Abstract
Background
Electrophysiological study (EPS) is indicated in patients with syncope and bundle branch block (BBB). Data about predictors of positive EPS in these patients is scarce.
Objective
To assess clinical and electrocardiographic (ECG) predictors of positive EPS in patients with syncope and BBB.
Methods
Observational single‐center study that included all consecutive patients with syncope and BBB that underwent EPS from January 2011 to June 2017. Results of EPS were considered positive according to current ESC syncope guidelines.
Results
During study period, 271 patients were included (64.9% male, age: 73.9 ± 12.2 years, number of syncopal episodes: 2.4 ± 2.5, LVEF: 56.1 ± 9.9%). Type of BBB: RBBB + LAFB/LPFB in 39.8%, isolated LBBB in 38.7% and isolated RBBB in 18.5% of the patients. Duration of QRS and PR interval were 141.9 ± 16.7 and 182.8 ± 52.2 milliseconds. EPS was positive in 41.7% of the patients. In multivariate analysis, conduction disturbance pattern and long PR interval (OR 8.6; 2.9‐25; P < 0.0001) were predictors of positive EPS. Conduction disturbance patterns related with positive EPS were: BBB different than isolated RBBB (OR 15.2; 2.2‐23.4; P = 0.005), LBBB or RBBB+long PR + left fascicular block (OR 4.5; 1.06‐20.01; P < 0.042), and RBBB+left fascicular block compared with LBBB (OR 4.8; 1.2‐16.7; P = 0.025). Clinical factors and syncope characteristics were not related with EPS result.
Conclusions
Diagnostic yield of EPS in patients with syncope and BBB is moderate (41%). Type of conduction disturbance pattern and PR interval are associated with the electrophysiological (EP) test result. Patients with LBBB or bifascicular block have the highest rate of positive EP test. Long PR interval increases the proportion of positive EPS in all conduction disturbance patterns.
1. INTRODUCTION
Patients admitted for syncope have higher risk of mortality and cardiovascular events.1 However, prognosis is completely different depending on the etiology of syncope.2 Whereas patients with neuro‐mediated syncope have similar prognosis as general population, patients with cardiac syncope have a higher mortality. In this sense, is already known that patients with syncope, bundle branch block (BBB) and prolonged His‐ventricular (HV) interval is at risk of developing high degree atrioventricular (AV) block.3, 4 Thus, European Society of Cardiology (ESC) Syncope Guidelines5 recommend to perform an electrophysiological study (EPS) in patients with syncope and BBB, regardless the electrocardiographic (ECG) pattern of conduction disturbance. Permanent pacing is recommended in case of prolonged HV interval or induction of AV block by pacing or by pharmacological stress.6 However, EPS has low sensitivity and the absence of abnormal findings does not exclude the development of AV block during follow‐up.1, 7, 8, 9 Therefore, the diagnostic yield of EPS in patients with syncope, BBB and suspected bradyarrhythmia is variable and it might be because of differences in clinical presentation and ECG conduction disorders. There are very few data on predictors of positivity of EPS among patients with syncope and BBB. Only first‐degree AV block10 is suggested as marker of higher positivity EPS rate. The aim of this study is to identify clinical and ECG predictors of positive EPS for bradyarrhythmia. By identifying these predictors, the management of the patients with syncope and BBB could be changed to early pacemaker implantation in patients in whom the positivity rate of EPS is very high or to replace EPS for other tools with higher diagnostic yield (ie, insertable loop recorder, [ILR]) in groups in whom the EPS diagnostic yield is presumed to be very low.
