Does cardiac resynchronization therapy benefit patients with right bundle branch block: cardiac resynchronization therapy has a role in patients with right bundle branch block.

Abstract

HomeCirculation: Arrhythmia and ElectrophysiologyVol. 7, No. 3Does Cardiac Resynchronization Therapy Benefit Patients With Right Bundle Branch Block Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessResearch ArticlePDF/EPUBDoes Cardiac Resynchronization Therapy Benefit Patients With Right Bundle Branch BlockCardiac Resynchronization Therapy Has a Role in Patients With Right Bundle Branch Block Angelo Auricchio, MD, PhD, Joost Lumens, PhD and Frits W. Prinzen, PhD Angelo AuricchioAngelo Auricchio From the Division of Cardiology, Fondazione Cardiocentro Ticino, Lugano, Switzerland (A.A.); Department of Biomedical Engineering, Maastricht University, Maastricht, The Netherlands (J.L.); and Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands (F.W.P.). Search for more papers by this author , Joost LumensJoost Lumens From the Division of Cardiology, Fondazione Cardiocentro Ticino, Lugano, Switzerland (A.A.); Department of Biomedical Engineering, Maastricht University, Maastricht, The Netherlands (J.L.); and Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands (F.W.P.). Search for more papers by this author and Frits W. PrinzenFrits W. Prinzen From the Division of Cardiology, Fondazione Cardiocentro Ticino, Lugano, Switzerland (A.A.); Department of Biomedical Engineering, Maastricht University, Maastricht, The Netherlands (J.L.); and Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands (F.W.P.). Search for more papers by this author Originally published1 Jun 2014https://doi.org/10.1161/CIRCEP.113.000628Circulation: Arrhythmia and Electrophysiology. 2014;7:532–542Cardiac resynchronization therapy (CRT) has been established as a useful therapy for patients with heart failure with abnormal QRS duration and low ejection fraction (EF). Although the vast majority of patients treated with CRT have a left bundle branch block (LBBB) QRS morphology, since the introduction of CRT into clinical practice, a growing number of patients with right bundle branch block (RBBB) QRS morphology or diffuse intraventricular conduction abnormality have been treated.1–19 As shown in Table 1, the most recently conducted studies report a variable proportion of patients with RBBB ≤18%. Thus, these patients represent a sizeable subgroup in need of adjunct therapies on top of the best pharmacological therapy. This percentage is most likely an underestimation of the true number of patients with heart failure and RBBB, because CRT in patients with RBBB has been controversial from the beginning, although QRS widening ≥120 ms was the only ECG selection criterion for CRT. More recently, several studies have shown that non-LBBB patients benefit less from CRT than those with LBBB.20,21 As a consequence, European Society of Cardiology guidelines indicate the use of CRT in non-LBBB patients with a QRS duration >150 ms at class IIa/level of evidence B, whereas guidelines suggest the use of CRT in non-LBBB patients with a QRS duration between 120 and 150 ms at a lower recommendation class (class IIb, level of evidence B).22Table 1. Proportion of Patients With Conduction Abnormality Included in Selected Prospective and Observational Cardiac Resynchronization Therapy StudiesStudyYear of publicationNYHA ClassMeanLVEFMean QRS DurationTotal number of patientsProportion of patients with conduction abnormalityLBBBRBBBIVCDProspective randomized studies* PATH-CHF I120023–421±6174±304293%7%0% PATH-CHF II220032–423±7155±208688%5%6% CONTAK CD320032–421±7155±2749054%14%33% MIRACLE420043–422±6166±2145380%11%9% MIRACLE ICD II52004225±7166±24186NA17%NA COMPANION620043–422158152071%11%18% CARE-HF720053–425†160†81394%5%1% REVERSE820081–226±7151±2368054%8%19% MADIT-CRT920091–224±5152±18181770%13%17% RAFT1020102–323±5158±24186669%9%11%Observational studies* Wokhlu1120092–423±7158±3133867%11%13% Adelstein1220093–423±9175±3063664%9%NA Rickard1320102–422±8156±2033561%11%28% Bilchick1420101–423±6157±261494669%11%20% Varma1520112–423±8163±2112045%26%NA Leong1620123–426±8161±1956184%16%0% Hara1720123–4NA160±2625450%18%32% Kandala1820133–423±6156±2814457%13%30%Survey* Dickstein1920091–427±8157±32243868%6%NACARE-HF indicates Cardiac Resynchronization-Heart Failure; COMPANION, Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure; ICVD, intraventricular conduction disturbance; LBBB, left bundle branch block; LVEF, left ventricular ejection fraction; MADIT-CRT, Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy; MIRACLE, Multicenter InSync: Randomized Clinical Evaluation; MIRACLE II, Multicenter InSync ICD II: Randomized Clinical Evaluation; NA, not available; NYHA, New York Heart Association; PATH-CHF I, Pacing Therapies in Congestive Heart Failure I; PATH-CHF II, Pacing Therapies in Congestive Heart Failure II; RAFT, Resynchronization-defibrillation for Ambulatory heart Failure Trial; RBBB, right bundle branch block; and REVERSE, Resynchronization reVErses Remodeling in Systolic left vEntricular dysfunction.