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74 results on '"Jon Kobashigawa"'

1. Paul I. Terasaki, Ph.D: a pioneer in transplant medicine and a dedicated philanthropist

Author

Jon Kobashigawa

Subjects
transplantation, histocompatibility, micro-cytotoxicity, philanthropy, humoral immunity, Specialties of internal medicine, RC581-951
Abstract

In the last five decades, remarkable surgical and medical advances ensued within the field of organ transplantation. These strides were marked by significant breakthroughs in transplant immunology, with Dr. Paul I. Terasaki standing as a true pillar of the field. This article highlights major milestones in Dr. Terasaki's life, his groundbreaking accomplishments in the field of transplant medicine, and his enduring philanthropic contributions to numerous medical and community organizations.

Published
2024
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2. Heart transplantation with super-aged donors older than 65 years

Author

Tasuku Hada, MD, Osamu Seguchi, MD, PhD, Nana Kitahata, CE, Shotaro Komeyama, MD, Hiroki Mochizuki, MD, Takuya Watanabe, MD, PhD, Satoshi Kainuma, MD, PhD, Satsuki Fukushima, MD, PhD, Yasumasa Tsukamoto, MD, PhD, Tomoyuki Fujita, MD, PhD, Jon Kobashigawa, MD, and Norihide Fukushima, MD, PhD

Subjects
heart transplantation, aged donor, donor selection, donor evaluation, cardiac function, Surgery, RD1-811, Specialties of internal medicine, RC581-951
Abstract

Background: This study elucidated the clinical outcomes and serial allograft function of heart transplant (HTx) recipients who received hearts from super-aged donors (SAD) ≥65 years of age. Methods: Adult HTx recipients between 1999 and 2022 were retrospectively reviewed and divided into 2: donor age ≥65 years [SAD group (n = 12)] and donor age

Published
2024
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3. Alterations in the kallikrein-kinin system predict death after heart transplant

Author

Nicholas P. Giangreco, Guillaume Lebreton, Susan Restaino, Maryjane Farr, Emmanuel Zorn, Paolo C. Colombo, Jignesh Patel, Rajesh Kumar Soni, Pascal Leprince, Jon Kobashigawa, Nicholas P. Tatonetti, and Barry M. Fine

Subjects
Medicine, Science
Abstract

Abstract Heart transplantation remains the definitive treatment for end stage heart failure. Because availability is limited, risk stratification of candidates is crucial for optimizing both organ allocations and transplant outcomes. Here we utilize proteomics prior to transplant to identify new biomarkers that predict post-transplant survival in a multi-institutional cohort. Microvesicles were isolated from serum samples and underwent proteomic analysis using mass spectrometry. Monte Carlo cross-validation (MCCV) was used to predict survival after transplant incorporating select recipient pre-transplant clinical characteristics and serum microvesicle proteomic data. We identified six protein markers with prediction performance above AUROC of 0.6, including Prothrombin (F2), anti-plasmin (SERPINF2), Factor IX, carboxypeptidase 2 (CPB2), HGF activator (HGFAC) and low molecular weight kininogen (LK). No clinical characteristics demonstrated an AUROC > 0.6. Putative biological functions and pathways were assessed using gene set enrichment analysis (GSEA). Differential expression analysis identified enriched pathways prior to transplant that were associated with post-transplant survival including activation of platelets and the coagulation pathway prior to transplant. Specifically, upregulation of coagulation cascade components of the kallikrein-kinin system (KKS) and downregulation of kininogen prior to transplant were associated with survival after transplant. Further prospective studies are warranted to determine if alterations in the KKS contributes to overall post-transplant survival.

Published
2022
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4. Correction: Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis.

Author

Antoine Bouquegneau, Charlotte Loheac, Olivier Aubert, Yassine Bouatou, Denis Viglietti, Jean-Philippe Empana, Camilo Ulloa, Mohammad Hassan Murad, Christophe Legendre, Denis Glotz, Annette M Jackson, Adriana Zeevi, Stephan Schaub, Jean-Luc Taupin, Elaine F Reed, John J Friedewald, Dolly B Tyan, Caner Süsal, Ron Shapiro, E Steve Woodle, Luis G Hidalgo, Jacqueline O'Leary, Robert A Montgomery, Jon Kobashigawa, Xavier Jouven, Patricia Jabre, Carmen Lefaucheur, and Alexandre Loupy

Subjects
Medicine
Abstract

[This corrects the article DOI: 10.1371/journal.pmed.1002572.].

Published
2018
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5. Complement-activating donor-specific anti-HLA antibodies and solid organ transplant survival: A systematic review and meta-analysis.

Author

Antoine Bouquegneau, Charlotte Loheac, Olivier Aubert, Yassine Bouatou, Denis Viglietti, Jean-Philippe Empana, Camilo Ulloa, Mohammad Hassan Murad, Christophe Legendre, Denis Glotz, Annette M Jackson, Adriana Zeevi, Stephan Schaub, Jean-Luc Taupin, Elaine F Reed, John J Friedewald, Dolly B Tyan, Caner Süsal, Ron Shapiro, E Steve Woodle, Luis G Hidalgo, Jacqueline O'Leary, Robert A Montgomery, Jon Kobashigawa, Xavier Jouven, Patricia Jabre, Carmen Lefaucheur, and Alexandre Loupy

Subjects
Medicine
Abstract

BACKGROUND:Anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) are recognized as a major barrier to patients' access to organ transplantation and the major cause of graft failure. The capacity of circulating anti-HLA DSAs to activate complement has been suggested as a potential biomarker for optimizing graft allocation and improving the rate of successful transplantations. METHODS AND FINDINGS:To address the clinical relevance of complement-activating anti-HLA DSAs across all solid organ transplant patients, we performed a meta-analysis of their association with transplant outcome through a systematic review, from inception to January 31, 2018. The primary outcome was allograft loss, and the secondary outcome was allograft rejection. A comprehensive search strategy was conducted through several databases (Medline, Embase, Cochrane, and Scopus). A total of 5,861 eligible citations were identified. A total of 37 studies were included in the meta-analysis. Studies reported on 7,936 patients, including kidney (n = 5,991), liver (n = 1,459), heart (n = 370), and lung recipients (n = 116). Solid organ transplant recipients with circulating complement-activating anti-HLA DSAs experienced an increased risk of allograft loss (pooled HR 3.09; 95% CI 2.55-3.74, P = 0.001; I2 = 29.3%), and allograft rejection (pooled HR 3.75; 95% CI: 2.05-6.87, P = 0.001; I2 = 69.8%) compared to patients without complement-activating anti-HLA DSAs. The association between circulating complement-activating anti-HLA DSAs and allograft failure was consistent across all subgroups and sensitivity analyses. Limitations of the study are the observational and retrospective design of almost all included studies, the higher proportion of kidney recipients compared to other solid organ transplant recipients, and the inclusion of fewer studies investigating allograft rejection. CONCLUSIONS:In this study, we found that circulating complement-activating anti-HLA DSAs had a significant deleterious impact on solid organ transplant survival and risk of rejection. The detection of complement-activating anti-HLA DSAs may add value at an individual patient level for noninvasive biomarker-guided risk stratification. TRIAL REGISTRATION:National Clinical Trial protocol ID: NCT03438058.

Published
2018
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6. The Natural History of Biopsy-Negative Rejection after Heart Transplantation

Author

Zhaoyi Tang, Jon Kobashigawa, Matthew Rafiei, Lily Kagan Stern, and Michele Hamilton

Subjects
Surgery, RD1-811
Abstract

Purpose. The most recent International Society for Heart and Lung Transplantation (ISHLT) biopsy scale classifies cellular and antibody-mediated rejections. However, there are cases with acute decline in left ventricular ejection fraction (LVEF ≤ 45%) but no evidence of rejection on biopsy. Characteristics and treatment response of this biopsy negative rejection (BNR) have yet to be elucidated. Methods. Between 2002 and 2012, we found 12 cases of BNR in 11 heart transplant patients as previously defined. One of the 11 patients was treated a second time for BNR. Characteristics and response to treatment were noted. Results. 12 cases (of 11 patients) were reviewed and 11 occurred during the first year after transplant. 8 cases without heart failure symptoms were treated with an oral corticosteroids bolus and taper or intravenous immunoglobulin. Four cases with heart failure symptoms were treated with thymoglobulin, intravenous immunoglobulin, and intravenous methylprednisolone followed by an oral corticosteroids bolus and taper. Overall, 7 cases resulted in return to normal left ventricular function within a mean of 14 ± 10 days from the initial biopsy. Conclusion. BNR includes cardiac dysfunction and can be a severe form of rejection. Characteristics of these cases of rejection are described with most cases responding to appropriate therapy.

Published
2013
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9. Experience With SynCardia Total Artificial Heart as a Bridge to Transplantation in 100 Patients

Author

Jad Malas, Qiudong Chen, Akbarshakh Akhmerov, Louis Philippe Tremblay, Natalia Egorova, Aasha Krishnan, Jaime Moriguchi, Jon Kobashigawa, Lawrence Czer, Robert Cole, Dominic Emerson, Joanna Chikwe, Francisco Arabia, and Fardad Esmailian

Subjects
Pulmonary and Respiratory Medicine, Surgery, Cardiology and Cardiovascular Medicine
Abstract

The SynCardia total artificial heart (TAH-t) is an effective bridge to transplantation for patients with severe biventricular failure. However, granular single-center data from high volume centers are lacking. We report our experience with the first 100 TAH-t recipients.A prospective institutional database was used to identify 100 patients who underwent 101 TAH-t implantations between 2012 and 2022. Patients were stratified and compared according to Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 versus2. Median follow-up on device support was 94 days (IQR: 33-276 days), while median post-transplantation follow-up was 4.6 years (IQR: 2.1-6.0 years).Overall, 61 patients (61%) were successfully bridged to transplantation while 39 (39%) died on TAH-t support. Successful bridge rates between INTERMACS profile 1 and INTERMACS profile2 patients were similar (55.6%, 95% CI 40.4-68.3% versus 67.4%, 95% CI 50.5-79.6%, respectively, p=0.50). The most common adverse events (rates per 100 patient-months) on TAH-t support included infection (15.8), ischemic stroke (4.6), reoperation for mediastinal bleeding (3.5), and gastrointestinal bleeding requiring intervention (4.3). The most common cause of death on TAH-t support was multisystem organ failure (n=20, 52.6%). Post-transplantation thirty-day survival was 96.7%, while survival at 6 months, 1 year, and 5 years post-transplantation were 95.1% (95% CI 85.4-98.4%), 86.6% (95% CI 74.9-93.0%), and 77.5% (95% CI 64.2-86.3%), respectively.Acceptable outcomes can be achieved in the highest acuity patients utilizing the TAH-t as a bridge to heart transplantation.

