571

Mechanisms of Idiopathic Left Ventricular Tachycardia

BRUCE B. LERMAN, M.D., KENNETH M. STEIN, M.D.,
and STEVEN M. MARKOWITZ, M.D.
From the Departtnent of Medicine, Division of Cardiology. The New York Ho.spital-Cornell
University Medical Center, New York, New York

Idiopafhic Left Ventricular Tachycardia. Idiopaihic left ventricular tachycardia

(ILVT) difiers from idiopathic right ventricular outflow tract (RVOT) tachycardia with respect
to mechanism and pharmacologic sensitivity. ILVT can he categorized into three suhgroups.
The most prevalent form, verapamil-sensitive intrafascicular tachycardia, originates in the re-
gion of left posterior fascicle of the left hundle. This tachycardia is adenosine insen.sitive. demon-
strates entrainment, and is thought to he due to reentry. The tachycardia is most (»ften ahlated
in the region of the posteroinferior interventricular septum. A second type of ILVT is a form
analogous to adenosine-.vews/f/ve RVOT tachycardia. This tachycardia appears to originate from
deep within the iuterventricular septum and exits from the left side of the septum. This form of
VT also responds to verapamil and is thought to he due to cAMP-mediated triggered activity. A
third form of ILVT is propranolo) sensitive. It is neither initiated or terminated hy programmed
stimulation, does not terminate with verapamil, and is transiently suppressed by adenosine, re-
sponses consistent with an automatic mechanism. Recognition of the heterogeneity of ILVT and
its unique characteristics should facilitate appropriate diagnosis and therapy in this group of
patients. (J Cardiovasc Electrophysioi, Vol. 8, pp. 571-583, May 1997)

ventricular tachycardia, triggered activity, adenosine, ablation

Introduction tract (RVOT). In general, idiopathic left ventricu-

lar tachycardia differs from that originating from
Sustained monomorphic ventricular tachycardia the right ventricle wilh respect to mechanism, phiir-
(VT) is most often related to a myocardial struc- macologic responses, and treatment.
tural abnormality. However, no anatomic detect
The intent of this review is to sutnmari/e the
is identified in approximately 10% of patients who
clinical characteristics, mechanisms, and treatment
present for clinical evaluation: VT in these cases
of idiopathic monomorphic left ventricular tachy-
is therefore refeired to as idiopathic. During the
cardia. We have classified this fonn of VT into
last 15 years, a number of discrete forms of idio-
three subgroups: intrafascicular (verapatnil sensi-
pathic VT have been recognized. Nearly 80% of
tive), adenosine sensitive, and automatic (propra-
idiopathic VT originates from the right ventricle,
nolol sensitive) (Table 1).
most commonly fixim the right ventricular outflow
Verapamil-Sensitive Intrafascicular Tachycardia
This work wa.s supported in part by Grunt R0144747 from the Na-
tional Institutes of Health, the Rosenteld Hean Fotinduiioti. and
the Michael Wolk Hean Fciiindation. Dr. Lemian is an Established Clinical Characteristics
Investigator ot the American Heart Association.

Based on Cardiustim '96 presentation. Niee. Fratice. June 1996.