*Prospective randomized controlled studies are reported using the respective acronym, whereas the observational studies and survey are reported according to the first author of the published article.†Median value instead of mean value has been reported.Response by Kenneth Bilchick on p 542Although several factors may be held accountable for the diverse response to CRT in RBBB compared with LBBB, they have not been systematically reviewed. However, several retrospectively conducted studies have suggested that CRT may be beneficial in subgroups of patients with RBBB. In the present article, we are taking a mechanistic approach to evaluate the effect of CRT in patients with heart failure diagnosed with RBBB. Thus, we will review the electrophysiological findings, the mechanical abnormalities observed in patients with RBBB, and finally the clinical results of CRT in this patient subgroup to address a key question: is RBBB an inappropriate indication for CRT or is CRT applied in the wrong way in patients with RBBB?Right and Left Ventricular Electric Activation in Patients With RBBBThe relative fragility and mechanical structure of the right-sided conduction system may explain the high incidence of this conduction delay in the general population without evidence of structural heart disease. In the Framingham study, RBBB and LBBB developed in 70 and 55 patients, respectively, during 18-year follow-up in 5826 healthy individuals.23 The Moli-sani study, which recruited 24 090 subjects in the central-southern region of Italy,24 reported that RBBB was recorded in 589 individuals (2.44%), whereas LBBB was recorded in 181 individuals (0.75%); interestingly, RBBB was more frequent in men (3.4%) than in women (1.0%), whereas LBBB was slightly more frequent in women (0.9%) than in men (0.6%). Furthermore, new onset of RBBB in patients with heart disease may be indicative of aggravation of the heart condition25 and possible association with right ventricular (RV) dysfunction of primary or secondary origin.Insight into electric activation during LBBB and during ventricular pacing (including CRT) has steadily increased during the past years. In contrast, detailed 3-dimensional mapping in patients with RBBB is limited to a single case series published by Fantoni et al26 in 2005. These authors performed extensive measurement of both RV and left ventricular (LV) endocardial electric activation in heart failure patients with RBBB and LBBB. In heart failure patients with RBBB, the earliest ventricular activation site is located in the LV myocardium, usually in the septum. The LV septal activation coincides with the beginning of the QRS complex. After a considerable delay (50–70 ms), the activation arrives at the RV side of the septum because of slow left-to-right transseptal activation. The electric activation of the entire RV occurs slowly, most likely as a result of cell-to-cell conduction: from the septal breakthrough site, the activation front proceeds toward the RV anterior wall and then to the right lateral wall and the outflow tract, which both are the latest activated regions. Because of this activation pattern, RV anterior and lateral regions are delayed with respect to the onset of the QRS complex, thus mirroring on the right side of the heart the pattern that is usually observed in the LV of patients with LBBB (Figure 1). As a result, total RV endocardial activation time in patients with RBBB is much longer (80–120 ms) than in patients without conduction delays (50–80 ms). Because in RBBB much or all of the RV undergoes depolarization after activation of the LV has been completed, the electric forces generated by the RV are not masked by the predominant and largest LV electric forces but now show up as a delayed component in the QRS complex, drawing the characteristic RBBB morphology in the surface ECG (Figure 1).Download figureDownload PowerPointFigure 1. Electroanatomic mapping and surface 12-lead ECG in a patient with right bundle branch block (RBBB; A), in a patient with RBBB masking left bundle branch block (LBBB; B), and in a patient with LBBB (C). The activation sequence is color-coded by 10-ms isochrones (red indicates the earliest activation region, and purple indicates the latest activation region).In some heart failure patients with RBBB, the QRS morphology is significantly different from the characteristic RBBB appearing in otherwise structurally normal hearts. These patients with heart failure show a specific electrocardiographic pattern defined by Rosenbaum et al27 as RBBB masking LBBB, characterized by a broad, slurred, sometimes notched R wave on leads I and aVL, together with a leftward axis deviation frequently noted in LBBB QRS morphology patients as well (Figure 1). In