Cardiac resynchronisation therapy: when the drugs don't work.

H eart failure effects 1–2% of the population and accounts for approximately 5% of all medical admissions; despite the undoubted improvements in treatment over the past two decades, the outcome remains poor. One third of those patients admitted with decompensated heart failure die within one year of their first hospitalisation and up to 50% will be readmitted within the first six months after the initial hospitalisation. There appears little scope for further advances aimed at blocking neurohumoral maladaptive mechanisms, and other strategies, including cytokine blockade, have been disappointing. While cellular transplantation holds out considerable promise in the longer term, medically refractory heart failure remains a huge (and growing) clinical problem. Over the past decade an emerging body of evidence has suggested that biventricular and/or left ventricular pacing may provide effective palliation in some of these patients. Initial attention regarding the potential use of pacing therapy in heart failure focused on short atrioventricular (AV) delay right sided pacing to reduce pre-systolic mitral regurgitation. This phenomenon is most pronounced in patients with long AV delays, especially when left ventricular end diastolic pressure is notably raised. Despite impressive improvements in acute haemodynamic measurements in selected patients, long term results were disappointing. 9 The next target for pacing therapy was the dysynchronous contraction associated with the presence of left bundle branch block in patients with heart failure. Overall, approximately one third of patients with heart failure have a left bundle branch block pattern, although this figure rises in patients with more severe left ventricular dysfunction. By causing a dysynchronous left ventricular activation sequence, left bundle branch block impairs left ventricular contractile performance. It is not surprising, therefore, that the presence of left bundle branch block is associated with more severe symptoms and greater mortality in heart failure patients. This led to the hypothesis that simultaneously pacing the two ventricles with biventricular pacing would reduce the dysynchrony, hence the term ‘‘cardiac resynchronisation therapy’’ (CRT), and improve cardiac contractile performance and symptoms. Early acute haemodynamic studies were promising. In subsequent long term studies CRT has been shown to induce reverse remodelling and significantly reduce morbidity and re-hospitalisation in heart failure patients with prolonged QRS durations who remain severely symptomatic despite optimal medical treatment, including an angiotensin converting enzyme inhibitor/angiotensin receptor blocker, a b blocker, digoxin, and diuretics. These three large studies have shown a trend to improved survival in patients who receive CRT; however, none of these studies were appropriately powered to directly address this question. However the COMPANION study did report that combined biventricular pacing with an implantable cardioverterdefibrillator is associated with a significant reduction of total mortality. The available data from these studies has resulted in biventricular pacing being granted a class IIa indication, with a level A evidence base in the American College of Cardiology/American Heart Association/North American Society of Pacing and Electrophysiology guidelines, for heart failure patients with medically refractory, symptomatic New York Heart Association (NYHA) class III or IV limitation and prolonged QRS duration (> 130 ms), coupled with left ventricular dilatation (end diastolic diameter > 55 mm) and an ejection fraction ( 35%.