Premature ventricular complexes in the intramural outflow tract

Ablation of ventricular outflow tract arrhythmias may be limited by the deep intramural location of the arrhythmogenic source. Therefore, a recent study evaluated the acute and long-term outcomes of patients who underwent ablation of premature ventricular complexes (PVCs) in the intramural outflow tract.

Radiofrequency (RF) catheter ablation is an effective and well-established therapy for ventricular arrhythmias (VAs) in patients with and without structural heart disease [2,3]. Most idiopathic VAs arise in the outflow tracts of the right (RVOT) and left ventricles (LVOT) [4–6] and can be successfully treated from the endocardial surface of both ventricles, the aortic sinuses Valsalva, or the distal coronary venous system. Occasionally, however, VAs in the outflow tract may have a deep intramural origin, which presents a particular challenge for ablation because the source may not be readily accessible to standard mapping and ablation catheters. Data suggest that ~10% of idiopathic VAs and up to 20% of LVOT arrhythmias may originate in intramural foci [5,7]. In this case, outcomes are more often suboptimal, with higher rates of failure and arrhythmia recurrence after ablation.

Therefore, in recent years, new strategies have been developed to overcome the limitations of intramural mapping and ablation. Miniaturized multielectrode catheters have been introduced to allow direct mapping of the intramural septum via the septal coronary veins [8]. In addition, unconventional ablation approaches have been developed to achieve deeper lesion formation when standard ablation fails. These include the use of low-ionic irrigants, simultaneous or sequential unipolar ablation from multiple sites, bipolar ablation, needle ablation, and ethanol ablation [7,9–14].

A recently published multicenter study determined the acute and long-term ablation outcomes in a recent series of patients with premature ventricular complexes in the intramural outflow tract and described the ablation strategies required to eliminate these arrhythmias [1].

Structurally normal heart or non-ischemic cardiomyopathy

A total of 92 patients met the inclusion criteria: Age ≥18 years; structurally normal heart or nonischemic cardiomyopathy; catheter ablation of outflow tract PVCs; intramural origin, according to the following criteria:

≥2 of the following criteria: (1) earliest endocardial or epicardial activation <20 ms before QRS; (2) similar activation in different chambers (within 10 ms); (3) no/transient PVC suppression on ablation at the earliest endocardial/epicardial site; or
Earliest ventricular activation recorded in a septal coronary vein.

At the time of ablation, the mean age of patients was 55.3 ± 14.5 years, and 55% (n=51) were male. The majority of patients were New York Heart Association class I (n=60; 65%), with a mean LV ejection fraction (LVEF) of 47.5±13.9% and LV end-diastolic diameter of 54.5±6.8 mm.

The mean PVC load at baseline was 21.5 ± 10.9%. The most common indication for ablation was symptomatic PVCs (n=60; 65%), followed by PVC-induced cardiomyopathy (n=31; 34%) and one case of PVC-induced ventricular fibrillation (n=1; 1%). Seventy-five patients had failed at least one antiarrhythmic drug, and 24 (26%) had failed two or more, of whom 61 (66%) had received prior beta-blocker therapy. 26 patients (28%) had previously undergone unsuccessful ablation. Fifteen patients (16%) had implantable cardiac devices, including three pacemakers, nine dual-chamber ICDs, and three biventricular ICDs (CRT-D). 16 patients had other PVC morphologies (two different PVC morphologies in eight and
Three or more PVC morphologies in eight patients).

MRI scans were performed in 35 patients before the procedure, of which 16 scans showed evidence of delayed gadolinium enhancement of the myocardium. The location of scarring was variable: the interventricular septum was affected in 69% of patients, the inferior wall in 69%, the anterior wall in 25%, and the lateral wall in 31%, with most patients (81%, n=13) having ≥2 regions of scarring on their MRI.

PVC morphologies

Of the 92 PVCs, 63 had a left bundle branch block (LBBB) pattern (68%) and 29 had a right bundle branch block (RBBB) pattern (32%). All exhibited an inferior axis, with monomorphic R waves in the inferior leads. The mean QRS duration was 151 ± 17 ms. Fifty-six patients had a rightward axis (61%) and 35 had a leftward axis (38%) (isoelectric lead I in a PVC). Precordial transitions in LBBB morphology PVCs occurred in V2 in six patients (7%), in V3 in 41 patients (45%), and in V4 in 11 patients (12%). Of the groups of PVCs with earliest site of activation in septal perforators (n=13), 11 had LBBB morphology (83%) with transition at V2 (n=1; 8%), V3 (n=7; 54%), V4 (n=2; 17%), and V5 (n=1; 8%). The average MDI was 0.45 ± 0.8.

Mapping and ablation

In 18 cases, high-density mapping was performed with multielectrode catheters; in the remaining cases, mapping was performed punctually with the ablation catheter. The earliest activation sites were: GCV or AIV 30.4%, LVOT or aortic cusp 28.2%, septal coronary vein 14.1%, RVOT or pulmonary cusp 13.0%, RVOT and LVOT 10.9%, GCV/AIV and LVOT 2.2%, and epicardium in 1.1%. The electrogram at the site of earliest activation (endocardium, epicardium, or coronary venous system) preceded the extrasistolic QRS by 21 ± 10 ms. Direct mapping of the intramural septum with an insulated wire or multielectrode catheter was performed in 29 patients (32%), and in 13 of these cases, the earliest activation was recorded within a septal perforating vein.

