Antiplatelet effects of angiotensin-converting enzyme inhibitors compared with aspirin and clopidogrel: a pilot study with whole-blood aggregometry

Background Although specific antiplatelet drugs are well-established and effective in atherosclerosis prevention, recent clinical trials have also shown that use of angiotensin-converting enzyme (ACE) inhibitors results in a decrease in cardiovascular events. Therefore, in this study, we sought to assess the coagulative activity of patients with cardiovascular disease grouped for treatment with either ACE inhibitors, aspirin, clopidogrel/aspirin, or none of these medications. Methods Blood samples from 303 patients with cardiovascular disease were analyzed with whole-blood aggregometry. Platelet aggregation was determined by the increase in impedance across paired electrodes in response to the aggregatory agents adenosine diphosphate (ADP) or collagen. Results As the central finding, platelet aggregation was attenuated by ACE inhibitors and by aspirin or clopidogrel/aspirin, which was indicated by a lower impedance increase compared with no medication. With ACE inhibition, platelet aggregation decreased by 33% (P = .042) after ADP induction. No significant antithrombotic effect was seen with aspirin alone (17%, P = 1.0), whereas a decrease in ADP-induced platelet aggregation was extensive with clopidogrel/aspirin (85%, P = .001). After collagen induction, platelet aggregation was reduced by 16% (P = .028) in the presence of ACE inhibitor therapy, whereas inhibition with aspirin and clopidogrel/aspirin was 23% (P = .004) and 35% (P = .026), respectively, compared with participants who were not treated. Conclusions These ex vivo data on whole-blood aggregometry provide direct evidence that ACE inhibitors decrease platelet aggregation, whereas aspirin and clopidogrel are confirmed as established antithrombotics. Pleiotropic effects of ACE inhibition on platelet function may contribute to the clinical benefit observed with this drug class on major cardiovascular end points. (Am Heart J 2003;145:343-8.)     

Serum glucose and lipid levels in adult congenital heart disease patients

Atherosclerosis has been correlated with known cardiovascular risk factors such as serum glucose or lipid levels. Because congenital heart disease patients tend to survive until adulthood, atherosclerosis has also become a matter of concern in these patients. One hundred fifty-eight congenital heart disease patients and 152 patients selected at random from the population were studied and compared to determine serum glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, and triglycerides levels. Both groups had similar socioeconomic status levels and the same environmental influences. Significant differences were seen between congenital heart disease patients and the control group, after sex, age, and body mass index adjustment, in fasting plasma glucose (97.7 [94.2-101.2] vs 86.9 [83.2-90.7], P < .001), total cholesterol (171.5 [165.7-177.3] vs 199.8 [90.7-206.0], P < .001), LDL cholesterol (103.9 [98.8-108.8] vs 123.8 [118.5-129.1], P < .001), and high-density lipoprotein cholesterol (48.1 [46.2-50.0] vs 54.2 [52.1-56.2], P < .001) levels. Nonsignificant differences were seen in triglycerides concentrations. Those patients with ventricular septal defect, coarctation of the aorta, and cyanosis had the lowest total cholesterol and LDL cholesterol concentrations. Congenital heart disease patients have lower plasma cholesterol concentrations and higher serum glucose levels than noncongenital ones.     

Double-blind comparison between zofenopril and lisinopril in patients with acute myocardial infarction: results of the Survival of Myocardial Infarction Long-term Evaluation-2 (SMILE-2) study

