Jorge Romero, MD, Luigi Di Biase, MD, PhD, FACC, FHRS, Pasquale Santangeli, MD, Alessandro Paoletti Perini, MD, Francesco Santoro, MD, Rong Bai, MD, J. David Burkhardt, MD, Andrea Natale, MD, FHRS, FESC, FACC
CASE PRESENTATION
A 48-year-old man without any significant past medical history was brought to the emergency department with severe dyspnea and dizziness. He reported similar symptoms for the past 4 months. Electrocardiogram (ECG) revealed monomorphic ventricular tachycardia (VT) at 180 bpm with a left bundle branch block (LBBB) morphology, inferior axis, early transition in lead V2 and R/S wave amplitud >0.3 and R-wave duration index (R/QRS) > 0.5. Amiodarone was administered with restoration of normal sinus rhythm. Patient underwent electrophysiology study (EPS) with ECG showing only ventricular bigeminy right before the procedure (Figure 19-1A) and sporadic premature ventricular contractions (PVCs) during EPS. Mapping of the right ventricular outflow tract (RVOT) did not reveal early local activation or similar pace maps. By retrograde approach, the aortic root and coronary cusps were mapped. Earliest depolarization was noted at the commissure between the right and the left aortic cusp (Figure 19-1B), and pace-mapping produced a similar QRS morphology (Figure 19-1C). After aortic angiogram was performed to visualize the coronary arteries, multiple radiofrequency energy applications were given at the commissure with suppression of spontaneous PVCs. Complete suppression was obtained at the end of the procedure. Patient has been asymptomatic for 6 years on no medical therapy without any recurrence of ventricular ectopy by ambulatory event monitoring.
FIGURE 19-1A A 12-lead electrocardiogram (25 mm/sec) depicting ventricular bigeminy with an inferior axis and LBBB morphology premature ventricular contractions (PVCs). Notice a QS morphology in lead V1 with notching on the downward deflection with precordial early transition in lead V3 that suggests PVCs originating in the commissure between the left and right aortic cusps.
FIGURE 19-1B Activation mapping of the same patient using a bipolar catheter. Notice intracardiac electrograms revealing the earliest activation (ie, 37 msec) preceding the QRS complex (PVC) at the commissure between the right and the left aortic cusp.
FIGURE 19-1C Pace-mapping demonstrating identical PVC morphology at the commissure between the right and the left aortic cusp.
EPIDEMIOLOGY
Ventricular tachycardia (VT) originating from the left ventricular outflow track (LVOT) particularly from the aortic cusp is part of the large family of the so-called “idiopathic ventricular arrhythmias” (IVT), which occur mostly in structurally normal hearts. Aortic cusp VT is rare, given that RVOT VT accounts for almost 80% to 85% of IVTs, whereas it accounts for only 30% of LVOT VTs.1 It has no gender preference; it might occur at any age and mostly on exertion given its catecholamine-induced nature, but it can also occur at rest. Although, thought to have a benign course, patients with frequent premature ventricular contractions (PVCs) or episodes of VT might develop tachycardia-induced cardiomyopathy and sudden cardiac death. The first case series reporting, patients with VT arising from the aortic sinus of Valsalva was published in 2001. This included 12 patients with LBBB and inferior axis VT with characteristic ECG findings with previously failed ablation, all of whom were successfully ablated from the aortic root.2
ANATOMY OF THE AORTIC ROOT
The aortic valve is the “heart” of the heart. Almost every single structure is directly related to this valve including all four chambers and the rest of the cardiac valves. Its area is approximately 3 to 4 cm2. Generally, it has three leaflets attached to the aortic annulus but in 1% to 2% of the population the aortic valve might be unicuspid, bicuspid, or quadricuspid. Right above these semilunar (crescent-shape) leaflets are the Valsalva sinuses (VS), which are small dilatation of the ascending aorta. Two of them (ie, left and right) give rise to the left main coronary artery (LMCA) and right coronary artery (RCA) from their superior aspects. They are mainly made up of connective tissue with some muscular bundles from the ventricle. The coronary ostia diameters are 2 to 5 mm for RCA and 4 to 7 mm for LMCA.
