Catheter ablation in patients with pleomorphic, idiopathic, premature ventricular complexes

Accepted Manuscript Catheter Ablation in Patients with Pleomorphic, Idiopathic, Premature Ventricular Complexes Seth H. Sheldon, MD, Rakesh Latchamsetty, MD, FHRS, Fred Morady, MD, Frank Bogun, MD PII:

S1547-5271(17)30777-4

DOI:

10.1016/j.hrthm.2017.06.028

Reference:

HRTHM 7215

To appear in:

Heart Rhythm

Received Date: 28 February 2017

Please cite this article as: Sheldon SH, Latchamsetty R, Morady F, Bogun F, Catheter Ablation in Patients with Pleomorphic, Idiopathic, Premature Ventricular Complexes, Heart Rhythm (2017), doi: 10.1016/j.hrthm.2017.06.028. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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ACCEPTED MANUSCRIPT Catheter Ablation in Patients with Pleomorphic, Idiopathic, Premature Ventricular Complexes

Seth H. Sheldon1, MD, Rakesh Latchamsetty2, MD, FHRS, Fred Morady2, MD, Frank

Division of Cardiovascular Diseases, University of Kansas Medical Center, Kansas City, KS Division of Cardiovascular Diseases, University of Michigan, Ann Arbor, MI

Sources of Financial Support: None Conflicts of Interest: Seth Sheldon: None Rakesh Latchamsetty: None

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Fred Morady: None

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Bogun2, MD

Frank Bogun: None Word count: 3263

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Abstract word count: 249

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Short title: Ablation of Pleomorphic Premature Ventricular Complexes Corresponding Author:

Frank Bogun Division of Cardiovascular Diseases University of Michigan 1500 E. Medical Center Dr. Ann Arbor, MI 48109-5853 Phone: 734-232-0112 E-mail: [email protected]

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Background: Premature ventricular complexes (PVCs) often originate from multiple locations. Objective: The goals of this study were to assess characteristics of patients with pleomorphic, idiopathic PVCs and to determine the impact of pleomorphic PVCs on outcomes. Methods: Records were collected from 153 consecutive patients referred for

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ablation of PVCs. Patients with structural heart disease (n=34) or inadequate ambulatory ECG data (n=19) were excluded. Results: Among 100 consecutive patients (age 52 ± 15 years, 53% men, 31% pleomorphic vs. 69% monomorphic) referred for ablation of idiopathic

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PVCs, the success rate was lower in patients with pleomorphic PVCs vs. monomorphic PVCs (71 vs. 90%, p=0.017, overall 84%). The presence of pleomorphic PVCs was independently

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associated with unsuccessful ablation. A cut-off of ≥156 non-predominant PVCs over 24 hours best differentiated successful from unsuccessful ablation procedures (AUC: 0.64, sensitivity 56%, specificity 74%). Patients with pleomorphic vs. monomorphic PVCs more often have an epicardial origin (29 vs. 9%, p=0.008). Repeat ablation procedures were

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required in 20 patients (20%, 6 had pleomorphic PVCs). Sixteen / 20 (80%) patients had recurrence of the former predominant PVC, three / 20 patients (15%) had an increase of a non-predominant PVC and one patient (5%) had a newly emerging PVC focus. Conclusion:

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The presence of pleomorphic PVCs impacts ablation outcomes. Successful elimination of the

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predominant PVC often results in successful ablation, even if not all PVCs are targeted. While pleomorphic PVCs infrequently require repeat ablation procedures, most recurrences are due to reemergence of the originally targeted predominant PVC morphology.

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ACCEPTED MANUSCRIPT Keywords: Ventricular Premature Complexes

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Catheter Ablation

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Electrocardiography, Ambulatory

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Idiopathic

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Pleomorphic

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Monomorphic

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ECG: Electrocardiographic

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LGE: Late gadolinium enhancement

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LVEF: Left ventricular ejection fraction

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PVC: Premature ventricular complexes

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ROC: Receiver-operator curve

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ACCEPTED MANUSCRIPT Introduction:

Premature ventricular complexes (PVCs) in a given patient can originate from one or multiple foci, even in the absence of structural heart disease. The success rate of ablation is lower in patients with pleomorphic compared with monomorphic PVCs.1,2 The clinical

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characteristics, determinants of outcome, and dynamics of the PVC burden of non-dominant PVCs are unknown in patients with pleomorphic PVCs. We sought to compare clinical characteristics and outcomes of patients with pleomorphic versus monomorphic idiopathic

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PVCs.

