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Right bundle-branch block in anterior acute myocardial infarction in the coronary intervention era: Acute angiographic findings and prognosis
International Journal of Cardiology 116 (2007) 57 – 61 www.elsevier.com/locate/ijcard
Right bundle-branch block in anterior acute myocardial infarction in the coronary intervention era: Acute angiographic findings and prognosis Satoshi Kurisu ⁎, Ichiro Inoue, Takuji Kawagoe, Masaharu Ishihara, Yuji Shimatani, Takaki Hata, Yasuharu Nakama, Yasufumi Kijima, Eisuke Kagawa Department of Cardiology, Hiroshima City Hospital, 7-33, Moto-machi, Naka-ku, Hiroshima, 730-8518 Japan Received 5 November 2005; received in revised form 11 February 2006; accepted 24 February 2006 Available online 3 July 2006
Abstract Background: Previous studies in the prethrombolytic or thrombolytic era have reported that right bundle-branch block (RBBB) is associated with poor clinical outcome in patients with acute myocardial infarction (AMI). Methods and Results: The purpose of this study was to examine the relations between RBBB and angiographic findings or clinical outcomes in patients with AMI in the coronary intervention era. A total of 430 patients with a first anterior AMI who underwent coronary angiography within 12 h after the onset were enrolled in this study. Seventy-one patients (17%) had RBBB documented during their hospital stay. RBBB was documented on admission in 35 patients. Patients with RBBB were older (p < 0.01) and had prodromal angina less frequently (p = 0.03) than those without. On the initial angiograms, patients with RBBB had an occluded left anterior descending artery (p < 0.01) and multivessel disease (p = 0.01) more frequently than those without. Thirty-day mortality rate was significantly higher in patients with RBBB than in those without (14.0% vs 1.9%, p < 0.01). Multiple logistic-regression analysis demonstrated that RBBB (odds ratio 5.89, p < 0.01) and multivessel disease (odds ratio 4.36, p = 0.01) were independent predictors of 30-day mortality. Conclusions: Our data suggested that RBBB was still associated with poor clinical outcome in patients with anterior AMI even in the coronary intervention era. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Right bundle-branch block; Myocardial infarction; Ventricular function
1. Introduction Previous studies in the prethrombolytic era have reported that right bundle-branch block (RBBB) occurs in 3–29% of patients with acute myocardial infarction (AMI) [1–8]. Because of the blood supply of the conduction system, patients with anterior AMI and RBBB usually have large infarct sizes that are often accompanied by heart failure, ventricular arrhythmia or mortality. Although the introduction of thrombolytic therapy has affected the occurrence and resolution of RBBB [7–9], reduced mortality rate and improved left ventricular function in
⁎ Corresponding author. Tel.: +81 82 221 2291; fax: +81 82 223 1447. E-mail address: [email protected] (S. Kurisu). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.02.010
patients with AMI [10–12], RBBB still identified a subset of patients with high mortality rate in the thrombolytic era [13–16]. Because of lack of angiography before thrombolytic therapy, it remained unclear whether RBBB was dependent on the perfusion status of the infarct-related artery. To assess this issue, we examined the relation between RBBB and acute angiographic findings in patients with anterior AMI. Recent randomized trials indicated that coronary intervention might be superior to thrombolytic therapy with regard to the early and late clinical outcomes [17,18]. Thus, it is probable that the introduction of coronary intervention may have changed implications of RBBB in patients with anterior AMI. To assess this issue, we also examined the relations between RBBB and 30-day mortality or left ventricular function.
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2. Materials and methods 2.1. Study population Between January 1990 and December 2003, 430 patients with a first anterior AMI underwent coronary angiography within 12 h after the onset of chest pain. Anterior AMI was diagnosed by (1) chest pain consistent with ongoing myocardial ischemia persisting ≥ 30 min; (2) increase in serum creatine kinase to twice the normal upper value; and (3) presence of a culprit lesion in the left anterior descending artery. Serum creatine kinase was measured every 3 h for > 24 h, and peak creatine kinase value was obtained. Prodromal angina was defined as one or more typical chest pain episodes persisting < 30 min either at rest or on effort within 24 h before the onset of AMI. The study protocol was approved by the committee on ethics of our hospital. 2.2. Electrocardiogram Twelve-lead electrocardiograms were recorded on admission, every 3 h for the first 24 h and then daily. RBBB was defined by using standard electrocardiographic criteria; a QRS duration ≥ 120 ms was required. RBBB was classified as persistent when the patient either died or was discharged with RBBB and transient when there was no RBBB at discharge. Persistent RBBB was classified as new if it appeared after admission or was present on admission but was not recorded on an electrocardiogram within the preceding year, old if it was present in any previous electrocardiogram and indeterminate if it was present on admission with no previous electrocardiogram available for review. 