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MyoKardia ’s Phase II trial for oHCM drug meets endpoints

MyoKardia has reported positive top-line results from the first cohort of its Phase II PIONEER-HCM clinical trial of mavacamten in patients with symptomatic, obstructive hypertrophic cardiomyopathy (oHCM).
Source: Drug Development Technology - Category: Pharmaceuticals Source Type: news

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We appreciate the interest of Menon and colleagues in the use of 3-dimensional imaging in planning surgical treatment for patients with hypertrophic cardiomyopathy.1,2 Their work is an excellent example of the application, integration, and manipulation of advanced imaging technologies into the effort to improve surgical care.
Source: The Journal of Thoracic and Cardiovascular Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: Acquired: Hypertrophic cardiomyopathy: Letters to the editor Source Type: research
We want to congratulate Hermsen and colleagues1 for their precise use of 3-dimensional (3D) printing as a guide for myectomy in hypertrophic cardiomyopathy (HCM) with left ventricular (LV) outflow tract obstruction. HCM has differing phenotypes characterized by hypertrophy of the area of the ventricle. Myectomy, although advocated as the gold standard of definitive treatment, has a very low incidence.2 This is due to a variety of factors, the chief being a steep learning curve with a paucity of experienced surgeons.
Source: The Journal of Thoracic and Cardiovascular Surgery - Category: Cardiovascular & Thoracic Surgery Authors: Tags: Acquired: Hypertrophic cardiomyopathy: Letters to the editor Source Type: research
We report the acute, short and long-term clinical and echocardiographic outcomes of our experience in a single Australian centre over 16 years.
Source: Heart, Lung and Circulation - Category: Cardiology Authors: Tags: Original Article Source Type: research
Conclusions— WGS detected nearly all variants identified on panel testing, provided 1 new diagnostic finding, and allowed interrogation of posited disease genes. Several variants of uncertain clinical use and numerous secondary genetic findings were also identified. Whereas panel testing and WGS provided similar diagnostic yield, WGS offers the advantage of reanalysis over time to incorporate advances in knowledge, but requires expertise in genomic interpretation to appropriately incorporate WGS into clinical care. Clinical Trial Registration— URL: https://clinicaltrials.gov. Unique identifier: NCT01736566.
Source: Circulation: Cardiovascular Genetics - Category: Cardiology Authors: Tags: Genetics, Functional Genomics, Cardiomyopathy Original Articles Source Type: research
Source: Circulation: Cardiovascular Genetics - Category: Cardiology Authors: Tags: Genetics, Cardiomyopathy Editorial Source Type: research
In a pathbreaking proof of concept experimental study, MYBPC3 gene mutation causing hypertrophic cardiomyopathy has been corrected in human embryos using CRISPR-Cas9 gene editing technique. Study published in Nature [1] from Oregon Health &Science University,  Portland, USA showed successful repair of the defective gene by cutting off the mutant sequence using CRISPR–Cas9. Embryos which were heterozygous for the mutation repaired the DNA break using the normal copy from the other parent. There were no off target mutations induced in the process. As always, ethical issues have to...
Source: Cardiophile MD - Category: Cardiology Authors: Tags: Cardiology cardiovascular magenetic resonance imaging CRISPR-Cas9 gene editing technique Hypertrophic cardiomyopathy MYBPC3 Source Type: blogs
The objective of this study was to evaluate the relationship between body mass index, exercise capacity, and symptoms in patients with hypertrophic cardiomyopathy (HC) and to utilize results of cardiopulmonary exercise tests (CPX) and transthoracic echocardiograms to understand the mechanism(s) of reduced exercise capacity across body mass index groups. Over a 6 year period, 510 consecutive patients with HC seen at a tertiary referral center underwent CPX and a transthoracic echocardiogram. Increasing body mass index (BMI) was associated with decreased exercise capacity as assessed by peak VO2 (mL/kg/min).
Source: The American Journal of Cardiology - Category: Cardiology Authors: Source Type: research
Conclusions— α-Galactosidase A genotype N215S does not lead to the development of a classical Fabry phenotype but induces a specific cardiac variant of Fabry disease mimicking nonobstructive hypertrophic cardiomyopathy. The lack of prominent noncardiac impairment leads to a significant delay in diagnosis and Fabry-specific therapy.
Source: Circulation: Cardiovascular Genetics - Category: Cardiology Authors: Tags: Nephrology and Kidney, Genetics, Cardiomyopathy, Hypertrophy, Cerebrovascular Disease/Stroke Original Articles Source Type: research
(Johns Hopkins Medicine) Using fruit flies, Johns Hopkins researchers have figured out why a particular inherited human heart condition that is almost always due to genetic mutations causes the heart to enlarge, thicken and fail. They found that one such mutation interferes with heart muscle's ability to relax after contracting, and prevents the heart from fully filling with blood and pumping it out.
Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
Mavacamten, formerly known as MYK-461 is a recently discovered novel small-molecule modulator of cardiac myosin that targets the underlying sarcomere hypercontractility of hypertrophic cardiomyopathy, one of the most prevalent heritable cardiovascular disorders. Studies on isolated cells and muscle fibers as well as intact animals have shown that mavacamten inhibits sarcomere force production, thereby reducing cardiac contractility. Initial mechanistic studies have suggested that mavacamten primarily reduces the steady-state ATPase activity by inhibiting the rate of phosphate release of β-cardiac myosin-S1, but the mo...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Enzymology Source Type: research
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