Alberto Margonato

Erectile Dysfunction Prevalence, Time of Onset and Association with Risk Factors in 300 Consecutive Patients with Acute Chest Pain and Angiographically Documented Coronary Artery Disease

OBJECTIVES The aim of this study was to assess erectile dysfunction prevalence, time of onset and association with risk factors in patients with acute chest pain and angiographically documented coronary artery disease. METHODS 300 consecutive patients with acute chest pain and angiographically documented coronary artery disease were assessed using a semi-structured interview investigating their medical and sexual histories, the International Index of Erectile Function and other instruments. RESULTS Patient mean age was 62.5+/-8 years (range 33-86 years). Mean duration of symptoms or signs of myocardial ischaemia prior to enrollment in the study was 49 months (range 1-200). Coronary angiography showed 1-, 2- and 3-vessel disease in 98 (32.6%), 88 (29.3%) and 114 (38%) patients, respectively. The prevalence of ED among all patients was 49% (147/300). Erectile dysfunction was scored as mild, mild to moderate, moderate and severe in 21 (14%), 31 (21%), 20 (14%), and 75 (51%) of patients, respectively. There was no significant difference between patients with ED (n=147) or without ED (n=153) as far as clinical and angiographic characteristics were concerned. In the 147 patients with co-existing ED and CAD, ED symptoms were reported as having become clinically evident prior to CAD symptoms by 99/147 (67%) patients. The mean time interval between the onset of ED and CAD was 38.8 months (range 1-168). There was no significant difference in terms of risk factor distribution and clinical and angiographic characteristics between patients with the onset of ED before vs. after CAD diagnosis. Interestingly, all patients with type I diabetes and ED actually developed sexual dysfunction before CAD onset (p<0.001). CONCLUSIONS Our study suggests that a significant proportion of patients with angiographically documented coronary artery disease have erectile dysfunction and that this latter condition may become evident prior to angina symptoms in almost 70% of cases. Future studies including a control group of patients with coronary artery disease and normal erectile function are required in order to verify whether erectile dysfunction may be considered a real predictor of ischemic heart disease.

Association of Insulin Resistance, Hyperleptinemia, and Impaired Nitric Oxide Release With In-Stent Restenosis in Patients Undergoing Coronary Stenting

Background—Previously undiagnosed diabetes, impaired glucose tolerance, and insulin resistance are common in patients with acute myocardial infarction and coronary heart disease (CHD) and might be involved in early restenosis after stent implantation. To evaluate whether markers of insulin resistance syndrome, including leptin, and endothelial dysfunction are related to increased rate of early restenosis, we studied nondiabetic patients with CHD after successful coronary stenting. Methods and Results—Both patients with CHD undergoing coronary stenting (120 patients) and control subjects (58 patients) were submitted to an oral glucose tolerance test (OGTT). Fasting leptin levels and fasting and postglucose load insulin sensitivity were assessed. Endothelial function was measured by nitrite and nitrate release (NOx) during OGTT. More than 50% of patients treated with stent implantation presented impaired glucose tolerance or type 2 diabetes, which was previously undiagnosed. These patients also had higher glucose, insulin, and leptin levels than control subjects. Among the stented patients, insulin and leptin levels were higher in patients with restenosis than in patients without restenosis. A significant increase in NOx levels was found during OGTT both in patients without restenosis and in control subjects. On the contrary, NOx profiles were blunted in patients with restenosis. At multiple regression analysis, only &Dgr;AUC-NOx areas and insulin sensitivity index showed an independent correlation with the minimal lumen diameter at follow-up. Conclusions—We demonstrated that insulin resistance and endothelial dysfunction are independent predictors of early restenosis after coronary stenting.

