Guido Carlomagno

Growth Hormone Deficiency in Patients with Chronic Heart Failure and Beneficial Effects of Its Correction

CONTEXT A reduced activity of the GH/IGF-I axis in chronic heart failure (CHF) has been described by several independent groups and is associated with poor clinical status and outcome. OBJECTIVE The aim of the current study was to investigate the prevalence of GH deficiency in a patient population with CHF and evaluate the cardiovascular effects of GH replacement therapy. DESIGN AND SETTING The randomized, single-blind, controlled trial was conducted at the Federico II University. PARTICIPANTS One hundred fifty-eight patients with CHF, New York Heart Association class II-IV, underwent a GH stimulation test. Sixty-three patients satisfied the criteria for GH deficiency, and 56 of them were enrolled in the trial. INTERVENTION The treated group (n = 28) received GH at a replacement dose of 0.012 mg/kg every second day (approximately 2.5 IU). MAIN OUTCOMES MEASURES Changes in physical performance and various cardiovascular indexes were measured. RESULTS GH replacement therapy improved quality of life score (from 46 +/- 5 to 38 +/- 4; P < 0.01), increased peak oxygen uptake and exercise duration (from 12.9 +/- .9 to 14.5 +/- 1 ml/kg x min and from 520 +/- 36 to 586 +/- 43 sec, respectively; P < 0.01), and flow-mediated vasodilation (from 8.8 +/- 1.3 to 12.7 +/- 1.2%; P < 0.01). GH increased left ventricular ejection fraction (from 34 +/- 2 to 36 +/- 2%; P < 0.01) and reduced circulating N-terminal pro-brain natriuretic peptide levels (from 3201 +/- 900 to 2177 +/- 720 pg/ml; P = 0.006). No significant changes from baseline were observed in controls. CONCLUSIONS As many as 40% of patients with CHF are GH deficient. GH replacement therapy in these patients improves exercise capacity, vascular reactivity, left ventricular function, and indices of quality of life.

A nutraceutical combination improves insulin sensitivity in patients with metabolic syndrome

AIM To test the efficacy of a proprietary nutraceutical combination in reducing insulin resistance associated with the metabolic syndrome (MetS). METHODS Sixty-four patients with MetS followed at a tertiary outpatient clinic were randomly assigned to receive either placebo or a proprietary nutraceutical combination (AP) consisting of berberine, policosanol and red yeast rice, in a prospective, double-blind, placebo-controlled study. Evaluations were performed at baseline and after 18 wk of treatment. The homeostasis model assessment of insulin resistance (HOMA-IR) index was the primary outcome measure. Secondary endpoints included lipid panel, blood glucose and insulin fasting, after a standard mixed meal and after an oral glucose tolerance test (OGTT), flow-mediated dilation (FMD), and waist circumference. RESULTS Fifty nine patients completed the study, 2 withdrew because of adverse effects. After 18 wk there was a significant reduction in the HOMA-IR index in the AP group compared with placebo (ΔHOMA respectively -0.6 ± 1.2 vs 0.4 ± 1.9; P < 0.05). Total and low density lipoprotein cholesterol also significantly decreased in the treatment arm compared with placebo (Δlow density lipoprotein cholesterol -0.82 ± 0.68 vs -0.13 ± 0.55 mmol/L; P < 0.001), while triglycerides, high density lipoprotein cholesterol, and the OGTT were not affected. In addition, there were significant reductions in blood glucose and insulin after the standard mixed meal, as well as an increase in FMD (ΔFMD 1.9 ± 4.2 vs 0 ± 1.9 %; P < 0.05) and a significant reduction in arterial systolic blood pressure in the AP arm. CONCLUSION This short-term study shows that AP has relevant beneficial effects on insulin resistance and many other components of MetS.

Epoetin alfa increases frataxin production in Friedreich's ataxia without affecting hematocrit

Objective of the study was to test the efficacy, safety, and tolerability of two single doses of Epoetin alfa in patients with Friedreichs ataxia. Ten patients were treated subcutaneously with 600 IU/kg for the first dose, and 3 months later with 1200 IU/kg. Epoetin alfa had no acute effect on frataxin, whereas a delayed and sustained increase in frataxin was evident at 3 months after the first dose (+35%; P < 0.05), and up to 6 months after the second dose (+54%; P < 0.001). The treatment was well tolerated and did not affect hematocrit, cardiac function, and neurological scale. Single high dose of Epoetin alfa can produce a considerably larger and sustained effect when compared with low doses and repeated administration schemes previously adopted. In addition, no hemoglobin increase was observed, and none of our patients required phlebotomy, indicating lack of erythropoietic effect of single high dose of erythropoietin.

Serum soluble ST2 and interleukin-33 levels in patients with pulmonary arterial hypertension

arterial hypertension Guido Carlomagno , Giancarlo Messalli , Rosa Marina Melillo , Anna Agnese Stanziola , Carla Visciano , Valentina Mercurio , Massimo Imbriaco , Stefano Ghio , Matteo Sofia , Domenico Bonaduce , Serafino Fazio a,⁎ a Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Federico II University — Naples, Italy b Department of Biomorphological and Functional Sciences, Federico II University — Naples, Italy c Department of Cellular and Molecular Biology and Pathology “L. Califano”, Federico II University — Naples, Italy d Department of Respiratory Diseases, Federico II University — Naples, Italy e Department of Cardiology, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy

Insulin resistance: Is it time for primary prevention?

