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Background: Adverse cardiac events are common following transcatheter aortic valve replacement (TAVR). Our aim was to investigate the low left ventricular stroke volume index (LVSVI) 30 days after TAVR as an early echocardiographic marker of survival. Hypothesis: Steady‐state (30‐day) LVSVI after TAVR is associated with 1‐year mortality. Methods: A single‐center retrospective analysis of all patients undergoing TAVR from 2017 to 2019. Baseline and 30‐day post‐TAVR echocardiographic LVSVI were calculated. Patients were stratified by pre‐TAVR transaortic gradient, surgical risk, and change in transvalvular flow following TAVR. Results: This analysis focuses on 238 patients treated with TAVR. The 1‐year mortality rate was 9% and 124 (52%) patients had normal flow post‐TAVR. Of those with pre‐TAVR low flow, 67% of patients did not normalize LVSVI at 30 days. The 30‐day normal flow was associated with lower 1‐year mortality when compared to low flow (4% vs. 14%, p =.007). This association remained significant after adjusting for known predictors of risk (adjusted odds ratio [OR] of 3.45, 95% confidence interval: 1.02–11.63 [per 1 ml/m2 decrease], p =.046). Normalized transvalvular flow following TAVR was associated with reduced mortality (8%) when compared to those with persistent (15%) or new‐onset low flow (12%) (p =.01). Conclusions: LVSVI at 30 days following TAVR is an early echocardiographic predictor of 1‐year mortality and identifies patients with worse intermediate outcomes. More work is needed to understand if this short‐term imaging marker might represent a novel therapeutic target. [ABSTRACT FROM AUTHOR]

Aims: Naturally secreted nanovesicles known as exosomes are required for the regenerative effects of cardiosphere-derived cells (CDCs), and exosomes mimic the benefits of CDCs in rodents. Nevertheless, exosomes have not been studied in a translationally realistic large-animal model. We sought to optimize delivery and assess the efficacy of CDC-secreted exosomes in pig models of acute (AMI) and convalescent myocardial infarction (CMI). Methods and results: In AMI, pigs received human CDC exosomes (or vehicle) by intracoronary (IC) or open-chest intramyocardial (IM) delivery 30 min after reperfusion. No-reflowarea and infarct size (IS) were assessed histologically at 48 h. Intracoronary exosomes were ineffective, but IM exosomes decreased IS from 80±5% to 61±12% (P = 0.001) and preserved left ventricular ejection fraction (LVEF). In a randomized placebo-controlled study of CMI, pigs 4 weeks post-myocardial infarction (MI) underwent percutaneous IM delivery of vehicle (n = 6) or CDC exosomes (n = 6). Magnetic resonance imaging (MRI) performed before and 1 month after treatment revealed that exosomes (but not vehicle) preserved LV volumes and LVEF (20.1±2.2% vs. 25.4±3.6%, P = 0.01) while decreasing scar size. Histologically, exosomes decreased LV collagen content and cardiomyocyte hypertrophy while increasing vessel density. Conclusion: Cardiosphere-derived cell exosomes delivered IM decrease scarring, halt adverse remodelling and improve LVEF in porcine AMI and CMI. While conceptually attractive as cell-free therapeutic agents for myocardial infarction, exosomes have the disadvantage that IM delivery is necessary. [ABSTRACT FROM AUTHOR]