JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 7, NO.

7, 2021

ª 2021 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

PUBLISHED BY ELSEVIER

The Role of the Left Septal Fascicle in

Fascicular Arrhythmias
Clinical Presentation and Laboratory Evaluation

José M. Sanchez, MD,a,* Satoshi Higuchi, MD,b,* Tomos E. Walters, MBBS, PHD,b Vasanth Vedantham, MD, PHD,b
Henry Hsia, MD,b Edward P. Gerstenfeld, MD,b Nitish Badhwar, MBBS,c Mariana Albona, MD,d Mario Njeim, MD,d
Melvin M. Scheinman, MDb

ABSTRACT

OBJECTIVES This study describes a series of cases best explained by invoking the left septal fascicle (LSF) as a critical
component of the arrhythmia circuit.

BACKGROUND Numerous anatomic studies have shown evidence of the LSF, but its precise role in the onset of
arrhythmia is unclear.

METHODS This paper presents 5 cases that implicated the LSF as a critical component of arrhythmogenesis.

RESULTS The first case had ventricular fibrillation repeatedly documented after a single premature atrial complex,
produced left-sided conduction delay and simultaneous earliest activation of the left anterior fascicle (LAF) and left
posterior fascicle (LPF). The LSF was ablated, resulting in an arrhythmia cure. The second case showed narrow QRS
morphology during fascicular re-entrant tachycardia. The earliest mid-septal diastolic potentials had distal-to-
proximal activation suggesting an LSF as a retrograde common pathway. The third case, with multiple ectopic
Purkinje-related premature complexes exhibited earliest Purkinje potentials in the mid-septum, with subsequent
anterograde activation of the LAF and LPF. Ablation of the LSF eliminated the premature ventricular complexes
(PVCs). The fourth case demonstrated LPF and LAF PVCs. The His-left bundle activation showed earliest potentials at
the proximal insertion of the left bundle during LPF PVCs, as well as a distal-to-proximal activation pattern
during LAF PVC, suggestive of LSF involvement. The fifth case had focal non–re-entrant fascicular beats successfully
ablated over the LSF.

CONCLUSIONS Involvement of the LSF is suspected with presentation of multiform fascicular and narrow
QRS complex ventricular episodes of arrhythmia. Diagnoses and ablation require detailed mapping of the entire
left sided conduction system. (J Am Coll Cardiol EP 2021;7:858–70) © 2021 by the American College of
Cardiology Foundation.

I diopathic fascicular episodes of arrhythmia typi-

cally involve re-entry within the conduction
system in structurally normal hearts. Histologic
analysis of the left ventricular (LV) conduction
system in humans has shown that it is composed of
3 fascicles: anterior, posterior, and septal (1,2). The
left septal fascicle (LSF) can originate directly from
the left bundle (LB) or from tributaries from the left
anterior fascicle (LAF) and left posterior fascicle
(LPF) before arborizing into a network that inserts

From the aSection of Cardiac Electrophysiology, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora,
Colorado, USA; bSection of Cardiac Electrophysiology, Division of Cardiology, University of California-San Francisco, San Fran-
cisco, California, USA; cSection of Cardiac Electrophysiology, Division of Cardiology, Stanford University Medical Center, San
Francisco, California, USA; and the dSection of Cardiac Electrophysiology, Division of Cardiology, Saint Joseph University, Hotel-
Dieu de France Hospital, Beirut, Lebanon. *Drs. Sanchez and Higuchi contributed equally to this work.
William Stevenson, MD, served as Guest Editor-in-Chief for this paper.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’
institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information,
visit the Author Center.

Manuscript received September 24, 2020; revised manuscript received November 24, 2020, accepted December 16, 2020.

