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Prevalence and Prognostic Significance of Exercise-Induced Right Bundle Branch Block
Prevalence and Prognostic Significance of Exercise-Induced Right Bundle Branch Block Ricardo Stein, MDa,b, Patricia Nguyen, MDb,*, Joshua Abella, MDb, Harold Olson, MDc, Jonathan Myers, PhDb, and Victor Froelicher, MDb Exercise-induced (EI) right bundle branch block (RBBB) is an infrequent electrocardiographic phenomenon, and controversy exists regarding its association with cardiovascular disease. We compared the prevalence and prognostic significance of RBBB, abnormal ST depression, and normal electrocardiographic findings in response to exercise testing in 9,623 consecutive veterans who underwent exercise testing from 1987 to 2007. EI RBBB, EI ST depression, and a normal exercise electrocardiographic response occurred in 0.24%, 15.2%, and 71.9% veterans, respectively. After appropriate exclusions, of the 8,047 patients analyzed, 6 patients in the EI RBBB subgroup died. Of these 6 deaths, 3 were cardiovascular deaths during the 9 years of follow-up. The annual death rate was 7.3% (1.4% cardiac deaths), 2.6% (1.2% cardiac deaths), and 1.8% (0.6% cardiac death) among those with EI RBBB, EI ST depression, and a normal ST response, respectively (p <0.0001). The patients with EI RBBB were significantly older, more overweight, and had a greater prevalence of coronary artery disease, heart failure, and hypertension compared to the 2 other subgroups. Patients with EI RBBB had an age-adjusted Cox proportional hazard ratio of 1.13 (p ⴝ 0.75, 95% confidence interval 0.51 to 2.5) for all-cause mortality and 1.57 (p ⴝ 0.43, 95% confidence interval 0.51 to 4.8) for cardiovascular mortality, respectively. In conclusion, EI RBBB is a rare occurrence during routine clinical exercise testing that appears to be benign. Published by Elsevier Inc. (Am J Cardiol 2010;105:677– 680)
Exercise-induced (EI) right bundle branch block (RBBB) is an infrequent electrocardiographic phenomenon, and controversy exists regarding its association with coronary artery disease (CAD) and heart failure.1–3 Although information about EI left BBB (LBBB) is available,1– 6 fewer studies of EI RBBB have been published.5,6 Therefore, in a large series of EI RBBB, we prospectively evaluated its prognostic significance compared to EI ST depression and a normal electrocardiographic response to exercise testing. Methods Consecutive adult patients who underwent clinically indicated exercise treadmill testing from 1987 to 2007 at the Long Beach and Palo Alto Veteran Affairs Medical Centers were evaluated (n ⫽ 9,623). Standard criteria were used to define RBBB, including the presence of (1) sinus rhythm; (2) QRS duration of ⱖ120 ms; (3) terminal R wave in lead V1 (eg, R, rR=, rsR=, rSR=, or qR); (4) slurred S wave in leads I and V6; and (5) T waves opposite in direction to the major QRS amplitude. a
Exercise Pathophysiology Research Laboratory, Cardiology Division, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil; bVeteran Affairs Palo Alto Health Care System and Stanford University School of Medicine, Palo Alto, California; and cVeteran Affairs Long Beach Health Care System, San Diego, California. Manuscript received August 10, 2009; revised manuscript received and accepted October 25, 2009. This study was supported by a grant from CNPq (Brasília, Brazil). *Corresponding author: Tel: (650) 815-8151; fax: (650) 852-3473. E-mail address: [email protected] (P. Nguyen). 0002-9149/10/$ – see front matter Published by Elsevier Inc. doi:10.1016/j.amjcard.2009.10.050
Only the first test performed was considered. A total of 338 women (3.5%) were excluded. We also excluded patients with the following electrocardiographic patterns that interfered with the analysis of the exercise electrocardiogram: (1) resting ST depression and/or left ventricular hypertrophy, paced rhythm, and pre-excitation syndromes (n ⫽ 675, 7%); (2) atrial fibrillation (n ⫽ 109, 1.1%); (3) RBBB at rest (n ⫽ 348, 3.6%); (4) LBBB at rest (n ⫽ 68, 0.7%); and (4) EI LBBB (n ⫽ 38, 0.39%). The final cohort for analysis consisted of 8,047 male veterans. The institutional review board approved the research protocol. All patients provided informed consent. The subjects underwent symptom-limited treadmill testing using an individualized ramp treadmill protocol and exercised to maximum exertion.7 Twelve-lead electrocardiographic data were recorded during exercise and for 5 minutes during recovery. Visual ST-segment depression and ST slopes were measured and read by 2 board-certified cardiologists. ST-segment