Device Therapy in Heart Failure Management: A Comparison of Right Ventricular, Left Ventricular, and Biventricular Pacing Strategies

a. Background Heart failure is a disease of immense burden and cost to individuals and society. It is estimated that over 4.5 million people in the United States currently suffer from heart failure and over 400,000 cases are newly diagnosed each year (1). The prevalence of the disease increases with age such that nearly 10% of the population will be affected in the ninth decade of life (2). Further, heart failure is the leading cause of hospitalizations of individuals over 65 years of age and it is estimated that there will be over one million hospitalizations for heart failure this year with an economic cost of over $40 billion (3). Given the tremendous scope of heart failure, a great deal of research has gone into finding therapies that can reduce its morbidity and mortality. Numerous trials have resulted in guidelines which currently recommend the use of beta-blockers, angiotensin converting enzyme (ACE) inhibitors, diuretics, aldosterone antagonists, and digoxin for the treatment of heart failure patients at various stages of the disease (4). Despite these advances in the pharmacological management of heart failure patients, it is clear that there still remain a significant number of patients with persistent symptoms while on maximal medical therapy. More importantly, heart failure continues to be one of the most progressive and lethal diseases and still directly and indirectly contributes to 250,000 deaths annually (4). Given the likelihood that the personal, societal, and economic burden of heart failure will only grow as the number of individuals over the age of 65 increases in the next few decades, it is imperative that all varieties of therapies that can potentially reduce morbidity and mortality be fully explored and utilized. An important characteristic of heart failure is the presence of dysrhythmias and conduction system abnormalities. Some have estimated that up to 53% of heart failure patients have intraventricular conduction delays that can lead to abnormal electrical depolarization and subsequent dyssynchrony between the right ventricle (RV) and left ventricle (LV) (5). While many efforts have focused on other aspects of heart failure such as optimization of preload, afterload, and contractility, recent technological breakthroughs have now made addressing the correction of ventricular dyssynchrony a possibility. This is of significance since the consequences of ventricular dyssynchrony, including abnormal interventricular septal wall motion, reduction in stroke volume, reduction in the rate of rise of left ventricular pressure, diminished diastolic filling times, and prolongation of mitral regurgitation, all contribute, worsening heart failure and can cause symptomatic deterioration (6-8). To identify patients in whom ventricular dyssyncbrony may be a problem, the presence of a bundle branch block or interventricular conduction delay on a standard electrocardiogram has been used since these findings are the manifestation of ventricular dyssynchrony. In fact, the presence of a wide QRS complex has been shown to be an independent or contributing risk factor in patients with heart failure, presumably because of the dyssynchrony it represents (5, 9-12). While pacemakers were primarily designed to treat atrioventricular (AV) and sinus node conduction defects, numerous pacing strategies were attempted to resynchronize electrical depolarization prior to the development of current biventricular (BV) systems. Attempts to manipulate parameters, such as the AV delay, of traditional pacemakers which have right atrial (RA) and RV leads have yielded inconsistent results and in certain cases have worsened ventricular dyssynchrony (6-8, 13-20).