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. Author manuscript; available in PMC: 2015 Jun 1.
Published in final edited form as: Circ Arrhythm Electrophysiol. 2014 Jun;7(3):543–552. doi: 10.1161/CIRCEP.113.000747

Left Ventricular Free Wall Pacing: Seldom Right for Right Bundle Branch Block

Kenneth C Bilchick 1
PMCID: PMC4431980  NIHMSID: NIHMS596015  PMID: 24951572

Introduction

In the United States, at least 5 million have heart failure (HF),1 more than 500,000 are diagnosed each year,2 and 2.5 million are hospitalized for their disease.3 In addition, approximately 300,000 patients die from HF every year in the United States,2 and the 5-year survival in the Framingham study in men and women was determined to be 28% and 35%, respectively. These outcomes are known to be modified by QRS duration from the surface electrocardiogram. For example, the 3-year mortality rate in patients with HF and QRS duration greater than 160 ms was reported to be 58% in one study, which represented nearly a 3-fold increase compared with patients having a QRS duration under 120 ms.4 The Italian Network on Congestive Heart Failure (IN-CHF) has reported increased 1-year rates of sudden death and overall mortality in patients with left bundle branch block (LBBB),5 and RBBB has also been found to be predict increased mortality in 7,073 patients referred for nuclear exercise testing.6

Over the past decade, cardiac resynchronization therapy (CRT) implemented as either a pacemaker only (CRT-P) or implantable cardioverter defibrillator (ICD) (CRT-D) has emerged as an common treatment for patients with HF with left ventricular ejection fraction (LVEF) less than 35%, severe HF (New York Heart Association [NYHA] class III-IV status), and intraventricular conduction delays, including both LBBB and RBBB. In particular, the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial7 demonstrated improved survival with CRT-D and a borderline improvement in survival for CRT-P (P=0.056) in patients with a QRS duration of 120 ms or more. The subgroup analysis from the main paper also noted a greater improvement in survival with LBBB versus RBBB. The Cardiac Resynchronization in Heart Failure Study (CARE-HF)8 also enrolled patients with both RBBB and LBBB but required that patients with QRS durations of 120-149 ms have echocardiographic evidence of mechanical dyssynchrony.

More recently, other studies have evaluated CRT in patients with LBBB and RBBB with less severe HF symptoms and/or less severe LV dysfunction. The Multi-center Automatic Defibrillator Implantation-Cardiac Resynchronization Therapy (MADIT-CRT) trial, which compared CRT-D with a standard ICD in 1,820 patients NYHA class I-III patients with LVEF 30% or less and a QRS duration of at least 130 ms, found that patients with LBBB had much better outcomes (HR 0.47 [P<0.001] for the primary endpoint of HF event or death) compared with non-LBBB patients (corresponding HR 1.24 [P=NS]).9 The Resynchronization–Defibrillation for Ambulatory Heart Failure Trial (RAFT) also showed decreased HF hospitalizations with CRT-D in patients with NYHA class II and III HF. These patients had a mean QRS duration of 157 ms with 80% having a LBBB or RV-paced morphology.10 The Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction (REVERSE) trial found decreased rates of HF hospitalization and improved LV remodeling in patients with less severe HF (LVEF 40% or less, NYHA class I-III HF, QRS duration 120 ms or more, and LV end-diastolic dimension of at least 55 mm).11

The prevalence of RBBB has been low in these clinical CRT studies, which has limited interpretation of the RBBB subgroup results. Similarly, in our recent analysis of CRT-D implants in Medicare patients from the original ICD registry maintained by the Iowa Foundation for Medical Care (IFMC) during 2005 and 2006, only 11% of the nearly 15,000 patients with CRT-D implants had a RBBB.12 Until recently, the guidelines for ICDs in HF recommended that patients referred for CRT-D have a QRS duration of 120 ms or more and did not distinguish between patients with RBBB and LBBB.13 This changed recently with the publication of the 2012 guidelines,14 which have now increased the strength of the recommendation for CRT-D in patients with LBBB and weakened the recommendations for CRT-D in patients with RBBB (Table).

