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Background: Adults with CHD often exhibit complex cardiac abnormalities, whose management requires specific clinical and surgical expertise. To enable easier access of these patients to highly specialised care, we implemented a collaborative programme that incorporates medical and surgical specialists belonging to both paediatric and adult cardiovascular institutions., Objectives: The objective of this study was to review the experience gained and to analyse the surgical outcome of major cardiac surgery., Methods: We retrospectively reviewed all consecutive patients admitted for major cardiac surgery using our network between January, 2010 and December, 2013. Analysis of surgical outcome was performed in patients selected for major cardiac surgery with cardiopulmonary bypass. Early and late outcomes were evaluated., Results: Out of a total of 433 inward patients, 86 were selected for surgery. The median age was 25.5 years, -64 patients (74.4%) had previously undergone heart surgery, and -55 patients (64%) had been subjected to at least one sternotomy. Abnormalities of the left ventricular and right ventricular outflow tract were the most frequent (37.2% and 30.2%, respectively), and despite high-surgical complexity only one death occurred (in-hospital mortality 1.1%). On a median follow-up time of 4 years no deaths and no heart-failure events have occurred; one patient underwent further cardiac surgery programmed at the time of discharge., Conclusions: Low mortality and morbidity rates can be obtained in high-surgical complexity adults with CHD populations when paediatric and adult cardiac specialists operate in the same multidisciplinary environment.

Background: Although an increasing number of symptomatic patients with atrial fibrillation (AF) are being treated with percutaneous radiofrequency ablation, the actual long-term success rate of this procedure remains uncertain. The increasing availability of minimally invasive techniques has made surgery progressively more appealing, especially because of its superior capacity to create transmural lesions., Methods: In a group of 46 patients with paroxysmal or persistent "lone" AF, who were refractory to medical treatment or had arrhythmia recurrences after a transcatheter procedure, we performed epicardial radiofrequency ablation by a minimally invasive, monolateral thoracoscopic approach. Mean operative time was 85 +/- 35 minutes, and intensive care unit and hospital stays were, respectively, 18.7 +/- 5.1 hours and 4.1 +/- 1.4 days. There were no deaths and only 1 serious complication due to severe bleeding requiring conversion to median sternotomy., Results: At the 6-month follow-up (Holter monitoring), 40 patients (87%) were in stable sinus rhythm. Of the 6 recurrences that we observed, 5 occurred in patients with persistent AF and 1 in a patient with paroxysmal AF (p < 0.01)., Conclusions: Minimally invasive monolateral thoracoscopic radiofrequency ablation is safe and apparently effective. If these findings are confirmed on larger populations followed for longer periods, this procedure may become a viable proposal for treating refractory lone AF., (Copyright 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

To assess the performance of currently used stress tests for the detection of coronary artery disease (CAD) in a series of female hypertensive patients. We performed exercise electrocardiography (ECG), technetium-99m sestamibi (MIBI) single photon emission computed tomography, dobutamine and dipyridamole echocardiography, and coronary angiography in 76 hypertensive women. Of the 76 study patients, 31 (41%) had significant CAD. The sensitivity of exercise ECG (81%), MIBI scanning (90%), and dobutamine echocardiography (87%) was greater than that of dipyridamole echocardiography (61%). This finding resulted from the lower sensitivity of dipyridamole echocardiography in the detection of single-vessel CAD (47% vs 76%, 88%, and 82% for the other 3 methods). In contrast, the sensitivity of the 4 tests was similar in the detection of multivessel CAD. The specificity of exercise ECG (56%) and MIBI scanning (53%) was less than that of dobutamine (82%, both p <0.01) and dipyridamole (91%, both p <0.001) echocardiography. This finding related to the lower specificity of exercise ECG in patients with either left ventricular hypertrophy or ST-T abnormalities at rest compared to the specificity in patients without these disorders (33% vs 89%, p <0.01). A lower MIBI scan specificity was found only in patients with left ventricular hypertrophy (31% vs 66%, p <0.05). The overall accuracy of dobutamine echocardiography reached 84% compared to exercise ECG (66%, p <0.01), MIBI scan (68%, p <0.05), and dipyridamole echocardiography (79%, p <0.05). In conclusion, dobutamine echocardiography yielded satisfactory diagnostic accuracy for identifying CAD in hypertensive women. Although dipyridamole echocardiography had the greatest specificity, it might be limited in detecting mild CAD. Both exercise ECG and MIBI scanning had fare sensitivity; however, our findings limit the usefulness of these 2 tests in unselected patients., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to evaluate enoximone echocardiography (EE) for the identification of residual myocardial viability in postinfarction patients. Findings obtained during EE were compared with those acquired by myocardial uptake of fluorine-18 fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) and functional follow-up results., Methods: Twenty-five patients underwent EE and PET (18)F-FDG studies. An asynergic segment was considered as having contractile enhancement when the wall motion score decreased by > or = 1 grade during EE and was defined as viable if (18)F-FDG uptake score was > or = 2 grade on PET., Results: Of 293 dysfunctional segments at baseline, 139 (47%) were viable by PET criteria; 117 (40%) had contractile enhancement induced by enoximone (P = 0.07). Agreement between EE and PET was found in 75% of involved segments (K = 0.46, P < 0.001). The majority of discrepancies (65%, P < 0.01) were mainly due to discordant segments in which PET revealed evidence of (18)F-FDG uptake but EE showed no change in wall motion. In 179 revascularized segments, negative predictive value for functional recovery of both tests reached the same value (89% for both), whereas positive predictive value was 82% for EE and 68% for PET, respectively (P < 0.05). Sensitivity was 85% for EE and 88% for PET (P = ns); specificity was 87% and 70%, respectively (P < 0.01)., Conclusions: EE yields a fair concordance with PET study. Compared with PET, despite a similar negative accuracy, EE shows a greater specificity for prediction of function recovery after revascularization. (Echocardiography 2010;27:544-551).

Background: We investigated the possibility that transient coronary slow-flow as assessed during coronary angiography in patients with cardiac syndrome X may impair myocardial perfusion and the effects of this phenomenon on long-term prognosis., Methods: From 50 consecutive patients with cardiac syndrome X, we prospectively recruited 16 who exhibited coronary slow-flow during angiography. The remaining 34 patients served as controls. The slow-flow phenomenon was invariably worsened by nitrates and reversed by papaverine. During slow-flow, a dose of 99m-Tc-Methoxy-isobutyl-isonitrile (MIBI) was injected in 12 patients and SPECT imaging performed 1 h later. The perfusion study was repeated after 2 days at rest and, in 9 patients, at peak exercise after 10+/-4 days. Patients were then regularly followed-up., Results: All 12 patients had a significant MIBI defect in the regions served by the coronary artery that showed slow-flow just prior MIBI injection. After exercise, MIBI tomograms revealed a perfusion defect in 5 out of the 9 patients who underwent stress scanning. At 14+/-2 years follow-up, 1 patient with slow-flow had died and 4 developed significant coronary artery disease (CAD), while all patients of the control group were alive and none had developed significant CAD., Conclusions: These results show that the slow-flow phenomenon might be the cause of transient myocardial underperfusion in patients with angina and normal coronary arteries. Apparently, this phenomenon is associated with a worse cardiac prognosis. Therefore, patients with coronary slow-flow should be carefully followed-up.

