Journal of the American College of Cardiology Vol. 62, No. 11, 2013� 2013 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jacc.2013.04.060

CLINICAL RESEARCH Coronary Artery Disease

Right, But Not Left, Bundle Branch BlockIs Associated With Large Anteroseptal Scar

David G. Strauss, MD, PHD,* Zak Loring, MD,*y Ronald H. Selvester, MD,z Gary Gerstenblith, MD,xGordon Tomaselli, MD,x Robert G. Weiss, MD,x Galen S. Wagner, MD,k Katherine C. Wu, MDxSilver Spring and Baltimore, Maryland; Durham, North Carolina; and Long Beach, California

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his study sought to test the hypothesis that right bundle branch block (RBBB) patients have larger scar size thanleft bundle branch block (LBBB) patients do.

Background A

proximal septal perforating branch of the left anterior descending (LAD) coronary artery most commonly perfusesthe right bundle branch and left anterior fascicle, but not the left posterior fascicle. Thus, proximal LAD occlusionsshould cause RBBB, not LBBB.

Methods W

e performed electrocardiograms and magnetic resonance imaging for scar quantification in 233 patients with leftventricular (LV) ejection fraction �35% who were receiving primary prevention implantable cardioverter-defibrillators(ICD cohort). Scar size and location were compared among patients with RBBB, LBBB, nonspecific LV conductiondelay, and QRS <120 ms. A second cohort of 20 hypertrophic cardiomyopathy patients undergoing alcohol septalablation was studied to determine whether controlled infarction in a proximal LAD septal perforator caused RBBB orLBBB.

Results In

the ICD cohort, LV ejection fraction was similar between RBBB and LBBB patients (24.9% vs. 25.0%; p ¼ 0.98);however, RBBB patients had significantly larger scar size (24.0% vs. 6.5%; p < 0.0001). Patients with nonspecific LVconduction delay or QRS <120 ms had intermediate scar size (12.9% and 14.4%, respectively). Those with RBBB(compared with LBBB) were more likely to have ischemic heart disease (79% vs. 29%; p < 0.0001). In the alcoholseptal ablation cohort, 15 of 20 patients (75%) developed RBBB, but no patients developed LBBB.

Conclusions In

patients with LV ejection fraction �35%, RBBB is associated with significantly larger scar size than LBBB is, andocclusion of a proximal LAD septal perforator causes RBBB. In contrast, LBBB is most commonly caused bynonischemic pathologies. (J Am Coll Cardiol 2013;62:959–67) ª 2013 by the American College of CardiologyFoundation

A conventional clinical concept is that new onset leftbundle branch block (LBBB) or right bundle branch block(RBBB) that occurs with acute myocardial infarction (MI) is

ineering, Center for Devices and Radiological

inistration, Silver Spring, Maryland; yDuke

rham, North Carolina; zMemorial Hospital

rnia; xDivision of Cardiology, Department of

stitutions, Baltimore, Maryland; and the kDuke

North Carolina. The mention of commercial

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implied endorsement of such products by the

an Services. This project was supported in part

istration’s Critical Path Initiative; Donald W.

enter at Johns Hopkins University; and the

d Institute, National Institutes of Health

2 to Dr. Tomaselli, and #HL61912 to Dr.

software tool, Cinetool, was obtained through

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s to use the gray zone methodology described in

rted that they have no relationships relevant to

2012; revised manuscript received April 1, 2013,

associated with massive MI (1–3). However, the relationbetween coronary artery and bundle branch anatomy suggeststhat very different relationships should exist between MIlocation and size with bundle branch block type. A priornecropsy study demonstrated that the proximal left anteriordescending coronary artery (LAD) septal perforators perfusethe right bundle branch and the anterior fascicle of the leftbundle branch in 90% of cases, whereas the right coronaryartery (via the atrioventricular-nodal artery) perfuses the

See page 968

posterior fascicle of the left bundle branch in 90% of cases(4). There is dual blood supply to each of these fascicles in40% to 50% of cases (4). This means that proximal LADocclusions could cause RBBB and/or left anterior fascicularblock. However, both proximal LAD and right coronaryartery occlusions would be required typically for MI to causeLBBB. Instead, as originally described by Lenègre (5), his-topathology studies demonstrated that the disruption of the

