Initially approved by the Food and Drug Administration (FDA) for a bridge-to-transplant indication, the continuous-flow HeartMate II left ventricular assist device (LVAD) was recently approved for destination therapy for patients with chronic advanced heart failure (HF). These patients are typically older, frequently have a higher comorbidity burden, and are not eligible for cardiac transplantation. As Ulrich P. Jorde, MD, and colleagues point out in a recent JACC article, "real-world" destination therapy (DT) candidates have more treatment complexities than patients in a strictly regulated clinical trial setting. Are the levels of success found in the earlier HeartMate II study replicable and achievable in commercial use?

To fulfill FDA requirements for a post-approval (PA) study, Jorde et al. conducted a prospective evaluation of the first 247 HeartMate II patients identified pre-operatively for DT in the national INTERMACS registry. Their outcomes were compared with a historical comparison group of 133 patients enrolled in the primary data cohort from the pivotal trial in which the continuous-flow device proved superior to pulsatile-flow support for DT. The researchers also determined INTERMACS profiles for the PA group: 47% of patients were INTERMACS profile 1-2 (representing the sickest patients in critical cardiogenic shock and progressive decline on inotropic support), and 29% were profile 3 (representing stable but inotrope-dependent HF).

Median duration of support in the PA group was 2.0 years, versus 1.7 years in the trial group. One- and 2-year survival rates were higher in the PA group (74±3% and 61±3% vs. 68±4% and 58±4%). Within the PA group, survival rates were impacted by degree of disease (based on INTERMACS profiles), with healthier patients predictably surviving longer (1- and 2-year survival rates):

• INTERMACS profiles 4-7 = 82±5% and 67±6%
• INTERMACS profiles 1-3 = 71±3% and 59±4%

The percentage of patients reaching the endpoint of survival free from any stroke and reoperation to replace the device at 2 years in the PA group was 54% (135/247), compared to 44% (58/133) for the trial group (p = 0.042). Median length of stay after surgery was 6 days shorter in the PA group (21 vs. 27 days). Patients in both groups demonstrated similar degrees of improvements in functional status and quality of life.

Adverse event rates in the PA group were similar or lower than in the trial group, including significant improvements in rates of device-related infection (19% vs. 35%; p < 0.001) and bleeding requiring packed red blood cells (54% vs. 81%; p < 0.001) or re-exploration (13% vs. 30%; p < 0.001). PA patients also experienced fewer strokes (11.7% vs. 19%; p = ns).

Not only did the performance results with the HeartMate II device in the PA study match those observed in the initial trial, but they demonstrated a more favorable trend than the trial results. "Our results with 2-year survival of 61% in the overall cohort and 67% in less-sick patients clearly indicate that the hurdle of providing survival benefit has been more than taken by currently available technology," the investigators concluded. "While it is clear that further improvement in survival should occur, and further reduction in serious adverse events must occur, to make LVAD therapy the right choice for less sick heart failure patients, our data reflect the state-of-the-art and as such set the bar for all future endeavors in circulatory support as destination therapy."

Jorde UP, Kushwaha SS, Tatooles AJ, et al. J Am Coll Cardiol. 2014;63:1751-7.