Thirteen hypertensive patients with microvascular angina were studied before and after receiving oral L-arginine (4 weeks, 2 g, 3 times daily). L-arginine significantly improved angina class, systolic blood pressure at rest, and quality of life. Maximal forearm blood flow, plasma L-arginine, L-arginine:asymmetric dimethyl arginine ratio, and cyclic guanylate monophosphate increased significantly after treatment. In medically treated hypertensive patients with micro-vascular angina, oral L-arginine may represent a useful therapeutic option.

Background: There are no published data in the literature on the scintigraphic perfusion pattern in patients with myocardial infarction (MI) and normal coronary arteries (NCA)., Objectives: To evaluate myocardial perfusion imaging in a series of patients with MI and NCA., Methods: Twenty-seven patients who had developed a MI and had NCA were studied. As a control group we included 27 patients with a recent MI and coronary artery disease (CAD). All patients underwent stress/rest tetrofosmin myocardial perfusion SPECT within 6 months from MI., Results: In patients with NCA tetrofosmin stress images revealed 41 hypoperfused segments in 17 patients (63%). On rest images, 13 segments remained unchanged, 4 showed partial reperfusion, 10 normalized and 14 worsened. Additionally, there were 18 new hypoperfused segments in nine patients. Therefore, perfusion worsened at rest in 18 patients (67%) (32 segments). Overall, at rest there were 49 hypoperfused segments in 22 patients (81%). In patients with CAD, stress images revealed 71 hypoperfused segments. On rest images, 39 segments remained unchanged, 16 showed partial reperfusion and 12 normalized. Four segments worsened at rest and only four patients (15%) showed new perfusion defects at rest., Conclusions: Myocardial perfusion with tetrofosmin might appear considerably worse at rest than at stress in patients with MI and NCA. Specifically, a reverse perfusion pattern in the infarct area is a frequent finding and is likely to be due to residual tissue viability. We postulate that in these patients the hyperemic response to exercise may mask resting underperfusion areas.

Background: It has been suggested that phosphodiesterase 5 (PDE5) inhibition is potentially hazardous and that it increases the risk of cardiac events in patients with coronary artery disease. This study sought to evaluate whether PDE5 inhibition with sildenafil exerts any effect on exercise-induced myocardial ischemia in patients on beta-blockers., Methods: Fourteen patients underwent a baseline exercise test off-therapy and were then started on atenolol (100 mg once daily). After a run-in phase of 1 week, patients underwent a second exercise test and were randomized to receive either sildenafil (50 mg) or placebo given in a random order on two different occasions, 2 days apart. Exercise test was repeated 2 hours after the administration of sildenafil or placebo., Results: All patients had a > 1 mm ST-segment depression while off-therapy. Eight patients had a negative exercise test response after atenolol, which was unaltered by the adjunct of either sildenafil or placebo. In the remaining subjects, atenolol significantly prolonged the time to 1 mm ST-segment depression and the exercise time. Sildenafil and placebo did not reverse the beneficial effect of atenolol upon exercise-induced myocardial ischemia., Conclusions: PDE5 inhibition does not worsen exercise capacity and exercise-induced myocardial ischemia in patients with chronic stable angina whose symptoms and exercise test response are well controlled by beta-blocker therapy.

Background: Although in experimental models of coronary occlusion diltiazem administration has been shown to reduce the degree of stunning and of reperfusion injury, the majority of clinical trials has failed to demonstrate significant benefits. The aim of this study was to evaluate the effect of diltiazem, administered before coronary reperfusion, on infarct size, residual myocardial viability and recovery of left ventricular function., Methods: We studied 90 patients admitted within 3 hours of the onset of symptoms of acute myocardial infarction. They were immediately randomized to either intravenous diltiazem (10 mg bolus + 10 mg/hour for 3 days) (group 1, n = 43) or placebo (group 2, n = 47) and subsequently treated with recombinant tissue-type plasminogen activator. All underwent serial echocardiograms upon admission, 4 days post-admission during low-dose dobutamine stress echo, at discharge and after 6 months. We calculated the dysfunction score (1 = hypokinesia, 2 = akinesia, 3 = dyskinesia) on admission and its percent reduction after dobutamine (viability) and at follow-up (recovery). The 12-lead electrocardiograms were continuously monitored for 3 days and coronary angioplasty was performed whenever the residual stenosis was > 60%., Results: Upon admission, there were no differences in age, sex, infarct location and size, degree of ST-segment elevation, time from onset of symptoms and dysfunction score. Creatine kinase peaked early in 70% of patients in both groups; the incidences of recurrent ischemia, infarct-related vessel patency and the need for coronary angioplasty were also similar. The creatine kinase peak was significantly higher in group 2 (2931 +/- 2456 vs 1726 +/- 1004 IU/l, p < 0.05). Conversely, in group 1 the residual viability was significantly higher (51 +/- 23 vs 36 +/- 30% improvement in dysfunction score, p < 0.05) and the early recovery of regional function was significantly greater (35 +/- 34 vs 18 +/- 22% at discharge, p < 0.05). On the other hand, the delayed recovery was not significantly different (15 +/- 29 vs 21 +/- 32% from the time of discharge to 6 months of follow-up)., Conclusions: Intravenous diltiazem, started before coronary reperfusion, has beneficial effects on the infarct size, residual viability and recovery of regional function. If confirmed by larger trials, these preliminary results suggest the use of diltiazem as adjunctive therapy in patients with acute myocardial infarction and undergoing reperfusion.

Objectives: We sought to evaluate the importance of time in relation to treatment, time course and determinants of recovery of left ventricular (LV) function in patients with acute myocardial infarction (AMI) undergoing primary percutaneous transluminal coronary angioplasty (PTCA)., Background: Myocardial salvage has been shown to be dependent on the time elapsed from the onset of AMI to reperfusion., Methods: Left ventricular function was evaluated at hospital admission, after angioplasty, at 24 h and 6 months by both echocardiography and angiography and at 1, 7, 30, 90 and 180 days by echocardiography in 101 consecutive patients., Results: Patients were allocated to three groups according to interval between symptom onset and angioplasty: <2 h (group A), 2 to 4 h (group B) and >4 h (group C). Patients in groups A and B showed a progressive improvement of LV function between day 7 and day 90, which became statistically significant at day 30 (p < 0.01). No LV function changes were noted in group C patients. Thrombolysis In Myocardial Infarction (TIMI) flow grade <3 at 24 h was not associated with any significant change in LV volume and function during the six-month follow-up period. Restenosis, when associated with TIMI flow grade 3 in the infarct-related vessel, did not influence LV function. Flow grade <3 of the infarct-related artery was not associated with any improvement of cardiac events independently from the time to treatment at the initial procedure., Conclusions: Patients undergoing primary PTCA for AMI have a good recovery of LV function if TIMI flow grade 3 is restored within 4 h. Coronary angioplasty limits further remodeling of the LV in patients treated after 4 h.

Phosphatidylinositol 3-kinase (PI-3K) controls important intracellular steps involved in inflammation, immunity, and cell growth. PI-3K also modulates leukocyte integrin adhesiveness. In this study we evaluated the role of PI-3K on neutrophil adhesion to intercellular adhesion molecule-1 (ICAM-1)-transfected cells. N-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated neutrophil adhesion was inhibited by wortmannin and LY294002, two unrelated PI-3K inhibitors, whereas phorbol myristate acetate (PMA)-induced neutrophil adhesion was not inhibited by them. After fMLP stimulation, a rapid activation of AKT and ERK was observed. However, only activation of AKT was reversed by the PI-3K inhibitors. Neutrophil expression of the beta2-integrins Mac-1, lymphocyte function-associated antigen-1(LFA-1), and gp150.95 was not affected by wortmannin, nor was expression of the activation epitope recognized by MAB24. We conclude that (a) PI-3K is involved in fMLP-activated neutrophil adhesion to ICAM-1-transfected cells, (b) the mechanism involved is not mediated by the modulation of beta2-integrin expression or activation, and (c) another mechanism seems to involve the adhesion to ICAM-1 when a cellular system of adhesion is used.