Single-site RF ablation was successful in eliminating PVC in only a minority of patients (n=7; 7.6%): from the RVOT (n=2), from the endocardial aspect of the LV ostium below the aortic valve (n=1), from the LCC (n=2), from the RCC (n=1), and from the aorto-mitral continuity (AMC) (n=1). Most patients (n=85; 92%) required the use of specific ablation techniques, including sequential unipolar ablation (n=67; 73%), low ionic flushing with HNS or D5W (n=24; 26%), bipolar ablation (n=14; 15%) (Figure 1 ) [1], and alcohol ablation (n=1; 1%), with 23 patients (25%) requiring ≥2 techniques. In patients undergoing sequential unipolar ablation (n=67), the target sites included the RVOT in 58%, the aortic cusps in 34%, the endocardial LVOT in 67%, the coronary venous system in 45%, and the epicardium in 1%. The most common combinations were LVOT and coronary venous system (n=19; 28.4%), LVOT and RVOT (n=15; 22.4%), and RVOT and aortic cusp (n=12; 17.9%).

In the patient treated with ethanol ablation, the earliest activation was recorded in the proximal aspect of the first septal coronary vein (-50 ms pre-QRS), and initial RF ablation failed in the septal RV and LV endocardium. Distal balloon protection was used to minimize the area of necrosis.

In patients with LBBB morphology (n=63), PVCs were acutely eliminated in 73% of patients, and PVC burden was partially reduced in 18%. This was achieved with specific ablation techniques in 89% of cases, with two alternative techniques required in 30% of cases. The techniques used were low-ion scavenging (25%), sequential unipolar ablation (71%), bipolar ablation (16%), and transcoronary ethanol ablation (2%). RBBB PVCs (n=29) were successfully removed in 79% of cases, and 14% had partial reduction of PVC contamination. Special ablation techniques were required in 90% of cases, with two alternative ablation techniques required in 24% of cases. Ablation techniques included low-ion scavenging (28%), sequential unipolar ablation (76%), and bipolar ablation (10%). The most common combined ablation techniques were low-ionic irrigation combined with sequential unipolar ablation (n=17; 18.5%).

As mentioned previously, the earliest activation was within a septal perforator branch in 13 patients (14%). These PVCs were generally eliminated from endocardial points (n = 10; 83%), although ablation from within the GCV was required in five patients (Fig. 2) [1]. Nine patients were treated with sequential unipolar ablation, with five also using HNS flushing. One patient in this group was treated with ethanol ablation. Acute treatment success was achieved in 12 patients, whereas two patients required repeat ablation. The MDI of PVCs originating from septal perforators was 0.48 ± 0.8, which was not different from those with earliest activation at other sites (0.45 ± 0.8, p=0.4).

Ablation of intramural PVCs poses challenge

At the end of the procedure, 75% of patients had complete suppression of PVCs (n=69) and 16% (n=15) had partial reduction of PVC exposure. The remaining 9% were found to have no effect on PVC exposure. Procedure-related complications included two cases of pericardial effusion requiring pericardiocentesis and a hematoma associated with vascular access.

The mean follow-up time was 15 ± 14 months, and the total PVC burden decreased from 21.5 ± 10.9% at baseline to 5.8 ± 8.4% after ablation (p<0.001). In the 23 patients who had a partial or no response to ablation, the PVC burden before ablation was 20.5 ± 11.9% and decreased to 11.1 ± 10.1% after ablation.

Sixteen patients (17%), including eight patients with acutely successful PVC elimination, required repeat ablation for the same PVC (two procedures in four patients). These were successful in 14 patients, with sequential unipolar ablation in eight cases and bipolar ablation in seven. Three other patients underwent ablation for another PVC (n=2) and for bundle branch VT (n=1). With repeated ablations, complete PVC suppression was achieved in 80% of cases and partial reduction of burden in 12%.

Patients who failed ablation had a wide range of EF (mean 51.9 ± 16.2%). 13 of them were men and 10 were women. The age was 55.8 ± 14 years. The indication for ablation was PVC-related symptoms in 19 cases and PVC-induced cardiomyopathy in four cases. 17 (74%) showed an LBBB pattern (V2 transition in 1, V3 transition in 12, V4 transition in 3, V5 transition in 1) and six (26%) showed an RBBB pattern. In patients with LV dysfunction, LVEF improved from 32 ± 10% before ablation to 42 ± 13% after ablation (p<0.01). This corresponded to an average increase in LVEF of 10 ± 7%.

Take-Home Messages

Acute elimination of intramural outflow tract PVCs is achieved in approximately 3/4 of patients, and repeat ablation is often required.
Ablation from the earliest endocardial or epicardial site achieves PVC elimination in only a minority of patients.
In most cases, PVC suppression requires ablation at multiple endocardial and/or epicardial sites or the use of nonconventional procedures, including low-ionic scavenging solutions (HNS or D5W), bipolar ablation, or ethanol ablation
The most common ECG pattern is an LBBB with inferior axis and V3 or V4 transition.

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