Multifocal Ventricular Arrhythmias Originating From the His-Purkinje System

Incidence, Characteristics, and Outcome of Catheter Ablation

Patient characteristics

The study population consisted of 30 consecutive patients (15 men; age 55 ± 16 years) who underwent RFCA of symptomatic focal HPS VAs between April 2010 and December 2016. The baseline characteristics, including age, sex, left ventricular function, nature of the clinical arrhythmias, and 12-lead electrocardiograms during the VAs, were recorded. The institutional review board approved the study protocol, and all patients provided written informed consent for the procedure. All antiarrhythmic drugs, except amiodarone, were discontinued for at least 5 half-lives before the study.

Electrophysiological study

For mapping and pacing, multipolar catheters were positioned in the coronary sinus and His bundle region via the right femoral vein. A 3.5-mm tip irrigated ablation catheter (Navistar ThermoCool, Biosense Webster, Diamond Bar, California) was introduced into the left or right ventricle through the right femoral artery or vein, respectively. During the procedures in the left ventricle, intravenous heparin was administered to maintain an activated clotting time of >300 s. When few premature ventricular contractions (PVCs) were observed at baseline, induction of VAs was attempted by burst ventricular pacing, with the addition of isoproterenol infusion at 2 to 4 μg/min. A mechanism of sustained ventricular tachycardia was diagnosed as focal by the absence of any entrainment phenomenon during overdrive pacing (Figure 1).

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Figure 1

Intracardiac Tracings Demonstrating the Absence of an Entrainment Phenomenon in Response to Overdrive Pacing During Sustained Ventricular Tachycardia

CS = coronary sinus; HB = His bundle; Xd(p) = the distal (proximal) electrode pair of the relevant catheter.

Mapping and RFCA

Electroanatomical mapping was performed using a 3-dimensional mapping system (CARTO, Biosense Webster). When VAs exhibited multiple different QRS morphologies, activation mapping was performed during the VAs with the most dominant QRS morphology. When Purkinje potentials preceding the QRS onset were recorded during both the VAs and sinus rhythm, those VAs were considered to originate from the HPS (Figure 2). The 3 fascicles in the left ventricle were delineated with an anatomic consideration on the 3-dimensional map by mapping pursuing the Purkinje potentials (Figure 3). Activation mapping along the fascicles was performed with a combination of 3-dimensional mapping and conventional mapping that compared the activations recorded from the distal and proximal electrode pairs of the mapping catheter. With this mapping technique, even a few mapping points could reveal an activation pattern of the Purkinje potentials and could identify a site of an HPS VA origin. When a QRS complex did not follow the Purkinje potentials, it was considered that a conduction block between the VA origin and ventricular myocardium (P-Vpvc block) occurred. When 2 separated Purkinje potentials with a short interval were followed by a QRS complex, those Purkinje potentials were defined as split Purkinje potentials. Pace mapping was performed using the distal bipolar electrodes at a pacing cycle length of 500 ms and at the minimum stimulus amplitude required for consistent capture, up to an output of ≤20 mA and pulsewidth of 2.0 ms. The pace map score was determined as the number of leads with identical heights of the R wave/depth of the S wave (R/S) ratio match (12 represented a perfect R/S ratio match in all 12 leads) and the number of leads with fine notching matches in the 12-lead electrocardiogram (perfect pace mapping was equal to 24 points). A VA-matched pace map was defined as a pace map with a score of ≥21.

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Figure 2

Case 1 With 2 PVCs Originating From the LAF and the LPF

(A and B) Cardiac tracings (left and middle panels) and fluoroscopic images (right panels) exhibiting the breakout sites or successful ablation sites of premature ventricular contractions (PVC1 and PVC2, respectively). The arrows indicate the activation sequence of the Purkinje potentials (PPs) recorded from the distal and proximal bipoles of the ablation catheter during the sinus beat and the PVC. The open arrows indicate the retrograde HB electrogram. ABL = ablation catheter; LAF = left anterior fascicle; LAO = left anterior oblique; LPF = left posterior fascicle; PP-sQRS (vQRS) = the interval between the PP and QRS onset during sinus rhythm (PVCs); RAO = right anterior oblique; other abbreviation as in Figure 1.

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Figure 3

Case 4 With 3 PVCs Originating From the LSF, LPF, and LAF

(A) Twelve-lead electrocardiograms exhibiting sinus beats (SBs), junctional beats (JBs), and multifocal PVCs originating from the left septal fascicle (LSF). (B) Activation map of PVC1 (left panel) and cardiac tracings exhibiting the earliest activation during PVC1 (right panel). (C) Cardiac tracings exhibiting the earliest and later activations on the same fascicle during PVC1 (left and right panels, respectively). (D) Cardiac tracings exhibiting the local activations at the breakout sites during PVC1 to PVC3 (left, middle, and right panels, respectively). (E) Cardiac tracings exhibiting the earliest activation during PVC4 (left panel) and that during PVC5 after successful ablation of PVC4 (right panel). In the activation map, the yellow and red tags indicate the sites recording PPs and those of ablation, respectively. The numbers of the ablation sites (from 1 to 5) indicate the order of RF applications. The open arrowheads indicate PPs recorded after the QRS onset during SBs or JBs. Radiofrequency catheter ablation (RFCA) at the distal and mid-LSF (RF1 and RF2 sites, respectively) failed to eliminate PVC1, but resulted in a distinguishable change in QRS morphologies of PVC1 and PVC2 (B and C). Pre-systolic PPs were recorded at the LAF and LPF during PVC2 and PVC3, respectively. Further mapping during PVC1 revealed the earliest activation at the proximal LSF (RF3 site), where a PP preceded the QRS onset by 25 ms during PVC1 (arrowhead in C). At this site, a PP also preceded the QRS onset by 42 ms during PVC2 and by 56 ms during PVC3 (arrowheads in C). RFCA at this site successfully eliminated all 3 PVCs at the same time. After this ablation, PVC4 and PVC5 occurred (E). PVC4 was successfully ablated at the proximal LAF (RF4 site), and resulted in the development of LBBB (E). PVC5 was successfully ablated at the distal LPF (RF5 site), (E). LAT = local activation time; LV = left ventricular; other abbreviations as in Figures 1 and 2.

