{'fraction_non_alphanumeric': 0.026441541892322395, 'fraction_numerical': 0.00414144632048423, 'mean_word_length': 5.216831683168317, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Upgrade of cardiac resynchronization therapy by utilizing additional His-bundle pacing in a patient with lamin A/C cardiomyopathy: an autopsy case report


 
 
 A number of heart failure patients (HF) do not fully benefit from cardiac resynchronization therapy (CRT). Although His bundle pacing (HBP) have been developed as an alternative strategy, its role for treating advanced cardiomyopathy remains unclear.
 
 
 
 We previously reported a patient with lamin A/C cardiomyopathy (Eur Heart J Case Rep. 2020; 4:1-9). He had turned non-response to conventional biventricular pacing (BVP), and an upgrade to CRT combining para-His bundle pacing (HBP) and left ventricular (LV) pacing had markedly improved his HF status. In the present report, we assessed the autopsy and histological findings of this patient. A histological examination of both the LV and right ventricular (RV) apex pacing regions exhibited extensive scarring. Although a distinct conduction system was not identified in the alternative para-HBP region, the RV endocardium had more viable myocytes in this region.
 
 
 
 In patients with advanced cardiomyopathy accompanied by extensive fibrosis, RV apex pacing, delivered from scar tissue, can render conventional BVP ineffective. Additionally, HBP alone can not provide adequate resynchronization under the presence of diffuse injury of the His-Purkinje system. In these circumstances, combined para-HB and LV pacing may facilitate electrical and mechanical resynchronization of the ventricles and may be attributed to favourable CRT response in advanced HF, even if para-HBP fails to directly capture the conduction system.


Our previous case series showed that an upgrade from conventional cardiac resynchronization therapy (CRT) to CRT combining para-His-bundle pacing (HBP) and left ventricular pacing (LVP) significantly improved the heart failure (HF) status in patients with advanced cardiomyopathy. 1 To continue that report, we provide the autopsy findings and histological examinations of patient No. 1 with lamin A/C gene (LMNA) cardiomyopathy.
A year after the upgrade, he developed renal failure and died from hyperkalaemia resistant to dialysis. An autopsy revealed an enlarged and dilated heart, weighing 560 g ( Figure 1A). Microscopic examination with Masson trichrome staining of the LVP site showed a partially scarred region (blue cytoplasm) ( Figure 1B), whereas extensive scarring was present in the region of the right ventricular (RV) apex pacing lead ( Figure 1C). The alternative pacing lead was located below the septal tricuspid leaflet and 4 mm from the lower edge of the membranous septum ( Figure 1D). Microscopic examination showed diffuse interstitial fibrosis showed extensive interstitial fibrosis with a partial scar region (blue cytoplasm). (C) Histological examination at the right ventricle apex pacing region. Myocytes were present over an extensive region of scarring. (D) Close-up view of the alternative pacing lead, located below the septal tricuspid leaflet and 4 mm away from the lower edge of the membranous septum transilluminated from the left ventricle. (E) Microscopic examination showed interstitial fibrosis diffusely present throughout the myocardium with a scar in the mid-layer. However, some more viable myocardium (red cytoplasm) was present within the right ventricle septal endocardium compared to that in the right ventricle apex pacing region. Although the right bundle branch was assumed to run superficially in this region, it was difficult to identify distinct conduction systems microscopically. and a scarred region within the middle layer. However, viable myocardium (red cytoplasm) was present within the RV endocardium ( Figure 1E). Although this region was presumably where the right bundle branch (RBB) ran superficially, it was difficult to identify a distinct conduction system microscopically.
The histological sections at the level of the interventricular component of the membranous septum, which was attached inferiorly to the crest to the muscular interventricular septum (IVS), showed extensive scarring. A conduction system, i.e., His-bundle, left bundle branch, and RBB, could not be identified ( Figure 1F).
The European Society of Cardiology statements consider HBP to be safe as an alternative technique to CRT. 2 However, HBP may not provide adequate resynchronization for patients with advanced cardiomyopathy due to coexisting scarred myocardium or intraventricular conduction defect. 3 The most advanced cardiomyopathy is accompanied by extensive fibrosis and is associated with adverse clinical outcomes. 4 Avoiding scarred areas pacing is critical since nonviable tissue can no longer be resynchronized. 5 In the present case, scar formation was evident around the left ventricle and right ventricle apex pacing sites. No studies have so far evaluated the importance of myocardial substrate and remodelling for RV lead placement. This autopsy study focused on whether the alternative pacing lead had actually captured the conduction system. We had speculated that the upgraded CRT improved the patient's HF status because it successfully captured the conduction system with the alternative pacing lead. However, we did not recognize any distinct conduction system in the para-HBP region. This suggested that para-HBP would actually fail to recruit, directly or partially, the intrinsic conduction system for resynchronization. Extensive scarring in the basal IVS is known to be a characteristic of LMNA cardiomyopathy. 6,7 Aiming for selective HBP may not always be an appropriate choice when performing CRT in patients with advanced cardiomyopathy with IVS scarring and a damaged His-Purkinje system. We hope that these autopsy findings can help solve another puzzle in understanding the non-response to CRT. Further studies should be encouraged to evaluate RV myocardial substrate in advanced cardiomyopathy patients requiring CRT.

Consent
The authors confirm that written consent for submission and publication of this case series including images and associated text has been obtained from the patients in line with COPE guidance.

Funding
This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.