Low-dose aspirin for prevention of stroke in low-risk patients with atrial fibrillation: Japan Atrial Fibrillation Stroke Trial.

BACKGROUND AND PURPOSE: Although the efficacy of anticoagulant therapy for primary prevention of stroke in patients with nonvalvular atrial fibrillation (NVAF) has been established, efficacy of antiplatelet therapy for low-risk patients is disputable in Japanese patients because of the frequent hemorrhagic complications. We examined the efficacy and safety of aspirin therapy in Japanese patients with NVAF in a prospective randomized multicenter trial. METHODS: Patients with NVAF were randomized to an aspirin group (aspirin at 150 to 200 mg per day) or a control group without antiplatelet or anticoagulant therapy. Primary end points included cardiovascular death, symptomatic brain infarction, or transient ischemic attack. RESULTS: A total of 426 patients were randomized to aspirin group and 445 to no treatment. The trial was stopped earlier because there were 27 primary end point events (3.1% per year; 95% CI, 2.1% to 4.6% per year) in the aspirin group versus 23 (2.4% per year; 95% CI, 1.5% to 3.5% per year) in the control group, suggesting a low possibility of superiority of the aspirin treatment for prevention of the primary end point. In addition, treatment with aspirin caused a marginally increased risk of major bleeding (7 patients; 1.6%) compared with the control group (2 patients; 0.4%; Fisher exact test P=0.101). CONCLUSIONS: For prevention of stroke in patients with NVAF, aspirin at 150 to 200 mg per day does not seem to be either effective or safe. Further prospective studies are needed to determine the best preventive therapy for cerebrovascular events in Japanese patients with NVAF.

Plaque erosion in the culprit lesion is prone to develop a smaller myocardial infarction size compared with plaque rupture.

BACKGROUND: Acute myocardial infarction (MI) stems from a disruption of the plaque in the coronary artery. Based on postmortem examinations, such plaque disruption has been classified as either a rupture or an erosion. Unfortunately, it has been difficult to clinically identify plaque ruptures and plaque erosions during the development of acute MI. To elucidate the relationships between clinical features and the morphological characteristics of the infarct-related lesions, we observed the culprit lesions in patients with acute MI by coronary angioscopy and intravascular ultrasound. METHODS: We examined culprit lesions in 107 patients with acute MI using coronary angioscopy and intravascular ultrasound immediately before performing percutaneous coronary intervention. The lesions were then classified as plaque ruptures or nonruptured erosions, and their clinical features were compared. RESULTS: Among the lesions studied, 44 were classified as plaque ruptures, 28 were classified as plaque erosions, and 35 were unclassified. Patients with nonruptured eroded plaques had more preinfarction angina before the onset of MI than those with ruptured plaques (53.6% vs 22.7%, P = .0074). They also had less ST-segment elevation MI (71.4% vs 93.2%, P = .0185), lower peak creatine kinase levels (2029 +/- 1517 vs 4033 +/- 2699 IU/L, P = .0009), less distal embolization after percutaneous coronary intervention (3.6% vs 36.4%, P = .0014), and less Q-wave MI 1 month after onset (40.7% vs 88.4%, P < .0001). CONCLUSION: Patients with eroded plaque lesions have smaller infarctions than those with ruptured plaque lesions, suggesting that an eroded plaque is less potently thrombogenic than a ruptured plaque.

Usefulness of ST-segment elevation in the inferior leads in predicting ventricular septal rupture in patients with anterior wall acute myocardial infarction.

The ventricular septum receives its blood supply from the septal perforators of the left anterior descending (LAD) coronary artery and the right coronary artery. However, when the LAD artery extends to the inferior wall, beyond the apex (so-called wrapped LAD), the ventricular septum near the apex receives blood supply only from the LAD artery. As a consequence, ventricular septal rupture (VSR) would seem more likely in myocardial infarction with occlusion of this type of LAD artery. To test this hypothesis, we compared electrocardiographic findings in 21 patients who had anterior acute myocardial infarction that was complicated by VSR with those in 275 patients who had acute myocardial infarction that was not complicated by VSR. We observed ST-segment elevation in all inferior leads (II, III, and aVF) in addition to anterior leads in 42.9% of patients (9 of 21) who had VSR but in only 3.6% of those (10 of 275) who did not have VSR. Abnormal Q waves appeared in all 3 inferior leads in 44.4% of patients (8 of 18) who had VSR but in only 4.0% of those (10 of 250) who did not have VSR. Thus, the incidence of ST-segment elevation and abnormal Q waves in the inferior leads was significantly (p <0.001) greater in the VSR group. In addition, multivariate analysis of patient characteristics, including advanced age, female gender, and coronary morphology, showed VSR to be significantly correlated with ST-segment elevation (odds ratio 16.93, 95% confidence interval 4.13 to 69.30) and abnormal Q waves (odds ratio 13.64, 95% confidence interval 3.16 to 58.79) in the 3 inferior leads. In conclusion, these electrocardiographic findings can be useful predictors of complication by VSR.