The aortic root is an anterior cardiac structure, but it is anatomically posterior and somewhat rightward related to the RVOT. The left aortic sinus is in close contact with left atrium, pulmonary artery, and aortomitral continuity. The right sinus is posterior to the RVOT and close proximity to the tricuspid valve, and the noncoronary sinus is anterior to the lower portion of the interatrial septum, which is of critical importance when performing transseptal punctures (Figure 19-2).
FIGURE 19-2 Aortic root with a transverse section at the level of the sinotubular junction depicting each of the three aortic sinuses of Valsalva (SV), the left coronary cusp (LCC), the right coronary cusp (RCC), and the noncoronary cusp (NCC). The left main coronary artery (LMCA) and the right coronary artery (RCA) are also noted.
ETIOLOGY AND PHYSIOPATHOLOGY
The origin of this type of VT is mostly located at the bottom of any of the sinuses of Valsalva, most commonly from the left followed by the right and rarely from the noncoronary cusps (NCC). Pathology reports have shown that this arrhythmia arises from sleeves of myocardium in the cusps, which are most likely extensions of ventricular muscle into the base of the aortic cusps.3 The lack of muscular tissue in the NCC renders it without a substrate for arrhythmia formation. Another hypothesis is that in patients with idiopathic dilated cardiomyopathy the basal left ventricular scar may extend into to the aortic sinus of Valsalva, providing the substrate for aortic cusp VT.4
Accumulating evidence has suggested that this arrhythmia is related to cAMP-mediated triggered activity with an increase of intracellular calcium, which causes early or delayed after-depolarizations. Consequently, similarly to RVOT VT and other forms of LVOT VT, aortic cusp VT is sensitive to substances (ie, adenosine, acetylcholine, β-blockers) that directly interact with adenylyl cyclase by inhibiting the production of cAMP through G proteins.5Likewise, verapamil might also terminate this arrhythmia by direct blocking of calcium receptors and in turn diminishing the available calcium to the sarcoplasmic reticulum.
DIAGNOSIS
Clinical Presentation
• Broad spectrum from monomorphic premature ventricular contractions (PVCs) to repetitive nonsustained VT (NSVT) or paroxysmal sustained monomorphic VT (SMVT).
• Programmed stimulation during EPS can induce and terminate it, especially in patients presenting with SMVT.
Diagnostic Tests
• ECG at rest, signal average electrocardiogram (SAECG), and microvolt T-wave alternans (TWA) are usually unremarkable.
• Exercise testing might induce VT in the vast majority of patients who present with SMVT but only a small percentage of patients with NSVT or PVCs.6
• Based on its mechanism of action (ie, cAMP-triggered activity), this arrhythmia can be initiated and terminated by programmed stimulation with either atrial or ventricular rapid pacing during EPS, sometimes requiring isoproterenol infusion.
• Entrainment is not feasible due to lack of a reentry loop.
• Adenosine, verapamil, and vasovagal maneuvers usually terminate this arrhythmia.
• For those patients presenting with frequent PVCs, 24-hour Holter monitoring should be considered to assess PVC burden.
Electrocardiography
The 12-lead ECG during episodes of VT is of paramount importance since it might narrow the differential diagnosis and guide the approach of VT ablation. Specific ECG patterns have been recognized in order to localize the exact place where the studied VT is originating. The PVC/VT usually has a LBBB morphology and inferior axis (positive deflection in inferior leads). The main and most helpful criterion to differentiate among the large variety of VT coming from the “ventricular outlet track” is the QRS transition zone in the precordial leads, in which QRS complex becomes positive. The basic approach is as follows:
• The more anterior the VT source is, the later the transition in the precordial leads is going to be (ie, leads V4-V5).
• Conversely, the more posterior the structure, the earlier the transition zone will be (ie, V1-V2).
• Consequently, RVOT-VT and LVOT-VT usually have transition zones in V4-V5 and V1-V2, respectively. There are more specific criteria in order to further localize each arrhythmia in each outlet track.
RVOT
• Transition zone V3 or later + QRS duration <140 msec favors the septum.
• Transition zone V4 or later + QRS >140 msec favors the free wall.