2.3. Cardiac catheterization Left ventriculography and coronary angiography were performed by the femoral or brachial approach after intravenous infusion of 5000 U of heparin. Left ventriculography was performed in the 30° right anterior oblique projection. Left ventricular ejection fraction was measured by two independent technicians using the area–length method. Coronary angiography was performed after intracoronary infusion of nitroglycerin. The perfusion status of the left anterior descending artery was determined in accordance with the Thrombolysis in Myocardial Infarction (TIMI) study classification. Initial TIMI flow grade was assessed before the initiation of reperfusion therapy and final TIMI flow grade from the final angiographic frame. Multivessel coronary disease was defined as ≥ 75% stenosis in one or more vessels remote from the infarctrelated artery. The extent of collateral circulation was assessed from the pretreatment angiogram and classified in accordance with the method described by Rentrop et al [19]; collateral circulation was considered to be present if
the grade was ≥ 2. Coronary intervention including balloon angioplasty or stent placement was performed with the goal of restoring anterograde flow and obtaining a < 50% residual stenosis. The modality of treatment was based on the physician's decision. All patients were treated with aspirin and after stent placement were treated with ticlopidine at least for 4 weeks. 2.4. Clinical and angiographic follow-up Reinfarction was defined by the recurrence of persistent ischemic chest pain followed by at least two-fold re-elevation of creatine kinase from the last measured value. Predischarge angiography was performed about 2 weeks later. Follow-up was achieved for all patients by review of a clinical record. 2.5. Statistical analysis Fisher's exact test or the chi-square test was used to examine the associations between RBBB and the categorical variables. The mean values for continuous variables were compared with use of Student's t-test. Multiple logisticregression analysis was used to identify independent predictors of RBBB or death during 30-day follow-up. Differences were considered significant if the p-value was < 0.05. All data are expressed as mean ± S.D. 3. Results 3.1. Incidence of RBBB This study group included 430 patients. Of 430 patients, 71 (17%) had RBBB documented during their hospital stay. RBBB was documented on admission in 35 patients. It was persistent in 23 patients, and transient in 48 patients. Of 23 persistent RBBBs, 11 were new, 6 were old and the remaining 6 were indeterminate. 3.2. Baseline characteristics Patients with RBBB were older (p < 0.01) and had prodromal angina less frequently (p = 0.03) than those without. There was no significant difference in hypertension, diabetes, time to angiography between the 2 groups (Table 1). Average time from the onset of AMI to angiography was 3.8 ± 2.6 h. On the initial angiograms, patients with RBBB had an occluded left anterior descending artery (p < 0.01) and multivessel disease (p = 0.01) more frequently than those without. Collateral circulation was assessed in 411 patients (96%). There was no significant difference in collateral circulation between the two groups. 3.3. Efficacy of reperfusion therapy Of 430 patients, 395 patients (92%) underwent coronary intervention, and 25 patients (6%) underwent intracoronary
S. Kurisu et al. / International Journal of Cardiology 116 (2007) 57–61 Table 1 Clinical and initial angiographic findings
Table 2 Multivariate analysis assessing predictors of RBBB
RBBB during hospitalization
Age (years) Male Hypertension Diabetes Prodromal angina Time to angiography (h) Culprit lesion location Pre-first septal branch Post-first septal branch Initial TIMI flow grade TIMI 0 TIMI 1 TIMI 2 TIMI 3 Initial TIMI flow grade ≥2 Collateral circulation Unknown Grade 0 Grade 1 Grade 2 Grade 3 Collateral circulation ≥ 2 Number of diseased vessels 1 vessel 2 vessels 3 vessels Multivessel disease Reperfusion therapy Intracoronary thrombolysis Balloon angioplasty Stent placement None Final TIMI flow grade TIMI 0 TIMI 1 TIMI 2 TIMI 3
59
P-value
Present (n = 71)
Absent (n = 359)
66 ± 11 59 (83%) 26 (37%) 20 (28%) 17 (24%) 3.9 ± 2.4
62 ± 12 290 (81%) 126 (35%) 68 (19%) 116 (59%) 3.8 ± 2.6
<0.01 0.64 (NS) 0.81 (NS) 0.08 (NS) 0.03 0.67 (NS)
47 (66%) 24 (34%)
223 (62%) 136 (38%)
0.52 (NS)
55 (78%) 8 (11%) 6 (8%) 2 (3%) 8 (11%)
230 (64%) 30 (8%) 52 (15%) 47 (13%) 99 (28%)
0.06 (NS)
5 (7%) 31 (44%) 17 (24%) 12 (17%) 6 (8%) 18 (25%)
14 (4%) 145 (40%) 68 (19%) 107 (30%) 25 (7%) 132 (37%)
0.35 (NS)
41 (58%) 27 (38%) 3 (4%) 30 (42%)
262 (73%) 80 (22%) 17 (5%) 97 (27%)
2 (3%) 26 (36%) 41 (58%) 2 (3%)
23 (6%) 130 (36%) 198 (55%) 8 (2%)
0.84 (NS)
2 (3%) 2 (3%) 6 (8%) 61 (86%)
5 (1%) 0 (0%) 21 (6%) 333 (93%)
0.13 (NS)
<0.01
0.07 (NS) 0.03
0.01
RBBB, right bundle-branch block; TIMI, thrombolysis in myocardial infarction.
thrombolysis. The remaining 10 patients (2%) underwent neither, because they had a patent left anterior descending artery. There was no significant difference in final TIMI 3 flow between the two groups.