ISSN 2405-500X/$36.00 https://doi.org/10.1016/j.jacep.2020.12.012

JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 7, NO. 7, 2021
JULY 2021:858–70
into the left mid septum (2). Careful mapping studies
in humans have defined the trifascicular specialized
conduction system (3,4). The LSF is characterized by
a significant reduction in conduction velocity attrib-
uted to regional distribution of gap junctions and a
load mismatch caused by intense branching of Pur-
kinje fibers (5), and conceivably, conduction slowing
or blockage may result in a propensity for re-entrant
fascicular tachycardias involving the LSF (6,7).
Fascicular tachycardia events that rely on the LSF
are challenging to identify and, apart from upper
septal fascicular tachycardias, there are rare reports
implicating the role of the septal fascicle (7–11). This
series presents 5 cases of fascicular episodes of
arrhythmia that are best explained by involvement
of the LSF as a critical component of the arrhythmia
circuit. This report emphasizes the importance of sus-
pecting the LSF involvement when patients present
with multiform fascicular beats. In addition, the
importance of careful mapping of the trifascicular
system is emphasized.
METHODS
Five cases were collected from April 1, 2018, to
September 1, 2019. These cases were treated at 3
centers: University of California at San Francisco,
Stanford University Medical Center, and Saint Joseph
University in Beirut, Lebanon. The ablative procedure
was left to the discretion of the treating physician.
Medical records were retrospectively reviewed to
obtain demographic and clinical data. All patients
were de-identified. Ethical approval was not
required.
RESULTS
RE-ENTRANT VENTRICULAR ARRHYTHMIAS INVOLVING
THE LSF. C a s e 1 . A 29-year-old man with no signifi-
cant medical history presented after an aborted car-
diac arrest. He was also noted to have an episode of
ventricular tachycardia (VT) with right bundle and
superior axis (Figure 1A). Previous evaluation showed
a normal cardiac CMR. He was referred for an EP
study at which point spontaneous episodes of ven-
tricular fibrillation (VF) were observed (Figure 1B). All
episodes were initiated by a premature atrial complex
(PAC), which resulted in a left bundle branch aberra-
tion, followed by multiform fascicular beats and then
VT/VF. This sequence was reproducible with a single
atrial extrastimulus. The QRS pattern, short His-
ventricular (HV) interval of 9 ms, and an eccentric
pattern of His activation of the subsequent ventricu-
lar beats were suggestive of left-sided fascicular
Sanchez et al. 859
Arrhythmias of the Left Septal Fascicle
involvement. A duodecapolar catheter was ABBREVIATIONS
positioned on the LPF and then on the LAF, AND ACRONYMS
where a stereotypical pattern of pleiomorphic
Abl = ablation catheter ms
ventricular beats were observed with atrial
CS = coronary sinus
extrastimuli (Figure 2). The initial activation
HV = His-ventricular
of the LPF following the premature atrial
stimulus (A 2) was proximal-to-distal, with LAF = left anterior fascicle
LAF potentials recorded slightly later. The LB = left bundle
second ventricular beat after A 2 exhibited LPF = left posterior fascicle
eccentric activation in both the LPF and the LSF = left septal fascicle
LAF. The earliest potential in the LAF was LV = left ventricular
identical in timing to that in the LPF PAC = premature atrial
(Figure 2A, dotted line). It was hypothesized complex
that A2 resulted in a block of the septal PVC = premature ventricular
fascicle as well as an anterograde conduction complex
delay of the LAF and LPF, thereby allowing VF = ventricular fibrillation
subsequent retrograde septal activation. The VH = ventricular-Hisian
previously observed clinical VT (Figure 1A) VN = ventricular-nodal
was then able to be induced. Serial entrain- VT = ventricular tachycardia
ment resulted in progressive fusion thus
confirming a re-entrant mechanism consistent with
LPF VT (Supplemental Figure 1).
Linear ablation across the LPF then proceeded, and
a subcutaneous implantable cardiac-defibrillator was
inserted. The patient was discharged and subse-
quently presented with an implantable cardiac-
defibrillator shock. Device interrogation showed an
episode of PAC-induced VF (Supplemental Figure 2).
He returned to the electrophysiology laboratory at
which point VT/VF remained inducible following a
single atrial extrastimulus. An ablation procedure was
carried out, extending from the LPF into the mid-
septum, targeting the region of the LSF (Figure 3A).
Following this procedure, there were no episodes of
spontaneous or atrial extrastimuli-induced VT/VF. A
repeated EP study was performed 2 days later without
any further inducible VT/VF. Genetic testing yielded
a MYBPC3 variant of uncertain significance, and
routine device interrogations have noted no episodes
of arrhythmia despite frequent PACs over a follow-up
of more than 24 months.
C a s e 2 . A 44-year-old man with recurrent tachy-
cardia was referred for ablation. The tachycardia was
induced at a cycle length of 450 ms. There was evi-
dence of ventriculoatrial blockage and an abrupt
change in the QRS width at the same rate (Figure 4A).
Access to the LV was obtained, and the courses of
LSF, LAF, and LPF were defined. Mapping of the LV
septum recorded His-left bundle (LB) potentials as
well as distinct mid-diastolic potentials during sinus
rhythm (Figure 4B). The wide QRS tachycardia was
induced, and the earliest diastolic potentials were
observed along the mid-septum with a distal-to-
proximal activation pattern (Figure 4B). A single PVC
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Arrhythmias of the Left Septal Fascicle JULY 2021:858–70