Published
2023
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10. Addressing sex-based disparities in solid organ transplantation in the United States – a conference report

Author

Deirdre Sawinski, Jennifer C. Lai, Sean Pinney, Alice L. Gray, Annette M. Jackson, Darren Stewart, Deborah Jo Levine, Jayme E. Locke, James J. Pomposelli, Matthew G. Hartwig, Shelley A. Hall, Darshana M. Dadhania, Rebecca Cogswell, Richard V. Perez, Jesse D. Schold, Nicole A. Turgeon, Jon Kobashigawa, Jasleen Kukreja, John C. Magee, John Friedewald, John S. Gill, Gabriel Loor, Julie K. Heimbach, Elizabeth C. Verna, Mary Norine Walsh, Norah Terrault, Guiliano Testa, Joshua M. Diamond, Peter P. Reese, Kimberly Brown, Susan Orloff, Maryjane A. Farr, Kim M. Olthoff, Mark Siegler, Nancy Ascher, Sandy Feng, Bruce Kaplan, and Elizabeth Pomfret

Subjects
Transplantation, Immunology and Allergy, Pharmacology (medical)
Published
2023
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11. Donor heart selection: Evidence-based guidelines for providers

Author

Hannah Copeland, Ivan Knezevic, David A. Baran, Vivek Rao, Michael Pham, Finn Gustafsson, Sean Pinney, Brian Lima, Marco Masetti, Agnieszka Ciarka, Navin Rajagopalan, Adriana Torres, Eileen Hsich, Jignesh K. Patel, Livia Adams Goldraich, Monica Colvin, Javier Segovia, Heather Ross, Mahazarin Ginwalla, Babak Sharif-Kashani, MaryJane A. Farr, Luciano Potena, Jon Kobashigawa, Maria G. Crespo-Leiro, Natasha Altman, Florian Wagner, Jennifer Cook, Valentina Stosor, Paolo A. Grossi, Kiran Khush, Tahir Yagdi, Susan Restaino, Steven Tsui, Daniel Absi, George Sokos, Andreas Zuckermann, Brian Wayda, Joost Felius, and Shelley A. Hall

Subjects
Pulmonary and Respiratory Medicine, Brain Death, Transplantation, Consensus, adult, practice guideline, article, selection, donor selection, brain death, donor heart, donor risk factors, heart transplant, heart transplantation, Tissue Donors, risk factor, Humans, Surgery, heart graft, human, Cardiology and Cardiovascular Medicine, donor
Abstract

The proposed donor heart selection guidelines provide evidence-based and expert-consensus recommendations for the selection of donor hearts following brain death. These recommendations were compiled by an international panel of experts based on an extensive literature review. © 2022 International Society for Heart and Lung Transplantation

Published
2023
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14. Extracorporeal membrane oxygenation as a bridge to durable mechanical circulatory support or heart transplantation

Author

Breanna Hansen, Tahli Singer Englar, Robert Cole, Pedro Catarino, David Chang, Lawrence Czer, Dominic Emerson, Dael Geft, Jon Kobashigawa, Dominick Megna, Danny Ramzy, Jaime Moriguchi, Fardad Esmailian, and Michelle Kittleson

Subjects
Adult, Heart Failure, Shock, Cardiogenic, Biomedical Engineering, Medicine (miscellaneous), Bioengineering, General Medicine, Biomaterials, Extracorporeal Membrane Oxygenation, Treatment Outcome, Heart Transplantation, Humans, Heart-Assist Devices, Retrospective Studies
Abstract

Background: Patients with cardiogenic shock may require extracorporeal membrane oxygenation (ECMO) prior to durable mechanical circulatory support (dMCS) or heart transplantation (HTx). Methods: We investigated the clinical characteristics and outcomes of adult patients with ECMO support as bridge to dMCS or HTx between 1/1/13 and 12/31/20. Results: Of 57 patients who underwent bridging ECMO, 41 (72%) received dMCS (approximately half with biventricular support) and 16 (28%) underwent HTx, 13 (81%) after the 2018 UNOS allocation system change. ECMO → HTx patients had shorter ventilatory time (3.5 vs 7.5 days; p = 0.018), ICU stay (6 vs 18 days; p = 0.001), and less need for inpatient rehabilitation (18.8% vs 57.5%; p = 0.016). The 1-year survival post HTx was 81.3% in the ECMO → HTx group and 86.4% in the ECMO → dMCS group ( p = 0.11). For those patients in the ECMO → dMCS group who did not undergo HTx, 1-year survival was significantly lower, 31.6% ( p = 0.001). Conclusion: Patients on ECMO who undergo HTx, with or without dMCS bridge, have acceptable post-HTx survival. These findings suggest that HTx from ECMO is a viable option for carefully selected patients deemed acceptable to proceed with definitive advanced therapies, especially in the era of the new UNOS allocation system.

Published
2022
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15. Long-term preservation of functional capacity and quality of life in advanced heart failure patients with bridge to transplant therapy: A report from Japanese nationwide multicenter registry

Author

Takuma, Sato, Yuta, Kobayashi, Toshiyuki, Nagai, Takeshi, Nakatani, Jon, Kobashigawa, Yoshikatsu, Saiki, Minoru, Ono, Satoru, Wakasa, and Toshihisa, Anzai

Subjects
Heart Failure, Treatment Outcome, Japan, Quality of Life, Heart Transplantation, Humans, Heart-Assist Devices, Registries, Cardiology and Cardiovascular Medicine, United States, Retrospective Studies
Abstract

Under the revised heart allocation system in the United States, bridge to transplant (BTT) patients with left ventricular assist device (LVAD) have a longer waitlist period, as they are now lowly prioritized. However, little is known regarding the long-term trajectory of functional capacity (FC) and health-related quality of life (HR-QOL) among BTT-LVAD patients.We retrospectively analyzed 442 consecutive patients with BTT-LVAD between April 2013 and May 2019 from a Japanese nationwide registry. FC (New York Heart Association [NYHA] functional class, peak oxygen uptake [VODuring the follow-up period of 30 months (IQR 18-42 months), 100 (22.6%) patients underwent transplantation, 37 (8.3%) died, and 14 (3.1%) underwent explantation for recovery. Mean peak VOBTT patients showed long-term preservation of FC and HR-QOL, suggesting that BTT remains an option despite the long waiting time to HTx.

Published
2022
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16. Temporary Left Ventricular Support Device as a Bridge to Heart-Liver or Heart-Kidney Transplant: Pushing the Boundaries of Temporary Support

Author

Amy, Roach, Dominic, Emerson, Dominick, Megna, Robert, Cole, Pedro, Catarino, Reza, Salabat, Danny, Ramzy, Jamie, Moriguchi, Jon, Kobashigawa, Alfredo, Trento, Joanna, Chikwe, and Fardad, Esmailian

Subjects
Biomaterials, Biomedical Engineering, Biophysics, Bioengineering, General Medicine
Abstract

In patients with severe cardiogenic shock, temporary mechanical circulatory support has become a viable strategy to bridge patients to heart transplantation. However, end-stage heart failure is often associated with progressive organ dysfunction of the liver or kidney. This can require a dual organ transplant for definitive management (combined heart-liver [HL] or heart-kidney [HK] transplantation). We evaluated temporary mechanical support to bridge patients to HL or HK transplant at a single, high-volume center. All patients who underwent Impella 5.0 placement from January 2014 to October 2018 were identified. From this dataset, patients who underwent placement as a bridge to dual organ transplant were selected, as were those who underwent Impella as a bridge to isolated heart transplant. Over the 5 years of evaluation, 104 patients underwent Impella 5.0 placement. Of these, 14.3% (n = 15) were identified as potential dual organ recipients (11 HK, 4 HL). In total, 80% (12/15) successfully underwent dual organ transplant (8 HK, 4 HL), with a 1-year survival of 100% in both transplanted groups. Among patients undergoing Impella 5.0 placement as a bridge to isolated heart transplant (n = 33), 78.8% (26) were successfully bridged, and 1-year survival was 92% after transplantation. Impella 5.0 is a viable bridge to dual organ transplantation and should be considered as a management strategy in these complex patients at experienced institutions.

Published
2022
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18. The evolving use of biomarkers in heart transplantation: consensus of an expert panel

Author

Jon Kobashigawa, Shelley Hall, Palak Shah, Barry Fine, Phil Halloran, Annette M. Jackson, Kiran K. Khush, Kenneth B. Margulies, Maryam Mojarrad Sani, Jignesh K. Patel, Nikhil Patel, Eliot Peyster, Shelly Hall, Sean Agbor-Enoh, Robert Bray, Martin Cadeiras, Patty Chang, Sharon Chih, Howie Eisen, Maryjane Farr, Kambiz Ghafourian, Annette M Jackson, Andrew Kao, Kiran K Khush, Anant Madabhushi, Kenneth B Margulies, Jignesh K Patel, Anil Parwani, Sean Pinney, Kelley Schlendorf, Keyur Shah, Josef Stehlik, Anat Tambur, and Adriana Zeevi

Subjects
Transplantation, Immunology and Allergy, Pharmacology (medical)
Published
2023
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20. Change in First-year Intravascular Ultrasound Results Predicts Adverse Events in Heart Transplant Recipients: Implications for Clinical Trial Endpoints

Author

Osamu Seguchi, Babak Azarbal, James Mirocha, Jong-Chan Youn, Elizabeth Passano, Jignesh Patel, and Jon Kobashigawa

Subjects
Transplantation
Abstract

Heart transplantation (HTx) is an established therapeutic option for patients with advanced heart failure who are refractory to conventional guideline-directed treatments. This study aimed to reassess whether intravascular ultrasound variables could predict adverse events after HTx in the modern era.One hundred primary HTx recipients with available serial intravascular ultrasound examination results of the left anterior descending artery 4-8 wk and 1 y after HTx were enrolled, with an average follow-up duration of 5.7 y. The primary endpoint was a composite of all-cause death, nonfatal major adverse cardiac events, and angiographic cardiac allograft vasculopathy.Forty-three patients developed primary endpoints. The baseline maximal intimal thickness was independently associated with the primary endpoint (hazard ratio, 8.24; 95% confidential interval [CI], 3.21-21.21; P 0.001), and the optimal cutoff value was 0.64 mm. A change in the plaque atheroma volume in a proximal 20-mm segment from the left anterior descending artery bifurcation1.05 mm 3 /mm (hazard ratio, 2.75; 95% CI, 1.28-5.89; P = 0.009) and a change in the first-year maximal intimal thickness0.27 mm (hazard ratio, 2.63; 95% CI, 1.05-6.56; P = 0.04) were independent predictors of the primary endpoint 1 y after intravascular ultrasonography.The aforementioned important clinical implications of intravascular ultrasound parameters are useful predictors of outcomes, which may be considered endpoints in modern clinical HTx trials.

Published
2022

21. Clinical Prediction Model for Antibody-Mediated Rejection: A Strategy to Minimize Surveillance Endomyocardial Biopsies After Heart Transplantation

Author

Guillaume Coutance, Evan Kransdorf, Olivier Aubert, Guillaume Bonnet, Daniel Yoo, Philippe Rouvier, Jean-Paul Duong Van Huyen, Patrick Bruneval, Jean-Luc Taupin, Pascal Leprince, Shaida Varnous, Jon Kobashigawa, Xavier Jouven, Jignesh Patel, and Alexandre Loupy

Subjects
Graft Rejection, Heart Failure, Models, Statistical, Myocardium, Biopsy, Humans, Heart Transplantation, Prognosis, Cardiology and Cardiovascular Medicine, Antibodies, Retrospective Studies
Abstract

Background: In heart transplantation, antibody-mediated rejection (AMR) is a major contributor to patient morbidity and mortality. Multiple routine endomyocardial biopsies (EMB) remain the gold standard to detect AMR, but this invasive procedure suffers from many limitations. We aimed to develop and validate an AMR risk model to improve individual risk stratification of AMR. Methods: Heart recipients from 2 referral transplant centers, Cedars-Sinai (US) and Pitié-Salpêtrière (France), were included from 2012 to 2019. Database included detailed clinical, immunologic, imaging, and histological parameters. The US cohort was randomly distributed in a derivation (2/3) and in a test set (1/3). The primary end point was biopsy-proven AMR. A mixed effect logistic regression model with a random intercept was applied to identify variables independently associated with AMR. Simulation analyzes were performed. Results: The US and French cohorts comprised a total of 1341 patients, representing 12 864 EMB. Overall, 490 AMR episodes were diagnosed (3.8% of EMB). Among the 26 potential determinants of AMR, 5 variables showed independent association: time post-transplant ( P P =0.001), circulating donor-specific anti–human leukocyte antigen antibody ( P =0.001), graft dysfunction ( P =0.004), and prior history of definite AMR ( P Conclusions: Our results support the use of the AMR risk model as a clinical decision tool to minimize the number of routine EMB after heart transplantation.

