Exercise-Induced Bundle Branch Block

VICTOR S. WAYNE, MBBS (HONS), FRACP, RICHARD L. BISHOP, MD,

LINDA COOK, LPN, and DAVID H. SPODICK, MD, DSc

Exercise-induced bundle branch block (BBB) is poorly understood. An investigation was made of its clinical, electrocardiographic, coronary angio- graphic, and myocardial scintigraphic character- istics, with follow-up data in 16 patients, aged 59 f 9 (mean f standard deviation) years, 11 who had left BBB and 5 who had right BBB. Fourteen had a preexisting baseline electrocardiographic abnor- mality; 11 had either incomplete BBB or nonspecific intraventricular conduction delay. Heart rates at onset of exercise BBB varied from 70 to 166 beats/min and in 9 patients the rates at BBB onset and offset appeared to be related, occurring within 6 beats/min of each other. Coronary artery disease (CAD) was diagnosed In 10 patients, cardiomyop-

athy in 2, and probable coronary spasm in 2. One patient had ventricular arrhythmias of uncertain origin, and 1 appeared to have no cardiac disease. Three patients had reversible thallium perfusion defects consistent with ischemia concurrent with developing BBB. The 3 patients in whom exercise BBB persisted all had CAD. Over a mean of 26 months of follow-up, only 1 patient had a morbid cardiac event-nonfatal myocardiai infarction-and 2 died from noncardiac causes. Thus, exercise BBB primarily occurs in the context of cardiac disease, most commonly CAD, and concurrent ischemia may be demonstrable; the presence of “rate relation” does not militate against CAD.

There are well-recogniz,ed electrocardiographic (ECG) responses to myocardial ischemia, but little information other than case reports is available on the diagnostic and prognostic significance of exercise-induced bundle branch block (BBB). We assessed the clinical data, available coronary angiographic and scintigraphic in- formation, and follow-up in 16 patients with this phe- nomenon.

Nethods

Patient selection and exercise testing: Of 4,100 subjects who had exercise tests between February 1977 and February 1982,16 (0.39%) had exercise-induced complete left or right BBB. Twelve were men and 4 were women, aged 45 to 76 years (mean 59 f 9). Fourteen had maximal exercise with the standard and 2 with the modified Bruce protocol.

BBB criteria: Left: QRS 1 0.13 second; absent septal q; small or absent R waves with wide S waves in medial precor- dial leads.

Right: QRS I 0.12 secon.d; R’ in VI after 0.08 second; broad S in lead 1 and lateral precordial leads.

From the Division of Cardiology, St. Vincent Hospital, Worcester, Massachusetts, and the University of Massachusetts Medical School, Worcester, Massachusetts. M.anuscript received February 22, 1983; revised manuscript received May 2, 1983, accepted May 4, 1983.

Address for reprints: David H. Spodick, MD, Director, Division of Cardiology, St. Vincent Hospital, 25 Winthrop Street, Worcester, Massachusetts 0 1604.

Coronary angiography and myocardial scintigraphy: Six patients had coronary angiography. Significant disease was defined as 150% luminal reduction in a major branch.

Eight patients had thallium-201 scintigraphy; perfusion was analyzed regionally as normal, reversible (consistent with ischemia), or irreversible (consistent with scarring).

Follow-up: Follow-up data were obtained from patients and physicians. Morbid cardiac events were defined as those that required hospitalization of the patient.

Results

Table I lists patient profiles, medications, test indi- cations, baseline electrocardiograms, and exercise data.

Eleven patients had left BBB and 5 had right BBB during exercise.

Left BBB (11 patients): Nine patients had a prior ECG abnormality: 6 either incomplete left BBB or nonspecific intraventricular conduction delay (IVCD) (QRS >_ 0.10 second), 1 nonspecific ST-T changes, 1 left ventricular hypertrophy, and 1 left-axis deviation and old inferior infarction.

Heart rates at left BBB onset varied from 70 to 166 beats/min and at offset from 66 to 131 beats/min. In 7 cases, offset rate was within 8 beats of onset rate. In 3 cases, onset and offset rates differed >25 beats. In 1 case, left BBB persisted beyond the recovery phase. Exercise was stopped in 1 patient because of onset of left

204 EXERCISE-INDUCED BUNDLE BRANCH BLOCK

TABLE I Clinical Data

HR at BBB HR at BBB

Age (yr) Indication Pretest Exercise Onset Offset Test Final Case & Sex Medications for Test ECG BBB (beats/min) (beatsimin) End Point Diagnosis

: 61M N AP (HT) IVCD Left 65 AP CAD 72M M, quinidine Palpitations (HT) IVCD, LAD Right 1:: 100 F, D

B 45M P Chest pain IVCD, LVH Left 95 90 ZD 63M N, P, T AP (Ml X 2) IVCD Left 101 72 ;D CAD

