Right ventricular performance in severe obesity. Effect of weight loss.

BACKGROUND: The effects of severe obesity on right ventricular function in the absence of associated cardiopulmonary disease are not well known. Right myocardial performance index (R-MPI) is an echocardiographic index to non-invasively assess the right ventricular function. The aim of our study was to assess R-MPI in individuals with severe but uncomplicated obesity before and after a significant weight loss induced by bariatric surgery. PATIENTS AND METHODS: Fifteen obese females (OB) without cardiovascular and pulmonary diseases were examined. In all subjects, R-MPI was calculated by Doppler echocardiography as the sum of isovolumetric contraction time and isovolumetric relaxation time divided by ejection time. Furthermore, pulmonary function test (PFT) and 6-min walking test (6mWT) were performed. Ten healthy subjects with normal weight (HS) were also evaluated as controls. R-MPI, PFT and 6mWT were also re-evaluated one year later in 12 obese subjects treated with gastric banding after a consistent weight loss (> 20%). RESULTS: A prolongation of R-MPI was found in OB before bariatric surgery in comparison to the HS (0.47 +/- 0.04 and 0.29 +/- 0.05, respectively; P < 0.001). R-MPI significantly improved in OB 12 months after surgery (0.32 +/- 0.03) and was no longer different from HS. R-MPI positively correlated to body mass index (BMI). A significant association was found between the reduction of BMI after bariatric surgery and the distance walked during the 6mWT. CONCLUSIONS: These results show a right ventricular dysfunction in severe uncomplicated obesity, associated with an impaired functional capacity which recovers after consistent weight loss.

Effect of moderate red wine intake on cardiac prognosis after recent acute myocardial infarction of subjects with Type 2 diabetes mellitus.

BACKGROUND: Oxidative stress and increased inflammation have been reported to be increased in subjects with diabetes and to be involved in the pathogenesis of cardiovascular complications after myocardial infarction (MI). It is well recognized that red wine has antioxidant and anti-inflammatory activities. We examined the effects of moderate red wine intake on echocardiographic parameters of functional cardiac outcome in addition to inflammatory cytokines and nitrotyrosine (oxidative stress marker), in subjects with diabetes after a first uncomplicated MI. METHODS: One hundred and fifteen subjects with diabetes who had sustained a first non-fatal MI were randomized to receive a moderate daily amount of red wine (intervention group) or not (control group). Echocardiographic parameters of ventricular dys-synchrony, circulating levels of nitrotyrosine, tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP) were investigated at baseline and 12 months after randomization. RESULTS: After 1 year of diet intervention, concentrations of nitrotyrosine (P < 0.01), CRP (P < 0.01), TNF-alpha (P < 0.01), IL-6 (P < 0.01) and IL-18 (P < 0.01) were increased in the control group compared with the intervention group. In addition, myocardial performance index (P < 0.02) was higher, and transmitral Doppler flow (P < 0.05), pulmonary venous flow analysis (P < 0.02) and ejection fraction (P < 0.05) were lower in the control group, indicating ventricular dys-synchrony. The concentrations of nitrotyrosine, CRP, TNF-alpha and IL-6 were related to echocardiographic parameters of ventricular dys-synchrony. CONCLUSIONS: In subjects with diabetes, red wine consumption, taken with meals, significantly reduces oxidative stress and pro-inflammatory cytokines as well as improving cardiac function after MI. Moderate red wine intake with meals may have a beneficial effect in the prevention of cardiovascular complications after MI in subjects with diabetes.

Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics.

BACKGROUND: Postprandial plasma glucose (PPG) excursion is a significant determinant of overall metabolic control as well as an increased risk for diabetic complications. Older persons with type 2 diabetes mellitus (DM2) are more likely to have moderate cognitive deficits and neurophysiologic and structural changes in brain tissue. Considering that poor metabolic control is considered a deranging factor for tissue/organ damage in diabetics, the authors hypothesized that PPG excursion is associated with a decline in cognitive functioning and that a tighter control of PPG may prevent cognitive decline. METHODS: Two groups of aged diabetic patients were randomly selected to be treated with repaglinide (n = 77) or glibenclamide (n = 79). RESULTS: Coefficient of variation of PPG (CV-PPG) was associated with Mini-Mental State Examination (MMSE) scores (r = -0.3410; p < 0.001) and a composite score of executive and attention functioning (r = -0.3744; p < 0.001) after adjusting for multiple confounders. Both groups showed a significant decline in hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG), but only the repaglinide group demonstrated a significant decline of CV-PPG over time. In models investigating the change in cognitive functioning over time, adjusted for HbA1c and CV-FPG, a decline in cognitive functioning was observed only in the glibenclamide group (p < 0.001). After adjusting for CV-PPG, the authors no longer found a decline in executive and attention functioning composite score (p = 0.085) or the MMSE (p = 0.080) with glibenclamide. CONCLUSIONS: Exaggerated postprandial glucose (PPG) excursions are associated with a derangement of both global, executive, and attention functioning. A tighter control of PPG may prevent cognitive decline in older diabetic individuals.