Published
2022
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22. Initial Invasive or Conservative Strategy for Stable Coronary Disease

Author

Maron D. J., Hochman J. S., Reynolds H. R., Bangalore S., O'Brien S. M., Boden W. E., Chaitman B. R., Senior R., Lopez-Sendon J., Alexander K. P., Lopes R. D., Shaw L. J., Berger J. S., Newman J. D., Sidhu M. S., Goodman S. G., Ruzyllo W., Gosselin G., Maggioni A. P., White H. D., Bhargava B., Min J. K., John Mancini G. B., Berman D. S., Picard M. H., Kwong R. Y., Ali Z. A., Mark D. B., Spertus J. A., Krishnan M. N., Elghamaz A., Moorthy N., Hueb W. A., Demkow M., Mavromatis K., Bockeria O., Peteiro J., Miller T. D., Szwed H., Doerr R., Keltai M., Selvanayagam J. B., Gabriel Steg P., Held C., Kohsaka S., Mavromichalis S., Kirby R., Jeffries N. O., Harrell F. E., Rockhold F. W., Broderick S., Bruce Ferguson T., Williams D. O., Harrington R. A., Stone G. W., Rosenberg Y, ISCHEMIA Research Group: Joseph Ricci, A Tello Montoliu, A I Robero Aniorte, Abbey Mulder, Abhay A Laddu, Abhinav Goyal, Abhishek Dubey, Abhishek Goyal, Abigail Knighton, Abraham Oomman, Adam J Jaskowiak, Adam Kolodziej, Adam Witkowski, Adnan Hameed, Adriana Anesini, Afshan Hussain, Agne Juceviciene, Agne Urboniene, Agnes Jakal, Agnieszka Szramowska, Ahmad Khairuddin, Ahmed Abdel-Latif, Ahmed Adel, Ahmed Aljzeeri, Ahmed Kamal, Ahmed Talaat, Aimee Mann, Aira Contreras, Ajit Kumar, V K Kumar, Akemi Furukawa, Akshay Bagai, Akvile Smigelskaite, Alain Furber, Alain Rheault, Alaine Melanie Loehr, Alan Rosen, Albert Varga, Albertina Qelaj, Alberto Barioli, Aldo Russo, Alec Moorman, Alejandro Gisbert, Aleksandra Fratczak, Aleksandras Laucevicius, Alena Kuleshova, Alessandro Sionis, Alexander A Sirker, Alexander M Chernyavskiy, Alexandra Craft, Alexandra Vazquez, Alexandre Ciappina Hueb, Alexandre S Colafranseschi, Alexandre Schaan de Quadros, Alexandre Tognon, Ali Alghamdi, Alice Manica Muller, Aline Nogueira Rabaça, Aline Peixoto Deiro, Alison Hallam, Allegra Stone, Allison Schley, Almudena Castro, Alvaro Rabelo Ales, Amanda Germann, Amanda O'Malley, Amar Uxa, Amarachi Ojajuni, Amarino C Oliveira Jr, Amber B Hull, Ambuj Roy, Amer Zarka, Amir Janmohamed, Ammani Brown, Ammy Malinay, Amparo Martinez Monzonis, Amy J Richards, Amy Iskandrian, Amy Ollinger, Ana D Djordjevic-Dikic, Ana Fernández Martínez, Ana Gomes Almeida, Ana Paula Batista, Ana Rita Francisco, Ana S Mladenovic, Ana Santana, Anam Siddiqui, Anastasia M Kuzmina-Krutetskaya, Andras Vertes, Andre S Sousa, Andre Gabriel, André Schmidt, Andrea M Lundeen, Andrea Bartykowszki, Andrea Lorimer, Andrea Mortara, Andrea Pascual, Andreia Coelho, Andreia Rocha, Andrés García-Rincón, Andrew G Howarth, Andrew J Moriarty, Andrew Docherty, Andrew Starovoytov, Andrew Zurick, Andrzej Łabyk, Andrzej Swiatkowski, Andy Lam, Anelise Kawakami, Angela Hoye, Angela Kim, Angelique Smit, Angelo Nobre, Anil V Shah, Anja Ljubez, Anjali Anand, Ankush Sachdeva, Ann Greenberg, Ann Luyten, Ann Ostrander, Anna Di Donato, Anna Cichocka-Radwan, Anna Fojt, Anna Plachcinska, Anna Proietti, Anna Teresinska, Anne Marie Webb, Anne Cartwright, Anne Heath, Anne Mackin, Anong Amaritakomol, Anong Chaiyasri, Anoop Chauhan, Anoop Mathew, Anthony Gemignani, Anto Luigi Andres, Antonia Vega, Antonietta Hansen, Antonino Ginel Iglesias, Antonio Carlos Carvalho, Antonio Di Chiara, Antonio Serra Peñaranda, Antonio Carvalho, Antonio Colombo, Antonio Fiarresga, Anupama Rao, Aquiles Valdespino-Estrada, Araceli Boan, Areef Ishani, Ariel Diaz, Arijit Ghosh, Arintaya Prommintikul, Arline Roberts, Arnold H Seto, Arnold P Good, Arshed Quyyumi, Arthur J Labovitz, Arthur Kerner, Arturo S Campos-Santaolalla, Arunima Misra, Ashok Mukherjee, Ashok Seth, Ashraf Seedhom, Asim N Cheema, Asker Ahmed, Atul Mathur, Atul Verma, Audrey W Leong, Axel Åkerblom, Axelle Fuentes, Aynun Naher, Badhma Valaiyapathi, Baljeet Kaur, Bandula Guruge, Barbara Brzezińska, Barbara Nardi, Bartosz Czarniak, Bebek Singh, Begoña Igual, Bela Merkely, Belen Cid Alvarez, Benjamin J Spooner, Benjamin J W Chow, Benjamin Cheong, Benoy N Shah, Bernard de Bruyne, Bernardas Valecka, Bernhard Jäger, Beth A Archer, Beth Abramson, Beth Jorgenson, Bethany Harvey, Betsy O'Neal, Bev Atkinson, Bev Bozek, Bevin Lang, Bijulal Sasidharan, Bin Yang, Bin Zhang, Binoy Mannekkattukudy Kurian, Bjoern Goebel, Bob Hu, Bogdan A Popescu, Bogdan Crnokrak, Bolin Zhu, Bonnie J Kirby, Brandi D Zimbelman, Brandy Starks, Branko D Beleslin, Brenda Hart, Brian P Shapiro, Brian McCandless, Brianna Wisniewski, Brigham R Smith, Brooks Mirrer, Bruce McManus, Bruce Rutkin, Bruna Edilena Paulino, Bruna Maria Ascoli, Bryn Smith, Byron J Allen, C Michael Gibson, C Noel Bairey Merz, Calin Pop, Cameron Hague, Camila Thais de Ormundo, Candace Gopaul, Candice P Edillo, Carísi A Polanczyk, Carita Krannila, Carla Vicente, Carl-Éric Gagné, Carlo Briguori, Carlos Peña Gil, Carlos Alvarez, Carly Ohmart, Carmen C Beladan, Carmen Ginghina, Carol M Kartje, Caroline Alsweiler, Caroline Brown, Caroline Callison, Caroline Pinheiro, Caroline Rodgers, Caroline Spindler, Carolyn Corbett, Carrie Drum, Casey Riedberger, Catherine Bone, Catherine Fleming, Catherine Gordon, Catherine Jahrsdorfer, Catherine Lemay, Catherine Weick, Cathrine Patten, Cecilia Goletto, Cezary Kepka, Chandini Suvarna, Chang Xu, Chantale Mercure, Charle A Viljoen, Charlene Wiyarand, Charles Jia-Yin Hou, Charles Y Lui, Charles Cannan, Charles Cornet, Charlotte Pirro, Chataroon Rimsukcharoenchai, Chen Wang, Cheng-Ting Tsai, Chen-Yen Chien, Cheryl A Allardyce, Chester M Hedgepeth, Chetan Patel, Chiara Attanasio, Chih-Hsuan Yen, Chi-Ming Chow, Ching Min Er, Ching-Ching Ong, Cholenahally Nanjappa Manjunath, Chris Beck, Chris Buller, Christel Vassaliere, Christian Hamm, Christiano Caldeira, Christie Ballantyne, Christina Björklund, Christine R Hinton, Christine Bergeron, Christine Masson, Christine Roraff, Christine 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Arcand, Linda Davidson-Ray, Linda Schwarz, Lindsey N Sikora, Lingping Chi, Lino Patricio, Liping Zhang, Lisa Chaytor, Lisa Hatch, Lisa McCloy, Lisa Wong, Liselotte Persson, Lixin Jiang, Liz Low, Ljiljana Pupic, Loïc Bière, Lorenzo Monti, Lori Christensen, Lori Pritchard, Loriane Black, Lori-Ann Desimone, Lori-Ann Larmand, Lorraine McGregor, Louise Morby, Louise Thomson, Luc Harvey, Luciana de Pádua Baptista, Lucilla Garcia, Ludivine Eliahou, Ludmila Helmer, Luis F Smidt, Luis Bernanrdes, Luis Guzman, Luiz A Carvalho, Luyang Xiong, Lynette L Teo, Lynn M Neeson, Lynne Winstanley, M Barbara Srichai-Parsia, M Quintana Giner, M Sowjanya Reddy, M Valdés Chávarri, M Grazia Rossi, Maarten Simoons, Maayan Konigstein, Maciej Lesiak, Maciej Olsowka, Mafalda Selas, Magalie Corfias, Magdalena Madero Rovalo, Magdalena Łanocha, Magdalena Miller, Magdalena Misztal-Teodorczyk, Magdalena Rantinella, Magdy Abdelhamid, Magnolia Jimenez, Mahboob Alam, Mahevamma Mylarappa, Mahfouz El Shahawy, Mahmoud Mohamed, Mahmud Al-Bustami, Majo X Joseph, Malgorzata Frach, Małgorzta Celińska-Spodar, Malte Helm, Manas Chacko, Mandy Murphy, Manitha Vinod, Manjula Rani, Manu Dhawan, Manuela Mombelli, Marcel Weber, Marcello Galvani, Marcelo Jamus Rodrigues, Marcia F Dubin, Marcia F Werner Bayer, Marcin Szkopiak, Marco Antonio Monsalve, Marco Bizzaro Santos, Marco Magnoni, Marco Marini, Marco Sicuro, Marco Zenati, Marcos Valério Coimbra Resende, Marek Roik, Margalit Bentzvi, Margaret Gilsenan, Margaret Iraola, Margot C Quinn, Maria A Alfonso, Maria Antonieta Pereira Moraes, María Dolores Martínez-Ruíz, María Fernanda Canales, Maria Inês Caetano, Maria P Corral, Maria Pérez García, Maria Victoria Actis, Maria Aguirre, Maria Andreasson, Maria Aprile, Maria Colton, Maria Eugenia Martin, Maria Lasala, Maria Lorenzo, Maria Posada, Maria Shier, Maria Thottam, Mariana V Furtado, Mariana Yumi Okada, Marianna D A Dracoulakis, Marianne De Andrade, Mariano Rubio, Marie Essermark, Marielle Scherrer-Crosbie, Marija T Petrovic, Marija Zdravkovic, Marilyn Black, Marina Garcia, Mario J Garcia, Mariola Szulik, Marisa Orgera, Mark A de Belder, Mark Harbinson, Mark Hyun, Mark Peterson, Mark Xavier, Marlowe Mosley, Marta Capinha, Marta Marcinkiewicz-Siemion, Marta Swiderek, Martha Meyer, Martina Ceseri, Martina Tricoli, Marvin Kronenberg, Mary Williams, Mary Ann Champagne, Mary Colleen Rogge, Mary R Soltau, Mary Streif, Massimo Villella, Massoud Leesar, Matei Claudia, Mateusz Solecki, Matías Nicolás Mungo, Matthew Wall Jr, Matthew Budoff, Matthew Jezior, Matthew Luckie, Matthias Friedrich, Mauren P Haeffner, Maximilian Tscharre, Max-Paul Winter, Mayana Almeida, Mayil S Krishnam, Mayuri Patel, Meenakshi Mishra, Megan Manocchia, Meghana Kakade, Melanie J Munro, Melissa D Chaplin, Melissa LeFevre, Mervyn Andiapen, Michael A Gibson, Michael B Rubens, Michael C Turner, Michael D Shapiro, Michael W Lee, Michael Berlowitz, Michael Davidson, Michael Mack, Michael McDaniel, Michael Mumma, Michal Wlodarczyk, Michel G Khouri, Michel S Slama, Michele Rawlins, Michelle M Bonner, Michelle M Seib, Michelle Chang, Michelle Crowder, Michelle Dixon, Michelle Mayon, Michelle McEvoy, Michelle Yee, Miguel M Fernandes, Miguel Nobre Menezes, Miguel Souto Bayarri, Miguel Barrero, Mikhail T Torosoff, Milan R Dobric, Milan Dobric, Milica Nikola Dekleva, Milind Avdhoot Gadkari, Millie Gomez, Min Tun Kyaw, Miriam Brooks, Miroslav Stevo Martinovic, Mitchel B Lustre, Mohammad Tariq Vakani, Mohammad El-Hajjar, Mohammed Al-Amoodi, Mohammed Hussain, Mohammed Saleem, Moisés Blanco-Calvo, Moisés Jiménez-Santos, Mona Bhatia, Monica Rosca, Monika Laukyte, Montserrat Gracida Blanca, Montserrat