Comparison of risk factors in acute myocardial infarction and unstable angina pectoris in patients < or =66 versus >66 years of age.

A prospective study was conducted of the differences in clinical characteristics between patients with acute myocardial infarction and those with unstable angina pectoris admitted to hospitals in the South-Osaka district of Japan. Gender and smoking were identified as discriminant risk factors for the incidence of acute myocardial infarction in patients < or =66 years with acute coronary syndromes; however, age alone affected the mode of presentation in older patients.

Cardioprotection by metformin is abolished by a nitric oxide synthase inhibitor in ischemic rabbit hearts.

We investigated the effects of metformin on myocardial metabolism during ischemia by 31P-nuclear magnetic resonance (NMR) in isolated rabbit hearts. Metformin was administered 60 min prior to induction of global ischemia, or in combination with a nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), at 5 min or 60 min prior to the ischemia. Normothermic global ischemia was then carried out for 45 min. Twenty-eight hearts were divided into 4 experimental groups consisting of 7 hearts each: a control (C) group; an M group receiving metformin treatment alone; an M+L (5) group receiving metformin treatment with L-NAME at 5 min before ischemia; and an M+L (60) group receiving metformin treatment with L-NAME at 60 min before ischemia. During ischemia, the decrease in adenosine triphosphate (ATP) was significantly inhibited in the M group in comparison with the C group (p < 0.01). However, this preservation of ATP in the M group was inhibited in the M+L (5) group during ischemia. In contrast, in the M+L (60) group, this preservation of ATP in the M group was not inhibited during, but not at the end of, ischemia. These results suggest that metformin has a significant beneficial effect for improving the myocardial energy metabolism during myocardial ischemia. This cardioprotection may be more dependent on nitric oxide synthase during ischemia than during pre-ischemia.

Effects of an HMG-CoA reductase inhibitor in combination with an ACE inhibitor or angiotensin II type 1 receptor antagonist on myocardial metabolism in ischemic rabbit hearts.

We investigated the effects of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, pravastatin, an angiotensin converting enzyme (ACE) inhibitor, temocaprilat, and an angiotensin II type 1 (AT1) receptor antagonist, CV-11974, on myocardial metabolism during ischemia in isolated rabbit hearts using phosphorus 31-nuclear magnetic resonance (31P-NMR) imaging. Forty-five minutes of continuous normothermic global ischemia was carried out. Pravastatin, temocaprilat, CV-11974 or a nitric oxide synthase inhibitor, L-NAME was administered from 60 min prior to the global ischemia. Japanese white rabbits were divided into the following experimental groups, a control group (n=7), a group treated with pravastatin (P group; n=7), a group treated with pravastatin and temocaprilat (P+T group; n=7), a group treated with pravastatin and CV-11974 (P+CV group; n=7), and a group treated with pravastatin and L-NAME (P+L-NAME group; n=7). During ischemia, P group, as well as either P+T group or P+CV group, showed a significant inhibition of the decreases in adenosine triphosphate (ATP) and intracellular pH (pHi) (p<0.01, respectively, at the end of ischemia compared to the control group as well as P+L-NAME group), and a significant inhibition of the increase in inorganic phosphate (Pi) (p<0.01, respectively, compared with the control group as well as P+L-NAME group). These results suggest that pravastatin significantly improved myocardial energy metabolism during myocardial ischemia. This beneficial effect was dependent on NO synthase. However, this beneficial effect was not enhanced by either temocaprilat or CV-11974.

A novel cardioprotective agent, JTV-519, is abolished by nitric oxide synthase inhibitor on myocardial metabolism in ischemia-reperfused rabbit hearts.

