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MedaMACS: The Medical Arm of Mechanically Assisted Circulatory Support


links image GARRICK C STEWART, MD
gcstewart@partners.org


After half a century of clinical development, mechanical circulatory support (MCS) devices are now in widespread use for the treatment of advanced heart failure. With the completion of the first five-year phase of INTERMACS, the boundaries of device therapy have been defined and extended, with improved long-term outcomes allowing interest to shift toward placement of MCS devices into "less sick" advanced heart failure patients. Integral to the original intent of INTERMACS was a comparison to ambulatory patients living with advanced heart failure who are not currently receiving MCS. Until now, the lack of information on outcomes with continued medical therapy has limited the ability to advance indications for MCS into the "less sick".

Although the progressively better outcomes with continuous flow left ventricular assist devices (LVADs) documented in INTERMACS might be anticipated to attract ambulatory patients not yet dependent on inotropes, such patients currently comprise fewer than 20% of device recipients [1]. As mechanical support moves into the less sick patient profiles, decision making will be increasingly influenced by factors beyond survival alone. There is an urgent need for functional and quality of life data in patients limited with advanced heart failure both before the decision to proceed with MCS, and after therapy [2]. MedaMACS, the Medical Arm of Mechanically Assisted Circulatory Support, will address these needs.

On January 17-18, 2013 clinicians from 12 VAD/Transplant centers across the United States gathered in Washington, DC for the inaugural MedaMACS investigators meeting. MedaMACS will map the terrain of contemporary medical therapy for advanced heart failure, identify ambulatory patients for current MCS devices, define a broader context for the next generation of MCS trials and future devices, and design integrated endpoints that move beyond survival alone. MedaMACS will enroll systolic heart failure patients with INTERMACS Profiles 4-7 and at least one heart failure hospitalization in the prior year, who are neither inotrope-dependent nor listed for cardiac transplantation. MedaMACS will characterize those patients who are not currently receiving MCS for various reasons, including relative contra-indications, their own preferences, or their characterization as "less sick" either by perception or objective criteria.

MedaMACS is set to launch in March 2013 and will be housed with INTERMACS at the University of Alabama Birmingham. The protocol has been developed with guidance from the National Heart Lung and Blood Institute. Target enrollment will be 300 patients at 12 certified destination therapy VAD centers in the United States, followed by comprehensive two-year clinical follow-up with timed endpoints of death, transplant or MCS placement. Two separate baseline face-to-face assessments one month apart will define the early trajectory of illness. Adverse events on medical therapy, such as recurrent hospitalization or stroke, will be determined and compared to those experienced after VAD. Of equal weight will be longitudinal determination of functional capacity, health related quality of life, frailty, and satisfaction with therapy. For many ambulatory patients with chronic heart failure, the magnitude and predictability of expected improvement in functional status with a VAD will likely influence their decision to proceed with MCS more than the margin of survival benefit [3].

The feasibility of the MedaMACS approach has already been validated in a successful screening pilot study, which enrolled 168 patients at 10 JCAHO-certified MCS programs across the United States in 2010-11 using similar entry criteria. The MedaMACS screening pilot collected baseline data from usual care practices and had limited telephone follow-up through 12 months. These preliminary screening pilot data produced several intriguing findings that have informed the discussion about MCS deployment in less sick INTERMACS profiles, while providing a taste of what will become available from MedaMACS.

Highlights from the MedaMACS screening pilot were reviewed at the investigators meeting in January. Screening pilot participants had an average age of 57 years, a mean EF of 18%, and a median of 2 HF hospitalizations in the previous 6 months. In all, 91% would be at low or intermediate risk for LVAD implant according to the HeartMate II risk score [4]. Although a subgroup chronic heart failure patients may have low estimated perioperative risk for LVAD implant, some may rightfully ask: who would want an LVAD for ambulatory heart failure? After presenting the risks and benefits of MCS therapy, 56% of patients surveyed said they would definitely or probably want LVAD therapy [5]. Enthusiasm for LVAD increased in patients with sicker INTERMACS profiles, as assigned by their treating physician, further validating these profiles as a marker of disease burden.