Address for correspondence: Bruce B. Lerman, M.D., Division of
Cardiology. New York Hospital-Cornell Medical Center, 525 Ea.st
68th St.. Starr Pavilion. 4th Hoor. New York, NY H)O2I. Fax:
212-746-8451: E-mail: blerman@med.comell.edu
Manu.script received 27 Augu.st 1996; Accepted for publication 21
November 1996.
The most common form of idiopathic left
ventricular tachycardia is verapamil-sensitive in-
trafascicular tachycardia. This usually originates
in the tegion of the left posterior fascicle and lias
a characteristic right bundle branch block (RBBB),
left supetior axis morphology. This fonn of idio-
pathic left ventricular tachycardia was first rec-
572 Journal of Cardiovascular Electrophysiology
Classification of Idiopathic Left Ventricular Tachycardia
lnlr:ila.scicular
(Vt'ruptimil Sen.sitivc)
Cluiractcri/ation linral'iiscictilar
Induction Progiammeti stiiniilation
+ / - caiecholamines
Morphology RBBB. L. superior axis;
RBBB, R. inferior axis
Origin L. posterior fascicle or
L. anterior fascicle
Entrdinment -I-
Mechanism Reentry
Propranolo!
Adenosine
Verapamil
L - left; LV = left ventricle; R = right; RBBB = right hundle branch block: RMVT = repetitive monomorphic ventricular
tachycardia; TA = triggered activity; + = present/sensitive: — = not present/insensitive.
ognized as an electrocardiograph ic entity in 1979
by Zipes et al.,' who identified the characteristic
diagnostic triad: (1) induction with atrial pacing;
(2) RBBB. left-axis configuration; and (3) mani-
festation in patients without structural heart dis-
ease. In 1981. Belhassen and coworkers^ were the
first to demonstrate verapamil sensitivity of the
tachycardia, the fourth identifying feature.
Fascicular tachycardia usually presents in pa-
tients between !5 and 40 years of age (range 7 to
65).^*'^ Approximately 6()% to 80% of patients are
men. The resting ECG in most patients is normal,
but nonspecific transient infeiolateral T wave
changes may be present after cessation of tachy-
cardia.^^^'- Coronai7 anteriography is normal in
these patients, as is ventricular function. Intriifas-
cicular VT can be incessant and may cause a re-
versible tachycardia-related cardiomyopathy.*^ Sym[>
toms during tachycardia include palpitations, dizzi-
ness, presyncope, and syncope. Sudden cardiac
death is not usually asscxriated with this form of
VX but at least one putative case has been reixsrted.'
Intrafascicuiar VT was originally described as
occurring at rest, but in recent years sensitivity of
the tachycardia tt) catecholamine stimulation (e.g.,
exercise or post exercise) or emotional distress has
been appreciated.'-'^ Images of Citrdiac sympathetic
innervation with I'-'l] tneta-iodobenzylguanidine
(MIBG) in patients with fascicular tachycardia are
usually unremiukable, suggesting thatregionalmyo-
cardial detiervatit)n is not responsible for cate-
cholamine sensitivity in this tachycardia.'-*
VT has an RBBB. left superior axis moq^hol-
ogy in 90% to 95% of patients, suggesting a site
of origin in the region of the left posterior fasci-
Vol. 8, No. 5, May 1997
TABLE I
.\uloiiialic
Adenosini- Sensitive (Propranolol S
11) Hxcrcisi; (I) iixercisL' induced
(2)RMVT (2)Incessant
Programmed stimulation Catec hula mines
+ / - ciUecho I amines
RBBB, inferior axis; RBBB. inferior/.'iiiperior axis;
RBBB. superior axis Polymorphic
LV septum LV
cAMP-mediated TA Enhanced automaticity
Teniii nates/transient
suppression
Transient suppression/
no effect
cle, near the posteroapical left ventricular sep-
tum. The remainder of patients present with an
RBBB. right inferior axis VT that originates in the
region of the left anterior fascicle, near the an-
terosuperior left ventricular septum." Unlike VT
associated with stRictural heart disease, which is
often associated with an RS interval > UK) msec
in the precordial leads, the RS interval during in-
trafascicular tachycardia is 60 to 80 msec and the
QRS duration is < 140 msec."
There is no single consistent histologic finding
in these patients. Left ventricular biopsy samples
obtained in 11 patienls showed nonnal findings in
3 patients and mild-to-moderate fibrosis and/or fat
infiltration in 8 patients. Two of these patients also
had iymp(X'ytic infiltration. Tlie latter finding is con-
sistent with evidence for healed myocarditis."" The
significance of these findings remains sjx'culative.
Signal-averaged ECGs analyzed in the time do-
main are normal wilh respect to the filtered QRS
duration, low-amplitude signal duration ( < 40 /7V).
and root mean square voltage during the lasi 40
msec of the filtered QRS complex.'' However, in
some of these same patients, high-fret|uency signals
are detected in tlie tenninal ptxtion of the QRS ct)in-
plex using spectral techniques, a finding that ap-
pears to correlate with fibrosis or fat on mytx'ardial
biopsy and fractionated clectiograms (lasting < 100
msec) localized to the left ventricular apex.'"'
Anatomic Substrate
The anatomic basis for this iinhythmia has pro-
voked considerable interest. Endocardial activation
mapping during VT identifies the earliest site in the
 Lerman, et al. Idiopathic Left Ventricular Tachycardia
region of the posteroapical left ventricular sep-
lum. This finding, along with the tachyctirdia's char-
acteristic QRS morphology during VT and short
retrograde VH intei-val. suggests a lefl posterior fas-
cicuiar origin. Further evidence points to an origin
within tlie Purkinje fiber network in the left poste-
rior fascicle. Nakagawa et al.'- recorded a high-fre-
quency potential preceding the site of earliest
ventricular activation during VT and sinus rhythm.
These potentials are thought to represent activation
of Purkinje fibers and are recorded from the pos-
terior one third of the left ventricular septum.
Successful ablation is achieved at sites where the
Purkinje potential is recorded 30 to 40 msec before
the VT QRS complex., suggesting that the tachy-
caidia originates from this or contiguous tissue.
Other data suggest that the tiichycardia may orig-
inate from a false tendon or fibromuscular band
that extends from the posteroinferior left ventri-
cle to the basal septum (Fig. 1).'**-" Surgical ex-
tlipation of the false tendon with either laser pho-
ttxdugulation"^ or resection iind cryoablation of the
myocardial attachment''' eliminates tachycardia.
Histologic examination of the resected false ten-
don disclosed abundant Purkinje fibers that were
oriented longitudinally with the long axis of ten-
don and which inserted into the endocardium.'**
Evidence suggests that false tendons are pres-
ent in a much higher percentage of patients with
left posterior fascicular tachyciirdia than in those
studied from a control group referred for echo-
Figure 1. Two-dimensional echocardiogram from a patient
with verapamii-sensitive intrafascicular tuchycardia. The
heart is seen in the parasternal long-axis view. Arrows
point to the false tendon. Ao - aorta: LA - left atrium: LV
= left ventricle: RV = right ventricle. (Reproduced with
permission from Thakur RK. Klein GJ. Sixaram CA. et at:
Anatomic substrate for idiopathic left ventricular tacliycar-
dia. Circulation 1996;93:497-5OL)
573
cardiography. Thakur et al.-" identified a false ten-
don extending from the posteroinferior left ven-
tricular free wall to the left ventricular septum in
15 of 15 patients with intrafascicuUir tachycardia.
In comparison, only 5% of 671 control patients
demonstrated a false tendon. It has therefore been
hypothesized that the false tendon composes part
of the tachycardia circuit or, alternatively, that the
tendon elicits stretch on Purkinje fibers in the left
ventricular septum.
Several issues remain with respect to the phys-
iologic significance of false tendons. For instance,
ablation at the site of attachment of the false icn-
don has not been demonstrated to be a requirement
for success. Furthermore, the specificity of iden-
tiiy'ig false tendons is unclear, since another study
confirmed the presence of false tendons witli irans-
esophageal echocardiography in 17 of 18 patients
with intrafascicuUir tachycardia, but also identified
false tendons in 35 of 40 control patients.-'
Mechanism
Although debate has centered on whether in-
trafascicular tachycardia is reentrant or triggered,
an overwhelming body of evidence supports a lo-
calized reentnint mechanism. The size of the tachy-
cardia circuit is relatively focal since: (I) antero-
grade His capture occurs without perturbing the
tachycardia cycle length"*^; and (2) sinus beats and
ventricular extrastimuli can capture the ventricles
without resetting VT.^^ The His bundle is not a re-
quired component of the reentrant circuit, since a
retrograde His-bundle potential is often recorded
20 to 40 msec after emliest ventiicukir activation.^-*
VT is initiated with programmed atrial or ven-
tricular extrastimuli or burst pacing from either
site. Often times isoproterenol infusion alone or
during concurrent programmed stimulation facili-
tates induction, presumably by increasing the slow
inwiird calcium cuirent (vide infra). An inverse re-
lationship is observed between the coupling in-
terval of the initiating extrastimulus and the ven-
tricular echo beat (fn^st beat of VT).^^'''" In most
cases, ventricular electrograms are discrete dur-
ing both sinus rhythm and tachycardia. Presystolic
activity typically tK'curs within 40 msec of the sur-
face QRS during VT.'"'^ Recent studies have, how-
ever, recorded continuous diastolic activity or mid-
diastolic potentials during VT at the ablation site.''
These potentials were likely related to the reen-
trant circuit, since tennination of the tachycaidia
was preceded by sptintaneous cessation of the con-
tinuous diastolic activity. The origin of fraction-
574 Journal of Cardiovascular Electrophysiology Vol. 8, No. 5, May 1997