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Methods: Patients Characteristics

From a patient population of 153 consecutive patients referred for PVC ablation at a single tertiary center between September 2011 and April 2016, a total of 100 patients with

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frequent idiopathic PVCs were the subjects of this study (mean age 52 ± 15 years, 53% men). The 53 excluded patients had either: structural heart disease (n=34) or absence of adequate ambulatory electrocardiographic (ECG) data (n=19). All patients underwent an assessment

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for the presence of structural heart disease with echocardiography, stress testing, and/or

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cardiac magnetic resonance imaging. Patients with myocarditis, infiltrative heart disease, prior myocardial infarction, or definitive late gadolinium enhancement (LGE) on cardiac MRI were excluded. Patients with coronary artery disease in the absence of LGE on cardiac MRI were included in the study. In patients with an ejection fraction <50% in the absence of scarring on cardiac MRI, the decreased ejection fraction was attributed to PVC-induced cardiomyopathy. All patients underwent pre-procedural and post-procedural ambulatory ECG monitoring. The patients’ clinical characteristics are displayed in Table 1. Thirty patients

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(30%) underwent prior ablations at an outside medical center. The Institutional Review Board approved the study protocol.

Ambulatory ECG monitoring

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Twenty-four hour 12–lead ambulatory ECG monitoring (Spacelabs Healthcare, Impresario, Hawthorne, CA) was performed before and after the ablation procedure. Data collected from the ambulatory ECG monitor included PVC burden, number of distinct PVC

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morphologies, and PVC coupling interval. Analysis was limited to single PVCs. Each PVC morphology and count from the ambulatory ECG monitoring was manually reviewed to

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determine the number of distinct PVC morphologies. A distinct PVC morphology was defined as a PVC morphology that differed from other PVCs in >2 /12 ECG leads. We constructed a receiver-operator characteristics (ROC) curve where the PVC burden of the non-predominant PVCs was plotted against the ablation outcome to

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quantitatively define a patient with pleomorphic PVCs. A predominant PVC was defined as a PVC morphology with a prevalence of >80% of all PVC morphologies1. The PVC coupling intervals were measured from the onset of the intrinsic rhythm QRS to the onset of the PVC

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and averaged after measurement of up to five intervals. Ambulatory ECG monitoring was performed prior and approximately 3-4 months post-ablation. Successful ablation was

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defined as a ≥80% reduction of the initial overall PVC burden at 3-4 months post-ablation3.

Mapping and Ablation

After informed consent was obtained, several multipolar catheters were placed in the right atrium, the His bundle position, and the right ventricle. Activation mapping was performed for frequent PVCs and pace-mapping for infrequent PVCs. For right-sided procedures, 3000 units of heparin were initially administered as a bolus followed by 1000

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units every hour. For left-sided procedures, a 5000-unit bolus was administered after arterial access was obtained and the heparin dosage was then titrated to maintain an activated clotting time of ≥250 seconds. A 3.5-mm open-irrigated-tip catheter (Biosense Webster Inc, Diamond Bar, CA) was

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used for mapping and ablation. The primary goal of the procedure was ablation of the predominant PVC as seen on ambulatory ECG monitoring. In the few circumstances where a non-predominant PVC was more frequent during mapping, it was first ablated followed by

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mapping and ablation of the predominant PVC. A focus was classified as intramural when mapping on adjacent walls showed early activation yet the pace mapping did not match with

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the targeted PVC morphology (match <10/12 leads).4 Cold saline injection confirmed the intramural origin of the PVCs, as suppression of frequent PVCs when chilled saline was infused into the great cardiac vein indicated an intramural focus in the basal left ventricle.5 A focus was considered epicardial if early timing was present and pace-mapping matched the

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targeted PVC morphology from the epicardium either via a subxiphoid approach or the coronary venous system in ≥10/12 leads.

