Growth Hormone Replacement Therapy in Heart Failure With Reduced Ejection Fraction: A Randomized, Double-Blind, Placebo-Controlled Trial.

Growth hormone deficiency (GHD) was present in 27% of consecutively screened HFrEF patients.

• 318 consecutive patients with HFrEF were screened.
• 86 patients (27%) fulfilled the criteria for GHD.
• Of the 86 GHD patients, 22 refused to participate, leaving 64 patients randomized.
• 30 patients were randomized to the active treatment group and 34 to the control group.

GH replacement therapy significantly improved peak oxygen consumption (peak VO2) compared to placebo after 1 year.

• Peak VO2 in the active group increased from 12.8 ± 3.4 mL/kg/min to 15.5 ± 3.15 mL/kg/min (P < 0.01).
• Delta peak VO2 between groups was +3.1 (active) vs -1.8 (placebo), P < 0.01.
• 45 patients completed the study: 24 in the active group and 21 in the control group.
• Peak VO2 was the primary endpoint of the trial.

GH replacement therapy improved multiple secondary cardiopulmonary exercise test parameters.

• Peak workload, VO2 at the aerobic threshold, O2 pulse, and VE/VCO2 slope all improved (P < 0.05).
• 6-minute walking test distance also improved significantly (P < 0.05).
• Handgrip strength improved significantly (P < 0.01).
• GH was administered at 0.012 mg/kg every second day (~2.5 IU) over 1 year.

GH replacement therapy significantly improved right ventricular function.

• TAPSE and TAPSE/pulmonary artery systolic pressure ratio both improved significantly (P < 0.01).
• This improvement in right ventricular function was observed on top of optimized background therapy.

GH replacement therapy improved clinical status and health-related quality of life.

• NYHA functional class improved significantly in the active group (P < 0.05).
• Minnesota Living With Heart Failure Questionnaire scores improved significantly (P < 0.05).
• NT-proBNP levels decreased significantly in the active group (P < 0.05).

Reduced activity of the GH/IGF-1 axis is common in heart failure and is associated with poor clinical status and outcomes.

• Growing evidence cited in the background suggests GHD is prevalent in HF populations.
• Preliminary results of GHD correction in HF had shown improvements in quality of life, cardiac structure and function, and cardiovascular performance prior to this trial.
• The present trial was designed as a double-blind, randomized, placebo-controlled study to rigorously evaluate these effects over 1 year.
• Patients enrolled were in NYHA functional class I, II, or III with concomitant GHD confirmed at screening.