2. METHODS
This is a single‐center observational study that includes all consecutive patients undergoing EPS for syncope and BBB at Vall d'Hebrón University Hospital between January 2009 and June 2017. Patients with established indication for pacing (3rd degree, Mobitz II or advanced 2nd degree AV block) or with severely depressed left ventricular ejection fraction (LVEF ≤35%) were excluded. Clinical data including age, sex, cardiovascular risk factors, use of bradyarrhythmic drugs, and clinical characteristics of syncopal episodes were collected from clinical history. Total number of syncope episodes, number of syncopes in the last 6 months and in the previous month, as well as the presence of prodromal symptoms and trauma injury reports were gathered. Left ventricle measurements and LVEF were obtained from echocardiogram data. The following data from 12‐lead ECG was collected: sinusal or atrial fibrillation rhythm, PR interval, QRS duration, right bundle branch block (RBBB), left bundle branch block (LBBB), left posterior fascicular block (LPFB), left anterior fascicular block (LAFB). For EPS, two femoral venous access were gained. Two tetrapolar catheters (Supreme St Paul, Minesotta, US) were used for basic measurements and ventricular stimulation in case of structural heart disease. Sinus node recovery time was obtained after 30 seconds of atrial pacing at 600 and 500 milliseconds and the highest value was corrected by basal heart rate. In case of HV interval inferior to 70 milliseconds, class IC drug (Procainamide 10 mg/kg or Flecainide 2 mg/kg, i.v. 10 minutes infusion) was administered. EPS was considered positive according to current ESC guidelines (REF) in the following cases: corrected sinus node recovery time > 525 milliseconds, baseline HV interval ≥ 70 milliseconds or ≥ 100 milliseconds after IC drug administration, second or third degree infra‐His block during incremental atrial pacing or after IC drug administration. Transient mechanical AV block in LBBB patients due to the placement of the diagnostic catheter in the His bundle has not been considered as positive EPS. In these patients, EPS parameters have been evaluated after AV conduction recovery.
2.1. Statistical analyses
Continuous variables are expressed as mean ± SD and range. Categorical variables are represented by frequencies and percentages. A descriptive analysis of clinical, ECG, and procedure‐related variables was performed. For univariate analysis, χ 2 or Fisher's exact test was used for dichotomous categorical variables (with calculation of 95% confidence interval [CI]), anova test for non‐dichotomous categorical variables, and Student's t test for continuous variables. Two‐tailed values of P ≤ 0.05 were considered statistically significant. Variables with a P‐value≤0.1 in the univariate analysis were considered for a logistic regression multivariate analysis. Analyses were performed with SPSS software Mac OS version 20.0 (IBM SPSS Statistics, Chicago, Illinois). The ethics review board of our institution approved the study.
3. RESULTS
3.1. Study population
A total of 271 patients (64.9% male, age 73.95 ± 12.2 years) were analyzed. Comorbidities, syncope characteristics, echocardiogram data, and ECG abnormalities are listed in Table 1. Previous coronary artery disease was present in 59 (21.8%) patients and mean LVEF was 56.1 ± 9.9%. Among the study population, the mean number of syncopal episodes was 2.45 ± 2.51. The syncopal episode occurred without prodromal symptoms in 160 (59%) patients and was associated with trauma injury in 114 (42.1%) patients. In our study, most of the patients (227; 83.8%) were in sinus rhythm. First‐degree AV block was present in 68 (25.1%) and mean PR interval was 182.8 ± 52.2 milliseconds. QRS duration was 141.9 ± 16.7 milliseconds and the distribution of ECG pattern was: RBBB + LAFB/LPFB in 108 (39.8%) patients, isolated LBBB in 105 (38.7) patients, and isolated RBBB in 50 (18.5) patients.
Table 1.
