Both BTT and DT small BSA patients had a marked improvement in NYHA Classification. Before implant, no patients reported NYHA Class I/II symptoms. At 6 months post implant, more than 75% of small BSA patients had improved to NYHA class I/II with sustained improvement through 12 months (Figure 3A, B).
This study represents the largest cohort of adult patients with a BSA < 1.5 m2 implanted with a CF-LVAD and support the use of CF-LVAD therapy in this patient population.
The post implant survival of small BSA patients are comparable with the published HMII post approval BTT and DT studies where the mean BSA was 2.03 ± 0.25 and 2.01 ± 0.29 m2, respectively.4,5 The post implant survival of the small BSA BTT cohort was 84% ± 4% and 81% ± 5% at 6 months and 1 year, respectively. Although not statistically significant, the small BSA DT cohort had improved 1 and 2 year post implant survival compared with the DT PAS (84% ± 6% vs. 74% ± 3% and 79% ± 8% vs. 61% ± 3%, respectively; p = 0.105).
The adverse event profile of the small BSA patients is equally as comparable with the post approval HMII BTT and DT studies (Tables 4 and 5). For the BTT population, the small BSA cohort had adverse event rates that were not statistically different from the HMII BTT PAS for all the major adverse events rates studied, with the exception that there was less bleeding noted in the small BSA cohort (0.91 vs. 1.44 eppy). Similarly, the adverse event profile for the DT population was not dissimilar from the post approval DT cohort, although more hemolysis was noted in the small BSA cohort (0.16 vs. 0.06 eppy). The reason for a higher incidence of hemolysis in the small BSA cohort is unclear. Increased hemolysis may be associated with the cannula position in a small BSA patient, smaller relative circulating blood volume passing through the rotor, or other factors all of which require further investigation. However it does not appear to be related to thrombus, which was similar at 0.03 to 0.04 eppy between cohorts, and stroke at 0.04 eppy was actually trending to be lower in the smaller patients but this did not reach statistical significance.
Paralleling comparable post implant survival outcomes and adverse event profiles of the small BSA patients is the marked improvement in NYHA functional class with the majority of patients reporting class I/II post implant, suggesting that the small BSA patients enjoy not only morbidity and mortality benefits but also improved quality of life with LVAD therapy.
The US clinical trial of the HM II also studied two small BSA patient (BSA < 1.5) cohorts, one for DT (n = 24) and one for BTT (n = 10), which were analyzed separately in the trial. The BTT cohort was composed of 10 females and was published in the device labeling.6 All small BSA patients survived to 180 days post implant with 86% improving from NYHA class IV to class I/II after 3 months. Six minute walk distance also increased an average of 230 m in the small BSA cohort versus 247 m in the primary study cohort. Adverse event rates were similar to those measured in the primary study cohort. Patients with small body size were comparable with larger patients in the clinical study; however, the number of small BSA patients was too few to make definitive conclusions.
A recent report by Cabrera et al.8 utilizing the INTERMACS registry compared outcomes of 28 pediatric patients aged 11 to 18 years compared with young adults aged 19 to 39 years implanted with the HMII. At 6 months, the composite of survival to transplantation, ongoing support, or recovery was 96% for the pediatric group, not dissimilar to the young adult group (p = 0.330). The median BSA for the pediatric group was 1.91 m2 (1.47–2.65).
Interestingly, the results of the Japanese HMII prospective BTT trial were recently published.9 The six patients enrolled in this study had a mean BSA of 1.58 ± 0.17 m2. All patients were inotrope dependent and failing medical management at baseline. Although a small trial, at 6 months post implant, there were no deaths and all patients were alive with ongoing support. Functional status assessed by the 6 minute walk distance increased from 268 ± 92 m at baseline to 399 ± 105 m, and 100% of the patients were reported to be NYHA class I/II in follow-up. All the six patients eventually were successfully transplanted.
Unlike previous studies, but similar to the small patient cohort in the US clinical trial, this report is unique in that the study population is predominantly female. The majority of clinical trials and investigations in heart failure have traditionally been comprised of predominantly male populations. In the mechanical circulatory support literature, the female sex is particularly underrepresented. This is especially true historically with the use of the first-generation pulsatile displacement pumps, where smaller anatomies were physically unable to accommodate the larger devices. A recent single center study looked at sex-specific outcomes in the CF-LVADs era.10 Their study population included 130 patients, 35 (27%) of whom were female. The investigators found comparable short and mid-term post implant survival outcomes, hospital length of stay, readmissions rates, and post operative complications between males and females.