We investigated the effect of a novel cardioprotective agent, JTV-519, with or without a nitric oxide synthase inhibitor, L-NAME, on the myocardial metabolism and contraction during ischemia and reperfusion by means of phosphorus 31-nuclear magnetic resonance (31P-NMR) in Langendorff rabbit hearts. After 20 min normothermic global ischemia, postischemic reperfusion was carried out for 30 min. JTV-519 was administered from 40 min prior to the global ischemia. Twenty-one hearts were divided into three experimental groups consisting of 7 hearts each: a control group, a JTV-519 group perfused with JTV-519, and a JTV-519+L-NAME group perfused with a combination of JTV-519 and L-NAME. During ischemia, the JTV-519 group showed a significant inhibition of the decrease in adenosine triphosphate (ATP) compared with both the control and JTV-519+L-NAME groups (p<0.01); the levels of ATP were 20+/-6, 56+/-9, and 40+/-4% in the control group, JTV-519 group, and JTV-519+L-NAME group, respectively. Both the JTV-519 group and JTV-519+L-NAME group showed a significant inhibition of the increase in left ventricular end-diastolic pressure (LVEDP) compared with the control group (p<0.01). After postischemic reperfusion, the JTV-519 group again showed a significant improvement of ATP as compared with both the control and JTV-519+L-NAME groups (p<0.01); the ATP levels were 52+/-4, 82+/-3, and 64+/-3% in the control group, JTV-519 group, and JTV-519+L-NAME group. In conclusion, JTV-519 has a significant beneficial effect on myocardial energy metabolism during both ischemia and reperfusion. This beneficial effect was dependent on NO synthase. Furthermore, JTV-519 showed significant potential for improving myocardial relaxation during ischemia. This effect was not dependent on NO synthase.

Eccentric dosing of nitrates does not increase cardiac events in patients with healed myocardial infarction.

This study was performed to investigate the risk of cardiac events by eccentric or continuous dosing of nitrates in patients with healed myocardial infarction. A total of 573 patients with healed myocardial infarction were assigned to one of two groups: a nitrate-treatment (n =239) and a nontreatment (n =334) group. The nitrate-treatment group was further subdivided into a group receiving eccentric dosing of nitrates (n =153) and a group receiving continuous dosing of nitrates (n =86). The mean observation period was 11.2+/-8.2 months. The cardiac events investigated were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure, sudden death, worsening angina and rebound angina. Baseline characteristics were also compared among the three groups to determine any effects on outcome. Among the patients receiving eccentric or continuous dosing of nitrates, the rates of cardiac events were 12.7/1,000 person.year and 67.4/1,000 person.year, respectively, whereas the rate was 19.7/1,000 person.year in the nontreated patients. The incidence of cardiac events was significantly greater in patients receiving continuous dosing of nitrates than in the nontreated patients (p <0.05). Continuous dosing of nitrates thus increases cardiac events, and while eccentric dosing of nitrates does not increase them, it is also not effective at preventing them in patients with healed myocardial infarction.

Diagnosis of vasospastic angina by hyperventilation and cold-pressor stress echocardiography: comparison to I-MIBG myocardial scintigraphy.