Radiofrequency energy was delivered in the right ventricle, pulmonary artery, aortic

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cusps, coronary venous system with an initial power of 20 Watts that was increased up to 30

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Watts to achieve an impedance drop of 10 Ω. For arrhythmias originating from the left ventricular endocardium, or epicardium the power was increased from 30 to 50 Watts to achieve an impedance drop of 10 Ω. Statistical Analysis

Descriptive statistics are presented as mean and standard deviation for normally distributed continuous variables, median and interquartile range for abnormally distributed continuous variables, or number and percentage for categorical variables. Parameters of interest were compared between groups using the Pearson chi-square test for categorical

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variables and two-sample student t-test for continuous variables. Logistic regression analysis was used to determine the independent predictors of successful ablation. The final multivariate model was selected in a stepwise manner (removing one non-significant parameter at a time) using characteristics with univariate P values < .20 as candidate

values <0.05 were considered to be statistically significant.

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Results:

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variables. JMP Pro version 11.2.1 (SAS; Cary, NC) was used for all statistical testing and p-

Patient Characteristics and Follow-up

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A cardiac MRI was available to exclude LGE in 91 of 100 patients. Clinical follow-up duration was a median of 17 months (IQ range 5.8-36.8 months). Ambulatory ECG followup duration was a median of 5.6 months (IQ range 2.9-33.3 months). The PVC ablation was successful in 84/100 patients (84%). Among the 17 patients with left ventricular ejection

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fraction (LVEF) <50% pre-procedure, the LVEF improved to >50% in 12/17 patients (71%).

Outcomes: Monomorphic versus pleomorphic PVC source

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With a non-predominant PVC burden ≥156 over 24 hours, a successful ablation

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procedure was best separated from a failed procedure (Appendix 1, area under the curve: 0.64, sensitivity 56%, specificity 74%). The median non-predominant PVC burden was 0 over 24 hours (IQ range: 0-176) vs. a median of 168 PVCs over 24 hours (IQ range: 3-531) in patients with successful and failed procedures. This cutoff (non-predominant PVC burden ≥156 over 24 hours) was then utilized as the definition of a patient with pleomorphic PVCs. The presence of pleomorphic PVCs was associated with a lower success rate independent on the site of origin of the predominant PVC (p=0.017). Table 2 compares characteristics of 31 and 69 patients with pleomorphic and monomorphic PVCs. A mean of 3.5±1.2 (range 2-6)

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morphologies of PVCs were present in patients with pleomorphic PVCs. Patients with pleomorphic versus monomorphic PVCs were less likely to have a successful procedure (71 vs. 90%, p=0.017). Patients with pleomorphic versus monomorphic PVCs were more likely to have an epicardial origin (29 vs. 9%, p=0.008) and were less likely to have an endocardial

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origin (52 vs. 74%, p=0.028) of the predominant PVC. Patients with pleomorphic PVCs had a trend towards an origin from the papillary muscles (13 vs. 4%, p=0.12).

A parahisian origin was more likely in patients with unsuccessful ablation (19 vs. 5%,

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n=3/16 vs. n=4/84, p=0.044). Ablation was limited due to the risk of conduction

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abnormalities in the 3 patients with unsuccessful ablation.

Repeat procedures

Twenty patients (20%) had repeat procedures for recurrent frequent PVCs at our medical center (Table 3, 6 / 20 patients had pleomorphic PVCs). Six/20 patients (30%) had

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an unsuccessful first procedure while the remaining 14 patients (70%) had a delayed recurrence of PVCs. The time to symptom recurrence after the initial procedure was a mean of 30.3 ± 13.3 months. The mean interval between the initial and most recent procedure was

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34.4 ± 24.5 months. The predominant PVC in repeat ablation procedures was the previously

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targeted predominant PVC (Figure 1, n=16, 80%). In 3 patients (15%), the PVCs were previously non-predominant PVCs that increased in frequency and in 1 patient (5%) a new PVC morphology was found. The PVC sites of origin for the non-predominant PVCs that were targeted during repeat ablation were the anterolateral papillary muscle, the posteromedial papillary muscle, and the epicardial left ventricular outflow tract. The new PVC originated from the parahisian region.

Follow-up Quantification of Non-predominant PVCs

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There were 23 patients with pleomorphic PVCs who underwent successful ablation of the predominant PVC and had a non-targeted PVC. A non-predominant PVC was targeted for ablation in 7 of 23 patients (30%) and was successful in 3 patients. The PVC burdens preand post-ablation are presented in Table 4. The overall PVC burden decreased from 19.8 ±

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9.8% to 3.1 ± 4.6% at follow-up (p<.0001). There was no change in the non-predominant PVC burden from pre-ablation to follow-up (Figure 2, 1.8 ± 2.6 to 2.1 ± 4.6%, p=0.77).