ated electrograms in patients with structurally nor-
mal hearts is unresolved, but anisotropic conduc-
tion in Purkinje fibers has been shown to give rise
to polyphasic, fragmented electrograms.--
Okumuia et al.-'•-•* made several fundamental
ob.servations regarding the nature of the tachycar-
dia circuit. They deinonstrated that the tachycar-
dia could be entrained, e.g., during pacing with
constant fusion the last captured electrogram was
entrained but not fused, there was progressive but
constant fusion with increased pacing rates, and at
increased pacing rates., the electrogram at the ear-
liest site of activation changed from oilhodromic
to antidromic capture. These observations are il-
lustrated in Figure 2.^ Note that pacing at 170/min
from the RVOT during VT captures the right ven-
triculiir apex antidmmically, with a stimulus to elec-
trogram interval of 70 msec; however, the earli-
est site of activation in the left ventricle (-20 msec)
is captured orthodmmically through a zone of slow
conduction, with a stimulus to electrogram inter-
val of 395 msec. The morphology of the left ven-
tricular eiectrogram during entrainment is identi-
cal to that during VT. whereas pacing frtini the
same site (RVOT) during sinus rhythm results in
a different electrogram morphology (compared with
VT) due to antidromic capture (Fig. 2, panel B).
As the pacing rate increases from 170 to 190/min,
there is also evidence for decremental conduction
within the region of slow conduction. At a pac-
ing rate of 20()/min. the interval from the pacing
stimulus to the last enlrained electrogram at the
site of eailiest activation in the lett ventiicle abmptly
decrea.ses to 100 msec, due to a change from or-
thodromic to antidromic capture.
The zone of slow conduction appears to be de-
pendent on the slow inward calcium current,
since the degree of slowing of VT cycle length in

190 bpm

Figure 2. Tracings from ECG lead V, and intracardiac electrograms recorded at the right ventricular outflow tract (RVOT),
right ventricular apex (RVA), and at an early activation site in the left ventricle (LV) during ventricular tachycardia (VT). (A)
Ventricular pacing at rates of 170, 180, 190, and 200 beats/min (bpm) from the RVOT entrained the tachycardia. Activation
time at the LV site relative to the onset of the QRS complex was -20 msec. (B) Ventricular pacing at a rate of 180 bpm from
the RVOT during sinus rhythm. See te.xt for discussion. All intei-vals are e.xpressed in milliseconds: circled values indicate
conduction times. S = stimulus artifact. (Reproduced by permission of the pubiisherfrom Okumura K, Yanmbe H. Tsuchiya T,
et al: Characteristics of slow ctmduction zone demon.strated during entrainment of idiopathic ventricular tachycardia of left
ventricular origin. Am J Cardioi, Vol. 77, pp. 379-383. Copyright 1996 by Excerpta Medico.)
 Lerman, et al. Idiopathic Left Ventricular Tachycardia 575

resix)nse to verapamil is entirely attributable to its
negative dromotropic effects on the area of slow
conduction. A lesser degree of slowing was ob-
served with lidcx-aine (Fig. 3).-'^ These data suggest
that the Purkinje fibers that make up the reentrant
circuit have piutially depoUuized resting membrane
potentials, with the depolarizing currents relatively
more dependent on the slow inwmd calcium cur-
rent than on depressed fast Na+ channels.
The entrance site to the zone of slow conduc-
tion is thought to be located at the base of the left
interventricular septum. This conclusion is based
on the compiuison of conduction times during pac-
ing from the right ventricular apex and outflow
tract to a site that exits from the area of slow con-
duction.-"* The conduction interval is significantly
shorter when pacing from the RVOT than from
the right ventricular apex, suggesting that the
RVOT is located closer to the entrance site of the
reentrant circuit. In contrast, the interval from the
exit site to the pacing site is shorter with respect
to the apex than the RVOT. suggesting that the
exit site is in the posteroapical region of the left
interventricular septum.-^ These data provide a
possible explanation for the observation that man-
ifest entrainment is more frequently acliieved when
pacing from the RVOT than from the right ven-
tricular apex. For example, pacing from a site
proximal to area of slow conduction, e.g.. the
RVOT in intrafascicular tachyciudia. facilitates fu-
sion during manifest entrainment. Fuithermore,
the relatively greater distance of the apex from
the entrance site compared with the outflow tract
decreases the likelihood of establishing entrain-
ment in the presence of a niirrow excitable gap.
Intrafascicular reentrant tachyciudia has a char-
acteristic electropharmacologic profile. Like
other forms of idiopathic VT it is responsive to
verapamil, but in contrast to VT originating from
the RVOT. which is thought to be due to cAMP-
mediated triggered activity, adenosine and Valsalva
maneuvers have no effect on this form of VT'*•-''-''
These respt^nses are useful for clinical and mech-
anistic distinctions between these two forms of id-
iopathic VT. They suggest that, although the sub-
strate for both tachycardias aie calcium dej^-ndent.
the reentrant tissue in intrafascicular tachycardia
appears to be primarily dependent on the basal
slow inward current in partially depolarized Pur-
kinje fibers. In contrast, RVOT tachycardia due to
triggered activity is dependent on intracelluhir cal-
cium overioad that is achieved through cAMP stim-
ulation and increased calcium channel conduc-
tance.-*^ Consistent with these considerations, adeno-