[Inhibitors of the platelet's receptor GPIIb/IIIA. Progress in the treatment of acute myocardial ischemia and future trends]. / Gli inibitori della GPIIb/IIIa. Progressi nella terapia dell'ischemia miocardica acuta e prospettive future.

The possible mechanisms inducing acute coronary obstruction starting from the atherosclerotic plaque are illustrated. The effects of the inhibitors of the platelet's receptor GPIIb/IIIa and the results of the main trials performed using these inhibitors are reported. Finally, the results obtained immediately before their employment in the coronary angioplasty with or without stent's implantation are also reported. The first applications in acute ischemic stroke appear to be favourable too.

What drug must be used to avoid the most common hypertensive complications?

After recalling that cardiovascular complications represent the most frequent cause of mortality and morbidity in hypertensive patients, the author describes the main mechanism responsible for increased plasma level concentrations of Angiotensin in this syndrome. He subsequently illustrates the effects of ACE-inhibitors, differentiating them from AT1-receptors. The anti-hypertensive actions of new b-blockers, like Carvedilol and Nebivolol are also explained. In addition, the anti brain hemorrhage and heart-failure effects of diuretics in hypertensive patients are briefly summarised. Finally, the anti-calcinotic effect and anti-embolic action of calcium-antagonist drugs are also underlined.

[Surgical treatment and interventional therapy in cerebral ischemia]. / Trattamento chirurgico e terapia interventistica nell'ischemia cerebrale.

The aim of this review was to evaluate the possibility of correcting cerebral ischemia (including both extracranial varieties) using elective as well as emergency surgery in order to avoid the onset of acute cerebral ischemia. The study included patients suffering from cerebral ischemia with a thromboembolic etiology. The author describe the emergency surgical procedures currently used in embolic forms affecting the extracranial vessels and percutaneous transluminal angioplasty (PTA) which is confined solely to extracranial vessels at present. In the authors' opinion, this method (with or without the application of one or more stents) will soon represent the routine method of cerebral revascularisation in the near future. The authors review the results currently obtained using extracranial PTA in the main brain surgery centres worldwide, the most frequent complications and the problems still to be resolved. In conclusion, it is useful to use interventional procedures to treat both extracranial and intracranial lesions in order to significantly reduce mortality from acute cerebral ischemia and its functional sequelae.

Prevention of left ventricular hypertrophy by ACE-inhibitor, ramipril in comparison with calcium-channel antagonist, felodipine.

This perspective study was performed to demonstrate the prevention of left ventricular hypertrophy by ACE-inhibitor, ramipril, in hypertensives of recent onset. Thirty-four hypertensive patients, treated with ramipril (group I), and 32 controls who received another frequently employed drug (the calcium channel-antagonist, felodipine (group II), were evaluated. Neither of two groups received any anti-hypertensive drug and did not suffer from left ventricular hypertrophy. All selected patients underwent M-mode echocardiography for measuring the following parameters: diastolic diameter of left ventricle, (DDLV); systolic diameter of left ventricle (SDLV); inter-ventricular septum (IVS); thickness of the posterior wall (PW); and left ventricular mass index (LVMI). Two anti-hypertensive drugs reduce systemic hypertension the same way. But, in hypertensives receiving ramipril (group I), the echocardiographic parameters of the left ventricle increased non-significantly. On the other hand, in those treated with felodipine (II group), these parameters significantly changed. The mechanisms of non-increase in cardiac and non-cardiac proteins, due to the ACE-inhibitors, are illustrated.

Pharmacological doses of vitamin E and insulin action in elderly subjects.

Twenty elderly (77 +/- 0.4 y), nonobese [body mass index (in kg/m2) 26.4 +/- 0.5] subjects with normal glucose tolerance were submitted to a euglycemic hyperinsulinemic (3.5 pmol.min/kg) glucose clamp in a double-blind, crossover, randomized procedure after 4 mo treatment with either vitamin E (900 mg d-alpha-tocopherol/d, Ephynal; Roche, Milan, Italy) or placebo. Body mass index was practically unchanged throughout the study. After the glucose clamp, insulin-mediated stimulation 2 of whole-body glucose disposal (18.4 +/- 0.5 vs 26.1 +/- 0.6 mumol.min/kg lean body mass P < 0.02) was significantly potentiated by vitamin E rather than placebo administration. Furthermore, net changes in plasma vitamin E concentrations correlated with net changes in insulin-stimulated whole-body glucose disposal (r = 0.60 P < 0.003). Plasma vitamin E concentrations seem to play an important role in the modulation of insulin action in elderly people.

