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There has been an exponential increase in incidence of severe aortic stenosis partially due to the lengthening of average lifespan. Among the most disabling symptoms of aortic stenosis are chest pain, fatigue, and dyspnea up to heart failure and pulmonary edema. In some cases, to worsen this symptomatology, there are coagulation disorders linked to an alteration of functional von Willebrand factor, responsible for progressive anemia. In elderly patients with severe aortic stenosis, the simultaneous presence of an angiodysplasia of the colon can favor blood dripping, which may cause iron deficiency anemia. The coexistence of colonic angiodysplasia and acquired von Willebrand disease in patients with aortic stenosis was identified as Heyde's syndrome. In the long term, Heyde's syndrome can contribute to worsen the clinical manifestations of severe aortic stenosis leading to heart failure. Here, we describe the case of a patient suffering of severe calcific aortic stenosis who developed Heyde's syndrome achieving a condition of heart failure with mildly reduced ejection fraction. LEARNING OBJECTIVES: Severe aortic stenosis can alter the conformation of the circulating von Willebrand glycoprotein, causing an alteration of the hemostatic balance. When angiodysplasia of the colon coexists with aortic stenosis, a gastrointestinal blood drip can occur inducing an iron deficiency anemia that worsens the symptoms of aortic valvulopathy. This condition often remains undiagnosed. We discuss the pathophysiologic and hemodynamic mechanisms responsible for acquired von Willebrand syndrome in patients with severe aortic stenosis focusing on the clinical elements useful to raise the diagnostic suspicion and analyzing different alternative tools to recognize it promptly.

BACKGROUND: In Type 2 diabetic patients, clinical diagnosis of diabetic nephropathy (DN) is generally based on the concomitant presence of abnormal albuminuria and severe retinopathy. In this high-risk population, cardiovascular (CV) outcome has never been evaluated. METHODS: A cohort of 742 Type 2 diabetic patients with DN from 17 national centres was selected by the presence of persistent albuminuria ≥ 30 mg/day and severe diabetic retinopathy and was followed prospectively. Time to CV event (CV death, non-fatal myocardial infarction, non-fatal stroke, revascularization, major amputation) was the primary composite end point and it was analysed by multivariable Cox's proportional hazards model. The interaction between albuminuria and glomerular filtration rate (GFR) was specifically investigated. RESULTS: Median follow-up was 4.6 years. Overall 242 events (26% of which fatal) were observed in 202 patients. The proportion of CV events increased from 19 to 40% as GFR declined from the highest (≥ 90 mL/min/1.73 m(2)) to the lowest (

Objective: Non-invasive testing often does not identify coronary artery disease (CAD) in diabetic subjects. This study was designed in order to examine the prevalence of CAD in a cohort of asymptomatic type 2 diabetic patients at high cardiovascular risk and negative nuclear imaging, using multi-slice computed tomography (MSCT) angiography. Methods: In total, 770 type 2 diabetic patients were screened from January 2008 through July 2010. Of these, 132 Caucasians with diabetic nephropathy and asymptomatic for angina were eligible for a cross-sectional study. Patients underwent MSCT after ischaemia was excluded by myocardial Single Photon Emission Computed Tomography (SPECT) at rest and after dynamic exercise. When obstructive plaques were found (≥50% lumen narrowing), patients were sent to conventional coronary angiography (CCA). Results: Six subjects were not included in the analysis because of motion artefacts. MSCT was positive for CAD in 114 patients (90%). Within patients with positive MSCT, 60 (48% of all) showed one or more obstructive plaques. CCA confirmed significant stenosis (≥50%) in 48 of these 60 patients (80%). Some 21 (35%) showed stenosis ≥75% and were submitted to the revascularisation procedure. Conclusion: MSCT seems to better identify CAD than myocardial SPECT in asymptomatic patients with type 2 diabetes and diabetic nephropathy.

Despite the growing of pharmacological options for the treatment of diabetes, epidemiological studies suggest that a substantial proportion of patients does not achieve glycemic goals and so suffers from the risk of chronic complications. This review explores the inhibition of renal glucose reabsorption as a novel approach to treat hyperglycemia. Sodium-glucose cotransporter 2 (SGLT2), a low-affinity high-capacity transporter located in the brush-border membrane of the early segment (S1) of the proximal renal tubule, accounts for about 90% of the reabsorption of glucose from tubular fluid. Competitive inhibitors of SGLT2 that are responsible for renal excretion of glucose provide a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes. They act independently of insulin secretion, thereby minimizing the risk of hypoglycemia and weight gain, to control energy balance in a negative direction, a distinctive advantage of this class of drugs over existing oral hypoglycemic agents. Although this group of medications is still under investigation, it appears to be safe and generally well tolerated and it would be expected to improve the treatment of type 2 diabetes as monotherapy or in combination with other oral or parenteral agents. Dapagliflozin is the first agent within this class, which induces clinically meaningful reductions in FPG, PPG, HbA1c, and body weight in type 2 diabetes.

