Although early repair of congenital lesions has significantly improved outcomes and survival, right ventricular (RV) dysfunction has been cited as driving morbidity and mortality.1Sanders J.L. Koestenberger M. Rosenkranz S. Maron B.A. Right ventricular dysfunction and long-term risk of death.Cardiovasc Diagn Ther. 2020; 10: 1646-1658Crossref PubMed Scopus (0) Google Scholar,2Brida M. Diller G.-P. Gatzoulis M. Systemic right ventricle in adults with congenital heart disease.Circulation. 2018; 137: 508-518Crossref PubMed Scopus (73) Google Scholar RV dysfunction commonly associated with adult congenital heart disease (ACHD), as the RV is exposed to high pressures and volumes from birth, leading to both systolic and diastolic dysfunction, which ultimately results in right heart failure (RHF).3Harrison A. Hatton N. Ryan J.J. The right ventricle under pressure: evaluating the adaptive and maladaptive changes in the right ventricle in pulmonary arterial hypertension using echocardiography (2013 Grover Conference series).Pulm Circ. 2015; 5: 29-47Crossref PubMed Scopus (23) Google Scholar RHF in congenital conditions such as tetralogy of Fallot (ToF), Ebstein’s anomaly, transposition of the great arteries, and arrhythmogenic RV cardiomyopathy is a principal cause of death.4Guihaire J. Haddad F. Mercier O. Murphy D.J. Wu J.C. Fadel E. The right heart in congenital heart disease: mechanisms and recent advances.J Clin Exp Cardiol. 2012; 8: 1-11PubMed Google Scholar While cardiac resynchronization therapy (CRT) has been studied extensively for left-sided heart failure, little is known regarding electromechanical dyssynchrony of the failing right heart. Electromechanical dyssynchrony has been associated with worse outcomes in this population.5Stefanescu A. DeFaria Yeh D. Dudzinski D.M. Heart failure in adult congenital heart disease.Curr Treat Options Cardiovasc Med. 2014; 16: 337Crossref PubMed Scopus (7) Google Scholar,6Gatzoulis M.A. Till J. Redington A. Mechanoelectrical interaction in tetralogy of Fallot: QRS prolongation relates to right ventricular size and predicts malignant ventricular arrhythmias and sudden death.Circulation. 1995; 92: 231-237Crossref PubMed Google Scholar Further, the degree of QRS widening in right bundle branch block (RBBB) has a well-described impact on the risk of malignant ventricular arrhythmias and sudden cardiac death in ToF. In patients with complex RBBB, the region of latest ventricular activation, in contrast to those with left bundle branch block (LBBB), is the lateral free wall of the RV. Electrical resynchronization would thus be achieved by pacing this portion of the heart in a manner similar to left ventricular (LV) leads for proper RV CRT. This analysis sought to determine the feasibility and short-term outcomes of RV CRT in patients with ACHD with evidence of RV dysfunction plus RBBB. While this is not the first study to examine RV CRT in congenital heart disease, our present work uses a novel technical refinement by using a septal RV sensing lead for timing rather than simple reliance on fusion of single-site RV pacing with native conduction. A cohort of adult patients with ACHD, who have undergone repair of congenital lesion(s), presenting for resynchronization with RBBB were analyzed. Patients were identified at Emory University Hospital between 2015 and 2020. Patients with ACHD were considered for RV resynchronization if they had significant RV dysfunction, evidence of heart failure despite optimal medical therapy, no reversible lesion for repair, and RBBB. Patients were evaluated before resynchronization with 12-lead electrocardiograms and echocardiograms. Those with QRS duration >150 ms and diminished ventricular function were considered for resynchronization therapy. Before implantation, all patients were discussed at our institution’s weekly congenital conference, which is standard for any high-risk or nonstandard or compassionate-use surgical procedures in patients. Careful attention was paid to the optimization of filling pressures and medical therapy. Patients were optimized by the adult congenital service before the procedure, including right heart catheterization if deemed necessary. Patients were close to their dry weight before the procedure and