Left bundle branch block: from cardiac mechanics to clinical and diagnostic challenges

Authors, Journal, Affiliations, Type, DOI

• Elena Surkova, Luigi P. Badano, Roberto Bellu, Patrizia Aruta, Federica Sambugaro, Gabriella Romeo, Federico Migliore, Denisa Muraru
• Europace 2017;19(8):1251–1271
• Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Italy
• Review article
• DOI: 10.1093/europace/eux061

Overview

A comprehensive Europace review synthesizing LBBB epidemiology, aetiology, ECG diagnosis, pathophysiological consequences of asynchronous electrical activation, multimodality imaging findings, and clinical management. The review integrates recent data on connexin genetics, TAVR-induced LBBB, novel echocardiographic parameters (septal flash, apical rocking, systolic stretch index, LV pressure-strain loops), stress testing pitfalls, and Sgarbossa criteria performance. The central message is that LBBB has evolved from a simple ECG pattern to a multidimensional clinical entity requiring imaging-guided management beyond ECG criteria alone.

Keywords

Left bundle branch block; Electrocardiography; Cardiovascular imaging; Left ventricular remodelling; Prognosis

Key Takeaways

Epidemiology and Aetiology

• Prevalence 0.1–0.8% in asymptomatic adults including athletes; almost never occurs before age 35, suggesting an acquired condition
• Prevalence increases from <1% at age 50 to 6% by age 80; mean age at LBBB diagnosis 70±10 years (men), 68±11 years (women)
• Associated factors: hypertension, CAD, valvular heart disease, cardiomyopathies, myocarditis, LVH, ST-T changes; develops without identifiable risk factors in some individuals
• Genetics: Variants in connexin 40 (atria, proximal conduction system) and connexin 43 (Purkinje cells and cardiomyocytes — GJA1 locus) are associated with cardiomyopathy and can cause LBBB; 22 GWAS loci identified for QRS duration
• Connexin 43 downregulated in end-stage HF → increased ventricular arrhythmia risk; ischaemia → connexin 43 dephosphorylation → intracellular translocation → reduced intraventricular conduction

TAVR-Induced LBBB

• Incidence varies widely 7–83% depending on device; systematic review: 14.0% (4.0–30.2%) for Sapien vs 45.2% (22.0–65.0%) for CoreValve
• Mechanism: proximity of AV node and left bundle branch to aortic valve; mechanical interaction of valve frame with conduction system
• Predictors of new-onset LBBB after TAVR: device geometry, baseline QRS duration, pre-procedural RBBB, male gender, prior MI, prior CABG, depth of implantation
• Dutch registry (CoreValve + Sapien): All-cause mortality significantly higher in TAVR-LBBB vs no-LBBB (37.8% vs 24.0%; P=0.002); device type had no impact on mortality of TAVR-induced LBBB; iatrogenic LBBB was the strongest independent predictor of mortality
• PARTNER trial subanalysis (Edwards Sapien only; patients with baseline conduction abnormalities excluded): TAVR-induced LBBB was NOT associated with 1-year all-cause mortality, cardiovascular mortality, hospitalization, stroke, or MI — only associated with increased pacemaker implantation
• Conflicting results explained by differences in baseline characteristics, timing of LBBB determination (transient vs persistent cases), and inclusion of pacemaker patients in the LBBB group (which reduces expected bradyarrhythmic SCD)
• Post-TAVR LBBB associated with decrease in LVEF (vs increase without LBBB); persistent LBBB after surgical AVR is rare (<2%), much lower than TAVR rates

ECG Criteria

• Conventional (AHA/ACCF/HRS 2009): QRS ≥120ms + notched/slurred R in I, aVL, V5-V6 + absent Q in I, V5-V6 + VAT >60ms in V5-V6; original dog-model criteria from 1941 extrapolated to humans

• 30% of patients meeting conventional ECG criteria do not have significant R-L ventricular activation delay by endocardial mapping — conventional criteria have limited specificity for true LBBB

• Strauss strict criteria: QRS ≥140ms (men) / ≥130ms (women) + mid-QRS notching/slurring; higher QRS cut-off for men reflects larger heart size; CMR tagging: Strauss patients had longer septal-to-lateral peak circumferential strain delay (210±137ms vs 122±102ms; P=0.045)
• Strauss criteria show better echocardiographic CRT response and higher event-free survival (Mascioli 2012, Garcia-Seara 2018) but independent association with outcomes disappears after adjustment for aetiology and QRS duration (Bertaglia 2017)
• Rate-dependent LBBB: phase-3 block during tachycardia; phase-4 spontaneous depolarization at slower rates

