Mechanical circulatory support (MCS) is an established treatment modality for end stage heart failure. Let’s take a gander at some of the classic papers that advanced the field, starting with the REMATCH trial.
The Infographic Review of the REMATCH Trial
Let’s Deep Dive This Thing
Introduction
End stage heart failure exerts a heavy price on those who suffer it: high mortality and low quality of life. The profound shortage of donor hearts makes universal transplantation unrealistic as a mainstay treatment. In 2001 when the REMATCH study was published, only 3000 or so adult heart transplants were performed2 (the number has improved over the next two decades to ~4000 annually, but far away from meeting the need). Thus, the idea of “durable cardiac support” in those who were not candidates for organ donation emerged. The FDA approved the first LVAD for bridge to transplant in 1994. The REMATCH trial studied an early generation LVAD and optimal medical therapy vs optimal medical therapy alone in this population in a transplant ineligible population (“destination” therapy).
What did they do?
Rose and colleagues conducted a multi-center, open label block randomized controlled trial. The study was investigator initiated and supported by the NHLBI, but also received funding from Thoratec. Adult patients were considered for inclusion if they had NYHA Stage IV heart failure for over 90 days, had a low peak oxygen consumption (<12 ml/kg/min) or have been unable to be weaned from intravenous inotropes. They also had to be medically optimized, defined as being on a regimen of digoxin, diuretics, and an ACEi for at least 90 days prior to randomization. Ejection fraction had to be equal to or less than 25% in the context of optimal medical management. Exclusions of note were technical obstacles in judgement of the surgeon, BMI >40, pregnancy or pulmonary hypertension.
Patients randomized to the device received the Thoratec Heartmate VE LVAD and optimal medical management. The control group was optimal medical management as aforementioned. A pilot study3 was performed to allow reliability assessment of the device and to further the experience of the implanting surgeons with the device.
Primary outcome was the effect of the LVAD on mortality from all causes. Secondary outcomes of note were quality of life assessments and adverse events.
What did they find?
129 Patients were recruited. The groups were well matched at baseline. The LVAD group had a reduction of 48% in the risk of death from any cause (RR 0.52, CI 0.34 – 0.78, P = 0.001) as compared to the medical therapy group.
One year survival for the LVAD group was 52% vs 25% for the medical group, which was statistically significant (P = 0.002, NNT = 3.7). The trend of improved survival persisted to two years, although lost statistical significance. Median survival was 408 days in the device group and 150 for medical management. The mortality benefit was greater in younger patients (<60 years old). Terminal heart failure was the most common cause of death in the medical group, whereas the most common causes of death in the device group were sepsis (41%) and device failure (17%).
Quality of life (QOL) was a mixed bag. Some tests of QOL were improved in the device group, namely the physical function and emotional role components of the SF-36. NYHA heart failure class was significantly reduced at 1 year, with the device group predominantly NYHA II while medical management remained NYHA IV.
The device group was twice as likely to have a serious adverse event (rate ratio 2.35, CI 1.86-2.95), reported as adverse event rates per patient year. The most common defined serious adverse event was bleeding (42%), though device related sepsis (28%) was second. There were no device failures in the first year, but the probability of device failure at 2 years was 35%.
What should we take away from this?
This was the first study to demonstrate that LVADs are an option for destination therapy! However, adverse events such as bleeding, infection, and device failure would spur the development of improved device design over the next decade. It is important to read this paper in the context of the first generation HeartMate LVAD, and additional classic articles in this series address the improvements. Device failure incidence is much lower now.
References
- Rose, Eric A., et al. “Long-term use of a left ventricular assist device for end-stage heart failure.” New England Journal of Medicine 345.20 (2001): 1435-1443.
- Hosenpud, Jeffrey D., et al. “The Registry of the International Society for Heart and Lung Transplantation: eighteenth official report—2001.” The Journal of heart and lung transplantation 20.8 (2001): 805-815.
- Rose, Eric A., et al. “The REMATCH trial: rationale, design, and end points.” The Annals of thoracic surgery 67.3 (1999): 723-730.
