JHLT: The Podcast

The JHLT Digital Media Editors explore two manuscripts from the August issue of The Journal of Heart and Lung Transplantation—the first on immunosuppression in pediatric heart transplantation, and the second TA-NRP in DCD lung transplantation. Digital Media Editor Van-Khue Ton, MD, heart failure and transplant cardiologist at Massachusetts General Hospital, hosts this episode.

First, hear from senior author Steven C. Greenway, MSc, MD, on his team's study "Single-drug immunosuppression is associated with noninferior medium-term survival in pediatric heart transplant recipients." Dr. Greenway shares his journey from enzyme biochemistry in mollusks, snails, and frogs to pediatric cardiology, then outlines the results of the paper.

The study queried the Pediatric Heart Transplant Society's registry to determine the efficacy and safety of monotherapy immunosuppression. The results showed better graft survival and less coronary allograft vasculopathy in the monotherapy group, even after adjusted for age at transplant, sex, neonatal transplant, infection, PTLD, and etiology of cardiomyopathy. Dr. Greenway and the digital media editors discuss the burning questions that obviously arise from the study's findings, the limitations of the paper, and what follow-up studies might start generating the answers that might eventually change clinical practice.

Next, the editors welcome first author Jad Malas, MD, to discuss the paper "The impact of thoracoabdominal normothermic regional perfusion on early outcomes in donation after circulatory death lung transplantation." This study utilized the United Network of Organ Sharing (UNOS) database to identify DCD donors whose heart was procured in order to evaluate lung utilization rates and early post-lung transplant outcomes. Lung utilization was similar between the groups—14.9% for the NRP group and 13.8% for direct procurement. Post-lung transplant rates of ECMO and mechanical ventilation at 72 hours were not statistically different, and 6-month survival was equivalent.

Dr. Malas and the Digital Media Editors discuss the study's findings and implications, including exploring the background of NRP's relationship to lung allografts, differences in assessment or procurement techniques, and what might be needed to further evaluate this procurement technique for lung allografts.

Follow along at www.jhltonline.org/current, or, if you're an ISHLT member, log in at ishlt.org/journal-of-heart-lung-transplantation. Don't already get the Journal and want to read along? Join the International Society of Heart and Lung Transplantation at www.ishlt.org for a free subscription, or subscribe today at www.jhltonline.org.

This episode of JHLT: The Podcast, but not the studies within, is sponsored by Natera.

The JHLT Digital Media Editors explore two manuscripts from the July issue of The Journal of Heart and Lung Transplantation—one on heart transplantation and one on lung transplantation. Digital Media Editor Marty C. Tam, MD, Assistant Professor at the University of Michigan, hosts this episode.

First, hear from co-first author Kevin Chen, MD, on his team's study "Donation after circulatory death heart procurement strategy impacts utilization and outcomes of concurrently procured abdominal organs," which comes from Cedars-Sinai. The study looks into the results of DCD organ donation depending on the technique used at procurement, mainly comparing ex-situ normothermic organ perfusion with thoracoabdominal normothermic regional perfusion (TA-NRP).

Digital Media Editors David Schibilsky, MD, and Van-Khue Ton, MD, have questions on the relationship between DCD liver and kidney procurement and heart procurement strategies, why TA-NRP livers and kidneys might differ, and the lower incidence of delayed graft function in DCD kidney transplants with TA-NRP. Dr. Chen also shares some thoughts about how this work might be incorporated into clinical practice.

Next, the editors welcome first author Jonathan P. Singer, MD, MS, from UCSF, to discuss the paper "Development of the Lung Transplant Frailty Scale (LT-FS)." Based on previous work, Dr. Singer and his colleagues set out to develop a novel frailty scale specifically for lung transplant candidates with improved performance characteristics over other frailty scales. The authors developed three lung transplant frailty measures and compared the construct and predictive validity to the existing short physical performance battery (SPPB) and the fried frailty phenotype (FFP). Their LT-FS models exhibited superior construct and predictive validity to these measures—and the addition of muscle mass and biomarkers further improved the model's performance.

Digital Media Editor Erika Lease, MD, digs in with Dr. Singer on the main findings of the study. What's unique about patients with advanced lung disease that makes them need a more specific frailty scale? How does the LT-FS outshine prior models? And what are the barriers to implementing a new model like this one in a transplant center?

Follow along at www.jhltonline.org/current, or, if you're an ISHLT member, log in at ishlt.org/journal-of-heart-lung-transplantation. Don't already get the Journal and want to read along? Join the International Society of Heart and Lung Transplantation at www.ishlt.org for a free subscription, or subscribe today at www.jhltonline.org.

On the June episode of JHLT: The Podcast, the Digital Media Editors explore two manuscripts from the June issue of The Journal of Heart and Lung Transplantation, with authors from the US and Denmark.

