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Growth Hormone May Boost Heart Function, Too

— Giving growth hormone to deficient patients with chronic heart failure may slow progression of the condition, researchers found.

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Giving growth hormone to deficient patients with chronic heart failure may slow progression of the condition, researchers found.

In a small, single-center study, heart failure patients who had growth hormone replacement had a significant increase in peak oxygen consumption over 4 years compared with controls (increase of 7.1 ml/kg/min versus a decrease of 1.8 ml/kg/min), Antonio Cittadini, MD, of the University of Naples in Italy, and colleagues reported online in the Journal of the American College of Cardiology.

"Although this is a preliminary study, the finding suggests a new therapeutic approach to a large proportion of growth-hormone-deficient patients with chronic heart failure," they wrote.

Previous research suggests that growth hormone deficiency affects nearly 40% of patients with chronic heart failure, and growth hormone replacement in the short term improves cardiac function -- although some studies have shown cardiac risks with regular growth hormone replacement.

It is unclear if long-term growth hormone replacement also affects progression of heart failure, so Cittadini and colleagues conducted an extension of a randomized, controlled, single-blind trial that screened 158 patients with heart failure -- New York Heart Association classes II to IV -- and identified 63 patients who had growth hormone deficiency.

A total of 56 of these patients were then randomized to either growth hormone therapy or standard treatment for heart failure, and were assessed at baseline and again at 4-year follow-up.

Growth hormone was administered as subcutaneous somatropin (rDNA origin) for injection at a dose of 0.012 mg/kg every second day.

The primary endpoint was peak oxygen consumption (VO2), which was chosen given its utility as a strong predictor of heart failure progression. Secondary endpoints included left ventricular ejection fraction and volumes, quality of life, and safety.

Overall, 17 patients in the growth hormone group and 14 controls completed the study.

Cittadini and colleagues found significant effects of growth hormone therapy for several outcomes (P<0.001 for all).

In terms of the primary endpoint, peak oxygen consumption increased "remarkably" over 4 years in the growth hormone group, to 21 ml/kg/min compared with 11.8 ml/kg/min in controls -- translating to an increase of 7.1 ml/kg/min for treated patients compared with a decrease of 1.8 ml/kg/min among controls.

Growth hormone also induced left ventricular reverse modeling, with significant reductions in both left ventricular end-diastolic and end-systolic volumes indexes, they wrote.

Left ventricular ejection fraction rose by 10% in the growth hormone group compared with a decline of 2% in controls, and the treatment effect on left ventricular end-systolic volume index was -22 ml/m2 for the growth hormone group compared with an increase of 8 ml/m2 for controls.

"The improvements in left ventricular end-systolic volume and ejection fraction were equally relevant; both are consolidated predictors of survival," they researchers wrote, adding that all of the findings were similar in sensitivity analyses.

There were no major adverse events among patients who received growth hormone, although two patients on the drug reported arthralgia, a common complication of these agents.

The researchers noted that hospitalizations for worsening heart failure were lower in the growth hormone group than in the control group (11 patients versus 20 patients), writing that "although the study was not designed for hard clinical endpoints, it was noteworthy that there was a marked difference in the aggregate of death and hospitalization for worsening heart failure."

Long-term growth hormone replacement may involve "radical changes in the intimate mechanisms that mediate the progression of congestive heart failure," but larger and longer trials are needed because the current study was limited, particularly by its small size and its single-center, single-blind design.

Disclosures

The study was supported in part by a grant from Merck Serono and Ipsen.

A co-author reported being an employee of Merck Serono.

The other authors reported no conflicts of interest.

Primary Source

Journal of the American College of Cardiology: Heart Failure

Source Reference: Cittadini A, et al "Growth hormone replacement delays the progression of chronic heart failure combined with growth hormone deficiency" J Am Coll Cardiol 2013; DOI: 10.1016/j.jchf.2013.04.003.