- Mitral Valve Repair
- Aortic Valve Repair
- Complex Valve Repair Surgery
- Minimally Invasive Surgery
- Aortic Aneurysm
- Valve Replacement Surgery
- Heart Failure
- Ventricular Assist Device
- Heart Transplantation
- Lung Transplantation
- Heart-Lung Transplantation
- Coronary Artery Bypass
- Coronary Artery Bypass, Off-Pump
- Reoperative Cardiac Surgery
- Clinical Device Trials
- Thoracic and Cardiovascular Surgery
Associate Director, Stanford Cardiovascular Institute, CT Surgery (2014 - Present)
Member, Perioperative Services Medical Committee (2014 - Present)
Member, Executive Committee, Stanford University School of Medicine (2014 - Present)
Attending Cardiothoracic Surgeon, Lucille Packard Children’s Hospital (2014 - Present)
Attending Cardiothoracic Surgeon, Stanford Hospital and Clinics (2014 - Present)
Chair, Department of Cardiothoracic Surgery, Stanford University School of Medicine (2014 - Present)
Honors & Awards
Surgical Mentorship Teaching Award, Department of Surgery, University of Pennsylvania (2013)
Luigi Mastroianni Clinical Innovator Award, University of Pennsylvania (2012)
Top Doctors of Philadelphia Region, Philadelphia Magazine (2009, 2010, 2011, 2012, 2013)
Class of 2012 Teaching Award, Penn Medicine (2009)
10 Philadelphia Medical Researchers to Watch for 2005, Philadelphia Inquirer (2005)
21 Up and Coming Leaders of Philadelphia Award Winner, Philadelphia Magazine (2003)
40 under Forty Award Winner, Philadelphia Business Journal (2003)
Leonard J. Perloff Chief Resident Teaching Award (as determined by fellow residents), Department of Surgery, University of Pennsylvania (1999)
Resident Prize First Place, Pennsylvania Association of Thoracic Surgery (1997)
Surgical Scholar Award (Scoring 99th percentile on American Board of Surgery In-Service Exam), Department of Surgery, University of Pennsylvania (1997)
Vivien Thomas Young Investigator Award Winner, American Heart Association (1997)
William Y. Inouye Teaching Award (Top resident teacher as determined by medical students), Department of Surgery, University of Pennsylvania (1997)
Penn Pearls Teaching Award (Teaching excellence, as determined by medical students), University of Pennsylvania (1995)
I. S. Ravdin Prize (Top student in surgery), Department of Surgery, University of Pennsylvania (1992)
Alpha Omega Alpha, University of Pennsylvania (1991)
Boards, Advisory Committees, Professional Organizations
Chair, Leadership Committee, Council on Cardiovascular Surgery and Anesthesia, American Heart Association (2013 - Present)
Co-Director, American Association for Thoracic Surgery/NIH Grant Workshop (2013 - 2013)
Co-Chair, Research Scholarship Committee, American Association for Thoracic Surgery (2012 - 2014)
Member, Scientific Publishing Committee, American Heart Association (2012 - 2014)
Chair, Publications Committee, Society of University Surgeons (2012 - 2013)
Member, Society of Thoracic Surgeons Workforce for Research Development Taskforce on Grant Procurement (2011 - Present)
Vice-Chair, Leadership Committee, Council on Cardiovascular Surgery and Anesthesia, American Heart Association (2011 - 2013)
Member, Publications Committee, Association for Academic Surgery (2011 - 2012)
Co-Director, American Association for Thoracic Surgery/NIH Grant Workshop (2011 - 2011)
Member, Society of Clinical Surgery (2010 - Present)
Member, Research Scholarship Committee, American Association for Thoracic Surgery (2010 - 2014)
Chair, Scientific Sessions Program Committee, Council on Cardiovascular Surgery and Anesthesia, American Heart Association (2010 - 2012)
Liaison, Leadership Committee, Council on Functional Genomics and Translational Biology, American Heart Association (2010 - 2012)
Member, Cardiac Surgery Biology Club (2009 - Present)
Member, Program Committee, American College of Cardiology Annual Scientific Session (2009 - 2011)
Member, American Association for Thoracic Surgery (2007 - Present)
Member, Scientific Affairs and Government Relations Committee, American Association for Thoracic Surgery (2007 - Present)
Member, Research Committee, Thoracic Surgery Foundation for Research and Education (2007 - 2013)
Vice-Chair, Scientific Sessions Program Committee, Council on Cardiovascular Surgery and Anesthesia, American Heart Association (2007 - 2009)
Fellowship, F.A.H.A. (2006 - Present)
Member, Scientific Sessions Program Committee, Council on Cardiovascular Surgery and Anesthesia, American Heart Association (2006 - 2007)
Member, Society of University Surgeons (2005 - Present)
Member, Asian Society for Cardiovascular Surgery (2005 - Present)
Fellowship, F.A.C.C. (2004 - Present)
Fellowship, F.A.C.S. (2004 - Present)
Member, Leadership Committee, Council on Cardiovascular Surgery and Anesthesia, American Heart Association (2004 - Present)
Member, College of Physicians of Philadelphia (2003 - Present)
Member, American Heart Association, Council for Cardiothoracic and Vascular Surgery (2002 - Present)
Member, International Society for Minimally Invasive Cardiac Surgery (2002 - Present)
Member, International Society for Heart Research (2002 - Present)
Member, Association for Academic Surgery (2002 - Present)
Member, International Society for Heart & Lung Transplantation (2002 - Present)
Member, Society of Thoracic Surgeons (2002 - Present)
Medical Education:Perelman School of Medicine University of Pennsylvania (1992) PA
Fellowship:Hospital of the University of Pennsylvania Integrated Vascular Surgery Training (2001) PA
Board Certification: Thoracic and Cardiovascular Surgery, American Board of Thoracic Surgery (2002)
Board Certification: General Surgery, American Board of Surgery (2000)
Residency:Hospital of the University of Pennsylvania (1999) PA
Internship:Hospital of the University of Pennsylvania (1993) PA
Fellow, University of Pennsylvania, Cardiothoracic Surgery (2001)
Resident, University of Pennsylvania, Cardiothoracic Surgery (2001)
Chief Resident, University of Pennsylvania, Surgery (1999)
Post-Doctoral Research Fellow, University of Pennsylvania (1997)
Resident, University of Pennsylvania, Surgery (1998)
Intern, University of Pennsylvania, Surgery (1993)
MD, University of Pennsylvania School of Medicine (1992)
BS, Massachusetts Institute of Technology (1988)
Y. Joseph Woo, Pavan Atluri. "United States Patent 61/568,866 (Provisional Application Filed) Ventricular Assist Device Sleeve Adapter", Dec 9, 2011
Y. Joseph Woo, Howard C. Herrmann. "United States Patent 10/591,963 Device for Facilitating Antegrade Cardioplegia delivery in Patients with Aortic Insufficiency", Apr 19, 2011
Evaluating the Benefit of Concurrent Tricuspid Valve Repair During Mitral Surgery
The purpose of the research is to determine whether repairing a tricuspid valve (TV) in patients with mild to moderate tricuspid regurgitation (TR), at the time of planned mitral valve surgery (MVS), would improve the heart health of those who receive it compared to those who do not. At this point, the medical community is split in their opinion on whether surgeons should routinely repair mild to moderate TR in patients who are undergoing planned mitral valve surgery, and this study will answer this question.
Surgical Treatment of Aortic Stenosis With a Next Generation, Rapid Deployment Surgical Aortic Valve
The purpose of the clinical study is to prove that the heart valve device is safe, effective, and performs as intended.
Safety & Efficacy of Intramyocardial Injection of Mesenchymal Precursor Cells on Myocardial Function in LVAD Recipients
The main purpose of this research is to determine whether injecting mesenchymal precursor cells (MPC) into the heart during surgery to implant a left ventricular assist device (LVAD) is safe. MPCs are normally present in human bone marrow and have been shown to increase the development of blood vessels and new heart muscle cells in the heart. In addition, this research is being done to test whether injecting the MPCs into the heart is effective in improving heart function.
Stanford is currently not accepting patients for this trial. For more information, please contact Joseph Woo, MD, 650-725-3828.
Independent Studies (9)
- Bioengineering Problems and Experimental Investigation
BIOE 191 (Aut, Win, Spr, Sum)
- Directed Investigation
BIOE 392 (Aut, Win, Spr, Sum)
- Directed Reading in Cardiothoracic Surgery
CTS 299 (Win, Spr, Sum)
- Directed Study
BIOE 391 (Spr)
- Early Clinical Experience in Cardiothoracic Surgery
CTS 280 (Win, Spr, Sum)
- Engineering Problems
ME 391 (Win)
- Graduate Research
CTS 399 (Win, Spr, Sum)
- Medical Scholars Research
CTS 370 (Aut, Win, Spr, Sum)
- Undergraduate Research
CTS 199 (Win, Spr, Sum)
- Bioengineering Problems and Experimental Investigation
A novel protein-engineered hepatocyte growth factor analog released via a shear-thinning injectable hydrogel enhances post-infarction ventricular function.
Biotechnology and bioengineering
In the last decade, numerous growth factors and biomaterials have been explored for the treatment of myocardial infarction (MI). While pre-clinical studies have demonstrated promising results, clinical trials have been disappointing and inconsistent, likely due to poor translatability. In the present study, we investigate a potential myocardial regenerative therapy consisting of a protein-engineered dimeric fragment of hepatocyte growth factor (HGFdf) encapsulated in a shear-thinning, self-healing, bioengineered hydrogel (SHIELD). We hypothesized that SHIELD would facilitate targeted, sustained intramyocardial delivery of HGFdf thereby attenuating myocardial injury and post-infarction remodeling. Adult male Wistar rats (n = 45) underwent sham surgery or induction of MI followed by injection of phosphate buffered saline (PBS), 10 μg HGFdf alone, SHIELD alone, or SHIELD encapsulating 10 μg HGFdf. Ventricular function, infarct size, and angiogenic response were assessed 4 weeks post-infarction. Treatment with SHIELD + HGFdf significantly reduced infarct size and increased both ejection fraction and borderzone arteriole density compared to the controls. Thus, sustained delivery of HGFdf via SHIELD limits post-infarction adverse ventricular remodeling by increasing angiogenesis and reducing fibrosis. Encapsulation of HGFdf in SHIELD improves clinical translatability by enabling minimally-invasive delivery and subsequent retention and sustained administration of this novel, potent angiogenic protein analog. Biotechnol. Bioeng. 2017;9999: 1-11. © 2017 Wiley Periodicals, Inc.
View details for DOI 10.1002/bit.26345
View details for PubMedID 28574594
Pneumonia after cardiac surgery: Experience of the National Institutes of Health/Canadian Institutes of Health Research Cardiothoracic Surgical Trials Network.
journal of thoracic and cardiovascular surgery
2017; 153 (6): 1384-1391 e3
Pneumonia remains the most common major infection after cardiac surgery despite numerous preventive measures.To prospectively examine the timing, pathogens, and risk factors, including modifiable management practices, for postoperative pneumonia and estimate its impact on clinical outcomes.A total of 5158 adult cardiac surgery patients were enrolled prospectively in a cohort study across 10 centers. All infections were adjudicated by an independent committee. Competing risk models were used to assess the association of patient characteristics and management practices with pneumonia within 65 days of surgery. Mortality was assessed by Cox proportional hazards model and length of stay by a multistate model.The cumulative incidence of pneumonia was 2.4%, 33% of which occurred after discharge. Older age, lower hemoglobin level, chronic obstructive pulmonary disease, steroid use, operative time, and left ventricular assist device/heart transplant were risk factors. Ventilation time (24-48 vs ≤24 hours; hazard ratio [HR], 2.83; 95% confidence interval [95% CI], 1.72-4.66; >48 hours HR, 4.67; 95% CI, 2.70-8.08), nasogastric tubes (HR, 1.80; 95% CI, 1.10-2.94), and each unit of blood cells transfused (HR, 1.16; 95% CI, 1.08-1.26) increased the risk of pneumonia. Prophylactic use of second-generation cephalosporins (HR, 0.66; 95% CI, 0.45-0.97) and platelet transfusions (HR, 0.49, 95% CI, 0.30-0.79) were protective. Pneumonia was associated with a marked increase in mortality (HR, 8.89; 95% CI, 5.02-15.75) and longer length of stay of 13.55 ± 1.95 days (bootstrap 95% CI, 10.31-16.58).Pneumonia continues to impose a major impact on the health of patients after cardiac surgery. After we adjusted for baseline risk, several specific management practices were associated with pneumonia, which offer targets for quality improvement and further research.
View details for DOI 10.1016/j.jtcvs.2016.12.055
View details for PubMedID 28341473
Injectable Bioengineered Hydrogel Therapy in the Treatment of Ischemic Cardiomyopathy.
Current treatment options in cardiovascular medicine
2017; 19 (4): 30-?
Over the past two decades, the field of cardiovascular medicine has seen the rapid development of multiple different modalities for the treatment of ischemic myocardial disease. Most research efforts have focused on strategies aimed at coronary revascularization, with significant technological advances made in percutaneous coronary interventions as well as coronary artery bypass graft surgery. However, recent research efforts have shifted towards ways to address the downstream effects of myocardial infarction on both cellular and molecular levels. To this end, the broad application of injectable hydrogel therapy after myocardial infarction has stimulated tremendous interest. In this article, we will review what hydrogels are, how they can be bioengineered in unique ways to optimize therapeutic potential, and how they can be used as part of a treatment strategy after myocardial infarction.
View details for DOI 10.1007/s11936-017-0530-x
View details for PubMedID 28337717
- A modified implantation technique of left ventricular assist device: optimal outflow tract positioning. International journal of cardiology 2016; 223: 776-778
Regulating Stem Cell Secretome Using Injectable Hydrogels with In Situ Network Formation.
Advanced healthcare materials
A family of shear-thinning hydrogels for injectable encapsulation and long-term delivery (SHIELD) has been designed and synthesized with controlled in situ stiffening properties to regulate the stem cell secretome. The authors demonstrate that SHIELD with an intermediate stiffness (200-400 Pa) could significantly promote the angiogenic potential of human adipose-derived stem cells.
View details for DOI 10.1002/adhm.201600497
View details for PubMedID 27709809
Biochemically engineered stromal cell-derived factor 1-alpha analog increases perfusion in the ischemic hind limb.
Journal of vascular surgery
2016; 64 (4): 1093-1099
Despite promising therapeutic innovation over the last decade, peripheral arterial disease remains a prevalent morbidity, as many patients are still challenged with peripheral ischemia. We hypothesized that delivery of engineered stromal cell-derived factor 1-alpha (ESA) in an ischemic hind limb will yield significant improvement in perfusion.Male rats underwent right femoral artery ligation, and animals were randomized to receive a 100 μL injection of saline (n = 9) or 6 μg/kg dosage of equal volume of ESA (n = 12) into the ipsilateral quadriceps muscle. Both groups of animals were also given an intraperitoneal injection of 40 μg/kg of granulocyte macrophage colony-stimulating factor (GMCSF). Perfusion was quantified using a laser Doppler imaging device preoperatively, and on postoperative days 0, 7, and 14. Immunohistochemistry was performed to quantify angiogenesis on day 14, and an mRNA profile was evaluated for angiogenic and inflammatory markers.Compared with the saline/GMCSF group at day 14, the ESA/GMCSF-injected animals had greater reperfusion ratios (Saline/GMCSF, 0.600 ± 0.140 vs ESA/GMCSF, 0.900 ± 0.181; group effect P = .006; time effect P < .0001; group×time effect P < .0001), elevated capillary density (10×; Saline/GMCSF, 6.40 ± 2.01 vs ESA/GMCSF, 18.55 ± 5.30; P < .01), and increased mRNA levels of vascular endothelial growth factor-A (Saline/GMCSF [n = 6], 0.298 ± 0.205 vs ESA/GMCSF [n = 8], 0.456 ± 0.139; P = .03).Delivery of ESA significantly improves perfusion in a rat model of peripheral arterial disease via improved neovasculogenesis, a finding which may prove beneficial in the treatment strategy for this debilitating disease.
View details for DOI 10.1016/j.jvs.2015.06.140
View details for PubMedID 26372192
The value of preoperative 3-dimensional over 2-dimensional valve analysis in predicting recurrent ischemic mitral regurgitation after mitral annuloplasty.
journal of thoracic and cardiovascular surgery
2016; 152 (3): 847-859
Repair for ischemic mitral regurgitation with undersized annuloplasty is characterized by high recurrence rates. We sought to determine the value of pre-repair 3-dimensional echocardiography over 2-dimensional echocardiography in predicting recurrence at 6 months.Intraoperative transesophageal 2-dimensional echocardiography and 3-dimensional echocardiography were performed in 50 patients undergoing undersized annuloplasty for ischemic mitral regurgitation. Two-dimensional echocardiography annular diameter and tethering parameters were measured in the apical 2- and 4-chamber views. A customized protocol was used to assess 3-dimensional annular geometry and regional leaflet tethering. Recurrence (grade ≥2) was assessed with 2-dimensional transthoracic echocardiography at 6 months.Preoperative 2- and 3-dimensional annular geometry were similar in all patients with ischemic mitral regurgitation. Preoperative 2- and 3-dimensional leaflet tethering were significantly higher in patients with recurrence (n = 13) when compared with patients without recurrence (n = 37). Multivariate logistic regression revealed preoperative 2-dimensional echocardiography posterior tethering angle as an independent predictor of recurrence with an optimal cutoff value of 32.0° (area under the curve, 0.81; 95% confidence interval, 0.68-0.95; P = .002) and preoperative 3-dimensional echocardiography P3 tethering angle as an independent predictor of recurrence with an optimal cutoff value of 29.9° (area under the curve, 0.92; 95% confidence interval, 0.84-1.00; P < .001). The predictive value of the 3-dimensional geometric multivariate model can be augmented by adding basal aneurysm/dyskinesis (area under the curve, 0.94; 95% confidence interval, 0.87-1.00; P < .001).Preoperative 3-dimensional echocardiography P3 tethering angle is a stronger predictor of ischemic mitral regurgitation recurrence after annuloplasty than preoperative 2-dimensional echocardiography posterior tethering angle, which is highly influenced by viewing plane. In patients with a preoperative P3 tethering angle of 29.9° or larger (especially when combined with basal aneurysm/dyskinesis), chordal-sparing valve replacement should be strongly considered.
View details for DOI 10.1016/j.jtcvs.2016.06.040
View details for PubMedID 27530639
Modeling the Myxomatous Mitral Valve With Three-Dimensional Echocardiography.
Annals of thoracic surgery
2016; 102 (3): 703-710
Degenerative mitral valve disease is associated with variable and complex defects in valve morphology. Three-dimensional echocardiography (3DE) has shown promise in aiding preoperative planning for patients with this disease but to date has not been as transformative as initially predicted. The clinical usefulness of 3DE has been limited by the laborious methods currently required to extract quantitative data from the images.To maximize the utility of 3DE for preoperative valve evaluation, this work describes an automated 3DE image analysis method for generating models of the mitral valve that are well suited for both qualitative and quantitative assessment. The method is unique in that it captures detailed alterations in mitral leaflet and annular morphology and produces image-derived models with locally varying leaflet thickness. The method is evaluated on midsystolic transesophageal 3DE images acquired from 22 subjects with myxomatous degeneration and from 22 subjects with normal mitral valve morphology.Relative to manual image analysis, the automated method accurately represents both normal and complex leaflet geometries with a mean boundary displacement error on the order of one image voxel. A detailed quantitative analysis of the valves is presented and reveals statistically significant differences between normal and myxomatous valves with respect to numerous aspects of annular and leaflet geometry.This work demonstrates a successful methodology for the relatively rapid quantitative description of the complex mitral valve distortions associated with myxomatous degeneration. The methodology has the potential to significantly improve surgical planning for patients with complex mitral valve disease.
View details for DOI 10.1016/j.athoracsur.2016.05.087
View details for PubMedID 27492671
- Novel MRI Contrast Agent from Magnetotactic Bacteria Enables In Vivo Tracking of iPSC-derived Cardiomyocytes SCIENTIFIC REPORTS 2016; 6
Influence of durable mechanical circulatory support and allosensitization on mortality after heart transplantation.
journal of heart and lung transplantation
2016; 35 (6): 731-742
Allosensitization has been shown to negatively affect post-heart transplant (HTx) survival even with a negative crossmatch. Whether allosensitization related to mechanical circulatory support (MCS) is associated with worse post-HTx survival remains controversial.Adult HTx recipients listed in the United Network for Organ Sharing database (July 2006-December 2012) were identified. Multivariate Cox regression assessed the effect of allosensitization on survival. Propensity matching was performed to compare patients who were and were not allosensitized. Kaplan-Meier survival analysis compared matched and unmatched patients in the MCS and medically managed cohorts.We identified 11,840 HTx recipients, of whom 4,167 had MCS. MCS was associated with allosensitization in multivariate logistic regression. Each different MCS device was associated with worse post-HTx survival in multivariate Cox regression. Allosensitization did not predict post-HTx mortality in MCS patients (hazard ratio, 1.07; 95% confidence interval, 0.89-1.28; p = 0.48. Among patients without MCS, allosensitization was associated with post-HTx mortality (hazard ratio, 1.19; 95% confidence interval, 1.03-1.39; p = 0.02). Kaplan-Meier analysis revealed equivalent survival in unmatched and matched cohorts when MCS patients who were allosensitized were compared with non-allosensitized MCS patients. Among non-MCS patients, allosensitization was associated with worse survival in unmatched and matched analysis.MCS was associated with allosensitization. For MCS patients, allosensitization did not independently predict worse post-HTx outcome. Among non-MCS patients, allosensitization was associated with worse post-HTx survival. Allosensitization appears to be a heterogeneous process influenced by presence of MCS.
View details for DOI 10.1016/j.healun.2015.12.023
View details for PubMedID 26856669
Treatment and Prognosis of Pulmonary Hypertension in the Left Ventricular Assist Device Patient.
Current heart failure reports
2016; 13 (3): 140-150
This review will discuss the medical management of pulmonary hypertension in patients with left ventricular assist devices. Although much has been written on the management of primary pulmonary hypertension, also called pulmonary arterial hypertension, this review will instead focus on the treatment of pulmonary hypertension secondary to left heart disease. The relevant pharmacotherapy can be divided into medications for treating heart failure, such as diuretics and β-blockers, and medications for treating pulmonary hypertension. We also discuss important preoperative considerations in patients with pulmonary hypertension; the relationships between left ventricular assist devices, pulmonary hemodynamics, and right heart failure; as well as optimal perioperative and long-term postoperative medical management of pulmonary hypertension.
View details for DOI 10.1007/s11897-016-0288-6
View details for PubMedID 27241336
- Influence of durable mechanical circulatory support and allosensitization on mortality after heart transplantation JOURNAL OF HEART AND LUNG TRANSPLANTATION 2016; 35 (6): 731-742
- 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS 2016; 87 (6): 1001-1019
Isolation and trans-differentiation of mesenchymal stromal cells into smooth muscle cells: Utility and applicability for cell-sheet engineering.
2016; 18 (4): 510-517
Bone marrow (BM)-derived mesenchymal stromal cells (MSCs) have shown potential to differentiate into various cell types, including smooth muscle cells (SMCs). The extracellular matrix (ECM) represents an appealing and readily available source of SMCs for use in tissue engineering. In this study, we hypothesized that the ECM could be used to induce MSC differentiation to SMCs for engineered cell-sheet construction.Primary MSCs were isolated from the BM of Wistar rats, transferred and cultured on dishes coated with 3 different types of ECM: collagen type IV (Col IV), fibronectin (FN), and laminin (LM). Primary MSCs were also included as a control. The proportions of SMC (a smooth muscle actin [aSMA] and SM22a) and MSC markers were examined with flow cytometry and Western blotting, and cell proliferation rates were also quantified.Both FN and LM groups were able to induce differentiation of MSCs toward smooth muscle-like cell types, as evidenced by an increase in the proportion of SMC markers (aSMA; Col IV 42.3 ± 6.9%, FN 65.1 ± 6.5%, LM 59.3 ± 7.0%, Control 39.9 ± 3.1%; P = 0.02, SM22; Col IV 56.0 ± 7.7%, FN 74.2 ± 6.7%, LM 60.4 ± 8.7%, Control 44.9 ± 3.6%) and a decrease in that of MSC markers (CD105: Col IV 64.0 ± 5.2%, FN 57.6 ± 4.0%, LM 60.3 ± 7.0%, Control 85.3 ± 4.2%; P = 0.03). The LM group showed a decrease in overall cell proliferation, whereas FN and Col IV groups remained similar to control MSCs (Col IV, 9.0 ± 2.3%; FN, 9.8 ± 2.5%; LM, 4.3 ± 1.3%; Control, 9.8 ± 2.8%).Our findings indicate that ECM selection can guide differentiation of MSCs into the SMC lineage. Fibronectin preserved cellular proliferative capacity while yielding the highest proportion of differentiated SMCs, suggesting that FN-coated materials may be facilitate smooth muscle tissue engineering.
View details for DOI 10.1016/j.jcyt.2016.01.012
View details for PubMedID 26971679
- 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. Circulation 2016; 133 (11): 1135-1147
- 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction: An Update of the 2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention and the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. Journal of the American College of Cardiology 2016; 67 (10): 1235-1250
Stem cell-based therapies to promote angiogenesis in ischemic cardiovascular disease
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
2016; 310 (4): H455-H465
Stem cell therapy is a promising approach for treatment of tissue ischemia associated with myocardial infarction and peripheral arterial disease. Stem and progenitor cells derived from bone marrow or from pluripotent stem cells have shown therapeutic benefit in boosting angiogenesis as well as restoring tissue function. Notably, adult stem and progenitor cells including mononuclear cells, endothelial progenitor cells, and mesenchymal stem cells have progressed into clinical trials and have shown positive benefits. In this review, we overview the major classes of stem and progenitor cells, including pluripotent stem cells, and summarize the state-of-the-art in applying these cell types for treating myocardial infarction and peripheral arterial disease.
View details for DOI 10.1152/ajpheart.00726.2015
View details for Web of Science ID 000370191000001
View details for PubMedID 26683902
- Preoperative Three-Dimensional Valve Analysis Predicts Recurrent Ischemic Mitral Regurgitation After Mitral Annuloplasty ANNALS OF THORACIC SURGERY 2016; 101 (2): 567-575
Novel MRI Contrast Agent from Magnetotactic Bacteria Enables In Vivo Tracking of iPSC-derived Cardiomyocytes.
2016; 6: 26960-?
Therapeutic delivery of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (iCMs) represents a novel clinical approach to regenerate the injured myocardium. However, methods for robust and accurate in vivo monitoring of the iCMs are still lacking. Although superparamagnetic iron oxide nanoparticles (SPIOs) are recognized as a promising tool for in vivo tracking of stem cells using magnetic resonance imaging (MRI), their signal persists in the heart even weeks after the disappearance of the injected cells. This limitation highlights the inability of SPIOs to distinguish stem cell viability. In order to overcome this shortcoming, we demonstrate the use of a living contrast agent, magneto-endosymbionts (MEs) derived from magnetotactic bacteria for the labeling of iCMs. The ME-labeled iCMs were injected into the infarcted area of murine heart and probed by MRI and bioluminescence imaging (BLI). Our findings demonstrate that the MEs are robust and effective biological contrast agents to track iCMs in an in vivo murine model. We show that the MEs clear within one week of cell death whereas the SPIOs remain over 2 weeks after cell death. These findings will accelerate the clinical translation of in vivo MRI monitoring of transplanted stem cell at high spatial resolution and sensitivity.
View details for DOI 10.1038/srep26960
View details for PubMedID 27264636
View details for PubMedCentralID PMC4893600
- Midterm Outcomes of Open Descending Thoracic Aortic Repair in More Than 5,000 Medicare Patients ANNALS OF THORACIC SURGERY 2015; 100 (6): 2087-2094
- A Tissue-Engineered Chondrocyte Cell Sheet Induces Extracellular Matrix Modification to Enhance Ventricular Biomechanics and Attenuate Myocardial Stiffness in Ischemic Cardiomyopathy TISSUE ENGINEERING PART A 2015; 21 (19-20): 2515-2525
Evaluation of late aortic insufficiency with continuous flow left ventricular assist device†.
European journal of cardio-thoracic surgery
2015; 48 (3): 400-406
The aim of this study was to evaluate late development of aortic insufficiency (AI) with continuous flow left ventricular assist device (CLVAD). Development of AI is an increasingly recognized important complication in CLVAD therapy, but there are still few reports about this topic.We analysed data from 99 patients who underwent CLVAD implantation. De novo AI was defined as the development of mild or greater AI in patients with none or trace preoperative AI. Anatomic and functional correlates of de novo AI were investigated.Among the 17 patients with preoperative mild AI, no improvements were observed in mitral regurgitation or LV end-systolic dimension. Of the remaining 82 patients, de novo AI was identified in 43 patients (52%), on the most recent follow-up echocardiography, and did not influence survival nor improvement of LV geometry. Rate of freedom from de novo AI at 1 year after CLVAD implantation was 35.9%. Development of significantly greater AI was observed in patients without valve opening (AI grade 1.3 ± 1.0 vs 0.7 ± 0.9; P = 0.005). By multivariate Cox hazard model, smaller body surface area (BSA) [hazard ratio: 0.83 [95% confidence interval (CI): 0.72-0.97], P = 0.018], larger aortic root diameter (AOD) [hazard ratio: 1.11 (95% CI: 1.02-1.22), P = 0.012] and higher pulmonary artery systolic pressure (PASP) [hazard ratio: 1.24 (95% CI: 1.10-1.41), P < 0.001] were identified as the independent preoperative risk factors for de novo AI. In a subset of patients with speed adjustments, increase of CLVAD speed worsened AI and led to insufficient LV unloading in patients with aortic dilatation (AOD ≥ 3.5 cm).Any significant mortality difference related to preoperative or development of postimplant AI was not found. AI was associated with changes in LV size, and there appears to be an interaction between BSA, preoperative PASP, time since implant, aortic valve opening, aortic size and development of AI. Longitudinal clinical management in CLVAD patients, particularly in terms of CLVAD speed optimization, should include careful assessment.
View details for DOI 10.1093/ejcts/ezu507
View details for PubMedID 25653250
Alternative approaches for mitral valve repair.
Annals of cardiothoracic surgery
2015; 4 (5): 469-473
Unique situations arise in which alternative exposures for mitral valve surgery offer distinct advantages over traditional approaches. Each exposure facilitates both mitral valve repair and replacement, although the standard repair procedures must be modified to accommodate these non-traditional exposures. Here, we detail the technical considerations required to perform transventricular and transaortic mitral valve repair as well as discuss the advantages for employing these less conventional approaches.