: ;Ei iisopyramide Chest pain Normal Left 166 131 TArget HR Normal

AP (Ml) Inc. LBBB Left 96 68 55M P, T AP (HT) Inc. LBBB, PMI Right

Leg fatigue CAD

3 10’0’ Persisted F, leg pain CAD

67M N, tolbutamide AP (Ml) Inc. RBBB, LAD Right Persisted F CAD 9 53F N, P, furosemide AP Left

:: 51F T,M A? (HT)

;Ti;changes Right :z :: :

Cor spasm

66F 12 60M N, P ‘*’

AP, D Normal Left 70 66 D ZrDspasm AP (Ml) Inc. RBBB, LAD Right ‘75-115 75-l 15 Target HR CAD

;: 55M N. P Chest pain LVH Left 72 LBBB onset PMD 64M P AP (HT) IVCD, LAD Left ;: Persisted AP CAD

15 46M N, P ;p’ [I$

IVCD, LAD, PLMI Left 138 aa D CAD 16 76F N, cimetidine LAD, Ml Left ‘74-128 74-l 28 Target HR CAD

l The exact rates of Onset and offset of exercise EBB in these 2 patients could not be determined, but are known to be within 6 beats/min of each other.

AP = angina pectoris; BBB = bundle branch block; CAD = coronary artery disease; Cor spasm = coronary artery spasm; D = dyspnea; ECG = electrocardiogram; F = fatigue; HR = heart rate; HT = prior hypertension; Inc. = incomplete; IVCD = intraventricular conduction delay; LAD = left-axis deviation; LVH = left-ventricular hypertrophy; M = methyldopa; Ml = prior myocardial infarction; N = nitrates; P = propranolol; PLMI = posterolateral my-dial infarction; PMD = primary myocardial disease: PMI = posterior myocardial infarct; T = thiiide diuretic; VA = ventricular arrhythmias.

BBB. The onset rate of left BBB displayed no obvious relation to the maximum heart rate achieved with symptom-limited testing. In 4 patients, onset rate was 57 beats of maximum rate; 7 patients exercised to 25 to 60 beats/min higher than the onset rate of left BBB.

Right BBB (5 patients): All 5 patients had a prior electrocardiographic abnormality, 3 incomplete right BBB and 2 IVCD. Onset rates of right BBB varied from 77 to 130 beats/min. In 2 patients, BBB persisted past the recovery phase and in 3, right BBB offset occurred at 85 to 100 beatslmin; in 2 of them, onset and offset rates were almost identical. One patient had right BBB several seconds before the end of the test; the other 4 reached 23 to 61 beats/min higher than at BBB onset.

There were no apparent differences between patients who had left versus right BBB with regard to age, sex, and clinical characteristics.

Coronary angiography: Angiography was per- formed in 6 patients, 4 with exercise left BBB and 2 with right BBB. Two patients had severe 3-vessel coronary artery disease (CAD) with diminished left ventricular function. One (Patient 14) had intermittent left BBB during contrast injection. One patient with exercise right BBB (Patient 7) had right coronary disease-50% proximal stenosis and 90% distal stenosis near the origin of the atrioventricular nodal artery. Patient 13 had normal coronary arteries but mild anterolateral left ventricular hypokinesia. He had left ventricular hy- pertrophy on the resting electrocardiogram and a nor- mal echocardiogram and is regarded as having primary myocardial disease. Left BBB developed several times during catheterization, apparently related to positional changes and contrast injection; heart rates for left BBB onset and offset were not recorded. Two.patients had normal coronary arteries and LV function.

Myocardial scintigraphy: Six patients, 4 with left and 2 with right exercise BBB, had exercise thallium- 201 myocardial scintigraphy. Three had reversible perfusion defects, 2 of which were associated with ad- ditional irreversible defects. Ischemic areas were pos- terolateral in 1 and anteroseptal in 2; 1 (Patient 5) had a normal study and 2 had irreversible perfusion defects only, 1 septal and 1 apical.

Follow-up: Patients were followed up for 7 to 69 months (mean 28). Two died, 1 at 7 months after exer- cise testing from carcinoma. He had a previous myo- cardial infarction. The other, who also had had a pre- vious infarction, died from glioma 32 months after testing. Neither had any morbid cardiac events between exercise testing and death. Of the remaining 14 patients, Patients 4 and 14 had coronary bypass shortly after testing without postoperative morbid cardiac events. One patient (Patient 16) had an infarct during follow-up study. Three patients, all with documented CAD, have stable angina.

In summary, clinical and investigational data yielded diagnoses of CAD in 10 patients and myocardial disease in 2. Two had angina1 pain and fluctuating ST-T changes but normal coronary angiograms, suggesting coronary spasm (heightened by an abnormal exercise thallium scan in 1). One patient (Patient 2) had ven- tricular arrhythmias without other evidence of cardiac disease. Only 1 was considered normal.

