Adjunct Professor, Medicine - Cardiovascular Medicine
Adjunct Professor, Bioengineering (2014 - Present)
Executive Education Program Co-Director, Stanford Biodesign (2013 - Present)
Innovation Fellowship Program Director, Stanford Biodesign (2007 - Present)
Innovation Course Co-Director, Stanford Biodesign (2006 - Present)
Chio, S.S., Brinton, T.J.. "United States Patent RE38,159 A Non-invasive Method and Apparatus for Diagnosing and Monitoring Aortic Valve Abnormalities, Such as Aortic Regurgitation", Pulse Metric, Inc., Jun 24, 2003
FAME II - Fractional Flow Reserve (FFR) Guided Percutaneous Coronary Intervention (PCI) Plus Optimal Medical Treatment (OMT) Verses OMT
The overall purpose of the FAME II trial is to compare the clinical outcomes, safety and cost-effectiveness of FFR-guided PCI plus optimal medical treatment (OMT) versus OMT alone in patients with stable coronary artery disease.
Stanford is currently not accepting patients for this trial. For more information, please contact Maria Perlas, (650) 723 - 2094.
TAXUS Libertē Post Approval Study
The TAXUS Libertē Post-Approval Study is an FDA-mandated prospective, multi-center study designed to collect real-world safety and clinical outcomes in approximately 4,200 patients receiving one or more TAXUS Liberté Paclitaxel-Eluting Stents and prasugrel as part of a dual antiplatelet therapy (DAPT) drug regimen. This study will also contribute patient data to an FDA-requested and industry-sponsored research study that will evaluate the optimal duration of dual antiplatelet therapy (DAPT Study).
Stanford is currently not accepting patients for this trial. For more information, please contact Yvonne Strawa, (650) 498 - 7028.
- Independent Studies (5)
Prior Year Courses
- Biodesign Innovation: Concept Development and Implementation
BIOE 374B, ME 368B, MED 272B (Spr)
- Biodesign Innovation: Concept Development and Implementation
OIT 385 (Spr)
- Biodesign Innovation: Needs Finding and Concept Creation
BIOE 374A, ME 368A, MED 272A (Win)
- Biodesign Innovation: Concept Development and Implementation
- Intravascular lithotripsy to treat a severely underexpanded coronary stent EUROINTERVENTION 2019; 15 (1): 124–25
Feasibility of Shockwave Coronary Intravascular Lithotripsy for the Treatment of Calcified Coronary Stenoses.
2019; 139 (6): 834–36
View details for PubMedID 30715944
- Safety and Performance of Lithoplasty for Treatment of Calcified Peripheral Artery Lesions JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2017; 70 (7): 908–10
Needs-Based Innovation in Interventional Radiology: The Biodesign Process
TECHNIQUES IN VASCULAR AND INTERVENTIONAL RADIOLOGY
2017; 20 (2): 84–89
There are many possible mechanisms for innovation and bringing new technology into the marketplace. The Stanford Biodesign innovation process is based in a deep understanding of clinical unmet needs as the basis for focused ideation and development. By identifying and vetting a compelling unmet need, the aspiring innovator can "derisk" a project and maximize chances for successful development in an increasingly challenging regulatory and economic environment. As a specialty founded by tinkerers, with a history of disruptive innovation that has yielded countless new ways of delivering care with minimal invasiveness, lower morbidity, and lower cost, interventional radiologists are uniquely well positioned to identify unmet needs and develop novel solutions free of dogmatic convention.
View details for PubMedID 28673651
- The Impact of Postgraduate Health Technology Innovation Training: Outcomes of the Stanford Biodesign Fellowship ANNALS OF BIOMEDICAL ENGINEERING 2017; 45 (5): 1163-1171
PERFORMANCE OF THE LITHOPLASTY SYSTEM IN TREATING CALCIFIED CORONARY LESIONS PRIOR TO STENTING: RESULTS FROM THE DISRUPT CAD OCT SUB-STUDY
ELSEVIER SCIENCE INC. 2017: 1121
View details for Web of Science ID 000397342301643
Optical Coherence Tomography Characterization of Coronary Lithoplasty for Treatment of Calcified Lesions: First Description.
JACC. Cardiovascular imaging
2017; 10 (8): 897–906
This study sought to determine the mechanistic effects of a novel balloon-based lithoplasty system on heavily calcified coronary lesions and subsequent stent placement using optical coherence tomography (OCT).The Shockwave Coronary Rx Lithoplasty System (Shockwave Medical, Fremont, California) delivers localized, lithotripsy-enhanced disruption of calcium within the target lesion (i.e., lithoplasty) for vessel preparation before stent implantation.We analyzed OCT findings in 31 patients in whom lithoplasty was used to treat severely calcified stenotic coronary lesions.After lithoplasty, intraplaque calcium fracture was identified in 43% of lesions, with circumferential multiple fractures noted in >25%. The frequency of calcium fractures per lesion increased in the most severely calcified plaques (highest tertile vs. lowest tertile; p = 0.009), with a trend toward greater incidence of calcium fracture (77.8% vs. 22.2%; p = 0.057). Post-lithoplasty, mean acute area gain was 2.1 mm2, which further increased with stent implantation, achieving a minimal stent area of 5.94 ± 1.98 mm2 and mean stent expansion of 112.0 ± 37.2%. Deep dissections, as part of the angioplasty effect, occurred in 13% of cases and were successfully treated with stent implantation without incidence of acute closure, slow flow/no reflow, or perforation.High-resolution imaging by OCT delineated calcium modification with fracture as a major mechanism of action of lithoplasty in vivo and demonstrated efficacy in the achievement of significant acute area gain and favorable stent expansion.
