100% 5-year survival on HeartMate 3 LVAD: new reality, or a mirage?

In this article, Schmitto et al. [1] present 5-year outcomes of the initial 8 patients from the HeartMate 3™ CE Mark Clinical Trial. Authors should be congratulated on their excellent results—not only did all 8 patients survive, but also no right heart failure, haemolysis, pump thrombosis, mechanical pump malfunction or neurologic events occurred. The low patient number does limit the comparability and extrapolability of the authors’ excellent outcomes. The CE mark trial itself, to which these patients belonged to, observed a 2-year survival of 74% [2]. Survival of 8/8 results in quite broad 95% confidence intervals: 63–100%, which is also the case with other outcomes mentioned above. With this in mind, the comparative survival plot in the central image should be interpreted with caution. We would like to draw a comparison to our own outcomes of early HeartMate II left ventricular assist device (LVAD) implants at University of Rochester (2006–2010) where we achieved a 2-year survival of 92% in 52 patients (Fig. 1, red curve), compared to 63% 2-year survival in the nationwide HeartMate II LVAD population nationwide (Fig. 1, black curve). Outcomes of early HeartMate II LVAD implants at University of Rochester (Rochester, NY, USA) as compared to the nationwide outcomes from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database between 2006–2010. When reviewing survival with different LVAD generations, we observe progressive improvement from HeartMate XVE to HeartMate II and finally to HeartMate 3 LVAD [3]. In reference to HeartMate II LVAD alone, we would like to point out that over a decade, the outcomes progressively improved without significant device reengineering, Specifically, the 2-year survival improved from 58% in 2009 to 76% in 2019—an 18% survival benefit in 10 years. In the absence of major device modifications, this gain can only be explained by significant alterations in patient selection and management. Justifiably based on risk–benefit analysis, the expansion of mechanical circulatory support (MCS) into less sick patients has correspondingly led to an incremental decrease in functional capacity gain. Qualitatively, this is best judged by the 6-min walk test (6MWT) performance over time (Fig. 1). Two factors deserve attention here. (1) Median baseline 6MWT is already high at 351 m. Normal 6MWT ranges from 400 to 700 m [4]. To draw another parallel to early HeartMate II LVAD implants, the pivotal Bridge to Transplant trial reported mean baseline 6MWT of 42 m, and only 25 out of 133 patients (18.8%) were able to participate in the test, emphasizing the severity of these patients' condition. After 3 months, this distance improved to 292 m [5], resulting in the ‘gain’ of 250 m—a 595% improvement. In the later Destination Therapy trial, the mean baseline 6MWT was 182 m, which improved to 319 m [6]—this would be the ‘gain’ of 137 m, or 75%. In this report, the maximum ‘gain’ was 84 m (from 351 to 435 m at 2 years), or 24%. The reason for ‘maxing out’ functional gain and the inability to achieve normal functional capacity remain unclear. However, certain factors such as lack of demand responsiveness at the fixed flow rate should at least partially explain this ‘glass ceiling’ effect. (2) Afterwards, even though the 6MWT drops over time back to baseline, the baseline 6MWT performance was already quite good and better than the 3-month 6MWT in the HeartMate II pivotal Bridge to Transplant and Destination Therapy trials. The apparent decline in the quality of life (QoL) in the long term implies that there are other, more ‘fuzzy’ factors at play, perhaps including a late-onset right ventricle (RV) dysfunction. The rather high driveline infection rate of 0.25 events per patient-year despite all the appropriate precaution and care [7] remains discouraging, however, not surprising. This further reinforces its reputation as the most negatively perceived LVAD-related complication [8]. We could not agree more that the driveline elimination remains the next major milestone not only for the patient QoL, but (more importantly) the event-free survival. MCS as a value proposition will be judged on continued advancement in risk mitigation and QoL improvement as the field moves into higher INTERMACS profiles. The bar has certainly been raised by this study and its unparalleled outcomes.