By Mark McCarty, Regulatory Editor

Some devices are just the latest and best in class while others force clinicians to revisit long-held assumptions about the possibilities of a device type. This appears to be the case with an interim report of data from a study of the Heartmate 3 device, which not only handily bested the Heartmate II for freedom from disabling stroke at two years, but also prompted one observer to ask whether the time has come to try a left ventricular assist device against transplantation.

Mandeep Mehra of Brigham and Women’s Hospital in Boston presented data for 366 patients enrolled in the Momentum 3 (Multi-Center Study of MagLev Technology in Patients Undergoing MCS Therapy with Heartmate 3) study, which commenced enrollment in September 2014 with a target total enrollment of 1,028. The study matches the Heartmate 3 device made by Thoratec of Pleasanton, Calif. against the previous iteration, the Heartmate II. Thoratec was part of St. Jude Medical when the latter was absorbed by Abbott in early 2017.

The study, which randomized enrollees in roughly equal proportions to each device, is still underway at 69 centers in the U.S., and the median age for the 366 patients reported at this year’s annual meeting of the American College of Cardiology is 60 years. Of this group, 78 percent were men, and 85 percent were on intravenous medication for heart failure due to intolerance of oral forms or loss of efficacy. The FDA approved the device in August 2017 for patients with late-stage heart failure as a bridge-to-transplant device.

The primary endpoint is a combination of disabling stroke, death from heart failure, and device malfunction requiring surgery for replacement or removal. Nearly 83 percent on the study article were still alive at two years compared to 76.2 percent on the legacy device, and only one percent of patients on the newer device needed surgical revision for any cause compared to 17 percent for the Heartmate II. Of that latter group, 12 cases were for pump thrombosis. The study appears in the March 11 online issue of the New England Journal of Medicine under the title, “Two-Year Outcomes with a Magnetically Levitated Cardiac Pump in Heart Failure.”

Newest device mimics natural pulse Mehra said the Heartmate 3 is small enough to be implanted directly in the chest whereas the antecedent required formation of a pocket in the abdomen to accommodate the device. He stated also that “the blood flow pathway is wider in the Heartmate 3, which may contribute to the reduction in pump thrombosis,” but the device also includes a governor that varies the rotational velocity of the pump in order to mimic the body’s natural pulse, which may in turn help prevent a build-up of blood inside the device. The impeller mechanism in Heartmate 3 is radially mounted in contrast to the in-line rotor pump seen in the Heartmate II.

Patient characteristics varied somewhat, with 9.5 percent of the Heartmate 3 group undergoing valve replacement or repair, a statistically significant difference compared to the four percent on the Heartmate II. Diuretic use also varied to a degree deemed statistically significant, and each arm of the study included patients for bridge to transplant, bridge to transplant candidacy, and destination therapy. Destination therapy was easily the most numerous group in both arms.

For the intent-to-treat population, two-year survival without disabling stroke or device-driven reoperation was 77.9 percent on the Heartmate 3 and 56.4 percent on the control device, hitting statistical significance for superiority. Overall survival favored the study article without reaching statistical significance, (82.8 percent compared to 76.2 percent for Heartmate II), while freedom from disabling stroke for those still alive at 24 months was a statistical wash via a 0.3 percent absolute difference.

The Heartmate 3 distanced itself from its antecedent in freedom from reoperation at 97.2 percent compared to 75.5 percent, and Mehra noted that two thirds of the Heartmate II reoperations were undertaken to address pump thrombosis or severe hemolysis. The number of disabling strokes for the entirety of the 366 patients was double in the Heartmate 3 arm (six, compared to three for Heartmate II), although the older design was associated with 24 non-disabling strokes, four times the number seen in the group receiving the Heartmate 3.

Mehra reminded those in attendance that LVADs “have been in play for almost 50 years with multiple shifts in technology.” Despite substantial iteration, quality of life is far short of optimal, and the latest in the Heartmate series offers minimal destruction of red blood cells, in part because the use of magnetic levitation eliminates the need for mechanical bearings. Mehra said the Heartmate II had performed as expected, turning in numbers similar to those seen in registries and other clinical studies.

James Januzzi, a cardiologist at Harvard and the associate editor of the Journal of the American College of Cardiology, said Momentum 3 is an “elegantly executed and very much needed study.” He said the need to balance the risks of stroke and hemorrhage is still something of a high-wire act for cardiologists, adding, “with this new technology, we’ve addressed an unmet need.”

“It really brings forward the question,” thanks to the 82 percent survival rate at two years, “if we should be thinking about a comparison to transplant, because now we have a safer alternative” to earlier LVADs, Januzzi said.

Januzzi said the numbers should be reassuring in terms of device use for destination therapy, but he also said, “I think this is going to open the gates for more referrals and more opportunities” for transplant. Januzzi said the notion of trying the Heartmate 3 against transplantation is worth considering if only due to the shortage of available transplants, although some healthier heart transplant candidates may feel uncomfortable at the prospect of taking a transplant from a sicker patient who is in more dire need.

Mehra said it is not uncommon for patients to wait three years for a transplant, but both Mehra and Januzzi said a single-arm study with matched controls might be a feasible, if difficult approach. Mehra said in a single-arm study, “we don’t address both sides of the ventricle,” but Januzzi said the Momentum 3 study tells cardiologists that “individualizing which patient should get which therapy is something we should think very carefully about.”