Prognosis of LBBB

• LBBB associated with increased cardiovascular mortality, SCD, and HF vs normal conduction and vs RBBB; Framingham study: half of cardiovascular deaths occurred in LBBB subjects
• 3983-subject, 29-year longitudinal study: LBBB associated with increased cardiovascular morbidity/mortality; SCD often the first manifestation in those with LBBB; patients developing LBBB <45 years without risk factors had better prognosis than those ≥50 years with risk factors
• Prolonged QRS ≥110ms (any morphology): associated with all-cause and cardiac mortality and sudden arrhythmic death in large middle-aged cohort; LBBB morphology separately predicted only sudden arrhythmic death
• In HF with LVEF ≤39%: LBBB and other IVCDs (including RBBB) are equally strong independent predictors of mortality in all age groups
• TAVR-induced LBBB prognosis: conflicting data (see TAVR section above)

Pathophysiological Consequences of Asynchronous Activation

• Block in Purkinje system → cell-to-cell myocardial conduction (not specialized tissue) → prolonged time for LV activation → mechanical dyssynchrony; RV free wall + IVS contract before LV lateral wall
• Active RV + IVS forces at early systole are unopposed by LV lateral regions → RV contraction applies force on IVS through attachment points → IVS hinges leftward and flattens, displacing blood toward lateral wall
• Early IVS contraction closes mitral valve and terminates LV filling without relevant LV pressure rise (contracting volume too small); prestretch of lateral wall → powerful late contraction; enables LV ejection to start and causes force imbalance — IVS curves back into RV with rebound stretch during early LV ejection
• Lateral wall hypertrophy from doing most of LV ejection work; reduced septal blood flow and relative lateral hyperperfusion (two mechanisms: altered autoregulation, impaired diastolic coronary flow via septal perforator compression)
• Long-term animal model: LV dilation, asymmetric hypertrophy, decreased pump function, altered Ca²⁺ transport, pro-arrhythmic state
• Functional mitral regurgitation from mitral annular dilation and dyssynchronous papillary muscle contraction → begets more LV dilation → HF resistant to conventional therapy

Echocardiographic Features — Classic Patterns

• Septal flash (SF): Early rapid leftward IVS motion (septal beak) before or early during ejection, followed by rightward paradoxical motion; driven primarily by early RV free wall contraction pulling IVS leftward (NOT active IVS contraction) — simulation data; amplitude modulated by diastolic ventricular pressures
• SF ≠ Septal systolic rebound stretch: Septal systolic rebound stretch (strain echo) is a separate phenomenon dependent on late LV lateral wall contraction forces; the two terms are not interchangeable
• Apical rocking: Back-and-forth apex motion — initial apical motion toward septum (early IVS contraction), then lateral motion during ejection (late lateral wall contraction); highly specific for LBBB-induced dyssynchrony
• Both SF and apical rocking are CRT predictors: patients with SF/apical rocking before CRT had better outcomes and long-term survival; correction of both by CRT was associated with LV reverse remodeling
• SF alone: 8.4% of patients; apical rocking alone: 8.6% — each can occur independently; scar tissue in septum/anteroseptum affects presence of both
• Lateral wall hypertrophy; shorter LV filling/ejection time intervals; longer isovolumic time (delayed lateral wall contraction → late aortic valve opening)
• SF differential: ischaemic dyskinesis/aneurysm; other conduction abnormalities (pacing, VPC, WPW); post-cardiac surgery; RV pressure/volume overload; pericardial disease; abnormal IVS motion from conduction disorder = preserved (but delayed) septal thickening vs reduced/absent thickening in ischaemia/injury

Echocardiographic Features — Novel Parameters

• 2D speckle-tracking longitudinal strain: Typical LBBB pattern = first IVS peak shortening within first 70% of ejection, followed by late lateral wall peak shortening after aortic valve closure; absence of this pattern = unfavorable long-term outcome after CRT and increased risk of death/LVAD/transplant
• 1/3 of LBBB patients selected for CRT do not have the typical speckle-tracking contraction pattern; mismatch between ECG and LV mechanics independently associated with adverse outcomes
• Apical rocking observed in 26% and SF in 20% of CRT patients without typical LBBB on ECG, most of whom responded to CRT — LV mechanics may select CRT candidates independent of ECG morphology
• Systolic stretch index (SSI): Quantitative parameter from 2D speckle-tracking radial strain (mid-LV short-axis view); sum of posterior-lateral systolic prestretch at pre-ejection + septal systolic rebound stretch; SSI >9.7% was independently associated with more favorable clinical outcomes after CRT even in patients with intermediate QRS duration (120–149ms)
• LV pressure-strain loop area (myocardial work): Non-invasive quantification of regional myocardial work; septum in LBBB + chronic HF performs net negative work (systolic lengthening); after CRT, proportion of positive septal work increases dramatically
• Echographic particle image velocimetry: Tracks microbubbles to assess intraventricular fluid dynamics; CRT responders show longitudinal (base-apex) alignment of hemodynamic forces; non-responders develop transversal flow-mediated forces