Basetine Lidocaine VerapamJl

500 msec

Figure 3. An example of the effects of lidocaine and verapamil on the conduction times measured during entrainment. ECG
leads I, II. and V, are shown along with electrograms recorded from the right ventricular outflow tract {RVOT) and right ven-
tricular apex (RVAj and from the proximal (LVp) and distal iLVd) pair <}f electrodes located cit the site of early activation in
the left ventricle. St-A (pacing interval from the RVOT stimulus to the site of early activation LVd) and St-B (pacing inten'al
from the RVOT stimulus to the RVA) were 475 and 60 msec at baseline. 490 and 60 msec after lidocaine. and 560 and 60
msec after verapamil, re.spectively. All numbers are in milliseconds: circled values indicate conduction times. S = stimulus ar-
tifact. (Reproduced by permission of the publisher from Okumura K. Yamahc H. Tsuchiya T et at: Characteristics of slow
condiidion zone demonstrated during entrainment of idiopathic ventricular tachycardia of left ventricular origin. Am J Car-
diol. Vol. 77, pp. 379-383. Copyright 1996 by Excerpta Medica,)
576 Journal of Cardiovascular Electrophy.siology Vol. 8, No. 5. May 1997
sine (or ATP) was ineffective in 26 patients with
left intrafascicular tachycaidia, whereas verapamil
tenninated VT in 24 of these patients, which typ-
ically results in oscillation before termination.-^
Therapy
Although it is well established that acute treat-
ment of intrafascicular tachycardia with intravenous
verapamil is effective, there is relatively little data
available regarding efficacy of chronic antiar-
rhythmic therapy. The largest series is that reported
by Ohe et al." Twenty patients were treated with
verapamil (160 to 320 mg/day) and followed for
a mean of 6 years. Six of these patients also re-
ceived either prtK-ainanide, proprantjiol. or digoxin.
Fourteen patients had tachycaixlia classified as mcxl-
erately severe, defined by the degree to which
symptoms impeded daily activities, iind six patients
had VT classified as severe. In tlie moderately im-
paired group, symptoms were completely abolished
by verapamil in five patients and were markedly
improved in nine. In contrast, verapamil had no
influence on symptoms in the six patients who
were significantly impaired by their tachycardia.
Other classes of drugs, such as beta blockers and
Class I antiarrhythmics. are either ineffective or
partially effective. Of note. 14 patients who were
described as having mild symptoms during VT and
who were not treated and were followed for 1 to
10 yeai"s had either no progression or complete res-
olution of their symptoms.
Patients with intrafascicular VT associated with
presyncope or syncope, those with recurrent sus-
tained tachycardia, or those who are intolerant or
TABLE 2
Catheter Abialioti of Verapamil-Sen.sitive Left Intrafascicular Tachycardia
Successful Follow-Up
Study No. Pts. Ablation I months)
2/2 4-7
Nakagawa 8 7/8 !-67
Wen^" 20 17/20 i-23
Coggins^' 8 7/8 2-25
Kottkamp'^ 5 4/5 4^3
Zardini" 8 7/8 2-41
Total 51 44/51
(86%)
AR — aortic regurgitation; MR = mitral regurgitation.
resistant to antiarrhythmic therapy are appropri-
ate candidates for ablative therapy. The results of
radiofrequency ablation in this group of patients
are excellent, with outcomes similar to those
achieved with radiofrequency ablation for idio-
pathic RVOT tachycardia. Data from six studies
in which the ablative approach, long-temi results,
and complications are well described are summa-
rized in Table 2,^'^^^^-^^ Success is achieved in ap-
proximately 85% of patients; two complications
have been reported in 51 patients. One was mi-
tral regurgitation due to a tom chorda that resulted
from entrapment of the ablation catheter in a clujrda
of the mitral leatlet.'- The other complication
was aorticregurgitationthat presumably developed
secondary to the retrograde aortic approach used
for ablation."
Multiple strategies have been deployed to iden-
tify the appropriate site for ablation. Initial ap-
proaches used pace and activation mapping. Con-
cordance in QRS morphology between the 12-lead
ECG during VT and pace mapping, and local ven-
tricular activation that preceded the surface QRS
complex by > 30 msec were considered effective
criteria.^" However, a number of unsuccessful ab-
lative sites have "perfect" matches between the
pace map iuid VT. One explanation for this phe-
nomenon is that, during pacing, there may be cap-
ture of the Purkinje network of the posterior fas-
cicle, not all of which makes up the tachycardia
circuit. Activation during pacing of components of
the Purkinje network in this region that arc not part
of the reentrant circuit may result, however, in a
pattem of ventricular activation similar to that which
occurs during VT.
Cniiiiiit'iit.s
Nunc Ciuided by p;ice map and venlrii.ular act
mapping (> M) msec before surlate
1/8 (MR) Ciuided by earliest Purkinje liber potential (P)
during venlricular lachycardia
None Purkinje fiber poieniials were not considered
specific tor identifying successful ablation
sites
1/H(AR) Guided by pace and ventricular activation
mapping
None Continuous diastolic or mid-diastolic activity
during VT
None Radiofrequency energy (3 patients): direct
current shock [5 patienls)
2/51
(4%)
 Lerman. et at. Idiopathic Left Venlricular Tachycardia
Other investigators have emphasized the im-
portiuice of recording a brief, high-frequency po-
tentiiil that precedes earhesl ventricular activation
in the region of the left posterior fascicle.'- Since
this potential is also present during sinus rhythm
and precedes ventricular activation., it is thought to
represent activation of the Purkinje network of the
left posterior fascicle (Fig. 4). TTiese potentials are
rectirded over a 2- lo 3-cm- areii in the posterior as-
pect of the left ventricular septum. 25% to 30% of
the distance between apex and base. Pacing from
the site of the high-frequency potential results in a
pacing stimulus-QRS interval identical to the high-
frequency potential-QRS interval duiing VT. Ra-
diofrequency energy directed at the earliest (30 to
40 msec before the surface QRS) high-fiequency
presystolic activation (F\irkinje potential) effectively
Sinus Rhythm
Figure 4. P potentials recorded during ventricular tachy-
cardia and sinus rhythm at a successfut ablation .site. Dur-
ing ventricutar tachycardia (VT, teft panet), a discrete po-
tential (P) was recorded preceding ventricular activation
from the left ventricular septum (LV). The left panel shows
early retrograde conduction to the His bundle (QRS-H. 5
msec), followed by anterogrude activation of the proximal
right bundte branch (RB). During sinus rhythm (right
panei), the recording from the left ventricutar electrogram
at the same site demonstrates a distinct potential (P), which
was recorded after the His-bundle potential (H) and before
the onset of tiie QRS complex, consistent with activation of
a distal component of the teft bundle branch .system. A =
atriat potentiai: V = ventricular activation. (Reproduced
with permission from Nakagawa H, Beekman KJ, McClel-
land JH. et al: Radiofrequency catheter ablation of idio-
pathic left ventricular tachycardia guided by a Purkinje po-
tential. Circulation 1993:88:2607-2617.)
577
temiinates VT and precludes its reinduction.'' Ab-
lating at the site of the earliest Purkinje potential
appears to be a more critical determinant of suc-
cess than the earliest site of ventricular activation.
Furthermore, the site of earliest Purkinje potential
is often remote (> 1 cm) from the site of earliest
ventricular activation (Fig. 5).'-
Not all investigators agree with this ap-
proach. ^"•^'-'' Wen et al.^ argue that these poten-
tials are recorded in control patients, and that the
potentials do not disappear after successful abla-
tion. Recording Purkinje potentials in control pa-
tients should not be surprising. However, the per-
sistence of these potentials after successful abla-
tion is more problematic and suggests that our
understanding of the significance of these poten-
tials is incomplete.
Interfascicular Tachycardia
Although electrophysiologicatly distinct but
anatomically related to intrafascicular tachycardia,
inletfiisciciilar tachycatxiui confined to the left ven-
tricle should be considered in the differential di-
agnosis of idiopathic left ventricular tachycardia."-'^
There is not yet sufficient data to detemiine whether,
similar to bundle branch reentry, conduction dis-
ease and dilated cardiomyopathy are associated
conditions, although RBBB and tin jinterior or pos-
terior fascicukir block are often present during si-
nus rhythm. Tlie reentrant tachycardia circuit in-
volves anterograde conduction over the left ante-
rior or posterior fascicle with the retrograde limb
comprised of the alternative fascicle. Therefore,
tachycardia with an RBBB. left posterior fascicu-
lar block would indicate anterograde conduction
over the left anterior fascicle and retrograde con-
duction over the left posterior fascicle. Criteria re-
quired to diagnose left interfascicular tachycardia
include: (1) RBBB moiphology during tachyciir-
dia, which is similar to that recorded in sinus
rhythm: (2) reversal in activation sequence of the
His and left bundle (LB) potentials during tachy-
cardia; (3) an HV interval shorter during VT than
sinus rhythm; (4) spontaneous oscillations of tachy-
cardia cycle length due to changes in the LB-LB
interval that precede and drive the ventricular cy-
cle length: and {5) termination of tachycardia with
venlricular extrasllmuli or radiofrequency ablation
that produces block in either of the two fascicles.
Adenosine-Sensitive VT
Adenosine-sensitive VT most commonly orig-
inates from the RVOT Increasingly, however,
578 Journal of Cardiovascular Electrophysiology Vol. 8. No. 5. May 1997

