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Deborah Cosmi - Top 30 Publications

Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes.

Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes.

Trials of Patent Foramen Ovale Closure.

Declining Risk of Sudden Death in Heart Failure.

Large Left Ventricular Aneurysm and Multifocal Myocardial Involvement in a Patient With Systemic Sclerosis.

A 43-year-old man with systemic sclerosis and chest pain had negative T waves in precordial electrocardiographic leads. The echocardiogram showed a large left ventricular apical accessory chamber. The coronary arteries were normal. Cardiac magnetic resonance imaging (MRI) showed a large fibrotic aneurysm and a small patch of midwall late enhancement in the septum. The aneurysm was surgically removed. At the 8-month follow-up, cardiac MRI showed the appearance of a new nodular lesion in the anterior wall, causing a localized wall motion abnormality. Myocardial involvement in patients with systemic sclerosis can be severe, and cardiac MRI evaluation is fundamental.

Digitalis, a drug to be scrapped?

We performed a comprehensive review of the scientific literature on the use of digoxin in heart failure and atrial fibrillation. In congestive heart failure (CHF) there is only one randomized trial with a statistical sample sufficiently large. In this trial (DIG trial), which enrolled patients with systolic left ventricular dysfunction in sinus rhythm, digoxin had a neutral action on mortality and modestly reduced the overall need of hospitalization. The study was conducted in the pre-beta-blocker era and, therefore, it has a doubtful application to the current clinical context. There are no randomized trials on atrial fibrillation, either with or without heart failure. Several observational and retrospective studies and meta-analysis have shown an association between the use of digoxin and increased mortality about 20%. Both in the European and American guidelines, even in class I recommendations, evidence is not supported by randomized or observational trials, but just by experts' opinions. Digoxin use in CHF and atrial fibrillation is related to the physician's clinical judgment, based more on consolidated custom that on established scientific evidence. In our opinion, this therapy should be withdrawn until new randomized controlled trials will provide evidence of its efficacy. Two trials have been planned to this aim. Also the issue of toxicity threshold is still unresolved; digoxinemia values should be <1 ng/ml if digoxin is used, to avoid overdosing and toxicity with increased mortality.

Giant left ventricular pseudoaneurysm in a scleroderma patient: evaluation by cardiac magnetic resonance.

Regular wine consumption in chronic heart failure: impact on outcomes, quality of life, and circulating biomarkers.

Moderate, regular alcohol consumption is generally associated with a lower risk of cardiovascular events but data in patients with chronic heart failure are scarce. We evaluated the relations between wine consumption, health status, circulating biomarkers, and clinical outcomes in a large Italian population of patients with chronic heart failure enrolled in a multicenter clinical trial.

Progression of Fabry cardiomyopathy despite enzyme replacement therapy.

Metformin and insulin in chronic heart failure: contraindications not contraindicated and indications not indicated.

Glucose-lowering treatment in patients with type 2 diabetes and heart failure is controversial. Metformin is clearly contraindicated when such diseases coexist. Conversely, no contraindications have been established for insulin in this subset of patients, even though several observational and retrospective studies have shown increased mortality and worsening heart failure. Data from the literature have demonstrated that in this patient population, which accounts for one third of all cases of heart failure, metformin reduces mortality by 14-35%. In patients with a glomerular filtration rate >30 ml/min who do not show dehydration, shock, sepsis, severe liver disease or hypoxemia, the administration of metformin doses <2 g/day was associated with a null risk of lactic acidosis. The positive effects of metformin are correlated with the reduction in insulin resistance, which is responsible for both the onset and development of heart failure in diabetic patients. Insulin can provoke severe hypoglycemia and fluid retention, resulting in negative effects. Further randomized and prospective studies are warranted to address these controversial issues in such a large population with high mortality and morbidity rates. Longitudinal studies would be crucial to the understanding of the optimal therapy and for stratification of patients according to the severity of heart failure.

Hypoglycemic therapy in heart disease patients with type 2 diabetes mellitus.

In type 1 diabetes, insulin treatment reduces complications related to microvascular disease and atherosclerosis. The same holds true in patients with short duration of type 2 diabetes, treated either with oral antidiabetic drugs or with insulin. Conversely, in patients with long-standing type 2 diabetes, advanced age or history of cardiovascular disease, treatment with oral diabetic drugs or insulin must be given with caution because of the unfavorable risk-benefit profile when these drugs are used with too aggressive aims. In the last year, several studies have clearly demonstrated that an excessive reduction of glycated hemoglobin exposes the patient at risk of hypoglycemia and fattening, with neutral results about clinical events or even with a paradoxical increase of cardiovascular events (hospitalization and mortality). The glycemic goal in heart disease and diabetic patients should be settled on higher values (probably 7-8%). There are no significant differences among drugs that reduce insulin resistance and drugs that stimulate its secretion. The only drug that proved to be effective in reducing cardiovascular events is metformin, which increases AMP-activated protein kinase activity and has a potent cardioprotective effect against ischemia-reperfusion injury. These findings should be confirmed in larger longitudinal studies in heart disease patients. Patients in intensive care units should be treated with intravenous insulin with a glycemic target <180 mg/dl (mean 142 mg/dl) because more aggressive goals may lead to increased mortality. These results demand important considerations about the management of heart disease patients with type 2 diabetes, also because self-monitoring of blood glucose concentration seems to induce an increase in depression. Conversely, an aggressive multifactorial intervention (improvement of lifestyle, blood pressure and dyslipidemia control, platelet aggregation inhibitors in secondary prevention) reduces effectively cardiovascular events and mortality.

Insulin therapy may hasten congestive heart failure in cardiac patients: case series and review of the literature.

We describe the appearance, within a few weeks from the beginning of insulin therapy, of signs and symptoms of congestive heart failure in three diabetic patients with known cardiac disease (one with aortic stenosis, one with hypertensive heart disease and one with ischemic heart disease), who however had never previously shown signs of heart failure. Reduction of the dose of insulin, along with a moderate diuretic therapy, led to resolution of clinical condition. Sodium retention and increased vascular permeability by insulin could be the causes of this phenomenon. In clinical practice it is necessary to remember that the beginning of insulin treatment could exacerbate left ventricular dysfunction to an overt heart failure. Future studies should evaluate whether insulin therapy plays a negative role in the long-term prognosis of patients with asymptomatic left ventricular dysfunction, as it has already been hypothesized in those with overt heart failure.

Obstructive sleep apnea syndrome and cardiovascular diseases.

Obstructive sleep apnea (OSA) syndrome is one of the most common respiratory disorders in humans. There is emerging evidence linking OSA to vascular disease, particularly hypertension. The underlying pathophysiological mechanisms that link OSA to cardiovascular diseases such as hypertension, congestive heart failure and atrial fibrillation are not entirely understood, although they certainly include mechanical events, increased sympathetic activity and oxidative stress. This review will examine the evidence and mechanisms linking OSA syndrome to cardiovascular disease.