Catheter Ablation of Ventricular Tachycardia and Mortality in Patients with. Nonischemic Dilated Cardiomyopathy: Can Noninducibility after Ablation be

Transcription

1 Catheter Ablation of Ventricular Tachycardia and Mortality in Patients with Nonischemic Dilated Cardiomyopathy: Can Noninducibility after Ablation be a Predictor for Reduced Mortality? Running title: Dinov et al.; VT ablation and mortality in nonischemic DCM Borislav Dinov, MD; Arash Arya, MD; Alexandra Schratter, MD; Valentina Schirripa, MD; Lukas Fiedler, MD; Philipp Sommer, MD; Andreas Bollmann, PhD; Sascha Rolf, MD; Christopher Piorkowski, MD; Gerhard Hindricks, MD Department of Cardiac Electrophysiology, y, Heart Center, University of Leipzig, Leipzig, Germany Correspondence: resp onde nce: Borislav Dinov, MD University of Leipzig Heart Center Department of Electrophysiology Struempellstrasse Leipzig Germany Tel: Fax: dinov@gmx.de Journal Subject Code: [22] Ablation/ICD/surgery 1

2 Abstract: Background - Data on outcomes after catheter ablation (CA) of ventricular tachycardia (VT) in nonischemic dilated cardiomyopathy (NIDCM) patients are insufficient. We aimed to investigate the effects of successful CA of VT on cardiac mortality in patients with NIDCM. Methods and Results patients with NIDCM (86 males, mean age 58.8 ± 15.2 years, mean ejection fraction 33.3 ± 11.9 %) underwent VT ablation. After CA a programmed ventricular stimulation to test for success was performed. Complete VT noninducibility was achieved in 62 (61%) patients, and partial success or failure in 32 (31%) patients. During 2-years of follow-up, VT recurrence was observed in 33 patients (53%) without inducible VTs and in 24 patients (75%) with inducible VT inducible (P=0.041). VT inducibility was associated with higher VT recurrence (adjusted HR=1.84; 95% CI ; P=0.025). The primary endpoint of all-cause mortality was reached in 9 patients (15%) with non-inducible VTs vs. 11 patients (34%) with inducible sustained VTs (P=0.026). VT inducibility was associated with all-cause mortality (adjusted HR=2.73; 95% CI ; P=0.049). Conclusions - In patients with NIDCM and recurrent sustained VTs a complete ablation of all inducible VTs may be achieved in 60% of the cases. The complete noninducibility nduc ibili ity may be a preferable endpoint of ablation because it was associated with better ter long-term success. Importantly, tly, if possible to achieve through ablation, a complete VT noninducibility nind nduc ibil ilit ity was associated at with reduction of the likelihood l ihood for all-cause mortality l in patients t with NIDCM. Key words: ablation, ventricular tachycardia, dilated cardiomyopathy, mortality 2

3 The field of catheter ablation (CA) of ventricular tachycardia (VT) is currently expanding, driven by the advent of new technologies, the growing expertise in this area, and the increasing number of patients with implantable cardioverter-defibrillator (ICD) therapies. In the last decade, there have been an increasing number of studies evaluating different ablation strategies and outcomes after CA of VT in patients with coronary artery disease 1-6. However, data on nonischemic dilated cardiomyopathy (NIDCM) patients are insufficient. In particular, a few publications have suggested rather disappointing long-term outcomes after VT ablation in NIDCM. 7-9 Another recent study failed to prove any survival benefits after catheter ablation of VT in nonischemic heart disease. 10 The reported difference in post-ablation outcomes between ischemic and nonischemic VTs may be related to certain peculiarities in underlying arrhythmia substrate in NIDCM, such as less late potentials, involvement of epimyocardial layers, absence of dense scar etc. 8,11-13 The aim of the present study was to investigate the effect of VT noninducibility as an endpoint and proof for successful sful ablation on the rate of VT recurrence e and survival i in NIDCM patients. ts. Methods Study Population In this observational, single-center study, we enrolled patients with sustained VT and NIDCM who underwent CA at the Heart Center of Leipzig between January 2008 and June Patients with previous VT ablation procedures were not included in the study. In the study were included patients who fulfilled the criteria for dilated cardiomyopathy recommended from the recent guidelines. 14 Ischemic heart disease was previously excluded with coronary angiography. 3