A. Unsuccessful Ablation Site B. Successful Ablation Site

100 msec

Figure 5. Comparison of electrograms between successful and imsucce.-isful abtalion sites. (A) Tiie lefi ventricular electro-
gram shows a P potential preceding ihe QRS by 25 msec, which fuses with the local ventricular potential (V). This was the
earliest ventricular potential recorded during mapping and preceded the QRS hy 18 msec. Ablation at this site was unsuccess-
fui. (B) The left ventricular electrogram recorded the earliest P potential (P-QRS. 40 msec}. Ahhitinn at this .site was .uiccess-
Jul, even though the timing ofthe local ventricular potential was later than in A (V-QRS. 12 m.tec). (Reproduced wilh perm is-
sion from Nakagawa H. Beckman KJ, McClelland JH, ei al: Radiofrequency catheter ablation of idiopathic left ventricular
tachycardia guided by a Purkinje potential. Circulation 1993:88:2607-2617.)

ants of this form of arrhythmia, originating from
the left ventricular outflow tract, have been iden-
tified. In our series of patients with adenosine-sen-
sitive VT, 10% have a left ventricular origin of
tachycardia. Compelling laboratory and clinical
data support the concept that termination of idio-
pathic VT with adenosine is consistent with a
cAMP-mediated triggered mechanism.^*^' Reasons
for adenosine's lack of effect in catecholamine-me-
diated VT due to reentry and automaticity have
been addressed in a previous publication from our
laboratory.-'*
Adenosine-sensitive VT results from cAMP-
stimulated intracellular calcium overload. This
results in an oscillatory release of calcium from
the sarcoplasmic reticulum, resulting in a triinsient
inward current (I-n) and a delayed afterdepolariza-
tion (DAD) due to Na*-Ca-+ exchange.-^** Adeno-
sine's cellular electrophysiologic effects in the ven-
tricle and Purkinje fibers are due to cAMP antag-
onism. This effect is mediated by the inhibitory G
protein G,. which is coupled to the surface mem-
brance adenosine A|-receptor. After binding to the
activated receptor and exchanging guanosine
triphosphate (GTP) for guanosine diphosphate
(GDP), the G protein, a heterotrimer, dissociates
into GTP-a and 0y complexes. Either of these
complexes can abolish the stimulatory effects of
cAMP on the slow-inward current I^a and l-^^-
The clinical diagnosis of triggered activity is
also supported by tennination of VT witli Valsalva
maneuvers, carotid sinus pressure, or edrophonium.
verapamil. and beta blockade.^'**''" The effects of
increased vagal tone are mediated by the same sig-
nal tranduction cascade described for adenosine.
following binding of acetylcholine to the M^ nius-
carinic cholinergic receptor.-" In addition, the tachy-
cardia is initiated and tenninated with programmed
stimulation, and concealed and manifest enlrain-
ment cannot be demonstrated from multiple pac-
ing sites. A left ventricular origin is suggested by
an RBBB VT morphology in lead V, or a left bun-
dle branch block (LBBB) morphology associated
with an early precordia! transition (V,).
Failure to recognize that this arrhythmia can
originate from the left ventricle and confusion re-
garding the cellular mechanisms of adenosine's ef-
fects can lead to an erroneous diagnosis of clini-
cal mechanism.*"^ There are two common points of
misinterpretation: (1) adenosine's antiadrenergic
electrophysiologic effects are mediated by mech-
anisms independent of inhibition of adenylyl cy-
clase; and (2) adenosine tennination of isopro-
terenol-independent VT indicates that adenosine
acts by a catecholamine-independent mechanism.
Confusion regarding the first point relates to data
on the cAMP-independent eftects of adenosine on
the contractile protein phospholamban-"^ and one
unconfirmed report showing that adenosine de-
creases affinity of the /3-receptor for its agonist."'''
These data do not pertain to adenosine's electro-
physiologic effects, however. We have previously
shown that adenosine abolishes the effects of
forskolin, an adenylyl cyclase activator (that acts
 Lerman, et al. Idiopathic Left Ventricular Tachycardia 579

