Chromogranin A in heart failure; a novel neurohumoral factor and a predictor for mortality.

Background: In chronic heart failure, several hormonal systems are activated with diagnostic and prognostic implications. We tested the hypotheses that serum Chromogranin-A (CgA) -- a 49 kDa acid protein present in the secretor granules of neuroendocrine cells -- is increased in chronic heart failure and that CgA levels are a predictive factor for mortality.

Method And Results: In 160 patients with chronic heart failure, we measured serum CgA and other neuroendocrine hormones.

[Potential cost reductions for the National Health Service through a telecardiology service dedicated to general practice physicians].

Background: Rising health care costs resulted in increasing pressure on the health care system and stimulated new strategies for improving the efficiency of care. A telecardiology service provides a useful support to general practitioners in the management of cardiac patients and contributes to the optimization of health care costs in terms of appropriateness of hospital admission and diagnostic testing. The aim of our study was to evaluate the reduction in the number of referrals to the Emergency Department and to cardiological evaluation resulting from the employment of a telecardiology service by general practitioners.

Acquired growth hormone resistance in patients with chronic heart failure: implications for therapy with growth hormone.

Objectives: We aimed to determine whether growth hormone (GH) resistance is present in patients with chronic heart failure (CHF) and whether it may be linked to the biochemical response to GH treatment.

Background: Acquired GH resistance is a feature of severe illness, in particular, cachexia. In patients with CHF, the response to GH therapy appears to be variable.

Retrovirus-mediated gene transfer and galactocerebrosidase uptake into twitcher glial cells results in appropriate localization and phenotype correction.

Galactocerebrosidase (GALC) is deficient in all tissues from human patients and animal models with globoid cell leukodystrophy (GLD) or Krabbe disease. The deficiency results in decreased lysosomal catabolism of certain galactolipids including galactosylceramide and psychosine that are synthesized maximally during myelination. According to current theories, the accumulation of psychosine in humans and animals with GLD induces oligodendrocyte degeneration and myelination ceases.

Role of growth hormone in chronic heart failure: therapeutic implications.

Chronic heart failure is a multi-etiological cardiovascular disorder with high prevalence and poor prognosis. Medical treatment of dilated cardiomyopathy is aimed at alleviating heart failure symptoms. Diuretics, angiotensin-converting enzyme (ACE) inhibitors and very recently, beta-blockers have been shown to have favorable effects on symptoms, exercise capacity and mortality.

Role of growth hormone in chronic heart failure. Therapeutic implications.

Congestive heart failure is a multiple aetiology, high prevalence, poor prognosis cardiovascular disorder. Medical treatment of dilated cardiomyopathy is aimed at alleviating the symptoms of heart failure. Diuretics, ACE inhibitors and very recently, beta-blockers have been shown to have favourable effects on symptoms, exercise capacity and mortality.

Apoptosis in the skeletal muscle of patients with heart failure: investigation of clinical and biochemical changes.

Objective: To investigate the contribution of apoptosis in the development of the skeletal myopathy in chronic heart failure.

Design: The electrophoretic pattern of myosin heavy chains (MHC), fibre cross sectional area, number of in situ nick end labelling (TUNEL) positive apoptotic myocyte nuclei, and the tissue levels of caspase-3, Bcl-2, and ubiquitin were determined in biopsies taken from the vastus lateralis muscle. The study involved nine patients with severe chronic heart failure caused by ischaemic heart disease and hibernating myocardium and five controls.

Effects of oxygen on autonomic nervous system dysfunction in patients with chronic obstructive pulmonary disease.

Chronic hypoxaemia can play a pathological role in abnormalities of the autonomic nervous system (ANS). In patients with chronic obstructive pulmonary disease (COPD), chronic hypoxaemia is associated with increased mortality and only long-term oxygen therapy is able to improve their survival. Normoxaemic COPD patients have been shown to suffer from abnormalities in ANS function.

Endogenous nitric oxide in patients with chronic heart failure (CHF): relation to functional impairment and nitrate-containing therapies.

