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Background: Cardiac allograft vasculopathy (CAV) leads to impaired myocardial blood flow (MBF), increasing the risk of cardiovascular death or retransplant among heart transplantation (HT) recipients. Data on elevation in donor-derived cell-free DNA (dd-cfDNA) and CAV in the absence of rejection are mixed. We sought to test the hypothesis that CAV with reduced MBF (RMBF) is associated with elevated dd-cfDNA., Methods: A retrospective review was conducted on HT recipients at a high-volume center who underwent dd-cfDNA testing between September 2019 and November 2022. Inclusion criteria included undergoing CAV screening with cardiac positron emission tomography scans and coronary angiograms. Patients were grouped by the presence of angiographic CAV diagnosis and MBF reserve evaluated through cardiac positron emission tomography. The latter was subdivided into normal MBF or RMBF, with RMBF defined as an MBF reserve ≤2. Elevated dd-cfDNA was defined as ≥0.12%., Results: Two hundred fifty-six HT recipients were included (median age, 55 years; 27.6% female; median, 8 years [interquartile range (IQR), 5-14] post-HT). Ischemic etiology of heart failure was more prevalent in the RMBF group (36%) compared with the normal MBF group (20%; P =0.02). The prevalence and magnitude of a positive dd-cfDNA test with angiographic CAV (29%; median, 0.26% [IQR, 0.15%-0.62%]) were not significantly different from those without CAV (30%; P =0.94; median, 0.31% [IQR, 0.17%-0.71%]; P =0.38). However, RMBF patients exhibited significantly higher dd-cfDNA prevalence and levels (51%; median, 0.81% [IQR, 0.48%-1.11%]) compared with normal MBF patients (27%; P <0.001; median, 0.25% [IQR, 0.15%-0.52%]; P <0.001)., Conclusions: HT recipients with angiographic CAV had similar dd-cfDNA levels and rates as those without. Notably, dd-cfDNA levels and rates were significantly elevated in patients with RMBF assessed by positron emission tomography compared with those with normal MBF.

Competing Interests: Declarations of Competing Interest All authors declare that they have no conflicts of interest.

Background: Cardiac hybrid positron emission tomography/computed tomography (PET/CT) has become a valid screening modality for cardiac allograft vasculopathy (CAV) following heart transplantation (HT). Visually estimated coronary artery calcium (VECAC) can be quantified from CT images obtained as part of PET/CT and has been shown to be associated with adverse cardiovascular outcomes in coronary artery disease. We investigated the prognostic value of VECAC following HT., Methods: A retrospective analysis of 430 consecutive adult HT patients who underwent 13 N-ammonia cardiac PET/CT from 2016 to 2019 with follow-up through October 15, 2022, was performed. VECAC categories included: VECAC 0, VECAC 1-9, VECAC 10-99, and VECAC 100+. The association between VECAC categories and outcomes was assessed using univariable and multivariable proportional hazards regression. The primary outcome was death/retransplantation., Results: The cohort was 73% male, 33% had diabetes, 67% had estimated glomerular filtration rate <60 ml/min, median age was 61 years, and median time since HT was 7.5 years. VECAC alone was insufficiently sensitive to screen for CAV. During a median follow-up of 4.2 years ninety patients experienced death or retransplantation. Compared with those with VECAC 0, patients VECAC 10-99 (HR 2.25, 95% CI 1.23-4.14, p = 0.009) and VECAC 100+ (HR 3.42, 95% CI 1.96-5.99, p < 0.001) experienced an increased risk of death/retransplantation. The association was similar for cardiovascular death and cardiovascular hospitalization. After adjusting for other predictors of death/retransplantation, VECAC 10-99 (VECAC 10-99: aHR 1.95, 95% CI 1.03-3.71 p = 0.04) and VECAC 100+ (VECAC 100+: aHR 2.33, 95% CI 1.17-4.63, p = 0.02) remained independently associated with death/retransplantation., Conclusions: VECAC is an independent prognostic marker of death/retransplantation following HT and merits inclusion as a part of post-HT surveillance PET/CT., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Heart failure (HF) is a leading cause of cardiovascular morbidity, mortality, and health care expenditure. Guideline-directed medical therapy and device-based therapy in HF are well established. However, the role of nonpharmacologic modalities to improve HF care remains underappreciated, is underused, and requires multimodal approaches to care. Diet, exercise and cardiac rehabilitation, sleep-disordered breathing, mood disorders, and substance use disorders are potential targets to reduce morbidity and improve function of patients with HF. Addressing these factors may improve symptoms and quality of life, reduce hospitalizations, and improve mortality in heart failure. This state-of-the-art review discusses dietary interventions, exercise programs, and the management of sleep-disordered breathing, mood disorders, and substance use in individuals with heart failure. The authors review the latest data and provide optimal lifestyle recommendations and recommended prescriptions for nonpharmacologic therapies., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. All rights reserved.)

Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). Prior studies identified distinct CAV trajectories in the early post-HT period with unique predictors, but the evolution of CAV in later periods is not well-described. This study assessed the prevalence of late CAV progression and associated risk factors in HT recipients with ISHLT CAV 0/1 at 10 years post-HT. Consecutive adult patients who underwent HT from January 2000 to December 2008 were evaluated and grouped by CAV trajectories into progressors (developed ISHLT CAV 2/3) or nonprogressors (remained ISHLT CAV 0/1). A total of 130 patients were included with a median age at angiography of 61.7 years and a median follow-up time of 4.8 years. 8.5% progressed to CAV 2/3, while the remaining 91.5% were nonprogressors. Progression was not associated with death or retransplantation (27.3% [progressor] vs. 21.0% [nonprogressor], p = 0.70). These data may inform shared decision-making about late CAV screening., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Donor-derived cell-free DNA (dd-cfDNA) has emerged as a reliable, noninvasive method for the surveillance of allograft rejection in heart transplantation (HT) patients, but its utility in multi-organ transplants (MOT) is unknown. We describe our experience using dd-cfDNA in simultaneous MOT recipients., Methods: A single-center retrospective review of all HT recipients between 2018 and 2022 that had at least one measurement of dd-cfDNA collected. Patients who had simultaneous MOT were identified and included in this study. Levels of dd-cfDNA were paired with endomyocardial biopsies (EMB) performed within 1 month of blood testing if available. Acute cellular rejection (ACR) was defined as ISHLT (International Society for Heart and Lung Transplantation) grade ≥ 2R. and antibody-mediated rejection (AMR) was defined as pAMR grade > 0. The within-patient variability score of the dd-cfDNA was calculated by the variance/average., Results: The study included 25 multiorgan transplant recipients: 13 heart-kidney (H-K), 8 heart-liver (H-Li), and 4 heart-lung (H-Lu). The median age was 55 years, 44% were female; the median time from HT until the first dd-cfDNA measurement was 4.5 months (IQR 2, 10.5). The median dd-cfDNA level was 0.18% (IQR 0.15%, 0.27%) for H-K, 1.15% (IQR 0.77%, 2.33%) for H-Li, and 0.69% (IQR 0.62%, 1.07%) for H-Lu patients (p < 0.001). Prevalence of positive dd-cfDNA tests (threshold of 0.20%) were 42.2%, 97.3%, and 92.3% in the H-K, H-Li, and H-Lu groups, respectively. The within-patient variability score was highest in the H-Li group (median of 0.45 [IQR 0.29, 0.94]) and lowest in the H-K group (median of 0.09 [IQR 0.06, 0.12]); p = 0.002. No evidence of cardiac ACR or AMR was found. Three patients experienced renal allograft ACR and/or AMR, two patients experienced rejection of the liver allograft, and one patient experienced an episode of AMR-mediated