Acute Intravenous l-Arginine Infusion Decreases Endothelin-1 Levels and Improves Endothelial Function in Patients With Angina Pectoris and Normal Coronary Arteriograms Correlation With Asymmetric Dimethylarginine Levels

Background—We tested the hypothesis that asymmetric dimethylarginine (ADMA) levels could be elevated and influence endothelin-1 and nitric oxide release and action in patients with cardiac syndrome X (CSX). In addition, we evaluated whether an intravenous infusion of l-arginine would improve endothelial function in these subjects. Methods and Results—Nine patients with CSX and 14 control subjects underwent a continuous infusion of l-arginine (0.125 g/min) or saline for 120 minutes. Sixty minutes after l-arginine or saline infusions, an intravenous insulin bolus (0.1 U/kg) combined with a euglycemic clamp was performed. Basal ADMA and endothelin-1 levels were higher in patients with CSX than in controls. At the end of the first hour of infusion, compared with saline, l-arginine infusion increased basal forearm blood flow, nitrite and nitrate (NOx), and forearm cGMP release and decreased endothelin-1. After insulin bolus, during saline, insulin-induced NOx, endothelin-1, and forearm cGMP release was almost abolished. Conversely, l-arginine restored a physiological profile of all endothelial variables compared with control subjects. In control subjects, compared with saline infusion, l-arginine infusion did not modify any parameter. ADMA levels were positively correlated with basal endothelin-1 levels and negatively correlated with insulin-induced incremental levels of NOx and forearm cGMP release. Conclusions—Plasma ADMA levels are increased in patients with CSX, and they are correlated with increases in endothelin-1 and reductions in insulin-induced increments in plasma NOx and cGMP, effects that are reversed by intravenous l-arginine. These data suggest that increased ADMA levels play a role in the abnormal vascular reactivity that is observed in patients with CSX.

Specificity and sensitivity of exercise-induced ST segment elevation for detection of residual viability : comparison with fluorodeoxyglucose and positron emission tomography

OBJECTIVES We evaluated the sensitivity and specificity of exercise-induced ST segment elevation for the detection of residual myocardial viability. BACKGROUND Assessment of residual viability after myocardial infarction is relevant for establishing indication for revascularization. We have previously shown that exercise-induced ST segment elevation is a marker of residual viability. METHODS We studied 34 patients with a previous Q wave myocardial infarction (anterior in 21, inferior in 13) of whom 18 (group A) had exercise-induced ST segment elevation in more than one lead (mean [+/- SD] 1.8 +/- 0.9 mm, range 1 to 4) and 16 (group B) did not. All patients underwent rest technetium-99m methoxyisobutyl isonitrile single-photon emission computed tomography (SPECT), fluorine-18 (F-18) fluorodeoxyglucose positron emission tomography and coronary angiography. The time elapsed between the infarction and the viability study was 72 +/- 108 days (range 15 to 400) in group A and 516 +/- 545 days (range 14 to 1,800) in group B. RESULTS The presence and site of previous infarction were confirmed by SPECT studies in all 34 patients. Uptake of F-18 fluorodeoxyglucose within the infarcted area was present in 18 of 18 patients in group A but in only 9 (56%) of 16 in group B (p < 0.01). In patients with an anterior infarction, the sensitivity, specificity and predictive accuracy of exercise-induced ST segment elevation for detection of residual viability were 82%, 100% and 86%, respectively (95% confidence intervals 46% to 83.5%, 59% to 100% and 55.6% to 87.1%, respectively). CONCLUSIONS Exercise-induced ST segment elevation in infarct-related leads has a high specificity and acceptable sensitivity for detection of residual viability within the infarcted area.

Coronary Recanalization by Elective Angioplasty Prevents Ventricular Dilation After Anterior Myocardial Infarction