View details for DOI 10.3978/j.issn.2225-319X.2015.08.10
View details for PubMedID 26539353
View details for PubMedCentralID PMC4598473
Prior Sternotomy and Ventricular Assist Device Implantation Do Not Adversely Impact Survival or Allograft Function After Heart Transplantation
ANNALS OF THORACIC SURGERY
2015; 100 (2): 542-549
Orthotopic heart transplantation (OHT) remains the gold standard for end-stage heart failure. However, donor availability is severely limited. With a median wait time of 6.6 months and more than 12% of patients waiting 5 or more years, the decision is often made to implant a left ventricular assist device (LVAD) as a bridge to transplantation for medical stabilization. Furthermore, the number of patients who have had at least one prior sternotomy while awaiting transplantation is increasing. Previous studies have indicated reoperative sternotomy as a risk factor for compromised survival. Concerns are specifically focused on perioperative, short-term, and long-term outcomes after LVAD explantation or redo sternotomy before OHT because of increasing operative complexity. We hypothesize that despite the greater technical difficulty caused by LVAD explantation or redo sternotomy, outcomes would not be compromised.We retrospectively analyzed patients who underwent OHT at the University of Pennsylvania during a 5-year period (2008-2013; n = 253). All patients who underwent a bridge to transplantation LVAD (n = 72) or prior sternotomy (n = 65) were compared with those undergoing OHT with a virgin chest (n = 116). Preoperative, intraoperative, and postoperative variables were analyzed. Short- and long-term survival were studied (minimum follow-up, 6 months).Comorbidities were similar among the groups. There was no difference in donor allograft ischemic time (p = 0.6). However, cardiopulmonary bypass time was longer in both bridge to transplantation and prior sternotomy cohorts (p < 0.00001). The blood transfusion requirement was higher in bridge to transplantation (12.5 ± 13.7 units; p = 0.0007) and prior sternotomy groups (11.7 ± 12.9 units; p = 0.02) as compared with the virgin chest cohort (7.1 ± 10.7 units). For bridge to transplantation, both time to extubation (1.0 ± 1.6 versus 0.9 ± 1.0 days; p = 0.03) and intensive care unit length of stay (7.0 ± 7.0 versus 6.0 ± 7.0 days; p = 0.06) were longer compared with the virgin chest cohort. The same was true for prior sternotomy (extubation time, 1.9 ± 4.4 days; p = 0.005; intensive care unit length of stay, 8.0 ± 12.0 days; p = 0.06). There was no difference in hospital length of stay (p = 0.2). Overall, there was no difference in short- or long-term survival.Implantation of an LVAD as a bridge to transplantation or prior sternotomy does not adversely impact allograft function, hospital length of stay, or long-term outcomes after OHT. The decision to manage a patient medically while awaiting transplantation versus an LVAD bridge strategy should not be limited by concerns of subsequent poor outcomes after transplantation.
View details for DOI 10.1016/j.athoracsur.2015.02.093
View details for Web of Science ID 000358798200035
View details for PubMedID 26070597
Aligned-Braided Nanofibrillar Scaffold with Endothelial Cells Enhances Arteriogenesis.
2015; 9 (7): 6900-6908
The objective of this study was to enhance the angiogenic capacity of endothelial cells (ECs) using nanoscale signaling cues from aligned nanofibrillar scaffolds in the setting of tissue ischemia. Thread-like nanofibrillar scaffolds with porous structure were fabricated from aligned-braided membranes generated under shear from liquid crystal collagen solution. Human ECs showed greater outgrowth from aligned scaffolds than from nonpatterned scaffolds. Integrin α1 was in part responsible for the enhanced cellular outgrowth on aligned nanofibrillar scaffolds, as the effect was abrogated by integrin α1 inhibition. To test the efficacy of EC-seeded aligned nanofibrillar scaffolds in improving neovascularization in vivo, the ischemic limbs of mice were treated with EC-seeded aligned nanofibrillar scaffold; EC-seeded nonpatterned scaffold; ECs in saline; aligned nanofibrillar scaffold alone; or no treatment. After 14 days, laser Doppler blood spectroscopy demonstrated significant improvement in blood perfusion recovery when treated with EC-seeded aligned nanofibrillar scaffolds, in comparison to ECs in saline or no treatment. In ischemic hindlimbs treated with scaffolds seeded with human ECs derived from induced pluripotent stem cells (iPSC-ECs), single-walled carbon nanotube (SWNT) fluorophores were systemically delivered to quantify microvascular density after 28 days. Near infrared-II (NIR-II, 1000-1700 nm) imaging of SWNT fluorophores demonstrated that iPSC-EC-seeded aligned scaffolds group showed significantly higher microvascular density than the saline or cells groups. These data suggest that treatment with EC-seeded aligned nanofibrillar scaffolds improved blood perfusion and arteriogenesis, when compared to treatment with cells alone or scaffold alone, and have important implications in the design of therapeutic cell delivery strategies.
View details for DOI 10.1021/acsnano.5b00545
View details for PubMedID 26061869
- Protein Corona Influences Cell-Biomaterial Interactions in Nanostructured Tissue Engineering Scaffolds ADVANCED FUNCTIONAL MATERIALS 2015; 25 (28): 4379-4389
- Aligned-Braided Nanofibrillar Scaffold with Endothelial Cells Enhances Arteriogenesis ACS NANO 2015; 9 (7): 6900-6908
A "Repair-All" Strategy for Degenerative Mitral Valve Disease Safely Minimizes Unnecessary Replacement.
Annals of thoracic surgery
2015; 99 (6): 1983-1990
We examined the feasibility and efficacy of a "repair-all" strategy applied in all patients with degenerative mitral regurgitation, regardless of valve complexity, risk profile, and surgical approach.Between 2002 and 2011, 4,241 patients underwent mitral operations at our institution. Analysis was limited to 525 consecutive patients with mitral regurgitation due to leaflet prolapse (posterior, 75%; anterior, 5%; bileaflet, 20%) who underwent isolated mitral operations. A right minithoracotomy was used in 46% of procedures. Propensity scores identified 153 well-matched patient pairs for evaluation of the effect of surgical approach on valve reparability.Mitral repair was successful in 99% (520 of 525) of patients. The location of the leaflet prolapse did not significantly influence the repair rate or the need for intraoperative revision of the initial repair. The repair rate and the need for intraoperative repair revision also did not significantly differ by surgical approach. Intraoperative revision did not confer a greater risk of perioperative morbidity or longer length of stay. At 8 years, freedom from severe mitral regurgitation was 97% ± 2%. Development of residual mitral regurgitation did not differ by location of the leaflet prolapse, need for repair revision, or surgical approach. After discharge, the survival trend did not differ between patients who did and did not require intraoperative repair revision.In experienced centers, a "repair-all" strategy for degenerative mitral regurgitation can be used with nearly 100% repair rates and excellent outcomes, regardless of valve complexity. When necessary, intraoperative revision of the initial repair may be performed in most patients without a significant incremental risk, thereby further enhancing repair rates.
View details for DOI 10.1016/j.athoracsur.2014.12.076
View details for PubMedID 25865766
- A "Repair-All" Strategy for Degenerative Mitral Valve Disease Safely Minimizes Unnecessary Replacement ANNALS OF THORACIC SURGERY 2015; 99 (6): 1983-1991
Early surgical intervention or watchful waiting for the management of asymptomatic mitral regurgitation: a systematic review and meta-analysis.
Annals of cardiothoracic surgery
2015; 4 (3): 220-229
Discordance between studies drives continued debate regarding the best management of asymptomatic severe mitral regurgitation (MR). The aim of the present study was to conduct a systematic review and meta-analysis of management plans for asymptomatic severe MR, and compare the effectiveness of a strategy of early surgery to watchful waiting.A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Studies were excluded if they: (I) lacked a watchful waiting cohort; (II) included symptomatic patients; or (III) included etiologies other than degenerative mitral valve disease. The primary outcome of the study was all-cause mortality at 10 years. Secondary outcomes included operative mortality, repair rate, repeat mitral valve surgery, and development of new atrial fibrillation.Five observational studies were eligible for review and three were included in the pooled analysis. In asymptomatic patients without class I triggers (symptoms or ventricular dysfunction), pooled analysis revealed a significant reduction in long-term mortality with an early surgery approach [hazard ratio (HR) =0.38; 95% confidence interval (CI): 0.21-0.71]. This survival benefit persisted in a sub-group analysis limited to patients without class II triggers (atrial fibrillation or pulmonary hypertension) [relative risk (RR) =0.85; 95% CI: 0.75-0.98]. Aggregate rates of operative mortality did not differ between treatment arms (0.7% vs. 0.7% for early surgery vs. watchful waiting). However, significantly higher repair rates were achieved in the early surgery cohorts (RR =1.10; 95% CI: 1.02-1.18).Despite disagreement between individual studies, the present meta-analysis demonstrates that a strategy of early surgery may improve survival and increase the likelihood of mitral valve repair compared with watchful waiting. Early surgery may also benefit patients when instituted prior to the development of class II triggers.
View details for DOI 10.3978/j.issn.2225-319X.2015.04.01
View details for PubMedID 26309823
View details for PubMedCentralID PMC4533073
Radical Resection of Cardiac Angiosarcoma with Atrioventricular Reconstruction
JOURNAL OF HEART VALVE DISEASE
2015; 24 (3): 379-382
View details for Web of Science ID 000369045600023
- Reply: To PMID 25069688. Annals of thoracic surgery 2015; 99 (4): 1489-?
Transaortic Aortomitral Junction Reconstruction and Mitral Valve Leaflet Repair for Recurrent Endocarditis
JOURNAL OF HEART VALVE DISEASE
2015; 24 (2): 173-176
Transaortic interventions on the mitral valve are rarely performed, but offer advantages over traditional approaches in certain circumstances, including either extensive involvement of the aortomitral junction with endocarditis or the patient requiring reoperation for aortic and mitral disease. Herein is presented a case of recurrent endocarditis involving aortomitral continuity, reconstructed using a transaortic mitral valve repair and reconstruction of the aortic and mitral annuli with a pericardial patch, followed by aortic root replacement.
View details for Web of Science ID 000369045500006
View details for PubMedID 26204680
- Shear-Thinning Supramolecular Hydrogels with Secondary Autonomous Covalent Crosslinking to Modulate Viscoelastic Properties In Vivo ADVANCED FUNCTIONAL MATERIALS 2015; 25 (4): 636-644
Natural history of coexistent tricuspid regurgitation in patients with degenerative mitral valve disease: Implications for future guidelines
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2014; 148 (6): 2802-2809
The management of coexistent tricuspid regurgitation in patients with mitral regurgitation remains controversial. We sought to define the incidence and natural history of coexistent tricuspid regurgitation in patients undergoing isolated mitral surgery for degenerative mitral regurgitation, as well as the effect of late secondary tricuspid regurgitation on cardiovascular symptom burden and survival.To minimize confounding, analysis was limited to 495 consecutive patients who underwent isolated mitral surgery for degenerative mitral valve disease between 2002 and 2011. Patients with coexistent severe tricuspid regurgitation were excluded because such patients typically undergo concomitant tricuspid intervention.Grade 1 to 3 coexistent tricuspid regurgitation was present in 215 patients (43%) preoperatively. Actuarial freedom from grade 3 to 4 tricuspid regurgitation 1, 5, and 9 years after surgery was 100% ± 0%, 90% ± 2%, and 64% ± 7%, respectively. Older age (P < .001) and grade of preoperative tricuspid regurgitation (P = .006) independently predicted postoperative progression of tricuspid regurgitation on multivariable analysis. However, when limited to patients with mild or absent tricuspid regurgitation, indexed tricuspid annular diameter was the only significant risk factor for late tricuspid regurgitation (P = .04). New York Heart Association functional class and long-term survival did not worsen with development of late secondary tricuspid regurgitation (P = .4 and P = .6, respectively). However, right ventricular dysfunction was significantly more common in patients with more severe late tricuspid regurgitation (P = .007).Despite durable correction of degenerative mitral regurgitation, less than severe tricuspid regurgitation is likely to progress after surgery if uncorrected. Given the low incremental risk of tricuspid annuloplasty, a more aggressive strategy of concomitant tricuspid repair may be warranted.
View details for DOI 10.1016/j.jtcvs.2014.08.001
View details for Web of Science ID 000345686100079
View details for PubMedID 25218532
Ventricular assist device implantation in the elderly.
Annals of cardiothoracic surgery
2014; 3 (6): 570-572
Dramatic advances in ventricular assist device (VAD) design and patient management have made mechanical circulatory support an attractive therapeutic option for the growing pool of elderly heart failure patients.A literature review of all relevant studies was performed. No time or language restrictions were imposed, and references of the selected studies were checked for additional relevant citations.In concordance with the universal trend in mechanical circulatory support, continuous flow devices appear to have particular benefits in the elderly. In addition, the literature suggests that early intervention before the development of cardiogenic shock, important in all patients, is particularly paramount in older patients.The ongoing refinement of patient selection, surgical technique, and post-operative care will continue to improve surgical outcomes, and absolute age may become a less pivotal criterion for mechanical circulatory support. However, clear guidelines for the use of mechanical circulatory support in the elderly remain undefined.
View details for DOI 10.3978/j.issn.2225-319X.2014.09.07
View details for PubMedID 25512896
Tissue-engineered, hydrogel-based endothelial progenitor cell therapy robustly revascularizes ischemic myocardium and preserves ventricular function.
journal of thoracic and cardiovascular surgery
2014; 148 (3): 1090-1098
Cell-based angiogenic therapy for ischemic heart failure has had limited clinical impact, likely related to low cell retention (<1%) and dispersion. We developed a novel, tissue-engineered, hydrogel-based cell-delivery strategy to overcome these limitations and provide prolonged regional retention of myocardial endothelial progenitor cells at high cell dosage.Endothelial progenitor cells were isolated from Wistar rats and encapsulated in fibrin gels. In vitro viability was quantified using a fluorescent live-dead stain of transgenic enhanced green fluorescent protein(+) endothelial progenitor cells. Endothelial progenitor cell-laden constructs were implanted onto ischemic rat myocardium in a model of acute myocardial infarction (left anterior descending ligation) for 4 weeks. Intramyocardial cell injection (2 × 10(6) endothelial progenitor cells), empty fibrin, and isolated left anterior descending ligation groups served as controls. Hemodynamics were quantified using echocardiography, Doppler flow analysis, and intraventricular pressure-volume analysis. Vasculogenesis and ventricular geometry were quantified. Endothelial progenitor cell migration was analyzed by using endothelial progenitor cells from transgenic enhanced green fluorescent protein(+) rodents.Endothelial progenitor cells demonstrated an overall 88.7% viability for all matrix and cell conditions investigated after 48 hours. Histologic assessment of 1-week implants demonstrated significant migration of transgenic enhanced green fluorescent protein(+) endothelial progenitor cells from the fibrin matrix to the infarcted myocardium compared with intramyocardial cell injection (28 ± 12.3 cells/high power field vs 2.4 ± 2.1 cells/high power field, P = .0001). We also observed a marked increase in vasculogenesis at the implant site. Significant improvements in ventricular hemodynamics and geometry were present after endothelial progenitor cell-hydrogel therapy compared with control.We present a tissue-engineered, hydrogel-based endothelial progenitor cell-mediated therapy to enhance cell delivery, cell retention, vasculogenesis, and preservation of myocardial structure and function.
View details for DOI 10.1016/j.jtcvs.2014.06.038
View details for PubMedID 25129603
Combined heart and liver transplantation can be safely performed with excellent short- and long-term results.
Annals of thoracic surgery
2014; 98 (3): 858-862
Heart transplant has become the gold standard therapy for end-stage heart failure. Short- and long-term outcomes after orthotopic heart transplant have been excellent. Many patients with heart failure manifest hepatic failure as a result of a chronically elevated central venous pressure. Concomitant hepatic failure has been a contraindication to heart transplant in most centers. A few select institutions are currently performing combined heart-liver transplantation to treat dual organ failure. The outcomes after dual organ transplant are largely unknown, with limited data from a few select centers. We undertook this study to analyze our large experience with combined heart-liver transplant and determine the short-term and long-term outcomes associated with this procedure.We have performed 1,050 heart transplants at our center to date. Of these patients, 26 underwent combined heart and liver transplant (largest single-center experience). We reviewed demographic, perioperative, and short- and long-term outcomes after this combined procedure.All 26 patients underwent successful dual organ transplant, without any episodes of primary graft dysfunction. Average length of intensive care unit stay was 10 ± 5 days, and average hospital stay was 25 ± 11 days. Kaplan-Meier analysis demonstrated excellent short-term survival (1 year, 87% ± 7%) and long-term survival (5 years, 83% ± 8%). Interestingly, only 3 patients (11%) demonstrated any evidence of rejection long-term by myocardial biopsy, suggesting that concomitant hepatic transplantation may provide immunologic protection for the cardiac allograft.We present the largest single-center series of combined heart and liver transplant. This dual organ strategy is highly feasible, with excellent long-term survival. Concomitant liver transplant may confer immunologic protection for the cardiac allograft.
View details for DOI 10.1016/j.athoracsur.2014.04.100
View details for PubMedID 25069688
- Bioengineered Stromal Cell- Derived Factor-1 alpha Analogue Delivered as an Angiogenic Therapy Significantly Restores Viscoelastic Material Properties of Infarcted Cardiac Muscle JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME 2014; 136 (8)
A bioengineered hydrogel system enables targeted and sustained intramyocardial delivery of neuregulin, activating the cardiomyocyte cell cycle and enhancing ventricular function in a murine model of ischemic cardiomyopathy.
Circulation. Heart failure
2014; 7 (4): 619-626
Neuregulin-1β (NRG) is a member of the epidermal growth factor family possessing a critical role in cardiomyocyte development and proliferation. Systemic administration of NRG demonstrated efficacy in cardiomyopathy animal models, leading to clinical trials using daily NRG infusions. This approach is hindered by requiring daily infusions and off-target exposure. Therefore, this study aimed to encapsulate NRG in a hydrogel to be directly delivered to the myocardium, accomplishing sustained localized NRG delivery.NRG was encapsulated in hydrogel, and release over 14 days was confirmed by ELISA in vitro. Sprague-Dawley rats were used for cardiomyocyte isolation. Cells were stimulated by PBS, NRG, hydrogel, or NRG-hydrogel (NRG-HG) and evaluated for proliferation. Cardiomyocytes demonstrated EdU (5-ethynyl-2'-deoxyuridine) and phosphorylated histone H3 positivity in the NRG-HG group only. For in vivo studies, 2-month-old mice (n=60) underwent left anterior descending coronary artery ligation and were randomized to the 4 treatment groups mentioned. Only NRG-HG-treated mice demonstrated phosphorylated histone H3 and Ki67 positivity along with decreased caspase-3 activity compared with all controls. NRG was detected in myocardium 6 days after injection without evidence of off-target exposure in NRG-HG animals. At 2 weeks, the NRG-HG group exhibited enhanced left ventricular ejection fraction, decreased left ventricular area, and augmented borderzone thickness.Targeted and sustained delivery of NRG directly to the myocardial borderzone augments cardiomyocyte mitotic activity, decreases apoptosis, and greatly enhances left ventricular function in a model of ischemic cardiomyopathy. This novel approach to NRG administration avoids off-target exposure and represents a clinically translatable strategy in myocardial regenerative therapeutics.
View details for DOI 10.1161/CIRCHEARTFAILURE.113.001273
View details for PubMedID 24902740
Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices.
2014; 129 (22): 2287-2296
Allogeneic mesenchymal precursor cells (MPCs) injected during left ventricular assist device (LVAD) implantation may contribute to myocardial recovery. This trial explores the safety and efficacy of this strategy.In this multicenter, double-blind, sham-procedure controlled trial, 30 patients were randomized (2:1) to intramyocardial injection of 25 million MPCs or medium during LVAD implantation. The primary safety end point was incidence of infectious myocarditis, myocardial rupture, neoplasm, hypersensitivity reaction, and immune sensitization (90 days after randomization). Key efficacy end points were functional status and ventricular function while temporarily weaned from LVAD support (90 days after randomization). Patients were followed up until transplant or 12 months after randomization, whichever came first. Mean age was 57.4 (±13.6) years, mean left ventricular ejection fraction was 18.1%, and 66.7% were destination therapy LVADs. No safety events were observed. Successful temporary LVAD weaning was achieved in 50% of MPC and 20% of control patients at 90 days (P=0.24); the posterior probability that MPCs increased the likelihood of successful weaning was 93%. At 90 days, 3 deaths (30%) occurred in control patients, and none occurred in MPC patients. Mean left ventricular ejection fraction after successful wean was 24.0% (MPC=10) and 22.5% (control=2; P=0.56). At 12 months, 30% of MPC patients and 40% of control patients were successfully temporarily weaned from LVAD support (P=0.69), and 6 deaths (30%) occurred in MPC patients. Donor-specific HLA sensitization developed in 2 MPC and 3 control patients and resolved by 12 months.In this preliminary trial, administration of MPCs appeared to be safe, and there was a potential signal of efficacy. Future studies will evaluate the potential for higher or additional doses to enhance the ability to wean LVAD recipients off support.http://www.clinicaltrials.gov. Unique identifier: NCT01442129.
View details for DOI 10.1161/CIRCULATIONAHA.113.007412
View details for PubMedID 24682346
- Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices. Circulation 2014; 129 (22): 2287-2296
Ex Vivo Allograft Mitral Valve Leaflet Repair Prior to Orthotopic Heart Transplantation
JOURNAL OF CARDIAC SURGERY
2014; 29 (3): 424-426
The shortage of donors has limited the number of heart transplantations. We report a successful ex vivo mitral valve repair of the allograft prior to heart transplantation.
View details for DOI 10.1111/jocs.12297
View details for Web of Science ID 000335168900031
View details for PubMedID 24460568
Preclinical evaluation of the engineered stem cell chemokine stromal cell-derived factor 1a analog in a translational ovine myocardial infarction model.
2014; 114 (4): 650-659
After myocardial infarction, there is an inadequate blood supply to the myocardium, and the surrounding borderzone becomes hypocontractile.To develop a clinically translatable therapy, we hypothesized that in a preclinical ovine model of myocardial infarction, the modified endothelial progenitor stem cell chemokine, engineered stromal cell-derived factor 1α analog (ESA), would induce endothelial progenitor stem cell chemotaxis, limit adverse ventricular remodeling, and preserve borderzone contractility.Thirty-six adult male Dorset sheep underwent permanent ligation of the left anterior descending coronary artery, inducing an anteroapical infarction, and were randomized to borderzone injection of saline (n=18) or ESA (n=18). Ventricular function, geometry, and regional strain were assessed using cardiac MRI and pressure-volume catheter transduction. Bone marrow was harvested for in vitro analysis, and myocardial biopsies were taken for mRNA, protein, and immunohistochemical analysis. ESA induced greater chemotaxis of endothelial progenitor stem cells compared with saline (P<0.01) and was equivalent to recombinant stromal cell-derived factor 1α (P=0.27). Analysis of mRNA expression and protein levels in ESA-treated animals revealed reduced matrix metalloproteinase 2 in the borderzone (P<0.05), with elevated levels of tissue inhibitor of matrix metalloproteinase 1 and elastin in the infarct (P<0.05), whereas immunohistochemical analysis of borderzone myocardium showed increased capillary and arteriolar density in the ESA group (P<0.01). Animals in the ESA treatment group also had significant reductions in infarct size (P<0.01), increased maximal principle strain in the borderzone (P<0.01), and a steeper slope of the end-systolic pressure-volume relationship (P=0.01).The novel, biomolecularly designed peptide ESA induces chemotaxis of endothelial progenitor stem cells, stimulates neovasculogenesis, limits infarct expansion, and preserves contractility in an ovine model of myocardial infarction.
View details for DOI 10.1161/CIRCRESAHA.114.302884
View details for PubMedID 24366171
View details for PubMedCentralID PMC4137973
Mitral-Valve Repair versus Replacement for Severe Ischemic Mitral Regurgitation
NEW ENGLAND JOURNAL OF MEDICINE
2014; 370 (1): 23-32
Ischemic mitral regurgitation is associated with a substantial risk of death. Practice guidelines recommend surgery for patients with a severe form of this condition but acknowledge that the supporting evidence for repair or replacement is limited.We randomly assigned 251 patients with severe ischemic mitral regurgitation to undergo either mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety. The primary end point was the left ventricular end-systolic volume index (LVESVI) at 12 months, as assessed with the use of a Wilcoxon rank-sum test in which deaths were categorized below the lowest LVESVI rank.At 12 months, the mean LVESVI among surviving patients was 54.6±25.0 ml per square meter of body-surface area in the repair group and 60.7±31.5 ml per square meter in the replacement group (mean change from baseline, -6.6 and -6.8 ml per square meter, respectively). The rate of death was 14.3% in the repair group and 17.6% in the replacement group (hazard ratio with repair, 0.79; 95% confidence interval, 0.42 to 1.47; P=0.45 by the log-rank test). There was no significant between-group difference in LVESVI after adjustment for death (z score, 1.33; P=0.18). The rate of moderate or severe recurrence of mitral regurgitation at 12 months was higher in the repair group than in the replacement group (32.6% vs. 2.3%, P<0.001). There were no significant between-group differences in the rate of a composite of major adverse cardiac or cerebrovascular events, in functional status, or in quality of life at 12 months.We observed no significant difference in left ventricular reverse remodeling or survival at 12 months between patients who underwent mitral-valve repair and those who underwent mitral-valve replacement. Replacement provided a more durable correction of mitral regurgitation, but there was no significant between-group difference in clinical outcomes. (Funded by the National Institutes of Health and the Canadian Institutes of Health; ClinicalTrials.gov number, NCT00807040.).
View details for DOI 10.1056/NEJMoa1312808
View details for Web of Science ID 000329354100007
View details for PubMedID 24245543
Regional Annular Geometry in Patients With Mitral Regurgitation: Implications for Annuloplasty Ring Selection
ANNALS OF THORACIC SURGERY
2014; 97 (1): 64-70
The saddle shape of the normal mitral annulus has been quantitatively described by several groups. There is strong evidence that this shape is important to valve function. A more complete understanding of regional annular geometry in diseased valves may provide a more educated approach to annuloplasty ring selection and design. We hypothesized that mitral annular shape is markedly distorted in patients with diseased valves.Real-time 3-dimensional echocardiography was performed in 20 patients with normal mitral valves, 10 with ischemic mitral regurgitation, and 20 with myxomatous mitral regurgitation (MMR). Thirty-six annular points were defined to generate a 3-dimensional model of the annulus. Regional annular parameters were measured from these renderings. Left ventricular inner diameter was obtained from 2-dimensional echocardiographic images.Annular geometry was significantly different among the three groups. The annuli were larger in the MMR and in the ischemic mitral regurgitation groups. The annular enlargement was greater and more pervasive in the MMR group. Both diseases were associated with annular flattening, although though the regional distribution of that flattening was different between groups. Left ventricular inner diameter was increased in both groups. However, relative to the Left ventricular inner diameter, the annulus was disproportionately dilated in the MMR group.Patients with MMR and ischemic mitral regurgitation have enlarged and flattened annuli. In the case of MMR, annular distortions may be the driving factor leading to valve incompetence. These data suggest that the goal of annuloplasty should be the restoration of normal annular saddle shape and that the use of flexible, partial, and flat rings may be ill advised.
View details for DOI 10.1016/j.athoracsur.2013.07.048
View details for Web of Science ID 000329155900020
View details for PubMedID 24070698
- Mesenchymal Precursor Cells as Adjunctive Therapy in Recipients of Contemporary LVADs: A Multi-Center Prospective Randomized Placebo-Controlled Double-Blinded Clinical Trial. Circulation 2014; (in press)
Nonresectional Single-Suture Leaflet Remodeling for Degenerative Mitral Regurgitation Facilitates Minimally Invasive Mitral Valve Repair
ANNALS OF THORACIC SURGERY
2013; 96 (5): 1603-1606
Both leaflet resection and neochordal construction are effective mitral repair techniques, but they may become incrementally time-consuming when using minimally invasive approaches. We have used a single-suture leaflet-remodeling technique of inverting the prolapsed or flail segment tissue into the left ventricle. This repair is straightforward, expeditious, and facilitates a minimally invasive approach.Ninety-nine patients with degenerative mitral regurgitation (MR) underwent a minimally invasive single-suture repair of the mitral valve from May 2007 through December 2012. Preoperative and perioperative echocardiograms as well as patient outcomes were analyzed and compared with those obtained from patients undergoing minimally invasive mitral valve repair using quadrangular resection at the same institution during the same period.All 99 patients had a successful mitral repair through a sternal-sparing minimally invasive approach. Ninety-one of the 99 patients had zero MR on postoperative echocardiogram, and 8 of 99 had trace to mild MR. Patients in the nonresectional group had significantly shorter cardiopulmonary bypass and cross-clamp times compared with the quadrangular resection group (115.8 ± 41.7 minutes versus 144.9 ± 38.2 minutes; p < 0.001; 76.2 ± 28.1 minutes versus 112.6 ± 33.5 minutes; p < 0.001, respectively). The mean length of stay was 7.5 ± 3 days. All patients were discharged alive and free from clinical symptoms of MR. There have been no reoperations for recurrent MR on subsequent average follow-up of 1 year.An effective, highly efficient, and thus far durable single-suture mitral leaflet-remodeling technique facilitates minimally invasive repair of degenerative MR.
View details for DOI 10.1016/j.athoracsur.2013.05.053
View details for Web of Science ID 000326375700020
View details for PubMedID 23932318
Continuous Flow Left Ventricular Assist Device Implant Significantly Improves Pulmonary Hypertension, Right Ventricular Contractility, and Tricuspid Valve Competence
JOURNAL OF CARDIAC SURGERY
2013; 28 (6): 770-775
Continuous flow left ventricular assist devices (CF LVAD) are being implanted with increasing frequency for end-stage heart failure. At the time of LVAD implant, a large proportion of patients have pulmonary hypertension, right ventricular (RV) dysfunction, and tricuspid regurgitation (TR). RV dysfunction and TR can exacerbate renal dysfunction, hepatic dysfunction, coagulopathy, edema, and even prohibit isolated LVAD implant. Repairing TR mandates increased cardiopulmonary bypass time and bicaval cannulation, which should be reserved for the time of orthotopic heart transplantation. We hypothesized that CF LVAD implant would improve pulmonary artery pressures, enhance RV function, and minimize TR, obviating need for surgical tricuspid repair.One hundred fourteen continuous flow LVADs implanted from 2005 through 2011 at a single center, with medical management of functional TR, were retrospectively analyzed. Pulmonary artery pressures were measured immediately prior to and following LVAD implant. RV function and TR were graded according to standard echocardiographic criteria, prior to, immediately following, and long-term following LVAD.There was a significant improvement in post-VAD mean pulmonary arterial pressures (26.6 ± 4.9 vs. 30.2 ± 7.4 mmHg, p = 0.008) with equivalent loading pressures (CVP = 12.0 ± 4.0 vs. 12.1 ± 5.1 p = NS). RV function significantly improved, as noted by right ventricular stroke work index (7.04 ± 2.60 vs. 6.05 ± 2.54, p = 0.02). There was an immediate improvement in TR grade and RV function following LVAD implant, which was sustained long term.Continuous flow LVAD implant improves pulmonary hypertension, RV function, and tricuspid regurgitation. TR may be managed nonoperatively during CF LVAD implant.
