Vasohibin inhibition improves myocardial relaxation in a rat model of heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome associated with increased myocardial stiffness and cardiac filling abnormalities. Prior studies implicated increased α-tubulin detyrosination, which is catalyzed by the vasohibin enzymes, as a contributor to increased stabilization of the cardiomyocyte microtubule network (MTN) and stiffness in failing human hearts. We explored whether increased MTN detyrosination contributed to impaired diastolic function in the ZSF1 obese rat model of HFpEF and designed a small-molecule vasohibin inhibitor to ablate MTN detyrosination in vivo. Compared with ZSF1 lean and Wistar Kyoto rats, obese rats exhibited increased tubulin detyrosination concomitant with diastolic dysfunction, left atrial enlargement, and cardiac hypertrophy with a preserved left ventricle ejection fraction, consistent with an HFpEF phenotype. Ex vivo myocardial phenotyping assessed cardiomyocyte mechanics and contractility. Vasohibin inhibitor treatment of isolated cardiomyocytes from obese rats resulted in reduced stiffness and faster relaxation. Acute in vivo treatment with vasohibin inhibitor improved diastolic relaxation in ZSF1 obese rats compared with ZSF1 lean and Wistar Kyoto rats. Vasohibin inhibition also improved relaxation in isolated human cardiomyocytes from both failing and nonfailing hearts. Our data suggest the therapeutic potential for vasohibin inhibition to reduce myocardial stiffness and improve relaxation in HFpEF.

Risk of Pacemaker Implantation After Degenerative Mitral and Concomitant Tricuspid Valve Surgery.

BACKGROUND: A recent multicenter trial showed a reduction in tricuspid regurgitation (TR) progression when tricuspid annuloplasty was performed at the time of surgery for degenerative mitral regurgitation (MR), but with a 14% pacemaker (PPM) rate. We present real-world outcomes at a high-volume center for degenerative MR surgery with/without tricuspid annuloplasty. METHODS: Patients undergoing first-time degenerative mitral surgery between 2011-2021 were identified (n=1,738). After excluding patients undergoing aortic, aortic valve, or tricuspid replacement procedures, patients were stratified into mitral surgery alone (n=1,068) versus mitral surgery plus tricuspid annuloplasty (n=417). Outcomes including operative mortality, new PPM implantation, and postoperative length of stay as well as risk-adjusted overall mortality were compared. RESULTS: Among 1,485 patients in this study, 98% underwent mitral repair. Compared to concomitant tricuspid annuloplasty patients, those undergoing mitral surgery alone were 6 years younger and had lower median STS PROM. Among concomitant tricuspid repair patients, 85% (355/417) had moderate or less preoperative TR, while 15% (61/417) had severe TR. Operative mortality was 1.4%. The incidence of new PPM implantation was 0.7% (7/1,068) in the mitral only group and 5.5% (23/417) in the concomitant tricuspid group (p<0.001). Although unadjusted cumulative survival was lower in the concomitant tricuspid group, after risk adjustment, concomitant tricuspid surgery was not associated with worse overall mortality (HR 0.80 [95% CI, 0.53-1.19], p=0.27). CONCLUSIONS: Concomitant tricuspid annuloplasty is safe, with no difference in mortality and a less than 6% PPM rate at a high-volume mitral center. These data provide real-world context for concomitant tricuspid annuloplasty.

Extended criteria donor organ use for heart-lung transplantation in the modern era.

BACKGROUND: Demand for donor hearts and lungs exceeds their supply. Extended Criteria Donor (ECD) organs are used to help meet this demand, but their impact on heart-lung transplantation outcomes is poorly characterized. METHODS AND RESULTS: The United Network for Organ Sharing was queried for data on adult heart-lung transplantation recipients (n = 447) from 2005‒2021. Recipients were stratified based on whether they received ECD hearts and/or lungs. Morbidity was analyzed using Kruskal-Wallis, chi-square, and Fisher's exact tests. Mortality was analyzed using Kaplan-Meier estimation, log-rank tests and Cox regression. Sixty-five (14.5%) patients received two ECD organs, 134 (30.0%) received only an ECD lung, and 65 (14.5%) only an ECD heart. Recipients of two ECD organs were older, more likely to have diabetes, and more likely transplanted from 2015‒2021 (p < 0.05). Groups did not differ by pre-transplant diagnosis, intensive care unit disposition, life support use, or hemodynamics. Group five-year survival rates ranged from 54.5% to 63.2% (p = 0.428). Groups did not differ by 30-day mortality, strokes, graft rejection, or hospital length of stay. CONCLUSIONS: Using ECD hearts and/or lungs for heart-lung transplantation is not associated with increased mortality and is a safe strategy for increasing donor organ supply in this complex patient population.

