T-wave alternans (TWA) is a useful method for evaluating repolarization abnormalities and as a predictor of life-threatening ventricular arrhythmias. Although life-threatening ventricular arrhythmias are occasionally observed during ischemic attacks in patients with vasospastic angina (VSA), there have been no studies to detect repolarization abnormalities using TWA analysis in these patients during the asymptomatic phase. The aim of this study was to analyze modified moving average (MMA) TWA using Holter recordings in 40 patients with VSA and in 40 control subjects. The incidence of positive TWA was higher in the VSA group than in the control group (24 of 40 [60%] vs 0 of 40 [0%], p <0.01). The value of the maximum MMA TWA was also greater in the VSA group than in the control group (68.6 ± 21 vs 34.0 ± 11 μV, p <0.01). In the VSA group, although there was no significant difference in maximum MMA TWA values between patients with multiple- and single-vessel spasm, patients with ventricular tachycardias had higher values than those without (83.0 ± 15 vs 65.9 ± 20 μV, p <0.05). Patients taking calcium channel blockers exhibited decreased values of maximum MMA TWA compared with subjects not taking these drugs (73.8 ± 18 vs 59.5 ± 21 μV, p <0.05). In conclusion, high values and incidences of TWA events were observed in patients with VSA. In the VSA group, maximum values of MMA TWA were high in patients with ventricular tachycardias but decreased in those taking calcium channel blockers. The results suggest that the patients with VSA during asymptomatic phases exhibit repolarization abnormalities leading to a potential risk for life-threatening arrhythmias.
Vasospastic angina (VSA) is caused by coronary artery spasm and results in severe chest pain, usually without physical or emotional stress and with concurrent electrocardiographic findings of transient ST-segment elevation. Malignant ventricular tachyarrhythmias (tachycardia and fibrillation) and complete atrioventricular block have been repeatedly observed during ischemic attacks caused by spasm. Recently, a study in a large cohort demonstrated 35 survivors of out-of-hospital cardiac arrest among 1,429 patients with VSA. Follow-up in patients with out-of-hospital cardiac arrest with implantable cardioverter-defibrillators revealed 2 recurrent cases of ventricular fibrillation. In a retrospective observational study, we found 23 patients with implantable cardioverter-defibrillators because of documented ventricular arrhythmia and VSA. During 2.9-year follow-up, 5 patients reached end points, including 4 patients with appropriate therapy from implantable cardioverter-defibrillators and 1 patient with pulseless electrical activity. Therefore, patients with VSA have a potential substrate for malignant ventricular tachyarrhythmias. As to the repolarization abnormality in patients with VSA, the level and morphology of ST-segment elevation during episodes of coronary spasm spontaneously fluctuate over time and occasionally exhibit circadian variation. In previous studies, we reported increased QT dispersion in patients with VSA, even during the asymptomatic period, while increased QT dispersion is assumed as a measure to represent inhomogeneity of ventricular repolarization, resulting in susceptibility to ventricular arrhythmias. Because modified moving average (MMA) T-wave alternans (TWA) analysis has been shown to be superior measure to QT dispersion measurement for predicting a high risk for ventricular tachyarrhythmia and sudden cardiac death, the present study was performed to detect repolarization abnormalities using MMA TWA in patients with VSA during the asymptomatic period.
Methods
We performed a retrospective analysis of 80 subjects who underwent 24-hour Holter monitoring outside the hospital from July 2005 to December 2010 at the Yokohama Minami Kyosai Hospital. Of the 80 subjects, we studied 40 consecutive patients with VSA (18 men and 22 women, mean age 59 ± 15 years). All patients with VSA were diagnosed by documentation of spontaneous episodes of chest pain with concomitant ischemic ST-segment changes on electrocardiography and coronary vasospasm by coronary angiography with chest pain and/or electrocardiographic changes by intracoronary injection of acetylcholine. Coronary vasospasm was defined as total or subtotal (99% with delay) occlusion of the vessel. The control group consisted of 40 patients selected to match the age and gender distribution of the VSA group (18 men and 22 women, mean age 59 ± 13 years). None of these patients exhibited supraventricular or ventricular tachycardias or ischemic ST-segment changes on Holter monitoring or rest 12-lead electrocardiography. No patients had positive exercise test results for ischemia. Of 40 patients with VSA, 15 patients took calcium channel blockers (CCBs), including diltiazem (9 patients) and nifedipine (7 patients).
Neither group had a history of myocardial infarction or signs of cardiomyopathy, valvular heart disease, or congestive heart disease. None of the study subjects had any abnormal findings on 2-dimensional transthoracic echocardiography or Doppler echocardiography.
Risk factors included smoking, hypertension, diabetes mellitus, and dyslipidemia. The study protocol was approved by the ethics committee at the Yokohama Minami Kyosai Hospital, and written informed consent was obtained from each subject.