4 Medical files were carefully reviewed to identify the possible cause of the underlying dilated cardiomyopathy. Patients without any identifiable cause were classified as having idiopathic NIDCM, and the rest as secondary NIDCM. Electrophysiological Study Before the CA procedure, all patients signed an informed consent for undergoing the procedure and for the use of their clinical data for study purposes. The study was approved by the Institutional review committee. The patients were prepared according to the clinical routine at our institution. The procedure was performed under conscious sedation. The primary mapping approach was endocardial in all cases. After a single transseptal puncture, a steerable sheath (Agilis TM, St. Jude Medical) was used to introduce the ablation catheter. All patients were administered heparin intravenously.. If an epicardial al VT was suspected, spec based on ECG morphology, lack of endocardial low voltage areas, or incongruous n endocardial activation map, a subxiphoid puncture was performed. rmed. In patients without ongoing g VT, a programmed ventricular stimulation (PVS) was performed to test for VT inducibility. ibility. Signals were recorded rded using a multi-channel nel recording rdin system (Prucka CardioLab, GE Healthcare, Waukesha, Wis, USA). The PVS protocol included stimulation from the right ventricular apex and outflow tract with four different basic cycle lengths (500, 430, 370, 330 ms) and introduction of up to 3 extrastimuli until the ventricular effective refractory period or coupling interval of 200 ms was reached. If the VT was still not inducible additional stimulation in the left ventricle was performed. The same induction protocol was used to re-induce the VT after CA. Electro-anatomical Mapping and Catheter Ablation Endocardial left ventricular mapping was performed using electro-anatomical 3D-mapping 4

5 systems (Carto-3 or Carto-RMT, Biosense Webster Inc., CA, USA or EnSite, St. Jude Medical Inc). Electroanatomical voltage mapping was used to delineate the underlying substrate. Local bipolar electrograms, demonstrating peak-to-peak amplitude ere defined as healthy, and low-amplitude electrograms <0.5 mv were defined as dense scar. In cases of normal LV electrograms, right ventricular (RV) or epicardial mapping were additionally performed. All fragmented and late potentials were annotated on the map. In patients with ongoing or hemodynamically stable VTs activation and entrainment mapping were performed to localize the exit sites and critical isthmuses of VT. Activation mapping was also performed in cases of frequent uniform premature ventricular beats (PVB). Open-irrigated tip ablation catheters were used to perform radiofrequency ablation. atio Power settings of up to 50 W and irrigation rates of up to 30 ml/min (Navistar Thermocool or Navistar Thermocool-RMT oo Biosense s Webster er Inc) or power settings of up to 50 W and irrigation riga rates of up to 17 ml/min (Coolflex catheter, St. Jude Medical Inc) were used. During the CA, PVS was performed to re-induce the VTs. Because of the uncertainty nty to define the clinical VT we adopted the complete noninducibility ninduc ibility as an endpoint nt and proof of for success of the ablation procedure. For that reason, patients were divided into 2 groups depending on the inducibility: group 1) complete success defined as noninducibility of any VT, and group 2) partial success or failure defined as persistent inducibility of sustained VT after CA. 15 Patient Follow-up After discharge, all patients were followed up at scheduled outpatient visits every three months or earlier in the case of ICD shock therapies. The follow-up was limited to 2 years. Data on VT recurrences and device therapies were collected through device interrogation at these regular visits. Mortality data were confirmed via telephone contact with the referring cardiologists or 5