Waitlist Trends in Heart-Liver Transplantation With Updated US Heart Allocation System.

BACKGROUND: In October 2018, the United States implemented a change in the donor heart allocation policy from a three-tiered to a six-tiered status system. The purpose of the current study was to examine changes in waitlist patterns among patients listed for concomitant heart-liver transplantation with implementation of the new allocation system. METHODS: Patients listed for heart-liver transplantation between January 1, 2012, and June 30, 2021, were identified from the United Network for Organ Sharing database. Patients were grouped by era according to initial list date before or after October 18, 2018. Competing risks regression for mortality, transplantation, removal from waitlist due to illness was performed according to the method of Fine and Gray. Waitlist data were censored at 3 years from initial listing. RESULTS: Overall, 523 patients were identified, of whom 310 were listed before (era 1, 59%) and 213 after (era 2, 41%) allocation change. Patients in era 1 were older, had more restrictive cardiomyopathy, and more preoperative inotrope use (all P < .05). However, patients in era 2 has longer ischemic times (3.5 ± 1.1 vs 3.1 ± 1.1 hours, P < .01) and more intraaortic balloon pump use (8.9% vs 3.9%, P = .016). Era 2 was associated with lower subdistribution hazard for death (hazard ratio 0.37; 95% CI, 0.13-1.02; P = .054) and increased transplantation (hazard ratio 1.35; 95% CI, 1.06-1.72; P = .015). CONCLUSIONS: The implementation of the US donor heart allocation policy was associated with more preoperative intraaortic balloon pump use for patients listed for heart-liver transplantation. Despite that, the modern era was associated with lower waitlist mortality and more frequent transplantation, without increased risk of delisting due to illness.

Extended criteria donor organ use for heart-lung transplantation in the modern era

Abstract Background: Demand for donor hearts and lungs exceeds their supply. Extended Criteria Donor (ECD) organs are used to help meet this demand, but their impact on heart-lung transplantation outcomes is poorly characterized. Methods and results: The United Network for Organ Sharing was queried for data on adult heart-lung transplantation recipients (n = 447) from 2005‒2021. Recipients were stratified based on whether they received ECD hearts and/or lungs. Morbidity was analyzed using Kruskal-Wallis, chi-square, and Fisher's exact tests. Mortality was analyzed using Kaplan-Meier estimation, log-rank tests and Cox regression. Sixty-five (14.5%) patients received two ECD organs, 134 (30.0%) received only an ECD lung, and 65 (14.5%) only an ECD heart. Recipients of two ECD organs were older, more likely to have diabetes, and more likely transplanted from 2015‒2021 (p < 0.05). Groups did not differ by pre-transplant diagnosis, intensive care unit disposition, life support use, or hemodynam-ics. Group five-year survival rates ranged from 54.5% to 63.2% (p = 0.428). Groups did not differ by 30-day mortality, strokes, graft rejection, or hospital length of stay. Conclusions: Using ECD hearts and/or lungs for heart-lung transplantation is not associated with increased mortality and is a safe strategy for increasing donor organ supply in this complex patient population.

Antithrombotic therapy for durable left ventricular assist devices - current strategies and future directions.

Left ventricular assist devices (LVADs) improve survival and quality of life for patients with advanced heart failure but are associated with high rates of thromboembolic and hemorrhagic complications. Antithrombotic therapy is required following LVAD implantation, though practices vary. Identifying a therapeutic strategy that minimizes the risks of thromboembolic and hemorrhagic complications is critical to optimizing patient outcomes and is an area of active investigation. This paper reviews strategies for initiating and maintaining antithrombotic therapy in durable LVAD recipients, focusing on those with centrifugal-flow devices.