Clinical Relevance of Exercise-Induced Ventricular Arrhythmias in Suspected Coronary Artery Disease Mark A. Marieb, MD, George A. Belier, MD, Robert S. Gibson, MD, Bruce B. Lerman, MD, and Sanjiv Kaul, MD
Because there is controversy regarding the clinical refevance of exercise-hxiuced ventricular arrhythmias, we anafyxed their significance in 363 patients who had undergone both exercise thaiiium201 stress-testing and cardiac catheterization. Two-hundred twenty-one patients (58%) had no exercise-induced ventrieuiar arrhythmias while 162 (42%) did. There was no ditterenee between patients with and witbout exercise-hxfuced ventricular arrhythmias in terms of previous myocardiai infarction (p = 0.61), imidence of fixed thallium-201 defects (0.06), number of diseased vessels (p = 0.09) and resting feft ventriwfar ejection fraction (p = 0.06). in contrast, evidence of provocabfe ischemia (redistribution on thallium-201 and ST-segment depression on the electrocardiogram) were more iikefy (p 2 mm upsloping ST depression 0.08 ms after the J point in >2 contiguous leads in the presence of a normal baseline electrocardiogram; or, if there was an additicnal 22 mm ST-segment depression in patients with baseline ST-segment abnormalities as long as these were not associated with left bundle branch block, left ventricular hypertrophy or digitalis therapy. ’4 Thallium-201 imaging: The thallium-20 1 imaging protocol has been described previously.t5 Planar images were analyzed by 2 blinded observers by means of computer assistance using a previously described 7-segment model.15 Each of the 7 segments was classified as either normal or having a fixed or reversible defect. For this study, the presence of redistribution (partial or complete) was considered to represent exercise-induced ischemia.” Isolated washout abnormalities were not considered to represent ischemia.r6 Cardiac catheterization: Coronary artery disease was defined as either 250% or 170% luminal diameter narrowing of a major coronary artery or its major branch.17 The most severe stenosis was recorded for each vessel and patients were classified as having either no coronary artery disease or I-, 2- or 3-vessel or left main disease by both criteria.14 Left ventricular pressures were recorded and cineangiography was performed in 338 of the 383 patients. In these patients, wall motion was analyzed in the following 5 segments in the right anterior oblique view: anterobasal; anterolateral; apical; inferior and posterobasal. It was assessed as either normal or abnormal for each segment. Left ventricular ejection fraction was calculated using the modified Dodge equation.lx
Statistical anaiysis: Data were compiled on a minicomputer (VAX 8200, Digital Equipment Corporation) using RS/l (Bolt, Beranek, and Newman).t9 Continuous variables were expressed as mean f 1 standard deviation whereas categorical variables were expressed as proportions. Comparison of patients with and without exercise-induced ventricular arrhythmias was performed by means of either the t test with pooled variance (continuous variables) or the chi-square test (categorical variables). Differences between the 2 groups were considered statistically significant at p CO.05 (2-sided). To determine the variables independently associated with the presence of exercise-induced ventricular arrhythmias, multivariate analysis was performed by means of discriminant function analysis using BMDP (University of California at Los Angeles).20 Stepwise Cox regression analysis (BMDP) was performed to determine whether the occurrence of exercise-induced ventricular arrhythmias predicted adverse outcome (death, nonfatal myocardial infarction, and coronary revascularization after 3 months of cardiac catheterization).2’ The decision to perform revascularization in patients undergoing such a procedure within 3 months of cardiac catheterization and exercise testing could have been influenced by the results of these tests. Such patients, were, therefore, excluded from analysis. The survival of patients with and without exercise-induced ventricular arrhythmias was compared using the MantelCox test embodied in the life table analysis (Kaplan Meier) using BMDP.**
