Masatake Fukunami

Detection of patients at risk for paroxysmal atrial fibrillation during sinus rhythm by P wave-triggered signal-averaged electrocardiogram.

To determine whether patients at risk for paroxysmal atrial fibrillation could be detected while in sinus rhythm, the signal-averaged electrocardiogram triggered by P waves was recorded in 42 patients with paroxysmal atrial fibrillation (Paf group) and in 50 control patients. The root mean square voltages (LP10, LP20, and LP30) for the last 10, 20, and 30 msec and the duration (Ad) of filtered (40—300 Hz) P wave of the spatial magnitude were measured. LP10 and LP20 were significantly lower in the Paf than in the control group (LP10, 1.92 ± 0.58 versus 2.49 ± 0.78, μV, p < 0.001; LP20, 2.47 ± 0.78 versus 3.46 ± 1.20, μV, p < 0.0001), although no significant difference in LP30 was found between groups. Ad was also significantly longer in the Paf than in the control group (137.0 ± 14.3 versus 118.6 ± 11.3 msec, p < 0.001). These differences between the Paf and control groups remained significant even after dividing by the presence or absence of organic heart diseases. The criteria of “LP20=3.5, μV or less” and “Ad > 120 msec” as defining “atrial late potential” gave a sensitivity of 91% and a specificity of 76%. These findings suggest that patients at risk for paroxysmal atrial fibrillation could be detected while in sinus rhythm by using the P wave-triggered signal-averaged electrocardiogram.

Cardiac Iodine-123 Metaiodobenzylguanidine Imaging Predicts Sudden Cardiac Death Independently of Left Ventricular Ejection Fraction in Patients With Chronic Heart Failure and Left Ventricular Systolic Dysfunction: Results From a Comparative Study With Signal-Averaged Electrocardiogram, Heart Rate Variability, and QT Dispersion

OBJECTIVES We prospectively compared the predictive value of cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging for sudden cardiac death (SCD) with that of the signal-averaged electrocardiogram (SAECG), heart rate variability (HRV), and QT dispersion in patients with chronic heart failure (CHF). BACKGROUND Cardiac MIBG imaging predicts prognosis of CHF patients. However, the long-term predictive value of MIBG imaging for SCD in this population remains to be elucidated. METHODS At entry, cardiac MIBG imaging, SAECG, 24-h Holter monitoring, and standard 12-lead electrocardiography (ECG) were performed in 106 consecutive stable CHF outpatients with a radionuclide left ventricular ejection fraction (LVEF) <40%. The cardiac MIBG washout rate (WR) was obtained from MIBG imaging. Furthermore, the time and frequency domain HRV parameters were calculated from 24-h Holter recordings, and QT dispersion was measured from the 12-lead ECG. RESULTS During a follow-up period of 65 +/- 31 months, 18 of 106 patients died suddenly. A multivariate Cox analysis revealed that WR and LVEF were significantly and independently associated with SCD, whereas the SAECG, HRV parameters, or QT dispersion were not. Patients with an abnormal WR (>27%) had a significantly higher risk of SCD (adjusted hazard ratio: 4.79, 95% confidence interval: 1.55 to 14.76). Even when confined to the patients with LVEF >35%, SCD was significantly more frequently observed in the patients with than without an abnormal WR (p = 0.02). CONCLUSIONS Cardiac MIBG WR, but not SAECG, HRV, or QT dispersion, is a powerful predictor of SCD in patients with mild-to-moderate CHF, independently of LVEF.

Increased intracardiovascular clotting in patients with chronic atrial fibrillation

To clarify whether the formation of thrombi could be induced by atrial fibrillation itself or by factors predisposing to atrial fibrillation such as mitral stenosis, plasma D-dimer levels (cross-linked fibrin degradation products) were measured in 73 patients without atrial fibrillation (Group 2). In Group 1, 49 of the 73 patients had factors predisposing to atrial fibrillation such as valvular heart disease, and the remaining 24 had lone atrial fibrillation. In Group 2, 16 patients had organic heart disease and the remaining 5 had a chest pain syndrome. The plasma D-dimer level was significantly higher in Group 1 (150 +/- 19 ng/ml) than in Group 2 (61 +/- 3 ng/ml) (p less than 0.01, mean +/- standard error of the mean). In both groups, there were no significant differences in plasma D-dimer level between patients with and without organic heart disease (146 +/- 18 versus 156 +/- 46 ng/ml in Group 1; 61 +/- 4 versus 59 +/- 10 ng/ml in Group 2). These findings indicate that atrial fibrillation itself may be more important than factors predisposing to atrial fibrillation in the development of intracardiovascular clotting.

