By Van Selby, MD
Assistant Professor of Medicine, UCSF Cardiology Division, Advanced Heart Failure Section, San Francisco
Dr. Selby reports no financial relationships relevant to this field of study.
SOURCE: Fiuzat M, et al. Heart rate or beta-blocker dose? Association with outcomes in ambulatory heart failure patients with systolic dysfunction: Results from the HF-ACTION trial. JACC Heart Failure 2015. doi:10.1016/j.jchf.2015.09.002.
Estep JD, et al. Risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients: Results from the ROADMAP study. J Am Coll Cardiol 2015 Oct 20;66:1747-1761.
Current guidelines recommend consideration of left ventricular assist devices (LVADs) for patients who have progressed to stage D heart failure (HF), at which point medical therapy is no longer effective. Most of the trials demonstrating the efficacy of LVADs have enrolled the sickest HF patients, often intravenous inotrope-dependent. No large study has compared LVAD to optimal medical management (OMM) in patients with ambulatory, non-inotrope-dependent HF.
The Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients (ROADMAP) study was a non-randomized, controlled, observational comparison of the HeartMate II LVAD and optimal medical management (OMM) in 200 patients with ambulatory New York Heart Association (NYHA) functional class IIIb (recent dyspnea at rest)-IV HF. All patients had an ejection fraction < 25%, at least one HF hospitalization in the previous year, and a 6-minute walk distance (6MWD) < 300 meters. Patients who had received any inotropes within the previous 30 days were excluded. The primary endpoint was a composite of survival and an improvement in 6MWD of at least 75 meters at 12 months.
Ninety-seven patients received an LVAD, and 103 opted for OMM. Patients in the LVAD group were more ill at baseline than those receiving OMM, as evidenced by a greater proportion with functional class IV symptoms (52% vs 25%), a greater proportion with Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 4, and lower health-related quality of life.
During 12 months of follow-up, more patients in the LVAD group met the primary endpoint (39% vs 21%, odds ratio, 2.4; P = 0.012). However, 18 patients in the OMM group received an LVAD during the follow-up period. In an as-treated analysis, patients receiving LVAD had greater 12-month survival (80 vs 63%, P = 0.02), but in an intention-to-treat analysis survival was not different between the two groups (81 vs 82%, P = 0.93). Those receiving LVADs also experienced more significant improvements in health-related quality of life (P < 0.001) and depression (P < 0.001) at 12 months.
Adverse events were significantly higher in the LVAD group (1.89 vs 0.83 events per patient-year). Bleeding was the most common complication in those receiving LVADs (47% of patients). Strokes occurred in 8.5% of the LVAD group and 2% of the OMM patients (P = 0.08). Rehospitalizations, mainly for recurrent heart failure in the OMM group and bleeding in the LVAD patients, were common in both groups (80% in LVAD, 62% in OMM; P < 0.001). The authors concluded that the ROADMAP results support the use of the HeartMate II LVAD in functionally limited, non-inotrope-dependent HF patients who have poor quality of life and meet FDA criteria for destination therapy LVAD.
According to recent INTERMACS data, approximately 80% of all LVADs are implanted in patients receiving inotropes at the time of implantation (profiles 1-3). However, data from contemporary registries show the slightly less sick non-inotrope-dependent HF patients with NYHA functional class IIIB-IV symptoms have a poor 12-month prognosis as well. As a result, there is growing interest in the use of LVADs among these patients, although data from large prospective trials are lacking. ROADMAP is, therefore, an important study that can help guide clinicians when discussing treatment options for patients with advanced, ambulatory HF.
There are several key messages in this article. The first is that earlier LVAD implantation is associated with improvements in functional capacity and quality of life. Patients improved with regard to functional class, 6MWD, depression, and health-related quality of life as measured by multiple scales. However, these improvements are offset by a substantially higher rate of complications associated with LVAD, including stroke, major bleeding, and rehospitalization. Taken together, the findings stress the need for thorough discussion of both risks and benefits in patients considering LVAD. Furthermore, the findings may help clinicians target patients expected to benefit most from LVAD implantation, such as those with particularly poor quality of life.
This study also reveals several important limitations. Patients were not randomized to LVAD vs OMM, and the results should not be considered conclusive. There was potential for bias, particularly related to patient selection. The use of an as-treated analysis for the primary outcome is somewhat unorthodox, and it is important to understand the intention-to-treat analysis found no significant survival benefit associated with earlier LVAD implantation. Finally, ROADMAP only evaluated the HeartMate II LVAD. As LVAD technology improves and we move to smaller, less invasive devices, the risk-benefit profiles defined in ROADMAP will probably differ.
Decisions regarding LVAD implantation and timing are complicated, especially for destination therapy. What ROADMAP tells us is that LVAD discussions can (and probably should) begin before patients reach the most advanced stages of heart failure. For those with severely reduced quality of life or depression, ROADMAP and other studies provide strong evidence that LVADs are associated with greater improvements in quality of life compared to medical therapy alone. But this discussion requires thorough evaluation of the risks associated with LVAD implantation as well. Ultimately, this is a patient preference-sensitive decision. ROADMAP can facilitate this discussion by comparing the risks associated with LVAD and medical therapy of advanced heart failure.