Abstract
Background
Cardiac resynchronization therapy (CRT) induces structural and electrical reverse remodeling in patients with heart failure. However, resolution of complete left bundle branch block (CLBBB) following CRT has rarely been described, particularly with serial phonocardiographic assessment.
Case Summary
A 67-year-old man with heart failure associated with atrial fibrillation and CLBBB underwent CRT pacemaker implantation following pulsed-field ablation. Initially, the optimal interventricular (VV) delay required left ventricular pre-excitation, but shifted toward right ventricular pre-excitation after 1 month. Three months after CRT implantation, CLBBB resolved and left ventricular function nearly normalized. Phonocardiography demonstrated an increased peak-to-peak amplitude of the first heart sound and the disappearance of the third and fourth heart sounds.
Discussion
This case illustrates progressive electrical reverse remodeling reflected by serial changes in optimal VV delay settings and phonocardiographic findings.
Take-Home Message
Temporal changes in optimal VV delay settings may reflect recovery of intrinsic ventricular conduction after CRT.
Key words: cardiac resynchronization therapy, chronic heart failure, echocardiography
Visual Summary
Visual Summary.
Progressive Structural and Electrical Reverse Remodeling After CRT
After pulsed field ablation for atrial fibrillation, CLBBB persisted with severe left ventricular mechanical dyssynchrony. CRT pacemaker implantation using the AdaptivCRT algorithm initially applied LV pre-excitation pacing. Serial electrocardiographic and echocardiographic assessments demonstrated progressive QRS narrowing, reduction in left ventricular mechanical dispersion, and improvement in left ventricular ejection fraction. During follow-up, the optimal VV delay shifted from LV pre-excitation to RV pre-excitation, suggesting dynamic changes in ventricular synchrony associated with reverse remodeling. Phonocardiographic findings showed increased S1 amplitude and disappearance of the pansystolic murmur and third/fourth heart sounds, reflecting improved mechanical synchrony and hemodynamic status. Progressive intrinsic conduction recovery ultimately resulted in resolution of CLBBB at 3 months. CLBBB = complete left bundle branch block; CRT = cardiac resynchronization therapy; LV = left ventricular; LVEF = left ventricular ejection fraction; LVMD = left ventricular mechanical dispersion; RV = right ventricular; S1 = first heart sound; VV = interventricular.
Background
Cardiac resynchronization therapy (CRT) is an established treatment for patients with heart failure (HF), reduced left ventricular ejection fraction (LVEF), and a wide QRS complex, particularly complete left bundle branch block (CLBBB), despite optimal medical therapy.1 However, approximately 30% to 40% of patients do not respond to CRT and remain at high risk for adverse outcomes. Among responders, structural reverse remodeling is frequently observed, and electrical reverse remodeling manifested by narrowing of the intrinsic QRS duration has also been reported.2 Nevertheless, complete resolution of CLBBB following CRT has rarely been described.
Phonocardiography, a noninvasive method for assessing cardiac mechanical functions, has recently regained interest with advances in digital recording and signal processing. It may provide additional insights into mechanical synchrony and cardiac function, complementary to conventional imaging modalities.
We present a case of HF with CLBBB and reduced LVEF in which CRT resulted in resolution of CLBBB accompanied by serial phonocardiographic changes, suggesting concomitant electrical and mechanical reverse remodeling.
History of Presentation
A 67-year-old man with acute decompensated HF and progressive exertional dyspnea was admitted to our hospital. His functional status was NYHA functional class III. Electrocardiography revealed atrial fibrillation (AF) with rapid ventricular response and CLBBB (Figure 1A). Chest radiography revealed mild cardiomegaly (cardiothoracic ratio: 53%) and pulmonary congestion (Figure 1B). Transthoracic echocardiography (TTE) demonstrated diffuse left ventricular (LV) hypokinesis, with a left ventricular ejection fraction (LVEF) of 21% and severe nonischemic functional mitral regurgitation (Figure 1C, Videos 1A and 1B). The patient received guideline-directed medical therapy for HF consisting of valsartan (40 mg), bisoprolol (2.5 mg), dapagliflozin (10 mg), and eplerenone (25 mg). Although pulmonary vein isolation using pulsed-field ablation was performed for AF, resulting in restoration of sinus rhythm, HF symptoms with LV dysfunction and CLBBB persisted 1 month later. Therefore, we decided to implant a CRT device.
