|
More demand than donors All respondents agree that the greatest challenge for patients facing heart failure is the shortage of donor hearts for transplant. Since the start of the National Heart, Lung and Blood Institute’s “Artificial Heart Program” in 1964, mechanical devices for long-term implantation to support cardiac function have evolved to a point where they are a viable alternative for patients with advanced heart disease and cardiac failure. While heart transplant (HTx) remains the gold standard for these patients, with 1-year survivorship of 85-90%, and patients surviving for up to 25-30 years post-transplantation, the chronic shortage of donor hearts meets the needs of only 10-30% of patients. In addition, only about 30% of donor hearts are accepted for transplantation [Stanford Paper]. For example, recent data reports that in Germany, there were 286 transplants for 790 patients (2015). Making matters worse, the demographic shift in developed markets toward older patients indicates that the number of potential recipients with heart failure is expected to grow much more rapidly than the growth in youn g healthy eligible donor hearts. With this gap expected to increase, the options available for heart failure patients include a variety of Mechanical Circulatory Support (MCS) devices. Can the mechanical devices intended to assist or replace a patient’s cardiac function while they await a donor heart for implantation, help reduce or even eliminate this shortage? |
Participants TMTG interviewed leading cardiac care clinicians specializing in heart failure to understand the current state-of-the-art in treatments for patients suffering from heart failure. Participants include:
|
Current State-of-the-art, devices and challenges
Devices range from the most common Left Ventricular Assist Devices (LVADs) to the less common Total Artificial Heart (TAH). Globally, current leading technologies approved for implantation include Medtronic’s Heartware and Abbott/StJude/Thoratec’s HeartMate ventricular assist devices (VADs) and the Syncardia Total Artificial Heart (TAH). These d
evices may support heart function temporarily as a Bridge-To-Therapy (BTT) until a transplant becomes available or, increasingly, as a Destination Therapy (DT). As tracked in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) of FDA-approved MCS devices, current generation devices are being implanted at a rate of about 2500 implants per year plus those devices enrolled in ongoing clinical trials. Overall survival is over 80% at one year and 70% at two years.[2017 INTERMACS] One and two-year survival with latest generation LVAD devices (HeartWare in ReVOLVE trial, HeartMateIII) is now comparable to heart transplant at up to two years. [Interviews, and Kirklin JK, Naftel (23 from Prinzing JTD article)] As physicians achieve constantly improving surgical success and their patients show improved quality of life and lengthening survivorship, the strategic distinction between BTT and DT has begun to disappear. Currently, over 50% of continuous flow implants are implanted with a strategy of DT [2017 INTERMACs].
“[Total artificial heart] is pretty obsolete in its current available form. It's still very similar to the first Jarvik heart Mr. Clark got. I do not use it any longer.” - Yoshifumi Naka, MD
While most surgeons view VAD as the best alternative to HTx for most patients, there remain indications for Total Artificial Hearts (TAH). At less than 2% of circulatory support device implantations (Compared to nearly 25,000 VADS, a total of about 400 TAH have been implanted), surgical complications during transplant and total failure of the heart (both left and right) may counterindicate the use of an LVAD and require the need for a TAH implantation.
According to Dr. Francisco Arabía, since the reported LVAD outcomes are better, people assume they are better for everyone, but this is a fallacy. The LVAD companies promote their devices as the one appropriate solution, but LVAD indications tend to select candidates from InterMACS Profile 3 or 4 patients, those that have functioning right ventricles and overall better health. However, InterMACS Profile 1 and 2 patients, the sickest, are more often selected as candidates for the TAH. Those sicker patients with failing left and right ventricles most often cannot be treated adequately with an LVAD. While LVADs will meet the needs of the 70+% of heart failure patients with left ventricular disease, up to 30% of patients need biventricular total heart support. Their alternatives if no donor heart is available include either two LVADs, or a TAH. While currently approved LVADs are reliable, with fatal device malfunction occurred in only 3.5% of implantations [Prinzing, JTD], current adverse events include device thrombosis, stroke, infection, and GI bleeding. Using an additional VAD device to support right heart function means dual drive lines, two controllers, and additional power requirements, with nearly double the complication rate. Current survival for Bi-ventricular support solutions is comparable to TAH, and is currently at <60% at 12 months. With this prognosis, while the survival with a TAH far surpasses the terminal alternative of hospice care and palliative treatment, there is significant room for improvement for these sickest patients.
“The VAD technology has leapfrogged the total heart. … The risk profile is also different for patients that get a Total Artificial Heart compared to an LVAD, so it's not a fair comparison. The LVADs are simply a better surgery.” - Peter Eckman, MD
Predictions For Next-Gen MCS devices
For VADs to better fill the shortage of donor organs, they will need to further reduce complications, particularly drive-line infections, thrombosis, and 
short untethered times. The clinical trials for the Heartware and, particularly, the HeartMate3 LVADs are very promising for greater use of these devices as destination therapy with improved quality of life, fewer side effects and improved survivorship. Surgeons believe that the upcoming generation of LVADs currently in clinical trials have mostly addressed the problem of device thrombosis. Expected developments in the next few years include reduced implant size, improved signal transmission, improved electronics/controllers, and greater energy storage capacity for longer untethered time. The technical developments and improved patient management is expected to improve outcomes, particularly the current stroke rate (>10% at one year) [P. Eckman, MD], the most impactful remaining challenge to solve for the LVAD population.
"The [cardiac care] referring community does not care about pump thrombosis or minor GI bleeding; but, when their patient has a stroke, you don't see a lot of other patient [referrals] from them." -A. Boyle, MD
For the sickest patients that cannot match with a donor heart, developments in Total Artificial Hearts continues with evolution of the Syncardia Jarvik7 series and new upcoming devices like the Carmat, Reinhart, and Cleveland Clinic products.
Moving toward the “Ideal solution for patients to get 'implant-and-forget' devices like a pacemaker" [F. Arabía, MD], the greater progress may come from improvements in training of the healthcare provider team and medical economics when considering QALY metrics. Cardiologists, primary care physicians, and caregivers need to be trained to, first, more quickly refer patients to heart failure specialists. In an upcoming article in Journal of Heart Diagnostic and Transplantation, the outcomes based on INTERMACS Profiles can be better with increased center experience and understanding of physiology, patient selection, and "earlier intervention and referrals …before the patients are already half dead." [Arabía]
“Outcomes are better if we get people before they are a total mess. The less sick they are, the better the outcomes tend to be." [P. Eckman]
Second, the healthcare team for recipients of these devices will need to better understand management of patients with Mechanical Circulatory Support. Without pulsatile flow, what is a ‘healthy’ blood pressure? With high flow from an effective pump, is an otherwise low hematocrit acceptable? How does a nursing home or hospice provider qualify a patient with an implanted LVAD or TAH? For the economic assessment, the procedure and complication costs are currently so high that even if the device is provided free of charge, the costs do not meet the $100k/QALY often considered a threshold by medical economists. It is expected that with better success and greater numbers of LVAD implantations, both the expertise and economics will improve for those patients that can be treated with only left heart support. For the sickest INTERMACS profile 1, 2 and 3 patients, significantly greater investment is needed for the development of TAH technology to move beyond the aging Jarvik-style device. This investment will likely need to come from a government-level initiative, according to Dr. Arabia, since the economics of TAH today cannot justify the economic needs of for-profit business concerns and investors. Current technology developments for mechanical circulatory support provide hope for patients suffering from heart failure; however, healthcare system economics will need to catch up to the engineers and surgeons.
