Koichi Sakabe

Relation of Age and Sex to Atrial Electrophysiological Properties in Patients with No History of Atrial Fibrillation

Although atrial fibrillation is a common arrhythmia, especially in elderly men, little is known about age related changes in atrial electrophysiological properties or gender differences. The aim of this study was to analyze the effects of aging on vulnerability to atrial fibrillation and assessed gender differences in those age related changes. An electrophysiological study was performed on 73 patients with no history of atrial fibrillation, structural heart disease, or conditions with potential effects on cardiac hemodynamic or electrophysiological function, including 25 women (mean age 49 ± 18 years; range 12–84 years). The following atrial excitability parameters were assessed: spontaneous or paced (A1) and extrastimulated (A2) atrial electrogram widths, percent maximum atrial fragmentation (A2/A1 × 100) , effective refractory period, wavelength index (effective refractory period/A2), and inducibility of atrial fibrillation. There were no significant differences in percent maximum atrial fragmentation ( 143 ± 28 vs 142 ± 35% ), effective refractory period ( 241 ± 39 vs 238 ± 50 ms ), wavelength index ( 2.9 ± 0.8 vs 3.1 ± 0.9 ), induction of atrial fibrillation (10 [21%] vs 7 [28%]), or age ( 50 ± 17 vs 49 ± 20 years) between men and women. Age was not statistically different between those patients with and without induction of atrial fibrillation in men ( 48 ± 14 vs 50 ± 18 years ) and women ( 48 ± 18 vs 49 ± 21 years ). Percent maximum atrial fragmentation and effective refractory period were directly correlated with age in men ( r = 0.35, P = 0.01; r = 0.46, P < 0.001 , respectively) and women ( r = 0.42, P = 0.04; r = 0.45, P = 0.02 , respectively), though wavelength index did not correlate with age in men (r =−0.04) or women (r =−0.04) with no history of atrial fibrillation. Considering these findings, the authors conclude that the mechanism triggering atrial fibrillation may be different between older and younger patients with atrial fibrillation, because younger patients who have no marked substrate for atrial fibrillation may need many trigger beats to induce atrial fibrillation. (PACE 2003; 26:1238–1244)

Increased soluble platelet/endothelial cell adhesion molecule-1 in the early stages of acute coronary syndromes.

Specific molecules including inflammatory cell adhesion molecules mediate attachment of blood leukocyte and platelets to the endothelium and mononuclear cell migration into the arterial intima. However, the clinical significance of soluble cell adhesion molecules very early in the course of acute coronary syndrome is not known. We assayed platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31), intercellular adhesion molecule-1 (ICAM-1, CD54), and P-selectin (CD62P) in plasma obtained from 20 patients within 3 h after the onset of acute myocardial infarction (AMI); 16 patients with unstable angina pectoris; 20 patients with stable angina pectoris, and 28 controls. Blood samples were obtained on hospital admission and again 1 week after onset of AMI and unstable angina, and on admission in patients with stable angina and controls. Plasma PECAM-1 concentration (ng/ml) on admission was higher in patients with AMI (25.6+/-4.7) and unstable angina (24.7+/-4.4) than in stable angina (20.5+/-4.4) and control (18.8+/-3.8) groups. In both AMI and unstable angina, plasma PECAM-1 had decreased significantly by 1 week (AMI, 20.8+/-4.0; unstable angina, 21.0+/-4.1). Plasma ICAM-1 concentration (ng/ml) on admission was higher in patients with AMI (254+/-70), unstable angina (264+/-78), and stable angina (245+/-68) than in controls (201+/-56), but did not differ between the three coronary syndromes. Plasma P-selectin concentration did not differ between the four groups, including controls. Therefore, soluble PECAM-1 concentration may be a sensitive markers providing early diagnostic aid in acute coronary syndromes.