Background: Myocardial salvage has been shown to be dependent on the time elapsed from the onset of acute myocardial infarction (AMI) to reperfusion. The aim of this study was to evaluate the importance of time to reperfusion for left ventricular function recovery after primary angioplasty (percutaneous transluminal coronary angioplasty [PTCA]) for AMI., Methods: Ninety-five patients undergoing long-term successful PTCA for AMI were studied. Echocardiography was performed before and 3, 7, 30, 90, and 180 days after PTCA. End-diastolic volume index (EDVI) and end-systolic volume index (ESVI), ejection fraction, and left ventricular wall motion score index (WMSI) were evaluated., Results: Patients were divided into group A, 23 patients reperfused within 2 hours; group B, 32 patients reperfused between 2 and 4 hours; group C, 22 patients reperfused between 4 and 6 hours; and group D, 18 patients reperfused between 6 and 12 hours. Both EDVI and ESVI were reduced in groups A and B at 90 days. Groups C and D did not show any changes of EDVI and ESVI at any stage throughout the study. Ejection fraction improved only in groups A and B at 30, 90, and 180 days. At study entry, WMSI was similar in all groups. After 7 days, in group A and in group B, WMSI was improved, no changes were observed in group C, and a mild deterioration was observed in group D at 3 and 7 days. Subsequent evaluations showed progressive improvement of WMSI in all groups., Conclusions: Myocardial salvage is achieved only in patients revascularized within 4 hours from AMI onset. However, revascularization after 6 hours may be worthwhile by preventing ventricular remodeling.

Trimetazidine, a metabolic agent that is opening the way to a new class of 3-ketoacyl coenzymeA thiolase inhibitors, has been shown to improve exercise tolerance and increase the ischaemic threshold in patients with effort angina, both in monotherapy or in combination with other anti-anginal drugs. The aim of this study was to assess the effects of oral trimetazidine on the ischaemic threshold and left ventricular dysfunction of patients with coronary artery disease. Dobutamine stress echocardiography was used, a technique that allows direct visualisation of localised left ventricular dysfunction that occurs as a result of ischaemia. Dobutamine increases heart rate and contractility thus augmenting oxygen demand. In coronary artery disease, this increased demand leads to metabolic changes responsible for decreased wall thickness and abnormal wall motion.

Sixteen postmenopausal women underwent electrophysiologic study before and 20 minutes after the administration of sublingual estradiol 17beta or placebo. Estradiol 17beta significantly affected electrophysiologic parameters, thereby suggesting its role in the development of palpitations in women.

Background: The syndrome of variant angina occurs in patients with a wide spectrum of coronary disease ranging from angiographically normal coronary arteries to severe three-vessel disease. Survival and choice of therapy for these patients are determined by the extent of underlying fixed coronary obstruction. We examined whether heart rate variability (HRV) due to reduced vagal outflow may correlate with the severity of coronary stenoses in such patients., Methods: Fifteen men and 2 women with clinically unstable variant angina underwent 24-hour Holter monitoring from which low and high-frequency power, standard deviation of mean 24-hour RR interval, proportion of adjacent RR intervals that differed by more than 50 ms, and mean root square of differences between successive RR intervals were extracted by power spectral analysis. Coronary angiography was later performed to determine coronary pathology and verify variant angina. As controls we studied an age-matched control group of 8 subjects (5 men, 3 women) with no clinical and/or electrocardiographic evidence of coronary heart disease or spasm as shown by negative treadmill exercise and hyperventilation tests., Results: All measured components of HRV were significantly lower in the 9 patients with severe coronary artery disease compared to the 8 patients with normal coronary arteries or < 40% stenosis. The two groups were otherwise similar in terms of age and clinical parameters., Conclusions: These preliminary findings on a small but carefully selected group of patients with variant angina indicate that the analysis of HRV can select patients with severe disease for a more intensive approach. These findings require confirmation on a larger patient series.

Background: Recent studies have indicated that heparin administration might decrease endothelial nitric oxide production. The aim of this study was to investigate the effect of heparin on ischemic threshold., Methods: Eighteen patients with a positive exercise test and proven coronary artery disease were submitted to a randomized, placebo-controlled trial using i.v. 0.9% NaCl as placebo and i.v. heparin (5,000 IU bolus + 1,000 IU/h). After both saline and heparin bolus, the infusion was started and, after 10 min, the exercise test was performed. Blood samples for nitric oxide metabolites and free fatty acid determinations were taken before, at peak exercise, and at ECG recovery., Results: As compared to placebo, heparin significantly decreased time to 1 mm ST segment depression (241 +/- 160 vs 303 +/- 175 s, p = 0.003) and prolonged recovery (573 +/- 177 vs 441 +/- 195 s, p = 0.003), while exercise duration was similar. Accordingly, rate-pressure product at 1 mm ST segment depression was lower after heparin, while it was similar at peak exercise. No significant differences were found for plasma nitric oxide metabolite levels. Conversely, free fatty acid levels were higher after heparin throughout the study in all patients. The increase in free fatty acids was not correlated with the difference in rate-pressure product at 1 mm ST segment depression between placebo and heparin (r = 0.34, p = NS)., Conclusions: In patients with stable coronary artery disease, heparin significantly decreased exercise ischemic threshold. The lower rate-pressure product at 1 mm ST segment depression during heparin, compared to placebo, suggests an impairment of coronary blood flow, which does not seem to be mediated by decreased nitric oxide production/release. The increased free fatty acid release, on the other hand, might contribute to the detrimental effect of heparin on exercise-induced ischemia, but the lack of a correlation with changes in ischemic threshold suggests that other, still unknown, factors are involved.

Background: The possibility that enoximone, a nonglycoside, noncatechol, positive inotropic agent, in combination with 2-dimensional echocardiography may predict recovery of myocardial dysfunction after revascularization has not been yet evaluated., Methods and Results: Forty-five patients with chronic coronary artery disease and left ventricular dysfunction underwent dobutamine (DE, 5 to 10 microg. kg(-1). min(-1)) and enoximone (EE, 1.5 mg/kg, over 10 minutes) echocardiography. Myocardial wall motion was scored from 1 (normal) to 4 (dyskinesia): an asynergic segment was considered to have contractile enhancement when the score decreased by >/=1 grade. Of 478 asynergic segments, 216 (45%) exhibited functional recovery after revascularization. Dobutamine- and enoximone-induced contractile enhancement was observed in 41% and 46% of segments, respectively. Compared with DE, EE had higher sensitivity (88% versus 79%, P<0.01) and negative predictive value (90% versus 84%, P<0.05) in predicting functional recovery. The specificity (89% versus 90%) and positive predictive value (87% for both EE and DE) were similar. Concordant interpretation of EE and DE findings was found in 85% (406 of 478) of affected segments. Prerevascularization coronary angiography showed that stenosis severity of vessels supplying areas which only improved with enoximone was significantly greater (89.9%) than that of vessels (77.7%) supplying areas that responded to both agents (P<0.02). Both dobutamine and enoximone increased heart rate (16% and 10%, respectively), whereas enoximone did not cause changes in systolic blood pressure that increased by 14% with dobutamine., Conclusions: Enoximone echocardiography provides a novel and reliable approach for the prediction of functional recovery after revascularization. Compared with dobutamine echocardiography, the test yields higher sensitivity and induces lesser hemodynamic alterations.