OBJECTIVES: We assessed the usefulness of hyperventilation and cold-pressor stress echocardiography in the diagnosis of vasospastic angina compared with that of iodine-123 metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy. BACKGROUND: Various noninvasive methods have been used to detect vasospastic angina, but they are not very sensitive in the diagnosis of vasospastic angina. 123I-MIBG images and stress echocardiography have recently been proposed as a useful tool for detecting vasospastic angina. METHOD: Thirty patients (21 males and 9 females, mean age: 52 +/- 14 years) who complained of rest angina were enrolled for this study. The hyperventilation and cold-pressor stress echocardiography test consisted of hyperventilation for 6 minutes, followed by cold water pressor for 2 minutes under continuous electrocardiographic and echocardiographic monitoring. Left ventricular regional wall motion by echocardiogram was analyzed by using the 16-segment model, and wall motion ranging from normokinesis to dyskinesis was evaluated visually in each segment. Single-photon emission computed tomography images of 123I-MIBG myocardial scintigraphy were divided into 26 segments. Defect scores were established using the 4 grades. The echocardiographic criteria for coronary spasm was worsening wall motion and the scintigraphic criteria was defect score more than moderately reduced. Acetylcholine was selectively injected into the right coronary artery (20 microg and 50 microg) and left coronary artery (20 microg, 50 microg, and 100 microg). RESULTS: Of 30 patients, 20 patients had coronary spasm on coronary angiography with an intracoronary injection of acetylcholine, whereas 10 patients showed no spasm. Multivessel spasms were observed in 15 patients. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of hyperventilation and cold-pressor stress echocardiography for diagnosing in patients with vasospastic angina were 90%, 90%, 95%, 82%, and 90%, respectively. However, those of 123I-MIBG myocardial scintigraphy for diagnosing in patients with vasospastic angina were 90%, 40%, 75%, 67%, and 73%, respectively. The specificity of hyperventilation and cold-pressor stress echocardiography was significantly higher than that of 123I-MIBG myocardial scintigraphy (P <.05). CONCLUSION: The specificity of hyperventilation and cold-pressor stress echocardiography in diagnosing coronary spasm were higher than that shown by 201I-MIBG myocardial scintigraphy.

Acromegaly with multiple cardiovascular complications--cardiomyopathy, chordae rupture of mitral valve, myocardial infarction and sick sinus syndrome.

A 62-year-old woman had acromegaly and developed congestive heart failure with cardiomyopathy, mitral regurgitation due to chordae rupture, coronary artery disease and sick sinus syndrome. Since congestive heart failure was resistant to medical therapy, mitral valve replacement, aortocoronary bypass surgery and implantation of permanent pacemaker were performed one month after her admission. Although acromegalic patients with cardiomyopathy are usually resistant to therapy, we successfully treated the patient by the surgeries. It appears that all these diseases resulted from an elevated plasma concentration of growth hormone. Untreated acromegaly for more than ten years may contribute to multiple complications such as those in the present patient.

Increased cardiac mortality in women compared with men in patients with acute myocardial infarction.

OBJECTIVE: It has been reported that women with acute myocardial infarction (AMI) have a higher short-term mortality rate than men, but the reason is not known. The profile in relation to age, gender and risk factors was evaluated to compare AMI and unstable angina pectoris (UAP). METHODS: Findings from 984 patients including 580 patients with AMI (129 women, 451 men) and 404 patients with UAP (131 women, 273 men) were analyzed by the South Osaka Acute Coronary Syndrome Study Group (SACS). The primary endpoint of the study was in-hospital death. The primary endpoints of interest (cardiac death) were fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death. RESULTS: Cardiac death during hospitalization within 30 days in AMI was higher in women than in men (12.4% vs 6.7%, p < 0.05). On the other hand, in UAP there was no significant difference between women and men (1.5% vs 0.7%, NS). The incidence of cardiac death in AMI was significantly higher for patients 75 years old and older (19.0%) than for patients less than 55 years old (4.2%), 55-64 years old (3.5%) and 65-74 years old (4.7%) (p < 0.001, respectively). CONCLUSIONS: Cardiac death was higher for women compared with men in patients with AMI. The worse prognosis for the AMI women patients was likely to be derived from less performance of percutaneous coronary intervention, and a high incidence of severe myocardial infarction. Further research should be focused on the analysis of various clinical backgrounds.

Haziness on coronary angiogram after percutaneous transluminal coronary angioplasty evaluated with angioscopy.

Coronary angiograms obtained after percutaneous transluminal coronary angioplasty are often hazy due to uneven distribution of contrast medium at the angioplasty site, In this study, structural changes resulting in haziness after percutaneous transluminal coronary angioplasty were identified angioscopically. The affected coronary arteries of 35 patients who underwent successful percutaneous transluminal coronary angioplasty were examined with angioscopy. Coronary angioscopic examination of the sites subjected to percutaneous transluminal coronary angioplasty revealed large surface disruptions in 17 cases, small surface disruptions in four cases, and thrombi in 24 cases. Angiographic haziness was recognized in 24 of 35 patients after percutaneous transluminal coronary angioplasty. Haziness on angiography was more significant in patients who exhibited large surface disruption (88% vs 50%, p < 0.05), and was significantly greater in patients who exhibited white thrombus (100% vs 56%, p<0.05). Moreover, it appears that percutaneous transluminal coronary angioplasty-induced large surface disruption and white thrombus likely play an important role in increasing haziness.