• To discern from left to right within the RVOT, QS complex amplitude in aVR and aVL is usually analyzed.
If aVR > aVL favors a right location.
If aVR < aVL favors a left location.
• To discern a superior origin within the RVOT:
a high R-wave amplitude in V1 indicates a superior origin.
a low R-wave amplitude in V1 indicates an inferior location.7
Pulmonary Artery
• Transition zone in V3-V4
• High amplitude R waves in inferior leads since it is superior to RVOT
• QS in aVL > aVR (leftward of RVOT)
• qR in lead I8
Tricuspid Valve
The vast majority of VTs in tricuspid annulus originate in the proximity to His-bundle (para-Hisian or anteroseptal).
• Transition zone V2-V3.
• Low amplitude R waves in inferior leads since it is inferior to RVOT.
• a RR’ or RsR’ pattern in aVL.
• No R wave in V1.9
Aortic Cusp
• Transition zone in V2-V3 with rS morphology in V1-V2.
• R/S wave amplitude index >0.3 and R-wave duration index (R/QRS) >0.5 examined in V1-V2 favors VT originating from sinuses of Valsalva.
• An earlier R/S transition zone (V2) and higher R-wave amplitude and duration for VTs from the left coronary cusp (LCC) when compared to the VTs coming from the right coronary cusp (RCC).10
In LCC VT, inferior leads have a pointed and tall positive QRS, notched QRS in V6, and rS pattern in lead I.
• VTs from the commissure between the left and right aortic cusps generally have a qrS pattern in leads V1-V3 and/or have a QS morphology in lead V1 with notching on the downward deflection with precordial transition at lead V3.11,12
Epicardial Sites (Great Cardiac and Anterior Interventricular Veins)
• Early transition zone V2-V3 (generally RBBB)
• aVL/aVR wave amplitude index >1.4
• S wave in V1 >1.2 mV
• A useful ECG parameter to differentiate this origin from aortic cusp VTs is the intrinsicoid deflection (R-wave peak time/QRS) >55% indicating a slowed initial precordial QRS activation.13
Aortic Valve-Mitral Valve Continuity (AV-MV)
• Transition zone V1-V2 almost simulating a RBBB morphology.
• Broad monophasic R-waves throughout the precordial leads.
• S wave in V6 particularly if the source is the anterolateral, lateral, or posterior portion of the mitral annulus14 (Figures 19-3A and 19-3B).
FIGURE 19-3A Long axis view of the base of the heart seen from above. Note the close relationship between the aortic valve and the RVOT, pulmonary, and mitral valves. The roman numerals indicate possible sites of origin of VT and their relationship with the aortic sinus of Valsalva: (I) Right ventricular outflow track (RVOT) anterior wall; (II) RVOT posterior wall; (III) pulmonary valve; (IV) tricuspid valve; (V) right coronary cusp (RCC); (VI) commissure between the left and right aortic cusps; (VII) left coronary cusp (LCC); (VIII) interventricular vein (Epicardial site); (IX) Aortic valve-mitral valve continuity (AV-MV).
FIGURE 19-3B Short axis view of the heart seen from left to right. (I) Right ventricular outflow track (RVOT) anterior wall; (II) RVOT posterior wall; (III) right coronary cusp (RCC); (IV) left coronary cusp (LCC); (V) Aortic valve-mitral valve continuity (AV-MV) and mitral annulus.
DIFFERENTIAL DIAGNOSIS
As mentioned in the diagnosis section, there are a myriad of distinct VTs that can mimic aortic cusp VT. Besides different types of IVT originating from RVOT, pericardium and mitral, or tricuspid annuli, it is worth mentioning that arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) sometimes presents with a similar ECG pattern (ie, LBBB and inferior axis). Nevertheless, the ECG in this inherited cardiomyopathy is often accompanied by T-wave inversion in the right precordial leads and rarely with the pathognomonic epsilon wave. Magnetic resonance with delayed enhancement and endomyocardial biopsy might help in the diagnosis by identification of myocardial fibro-fatty infiltration.
MANAGEMENT
Pharmacological Therapy
Acute Management
In the acute setting, aortic cusp VT responds very well to escalating doses of adenosine starting with 6 mg and up to 18 mg every 2 minutes. Verapamil IV and lidocaine drip might also be reasonable options.