lung rejection. One person in the H-K group experienced an episode of cardiac allograft dysfunction that was not associated with biopsy-confirmed rejection., Conclusion: Dd-cfDNA is chronically elevated in most MOT recipients. There is a high degree of within-patient variability in levels (particularly for H-Li and H-Lu recipients), which may limit the utility of this assay in monitoring MOT recipients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Women continue to remain under-represented in academic publishing in the field of cardiology. Some evidence suggests that double-blind peer reviews may mitigate the impact of gender bias. In July 2021, the Journal of Cardiac Failure implemented a process for the conduct of double-blind reviews after previously using single-blind reviews, with the aim of improving author diversity. The purpose of the current study was to examine the association between changes in authorship characteristics and implementation of double-blind reviews., Methods: Manuscripts were stratified into 3 Eras: March-September 2021 (Era 1: prior to double-blind reviews); March-September 2022 (Era 2); and March-September 2023 (Era 3). All article types except invited editorials were included. Data were abstracted, including names, genders, ranks, and disciplines of the first and senior authors., Results: A total of 310 manuscripts were included in the analysis. The proportion of women first authors increased from 24% in Era 1 to 34% in Era 2 to 39% in Era 3, while the percentage of women authors serving in a senior authorship role remained fairly stable over time-around 21%-22%. Even after adjusting for region, article type, first-author discipline, and last-author gender, there was an increase in female first authors over time (P = 0.015). Manuscripts with a female senior author were significantly more likely to have a female first author., Conclusions: Our findings suggest that double-blind peer review may contribute to increased gender diversity of first authors and may highlight areas for future improvement by the Journal and academic publishing in general., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: More women of childbearing age are surviving after heart transplantation (HT), many of whom have a desire to become pregnant. Limited data exist evaluating patients' perspectives, receipt of counseling, and knowledge surrounding contraception, pregnancy, breastfeeding, and medication safety after HT., Methods: We conducted a voluntary, confidential, web-based cross-sectional survey of women who were childbearing age (defined as 18-45 years) at the time of HT. Transplants occurred between January 2005 and January 2020. Surveys were conducted across 6 high-volume HT centers in the United States., Results: There were 64 responses from women who were of childbearing age at the time of HT. Twenty-five women (39.1%) were pregnant before HT, and 6 (9.4%) women reported at least 1 pregnancy post-transplant. Fifty-three percent (n=34) reported they did not receive enough information on post-HT pregnancy before listing for HT, and 26% (n=16) did not discuss their ability to become pregnant with their care team before proceeding with HT. Following HT, 44% (n=28) still felt that they had not received enough information regarding pregnancy. The majority of women (n=49, 77%) had discussed contraception to prevent unplanned pregnancy with their transplant team. Twenty percent (n=13) reported that pregnancy was never safe after transplantation based on the information they had received from their transplant providers., Conclusions: Many women feel they are not receiving adequate counseling with regard to posttransplant reproductive health. This survey highlights an opportunity to improve both provider education and patient communication to better support women with HT desiring posttransplant pregnancy., Competing Interests: None.

Online education materials are widely used by patients and caregivers to understand the management of complex chronic diseases such as heart failure (HF). Organizations such as the American Medical Association and National Institutes of Health recommend that materials be written at a 6th-grade reading level. The current study examined the readability and accessibility of online education materials for patients with HF. Whole page texts from each included website were entered into an online readability calculator. Five validated readability indices (Flesch-Kincaid Grade Level, Flesch Reading Ease Scale, Gunning Fog Index, Coleman-Liau Index, and Simple Measure of Gobbledygook (SMOG Index)) were used to evaluate each source. Websites were categorized by source (government, public and private). The availability of audiovisual accessibility features and content in non-English languages were assessed for each website. Of the 36 online resources analyzed, the median readability level was 9th-10th grade according to the Flesch-Kincaid Grade Level and college level, according to the Flesch Reading Ease Scale. The Gunning Fog Index and Coleman-Liau Index both showed median readability scores corresponding to a 12th grade reading level, whereas the SMOG Index showed a median score corresponding to that of the 9th grade. Only 10 websites (28%) offered information in languages other than English, and none provided comprehensive accessibility features for users with disabilities. Common online educational materials for patients with HF are characterized by higher readability levels than those recommended by the National Institutes of Health and the American Medical Association, and there were limited multilingual and accessibility options, potentially limiting the accessibility of resources to patients and caregivers., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Since the 2018 allocation system change in heart transplantation (HT), ischemic times have increased, which may be associated with peri-operative and post-operative complications. This study aimed to compare ischemia reperfusion injury (IRI) in hearts preserved using ice-cold storage (ICS) and the Paragonix SherpaPak TM Cardiac Transport System (CTS)., Methods: From January 2021 to June 2022, consecutive endomyocardial biopsies from 90 HT recipients were analyzed by a cardiac pathologist in a single-blinded manner: 33 ICS and 57 CTS. Endomyocardial biopsies were performed at three-time intervals post-HT, and the severity of IRI manifesting histologically as coagulative myocyte necrosis (CMN) was evaluated, along with graft rejection and graft function., Results: The incidence of IRI at weeks 1, 4, and 8 post-HT were similar between the ICS and CTS groups. There was a 59.3% statistically significant reduction in CMN from week 1 to 4 with CTS, but not with ICS. By week 8, there were significant reductions in CMN in both groups. Only 1 out of 33 (3%) patients in the ICS group had an ischemic time >240 mins, compared to 10 out of 52 (19%) patients in the CTS group. During the follow-up period of 8 weeks to 12 months, there were no significant differences in rejection rates, formation of de novo donor-specific antibodies and overall survival between the groups., Conclusion: The CTS preservation system had similar rates of IRI and clinical outcomes compared to ICS despite longer overall ischemic times. There is significantly more recovery of IRI in the early post operative period with CTS. This study supports CTS as a viable option for preservation from remote locations, expanding the donor pool., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Inadequate inclusion in clinical trial enrollment may contribute to health inequities by evaluating interventions in cohorts that do not fully represent target populations., Objectives: The aim of this study was to determine if characteristics of patients with heart failure (HF) enrolled in a pivotal trial are associated with who receives an intervention after approval., Methods: Demographics from 2,017,107 Medicare patients hospitalized for HF were compared with those of the first 10,631 Medicare beneficiaries who received implantable pulmonary artery pressure sensors. Characteristics of the population studied