Diagnostic accuracy of exercise electrocardiogram in patients with left anterior hemiblock

Background: Left anterior hemiblock (LAHB) is the most frequent conduction abnormality, but its impact on the diagnostic accuracy of the exercise ECG has not been studied. The aim of our study was to determine the diagnostic accuracy of ST depression for predicting ischaemia in the presence of LAHB. Patients: Consecutive patients with known or suspected coronary heart disease undergoing exercise ECG and 99mTc-sestamibi single photon emission computed tomography (SPECT) were included in the analysis. Patients with left bundle branch block, with changes in QRS morphology related to myocardial infarction, and patients who had undergone pharmacological stress testing were excluded. Results: Of 1532 patients assessed, 567 patients qualified for the analysis. In 69 patients with LAHB, ECG stress testing had lower sensitivity (38% vs 86%) and lower negative predictive value (82% vs 92%) than in patients with normal baseline ECG. The reduction of sensitivity appeared to be similar in patients with isolated LAHB (n = 43), in patients with right bundle branch block (n = 39), and with bifascicular block (n = 26). In contrast, the positive predictive value of the test was excellent. Conclusion: The diagnostic accuracy of the exercise ECG for prediction of ischaemia is reduced in patients with LAHB.


Patients
Consecutive patients with known or suspected coronary artery disease who underwent exercise electrocardiogram and 99mTc-sestamibi single photon emission com-puted tomography (SPECT) were included in a retrospective analysis.Patients with left bundle branch block, left posterior hemiblock, non-specific intraventricular conduction disturbances, QRS alterations post myocar-dial infarction or with inadequate-quality exercise ECG tracings were excluded, as were patients who had undergone pharmacological stress testing with dipyridamole.
The criteria for LAHB were a leftward QRS axis of -30° to -90°, rS pattern in leads II, III, aVF and a deep Q wave in aVL, with normal QRS duration [8].Criteria for LAHB combined with RBBB additionally included the presence of a typical rSR' pattern in V1 with a QRS width of 120 msec or more.

Exercise ECG
All patients underwent a symptom-limited upright bicycle ergometry test.Treatment with beta-blocker or digoxin was stopped four days before the test.Blood pressure was measured every two minutes using the Riva-Rocci method.Three ECG leads were monitored continuously.A 12-lead ECG was recorded at rest and every minute until the end of the recovery phase.All ECG printed at a paperspeed of 25 and 50 mm/sec were analysed manually.An ischaemic response was defined as 00.1 mV horizontal or downsloping ST segment depression compared with baseline in at least two adjacent leads in V4-V6, measured 80 ms from the J point at heart rate <130 bpm, and 60ms from the J point at heart rate 0130 bpm.

SPECT imaging
SPECT imagings at rest and post-exercise (symptom-limited) were performed at least 48 hours apart.Treatment with beta-blocker was stopped four days before the test.Approximately one minute before termination of the exercise stress test an intravenous dose of 99m technetium methoxy isobutyl isonitrile sestamibi was given.A dose of 1 GigaBq was given to patients weighing 75 kg or over and of 800 MBq to patients weighing less than 75 kg.Stress images were acquired 30 minutes after termination of the test using a PRISM 3000 gammarecorder (Picker).For resting studies the same isotope was injected 24 hours after the stress study, and resting images were recorded 60 minutes after injection.For each study six oblique (short axis) slices from the apex to the base and three sagittal (vertical long axis) slices from the septum to the lateral wall were defined.Each of the six short axis slices was divided into eight equal segments.The scan was interpreted semiquantitatively by visual analysis assisted by circumferential profile analysis.Myocardial perfusion was assessed by measuring the area between the lower limit of normal values (±2 SD) and the actual circumferential profile of the patient on rest and stress images.Stress and rest tomographic views were reviewed side by side by an experienced observer who was unaware of stress-induced ECG abnormalities or angiographic data.A reversible perfusion defect was defined as a perfusion defect on stress images which partially or completely resolved at rest in two or more contiguous segments or slices.A fixed perfusion defect was defined as a perfusion defect on stress images in two or more contiguous segments or slices which persisted on rest images.

Statistical analysis
Continuous data were expressed as mean values ± SD.Comparisons between categorical variables were analysed using the chi-square test.Quantitative variables were compared using analysis of variance (ANOVA).Differences were considered significant at a p value of <0.05, whereas statistical significance levels were adapted in line with Bonferroni's correction in between-group comparisons of continuous variables.

Patient characteristics and ECG
Of 1532 consecutive patients screened, 965 were excluded.The reasons for their exclusion are shown in table 1.
The study population consisted of 567 patients, including 69 with LAHB, 39 with RBBB, and 459 without baseline ECG abnormalities.The clinical characteristics of the patients are detailed in table 2.

