Rate-Related Left Bundle Branch Block-Induced Cardiomyopathy

Introduction

Rate-related left bundle branch block (RR-LBBB) is the most common cause of episodic or transient LBBB but can be the most elusive etiology of LBBB-induced cardiomyopathy (LBBB-CM). In this article, we present a case of a patient with non-ischemic cardiomyopathy (NICM) implanted with a cardiac resynchronization therapy-defibrillator (CRT-D) who was diagnosed with rate-related LBBB-induced CM (RR-LBBB-CM) after extraction of his device. We also review the different causes of episodic LBBB, LBBB-CM, and its response to CRT, as well as offer insights about appropriate monitoring and workup for patients diagnosed with RR-LBBB-CM.

Background

The prevalence of left bundle branch block (LBBB) in the general population is <1%; this increases with age, and is usually associated with concomitant structural heart disease (SHD) such as coronary artery disease (CAD) or cardiomyopathy (CM).¹ In comparison, the prevalence of LBBB without SHD is even lower (0.1%) and, in conjunction with left ventricular (LV) dysfunction, it is oftentimes difficult to discern whether the LBBB is a result of the CM or vice versa.² LBBB-induced cardiomyopathy is often overlooked as an etiology of non-ischemic cardiomyopathy, but is important to recognize for the appropriate treatment of a patient. The electrical and resultant mechanical dyssynchrony induced by the abnormal conduction over the left bundle can lead to myocardial remodeling and subsequent LV dysfunction.³

More elusive than a permanent LBBB is a transient LBBB. There are numerous etiologies leading to transient LBBB that have been reported in the literature, the most common being a rate-dependent or rate-related LBBB.⁴ The described electrophysiologic mechanisms of a RR-LBBB include phase 3 and 4 block, acceleration-dependent block, and concealed retrograde conduction of the left bundle.⁵ Data on the prevalence and impact of RR-LBBB, specifically at heart rates within the normal range, in the development of NICM is unknown and is limited to case reports.

Case Description

A 61-year-old male with a history of hypertension, LBBB, and NICM (LV ejection fraction [EF] 30%) status post implantation of a CRT-D device was transferred to our institution for extraction of his cardiac device. Initial indications for CRT-D implant were EF <35%, LBBB with QRS >150 ms, and New York Heart Association Class 3 heart failure. ECG prior to CRT-D implantation is shown in Figure 1. About a year and a half after initial implant, the patient noticed that the device was gradually migrating laterally towards the left axilla, causing significant pain and discomfort. He underwent pocket revision and was discharged on oral antibiotics. The patient returned the next day due to severe bleeding from the incision site with associated swelling and pain. He was started on a 5-day course of intravenous antibiotics and then transferred to our hospital for extraction, as the generator had partially externalized through the incision. The patient was hemodynamically stable and afebrile. White blood cell count was within normal limits and initial blood cultures were negative for any growth. 

Figure 2A shows the presenting ECG, which demonstrates normal sinus rhythm with biventricular pacing. The patient underwent uneventful extraction of his CRT-D system. Post-operative day (POD) 1, the patient underwent transthoracic echocardiogram (TTE), which demonstrated a normal EF of 70%. Temporal changes in the electrocardiographic abnormalities are shown in Figures 2B and 2C. Despite a sinus rate of only 4 beats per minute faster, the patient developed a LBBB that continued to be present at a heart rate of 70 bpm or more but would disappear below 70 bpm. Wound culture taken from the pocket during extraction grew Enterobacter cloacae, so he was transitioned to oral antibiotics and discharged on POD 2. 

In summary, the patient was implanted with a CRT-D given his diagnosis of NICM and associated LBBB; however, after necessary removal of the cardiac device, he was found to have complete resolution of his CM as well as the LBBB, demonstrating a diagnosis of RR-LBBB-CM.

Discussion

We present this case to discuss rate-related left bundle branch block-induced cardiomyopathy, which was only diagnosed after CRT-D extraction. A RR-LBBB can be difficult to diagnose, particularly if the patient’s heart rate is above that at which the LBBB appears (known as the critical heart rate) at the time of ECG or Holter monitoring. We also determine its contribution to the development of LV dysfunction.

Rate-Related LBBB

There are numerous etiologies of transient LBBB, rate-related LBBB being the most common (see Table 1 for a compiled list of causes of transient LBBB). RR-LBBB can be tachycardia- or bradycardia-dependent. The described electrophysiologic mechanisms of a RR-LBBB include physiologic block during phase 3 of the action potential, acceleration-dependent block above the critical heart rate, phase 4 bradycardia-dependent block due to disease in the His-Purkinje system, and transseptal, retrograde, concealed invasion of the left bundle rendering it refractory to subsequent depolarizations.⁵ Unless the onset at which the LBBB occurs is recorded, it can be difficult to determine the exact mechanism.

