EDITORIAL
EDITORIAL:
From the Department of Emergency
Medicine, Albert Einstein College of
Medicine, Bronx, NY.
Reprints not available from the
author.
Address for correspondence:
E. John Gallagher, MD, Albert Einstein
College of Medicine, Department of
Emergency Medicine, 111 East 210th
Street, Bronx, NY 10467-2490;
718-920-7459, fax 718-798-6084;
E-mail jgallagh@montefiore.org.
Copyright © 2001 by the American
College of Emergency Physicians.
0196-0644/2001/$35.00 + 0
47/1/114761
doi:10.1067/mem.2001.114761
MAY 2001 37:5 ANNALS OF EMERGENCY MEDICINE
Which Patients With Suspected Myocardial
Ischemia and Left Bundle-Branch Block Should
Receive Thrombolytic Agents?
E. John Gallagher, MD See related article, p. 431.
[Gallagher EJ. Which patients with suspected myocardial
ischemia and left bundle-branch block should receive throm-
bolytic agents? Ann Emerg Med. May 2001;37:439-444.]
Timely administration of thrombolytic agents to patients
with ischemic ST-segment elevation decreases mortality in
acute myocardial infarction (AMI).1 Stratification of this
heterogeneous group of AMIs by ECG reveals a steep
risk/benefit gradient when expressed as the number of
patients needed to treat (NNT) or harm (NNH). As is evi-
dent from Figure 1, individuals with bundle-branch
block are a particularly important stratum of patients to
identify. This is true not only because they have a high
baseline mortality and receive the greatest incremental
improvement in survival when given thrombolytic
agents (NNT = 21; 95% CI, 12 to 72)1 but also because
we tend to undertreat them.2,3 The reluctance to admin-
ister thrombolytic agents to these patients can be
attributed, at least in part, to prevailing clinical confu-
sion driven by the ambiguity of the term bundle-branch
block (BBB).
In the Fibrinolytic Therapy Trialists’ (FTT) definitive
systematic review of 9 major randomized clinical trials of
thrombolytic agents versus placebo, no distinction was
made between left BBB (LBBB) and right BBB (RBBB).1
Rather, the 2 were merged into a single category, as
shown in Figure 1. Examination of each study entered
into the systematic review reveals that 2 trials excluded
patients with BBB (AIMS4 and USIM5), 1 did not code
BBB as a distinct ECG finding (ASSET),6 1 recorded LBBB
as a separate entity (GISSI),7 and the remaining 5 trials
simply reported undifferentiated BBB, presumably
aggregating LBBB with RBBB (ISAM,8 ISIS-2,9 ISIS-3,10
LATE,11 and EMERAS12).
Until such time as the more than 2,000 ECGs showing
BBB entered into the FTT systematic review1 can be ex-
humed from the archives of multiple study coordinating
4 3 9
EDITORIAL
centers, dusted off, and reclassified as left, right, or other,
or until further clarifying information on this subgroup is
forthcoming from additional sources, no explicit data are
available to determine whether the mortality decrement
associated with administration of thrombolytic agents to
patients with BBB and suspected AMI is distributed
equally or differentially between those patients with
RBBB versus those with LBBB.
In the absence of clear evidence, the logic of cardiac
conduction argues that suspected AMIs with LBBB rather
than RBBB are likely to receive the greatest therapeutic
benefit from thrombolysis. This is because normal con-
duction traverses the atrioventricular node and depolar-
izes the septum from left to right, thus activating the left
ventricle first. Standard 12-lead ECGs identify ischemia
or infarction most readily when it occurs in those areas of
the heart depolarized early. Hence, an RBBB, which does
not interfere with either the direction of septal depolar-
ization or the order of ventricular depolarization, will not
ordinarily obscure the ST-segment elevation of AMI be-
cause it does not greatly alter initial electrical forces.13,14
In contrast to RBBB, in the presence of an LBBB, con-
duction traverses the septum in the opposite direction
Figure 1.
Bars above the horizontal line demarcating benefit from harm
indicate the number of patients with suspected AMI needed to
treat (NNT) with thrombolytic agents (versus placebo) to save
one life, stratified by ECG findings. Note that the smaller the
NNT, the greater the incremental survival benefit. Bars below
the horizontal line indicate the number of patients with sus-
pected MI needed to harm (NNH), that is, the number who must
receive thrombolytic agents before one excess death occurs. Note
that those with ST-segment depression fare worse than those with
normal ECGs, although neither group benefits from thrombolysis.