depression was measured at the J junction, and the ST slope was measured during the following 60 ms of the ST segment. The exercise response was considered abnormal if the patient had ⱖ1 mm of horizontal or downsloping ST-segment depression in leads V5 or V6 measured at the J point using the PQ segment as the baseline, even in patients with early repolarization. Standard criteria for stopping were used, including serious arrhythmias, a decrease in systolic blood pressure to less than that at rest, ⬎3 mm ST-segment depression or elevation, severe angina pectoris, or central nervous system complaints. When the end point had been reached, the treadmill was stopped abruptly, and the patient was placed in the supine www.AJConline.org
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Table 1 Demographic, clinical, baseline electrocardiographic, and exercise test data and outcomes Variable Age (years) Height (inches) Weight (pounds) Body mass index (kg/m2) Women Coronary artery disease* Ischemic heart failure Nonischemic heart failure Hypertension Smoker Diabetes mellitus Obesity† Pulmonary disease At rest left bundle branch block At rest right bundle branch block Atrial fibrillation Left ventricle hypertrophy (strain) or paced rhythm At rest ST depression or pre-excitation Any diagnostic electrocardiographic Q wave At rest heart rate (beats/min) Maximum heart rate (beats/min) Peak systolic blood pressure (mm Hg) Metabolic equivalent Borg scale Exercise-induced ST-segment depression Exercise-induced left bundle branch block Exercise-induced right bundle branch block Annual all-cause mortality Annual cardiovascular mortality Survivors Deaths
Table 2 Male study cohort (after exclusions) Variable
Total Population (n ⫽ 9,623) 58.8 ⫾ 11.3 69.2 ⫾ 3.5 193.3 ⫾ 38.8 28.4 ⫾ 5.3 338 (3.5%) 22.3% 3.7% 3.4% 50.6% 58.2% 13.5% 32.1% 6.0% 0.7% 3.6% 1.1% 1.3% 5.7% 15.9% 77 ⫾ 21 138 ⫾ 24 177 ⫾ 29 8⫾3 17 ⫾ 3 8.0% 0.4% 0.24% 1.8% 0.6% 7,929 (82.4%) 1,694 (17.6%)
Data presented as mean ⫾ SD, numbers (%), or percentages. * Defined as presence of ⱖ50% coronary obstruction in any major epicardial artery as evaluated on coronary angiograms or evidence of myocardial ischemia on stress echocardiogram or nuclear stress test imaging. † Defined as body mass index ⬎30 kg/m2.
position within 1 minute. The baseline and maximum exercise variables, EI hypotension or angina, and exercise capacity, estimated in metabolic equivalents from the final treadmill speed and grade were recorded. The outcomes and demographics were compared among the patients with EI BBB, those with ⱖ1.0 mm horizontal or downsloping ST-segment depression (EI ST depression), and those with normal electrocardiographic responses. None of the patients with EI RBBB exhibited concomitant ST depression. The primary outcome variables were allcause and cardiovascular mortality. The California Death Index (from the California Department of Health Services) and the Social Security Death Index were used to ascertain the vital status of each patient as of December 31, 2007. The California Death Index provided the cause of death, which was confirmed by reviewing the Veteran Affairs Clinical Database. The differences among the subjects with EI RBBB, EI ST segment depression, and normal ST responses to exercise testing were compared. Analysis of variance with Bon-
Age (years) Height (inches) Weight (pounds) Body mass index (kg/m2) Coronary artery disease Ischemic heart failure Nonischemic heart failure Hypertension Smoker Diabetes mellitus Obesity Pulmonary disease Any diagnostic Q wave Heart rate at rest (beats/min) Maximum heart rate (beats/min) Peak systolic blood pressure (mm Hg) Metabolic equivalents Borg scale Annual all-cause mortality Annual cardiovascular mortality Survivors Deaths
Normal Electrocardiographic Exercise Response (n ⫽ 6,569)
EI ST Depression (n ⫽ 1,458)
EI RBBB (n ⫽ 23)
58 ⫾ 11 69 ⫾ 3 196 ⫾ 39 28.6 ⫾ 5
62 ⫾ 10 69 ⫾ 4 190 ⫾ 35 27.9 ⫾ 5
65 ⫾ 10* 69 ⫾ 3 201 ⫾ 56* 29.6 ⫾ 8*
19.3%
30.4%
39.1%*
2.1% 2.6%
3.4% 2.7%
4.3%* 8.7%*
49.4% 60.7% 13.45% 33.8% 6.6% 14.5
52.8% 54.6% 14.7% 27.2% 3.8% 18.9
52.2% 52.2%* 14.2% 34.8%† 4.3%‡ 8.7*
77 ⫾ 23
75 ⫾ 14
75 ⫾ 15‡
139 ⫾ 24
138 ⫾ 23
134 ⫾ 25
177 ⫾ 28
178 ⫾ 28
181 ⫾ 27
9⫾4 17 ⫾ 3 1.7%
8⫾3 17 ⫾ 3 2.4%
8⫾3 18 ⫾ 2 7.3%*
0.6%
1.2%
1.4%*
5,449 (82.9%) 1,120 (17.1%)
1,105 (75.8%) 17 (73.9%) 353 (24.2%) 6 (26.1%)
Data presented as mean ⫾ SD, percentages, or numbers (%). Analysis of variance indicated p ⬍0.05 as follows: * EI RBBB vs normal exercise electrocardiographic response and EI ST depression; † EI RBBB vs EI ST depression; ‡ EI RBBB vs normal exercise electrocardiographic response.