Table 1. 2012 AHA/ACCF/HRS Class I and IIa Indications for CRT.

Class I

  • CRT is indicated for patients with LVEF less than or equal to 35%, sinus rhythm, LBBB with a QRS duration greater than or equal to 150 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT.

Class IIa

  • CRT can be useful for patients who have LVEF less than or equal to 35%, sinus rhythm, LBBB with a QRS duration of 120 to 149 ms, and NYHA class II, III, or ambulatory IV symptoms on GDMT.

  • CRT can be useful for patients who have LVEF less than or equal to 35%, sinus rhythm, a non-LBBB pattern with a QRS duration greater than or equal to 150 ms, and NYHA class III/ambulatory class IV symptoms on GDMT

  • CRT can be useful in patients with atrial fibrillation and LVEF less than or equal to 35% on GDMT if a) the patient requires ventricular pacing or otherwise meets CRT criteria and b) AV nodal ablation or pharmacologic rate control will allow near 100% ventricular pacing with CRT

  • CRT can be useful for patients on GDMT who have LVEF less than or equal to 35% and are undergoing new or replacement device placement with anticipated requirement for significant (>40%) ventricular pacing

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GDMT=Guideline-Directed Medical Therapy. With kind permission from Elsevier.14

The present paper will explore the rationale for using QRS morphology and QRS duration to guide the strength of indication for CRT implantation based on prior clinical trials, registries, and physiologic studies. The electromechanical effects of RBBB and LBBB on the RV and LV will also be explored, and clinical outcomes with CRT in RBBB will be reviewed. In particular, the argument is made that there is seldom a role for LV free wall pacing in patients with HF and a RBBB, although the situation becomes more complex when there is additional left-sided conduction system disease and myocardial scar,15,16 both of which can cause additional electrical and mechanical abnormalities in these HF patients. The paper will also explore the relative efficacy of RV versus biventricular pacing in patients with HF and RBBB.

Electrical Activation in Right and Left Bundle Branch Block

Atrioventricular conduction proceeds via the atrioventricular node through the His bundle and the bundle branches. The right bundle branch proceeds along the right interventricular septum and terminates in the Purkinje fibers that extend to the RV apex. In contrast, the left bundle branch courses through the septum and gives rise to the anterior and posterior fascicles, as well as a third branch supplying the mid-LV septum, before continuing into the Purkinje fiber network. In normal hearts, the LV septum is activated before the RV septum. In this way, the septum is activated from the apex toward the base and lateral walls, with an overall conduction time of 50 to 80 ms.17

In patients with HF with RBBB or LBBB, much of the LV must be activated via intramyocardial conduction due to the lack of efficient conduction through the specialized conduction fibers. Electrical conduction patterns in HF and LBBB have been described previously.18-20 From the anterolateral RV, the endocardial conduction proceeds across the septum slowly to activate the LV. The conduction wave then proceeds around a functional anterior line of block with subsequent conduction inferiorly toward the LV apex and eventual activation of the basal posterolateral wall of the LV approximately 80-150 ms after the initial activation of the septum. Patients with conduction times on the higher end of this range typically have longer transseptal conduction times.

With RBBB, the LV septum is activated first, then conduction proceeds across the septum toward the RV. As a result, there is late activation of the basolateral RV. Although this represents the typical activation in RBBB, patients with HF and RBBB based on the 12-lead electrocardiogram may not have this typical activation pattern in the LV. These observations date back to the 1940s from studies by Unger and Richman on what they called LBBB “masquerading” as RBBB.21,22 The surface electrocardiograms in these patients had precordial lead findings consistent with RBBB and limb lead findings consistent with LBBB. Using vectorcardiography, they found that LV activation was different from what was commonly found in RBBB or LBBB. On pathologic correlation, they found evidence of infarction and fibrosis in the septum in the areas of both bundle branches and elsewhere. As a result, Unger concluded that the “masquerade” was really a form of bilateral bundle branch disease.22

