Right Bundle Branch Block and Electromechanical Coupling of the Right Ventricle: An Echocardiographic Study.

BACKGROUND: A growing body of evidence suggests that the presence of a right bundle branch block (RBBB) is a negative prognostic indicator in patients with and without preexisting heart disease. Even though electromechanical activation of the right ventricle (RV) in patients with RBBB and pulmonary hypertension (PH) has been investigated; a direct comparison of the presence of RBBB, on the duration of RV mechanical systole using echocardiography has not been studied.
MATERIALS AND METHODS: In this retrospective study, we analyzed the echocardiograms of 40 patients by measuring the magnitude and timing of tricuspid annulus plane systolic excursion (TAPSE) and tricuspid annulus systolic velocity (TA S'). Patients were selected to form four groups of ten patients based on the presence or absence of RBBB and PH to determine if RBBB has any effect on the time-to-peak of TAPSE or TA S', which for our purposes serves as a measure of duration of RV mechanical systole.
RESULTS: Our results demonstrate that RBBB leads to a measurable prolongation of TAPSE and TA S' in patients without PH. Time-to-peak of TAPSE or TA S' was not significantly prolonged in patients with PH.
CONCLUSIONS: The results of this pilot study show that RV mechanical systole is prolonged in patients with RBBB, and the addition of PH attenuates this change. Additional prospective studies are now required to elucidate further the electrical and mechanical dyssynchrony that occurs as a result of RBBB, and how these new echocardiographic measurements can be applied clinically to risk stratify patients with RBBB and PH.

INTRODUCTION

The right bundle branch is a rapidly conducting pathway consisting of Purkinje fibers, located on the right side of the interventricular septum, with a major branch crossing the right ventricle (RV) via the moderator band, providing rapid conduction to the RV free wall. Several studies of patients with right bundle branch block (RBBB) have shown that otherwise healthy individuals incur no increased mortality or morbidity.[123] However, the most recent and largest study to date has shown increased all-cause and cardiovascular risk in the general population.[4] In addition, RBBB has been shown to be a negative prognostic indicator in numerous cardiovascular diseases including heart failure, ischemic heart disease, and chronic obstructive pulmonary disease.[45]

It is well-known that RBBB not only results in a late opening of pulmonic valve;[6] but also is responsible for wide splitting of the second heart sound as a result of delayed ejection of the RV.[6] This electromechanical coupling has been investigated using electrophysiological mapping, which has demonstrated how RBBB leads to a delayed onset of depolarization of the anterior and lateral walls of the RV, as well as prolongation of total RV activation.[7] Despite this wealth of data, there is no echocardiographic study that has directly assessed RV mechanical activation in patients with RBBB, aside from strain imaging data that has shown the presence of a delay in the mechanical activation of the RV free wall with respect to the left ventricle (LV) in patients with pulmonary hypertension (PH).[89]

One goal of this study was to further assess the utility of two previously described echocardiographic measures, the time to attain maximal tricuspid annulus (TA) descent during systole and time to attain its maximal systolic velocity using tissue Doppler imaging (TDI). Previously, these two measures not only have been shown to be acceptable surrogates markers of RV systolic function but also useful in assessing RV electromechanical coupling.[910111213] In addition, we utilized these measures to investigate the mechanical differences between patients with PH RBBB, both individually and the interaction between.

MATERIALS AND METHODS

Study design

For this retrospective study, we queried our heart station database and identified patients with a confirmed RBBB by electrocardiography (EKG) and these were then cross-referenced with our echocardiographic database to identify how many of these patients had an echocardiogram.

RBBB was defined by the Minnesota code as a QRS with a duration of ≥120 ms in a majority of beats in any of leads I, II, III, aVL, aVF, plus R’ > R in leads V1 or V2.[14] The mean time interval between the EKG and the echocardiogram was 33 ± 100 days. Controls were selected from our echocardiography database based on matching the gender, body surface area, and the presence of PH.[15]

Only echocardiographic studies with good endocardial border resolution, visualization of the lateral TA for TDI and M-mode interrogation were included for final analysis. In addition, all patients had to be in normal sinus rhythm at the time of the study with no evidence of ectopy or any other arrhythmias. Finally, patients with previous cardiac surgery, presence of a pacer or defibrillator wire in the RV, arrhythmogenic right ventricular dysplasia, right sided myocardial infarctions, or any significant left-sided valvular diseases were excluded in order to assess the isolated effects of RBBB on RV function.

A total of 40 patients met study criteria and were included in the final analysis, 16 patients were eliminated due to low study quality. The study population was comprised of 4 groups of 10 patients to determine the impact of RBBB on RV contractility, according to the presence or absence of PH. Specifically, Group I or control group consisted of patients with neither RBBB nor PH; Group II included patients with RBBB; Group III was composed of PH patients without RBBB; Group IV had patients with both RBBB and PH.