View details for PubMedID 28797412
The Impact of Postgraduate Health Technology Innovation Training: Outcomes of the Stanford Biodesign Fellowship.
Annals of biomedical engineering
Stanford Biodesign launched its Innovation Fellowship in 2001 as a first-of-its kind postgraduate training experience for teaching biomedical technology innovators a need-driven process for developing medical technologies and delivering them to patients. Since then, many design-oriented educational programs have been initiated, yet the impact of this type of training remains poorly understood. This study measures the career focus, leadership trajectory, and productivity of 114 Biodesign Innovation Fellowship alumni based on survey data and public career information. It also compares alumni on certain publicly available metrics to finalists interviewed but not selected. Overall, 60% of alumni are employed in health technology in contrast to 35% of finalists interviewed but not selected. On leadership, 72% of alumni hold managerial or higher positions compared to 48% of the finalist group. A total of 67% of alumni reported that the fellowship had been "extremely beneficial" on their careers. As a measure of technology translation, more than 440,000 patients have been reached with technologies developed directly out of the Biodesign Innovation Fellowship, with another 1,000,000+ aided by solutions initiated by alumni after their training. This study suggests a positive impact of the fellowship program on the career focus, leadership, and productivity of its alumni.
View details for DOI 10.1007/s10439-016-1777-1
View details for PubMedID 28004213
View details for PubMedCentralID PMC5397448
Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part II. In Vivo Imaging of Bone Marrow Stromal Cells in Swine with PET/CT and MR Imaging.
2016; 280 (3): 826-836
Purpose To quantitatively determine the limit of detection of marrow stromal cells (MSC) after cardiac cell therapy (CCT) in swine by using clinical positron emission tomography (PET) reporter gene imaging and magnetic resonance (MR) imaging with cell prelabeling. Materials and Methods Animal studies were approved by the institutional administrative panel on laboratory animal care. Seven swine received 23 intracardiac cell injections that contained control MSC and cell mixtures of MSC expressing a multimodality triple fusion (TF) reporter gene (MSC-TF) and bearing superparamagnetic iron oxide nanoparticles (NP) (MSC-TF-NP) or NP alone. Clinical MR imaging and PET reporter gene molecular imaging were performed after intravenous injection of the radiotracer fluorine 18-radiolabeled 9-[4-fluoro-3-(hydroxyl methyl) butyl] guanine ((18)F-FHBG). Linear regression analysis of both MR imaging and PET data and nonlinear regression analysis of PET data were performed, accounting for multiple injections per animal. Results MR imaging showed a positive correlation between MSC-TF-NP cell number and dephasing (dark) signal (R(2) = 0.72, P = .0001) and a lower detection limit of at least approximately 1.5 × 10(7) cells. PET reporter gene imaging demonstrated a significant positive correlation between MSC-TF and target-to-background ratio with the linear model (R(2) = 0.88, P = .0001, root mean square error = 0.523) and the nonlinear model (R(2) = 0.99, P = .0001, root mean square error = 0.273) and a lower detection limit of 2.5 × 10(8) cells. Conclusion The authors quantitatively determined the limit of detection of MSC after CCT in swine by using clinical PET reporter gene imaging and clinical MR imaging with cell prelabeling. (©) RSNA, 2016 Online supplemental material is available for this article.
View details for DOI 10.1148/radiol.2016151150
View details for PubMedID 27332865
Multimodality Molecular Imaging of Cardiac Cell Transplantation: Part I. Reporter Gene Design, Characterization, and Optical in Vivo Imaging of Bone Marrow Stromal Cells after Myocardial Infarction.
2016; 280 (3): 815-825
Purpose To use multimodality reporter-gene imaging to assess the serial survival of marrow stromal cells (MSC) after therapy for myocardial infarction (MI) and to determine if the requisite preclinical imaging end point was met prior to a follow-up large-animal MSC imaging study. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care. Mice (n = 19) that had experienced MI were injected with bone marrow-derived MSC that expressed a multimodality triple fusion (TF) reporter gene. The TF reporter gene (fluc2-egfp-sr39ttk) consisted of a human promoter, ubiquitin, driving firefly luciferase 2 (fluc2), enhanced green fluorescent protein (egfp), and the sr39tk positron emission tomography reporter gene. Serial bioluminescence imaging of MSC-TF and ex vivo luciferase assays were performed. Correlations were analyzed with the Pearson product-moment correlation, and serial imaging results were analyzed with a mixed-effects regression model. Results Analysis of the MSC-TF after cardiac cell therapy showed significantly lower signal on days 8 and 14 than on day 2 (P = .011 and P = .001, respectively). MSC-TF with MI demonstrated significantly higher signal than MSC-TF without MI at days 4, 8, and 14 (P = .016). Ex vivo luciferase activity assay confirmed the presence of MSC-TF on days 8 and 14 after MI. Conclusion Multimodality reporter-gene imaging was successfully used to assess serial MSC survival after therapy for MI, and it was determined that the requisite preclinical imaging end point, 14 days of MSC survival, was met prior to a follow-up large-animal MSC study. (©) RSNA, 2016 Online supplemental material is available for this article.
