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Growth hormone therapy improved exercise capacity, heart function, and quality of life in patients with HFrEF and growth hormone deficiency.

Correcting growth hormone deficiency (GHD) in patients with heart failure with reduced ejection fraction (HFrEF) may lead to meaningful improvements in both functional capacity and cardiac performance, according to findings published in JACC: Heart Failure.

The double-blind, randomized, placebo-controlled trial adds to a growing body of evidence implicating the GH/insulin-like growth factor (IGF)-1 axis in the pathophysiology and clinical course of heart failure.

“We have previously shown that approximately 20% to 25% of [chronic heart failure] patients display GHD,” wrote Alberto Maria Marra, MD, PhD, and colleagues. “There is a scientific background to consider [chronic heart failure] as an appropriate clinical context to screen for GHD and to perform replacement GH therapy in adult patients, also considering the well-known growth-promoting, antiapoptotic, and nitric oxide–mediated vasodilating actions of the GH/IGF-1 axis.”

Among 318 patients with HFrEF screened for the study, 86 (27%) were found to have concomitant GHD. After accounting for 22 patient refusals, mostly related to COVID-19 lockdowns, the researchers randomized 64 participants to receive either GH replacement therapy or placebo in addition to standard guideline-directed medical therapy. GH was administered at a dose of 0.012 mg/kg every other day (approximately 2.5 IU).

The trial’s primary endpoint, peak oxygen consumption (VO₂), improved significantly in the GH group over 12 months, from 12.8 to 15.5 mL/kg/min (P<0.01). Meanwhile, the placebo group experienced a decline (delta peak VO₂: +3.1 vs −1.8; P<0.01). Several additional cardiopulmonary exercise test parameters also favored the active treatment arm, including peak workload, oxygen pulse, VE/VCO₂ slope, and VO₂ at the aerobic threshold (all P<0.05).

Functional status and muscular performance improved in parallel. GH-treated patients showed gains in 6-minute walk test distance (P<0.05) and handgrip strength (P< 0.01), as well as a significant improvement in New York Heart Association functional class (P<0.05).

Cardiac remodeling and biomarker data reinforced these functional benefits. Patients receiving GH therapy experienced improvement in right ventricular function as measured by tricuspid annular plane systolic excursion (TAPSE) and the TAPSE/pulmonary artery systolic pressure ratio (P< 0.01). In addition, the GH arm showed a reduction in N-terminal pro–B-type natriuretic peptide levels, a well-established marker of HF severity (P<0.05).

Patient-reported outcomes also favored GH treatment. The Minnesota Living With Heart Failure Questionnaire score improved significantly in the GH group (P<0.05), suggesting not only better physiological performance but also perceived well-being.

While the final analysis included only 45 patients who completed the full year of therapy (21 in the placebo group and 24 in the GH group), the researchers emphasized that their trial was robustly designed and showed significant results.

“Of note, these results were observed on top of guideline-directed medical therapy with a considerable proportion of patients taking new-generation drugs (angiotensin receptor neprilysin inhibitor, SGLT2i). Consequently, if confirmed by larger studies, our results suggest that HFrEF represents an appropriate clinical context in which GHD should be screened, being a common and treatable condition with an available safe and effective replacement therapy,” Dr. Marra and colleagues concluded. “On the other hand, the same approach is routinely employed for other HF-associated deficiencies, such as iron deficiency.”