We analyzed TWA from 2 channel records (lead V 1 , NASA; lead V 5 , CM5) by ambulatory Holter monitoring using MARS PC version 7.03 (GE Healthcare, Milwaukee, Wisconsin) and identified periods of possible TWA by applying an MMA. MMA is a time-domain-based method that bifurcates the beat stream and generates a separate moving average template (ABABABAB). Average values were updated by a weighting factor of 1/8 the difference between the ongoing average and the current pair of beats. A noise level of 20 μV was adopted in the system configuration. Manual editing was performed if the data were not eligible for analysis because of artifacts or noise. The maximum TWA value was defined as the highest value of TWA in either channel. Positive TWA was defined as TWA values >65 μV, according to previous reports. Ventricular tachycardia was defined as a rapid run of >3 consecutive premature ventricular contractions.
Analysis of MMA-based TWA was performed using MARS PC version 7.03. Data are expressed as mean ± SD. Two-tailed unpaired Student’s t tests were used for comparison of the group mean values expressed as continuous variables. Chi-square tests were used to evaluate differences in categorical variables between groups. To evaluate the effect of high TWA levels on the risk for coronary spasm or ventricular arrhythmias, we used standard analysis methods of case-control data and logistic regression models to estimate the odds ratio as a measure of relative risk. For analysis, we used univariate and multivariate models that controlled for the effects of TWA (65-μV cut point), age, gender, smoking, hypertension, dyslipidemia, diabetes mellitus, the left ventricular ejection fraction, and CCB use. A p value <0.05 was considered significant. SPSS version 10.0 (SPSS, Inc., Chicago, Illinois) was used for statistical analysis. The corresponding values of parameters using a TWA cut-off point of 65 μV are presented for the incidence of ventricular tachycardia.
Results
There were no significant differences in baseline characteristics except CCB use between the VSA and control groups ( Table 1 ). The mean left ventricular ejection fraction on echocardiography in the VSA group was comparable to that in the control (66.2 ± 15% vs 71.0 ± 11%). In the VSA group, vasospasm of multiple coronary arteries was induced by acetylcholine injection in 15 of 40 patients (37.5%), and single coronary artery spasm was present in the remaining 25 patients. Fifteen patients (37.5%) were taking CCBs during ambulatory Holter monitoring.
| Parameter | Control Group | VSA Group | p Value |
|---|---|---|---|
| (n = 40) | (n = 40) | ||
| Men/women | 17/23 | 19/21 | 0.65 |
| Age (years) | 59 ± 15 | 59 ± 13 | 0.31 |
| Smokers | 10 (25%) | 14 (35%) | 0.33 |
| Hypertension ⁎ | 10 (25%) | 13 (33%) | 0.45 |
| Dyslipidemia † | 14 (35%) | 16 (40%) | 0.64 |
| Diabetes mellitus ‡ | 6 (15%) | 4 (10%) | 0.50 |
| Left ventricular ejection fraction (%) | 71 ± 11 | 66 ± 15 | 0.05 |
| CCB use | 0 (0%) | 15(38%) | <0.001 |
⁎ Systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg.
† Low-density lipoprotein cholesterol level>140 mg/dl or triglyceride level >150 mg/dl.
‡ Morning fasting glucose level ≥126 mg/dl, glycosylated hemoglobin >6.5%, or use of medical therapy, including insulin.
The VSA group had a higher incidence of positive TWA than the control group (24 of 40 patients [60.0%] vs 0 of 40 patients [0%], p <0.01; Figure 1 ). Figure 2 presents an interesting case demonstrating TWA in a patient in the VSA group. This patient developed multiple vasospasm induced by acetylcholine injection together with chest pain. A Holter recording during the asymptomatic period demonstrated macroscopic spontaneous TWA without chest pain and ischemic ST-segment elevation in the NASA lead. No macroscopic TWA was observed in the remaining patients in the VSA group. Nonsustained ventricular tachycardia was observed in 6 of 40 patients with VSA during Holter recording.
The mean value of maximum MMA TWA was greater in the VSA group than in the control group (68.6 ± 21 vs 34.0 ± 11 μV, p <0.01; Figure 3 ). There was no significant difference in maximum MMA TWA between patients with multivessel spasm and single-vessel spasm by coronary angiography (70.3 ± 18 vs 66.1 ± 19 μV), but the value was significantly lower in patients taking CCBs than in those not taking CCBs (59.5 ± 21 vs 73.8 ± 18 μV, p <0.05; Figure 4 ). Furthermore, patients showing nonsustained ventricular tachycardia during Holter recording exhibited a higher mean value of maximum MMA TWA compared to those without tachycardia (83.0 ± 15 vs 65.9 ± 20 μV, p <0.05; Figure 5 ).
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