Slowing of mitral valve annular calcium in systemic hypertension by nifedipine and comparisons with enalapril and atenolol.

Mitral annular calcium (MAC) is a condition that often occurs in patients with systemic hypertension. To evaluate the effectiveness of nifedipine in preventing MAC, 223 patients with systemic hypertension of recent onset and without MAC were selected and randomly enrolled in 3 groups: group 1 (76 patients) received nifedipine; group 2 (72 patients) received enalapril; and group 3 (75 patients) received atenolol. After 5 years, these treatments significantly reduced systolic (p < 0.001) and diastolic (p < 0.05) blood pressure (BP) in 3 treated groups. M-mode echocardiography revealed MAC only in 2 patients in the nifedipine group (2.6%), in 13 in the enalapril group (18%) and in 15 in the atenolol group (20%). The degree of MAC was mild (< 5 mm) in the 2 patients in group 1, in 5 of the 13 in group 2, and in 6 of the 15 in the group 3, whereas it was severe (> 5 mm) in the remaining 8 in the enalapril group and in the other 9 in the atenolol group. There was also a significant correlation in the degree of MAC, left atrial enlargement and mitral regurgitation. In addition, atrial fibrillation and atrioventricular conduction defects were associated with severe MAC. These results indicate that nifedipine is an effective drug both in the long-term management of systemic hypertension and in preventing or delaying MAC.

Comparison of nitrendipine and cilazapril in patients with hypertension and non-insulin-dependent diabetes mellitus.

The metabolic and cardiovascular effects of nitrendipine and cilazapril in patients who have elevated blood pressure and non-insulin-dependent diabetes mellitus (NIDDM) were compared. After at least 6 weeks of a washout period, 20 NIDDM patients who had diastolic blood pressure in the range of 90-105 mm Hg received a single-blind placebo for 4 weeks and then were randomized to receive 20 mg nitrendipine once daily and 5 mg cilazapril once daily each for 12 weeks according to a crossover, double-blind procedure. Nitrendipine and cilazapril reduced diastolic blood pressure levels 12% and 13%, left ventricular mass index (LVMI) levels 13% and 12%, and raised whole glucose disposal levels 18% and 19.5%, respectively. Only nitrendipine reduced glucose-stimulated insulin levels. Nitrendipine is as effective as cilazapril in lowering diastolic blood pressure and LVMI levels and in increasing glucose disposal levels in these patients.

A clinical, genetic and echocardiographic study of hypertrophic cardiomyopathy in a large family.

OBJECTIVES: To confirm recent reports on the incidence of human lymphocyte antigens (HLA) in familial hypertrophic cardiomyopathy and to better define the genetic patterns found in these patients. METHODS: A large family (31 members, 18M, 13F, age range 6-80 years) with a high incidence of hypertrophic cardiomyopathy was screened for HLA, dermatoglyphic patterns and blood subtyping. RESULTS: Our finding show variable expression of the disease and reduced penetrance. No linkage between the disease-causing gene and HLA loci could be demonstrated in the family. There was no specific haplotype which present in all affected individuals and missing in all controls. Haplotype A2 B18 was the most commonly encountered in affected individuals but was absent in IV 3 and present in a few controls. No linkage was found between the disease-responsible gene and the blood groups. Finally, no typical pattern emerged from the dermatoglyphic studies. CONCLUSION: The genetic assessment of this family, in agreement with other European studies, showed no clear correlation between hypertrophic cardiomyopathy and blood groups ABO, Rh, Lewis, Duffy and was unable to show atypical or unusual dermatoglyphic patterns.

Impaired left ventricular relaxation and hyperinsulinemia in patients with primary hypercholesterolemia.

