Keiichi Ito

Stromelysin promoter 5A/6A polymorphism is associated with acute myocardial infarction.

BACKGROUND Rupture of the fibrous cap of an atherosclerotic plaque is a key event that predisposes to acute myocardial infarction (AMI). Matrix metalloproteinases (MMPs) may contribute to weakening of the cap, which favors rupture. Stromelysin, a member of MMP family, is identified extensively in human coronary atherosclerotic lesions. It can degrade most of the constituents of extracellular matrix as well as activating other MMPs, which suggests that it may play an important role in plaque rupture. Recently, a common variant (5A/6A) in the promoter of the stromelysin gene has been identified. The 5A/6A polymorphism could regulate the transcription of the stromelysin gene in an allele-specific manner. METHODS AND RESULTS To investigate the relation between the 5A/6A polymorphism in the promoter of the stromelysin gene and AMI, we conducted a case-control study of 330 AMI patients and 330 control subjects. The prevalence of the 5A/6A+5A/5A genotype was significantly more frequent in the patients with AMI than in control subjects (48.8% vs 32.7%, P<0.0001). In logistic regression models, the odds ratio of the 5A/6A+5A/5A was 2.25 (95% CI, 1.51 to 3.35). The association of 5A/6A polymorphism with AMI was statistically significant and independent of other risk factors. CONCLUSIONS The 5A/6A polymorphism in the promoter of the stromelysin gene is a novel pathogenetic risk factor for AMI.

Repeated provocation of time- and ATP-induced early pulmonary vein reconnections after pulmonary vein isolation: eliminating paroxysmal atrial fibrillation in a single procedure.

Background— Recurrence of atrial fibrillation (AF) after successful pulmonary vein isolation (PVI) occurs mainly due to the reconnection of the once isolated PV. Although provocation and elimination of the early pulmonary vein reconnection (EPVR) soon after PVI has been widely performed to improve the outcome, AF recurrence due to subsequent PV reconnections still occurs. In this study, we repeatedly provoked and eliminated the EPVR to determine the appropriate procedural end point. Methods and Results— Seventy-five patients with paroxysmal AF underwent PVI. EPVR was provoked by both time and ATP induction every 30 minutes until 90 minutes after the individual isolation of all PVs. The number of reconnected atrio-PV gaps were evaluated and reablated at each provocation step. Although both time- and ATP-dependent EPVR was induced most frequently at 30 minutes after PVI (75 and 76 gaps, respectively), the prevalence of induced EPVR at 60 minutes was still high (64 and 36 gaps induced by time and ATP, respectively). Only a small number of EPVR appeared at 90 minutes after the elimination of all EPVR by 60 minutes (8 gaps, P<0.01). During the mean follow-up period of 370 days, 92% of cases were free from AF without antiarrhythmic drugs. Conclusions— Provocation and elimination of time- and ATP-induced EPVR not only at 30 minutes but also at 60 minutes is recommended after PVI to improve its efficacy.Background— Recurrence of atrial fibrillation (AF) after successful pulmonary vein isolation (PVI) occurs mainly due to the reconnection of the once isolated PV. Although provocation and elimination of the early pulmonary vein reconnection (EPVR) soon after PVI has been widely performed to improve the outcome, AF recurrence due to subsequent PV reconnections still occurs. In this study, we repeatedly provoked and eliminated the EPVR to determine the appropriate procedural end point. Methods and Results— Seventy-five patients with paroxysmal AF underwent PVI. EPVR was provoked by both time and ATP induction every 30 minutes until 90 minutes after the individual isolation of all PVs. The number of reconnected atrio-PV gaps were evaluated and reablated at each provocation step. Although both time- and ATP-dependent EPVR was induced most frequently at 30 minutes after PVI (75 and 76 gaps, respectively), the prevalence of induced EPVR at 60 minutes was still high (64 and 36 gaps induced by time and ATP, respectively). Only a small number of EPVR appeared at 90 minutes after the elimination of all EPVR by 60 minutes (8 gaps, P <0.01). During the mean follow-up period of 370 days, 92% of cases were free from AF without antiarrhythmic drugs. Conclusions— Provocation and elimination of time- and ATP-induced EPVR not only at 30 minutes but also at 60 minutes is recommended after PVI to improve its efficacy.

T102C polymorphism of the serotonin (5-HT) 2A receptor gene in patients with non-fatal acute myocardial infarction

Serotonin (5-HT), released from activated platelets, has been implicated in the pathogenesis of acute myocardial infarction (AMI). 5-HT induces platelet aggregation and vascular contraction through 5-HT2A receptor activation at sites of coronary atherosclerosis, leading to thrombus formation. Recently, a 5-HT2A receptor gene T102C polymorphism has been reported to be associated with clinical response to 5-HT2A receptor antagonist in patients with schizophrenia, suggesting this polymorphism of the gene affects the 5-HT2A receptor function. To investigate the relationship between the T102C polymorphism and AMI, we conducted a case-control study of 255 non-fatal AMI patients and 255 control subjects. Among the patients, the prevalence of TT genotype was significantly higher than in controls (32.5 vs. 24.3%; P<0.05). In male patients (n=216), the prevalence was much higher than in control subjects (33.8 vs. 24. 1%, P<0.03). In multiple logistic regression models, odds ratio of TT genotype was 1.45 (95% CI 0.96-2.20) in all and 1.61 (95% CI 1. 03-2.53) (P<0.05) in males. The association of T102C polymorphism of the 5-HT2A receptor gene with non-fatal AMI was statistically significant and independent of other risk factors in males. The TT genotype of the 5-HT2A receptor gene may enhance susceptibility to AMI. Our observations suggest that the T102C polymorphism of the 5-HT2A receptor gene can serve as a new genetic marker for AMI.