Age ≥ 65 years Female gender Hypertension Diabetes Prodromal angina Time to angiography ≤6 h Spontaneous reperfusion Multivessel disease
Odds ratio (95% CI)
P-value
2.17 (1.23–3.84) 0.62 (0.30–1.30) 1.01 (0.25–4.01) 1.71 (0.93–3.15) 0.54 (0.30–0.99) 1.12 (0.51–2.46) 0.28 (0.120.64) 1.73 (0.993.04)
<0.01 0.21 (NS) 0.96 (NS) 0.09 (NS) 0.045 0.77 (NS) <0.01 0.06 (NS)
RBBB, right-bundle branch block; CI, confidence interval.
period, 17 (4.0%) of the 430 patients died: 6 from left ventricular free wall rupture, 6 from pump failure, 2 from arrhythmia, one from renal failure, one from reinfarction and one from failed angioplasty. 30-day mortality rate was significantly higher in patients with RBBB than in those without (14.0% vs. 1.9%, p < 0.01). In addition, when patients were subdivided further into persistent and transient RBBB, 30-day mortality rate was significantly higher in patients with persistent RBBB than in those with transient RBBB (34.8% vs. 4.2%, p < 0.01). Multiple logistic-regression analysis demonstrated that age (odds ratio 2.17, p < 0.01), prodromal angina (odds ratio 0.54, p = 0.046) and spontaneous anterograde flow (odds ratio 0.28, p < 0.01) were independent predictors of RBBB (Table 2). Multiple logistic-regression analysis demonstrated that RBBB (odds ratio 5.89, p < 0.01) and multivessel disease (odds ratio 4.36, p = 0.01) were independent predictors of 30-day mortality (Table 3). 3.5. Ventricular function Pretreatment left ventriculography was performed in 340 patients, and left ventricular ejection fraction was significantly lower in patients with RBBB than in those without (43 ± 13% vs 49 ± 10%, p < 0.01). Predischarge left ventriculography was performed in 336 patients at 16 ± 5 days, and left ventricular ejection fraction was significantly lower in patients with RBBB than in those without (45 ± 14% vs. 55 ± 14%, p < 0.01).
3.4. Clinical follow-up
Table 3 Multivariate analysis assessing predictors of death during 30-day follow-up
After admission, there was no significant difference in the medication such as calcium channel blockers (43% vs. 55%, p = 0.08), angiotensin-converting enzyme inhibitors (26% vs. 36%, p = 0.15) or β-blockers (11% vs. 9%, p = 0.45) between the two groups. Peak creatine kinase was higher in patients with RBBB than in those without (5723 ± 4572 vs. 3594 ± 2692 IU/liter, p < 0.01). Reinfarction occurred in 15 patients (3.5%). There was no significant difference in reinfarction between the two groups. During the 30-day follow-up
RBBB Age ≥65 years Female gender Hypertension Diabetes Prodromal angina Time to angiography ≤6 h Multivessel disease
Odds ratio (95% CI)
P-value
5.89 (2.01–17.34) 2.48 (0.70–8.73) 0.97 (0.29–3.28) 1.76 (0.60–5.16) 1.26 (0.39–4.06) 1.31 (0.44–3.95) 1.67 (0.33–8.35) 4.36 (1.42–13.40)
<0.01 0.16 (NS) 0.96 (NS) 0.30 (NS) 0.70 (NS) 0.63 (NS) 0.53 (NS) 0.01
RBBB, right-bundle branch block; CI, confidence interval.
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4. Discussion 4.1. Present findings The major findings of this study were (1) RBBB was associated with older age, less prodromal angina and less spontaneous anterograde flow; (2) RBBB was a strong predictor of 30-day mortality even in the percutaneous coronary intervention era; and (3) RBBB was associated with poor left ventricular function during early phase of anterior AMI. 4.2. RBBB in the thrombolytic era Previous studies have shown that RBBB still identifies a subset of patients with high mortality rate in the thrombolytic era [13–15]. Although thrombolytic therapy has been widely used to restore anterograde flow, the most aggressive thrombolytic regimen achieves TIMI flow grade 3 in only 50% of patients within 90 min of initiation of therapy [20]. Moreover, early reocclusion has been reported in 5–10% of patients [20] and late reocclusion in 30% of patients [21]. These limited effects might result in unfavorable outcome in patients with RBBB even after thrombolytic therapy. 4.3. RBBB in the coronary intervention era Recent studies have demonstrated that coronary intervention is more effective than thrombolytic therapy in reducing mortality, reinfarction and stroke with the greatest absolute benefit in patients who are at the highest risk [17,18]. Guerrero et al. [22] recently reported that patients with AMI and RBBB had higher mortality rate despite treatment with primary angioplasty. However, in their study, patients with RBBB had higher percentage of anterior AMI than those without. This bias might result in unfavorable outcome in patients with RBBB even after primary angioplasty. That was why our study included only patients with a first anterior AMI who underwent coronary angiography. It was noteworthy that 92% of the patients underwent coronary intervention, and 92% of the patients obtained TIMI 3 flow. Our study allows a better understanding of RBBB that might influence outcome in patients with anterior AMI. Our study demonstrated that RBBB was associated with age, prodromal angina and spontaneous anterograde flow. In fact, these factors have been known to be associated with infarct size or mortality in patients with AMI. Shiraki et al [23] recently reported that prodromal angina was associated with lower incidence of complete atrioventricular block in patients with inferior AMI. Our study also demonstrated that prodromal angina was associated with lower incidence of RBBB in patients with anterior AMI. According to their and our studies, prodromal angina may have provided some protection against the subsequent ischemic burden on not only the myocardium but also the conduction system. Our
