Anson Lee

All Publications

• Asthma phenotypes, associated comorbidities, and long-term symptoms in COVID-19 European Journal of Allergy and Clinical Immunology Eggert, L. E., He, Z., Collins, W., Lee, A. S., Nadeau, K., Chinthrajah, R. 2021

  View details for DOI 10.1111/all.14972

• "Cheese Wire" Fenestration of Dissection Intimal Flap to Facilitate Thoracic Endovascular Aortic Repair in Chronic Dissection. Journal of vascular and interventional radiology : JVIR Iwakoshi, S., Watkins, C. A., Ogawa, Y., Fischbein, M., Lee, A., Lee, J. T., Hiesinger, W., Dake, M. D. 2019

  Abstract

  Thoracic endovascular aortic repair (TEVAR) for aneurysmal chronic dissection is often complicated by retrograde filling of the false lumen and dissected distal landing zone. A "cheese wire"-style fenestration of the dissection intimal flap can create a landing zone facilitating TEVAR. This technique successfully aided TEVAR in 3 patients with an average age of 57.3 years. Complications included type III endoleak requiring relining and renal artery occlusion requiring stent placement. Average duration of clinical follow-up was 19 ± 4 months. Imaging follow-up was 8 ± 10 months. All patients have survived for more than 1 year without aneurysm enlargement.

  View details for DOI 10.1016/j.jvir.2019.06.004

  View details for PubMedID 31542270

• Comprehensive Analysis of Differential Expressed Genes Related with Myocardial Reverse Remodeling Following HeartWare Ventricular Assist Device Implantation Shudo, Y., Jaatinen, K. J., NIshiga, M., Chen, I. Y., Greene, C. L., Koyano, T. K., Fong, R. W., Boyd, J. H., Lee, A. M., Hiesinger, W., Woo, J. ELSEVIER SCIENCE INC. 2019: S244

  View details for DOI 10.1016/j.healun.2019.01.603

  View details for Web of Science ID 000461365101285

• Impact of Surgical Approach in Double Lung Transplantation: Median Sternotomy Decreases Operative and Cardiopulmonary Bypass Time Compared to Clamshell Thoracotomy Shudo, Y., Rinewalt, D., Lingala, B., Kim, F. Y., He, H., Boyd, J. H., Lee, A. M., Hiesinger, W., Currie, M. E., MacArthur, J. W., Woo, J. ELSEVIER SCIENCE INC. 2019: S414

  View details for DOI 10.1016/j.healun.2019.01.1054

  View details for Web of Science ID 000461365103045

• Intramyocardial Injection of Mesenchymal Precursor Cells and Successful TemporaryWeaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure A Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Yau, T. M., Pagani, F. D., Mancini, D. M., Chang, H. L., Lala, A., Woo, Y., Acker, M. A., Selzman, C. H., Soltesz, E. G., Kern, J. A., Maltais, S., Charbonneau, E., Pan, S., Marks, M. E., Moquete, E. G., O'Sullivan, K. L., Taddei-Peters, W. C., McGowan, L. K., Green, C., Rose, E. A., Jeffries, N., Parides, M. K., Weisel, R. D., Miller, M. A., Hung, J., O'Gara, P. T., Moskowitz, A. J., Gelijns, A. C., Bagiella, E., Milano, C. A., Buxton, D., Geller, N. L., Gordon, D., Burke, C., Lee, A., Smith, T., Moy, C. S., Weisel, R., Cardiothoracic Surg Trials Network 2019; 321 (12): 1176–86

  View details for DOI 10.1001/jama.2019.2341

  View details for Web of Science ID 000463074900013

• Successful heart-lung-kidney and domino heart transplantation following veno-venous extracorporeal membrane oxygenation support INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY Zhu, Y., Shudo, Y., Lee, A. M., Woo, Y. 2019; 28 (2): 316–17

  View details for DOI 10.1093/icvts/ivy251

  View details for Web of Science ID 000467955400022

• Evaluation of Risk Factors for Heart-Lung Transplant Recipient Outcome: An Analysis of the United Network for Organ Sharing Database. Circulation Shudo, Y. n., Wang, H. n., Lingala, B. n., He, H. n., Kim, F. Y., Hiesinger, W. n., Lee, A. M., Boyd, J. H., Currie, M. n., Woo, Y. J. 2019; 140 (15): 1261–72

  Abstract

  Heart-lung transplantation (HLTx) is an effective treatment for patients with advanced cardiopulmonary failure. However, no large multicenter study has focused on the relationship between donor and recipient risk factors and post-HLTx outcomes. Thus, we investigated this issue using data from the United Network for Organ Sharing database.All adult patients (age ≥18 years) registered in the United Network for Organ Sharing database who underwent HLTx between 1987 and 2017 were included (n=997). We stratified the cohort by patients who were alive without retransplant at 1 year (n=664) and patients who died or underwent retransplant within 1 year of HLTx (n=333). The primary outcome was the influence of donor and recipient characteristics on 1-year post-HLTx recipient death or retransplant. Kaplan-Meier curves were created to assess overall freedom from death or retransplant. To obtain a better effect estimation on hazard and survival time, the parametric Accelerated Failure Time model was chosen to perform time-to-event modeling analyses.Overall graft survival at 1-year post-HLTx was 66.6%. Of donors, 53% were male, and the mean age was 28.2 years. Univariable analysis showed advanced donor age, recipient male sex, recipient creatinine, recipient history of prior cardiac or lung surgery, recipient extracorporeal membrane oxygenation support, transplant year, and transplant center volume were associated with 1-year post-HLTx death or retransplant. On multivariable analysis, advanced donor age (hazard ratio [HR], 1.017; P=0.0007), recipient male sex (HR, 1.701; P=0.0002), recipient extracorporeal membrane oxygenation support (HR, 4.854; P<0.0001), transplant year (HR, 0.962; P<0.0001), and transplantation at low-volume (HR, 1.694) and medium-volume centers (HR, 1.455) in comparison with high-volume centers (P=0.0007) remained as significant predictors of death or retransplant. These predictors were incorporated into an equation capable of estimating the preliminary probability of graft survival at 1-year post-HLTx on the basis of preoperative factors alone.HLTx outcomes may be improved by considering the strong influence of donor age, recipient sex, recipient hemodynamic status, and transplant center volume. Marginal donors and recipients without significant factors contributing to poor post-HLTx outcomes may still be considered for transplantation, potentially with less impact on the risk of early postoperative death or retransplant.

  View details for DOI 10.1161/CIRCULATIONAHA.119.040682

  View details for PubMedID 31589491

• Surgical Management for Aortoesophageal Fistula After Endovascular Aortic Repair. The Annals of thoracic surgery Zhu, Y. n., MacArthur, J. W., Lui, N. n., Lee, A. M. 2019

  Abstract

  This case demonstrates successful surgical management of a 6 cm-long aortoesophageal fistula from an infected stent graft. A 69-year-old woman with a penetrating descending thoracic aortic ulcer underwent endovascular aortic repair. Two weeks later, she presented with nausea and melena, and was found to have an infected stent graft on imaging. She underwent a two-stage procedure encompassing aortic arch debranching and extra-anatomic aortic bypass in stage one, and stent graft resection, primary esophageal repair, intercostal and omental flap and jejunostomy tube placement in stage two. She was discharged one month later and is doing well 1.5 years after the operation.

