Introduction
Over the past decade, cardiac resynchronization therapy (CRT) has changed the treatment of patients with end-stage, drug-refractory heart failure. Evidence of 8 large trials (including 4,017 patients) and numerous small studies have demonstrated the benefit of CRT on heart failure symptoms, exercise capacity, and systolic left ventricular (LV) function. Various studies demonstrated reverse remodeling after CRT, with a reduction in severity of mitral regurgitation. Moreover, recent data demonstrated a reduction in heart failure hospitalization and mortality after CRT.
Various meta-analyses have subsequently been published and confirmed these beneficial effects when data from the available literature were pooled. Particularly, when the 5 available randomized, controlled trials that provided data on CRT alone were pooled (including 2,371 patients, with 1,028 control subjects and 1,343 CRT-treated patients), a 29% reduction in all-cause mortality was shown (16.9% mortality in the CRT-treated patients compared with 20.7% in control subjects). Similarly, a 38% reduction in mortality due to progressive heart failure was shown (6.7% in CRT-treated patients vs. 9.7% in control subjects). Based on the available evidence, the American Heart Association/American College of Cardiology/Heart Rhythm Society guidelines consider CRT a class I indication in patients with end-stage heart failure (New York Heart Association [NYHA] functional class III or IV) with left ventricular ejection fraction (LVEF) <35% and wide QRS complex.
A major issue confronting CRT is that, when patients are selected according to the aforementioned criteria, approximately 30% do not have a beneficial response. It should also be stressed that the patients fulfilling the selection criteria as indicated in the preceding text are certainly not equal; for example, when one looks at the plasma levels of biomarkers such as N-terminal pro-B-type natriuretic peptide, a large variance in plasma levels is noted, suggesting that some patients have worse heart failure than others, although all of them are in NYHA functional class III to IV, with LVEF <35%, and have wide QRS complex.
Cardiac dyssynchrony appears to be an important determinant for response to CRT, as demonstrated in numerous small, single-center studies, and can be derived from echocardiography. An observational study to identify echocardiographic predictors of response to CRT, known as PROSPECT (Predictors of Response to CRT), was recently published. From this study, it appeared that echocardiographic parameters had only modest accuracy to predict response to CRT, in contrast to the results from a multitude of previously published studies. In this review, we aim to explore some details of the PROSPECT study in order to gain a better understanding and to put the PROSPECT data in perspective with the remainder of existing scientific literature. In addition, we will address the contemporary and future roles of noninvasive imaging in candidates for CRT in general.