F I G U R E 1 Case 1: Surface Electrocardiographic Recordings of the Clinical Arrhythmia

(A) Right-bundle, superior axis wide complex tachycardia suggestive of left posterior fascicular ventricular tachycardia. (B) Spontaneous
initiation of VF preceded by a PAC (arrow). The PAC is immediately followed by aberrant ventricular conduction and several beats of
pleiomorphic VT. PAC ¼ premature atrial complex; VF ¼ ventricular fibrillation.

reliably terminated the tachycardia (Supplemental
Figure 3), and critically timed PACs were observed
to advance the His deflection but not reset the
tachycardia (Figure 5A). Similar to the proposed
mechanism of upper septal VT, these findings were
most suggestive of a re-entrant circuit involving
retrograde LSF conduction during both narrow QRS
and wide QRS tachycardia. During attempts to entrain
from upper mid septal regions, catheter manipulation
apical to the LB terminated the tachycardia. Radio-
frequency lesions were placed at this location tar-
geting the earliest LSF (Figure 5B), which rendered
the tachycardia noninducible.
FOCAL PVCs ORIGINATING FROM THE LSF. C a s e 3 . A
20-year-old man with syncope, sinus bradycardia
with sinus pauses, and frequent multiform PVCs was
referred for PVC ablation. CMR imaging results were
notable for moderate LV systolic dysfunction and no
delayed gadolinium enhancement. Genetic evalua-
tion yielded a pathogenic heterozygous
mutation at c.656G>A (p.Arg219His), as well as MYPN
and SCN9A variants of uncertain significance. A pro-
cainamide infusion challenge was negative for type I
Brugada syndrome, and subsequent multiple ectopic
Purkinje-related premature contractions (MEPPC)
were diagnosed (12). Because of high PVC burden and
LV dysfunction, the patient was referred for ablation.
Three PVCs were observed during the EP study and
are shown in order of decreasing frequency
(Figure 6A). The HV interval was negative during PVC
1, suggestive of a more distal origin within the Pur-
kinje system (Figure 6B). A duodecapolar catheter was
positioned along the ventricular septum. The left-
sided His, LAF, LPF, and LSF were mapped. During
PVC 1, early Purkinje potentials were recorded along
the mid-septum following activation of the mid-LSF
region with variable anterograde activations of LAF
and LPF (Figure 6B). The earliest Purkinje potential
was recorded at the mid-septum preceding the QRS
onset by 33 ms (Figure 6C). Furthermore, anterograde
SCN5A activation of the LPF was still observed during variant
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F I G U R E 2 Case 1: Intracardiac Recordings of the Clinical Arrhythmia

Intracardiac electrograms at time of the initiation of stereotypic pleiomorphic ventricular beats with programmed atrial extrastimulus. (A) Single atrial extrastimulus
results in an LBB block pattern followed by eccentric activation of the LPF. The local potential at LAF d exhibits the earliest potential in the LAF. Note that the earliest
potentials in both the LAF and LPF were nearly simultaneous (dotted line). (B) Single atrial extrastimulus results in an eccentric activation pattern of the LAF. LAF ¼ left
anterior fascicle; LBB ¼ left bundle branch; LPF ¼ left posterior fascicle.