Discussion

There are very few data, and thus there is no con- sensus, regarding the significance of exercise-induced complete BBB. This is surprising, as BBB renders the ECG response to exercise inconclusive, producing a diagnostic and management dilemma.

Our study, to our knowledge the largest reported series of exercise BBB, examines several questions:

August 1983 THE AMERICAN JOURNAL OF CARDIOLOGY Volume 52 205

What are the clinical and ECG characteristics of pa- tients with exercise-induced BBB? Does it represent a hitherto uncharacterized response to ischemia? Is it more prevalent in patients with than without CAD, or is it a “rate-related” electrical phenomenon not neces- sarily occurring in thle context of CAD? What is its prognostic significance?

Compared with the scarce data concerning exercise BBB, some informat:ion is available on intermittent BBB unrelated to exercise. Coronary angiography in patients with intermittent BBB demonstrates both normal and diseased coronary arteries. Lewis et al’ re- ported on 12 patients, with left BBB; of 4 with inter- mittent left BBB, 2 had significant CAD, 1 normal coronary arteries, and 1 patent ductus. In another re- port,” 5 had normal coronary arteries, 1 significant CAD, and another idiopathic cardiomyopathy. In another series,3 among 5 patients with intermittent left BBB, 3 had normal coronary arteries and 2 had single-vessel CAD. Scintigraphy in this study, using rubidium-81 and potassium-43, produced a number of false-positive resting perfusion scans, which returned to normal with exercise in patients wi.th angiographically normal cor- onary arteries versus those with CAD. Yet there were some equivocal exercise scintigraphic results. Of 8 pa- tients with intermittent BBB, exercise scintigraphic results were only detailed in 4: 2 were normal, 1 had normal coronary arteries and no clinical problem other than intermittent BBB, and 1 had paroxysmal atria1 fibrillation but did not undergo coronary angiography. Scintigraphy was equivocal in 1 patient who also did not have coronary angiography. A single patient with a positive result had 80% left anterior descending stenosis. Significantly, in view of our results, no mention was made as to whether those patients with intermittent BBB had an episode of BBB during their exercise tests, suggesting that they did not.

The scant reports specifically dealing with exercise BBB are less comprehensive. Goodfriend et al4 de- scribed a man who had right BBB and left-axis deviation with exercise, but also with anxiety and amyl nitrite inhalation. He died sudldenly. Autopsy revealed 3-vessel CAD, but no lesions >>50%. There was intimal prolif- eration in the arteries of the atrioventricular node and His bundle and atrioventricular nodal fibrosis. On this basis, but without scintigraphy, the investigators sug- gested episodic ischemia as a cause for this otherwise apparently rate-related BBB.

A 30-year-old athlete with exercise BBB had also previously displayed intermittent left BBB that was felt to be rate-dependent, occurring at 78 beats/min with postural changes and minor activity and 85 beats/min at rest during right atria1 pacing.5 He had a normal an- giogram and only developed exercise BBB at 180 beats/min. The results were interpreted as suggesting autonomic influences on intraventricular conduction rather than ischemia a,s the cause of BBB.

Four patients with severe CAD had transient left posterior hemiblock, rather than complete BBB, with exercise.6 To ascertain if the hemiblock was due to new, transient ischemia or if’it was rate-related, the investi- gators used amyl nitrite or intravenous atropine in 2

patients to induce tachycardia above the rate at which hemiblock appeared during exercise. When it could not be induced, they concluded that it was due to ischemia.

The only reported case of exercise BBB with simul- taneous thallium perfusion imaging7 demonstrated anteroseptal ischemia in a man with proved CAD who had left BBB during exercise, thus invoking active ischemia as a cause. The patient later had an antero- septal infarct and permanent left BBB.

Such individual case reports and data make it diffi- cult to ascertain patterns of cause, significance, or clinical features in exercise BBB. Sandberg attempted to do so; he reported 9 patients, described from clinical data alone, without coronary angiography or scintig- raphy. He divided the cohort into 2 groups. One, a generally younger group of 3 patients, had left BBB only at a high level of exercise and were felt to have no car- diac disease. The remaining 6 were generally older, developed left or right exercise BBB at rather light work loads, and were regarded as abnormal because of a cardiac history such as angina. However, of the 3 ap- parently normal subjects, 1 had a history of chest dis- comfort with stress and another had a ventricular septal defect. Moreover, of the 6 patients regarded as having heart disease on history alone, only 4 had angina pec- toris and 2 had had rheumatic fever without subsequent heart disease. Thus, a classification of exercise BBB from these data is flawed.

