Value of cardiac magnetic resonance imaging and programmed ventricular stimulation in patients with frequent premature ventricular complexes undergoing radiofrequency ablation

Accepted Manuscript Value of Cardiac Magnetic Resonance Imaging and Programmed Ventricular Stimulation in Patients with Frequent Premature Ventricular Complexes Undergoing Radiofrequency Ablation Miki Yokokawa, MD, Konstantinos C. Siontis, MD, Hyungjin Myra Kim, ScD, Jadranka Stojanovska, MD, MS, Rakesh Latchamsetty, MD, Thomas Crawford, MD, Krit Jongnarangsin, MD, Hamid Ghanbari, MD, Ryan Cunnane, MD, Aman Chugh, MD, Frank Pelosi, Jr., MD, Hakan Oral, MD, Fred Morady, MD, Frank Bogun, MD PII:

S1547-5271(17)30842-1

DOI:

10.1016/j.hrthm.2017.06.040

Reference:

HRTHM 7227

To appear in:

Heart Rhythm

Received Date: 26 March 2017 Revised Date:

1547-5271 1547-5271

Accepted Date: 1547-5271 1547-5271

Please cite this article as: Yokokawa M, Siontis KC, Kim HM, Stojanovska J, Latchamsetty R, Crawford T, Jongnarangsin K, Ghanbari H, Cunnane R, Chugh A, Pelosi Jr F, Oral H, Morady F, Bogun F, Value of Cardiac Magnetic Resonance Imaging and Programmed Ventricular Stimulation in Patients with Frequent Premature Ventricular Complexes Undergoing Radiofrequency Ablation, Heart Rhythm (2017), doi: 10.1016/j.hrthm.2017.06.040. 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.

ACCEPTED MANUSCRIPT 1

Value of Cardiac Magnetic Resonance Imaging and Programmed Ventricular Stimulation

Radiofrequency Ablation

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in Patients with Frequent Premature Ventricular Complexes Undergoing

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Miki Yokokawa, MD, Konstantinos C. Siontis, MD, Hyungjin Myra Kim, ScD,

Jadranka Stojanovska, MD, MS, Rakesh Latchamsetty, MD, Thomas Crawford, MD,

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Krit Jongnarangsin, MD, Hamid Ghanbari, MD, Ryan Cunnane, MD, Aman Chugh, MD, Frank Pelosi, Jr, MD, Hakan Oral, MD, Fred Morady, MD, Frank Bogun, MD

Division of Cardiovascular Medicine (MK, KCS, HMK, RL, TC, KJ, HG, RC, AC, FP, HO, FM,

Conflict of interest: none

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FB) and Department of Radiology (JS), University of Michigan, Ann Arbor, MI, USA.

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Drs. Yokokawa and Siontis equally contributed to the manuscript.

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Running title: PVC ablation and Risk stratification Word count: 4826

Address for correspondence: Frank Bogun, MD Cardiovascular Center, SPC 5853, 1500 East Medical Center Drive, Ann Arbor, Michigan 48109-5853 Tel: 734 763 7141 Fax: 734 936 7026 E-mail: [email protected].

ACCEPTED MANUSCRIPT 2 ABSTRACT Background: Frequent premature ventricular complexes (PVC) have been associated with increased mortality. However, the optimal approach to the risk stratification in these patients is

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unclear.

Objective: The purpose of this study was to prospectively assess the use of cardiac magnetic resonance imaging (MRI) and programmed ventricular stimulation to identify patients with

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PVCs undergoing radiofrequency ablation at risk for adverse long-term outcomes.

Methods: A total of 321 consecutive patients (52±15 years; males: 157 [49%], left ventricular

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ejection fraction: 51±12%) underwent PVC ablation between 2004 and 2015 preceded by a cardiac MRI to assess for structural heart disease (SHD). Programmed stimulation was performed at the time of the ablation procedure. If ventricular tachycardia (VT) was induced in the presence of SHD, a cardioverter-defibrillator (ICD) was implanted.