View details for DOI 10.1111/jocs.12214
View details for Web of Science ID 000326894300051
View details for PubMedID 24118109
Minimally Invasive Mitral Valve Surgery Can Be Performed With Optimal Outcomes in the Presence of Left Ventricular Dysfunction
49th Annual Meeting of the Society-of-Thoracic-Surgeons
ELSEVIER SCIENCE INC. 2013: 1596–1602
Minimally invasive approaches to mitral valve repair have demonstrated equivalent technical outcomes and more rapid recovery when compared with traditional sternotomy. These techniques have been widely accepted for mitral insufficiency and stenosis. The utilization of minimally invasive techniques in the presence of left ventricular (LV) dysfunction has been controversial. We hypothesized that minimally invasive mitral valve surgery could be safely performed in the presence of compromised myocardial function, thereby minimizing recovery time.All patients undergoing minimally invasive mitral valve surgery at our center from November 1998 through June 2012 were analyzed. During this time 1,103 patients underwent minimally invasive, port access, mitral valve surgery utilizing a video-assisted limited right thoracotomy approach. Patients with LV dysfunction (ejection fraction ≤ 0.40, n = 140) were compared with patients with normal ventricular function (n = 963). Preoperative, intraoperative, and postoperative variables were compared between cohorts.Patients with LV dysfunction were able to undergo mitral valve surgery with minimal mortality (2.1% vs 1.7%, p = 0.7) and morbidity, that was comparable with patients with normal ventricular function. Postoperative recovery was only slightly longer compared with patients with normal LV function as noted by time to extubation (6.0 vs 7.0 hours, p = 0.005) and hospital length of stay (7.0 vs 6.0 days, p < 0.001). A significant percentage of patients with LV dysfunction underwent redo cardiac surgery (40.0%) through minimally invasive approaches.Minimally invasive, port-access, mitral valve surgery can be safely performed with minimal morbidity and mortality in the presence of cardiomyopathy. This approach may be considered in patients with isolated mitral valve pathology and LV dysfunction in an experienced center.
View details for DOI 10.1016/j.athoracsur.2013.05.098
View details for Web of Science ID 000326375700019
View details for PubMedID 23987894
Valve-sparing aortic root replacement and neochordal repair of complex aortic leaflet pathology for ruptured sinus of valsalva aneurysm fistulizing to the right ventricle.
Annals of thoracic surgery
2013; 96 (5): 1891-1893
Sinus of Valsalva aneurysms (SVAs) are rare congenital entities arising from eccentric aortic root dilatation that can protrude and rupture into adjacent cardiac chambers. Treatment entails aneurysmal sac excision and aortic defect closure. We present a young patient with a ruptured SVA fistulizing into the right ventricle and acute decompensated heart failure. He also had moderate aortic root enlargement and a dysmorphic aortic valve with 3 highly asymmetrical leaflets. This pathologic condition was successfully repaired with a novel combination of valve-sparing root replacement, aortic valve leaflet neochordal repair, right ventricular reconstruction, and tricuspid valve annuloplasty.
View details for DOI 10.1016/j.athoracsur.2013.05.008
View details for PubMedID 24182491
- Continuous-flow left ventricular assist device implantation in the presence of a hostile ventricular apex. journal of thoracic and cardiovascular surgery 2013; 146 (4): 981-982
Valve-sparing aortic root replacement with translocation of anomalous left coronary artery.
Annals of thoracic surgery
2013; 96 (4): 1466-1469
An anomalous left main coronary artery arising from the right coronary with a single coronary ostium is an exceptionally rare anatomic variant. Here, we report a patient with a left main coronary artery arising from the right coronary and also an aortic root aneurysm associated with mild aortic insufficiency. Valve-sparing aortic root replacement and coronary translocation were performed with an excellent outcome in this case.
View details for DOI 10.1016/j.athoracsur.2013.01.090
View details for PubMedID 24088463
Sustained release of engineered stromal cell-derived factor 1-a from injectable hydrogels effectively recruits endothelial progenitor cells and preserves ventricular function after myocardial infarction.
2013; 128 (11): S79-86
Exogenously delivered chemokines have enabled neovasculogenic myocardial repair in models of ischemic cardiomyopathy; however, these molecules have short half-lives in vivo. In this study, we hypothesized that the sustained delivery of a synthetic analog of stromal cell-derived factor 1-α (engineered stromal cell-derived factor analog [ESA]) induces continuous homing of endothelial progenitor cells and improves left ventricular function in a rat model of myocardial infarction.Our previously designed ESA peptide was synthesized by the addition of a fluorophore tag for tracking. Hyaluronic acid was chemically modified with hydroxyethyl methacrylate to form hydrolytically degradable hydrogels through free-radical-initiated crosslinking. ESA was encapsulated in hyaluronic acid hydrogels during gel formation, and then ESA release, along with gel degradation, was monitored for more than 4 weeks in vitro. Chemotactic properties of the eluted ESA were assessed at multiple time points using rat endothelial progenitor cells in a transwell migration assay. Finally, adult male Wistar rats (n=33) underwent permanent ligation of the left anterior descending (LAD) coronary artery, and 100 µL of saline, hydrogel alone, or hydrogel+25 µg ESA was injected into the borderzone. ESA fluorescence was monitored in animals for more than 4 weeks, after which vasculogenic, geometric, and functional parameters were assessed to determine the therapeutic benefit of each treatment group. ESA release was sustained for 4 weeks in vitro, remained active, and enhanced endothelial progenitor cell chemotaxis. In addition, ESA was detected in the rat heart >3 weeks when delivered within the hydrogels and significantly improved vascularity, ventricular geometry, ejection fraction, cardiac output, and contractility compared with controls.We have developed a hydrogel delivery system that sustains the release of a bioactive endothelial progenitor cell chemokine during a 4-week period that preserves ventricular function in a rat model of myocardial infarction.
View details for DOI 10.1161/CIRCULATIONAHA.112.000343
View details for PubMedID 24030424
Spatially oriented, temporally sequential smooth muscle cell-endothelial progenitor cell bi-level cell sheet neovascularizes ischemic myocardium.
2013; 128 (11): S59-68
Endothelial progenitor cells (EPCs) possess robust therapeutic angiogenic potential, yet may be limited in the capacity to develop into fully mature vasculature. This problem might be exacerbated by the absence of a neovascular foundation, namely pericytes, with simple EPC injection. We hypothesized that coculturing EPCs with smooth muscle cells (SMCs), components of the surrounding vascular wall, in a cell sheet will mimic the native spatial orientation and interaction between EPCs and SMCs to create a supratherapeutic angiogenic construct in a model of ischemic cardiomyopathy.Primary EPCs and SMCs were isolated from Wistar rats. Confluent SMCs topped with confluent EPCs were spontaneously detached from the Upcell dish to create an SMC-EPC bi-level cell sheet. A rodent ischemic cardiomyopathy model was created by ligating the left anterior descending coronary artery. Rats were then immediately divided into 3 groups: cell-sheet transplantation (n=14), cell injection (n=12), and no treatment (n=13). Cocultured EPCs and SMCs stimulated an abundant release of multiple cytokines in vitro. Increased capillary density and improved blood perfusion in the borderzone elucidated the significant in vivo angiogenic potential of this technology. Most interestingly, however, cell fate-tracking experiments demonstrated that the cell-sheet EPCs and SMCs directly migrated into the myocardium and differentiated into elements of newly formed functional vasculature. The robust angiogenic effect of this cell sheet translated to enhanced ventricular function as demonstrated by echocardiography.Spatially arranged EPC-SMC bi-level cell-sheet technology facilitated the natural interaction between EPCs and SMCs, thereby creating structurally mature, functional microvasculature in a rodent ischemic cardiomyopathy model, leading to improved myocardial function.
View details for DOI 10.1161/CIRCULATIONAHA.112.000293
View details for PubMedID 24030422
Normalization of postinfarct biomechanics using a novel tissue-engineered angiogenic construct.
2013; 128 (11): S95-104
Cell-mediated angiogenic therapy for ischemic heart disease has had disappointing results. The lack of clinical translatability may be secondary to cell death and systemic dispersion with cell injection. We propose a novel tissue-engineered therapy, whereby extracellular matrix scaffold seeded with endothelial progenitor cells (EPCs) can overcome these limitations using an environment in which the cells can thrive, enabling an insult-free myocardial cell delivery to normalize myocardial biomechanics.EPCs were isolated from the long bones of Wistar rat bone marrow. The cells were cultured for 7 days in media or seeded at a density of 5 × 10(6) cells/cm(2) on a collagen/vitronectin matrix. Seeded EPCs underwent ex vivo modification with stromal cell-derived factor-1α (100 ng/mL) to potentiate angiogenic properties and enhance paracrine qualities before construct formation. Scanning electron microscopy and confocal imaging confirmed EPC-matrix adhesion. In vitro vasculogenic potential was assessed by quantifying EPC cell migration and vascular differentiation. There was a marked increase in vasculogenesis in vitro as measured by angiogenesis assay (8 versus 0 vessels/hpf; P=0.004). The construct was then implanted onto ischemic myocardium in a rat model of acute myocardial infarction. Confocal microscopy demonstrated a significant migration of EPCs from the construct to the myocardium, suggesting a direct angiogenic effect. Myocardial biomechanical properties were uniaxially quantified by elastic modulus at 5% to 20% strain. Myocardial elasticity normalized after implant of our tissue-engineered construct (239 kPa versus normal=193, P=0.1; versus infarct=304 kPa, P=0.01).We demonstrate restoration and normalization of post-myocardial infarction ventricular biomechanics after therapy with an angiogenic tissue-engineered EPC construct.
View details for DOI 10.1161/CIRCULATIONAHA.112.000368
View details for PubMedID 24030426
Pulmonary Autograft Leaflet Repair and Valve Sparing Root Replacement to Correct Late Failure of the Ross Procedure
JOURNAL OF CARDIAC SURGERY
2013; 28 (5): 496-499
Delayed pulmonary autograft failure is the principal limitation of the Ross procedure. Although reoperation typically includes replacement of the neoaortic valve, strategies for autograft valve preservation are becoming increasingly employed. However, leaflet prolapse and asymmetry are deterrents to valve preservation in this technically complex surgical population. The present report illustrates the technical considerations in performing an autograft valve preserving aortic root replacement with direct leaflet repair for the surgical correction of aortic insufficiency and root aneurysm late after a successful Ross procedure.
View details for DOI 10.1111/jocs.12150
View details for Web of Science ID 000324070400005
View details for PubMedID 23782261
Predicting Right Ventricular Failure in the Modern, Continuous Flow Left Ventricular Assist Device Era
59th Annual Meeting of the Southern-Thoracic-Surgical-Association (STSA)
ELSEVIER SCIENCE INC. 2013: 857–64
In the era of destination continuous flow left ventricular assist devices (LVAD), the decision of whether a patient will tolerate isolated LVAD support or will need biventricular support (BIVAD) can be challenging. Incorrect decision making with delayed right ventricular (RV) assist device implantation results in increased morbidity and mortality. Continuous flow LVADs have been shown to decrease pulmonary hypertension and improve RV function. We undertook this study to determine predictors in the continuous flow LVAD era that identify patients who are candidates for isolated LVAD therapy as opposed to biventricular support.We reviewed demographic, hemodynamic, laboratory, and echocardiographic variables for 218 patients who underwent VAD implant from 2003 through 2011 (LVAD=167, BIVAD=51), during the era of continuous flow LVADs.Fifty preoperative risk factors were compared between patients who were successfully managed with an LVAD and those who required a BIVAD. Seventeen variables demonstrated statistical significance by univariate analysis. Multivariable logistic regression analysis identified central venous pressure>15 mmHg (OR 2.0, "C"), severe RV dysfunction (OR 3.7, "R"), preoperative intubation (OR 4.3, "I"), severe tricuspid regurgitation (OR 4.1, "T"), heart rate>100 (OR 2.0, Tachycardia-"T")-CRITT as the major criteria predictive of the need for biventricular support. Utilizing these data, a highly sensitive and easy to use risk score for determining RV failure was generated that outperformed other established risk stratification tools.We present a preoperative risk calculator to determine suitability of a patient for isolated LVAD support in the current continuous flow ventricular assist device era.
View details for DOI 10.1016/j.athoracsur.2013.03.099
View details for Web of Science ID 000323940200026
View details for PubMedID 23791165
Posterior ventricular anchoring neochordal repair of degenerative mitral regurgitation efficiently remodels and repositions posterior leaflet prolapse(dagger)
26th Annual Meeting of the European-Association-for-Cardio-Thoracic-Surgery (EACTS)
OXFORD UNIV PRESS INC. 2013: 485–89
Mitral valve repair techniques for degenerative disease typically entail leaflet resection or neochordal construction, which may require extensive resection, leaflet detachment/reattachment, reliance on diseased native chords or precise neochordal measuring. Occasionally, impaired leaflet mobility, reduced coaptation surface and systolic anterior motion (SAM) may result. We describe a novel technique for addressing posterior leaflet prolapse/flail, which both simplifies repair and addresses these issues.Fifty-four patients (age 62 ± 11 years) with degenerative MR underwent this new repair, 36 of whom minimally-invasively. A CV5 Gore-Tex suture was placed into the posterior left ventricular myocardium underneath the prolapsing segment as an anchor. This suture was then used to imbricate a portion of the prolapsed segment into the ventricle, creating a smooth, broad, non-prolapsed coapting surface on a leaflet with preserved mobility, additional neochordal support and posteriorly positioned enough to preclude SAM.Repair was successful in all patients. The mean MR grade was reduced from +3.8 to +0.1 with 50 of 54 patients having zero MR and 4 of the 54 having trace or mild MR. All patients had proper antero-posterior location of the coaptation line of a mean length of 10.2 mm, and preserved posterior leaflet mobility. No patients had SAM or mitral stenosis. All patients were discharged and are currently doing well.This new technique facilitated efficient single-suture repair of the prolapsed posterior leaflet mitral regurgitation without the need for resection or sliding annuloplasty. It precluded the need for precise neochordal measurement and preserved the leaflet coaptation surface.
View details for DOI 10.1093/ejcts/ezt092
View details for Web of Science ID 000323350400043
View details for PubMedID 23449863
Ventricular Assist Device Implant in the Elderly Is Associated With Increased, but Respectable Risk: A Multi-Institutional Study
49th Annual Meeting of the Society-of-Thoracic-Surgeons
ELSEVIER SCIENCE INC. 2013: 141–47
There are an increasing number of elderly patients with end-stage heart failure. Destination mechanical circulatory support is often the only therapy available for these patients who are not transplant candidates. The outcomes after continuous flow left ventricular assist device (CF LVAD) implant in older patients remains unclear. We undertook this multi-institutional study to quantify short-term and midterm outcomes after CF LVAD implant in the elderly.We retrospectively analyzed all patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) national registry that underwent implant of a CF LVAD (June 2006 to April 2012). Patients were divided into 2 cohorts based upon age (<70 years [n = 4,439] and ≥ 70 years (n = 590]). Preoperative, intraoperative, and postoperative variables were analyzed. The primary endpoint, survival, was compared between cohorts.Patients age 70 and older were more hemodynamically stable pre-VAD implant as evidenced by INTERMACS profile and inotrope dependence. Perioperative outcomes, including median bypass time (89 vs 89 minutes) and length of stay (0.657 vs 0.657 months) were similar between cohorts (p = not significant). Kaplan-Meier analysis revealed a significant difference in 2-year survival between patients aged 70 years or greater (63%) and less than 70 (71%, p < 0.001). Multivariable Cox proportional hazard analysis revealed age as an independent predictor of mortality during follow-up (p < 0.001). Nonetheless, midterm cumulative survival in the older cohort was still reasonable (63% at 2 years).Multi-institutional analysis revealed advanced age as a predictor of increased mortality after CF LVAD implantation. Careful patient selection is critical in the elderly to optimize long-term outcomes after CF LVAD implantation.
View details for DOI 10.1016/j.athoracsur.2013.04.010
View details for Web of Science ID 000321741300032
View details for PubMedID 23731606
- Dissected axillary artery cannulation in redo-total arch replacement surgery JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 2013; 145 (6): E57-E59
Ascending Aortic Cannulation in Acute Type A Dissection Repair
ANNALS OF THORACIC SURGERY
2013; 95 (5): 1808-1811
Femoral and axillary cannulation for arterial inflow in acute type A aortic dissection are the most commonly used cannulation strategies in current practice. More recently, our group and others have successfully used a central cannulation technique with excellent results. Although this approach has been described, specific technical details have not been clearly defined. In addition, the ideal anatomic characteristics of different types of aortic dissections amenable to central cannulation have not been delineated. The purpose of this brief communication is to describe the technical and procedural details specific to cannulation of the dissected ascending aorta and to propose a classification scheme of ascending aortic dissection anatomy based on difficulty of central cannulation.
View details for DOI 10.1016/j.athoracsur.2012.10.086
View details for Web of Science ID 000318969500081
View details for PubMedID 23608274
Profound hyperacute cardiac allograft rejection rescue with biventricular mechanical circulatory support and plasmapheresis, intravenous immunoglobulin, and rituximab therapy
JOURNAL OF CARDIOTHORACIC SURGERY
Hyperacute rejection is a rare but potentially catastrophic complication after cardiac transplantation. We describe an unusual case of hyperacute rejection due to preformed anti-donor antibodies despite a negative preoperative panel-reactive antibody (PRA) screen. An excellent outcome was achieved in this case and our strategy involving the use of CentriMag ventricular assist devices (VADs) for biventricular support during treatment with rituximab, intravenous immunoglobulin (IVIG), and plasmapheresis is illustrated.
View details for DOI 10.1186/1749-8090-8-48
View details for Web of Science ID 000317741900001
View details for PubMedID 23497431
Minimally invasive approach provides at least equivalent results for surgical correction of mitral regurgitation: A propensity-matched comparison
38th Annual Meeting of the Western-Thoracic-Surgical-Association
MOSBY-ELSEVIER. 2013: 748–56
Minimally invasive approaches to mitral valve surgery are increasingly used, but the surgical approach must not compromise the clinical outcome for improved cosmesis. We examined the outcomes of mitral repair performed through right minithoracotomy or median sternotomy.Between January 2002 and October 2011, 1011 isolated mitral valve repairs were performed in the University of Pennsylvania health system (455 sternotomies, 556 right minithoracotomies). To account for key differences in preoperative risk profiles, propensity scores identified 201 well-matched patient pairs with mitral regurgitation of any cause and 153 pairs with myxomatous disease.In-hospital mortality was similar between propensity-matched groups (0% vs 0% for the degenerative cohort; 0% vs 0.5%, P = .5 for the overall cohort; in minimally invasive and sternotomy groups, respectively). Incidence of stroke, infection, myocardial infarction, exploration for postoperative hemorrhage, renal failure, and atrial fibrillation also were comparable. Transfusion was less frequent in the minimally invasive groups (11.8% vs 20.3%, P = .04 for the degenerative cohort; 14.0% vs 22.9%, P = .03 for the overall cohort), but time to extubation and discharge was similar. A 99% repair rate was achieved in patients with myxomatous disease, and a minimally invasive approach did not significantly increase the likelihood of a failed repair resulting in mitral valve replacement. Patients undergoing minimally invasive mitral repair were more likely to have no residual post-repair mitral regurgitation (97.4% vs 92.1%, P = .04 for the degenerative cohort; 95.5% vs 89.6%, P = .02 for the overall cohort). In the overall matched cohort, early readmission rates were higher in patients undergoing sternotomies (12.6% vs 4.4%, P = .01). Over 9 years of follow-up, there was no significant difference in long-term survival between groups (P = .8).In appropriate patients with isolated mitral valve disease of any cause, a right minithoracotomy approach may be used without compromising clinical outcome.
View details for DOI 10.1016/j.jtcvs.2012.09.093
View details for Web of Science ID 000314882500024
View details for PubMedID 23414991
Quantitative evaluation of change in coexistent mitral regurgitation after aortic valve replacement
38th Annual Meeting of the Western-Thoracic-Surgical-Association
MOSBY-ELSEVIER. 2013: 341–48
Management of intermediate degrees of mitral regurgitation during aortic valve replacement for aortic stenosis remains controversial. We sought to evaluate the degree of reduction of mitral regurgitation in patients undergoing aortic valve replacement, as well as a mathematical relationship between aortic valve gradient reduction and the degree of mitral regurgitation decrement.We retrospectively analyzed demographic, intraoperative, and echocardiographic data on 802 patients who underwent aortic valve replacement or aortic root replacement between January 2010 and March 2011. A total of 578 patients underwent aortic valve replacement or aortic root replacement without intervention on the mitral valve. We excluded 88 patients with severe aortic insufficiency, 3 patients who underwent ventricular assist device placement, 4 patients who underwent prior mitral valve replacement, and 21 patients with incomplete data, yielding 462 patients for analysis. For each patient, the degree of pre- and postoperative mitral regurgitation was graded on a standard 0 to 4+ scale.Of the 462 patients, 289 patients had at least mild mitral regurgitation. On average, mitral regurgitation decreased 0.24 degrees per patient for this cohort of 289 patients. Of the 56 patients with at least moderate mitral regurgitation, mitral regurgitation decreased 0.54 degrees per patient. Of 62 patients who underwent isolated aortic valve replacements, who had at least mild mitral regurgitation, and who had no evidence of structural mitral valve disease, mitral regurgitation decreased 0.24 degrees per patient. Linear regression analysis revealed no relationship between reduction in mitral regurgitation and gradient reduction across the aortic valve.Reduction in mitral regurgitation after relief of aortic outflow tract obstruction is modest at best. Further, the magnitude of gradient change across the aortic valve has little influence on the degree of reduction in mitral regurgitation. These observations argue at minimum for performing a prospective evaluation of the clinical benefits of addressing moderate mitral regurgitation at the time of aortic valve intervention and may support a more aggressive approach to concomitant mitral surgery.
View details for DOI 10.1016/j.jtcvs.2012.10.043
View details for Web of Science ID 000313634700010
View details for PubMedID 23245347
Rapid onset of fulminant myocarditis portends a favourable prognosis and the ability to bridge mechanical circulatory support to recovery
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
2013; 43 (2): 379-382
Fulminant myocarditis with cardiogenic shock is fatal without mechanical circulatory support. Once haemodynamic stability has been established with a ventricular assist device (VAD), the decision to wait for myocardial recovery as opposed to listing for an orthotopic heart transplant (OHT) can be difficult. We have undertaken this study to establish the criteria for determining the need for heart transplantation following VAD implant for fulminant myocarditis.A total of 442 VADs were implanted between 1993 and 2011. Twenty-four VADs were implanted for fulminant myocarditis with refractory cardiogenic shock. We retrospectively analysed the variables and the pathology for this cohort. Patients who had a full recovery of myocardial function and subsequent VAD explant (Explant) were compared with those bridged to OHT. There was one acute death.There was no difference in the past medical history between the groups. Explant patients had a more acute onset of heart failure with a median of 7 days between the onset of symptoms and VAD implant, when compared with 22 days for OHT (P = 0.01). A rapid recovery in myocardial function was seen in the Explant group, with recovery of myocardial function (ejection fraction = 53 ± 24%) in 14 ± 7 days. Myocardial function was sustained for 5 years following the VAD explant. The female gender favoured myocardial recovery and VAD explantability. Two patients had giant cell myocarditis, neither of whom had a recovery of function, and they were bridged to heart transplant with a VAD.Fulminant myocarditis is a fatal condition without mechanical support. The rapid onset of symptoms is associated with a complete recovery of myocardial function and VAD explant. The absence of rapid recovery of myocardial function should prompt listing for a heart transplant.
View details for DOI 10.1093/ejcts/ezs242
View details for Web of Science ID 000313829300031
View details for PubMedID 22564805
- 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: Executive Summary A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2013; 61 (4): 485-510
- 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction: Executive Summary A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines CIRCULATION 2013; 127 (4): 529-?
Postoperative Right Ventricular Failure After Left Ventricular Assist Device Placement is Predicted by Preoperative Echocardiographic Structural, Hemodynamic, and Functional Parameters
JOURNAL OF CARDIAC FAILURE
2013; 19 (1): 16-24
Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation results in significant morbidity and mortality. Preoperative parameters from transthoracic echocardiography (TTE) that predict RVF after LVAD implantation might identify patients in need of temporary or permanent right ventricular (RV) mechanical or inotropic support.Records of all patients who had preoperative TTE before implantation of a permanent LVAD at our institution from 2008 to 2011 were screened, and 55 patients (age 54 ± 16 years, 71% male) were included: 26 had LVAD implantation alone with no postoperative RVF, 16 had LVAD implantation alone but experienced postoperative RVF, and 13 had initial biventricular assist devices (BIVADs). The LVAD with RVF and BIVAD groups (RVF group) were pooled for comparison with the LVAD patients without RVF (No RVF group). RV fractional area change (RV FAC) was significantly lower in the RVF group versus the No RVF group (24% vs 30%; P = .04). Tricuspid annular plane systolic excursion was not different among the groups (1.6 cm vs 1.5 cm; P = .53). Estimated right atrial pressure (RAP) was significantly higher in the RVF group versus the No RVF group (11 mm Hg vs 8 mm Hg; P = .04). Left atrial volume (LAV) index was lower in patients with RVF versus No RVF (27 mL/m(2) vs 40 mL/m(2); P = .008). Combining RV FAC, estimated RAP, and LAV index into an echocardiographic scoring system revealed that the TTE score was highly predictive of RVF (5.0 vs 2.8; P = .0001). In multivariate models combining the TTE score with clinical variables, the score was the most predictive of RVF (odds ratio 1.66, 95% confidence interval 1.06-2.62).Preoperative RV FAC, estimated RAP, and LAV index predict postoperative RVF in patients undergoing LVAD implantation. These parameters may be combined into a simple echocardiographic scoring system to provide an additional tool to risk-stratify patients being evaluated for LVAD implantation.
View details for DOI 10.1016/j.cardfail.2012.11.001
View details for Web of Science ID 000313858100003
View details for PubMedID 23273590
Mathematically engineered stromal cell-derived factor-1 alpha stem cell cytokine analog enhances mechanical properties of infarcted myocardium
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2013; 145 (1): 278-284
The biomechanical response to a myocardial infarction consists of ventricular remodeling that leads to dilatation, loss of contractile function, abnormal stress patterns, and ultimately heart failure. We hypothesized that intramyocardial injection of our previously designed pro-angiogenic chemokine, an engineered stromal cell-derived factor-1α analog (ESA), improves mechanical properties of the heart after infarction.Male rats (n = 54) underwent either sham surgery (n = 17) with no coronary artery ligation or ligation of the left anterior descending artery (n = 37). The rats in the myocardial infarction group were then randomized to receive either saline (0.1 mL, n = 18) or ESA (6 μg/kg, n = 19) injected into the myocardium at 4 predetermined spots around the border zone. Echocardiograms were performed preoperatively and before the terminal surgery. After 4 weeks, the hearts were explanted and longitudinally sectioned. Uniaxial tensile testing was completed using an Instron 5543 Microtester. Optical strain was evaluated using custom image acquisition software, Digi-Velpo, and analyzed in MATLAB.Compared with the saline control group at 4 weeks, the ESA-injected hearts had a greater ejection fraction (71.8% ± 9.0% vs 55.3% ± 12.6%, P = .0004), smaller end-diastolic left ventricular internal dimension (0.686 ± 0.110 cm vs 0.763 ± 0.160 cm, P = .04), greater cardiac output (36 ± 11.6 mL/min vs 26.9 ± 7.3 mL/min, P = .05), and a lower tensile modulus (251 ± 56 kPa vs 301 ± 81 kPa, P = .04). The tensile modulus for the sham group was 195 ± 56 kPa, indicating ESA injection results in a less stiff ventricle.Direct injection of ESA alters the biomechanical response to myocardial infarction, improving the mechanical properties in the postinfarct heart.
View details for DOI 10.1016/j.jtcvs.2012.09.080
View details for Web of Science ID 000312386300047
View details for PubMedID 23244259
- Intracardiac exposure for transventricular mitral valve ring annuloplasty repair during Dor ventriculoplasty JOURNAL OF HEART AND LUNG TRANSPLANTATION 2012; 31 (11): 1236-1238
Three-Dimensional Echocardiographic Analysis of Mitral Annular Dynamics Implication for Annuloplasty Selection
Meeting of the American-Heart-Association
LIPPINCOTT WILLIAMS & WILKINS. 2012: S183–S188
Proponents of flexible annuloplasty rings have hypothesized that such devices maintain annular dynamics. This hypothesis is based on the supposition that annular motion is relatively normal in patients undergoing mitral valve repair. We hypothesized that mitral annular dynamics are impaired in ischemic mitral regurgitation and myxomatous mitral regurgitation.A Philips iE33 echocardiographic module and X7-2t probe were used to acquire full-volume real-time 3-dimensional transesophageal echocardiography loops in 11 normal subjects, 11 patients with ischemic mitral regurgitation and 11 patients with myxomatous mitral regurgitation. Image analysis was performed using Tomtec Image Arena, 4D-MV Assessment, 2.1 (Munich, Germany). A midsystolic frame was selected for the initiation of annular tracking using the semiautomated program. Continuous parameters were normalized in time to provide for uniform systolic and diastolic periods. Both ischemic mitral regurgitation (9.98 ± 155 cm(2)) and myxomatous mitral regurgitation annuli (13.29 ± 3.05 cm(2)) were larger in area than normal annuli (7.95 ± 1.40 cm(2)) at midsystole. In general, ischemic mitral regurgitation annuli were less dynamic than controls. In myxomatous mitral regurgitation, annular dynamics were also markedly abnormal with the mitral annulus dilating rapidly in early systole in response to rising ventricular pressure.In both ischemic mitral regurgitation and myxomatous mitral regurgitation, annular dynamics and anatomy are abnormal. Flexible annuloplasty devices used in mitral valve repair are, therefore, unlikely to result in either normal annular dynamics or normal anatomy.
View details for DOI 10.1161/CIRCULATIONAHA.111.084483
View details for Web of Science ID 000314150200026
View details for PubMedID 22965981
The influence of saddle-shaped annuloplasty on leaflet curvature in patients with ischaemic mitral regurgitation
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY
2012; 42 (3): 493-499
Reports indicate that repair procedures for ischaemic mitral regurgitation (IMR) are less durable than previously thought. Repair failure has been shown to be stress related. Leaflet curvature is the major determinant of valve stress. Theoretical and animal experiments have shown that saddle-shaped annuloplasty optimizes leaflet curvature when compared with standard flat ring annuloplasty. Despite this, the influence of the ring shape on leaflet curvature has not been described in patients with IMR. This study uses real-time three-dimensional echocardiography (rt-3DE) to assess the influence of the ring shape on leaflet curvature.Rt-3DE was performed in 21 patients with IMR after placement of either a flat (n = 10, CE-Physio, Edwards) or saddle-shaped (n = 11, Profile 3D, Medtronic) annuloplasty ring. A combination of commercially available and customized software was used to measure multiple leaflet curvature parameters across all regions of the mitral valve.Independently of the shape of the annuloplasty ring, all patients were subject to the same degree of annular undersizing. Patients who received saddle-shaped annuloplasty rings had greater leaflet curvature in all six mitral valve leaflet regions (A1 = 0.36 ± 0.10, A2 = 0.53 ± 0.13, A3 = 0.47 ± 0.13, P1 = 0.35 ± 0.23, P2 = 0.53 ± 0.34, P3 = 0.42 ± 0.20 cm(-2)) compared with patients who received flat annuloplasty rings (A1 = 0.16 ± 0.11, A2 = 0.18 ± 0.09, A3 = 0.16 ± 0.11, P1 = 0.20 ± 0.17, P2 = 0.21 ± 0.11, P3 = 0.18 ± 0.13 cm(-2)). These differences were statistically significant in all regions except the P1 region.Saddle-shaped annuloplasty rings increase leaflet curvature compared with flat rings in patients with IMR. As a result, saddle-shaped annuloplasty may decrease leaflet stress and potentially increases the durability of the repair in patients with IMR.