  View details for DOI 10.1016/j.athoracsur.2019.08.076

  View details for PubMedID 31586613

• Diagnosing Epithelioid Hemangioendothelioma With Pericardial Involvement ANNALS OF THORACIC SURGERY Balansay, B. E., Zhang, X., Loftus, P. D., Valenzuela, J., Zambrano, E., Lee, A. M. 2018; 106 (4): E173–E175

  View details for DOI 10.1016/j.athoracsur.2018.03.045

  View details for Web of Science ID 000445116100003

• Outcomes of Transcatheter Aortic Valve Replacement compared to Surgical Aortic Valve Replacement in patients with prior Chest Radiation Chacko, Y., Zhang, X., Jaluba, K., Lee, A., Miller, D., Yeung, A. C., Kim, B., Fearon, W. ELSEVIER SCIENCE INC. 2018: B244–B245

  View details for DOI 10.1016/j.jacc.2018.08.1809

  View details for Web of Science ID 000455137100602

• Ambulating femoral venoarterial extracorporeal membrane oxygenation bridge to heart-lung transplant JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Shudo, Y., Kasinpila, P., Lee, A. M., Rao, V. K., Woo, Y. 2018; 156 (3): E135–E137

  View details for DOI 10.1016/j.jtcvs.2018.03.002

  View details for Web of Science ID 000441556000001

• Successful heart-lung-kidney and domino heart transplantation following veno-venous extracorporeal membrane oxygenation support. Interactive cardiovascular and thoracic surgery Zhu, Y., Shudo, Y., Lee, A. M., Woo, Y. J. 2018

  Abstract

  A 60-year-old man with cystic fibrosis, mediastinal shift and end-stage kidney disease underwent a heart-lung-kidney transplantation. His explanted heart was used for a domino heart transplantation. This case showed an excellent outcome, even with high preoperative acuity requiring veno-venous extracorporeal membrane oxygenation and continuous veno-venous haemodialysis.

  View details for PubMedID 30113636

• Emergency valve-sparing aortic root replacement and coronary artery bypass grafting for giant left sinus of Valsalva aneurysm presenting as acute coronary syndrome JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Pedroza, A. J., Brewer, Z. E., Lee, A. M. 2018; 156 (2): E81–E84

  View details for DOI 10.1016/j.jtcvs.2018.03.009

  View details for Web of Science ID 000438731500004

• Impact of load variations on systolic function of failed left ventricle under extracorporeal membrane oxygenation assessed by strain and tissue doppler imaging Ouazani, N., Shudo, Y., Sallam, K., Lee, A., Boyd, J., Teuteberg, J. WILEY. 2018: 114–15

  View details for Web of Science ID 000434123900311

• Diagnosing Epithelioid Hemangioendothelioma with Pericardial Involvement. The Annals of thoracic surgery Balansay, B. E., Zhang, X., Loftus, P. D., Valenzuela, J. A., Zambrano, E., Lee, A. M. 2018

  Abstract

  Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor that commonly affects lung, liver, and bone. Among all known EHE cases, only 20% have a pulmonary origin, with metastases to the pericardium occurring in less than 1% of these. Due to its low prevalence, variable presentation, and unknown latency period, a thoracic EHE diagnosis can be easily missed. This case outlines the unique pathologic features of EHE in a patient with cardiovascular disease, provides further insight into diagnosing a rare tumor, and provides a better understanding of the pathophysiology and progression of thoracic EHE.

  View details for PubMedID 29689240

• PREDICTING MORTALITY WITH AORTOMITRAL CALCIFICATIONS IN 317 TAVR PATIENTS Willemink, M., Maret, E., Moneghetti, K., Kim, J., Haddad, F., Kobayashi, Y., Higashigaito, K., Yeung, A., Lee, A., Miller, D., Fischbein, M., Fearon, W., Fleischmann, D. ELSEVIER SCIENCE INC. 2018: 1591

  View details for DOI 10.1016/S0735-1097(18)32132-6

  View details for Web of Science ID 000429659703241

• Emergency valve-sparing aortic root replacement and coronary artery bypass grafting for giant left sinus of Valsalva aneurysm presenting as acute coronary syndrome. The Journal of thoracic and cardiovascular surgery Pedroza, A. J., Brewer, Z. E., Lee, A. M. 2018

  View details for PubMedID 29615334

• Ambulating femoral venoarterial extracorporeal membrane oxygenation bridge to heart-lung transplant. The Journal of thoracic and cardiovascular surgery Shudo, Y., Kasinpila, P., Lee, A. M., Rao, V. K., Woo, Y. J. 2018

  View details for PubMedID 29628344

• Increases in IGF-1 After Anti-TNF-alpha Therapy Are Associated With Bone and Muscle Accrual in Pediatric Crohn Disease JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM DeBoer, M. D., Lee, A. M., Herbert, K., Long, J., Thayu, M., Griffin, L. M., Baldassano, R. N., Denson, L. A., Zemel, B. S., Denburg, M. R., Herskovitz, R., Leonard, M. B. 2018; 103 (3): 936–45

  Abstract

  Low levels of insulinlike growth factor 1 (IGF-1) in pediatric and adolescent Crohn disease (CD) likely contribute to bone and muscle deficits.Assess changes in IGF-1 levels and associations with bone and muscle accrual following initiation of anti-tumor necrosis factor α (TNF-α) therapy in pediatric and adolescent CD.Participants (n = 75, age 5 to 21 years) with CD were enrolled in a prospective cohort study; 63 completed the 12-month visit.IGF-1 levels at baseline and 10 weeks, as well as dual-energy x-ray absorptiometry (DXA) and tibia peripheral quantitative computed tomography (pQCT) measures of bone and muscle at baseline and 12 months after initiation of anti-TNF-α therapy. Outcomes were expressed as sex-specific z scores.IGF-1 z scores increased from a median (interquartile range) of -1.0 (-1.58 to -0.17) to -0.36 (-1.04 to 0.36) over 10 weeks (P < 0.001). Lesser disease severity and systemic inflammation, as well as greater estradiol z scores (in girls), was significantly associated with greater IGF-1 z scores over time. DXA whole-body bone mineral content, leg lean mass, and total hip and femoral neck bone mineral density (BMD) z scores were low at baseline (P < 0.0001 vs reference data) and increased significantly (P < 0.001) over 12 months. Greater increases in IGF-1 z scores over 10 weeks predicted improvement in DXA bone and muscle outcomes and pQCT trabecular BMD and cortical area. Adjustment for changes in muscle mass markedly attenuated the associations between IGF-1 levels and bone outcomes.Short-term improvements in IGF-1 z scores predicted recovery of bone and muscle outcomes following initiation of anti-TNF-α therapy in pediatric CD. These data suggest that disease effects on growth hormone metabolism contribute to musculoskeletal deficits in CD.

  View details for PubMedID 29329430

• Video-assisted thoracoscopic surgery to displace the phrenic nerve during endocardial ablation of right atrial tachycardia. HeartRhythm case reports Mesquita, J. n., Bisla, J. n., Lee, A. n., Perez, M. n. 2018; 4 (7): 304–6

  View details for PubMedID 30023277

• Prolonged survival of transplanted stem cells after ischaemic injury via the slow release of pro-survival peptides from a collagen matrix Nature Biomedical Engineering Lee, A. S., Inayathullah, ., Lijkwan, . A., Zhao, X., Sun, W., Park, S., Hong, W. X., Parekh, M. B., Malkovskiy, A. V., Lau, E., Qin, X., Pothineni,, . R., Sanchez-Freire, ., Kooreman, N. G., Ebert, A. D., Chan, C. K., Nguyen, P. K., Rajadas, J., Wu, J. C. 2018; 2 (2): 104–13

  Abstract

  Stem-cell-based therapies hold considerable promise for regenerative medicine. However, acute donor-cell death within several weeks after cell delivery remains a critical hurdle for clinical translation. Co-transplantation of stem cells with pro-survival factors can improve cell engraftment, but this strategy has been hampered by the typically short half-lives of the factors and by the use of Matrigel and other scaffolds that are not chemically defined. Here, we report a collagen-dendrimer biomaterial crosslinked with pro-survival peptide analogues that adheres to the extracellular matrix and slowly releases the peptides, significantly prolonging stem cell survival in mouse models of ischaemic injury. The biomaterial can serve as a generic delivery system to improve functional outcomes in cell-replacement therapy.

