Emanuele Bobbio

Complementary therapeutic effects of dual delivery of insulin-like growth factor-1 and vascular endothelial growth factor by gelatin microspheres in experimental heart failure

Strategies to prevent adverse left ventricular (LV) remodelling after myocardial infarction have included several traditional approaches and novel cell‐based or gene therapies. Delivery of growth factors in post‐infarction heart failure has emerged as a valuable alternative strategy. Our aim was to investigate the effects of sequential release of vascular endothelial growth factor (VEGF) and insulin‐like growth factor‐1 (IGF‐1) from biodegradable gelatin microspheres in experimental heart failure.

Growth Hormone Replacement Delays the Progression of Chronic Heart Failure Combined With Growth Hormone Deficiency An Extension of a Randomized Controlled Single-Blind Study

OBJECTIVES This study sought to evaluate the efficacy and safety of long-term growth hormone (GH) replacement therapy in GH-deficient patients with chronic heart failure (CHF). BACKGROUND Recent evidence indicates that growth hormone deficiency (GHD) affects as many as 40% of patients with CHF, and short-term GH replacement causes functional benefit. Whether long-term GH replacement also affects CHF progression is unknown. METHODS The study is an extension of a previous randomized, controlled single-blind trial that screened 158 consecutive CHF patients (New York Heart Association classes II to IV) and identified 63 who had GHD by the growth hormone releasing hormone plus arginine test. Fifty-six patients were randomized to receive either GH therapy or standard CHF therapy. Patients were evaluated at baseline and after a 4-year follow-up. The primary endpoint was peak oxygen consumption (VO2). Secondary endpoints included left ventricular (LV) ejection fraction and volumes, serum amino terminal fragment of the pro-hormone brain-type natriuretic peptide, quality of life, and safety. RESULTS Seventeen patients in the GH group and 14 in the control group completed the study. In the GH group, peak VO2 improved over the 4-year follow-up. The treatment effect was 7.1 ± 0.7 ml/kg/min versus -1.8 ± 0.5 ml/kg/min in the GH and control groups, respectively. At 4 years, LV ejection fraction increased by 10 ± 3% in the GH group, whereas it decreased by 2 ± 5% in control patients. The treatment effect on LV end-systolic volume index was -22 ± 6 ml and 8 ± 3 ml/m(2) in the GH and control groups, respectively (all p < 0.001). No major adverse events were reported in the patients who received GH. CONCLUSIONS Although this is a preliminary study, the finding suggests a new therapeutic approach to a large proportion of GHD patients with CHF.

The GH/IGF-1 Axis in Chronic Heart Failure

The classic model of Chronic Heart Failure (CHF) is rooted in the overexpression of neurohormonal molecules. To complement this paradigm, increasing evidence indicates that a variety of hormones may be down-regulated in CHF patients. The list includes growth hormone (GH) and its tissue effector insulin-like growth factor-1 (IGF-1). The GH/IGF-1 axis regulates cardiac growth, stimulates myocardial contractility, and influences the vascular system. The relationship between the GH/IGF-1 axis and the cardiovascular system has been extensively demonstrated in numerous studies in animals models and confirmed by the cardiac derangements secondary to both GH excess and deficiency in humans. Impaired activity of the GH/IGF-1 axis in CHF has been described by several independent groups and includes a wide array of abnormalities, including low IGF-1 levels, GH deficiency (GHD), and GH resistance that may be related to the severity of heart disease. According to several observations, these derangements are associated with poor clinical status and outcome. Since the first study of GH therapy in CHF in 1996, several placebo-controlled trials have been conducted with conflicting results. These discordant findings are likely explained by the degree of CHF-associated GH/IGF-1 impairment that may impact on individual responsiveness to GH administration. Biological actions of GH and IGF-1, cardiovascular implication of GH deficiency and GH excess, relation between somatotrophic axis and CHF are discussed. Results from trials of GH therapy, emerging therapeutic strategies, safety issues, and lack in evidence are also reported.

An unusual case of dilated cardiomyopathy associated with partial hypopituitarism