A more recent study by Fantoni et al using three-dimensional electrophysiology contact mapping has yielded additional insights into different electrical activation patterns seen in RBBB in patients with HF and scar.23 In this study, electroanatomic mapping of the RV and LV was performed in 100 patients with HF, of whom 6 had RBBB. 5 of the 6 patients with RBBB had ischemic cardiomyopathy, and RBBB patients had significantly worse hemodynamic profiles with a higher NYHA functional class and a lower LVEF. The latest activation in the RV was on the lateral free wall or outflow tract, and RV activation times were significantly longer in RBBB compared with LBBB. Among patients with RBBB, 2 patients had two septal breakthrough sites, while the other 4 had just one septal LV breakthrough site, likely due to left-sided bundle branch disease. Transseptal activation was much quicker in RBBB (2 ms on average, compared with 47 ms in LBBB). As shown in Figure 1 (panel C), the latest-activated site in the LV for LBBB patients was the lateral wall, with activation times in this area ranging from 40-170 ms.

Figure 1.

Figure 1

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Electrical activation contact maps. Electrical maps are shown for HF with RBBB (A), HF with RBBB and left bundle branch disease (B), and HF with LBBB (C). Areas of late activation and time to late activation vary based on the conduction abnormality, as described in the text. With kind permission from John Wiley and Sons.23

In the RBBB example with two septal breakthrough sites (Figure 1, panel A), the latest LV activation site was also the lateral free wall, but the activation time to this area was not as long as the activation delay to this same area in the LBBB example (Figure 1, panel C) based on the color time scale in Figure 1. In contrast, the RBBB example patient (Figure 1, panel B) with only a single more posterior LV septal breakthrough site had a more focal area of delayed electrical activation on the LV anterior wall.

Of note, it is possible that epicardial electrical activation patterns were somewhat different from endocardial activation patterns. In addition, while the LV electrical activation patterns presented in the paper are certainly interesting, the mechanical activation patterns in these patients were not evaluated. Even so, the findings are provocative. Perhaps the most impressive of these findings was the markedly delayed activation of the RV in RBBB compared with LBBB. This has implications for the role of RV pacing in patients with RBBB and HF, as discussed subsequently.

Mechanical Activation in Right and Left Bundle Branch Block

LBBB Mechanics

Ultimately, the most important factor in identifying optimal candidates for CRT is regional mechanical activation due to bundle branch block and overall mechanical LV dyssynchrony.24,25 The mechanical effects LBBB are shown schematically in Figure 2. Muscle activation curves (elastance) are shown for LV regions with early and delayed stimulation.26 When one curve is higher than another, this region of the wall is relatively stiffer and thus can stretch the opposing wall. Subtracting one from the other yields the difference plot, which would be the apparent discoordinated motion of the wall. Septal areas often shorten up to 10% prior to ejection but have minimal subsequent systolic shortening; thereafter, they are stretched. The lateral wall is prestretched up to 15% in early systole and then undergoes systolic shortening.

Figure 2.

Figure 2

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Left ventricular physiology with dyssynchronous HF. The curves are based on ventricular elastance (stiffening). The vertical difference (thin solid line) defines how one wall would push the other to generate dyssynchrony. This is most marked in early systole (isovolumic contraction) and then late at end-systole/early-diastole. With kind permission from Spring Science & Business Media.26

As a result, the principal factors in LBBB that contribute to decreased work in systole and the symptoms of HF associated with mechanical dyssynchrony are lateral wall stretch instead of contraction in early systole and decreased septal work throughout systole associated with late systolic septal stretch instead of contraction. Consequently, in a patient with typical LBBB dyssynchrony, there is simultaneous regional stretch and contraction at any point in the cardiac cycle. As a result, regional circumferential strain curves may resemble a sine wave pattern in dyssynchronous HF, as shown in Figure 3, where negative circumferential strain represents contraction and positive circumferential strain represents stretch.27 Because the goal of resynchronization is to implant a lead in a late-activated, prestretched site on the LV free wall in order to stimulate mechanically late-activated regions to contract on time with the early-activated septum, the degree of opposing regional stretch and contraction influences the likelihood of CRT response.28

Figure 3.