Context: Controversy surrounds the diagnostic and prognostic importance of slightly elevated cardiac markers in patients with acute coronary syndromes without ST-segment elevation., Objectives: To investigate the relationship between peak creatine kinase (CK)-MB level and outcome and to determine whether a threshold CK-MB level exists below which risk is not increased., Design and Setting: Retrospective observational analysis of data from the international Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, conducted from November 1995 to January 1997., Patients: A total of 8250 patients with acute coronary syndromes without ST-segment elevation who had at least 1 CK-MB sample collected during their index hospitalization., Main Outcome Measure: Mortality at 30 days and 6 months, was assessed by category of index-hospitalization peak CK-MB level (0-1, >1-2, >2-3, >3-5, >5-10, or >10 times the upper limit of normal). Multivariable logistic regression was used to determine the independent prognostic significance of peak CK-MB level after adjustment for baseline predictors of 30-day and 6-month mortality., Results: Mortality at 30 days and 6 months increased from 1.8% and 4.0%, respectively, in patients with normal peak CK-MB levels, to 3.3% and 6.2 % at peak CK-MB levels 1 to 2 times normal, to 5.1% and 7.5% at peak CK-MB levels 3 to 5 times normal, and to 8.3% and 11.0% at peak CK-MB levels greater than 10 times normal. Log-transformed peak CK-MB levels were predictive of adjusted 30-day and 6-month mortality (P<.001 for both)., Conclusions: Our data show that elevation of CK-MB level is strongly related to mortality in patients with acute coronary syndromes without ST-segment elevation, and that the increased risk begins with CK-MB levels just above normal. In the appropriate clinical context, even minor CK-MB elevations should be considered indicative of myocardial infarction.

Background: Trimetazidine has been shown to improve anginal symptoms without altering hemodynamic variables in patients with coronary artery disease. The aim of this study was to compare the effect of trimetazidine and atenolol upon symptoms, resting left ventricular filling dynamics and exercise tolerance., Methods: Sixteen patients (3 males, 13 females, mean age 62 +/- 7 years) were randomized to receive trimetazidine for 2 weeks (20 mg 3 times daily) or atenolol (100 mg daily), according to a double-blind, randomized, cross-over, placebo-controlled design. At the end of each treatment period patients underwent symptom-limited exercise testing, an echocardiogram and a Doppler assessment of transmitral flow pattern. Daily life anginal symptoms were annotated on a diary throughout the study. Two patients discontinued trimetazidine because of severe palpitations and only 14 patients completed the study., Results: Atenolol significantly reduced the number of anginal episodes as compared to placebo or trimetazidine (0.44 +/- 0.53, 4.8 +/- 4, 2.9 +/- 4.9, p < 0.01). On atenolol, the exercise test was negative in 8 patients, but none of the patients had a negative test while on trimetazidine. Atenolol increased both time to 1 mm ST segment depression (668 +/- 213 vs 838 +/- 81 s, p < 0.05) and Doppler-derived indices of ventricular filling (E/A ratio 0.87 +/- 0.20 vs 1.21 +/- 0.26, p < 0.05)., Conclusions: These results confirm the beneficial effects of atenolol in improving symptoms, exercise performance and diastolic function in syndrome X patients. Trimetazidine did not exert any significant effect on any of the analyzed variables. Since trimetazidine has been previously shown to improve myocardial ischemia in patients with overt coronary artery disease to a similar extent of beta-blockers, it is likely that other mechanisms are responsible for angina in patients with syndrome X.

Objectives: We assessed the short- and long-term clinical and angiographic outcome of nonocclusive unstented dissection after percutaneous transluminal coronary angioplasty (PTCA) and its correlation with restenosis., Background: The use of stents has dramatically increased both the number and the cost of coronary revascularization procedures. However, this technique is not completely risk free, and its benefits have not been fully demonstrated in uncomplicated dissections., Methods: We studied 129 consecutive patients with 49 nonocclusive dissections after PTCA (grades A to D of National Heart, Lung, and Blood Institute classification) and good distal flow (TIMI [Thrombolysis in Myocardial Infarction] flow grade 3). All patients underwent coronary angiography at 24 h and at six months post-PTCA. Clinical status was assessed every three months in the outpatient clinic. Study subjects were matched with 60 other patients in whom stenting was performed for the presence of dissection., Results: In the former group, all but two patients (with type E dissection, which evolved to coronary occlusion and myocardial infarction) improved their dissection score during follow-up: at six months only 18 dissections were still angiographically visible, and no clinical adverse events were recorded. In the dissected vessels, the restenosis rate was significantly lower than in those without dissection (12% vs. 44%, p < 0.001); in the stented vessels, the restenosis rate was 25% (15/60)., Conclusions: In the presence of TIMI flow grade 3, coronary dissection is associated with a favorable outcome and predicts a low restenosis rate. These results caution against the indiscriminate use of intravascular prostheses in the event of nonocclusive coronary dissection.

Objectives: Although different noninvasive tests have been proposed for detecting coronary artery disease (CAD) in patients with hypertension and chest pain symptoms, the relative performance of the available techniques has not been systematically assessed., Background: Patients with hypertension frequently complain of chest pain and exhibit ischemic-like ST segment changes on the exercise electrocardiogram (ECG). However, the specificity of such changes for predicting significant CAD is very low, because these patients often exhibit a normal coronary angiogram., Methods: In 101 patients with hypertension, chest pain and positive exercise ECG, we performed stress/rest myocardial single photon emission computed tomography with 99mTc-MIBI, dipyridamole and dobutamine stress echocardiography and coronary angiography. All patients had normal global ventricular function and 57 had left ventricular hypertrophy. All were kept on ACE inhibitors during the study period., Results: No patients had significant side effects during perfusion scintigraphy. Dose-limiting side effects were observed in five patients with dipyridamole and in seven patients with dobutamine. Only 56% of study patients exhibited significant CAD. Sensitivity, specificity, accuracy, positive and negative predictive values were, respectively, 98%, 36%, 71%, 67% and 94% for perfusion scintigraphy, 61%, 91%, 74%, 90% and 64% for dipyridamole and 88%, 80%, 84%, 85% and 83% for dobutamine stress echocardiography., Conclusions: This study shows that stress echo in patients with hypertension yields a satisfactory diagnostic accuracy for identifying significant epicardial CAD. Our results indicate that dobutamine might be superior to dipyridamole. The low specificity of myocardial scintigraphy probably relates to the fact that this method traces perfusion abnormalities, not necessarily caused by epicardial CAD, possibly due to microvascular disease and not causing obvious wall motion abnormalities.