Vila Perales, Mouaz H Al-Mallah, Moysés de Oliveira Filho, Mpiko Ntsekhe, Muhamed Saric, Mulei Chen, Myriam Brousseau, Myrthes Emy Takiuti, Nada Cemerlic-Adjic, Nadia Asif, Nadia Gakou, Nafisa Hussain, Nana O Katamadze, Nancy L Clapp, Nancy Aedy, Nandita Nataraj, Nanette K Wenger, Naomi Uchida, Nasrul Ismail, Natalia S Oliveira, Natalia de Carvalho Maffei, Natalie Spitzer, Natasha C Putnam, Naved Aslam, Neamat Mowafy, Neeraj Pandit, Neeraj Parakh, Nevena Garcevic, Ngaire Meadows, Nhi N Tran, Nicholas Danchin, Nicki Lakeman, Nicola Johnston, Nicolas W Shammas, Nicole Saint Vrestil, Nicole Deming, Nier Zhong, Niket Patel, Nikola N Boskovic, Nikolaos Karogiannis, Nikos Werner, Nina Johnston, Ning Zhang, Ning Zhou, Niree Hindoyan, Nirmal Kumar, Nitika Chadha, Nitish Naik, Nodira Aripova, Noloyiso Mtana, Nona A Eskelson, Noor Syamira Mokhtar, Noppon Taksaudom, Nor Asiah Basri, Nora Marchelletta, Norma Hogg, Nungshi Jungla, Nuno Ferreira, Oksana A Lubyanaya, Olga B Nikolaeva, Olga Cañavate, Olga Sobrino, Olga Walesiak, Olga Walter, Olga Zdończyk, Olivia J Lim, Olivia Anaya, Olivia Mancilla, Olivier Dubourg, Olugbenga Bello, Omar Almousalli, Omar Thompson, Oni Olurinde, Or Harel, Osama Raheem, Oscar Méndiz, Óscar Prada-Delgado, Oz Shapira, P Christian Schulze, Pachara Panpunuan, Pal Maurovich-Horvat, Pallav Garg, Paloma Moraga, Pam Singh, Pamela Julian, Pamela Ouyang, Pamela Sigel, Pamela Woodard, Panpan Zhou, Paola Emanuela Poggio, Paola Smanio, Paolo Calabro, Paramjit Jeetley, Pascal Goube, Patricia K Nguyen, Patricia Alarie, Patricia Arakelian, Patricia Arsenault, Patricia Blaise, Patricia Brito, Patricia Cowper, Patricia Endsley, Patricia Mieses, Patrick B Alexander, Patrick Donnelly, Patrick Wilmot, Patrycja Lebioda, Paul C Gordon, Paul Der Mesropian, Paul Galiwango, Paul Hauptman, Paul Kennedy, Paula Beardsley, Paula García-González, Paulo Cury Rezende, Paulo Ricardo Caramori, Pavel S Kozlov, Pedro Canas Silva, Pedro Gabriel Melo Barros E Silva, Pedro Píccaro de Oliveira, Pedro Carvalho, Pedro Modas, Pedro Rio, Peeyush Jain, Peiyu He, Peter A McCullough, Peter H Stone, Peter M Pollak, Peter Douglass, Peter Henriksen, Peter OKane, Peter Ong, Philip Jones, Philip Rogal, Philippe Généreux, Philippe Menasche, Philippe Rheault, Phoebe Goold, Pierre Gervais, Pierre Michaud, Pilar Calvillo, Ping Chai, Piotr Jakubowski, Piotr Pruszczyk, Piotr Slomka, Piyamitr Sritara, Poay-Huan Loh, Poonam Sonawane, Pouneh Samadi, Pragnesh P Parikh, Prakash Deedwania, Pranav M Patel, Praneeth Polamuri, Pratiksha Sharma, Precilia Vasquez, Preeti Kamath, Prince Thomas, Priyadarshani Arambam, Puja K Mehta, Purvez Grant, Pushpa Naik, Qi Zhong, Qian Zhao, Qiang Zhou, Qianqian Yuan, Qin Yu, Qingxian Li, Qiulan Xie, Qiutang Zeng, R J Vindhya, R James Gerlach, Rachel King, Rada Vučić, Radmila Lyubarova, Radoslaw Pracon, Raewyn Fisher, Rafael Beyar, Rafael Diaz, Rafael Selgas, Raffaele Bugiardini, Raffaele Fanelli, Raisa Kavalakkat, V S Rajalekshmi, Rajat S Barua, Rajeev Menon, Rajesh Gopalan Nair, Rajesh Francis, Rajiv Narang, Rakesh Yadav, Ralph Alan Huston, T Ramakrishnan, Ramesh de Silva, Rami El Mahmoud, Ramiro Carvalho, Ramon de Jesús-Pérez, Ramona Stevens, Ran Leng, Ranjan Kachru, Ranjit Kumar Nath, Raquel Sanchez, Raven R Dwyer, Raven Lee, Ray Wyman, Raymond C Wong, Raymond W Little, Raymundo Ocaranza Sanchez, Rebecca J Wimmer, Rebecca Bariciano, Rebecca Otis, Rebekah R Herrmann, Reem Yunis, Reinette Hampson, Renato Abdala Karam, Renee C Hessian, Renee Kaneshiro, Reshma Ravindran, Reto Andreas Gamma, Reyna Bhandari, Reza Arsanjani, Ricardo L Lopes, Ricardo Mendes Oliveira, Ricardo Costa, Richa Bhatt, Richard F Davies, Richard H J Trimlett, Richard Goldweit, Rik Hermanides, Rine Nakanishi, Rinu R Sidh, Risha Patel, Rita Coram, Rizwan A Siddiqui, Rob S Beanlands, Robert J Hamburger, Robert K Riezebos, Robert M Donnino, Robert Bojar, Robert Chilton, Robert Guyton, Robert Henderson, Robert Kornberg, Robert Leber, Robert Mao, Robert Stenberg, Roberta P Santos, Roberto René Favaloro, Roberto Amati, Rodolfo G S D Lima, Rodrigo J Cerci, Rogerio Tumelero, Rohit Tandon, Roma Tewari, Romalisa Miranda-Peats, Ron Wald, Ronald A Mastouri, Ronald G Morford, Ronald G Schwartz, Ronald P Pedalino, Rongrong Hu, Ronnell A Hansen, Ronny A Cohen, Rory Hachamovitch, Rosa Homem, Rosa Sandonato, Rosane Laimer, Rosann Gans, Roxanne Yost, Roy Mathew, Rubén Baleón-Espinosa, Ruben Ramos, Rubine Gevorgyan, Rui Ferreira, Rui Jing, Ruth Pérez-Fernández, S K Dwivedi, S Ramakrishnan, Saadat Khan, Sabahat Bokhari, Sabu Thomas, Sadath Lubna, Sajeeda Parveen Khan, Sajeev Chakanalil Govindan, Saket Girotra, Saleem Kassam, Sallie Canada, Salvador Cruz-Flores, Samaa Mohamed, Samantha Ly, Sameh El Kaffas, Samia Massalha, Sampoornima Setty, Samuel Nwosu, Sandeep Seth, Sandeep Singh, Sander R Niehe, Sandra M Rivest, Sandra S Zier, Sandra Ahoud, Sandy Carr, Sanjay Ganapathi, Sanjay Shetty, Sanjeev Sharma, Santa Jimenez, Santhosh Satheesh, Santiago A Garcia, Sara Fernandez, Sara Karlsson, Sara Salkind, Sara Temiyasathit, Sarah Medina Rodriguez, Sarah Beaudry, Sarah Hadjih, Sarah Williams, Sarah Zahrani, Sarju Ralhan, Sasa Hinic, Sasko Kedev, Satinder Singh, Satoshi Yasuda, Satvic Cholenahally Manjunath, Sau Lee, Scott M Kaczkowski, Scott Kinlay, Sean W Hayes, Sebastian Sobczak, Senait Asier, Sergey A Sayganov, Seth I Sokol, Shaheen Pandie, Shaiful Azmi Yahaya, Shamir Mehta, Shao-Ping Nie, Sharad Chandra, Sharder Islam, Sharon Tai, Sheetal Rupesh Karwa, Sheri Ussery, Sheromani Bajaj, Sherron C Crook, Shigeyuki Nishimura, Shintaro Nakano, Shirin Heydari, Shiv Kumar Choudhary, Shivali Patel, Shobana Ganesan, Shruti Pandey, Shuyang Zhang, Shweta Hande, Siddharth Gadage, Sik-Yin V Tan, Silvia Zottis Poletti, Silvia Riera, Silvia Valbuena, Simon Walsh, Simona Maspoli, Simone Savaris, Si-Ting Feng, So Yang Cho, Solomon Yakubov, Songlin Zhu, Songtao Wang, Sonia Guerrero, Sonika Gupta, Sonja Salinger Martinovic, Sonya Brons, Sorin Brener, Sothinathan Gurunathan, Souheil Saba, Soundarya Nayak, Sowjanya Reddy, Srinivasa Potluri, Sriram Sudarshan, Srun Kuanprasert, Stacie Van Oosterhout, Stamatios Lerakis, Stanley E Cobos, Stefan C Bertog, Stefan M Simović, Stefan Weikl, Stefano Di Marco, Stefano Provasoli, Stephanie A Tirado, Stephanie C Boer, Stephanie M Lane, Stephanie Ferket, Stephanie Kelly, Stephanie Wasmiller, Stephen H McKellar, Stephen P Hoole, Stephen Fremes, Stephen Preston, Steve Leung, Steven A Fein, Steven J Lindsay, Steven P Sedlis, Steven Giovannone, Steven Michael, Steven Weitz, Stijn van Vugt, Subhash Banerjee, Sudhir Naik, Suellen Hosino, Sukie Desire, Sukit Yamwong, Suku T Thambar, Sulagna Mookherjee, Suman Singh, Sundeep Mishra, Sunil Kumar Verma, Supap Kulthawong, Supatchara Khwakhong, Surendra Naik, Suresh Babu, Surin Woragidpoonpol, Suryaprakash Narayanappa, Susan Derbyshire, Susan Gent, Susan Mathus, Susan Milbrandt, Susan Moore, Susan Regan, Susan Stinson, Susan Webber, Susana Silva, Susanna Stevens, Susanne Gruensfelder, Suthara Aramcharoen, Suvarna Kolhe, Suzana Tavares, Suzanne Arnold, Suzanne Welsh, Svetlana Apostolovic, Swapna Kunhunny, Ta-Chuan Hung, Taissa Zappernick, Tali Sharir, Talita Silva, Tamara Colaiácovo Soares, Tapan Umesh Pillay, Tarun K Mittal, Tatiana Trifonova, Tauane Bello Duarte, Tauqir Huk, Téodora Dutoiu, Terrance Chua, Terry Weyand, Thabitha Charles, Theodoros Kofidis, Theresa McCreary, Thierry Lefevre, Thippeekaa Arumairajah, Thitipong Tepsuwan, Thomas J Mulhearn, Thomas M Meyer, Thomas P Rocco, Thomas R Downes, Thomas Crain, Thomas Haldis, Thomas Mathew, Thomas Redick, Thounaojam Indira Devi, Thuraia Nageh, Tia Cauthren, Tiago Silva, Tiffany Little, Tijana Andric, Tina Harding, Titus Lau, Tiziana Formisano, Tiziano Moccetti, Tomasz Ciurus, Tomasz Mazurek, Tomasz Tarchalski, Toshiyuki Nagai, Tri Tran, Tricia Youn, Trish Tucker, Trudie Milner, Tuhina Bose, Tushar Kotecha, Udo Sechtem, Uma S Valeti, Umberto Cucchini, Umesh Badami, Upendra Kaul, V K Bahl, V S Narain, Valentina Casali, Valeria Godoy, Valerie Robesyn, Vamshi P Priya, Vandana Yadav, Vera McKinney, Veronica De Lenges, Veronica Tinnirello, Vicente Miro, Victor Navarro, Victoria Gumerova, Victoria Hernandez, Vidya Seeratan, Vijay Kumar, Vikentiy Y Kozulin, Viktoria Bulkley, Vilmar Veiga Jr, Vincent Setang, C P Vineeth, Virginai Pubull Nuñez, Virginia Fernández-Figares, Vitor Gomes, Viviana Gabriel, Viviane Dos Santos, Viviane Almeida, Vlad A Iliescu, Vladan Mudrenovic, Vladimir Dzavik, Vojislav L Giga, Walter Enrique Mogrovejo, Wan Xian Chan, Wanda C Marfori, Wanda Parker, Warangkana Mekara, Wassim Nona, Wayne Old, Wayne Pennachi, Weerachai Nawarawong, Wei Chen, Wei Su, Weibing Xing, Wei-Ren Lan, Wenda Crawford, Wendy L Stewart, Wendy Drewes, Wenhua Lin, William B Abernethy, William D Salerno, William F Fearon, William Vergoni, William Weintraub, Winnie C Sia, Wlodzimierz J Musial, Xacobe Flores-Ríos, Xavier Garcia-Moll Marimon, Xi Su, Xiang Ma, Xiangqiong Gu, Xiao Wang, Xiaomei Li, Xiaowei Yao, Xin Fu, Xin Su, Xin Zeng, Xinchun Yang, Xiuhong Li, Xuehua Fang, Xutong Wang, Yaming Geng, Yan Yan, Yanek Pépin-Dubois, Yanfu Wang, Yang Wang, Yanmeng Tian, Yaping Huang, Yechen Han, Yesenia Zambrano, Yi-Hsuan Yang, Ying Tung Sia, Yining Yang, Yitong Ma, Yolayfi Peralta, Yongjian Wu, Yu Kunwu, Yu Zhao, Yudong Peng, Yueh-Hung Lin, Yulan Zhao, Yumei Dong, Yunhai Zhao, Yutthaphan Wannasopha, Yvonne Taul, Zakir Sahul, Zalina Kudzoeva, Zbigniew Kalarus, Zeljko Z Markovic, Zhen Huang, Zheng Ji, Zhenyu Liu, Zhou Yue, Zhulin Zhang, Zhuxi Li, Zile Singh Meharwal, Ziliang Bai, Zixiang Yu, Zohra Huda, Zoltan Davidovits

