SUCCESSFUL VENTRICULAR TACHYCARDIA ABLATION IN PATIENTS WITH ELECTRICAL STORM REDUCES RECURRENCES AND IMPROVES SURVIVAL

Authors: Pasquale Vergara MD PhD1, Roderick Tung MD2, Marmar Vaseghi MD PhD FHRS3, Chiara Brombin PhD4, David Frankel MD5, Luigi Di Biase MD PhD6, Koichi Nagashima MD7, Usha Tedrow MD MS7, Wendy S. Tzou MD8, William H. Sauer MD8, Nilesh Mathuria MD9, Shiro Nakahara MD PhD10, Kairav Vakil MD11, Venkat Tholakanahalli MD11, T. Jared Bunch, MD12, J. Peter Weiss MD12, Timm Dickfeld MD13, Rama Vunnam, MD13, Dhanunjaya Lakireddy14, J. David Burkhardt, MD15, Anna Correra MD1, Pasquale Santangeli, MD5, David Callans MD5, Andrea Natale MD15, Francis Marchlinski MD5, William G. Stevenson MD7, Kalyanam Shivkumar MD PhD3 and Paolo Della Bella MD1

Institutions: 1San Raffaele Hospital, Milan, Italy; 2University of Chicago Medical Center, Chicago, Illinois; 3UCLA Cardiac Arrhythmia Center, UCLA Health System, Los Angeles, CA; 4University Centre for Statistics in the Biomedical Sciences, Vita-Salute San Raffaele University, Milano, Italy; 5Perelman School of Medicine at the University of Pennsylvania, Philadelphia; 6Albert Einstein College of Medicine/Montefiore Medical Center, New York, New York; 7Brigham and Women’s Hospital, Boston, MA, 8University of Colorado, Aurora, CO, 9Baylor St. Luke’s Medical Center/ Texas Heart Institute, Houston, Texas; 10Dokkyo Medical University Koshigaya Hospital, Saitama, Japan, 11University of Minnesota Medical Center, Minneapolis VA Medical Center, Minneapolis, MN, 12Intermountain Heart Institute, Intermountain Medical Center, Murray, UT, 13University of Maryland Medical Center, Baltimore, MD, 14University of Kansas Medical Center, Kansas City, KS, 15 Texas Cardiac Arrhythmia Institute, St. David’s Medical Center; Austin, TX;

Corresponding author:

Pasquale Vergara MD, Ph-D

Arrhythmia Unit and Electrophysiology Laboratory,

Department of Cardiology and Cardiothoracic Surgery,

Ospedale S. Raffaele, Milano, Italy.

Fax: +39-02 26437326, Tel: +39-3282513828, email:

Supplementary Methods

Statistical methods

Age, gender, type of cardiomyopathy, LVEF, NYHA class, hypertension, hyperlipidemia, atrial fibrillation (AF), diabetes mellitus, chronic kidney disease, occurrence of previous VT ablations, result of PES after the ablation, interaction terms and ES were included in the Cox regression model as covariates. Prior to apply the Cox regression model, we checked whether or not ES pts stratified by ablation outcome differed in terms of other baseline characteristics. In particular, we found that PES patients were different with respect to LVEF (Kruskal Wallis p-value= 0.0043, with the “No Inducible VTs” group and the “Nonclinical VTs inducible” group resulting significantly different from each other in the Dunn-Bonferroni post hoc analysis) and for having reported or not [experienced] a previous ablation (X2 p-value 0.0384). Hence, in addition to main effects, we entered in the multivariate Cox model also interaction terms to account for possible differential effect of LVEF and previous ablation on VT recurrence and survival outcome, depending on the PES group considered (hence PES*LVEF interaction, as well as PES*Previous ablation interaction, were specified in the model). The final model was obtained by applying stepwise procedures implemented in R, which evaluates improvements in the Akaike Information Criterion (AIC) when removing/adding individual terms from the full model to select the model10. The lower the AIC, the better the model.

Ablation procedure

Programmed electrical stimulation (PES) using up to two sites, two drive trains and triple extrastimuli was performed for induction of VT. When a 12-lead ECG of spontaneous VT was available, clinical VT was defined by match in all 12 leads. In absence of 12-lead ECG of the spontaneous VT, clinical VT was defined as the one matching the morphology and cycle length within 30 ms of the ICD stored electrograms from spontaneous VT episodes. Every spontaneously occurring VT was considered clinical. The remaining VTs induced by PES were defined as nonclinical and routinely targeted by the ablation. Areas of late activation or local conduction delay as evidence by split, fractionation or isolated late potentials were identified and targeted for ablation.

Supplementary results

Analysis of patients without prior procedures

Among ES patients without prior procedures, nc-VT patients a VT free survival not significantly different from no-VT patients (72.4% vs 72.7%, long-rank p=0.58); both classes had a better VT free survival compared c-VT (30.4%, long-rank p<0.001 and long-rank p<0.001, respectively) (Supplementary Figure 1).

When considering only patients without prior procedures among those with ES, no-VT patients had a better survival compared to nc-VT, c-VT ones (86.0% vs 73.6% and 52.2%, long-rank p=0.005 and p<0.001); nc-VT patients had an higher survival compared to c-VT ones (long-rank p<0.028) (Supplementary Figure 3).

Transplant-free survival

Among the study population, 53 patients underwent OHT; the rate of transplant did not differ between patients with or without ES (4.3% vs 1.9% long-rank p= 0.385).

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Supplementary Figures and Legends

Supplementary Figure 1. Kaplan-Meier curves of survival free from VT recurrences among patients with absence of any VT inducible (A), at least one VT morphology still inducible (B), only non-clinical VT still inducible (C), clinical VT still inducible after ablation (D), by presence or absence of Electrical Storm.

Supplementary Figure 2. Kaplan-Meier curves of survival in patients with no VT inducible (A), at least one VT of any type still inducible (B), only non-clinical VT still inducible (C), clinical VT still inducible at PES after the ablation (D) by presence or absence of Electrical Storm by Kaplan-Meier curves.

Supplementary Figure 3. Survival free from VT recurrences among patients with ES by the result of PES after the first VT ablation

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Supplementary Figure 4. Complete initial Cox proportional hazard modeling for VT recurrences in patients with Electrical Storm

The figure shows the results of the complete initial Cox model for VT recurrences in the group of patients with ES, including gender, age, type of cardiomyopathy, result of PES after the ablation, Left Ventricular Ejection Fraction (LVEF), New York Heart Association Functional Classification (NYHA class), hypertension (HTN), hyperlipidemia, atrial fibrillation (AF), diabetes mellitus (DM), chronic kidney disease (CKD), occurrence of previous VT ablations (Previous Abl), interaction between LVEF and PES (delta LVEF), interaction between preious ablation and PES (delta Abl) were included in the model as covariates.

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Supplementary Figure 5. Survival free from death among patients with ES by the result of PES after the first VT ablation

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Supplementary Figure 6. Complete initial Cox proportional hazard modeling for death in patients with Electrical Storm

The figure shows the results of the complete initial Cox model for Death in the group of patients with ES, including gender, age, type of cardiomyopathy, result of PES after the ablation, Left Ventricular Ejection Fraction (LVEF), New York Heart Association Functional Classification (NYHA class), hypertension (HTN), hyperlipidemia, atrial fibrillation (AF), diabetes mellitus (DM), chronic kidney disease (CKD), interaction between LVEF and PES (delta LVEF), interaction between preious ablation and PES (delta Abl) , PES and previous ablation)occurrence of previous VT ablations (Previous Abl), were included in the model as covariates.

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