Interatrial dyssynchrony on tissue Doppler imaging predicts progression to chronic atrial fibrillation in patients with non-valvular paroxysmal atrial fibrillation

Objective: To determine prospectively whether interatrial dyssynchrony detected by tissue Doppler imaging (TDI) is useful for predicting the progression to chronic atrial fibrillation (CAF) in patients with non-valvular paroxysmal AF (PAF). Methods: Thirty-seven patients with non-valvular PAF were prospectively followed after echocardiography. The interval of time from initiation of the P wave on the electrocardiogram (ECG) until the beginning of the late diastolic TDI signal at the lateral border of the mitral annulus (P-A′(M)) and the tricuspid annulus (P-A′(T)) was measured. Interatrial dyssynchrony was defined as the difference between the P-A′(M) and P-A′(T) intervals (A′(M)-A′(T)). The study endpoint was the onset of CAF (>6 months). Results: During a follow-up period of 28 (SD 23) months, eight patients developed CAF. Compared with those without CAF, the patients who developed CAF had a significantly lower atrial systolic mitral (A′(M)) (7.7 (1.7) vs 10.7 (2.9) cm/s, p<0.01) and tricuspid (A′(T)) (12.9 (3.5) vs 16.6 (5.1) cm/s, p<0.05) annular tissue Doppler velocity, as well as a longer A′(M)-A′(T) interval (47 (13) vs 24 (10) ms, p<0.0001). Kaplan–Meier analysis, using cut-off values determined by analysis of receiver-operating characteristics curves, revealed that progression to CAF was significantly more frequent when the A′(M)-A′(T) interval was ⩾34 ms (p<0.01), the A′(M) velocity was ⩽9 cm/s (p<0.05) and the A′(T) velocity was ⩽16 cm/s (p<0.05). Conclusions: This prospective study suggests that non-valvular PAF patients with a high risk of developing CAF have “interatrial dyssynchrony” and “atrial systolic dysfunction” on atrial TDI.

Plasma concentrations of fibrinolytic factors in the subacute phase of myocardial infarction predict recurrent myocardial infarction or sudden cardiac death

BACKGROUND The prognostic value of plasma concentrations of tissue type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein has been reported in patients with coronary artery disease. However, the association between cardiac events and these factors during the acute and subacute phases of myocardial infarction (MI) is unknown. The purpose of this study was to determine whether elevated plasma concentrations of t-PA, PAI-1, and C-reactive protein in patients with MI are associated with future recurrent MI or sudden cardiac death. METHODS We studied 106 consecutive patients who survived a confirmed first MI between 1993 and 1998 in our hospital. The control group consisted of 50 patients who had no significant coronary artery stenosis. Blood samples were obtained at the time of admission for acute MI and on the 28th day after admission. Patients were followed for a mean of 50 months after these measurements. The primary end points were sudden cardiac death and fatal or nonfatal acute MI. RESULTS Of the 92 patients who were available for follow-up, 10 had cardiac events. Both the plasma t-PA and PAI-1 concentrations were elevated on day 1 of acute MI compared to the control group and decreased by day 28, but remained higher than those in the controls. Plasma C-reactive protein concentration was also elevated on day 1 and decreased by day 28. Using a stepwise variable choice model of Cox proportional hazards analysis including these fibrinolytic factors and C-reactive protein, only the t-PA concentration in the subacute phase was a significant predictor of cardiac events (relative risk per S.D. 3.20, P<0.01). We further found that independent of other risk factors, an elevated t-PA concentration was predictive of cardiac events. CONCLUSIONS This study reveals that a rise in endogenous t-PA concentration during the subacute phase of MI could predict recurrent MI or sudden cardiac death.

Transthoracic Doppler Echocardiographic Measurement of Left Atrial Appendage Blood Flow Velocity: Comparison with Transoesophageal Measurement

AIM We validated transthoracic echocardiographic measurements of left atrial appendage flow velocity by comparing them with transoesophageal echocardiographic measurements. METHODS AND RESULTS Eighty-four consecutive patients (mean age, 64.6 years) with various cardiac diseases, who underwent both transthoracic echocardiography and transoesophageal echocardiography were studied. Thirty-two patients were in sinus rhythm, and the remaining 52 patients were in atrial fibrillation. On transthoracic echocardiography, the transducer was placed somewhat superior and outside from the position viewing the conventional parasternal short-axis image of the aortic valve, so that the angle between left atrial appendage midline and Doppler beam could be narrowed. The left atrial appendage flow velocity pattern was recorded by pulsed Doppler mode with a sampling volume placed at the left atrial appendage orifice on both transthoracic echocardiography and transoesophageal echocardiography. In both approaches, the peak emptying velocity (LAA-E) and the peak filling velocity (LAA-F) of the left atrial appendage were measured. In sinus rhythm, the LAA-E was detectable in 25 of the 32 patients (78.1%) and the LAA-F in 20 of the 32 patients (62.5%). Both LAA-E and LAA-F were detectable in 46 of the 52 patients (88.5%) in atrial fibrillation. Good correlations of LAA-E and LAA-F were observed between transthoracic echocardiography and transoesophageal echocardiography measurements in sinus rhythm (r=0.94, r=0.95, respectively; both, P<0.0001) and in atrial fibrillation (r=0.89, r=0.95, respectively; both, P<0.0001). CONCLUSIONS The left atrial appendage flow velocities could be sufficiently recorded and assessed by transthoracic echocardiography in 84 Japanese unselected consecutive patients with sinus rhythm or atrial fibrillation.