First, hear from senior author Steven R. Hays, MD, on his team's study "Design and implementation of a digital health home spirometry intervention for remote monitoring of lung transplant function," which explores digital health and comes out of UCSF. In the study, the authors developed an automated digital health intervention using Bluetooth-enabled home spirometers to monitor for complications after lung transplantation. Using a chat-based application, patients could perform home spirometry, answer symptom queries, and receive patient education. The program could also alert both the patient and center providers to substantial decreases in FEV1 from baseline—and any other concerning symptoms.

Dr. Hays and Digital Media Editors Erika Lease, MD, and Van-Khue Ton, MD, PhD, discuss how COVID-19 created a serendipitous moment to fund the study, and some of the most valuable lessons from the rollout of the program, including creating efficiencies among the transplant team, proper resourcing, and next steps for perfecting the program.

Next, the editors welcome first author Niels Moeslund, MD, PhD, from Aarhus University in Denmark, to discuss the paper, "Ex-situ oxygenated hypothermic machine perfusion in donation after circulatory death heart transplantation following either direct procurement or in-situ normothermic regional perfusion." In the study, authors set out to explore the use of oxygenated hypothermic machine perfusion as an alternative to in-situ normothermic regional perfusion or ex-situ normothermic machine perfusion of DCD hearts. They used a porcine model to simulate a DCD setting, and performed either normothermic regional perfusion and static cold storage; normothermic regional perfusion with hypothermic machine perfusion with the XVIVO heart preservation system; or direct procurement with hypothermic machine perfusion—all before heart transplantation was performed.

Digital Media Editor David Schibilsky, MD, digs in with Dr. Moeslund on the main findings of the study, in which HMP hearts showed better contractility after transplantation despite significantly lower inotropic support. Why? Dr. Moeslund shares that the hypothermia of HMP keeps metabolic activity low while myocytes are being replenished, creating maximum potential for energy restoration.

Follow along at www.jhltonline.org/current, or, if you're an ISHLT member, log in at ishlt.org/journal-of-heart-lung-transplantation. Don't already get the Journal and want to read along? Join the International Society of Heart and Lung Transplantation at www.ishlt.org for a free subscription, or subscribe today at www.jhltonline.org.

On May's JHLT: The Podcast, we feature two manuscripts from the May issue of The Journal of Heart and Lung Transplantation.

First, the editors explore a study entitled "Donor hyperoxia is a novel risk factor for severe cardiac primary graft dysfyunction," which comes from Kransdorf and colleagues at Cedars Sinai Medical Center in Los Angeles.

The editors welcome first author Evan Kransdorf, MD, PhD, to share how he transitioned from oncology to heart failure and transplantation, and to talk about the findings of the study. The Digital Media Editors want to know how machine learning came to be a part of the study, what other donor-specific predictors might contribute to severe PGD, and whether DCD and DBD donors had different outcomes.

Next, the editors welcome first author Danny Ramzy, MD, PhD, from the UTHealth McGovern School of Medicine in Houston to discuss the paper, "Improved clinical outcomes associated with the Impella 5.5 compared to the Impella 5.0 in contemporary cardiogenic shock and heart failure patients."

The digital media editors dig in with Dr. Ramzy on why Impella 5.5 has better outcomes and if this outcome holds in multivariable models, why the survival outcomes were so much higher than published survivals for patients with cardiogenic shock, and what follow up studies might get the answers they're looking for.

Follow along at www.jhltonline.org/current, or, if you're an ISHLT member, log in at ishlt.org/journal-of-heart-lung-transplantation. Don't already get the Journal and want to read along? Join the International Society of Heart and Lung Transplantation at www.ishlt.org for a free subscription, or subscribe today at www.jhltonline.org.

El podcast de JHLTenEspañol: presentamos por primera vez un podcast de JHLT en Español, conducido por Marta Farrero, MD, PhD, en el que repasamos 4 artículos destacados de 2022, cada uno centrado en el foco de interés de las redes interdisciplinarias de ISHLT.

El artículo sobre soporte circulatorio se titula "La recuperación de la función ventricular se asocia con mejores resultados en asistencia ventricular", con Cameron Olsen, MD, como primer firmante, y es comentado por el Sebastián Rojas, MD. Se analiza el impacto clínico favorable de la recuperación de la fracción de eyección por encima del 40% en una cohorte retrospectiva de pacientes con implante de asistencia ventricular de larga duración.

El artículo sobre trasplante pulmonar se titula "Síndrome del injerto restrictivo vs bronquiolitis obliterante: caracterización inmunológica y molecular de exosomas circulantes", con Sandhya Bansal, PhD primer firmante, comentado por Alejandro Bertolotti, MD. Este trabajo se propone tratar de caracterizar la patogenia del rechazo crónico analizando el contenido de moléculas proinflamatorias y potencialmente inmunogénicas contenidas en exosomas aislados del plasma de receptore de trasplante pulmonar.