Among the 23 patients with pleomorphic PVCs who underwent successful ablation of

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the predominant PVC, 3 (13.0%) and 2 (8.7%), respectively had a doubling in nonpredominant PVC burden to at least 1 and 5% of the overall ventricular beats. Neither the site

non-predominant PVC burden.

Discussion:

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Main Findings

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of origin, coupling interval, nor baseline PVC burden was predictive of an increase in the

The main finding of this study is that the presence of pleomorphic PVCs with a cutoff of ≥ 156 PVCs/24 hours adversely affects ablation success. Despite the lower ablation

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success in patients with pleomorphic PVCs, the burden of non-predominant PVCs is most

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often stable during follow-up. Furthermore, most repeat PVC ablations are due to reemergence of previously targeted predominant PVCs, not an increase in the previously nonpredominant PVCs and not due to previously undocumented PVCs.

Pleomorphic PVCs Definition and Outcomes Pleomorphic PVCs are frequent and in this series were present in almost one third of patients without structural heart disease. Pleomorphic PVCs have been previously reported to be associated with PVC mediated cardiomyopathy.6,7 Although the presence of more than one

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PVC morphology has been associated with decreased ablation success, longer procedure times, and longer radiofrequency ablation times2, the cutoff number of non-predominant PVCs that adversely affects outcomes was previously uncertain. A frequency of nonpredominant PVCs of ≥156 beats best differentiated effective from ineffective PVC ablation

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procedures. Patients with pleomorphic PVCs should be aware of the lower success rate of approximately 70%.

There were more epicardial and papillary muscle PVCs as the predominant PVCs in

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patients with pleomorphic PVCs compared to patients with monomorphic PVCs. Both of these sites of origin are associated with a success rate of approximately 70%8,9. This

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association has been described in prior studies10. Pleomorphic PVCs are associated with a lower success rate independent of the site of origin. It is possible that the arrhythmic substrate in patients with epicardial and papillary muscle PVCs is somewhat different from patients with PVCs originating from the endocardium. The possibility of a single focus

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generating different morphologies may apply to papillary muscle PVCs, but most of the predominant PVCs in the pleomorphic PVC group originated from the outflow tract.

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Pleomorphic PVCs and Recurrences

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We hypothesized that recurrence of PVCs in patients with pleomorphic PVCs would be due to a rise in PVC burden from non-predominant PVC sites and that the coupling interval might be longer in non-predominant PVCs than the predominant PVCs. Thus, with elimination of the predominant PVC, the non-predominant PVC burden could increase. Interestingly, the burden of the non-predominant PVCs most often was stable during followup and the ablation procedure often was successful even when not all PVCs were targeted. Most repeat PVC ablations were due to a rise in burden of a previously predominant PVC rather than an increase in non-predominant PVCs or new PVCs. However, in 15% of patients

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with recurrences, the predominant PVC was originally a non-predominant PVC. No variables predictive of an increase in the burden of a previously infrequent PVC could be identified.

Limitations

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There is the possibility of referral bias as this study was performed at a tertiary medical center and 30% of the patients had undergone prior ablation elsewhere. Determination of the site of origin for some non-predominant PVCs not targeted for mapping

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and ablation was accomplished by ECG criteria. We used previously utilized definitions of endocardial, intramural, and epicardial site of origin. There is continuity between the layers

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of myocardium and current technology does not allow for exact determination of the depth of source for the PVCs. We classified PVCs with slight variations in ECG morphology as coming from a single site of origin. It is possible that in some instances this PVC originated from a different site of origin. Similarly, we cannot exclude the possibility that a non-

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predominant PVC represented a different exit site from the predominant PVC source. We utilized a broader definition inclusive of slight changes in ECG configuration to lower this possibility. Furthermore, the finding that the non-predominant PVCs were usually present

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post-procedure supports that they arose from a distinct site of origin.

Conclusion

In the presence of pleomorphic PVCs, elimination of the predominant PVC most

often results in a successful ablation, even if not all PVCs are targeted. An untargeted infrequent PVC usually does not increase in burden or necessitate a redo ablation procedure during follow-up.