Most of the published literature focuses on RR-LBBB as a result of an increase in heart rate secondary to exercise. The prevalence of exercise-induced LBBB (EI-LBBB) in patients undergoing exercise testing is approximately 0.38%, and the critical heart rate is directly dependent on the rate of change in the cycle length.^4,6 It has also been demonstrated that the rate at which an EI-LBBB occurs can be an important prognostic factor. EI-LBBB occurring at rates <120 bpm portends a worse prognosis and usually correlates with the presence of CAD, while appearance of a LBBB at rates >120 bpm is associated with normal coronaries and has a better prognosis.⁷ 

The critical heart rate at which a LBBB can appear varies greatly from patient to patient and can be associated with underlying comorbidities such as CAD. Seibolt at al performed an extensive literature review of reported cases of RR-LBBB from 1948-2018.⁵ Based on their review of 54 patients, the critical rate at which a LBBB appeared (58-210 bpm; average 107.2 ± 35.1 bpm; median 100 bpm) was significantly faster than the critical rate at which it disappeared (50-193 bpm; average 89.2 ± 33.4 bpm; median 80 bpm). In addition, about half (46%) of the patients developed a LBBB at a heart rate in the normal sinus range (60-99 bpm), as did our patient at 70 bpm. Unfortunately, data regarding the presence or absence of LV dysfunction was not reported.

CRT for LBBB-CM

Evidence demonstrating the negative effects of a LBBB as it relates to electrical and mechanical LV dyssynchrony in both animal⁸ and human⁹ models is quite clear; however, the duration of time required for the LBBB to be present in order to cause LV dysfunction is unknown and varies among published data. In a study by Vaillant et al,³ they reported a series of six patients with a documented history of LBBB for at least 5 years. The time from diagnosis of LBBB to overt heart failure and CRT-D implantation ranged from 5 to 22 years. In addition, all patients responded to CRT with recovery of their EF and improvement in symptoms, demonstrating that LBBB-CM can be a slow but potentially reversible process. In a review by Sanna et al, a detailed algorithm for diagnosing LBBB-CM is presented and they propose an early strategy for CRT-D implantation with emphasis that the diagnosis is usually retrospective.¹⁰ Isnard and Pousset comment in an editorial to this work that a “hyper-response” to CRT-D could lend another clue in the post-hoc diagnosis of LBBB-CM.¹¹ It has also been demonstrated that if CRT cannot be attained via the traditional placement of a coronary sinus lead, His bundle and left bundle branch pacing are acceptable alternatives and can reverse LBBB-CM.^12,13

CRT for EI-LBBB

Unfortunately, there is limited evidence for the benefit of CRT-D in EI-LBBB, which is limited to case reports. Two separate reports describe patients with severe shortness of breath¹⁴ or acute heart failure¹⁵ induced by EI-LBBB and refractory to medical therapies, but which improved significantly after implantation of CRT. Similarly, Scolari et al reported a case of a 57-year-old female undergoing heart transplantation evaluation due to severe LV dysfunction, but was found to have EI-LBBB during cardiopulmonary stress testing.¹⁶ She was deemed not to be a transplant candidate, and was instead implanted with CRT and showed a marked improvement in her symptoms and EF.

CRT for LBBB-CM at Normal Sinus Heart Rates

Despite the overwhelming evidence for the benefit of CRT in LBBB-CM and the few anecdotal case reports of CRT in EI-LBBB, there are not sufficient data or recommendations in regards to CRT for RR-LBBB at “normal” heart rates (ie, 60-99 bpm). In a case report by Contractor et al, they describe a patient with NICM as a result of a RR-LBBB at a rate of 70 bpm.¹⁷ The patient was implanted with a cardiac device using three leads: an atrial lead, RV defibrillator lead, and His bundle lead. While the patient’s CM resolved with His bundle pacing, they were faced with elevated pacing thresholds (3.8V at 1 ms pulse width) and rapid battery depletion, inherent to that modality of pacing.

RR-LBBB-CM

While the concept of LBBB-CM is well established, the incidence, evolution over time, and predisposing factors of RR-LBBB-CM are not known. In addition, the duration of time required for LBBB to be present in order to develop CM is unclear. Given the current state of knowledge and recommendations, CRT can be quite controversial. However, as these patients are at risk of developing LV dysfunction, it is reasonable to recommend close follow-up with routine echocardiography, especially if new symptoms of heart failure develop. Holter monitoring to assess the average rate at which LBBB appears as well as duration of time with LBBB throughout the day could also be a reasonable modality to guide management. In addition, maximum tolerated beta-blocker therapy, and if necessary, ivabradine, to achieve a heart rate below the critical rate should be implemented prior to recommending CRT.