Abbreviationsand Acronyms

CMR-LGE = cardiac

magnetic resonance late

gadolinium enhancement

CRT = cardiac

resynchronization therapy

ECG = electrocardiography/

electrocardiogram(s)

ICD = implantable

cardioverter-defibrillator

LAD = left anterior

descending coronary artery

LV = left ventricle/

ventricular

LVCD = left ventricular

conduction delay

LBBB = left bundle branch

block

MI = myocardial infarction(s)

RBBB = right bundle branch

block

RCA = right coronary artery

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left bundle branch almost alwaysoccurs at its junction with themain bundle, often with histo-logical findings of fibrosis orsclerosis with occasional calcifi-cation (5–7). Furthermore, at thislocation, the left bundle branch canbe compressed between connectivetissue of the central fibrous bodyand the base of the ventricularseptum (5–7), especially whensubjected to mechanical strainfromahypertrophied or dilated leftventricle (LV).

In chronic cardiomyopathy, pro-longed QRS duration is associ-ated with increased mortality (8);however, the cause of the associ-ation likely differs depending onthe conduction type. In LBBB,the large delay between activationof the interventricular septumand LV free wall leads to dyssyn-chronous and inefficient LV

contraction (9). In RBBB, activation of the LV is normal;however, increased mortality may be due to the associationof RBBB and large anteroseptal MI that portend poorprognosis.

Cardiac magnetic resonance (CMR) with late gadoli-nium enhancement (LGE) is the gold standard foridentifying the location of and quantifying the amount ofmyocardial scar caused by prior MI or nonischemiccauses of cardiomyopathy (10). In a cohort of chronicischemic and nonischemic cardiomyopathy patients, weused CMR to test the hypothesis that RBBB patientshave a larger scar burden than LBBB patients do becauseRBBB patients have a higher prevalence of proximalLAD MI and less frequent nonischemic pathologies. Asa proof-of-concept group, we also studied the ECGcharacteristics of a cohort of patients with the obstructiveform of hypertrophic cardiomyopathy who underwentpercutaneous alcohol septal ablation of the proximalseptal perforator and could thus serve as a controlledmodel of proximal anteroseptal infarction.

Methods

ICD cohort population. Patients referred clinically toJohns Hopkins Medical Institutions for implantablecardioverter-defibrillator (ICD) placement for primaryprevention of sudden cardiac death were prospectivelyenrolled between November 2003 and December 2010(11). The population has been described previously(11–14). All patients had to have LV ejection frac-tion �35%, coronary angiography, no other indications forICD placement, and no contraindications to CMR.

Patients were classified as “nonischemic” if they had nohistory of MI or revascularization and no evidence ofcoronary artery stenoses >50% of 2 or more epicardialvessels or left main or proximal LAD stenosis >50%.Other patients were classified as “ischemic.” All MI hadoccurred >1 month prior to enrollment. This studyprotocol was approved by the Johns Hopkins InstitutionalReview Board. All patients gave written informed consent.

Hypertrophic cardiomyopathy alcohol septal ablationcohort. Patients with hypertrophic cardiomyopathy referredclinically to Johns Hopkins Medical Institutions for percu-taneous alcohol septal ablation were enrolled betweenDecember 2000 and November 2005 as part of a single-center prospective cohort of CMR before and after septalablation. This study protocol was approved by the JohnsHopkins Institutional Review Board. All patients gavewritten informed consent.