in the pivotal CHAMPION (CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients) clinical trial (n = 550) were compared with those of both groups. All demographic data were analyzed nationally and in 4 U.S. regions., Results: The Medicare HF cohort included 80.9% White, 13.3% African American, 1.9% Hispanic, 1.3% Asian, and 51.5% female patients. Medicare patients <65 years of age were more likely to be African American (33%) and male (58%), whereas older patients were mostly White (84%) and female (53%). Forty-one percent of U.S. HF hospitalizations occurred in the South; demographic characteristics varied significantly across all U.S. regions. The CHAMPION trial adequately represented African Americans (23% overall, 35% <65 years of age), Hispanic Americans (2%), and Asian Americans (1%) but underrepresented women (27%). The trial's population characteristics were similar to those of the first patients who received pulmonary artery sensors (82% White, 13% African American, 1% Asian, 1% Hispanic, and 29% female)., Conclusions: Demographics of Centers for Medicare and Medicaid Services beneficiaries hospitalized with HF vary regionally and by age, which should be considered when defining "adequate" representation in clinical studies. Enrollment diversity in clinical trials may affect who receives early application of recently approved innovations., Competing Interests: Funding Support and Author Disclosures Abbott provided resources for access and analyses of CMS claims data and demographic information from the CHAMPION trial. Dr Adamson is an employee of Abbott. Dr Echols is a consultant to Abbott. Dr DeFilippis serves on a clinical trial committee for Abiomed. Dr Morris has received research funding from the Agency for Healthcare Research and Quality (HS026081), the American Heart Association, Google, and Merck; and has received consulting fees from Abbott, Acorai, Boehringer Ingelheim, Eli Lilly, Cytokinetics, Edwards Lifesciences, Ionis, Merck, and Regeneron. Dr Bennett has received consulting fees and speaker honoraria from Abbott. Dr Abraham has received consulting fees from Abbott Vascular, AquaPass, Boehringer Ingelheim, Impulse Dynamics, Sensible Medical Innovations, V-Wave, and Zoll Respicardia. Dr Lindenfeld has received consulting and/or research support from Abbott, AstraZeneca, Boehringer Ingelheim, Boston Scientific, CVRx, Edwards Lifesciences, Impulse Dynamics, Merck, Medtronic, V-Wave, Vifor, and Volumetrix. Dr Teerlink has received research support from 3ive Labs, AstraZeneca, Bayer, Boehringer Ingelheim, Cardurion, Cytokinetics, EBR Systems, Edwards Lifesciences, Impulse Dynamics, Kaiser Permanente, LivaNova, Medtronic, Myovant Sciences, the Patient-Centered Outcomes Research Institute, RECARDIO, and V-Wave; and is a consultant for 3ive Labs, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, CorHepta, Cytokinetics, Daiichi-Sankyo, EBR Systems, Edwards Lifesciences, Eli Lilly Impulse Dynamics, JuvLabs, Kaiser Permanente, LivaNova, Medtronic, Myovant Sciences, Novartis, the Patient-Centered Outcomes Research Institute, Pfizer, ReCor Medical, Regeneron, Reprieve, Tectonic, V-Wave, Verily, ViCardia, and Windtree Therapeutics. Dr O’Connor has received research funding from Merck; and has received consulting fees from Bayer and Dey. Dr Connolly is an employee of Abbott. Dr Li is an employee of Abbott. Dr. Vaduganathan has received research grant support from, served on advisory boards for, or has had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer, Baxter Healthcare, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and has participated on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer, Occlutech, and Impulse Dynamics. Dr Batchelor has received consulting fees from Boston Scientific, Medtronic, Edwards Lifesciences, V-Wave, Chiesi, Abbott, and Idorsia; and has received research support from Abbott and Boston Scientific. Dr McCants has received consulting fees and speaker honoraria from Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The use of glucagon-like-peptide 1 receptor agonists (GLP1-RA) has dramatically increased over the past 5 years for diabetes mellitus type 2 (T2DM) and obesity. These comorbidities are prevalent in adult heart transplant (HT) recipients. However, there are limited data evaluating the efficacy of this drug class in this population. The aim of the current study was to describe cardiometabolic changes in HT recipients prescribed GLP1-RA at a large-volume transplant center., Methods: We retrospectively reviewed all adult HT recipients who received GLP1-RA after HT for a minimum of 1-month. Cardiometabolic parameters including body mass index (BMI), lipid panel, hemoglobin A1C, estimated glomerular filtration rate (eGFR), and NT-proBNP were compared prior to initiation of the drug and at most recent follow-up. We also evaluated for significant dose adjustments to immunosuppression after drug initiation and adverse effects leading to drug discontinuation., Results: Seventy-four patients were included (28% female, 53% White, 20% Hispanic) and followed for a median of 383 days [IQR 209, 613] on a GLP1-RA. The majority of patients (n = 56, 76%) were prescribed semaglutide. The most common indication for prescription was T2DM alone (n = 33, 45%), followed by combined T2DM and obesity (n = 26, 35%). At most recent follow-up, mean BMI decreased from 33.3 to 31.5 kg/m 2 (p < 0.0001), HbA1C from 7.3% to 6.7% (p = 0.005), LDL from 78.6 to 70.3 mg/dL (p = 0.018) and basal insulin daily dose from 32.6 to 24.8 units (p = 0.0002)., Conclusion: HT recipients prescribed GLP1-RA therapy showed improved glycemic control, weight loss, and cholesterol levels during the study follow-up period. GLP1-RA were well tolerated and were rarely associated with changes in immunosuppression dosing., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Noninvasive methods for surveillance of acute rejection are increasingly used in heart transplantation (HT), including donor-derived cell-free DNA (dd-cfDNA). As other cardiac biomarkers differ by sex, we hypothesized that there may be sex-specific differences in the performance of dd-cfDNA for the detection of acute rejection. The purpose of the current study was to examine patterns of dd-cfDNA seen in quiescence and acute rejection in male and female transplant recipients., Methods: Patients enrolled in the Genomic Research Alliance for Transplantation who were ≥18 years at the time of HT were included. Rejection was defined by endomyocardial biopsy with acute cellular rejection (ACR) grade ≥2R and/or antibody-mediated rejection ≥ pAMR 1. dd-cfDNA was quantitated using shotgun sequencing. Median dd-cfDNA levels were compared between sexes during quiescence and rejection. The performance of dd-cfDNA by sex was assessed using area under the receiver operator characteristic (AUROC) curve. Allograft injury was defined as dd-cfDNA ≥0.25%., Results: One hundred fifty-one unique patients (49 female, 32%) were included in the analysis with 1,119 available dd-cfDNA measurements. Baseline characteristics including demographics and comorbidities were not significantly different between sexes. During quiescence, there were no significant sex differences in median dd-cfDNA level (0.04% [IQR 0.00, 0.16] in females vs 0.03% [IQR 0.00, 0.12] in males, p = 0.22). There were no significant sex differences in median dd-cfDNA for ACR (0.33% [0.21, 0.36] in females vs 0.32% [0.21, 1.10] in males, p = 0.57). Overall, median dd-cfDNA levels were higher in antibody-mediated rejection (AMR) than ACR but did not significantly differ by sex (0.50% [IQR 0.18, 0.82] in females vs 0.63% [IQR 0.32, 1.95] in males, p = 0.51). Elevated dd-cfDNA detected ACR/AMR with an AUROC of 0.83 in females and 0.89 in males, p-value for comparison = 0.16., Conclusions: There were no significant sex differences in dd-cfDNA levels during quiescence and rejection. Performance characteristics were similar, suggesting similar diagnostic thresholds can be used in men and women for rejection surveillance., (Copyright © 2024 International Society for the Heart and Lung Transplantation. All rights reserved.)