6 primary care physicians. The primary endpoint of the study was all-cause mortality. The recurrence of sustained VT requiring ICD therapy was defined as secondary endpoint. Statistical Analysis Continuous variables with normal distribution are reported as mean ± standard deviation, whereas categorical variables are reported as absolute numbers and proportions. Student t-test, chi-square test and Fisher s exact test were used to compare differences across groups. Survival free from VT recurrence during the follow-up period was estimated by the Kaplan-Meier method, and log-rank statistics were used to compare different groups. Multivariaable Cox regression analysis using the method of forced entry in which all variables were forced into the model simultaneously was used to identify correlates e of VT recurrence and all-cause mortality. In the mode.. All tests s were two-sided and p-values < were considered ed statistically significant. The statistical analysis was performed rmed using SPSS S 17.0 (IBM, Armonk, NY, USA). Results Baseline Clinical Characteristics One hundred and two consecutive patients (86 male; mean age of 58.8 ± 15.2 years; mean EF of 33.3 ± 11.9%) with primary and secondary NIDCM and sustained VTs were included in the study. Thirty five patients (34%) were referred for ablation because of electrical storms; fifty seven patients (56%) had at least 1 ICD shock in the preceding 6 months; and twelve patients (12%) presented with an incessant VT. Fifty five patients (54%) were on anti-arrhythmic drugs (AAD) at the time of admission. Fifty nine (58%) patients had secondary NIDCM, and the cause 6

7 remained unclear in the rest 43 (42%). The causes of NIDCM, as well as the other baseline clinical characteristics and co-morbidities are presented in table 1. Baseline Procedural Characteristics and Ventricular Tachycardia Inducibility before Ablation Endocardial electro-anatomical mapping (voltage, activation or both) was the primary mapping approach and was performed in all 102 patients. Voltage mapping was performed in 87 patients. Low voltage ( mv) endocardial areas were observed in 48 (46%) patients; both endocardial and epicardial low voltage areas ( mv) in 25 (24%) patients. In 17 (16%) patients low voltage areas ( mv) were observed only on the epicardial LV surface. The mean endocardial bipolar voltage area ( mv) was 34.6 ± 36.2 cm 2 and the mean epicardial bipolar voltage area ( mv) was 58 ± 58.4 cm 2. The mean unipolar voltage area (< 8.3 mv) endocardially was 118 ± 73 cm 2. In 15 (14%) patients t only activation tion mapping p of ongoing VT or presumed ed PVB as triggers gers of VT was performed. Ventricular r tachycardia was ongoing at the start of the procedure in 12 patients (12%); was inducible with PVS in 73 patients ts (72%); and remained ed non-inducible nduc ible in 13 patients ts (13%). PVS at the beginning of the procedure was not performed in four (4%) cases and ongoing VTs or frequent PVB were targeted instead. A mean of 2.1 ± 1.3 VTs/patient were inducible. The baseline procedural characteristics are presented in table 2. Acute Outcomes and Procedure-related Complications Based on the inducibility after ablation, a complete success was observed in 62 (61 %) patients; partial success or failure was observed in 32 (31 %) patients. PVS after ablation was not performed in 8 (8%) cases due to the fact that only the ongoing VT and PVB were targeted in 7 patients, and because pericardial tamponade occurred in one case. Overall 9 (9%) patients 7

8 experienced postprocedural complications. (Table 2) Causes of Death All patients except two died from cardiac arrest, worsening of heart failure or combination of both so that cardiac mortality contributed almost entirely to the mortality in this cohort of patients without coronary artery disease. One patient died from tension pneumomediastinum as a consequence of surgical drainage of pericardial tamponade after CRT implantation, and another one from unrecognized hypoglycemia (Table 3). Effects of Postablation Noninducibility on the VT recurrence and Correlates for VT Recurrence Because of the omitted PVS after CA in 8 patients they were excluded from the analysis of the VT recurrence and mortality, given the uncertainty ty in classifying them as success or failure. The baseline clinical cal and procedural characteristics cter tics of the remaining i 94 patients t with inducible ible and non-inducible n-in VTs are presented in table 4. In comparison on to the patients with non-inducible n-in VTs, the patients with persistent VT inducibility ility had more VTs/patient: 2.84 ± 1.46 vs ± 1.1; 1; P=0.0001; 001; longer procedure duration: 142 ± 66.9 vs. 105 ± 73 min; P=0.001; 01; and required red more frequently epicardial ablation: 44% vs. 21%; P= Notably, patients with persistently inducible VTs had more procedure-related complications as compared to patients with complete VT noninducibility: 2 (3%) vs. 5 (16%); P=0.043 In 94 patients, after 2-years of follow-up, VT recurrence was observed in 33 patients (53%) with complete success (no VT inducible) and in 24 patients (75%) with partial procedural success or failure (VT inducible) (P=0.041). In a univariable analysis, the probability of VTrecurrence was significantly higher in the group with inducible VTs as compared to the group without inducible VTs (HR=2.01; 95%CI ; p=0.01)(figure1). After adjustments for the 8

