Cellular and Molecular Pathological Mechanisms in the Failing Heart Article

Cellular and Molecular Pathological Mechanisms in the Failing Heart - Article Example In many cases, however, it is not possible to arrive at a specific etiologic diagnosis, and thus it is often more desirable to classify the cardiomyopathies into one of three types dilated, restrictive, hypertrophic on the basis of differences in their pathophysiology and clinical presentation. About one in three cases of congestive heart failure (CHF) is due to dilated cardiomyopathy, with the remainder the consequence of coronary artery disease. Left and/or right ventricular systolic pump function is impaired, leading to progressive cardiac enlargement and hypertrophy, a process called remodeling. Symptoms of CHF typically appear only after remodeling has been ongoing for some time. There is, however, no close correlation between the degree of contractile dysfunction and the severity of symptoms. Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy, typically of a nondilated chamber, without obvious cause such as hypertension or aortic stenosis. Two fe atures of HCM have attracted the greatest attention: (1) asymmetric left ventricular hypertrophy, often with preferential hypertrophy of the interventricular septum; and (2) a dynamic left ventricular outflow tract pressure gradient, related to a narrowing of the subaortic area as a consequence of the midsystolic apposition of the anterior mitral valve leaflet against the hypertrophied septum. The hallmark of the restrictive cardiomyopathies is abnormal diastolic function. The ventricular walls are excessively rigid and impede ventricular filling. Myocardial fibrosis, hypertrophy, or infiltration due to a variety of causes is usually responsible. The infiltrative diseases, which represent important causes for secondary restrictive cardiomyopathy, may also show some impairment of systolic function. The inability of the ventricle to fill limits cardiac output and raises filling pressure. Therefore, exercise intolerance and dyspnea are usually the most prominent symptoms. As a result o f persistently elevated venous pressure, these patients commonly have dependent edema, ascites, and an enlarged, tender, and often pulsatile liver. The jugular venous pressure is elevated and does not fall normally, or it may rise with inspiration (Braunwald, 2005, 13-78). The current concepts in the cellular mechanism of established cardiac failure suggest that a failing heart is in an energy-depleted state. There are ongoing debate and continued research in this area, and it has been suggested that there is an imbalance between energy production and energy utilization. Human atrial myocytes have been found to be responsive to a swelling-activated outwardly rectifying chloride current. Although the exact function has still not yet been delineated, it has been suggested that these chloride currents are thought to modulate cardiac electrical activity. It has also been suggested that the hemodynamic perturbations responsible for the development of CHF and cellular hypertrophy place myocytes under mechanical stress. This, in turn would lead to complex cellular remodeling and activation of signaling systems at the intracellular levels. In a gross level, congestive heart failure is associated with cardiomyopathy, where the congestive heart failure is the resultant of cardiomyopathy. In cardiomyopathy, due to weakness of muscles of the heart, heart is not able to pump