Kaoru Tanno

Microvolt T-Wave Alternans as a Predictor of Ventricular Tachyarrhythmias A Prospective Study Using Atrial Pacing

Background—Microvolt T-wave alternans (TWA) is reported to be closely associated with sudden cardiac death (SCD) and ventricular tachycardia (VT). Animal experiments revealed that microvolt TWA is highly dependent on heart rate. The purpose of this study was to determine whether patients with TWA at relatively low heart rates have increased vulnerability to ventricular tachyarrhythmias. Methods and Results—Subjects were 248 consecutive patients (158 men, 90 women; mean age, 59±17 years) who underwent electrophysiological study from 1997 to 2000. TWA recording was made in sinus rhythm and at atrial pacing rates of 90, 100, 110, and 120 bpm with the Cambridge Heart CH2000 system. Alternans voltage (Valt) was measured when the alternans ratio was >3 for a period of >1 minute in VM, X, Y, Z, or 2 adjacent precordial leads. Study end point was the first appearance of VT, ventricular fibrillation (VF), appropriate implantable cardioverter-defibrillator therapy with pacing or shocks, or SCD. During the 37±12-month follow-up period, 22 patients had sustained VT, and 5 patients died of SCD. In patients with >1.9-μV Valt at rates of 90, 100, and 110 bpm, the incidence of VT/VF/SCD was 56%, 28%, and 18%, respectively. Valt of >2.9 μV at a heart rate of 90 bpm had a 70% positive predictive value for VT/VF/SCD. However, when Valt was <0.9 μV at a rate of 120 bpm, negative predictive value was 100%. Conclusions—Patients with TWA at relatively low heart rates are susceptible to ventricular tachyarrhythmias.

Prolonged Paced QRS Duration as a Predictor for Congestive Heart Failure in Patients with Right Ventricular Apical Pacing

Background: The recent studies showed that right ventricular (RV) pacing was associated with worsening of heart failure. The aim of this study is to clarify the clinical significance of paced QRS duration during RV pacing to predict congestive heart failure (CHF) patients.

Association Between Left and Right Atrial Remodeling With Atrial Fibrillation Recurrence After Pulmonary Vein Catheter Ablation in Patients With Paroxysmal Atrial Fibrillation A Pilot Study

Background— Left atrial (LA) remodeling is a factor in atrial fibrillation (AF) recurrence after pulmonary vein catheter ablation (CA), but right atrium (RA) remodeling has not been investigated for possible associations to AF recurrence. Methods and Results— Using 64-slice multidetector computed tomography, RA and LA volumes were measured 3-dimensionally before CA in 65 patients with initially proven idiopathic paroxysmal AF (mean age, 60±10 years, 81.5% men). The CA procedure was guided by CARTO Merge atrial electroanatomic mapping. Sixteen patients (24.6%) had AF recurrence within the 6-month period after the CA. The recurrence was associated with a large RA volume [odds ratio, 1.04; 95% confidence interval (CI), 1.02 to 1.07, P<0.0001], a large LA volume with 1.04 [95% CI, 1.01 to 1.06, P=0.002], and low LA mean voltage with 1.03 [95% CI, 1.01 to 1.05, P=0.002]. After adjustment for potential confounding variables, RA and LA volumes remained predictive of AF recurrence. Large atrial volumes (mL) (RA ≥87 or LA ≥99) predicted AF recurrence (sensitivity of RA volume: 81.3% in 13 of 16 patients with AF recurrence; specificity: 75.5% in 37 of 49 patients without AF recurrence; sensitivity of LA volume: 81.3% in 13 of 16 patients with AF recurrence; specificity: 69.4% in 34 of 49 patients without AF recurrence), and the combined estimate of both atrial volumes was incremental and additive prognostic power (sensitivity: 75% in 12 of 16 patients with AF recurrence; specificity: 93.9% in 46 of 49 patients without AF recurrence). Conclusions— Both LA and RA remodeling are equally associated with post-CA AF recurrence.

The Significance of Cardiac Sympathetic Nervous System Abnormality in the Long-Term Prognosis of Patients with a History of Ventricular Tachyarrhythmia