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Results: SHD was identified by MRI in 64 patients (20%) and sustained monomorphic VT was inducible in 15 patients (5%). Fourteen patients had both SHD and inducible VT, and received an ICD after the procedure. The primary endpoint of VT/VF or death was met in 15 patients after

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a median 20 months of follow-up. The combination of SHD by MRI and VT inducibility conferred independently an increased risk of adverse outcome (multivariate hazard ratio 25.73,

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95% confidence interval 6.74-98.20, P<0.001). Conclusion: Pre-ablation cardiac MRI and programmed stimulation can be useful for risk stratification in patients with frequent PVCs. Patients with inducible VT in the setting of SHD may benefit from ICD implantation after ablation regardless of the left ventricular ejection fraction.

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Key words: Premature ventricular complexes (PVC), ventricular tachycardia (VT), risk stratification, cardiac magnetic resonance imaging (MRI), programmed ventricular stimulation,

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structural heart disease

ACCEPTED MANUSCRIPT 4 Introduction Frequent premature ventricular complexes (PVCs) can induce a cardiomyopathy that may be reversible with radiofrequency ablation1. Patients with frequent PVCs also have an increased 2

which may be attributable to the presence of concomitant structural heart

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risk of mortality

disease (SHD). The approach to the risk stratification for sudden cardiac death (SCD) in this patient population is not well defined. We prospectively performed cardiac magnetic resonance

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imaging (MRI) and programmed ventricular stimulation in patients undergoing catheter ablation

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for frequent PVCs to evaluate their value for risk stratification in this patient population.

Methods Patient Characteristics

A total of 321 consecutive patients with frequent PVCs (mean age: 52±15 years; males:

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157 [49%], left ventricular [LV] ejection fraction: 51±12%) underwent PVC ablation between 2004 and 2015 preceded by a cardiac MRI (Table 1). The supplemental material indicates the

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patients characteristics.

Pre-procedural Testing

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A cardiac MRI and a preprocedural Holter were performed in all patients. Specific

information about preprocedural testing is indicated in the supplementary material.

Electrophysiology Procedure / Ablation The study was approved by the institutional review board of the University of Michigan. Procedural details are specified in the supplemental material.

ACCEPTED MANUSCRIPT 5 Definitions: Inducible VT: monomorphic, sustained VT lasting longer than 30 seconds or requiring intervention (overdrive pacing or cardioversion) for termination. No specific cut-off cycle length

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was used for this definition. Polymorphic VT or VF were not considered as a specific result of programmed stimulation. ICDs were not implanted in patients who had only inducible VF or

Implantation of Implantable Cardioverter Defibrillator

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polymorphic VT.

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Details about implantation of implantable cardioverter defibrillator and the overall protocol (Figure 1) are included in the supplemental material.

Post-ablation Follow-up

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The first PVC ablation procedure at our institution was considered to be the index procedure and start of follow-up. An echocardiogram and a Holter monitor were performed 3 months post ablation. Patients were seen in follow-up 3-6 months post-ablation and then every

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12-48 months thereafter. Patients with an ICD were followed in the device clinic every 3-6 months. If the LV ejection fraction failed to improve in the setting of a successful or failed

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ablation procedure, an ICD was implanted during follow-up, at the discretion of the attending electrophysiologist and the referring physician. The primary endpoint of the study was VT/VF or all-cause mortality, whichever occurred first. In patients with ICDs, all ICD tracings were available for adjudication of VT/VF.

Statistical Analysis

ACCEPTED MANUSCRIPT 6 Continuous variables were expressed as mean ± 1 standard deviation (or median and interquartile range for non-normally distributed variables) and were compared by the Student’s ttest between patients with and without SHD, and patients with and without inducible VT.