Background Angiotensin-converting enzyme (ACE) inhibitors have been reported to be effective in placebo-controlled trials in various subsets of patients with acute myocardial infarction (MI). However, no direct comparisons have been performed between different ACE inhibitors in the same patient population.Methods This phase III, double-blind, parallel-group, multicenter study compared the safety and efficacy of zofenopril and lisinopril in 1024 thrombolyzed patients with acute MI. Patients, aged 18 to 75 years, were randomized to receive oral zofenopril (30-60 mg/day) or lisinopril (5-10 mg/day), starting within 12 hours of completion of thrombolytic therapy and continuing for 42 days. The primary study end point was the incidence of severe hypotension (systolic blood pressure <90 mm Hg), either cumulative or drug-related. Secondary end points included additional safety and efficacy parameters.Results The overall incidence of severe hypotension was slightly 5more reduced with zofenopril (10.9%) than with lisinopril (11.7%, P = .38). The incidence of drug-related severe hypotension was slightly but significantly lower with zofenopril than with lisinopril (6.7 vs 9.8%, 2-tailed P = .048). The 6-week mortality rate was 3.2% in the zofenopril group and 4.0% in the lisinopril group (P = .38), and no significant differences were observed in the incidence of major cardiovascular complications or any safety variables between the 2 ACE inhibitors.Conclusions The SMILE-2 study demonstrates that both zofenopril and lisinopril are safe and associated with a rather low rate of severe hypotension when given in accordance with a dose-titrated scheme to thrombolyzed patients with acute MI. These findings could have a positive clinical impact and increase the proportion of patients with acute MI who can be safely treated with ACE inhibitors. (Am Heart J 2003;145:80-7.)     

Associations between angiotensinogen gene variants and left ventricular mass and function in the HyperGEN study

Background The angiotensinogen M235T polymorphism is positively associated with plasma angiotensinogen, hypertension, and coronary heart disease. However, the association of M235T polymorphism with left ventricular (LV) mass and function is not well defined at the population level. We investigated whether 2 tightly linked polymorphisms of angiotensinogen gene, M235T and G-6A, are associated with LV mass and function in a large population-based sample, composed mostly of patients with hypertension. Methods Two-dimensional guided M-mode and pulsed Doppler scan echocardiograms were performed in 605 participants. The angiotensinogen M235T was analyzed with a standard polymerase chain reaction test, and the G-6A variant was measured with mass spectrophotometry. Results The association of angiotensinogen gene to LV mass and LV mass indexed to body surface area (LVMI) differed significantly between subjects with normotensive and hypertensive conditions with respect to the direction of association (P < .005). The methionine-threonine/threonine-threonine genotype was negatively associated with LV mass and LVMI in patients with hypertension after adjustment for blood pressure, antihypertensive medication use, weight, and other covariates (P < .001), and patients with normotensive conditions with the methionine-threonine/threonine-threonine genotype had higher LV mass and LVMI (P = .04, for LV mass; P = .14, for LVMI). The association in patients with normotensive conditions was not influenced by blood pressure but was partly confounded by weight. Conclusion Variation in the angiotensinogen gene was modestly associated with LV mass independently of covariates in patients with hypertensive conditions. The direction of the association was opposite to that observed in patients with normotensive conditions, probably because of the influence of other risk factors or antihypertensive medication use or both. (Am Heart J 2002;143:854-60.)     

Symptom presentation of acute myocardial infarction: influence of sex,age, and risk factors

Objectives The purpose of this study was to examine the symptomatology of onset of acute myocardial infarction (AMI) in patients according to sex, age, and existence of conventional risk factors. Background Some studies have suggested that sex and other patient characteristics may influence symptoms in AMI, but data were limited and conflicting. Methods This was a prospective, observational study of a large number of symptoms in 1996 patients admitted to Clinical Hospital Split between January 1990 and July 1995 as the result of a first AMI. For each patient, the structured data form covering experience of pain at 10 body locations and 11 other symptoms, baseline characteristics, risk factors, and peak cardiac enzyme levels was completed a median of 3 days after AMI. Results Any pain, and specifically chest pain, was more often reported by male patients, smokers, hypertensive patients, nondiabetic patients, and hypercholesterolemic patients. Women were more likely to report nonchest pain other than epigastric and right shoulder pain, as well as various nonpain symptoms. The independent predictors of atypical AMI presentation (ie, absence of pain) in both men and women were lower levels of creatine kinase-MB fraction (P < .0001 and P = .0003, respectively), diabetes mellitus (P = .0002 and P = .002, respectively), older age (P = .001 and P = .01, respectively), and absence of smoking in men (P = .005). The independent predictors of presence of nonpain symptoms in both men and women were higher levels of creatine kinase-MB fraction (P = .01 and P = .049, respectively) and diabetes mellitus (P = .048 and P = .005, respectively); in men, it was hypercholesterolemia (P = .01). Conclusions Our results suggest that sex, age, smoking, hypertension, diabetes, and hypercholesterolemia may affect the symptoms in AMI. Women with diabetes represent a high-risk subgroup for painless onset followed by various other symptoms. (Am Heart J 2002;144:1012-7.)     