Dilated cardiomyopathy (DCM) secondary to endocrinologic disease occurs rarely. In a large clinicopathological review of 673 patients, only 1.5% fall in the metabolic category, mostly due to thyroid disorders [1]. Sporadic reports of DCM associated with other endocrinopathies have been subsequently published including acromegaly, GH deficiency, pheochromocytoma, hypoparathyroidism, Sheehan syndrome, and Addison’s disease. We herein describe a rare case of DCM secondary to partial hypopituitarism, in turn related to a previous intracranial surgery, promptly responding to multiple hormonal replacement therapy. A 55-year-old woman was admitted to our Intensive Coronary Unit in February 2008 because of a communityacquired pneumonia complicated by acute heart failure. Her chief complaint was shortness of breath, which had become progressively worse during the prior 4–5 days. She had a productive yellow cough and blood-tinged sputum. Examination revealed a tachycardia (115 bpm), tachypnea 22 breaths/min, BP 90/50 mmHg, a raised venous pressure, fine bilateral basal crepitations, right-sided crackles, and dullness to percussion. She was treated conventionally in a territorial hospital for acute pulmonary edema with partial initial symptomatic recovery. The patient was also started on a ‘‘pneumonia protocol’’ with cefotaxime and azithromycin, and oxygen. Notwithstanding standard therapy for acute heart failure including nitrates, furosemide and digoxin, and the introduction of inotropic support, the patient was still hypotensive, and for this reason she was admitted to the intensive care unit of our tertiary care hospital. The past medical history revealed systemic hypertension, chronic kidney disease (GFR of 25 ml/min), subclinical hypothyroidism (TSH 6.3 lU/mL with normal FT3 and FT4), and surgical intervention for aneurysmectomy of the left middle cerebral artery, which had been performed in 2006. She never smoked or used alcohol EtOH or drugs. She lived with her family. A complete mono-two-dimensional and Doppler echocardiographic examination was performed. The ultrasound analysis displayed a very enlarged poorly contracting left ventricle (EF 13%) with moderate-to-severe mitral regurgitation (see Fig. 1; Table 1). Diastolic function was moderately impaired. Interestingly, a previous echocardiogram obtained in 2006 was reviewed, and only displayed mild LV hypertrophy with normal cavity diameters and a preserved systolic function (EF 55–60%). After resolving the decompensated HF and the right pneumonia, the patient was still in class IV of the NYHA, and could not undergo a cardiopulmonary stress test that we routinely perform in CHF patients. To rule out ischemic etiology, a coronary angiography was performed that revealed no significant coronary stenosis. An endomyocardial biopsy was suggested but not performed since the patient refused the procedure. A complete hormonal panel showed low levels of earlymorning serum cortisol and undetectable levels of serum IGF1 without evidence of secondary gonadal failure (Table 1). Thyroid failure was partial insofar as TSH increased up to 10.9 lU/mL, indicating residual pituitary secretion. We next performed a GHRH ? arginine stimulation test for diagnosis A.M. Marra and M. Arcopinto contributed equally to this work.

Do we need more than just powerful blood pressure reductions? New paradigms in end-organ protection.

Antihypertensive therapy can lower the risk of cardiovascular morbidity and mortality. Yet, partly because of inadequate dosing, wrong pharmacological choices, and poor patient adherence, hypertension control remains suboptimal in the majority of hypertensive patients. Achieving greater blood pressure control requires a multifaceted approach that raises awareness of hypertension, uses effective therapies, and improves adherence. Particular classes of antihypertensive therapy have beneficial actions beyond blood pressure and studies have evaluated differences in cardiovascular protection among classes. The LIFE and HOPE studies showed between-class differences that may be due to effects other than blood pressure-lowering. In the ONTARGET study, telmisartan and ramipril provided similar cardiovascular protection but adherence was higher with telmisartan, which was better tolerated. This difference in compliance is likely to be important for long-term therapy. The selection of an agent for cardiovascular protection should depend on an appreciation of its composite properties, including any beneficial effects on tolerability and increased patient adherence, as these are likely to be advantageous for the long-term management of hypertension. This review examines the evidence that the effects beyond blood pressure provided by some antihypertensive agents can also lower the risk of cardiovascular, cerebrovascular, and renal events in patients with hypertension.

Growth Hormone as Biomarker in Heart Failure

The impairment of growth hormone (GH)/insulin growth factor-1(IGF-1) plays a crucial role in chronic heart failure (CHF). Several studies have shown that patients affected by this condition display a more aggressive disease, with impaired functional capacity and poor outcomes. Interestingly, GH replacement therapy represents a possible future therapeutic option in CHF. In this review, the authors focus on the assessment of the main abnormalities in GH/IGF-1 axis in CHF, the underlying molecular background, and their impact on disease progression and outcomes.

Detectable interleukin-9 plasma levels are associated with impaired cardiopulmonary functional capacity and all-cause mortality in patients with chronic heart failure

Detectable interleukin-9 plasma levels are associated with impaired cardiopulmonary functional capacity and all-cause mortality in patients with chronic heart failure Alberto M. Marra , Michele Arcopinto , Andrea Salzano , Emanuele Bobbio , Salvatore Milano , Gabriella Misiano , Francesco Ferrara , Olga Vriz , Raffaele Napoli , Vincenzo Triggiani , Pasquale Perrone-Filardi , Francesco Saccà , Francesco Giallauria , Andrea M. Isidori , Carlo Vigorito , Eduardo Bossone , Antonio Cittadini c,l,⁎

Pregabalin-induced first degree atrioventricular block in a young patient treated for pain from extrapulmonary tuberculosis

Pregabalin, widely used in the treatment of several pain disorders, is usually well tolerated. Uncommonly, the drug may induce cardiac side effects, rarely prolongation of the PR interval. The latter has never been described in patients with healthy heart or normal renal function. We characterize a unique case of a young man with extrapulmonary tuberculosis and no detectable or known cardiac or kidney diseases, treated with pregabalin to control the severe pain due to the involvement of the spinal cord by the tuberculosis, showing an atrioventricular (AV) block due to pregabalin administration. The reported case emphasizes the need of monitoring PR interval during treatment with pregabalin, even in patients without background of cardiac or renal diseases.