continued to follow outpatients with adult congenital and heart failure clinics for heart failure management. The research reported in this article adhered to the Helsinki Declaration guidelines. The procedure consisted of placing a standard pacing or defibrillator lead on the RV septum. The resynchronizing “LV lead” was an IS-1 active fixation lead that was guided to the lateral and basal free wall of the RV. This was achieved by the used of stylets or with the aid of a curved introducer sheath. The interval from QRS onset to RV lead activation (measure of right bundle branch conduction time) was used to guide lead positioning to maximize lead distance and to give the narrowest QRS. V-V timing and atrioventricular (AV) timing were adjusted at the time of implantation to further narrow the QRS. Serial electrocardiograms and echocardiograms were followed over time to assess changes in QRS duration and RV and LV function, respectively. The systemic ventricular ejection fraction was measured using the biplane Simpson’s method, and the RV fractional area change was calculated using the area difference between RV end-diastolic and end-systolic areas. RV outflow tract velocity time integral and LV outflow tract velocity time integral were measured. RV global longitudinal strain (GLS), degree of tricuspid regurgitation (TR), and RV systolic pressure were also assessed. Continuous data were tested for normality using the Kolmogorov-Smirnov and Shapiro-Wilk tests. The normally distributed variables are reported as means ± SDs. Conversely, the median is reported for skewed continuous variables. Categorical variables are reported as frequencies with their respective percentages. Pre- and post-values were considered to be dependent continuous variables. Accordingly, a paired sample t test was used to compare the means of the values before and after the procedure. As all variables were normally distributed, the Wilcoxon signed-rank test was not applied. Values are reported with a 95% confidence interval with statistical significance set at P ≥ .05. All statistical analyses were performed using SPSS version 28 (IBM Corporation, Armonk, NY). Six patients (2 female, 4 male; mean age at RV CRT 42 ± 11 years) with previously repaired ToF (n = 4) and Ebstein’s anomaly (n = 2) were studied. The mean time to follow-up was 38.4 ± 36.4 months. Individual patient characteristics and anatomy are summarized in Table 1. Patient 6 was lost to follow-up, and we were unable to obtain longitudinal imaging parameters for this patient. All patients undergoing resynchronization presented with moderate to severe right systolic ventricular dysfunction in the setting of native AV nodal conduction and RBBB. Three patients in the cohort underwent preimplantation right heart catheterization. Responses to resynchronization therapy are provided in Table 2.Table 1Patient anatomy and clinical dataPatient no.Age (y)SexAnatomyToFPatient 133FToF with complete repair, PVR, atretic coronary venous systemPatient 245MToF with a Blalock Taussig shunt operation and then repair, PVRPatient 326MToF with early repair, PVR with later fenestrated endograft facilitated PVR, gene-positive HCMPatient 442MToF with complete repair, CAD with known LAD CTO and RCA ostia from the left cuspEbstein’s anomalyPatient 550FEbstein’s anomaly, repaired secundum ASDPatient 656MEbstein’s anomaly, TVR × 2ASD = atrial septal defect; CAD = XXXX; CTO = chronic total occlusion; F = female; HCM = hypertrophic cardiomyopathy; LAD = XXXX; M = male; PVR = pulmonary valve replacement; RCA = XXXX; ToF = tetralogy of Fallot; TVR = tricuspid valve replacement. Open table in a new tab Table 2Measured outcomes pre– and post–RV CRTOutcomePre–RV CRTPost–RV CRT95% CIPNYHA class3.0 ± 0.61.8 ± 1.20.29 to 2.75.01QRS (ms)200.7 ± 58.0127.3 ± 15.50.009 to 2.06.05TAPSE (mm)1.6 ± 0.71.9 ± 0.7−1.67 to 0.32.19RV FAC (%)31.4 ± 10.131.5 ± 9.8−0.89 to 0.86.97RVEF (%)41.0 ± 12.848.2 ± 11.6−5.77 to 0.97.002RV GLS (%)−9.5 ± 4.8−16.4 ± 4.00.69 to 4.69.004RVET (ms)314.7 ± 17.9304.3 ± 58.5−0.60 to 1.02.62RVOT VTI (cm)15.4 ± 7.817.3 ± 9.2−1.02 to 0.60.61RVSP (mm Hg)49.2 ± 16.843.8 ± 9.5−11.3 to 22.2.44LVEF (%)38.3 ± 13.346.8 ± 12.8−1.33 to 0.38.28LVOT VTI (cm)17.2 ± 5.120.8 ± 5.2−1.75 to 0.15.10Values are