View details for DOI 10.1093/ejcts/ezs040
View details for Web of Science ID 000307784500018
View details for PubMedID 22351705
- Aortic valve repair by sinotubular junctional remodeling to eliminate aortic regurgitation in donor cardiac allograft JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 2012; 144 (3): 722-724
- Thoracoabdominal aortic aneurysm. Annals of cardiothoracic surgery 2012; 1 (3): 277-285
Re-Engineered Stromal Cell-Derived Factor-1 alpha and the Future of Translatable Angiogenic Polypeptide Design
TRENDS IN CARDIOVASCULAR MEDICINE
2012; 22 (6): 139-144
Smaller engineered analogs of angiogenic cytokines may provide translational advantages, including enhanced stability and function, ease of synthesis, lower cost, and, most important, the potential for modulated delivery via engineered biomaterials. In order to create such a peptide, computational molecular modeling and design was employed to engineer a minimized, highly efficient polypeptide analog of the stromal cell-derived factor-1α (SDF) molecule. After removal of the large, central β-sheet region, a designed diproline linker connected the native N-terminus (responsible for receptor activation and binding) and C-terminus (responsible for extracellular stabilization). This yielded energetic and conformational advantages resulting in a small, low-molecular-weight engineered SDF polypeptide analog (ESA) that was shown to have angiogenic activity comparable to or better than that of recombinant human SDF both in vitro and in a murine model of ischemic heart failure.
View details for Web of Science ID 000311065900001
View details for PubMedID 22902182
Transaortic Mitral Valve Replacement
ANNALS OF THORACIC SURGERY
2012; 94 (1): 302-304
Transaortic replacement of the mitral valve at the time of aortic valve or root replacement is a rarely used technique that offers many possible advantages in the setting of multivalve replacement. Reports in the literature are few and dated. The purpose of this brief communication is to describe technical and procedural details specific to mitral procedures done through the aortic annulus.
View details for DOI 10.1016/j.athoracsur.2012.01.081
View details for Web of Science ID 000305801600068
View details for PubMedID 22735004
Effects of Atrial Fibrillation on Treatment of Mitral Regurgitation in the EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) Randomized Trial
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
2012; 59 (14): 1312-1319
The purpose of this study was to characterize patients with mitral regurgitation (MR) and atrial fibrillation (AF) treated percutaneously using the MitraClip device (Abbott Vascular, Abbott Park, Illinois) and compare the results with surgery in this population.The EVEREST II (Endovascular Valve Edge-to-Edge Repair Study) randomized controlled trial compared a less invasive catheter-based treatment for MR with surgery, providing an opportunity to assess the impact of AF on the outcomes of both the MitraClip procedure and surgical repair.The study population included 264 patients with moderately severe or severe MR assessed by an independent echocardiographic core laboratory. Comparison of safety and effectiveness study endpoints at 30 days and 1 year were made using both intention-to-treat and per-protocol (cohort of patients with MR ≤2+ at discharge) analyses.Pre-existing AF was present in 27% of patients. These patients were older, had more advanced disease, and were more likely to have a functional etiology. Similar reduction of MR to ≤2+ before discharge was achieved in patients with AF (83%) and in patients without AF (75%, p = 0.3). Freedom from death, mitral valve surgery for valve dysfunction, and MR >2+ was similar at 12 months for AF patients (64%) and for no-AF patients (61%, p = 0.3). At 12 months, MR reduction to <2+ was greater with surgery than with MitraClip, but there was no interaction between rhythm and MR reduction, and no difference in all-cause mortality between patients with and patients without AF.Atrial fibrillation is associated with more advanced valvular disease and noncardiac comorbidities. However, acute procedural success, safety, and 1-year efficacy with MitraClip therapy is similar for patients with AF and without AF.
View details for DOI 10.1016/j.jacc.2011.12.023
View details for Web of Science ID 000302140800009
View details for PubMedID 22464260
Myocardial tissue elastic properties determined by atomic force microscopy after stromal cell-derived factor 1 alpha angiogenic therapy for acute myocardial infarction in a murine model
37th Annual Meeting of the Western-Thoracic-Surgical-Association
MOSBY-ELSEVIER. 2012: 962–66
Ventricular remodeling after myocardial infarction begins with massive extracellular matrix deposition and resultant fibrosis. This loss of functional tissue and stiffening of myocardial elastic and contractile elements starts the vicious cycle of mechanical inefficiency, adverse remodeling, and eventual heart failure. We hypothesized that stromal cell-derived factor 1α (SDF-1α) therapy to microrevascularize ischemic myocardium would rescue salvageable peri-infarct tissue and subsequently improve myocardial elasticity.Immediately after left anterior descending coronary artery ligation, mice were randomly assigned to receive peri-infarct injection of either saline solution or SDF-1α. After 6 weeks, animals were killed and samples were taken from the peri-infarct border zone and the infarct scar, as well as from the left ventricle of noninfarcted control mice. Determination of tissues' elastic moduli was carried out by mechanical testing in an atomic force microscope.SDF-1α-treated peri-infarct tissue most closely approximated the elasticity of normal ventricle and was significantly more elastic than saline-treated peri-infarct myocardium (109 ± 22.9 kPa vs 295 ± 42.3 kPa; P < .0001). Myocardial scar, the strength of which depends on matrix deposition from vasculature at the peri-infarct edge, was stiffer in SDF-1α-treated animals than in controls (804 ± 102.2 kPa vs 144 ± 27.5 kPa; P < .0001).Direct quantification of myocardial elastic properties demonstrates the ability of SDF-1α to re-engineer evolving myocardial infarct and peri-infarct tissues. By increasing elasticity of the ischemic and dysfunctional peri-infarct border zone and bolstering the weak, aneurysm-prone scar, SDF-1α therapy may confer a mechanical advantage to resist adverse remodeling after infarction.
View details for DOI 10.1016/j.jtcvs.2011.12.028
View details for Web of Science ID 000301609200036
View details for PubMedID 22264415
- Simplified nonresectional leaflet remodeling mitral valve repair for degenerative mitral regurgitation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 2012; 143 (3): 749-753
Design, rationale, and initiation of the Surgical Interventions for Moderate Ischemic Mitral Regurgitation Trial: A report from the Cardiothoracic Surgical Trials Network
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2012; 143 (1): 111-U175
Patients with coronary artery disease complicated by moderate ischemic mitral regurgitation have demonstrably poorer outcome than do patients with coronary artery disease but without mitral regurgitation. The optimal treatment of this condition has become increasingly controversial, and a randomized trial evaluating current practices is warranted.We describe the design and initial execution of the Cardiothoracic Surgical Trials Network Surgical Interventions for Moderate Ischemic Mitral Regurgitation Trial.This is an ongoing prospective, multicenter, randomized, controlled clinical trial designed to test the safety and efficacy of mitral repair in addition to coronary artery bypass grafting in the treatment of moderate ischemic mitral regurgitation.The results of the Cardiothoracic Surgical Trials Network Surgical Interventions for Moderate Ischemic Mitral Regurgitation Trial will provide long-awaited information on controversial therapies for this morbid disease process.
View details for DOI 10.1016/j.jtcvs.2011.05.006
View details for Web of Science ID 000298151800018
View details for PubMedID 21788032
Durability of Porcine Bioroots in Younger Patients With Aortic Root Pathology: A Propensity-Matched Comparison With Composite Mechanical Roots
Surgical Motion Picture Session of the 46th Annual Meeting of the Society-of-Thoracic-Surgeons
ELSEVIER SCIENCE INC. 2011: 2054–61
We present a comparison of porcine bioroot and composite mechanical root replacement in a large series of patients younger than 60 years who required full root replacement for true root pathology.Between 1997 and 2007, we performed 986 aortic root replacement procedures, including 391 porcine bioroots and 515 composite mechanical roots for true root indications. Of these, 504 patients were younger than 60 years old at time of the operation. Porcine bioroots were placed in 138 patients, including 38 St. Jude Toronto Root (St. Jude Inc, St. Paul, MN), 98 Medtronic Freestyle (Medtronic Inc, Minneapolis, MN), and 2 Edwards Prima (Edwards Lifesciences Inc, Irvine, CA). Standard univariate, logistic regression, Cox regression, and propensity matching techniques were used.To adjust for baseline differences in risk factor profiles, propensity matching yielded a final matched data set of 128 matched pairs, with no differences in preoperative risk factor profile or indication for operation. Overall 30-day operative mortality was 2.3% for porcine bioroot patients vs 1.6% for mechanical root patients (p = 0.6). Root type did not influence early (odds ratio, 0.8; 96% confidence interval, 0.2 to 3.2) or late mortality (hazard risk, 1.4; 95% confidence interval, 0 0.5 to 3.8). Multivariate predictors of late mortality included (hazard ratio, 95% confidence interval) age in years (1.01; 1.01 to 1.03), chronic renal failure (3.6; 1.1 to 12.6), and preoperative bacterial endocarditis (3.6; 1.1 to 11.8). Freedom from reoperation was similar between groups; however, bleeding events were more common among mechanical root patients.Porcine bioroots provide durable midterm to late-term outcomes after aortic root replacement for true root indications and are an appealing alternative in younger patients because they limit morbidity associated with anticoagulant-related bleeding.
View details for DOI 10.1016/j.athoracsur.2011.02.020
View details for Web of Science ID 000297333300026
View details for PubMedID 21839980
Who Needs an RVAD in Addition to an LVAD?
2011; 29 (4): 599-?
Mechanical circulatory support using left ventricular assist devices (LVAD) has become an accepted mode of therapy for both bridging patients with end-stage heart failure to transplant and as a destination therapy. Right ventricular (RV) dysfunction is common after LVAD insertion and is a significant source of morbidity and mortality in patients undergoing LVAD placement. Several studies have identified clinical, laboratory, hemodynamic, and echocardiographic parameters that may serve as risk factors for RV dysfunction after LVAD placement. Furthermore, scoring systems have been established to help quantitatively predict the potential need for RV support after LVAD placement.
View details for DOI 10.1016/j.ccl.2011.08.011
View details for Web of Science ID 000297822800018
View details for PubMedID 22062210
Transventricular mitral valve operations.
Annals of thoracic surgery
2011; 92 (4): 1501-1503
We report transventricular mitral valve operations in 2 patients with severe mitral regurgitation and postinfarction left ventricular rupture and pseudoaneurysm. The first patient had direct papillary muscle involvement necessitating replacement of the mitral valve. The second patient had indirect mitral involvement allowing for placement of an atrial mitral annuloplasty ring via the left ventricle. Both patients showed no mitral valve regurgitation after replacement or repair and had uneventful postoperative recoveries. These cases demonstrate a feasible, alternative, transventricular approach to mitral valve replacement and repair.
View details for DOI 10.1016/j.athoracsur.2010.10.065
View details for PubMedID 21958802
Computational Protein Design to Reengineer Stromal Cell-Derived Factor-1 alpha Generates an Effective and Translatable Angiogenic Polypeptide Analog
Annual Meeting of the American-Heart-Association
LIPPINCOTT WILLIAMS & WILKINS. 2011: S18–S26
Experimentally, exogenous administration of recombinant stromal cell-derived factor-1α (SDF) enhances neovasculogenesis and cardiac function after myocardial infarction. Smaller analogs of SDF may provide translational advantages including enhanced stability and function, ease of synthesis, lower cost, and potential modulated delivery via engineered biomaterials. In this study, computational protein design was used to create a more efficient evolution of the native SDF protein.Protein structure modeling was used to engineer an SDF polypeptide analog (engineered SDF analog [ESA]) that splices the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a diproline segment designed to limit the conformational flexibility of the peptide backbone and retain the relative orientation of these segments observed in the native structure of SDF. Endothelial progenitor cells (EPCs) in ESA gradient, assayed by Boyden chamber, showed significantly increased migration compared with both SDF and control gradients. EPC receptor activation was evaluated by quantification of phosphorylated AKT, and cells treated with ESA yielded significantly greater phosphorylated AKT levels than SDF and control cells. Angiogenic growth factor assays revealed a distinct increase in angiopoietin-1 expression in the ESA- and SDF-treated hearts. In addition, CD-1 mice (n=30) underwent ligation of the left anterior descending coronary artery and peri-infarct intramyocardial injection of ESA, SDF-1α, or saline. At 2 weeks, echocardiography demonstrated a significant gain in ejection fraction, cardiac output, stroke volume, and fractional area change in mice treated with ESA compared with controls.Compared with native SDF, a novel engineered SDF polypeptide analog (ESA) more efficiently induces EPC migration and improves post-myocardial infarction cardiac function and thus offers a more clinically translatable neovasculogenic therapy.
View details for DOI 10.1161/CIRCULATIONAHA.110.009431
View details for Web of Science ID 000294782800003
View details for PubMedID 21911811
Saddle-shape annuloplasty increases mitral leaflet coaptation after repair for flail posterior leaflet.
Annals of thoracic surgery
2011; 92 (3): 797-803
The primary goal of surgical mitral repair is the reestablishment of normal leaflet coaptation. Surgical techniques that maintain or restore leaflet geometry promote leaflet coaptation. Recent 3-dimensional (3D) echocardiographic studies have shown that saddle-shaped annuloplasty has a salutary influence on leaflet geometry. Therefore we hypothesized that saddle-shaped annuloplasty would improve leaflet coaptation in cases of repair for flail posterior leaflet segments.Sixteen patients with flail posterior segment and severe mitral regurgitation had valve repair using standard techniques. Eight patients received saddle-shaped annuloplasty and 8 patients received flat annuloplasty. Real-time 3D transesophageal echocardiography was performed before and after repair. Images were analyzed using custom software to calculate mitral annular area (MAA), septolateral dimension (SLD), intercommissural width (CW), total leaflet area (TLA), and leaflet coaptation area (LCA).Postrepair MAA (flat, 588.6±26.5 mm2; saddle, 628.0±35.3 mm2; p=0.12) and TLA (flat, 2198.5±151.6 mm2; saddle, 2303.9±183.8 mm2; p=0.67) were similar in both groups. Postrepair LCA was significantly greater in the saddle group than in the flat group (226.8±24.0 mm2 and 154.0±13.0 mm2, respectively; p=0.02).Real-time 3D echocardiography and novel imaging software provide a powerful tool for analyzing mitral leaflet coaptation. When compared with flat annuloplasty, saddle-shaped annuloplasty improves LCA after mitral valve repair for severe mitral regurgitation secondary to flail posterior leaflet segment. Use of saddle-shaped annuloplasty devices may increase repair durability.
View details for DOI 10.1016/j.athoracsur.2011.04.047
View details for PubMedID 21803330
Oxygen-dependent quenching of phosphorescence used to characterize improved myocardial oxygenation resulting from vasculogenic cytokine therapy
JOURNAL OF APPLIED PHYSIOLOGY
2011; 110 (5): 1460-1465
This study evaluates a therapy for infarct modulation and acute myocardial rescue and utilizes a novel technique to measure local myocardial oxygenation in vivo. Bone marrow-derived endothelial progenitor cells (EPCs) were targeted to the heart with peri-infarct intramyocardial injection of the potent EPC chemokine stromal cell-derived factor 1α (SDF). Myocardial oxygen pressure was assessed using a noninvasive, real-time optical technique for measuring oxygen pressures within microvasculature based on the oxygen-dependent quenching of the phosphorescence of Oxyphor G3. Myocardial infarction was induced in male Wistar rats (n = 15) through left anterior descending coronary artery ligation. At the time of infarction, animals were randomized into two groups: saline control (n = 8) and treatment with SDF (n = 7). After 48 h, the animals underwent repeat thoracotomy and 20 μl of the phosphor Oxyphor G3 was injected into three areas (peri-infarct myocardium, myocardial scar, and remote left hindlimb muscle). Measurements of the oxygen distribution within the tissue were then made in vivo by applying the end of a light guide to the beating heart. Compared with controls, animals in the SDF group exhibited a significantly decreased percentage of hypoxic (defined as oxygen pressure ≤ 15.0 Torr) peri-infarct myocardium (9.7 ± 6.7% vs. 21.8 ± 11.9%, P = 0.017). The peak oxygen pressures in the peri-infarct region of the animals in the SDF group were significantly higher than the saline controls (39.5 ± 36.7 vs. 9.2 ± 8.6 Torr, P = 0.02). This strategy for targeting EPCs to vulnerable peri-infarct myocardium via the potent chemokine SDF-1α significantly decreased the degree of hypoxia in peri-infarct myocardium as measured in vivo by phosphorescence quenching. This effect could potentially mitigate the vicious cycle of myocyte death, myocardial fibrosis, progressive ventricular dilatation, and eventual heart failure seen after acute myocardial infarction.
View details for DOI 10.1152/japplphysiol.01138.2010
View details for Web of Science ID 000290472400043
View details for PubMedID 21292844
Tissue-Specific Variability in Human Epicardial Impedance
JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY
2011; 22 (4): 436-439
Epicardial ablation can be employed to treat ventricular tachycardia. Voltage attenuation in regions of fat can mimic epicardial scar, limiting its specificity. Ablation over fat may not be as effective. Prior animal data have shown that infarcted myocardium has lower impedance than normal, and human bioimpedance studies suggest peripheral fat displays higher impedance. Therefore, we tested the hypothesis that human epicardial fat has higher impedance than myocardium when measured with standard ablation tools.Patients undergoing elective surgery for coronary artery or valve disease were enrolled. A reference patch was placed on the patients' back between the scapulae and connected to a standard RF generator (Stockert, GmBH, Germany). Impedance was measured by passing a 1 μA, 50 kHz current from the catheter tip to the patch. After sternotomy but before initiation of cardiopulmonary bypass, an ablation catheter (Celsius, Biosense Webster, Diamond Bar, CA, USA) was placed onto the epicardial surface in ventricular regions visually identified as fat or myocardium. At each site, impedance was recorded from the generator.A total of 37 (7 patients) points were sampled. Impedance was significantly higher in regions of fat versus normal muscle (697 Ω vs. 301 Ω; P = 0.01). Moreover, normal sites from the LV had higher impedance than from the RV (381 Ω vs. 271 Ω; P = 0.01).Human epicardial fat has higher tissue impedance than normal muscle. Using epicardial impedance and voltage mapping in conjunction may improve differentiation of arrhythmia substrate from epicardial fat and improve the efficacy of epicardial ablation.
View details for DOI 10.1111/j.1540-8167.2010.01929.x
View details for Web of Science ID 000289470700013
View details for PubMedID 20946231
Forecasting the Future of Cardiovascular Disease in the United States A Policy Statement From the American Heart Association
2011; 123 (8): 933-944
Cardiovascular disease (CVD) is the leading cause of death in the United States and is responsible for 17% of national health expenditures. As the population ages, these costs are expected to increase substantially.To prepare for future cardiovascular care needs, the American Heart Association developed methodology to project future costs of care for hypertension, coronary heart disease, heart failure, stroke, and all other CVD from 2010 to 2030. This methodology avoided double counting of costs for patients with multiple cardiovascular conditions. By 2030, 40.5% of the US population is projected to have some form of CVD. Between 2010 and 2030, real (2008$) total direct medical costs of CVD are projected to triple, from $273 billion to $818 billion. Real indirect costs (due to lost productivity) for all CVD are estimated to increase from $172 billion in 2010 to $276 billion in 2030, an increase of 61%.These findings indicate CVD prevalence and costs are projected to increase substantially. Effective prevention strategies are needed if we are to limit the growing burden of CVD.
View details for DOI 10.1161/CIR.0b013e31820a55f5
View details for Web of Science ID 000287801300021
View details for PubMedID 21262990
Outcomes of coronary artery bypass grafting and reduction annuloplasty for functional ischemic mitral regurgitation: A prospective multicenter study (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve)
36th Annual Meeting of the Western-Thoracic-Surgical-Association
MOSBY-ELSEVIER. 2011: 91–97
Functional ischemic mitral regurgitation is a complication of ventricular remodeling; standard therapy is reduction annuloplasty and coronary artery bypass grafting. Unfortunately, outcomes are retrospective and contradictory. We report a multicenter study that documents the outcomes of reduction annuloplasty for functional ischemic mitral regurgitation.Twenty-one centers randomized 75 patients to the coronary artery bypass grafting + reduction annuloplasty subgroup that was the control arm of the Randomized Evaluation of a Surgical Treatment for Off-pump Repair of the Mitral Valve trial. Entry criteria included patients requiring revascularization, patients with severe or symptomatic moderate functional ischemic mitral regurgitation, an ejection fraction 25% or greater, a left ventricular end-diastolic dimension 7.0 cm or less, and more than 30 days since acute myocardial infarction. All echocardiograms were independently scored by a core laboratory. Reduction annuloplasty was achieved by device annuloplasty. Two patients underwent immediate intraoperative conversion to a valve replacement because reduction annuloplasty was unable to correct mitral regurgitation; as-treated results are presented.Thirty-day mortality was 4.1% (3/73). Patients received an average of 2.8 bypass grafts. Mean follow-up was 24.6 months. Mitral regurgitation was reduced from 2.6 ± 0.8 preoperatively to 0.3 ± 0.6 at 2 years. Freedom from death or valve reoperation was 78% ± 5% at 2 years. There was significant improvement in ejection fraction and New York Heart Association class with reduction of left ventricular end-diastolic dimension. Cox regression analyses suggested that increasing age (P = .001; hazard ratio, 1.16 per year; 95% confidence interval, 1.06-1.26) and renal disease (P = .018; hazard ratio, 3.48; 95% confidence interval, 1.25-9.72) were associated with decreased survival.Coronary artery bypass grafting + reduction annuloplasty for functional ischemic mitral regurgitation predictably reduces mitral regurgitation and relieves symptoms. This treatment of moderate to severe mitral regurgitation is associated with improved indices of ventricular function, improved New York Heart Association class, and excellent freedom from recurrent mitral insufficiency. Although long-term prognosis remains guarded, this multicenter study delineates the intermediate-term benefits of such an approach.
View details for DOI 10.1016/j.jtcvs.2010.08.057
View details for Web of Science ID 000285407500019
View details for PubMedID 21168015
Mechanical Circulatory Assistance - An Evolving Therapy
2011; 75 (1): 38-46
Although heart transplantation is the gold standard for the treatment of advanced stage heart failure, the implantation of mechanical circulatory support devices (MCSDs) has become a well-established therapy for this disease. As the population of patients with severe heart failure has grown, the utilization of MCSDs has increased considerably. That trend is expected to continue, especially in light of dramatic advances in MCSD technology. This review outlines the current status and future directions of mechanical circulatory support therapy in the setting of a constantly evolving field of supportive devices and adjuvant therapies.
View details for DOI 10.1253/circj.CJ-10-1091
View details for Web of Science ID 000285814300005
Minimally invasive robotic mitral valve surgery
EXPERT REVIEW OF MEDICAL DEVICES
2011; 8 (1): 115-120
Over the past two decades, significant advances have been made in mitral valve surgery. Cardiac surgeons have successfully repaired degenerative and ischemic regurgitant mitral valves via a traditional midline sternotomy. In recent years, alternate incisions have yielded minimally invasive approaches to the mitral valve. Technological advances have made robotically assisted minimally invasive mitral valve surgery feasible. Decreased pain, more rapid return to work, diminished blood loss and reduced length of hospitalization have been witnessed following robotic mitral valve surgery when compared with a traditional sternotomy. Equivalent long-term mortality and freedom from recurrent mitral regurgitation are evident between mitral valve repair performed via a traditional sternotomy and minimally invasive and robotic techniques. As a result, an increasing number of patients and referring cardiologists are seeking minimally invasive approaches to mitral valve surgery.
View details for DOI 10.1586/ERD.10.66
View details for Web of Science ID 000289451500017
View details for PubMedID 21158546
Implantable Ventricular Assist Device Exchange With Focused Intravascular Deairing Techniques
ANNALS OF THORACIC SURGERY
2011; 91 (1): 306-307
As ventricular assist devices are increasingly adopted and widely implemented as a highly effective therapy for end-stage heart disease, extended utilization periods for destination therapy or bridge-to-transplantation have created the possibility of device failure, infection, or thrombosis, requiring challenging implant exchanges. A major problem in these operations is the risk of air embolization, particularly in a nonsternotomy approach that precludes access to the outflow aortic graft and to the ascending aorta. We report a minimally invasive, nonsternotomy HeartMate II implantable left ventricular assist device (LVAD) exchange, using peripheral cardiopulmonary support and a novel approach to continuous intravascular ascending aortic air removal.
View details for DOI 10.1016/j.athoracsur.2010.04.012
View details for Web of Science ID 000285411700063
View details for PubMedID 21172546
Outcomes of the RESTOR-MV Trial (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve)
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
2010; 56 (24): 1984-1993
we sought to determine whether patients with functional mitral regurgitation (FMR) would benefit from ventricular reshaping by the Coapsys device (Myocor, Inc., Maple Grove, Minnesota).FMR occurs when ventricular remodeling impairs valve function. Coapsys is a ventricular shape change device placed without cardiopulmonary bypass to reduce FMR. It compresses the mitral annulus and reshapes the ventricle. We hypothesized that Coapsys for FMR would improve clinical outcomes compared with standard therapies.RESTOR-MV (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve) was a randomized, prospective, multicenter study of patients with FMR and coronary disease with core laboratory analysis. After enrollment, patients were stratified to the standard indicated surgery: either coronary artery bypass graft alone or coronary artery bypass graft with mitral valve repair. In each stratum, randomization was to either control (indicated surgery) or treatment (coronary artery bypass graft with Coapsys ventricular reshaping).the study was terminated when the sponsor failed to secure ongoing funding; 165 patients were randomized. Control and Coapsys both produced decreases in left ventricular (LV) end-diastolic dimension and MR at 2 years (p < 0.001); Coapsys provided a greater decrease in LV end-diastolic dimension (p = 0.021). Control had lower MR grades during follow-up (p = 0.01). Coapsys showed a survival advantage compared with control at 2 years (87% vs. 77%) (hazard ratio: 0.421; 95% confidence interval: 0.200 to 0.886; stratified log-rank test; p = 0.038). Complication-free survival (including death, stroke, myocardial infarction, and valve reoperation) was significantly greater with Coapsys at 2 years (85% vs. 71%) (hazard ratio: 0.372; 95% confidence interval: 0.185 to 0.749; adjusted log-rank test; p = 0.019).analysis of RESTOR-MV indicates that patients with FMR requiring revascularization treated with ventricular reshaping rather than standard surgery had improved survival and a significant decrease in major adverse outcomes. This trial validates the concept of the ventricular reshaping strategy in this subset of patients with heart failure. (Randomized Evaluation of a Surgical Treatment for Off-Pump Repair of the Mitral Valve [RESTOR-MV]; NCT00120276).
View details for DOI 10.1016/j.jacc.2010.06.051
View details for Web of Science ID 000284822500003
View details for PubMedID 21126639
Acute Myocardial Rescue with Endogenous Endothelial Progenitor Cell Therapy
HEART LUNG AND CIRCULATION
2010; 19 (11): 644-654
Post-myocardial infarction heart failure is a major health concern with limited therapy. Molecular revascularisation utilising granulocyte-macrophage colony stimulating factor (GMCSF) mediated endothelial progenitor cell (EPC) upregulation and stromal cell derived factor-1α (SDF) mediated myocardial EPC chemokinesis, may prevent myocardial loss and adverse remodelling. Vasculogenesis, viability, and haemodynamic improvements following therapy were investigated.Lewis rats (n=91) underwent LAD ligation and received either intramyocardial SDF and subcutaneous GMCSF or saline injections at the time of infarction. Molecular and haemodynamic assessments were performed at pre-determined time points following ligation.SDF/GMCSF therapy upregulated EPC density as shown by flow cytometry (0.12±0.02% vs. 0.06±0.01% circulating lymphocytes, p=0.005), 48hours following infarction. A marked increase in perfusion was evident eight weeks after therapy, utilising confocal angiography (5.02±1.7×10(-2)μm(3)blood/μm(3)myocardial tissue vs. 2.03±0.710(-2)μm(3)blood/μm(3)myocardial tissue, p=0.00004). Planimetric analysis demonstrated preservation of wall thickness (0.98±0.09mm vs. 0.67±0.06mm, p=0.003) and ventricular diameter (7.81±0.99mm vs. 9.41±1.1mm, p=0.03). Improved haemodynamic function was evidenced by echocardiography and PV analysis (ejection fraction: 56.4±18.1% vs. 25.3±15.6%, p=0.001; pre-load adjusted maximal power: 6.6±2.6mW/μl(2) vs. 2.7±1.4mW/μl(2), p=0.01).Neovasculogenic therapy with GMCSF-mediated EPC upregulation and SDF-mediated EPC chemokinesis maybe an effective therapy for infarct modulation and preservation of myocardial function following acute myocardial infarction.
View details for DOI 10.1016/j.hlc.2010.06.1056
View details for Web of Science ID 000283908600002
View details for PubMedID 20719564
Spliced stromal cell-derived factor-1 alpha analog stimulates endothelial progenitor cell migration and improves cardiac function in a dose-dependent manner after myocardial infarction
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2010; 140 (5): 1174-1180
Stromal cell-derived factor (SDF)-1α is a potent endogenous endothelial progenitor cell (EPC) chemokine and key angiogenic precursor. Recombinant SDF-1α has been demonstrated to improve neovasculogenesis and cardiac function after myocardial infarction (MI) but SDF-1α is a bulky protein with a short half-life. Small peptide analogs might provide translational advantages, including ease of synthesis, low manufacturing costs, and the potential to control delivery within tissues using engineered biomaterials. We hypothesized that a minimized peptide analog of SDF-1α, designed by splicing the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a truncated amino acid linker, would induce EPC migration and preserve ventricular function after MI.EPC migration was first determined in vitro using a Boyden chamber assay. For in vivo analysis, male rats (n = 48) underwent left anterior descending coronary artery ligation. At infarction, the rats were randomized into 4 groups and received peri-infarct intramyocardial injections of saline, 3 μg/kg of SDF-1α, 3 μg/kg of spliced SDF analog, or 6 μg/kg spliced SDF analog. After 4 weeks, the rats underwent closed chest pressure volume conductance catheter analysis.EPCs showed significantly increased migration when placed in both a recombinant SDF-1α and spliced SDF analog gradient. The rats treated with spliced SDF analog at MI demonstrated a significant dose-dependent improvement in end-diastolic pressure, stroke volume, ejection fraction, cardiac output, and stroke work compared with the control rats.A spliced peptide analog of SDF-1α containing both the N- and C- termini of the native protein induced EPC migration, improved ventricular function after acute MI, and provided translational advantages compared with recombinant human SDF-1α.