9 baseline differences and relevant clinical confounders, such as age, LV ejection fraction, NYHA class, number of VTs/patient, epicardial ablation, egfr and use of AAD or beta-blockers, the persistent inducibility of VT at the end of the procedure and the egfr were the only significant correlates for VT-recurrence: HR for VT inducibility=1.84; 95% CI ; P=0.025 and HR for egfr=0.99; 95% CI ; P=0.021 (Table 5). Effects of Postablation VT Noninducibility on All-cause Mortality At the end of the 2-years follow-up period, the primary endpoint of all-cause mortality was reached in 9 patients (14%) with non-inducible VTs vs. 11 patients (34%) with inducible sustained VTs at the end of the procedure (P=0.026). In unadjusted analysis, the rate of all-cause death was significantly higher in patients with inducible VTs (HR=3.08; 95% CI ; 7.46 P=0.013) (Figure 2). After adjustments for the significant ificant clinical variables (age, atrial fibrillation, illation, chronic pulmonary disease, e, egfr, NYHA class, s, ejection fraction, and time to VT recurrence), r ence), the inducibility of any sustained VT at the end of the procedure re was significantly ificantly associated with all-causel-caus mortality (HR=2.73; 95% CI ; 0 P=0.049). Additionally, egfr (HR=0.96; 95% CI ;.99; 9; P=0.005) 05) and time to VT recurrence renc (HR=0.996; 95% CI ; P=0.049) were associated with an increased rate of all-cause death (Table 6). Effects of Pre- and Postablation VT Noninducibility on VT recurrence and All-Cause Mortality VT recurrence was observed in 8 (62%) out of 13 patients with noninducible VTs at the beginning of the procedure vs. 26 (51%) out of 51 patients rendered non inducible at the end of the ablation (P=0.548). Regarding the all-cause mortality, death occurred in 3 (23%) out of 13 primary non-inducible patients vs. 7 (14%) out of 51 patients rendered non inducible after ablation (P=0.411). 9

10 Discussion Programmed ventricular stimulation is a widely accepted tool to test for acute procedural success after catheter ablation of VT Previous studies have shown that VT noninducibility after CA was associated with improved VT-free survival and reduced mortality in patients with coronary artery disease. 2,5,18 In contrast, the influence of post-procedural VT inducibility as a proof of acute success on the outcomes in patients with NIDCM is controversial and based on data from several studies with a limited number of patients. 10,19 Endpoints Definition and Acute Outcomes after Ablation Having in mind the uncertainties in the classification of a VT as a clinical one, as well as some recently published data, we adopted the complete noninducibility of any sustained monomorphic morp VT as an endpoint and a proof of acute success after CA. 19 Using this definition, ition, the achieved study which comparable previously published data. 9,10 acute success rate in our was 60% is able to a. VT Noninducibility after CA and VT recurrence In patients with NIDCM it was previously demonstrated ted that inducibility ibility of ventricular tachycardia ardi a or fibrillation ion was associated soci ated with an increased ed likelihood ihoo of subsequent sequ ent ICD therapies in addition to the LV ejection fraction. 20 In line with this finding, we proved a decreased likelihood of VT recurrence in patients with NIDCM and complete VT noninducibility in comparison to patients with partial success or failure after catheter ablation. Previously, Piers et al reached the same conclusion and suggested that noninducibility may be an appropriate endpoint in patients with NIDCM. 19 In contrast with our results and the data from the above mentioned studies, Tokuda et al. could not prove any association between the post-ablation inducibility and the VT recurrence in a cohort of patients with miscellaneous non-ischemic cardiomyopathies including hypertrophic cardiomyopathy. 10 These contradictory results can be 10