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Categorical variables were compared using the χ2 test, but if the expected count was smaller than 5 in a given cell of the 2 x 2 table, the Fisher’s exact test was used. For the purpose of outcomes analysis, patients were at first categorized into four mutually exclusive groups based

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on presence of SHD and VT inducibility (no SHD and no inducible VT; no SHD and inducible

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VT; SHD and no inducible VT; SHD and inducible VT), and the second group of those without SHD and with inducible VT was excluded from the analysis due to small sample size. KaplanMeier curves and the log-rank test were used to compare the time from ablation to the primary endpoint of VT/VF or death in these groups. The associations of individual demographic and clinical variables with the primary endpoint were summarized using crude hazard ratios derived

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by univariate Cox regression models. A multivariable Cox regression model assessed whether SHD and VT inducibility were predictive of the primary endpoint. Dummy variables were created to indicate the aforementioned groups based on the presence of SHD and VT inducibility

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at baseline, using the no SHD/no inducible VT group as the reference group. Adjustments were made for age, gender and additional covariates that were identified by a backward stepwise

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selection process eliminating variables without statistically significant association at the P=0.10 level. The following variables were assessed for inclusion in the multivariable model: baseline LV ejection fraction, hypertension, hyperlipidemia, diabetes mellitus, atrial fibrillation, renal insufficiency, chronic obstructive pulmonary disease, and ablation success. Two-tailed 0.05 level tests were used for statistical significance.

ACCEPTED MANUSCRIPT 7 Results

Cardiac MRI Findings

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Among the 321 patients who underwent cardiac MRI before the ablation procedure, in 7 patients (2%) the MRI was performed without gadolinium because of severe renal dysfunction. Sixty-four of the 321 patients (20%) had SHD, and 257 had no SHD (80%). LGE was identified

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in 60 patients (19%) and was in a pattern consistent with prior myocardial infarction in 21 patients (35%) and non-ischemic cardiomyopathy in 39 patients (65%). Structural abnormalities

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other than or in addition to LGE were identified in 7 patients (2%) including right ventricular dilation and dyskinesis in 3 patients, LV non-compaction in 3 patients, and congenital LV aneurysm in 1 patient. Patients with SHD were older, more frequently male, and had lower LV ejection fraction before and after ablation compared to patients without SHD. Patients with SHD

Electrophysiology Study

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also had a smaller degree of PVC burden improvement post-ablation (Table 2).

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Isoproterenol was administered in 304 patients (95%) during the EP study. Despite the use of isoproterenol infusion up to 20 mcg/min, no PVCs were observed in 2 patients. With

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programmed stimulation, 15 of 321 patients (5%) had inducible monomorphic sustained VT (with isoproterenol infusion in 1 patient) (Supplemental Figure 1,2). A monomorphic sustained VT was induced in 3 of 53 patients (6%) who were referred after a prior unsuccessful ablation. A total of 29 sustained, monomorphic VTs were inducible (mean 1.9±1.7 per patient). In 9 of 15 patients (60%), only 1 VT was inducible. Multiple VTs were induced in the remaining 6 patients (Supplementary Table 1). The mean VT cycle length was 250±55 msec. Thirteen VTs had a left

ACCEPTED MANUSCRIPT 8 bundle branch block and 16 had a right bundle branch block morphology. Six induced VTs had the same morphology as the predominant PVC. In 8 of 15 patients whose VT was inducible before ablation, VT was no longer inducible after the ablation. VF was induced in 10 patients

VT was inducible in addition to VF and an ICD was implanted.

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(3%) with stimulus coupling intervals ≤230 msec. In 3 of 10 patients, sustained, monomorphic

Patients who had inducible VT had a lower LV ejection fraction at baseline compared to

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the other patients (43±16% vs 52±12%, P=0.009) (Table 3). With respect to the PVC QRS morphology, and site of origin, there was no significant difference between patients with and

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without inducible VT (Table 3). The ejection fraction in patients with inducible VT improved post-ablation to 54±13% (P=0.06). In addition, patients with inducible VT more often had SHD by MRI compared to the patients without inducible VT (93% vs. 16%, P<0.001). Of the 15 patients with inducible VT, only one had no evidence of SHD, 11 patients had evidence of LGE,

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2 patients had right ventricular dilation and dyskinesis consistent with ARVC, and 2 patients had LV non-compaction (Supplemental Table 2). Three patients met Task Force criteria for ARVC3. The distribution of patients in the 4 groups defined by the presence of SHD and VT

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inducibility was as follows: 257 patients in the group without SHD and without inducible VT, 1 patient in the group without SHD and with inducible VT, 49 patients in the group with SHD and

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without inducible VT, and 14 patients in the group with SHD and inducible VT. In the latter group, 5 (36%) patients had a prior history of myocardial infarction.

