Diastolic dysfunction in coronary and hypertensive heart disease

Diastolic dysfunction is an early sign in the temporal sequence of ischemic events in coronary heart disease. The ischemic cascade, beginning with an oxygen demand supply imbalance and metabolic alterations, identifies diastolic disorders of the left ventricle (LV) as an early phenomenon, even before systolic dysfunction, ECG changes or chest pain occur. Although the physiology of diastolic function is complex, the factors contributing to diastolic disturbances can be differentiated into intrinsic and extrinsic LV abnormalities. Intrinsic mechanisms include (i) impaired L-V relaxation, (ii) increased overall chamber stiffness, (iii) increased myocardial stiffness, and (iv) increased LV asynchrony. All these factors are part of myocardial hypertrophy. The main determinant of active LV relaxation is the intracellular concentration of adenosine triphosphate (ATP). Cardiac hypertrophy, by increasing total coronary flow demand due to elevated left ventricular mass, slows the energy dependent process of relaxation resulting in a decreased concentration of calcium ATPase in the sarcoplasmic reticulum. Myocardial hypertrophy additionally leads to an increase of myocardial mass relative to the cavity volume. The degree of hypertrophy, which is the main determinant of chamber stiffness, shifts the diastolic pressure-volume relation such that the same volume is associated with a higher pressure. The main, if not unique, determinant of myocardial diastolic tissue distensibility is the structure and concentration of the collagen. Consequently tissue stiffness is augmented in coronary disease with reparative interstitial fibrosis or scar following myocardial infarction and in myocardial hypertrophy in which the LV collagen concentration is elevated due to reactive fibrosis. An increase in regional asynchrony of LV contraction and relaxation is a result of regional ischemia as well as of LV hypertrophy and tissue fibrosis. So LV asynchrony, a common sign in coronary disease, is increased by additional LV hypertrophy and fibrosis. Factors extrinsic to the LV causing diastolic disorders include (i) increased central blood volume, which will increase left ventricular pressure, without altering the LV pressure-volume relation, and (ii) ventricular interaction mediated by pericardial restraint, which may cause a parallel upward shift of the diastolic LV pressure-volume relation. Improved understanding of LV relaxation and filling helps to treat LV diastolic disturbances. Yet, treating diastolic dysfunction in coronary and/or hypertensive heart disease, both intrinsic and extrinsic abnormalities should be considered.