Circulation: Arrhythmia and Electrophysiology

REVIEW

Left Bundle Branch Block

Current and Future Perspectives
Nicholas Y. Tan , MD, MS; Chance M. Witt, MD; Jae K. Oh, MD; Yong-Mei Cha , MD

ABSTRACT: Left bundle branch block may be due to conduction system degeneration or a reflection of myocardial pathology.
Left bundle branch block may also develop following aortic valve disease or cardiac procedures. Patients with heart failure
with reduced ejection fraction and left bundle branch block may respond positively to cardiac resynchronization therapy. Lead
placement via the coronary sinus is the mainstay approach of cardiac resynchronization therapy. However, other options,
including physiological pacing, are being explored. In this review, we summarize the salient pathophysiologic and clinical
aspects of left bundle branch block, as well as current and future strategies for management.

Key Words: aortic valve ◼ atrioventricular node ◼ cardiac resynchronization therapy ◼ heart failure ◼ left bundle branch block

O
ver the years, important questions regarding the septum; most of these fibers course into the left bun-
clinical implications of left bundle branch block dle branch (LBB) before continuing as the right bundle
(LBBB) with/without known cardiovascular disease branch (RBBB).2 The LBB emerges from the inferior
continue to be raised. In this review, we summarize the border of the membranous septum at the base of the
literature behind the physiology and pathogenesis of
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interleaflet triangle between the right and noncoronary

LBBB, along with its definitions, clinical aspects, and aortic leaflets; this then divides into anterior and pos-
management strategies. terior fascicles, which course towards the anterior and
posterior papillary muscles of the left ventricle (LV)
respectively.2 A septal division, which can arise from the
ATRIOVENTRICULAR CONDUCTION anterior/posterior fascicle or the main LBB, has been
SYSTEM PHYSIOLOGY AND LBBB described as well.2 Distally, the bundle branches divide
PATHOPHYSIOLOGY and spread diffusely along the subendocardium of the
The atrioventricular node is found within the triangle of ventricles, forming Purkinje networks that facilitate ter-
Koch. The triangle’s apex, bound by the tendon of Tod- minal electrical conduction into the ventricular tissue.2
aro and the septal attachment of the tricuspid valve, is The His bundle is perfused by the atrioventricular nodal
occupied by the atrioventricular component of the mem- artery as well as the septal perforator of the left ante-
branous septum (Figure 1A). The His bundle is a cylin- rior descending artery. Unlike the RBBB, which receives
drical fascicle that connects the atrioventricular node to blood almost exclusively from the septal perforators, the
the bundle branches.1 Histologically, it consists of large LBB is supplied by both the left anterior descending and
Purkinje type cells that are separated by collagen and right coronary artery.3 Figure 1B highlights the anatomic
consequently are oriented in a longitudinal fashion.1 fate of the LBB and its intimate relationship with the
The His bundle passes through the annulus fibrosis and aortic valve as it emanates through the membranous
runs below the atrial aspect of the membranous sep- septum.4 Figure 2 provides a demonstration of the rela-
tum before going through the central fibrous body.2 It tionship between His and LB activation in an electro-
then carries fibers along the crest of the interventricular physiology study.

Correspondence to: Yong-Mei Cha, MD, Consultant, Department of Cardiovascular Medicine, Department of Medicine, Cardiac Device, Mayo Clinic, 200 1st St
Southwest Rochester, MN 55905. Email ycha@mayo.edu
For Sources of Funding and Disclosures, see page 374.
© 2020 American Heart Association, Inc.
Circulation: Arrhythmia and Electrophysiology is available at www.ahajournals.org/journal/circep

Circ Arrhythm Electrophysiol. 2020;13:e008239. DOI: 10.1161/CIRCEP.119.008239 April 2020 364

