Electrophysiological remodeling in hypertrophy and heart failure

Time for primary review 28 days. Over 2 million Americans suffer from heart failure and more than 200 000 die annually. The incidence is estimated to be 400 000 per year with a prevalence of over 4.5 million, numbers that will increase with the aging of the US population 1. Despite remarkable improvements in medical therapy the prognosis of patients with myocardial failure remains poor with over 15% of patients dying within 1 year of initial diagnosis and greater than 80% 6 year mortality 2. Of the deaths in patients with heart failure, up to 50% are sudden and unexpected. The failing heart undergoes a complex series of changes in both myocyte and non-myocyte elements. In an attempt to compensate for the reduction in cardiac function the sympathetic nervous (SNS), renin–angiotensin–aldosterone (RAAS) systems and other neurohumoral mechanisms are activated. The altered signal transduction in heart failure initiates changes in gene expression that produce myocyte hypertrophy. Ultimately the changes in gene expression that initially maintain tissue perfusion prove to be maladaptive, predisposing to further myocyte loss, ventricular chamber remodeling and interstitial hyperplasia resulting in a progressive reduction in force development and impairment of ventricular relaxation. The intrinsic cardiac and peripheral responses to myocardial failure adversely alter the electrophysiology of the heart predisposing patients with heart failure to an increase in arrhythmic death. With progression of heart failure there is an increase in the frequency and complexity of ventricular ectopy 3,4. Total mortality in heart failure patients correlates with LV function and the presence of complex ventricular ectopy 5–7. However, there is no clear correlation between SCD and LV function or ventricular ectopy. In fact, data from VHeFT (Veteran’s Administration Heart Failure Trial) and other trials suggest that death is disproportionately sudden in patients with more modest myocardial dysfunction 8 … * Corresponding author. Tel.: +1-410-955-2774; fax: +1-410-955-7953