Comparison of the prognostic value of cardiac iodine-123 metaiodobenzylguanidine imaging and heart rate variability in patients with chronic heart failure: a prospective study.

OBJECTIVES We sought to prospectively compare the prognostic value of cardiac iodine-123 (I-123) metaiodobenzylguanidine (MIBG) imaging with that of heart rate variability (HRV) in patients with mild-to-moderate chronic heart failure (HF). BACKGROUND Cardiac I-123 MIBG imaging, which reflects cardiac adrenergic nerve activity, provides prognostic information on chronic HF patients. Reduced HRV, indicating derangement in cardiac autonomic control, was also reported to be associated with a poor prognosis in chronic HF patients. METHODS At study entry, I-123 MIBG imaging and 24-h Holter monitoring were performed in 65 chronic HF outpatients with a radionuclide left ventricular ejection fraction <40%. The cardiac MIBG heart to mediastinum ratio (H/M) and washout rate (WR) were obtained from MIBG imaging. The time and frequency domain parameters of HRV were calculated from 24-h Holter recordings. RESULTS At a mean follow-up of 34 +/- 19 months, WR (p < 0.0001), H/M on the delayed image (p = 0.01), and normalized very-low-frequency power (n-VLFP) (p = 0.047) showed a significant association with the cardiac events (sudden death in 3 and hospitalization for worsening chronic HF in 10 patients) on univariate analysis. Multivariate analysis revealed that WR was the only independent predictor of cardiac events, although the predictive accuracy for the combination of abnormal WR and n-VLFP significantly increased, compared with that for abnormal WR (82% vs. 66%, p < 0.05). CONCLUSIONS Cardiac MIBG WR has a higher prognostic value than HRV parameters in patients with chronic HF. The combination of abnormal WR and n-VLFP would be useful to identify chronic HF patients at a higher risk of cardiac events.

Prognostic significance of cardiac 123I metaiodobenzylguanidine imaging for mortality and morbidity in patients with chronic heart failure: a prospective study

OBJECTIVE To determine whether cardiac iodine-123 metaiodobenzylguanidine (123I MIBG) imaging is useful in predicting the prognosis of patients with chronic heart failure. DESIGN Cardiac 123I MIBG imaging was done on entry to the study. The cardiac MIBG washout rate was calculated from anterior chest view images obtained 20 and 200 minutes after injection of the isotope. Study patients were divided into two groups with washout rates above and below 27% (the mean value + 2 SD obtained in 20 normal subjects), and were then followed up. SETTING Tertiary referral centre. PATIENTS 79 patients with chronic heart failure in whom the left ventricular ejection fraction was less than 40%. RESULTS There were 37 patients in group 1 (washout rate of ⩾ 27%) and 42 in group 2 (< 27%). During a follow up period of between 1 and 52 months, eight patients died suddenly and five died of worsening heart failure in group 1, while none died in group 2; 13 patients in group 1 and four in group 2 were admitted to hospital for progressive heart failure. Kaplan–Meier analysis showed that group 1 had a significantly higher mortality and morbidity (p = 0.001 and p < 0.001, respectively) than group 2. CONCLUSIONS Cardiac 123I MIBG washout rate seems to be a good predictor of prognosis in patients with chronic heart failure.