OBJECTIVES In a prospective study we evaluated whether late recanalization of the left anterior descending coronary artery (LAD) affects ventricular volume and function after anterior myocardial infarction. BACKGROUND Persistent coronary occlusion after anterior myocardial infarction leads to ventricular dilation and heart failure. METHODS We studied 73 consecutive patients with acute anterior myocardial infarction as a first cardiac event; all had an isolated lesion or occlusion of the proximal LAD. Six patients died before hospital discharge. The 67 survivors were classified into two groups: group I (patent LAD and good distal flow, n = 40) and group II (LAD occlusion or subocclusion, n = 27). The 20 patients in group I who had significant residual stenosis and all patients in group II underwent elective percutaneous transluminal coronary angioplasty (PTCA) within 18 days of myocardial infarction. The procedure was successful in 17 patients in group I (group IB) and in 16 patients in group II (group IIA): in the remaining 11 patients of group II, patency could not be reestablished (group IIB). Left ventricular volumes, ejection fraction and a dysfunction score were measured by echocardiography on admission, before PTCA, at discharge and after 3 and 6 months. RESULTS Although cumulative ST segment elevation was similar in groups I and II, ejection fraction and dysfunction score were significantly worse in group II. However, ventricular function and volumes progressively improved in group IIA, whereas group IIB exhibited progressive deterioration of function (dysfunction score [mean +/- SD] increased from 21 +/- 6 to 25 +/- 8, p < 0.05; ejection fraction decreased from 43 +/- 10% to 37 +/- 11%, p < 0.05); and end-systolic volume increased from 34 +/- 10 to 72 +/- 28 ml/m2, p < 0.05). Patients in group IIB also had worse effort tolerance, higher heart rate at rest, lower blood pressure and significantly greater prevalence of chronic heart failure. CONCLUSIONS Delayed PTCA of an occluded LAD can frequently restore vessel patency. Success appears to be associated with better ventricular function and a lack of chronic dilation. Large randomized studies are warranted to evaluate the effect of delayed PTCA on late mortality.

Pulsed tissue Doppler imaging detects early myocardial dysfunction in asymptomatic patients with severe mitral regurgitation

Objective: To assess whether tissue Doppler myocardial imaging (TDI) indices can predict postoperative left ventricular function in patients with mitral regurgitation (MR) after surgical correction. Methods: 84 patients (mean (SD) age 54.3 (10.8) years) with asymptomatic severe MR, an end systolic diameter < 45 mm, and an ejection fraction (EF) > 60% were subdivided in two groups: 43 patients with a postoperative EF reduction < 10% (group 1) and 41 patients with a postoperative EF reduction ⩾ 10% (group 2).TDI systolic indices of the lateral annulus were analysed preoperatively to assess myocardial systolic wave (Sm) velocity, myocardial precontraction time (PCTm), myocardial contraction time (CTm), and the PCTm:CTm ratio. Results: Postoperative EF decreased significantly (from 67 (5)% to 60 (5.5)%, p  =  0.0001). Group 2 had a higher PCTm, CTm, and PCTm:CTm ratio and a lower Sm velocity than group 1 (PCTm 100.4 (19) ms v 82 (21.8) ms, p  =  0.004; CTm 222 (3.1) ms v 215 (2.3) ms, p  =  0.01; PCTm:CTm 0.45 (0.08) v 0.38 (0.09), p  =  0.001; Sm velocity 10.4 (1.1) cm/s v 13 (1.3) cm/s, p  =  0.0001). Multivariate regression analysis showed that the combination of PCTm:CTm ratio ⩾ 40 ms and Sm velocity ⩽ 10.5 cm/s was the main independent predictor of postoperative EF reduction ⩾ 10% (sensitivity 78%, specificity 95%). Conclusions: TDI systolic indices can predict postoperative left ventricular function in patients with asymptomatic MR undergoing surgical correction.

Long‐term prognosis of medically treated patients with functional mitral regurgitation and left ventricular dysfunction

To assess long‐term prognosis in patients with functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction, receiving current standard pharmacological therapy.

Assessment of residual tissue viability by exercise testing in recent myocardial infarction: Comparison of the electrocardiogram and myocardial perfusion scintigraphy

The assessment of residual myocardial viability in infarcted areas is relevant for subsequent management and prognosis but requires expensive technology. To evaluate the possibility that simple, easily obtainable clinical markers may detect the presence of within-infarct viable tissue, the significance of exercise-induced ST elevation occurring in leads exploring the area of a recent Q wave myocardial infarction was assessed. Twenty-five patients with recent (less than 6 months) myocardial infarction were studied. All had angiographically documented coronary artery disease, diagnostic Q waves (n = 24) or negative T waves (n = 25) on the rest 12-lead electrocardiogram and exhibited during exercise greater than or equal to 1.5 mm ST segment elevation (n = 17) or isolated T wave pseudonormalization (n = 8) in the infarct-related leads. ST-T wave changes were reproduced in all patients during thallium-201 exercise myocardial scintigraphy. A fixed perfusion defect was observed in 24 of the 25 patients. A reversible defect was seen in 16 (94%) of 17 patients who exhibited transient ST elevation during exercise but in only 4 (50%) of the 8 patients who had only T wave pseudonormalization. In conclusion, in patients with recent myocardial infarction, analysis of simple ST segment variables obtained during exercise testing may allow a first-line discrimination of those who may potentially benefit from a revascularization procedure.