Objectives: To evaluate the clinical implications of adjunctive molecular gene expression analysis (MMDx ) of biopsy specimens in heart transplant (HT ) recipients with suspected rejection., Introduction: Histopathological evaluation remains the standard method for rejection diagnosis in HT. However, the wide interobserver variability combined with a relatively common incidence of "biopsy-negative" rejection has raised concerns about the likelihood of false-negative results. MMDx, which uses gene expression to detect early signs of rejection, is a promising test to further refine the assessment of HT rejection., Methods: Single-center prospective study of 418 consecutive for-cause endomyocardial biopsies performed between November 2022 and May 2024. Each biopsy was graded based on histology and assessed for rejection patterns using MMDx. MMDx results were deemed positive if borderline or definitive rejection was present. The impact of MMDx results on clinical management was evaluated. Primary outcomes were 1-year survival and graft dysfunction following MMDx-guided clinical management. Secondary outcomes included changes in donor-specific antibodies, MMDx gene transcripts, and donor-derived cell-free DNA (dd-cfDNA) levels., Results: We analyzed 418 molecular samples from 237 unique patients. Histology identified rejection in 32 cases (7.7%), while MMDx identified rejection in 95 cases (22.7%). Notably, in 79 of the 95 cases where MMDx identified rejection, histology results were negative, with the majority of these cases being antibody-mediated rejection (62.1%). Samples with rejection on MMDx were more likely to show a combined elevation of dd-cfDNA and peripheral blood gene expression profiling than those with borderline or negative MMDx results (36.7% vs 28.0% vs 10.3%; p<0.001). MMDx results led to the implementation of specific antirejection protocols or changes in immunosuppression in 20.4% of cases, and in 73.4% of cases where histology was negative and MMDx showed rejection. 1-year survival was better in the positive MMDx group where clinical management was guided by MMDx results (87.0% vs 78.6%; log rank p=0.0017)., Conclusions: In our cohort, MMDx results more frequently indicated rejection than histology, often leading to the initiation of antirejection treatment. Intervention guided by positive MMDx results was associated with improved outcomes.

Financial considerations continue to impact access to heart transplantation. Transplant recipients face various costs, including, but not limited to, the index hospitalization, immunosuppressive medications, and lodging and travel to appointments. In this study, we sought to describe the state of crowdfunding for individuals being evaluated for heart transplantation. Using the search term heart transplant, 1000 GoFundMe campaigns were reviewed. After exclusions, 634 (63.4%) campaigns were included. Most campaigns were in support of white individuals (57.8%), males (63.1%) and adults (76.7%). Approximately 15% of campaigns had not raised any funds. The remaining campaigns fundraised a median of $53.24 dollars per day. Of the patients, 44% were admitted at the time of the fundraising. Within the campaigns in the United States, the greatest proportions were in the Southeast United States in non-Medicaid expansion states. These findings highlight the significant financial toxicities associated with heart transplantation and the need for advocacy at the governmental and payer levels to improve equitable access and coverage for all., Competing Interests: Disclosures EMD and JL are on the Board of Directors for The Equity in Heart Transplant Project. NI is the founder and executive director of The Equity in Heart Transplant Project. All remaining authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The numbers of women of child-bearing age undergoing heart transplantation (HT) and female pediatric HT recipients surviving to child-bearing age have increased, along with improvements in post-transplant survival. Data regarding life expectancy and comorbidities in reproductive-aged female HT recipients are needed to inform shared decision-making at the time of preconception counseling., Methods: The International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant Registry was investigated for HT recipients between January 1, 2000 and June 30, 2017. Women of childbearing age were defined as those aged 15-45 years, either at transplant, or at the respective post-transplant follow-up. Characteristics and outcomes of female recipients of childbearing age at transplant, 5-, 10-, and 15-year follow-up were compared to females > 45 years of age, males 15-45 years and males > 45 years of age at the corresponding time intervals. Outcomes included survival, development of diabetes (DM), severe renal dysfunction (CKD), and cardiac allograft vasculopathy (CAV)., Results: During the study period, 71,585 HT recipients were included: 24% (n = 17,194) were female and 9.2% (n = 6602) were of childbearing age at HT. A pre-transplant diagnosis of peripartum cardiomyopathy was associated with significantly worse post-transplant survival, a finding that remained independent of panel reactive antibody levels. The presence of pre-transplant DM and/or severe CKD was significantly associated with lower survival as were the presence of CAV, DM, and CKD post-HT., Conclusion: Knowledge of the impact of pre-existing comorbidities and complications post-HT on survival are important for risk stratification for preconception counseling post-HT., (Copyright © 2024 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

This review serves to compare contemporary clinical practice recommendations for the management of heart failure (HF), as codified in the 2021 European Society of Cardiology (ESC) guideline, the 2022 American College of Cardiology (ACC)/American Heart Association (AHA)/Heart Failure Society of America (HFSA) guideline, and the 2023 focused update of the 2021 ESC document. Overall, these guidelines aim to solidify significant advances throughout the HF continuum since the publication of previous full guideline iterations (2013 and 2016 for the ACC/AHA and ESC, respectively). All guidelines provide new recommendations for an increasingly complex landscape of HF care, with focus on primary HF prevention, HF stages, rapid initiation and optimization of evidence-based pharmacotherapies, overlapping cardiac and noncardiac comorbidities, device-based therapies, and management pathways for special groups of patients, including those with cardiac amyloidosis. Importantly, the ACC/AHA/HFSA document features special emphasis on HF risk prediction and screening, cost/value, social determinants of health, and health care disparities. The review discusses major similarities and differences between these recent guidelines and guideline updates, as well as their potential downstream implications for clinical care., Competing Interests: Funding Support and Author Disclosures Dr DeFilippis serves on a clinical trial committee for Abiomed and has had speaker engagements with AstraZeneca. Dr Riello has served as a consultant for Alexion AstraZeneca, Boehringer Ingelheim, Janssen, Johnson & Johnson, PhaseBio, and Portola. Dr Bozkurt has received personal fees from Vifor for serving on the steering committee for the Care HF Trial; has received personal fees from Amgen, AstraZeneca, and Baxter for serving on advisory committees or for consulting outside the submitted work; has received consulting fees from Bristol Myers Squibb, scPharmaceuticals, Baxter Healthcare Corporation, Sanofi Aventis, Relypsa, and Amgen; has served on the clinical event committee for the GUIDE HF Trial sponsored by Abbott Vascular; and has served on the data safety monitoring committee of the ANTHEM trial sponsored by LivaNova. Dr Vaduganathan has received research grant support from, has served on advisory boards of, or has had speaker engagements with American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Bristol Myers Squibb, Chiesi, Cytokinetics, Lexicon