View details for DOI 10.1016/j.jtcvs.2010.08.012
View details for Web of Science ID 000283057600043
View details for PubMedID 20951261
Stromal Cell-Derived Factor-1 alpha Activation of Tissue-Engineered Endothelial Progenitor Cell Matrix Enhances Ventricular Function After Myocardial Infarction by Inducing Neovasculogenesis
82nd National Conference and Exhibitions and Annual Scientific Session of the American-Heart-Association
LIPPINCOTT WILLIAMS & WILKINS. 2010: S107–S117
Myocardial ischemia causes cardiomyocyte death, adverse ventricular remodeling, and ventricular dysfunction. Endothelial progenitor cells (EPCs) have been shown to ameliorate this process, particularly when activated with stromal cell-derived factor-1α (SDF), known to be the most potent EPC chemokine. We hypothesized that implantation of a tissue-engineered extracellular matrix (ECM) scaffold seeded with EPCs primed with SDF could induce borderzone neovasculogenesis, prevent adverse geometric remodeling, and preserve ventricular function after myocardial infarction.Lewis rats (n=82) underwent left anterior descending artery ligation to induce myocardial infarction. EPCs were isolated, characterized, and cultured on a vitronectin/collagen scaffold and primed with SDF to generate the activated EPC matrix (EPCM). EPCM was sutured to the anterolateral left ventricular wall, which included the region of ischemia. Control animals received sutures but no EPCM. Additional groups underwent application of the ECM alone, ECM primed with SDF (ECM+SDF), and ECM seeded with EPCs but not primed with SDF (ECM+SDF). At 4 weeks, borderzone myocardial tissue demonstrated increased levels of vascular endothelial growth factor in the EPCM group. When compared to controls, Vessel density as assessed by immunohistochemical microscopy was significantly increased in the EPCM group (4.1 versus 6.2 vessels/high-powered field; P<0.001), and microvascular perfusion measured by lectin microangiography was enhanced 4-fold (0.7% versus 2.7% vessel volume/section volume; P=0.04). Comparisons to additional groups also showed a significantly improved vasculogenic response in the EPCM group. Ventricular geometry and scar fraction assessed by digital planimetric analysis of sectioned hearts exhibited significantly preserved left ventricular internal diameter (9.7 mm versus 8.6 mm; P=0.005) and decreased infarct scar formation expressed as percent of total section area (16% versus 7%; P=0.002) when compared with all other groups. In addition, EPCM animals showed a significant preservation of function as measured by echocardiography, pressure-volume conductance, and Doppler flow.Extracellular matrix seeded with EPCs primed with SDF induces borderzone neovasculogenesis, attenuates adverse ventricular remodeling, and preserves ventricular function after myocardial infarction.
View details for DOI 10.1161/C1RCULATIONAHA.109.930404
View details for Web of Science ID 000282294800017
View details for PubMedID 20837901
Tissue-engineered pro-angiogenic fibroblast scaffold improves myocardial perfusion and function and limits ventricular remodeling after infarction
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2010; 140 (3): 667-676
Microvascular malperfusion after myocardial infarction leads to infarct expansion, adverse remodeling, and functional impairment. Native reparative mechanisms exist but are inadequate to vascularize ischemic myocardium. We hypothesized that a 3-dimensional human fibroblast culture (3DFC) functions as a sustained source of angiogenic cytokines, thereby augmenting native angiogenesis and limiting adverse effects of myocardial ischemia.Lewis rats underwent ligation of the left anterior descending coronary artery to induce heart failure; experimental animals received a 3DFC scaffold to the ischemic region. Border-zone tissue was analyzed for the presence of human fibroblast surface protein, vascular endothelial growth factor, and hepatocyte growth factor. Cardiac function was assessed with echocardiography and pressure-volume conductance. Hearts underwent immunohistochemical analysis of angiogenesis by co-localization of platelet endothelial cell adhesion molecule and alpha smooth muscle actin and by digital analysis of ventricular geometry. Microvascular angiography was performed with fluorescein-labeled lectin to assess perfusion.Immunoblotting confirmed the presence of human fibroblast surface protein in rats receiving 3DFC, indicating survival of transplanted cells. Increased expression of vascular endothelial growth factor and hepatocyte growth factor in experimental rats confirmed elution by the 3DFC. Microvasculature expressing platelet endothelial cell adhesion molecule/alpha smooth muscle actin was increased in infarct and border-zone regions of rats receiving 3DFC. Microvascular perfusion was also improved in infarct and border-zone regions in these rats. Rats receiving 3DFC had increased wall thickness, smaller infarct area, and smaller infarct fraction. Echocardiography and pressure-volume measurements showed that cardiac function was preserved in these rats.Application of a bioengineered 3DFC augments native angiogenesis through delivery of angiogenic cytokines to ischemic myocardium. This yields improved microvascular perfusion, limits infarct progression and adverse remodeling, and improves ventricular function.
View details for DOI 10.1016/j.jtcvs.2009.12.037
View details for Web of Science ID 000281116000026
View details for PubMedID 20363480
Cavopulmonary Bypass to Facilitate Infrahepatic Vena Cava Gunshot Wound Repair
ANNALS OF THORACIC SURGERY
2010; 89 (6): 2026-2028
Traumatic injuries to the inferior vena cava continue to be associated with high mortality. The management of these injuries has been technically challenging and highly variable, often depending on factors that include the anatomic complexity and the severity of the insult. We report the first case in which a patient with massive exsanguination from an infrahepatic vena cava gunshot wound underwent successful repair with the aid of a novel variant active venovenous bypass circuit between the inferior vena cava and the pulmonary artery.
View details for DOI 10.1016/j.athoracsur.2009.10.014
View details for Web of Science ID 000277934200059
View details for PubMedID 20494078
Retrograde and Antegrade Cerebral Perfusion: Results in Short Elective Arch Reconstructive Times
Surgical Motion Picture Session of the 45th Annual Meeting of the Society-of-Thoracic-Surgeons
ELSEVIER SCIENCE INC. 2010: 1448–57
Debate remains regarding optimal cerebral circulatory management during relatively noncomplex, short arch reconstructive times. Both retrograde cerebral perfusion with deep hypothermic circulatory arrest (RCP/DHCA) and antegrade cerebral perfusion with moderate hypothermic circulatory arrest (ACP/MHCA) have emerged as established techniques. The aim of the study was to evaluate perioperative outcomes between antegrade and retrograde cerebral perfusion techniques for elective arch reconstruction times less than 45 minutes.Between 1997 and September 2008, 776 cases from two institutions were reviewed to compare RCP/DHCA and ACP/MHCA perfusion techniques. At the University of Pennsylvania, 682 were treated utilizing RCP/DHCA cerebral protection. At the University of Bologna, 94 were treated with ACP/MHCA and bilateral cerebral perfusion.Mean cerebral ischemic time and visceral ischemic time differed between RCP/DHCA and ACP/MHCA (p < 0.001). Multivariate analysis showed age more than 65 years, atherosclerotic aneurysm, and cross-clamp time as predictors of the composite endpoint of mortality, neurologic event, and acute myocardial infarction. There was no significant difference in permanent neurologic deficit, temporary neurologic dysfunction, or renal failure, between RCP/DHCA and ACP/MHCA. Mortality was comparable across both techniques.Both RCP/DHCA and ACP/MHCA have emerged as effective techniques for selected aortic arch operations with low morbidity and mortality. Univariate analysis revealed no statistically significant differences in primary or secondary outcomes between techniques for aortic reconstruction times less than 45 minutes. Data from this study demonstrate that selective use of either RCP/DHCA or ACP/MHCA provides excellent cerebral and visceral outcomes for elective open aortic surgery with short arch reconstructive times.
View details for DOI 10.1016/j.athoracsur.2010.01.056
View details for Web of Science ID 000276991200016
View details for PubMedID 20417760
Repair of type A aortic dissection in nonagenarian.
Asian cardiovascular & thoracic annals
2010; 18 (2): 183-184
Without emergency surgical management, acute type A aortic dissection carries a high risk of death. Controversy exists as to whether extreme age remains a contraindication to surgery. We describe successful repair of type A aortic dissection with ascending aortic graft replacement, aortic valve repair, hemiarch reconstruction, and ablation of atrial fibrillation in a 93-year-old man.
View details for DOI 10.1177/0218492310361628
View details for PubMedID 20304857
Surgical Revision After Percutaneous Mitral Repair With the MitraClip Device
44th Annual Meeting of the Society-of-Thoracic-Surgeons
ELSEVIER SCIENCE INC. 2010: 72–80
Percutaneous mitral repair with the MitraClip device (Evalve, Menlo Park, CA) has been reported. Preserving conventional surgical options in the event of percutaneous treatment failure is important. We describe surgical treatment at varying intervals after the MitraClip procedure in 32 patients.One hundred seven patients with moderate-to-severe or severe mitral regurgitation who were either symptomatic (91%) or, if asymptomatic (9%), had evidence of left ventricular dysfunction were enrolled as part of the Endovascular Valve Edge-to-Edge REpair STudy (EVEREST) phase I registry study or as "roll-in" subjects in the EVEREST II study. Thirty-two of the 107 patients (30%) underwent surgery after an attempted MitraClip procedure.Of the 32 patients undergoing post-clip mitral valve surgery, 23 patients (72%) had one or more clips implanted and 9 patients (28%) received no clip implant. The indications for mitral valve surgery in the 23 patients with a clip included partial clip detachment (n = 10), residual or recurrent mitral regurgitation greater than 2+ (n = 9), and other (atrial septal defect [n = 2], device malfunction [n = 1], and incorrectly diagnosed mitral stenosis [n = 1]). Twenty-seven of 31 patients (87%) underwent the surgical procedure planned before surgery (planned procedure unknown in 1 patient). Four of 25 patients (16%) with planned repair underwent mitral valve replacement.Standard surgical options were preserved in patients who had surgery after percutaneous repair with the MitraClip device. Successful repair was feasible in the majority of patients after the MitraClip procedure, with repair performed as late as 18 months after clip implantation.
View details for DOI 10.1016/j.athoracsur.2009.08.063
View details for Web of Science ID 000272939700011
View details for PubMedID 20103209
Late Surgical Mitral Valve Repair after Percutaneous Repair with the MitraClip (R) System
JOURNAL OF CARDIAC SURGERY
2009; 24 (6): 677-681
Percutaneous approaches for treating mitral regurgitation are under investigation, including repair with the MitraClip percutaneous mitral repair system (Evalve, Inc., Menlo Park, CA, USA), which has undergone extensive preclinical and clinical evaluation in the EVEREST I and II trials. The procedure involves the transcatheter placement of one or two MitraClip devices under echocardiographic and fluoroscopic guidance to restore leaflet coaptation. A desirable feature of any percutaneous mitral valve (MV) repair system is that the device should not impede subsequent surgical repair if needed. To date, the majority of reported MV surgeries after MitraClip device implantation have occurred earlier, within one year of treatment. We herein describe four previously unreported cases of successful surgical MV repair up to five years after MitraClip device implantation, demonstrating that late MV repair remains possible, including after implantation of two clips.
View details for DOI 10.1111/j.1540-8191.2009.00901.x
View details for Web of Science ID 000271523400015
View details for PubMedID 19682161
Antegrade Thoracic Stent Grafting During Repair of Acute DeBakey I Dissection Prevents Development of Thoracoabdominal Aortic Aneurysms
55th Annual Meeting of the Southern-Thoracic-Surgical-Association
ELSEVIER SCIENCE INC. 2009: 482–90
Acute DeBakey I dissection repair consists of ascending aortic resection, aortic root repair or replacement, and variable aortic arch replacement. This "proximal" strategy leaves most patients with a patent residual "type B" dissection which leads to greater than 30% distal "open" reoperations for dissecting aneurysm. This report tests whether antegrade stent-grafting of the proximal descending thoracic aorta during acute DeBakey I dissection decreases future distal aortic aneurysms without an increase in surgical risk.Between June 2005 and June 2008, 150 patients were treated surgically for acute type A aortic dissection at the Hospital of the University of Pennsylvania. Of these, 78 were DeBakey I dissections: 42 patients underwent standard open repair, while 36 underwent additional thoracic stent-grafting by the open arch. Arch repairs were performed with a combination of retrograde cerebral and selective antegrade perfusion.Mean follow-up was 15.9 months. Hospital mortality was 5 of 36 (14%) for stented and 6 of 42 (14%) for nonstented repairs. Postoperative strokes were 1 of 36 (3%) in stented versus 4 of 42 (10%) in nonstented repairs (p = not significant [NS]) despite longer circulatory arrest times in the stented group; 60 +/- 13 minutes versus 41 +/- 18 minutes (p < 0.0001). Transient paraparesis was 3 of 36 (9%) in the stented versus 1 of 42 (2%) in the nonstented group (p = NS) with no permanent deficits. Stented thoracic false lumen obliteration was achieved in 24 of 30 (80%) with 5 of these (17%) achieving complete thoracoabdominal false lumen thrombosis. Eight of 31 (26%) stented patients underwent endovascular reintervention to achieve the desired false lumen obliteration. Open thoracoabdominal aortic aneurysm repairs were performed in 0 of 31 in the stented group and 4 of 36 (11%) in the standard group (p = 0.083).Antegrade stent graft deployment during acute DeBakey I dissection repair is a safe method to obliterate the thoracic false lumen. Endovascular reinterventions were well-tolerated. "Elephant trunk" thoracic stent-grafting as part of the repair for acute DeBakey I dissection gives equal short-term results compared with standard repair, and lowers morbidity and mortality during follow-up.
View details for DOI 10.1016/j.athoracsur.2009.04.046
View details for Web of Science ID 000268316400019
View details for PubMedID 19632398
Minimally Invasive Valve Surgery
SURGICAL CLINICS OF NORTH AMERICA
2009; 89 (4): 923-?
Traditional cardiac valve replacement surgery is being rapidly supplanted by innovative, minimally invasive approaches toward the repair of these valves. Patients are experiencing benefits ranging from less bleeding and pain to faster recovery and greater satisfaction. These operations are proving to be safe, highly effective, and durable, and their use will likely continue to increase and become even more widely applicable.
View details for DOI 10.1016/j.suc.2009.05.005
View details for Web of Science ID 000270918500013
View details for PubMedID 19782845
Early planned institution of biventricular mechanical circulatory support results in improved outcomes compared with delayed conversion of a left ventricular assist device to a biventricular assist device
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2009; 137 (4): 971-977
It is generally accepted that patients who require biventricular assist device support have poorer outcomes than those requiring isolated left ventricular assist device support. However, it is unknown how the timing of biventricular assist device insertion affects outcomes. We hypothesized that planned biventricular assist device insertion improves survival compared with delayed conversion of left ventricular assist device support to biventricular assist device support.We reviewed and compared outcomes of 266 patients undergoing left ventricular assist device or biventricular assist device placement at the University of Pennsylvania from April 1995 to June 2007. We subdivided patients receiving biventricular assist devices into planned biventricular assist device (P-BiVAD) and delayed biventricular assist device (D-BiVAD) groups based on the timing of right ventricular assist device insertion. We defined the D-BiVAD group as any failure of isolated left ventricular assist device support.Of 266 patients who received left ventricular assist devices, 99 (37%) required biventricular assist device support. We compared preoperative characteristics, successful bridging to transplantation, survival to hospital discharge, and Kaplan-Meier 1-year survival between the P-BiVAD (n = 71) and D-BiVAD (n = 28) groups. Preoperative comparison showed that patients who ultimately require biventricular support have similar preoperative status. Left ventricular assist device (n = 167) outcomes in all categories exceeded both P-BiVAD and D-BiVAD group outcomes. Furthermore, patients in the P-BiVAD group had superior survival to discharge than patients in the D-BiVAD group (51% vs 29%, P < .05). One-year and long-term Kaplan-Meier survival distribution confirmed this finding. There was also a trend toward improved bridging to transplantation in the P-BiVAD (n = 55) versus D-BiVAD (n = 22) groups (65% vs 45%, P = .10).When patients at high risk for failure of isolated left ventricular assist device support are identified, proceeding directly to biventricular assist device implantation is advised because early institution of biventricular support results in dramatic improvement in survival.
View details for DOI 10.1016/j.jtcvs.2008.09.021
View details for Web of Science ID 000264562000028
View details for PubMedID 19327526
Off-pump, minimally invasive and robotic coronary revascularization yield improved outcomes over traditional on-pump CABG
INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY
2009; 5 (1): 1-12
Coronary artery disease is a global health concern, with increasing morbidity and mortality. Surgical coronary artery bypass grafting has been performed on cardiopulmonary bypass for nearly four decades, with excellent long-term durability. Beating-heart coronary surgery has been increasing in frequency in an attempt to decrease cardiopulmonary bypass-related morbidity. Furthermore, with increasing expertise and technology, minimally invasive and robotic techniques have been developed to enhance post-operative recovery, patient satisfaction and cosmesis. Several clinical trials have demonstrated decreased morbidity and more rapid recovery following off-pump, minimally invasive and robotic procedures when compared to on-pump coronary artery bypass grafts (CABGs). An equivalent extent of revascularization and medium-term anastomotic patency has been demonstrated among all approaches. Furthermore, for a large number of patients who do not have anatomy amenable to traditional coronary revascularization, adjunctive molecular therapies may provide alternative myocardial micro-revascularization.
View details for DOI 10.1002/rcs.230
View details for Web of Science ID 000263998300001
View details for PubMedID 19117020
Endocarditis with massive aortic root abscess and atrioventricular septal destruction.
Interactive cardiovascular and thoracic surgery
2009; 8 (2): 280-282
Endocarditis involving the aortic root and intervalvular fibrous skeleton presents a reconstructive dilemma. We report a case of endocarditis involving the aortic root and tricuspid valve with extensive destruction of the atrioventricular septum. Debridement necessitated resection of the aortic root, aortic valve, tricuspid valve, and a large portion of atrioventricular septum, leaving the right atrium, right ventricle, left ventricle and aorta in open communication. Reconstruction was accomplished by separating the left and right hearts with a Dacron patch, tricuspid valve replacement, and aortic root replacement. Proper planar localization of the aortic root was necessary to avoid left ventricular outflow obstruction and coronary torsion.
View details for DOI 10.1510/icvts.2008.181966
View details for PubMedID 19042930
Outcomes Using Extracorporeal Life Support for Adult Respiratory Failure due to Status Asthmaticus
2009; 55 (1): 47-52
Our objective was to describe the outcomes for extracorporeal life support (ECLS) use in adult respiratory failure because of status asthmaticus and to determine whether ECLS use in status asthmaticus is associated with greater survival than other indications for ECLS. This retrospective cohort study used the multicenter, International ECLS Organization Registry. The study population included 1,257 adults with respiratory failure requiring ECLS. Status asthmaticus was the primary indication for ECLS in 24 patients. A total of 83.3% of asthmatics survived to hospital discharge compared with 50.8% of nonasthmatics (n=1,233) [odds ratio (OR) favoring survival for asthmatics=4.86, 95% confidence interval (CI) 1.65-14.31, p=0.004]. The survival advantage for asthmatics remained significant after adjustment for potential confounders. Complications were noted in 19 of 24 asthmatics (79.2%). In conclusion, we found that status asthmaticus, as an indication for ECLS in adult respiratory failure, seemed to be associated with greater survival than other indications for ECLS. However, complications are common and whether ECLS confers a survival advantage compared with other salvage treatment options remains unknown. More detailed information and complete reporting of ECLS use for status asthmaticus are needed to determine whether and when the potentially life-saving intervention of ECLS should be initiated in the asthmatic failing conventional therapy.
View details for DOI 10.1097/MAT.0b013e3181901ea5
View details for Web of Science ID 000262425400011
View details for PubMedID 19092662
Neurologic Outcomes from High Risk Descending Thoracic and Thoracoabdominal Aortic Operations in the Era of Endovascular Repair
2008; 9 (3): 344-351
Spinal cord ischemia and stroke are recognized complications of descending thoracic (DTA) and thoracoabdominal aortic (TAA) operations. However, there are limited data available on outcomes since the advent of thoracic endovascular aortic repair (TEVAR).We reviewed charts from consecutive patients who underwent open DTA and TAA operations, excluding type IV repair, from January, 2000 through April, 2005.A total of 224 open DTA and TAA operations were included in the analysis. During this period 108 additional patients received TEVAR, accounting for 66% of all DTA repairs. Among the 224 patients who underwent open surgery, 63 patients (28%) developed spinal ischemia postprocedure, 13 (6%) had a stroke, and 9 (4%) had both. The 30 day in-hospital mortality was 18%. Neurologic complications were strongly associated with mortality: 64% of patients with stroke died compared to 17% without (P < 0.001) and 39% of patients with spinal ischemia died compared to 14% without (P < 0.001). At discharge, 29% had a poor outcome from surgery, defined as death or moderate-to-severe neurologic disability. A multivariable logistic regression incorporating characteristics known prior to surgery resulted in a score to stratify risk of poor outcome by giving one point each for age > or =60, history of cerebrovascular disease, Crawford extent II or III repair, and acute rupture. Patients with score > or =3 had an estimated 60% risk for poor outcome, while those with score < or =1 had an estimated risk of 7-11%.Ischemic neurologic complications were frequent and strongly associated with poor outcomes after open DTA and TAA repair among patients not eligible for TEVAR. Risk of death or neurologic disability can be estimated based on factors known prior to surgery.
View details for DOI 10.1007/s12028-008-9104-9
View details for Web of Science ID 000260542100011
View details for PubMedID 18483880
Risk Score Derived from Pre-operative Data Analysis Predicts the Need for Biventricular Mechanical Circulatory Support
28th Annual Meeting of the International-Society-for-Heart-and-Lung-Transplantation
ELSEVIER SCIENCE INC. 2008: 1286–92
Right ventricular (RV) failure after left ventricular assist device (LVAD) placement is a serious complication and is difficult to predict. In the era of destination therapy and the total artificial heart, predicting post-LVAD RV failure requiring mechanical support is extremely important.We reviewed patient characteristics, laboratory values and hemodynamic data from 266 patients who underwent LVAD placement at the University of Pennsylvania from April 1995 to June 2007.Of 266 LVAD recipients, 99 required RV assist device (BiVAD) placement (37%). We compared 36 parameters between LVAD (n = 167) and BiVAD patients (n = 99) to determine pre-operative risk factors for RV assist device (RVAD) need. By univariate analysis, 23 variables showed statistically significant differences between the two groups (p < or = 0.05). By multivariate logistic regression, cardiac index < or =2.2 liters/min/m(2) (odds ratio [OR] 5.7), RV stroke work index < or =0.25 mm Hg . liter/m(2) (OR 5.1), severe pre-operative RV dysfunction (OR 5.0), pre-operative creatinine > or =1.9 mg/dl (OR 4.8), previous cardiac surgery (OR 4.5) and systolic blood pressure < or =96 mm Hg (OR 2.9) were the best predictors of RVAD need.The most significant predictors for RVAD need were cardiac index, RV stroke work index, severe pre-operative RV dysfunction, creatinine, previous cardiac surgery and systolic blood pressure. Using these data, we constructed an algorithm that can predict which LVAD patients will require RVAD with >80% sensitivity and specificity.
View details for DOI 10.1016/j.healun.2008.09.006
View details for Web of Science ID 000261772600004
View details for PubMedID 19059108
Acute myocardial infarction requiring mechanical bridge to transplantation in a patient with undiagnosed anti-phospholipid antibody syndrome
JOURNAL OF HEART AND LUNG TRANSPLANTATION
2008; 27 (6): 682-684
We present a young man who sustained an acute myocardial infarction with hemodynamic instability requiring placement of a left ventricular assist device and subsequent cardiac transplantation. Hematologic work-up revealed anti-phospholipid antibody syndrome. To our knowledge this is the first reported case of severe acute heart failure due to anti-phospholipid antibody syndrome in which the patient survived through assist device placement and successful transplantation.
View details for DOI 10.1016/j.healun.2008-03.002
View details for Web of Science ID 000256597500016
View details for PubMedID 18503970
Cardiac retransplantation is an efficacious therapy for primary cardiac allograft failure
JOURNAL OF CARDIOTHORACIC SURGERY
Although orthotopic heart transplantation has been an effective treatment for end-stage heart failure, the incidence of allograft failure has increased, necessitating treatment options. Cardiac retransplantation remains the only viable long-term solution for end-stage cardiac allograft failure. Given the limited number of available donor hearts, the long term results of this treatment option need to be evaluated.709 heart transplants were performed over a 20 year period at our institution. Repeat cardiac transplantation was performed in 15 patients (2.1%). A retrospective analysis was performed to determine the efficacy of cardiac retransplantation. Variables investigated included: 1 yr and 5 yr survival, length of hospitalization, post-operative complications, allograft failure, recipient and donor demographics, renal function, allograft ischemic time, UNOS listing status, blood group, allograft rejection, and hemodynamic function.Etiology of primary graft failure included transplant arteriopathy (n = 10), acute rejection (n = 3), hyperacute rejection (n = 1), and a post-transplant diagnosis of metastatic melanoma in the donor (n = 1). Mean age at retransplantation was 45.5 +/- 9.7 years. 1 and 5 year survival for retransplantation were 86.6% and 71.4% respectively, as compared to 90.9% and 79.1% for primary transplantation. Mean ejection fraction was 67.3 +/- 12.2% at a mean follow-up of 32.6 +/- 18.5 mos post-retransplant; follow-up biopsy demonstrated either ISHLT grade 1A or 0 rejection (77.5 +/- 95.7 mos post-transplant).Cardiac retransplantation is an efficacious treatment strategy for cardiac allograft failure.
View details for DOI 10.1186/1749-8090-3-26
View details for Web of Science ID 000262855000001
View details for PubMedID 18462494
Transmyocardial revascularization to enhance myocardial vasculogenesis and hemodynamic function
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2008; 135 (2): 283-U50
A significant number of patients have coronary artery disease that is not amenable to traditional revascularization. Prospective, randomized clinical trials have demonstrated therapeutic benefits with transmyocardial laser revascularization in this cohort. The molecular mechanisms underlying this therapy, however, are poorly understood. The focus of this study was evaluation of the proposed vasculogenic mechanisms involved in transmyocardial laser revascularization.Male Yorkshire pigs (30-35 kg, n = 25) underwent left thoracotomy and placement of ameroid constrictors around the proximal left circumflex coronary artery. During the next 4 weeks, a well-defined region of myocardial ischemia developed, and the animals underwent a redo left thoracotomy. The animals were randomly assigned to sham treatment (thoracotomy only, control, n = 11) or transmyocardial laser revascularization of hibernating myocardium with a holmium:yttrium-aluminum-garnet laser (n = 14). After an additional 4 weeks, the animals underwent median sternotomy, echocardiographic analysis of wall motion, and hemodynamic analysis with an ascending aortic flow probe and pulmonary artery catheter. The hearts were explanted for molecular analysis.Molecular analysis demonstrated statistically significant increases in the proangiogenic proteins nuclear factor kappaB (42 +/- 27 intensity units vs 591 +/- 383 intensity units, P = .03) and angiopoietin 1 (0 +/- 0 intensity units vs 241 +/- 87 intensity units, P = .003) relative to sham control values with transmyocardial laser revascularization within the ischemic myocardium. There were also increases in vasculogenesis (18.8 +/- 8.7 vessels/high-power field vs 31.4 +/- 10.2 vessels/high-power field, P = .02), and perfusion (0.028 +/- 0.009 microm3 blood/microm3 tissue vs 0.044 +/- 0.004 microm3 blood/microm3 tissue, P = .01). Enhanced myocardial viability was demonstrated by increased myofilament density (40.7 +/- 8.5 cardiomyocytes/high-power field vs 50.8 +/- 7.5 cardiomyocytes/high-power field, P = .03). Regional myocardial function within the treated territory demonstrated augmented contractility. Global hemodynamic function was significantly improved relative to the control group with transmyocardial laser revascularization (cardiac output 2.1 +/- 0.2 L/min vs 2.7 +/- 0.2 L/min, P = .007, mixed venous oxygen saturation 64.7% +/- 3.6% vs 76.1% +/- 3.4%, P = .008).Transmyocardial laser revascularization with the holmium-YAG laser enhances perfusion, with resultant improvement in myocardial contractility.
View details for DOI 10.1016/j.jtcvs.2007.09.043
View details for Web of Science ID 000252830400009
View details for PubMedID 18242252
Pro-angiogenic cytokines as cardiovascular therapeutics - Assessing the potential
2008; 22 (4): 209-222
Coronary artery and peripheral vascular disease are global health concerns with limited therapies. Currently available medical and surgical therapies for these disease processes are highly effective for only a fraction of patients. Extensive effort has been devoted to finding molecular therapies to enhance perfusion and function of ischemic myocardial and peripheral skeletal muscle. Angiogenic cytokines (fibroblast growth factor [FGF], vascular endothelial growth factor [VEGF], hepatocyte growth factor [HGF], placental growth factor, stromal cell-derived factor-1alpha) have shown theoretical and experimental promise in upregulating endogenous endothelial progenitor cell-mediated angiogenesis. Preliminary clinical trials have suggested improvements in myocardial and peripheral perfusion following therapy with FGF, VEGF, and HGF. Further studies on the efficacy of cytokine-mediated angiogenesis are required before widespread clinical application is possible. Investigation into adjunctive cytokine therapies for myocardial and peripheral muscle ischemia is warranted. Based on experimental evidence, appropriate angiogenic cytokine therapy should provide benefits in both perfusion and hemodynamic function.
View details for Web of Science ID 000258127300001
View details for PubMedID 18611064
Fate of the residual distal and proximal aorta after acute type a dissection repair using a contemporary surgical reconstruction algorithm
43rd Annual Meeting of the Society-of-Thoracic-Surgeons
ELSEVIER SCIENCE INC. 2007: 1955–64
In this study, we evaluated the long-term results of our contemporary, standardized surgical management algorithm for repair of acute type A aortic dissections. Prior reports have analyzed heterogeneous techniques and populations.From 1993 to 2004, 221 consecutive patients underwent repair of acute type A aortic dissection at our aortic center. Hemiarch repair was performed in 97.7% (216 of 221), and total arch in 2.3% (5 of 221). Of these, 72.9% (161 of 221) underwent aortic valve resuspension, and 27.1% (60 of 221) had aortic root replacement.In-hospital mortality for a primary operation was 12.7% (28 of 221). Actuarial survival was 79.2% at 1 year, 62.8% at 5 years, and 46.3% at 10 years. Significant risk factors for decreased survival included prior stroke, cerebral malperfusion, and length of cardiopulmonary bypass. Freedom from proximal reoperation after aortic valve resuspension was 94.6% at 5 years and 76.8% at 10 years, with cardiac malperfusion as the main risk factor. Freedom from distal reoperation was 87.6% at 5 years and 76.4% at 10 years, with Marfan syndrome, age, and extent of dissection as significant risk factors for reoperation. In-hospital mortality was 18.2% (2 of 11) after proximal reoperation and 31.2% (5 of 16) after distal reoperation.We report improved long-term durability of our proximal root repair, with cardiac malperfusion as a significant risk factor. Marfan disease, younger age, and DeBakey type I dissection are risk factors for distal reoperation. To further improve long-term outcome, means to prevent progression of distal aortic disease need to be developed.
View details for DOI 10.1016/j.athoracsur.2007.07.017
View details for Web of Science ID 000251176300022
View details for PubMedID 18036916
Emergency extracorporeal life support for asphyxic status asthmaticus
35th Critical Care Congress of the Society-of-Critical-Care-Medicine
DAEDALUS ENTERPRISES INC. 2007: 1525–29
We report a case of successful use of extracorporeal life support (ECLS) as salvage treatment in an adult with acute, severe, reversible respiratory failure due to asphyxic status asthmaticus. Conventional measures were ineffective to combat the dynamic hyperinflation; the patient had intrinsic positive end-expiratory pressure > 30 cm H(2)O. We initiated emergency ECLS at the bedside, and after 55 hours of ECLS his respiratory mechanics had markedly improved and he was subsequently weaned off of ECLS and decannulated, without vascular, pulmonary, or neurologic complications. This article reviews the history of ECLS for adult respiratory failure and its application for life-threatening status asthmaticus. This case illustrates the effective use of ECLS for acute respiratory failure due to asphyxic status asthmaticus, and to our knowledge is the first reported case in which the patient's impending cardiopulmonary arrest was due to an unsustainable level of intrinsic positive end-expiratory pressure.
