Heart Failure Treatments Widen with Continuous-Flow Assist Devices
What’s changed?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 S. Slaughter, MD, director of cardiac surgery research at Advocate Christ Medical Center, Oak Lawn, Ill., says the trial does not directly address when in the continuum of care a heart failure patient should be referred for device implantation. That is the crux of the current debate, because even his colleagues aren’t in agreement. HMII co-author Reynolds M. Delgado, III, MD, medical director of mechanical assist devices in heart failure at the Texas
Heart Institute in Houston, says that the patient selection methodology employed by the HMII researchers provides a good model for clinical practice.
Investigators enrolled patients using the following criteria: a left ventricular ejection fraction of less than 25 percent; a myocardial oxygen consumption (MVO2) of less than 14 ml/kg of body weight per minute, or less than 50 percent of the predicted value; and NYHA Class IIIB or IV symptoms for at least 45 of the 60 days before enrollment or dependence on an intra-aortic balloon pump for a period of seven days or inotropes for a period of at least 14 days before enrollment.
“Those patients with NYHA Class IV symptoms, despite receiving medical therapy and adhering to diet restrictions, are potential candidates,” says Delgado, who adds that the MVO2 test also is used to predict mortality in heart failure. “If the MVO2 test is less than 14, those patients are generally transplant or LVAD candidates,” he says.
Slaughter is less certain. “While there are lots of triggers and symptoms that may lend themselves to referrals, there are no concrete indications in less ill patients,” he cautions.
Yet, Miller says there are more than 100,000 patients with advanced heart failure who could benefit from these devices in the U.S. He has witnessed an increase in referrals over the past few months, which he attributes to the HMII study, and he expects those numbers to rise even more since the FDA decision.
“The numbers of implants will increase—and while it won’t be exponential—it will be persistent and gradual, in tandem with a continued expansion of the field,” Slaughter says. “With the improvement in survival and quality of life, along with decreased adverse events, this clearly has become an appropriate standard of care therapy for patients with advanced heart failure.”
“Under the current paradigm, we still get patients referred far too late in the care continuum—often times, too late. If we received these patients six months to a year prior, they could survive and have a better quality of life,” Slaughter says.
In the accompanying editorial to HMII, James Fang, MD, from University Hospitals Case Medical Center in Cleveland, suggests the results should change clinical practice today. “The first priority would be to make sure patients and physicians are aware that ventricular assist device therapy is available, effective and safe for well-selected patients,” he wrote. “Second, we should not delay referral until surgical morbidity and mortality become prohibitive” (N Engl J Med 2009;361:2282-2285).
The REVIVE-IT trial will deliver some answers as it is designed to assess which patients with less severe heart failure would most benefit from assisted circulation devices, and when would be the most appropriate time to intervene.
Surgeon/center considerations“The practices and surgeons who are currently performing these procedures are very familiar with long-term outcomes, potential complications and overall costs,” says Slaughter. He adds that issues have arisen when the procedures are not performed in Centers of Excellence.
Miller points out that the amount of time required for surgery with the new continuous-flow device is less—as it is one-fifth the size of its predecessors—meaning the peri-operative risks associated with the device are also fewer.
To receive reimbursement and accreditation, CMS and the Joint Commission require facilities to perform 10 procedures over three years. After that, there is no stated minimal volume, until the facility needs to become re-approved.
Lietz et al found a significant correlation between center volume and survival, with caveats (Circ Heart Fail 2009;2(1):3-10). Researchers reviewed the Thoratec Destination Therapy Registry, using the HeartMate XVE from July 1998 through December 2005. Facilities that performed less than four implants a year had worse one-year survival rates than those that performed more than nine (47 percent vs. 67 percent).
However, volume was not an independent predictor of one-year survival when adjusted for the pre-operative destination therapy risk score, suggesting that other factors, such as improved candidate selection, may have accounted for the institutional learning curve, according to the authors.
Slaughter, who co-authored the Circulation study with Lietz, says that LVAD implant volume at heart transplant centers has increased. Currently, there are fewer than 20 percent of U.S. LVAD programs performing more than 35 procedures per year, but the number of centers performing higher volumes of implants is predicted to increase. Also, Slaughter does not advocate for non-transplant centers to begin implanting LVADs without any previous experience or without experienced surgeons onsite.
From a provider perspective, follow-up monitoring is “relatively light,” especially compared with monitoring NYHA Class IV heart patients, Delgado says. Also, following the procedure, patients are only required to take an aspirin and a moderate dose of Coumadin.
Economic considerationsWhile Delgado concurs that the HMII study and the recent FDA approval will cause LVADs as a destination therapy to experience an uptick in referrals, he says the one caveat could be the “uncertain reimbursement environment, which is not always dictated by logic and science. Right now, the reimbursement barely covers the device’s cost.”
Delgado says the field would benefit from a comparative effectiveness trial, which also would be useful in convincing hospitals and health systems to use the technology. The providers need to buy into the program, as they need to purchase both the hardware and the support services, he says.
“In the absence of cost-effectiveness research, everyone focuses on the cost of the device, but those analyses overlook the costs associated with not receiving these devices,” says Slaughter. “We spend a lot of money already to do practically nothing.”
At AHA.06, Russo et al presented the calculated mean cost of medical management in the final two years of life among end-stage heart failure Medicare patients, which was $161,154, with 51.5 percent occurring in the final six months. The uncensored mean two-year total cost was $201,227, with 48.4 percent expended in the final six months (median: $71,353). Costs in the last six months were higher among patients who died as inpatients ($95,332) versus outpatients ($79,513) or in hospice ($55,517).
In addition to these expenses, Miller, who co-authored the AHA presentation, says that these “people had a terrible quality of life, due to being highly symptomatic.”
Overall, Russo et al found that $16 billion to $20 billion in U.S. medical resources are consumed in the final two years of life for this patient population, including $8.3 billion to $9.7 billion in the last six months. They concluded that “aggressive medical management alone offers limited value for expense incurred […and] alternative management strategies that improve outcomes, minimize suffering, and/or reduce expenditures should be explored.”
Based on the most recent AHRQ data, these expenses are not going away because hospitalizations for congestive heart failure rose by 3 percent to more than one million in 2007, becoming the second most common disease treated in hospitals.
“By one estimate, heart failure accounts for 5 percent of all healthcare costs in the U.S.,” Delgado says.
The goal ultimately is to have a quality of life years saved of less than $100,000, Slaughter says. If we reach this goal, it is clearly competitive with other advanced therapies. He cites data that will soon emerge showing cost savings of approximately 50 percent with LVADs as a destination therapy. “Even if the cost is equivalent, it seems intuitive to give the patient a chance to prolong life along with improved quality,” he says.
“As an alternative to heart transplant or destination therapy, these new pumps are capable of running for 10 years, without failure, and they can have it replaced if needed, with no biologic contact or interface because it’s magnetically suspended. We think this is going to be an extraordinary treatment option for patients with advanced-stage heart failure patients,” Miller states.