Effects of angiotensin II receptor antagonists on [(123)I]metaiodobenzylguanidine myocardial imaging findings and neurohumoral factors in chronic heart failure.

Abstract Previous studies have not investigated the ef-ficacy of angiotensin II (AII) receptor antagonists against cardiac sympathetic overactivity in patients with chronic heart failure (CHF) using [123I]metaiodobenzylguanidine (MIBG) myocardial imaging. We studied 34 CHF patients with fractional shortening of the left ventricular (LV) diameter ≦25% or LV ejection fraction ≦45% in echocardiograms. An AII receptor antagonist (losartan or candesartan) was administered. Before and 6 months after the administration, MIBG myocardial imaging and echocardiography were performed, and neurohumoral factors were investigated. MIBG imaging revealed that the antagonist did not significantly change the heart-to-mediastinum ratio. However, the washout rate fell significantly (from 32.6% ± 7.6% to 28.2% ± 7.5%; P < 0.001). No significant changes occurred in LV diameter, fractional shortening, or LV ejection fraction. Circulating atrial (ANP) and brain natriuretic peptides (BNP), and aldosterone fell significantly. Changes in the MIBG washout rate correlated positively with changes in BNP (r = 0.35, P < 0.05). In 19 patients also being treated with angiotensin-converting enzyme (ACE) inhibitors, the MIBG washout rate also fell significantly with AII antagonists, as did BNP and aldosterone. The decreased MIBG washout and BNP in patients with CHF induced by the AII receptor antagonists suggests the efficacy of these agents in modifying cardiac sympathetic function and neurohumoral factors, even with ACE inhibition. Combination therapy with AII receptor antagonists and ACE inhibitors appears effective for CHF.

Relation of gender and interatrial dyssynchrony on tissue Doppler imaging to the prediction of the progression to chronic atrial fibrillation in patients with nonvalvular paroxysmal atrial fibrillation

This prospective study aimed to identify the relation of gender and interatrial dyssynchrony on tissue Doppler imaging (TDI) to the prediction of the progression to chronic atrial fibrillation (CAF) in nonvalvular paroxysmal AF (PAF) patients. Nineteen consecutive men and 19 women with nonvalvular PAF were prospectively followed after echocardiography. We measured the interval of time from initiation of the P wave on the electrocardiogram until the beginning of the late diastolic TDI signal at the lateral border of the mitral (P-A′(M)) and the tricuspid annulus (P-A′(T)). Interatrial dyssynchrony was defined as the difference between the P-A′(M) and P-A′(T) intervals (A′(M)-A′(T)). The study endpoint was the onset of CAF (>6 months). Six men developed CAF during a follow-up of 32 ± 26 months, and 3 women developed CAF during a follow-up of 25 ± 19 months. Compared to those without CAF, the patients with CAF had significantly longer A′(M)- A′(T) intervals (men: 41 ± 10 vs 27 ± 12 ms, women: 64 ± 4 vs 23 ± 9 ms; P < 0.01) in both genders. Kaplan-Meier analysis, using cutoff values determined by analysis of receiveroperating characteristics curves, revealed that the progression to CAF was significantly observed more often when A′(M)-A′(T) interval was >34 ms in men and >43 ms in women. This prospective study suggests that nonvalvular PAF men and women with a high risk of developing CAF have “interatrial dyssynchrony” on atrial TDI, whose cutoff values are shorter and may affect the vulnerability of AF in men.