El artículo sobre hipertensión pulmonar se titula "Escalas de riesgo y predicción clínica en hipertensión arterial pulmonar, un análisis del freedom-EV" con de Raymond L. Benza, MD como primer firmante y Roberto Bernardo, MD, MS para realizar los comentarios. En este subanálisis se observa como las escalas de riesgo de los pacientes con hipertensión pulmonar mejoran tras la administración de treprostinil oral.

El cuarto y último artículo se titula "MicroRNA circulante y rechazo mediado por anticuerpos en el trasplante cardíaco", con Palak Shah, MD, MS como primer firmante y comentado por Vanessa Blumer, MD. En este trabajo se identificó qué microRNA se asocian a rechazo celular y mediado por anticuerpos, permitiendo hacer el diagnóstico con una buena sensibilidad y especificidad.

It's another COVID-19 special on this month's JHLT: The Podcast, which features two articles on COVID-19 and thoracic organ transplantation from the April issue of The Journal of Heart and Lung Transplantation.

First, the editors explore a study entitled "Heart transplantation for COVID-19 myopathy in the United States," which comes from Gill and colleagues at Cedars Sinai Medical Center in Los Angeles.

The editors welcome first author George Gill, MD, to share what brought him from the United Kingdom to the States, and to talk about the findings of the study. The Digital Media Editors want to know how COVID-19 myocarditis impacts immune response in transplantation, how Dr. Gill manages different etiologies of cardiomyopathy, and some of the limitations of the study.

Next, the editors welcome senior author Nicolaus Schwerk, MD, from Hannover Medical School in Germany to discuss the paper, "COVID-19 in pediatric lung transplant recipients: Clinical Course and outcome."

Dr. Schwerk is an expert in rare diffuse parenchymal lung diseases and end stage lung diseases, as well as congenital thoracic malformations in children, and performs lung transplantation. This single-center study investigated the impact of SARS-COV-2 infection on pediatric lung transplant recipients between March 2020 and June 2022 at Hannover Medical Center. The key finding of the study was that the COVID-19-positive pediatric lung transplant recipients did remarkably well.

The digital media editors dig in with Dr. Schwerk on the pace of COVID-19 infections in Europe, why antivirals are used differently in pediatric patients, and why pediatric patients typically experience a more mild course of disease.

Follow along at www.jhltonline.org/current, or, if you're an ISHLT member, log in at ishlt.org/journal-of-heart-lung-transplantation. Don't already get the Journal and want to read along? Join the International Society of Heart and Lung Transplantation at www.ishlt.org for a free subscription, or subscribe today at www.jhltonline.org.

This month's JHLT: The Podcast is hosted by Digital Media Editor David Schibilsky, MD, who leads a discussion of two studies from the March issue of The Journal of Heart and Lung Transplantation—and the first authors who presented them.

First, the editors explore a study entitled "Angiopoietin 2 and hsCRP are associated with pulmonary hemodynamics and long-term mortality respectively in CTEPH—Results from a prospective discovery and validation biomarker study," which comes from Hadinnapola and colleagues at the Papworth group in Cambridge, UK.

The editors welcome Charaka Hadinnapola, MA, MB, BChir, first author on the CTEPH study, to share the rationale in performing the research, its main findings, the changing understanding of the pathobiology of pulmonary arterial hypertension, and how Ang2 and hsCRP fit into the bigger cytokine picture in CTEPD and CTEPH patients.

Next, the editors welcome author J.K. Peel, MD, MSc, from the University of Toronto to discuss the paper her first authored, "Determining the impact of ex-vivo lung perfusion on hospital costs for lung transplantation: a retrospective cohort study."

This retrospective, before-after, propensity-score weighted cohort study explores how EVLP affects hospital costs and the associated transplant procedures, intending to evaluate whether the benefits of EVLP offset its additional cost. Dr. Peel shares what changes occurred at his center during the study period, how the results compare to other published evidence on EVLP costs, and whether the results are transferable to smaller centers.

Follow along at www.jhltonline.org/current, or, if you're an ISHLT member, log in at ishlt.org/journal-of-heart-lung-transplantation. Don't already get the Journal and want to read along? Join the International Society of Heart and Lung Transplantation at www.ishlt.org for a free subscription, or subscribe today at www.jhltonline.org.

This month on JHLT: The Podcast, the JHLT Digital Media Editors review two studies from the February issue of The Journal of Heart and Lung Transplantation—and bring in a couple of experts to help them make sense of some new technology.