Figure 1.
Baseline Clinical Findings
(A) Electrocardiogram showing atrial fibrillation with rapid ventricular response and CLBBB. (B) Chest radiograph showing mild cardiomegaly (cardiothoracic ratio: 53%) and pulmonary congestion. (C) Transthoracic echocardiography showing severe nonischemic functional mitral regurgitation. CLBBB = complete left bundle branch block.
Past Medical History
The patient had a history of AF since approximately 60 years of age, hypertension, and recurrent HF requiring 2 hospitalizations within the 6 months before catheter ablation for AF.
Differential Diagnosis
Ischemic heart disease was excluded by coronary computed tomography angiography. Because the LVEF remained markedly reduced despite catheter ablation for AF, tachycardia-induced cardiomyopathy was considered unlikely to be the primary cause of LV dysfunction. Therefore, mechanical dyssynchrony related to CLBBB was considered the main contributor to impaired cardiac function.
Investigations
Blood tests revealed a B-type natriuretic peptide level of 109.5 pg/mL (reference range: 0-18.4 pg/mL). Electrocardiography revealed sinus bradycardia with CLBBB and a QRS duration of 152 ms (Figure 2A). TTE revealed a LV end-diastolic diameter of 58 mm and an end-systolic diameter of 51 mm. The LVEF, calculated using the modified Simpson method, was 35%, and moderate functional mitral regurgitation was observed (Videos 2A and 2B). Speckle-tracking analysis from the apical 4-chamber view showed septal rebound stretch and left bundle branch block pattern (Figure 3A). Left ventricular mechanical dispersion (LVMD) using 3-view longitudinal strain, a quantitative measure of mechanical dyssynchrony, was 128.2 ms. Heart sounds were recorded at the fourth left sternal border using a digital phonocardiogram system (Cardio-EGG, AMI Inc) (Figure 4A). Phonocardiographic analysis revealed a third heart sound (S3) and fourth heart sound (S4) in the low-frequency range (approximately 20 Hz). In addition, a high-frequency pansystolic murmur at approximately 100 Hz was observed.
Figure 2.
Electrocardiographic Changes and Device Position After CRT Implantation
(A to C) Electrocardiograms (A) before CRT pacemaker implantation (QRS duration 152 ms), (B) 5 days after implantation (QRS duration 116 ms), and (C) 1 month after implantation (QRS duration 105 ms). (D) Anterior and right-to-left lateral chest radiography views after CRT pacemaker implantation. CRT = cardiac resynchronization therapy.
Figure 3.
Speckle-Tracking Analysis Demonstrating Improvement in Mechanical Dyssynchrony After CRT
Speckle-tracking analysis from the apical 4-chamber view at (A) pre-CRT pacemaker implantation, (B) 5 days after implantation, and (C) 1 month after implantation. In (A), septal rebound stretch (asterisks), a marker of intraventricular dyssynchrony, and the typical pattern of a left bundle branch block (arrowheads) are shown. Segmental mechanical dispersion derived from 3-view longitudinal strain was 128.2 ms (A), 58.7 ms (B), and 33.6 ms (C). CRT = cardiac resynchronization therapy.
Figure 4.
Serial Phonocardiographic Changes After CRT Implantation
Heart sounds recorded at the fourth left sternal border. Phonocardiograms at (A) pre-CRT pacemaker implantation, (B) 5 days after implantation, and (C) 1 month after implantation, using 2 frequency analysis methods (short-time Fourier transform [STFT] and continuous wavelet transform [CWT]). After CRT device implantation, the amplitude of the first heart sound (S1) increased, with a shift toward higher frequency components. In addition, the third and fourth heart sounds (S3 and S4, respectively) became less prominent over time. The high-frequency pansystolic murmur, consistent with mitral regurgitation, also decreased in intensity. CRT = cardiac resynchronization therapy.
