<div>Idiopathic Ventricular Outflow Tract Arrhythmias: Avoid the Use of a
Sledgehammer to Crack a Nut</div><div>Roy M. John, MBBS, PhD</div><div>Alexander C. Perino, MD</div><div>Department of Medicine</div><div>Stanford University School of Medicine</div><div>Palo Alto, CA 94304</div><div>Address for correspondence:</div><div>Roy M. John, MD, PhD</div><div>Stanford School of Medicine</div><div>Center for Academic Medicine</div><div>453 Quarry Road Room 335</div><div>Palo Alto, CA 94304</div><div>Email:
royjohn@stanford.edu</div><div>Word Count: 1436</div><div>Disclosures:</div><div>Roy M John: Lecture honorarium, Abbott Inc.</div><div>Alexander C Perino: Research support from Pfizer inc. and Bristol Myers
Squibb. Consultant for Abbott, Pfizer Inc, and Bristol Myers Squibb.</div><div>Funding: No funding source</div><div>The right (RV) and left ventricular (LV) outflow tracts (OT) are common
sources of premature ventricular contractions (PVCs) and repetitive
ventricular tachycardia (VT) in structurally normal hearts. Most of
these arrhythmias (approximately, 70%) are mapped to early sites just
beneath the pulmonary valves in the RV outflow tract. On the left
ventricular side, sites of successful ablation are more widely
distributed. It spans a course extending from the aortic sinuses,
interleaflet triangles usually between the left and right valve
leaflets, the infra-aortic area on the endocardium to the epicardial
region beneath the coronary venous system overlying the LV summit.
Successful suppression of arrhythmia can be achieved by application of
radiofrequency energy in a variety of locations along this course,
occasionally, well away from the site of recorded earliest activation.
More recently, distal coronary venous systems have been targeted with
alcohol to ablate the LV summit region.<sup>1</sup></div><div>The exact sites of origin of these arrhythmias, particularly left sided
OTs, are therefore controversial. It is likely that the majority
originate in strands of muscles that course from the interleaflet
triangle and adjacent areas of ventricular-arterial (V-A) junction and
insert into the ventricular summit. The myocardial network in the OTs is
complex.<sup>2</sup> Exit sites of triggered activity generated
by these muscle strands are governed by fiber orientation and fibrous
insulation from surrounding myocardium. The premise of insulation is
supported by the fact that during sinus rhythm, discrete potentials with
an isoelectric delay can be recorded from the aortic
sinuses.<sup>3</sup> During PVCs, these potentials precede
ventricular activation by 30-40ms (figure 1) and ablation is usually
successful in the region. However, achieving stability in the LV outflow
interleaflet triangle to record consistent high frequency signals is
difficult. In addition, conventional ablation catheters with a 3.5 mm
tip electrode may not have the resolution to discern these signals.
Often, mapping in the distal great cardiac vein or anterior
interventricular branch of the coronary sinus may record early
electrograms (-30ms or more presystolic). Despite such early activation,
arrhythmia suppression can still be achieved by ablation at the
immediate infra-aortic region by interrupting the course of the muscle
fibers (figure 2). The immediate infra-aortic V-A junction is relatively
thin, measuring 5mm, and allow for transmural
ablation.<sup>4</sup></div><div>Pre-procedural determination of site of origin between the right and
left ventricles is helpful in assessment of risks and benefits of
intervention and procedural planning. In general, most PVCs or VT with
left bundle branch block morphology with precordial transition (the
first precordial lead with R/S ratio &gt;1.0) no earlier than
lead V4 and inferiorly directed axis, have an RVOT origin. Precordial
transition earlier than V3 suggests an LVOT origin. To account for
cardiac rotation, precordial R/S transition during sinus rhythm can be
compared with that of the arrhythmia. In LVOT arrhythmias, precordial
transition tends to occur in the same or earlier precordial lead than in
sinus rhythm, whereas it occurs later in RVOT arrhythmias. Transition in
V3, particularly abrupt transition between V2 and V3, is highly
indicative of an origin from the interleaflet triangle between the left
and right aortic cusps with LV summit exit. <sup>4,5</sup>However, the complex anatomy of the OT and variable exits that are often
distinct from origins, preclude precise localization from ECG alone and
sequential mapping of the RVOT, coronary sinus, aortic root and LVOT is
often necessary for precise definition. Other features such as
variability of coupling interval of the PVCs has been proposed as a
distinguishing feature. Given the more complex course of LV outflow
myofibers, greater variability of coupling interval (&gt; 60
ms variation) is observed in arrhythmias that emerge out of the aortic
sinuses.<sup>6 </sup></div><div>In this issue of the Journal, Waight et al. present a study of analysis
of Holter monitors to assess hourly variability in OT ectopy as the
predictor of site of origin of OT arrhythmias in structurally normal
hearts.<sup>7</sup> The gold standard for site of origin was
successful suppression with ablation. In a derivative cohort of 40
patients, a coefficient of variation of hourly PVCs &gt;0.7
and the presence of any hour with &lt;50 PVCs were found to be
predictive of an RVOT site of origin. In a validation cohort of 29
patients, these parameters prospectively identified the site of origin
in close to 80 to 90% of patients. Any hour with &lt;50 PVCs,
offered the highest probability of the arrhythmia being of RVOT origin
(Youden Index of 78). Arrhythmias of LVOT origin, on the other hand, had
a more even hourly distribution. RVOT PVCs had the highest variability
in the hours between and 0600 and 1200 hours. These are interesting and
novel observations in keeping with the known disproportionate
variability in work-load on the RV compared to the LV with rest and
exercise. Limitations of the study should include ambulatory monitoring
limited to only 24 hours. PVCs demonstrate substantial daily variation.
Recent studies have suggested greater accuracy in detection of PVC
burden with 6-7 days of monitoring.<sup>8</sup> In addition, the
terminology “site of origin” is not strictly applicable as site of
successful ablation can be anywhere along the course of a conducting
muscle fiber and not necessarily the site of origin.</div><div>The authors offer variability in parasympathetic and sympathetic
activation as potential mechanism for RVOT PVC variability. An
additional mechanism worth investigation may be the influence of
mechanical stretch on frequency of triggered automaticity, the proposed
mechanism for outflow arrhythmias in normal hearts. Compared to the LV,
the RV mechanical response to rest and exercise has far greater
variability. Mechanical myocardial stretch during diastole is known to
generate triggered activity and PVCs.<sup>9</sup></div><div>Given the growing importance of PVC and repetitive VT on ventricular
function, the current paper adds significantly to the gross
differentiation between the sites of origin. What needs better
definition is the exact anatomical relationship between the origins and
exits points for these arrhythmias such that indiscriminate and large
volume ablation of ventricular muscle tissue can be avoided. We
shouldn’t have to use a sledgehammer to crack a nut.</div>