Ablation Outcomes PVCs were successfully ablated acutely in 248 of 321 patients (77%). In 79 patients (25%) the PVCs originated from the right ventricular outflow tract, in 31 patients (10%) from the

ACCEPTED MANUSCRIPT 9 aortic sinus cusps, in 55 (17%) from the LV epicardium, in 43 (13%) from the papillary muscles, and from elsewhere in 113 patients (35%). In 19 of 60 patients (32%) in whom LGE was identified, the site of origin was in a low voltage area (bipolar voltage <1.5 mV). Scar-related

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PVCs were identified in 6 of 15 patients (40%) with inducible VT and 13 of 306 patients (4%) without inducible VT (P<0.001). The PVC burden was decreased from 20±13% to 4±9% (P<0.0001) and the LV ejection fraction improved from 51±12% to 57±9% (P<0.0001) 3-6

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months after the ablation.

An ICD was implanted in 14 patients with inducible VT and SHD. A successful VT

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ablation was performed in 1 patient with inducible VT but without SHD in whom the site of origin of the PVC and the VT were identical (RVOT). An ICD was not implanted in that patient. In 2 patients with ARVC and inducible VT from the RVOT, an ICD was implanted. In two patients, an ICD was implanted later during follow-up after the LV ejection fraction failed to

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improve >35% after ablation.

Follow-up and Clinical Outcomes

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In the 14 patients who underwent ICD implantation post-ablation due to inducible VT and SHD, 7 patients had VT/VF at a median of 20 (IQR 1-49) months after the ablation

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procedure. VT also occurred in one of the two patients in whom an ICD was implanted after the LV ejection fraction failed to improve post-ablation. Furthermore, VF and SCD occurred in 1 patient with scarring on the MRI after a surgical ablation for WPW in 1989. This patient had no inducible VT at the ablation procedure and had a pacemaker for sinus node dysfunction. His ejection fraction post ablation was 50%. There was no documented recurrence of pre-excitation post-operatively before the SCD.

ACCEPTED MANUSCRIPT 10 Two of the 7 patients with inducible VT and subsequent clinical VT/VF died. In addition, the patient with primary prevention ICD and VT, and another 7 patients died during follow-up. Thus, the primary endpoint of VT/VF or death occurred in 15 (4.7%) patients during a median

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follow-up of 20 months (IQR 4-49). Of the 10 patients who died, the 2 patients in whom VT was inducible died with worsening heart failure; among the 8 patients without inducible VT, 1 patient had SCD, 1 patient died from progressive heart failure (this patient had an ICD implanted after

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the ejection fraction failed to improve post ablation and also had appropriate ICD therapy), and 6 patients died from other causes (cancer n=2, hepatic failure n=1, respiratory failure n=1, accident

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n=1, unknown n=1). Among the 8 patients with prior revascularization, 3 patients had inducible VT and underwent ICD implantation, one of which had VT after 492 days of follow-up. The other 7 patients with prior revascularization had no clinical events at most recent follow-up. The patients who had VT/VF or died from any cause were older, had lower LVEF, more

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often had atrial fibrillation and renal insufficiency compared to patients without such adverse events (Supplemental Table 3). The prevalence of SHD on MRI was significantly higher in patients with adverse outcome than those without adverse outcome. Similarly, VT inducibility at

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the beginning or at the end of the procedure was more frequent among patients with adverse outcome. The presence of multiple induced VTs was not associated with worse prognosis

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compared to single induced VT. Among the 8 patients with inducible VT pre-ablation that were rendered non-inducible at the end of the procedure, 3 patients had VT/VF during follow-up. Among the different groups of patients defined by SHD and VT inducibility pre-ablation,

the primary endpoint of VT/VF and death was met by 6/257 patients with no SHD/no inducible VT (event rate of 0.0052 per year), 0/1 patients in those with no SHD/inducible VT (event rate of 0 per year), 2/49 patients in those with SHD/no inducible VT (event rate 0.0102 per year), and