Hi-low vertical lines display 95% CIs for the NNT and NNH.
Data were calculated from the FIT systematic review of indica-
tions for fibrinolytic therapy in suspected AMI.1
200
150
120
NNT
100
50
21 28 32
ST Normal
0
BBB Anterior Other Inferior
ST ST ST
50
NNH
100 72
ECG findings
150 144
4 4 0
(from right to left) and depolarizes the ventricles in the
reverse order through propagation of an electrical front
spreading radially across the left ventricle from the termi-
nation of the right bundle.15 This obscures early vectors
that ordinarily inscribe the characteristic ECG signature of
AMI, rendering it illegible in the vast majority of patients.
The American Heart Association (AHA) and American
College of Cardiology (ACC) appear to have followed
similar reasoning in formulating their recently updated
joint practice guideline.16 In the executive summary of
this extensive and well-referenced document, the Com-
mittee on Management of AMI states that “Symptoms
consistent with acute MI and left bundle branch block
(LBBB) should be managed like ST-segment elevation.”16
The authors go on to comment elsewhere in the guideline
that “Bundle-branch block (obscuring ST-segment analy-
sis) and history suggesting AMI [constitutes] a Class I
indication for thrombolysis.”16 Other than in the portion
of the document dedicated to indications for pacing in
AMI, RBBB is not mentioned further in the more than 200
pages of text. For the reasons noted above, this is presum-
ably because an RBBB tends not to obscure ST-segment
analysis.13-15 Thus, the recommendation of the
ACC/AHA appears to favor a logical strategy limiting
thrombolysis to those patients with suspected AMI and
LBBB, excluding those with RBBB unless they also have
evidence of ischemic ST-segment elevation.
Consistent with the notion that identification of AMI
in the context of an LBBB is both important and difficult,
more than 50 ECG signs have been proposed over the past
half century for the detection of ischemia in LBBB.17 Of
these, 2 of the 3 criteria recently proposed by Sgarbossa et
al18 appear to have sufficiently powerful likelihood ratios
to be helpful at the bedside: (1) ST-segment elevation of 1
mm or more in the same direction as the QRS complex
and (2) ST-segment depression of 1 mm or more in leads
V1, V2, or V3. For practical use, these criteria can be
remembered simply as directional concordance of the ST
segment with the QRS complex immediately preceding it.
Under ordinary circumstances, such concordance is
unusual because the primary depolarization abnormality
of LBBB is followed by a secondary abnormality in repo-
larization. Thus, in LBBB the ST–T-wave complex will
normally move in a direction opposite (discordant) to
that of the QRS deflection. When this fails to occur, the
resulting QRS-ST concordance strongly suggests acute
coronary occlusion. More specifically, concordance of
elevation suggests AMI in almost any lead; concordance
of depression is most indicative of AMI when seen in the
right precordial leads V1, V2, or V3.18
ANNALS OF EMERGENCY MEDICINE 37:5 MAY 2001
EDITORIAL
Unfortunately, as Kontos et al19 convincingly demon-
strate in this month’s issue of Annals, the criteria of
Sgarbossa et al18 are too insensitive to be used as a screen-
ing (rule out) test to determine which patients with an
LBBB do not have an MI. Indeed, if one combines the
prospective data gathered by Kontos et al with recent ear-
lier retrospective work targeted at the same end point,20
the 2 Sgarbossa criteria were found in only 3% (95% CI,
2% to 6%) of 372 patients with LBBB and suspected
ischemia. Among the subset of 49 patients with LBBB and
confirmed AMI, at least one of the 2 criteria was present in
only 20% of patients (95% CI, 10% to 34%). The
Sgarbossa criteria are, however, highly specific (96%;
95% CI, 94% to 98%) and can be used reliably as a confir-
matory test to rule in AMI in patients with LBBB.19,20
A better sense of the clinical utility of the Sgarbossa crite-
ria18 can be obtained by converting the traditional test
properties of sensitivity and specificity into likelihood ratios
(LRs).21 Use of positive and negative predictive values is
misleading because they fluctuate directly as a function of
the prevalence of the target disorder in the population to
which the criteria are applied.22 If one defines the presence
of either concordant criterion as a positive test result and the
absence of both criteria as a negative test result, the positive
LR is 22 (95% CI, 7 to 72) and the negative LR is 0.8 (95%
CI, 0.7 to 0.9). A positive LR reflects the odds that a patient