Pharmaceuticals, Merck, Novartis, Novo Nordisk, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and has participated on clinical trial committees for studies sponsored by AstraZeneca, Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Among patients with advanced heart failure (HF), treatment with a left ventricular assist device (LVAD) improves health-related quality of life (HRQOL). We investigated the association between psychosocial risk factors, HRQOL and outcomes after LVAD implantation., Methods: A retrospective cohort (n = 9832) of adults aged ≥ 19 years who received durable LVADs between 2008 and 2017 was identified by using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). Patients were considered to have psychosocial risk factors if ≥ 1 of the following were present: (1) substance abuse; (2) limited social support; (3) limited cognitive understanding; (4) repeated nonadherence; and (5) major psychiatric disease. Multivariable logistic and linear regression models were used to evaluate the association between psychosocial risk factors and change in Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 scores from baseline to 1 year, persistently poor HRQOL (KCCQ-12 score < 45 at baseline and 1 year), and 1-year rehospitalization., Results: Among the final analytic cohort, 2024 (20.6%) patients had ≥ 1 psychosocial risk factors. Psychosocial risk factors were associated with a smaller improvement in KCCQ-12 scores from baseline to 1 year (mean ± SD, 29.1 ± 25.9 vs 32.6 ± 26.1; P = 0.015) for a difference of -3.51 (95% confidence interval [CI]: -5.88 to -1.13). Psychosocial risk factors were associated with persistently poor HRQOL (adjusted odds ratio [aOR] 1.35, 95% confidence interval [CI] 1.04-1.74), and 1-year all-cause readmission (adjusted hazard ratio [aHR] 1.11, 95% CI 1.05-1.18). Limited social support, major psychiatric disorder and repeated nonadherence were associated with persistently poor HRQOL, while major psychiatric disorder was associated with 1-year rehospitalization., Conclusion: The presence of psychosocial risk factors is associated with lower KCCQ-12 scores and higher risk for readmission at 1 year after LVAD implantation. These associations are statistically significant, but further research is needed to determine whether these differences are clinically meaningful., Competing Interests: Disclosures JW is supported by funding from the GA CTSA (UL1TR002378, TL1TR002382) and the National Heart, Lung and Blood Institute of the National Institutes of Health under award number 5T32HL007745. AAM is supported by funding from the American Heart Association and the Agency for Health Research and Quality (HS026081) and reports consulting fees or honoraria from Abbott, Acorai, BI Lilly, Cytokinetics, Edwards Lifesciences, Ionis, Merck and Regeneron. AKO is supported by funding from the American Heart Association. KB is supported by funding from the National Heart, Lung, and Blood Institute (NHLBI)K01HL142848, R01HL159216, R01HL160734 and funding from the Health Resources and Services Administration of the U.S. Department of Health and Human Services. All other authors report no disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: There are limited data evaluating the success of a structured transition plan specifically for pediatric heart transplant (HT) recipients following their transfer of care to an adult specialist. We sought to identify risk factors for poor adherence, graft failure, and mortality following the transfer of care to adult HT care teams., Methods: We retrospectively reviewed all patients who underwent transition from the pediatric to adult HT program at our center between January 2011 and June 2021. Demographic characteristics, comorbid conditions, and psychosocial history were collected at the time of HT, the time of transition, and the most recent follow-up. Adverse events including mortality, graft rejection, infection, and renal function were also captured before and after the transition., Results: Seventy-two patients were identified (54.1% male, 54.2% Caucasian). Mean age at the time of transition was 23 years after a median of 11.6 years in the pediatric program. The use of calcineurin inhibitors was associated with reduced mortality (HR .04, 95% CI .0-.6, p = .015), while prior psychiatric hospitalization (HR 45.3, 95% CI, 6.144-333.9, p = .0001) was associated with increased mortality following transition. Medication nonadherence and young age at the time of transition were markers for high-risk individuals prior to the transition of care., Conclusions: Transition of HT recipients from a pediatric program to an adult program occurs during a vulnerable time of emerging adulthood, and we have identified risk factors for mortality following transition. Development of a formalized transition plan with a large multidisciplinary team with focused attention on high-risk patients, including those with psychiatric comorbidities, may favorably influence outcomes., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Belatacept (BTC), a fusion protein, selectively inhibits T-cell co-stimulation by binding to the CD80 and CD86 receptors on antigen-presenting cells (APCs) and has been used as immunosuppression in adult renal transplant recipients. However, data regarding its use in heart transplant (HT) recipients are limited. This retrospective cohort study aimed to delineate BTC's application in HT, focusing on efficacy, safety, and associated complications at a high-volume HT center., Methods: A retrospective cohort study was conducted of patients who underwent HT between January 2017 and December 2021 and subsequently received BTC as part of their immunosuppressive regimen. Twenty-one HT recipients were identified. Baseline characteristics, history of rejection, and indication for BTC use were collected. Outcomes included renal function, graft function, allograft rejection and mortality. Follow-up data were collected through December 2023., Results: Among 776 patients monitored from January 2017 to December 2021 21 (2.7%) received BTC treatment. Average age at transplantation was 53 years (± 12 years), and 38% were women. BTC administration began, on average, 689 [483, 1830] days post-HT. The primary indications for BTC were elevated pre-formed donor-specific antibodies in highly sensitized patients (66.6%) and renal sparing (23.8%), in conjunction with reduced calcineurin inhibitor dosage. Only one (4.8%) patient encountered rejection within a year of starting BTC. Graft function by echocardiography remained stable at 6 and 12 months posttreatment. An improvement was observed in serum creatinine levels (76.2% of patients), decreasing from a median of 1.58 to 1.45 (IQR [1.0-2.1] to [1.1-1.9]) over 12 months (p = .054). eGFR improved at 3 and 6 months compared with 3 months pre- BTC levels; however, this was not statistically significant (p = .24). Treatment discontinuation occurred in seven patients (33.3%) of whom four (19%) were switched back to full dose CNI. Infections occurred in 11 patients (52.4%), leading to BTC discontinuation in 4 patients (19%)., Conclusion: In this cohort, BTC therapy was used as alternative immunosuppression for management of highly sensitized patients or for renal sparing. BTC therapy when combined with CNI dose reduction resulted in stabilization in renal function as measured through renal surrogate markers, which did not, however, reach statistical significance. Patients on BTC maintained a low rejection rate and preserved graft function. Infections were common during BTC therapy and were associated with medication pause/discontinuation in 19% of patients. Further randomized studies are needed to assess the efficacy and safety of BTC in HT recipients., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Among heart transplant (HT) recipients who develop advanced graft dysfunction, cardiac re-transplantation may be considered. A smaller subset of patients will experience failure of their second allograft and undergo repeat re-transplantation. Outcomes among these individuals are not well-described., Methods: Adult and pediatric patients in the United Network for Organ Sharing (UNOS) registry who received HT between January 1, 1990 and December 31, 2020 were included., Results: Between 1990 and 2020, 90 individuals received a third HT and three underwent a fourth HT. Recipients were younger than those undergoing primary HT (mean age 32 years). Third HT was associated with significantly higher unadjusted rates of 1-year mortality (18% for third HT vs. 13% for second HT vs. 9% for primary HT, p < .001) and 10-year mortality (59% for third HT vs. 42% for second HT vs. 37% for primary HT, p < .001). Mortality was highest amongst recipients aged >60 years and those re-transplanted for acute graft failure. Long-term rates of CAV, rejection, chronic dialysis, and hospitalization for infection were also higher., Conclusions: Third HT is associated with higher morbidity and mortality than primary HT. Further consensus is needed regarding appropriate organ stewardship for this unique subgroup., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Monitoring for graft rejection is a fundamental tenet of post-transplant follow-up. In heart transplantation (HT) in particular, rejection has been traditionally assessed with endomyocardial biopsy (EMB). EMB has potential complications and noted limitations, including interobserver variability in interpretation. Additional tests, such as basic cardiac biomarkers, cardiac imaging, gene expression profiling (GEP) scores, donor-derived cell-free DNA (dd-cfDNA) and the novel molecular microscope diagnostic system (MMDx) have become critical tools in rejection surveillance beyond standard EMB., Methods: This paper describes an illustrative case followed by a review of MMDx within the context of other noninvasive screening modalities for rejection., Conclusions: We suggest MMDx be used to assist with early detection of rejection in cases of discordance between EMB and other noninvasive studies., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose of Review: The goal of this review was to summarize contemporary evidence surrounding sex differences in heart transplantation (HT)., Recent Findings: Women have steadily comprised approximately 25% of waitlist candidates and HT recipients. This disparity is likely multifactorial with possible explanations including barriers in referral to advanced heart failure providers, implicit bias, and concerns surrounding sensitization. Women continue to experience higher waitlist mortality at the highest priority tiers. After HT, there are differences in post-transplant complications and outcomes. Future areas of study should include sex differences in noninvasive surveillance, renal outcomes after transplantation, and patient-reported outcomes. There are important sex-specific considerations that impact candidate selection, donor matching, waitlist and post-transplant outcomes. Concerted efforts are needed to improve referral patterns to ensure transplantation is allocated equally., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Guideline-directed medical therapy (GDMT) is recommended before mitral valve transcatheter edge-to-edge repair (MTEER) in patients with heart failure (HF) and severe functional mitral regurgitation (FMR). Whether MTEER is being performed on the background of optimal GDMT in clinical practice is unknown., Methods: Patients with left ventricular ejection fraction (LVEF) < 50% who underwent MTEER for FMR from 23 July 2019 to 31 March 2022 in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were identified. Pre-procedure GDMT utilization was assessed. Cox proportional hazards models were constructed to evaluate associations between pre-MTEER therapy (no/single, double, or triple therapy) and risk of 1-year mortality or HF hospitalization (HFH)., Results: Among 4199 patients across 449 sites, beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, mineralocorticoid receptor antagonists, and angiotensin receptor-neprilysin inhibitors were used in 85.1%, 44.4%, 28.6%, and 19.9% before MTEER, respectively. Triple therapy was prescribed for 19.2%, double therapy for 38.2%, single therapy for 36.0%, and 6.5% were on no GDMT. Significant centre-level variation in the proportion of patients on pre-intervention triple therapy was observed (0%-61%; adjusted median odds ratio 1.48 [95% confidence interval (CI) 1.25-3.88]; P < .001). In patients eligible for 1-year follow-up (n = 2014; 341 sites), the composite rate of 1-year mortality or HFH was lowest in patients prescribed triple therapy (23.0%) compared with double (24.8%), single (35.7%), and no (41.1%) therapy (P < .01 comparing across groups). Associations persisted after accounting for relevant clinical characteristics, with lower risk in patients prescribed triple therapy [adjusted hazard ratio (aHR) 0.73, 95% CI .55-.97] and double therapy (aHR 0.69, 95% CI .56-.86) before MTEER compared with no/single therapy., Conclusions: Under one-fifth of patients with LVEF <50% who underwent MTEER for FMR in this US nationwide registry were prescribed comprehensive GDMT, with substantial variation across sites. Compared with no/single therapy, triple and double therapy before MTEER were independently associated with reduced risk of mortality or HFH 1 year after intervention., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The 2018 heart allocation policy sought to improve risk stratification and reduce waitlist mortality for the sickest patients. This study sought to evaluate changes in wait times for the highest priority patients since policy implementation. All adult single-organ transplant recipients were identified in the United Network for Organ Sharing registry from October 18, 2018, to July 8, 2022, and separated into 4 periods. Outcomes were compared by blood type and UNOS region. Over the study period, 897 of 9,143 patients were listed as status 1 with no significant change in median wait time by blood type or region. More patients were listed as status 2 (4,523/9,143), and each subsequent period postpolicy change was associated with a 4.2-day increase in mean status 2 waitlist time (95% confidence interval 3.0-5.5, p < 0.0001). Wait times were longest for candidates with blood type O and shortest for AB & A. Regional variations continued, however, wait time increased in every region over time., (Copyright © 2023 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The impact of heart transplant (HT) waitlist candidate sensitization on waitlist outcomes in the US is unknown., Methods: Adult waitlist outcomes in OPTN (October 2018-September 2022) by calculated panel reactive antibody (cPRA) were modeled to identify thresholds of clinical significance. The primary outcome was the rate of HT by cPRA category (low: 0-35, middle: >35-90, high: >90) assessed using multivariable competing risk analysis (compete: waitlist removal for death or clinical deterioration). The secondary outcome was waitlist removal for death or clinical deterioration., Results: The elevated cPRA categories were associated with lower rates of HT. Candidates in the middle (35-90) and high cPRA categories (>90) had an adjusted 24% lower rate (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.80-0.92) and 61% lower rate (HR 0.39 95% CI. 0.33-0.47) of HT than the lowest category, respectively. Waitlist candidates in the high cPRA category listed in the top acuity strata (Statuses 1, 2) had increased rates of delisting for death or deterioration compared to those in the low cPRA category (adjusted HR 2.9, 95% CI 1.5-5.5), however, elevated cPRA (middle, high) was not associated with an increased rate of death and delisting when the cohort was considered as a whole., Conclusions: Elevated cPRA was associated with reduced rates of HT across all waitlist acuity tiers. Among HT waitlist candidates listed at the top acuity strata, the high cPRA category was associated with increased rates of delisting due to death or deterioration. Elevated cPRA may require consideration for critically ill candidates under continuous allocation., (Published by Elsevier Inc.)