Severe left ventricular dysfunction or cardiac sympathetic nervous system (SNS) abnormality predicts cardiac death in various heart diseases, including arrhythmogenic disorders. However, it is not clear whether SNS abnormality predicts sudden cardiac death during long-term follow-up in patients with a history of ventricular tachyarrhythmia. We hypothesized that SNS abnormality would be associated with recurrent ventricular arrhythmic events. Methods: 123I-metaiodobenzylguanidine (MIBG) scintigraphy was performed on 86 patients (mean age ± SD, 46 ± 19 y, 65.1% men) with a history of ventricular tachycardia or fibrillation. 123I-MIBG (111 MBq) was intravenously administered under resting conditions, and planar images were obtained 15 min and 4 h later (anterior view for 6 min; 512 × 512 matrices; zoom ratio, 1.0). SNS activity was assessed using the heart-to-mediastinum ratio on delayed imaging. Results: During about 11 y of follow-up (mean ± SD, 5.2 ± 3.7 y), 3 patients (3.5%) had sudden cardiac death and 21 patients (24.4%) had sustained ventricular tachyarrhythmic events. SNS abnormality, defined as a heart-to-mediastinum ratio of less than 2.8, and left ventricular dysfunction, defined as a left ventricular ejection fraction of less than 50%, were associated with sudden cardiac death or recurrent ventricular tachyarrhythmic events (18/40 patients [45%] with SNS abnormality, vs. 6/46 patients [13%] without, P = 0.004; 9/15 patients [60%] with left ventricular dysfunction, vs. 15/71 patients [21.1%] without, P = 0.008). After adjustment for potential confounding variables such as age, sex, coronary risk factors, medication use, history of structural heart disease, and left ventricular function, SNS abnormality was a powerful predictor of recurrent arrhythmic events, with a hazard ratio of 3.6 [95% confidence interval, 1.4–9.2, P = 0.007]). Further, SNS abnormality had incremental and additive prognostic power in combination with left ventricular dysfunction, with an adjusted hazard ratio of 4.4 [95% confidence interval, 1.9–9.9, P < 0.0001]). Conclusion: SNS abnormality predicted recurrent ventricular tachyarrhythmic events during long-term follow-up. 123I-MIBG scintigraphic evaluations for SNS abnormality may be an option for screening patients at high risk for sudden cardiac death.

Sustained Left Ventricular Tachycardia Terminated by Dipyridamole: Cyclic AMPMediated Triggered Activity as a Possible Mechanism

Sustained VT in two patients was terminated by intravenous administration of dipyridamole, an adenosine transport inhibitor. VT was induced by rapid atrial or ventricular pacing, isoproterenol, or dibutyryl cyclic AMP infusion, or exercise. VT also was aborted by adenosine triphosphate or acetylcholine injection, or by vagal stimulation. VT was terminated or prevented by verapamil or propranolol. In addition, arrhythmias were prevented by oral administration of dipyridamole. These results suggest that VT is due to cyclic AMP‐mediated triggered activity and that inhibition by dipyridamole may be due to a reduction in the intracellular concentration of cyclic AMP.

Candesartan decreases type III procollagen-N-peptide levels and inflammatory marker levels and maintains sinus rhythm in patients with atrial fibrillation.

This study has evaluated whether candesartans prevent the recurrence of atrial fibrillation (AF) and decrease type III procollagen-N-peptide (PIIINP) levels. A total of 153 patients with AF were enrolled in this study. Three groups of patients were compared; candesartan group was treated with candesartan plus bepridil (n = 52); and carvedilol group with carvedilol plus bepridil (n = 51); and bepridil group with bepridil alone (n = 50). The primary end point was length of time to the recurrence of AF and all patients were ultimately followed-up for 730 days. Serum levels of the biomarkers were measured at baseline and after 24 months. Maintenance of sinus rhythm was achieved in 25 (50%) patients in bepridil group, 37 (73%) in candesartan group, and 34 (67%) in carvedilol group, giving a bepridil group/candesartan group hazard ratio of 0.36 (95% confidence interval 0.21-0.63; P = 0.03). Candesartan significantly decreased PIIINP levels at 24 months than at baseline in sinus rhythm group (0.57 ± 0.02 vs. 0.64 ± 0.05 U/mL, P = 0.04) and did not decrease PIIINP levels in the recurrence group. In conclusions, PIIINP might be related to the possibility of the atrial fibrosis for AF. However, further studies are needed to clarify the relationship between PIIINP and AF.

Effects of nicorandil, a potassium channel opener, on idiopathic ventricular tachycardia.

OBJECTIVES We assessed the effects of the adenosine triphosphate (ATP)-sensitive potassium channel opener, nicorandil, on ATP- and verapamil-responsive ventricular tachycardias (VTs). BACKGROUND Adenosine- or ATP-sensitive VTs are thought to be due to a nonreentrant mechanism, presumably delayed afterdepolarization. We suggest that this potassium channel opener may suppress ATP- and verapamil-sensitive VTs. METHOD The subjects included 13 patients with idiopathic VTs, 7 of whom had sustained VT and 6 of whom had nonsustained VT. We evaluated the effects of ATP, nicorandil and verapamil on VTs. RESULTS Sustained VT: Verapamil had preventive effects on seven VTs. Four VTs were terminated by ATP, and of these, nicorandil terminated two and prevented exercise-induced VT in the two others. Three ATP-insensitive VTs, which were determined to be due to a reentry by an electrophysiologic study, were not terminated by nicorandil. Nonsustained VT: All six VTs were inhibited by ATP, and five of these were suppressed by nicorandil. Verapamil inhibited four of the five VTs. QT intervals and the corrected QT intervals were significantly shortened by nicorandil. CONCLUSIONS Nicorandil suppresses ATP- and verapamil-responsive VTs. One of the mechanisms of suppression by nicorandil might be related to a reduction of calcium in the myocardium, because it reduces the action potential duration.