Figure 1. Kaplan-Meier survival curves for all-cause mortality.
ferroni post hoc adjustment for multiple comparisons and chi-square tests were used for continuous and dichotomous variables, respectively. All continuous variables exhibited a
Arrhythmias and Conduction Disturbances/Prognosis and Exercise-Induced RBBB
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Table 3 Characteristics of patients with exercise-induced (EI) right bundle branch block (RBBB) classified by vital status at end of follow-up
Table 4 Comparison of studies regarding exercise-induced (RI) right bundle branch block (RBBB)
Variable
Investigator
Age (years) Height (inches) Weight (pounds) Body mass index (kg/m2) Any Q wave Heart rate at rest (beats/min) Peak systolic blood pressure (mm Hg) Maximum heart rate (beats/min) Metabolic equivalents Borg scale Coronary artery disease Ischemic heart failure Nonischemic heart failure Hypertension Smoker Diabetes mellitus Obesity
EI RBBB Survived (n ⫽ 17)
EI RBBB Died (n ⫽ 6)
63.9 ⫾ 10.4 69.6 ⫾ 2.5 207.2 ⫾ 58.4 29.9 ⫾ 7.9 11.8% 77 ⫾ 16 186 ⫾ 29 140 ⫾ 23 8⫾3 18 ⫾ 2 29.4% 5.9% 0% 47.1% 58.8% 29.4% 41.7%
68.9 ⫾ 8.4 68.7 ⫾ 2.0 187.7 ⫾ 16.3 28.5 ⫾ 9.5 0% 70 ⫾ 6 170 ⫾ 16 111 ⫾ 19 7⫾3 19 ⫾ 2 66.7% 33.3% 0% 66.7% 50% 0% 12.5%
Data presented as mean ⫾ SD or percentages.
normal distribution and are presented as the mean ⫾ SD. Categorical variables are expressed as the absolute and relative (percentage) frequencies. p Values ⬍0.05 were considered statistically significant. All-cause and cardiovascular mortality were used as the primary end points for the Kaplan-Meier survival analysis. Cox proportional hazards analysis was used to determine which variables were independently and significantly associated with the time to death in multivariate models. The analyses were adjusted for age in years as a continuous variable. The Number Cruncher Statistical System (NCSS, Kaysville, Utah) was used for all statistical analyses. Results The demographic, clinical, baseline electrocardiographic, and exercise test data, and outcomes of the population of veterans screened (n ⫽ 9,623) and those meeting the inclusion and exclusion criteria (n ⫽ 8,047 male subjects) are listed in Tables 1 and 2, respectively. Most patients had a normal exercise electrocardiographic response. The patients with EI RBBB were significantly older, more overweight, and had a greater prevalence of CAD, heart failure, and hypertension than those with EI ST depression and a normal exercise electrocardiographic response (Table 2). The annual death rates for all-cause and cardiovascular mortality were greatest for the patients with EI RBBB and were lower for those with EI ST depression and those with normal exercise test results. Figure 1 shows the Kaplan-Meier plots. During an average follow-up of 8.8 ⫾ 5.4 years, 6 patients in the EI RBBB subgroup died (all-cause), of which 3 were cardiovascular in origin. Table 3 lists the characteristics of those with RBBB who survived and those who died. Patients with EI RBBB had an age-adjusted Cox proportional hazard ratio of 1.13 (95% confidence interval 0.51 to
Present study Moran et al3 Williams et al6 Wayne et al13 Bounhoure et al5 Boran et al11
Patients (n)
Age (years)
EI RBBB
8,047 5,990 10,176 4,100 16,500 2,200
65 63 61 59 60 51
23 (0.29%) 8 (0.13%) 13 (0.13%) 5 (0.12%) 7 (0.04%) 3 (0.14%)
2.5, p ⫽ 0.75) for all-cause mortality and 1.57 (95% confidence interval 0.51 to 4.8, p ⫽ 0.4) for cardiovascular mortality. Discussion In the present large, prospective cohort of male veterans who underwent routine clinical exercise treadmill testing, EI RBBB was an infrequent finding. Although EI RBBB was associated with an increased risk of all-cause and cardiovascular mortality, this greater risk was explained by older age and other clinical factors. BBBs are an uncommon finding in patients undergoing exercise testing. EI RBBB occurred in 0.29% of patients in our study, consistent with the findings from other published reports (Table 4). Similarly, and as reported in other published studies, EI LBBB occurs in approximately 0.5% of all patients undergoing exercise testing4 (0.39% in our cohort). The clinical implications of EI BBB remain controversial. Few studies have addressed this issue, but some investigators have attributed them to functional alterations of the conduction system mediated by autonomic influences.8 –10 Others have proposed a close relation with CAD.5,6,11 Bounhoure et al5 evaluated 16,500 exercise treadmill test results and found 7 patients (0.04%) with EI RBBB and 25 (0.15%) with EI LBBB, with all patients with EI RBBB having CAD. Williams