Baseline characteristics and electrophysiological study results
| Baseline characteristics | |
|---|---|
| Parameter | Value |
| Patient characteristics | |
| Age (years) | 74 ± 12 (17‐93) |
| Male sex | 176 (64.9) |
| Hypertension | 213 (78.6) |
| Diabetes | 88 (32.5) |
| Dyslipidemia | 159 (58.7) |
| Coronary artery disease | 59 (21.8%) |
| Syncope characteristics | |
| Syncope episodes | 2.45 ± 2.44 (1‐20) |
| Number of syncopes last 6 months | 1.56 ± 1.44 (1‐10) |
| Syncope‐EPS time (days) | 101.8 ± 41.31 |
| Absence of prodromal symptoms | 160 (59.0) |
| Trauma injury | 114 (42.1) |
| ECG characteristics | |
| Sinus rhythm | 227 (83.8) |
| First‐degree AV block | 68 (25.1) |
| PR interval duration (ms) | 182.8 ± 52.2 |
| Left bundle branch block | 105 (38.7) |
| First‐degree AV block | 26 (9.5) |
| Right bundle branch block | 158 (58.3) |
| Associated left anterior or posterior fascicular block | 108 (39.8) |
| First‐degree AV block | 42 (15.4) |
| QRS duration (ms) | 141.9 ± 16.7 |
| Echocardiogram characteristics | |
| Left ventricular ejection fraction (LVEF) (%) | 56.1 ± 9.9 (38‐67) |
| Left ventricle end‐diastolic diameter (mm) | 48.5 ± 7.5 |
| Left ventricle end‐systolic diameter (mm) | 32.1 ± 8.2 |
| Septum thickness (mm) | 12.8 ± 2.62 |
| Posterior wall thickness (mm) | 11.1 ± 2.1 |
| Moderate‐severe valvular heart disease | 35 (12.9) |
| EPS results | |
| Parameter | Value |
| Positive EPS | 113 (41.7) |
| CSNRT (ms) | 122.3 ± 99.3 |
| CSNRT>525 (ms) | 1 (0.4%) |
| Basal HV interval (ms) | 60.7 ± 14.8 (33‐123) |
| HV ≥ 70 (ms) | 81 (31.4) |
| Basal infrahisian block | 15 (5.5) |
| HV interval after IC drugs challenge (ms) | 69.8 ± 14.5 |
| HV ≥ 100 (ms) | 7 (2.5) |
| Infrahisian block after IC drugs challenge | 10 (3.7) |
| Induction of sustained monomorphic ventricular tachycardia | 2 (0.7) |
AV: atrioventricular; CSNRT, corrected sinus node recovery time; EPS: electrophysiological study, ECG: electrocardiogram; HV, His‐ventricular.
Data are presented as: n (%) or mean ± SD (range).
3.2. EPS results
Overall, EPS was positive in 113 (41.7%) patients. Mean HV interval at baseline was 60.7 ± 14.8 milliseconds, while HV interval after IC drug administration was 69.8 ± 14.5 milliseconds. At baseline, HV interval ≥ 70 milliseconds was present in 81 (31.4%) patients and 15 (5.5%) patients developed infra‐His block during incremental atrial pacing. Among those patients with negative EPS at baseline (174 patients, 64.2%%), administration of IC drug led to diagnostic result in 17 (9.7%) patients. Details about EPS results are listed in Table 1. All patients with positive EPS underwent pacemaker implantation with a significant lower syncope recurrence rate of 8.1% vs 27.1% in patients with negative EPS (hazard ratio 3.05; CI 95% 1.3‐7.8; P < 0.001) after follow‐up of 25.8 ± 6.3 months. In three patients, abnormal sinus node recovery time (one patient) and well‐tolerated and self‐sustained ventricular tachycardia (two patients) was induced. In all these patients, HV interval was also abnormal (>70 milliseconds) and a pacemaker was implanted.
3.3. Univariate and multivariate analysis of predictors of positive EPS
Univariate predictors of positive EPS are listed in Table 2. In the present study, we did not observe a statistically significant association between age, cardiovascular risk factors, coronary artery disease or number or characteristics of syncope and advanced His‐Purkinje disturbances in the EPS. The only predictors of positive EPS for bradyarrhythmia were higher left ventricle diameter, lower LVEF, longer PR interval, wider QRS, and type of BBB. In Figure 1, proportion of positive EPS in relation to absence or presence of different conduction disturbance patterns and long PR interval is shown. On multivariate analysis (Table 3), the only predictor of positive EPS was the conduction disturbance pattern in the ECG and long PR interval (OR 8.65; 95% CI 2.9 ‐25.1; P < 0.0001). Patients with BBB different than isolated RBBB had a 15‐fold increase in their risk of positive EPS when compared with patients with isolated RBBB (OR 15.2; 95% CI 2.2‐23.4; P = 0.005). In the same line, patients with LBBB or RBBB plus long PR and left fascicular block had 4‐fold increase of risk of positive EPS (OR 4.54; 1.06‐20.01; P < 0.042). Finally, patients with RBBB and left fascicular block compared with patients with LBBB had almost 5‐fold increase of risk of positive EPS (OR 4.8; 1.2‐16.7; P = 0.025).