  View details for DOI 10.1038/s41551-018-0191-4

  View details for PubMedCentralID PMC5927627

• Complex EVAR Is Associated With Higher Perioperative Mortality but Not Late-Mortality Compared to Infrarenal EVAR Amongst Octogenarians Tran, K., Lee, A., McFarland, G., Sgroi, M., Itoga, N., Lee, J. MOSBY-ELSEVIER. 2017: E47

  View details for Web of Science ID 000412559500008

• THE INFLAMMASOME PATHWAY IS ASSOCIATED WITH ADVERSE VENTRICULAR REMODELING FOLLOWING TRANSCATHETER AORTIC VALVE REPLACEMENT Kim, J., Kobayashi, Y., Kouznetsova, T., Moneghetti, K., Brenner, D., O'Malley, R., Dao, C., Schnittger, I., Liang, D., Wu, J., Fischbein, M., Lee, A., Miller, D., Yeung, A., Fearon, W., Haddad, F. ELSEVIER SCIENCE INC. 2017: 1040

  View details for Web of Science ID 000397342301562

• Acute Right Ventricular Failure After Successful Opening of Chronic Total Occlusion in Right Coronary Artery Caused by a Large Intramural Hematoma. Circulation. Cardiovascular interventions Kawana, M., Lee, A. M., Liang, D. H., Yeung, A. C. 2017; 10 (2)

  View details for DOI 10.1161/CIRCINTERVENTIONS.116.004674

  View details for PubMedID 28115374

• Acute Right Ventricular Failure After Successful Opening of Chronic Total Occlusion in Right Coronary Artery Caused by a Large Intramural Hematoma CIRCULATION-CARDIOVASCULAR INTERVENTIONS Kawana, M., Lee, A. M., Liang, D. H., Yeung, A. C. 2017; 10 (2)

  View details for DOI 10.1161/CIRCINTERVENTIONS.116.004674

  View details for Web of Science ID 000394542300009

• miR-25 Tough Decoy Enhances Cardiac Function in Heart Failure. Molecular therapy : the journal of the American Society of Gene Therapy Jeong, D. n., Yoo, J. n., Lee, P. n., Kepreotis, S. V., Lee, A. n., Wahlquist, C. n., Brown, B. D., Kho, C. n., Mercola, M. n., Hajjar, R. J. 2017

  Abstract

  MicroRNAs are promising therapeutic targets, because their inhibition has the potential to normalize gene expression in diseased states. Recently, our group found that miR-25 is a key SERCA2a regulating microRNA, and we showed that multiple injections of antagomirs against miR-25 enhance cardiac contractility and function through SERCA2a restoration in a murine heart failure model. However, for clinical application, a more stable suppressor of miR-25 would be desirable. Tough Decoy (TuD) inhibitors are emerging as a highly effective method for microRNA inhibition due to their resistance to endonucleolytic degradation, high miRNA binding affinity, and efficient delivery. We generated a miR-25 TuD inhibitor and subcloned it into a cardiotropic AAV9 vector to evaluate its efficacy. The AAV9 TuD showed selective inhibition of miR-25 in vitro cardiomyoblast culture. In vivo, AAV9-miR-25 TuD delivered to the murine pressure-overload heart failure model selectively decreased expression of miR-25, increased levels of SERCA2a protein, and ameliorated cardiac dysfunction and fibrosis. Our data indicate that miR-25 TuD is an effective long-term suppressor of miR-25 and a promising therapeutic candidate to treat heart failure.

  View details for PubMedID 29273502

• Successful Minimally Invasive Surgical Ablation of Atrial Fibrillation: A Call to Do Better. Circulation. Arrhythmia and electrophysiology Lee, A. M. 2017; 10 (11)

  View details for PubMedID 29138144

• Percutaneous Image-Guided Cryoablation of Musculoskeletal Metastases: Pain Palliation and Local Tumor Control. Journal of vascular and interventional radiology : JVIR Wallace, A. N., McWilliams, S. R., Connolly, S. E., Symanski, J. S., Vaswani, D., Tomasian, A., Vyhmeister, R., Lee, A. M., Madaelil, T. P., Hillen, T. J., Jennings, J. W. 2016; 27 (12): 1788-1796

  Abstract

  To evaluate the safety and effectiveness of cryoablation of musculoskeletal metastases in terms of achieving pain palliation and local tumor control.A retrospective review was performed of 92 musculoskeletal metastases in 56 patients treated with percutaneous image-guided cryoablation. Mean age of the cohort was 53.9 y ± 15.1, and cohort included 48% (27/56) men. Median tumor volume was 13.0 cm3 (range, 0.5-577.2 cm3). Indications for treatment included pain palliation (41%; 38/92), local tumor control (15%; 14/92), or both (43%; 40/92). Concurrent cementoplasty was performed after 28% (26/92) of treatments.In 78 tumors treated for pain palliation, median pain score before treatment was 8.0. Decreased median pain scores were reported 1 day (6.0; P < .001, n = 62), 1 week (5.0; P < .001, n = 70), 1 month (5.0; P < .001, n = 63), and 3 months (4.5; P = .01, n = 28) after treatment. The median pain score at 6-month follow-up was 7.5 (P = .33, n = 11). Radiographic local tumor control rates were 90% (37/41) at 3 months, 86% (32/37) at 6 months, and 79% (26/33) at 12 months after treatment. The procedural complication rate was 4.3% (4/92). The 3 major complications included 2 cases of hemothorax and 1 transient foot drop.Cryoablation is an effective treatment for palliating painful musculoskeletal metastases and achieving local tumor control.

  View details for DOI 10.1016/j.jvir.2016.07.026

  View details for PubMedID 27745968

• Baseline growth differentiation factor 15 (GDF15) is an independent predictor of reverse left atrial remodeling and mortality at 1-year following Transcatheter Aortic Valve Replacement Kim, J., Kobayashi, Y., Brenner, D., Moneghetti, K., O'Malley, R., Dao, C., Vu, T., Schnittger, I., Liang, D., Wu, J., Fischbein, M., Lee, A., Miller, D., Yeung, A., Haddad, F., Fearon, W. ELSEVIER SCIENCE INC. 2016: B298

  View details for DOI 10.1016/j.jacc.2016.09.150

  View details for Web of Science ID 000398590400257

• Basic Cardiac Electrophysiology and Common Drug-induced Arrhythmias. Critical care nursing clinics of North America Lee, A., Pickham, D. 2016; 28 (3): 357-371

  Abstract

  Drugs can be a double-edged sword, providing the benefit of symptom alleviation and disease modification but potentially causing harm from adverse cardiac arrhythmic events. Proarrhythmia is the ability of a drug to cause an arrhythmia, the number one reason for drugs to be withdrawn from the patient. Drug-induced arrhythmias are defined as the production of de novo arrhythmias or aggravation of existing arrhythmias, as a result of previous or concomitant pharmacologic treatment. This review summarizes normal cardiac cell and tissue functioning and provides an overview of drugs that effect cardiac repolarization and the adverse effects of commonly administered antiarrhythmics.

  View details for DOI 10.1016/j.cnc.2016.04.007

  View details for PubMedID 27484663

• Maze permutations during minimally invasive mitral valve surgery. Annals of cardiothoracic surgery Lee, A. M. 2015; 4 (5): 463-468

  Abstract

  Surgical ablation for atrial fibrillation is most frequently done in the concomitant setting, and most commonly with mitral valve surgery. Minimally invasive surgical techniques for the treatment of atrial fibrillation have developed contemporaneously with techniques for minimally invasive mitral valve surgery. As in traditional surgery for atrial fibrillation, there are many different permutations of ablations for the less invasive approaches. Lesion sets can vary from simple pulmonary vein isolation (PVI) to full bi-atrial lesions that completely reproduce the traditional cut-and-sew Cox Maze III procedure with variable efficacy in restoring sinus rhythm. Additionally, treatment of the atrial appendage can be done through minimally invasive approaches without any ablation at all in an attempt to mitigate the risk of stroke. Finally, hybrid procedures combining minimally invasive surgery and catheter-based ablation are being developed that might augment surgical treatment of atrial fibrillation at the time of minimally invasive mitral valve repair. These various permutations and their results are reviewed.