with a positive test result has the target disorder, in this case
AMI, as opposed to the odds that a patient with the same
positive test result does not have AMI:
Positive LR = Sensitivity/(1 – Specificity).
In contrast, a negative LR reflects the odds that a patient
with a negative test result has the target disorder, AMI, as
opposed to the odds that a patient with the same negative
test result does not have an AMI:
Negative LR = (1 – Sensitivity)/Specificity.
The degree to which the LR of a test deviates from one
(positive LR >1; negative LR <1) is indicative of the power
of that test to revise disease probability. Thus, the effect of
a negative test result (ie, absence of both criteria) will re-
duce the posttest odds of AMI only marginally by a factor
of 0.8. Therefore, lack of concordance of ST segments with
the QRS complex in a patient with LBBB and suspected
ischemia is of no help diagnostically and should not be
used in clinical decisionmaking to rule out AMI. In con-
trast, the presence of ST-segment and QRS concordance
increases the odds of AMI in the setting of LBBB by about
22-fold, essentially confirming the diagnosis anytime
either of the concordant Sgarbossa criteria are seen.
Kontos et al19 use the low sensitivity (poor negative
LR) of the Sgarbossa criteria to support their argument
MAY 2001 37:5 ANNALS OF EMERGENCY MEDICINE
that too few people with AMI would be treated if these cri-
teria were used to identify thrombolytic candidates with
LBBB. These authors also point out that the low prevalence
of AMI among patients with LBBB would unnecessarily
expose too many people to the risks of thrombolytic
agents in return for insufficient benefit. Although their
former position seems squarely evidence based, the latter
is at odds with the ACC/AHA’s summary recommenda-
tion to treat all patients with LBBB with suspected AMI16
and therefore warrants closer examination.
One means of explicitly weighing the quantitative im-
plications of competing therapeutic recommendations is
through use of decision analysis. Shlipak et al23 per-
formed such an analysis recently, concluding that treat-
ment of all patients with LBBB and suspected AMI would
result in about 10 more lives saved (without the compli-
cation of stroke, stroke-free) per 1,000 patients than
either use of the Sgarbossa ECG criteria18 to select
patients for thrombolysis or a strategy of declaring all
patients with LBBB ineligible for thrombolytic agents.23
However, this analysis was based on a prevalence of AMI
in LBBB that was nearly twice that found by Kontos et al19
and Li et al,20 who reported an identical prevalence of
13% (95% CI for combined cohort, 10% to 17%).
Shlipak et al23 also did not have information on the age
of the LBBB to incorporate into his decision analysis,
which both Li et al20 and Kontos et al19 have recently
shown may have some predictive utility in identifying
patients at particularly high risk for AMI. Stratification by
age of the LBBB, again combining data from Li et al and
Kontos et al (provided by the lead authors of each article
on request), allows calculation of interval likelihood
ratios for the odds of AMI among patients with new (LR,
1.7; 95% CI, 1.1 to 2.7), indeterminate (LR, 1.1; 95% CI,
0.8 to 1.5), and old LBBB (LR, 0.5; 95% CI, 0.3 to 0.8).
Although a slight gradient is evident, the LR associated
with the distinction between old versus new or indeter-
minate LBBB appears to be the only LR that might be clini-
cally useful. However, even this is a relatively weak test,
indicating that the presence of an LBBB known to be old
reduces the odds of AMI by only about one half.
Further consolidation of these 3 categories of LBBB
into 2 groups (new/indeterminate/presumably new ver-
sus known to be old) is consistent with the ACC/AHA’s
practice guideline, in which they state that “Thrombolytic
therapy is highly effective in patients with ST elevation or
presumably new LBBB (which obscures the electrocar-
diographic diagnosis of MI).”16 From this grouping, it
should then be possible to develop a decision analysis
comparing performance of the combined criteria of either
4 4 1
EDITORIAL
concordant Sgarbossa ECG criteria18 OR a new/indeter-
minate LBBB as a positive test result indicating need for
thrombolysis with the simpler strategy of administering
thrombolysis to all patients with LBBB and suspected
AMI. Consistent with this model, a negative test result
would then be defined by the presence of BOTH
Sgarbossa concordant criteria AND an LBBB known to be
old. Given the high positive LR of the concordant
