Predicting who will benefit from cardiac resynchronization therapy: results of PROSPECT
May 10, 2008 By Benjamin A. Olenchock, M.D. Ph.D. 
Cardiac resynchronization therapy (CRT) has a proven benefit in improving quality of life, functional status, and survival in select patients with NYHA class III or IV heart failure. The current indications for CRT – left ventricular ejection fraction < 35%, NYHA class III or IV, and QRS duration >130 msec – are clearly insufficient in determining exactly which patients will benefit from CRT. Given the risks and costs associated with CRT, researchers have attempted to identify various echocardiographic criteria that can predict CRT responders. The Predictors of Response to CRT (PROSPECT) trial was a multi-center, prospective trial that tested the predictive value of a myriad of echocardiography criteria. The results, published online in the journal Circulation, demonstrate that no single echocardiographic measure is useful for predicting CRT responders.
Over a 21-month period, 426 patients who met current criteria for CRT were enrolled in 53 different centers in the United States (n=227), Europe (n=194) and Hong Kong (n=5). The baseline echocardiogram was evaluated by core laboratories in Europe and the United States. Each center was trained in the acquisition of data, and poor images could be censored at the core lab’s discretion. Intra- and inter-observer variability was assessed. Echocardiographic measures included left ventricular end-systolic volume (LVESV), septal-posterior wall motion delay, the standard deviation of time to peak systolic velocity of 12 segments of the LV wass at the basal and medial levels, LV preejection interval and maximal time to peak systolic velocity difference of 6 segments at the basal level. These measures had evidence supporting their predictive value in prior single center trials.
All patients received Medtronic CRT devices. Responses to CRT were assessed by a clinical composite score (CCS) that comprised all-cause mortality, heart failure hospitalization, NYHA class and patient global assessment. The CCS score was then classified as worsened, unchanged, or improved. An additional objective measure of CRT response was defined as a reduction in LVESV of >15% at 6-months.
Of the initial 426 patients that enrolled, 286 had baseline and 6-month LVESV measurements available for analysis. The mean age was 68 years old, 71% were men, 96% were NYHA class III. By the CCS measure, 69% of patients improved, 15% had no change and 16% worsened over this time interval. For the LVESV endpoint, 56% of patients had a reduction of >15%, and 9.1% had an increase of >15% in LVESV, with a mean reduction of almost 20% at 6-months. Some of the pulsed Doppler and tissue Doppler imaging modalities achieved statistical significance in predicting CRT response by either CCS or LVESV outcome criteria. However, sensitivity and specificity analysis revealed that no single measure was very sensitive and specific.
The PROSPECT trial data suggest that there is no single echocardiographic measurement that can be used by multiple centers to select patients who will respond to CRT. We are left without data to support additional criteria to add to the current, broad selection criteria for CRT. Echocardiography has a large inter-institution variability. Results from multicenter analyses do not mean that measures that an individual center has found useful should be abandoned by that institution. Also, other imaging and electrical criteria are being studied to help tailor CRT to those that will benefit.
The PROSPECT trial was funded by Medtronic.
- Eugene S. Chung, Angel R. Leon, Luigi Tavazzi, Jing-Ping Sun, Petros Nihoyannopoulos, John Merlino, William T. Abraham, Stefano Ghio, Christophe Leclercq, Jeroen J. Bax, Cheuk-Man Yu, John Gorcsan III, Martin St. John Sutton, Johan De Sutter, and Jaime Murillo. Results of the Predictors of Response to CRT (PROSPECT) Trial. Circulation 2008: published online before print May 5, 2008.