Late Sodium Current Inhibition Reverses Electro-Mechanical Dysfunction in Human Hypertrophic Cardiomyopathy Running title: Coppini et al.; Ranolazine on myocytes from HCM patients
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Response to letter regarding article, "Late sodium current inhibition reverses electromechanical dysfunction in human hypertrophic cardiomyopathy".
BACKGROUND Hypertrophic cardiomyopathy (HCM), the most common mendelian heart disorder, remains an orphan of disease-specific pharmacological treatment because of the limited understanding of cellular mechanisms underlying arrhythmogenicity and diastolic dysfunction. METHODS AND RESULTS We assessed the electromechanical profile of cardiomyocytes from 26 HCM patients undergoing myectomy compar...
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BACKGROUND Current therapies are ineffective in preventing the development of cardiac phenotype in young carriers of mutations associated with hypertrophic cardiomyopathy (HCM). Ranolazine, a late Na+ current blocker, reduced the electromechanical dysfunction of human HCM myocardium in vitro. METHODS AND RESULTS To test whether long-term treatment prevents cardiomyopathy in vivo, transgenic m...
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Transmembrane sodium (Na(+)) fluxes and intracellular sodium homeostasis are central players in the physiology of the cardiac myocyte, since they are crucial for both cell excitability and for the regulation of the intracellular calcium concentration. Furthermore, Na(+) fluxes across the membrane of mitochondria affect the concentration of protons and calcium in the matrix, regulating mitochond...
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The D-loop region is a hot spot for mitochondrial DNA (mtDNA) alterations, containing two hypervariable segments, HVS-I and HVS-II. In order to identify polymorphic sites and potential genetic background accounting for Hypertrophic CardioMyopathy (HCM) disease, the complete non-coding region of mtDNA from 31 unrelated HCM patients and 45 normal controls were sequenced. The sequences were aligne...
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Introduction: Accurate delineation of myocardial fibrosis in Late Gadolinium Enhancement on Cardiac Magnetic Resonance (LGE-CMR) has a crucial role in the assessment and risk stratification of HCM patients. As this is time-consuming and requires expertise, automation can be essential in accelerating this process. This study aims to use Unet-based deep learning methods to automate the mentioned ...
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