presented as mean ± SD. P values ≤.05 deemed significant. n = 5 for all parameters, aside from all 6 patients with pre– and post–RV CRT QRS durations recorded.CI = confidence interval; CRT = cardiac resynchronization therapy; FAC = fractional area change; GLS = global longitudinal strain; LVEF = left ventricular ejection fraction; LVOT VTI = left ventricular outflow tract velocity time integral; NYHA = New York Heart Association; RV = right ventricular; RVEF = right ventricular ejection fraction; RVET = right ventricular ejection time; RVOT VTI = right ventricular outflow tract velocity time integral; RVSP = right ventricular systolic pressure; TAPSE = tricuspid annular plane systolic excursion. Open table in a new tab ASD = atrial septal defect; CAD = XXXX; CTO = chronic total occlusion; F = female; HCM = hypertrophic cardiomyopathy; LAD = XXXX; M = male; PVR = pulmonary valve replacement; RCA = XXXX; ToF = tetralogy of Fallot; TVR = tricuspid valve replacement. Values are presented as mean ± SD. P values ≤.05 deemed significant. n = 5 for all parameters, aside from all 6 patients with pre– and post–RV CRT QRS durations recorded. CI = confidence interval; CRT = cardiac resynchronization therapy; FAC = fractional area change; GLS = global longitudinal strain; LVEF = left ventricular ejection fraction; LVOT VTI = left ventricular outflow tract velocity time integral; NYHA = New York Heart Association; RV = right ventricular; RVEF = right ventricular ejection fraction; RVET = right ventricular ejection time; RVOT VTI = right ventricular outflow tract velocity time integral; RVSP = right ventricular systolic pressure; TAPSE = tricuspid annular plane systolic excursion. There were no acute complications in this cohort. There were no subacute complications including pocket infection in this cohort. With the exception of 1 patient without follow-up data, there were no instances of worsened TR. RV lateral wall lead parameters were all stable and acceptable during the follow-up period. The New York Heart Association (NYHA) score decreased from 3 to 1.8 (P = .01), reflecting a significant improvement in functional status of these patients after CRT defibrillator (CRT-D) placement. None have had device-related complications to date (Figure 1). The RV ejection fraction increased post-CRT (41.0% ± 12.8% to 48.2% ± 11.6%; P = .002). The LV ejection fraction also improved post-CRT (38.3% ± 13.3% to 46.8% ± 9 12.8%; P = .28), but did not reach statistical significance, likely because it was underpowered (see the Online Supplement for representative images). Tricuspid annular plane systolic excursion increased post-CRT (1.6 ± 0.7 to 1.9 ± 0.7; P = .19), but did not reach statistical significance. The degree of TR improved post-CRT, but did not reach statistical significance (Figure 1). RV GLS improved significantly from −9.5% ± 4.8% to −16.4% ± 4.0% (P = .004). Individual variations in RV ejection fraction and RV GLS pre- and post-CRT are shown in Figure 2. RV CRT significantly decreased the QRS duration from 200.7 ± 58.0 to 127.3 ± 15.5 ms (P = .05) along with loss of RBBB morphology in all patients, reflecting elimination of late RV activation (Figure 3). Patient 1 was born with ToF and had undergone complete repair with pulmonary valve replacement (PVR) in childhood. She presented at 33 years of age with heart failure due to severe RV dysfunction, with a normally functioning pulmonary valve. She ultimately underwent RV CRT device placement. She had an atretic coronary venous system and had a septal defibrillator lead, with a lateral tricuspid annular pacing lead as the resynchronizing lead, and a right atrial lead placed in the lateral right atrium. Her symptoms improved at 6-month follow-up and subsequently at 2 years. The QRS duration also decreased from 198 to 120 ms. Patient 2 was born with ToF and had undergone a Blalock-Taussig shunt operation, followed by repair and PVR in childhood. Because of RHF and a prolonged HV interval at electrophysiology study, a CRT-D using the RV resynchronization technique. His symptoms significantly improved from NYHA class III to I and QRS duration decreased at subsequent interval follow-up visits and at 6 years. Patient 3 was born with ToF and had undergone early repair