Subjects
Male, Cardiac Catheterization, Computed Tomography Angiography, medicine.medical_treatment, Myocardial Ischemia, Coronary Disease, Coronary Artery Disease, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Coronary Angiography, ISCHEMIA Research Group, law.invention, Angina, Coronary artery disease, 0302 clinical medicine, Randomized controlled trial, law, Cardiovascular Disease, Myocardial Revascularization, 030212 general & internal medicine, Coronary Artery Bypass, 11 Medical and Health Sciences, Cardiac catheterization, General Medicine, Middle Aged, humanities, Cardiovascular Diseases, Cardiology, Female, Human, medicine.medical_specialty, Ischemia, Article, 03 medical and health sciences, Geriatric cardiology, Percutaneous Coronary Intervention, General & Internal Medicine, Internal medicine, medicine, Humans, Angina, Unstable, Aged, business.industry, Coronary Artery Bypa, Percutaneous coronary intervention, Bayes Theorem, medicine.disease, Heart failure, Quality of Life, business
Abstract

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

Published
2020
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23. Assessing the Relationship Between Molecular Rejection and Parenchymal Injury in Heart Transplant Biopsies

Author

Katelynn S. Madill-Thomsen, Jeff Reeve, Arezu Aliabadi-Zuckermann, Martin Cadeiras, Marisa G. Crespo-Leiro, Eugene C. Depasquale, Mario Deng, Johannes Goekler, Daniel H. Kim, Jon Kobashigawa, Peter Macdonald, Luciano Potena, Keyur Shah, Josef Stehlik, Andreas Zuckermann, and Philip F. Halloran

Subjects
Graft Rejection, Transplantation, Biopsy, Humans, Heart Transplantation, Kidney Transplantation, Antibodies
Abstract

The INTERHEART study (ClinicalTrials.gov #NCT02670408) used genome-wide microarrays to detect rejection in endomyocardial biopsies; however, many heart transplants with no rejection have late dysfunction and impaired survival. We used the microarray measurements to develop a molecular classification of parenchymal injury.In 1320 endomyocardial biopsies from 645 patients previously studied for rejection-associated transcripts, we measured the expression of 10 injury-induced transcript sets: 5 induced by recent injury; 2 reflecting macrophage infiltration; 2 normal heart transcript sets; and immunoglobulin transcripts, which correlate with time. We used archetypal clustering to assign injury groups.Injury transcript sets correlated with impaired function. Archetypal clustering based on the expression of injury transcript sets assigned each biopsy to 1 of 5 injury groups: 87 Severe-injury, 221 Late-injury, and 3 with lesser degrees of injury, 376 No-injury, 526 Mild-injury, and 110 Moderate-injury. Severe-injury had extensive loss of normal transcripts (dedifferentiation) and increase in macrophage and injury-induced transcripts. Late-injury was characterized by high immunoglobulin transcript expression. In Severe- and Late-injury, function was depressed, and short-term graft failure was increased, even in hearts with no rejection. T cell-mediated rejection almost always had parenchymal injury, and 85% had Severe- or Late-injury. In contrast, early antibody-mediated rejection (AMR) had little injury, but late AMR often had the Late-injury state.Characterizing heart transplants for their injury state provides new understanding of dysfunction and outcomes and demonstrates the differential impact of T cell-mediated rejection versus AMR on the parenchyma. Slow deterioration from AMR emerges as a major contributor to late dysfunction.

Published
2022

24. Evaluating age-based eligibility thresholds for heart re-transplantation - an analysis of the united network for organ sharing database

Author

Qiudong Chen, Jad Malas, Joshua Chan, Gabriel Esmailian, Dominic Emerson, Dominick Megna, Pedro Catarino, Michael E. Bowdish, Michelle Kittleson, Jignesh Patel, Joanna Chikwe, Jon Kobashigawa, and Fardad Esmailian

Subjects
Pulmonary and Respiratory Medicine, Transplantation, Surgery, Cardiology and Cardiovascular Medicine
Abstract

Risk-adjusted survival after late heart re-transplantation may be comparable to primary transplant, but the efficacy of re-transplantation in older candidates is not established. We evaluated outcomes after heart re-transplantation in recipients60 years.We identified 1026 adult patients undergoing isolated heart re-transplantation between 2003 and 2020 from the United Network for Organ Sharing database. Older recipients (60 years, n=177) were compared to younger recipients (≤ 60 years, n=849). Five and ten-year post-transplant survival was estimated using the Kalpan-Meier method and adjusted with multivariable Cox models.Older recipients were more likely to be male and have diabetes or previous malignancies with higher baseline creatinine. They also more frequently required pre-transplant ECMO (11.9% vs. 6.8%, p=0.02) and received re-transplantation due to primary graft failure (13.6% vs. 8.5%, p=0.03). After the transplant, older recipients had a higher incidence of stroke (6.8% vs. 2.6%, p=0.01) and dialysis requirements (20.3% vs. 13.2%) before discharge (both p0.05), and more frequently died from malignancy-related causes (16.3% vs. 3.9%, p0.001). After adjustment, recipient age60 was associated with an increased risk of both 5-year (HR 1.42, 95% CI 1.02-2.01, p=0.04) and 10-year mortality (HR 1.72, 95% CI 1.20-2.45, p=0.003). Restricted cubic spline showed a non-linear relationship between recipient age and 10-year mortality.Heart re-transplantation in recipients60 years has inferior outcomes compared to younger recipients. Strict patient selection and close follow-up are warranted to ensure the appropriate utilization of donor hearts and to improve long-term outcomes.

Published
2022

25. Heart transplantation after total artificial heart bridging-Outcomes over 15 years

Author

Qiudong Chen, Joshua Chan, Akbarshakh Akhmerov, Amy Roach, Dominic Emerson, Dominick Megna, Pedro Catarino, Jaime Moriguchi, David Chang, Michelle Kittleson, Dael Geft, Jon Kobashigawa, Joanna Chikwe, and Fardad Esmailian

Subjects
Adult, Heart Failure, Transplantation, Treatment Outcome, Humans, Heart Transplantation, Heart, Artificial, Heart-Assist Devices
Abstract

Data are limited on outcomes after heart transplantation in patients bridged-to-transplantation (BTT) with a total artificial heart (TAH-t).The UNOS database was used to identify 392 adult patients undergoing heart transplantation after TAH-t BTT between 2005 and 2020. They were compared with 11 014 durable left ventricular assist device (LVAD) BTT patients and 22 348 de novo heart transplants (without any durable VAD or TAH-t BTT) during the same period.TAH-t BTT patients had increased dialysis dependence compared to LVAD BTT and de novo transplants (24.7% vs. 2.7% vs. 3.8%) and higher levels of baseline creatinine and total bilirubin (all p .001). After transplantation, TAH-t BTT patients were more likely to die from multiorgan failure in the first year (25.0% vs. 16.1% vs. 16.1%, p = .04). Ten-year survival was inferior in TAH-t BTT patients (TAH-t BTT 53.1%, LVAD BTT 61.8%, De Novo 62.6%, p .001), while 10-year survival conditional on 1-year survival was similar (TAH-t BTT 66.8%, LVAD BTT 68.7%, De Novo 69.0%, all p .20). Among TAH-t BTT patients, predictors of 1-year mortality included higher baseline creatinine and total bilirubin, mechanical ventilation, and cumulative center volume20 cases of heart transplantation involving TAH-t BTT (all p .05).Survival after TAH-t BTT is acceptable, and patients who survive the early postoperative phase experience similar hazards of mortality over time compared to de novo transplant patients and durable LVAD BTT patients.

