BOSTON – Positive results from a confirmatory trial appear to put the Optimizer by Impulse Dynamics, a cardiac contractility modulation (CCM) device for patients with function-limiting heart failure, on track for imminent U.S. marketing approval by the Food and Drug Administration. If that happens, several hundreds of thousands of U.S. heart failure patients would immediately become candidates for this treatment based on the enrolled study populations, the benefits shown, and current treatment options for advanced heart failure, experts predicted.

That’s because the heart failure patients targeted in the confirmatory study have no other device-based treatment options, unlike similar heart failure patients with a wider QRS duration and a lower ejection fraction. The patients targeted in the study had New York Heart Association functional class III or ambulatory class IV disease, a relatively short QRS duration of less than 130 milliseconds, and a left ventricular ejection fraction of 25%-45%. More specifically, the subgroup of enrolled patients with an ejection fraction of 35%-45% saw the greatest benefit from the device: They did best in the subgroup analysis of the FIX-HF-5C (Evaluate Safety and Efficacy of the OPTIMIZER® System in Subjects with Moderate-to-Severe Heart Failure) trial.

CCM “promises to meet a very large unmet need in heart failure,” William T. Abraham, MD, said as he presented the confirmatory study’s results at the annual scientific sessions of the Heart Rhythm Society. ”These patients aren’t doing well, but don’t qualify” for a heart transplant, left ventricular assist device, implantable cardioverter defibrillator, or cardiac resynchronization therapy (CRT), noted Dr. Abraham, professor and director of cardiovascular medicine at the Ohio State University in Columbus. In the months following the anticipated FDA approval, Dr. Abraham said he expects the device will be implanted in tens of thousands of U.S. heart failure patients who match the criteria of those who got the biggest benefit from CCM.

“There are few if any evidence-based treatments for patients with an ejection fraction of 35%-45%. This is an underserved population, so the potential of CCM is appropriately high,” Dr. Abraham said.

“The results make a big case for going ahead with the device. Electrophysiologists will need to understand what this translates into in clinical practice, but learning about the implant strategy is straightforward,” commented Jagmeet P. Singh, MD, PhD, a professor of medicine at Harvard Medical School and associate chief of cardiology at Massachusetts General Hospital, both in Boston. “This is a population that can benefit from this device.”

Researchers designed the study in consultation with the FDA to resolve lingering regulatory concerns following completion of three prior randomized trials with a total of nearly 650 patients. Dr. Abraham simultaneously reported the results at the meeting and published them in a report (JACC Heart Failure. 2018 May 10. doi: 10.1016/j.jchf.2018.04.010); these results from 160 patients – 74 of whom received the device and 86 of whom continued medical therapy – showed the superiority of the device for the primary endpoint of change in exercise capacity (as measured by peak oxygen uptake) and for the secondary endpoints of quality of life (as measured with the Minnesota Living With Heart Failure Questionnaire) and functional status (as measured by New York Heart Association class). The boost in exercise capacity, an average increase of 0.84 ml/kg per min in peak oxygen uptake after 24 weeks, “was similar to the improvement seen with CRT in patients with a wide QRS interval” who thereby qualified for CRT placement, Dr. Abraham said.

The CCM device also met the study’s prespecified safety endpoint of a complication rate of less than 30% – with an actual rate of 10%. “The complications were those we expect from implanted leads and pulse generators and were comparable to what happens with other implanted rhythm devices. In the context of the benefits patients received and their having no other treatment options, I see the complication rate as acceptable,” Dr. Abraham said during his report.

“The investigators are to be complimented for their meticulous measure of exercise. This truly was a well-done trial with an exercise endpoint,” commented designated discussant for the new report Lynne W. Stevenson, MD, a professor of medicine and an advanced heart failure specialist at Vanderbilt University in Nashville, Tenn.

In summing up the trial’s results, Dr. Stevenson noted that “the safety endpoint was met, the primary endpoint and other functional endpoints were met, and functional endpoints are of vital importance to patients. The CCM story is not yet the CRT story,” with CRT having produced even larger effects in its pivotal trial, also led by Dr. Abraham (New Engl J Med. 2002 June 13;346[24]:1845-53), cautioned Dr. Stevenson. But in general she put a positive spin on the CCM device, saying that it “has ingenuity and innovation, and we look forward to a better understanding of which patients benefit from CCM and what we can tell them about the magnitude and duration of the benefit.”

“With CRT, we have a patient phenotype to treat that makes sense – patients with a very wide QRS duration, and [CRT] has stood the test of time. Is CCM truly additive, and does it provide a benefit that nothing else can give you?” asked Clyde Yancy, MD, professor and chief of cardiology at Northwestern University in Chicago. “We can’t give every patient everything. We need to figure out who are the right patients” for CCM treatment, Dr. Yancy said in an interview.

The FIX-HF-5C trial was sponsored by Impulse Dynamics, the company developing the CCM Optimizer device. Dr. Abraham has been a consultant to Impulse Dynamics, as well as to Abbott Vascular, Medtronic, Novartis, and St. Jude Medical. Dr. Singh has been a consultant to Biotronik, Boston Scientific, Liva Nova, Medtronic, and St. Jude. Dr. Stevenson has received research funding from Abbott and Novartis. Dr. Yancy had no disclosures.

mzoler@mdedge.com

SOURCE: Abraham W et al. Heart Rhythm 2018, Abstract B-LBCT01-02.

FDA approval expected for CCM in heart failure patients