Myocardial Ischemia: Morbid Demand
Erling Falk, Prediman Shah, Pim de Feyter in Ischemic Heart Disease, 2007
DEFINITION Myocardial hypertrophy is defined as excessive cardiomyocyte growth with protein synthesis and organization of sarcomeres, accompanied by interstitial collagen deposition and growth of the vascular compartment1. This is a self-limited response triggered by elevated extrinsic or intrinsic biomechanical stress within the myocardium. In the human ventricle, parallel and reproducible increases in cell diameter, volume, and nuclear area characterize ‘hypertrophic’ growth but are accompanied by extracellular matrix (ECM) and interstitial changes that ultimately ‘stiffen’ the hypertrophied myocardium, which affects diastole, resulting in clinical symptoms. Macroscopically, hypertrophy is characterized by wall thickening and near obliteration of the ventricular cavity (91). Classification of cardiac hypertrophy is divided into physiologic and pathologic conditions (Table 10).
Cardiac hypertrophy, heart failure and cardiomyopathy
Mary Sheppard in Practical Cardiovascular Pathology, 2nd edition, 2011
Cardiac Hypertrophy In order to maintain sufficient cardiac output over an expected lifespan of 70-plus years, the heart must respond to myriad physiologic and pathophysiologic stimuli. To meet these physiological demands on a day-to-day basis, the heart relies on a phenomenon known as myocardial reserve, whereby it can reversibly alter cardiac output in response to a sudden increase in demand via a broad range of myocellular signalling pathways anchored, in part, by the β-adrenergic system. However, sustained or progressive demands on the heart can result in cardiac hypertrophy. Many common disease states including hypertension, valvular disease and post-myocardial infarction lead to increase in haemodynamic demand (either pressure-or volume-based) that causes the characteristic pathogenic myocellular hypertrophy. If the inciting pathogenic stimulus is not relieved, the ‘adaptive’ increase in myocellular mass leads to impaired ventricular relaxation, filling and eventual cardiac failure. Given the continuing high incidence of these diseases and the resultant morbidity and mortality, understanding the pathogenesis of hypertrophic heart disease remains a central focus of cardiovascular research today.
Cardiac Hypertrophy, Heart Failure and Cardiomyopathy
Mary N. Sheppard in Practical Cardiovascular Pathology, 2022
Cardiomyocytes exit the cell cycle and become terminally differentiated soon after birth. Both physiological and pathological hypertrophy involve enlargement of individual cardiomyocytes, but the characteristics of each type of hypertrophy are distinct. In general, myocardial hypertrophy is observed to accompany a diminished left ventricular function, cardiac arrhythmias and heart failure in patients with these conditions. The selection of drugs varies depending on the aetiology of the cardiac hypertrophy. The surface area of the myocardium staining as collagen may reach 25% in severe hypertrophy, and is distributed both as coarse strands and a more diffuse fine interstitial fibrosis. Cardiomyopathies are diseases of heart muscle. The term cardiomyopathy implies that the functional abnormality lies within the myocardium itself. In 1968, the World Health Organization defined cardiomyopathies as ‘diseases of different and often unknown aetiology in which the dominant feature is cardiomegaly and heart failure’.
Echocardiographic Left Ventricular Hypertrophy: Clinical Characteristics. The Framingham Heart Study
Published in Clinical and Experimental Hypertension. Part A: Theory and Practice, 1992
Daniel Levy, Joanne M. Murabito, Keaven M. Anderson, Jane C. Christiansen, William P. Castelli
Recent data suggest that echocardiographic left ventricular (LV) hypertrophy is associated with increased cardiovascular morbidity and mortality. Based upon application of sex-specific echocardiographic criteria for LV hypertrophy, the clinical characteristics of 863 subjects with and 4097 subjects without LV hypertrophy are examined. Subjects with LV hypertrophy are older, more obese, have higher blood pressure, and are more likely to have pre-existing coronary artery disease. In addition subjects with LV hypertrophy have a higher prevalence of reduced echocardiographic fractional shortening. We conclude that subjects with echocardiographic LV hypertrophy are at high risk for cardiovascular disease complications by virtue of their clinical profile. Additional investigation of the benefits of therapeutic interventions directed toward the prevention or regression of LV hypertrophy is warranted.
Risk Reduction Following Regression of Cardiac Hypertrophy
Published in Clinical and Experimental Hypertension. Part A: Theory and Practice, 1990
Cardiac hypertrophy in essential hypertension is documented to be an independent risk factor for congestive heart failure, coronary heart disease and cardiac sudden death. Reduction of left ventricular hypertrophy therefore emerged as a new challenge of antihypertensive treatment. Sympatholytic agents, calcium entry blockers, and angiotensin converting enzyme inhibitors have been found to reduce left ventricular hypertrophy, whereas vasodilators (and most likely also diuretics) are unable to reduce left ventricular mass despite good control of arterial hypertension. Several studies indicated that reduction of left ventricular hypertrophy is not detrimental to cardiac pump function: systolic and diastolic function were found to be maintained at rest and during exposure to increased pressure load. In hypertensive patients with left ventricular hypertrophy ventricular arrythmias have been reported to be increased and to be the pathophysiological link for the increased risk of cardiac sudden death. Reduction of cardiac hypertrophy was found to be accompanied by a reduction of prevalence and severity of ventricular arrhythmias if treated with betablockers, calcium entry blockers or converting enzyme inhibitors. Whether reduction of cardiac hypertrophy indeed decreases the cardiovascular risk attributed to left ventricular hypertrophy is unknown at present, although clinical studies support such a viewpoint.
Targeting calcineurin and associated pathways in cardiac hypertrophy and failure
Published in Expert Opinion on Therapeutic Targets, 2005
Cardiac hypertrophy occurs in response to long-term increases in haemodynamic load related to a variety of physiological and pathological conditions. Cardiac hypertrophy developing in pathological conditions with increased load often progresses to a decompensated stage with cardiac contractile dysfunction, clinical signs of heart failure and premature death. Cardiac hypertrophy associated with adverse outcomes is said to be maladaptive. Conversely, there are settings where cardiac hypertrophy appears to be purely adaptive (e.g., hypertrophy in response to regular physical exercise). In these circumstances, hypertrophy is associated with preserved contractile performance and a favourable prognosis. Cardiac myocyte hypertrophy is controlled by growth factor receptors and mechanical stress sensors which activate a complex network of signalling pathways. These pathways promote a multitude of qualitative and quantitative changes in gene expression levels in cardiomyocytes. Reprogramming of gene expression, much more than cardiac (myocyte) hypertrophy per se, ultimately determines if cardiac hypertrophy will be adaptive or maladaptive. Pharmacological modification of gene expression in the hypertrophied heart may, therefore, be an attractive approach to prevent or even treat maladaptive hypertrophy and heart failure. Calcineurin is a serine-threonine phosphatase that is activated by sustained increases in [Ca2+]i in cardiomyocytes. Although it has been firmly established that calcineurin plays a critical role in the development of cardiac hypertrophy, the question of whether calcineurin activation serves an adaptive or maladaptive role is still unresolved. An answer to this question is crucial if calcineurin is to be developed as a drug target. The authors propose that calcineurin acts as a double-edged sword; excessive activation of calcineurin is maladaptive, its activation at endogenous levels and at specific subcellular microdomains, however, promotes adaptation. Calcineurin itself may, therefore, not be a convenient target for drug development. However, because maladaptive hypertrophy is ultimately a transcriptional disorder, definition of the transcriptional programme activated by distinct calcineurin activation levels may permit identification of novel, attractive drug targets.
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