RESULTS
One-hundred sixty-two (42%) of the 383 patients had exercise-induced ventricular arrhythmias. Figure 1 shows the types of arrhythmias seen in these patients. One-hundred ninety-nine (52%) of the 383 patients had no ST depression on the exercise electrocardiogram, 85 (23%) had no defects on the initial thallium-201 images and 169 (44%) had no redistribution on the delayed thallium-201 images. Eighty-nine patients (23%) had no significant coronary artery disease when 250% luminal diameter narrowing was used as the criterion while 141 (37%) had no significant coronary artery disease when 270% stenosis was used as the criterion. Only 7 of the
No
V
Rare
arrhythmias
(5)
114) PVCs
(84)
PVCs (44)
(11) (2)
JULY 15, 1990
173
TABLE I Univariate Comparison of Clinical, Exercise and Electrocardiographic Variables in Patients With and Without Exercise-Induced Ventricular Arrhythmias EIVA
Variables
No EIVA
p Value
59i 10 91 65 49 59 12 1.8kO.8
57flO 82 64 43 67 10 1.7f0.8
0.006 0.02 0.91 0.61 0.09 0.50 0.38
55 1.1 f 1.2 2.4 f 2.7 2.0f 2.5 21
43 0.8f 1.03 1.8f2.0 1.3 f 2.0 15
0.02 0.008 0.04 0.004 0.14
Clinical Age (Y rs) % men % with typical angina % with previous Ml % on p blockers % on digitalis NYHA class Exercise variables % with ST dep Maximal ST dep (mm) No. leads with ST dep Duration of ST dep (min) % with horizontal or downsloping ST dep HR at peak exercise A HR rest - exercrse SBP at peak exercise A SBP rest -exercise Workload (METS) Duration of exercise (min) % with chest pain durtng exercise
128f26 53f21 158f26 28f22 5.9 f 2.6 6.0 f 2.7 19
127 f 26 54f23 154f27 28f24 6.4 f 2.8 6.3 f 2.8 21
Discrimination exercise-induced variate analysis:
0.56 0.74 0.17 0.88 0.10 0.29 0.73
dep = depression; EIVA = exercise-Induced ventrwlar arrhythmtas. HR = heart rate; AHR = change I” heart rate; MI = myocardlal Infarcton; NYHA = New York Heart Assoclatlon, SBP = systolic blood pressure; ASBP = change I” systolic blood pressure.
162 patients (4%) with exercise-induced ventricular arrhythmias did not have some abnormality on either the exercise electrocardiogram, thallium-201 images or the coronary angiogram compared to 33 of the 221 patients (15%) without these arrhythmias (p
Because there is controversy regarding the clinical refevance of exercise-hxiuced ventricular arrhythmias, we anafyxed their significance in 363 patients who had undergone both exercise thaiiium201 stress-testing and cardiac catheterization. Two-hundred twenty-one patients (58%) had no exercise-induced ventrieuiar arrhythmias while 162 (42%) did. There was no ditterenee between patients with and witbout exercise-hxfuced ventricular arrhythmias in terms of previous myocardiai infarction (p = 0.61), imidence of fixed thallium-201 defects (0.06), number of diseased vessels (p = 0.09) and resting feft ventriwfar ejection fraction (p = 0.06). in contrast, evidence of provocabfe ischemia (redistribution on thallium-201 and ST-segment depression on the electrocardiogram) were more iikefy (p 2 mm upsloping ST depression 0.08 ms after the J point in >2 contiguous leads in the presence of a normal baseline electrocardiogram; or, if there was an additicnal 22 mm ST-segment depression in patients with baseline ST-segment abnormalities as long as these were not associated with left bundle branch block, left ventricular hypertrophy or digitalis therapy. ’4 Thallium-201 imaging: The thallium-20 1 imaging protocol has been described previously.t5 Planar images were analyzed by 2 blinded observers by means of computer assistance using a previously described 7-segment model.15 Each of the 7 segments was classified as either normal or having a fixed or reversible defect. For this study, the presence of redistribution (partial or complete) was considered to represent exercise-induced ischemia.” Isolated washout abnormalities were not considered to represent ischemia.r6 Cardiac catheterization: Coronary artery disease was defined as either 250% or 170% luminal diameter narrowing of a major coronary artery or its major branch.17 The most severe stenosis was recorded for each vessel and patients were classified as having either no coronary artery disease or I-, 2- or 3-vessel or left main disease by both criteria.14 Left ventricular pressures were recorded and cineangiography was performed in 338 of the 383 patients. In these patients, wall motion was analyzed in the following 5 segments in the right anterior oblique view: anterobasal; anterolateral; apical; inferior and posterobasal. It was assessed as either normal or abnormal for each segment. Left ventricular ejection fraction was calculated using the modified Dodge equation.lx