Background: The syndrome of angina and normal coronary arteries (syndrome X) comprises a heterogeneous group of patients with typical chest pain, a positive exercise test, angiographically smooth coronary arteries and no evidence of spasm. Magnetic resonance imaging (MRI) has been used to detect areas of myocardial ischemia and/or recent necrosis both in animal and human studies. Most of these studies have been conducted after intravenous administration of the paramagnetic contrast medium gadolinium-DTPA (Gd-DTPA), that is considered a sensitive marker of extracellular, probably ischemic in origin, edema. On the basis of these data, we used MRI to evaluate the possibility of myocardial Gd-DTPA deposition at rest in patients with syndrome X, and to assess the effects of oral treatment with atenolol., Methods: We have studied 24 patients with syndrome X, 10 patients with coronary artery disease and 10 age-matched control subjects. The protocol was similar in all study subjects. Exercise testing and MRI were undertaken off therapy after coronary arteriography. Following MRI, patients underwent a 10 day treatment period with atenolol and repeated exercise stress test and MRI while on therapy., Results: In all patients with syndrome X and coronary artery disease were observed effort diagnostic ST-segment changes that were associated with angina in 9 (37%) and 7 (70%) patients, respectively. Of 24 patients with syndrome X, 16 (66.6%) showed areas of myocardial enhancement after Gd-DTPA in comparison to the precontrast imaging. In 4 out of 10 patients with coronary artery disease (40%), Gd-DTPA accumulation was documented. Finally, focal Gd-DTPA myocardial enhancement was not observed in any normal control subject. After beta-blockade, 22 (92%) patients with syndrome X and 2 (20%) with coronary artery disease did not show any ischemic ST-segment changes on effort; 14 syndrome X patients (88%) and 2 coronary artery disease patients (50%) showed complete disappearance of the previously Gd-DTPA enhanced areas on MRI., Conclusions: Patients with syndrome X often exhibit regional accumulation of Gd-DTPA on MRI. The agent is believed to trace interstitial water accumulation as occurs during ischemia and its accumulation is reduced or abolished by treatment with atenolol, probably by different mechanisms. It is likely that an overactivation of the sympathetic outflow to the cardiovascular system can induce most of the abnormalities observed in syndrome X patients. In this context, beta-blockers probably represent the mainstay of the medical treatment of this condition.

Background: The role of testosterone on the development of coronary artery disease in men is controversial. The evidence that men have a greater incidence of coronary artery disease than women of a similar age suggests a possible causal role of testosterone. Conversely, recent studies have shown that the hormone improves endothelium-dependent relaxation of coronary arteries in men. Accordingly, the aim of the present study was to evaluate the effect of acute administration of testosterone on exercise-induced myocardial ischemia in men., Methods and Results: After withdrawal of antianginal therapy, 14 men (mean age, 58+/-4 years) with coronary artery disease underwent 3 exercise tests according to the modified Bruce protocol on 3 different days (baseline and either testosterone or placebo given in a random order). The exercise tests were performed 30 minutes after administration of testosterone (2.5 mg IV in 5 minutes) or placebo. All patients showed at least 1-mm ST-segment depression during the baseline exercise test and after placebo, whereas only 10 patients had a positive exercise test after testosterone. Chest pain during exercise was reported by 12 patients during baseline and placebo exercise tests and by 8 patients after testosterone. Compared with placebo, testosterone increased time to 1-mm ST-segment depression (579+/-204 versus 471+/-210 seconds; P<0. 01) and total exercise time (631+/-180 versus 541+/-204 seconds; P<0. 01). Testosterone significantly increased heart rate at the onset of 1-mm ST-segment depression (135+/-12 versus 123+/-14 bpm; P<0.01) and at peak exercise (140+/-12 versus 132+/-12 bpm; P<0.01) and the rate-pressure product at the onset of 1-mm ST-segment depression (24 213+/-3750 versus 21 619+/-3542 mm Hgxbpm; P<0.05) and at peak exercise (26 746+/-3109 versus 22 527+/-5443 mm Hgxbpm; P<0.05)., Conclusions: Short-term administration of testosterone induces a beneficial effect on exercise-induced myocardial ischemia in men with coronary artery disease. This effect may be related to a direct coronary-relaxing effect.

Aims: A sizeable proportion of patients with angina, angiographically smooth coronary arteries and positive exercise test (syndrome X) have stress/rest myocardial perfusion defects. The aim of the study was to assess whether perfusion defects are dependent upon a reduction in coronary flow reserve causing regional left ventricular dysfunction in syndrome X patients., Methods and Results: Twenty-two syndrome X patients underwent dobutamine stress echocardiography (DSE). All had stress-induced perfusion defects documented by 99m-Tc-MIBI scintigraphy. Resting and peak DSE wall motion score index (WMSI) were evaluated. Six patients exhibited resting wall motion abnormalities in 10 segments (WMSI 1.05 +/- 0.11). DSE was positive in 12 patients (53%), in whom 16 myocardial segments were involved: of these, 12 were normokinetic and 4 hypokinetic at rest. Peak WMSI was 1.17 +/- 0.17 (p < 0.05 vs rest). Of the 12 patients with a positive DSE, 9 also showed diagnostic ECG changes and 6 complained of angina. Of the 10 patients with negative DSE, 5 had angina and 5 (one with angina) showed ECG changes. In 7 patients (7 segments) (32%), the location of dobutamine-induced wall motion abnormalities coincided with the area where exercise-induced hypoperfusion was observed with MIBI., Conclusions: More than a half of syndrome X patients with myocardial perfusion abnormalities also develop regional LV dysfunction during DSE. However, the site of perfusion defects and wall motion abnormalities can be different. Reversible ischemia, defined as a parallel limitation of flow reserve and inducible dysfunction, could be identified as the cause of chest pain in almost one-third of patients.

It is still unclear if performance recovery in postischemic hearts is related to their tissue level of high-energy phosphates before reflow. To test the existence of this link, we monitored performance, metabolism and histological damage in isolated, crystalloid-perfused rat hearts during 20 min of low-flow ischemia (90% coronary flow reduction) and reflow. To prevent interference from different ischemia times and perfusing media compositions, the ischemic ATP level was varied by changing energy demand (electrical pacing at 330 min(-1)). Under full coronary flow conditions, work output, as well as ATP and phosphocreatine contents were the same in control, spontaneously contracting (n = 23) and paced (n = 21) hearts. During low-flow ischemia, the higher work output (p < 0.0001) in paced hearts decreased their tissue content of ATP, phosphocreatine and total adenylates and purines (p < 0.05), as opposed to maintained values in control hearts. During reflow, the recovery of mechanical performance and O2 uptake was 94 +/- 5% and 110 +/- 9% (p = NS vs. baseline) in controls, vs. 71 +/- 5% and 74 +/- 6% in paced hearts (p < 0.004 vs. baseline). The levels of ATP and total adenylates and purines remained constant in control, but were markedly depressed (p < 0.05 vs. baseline) in paced hearts. Phosphocreatine+creatine was the same in both groups. These data, together with the observed lack of creatine kinase leakage and of structural damage, indicate that myocardial recovery during reflow reflects the tissue level of ATP, phosphocreatine and total adenylates and purines during ischemia, regardless of physical cell damage.

Little information is available on the long-term evolution of left ventricular function of medically treated patients with coronary artery disease and gross limitation of coronary flow reserve. The aim of this study was to assess the long-term evolution of effort tolerance and left ventricular function and their relation to the control of ischemic events in patients with coronary artery disease and prolonged inducible exercise-induced myocardial dysfunction who either declined or were ineligible for cardiac revascularization.