Nuclear Imaging in LBBB

• Typical pattern: relative reduction of septal coronary flow + lateral hyperperfusion — two mechanisms (altered autoregulation; impaired diastolic coronary flow via septal perforator compression)
• Partial-volume effect (reduced IVS thickening + increased lateral thickening) may mimic perfusion heterogeneity on SPECT/PET → interpret with caution
• ECG-gated SPECT at end-diastole: more accurate for identifying CAD in LBBB
• True positive perfusion defects in LBBB: (i) reversible perfusion defects especially at end-diastole; (ii) concomitant apical defect; (iii) systolic dysfunction matching the perfusion defect

Diagnostic Challenges — Stress Testing

• Vasodilator stress preferred over exercise or dobutamine in LBBB — most pathophysiological effects causing false-positive results are due to increased inotropy/chronotropy
• Stress echocardiography: range of specificity 64% to >90% (experienced hands); better than SPECT for left coronary territory in experienced labs
• Meta-analysis (66 studies, 2203 patients): Exercise ECG sensitivity 83.4%, myocardial perfusion imaging sensitivity 82.1%; stress echocardiography highest specificity (88.7%) and accuracy (84.4%); exercise ECG lowest accuracy (66.4%)
• Myocardial contrast echocardiography with vasodilators: excellent diagnostic accuracy for CAD in LBBB (does not rely on wall thickening/endocardial displacement)
• Stress CMR: promising but limited evidence, high cost, device contraindications
• Dobutamine stress CMR superior to dobutamine stress echo for detecting new wall motion abnormalities in LBBB (single study)

Diagnostic Challenges — Sgarbossa Criteria for MI in LBBB

• Sgarbossa criteria most widely used for acute MI diagnosis in LBBB; concordant STE ≥1mm receives highest score (5 points); discordant STE ≥5mm receives lowest score (2 points)
• Meta-analysis of 10 studies: total Sgarbossa score ≥3 → sensitivity 20% (95% CI 18–23%), specificity 98% (95% CI 97–99%)
• High specificity but very low sensitivity — significant proportion of true STEMI in LBBB will be missed; ECG criteria alone insufficient; point-of-care troponin at 1–2 hours recommended
• Modifications proposed: Selvester criterion (standard STEMI threshold + 10% × (S amplitude − R amplitude)); Smith modification (25% of preceding S wave magnitude for discordant STE); Philips QRS area criterion (QRS area instead of amplitude)

Clinical Management and CRT

• No specific management guidelines for LBBB patients except those who develop HF + severe LV systolic dysfunction requiring CRT
• Class I CRT indication: LBBB + QRS ≥120ms + EF ≤35% + NYHA II–IV despite adequate OMT (level A for QRS >150ms, level B for 120–150ms)
• 30% CRT non-responder rate; multimodality imaging approach expected to improve CRT candidate selection
• Additional factors for CRT response prediction: site of latest mechanical activation, extent and location of myocardial scar, LV lead positioning, venous anatomy
• Novel approaches: redistribution analysis of coronary flow and perfusion/metabolism (CRT promotes homogeneity in myocardial perfusion); LV contraction pattern analysis; workload and energy loss analysis; intraventricular fluid dynamics

Limitations of the Document

• Review article without meta-analytic synthesis of primary trial data; conclusions based on author interpretation of the literature
• Multiple sections rely on single studies or small cohorts (e.g., dobutamine stress CMR data from a single study)
• Some imaging parameters (echographic particle image velocimetry, LV pressure-strain loops) are research tools without validated clinical cut-offs
• Conflict of interest: Badano and Muraru are consultants for GE Vingmed and TomTec Imaging; Migliore is consultant for Boston Scientific — potential bias toward imaging technologies

Key Concepts Mentioned

• concepts/LBBB-Criteria — ECG criteria (conventional, AHA 2009, Strauss strict); concordant/discordant; rate-dependent LBBB
• concepts/Cardiac-Resynchronization-Therapy — CRT indications, non-responder problem, imaging-based selection, systolic stretch index
• concepts/Sgarbossa-Criteria — performance data (meta-analysis), modifications (Smith, Selvester, QRS area)
• concepts/ECG-Conduction-Disturbances — LBBB criteria table; AHA 2009 context

Key Entities Mentioned

• entities/Vectorcardiography — VCG as true LBBB identifier; QRS area as CRT predictor (referenced in context)

Wiki Pages Updated

• wiki/sources/lbbb-europace-2017.md — Created (this file)
• wiki/concepts/LBBB-Criteria.md — Added TAVR-induced LBBB, pathophysiology, echocardiographic CRT predictors
• wiki/concepts/Cardiac-Resynchronization-Therapy.md — Added imaging-based CRT selection section and systolic stretch index
• wiki/concepts/Sgarbossa-Criteria.md — Added meta-analysis performance data and proposed modifications
• wiki/sourceindex.md — New entry prepended
• wiki/wikiindex.md — No new pages; existing entries confirmed
• log.md — Ingest entry appended