Sgarbossa ECG criteria, providing thrombolytic agents to
no patients with LBBB and suspected AMI is not a clini-
cally sensible strategy and will not be included as a third
branch in the decision tree.
The range of probabilities used for sensitivity analyses
at each decision node is based on the 95% CIs surrounding
the point estimates, as shown in Table 1.1,19,20,23,24 The
prevalence of AMI in patients with LBBB and the test prop-
erties of the concordant Sgarbossa ECG criteria are drawn
from the combined data of Kontos et al19 and Li et al,20 as
presented previously. The frequency of stroke and death
among patients with AMI and LBBB who receive or do not
receive thrombolytic agents is taken from the FTT defini-
tive systematic review.1 Mortality among untreated patients
without MI is derived from data on outcomes of patients
hospitalized for suspected ischemia who neither had an
MI nor received thrombolytic agents.24 By definition,
among patients with MI, the sensitivity of the combined
criteria will equal the probability of receiving thromboly-
sis according to the algorithm displayed in Figure 2.
Similarly, in patients without MI, the specificity of the
Table 1.
Probability estimates for decision analysis.
Probability in Patients
With LBBB Estimate (%)
AMI19,20 13
Death: (–) thrombolysis, (–) AMI23,24 2†
Death: (–) thrombolysis, (+) AMI1 23.6
Death: (+) thrombolysis, (–) AMI23 2.2
Death: (+) thrombolysis, (+) AMI1 18.7
Stroke: (+) thrombolysis1 2.1
Stroke: (–) thrombolysis1 1.1
Sensitivity of combined criteria19,20 82
Specificity of combined criteria19,20 38
*
Range for sensitivity analyses are based on 95% CIs of estimate.
†
Range23 and estimate24 are based on different sources. Therefore, 95% CIs were not used for
sensitivity analysis of patients who neither had AMI nor received thrombolytic agents but were
hospitalized for suspected myocardial ischemia.
4 4 2
combined criteria will equal the probability of not receiv-
ing thrombolytic agents according to the same algorithm.
Comparison of these combined criteria with a strategy
of thrombolysis for all patients with LBBB and suspected
ischemia according to a standard decision analysis
(Figure 2) reveals that the outcomes of the 2 strategies are
remarkably similar (Table 2). This appears to be true with
respect to mortality, as well as stroke-free survival. For
quality-of-life estimates, dividing those patients who had
a stroke into those with major and minor disability1 and
assigning to major stroke a weight equivalent to death
does not materially alter the conclusion that an algorithm
incorporating the concordant Sgarbossa criteria com-
bined with the age of the LBBB performs no better than
the much simpler strategy of thrombolysis for all sus-
pected AMIs in patients with LBBB.
Why might this be? Kontos et al19 and Li et al 20 have
already shown that the Sgarbossa criteria perform
poorly as screening tests because most patients with
LBBB and AMI do not have either concordant ST-seg-
ment elevation or depression. With respect to the age of
the LBBB, one plausible reason for finding such poor
discrimination, as was suggested by the marginal inter-
val LRs estimated above, might be the decidedly differ-
ent clinical implications of an LBBB not previously
noted (and therefore characterized as “presumably
new”) versus one that develops acutely on serial ECGs in
real time. Most clinicians would agree that the latter, if
not rate related or toxic-metabolic, is strong evidence of
ischemia. In contrast, an LBBB that appears to be new
rather than acute could, in fact, be quite old, if only
because the age of the LBBB is arbitrarily defined by
whether it was previously noted in the medical record.
Range for Table 2.
Sensitivity
Analysis* (%)
Outcome of decision analysis comparing 2 strategies for adminis-
tration of thrombolytic agents to 1,000 patients with LBBB and
suspected AMI.
10–17
1–3†
21.0–26.2
0.9–3.1 Application of Algorithm* Thrombolysis
16.3–21.1 Outcome for All (per 1,000) for All (per 1,000)
1.3–3.2
0.5–1.9 Mortality 43–44 43–44
68–91 Stroke-free survival 935–944 935–944
32–43 *The thrombolysis algorithm shown in Figure 2 is defined as thrombolytic agents administered
to any patient with either of the 2 concordant Sgarbossa criteria18 or an LBBB of “new/indeter-
minate” age, that is, not known to be old. Thrombolysis was withheld from any patient with
neither concordant Sgarbossa criteria nor an LBBB known to be “old,” that is, noted before cur-
rent presentation.
ANNALS OF EMERGENCY MEDICINE 37:5 MAY 2001
EDITORIAL

