Effect of Inotropes on Patient-Reported Health Status in End-Stage Heart Failure

Background: A growing population of patients with end-stage heart failure (HF) with reduced ejection fraction has limited treatment options to improve their quality and quantity of life. Although positive inotropes have failed to show survival benefit, these agents may enhance patient-reported health status, that is, symptoms, functional status, and health-related quality of life. We sought to review the available clinical trial data on positive inotrope use in patients with end-stage HF and to summarize evidence supporting the use of these agents to improve health status of patients with end-stage HF. Methods: A literature review of randomized controlled trials examining the use of positive inotropy in HF with reduced ejection fraction was conducted. We searched MEDLINE, SCOPUS, and Web of Science between January 1980 to December 2018 for randomized controlled trials that used as their main outcome measures the effects of inotrope therapy on (1) morbidity/mortality, (2) symptoms, (3) functional status, or (4) health-related quality of life. Inotropes of interest included adrenergic agents, phosphodiesterase inhibitors, calcium sensitizers, myosin activators, and SERCA2a (sarcoplasmic reticulum Ca 2+ -ATPase) modulators. Results: Twenty-two out of 26 inotrope randomized controlled trials measured the effect of inotropes on at least one patient-reported health status domain. Among the 22 studies with patient-related health status outcomes, 11 (50%) gauged symptom response, 15 (68%) reported functional capacity changes, and 12 (54%) reported health-related quality of life measures. Fourteen (64%) of these trials noted positive outcomes in at least one health status domain measured; 11 (79%) of these positive studies used agents that worked through phosphodiesterase inhibition. Conclusions: There has been a lack of standardization surrounding measurement of patient-centered outcomes in studies of inotropes for end-stage HF with reduced ejection fraction. The degree to which positive inotropes can improve patient-reported health status and the adverse risk they pose remains unknown.