Long-term mechanical circulatory support: could it really have a public health impact?

Cardiovascular disease is a leading cause of death in North America and Europe, and heart failure represents a major component, affecting about 2.5% of the adult population [1, 2]. Ten percent of the heart-failure population experiences truly advanced heart failure, with limited long-term survival. For patients with New York Heart Association (NYHA) Class IV heartfailure symptoms poorly responsive to medical therapy, cardiac transplantation has dramatically improved the survival and quality of life, with a 2-year survival of 80% or more, and a median survival of >10 years [3]. Although cardiac transplantation represents the standard of care for eligible NYHA Class IV heart-failure patients, the limited availability of suitable donor hearts has restricted its application to about 2500 patients annually in North America and <1500 in Europe [3]. In Europe, in particular, despite the ongoing epidemic of heart failure, heart transplant activity has decreased since 2000 [3]. Thus, from a public-health perspective, cardiac transplantation exerts a minor impact on refractory Stage D heart failure. Durable mechanical circulatory support (MCS), originally introduced clinically as bridge-to-transplant (BTT) therapy, gained acceptance as long-term ‘destination therapy’ (DT) in the USA following the REMATCH trial, in which the HeartMate XVE (Thoratec, Pleasanton, CA, USA) pulsatile pump produced superior survival compared with medical therapy for terminal heart-failure patients [4]. With the emergence and evolution of continuous-flow (CF) technology, these small, durable pumps have nearly completely replaced the bulky, noisy, infection-prone pulsatile systems. Europe, and Germany in particular, has led the way in the introduction and maturation of CF technology in clinical practice. The evolving landscape of MCS in the USA has been chronicled through Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS), a database sponsored by the National Heart, Lung, and Blood Institute in a partnership with the Center for Medicare Services and the US Food and Drug Administration (FDA) [5]. Since the approval of HeartMate II by the FDA, pulsatile pumps have essentially disappeared from clinical practice for isolated left ventricular support. Following FDA approval of HeartMate II for BTT in 2008 and DT in 2010, the HeartWare ventricular assist device (HeartWare Corp., Framington, MA, USA) was approved for BTT in 2012. Since 2010, >99% of left ventricular assist devices (LVADs) implanted in the USA have employed CF technology [6]. In 2012 alone, nearly 2500 CF pumps were implanted in the USA, essentially equalling the total number of heart transplants [7]. The dramatic increment in survival with CF pumps compared with pulsatile systems is reflected in the US INTERMACS experience since 2006 (Fig. 1). The 1and 2-year survivals in the current era approach 80 and 70%, respectively. Of course, the majority of these pumps are currently implanted as BTT and therefore, do not directly expand the surgical support/ replacement options for end-stage heart failure. The spectrum of intended use of MCS is perhaps more easily examined in the USA than Europe because of the US regulatory requirement (possibly a disadvantage to clinicians) to commit to a strategy of either longterm permanent LVAD support (DT) or BTT at the time of implant. The approval of a CF pump for DT in the US set the stage for an increased surgical impact on advanced heart failure over that of heart transplantation alone. Between 2006 and 2011, DT implants represented only 18% of total LVAD implants in the USA; but in 2012, over 40% of implants were DT! [7] The artificiality of such designations is highlighted by the spectrum of ‘commitment’ to transplantation among centers/physicians implanting ventricular assist devices (VADs) for BTT over the past 4 years in the USA. Table 1 depicts the varying levels of commitment to transplant under the general category of BTT [7]; so much so that a totally ‘unofficial’ category of bridge to candidacy has emerged as a new part of the strategy repertoire. Even more indicative of the fluid nature of these designations is the movement of patients from one category to another as time elapses since implant, consistent with the well-known tendency for comorbidities to be modified by the haemodynamic impact of the VAD itself [5]. The platform for the expansion of long-term MCS is currently limited by the requirement for such patients in the USA to be transplant ineligible, a stipulation appropriate for a technology whose mid-term survival has never been competitive with cardiac transplantation. Recently, however, the door for including transplant-eligible patients has at least been unlocked, if not yet actually opened. Analyses from INTERMACS have identified patient subsets within the current DT population (generally poorer risk patients who have contraindications to transplantation) whose survival is 80% at 2 years, representing about 20% of non-urgent DT implants [8].