Insulin resistance is a clinical condition characterized by a decrease in sensitivity and responsiveness to the metabolic actions of insulin, so that a given concentration of insulin produces a less-than-expected biological effect. As a result, higher levels of insulin are needed to maintain normal glucose tolerance. Hyperinsulinemia, indeed, is one of the principal characteristics of insulin resistance states. This feature is common in several pathologic conditions, such as type 2 diabetes, obesity, and dyslipidemia, and it is also a prominent component of hypertension, coronary heart disease, and atherosclerosis. The presence of endothelial dysfunction, related to insulin resistance, plays a key role in the development and progression of atherosclerosis in all of these disorders. Insulin resistance represents the earliest detectable abnormality in type 2 diabetes, and is one of the major underlying mechanisms of hypertension and cardiovascular diseases. Its early detection could be of great importance, in order to set a therapeutic attack and to counteract the higher risk of diabetes and cardiovascular diseases.

Response to pulmonary vasodilator treatment in a former smoker with combined interstitial lung disease complicated by pulmonary hypertension: Case report and review of the literature

We describe a 76-year-old former smoker with a diagnosis of combined pulmonary fibrosis and emphysema associated with pulmonary hypertension and rapidly progressive right heart failure, in whom combined treatment with sitaxsentan and sildenafil resulted in sustained improvement of his clinical condition and exercise performance, without any relevant adverse events. Combined pulmonary fibrosis and emphysema comprises a recently identified syndrome, probably related to tobacco use, and characterized by the coexistence of upper-lobe emphysema and fibrotic changes of the lower lobes, preserved lung volumes, significant hypoxemia, and a high prevalence of pulmonary hypertension, resulting in severe dyspnea. To date, no prospective series, to the best of our knowledge, has reported on the effects of pulmonary vasodilator therapy in such patients.

The Importance of Tricuspid Regurgitation and Right Ventricular Overload in ICD/CRT Recipients: Beside the Left, beyond the Left

Device therapy for advanced heart failure has become increasingly employed in the last 10 years. Several retrospective studies have postulated a harmful effect of implantable cardioverter‐defibrillator (ICD) lead placement on tricuspid valve function and right heart hemodynamics, in particular among patients with preexisting pulmonary vascular overload and both left and right ventricular remodeling/dysfunction. This functional hypothesis is also supported by long‐term clinical follow‐up analyses of ICD and cardiac resynchronization therapy recipients. In this viewpoint, we propose that the possibility of worsening tricuspid regurgitation and consequent hemodynamic deterioration following device implantation should be considered in future studies, as well as in the preimplant evaluation of individual candidates among other clinical factors. (PACE 2011; 34:1181–1184)

Hemodialysis does not affect ventricular–arterial coupling beyond the reduction of blood pressure and preload

blood pressure and preload Laura Sasso , Alfredo Capuano , Maristella Minco , Antonella Paglia , Flora Pirozzi , Bruno Memoli , Guido Carlomagno , Mario Petretta , Domenico Bonaduce a,⁎ a Department of Clinical Medicine, Cardiovascular and Immunological Sciences, Division of Internal Medicine, Federico II University, Naples, Italy b Department of Pathology, Division of Nephrology, Federico II University, Naples, Italy

Endocrine Alterations Are the Main Determinants of Cardiac Remodelling in Restrictive Anorexia Nervosa

Objective. Anorexia nervosa is a condition of reduced hemodynamic load, characterized by varying degrees of cardiac remodelling, only in part related to reduced body mass; the mechanism for such variability, as well as its clinical significance, remains unknown. Aim of the study was to assess the possible influence of a great number of clinical, biochemical, and endocrine factors on cardiovascular parameters in restrictive anorexia nervosa. Method. Twenty-five female patients hospitalized for restrictive anorexia nervosa underwent extensive cardiovascular, clinical, and biochemical evaluation. Results. Height-adjusted and cardiac workload-matched left ventricular mass was significantly related to several endocrine parameters, blood pressure, and vasoreactivity. On multivariate analysis, IGF/GH ratio and systolic blood pressure were the only independent predictors of height-adjusted ventricular mass (adj-R 2 = 0.585; P = 0.001); when matching for cardiac workload, left ventricular mass was independently predicted only by GH and FT3 levels. All effects were independent of patients weight and BMI. Conclusions. Indices of endocrine impairment seem to be the most relevant determinants of left ventricular hypotrophy in anorectic patients, apparently independent of reduced hemodynamic load and BMI. In particular, IGF/GH ratio and FT3 seem to particularly affect left ventricular mass in this population.

Long term combination treatment for severe idiopathic pulmonary arterial hypertension

We report the long-term follow-up of 3 cases of severe idiopathic pulmonary arterial hypertension, in whom tadalafil plus sitaxentan combination therapy improved the clinical condition and exercise performance without any relevant adverse event.