forms of PVC 1 (Figure 7A). An early fractionated C a s e 4 . A 42-year-old woman was referred for eval-
Purkinje signal was found at the distal mid-septum uation of VT. She was noted to have a high burden of
during PVC 2, suggestive of LSF involvement PVCs believed to originate from both the LAFs and
(Figure 7B). It was hypothesized that the origin of the LPFs. Cardiac evaluation, including exercise stress
PVCs was from the LSF followed by delayed activa- testing and CMR, showed reduced LV systolic func-
tion of the LAF and LPF. Linear ablation across the tion but no myocardial ischemia or delayed gadolin-
LPF and LSF was performed, resulting in the elimi- ium enhancement. Her condition was diagnosed as
nation of all PVCs. The patient was discharged PVC-mediated cardiomyopathy and was treated
home, and ambulatory surveillance monitoring medically, but she continued to experience frequent
showed a significant reduction of PVC burden from episodes of nonsustained VT as well as VT episodes
35% to 5% post-ablation. The patient was subse- lasting up to 4 min.
quently treated with quinidine, which reduced the During an EP study, frequent PVCs were observed
PVC burden to 0%. from the LPF (right bundle, leftward superior axis)
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Arrhythmias of the Left Septal Fascicle JULY 2021:858–70

F I G U R E 3 Case 1: Electroanatomical Map and Proposed Arrhythmia Schema

(A) 3-dimensional electroanatomical map depicting the LAF, LPF, and LSF in RAO (left) and left anterior oblique projections (right). Red circles denote ablation lesions
extending from the LPF into the septum empirically targeting the LSF. (B) Proposed schema of a PAC resulting in block in the LSF and relative delay in the LAF and LPF
resulting in LBB block pattern. This is followed by retrograde activation of the LSF and eccentric activation of the LAF and LPF leading to initiation of several beats of
organized fascicular re-entry followed by multiple micro-re-entrant circuits that degenerate into VF. RAO ¼ right anterior oblique; other abbreviations as in Figures 1 and 2.

and LAF (right bundle, rightward inferior axis)
(Figure 8A). The coupling intervals of the PVCs varied
even among PVCs with the same morphology. Retro-
grade aortic access was obtained and used to intro-
duce a multipolar mapping catheter positioned over
the anatomic course of the left-sided His and LB.
During sinus rhythm, proximal-to-distal activation of
the His bundle and LB was observed. During LPF
PVCs, the earliest activation at the proximal LB with
retrograde His activation, whereas during the LAF
PVCs, a distal-to-proximal activation pattern was
observed (Figure 8A). The multipolar catheter was
used to delineate the course of the LAF and LPF. An
ablation catheter was then inserted into the LV.
During ventricular episodes of arrhythmia of either
LPF or LAF morphology, recordings from the mid-
septum just apical to the LB showed a distal-to-
proximal activation pattern (Figure 8B). The earliest
fascicular activation was recorded over the upper
mid-septal region (Figure 8C), and ablation localized
to this region resulted in elimination of all episodes of
arrhythmia over a follow-up of 18 months.
C a s e 5 . A 19-year-old woman with recurrent palpi-
tations and presyncope had a high PVC burden with a
normal echocardiogram and CMR results. She was
referred for ablation for a dominant PVC of the right
bundle, leftward, and superior axis (Figure 9A). The
PVCs occurred sporadically and were not linked to the
preceding QRS complex. An activation map of the LV
was created using a duodecapolar catheter during
frequent PVCs. Fascicular potentials were recorded
along the mid-septum during sinus rhythm,
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F I G U R E 4 Case 2: Surface and Intracardiac Recordings of the Clinical Arrhythmia

(A) Induction of a tachycardia with an abrupt change in the QRS morphology from narrow to wide. Note that there is a slight decrease in the tachycardia cycle length that
may induce conduction block in the left anterior fascicle. The closed arrows depict dissociated P waves during both the narrow QRS and wide QRS tachycardia. (B)
Ablation catheter positioned along the left ventricular septum where areas of mid-diastolic potentials were recorded during sinus rhythm and a wide QRS tachycardia in
an area localized in the high mid-septal region just apical to the left bundle. Note that the diastolic potentials exhibit a retrograde activation pattern during wide QRS
tachycardia.