Published
2022

26. Heart transplantation using donation after circulatory death in the United States

Author

Qiudong Chen, Dominic Emerson, Dominick Megna, Asishana Osho, Amy Roach, Joshua Chan, Georgina Rowe, George Gill, Fardad Esmailian, Joanna Chikwe, Natalia Egorova, James K. Kirklin, Jon Kobashigawa, and Pedro Catarino

Subjects
Pulmonary and Respiratory Medicine, Surgery, Cardiology and Cardiovascular Medicine
Abstract

Heart donation after circulatory death was recently reintroduced in the United States with hopes of increasing donor heart availability. We examined its national use and outcomes.The United Network for Organ Sharing database was used to identify validated adult patients undergoing heart transplantation using donation after circulatory death donors (n = 266) and donation after brain death donors (n = 5998) between December 1, 2019, and December 31, 2021, after excluding heart-lung transplants. Propensity score matching was used to create more balanced groups for comparison.The monthly percentage of donation after circulatory death heart transplant increased from 2.5% in December 2019 to 6.8% in December 2021 (P .001). Twenty-two centers performed donation after circulatory death heart transplants, ranging from 1 to 75 transplants per center. Four centers performed 70% of the national volume. Recipients of donation after circulatory death hearts were more likely to be clinically stable (80.4% vs 41.1% in status 3-6, P .001), to have type O blood (58.3% vs 39.9%, P .001), and to wait longer after listing (55, interquartile range, 15-180 days vs 32, interquartile range, 9-160 days, P = .003). Six-month survival was 92.1% (95% confidence interval, 91.3-92.8) after donation after brain death heart transplants and 92.6% (95% confidence interval, 88.1-95.4) after donation after circulatory death heart transplants (hazard ratio, 0.94, 95% confidence interval, 0.57-1.54, P = .79). Outcomes in propensity-matched patients were similar except for higher rates of treated acute rejection in donation after circulatory death transplants before discharge (14.4% vs 8.8%, P = .01). In donation after circulatory death heart recipients, outcomes did not differ based on the procurement technique (normothermic regional perfusion vs direct procurement and perfusion).Heart transplantation with donation after circulatory death donors has short-term survival comparable to donation after brain death transplants. Broader implementation could substantially increase donor organ availability.

Published
2023
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27. Treatment of advanced heart failure in adults with congenital heart disease: a narrative review and clinical cases

Author

Christoph Sinning, Michael Huntgeburth, Norihide Fukushima, Rose Tompkins, June Huh, Shigeru Tataneo, Gerhard-Paul Diller, Yih-Sharng Chen, Elvin Zengin, Christina Magnussen, Ann-Sophie Kaemmerer, Yang Hyun Cho, Stefan Blankenberg, Carsten Rickers, Frank Harig, Michael Weyand, Michael Hübler, Yskert von Kodolitsch, Öztekin Oto, Andreas Zuckermann, Paulus Kirchhof, Helmut Baumgartner, Hermann Reichenspurner, Jon Kobashigawa, Harald Kaemmerer, and Koichiro Niwa

Subjects
Cardiology and Cardiovascular Medicine
Abstract

Background and Objective: The number of adults with congenital heart disease (ACHD) is increasing worldwide. Almost all congenital cardiac lesions can be successfully treated due to the progress in neonatal surgery and pediatric cardiology with a high likelihood of surviving until adulthood. However, ACHD frequently develop sequelae related to the initial cardiac anomaly. Heart failure (HF) is one of the most common complications associated with a high morbidity and mortality.Methods: The authors did search the PubMed database regarding relevant content covering publications up to March 2022. Relevant manuscripts were classified according to the impact factor of the journal, being a guideline manuscript, a position paper by a society or a comprehensive review of the current literature. Key content and findings: Optimal HF treatment remains an unmet need in ACHD. In particular, advanced HF therapy with cardiac resynchronization therapy, ventricular assist devices or organ transplantation is still very different and more specific in ACHD compared to non-ACHD. This review aims to compile international views and evidence from the literatures on the treatment of advanced HF in ACHD. Current challenges, but also the success of different treatment strategies in ACHD are illustrated by clinical cases.Conclusions: The main finding of the review is that data is still scarce regarding ACHD with advanced HF and international efforts to collect data regarding these patients needed to improve the current standard of care.

Published
2022

28. Trainee experience on ischemic times and outcomes following orthotopic heart transplantation

Author

Amy Roach, Alfredo Trento, Achille Peiris, Jon Kobashigawa, Fardad Esmailian, Joanna Chikwe, and Dominic Emerson

Subjects
Pulmonary and Respiratory Medicine, Surgery, Cardiology and Cardiovascular Medicine
Abstract

This study was designed to evaluate the association of surgical training on outcomes following orthotopic heart transplantation in all levels of cardiothoracic surgery fellows.A retrospective cohort analysis was performed on all heart transplants at a single institution from 2011 to 2020. Transplants performed using organ preservation systems (n = 10) or with significant missing data were excluded (n = 37), resulting in 154 transplants performed by faculty surgeons and 799 total transplants performed by first-year Accreditation Council for Graduate Medical Education fellows (n = 73), second-year Accreditation Council for Graduate Medical Education fellows (n = 124), or non-Accreditation Council for Graduate Medical Education fellows (n = 602) in a transplantation and mechanical circulatory support fellowship. Primary outcome was warm ischemic time analyzed by year of fellowship. Additional secondary outcomes included 30-day mortality, primary graft dysfunction, reoperation for bleeding, and 5-year survival. Median follow-up was 3 years (interquartile range [IQR], 1.0-5.5 years) and 100% complete.The median number of transplants performed was 30 (IQR, 19.5-51.8) during the study period performed by 22 trainees. Baseline transplant characteristics performed were similar amongst the trainee years, although the first-year Accreditation Council for Graduate Medical Education fellows approached significantly fewer re-do transplants (1.4% vs 8.1% and 4.3%; P = .07). Warm ischemic time was lower in the first-year fellows (49 minutes; IQR, 42-63 minutes) versus second-year fellows (56.5 minutes; IQR, 45.5-69 minutes) and mechanical circulatory support/transplant fellows (56 minutes; IQR, 46-67 minutes) (P = .028). Crossclamp time was also lower in the first-year fellows than in second-year and mechanical circulatory support/transplant fellows, respectively (79 minutes; IQR, 65-100 minutes vs 147 minutes; IQR, 125-176 minutes and 143 minutes; IQR, 119-175 minutes) (P = .008). Secondary outcomes, including 30-day mortality (4.1% [n = 3] vs 2.4% [n = 3] vs 2.7% [n = 16]; P = .76), primary graft dysfunction (5.5% [n = 4] vs 4.0% [n = 5] vs 4.3% [n = 26]; P = .88), reoperation for bleeding (2.7% [n = 2] vs 4.8% [n = 6] vs 4.2% [n = 25]; P = .78), and 5-year survival (82.2%; 95% CI, 66.7%-84.9% vs 77.3%; 95% CI, 66.7%-84.9% vs 79.3%; 95% CI, 74.9%-83.1%; P = .84) were comparable in all groups.This cohort of nearly 800 operations demonstrates that orthotopic heart transplantation may be performed by cardiac fellowship trainees all levels of training with acceptable short- and long-term outcomes.

Published
2022
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30. Coarctation of the aorta following repair in childhood at suprasternal view

Author

Christoph Sinning, Michael Huntgeburth, Norihide Fukushima, Rose Tompkins, June Huh, Shigeru Tataneo, Gerhard-Paul Diller, Yih-Sharng Chen, Elvin Zengin, Christina Magnussen, Ann-Sophie Kaemmerer, Yang Hyun Cho, Stefan Blankenberg, Carsten Rickers, Frank Harig, Michael Weyand, Michael Hübler, Yskert von Kodolitsch, Öztekin Oto, Andreas Zuckermann, Paulus Kirchhof, Helmut Baumgartner, Hermann Reichenspurner, Jon Kobashigawa, Harald Kaemmerer, and Koichiro Niwa

Subjects
Materials Chemistry
Published
2022
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31. Four-chamber view featuring the unrestrictive ventricular septal defect

Author

Christoph Sinning, Michael Huntgeburth, Norihide Fukushima, Rose Tompkins, June Huh, Shigeru Tataneo, Gerhard-Paul Diller, Yih-Sharng Chen, Elvin Zengin, Christina Magnussen, Ann-Sophie Kaemmerer, Yang Hyun Cho, Stefan Blankenberg, Carsten Rickers, Frank Harig, Michael Weyand, Michael Hübler, Yskert von Kodolitsch, Öztekin Oto, Andreas Zuckermann, Paulus Kirchhof, Helmut Baumgartner, Hermann Reichenspurner, Jon Kobashigawa, Harald Kaemmerer, and Koichiro Niwa

Subjects
Materials Chemistry
Published
2022
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32. Pretransplant four chamber view featuring the reconstructed tricuspid valve and the impaired ventricular function of the systemic right ventricle

Author

Christoph Sinning, Michael Huntgeburth, Norihide Fukushima, Rose Tompkins, June Huh, Shigeru Tataneo, Gerhard-Paul Diller, Yih-Sharng Chen, Elvin Zengin, Christina Magnussen, Ann-Sophie Kaemmerer, Yang Hyun Cho, Stefan Blankenberg, Carsten Rickers, Frank Harig, Michael Weyand, Michael Hübler, Yskert von Kodolitsch, Öztekin Oto, Andreas Zuckermann, Paulus Kirchhof, Helmut Baumgartner, Hermann Reichenspurner, Jon Kobashigawa, Harald Kaemmerer, and Koichiro Niwa

Subjects
Materials Chemistry
Published
2022
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33. Four-chamber view of the patient with color flow for the unrestrictive ventricular septal defect

Author

Christoph Sinning, Michael Huntgeburth, Norihide Fukushima, Rose Tompkins, June Huh, Shigeru Tataneo, Gerhard-Paul Diller, Yih-Sharng Chen, Elvin Zengin, Christina Magnussen, Ann-Sophie Kaemmerer, Yang Hyun Cho, Stefan Blankenberg, Carsten Rickers, Frank Harig, Michael Weyand, Michael Hübler, Yskert von Kodolitsch, Öztekin Oto, Andreas Zuckermann, Paulus Kirchhof, Helmut Baumgartner, Hermann Reichenspurner, Jon Kobashigawa, Harald Kaemmerer, and Koichiro Niwa

Subjects
Materials Chemistry
Published
2022
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34. Aneurysm of the aorta in the parasternal long axis view

Author

Christoph Sinning, Michael Huntgeburth, Norihide Fukushima, Rose Tompkins, June Huh, Shigeru Tataneo, Gerhard-Paul Diller, Yih-Sharng Chen, Elvin Zengin, Christina Magnussen, Ann-Sophie Kaemmerer, Yang Hyun Cho, Stefan Blankenberg, Carsten Rickers, Frank Harig, Michael Weyand, Michael Hübler, Yskert von Kodolitsch, Öztekin Oto, Andreas Zuckermann, Paulus Kirchhof, Helmut Baumgartner, Hermann Reichenspurner, Jon Kobashigawa, Harald Kaemmerer, and Koichiro Niwa

Subjects
Materials Chemistry
Published
2022
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35. Posttransplant 4-chamber view

Author

Christoph Sinning, Michael Huntgeburth, Norihide Fukushima, Rose Tompkins, June Huh, Shigeru Tataneo, Gerhard-Paul Diller, Yih-Sharng Chen, Elvin Zengin, Christina Magnussen, Ann-Sophie Kaemmerer, Yang Hyun Cho, Stefan Blankenberg, Carsten Rickers, Frank Harig, Michael Weyand, Michael Hübler, Yskert von Kodolitsch, Öztekin Oto, Andreas Zuckermann, Paulus Kirchhof, Helmut Baumgartner, Hermann Reichenspurner, Jon Kobashigawa, Harald Kaemmerer, and Koichiro Niwa

Subjects
Materials Chemistry
Published
2022
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36. Heart Transplantation With Older Donors: Should There Be an Age Cutoff?