 Tan et al Left Bundle Branch Block Review

series), isolated left posterior fascicular block is much

Nonstandard Abbreviations and Acronyms rarer, occurring in around 0.1% of individuals.6,7 Fig-
ure 4A depicts the normal histology of the LBB along-
ACCF American College of Cardiology side a pathological example from a patient with familial
Foundation LBBB (Figure 4B).
AHA American Heart Association
BBRVT bundle branch reentry ventricular
tachycardia DEFINITIONS OF LBBB
CAD coronary artery disease The American Heart Association (AHA), American
CRT cardiac resynchronization therapy College of Cardiology Foundation (ACCF), and Heart
HBP His bundle pacing Rhythm Society (HRS) collaborated on an updated
HCN hyperpolarization-activated cyclic set of definitions for cardiac conduction disturbances
nucleotide-gated in 2009 (and restated in 2018).8,9 Strauss et al5 then
HRS Heart Rhythm Society proposed more stringent criteria for LBBB to better pre-
LBBB left bundle branch block dict cardiac resynchronization therapy (CRT) respond-
LV left ventricle/ventricular ers. This was motivated by the observation that patients
PPM permanent pacemaker with true LBBB—as opposed to those with conduction
RBB right bundle branch
delay—were more likely to have more pronounced QRS
durations with evidence of slurring and notching. Table
RV right ventricle/ventricular
compares and contrasts the electrocardiographic criteria
SkM1 skeletal muscle sodium channel 1
defining LBBB.
TAVR transcatheter aortic valve replacement

PATHOGENESIS AND FUNCTIONAL

Lesions in the His bundle or its derivatives create SIGNIFICANCE
downstream disruptions in electrical conduction (Fig-
ure 3). On ECG, LBBB is manifested by a widened QRS Electrical Dyssynchrony
complex with characteristic features described in the In an intact conduction system, signals rapidly pass
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next section and in Table. through the His bundle (≈1.5 m/s) to the bundle
As discussed in further detail later, an LBBB-like pat- branches and Purkinje network.10 The fast conduction
tern can be seen in the setting of myocardial pathology. velocity is facilitated by the longitudinal arrangement of
Additionally, damage to the distributaries of the LBB can the cells and high saturation of gap junction proteins—
occur, resulting in left anterior and posterior fascicular specifically connexins 40, 43, and 45—along the longi-
blocks (left anterior fascicular block and left posterior tudinal ends.11,12 An LBBB pattern on the surface ECG
fascicular block, respectively). Whereas left anterior fas- can result from damage to the LBB itself, conduction
cicular block is relatively common in the general popula- delay within the fascicles or Purkinje fibers (to LV myo-
tion (ranging between 0.9% and 6.2% based on several cardium), or a combination of all. With LV myocardial

Figure 1. Anatomy of the cardiac conduction system and its relationship to surrounding structures.

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 Tan et al Left Bundle Branch Block Review

Figure 2. Intracardiac electrogram with a concomitant right-sided His and left bundle signal.
HRA indicates high right atrium; LB, left bundle; Rvad, right ventricular apex (distal); R HIS, right-sided His.

disease, gap junction proteins (especially connexin 43) is, therefore, paramount for His bundle pacing (HBP),
are significantly rearranged and lateralized; in addition, LBB area pacing, or optimizing CRT response.16
structural remodeling may also alter cell coupling among
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It should be mentioned that RBBB can actually mask

cardiomyocytes and fibroblasts.13 As such, the above- the presence of LBB delay. The lack of terminal negative
stated mechanisms create differing pathophysiologic forces (ie, S waves) in leads I and aVL are suggestive of
effects on ventricular electrical activation. With true concomitant LBB delay.18
LBBB, right ventricular (RV) activation occurs first, fol-
lowed by breakthrough activation of the LV endocardium
usually at the level of the mid-septum; the LV transseptal Mechanical Dyssynchrony
conduction time is on average 30 to 40 ms.14 The rest of During LBBB, the ventricular septum is activated during
the LV is activated in a homogenous but delayed fashion, isovolumic contraction (before aortic valve opening), which
with the latest site of activation occurring in the lateral stretches the posterior and lateral walls. These walls are
basal area. In contrast, some patients with LBBB on sur- then activated later in systole, with consequent passive
face ECG were found to have LV transseptal conduction stretching of the septal wall. The dyssynchronous motion
times of <20 ms, suggesting that these individuals may of the ventricular walls extends isovolumic contraction/
not have true or complete LBBB.15 This was redemon- relaxation times and results in decreased contraction effi-
strated in an intracardiac study of septal conduction ciency.19 Echocardiography has been integral in visualizing
among 72 patients with LBBB pattern on surface ECG, the effects of LBBB on ventricular contraction. Charac-
whereby 26 (36%) were noted to have intact Purkinje teristic echocardiographic observations include (1) sep-
activation.16 Furthermore, the activation wavefront pat- tal beaking (or flush), where there is a leftward motion of
tern appears more heterogeneous with LBBB and con- the interventricular septum at or before ejection followed
comitant structural heart disease.15 Finally, the presence by a paradoxical rightward motion20 and (2) apical rock-
of left axis deviation leads to activation happening latest ing, where there is a short motion of the apex towards
in the anterior wall, which can have significant implica- the interventricular septum during ejection followed by a
tions for CRT.17 In this case, placing the LV lead in the longer motion towards the late-activated lateral wall.20,21
anterolateral position may allow for dyssynchrony correc- Two-dimensional strain analysis has also been used to
tion. Taken together, LBBB as manifested on electro- identify features associated with LV dyssynchrony. These
cardiography likely reflects a complex interplay between features include (1) early contraction of ≥1 basal/midseg-
intrinsic conduction system degeneration and LV myo- ment in the septal/anteroseptal wall and early stretching in
cardial disease; identifying the predominant mechanism ≥1 basal/midsegment in the opposing wall; (2) early peak