et al,6 in a series of 10,176 exercise treadmill tests, found 37 patients (0.36%) with EI LBBB and 13 (0.13%) with EI RBBB. Again, CAD was very prevalent, with 70% of those with EI LBBB and all subjects with EI RBBB also having CAD. Boran et al11 identified 10 patients with EI BBB from 2,200 exercise treadmill test results (0.03% EI LBBB and 0.01% EI RBBB); all 10 also had CAD. However, only EI LBBB has been associated with increased major adverse cardiac events. A Cleveland Clinic case-control study, with provided 4-year follow-up data for 70 patients with EI LBBB and 70 matched controls, showed that EI LBBB was associated with a greater risk of death and major cardiac events.4 Similarly, increased morbidity and mortality have been shown with isolated EI ST-segment depression, a common manifestation of myocardial ischemia.12 To our knowledge, the present study is the first to demonstrate that EI RBBB appears to be benign and to compare its prognostic significance with EI ST depression and normal exercise responses (Figure 1). The present study had some limitations that should be addressed. Women were excluded from the military draft
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and rarely enlisted in the military in the past; thus, few women have undergone exercise testing in Veterans Affairs hospitals (3.5% in our laboratories). Our results might not be applicable to the general population undergoing exercise testing, because our sample was composed exclusively of male veterans and the data collection was performed at 2 Veterans Affairs facilities. Because the average age of our subjects was 65 years, we were unable to determine whether the prognostic behavior of EI RBBB would be similar in a younger population. However, because age seemed to explain most of the risk, it appears that EI RBBB is likely benign when found in younger subjects. The heart rate dependence phenomenon deserves some consideration; unfortunately, these data were not collected in our study. The little information regarding this issue suggests that when EI LBBB occurs at ⬍140 beats/min, the possibility of obstructive CAD increases.4,5 Clinical relevance has arisen from the information provided by the present study. Although EI RBBB is an uncommon finding during exercise treadmill testing, this diagnostic tool is performed millions of times every week worldwide. Our data support the conclusion that EI RBBB is mainly associated with aging and does not pose added risk. 1. Schneider JF, Thomas HE, Kreger BE, McNamara PM, Sorlie P, Kannell WB. Newly acquired left bundle branch block: the Framingham Study. Ann Intern Med 1980;92:37– 44.
2. Vasey C, O’Donnell J, Morris S, McHenry P. Exercise-induced left bundle branch block and its relation to coronary artery disease. Am J Cardiol 1985;56:892– 895. 3. Moran JF, Scurlock B, Henkin R, Scanlon PJ. The clinical significance of exercise- induced bundle branch block. J Electrocardiol 1992;25: 229 –235. 4. Grady TA, Chiu AC, Snader CE, Marwick TH, Thomas JD, Pashkow FJ, Lauer MS. Prognostic significance of exercise-induced left bundlebranch block. JAMA 1998;279:153–156. 5. Bounhoure JP, Donzeau JP, Doazan JP, Queyreau M, Galinier M, Estrabaud M, Les Puel J. Blocs de branche complets et cours des épreuves d’effort. Arch Mal Cœur 1991;84:167–171. 6. Williams MA, Esterbrooks DJ, Nair CK, Sailors MM, Sketch MH. Clinical significance of exercise-induced bundle branch block. Am J Cardiol 1988;61:346 –348. 7. Myers J, Buchanan N, Walsh D, Kramer M, McAuley P, HamiltonWessler M, Froelicher V. Comparison of the ramp versus standard exercise protocols. J Am Coll Cardiol 1991;17:1334 –1342. 8. Neuss H, Thormann J, Schlepper M. Electrophysiological findings in frequency-dependent left bundle branch block. Br Heart J 1974;36: 888 – 893. 9. Kafka H, Burgraf G. Exercise-induced left bundle branch block without myocardial ischemia. Am J Cardiol 1984;54:676 – 677. 10. Virtanen K, Heikkila J, Kala R, Siltanen P. Chest pain and rate dependent left bundle branch block in patients with normal coronary arteriograms. Chest 1982;81:325–331. 11. Boran KJ, Oliveros RA, Boulher CA, Beckmann CH, Seaworth JF. Ischemia-associated intraventricular conduction disturbances during exercise testing as a predictor of proximal left anterior descending coronary artery disease. Am J Cardiol 1983;51:1098 –1101. 12. Chang JA, Froelicher VF. Clinical and exercise test markers of prognosis in patients with stable coronary artery disease. Curr Probl Cardiol 1994;19:533–537. 13. Wayne VS, Bishop RL, Cook L, Spodick DH. Exercise-induced bundle branch block. Am J Cardiol 1983;52:283–287.