study demonstrated that patients with RBBB had lower left ventricular ejection fraction and higher 30-day mortality rate than those without. We thought that these adverse outcomes could be explained by larger infarct size and more frequent multivessel disease in patients with RBBB. In fact, the rate of use of calcium channel blockers is high, and that of β-blockers is low particularly in Japan, where coronary artery spasm is more prevalent than in the West [24]. On the contrary, it is known that the salutary effect of βblockers is greatest in high-risk patients. Patients with anterior AMI and RBBB should be recognized early and receive prompt and aggressive treatment such as β-blockers [25] or intraaortic balloon pumping [26]. 4.4. Study limitations This study suffers from limitations common to all nonrandomized, retrospective analyses. First, this study did not include a matched control population who did not undergo reperfusion therapy. We could not assess the impact of coronary intervention on left ventricular function or prognosis in patients with AMI and RBBB. Second, because serial left ventriculograms were obtained incompletely, we could not perform subanalysis of new, old or indeterminate RBBB regarding left ventricular function. Finally, we could not assess the impact of RBBB on long-term prognosis in the coronary intervention era. 4.5. Conclusions Our data demonstrated that RBBB was still associated with poor left ventricular function and high 30-day mortality in patients with anterior AMI even in the coronary intervention era. Patients with anterior AMI and RBBB should be recognized early and receive prompt and aggressive treatment. References [1] Godman MJ, Lassers BW, Julian DG. Complete bundle-branch block complication in acute myocardial infarction. N Engl J Med 1970;282: 237–40. [2] Roos JC, Duning AJ. Right bundle-branch block and left axis deviation in acute myocardial infarction. Br Heart J 1970;32:847–51. [3] Col JJ, Weinberg SL. Incidence and mortality of intraventricular conduction defects in acute myocardial infarction. Am J Cardiol 1972;29:344–50. [4] Scheinman M, Brenman B. Clinical and anatomic implication of intraventricular conduction block in acute myocardial infarction. Circulation 1972;46:753–60. [5] Scheidt S, Killip T. Bundle-branch block complicating acute myocardial infarction. JAMA 1972;222:919–24. [6] Atkins JM, Leshin SJ, Blomqvist CG, Mullins CB. Ventricular conduction blocks and sudden death during acute myocardial infarction: potential indication for pacing. N Engl J Med 1973; 288:281–4. [7] Hindman MC, Wagner GS, JaRo M, et al. The clinical significance of bundle branch block complicating acute myocardial infarction: I. Clinical characteristics, hospital mortality, and 1-year follow-up. Circulation 1978;58:679–88.
S. Kurisu et al. / International Journal of Cardiology 116 (2007) 57–61 [8] Ricou F, Nicod P, Gilpin E, Henning H, Ross Jr J. Influence of right bundle branch block on short- and long-term survival after acute anterior myocardial infarction. J Am Coll Cardiol 1991;17:858–63. [9] Roth A, Miller HI, Glick A, Barbash GI, Laniado S. Rapid resolution of new right bundle branch block in acute myocardial infarction patients after thrombolytic therapy. PACE 1993;16:13–8. [10] Grines CL, DeMaria AN. Optimal utilization of thrombolytic therapy for acute myocardial infarction: concepts and controversies. J Am Coll Cardiol 1990;16:223–31. [11] Nicod P, Zimmerman M, Scherrer U. The challenge of further reducing cardiac mortality in the thrombolytic era. Circulation 1993;87:640–2. [12] Fibrinolytic Therapy Trialists (FTT) Collaborative Group. Indications for thrombolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomized trials of more than 1000 patients. Lancet 1994;343:311–22. [13] Newby KH, Pisano E, Krucoff MW, Green C, Natale A. Incidence and clinical relevance of the occurrence of bundle-branch block in patients treated with thrombolytic therapy. Circulation 1996;94:2424–8. [14] Melgarejo-Moreno A, Galcera-Tomas J, Garcia-Alberola A, et al. Incidence, clinical characteristics, and prognostic significance of right bundle-branch block in acute myocardial infarction: a study in the thrombolytic era. Circulation 1997;96:1139–44. [15] Sgarbossa EB, Pinski SL, Topol EJ, et al. Acute myocardial infarction and complete bundle branch block at hospital admission: clinical characteristics and outcome in the thrombolytic era. J Am Coll Cardiol 1998;31:105–10. [16] Abidov A, Kaluski E, Hod H, et al. Influence of conduction disturbances on clinical outcome in patients with acute myocardial infarction receiving thrombolysis (results from the ARGAMI-2 study). Am J Cardiol 2004;93:76–80. [17] Zijlstra F, Hoorntje JC, de Boer MJ, et al. Long-term benefit of primary angioplasty as compared with thrombolytic therapy for acute myocardial infarction. N Engl J Med 1999;341:1413–9. [18] Schomig A, Kastrati A, Dirschinger J, et al. Coronary stenting plus platelet glycoprotein IIb/IIIa blockade compared with tissue plasmin-