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ACCEPTED MANUSCRIPT References:

1.

Baser K, Bas HD, Belardi D, et al. Predictors of outcome after catheter ablation of

premature ventricular complexes. J Cardiovasc Electrophysiol 2014;25:597-601. Latchamsetty R, Yokokawa M, Morady F, et al. Multicenter Outcomes for Catheter

Ablation

of

Idiopathic

Premature

Ventricular

Complexes.

Electrophysiology 2015;1:116-23.

JACC:

Clinical

Baman TS, Lange DC, Ilg KJ, et al. Relationship between burden of premature

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3.

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2.

ventricular complexes and left ventricular function. Heart Rhythm 2010;7:865-9. Yokokawa M, Desjardins B, Crawford T, Good E, Morady F, Bogun F. Reasons for

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4.

recurrent ventricular tachycardia after catheter ablation of post-infarction ventricular tachycardia. Journal of the American College of Cardiology 2013;61:66-73. 5.

Yokokawa M, Morady F, Bogun F. Injection of cold saline for diagnosis of

6.

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intramural ventricular arrhythmias. Heart Rhythm. 2016;13:78-82. Bas HD, Baser K, Hoyt J, et al. Effect of circadian variability in frequency of

2016;13:98-102.

Sadron Blaye-Felice M, Hamon D, Sacher F, et al. Premature ventricular

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premature ventricular complexes on left ventricular function. Heart Rhythm

contraction-induced

cardiomyopathy:

Related

clinical

and

electrophysiologic

parameters. Heart Rhythm 2016;13:103-10. 8.

Baman TS, Ilg KJ, Gupta SK, et al. Mapping and ablation of epicardial idiopathic

ventricular arrhythmias from within the coronary venous system. Circ Arrhythm Electrophysiol 2010;3:274-9.

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Yokokawa M, Good E, Desjardins B, et al. Predictors of successful catheter

ablation of ventricular arrhythmias arising from the papillary muscles. Heart Rhythm 2010;7:1654-9. 10.

Latchamsetti R, Yokokawa M, Morady F, et al. Multicenter Outcomes for Catheter

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Ablation of Idiopathic Premature Ventricular Complexes. JACC EP 2015;1:116-23.

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Table 1 – Patient Characteristics (n=100)

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Age (years) 52 ± 15 Male Sex 53 (53) Comorbidities Coronary artery disease 5 (5) Hypertension 41 (41) Diabetes mellitus 8 (8) Stroke 5 (5) Hyperlipidemia 30 (30) Valve disease 3 (3) Prior coarctation repair 1 (1) Prior PFO or ASD s/p 2 (2) percutaneous closure Medications Beta-blocker 47 (47) Diltiazem or Verapamil 13 (13) Flecainide or Propafenone 13 (13) Mexiletine 1 (1) Sotalol 2 (2) Amiodarone 2 (2) Site of Predominant PVC site of origin Endocardial 67 (67) Intramural 18 (18) Epicardial 15 (15) Predominant PVC Region (include in table) Outflow tract 73 (73) Papillary Muscle 7 (7) Parahisian 7 (7) Mitral annulus 5 (5) Fascicular 3 (3) Other 5 (2 were MCV) Echocardiographic Data Baseline LV end-diastolic 51 ±6.5 diameter (mm) Baseline LV EF (%) 57 ± 9 ASD, Atrial septal defect; EF, Ejection fraction; LV, Left ventricle; MCV, Middle cardiac vein; PFO, Patent foramen ovale; PVC, Premature ventricular contraction