  View details for DOI 10.3978/j.issn.2225-319X.2015.09.07

  View details for PubMedID 26539352

  View details for PubMedCentralID PMC4598463

• Proteomic Profiling of Early Chronic Pulmonary Hypertension: Evidence for Both Adaptive and Maladaptive Pathology. Journal of pulmonary & respiratory medicine Aziz, A., Lee, A. M., Ufere, N. N., Damiano, R. J., Townsend, R. R., Moon, M. R. 2015; 5 (1)

  Abstract

  The molecular mechanisms governing right atrial (RA) and ventricular (RV) hypertrophy and failure in chronic pulmonary hypertension (CPH) remain unclear. The purpose of this investigation was to characterize RA and RV protein changes in CPH and determine their adaptive versus maladaptive role on hypertrophic development.Nine dogs underwent sternotomy and RA injection with 3 mg/kg dehydromonocrotaline (DMCT) to induce CPH (n=5) or sternotomy without DMCT (n=4). At 8-10 weeks, RA and RV proteomic analyses were completed after trypsinization of cut 2-D gel electrophoresis spots and peptide sequencing using mass spectrometry.In the RV, 13 protein spots were significantly altered with DMCT compared to Sham. Downregulated RV proteins included contractile elements: troponin T and C (-1.6 fold change), myosin regulatory light chain 2 (-1.9), cellular energetics modifier: fatty-acid binding protein (-1.5), and (3) ROS scavenger: superoxide dismutase 1 (-1.7). Conversely, beta-myosin heavy chain was upregulated (+1.7). In the RA, 22 proteins spots were altered including the following downregulated proteins contractile elements: tropomyosin 1 alpha chain (-1.9), cellular energetic proteins: ATP synthase (-1.5), fatty-acid binding protein (-2.5), and (3) polyubiquitin (-3.5). Crystallin alpha B (hypertrophy inhibitor) was upregulated in both the RV (+2.2) and RA (+2.6).In early stage hypertrophy there is adaptive upregulation of major RA and RV contractile substituents and attenuation of the hypertrophic response. However, there are multiple indices of maladaptive pathology including considerable cellular stress associated with aberrancy of actin machinery activity, decreased efficiency of energy utilization, and potentially decreased protein quality control.

  View details for DOI 10.4172/2161-105X.1000241

  View details for PubMedID 26246959

  View details for PubMedCentralID PMC4523278

• Quantification of the functional consequences of atrial fibrillation and surgical ablation on the left atrium using cardiac magnetic resonance imaging EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY Robertson, J. O., Lee, A. M., Voeller, R. K., Damiano, M. S., Schuessler, R. B., Damiano, R. J. 2014; 46 (4): 720-728

  Abstract

  The effect of atrial fibrillation (AF) on left atrial (LA) function has not been well defined and has been largely based on limited echocardiographic evaluation. This study examined the effect of AF and a subsequent Cox-Maze IV (CMIV) procedure on atrial function.Cardiac magnetic resonance imaging (cMRI) was performed in 20 healthy volunteers, 8 patients with paroxysmal atrial fibrillation (PAF) and 7 patients with persistent or long-standing persistent atrial fibrillation (LSP AF). Six of the PAF patients underwent surgical ablation with the CMIV procedure and 5 underwent both pre- and postoperative cMRIs. The persistent or LSP AF patients underwent only postoperative cMRIs because all scans were performed with patients in normal sinus rhythm. Volume-time curves throughout the cardiac cycle and regional wall shortening were evaluated using the cine images and compared across groups.Compared with normal volunteers, patients with PAF had significantly decreased reservoir contribution to left ventricular (LV) filling (P = 0.0010), an increased conduit function contribution (P = 0.04) and preserved booster pump function (P = 0.14). Following the CMIV procedure, significant reductions were noted with respect to reservoir and booster pump function, with corresponding increases in conduit function. These differences were more drastic in patients with persistent/LSP AF. Regional wall motion was significantly reduced by PAF in all wall segments (P < 0.05), but was not further reduced by the CMIV. Despite changes in LA function, LV function was preserved following surgery.PAF significantly altered LA function and has a detrimental effect on regional wall motion. Surgical intervention further altered LA function, but the reasons for this are likely multifactorial and not entirely related to the lesion set itself.

  View details for DOI 10.1093/ejcts/ezt656

  View details for Web of Science ID 000344968500024

  View details for PubMedID 24523494

  View details for PubMedCentralID PMC4271083

• Importance of atrial surface area and refractory period in sustaining atrial fibrillation: Testing the critical mass hypothesis JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Lee, A. M., Aziz, A., Didesch, J., Clark, K. L., Schuessler, R. B., Damiano, R. J. 2013; 146 (3): 593-598

  Abstract

  The critical mass hypothesis for atrial fibrillation (AF) was proposed in 1914; however, there have been few studies defining the relationship between atrial surface area and AF. This study evaluated the effect of tissue area and effective refractory period (ERP) on the probability of sustaining AF in an in vivo model.Domestic pigs (n = 9) underwent median sternotomy. Epicardial activation maps were constructed from bipolar electrograms recorded from form-fitting electrode templates placed on the atria. Baseline ERPs were determined. ERP was lowered with a continuous infusion of acetylcholine (0.005-0.04 mg/Kg/min) until AF could be sustained after burst pacing. The atria were sequentially partitioned using bipolar radiofrequency ablation. ERPs were lowered using acetylcholine until AF could be sustained in each subdivision of atrial tissue. Each subdivision was further divided until AF was no longer inducible. At study completion, the heart was excised and the surface area of each section was measured.Over a range of ERPs from 75 to 250 ms, the probability of AF was correlated with increasing tissue area (range, 19.5-105 cm(2)) and decreasing ERP. Logistic regression analysis identified shorter ERP (P < .001) and larger area (P = .006) as factors predictive of an increased probability of sustained AF (area under the curve of the receiver-operator characteristic = 0.878).The probability of sustained AF was significantly associated with increasing tissue area and decreasing ERP. These data may lead to a greater understanding of the mechanism of AF and help to design better interventional procedures.

  View details for DOI 10.1016/j.jtcvs.2012.04.021

  View details for Web of Science ID 000323605800023

  View details for PubMedID 22995722

  View details for PubMedCentralID PMC3966059

• Differential calcium handling in two canine models of right ventricular pressure overload JOURNAL OF SURGICAL RESEARCH Moon, M. R., Aziz, A., Lee, A. M., Moon, C. J., Okada, S., Kanter, E. M., Yamada, K. A. 2012; 178 (2): 554-562

  Abstract

  The purpose of this investigation was to characterize differential right atrial (RA) and ventricular (RV) molecular changes in Ca(2+)-handling proteins consequent to RV pressure overload and hypertrophy in two common, yet distinct models of pulmonary hypertension: dehydromonocrotaline (DMCT) toxicity and pulmonary artery (PA) banding.A total of 18 dogs underwent sternotomy in four groups: (1) DMCT toxicity (n = 5), (2) mild PA banding over 10 wk to match the RV pressure rise with DMCT (n = 5); (3) progressive PA banding to generate severe RV overload (n = 4); and (4) sternotomy only (n = 4).In the right ventricle, with DMCT, there was no change in sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) or phospholamban (PLB), but we saw a trend toward down-regulation of phosphorylated PLB at serine-16 (p[Ser-16]PLB) (P = 0.07). Similarly, with mild PA banding, there was no change in SERCA or PLB, but p(Ser-16)PLB was down-regulated by 74% (P < 0.001). With severe PA banding, there was no change in PLB, but SERCA fell by 57% and p(Ser-16)PLB fell by 67% (P < 0.001). In the right atrium, with DMCT, there were no significant changes. With both mild and severe PA banding, p(Ser-16)PLB fell (P < 0.001), but SERCA and PLB did not change.Perturbations in Ca(2+)-handling proteins depend on the degree of RV pressure overload and the model used to mimic the RV effects of pulmonary hypertension. They are similar, but blunted, in the atrium compared with the ventricle.