patients with RBBB masking LBBB, electroanatomic mapping data have demonstrated that not only RV activation is abnormally delayed but also LV activation is delayed as much as in patients presenting with LBBB.26 Furthermore, the LV activation pattern observed in these patients resembles the one observed in patients with LBBB (Figure 1). Notably, patients with heart failure presenting with pure RBBB differed from those with RBBB masking LBBB by presenting an LV anterobasal breakthrough in addition to the septal one (Figure 1). Patients with RBBB masking LBBB usually present with a severe biventricular postischemic cardiomyopathy, with large myocardial injury because of significant lesion of the anterior descending coronary artery.RV and LV Mechanical Abnormalities in Animals and Patients With RBBBCanine studies using experimental LBBB have shown that this intervention immediately and persistently reduces LV pump function.28,29 In this regard, less is known about the hemodynamic effect of RBBB. In the 1980s, Yasui et al30 induced experimental RBBB in dogs with normal hearts and in dogs with moderate and severe RV hypertrophy. They found minor influence of RBBB on RV and LV pump function in normal hearts, but significant deterioration if occurring in hearts with RV hypertrophy: RBBB increased RV end-diastolic pressure, RV dP/dtmax, and stroke volume. This deterioration was related to the duration of the QRS complex.30 In this model, LV function was hardly affected. These data are important because they indicate that RBBB may affect RV function, the forgotten ventricle; however, few data are available on RV systolic function in patients with heart failure, alone or in combination with RBBB, LBBB, and CRT. However, it is important to notice that RV hypertrophy is rarely observed in adults patients with systolic heart failure; therefore, it makes it difficult to completely translate in patients the observation by Yasui et al.30Byrne et al31 investigated mechanical dyssynchrony in a canine model of RBBB and LBBB in combination with tachypacing-induced heart failure. With LBBB, there was a septal shortening and lateral stretch during early systole followed by septal stretch and lateral shortening later in systole. However, with RBBB, strain was more uniform with little dyssynchrony in early systole and posteroseptal shortening in late systole without reciprocal stretch. Plots of instantaneous strain versus short-axis segment location (representing an instantaneous distribution of strain throughout all myocardial segments at 2 different time points in the cardiac cycle) showed a more sinusoidal strain profile during early systole in the LBBB model, reflecting a larger disparity of strains. For the RBBB case, segment-to-segment variation was noted in late systole but was lower in magnitude than that seen with LBBB. Early systolic strain distribution in RBBB was nearly uniform.31In heart failure patients with RBBB with an indication for CRT, the mechanical abnormalities of right and left ventricle have been rarely reported.17,32 Hara et al17 examined 278 patients with heart failure with any kind of ventricular conduction disturbance and compared the echocardiographic characteristics (assessment of interventricular mechanical delay and speckle-tracking radial strain) with outcome after CRT. Patients with LBBB had the most prevalent and significant degree of radial strain dyssynchrony compared with non-LBBB patients, and patients with RBBB had the least dyssynchrony, even if QRS duration was comparable in patients with LBBB and RBBB. In patients with LBBB, peak radial strain occurred earlier in the anteroseptum and later in the posterior wall than in non-LBBB patients. LV pre-ejection delay and interventricular mechanical delay were greatest in patients with LBBB, but RV pre-ejection delay was greatest in patients with RBBB, whereas the interventricular mechanical delay was usually small in patients with RBBB. All these data indicate minor LV involvement in many patients with RBBB but indeed possible involvement of RV function. Importantly, 17 of 45 patients with RBBB did show LV radial strain dyssynchrony (>130 ms), which might be associated with left anterior hemiblock or other LV conduction abnormalities on top of the RBBB.Outcome of Patients With RBBBMorbidity and mortality of heart failure patients with RBBB QRS pattern are high, although comparative data from epidemiological studies show a slightly better prognosis for patients with RBBB than for patients with LBBB. The Italian Network on Congestive Heart Failure Registry included 5517 patients with heart failure of different causes.33 Data derived from the Italian Network on Congestive Heart Failure database showed that the total 1-year mortality in patients with RBBB was equal to that in patients with narrow QRS complex (11.9%), yet significantly lower than in patients with LBBB (16.1%); notably, patients with