View details for DOI 10.1148/radiol.2016140049
View details for PubMedID 27308957
Externally Delivered Focused Ultrasound for Renal Denervation
2016; 9 (12): 1292-1299
The aim of this study was to assess clinical safety and efficacy outcomes of renal denervation executed by an externally delivered, completely noninvasive focused therapeutic ultrasound device.Renal denervation has emerged as a potential treatment approach for resistant hypertension.Sixty-nine subjects received renal denervation with externally delivered focused ultrasound via the Kona Medical Surround Sound System. This approach was investigated across 3 consecutive studies to optimize targeting, tracking, and dosing. In the third study, treatments were performed in a completely noninvasive way using duplex ultrasound image guidance to target the therapy. Short- and long-term safety and efficacy were evaluated through use of clinical assessments, magnetic resonance imaging scans prior to and 3 and 24 weeks after renal denervation, and, in cases in which a targeting catheter was used to facilitate targeting, fluoroscopic angiography with contrast.All patients tolerated renal denervation using externally delivered focused ultrasound. Office blood pressure (BP) decreased by 24.6 ± 27.6/9.0 ± 15.0 mm Hg (from baseline BP of 180.0 ± 18.5/97.7 ± 13.7 mm Hg) in 69 patients after 6 months and 23.8 ± 24.1/10.3 ± 13.1 mm Hg in 64 patients with complete 1-year follow-up. The response rate (BP decrease >10 mm Hg) was 75% after 6 months and 77% after 1 year. The most common adverse event was post-treatment back pain, which was reported in 32 of 69 patients and resolved within 72 h in most cases. No intervention-related adverse events involving motor or sensory deficits were reported. Renal function was not altered, and vascular safety was established by magnetic resonance imaging (all patients), fluoroscopic angiography (n = 48), and optical coherence tomography (n = 5).Using externally delivered focused ultrasound and noninvasive duplex ultrasound, image-guided targeting was associated with substantial BP reduction without any major safety signals. Further randomized, sham-controlled trials will be needed to validate this unique approach.
View details for DOI 10.1016/j.jcin.2016.04.013
View details for Web of Science ID 000378169500018
View details for PubMedID 27339848
The impact of postgraduate health technology innovation training: Outcomes of the Stanford Biodesign Fellowship.
Annals of Biomedical Engineering
View details for DOI 10.1007/s10439-016-1777-1
Needs-Based Innovation in Cardiovascular Medicine: The Stanford Biodesign Process.
JACC. Basic to translational science
2016; 1 (6): 541–47
More than a decade ago, a formalized fellowship training program in medical device innovation, the first of its kind, was created at Stanford University. Now in its 15th year, the Stanford Biodesign Fellowship Program is a 10-month program whereby postgraduate students with a prior background in medicine, engineering, and/or business form interdisciplinary teams for an experiential process of identifying unmet clinical needs, inventing new solutions, and implementing these ideas (the 3 "I's"). A key component of this structured process is focused attention on needs finding and characterization, which differs from the traditional "tech-push" model (i.e., technologies looking for problems to solve). Although the Stanford Biodesign process can be applied to a wide variety of clinical areas, cardiovascular medicine is particularly well suited, given the breadth of clinical presentations it touches and its history of innovation to solve important clinical problems. Physicians play a vital role in the process, especially for needs identification and characterization. This paper outlines the Stanford Biodesign process and presents an argument for its repeat applicability, discusses its relevance to physicians and to cardiologists in particular, and provides a case study of the process that resulted in a currently available cardiovascular medical technology that came directly from the Fellowship Program.
View details for PubMedID 30167537
Needs-Based Innovation in Cardiovascular Medicine The Stanford Biodesign Process
JACC. Basic to translational science
2016; 1 (6): 541-547
View details for DOI 10.1016/j.jacbts.2016.06.011
- Non-invasive Renal Denervation Using Externally Delivered Focused Ultrasound: Early Experience Using Doppler based Imaging Tracking and Targeting for Treatment ELSEVIER SCIENCE INC. 2014: B121
Intracoronary and Retrograde Coronary Venous Myocardial Delivery of Adipose-Derived Stem Cells in Swine Infarction Lead to Transient Myocardial Trapping with Predominant Pulmonary Redistribution
CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS
2014; 83 (1): E17-E25
To examine the comparative fate of adipose-derived stem cells (ASCs) as well as their impact on coronary microcirculation following either retrograde coronary venous (RCV) or arterial delivery.Local delivery of ASCs to the heart has been proposed as a practical approach to limiting the extent of myocardial infarction. Mouse models of mesenchymal stem cell effects on the heart have also demonstrated significant benefits from systemic (intravenous) delivery, prompting a question about the advantage of local delivery. There has been no study addressing the extent of myocardial vs. systemic disposition of ASCs in large animal models following local delivery to the myocardium.In an initial experiment, dose-dependent effects of ASC delivery on coronary circulation in normal swine were evaluated to establish a tolerable ASC dosing range for intracoronary (IC) delivery. In a set of subsequent experiments, an anterior acute myocardial infarction (AMI) was created by balloon occlusion of the proximal left anterior descending (LAD) artery, followed by either IC or RCV infusion of 10(7) (111)Indium-labeled autologous ASCs 6 days following AMI. Indices of microcirculatory resistance (IMR) and coronary flow reserve (CFR) were measured before sacrifices to collect tissues for analysis at 1 or 24 hr after cell delivery.IC delivery of porcine ASCs to normal myocardium was well tolerated up to a cumulative dose of 14 × 10(6) cells (approximately 0.5 × 10(6) cells/kg). There was evidence suggesting microcirculatory trapping of ASC: at unit doses of 50 × 10(6) ASCs, IMR and CFR were found to be persistently altered in the target LAD distribution at 7 days following delivery, whereas at 10 × 10(6) ASCs, only CFR was altered. In the context of recent MI, a significantly higher percentage of ASCs was retained at 1 hr with IC delivery compared with RCV delivery (57.2 ± 12.7% vs. 17.9 ± 1.6%, P = 0.037) but this initial difference was not apparent at 24 hr (22.6 ± 5.5% vs. 18.7 ± 8.6%; P = 0.722). In both approaches, most ASC redistributed to the pulmonary circulation by 24 hr postdelivery. There were no significant differences in CFR or IMR following ASC delivery to infarcted tissue by either route.Selective intravascular delivery of ASC by coronary arterial and venous routes leads to similarly limited myocardial cell retention with predominant redistribution of cells to the lungs. IC arterial delivery of ASC leads to only transiently greater myocardial retention, which is accompanied by obstruction of normal regions of coronary microcirculation at higher doses. The predominant intrapulmonary localization of cells following local delivery via both methods prompts the notion that systemic delivery of ASC might provide similarly beneficial outcomes while avoiding risks of inadvertent microcirculatory compromise.