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 Tan et al Left Bundle Branch Block Review

Figure 3. Potential conduction blocks in the His bundle and left bundle branch (LBB).
1, Atrioventricular nodal block; 2: LBB block (LBBB); 3: left posterior fascicular block; and 4: left anterior fascicular block. Inline: ECGs of
typical LBBB (top) and LBBB-like pattern in hypertrophic cardiomyopathy (bottom). Although the QRS durations are >140 ms in both, there is
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clear mid-QRS notching in leads I and aVL for the former, whereas the QRS complexes are smooth and symmetrical in the latter.

contraction occurring within the first 70% of the systolic in association with LBBB.23 Nuclear imaging allows for the
ejection phase; and (3) early stretching wall showing peak assessment of mechanical dyssynchrony as well.21 Just as
contraction after aortic valve closure.22 In addition to high- in echocardiography, these advanced imaging techniques
lighting the mechanical consequences of conduction delay, may be helpful in distinguishing between responders and
such imaging characteristics have been helpful in predict- nonresponders of CRT therapy.23
ing patient responses to CRT.20,22
Other imaging modalities have also been successfully
utilized in the context of LBBB. Metrics for cardiac mag- Associated Genetic Factors
netic resonance imaging have been developed to quantita- Although LBBB is not generally considered a heri-
tively characterize the extent of mechanical dyssynchrony table disorder, studies have implicated several genetic

Table. Criteria Used to Define Complete LBBB in Adults

Electrocardiographic Criterion AHA/ACCF/HRS (2009, 2018) Strauss et al5

QRS duration ≥120 ms ≥140 ms (men), ≥130 ms (women)
Left-sided leads (I, aVL, V5, V6) Broad notched or slurred R waves Broad notched or slurred R waves*
Absent Q waves (with possible exception of aVL)
Occasional RS pattern in V5 and V6
Right-sided leads (V1, V2, V3) Small initial r waves in V1-3 Broad notched or slurred mid-QRS*
QS or rS in leads V1 and V2
R peak time >60 ms in V5 and V6 but can be normal in V1-3 Not specifically mentioned
ST and T waves Usually opposite in direction to QRS Not specifically mentioned
Positive concordance (upright T wave with upright
QRS) may be observed

ACCF indicates American College of Cardiology Foundation; AHA, American Heart Association; HRS, Heart Rhythm Society; and LBBB, left bundle branch
block.
*≥2 leads (I, aVL, V1, V2, V5, V6).

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 Tan et al Left Bundle Branch Block Review

Figure 4. Histology and pathology of the left bundle branch (LBB).