Exercise-induced (EI) right bundle branch block (RBBB) is an infrequent electrocardiographic phenomenon, and controversy exists regarding its association with coronary artery disease (CAD) and heart failure.1–3 Although information about EI left BBB (LBBB) is available,1– 6 fewer studies of EI RBBB have been published.5,6 Therefore, in a large series of EI RBBB, we prospectively evaluated its prognostic significance compared to EI ST depression and a normal electrocardiographic response to exercise testing. Methods Consecutive adult patients who underwent clinically indicated exercise treadmill testing from 1987 to 2007 at the Long Beach and Palo Alto Veteran Affairs Medical Centers were evaluated (n ⫽ 9,623). Standard criteria were used to define RBBB, including the presence of (1) sinus rhythm; (2) QRS duration of ⱖ120 ms; (3) terminal R wave in lead V1 (eg, R, rR=, rsR=, rSR=, or qR); (4) slurred S wave in leads I and V6; and (5) T waves opposite in direction to the major QRS amplitude. a
Exercise Pathophysiology Research Laboratory, Cardiology Division, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil; bVeteran Affairs Palo Alto Health Care System and Stanford University School of Medicine, Palo Alto, California; and cVeteran Affairs Long Beach Health Care System, San Diego, California. Manuscript received August 10, 2009; revised manuscript received and accepted October 25, 2009. This study was supported by a grant from CNPq (Brasília, Brazil). *Corresponding author: Tel: (650) 815-8151; fax: (650) 852-3473. E-mail address: [email protected] (P. Nguyen). 0002-9149/10/$ – see front matter Published by Elsevier Inc. doi:10.1016/j.amjcard.2009.10.050
Only the first test performed was considered. A total of 338 women (3.5%) were excluded. We also excluded patients with the following electrocardiographic patterns that interfered with the analysis of the exercise electrocardiogram: (1) resting ST depression and/or left ventricular hypertrophy, paced rhythm, and pre-excitation syndromes (n ⫽ 675, 7%); (2) atrial fibrillation (n ⫽ 109, 1.1%); (3) RBBB at rest (n ⫽ 348, 3.6%); (4) LBBB at rest (n ⫽ 68, 0.7%); and (4) EI LBBB (n ⫽ 38, 0.39%). The final cohort for analysis consisted of 8,047 male veterans. The institutional review board approved the research protocol. All patients provided informed consent. The subjects underwent symptom-limited treadmill testing using an individualized ramp treadmill protocol and exercised to maximum exertion.7 Twelve-lead electrocardiographic data were recorded during exercise and for 5 minutes during recovery. Visual ST-segment depression and ST slopes were measured and read by 2 board-certified cardiologists. ST-segment depression was measured at the J junction, and the ST slope was measured during the following 60 ms of the ST segment. The exercise response was considered abnormal if the patient had ⱖ1 mm of horizontal or downsloping ST-segment depression in leads V5 or V6 measured at the J point using the PQ segment as the baseline, even in patients with early repolarization. Standard criteria for stopping were used, including serious arrhythmias, a decrease in systolic blood pressure to less than that at rest, ⬎3 mm ST-segment depression or elevation, severe angina pectoris, or central nervous system complaints. When the end point had been reached, the treadmill was stopped abruptly, and the patient was placed in the supine www.AJConline.org
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The American Journal of Cardiology (www.AJConline.org)