Table 2.
Univariate analysis of predictors of positive electrophysiological study
| Factor | Positive (113) | Negative (158) | OR (95% CI) | P |
|---|---|---|---|---|
| Clinical factors | ||||
| Gender male | 68% | 61.3% | 0.74 (0.43‐1.27) | 0.28 |
| Hypertension | 79.6% | 77.8% | 1.11 (0.6‐2.01) | 0.72 |
| Dyslipidemia | 59.3% | 58.2% | 1.01 (0.6‐1.7) | 0.8 |
| Diabetes mellitus | 37.2% | 29.1% | 1.44 (0.86‐2.41) | 0.16 |
| Age (years) | 73.81 ± 9.9 | 74.1 ± 13.6 | — | 0.87 |
| Coronary artery disease | 27.4% | 17.7% | 1.7 (0.91‐3.1) | 0.07 |
| Trauma injury | 44.3% | 42.9% | 1.05 (0.64‐1.74) | 0.82 |
| Absence of prodromal symptoms during syncope | 75.5% | 70.5% | 0.77 (0.44‐1.36) | 0.38 |
| Number of syncope episodes | 2.48 ± 2.16 | 2.41 ± 2.56 | — | 0.83 |
| Basal sinus rhythm | 88.5% | 83.6% | 0.67 (0.32‐1.35) | 0.25 |
| Echocardiography factors | ||||
| LVEF 35%‐50% | 42.1% | 30.6% | 1.6 (1.01‐2.7) | 0.05 |
| LVEF (%) | 54.1 ± 11.8% | 57.4 ± 8.1% | — | 0.008 |
| Left ventricle end‐diastolic diameter (mm) | 50.2 ± 7.9 | 47.2 ± 6.9 | — | 0.004 |
| Left ventricle end‐systolic diameter (mm) | 34.3 ± 8.5 | 30.3 ± 7.5 | — | 0.000 |
| Septum thickness (mm) | 13.1 ± 2.9 | 12.6 ± 2.3 | — | 0.17 |
| Posterior wall thickness (mm) | 11.4 ± 2.1 | 10.9 ± 1.9 | — | 0.07 |
| ECG‐related factors | ||||
| Long PR interval (%) | 40.7% | 17.1% | 3.3 (1.9‐5.9) | <0.0001 |
| PR interval duration (ms) | 199.1 ± 54.9 | 171.0 ± 46.9 | — | <0.0001 |
| QRS interval duration (ms) | 146.6 ± 19.9 | 138.5 ± 13.5 | — | <0.0001 |
| QRS > 150 (ms) | 44.2% | 24.8% | 2.41 (1.43‐4.1) | 0.001 |
| Left bundle branch block (LBBB) | 42.3% | 33.5% | 1.45 (0.86‐244) | 0.16 |
| LBBB plus long PR interval | 43.8% | 11.4% | 5.2 (1.52‐17.74) | 0.001 |
| PR interval (ms) | 197.4 ± 60.2 | 163.8 ± 36.9 | — | 0.002 |
| QRS interval (ms) | 146.5 ± 18.4 | 142.8 ± 13.1 | — | 0.24 |
| Right bundle branch block (RBBB) | 53.6% | 65.2% | 0.62 (0.37‐1.03) | 0.07 |
| RBBB plus long PR interval | 50% | 20.5% | 3.8 (1.7‐8.7) | 0.001 |
| Bifascicular block | 75% | 60.8% | 2.34 (1.08‐5.1) | 0.003 |
| PR interval (ms) | 201.2 ± 51.7 | 173.8 ± 49.5 | — | 0.003 |
| QRS interval (ms) | 148.3 ± 20.6 | 137.1 ± 13.2 | — | <0.0001 |
| Conduction disturbances different than isolated RBBB | 88.4% | 75.5% | 2.39 (1.2‐4.7) | 0.009 |
| LBBB or RBBB plus left fascicular and long PR vs other conduction disease | 64.1% | 47.1% | 1.9 (1.1‐3.2) | 0.01 |
ECG, electrocardiography, OR, odds ratio, LVEF: left ventricular ejection fraction.