ACCEPTED MANUSCRIPT 11 7/14 patients with SHD/inducible VT (event rate 0.192 per year). Survival free of VT/VF and death was significantly different in the 3 groups (Figure 2; log-rank P<0.01), after excluding the group with no SHD/inducible VT (n=1). With respect to only VT/VF, the event rate was 1/257

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(0.00086 per year) for patients with no SHD / no inducible VT; 0/1 (0 per year) for patients with no SHD / inducible VT; 1/49 (0.0051 per year) for patients with SHD / no inducible VT; and 7/14 (0.192 per year) for patients with SHD / inducible VT. Adjusting for age, gender, baseline

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LV ejection fraction, atrial fibrillation and renal insufficiency, the group with both SHD and inducible VT had significantly worse survival free of VT/VF or death compared with the

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reference group of patients that had neither SHD nor inducible VT (adjusted hazard ratio 25.73, 95% confidence interval 6.74-98.20, P<0.001). The adjusted HR for those with SHD and no inducible VT was 2.36 (95% CI 0.51-10.99, P=0.27). The results were similar when we excluded the 7 patients in whom the MRIs were performed without gadolinium from the analysis, and

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when we further adjusted in the multivariate model for the post-ablation EF. Finally, when considering only cardiac deaths in the composite outcome, the 3 groups had significantly different survival free of VT/VF or cardiac death, with the group with SHD/inducible VT having

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the highest risk of adverse events (log-rank P<0.01; Supplementary Figure 3). The smaller number of events for the composite outcome of VT/VF or cardiac death did not allow us to

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calculate HRs and 95% CIs for this outcome.

Discussion

Main findings

Pre-procedural cardiac MRI helps to identify patients with SHD and programmed ventricular stimulation helps to identify the patients in whom the risk of adverse outcome

ACCEPTED MANUSCRIPT 12 including SCD is increased. Programmed ventricular stimulation should be strongly considered in patients with frequent PVCs in the presence of SHD since about a quarter of these patients have inducible, sustained monomorphic VT and hence may be at risk for dying suddenly.

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Patients with inducible VT in the setting of SHD appear to benefit from ablation of the induced

Association of Frequent PVCs and Increased Mortality

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VTs and ICD implantation.

Frequent PVCs have long been thought to be associated with a low risk of mortality

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especially in the absence of apparent heart disease 4. A meta-analysis of patients without known SHD demonstrated an increased risk of adverse events that was attributed to the presence of occult heart disease 5. Our study confirms this by using cardiac MRI systematically in patients undergoing ablation procedures for frequent PVCs. Frequent PVCs may be associated with

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increased mortality in patients with prior myocardial infarction, but it is unknown whether this increased mortality is attributable to an increased risk of SCD 6. The risk of SCD in patients with non-ischemic cardiomyopathy and frequent PVCs has 8

in which amiodarone was

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been reported7 and was further studied in the CHF-STAT trial

compared to placebo. Amiodarone effectively suppressed PVCs and resulted in an improvement

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in the ejection fraction. Despite a beneficial effect on the ejection fraction, there was no reduction in mortality in the amiodarone arm. The CHF-STAT trial and also the CAST trial demonstrated that although PVCs identify a population at risk for SCD, suppression of PVCs does not reduce the risk. After successful ablation of PVCs in the present study, even in the presence of SHD, the ejection fraction in most patients normalized. Normalization of ejection fraction, however, even in these patients may not reduce the risk for adverse outcome.

ACCEPTED MANUSCRIPT 13 Frequent PVCs in the absence of coronary artery disease can be associated with ARVC and a PVC burden >500 PVCs / 24 hours is one of the criteria for ARVC. In this series, 3

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patients with frequent PVCs met the Task Force criteria 9 for ARVC and had inducible VT.

Risk Stratification and Frequent PVCs

The presence of SHD on MRI, in particular scarring, identifies patients at risk for adverse 10

and for patients with

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outcome. This is the case for patients with prior myocardial infarction

non-ischemic cardiomyopathy11 even in the presence of preserved left ventricular function12.