Management
CRT was performed by implanting a CRT pacemaker (Percepta MRI CRT-P, Medtronic). The right ventricular lead was positioned at the interventricular septum without targeting conduction system pacing (Figure 2D). Initial device programming used the AdaptivCRT algorithm, which automatically adjusts atrioventricular (AV) delays to achieve ventricular fusion through LV or biventricular pacing. In addition, valsartan was switched to sacubitril/valsartan (50 mg) 2 days after CRT pacemaker implantation.
Outcome and Follow-Up
Five days after CRT pacemaker implantation, the QRS duration was 116 ms (Figure 2B). TTE demonstrated improvement in LVEF from 35% to 44% and in LVMD from 128.2 to 58.7 ms compared with preimplantation values (Figure 3B, Video 3A). The mitral regurgitation decreased, accompanied by an improvement in leaflet tethering (Video 3B). The patient's blood pressure remained around 110/60 mm Hg before and after CRT pacemaker implantation, suggesting that the reduction in mitral regurgitation was less likely to be attributable to changes in afterload conditions. Marked changes in the heart sound characteristics were also observed (Figure 4B). The peak-to-peak amplitude of the first sound (S1, arbitrary units) increased from 1.20 to 1.29 compared with preimplantation values. In addition, S1 energy shifted toward a higher frequency range. Both S3 and S4 were nearly absent. Furthermore, the high-frequency pansystolic murmur became less prominent. Optimization of the CRT pacemaker settings was performed by measuring the velocity-time integral of the transmitral flow while varying the AV delays (80-150 ms), and the velocity-time integral of the LV outflow tract, and varying the interventricular (VV) delays (−50 to +10 ms). Heart sounds were subsequently recorded at each programmed delay setting to evaluate associated phonocardiographic changes. The echocardiographically optimized AV and VV delays were 130 ms and −10 to −30 ms, respectively. The device was programmed with an adaptive biventricular pacing algorithm (automatic AV delay, fixed VV delay −20 ms).
At the 1-month follow-up, the HF symptoms clearly improved, and the B-type natriuretic peptide level was reduced to 78.8 pg/mL. The QRS duration was 105 ms, and TTE demonstrated further improvement in LVEF to 52% and LVMD to 33.6 ms (Figures 2C and 3C, Video 4). On phonocardiography, the peak-to-peak amplitude of S1 increased from 1.29 to 1.47 compared with 5 days after CRT pacemaker implantation (Figure 4C). In addition, S1 became sharper, and the S1 energy further shifted toward a higher range compared to 5 days after CRT pacemaker implantation. Repeat optimization of the CRT-pacemaker settings showed that the echocardiography-optimized AV and VV delays were 120 ms and +10 ms, respectively. The device was then reprogrammed using the AdaptivCRT algorithm.
At the 3-month follow-up, total ventricular pacing accounted for 98.1%, including 97.1% LV pacing and 2.8% biventricular pacing, resulting in an effective pacing rate of 98.1% after the second CRT optimization. When ventricular pacing was temporarily suspended, the intrinsic QRS complex remained narrow (QRS 101 ms), indicating resolution of the CLBBB (Figures 5A and 5B). The device was maintained using the AdaptivCRT algorithm, and clinical follow-up was continued.
Figure 5.
Resolution of CLBBB With Recovery of Intrinsic Conduction
Electrocardiogram at 3 months after CRT pacemaker implantation (A) during AdaptivCRT algorithm (A pacing, LV pacing), (B) during intrinsic conduction (A pacing, V sensing). A = atrial; CLBBB = complete left bundle branch block; CRT = cardiac resynchronization therapy; LV = left ventricular; V = ventricular.