  View details for DOI 10.1016/j.jss.2012.04.066

  View details for Web of Science ID 000311090700009

  View details for PubMedID 22632938

  View details for PubMedCentralID PMC3430801

• Congenital fistula from the left main coronary artery to the left atrium presenting with an acute myocardial infarction JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Anastacio, M. M., Lee, A. M., Lawton, J. S. 2012; 144 (6): E147-E148

  View details for DOI 10.1016/j.jtcvs.2012.09.015

  View details for Web of Science ID 000311086600002

  View details for PubMedID 23040318

• Evaluation of a novel cryoablation system: in vivo testing in a chronic porcine model. Innovations (Philadelphia, Pa.) Weimar, T., Lee, A. M., Ray, S., Schuessler, R. B., Damiano, R. J. 2012; 7 (6): 410-416

  Abstract

  Cryoablation is commonly used at present in the surgical treatment of atrial fibrillation (AF). However, there have been few studies examining the efficacy of the commonly used ablation devices. This report compares the efficacy of two cryoprobes in creating transmural endocardial lesions on the beating heart in a porcine model for chronic AF.In six Hanford miniature swine, the right atrial appendage and the inferior vena cava were isolated using a bipolar radiofrequency clamp to create areas of known conduction block. A connecting ablation line was performed endocardially via a purse string with the novel malleable 10-cm Cryo1 probe for 2 minutes at -40°C. Additional ablation lines were created with the Cryo1 and the 3.5-cm 3011 Maze Linear probe on the right and the left atrial wall. Epicardial activation mapping was performed before and immediately after ablation as well as 14 days postoperatively. Histologic examination was performed 14 days postoperatively.Transmural lesions were confirmed in 83/84 cross-sections (99%) for the Cryo1 probe and in 40/41 cross-sections (98%) for the 3011 Maze Linear probe. There was no difference between the devices in lesion width (mean ± SD, Cryo1, 10.7 ± 3.5 mm; 3011, 10.0 ± 3.9 mm; P = 0.31), lesion depth (Cryo1, 4.5 ± 1.7 mm; 3011, 4.6 ± 1.5 mm; P = 0.74), or atrial wall thickness (Cryo1, 4.5 ± 1.8 mm; 3011, 4.7 ± 1.7 mm; P = 0.74). There was a conduction delay across the right atrial ablation line (20 ± 2 milliseconds vs 51 ± 8 milliseconds, P < 0.001) that remained unchanged at 14 days (51 ± 8 milliseconds vs 52 ± 10 milliseconds, P = 0.88).The Cryo1 probe created transmural lesions on the beating heart, resulting in sustained conduction delay. Both probes had a similar performance in lesion geometry in this chronic animal model.

  View details for DOI 10.1097/IMI.0b013e31828534e5

  View details for PubMedID 23422803

  View details for PubMedCentralID PMC3578219

• Evaluation of a novel cryoablation system: in vitro testing of heat capacity and freezing temperatures. Innovations (Philadelphia, Pa.) Weimar, T., Lee, A. M., Ray, S., Schuessler, R. B., Damiano, R. J. 2012; 7 (6): 403-409

  Abstract

  Cryoablation has been used to ablate cardiac tissue for decades and has been shown to be able to replace incisions in the surgical treatment of atrial fibrillation. This in vitro study evaluates the performance of a novel cryoprobe and compares it with existing commercially available devices.A new malleable 10-cm aluminum cryoprobe was compared with a rigid 3.5-cm copper linear probe using in vitro testing to evaluate performances under different thermal loads and with different tissue thicknesses. Radial dimensions of ice formation were measured in each water bath by a high-precision laser 2 minutes after the onset of cooling. Probe-surface temperatures were recorded by thermocouples. Tissue temperature was measured at depths of 4 mm and 5 mm from the probe-tissue interface. Time to reach a tissue temperature of -20°C was recorded.Ice formation increased significantly with lower water-bath temperatures (P < 0.001). Width and depth of ice formation were significantly less for the rigid linear probe (P < 0.012 and P < 0.001, respectively). There was no difference between the probes in the maximal negative temperature reached under different thermal loads or at different tissue depths. The malleable probe achieved significantly lower temperatures at the proximal compared with the distal end (-61.7°C vs -55.0°C, respectively; P < 0.001). A tissue temperature of -20°C was reached earlier at 4 mm than at 5 mm (P < 0.001) and was achieved significantly faster with the 3011 Maze Linear probe (P < 0.021).The new malleable probe achieved rapid freezing to clinically relevant levels in up to 5-mm-thick tissue. Both probes maintained their performance under a wide range of thermal loads.

  View details for DOI 10.1097/IMI.0b013e3182853e74

  View details for PubMedID 23422802

  View details for PubMedCentralID PMC3578216

• Chronic performance of a novel radiofrequency ablation device on the beating heart: Limitations of conduction delay to assess transmurality JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Lee, A. M., Aziz, A., Clark, K. L., Schuessler, R. B., Damiano, R. J. 2012; 144 (4): 859-865

  Abstract

  The creation of consistently transmural lesions with epicardial ablation on the beating heart has represented a significant challenge for current technology. This study examined the chronic performance of the AtriCure Coolrail device (AtriCure Inc, West Chester, Ohio), an internally cooled, bipolar radiofrequency ablation device designed for off-pump epicardial ablation. The study also examined the reliability of using acute intraoperative conduction delay to evaluate lesion integrity.Seven swine underwent median sternotomy. The right atrial appendage and inferior vena cava were isolated with a bipolar radiofrequency clamp. Linear ablation lines were created between these structures with the AtriCure Coolrail. Paced activation maps were recorded with epicardial patch electrodes acutely before and after ablation and after keeping the animals alive for 4 weeks. The conduction time across the linear ablation was calculated from these maps. The lesions were histologically evaluated with trichrome staining.Only 76% of cross-sections of Coolrail lesions were transmural, and only 1 of 12 ablation lines was transmural in every cross-section examined. Mapping data were available in 5 of the animals. Significant conduction delay was present after the creation of each line of ablation acutely; however, after 4 weeks, conduction time returned to preablation values, demonstrating lack of transmurality.The AtriCure Coolrail failed to reliably create transmural lesions. Although the Coolrail was able to create acute conduction delay, its failure to transmurally ablate the atrial myocardium left gaps along the length of the lesion, which resulted in neither chronic conduction block nor delay across any line of ablation.

  View details for DOI 10.1016/j.jtcvs.2012.01.001

  View details for Web of Science ID 000309111600020

  View details for PubMedID 22305553

  View details for PubMedCentralID PMC3966079

• Patient-Specific Induced Pluripotent Stem Cells as a Model for Familial Dilated Cardiomyopathy SCIENCE TRANSLATIONAL MEDICINE Sun, N., Yazawa, M., Liu, J., Han, L., Sanchez-Freire, V., Abilez, O. J., Navarrete, E. G., Hu, S., Wang, L., Lee, A., Pavlovic, A., Lin, S., Chen, R., Hajjar, R. J., Snyder, M. P., Dolmetsch, R. E., Butte, M. J., Ashley, E. A., Longaker, M. T., Robbins, R. C., Wu, J. C. 2012; 4 (130)

  Abstract

  Characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure, dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy in patients. DCM is the most common diagnosis leading to heart transplantation and places a significant burden on healthcare worldwide. The advent of induced pluripotent stem cells (iPSCs) offers an exceptional opportunity for creating disease-specific cellular models, investigating underlying mechanisms, and optimizing therapy. Here, we generated cardiomyocytes from iPSCs derived from patients in a DCM family carrying a point mutation (R173W) in the gene encoding sarcomeric protein cardiac troponin T. Compared to control healthy individuals in the same family cohort, cardiomyocytes derived from iPSCs from DCM patients exhibited altered regulation of calcium ion (Ca(2+)), decreased contractility, and abnormal distribution of sarcomeric α-actinin. When stimulated with a β-adrenergic agonist, DCM iPSC-derived cardiomyocytes showed characteristics of cellular stress such as reduced beating rates, compromised contraction, and a greater number of cells with abnormal sarcomeric α-actinin distribution. Treatment with β-adrenergic blockers or overexpression of sarcoplasmic reticulum Ca(2+) adenosine triphosphatase (Serca2a) improved the function of iPSC-derived cardiomyocytes from DCM patients. Thus, iPSC-derived cardiomyocytes from DCM patients recapitulate to some extent the morphological and functional phenotypes of DCM and may serve as a useful platform for exploring disease mechanisms and for drug screening.