Background: Non-US citizens/non-US residents (NCNR) are a unique and growing population. Patterns of heart donation and heart transplantation (HT) within this subgroup have not been described fully. The purpose of this study was to evaluate the use of organs from NCNR donors and the characteristics and outcomes of NCNR HT recipients., Methods: All adult donors whose hearts were recovered for HT and all primary adult HT recipients from 2013 to 2020 were identified using the United Network for Organ Sharing. Donors and recipients were categorized as citizens, residents, or NCNR. NCNR were further categorized by reason for travel to the United States. Outcomes included mortality, infection, and rejection at 1-year after transplantation., Results: NCNR accounted for 0.4% (n = 77) of heart donors. Most NCNR donors identified as Hispanic (61%), were predominately recovered from the South and Southwest United States, and were less likely to express written documentation to be a donor compared with citizens and residents. NCNR accounted for 0.7% (n = 147) of all HT recipients. The majority identified as non-Hispanic White individuals (57.1%). Compared with citizens and residents, NCNR recipients seemed to be sicker, as evidenced by higher intra-aortic balloon pump use before HT and higher priority United Network for Organ Sharing status. Of NCNR recipients, 63% traveled to the United States for HT, predominately from Kuwait (29.9%) and Saudi Arabia (20%). At 1-year after transplant, there were no differences in mortality, infection, or rejection between the groups., Conclusions: A growing subgroup of NCNR travel from countries with low HT rates to the United States for HT. This finding highlights the need for strategies to improve equitable access to HT domestically and abroad., Competing Interests: Disclosures The authors have no relevant disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Heart failure and cardiomyopathy are significant contributors to pregnancy-related deaths, as maternal morbidity and mortality have been increasing over time. In this setting, the role of the multidisciplinary cardio-obstetrics team is crucial to optimizing maternal, obstetrical and fetal outcomes. Although peripartum cardiomyopathy is the most common cardiomyopathy experienced by pregnant individuals, the hemodynamic changes of pregnancy may unmask a pre-existing cardiomyopathy leading to clinical decompensation. Additionally, there are unique management considerations for women with pre-existing cardiomyopathy as well as for those women with advanced heart failure who may be on left ventricular assist device support or have undergone heart transplantation. The purpose of this review is to discuss: 1) preconception counseling; 2) risk stratification and management strategies for pregnant women extending to the postpartum "fourth trimester" with pre-existing heart failure or "pre-heart failure;" 3) the safety of heart failure medications during pregnancy and lactation; and 4) management of pregnancy for women on left ventricular assist device support or after heart transplantation., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Permanent pacemakers (PPMs) may be necessary in up to 10% of patients after heart transplantation (HT)., Objectives: The purpose of this study was to evaluate long-term outcomes and clinical courses of heart transplant recipients who received PPM., Methods: All patients who required PPM after bicaval HT at Columbia University between January 2005 and December 2021 were included. Cases were compared to matched heart transplant recipients by age, sex, and year of transplantation. Patient and device characteristics including complications and device interrogations were reviewed. Outcomes of re-transplantation or graft failure/death were compared between groups., Results: Of 1,082 heart transplant recipients, 41 (3.8%) received PPMs. The median time from transplantation to PPM was 118 days (IQR: 18-920 days). The most common indications were sinus node dysfunction (60%, n = 25) and atrioventricular (AV) nodal disease (41.5%, n = 17). Post-implantation complications included pocket hematoma (n = 3), lead under-sensing (n = 2), and pocket infection requiring explant (n = 1). Rates of death and re-transplantation at 10 years post-HT were similar between groups. In multivariable analysis, after adjustment for mechanical circulatory support, pretransplantation amiodarone use, donor ischemic time and age, only older donor age was associated with increased risk of PPM implantation (P = 0.03). There was a significant decrease in PPM placement after 2018 (1.2% vs 4.4%, P = 0.02), largely driven by a decline in early PPM placement. There were no differences in mortality or need for re-transplantation between groups., Conclusions: PPMs are implanted after HT for sinus and atrioventricular node dysfunctions with low incidence of device-related complications. Our study shows a decrease in PPM implantation after 2018, likely attributable to expectant management in the early postoperative period., Competing Interests: Funding Support and Author Disclosures Dr Wan has received grants from the National Institute of Health R01HL152236; and has been a consultant for Boston Scientific, Medtronic, Abbott, Sanofi, and Cardiologs. Dr Biviano has been a medical advisory board member for Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Women represent only about 25% of heart transplant recipients annually. Although the number of women living with advanced heart failure remains unknown, epidemiologic research suggests that more women should be receiving advanced heart failure therapies. Sex differences in risk factors, presentation, response to pharmacotherapy, and outcomes in heart failure have been well described. Yet, less is known about sex differences in heart transplant candidate selection, waitlist management, donor selection, perioperative considerations, and post-transplant management and outcomes. The purpose of this review was to summarize the existing published reports related to sex differences in heart transplantation, highlighting areas in which sex-based considerations are well described and supported by available evidence, and emphasizing topics that require further study., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease is the leading cause of pregnancy-related death in the United States. American Indian and Alaska Native individuals have some of the highest maternal death and morbidity rates. Data on the causes of cardiovascular disease-related death in American Indian and Alaska Native individuals are limited, and there are several challenges and opportunities to improve maternal cardiovascular health in this population. This scientific statement provides an overview of the current status of cardiovascular health among American Indian and Alaska Native birthing individuals and causes of maternal death and morbidity and describes a stepwise multidisciplinary framework for addressing cardiovascular disease and cerebrovascular disease during the preconception, pregnancy, and postpartum time frame. This scientific statement highlights the American Heart Association's factors for cardiovascular health assessment known collectively as Life's Essential 8 as they pertain to American Indian and Alaska Native birthing individuals. It summarizes the impact of substance use, adverse mental health conditions, and lifestyle and cardiovascular disease risk factors, as well as the cascading effects of institutional and structural racism and the historical trauma faced by American Indian and Alaska Native individuals. It recognizes the possible impact of systematic acts of colonization and dominance on their social determinants of health, ultimately translating into worse health care outcomes. It focuses on the underreporting of American Indian and Alaska Native disaggregated data in pregnancy and postpartum outcomes and the importance of engaging key stakeholders, designing culturally appropriate care, building trust among communities and health care professionals, and expanding the American Indian and Alaska Native workforce in biomedical research and health care settings to optimize the cardiovascular health of American Indian and Alaska Native birthing individuals.

Background: While sex differences in heart transplantation (HT) waitlist mortality have been previously described, waitlist and HT outcomes by sex of patients in the highest urgency strata (Status 1) since implementation of the 2018 allocation system change in the United States are unknown. We hypothesized that women listed as Status 1 may have worse outcomes due to adverse events on temporary mechanical circulatory support., Methods: The analysis included adult, single-organ HT waitlist candidates listed as Status 1 at any time while listed, after the HT allocation system change (from October 18, 2018 through March 31, 2022). The primary outcome was the rate of HT by sex, assessed using multivariable competing risk analysis where waitlist removal for death or clinical deterioration was the competing event. Post-HT survival by sex of waitlist candidates transplanted as a Status 1 was also compared., Results: Of 1120 Status 1 waitlist candidates (23.8% women), women had a lower rate of HT compared to men (adjusted hazard ratio, 0.74 [95% CI, 0.62-0.88]; P <0.001) and a higher rate of delisting for death or medical unsuitability (adjusted hazard ratio, 1.48 [95% CI, 1.05-2.09]; P =0.026). Calculated panel reactive antibody did not account for all the harm observed. Post-HT survival of Status 1 candidates by sex was similar (adjusted hazard ratio, 1.13 [95% CI, 0.62-2.06]; P =0.70)., Conclusions: Women have a lower rate of HT and higher rate of delisting for death or clinical deterioration at the highest urgent status, which appears to be mediated but not fully explained by calculated panel reactive antibody levels. Further investigation into the safety profile of temporary mechanical circulatory support devices in women is needed., Competing Interests: Disclosures Dr Cogswell reports being on the advisory boards of Abbott Labs and Medtronic and spousal employment at Medtronic. The other authors report no conflicts.

