Multicenter clinical evaluation of the HeartMate vented electric left ventricular assist system in patients awaiting heart transplantation

AbstractBackground: Despite advances in heart transplantation and mechanical circulatory support, mortality among transplant candidates remains high. Better ways are needed to ensure the survival of transplant candidates both inside and outside the hospital. Methods: In a prospective, multicenter clinical trial conducted at 24 centers in the United States, 280 transplant candidates (232 men, 48 women; median age, 55 years; range, 11-72 years) unresponsive to inotropic drugs, intra-aortic balloon counterpulsation, or both, were treated with the HeartMate Vented Electric Left Ventricular Assist System (VE LVAS). A cohort of 48 patients (40 men, 8 women; median age, 50 years; range, 21-67 years) not supported with an LVAS served as a historical control group. Outcomes were measured in terms of laboratory data (hemodynamic, hematologic, and biochemical), adverse events, New York Heart Association functional class, and survival. Results: The VE LVAS–treated and non–VE LVAS–treated (control) groups were similar in terms of age, sex, and distribution of patients by diagnosis (ischemic cardiomyopathy, idiopathic cardiomyopathy, and subacute myocardial infarction). VE LVAS support lasted an average of 112 days (range, < 1-691 days), with 54 patients supported for > 180 days. Mean VE LVAS flow (expressed as pump index) throughout support was 2.8 L · min–1 · m–2. Median total bilirubin values decreased from 1.2 mg/dL at baseline to 0.7 mg/dL (P =.0001); median creatinine values decreased from 1.5 mg/dL at baseline to 1.1 mg/dL (P =.0001). VE LVAS–related adverse events included bleeding in 31 patients (11%), infection in 113 (40%), neurologic dysfunction in 14 (5%), and thromboembolic events in 17 (6%). A total of 160 (58%) patients were enrolled in a hospital release program. Twenty-nine percent of the VE LVAS-treated patients (82/280) died before receiving a transplant, compared with 67% of controls (32/48) (P <.001). Conversely, 71% of the VE LVAS–treated patients (198/280) survived: 67% (188/280) ultimately received a heart transplant, and 4% (10/280) had the device removed electively. One-year post-transplant survival of VE LVAS–treated patients was significantly better than that of controls (84% [158/188] vs 63% [10/16]; log rank analysis P =.0197). Conclusion: The HeartMate VE LVAS provides adequate hemodynamic support, has an acceptably low incidence of adverse effects, and improves survival in heart transplant candidates both inside and outside the hospital. The studies of the HeartMate LVAS (both pneumatic and electric) for Food and Drug Administration approval are the only studies with a valid control group to show a survival benefit for cardiac transplantation

Preclinical evaluation

Mechanical circulatory and respiratory support systems are classified as high-risk devices that support or sustain human life by regulatory authorities worldwide and as such are required to undergo rigorous preclinical evaluation prior to adaption as treatment methods. This chapter discusses preclinical evaluation methods used to guide cardiac and respiratory assist device development, with different evaluation strategies (i.e., in silico, in vitro, and in vivo) described in depth. During in silico device evaluation, utilizing numerical simulations, potential devices and their interaction with a simulated cardiovascular system can be tested without having to build actual device prototypes or test set-ups. Actual device prototypes are then evaluated in vitro (e.g., in mock circulation loops, blood loops, or particle image velocimetry systems), which is necessary to comply with FDA regulations prior to in vivo trials. Following in silico and in vitro testing, devices are assessed in vivo utilizing large animal models, which are a critical component in the effort to translate device development into beneficial clinical practice. Only after successful preclinical evaluation can new devices undergo clinical trials and commercial distribution

Properties of blood-contacting surfaces of clinically implanted cardiac assist devices: gene expression, matrix composition, and ultrastructural characterization of cellular linings

The development of implantable cardiac assist devices for prolonged circulatory support has been impeded by the problem of excessive thrombogenesis on the blood-prosthetic interface, with subsequent embolization. To overcome this obstacle, a ventricular assist device has been developed with textured blood-contacting surfaces to encourage the formation of a tightly adherent, hemocompatible, biological lining. In this study, we applied molecular biological techniques, in conjunction with conventional ultrastructural and biochemical techniques, to characterize the biological linings associated with the blood-contacting surfaces of 11 of these devices, which had been clinically implanted for durations ranging from 21 to 324 days. No clinical thromboembolic events or pump-related thromboembolism occurred. Biological linings developed on the textured surfaces composed of patches of cellular tissue intermingled with areas of compact fibrinous material. In addition, islands of collagenous tissue containing fibroblast-like cells appeared after 30 days of implantation. Many of these cells contained microfilaments with dense bodies indicative of myofibroblasts. RNA hybridization analyses demonstrated that the colonizing cells actively expressed genes encoding proteins for cell proliferation (histones), adhesion (fibronectin), cytoskeleton (actin, vimentin) and extracellular matrix (types I and III collagen). Linings, which never exceeded 150 microns in thickness, remained free of pathological calcification. Textured blood-contacting surfaces induced the formation of a thin, tightly adherent, viable lining which exhibited excellent long-term hemocompatibility