Quantitative assessment of cibenzoline administration for vagally mediated paroxysmal atrial fibrillation using frequency-domain heart rate variability analysis.

BACKGROUND: Cibenzoline (CBZ), a class I antiarrhythmic drug, has been widely used to maintain sinus rhythm in patients with paroxysmal atrial fibrillation (P-AF). This agent has an anticholinergic action and will become the drug of first choice for vagally mediated P-AF. We assessed its efficacy quantitatively by analyzing the frequency-domain heart rate variability (FD-HRV) of the Holter electrocardiogram (ECG) in patients with vagal P-AF. METHODS: We enrolled 65 consecutive patients with vagal P-AF, but 31 patients were excluded because of the occurrence of significant arrhythmias during the 24-h Holter recordings. Accordingly, CBZ was administered to the remaining 34 patients. After administration, a Holter ECG recording was made again. High frequency (HF) components, i.e., vagal tone index, on the FD-HRV analysis from 00:00 h to 06:00 h were used for assessment. In 14 patients, the treatment was changed to disopyramide (DSP) and the same analyses were performed. RESULTS: In two patients, the FD-HRV analysis was not utilized after administration. Finally, 32 patients were available for evaluation. CBZ was considered effective for vagal P-AF in 24 patients (75%). After administration, the HF component levels decreased (1589+/-795 ms(2) vs. 850+/-524 ms(2), p<0.0001). Comparison of the pre-administration HF component levels between the CBZ-responsive group and the CBZ-non-responsive group showed higher levels in the CBZ-responsive group (1766+/-758 ms(2) vs. 1058+/-690 ms(2), p=0.026). Although no significant difference in the reduction of the HF component levels was found between CBZ and DSP, DSP had anticholinergic side effects in two patients (14%). CONCLUSIONS: In vagal P-AF patients, larger HF components on the FD-HRV analysis could be a hallmark of the antiarrhythmic action of CBZ. The reduction in the HF component levels after drug administration is useful for a quantitative assessment of anticholinergic action.

Time-domain T-wave alternans measured from Holter electrocardiograms predicts cardiac mortality in patients with left ventricular dysfunction: a prospective study.

BACKGROUND: Time-domain T-wave alternans (TWA) is useful for identifying patients at risk for serious events after myocardial infarction. OBJECTIVE: The purpose of this study was to prospectively evaluate the utility of time-domain TWA measured from Holter ECGs in predicting cardiac mortality in patients with left ventricular (LV) dysfunction. METHODS: Two hundred ninety-five consecutive patients with LV dysfunction were enrolled in the study. Patients were divided into two groups: the ischemic group (n = 195) and the nonischemic group (n = 100). Time-domain TWA was assessed using the modified moving average method from routine 24-hour Holter ECGs recorded during daily activity. The maximal time-domain TWA voltage at heart rate or=65 microV. The primary end-point was defined as cardiac mortality. RESULTS: Mean maximal time-domain TWA voltage was 54 +/- 16 microV. During follow-up of 390 +/- 212 days, 27 patients (17 in the ischemic group and 10 in the nonischemic group) died of cardiac causes. Fifty-three patients (18%) were time-domain TWA positive and 242 (82%) were time-domain TWA negative. Univariate Cox proportional hazards analyses revealed that older age, New York Heart Association functional class III or IV, diabetes, renal dysfunction, nonsustained ventricular tachycardia, and time-domain TWA were associated with cardiac mortality. In multivariate analysis, time-domain TWA had the most significant value (hazard ratio = 17.1, P <.0001). This index also was significant in both subgroups (ischemic group: hazard ratio = 19.0, P <.0001; nonischemic group: hazard ratio = 12.3, P = .002). CONCLUSION: Time-domain TWA measured from 24-hour Holter ECGs predicts cardiac mortality in patients with ischemic and nonischemic LV dysfunction.

Heart rate turbulence as a predictor of cardiac mortality and arrhythmic events in patients with dilated cardiomyopathy: a prospective study.

BACKGROUND: Few studies have described the clinical usefulness of heart rate turbulence (HRT), an autonomic predictor of mortality, in stratifying patients with dilated cardiomyopathy (DCM) at risk of cardiac mortality and arrhythmic events. We prospectively assessed the utility of HRT for risk stratification in patients with ischemic or nonischemic DCM. METHODS: We enrolled 375 consecutive patients with DCM including ischemic (n = 241) and nonischemic causes (n = 134). HRT was measured using an algorithm based on routine 24-hour Holter electrocardiograms, assessing 2 parameters: turbulence onset (TO) and turbulence slope (TS). HRT was considered positive when both TO was > or = 0% and TS was < or = 2.5 ms/R-R interval. The primary endpoint was defined as cardiac mortality and the secondary endpoint as occurrence of hemodynamically stable sustained ventricular tachyarrhythmias. RESULTS: Of patients enrolled, 83 patients (22.1%) were not utilized for HRT assessment because there were too few ventricular premature beats, or for other reasons. Eighty-one of 292 patients (27.7%) were HRT-positive. During follow-up of 445 +/- 216 days, 30 patients (10.3%) reached the primary endpoint and 17 patients, the secondary endpoint. The hazard ratio (HR) of patients with an HRT-positive outcome was 6.4 (95%CI, 3.0-14.1; P < 0.0001) for the primary endpoint and 5.1 (95%CI, 2.8-9.3; P < 0.0001) for combined endpoints. On subanalysis, HRT positivity was significantly associated in both the ischemic and nonischemic DCM patients with both the primary endpoint (HR = 4.9, P = 0.0006 and HR = 12.3, P = 0.002, respectively) and with combined endpoints. CONCLUSIONS: HRT is a powerful risk stratification marker for cardiac mortality and arrhythmic events in patients with DCM whether ischemia is present or not.