New insights into cardiac resynchronization therapy

Ventricular dyssynchrony plays a central role in the expression and progression of heart failure (HF). An independent risk factor for cardiac mortality, ventricular dyssynchrony is characterized by delay in left ventricular (LV) lateral wall contraction. This leads to decreased pumping efficiency, with resulting fluid retention and impaired exercise tolerance. Cardiac resynchronization therapy (CRT) attempts to improve cardiac efficiency by restoring the normal mechanical relationship between right and left ventricular contraction. Cardiac output increases with resynchronization, while ventricular filling pressure decreases without increasing cardiac oxygen consumption. Cardiac resynchronization therapy can also reverse LV dysfunction and reduce mitral regurgitation in patients with HF. Since 1999, the efficacy of implantable CRT devices has been evaluated in clinical trials enrolling more than 4,000 patients with heart disease. In the CARE-HF trial, CRT reduced the risk of death by 36% relative to standard pharmacologic therapy. Combining CRT with a defibrillator might produce an added benefit. In the COMPANION trial, all-cause mortality in patients randomized to a CRT-defibrillator combination was less than in patients receiving CRT therapy alone. Cardiac resynchronization therapy has also been found to decrease morbidity and improve functional status and quality of life. At the present time, the indications for CRT are limited and include symptomatic HF despite optimal medical therapy, prolonged QRS interval, and LVEF ≤ 35%. However, indications for CRT are still evolving and may be expanded as further studies identify those most likely to benefit.