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Eligible heart failure patients with a wide QRS complex spent more time alive after use of a cardiac resynchronization therapy defibrillator (CRT-D) compared with an implantable cardioverter-defibrillator (ICD), according to long-term results of the RAFT trial.

Survivors with nearly 14 years of follow-up continued to tilt the study's all-cause mortality rates in favor of CRT-D (71.2% vs 76.4% with ICD). Time until death was significantly different between the two randomly assigned therapies (acceleration factor 0.80, 95% CI 0.69-0.92), reported a group led by John Sapp, MD, of Dalhousie University in Halifax, Nova Scotia.

A secondary outcome, the composite of death from any cause, heart transplantation, or implantation of a ventricular assist device, was also less likely with a CRT-D compared with ICD therapy (75.4% vs 77.7%, acceleration factor 0.85, 95% CI 0.74-0.98), the investigators noted in the .

"Because CRT offers remarkable improvements in functional capacity, quality of life, and survival, the principles of providing earlier treatment for heart failure might now include CRT, particularly as technology improves," wrote Lynne Warner Stevenson, MD, and Jay Montgomery, MD, both of Vanderbilt University Medical Center in Nashville, in an .

A CRT-D, also called a biventricular pacemaker, has electrodes going to both the right and left ventricles so that a pulse generator can signal them to pump with correct synchrony.

The RAFT study's showed that the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure -- albeit with more complications such as lead dislodgement, device-pocket infection, and coronary sinus dissection compared with standard ICD therapy.

Stevenson and Montgomery highlighted the benefits of CRT-D on top of heart failure medications that were standard at the time RAFT was enrolling in the 2000s. They also noted that clinical improvements could be detected "despite patient crossover from the ICD group to the CRT-D group and the inclusion of some patients who did not have a left bundle-branch block on electrocardiography and other patients who did not meet the current criteria for CRT."

Since RAFT and other trials such as and , CRT-D therapy has won some overlapping indications with ICDs.

"Enthusiasm for CRT therapy in patients with mild heart failure is likely to increase further with recent data suggesting equal or better clinical outcomes with direct left bundle-branch area pacing instead of placement of the CRT leads through the coronary sinus," Stevenson and Montgomery predicted. "Further advances in the design of pacing leads and delivery sheaths should improve the physiologic response to CRT and reduce procedural complications."

The RAFT investigators had enrolled a total of 1,798 patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more (or a paced QRS duration of 200 msec or more).

"CRT has been shown to result in significant improvement in cardiac performance and to lead to reverse remodeling, a reduction in new-onset ventricular arrhythmias, and improved clinical outcomes. It is possible that these beneficial early effects may be associated with the much longer-term improvements in overall survival shown in our trial," Sapp and colleagues surmised.

Pulling the subgroup of patients enrolled at the eight highest-enrolling sites out of 34 participating centers, the present long-term analysis included 1,050 people. The study population had a median 7.7 years of follow-up split between survivors and non-survivors. The survivors had data out to 13.9 years.

Mean age was just over 66 years, and over 80% of patients were men. Just under a quarter had NYHA class III symptoms at baseline. Additionally, 15.7% had a persistent atrial arrhythmia, 70.2% had left bundle-branch block, and 8.4% had right bundle-branch block.

Among the trial's limitations was its lack of accounting for crossovers between groups and the low representation of women and different races, Sapp and colleagues acknowledged.

"Since the initial trial was completed, pharmacologic therapy for heart failure has advanced, with the introduction of neprilysin inhibitors and [SGLT-2] inhibitors. CRT improves cardiac performance without increasing cardiac work and would be anticipated to have a complementary effect to pharmacotherapy; however, the influence of CRT on survival for patients treated with newer drugs is uncertain," they cautioned.

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