Septal wall thinning and systolic dysfunction in patients with hypertrophic cardiomyopathy caused by a cardiac troponin I gene mutation

Background Lysine 183 deletion in the cardiac troponin I gene is 1 of the mutations that causes hypertrophic cardiomyopathy (HCM). However, the clinical course and determinants of poor prognosis in patients with this mutation have not been well established. Methods and Results We analyzed 10 probands with HCM caused by this mutation and their family members. Forty-six of these 79 subjects were found to be carriers, and 33 were non-carriers. All non-carriers had a percent fractional shortening (%FS) of >25% at all ages. By contrast, 7 of 24 carriers >40 years of age had a %FS of <25%, and no carriers <40 years of age had a %FS of <25%. The change in interventricular septal thickness and the change in %FS were significantly correlated (R = 0.758; P = .0017). Conclusion These results suggest that about 30% of patients with HCM caused by a lysine 183 deletion mutation in the cardiac troponin I gene have systolic dysfunction develop after 40 years of age, and that patients with this mutation whose interventricular septal thickness shows a serial decrease should be followed-up closely for development of systolic dysfunction. (Am Heart J 2002;143:690-5.)     

A new thrombolytic agent,monteplase, is independent of the plasminogen activator inhibitor in patients with acute myocardial infarction: initial results of the COmbining Monteplase with Angioplasty (COMA) trial

Background Both thrombolytic therapy and coronary angioplasty have been inconsistent together for primary acute myocardial infarction (AMI) therapy, because conventional thrombolytic agents accelerate plasminogen activator inhibitor-1 (PAI-1) activity. However, combining newly developed mutant tissue-type plasminogen activators with coronary angioplasty should be reconsidered. Methods This study was designed to investigate clinical usefulness of such an agent, monteplase, for treatment of AMI in light of PAI-1 kinetics. One hundred fifty-four consecutive patients with AMI were randomly assigned to receive direct coronary angioplasty (Group I) or coronary angioplasty after pretreatment with intravenous monteplase (Group II). In 90 of these patients, total PAI-1 antigen levels were serially measured. Results Baseline PAI-1 levels at admission were higher in patients with occluded infarct-related arteries than in patients with patent arteries in Group I (39 ± 4 vs 20 ± 2 ng/mL, P < .01) and in Group II (36 ± 3 vs 27 ± 2 ng/mL, P < .05). In the high PAI-1 level subgroup (≥27 ng/mL, n = 53), Group II showed a higher patency rate than Group I (56 vs 18%, P < .01). Multiple logistic regression analysis indicated that patency could be predicted by the PAI-1 level in Group I (Wald χ²= 3.94, P = .02, odds ratio 0.924, 95% CI 0.855-0.999), but not in Group II. Serial change patterns in the PAI-1 level were identical in Group I and Group II. Conclusion Because monteplase can be used independently of PAI-1 kinetics, a combination of monteplase administration at a community hospital with prompt transfer to a tertiary center for coronary intervention may be a powerful strategy for AMI. (Am Heart J 2002;144:e5.)     