Table 1 Demographic, clinical, baseline electrocardiographic, and exercise test data and outcomes Variable Age (years) Height (inches) Weight (pounds) Body mass index (kg/m2) Women Coronary artery disease* Ischemic heart failure Nonischemic heart failure Hypertension Smoker Diabetes mellitus Obesity† Pulmonary disease At rest left bundle branch block At rest right bundle branch block Atrial fibrillation Left ventricle hypertrophy (strain) or paced rhythm At rest ST depression or pre-excitation Any diagnostic electrocardiographic Q wave At rest heart rate (beats/min) Maximum heart rate (beats/min) Peak systolic blood pressure (mm Hg) Metabolic equivalent Borg scale Exercise-induced ST-segment depression Exercise-induced left bundle branch block Exercise-induced right bundle branch block Annual all-cause mortality Annual cardiovascular mortality Survivors Deaths
Table 2 Male study cohort (after exclusions) Variable
Total Population (n ⫽ 9,623) 58.8 ⫾ 11.3 69.2 ⫾ 3.5 193.3 ⫾ 38.8 28.4 ⫾ 5.3 338 (3.5%) 22.3% 3.7% 3.4% 50.6% 58.2% 13.5% 32.1% 6.0% 0.7% 3.6% 1.1% 1.3% 5.7% 15.9% 77 ⫾ 21 138 ⫾ 24 177 ⫾ 29 8⫾3 17 ⫾ 3 8.0% 0.4% 0.24% 1.8% 0.6% 7,929 (82.4%) 1,694 (17.6%)
Data presented as mean ⫾ SD, numbers (%), or percentages. * Defined as presence of ⱖ50% coronary obstruction in any major epicardial artery as evaluated on coronary angiograms or evidence of myocardial ischemia on stress echocardiogram or nuclear stress test imaging. † Defined as body mass index ⬎30 kg/m2.
position within 1 minute. The baseline and maximum exercise variables, EI hypotension or angina, and exercise capacity, estimated in metabolic equivalents from the final treadmill speed and grade were recorded. The outcomes and demographics were compared among the patients with EI BBB, those with ⱖ1.0 mm horizontal or downsloping ST-segment depression (EI ST depression), and those with normal electrocardiographic responses. None of the patients with EI RBBB exhibited concomitant ST depression. The primary outcome variables were allcause and cardiovascular mortality. The California Death Index (from the California Department of Health Services) and the Social Security Death Index were used to ascertain the vital status of each patient as of December 31, 2007. The California Death Index provided the cause of death, which was confirmed by reviewing the Veteran Affairs Clinical Database. The differences among the subjects with EI RBBB, EI ST segment depression, and normal ST responses to exercise testing were compared. Analysis of variance with Bon-
Age (years) Height (inches) Weight (pounds) Body mass index (kg/m2) Coronary artery disease Ischemic heart failure Nonischemic heart failure Hypertension Smoker Diabetes mellitus Obesity Pulmonary disease Any diagnostic Q wave Heart rate at rest (beats/min) Maximum heart rate (beats/min) Peak systolic blood pressure (mm Hg) Metabolic equivalents Borg scale Annual all-cause mortality Annual cardiovascular mortality Survivors Deaths
Normal Electrocardiographic Exercise Response (n ⫽ 6,569)
EI ST Depression (n ⫽ 1,458)
EI RBBB (n ⫽ 23)
58 ⫾ 11 69 ⫾ 3 196 ⫾ 39 28.6 ⫾ 5
62 ⫾ 10 69 ⫾ 4 190 ⫾ 35 27.9 ⫾ 5
65 ⫾ 10* 69 ⫾ 3 201 ⫾ 56* 29.6 ⫾ 8*
19.3%
30.4%
39.1%*
2.1% 2.6%
3.4% 2.7%
4.3%* 8.7%*
49.4% 60.7% 13.45% 33.8% 6.6% 14.5
52.8% 54.6% 14.7% 27.2% 3.8% 18.9
52.2% 52.2%* 14.2% 34.8%† 4.3%‡ 8.7*
77 ⫾ 23
75 ⫾ 14
75 ⫾ 15‡
139 ⫾ 24
138 ⫾ 23
134 ⫾ 25
177 ⫾ 28
178 ⫾ 28
181 ⫾ 27
9⫾4 17 ⫾ 3 1.7%
8⫾3 17 ⫾ 3 2.4%
8⫾3 18 ⫾ 2 7.3%*
0.6%
1.2%
1.4%*
5,449 (82.9%) 1,120 (17.1%)
1,105 (75.8%) 17 (73.9%) 353 (24.2%) 6 (26.1%)
Data presented as mean ⫾ SD, percentages, or numbers (%). Analysis of variance indicated p ⬍0.05 as follows: * EI RBBB vs normal exercise electrocardiographic response and EI ST depression; † EI RBBB vs EI ST depression; ‡ EI RBBB vs normal exercise electrocardiographic response.