First, the editors explore a pre-clinical study entitled "The dynamic cellular landscape of grafts with acute rejection after heart transplantation," which comes from Kong and colleagues at Zhejiang University in Hangzhou, China.

Single cell technologies are emerging as non-biased techniques to discover novel biological pathways in a variety of pre-clinical models and in human tissue both in health and disease. To help the editors—and you!—understand single cell approaches and this study, JHLT editors Ben Kopecky, MD, PhD and Kory Lavine, MD, PhD, from the Washington University St. Louis, appear in the episode to explore the methodology and what the study tells us.

Second, the editors welcome author Sam Rayner, MD from the University of Washington in Seattle, USA, to discuss the paper by Hirsch and colleagues, "Circulating markers of inflammation and angiogenesis and clinical outcomes across subtypes of pulmonary arterial hypertension."

When considering differences in pathophysiology of the subtypes of PAH, changes in biomarkers in angiogenesis and inflammation may provide useful insights and potential therapeutic targets. The authors of this study prospectively looked at 33 biomarkers of angiogenesis and inflammation in a cohort of patients across various PAH etiologies, and made correlations to clinical outcomes.

Follow along at www.jhltonline.org/current, or, if you're an ISHLT member, log in at ishlt.org/journal-of-heart-lung-transplantation. Don't already get the Journal and want to read along? Join the International Society of Heart and Lung Transplantation at www.ishlt.org for a free subscription, or subscribe today at www.jhltonline.org.

JHLT: The Podcast kicks off 2023 with a look back at 2022. Daniel R. Goldstein, MD, Editor-in-Chief of JHLT, joins the JHLT Digital Media Editors for a recap of the past year of The Journal of Heart and Lung Transplantation.

Studies include:

• Pérez-Carrillo, et al, "Diagnostic value of serum miR-144-3p for the detection of acute cellular rejection in heart transplant patients." Feb 2022 JHLT
• Han, et al, "Impact of using higher-risk donor hearts for candidates with pre-transplant mechanical circulatory support." Feb 2022 JHLT
• Jackson, et al, "Heart transplant outcomes in cardiac sarcoidosis." Jan 2022 JHLT
• Ribeiro, et al, "Ex vivo treatment of cytomegalovirus in human donor lungs using a novel chemokine-based immunotoxin." Mar 2022 JHLT
• Moshkelgosha, et al, "Interferon-stimulated and metallothionein expressing macrophages are associated with acute and chronic allograft dysfunction after lung transplantation." Nov 2022 JHLT

Follow along at www.jhltonline.org/current, or, if you're an ISHLT member, log in at ishlt.org/journal-of-heart-lung-transplantation. Don't already get the Journal and want to read along? Join the International Society of Heart and Lung Transplantation at www.ishlt.org for a free subscription, or subscribe today at www.jhltonline.org.

This month on JHLT The Podcast, JHLT Digital Media Editor Marty Tam, MD, takes over hosting duties to present two papers from the December issue of The Journal of Heart and Lung Transplantation. Listen now to hear study authors discuss their work, their studies, and next steps for their research.

First, we welcome first author Jorge V. López-Ibor, MD, and senior author Javier Segovia-Cubero, MD, PhD, about their team's study from Hospital Universitario Puerto de Hierro Majadahonda entitled "Role of TGF-β1 +869T>C polymorphism in renal dysfunction one year after heart transplantation." Drs. López-Ibor and Segovia-Cubero share some background on their work and their areas of research before diving into the study.

The study analyzed 355 adult patients for renal dysfunction a year post-heart transplant and suggested a protective role for the TGF- β1 + 869CC genotypes in the development of chronic kidney disease (CKD) in heart transplant patients on calcineurin inhibitors (CNIs).

Next, Tsuyoshi Takahashi, MD, PhD, from Washington University, shares details on the study "A comparison of outcomes after lung transplantation between European and North American centers." Dr. Takahashi begins by discussing his global journey in thoracic surgery, including some of the differences between being a surgeon in the United States and Japan.

The study used the ISHLT Thoracic Organ Registry to complete a retrospective, comparative cohort analysis of adult patients undergoing deceased donor lung transplant in North America and Europe between January 2006 and December 2016. It compared overall survival between North American and European transplant centers in a propensity score matched analysis, suggesting a higher 5-year survival for European centers. Dr. Takahashi answers questions about the many factors contributing to these variances.

Follow along in the December issue at www.jhltonline.org/current, or, if you're an ISHLT member, log in at ishlt.org/journal-of-heart-lung-transplantation. Don't already get the Journal and want to read along? Join the International Society of Heart and Lung Transplantation at www.ishlt.org for a free subscription, or subscribe today at www.jhltonline.org.

This episode of JHLT: The Podcast, but not the studies within, is sponsored by Enzyvant.