Iodine-123 mIBG Imaging for Predicting the Development of Atrial Fibrillation

OBJECTIVES we investigated whether cardiac sympathetic nervous system (SNS) activity measured by iodine-123 meta-iodobenzylguanidine ((123)I-mIBG) imaging would be associated with both the occurrence of heart failure (HF) and the transit to permanent atrial fibrillation (AF) in patients with paroxysmal AF. BACKGROUND atrial fibrillation occurs suddenly and transiently and can persist, and results in the occurrence of HF. An important feature of AF and HF is their propensity to coexist not only because they share antecedent risk factors, but also because the one may directly predispose the heart to the other. However, a useful modality for predicting the occurrences of both those has not been established in patients with paroxysmal AF. METHODS the (123)I-mIBG scintigraphy was performed to evaluate cardiac SNS activity presented as the heart/mediastinum ratio in 98 consecutive patients (age 66 ± 13 years, 63.3% male) with idiopathic paroxysmal AF and preserved left ventricular ejection fraction (≥ 50%). RESULTS during 4 ± 3.6 years of follow-up, the transit to permanent AF was associated with the occurrence of HF (34.3% in 12 of 35 patients with permanent AF vs. 6.3% in 4 of 63 patients without, p < 0.0001). Lower heart/mediastinum ratio and lower left ventricular ejection fraction were the independent predictors of the transit to permanent AF with adjusted hazard ratios of 3.44 (95% confidence interval [CI]: 1.9 to 6.2, p < 0.0001) and 1.04 (95% CI: 1.01 to 1.08, p = 0.014). Further, these factors and higher plasma brain natriuretic peptide concentration were the independent predictors of the occurrence of HF with permanent AF, with adjusted hazard ratios of 5.08 (95% CI: 1.5 to 17.5, p = 0.011), 1.11 (95% CI: 1.03 to 1.19, p = 0.004), and 1.004 (95% CI: 1.001 to 1.008, p = 0.014). CONCLUSIONS cardiac SNS abnormality was associated with the occurrence of both HF and permanent AF in paroxysmal AF patients, and (123)I-mIBG imaging may be a useful modality for predicting the development of AF.

Onset heart rate and microvolt t-wave alternans during atrial pacing.

patient subgroup based on our a priori suspicion that these patients would benefit from an ICD and based on their high risk for death. These data, however, suggest that patients with severe heart failure should be considered for randomized trials, similar to patients with functional class II and III congestive heart failure. This risk for death may be reduced similarly in the functional class IV heart failure patients, but these patients, especially those with a history of ventricular arrhythmias, will remain a high-risk group, and will continue to be at risk for several forms of sudden death, including bradyarrhythmic and tachyarrhythmic death. It is possible that some patients did benefit from the ICD based on its backup bradycardia pacing capabilities. Although this cannot be excluded, it could still indicate the potential benefits of the ICD. These data indicate that early death is not inevitable in patients with functional class IV heart failure with malignant ventricular arrhythmias and an ICD implant. Important selection biases cannot be excluded. Patients who appeared to stabilize on medical therapy were more likely to be included. Exclusion of patients with functional class IV heart failure from future arrhythmia trials should be reconsidered.

Type III procollagen-N-peptide as a predictor of persistent atrial fibrillation recurrence after cardioversion.

AIMS Fibrosis and inflammation may play a significant role in the pathogenesis of atrial fibrillation (AF) recurrence. Type III procollagen-N-peptide (PIIINP) may be related to atrial fibrosis and play a role in predicting the recurrence of AF. We investigated whether PIIINP as a fibrosis marker predicts the recurrence of AF after cardioversion. METHODS AND RESULTS Serum PIIINP, interleukin-6, high-sensitivity C-reactive protein, brain natriuretic peptide, renin and aldosterone were measured at baseline and 24 months in 88 patients (62%) with sinus rhythm (SR) maintenance and 54 patients (38%) with AF recurrence. Furthermore, the root mean square voltage in the last 20 ms (RMS20) via P-wave signal-averaged electrocardiogram (P-SAECG) was measured and the relationship between fibrosis biomarkers and RMS20 was examined. Baseline PIIINP with AF recurrence was significantly higher than for those with SR maintenance (0.664 vs. 0.581 U/mL, P = 0.001). However, there were no significant differences in other biomarkers. A logistic regression identified PIIINP (odds ratio 2.61, P = 0.008) as an independent predictor of AF recurrence. The RMS20 as measured by P-SAECG with SR maintenance and PIIINP levels <0.72 U/mL (at baseline) was significantly higher after 24 months than at baseline. Furthermore, the RMS20 with AF recurrence and PIIINP levels >0.72 U/mL (at baseline) was significantly lower after 24 months than baseline. CONCLUSIONS Elevated baseline PIIINP concentration is an independent predictor for AF recurrence after cardioversion. Furthermore, there is a relationship between PIIINP and RMS20 and the fibrosis of AF.