Figure 1. Kaplan-Meier survival curves for all-cause mortality.
ferroni post hoc adjustment for multiple comparisons and chi-square tests were used for continuous and dichotomous variables, respectively. All continuous variables exhibited a
Arrhythmias and Conduction Disturbances/Prognosis and Exercise-Induced RBBB
679
Table 3 Characteristics of patients with exercise-induced (EI) right bundle branch block (RBBB) classified by vital status at end of follow-up
Table 4 Comparison of studies regarding exercise-induced (RI) right bundle branch block (RBBB)
Variable
Investigator
Age (years) Height (inches) Weight (pounds) Body mass index (kg/m2) Any Q wave Heart rate at rest (beats/min) Peak systolic blood pressure (mm Hg) Maximum heart rate (beats/min) Metabolic equivalents Borg scale Coronary artery disease Ischemic heart failure Nonischemic heart failure Hypertension Smoker Diabetes mellitus Obesity
EI RBBB Survived (n ⫽ 17)
EI RBBB Died (n ⫽ 6)
63.9 ⫾ 10.4 69.6 ⫾ 2.5 207.2 ⫾ 58.4 29.9 ⫾ 7.9 11.8% 77 ⫾ 16 186 ⫾ 29 140 ⫾ 23 8⫾3 18 ⫾ 2 29.4% 5.9% 0% 47.1% 58.8% 29.4% 41.7%
68.9 ⫾ 8.4 68.7 ⫾ 2.0 187.7 ⫾ 16.3 28.5 ⫾ 9.5 0% 70 ⫾ 6 170 ⫾ 16 111 ⫾ 19 7⫾3 19 ⫾ 2 66.7% 33.3% 0% 66.7% 50% 0% 12.5%
Data presented as mean ⫾ SD or percentages.
normal distribution and are presented as the mean ⫾ SD. Categorical variables are expressed as the absolute and relative (percentage) frequencies. p Values ⬍0.05 were considered statistically significant. All-cause and cardiovascular mortality were used as the primary end points for the Kaplan-Meier survival analysis. Cox proportional hazards analysis was used to determine which variables were independently and significantly associated with the time to death in multivariate models. The analyses were adjusted for age in years as a continuous variable. The Number Cruncher Statistical System (NCSS, Kaysville, Utah) was used for all statistical analyses. Results The demographic, clinical, baseline electrocardiographic, and exercise test data, and outcomes of the population of veterans screened (n ⫽ 9,623) and those meeting the inclusion and exclusion criteria (n ⫽ 8,047 male subjects) are listed in Tables 1 and 2, respectively. Most patients had a normal exercise electrocardiographic response. The patients with EI RBBB were significantly older, more overweight, and had a greater prevalence of CAD, heart failure, and hypertension than those with EI ST depression and a normal exercise electrocardiographic response (Table 2). The annual death rates for all-cause and cardiovascular mortality were greatest for the patients with EI RBBB and were lower for those with EI ST depression and those with normal exercise test results. Figure 1 shows the Kaplan-Meier plots. During an average follow-up of 8.8 ⫾ 5.4 years, 6 patients in the EI RBBB subgroup died (all-cause), of which 3 were cardiovascular in origin. Table 3 lists the characteristics of those with RBBB who survived and those who died. Patients with EI RBBB had an age-adjusted Cox proportional hazard ratio of 1.13 (95% confidence interval 0.51 to
Present study Moran et al3 Williams et al6 Wayne et al13 Bounhoure et al5 Boran et al11
Patients (n)
Age (years)
EI RBBB
8,047 5,990 10,176 4,100 16,500 2,200
65 63 61 59 60 51
23 (0.29%) 8 (0.13%) 13 (0.13%) 5 (0.12%) 7 (0.04%) 3 (0.14%)
2.5, p ⫽ 0.75) for all-cause mortality and 1.57 (95% confidence interval 0.51 to 4.8, p ⫽ 0.4) for cardiovascular mortality. Discussion In the present large, prospective cohort of male veterans who underwent routine clinical exercise treadmill testing, EI RBBB was an infrequent finding. Although EI RBBB was associated with an increased risk of all-cause and cardiovascular mortality, this greater risk was explained by older age and other clinical factors. BBBs are an uncommon finding in patients undergoing exercise testing. EI RBBB occurred in 0.29% of patients in our study, consistent with the findings from other published reports (Table 4). Similarly, and as reported in other published studies, EI LBBB occurs in approximately 0.5% of all patients undergoing exercise testing4 (0.39% in our cohort). The clinical implications of EI BBB remain controversial. Few studies have addressed this issue, but some investigators have attributed them to functional alterations of the conduction system mediated by autonomic influences.8 –10 Others have proposed a close relation with CAD.5,6,11 Bounhoure et al5 evaluated 16,500 exercise treadmill test results and found 7 patients (0.04%) with EI RBBB and 25 (0.15%) with EI LBBB, with all patients with EI RBBB having CAD. Williams et al,6 in a series of 