and PVR. He had undergone implantable cardioverter-defibrillator to CRT-D upgrade, with tunneling from the right internal jugular vein because of bilateral occlusions (Figure 3, Figure 4). His symptoms improved from NYHA class III to II and QRS duration decreased. Patient 4 had ToF with complete repair. This patient underwent lateral RV resynchronization, and his QRS duration shortened at 1 year (from 180 to 138 ms). Patient 5 had Ebstein’s anomaly and repaired secundum atrial septal defect. This patient had retained severe Ebstein’s anomaly, severe TR, and severe right atrial and RV enlargement, with RV plication above the tricuspid valve below the junction of the atrium. This patient’s case was discussed at the institutional combined medical and surgical conference for consideration of tricuspid annuloplasty, tricuspid valve replacement, right atrial plication, possible Glenn operation if needed, and epicardial biventricular pacemaker due to wide QRS, symptoms, and dyssynchrony. Ultimately, it was deemed that she would benefit from ventricular synchrony first to reduce the risk for valve surgery. The case required an unusually shaped stylet with a reverse curve to implant on the basal lateral wall. Her QRS duration shortened and NYHA class improved at interval follow-up visits and at 7 years. After successful RV CRT device implantation, the plausibility of TVR was revisited. Patient 6 had Ebstein’s anomaly and tricuspid valve replacement twice. The patient underwent upgrade of implantable cardioverter-defibrillator to CRT-D. The patient was at the late stage of various disease processes and was lost to follow-up. This patient did not have post–RV CRT imaging measurements; however, an electrocardiogram was obtained post–RV CRT. We evaluated the effects of RV CRT aimed to restore RV synchrony in 6 symptomatic patients with chronic RV failure due to either repaired ToF or Ebstein’s anomaly and RBBB. RV CRT was associated with improvement in NYHA functional class, QRS duration, and RV function over time (ranging from 1-year to 7-year follow-up time). These findings validate feasibility and suggest an important emerging role for RV CRT in adults with congenital heart disease and RHF. RV dyssynchrony occurs in a vast majority of repaired ACHD and is attributed to a combination of congenital anatomy and surgically induced RBBB.7Diller G.P. Okonko D. Uebing A. Ho S.Y. Gatzoulis M.A. Cardiac resynchronization therapy for adult congenital heart disease patients with a systemic right ventricle: analysis of feasibility and review of early experience.Europace. 2006; 8: 267-272Crossref PubMed Scopus (73) Google Scholar,8Janousek J. Kovanda J. Lozek M. et al.Pulmonary right ventricular resynchronization in congenital heart disease.Circ Cardiovasc Imaging. 2017; 10e006424Crossref PubMed Scopus (33) Google Scholar RBBB pattern is a common conduction abnormality in congenital cardiac lesions.9Khairy P. Marelli A. Clinical use of electrocardiography in adults with congenital heart disease.Circulation. 2007; 116: 2734-2746Crossref PubMed Scopus (45) Google Scholar CRT has been extensively shown to improve hemodynamics in patients with ischemic or dilated cardiomyopathy, especially as these frequently have LBBB morphologies. Patients with RBBB have been traditionally thought to not derive the same benefit from resynchronization therapy as those with LBBB; however, our group and others have described a reasonable left heart failure response to conventional CRT in those with ToF.10Merchant F.M. Kella D. Book W.M. Langberg J.J. Lloyd M.S. Cardiac resynchronization therapy in adult patients with repaired tetralogy of Fallot and left ventricular systolic dysfunction.Pacing Clin Electrophysiol. 2014; 37: 321-328Crossref PubMed Scopus (17) Google Scholar Furthermore, some reports have shown that long-term chronic LV pacing was associated with decreased functional status, impaired RV function, and greater interventricular dyssynchrony in ACHD.11Lecoq G. Leclercq C. Leray E. et al.Clinical and electrocardiographic predictors of a positive response to cardiac resynchronization therapy in advanced heart failure.Eur Heart J. 2005; 26: 1094-1100Crossref PubMed Scopus (222) Google Scholar,12Yeo W.T. Jarman J.W.E. Li W. Gatzoulis M.A. Wong T. Adverse impact of chronic subpulmonary left ventricular pacing on systemic right ventricular function in patients with congenitally corrected transposition of the great arteries.Int J Cardiol. 