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Table 2. Characteristics of patients with monomorphic vs. pleomorphic PVCs Monomorphic Pleomorphic p-value (n=69) (n=31) Age (years) 51 ± 14 54 ± 17 0.29 Male Sex 41 (59) 12 (39) 0.055 Comorbidities Coronary artery disease 2 (3) 3 (10) 0.15 Hypertension 29 (42) 12 (39) 0.75 Diabetes mellitus 3 (4) 5 (16) 0.045 Stroke 5 (7) 0 (0) 0.12 Hyperlipidemia 22 (32) 8 (26) 0.54 Valve disease 2 (3) 1 (3) 0.95 Pacemaker 2 (3) 0 (0) 0.34 ICD 2 (3) 1 (3) 0.93 PVC Burden 17.6 ± 12.5 19.9 ± 11.3 0.80 Overall burden (%) Site of Predominant PVC site of origin Endocardial 51 (74) 16 (52) 0.028 Intramural 12 (17) 6 (19) 0.81 Epicardial 6 (9) 9 (29) 0.008 Predominant PVC Region (include in table) Outflow tract 53 (77) 20 (65) 0.20 Papillary Muscle 3 (4) 4 (13) 0.12 Parahisian 5 (7) 2 (6) 0.89 Mitral annulus 4 (6) 1 (3) 0.59 Fascicular 1 (1) 2 (6) 0.18 Other 3 (4) 2 (6) 0.66 Procedural Details Repeat Procedure 14 (20) 6 (19) 0.91 Successful ablation 62 (90) 22 (71) 0.017 Echocardiographic Data Baseline LV end- 51 ± 7 52 ± 6 0.80 diastolic diameter (mm) Baseline LV EF (%) 57 ± 10 55 ± 29 0.32 EF, Ejection fraction; ICD, Implantable cardioverter-defibrillator; LV, Left ventricle; PVC, Premature ventricular contraction

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5

PMP

207

No

38.6

6

Endocardial OFT

9

Yes

6.7

7

Parahisian

0

Yes

10.3

57

Yes

23.2, 23.7, and 37.1

58

Yes

292

Yes

180

No

194

No

0

No

12 13 14 15 16 17 18

Non-predominant

N/A N/A

N/A GCV (Epicardial OFT)

36.2

Previously predominant PVC

N/A

69.3

Previously predominant PVC

N/A

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N/A

Return of previously predominant PVC Return of previously predominant PVC Return of previously predominant PVC Return of previously predominant PVC Return of previously predominant PVC Non-predominant

58.3

13.3

N/A N/A N/A N/A N/A PMP

Yes

31.9

Return of previously predominant PVC

N/A

Yes

44.4

New

Parahisian

Yes

95.1

138

Yes

42.9

13

No

42.0

0 0 0

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Intramural OFT Epicardial OFT ALP and PMP ALP Intramural OFT Epicardial OFT Epicardial OFT Endocardial MA Endocardial OFT Endocardial OFT Endocardial OFT

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2nd procedure origin (if not same)

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Table 3. Detail on patients with multiple procedures at our institution Patient # Initial # of Procedure Interval 2nd procedure reason procedure pleomorphic Success between predominant PVCs procedures origin (months) Tricuspid Return of previously 1 0 Yes 7.7 annulus predominant PVC Intramural 45.9, 63.8, Return of previously 2 0 Yes OFT 68.2 predominant PVC Epicardial 3 882 No 12.0 Previously predominant PVC OFT Endocardial Return of previously 4 7 Yes 16.3 OFT predominant PVC

19

Parahisian

134

Yes

6.6

20

Epicardial OFT

1805

Yes

15.0

Return of previously predominant PVC Return of previously predominant PVC Non-predominant Return of previously predominant PVC Return of previously predominant PVC

N/A N/A ALP N/A N/A

ALP, Anterolateral papillary muscle; GCV, Great cardiac vein; MA, Mitral annulus; N/A, Not applicable; OFT, Outflow tract; PMP, Posteromedial papillary muscle; PVC, Premature ventricular contraction

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Table 4. Serial PVC burden assessment in patients with pleomorphic PVCs that underwent successful ablation of the predominant PVC and had a non-targeted PVC (n=23) Pre-ablation Follow-up p-value (%) (%) Overall PVC burden 19.8 ± 9.8 3.1 ± 4.6 <.0001 Predominant PVC 18.0 ± 9.6 0.6 ± 1.3 <.0001 Non-Predominant 1.8 ± 2.6 2.1 ± 4.6 0.77 PVCs Non-Predominant 1 1.0 ± 1.1 2.0 ± 4.6 0.31 Non-Predominant 2 0.7 ± 2.2 0.04 ± 0.1 0.14 New PVCs N/A 0.5 ± 1.6 N/A N/A, Not applicable; PVC, Premature ventricular contraction;

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ACCEPTED MANUSCRIPT Figure Legend: Figure 1. Predominant source of PVCs for repeat ablation patients (n=20)

Figure 2. Individual patient change in non-predominant PVC burden pre-ablation and at follow-up

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(n=23)

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