We report a complication observed in a 77-year-old man admitted to another hospital for "de novo" angina, in which coronary angiography showed a proximal 65% stenosis of the left anterior descending artery. The patient was medically stabilized, but one month later he developed unstable angina that was not controlled by heparin, nitrate and calcium antagonist infusions. Therefore, he was started on ReoPro (0.25 mg/kg bolus and 10 micrograms/min infusion) but because of persisting symptoms, he was transferred to our unit for urgent PTCA. Angioplasty plus stenting was successful and angina disappeared. The ReoPro infusion was stopped (6 hours after it had been started) for mild oral bleeding. Blood analysis was normal (including platelet count) except for the activated partial thromboplastin (PTT) and prothrombin (PT) time, which exceeded the laboratory limits of determination. Consequently, heparin infusion was also stopped. Eight hours after PTCA, he suddenly developed hypotension, bradycardia and loss of consciousness. The echocardiogram revealed a large pericardial effusion with diastolic collapse of the right cardiac chambers. The patient was treated with volume expanders, plasma and platelet units in an attempt to reestablish a normal hemodynamic pattern and normal platelet function. Elective pericardiocentesis was performed 24 hour later, with drainage of 800 ml of hematic effusion. Severe hemorrhagic complication was induced by ReoPro despite a normal platelet count. This was successfully counteracted with plasma and platelet infusion.

The objective of this study was to test the hypothesis that the beneficial effect of trimetazidine during reflow of ischemic hearts is mediated by energy sparing and ATP pool preservation during ischemia. Isolated rat hearts (controls and rats treated with 10(-6) M trimetazidine, n = 17 per group) underwent the following protocol: baseline perfusion at normal coronary flow (20 minutes), low-flow ischemia at 10% flow (60 minutes), and reflow (20 minutes). We measured contractile function, O2 uptake, lactate release, venous pH and PCO2, and the tissue content of high-energy phosphates and their metabolites. During baseline, trimetazidine induced higher venous pH and lower PCO2 without influencing performance and metabolism. During low-flow ischemia, trimetazidine reduced myocardial performance (P = 0.04) and ATP turnover (P = 0.02). During reflow, trimetazidine improved performance (91 +/- 6% versus. 55 +/- 6% of baseline), prevented the development of diastolic contracture and coronary resistance, and reduced myocardial depletion of adenine nucleotides and purines. ATP turnover during low-flow ischemia was inversely related to recovery of the rate-pressure product (P = 0.002), end-diastolic pressure (P = 0.007), and perfusion pressure (P = 0.05). We conclude that trimetazidine-induced protection of ischemic-reperfused hearts is also mediated by energy sparing during ischemia, which presumably preserves the ATP pool during reflow.

Background: The aim of this study was to assess how coronary flow, oxygen supply and energy demand affect myocardial ATP, phosphocreatine and their metabolites during oxygen shortage and recovery., Methods: Isolated rat hearts were exposed for 20 min to either low-flow ischaemia or hypoxaemia at the same oxygen supply, followed by return to baseline conditions (20 min). Seventy-three hearts were divided into four groups: ischaemic or hypoxaemic, spontaneously beating or paced to increase energy demand., Results: During O2 shortage, myocardial performance was less in ischaemic, spontaneously beating hearts (SpIs), than in the other groups (14 +/- 1% of baseline vs. 25-48%). Consequently, the tissue levels of ATP, total adenylates and phosphocreatine were maintained in SpIs, in contrast to marked decreases in the other groups. Upon reflow, the recovery of performance and of myocardial ATP was 94 +/- 5% in SpIs (P = NS vs. baseline) compared with 64-85% (P < 0.05 vs. baseline) in the other groups. The degree of recovery was positively related to the ischaemic contents of ATP (P = 0.03) and adenylates (P = 0.001), but not to that of phosphocreatine (P = NS)., Conclusion: The maintenance of the ATP pool under low oxygen supply conditions is essential for good recovery. The most important factors that determine the ATP pool size are the energy demand, which increases the formation of diffusible ATP catabolites, and the coronary flow, which removes these catabolites, rather than the oxygen supply per se.

In this paper we show that the engagement of the platelet-endothelial cell adhesion molecule-1 (PECAM-1/CD31) up-regulates the adhesion of human neutrophils to the EA.hy926 endothelial cell line through a phosphoinositide 3-kinase (PI3K)-dependent pathway. Indeed, LY294002 and wortmannin prevented the effect of PECAM-1/CD31 cross-linking on cell adhesion, at concentrations known to inhibit PI3K without affecting other kinases. Both compounds blocked neutrophil binding to murine fibroblasts transfected with human ICAM-1, to purified ICAM-1 protein, or to fibronectin, suggesting that PECAM-1/CD31-mediated up-regulation of beta2 and beta1 integrin-mediated adhesion is PI3K-sensitive. We also provide evidence for the association of PECAM-1/CD31 to PI3K, because PI3K was detectable in neutrophil lysates after PECAM-1/CD31 cross-linking and immunoprecipitation. PECAM-1/CD31-dependent recruitment of PI3K was suggested by the finding that the serine/threonine kinase p70 S6 kinase (S6K), a signaling protein downstream of PI3K, is activated in neutrophils upon PECAM-1/CD31 cross-linking, based on the appearance of serine phosphorylation in S6K immunoprecipitates. In turn, S6K is not directly involved in the up-regulation of integrin function because rapamycin, which can inhibit S6K independent of PI3K, did not block PECAM-1/CD31-induced adhesion of neutrophils to beta1 and beta2 integrin substrates. In conclusion, PECAM-1/CD31 appears to be one of the molecules functionally coupled to PI3K, suggesting that this enzyme may represent a common pathway of integrin and adhesiveness regulation in leukocytes.

We studied 15 patients with chronic coronary artery disease (13 men aged 62 +/- 8 years) undergoing dobutamine (5 to 40 microg/kg/min) echocardiography at the end of two 15-day treatment periods with placebo and trimetazidine (20 mg 3 times daily) given in random order, according to a double-blind, crossover design. Results show that trimetazidine improves resting left ventricular function and reduces the severity of dobutamine-induced ischemic myocardial dysfunction.

We studied the relationship between coronary anatomy, perfusion and metabolism in myocardial segments exhibiting transient and persistent perfusion defects on stress/rest 99Tcm-MIBI single photon emission tomography in 35 patients (31 males, 4 females, mean age 56 +/- 7 years) with a previous myocardial infarction. Quantitative coronary angiography and assessment of myocardial perfusion reserve and glucose metabolism were performed within 1 week of one another. Perfusion was assessed by SPET after the intravenous injection of 740 MBq of 99Tcm-MIBI at rest and after exercise. Regional myocardial glucose metabolism was assessed by position emission tomography at rest (200 MBq of 18F-2-deoxyglucose, FDG) after an overnight fast with no glucose loading. All 35 patients exhibited persistent perfusion defects consistent with the clinically identified infarct site, and 27 (77%) also showed various degrees of within-infarct FDG uptake; 11 patients developed exercise-induced transient perfusion defects within, or in the vicinity of, 15 infarct segments and resting FDG uptake was present in 10 of these segments (67%). Five patients also showed exercise-induced transient perfusion defects in nine segments remote from the site of infarct: resting FDG uptake was present in six of these regions (67%). Finally, nine patients had increased glucose uptake in non-infarcted regions not showing transient perfusion defects upon exercise testing and perfused by coronary arteries with only minor irregularities. Our results confirm the presence of viable tissue in a large proportion of infarct sites. Moreover, FDG uptake can be seen in regions perfused by coronary arteries showing minor irregularities, not necessarily resulting in detectable transient perfusion defects on a MIBI stress scan. Since the clinical significance of such findings is not clear, further studies should be conducted to assess the long-term evolution of perfusion, function and metabolism in non-revascularized patients of those remote areas which are apparently normally perfused, but show abnormal fasting FDG uptake after myocardial infarction. Such studies may have important implications for the management of post-infarct patients, as the preservation of coronary vasodilator reserve and myocardial metabolism in remote myocardium may be seen as an additional goal in the treatment of such patients.