CMR acquisition and analysis in ICD cohort. Patientsunderwent cine and CMR-LGE imaging using a 1.5-Tscanner (GE Signa CV/I, GE Medical Systems, Milwau-kee, Wisconsin; or Siemens Avanto, Siemens MedicalSolutions. Malvern, Pennsylvania). Image analysis was per-formed using custom research software CINEtool (GEHealthcare, Milwaukee, Wisconsin). Cine images were usedto measure ejection fraction and volumes, and LGE imageswere used to measure total scar size for the entire LV. TheLGE area was outlined, and pixels with signal intensity>50% of the maximum within the LGE area were labeled asscar “core” (12,14). A region of normal myocardium withoutartifacts was then selected and the peak signal intensity withinthe normal myocardium was determined. Myocardium withsignal intensity greater than peak remote signal intensitybut <50% of maximal signal intensity within the LGE regionwas labeled the “gray” zone to represent the heterogeneousperi-scar zone (12,14). Total scar size was expressed ascore þ1/2 gray zone as a percentage of total LV mass (14).

Scar location was determined using the American HeartAssociation’s 17-segment model of the LV (15). Patientswith ischemic cardiomyopathy were grouped into thosehaving infarct with a(n) LAD, right coronary artery (RCA),and/or left circumflex infarction pattern (15). Patients withnonischemic cardiomyopathy were grouped into 6 patterns:1) no scar present; 2) scar confined to the mid-wallmyocardium; 3) scar confined to the epicardium; 4) scarconfined to the endocardium; 5) transmural scar; and 6) scarat the right ventricular insertion points based on previouslydescribed patterns (16). Scar transmural involvement in eachof the 17 segments was graded on a 0-to-4-point scale asdescribed previously: 0 for 0% hyperenhancement; 1 for 1%to 25% hyperenhancement; 2 for 26% to 50% hyper-enhancement; 3 for 51% to 75% hyperenhancement; and 4for 76% to 100% hyperenhancement (17).

ECG analysis for both cohorts. ECG at the time of CMRwere analyzed according to previously specified criteria(14,18,19):

Table 1 Baseline Characteristics of ICD Cohort

RBBB(n ¼ 19)

LBBB(n ¼ 45)

LVCD(n ¼ 35)

QRSd <120 ms(n ¼ 134)

p ValueRBBB vs. LBBB

Age, yrs 59.1 � 7.8 59.7 � 11.4 64.2 � 12.6 54.6 � 12.2 0.85

Female 14 (74) 29 (64) 27 (77) 109 (81) 0.48

LVEF, % 24.9 � 8.7 25.0 � 9.0 26.1 � 8.9 28.3 � 8.9 0.98

Ischemic 15 (79) 13 (29) 25 (71) 78 (58) <0.0001*

QRS duration, ms 150.3 � 16.8 162.2 � 20.3 130.7 � 14.1 98.3 � 10.7 0.028*

Ethnicity 0.27

Caucasian 15 (79) 34 (76) 27 (77) 86 (64)

African American 3 (16) 10 (22) 8 (23) 42 (31)

Other 1 (5) 0 (0) 0 (0) 5 (4)

NYHA functional class 0.095*

I 4 (21) 2 (4) 9 (26) 43 (32)

II 7 (37) 16 (36) 4 (11) 68 (51)

III 8 (42) 27 (60) 22 (63) 23 (17)

LVEDV/BSA, ml/m2 114.9 � 34.4 137.2 � 50.0 131.4 � 43.1 115.6 � 36.3 0.081*

LVESV/BSA, ml/m2 89.0 � 37.3 105.9 � 51.7 98.8 � 40.5 84.8 � 34.6 0.20*

LV mass/BSA, ml/m2 73.5 � 22.5 82.1 � 32.6 78.9 � 27.0 70.2 � 20.8 0.30*

Values are mean � SD or n (%). Bold values are statistically significant. *p < 0.05 for groupwise comparison among 4 groups.BSA ¼ body surface area; ICD ¼ implantable cardioverter-defibrillator; LBBB ¼ left bundle branch block; LV ¼ left ventricle/ventricular; LVCD ¼ left

ventricular conduction delay; LVEDV ¼ left ventricular end-diastolic volume; LVEF ¼ left ventricular ejection fraction; LVESV ¼ left ventricular end-systolic volume; NYHA ¼ New York Heart Association; RBBB ¼ right bundle branch block; QRSd ¼ QRS duration.