Our Institutional Review Board (IRB #12012604) approved the study (6/29/2014).

Echocardiography

Two-dimensional (2D) echocardiographic studies were performed using commercially available systems (Vivid 7 and 9; GE Medical Systems, Milwaukee, WI, USA). Images were obtained in the parasternal and apical views with the patient in the left lateral decubitus position and in the subcostal view with the patient in the supine position using a 3.5 MHz transducer. Standard 2D, color, pulsed, and continuous-wave Doppler data were digitally acquired in gently held end-expiration and saved in regular cine loop format for subsequent offline analysis.

Prior work has shown that both tricuspid annulus plane systolic excursion (TAPSE) and tricuspid annulus systolic velocity (S’) are useful and reproducible measures of the longitudinal systolic function of RV.[16] Specifically, TAPSE was measured in the apical four-chamber view by aligning the M-mode cursor along the movement of the lateral TA to measure total basal to apical longitudinal excursion during ventricular systole.[111217] The time interval from the lowest to the highest point was measured and will be referred to as the time-to-peak of TAPSE, as shown in Figure 1. The maximal excursion in M-mode is most clearly identified in patients without PH [Figure 1a]. In patients with PH, the M-mode signal is more rounded and the peak not as clear, however, the best estimate was made based on the midpoint of the upward and downward slopes of the curve [Figure 1b]. In a similar fashion, TA S’ was obtained with TDI using the same anatomical orientation as for M-mode examination of TAPSE.[13] We measured the time interval from zero velocity crossing just before the isovolumetric contraction to the systolic ejection of the TA TDI signal was measured and will be referred to as the time-to-peak of TA S’, as seen in Figure 2. Both time-to-peak time intervals were corrected for heart rate using Bazett's formula and expressed in milliseconds.[18]

Figure 1

Representative M-mode images demonstrating (a) measurement of time-to-peak of tricuspid annulus plane systolic excursion in a patient without pulmonary hypertension and (b) in patients with pulmonary hypertension

Figure 2

Representative tissue Doppler imaging image is demonstrating the ease of measurement of time-to-peak of tricuspid annulus systolic velocity. Measurement was made from zero velocity just before isovolumic contraction to systolic ejection. See also early (Ea), and late (Aa) diastolic phases of the cardiac cycle

Continuous wave Doppler was utilized to record the tricuspid regurgitation jet from multiple windows, and the highest velocity was then used to estimate pulmonary artery systolic pressures using the modified Bernoulli equation and an estimate of mean right atrial pressure using the diameter and collapse index of the inferior vena cava and the hepatic venous flow pattern.[111920]

Statistical analysis

All echocardiographic parameters were calculated using the commercially available software Merge Cardio Workstation (Merge Healthcare) and determined by a single observer.

All continuous data are presented as mean with standard deviation. Categorical data are presented as frequencies. Baseline characteristics were compared between groups using ANOVA and Fisher's exact test, for continuous and categorical data, respectively. Echocardiographic measurements were compared are pairs of groups using the two-tailed unpaired t-test.

Reliability of new echocardiographic measures, time-to-peak TAPSE and time-to-peak TA S’, was assessed using the intraclass correlation coefficient. In order to compare reproducibility of a single reader, two patients were randomly selected from each group, and variables of interest were re-measured after a 6 months span. For comparison among different readers, two patients were randomly selected from each group, and a trained and blinded reader measured variables of interest. Intra-class correlation coefficients were calculated using one- and two-way agreement models for comparison between single and multiple readers, respectively.[21] All statistics were calculated in RStudio (RStudio, Inc.).

RESULTS

A complete transthoracic echocardiogram with good endocardial border resolution and visualization of the lateral TA for adequate TDI and M-mode interrogation was obtained in all 40 patients studied. Complete demographics of each patient group can be found in Table 1. As expected, RBBB patients had a longer QRS duration. Furthermore, Group I patients were more likely to be without diabetes while PH patients were more likely to have congestive heart failure. In addition, while PH patients were more likely to be female; those with RBBB were older. Finally, there was no difference in terms of body surface area among the groups.

Table 1

Complete demographics

All measured echocardiographic variables are listed in Table 2. The presence of PH resulted in significantly lower TAPSE (P = 0.039) as seen in Figure 3a, and TA S’ (P = 0.015) as seen in Figure 3b when compared to patients with normal pulmonary pressures irrespective of the presence or absence of a RBBB.

Table 2

Echocardiographic variables

Figure 3

The presence of pulmonary hypertension resulted in significantly lower (a) tricuspid annulus plane systolic excursion (P = 0.039) and (b) tricuspid annulus systolic velocity (P = 0.015)

When analyzing time-to-peak to both TAPSE and TA S’, we found that among patients without PH, the presence of an RBBB resulted in a statistically significant difference of Δ44 ms for TAPSE, P = 0.03 [Figure 4a] and Δ67 ms for TA S’, P < 0.001 [Figure 4b].