View details for Web of Science ID 000250788200012
View details for PubMedID 17971256
Significance of malperfusion syndromes prior to contemporary surgical repair for acute type A dissection: outcomes and need for additional revascularizations
55th Annual Meeting of the Scandinavian-Association-for-Thoracic-Surgery/26th Annual Meeting of the Scandinavian-Society-for-Extracorporeal-Technology
OXFORD UNIV PRESS INC. 2007: 255–62
The aim of this study was to assess the significance of malperfusion syndromes in patients with acute type A aortic dissection following a contemporary surgical management algorithm and the effects on morbidity, hospital mortality, and long-term survival. We believe that obliteration of the primary tear site with restoration of flow in the true aortic lumen results in decreased need for revascularization of malperfused organ systems.Our operative approach aims at replacing the entire ascending aorta, resuspension of the aortic valve with repair or replacement of the sinus segment, and routine open replacement of the arch under hypothermic circulatory arrest with retrograde cerebral perfusion with obliteration of false lumen at the distal arch/proximal descending thoracic aorta, thus reestablishing normal flow in the descending thoracic true lumen. From January 1993 to December 2004, 221 consecutive patients underwent repair of acute type A aortic dissection at our institution. Data were collected retrospectively and prospectively. Various types of malperfusion syndromes were present in 26.7% of patients. The organ systems with malperfusion were as follows: cardiac, 7.2%; cerebral, 7.2%; ileofemoral, 12.7%; renal, 4.1%; mesenteric, 1.4%; innominate, 5.4%; and spine, 2.2%.Coronary malperfusion required coronary revascularization in 62.5% of cases. Distal revascularization was needed in 42.9% of patients with ileofemoral malperfusion. Patients with malperfusion were more likely to suffer perioperative myocardial infarction (p<0.001), postoperative coma (p=0.012), delirium (p=0.011), sepsis (p=0.006), acute renal failure (p=0.017), dialysis (p=0.018), and acute limb ischemia (p<0.001). The in-hospital mortality was 30.5% in patients presenting with any malperfusion syndrome while only 6.2% in patients without malperfusion syndrome (p<0.001). Both cardiac (p=0.020) and cerebral malperfusions (p<0.001) were risk factors for in-hospital mortality. The actuarial long-term survival in patients with malperfusion syndrome was estimated by Kaplan-Meier methods to be 67.8%+/-6.1% at 1 year, 54.0%+/-7.0% at 5 years, and 43.1%+/-8.0% at 10 years and for patient without malperfusion 82.7%+/-3.0% at 1 year, 66.3%+/-3.9% at 5 years, and 46.1%+/-6.7% at 10 years (log rank 2.55, p=0.110). Cerebral malperfusion was a significant risk factor for decreased long-term survival (p=0.0002).The occurrence of malperfusion in patients with acute type A dissection is associated with significant increased risk of in-hospital mortality and complications. Additional revascularization is generally needed in patients with coronary malperfusion and ileofemoral malperfusion. Patients presenting with cardiac and cerebral malperfusions have a high hospital mortality and preoperative cerebral malperfusion is associated with dismal long-term survival.
View details for DOI 10.1016/j.ejcts.2007.04.012
View details for Web of Science ID 000249150300012
View details for PubMedID 17500002
Association between elevated whole blood Epstein-Barr virus (EBV)-encoded RNA EBV polymerase chain reaction and reduced incidence of acute lung allograft rejection
JOURNAL OF HEART AND LUNG TRANSPLANTATION
2007; 26 (8): 839-844
Accurate functional assessment of patient immunosuppression after solid-organ transplantation remains elusive. Despite therapeutic serum immunosuppressive drug levels many lung transplant recipients still develop allograft rejection. We investigated the hypothesis that detection of latent Epstein-Barr virus (EBV) in peripheral blood may be a functional marker for the net effects of administered immunosuppression.A retrospective analysis was performed on data obtained from a prospective trial investigating the ability of a novel EBV polymerase chain reaction (PCR) panel for LMP (latent membrane protein 1), EBNA (EBV nuclear antigen) and EBER (EBV-encoded RNA) to predict future development of post-transplant lymphoproliferative disorder (PTLD). Thirty-one lung transplant patients were followed for up to 2 years after transplantation with EBV PCR panels performed on plasma and whole blood. Patients were assessed for occurrences of Grade 2 or higher acute rejection and episodes of infection.Patients with whole blood EBER-positive PCR had a statistically significant lower incidence (45% vs 83%) of Grade 2 or higher acute allograft rejection than patients with no positive assays (odds ratio [OR] = 0.17, 95% confidence interval [CI] 0.021 to 1.2, p = 0.048). Positive whole blood EBER PCR did not correlate with increased risk for infectious complications (OR = 1.6, 95% CI 0.22 to 11, p = 0.69).These results suggest that whole blood EBER EBV PCR load may represent an important functional measure of immunosuppression in solid-organ transplant patients.
View details for DOI 10.1016/j.healun.2007.05.009
View details for Web of Science ID 000248992200010
View details for PubMedID 17692789
Minimally invasive resection of papillary fibroelastoma in a high-risk patient
JOURNAL OF CARDIOVASCULAR MEDICINE
2007; 8 (8): 639-641
Papillary fibroelastomas are rare, benign cardiac tumors that typically mandate surgical resection. These are usually approached through a median sternotomy with cardioplegic arrest and aortic cross-clamping. We describe the minimally invasive resection of a right atrial fibroelastoma performed on a beating heart via right mini-thoracotomy in a patient complicated by a previous laryngectomy, radiation therapy, and a left-sided pulmonary malignancy.
View details for Web of Science ID 000248548700016
View details for PubMedID 17667039
High-risk repair of ascending aortic aneurysm due to giant cell aortitis.
Asian cardiovascular & thoracic annals
2007; 15 (3): 252-254
Giant cell arteritis increases the risk of developing a thoracic aortic aneurysm. Thoracic aortic aneurysm repair in octogenarians carries a profound increase in postoperative morbidity and mortality. We report the successful repair of an ascending aortic aneurysm in an 83-year-old woman with a history of treatment for temporal arteritis and pathologic evidence of giant cell aortitis.
View details for PubMedID 17541000
Myocardial regeneration therapy for ischemic cardiomyopathy with cyclin A2
86th Annual Meeting of the American-Association-for-Thoracic-Surgery
MOSBY-ELSEVIER. 2007: 927–33
Heart failure therapies ranging from revascularization to remodeling to replacement are variably effective. Theoretically, endogenous repair via myocardial regeneration would be an ideal therapy. This study examined the ability to initiate regeneration by adenoviral-mediated expression of the cell cycle regulator cyclin A2. Our prior studies have demonstrated robust cyclin A2 transgene expression and marked antiphosphorylated histone H3 activity with this strategy, indicating the induction of cardiomyocyte mitosis.Adult male, Lewis rats underwent left anterior descending coronary artery ligation followed by intramyocardial delivery of either cyclin A2 adenoviral vector (n = 8) or empty adeno-null vector as a control (n = 8) into the peri-infarct border zone. In vivo myocardial function was analyzed by echocardiography and invasive left ventricular pressure catheter at 6 weeks, when the animals are traditionally in heart failure. Hearts were explanted for immunoblotting and left ventricular geometric analysis. Cellular proliferation was assessed by proliferating cellular nuclear antigen expression.Cyclin A2 hearts exhibited improved left ventricular function as compared with controls including enhanced cardiac output (32 +/- 3.3 vs 26 +/- 5.0 mL/min, P < .05), stroke volume (0.16 +/- 0.04 vs 0.11 +/- 0.04 mL, P < .05), ejection fraction (72% +/- 7.4% vs 46.% +/- 8.5%, P < .05), fractional shortening (35% +/- 5.4% vs 19% +/- 4.3%, P < .002), maximum pressure (72 +/- 9.3 vs 61 +/- 2.9 mm Hg, P < .05), and end-systolic pressure (67 +/- 7.0 vs 55 +/- 7.0 mm Hg, P < .05). Enhanced myocardial preservation was demonstrated by enhanced left ventricular border zone wall thickness. Increased myocardial proliferation was evidenced by increased expression of proliferating cell nuclear antigen expression in cyclin A2-treated hearts.In failing hearts, targeted delivery of cyclin A2 improves hemodynamic function, as measured by echocardiography and pressure catheter analysis, preserves ventricular wall thickness, and may serve as an ideal myocardial regenerative therapy.
View details for DOI 10.1016/j.jtcvs.2006.07.057
View details for Web of Science ID 000245118100013
View details for PubMedID 17382628
Integrity of the cerebral blood-flow response to hyperoxia after cardiopulmonary bypass
JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA
2007; 21 (2): 212-217
In this study, the hypothesis that cardiopulmonary bypass (CPB) alters the cerebral blood flow (CBF) vasoconstrictive response to hyperoxia was tested.A prospective, observational study was conducted.The study was conducted at a single university hospital.Subjects were patients who presented for cardiac surgery with CPB.CBF was measured before and after CPB in 12 subjects while breathing 21% O(2) and 100% O(2). CBF was measured by using continuous arterial spin labeling (CASL) perfusion magnetic resonance imaging. Arterial pO(2) (mmHg), pCO(2) (mmHg), hemoglobin (Hgb), and oxygen content (CaO(2)) were also measured.Mean age of the 12 subjects was 63 +/- 16 years. Hgb decreased from 12.0 (+/-2.4) g/dL to 9.2 (+/-2.9) g/dL postoperatively (p = 0.008). CBF increased by 39%, from 37.2 (+/-10.8) mL/100 g/min to 49.2 (+/-14.3)mL/100 g/min postoperatively (p = 0.01). In response to the hyperoxic challenge CBF decreased by 8.0 (+/-7.1) mL/100 g/min (21%) preoperatively and by 9.4 (+/-6.4) mL/100 g/min (19%) postoperatively (p = 0.58). By using multiple regression, the contribution of CPB to the hyperoxic CBF response (DeltaCBF) was evaluated, while controlling for other potentially important covariates known to influence CBF, including age, baseline CBF on 21% O(2), and changes in arterial pO(2), pCO(2), and CaO(2). CPB state was not found to be a significant covariate in controlling the CBF response to hyperoxia.CPB does not impair the CBF response to hyperoxia.
View details for DOI 10.1053/j.jvca.2006.02.017
View details for Web of Science ID 000245872800009
View details for PubMedID 17418734
Ischemic heart failure enhances endogenous myocardial apelin and APJ receptor expression
CELLULAR & MOLECULAR BIOLOGY LETTERS
2007; 12 (1): 127-138
Apelin interacts with the APJ receptor to enhance inotropy. In heart failure, apelin-APJ coupling may provide a means of enhancing myocardial function. The alterations in apelin and APJ receptor concentrations with ischemic cardiomyopathy are poorly understood. We investigated the compensatory changes in endogenous apelin and APJ levels in the setting of ischemic cardiomyopathy.Male, Lewis rats underwent LAD ligation and progressed into heart failure over 6 weeks. Corresponding animals underwent sham thoracotomy as control. Six weeks after initial surgery, the animals underwent hemodynamic functional analysis in the presence of exogenous apelin-13 infusion and the hearts were explanted for western blot and enzyme immunoassay analysis. Western blot analysis of myocardial APJ concentration demonstrated increased APJ receptor protein levels with heart failure (1890750+/-133500 vs. 901600+/-143120 intensity units, n=8, p=0.00001). Total apelin protein levels increased with ischemic heart failure as demonstrated by enzyme immunoassay (12.0+/-4.6 vs. 1.0+/-1.2 ng/ml, n=5, p=0.006) and western blot (1579400+/-477733 vs. 943000+/-157600 intensity units, n=10, p=0.008). Infusion of apelin-13 significantly enhanced myocardial function in sham and failing hearts. We conclude that total myocardial apelin and APJ receptor levels increase in compensation for ischemic cardiomyopathy.
View details for DOI 10.2478/s11658-006-0058-7
View details for Web of Science ID 000244632300011
View details for PubMedID 17119870
Minimally invasive valve surgery.
Seminars in thoracic and cardiovascular surgery
2007; 19 (4): 289-298
As alternatives to standard sternotomy, surgeons have developed innovative, minimally invasive approaches to conducting valve surgery. Through very small skin incisions and partial upper sternal division for aortic valve surgery and right minithoracotomy for mitral surgery, surgeons have become adept at performing complex valve procedures. Beyond cosmetic appeal, apparent benefits range from decreased pain and bleeding to improved respiratory function and recovery time. The large retrospective studies and few small prospective randomized studies are herein briefly summarized. The focus is then directed toward describing specific intraoperative technical details in current clinical use, covering anesthetic preparation, incision, mediastinal access, cardiovascular cannulation, valve exposure, and valve reconstruction. Finally, unique situations such as pulmonic valve surgery, reoperations, beating heart surgery, and robotics are discussed.
View details for DOI 10.1053/j.semtcvs.2007.10.005
View details for PubMedID 18395627
Minimally invasive aortic valve papillary fibroelastoma resection.
Interactive cardiovascular and thoracic surgery
2006; 5 (6): 779-781
The standard approach to the resection of aortic valve papillary fibroelastoma has involved traditional full median sternotomy. In this case series, we demonstrate a minimally invasive approach to the resection of these cardiac tumors to decrease operative trauma, reduce postoperative bleeding, decrease pulmonary complications, and expedite recovery from surgery. All patients recovered without incident.
View details for PubMedID 17670711
Placental growth factor provides a novel local angiogenic therapy for ischemic cardiomyopathy
JOURNAL OF CARDIAC SURGERY
2006; 21 (6): 559-564
Heart failure occurs predominantly due to coronary artery disease and may be amenable to novel revascularization therapies. This study evaluated the effects of placental growth factor (PlGF), a potent angiogenic agent, in a rat model of ischemic cardiomyopathy.Wistar rats underwent high proximal ligation of the left anterior descending coronary artery and direct injection of PlGF (n = 10) or saline as a control (n = 10) into the myocardium bordering the ischemic area. After 2 weeks, the following parameters were evaluated: ventricular function with an aortic flow probe and a pressure/volume conductance catheter, left ventricular (LV) geometry by histology, and angiogenesis by immunofluorescence.PlGF animals had increased angiogenesis compared to controls (22.8 +/- 3.5 vs. 12.4 +/- 3.2 endothelial cells/high-powered field, p < 0.03). PlGF animals had less ventricular cavity dilation (LV diameter 8.4 +/- 0.2 vs. 9.2 +/- 0.2 mm, p < 0.03) and increased border zone wall thickness (1.85 +/- 0.1 vs. 1.38 +/- 0.2 mm, p < 0.03). PlGF animals had improved cardiac function as measured by maximum LV pressure (95.7 +/- 4 vs. 73.7 +/- 2 mmHg, p = 0.001), maximum dP/dt (4206 +/- 362 vs. 2978 +/- 236 mmHg/sec, p = 0.007), and ejection fraction (25.7 +/- 2 vs. 18.6 +/- 1%, p = 0.02).Intramyocardial delivery of PlGF following a large myocardial infarction enhanced border zone angiogenesis, attenuated adverse ventricular remodeling, and preserved cardiac function. This therapy may be useful as an adjunct or alternative to standard revascularization techniques in patients with ischemic heart failure.
View details for DOI 10.1111/j.1540-8191.2006.00296.x
View details for Web of Science ID 000241625300007
View details for PubMedID 17073953
Techniques for preserving vertebral artery perfusion during thoracic aortic stent grafting requiring aortic arch landing.
Vascular and endovascular surgery
2006; 40 (5): 367-373
Thoracic endografting offers many advantages over open repair. However, delivery of the device can be difficult and may necessitate adjunctive procedures. We describe our techniques for preserving perfusion to the left subclavian artery despite endograft coverage to obtain a proximal seal zone. We reviewed our experience with the Talent thoracic stent graft (Medtronic, Santa Rosa, CA). From 1999 to 2003, 49 patients received this device (29 men, 20 women). Seventeen patients required adjunctive procedures to facilitate proximal graft placement. We performed left subclavian-to-left common carotid artery transposition (6), left common carotid-to-left subclavian artery bypass with ligation proximal to the vertebral artery (7), and left common carotid-to-left subclavian artery bypass with proximal coil embolization (4). Patients who had anatomy unfavorable to transposition or bypass with proximal ligation (large aneurysms or proximal vertebral artery origin) were treated with coil embolization of the proximal left subclavian artery in order to prevent subsequent type II endoleaks. Technical success rate of the carotid subclavian bypass was 100%. Patient follow-up ranged from 3 to 48 months with a mean of 12 months. Six patients had follow-up <6 months owing to recent graft placement. Primary patency was 100%. No neurologic events occurred during the procedure or upon follow-up. One patient had a transient chyle leak that spontaneously resolved in 24 hours. Another patient had a phrenic nerve paresis that resolved after 3 weeks. We believe that it is important to maintain patency of the vertebral artery specifically when a patent right vertebral system and an intact basilar artery is not demonstrated. Furthermore, we describe a novel technique of coil embolization of the proximal left subclavian artery in conjunction with left common carotid-to-left subclavian artery bypass. This circumvents the need for potentially hazardous mediastinal dissection and ligation of the proximal left subclavian artery in cases of large proximal aneurysms or unfavorable vertebral artery anatomy.
View details for PubMedID 17038570
Combined DOR ventriculoplasty and aortic valve replacement in the treatment of post infarction ventricular aneurysm and aortic regurgitation
JOURNAL OF CARDIAC SURGERY
2006; 21 (5): 486-488
There has been only one other case of endoventricular circular patch plasty performed in conjunction with aortic valve replacement reported in the literature. We present the unique case of a patient suffering from congestive heart failure due to both post-infarct aortic regurgitation and ventricular aneurysm along with his successful surgical treatment.
View details for DOI 10.1111/j.15408191.2006.00305.x
View details for Web of Science ID 000240029300014
View details for PubMedID 16948765
Robotic cardiac surgery
INTERNATIONAL JOURNAL OF MEDICAL ROBOTICS AND COMPUTER ASSISTED SURGERY
2006; 2 (3): 225-232
Cardiac surgery, traditionally conducted via median sternotomy, has been recently forwarded by progressively advanced technology facilitating sternal-sparing minimally invasive, access to the heart. Robotic systems, comprised of miniaturized surgical instruments mounted on long thin shafts with multiple degrees of range of motion coupled with a dual camera endoscope providing true three-dimentional high-magnification visualization have greatly propelled this field.The robotic system and the literature base pertaining to robotic cardiac surgery is reviewed in depth.Robotic cardiac surgical procedures have been performed to repair and replace the mitral valve, bypass coronary arteries, close atrial septal defects, implant left ventricular pacing leads, and resect intracardiac tumors.As minimally invasive and robotic surgical technology advances, so proceeds the spectrum of potential applications for robotic cardiac surgery.
View details for DOI 10.1002/rcs.98
View details for Web of Science ID 000241078300004
View details for PubMedID 17520636
Robotic minimally invasive mitral valve reconstruction yields less blood product transfusion and shorter length of stay
67th Annual Meeting of the Society-of-University-Surgeons/1st Annual Academic Surgical Congress
MOSBY-ELSEVIER. 2006: 263–67
Robotic-assisted minimally invasive mitral valve reconstruction has gained popularity recently. Initial reports suggest that this approach can be used with relative safety and efficacy. Direct comparisons with a traditional sternotomy approach have not yet been explored extensively.All mitral valve procedures that were performed by a single surgeon during a 3-year period of time were analyzed (n = 142 procedures). Patients whose condition required concomitant coronary artery bypass grafting or aortic valve surgery were excluded subsequently from analysis, because all of these patients were approached obligatorily by sternotomy (n = 71 patients). Six patients underwent right thoracotomy mitral valve procedures without robotic assistance, and 1 patient in cardiogenic shock underwent emergent mitral valve reconstruction by sternotomy. Of the remaining 64 patients who were eligible theoretically for sternotomy or robotic-assisted minimally invasive surgery, 39 patients underwent sternotomy, and 25 patients underwent right chest minimally invasive robotic-assisted surgery. Randomization between these 2 approaches would be almost impossible in the United States. The primary determinant for the choice of approach was request of the referring physician or patient. Multiple perioperative outcomes were then compared.Patients who underwent sternotomy and robotic-assisted surgery exhibited equivalent preoperative characteristics and experienced an equivalent degree of correction of mitral regurgitation in repairs and in need for replacement. Complex mitral valve repairs that entailed leaflet resection and reapproximation, annular plication, sliding annuloplasty, chordal transfer, and GoreTex neochordal construction were accomplished successfully with the robotic system. Cross-clamp and bypass times were longer for patients in the minimally invasive group (110 vs 151 minutes; P = .0015; 162 vs 239 minutes; P < .001, respectively). Mean packed red blood cell transfusion was lower among patients who underwent robotic-assisted surgery (5.0 vs 2.8 units; P = .04). Patients who underwent robotic-assisted surgeries experienced shorter mean duration of postoperative hospitalization (10.6 vs 7.1 days; P = .04). There was 1 death among the patients who underwent sternotomy, and no deaths among the patients who underwent robotic-assisted surgery.Patients can undergo mitral valve reconstruction with minimally invasive robotic assistance, avoid a sternotomy, require less blood product transfusion, and experience shorter hospitalization.
View details for DOI 10.1016/j.surg.2006.05.003
View details for Web of Science ID 000240043200018
View details for PubMedID 16904978
Off-pump revascularization for significant left ventricular dysfunction.
Asian cardiovascular & thoracic annals
2006; 14 (4): 306-309
Left ventricular dysfunction is a predictor of perioperative morbidity and mortality in on-pump coronary artery bypass grafting. Obligatory global myocardial ischemia and injury induced during crossclamping as well as adverse systemic effects of cardiopulmonary bypass may induce a disproportionately greater overall physiologic insult in patients with poor ventricular function. All patients undergoing nonemergency off-pump coronary artery bypass by a single surgeon during an 18-month period were retrospectively analyzed. Two groups with preoperative ejection fraction classified as poor (10%-35%; n = 31) or normal (55%-80%; n = 60) were compared. The mean ejection fractions were 26% +/- 1% and 63% +/- 1% respectively, p < 0.000001. In those with significant left ventricular dysfunction, there were 2.8 +/- 0.1 grafts per patient, time to extubation was 8.4 +/- 1.2 hours, and discharge was after 4.9 +/- 0.6 days. These results were statistically equivalent to those in the group with normal left ventricular function. There was no intraaortic balloon pump insertion or mortality in either group. This technique provides an effective means of safely revascularizing patients with significant left ventricular dysfunction, and it may provide a valuable alternative approach in patients with ischemic cardiomyopathy.
View details for PubMedID 16868104
Therapeutic delivery of cyclin A2 induces myocardial regeneration and enhances cardiac function in ischemic heart failure
78th Annual Scientific Session of the American-Heart-Association
LIPPINCOTT WILLIAMS & WILKINS. 2006: I206–I213
Heart failure is a global health concern. As a novel therapeutic strategy, the induction of endogenous myocardial regeneration was investigated by initiating cardiomyocyte mitosis by expressing the cell cycle regulator cyclin A2.Lewis rats underwent left anterior descending coronary artery ligation followed by peri-infarct intramyocardial delivery of adenoviral vector expressing cyclin A2 (n =32) or empty adeno-null (n =32). Cyclin A2 expression was characterized by Western Blot and immunohistochemistry. Six weeks after surgery, in vivo myocardial function was analyzed using an ascending aortic flow probe and pressure-volume catheter. DNA synthesis was analyzed by proliferating cell nuclear antigen (PCNA), Ki-67, and BrdU. Mitosis was analyzed by phosphohistone-H3 expression. Myofilament density and ventricular geometry were assessed. Cyclin A2 levels peaked at 2 weeks and tapered off by 4 weeks. Borderzone cardiomyocyte cell cycle activation was demonstrated by increased PCNA (40.1+/-2.6 versus 9.3+/-1.1; P<0.0001), Ki-67 (46.3+/-7.2 versus 20.4+/-6.0; P<0.0001), BrdU (44.2+/-13.7 versus 5.2+/-5.2; P<0.05), and phosphohistone-H3 (12.7+/-1.4 versus 0+/-0; P<0.0001) positive cells/hpf. Cyclin A2 hearts demonstrated increased borderzone myofilament density (39.8+/-1.1 versus 31.8+/-1.0 cells/hpf; P=0.0011). Borderzone wall thickness was greater in cyclin A2 hearts (1.7+/-0.4 versus 1.4+/-0.04 mm; P<0.0001). Cyclin A2 animals manifested improved hemodynamics: Pmax (70.6+/-8.9 versus 60.4+/-11.8 mm Hg; P=0.017), max dP/dt (3000+/-588 versus 2500+/-643 mm Hg/sec; P<0.05), preload adjusted maximal power (5.75+/-4.40 versus 2.75+/-0.98 mWatts/microL2; P<0.05), and cardiac output (26.8+/-3.7 versus 22.7+/-2.6 mL/min; P=0.004).A therapeutic strategy of cyclin A2 expression via gene transfer induced cardiomyocyte cell cycle activation yielded increased borderzone myofilament density and improved myocardial function. This approach of inducing endogenous myocardial regeneration provides proof-of-concept evidence that cyclin A2 may ultimately serve as an efficient, alternative therapy for heart failure.
View details for DOI 10.1161/CIRCULATIONAHA.105.000455
View details for Web of Science ID 000238688200034
View details for PubMedID 16820573
Minimally invasive, robotic, and off-pump mitral valve surgery.
Seminars in thoracic and cardiovascular surgery
2006; 18 (2): 139-147
A significant transformation is occurring in the management of mitral valve disease. Earlier surgery is now recommended. Mitral valve repair is the standard of care, and newer methods of reconstructing the mitral valve are developing. Surgery with videoscopic assistance can be effectively performed without sternotomy. Robotics systems are gaining wider adoption. Implantable devices to repair or replace the mitral valve off-pump and percutaneously are emerging.
View details for PubMedID 17157235
Clinically silent cerebral ischemic events after cardiac surgery: Their incidence, regional vascular occurrence, and procedural dependence
ANNALS OF THORACIC SURGERY
2006; 81 (6): 2160-2166
The reported frequency of stroke after coronary artery bypass grafting varies between 1.5% and 6%, approaches 10% after aortic valve replacement, and may occur in between 40 to 70% in high-risk groups. Clinically silent infarction may be far more frequent and could contribute to long-term cognitive dysfunction in patients after cardiac procedures. Using diffusion-weighted magnetic resonance imaging we document the occurrence, vascular distribution, and procedural dependence of silent infarction after cardiac surgery with cardiopulmonary bypass. We also document the association of preexisting white matter lesions with new postoperative ischemic lesions.Thirty-four patients underwent T2-weighted fluid attenuated inversion recovery and diffusion-weighted magnetic resonance imaging before and after cardiac surgery with cardiopulmonary bypass for coronary artery bypass grafting, aortic valve replacement, and mitral valve repair or replacement surgery. Images were evaluated by experienced neuroradiologists for number, size, and vascular distribution of lesions.Mean age of participants was 67 +/- 15 years. Imaging occurred before and 6 +/- 2 days after surgery. New cerebral infarctions were evident in 6 of 34 patients (18%), were often multiple, and in 67% of patients were clinically silent. The occurrence of new infarctions by surgical procedure was as follows: aortic valve replacement (2 of 6), coronary artery bypass grafting and aortic valve replacement (3 of 8), aortic valve replacement with root replacement (1 of 1), coronary artery bypass grafting and mitral valve repair or replacement (0 of 4), mitral valve repair or replacement (0 of 2), and isolated coronary artery bypass grafting (0 of 13). New infarction occurred in 6 of 15 (40%) of all procedures involving aortic valve replacement. The severity of preexisting white matter lesions trended toward predicting the occurrence of new lesions (p = 0.055).Diffusion-weighted imaging reveals new cerebral infarctions in nearly 40% of patients after aortic valve replacement.
View details for DOI 10.1016/j.athoracsur.2006.01.080
View details for Web of Science ID 000238027600032
View details for PubMedID 16731147
Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
2006; 290 (6): H2196-H2203
Cellular therapy for myocardial injury has improved ventricular function in both animal and clinical studies, though the mechanism of benefit is unclear. This study was undertaken to examine the effects of cellular injection after infarction on myocardial elasticity. Coronary artery ligation of Lewis rats was followed by direct injection of human mesenchymal stem cells (MSCs) into the acutely ischemic myocardium. Two weeks postinfarct, myocardial elasticity was mapped by atomic force microscopy. MSC-injected hearts near the infarct region were twofold stiffer than myocardium from noninfarcted animals but softer than myocardium from vehicle-treated infarcted animals. After 8 wk, the following variables were evaluated: MSC engraftment and left ventricular geometry by histological methods, cardiac function with a pressure-volume conductance catheter, myocardial fibrosis by Masson Trichrome staining, vascularity by immunohistochemistry, and apoptosis by TdT-mediated dUTP nick-end labeling assay. The human cells engrafted and expressed a cardiomyocyte protein but stopped short of full differentiation and did not stimulate significant angiogenesis. MSC-injected hearts showed significantly less fibrosis than controls, as well as less left ventricular dilation, reduced apoptosis, increased myocardial thickness, and preservation of systolic and diastolic cardiac function. In summary, MSC injection after myocardial infarction did not regenerate contracting cardiomyocytes but reduced the stiffness of the subsequent scar and attenuated postinfarction remodeling, preserving some cardiac function. Improving scarred heart muscle compliance could be a functional benefit of cellular cardiomyoplasty.
View details for DOI 10.1152/ajpheart.01017.2005
View details for Web of Science ID 000237419600009
View details for PubMedID 16473959
Left main coronary embolism.
journal of invasive cardiology
2006; 18 (6): 296-?
This is a case of a 58-year-old female with a history of mitral regurgitation who had undergone mitral valve repair and was readmitted in cardiogenic shock with pericardial effusion, and then developed an anterior ST-elevation myocardial infarction. Coronary angiography revealed an embolus in the left main artery which was treated with rheolytic thrombectomy. This represents an uncommon cause of acute myocardial infarction.