A, Normal appearance of the LBB (×12.5 magnification, hematoxylin and eosin stain), which appears lighter in color than the surrounding
myocardium. B, Atrophy of the LBB in a patient with familial LBB block (×25 magnification, Verhoeff-van Gieson stain).

mutations in association with bundle branch block. LBBB and cardiovascular disease,29 data from the Fram-
These mutations may involve: ion channel genes (includ- ingham study showed a significantly elevated risk of car-
ing HCN4 [hyperpolarization-activated cyclic nucleotide- diovascular deaths (50% within 10 years of onset) among
gated 4]), gap junction proteins, desmosomal genes, and individuals with LBBB.30 More recent studies have high-
cardiac transcription factors.24–26 Genetically mediated lighted LBBB as an independent predictor for adverse
bundle branch block tends to be progressive in nature, events, including sudden cardiac death (10 fold incidence
with many individuals developing complete atrioventric- increase)31as well as mortality from HF (3.08× increased
ular block or sudden cardiac death.26 risk) and myocardial infarction (2.90× increased risk),32
particularly among individuals aged 50 years and above.31
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Furthermore, in a Swedish prospective study of middle-

Electromechanical Effects of Right Ventricular aged men spanning 28 years, LBBB at baseline was
Pacing associated with a markedly increased risk of high-grade
RV pacing shares physiological similarities to LBBB, in atrioventricular block compared with men without bundle
that a pacing stimulus in the RV causes late activation branch block (adjusted risk ratio, 12.9).33 Hence, although
of the LV free wall and consequent electromechanical the prognosis of LBBB in younger patients may be rela-
dyssynchrony. At the cellular level, RV pacing has also tively benign, its presence in older subjects may serve as
been shown to induce profound changes in LV apoptotic an important marker for cardiovascular disease or death.
pathways and calcium-handling.27 Nevertheless, many
studies have identified subtle differences in activation Rate-Related LBBB and Painful LBBB
patterns between the two. Transseptal conduction time
Syndrome
appeared to be lower with RV pacing than in LBBB.28
Furthermore, although LBBB was associated with a cir- Tachycardia-related LBBB is believed to be caused by a
cumferential LV activation pattern, RV pacing may intro- defect in phase 3 (ie, repolarization) conduction at faster
duce heterogeneity in wavefront propagation due to its rates, whereby impulses are delayed or blocked entirely
propensity for resolving or exaggerating existing con- when they fall in the refractory period of the action
duction barriers.28 Despite these observed differences, potential. However, bradycardia-related LBBB may be
RV pacing is believed to induce comparable effects on related to spontaneous diastolic (phase 4) depolariza-
hemodynamics and resultant heart failure (HF).19 tion of the LBB at slower heart rates, thereby causing
it to be refractory to the subsequent conducted impulse.
Rate-dependent LBBB has been associated with acute
CLINICAL FEATURES AND PROGNOSIS decreases in cardiac systolic function34; in addition,
there have been case reports of acute systolic HF with
Natural History of LBBB rate-dependent LBBB.35 Shvilkin et al36 also presented
The prognosis of LBBB in asymptomatic individuals a series of patients with painful LBBB syndrome, char-
remains controversial. Although a study among US Air- acterized by chest pain during intermittent LBBB and
force personnel did not reveal an association between exclusion of myocardial ischemia as the trigger.

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 Tan et al Left Bundle Branch Block Review

