Growth Hormone Replacement Therapy in Heart Failure With Reduced Ejection Fraction

Growing evidence suggests that reduced activity of the growth hormone (GH)/insulin-like growth factor (IGF)-1 axis is common and associated with poor clinical status and outcome in heart failure (HF). In addition, preliminary results of growth hormone deficiency (GHD) correction in HF showed an improvement in quality of life, cardiac structure and function, and cardiovascular performance. The aim of the present double-blind, randomized, placebo-controlled trial was to evaluate the cardiovascular effects of 1 year of GH replacement therapy in a cohort of patients with heart failure and reduced ejection fraction (HFrEF). Consecutive patients with HFrEF in NYHA functional class I/II/III and concomitant GHD were recruited. GHD patients were randomized to receive GH (0.012 mg/kg every second day ∼2.5 IU), or placebo, on top of background therapy. The primary endpoint was peak oxygen consumption (VO2). Secondary endpoints included hospitalizations, end-systolic left ventricular volumes, N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, health-related quality of life score, and muscle strength (handgrip). A total of 318 consecutive patients were screened, with 86 (27%) fulfilling the criteria for GHD. Of these, 22 subjects refused to participate in the study. The final study groups consisted of 64 patients, 30 randomized in the active treatment group and 34 in the control group. After 1 year, 45 patients completed the study (21 in the control group and 24 in the active group). A statistically significant improvement of peak VO2 was reached in the active group (from 12.8 ± 3.4 mL/kg/min to 15.5 ± 3.15 mL/kg/min; P < 0.01; delta peak VO2 between groups: +3.1 vs -1.8; P < 0.01). Other cardiopulmonary exercise test parameters (ie, peak workload, VO2 at the aerobic threshold, O2 pulse and VE/VCO2 slope; P < 0.05) also improved, paralleled by an increase in 6-minute walking test distance (P < 0.05) and handgrip strength (P < 0.01). GH improved right ventricular function (ie, TAPSE and TAPSE/pulmonary artery systolic pressure ratio; P < 0.01), leading to an amelioration of clinical status (NYHA functional class; P < 0.05) and health-related quality of life (Minnesota Living With Heart Failure Questionnaire; P < 0.05). A significant decrease of NT-proBNP was also found (P < 0.05). This randomized, double-blind, placebo-controlled trial demonstrates that GH replacement therapy in HFrEF patients with GHD improves exercise performance, and left ventricular and right ventricular structure and function, leading to an amelioration of clinical status and health-related quality of life. (Treatment of GHD Associated With CHF; NCT03775993).