Dilated cardiomyopathy is a heart disease consisting of dilatation of the left ventricular cavity, or of both ventricles, which is accompanied by systolic ventricular dysfunction and can be the consequence of various genetic predispositions and/or environmental noxae.1 The high prevalence and incidence of left bundle branch block (LBBB) in this group of patients (30% of cases),2 contrasts sharply with the 1% prevalence observed in the general population. Moreover, the prevalence increases progressively with age, reaching 3% in patients older than 80 years, often related to underlying structural heart disease.3,4 These observations reinforce the idea that LBBB could be an acquired disorder due to conduction disturbances that appear during the natural course of the disease. However, a small subgroup of patients with a long-standing history of LBBB and no evidence of structural heart disease at diagnosis have been described, who have progressive deterioration of ventricular function with marked intraventricular asynchrony during follow-up, and who are hyperresponsive to cardiac resynchronization therapies (CRT). This could suggest the existence of a distinct clinical entity in which electromechanical desynchrony caused by LBBB is the cause and not the consequence of the cardiomyopathy,5–8 known as LBBB-induced cardiomyopathy (LBBB-ICMP).

Current recommendations indicate that medical therapy is the cornerstone for HF patients with left ventricular ejection fraction (LVEF) <40% and suggest starting with a combination of beta-blockers, mineralocorticoid receptor antagonists, angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitors (ARNI). Recently, SGLT2 inhibitors have been added to this therapeutic strategy. However, there is little evidence of the effect of these drugs in patients with LBBB-ICMP, although it seems that their response would be worse than in patients with narrow QRS.9 In contrast, several retrospective studies have analyzed the response of patients with LBBB-ICMP to CRT and physiological pacing (His pacing or LBBB) in which, after correction of the asynchrony generated by LBBB,10 almost all patients improved their functional class and recovered normal LVEF, even with proven long-term prognostic benefits.5,11

In this context, the main objective of this study was to evaluate the effect on LVEF of new guideline-directed medical therapy (GDMT) for patients with HF and reduced LVEF in patients with LBBB-ICMP.

This retrospective analysis included all patients with LBBB-ICMP who were admitted for an episode of HF and/or who were assessed for de novo ventricular dysfunction in the outpatient HF unit of the University Hospital of Santiago de Compostela between 2020 and 2021.

The inclusion criteria were: a) history of LBBB for at least 2 years with LVEF> 50% at diagnosis; b) sinus rhythm; c) LVEF <40% at first assessment prior to initiation of medical treatment; d) admission for HF or New York Heart Association functional class ≥ 2; and e) absence of other identifiable causes of cardiomyopathy, including severe mitral or aortic valve disease. The exclusion criteria were: a) underage patients; b) loss to follow-up during the process of drug titration; and c) loss of patient LVEF information at baseline or at the end of the study period.

Outpatient follow-up of patients after hospital discharge or after the first assessment consultation was done by dedicated personnel from the HF unit. Medical staff and specialized nursing staff were responsible for monitoring clinical events and titration of neurohormonal treatment in accordance with clinical practice guidelines until the maximum target doses of each drug or the maximum dose tolerated by the patient were reached.

The etiological study of the cardiomyopathy was carried out by specialist cardiologists and the tools used to complete the study included information from the clinical history, analytical parameters, electrocardiograms, transthoracic echocardiography, cardiac magnetic resonance imaging and coronary angiography, among others.

The electrocardiographic criteria used to diagnose LBBB were QRS duration> 130ms, absence of Q wave in leads I, V5 and V6, monomorphic R wave in I, V5 and V6 and ST-segment shift and T wave with opposite direction to the main deviation of the QRS complex12 and were reviewed one by one by an electrophysiologist (MRM).

LVEF was assessed at baseline and at the end of drug titration using Simpson's biplane method measured by transthoracic echocardiography or by cardiac magnetic resonance (CMR) in those patients with a suboptimal acoustic window for adequate quantification of ventricular volumes. This procedure is routinely performed in our institution at 3 months after the first medical contact to evaluate the referral for CRT/physiological pacing.

Information on personal history and comorbidities was obtained from the electronic medical records of each patient. The analytical parameters recorded were those obtained from the blood test performed for the first consultation.

All patients are part of a registry whose protocol has been approved by the ethics committee of our hospital. Informed consent was collected from patients participating in the study.

From January 2020 to December 2021, a total of 1497 patients were evaluated in the outpatient HF department. Of these, 854 patients had QRS <130ms, 314 LBBB, 162 pacemaker rhythm and 168 wide QRS non-LBBB. Only 21 patients with LBBB met the inclusion criteria for the study, of whom the initial event was an admission for HF in 10 (figure 1). The baseline and analytical characteristics, as well as the percentage of patients treated with each of the medications analyzed are shown in table 1.

Figure 1.

Flow chart of patients included in the study cohort. EGC, electrocardiogram; LBBB, left bundle branch block, LVEF, left ventricular ejection fraction.

(0.7MB).