Boyle et al.11 retrospectively analyzed the pre operative risks for bleeding and stroke during CV-LVAD support in the HMII BTT and DT clinical trials. Of 956 patients, 220 (23%) were female. The authors found an increased incidence of thrombotic and hemorrhagic events in female patients compared with male patients. In this report, 83% of the study population was female, and with comparable post implant survival outcomes and adverse event rates matching the post approval LVAD studies, it may be suggested that females benefit as much from CF-LVAD therapy as their male counterparts.
This study has several important limitations. The PASs included the small BSA cohort but because the majority of patients in the PAS had a BSA > 1.5 m2, the impact of this inclusion would not be clinically significant. The BTT and DT PAS cohorts were not implanted during the same time-frame which may have influenced outcomes as management strategies are expected to improve with time and experience. The INTERMACS database was designed as a registry and not for the purpose of analyzing outcomes in small BSA patients implanted with CF-LVADs. Furthermore, the survival outcomes and adverse event rates of the small BSA patients compared with the post approval BTT and DT studies were not risk adjusted.
In conclusion, this study represents the largest cohort of adult patients analyzed with a small BSA < 1.5 m2 receiving a CF-LVAD. The majority of the patient population was female. With comparable post implant survival outcomes and adverse event rates comparable with the published post approval BTT and DT studies, this study supports the use of CF-LVADs as BTT or DT in patients with a small BSA < 1.5 m2.
1. Kirklin JK, Naftel DC, Pagani FD, et al. Seventh INTERMACS annual report: 15,000 patients and counting. J Heart Lung Transplant 2015.34: 1495–1504.
2. Lund LH, Edwards LB, Kucheryavaya AY, et al; International Society for Heart and Lung Transplantation: The Registry of the International Society for Heart and Lung Transplantation: Thirtieth Official Adult Heart Transplant Report–2013; focus theme: age. J Heart Lung Transplant 2013.32: 951–964.
3. Kirklin JK, Naftel DC, Pagani FD, et al: Sixth INTERMACS annual report: A 10,000-patient database. J Heart Lung Transplant 2014.33: 555–564.
4. Starling RC, Naka Y, Boyle AJ, et al: Results of the post-U.S. Food and Drug Administration-approval study with a continuous flow left ventricular assist device as a bridge to heart transplantation: A prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol 2011.57: 1890–1898.
5. Jorde UP, Kushwaha SS, Tatooles AJ, et al; HeartMate II Clinical Investigators: Results of the destination therapy post-food and drug administration approval study with a continuous flow left ventricular assist device: A prospective study using the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol 2014.63: 1751–1757.
6. HeartMate II Left Ventricular Assist System Instructions for Use. 2014, Pleasanton, CA: Thoratec Corporation.106020.G.
7. 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: 141–156.
8. Cabrera AG, Sundareswaran KS, Samayoa AX, et al: Outcomes of pediatric patients supported by the HeartMate II left ventricular assist device in the United States. J Heart Lung Transplant 2013.32: 1107–1113.
9. Kyo S, Ono M, Sawa Y, et al; HeartMate II Japanese Clinical Investigators: Results of the prospective multicenter Japanese bridge to transplant study with a continuous-flow left ventricular assist device. J Artif Organs 2014.17: 142–148.
10. Tsiouris A, Morgan JA, Nemeh HW, Hodari A, Brewer RJ, Paone G: Sex-specific outcomes in patients receiving continuous-flow left ventricular devices as a bridge to transplantation or destination therapy. ASAIO J 2014.60: 199–206.
11. Boyle AJ, Jorde UP, Sun B, et al; HeartMate II Clinical Investigators: Pre-operative risk factors of bleeding and stroke during left ventricular assist device support: An analysis of more than 900 HeartMate II outpatients. J Am Coll Cardiol 2014.63: 880–888.
Keywords:Copyright © 2016 by the American Society for Artificial Internal Organs
LVAD; BSA; BMI; INTERMACS; HeartMate II