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ogen activator in acute myocardial infarction. N Engl J Med 2000;343:385–91. Rentrop KP, Cohen M, Blanke H, Phillips RA. Changes in collateral channel filling immediately after controlled coronary artery occlusion by an angioplasty balloon in human subjects. J Am Coll Cardiol 1985; 5:587–92. The GUSTO angiographic investigators. The effect of tissue plasminogen activator, streptokinase, or both on coronary artery patency, ventricular function, and survival after acute myocardial infarction. N Engl J Med 1993;329:1615–22. Meijer A, Verheugt FW, Werter CJ, Lie KI, van der Pol JM, van Eenige MJ. Aspirin versus coumadin in the prevention of reocclusion and recurrent ischemia after successful thrombolysis: a prospective placebo-controlled angiographic study: results of the APRICOT study. Circulation 1993;87:1524–30. Guerrero M, Harjai K, Stone GW, et al. Comparison of the prognostic effect of left versus right versus no bundle branch block on presenting electrocardiogram in acute myocardial infarction patients treated with primary angioplasty in the primary angioplasty in myocardial infarction trials. Am J Cardiol 2005;96:482–8. Shiraki H, Yoshikawa T, Anzai T, et al. Association between preinfarction angina and a lower risk of right ventricular infarction. N Engl J Med 1998;338:941–7. The Japanese β-blockers and calcium antagonists myocardial infarction (JBCMI) investigators. Comparison of the effects of beta blockers and calcium antagonists on cardiovascular events after acute myocardial infarction in Japanese subjects. Am J Cardiol 2004;93: 969–73. Kernis SJ, Harjai KJ, Stone GW, et al. Does beta-blocker therapy improve clinical outcomes of acute myocardial infarction after successful primary angioplasty? J Am Coll Cardiol 2004;43:1773–9. Kurisu S, Inoue I, Kawagoe T, et al. Effect of intraaortic balloon pumping on left ventricular function in patients with persistent ST segment elevation after revascularization for acute myocardial infarction. Circ J 2003;67:35–9.
Right bundle-branch block in anterior acute myocardial infarction in the coronary intervention era: Acute angiographic findings and prognosis Satoshi Kurisu ⁎, Ichiro Inoue, Takuji Kawagoe, Masaharu Ishihara, Yuji Shimatani, Takaki Hata, Yasuharu Nakama, Yasufumi Kijima, Eisuke Kagawa Department of Cardiology, Hiroshima City Hospital, 7-33, Moto-machi, Naka-ku, Hiroshima, 730-8518 Japan Received 5 November 2005; received in revised form 11 February 2006; accepted 24 February 2006 Available online 3 July 2006
Abstract Background: Previous studies in the prethrombolytic or thrombolytic era have reported that right bundle-branch block (RBBB) is associated with poor clinical outcome in patients with acute myocardial infarction (AMI). Methods and Results: The purpose of this study was to examine the relations between RBBB and angiographic findings or clinical outcomes in patients with AMI in the coronary intervention era. A total of 430 patients with a first anterior AMI who underwent coronary angiography within 12 h after the onset were enrolled in this study. Seventy-one patients (17%) had RBBB documented during their hospital stay. RBBB was documented on admission in 35 patients. Patients with RBBB were older (p < 0.01) and had prodromal angina less frequently (p = 0.03) than those without. On the initial angiograms, patients with RBBB had an occluded left anterior descending artery (p < 0.01) and multivessel disease (p = 0.01) more frequently than those without. Thirty-day mortality rate was significantly higher in patients with RBBB than in those without (14.0% vs 1.9%, p < 0.01). Multiple logistic-regression analysis demonstrated that RBBB (odds ratio 5.89, p < 0.01) and multivessel disease (odds ratio 4.36, p = 0.01) were independent predictors of 30-day mortality. Conclusions: Our data suggested that RBBB was still associated with poor clinical outcome in patients with anterior AMI even in the coronary intervention era. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Right bundle-branch block; Myocardial infarction; Ventricular function
1. Introduction Previous studies in the prethrombolytic era have reported that right bundle-branch block (RBBB) occurs in 3–29% of patients with acute myocardial infarction (AMI) [1–8]. Because of the blood supply of the conduction system, patients with anterior AMI and RBBB usually have large infarct sizes that are often accompanied by heart failure, ventricular arrhythmia or mortality. Although the introduction of thrombolytic therapy has affected the occurrence and resolution of RBBB [7–9], reduced mortality rate and improved left ventricular function in
⁎ Corresponding author. Tel.: +81 82 221 2291; fax: +81 82 223 1447. E-mail address: [email protected] (S. Kurisu). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.02.010
patients with AMI [10–12], RBBB still identified a subset of patients with high mortality rate in the thrombolytic era [13–16]. Because of lack of angiography before thrombolytic therapy, it remained unclear whether RBBB was dependent on the perfusion status of the infarct-related artery. To assess this issue, we examined the relation between RBBB and acute angiographic findings in patients with anterior AMI. Recent randomized trials indicated that coronary intervention might be superior to thrombolytic therapy with regard to the early and late clinical outcomes [17,18]. Thus, it is probable that the introduction of coronary intervention may have changed implications of RBBB in patients with anterior AMI. To assess this issue, we also examined the relations between RBBB and 30-day mortality or left ventricular function.
