Aims Increased shedding of extracellular vesicles (EVs)—small, lipid bilayer-delimited particles with a role in paracrine signalling—has been associated with human pathologies, e.g. atherosclerosis, but whether this is true for cardiac diseases is unknown. Methods and results Here, we used the surface antigen CD172a as a specific marker of cardiomyocyte (CM)-derived EVs; the CM origin of CD172a+ EVs was supported by their content of cardiac-specific proteins and heart-enriched microRNAs. We found that patients with aortic stenosis, ischaemic heart disease, or cardiomyopathy had higher circulating CD172a+ cardiac EV counts than did healthy subjects. Cellular stress was a major determinant of EV release from CMs, with hypoxia increasing shedding in in vitro and in vivo experiments. At the functional level, EVs isolated from the supernatant of CMs derived from human-induced pluripotent stem cells and cultured in a hypoxic atmosphere elicited a positive inotropic response in unstressed CMs, an effect we found to be dependent on an increase in the number of EVs expressing ceramide on their surface. Of potential clinical relevance, aortic stenosis patients with the highest counts of circulating cardiac CD172a+ EVs had a more favourable prognosis for transcatheter aortic valve replacement than those with lower counts. Conclusion We identified circulating CD172a+ EVs as cardiac derived, showing their release and function and providing evidence for their prognostic potential in aortic stenosis patients.
Background Malnutrition is a hallmark of frailty, is common among elderly patients, and is a predictor of poor outcomes in patients with severe symptomatic aortic stenosis (AS). The Geriatric Nutritional Risk Index (GNRI) is a simple and well‐established screening tool to predict the risk of morbidity and mortality in elderly patients. In this study, we evaluated whether GNRI may be used in the risk stratification and management of patients undergoing transcatheter aortic valve replacement (TAVR). Methods Patients with symptomatic severe AS (n = 953) who underwent transfemoral TAVR at the University Hospital Schleswig‐Holstein Kiel, Germany, between 2010 and 2019 (development cohort) were divided into two groups: normal GNRI ≥ 98 (no nutrition‐related risk; n = 618) versus low GNRI < 98 (at nutrition‐related risk; n = 335). The results were validated in an independent (validation) cohort from another high‐volume TAVR centre (n = 977). Results The low‐GNRI group had a higher proportion of female patients (59.1% vs. 52.1%), higher median age (82.9 vs. 81.8 years), prevalence of atrial fibrillation (50.4% vs. 40.0%), median logistic EuroSCORE (17.5% vs. 15.0%) and impaired left ventricular function (<35%: 10.7% vs. 6.8%), lower median estimated glomerular filtration rate (50 vs. 57 mL/min/1.73 m2) and median albumin level (3.5 vs. 4.0 g/dL) compared with the normal‐GNRI group. Among peri‐procedural complications, Acute Kidney Injury Network (AKIN) Stage 3 was more common in the low‐GNRI group (3.6% vs. 0.6%, p = 0.002). After a mean follow‐up of 21.1 months, all‐cause mortality was significantly increased in the low‐GNRI group compared with the normal‐GNRI group (p < 0.001). This was confirmed in the validation cohort (p < 0.001). Low GNRI < 98 was identified as an independent risk factor for all‐cause mortality (hazard ratio 1.44, 95% CI 1.01–2.04, p = 0.043). Other independent risk factors included albumin level < median of 4.0 g/dL, high‐sensitive troponin T in the highest quartile (> 45.0 pg/mL), N‐terminal pro‐B‐type natriuretic peptide in the highest quartile (> 3595 pg/mL), grade III–IV tricuspid regurgitation, pulmonary arterial hypertension, life‐threatening bleeding, AKIN Stage 3 and disabling stroke. Conclusions Low GNRI score was associated with an increased risk of all‐cause mortality in patients undergoing TAVR, implying that this vulnerable group may benefit from improved preventive measures.
Background Cardiovascular biomarkers constitute promising tools for improved risk stratification and prediction of outcome in patients undergoing transcatheter aortic valve implantation. We examined the association of periprocedural changes of NT‐proBNP (N‐terminal pro–B‐type natriuretic peptide) with survival after transcatheter aortic valve implantation. Methods and Results NT‐proBNP levels were measured in 704 patients before transcatheter aortic valve implantation and at discharge. Patients were grouped as responders and nonresponders depending on an NT‐proBNP–based ratio (postprocedural NT‐proBNP at discharge/preprocedural NT‐proBNP). Overall, 376 of 704 patients showed a postprocedural decrease in NT‐proBNP levels (NT‐proBNP ratio <1). Responders and nonresponders differed significantly regarding median preprocedural (2822 versus 1187 pg/mL, P <0.001) and postprocedural (1258 versus 3009 pg/mL, P <0.001) NT‐proBNP levels. Patients in the nonresponder group showed higher prevalence of atrial fibrillation (47.0% versus 39.4%, P =0.042), arterial hypertension (94.2% versus 87.5%, P =0.002), renal impairment (77.4% versus 69.1%, P =0.013), and peripheral artery disease (24.4% versus 14.6%, P =0.001). In contrast, patients in the responder group had higher prevalence of moderately reduced left ventricular ejection fraction (17.3% versus 11.0%, P =0.017), lower calculated aortic valve area (0.7 versus 0.8 cm 2 , P <0.001), and higher mean pressure gradient (41 versus 35 mm Hg, P <0.001). Median follow‐up was 22.6 months. Kaplan–Meier analysis showed a highly significant survival benefit for the responder group compared with the nonresponder group (log‐rank test, P <0.001). Conclusions A ratio based on periprocedural changes of NT‐proBNP is a simple tool for better risk stratification and is associated with survival in patients after transcatheter aortic valve implantation.
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