Effect of partial fatty acid oxidation inhibition with trimetazidine on mortality and morbidity in heart failure: Results from an international multicentre retrospective cohort study

OBJECTIVES The aim of this cohort study was to retrospectively evaluate, in patients with chronic heart failure (CHF), the long term effect of trimetazidine (TMZ) on morbidity and mortality. BACKGROUND Previous small studies in patients with CHF have shown that TMZ can improve left ventricular function, exercise capacity and NYHA class compared to placebo. However, no data on the effects of TMZ on survival in patients with CHF have ever been produced. METHODS In this international multicentre retrospective cohort study data from 669 patients were analyzed. 362 patients were on TMZ due to symptom persistence despite up-titration of optimal CHF therapy, while the remaining patients continued conventional CHF therapy alone. Propensity score analysis was performed in order to minimize selection bias between the two groups. RESULTS Kaplan-Meier analysis for global mortality showed 11.3% improved global survival (p=0.015) and 8.5% improved survival for cardiovascular (CVD) death (p=0.050) in the TMZ group. Cox regression analysis for global mortality showed a significant risk reduction for TMZ treated patients with a hazard ratio (HR)=0.189 (confidence interval - CI 95%: 0.017-0.454; p=0.0002). TMZ also showed a good risk reduction profile for CVD death causes (HR=0.072, CI 95%: 0.019-0.268, p=0.0001). The rate of hospitalization for cardiovascular causes was reduced by 10.4% at 5 years (p<0.0005) with increased hospitalization-free survival of 7.8 months. CONCLUSION TMZ is effective in reducing mortality and event-free survival in patients with CHF. The addition of TMZ on top of optimal medical therapy improves long term survival in CHF patients.

Role of regional mechanical dyssynchrony as a determinant of functional mitral regurgitation in patients with left ventricular systolic dysfunction

Objective: To assess regional mechanical dyssynchrony as a determinant of the degree of functional mitral regurgitation (FMR). Setting: Tertiary cardiology clinic. Patients: 74 consecutive patients with left ventricular (LV) dysfunction (ejection fraction < 40%, mean 32.2 (SD 7.3)%) were evaluated. Methods: Effective regurgitant orifice (ERO) area, indices of mitral deformation (systolic valvular tenting, mitral annular contraction) and of global LV function and remodelling (ejection fraction, end systolic volume, sphericity index) and local remodelling (papillary-fibrosa distance, regional wall motion score index), and tissue Doppler-derived dyssynchrony index (DI) (regional DI, defined as the standard deviation of time to peak myocardial systolic contraction of eight LV segments supporting the papillary muscles attachment) were measured. Results: All the assessed variables correlated significantly with ERO. By multivariate analysis, systolic valvular tenting was the strongest independent predictor of ERO (R2  =  0.77, p  =  0.0001), with a minor influence of papillary-fibrosa distance (R2  =  0.77, p  =  0.01) and regional DI (R2  =  0.77, p  =  0.03). Local LV remodelling (regional wall motion score index: R2  =  0.58, p  =  0.001; papillary-fibrosa distance: R2  =  0.58, p  =  0.002) and global remodelling indices (sphericity index: R2  =  0.58, p  =  0.003) were the main determinants of systolic valvular tenting, whereas regional DI did not enter into the model. Regional DI was an independent predictor of ERO (R2  =  0.56, p  =  0.005) in patients with non-ischaemic LV dysfunction but not in patients with ischaemic LV dysfunction when these groups were analysed separately. Conclusions: The degree of FMR is associated mainly with mitral deformation indices. The regional dyssynchrony also has an independent association with ERO but with a minor influence; however, it is not a determinant of FMR in patients with ischaemic LV dysfunction.