Faculty Bibliography

BACKGROUND: Although continuous-flow left ventricular assist devices (LVAD) are durable and reliable, device replacement will be inevitable in some patients. We evaluated the incidence and outcomes of pump replacement procedures with the HeartMate II (Thoratec Corporation, Pleasanton, CA) LVAD. METHODS: Data were obtained from 1,128 patients implanted from March 2005 to January 2010 with the HeartMate II during the clinical trials for bridge to transplant and destination therapy. The operative mortality associated with the replacement procedure was determined. RESULTS: The mean duration of HeartMate II support was 568 +/- 535 days (cumulative duration: 1,755 patient-years, longest: 6.5 years). A total of 72 (6.4%) patients underwent 79 LVAD replacements (0.045 events/patient-year) of which 2 were in the initial operation and 77 in separate procedures. Reasons for replacement were percutaneous lead damage (36 events, 3.0%), device thrombosis (25 events, 2.1%), infection (7 events, 0.6%), and miscellaneous other (11 events, 0.9%). The median time to pump replacement was 428 days (range 0 to 1,474). Of the 77 replacement procedures, there were 5 (6.5%) operative deaths within 30 days. The causes of death were device thrombosis, right heart failure, multisystem organ failure, and bleeding. One year after exchange (median 2.1 years after initial implant), 30% had died, 5% were transplanted, and 65% were ongoing and alive. CONCLUSIONS: HeartMate II device failure requiring pump replacement is infrequent, but when required can be done safely. These data continue to provide encouraging evidence supporting HeartMate II use for long-term circulatory support.

The recent success of continuous-flow circulatory support devices has led to the growing acceptance of these devices as a viable therapeutic option for end-stage heart failure patients who are not responsive to current pharmacologic and electrophysiologic therapies. This article defines and clarifies the major classification of these pumps as axial or centrifugal continuous-flow devices by discussing the difference in their inherent mechanics and describing how these features translate clinically to pump selection and patient management issues. Axial vs centrifugal pump and bearing design, theory of operation, hydrodynamic performance, and current vs flow relationships are discussed. A review of axial vs centrifugal physiology, pre-load and after-load sensitivity, flow pulsatility, and issues related to automatic physiologic control and suction prevention algorithms is offered. Reliability and biocompatibility of the two types of pumps are reviewed from the perspectives of mechanical wear, implant life, hemolysis, and pump deposition. Finally, a glimpse into the future of continuous-flow technologies is presented.

Heart transplantation remains the gold standard for long-term cardiac replacement, but a shortage of donor organs will always limit this option. For both transplant-eligible and noneligible patients, advances in mechanical circulatory support have revolutionized the options for the management of end-stage heart failure, and this technology continues to bring us closer to a true alternative to heart transplantation. This review provides a perspective on the past, present and future of mechanical circulatory support and addresses the changes in technology, patient selection and management strategies needed to have this therapy fully embraced by the heart failure community, and perhaps replace heart transplantation either as the therapy of choice or as a strategy by which to delay transplantation in younger patients.

The development of ventricular assist devices (VADs) over the past 5 decades as therapy for advanced heart failure (HF) has been extraordinary. Since the original VAD design by Michael DeBakey in the early 1960s, numerous devices for mechanical circulatory support have been engineered, assessed in preclinical studies, applied to human patients in large multicenter clinical trials, and now, select devices are Food and Drug Administration-approved therapy for advanced HF patients. This review highlights select examples of durable VADs from the engineering aspect of design and conception to experimental studies and clinical application underscoring the remarkable progression of such technology to now becoming the standard of care for many advanced HF patients.

BACKGROUND: Several arrhythmogenic mechanisms have been inferred from animal heart failure models. However, the translation of these hypotheses is difficult because of the lack of functional human data. We aimed to investigate the electrophysiological substrate for arrhythmia in human end-stage nonischemic cardiomyopathy. METHODS AND RESULTS: We optically mapped the coronary-perfused left ventricular wedge preparations from human hearts with end-stage nonischemic cardiomyopathy (heart failure, n=10) and nonfailing hearts (NF, n=10). Molecular remodeling was studied with immunostaining, Western blotting, and histological analyses. Heart failure produced heterogeneous prolongation of action potential duration resulting in the decrease of transmural action potential duration dispersion (64 +/- 12 ms versus 129 +/- 15 ms in NF, P<0.005). In the failing hearts, transmural activation was significantly slowed from the endocardium (39 +/- 3 cm/s versus 49 +/- 2 cm/s in NF, P=0.008) to the epicardium (28 +/- 3 cm/s versus 40 +/- 2 cm/s in NF, P=0.008). Conduction slowing was likely due to connexin 43 (Cx43) downregulation, decreased colocalization of Cx43 with N-cadherin (40 +/- 2% versus 52 +/- 5% in NF, P=0.02), and an altered distribution of phosphorylated Cx43 isoforms by the upregulation of the dephosphorylated Cx43 in both the subendocardium and subepicardium layers. Failing hearts further demonstrated spatially discordant conduction velocity alternans which resulted in nonuniform propagation discontinuities and wave breaks conditioned by strands of increased interstitial fibrosis (fibrous tissue content in heart failure 16.4 +/- 7.7 versus 9.9 +/- 1.4% in NF, P=0.02). CONCLUSIONS: Conduction disorder resulting from the anisotropic downregulation of Cx43 expression, the reduction of Cx43 phosphorylation, and increased fibrosis is likely to be a critical component of arrhythmogenic substrate in patients with nonischemic cardiomyopathy.