Although we present this case as a diagnosis of RR-LBBB-CM, there could potentially be other explanations as to the resolution of the patient’s CM. For instance, the patient could have had a baseline LBBB as a result of his CM at the time of his initial CRT-D implantation, which subsequently resolved due to the resynchronization therapy and persisted even after the device was extracted. However, we do show that the patient’s LBBB was present above the presumed critical heart rate of approximately 70 bpm prior to CRT implantation, making RR-LBBB-CM a viable diagnosis. Nonetheless, further studies are required to help guide patient management for this elusive diagnosis.

Conclusion

RR-LBBB-CM is a rare entity and poses an extremely challenging scenario when it comes to patient management. Optimal medical therapy along with close monitoring and extensive workup should be performed to exclude all other causes of LBBB and CM before recommending treatment with CRT. 

Disclosures: The authors have no conflicts of interest to report regarding the content herein.

1. Auffret V, Martins R, Daubert C, et al. Idiopathic/iatrogenic left bundle branch block-induced reversible left ventricular dysfunction. J Am Coll Cardiol. 2018;72(24):3177-3188.
2. Fahy G, Pinski S, Miller D, et al. Natural history of isolated bundle branch block. Am J Cardiol. 1996;77:1185-1190.
3. Vaillant C, Martins R, Donal E, et al. Resolution of left bundle branch block-induced cardiomyopathy by cardiac resynchronization therapy. J Am Coll Cardiol. 2013;61:1089-1095.
4. Bazoukis G, Tsimos K, Korantzopoulos P. Episodic left bundle branch block – a comprehensive review of the literature. Ann Noninvasive Electrocardiol. 2016;21(2):117-125.
5. Seibolt L, Maestas C, Lazkani M, Fatima U, Loli A, Chesser M. Rate-related left bundle branch block and cardiac memory in a patient with bradycardia: case report and literature review. Clin Cardiol. 2018;41:1097-1102.
6. Stein R, Ho M, Oliveira C, et al. Exercise-induced left bundle branch block: prevalence and prognosis. Arq Bras Cardiol. 2011;97:26-32.
7. Hertzeanu H, Aron L, Shiner R, Kellermann J. Exercise dependent complete left bundle branch block. Eur Heart J. 1992;13:1447-1451.
8. Strik M, van Middendorp LB, Vernooy K. Animal models of dyssynchrony. J Cardiovasc Transl Res. 2012;5:135-145.
9. Sze E, Dunning A, Loring Z, et al. Comparison of incidence of left ventricular systolic dysfunction among patients with left bundle branch block versus those with normal QRS duration. Am J Cardiol. 2017;120:1990-1997.
10. Sanna G, Merlo M, Moccia E, et al. Left bundle branch block-induced cardiomyopathy: a diagnostic proposal for a poorly explored pathological entity. Int J Cardiol. 2020;299:199-205.
11. Isnard R, Pousset F. Left bundle branch block-induced cardiomyopathy: Myth or reality? Int J Cardiol. 2020;300:201-202.
12. Ajijola, O, Upadhyay G, Macias C, Shivkumar K, Tung R. Permanent His-bundle pacing for cardiac resynchronization therapy: initial feasibility study in lieu of left ventricular lead. Heart Rhythm. 2017;14:1353-1361.
13. Li Y, Chen K, Dai Y, et al. Recovery of complete left bundle branch block following heart failure improvement by left bundle branch pacing in a patient. J Cardiovasc Electrophysiol. 2019;30(9):1714-1717.
14. Prystowsky EN, Padanilam BJ. Cardiac resynchronization therapy reverses severe dyspnea associated with acceleration-dependent left bundle branch block in a patient with structurally normal heart. J Cardiovasc Electrophysiol. 2019;30(4):517-519.
15. Zeppenfeld K, Schalij MJ, Bleeker GB, Holman ER, Bax JJ. Acceleration-dependent left bundle branch block with severe left ventricular dyssynchrony results in acute heart failure: are there more patients who benefit from cardiac biventricular pacing? J Cardiovasc Electrophysiol. 2006;17:101-103.
16. Scolari F, Silveira A, Menegazzo W, et al. Expanding benefits from cardiac resynchronization therapy to exercise-induced left bundle branch block in advanced heart failure. ESC Heart Fail. 2020;7:329-333.
17. Contractor T, Timothy P, Pai S, Mitchell I, Bhardwaj R, Mandapati R. Cardiac resynchronization therapy for rate-related bundle branch block: is there a role for His-bundle pacing? HeartRhythm Case Rep. 2018;4:475-479.
18. Vasheghani-Farahani A, Tajdini M, Mohsenizadeh SA, Hosseini SMR. Reversible left bundle branch block should be mentioned in cardiac resynchronization therapy: a clinical case report. ARYA Atheroscler. 2016;12(3):153-155.