11 explained by non-reentrant arrhythmia mechanisms operative in some cardiomyopathies, as well as by differences between the PVS protocols and endpoint definitions. VT Noninducibility after CA and Mortality In this study we proved for the first time that, if possible to achieve with CA, the complete VT noninducibility was associated with survival benefit in patients with NIDCM. The persistent VT inducibility was associated with an increased likelihood for death. Since in our study most of the patients with NIDCM treated by CA died due to cardiac arrest, worsening heart failure, or a combination of both, a successful CA may have improved the survival chances of these patients, provided a complete noninducibility would have been achieved. At the same time, patients with partially successful ablation or failure experienced less procedure-related complications cati ons as compared to those with completely successful procedure. Therefore, the risks of VT recurrences should be weighted ed carefully ly against the risks of a prolonged onge CA. In addition i to noninducibility, the time to first VT recurrence was associated sociated with increased mortality. The unfavorable prognosis of patients with earlierer VT recurrence ence may indicate more advanced stage of ventricular remodeling and hence poorer survival or may be the immediate iate cause of death in some cases. s. Furthermore, other factors such as the reduction of the VT burden may possibly play a role for the decline of the mortality after successful ablation. On the other hand, an impossibility to achieve a complete acute success may be considered as an indirect evidence of extensive and severe LV scar involvement which by its very nature is associated with VT recurrences, loss of contractile function, and as a consequence, with a higher mortality. This hypothesis is supported by a recent study in NIDCM patients showing that the scar transmurality in LGE - MRI images of the LV was associated with VT inducibility with PVS.21 11

12 Implications for the Clinical Practice and Future Studies Our results suggest that, where possible, a modification of the existing substrate to achieve a complete VT noninducibility should be attempted because it may reduce the likelihood of VT recurrence and further deterioration of heart failure in patients with NIDCM. Moreover, the impossibility to achieve a complete elimination of all inducible VTs was associated with increased probability of cardiac and all-cause mortality. This association may be explained with insufficient ablation or severe LV impairment as a consequence of extensive scarring. Further studies are needed to explore the impact of the arrhythmogenic substrate on the mortality in NIDCM patients. Study Limitations Our study was a prospective, observational, single-center nter study. The presented e results are from an experienced ed center and patients ts with prior unsuccessful sful ablation atio were excluded; d; therefore these data may be not valid for the general population. Another major limitation tion of defining noninducibility ibility as "ablation success" c ss" is that in some cases VT remained noninducible ninduc at the beginning ing of the procedure. re. However, the noninducibility before CA was not significantly ntly different between patients with complete procedural success and partial procedural success or failure. Moreover, patients with noninducible VTs at the start that remained non inducible throughout the entire procedure had similar VT recurrence and mortality outcomes to those that were inducible at the beginning and rendered non inducible after ablation. The possibility that these patients would have done better if ablation was stopped at an earlier endpoint cannot be excluded. Another limitation is that non-reentrant mechanisms may influence the inducibility with PVS, although re-entry is expected to be the prevailing arrhythmia mechanism in scarrelated VTs. Epicardial mapping and ablation was performed only in the half of the patients with 12

13 persistently inducible VTs, which may possibly influence the acute and long-term outcomes. Conclusions In patients with NIDCM and recurrent sustained VTs a complete ablation of all inducible VTs may be achieved in 60% of the cases. The complete noninducibility may be a preferable endpoint of ablation because it was associated with better long-term success. Importantly, if possible to achieve through ablation, a complete VT noninducibility was associated with reduction of the likelihood for cardiac and all-cause mortality in patients with NIDCM. Acknowledgments: We thank Dr. Hedi Razavi for her invaluable help in the revision of the manuscript. Conflict of Interest Disclosures: Borislav Dinov, Arash Arya, Alexandra Schratter, Valentina a Schirripa, Lukas Fiedler, Andreas Bollmann, Sascha Rolf, Christopher Piorkowski, owski, and Gerhardrd Hindricks have no conflict of interest to declare. e References: es: 1. Marchlinski FE, Callans DJ, Gottlieb CD, Zado E. Linear ablation leasions for control of unmappable ventricular tachycardia in patients with ischemic and nonischemic cardiomyopaty. Circulation. 2000;101: Della Bella P, Ponti R, Uriarte JR, Tondo C, Klercy C, Carbucicchio C, Storti C, Riva S, Longobardi M. Catheter ablation and antiarrhythmic drugs for haemodinamically tolerated postinfarction ventricular tachycardia. Long-term outcome in relation to acute electrophysiological findings. Eur Heart J. 2002;23: Reddy VY, Reynolds MR, Neuzil P, Richardson AW, Taborsky M, Jongnaransin K, Sediva L, Ruskin JN, Josephson ME. Prophylactic catheter ablation for the prevention of defibrillator therapy. N Engl J Med. 2007;357: Stevenson W, Wilber D, Natale A, Jackman WM, Marchlinski FE, Talbert T, Gonzales MD, Worley SJ, Daoud EG, Hwang C, Schuger C, Bump TE, Jazayeri M, Tomassoni GF, Kopelman HA, Soejima K, Nakagawa H. Multicenter Thermocool VT Trial Investigators. Irrigated radiofrequency catheter ablation guided by electroanatomical mapping for recurrent ventricular 13

