Cardiac resynchronization therapy in patients with chronic heart failure: pathophysiology and current experience

Congestive heart failure afflicts 2 to 4 million people in the US and nearly 15 million people worldwide. Accepted goals of heart failure treatment include: improvement of symptoms;prevention of disease progression; and reduction in morbidity and mortality. Complex pharmacological therapies achieve these goals, but not in all patients with heart failure. Cardiac resynchronization therapy (CRT) represents a new therapeutic approach in patients with chronic heart failure. CRT is only applicable to a subgroup of patients with ventricular conduction system delay, characterized by prolonged QRS duration. Bundle branch block impacts 20 to 30% of patients with New York Heart Association (NYHA) functional class III-IV heart failure and consists predominantly of left bundle branch block. When left ventricular (LV) conduction delay is superimposed upon ventricular dysfunction, it appears to be a marker of disease severity. These conduction abnormalities have deleterious effects both on systolic function and LV filling, and they can induce or enhance mitral functional regurgitation. CRT attempts to correct the deleterious effect of dysynchrony by increasing LV filling time, decreasing septal dyskinesis and reducing mitral regurgitation. Several observational studies and randomized, controlled trials have shown the benefit of CRT in a subgroup of patients with heart failure, with conduction delays. Improvements were found in the mean distance walked in 6 minutes, quality of life (QOL), NYHA functional class, in peak oxygen uptake (V-dot(2)), total exercise time, reduction of hospitalization, LV function and reduction of the LV end-diastolic diameter. These studies support the therapeutic value of ventricular resynchronization in patients with severe heart failure, who have intraventricular conduction delay but who do not have a standard indication for the implantation of a pacemaker. In respect to these study results, possible indications for a biventricular pacing device at this time are as follows: NYHA functional class III, LV ejection fraction <35%, sinus rhythm, QRS duration >150 msec and drug refractory despite individual optimal heart failure therapy. CRT significantly improved symptoms, exercise tolerance and QOL in most patients. However, further studies are needed to assess long-term clinical effects and prognosis, as well as economic benefit of this therapeutic approach.