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� LBBB: QRS duration �140 ms (men) or �130 ms(women), QS or rS complex in leads V1 and V2 withmid-QRS notching/slurring in 2 of the leads I, aVL,V1, V2, V5, or V6;

� RBBB: QRS duration �120 ms with rR’ or qRcomplex in lead V1 and a wide S wave in lead I(patients with left axis deviation [�180 to �45�] wereclassified as left anterior fascicular block þ RBBB;

� Nonspecific LV conduction delay (LVCD): QRSduration �120 ms and QS or rS complex in lead V1,but not meeting LBBB or RBBB criteria; and

� QRS duration <120 ms.

Statistical analysis. Variables following Gaussian distribu-tions were compared by ECG conduction type with parame-tric measures (2-sample Student t test, 1-way analysis ofvariance), whereas those not following Gaussian distributionswere analyzed nonparametrically (Wilcoxon rank sum,nonparametric 1-way analysis of variance). Categorical vari-ables were evaluated by chi-square. Analysis was performedseparately comparing RBBB and LBBB patients andcomparing all 4 ECG conduction types. The p values <0.05were considered significant.

Results

Of the 235 primary prevention ICD patients available foranalysis, 2 were excluded because only ventricular-pacedECG were available. The remaining 233 (77% were men)had a mean age of 57 years, a mean LV ejection fraction of27%, 56% ischemic etiology, and a distribution of New YorkHeart Association heart failure classes of 25% class I, 41%class II, and 34% class III. There were no differences in age,

sex, ethnicity, heart failure class, or LV ejection fractionbetween RBBB and LBBB patients (Table 1). However,there were significant differences in scar size, anatomic scarlocation, and prevalence of ischemic versus nonischemiccardiomyopathy. In addition, there was a trend toward largerLV end-diastolic volume in LBBB patients.Right versus left bundle branch block. Figure 1 shows theCMR-LGE image of a RBBB patient with ischemiccardiomyopathy and a large anteroseptal scar involving 45%of the LV, and Figure 2 shows the CMR-LGE of a LBBBpatient with nonischemic cardiomyopathy and no scar. Asa group, the mean scar size in RBBB patients was signi-ficantly greater than in LBBB patients (24.0% vs. 6.5%;p < 0.0001), whereas patients with nonspecific LVCD orQRS duration <120 ms had intermediate scar size (12.9%and 14.4%, respectively) (Table 2). Of note, even thoughanalysis in this study was performed with the pre-specifiedstrict LBBB criteria (14,18,20), defining LBBB withconventional LBBB criteria (QRS �120 ms, with QS waveor rS complex in lead V1) still resulted in a large differencein scar size between LBBB (9.3 � 10.2% LV) and RBBB(24.0 � 15.7% LV) patients (p < 0.0001).

The difference in scar size was partially explained bya higher prevalence of ischemic cardiomyopathy in RBBBcompared with LBBB patients (79% vs. 29%; p < 0.0001).However, among ischemic cardiomyopathy patients, a largerscar size persisted among those with RBBB versus thosewith LBBB (28.5% vs. 14.7%; p ¼ 0.006). The scardistribution in each of the 17 segments is shown in polarplots in Figure 3. The right bundle branch runs approxi-mately through segment 8 (mid-anteroseptal wall), whichwas the segment with the highest transmural scar gradeamong the RBBB patients, and was significantly higher than

Figure 1 CMR-LGE and ECG of RBBB Patient With Ischemic Cardiomyopathy and Large Anteroseptal Scar

This patient had extensive scarring (arrows) by cardiac magnetic resonance late gadolinium enhancement (CMR-LGE) (A) from a prior proximal left anterior descending coronary

artery occlusion. The patient’s electrocardiogram (ECG) (B) showed a right bundle branch block (RBBB) with left anterior fascicular block.

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the mid-anteroseptal scar grade (measure of scar transmuralinvolvement) in LBBB patients (2.47 vs. 0.89; p ¼ 0.001).

