Could Earlier Be Better for LVAD Placement?

The majority of left ventricular assist device (LVAD) implantations have been performed in advanced heart failure patients who are hospitalized and dependent on intravenous inotropic drugs. But what if the option of earlier LVAD placement were offered to patients who weren’t yet inotrope-dependent but still met clinical guidelines for LVAD implantation?

The question is a salient one for heart failure specialists. “When a patient who’s on inotropic therapy in the ICU asks if they’re going to die if they don’t go ahead with an LVAD, the answer, unfortunately, is probably yes,” says Randall Starling, MD, MPH, Head of Cleveland Clinic’s Section of Heart Failure and Cardiac Transplant Medicine and Medical Director of its Kaufman Center for Heart Failure.

His colleague Nader Moazami, MD, adds that patients too often “feel their back is up against the wall” when it comes to deciding about an LVAD. “Once they’ve reached that point, it truly has become a life-and-death decision,” says Dr. Moazami, Surgical Director of the Kaufman Center for Heart Failure and Director of the Cardiac Transplantation and Ventricular Assist Device Therapy Program.

A groundbreaking look at earlier intervention

Drs. Starling and Moazami recently took part in a big step toward an answer to this question of early LVAD use as key researchers in a first-in-kind study called ROADMAP (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management). Findings from the prospective, multicenter, controlled investigation were recently published in the Journal of the American College of Cardiology, and they provide support for earlier LVAD use than has been traditional.

ROADMAP included 200 ambulatory heart failure patients from 41 U.S. centers, with Cleveland Clinic as the lead enrolling center. All patients had New York Heart Association functional class IIIB/IV disease and met indications for LVAD destination therapy, but they were not dependent on inotropic therapy. Additional inclusion criteria were hospitalization for heart failure at least once during the prior year and inability to walk more than 300 meters in six minutes. The observational study aimed to compare outcomes between the 97 patients who received an LVAD and the 103 patients who received optimal medical management.

“We wanted to know how patients with heart failure who are less ill fare when an LVAD is implanted earlier,” explains Dr. Starling, who served on the steering committee that designed the study. “Overall, they did very well, with one-year survival rates similar to those for patients receiving optimal medical management, and with only a 1 percent risk of dying from LVAD surgery. That’s one of the lowest surgical mortality rates in any LVAD study. LVAD recipients also had better functional outcomes and greater improvements in quality of life and depression than those who were treated medically.”

The study’s primary composite end point was survival on patients’ original therapy with improvement in six-minute walk distance of 75 meters or greater at 12 months. More patients met that end point in the LVAD group than in the medical management group (39 percent vs. 21 percent; OR = 2.4 [95 percent CI, 1.2 to 4.8]) — even though patients in the LVAD group were more severely ill at baseline.

The average hospital stay following LVAD implantation was 17 to 18 days. “When patients come to us more electively — when they aren’t in the ICU on inotropes or a balloon pump — they get through surgery easier,” observes Dr. Moazami.

Adverse events higher but largely manageable

The main limitation of LVAD therapy in ROADMAP was an adverse event rate about twice as high as that in the medical management group (1.89 vs. 0.83 events per patient year).

Adverse events in the LVAD group were primarily driven by bleeding, especially GI bleeding. Dr. Moazami notes that the vast majority of bleed-related events were nonfatal, treatable and manageable, with the exception of stroke.

“It’s also important to remember that whether patients are really sick or not as sick, adverse events will still happen,” Dr. Starling says. “The bottom line is that less-ill patients do well, and less-ill patients may experience adverse events. With LVAD therapy, it’s about finding the balance between improved survival and quality of life and the potential for adverse events.”

Individualizing the LVAD decision

An accompanying commentary on the ROADMAP study in the Journal of the American College of Cardiology refers to the idea of earlier LVAD placement as “a highly preference-sensitive decision” with “a number of risk-benefit tradeoffs among mortality, adverse events and functionality that require robust clinician-patient dialogue early in the course of patients’ illnesses.”

Dr. Moazami concurs, noting that ROADMAP helps turn a previously urgent life-and-death choice into “more of an individualized decision” for patients who are still very ill. “It really comes down to what they want their life to be like,” he says. “If they have a miserable life sitting in a chair all day and can’t catch their breath, they may feel the potential benefits of earlier LVAD therapy outweigh the risk of adverse events.”

Cleveland Clinic patients who are considering LVAD placement receive in-depth counseling and a thorough workup to help make that decision and determine if they are good candidates. “There’s a prolonged educational process,” Dr. Moazami says. “We want to ensure that LVAD therapy is right for the patient, and we also involve their family.”

A bright road ahead

The ROADMAP researchers are continuing to follow study participants and expect to report 24-month results at a major clinical meeting during the first half of 2016.

Meanwhile, as experience with LVADs mounts and newer generations of devices come to market, the risk of adverse events from LVAD therapy will likely diminish, which could make earlier intervention an even easier decision, Dr. Starling says. Cleveland Clinic is currently participating in a clinical trial of one of those newer devices.

“The future of LVAD therapy is becoming brighter,” Dr. Moazami adds. “The technology is getting better, and we’re gaining a better understanding of the therapy’s limitations and how to handle them. It’s a great therapy now, and it will likely be fantastic several years from now.”