2014; 171: 184-191Abstract Full Text Full Text PDF PubMed Google Scholar RV resynchronization therapy in repaired ACHD with RBBB may prove beneficial in improving LV function. For nearly all the patients in this cohort, LV function improved at 1 year. While improvement in LV ejection fraction after RV CRT (47% from 38%) did not reach statistical significance in this small study group, we postulate that these patients with RV conduction delay and heart failure may derive LV benefits in larger studies of this technique. Prior studies have shown in activation mapping of patients with repaired ToF and RBBB that there is delayed activation in the RV lateral wall and outflow tract relative to the septal breakthrough.13Horovitz A. De Guillebon M. van Geldorp I.E. et al.Effects of nonsystemic ventricular pacing in patients with transposition of the great arteries and atrial redirection.J Cardiovasc Electrophysiol. 2012; 23: 766-770Crossref PubMed Scopus (16) Google Scholar It has been postulated that while there may be an acute benefit of augmenting RV and systemic performance in repaired congenital lesions with RBBB using biventricular pacing, there are limited studies on outcomes in those who had the resynchronization lead at the RV free wall (RV CRT). RV dyssynchrony has been identified as a target for the treatment of RV heart failure. The mechanism of improvement in RV function with RV CRT is attributed to resynchronization of the septal and RV free wall contraction, leading to improved contraction and reverse remodeling. The optimal pacing site may be determined by recording the delay in local electrical activation with respect to QRS onset. Future studies should develop more standardized and validated assessments for timing of the septal and RV free wall motion as it relates to RV dyssynchrony and clinical symptoms. Optimal RV CRT lead implantation location has not been well defined. Empirical lead placement or lead positioning at the latest site of ventricular activation is a commonly used strategy in clinical practice.14Jalal Z. Sacher F. Fournier E. et al.Right ventricular electrical activation in patients with repaired tetralogy of Fallots.Circ Arrhythm Electrophysiol. 2019; 12e007141Crossref PubMed Scopus (8) Google Scholar Our findings are congruent with those of Janoušek et al.15Janoušek J. Kovanda J. Ložek M. et al.Cardiac resynchronization therapy for treatment of chronic subpulmonary right ventricular dysfunction in congenital heart disease.Circ Arrhythm Electrophysiol. 2019; 12e007157Crossref PubMed Scopus (9) Google Scholar In this brief communication, the authors used single-site pacing at the region of latest delay and showed improved measures of RV function. The implantation technique described in our analysis differs by the placement of the RV septal lead, which was necessary often because of the need for concomitant defibrillation. This laboratory has also shown benefits of temporary pacing in those with ToF. Finally, we considered the impact on the tricuspid valve during these implantation procedures, as additional hardware across this valve would theoretically risk worsening regurgitation. While we did not see this in our cohort, this issue warrants broader and long-term scrutiny. This was a small cohort with heterogeneous ACHD lesions and follow-up times used to demonstrate feasibility and safety. Moreover, end points in the study focused on echocardiographic parameters showing improvement in RV and LV function, which may exhibit variability in interpretation, particularly in the presence of complex congenital geometry. However, the same readers were used. The specifics of AV and VV delay optimization during CRT follow-up were not captured in this entire group. RV CRT using the implantation technique described beneficial effects of RV function in adults with right bundle conduction delay and failing right hearts. The technique demonstrated a favorable safety profile and reasonably long-term favorable clinical profile.
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