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Inducibility of VT by programmed ventricular stimulation also identifies patients with prior myocardial infarction who are at increased risk of SCD

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. The inducibility of VT in

patients with non-ischemic cardiomyopathy also identified patients at increased risk for recurrent ICD therapy in the DEFINITE trial. LGE-MRI and programmed stimulation have subsequently 14

and non-ischemic cardiomyopathy 15. The use of

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been used for risk stratification in ischemic

LGE-MRI and programmed stimulation in the present study in patients with frequent PVCs identified a patient population at increased risk of adverse events. The presence of PVCs alone

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may be an indicator of a higher risk population; this, however, is speculative because all patients

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in this study had frequent PVCs.

PVC-induced Cardiomyopathy and Mortality Radiofrequency ablation of PVCs has been shown to improve the ejection fraction in

patients with frequent PVCs. This is the case even in the presence of SHD16. Therefore, PVC ablation may obviate the need for ICD implantation for primary prevention of SCD if the ejection fraction improves to >35%. A recent multicenter study demonstrated that the majority of

ACCEPTED MANUSCRIPT 14 patients meeting ICD implantation criteria for primary prevention of SCD did not meet implantation criteria after successful catheter ablation17. Although these results were encouraging, there was no risk stratification performed to assess whether some of these patients were still at

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increased risk for SCD. It is unclear how many patients with underlying SHD were included in this study because cardiac MRIs were not performed beforehand. Also, programmed ventricular stimulation was not performed in these patients. An improvement in ejection fraction, as

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demonstrated in the CHF-STAT study, does not necessarily reduce the risk of SCD or cardiac mortality.

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Our data indicate that patients at increased risk for SCD can be identified by cardiac MRI and programmed ventricular stimulation. Therefore, programmed ventricular stimulation should be performed during an ablation procedure in patients with frequent PVCs, especially in the presence of SHD. In multivariate analysis, the combination of SHD and VT inducibility was an

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independent and powerful predictor of adverse outcome. In contrast, adverse events were relatively rare in the group with SHD but no inducible VT. It is unclear whether the presence of abnormal LV function at the time of an ablation

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procedure predisposes patients to an increased risk of SCD in the absence of SHD. This does not appear to be the case, provided that the ablation procedure is effective and results in

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normalization of the ejection fraction. If VT is inducible in these patients, it often has the morphology of the targeted PVCs and can be eliminated by ablation. However, if frequent PVCs are not eliminated and the ejection fraction remains low, an ICD implantation should be considered.

Limitations

ACCEPTED MANUSCRIPT 15 A control group without PVCs is required to determine whether the results of this study were independent of the frequent PVCs and reflected only the presence of SHD and/or inducible VT. Secondly, the value of programmed ventricular stimulation can be limited by non-

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reproducibility or non-inducibility even if patients have documented VT. There was only 1 patient with inducible VT in the absence of SHD in our study. Even though this patient had no adverse event, it remains unclear whether such patients are at increased risk for SCD or not. The

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patients in this study include patients with and without SHD in the presence of frequent PVCs. Because risk stratification has not been clarified for either patient population, the study design

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was specified for consecutive patients with frequent PVCs rather than for a subgroup of patients. Also, the presence of right ventricular delayed enhancement might have been missed in some patients since the inversion time used for scanning was based on nulling of the left and not the right ventricular myocardium. Finally, it should be acknowledged that termination of VT/VF

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with ICD therapies does not necessarily equate to SCD prevention and some patients may have received ICD therapies for VTs that would have otherwise been self-terminating.

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Conclusions

The presence of frequent PVCs requires a thorough assessment for SHD because

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approximately 20% have evidence of SHD detected by MRI. This assessment should go beyond the determination of ejection fraction and assessment for coronary artery disease and should include a dedicated cardiac MRI to assess for the presence of SHD. Programmed stimulation may add incremental prognostic value at the time of an ablation procedure to identify patients who may benefit from ICD implantation.

ACCEPTED MANUSCRIPT 16 References:

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3.

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2.