LBBB in Association With Coronary Artery of transcatheter aortic valve replacement (TAVR)
Disease and Acute Myocardial infarction has markedly transformed the landscape of the man-
agement of aortic stenosis.44 However, conduction
Analyses of patients with LBBB and concomitant coro-
abnormalities—including LBBB and high-grade atrio-
nary artery disease (CAD) demonstrated increased risks
ventricular block requiring permanent pacemaker (PPM)
of adverse outcomes in comparison to patients with CAD
implantation—are commonly noted complications.4,45 The
but no LBBB (2.9-fold increased risk of cardiovascular
incidence of new-onset LBBB may be as high as 65%,
mortality and 1.4-fold increased risk of all-cause mortal-
ity).30,37 Similarly, among patients who underwent nuclear with the majority occurring intraprocedurally or within
exercise testing for known or suspected CAD, LBBB was 24 hours postprocedure.46 The self-expandable CoreV-
independently associated with a 50% increase in all-cause alve system (Medtronic, Minneapolis, MN) has a higher
mortality.38 Furthermore, underlying LBBB may confound observed incidence of LBBB and atrioventricular block
stress test findings, thereby affecting clinicians’ ability to compared with the Edwards SAPIEN devices (Edwards
identify obstructive CAD among these patients.39 Because Lifesciences LLC, Irvine, CA); specifically, the CoreValve
of the asynchronous activation of the interventricular sep- was associated with LBBB and PPM risks of 18% to
tum with LBBB, assessing for wall motion abnormalities 65% and 25% to 28%, respectively, compared with 4%
with echocardiography becomes more challenging, partic- to 30% and 5% to 7%, respectively, for the Edwards
ularly during tachycardia. However, its diagnostic accuracy SAPIEN valves.4,45 Procedural factors such as prosthe-
may be improved significantly with the use of myocar- sis implantation depth within the LV outflow tract47 and
dial contrast administration.40 Nuclear perfusion stud- extent of LV outflow tract stretching by balloon dilation
ies of patients with LBBB, however, have shown relative or device implantation48 are associated with increased
hypoperfusion in the interventricular septum along with risk of new-onset LBBB as well. Approximately 13% of
increased blood flow to the lateral wall; this relative septal patients with new LBBB post-TAVR have been noted to
hypoperfusion may become exaggerated during exercise, develop high-grade atrioventricular block before or after
thereby leading to false-positive interpretations of signifi- discharge.49 A recent meta-analysis also showed a 2-fold
cant CAD in the left anterior descending territory.41 When increased risk of PPM implantation among patients with
LBBB is present, 3 key findings have been suggested to new-onset post-TAVR LBBB.50 Such observances high-
correlate true ischemia (1) reversible perfusion defect(s), light the need for close electrocardiographic monitoring
especially at end-diastole; (2) concomitant apical defect,
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of post-TAVR patients. The incidence of LBBB following

and (3) systolic dysfunction matching the identified per-
surgical aortic valve replacement is ≈5%; unlike TAVR,
fusion defect(s).21 ECG-gating and vasodilator-based
the long-term implications of postsurgical aortic valve
myocardial perfusion imaging techniques are also helpful
replacement LBBB remain unclear.51
in improving its accuracy.41 There are no recent studies
comparing stress echocardiography and nuclear imaging
in the setting of LBBB; however, both are preferable to LBBB following Surgical Septal Myectomy
exercise ECG testing.39
Alcohol septal ablation and surgical septal myectomy
Given the high mortality ascribed to acute myocar-
have been shown to relieve LV outflow tract obstruction
dial infarction associated LBBB, new or presumed new
among patients with hypertrophic obstructive cardiomy-
LBBB was previously considered diagnostic of acute
myocardial infarction. However, confirming the onset of opathy, the latter of which is generally preferred in high-
LBBB can be challenging, particularly if no prior ECGs volume centers.52 Surgical septal myectomy frequently
exist.42 As such, the 2013 ACCF/AHA guidelines for leads to LBBB (up to 40%).53 However, the long-term
the management of ST-segment–elevation myocardial implications of this outcome are unknown. In contrast,
infarction recommended that isolated new LBBB should complete heart block following septal myectomy is rare
not be considered an ST-segment–elevation myocardial (<2%)54; risk factors include preexisting RBBB block
infarction equivalent.43 Although LBB injury is represen- and prior septal alcohol ablation (which frequently leads
tative of a sizeable anterior/anteroseptal infarct, perma- to RBBB block).52
nent pacing has not been shown to improve survival in
this circumstance.9
LBBB in Dilated Cardiomyopathy
Conduction abnormalities may develop in ischemic/non-
LBBB Following Aortic Valve Disease or ischemic cardiomyopathy due to degeneration/fibrosis
Replacement of the conduction system, adverse ventricular remodel-
Invasive aortic valve interventions have the potential ing, or ischemia. In patients with HF with reduced ejec-
of damaging the conduction system given the close tion fraction, the presence of LBBB is associated with
anatomic relationship highlighted earlier. The advent increased mortality.55,56

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 Tan et al Left Bundle Branch Block Review