consistent with anterograde activation of the septal
fascicle (Figure 9B). During the clinical PVCs, these
mid-septal potentials showed the earliest activation
in the middle of the LSF. The earliest local potential
at the mid-septum preceded the QRS onset by 40 ms
(Figure 9C). The authors postulated that this repre-
sented focal firing of the LSF and the retrograde
conduction to the LPF was faster than anterograde
LSF conduction, showing LPF PVC morphology.
Radiofrequency energy was applied to the LSF,
resulting in immediate suppression of the PVC.
DISCUSSION
Idiopathic fascicular tachycardia is usually due to re-
entry within the left-sided conduction system.
Detailed anatomic studies have delineated the pres-
ence of 3 fascicles in the human heart: the left ante-
rior, posterior, and septal fascicles. Different QRS
morphologies of fascicular VTs have been attributed
to involvement of specific fascicles, but the role of the
LSF has not been well described. The present study
serves to emphasize 3 major points: one should sus-
pect involvement of the LSF if the patient presents
with multiple fascicular forms, especially including
narrow complexes at the same rate. We also recognize
the difficulty of selective entrainment pacing of the
LSF due to the capture of the local myocardium,
catheter stability, and hemodynamic stability but
emphasize that there is strong evidence for LSF
involvement on the bases of evaluating the activation
sequences of the respective fascicles both in sinus
rhythm as well as during fascicular tachycardia.
RE-ENTRANT VENTRICULAR ARRHYTHMIAS INVOLVING
THE LSF. The induction of fascicular tachycardia from
the atrium is well known, but the finding of PAC-
induced VF in Case 1 is unique. That patient pre-
sented after an episode of LPF VT and documented
VF. Genetic testing revealed a variant of uncertain
significant of the MYBPC3 gene, which is associated
with autosomal dominant hypertrophic cardiomyop-
athy; however, association with episodes of
arrhythmia in the structurally normal heart is un-
known (13,14). It was hypothesized that the PAC
blocks in the LSF and conducts anterograde with
delay into the LAF and LPF producing left bundle
branch conduction delay. This is followed by retro-
grade activation of the LSF and eccentric, almost
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F I G U R E 5 Case 2: Summary and Proposed Arrhythmia Schema

(A) A critically timed PAC during the tachycardia captures the His without resetting the tachycardia. (B) The 3-dimensional electroanatomic map of the LV in the RAO
projection with ablation lesions along the mid-septum (dark red circles) targeting the LSF. (C) The proposed schema showing the circuits of the narrow QRS tachycardia
and wide QRS tachycardia. For a detailed description, see the text. Abbreviations as in Figures 1 to 3.

simultaneous, activation of both the LAF and the LPF,
with several beats of fascicular re-entry resulting in
VF (Figure 3B). Tachycardia cure resulted only after
carrying the ablative lesions into the mid-septal area.
This is, to the best of the present authors’ knowledge,
the first description of fascicular
arrhythmia triggered by a PAC. This differs from the
original description of PVC triggers as well as the
most recent description of PVC triggering pleomor-
phic fascicular episodes of arrhythmia from the distal
Purkinje system (15–17).
In Case 2, the tachycardia exhibited a narrow QRS
morphology, and the diastolic potentials during a
wide QRS tachycardia exhibited a distal-to-proximal
activation in the mid-septal area. The authors
hypothesized that the LSF inserted into the very
proximal portion of the LB allowing for episodic near-
simultaneous activation of the His-right bundle as
well as the LAF and LPF, yielding a narrow complex
tachycardia similar to that previously described as an
upper septal pattern (Figure 5C) (10). Cases of narrow
QRS tachycardias also have been explained by the
episodes of presence of ventricular-Hisian (VH) or ventricular-
nodal (VN) connection (18). Although such a connec-
tion is possible here, the measurement of the HV
interval during the tachycardia was shorter than that
during sinus rhythm, excluding a VN connection, and
the location of successful ablation was not the basal
para-Hisian region but rather along the upper mid LV
septum. In addition, multiple VH and VN pathways
would have to be invoked in order to explain the
observed narrow and wide tachycardia. The circuit in
this case was explained as involving re-entrant
tachycardia with retrograde activation of the LSF,
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F I G U R E 6 Case 3: Surface and Intracardiac Recordings of the Clinical Arrhythmia