Aims: Betablockers are very effective in patients with angina and angiographically smooth coronary arteries (syndrome X), but may exacerbate the state of insulin resistance that is known to be present in such patients. The aim of the study was to evaluate the effects of short-term treatment with atenolol on carbohydrate metabolism in syndrome X patients, as compared to normal subjects., Methods and Results: Seventeen patients (15 females, 55 +/- 8 years, BMI 23.4 +/- 2.7 kg/m2) and 11 controls (5 females, 50 +/- 7 years, BMI 23.1 +/- 2.0 kg/m2) were studied twice by an intravenous glucose tolerance test (IVGTT, 0.5 g/kg) after ten days of both placebo and atenolol (100 mg o.d.), given in random order. Metabolic indices measuring glucose effectiveness and insulin sensitivity were derived from minimal model analysis of the glucose and insulin profiles measured during the IVGTT. Indices of first- and second-phase insulin release were also calculated from the IVGTT insulin response. Atenolol had different metabolic effects on normal subjects and syndrome X patients. Despite the fact that the drug was found to be effective in relieving symptoms of chest pain, it induced a significant (p < 0.05) worsening of insulin resistance in syndrome X patients. No such effect was observed in control subjects. On the other hand, atenolol produced a marked reduction (40%, p < 0.05) of first-phase insulin release in control subjects, but no significant change of the same index in syndrome X patients., Conclusion: These results show that betablockers are very effective for controlling symptoms and improving quality of life in syndrome X patients. However, they appear to further impair the ability to dispose glucose. Long-term studies on the net effects of beta-blockade administration for the treatment of such patients are warranted.

The authors report a case of septal panniculitis induced by atenolol in a patient with coronary artery disease. Several tender, erythematous, suppurated subcutaneous nodules appeared over the metacarpal-phalanx and interphalanx joints of both hands. Hematology indicated a transient inflammatory immunomediated disorder, with an increase of cytotoxic suppressor lymphocytes and presence of antinuclear antibodies. The dramatic inflammatory involvement of the subcutaneous connective tissue could have eventually progressed toward fibrosis, if atenolol had not been withdrawn. This raises the possibility that retroperitoneal fibrosis, a recognized adverse effect of beta blockers, may just represent the terminal phase of undetected connective tissue inflammation occurring in districts not easily explorable before overt manifestations of the disease. Since retroperitoneal fibrosis has already been associated with migratory panniculitis and described as mesenteric panniculitis, it is tempting to speculate that these manifestations originate from the same mechanisms.

In order to assess the diagnostic accuracy of stress/rest myocardial perfusion scintigraphy in the follow-up of patients undergoing percutaneous transluminal coronary angioplasty (PTCA) we studied 50 patients (pts) before and 6 months after PTCA. All patients underwent control coronary angiography and then were divided in 2 groups, according to angiographic evidence of restenosis (25 pts) or no restenosis (25 pts). Myocardial perfusion imaging was performed with 99mTc-methoxy-isobutyl-isonitrile (MIBI). For MIBI scans, both qualitative and semi-quantitative analysis were performed. SPECT images were displayed on a color monitor in random order and graded blindly by 2 experienced observers. Rest and stress MIBI uptake was scored using a 4-point scale (ranging from 0 = normal, to 3 = absence of uptake). Individual subjects' perfusion scores were calculated by adding the individual segments' scores. History of relapsing angina showed a sensitivity and specificity of 76 and 96%, respectively. Exercise testing and MIBI tomoscintigraphy exhibited sensitivity and specificity of 80 and 56%, and 92 and 44%, respectively. However, when considering semiquantitative data and comparing them with pre-PTCA studies, specificity of MIBI scan increased to 96%, while sensitivity decreased to 72%. The results of the present study confirm high sensitivity and low specificity for both exercise ECG and myocardial perfusion scintigraphy, in the detection of restenosis following PTCA. However, when performing semiquantitative analysis of perfusion scanning and comparison with pre-PTCA images, the specificity of MIBI tomoscintigraphy increases significantly. Therefore, when adopting myocardial perfusion scintigraphy for the follow-up of patients undergoing PTCA, a pre-revascularization scan should be obtained as often as possible. This approach, in the context of a positive test, makes feasible the assessment of often partial improvements in perfusion of the myocardium relative to the treated vessel, consequently avoiding many false positive results which invariably lead to coronary angiography.

Aims: We investigated the ability of T-wave pseudonormalization and ST-segment elevation, which are demonstrated in infarct-related leads during submaximal exercise testing, to predict late recovery of contractile function., Methods: We studied 88 consecutive patients (73 males, mean age 59 +/- 8 years) with anterior infarction, persistent T-wave inversion and a documented lesion of the proximal segment of the left anterior descending coronary artery. They all underwent 2D-echocardiography on admission, 4 weeks as well as 6 months after myocardial infarction to evaluate the dysfunction score and the ejection fraction. Submaximal (75% of maximal predicted heart rate) exercise testing was performed in 80 patients 2 weeks after myocardial infarction following discontinuation of treatment., Results: During exercise testing, 59 of the 88 patients showing negative T-waves on the resting electrocardiogram exhibited pseudonormalization (group A) in at least three adjacent precordial leads, whilst 29 (group B) did not. Patients of group A more frequently exhibited an early creatine kinase peak (41% vs 24%, P < 0.05) and residual angiographic perfusion (97% vs 69%, P < 0.05). The dysfunction score did not change in group B (from 19 +/- 7 to 22 +/- 4), but decreased in group A (from 18 +/- 4 to 11 +/- 6 P < 0.05). The ejection fraction was similar in the two groups on admission (group A: 48 +/- 7%, group B: 45 +/- 10%), but was significantly different at 4-week (52 +/- 99 vs 42 +/- 11%, P < 0.05) and 6-month follow-up (58 +/- 9 vs 44 +/- 10%, P < 0.01). The concomitant presence of ST-segment elevation and T-wave normalization showed the highest positive predictive value for left ventricular function recovery (100%)., Conclusions: T-wave normalization induced by submaximal exercise test is frequently associated with residual perfusion to the infarct area and predicts progressive improvement in regional wall motion, especially if associated with ST-segment elevation. Therefore, these electrocardiographic findings may be used as easily obtainable markers of residual viability that predict late recovery in contractile function.

Objectives: This study reports the first multicenter experience with the Wiktor coil stent for treatment of chronic total coronary artery occlusions (CTOs)., Background: Percutaneous transluminal coronary angioplasty (PTCA) of CTO is associated with very high restenosis and reocclusion rates. Coronary stenting has been proposed as a means of improving outcome. However, the Wiktor device for CTOs has never been tested in a large patient sample., Methods: From January 1993 to December 1996, 89 patients with 91 CTOs underwent Wiktor stent implantation after successful PTCA. The post-stenting regimen consisted of warfarin (Coumadin) plus aspirin in the initial 49 patients (55%) and aspirin plus ticlopidine in 40 patients (45%)., Results: Stenting was successful in 87 patients (98%). At 1 month, 6% of patients had subacute stent thrombosis, 3% had a major bleeding event, and 1% had access-site complications. Subacute stent thrombosis showed univariate association with warfarin therapy (p = 0.009). Angiographic follow-up was obtained in 76 (93%) of 82 eligible patients. The restenosis rate was 32%, including 4% reocclusions. By multiple logistic regression analysis, restenosis was independently associated with multiple stents (adjusted odds ratio [OR] 27.67, 95% confidence interval [CI] 4.25 to 79.95, p = 0.0008) and increasing values of occlusion length (adjusted OR 1.23, 95% CI 1.09 to 1.39, p = 0.001). Freedom from death, myocardial infarction or stented vessel revascularization was 87% and 72% at 1 and 3 years, respectively., Conclusions: Short- and long-term clinical and angiographic outcomes are favorable in patients undergoing Wiktor stent implantation in CTO. Further technical improvement is needed to reduce the restenosis rate in patients with long lesions and multiple stents.

