Author + information
- Eileen M. Hsich, MD∗ ()
- Heart and Vascular Institute at the Cleveland Clinic, Cleveland, Ohio
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University School of Medicine, Cleveland, Ohio
- ↵∗Reprint requests and correspondence:
Dr. Eileen M. Hsich, Heart and Vascular Institute, Cleveland Clinic, J3-4, 9500 Euclid Avenue, Cleveland, Ohio 44195.
“Yeah my mama she told me, ‘don't worry about your size’”
—Meghan Trainor, All About That Bass (1)
For many years, adult patients with a body surface area (BSA) <1.5 m2 had few options to bridge to transplantation and no option for destination therapy. The evolution of ventricular assist devices has improved our ability to rescue heart failure patients and has allowed us to consider the possibility that size does not matter.
The conception of mechanical circulatory devices began more than 50 years ago. In 1964, the Artificial Heart Program was organized by the National Heart Institute, and funding was provided to support the endeavor (2). By 1967, DeBakey (3) had successfully bridged to recovery a “thin and critically ill” 37-year-old woman and a 16-year-old girl after valvular surgery with a temporary extracorporeal pneumatic device that had the inflow cannula in the left atrium and the outflow cannula in the right axillary artery. The young woman needed mechanical circulatory support for 10 days, and the teenage girl for 4 days (3). By 1978, the first patient was bridged to heart transplantation with a temporary left ventricular assist device for 5 days, but died a few weeks later from a perforated bowel (4). By the 1980s, long-term implantable electrical left ventricular assist devices were finally available, and the experience of 20 patients (BSA range 1.67 to 2.19 m2) who were mechanically supported for 1 h to 90 days was reported, with 50% bridged to transplantation (5). This accomplishment led to the first generation of left ventricular assist devices.
The first generation of devices was pulsatile, with positive displacement pumps. These devices ranged in weight from 2.2 lbs (Novacor, World Heart Corporation, Ottawa, Ontario, Canada) to 2.5 lbs (HeartMate XVE, Thoratec, Pleasanton, California) and required the recipient to have a BSA >1.5 m2 (Figure 1). The subsequent generations of devices were continuous-flow pumps that were much lighter (i.e., <1 lb) with axial or centrifugal flow (6). Most of the continuous-flow devices fit in “small” people, yet their safety remains unclear.
The excellent study by Zafar et al. (7) in this issue of JACC: Heart Failure provides the first substantial evidence that continuous-flow devices are relatively safe and provide similar survival benefit for patients with BSA ≤1.5 m2 compared with BSA >1.5 m2. Their study included all adults in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) from April 2008 to September 2013 with a continuous-flow device and excluded those patients with biventricular assist device support. Patients with BSA ≤1.5 m2 were mostly women (68% vs. 20%; p < 0.001), were more likely Hispanic (10.4% vs. 6.1%; p = 0.025), had lower serum creatinine (1.2 mg/dl vs. 1.4 mg/dl; p < 0.001) and higher BNP (1,703 pg/ml vs. 1,151 pg/ml, p < 0.001) compared with patients with BSA >1.5 m2. There were few adverse events with continuous-flow devices, but patients with BSA ≤1.5 m2 had a higher risk of driveline infection and nonmediastinal bleeding. They also had a relatively lower risk of renal insufficiency or right ventricular failure compared with patients with BSA >1.5 m2.
This study by Zafar et al. (7) is the largest ventricular assist device cohort of adult patients with BSA ≤1.5 m2. The BSA ≤1.5 m2 cohort had 231 patients and 57 deaths, which was relatively small compared with 10,582 patients and 2,672 deaths with BSA >1.5 m2. Their results are similar to the J-MACS (Japanese Registry for Mechanical Assisted Circulatory Support) that compared 30 HeartMate II patients with BSA <1.5 m2 to 74 HeartMate II patients with BSA ≥1.5 m2 and found no difference in survival, but a higher driveline infection rate among patients with BSA <1.5 m2 (8). Should we be surprised? Not really. In both studies, patients with BSA <1.5 m2 were mostly women, and prior studies with INTERMACS data revealed no sex difference in survival with continuous-flow devices (9). The higher rate of infection among “smaller” adults remains unclear, but as Zafar et al. (7) stated, it may be related to nutritional status and cardiac cachexia. Their study showed no difference in baseline albumin and pre-albumin serum levels, but we do not know the degree of missingness and/or the method of imputation. They also noted a higher risk of bleeding in patients with BSA ≤1.5 m2 driven predominately by the male population. The mechanism remains unclear and will need to be confirmed with larger studies.