Long-term, continuous treatment with both oral and transdermal nitrates increases cardiac events in healed myocardial infarction patients.

This study was performed to investigate the effects of continuous dosing of oral, transdermal (patch), and a combination of the two with nitrate treatments on cardiac events in patients with healed myocardial infarction. In total, 1,291 patients with healed myocardial infarction were assigned 2 groups: treatment with nitrates (n=713) or nontreatment (n=578). Nitrate treatment was subdivided into 3 groups: patch group (n=149), oral group (n=504), and combination group (n=60). The mean observation period was 17.4 +/- 21.1 months. Primary end points were nonfatal and fatal recurrent myocardial infarction, death from congestive heart failure, and sudden death. Baseline characteristics were also compared among the 4 groups to determine any effects on outcome. Among the patients with patch, oral, and combination groups, cardiac events occurred 3.4%, 6.7%, 10.0%, respectively, whereas only 2.9% of the patients treated without nitrates had cardiac events. The incidence of cardiac events was significantly greater in patients with oral nitrates and combination groups compared to patients without nitrates (p<0.01, respectively). Continuous dosing of long-term treatment with both oral and transdermal nitrates increased cardiac events in healed myocardial infarction patients.

Efficacy of coronary angioplasty following conventional coronary thrombolysis in patients with acute myocardial infarction.

The efficacy of combined thrombolysis and angioplasty for the purpose of coronary reperfusion after acute myocardial infarction has been controversial. The present study was conducted, therefore, to evaluate the effects of angioplasty following administration of conventional thrombolytic agents on the long-term prognosis of acute myocardial infarction patients. A total of 409 patients admitted to the hospital within 12 hours of the onset of infarction between January 1990 and May 2001 were studied retrospectively. These included 151 patients treated with thrombolysis alone (group T), 73 patients treated with angioplasty alone (group A), and 35 patients treated with angioplasty after thrombolysis (group T&A). Group T&A had shorter intervals from onset to initial treatment than group A (3.0 hours vs 6.3 hours, p < 0.01), a higher reperfusion success rate than group T (91.4% vs 74.8%, p < 0.01), and more improved left ventricular wall motion than group A. One-year cardiac mortality rates tended to be higher in group T, which had a higher rate of unsuccessful reperfusion than groups T&A or A (8.1% vs 3.4% vs 3.5%). The frequencies of hemorrhagic complications were similar among the 3 groups. From these findings, we conclude that thrombolytic therapy with subsequent angioplasty is an effective strategy for achieving cardiac reperfusion following acute myocardial infarction.

Diagnosis of ischemic heart disease with exercise echocardiography: Comparison of images obtained at peak- and post-exercise.

Peak-and post-exercise stress echocardiography were compared with respect to ability to detect coronary artery disease in 138 consecutive patients undergoing supine bicycle stress echocardiography. Sixty of these patients had single-vessel disease; 37, double-vessel disease; and 19, triple-vessel disease. Exercise was performed in the 20- to 30-degree left decubitus position on an echo-bed with an ergometer. Exercise started at 50 watts and was increased in 25-watt every 3 minutes and to a maximum of 150 watts. Two-dimensional echocardiographic images were digitized and assigned in a quad-screen format for nonbiased interpretation. Total wall motion score (TWMS) was the sum of the wall motion score, from normokinesis (0) to dyskinesis (4), of 16 segments. Image quality score index (IQSI) was the mean of the image quality scores in all views. All of the patients underwent coronary arteriography. Significant coronary stenosis was defined as≧75% stenosis of the large coronary arteries. Two-dimensional echocardiographic studies were adequate for analysis in 133 patients during the peak-exercise stage (peak-exercise) and in 137 patients 30 to 60 seconds after the end of exercise (post-exercise). TWMS at peak-exercise was higher than at post-exercise, while IQSI at peak-exercise was lower than at post-exercise. Sensitivity at peak-exercise versus that at post-exercise was 91% versus 79% (p<0.05); specificity, 76% versus 85%; and diagnostic accuracy, 88% versus 80% (p<0.05), respectively. We conclude that despite poor image quality on exercise echocardiography, better diagnostic accuracy was attained by assessing wall motion changes at peak-exercise than at post-exercise.