Figure 1.
Bars show the rate of positive electrophysiological studies in patients with the presence (gray bars) or absence (white bars) of certain statistically significant echocardiographic or electrocardiographic features
Table 3.
Multivariate analysis of predictors of positive electrophysiological study
| Factor | OR | CI 95% | P |
|---|---|---|---|
| Conduction disturbance different than isolated RBBB | 15.2 | 2.2‐23.4 | 0.005 |
| Long PR interval | 8.65 | 2.98‐25.1 | 0.000 |
| LBBB or RBBB plus long PR and left fascicular block | 4.54 | 1.06‐20.01 | 0.042 |
| Bifascicular block | 4.8 | 1.20‐16.7 | 0.025 |
Abbreviations: CI, confidence interval; LBBB, left bundle branch block; OR, odds ratio; RBBB, right bundle branch block.
4. DISCUSSION
In our series, the diagnostic yield of EPS for bradyarrhythmia in patients with syncope and BBB is moderate (41.7%). This rate is comparable with other series8, 10 with a variation between 38% and 42%. As far as we know this is the largest prospective single‐center study that analyses the diagnostic yield and predictors of electrophysiological (EP) positivity in patients with syncope and wide QRS. The main finding of our study is the relation of positivity of EPS with a conduction disturbance pattern as well as with long PR interval.
In our series, the most powerful predictor of severe disease of His‐Purkinje system is a conduction disturbance different than isolated RBBB (OR 15.2). This finding has not been systematically reported in the literature. General prognosis of isolated RBBB in general population is benign11 and only in presence of axis deviation (due to LAFB or LPFB) the risk of progression to complete AV block is higher.12 It seems reasonable that patients with isolated RBBB have less rate of positive EPS than other conduction disturbance pattern. One old study analyzed the ECG findings in patients with positive EPS. Only 3 over 12 patients with positive EPS had isolated RBBB vs 8 over 14 patients with negative EP test.13 By contrast, another old retrospective study with larger population showed no relation between conduction disturbance pattern and HV interval.14 Finally, the conduction disturbance pattern as predictor of positive EPS has been analyzed in a contemporary study. In this study,10 isolated RBBB had similar diagnostic yield (34.4%) than RBBB plus LAFB (36.2%, P = 0.05) or LBBB (46.2%, P = 0.29). In our series, number of patients with isolated RBBB (52 vs 33, respectively) and number of patients with RBBB + LAFB (102 vs 66, respectively) is larger than in the previous study.10 Therefore, the lack of statistical power of the above‐mentioned study could be the explanation for these differences. In our series, only 25.9% of patients with isolated RBBB had a positive EPS. In these patients, the QRS duration was longer than those with isolated RBBB and negative EP test (148.3 ± 20.6 vs 137.1 ± 13.2 milliseconds, P = 0.001). In contrast, among patients with LBBB, QRS duration was not different in patients with positive vs negative EP test (146.5 ± 18.4 vs 142.8 ± 13.1, P = 0.24). To our knowledge, the QRS duration as a marker of positive EPS in patients with isolated RBBB has not been described before. Several studies suggest that QRS width is related with mortality in patients with heart failure.14 Moreover, QRS width is related to worse prognosis in general population with RBBB.15 Nevertheless, no data is published about QRS width in patients with syncope and RBBB. As QRS duration reflects the total electrical systole of the heart, because of the integrity of left anterior and posterior fascicle in case of isolated RBBB, QRS duration is usually less than in other conduction disturbances as LBBB or bifascicular block. In this sense, a possible explanation of the relation of wider QRS in patients with RBBB and positive EP test could be that this subgroup of patients have not only RBBB but more advanced His‐Purkinje disease although in the surface ECG the pattern is only RBBB.