Figure 3

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Regional circumferential strain curves in HF with LBBB. Note the simultaneous stretch (positive strain) and contraction (negative strain) occurring in opposing walls. With kind permission from Elsevier.29

Quantitative Assessment of LBBB Mechanics Before and After Resynchronization

With this in mind, the circumferential uniformity ratio estimate (CURE) was developed to characterize the extent of simultaneous stretch and contraction occurring in the LV as a result of mechanical dyssynchrony. Because CURE is based on Fourier analysis of regional strain, regional times to peak strain do not need to be measured. Fourier transform analysis is based on the principle that complex functions may be approximated by a series of simpler harmonic functions with frequencies that increase with the order of the Fourier term. CURE uses only the relative contributions of the zero and first order Fourier terms to the overall function of circumferential strain plotted against segment. In this way, the zero order Fourier term for the function of circumferential strain plotted against segment is associated with synchrony because it corresponds to a straight line and indicates that circumferential strain in all segments is the same (Figure 4, upper plot). In contrast, the first order term for the circumferential strain versus segment function is associated with dyssynchrony because it corresponds to a low frequency harmonic function that is positive for some segments indicating stretch and negative for other segments indicating contraction (Figure 4, lower plot).

Figure 4.

Figure 4

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The basis for the circumferential uniformity ratio estimate (CURE). Regional circumferential strain (y axis) is plotted again the short axis LV segment (x axis). The plot approximates a negative straight line with synchrony and a sine wave in dyssynchrony. CURE is calculated as described in the text based on regional distribution of circumferential strain. With kind permission from Elsevier.27

CURE makes use of the zero-order power and first-order power from the Fourier analysis of this function to index dyssynchrony as a ratio of zero-order power to the sum of zero-order and first-order power. As the first-order power becomes greater in the case of severe dyssynchrony, the numerator will be much smaller than the denominator, and the CURE will approach 0. In the case of left ventricular synchrony, the first order power will be small, the numerator will be similar to the denominator, and CURE will approach 1. In this way, CURE generates a number between 0 and 1 that reflects the extent of inefficient LV contraction. In fact, CURE as determined from cardiac magnetic resonance has been shown to be highly predictive of CRT response.27,28 In addition, CURE provides superior discrimination of HF with LBBB compared with indices based on time to peak strain.29

Helm and colleagues have recently evaluated the hemodynamic effect on overall synchrony of resynchronization pacing at various sites in the LV in a canine model of HF and LBBB.30 HF was induced with tachycardia pacing, and the left bundle branch was ablated with radiofrequency energy. At each LV pacing site, global cardiac function was assessed with a conductance catheter, and mechanical synchrony was assessed based on cardiac magnetic resonance myocardial tagging to generate the CURE dyssynchrony parameter. Optimal improvements in LV function were achieved with LV lateral free wall pacing sites, as shown in Figure 5. The potential pacing sites on the LV free wall that yielded 70% or more of the maximal global LV function and synchrony (based on CURE) are shown. It is striking that these areas are basically the same, as shown in the overlay panel. In summary, the confluence of pacing sites generating maximal improvements in synchrony by CURE and LV global function supports that CURE is an effective measure for the assessment of optimal pacing effects in LV resynchronization pacing.

Figure 5.