View details for DOI 10.1002/ccd.24659
View details for Web of Science ID 000328631400006
View details for PubMedID 22972685
Outcomes from a Postgraduate Biomedical Technology Innovation Training Program: The First 12 Years of Stanford Biodesign
ANNALS OF BIOMEDICAL ENGINEERING
2013; 41 (9): 1803-1810
The Stanford Biodesign Program began in 2001 with a mission of helping to train leaders in biomedical technology innovation. A key feature of the program is a full-time postgraduate fellowship where multidisciplinary teams undergo a process of sourcing clinical needs, inventing solutions and planning for implementation of a business strategy. The program places a priority on needs identification, a formal process of selecting, researching and characterizing needs before beginning the process of inventing. Fellows and students from the program have gone on to careers that emphasize technology innovation across industry and academia. Biodesign trainees have started 26 companies within the program that have raised over $200 million and led to the creation of over 500 new jobs. More importantly, although most of these technologies are still at a very early stage, several projects have received regulatory approval and so far more than 150,000 patients have been treated by technologies invented by our trainees. This paper reviews the initial outcomes of the program and discusses lessons learned and future directions in terms of training priorities.
View details for DOI 10.1007/s10439-013-0761-2
View details for Web of Science ID 000323736800002
View details for PubMedID 23404074
Cost-effectiveness landscape analysis of treatments addressing xerostomia in patients receiving head and neck radiation therapy.
Oral surgery, oral medicine, oral pathology and oral radiology
2013; 116 (1): e37-51
Head and neck (H&N) radiation therapy (RT) can induce irreversible damage to the salivary glands thereby causing long-term xerostomia or dry mouth in 68%-85% of the patients. Not only does xerostomia significantly impair patients' quality-of-life (QOL) but it also has important medical sequelae, incurring high medical and dental costs. In this article, we review various measures to assess xerostomia and evaluate current and emerging solutions to address this condition in H&N cancer patients. These solutions typically seek to accomplish 1 of the 4 objectives: (1) to protect the salivary glands during RT, (2) to stimulate the remaining gland function, (3) to treat the symptoms of xerostomia, or (4) to regenerate the salivary glands. For each treatment, we assess its mechanisms of action, efficacy, safety, clinical utilization, and cost. We conclude that intensity-modulated radiation therapy is both the most widely used prevention approach and the most cost-effective existing solution and we highlight novel and promising techniques on the cost-effectiveness landscape.
View details for DOI 10.1016/j.oooo.2013.02.017
View details for PubMedID 23643579
- Gastroenterology and Biodesign: Contributing to the Future of Our Specialty GASTROENTEROLOGY 2013; 144 (2): 258-262
Applying a Structured Innovation Process to Interventional Radiology: A Single-Center Experience
JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
2012; 23 (4): 488-494
To determine the feasibility and efficacy of applying an established innovation process to an active academic interventional radiology (IR) practice.The Stanford Biodesign Medical Technology Innovation Process was used as the innovation template. Over a 4-month period, seven IR faculty and four IR fellow physicians recorded observations. These observations were converted into need statements. One particular need relating to gastrostomy tubes was diligently screened and was the subject of a single formal brainstorming session.Investigators collected 82 observations, 34 by faculty and 48 by fellows. The categories that generated the most observations were enteral feeding (n = 9, 11%), biopsy (n = 8, 10%), chest tubes (n = 6, 7%), chemoembolization and radioembolization (n = 6, 7%), and biliary interventions (n = 5, 6%). The output from the screening on the gastrostomy tube need was a specification sheet that served as a guidance document for the subsequent brainstorming session. The brainstorming session produced 10 concepts under three separate categories.This formalized innovation process generated numerous observations and ultimately 10 concepts to potentially to solve a significant clinical need, suggesting that a structured process can help guide an IR practice interested in medical innovation.
View details for DOI 10.1016/j.jvir.2011.12.029
View details for Web of Science ID 000302396300009
View details for PubMedID 22464713
Dual Manganese-Enhanced and Delayed Gadolinium-Enhanced MRI Detects Myocardial Border Zone Injury in a Pig Ischemia-Reperfusion Model
2011; 4 (5): 574-582
Gadolinium (Gd)-based delayed-enhancement MRI (DEMRI) identifies nonviable myocardium but is nonspecific and may overestimate nonviable territory. Manganese (Mn(2+))-enhanced MRI (MEMRI) denotes specific Mn(2+) uptake into viable cardiomyocytes. We performed a dual-contrast myocardial assessment in a porcine ischemia-reperfusion (IR) model to test the hypothesis that combined DEMRI and MEMRI identifies viable infarct border zone (BZ) myocardium in vivo.Sixty-minute left anterior descending coronary artery IR injury was induced in 13 adult swine. Twenty-one days post-IR, 3-T cardiac MRI was performed. MEMRI was obtained after injection of 0.7 mL/kg Mn(2+) contrast agent. DEMRI was then acquired after injection of 0.2 mmol/kg Gd. Left ventricular (LV) mass, infarct, and function were analyzed. Subtraction of MEMRI defect from DEMRI signal identified injured BZ myocardium. Explanted hearts were analyzed by 2,3,5-triphenyltetrazolium chloride stain and tissue electron microscopy to compare infarct, BZ, and remote myocardium. Average LV ejection fraction was reduced (30±7%). MEMRI and DEMRI infarct volumes correlated with 2,3,5-triphenyltetrazolium chloride stain analysis (MEMRI, r=0.78; DEMRI, r=0.75; P<0.004). MEMRI infarct volume percentage was significantly lower than that of DEMRI (14±4% versus 23±4%; P<0.05). BZ MEMRI signal-to-noise ratio (SNR) was intermediate to remote and core infarct SNR (7.5±2.8 versus 13.2±3.4 and 2.9±1.6; P<0.0001), and DEMRI BZ SNR tended to be intermediate to remote and core infarct SNR (8.4±5.4 versus 3.3±0.6 and 14.3±6.6; P>0.05). Tissue electron microscopy analysis exhibited preserved cell structure in BZ cardiomyocytes despite transmural DEMRI enhancement.The dual-contrast MEMRI-DEMRI detects BZ viability within DEMRI infarct zones. This approach may identify injured, at-risk myocardium in ischemic cardiomyopathy.