View details for PubMedID 16775900
Comparison of Coapsys annuloplasty and internal reduction mitral annuloplasty in the randomized treatment of functional ischemic mitral regurgitation: Impact on the left ventricle
31st Annual Meeting of the Western-Thoracic-Surgical-Association
MOSBY-ELSEVIER. 2006: 1095–98
Functional mitral regurgitation is associated with both annular and ventricular distortion. Aggressive reduction annuloplasty for functional mitral regurgitation acts primarily at the annulus, with variable impact on the left ventricle. The Coapsys device externally reshapes the left ventricle to correct functional mitral regurgitation. Left ventricular reshaping was analyzed in a randomized study.The RESTOR-MV study randomizes patients with coronary artery disease and functional mitral regurgitation to either reduction annuloplasty and coronary artery bypass grafting (the RA group) or Coapsys annuloplasty and bypass grafting (the CO group). The Coapsys device consists of epicardial pads connected by a cord. It was placed without cardiopulmonary bypass under echocardiographic guidance and sized to reduce annular dimension and improve leaflet coaptation. Internal reduction annuloplasty was performed by device placement. Intraoperative transesophageal echocardiograms were analyzed in 7 patients having reduction annuloplasty and 7 having Coapsys annuloplasty.Baseline mitral regurgitation (0-4 scale) was similar for the RA (3.0 +/- 0.6) and the CO groups (3.0 +/- 0.6). Intraoperative mitral regurgitation was reduced from 2.86 +/- 0.7 to 0.5 +/- 0.7 (P < .01 pre vs post) for the RA group and from 2.64 +/- 0.9 to 05 +/- 0.7 (P < .01 pre vs post) for the CO group. Annular anteroposterior diameter was reduced with both techniques: RA, 3.45 +/- 0.39 to 2.34 +/- 0.37 cm (P < .01 pre vs post); CO, 3.40 +/- 0.27 to 2.85 +/- 0.34 cm (P < .05 pre vs post). Long-axis dimensions were unchanged with both techniques. Short-axis dimensions measured at three levels were significantly reduced only in the CO patients: basal diameter 4.77 +/- 0.58 to 3.58 +/- 0.38 cm (P < .01 pre vs post); mid diameter 4.88 +/- 0.55 to 3.57 +/- 0.43 cm (P < .01 pre vs post); and apical diameter 4.39 +/- 0.46 to 3.38 +/- 0.34 cm (P < .01 pre vs post).Coapsys and reduction annuloplasty techniques both acutely reduce functional mitral regurgitation and annular dimension. The Coapsys device provided significantly greater left ventricular reshaping than did reduction annuloplasty. Further evaluation will assess the long-term valvular function and ventricular geometric stability associated with both techniques.
View details for DOI 10.1016/j.jtcvs.2005.11.046
View details for Web of Science ID 000237322500026
View details for PubMedID 16678595
Neovasculogenic therapy to augment perfusion and preserve viability in ischemic cardiomyopathy.
Annals of thoracic surgery
2006; 81 (5): 1728-1736
Ischemic cardiomyopathy is a global health concern with limited therapy. We recently described endogenous revascularization utilizing granulocyte-macrophage colony stimulating factor (GMCSF) to induce endothelial progenitor cell (EPC) production and intramyocardial stromal cell-derived factor-1alpha (SDF) as a specific EPC chemokine. The EPC-mediated neovascularization and enhancement of myocardial function was observed. In this study we examined the regional biologic mechanisms underlying this therapy.Lewis rats underwent left anterior descending coronary artery (LAD) ligation and developed ischemic cardiomyopathy over 6 weeks. Three weeks after ligation, the animals received either subcutaneous GMCSF and intramyocardial SDF injections or saline injections as control. Six weeks after LAD ligation circulating EPC density was studied by flow cytometry. Quadruple immunofluorescent vessel staining for mature, proliferating vasculature was performed. Confocal angiography was utilized to identify fluorescein lectin-lined vessels to assess perfusion. Ischemia reversal was studied by measuring myocardial adenosine triphosphate (ATP) levels. Myocardial viability was assayed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling detection of apoptosis and quantitation of myofilament density.The GMCSF/SDF therapy enhanced circulating leukocyte (13.1 +/- 4.5 x 10(6) vs 3.1 +/- 0.5 x 10(6)/cc, p = 0.001, n = 6) and EPC (14.2 +/- 6.6 vs 2.2 +/- 2.1/cc, p = 0.001, n = 6) concentrations. Tetraimmunofluorescent labeling demonstrated enhanced stable vasculature with this therapy (39.2 +/- 8.1 vs 25.4 +/- 5.1%, p = 0.006, n = 7). Enhanced perfusion was shown by confocal microangiography of borderzone lectin-labeled vessels (28.2 +/- 5.4 vs 11.5 +/- 3.0 vessels/high power field [hpf], p = 0.00001, n = 10). Ischemia reversal was demonstrated by enhanced cellular ATP levels in the GMCSF/SDF borderzone myocardium (102.5 +/- 31.0 vs 26.9 +/- 4.1 nmol/g, p = 0.008, n = 5). Borderzone cardiomyocyte viability was noted by decreased apoptosis (3.2 +/- 1.4% vs 5.4 +/- 1.0%, p = 0.004, n = 10) and enhanced cardiomyocyte density (40.0 +/- 5.6 vs 27.0 +/- 6 myofilaments/hpf, p = 0.01, n=10).Endogenous revascularization for ischemic cardiomyopathy utilizing GMCSF EPC upregulation and SDF EPC chemokinesis upregulates circulating EPCs, enhances vascular stability, and augments myocardial function by enhancing perfusion, reversing cellular ischemia, and increasing cardiomyocyte viability.
View details for PubMedID 16631663
Fructose 1,6-diphosphate administration attenuates post-ischemic ventricular dysfunction.
Heart, lung & circulation
2006; 15 (2): 119-123
Cardiomyocyte energy production during ischemia depends upon anaerobic glycolysis inefficiently yielding two ATP per glucose. Substrate augmentation with fructose 1,6-diphosphate (FDP) bypasses the ATP consuming steps of glucokinase and phosphofructokinase thus yielding four ATP per FDP. This study evaluated the impact of FDP administration on myocardial function after acute ischemia.Male Wistar rats, 250-300 g, underwent 30 min occlusion of the left anterior descending coronary artery followed by 30 min reperfusion. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of FDP or saline control. After 30 min reperfusion, myocardial function was evaluated with a left ventricular intracavitary pressure/volume conductance microcatheter. For bioenergetics studies, myocardium was isolated at 5 min of ischemia and assayed for ATP levels.Compared to controls (n=8), FDP animals (n=8) demonstrated significantly improved maximal left ventricular pressure (100.5+/-5.4 mmHg versus 69.1+/-1.9 mmHg; p<0.0005), dP/dt (5296+/-531 mmHg/s versus 2940+/-175 mmHg/s; p<0.0028), ejection fraction (29.1+/-1.7% versus 20.4+/-1.4%; p<0.0017), and preload adjusted maximal power (59.3+/-5.0 mW/microL(2) versus 44.4+/-4.6 mW/microL(2); p<0.0477). Additionally, significantly enhanced ATP levels were observed in FDP animals (n=5) compared to controls (n=5) (535+/-156 nmol/g ischemic tissue versus 160+/-9.0 nmol/g ischemic tissue; p<0.0369).The administration of the glycolytic intermediate, FDP, by intravenous injection, resulted in significantly improved myocardial function after ischemia and improved bioenergetics during ischemia.
View details for PubMedID 16469539
Safety and efficacy of left ventricular assist device support in postmyocardial infarction cardiogenic shock
52nd Annual Meeting of the Southern-Thoracic-Surgical-Association
ELSEVIER SCIENCE INC. 2006: 1365–71
Cardiogenic shock secondary to acute myocardial infarction (CS-AMI) is the leading cause of death in all acute coronary syndromes. Experience with the use of left ventricular assist devices (LVADs) in patients with CS-AMI is limited. One of the surgical dilemmas when implanting an LVAD into a patient with an acute anterior wall myocardial infarction is the safety of apical cannulation. We present a decade of experience with the use of LVAD with apical cannulation in patients with CS-AMI.A retrospective review of the ventricular assist device (VAD) database at the Hospital of the University of Pennsylvania was instituted.From April 1995 to February 2005, 49 patients received LVAD support for CS-AMI (group I). The majority of these patients suffered anterior wall myocardial infarctions. This group of patients was compared with a separate cohort of 61 patients with chronic ischemic cardiomyopathy who received LVAD support (group II). The VAD support successfully bridged 38 (74%) group I patients and 37 (61%) group II patients to heart transplantation. Of the 38 patients transplanted in group I, 33 (87%) were discharged from the hospital. In group II, 36 of the 37 patients transplanted (97%) survived to hospital discharge. The overall in-hospital mortality rates for the series were 33% for group I patients, and 41% for group II patients.Left ventricular assist device support in patients with CS-AMI is a safe and effective therapy which should be incorporated into the standard treatment paradigm for appropriate patients presenting with this lethal disease.
View details for DOI 10.1016/j.athoracsur.2005.11.040
View details for Web of Science ID 000236239200030
View details for PubMedID 16564274
Neurological monitoring and off-pump surgery in a very high-risk stroke patient
ANNALS OF THORACIC SURGERY
2005; 80 (6): 2372-2374
Stroke remains a high risk of coronary artery bypass grafting. We present a patient with progressively symptomatic coronary disease and severe four-vessel cerebrovascular disease not amenable to revascularization. This patient underwent coronary revascularization without neurologic complication using off-pump coronary surgery to avoid aortic manipulation and intraoperative electroencephalographic monitoring of cerebral perfusion. This management strategy may reduce the stroke risk in similar patients.
View details for DOI 10.1016/j.athoracsur.2004.06.064
View details for Web of Science ID 000233926800070
View details for PubMedID 16305918
Intraoperative effects of the coapsys annuloplasty system in a randomized evaluation (RESTOR-MV) of functional ischemic mitral regurgitation
ANNALS OF THORACIC SURGERY
2005; 80 (5): 1706-1711
Functional ischemic mitral regurgitation (MR) frequently arises after myocardial infarction; it is characterized by annular enlargement or lateral displacement of the subvalvular apparatus. Coapsys is a ventricular-annular remodeling device designed to treat functional ischemic MR; it does not require cardiopulmonary bypass. Initial intraoperative results of the RESTOR-MV randomized clinical trial are presented.Patients referred for coronary artery bypass grafting with preoperative MR grade of 2 or greater were studied, excluding those with structural valve abnormalities. The Coapsys device, which consists of two epicardial pads connected by a flexible cord, was surgically implanted in 19 patients. Under epicardial echocardiographic guidance, the cord was passed through the left ventricle and tightened externally to improve leaflet coaptation and stabilize the ventricular wall; tightening was conducted with color flow Doppler imaging.Patients were 64.5 +/- 9.2 years old with an ejection fraction of 0.383 +/- 0.089 and received 2.7 +/- 1.1 grafts. Intraoperative MR grade was 2.7 +/- 0.8 after induction and was reduced to 0.4 +/- 0.7 after implantation (p < 0.0001). Mean epicardial dimension was reduced from 8.5 +/- 1.2 to 6.4 +/- 0.9 cm (p < 0.0001). Intraoperative MR was reduced in 95% (18 of 19) of patients, and 84% (16 of 19) had MR grade 1 or less after implantation. All implants were performed without cardiopulmonary bypass or conversion to standard annuloplasty. No hemodynamic compromise or structural damage to the mitral apparatus was noted. Significant acute remodeling was noted in the left ventricular dimensions.In patients without structural valve disease, the Coapsys device acutely reduces functional MR. Further randomized evaluation will assess long-term stability and compare it with standard annuloplasty techniques.
View details for DOI 10.1016/j.athoracsur.2005.04.034
View details for Web of Science ID 000232970500022
View details for PubMedID 16242443
Robotic resection of an aortic valve papillary fibroelastoma
ANNALS OF THORACIC SURGERY
2005; 80 (3): 1100-1102
Robotic technology has been applied to multiple cardiac surgical procedures. Purported benefits include decreased tissue trauma, reduced postoperative bleeding, fewer blood product transfusions, and shorter lengths of stay. We describe the case of a 50-year-old man with an incidentally discovered 1-cm mobile mass on the edge of the aortic valve noncoronary leaflet. The patient underwent robotic minimally invasive resection. The pathologic examination revealed papillary fibroelastoma.
View details for DOI 10.1016/j.athoracsur.2004.02.108
View details for Web of Science ID 000231683700056
View details for PubMedID 16122498
Stromal cell-derived factor and granulocyte-monocyte colony-stimulating factor form a combined neovasculogenic therapy for ischemic cardiomyopathy
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
2005; 130 (2): 321-329
Ischemic heart failure is an increasingly prevalent global health concern with major morbidity and mortality. Currently, therapies are limited, and novel revascularization methods might have a role. This study examined enhancing endogenous myocardial revascularization by expanding bone marrow-derived endothelial progenitor cells with the marrow stimulant granulocyte-monocyte colony-stimulating factor and recruiting the endothelial progenitor cells with intramyocardial administration of the potent endothelial progenitor cell chemokine stromal cell-derived factor.Ischemic cardiomyopathy was induced in Lewis rats (n = 40) through left anterior descending coronary artery ligation. After 3 weeks, animals were randomized into 4 groups: saline control, granulocyte-monocyte colony-stimulating factor only (GM-CSF only), stromal cell-derived factor only (SDF only), and combined stromal cell-derived factor/granulocyte-monocyte colony-stimulating factor (SDF/GM-CSF) (n = 10 each). After another 3 weeks, hearts were analyzed for endothelial progenitor cell density by endothelial progenitor cell marker colocalization immunohistochemistry, vasculogenesis by von Willebrand immunohistochemistry, ventricular geometry by hematoxylin-and-eosin microscopy, and in vivo myocardial function with an intracavitary pressure-volume conductance microcatheter.The saline control, GM-CSF only, and SDF only groups were equivalent. Compared with the saline control group, animals in the SDF/GM-CSF group exhibited increased endothelial progenitor cell density (21.7 +/- 3.2 vs 9.6 +/- 3.1 CD34 + /vascular endothelial growth factor receptor 2-positive cells per high-power field, P = .01). There was enhanced vascularity (44.1 +/- 5.5 versus 23.8 +/- 2.2 von Willebrand factor-positive vessels per high-power field, P = .007). SDF/GM-CSF group animals experienced less adverse ventricular remodeling, as manifested by less cavitary dilatation (9.8 +/- 0.1 mm vs 10.1 +/- 0.1 mm [control], P = .04) and increased border-zone wall thickness (1.78 +/- 0.19 vs 1.41 +/- 0.16 mm [control], P = .03). (SDF/GM-CSF group animals had improved cardiac function compared with animals in the saline control group (maximum pressure: 93.9 +/- 3.2 vs 71.7 +/- 3.1 mm Hg, P < .001; maximum dP/dt: 3513 +/- 303 vs 2602 +/- 201 mm Hg/s, P < .05; cardiac output: 21.3 +/- 2.7 vs 13.3 +/- 1.3 mL/min, P < .01; end-systolic pressure-volume relationship slope: 1.7 +/- 0.4 vs 0.5 +/- 0.2 mm Hg/microL, P < .01.)This novel revascularization strategy of bone marrow stimulation and intramyocardial delivery of the endothelial progenitor cell chemokine stromal cell-derived factor yielded significantly enhanced myocardial endothelial progenitor cell density, vasculogenesis, geometric preservation, and contractility in a model of ischemic cardiomyopathy.
View details for DOI 10.1016/j.jtcvs.2004.11.041
View details for Web of Science ID 000231069700015
View details for PubMedID 16077394
Robot-assisted pharyngeal and laryngeal microsuirgery: Results of robotic cadaverb dissections
Annual Meeting of the Triologic-Society
JOHN WILEY & SONS INC. 2005: 1003–8
Robotic surgery has significant potential in pharyngeal and microlaryngeal surgery. We demonstrate the use of a surgical robot in pharyngeal and microlaryngeal surgery in a cadaver.Six experimental surgical dissections, modeled after commonly performed pharyngeal and microlaryngeal procedures, were performed in a cadaver with a commercially available surgical robot in an operating room suite to demonstrate proof of concept.Using the daVinci Surgical Robot (Intuitive Surgical, Sunnyvale, CA), surgical procedures were performed on an edentulous, female cadaver. The procedures included 1) bilateral true vocal cord stripping, 2) rotation of a mucosal flap from the epiglottis to the anterior commissure, 3) partial vocal cordectomy, 4) arytenoidectomy, 5) partial epiglottectomy and thyrohyoid dissection and 6) partial resection of the base of tongue with primary closure. All procedures were timed and documented with still and video photography.The daVinci Surgical Robot, with currently available instruments, enabled performance of several laryngeal and pharyngeal surgical procedures on a cadaver. Laryngeal and pharyngeal exposure was excellent, instruments movement was unimpeded, tissue handling was delicate and precise, and endolaryngeal suturing was relatively easily performed. The duration of the different robotic cadaver dissections was comparable to procedure duration using conventional techniques.Using the daVinci Surgical Robot, six different pharyngeal and microlaryngeal dissections were successfully performed in a cadaver. The recent development of surgical robotics has a potential role in pharyngeal and microlaryngeal surgery. Surgical robots offer the ability to manipulate instruments at their distal ends with increased freedom of movement, scaled movement, tremor buffering, and under stereoscopic three-dimensional visualization. Surgical robots may increase the precision with which we perform currently described procedures; additionally, surgical robots may advance the field of endoscopic laryngeal and pharyngeal surgery.
View details for DOI 10.1212/01.WNL.0000164714.90354.7D
View details for Web of Science ID 000229682900014
View details for PubMedID 15933510
Creatine phosphate administration preserves myocardial function in a model of off-pump coronary revascularization
JOURNAL OF CARDIOVASCULAR SURGERY
2005; 46 (3): 297-303
Off pump coronary artery bypass grafting (OPCAB) involves, and is occasionally impaired by obligatory regional myocardial ischemia, particularly with the use of proximal coronary in-flow occlusion techniques. Intracoronary shunts do not guarantee absence of distal ischemia given their small inner diameter and the presence of proximal coronary stenosis. Additional adjunctive measures to provide short-term myocardial protection may facilitate OPCAB. High-energy phosphate supplementation with creatine phosphate prior to ischemia may attenuate ischemic dysfunction.In a rodent model of a transient coronary occlusion and myocardial ischemia, 36 animals underwent preischemic intravenous infusion of either creatine phosphate or saline, 10 minutes of proximal left anterior descending (LAD) occlusion, and 10 minutes of reperfusion. Rats underwent continuous intracavitary pressure monitoring and cellular ATP levels were quantified using a luciferin/luciferase bioluminescence assay.Within 2 minutes of ischemia onset, creatine phosphate animals exhibited statistically significant greater preservation of myocardial function compared to controls, an augmentation which persisted throughout the duration of ischemia and subsequent reperfusion. Furthermore, significantly greater cellular ATP levels were observed among creatine phosphate treated animals (344+/-55 nMol/g tissue, n=5) compared to control animals (160+/-9 nMol/g tissue, n=5)(p=0.014).A strategy of intravenous high-energy phosphate administration successfully prevented ischemic ventricular dysfunction in a rodent model of OPCAB.
View details for Web of Science ID 000231101300014
View details for PubMedID 15956929
Active thermoregulation improves outcome of off-pump coronary artery bypass.
Asian cardiovascular & thoracic annals
2005; 13 (2): 157-160
During off-pump coronary artery bypass grafting, hypothermia increases vasoconstriction, myocardial afterload, coagulopathy and postoperative bleeding. Traditional thermoregulatory techniques do not maintain core body temperature intraoperatively. The efficacy of a commercially available, computer-controlled, water-circulating, dorsal surface, active warming system for thermoregulatory control was evaluated. All patients who underwent non-emergency off-pump coronary bypass grafting by a single surgeon in a 1-year period were studied: the thermoregulation device was used in 50 cases and unavailable for use in 19. The patients who underwent active thermoregulation demonstrated significantly improved core body temperatures compared to the controls: lowest intraoperative, 35.8 degrees C +/- 0.1 degrees C vs. 35.0 degrees C +/- 0.2 degrees C; immediately postoperative, 36.5 degrees C +/- 0.1 degrees C vs. 35.6 degrees C +/- 0.2 degrees C; and 1-hour postoperative, 36.6 degrees C +/- 0.1 degrees C vs. 35.9 degrees C +/- 0.2 degrees C. Thermoregulated patients had significantly reduced 24-hour chest tube drainage (764 +/- 38 vs. 1227 +/- 183 mL), packed red blood cell transfusions (1.4 +/- 0.2 vs. 3.3 +/- 0.7 units), time to extubation (6.8 +/- 0.5 vs. 11.4 +/- 2.3 hours), intensive care unit stay (1.3 +/- 0.1 vs. 2.0 +/- 0.3 days), and hospital stay (4.3 +/- 0.1 vs. 5.1 +/- 0.3 days).
View details for PubMedID 15905346
Robotic microlaryngeal surgery: A technical feasibility study using the daVinci surgical robot and an airway mannequin
2005; 115 (5): 780-785
The trend toward minimally invasive surgery has led to the development and mastery of endoscopic and laparoscopic surgical techniques. These minimally invasive approaches, which only two decades ago were either novel or experimental, are now mainstream. More recently, robot-assisted surgery has evolved as an adjunct to open and endoscopic techniques. Surgical robots are now approved by the United States Food and Drug Administration for a variety of thoracic and abdominal/pelvic surgical procedures. The purpose of this study is to demonstrate the technical feasibility of robot-assisted microlaryngeal surgery.Experimental surgical manipulation of the larynx in an airway mannequin with a surgical robot.A variety of laryngoscopes and mouthgags, coupled with the daVinci Surgical Robot's (Intuitive Surgical, Sunnyvale, CA) 0-degree and 30-degree, two-dimensional and three-dimensional endoscopes, were utilized to optimize visualization of the larynx in an airway mannequin. Five millimeter and 8 mm microinstruments compatible with the daVinci robot were utilized to manipulate different elements of the larynx. Experiments were recorded with both still and video photography.The endoscope and robotic arms of the daVinci robot are well suited to airway surgery.Robot-assisted laryngeal surgery can be performed with currently available technology. The potential for fine manipulation of tissues, increased freedom of instrument movement, and endolaryngeal suturing may increase the precision of endoscopic laryngeal microsurgery and offers the potential to increase the variety of laryngeal procedures that can be performed endoscopically.
View details for Web of Science ID 000229047800006
View details for PubMedID 15867639
One year transgene expression with adeno-associated virus cardiac gene transfer
INTERNATIONAL JOURNAL OF CARDIOLOGY
2005; 100 (3): 421-426
Adeno-associated virus (AAV) has shown promise as a vector for cardiac gene transfer given its ability to stably integrate into the host genome and its lack of immune reactivity. This study examined the feasibility of AAV-mediated myocardial gene transfer in mice, the animal which, because of transgenic technology, has become the disease model of choice for cardiovascular research.AAV encoding the cytomegalovirus promoter driven LacZ reporter gene (10(7) LacZ-forming units per animal) or vehicle control was injected into the hearts of young adult C57Bl/6 mice by a transdiaphragmatic approach. At one, two, three, six, and twelve months post-injection, cardiac function was assessed by transthoracic echocardiography and hearts were assayed by X-gal histochemical staining.Echocardiography revealed normal left ventricular function in both AAV and control groups at all time points. X-gal staining of cryostat sections of hearts revealed uniform LacZ expression at all time points. There were minimal signs of immunologic infiltration by hematoxylin and eosin staining.AAV-mediated myocardial gene transfer by transdiaphragmatic injection can be conducted safely and results in long-term expression of the LacZ gene for at least one year without causing significant inflammatory response or adversely affecting LV systolic function.
View details for DOI 10.1016/j.ijcard.2004.09.003
View details for Web of Science ID 000228814600012
View details for PubMedID 15837086
Cardiac surgery in patients on antiplatelet and antithrombotic agents.
Seminars in thoracic and cardiovascular surgery
2005; 17 (1): 66-72
The widespread application of antithrombotic agents carries significant potential for inducing excessive peri-operative hemorrhage during cardiac surgery. Specific surgical and medical strategies can be employed to attenuate this bleeding. These antithrombotic agents and anti-hemorrhagic measures will be reviewed in depth.
View details for PubMedID 16104363
Ethyl pyruvate enhances ATP levels, reduces oxidative stress and preserves cardiac function in a rat model of off-pump coronary bypass.
Heart, lung & circulation
2005; 14 (1): 25-31
Off-pump coronary artery bypass grafting is associated with transient periods of myocardial ischemia during revascularization resulting in myocardial contractile dysfunction and oxidative injury. The purpose of this study was to investigate the efficacy of ethyl pyruvate as a myocardial protective agent in a rat model of off-pump coronary artery bypass grafting associated with transient myocardial dysfunction without infarction.Wistar rats were subjected to transient ischemia via 10 min occlusion of the LAD coronary artery followed by 10 min of reperfusion. Animals received an IV bolus of Ringer's solution as a control (n=10) or Ringer's ethyl pyruvate (n=10) immediately before the initiation of ischemia and reperfusion. Myocardial ATP and lipid peroxidation levels were quantified for an estimation of energetics and oxidative stress, respectively. In vivo cardiac function was assessed throughout the ischemia and reperfusion periods.Ethyl pyruvate significantly increased myocardial ATP levels compared to controls (2650+/-759 nmol/g versus 892+/-276 nmol/g, p=0.04). Myocardial oxidative stress was significantly reduced in animals treated with ethyl pyruvate compared to controls (70.4+/-2.6 nmol/g versus 81.8+/-2.4 nmol/g, p=0.04). dP/dt max and cardiac output were significantly greater in the ethyl pyruvate group compared to controls during ischemia and reperfusion.Ethyl pyruvate enhances myocardial ATP levels, reduces oxidative stress, and preserves myocardial function in a model of transient ischemia/reperfusion injury not subject to myocardial infarction.
View details for PubMedID 16352248
Minimally invasive aortic valve replacement combined with radiofrequency-modified maze procedure
JOURNAL OF CARDIAC SURGERY
2005; 20 (2): 164-166
The treatment of chronic atrial fibrillation undergoing concomitant cardiac surgery is gaining greater acceptance. This is the first reported case of a minimally invasive aortic valve replacement combined with a radiofrequency-modified maze procedure.
View details for Web of Science ID 000235710700011
View details for PubMedID 15725142
Induction of angiogenesis and inhibition of apoptosis by hepatocyt growth factor effectively treats postischemic heart failure
JOURNAL OF CARDIAC SURGERY
2005; 20 (1): 93-101
Heart failure following myocardial infarction (MI) is a significant cause of morbidity and mortality and remains a difficult therapeutic challenge. Hepatocyte growth factor (HGF) is a potent angiogenic and anti-apoptotic protein whose receptor is upregulated following MI. This study was designed to investigate the ability of HGF to prevent heart failure in a rat model of experimental MI.The rats underwent direct intramyocardial injection with replication-deficient adenovirus encoding HGF (n = 7) or null virus as control (n = 7) 3 weeks following ligation of the left anterior descending coronary artery. Analysis of the following was performed 3 weeks after injection: cardiac function by pressure-volume conductance catheter measurements; LV wall thickness; angiogenesis by Von Willebrand's factor staining; and apoptosis by the TUNEL assay. The expression levels of HGF and the anti-apoptotic factor Bcl-2 were analyzed by Western blot.Adeno-HGF-treated animals had greater preservation of maximum LV pressure (HGF 77 +/- 3 vs. control 64 +/- 5 mmHg, p < 0.05), maximum dP/dt (3024 +/- 266 vs. 1907 +/- 360 mmHg/sec, p < 0.05), maximum dV/dt (133 +/- 20 vs. 84 +/- 6 muL/sec, p < 0.05), and LV border zone wall thickness (1.98 +/- 0.06 vs. 1.53 +/- 0.07 mm, p < 0.005). Angiogenesis was enhanced (151 +/- 10.0 vs. 90 +/- 4.5 endothelial cells/hpf, p < 0.005) and apoptosis was reduced (3.9 +/- 0.3 vs. 8.2 +/- 0.5%, p < 0.005). Increased expression of HGF and Bcl-2 protein was observed in the Adeno-HGF-treated group.Overexpression of HGF 3 weeks post-MI resulted in enhanced angiogenesis, reduced apoptosis, greater preservation of ventricular geometry, and preservation of cardiac contractile function. This technique may be useful to treat or prevent postinfarction heart failure.
View details for Web of Science ID 000226958900019
View details for PubMedID 15673421
Targeted overexpression of leukemia inhibitory factor to preserve myocardium in a rat model of postinfarction heart failure
84th Annual Meeting of the American-Association-for-Thoracic-Surgery
MOSBY-ELSEVIER. 2004: 866–75
Myocardial infarction leads to cardiomyocyte loss. The cytokine leukemia inhibitory factor regulates the differentiation and growth of embryonic and adult heart tissue. This study examined the effects of gene transfer of leukemia inhibitory factor in infarcted rat hearts.Lewis rats underwent ligation of the left anterior descending coronary artery and direct injection of adenovirus encoding leukemia inhibitory factor (n = 10) or null transgene as control (n = 10) into the myocardium bordering the ischemic area. A sham operation group (n = 10) underwent thoracotomy without ligation. After 6 weeks, the following parameters were evaluated: cardiac function with a pressure-volume conductance catheter, left ventricular geometry and architecture by histologic methods; myocardial fibrosis by Masson trichrome staining, apoptosis by terminal deoxynucleotidal transferase-mediated deoxyuridine triphosphate nick-end labeling assay, and cardiomyocyte size by immunofluorescence.Rats with overexpression of leukemia inhibitory factor had more preserved myocardium and less fibrosis in both the infarct and its border zone. The border zone in leukemia inhibitory factor-treated animals contained fewer apoptotic nuclei (1.6% +/- 0.1% vs 3.3% +/- 0.2%, P < .05) than that in control animals and demonstrated cardiomyocytes with larger cross-sectional areas (910 +/- 60 microm 2 vs 480 +/- 30 microm 2 , P < .05). Leukemia inhibitory factor-treated animals had increased left ventricular wall thickness (2.1 +/- 0.1 mm vs 1.8 +/- 0.1 mm, P < .05) and less dilation of the left ventricular cavity (237 +/- 22 microL vs 301 +/- 16 microL, P < .05). They also had improved cardiac function, as measured by maximum change in pressure over time (3950 +/- 360 mm Hg/s vs 2750 +/- 230 mm Hg/s, P < .05) and the slopes of the maximum change in pressure over time-end-diastolic volume relationship (68 +/- 5 mm Hg/[s . microL] vs 46 +/- 6 mm Hg/[s . microL], P < .05) and the preload recruitable stroke work relationship (89 +/- 10 mm Hg vs 44 +/- 4 mm Hg, P < .05).Myocardial gene transfer of leukemia inhibitory factor preserved cardiac tissue, geometry, and function after myocardial infarction in rats.
View details for DOI 10.1016/j.jtcvs.2004.06.046
View details for Web of Science ID 000225475700012
View details for PubMedID 15573071
- Innominate artery transection in the setting of a bovine arch JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY 2004; 128 (4): 632-634
Inhibition of matrix metalloproteinase activity by TIMP-1 gene transfer effectively treats ischemic cardiomyopathy
2004; 110 (11): II180-II186
Enhanced activity of matrix metalloproteinases (MMPs) has been associated with extracellular matrix degradation and ischemic heart failure in animal models and human patients. This study evaluated the effects of MMP inhibition by gene transfer of TIMP-1 in a rat model of ischemic cardiomyopathy.Rats underwent ligation of the left anterior descending coronary artery with direct intramyocardial injection of replication-deficient adenovirus encoding TIMP-1 (n=8) or null virus as control vector (n=8), and animals were analyzed after 6 weeks. Both systolic and diastolic cardiac function was significantly preserved in the TIMP-1 group compared with control animals (maximum left ventricular [LV] pressure: TIMP-1 70+/-10 versus control 56+/-12 mmHg, P<0.05; maximum dP/dt 2697+/-842 versus 1622+/-527 mmHg/sec, P<0.01; minimum dP/dt -2900+/-917 versus -1195+/-593, P<0.001). Ventricular geometry was significantly preserved in the TIMP-1 group (LV diameter 13.0+/-0.7 versus control 14.4+/-0.4 mm, P<0.001; border-zone wall thickness 1.59+/-0.11 versus control 1.28+/-0.19 mm, P<0.05), and this was associated with a reduction in myocardial fibrosis (2.36+/-0.87 versus control 3.89+/-1.79 microg hydroxyproline/mg tissue, P<0.05). MMP activity was reduced in the TIMP-1 animals (1.5+/-0.9 versus control 43.1+/-14.9 ng of MMP-1 activity, P<0.05).TIMP-1 gene transfer inhibits MMP activity and preserves cardiac function and geometry in ischemic cardiomyopathy. The reduction in myocardial fibrosis may be primarily responsible for the improved diastolic function in treated animals. TIMP-1 overexpression is a promising therapeutic target for continued investigation.
