Now that continuous-flow left ventricular assist devices (LVAD) are available as a destination therapy, rather than just a bridge-to-transplant therapy, options for late-stage heart failure patients have expanded. The new indication is welcome news, but the debate has begun regarding which patients are the best candidates, and when in their care cycle to implant LVADs.
More days are spent in the hospital for care of patients with heart failure than any other diagnosis. The disease commonly progresses and becomes refractory to current treatments. Medical management may improve clinical status in the short term, but survival rates at five years average only 40 percent and mortality may be as high as 80 percent in one year in the most advanced stages. Cardiac transplantation is available for only a minority of patients—about 2,000 annually—because of the lack of suitable donor hearts.
In the 2001 landmark REMATCH trial, the first study to investigate the use of mechanical circulatory support as an alternative to medical therapy in advanced heart failure, Rose et al found that the pulsatile-flow HeartMate XVE (Thoratec) device reduced mortality rates by 48 percent compared with medical therapy in patients not eligible for transplantation. Despite the dismal survival rate in the control arm (25 and 8 percent at one and two years, respectively), researchers said the rate for the device arm was suboptimal: 52 and 23 percent at one and two years, respectively (N Engl J Med 2001;345(20):1435-1443).
“We believe that our findings establish new standards for survival, quality of life and adverse events,” Rose et al wrote. “The limitations we found clearly justify an intensification of efforts to improve both these devices and patient care, with the goal of improving outcomes in the sickest of patients and paving the way for an assessment of the use of mechanical circulatory assistance in patients with serious, but less severe heart-failure syndromes.”
In 2002, the FDA approved the HeartMate XVE device for destination therapy. Prior to this, the devices were predominantly used as intermediate term support for bridge-to transplant therapy. LVAD technology has steadily advanced, becoming smaller and more durable by changing from a pulsatile design to a continuous-flow design. In January, the FDA expanded the indications for the HeartMate II continuous-flow device from bridge-to-transplant to include permanent use or destination therapy. It is the first continuous-flow device approved for this indication.
Part of the problem with the older-generation devices is that they are more bulky and less durable then current-generation devices, says Leslie Miller, MD, chair of cardiovascular medicine at Washington Hospital Center in Washington, D.C. At 18 months, about 50 percent of the first-generation LVADs had to be extracted and exchanged.
The HeartMate II’s smaller size should allow its implantation into more patient populations, such as women and men of smaller stature, says Jeffrey Shuren, MD, director of the FDA’s Center for Devices and Radiological Health.
The FDA says that the approval of the HeartMate II as a destination therapy was primarily based on results from the HeartMate II Destination Therapy (HMII) trial, a randomized, controlled study of 200 participants at 38 centers (134 with HeartMate II, 66 with HeartMate XVE). Slaughter et al found that 46 percent of participants with the continuous-flow LVAD, compared with 11 percent in the control arm, survived with no disabling stroke or need for device replacement at two years. The need to replace or repair the LVAD occurred in 36 percent of patients in the control arm compared with 10 percent in the continuous-flow group, a similar rate to the earlier REMATCH trial (N Engl J Med 2009;361(23):2241-2251).
Who and when?
As advancements in technology widen patient options, the discussion about patient eligibility continues to evolve. “The pendulum has moved away from the critical, multiple organ failure candidates to less severe cases of advanced heart failure,” Miller says. Preliminary data have shown that patients with advanced, but less severe heart failure have improved survival and shorter hospital stays when implanted with the device.
Despite the positive findings of HMII, lead author Mark