Comparison of waitlist and post-transplant outcomes in patients supported with total artificial heart versus continuous biventricular assist devices.

BACKGROUND: Durable biventricular support may be necessary to bridge patients with end-stage biventricular failure to heart transplantation. This study compares waitlist and post-transplant outcomes between patients supported with continuous flow, durable biventricular assist devices (BiVAD), and total artificial heart (TAH). METHODS: Using the UNOS registry, we analyzed adult (≥18 years old), first-time transplant candidates with TAH or BiVAD at the time of listing or transplantation from 10/1/2010-10/31/2020, with follow-up through 3/31/2022. Multivariable proportional subdistribution hazards models and cause-specific Cox proportional hazards models were used to compare death/deterioration or heart transplantation on the waitlist between cohorts. Kaplan-Meier and multivariable Cox proportional hazards model were used to evaluate one-year post-transplant survival and evaluate difference in outcomes based on annual transplant center volume. RESULTS: The waitlist cohort included a total of 228 patients (25% BiVAD). Waitlist outcomes between device types were similar. The transplanted cohort included a total of 352 patients (25% BiVAD). There was a trend towards worse one-year post-transplant survival in patients bridged with TAH versus BiVAD (log-rank p-value = 0.072) that persisted after adjusting for age, gender, policy, and removing dual-organ recipients (HR 1.94 (0.94, 3.98) p-value = 0.07). There was a difference in one-year post-transplant survival amongst TAH-bridged patients when stratified by annual transplant center volume (log-rank p-value = 0.013). One-year post-transplant survival between TAH-supported patients from high annual transplant volume centers and BiVAD-supported patients was similar (p-value = 0.815). CONCLUSIONS: BiVAD and TAH are reasonable support strategies with TAH implantation at high-volume transplant centers (51+ transplants/year) having similar 1-year post-transplant survival to BiVAD-supported patients.

Structural competency in global perspective.

This special issue aims to help fill two critical gaps in the growing literature as well as in practice. First, to bring together scholars and practitioners from around the world who develop, practice, review, and question structural competency with the aim of promoting a dialogue with related approaches, such as Latin American Social Medicine, Collective Health, and others, which have been key in diverse geographical and social settings. Second, to contribute to expanding structural competency beyond clinical medicine to include other health-related areas such as social work, global health, public health practice, epidemiological research, health policy, community organisation and beyond. This conceptual expansion is currently taking place in structural competency, and we hope that this volume will help to raise awareness and reinforce what is already happening. In sum, this collection of articles puts structural competency more rigorously and actively in conversation with different geographic, political, social, and professional contexts worldwide. We hope this conversation sparks further development in scholarly, political and community movements for social and health justice.

New UNOS allocation system associated with no added benefit in waitlist outcomes and worse post-transplant survival in heart-kidney patients.

BACKGROUND: The 2018 United Network for Organ Sharing (UNOS) heart transplant policy change (PC) sought to improve waitlist risk stratification to decrease waitlist mortality and promote geographically broader sharing for high-acuity patients awaiting heart transplantation. Our analysis sought to determine the effect of the UNOS PC on outcomes in patients waiting for, or who have received, a heart-kidney transplantation. METHODS: We analyzed adult (≥18 years old), first-time, heart-only and heart-kidney transplant candidates and recipients from the UNOS Registry. Patients were divided into pre-PC (PRE: October 18, 2016-May 30, 2018) and post-PC (POST: October 18, 2018-May 30, 2020) groups for comparison. Competing risks analysis (subdistribution and cause-specific hazards analyses) was performed to assess for differences in waitlist death/deterioration or heart transplantation. One-year post-transplant survival was assessed with Kaplan-Meier and Cox analyses. We included an interaction term (policy era × heart ± kidney) in our analyses to evaluate the effect of PC on outcomes in heart-kidney patients. RESULTS: One-year post-transplant survival was similar (p = 0.83) for PRE heart-kidney and heart-only recipients, but worse (p < 0.001) for POST heart-kidney vs heart-only recipients. There was a policy-era interaction between heart-kidney and heart-only recipients (HR 1.92[1.04,3.55], p = 0.038) indicating a detrimental effect of policy on 1-year survival in POST vs PRE heart-kidney recipients. No added beneficial effect of PC on waitlist outcomes in heart-kidney vs heart-only candidates was observed. CONCLUSIONS: There was no added policy-era benefit on waitlist outcomes for heart-kidney candidates when compared to heart-only candidates. POST heart-kidney recipients experienced worse 1-year survival compared to PRE heart-kidney recipients with no policy effect on heart-only recipients.

Intracellular Signaling Pathways Mediating Tyrosine Kinase Inhibitor Cardiotoxicity.

Tyrosine kinase inhibitors (TKIs) are used to treat several cancers; however, a myriad of adverse cardiotoxic effects remain a primary concern. Although hypertension (HTN) is the most common adverse effect reported with TKI therapy, incidents of arrhythmias (eg, QT prolongation, atrial fibrillation) and heart failure are also prevalent. These complications warrant further research toward understanding the mechanisms of TKI-induced cardiotoxicity. Recent literature has given some insight into the intracellular signaling pathways that may mediate TKI-induced cardiac dysfunction. In this article, we discuss the cardiotoxic effects of TKIs on cardiomyocyte function, signaling, and possible treatments.

Genetic and non-genetic risk factors associated with atrial fibrillation.