Comparison of effects of ascorbic acid on endothelium-dependent vasodilation in patients with chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy versus patients with effort angina pectoris secondary to coronary artery disease

Impaired endothelium-dependent vasodilation has been reported to play an important role in the pathogenesis of cardiovascular diseases such as coronary artery disease (CAD) and congestive heart failure (CHF). However, the precise mechanism of endothelial dysfunction has not been elucidated in these conditions. To evaluate the role of oxidative stress in endothelial dysfunction, the effect of antioxidant ascorbic acid on brachial flow-mediated, endothelium-dependent vasodilation during reactive hyperemia and nitroglycerin-induced endothelium-independent vasodilation was examined with high resolution ultrasound in 12 patients with CHF caused by idiopathic dilated cardiomyopathy without established coronary atherosclerosis and in 10 patients with CAD. Flow-mediated vasodilation in CHF (4.4+/-0.5%) and CAD (4.0 - 0.8%) was significantly (p <0.05) attenuated compared with that in 10 control subjects (9.6+/-0.9%). However, nitroglycerin-induced vasodilation was similar in 3 groups (13.7+/-1.3% in control, 13.9+/-1.1% in CHF, 12.7+/-1.4% in CAD). Ascorbic acid could significantly improve flow-mediated vasodilation only in patients with CAD (9.1+/-0.9%) but not with CHF (5.6+/-0.6%), and had no influence on nitroglycerin-induced vasodilation (13.6+/-1.1% in CHF, 14.0+/-1.3% in CAD). These results suggest that, in brachial circulation, augmented oxidative stress mainly leads to endothelial dysfunction in CAD but not in CHF caused by idiopathic dilated cardiomyopathy.

Systemic Endothelial Function Is Preserved in Men With Both Active and Inactive Variant Angina Pectoris

To test the hypothesis that coronary spasm could be a coronary manifestation of systemic endothelial dysfunction and that the activity of coronary spasm could influence systemic endothelial function, we examined brachial flow-mediated, endothelium-dependent vasodilation and nitroglycerin-induced endothelium-independent vasodilation with high-resolution ultrasound in 11 men with variant angina pectoris (6 active and 5 inactive) without established coronary atherosclerosis. Endothelium-dependent vasodilation in peripheral circulation was preserved in men with active and inactive variant angina pectoris, suggesting that systemic endothelial dysfunction is not involved in either the pathogenesis or the activity of coronary spasm.

Extra-cardiac Factors Could Alter Plasma B-type Natriuretic Peptide Levels Independent of Cardiac Function.

The assessment of plasma B-type natriuretic peptide (BNP) levels is used for early detection, diagnosis, assessment of the severity of congestive heart failure (CHF), as well as assessments of the effects of therapy and the prognosis of patients with CHF. However extra-cardiac factors could directly alter plasma BNP levels independent of cardiac function and might alter the relationship between them.We investigated the relationship between the BNP level or it’s amelioration and clinical factors, including factors, male gender, age, body mass index (BMI), renal function, degrees of inflammations (serum CRP levels) and echocardiographic parameters in patients with various cardiovascular diseases.From our investigation, plasma BNP levels were affected by extra-cardiac factors and older age, low BMI, renal dysfunction, high serum CRP level, and probably diastolic dysfunction rather than systolic dysfunction act against the amelioration of BNP. In particular, low levels of plasma BNP in patients with high BMI should be carefully considered in order to avoid underestimating the degree of heart failure which was assessed using chest X-rays and plasma BNP levels. In addition, plasma BNP levels increased with the severity of cardiac dysfunction and serum CRP levels, and should therefore be considered to be a collective or total marker for life-threatening conditions including systemic inflammation, and not simply as a marker of cardiac dysfunction in patients with cardiovascular diseases.