View details for DOI 10.1161/CIRCIMAGING.110.960591
View details for PubMedID 21719779
Teaching Biomedical Technology Innovation as a Discipline
SCIENCE TRANSLATIONAL MEDICINE
2011; 3 (92)
Recently, universities in the United States and abroad have developed dedicated educational programs in life science technology innovation. Here, we discuss the two major streams of educational theory and practice that have informed these programs: design thinking and entrepreneurship education. We make the case that the process of innovation for new medical technologies (medtech) is different from that for biopharmaceuticals and outline the challenges and opportunities associated with developing a discipline of medtech innovation.
View details for DOI 10.1126/scitranslmed.3002222
View details for Web of Science ID 000292982600001
View details for PubMedID 21775665
RevaTen platelet-rich plasma improves cardiac function after myocardial injury.
Cardiovascular revascularization medicine : including molecular interventions
2011; 12 (3): 158-163
Cell therapy is an exciting area of investigation for repair of injured myocardial tissue. Platelet-rich plasma (PRP) is an autologous fractionation of whole blood containing high concentrations of growth factors including vascular endothelial growth factor and insulin-like growth factor, among many others. PRP has been shown to safely and effectively enhance healing of musculoskeletal tissue primarily by reparative cell signaling. Despite a growing body of evidence on PRP's safety and efficacy, limited studies have been performed using PRP in cardiovascular tissues. Utilizing a murine myocardial permanent ligation and ischemia/reperfusion model, this study sought to determine whether RevaTen PRP (Menlo Park, CA, USA), a proprietary formulation of PRP, improves cardiac function as measured by left ventricular ejection fraction (LVEF).Via thoracotomy, the left anterior descending arteries (LAD) of 28 mice were occluded by suture either permanently or for 45 min to induce ischemic injury and then reperfused. Mice undergoing permanent ligation had intramyocardial injections of either RevaTen PRP (n=5) or phosphate-buffered saline (PBS; n=4). Magnetic resonance (MR) imaging was performed to calculate LVEF at 7 days. Mice undergoing ischemia and reperfusion had intramyocardial injections of either PRP (n=10) or PBS (n=9) and underwent MR imaging to calculate LVEF at 21 days. Hearts were harvested for histologic examination following imaging.Compared with PBS controls, RevaTen PRP-treated animals that underwent LAD ligation had a 38% higher LVEF 7 days after injury (PRP=36.1±6.1%; PBS=26.4±3.6%, P=.027). Compared with PBS controls, PRP-treated animals who underwent ischemia-reperfusion of the LAD had a 28% higher LVEF 21 days after injury (PRP=37.6±4.8%, control=29.3±9.7%, P=.038). Histologic analysis suggested the presence of more scar tissue in the control group compared to the PRP-treated animals.MR imaging demonstrated a positive effect of RevaTen PRP on left ventricular function in both a ligation and ischemia-reperfusion murine model. Our results suggest RevaTen PRP should be investigated further as a potential point-of-care biologic treatment following myocardial injury.
View details for DOI 10.1016/j.carrev.2010.08.005
View details for PubMedID 21122486
Detection of Injured Border Zone Myocardium Using Manganese-Enhanced and Delayed-Enhanced MRI in a Pig Ischemia-Reperfusion Model
LIPPINCOTT WILLIAMS & WILKINS. 2010
View details for Web of Science ID 000208231600841
Imaging Gene Expression in Human Mesenchymal Stem Cells: From Small to Large Animals
2009; 252 (1): 117-127
To evaluate the feasibility of reporter gene imaging in implanted human mesenchymal stem cells (MSCs) in porcine myocardium by using clinical positron emission tomography (PET)-computed tomography (CT) scanning.Animal protocols were approved by the Institutional Administrative Panel on Laboratory Animal Care. Transduction of human MSCs by using different doses of adenovirus that contained a cytomegalovirus (CMV) promoter driving the mutant herpes simplex virus type 1 thymidine kinase reporter gene (Ad-CMV-HSV1-sr39tk) was characterized in a cell culture. A total of 2.25 x 10(6) transduced (n = 5) and control nontransduced (n = 5) human MSCs were injected into the myocardium of 10 rats, and reporter gene expression in human MSCs was visualized with micro-PET by using the radiotracer 9-(4-[fluorine 18]-fluoro-3-hydroxymethylbutyl)-guanine (FHBG). Different numbers of transduced human MSCs suspended in either phosphate-buffered saline (PBS) (n = 4) or matrigel (n = 5) were injected into the myocardium of nine swine, and gene expression was visualized with a clinical PET-CT. For analysis of cell culture experiments, linear regression analyses combined with a t test were performed. To test differences in radiotracer uptake between injected and remote myocardium in both rats and swine, one-sided paired Wilcoxon tests were performed. In swine experiments, a linear regression of radiotracer uptake ratio on the number of injected transduced human MSCs was performed.In cell culture, there was a viral dose-dependent increase of gene expression and FHBG accumulation in human MSCs. Human MSC viability was 96.7% (multiplicity of infection, 250). Cardiac FHBG uptake in rats was significantly elevated (P < .0001) after human MSC injection (0.0054% injected dose [ID]/g +/- 0.0007 [standard deviation]) compared with that in the remote myocardium (0.0003% ID/g +/- 0.0001). In swine, myocardial radiotracer uptake was not elevated after injection of up to 100 x 10(6) human MSCs (PBS group). In the matrigel group, signal-to-background ratio increased to 1.87 after injection of 100 x 10(6) human MSCs and positively correlated (R(2) = 0.97, P < .001) with the number of administered human MSCs.Reporter gene imaging in human MSCs can be translated to large animals. The study highlights the importance of co-administering a "scaffold" for increasing intramyocardial retention of human MSCs.