The present study was designed to test the hypothesis that patients with angina, positive exercise test and angiographically smooth coronary arteries (syndrome X), may exhibit abnormal myocardial glucose handling, as assessed by fluorodeoxyglucose (FDG) and positron emission tomography (PET) and to investigate the possibility that this abnormality could be reversed by treatment with betablockers, the drugs of choice in most patients with syndrome X. Eight consecutive patients (4 females, age 53 +/- 4 yrs) with syndrome X were studied. Off therapy, they underwent stress/rest 99m-TcMIBI SPET (360 degrees) and assessment of resting glucose metabolism by PET. PET studies were again performed after a 10 day treatment period on oral atenolol (100 mg/o.d.). All patients exhibited significant fasting FDG uptake in 2 or more myocardial regions. Overall, there were 28 of 48 segments (58%) with abnormal tracer uptake. On atenolol, there were only 5 segments with persistent FDG uptake (10%) in 2 patients. At rest, 7 patients exhibited perfusion defects in 14 myocardial segments. With stress performed in pharmacological wash-out, 5 patients developed perfusion defects in 10 myocardial segments. Eight of these segments were already underperfused at rest, and showed further reduction in perfusion after stress. All hypoperfused segments showed abnormal FDG uptake when the PET study was performed off therapy. The results suggest that, in patients with syndrome X, imbalance of the demand/supply ratio, either caused by limited coronary flow reserve or by primary vasoconstriction with reduction in myocardial perfusion, may determine a sustained metabolic shift towards anaerobic glycolysis. The mechanism by which atenolol improves metabolism in these patients could be simply related to reduction in O2 consumption.

Previous studies have shown that adhesion molecules play a crucial role in leukocyte-endothelium interactions that occur during myocardial ischemia and reperfusion. We assessed the plasma levels of the soluble form of E-selectin (sE-selectin) and intercellular adhesion molecule-1 (sICAM-1) in 15 patients with acute myocardial infarction (AMI) and in 15 controls with chronic stable angina. In patients with AMI, the levels of sE-selectin and sICAM-1 increased significantly during the first 8 h after infarction and subsequently decreased. Soluble E-selectin levels were inversely related to the peak plasma levels of creatine kinase-MB (CK-MB), and the time course of their appearance in plasma correlated with that of neutrophil count and plasma D-dimer. In individual patients, peak and mean sICAM-1 levels correlated respectively with plasma D-dimer concentrations and monocyte count, but no correlation were found when their time courses were analyzed. Eight hours after symptom onset, the mean plasma sE-selectin levels were higher in patients with AMI than in those with stable angina, whereas no significant differences were found in mean plasma sICAM-1 levels between the two groups at every time analyzed. In the acute phase of MI (a) sE-selectin and sICAM-1 levels increase during the first 8 h and subsequently decrease; (b) the increase in sE-selectin probably reflects activation of endothelial cells, correlates with other inflammatory and coagulation parameters, and is inversely related to the degree of myocardial damage; and (c) sICAM-1 plasma levels do not represent a good marker of "cell activation" because they reflect activation of different cells and may be affected by different conditions.

Increased sympathetic drive in symptomatic menopausal women was reduced after estrogen replacement therapy for 4 months, which has a potentially beneficial effect on cardiovascular functions.

Atenolol reduces QT dispersion and corrected QT interval in patients with syndrome X. This suggests that symptomatic improvement induced by atenolol in syndrome X patients may be partly related to reduction in abnormally augmented sympathetic tone.

Acute administration of estradiol 17beta increases aortic blood flow velocity in menopausal women. This suggests that the effect of the ovarian hormone on cardiac dynamics is mainly dependent on a reduction in peripheral vascular resistances.

Background: Percutaneous transluminal coronary angioplasty (PTCA) of chronic total coronary artery occlusions is associated with very high restenosis and reocclusion rates. Coronary stenting has been proposed as a means of improving outcome. However, the Wiktor device for chronic coronary occlusion has never been tested in a large patient sample. This study reports the first multicenter experience with the Wiktor stent for treatment of chronic occlusions., Methods: From January 1993 to December 1996, 89 consecutive patients with 91 chronic occlusions underwent Wiktor stent implantation after successful PTCA. Post-stenting regimen consisted of coumadin plus aspirin in the first 49 (55%) patients and aspirin plus ticlopidine in the following 40 (45%)., Results: Stenting was successful in 87 (98%) patients. At 1 month, 6% of patients had subacute stent thrombosis, 1% access-site complications and 3% major bleeding events. Stent thrombosis showed a univariate association with coumadin therapy (p = 0.009). Angiographic follow-up was obtained in 93% of 82 eligible patients. Restenosis rate was 32%, including 4% reocclusions. Through multiple logistic regression analysis, restenosis was independently associated with multiple stents (odds ratio-OR = 27.67, 95% confidence interval-CI = 4.25 to 79.95, p = 0.0008) and increasing values of occlusion length (OR = 1.23, 95% CI = 1.09 to 1.39, p = 0.001). Freedom from death, myocardial infarction or stented vessel revascularization was 87 and 72% at one and three years, respectively., Conclusions: Short- and long-term clinical and angiographic outcomes are favorable in patients undergoing Wiktor stent implantation for chronic coronary occlusion. Further technical refinements are needed to reduce restenosis rate in patients with long lesions and multiple stents.

Palpitation is an unpleasant awareness of an abnormal beating of the heart. This symptom may be brought on by a variety of cardiac disorders, such as cardiomyopathy, valvular heart disease, and coronary artery disease, but the most common cause is primary cardiac arrhythmias. Several noncardiac disorders may also cause palpitations, and in this case are an effect of the disease upon cardiac rhythm. Palpitations occur frequently in women at all ages, especially during the luteal phase of the menstrual cycle, during pregnancy, and during the perimenopausal period. Palpitations occurring at young age and associated with fast heart rate are frequently due to Wolff-Parkinson-White syndrome or other forms of re-entrant tachycardia, and may require catheter ablation. A correlation between ovarian hormones and occurrence of paroxysmal supraventricular tachycardia has recently been reported in female patients with normal menstrual cycles; palpitations are frequently reported in cases of mitral valve prolapse, whereas episodes of paroxysmal supraventricular tachycardia reported during pregnancy may be due to mechanical stimuli or to a suggested arrhythmogenic effect of pregnancy. Palpitations during the perimenopausal period are usually benign and seem to be related to the increased sympathetic activity caused by the menopause. Although the vast majority of palpitations are benign and need not be treated, an electrophysiological study is indicated for those patients who have a documented episode of palpitation associated with syncope or with a pulse that is inappropriately rapid during symptoms. The treatment of palpitations due to cardiac arrhythmias is dependent upon the kind of arrhythmia detected during either invasive or noninvasive electrophysiological studies.