Clinical and electrocardiographic character- istics: Our data do not suggest distinct age stratification in exercise BBB. A large proportion had a known, or highly likely, pretest diagnosis of CAD: 6 had had myocardial infarcts and 3 angina. The majority of pa- tients had an ECG abnormality before exercise. Only 2 had normal baseline electrocardiograms; 11 had a baseline IVCD or incomplete BBB. The type of exercise BBB was related to the baseline electrocardiogram. Thus, the 3 patients with incomplete right BBB had complete right BBB and the patient with incomplete left BBB had complete left BBB. Of the 7 patients with nonspecific IVCD, 5 had left BBB.

The heart rates at onset and offset of exercise BBB are interesting, particularly in view of the common conception that “rate-related” BBB is often benign. Of the 13 patients in whom BBB remitted after exercise, in 9 the onset and offset rates were within 8 beats/min. Of these 9,2 had reversible thallium perfusion defects, 4 CAD, 1 almost certainly coronary spasm, and 2 pri- mary myocardial disease. In 4 patients, offset rates were at least 28 beats/min lower than onset rates. Two of these had CAD (1 with old infarct and another with angiographic 3-vessel CAD), 1 had ventricular ar- rhythmias without other evidence of heart disease, and 1 was normal. The 3 patients in whom exercise BBB persisted all had CAD, documented by angiography in 2 and prior myocardial infarction in 1. Thus, rate-re- lated exercise BBB was associated with an appreciable incidence of CAD or myocardial abnormalities. Con- versely, in the 4 patients with discordant onset and offset rates, in whom ischemia rather than rate would otherwise be suspected, at least 1 was normal.

266 EXERCISE-INDUCED BUNDLE BRANCH BLOCK

Tachycardia-related BBB is regarded as “phase 3 block” g with prolonged recovery and increased duration of the action potential in part of the conducting system. This may be associated with hypopolarization, which slows conduction velocity. When electrical recovery is greatly prolonged, BBB may occur at relatively slow rates, explaining exercise BBB onset at rates in the 70s in 3 of our patients. Both prolonged recovery and hy- popolarization of conducting tissue can be caused by ischemia and myocardial disease. Tachycardia itself may induce or aggravate ischemia by diminishing dia- stolic coronary perfusion time or by exceeding the ability of damaged His-Purkinje fibers to conduct, leading to exercise BBB.

In all 13 cases of reversible exercise BBB, offset rate of BBB was equal to the onset rate or lower. This is also consistent with phase 3 block, where differences in these critical rates have been explained by prolonged duration of recovery of the affected bundle and “linking,” in which retrograde activation of the affected bundle from the normally activated ventricle perpetuates this pat- tern of ventricular activation even when heart rate is slowed to below the rate of BBB induction, over a variable rate range.g

Prognosis during follow-up study is also of interest, particularly in view of the Framingham study and other data1°-i2 dealing with the significance of newly acquired BBB. New left BBB was associated with a high inci- dence of antecedent cardiovascular abnormalities,1° particularly hypertension, cardiomegaly, and CAD. Subsequently, such patients had a high incidence of symptoms or complications of CAD and congestive heart failure and a mortality rate from cardiovascular disease and sudden death 5 to 10 times that of age- matched control subjects without left BBBlOJ1 in a 5- to lo-year follow-up, but with significant differences already apparent before 5 years. New right BBB was also associated with antecedent cardiovascular abnor- malities12; this included hypertension in as many as 60% of the cases. As with left BBB, new right BBB was later associated with a high incidence of symptomatic CAD, heart failure, and sudden death approximately 3 times that of control subjects.12 New right BBB was not an independent contributing factor to the increased risk of developing cardiovascular disease, but rather, a marker of increased mortality in view of its association with disorders such as hypertension.12 In men, new left BBB contributed independently to increased risk.lo

Our patients also had a high prevalence of pretest cardiovascular abnormalities. Of the 11 patients with

exercise left BBB, 5 (45%) had an antecedent problem: 3 hypertension, 1 diabetes, and 1 ventricular arrhyth- mias. Of the 5 patients with exercise right BBB, 3 had hypertension and 1 had type IV hyperlipoproteinemia. However, over a mean 28-month follow-up study, sub- sequent cardiovascular problems have been few. Neither of the 2 patients who died (at 7 and 32 months after exercise), both with prior infarcts, had further cardio- vascular complications before death from unrelated causes. Of the remaining 14 patients, 2 had uncompli- cated coronary bypass and 1 (Patient 16) had a nonfatal anterior infarct at 27 months. No other patient had a subsequent morbid cardiac event.

We conclude that exercise BBB is almost always as- sociated with cardiovascular disease, mostly CAD. It often displays a “rate-related” onset and offset and develops when tachycardia causes or aggravates ische- mia or exceeds the capacity of a damaged conduction system. It is not invariably associated with high mor- tality or morbidity.

Acknowledgment: We acknowledge Mary Ellen DeSantis and Linda Rzucidlo for secretarial assistance.

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