Fifteen non-obese patients with familial hypercholesterolemia and fifteen normocholesterolemic subjects matched for age, body mass index, waist/hip ratio, arterial blood pressure and sedentary life style underwent blood sampling for determination of fasting plasma glucose, insulin, total-, LDL-, HDL-cholesterol, triglycerides, free fatty acids, apolipoprotein A1 and B. In both groups of subjects we determined erythrocyte membrane microviscosity and performed an echocardiographic study. We demonstrated that hypercholesterolemic patients had a significant increase in fasting plasma total cholesterol (8.9 +/- 0.5 vs. 5.5 +/- 0.3 mmol/l, P less than 0.001), insulin (79 +/- 4 vs. 58 +/- 4 pmol/l, P less than 0.05) and apolipoprotein B (2.2 +/- 0.5 vs. 1.3 +/- 0.5 g/l P less than 0.01). In the echocardiographic study we found a significant impairment in left ventricular relaxation (isovolumic relaxation time (IRT) 106 +/- 6 vs. 73 +/- 7 ms, P less than 0.01). Erythrocyte membrane microviscosity (0.253 +/- 0.004 vs. 0.225 +/- 0.003, P less than 0.05) was also increased in hypercholesterolemic patients. Finally we found that erythrocyte membrane microviscosity correlated with fasting plasma insulin levels (r = -0.46, P less than 0.03) and IRT (r = -0.52, P less than 0.01).

Progressive impairment of left ventricular diastolic filling with advancing age: a Doppler echocardiographic study.

OBJECTIVE: To identify the sequence and significance of left ventricular filling abnormalities associated with progressive aging in humans. DESIGN: Cross-sectional study comparing three age groups. SETTING: Department of Geriatrics at University of Naples. PARTICIPANTS: Seventy-five healthy subjects in three age groups: 25 subjects from 25 to 45 years (Group I), 25 subjects from 46 to 65 years (Group II), and 25 subjects from 66 to 85 years (Group III). INTERVENTION: None. MAIN OUTCOME MEASURES: All underwent pulsed-doppler echocardiography under color guide to measure the following parameters: peak velocity flow for early (E wave) and late (A wave) mitral flow; A/E wave ratio; deceleration time of mitral flow (MDt); isovolumic relaxation time (IRT); ratio of velocity time integrals of the A wave to the velocity time integrals of the entire mitral spectrum (VTIA/VTIM). RESULTS: Peak velocity of the E wave was slightly lower in Group II and III compared to Group I; in contrast, peak velocity of the A wave was greater (P less than 0.005) in aged individuals. Also A/E wave ratio, MDt, and IRT were significantly greater with advancing age (P less than 0.01; P less than 0.05 and P less than 0.001, respectively). Finally, VTIA/VTIM tended to be greater in the oldest group, but not significantly so. CONCLUSIONS: Left ventricular relaxation is progressively impaired in late middle age and old age, presumably an early marker of cardiac aging. Increased left atrial pressure is compromised only in the oldest group, presumably representing a compensation for impaired left ventricular relaxation.

Hemodynamic changes in left ventricular function during acute coronary insufficiency: a Doppler echocardiographic study.

To define the availability of Doppler echocardiography in evaluating left ventricular hemodynamic changes induced by some clinical findings of acute coronary insufficiency, we selected 12 patients with angina and 32 affected by acute myocardial infarction. Doppler echocardiography was performed at hospital admittance and during recovery time. Left ventricular contractility was defined on the systolic aortic flow spectrum by measuring the aortic velocity maximum, the time to peak/left ventricular ejection time ratio, and the cardiac output. During the first examination, left ventricular contractility significantly decreased in patients with angina and in those with acute myocardial infarction. After the acute phase, these parameters slightly improved. Left ventricular diastolic filling was evaluated in the transmitral flow. A decreased E-wave velocity and an increased late component (A wave) with inversion of the E/A wave ratio were found in patients with acute myocardial infarction during the first examination. This morphology inverts when the patients stabilize. On the contrary, this ratio stayed above one during and after angina. In this study, we also defined the usefulness of the color Doppler method in setting up criteria to identify some early morphological complications of acute myocardial infarction in 12 patients with acute infarction and a new systolic murmur. This technique showed an ischemic rupture of the ventricular septum in five cases and mitral regurgitation in seven. The color Doppler method has allowed us to obtain a semi-quantitative assessment of the mitral regurgitation and the location of the ventricular septal defect.

Effectiveness of glibenclamide on myocardial ischemic ventricular arrhythmias in non-insulin-dependent diabetes mellitus.