58
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2. Materials and methods 2.1. Study population Between January 1990 and December 2003, 430 patients with a first anterior AMI underwent coronary angiography within 12 h after the onset of chest pain. Anterior AMI was diagnosed by (1) chest pain consistent with ongoing myocardial ischemia persisting ≥ 30 min; (2) increase in serum creatine kinase to twice the normal upper value; and (3) presence of a culprit lesion in the left anterior descending artery. Serum creatine kinase was measured every 3 h for > 24 h, and peak creatine kinase value was obtained. Prodromal angina was defined as one or more typical chest pain episodes persisting < 30 min either at rest or on effort within 24 h before the onset of AMI. The study protocol was approved by the committee on ethics of our hospital. 2.2. Electrocardiogram Twelve-lead electrocardiograms were recorded on admission, every 3 h for the first 24 h and then daily. RBBB was defined by using standard electrocardiographic criteria; a QRS duration ≥ 120 ms was required. RBBB was classified as persistent when the patient either died or was discharged with RBBB and transient when there was no RBBB at discharge. Persistent RBBB was classified as new if it appeared after admission or was present on admission but was not recorded on an electrocardiogram within the preceding year, old if it was present in any previous electrocardiogram and indeterminate if it was present on admission with no previous electrocardiogram available for review. 2.3. Cardiac catheterization Left ventriculography and coronary angiography were performed by the femoral or brachial approach after intravenous infusion of 5000 U of heparin. Left ventriculography was performed in the 30° right anterior oblique projection. Left ventricular ejection fraction was measured by two independent technicians using the area–length method. Coronary angiography was performed after intracoronary infusion of nitroglycerin. The perfusion status of the left anterior descending artery was determined in accordance with the Thrombolysis in Myocardial Infarction (TIMI) study classification. Initial TIMI flow grade was assessed before the initiation of reperfusion therapy and final TIMI flow grade from the final angiographic frame. Multivessel coronary disease was defined as ≥ 75% stenosis in one or more vessels remote from the infarctrelated artery. The extent of collateral circulation was assessed from the pretreatment angiogram and classified in accordance with the method described by Rentrop et al [19]; collateral circulation was considered to be present if
the grade was ≥ 2. Coronary intervention including balloon angioplasty or stent placement was performed with the goal of restoring anterograde flow and obtaining a < 50% residual stenosis. The modality of treatment was based on the physician's decision. All patients were treated with aspirin and after stent placement were treated with ticlopidine at least for 4 weeks. 2.4. Clinical and angiographic follow-up Reinfarction was defined by the recurrence of persistent ischemic chest pain followed by at least two-fold re-elevation of creatine kinase from the last measured value. Predischarge angiography was performed about 2 weeks later. Follow-up was achieved for all patients by review of a clinical record. 2.5. Statistical analysis Fisher's exact test or the chi-square test was used to examine the associations between RBBB and the categorical variables. The mean values for continuous variables were compared with use of Student's t-test. Multiple logisticregression analysis was used to identify independent predictors of RBBB or death during 30-day follow-up. Differences were considered significant if the p-value was < 0.05. All data are expressed as mean ± S.D. 3. Results 3.1. Incidence of RBBB This study group included 430 patients. Of 430 patients, 71 (17%) had RBBB documented during their hospital stay. RBBB was documented on admission in 35 patients. It was persistent in 23 patients, and transient in 48 patients. Of 23 persistent RBBBs, 11 were new, 6 were old and the remaining 6 were indeterminate. 3.2. Baseline characteristics Patients with RBBB were older (p < 0.01) and had prodromal angina less frequently (p = 0.03) than those without. There was no significant difference in hypertension, diabetes, time to angiography between the 2 groups (Table 1). Average time from the onset of AMI to angiography was 3.8 ± 2.6 h. On the initial angiograms, patients with RBBB had an occluded left anterior descending artery (p < 0.01) and multivessel disease (p = 0.01) more frequently than those without. Collateral circulation was assessed in 411 patients (96%). There was no significant difference in collateral circulation between the two groups. 3.3. Efficacy of reperfusion therapy Of 430 patients, 395 patients (92%) underwent coronary intervention, and 25 patients (6%) underwent intracoronary