RBBB more frequently presented with heart failure of ischemic cause, whereas primary dilated cardiomyopathy was the most frequent cause of heart failure in patients presenting with complete LBBB. Furthermore, outpatients with complete RBBB were older and more frequently had cardiac enlargement and a reduced EF, but RBBB was not correlated with a more symptomatic heart failure. Similarly, data from the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) study showed that LBBB and RBBB conferred an increased unadjusted risk of adverse outcomes, but LBBB was the only significant predictor of death in 1 and 5 years.34The most compelling data about absolute and relative lower hospitalization rate and death rate in heart failure patients with RBBB compared with LBBB have been recently published by Zareba et al20 for the implantable cardioverter-defibrillator (control) group of the Multicenter Automatic Defibrillator Implantation Trial With CRT (MADIT-CRT) study. Notably, MADIT-CRT patients differed from the Italian Network on Congestive Heart Failure Registry patients because they had a lower functional class (New York Heart Association class I or II), had no history of atrial fibrillation, and had no previous major ventricular arrhythmias. The MADIT-CRT investigators presented cumulative probabilities of primary end points, consisting of heart failure event or death, and the secondary end point of death in each conduction groups and according to device type. The patients with LBBB had a nonsignificantly higher risk of primary end points at 3 years compared with the patients with RBBB and intraventricular conduction disturbance (32% versus 19% versus 23%, respectively), a difference that was mainly driven by differences in heart failure events (Figure 2). Interestingly, the risk of the combined end point of either ventricular tachycardia or ventricular fibrillation requiring appropriate therapy or death was not different between LBBB (31%) and RBBB (28%; Figure 2).Download figureDownload PowerPointFigure 2. Two patient examples of different right bundle branch block (RBBB) morphology (A, RBBB masking left bundle branch block [LBBB]; B, RBBB without LBBB) and radial strain dyssynchrony, with ejection fraction (EF) response and long-term outcome after cardiac resynchronization therapy (CRT). Reproduced from Hara et al17 with permission of the publisher (Oxford University Press, 2012).CRT in a Preclinical RBBB ModelThe differential effect of biventricular pacing in the preclinical setting of RBBB or LBBB has been reported by Byrne et al.31 These investigators showed that the improvement in synchrony (and function) with CRT in hearts with RBBB was less than in those with LBBB. In the acute setting, both LV dP/dtmax and stroke work increased by 5% to 10% in the RBBB hearts, which is less than half of the increase in LBBB hearts.35,36 Notably, the mode of CRT did not necessarily require biventricular stimulation. Single-site RV pacing produced similar improvements in global mechanical function and synchrony as with biventricular pacing. Interestingly, significant narrowing of the QRS complex with both RV-only and biventricular pacing did not translate to a large functional improvement. These findings are reminiscent of the effects of biventricular and LV pacing in LBBB hearts, supporting the idea that in CRT pacing of the latest activated ventricle dominates its benefit. An important observation was that RV and biventricular pacing also, more prominently, improved RVEF, suggesting that CRT with underlying RBBB may especially involve improvement of RV function.CRT in Patients With RBBBDuring the past 10 years, there have been some observational studies in patients with RBBB, most of them including ≤100 patients, which assessed the effect of CRT on some surrogate end points of mortality and few on morbidity and mortality directly. Rickard et al13 observed that patients with RBBB who received CRT derived less cardiac reverse remodeling and less symptomatic improvement compared with patients with LBBB. Egoavil et al37 followed up 61 patients with RBBB randomly assigned to CRT or no CRT and found no improvement in aerobic capacity (measured by maximal oxygen consumption) after 6 months. Wokhlu et al11 and Adelstein and Saba12 demonstrated that patients with RBBB receiving CRT had a higher mortality rate and increased progression of heart failure (to transplant or assist device implantation) compared with patients with LBBB.More recently, the results of 2 large US registries including patients with LBBB, intraventricular conduction disturbance, and RBBB have been published. Bilchick et al14 used the data from the Medicare ICD Registry between 2005 and 2006 to characterize prognosis after CRT defibrillator (CRT-D) and to assess the relationship between clinical factors measured at the time of implantation and outcomes after CRT-D in ≈15 000 Medicare patients.14 In