Jeffrey Teuteberg (University of Pittsburgh) presented preliminary outcomes from the MedaMACS screening pilot. A surprising one in three participants either died or underwent VAD/transplant within 6 months of enrollment [6]. Screening pilot participants carried a significant burden of disease, as evidenced both by the high event rate with a medical therapy strategy and their willingness to consider invasive surgical therapy. Quality of life was also markedly reduced in MedaMACS participants when measured by the EuroQOL instrument. Though the degree of anxiety and depression along with pain and suffering in the MedaMACS cohort was equivalent to INTERMACS subjects before VAD implant, patients selected for MCS were more limited in mobility and self-care [7].

There appears to be a clear and present opportunity to improve the lives of patients with moderately advanced heart failure using current MCS devices, though more work is needed to refine patient selection. Michelle Kittleson (Cedars-Sinai Heart Center) outlined that 49% of MedaMACS participants had been previously evaluated for transplant and/or VAD therapy [8]. The decision to proceed with evaluation for advanced therapies was not consistently delineated by standard clinical features. These screening pilot data highlight the urgent need for better characterization and triage of heart failure patients to find those most likely to benefit from MCS therapy. The latest results from the MedaMACS screening pilot will be presented at the International Society of Heart and Lung Transplant Annual Meeting and Scientific Sessions in Montreal in April 2013.

In the years to come, MedaMACS will provide important context for the next wave of device studies in moderately advanced heart failure. The NIH has sponsored the Randomized Evaluation of VAD Intervention before Intrope Therapy (REVIVE-IT) trial to study NYHA class III patients ineligible for transplant [9]. In addition, the industry sponsored ROADMAP trial will be a prospective, non-randomized observational study of ambulatory patients with NYHA III/IV symptoms not dependent on inotropes [10]. Together with REVIVE-IT and ROADMAP, the MedaMACS program will help refine selection for MCS from the ambulatory heart failure population within which the greatest benefit of mechanical support is anticipated. MedaMACS will also fulfill the urgent need for parallel functioning and quality of life data in advanced heart failure patients both before the decision to proceed with MCS and after therapy. The synergy between INTERMACS and MedaMACS will support the new era of shared decision-making in heart failure that will be pivotal in moving toward the 21st century goal of patient-centered care [11].



Disclosure Statement: The author reports no relevant financial relationships to disclose.


Dr. Stewart is an Associate Physician at Brigham and Women's Hospital and an Instructor at Harvard Medical School, Boston, Massachusetts, USA.


References:

  1. Kirklin JK, Naftel DC, Kormos RL, et al. Fifth INTERMACS annual report: Risk factor analysis from more than 6,000 mechanical circulatory support patients. J Heart Lung Transplant 2013;32:141-56.
  2. Grady KL, Warner Stevenson L, Pagani FD, et al. Beyond survival: Recommendations from INTERMACS for assessing function and quality of life with mechanical circulatory support. J Heart Lung Transplant 2012;31:1158-64.
  3. Stewart GC, Brooks P, Pratibhu PP, et al. Thresholds of physical activity and life expectancy for patients considering destination ventricular assist devices. J Heart Lung Transplant 2009;28:863-9.
  4. Cowger J, Kittleson M, Patel C, et al. End stage heart failure: Are we missing patients who may benefit from left ventricular assist device support? Circulation 2011;124:A8490.
  5. Stewart GC, Kittleson MM, Cowger JA, et al. Who wants an LVAD for ambulatory heart failure? J Card Failure 2011;17:S37-S38.
  6. Teuteberg JJ, Kittleson M, Cowger J, et al. Prediction of events in patients with advanced heart failure: Application of the Seattle heart failure model to the MedaMACS population. J Heart Lung Transplant 2012;31:S63.
  7. Patel P, Stewart GC, Kittleson MM, et al. Patients with INTERMACS 4-7 heart failure have a reduced quality of life. J Heart Lung Transplant 2012;31:S62-S63.
  8. Kittleson M, Stewart GC, Cowger JA, et al. Need for triage in advanced heart failure. Circulation 2012;126:A14709.
  9. Baldwin JT, Mann DL. NHLBI's program for VAD therapy for moderately advanced heart failure: the REVIVE-IT pilot trial. J Card Failure 2010;16:855-8.
  10. www.clinicaltrials.gov; NCT01452802 (Accessed February 2013)
  11. Allen LA, Stevenson LW, Grady KL, et al. Decision making in advanced heart failure: A scientific statement from the American Heart Association. Circulation 2012;125:1928-52.