JACC: Reverse remodeling can predict HF, VTA after CRT-D
Reverse remodeling can significantly reduce the risk of subsequent life-threatening ventricular tachyarrhythmias (VTA) in patients with left ventricular dysfunction, researchers found during a substudy of the MADIT-CRT trial. These data add to the ample evidence released at this year’s Heart Rhythm Society in San Francisco showing that certain risk factors can increase the risk of VTA post-cardiac synchronization therapy with defibrillator (CRT-D).

In the current study published June 14 in the Journal of the American College of Cardiology, Alon Barsheshet, MD, of the University of Rochester Medical Center in Rochester, N.Y., and colleagues evaluated the association between echocardiographic response to CRT and subsequent  VTA in 1,372 patients. Of the 1,372 patients, 623 were implanted with an implantable cardioverter-defibrillator (ICD) and 749 patients had CRT-D.

Within the CRT arm, 529 patients were considered high responders (having a 25 percent or greater reduction in left ventricular end-systolic volume [LVESV]) and 220 patients were low responders (<25 percent reduction in LVESV).

The researchers reported that high responders had greater reductions in left ventricular end-diastolic volume (LVEDV) and left ventricular mass compared with low responders. However, low responders saw greater reductions in left ventricular volumes and left ventricular mass compared with patients within the ICD arm. Only 4.8 percent of patients in the ICD arm had >25 percent reduction in LVESV.

Within the study population, 55 patients died during follow-up and 184 patients experienced appropriate ICD therapy for an arrythmia.

CRT-D low responders saw the greatest echocardiographic response compared with ICD-only patients and high responders to CRT-D. These rates were 28 percent, 21 percent and 12 percent, respectively. At two years, the endpoints of VTA or death were highest among low responders, intermediate among ICD-only patients and lowest in high responders to CRT-D.

During a multivariate analysis, the researchers found that high responders had a 55 percent lower risk of VTA compared with ICD-only patients. Additionally, they found that the risk of VTA among low responders did not statistically differ from ICD-only patients. Patients who received CRT-D and who were high responders had a 64 percent lower risk of VTA compared with low responders.

“We showed that patients with a high echocardiographic response to CRT-D exhibit a significant reduction in the risk of life-threatening VTA events, whereas VTA risk among patients with a low echocardiographic response to CRT-D was not significantly different from that of ICD-only patients,” Barsheshet et al wrote.

This suggested that reverse remodeling that is induced by CRT in mechanical and electrical stability of the left ventricle can decrease the risk of heart failure and arrhythmic events in patients who have a good response to echocardiography post-device implantation.

While previous studies have shown that left ventricular size and adverse remodeling can predict ventricular arrhythmias, the current study showed that reverse ventricular remodeling is related to the risk of future VTA events. “Every 10 percent reduction in LVESV was associated with a significant reduction in all the following endpoints: VTA, VTA/death, and VT [ventricular tachycardia], whereas the most striking reduction was in VF [ventricular fibrillation] events,” the authors wrote.

However, study authors said that a limitation of the study is the lacking echocardiographic data. In an accompanying editorial, Anne B. Curtis, MD, of the University at Buffalo in Buffalo, N.Y., said these lack of data are due to the fact that the FDA requested that CRT be turned off during one-year echocardiograms. But despite these limitations, Curtis offered that the substudy results are valuable because it confirms previous study results in mild HF patient populations.

In a similar substudy of MADIT-CRT presented at HRS.11, also by University of Rochester Medical Center researchers, the authors found that CRT-D can reduce heart failure or death and improve left ventricular size in patients with a LVEF <30 percent, a wide QRS and mild heart failure. The current study results were comparable.

“Our findings extend this observation and show that responders to CRT-D therapy derive a significant reduction in the risk of life-threatening VTA, suggesting that reverse remodeling had a dual effect of both HF and VTA risk reduction in the MADIT-CRT study population,” Barsheshet and colleagues concluded.

They stressed that reverse remodeling should be used as a marker for HF and VTA risk post-CRT-D implantation.

Curtis surmised that "CRT in mild heart failure, when it is successful in promoting reverse ventricular remodeling, reduces the risk of ventricular tachyarrhythmias compared with ICD therapy alone." However,  "on the other hand," she said that "biventricular pacing with epicardial left ventricular pacing without improvement in ventricular size and function appears to be proarrhythmic."

CRT patients must be selected carefully, said Curtis, and response to CRT is "the best insurance that patients will have optimal outcomes in follow-up."