Growth Hormone and Heart Failure: Implications for Patient Stratification, Prognosis, and Precision Medicine

Heart failure (HF) remains a major cause of morbidity and mortality worldwide. While standard treatments primarily target neurohormonal pathways, emerging evidence highlights the significant role of hormonal deficiencies, such as impaired growth hormone (GH) signaling, in HF progression and outcomes. GH is crucial for cardiovascular and skeletal muscle function, and its deficiency has been associated with worse prognosis. This review synthesizes recent findings from randomized controlled trials (RCTs) to explore how GH can contribute to personalized care and improve patient stratification in HF. A comprehensive literature review was conducted using PubMed up to 10 October 2024. Search terms included "growth hormone" combined with "heart failure", "HFrEF", "HFpEF", and "HFmrEF." Only placebo-controlled RCTs published in English and involving human subjects were considered. Data on study design, participant characteristics, GH dosing, and key clinical outcomes were systematically extracted and analyzed. Several trials demonstrated that GH therapy can transiently improve left ventricular ejection fraction (LVEF), exercise capacity, and reduce inflammatory markers. For example, one study has reported an increase in LVEF from 32 +/- 3.8% to 43.8 +/- 4.6% (p = 0.002), following three months of GH therapy in post-MI HF patients. However, benefits diminished after discontinuation. Additional studies have observed sustained improvements in peak oxygen consumption and LVEF over four years, with an additional trend towards hard endpoint improvement. Conversely, some studies showed no significant impact on cardiac function, highlighting heterogeneity in outcomes. As a result, GH therapy holds promise for improving cardiac and functional parameters in HF patients, but evidence remains mixed. Larger, long-term RCTs are needed to confirm its efficacy and safety. Precision medicine approaches and biomarker-driven strategies may optimize patient outcomes and guide clinical practice.