When considering only ischemic patients, 11 of 15 (73%)RBBB patients had scar consistent with LAD occlusions(2 of whom also had scar in a second territory), and theaverage scar size was 34.8% of the LV (range 19% to 50%LV) for LAD-only scar. Of the 4 other ischemic RBBBpatients, 2 were RCA-territory scars, 1 was a left circumflexscar, and 1 was not a typical ischemic pattern (scar near rightventricular insertion points). In contrast, among the 13ischemic LBBB patients, there were 3 with scar patternsconsistent with LAD þ RCA, 6 LAD-only, 2 RCA-only,and 2 left circumflex-only. Prior necropsy studies havesuggested that both LAD and RCA infarcts would usuallybe required for MI to be the sole cause of a LBBB, and it isunlikely for a LAD-only MI to cause a LBBB. Among the 6LAD-only LBBB patients, only 1 of them had a large scar(35% LV), whereas the remainder had scar sizes not morethan 16% of the LV (range: 5% to 16%). This suggests that

in at least 5 of these 6 cases, the LAD scar was not likely thedirect cause of the LBBB, but rather the LBBB developeddue to stress and strain on the left bundle fibers associatedwith LV dilation and progressive cardiomyopathy. Indeed,there was a trend toward larger LV end-diastolic volume(corrected for body surface area) in LBBB versus RBBBpatients overall (137.2 vs. 114.9 ml/m2; p ¼ 0.081).

Among nonischemic patients, 0 of 4 RBBB patients hadno scar, whereas 20 of 32 (63%) LBBB patients had no scar(p ¼ 0.017 for comparison). There was no significantdifference in the scar patterns (mid-wall, epicardial, endo-cardial, transmural vs. right ventricular insertion) in RBBBversus LBBB patients.Alcohol septal ablation. QRS duration was normal in allhypertrophic cardiomyopathy patients prior to the septalablation. Subsequent to the alcohol septal ablation ofa proximal LAD septal perforator, 15 of 20 (75%) developedRBBB, whereas no patients developed LBBB. Figure 4shows the ECG of a patient before and after alcohol

Figure 2 CMR-LGE and ECG of LBBB Patient

This patient had nonischemic cardiomyopathy and no scar present by cardiac magnetic resonance late gadolinium enhancement (CMR-LGE) (A). The patient’s ECG (B) showed

left bundle branch block (LBBB). Abbreviations as in Figure 1.

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septal ablation that developed RBBB. The patients’ CMR-LGE image shows a focal area of LGE in the basalseptum representing the area of necrosis causing RBBB.

Among those who developed RBBB, 3 of 15 also devel-oped left anterior fascicular block. QRS duration increasedby 42 � 11 ms among those developing RBBB (p < 0.0001compared with baseline), whereas there was no significantchange in QRS duration among those that did not developRBBB (p ¼ 0.24). No patients developed left anteriorfascicular block without RBBB.

Discussion

Our study supports the premise that RBBB has a strongassociation with large anteroseptal scar in cardiomyopathypatients, and occlusion of a proximal LAD septal perforatorcausesRBBB. In contrast, themajority of LBBBpatients have

nonischemic cardiomyopathies and, even among those withischemic cardiomyopathy, LBBB patients have significantlylower overall scar burden than RBBB patients do, whereasLVCD and QRS duration <120 ms patients have interme-diate scar sizes. These results oppose the conventional clinicalconcept that LBBB is caused by massive septal infarction.Instead, LBBB is more likely caused by a combination ofsclerosis and fibrosis combined with mechanical strain on theleft bundle fibers near the left bundle junction with the mainbundle, where the conduction fibers are sandwiched betweenthe connective tissue of the central fibrous body and the base ofthe ventricular septum (5–7).However, it is possible that theseobservations are an artifact of survival bias. The relationshipbetween proximal LAD occlusions and RBBB (but notLBBB) was further confirmed by our cohort with hypertro-phic cardiomyopathy in whom alcohol ablation of a proximalLAD septal perforator led to RBBB in 75% of patients, but