particular, they tested the hypothesis that patients with RBBB have significantly worse outcomes after CRT-D implantation than those with LBBB. Among all patients receiving CRT-D, RBBB morphology was among the most powerful predictors of outcome, even after adjustment for QRS width and other covariates. RBBB had significantly higher short-term and long-term adjusted hazards for death among all patients with CRT-D. RBBB had twice the adjusted hazard for death (hazard ratio [HR], 1.99; P=0.001) as LBBB. An even larger study also using Medicare data between 2006 and 2009 explored the outcome in 24 169 patients receiving CRT-D. This study showed that mortality was lowest in patients with LBBB and QRS duration >150 ms and worse in LBBB with QRS duration of 120 to 149 ms (HR, 1.30) and even worse in patients with non-LBBB morphology with QRS duration >150 ms (HR, 1.34) and 120 to 149 ms (HR, 1.52).21As far as meta-analysis is concerned, Sipahi et al38 performed a large meta-analysis on randomized CRT trials with a total of 5356 patients. Within this study, 1233 patients had non-LBBB conduction abnormalities that were randomly assigned to CRT or no-CRT, a size that is comparable with the major individual CRT trials such as Comparison of Medical Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) and Cardiac Resynchronization-Heart Failure (CARE-HF). They found that there was no trend for reduction in clinical events in this non-LBBB patient category. However, it important to emphasize that this meta-analysis was of little value to establish the role of CRT in patients with RBBB because it was underpowered to estimate the clinical effects of patients with RBBB alone as evidenced by a relatively wide 95% confidence interval (0.69–1.20) for a meta-analytic HR.Taken together, none of the observational studies and the meta-analysis published till date were able to demonstrate a significant CRT benefit in patients with RBBB. However, if one considers the MADIT-CRT study results in the control arm, which showed a better outcome in RBBB than in LBBB patients but a larger mortality in RBBB CRT-treated patients than in LBBB CRT-treated patients observed in both Medicare registries, one may even think of an excess in mortality because of CRT in patients with RBBB.CRT in a Subset of Patients With RBBBHaving said this, all above does not completely rule out moderate improvements in subsets of patients with RBBB. Several studies have characterized such patient subsets, either by echocardiographic criteria or by specific ECG pattern. In one of the earliest case series, Garrigue et al39 reported a beneficial response to CRT (eg, reduced LV end-diastolic diameter, decreased mitral regurgitation, and improved aortic time-velocity integer) but only in RBBB subjects with concomitant LV intraventricular dyssynchrony. Chandra et al40 reported in 44 patients that the presence of concomitant left hemiblock among patients with RBBB referred for CRT was associated with greater response to therapy (defined as improvement in LVEF ≥5% or New York Heart Association class). Varma15 studied the inferolateral LV activation delay, as measured by the distance between QRS onset and the intrinsicoid of the LV ECG in patients with LV dysfunction and RBBB versus LBBB. In that study, the QRS duration correlated well with the inferolateral LV activation delay in both groups, although somewhat more strongly in patients with LBBB. Therefore, at wider QRS durations, patients with non-LBBB morphologies are likely to have significant LV activation delay, an electric substrate amenable to resynchronization. Similarly, in a more recent study, it has been shown that in the subgroup of RBBB patients with mechanical dyssynchrony (radial strain) similar to those of the patients with LBBB, a much favorable response to CRT as given by death, implantation of ventricular assist device, and heart transplantation was found.17 Also, the increase in LVEF and the reduction of end-systolic volume in patients with RBBB showing radial dyssynchrony were similar to that noticed in typical patients with LBBB. In contrast, those RBBB patients without significant radial dyssynchrony showed an unchanged LVEF and even a progression of LV remodeling process.17 Kandala et al18 have recently reported about the use of LV lead electric delay (LVLED), measured intraprocedurally as the interval between QRS onset on the surface ECG to the peak of sensed electrogram on LV lead. Among 144 patients, heart failure hospitalization was higher in non-LBBB compared with LBBB patients (43.5% versus 24%; P=0.015). However, in both LBBB and non-LBBB patients, those with long LVLED had a lower heart failure hospitalization than those with short LVLED (36% versus 61%; P=0.026). In adjusted Cox proportional hazards model, the long LVLED in LBBB and non-LBBB was associated with an improved outcome. Specifically, in non-LBBB, LVLED ≥50% of QRS duration was