OBJECTIVES The aim of the present study was to evaluate the expression and the activity of vascular endothelial growth factor (VEGF) in the hearts of diabetic patients with chronic coronary heart disease (CHD). BACKGROUND Diabetes is characterized by a decreased collateral vessel formation in response to coronary ischemic events, although the role of VEGF in human diabetic macroangiopathy has not been fully investigated. METHODS Biopsies of left ventricular (LV) myocardium were obtained from 10 patients with type 2 diabetes and 10 non-diabetic patients with chronic CHD, all undergoing surgical coronary revascularization. Right ventricle myocardial samples taken from normal hearts were used as control specimens. Vascular endothelial growth factor and VEGF-receptors (flt-1 and flk-1) were evaluated by Western blot, reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time RT-PCR. Akt and endothelial nitric oxide synthase (eNOS) protein expression and their phosphorylated forms were also evaluated by Western blot. RESULTS Vascular endothelial growth factor, flt-1, and flk-1 messenger ribonucleic acid (mRNA) and protein expressions were increased in non-diabetic patients with CHD compared with control subjects. Remarkably, in diabetic patients, VEGF mRNA and protein levels were significantly higher, whereas flt-1, flk-1 mRNA, and protein were lower when compared with nondiabetic patients. Interestingly, phospho–flk-1 was reduced in diabetic patients compared with non-diabetic patients. As a consequence, Akt phosphorylation, eNOS protein and its phosphorylated form were significantly higher in the samples from non-diabetic patients compared with diabetic patients. CONCLUSIONS Chronic CHD in diabetic patients is characterized by an increased VEGF myocardial expression and a decreased expression of its receptors along with a down-regulation of its signal transduction. The latter could be partially responsible for the reduced neoangiogenesis in diabetic patients with ischemic cardiomyopathy

The relationship between coronary artery disease (CAD) and diabetes is widely documented [1–3], and diabetic patients present a worse CV outcome in respect to nondiabetic patients [4]. Recently, the physiopathology of CV risk in patients affected by undiagnosed or newly detected diabetes is matter of great interest [5, 6]. Actually, the prevalence of diabetes in CAD patients is not clearly estimated because diagnosis is generally based on not exhaustive criteria, such as history of diabetes or hyperglycemia during acute events. We aimed to evaluate the true prevalence of diabetes in nonacute patients affected by CAD, as assessed by coronary angiography. Six hundred and seventy nine patients admitted from November 2008 to November 2009 in the Cardiology Ward of University of Naples to perform angiography for suspect CAD were assessed for eligibility. Patients with coronary acute events in the last 4 week and subjects without angiographically detectable CAD were excluded. Moreover, treatment with steroids, acute infections, fever, or any condition that could impair glycemic metabolism were further exclusion criteria. Finally, 510 Caucasian patients (301M, 209F; age 57 ± 13 years) were eligible. Ninety seven (19%) had known diabetes (history and/or use of antidiabetic agents or newly discovered by fasting glucose value C126 mg/dl). The other 413 were submitted to standardized oral glucose test tolerance (OGTT), repeated twice in case of abnormal response [7]. Diabetes was revealed in 151 subjects, while 72 were affected by prediabetes, a condition at high risk to develop overt diabetes. Thus, the overall prevalence of diabetes was 48.6%, and the prevalence of glycemic impairments (diabetes plus prediabetes) was 62.7%. Only 190 (37.2%) showed a normal glucose tolerance (Fig. 1). The number of vessels with obstructive plaque (C50% lumen narrowing) was higher in diabetic than in nondiabetic group (1.12 ± 1.13 vs. 1.68 ± 1.33; P \ 0.01)

Diabetic cardiomyopathy is a ventricular dysfunction in the absence of coronary artery disease, valvular or hypertensive heart disease. The mechanisms underlying diabetic cardiomyopathy may involve metabolic disturbances, myocardial fibrosis, small vessel disease, microcirculation abnormalities, cardiac autonomic neuropathy and insulin resistance. Diagnostic problems emerge because no specific disease pattern characterizes the disease and because there may be coexistence in diabetes of coronary artery disease and hypertension as independent but compounding causes of biochemical, anatomical and functional alterations impairing cardiac function. In this paper we will review the role of nuclear imaging today, concentrating on the diagnostic capabilities of radionuclide ventriculography, to study the effect of insulin resistance and, more extensively, gated-single photon emission computed tomography with Tc-99m labelled agents. A broad analysis will be dedicated to: 1) positron emission tomography using perfusion agents, with the potential to quantify resting and stress blood flow and coronary flow reserve; 2) radionuclide procedures evaluating aerobic and anaerobic cardiac metabolism; and 3) cardiac neurotransmission imaging, studying the autonomic neuropathy.