Discussion
Among CRT recipients, intrinsic QRS duration has been reported to decrease significantly after implantation, whereas the intrinsic PR interval generally remains unchanged.3 Electrical reverse remodeling occurs in approximately 45% of patients undergoing CRT, with a mean intrinsic QRS narrowing of 12 ms.2 Notably, shortening of the intrinsic QRS duration by ≥20 ms has been associated with improved clinical outcomes and echocardiographic response at 1-year follow-up.4 In the present case, the intrinsic QRS duration shortened by 51 ms, accompanied by resolution of CLBBB, leading to near normalization of LVEF. Although the mechanisms underlying electrical reverse remodeling remain incompletely understood, alterations in ion channel distribution, including increased lateralization of connexin 43, the principal gap junction protein involved in phase 0 depolarization and conduction velocity, have been proposed as potential mechanisms, in addition to structural remodeling such as reductions in LV volumes.5
In this case, the process of electrical reverse remodeling was reflected by temporal changes in the optimal VV delay settings after CRT device implantation. Initially, LV pre-excitation was required to achieve optimal hemodynamics; however, the optimal VV delay shifted toward right ventricular pre-excitation at the 1-month follow-up. At the 3-month follow-up, maintenance of a narrow intrinsic QRS during the temporary cessation of ventricular pacing suggested recovery of intrinsic ventricular conduction. The shift in optimal VV delay may reflect improved conduction through the left bundle branch. These findings support the concept of progressive electrical reverse remodeling following CRT.
Frequency-domain analysis of phonocardiography enables the visualization of dynamic functional changes in cardiac mechanics. To our knowledge, only a few reports have described serial phonocardiographic assessments along with CRT device implantation. Following CRT, the S1 amplitude increased, suggesting improved LV function, whereas the disappearance of S3 and S4 was consistent with improved ventricular filling pressures and diastolic function.6
In the present case, catheter ablation was performed for persistent AF before CRT implantation. AF has been associated with a weaker clinical response to CRT and increased all-cause mortality compared with sinus rhythm.7 AF may reduce effective biventricular capture, leading to loss of AV synchrony and rapid, irregular ventricular rate. Restoration of sinus rhythm by catheter ablation may also have contributed to the favorable response to CRT.
Although optimization of medical therapy, including conversion from valsartan to sacubitril/valsartan following CRT implantation, may have contributed to reverse remodeling, early improvements in mitral regurgitation, ventricular synchrony, and serial phonocardiographic findings were observed shortly after CRT pacemaker implantation.
Conclusions
CRT resulted in progressive electrical reverse remodeling with eventual resolution of CLBBB in a patient with HF. Changes in the optimal VV delay settings appeared to reflect the recovery of intrinsic ventricular conduction over time. Serial phonocardiographic findings paralleled the improvements in cardiac function and may provide complementary insights into ventricular synchrony during CRT follow-up.
Data Availability Statement
The data underlying this article are not publicly available given patient confidentiality but may be available from the corresponding author upon reasonable request and with appropriate institutional approval.
Funding support and author disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Take-Home Messages
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CRT may induce progressive electrical reverse remodeling in addition to structural and functional improvements in selected patients.
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Temporal changes in the optimal VV delay settings may reflect the recovery of intrinsic ventricular conduction after CRT pacemaker implantation.
Acknowledgments
The authors acknowledge all the medical staff who contributed to the care of this patient at the Department of Cardiovascular Medicine, Matsuyama Red Cross Hospital.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
Appendix
For supplemental videos, please see the online version of this paper.
Appendix
Baseline Transthoracic Echocardiography
(A) Apical 4-chamber view demonstrating severely reduced left ventricular systolic function with mechanical dyssynchrony. (B) Color Doppler imaging demonstrating severe nonischemic functional mitral regurgitation.
Transthoracic Echocardiography After Pulsed-Field Ablation
(A) Apical 4-chamber view obtained after restoration of sinus rhythm, demonstrating persistent left ventricular mechanical dyssynchrony associated with complete left bundle branch block. (B) Color Doppler imaging demonstrating residual moderate functional mitral regurgitation.
