Background Cardiac muscle hypercontractility is a key pathophysiological abnormality in hypertrophic cardiomyopathy, and a major determinant of dynamic left ventricular outflow tract (LVOT) obstruction. Available pharmacological options for hypertrophic cardiomyopathy are inadequate or poorly tolerated and are not disease-specific. We aimed to assess the efficacy and safety of mavacamten, a first-in-class cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy. Methods In this phase 3, randomised, double-blind, placebo-controlled trial (EXPLORER-HCM) in 68 clinical cardiovascular centres in 13 countries, patients with hypertrophic cardiomyopathy with an LVOT gradient of 50 mm Hg or greater and New York Heart Association (NYHA) class II-III symptoms were assigned (1:1) to receive mavacamten (starting at 5 mg) or placebo for 30 weeks. Visits for assessment of patient status occurred every 2-4 weeks. Serial evaluations included echocardiogram, electrocardiogram, and blood collection for laboratory tests and mavacamten plasma concentration. The primary endpoint was a 1•5 mL/kg per min or greater increase in peak oxygen consumption (pVO 2) and at least one NYHA class reduction or a 3•0 mL/kg per min or greater pVO 2 increase without NYHA class worsening. Secondary endpoints assessed changes in post-exercise LVOT gradient, pVO 2 , NYHA class, Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS), and Hypertrophic Cardiomyopathy Symptom Questionnaire Shortness-of-Breath subscore (HCMSQ-SoB). This study is registered with ClinicalTrials.gov, NCT03470545.

Doppler echocardiography may provide a reliable, noninvasive method to determine PVR.

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Tissue Doppler imaging (TDI) and TDI-derived strain imaging are robust physiologic tools used for the noninvasive assessment of regional myocardial function. Due to high temporal and spatial resolution, regional function can be assessed for each phase of the cardiac cycle and within the transmural layers of the myocardial wall. Newer techniques that measure myocardial motion by speckle tracking in grayscale images have overcome the angle dependence of TDI strain, allowing for measurement of 2-dimensional strain and cardiac rotation. TDI, TDI strain, and speckle tracking may provide unique information that deciphers the deformation sequence of complexly oriented myofibers in the left ventricular wall. The data are, however, limited. This review examines the structure and function of the left ventricle relative to the potential clinical application of TDI and speckle tracking in assessing the global mechanical sequence of the left ventricle in vivo.The spiral arrangement of muscle fibers in the heart is reminiscent of spiral and vortex patterns in nature, ranging from small organelles and whirlpools to hurricanes and rotational patterns of the galaxies (1-5). Vortex patterns link two fundamental forms of motion that work in close balance: an inner, rapidly descending swirl and an outer, less rapid, ascending rotation (4) ( Fig. 1 A-C). These counterdirectional movements of a vortex produce suction and expulsion forces that have been exploited for designing energy efficient propellers and turbines (6). Likewise, experimental and mathematical modeling of the clockwise and counterclockwise spiral loops of myofibers in the left ventricle (LV) has shown that counterdirectional geometry provides an efficient distribution of regional stresses and strains (7). Conversely, altered ventricular geometry resulting from cardiac remodeling, regional myocardial dysfunction, or asynchronous conduction distort the efficiency of the loading and expulsion dynamics (8,9). In this review, we associate the LV myofiber architecture to the spatiotemporal sequence of regional deformations occurring during normal cardiac contraction and relaxation. We further elucidate experimental observations, which explore the application of tissue Doppler imaging (TDI) and 2-dimensional ultrasound speckle tracking for delineation of the synchronous mechanical shortening and lengthening sequences of the human LV.Address reprint requests to Marek Belohlavek, Division of Cardiovascular Diseases, Mayo Clinic, 13400 East Shea Boulevard Scottsdale, AZ 85259, E-mail address for author named in reprint line: Belohlavek.marek@mayo.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect th...