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.

Single lung transplantation (SLT) has been shown to be associated with worse long-term outcomes than bilateral lung transplantation (BLT), but often is performed in older adults at risk of not tolerating BLT. How do the outcomes of SLT and BLT compare among older adult recipients? The Scientific Registry of Transplant Recipients database (2005-2022) was queried for lung transplant recipients aged 65 years older. Patients were stratified by whether they underwent BLT or SLT and were propensity matched. Baseline characteristics and morbidity were compared with frequentist statistics. Survival was analyzed via Kaplan-Meier estimation. Risk factors for mortality were identified with Cox regression. Of 9,904 included patients, 4,829 patients (48.8%) underwent SLT. Patients who underwent SLT had lower lung allocation scores (39.6 vs 40.6; P < .001), more interstitial lung disease (74.4% vs 64.6%; P < .001), and lower rates of bridging (0.7% vs 2.4%; P < .001). Groups did not differ significantly by sex, BMI, or donor characteristics. Propensity matching resulted in 2,539 patients in each group. On matched analysis, patients undergoing SLT had shorter lengths of stay (14 days vs 18 day), lower reintubation rates (14.7% vs 19.8%), and less postoperative dialysis use (4.2% vs 6.4%; P < .001 for all). Patients who underwent SLT had comparable survival at 30 days (97.6% vs 97.3%; P = .414) and 1 year (85.5% vs 86.3%; P = .496), but lower survival at 5 years (45.4% vs 53.4%; P < .001) on matched analysis. SLT was a risk factor for 5-year mortality (adjusted hazard ratio, 1.19; P < .001). Our findings show that in older adults, SLT is associated with less morbidity and comparable early survival relative to BLT, but lower 5-year survival. This suggests that SLT is reasonable to perform in older adults at high risk of not tolerating BLT.

Background: Little is known regarding the impact of donor COVID‐19 status on recipient outcomes after heart transplantation. In this study, we characterize outcomes of the first 110 heart transplants from organ donors positive for COVID‐19 (COVID‐19+) in the United States. Methods and Results: Retrospective analysis of the United Network for Organ Sharing database was performed for single‐organ adult heart transplants from January 2020 to March 2022. Donor COVID‐19+ status was defined as a positive nucleic acid amplification, antigen, or other COVID‐19 test within 7 days of transplant. Nearest‐neighbor propensity score matching used to adjust for differences between recipients of COVID‐19+ and nonpositive donor hearts. Overall, 7251 heart transplants were included in analysis, with 110 using COVID‐19+ donor hearts. Recipients of COVID‐19+ allografts were younger (54 [interquartile range, 41–61]) versus 57 [46–64] years; P =0.02) but had similar rates of female sex and non‐White race compared with those receiving allografts from negative donors. Nearest‐neighbor propensity score matching resulted in 100 well‐matched pairs of recipients of COVID‐19+ versus nonpositive donor organs. The 2 matched groups had similar median lengths of stay (15 [11–23] days versus 15 [13–23] days; P =0.40), rates of graft failure (1% versus 0%; P =0.99), 30‐day death (3% versus 3%; P =0.99), and 3‐month survival (88% versus 94%; P =0.23) compared with recipients of nonpositive donors. No deaths occurred due to COVID‐19 infection among the 8 (7%) total deceased recipients of COVID‐19+ allografts to date. Conclusions: Short‐term outcomes of heart transplant recipients receiving COVID‐19+ donor organs are reassuring. However, continued monitoring for long‐term survival and potential complications are warranted.