Bundle Branch Reentry Ventricular Tachycardia CURRENT AND FUTURE MANAGEMENT

Bundle branch reentry ventricular tachycardia (BBRVT) OF LBBB
is an uncommon and fascinating arrhythmia whereby the
Newly Diagnosed LBBB
bundle branches serve as essential components of the
reentrant circuit sustaining the tachycardia.57 Because In the 2018 AHA/ACCF/HRS guidelines on the evalu-
the bundle branches are part of the reentrant circuit, ation/management of bradycardia and conduction delay,
bundle branch catheter ablation (usually the right) is the patients with newly identified LBBB should be screened
treatment of choice in experienced centers.58 Underly- with echocardiography (Class I recommendation, level of
ing impairment of the His-Purkinje system is a prereq- evidence B) given the strong association between LBBB
uisite for BBRVT to develop. As such, BBRVT often and preexisting structural heart disease.9 Subsequent
occurs in the context of structural heart disease, includ- testing for obstructive CAD and heart block can be per-
ing dilated cardiomyopathy and valvular lesions59; rarely, formed based on clinical judgment as well.
it may manifest in isolated conduction system disease
or in individuals with genetic inclinations.60 A significant Painful LBBB Syndrome
proportion of patients with BBRVT have LBBB on sur-
Clinical suspicion for painful LBBB syndrome may be
face ECG during sinus rhythm.59 However, one study
raised in individuals whose chest pain paroxysms cor-
found that most patients with LBBB have preserved
relate temporally with intermittent LBBB after ruling
but slowed antegrade conduction across the LBB and
out myocardial ischemia. Additionally, ECG features that
posterior fascicle and that many demonstrated fixed or
may be associated with painful LBBB syndrome are an
functional left anterior fascicular block.61 These findings
inferior axis and low S/T wave ratio in the precordial
highlight the potential roles that the left fascicles play in
leads (<1.8).36 Proposed treatment options include beta-
facilitating BBRVT. In addition, it explains why complete
blocker therapy,67 CRT,36 and HBP.68
atrioventricular block is a rare complication of RBBB
ablation even among patients with complete LBBB pat-
tern on surface ECG.57,61 New-Onset LBBB Following TAVR
Given the elevated risk of developing high-grade
Structural Remodeling Associated With LBBB atrioventricular block in the first 48 to 72 hours post-
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TAVR, it is reasonable to keep patients in the hospi-

In a pivotal canine model experiment, induction of tal on telemetry monitoring during this period.4 If the
LBBB led to decreased LV ejection fraction (LVEF), LBBB persists beyond 72 hours, then consideration
increased LV cavity volume, and wall mass, as well as for outpatient surveillance can be given. Prophylactic
decreased septal perfusion, suggesting that the elec- PPM implantation may also be reasonable in individu-
tromechanical dyssynchrony from LBBB may have an als with markedly prolonged QRS durations (>150 ms),
important role in cardiac remodeling.62 Subsequently, although evidence for supporting this approach is lim-
Vaillant et al63 described a series of patients with ited. The 2018 American College of Cardiology/AHA/
LBBB and initial normal LVEF who developed HF with HRS guidelines on the evaluation and management of
reduced ejection fraction over time and were treated patients with bradycardia and cardiac conduction delay
successfully with CRT. These data, as well as evi- offers a Class IIB indication for PPM implantation in
dence from CRT trials highlighting the efficacy of CRT post-TAVR patients with LBBB.9
among patients with LBBB, prompted consideration
of cardiomyopathy primarily caused by LBBB (dyssyn-
chronopathy).64 Early recognition of HF with reduced HF and LBBB
ejection fraction in association with LBBB-induced Patients with HF with reduced ejection fraction and
dyssynchrony is important, as there can be significant concomitant LBBB represent a major target group for
implications with regards to prognosis and therapy. In CRT, as a number of studies have found that these
the NEOLITH studies (New-Onset LBBB-Associated patients may be less likely to respond positively to
Idiopathic Nonischemic Cardiomyopathy), patients with guideline-based medical therapy for HF compared
LBBB were less likely to have improvements in LVEF with patients with normal QRS duration.66,69 Since the
following goal-directed medical therapy than their nar- early 2000s, a number of landmark randomized con-
row QRS complex counterparts; furthermore, patients trolled trials—including MUSTIC (Multisite Stimulation
with LBBB who received early CRT (≤9 months) were in Cardiomyopathies),70 COMPANION (Comparison of
more likely to achieve LVEF>35% versus those who Medical Therapy, Pacing, and Defibrillation in Heart
received CRT after 9 months.65,66 These findings high- Failure),71 and MADIT-CRT (Multicenter Automatic
light potential benefits in early CRT for patients with Defibrillator Implantation Trial With Cardiac Resyn-
dyssynchronopathy. chronization Therapy)72—reported significant benefits