Prediction of paroxysmal atrial fibrillation in patients with congestive heart failure : A prospective study

OBJECTIVES We sought to prospectively determine whether patients with congestive heart failure (CHF) at risk for paroxysmal atrial fibrillation (PAF) could be identified by clinical and study variables including the P-wave signal-averaged electrocardiogram (P-SAECG). BACKGROUND Although it is important to assess the risk of developing PAF in patients with CHF, it still remains difficult to predict the PAF appearance in patients with CHF clinically. METHODS The study group consisted of 75 patients in sinus rhythm without a history of PAF, whose left ventricular ejection fraction, as measured by radionuclide angiography, was <40%. These patients underwent P-SAECG, echocardiography and 24-h Holter monitoring; in addition, the plasma concentration of atrial natriuretic peptide (ANP) was measured at study entry. RESULTS An abnormal P-SAECG was found at study entry in 29 of 75 patients. In the follow-up period of 21 +/- 9 months, the PAF attacks documented on the ECG significantly more frequently occurred in patients with (32%) rather than without an abnormal P-SAECG (2%) (p = 0.0002). The plasma ANP level was significantly higher in patients with rather than without PAF attacks (75 +/- 41 vs. 54 +/- 60 pg/ml, p = 0.01), although there were no significant differences in age, left atrial dimension or high grade atrial premature beats between the groups. The multivariate Cox analysis identified that the variables significantly associated with PAF development were an abnormal P-SAECG (hazard ratio 19.1, p = 0.0069) and elevated ANP level > or =60 pg/ml (hazard ratio 8.6, p = 0.018). CONCLUSIONS An abnormal P-SAECG and elevated ANP level could be predictors of PAF development in patients with CHF.

Increased expression of P-selectin on platelets is a risk factor for silent cerebral infarction in patients with atrial fibrillation : Role of nitric oxide

BACKGROUND Platelet activation and decreased levels of nitrite and nitrate (NOx), stable end products of nitric oxide (NO), are reported in patients with atrial fibrillation (AF). We examined the time-course changes in plasma NOx levels and the expression of P-selectin on platelets after the onset of AF in a canine model and determined whether these parameters could be risk factors for silent cerebral infarction in patients with AF. METHODS AND RESULTS AF was induced by rapid atrial pacing in the canine model of AF. Plasma NOx levels were significantly decreased and the levels of P-selectin on platelets and of neutrophil/platelet conjugates were significantly increased after the onset of AF in this model. The in vitro experiments demonstrated that the inhibition of NO synthesis increased the expression of P-selectin on platelets. Plasma NOx levels (19.7+/-2.4 versus 27.5+/-2.8 micromol/L) were significantly lower in 25 patients with AF compared with age- (+/-2 years) and sex-matched control subjects. Conversely, the levels of P-selectin on platelets (7.6+/-0.8% versus 4.8+/-0.7%) and of neutrophil/platelet conjugates (14.8+/-0.9% versus 8.1+/-0.6%) were significantly higher in patients with AF. Multiple regression analysis revealed that increased P-selectin on platelets and advanced age were associated with the number of foci of silent cerebral infarction. CONCLUSIONS An irregular heart rate that is characteristic of AF appeared to blunt NO synthesis. The increased expression of P-selectin on platelets associated with the reduced NO levels was a risk factor for silent cerebral infarction in patients with AF.

Prediction of Transition to Chronic Atrial Fibrillation in Patients With Paroxysmal Atrial Fibrillation by Signal- Averaged Electrocardiography A Prospective Study