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ACCEPTED MANUSCRIPT 18 Table 1: Baseline Patient Characteristics (N = 321) Variable 157 (49)

Age (years)

52±15

Comorbidities 155 (48)

- Diabetes mellitus

48 (15)

- Hyperlipidemia

129 (40)

- Atrial fibrillation

38 (12)

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- Hypertension

17 (5)

- Renal insufficiency

22 (7)

51±12

Baseline LV ejection fraction ≤35% PVC burden (%)

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PVC-induced cardiomyopathy Symptoms - Palpitations - Syncope

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- Asymptomatic

- Beta-blockers

47 (15) 20±13

Nonsustained ventricular tachycardia

Medications

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- Chronic obstructive pulmonary disease

LV ejection fraction (%)

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Male

134 (42)

106 (33)

223 (69) 4 (1) 61 (19)

225 (70) 62 (19)

- Amiodarone

19 (6)

- Other antiarrhythmics

65 (20)

- ACEi / ARB

86 (27)

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- Calcium channel blockers

Data are shown as n (%) or mean ± 1 standard deviation. Abbreviations: LV= left ventricular; PVC= premature ventricular complex; ACEi = angiotensin converting enzyme inhibitor; ARB= angiotensin receptor blocker.

ACCEPTED MANUSCRIPT 19 Table 2: Characteristics of Patients With and Without SHD on Cardiac MRI No SHD

SHD (n=64) 61±12

Male gender

44 (69)

50±15

<0.001

114 (44)

<0.001

52±12

<0.001

58±6

<0.001

31 (12)

0.009

20±13

20±13

0.91

7.2±11.1

3.7±8.3

0.01

14 (22)

1 (1)

<0.001

LV ejection fraction (%) - Before ablation

46±14

- After ablation

51±12

Baseline LV ejection fraction

16 (25)

≤35%

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PVC burden (%) - Before ablation - After ablation Inducible VT

p-value

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Age (years)

(n=257)

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Variable

Data are shown as n (%) or mean ± 1 standard deviation. Abbreviations: LV= left ventricular;

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MRI= magnetic resonance imaging; PVC= premature ventricular complex; SHD= structural

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heart disease; VT= ventricular tachycardia.

ACCEPTED MANUSCRIPT 20 Table 3: Characteristics of Patients With and Without Inducible VT No inducible VT

(n=15)

(n=306)

Age (years)

59±12

52±15

Male gender

11 (78)

- Before ablation

43±16

- After ablation

54±13

Baseline LV ejection fraction ≤35%

4 (27)

- Left bundle branch block - Inferior axis

57±9

<0.001

0.62

2.8±6.4

4.4±9.2

0.49

6 (40)

183 (60)

0.13

10 (67)

235 (77)

0.37

TE D

PVC sites of origin

0.009

20±13

M AN U

PVC morphology

51±12

0.18

18±10

- After ablation

0.05

43 (14)

PVC burden (%) - Before ablation

0.06

146 (48)

SC

LV ejection fraction (%)

p-value

RI PT

Inducible VT

Variable

4 (27)

75 (25)

0.77

- Aortic sinus cusp

1 (6)

30 (10)

1.0

0

55 (18)

0.08

4 (27)

39 (12)

0.13

6 (40)

107 (35)

0.37

14 (93)

50 (16)

<0.001

- LV epicardium - Papillary muscle - Others

AC C

SHD on MRI

EP

- Right ventricular outflow tract

Data are shown as n (%) or mean ± 1 standard deviation. Abbreviations: as above, LV= left ventricular; MRI= magnetic resonance imaging; PVC= premature ventricular complex; SHD= structural heart disease; VT= ventricular tachycardia.

ACCEPTED MANUSCRIPT 21 FIGURE LEGENDS

Figure 1. Protocol for implantable cardioverter defibrillator implantation in patients undergoing

RI PT

cardiac magnetic resonance imaging prior to premature ventricular complex ablation. Figure 2. Kaplan-Meier curve for survival free of VT/VF or death in groups of patients defined by the presence of structural heart disease and inducibility of ventricular tachycardia at the

AC C

EP

TE D

M AN U

SC

beginning of premature ventricular complex ablation.

AC C

EP

TE D

M AN U

SC

RI PT

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AC C

EP

TE D

M AN U

SC

RI PT

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