Potential thrombophilic mutations/polymorphisms in patients with no flow-limiting stenosis after myocardial infarction

Background Although inherited thrombophilias are more common in patients with venous thromboembolism, their influence on the development of myocardial infarction (MI) requires clarification.Methods and Results To determine whether there are increased frequencies of mutations/polymorphisms in 14 genes potentially causing thrombophilia in patients with no flow-limiting stenoses after MI compared with patients with ≥1 flow-limiting stenosis of >50%, we studied 395 patients (60 with no flow-limiting stenosis) who underwent angiography at approximately 1 month. The mutations/polymorphisms studied included Factor V Leiden, prothrombin variant G20210A, β-fibrinogen 448 (G/A), endothelial protein C receptor (23-base pair insertion), methyl tetrahydrofolate reductase 677 (C/T), platelet glycoprotein IIIa PlA1/A2, plasminogen activator inhibitor-1 4G/5G, angiotensin II type 1 receptor (A/C), hemochromatosis gene 282 (G/A), nitric oxide synthase (NOS) (3 forms: eNOS, eNOS3, eNOS4), p22 phox of NADPH oxidase C242T, and angiotensin-converting enzyme insertion/deletion polymorphism. The frequencies of Factor V Leiden and the β-fibrinogen 448 A allele were higher in patients with no flow-limiting stenosis than in patients with ≥1 stenosis (11.7% vs 3.6%, odds ratio [OR] 3.6, 95% CI 1.3-9.4, P = .015; and 42% vs 27%, OR 2.0, 95% CI 1.1-3.5, P = .018, respectively), and there was a trend toward an increased frequency of prothrombin variant G20210A (6.7% vs 2.1%, OR 3.4, 95% CI 0.95-11.8, P = .069). However, in patients with no flow-limiting stenosis after MI the frequencies of the other gene mutations/polymorphisms were not increased. Also, there were no significant interactions between any of these 14 mutation/polymorphisms, major cardiovascular risk factors, and the absence of any flow-limiting stenosis, except for Factor V Leiden and hypertension (OR 6.34, 95% CI 2.67-100, P = .004).Conclusions Patients with no flow-limiting stenosis after MI had increased frequencies of 2 inherited thrombophilias (Factor V Leiden and β-fibrinogen 448 A allele), and there was a trend toward an increased frequency of prothrombin variant G20210A compared with patients with ≥1 stenosis. These data suggest that polymorphisms/mutations in some gene products influencing coagulation may influence the pathogenesis of MI. (Am Heart J 2003;145:118-24.)     

Elevated soluble P-selectin levels are associated with an increased risk of early adverse events in patients with presumed myocardial ischemia

Background Cell adhesion molecules (CAMs) play a pivotal role in the interactions between leukocytes, platelets, and vascular endothelium. Soluble CAMs (sCAMs) are shed from cell surfaces and reflect cellular activation. Elevated levels of sCAMs have been reported in the acute coronary syndromes. We hypothesized, therefore, that sCAMs might prove of prognostic value in patients with acute chest pain presumed to be the result of myocardial ischemia. Methods One hundred twenty-six consecutive patients with chest pain, thought clinically to represent myocardial ischemia, were studied prospectively. Soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin) and P-selectin (sP-selectin) levels were assayed at presentation, as were cardiac troponin I (cTnI) and creatine kinase-MB_mass (CK-MB_mass). The primary study end point was the occurrence of a serious cardiac event (SCE) during the index admission or the subsequent 3 months. Results sP-selectin and cTnI levels were significantly higher among patients who had an early SCE (P = .006 and P < .001, respectively). Both remained independently predictive (P < .001) in a multivariate regression equation. The other independent predictor was a history of vascular disease (P < .05). No other markers were significant predictors of early outcome. Conclusion Elevated sP-selectin levels, but not those of other sCAMs, are predictors of early adverse events in patients with chest pain presumed caused by myocardial ischemia. Their utility in predicting the outcome of individual patients is, however, limited. (Am Heart J 2002;143:235-41.)     

Diabetes mellitus is associated with a shift in the temporal risk profile of inhospital death after percutaneous coronary intervention: an analysis of 25,223 patients over 20 years