Atrial fibrillation (AF) is the most common arrhythmic disorder and its prevalence in the United States is projected to increase to more than twelve million cases in 2030. AF increases the risk of other forms of cardiovascular disease, including stroke. As the incidence of atrial fibrillation increases dramatically with age, it is paramount to elucidate risk factors underlying AF pathogenesis. Here, we review tissue and cellular pathways underlying AF, as well as critical components that impact AF susceptibility including genetic and environmental risk factors. Finally, we provide the latest information on potential links between SARS-CoV-2 and human AF. Improved understanding of mechanistic pathways holds promise in preventative care and early diagnostics, and also introduces novel targeted forms of therapy that might attenuate AF progression and maintenance.

A multi-institutional retrospective analysis on impact of RV acute mechanical support timing after LVAD implantation on 1-year mortality and predictors of RV acute mechanical support weaning.

BACKGROUND: There is little insight into which patients can be weaned off right ventricular (RV) acute mechanical circulatory support (AMCS) after left ventricular assist device (LVAD) implantation. We hypothesize that concomitant RV AMCS insertion instead of postoperative implantation will improve 1-year survival and increase the likelihood of RV AMCS weaning. METHODS: A multicenter retrospective database of 826 consecutive patients who received a HeartMate II or HVAD between January 2007 and December 2016 was analyzed. We identified 91 patients who had early RV AMCS on index admission. Cox proportional-hazards model was constructed to identify predictors of 1-year mortality post-RV AMCS implantation and competing risk modeling identified RV AMCS weaning predictors. RESULTS: There were 91 of 826 patients (11%) who required RV AMCS after CF-LVAD implantation with 51 (56%) receiving a concomitant RV AMCS and 40 (44%) implanted with a postoperative RV AMCS during their ICU stay; 48 (53%) patients were weaned from RV AMCS support. Concomitant RV AMCS with CF-LVAD insertion was associated with lower mortality (HR 0.45 [95% CI 0.26-0.80], p = 0.01) in multivariable model (which included age, BMI, angiotensin-converting enzyme inhibitor use, and heart transplantation as a time-varying covariate). In the multivariate competing risk analysis, a TPG < 12 (SHR 2.19 [95% CI 1.02-4.70], p = 0.04) and concomitant RV AMCS insertion (SHR 3.35 [95% CI 1.73-6.48], p < 0.001) were associated with a successful wean. CONCLUSIONS: In patients with RVF after LVAD implantation, concomitant RV AMCS insertion at the time of LVAD was associated with improved 1-year survival and increased chances of RV support weaning compared to postoperative insertion.

Prediction of right heart failure after left ventricular assist implantation: external validation of the EUROMACS right-sided heart failure risk score.

AIMS: Prediction of right heart failure (RHF) after left ventricular assist device (LVAD) implant remains a challenge. The EUROMACS right-sided heart failure (EUROMACS-RHF) risk score was proposed as a prediction tool for post-LVAD RHF but lacks from large external validation. The aim of our study was to externally validate the score. METHODS AND RESULTS: From January 2007 to December 2017, 878 continuous-flow LVADs were implanted at three tertiary centres. We calculated the EUROMACS-RHF score in 662 patients with complete data. We evaluated its predictive performance for early RHF defined as either (i) need for short- or long-term right-sided circulatory support, (ii) continuous inotropic support for ≥14 days, or (iii) nitric oxide for ≥48 h post-operatively. Right heart failure occurred in 211 patients (32%). When compared with non-RHF patients, pre-operatively they had higher creatinine, bilirubin, right atrial pressure, and lower INTERMACS class (P < 0.05); length of stay and in-hospital mortality were higher. Area under the ROC curve for RHF prediction of the EUROMACS-RHF score was 0.64 [95% confidence interval (CI) 0.60-0.68]. Reclassification of patients with RHF was significantly better when applying the EUROMACS-RHF risk score on top of previous published scores. Patients in the high-risk category had significantly higher in-hospital and 2-year mortality [hazard ratio: 1.64 (95% CI 1.16-2.32) P = 0.005]. CONCLUSION: In an external cohort, the EUROMACS-RHF had limited discrimination predicting RHF. The clinical utility of this score remains to be determined.

Worsening Renal Function in Cardiac Mechanical Support.

BACKGROUND: Venous congestion in heart failure (HF) may lead to worsening renal failure (WRF). We hypothesised that WRF in patients hospitalised for left ventricular assist device (LVAD) implantation is associated with increased 1-year mortality. There is limited data regarding WRF in HF patients with mechanical support. The objective of this paper is to determine whether WRF in HF patients hospitalised for LVAD implantation is associated with increased 1-year mortality and to identify risk factors for WRF. METHODS: We performed a single centre retrospective chart analysis of 162 patients who received an LVAD between August 2006 and December 2014 with pre-LVAD right heart catheterisation data. We stratified patients to those who demonstrated WRF and the use of haemodialysis (HD) or ultrafiltration (UF). RESULTS: Patients with a higher central venous pressure (CVP) >16 mmHg (17-24 mmHg range) developed WRF (29.7% vs. 14.1%, p=0.019). A CVP ≥16 and glomerular filtration rate (GFR) <30 ml/min/1.74m2 increased the odds of WRF. Worsening renal failure and HD/UF use were associated with increased 1-year mortality. Furthermore GFR <30, atherosclerosis, and right ventricular failure were independent predictors for increased 1-year mortality. A GFR <30 increased the odds of developing WRF five-fold (OR 4.14, CI [1.95-8.78], p<0.0001), and GFR <30 and central venous pressure (CVP) >16 increased the odds of requiring HD/UF. CONCLUSIONS: Worsening renal failure is associated with a higher CVP at the time of LVAD implantation and increases the risk of 1-year mortality and the odds of requiring HD/UF. Careful evaluation of renal function and comorbid conditions during LVAD implantation is critical to reduce mortality and for risk stratification.