associated with improved event-free survival with respect to time to first heart failure hospitalization (HR, 0.34; P=0.011) and composite outcome (HR, 0.41; P=0.019). Finally, the most recent report by the MADIT-CRT investigator41 found that subjects with RBBB without left anterior fascicular block experienced greater improvement in cardiac function after 12 months of CRT-D than those with left anterior fascicular block. In contrast, there was no difference in clinical outcomes (ie, death or heart failure admissions) between RBBB subjects with or without a left anterior fascicular block pattern on the surface ECG, despite significant improvements in cardiac function by echocardiography. Therefore, this study seems to run counter to the aforementioned studies, because a close reading of Figure 1 of Tompkins et al41 shows that the patient presenting with left anterior fascicular block also has ECG features of the so-called RBBB masking LBBB by Rosenbaum et al27: broad, slurred, sometime notched R wave on leads I and AVL, with a leftward axis deviation. There is no clear explanation for these apparently opposite findings.In previous studies, the CircAdapt model of the human heart and circulation (www.circadapt.org) proved to be a useful tool to investigate the mechanism of CRT in heart failure patients with LBBB.42,43 Here, we used the CircAdapt model to simulate CRT in the failing heart with different degrees of RBBB, LBBB, or with a combination of both conduction abnormalities. First, a simulation of a failing heart with decreased ventricular contractility and synchronous ventricular activation was obtained as described previously.43 Second, different degrees of RBBB were simulated by imposing dyssynchronous RV free wall activation up to a maximal local activation delay of 156 ms. In addition, different degrees of (coexistent) LBBB were simulated by imposing a septal-to-lateral wall activation delay up to a maximum value of 180 ms. Finally, CRT was applied by imposing the same biventricular pacing protocol to all simulations as published previously by Lumens et al.43Figure 3 summarizes all the baseline activation sequences simulated and also illustrates the general activation pattern used for CRT. Furthermore, Figure 3 shows for all simulations the acute hemodynamic response to CRT, defined as the relative change of stroke volume with respect to baseline (63 mL). Table 2 summarizes global cardiac function during baseline and after CRT for the synchronous failing heart (NO DELAY) and for 3 dyssynchronous failing hearts (RBBB 156, LBBB 180, and RBBB 156 and LBBB 180). In general, these simulation data support the previously reviewed clinical observations that pure RBBB without LV electric dyssynchrony is not a substrate that should be treated with conventional CRT. Only when sufficient LV dyssynchrony substrate coexists, however, acute response to CRT increases to clinically relevant positive values.Table 2. Global Cardiac Function During Baseline and After CRT for the Synchronous Failing Heart and for 3 Dyssynchronous Failing Hearts Presenting With RBBB and LBBBFunction IndexNO DELAYRBBB 156LBBB 180RBBB 156 and LBBB 180Baseline*CRTBaseline*CRTBaseline*CRTBaseline*CRTHR, bpm8080808080808080AV delay, ms150150150150150150150150SV, mL6359636363736375RVEF, %3837363628332933LVEF, %3029302925292629LVEDP, mm Hg2423242742394040The value of conduction delay within each ventricle is arbitrary and is indicated in milliseconds. AV delay indicates atrioventricular delay; CRT, cardiac resynchronization therapy; HR, heart rate; LBBB, left bundle branch block; LVEDP, left ventricular end-diastolic pressure; LVEF, left ventricular ejection fraction; NO DELAY, synchronous failing heart; RBBB, right bundle branch block; RVEF, right ventricular ejection fraction; and SV, stroke volume.*Homeostatic control was active during all baseline simulations so that mean arterial pressure and cardiac output were constant (ie, 92 mm Hg and 5 L/min, respectively) in these simulations.Download figureDownload PowerPointFigure 3. Acute hemodynamic response to conventional biventricular (BiV) pacing in various computer simulations of a failing heart with synchronous ventricular activation, right bundle branch block (RBBB), left bundle branch block (LBBB), or a combination of RBBB and LBBB. Note that cardiac resynchronization therapy (CRT) hardly improves or even deteriorates cardiac pump function in hearts with RBBB in the absence of sufficient coexistent left ventricular (LV) activation delay. RV indicates right ventricular; and RVA, right ventricular apex.Implication for the Deployment of CRT in Patients With RBBBAfter reviewing the available data on RBBB, there is a legitimate question to be addressed: is RBBB an inappropriate indication for CRT or is CRT applied wrong in patients with RBBB? The suitability of CRT for a patient subgroup, such as RBBB, is important because the therapy is relatively