  View details for DOI 10.1126/scitranslmed.3003552

  View details for Web of Science ID 000303045900004

  View details for PubMedID 22517884

  View details for PubMedCentralID PMC3657516

• Cardiac Surgery The Washington ManualTM of Surgery Lee, A., Damiano, Jr, R. edited by Aziz, A., Bharat, A., Fox, A., Porembka, M. Lippincott, Williams & Wilkins, Philadelphia. 2012; 6th: 695–722
• Surgical ablation of atrial fibrillation Electrophysiological Disorders of the Heart Lee, A., Voeller , R., Damiano, Jr, R. edited by Saksena , S., Camm, A. Elsevier, Philadelphia. 2011; 2nd: 1415–1424
• A minimally invasive cox-maze procedure: operative technique and results. Innovations (Philadelphia, Pa.) Lee, A. M., Clark, K., Bailey, M. S., Aziz, A., Schuessler, R. B., Damiano, R. J. 2010; 5 (4): 281-286

  Abstract

  The Cox-Maze procedure (CMP) for the surgical treatment of atrial fibrillation (AF) traditionally has required a median sternotomy and cardiopulmonary bypass. This study describes a method using ablation technologies to create the full Cox-Maze lesion set through a 5- to 6-cm right minithoracotomy.Twenty-two consecutive patients underwent a CMP through a right mini-thoracotomy and cardiopulmonary bypass. All patients were followed prospectively with electrocardiogram and 24-hour Holter monitoring at 3, 6, and 12 months. The CMP lesion set was created using bipolar radiofrequency energy and cryotherapy.There was no operative mortality or major complications.Two patients required a permanent pacemaker. Five patients (23%) had early atrial tachyarrhythmias. At last follow-up(mean, 18 ± 12 months), all the patients (n=22) were free from atrial dysrhythmias. At 3 months (n=19), 84% of patients were off antiarrhythmic drugs. At 6 months (n=18), 94% of patients were free from AF and off antiarrhythmic medications. At 12 months (n=16), 81% of patients were free from AF and off antiarrhythmic drugs and three patients remained on warfarin for a mechanical mitral valve.A full CMP can be performed through a right mini-thoracotomy with outstanding short-term results. This less invasive procedure can be offered to patients without compromising efficacy.

  View details for DOI 10.1097/IMI.0b013e3181ee3815

  View details for PubMedID 21057605

  View details for PubMedCentralID PMC2967773

• Vagal denervation and reinnervation after ablation of ganglionated plexi JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Sakamoto, S., Schuessler, R. B., Lee, A. M., Aziz, A., Lall, S. C., Damiano, R. J. 2010; 139 (2): 444-452

  Abstract

  Surgical ablation of ganglionated plexi has been proposed to increase efficacy of surgery for atrial fibrillation. This experimental canine study examined electrophysiologic attenuation and recovery of atrial vagal effects after ganglionated plexi ablation alone or with standard surgical lesion sets for atrial fibrillation.Dogs were divided into 3 groups: group 1 (n = 6) had focal ablation of the 4 major epicardial ganglionated plexi fat pads, group 2 (n = 6) had pulmonary vein isolation with ablation, and group 3 (n = 6) had posterior left atrial isolation with ablation. All fat pads were ablated. Sinus and atrioventricular interval changes during bilateral vagosympathetic trunk stimulation were examined before and both immediately and 4 weeks after ablation. Vagally induced effective refractory period changes and mean QRST area changes (index of local innervation) were examined in 5 atrial regions.Sinus and atrioventricular interval changes and heart rate variability decreased immediately after ablation, but only sinus interval changes were restored significantly after 4 weeks in all groups. Ablation-modified vagal effects on effective refractory period or QRST area changed heterogeneously in groups 1 and 2. In group 3, regional vagal effects were attenuated extensively postablation in both atria. Posterior left atrial isolation with ablation incrementally denervated the atria. In the long term, vagal stimulation increased QRST area changes relative to control values in all groups. Heart rate variability was also assessed.Ganglionated plexi ablation significantly reduced atrial vagal innervation. Restoration of vagal effects at 4 weeks suggests early atrial reinnervation.

  View details for DOI 10.1016/j.jtcvs.2009.04.056

  View details for Web of Science ID 000274014300026

  View details for PubMedID 19740492

  View details for PubMedCentralID PMC2813372

• Complications after Atrial Fibrillation Surgery Complications in Cardiothoracic Surgery: Avoidance and Treatment Lee, A., Damiano, Jr, R. edited by Little, A., Merrill , W. Wiley-Blackwell, London. 2010; 2nd: 404–418
• Animal studies of epicardial atrial ablation HEART RHYTHM Schuessler, R. B., Lee, A. M., Melby, S. J., Voeller, R. K., Gaynor, S. L., Sakamoto, S., Damiano, R. J. 2009; 6 (12): S41-S45

  Abstract

  The Cox maze procedure is an effective treatment of atrial fibrillation, with a long-term freedom from recurrence greater than 90%. The original procedure was highly invasive and required cardiopulmonary bypass. Modifications of the procedure that eliminate the need for cardiopulmonary bypass have been proposed, including use of alternative energy sources to replace cut-and-sew lesions with lines of ablation made from the epicardium on the beating heart. This has been challenging because atrial wall muscle thickness is extremely variable, and the muscle can be covered with an epicardial layer of fat. Moreover, the circulating intracavitary blood acts as a potential heat sink, making transmural lesions difficult to obtain. In this report, we summarize the use of nine different unidirectional devices (four radiofrequency, two microwave, two lasers, one cryothermic) for creating continuous transmural lines of ablation from the atrial epicardium in a porcine model. We define a unidirectional device as one in which all the energy is applied by a single transducer on a single heart surface. The maximum penetration of any device was 8.3 mm. All devices except one, the AtriCure Isolator pen, failed to penetrate 2 mm in some nontransmural sections. Future development of unidirectional energy sources should be directed at increasing the maximum depth and the consistency of penetration.