OBJECTIVE—The purpose of this study was to assess the prevalence of cardiorenal risk factors, their management in a routine clinical setting, and the actual achievement of international guideline targets in a large cohort of type 2 diabetic patients with diabetic nephropathy. RESEARCH DESIGN AND METHODS—A multicentric cross-sectional study was performed in the Campania region in Italy to evaluate cardiorenal risk factors and their management in light of international guidelines. Overall, 28,550 diabetic patients were screened in the 21 participating centers; 847 (348 male and 449 female) patients with type 2 diabetes and a clinical diagnosis of diabetic nephropathy were recruited. RESULTS—Of these subjects, 749 had microalbuminuria and 98 had macroalbuminuria. Targets for blood pressure, HbA1c, LDL cholesterol, HDL cholesterol, and triglycerides were reached in, respectively, 17.5, 32.3, 30.7, 47, and 55.2% of the patients. Chronic renal failure (glomerular filtration rate CONCLUSIONS—This is the first study to investigate a large cohort of type 2 diabetic patients with early and moderate diabetic nephropathy strictu sensu. Notably, impaired renal function can be often diagnosed in these patients even in the presence of microalbuminuria. Thus, clinical diagnosis of diabetic nephopathy allows us to identify a group of patients at very high cardiorenal risk, for whom care is really difficult. We suggest that a correct diagnosis of diabetic nephropathy should always be made and that sodium intake and anemia should be routinely evaluated in these patients.

Aims We designed this study in order to determine the effect of insulin on cardiac function in overweight and obese subjects during exercise. Methods and results The cardiac function of 62 normal glucose tolerant subjects, aged 30–40 and divided into normal weight (group 1, n ¼ 22, BMI 20–24.9 kg/m 2 ), overweight (group 2, n ¼ 20, BMI 25–29.9 kg/m 2 ), and obesity (group 3, n ¼ 20, BMI 30–35 kg/m 2 ) was evaluated at rest and during dynamic exercise through angiocardioscintigraphy, when on hyperinsulinaemic euglycaemic clamp (test A) and when on normal saline infusion (test B). Left ventricular function at rest was statistically greater (P , 0.05) in both tests in overweight and obese subjects compared with normal weight controls, with no statistical difference (P ¼ 0.057) within groups between insulin and normal saline infusion. During exercise, cardiac function improved in all the subjects in both tests. The increase was lower in overweight and obese patients, even if statistically significant only in obese vs. control subjects in both tests (P , 0.05). Insulin sensitivity showed a significant correlation (P � 0.001) with left ventricular ejection fraction (LVEF) at rest and with change in LVEF during clamp. Conclusion Our findings suggest a metabolic pathogenesis for the impaired LV function in obesity.

ContextSeveral investigations as well as prospective studies have shown a significant correlation between glucose metabolism and atherosclerosis in patients without diabetes, but differences in parameters of glucose metabolism among the various degrees of coronary disease in such patients have not been specifically evaluated.ObjectiveTo investigate glucose metabolism in patients with normal glucose tolerance (NGT) and coronary heart disease (CHD).Design, Setting, and ParticipantsCross-sectional study of 234 men (mean [SD] age, 56.2 [6.1] years) with NGT and suspected CHD who were admitted from January 1 through June 30, 2001, to an academic medical center in Italy for coronary angiography.Main Outcome MeasuresCorrelation of glucose metabolic factors and extent of atherosclerosis determined by coronary angiography. Factors included levels of fasting and postload glucose and insulin, glycosylated hemoglobin (HbA1c), and lipids, as well as insulin resistance measured by homeostasis model assessment (HOMA-IR).ResultsPatients were divided into 4 groups based on coronary angiography: no significant stenosis (n = 42), 1-vessel disease (n = 72), 2-vessel disease (n = 64), and 3-vessel disease (n = 56). Simple correlation analysis showed that the factors correlated with the extent of atherosclerosis were levels of postload glucose (r = 0.667), HbA1c (r = 0.561), postload insulin (r = 0.221), and fasting insulin (r = 0.297), as well as HOMA-IR (r = 0.278) (P