Repeated Provocation of Time- and ATP-Induced Early Pulmonary Vein Reconnections After Pulmonary Vein IsolationClinical Perspective: Eliminating Paroxysmal Atrial Fibrillation in a Single Procedure

Background— Recurrence of atrial fibrillation (AF) after successful pulmonary vein isolation (PVI) occurs mainly due to the reconnection of the once isolated PV. Although provocation and elimination of the early pulmonary vein reconnection (EPVR) soon after PVI has been widely performed to improve the outcome, AF recurrence due to subsequent PV reconnections still occurs. In this study, we repeatedly provoked and eliminated the EPVR to determine the appropriate procedural end point. Methods and Results— Seventy-five patients with paroxysmal AF underwent PVI. EPVR was provoked by both time and ATP induction every 30 minutes until 90 minutes after the individual isolation of all PVs. The number of reconnected atrio-PV gaps were evaluated and reablated at each provocation step. Although both time- and ATP-dependent EPVR was induced most frequently at 30 minutes after PVI (75 and 76 gaps, respectively), the prevalence of induced EPVR at 60 minutes was still high (64 and 36 gaps induced by time and ATP, respectively). Only a small number of EPVR appeared at 90 minutes after the elimination of all EPVR by 60 minutes (8 gaps, P<0.01). During the mean follow-up period of 370 days, 92% of cases were free from AF without antiarrhythmic drugs. Conclusions— Provocation and elimination of time- and ATP-induced EPVR not only at 30 minutes but also at 60 minutes is recommended after PVI to improve its efficacy.Background— Recurrence of atrial fibrillation (AF) after successful pulmonary vein isolation (PVI) occurs mainly due to the reconnection of the once isolated PV. Although provocation and elimination of the early pulmonary vein reconnection (EPVR) soon after PVI has been widely performed to improve the outcome, AF recurrence due to subsequent PV reconnections still occurs. In this study, we repeatedly provoked and eliminated the EPVR to determine the appropriate procedural end point. Methods and Results— Seventy-five patients with paroxysmal AF underwent PVI. EPVR was provoked by both time and ATP induction every 30 minutes until 90 minutes after the individual isolation of all PVs. The number of reconnected atrio-PV gaps were evaluated and reablated at each provocation step. Although both time- and ATP-dependent EPVR was induced most frequently at 30 minutes after PVI (75 and 76 gaps, respectively), the prevalence of induced EPVR at 60 minutes was still high (64 and 36 gaps induced by time and ATP, respectively). Only a small number of EPVR appeared at 90 minutes after the elimination of all EPVR by 60 minutes (8 gaps, P <0.01). During the mean follow-up period of 370 days, 92% of cases were free from AF without antiarrhythmic drugs. Conclusions— Provocation and elimination of time- and ATP-induced EPVR not only at 30 minutes but also at 60 minutes is recommended after PVI to improve its efficacy.

Repeated Provocation of Time- and ATP-Induced Early Pulmonary Vein Reconnections After Pulmonary Vein IsolationClinical Perspective

Background— Recurrence of atrial fibrillation (AF) after successful pulmonary vein isolation (PVI) occurs mainly due to the reconnection of the once isolated PV. Although provocation and elimination of the early pulmonary vein reconnection (EPVR) soon after PVI has been widely performed to improve the outcome, AF recurrence due to subsequent PV reconnections still occurs. In this study, we repeatedly provoked and eliminated the EPVR to determine the appropriate procedural end point. Methods and Results— Seventy-five patients with paroxysmal AF underwent PVI. EPVR was provoked by both time and ATP induction every 30 minutes until 90 minutes after the individual isolation of all PVs. The number of reconnected atrio-PV gaps were evaluated and reablated at each provocation step. Although both time- and ATP-dependent EPVR was induced most frequently at 30 minutes after PVI (75 and 76 gaps, respectively), the prevalence of induced EPVR at 60 minutes was still high (64 and 36 gaps induced by time and ATP, respectively). Only a small number of EPVR appeared at 90 minutes after the elimination of all EPVR by 60 minutes (8 gaps, P<0.01). During the mean follow-up period of 370 days, 92% of cases were free from AF without antiarrhythmic drugs. Conclusions— Provocation and elimination of time- and ATP-induced EPVR not only at 30 minutes but also at 60 minutes is recommended after PVI to improve its efficacy.Background— Recurrence of atrial fibrillation (AF) after successful pulmonary vein isolation (PVI) occurs mainly due to the reconnection of the once isolated PV. Although provocation and elimination of the early pulmonary vein reconnection (EPVR) soon after PVI has been widely performed to improve the outcome, AF recurrence due to subsequent PV reconnections still occurs. In this study, we repeatedly provoked and eliminated the EPVR to determine the appropriate procedural end point. Methods and Results— Seventy-five patients with paroxysmal AF underwent PVI. EPVR was provoked by both time and ATP induction every 30 minutes until 90 minutes after the individual isolation of all PVs. The number of reconnected atrio-PV gaps were evaluated and reablated at each provocation step. Although both time- and ATP-dependent EPVR was induced most frequently at 30 minutes after PVI (75 and 76 gaps, respectively), the prevalence of induced EPVR at 60 minutes was still high (64 and 36 gaps induced by time and ATP, respectively). Only a small number of EPVR appeared at 90 minutes after the elimination of all EPVR by 60 minutes (8 gaps, P <0.01). During the mean follow-up period of 370 days, 92% of cases were free from AF without antiarrhythmic drugs. Conclusions— Provocation and elimination of time- and ATP-induced EPVR not only at 30 minutes but also at 60 minutes is recommended after PVI to improve its efficacy.