Novel approaches in long term mechanical circulatory support

Abstract

Long term mechanical circulatory support using left ventricular assist devices (LVADs) remains an essential tool in managing patients with advanced heart failure, and in some patients can facilitate reverse remodelling of ventricular function. However, large groups of patients remain poorly served by current technologies, and understanding of reverse remodelling, including how to assess it in vivo, remains poor. I evaluate new approaches in long term mechanical support. Specifically, I assess: (1) the CircuLite Synergy LVAD and Sunshine Heart C-Pulse counterpulsation device as novel methods for partial LV support, considering particularly their ability to facilitate reverse remodelling and propensity to induce coagulopathy; (2) gene therapy with the AAV1.SERCA2a product as a novel adjunctive therapy, considering particularly its safety and feasibility in LVAD patients in the SERCA-LVAD trial; and (3) novel biomarkers for use in LVAD patients, with focus on strain echocardiography and circulating microRNA. I report that (1) partial LV support is plausible as a concept and is beneficial in some patients, but there was no consistent evidence of ventricular reverse remodelling and, at the present time, high complication rates and difficulties with patient selection preclude its widespread adoption; (2) there were high rates of pump thrombosis in the Synergy LVAD, though there is no evidence of a device-specific coagulopathy to explain it; (3) gene therapy with AAV1.SERCA2a is safe and feasible in LVAD patients, though there was no evidence of significant efficacy benefit, in line with other clinical trials of this gene therapy in heart failure; (4) assessment of global circumferential strain is feasible in LVAD patients, but inconsistent image quality and effect of loading conditions limit its use; and (5) assessment of circulating microRNA profiles is feasible in LVAD patients, and preliminary data shows roles for specific miRs in patient selection and monitoring of LV function.Open Acces