Author

Qiudong Chen, Jon Kobashigawa, Dominic Emerson, Tahli Singer-Englar, Dominick Megna, Danny Ramzy, Pedro Catarino, Alfredo Trento, Joanna Chikwe, Michelle Kittleson, and Fardad Esmailian

Subjects
Adult, Transplantation, Heart Diseases, Age Factors, Humans, Heart Transplantation, Surgery, Kaplan-Meier Estimate, Middle Aged, Tissue Donors, Retrospective Studies
Abstract

Heart transplantation remains limited by donor availability. Currently, only some programs accept older donors, and their use remains contentious. We compared outcomes of heart transplant recipients who received donor hearts ≥55 years with those who received donor hearts55 years.Records of first-time adult heart transplant recipients between 2010 and 2019 were reviewed. Endpoints included 30-day and 1-, 3-, and 5-year survival; freedom from cardiac allograft vasculopathy; freedom from nonfatal major adverse cardiac events; and freedom from any rejections. The effect of donor age ≥55 years was analyzed with Cox proportional hazards modeling, 1:2 propensity score matching, and Kaplan-Meier survival analysis.Sixty-six patients received donor hearts ≥55 years and 766 received donor hearts55 years. In the unmatched cohort, there was no significant difference in survival between the 2 groups at 30 days (93.9% vs 97.3%, P = .127), 1 year (87.9% vs 91.6%, P = .325), 3 years (86.4% vs 86.5%, P = .888), or 5 years (78.8% vs 83.8%, P = .497). The ≥55 years group had a significantly lower freedom from cardiac allograft vasculopathy and fatal major adverse cardiac events. In propensity-matched patients, recipients of donors ≥55 years had similar survival and freedom from cardiac allograft vasculopathy but significantly lower 1-year (76.7% vs 88.3%, P = .026), 3-year (68.3% vs 84.2%, P = .010), and 5-year (63.3% vs 83.3%, P = .002) freedom from nonfatal major adverse cardiac events when compared to recipients of younger donors.Carefully selected older donors can be considered for a carefully selected group of recipients with acceptable outcomes.

Published
2021

37. Consensus conference on heart-kidney transplantation

Author

Jon, Kobashigawa, Darshana M, Dadhania, Maryjane, Farr, W H Wilson, Tang, Arvind, Bhimaraj, Lawrence, Czer, Shelley, Hall, Abdolreza, Haririan, Richard N, Formica, Jignesh, Patel, Rafael, Skorka, Savitri, Fedson, Titte, Srinivas, Jeffrey, Testani, Julie M, Yabu, Xingxing S, Cheng, and Mark, Zucker

Subjects
medicine.medical_specialty, Consensus, Heart disease, Renal function, Cardiorenal syndrome, 030230 surgery, Kidney, Organ transplantation, 03 medical and health sciences, 0302 clinical medicine, Immunology and Allergy, Medicine, Humans, Pharmacology (medical), Intensive care medicine, Kidney transplantation, Transplantation, business.industry, Consensus conference, Organ Transplantation, medicine.disease, Kidney Transplantation, Tissue Donors, United States, Heart Transplantation, business, Kidney disease
Abstract

Simultaneous heart-kidney transplant (sHK) has enabled the successful transplantation of patients with end-stage heart disease and concomitant kidney disease, with non-inferior outcomes to heart transplant (HT) alone. The decision for sHK is challenged by difficulties in differentiating those patients with a significant component of reversible kidney injury due to cardiorenal syndrome who may recover kidney function after HT, from those with intrinsic advanced kidney disease who would benefit most from sHK. A consensus conference on sHK took place on June 1, 2019 in Boston, Massachusetts. The conference represented a collaborative effort by experts in cardiothoracic and kidney transplantation from centers across the United States to explore the development of guidelines for the interdisciplinary criteria for kidney transplantation in the sHK candidate, to evaluate the current allocation of kidneys to follow the heart for sHK, and to recommend standardized care for the management of sHK recipients. The conference served as a forum to unify criteria between the different specialties and to forge a pathway for patients who may need dual organ transplantation. Due to the continuing shortage of available donor organs, ethical problems related to multi-organ transplantation were also debated. The findings and consensus statements are presented.

Published
2021

40. Reply

Author

Dominic Emerson, Joanna Chikwe, Pedro Catarino, Jon Kobashigawa, and James K. Kirklin

Subjects
Cardiology and Cardiovascular Medicine
Published
2021
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41. Incidence, characteristics, and outcome of post-heart transplant malignancy

Author

Jong-Chan Youn, In-Cheol Kim, Jin-Jin Kim, Sang Hong Baek, and Jon Kobashigawa

Subjects
endocrine system, medicine.medical_specialty, Lung, business.industry, Incidence (epidemiology), medicine.medical_treatment, Cancer, Immunosuppression, Malignancy, medicine.disease, medicine.anatomical_structure, Prostate, Internal medicine, Cancer screening, Medicine, Skin cancer, business
Abstract

Background: Post-transplant malignancy (PTM) has been an important cause of long-term morbidity and mortality in heart transplant (HTx) recipients. However, the detailed characteristics of PTM are largely unknown. We aimed to describe the charac teristics, outcomes, and predictors of de novo PTM in HTx recipients. Methods: We analyzed 989 consecutively enrolled HTx recipients without pre-transplant history of malignancy between 1997 and 2013. Main outcomes included the incidence, characteristics, outcomes, and predictors of PTM. Results: During a median follow-up period of 11.5 years, 206 patients (20.8%) had de novo PTMs (241 cancer cases). PTM pa tients, compared with non-PTM patients, showed older age, longer time on immunosuppression, and higher proportion of male and white patients. Skin cancers were the most frequent types of malignancy (60.6%) followed by prostate cancers (9.5%), lung cancers (7.1%), and breast cancers (4.1%). While most of the cancers (88.8%) were surgically resected at the initial presentation, about half of cancers (47.3%) showed recurrence or disease progression. Both patients with skin cancer and non-skin cancer, compared to patients without PTM, revealed a significantly lower overall survival (P

Published
2020
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42. Accelerated Allograft Vasculopathy With Rituximab After Cardiac Transplantation

Author

Randall C. Starling, Brian Armstrong, Nancy D. Bridges, Howard Eisen, Michael M. Givertz, Abdallah G. Kfoury, Jon Kobashigawa, David Ikle, Yvonne Morrison, Sean Pinney, Josef Stehlik, Sudipta Tripathi, Mohamed H. Sayegh, Anil Chandraker, Barbara Gus, Karen Keslar, Bill Magyar, John Petrich, W. H. Wilson Tang, Kimberly Brooks, Michael Givertz, Charles Kelly, Katie Klein, Kerry Crisalli, Sandra DeBronkart, Joren Madsen, Marc Semigran, John Vetrano, Teresa DeMarco, Scott Fields, Carol Maguire, Robert Gordon, Allen Anderson, Jane Regalado, Anna Warzecha, Lee Goldberg, Caroline Olt, Kenneth Rockwell, Ashley Harris, Maryl Johnson, Susan Johnston, Chris Roginski, Rashid Ahmed, Ivy Cohen, Denise Peace, Tina Yao, Gloria Araujo, Arvind Bhimaraj, Eunice Karanga, Varsha Patel, Julie Chait, Mario Deng, Gregg Fonarow, Christina Shin, Charles Gibbs, Judson Hunt, Melissa Johnson, Tina Worley, Jeff Gibbs, John Kirk, Winter Redd, Julia Bryan, Anna French, A.G. Kfoury, Kristin Konery, Erika Feller, Myounghee Lee, Richard Pierson, Cindi Young, Theodora Hollifield, Kimberley Porter, Mariann Schulz, Adrian VanBakel, Kiran Khush, Helen Luikart, Son Nguyen, Michael Pham, David DeNofrio, Ryan O’Kelly, Lucilla Garcia, Sean Sana, Brandy Starks, Maria Thottam, Annie Yi, Barry Cabuay, Rachel Olson, Larry Tucker, Laura Uppgaard, Denise Lai, Colleen Poisker, Klaudija Dragicevic, Harrison Kelner, Darlette Luke, Jennifer Nelson, Ganesh Raveendran, Nick Kleissas, Srinivas Murali, Kenneth Rayl, Sarah Sherry, and Michele Cosgrove

Subjects
Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Population, 030204 cardiovascular system & hematology, Placebo, Gastroenterology, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Postoperative Complications, Double-Blind Method, hemic and lymphatic diseases, Internal medicine, Intravascular ultrasound, medicine, Humans, Immunologic Factors, 030212 general & internal medicine, Prospective Studies, Vascular Diseases, education, CD20, education.field_of_study, medicine.diagnostic_test, biology, business.industry, Immunosuppression, Middle Aged, Allografts, Transplantation, Clinical trial, biology.protein, Heart Transplantation, Rituximab, Female, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

Background The CTOT-11 (Prevention of Cardiac Allograft Vasculopathy Using Rituximab Therapy in Cardiac Transplantation [Clinical Trials in Organ Transplantation-11]) study was a randomized, placebo-controlled, multicenter, double-blinded clinical trial in nonsensitized primary heart transplant (HTX) recipients. Objectives The study sought to determine whether B cell depletion therapy would attenuate the development of cardiac allograft vasculopathy. Methods A total of 163 HTX recipients were randomized to rituximab 1,000 mg intravenous or placebo on days 0 and 12 post-transplant. Primary outcome was change in percent atheroma volume (PAV) from baseline to 1 year measured by intravascular ultrasound. Secondary outcomes included treated episodes of acute rejection, de novo anti-HLA antibodies (including donor-specific antibodies), and phenotypic differentiation of B cells. Results There were no significant differences at study entry between the rituximab and placebo groups. Paired intravascular ultrasound measures were available at baseline and 1 year in 86 subjects (49 rituximab, 37 placebo). The mean ± SD change in PAV at 12 months was +6.8 ± 8.2% rituximab versus +1.9 ± 4.4% placebo (p = 0.0019). Mortality at 12 months was 3.4% rituximab versus 6.8% placebo (p = 0.47); there were no retransplants or post-transplant lymphoproliferative disorder. The rate of treated rejection was 24.7% rituximab versus 32.4% placebo (p = 0.28). Rituximab therapy effectively eliminated CD20+/CD19+ B cells followed by a gradual expansion of a CD19– cell population in the rituximab-treated group. Conclusions A marked, unexpected increase in coronary artery PAV with rituximab was observed during the first year in HTX recipients. One-year mortality was not impacted; however, longer-term follow-up and mechanistic explanations are required. (Prevention of Cardiac Allograft Vasculopathy Using Rituximab [Rituxan] Therapy in Cardiac Transplantation; NCT01278745)

Published
2018

43. Clinical Guide to Heart Transplantation

Author

Jon Kobashigawa and Jon Kobashigawa

Subjects
Heart--Transplantation
Abstract

This is a concise review of up-to-date concepts and techniques in the discipline of heart transplantation. It is a review and reference for practitioners managing patients with advanced heart disease, including patients with end-stage heart failure, mechanical circulatory support or transplant recipients. Heart failure is a major public health issue, with a prevalence of over 5.8 million in the USA, and over 23 million worldwide, and rising. The lifetime risk of developing heart failure is one in five. Heart failure carries substantial morbidity and mortality, with 5-year mortality that rival those of many cancers. As heart transplantation remains the best treatment option for patients with end stage heart failure, this primer will provide valuable information and management strategies for physicians caring for these patients. Also, due to continued shortage in donor organs, heart transplantation is a limited resource – which further underscores the importance of appropriately evaluating patients for transplant candidacy and managing their pre, peri- and post-transplant care for maximum benefit and best outcomes.​

Published
2017

44. Honoring 50 Years of Clinical Heart Transplantation in

Author

Josef, Stehlik, Jon, Kobashigawa, Sharon A, Hunt, Hermann, Reichenspurner, and James K, Kirklin

Subjects
Graft Rejection, Heart Failure, Graft Survival, Organ Preservation, Recovery of Function, History, 20th Century, History, 21st Century, Treatment Outcome, Risk Factors, Quality of Life, Tissue and Organ Harvesting, Animals, Heart Transplantation, Humans, Diffusion of Innovation, Immunosuppressive Agents
Abstract

Heart transplantation has become a standard therapy option for advanced heart failure. The translation of heart transplantation from innovative experiments to long-term clinical success has married prescient insights with discipline and organization in the domains of surgical techniques, organ preservation, immunosuppression, organ donation and transplantation logistics, infection control, and long-term graft surveillance. This review explores the key milestones of the past 50 years of heart transplantation and discusses current challenges and promising innovations on the clinical horizon.