View details for DOI 10.1148/radiol.2513081616
View details for Web of Science ID 000268362900015
View details for PubMedID 19366903
View details for PubMedCentralID PMC2702468
Bone Marrow Stem Cells for the Treatment of Ischemic Heart Disease: A Clinical Trial Review
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
2009; 2 (2): 202-218
Cardiovascular disease continues to represent a significant and growing source of morbidity and mortality despite advances in traditional treatments. As a result, increasing interest and research in regenerative therapies has emerged in recent years. Among them, cell therapy represents an area of significant potential. An expanding clinical literature now exists involving the use of bone marrow-derived stem cells in the treatment of ischemic heart disease. These early studies appear to provide promising results in patient populations that include those with refractory angina, ischemic cardiomyopathy with left ventricular dysfunction, and end-stage heart failure. This review serves to provide a comprehensive examination of these clinical trials focused on several components including cell preparation, cell delivery, safety, and efficacy of these trials.
View details for DOI 10.1007/s12265-009-9095-8
View details for Web of Science ID 000284690100011
View details for PubMedID 20559989
- Reporter gene imaging following percutaneous delivery in swine - Moving toward clinical applications JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 2008; 51 (5): 595-597
Predictive value of the index of microcirculatory resistance in patients with ST-segment elevation myocardial infarction
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
2008; 51 (5): 560-565
The objective of this study is to evaluate the predictive value of the index of microcirculatory resistance (IMR) in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).Despite adequate epicardial artery reperfusion, a number of patients with STEMI have a poor prognosis because of microvascular damage. Assessing the status of the microvasculature in this setting remains challenging.In 29 patients after primary PCI for STEMI, IMR was measured with a pressure sensor/thermistor-tipped guidewire. The Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, TIMI frame count, coronary flow reserve, and ST-segment resolution were also recorded.The IMR correlated significantly with the peak creatinine kinase (CK) (R = 0.61, p = 0.0005) while the other measures of microvascular dysfunction did not. In patients with an IMR greater than the median value of 32 U, the peak CK was significantly higher compared with those having values
32 U compared with
View details for DOI 10.1016/j.jacc.2007.08.062
View details for PubMedID 18237685
Recurrent spontaneous coronary artery dissection with transient left ventricular systolic dysfunction.
International journal of cardiology
2007; 116 (2): e48-50
Spontaneous coronary artery dissection (SCAD) is a potentially life-threatening entity with a variety of clinical presentations. We report a patient who presented with chest pain and angiographic evidence of coronary dissection. Due to the rapid resolution of symptoms and benign-appearing nature of the dissection, no intervention was pursued and the patient was maintained on medical therapy. She represented 2 days later with substernal chest pain, dynamic EKG changes, positive cardiac biomarkers and a transient depression of her left ventricular function.
View details for PubMedID 16930750
Successful removal of a paradoxical coronary embolus using an aspiration catheter
NATURE CLINICAL PRACTICE CARDIOVASCULAR MEDICINE
2006; 3 (11): 633-636
A 28-year-old man presented at hospital with persistent pain in his chest and left arm, a paced rhythm on electrocardiography and elevated levels of cardiac enzymes. He was known to have patent foramen ovale and a dual-chamber pacemaker, which had been implanted following electrophysiological ablation to treat supraventricular tachycardia 3 years previously. The patient did not have a history of cardiovascular risk factors, recent travel, immobilization or clinical features of infection, and he was not taking any medication.Electrocardiography, cardiac enzyme studies, coronary angiography and transthoracic echocardiography.Acute myocardial infarction, paradoxical coronary embolus and patent foramen ovale.Coronary aspiration embolectomy and systemic anticoagulation.
View details for DOI 10.1038/ncpcardio0681
View details for Web of Science ID 000241556000012
View details for PubMedID 17063168
Cutting balloon inflation for drug-eluting stent underexpansion due to unrecognized coronary arterial calcification.
Cardiovascular revascularization medicine : including molecular interventions
2006; 7 (3): 185-188
Unrecognized calcification is a cause of stent underexpansion which significantly increases the subsequent risks of restenosis and/or stent thrombosis. We describe the use of cutting balloon inflation within the implanted stent which overcame calcific restraint unresponsive to high pressure inflations with non-compliant balloons.
