Recent experimental results, however, call into question the necessity of normalization of wall stress that results from hypertrophic growth of the heart. Hypertrophy that occurs as a consequence of pressure overload is termed “compensatory” on the premise that it facilitates ejection performance by normalizing systolic wall stress. 12 At the molecular level, these changes in cellular phenotype are accompanied by reinduction of the so-called fetal gene program, because patterns of gene expression mimic those seen during embryonic development. Classically, 2 different hypertrophic phenotypes can be distinguished: (1) concentric hypertrophy due to pressure overload, which is characterized by parallel addition of sarcomeres and lateral growth of individual cardiomyocytes, and (2) eccentric hypertrophy due to volume overload or prior infarction, characterized by addition of sarcomeres in series and longitudinal cell growth. Even though the dichotomy between adaptive and maladaptive hypertrophy has been appreciated for more than a century, 11 mechanisms that determine how long-standing hypertrophy ultimately progresses to overt heart failure are poorly understood.Īt the cellular level, cardiomyocyte hypertrophy is characterized by an increase in cell size, enhanced protein synthesis, and heightened organization of the sarcomere. Significant morphological changes include increased rates of apoptosis, 10 fibrosis, and chamber dilation. The late-phase “remodeling” process that leads to failure is associated with functional perturbations of cellular Ca 2+ homeostasis 7 and ionic currents, 8,9 which contribute to an adverse prognosis by predisposing to ventricular dysfunction and malignant arrhythmia. In the 1960s, Meerson and colleagues 6 divided hypertrophic transformation of the heart into 3 stages: (1) developing hypertrophy, in which load exceeds output, (2) compensatory hypertrophy, in which the workload/mass ratio is normalized and resting cardiac output is maintained, and (3) overt heart failure, with ventricular dilation and progressive declines in cardiac output despite continuous activation of the hypertrophic program. 1–3 At the same time, ventricular hypertrophy is associated with significantly increased risk of heart failure and malignant arrhythmia. In these types of cardiac pathology, pressure overload-induced concentric hypertrophy is believed to have a compensatory function by diminishing wall stress and oxygen consumption. Hypertrophic growth accompanies many forms of heart disease, including ischemic disease, hypertension, heart failure, and valvular disease. Customer Service and Ordering InformationĬardiac hypertrophy is an adaptive response to pressure or volume stress, mutations of sarcomeric (or other) proteins, or loss of contractile mass from prior infarction.Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).
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