(A) A 12 lead-ECG shows 3 types of PVCs. (B) Intracardiac electrograms along the LSF and LPF during PVC 1. Note that there was an eccentric activation along the LSF,
whereas there was an anterograde activation along the LPF. The closed arrows show the His electrograms. (C) Intracardiac electrograms show the earliest local potential
recorded at the LSF during PVC 1. ECG ¼ electrocardiography; other abbreviations as in Figures 1 to 3.

giving rise to either upper septal fascicular beats with
narrow QRS complexes (10) or a block in the LAF
resulting in wide QRS complexes with right bundle
branch block and LAF block morphologies (Figure 5C).
A recent contribution by Zhou et al. (19) described
12 patients who initially underwent ablation of an LPF
re-entrant tachycardia and subsequently developed a
fascicular tachycardia with a right axis deviation. The
latter arrhythmia revealed the earliest ventricular
activation over the left anterior or left anterograde
medial LV. The authors found that the earliest po-
tential of the LAF VT was still the earliest potential
over the LPF and a more proximal ablation was suc-
cessful (19). They proposed a circuit with a different
exit site from the LPF. Because they did not specif-
ically search for an LSF, there was no way of knowing
whether, in fact, the retrograde activation of the LSF
preceded the activation of both the LAF and LPF (19).
Another paper from a consortium of hospitals in Israel
described 4 of 57 patients who underwent ablations of
an LPF VT that recurred with an LAF VT morphology
(20). Although the treating physicians did not use
multipolar electrode catheters for mapping, it is of
interest that 3 of the 4 patients underwent successful
ablation over the proximal septal region, although 1
patient underwent a serial ablation of the LPF and
LAF.
FOCAL PVCs ORIGINATING FROM THE LEFT SEPTAL
FASCICLE. Case 3 presented with a classic clinical
picture of MEPPC. MEPPC is a SCN5A-related cardiac
channelopathy characterized by a gain-of-function
mutation of the voltage-gated sodium channel
Na v1.5 protein (12) in SCN5A responsible for a
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F I G U R E 7 Case 3: Summary and Proposed Arrhythmia Schema

(A) Intracardiac electrograms along the LPF during variant forms of PVCs 1. Note that presystolic potentials with an anterograde activation pattern can be observed. (B)
During PVC 2, an earlier local potential preceding the QRS onset by 48 ms can be found in the LSF. (C) The proposed explanation of the 3 PVC morphologies. During PVC
1, focal firing from the LSF activated to the LBB in a retrograde fashion followed by subsequent anterograde activation in the LAF and LPF. During PVC 2, conduction
block at the LAF region leads to a left superior axis. In contrast, during PVC 3, conduction block at the LPF region leads to a right inferior axis. Abbreviations as in
Figures 1 to 3.

spectrum of arrhythmia episodes that include car-
diac conduction disease and sinus node dysfunction.
MEPPC is associated with frequent PVCs of the right-
and left-bundle morphology that originated from the
fascicular system, and treatment
quinidine has been shown to be effective (12).
Although the fascicular involvement in MEPPC has
been well described, the present authors are not
aware of any prior studies assessing the pathophys-
iology or response to catheter ablation. In Case 3, it
was found that the earliest presystolic potentials
were along the mid-septal region, followed by the
anterograde activation of the LAF and LPF. It was
hypothesized that the PVCs originated from a focal
firing from the LSF and activated in a retrograde
fashion to left bundle branch, followed by subse-
quent anterograde activation of the LAF and LPF,
with different degrees of conduction block, which
with hydro- resulted in frequent fascicular PVCs of various mor-
phologies (Figure 7C). Subsequent ablation of the
LPF and the LSF resulted in a reduction in PVC
burden to 5%. The residual PVCs were treated with
hydroquinidine therapy. The authors postulated that
incomplete PVC eradication by ablation was due to
the multiplicity of connections from the LSF to the
LAF and LPF.
For case 4, the activation pattern of the His-LB
potentials during LPF PVCs was unique and best
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F I G U R E 8 Case 4: Surface and Intracardiac Recordings of the Clinical Arrhythmia