S. Kurisu et al. / International Journal of Cardiology 116 (2007) 57–61 Table 1 Clinical and initial angiographic findings
Table 2 Multivariate analysis assessing predictors of RBBB
RBBB during hospitalization
Age (years) Male Hypertension Diabetes Prodromal angina Time to angiography (h) Culprit lesion location Pre-first septal branch Post-first septal branch Initial TIMI flow grade TIMI 0 TIMI 1 TIMI 2 TIMI 3 Initial TIMI flow grade ≥2 Collateral circulation Unknown Grade 0 Grade 1 Grade 2 Grade 3 Collateral circulation ≥ 2 Number of diseased vessels 1 vessel 2 vessels 3 vessels Multivessel disease Reperfusion therapy Intracoronary thrombolysis Balloon angioplasty Stent placement None Final TIMI flow grade TIMI 0 TIMI 1 TIMI 2 TIMI 3
59
P-value
Present (n = 71)
Absent (n = 359)
66 ± 11 59 (83%) 26 (37%) 20 (28%) 17 (24%) 3.9 ± 2.4
62 ± 12 290 (81%) 126 (35%) 68 (19%) 116 (59%) 3.8 ± 2.6
<0.01 0.64 (NS) 0.81 (NS) 0.08 (NS) 0.03 0.67 (NS)
47 (66%) 24 (34%)
223 (62%) 136 (38%)
0.52 (NS)
55 (78%) 8 (11%) 6 (8%) 2 (3%) 8 (11%)
230 (64%) 30 (8%) 52 (15%) 47 (13%) 99 (28%)
0.06 (NS)
5 (7%) 31 (44%) 17 (24%) 12 (17%) 6 (8%) 18 (25%)
14 (4%) 145 (40%) 68 (19%) 107 (30%) 25 (7%) 132 (37%)
0.35 (NS)
41 (58%) 27 (38%) 3 (4%) 30 (42%)
262 (73%) 80 (22%) 17 (5%) 97 (27%)
2 (3%) 26 (36%) 41 (58%) 2 (3%)
23 (6%) 130 (36%) 198 (55%) 8 (2%)
0.84 (NS)
2 (3%) 2 (3%) 6 (8%) 61 (86%)
5 (1%) 0 (0%) 21 (6%) 333 (93%)
0.13 (NS)
<0.01
0.07 (NS) 0.03
0.01
RBBB, right bundle-branch block; TIMI, thrombolysis in myocardial infarction.
thrombolysis. The remaining 10 patients (2%) underwent neither, because they had a patent left anterior descending artery. There was no significant difference in final TIMI 3 flow between the two groups.
Age ≥ 65 years Female gender Hypertension Diabetes Prodromal angina Time to angiography ≤6 h Spontaneous reperfusion Multivessel disease
Odds ratio (95% CI)
P-value
2.17 (1.23–3.84) 0.62 (0.30–1.30) 1.01 (0.25–4.01) 1.71 (0.93–3.15) 0.54 (0.30–0.99) 1.12 (0.51–2.46) 0.28 (0.120.64) 1.73 (0.993.04)
<0.01 0.21 (NS) 0.96 (NS) 0.09 (NS) 0.045 0.77 (NS) <0.01 0.06 (NS)
RBBB, right-bundle branch block; CI, confidence interval.
period, 17 (4.0%) of the 430 patients died: 6 from left ventricular free wall rupture, 6 from pump failure, 2 from arrhythmia, one from renal failure, one from reinfarction and one from failed angioplasty. 30-day mortality rate was significantly higher in patients with RBBB than in those without (14.0% vs. 1.9%, p < 0.01). In addition, when patients were subdivided further into persistent and transient RBBB, 30-day mortality rate was significantly higher in patients with persistent RBBB than in those with transient RBBB (34.8% vs. 4.2%, p < 0.01). Multiple logistic-regression analysis demonstrated that age (odds ratio 2.17, p < 0.01), prodromal angina (odds ratio 0.54, p = 0.046) and spontaneous anterograde flow (odds ratio 0.28, p < 0.01) were independent predictors of RBBB (Table 2). Multiple logistic-regression analysis demonstrated that RBBB (odds ratio 5.89, p < 0.01) and multivessel disease (odds ratio 4.36, p = 0.01) were independent predictors of 30-day mortality (Table 3). 3.5. Ventricular function Pretreatment left ventriculography was performed in 340 patients, and left ventricular ejection fraction was significantly lower in patients with RBBB than in those without (43 ± 13% vs 49 ± 10%, p < 0.01). Predischarge left ventriculography was performed in 336 patients at 16 ± 5 days, and left ventricular ejection fraction was significantly lower in patients with RBBB than in those without (45 ± 14% vs. 55 ± 14%, p < 0.01).
3.4. Clinical follow-up
Table 3 Multivariate analysis assessing predictors of death during 30-day follow-up
After admission, there was no significant difference in the medication such as calcium channel blockers (43% vs. 55%, p = 0.08), angiotensin-converting enzyme inhibitors (26% vs. 36%, p = 0.15) or β-blockers (11% vs. 9%, p = 0.45) between the two groups. Peak creatine kinase was higher in patients with RBBB than in those without (5723 ± 4572 vs. 3594 ± 2692 IU/liter, p < 0.01). Reinfarction occurred in 15 patients (3.5%). There was no significant difference in reinfarction between the two groups. During the 30-day follow-up
RBBB Age ≥65 years Female gender Hypertension Diabetes Prodromal angina Time to angiography ≤6 h Multivessel disease
Odds ratio (95% CI)
P-value
5.89 (2.01–17.34) 2.48 (0.70–8.73) 0.97 (0.29–3.28) 1.76 (0.60–5.16) 1.26 (0.39–4.06) 1.31 (0.44–3.95) 1.67 (0.33–8.35) 4.36 (1.42–13.40)
<0.01 0.16 (NS) 0.96 (NS) 0.30 (NS) 0.70 (NS) 0.63 (NS) 0.53 (NS) 0.01
RBBB, right-bundle branch block; CI, confidence interval.
