Francis J. Podbielski, MD, FCCP, comments on CRT-D
Patients with mild heart failure who received a cardiac resynchronization device had significantly reduced rates of hospitalizations for heart failure during follow-up of 1,820 patients for an average of 5.6 years, identifying in this post hoc analysis another benefit from this device that patients potentially receive in addition to an established survival advantage.
Extended follow-up of patients enrolled in the MADIT-CRT trial showed that patients with either New York Heart Association (NYHA) class I or II cardiomyopathy who received a cardiac resynchronization device with a defibrillator (CRT-D) had a significant reduction in all-cause hospitalization during follow-up, compared with control patients randomized to receive an implantable cardioverter defibrillator (ICD) device. This reduction in all hospitalizations was specifically driven by a significant reduction in cardiovascular hospitalizations, and the drop in cardiovascular hospitalizations was specifically driven by a cut in hospitalizations for heart failure (HHF), Sabu Thomas, MD, said at the annual scientific meeting of the Heart Failure Society of America.
The data showed that during follow-up all-cause hospitalizations occurred in 73% of the CRT-D patients and 83% of those who received an ICD; cardiovascular hospitalizations happened in 29% of the CRT-D patients and in 43% of those with an ICD; and HHF occurred in 12% of the CRT-D patients and in 22% of those with an ICD, reported Dr. Thomas, a heart failure cardiologist at the University of Rochester (N.Y.) Medical Center. All three between-group differences were statistically significant for these post hoc endpoints.
These reduced hospitalizations also linked with better survival. Patients in the trial database with cardiovascular hospitalizations had a nearly fourfold higher rate of death, compared with nonhospitalized patients, Dr. Thomas said.
The findings “suggest that this device [CRT-D] has sustained benefit in these patients for up to 7 years,” said Dr. Thomas and his collaborator, Valentina Kutyifa, MD, in an interview. “However, this was only seen in patients with left bundle branch block [LBBB].” In patients with non-LBBB, CRT-D was not associated with a reduction in [cardiovascular] hospitalizations.
The LBBB connection
In a multivariate analysis, the 1,281 patients with LBBB (70% of the study cohort) who were more than 6 months out from device placement had a significant 43% relative cut in their incidence of cardiovascular hospitalizations, compared with that of control patients who received an ICD, while the 537 patients with non-LBBB showed no benefit from CRT-D treatment, compared with those who received an ICD, for reducing cardiovascular hospitalizations. (Data from two enrolled patients weren’t available for the analyses.) This finding that the HHF benefit focused in patients with LBBB was consistent with many prior observations that CRT-D was most effective in this patient subgroup.
The researchers also highlighted that their findings apply only to patients with NYHA functional class I or II heart failure with reduced ejection fraction (HFrEF), the only types of patients enrolled in the MADIT-CRT trial (15% had class I disease).
The results also showed that, during the first 6 months on CRT-D treatment, patients with a LBBB showed a significant 43% increase in their cardiovascular hospitalizations, compared with control patients, which may have been driven by device-related events. “We did not investigate this in detail, and it needs more study,” said Dr. Thomas and Dr. Kutyifa, a cardiac electrophysiologist at the University of Rochester.Their new findings extend the initial, prespecified results of the MADIT-CRT (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy) trial, which was designed to examine a primary endpoint of death from any cause or a nonfatal heart failure event. During the initial average follow-up of 2.4 years, patients who received a CRT-D device had a significant relative reduction in this endpoint of 34%, compared with patients on ICD treatment, exclusively in patients with LBBB. Extended follow-up for as long as 7 years of the same cohort showed a continued significant reduction of all-cause death compared with controls, a 41% relative risk reduction, that again was only apparent in patients with LBBB.
The MADIT-CRT findings are generally consistent with prevailing CRT-D recommendations from the American College of Cardiology and American Heart Association from 2013 that give a class I indication (“is indicated”) for using the device in heart failure patients with LBBB, a QRS interval of at least 150 msec, NYHA class II-IV function, and a left ventricular ejection fraction no greater than 35%. A lesser, class IIa recommendation (“can be useful”) exists for patients with a narrower QRS of 120-149 msec with the other class I criteria, and for patients with non-LBBB the recommendation drops to class IIb (“may be considered”).