  View details for DOI 10.1016/j.hrthm.2009.07.028

  View details for Web of Science ID 000276186900007

  View details for PubMedID 19959142

  View details for PubMedCentralID PMC2907672

• Evaluation of Revascularization Subtypes in Octogenarians Undergoing Coronary Artery Bypass Grafting CIRCULATION Aziz, A., Lee, A. M., Pasque, M. K., Lawton, J. S., Moazami, N., Damiano, R. J., Moon, M. R. 2009; 120 (11): S65-S69

  Abstract

  Recent data suggest that octogenarians' long-term survival after complete coronary artery bypass graft revascularization is superior to incomplete revascularization. Discriminating between variable definitions of "complete" complicates interpretation of survival data. We aimed to clarify octogenarian long-term survival rates by stratifying revascularization subtypes.From 1986 to 2007, 580 patients 80 to 94 years of age underwent coronary artery bypass graft. Functional complete revascularization was defined as at least 1 graft to all diseased coronary vessels with >50% stenosis. Traditional complete revascularization was defined as 1 graft to each major arterial system with at least 50% stenosis. Incomplete revascularization was defined as leaving diseased, ungrafted regions. Revascularization was functional in 279 (48%), traditional in 181 (31%), and incomplete in 120 (21%). Long-term survival was evaluated by Kaplan-Meier analysis. Of 537 operative survivors, there were 402 late deaths. Cumulative long-term survival totaled 2890 patient-years. Late survival (Kaplan-Meier) was similar between functional (mean, 6.8 years) and traditional (6.7 years) groups (P=0.51), but diminished with incomplete (4.2 years) revascularization (P=0.007). Survival by group at 5 years was: 59+/-3% functional, 57+/-4% traditional, and 45+/-5% incomplete. Survival at 8 years was: 40+/-3% functional, 37+/-4% traditional, and 26+/-5% incomplete. To minimize selection bias in patients with limited life expectancy, Kaplan-Meier analysis was repeated including only patients with survival >12 months. Survival was again impaired with incomplete revascularization (P=0.04), and there was no difference between functional and traditional complete revascularization (P=0.73).Bypassing all diseased arterial vessels after revascularization does not afford significant long-term survival advantage compared to a traditional approach. Incomplete revascularization, related to more extensive disease, is associated with an 18% decline in survival. These data suggest that it is important to avoid incomplete revascularization in octogenarians, but the supplementary endeavor required to perform functional complete revascularization does not improve survival.

  View details for DOI 10.1161/CIRCULATIONAHA.108.844316

  View details for Web of Science ID 000269773000010

  View details for PubMedID 19752388

  View details for PubMedCentralID PMC2752867

• Feeder-free derivation of induced pluripotent stem cells from adult human adipose stem cells PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Sun, N., Panetta, N. J., Gupta, D. M., Wilson, K. D., Lee, A., Jia, F., Hu, S., Cherry, A. M., Robbins, R. C., Longaker, M. T., Wu, J. C. 2009; 106 (37): 15720-15725

  Abstract

  Ectopic expression of transcription factors can reprogram somatic cells to a pluripotent state. However, most of the studies used skin fibroblasts as the starting population for reprogramming, which usually take weeks for expansion from a single biopsy. We show here that induced pluripotent stem (iPS) cells can be generated from adult human adipose stem cells (hASCs) freshly isolated from patients. Furthermore, iPS cells can be readily derived from adult hASCs in a feeder-free condition, thereby eliminating potential variability caused by using feeder cells. hASCs can be safely and readily isolated from adult humans in large quantities without extended time for expansion, are easy to maintain in culture, and therefore represent an ideal autologous source of cells for generating individual-specific iPS cells.

  View details for DOI 10.1073/pnas.0908450106

  View details for Web of Science ID 000269806600040

  View details for PubMedID 19805220

  View details for PubMedCentralID PMC2739869

• The surgical treatment of atrial fibrillation. The Surgical clinics of North America Lee, A. M., Melby, S. J., Damiano, R. J. 2009; 89 (4): 1001-20, x-xi

  Abstract

  Atrial fibrillation is a complex disease affecting a significant portion of the general population. Although medical therapy is the mainstay of treatment, intervention plays an important role in selected patients. The Cox-Maze procedure is the gold standard for the surgical treatment of atrial fibrillation and has more than 90% success in eliminating atrial fibrillation. Ablation technologies have played a key role in simplifying this technically demanding procedure and making it available to more patients. A myriad of new lesion sets and approaches were introduced over the last decade which has made the operative treatment of atrial fibrillation less invasive and more confusing.

  View details for DOI 10.1016/j.suc.2009.06.001

  View details for PubMedID 19782848

  View details for PubMedCentralID PMC4332830

• Epicardial Ablation on the Beating Heart: Limited Efficacy of a Novel, Cooled Radiofrequency Ablation Device. Innovations (Philadelphia, Pa.) Lee, A. M., Aziz, A., Sakamoto, S. I., Schuessler, R. B., Damiano, R. J. 2009; 4 (2): 86-92

  Abstract

  OBJECTIVE: To perform a minimally invasive procedure for atrial fibrillation without cardiopulmonary bypass, it is necessary to create transmural lesions on the beating heart. Although bipolar radiofrequency clamps can isolate the pulmonary veins, they have difficulty in performing any other left atrial lesions, particularly those of the traditional Cox-Maze procedure. This study examined the performance of an internally cooled, bipolar radiofrequency device designed for such an application. METHODS: Eleven domestic pigs underwent median sternotomy. Five animals had eight atrial lesions created with the radiofrequency device at times of 20, 30, 40, and 50 seconds. In six other pigs, the device was compared with another technology that has been used clinically for epicardial, beating heart ablation, the Guidant Flex 4 microwave device. The tissue was stained with 2,3,5-triphenyl-tetrazoluim chloride, and the lesions were sectioned at 5-mm intervals. Lesion width, depth, and transmurality were evaluated. RESULTS: The radiofrequency device had a linear dose-response relationship. Lesions were wider and deeper with increasing ablation times. A total of 40%, 45%, 60%, and 67% of lesions were transmural at times of 20, 30, 40, and 50 seconds, respectively. Ninety-one percent of lesions in tissue up to 4-mm thick were transmural after 50 seconds. However, performance in thicker tissue was poor. Lesions created by the device were deeper and more likely to be transmural than the Flex 4. CONCLUSIONS: This internally cooled, bipolar radiofrequency device can reliably create transmural lesions on tissue up to 4-mm thick and performs better than a microwave device.

  View details for DOI 10.1097/IMI.0b013e3181a348a2

  View details for PubMedID 22323899

  View details for PubMedCentralID PMC3273869

• The surgical treatment of atrial fibrillation Surg Clin North Am Lee, A., Melby , S., Damiano, Jr, R. 2009: 1001–1020, x-xi
• Transcriptional and Functional Profiling of Human Embryonic Stem Cell-Derived Cardiomyocytes PLOS ONE Cao, F., Wagner, R. A., Wilson, K. D., Xie, X., Fu, J., Drukker, M., Lee, A., Li, R. A., Gambhir, S. S., Weissman, I. L., Robbins, R. C., Wu, J. C. 2008; 3 (10)

  Abstract

  Human embryonic stem cells (hESCs) can serve as a potentially limitless source of cells that may enable regeneration of diseased tissue and organs. Here we investigate the use of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in promoting recovery from cardiac ischemia reperfusion injury in a mouse model. Using microarrays, we have described the hESC-CM transcriptome within the spectrum of changes that occur between undifferentiated hESCs and fetal heart cells. The hESC-CMs expressed cardiomyocyte genes at levels similar to those found in 20-week fetal heart cells, making this population a good source of potential replacement cells in vivo. Echocardiographic studies showed significant improvement in heart function by 8 weeks after transplantation. Finally, we demonstrate long-term engraftment of hESC-CMs by using molecular imaging to track cellular localization, survival, and proliferation in vivo. Taken together, global gene expression profiling of hESC differentiation enables a systems-based analysis of the biological processes, networks, and genes that drive hESC fate decisions, and studies such as this will serve as the foundation for future clinical applications of stem cell therapies.