Background Numerous studies have demonstrated that patients with diabetes have higher rates of restenosis, late myocardial infarction, and late death after percutaneous coronary interventions (PCI). However, it remains unclear whether patients with diabetes mellitus also have an increased hazard for early death after either elective or urgent PCI. Methods Patients undergoing PCI at the Mid American Heart Institute between 1980 and 1999 were identified. The main end point was inhospital death. Patients were stratified both by diabetes status and whether they underwent elective or urgent PCI. Results There were 17,341 nondiabetic patients and 4308 patients with diabetes who underwent elective PCI. There were 2946 nondiabetic patients and 628 patients with diabetes who underwent urgent PCI. Multivariate analysis demonstrated that diabetes was associated with increased inhospital mortality rate after any PCI (odds ratio 1.4, 95% CI 1.1-1.8, P = .003). The unadjusted inhospital mortality rates for the nondiabetic patients and patients with diabetes were 0.8% and 1.4%, respectively (P < .001), after elective PCI. The mortality rate was 6.9% for the nondiabetic patients and 12.7% for the patients with diabetes (P < .001) after urgent PCI. The inhospital mortality rates among diabetic patients appear to be decreasing over time among the elective cohort (elective PCI diabetes-time interaction, P = .007) but not in the urgent cohort (urgent PCI-diabetes-time interaction, P = .68). Conclusions There has been an improvement in the inhospital survival rate among patients with diabetes in the elective PCI cohort. This improved hospital survival has yet to be realized among patients with diabetes undergoing urgent PCI. (Am Heart J 2003;145:270-7.)     

Implantation of CD133 Stem Cells in Patients Undergoing Coronary Bypass Surgery: IMPACT-CABG Pilot Trial

Background

The Implantation of Autologous CD133⁺ Stem Cells in Patients Undergoing CABG (IMPACT-CABG) trial is investigating the feasibility, safety, and efficacy of intramyocardial injections of autologous CD133⁺ stem cells during coronary artery bypass grafting (CABG) in patients with chronic ischemic cardiomyopathy. We are reporting the results of the first 5 open-label patients.

Methods

Bone marrow was harvested from iliac crests and stem cells were isolated using the CliniMACS CD133⁺ Reagent System (Miltenyi Biotec, GmbH, Bergisch Gladbach, Germany). Patients received CABG, followed by CD133⁺ cellular injection in the revascularized hypokinetic myocardium.

Results

Five males New York Heart Association (NYHA) class III patients aged 64 ± 10 years were treated. Immunomagnetic cell processing allowed an average of 100 ± 48-fold enrichment in CD133⁺ cells, with 92 ± 11% recovery after selection. Mean number of CD133⁺ cells injected was 8.4 ± 1.2 million. There were no protocol-related complications during the 18-month follow-up and all patients improved to NYHA class I. Six-month echocardiography showed no significant improvement in left ventricular ejection fraction (34 ± 2% at baseline vs 38 ± 12%: P = 0.50). However, cardiac magnetic resonance showed that systolic wall thickening increased from 15.0 ± 10.5% to 29.0 ± 22.1% (P = 0.01). In addition, mean segmental wall thickness also improved in comparison with baseline (10.7 ± 2.7% to 12.1 ± 4.8%; P < 0.01).

Conclusions

This work represents the first Canadian experience with CD133⁺ stem cells for the treatment of chronic ischemic cardiomyopathy. These results demonstrate the initial safety and feasibility of the IMPACT-CABG pilot trial. Subsequent patients are now being randomized to receive either CD133⁺ stem cell or placebo.     

Effect of atorvastatin and pravastatin on serum C-reactive protein

Background Extra-lipid effects of statins, such as anti-inflammatory actions, may contribute to their clinical benefit. These effects, with important implications for the concept of a statin “class effect,” may be drug specific or may be related to the extent of lipid lowering. Methods We randomized 130 patients to treatment with either atorvastatin (80 mg daily, n = 63) or pravastatin (40 mg daily, n = 67), and measured serum lipids, C-reactive protein, and fibrinogen at baseline and after 3 months of therapy. Results Mean C-reactive protein (CRP) levels were significantly reduced in both groups, with a 36% reduction in the atorvastatin group (0.39 ± 0.36 to 0.25 ± 0.27, P = .001) and a 22% reduction observed in the pravastatin group (0.40 ± 0.33 to 0.31 ± 0.32, P = .003). A reduced or unchanged CRP level was seen in 67.2% of pravastatin-treated patients (45/67) and 73% of atorvastatin- treated patients (46/63) (P = .47). There was no difference between drugs in either the absolute or relative reductions in CRP levels. However, whereas the reduction of CRP with pravastatin was unrelated to the degree of low-density lipoprotein reduction (r = −.05, P = .69), atorvastatin-induced CRP reductions correlated directly to the change in low-density lipoprotein-C (r = .33, P = .009). Conclusions High-dose atorvastatin and pravastatin both reduce CRP levels. However, whereas pravastatin's effect on CRP is independent of lipid-lowering efficacy, these data suggest that lipid-dependent mechanisms are, at least in part, active in atorvastatin-treated patients. (Am Heart J 2003;145:e8.)     