Thus, the poor performance of the age of the LBBB in a
decision analysis, even when combined with the con-
cordant Sgarbossa criteria,18 might simply reflect the
inadequacy of our operational definitions of new/inde-
terminate versus old LBBB and the confounding of these
designations by random circumstance (eg, when an
individual last happened to have an ECG at that particu-
lar institution).
Kontos et al19 are entirely correct in concluding that
the Sgarbossa criteria “identify only a small minority of
patients” and that administering thrombolytic agents to
all patients with LBBB and suspected ischemia “would
result in treatment of a significant number of patients
without AMI.” Unfortunately, quantitative interpretation
of a large body of evidence,1,19,20,23,24 with the aid of
decision analysis,18 suggests that combining the

Figure 2.
Decision analysis comparing 2 strategies for administering thrombolytic agents to patients with LBBB and suspected AMI: application of
thrombolytic algorithm (see text for details) versus thrombolysis for all suspected AMIs with LBBB. Probabilities and ranges for sensitivity
analyses at each decision node are listed in Table 1. Outcomes are displayed in Table 2.

LBBB with
suspected AMI

Thrombolysis Thrombolysis
algorithm for all

(+) MI (–) MI (–) MI

Alive, Alive, Death

no stroke stroke

(+) MI

Alive, Alive, Death

(+) Algorithm => no stroke stroke
thrombolysis

Alive, Alive, Death

no stroke stroke

(–) Algorithm =>

no thrombolysis

Alive, Alive, Death

no stroke stroke

(+) Algorithm =>

thrombolysis

Alive, Alive, Death

no stroke stroke

(–) Algorithm =>

no thrombolysis

Alive, Alive, Death

no stroke stroke

MAY 2001 37:5 ANNALS OF EMERGENCY MEDICINE 4 4 3

EDITORIAL

Sgarbossa criteria with the presumed age of the LBBB to 17. American College of Emergency Physicians. Clinical policy: critical issues in the evaluation
and management of adult patients presenting with suspected acute myocardial infarction or
create an algorithm confers no improved mortality or unstable angina. Ann Emerg Med. 2000;35:521-544.
quality-of-life benefit when compared with administra- 18. Sgarbossa EB, Pinski SL, Barbagelata A, et al. Electrocardiographic diagnosis of evolving
tion of thrombolytic agents to all suspected AMIs in acute myocardial infarction in the presence of left bundle-branch block. GUSTO-I (Global
patients with LBBB. Although this may seem both unsatis- Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries)
Investigators. N Engl J Med. 1996;334:481-487.
factory and counterintuitive, it does appear to be evi-
19. Kontos MC, McQueen RH, Jesse RL, et al. Can myocardial infarction be rapidly identified in
dence based. Until such time as contravening data emergency department patients who have left bundle-block branch block. Ann Emerg Med.
become available, the best answer to the question of 2001;37:431-438.
which patients with suspected AMI and L-BBB should 20. Li SF, Walden PL, Marcilla O, et al. Electrocardiographic diagnosis of myocardial infarction
receive thrombolysis is also the simplest: “All of them.” in patients with left bundle branch block. Ann Emerg Med. 2000;36:561-565.
21. Gallagher EJ. Application of likelihood ratios to clinical decision rules: defining the limits of
clinical expertise. Ann Emerg Med. 1999;34:664-667.
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4 4 4 ANNALS OF EMERGENCY MEDICINE 37:5 MAY 2001