Left ventricular dysfunction: causes, natural history, and hopes for reversal

Left ventricular dysfunction (LVD) with subsequent congestive heart failure (CHF) constitutes the final common pathway for a host of cardiac disorders. Coronary artery narrowing or ischaemic heart disease is the dominant cause of heart failure and is often associated with acute or prior myocardial infarction. The remaining aetiologies include cardiomyopathy, hypertension, and a variety of other factors such as valve disease or myocarditis. Heart failure is an enormous problem. Data from the Framingham heart study shows that it develops in approximately 16% of men and 18% of women who have diabetes; 12% of men and 8% of women who have hypertension; and 30% of both sexes who have myocardial infarction.1 Interestingly, over the second half of the 20th century there has been a striking increase in the frequency of coronary artery disease and diabetes as aetiological factors for CHF, whereas the impact of hypertension and rheumatic valve disease has declined. LVD produces many changes in the structure and function of the heart through a variety of mechanisms. The muscle of the heart is encased in a collagen weave. There are interstitial spaces that are associated with a variety of elements, a number of which can contribute to the development of CHF. The extracellular matrix has a scaffolding function, which supports myocytes and blood vessels. It also provides lateral connections between the cells and muscular bundles that govern not only the architecture of the heart, but also its ability to contract. Moreover, the extracellular matrix contributes to the heart's tensile strength and resilience, which helps resist deformation, maintaining the elliptical shape of the heart and its thickness. Once left ventricular dysfunction occurs a series of compensatory mechanisms are triggered which lead to a host of …