Perceptions of chest pain differ by race

Background African American patients are less likely to receive thrombolytic therapy and coronary revascularization than are white patients. Delay and clinical presentation may be keys to understanding differences in care. Objective To determine how symptom recognition and perception influence clinical presentation as a function of race, we characterized symptoms and care-seeking behavior in African American and white patients seen in the ED with chest pain. Methods The prospective study was conducted from April 1999 to September 1999 among patients who were seen in the ED and were admitted or observed in the ED Chest Pain Unit (n = 215). Interviews were conducted within 48 hours with a structured set of questions. Results Thirty-one percent of white patients and 8.9% of African American patients were admitted with a diagnosis of acute myocardial infarction (P = .001). African American patients were as likely as white patients to report “typical” objective symptoms but were more likely to attribute their symptoms to a gastrointestinal source rather than a cardiac source (P = .05). Of those patients with the final diagnosis of myocardial infarction (n = 45), 61% of African American patients attributed symptoms to a gastrointestinal source and 11% to a cardiac source, versus 26% and 33%, respectively, for white patients. The median prehospital delay for African American patients was 263 minutes (interquartile range, 120 to 756 minutes), similar to the 247 minutes for white patients (interquartile range, 101 to 825 minutes, P = .72), despite African American patients (80%) being more likely than white patients (66%) to perceive their symptoms as severe/life-threatening at onset (P = .05). Conclusion Racial differences in symptom perception exist. Although the proportion of objectively defined typical symptoms were similar, self-attribution was more often noncardiac in African American patients than in white patients. Self-attribution, in addition to objective clinical findings, is likely to influence caregiver diagnostic approaches and therefore therapeutic approaches, and merits further study. (Am Heart J 2002;144:51-9.)     

Prognostic value of a negative stress echocardiographic study in diabetic patients

Background Diabetic patients have increased cardiovascular morbidity and mortality. We compared the long-term prognostic value of a negative, nonischemic stress echocardiogram in patients with and without diabetes. Methods Two hundred thirty-six consecutive subjects who had stress echocardiography and who were negative for inducible ischemia were included in the study. Baseline cardiac risk factors and cardiac events (cardiac death, nonfatal myocardial infarction, and coronary revascularization) were identified. Results Follow-up was obtained in 233 subjects for a mean duration of 25 months. There were 144 nondiabetic and 89 diabetic patients. At baseline, the diabetic group had a significantly higher incidence of hypertension, hyperlipidemia, and history of coronary artery disease but had a lower incidence of smoking (P < .05). Diabetic patients had a significantly higher incidence of cardiac events (19% vs 9.7%, P = .03) and worse event-free survival (P = .03). There were more nonfatal myocardial infarctions in the diabetic group (6.7% vs 1.4%, P < .05) and a trend toward a higher proportion of hard events (myocardial infarction and cardiac death) in diabetic patients (12.4% vs 5.6%, P = .11). The hard event rate per year of follow-up was 2.7% in nondiabetic and 6.0% in diabetic patients. In diabetic patients, a history of coronary artery disease was the only predictor of cardiac events (R = 0.18, P < .05). Conclusion Compared with nondiabetic patients, diabetic patients with negative stress echocardiograms are at greater risk for cardiac events. This appears to be due to a higher prevalence of established coronary disease in diabetic patients. (Am Heart J 2002;143:163-8.)     