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 Tan et al Left Bundle Branch Block Review

in HF symptoms/hospitalizations and mortality among QRS≥150 ms but not <140 ms).74,80 It should be noted
patients with LVEF<35% and QRS duration >120 that women with narrower QRS durations may respond
ms who received CRT. In a subgroup analysis of the positively to CRT as well.74 Furthermore, studies have
MADIT-CRT trial, patients with QRS duration <150 ms found that application of the Strauss criteria was help-
did not appear to derive benefit from CRT72; this rela- ful in predicting remodeling following CRT, suggesting
tionship is well visualized in data from the REVERSE its potential utility in selecting appropriate patients for
trial (Figure 5).73 Furthermore, the type of intraventricu- therapy.81
lar conduction delay may affect CRT response, where The effect of CRT on cardiovascular and mortality
LBBB but not RBBB block or nonspecific conduction outcomes on patients with less severe LV dysfunction
delay was associated with improvement in outcomes (ie, LVEF>30%–35%) remains uncertain. Substudies
following CRT.74 The Echo-CRT trial (Echocardiogra- of randomized controlled trials suggested that patients
phy Guided Cardiac Resynchronization Therapy), which with LVEF>30% to 35% may benefit from CRT.82
enrolled patients with QRS duration <130 ms and echo- Interestingly, a retrospective analysis of patients with
cardiographic evidence of mechanical dyssynchrony, LVEF of 36% to 50% found that concomitant LBBB
also showed that CRT was associated with increased was associated with poorer cardiovascular outcomes
mortality.75 As such, major US (American College of (LVEF decrease, need for implantable cardioverter-
Cardiology/AHA/HRS)76 and European Society of defibrillator implantation, and mortality).56 Thus, there is
Cardiology guidelines77,78 were consistent in issuing burgeoning literature highlighting the potential benefit
Class I and IIA recommendations for CRT in individu- of CRT among individuals with moderate degrees of LV
als with QRS>150 ms alongside LBBB and non-LBBB dysfunction and LBBB.
morphologies, respectively. In contrast, the European Special mention should be made of patients with
Society of Cardiology HF Association revised the QRS depressed LVEF who require frequent ventricular
duration cutoff for CRT to 130 ms (regardless of QRS pacing. In the BLOCK HF randomized controlled
morphology) largely due to results from Echo-CRT,79 trial (Biventricular Versus Right Ventricular Pacing in
whereas the 120 ms cutoff for CRT consideration Heart Failure Patients With Atrioventricular Block),
remained unchanged in the AHA/ACCF/HRS guide- patients in the RV paced group had higher rates of
lines. Additionally, in New York Heart Association class adverse outcomes (all-cause mortality, urgent visit
II to IV patients with HF with LBBB and QRS durations for HF, and ≥15% increase in LV end-systolic volume
between 130 and 149 ms, the European Society of index) compared with patients in the biventricular
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Cardiology HF Association offered a class I recom- paced group. 83 These results, along with data from the
mendation for CRT, differing from the class IIa recom- MOST (Mode Selection Trial in Sinus Node Dysfunc-
mendation by the AHA/ACCF/HRS; the rationale for tion) 84 and DAVID (Dual Chamber and VVI Implant-
the latter recommendation was made based on the able Defibrillator) 85 trials, contributed to the Class IIa
subgroup analyses in MADIT-CRT and RAFT (Resyn- recommendation for biventricular pacing (and Class
chronization-Defibrillation for Ambulatory Heart Fail- IIb for HBP) in patients with LVEF between 36%
ure Trial) (whereby benefits were seen in patients with and 50% who require >40% ventricular pacing per

Figure 5. The relationship between QRS duration and response to cardiac resynchronization therapy (CRT) based on data from
the REVERSE trial (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction).
Reprinted from Poole et al73 with permission. Copyright © 2016, Elsevier.

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 Tan et al Left Bundle Branch Block Review
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Figure 6. Longitudinal dissociation of conduction fibers within the His bundle.