Published
2017

45. A Review of the Management of Pregnancy After Cardiac Transplantation

Author

Diane D, Tran and Jon, Kobashigawa

Abstract

Success and advances in the management of all aspects of heart disease and heart transplantation have allowed for normalcy in life, including the question as to the possibility of pregnancy in transplantation. With the growing young adult population undergoing heart transplant, pregnancy and transplantation have become an issue of importance. Despite the fact that nearly 50 years have passed since the first heart transplant, there remains to be little evidence in regard to management of pregnant heart transplant recipients. Thus, this review will address issues related to pregnancy in this patient population, such as preconception counseling, timing and optimization for pregnancy post transplant, immunosuppression, cardiac assessment, and management of pregnant heart transplant recipients, as well as hemodynamic effects of pregnancy on the transplanted heart. Based on the available literature from registrar data, case reports and series, with careful planning, monitoring, and appropriate therapies, pregnancy in heart transplantation is a viable option in select patients. To optimize maternal and fetal outcomes, recommendations are included in this review to minimize complications including rejection, graft dysfunction, maternal diabetes and hypertension, as well as appropriate changes in immunosuppression.

Published
2017

46. Clinical and Angiographic Outcomes with Everolimus Eluting Stents for the Treatment of Cardiac Allograft Vasculopathy

Author

Jon Kobashigawa, Raj Makkar, Amelia Young, Babak Azarbal, B S Matthew Rafiei, Michelle M. Kittleson, Lawrence Czer, Boris Arbit, Radhakrishnan Ramaraj, and Jesse Currier

Subjects
medicine.medical_specialty, Everolimus, business.industry, medicine.medical_treatment, Percutaneous coronary intervention, Stent, medicine.disease, Coronary artery disease, Stenosis, Restenosis, Internal medicine, Conventional PCI, medicine, Cardiology, Radiology, Nuclear Medicine and imaging, Radiology, Myocardial infarction, Cardiology and Cardiovascular Medicine, business, medicine.drug
Abstract

Objectives: This study aimed to examine clinical efficacy, safety, and intermediate clinical outcomes with everolimus‐eluting stents (EESs) in patients with transplant coronary artery disease (TCAD). Background: TCAD is a major cause of mortality in patients following orthotopic heart transplantation (OHT). Systemic everolimus in OHT patients hasbeen shown to reduce TCAD. The safety and efficacy of an EES, the Xience V, have not been evaluated in this population. Methods: Patients post‐OHT with hemodynamically significant CAD who underwent percutaneous coronary intervention (PCI) with EES were included. Participants were maintained on dual antiplatelet therapy for 1‐year post‐PCI. We examined procedural success, in‐hospital and 1‐year mortality, stent thrombosis, angiographic restenosis, and myocardial infarction rates. All patients had follow‐up angiography 1‐year after PCI. Target vessel revascularization (TVR), target lesion revascularization (TLR), in‐segment restenosis, target vessel failure (TVF), and lumen late loss were noted. Results: PCI was performed in 34 de novo lesions in 21 patients, and 40 EES were placed. Procedural success rate was 100%. Average stent was 16.5 � 5.1mm long and 3.0 � 0.6mm in diameter. All patients had angiographic follow‐up(409 � 201days).Therewasnostentthrombosis,deaths,ormyocardialinfarctionsduringfollow‐up.Two patients had focal in‐stent restenosis. TLR rate was 5.9% (2/34), and TVR rate was 11.1% (3/27). Quantitative coronary angiography (QCA) showed stenosis diameter to be 19.98 � 17.57%. Conclusions: Use of an EES is associated with a low incidence of TVR and TLR in patients with TCAD. Further studies are needed to determine whether PCI with EES changes long‐term outcomes. (J Interven Cardiol 2014;27:73–79)

Published
2013
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47. In vivo diffusion-tensor MRI of the human heart on a 3 tesla clinical scanner: An optimized second order (M2) motion compensated diffusion-preparation approach

Author

Christopher, Nguyen, Zhaoyang, Fan, Yibin, Xie, Jianing, Pang, Peter, Speier, Xiaoming, Bi, Jon, Kobashigawa, and Debiao, Li

Subjects
Adult, Heart Failure, Male, Cardiac-Gated Imaging Techniques, Reproducibility of Results, Heart, Signal Processing, Computer-Assisted, Image Enhancement, Sensitivity and Specificity, Article, Motion, Diffusion Tensor Imaging, Image Interpretation, Computer-Assisted, Humans, Female, Artifacts, Algorithms, Aged
Abstract

To optimize a diffusion-prepared balanced steady-state free precession cardiac MRI (CMR) technique to perform diffusion-tensor CMR (DT-CMR) in humans on a 3 Tesla clinical scanner METHODS: A previously developed second order motion compensated (M2) diffusion-preparation scheme was significantly shortened (40%) yielding sufficient signal-to-noise ratio for DT-CMR imaging. In 20 healthy volunteers and 3 heart failure (HF) patients, DT-CMR was performed comparing no motion compensation (M0), first order motion compensation (M1), and the optimized M2. Mean diffusivity (MD), fractional anisotropy (FA), helix angle (HA), and HA transmural slope (HATS) were calculated. Reproducibility and success rate (SR) were investigated.M2-derived left ventricular (LV) MD, FA, and HATS (1.4 ± 0.2 μmThe proposed M2 DT-CMR reproducibly yielded bulk motion robust estimations of mean LV MD, FA, HA, and HATS on a 3T clinical scanner. Magn Reson Med 76:1354-1363, 2016. © 2016 International Society for Magnetic Resonance in Medicine.

Published
2016

48. Proceedings of the AST heart allocation meeting at the American Transplant Congress, Philadelphia, Pennsylvania, May 4, 2015

Author

Jon, Kobashigawa, Jeffrey, Teuteberg, Monica, Colvin, Leah, Edwards, Tiffany, Daun, Minh, Luu, Jignesh, Patel, John David, Vega, Dan, Meyer, and Jessica, Zeglin

Subjects
Prioritization, medicine.medical_specialty, Tissue and Organ Procurement, Heart Diseases, Waiting Lists, Management of heart failure, 030204 cardiovascular system & hematology, 030230 surgery, Resource Allocation, 03 medical and health sciences, 0302 clinical medicine, Public discussion, Directed Tissue Donation, medicine, Humans, Transplantation, Health Care Rationing, Cardiothoracic surgeons, business.industry, Congresses as Topic, medicine.disease, United States, Surgery, Disadvantaged, Organ procurement, Heart Transplantation, Medical emergency, Waitlist mortality, business
Abstract

Ensuring fair and equitable allocation of donor hearts in the US is the charge of the Organ Procurement and Transplantation Network (OPTN). However, the recent increase of candidates waiting without a corresponding increase in available donors, higher waitlist mortality rates in higher status patients, the presence of disadvantaged subgroups, and the changing management of heart failure patients with increased VAD usage, has necessitated review of allocation policy. Therefore, the Heart Subcommittee of the OPTN/UNOS Thoracic Committee is exploring a further-tiered allocation system, devising a "straw man" model as a starting point for modeling analyses and public discussion. On May 4, 2015, an American Society of Transplantation (AST)-endorsed forum to discuss these potential proposed changes took place. Attendees included 41 people, mostly highly experienced transplant cardiologists and cardiothoracic surgeons, representing 19 heart transplant centers across the US, UNOS, and the Scientific Registry of Transplant Recipients (SRTR). There was unanimous agreement that the potential proposed policy will require careful wording to avoid ambiguity and "gaming" of the system, and strong support for abolishment of local organ sharing in favor of geographic sharing. However, contention existed concerning the appropriate prioritization levels of ECMO, temporary VAD/TAH patients as well as the 30-day LVAD listing.

Published
2016

49. Abstract 14780: The First Hundred Days: Gender Differences in Psychosocial Distress After Heart Transplant

Author

Lynn Doering, Belinda Chen, Kathleen Hickey, Erik Carter, Carmen Castillo, David Pickham, Donna Mancini, Mario Deng, Jon Kobashigawa, and Barbara Drew

Subjects
Physiology (medical), Cardiology and Cardiovascular Medicine
Abstract

Early psychological distress after heart transplant (HTx) is associated with adverse outcomes (e.g. poorer medical compliance, higher risk of infection). In the HTx population, gender effects of depression and anxiety symptoms are controversial. Our objective was to examine gender differences in psychosocial measures early after HTx. Methods: We enrolled 91 adult HTx patients (29% female, mean age=51 ± 14 years) who completed measures of depression (Patient Health Questionnaire [PHQ]-9), anxiety (Brief Symptom Inventory [BSI]), perceived control (Control Attitudes Scale-Revised) and quality of life (QOL) (RAND-36 Health Survey) in the first 100 days after HTx (mean time from HTx = 50 ± 24 days). Hierarchical multiple linear regression models were used to examine gender influences on depression, anxiety, control, and QOL. Results: Compared to men, women are more likely to experience high depressive symptoms (15% vs. 39%, p=0.02), high levels of anxiety (46% vs.77%, p=0.008), and low perceived control (average score 33 vs. 29, p=0.007). For both men and women, anxiety is more prevalent than depressive symptoms (Figure). Compared to men, women had lower QOL due to pain (p=0.045) and limitations from emotional problems (p=0.02). In linear regression analyses, the effect of gender remained significant on depression (p=0.003), anxiety (p=0.03), and perceived control (p=0.02), but not QOL, after controlling for demographics (age, marital status, race, time between HTx and questionnaire completion, and Charlson Comorbidity Index). Conclusion: In the first 100 days after HTx, women experience more depressive and anxiety symptoms and less control over their heart health than men. Clinicians should monitor these symptoms early after HTx, especially in women. Development of gender-specific interventions aimed at a smooth post-HTx transition are warranted. Future research is needed to evaluate the relationship of anxiety and depressive symptoms before and after HTx.

Published
2015
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50. Revision of the 1990 Working Formulation for the Standardization of Nomenclature in the Diagnosis of Heart Rejection

Author

Susan Stewart, Gayle L. Winters, Michael C. Fishbein, Henry D. Tazelaar, Jon Kobashigawa, Jacki Abrams, Claus B. Andersen, Annalisa Angelini, Gerald J. Berry, Margaret M. Burke, Anthony J. Demetris, Elizabeth Hammond, Silviu Itescu, Charles C. Marboe, Bruce McManus, Elaine F. Reed, Nancy L. Reinsmoen, E. Rene Rodriguez, Alan G. Rose, Marlene Rose, Nicole Suciu-Focia, Adriana Zeevi, and Margaret E. Billingham

Subjects
Graft Rejection, Pulmonary and Respiratory Medicine, Muscle Cells, Transplantation, Biopsy, Myocardium, Immunohistochemistry, Terminology as Topic, Heart Transplantation, Humans, Transplantation, Homologous, Surgery, Cardiology and Cardiovascular Medicine, Endocardium
Abstract

In 1990, an international grading system for cardiac allograft biopsies was adopted by the International Society for Heart Transplantation. This system has served the heart transplant community well, facilitating communication between transplant centers, especially with regard to patient management and research. In 2004, under the direction of the International Society for Heart and Lung Transplantation (ISHLT), a multidisciplinary review of the cardiac biopsy grading system was undertaken to address challenges and inconsistencies in its use and to address recent advances in the knowledge of antibody-mediated rejection. This article summarizes the revised consensus classification for cardiac allograft rejection. In brief, the revised (R) categories of cellular rejection are as follows: Grade 0 R--no rejection (no change from 1990); Grade 1 R--mild rejection (1990 Grades 1A, 1B and 2); Grade 2 R--moderate rejection (1990 Grade 3A); and Grade 3 R--severe rejection (1990 Grades 3B and 4). Because the histologic sub-types of Quilty A and Quilty B have never been shown to have clinical significance, the "A" and "B" designations have been eliminated. Recommendations are also made for the histologic recognition and immunohistologic investigation of acute antibody-mediated rejection (AMR) with the expectation that greater standardization of the assessment of this controversial entity will clarify its clinical significance. Technical considerations in biopsy processing are also addressed. This consensus revision of the Working Formulation was approved by the ISHLT Board of Directors in December 2004.

Published
2005
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