Statistical anaiysis: Data were compiled on a minicomputer (VAX 8200, Digital Equipment Corporation) using RS/l (Bolt, Beranek, and Newman).t9 Continuous variables were expressed as mean f 1 standard deviation whereas categorical variables were expressed as proportions. Comparison of patients with and without exercise-induced ventricular arrhythmias was performed by means of either the t test with pooled variance (continuous variables) or the chi-square test (categorical variables). Differences between the 2 groups were considered statistically significant at p CO.05 (2-sided). To determine the variables independently associated with the presence of exercise-induced ventricular arrhythmias, multivariate analysis was performed by means of discriminant function analysis using BMDP (University of California at Los Angeles).20 Stepwise Cox regression analysis (BMDP) was performed to determine whether the occurrence of exercise-induced ventricular arrhythmias predicted adverse outcome (death, nonfatal myocardial infarction, and coronary revascularization after 3 months of cardiac catheterization).2’ The decision to perform revascularization in patients undergoing such a procedure within 3 months of cardiac catheterization and exercise testing could have been influenced by the results of these tests. Such patients, were, therefore, excluded from analysis. The survival of patients with and without exercise-induced ventricular arrhythmias was compared using the MantelCox test embodied in the life table analysis (Kaplan Meier) using BMDP.**
RESULTS
One-hundred sixty-two (42%) of the 383 patients had exercise-induced ventricular arrhythmias. Figure 1 shows the types of arrhythmias seen in these patients. One-hundred ninety-nine (52%) of the 383 patients had no ST depression on the exercise electrocardiogram, 85 (23%) had no defects on the initial thallium-201 images and 169 (44%) had no redistribution on the delayed thallium-201 images. Eighty-nine patients (23%) had no significant coronary artery disease when 250% luminal diameter narrowing was used as the criterion while 141 (37%) had no significant coronary artery disease when 270% stenosis was used as the criterion. Only 7 of the
No
V
Rare
arrhythmias
(5)
114) PVCs
(84)
PVCs (44)
(11) (2)
JULY 15, 1990
173
TABLE I Univariate Comparison of Clinical, Exercise and Electrocardiographic Variables in Patients With and Without Exercise-Induced Ventricular Arrhythmias EIVA
Variables
No EIVA
p Value
59i 10 91 65 49 59 12 1.8kO.8
57flO 82 64 43 67 10 1.7f0.8
0.006 0.02 0.91 0.61 0.09 0.50 0.38
55 1.1 f 1.2 2.4 f 2.7 2.0f 2.5 21
43 0.8f 1.03 1.8f2.0 1.3 f 2.0 15
0.02 0.008 0.04 0.004 0.14
Clinical Age (Y rs) % men % with typical angina % with previous Ml % on p blockers % on digitalis NYHA class Exercise variables % with ST dep Maximal ST dep (mm) No. leads with ST dep Duration of ST dep (min) % with horizontal or downsloping ST dep HR at peak exercise A HR rest - exercrse SBP at peak exercise A SBP rest -exercise Workload (METS) Duration of exercise (min) % with chest pain durtng exercise
128f26 53f21 158f26 28f22 5.9 f 2.6 6.0 f 2.7 19
127 f 26 54f23 154f27 28f24 6.4 f 2.8 6.3 f 2.8 21
Discrimination exercise-induced variate analysis:
0.56 0.74 0.17 0.88 0.10 0.29 0.73
dep = depression; EIVA = exercise-Induced ventrwlar arrhythmtas. HR = heart rate; AHR = change I” heart rate; MI = myocardlal Infarcton; NYHA = New York Heart Assoclatlon, SBP = systolic blood pressure; ASBP = change I” systolic blood pressure.
162 patients (4%) with exercise-induced ventricular arrhythmias did not have some abnormality on either the exercise electrocardiogram, thallium-201 images or the coronary angiogram compared to 33 of the 221 patients (15%) without these arrhythmias (p