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4. Discussion 4.1. Present findings The major findings of this study were (1) RBBB was associated with older age, less prodromal angina and less spontaneous anterograde flow; (2) RBBB was a strong predictor of 30-day mortality even in the percutaneous coronary intervention era; and (3) RBBB was associated with poor left ventricular function during early phase of anterior AMI. 4.2. RBBB in the thrombolytic era Previous studies have shown that RBBB still identifies a subset of patients with high mortality rate in the thrombolytic era [13–15]. Although thrombolytic therapy has been widely used to restore anterograde flow, the most aggressive thrombolytic regimen achieves TIMI flow grade 3 in only 50% of patients within 90 min of initiation of therapy [20]. Moreover, early reocclusion has been reported in 5–10% of patients [20] and late reocclusion in 30% of patients [21]. These limited effects might result in unfavorable outcome in patients with RBBB even after thrombolytic therapy. 4.3. RBBB in the coronary intervention era Recent studies have demonstrated that coronary intervention is more effective than thrombolytic therapy in reducing mortality, reinfarction and stroke with the greatest absolute benefit in patients who are at the highest risk [17,18]. Guerrero et al. [22] recently reported that patients with AMI and RBBB had higher mortality rate despite treatment with primary angioplasty. However, in their study, patients with RBBB had higher percentage of anterior AMI than those without. This bias might result in unfavorable outcome in patients with RBBB even after primary angioplasty. That was why our study included only patients with a first anterior AMI who underwent coronary angiography. It was noteworthy that 92% of the patients underwent coronary intervention, and 92% of the patients obtained TIMI 3 flow. Our study allows a better understanding of RBBB that might influence outcome in patients with anterior AMI. Our study demonstrated that RBBB was associated with age, prodromal angina and spontaneous anterograde flow. In fact, these factors have been known to be associated with infarct size or mortality in patients with AMI. Shiraki et al [23] recently reported that prodromal angina was associated with lower incidence of complete atrioventricular block in patients with inferior AMI. Our study also demonstrated that prodromal angina was associated with lower incidence of RBBB in patients with anterior AMI. According to their and our studies, prodromal angina may have provided some protection against the subsequent ischemic burden on not only the myocardium but also the conduction system. Our
study demonstrated that patients with RBBB had lower left ventricular ejection fraction and higher 30-day mortality rate than those without. We thought that these adverse outcomes could be explained by larger infarct size and more frequent multivessel disease in patients with RBBB. In fact, the rate of use of calcium channel blockers is high, and that of β-blockers is low particularly in Japan, where coronary artery spasm is more prevalent than in the West [24]. On the contrary, it is known that the salutary effect of βblockers is greatest in high-risk patients. Patients with anterior AMI and RBBB should be recognized early and receive prompt and aggressive treatment such as β-blockers [25] or intraaortic balloon pumping [26]. 4.4. Study limitations This study suffers from limitations common to all nonrandomized, retrospective analyses. First, this study did not include a matched control population who did not undergo reperfusion therapy. We could not assess the impact of coronary intervention on left ventricular function or prognosis in patients with AMI and RBBB. Second, because serial left ventriculograms were obtained incompletely, we could not perform subanalysis of new, old or indeterminate RBBB regarding left ventricular function. Finally, we could not assess the impact of RBBB on long-term prognosis in the coronary intervention era. 4.5. Conclusions Our data demonstrated that RBBB was still associated with poor left ventricular function and high 30-day mortality in patients with anterior AMI even in the coronary intervention era. Patients with anterior AMI and RBBB should be recognized early and receive prompt and aggressive treatment. References [1] Godman MJ, Lassers BW, Julian DG. Complete bundle-branch block complication in acute myocardial infarction. N Engl J Med 1970;282: 237–40. [2] Roos JC, Duning AJ. Right bundle-branch block and left axis deviation in acute myocardial infarction. Br Heart J 1970;32:847–51. [3] Col JJ, Weinberg SL. Incidence and mortality of intraventricular conduction defects in acute myocardial infarction. Am J Cardiol 1972;29:344–50. [4] Scheinman M, Brenman B. Clinical and anatomic implication of intraventricular conduction block in acute myocardial infarction. Circulation 1972;46:753–60. [5] Scheidt S, Killip T. Bundle-branch block complicating acute myocardial infarction. JAMA 1972;222:919–24. [6] Atkins JM, Leshin SJ, Blomqvist CG, Mullins CB. Ventricular conduction blocks and sudden death during acute myocardial infarction: potential indication for pacing. N Engl J Med 1973; 288:281–4. [7] Hindman MC, Wagner GS, JaRo M, et al. The clinical significance of bundle branch block complicating acute myocardial infarction: I. Clinical characteristics, hospital mortality, and 1-year follow-up. Circulation 1978;58:679–88.
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