Irrigated radiofrequency energy was delivered at sites that exhibited the earliest bipolar activation and/or a local unipolar QS pattern preceding the QRS onset during the VAs. Irrigated radiofrequency current was delivered in the power-control mode, starting at 30 W, with an irrigation flow rate of 30 ml/min. The radiofrequency power was titrated up to 50 W, with the goal of being able to achieve a decrease in the impedance of 8 to 10 ohms, and with care taken to limit the temperature to <40°C. When an acceleration or reduction in the incidence of VAs was observed during the first 10 s of the application, the radiofrequency delivery was continued for 60 to 120 s. Otherwise, the radiofrequency delivery was terminated, and the catheter was repositioned. When VAs with different QRS morphologies remained after the successful ablation of the first VAs, mapping and RFCA were performed with the same protocol. The endpoint of the RFCA was the elimination and noninducibility of VAs during an isoproterenol infusion of 2 to 4 μg/min and burst ventricular pacing (to a cycle length of ≥240 ms).

Definition of multiple HPS VA origins and a single HPS VA origin with preferential conduction to multiple breakout sites

When the Purkinje potentials preceding the QRS onset during VAs or VA-matched pace maps were recorded at a fascicle, it was considered that a breakout site should be located at that fascicle. When the activation of a Purkinje potential recorded during VAs was earlier at a distal site than a proximal site in the same fascicle, it was considered that the HPS VA origin should be located at that fascicle. When earlier Purkinje potentials during VAs were recorded or successful RFCA of VAs was achieved at a fascicle distinct from that with a breakout or proximal LBB, it was suggested that there should be preferential conduction from the origin of the VA to the breakout site within the HPS. Based on these definitions, when multiple HPS VA origins were identified in a patient, the patient was determined to have multifocal HPS VAs, which were differentiated from VAs with preferential conduction from a single origin to multiple breakout sites. Those definitions could rule out an induction of an exit block of the first HPS VA origin by mapping and RFCA, with a shift of the breakout site to a distant location.

In this study, the intrinsic QRS morphologies recorded at baseline were mapped first. However, different QRS morphologies from those at baseline could occur during mapping and after RFCA for 2 possible reasons. First, suppression or disappearance of the major VAs by HPS impairment or elimination of the origins by RFCA could allow VAs originating from a different origin to emerge. Second, HPS impairment could change the conduction pattern within the HPS, resulting in different QRS morphologies. In this study, QRS morphologies newly developed after the instrumentation in the ventricles or RFCA were also studied when it was assured that those QRS morphologies occurred with the first mechanism.

Unifocal and multifocal HPS VAs were classified into subgroups according to the presence of preferential conduction within the HPS. Unifocal HPS VAs without and with preferential conduction were grouped as UF-1 and UF-2, respectively. Multifocal HPS VAs without and with preferential conduction to multiple different fascicles or a single fascicle were grouped as MF-1, MF-2, or MF-3, respectively.

Electrocardiographic analysis

Simultaneous 12-lead electrocardiograms during VAs and pace mapping were recorded digitally at sweep speeds of 200 mm/s in all patients for an offline analysis. The QRS morphologies, including a bundle branch block pattern, the axis, and the configuration in leads I and V₆, were examined. The QRS duration and coupling interval of VAs were measured with electronic calipers by 2 experienced investigators blinded to the site of the origin. For analysis of the coupling intervals, the first 10 consecutive beats of the clinical VAs that were recorded during the procedure were selected.

Follow-up

Follow-up after the procedure included clinic visits with 12-lead electrocardiography and 24-hour Holter recording, and telephone calls to all patients and their referring physicians. All patients who reported symptoms underwent 24-hour Holter recording or event monitoring to document the cause of the symptoms. Successful ablation was defined as no recurrence of any VAs during >6 months of follow-up.

Statistical analysis

Continuous variables were expressed as mean ± SD. Comparisons of the continuous variables between the 2 groups were analyzed with the 2-tailed paired t-test or Mann-Whitney U test. Comparisons of the continuous variables among the 3 groups were analyzed with 1-way analysis of variance. When appropriate, a further post hoc pairwise comparison was performed by Tukey’s test. The categorical variables, which were expressed as numbers and percentages in the different groups, were compared with a chi-square test and Yates correction, if necessary. Freedom from recurrent HPS VAs or VF was determined by Kaplan-Meier analyses with a log-rank test. Statistical significance was selected as p < 0.05.