View details for DOI 10.1161/01.CIR.0000138946.29375.49
View details for Web of Science ID 000224023600032
View details for PubMedID 15364860
Apelin has in vivo inotropic effects on normal and failing hearts
2004; 110 (11): II187-II193
Apelin has been shown ex vivo to be a potent cardiac inotrope. This study was undertaken to evaluate the in vivo effects of apelin on cardiac function in native and ischemic cardiomyopathic rat hearts using a novel combination of a perivascular flow probe and a conductance catheter.Native rats (n =32) and rats in heart failure 6 weeks after left anterior descending coronary artery ligation (n =22) underwent median sternotomy with placement of a perivascular flow probe around the ascending aorta and a pressure volume conductance catheter into the left ventricle. Compared with sham-operated rats, the ligated rats had significantly decreased baseline Pmax and max dP/dt. Continuous infusion of apelin at a rate of 0.01 microg/min for 20 minutes significantly increased Pmax and max dP/dt compared with infusion of vehicle alone in both native and failing hearts. Apelin infusion increased cardiac contractility, indicated by a significant increase in stroke volume (SV) without a change in left ventricular end diastolic volume (102+/-16% change from initial SV versus 26+/-20% for native animals, and 110+/-30% versus 26+/-11% for ligated animals), as well as an increase in preload recruitable stroke work (180+/-24 mm Hg versus 107+/-9 mm Hg for native animals).The present study is the first to show that apelin has positive inotropic effects in vivo in both normal rat hearts and rat hearts in failure after myocardial infarction. Apelin may have use as an acute inotropic agent in patients with ischemic heart failure.
View details for DOI 10.1161/01.CIR.0000138382.57325.5c
View details for Web of Science ID 000224023600033
View details for PubMedID 15364861
Administration of a tumor necrosis factor inhibitor at the time of myocardial infarction attenuates subsequent ventricular remodeling
JOURNAL OF HEART AND LUNG TRANSPLANTATION
2004; 23 (9): 1061-1068
Tumor necrosis factor (TNF) causes myocardial extracellular matrix remodeling and fibrosis in myocardial infarction and chronic heart failure models. Pre-clinical and clinical trials of TNF inhibition in chronic heart failure have shown conflicting results. This study examined the effects of the administration of a TNF inhibitor immediately after myocardial infarction on the development of heart failure.Lewis rats underwent coronary artery ligation and then received either intravenous etanercept (n = 14), a soluble dimerized TNF receptor that inhibits TNF, or saline as control (n = 13). Leukocyte infiltration into the infarct borderzone was evaluated 4 days post-ligation in 7 animals (etanercept = 4, control = 3). After 6 weeks, the following parameters were evaluated in the remaining animals: cardiac function with a pressure-volume conductance catheter, left ventricular (LV) geometry, and borderzone collagenase activity.Etanercept rats had significantly less borderzone leukocyte infiltration 4 days post-infarction than controls (10.7 +/- 0.5 vs 18.0, +/-2.0 cells/high power field; p < 0.05). At 6 weeks, TNF inhibition resulted in significantly reduced borderzone collagenase activity (110 +/- 30 vs 470 +/- 140 activity units; p < 0.05) and increased LV wall thickness (2.1 +/- 0.1 vs 1.8 +/- 0.1 mm, p < 0.05). Etanercept rats had better systolic function as measured by maximum LV pressure (84 +/- 3 mm Hg vs 68 +/- 5 mm Hg, p < 0.05) and the maximum change in left ventricular pressure over time (maximum dP/dt) (3,110 +/- 230 vs 2,260 +/- 190 mm Hg/sec, p < 0.05), and better diastolic function as measured by minimum dP/dt (-3,060 +/- 240 vs -1,860 +/- 230 mm Hg/sec; p < 0.05) and the relaxation time constant (14.6 +/- 0.6 vs 17.9 +/- 1.2 msec; p < 0.05).TNF inhibition after infarction reduced leukocyte infiltration and extracellular matrix turnover and preserved cardiac function.
View details for DOI 10.1016/j.healun.2004.06.021
View details for Web of Science ID 000224230300007
View details for PubMedID 15454172
Local myocardial overexpression of growth hormone attenuates postinfarction remodeling and preserves cardiac function
ANNALS OF THORACIC SURGERY
2004; 77 (6): 2122-2129
Ventricular remodeling with chamber dilation and wall thinning is seen in postinfarction heart failure. Growth hormone induces myocardial hypertrophy when oversecreted. We hypothesized that localized myocardial hypertrophy induced by gene transfer of growth hormone could inhibit remodeling and preserve cardiac function after myocardial infarction.Rats underwent direct intramyocardial injection of adenovirus encoding either human growth hormone (n = 9) or empty null vector as control (n = 9) 3 weeks after ligation of the left anterior descending coronary artery. Analysis of the following was performed 3 weeks after delivery: hemodynamics, ventricular geometry, cardiomyocyte fiber size, and serum growth hormone levels.The growth hormone group had significantly better systolic cardiac function as measured by maximum left ventricular pressure (73.6 +/- 6.9 mm Hg versus control 63.7 +/- 7.8 mm Hg, p < 0.05) and maximum dP/dt (2845 +/- 453 mm Hg/s versus 1949 +/- 605 mm Hg/s, p < 0.005), and diastolic function as measured by minimum dP/dt (-2520 +/- 402 mm Hg/s versus -1500 +/- 774 mm Hg/s, p < 0.01). Ventricular geometry was preserved in the growth hormone group (ventricular diameter 12.2 +/- 0.7 mm versus control 13.1 +/- 0.4 mm, p < 0.05; borderzone wall thickness 2.0 +/- 0.2 mm versus 1.5 +/- 0.1 mm, p < 0.001), and was associated with cardiomyocyte hypertrophy (6.09 +/- 0.63 microm versus 4.66 +/- 0.55 microm, p < 0.005). Local myocardial expression of growth hormone was confirmed, whereas serum levels were undetectable after 3 weeks.Local myocardial overexpression of growth hormone after myocardial infarction resulted in cardiomyocyte hypertrophy, attenuated ventricular remodeling, and improved systolic and diastolic cardiac function. The induction of localized myocardial hypertrophy presents a novel therapeutic approach for the treatment of ischemic heart failure.
View details for DOI 10.1016/j.athoracsur.2003.12.043
View details for Web of Science ID 000221717200039
View details for PubMedID 15172279
Ethyl pyruvate preserves cardiac function and attenuates oxidative injury after prolonged myocardial ischemia
83rd Annual Meeting of the American-Association-for-Thoracic-Surgery
MOSBY-ELSEVIER. 2004: 1262–69
Myocardial injury and dysfunction following ischemia are mediated in part by reactive oxygen species. Pyruvate, a key glycolytic intermediary, is an effective free radical scavenger but unfortunately is limited by aqueous instability. The ester derivative, ethyl pyruvate, is stable in solution and should function as an antioxidant and energy precursor. This study sought to evaluate ethyl pyruvate as a myocardial protective agent in a rat model of ischemia-reperfusion injury.Rats underwent 30-minute ischemia and 30-minute reperfusion of the left anterior descending coronary artery territory. Immediately prior to both ischemia and reperfusion, animals received an intravenous bolus of either ethyl pyruvate (n = 26) or vehicle control (n = 26). Myocardial high-energy phosphate levels were determined by adenosine triphosphate assay, oxidative injury was measured by lipid peroxidation assay, infarct size was quantified by triphenyltetrazolium chloride staining, and cardiac function was assessed in vivo.Ethyl pyruvate administration significantly increased myocardial adenosine triphosphate levels compared with control (87.6 +/- 29.2 nmol/g vs 10.0 +/- 2.4 nmol/g, P =.03). In ischemic myocardium, ethyl pyruvate reduced oxidative injury compared with control (63.8 +/- 3.3 nmol/g vs 89.5 +/- 3.0 nmol/g, P <.001). Ethyl pyruvate diminished infarct size as a percentage of area at risk (25.3% +/- 1.5% vs 33.6% +/- 2.1%, P =.005). Ethyl pyruvate improved myocardial function compared with control (maximum pressure: 86.6 +/- 2.9 mm Hg vs 73.5 +/- 2.5 mm Hg, P <.001; maximum rate of pressure rise: 3518 +/- 243 mm Hg/s vs 2703 +/- 175 mm Hg/s, P =.005; maximal rate of ventricular systolic volume ejection: 3097 +/- 479 microL/s vs 2120 +/- 287 microL/s, P =.04; ejection fraction: 41.9% +/- 3.8% vs 31.4% +/- 4.1%, P =.03; cardiac output: 26.7 +/- 0.9 mL/min vs 22.7 +/- 1.3 mL/min, P =.01; and end-systolic pressure-volume relationship slope: 1.09 +/- 0.22 vs 0.59 +/- 0.2, P =.02).In this study of myocardial ischemia-reperfusion injury, ethyl pyruvate enhanced myocardial adenosine triphosphate levels, attenuated myocardial oxidative injury, decreased infarct size, and preserved cardiac function.
View details for DOI 10.1016/j.jtcvs.2003.11.032
View details for Web of Science ID 000221134600006
View details for PubMedID 15115981
Targeted overexpression of growth hormone by adenoviral gene transfer preserves myocardial function and ventricular geometry in ischemic cardiomyopathy
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
2004; 36 (4): 531-538
Post-infarction heart failure is characterized by progressive left ventricular dilatation and wall thinning, with both systolic and diastolic cardiac dysfunction. Human growth hormone (GH) stimulates cardiac hypertrophy when secreted in excess and directly enhances cardiomyocyte contractile function. We hypothesized that local myocardial overexpression of GH could prevent ventricular remodeling and heart failure following myocardial infarction (MI) in rats.Rats underwent ligation of the left anterior descending coronary artery with direct intramyocardial injection of adenovirus encoding human GH (n = 8) or null virus as control (n = 8). Six weeks following MI, Adeno-GH treated animals had significant preservation of both systolic and diastolic cardiac function compared to Null animals (maximum dP/dt GH 2927 +/- 83 vs Null 1622 +/- 159 mmHg/sec, p < 0.001; minimum dP/dt -2409 +/- 82 vs -1195 +/- 179 mmHg/sec, p < 0.01). GH animals had improved ventricular geometry with decreased chamber dilatation (13.2 +/- 0.13 vs 14.4+/-0.15 mm, p < 0.001) and increased wall thickness (2.02 +/- 0.10 vs 1.28 +/- 0.07 mm, p < 0.001), and this was associated with advantageous myocardial hypertrophy with increased cardiomyocyte fiber size. Local myocardial overexpression of GH protein was seen in Adeno-GH animals, while serum levels of human GH were undetectable after 6 weeks.Treatment with Adeno-GH following MI resulted in reduced ventricular dilatation, increased local myocardial hypertrophy, and preservation of both systolic and diastolic cardiac function. No significant systemic exposure to growth hormone transgene was observed. The induction of regional hypertrophy is a novel approach to treating heart failure, and may be useful to treat or prevent post-infarction ischemic cardiomyopathy.
View details for DOI 10.1016/j.yjmcc.2004.01.010
View details for Web of Science ID 000221181400008
View details for PubMedID 15081312
Should Standard On-Pump Protamine Dosing Formulas Be Recalculated for Off-Pump Coronary Artery Bypass Grafting?
heart surgery forum
2004; 7 (1): 42-44
Abstract Background: Since 1994 at the authors' institution, approximately 9000 cardiac surgical procedures were performed using activated clotting time (ACT)-monitored heparin anticoagulation for cardiopulmonary bypass and protamine administration calculated from a standard unchanged formula. This formula incorporates physiologic consequences of bypass pump-induced dilutional coagulopathy, platelet dysfunction, and coagulation/fibrinolytic cascade component activation, and thus may overcorrect in a subset of off-pump coronary artery bypass graft (OPCAB) patients who may in fact manifest a relative perioperative hypercoagulability state. This study evaluated a strategy of decreased protamine dosing in OPCAB. Methods: Eighty consecutive OPCAB patients who underwent surgery performed by a single surgeon at a single institution over a 12-month period were retrospectively analyzed. Patients underwent a mean of 2.91 +/- 0.1 OPCAB grafts with full heparinization and 50% of the calculated protamine dose was administered. ACT, partial thromboplastin times, thoracostomy tube outputs, transfusions, and clinical outcomes were assessed. Results: Of 80 patients, 76 (95%) returned to baseline ACT values with 50% protamine dosing. All patients demonstrated intraoperative clinical evidence of hemostasis. Mean 8- and 24-hour thoracostomy tube outputs were 424 +/- 24 mL and 806 +/- 38 mL, respectively. A mean of 1.7 +/- 0.2 packed red blood cell transfusions/patient was administered. There were no transfusions of platelets, fresh frozen plasma, or cryoprecipitate; no reexplorations; and no mortalities. Patients were discharged a mean of 4.4 +/- 0.1 days postoperatively. Conclusion: A standard protamine dosing formula adequate for on-pump cardiac surgical procedures significantly overestimates protamine requirements for OPCAB. Patients treated with decreased protamine do not appear to have adverse outcomes.
View details for PubMedID 14980850
Repair of acute type A aortic dissection associated with temporal arteritis
ANNALS OF THORACIC SURGERY
2003; 76 (5): 1717-1718
The most common predisposing factor for aortic dissection is hypertension. Dissection is also seen in primary aortic diseases, including those that involve aortic inflammation. We report a case of successful repair of an acute type A aortic dissection in a patient with a history of temporal arteritis and pathologic evidence of giant cell aortitis. The literature concerning the association of aortic dissection and temporal arteritis is reviewed.
View details for DOI 10.1016/S0003-4975(03)00695-7
View details for Web of Science ID 000186358600081
View details for PubMedID 14602321
Gene transfer of hepatocyte growth factor attenuates postinfarction heart failure.
2003; 108: II230-6
Despite advances in surgical and percutaneous coronary revascularization, ongoing ischemia that is not amenable to standard revascularization techniques is a major cause of morbidity and mortality. Hepatocyte Growth Factor (HGF) has potent angiogenic and anti-apoptotic activities, and this study evaluated the functional and biochemical effects of HGF gene transfer in a rat model of postinfarction heart failure.Lewis rats underwent ligation of the left anterior descending coronary artery with direct intramyocardial injection of replication-deficient recombinant adenovirus encoding HGF (n=10) or empty null virus as control (n=9), and animals were analyzed after six weeks. Pressure-volume conductance catheter measurements demonstrated significantly preserved contractile function in the HGF group compared with Null control animals as measured by maximum developed LV pressure (79+/-5 versus 56+/-4 mm Hg, P<0.001) and maximum dP/dt (2890+/-326 versus 1622+/-159 mm Hg/sec, P<0.01). Significant preservation of LV geometry was associated with HGF treatment (LV Diameter HGF 13.1+/-0.54 versus Null 14.4+/-0.15 mm P<0.01; LV wall thickness 1.73+/-0.10 versus 1.28+/-0.07 mm P<0.01). Angiogenesis was significantly enhanced in HGF treated animals as measured by both Von Willebrand's Factor immunohistochemical staining and a microsphere assay. TUNEL analysis revealed a significant reduction in apoptosis in the HGF group (3.42+/-0.83% versus 8.36+/-1.16%, P<0.01), which correlated with increased Bcl-2 and Bcl-xL expression in the HGF animals.Hepatocyte Growth Factor gene transfer following a large myocardial infarction results in significantly preserved myocardial function and geometry, and is associated with significant angiogenesis and a reduction in apoptosis. This therapy may be useful as an adjunct or alternative to standard revascularization techniques in patients with ischemic heart failure.
View details for PubMedID 12970238
Blocking the development of postischemic cardiomyopathy with viral gene transfer of the apoptosis repressor with caspase recruitment domain
82nd Annual Meeting of the American-Association-for-Thoracic-Surgery
MOSBY-ELSEVIER. 2003: 1461–69
Apoptosis caused by acute ischemia and subsequent ventricular remodeling is implicated as a mediator of heart failure. This study was designed to assess the efficacy of in vivo viral gene transfer of the antiapoptotic factor apoptosis repressor with caspase recruitment domain to block apoptosis and preserve ventricular geometry and function.In a rabbit model of regional ischemia followed by reperfusion, an experimental group treated with adenovirus-apoptosis repressor with caspase recruitment domain was compared with empty vector adenovirus-null controls. Cardiac function was assessed by echocardiography and sonomicrometry of the border zone compared with the normal left ventricle. Animals were killed at 6 weeks with measurements of ventricular geometry and apoptosis.Animals with the apoptosis repressor with caspase recruitment domain (ARC group) maintained higher ejection fractions at 4 and 6 weeks, and sonomicrometry demonstrated greater protection of border zone fractional shortening at 6 weeks compared with the control group. The ARC group maintained superior preservation of left ventricular geometry with less ventricular dilation and wall thinning. Finally, there was reduced apoptosis in the rabbits treated with apoptosis repressor with caspase recruitment domain compared with the controls.Gene transfer of apoptosis repressor with caspase recruitment domain preserves left ventricular function after ischemia. The benefit at 6 weeks is postulated to result from an apoptosis repressor with caspase recruitment domain-mediated reduction in apoptosis and ventricular remodeling. Adenovirus-apoptosis repressor with caspase recruitment domain administration offers a potential strategy after myocardial ischemia to protect the heart from late postischemic cardiomyopathy.
View details for DOI 10.1016/S0022-5223(02)73229-7
View details for Web of Science ID 000183864700036
View details for PubMedID 12830068
Off-pump coronary artery bypass grafting attenuates postoperative bleeding associated with preoperative clopidogrel administration
9th Annual CTT Meeting
FORUM MULTIMEDIA PUBLISHING, LLC. 2003: 282–85
Clopidogrel is being increasingly administered as primary therapy for acute coronary syndromes and prior to planned percutaneous coronary intervention (PCI). In these settings, surgical revascularization results in signifi- cantly increased postoperative bleeding, transfusion, and reexploration. Off-pump coronary artery bypass grafting (OPCAB) may decrease the extent of postoperative bleeding in patients exposed to clopidogrel.The cases of 78 consecutive patients undergoing OPCAB by a single surgeon were retrospectively analyzed, and the patients were divided into 2 groups, those with immediately preoperative clopidogrel exposure (clopidogrel OPCAB, n = 15) and those without (control OPCAB, n = 63). Multiple perioperative parameters were statistically compared. The clopidogrel OPCAB group also was compared with a group of previously described on-pump coronary bypass patients who made up a historical control group (n = 59).Postoperative bleeding, transfusion requirements, reexploration rates, duration of mechanical ventilation, and length of stay were markedly less for clopidogrel OPCAB patients than for historical controls and were statistically equivalent to those of control OPCAB patients.Among these 15 OPCAB patients with immediately preoperative administration of clopidogrel and aspirin, outcome was improved compared with published results for on-pump coronary bypass patients and was equivalent to results among OPCAB patients not exposed to clopidogrel. Published, recommended approaches to clopidogrel administration, such as avoidance of pre-PCI clopidogrel, delay of surgery, and platelet transfusion do not appear to be necessary with OPCAB.
View details for Web of Science ID 000185916500002
View details for PubMedID 14721793
Minimally invasive video-assisted graft replacement of a descending thoracic aortic aneurysm
5th Annual Meeting of the International-Society-for-Minimally-Invasive-Cardiac-Surgery
FORUM MULTIMEDIA PUBLISHING, LLC. 2003: E59–E61
Standard surgical therapy of descending thoracic aortic aneurysms entails obligate extensive operative exposure that is associated with significant postoperative pain and morbidity. A 70-year-old patient with multiple significant comorbidities including severe chronic obstructive pulmonary disease (force expiratory volume at 1 second, 0.66 L) presented with a highly symptomatic, eccentric, descending thoracic aortic aneurysm. The patient underwent successful minimally invasive video-assisted graft repair of this aneurysm. This report represents the first known clinical application of this operative approach.
View details for Web of Science ID 000183699400033
View details for PubMedID 12821441
Advances in the treatment of acute type A dissection: An integrated approach
Aortic Surgery Symposium VIII
ELSEVIER SCIENCE INC. 2002: S1848–S1852
Acute type A dissections require surgery to prevent death from proximal aortic rupture or malperfusion. Most series over the past decade have reported a death rate in the range of 15% to 30%. The objective of this study is to examine the effect of an integrated surgical approach on the treatment of acute type A dissections.From January 1994 to April 2002, 163 consecutive patients underwent repair of acute type A dissection. All had an integrated operative management as follows: intraoperative transesophageal echocardiography; hypothermic circulatory arrest (HCA) with retrograde cerebral perfusion to replace the aortic arch; HCA established after 3 minutes of electroencephalographic silence in neuromonitored patients (60%) or after 45 minutes of cooling in patients who were not neuromonitored (40%); reinforcement of the residual arch tissue with a Teflon felt "neo-media;" cannulation of the arch graft to reestablish cardiopulmonary bypass at the completion of HCA (antegrade graft perfusion); and remodeling of the sinus of Valsalva segments with Teflon felt "neo-media" and aortic valve resuspension or replacement with a biological or mechanical valved conduit. When HCA times were greater than 50 minutes, antegrade cerebral perfusion is used. Since Februay 1999, BioGlue has been used as an anastomotic adjunct in the repair of type A dissections.Mean age was 62 +/- 14 years, with 68% men and 15% with previous cardiac surgery. Seven percent of patients presented with a preoperative neurologic deficit, and 3% developed a new cerebrovascular accident after dissection repair. The in-hospital death rate was 9.8%. Excluding the patients with preoperative strokes (7%) and those with postoperative stroke (3%), the in-hospital death rate was 6.6%. In 6 patients, prompt changes in circulatory management consisting of switching cannulation sites or cross-clamp release with direct temporary aortic arch fenestration occurred when there were sudden changes in electroencephalogram during cooling.A standardized approach to the treatment of acute type A dissections has improved outcomes. Our 55% mortality in patients with preoperative cerebral vascular accident (CVA) suggests that this group may be candidates for medical or delayed surgical treatment. Conversely, our 6.6% mortality rate for neurologically intact patients warrants aggressive and expeditious surgical intervention.
View details for Web of Science ID 000179262300109
View details for PubMedID 12440679
Viral gene transfer of the antiapoptotic factor Bcl-2 protects against chronic postischemic heart failure.
2002; 106 (12): I212-7
Apoptosis secondary to acute ischemia and chronic remodeling is implicated as a mediator of heart failure. This study was designed to assess the effect of in vivo viral gene transfer of the anti-apoptotic factor Bcl-2 to block apoptosis and preserve ventricular geometry and function.In a rabbit model of regional ischemia followed by reperfusion, an experimental group treated with adeno-Bcl-2 was compared with a control group receiving empty vector adeno-null. Function was assessed by echocardiography, and sonomicrometry of the border zone was compared with the normal left ventricle (LV). Animals were killed at 6 weeks, and an additional group was killed after 3 days to see whether virus administration conferred an immediate effect. Animals that were administered Bcl-2 maintained higher ejection fractions at 2, 4, and 6 weeks compared with controls. Sonomicrocrystals demonstrated greater protection of border zone fractional shortening at 6 weeks. The Bcl-2 group had superior preservation of LV geometry with less ventricular dilatation and wall thinning. There was also reduced apoptosis compared with the controls. Finally, in the animals killed at 3 days, no functional difference was observed between the Bcl-2 and control groups.Gene transfer of Bcl-2 preserves LV function after ischemia despite the absence of an observed acute protective effect. The benefit at 6 weeks is postulated to result from a Bcl-2-mediated reduction in apoptosis and ventricular remodeling. Adeno-Bcl-2 administration offers a potential strategy to protect the heart from late postischemic heart failure.
View details for PubMedID 12354736
Efficient transmural cardiac gene transfer by intrapericardial injection in neonatal mice
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
1999; 31 (4): 721-732
An efficient cardiac gene transfer technique in murine models would greatly facilitate the elucidation of the pathophysiology of cardiomyopathies and the development of genetic therapies. Direct myocardial injection or catheter-based intracoronary infusion is not easily achievable in mice and resultant transgene expression is often limited in distribution. A replication-defective, recombinant adenovirus encoding luciferase (5x10(9)pfu) or lacZ (4-5x10(10)particles/animal) was injected percutaneously into the pericardial cavity of 4-5 day old mice. Chemiluminescence assay for luciferase activity at 3 days post-injection revealed the highest activity in the heart (heart=288+/-110, lungs=19+/-5, liver=11+/-5 ng/gm tissue, n=11). X-gal staining of cryostat sections demonstrated widespread transmural lacZ expression in the left ventricle, interventricular septum, right ventricle, and atrial appendages, and the average fractional area of X-gal staining in a left ventricle was 66+/-16% (range 40-92%, n=21 sections). However, the long-term survival of these mice was compromised. Reduction in the injectate volume by 50% significantly improved survival but concurrently reduced lacZ expression. Significant lacZ expression was observed in the right ventricle and interventricular septum but left ventricular expression was predominantly epicardial, with variable myocardial penetration. At 2 months post-injection, lacZ expression persisted only in atrial tissues, pulmonary veins, and great vessels. Despite lack of persistent transgene expression in ventricular tissues, the high degree of transgene expression achieved may be sufficient to allow evaluation of short-term effects of specific genetic manipulations in the heart.
View details for Web of Science ID 000079914600003
View details for PubMedID 10329200
Recombinant adenovirus-mediated cardiac gene transfer of superoxide dismutase and catalase attenuates postischemic contractile dysfunction
1998; 98 (19): II255-II260
Coronary revascularization entails obligatory myocardial ischemia followed by reperfusion with occasional resultant postischemic contractile dysfunction, a state associated with significant morbidity and mortality. This injury is attributed in part to oxygen free radicals and has been partially ameliorated with exogenous antioxidants, a strategy limited by agent instability, low titer, and inadequate cardiomyocyte uptake. Cardiac gene transfer with antioxidant encoding vectors may significantly enhance intracellular free radical scavenger activity.C57/BL6 neonatal mice (age, 2 days; n = 131) underwent intrapericardial delivery of recombinant adenoviruses encoding superoxide dismutase (SOD) and catalase (Cat) (n = 76) or beta-galactosidase (LacZ) as a control (n = 55). After 3 days, hearts were explanted, and SOD and Cat transgene expression was detected by Western blot analysis. Spectrophotometric enzyme assays demonstrated enhanced SOD activity 1.6-fold (P < 0.0001) and Cat 3.6-fold (P < 0.00001) in experimental versus LacZ hearts. Isolated perfused hearts were subjected to 5 minutes of warm ischemia, and at 5, 10, and 15 minutes after initiation of reperfusion, LacZ controls lost 24%, 33%, and 41% of peak systolic apicobasal force, respectively, whereas experimental hearts lost 5%, 12%, and 20% (P < 0.001, each time point). In controls, rate of force generation diminished 8%, 17%, and 35%; in experimental hearts, it increased 1% at 5 minutes and decreased 5% and 15% and 10 and 15 minutes (P < 0.01, P < 0.05, P < 0.05). LacZ hearts exhibited dysfunction similar to hearts from uninjected animals (P = NS, each time point).Adenovirus-mediated cardiac gene transfer and expression of SOD and Cat augment antioxidant enzyme activity and minimize contractile dysfunction after ischemic reperfusion in the isolated perfused neonatal mouse heart.
View details for Web of Science ID 000076886100067
View details for PubMedID 9852911
In utero cardiac gene transfer via intraplacental delivery of recombinant adenovirus
1997; 96 (10): 3561-3569
The relationship among the maternal, placental, and uniquely shunted embryonic circulation was explored to provide access to the embryonic cardiovascular system in utero. Manipulation of gene expression in the developing heart would be particularly useful for studying the effects of altered gene expression on cardiac development and in the etiology of congenital cardiac anomalies.Dye studies demonstrated that intraplacental injection allows direct access to the embryonic cardiac and systemic circulation. To evaluate the efficacy of cardiac gene transfer using this approach, replication-deficient recombinant adenoviral vectors encoding luciferase or beta-galactosidase as reporter genes were injected intraplacentally into embryonic day (E)12.5 murine embryos, an age at which the mass of the heart was observed to be large compared with other organs. Embryos were assayed for transgene expression at E15.5 and at birth. Survival rates at these times were similar among vector-injected and control groups. At E15.5 and at birth, luciferase activity within the heart was 9- and 23-fold higher, respectively, than in the remainder of the embryo, although levels of expression were generally lower at birth than during embryonic life. Beta-galactosidase expression was observed within all regions of the embryonic heart and was localized to approximately 15% of atrial and ventricular cells.Intraplacental delivery of adenovirus at embryonic day 12.5 results in somatic gene transfer to the murine embryonic heart, which persists at least until birth. The combination of intraplacental injection to directly access the fetal coronary circulation and injection at E12.5 when the mass of the heart is large compared with other organs results in transgene expression in cardiac cells. Intraplacental injections early in embryonic life may thus be useful to study the effects of temporal manipulation of gene expression on cardiac development and disease.
View details for Web of Science ID A1997YH18800049
View details for PubMedID 9396456
Circulatory management with retrograde cerebral perfusion for acute type A aortic dissection.
1996; 94 (9): II173-6
Cerebral circulation during urgent repair of acute type A aortic dissection has traditionally been managed with cardiopulmonary bypass and aortic cross clamping proximal to the innominate artery or by the use of hypothermic circulatory arrest (HCA). The more recently introduced retrograde cerebral perfusion (RCP) may confer additional cerebral protection during elective aortic arch reconstruction. The purpose of this study was to demonstrate the efficacy of RCP in the urgent repair of acute type A aortic dissection.We evaluated 60 consecutive patients who underwent repair of acute type A aortic dissection over a 6-year period. Patients were grouped according to intraoperative circulatory management strategies. Group 1 consisted of 41 patients operated on early in the series who were managed by cardiopulmonary bypass and standard aortic cross clamping (n = 21) with conversion to HCA (n = 20) if the intimal tear extended into the aortic arch. Since 1993, 19 patients, who make up group 2, were managed with routine open distal anastomosis and HCA with RCP. Data were analyzed for clinically evident, radiographically confirmed cerebrovascular accidents and 60-day mortality and evaluated by chi 2 analysis. Stroke and mortality rates of patients managed with either cardiopulmonary bypass or HCA were 26.3% and 29.3%, respectively. Patients undergoing RCP experienced statistically significant reductions in rates of confirmed cerebrovascular accidents (0%, P = .015) and mortality (5.3%, P = .04).We conclude that the introduction of circulatory management using RCP with HCA during urgent operative repair of acute type A aortic dissection has significantly improved both stroke and mortality rates.
View details for PubMedID 8901741
- Retrograde cerebral and distal aortic perfusion during ascending and thoracoabdominal aortic surgery Annals Thoracic Surg 1995; 60: 345-353