The second main factor that predicts a positive EPS in our series is a long PR interval (positive EPS 62.9% vs 33.7%; OR 8.65; P < 0.001). PR interval reflects AV nodal conduction time in patients with normal QRS duration.16 However, the location of AV block in case of BBB and long PR interval could be in both AV node or intra or below His bundle.17 Many studies confirmed that long PR interval in case of BBB is associated with multisite conduction delay with involvement of His‐Purkinje system in a high proportion of patients.10, 15, 16 In contrast to QRS duration, long PR interval was associated with higher rate of positive EP test in both RBBB (positive EP test 59 vs 17.1%, OR 3.8; 1.7‐8.7; P < 0.0001), and LBBB (positive EP test 80.8 vs 40.9%, OR 5.2; 1.52‐17.74; P < 0.0001). So in concordance to other studies, long PR interval in case of BBB seems to reflect more advanced conduction tissue disease. Overall, we consider that with our study, there are two groups of patients in which EPS study could be not necessary (depending on clinical profile). First group could be patients with LBBB and long PR interval, in case of suspected cardiac syncope. In these patients, direct implantation of a pacemaker could be considered because of the high rate (more than 80%) of positive EPS. On the opposite, the second group that could avoid EPS is patients with single RBBB without long PR. In these patients, diagnostic yield of EPS is very low (less than 20%) so, in case of suspected arrhythmia‐related syncope, direct ILR implantation should be considered. However, long‐term follow‐up of these patients should be performed to confirm these hypotheses.
Finally, it deserves to be mentioned that the absence of any clinical predictor of positive EPS. Although several studies suggest that the clinical profile of the syncope is a predictor of an arrhythmic etiology,18 in all of these series, the highest value of clinical profile was in patients with normal ECG. In the same line, even in patients with implanted pacemaker ECG remains a powerful predictor of cardiac events.19 In the present study, patients with normal ECG were not included and no clinical predictor of positive EPS was found. Moreover, we have only included patients with EPS. So patients with BBB, but with clinical features of the syncope episode that strongly suggest neurally‐mediated syncope may not have been included in the present study.
4.1. Study limitations
The decision to perform an EPS in a patient with syncope and BBB was left to clinician in charge. In this sense, some patients with highly suggestive neurally‐mediated syncope could have not been included in the study because EPS was not performed. During the study period, Procainamide was changed for Flecainide as IC drug used in order to unmask advanced His‐Purkinje disease. This change could have had some influence resulting in a different diagnostic yield of EP test in relation to different ICD drug used. In our series, very few patients had LPFB (two patients). So the relation of this kind of conduction disturbance with the positivity of EP test cannot be analyzed from our data.
5. CONCLUSIONS
Diagnostic yield of EPS to depict arrhythmia‐related syncope in patients with syncope and BBB is moderate (41%). Type of conduction disturbance pattern in ECG is strongly associated with the result of EP test. Patients with LBBB and bifascicular block has a higher rate of positive EP test than patients with isolated RBBB. Positive EPS in patients with isolated RBBB is related to QRS width. Finally, long PR interval increases the proportion of positive EPS in all kind of ECG patterns in patients with syncope and BBB.
CONFLICTS OF INTEREST
The authors declare no potential conflict of interests.
ACKNOWLEDGMENTS
This work was partially supported by the Instituto de Salud Carlos III—CIBER‐CV Fondos FEDER.
Roca‐Luque I, Oristrell G, Francisco‐Pasqual J, et al. Predictors of positive electrophysiological study in patients with syncope and bundle branch block: PR interval and type of conduction disturbance. Clin Cardiol. 2018;41:1537–1542. 10.1002/clc.23079
Funding information Instituto de Salud Carlos III
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