(A) During sinus rhythm, there is proximal-to-distal activation of the multipolar mapping catheter positioned along the left-sided His and LB; note the presence of a small
atrial electrogram is compatible with recording from the LV summit. During the LPF PVC, the activation of the His and LB has an eccentric pattern with early activation of
the His bundle. During the LAF PVC, the activation sequence reverses with distal-to-proximal activation. (B) During LPF and LAF PVCs, the ablation catheter exhibited a
distal-to-proximal activation when positioned along the proximal mid-septum. Absence of an atrial electrogram on the ablation catheter signal confirms that the catheter
position is just apical to the LB along the mid-septum. (C) 3D electroanatomical map depicts the LAF, LPF, and LSF in RAO projection. Orange circles denote fascicular
potentials. Red circles denote ablation lesions clustered along the proximal mid-septum. (D) The proposed explanation for the 2 PVC morphologies by depicting the
activation pattern of the left-sided His and LB (see details in the text). Abbreviations as in Figures 1 to 3.

explained by an LSF insertion into the LB (Figure 8D).
A distal-to-proximal activation pattern at the mid-
septum supported retrograde LSF conduction. The
limited ablation area in the upper mid-septum cured
both the LAF and LPF PVCs. This finding suggested
that the LAF PVCs were also associated with the LSF
origin and direct LSF insertion into the LAF leading to
a distal-to-proximal activation in the His-LB
recording (Figure 8D). This supports the anatomic
finding of complex fascicular interactions. The
mechanism of the arrhythmia in this case was also
deemed to be focal LSF firing. Although Talib et al.
(21) has described verapamil-insensitive non–re-
entrant focal fascicular tachycardias, the present case
was not consistent with the previously described
findings. The proximal mid-septum is an area known
to be prone to activation delays. This is most pro-
nounced in the region where the LB divides into the
LAF, LPF, and LSF (3). The present authors postulated
that focal firing in the LSF would block anterograde
LSF conduction but allow for retrograde alternate
activation of the LAF and LPF.
This series illustrates circuits that involve retro-
grade conduction over the LSF and anterograde acti-
vation of the LAF and LPF. Several important clinical
features should be emphasized (Central Illustration).
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F I G U R E 9 Case 5: Surface and Intracardiac Recordings of the Clinical Arrhythmia

(A) Surface 12-lead electrocardiogram of the clinical PVC. (B) An activation map of the LV during the clinical PVC. A duodecapolar catheter is positioned along the mid-
septum where LSF potentials were recorded. During the clinical PVC, the LSF potentials were pre-systolic and followed an eccentric activation pattern suggesting early
activation along the LSF. (C) The earliest local potential at the LSF was targeted with ablation resulting in immediate suppression of the clinical PVC Abbreviations as in
Figures 1 to 3.

First, involvement of the septal fascicle as being part
of the circuit should be suspected in a patient who
presents with multiform fascicular
arrhythmia that each fit a fascicular pattern, especially
if accompanied by periods of narrow complex tachy-
cardia at the same rate. EP studies require the use of a
multipolar electrode catheter to record the activation
course of the LSF, LAF, and LPF both during sinus
rhythm as well as during tachycardia. While the LAF
and LPF can be well-delineated during EP studies, the
LSF was defined as a sequence of potentials recorded
between the areas of the LAF and LPF. Finally, one
should recognize the importance of entrainment
mapping of the LSF to prove its involvement (7,11).
STUDY LIMITATIONS. This study is limited by the
lack of simultaneous recording from all fascicular
episodes of areas during tachycardia. Sequential recordings may
be limited by either hemodynamic instability and
difficulties in provoking specific QRS forms. Entrain-
ment of the LSF to prove participation in the circuit
was not available in most of our patients due to the
catheter stability, which resulted in activation of the
contiguous myocardium and “bump” termination of
the arrhythmia. Furthermore, intracardiac echocar-
diography was not regularly used in this series.
Presently, it is appreciated that in some patients, the
“septal” fascicle is a hypothetical construct and may,
in fact, represent branches of the LAF and LPF. Even
JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 7, NO. 7, 2021 Sanchez et al. 869
JULY 2021:858–70 Arrhythmias of the Left Septal Fascicle