  View details for DOI 10.1371/journal.pone.0003474

  View details for Web of Science ID 000265126100005

  View details for PubMedID 18941512

  View details for PubMedCentralID PMC2565131

• Atrial fibrillation propagates through gaps in ablation lines: Implications for ablative treatment of atrial fibrillation HEART RHYTHM Melby, S. J., Lee, A. M., Zierer, A., Kaiser, S. P., Livhits, M. J., Boineau, J. P., Schuessler, R. B., Damiano, R. J. 2008; 5 (9): 1296-1301

  Abstract

  It has been hypothesized that atrial lesions must be transmural to successfully cure atrial fibrillation (AF). However, ablation lines often do not extend completely across the atrial wall.The purpose of this study was to determine the effect of residual gaps on conduction properties of atrial tissue.Canine right atria (n = 13) were isolated, perfused, and mounted on a 250-lead electrode plaque. The atria were divided with a bipolar radiofrequency ablation clamp, leaving a gap that was progressively narrowed. Conduction velocities at varying pacing rates and AF frequencies were measured before and after ablations. AF was induced with an extra stimulus and acetylcholine.Gap widths from 11.2 to 1.1 mm were examined. Conduction velocities through gaps were dependent cycle length (P = .002) and gap size (P <.001). Overall, 253 (97%) of a total of 260 gaps allowed paced propagation; 51 (91%) of 56 gaps 1-3 mm in width permitted paced propagation, as did 202 (99%) of 204 gaps >or=3.0 mm. Similarly, 253 (97%) of a total of 260 gaps allowed propagation of AF. For AF, 51 (93%) of 55 gaps 1-3 mm allowed AF to pass through, as did 202 (99%) of 205 gaps >or=3.0 mm. Gaps as small as 1.1 mm conducted paced and AF impulses.Conduction velocities were slowed through residual gaps. However, propagation of wave fronts during pacing and AF occurred through the majority of residual gaps, down to sizes as small as 1.1 mm. Leaving viable tissue in ablation lines for the treatment of AF could account for failures.

  View details for DOI 10.1016/j.hrthm.2008.06.009

  View details for Web of Science ID 000259281600013

  View details for PubMedID 18774106

  View details for PubMedCentralID PMC2923579

• Efficacy and safety of right and left atrial ablations on the beating heart with irrigated bipolar radiofrequency energy: A long-term animal study JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Melby, S. J., Gaynor, S. L., Lubahn, J. G., Lee, A. M., Rahgozar, P., Caruthers, S. D., Williams, T. A., Schuessler, R. B., Damiano, R. J. 2006; 132 (4): 853-860

  Abstract

  The Cox maze procedure is the most effective surgical treatment for atrial fibrillation; however, its complexity has limited its clinical utility. The purpose of this study was to simplify the procedure by using an irrigated bipolar radiofrequency ablation device on the beating heart without cardiopulmonary bypass.Six domestic pigs underwent median sternotomy. The pulmonary veins were circumferentially ablated. Electrical isolation was confirmed by pacing. Eight lesions were performed epicardially, and three lesions were performed through purse-string sutures with one of the jaws of the device introduced into the right atrium. After 30 days, magnetic resonance imaging was performed to assess atrial function, pulmonary vein anatomy, and coronary artery patency. Cholinergic stimulation and burst pacing were administered to induce atrial fibrillation. Histologic assessment of the heart was performed after the animal was killed.A modified Cox maze procedure was successfully performed with the irrigated bipolar radiofrequency device with no deaths. In every instance, the pulmonary veins were electrically isolated. Cholinergic stimulation with burst pacing failed to produce atrial fibrillation. Imaging studies revealed tricuspid regurgitation without evidence of pulmonary vein stenosis, coronary artery stenosis, or intra-atrial thrombus. Total atrial ejection fraction was 16.9% +/- 7.5%, a significant reduction. Histologically, 99% of the lesions were transmural, and there was no evidence of coronary sinus injury.Lesions on both the right and left atria can be created successfully on the beating heart with irrigated bipolar radiofrequency. The great majority of lesions with this device were transmural. This device should not be used on valvular tissue.

  View details for DOI 10.1016/j.jtcvs.2006.05.048

  View details for Web of Science ID 000240954600016

  View details for PubMedID 17000297

• Microwave ablation for atrial fibrillation: Dose-response curves in the cardioplegia-arrested and beating heart ANNALS OF THORACIC SURGERY Gaynor, S. L., Byrd, G. D., Diodato, M. D., Ishii, Y., Lee, A. M., Prasad, S. M., Gopal, J., Schuessler, R. B., Damiano, R. J. 2006; 81 (1): 72-77

  Abstract

  Microwave ablation has been used to replace the traditional incisions used in the surgical treatment of atrial fibrillation. However, dose-response curves have not been established in surgically relevant models. The purpose of this study was to develop dose-response curves for the Flex 10 (Guidant, Inc) microwave device in both the acute cardioplegia-arrested heart and on the beating heart.Twelve domestic pigs (40 to 45 kg) were subjected to microwave ablation in either the arrested (n = 6) or beating heart (n = 6). The cardioplegia-arrested heart was maintained at 10 degrees to 15 degrees C while six atrial endocardial and seven right ventricular epicardial lesions were created in each animal. On the beating heart, six right atrial and seven ventricular epicardial lesions were created. Ablations were performed for 15, 30, 45, 60, 90, 120, and 150 seconds (65 W, 2.45 GHz). The tissue was stained with 2,3,5-triphenyl-tetrazolium chloride, and sectioned at 5-mm intervals. Lesion depth and width were determined from digital micrographs.Mean atrial wall thickness was 2.8 mm (range, 1 to 8 mm). In the arrested heart, 94% of atrial lesions were transmural at 45 seconds and 100% were transmural at 90 seconds. In the beating heart, only 20% of atrial lesions were transmural despite prolonged ablation times (90 seconds). Ventricular lesion width and depth increased with duration of application, and were similar on the arrested and beating hearts.Microwave ablation produces linear dose-response curves. Transmural lesions can be reliably produced on the arrested heart, but not consistently on the beating heart.

  View details for DOI 10.1016/j.athotacsur.2005.06.062

  View details for Web of Science ID 000234585400009

  View details for PubMedID 16368338

• Dose response curves for microwave ablation in the cardioplegia-arrested porcine heart. heart surgery forum Gaynor, S. L., Byrd, G. D., Diodato, M. D., Ishii, Y., Lee, A. M., Prasad, S. M., Gopal, J., Berube, D., Schuessler, R. B., Damiano, R. J. 2005; 8 (5): E331-6

  Abstract

  Microwave ablation has been used clinically for the surgical treatment of atrial fibrillation, particularly during valve procedures. However, dose- response curves have not been established for this surgical environment. The purpose of this study was to examine dosimetry curves for the Flex 4 and Flex 10 microwave devices in an acute cardioplegia-arrested porcine model.Twelve domestic pigs (40-45 kg) were acutely subjected to Flex 4 (n = 6) and Flex 10 (n = 6) ablations. On a cardioplegically arrested heart maintained at 10-15(o)C, six endocardial atrial and seven epicardial ventricular lesions were created in each animal. Ablations were performed for 15 s, 30 s, 45 s, 60 s, 90 s, 120 s, and 150 s (65 W, 2.45 GHz). The tissue was stained with 2,3,5-triphenyl-tetrazolium chloride and lesions were sectioned at 5 mm intervals. Lesion depth and width were determined from digital photomicrographs of each lesion (resolution +/- .03 mm).Average atrial thickness was 2.88 +/- .4 mm (range 1.0 to 8.0 mm). 94% of ablated atrial sections created by the FLEX 4 (n = 16) and the FLEX 10 (n = 16) were transmural at 45 seconds. 100% of atrial sections were transmural at 90 seconds with the FLEX 10 (n = 14) and at 60 seconds with the Flex 4 device (n = 15). Lesion width and depth increased with duration of application.Both devices were capable of producing transmural lesions on the cardioplegically arrested heart at 65 W. These curves will allow surgeons to ensure transmural ablation by tailoring energy delivery to the specific atrial geometry.

  View details for PubMedID 16099735

• Advances in surgical ablation devices for atrial fibrillation. New Arrhythmia Technologies Melby, S., Lee, A., Damiano, Jr, R. edited by Wang, P., Naccarelli , G., Rosen , M., Estes III , N., Hayes, D., Haines , D. Blackwell Publishing, Malden, Massachusetts. 2005: 233–241