Proximally, conduction fibers are predestined to form left (green and magenta) and right (blue) bundle branches. Lesions within the His bundle
can, therefore, lead to left bundle branch block (left). Pacing distal to the lesion allows for restoration of normal conduction (right). AVN
indicates atrioventricular node.

the 2018 AHA/ACCF/HRS bradycardia and con- American College of Cardiology/AHA Guideline for
duction delay guidelines.9 Finally, for patients with the Management of HF offers a class IIa recommen-
LVEF<35% and >40% ventricular pacing, the 2013 dation for CRT.76

Figure 7. Anatomic illustrations of physiologic pacing techniques.

A, Selective His bundle pacing; (B) nonselective His bundle pacing; (C) left bundle branch area pacing.

Circ Arrhythm Electrophysiol. 2020;13:e008239. DOI: 10.1161/CIRCEP.119.008239 April 2020 372

 Tan et al Left Bundle Branch Block Review

His Bundle and LBB Area Pacing of longitudinal dissociation has not gone unchallenged;
for example, Lazzara et al87 demonstrated evidence for
Seminal light and electron microscopy studies by James
the presence of interconnecting transverse conducting
and Sherf1 provided histological evidence that conduc- fibers within the His bundle, allowing for a small residual
tion fibers within the His bundle are predestined to form intact bundle following an incision to activate the whole
the LBB and RBBB. As such, bundle branch block can bundle distal to the incision without affecting the activa-
result from a relatively proximal lesion within the His tion pattern significantly. This led to the postulation of
bundle. Subsequently, Narula et al86 was able to correct other possible mechanisms for how HBP can correct
LBBB in a series of patients by pacing the His bundle, bundle branch block, including (1) source-sink mismatch,
thereby providing powerful evidence for the longitudinal where there is insufficient voltage gradient for depolar-
dissociation of conduction fibers within the His bundle ization between proximal conducting cells (source) and
(Figure 6). Despite these supportive findings, the concept distal His-Purkinje system (sink) and an increase in
Downloaded from http://ahajournals.org by on March 5, 2024

Figure 8. Electrocardiograms demonstrating physiologic pacing.

A, Selective His bundle pacing, QRS duration 108ms; (B) nonselective His bundle pacing, QRS duration 118ms; (C) left bundle branch area
pacing, QRS duration 104ms.

Circ Arrhythm Electrophysiol. 2020;13:e008239. DOI: 10.1161/CIRCEP.119.008239 April 2020 373

 Tan et al Left Bundle Branch Block Review

source power can facilitate depolarization of distal tis- CONCLUSIONS

sue; and10 (2) virtual electrode polarization, where an
LBBB has profound hemodynamic and clinical implica-
electrical stimulus generates regions of depolarization/
tions even among asymptomatic individuals, and its pres-
hyperpolarization around the electrode tip which in turn
ence is associated with a multitude of cardiac diseases.
creates potential pathways for propagation through exci-
Prompt identification of LBBB, particularly in certain clin-
tation of previously refractory tissue.88 Broadly speaking,
ical scenarios, is, therefore, critical in determining optimal
HBP can be selective (His bundle is the only tissue cap-
management strategies for patients.‍
tured by pacing; Figure 7A) or nonselective (fusion cap-
ture of His bundle and adjacent ventricular myocardium;
Figure 7B)89; data thus far do not suggest a significant ARTICLE INFORMATION
clinical difference between either.90
Affiliation
HBP dissemination into clinical practice has been slow91 Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.
due to the initial lack of specialized equipment, steep opera-
tor learning curve, and concerns regarding pacing failure.92 Acknowledgments
We would like to thank Dr Melanie Bois and Dr William Edwards from the Mayo
The introduction of sheaths and delivery tool specifically
Clinic Department of Laboratory Medicine and Pathology for their help with pre-
designed for HBP has alleviated the technical challenges paring the histology images used in this article. We are also grateful to Michael
somewhat,10 and average successful implant rates have King and Alice McKinney for their tireless work with the medical illustrations.
been estimated at 84.6% since 2018.92 Importantly, most Sources of Funding
patients recruited had LBBB at baseline, suggesting that None.
HBP may indeed be helpful in correcting electrical dys-
synchrony even in the presence of infranodal disease. In a Disclosures
None.
small randomized study comparing HBP and conventional
biventricular CRT, HBP provided more effective ventricular
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