To complete the etiological study, at least 1 transthoracic echocardiogram was performed in all patients, while coronary angiography was performed in 4 patients, with no evidence of significant coronary lesions in any of them. CMR was performed in 19 patients, of whom 11 had no late gadolinium enhancement (LGE); 6 had LGE in the basal right ventricle insertion (nonspecific finding), and 1 had an intramyocardial septal pattern and in both right ventricle septal insertions.

The mean time from first diagnosis of LBBB to first consultation was 4.05±4.1 years. The mean QRS duration at the first consultation was 163.7±17.2ms, with an axis of −3.6° and a mean QTc duration of 478.7ms. There was a trend toward a decreased response to pharmacological treatment in patients with a longer QRS, although this did not reach statistical significance (r=−0.4128; P=.07) (figure 2).

Figure 2.

Correlation between QRS duration and change in left ventricular ejection fraction after drug titration.

(0.09MB).

After a median follow-up time of 8.3 [7.0-14.3] months, there was a reduction in N-terminal pro-B-type natriuretic peptide levels from the first consultation from a median of 1081 [651.5-2619] pg/mL to 383 [169-1084] pg/mL (P=.027). However, this did not lead to a significant change in NYHA class (1.91±0.46 at baseline vs 1.81±0.53 at the end of titration; P=.542). The absolute improvement in LVEF was 3.12±2.27% (29.5±5.7% to 32.7%±8.5%; P=.172) and the mean reduction in left ventricular end-diastolic volume was 17.5±39.9mL (189.5±69.7mL to 172.0±43.7mL; P=.055). No patient achieved LVEF normalization (LVEF> 50%), 2 remained stable, and 3 patients showed worse LVEF (figure 3). A secondary multivariate analysis was conducted, including LVEF and end-diastolic volume at baseline follow-up, medical treatment, and duration of medical treatment; pretreatment LVEF and duration of pharmacological titration were not significantly associated with improvement in LVEF (−0.52% per 1% increase in pretreatment LVEF (95% confidence interval, −1.64 to +0.60; P=.323) and −0.41% for each month of follow-up (95% confidence interval, −1.90 to +1.08; P=.548)).

Figure 3.

Central Illustration. Change in patients’ LVEF after pharmacologic titration to guideline-directed medical therapy and percentage of patients treated with each drug. ACEI, angiotensin-converting enzyme inhibitors; ARNI, angiotensin receptor-neprilysin inhibitors; BB, beta-blockers; HF, heart failure; IQR, interquartile range; LBBB-ICMP, left bundle branch block-induced cardiomyopathy; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonists; NYHA, New York Heart Association; SCD, sudden cardiac death.

(0.29MB).

During follow-up, 2 patients were admitted to hospital for decompensated HF. One patient was admitted during the titration period and the second several months after the end of this period in the setting of atrial fibrillation with rapid ventricular response and was referred for catheter ablation.

After pharmacological titration, 7 patients (33.3%) were implanted with a CRT-defibrillator device and 1 patient (4.8%) underwent CRT device implantation. All procedures were successful and there were no complications during device implantation. Only 1 patient developed pacemaker wound infection in the months following implantation. In the remaining patients, 2 refused device implantation, 3 were pending decision, 3 were not candidates due to comorbidities, 3 did not meet the criteria for CRT due to LVEF> 40%, 1 did not meet the criteria after improvement to NYHA functional class I, and 1 patient died suddenly before the decision was made.

After a median of 8.7 [5.9-9.4] months after CRT device implantation, the observed improvement in mean LVEF in the device implanted group was 18.1±6.4% (P=.003) (figure 4) and the reduction in end-diastolic volume was 37.4±23.7mL (P=.003).

Figure 4.

Change in patients’ LVEF after cardiac resynchronization device implantation. CRT, cardiac resynchronization therapy; LVEF, left ventricular ejection fraction.

(0.11MB).

Our study highlights the likely poor response to optimal GDMT among patients with de novo ventricular dysfunction secondary to asynchrony produced by long-standing advanced LBBB. No significant improvement in functional class, end-diastolic volume or LVEF was observed in patients after pharmacological titration. In fact, no patient recovered LVEF after pharmacological titration and 3 patients experienced worsening of LVEF at the end of the process. Importantly, sudden cardiac death occurred in 1 patient during the titration period. On the other hand, there was a significant improvement in LVEF and reduction in end-diastolic volume in patients who were redirected to CRT.

GDMT including BB, mineralocorticoid receptor antagonists, ACEI/angiotensin receptor blocker/ARNI±SGLT2 inhibitors seems to be ineffective in improving LVEF and functional class in patients with de novo HF and LBBB-ICMP. CRT may perform better in improving and recovering LVEF than GDMT in patients with LBBB-ICMP, and therefore consideration of early CRT implantation could be a reasonable strategy in this subset of patients.

None.

All authors included in the study have been involved in the design, collection or analysis and interpretation of the data, writing of the text or final revision of the presented text.

This research has not received any specific grant from any public, commercial, or not-for-profit sector. The authors declare that there is no conflict of interest.