Glibenclamide, a hypoglycemic sulfonylurea, is a blocker of the adenosine triphosphatase-modulated potassium ion channels. The opening of these channels in the myocardial cells, induced by acute myocardial hypoxia, can be responsible for ischemic ventricular arrhythmias. To evaluate the antiarrhythmic effects of this drug 19 non-insulin-dependent diabetic patients were selected. They had coronary artery disease and evidence on Holter monitoring of ventricular premature complexes or nonsustained ventricular tachycardia, or both, induced by transient myocardial ischemia. In all patients, 24-hour electrocardiographic monitoring was performed to evaluate the number and duration of myocardial ischemic events, the frequency of ventricular premature complexes and nonsustained ventricular tachycardia per minute of ischemia and the percentage of ventricular premature complexes versus total ischemic beats. Selected patients were classified in 2 groups: group A (9 patients) received metformin (placebo) and group B (10 patients) was treated with glibenclamide. On the fourteenth day patients underwent 24-hour control monitoring. Then a crossover between the 2 groups was made and a new Holter monitoring sequence was performed at the end of the second phase. Results indicate that glibenclamide significantly (p less than 0.001) reduced both the frequency of ventricular premature complexes and the episodes of nonsustained ventricular tachycardia during transient myocardial ischemia, but did not change the number and duration of acute myocardial ischemic attacks and did not reduce the spontaneous ventricular arrhythmias. Thus, glibenclamide appears to have an antiarrhythmic effect in preventing ventricular arrhythmias induced by transient myocardial ischemia.

The long-term efficacy of ibopamine in treating patients with severe heart failure: a multicenter investigation.

This randomized, double-blind, placebo-controlled, multicenter trial compared the effects of treatment with ibopamine with those of placebo in patients with severe heart failure who still showed symptoms although they were receiving standard therapy with digitalis and diuretics. The results showed a significant and sustained improvement in exercise tolerance (+70% about in average), clinical condition, and NYHA functional class and a decrease in cardiothoracic ratio and left ventricular end-systolic wall stress in patients treated with ibopamine, digitalis, and diuretics (group 1) compared with patients treated with digitalis, diuretics, and placebo (group 2).

Hypertension in the elderly is associated with impaired glucose metabolism independently of obesity and glucose intolerance.

We evaluated insulin secretion, insulin sensitivity and blood pressure changes after oral administration of glucose in hypertensive and normotensive elderly subjects. The hypertensive group consisted of 12 subjects (aged 72.5 +/- 1.9 years, mean +/- s.e.m.) who had a history of hypertension lasting 10-25 years and were not more than 20% above ideal body weight. The normotensive group consisted of 12 subjects matched to the hypertensive group for age, sex and weight. All subjects underwent an oral glucose tolerance test (75 g glucose dissolved in 300 ml water), an intravenous glucose tolerance test (0.33 g/kg of a 50% glucose solution) and a euglycaemic, moderately hyperinsulinaemic glucose clamp. In both groups, oral glucose tolerance was normal according to the criteria of the National Diabetes Data Group; the hypertensive group showed significantly higher plasma glucose and insulin responses to oral glucose than the normotensive group, suggesting insulin resistance. The results of the euglycaemic clamp confirmed the state of reduced insulin sensitivity. Our data demonstrate that oral but not intravenous glucose produces a fall in blood pressure in hypertensive but not in normotensive patients, probably because activation of the sympathetic nervous system is impaired in hypertensive subjects; moreover, hypertension in the elderly seems associated with a state of reduced sensitivity to insulin.

Effects of the angiotensin converting enzyme inhibitor enalapril compared with diuretic therapy in elderly hypertensive patients.

The aim of this study was to evaluate the usefulness of the angiotensin converting enzyme (ACE) inhibitor enalapril in a group of 30 patients (mean age 73.3 years) with moderate hypertension and normal haematological and chemical parameters (170 +/- 8.1 mmHg systolic and 104 +/- 5.8 mmHg diastolic blood pressure), who were receiving diuretic therapy with chlorthalidone (12.5 mg/day). This therapy caused a significant decrease in systolic and diastolic blood pressure (to 165 +/- 6.7 and 98 +/- 4.7 mmHg, respectively; P less than 0.001) but it also induced hypokalaemia (3.04 +/- 0.7 mmol/l; P less than 0.001) and multiple (greater than 10/h) and complex premature ventricular depolarizations (2nd, 3rd and 4th Lown grade). Enalapril treatment (5 mg/day for 5 days and 10 mg thereafter) was added to the diuretic therapy and after 2 months a further decrease in blood pressure was observed (to 158 +/- 5.6 mmHg systolic, P less than 0.001; 87.2 +/- 5.0 mmHg diastolic, P less than 0.001). Moreover, there was a significant reduction in the mean heart rate (from 79 to 72 beats/min, P less than 0.005) and an increase in serum potassium (to 4.19 +/- 0.2 mmol/l; P less than 0.001). In 80% of patients a 24-h dynamic electrocardiogram showed a significant reduction in both the number and complexity of premature ventricular depolarizations. Our findings suggest that ACE inhibitors can be useful in patients developing hypokalaemia during therapy. However, we are not yet able to explain the beneficial effects of enalapril in decreasing the frequency of premature ventricular depolarizations.