independently of/3-receptor activation), which in-
creases cAMP, IQ,,,^,, and I^ and induces DADs and
triggered activity. The inhibition by adenosine of
forskolin's electrophysiologic eflects are abolished
by pertussis toxin. Pertussis toxin inactivates G^
through ADP ribosylation, thereby blocking adeno-
sine's inactivaiion of adenylyl cyclase. Further-
more, adenosine fails to abolish DADs and trig-
gered activity elicited by dibutyryl cAMP.-^'' These
data unequivocably demonstrate that adenosine's
electrophysiologic effects on triggered activity are
mediated by an antiadrenergic process, one that
is mediated at the level of adenylyl cyclase.
TTie second point is a source of frequent con-
fusion. We have previously demonstrated that, al-
though iHipetitive monomorphic VT (RMVT) is an
arrhythmia that occurs at rest and does not require
exogenous catecholamine infusion for its induc-
tion, it is cAMP-mediated tachycardia since it ter-
minates in response to beta blockade and edro-
phonium. Furthermore, it is too simplistic to as-
sume that because an arrhythmia does not require
exogenous catec ho famines for initiation, it is not
cAMP mediated. We have shown, for example,
that sedentary patients with RMVT have tran-
sient subclinical increases in sympathetic tone that
precede VT. inferred from analysis of heart rate
variability."'
The clinical and electrophysiologic characteris-
tics of the four patients in our series with adeno-
sine-sensitive left ventricular tachycardia are sum-
marized in Table 3. A left ventricular site was con-
firmed by activation and pace mapping studies and
the site of successful radiofrequency ablation in
three patients. Thens were two men and two women
between 17 and 64 years old. No patient had stnic-
tural heart disease. VT was initiated in all patients
with burst pacing from the right atrium and/or
the right ventricle. Isoproterenol facilitated initia-
tion of VT in three patients.
Several points are noteworthy. (I) Two pa-
tients had a VT configuration simulating verap-
amil-sensitive intrafascicular reentry. However,
entrainment criteria could not be demonstrated
despite pacing from the right ventricular apex,
outflow tract, and left ventricular apex, and tbe
tachycardia was sensitive to adenosine and ve-
rapamil and responsive to vagal maneuvers (Figs.
6 and 7). Adenosine-sensitive VT with an RBBB.
left superior axis thought to be due to triggered
activity has also been identified by others.'*^ There-
fore, termination of suspected intrafascicular
tachycardia with adenosine should raise the pos-
sibility of cAMP-mediated triggered activity. (2)
The tachycardia can originate from the superior
basal region of the left interventricular septum,
near the area of the RVOT.**^ In one patient (pa-
tient 3. Table 3), VT had an LBBB. left inferior
axis morphology. It was initially mapped to the
septal region of the RVOT and was confirmed
by pace mapping. The tachycardia was not suc-
cessfully ablated from the RVOT with radiofre-
quency energy. Since VT showed an early pre-
cordial R wave transition in lead V,, the left side
of the interventricular septum was mapped
through a retrograde approach. An early site of
activation as well as a good correlation be-
tween the pace map and VT was identified in
the left ventricular outflow tract. Ablation at this
site tenninated VT and has rendered the patient
symptom-free for 2 years. Another patient with
an RBBB. right inferior axis morphology during
VT was also ablated in this region (patient 2.
Table 3). During VT, there was an RBBB con-

TABLE 3
Clinical Characleristics of Adenosine-Sensitive Left Ventricular Tachycardia
CSP/
Cardiac VI VT CL Valsalva/
No. Age/Sex Diagnosi!i Initiation (msec) Morphiilot>y Adeniisinc Verapamil Kdrdphiiiiiuni
1 17/M Normal ISO. RAP, 420 RBBB. righl + +
RVP. VES superior axis
2 64/F Normal RAP. RVP, 510 RBBB. right + + +
ISO + Amino inferior axis
+ Atropine
3 63/F Normal RVP 410 LBBB.* left + + -f-
inferior axis
4 20/M Normal RAP, RVP + ISO 290 RBBB. right + +
superior axis
Amino = aniinophylline; CL = cycle length: CSP = carotid sinus pressure; F = female; ISO = isoproterenol; M = male;
RAP = rapid atrial pacing; RBBB= right bundle branch block; RVP = rapid ventricular pacing; VT = ventricular
tachycardia; + = sensitive; — - insensitive.
^Successful ablation was achieved from the left side ofthe interventricular side.
580 Journal of Cardiovascular Electrophysiology Vol. 8. No. 5. May 1997

A.

B. ISOPROTERENOL, 8

1000 msec

Figure 6. Initiation of adenosine-sensitive left ventricular tachycardia. Surface ECG leads I, aVF. and V, and intracardiac
recording from the right venlricular apex (RVA) are shown. (A) Ventricular tachycardia is initiated with a .single ventricular
extrastimulus. The extrastimulus is introduced 330 msec after an eight-heat drive at 500 msec. This rhythm, although likely
due to cAMP-mediated triggered activity, can be confused with verapamil-sensitive intrafascicular tachycardia in that it has
right hundle branch hlock. superior axis configuration, and is initiated with programmed stimulation in a patient without
structural heart disease. Bar represents WOO msec. See text for further di.scussion. fB) Initiation of the patient s clinical
tachycardia with isoproterenol. S = stimulus; V = ventricular potential. (Reproduced with permission from Lernuin HB: Re-
sponse of nonreentrant catecholamine-mediated ventricular tachycardia to endogenous adenosine and acetylcholine: Evi-
dence for myocardial receptor-mediated effects. Circulation 1993:87:382-390.)

figuration in lead V, and positive concordance
in ihe precordial leads (Fig. 8). The fluoroscopic
position of the ahlation catheter at the site of suc-
cessful ablation is shown in Figure 9.
In addition, we have identified four addi-
tional patients with adenosine-sensitive VT who
presented with hoth LBBB and RBBB VT
(each with an identical axis). These data suggest
that, in these cases. VT originates from a single
focus in the interventricular septum and exits to
the epicardium, either to the right or left side of
the septum.

A. ADENOSINE, 225

B. VERAPAMIL, 10

1 sec

Figure 7. Re.sponse of adenosine-sensitive left ventricular tachycardia to adenosine and blockade of slow inward calcium
current (same patient as shown in Fig. 6). Surface ECG lead V, is shown. (A} Adenosine terminates ventricutar tachycardia 9
.seconds after holus administration. (B) Verapatnil terminates ventricular tachycardia within 60 .seconds of administration.
See text for discussion. Bar represents I second. (Reproduced with permission from lA-rman BB: Response of nonreentrani
catecholamine-mediated ventricutar tachycardia to endogenous adenosine and acetylcholine: Evidence for myocardial recep-
tor-mediated effects. Circulation 1993;87:382-390.)
 Lennan. et al. Idiopathic Left Ventricular Tachycardia 581

VT

n
A

PACE MAP

B = I sec

Figure 8. Comparison of ventricutar tachycardia (VT) and pace map morphologies (the latter from the left ventricular out-
flow tract) in a patient with adenosine-sen.sitive VT. The site of the pace map was also the site of .successful ahlation (see Fig. 9).