Background: The safety and efficacy of using COVID-19 positive donors in heart transplantation (HT) are increasingly relevant, but not well established. The present study evaluated the characteristics and utilization of such donors and associated post-HT outcomes., Methods: All adult (≥18 years old) potential donors and HT recipients in the United States from April 21, 2020 to March 31, 2022 were included. Donor COVID-19 status was defined by the presence (or absence) of any positive test within 21 days of organ recovery. Donor and recipient characteristics and post-HT outcomes, including a primary composite of death, graft failure, and re-transplantation, were compared by donor COVID-19 status., Results: Of 967 COVID-19(+) potential donors, 19.3% (n = 187) were used for HT compared to 26.7% (n = 6277) of COVID-19(-) donors (p < 0.001). Transplanted COVID-19(+) vs COVID-19(-) donors were younger, but otherwise were similar. Recipients of hearts from COVID-19+ vs COVID-19(-) donors less frequently received pre-HT inotropes (24.1% vs 31.7%, p = 0.023) and ventricular assist device therapy (29.7% vs 36.8%, p = 0.040). There were no significant differences in any post-HT outcome by donor COVID-19 status, including the primary composite outcome at 90 days (5.4% vs 5.6%, p = 0.91). Among COVID-19(+) donors, the presence of a subsequent negative test prior to transplant was not associated with posttransplant outcomes., Conclusions: Our results suggest that carefully selected COVID-19 positive donors may be used for HT with no difference in short-term post-transplant outcomes. Additional data regarding donor and recipient treatments and impact of vaccination should be collected to better inform our use of organs from COVID(+) donors., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Maternal mortality in the United States continues to increase. Cardiovascular disease, and in particular, cardiomyopathy and heart failure, serves as one of the principal causes of pregnancy-related mortality. The goal of this review is to summarize current knowledge on various cardiomyopathies in pregnancy, with an emphasis on cardiomyopathies beyond the most common in pregnancy, peripartum cardiomyopathy., Recent Findings: Although existing literature is somewhat limited, outcome studies of cardiomyopathy in pregnancy have demonstrated increased risk for adverse cardiovascular events and maternal morbidity and mortality. Herein, we review and synthesize recent studies focusing on preconception risk and counseling, pharmacologic management, and maternal outcomes in various cardiomyopathies during pregnancy including: dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, noncompaction cardiomyopathy, and chemotherapy-induced cardiomyopathy., Summary: In an effort to optimize maternal outcomes, it is critical to recognize the risk associated with various cardiomyopathies in pregnancy and understand the tools for risk stratification and antepartum management. Further research on less common cardiomyopathies in pregnancy is warranted to provide more standardized recommendations., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Leukopenia in the early period following heart transplantation (HT) is not well-studied. The aim of this study was to evaluate risk factors for the development of post-transplant leukopenia and its consequences for HT recipients., Methods: Adult patients at a large-volume transplant center who received HT between January 1, 2010 and December 31, 2020 were included. The incidence of leukopenia (WBC ≤3 × 10 3 /μL) in the first 90-days following HT, individual risk factors, and its effect on 1-year outcomes were evaluated., Results: Of 506 HT recipients, 184 (36%) developed leukopenia within 90-days. Median duration of the first leukopenia episode was 15.5 days (IQR 8-42.5 days). Individuals who developed leukopenia had lower pre-transplant WBC counts compared to those who did not (6.1 × 10 3 /μL vs. 6.9 × 10 3 /μL, p = .02). Initial immunosuppressive and infectious chemoprophylactic regimens were not significantly different between groups. Early leukopenia was associated with a higher mortality at 1-year (6.6% vs. 2.1%, p = .008; adjusted HR 3.0) and an increased risk of recurrent episodes. Rates of infection and rejection were not significantly different between the two groups., Conclusions: Leukopenia in the early period following HT is common and associated with an increased risk of mortality. Further study is needed to identify individuals at highest risk for leukopenia prior to transplant and optimize immunosuppressive and infectious chemoprophylactic regimens for this subgroup., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Heart transplantation (HT) remains the preferred therapy for patients with advanced heart failure. However, for sensitized HT candidates who have antibodies to human leukocyte antigens , finding a suitable donor can be challenging and can lead to adverse waitlist outcomes. In recent years, the number of sensitized patients awaiting HT has increased likely due to the use of durable and mechanical circulatory support as well as increasing number of candidates with underlying congenital heart disease. This State-of-the-Art review discusses the assessment of human leukocyte antigens antibodies, potential desensitization strategies including mechanisms of action and specific protocols, the approach to a potential donor including the use of complement-dependent cytotoxicity, flow cytometry, and virtual crossmatches, and peritransplant induction management., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Immunological injury to the allograft, specifically by antibodies to de novo donor specific human leukocyte antigen (dnDSA) and antibody mediated injury and rejection are the major limitations to graft survival after heart transplantation (HT). As such, our approach to allosensitization remains limited by the inability of contemporaneous immunoassays to unravel pathogenic potential of dnDSA. Additionally, the role of dnDSA is continuously evaluated with emerging methods to detect rejection. Moreover, the timing and frequency of dnDSA monitoring for early detection and risk mitigation as well as management of dnDSA remain challenging. A strategic approach to dnDSA employs diagnostic assays to determine relevant antibodies in conjunction with clinical presentation and injury/rejection of allograft to tailor therapeutics. In this review, we aim to outline contemporary knowledge involving detection, monitoring and management of dnDSA after HT. Subsequently, we propose a diagnostic and therapeutic approach that may mitigate morbidity and mortality while balancing adverse reactions from pharmacotherapy., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Noninvasive heart transplant rejection surveillance using gene expression profiling (GEP) to monitor immune activation is widely used among heart transplant programs. With the new development of donor-derived cell-free DNA (dd-cfDNA) assays, more programs are transitioning to a predominantly noninvasive rejection surveillance protocol with a reduced frequency of endomyocardial biopsies. As a result, many practical questions arise that potentially delay implementation of these valuable new tools. The purpose of this review is to provide practical guidance for clinicians transitioning toward a less invasive acute rejection monitoring protocol after heart transplantation, and to answer 10 common questions about the GEP and dd-cfDNA assays. Evidence supporting GEP and dd-cfDNA testing is reviewed, as well as guidance on test interpretation and future directions., Competing Interests: Funding Support and Author Disclosures Dr Holzhauser has been a speaker for CareDx. Dr Byku has been a consultant for Abbott. Dr De Marco has received grant support for the SHORE study from CareDx; and has been a consultant for Natera. Dr Hall has been a consultant/advisor for CareDx, Natera, Abbott, Abiomed, and Medtronic. Dr Khush has been a scientific advisor, speaker, consultant, research grant recipient for CareDx. Dr Vest has been the site principal investigator for the SHORE study for CareDx. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023. Published by Elsevier Inc.)

Pregnancy after thoracic organ transplantation is feasible for select individuals but requires multidisciplinary subspecialty care. Key components for a successful pregnancy after lung or heart transplantation include preconception and contraceptive planning, thorough risk stratification, optimization of maternal comorbidities and fetal health through careful monitoring, and open communication with shared decision-making. The goal of this consensus statement is to summarize the current evidence and provide guidance surrounding preconception counseling, patient risk assessment, medical management, maternal and fetal outcomes, obstetric management, and pharmacologic considerations., Competing Interests: Disclosure statement The authors have no conflicts of interest to disclose., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)