Figure 5

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Optimal LV pacing sites for global function and synchrony in LBBB and HF. The sites for pacing that yield ≥70% of the maximal LV global function and synchrony are shown. At right, the overlay of the sites producing maximal synchrony and function are shown. The confluence of these sites implies that achievement of LV synchrony by CURE results in optimal global LV function. With kind permission from Wolters Kluwer Health.30

Quantitative Assessment of RBBB Mechanics Before and After Resynchronization

A similar canine model was used by Byrne et al to demonstrate the extent of dyssynchrony that results from RBBB as opposed to LBBB.31 The canines underwent tachycardia pacing into HF, with half undergoing catheter ablation of the right bundle branch and the other half undergoing ablation of the left bundle branch. CRT systems with pacing leads in the right atrium, RV, and LV were implanted in all, and the relative effects of RV pacing, LV pacing, and biventricular pacing were assessed in HF with RBBB versus HF with LBBB. At baseline, QRS durations for both RBBB and LBBB HF were approximately twice as long as those for normal animals. The mean LVEFs in RBBB and LBBB were 32.6% and 25.1%, respectively, while the mean RVEFs in RBBB and LBBB were 15.5% and 25.1%, respectively. As shown in Figure 6, the CURE was significantly lower in LBBB (0.58 ± 0.09) compared with RBBB (0.80 ± 0.03) (p<0.05), indicating much less dyssynchrony in RBBB HF compared with LBBB HF.

Figure 6.

Figure 6

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Mechanical synchrony and regional activation in RBBB and LBBB. 3-D mechanical activation maps and plots of time to peak strain as a percentage of the R-R interval are shown for HF with LBBB (panel A) and HF with RBBB (panel B). With kind permission from Elsevier.31

Both RV single site pacing and biventricular pacing similarly reduced the QRS duration in RBBB HF by a mean of 28-34%, while LV only pacing had no effect on QRS duration. As shown in Figure 7, RV pacing and biventricular pacing resulted in improvements in LV dP/dtmax in RBBB HF, but only RV pacing resulted in a significant improvement in CURE from baseline in RBBB HF. Biventricular pacing also prolonged isovolumic LV relaxation in RBBB HF. In addition, the improvement in dP/dtmax with biventricular pacing was much less in RBBB HF compared with LBBB HF. LV pacing alone was harmful in RBBB HF, worsening LV global function and dyssynchrony as assessed by CURE, and LV relaxation. The synchrony achieved with RV pacing and the marked worsening of LV mechanics with LV only pacing together indicate that most of the benefit derived from biventricular pacing in this model was due to the RV pacing component rather than the LV pacing component. Of note, the RVEF improved dramatically with both RV (62.2 ± 15.2%) and biventricular pacing (55.4% ± 13.0%).

Figure 7.

Figure 7

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Effect of RV, biventricular, and LV pacing on LV function in HF with RBBB. The effects of the different pacing modes on CURE, dP/dtmax, stroke work, and tau are shown for RV only pacing, biventricular pacing, and LV only pacing. There is no additional improvement in CURE or LV dP/dtmax with biventricular pacing over RV only pacing in HF with RBBB, and LV only pacing has an adverse effect on these parameters. *p < 0.007 compared with baseline;†p < 0.047 compared with baseline; ‡p < 0.005 compared with LV only pacing; §p = 0.015 compared with LV-only pacing. With kind permission from Elsevier.31

In our own clinical series of 75 patients with CRT referred for cardiac magnetic resonance, the median CURE in patients with RBBB was 0.66 (interquartile range 0.60-0.81), and significant LV reverse remodeling with at least a 15% reduction in the LV end-systolic volume was uncommon in RBBB.28 In addition, 50% of these patients with RBBB and HF experienced the clinical endpoint of death, ventricular assist device, or heart transplantation during a median follow-up of 2.6 years.

Electromechanical mechanisms in RBBB

There are several key physiologic factors that explain why LV free wall pacing resulted in greater hemodynamic improvements in HF with LBBB in these studies. First, RBBB HF is associated with significantly less dyssynchrony than LBBB HF. Second, in the case of pure RBBB HF, the septum rather than the LV free wall contracts later. For this reason, one would not necessarily expect hemodynamic improvements from LV free wall preexcitation in RBBB HF. Third, the LV free wall is large without any other support structure to prevent stretch, while the LV septum has a smaller area and is supported against stretch by the pressure in the RV cavity. As a result, the improvement in LV mechanics in RBBB HF with RV only pacing is significantly less than the improvement in LV mechanics in LBBB HF with LV only pacing.