10,176 exercise treadmill tests, found 37 patients (0.36%) with EI LBBB and 13 (0.13%) with EI RBBB. Again, CAD was very prevalent, with 70% of those with EI LBBB and all subjects with EI RBBB also having CAD. Boran et al11 identified 10 patients with EI BBB from 2,200 exercise treadmill test results (0.03% EI LBBB and 0.01% EI RBBB); all 10 also had CAD. However, only EI LBBB has been associated with increased major adverse cardiac events. A Cleveland Clinic case-control study, with provided 4-year follow-up data for 70 patients with EI LBBB and 70 matched controls, showed that EI LBBB was associated with a greater risk of death and major cardiac events.4 Similarly, increased morbidity and mortality have been shown with isolated EI ST-segment depression, a common manifestation of myocardial ischemia.12 To our knowledge, the present study is the first to demonstrate that EI RBBB appears to be benign and to compare its prognostic significance with EI ST depression and normal exercise responses (Figure 1). The present study had some limitations that should be addressed. Women were excluded from the military draft
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and rarely enlisted in the military in the past; thus, few women have undergone exercise testing in Veterans Affairs hospitals (3.5% in our laboratories). Our results might not be applicable to the general population undergoing exercise testing, because our sample was composed exclusively of male veterans and the data collection was performed at 2 Veterans Affairs facilities. Because the average age of our subjects was 65 years, we were unable to determine whether the prognostic behavior of EI RBBB would be similar in a younger population. However, because age seemed to explain most of the risk, it appears that EI RBBB is likely benign when found in younger subjects. The heart rate dependence phenomenon deserves some consideration; unfortunately, these data were not collected in our study. The little information regarding this issue suggests that when EI LBBB occurs at ⬍140 beats/min, the possibility of obstructive CAD increases.4,5 Clinical relevance has arisen from the information provided by the present study. Although EI RBBB is an uncommon finding during exercise treadmill testing, this diagnostic tool is performed millions of times every week worldwide. Our data support the conclusion that EI RBBB is mainly associated with aging and does not pose added risk. 1. Schneider JF, Thomas HE, Kreger BE, McNamara PM, Sorlie P, Kannell WB. Newly acquired left bundle branch block: the Framingham Study. Ann Intern Med 1980;92:37– 44.
2. Vasey C, O’Donnell J, Morris S, McHenry P. Exercise-induced left bundle branch block and its relation to coronary artery disease. Am J Cardiol 1985;56:892– 895. 3. Moran JF, Scurlock B, Henkin R, Scanlon PJ. The clinical significance of exercise- induced bundle branch block. J Electrocardiol 1992;25: 229 –235. 4. Grady TA, Chiu AC, Snader CE, Marwick TH, Thomas JD, Pashkow FJ, Lauer MS. Prognostic significance of exercise-induced left bundlebranch block. JAMA 1998;279:153–156. 5. Bounhoure JP, Donzeau JP, Doazan JP, Queyreau M, Galinier M, Estrabaud M, Les Puel J. Blocs de branche complets et cours des épreuves d’effort. Arch Mal Cœur 1991;84:167–171. 6. Williams MA, Esterbrooks DJ, Nair CK, Sailors MM, Sketch MH. Clinical significance of exercise-induced bundle branch block. Am J Cardiol 1988;61:346 –348. 7. Myers J, Buchanan N, Walsh D, Kramer M, McAuley P, HamiltonWessler M, Froelicher V. Comparison of the ramp versus standard exercise protocols. J Am Coll Cardiol 1991;17:1334 –1342. 8. Neuss H, Thormann J, Schlepper M. Electrophysiological findings in frequency-dependent left bundle branch block. Br Heart J 1974;36: 888 – 893. 9. Kafka H, Burgraf G. Exercise-induced left bundle branch block without myocardial ischemia. Am J Cardiol 1984;54:676 – 677. 10. Virtanen K, Heikkila J, Kala R, Siltanen P. Chest pain and rate dependent left bundle branch block in patients with normal coronary arteriograms. Chest 1982;81:325–331. 11. Boran KJ, Oliveros RA, Boulher CA, Beckmann CH, Seaworth JF. Ischemia-associated intraventricular conduction disturbances during exercise testing as a predictor of proximal left anterior descending coronary artery disease. Am J Cardiol 1983;51:1098 –1101. 12. Chang JA, Froelicher VF. Clinical and exercise test markers of prognosis in patients with stable coronary artery disease. Curr Probl Cardiol 1994;19:533–537. 13. Wayne VS, Bishop RL, Cook L, Spodick DH. Exercise-induced bundle branch block. Am J Cardiol 1983;52:283–287.