Table 2 CMR-LGE Scar Size of ICD Cohort

RBBB LBBB LVCD QRSd <120 msp Value

RBBB vs. LBBB

All 19 45 35 134

Scar size, %LV 24.0 � 15.1 6.5 � 9.4 12.9 � 10.0 14.4 � 13.7 <0.0001*

Scar core, %LV 17.8 � 11.1 4.3 � 6.1 9.4 � 7.1 10.6 � 10.4 <0.0001*

Scar gray, %LV 12.3 � 9.2 4.2 � 7.0 7.0 � 6.4 7.6 � 7.9 <0.0001*

Ischemic 15 13 25 77

Scar size, %LV 28.5 � 13.7 14.7 � 9.7 17.4 � 8.2 22.5 � 11.0 0.006*

Scar core, %LV 21.0 � 10.2 10.0 � 6.2 12.6 � 5.7 16.7 � 8.8 0.002*

Scar gray, %LV 14.7 � 8.6 9.0 � 7.3 9.5 � 6.0 11.6 � 7.1 0.072

Nonischemic 4 32 10 57

Scar size, %LV 7.3 � 4.7 3.2 � 7.1 1.8 � 1.9 3.4 � 8.1 0.27

Scar core, %LV 5.7 � 3.4 2.0 � 4.3 1.4 � 1.6 2.3 � 5.4 0.110

Scar gray, %LV 3.1 � 4.5 2.3 � 6.0 0.8 � 0.8 2.2 � 5.4 0.80

Values are n or mean � SD. Bold values are statistically significant. *p < 0.05 for groupwise comparison among 4 groups.CMR-LGE ¼ cardiac magnetic resonance late gadolinium enhancement; %LV ¼ percentage of left ventricle; other abbreviations as in Table 1.

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not to LBBB. This evidence that LAD occlusions causeRBBB, but not LBBB, has important potential clinicalimplications for primary prevention ICD and cardiacresynchronization therapy (CRT) patients, such as those inthis study, but also potentially for acute MI patients.

Figure 3 Segmental Scar Distribution in the ICD Cohort

Polar plots show the average transmural scar extent within each of the 17 American Hea

hyperenhancement; 1 for 1% to 25% hyperenhancement; 2 for 26% to 50% hyperenhanc

hyperenhancement) (17). The figure is scaled from no scar (light yellow) to a transmura

segment 8 (mid-anteroseptal), which had the highest scar grade of any segment in RBBB

conduction delay; QRSd ¼ QRS duration; other abbreviations as in Figures 1 and 2.

CRT studies performed in the past decade were limitedby the lack of distinction between ventricular block types.CRT trials enrolled patients with QRS duration �120 ms(without distinction between conduction types) and showedthat CRT reduced heart failure symptoms, heart failure

rt Association–defined myocardial segments graded on a 0-to-4-point scale (0 for 0%

ement; 3 for 51% to 75% hyperenhancement; and 4 for 76% to 100%

l scar grade of 2.5 (dark red). Note that the right bundle branch runs through

patients. ICD ¼ implantable cardioverter-defibrillator; LVCD ¼ left ventricular

Figure 4 ECG and CMR-LGE of Patient Developing RBBB After Alcohol Septal Ablation

This hypertrophic cardiomyopathy patient had a baseline ECG (A) showing left ventricular hypertrophy, but not bundle branch block. Alcohol septal ablation was performed in

a proximal left anterior descending coronary artery septal perforator leading to necrosis highlighted by arrows in the CMR-LGE image (B). Post-septal ablation ECG (C) showed

that RBBB developed. Abbreviations as in Figure 1.

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hospitalization, and mortality (21–26). However, morerecent analysis has suggested that the benefit from CRT isdriven by LBBB patients (26–28), especially in theMADIT-CRT (Multicenter Automated DefibrillatorImplantation Trial) that enrolled New York Heart Associ-ation class I and II patients (27). In that trial, neither RBBBpatients nor nonspecific LVCD patients benefited fromCRT. Furthermore, large outcome studies of Medicarepatients demonstrated that, among CRT recipients,mortality is highest with RBBB, intermediate with LVCD,and lowest with LBBB (29,30). CRT likely benefits LBBBpatients most because RBBB and LVCD patients havenormal Purkinje activation of the LV, but poor prognosiswith RBBB may also be due to RBBB association with largescar burden, as demonstrated in the present study.

