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Titin is a very large alternatively spliced protein that performs multiple functions in heart and skeletal muscles. A rat strain is described with an autosomal dominant mutation that alters the isoform expression of titin. While wild type animals go through a developmental program where the 3.0 MDa N2B becomes the major isoform expressed by two to three(More)
Recent studies have shown that the sequence and timing of mechanical activation of myocardium vary across the ventricular wall. However, the contributions of variable expression of myofilament protein isoforms in mediating the timing of myocardial activation in ventricular systole are not well understood. To assess the functional consequences of transmural(More)
BACKGROUND Heart failure in patients with preserved left ventricular systolic function (HFpEF) is a prevalent disease characterized by exercise intolerance with poorly understood pathophysiology. We hypothesized that recruitable contractility is impaired in HFpEF, accounting for the appearance of symptoms with exertion. METHODS AND RESULTS(More)
The rapid increase in the prevalence of chronic heart failure (CHF) worldwide underscores an urgent need to identify biomarkers for the early detection of CHF. Post-translational modifications (PTMs) are associated with many critical signaling events during disease progression and thus offer a plethora of candidate biomarkers. We have employed a top-down(More)
Myosin heavy chain (MHC) isoforms are principal determinants of work capacity in mammalian ventricular myocardium. The ventricles of large mammals including humans normally express ∼10% α-MHC on a predominantly β-MHC background, while in failing human ventricles α-MHC is virtually eliminated, suggesting that low-level α-MHC expression in normal myocardium(More)
The ventricles of small mammals express mostly alpha-myosin heavy chain (alpha-MHC), a fast isoform, whereas the ventricles of large mammals, including humans, express approximately 10% alpha-MHC on a predominately beta-MHC (slow isoform) background. In failing human ventricles, the amount of alpha-MHC is dramatically reduced, leading to the hypothesis that(More)
INTRODUCTION Reducing the form factor of an implantable cardiac monitor (ICM) may simplify device implant. This study evaluated R-wave sensing at a range of electrode distances and a preferred device implant location without mapping. METHODS Patients scheduled for a Medtronic Reveal® ICM implant (Medtronic Inc., Minneapolis, MN, USA) underwent a(More)
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