Automatic (Propanolol-Sensitive) VT cardia is also transiently suppressed (up to 20 sec)

This tachycardia presents most often in patients
without structural heiirt disease, in those under 50
years old. and is often precipitated by exercise.
The tachycardia may arise from either ventricle
and can present as monomorphic or polymorphic
VT. To date, there have heen no systematic stud-
ies on the demographic or functional myocardial
characteristics of these patients.
This form of VT is thought to represent adren-
ergically mediated automaticity because pro-
grammed stimulation cannot initiate or terminate
the arrhythmia, whereas the tachycardia is induced
with catechoUunines and is sensitive to beta block-
ade.^' The tachycardia is not likely due to abnor-
mal automaticity {resting membrane potential —
-60 mV) because calcium channel blockers are in-
effective.-*" and the rhythm does not demonstrate
acceleration during overdrive pacing. The tachy-
but not terminated by adenosine.''''"'
The cellular mechanism(s) governing this ar-
rhythmia iUid ihe anatomic substrate are poorly de-
lineated. However, since adenosine's effects on
adrenergically mediated automaticity arising
from Purkinje fibers depend on the resting mem-
brane potential, with greater effect observed at more
negative potentials ( 80 to -90 inV) and a Ies.ser
or no effect at more positive potentials, it is
likely that these automatic rhythms arise from cells
that are fully polarized.'** This is also consistent
with the clinical observation that automatic VT can
be transiently suppressed with overdrive pacing.
The membrane cuirent that most likely mediates
this arrhythmia in Purkinje fibers is the pacemaker
current 1,. This cation current is carried by Na* and
K*^ and is activated by hyperpolarization. Cate-
cholamines modulate the rate in automatic cells by
shifting the If activation curve such that If is acti-
582 Journal of Cardiovascular Electrophysiology Vol. 8. No. 5. Muy 1997
Figure 9. Anteroposterior (AP) ftuoroscopic image of the
catheter position in the left ventricular outflow tract (LVOT),
at the site of succes.sful radiofrequency ahlation in a patient
wilh adeno.sine-sensitive VT (same patient as shown in Fig.
8). Reference catheters are positioned in the region of the His
bundle (HBE) and right ventricutar outflow tract (RVOT).
vated at less negative membrane potentials.'***
Adenosine api^ars to attenuate I, through an an-
tiadrenergie mechanism.''^
Conclusion
Idiopathic VT is no longer a term that encom-
passes a poorly defined entity. Data accumulated
over the last 10 to 15 years have shown that this
type of tachycardia is actually composed of mul-
tiple discrete subtypes that are best differentiated
by their mechiuiism, VT morphology, site of ori-
gin, and responses to electropharmacologic probes.
Appreciation of these distinctions not only facili-
tates appropriate diagnosis and treatment but should
prompt in the next decade further investigation that
leads to a more complete understanding of the cel-
lular pathogenesis of the various forms of idio-
pathic VT. Once this goal is achieved, the desig-
nation "idiopathic" can be permanently removed.
References
1. Zipes DP, Foster PR, Troup PJ, et al: Atrial induction
of ventricular [achycardia: Reentry versus triggered ac-
tivity. Am J Cardiol 1979:44:1 -8.
2. BelhasscEi B. Rolmcnsch HH. Laniado S: Response of
recurrent sustained ventricular tachycardia to verapa-
niil. BrHeartJ l98l;46:679-682.
3. German LD, Packer DL, Bardy GH, et al: Venlricular
tachycardia induced by atrial stimulation in patients
without symptomatic cardiac disease. Am J Cardiol
1983:52:1202-1207.
4. Lin FC. Finley CD. Rahimtoola SH, et al: ldiupathie
paroxysmal ventricular tachycardia with a QRS pattem
of right bundle branch block and left axis deviation: A
unique Llinital entity with specific properties. Am J
Cardiol 1983;52:95-l'(X).
5. Ward DE. Nathan AW, Camm AJ: Fascicular tachy-
cardia sensitive to calcium antagonists. Eur Heart J
1984;5:896-905.
6. Klein GJ. Millman Pj. Yee R: Recurrent ventricular
tachycardia responsive to verapamil. PACE I984;7:
938-948.
7. Belhassen B. Shapira I. Pelleg A. et a!: Idiopathic re-
current sustained venlricular tachycardia responsive to
verapamil: An ECG-electrophysiologic entity. Am
Heart J 1984;IO8:1034-1037.
8. Jordaens L. Weync A, Clement D: Ventricular tachy-
cardia during exercise treated by verapamil. Int J Car-
diol 1986; 11:9-15.
9. Sethi KK. Manoharan S. Mohan JC. et al: Verapamil in
idiopathic ventricular tachycardia of right bundle
branch block moqiihology: Observations during electro-
physiologic and exercise testing. PACE l986;9:8-t6.
10. Ohe T. Shimomura K. Aihara N. et al: Idiopathic sus-
tained left ventricular tachycardia: Clinical and electrophy-
siologic characteristics. Circulation 1988:77:560-568.
I i. Ohe T. Aihara N. Kaniakura S, et ai: Long term out-
come of verapamil-sensitive sustained left ventricular
tachycardia in patients without structural heart disease.
J Am Coli Cardiol 1995:25:54-58.
12. Nakagawa H. Beekman KJ. McClelland JH, et al: Ra-
diofrequency catheter ablation of idiopathic left ven-
tricular tachycardia guided by a Purkinje potential. Cir-
culation 1993:88:2607-2617.
13. Kottkamp H. Chen X. Hindricks G. et al: Idiopathic
left ventricular tachycardia: New insights into electro-
physiological characteristics and radiofrequency cathe-
ter ablation. PACE I995:!8:128.S-I297.
14. Wharton JM, Eckart D. 1-riedman IM. ei al: Sympa-
thetic denervation relates to type of ventricular tachy-
cardia in patients with normal hearts. Circulation 1993;
88:1-116.
15. Andrade FT. Eslami M, Elias J, et al: Diagnostic clues
from the surface ECG to identify idiopathic (fascicular)
ventricular tachycardia: Correlation with etctrophysio-
logic fmdings. J Cardiovasc Electrophysiol 1996;7:2-8.
16. Morgera T. Salvi A. Alberti E. et al: Morphological
findings in apparenlly idiopathic ventricular lachycar-
dia. An echocardiographic hemodynamic and histo-
ioglc study. Bur Heart J 1985:6:323-3.34.