View details for PubMedID 16945827
Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery - Implications for current clinical trials
2005; 112 (9): I150-I156
Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model.Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 10(7) 111indium-oxine-labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by gamma-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26+/-3% (IM), 47+/-1% (IC), and 43+/-3% (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11+/-3%) compared with IC (2.6+/-0.3%) (P<0.05) delivery. IRV delivery efficiency (3.2+/-1%) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques.The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.
View details for DOI 10.1161/CIRCULATIONAHA.104.526749
View details for Web of Science ID 000231741600023
View details for PubMedID 16159808
Brachial artery distensibility and relation to cardiovascular risk factors in healthy young adults (The Bogalusa Heart Study)
AMERICAN JOURNAL OF CARDIOLOGY
2002; 89 (8): 946-951
Arterial distensibility decreases with age and atherosclerosis leading to increased pulse pressure (PP) and increased left ventricular work, resulting in left ventricular hypertrophy, a risk factor for cardiovascular morbidity. Brachial artery pulse curve data were collected using the DynaPulse 2000A. Distensibility measured in 920 healthy young adults (40% men, 70% white, age range 18 to 38 years) was compared with levels of cardiovascular risk factors. Laboratory, anthropometric, blood pressure (BP), and heart rate measurements were also obtained. Distensibility tended to decrease with age, reaching significance in women (p <0.05). Whites had greater distensibility adjusted for age than blacks, with women more than men (p <0.05). Distensibility adjusted for PP was negatively correlated with measures of body size, BP, glucose, insulin, low-density lipoprotein cholesterol, very low density lipoprotein cholesterol, and age (p <0.05). When distensibility was plotted as a function of PP to control for distending pressure, the lowest quintiles of systolic, diastolic, and mean arterial BPs tended to have greater distensibility. No differences were seen by quintiles of lipids. In multivariate analyses, BP, age, anthropometric measures, gender, and very low density lipoprotein cholesterol entered the model (r(2) = 0.56; p <0.02). Thus, brachial artery distensibility, which includes a normalization factor to control for body size, showed race and gender differences (whites and women had greater distensibility than blacks and men, respectively), even after adjustment for age. Stiffer vessels with decreased distensibility were seen in subjects with higher levels of cardiovascular risk factors across the range of normal PP. Therefore, noninvasive measures of distensibility are useful in measuring subclinical vascular changes related to arteriosclerosis.
View details for Web of Science ID 000175091700009
View details for PubMedID 11950433
Age-based differences between mercury sphygmomanometer and pulse dynamic blood pressure measurements.
Blood pressure monitoring
1998; 3 (2): 125–29
BACKGROUND: Both the mercury sphygmomanometer and oscillometric measurement methods are widely in use for pediatric, adult, and geriatric patients. However, inherent differences between the methods of measurement may create varying degrees of sensitivity to age and potentially result in differences between measurements for these two techniques. DESIGN: Measurements of systolic and diastolic blood pressures in 154 subjects were obtained using the mercury sphygmomanometer and pulse dynamic oscillometric methods in accordance with the 1987 Association for the Advancement of Medical Instrumentation guidelines. Subjects were separated into three age groups and their data analyzed for differences between measurements for these two techniques. METHODS: Two qualified nurses derived systolic and diastolic blood pressures using phase I and phase IV Korotkoff sounds, respectively, during simultaneous monitoring with the pulse dynamic oscillometric method. RESULTS: Inter-nurse variabilities for measurement derived by mercury sphygmomanometer were 1.8 +/- 4.1 for systolic and 0.9 +/- 3.9for diastolic blood pressure. Mean differences (reference-device) of -5 +/- 5 mmHg (pulse dynamic value higher) for systolic and 1 +/- 5 mmHg (pulse dynamic value lower) for diastolic blood pressure between pulse dynamic and mercury sphygmomanometer values were found for all subjects. However, pulse dynamic systolic blood pressure was significantly higher than mercury sphygmomanometer systolic blood pressure for group 1 (n = 51, aged 11-22 years, mean difference -5.6 mmHg, P = 0.03). A similar trend was observed with group 2 (n = 51, aged 23-54 years, mean difference -4.3 mmHg, P = 0.06). We observedf no significant difference for systolic blood pressure with group 3 (n = 52, aged 55-85 years, mean difference -3.8 mmHg, P > 0.1). For all three groups we found no significant difference for diastolic blood pressure. CONCLUSION: The variation in the agreement of systolic blood pressure measurements can be attributed to the differing effects of age-dependent arterial changes on the measurement methods. The findings indicate that, although the pulse dynamic oscillometric method and mercury sphygmomanometer correlate well when patients of all ages were evaluated as a group, agreement between measurements of systolic blood pressure is dependent on age and the method of measurement employed.
View details for PubMedID 10212342
Validation of pulse dynamic blood pressure measurement by auscultation.
Blood pressure monitoring
1998; 3 (2): 121–24
BACKGROUND: The accurate measurement of arterial blood pressure is essential for the diagnosis and treatment of hypertension. The development of new automated methods of measurement that provide reliable determinations of blood pressure should be valuable in the assessment of hypertension not only in the clinic or hospital but also, in the home for self-monitoring. DESIGN: We evaluated a noninvasive method for the measurement of systolic and diastolic blood pressures in 132 subjects. METHODS: Measurements obtained using the pulse dynamic method of blood pressure determination were validated with simultaneous manual measurements. Two qualified nurses used Korotkoff sounds to determine systolic (phase I) and diastolic (phase IV) blood pressures according to the Association for the Advancement of Medical Instrumentation 1987 guidelines. RESULTS: Inter-nurse variability was 2.7 +/- 4.1 mmHg (mean +/- SD) for systolic blood pressure and 4.0 +/- 3.7 mmHg for diastolic blood pressure and correlations were r = 0.98 and 0.94, respectively. We observed excellent agreement between auscultatory and pulse dynamic methods for systolic (127 +/- 21 versus 132 +/- 20 mmHg; r = 0.97) and diastolic (72 +/- 10 versus 71 +/- 10 mmHg; r = 0.89) blood pressures. Bland-Altman analysis demonstrated that there was a mean difference (reference-device) between the two methods of - mmHg (pulse dynamic value higher) and SD of 5 mmHg for systolic blood pressure and a mean difference of 1 mmHg (pulse dynamic value lower) and SD of 5 mmHg for diastolic blood pressure. CONCLUSION: The results of this study demonstrate that this noninvasive method of measurement of blood pressure is accurate and reliable and should therefore be appropriate for the evaluation of hypertension both in the home and in clinical settings.