Left atrial thrombus predicts transient ischemic attack in patients with atrial fibrillation

Background Atrial fibrillation (AF) is widely accepted as a direct cause of cardioembolic stroke from left atrial (LA) thrombus formation. However, the relationship between LA thrombus and transient ischemic attack (TIA) in patients with AF is less well established. Methods Two hundred sixty-one adult patients (mean age 66 ± 11 years, 220 men and 41 women) with AF undergoing transesophageal echocardiography (TEE) were prospectively followed up for TIA (mean duration 30.3 ± 20.6 months). Results LA thrombus was present in 18% (n = 46) and LA spontaneous echocardiographic contrast in 50% (n = 131) of the group. Nineteen of 261 patients had TIA during follow-up. Multivariate logistic regression showed congestive heart failure (CHF) as the only predictor of TIA when a model of clinical variables was constructed (odds ratio [OR] 2.7, P = .04). Age, sex, hypertension, and use of warfarin or aspirin were not predictors. When TEE variables were added to the model, LA thrombus became the only predictor of TIA (OR 7.7, P = .0001). Survival free of TIA (Kaplan-Meier) was significantly less (P = .0001) in patients with LA thrombus compared with those without, and the annual TIA event rate was 9.2% per year versus 1.9% per year (P <.0001), respectively. Conclusions To our knowledge, this is the first prospective study documenting an association between LA thrombus and TIA in patients with AF. Other TEE variables, including aortic atheromata, and clinical parameters were not independently predictive. These data support a likely thromboembolic mechanism for TIA from LA thrombus in patients with AF.     

Beneficial effects of metoprolol on myocardial sympathetic function: Evidence from a randomized,placebo-controlled study in patients with congestive heart failure

Background We sought to investigate whether β-blockers exert a presynaptic effect in the myocardium as measured by ¹²³I-metaiodobenzylguanidine. Methods The study comprised 59 patients with congestive heart failure, New York Heart Association class II or III, and left ventricular ejection fraction <35%. After an open label titration phase, patients were randomized to their maximal tolerable dose of metoprolol or placebo. Myocardial MIBG uptake was measured before the titration phase and after 6 months of treatment. Other parameters were maximal oxygen consumption, 6-minute walking test, plasma neurohormones, and echocardiographic parameters. Results We found a 21.9% increase in mean myocardial MIBG uptake after 6 months of treatment with metoprolol. In contrast, MIBG uptake decreased by 7.8% in the placebo group (P = 0.03 compared with metoprolol). Left ventricular end-diastolic diameter decreased from 74 ± 11 mm to 67 ± 10 mm (P < .05, within-group comparison) and LVEF increased from 25.3% ± 7.4% to 32.6% ± 9.6% (P < .05, within-group comparison) in the metoprolol group. Placebo-treated patients showed no significant changes. Comparison of changes in left ventricular end-diastolic diameter and LVEF between metoprolol and placebo did not reach statistical significance (P = 0.2). Conclusions This randomized, placebo-controlled study demonstrates that metoprolol has a presynaptic effect as measured by myocardial MIBG scintigraphy in both ischemic and nonischemic cardiomyopathy. (Am Heart J 2002;144:e3.)     

Effects of exercise training in patients with heart failure: the Exercise Rehabilitation Trial (EXERT)

Background The purpose of this study was to examine the effects of exercise training on functional capacity in patients with heart failure. Methods One hundred eighty-one patients in New York Heart Association class I to III, with ejection fraction <40% and 6-minute walk distance <500 meters, were recruited into a randomized, controlled, single-blind trial comparing 3 months of supervised training, then 9 months of home-based training with usual care. Results There was a significant increase in 6-minute walk distance at 3 and 12 months but no between-group differences. Incremental peak oxygen uptake increased in the exercise group compared with the control group at 3 months (0.104 ± 0.026 L/min vs 0.025 ± 0.023 L/min; P = .026) and 12 months (0.154 ± 0.074 L/min vs 0.024 ± 0.027 L/min; P = .081). Compared with the control group, significant increases were observed in the exercise group for arm and leg strength. No significant changes were observed in cardiac function or quality of life. Adherence to exercise was good during supervised training but reduced during home-based training. Conclusions Exercise training improves peak oxygen uptake and strength during supervised training. Over the final 9 months of the study, there was little further improvement, suggesting that some supervision is required for these patients. There were no adverse effects on cardiac function or clinical events. (Am Heart J 2002;144:23-30.)     

