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GH Therapy in Chronic Heart Failure: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Nikolaos Theodorakis1,2,3, Georgios Feretzakis3, Magdalini Kreouzi4
1Department of Cardiology & Heart Failure Outpatient Clinic, Sismanogleio-Amalia Fleming General Hospital, Melissia 15127, Greece.
Insights
Growth hormone (GH) therapy shows promise for heart failure (HF) patients, improving cardiac function and exercise capacity. Further event-driven trials are necessary to confirm its impact on hard clinical outcomes.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Guideline-directed medical therapy for heart failure (HF) primarily addresses neurohormonal activation.
- Growth hormone (GH) deficiency is linked to poorer outcomes in HF patients.
- GH therapy is being explored for multiple hormonal deficiency syndromes associated with HF.
Purpose of the Study:
- To evaluate the efficacy and safety of growth hormone (GH) therapy in adult patients with heart failure (HF).
Main Methods:
- A systematic literature search was performed across PubMed, Cochrane Library, and ClinicalTrials.gov, adhering to PRISMA guidelines.
- Included were randomized, placebo-controlled trials of GH therapy in adult HF patients; 17 studies met the criteria.
- Study quality was assessed by independent reviewers, focusing on randomization, blinding, and placebo control.
Main Results:
- GH therapy significantly improved left ventricular ejection fraction (+3.34%) and peak oxygen consumption (+2.84 mL/kg/min).
- New York Heart Association class improved (–0.44), and GH therapy reduced the composite endpoint of death, worsening HF, or ventricular tachycardia by 41%.
- Subgroup analyses revealed greater benefits in patients with ischemic cardiomyopathy, higher baseline ejection fraction, and longer treatment durations.
Conclusions:
- GH therapy demonstrates significant improvements in cardiac function, exercise capacity, and HF symptoms.
- A statistically significant trend towards improved hard clinical endpoints was observed.
- Event-driven trials are recommended to validate these findings and confirm the long-term impact of GH therapy in HF.
Context:
Guideline-directed medical therapy of heart failure (HF) primarily targets neurohormonal activation. However, GH has emerged as a potential treatment for the multiple hormonal deficiency syndrome, which is associated with worse outcomes in HF.
Objective:
This study evaluates the efficacy and safety of GH therapy in HF.
Data Sources:
A systematic search was conducted in PubMed, Cochrane Library, and ClinicalTrials.gov, according to PRISMA guidelines.
Study Selection:
Randomized, placebo-controlled trials studying GH therapy in adult HF patients were included. Of the 1184 initially identified records, 17 studies (1.4%) met the inclusion criteria.
Data Extraction:
Two independent authors conducted the search, with any disagreements resolved by a third author. Study quality was assessed using predefined criteria, including randomization, blinding, and the presence of a placebo group.
Data Synthesis:
A random-effects model was applied due to heterogeneity across studies. GH therapy significantly improved left ventricular ejection fraction (+3.34%; 95% CI, 1.09-5.59; P = .0037), peak oxygen consumption (+2.84 mL/kg/min; 95% CI, 1.32-4.36; P = .0002), and New York Heart Association class (-0.44; 95% CI, -0.08 to -0.81; P = .023). GH therapy also reduced the composite of death, worsening HF or ventricular tachycardia by 41% (RR = .59; 95% CI, 0.39-0.90; P = .013). Subgroup analyses indicated that patients with ischemic cardiomyopathy, baseline ejection fraction ≥30%, and longer treatment duration experienced greater benefits.
Conclusion:
GH therapy demonstrated improvements in cardiac function, exercise capacity, and HF symptoms, along with a statistically significant trend toward improvements in hard endpoints. Event-driven trials are needed to validate these findings.
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