Our results have potential implications for acute MIpatients, as well. Prior studies have described the associationbetween new onset LBBB and occlusion of the proximalLAD artery and large MI size (2). However, this was basedon remote studies using Q waves in leads V1 to V3 todetermine anteroseptal MI location and creatine kinase–measured infarct size (1). Recent studies using CMR-LGEhave demonstrated that in LBBB, large R waves (not Qwaves) in leads V1 to V3 represent anteroseptal MI (14,18).As discussed previously, post-mortem studies support theobservation that proximal LAD septal perforators mostcommonly perfuse the right bundle branch and the anteriorhalf of left bundle branch, whereas the RCA (via theatrioventricular-nodal artery) most commonly perfuses theposterior half of the left bundle branch (4). Thus, proximalLAD occlusions can cause RBBB and/or left anteriorfascicular block; however, both proximal LAD and RCAocclusions would typically be required for infarcts to be thecause of LBBB. In addition, some patients diagnosed withLBBB by conventional ECG criteria do not have activationconsistent with LBBB and the recently proposed strictLBBB criteria (14,18,20) used in the present study should beassessed in future studies in patients presenting with symp-toms of acute coronary syndromes.

Our data from the hypertrophic cardiomyopathy patientsundergoing septal ablation of a proximal LAD septalperforator support this concept as 15 of 20 patients developedRBBB (with 3 developing left anterior fascicular block inaddition to RBBB), whereas no patients developed LBBB.This is consistent with previous studies (31,32). Qin et al.(31) reported that 62% of patients developed RBBB afterseptal ablation, whereas 6% developed LBBB. It is possiblethat the limited number of patients supposedly developingLBBB did not actually develop LBBB, but rather left ante-rior fascicular block that caused the patients to meetconventional ECG criteria for LBBB, but they would nothave met strict criteria for LBBB used in this study (20).Study limitations. All patients enrolled in the ICD cohortportion of this study had an ejection fraction �35% and met

criteria for primary prevention ICD. Thus, the results cannotnecessarily be extrapolated outside of this population.Although we comment on how our findings might translateto patients presenting with bundle branch block and acuteMI, this should be interpreted with caution and requiresfurther study. Although the subgroup comparison of is-chemic patients still demonstrates smaller scar in the LBBBgroup, this may be an artifact of survival bias; specifically, thatpatients with large anterior MI who develop or have LBBBare less likely to survive long enough to qualify for an ICD.Studying hypertrophic cardiomyopathy patients undergoingalcohol septal ablation of a proximal LAD septal perforatordid allow us to investigate the direct effect of proximal LADocclusion in an acute setting; however, directed alcoholinfusion down a septal perforator may not be representa-tive of naturally occurring LAD coronary occlusions.

Conclusions

In a chronic cardiomyopathy cohort, RBBB is associatedwith ischemic cardiomyopathy and large anteroseptal scar,whereas LBBB is associated with nonischemic etiologies.The large myocardial scar in RBBB patients may explainwhy they have even worse mortality than do nonspecificLVCD patients receiving CRT. This study highlights thatthe LAD branches perfuse the right bundle branch and leftanterior fascicle, but not the entire left bundle branch.Future clinical prognostic studies should specifically distin-guish between RBBB and LBBB patients rather thanconsider them homogeneously. Assessment of scar burden asanother risk factor may also be of value.

AcknowledgmentsThe authors thank research coordinators Barbara Butcher,Jeannette Walker, Sanaz Norgard, and Angela Steinberg;and magnetic resonance technologist Terry Frank for theirefforts. The authors are also grateful to the patients for theirparticipation.

Reprint requests and correspondence: Dr. David G. Strauss,FDA, Center fot Devices and Radiological Health, 10903 NewHampshire Avenue, WO62-1126, Silver Spring, Maryland 20993.E-mail: david.strauss@fda.hhs.gov.

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Key Words: ischemic heart disease - left bundle branch block -

myocardial infarction - nonischemic cardiomyopathy - right bundlebranch block.