We assessed the levels of exhaled nitric oxide (eNO) in patients with chronic heart failure (CHF) according to the functional impairment and the use of nitrate-containing agents. Forty patients (age 55+/-9 years) were classified according to the NYHA classes I-II (n=18, group 1) and classes III-IV (n=22, group 2), and to the use of nitrate-containing drugs (Nitrate+, Nitrate-). Twenty-two healthy age-related subjects served as controls (group 3).

Serum from patients with severe heart failure downregulates eNOS and is proapoptotic: role of tumor necrosis factor-alpha.

Background: Cytokine activation and endothelial dysfunction are typical phenomena of congestive heart failure (CHF). We tested the hypothesis that incubating human umbilical vein endothelial cells with serum from patients with CHF will downregulate endothelial constitutive nitric oxide synthase (eNOS) and induce apoptosis.

Methods And Results: We studied 21 patients with severe CHF.

Induction of functional inducible nitric oxide synthase in monocytes of patients with congestive heart failure. Link with tumour necrosis factor-alpha.

Aims: We studied the induction of monocytic inducible nitric oxide synthase expression and the tumour necrosis factor-alpha system in patients with congestive heart failure.

Methods And Results: Forty-three congestive heart failure patients and 15 healthy subjects were studied. Antigenic tumour necrosis factor-alpha and its soluble receptors, measured by ELISA, were increased in chronic heart failure and the increase was related to the clinical severity of the syndrome (tumour necrosis factor-alpha from 8.

Endocrine predictors of acute hemodynamic effects of growth hormone in congestive heart failure.

Background: The aim of our study was to assess whether there could be any clinical and/or endocrine (spontaneous growth hormone [GH] secretion rate, baseline insulin-like growth factor-1 [IGF-1]) predictors and/or determinants of the acute effects of continuous intravenous infusion of recombinant human GH on hemodynamic parameters in 12 patients with dilated cardiomyopathy and congestive heart failure (CHF).

Methods And Results: The study involved 12 male patients with chronic CHF (ischemic in 8 patients and idiopathic in 4). Ten patients were in New York Heart Association functional class III or IV and 2 in class II.

Transduction of cultured oligodendrocytes from normal and twitcher mice by a retroviral vector containing human galactocerebrosidase (GALC) cDNA.

Krabbe disease or globoid cell leukodystropy is a lysosomal disorder caused by a deficiency of galactocerebrosidase (GALC) activity. This results in defects in myelin that lead to severe symptoms and early death in most human patients and animals with this disease. With the cloning of the GALC gene and the availability of the mouse model, called twitcher, it was important to evaluate the effects of providing GALC via a retroviral vector to oligodendrocytes in culture.

Is heart rate variability a reliable method to assess autonomic modulation in left ventricular dysfunction and heart failure? Assessment of autonomic modulation with heart rate variability.

Autonomic dysfunction seems to be involved in the progression and prognosis of congestive heart failure. Measurement of heart rate variability (HRV) provides a noninvasive method to obtain reliable and reproducible information on autonomic modulation of heart rate, but there is a difficulty in using HRV as a quantitative estimate of autonomic dysfunction in heart failure. This study was aimed at testing the hypothesis that abnormal modulation of heart rate assessed by power spectrum analysis may be present also in asymptomatic patients with left ventricular dysfunction and progress in patients with overt symptoms of congestive heart failure.

Improved exercise tolerance after losartan and enalapril in heart failure: correlation with changes in skeletal muscle myosin heavy chain composition.

Background: In congestive heart failure, fatigue-resistant, oxidative, slow type I fibers are decreased in leg skeletal muscle, contributing to exercise capacity (EC) limitation. The mechanisms by which ACE inhibitors and AII antagonists improve EC is still unclear. We tested the hypothesis that improvement in EC is related to changes in skeletal muscle composition toward type I fibers.

Tumour necrosis factor alpha as a predictor of impaired peak leg blood flow in patients with chronic heart failure.

