Effects of growth hormone on exercise capacity and cardiopulmonary performance in patients with chronic heart failure.

BACKGROUND: Because GH exerted beneficial effects in various experimental models of heart failure, we investigated the effects of GH on physical exercise capacity and cardiopulmonary performance in patients with dilated cardiomyopathy and chronic heart failure (CHF). METHODS: Twenty-two patients with CHF (New York Heart Association functional class II-III) underwent spirometry and a symptom-limited, cardiopulmonary exercise testing before and after 3 months of GH (n = 11; seven males; seven idiopathic; 57 +/- 11 yr; 4 IU sc every other day) or placebo (n = 11; eight males; six idiopathic; 54 +/- 10 yr) administration, in a randomized, double-blind trial. Background CHF therapy remained unchanged. RESULTS: GH, but not placebo, increased IGF-I serum concentration (from 144 +/- 35 to 293 +/- 58 ng/ml; P < 0.005) and improved New York Heart Association functional class (from 2.4 +/- 0.5 to 1.8 +/- 0.4; P < 0.005), exercise duration (from 831 +/- 273 to 925 +/- 266 sec; P < 0.005), peak power output (from 245 +/- 127 to 280 +/- 132 W; P < 0.05), peak minute ventilation (from 52.5 +/- 16.1 to 61.3 +/- 17.3 liters/min; P < 0.05), peak oxygen consumption (from 19.8 +/- 5.6 to 25.1 +/- 5.6 ml/kg.min; P < 0.005), and anaerobic threshold (from 14.9 +/- 4.8 to 20.0 +/- 4.5 ml/kg.min; P < 0.005) without affecting lung function parameters. Furthermore, the slope of the relationship between minute ventilation and pulmonary carbon dioxide production (ventilatory efficiency) decreased from 34.7 +/- 5.1 to 31.7 +/- 5.3 (P < 0.005), whereas the slope of the relation between percent predicted heart rate reserve used and percent observed metabolic reserve used (chronotropic index) rose from 0.57 +/- 0.20 to 0.69 +/- 0.18 (P < 0.005). CONCLUSION: Given the predictive value of physical exercise capacity and cardiopulmonary performance in CHF progression, these data provide additional insights into the mechanisms by which GH may potentially benefit CHF patients

The uncontrolled clinical trial: scientific, ethical, and practical reasons for being.

According to principles of clinical trial design, the demonstration of efficacy of a new treatment is based on comparing the response in the treated group with that of a control group receiving placebo or another active treatment. The need for a control group is also recommended by the major international institutions that govern the ethics and the practice of clinical research. Despite these principles and recommendations, inspection of a purposive sample of ongoing clinical trials listed in the NIH registry ( http://ClinicalTrials.gov ) reveals that as many as one-third of trials are uncontrolled. Since these trials were approved through a formal evaluation by ethics committees, the lack of adequate control was not perceived as a major deficiency in the study design. Most uncontrolled trials belong to the oncology/hematology area. If two extreme disease conditions for nature and progression are analyzed, such as acute myeloid leukemia (AML) and chronic heart failure (CHF), the difference in the prevalence of uncontrolled trials is very striking. The number of uncontrolled trials is only 13\% in CHF, whereas it reaches 66\% in the AML group. I believe that the underlying disease condition plays a primary role in orienting the design of the study: oncology and hematology may be fields in which uncontrolled studies are common, whereas in other fields, e.g., cardiology, this phenomenon can be reduced. Within the limitations of the selection process of the examined trials, the current analysis indicates that the clinical trial reality does not strictly follow experimental design theory and official recommendations

Heart failure as a multiple hormonal deficiency syndrome.

The MHD model extends the classic neurohormonal theory and its application by focusing on restoring HF-related metabolic or hormonal deficiencies. Each component of MHD is associated with impaired functional capacity and poor clinical outcome. However, the replacement approaches so fat attempted have provide additional benefits on top of standard therapy. There are no data regarding the crucial questionof whether life expectancy is also improved. The evidence presented in this review strongly suggests that MHD is not a simple disease marker or a compensatory response. Even assuming that it originates as an adaptive reaction, ultimately, each hormonal deficiency is associated with reduced functional capacity and, more importantly, is a powerful and independent predictor of poor clinical outcome. This finding in itself justifies the implementation of robust clinical trials to determine whether either single or multiple hormone replacement is a workable strategy to adopt in HF patients in addition to current pharmacotherapy