番茄社区

BOSTON -- A novel implanted electrical device to strengthen heart contractions improved exercise performance and other outcomes in heart failure patients in the 25% to 45% ejection fraction (EF) range, a confirmatory study showed.

The Optimizer device for cardiac contractility modulation (CCM) improved maximal aerobic capacity, with a significant 0.84-ml/kg/min greater VO₂ max at 24 weeks than seen with medical management alone in the FIX-HF-5C trial.

That difference in these narrow, less than 130 ms QRS patients was on par with what has been seen with cardiac resynchronization therapy (CRT) in wide QRS intervals, and it was even greater in the group of patients with EF in the 35% to 45% for whom there are currently no guideline-directed therapies, William Abraham, MD, of Ohio State University Wexner Medical Center in Columbus, reported at a late-breaking clinical trial session here at the Heart Rhythm Society meeting.

The relative 11-point improvement in quality of life on the Minnesota Living with Heart Failure score was roughly twice what drug therapy can achieve and is on par with CRT, he added. The findings were simultaneously published in .

"It promises to meet a very large unmet need in the management of heart failure," Abraham said at a press conference at the meeting. "About four million [Americans with symptomatic heart failure] have reduced ejection fraction -- anything below 45%. At any time among those patients, about 30-40% are categorized in New York Heart Association [NYHA] functional class 3 or ambulatory class 4, and that's despite all available guideline-directed drug and device therapies."

Regulatory approval may be "in the hands of others," but Sanjeev Saksena, MD, of Rutgers University Robert Wood Johnson Medical School in New Brunswick, NJ, and a past president of the Heart Rhythm Society, who was not involved with the study, told 番茄社区 that the device is a treatment he wants available for his patients.

"These are groups of patients we have very little to offer at this point, beyond heroic measures like assist devices," he said.

Previously, the FIX-HF-5 clinical trial showed the CCM strategy as safe but not meeting the primary efficacy endpoint of ventilatory anaerobic threshold on cardiopulmonary exercise stress testing in NYHA functional class III or IV symptoms and a site-determined EF of 35% or less.

The FDA required the new confirmatory trial under the agency's expedited review process for the rechargeable device, which provides non-excitatory electrical signals via two leads in the right heart during the cardiac absolute refractory period. The mechanism of action is not heartbeat initiation, but rather a way to load the cells with calcium to induce a more forceful contraction.

The trial included 160 patients with heart failure, a QRS interval less than 130 ms, and an EF of 25-45%, randomized to CCM for 5 hours per day for 6 months or to medical therapy alone.

Notably, the trial's primary endpoint shift from anaerobic to aerobic exercise capacity was a shift to a less subjective, more effort-dependent endpoint, noted the discussant for the study at the meeting, Lynne Stevenson, MD, of Vanderbilt University Medical Center in Nashville.

Abraham argued, though, for the "extensive efforts to avoid bias in exercise performance," with onsite training for standardization of exercise testing, feedback to sites on study quality from the core lab, retest requests for inadequate studies, two tests performed at each time point, and blinded core lab reading.

When the two trials' relevant patients were combined, there was a significant reduction in cardiovascular death and heart failure hospitalizations compared with controls, with a nearly 4-day advantage in days alive outside the hospital.

While the device outcomes met a "high bar," Stevenson concluded, "I don't think the CCM story is yet the CRT story."

The complication rate of 10.3% met the primary safety performance criterion in the Bayesian analysis, which Abraham said generally included complications that would be anticipated with leads and pulse generators. "Taken in the context of risk-benefit, though, particularly to these patients -- who I want to emphasize have no other options for treatment when they remain in class III-ambulatory IV despite current guideline-directed medical therapies -- I would view [the complications] as acceptable."

Comment