17. Kinoshita O. Kamakura S, Ohe T. et al: Spectral analy-
sis of signal averaged electrocardiogram in patients
with idiopathic ventricular tachycardia of left ventricu-
lar origin. Circulation 1992:85:2054-2059.
18. Gallagher JJ. Sclle JG. Sevenson RH, et al: Surgical treat-
ment of arrhythmias. Am J C£irdiol I988:61:27A-44A.
 Lerman. et al.
19. Suwa M. Yoneda Y, Nagao H. et al: Surgical correc-
tion of idiopathic paroxysmal ventricular tachycardia
possibly related to left ventricular false tendon. Am J
Cardiol 1989:64:1217-1220.
20. Thakur RK, Klein GJ. Sivaram CA. et al: Anatomic
substrate for idiopathic left ventricular tachycardia.
Circulation 1996:93:497-501.
21. Lin FC. Wen MS. Wang CC, et al: Left ventricular fi-
bromuscular band is not a specific substrate for idio-
pathic left ventricular tachycardia. Circulation 1996:
93:525-528.
22. Spach MS. Barr RC. Johnson EA: Cardiac extracellular
potentials: Analysis of complex wave forms about the
Purkinje nelworks in dogs. Circ Res 1973:33:465-473.
23. Okumura K. Matsuyama K. Miyagi H. et al: Entrain-
ment of idiopathic ventricular tachycardia of left ven-
tricular origin with evidence for reentry with an area of
slow conduction and effect of verapamil. Am J Cardiol
1988:62:727-732.
24. Okumura K, Yamabe H. Tsuchiya T, et al: Characteris-
tics of stow conduction zone demonstrated during en-
trainment of idiopathic ventricular tachycardia of left
ventricular origin. Am J Cardiol 1996:77:379-383.
25. Aizawa Y. Chinushi M. Kitiizawa H. et a!: Spatial tiri-
entation of the reentrant circuit of idiopathic left ven-
tricular tachycardia. Am J Cardiol 1995;76:316-319.
26. Ng KS. Wen MS. Yeh SJ. et al: The effects of adeno-
sine on idiopathic ventricular tachycardia. Am J Car-
tliot 1994:74:195-197.
27. Griffith MJ, Garratt CJ, Rowland E. et al: Effects of in-
travenous adenosine on verapamil-sensitive "idio-
pathic" ventricular tachycardia. Am J Cardiol 1994:73:
759-764.
28. Lennan BB. Stein KM. Markowitz SM: Adenosine-
sensitive ventricular tachycardia: A conceptual ap-
proach. J Cardiovasc Electrophysiol 1996:7:559-569.
29. Page RL. Shenasa H. Evans JJ, et al: Radiofrequency
catheter ablation of idiopathic recurrent ventricular
tachycardia with right bundle branch block, left axis
morphology. PACE 1993;16:327-336.
30. Wen MS. Yeh SJ. Wang CC. et al: Radiofrequency ab-
lation therapy in idiopathic left ventricular tachycardia
with no obvious structural heart disease. Circulation
1994:89:1690-1696.
31. Coggins DL. Lee RL. Sweeny J, et al: Radiofrequency
catheter ablation as a cure for idiopathic tachycardia of
both left and right ventricular origin. J Am Coll Car-
diol 1994:23:1333-1341.
32. Zardini M. Thakur RK. Klein GJ. et al: Catheter abla-
tion of idiopathic left ventricular tachycardia. PACE
1995;18:1255-I265.
33. Wellens HJJ. Smeets JLRM: Idiopathic left ventricular
tachycardia: Cure by radiofrequency ablation. Circula-
tion 1993:88:2978-2'979.
34. Crijns JJGM. Smeets JLRM. Rodriqiiez LM. et al:
Cure of interfascicular reentrant ventricular tachycar-
dia by ablation of the anterior fascicle of the left bun-
dle branch. J Cardiovasc Electrophysiol 1995:6:486-
492.
Idiopathic Left Ventricular Tachycardia 583
35. Simons GR. Sorrentino RA. Zimemian LL et al: Bundle
branch reentry tachycardia ;ind possible sustained interfas-
cicular reentry tachycardia with a shared unusual induc-
tion pattem. J Cardiovasc Electrophysiol 1996:7:44-.50.
36. Belardinelli L, Isenberg G: Actions of adenosine and
isoproterenol on isolated mammalian ventricular myo-
cytes. Circ Res 1983:53:287-297.
37. Song Y. Thedford S. Lerman BB. et al: Adenosine-
sensitive afterdepoiarizations and triggered activity in
guinea pig venlricular myocytes. Circ Res 1992:70:
743-753.
38. Lerman BB, Belardinelli L. West GA, et al: Adeno-
sine-sensitive ventricular tachycardia: Evidence sug-
gesting cyclic AMP-mediated triggered activity. Circu-
lation 1986:74:270-280.
39. Lerman BB. Wesley RC. DiMarco JP. et al: Antiadren-
ergie effects of adenosine on His-Purkinje automatic-
ity: Evidence for accentuated antagonism. J Clln Invest
1988:82:2127-2133.
40. Lennan BB: Response of nonreentrant catecholamine-
mediated ventricular tachycardia to endogenous adeno-
sine and acetylcholine: Evidence for myocardia! recep-
tor-mediated effects. Circulation 1993:87:382-390.
41. Lerman BB. Stein K. Engelstein ED. et al: Mechanism
of repetitive monomorphic ventricular tachycardia.
Circulation l995;92:421-429.
42. Lerman BB. Belardinelii L: Cardiac electrophysiology
of adenosine: Basic and clinical concepts. Circulation
1991:83:1499-1509.
43. Lee KL. Lauer MR. Young C. et al: Spectrum of elec-
trophysiologic and electropharmacologic characteris-
tics of verapamil-sensitive ventricular tachycardia in
patients without structural heart disease. Am J Cardiol
1996:77:967-973.
44. Gupta RC, Neumann J. Durant P. et al: Ai-adenosine
receptor-mediated inhibition of isoproterenol-stimu-
lated protein phosphorylation in ventricular myocytes:
Evidence against a cAMP-dependent effect. Circ Res
1992:72:65-74.
45. Romano FD, Fenton RA. Dobson JG: The adenosine
Ri agonist, phenylisopropyladenosine. reduces high
affinity isoproterenol binding to the beta-adrenergic re-
ceptor of rat myocardial membranes. Second Messen-
gers Phosphoproteins 1988;12:29-43.
46. Delacey WA. Nath S. Haines DE. et al: Adenosine and
verapamil-sensitive ventricular tachycardia originating
from the left ventricle: Radiofrequency catheter abla-
tion. PACE 1992:15:2240-2244.
47. Kobayashi Y. Kikoshima S, Tanno K, et al: Sustained
left ventricular tachycardia terminated by dipyri-
damole: Cyclic AMP-mediated triggered activity as a
possible mechanism. PACE 1994:17:377-385.
48. DiErancesco D. Mangoni M, Maccafeni G: The pace-
maker current in cardiac cells. In Zipes DP, Jalife J,
eds: Cardiac Electrophysiology: From Cell to Bedside.
WB Saunders Co.. Philadelphia. 1995, pp. 96-103.
49. Belardinelli L. Shryock JC, Song Y. et al: Ionic basis
of the electrophysiological actions of adenosine on car-
diomyocytes. EASEB J 1995:9:359-365.