C ENTR AL I LL U STRA T I O N Features of Left Septal Fascicular Involvement

1. Multiform Fascicular 2. Narrow QRS Complex

Arrhythmias Ventricular Arrhythmia
I
I V1 V1 I V1
II
II V2 V2 II V2
Surface V3 III V3 III V3
III
ECG aVR aVR aVR
V4 V4 V4
aVL V5 aVL V5 aVL V5

aVF V6 aVF V6 aVF V6

LPF pattern LAF pattern

Activation LB LB
LB
Pattern RB RB RB
LAF LAF LAF

LSF LSF LPF LSF

LPF LPF

Earliest activation

Sanchez, J.M. et al. J Am Coll Cardiol EP. 2021;7(7):858–70.

(Upper) Clinical features suggestive of the LSF as a critical component of the arrhythmia circuit include the presence of: 1) multiple fascicular episodes of
arrhythmia with an LPF and LAF pattern; and/or 2) a narrow QRS complex ventricular arrhythmia. (Lower) Schemas of the activation pattern in the tri-
fascicular system. Red stars show the earliest activation. LAF ¼ left anterior fascicle; LPF ¼ left posterior fascicle; LSF ¼ left septal fascicle.

so, this would not negate our findings and results of
ablation.
CONCLUSIONS
Life-threatening fascicular episodes of arrhythmia
may occur in patients without structural heart dis-
ease. This paper presents 5 cases of fascicular epi-
sodes of arrhythmia that are best explained by
invoking the LSF as a critical component of the
arrhythmia circuit. High suspicion for the involve-
ment of LSF relied on the presence of multiform
fascicular episodes of arrhythmia (and/or narrow QRS
complex ventricular episodes of arrhythmia) and by
analysis of the activation pattern of fascicular
conduction during sinus rhythm and tachycardia.
Finally, the authors emphasize careful mapping of the
LAF, LPF, and the mid-septum for the LSF in order to
accurately define the arrhythmia circuit and deliver
successful ablative therapy.
FUNDING SUPPORT AND AUTHOR DISCLOSURES
The authors have reported that they have no relationships relevant to
the contents of this paper to disclose.
ADDRESS FOR CORRESPONDENCE: Dr. José M.
Sanchez, University of Colorado, 12401 East 17th
Avenue, Mailstop B-132, Aurora, Colorado 80045,
USA. E-mail: jose.4.sanchez@cuanschutz.edu.
870 Sanchez et al. JACC: CLINICAL ELECTROPHYSIOLOGY VOL. 7, NO. 7, 2021

Arrhythmias of the Left Septal Fascicle JULY 2021:858–70

PERSPECTIVES

COMPETENCY IN MEDICAL KNOWLEDGE: The LSF
consists of an arborized network of Purkinje fibers along
the left ventricular septum that is prone to conduction
slowing and tachycardia. Fascicular tachycardias that rely
on the LSF are challenging to identify, and in this series, 5
cases are presented of fascicular episodes of arrhythmia
that are best explained by involvement of the LSF as a
critical component of the arrhythmia circuit. We empha-
size the importance of multiple fascicular patterns as a
clue to suspect the LSF and the importance of careful
mapping of the trifascicular system.
TRANSLATIONAL OUTLOOK: This case series de-
scribes fascicular episodes of arrhythmia that have been
postulated to involve the LSF. The LSF is characterized by
a significant reduction in conduction velocity attributed to
regional distribution of gap junctions and load mismatch
caused by intense branching of Purkinje fibers. Presently,
it is appreciated that the LSF is a hypothetical construct
and may, in fact, represent branches of the LAF and LPF.
Further studies will be required to define the involvement
of the septal Purkinje fibers in arrhythmogenesis.

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