Mechanisms Underlying Arrhythmogenesis Associated with Heart Failure

Over 5 million Americans suffer from heart failure (HF) and more than 250,000 die annually. The incidence and prevalence has continued to increase with the aging of the United States population, with approximately 600,000 new diagnoses made annually, at a cost of nearly 30 billion dollars annually. Despite remarkable improvements in medical therapy, the prognosis of patients with myocardial failure remains poor with almost 20% of patients dying within 1 year of initial diagnosis and greater than 80% 8-year mortality. Of the deaths in patients with HF, up to 50% are sudden and unexpected; indeed, patients with HF have 6 to 9 times the rate of sudden cardiac death (SCD) of the general population. Clinically, HF is a systemic syndrome resulting from impaired function of the myocardium, with symptoms arising from inadequate organ perfusion and vascular congestion. Neurohumoral activation is a prominent compensatory mechanism for inadequate myocardial performance that is ultimately maladaptive in its impact on cellular function and structure of the heart. Appropriately, research has focused on HF involving primarily the left side of the heart. Left ventricular (LV) cardiomyopathies can be generally categorized into defects of ventricular filling or a failure of