Transthoracic Echocardiography 5 Days After CRT Pacemaker Implantation
(A) Apical 4-chamber view demonstrating improvement in left ventricular ejection fraction (44%) and reduction of left ventricular mechanical dyssynchrony. (B) Color Doppler imaging demonstrating marked reduction of mitral regurgitation.
Transthoracic Echocardiography 1 Month After CRT Pacemaker Implantation
Apical 4-chamber view demonstrating further improvement in left ventricular ejection fraction (52%) with marked reduction of left ventricular mechanical dyssynchrony.
References
- 1.Sapp J.L., Sivakumaran S., Redpath C.J., et al. Long-term outcomes of resynchronization-defibrillation for heart failure. N Engl J Med. 2024;390(3):212–220. doi: 10.1056/NEJMoa2304542. [DOI] [PubMed] [Google Scholar]
- 2.Pilecky D., Duray G.Z., Elsner D., et al. Association between electrical and mechanical remodeling after cardiac resynchronization therapy: systematic review and meta-analysis of observational studies. Heart Fail Rev. 2022;27(6):2165–2176. doi: 10.1007/s10741-022-10234-w. [DOI] [PubMed] [Google Scholar]
- 3.Kwon H.J., Park K.M., Lee S.S., et al. Electrical reverse remodeling of the native cardiac conduction system after cardiac resynchronization therapy. J Clin Med. 2020;9(7):2152. doi: 10.3390/jcm9072152. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Sebag F.A., Martins R.P., Defaye P., et al. Reverse electrical remodeling by cardiac resynchronization therapy: prevalence and clinical impact. J Cardiovasc Electrophysiol. 2012;23(11):1219–1227. doi: 10.1111/j.1540-8167.2012.02376.x. [DOI] [PubMed] [Google Scholar]
- 5.Nguyen U.C., Verzaal N.J., Nieuwenhoven F.A.V., et al. Pathobiology of cardiac dyssynchrony and resynchronization therapy. Europace. 2018;20(12):1898–1909. doi: 10.1093/europace/euy035. [DOI] [PubMed] [Google Scholar]
- 6.Sharmohammadi M., Luo H., Westphal P., et al. Hemodynamics-driven mathematical model of first and second heart sound generation. PloS Comput Biol. 2021;17(9) doi: 10.1371/journal.pcbi.1009361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Lopes C., Pereira T., Barra S. Cardiac resynchronization therapy in patients with atrial fibrillation: a meta-analysis. Rev Port Cardiol. 2014;33(11):717–725. doi: 10.1016/j.repc.2014.05.008. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Baseline Transthoracic Echocardiography
(A) Apical 4-chamber view demonstrating severely reduced left ventricular systolic function with mechanical dyssynchrony. (B) Color Doppler imaging demonstrating severe nonischemic functional mitral regurgitation.
Transthoracic Echocardiography After Pulsed-Field Ablation
(A) Apical 4-chamber view obtained after restoration of sinus rhythm, demonstrating persistent left ventricular mechanical dyssynchrony associated with complete left bundle branch block. (B) Color Doppler imaging demonstrating residual moderate functional mitral regurgitation.
Transthoracic Echocardiography 5 Days After CRT Pacemaker Implantation
(A) Apical 4-chamber view demonstrating improvement in left ventricular ejection fraction (44%) and reduction of left ventricular mechanical dyssynchrony. (B) Color Doppler imaging demonstrating marked reduction of mitral regurgitation.
Transthoracic Echocardiography 1 Month After CRT Pacemaker Implantation
Apical 4-chamber view demonstrating further improvement in left ventricular ejection fraction (52%) with marked reduction of left ventricular mechanical dyssynchrony.
Data Availability Statement
The data underlying this article are not publicly available given patient confidentiality but may be available from the corresponding author upon reasonable request and with appropriate institutional approval.