Tumour necrosis factor alpha (TNF alpha) is increased in patients with cardiac cachexia, a condition associated with reduced peripheral blood flow both at rest and after interventions causing vasodilation. By contrast, in patients with chronic heart failure (CHF), higher TNF levels are associated with a greater capacity for vasodilation in the arm. To clarify the relationship between peripheral blood flow and TNF in CHF, we studied the relation between TNF alpha and blood flow in the leg (plethysmography, post maximal exercise and 5 min ischaemia) in 34 patients (age 63 +/- 2 years, ejection fraction 29 +/- 3%, peak VO2 16.

Left ventricular pressure-volume relationships before and after cardiomyoplasty in patients with heart failure.

Background: The aim of this study was to elucidate whether beneficial effects of cardiomyoplasty (CMP) in patients with dilated cardiomyopathy are the result of a decrease in existing ventricular dilatation or a prevention of further dilatation.

Methods And Results: Combined micromanometer-conductance catheters were used to evaluate left ventricular pressure-volume relationships in six patients with dilated cardiomyopathy before and at 6 and 12 months after CMP. Acute changes in preload and afterload were induced by a standardized leg-tilting intervention and a bolus infusion of nitroglycerin.

Augmented peripheral chemosensitivity as a potential input to baroreflex impairment and autonomic imbalance in chronic heart failure.

Background: The precise mechanisms responsible for the sympathetic overactivity and blunted baroreflex control in chronic heart failure (CHF) remain obscure. Augmented peripheral chemosensitivity has recently been demonstrated in CHF. We evaluated the relation between peripheral chemoreflex sensitivity and autonomic activity in patients with CHF.

Cardiomyoplasty as an isolated procedure to treat refractory heart failure.

Objective: Cardiomyoplasty represents a controversial therapy for chronic heart failure. The aim of this study is to review our experience of such a surgical procedure as an isolate approach to treat refractory left ventricular dysfunction.

Methods: Twenty-two patients were considered candidates for cardiomyoplasty because of chronic heart failure.

The increased ventilatory response to exercise in chronic heart failure: relation to pulmonary pathology.

Objective: To assess the exercise limitation of patients with chronic heart failure (CHF) and its relation to possible pulmonary and ventilatory abnormalities.

Setting: A tertiary referral centre for cardiology.

Methods: The metabolic gas exchange responses to maximum incremental treadmill exercise were assessed in 55 patients with CHF (mean (SD) age 57.

The influence of muscle mass, strength, fatigability and blood flow on exercise capacity in cachectic and non-cachectic patients with chronic heart failure.

Background: The influence of age, skeletal muscle function and peripheral blood flow on exercise capacity in chronic heart failure patients is controversial, possibly due to variations in skeletal muscle atrophy.

Methods And Results: To assess predictors of exercise capacity in patients with clinical cardiac cachexia, we studied 16 cachectic and 39 non-cachectic male chronic heart failure patients of similar age and ejection fraction. All cachectic patients were wasted (% ideal body weight: 81.

Chemoreceptor dependence of very low frequency rhythms in advanced chronic heart failure.

Factors responsible for very low frequency oscillations (VLF; cycle > 30 s) in the cardiovascular system remain obscure. We tested the hypothesis that increased peripheral chemosensitivity is important in the pathogenesis of VLF oscillations in patients with chronic heart failure (CHF). Fourteen male patients with stable, moderate to severe CHF (age 60 +/- 1.

Plasma hormone levels and haemodynamics in patients with chronic obstructive lung disease.

Chronic obstructive pulmonary disease (COPD) is associated with right heart failure and salt and water retention. The possible roles of haemodynamically active hormones in the early stages of COPD have not previously been described. Adrenaline, noradrenaline, renin activity, aldosterone, vasopressin, cortisol, growth hormone, prolactin and atrial natriuretic peptide (ANP) were measured during right heart catheterization in mixed venous blood and in a peripheral artery, in the supine and standing position, in two groups of patients with COPD: Group A with arterial oxygen tension (Pa,O2) < 8.