Medical Device Daily Washington Editor

DENVER — Data from the Block HF trial, sponsored by Medtronic (Minneapolis) were recently published in the New England Journal of Medicine, and the results seem to nudge the biventricular pacing argument a bit further for some heart failure patients. Anne Curtis, MD, formerly the president of the Heart Rhythm Society (Washington), told Medical Device Daily the data "tell us the patients will do better" on cardiac resychronization therapy compared to pacing of only the right ventricle. Medtronic is said to have an FDA application in the works for an expanded indication for its pacemakers, which if successful could help the firm cement its place in this sector of the electrophysiology business.

Medtronic reported May 11 that the data from Block HF "showed a marked reduction in heart failure-related symptoms for patients with atrioventricular (AV) block and left ventricular (LV) systolic dysfunction at six, 12, 18 and 24 months." The company stated also that the data suggest that pacing for both ventricles as opposed to right ventricle-only pacing only offers "a considerable improvement in quality of life,"

The abstract in NEJM says that the study evaluated whether biventricular pacing could reduce mortality, morbidity, and adverse remodeling in the left ventricle, with outcomes including time to all-cause death, urgent care visit for heart failure requiring intravenous therapy, and a 15% or more increase in the left ventricular end-systolic volume index.

Enrollees were those with atrioventricular block and heart failure rated class I, II or III under the New York Heart Association (NYHA) scheme, and inclusion criteria included left ventricular ejection fractions of 50% or less. Patients received either a CRT pacemaker or implantable cardioverter defibrillator (the latter assuming a need for defibrillation) and were randomized to standard right ventricular pacing or biventricular pacing within those two main arms. The article says that of the 918 enrolled, 691 underwent randomization and were followed for an average of roughly three years.

"The primary outcome occurred in 190 of 342 patients (55.6%) in the right-ventricular-pacing group, as compared with 160 of 349 (45.8%) in the biventricular-pacing group," the abstract says. Patients randomized to biventricular pacing "had a significantly lower incidence of the primary outcome over time than did those assigned to right ventricular pacing" only, the authors state, an effect they say extended to the ICD group as well. Complications associated with LV lead implant occurred in 6.4% of patients.

Curtis, the principal investigator in Block HF, told MDD the NEJM report "is of the primary results of the trial," but that more reporting will ensue, "probably for the next couple of years." When asked whether the data as they stand indicate a difference in benefit between class I, II and III patients, Curtis said the data have not yet been broken down that far, but she noted "the majority of patients were either unchanged or improved."

It appears that slightly more than 200 enrollees were not randomized, and Curtis said the principal driver of this was disqualification for degree of atrioventricular block. "The physician performed an AV node conduction test at time of implant," Curtis said, a test deemed failed if "they still conducted one-to-one even at heart rates up to 100."

"If the patient exhibited second-degree AV block below 100 beats, they were eligible," Curtis noted, but 95 of those enrolled did not pass the AV block test, with the remainder lost to the trial for "a smattering of other reasons" such as withdrawn consent.

Curtis said study site effect was not particularly apparent, and that the benefits of biventricular pacing were apparent "across the board." She also indicated that lead placement was not an apparent issue. "Most right ventricular leads were placed in the apex," she said, adding that left ventricular leads were generally placed laterally or posterolaterally." "We didn't exclude anybody" over lead location, she said, adding that prior studies of LV lead placement suggest that "lateral or posterolateral were the best locations, so I would expect that" to hold for leads placed in the trial.

Regarding whether right ventricle pacing only creates problems due to dyssyncrhony of the left ventricle, Curtis indicated that this is a pretty widely accepted idea. "People have started believing it enough that . . . they didn't want to enroll their patients in the study" due to the prospect of their patient ending up in the RV pacing arm only, she remarked. "That's why I'm glad we got it done when we did," she said.

Curtis indicated there are still questions about biventricular pacing for other populations. "What we don't know . . . is if you have an absolutely normal (left ventricular) ejection fraction, is there a potential for problems with RV pacing?" This patient group was not enrolled, however, so "we can't say the results [of Block HF] pertain to those patients."

The coverage/reimbursement question is still out there, and Curtis said it's tough to forecast how the Centers for Medicare & Medicaid Services might respond. She noted that Medtronic is preparing a filing for FDA, but "until there is an FDA-approved indication, I don't know how CMS would react."

When asked whether the Block HF data indicated a difference in outcomes for women and men, Curtis said, "we have not analyzed that yet," but she remarked that in general terms, "one reason why women often respond better [to CRT] is that ischemic cardiomyopathy – where there's scar tissue – is more likely in men." She pointed out that scar tissue doesn't respond well to pacing, but dilated cardiomyopathy, in which a patient's heart tissue is generally viable, responds fairly well to pacing. Curtis also pointed out that women "are more likely to have dilated cardiomyopathy than men."

"Even when we control for those factors, we tend to see women do better in terms of hospitalization and death than men" under resynchronization generally speaking, Curtis said.

Medtronic indicates it will complete the application by the end of the year, but that no date has been set yet for the accompanying advisory hearing.

Mark McCarty, 703-361-2519

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