The discrepant findings of delayed LV free wall electrical activation in RBBB HF as demonstrated by Fantoni et al23 versus the lack of delayed LV free wall activation in the present study also deserve particular comment. It is likely that many of the 6 clinical patients with RBBB HF studied by Fantoni also had coexisting left bundle branch disease, as discussed earlier. This contrasts with the present study by Byrne et al31, which evaluated the effect of resynchronization pacing on LV mechanics in a model of pure RBBB. In addition, there may be some discordance between electrical and mechanical activation, particularly when evaluating the effects of pacing interventions. For example, previous work by Leclercq et al32 showed that while both LV single site pacing and biventricular pacing improved global function in LBBB HF, LV single site pacing actually prolonged the LV electrical activation time, and biventricular pacing shortened the LV electrical activation time.

Clinical Outcomes in Trials, Series, and Registries

RBBB Outcomes in Clinical Trials

One of the largest CRT clinical trial analyses of RBBB was a pooled analysis of 61 patients from the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) and Contak CD trials, of which 34 were randomized to CRT and 27 to the control group.33 These 61 patients amounted to 6% of the total of 1034 patients enrolled in these two trials. Outcome variables included LVEF, NYHA class, 6-minute hall walk distance, Minnesota Living with HF quality-of-life score, and peak oxygen consumption (peak VO2). The only parameter that was improved after 6 months of CRT in RBBB patients was the NYHA class (3.1 to 2.3), while the other more objective parameters did not improve after 6 months. In particular, there was no significant change in the LVEF or peak VO2 after CRT with RBBB. Specifically, peak VO2 in RBBB patients randomized to CRT was 12.7±4.1 ml/kg/min at baseline and 12.4±2.8 ml/kg/min 6 months after CRT (P=0.85); in RBBB patients randomized to the control group, peak VO2 was 13.0±3.6 ml/kg/min at baseline and 13.6±4.0 ml/kg/min 6 months after CRT. Although subgroup results for LBBB were not reported for comparison in this analysis, the change in peak VO2 after 6 months was significantly greater in the CRT group compared with the control group both in the entire MIRACLE trial cohort (1.1 ml/kg/min [95% CI, 0.6 to 0.7 ml/kg/min] v. 0.2 ml/kg/min [95% CI, -0.2 to 0.8 ml/kg/min]; P=0.009)34 and the entire CONTAK-CD cohort (0.8 ± 0.3 ml/kg/min v. 0.0±0.3 ml/kg/min; P=0.030).35 Similarly, the absolute change in LVEF over 6 months was significantly greater in the CRT group compared with the control group in both the entire MIRACLE cohort (4.6% [95% CI, 3.2% to 6.4%] v. -0.2% [95% CI, -1.0% to 0.5%]; P<0.001)34 and the entire CONTAK-CD cohort (5.1% ± 0.7% v. 2.8% ± 0.7%; P=0.020).35 A smaller cohort of RBBB patients just from the MIRACLE trial (analyzed by different investigators) similarly showed subjective improvements in NYHA class with CRT, but again there were no significant differences in the change in peak VO2 6 months after CRT in RBBB patients (1.1 ml/kg/min with CRT v. 2.2 ml/kg/min in controls; P=0.389). In contrast, the change in peak VO2 at 6 months was greater in LBBB patients randomized to CRT compared with controls (1.2 ml/kg/min with CRT v. 0 ml/kg/min in controls; P=0.008).36 LVEF data were not reported in this study. Of note, even the subjective improvement in NYHA class for RBBB patients was marginal in the MIRACLE trial. At baseline, 24% of RBBB patients were class I, and the remaining 76% were class III; after CRT, no patients were class I, 19% of patients were now class IV, 24% of patients were still class III, and 57% of patients were class II. As noted previously, subgroup analyses of the COMPANION trial7 and MADIT-CRT trial9 also did not support a benefit for CRT in patients with HF and RBBB.