Figure 4

The presence of a right bundle branch block resulted in a time-to-peak difference (a) of Δ44 ms for tricuspid annulus plane systolic excursion (P = 0.03) and (b) Δ67 ms for the tricuspid annulus systolic velocity (P < 0.001)

When we examined these same time intervals in patients with PH, similar, yet less significant, differences were noted with regards to the presence or absence of RBBB [Figure 5a and b].

Figure 5

The presence of a right bundle branch block resulted in a time-to-peak difference (a) of tricuspid annulus plane systolic excursion and (b) tricuspid annulus systolic velocity

We finally assessed the reliability of measuring time-to-peak intervals for both TA S’ and TAPSE using the intra-class correlation coefficient. Consistency of the primary reader over time was very good for both measures. Agreement between the primary and secondary reader was very good for time-to-peak TA S’, and fair for time-to-peak TAPSE, as seen in Table 3.

Table 3

Agreement between readers

DISCUSSION

The results of this study indicate that RBBB has measurable effects on RV mechanics. Specifically, there is a delay in the temporal development of maximum systolic velocity of excursion of the lateral TA as measured by the time-to-peak velocity of the lateral TA using TDI. In addition, there is a delay in the temporal development of maximal TAPSE using M-mode. This was statistically significant among patients without PH and nearly so in patients with PH.

Traditionally, RV systolic function has been shown to be the most important prognostic determinant of morbidity and mortality not only in patients suffering from acute pulmonary embolism but also in those patients afflicted with PH.[222324252627] Unfortunately, RV function assessment remains problematic mainly as a result of the chamber's crescentic shape, presence of a separate infundibulum, prominent trabeculations, and dependence of RV function on loading conditions, pericardial effects, as well as RV and LV pressures.[222829] Despite these limitations, echocardiography remains an indispensable day-to-day imaging tool in the assessment of RV systolic function.[11] TA S’ and TAPSE measures are the most useful and reproducible measures of RV systolic function.[91129] Our laboratory has previously validated the use of TDI in assessing RV systolic function by examining the TA S’.[13] In this study, we found TA S’ to be a more reliable signal than TAPSE, especially among patients with PH. The presence of PH tends to cause a slurring of the M-mode signal, with a less well-defined peak from which to measure. This is evidenced by better correlation in time-to-peak TA S’ between observers and within patient groups. The timing of annular events is a crucial measure that reflects intrinsic anatomical and electromechanical differences between both ventricles.[17] Therefore, as utilization of these measurements for the assessment of RV function becomes more widespread, it will be important to take into account delayed or prolonged electromechanical activation due to RBBB as a separate confounder.

In our study, we confirmed the presence of RBBB leads to a delay of RV contraction by comparing measurements of time-to-peak TAPSE and TA S’ between control individuals and patients with RBBB. Furthermore, we showed a there is a trend toward the same in patients with PH and RBBB, but this was not statistically significant [Figures 4b and 5b]. We speculate that the enlarged and hypertrophied RV of PH patients not only have exhausted their remodeling capabilities based on the Laplace principle,[30] but also are incapable of generating effective contractility.[31] These results in PH are in agreement with previous data identifying a reduced longitudinal deformation of the RV free wall in PH when compared to individuals with normal pulmonary pressures.[93032] The results of our analysis suggest a potential mechanism for aforementioned data on increased mortality and morbidity in patients with RBBB in both the general population and patients with other cardiopulmonary diseases that requires additional study to fully elucidate.

Study limitations

Several limitations need to be listed. First, our total number of patients was limited to 40. However, the intent of this study was to demonstrate the validity of this method in identifying temporal differences in RV activation as a result of RBBB. Second, this was a retrospective study, and therefore not all data available had similar timing or quality. For instance, some EKGs were performed on the day of the echocardiogram, and others were separated by a year. Furthermore, there was great heterogeneity of co-existing medical conditions in our small group of patients, owing to the fact that these patients had their echocardiogram performed for purposes other than research. Third, we lacked sequential imaging on these patients that would have been ideal to validate the true utility of these measures; however, the sole purpose was to demonstrate if significant differences were present as a result of the conduction delay. Fourth, our results are not applicable to congenital heart disease; particularly patients with tetralogy of Fallot are known to have residual RV dysfunction, as well as prolonged conduction time, and these patients were not included in the analysis. Finally, it can be argued that even though new echocardiographic modalities might have been more accurate and useful in studying these abnormalities in greater detail, our sole purpose was to utilize a measurement that will be simple and would not incur or require additional off-line measurements.

In summary, the results of this pilot study seem to suggest that RBBB has an effect on the synchrony of RV contraction leading to overall prolongation of mechanical systolic duration and further elucidates the mechanistic differences that may lead to the increased risk seen in patients with RBBB with and without PH. Additional mechanical studies are now required to follow prospectively these patients with RBBB.