Relation between circulating soluble Fas ligand and subsequent ventricular remodelling following myocardial infarction

The Fas/Fas ligand (Fas-L) system has been established as one of the regulatory pathways of apoptotic cell death. Fas is a type I membrane protein which belongs to the tumour necrosis factor/nerve growth factor receptor family and mediates apoptosis.1 A soluble form of Fas (sFas) found in sera of human subjects is thought to block apoptosis by inhibition of binding between Fas and the antibody to Fas on the cell membrane. Fas-L is a type II membrane protein in the tumour necrosis factor family, and human soluble Fas-L (sFas-L) apparently induces apoptosis of Fas expressing cells.1 Recently, the occurrence of apoptotic death of cardiomyocytes has been demonstrated experimentally after injury caused by hypoxia, reperfusion, myocardial infarction, and coronary embolism. However, only two clinical reports assessing the concentrations of circulating sFas and sFas-L in patients with acute myocardial infarction (AMI) have been published.2,3 No study has evaluated the relation between these concentrations and left ventricular (LV) remodelling following AMI. Thus, in this study we measured the circulating concentrations of sFas and sFas-L in patients with AMI. We also investigated the relation of sFas and sFas-L to LV remodelling after AMI. Fifty two consecutive patients (41 men; mean age 64 years) who presented with their first episode of AMI within 24 hours of symptom onset and who underwent successful coronary angioplasty were studied. Patients with significant concomitant diseases, such as malignancy, pulmonary disease, autoimmune disease, thyroid disease, or concurrent viral infection were excluded from this study. The control …

Coronary flow velocity patterns immediately after reperfusion reflect the pathologic characteristics of reperfused myocardium in canine models of acute myocardial infarction

BackgroundIt is difficult to evaluate the extent of myocardial injury after successful reperfusion following acute myocardial infarction (AMI). We investigated the relationship between the coronary flow velocity pattern immediately after reperfusion and pathologic characteristics after myocardial reperfusion injury in dogs. MethodsWe measured distal coronary flow velocity variables in the left circumflex coronary artery in a canine model of AMI (n = 12) 10 min after the release of a clamp (3–10 h clamp procedure) using a 0.35 mm Doppler guide-wire. Dogs were divided into two groups according to presence or absence of early systolic retrograde coronary flow. Hearts were excised 2 h after reperfusion and examined histopathologically. ResultsThe clamping time tended to be longer in dogs with early systolic retrograde coronary flow. Neutrophil infiltration was observed in the myocardium of dogs without systolic retrograde flow (n = 9); hemorrhage was rarely detectable and the myocardium maintained a bundle form. However, the bundle form of the myocardium became rough, and the severity of the incidence of hemorrhage tended to increase as the ratio of the diastolic coronary flow velocity to systolic velocity (DSVR) decreased. Vacuolar degeneration of the myocardium was also observed in hearts with a relatively low DSVR. In the group with systolic retrograde flow (n = 3), hearts were characterized by coagulation necrosis, marked vacuolar degeneration of the myocardium and diffusely distributed red cells in the intermyocytes. Systolic antegrade flow velocity was much reduced in this group, resulting in a markedly increased DSVR. These findings appeared to be related to severe myocardial damage. ConclusionsCoronary flow velocity patterns immediately after successful reperfusion appear to reflect the pathologic characteristics of the reperfused myocardium in dogs with AMI. Coronary Artery Dis 9:21–27

Coronary Flow Velocity Immediately After Reperfusion Reflects Myocardial Microcirculation in Canine Models of Acute Myocardial Infarction

Recent reports indicate that the coronary microcirculation is sometimes injured, despite successful reperfusion in acute myocardial infarction (AMI). However, it is difficult to evaluate the coronary microcirculation immediately after reperfusion by using only angiography. The purpose of this study was to examine the relationship between the pattern of coronary blood flow velocity and myocardial microcirculatory injury immedi ately after reperfusion in AMI. The authors recorded the left circumflex coronary flow velocity by using the Doppler guide wire method 10 minutes after reperfusion in a canine model of AMI. In addition, myocardial contrast echocardiography was performed with the injection of contrast medium into the left circumflex coronary artery before clamping of the coronary artery and 15 minutes after release of the clamp. From these images, the ratio of the normalized gray-level postreperfusion to preclamping in the contrast- enhanced area was determined. It was compared with coronary flow velocity variables. In the 10 dogs with a diastolic-to-systolic velocity ratio (DSVR) < 4.0, this velocity ratio 10 minutes after reperfusion correlated positively (r = 0.75, p < 0.01) with the normal ized gray-level ratio. However, the remaining three dogs with a DSVR ≥ 4.0 markedly deviated from this pattern. Coronary flow velocities in the three dogs were characterized by a greater decrease in systolic flow velocity and occurrence of early systolic retrograde flow. Myocardial contrast echocardiographic images in these three dogs demonstrated a lower normalized gray-level ratio. In conclusion, the coronary flow velocity pattern imme diately after reperfusion may reflect myocardial microcirculatory injury.