View details for PubMedID 10212341
Development and validation of a noninvasive method to determine arterial pressure and vascular compliance
AMERICAN JOURNAL OF CARDIOLOGY
1997; 80 (3): 323-330
The ability not only to record automated systolic and diastolic pressure, but also to derive measurements of the rate of pressure change during the cardiac cycle, would have great potential clinical value. A new method has been developed to obtain pressure measurements at 20-ms intervals by oscillometric cuff signal pattern recognition. Derivation of noninvasive pressure measurements is based on a T tube aorta and straight tube brachial artery, and assumes that the systolic phase of the suprasystolic cuff signal and the diastolic phase of the subdiastolic cuff signal most closely approximate systolic and diastolic aortic pressures, respectively. Arterial pressures obtained by this method were compared with simultaneous invasive measurements from the thoracic aorta in 36 patients. Good agreement was observed between noninvasive and invasive methods for systolic (146 +/- 4 vs 145 +/- 5 mm Hg), diastolic (80 +/- 2 vs 77 +/- 2 mm Hg), and mean (100 +/- 3 vs 100 +/- 3 mm Hg) arterial pressures, and correlation coefficients were r = 0.94, 0.91, and 0.95, respectively. To assess the validity of measurements of the rate of pressure change, oscillometric cuff signals from a subgroup of 14 patients were analyzed in detail for the peak positive pressure derivative (dP/dt(Max)), peak negative pressure derivative (dP/dt(Min)), and time interval between peak positive and peak negative pressure derivatives [t(pp)]. Results (mean +/- SEM) were: [table in text]. The incorporation of measurements of the rate of pressure change into a physical model of the brachial artery was used to derive vascular compliance. A significant correlation was observed between vascular compliance derived from the oscillometric signal and determinations by either thermodilution or Fick methods and noninvasive pressures (n = 20, r = 0.83, p <0.001). Day-to-day variability for blood pressure and vascular compliance derived by the noninvasive method did not differ by >4%, representing a reproducible measure of vascular structure and function. We conclude that the measurement of absolute pressure and rate of pressure change show good correlation with catheter data and that vascular compliance can be reliably assessed by this new method. The technology should provide a valuable noninvasive tool for the assessment of both cardiac function and vascular properties.
View details for Web of Science ID A1997XP48600012
View details for PubMedID 9264426
Arterial compliance by cuff sphygmomanometer - Application to hypertension and early changes in subjects at genetic risk
1996; 28 (4): 599-603
Abnormalities of the arterial pulse waveform reflect changes in cardiovascular structure and function. These abnormalities may occur early in the course of essential hypertension, even before the onset of blood pressure elevation. Previous studies of cardiovascular structure and function have relied on invasive intra-arterial cannulation to obtain the arterial pulse wave. We evaluated arterial structure and function using a noninvasive cuff sphygmomanometer in hypertensive (n = 15) and normotensive (n = 36) subjects stratified by genetic risk (family history) for hypertension. Using a simple physical model in which the aorta was assumed to be a T tube and the brachial artery a straight tube, we determined vascular compliance and peripheral resistance by analyzing the brachial artery pulsation signal from a cuff sphygmomanometer. Essential hypertensive subjects tended to have higher peripheral resistance (P = .06) and significantly lower vascular compliance (P = .001) than normotensive subjects. Vascular compliance correlated with simultaneously determined pulse pressure in both groups (n = 51, r = .74, P < .0001). Higher peripheral resistance (P = .07) and lower vascular compliance (P = .04) were already found in still-normotensive offspring of hypertensive parents (ie, normotensive subjects with a positive family history of hypertension) than in normotensive subjects with a negative family history of hypertension. Multivariate analysis demonstrated that both genetic risk for hypertension (P = .030) and blood pressure status (P = .041), although not age (P = .207), were significant predictors of vascular compliance (multiple R = .47, P = .011). However, by two-way ANOVA, genetic risk for hypertension was an even more significant determinant (F = 7.84, P = .007) of compliance than blood pressure status (F = 2.69, P = .089). Antihypertensive therapy with angiotensin-converting enzyme inhibitors (10 days, n = 10) improved vascular compliance (P = .02) and reduced resistance (P = .003) significantly; treatment with calcium channel antagonists (4 weeks, n = 8) tended to improve vascular compliance (P = .07) and significantly reduced peripheral resistance (P = .006). We conclude that arterial vascular compliance abnormalities detected by a noninvasive cuff sphygmomanometer reflect treatment-reversible changes in vascular structure and function. Early changes in vascular compliance in still-normotensive individuals at genetic risk for hypertension may be a heritable pathogenetic feature of this disorder.
View details for Web of Science ID A1996VL90900005
View details for PubMedID 8843884
- Corresponding pulse pressure and arterial compliance variations during ambulatory monitoring Conference on Time-Dependent Structure and Control of Arterial Blood Pressure NEW YORK ACAD SCIENCES. 1996: 310–312