Frailty status measured by the Katz Index represents a powerful predictor of adverse early and late outcome after TAVI, whereas commonly used risk scores lack calibration and discrimination in a TAVI-specific patient cohort. Therefore, we propose the incorporation of this simple and reproducible measure into pre-TAVI risk assessment.

Background-The contribution of the sarcomere's thin filament to the contractile dysfunction of human cardiomyopathy is not well understood. Methods and Results-We have developed techniques to isolate and functionally characterize intact (native) thin filaments obtained from failing and nonfailing human ventricular tissue. By use of in vitro motility and force assays, native thin filaments from failing ventricular tissue exhibited a 19% increase in maximal velocity but a 27% decrease in maximal contractile force compared with nonfailing myocardium. Native thin filaments isolated from human myocardium after left ventricular assist device support demonstrated a 37% increase in contractile force. Dephosphorylation of failing native thin filaments resulted in a near-normalization of thin-filament function, implying a phosphorylation-mediated mechanism. Tissue expression of the protein kinase C isoforms ␣, ␤ 1 , and ␤ 2 was increased in failing human myocardium and reduced after left ventricular assist device support. Conclusions-These novel findings demonstrate that (1) the thin filament is a key modulator of contractile performance in the failing human heart, (2) thin-filament function is restored to near normal levels after LVAD support, and (3) the alteration of thin-filament function in failing human myocardium is mediated through phosphorylation, most likely through activation of protein kinase C.

Background-Application of pyruvate was shown to improve contractile function in isolated animal myocardium and hemodynamics in patients with congestive heart failure. We assessed the influence of pyruvate on systolic and diastolic myocardial function and its subcellular mode of action in isolated myocardium from end-stage failing human hearts. Methods and Results-In muscle strip preparations, concentration-dependent effects of pyruvate on developed and diastolic force (nϭ6), aequorin light emission reflecting intracellular Ca 2ϩ transients (nϭ6), and rapid cooling contractures reflecting sarcoplasmic reticulum (SR) Ca 2ϩ content (nϭ11) were measured. Pyruvate resulted in a concentration-dependent increase in developed force and a decrease in diastolic force, with a maximum effect of 155% and 21%, respectively, at 20 mmol/L pyruvate (PϽ0.05). This was associated with a dose-dependent prolongation of time to peak tension and relaxation time.