Chronic Management
Asymptomatic or mildly symptomatic patients are mostly treated with β-blockers with minimal suppression of ventricular ectopy. Moreover, nondihydropyridine calcium channel blockers (CCB) such as diltiazem and verapamil can be added to refractory cases as an adjuvant therapy. Antiarrhythmic medications (eg, amiodarone, sotalol) have also been implemented in the management of these patients with satisfactory results. However, several permanent side effects of these medications, particularly of amiodarone, outweigh their potential therapeutic benefits.
Invasive Therapy
Catheter ablation (CA) is usually reserved for the management of symptomatic patients with frequent episodes of NSVT/SMVT, for patients with significant PVC burden quantified by ambulatory monitoring, or for patients with history of presyncope or syncope. If quantification of burden of PVCs is greater than 20% to 25% even in asymptomatic patients, CA is strongly recommended in order to prevent or correct LV dysfunction.15
CA is highly effective with success rates ranging from 90% to 95%. CA of aortic cusp VT may be challenging due to the complex anatomy. Several structures within the LVOT and RVOT are only separated by millimeters, and completely different approaches might be needed in order to map and ablate any specific type of IVT. Nevertheless, once mapping is performed and the exact localization of the VT source is achieved, CA is relatively simpler than in patients with VT due to structural heart disease since the area to be ablated is significantly smaller and more superficial.
Frequently, induction of the ventricular arrhythmia being studied during EPS may be cumbersome and infusion of isoproterenol alone or in combination with phenylephrine may be necessary. Subsequently, heavy sedation or general anesthesia should be avoided if feasible.
Activation mapping is thought to be the most accurate way to identify the earliest site of activation during spontaneous or induced PVC/VT and subsequently the best modality to obtain high success (see Figure 19-1B). The mapping is completed via a retrograde approach through the femoral arteries, usually after having mapped the RVOT and coronary sinus meticulously.
Although pace-mapping has been widely used, it might yield inadequate sites for ablation because similar VT maps can be obtained with a radius of 10 mm from the VT source (see Figure 19-1C). Yamada et al demonstrated that VT originating from the aortic cusps often (25%) shows preferential conduction to the RVOT with both closer match of QRS morphology from the RVOT than pacing from within the aortic cusp and significantly longer stimulus-QRS interval from aortic cusp than from RVOT, which renders pace-mapping less reliable.16 Nevertheless, Azegami et al compared the special resolution and specificity of both pacing and activation mapping using three-dimensional mapping technologies. They reported that the mean area of myocardium activated within the first 10 msec was 3.0 ± 1.6 cm2, concluding that neither of these two techniques yields perfect targets for ablation since the special resolution of each technique is only modest. Hence, the integration of both of them might be the best approach and it was the approach used for the case presented in this review.
Identification of the right coronary artery (RCA) and left main coronary artery (LMCA) ostia is routinely performed by most electrophysiology laboratories. This might be achieved by different imaging modalities, including aortic root angiography and intracardiac echocardiography (ICE) (Figure 19-4). LMCA or RCA can be cannulated for guidance and protection during CA. The mean distance between the coronary ostia and ablation site is in general 11 millimeters.
FIGURE 19-4 Ablation of the left coronary cusp guided by intracardiac echocardiography (ICE). Direct and constant visualization of the left main coronary artery (LMCA) significantly reduces the risk of severe complication while performing this procedure.
CA frequently uses radiofrequency energy, which is maintained for 100 to 120 seconds to reach a temperature of 131°F (55°C), generally low power (15-30 watts) is enough at this area. CA should preferably be performed with simultaneous fluoroscopy to assess catheter position at all times. Cryoablation has been proposed and tested for aortic cusp ablation to prevent potential complication particularly damage of the coronary arteries with less favorable success rates.
COMPLICATIONS
Coronary artery thombosis, stenosis, rupture, or dissection may occur in a minority of cases. Likewise, either aortic rupture with cardiac effusion/tamponade or fistulae to left or right atria and aortic dissection have been reported. Aortic insufficiency and aortic leaflet perforation can also occur.
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