Diagnostic accuracy of exercise ECG
The sensitivity, specificity, and positive and negative predictive values based on the presence or absence of LAHB and RBBB on baseline ECG are given in table 3.
The sensitivity of the exercise ECG was lower in patients with LAHB and RBBB than in controls, and specificity was higher in patients with LAHB than in control patients and patients with  RBBB.Figures 2 and 3 illustrate sensitivity and specificity according to increasing ST-segment depression cut-off values.
In an additional analysis the diagnostic accuracy of ischaemia-induced ST changes in patients with isolated LAHB (n = 43), LAHB and RBBB (n = 26), or in all patients with LAHB (n = 69), were compared (tab.3 and fig.4).The test's sensitivity was not significantly lower in the presence of bifascicular block than in the presence of isolated LAHB, whereas the test's specificity appeared to be lower in patients with bifascicular block when compared to patients with isolated LAHB.

QRS-configuration subgroup analysis in patients with LAHB
The patients with LAHB included 47 with rS configuration (r<S) and 22 with Rs configuration (R>s) in leads V4-V6.The sensitivity of the test was 20% in patients with rS (r<S), but 67% in patients with Rs (R>s) configuration.

Discussion
The principal results show that the diagnostic accuracy of ECG stress testing is decreased in patients with LAHB, in relation with a marked reduction in test sensitivity.Accordingly, the absence of ST-segment depression in patients with LAHB has a lower negative predictive value than in patients with normal baseline ECG.The reduction in test sensitivity appeared to be similar in pa-tients with isolated LAHB compared with patients with RBBB or with bifascicular block (LAHB and RBBB).In contrast to its low sensitivity and negative predictive value, the test has excellent positive predictive value.
LAHB occurs when an impulse spreads first through the left posterior fascicle, causing a delay in activation of the anterior and lateral walls of the left ventricle.In patients with LAHB, the amplitude of positive QRS deflection in V4-V6 may be markedly decreased, as illustrated in our series: the positive vector in V5-6 (r wave) was lower than the negative vector (S wave) in 58% of the patients.
Stress-induced ST segment depression is caused largely by reduction of perfusion to the sub-endocardium, the zone most vulnerable to ischaemia, and is usually manifest during exercise ECG in leads V4-V6.In these leads R waves are dominant, ischaemia-induced variations of the ST  A B segment being discordant.While the depth of ST depression is chiefly determined by the severity of ischaemia and the extent of ischaemic area, it is also influenced by the amplitude of the R wave.Accordingly, it can be assumed that ST-segment response to ischaemia is decreased due to the small positive vectors in the lateral precordial leads which are typical of LAHB.
In agreement with this assumption, a subanalysis suggests that the sensitivity of the test may be at least partially preserved in patients with LAHB and larger positive vectors in the lateral precordial leads, defined by R>s in V5-V6.
In our study the specificity of ECG exercise stress testing in the control group was low compared to the majority of previous studies [9][10][11].This may have been due to referral bias: on the one hand, patients with negative exercise stress testing may have been dismissed without further clinical investigations such as SPECT imaging, thus reducing the overall number of true and false negative results.This may explain the fact that the number of positive test results was considerably higher than the number of negative results.On the other hand, patients with acute coronary syndrome or very high pre-test probability for coronary artery disease were investigated by coronary angiography without previous exercise testing.However, since this patient selection procedure is recommended in most clinical guidelines, the resulting population investigated in our study can be considered typical of a cardiological clinical environment.

Limitations
We used SPECT imaging as reference for the presence or absence of ischaemia.This technique has known limitations in the evaluation of patients with left main stenoses and severe threevessel disease, but diagnostic accuracy was reported to be excellent even in patients with RBBB and LAHB [12].

Clinical implications
Our findings have important clinical implications.In view of the low negative predictive value of stress induced ST-segment depression, other functional tests should be preferred to evaluate coronary perfusion in patients with LAHB.The sensitivity of the exercise ECG is particularly low in patients with an rS pattern in V5-6.However, in the small group of patients with LAHB and large positive vectors in lateral precordial leads (R>s in V5-6), sensitivity attains higher values than in patients with a very small positive vector in these leads.Finally, in the rather uncommon eventuality of exercise-induced ST depression in the setting of LAHB (with or without RBBB), the specificity of the finding as a marker of ischaemia is very high.
In conclusion, exercise ECG has a reduced sensitivity in detecting myocardial ischaemia in patients with LAHB, and other functional tests should be considered.

Correspondence: Etienne Delacrétaz, MD Swiss Cardiovascular Center Bern
University Hospital CH-3010 Bern Switzerland E-Mail: etienne.delacretaz@insel.chBox plots showing sensitivity and specificity values of exercise ECG in the subgroup analysis comparing patients with isolated left anterior hemiblock (LAHB), LAHB associated with right bundle branch block (RBBB), and isolated RBBB.See text for detailed explanation.

Figure 2
Figure 2Sensitivity of exercise ECG to detect myocardial ischaemia according to different ST depression cut-off values in the three groups.LAHB, left anterior hemiblock, RBBB, right bundle branch block.The numbers of true positive results are indicated.See text for detailed explanation.

Figure 3
Figure 3 Specificity of exercise ECG for the detection of myocardial ischaemia according to different ST depression cut-off values in the three groups.LAHB, left anterior hemiblock, RBBB, right bundle branch block.The numbers of false positive results are indicated.See text for detailed explanation.

Table 2
Clinical characteristics.