Outcome of the pelvic pouch procedure in patients with prior perianal disease

PURPOSE: There is concern that patients with presumed ulcerative colitis and significant perianal disease may in fact have Crohn's disease. Moreover, prior perianal disease may be an independent factor for poor outcome of the pelvic pouch. The aim of this study was to evaluate the effect of prior perianal disease on pelvic pouch outcome. METHODS: Between 1982 and 1994, 52 of 753 patients (6.9 percent) who had a pelvic pouch procedure were prospectively identified as having perianal disease. Outcome of the pelvic pouch of these 52 patients (Group I) were compared with the outcome of 701 pelvic pouch patients with no prior perianal disease (Group II). The perianal diseases identified in Group I were fissure-in-ano (17), perianal abscesses (13), fistula-in-ano (7), rectovaginal fistula (3), and significant hemorrhoids/skin tags (25). Eleven patients (21 percent) had more than one type of perianal disease. Twenty-seven patients (52 percent) required a total of 33 perianal operations for the different anal pathologies. RESULTS: Both groups were comparable for the following characteristics: age at time of pelvic pouch procedure, pathology (ulcerative colitis or indeterminate colitis), design of pouch, and type of ileoanal anastomosis (handsewn or stapled). An ileoanal anastomosis leak developed in 21 percent of patients (n=11) in Group I vs.11.4 percent (n=80) in Group II (P<0.05). Perianal postoperative complications occurred in 11.5 percent of patients (n=6) in Group I vs.1.7 percent (n=12) in Group II (P<0.05). Total pouch failure rate was not significantly different between the two groups (11.5 vs.7.6 percent;P>0.05). Crohn's disease was subsequently diagnosed in 1.9 vs.2.7 percent (P>0.05). Subgroup analysis of Group I patients showed no significant difference in outcome according to type of perianal lesion or a history of perianal surgery. CONCLUSION: Prior perianal disease significantly increases the risk of developing an ileoanal anastomotic leak and postoperative perianal complications. However, a pelvic pouch procedure may be an acceptable surgical alternative for selected ulcerative colitis patients with prior perianal disease because the overall pouch failure rate is not significantly increased.     

Elective versus provisional intra-aortic balloon pumping in high-risk percutaneous transluminal coronary angioplasty

Background Elective intra-aortic balloon pump (IABP) support may reduce acute complications occurring during percutaneous coronary interventions (PCI) in patients with severe depression of the left ventricular ejection fraction (EF ≤ 30%). Methods Since February 1998, 133 consecutive patients with EF ≤30% underwent elective PCI in our institution; 61 had elective preprocedural IABP support (group A) and 72 patients had conventional PCI (group B). Jeopardy score was calculated in each patient from the coronary angiograms to quantify the myocardium at risk. Results EF was similar in the 2 groups. Jeopardy score was higher in group A (8.0 ± 2.8 vs 6.7 ± 2.4, P = .008). The other principal clinical and angiographic characteristics were similar in the 2 groups. Severe hypotension and/or shock occurred in 11 patients, all in group B (P = .001). All required urgent IABP support, and 3 eventually died. Intraprocedural major adverse cardiac and cerebral events (eg, myocardial infarction, severe hypotension and/or shock, urgent bypass surgery, stroke, and death) were higher in group B (17% vs 0%, P = .001). By stepwise logistic regression analysis, elective IABP support (odds ration [OR] 0.11 [95% CI 0.21-0.60], P = .011), jeopardy score (OR 5.37 [95% CI 1.10-8.70], P = .040), and female sex (OR 2.72 [95% CI 1.85-3.10], P = .015), were the correlates of intraprocedural events. Conclusions This study supports the potential usefulness of elective versus provisional IABP to prevent intraprocedural major adverse cardiac and cerebral events in high-risk PCI. (Am Heart J 2003;145:700-7.)