RBBB Outcomes in Clinical Series and Registries

With respect to clinical series and registry studies, Rickard et al reported CRT outcomes based on QRS morphology in 542 patients with new CRT implants at a single center.37 Of these patients, 38 (7.0%) had RBBB. Of note, ischemic etiology of cardiomyopathy was present in 76.3% of patients with RBBB and only in 49.5% with LBBB (p< 0.0001), consistent with the recent observation that patients with HF and RBBB tend to have more scar, commonly in an anteroseptal distribution, compared with LBBB patients.38 In LBBB patients, the LVEF increased from 21.9±7.6% to 32.0±13.1%, but the LVEF was similar before and after CRT in RBBB (23.9%±6.8% to 25.8%±10.0%). The change in the NYHA class was also much greater in LBBB patients. Although there were significant differences in mortality when comparing patients with LBBB, RBBB, and an IVCD (16.2% in LBBB, 26.3% in RBBB, and 29.7% in IVCD) over a mean follow-up of 3.4 years based on the logrank test (P=0.04), RBBB was not associated with a statistically significant increase in mortality with either univariate Cox regression (HR=1.46 [95% CI, 0.7 to 3.06]; P=0.71) or multivariate Cox regression adjusted for age, gender, type of cardiomyopathy, baseline QRS duration, renal dysfunction, and baseline EF (HR=1.1 [95% CI, 0.61 to 2.13]; P=0.84).

In addition, one small series of 12 patients with RBBB and concomitant disease of the left-sided conduction system reported improvements in LV dyssynchrony based on tissue Doppler imaging in 9 of these 12 patients, but the overall LVEF in all patients was unchanged at 12 months compared to the baseline measurement (24 ± 6% to 26 ± 8%; P=NS).39 The existence of left-sided conduction system disease was based on ECG morphology and abnormal QRS axes (left axis in 8 patients and right axis in 4 patients). A marginal improvement in the LV end-diastolic diameter was reported, but this is not the currently accepted measure of LV reverse remodeling after CRT, which is a 15% improvement in the LV end-systolic volume. They also reported an improvement in metabolic equivalents before and after CRT, but more objective peak VO2 testing was not reported. Because currently accepted echocardiographic criteria for LV reverse remodeling as a result of CRT were not demonstrated and the study design was observational, this study does not provide strong evidence that patients with RBBB and HF benefit from CRT. It is also remarkable that there was still no overall improvement in LVEF even though all patients had abnormal QRS axes likely due to concomitant left-sided conduction system disease.

A larger single-center series with 636 patients undergoing CRT compared outcomes in the 10% of patients having RBBB with patients having LBBB.40 Survival free of heart transplantation or ventricular assist device was significantly greater in patients with LBBB compared with RBBB, even after adjustment for other covariates in a Cox multivariable survival model (HR 1.75 [95% CI, 1.04 to 2.94]). There was no overall difference in LVEF before and after CRT in patients with RBBB, while patients with LBBB experienced a 22.7% improvement in LVEF.

We recently obtained similar results in nearly 15,000 Medicare patients enrolled in the ICD Registry maintained by the Iowa Foundation for Medical Care in 2005-6.12 Among 14,946 registry patients receiving CRT during this time period, the 1,638 (11.0%) with RBBB had decreased survival compared with patients with LBBB (Figure 8). The hazard ratio for death with RBBB was 1.44 (95% CI, 1.26 to 1.65) after adjustment for other covariates including NYHA class, age, and ischemic cardiomyopathy, which were also strong predictors of decreased survival after CRT.

Figure 8.