What more do we need to know about size? We do not have adequate data for adult patients with BSA <1.3 m2. The median BSA in the study by Zafar et al. (7) was 1.42 m2 (interquartile range: 1.34 to 1.46 m2). Even the Japanese registry with BSA <1.5 m2 (n = 30) had a mean BSA 1.41 ± 0.64 m2.
Can we glean anything from pediatric patients with mechanical circulatory support? In 1 INTERMACS study comparing HeartMate II children age 11 to 18 years to young adults age 19 to 39 years, there was no significant difference in 6-month survival, but children had a higher rate of reoperation for bleeding. This study was limited by size (n = 28 children, n = 359 adults) and BSA (pediatric median BSA: 1.91 m2, range 1.47 to 2.65 m2 vs. adult median BSA: 2.08 m2, range 1.12 to 3.10 m2) (10). In a larger analysis using the Pediatric Heart Transplant Study database, 99 children underwent ventricular assist device implantation as a bridge to transplantation between 1993 to 2003. The cohort ranged in age from 2 days to 17.9 years and had a median BSA of 1.5 m2 (range 0.2 to 2.7 m2). In this registry, 6- and 12-month survival to transplantation were 76% and 71%, respectively. Female sex, congenital heart disease, and era between 1993 and 1999 were significant mortality risk factors (11). Finally, in the most recent analysis limited to continuous-flow devices between September 2012 and June 2015 using the PediMACS (Pediatric Interagency Registry for Mechanical Circulatory Support) database, there was no significant difference in 6- and 12-month survival between 109 children and 3,894 adults in INTERMACS implanted with a continuous-flow device as bridge to transplant (6-month survival: 88% PediMACS vs. 89% INTERMACS; 12-month survival: 88% PediMACS vs. 84% INTERMACS). The median BSA in PediMACS was 1.7 m2 (range 0.7 to 2.7 m2) compared with 2.1 m2 (range 0.6 to 3.7 m2) in the adult INTERMACS cohort (12). Although all of these pediatric studies included patients with BSA <1.3 m2, their median BSA was ≥1.5 m2. Therefore, we still do not have sufficient data to answer the safety and efficacy for this “smaller” subgroup. This population will likely benefit in the future from pediatric devices that are either approved or under investigation by the U.S. Food and Drug Administration (13–15).
Meaningful studies like that of Zafar et al. (7) are only possible with the development of national registries to follow patients that are underserved and who do not have safety/survival data available. The INTERMACS database is the collaborative effort of clinicians, scientists, industry, the National Heart, Lung, and Blood Institute, the Centers for Medicare and Medicaid Services, and the U.S. Food and Drug Administration. Since the inception of the database in 2006, over 19,500 patients have been enrolled in the registry, including those with left ventricular assist devices, right ventricular assist devices, and total artificial hearts (16). Despite the large size of the registry, more data is needed to determine the safety and effectiveness of mechanical circulatory support in patients with very low BSA. Smaller devices will soon be available, and in the near future we likely will say “Yeah my mama she told me, don't worry about your size” (1).
↵∗ Editorials published in JACC: Heart Failure reflect the views of the authors and do not necessarily represent the views of JACC: Heart Failure or the American College of Cardiology.
Dr. Hsich is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R56HL125420-01A1.
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- ↵The Five VAD Functional Generations. Available at: http://reliantheart.com/new-heart-assist-5/smallest-size-and-weight/. Accessed October 5, 2016.