BACKGROUND It is well known that paroxysmal atrial fibrillation (PAF) often precedes the establishment of chronic atrial fibrillation (CAF). However, there have been no definite methods to predict the transition from PAF to CAF. The purpose of this report was to determine prospectively whether P-wave-triggered signal-averaged ECG (P-SAE) is useful for the prediction of the transition to CAF in patients with PAF. METHODS AND RESULTS One hundred twenty-two consecutive patients with PAF were prospectively followed after P-SAE, echocardiography, and 24-hour Holter monitoring at study entry. The duration (Ad) and root-mean-square voltage for the last 30 ms (LP30) of the filtered P wave were measured in P-SAE. The abnormality of P-SAE for the prediction of transition to CAF was defined as Ad > or = 145 ms and LP30 < 3.0 microV. Twenty-three (19%; group 1) of the patients had the abnormality of P-SAE, whereas the others (group 2) did not. During the follow-up period (mean, 26+/-12 months), 10 patients (43%) in group 1 acquired CAF, whereas the transition to CAF was observed in only 4 patients (4%) in group 2. Kaplan-Meier analysis revealed that the transition to CAF was significantly observed more often in group 1 than in group 2 (log-rank test, P<.0001). The Cox proportional hazards regression model identified that the variables most significantly associated with the transition to CAF were Ad (chi2=8.6, P=.003) and LP30 (chi2=5.1, P=.02), although significant differences in the left atrial dimension (40.8+/-5.3 versus 37.3+/-5.5 mm, P<.01) and the number of atrial premature contractions (3641+/-4524 versus 1489+/-2895 beats/d, P<.05) were observed between groups 1 and 2. CONCLUSIONS These results indicate that P-SAE could be useful to identify patients at risk for the transition from PAF to CAF.

Which subgroup of patients with dilated cardiomyopathy would benefit from long-term beta-blocker therapy ? A histologic viewpoint

OBJECTIVES The purpose of this study was to elucidate whether the effectiveness of long-term beta-blocker therapy could be predicted before this therapy is started. BACKGROUND Long-term beta-blocker therapy has recently been reported to provide a favorable effect in treatment of congestive heart failure due to dilated cardiomyopathy. METHODS Several measurements including histologic variables before administration of metoprolol were retrospectively compared among 18 good responders (showing improvement of at least one New York Heart Association functional class or an increase in ejection fraction > or = 0.10 12 months after drug administration) and 12 poor responders without such improvement. RESULTS Although there were no significant differences between the two groups in age, gender, functional class, heart rate, blood pressure, pulmonary capillary wedge pressure, cardiac index, left ventricular end-diastolic dimension and ejection fraction, percent fibrosis estimated by the point-counting method in endomyocardial biopsy specimens was significantly lower in good than in poor responders (7.6 +/- 5.7 vs. 14.2 +/- 9.7%, p < 0.05). Moreover, when the types of fibrosis were classified as interfascicular and intercellular by the dominance of counted points, there were 13 cases of interfascicular fibrosis and 5 cases of intercellular fibrosis in good responders and 1 case of interfascicular fibrosis and 11 cases of intercellular fibrosis in poor responders (p < 0.001, sensitivity 72%, specificity 91%, predictive accuracy 80%). These results suggest that improvement with long-term beta-blocker therapy may be more likely to occur in patients with less myocardial fibrosis, with interfascicular fibrosis the dominant type. CONCLUSIONS The extent and type of fibrosis may be important factors in the prediction of the effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy.

Prediction of sudden death in patients with mild-to-moderate chronic heart failure by using cardiac iodine-123 metaiodobenzylguanidine imaging

Objective: To evaluate the usefulness of cardiac iodine-123 (123I) metaiodobenzylguanidine (MIBG) imaging as a predictor of sudden death in patients with chronic heart failure (CHF). Design and setting: Prospective cohort study in a tertiary referral centre. Patients: 97 outpatients with CHF with a radionuclide left ventricular ejection fraction <40% (mean (SD) 29% (7.5%)). Interventions: At study entry, cardiac I-123 MIBG imaging was performed. The cardiac MIBG heart-to-mediastinum ratio (H/M) and washout rate (WR) were obtained from MIBG imaging. Main outcome measures: Patients were assigned to two groups based upon 27% of WR, which was the mean (2SD) control WR. 48 of 97 patients with CHF had abnormal WR (⩾27%), whereas the remaining 49 patients had normal WR (<27%). All the study patients were then followed up. Results: During the mean (SD) follow-up period of 65 (29) months, 12 (25%) patients in the abnormal WR group and 2 (4%) patients in the normal WR group died suddenly. Kaplan–Meier analysis revealed that sudden death was more often observed in patients with abnormal WR than those with normal WR (p = 0.001). On Cox regression analysis, MIBG WR, H/M on the delayed image and H/M on the early image were significantly associated with sudden death. Conclusion: Cardiac MIBG imaging would be useful for predicting sudden death in patients with CHF.