Figure 8

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Outcomes after CRT in the Medicare population based on the baseline bundle branch morphology. Kaplan-Meier curves for overall survival are shown in panel A, indicating that patients with RBBB have worse survival after CRT. As shown in panel B, survival after CRT is best for LBBB with nonischemic cardiomyopathy (NICM) and worst for RBBB with ischemic cardiomyopathy (ICM). With kind permission from Wolters Kluwer Health.12

Of particular interest, bundle branch morphology and ischemic cardiomyopathy both had negative independent effects on survival, as also shown in Figure 8. Patients with RBBB and ischemic etiology of cardiomyopathy had the worst prognosis, with an approximately twofold increased hazard for mortality (HR 1.99 [95% CI, 1.75 to 2.26]) compared with patients with LBBB and HF of nonischemic etiology.12 In this regard, it is interesting that the series by Rickard et al showed an increased prevalence of ischemic etiology of cardiomyopathy in patients with RBBB,37 and recent cardiac magnetic resonance data from Strauss et al show that patients with RBBB and HF are more likely to have large anteroseptal scar compared with patients with LBBB and HF.38 This increased scar burden and increased prevalence of ischemic cardiomyopathy associated with RBBB may also help explain why patients with RBBB as a whole tend to have more unfavorable outcomes after CRT than patients with LBBB.

Right Ventricular Resynchronization in RBBB

The study by Byrne et al suggested that sequential atrial-RV pacing is clearly superior to LV pacing in HF with RBBB and also has certain advantages compared with biventricular pacing in this setting.31 RV pacing was also evaluated prospectively in another study of 7 patients with RBBB and RV dysfunction, many of whom had congenital heart disease.41 LV global function was intact at baseline with mean cardiac index 2.85 ± 1.19 L/min/m2. Sequential atrioventricular (RV) pacing was superior to atrial only pacing for both improvement in RV dP/dtmax and LV cardiac index. As shown in Figure 9, the RV dP/dtmax increased by 22% in RBBB patients with RV pacing. This was somewhat less than the 43% increase in LV dP/dtmax with LV free wall pacing in ten patients with HF and LBBB described previously by Nelson et al,42 but actually greater than the 14% increase in LV dP/dtmax with LV free wall pacing in the PATH-CHF-II study.43

Figure 9.

Figure 9

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Effect of RV pacing on RV and LV hemodynamics in patients with RBBB and RV dysfunction. All patients except one had an improvement in cardiac index with RV pacing (panel A). RV dP/dtmax also improved with RV pacing (panel B). With kind permission from Wolters Kluwer Health.41

Also shown in Figure 9, 6 of 7 patients also had increased LV cardiac index with RV pacing. The mean cardiac index with DOO pacing was 3.4 ± 1.4 L/min/m2, which was 17 ± 8% greater than with AOO pacing, and the cardiac index in one patient increased by as much as 44% with RV pacing.41 The potential explanations for this improvement include correction of systolic dysfunction in the LV septum, improvement in LV diastolic performance, and improvement of LV output through correction of the RV functional abnormality. These data are consistent with other the data from the canine study31 and further support the concept that any benefit with biventricular pacing in patients with RBBB and HF may result from the RV pacing rather than LV pacing.

Conclusions

The clinical data on CRT in RBBB and HF are based on subgroup analyses from clinical trials and results from observational series and registries. This allows us to make only associations rather than definitive conclusions regarding the effectiveness of CRT in patients with RBBB and HF. Without an adequately powered randomized clinical trial of CRT in patients with RBBB and HF, there is not sufficient evidence to support the conclusion that there is no role for CRT in these patients. Even so, it is remarkable that the clinical data available have not shown consistent improvement in objective endpoints such as LVEF or peak VO2 with CRT in the setting of RBBB. Furthermore, a large registry study has shown decreased survival after CRT for patients with RBBB and HF compared with those with LBBB and HF. In addition, clinical cardiac magnetic resonance scar imaging data and data from animal models offer additional insights into why patients with RBBB and HF may have less favorable outcomes after CRT. In conclusion, further clinical studies of the role of CRT in patients with RBBB and HF would be of interest in helping to inform appropriate clinical recommendations for potential CRT candidates with RBBB, and assessment of myocardial scar burden with advanced cardiac imaging may also be helpful, as well.

Acknowledgments

Funding Sources: This work was supported by Dr. Bilchick's NIH K23 grant HL094761.

Footnotes

Conflict of Interest Disclosures: None.

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