14 tachycardia after myocardial infarction: the multicenter thermocool ventricular tachycardia ablation trial. Circulation. 2008;118: Carbucicchio C, Santamaria M, Trevisi N, Maccabelli G, Giraldi F, Fassini G, Riva S, Moltrasio M, Cireddu M, Veglia F, Della Bella P. Catheter ablation for the treatment of electrical storm in patients with implantable cardioverter-defibrillators: short- and long-term outcomes in a prospective single-center study. Circulation. 2008;117: Kuck KH, Schaumann A, Eckardt L, Willems S, Ventura R, Delacretaz E, Pitschner HF, Kautzner J, Schumacher B, Hansen P. Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary heart disease (VTACH): a multicentre randomised controlled trial. Lancet. 2010;375: Kottkamp H, Hindricks G, Chen X, Brunn J, Willems S, Haverkamp W, Block M, Breithardt G, Borggrefe M. Radiofrequency catheter ablation of sustained ventricular tachycardia in idiopathic dilated cardiomyopathy. Circulation. 1995; 92: Dinov B, Fiedler L, Schönbauer R, Bollmann A, Rolf S, Piorkowski ki C, Hindricks G, Arya A. Outcomes in catheter cblation of ventricular tachycardia in dilated noniischemic cardiomyopathy opathy in comparison to ischemic cardiomyopathy: athy: Results from the prospective HEart Centre of LeiPzig VT (HELP-VT) Study. Circulation. 2014;129: Soejima K, Stevenson WG, Sapp JL, Selwyn AP, Couper G, Epstein LM. Endocardial and epicardial radiofrequency ablation of ventricular tachycardia associated with dilated cardiomyopathy: the importance of low voltage scars. J Am Coll Cardiol. 2004;10: Tokuda M, Tedrow UB, Kojodjojo j P, Inada K, Koplan BA, Michaud GF, John RM, Epstein LM, Stevenson enso WG. Catheter er ablation of ventricular tachycardia ardi in non-ischemic ic heart disease. Circ Arrhythm Electrophysiol. ol. 2012;5: ;5: Cano O, Hutchinson M, Lin D, Garcia F, Zado E, Bala R, Riley M, Cooper J, Dixit S, Gerstenfeld E, Callans D, Marchlinski FE. Electroanatomic substrate and ablation outcome for suspected epicardial ventricular tachycardia in left ventricular nonischemic cardiomyopathy. J Am Coll Cardiol. 2009;54: Hsia HH, Callans DJ, Marchlinski FE. Characterization of endocardial electrophysiological substrate in patients with nonischemic cardiomyopathy and monomorphic ventricular tachycardia. Circulation. 2003;108: Nakahara S, Tung R, Ramirez R, Michowitz Y, Vaseghi M, Buch E, Gima J, Wiener I, Mahajan A, Boyle NG, Shivkumar K. Characterization of the arrhythmogenic substrate in ischemic and non-ischemic cardiomyopathy: implications for catheter ablation of hemodynamically unstable ventricular tachycardia. J Am Coll Cardiol. 2010;55: Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, Dubourg O, Khul U, Maisch B, McKenna WJ, Monserrat L, Oankuweit S, Rapezzi C, Seferovic P, Tavazzi L, Keren 14

15 A. Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group Myocardial and Pericardial Diseases. Eur Heart J. 2008; 29: Aliot EM, Stevenson WG, Almendral-Garrote JM, Bogun F, Calkins H, Delacretaz E, Della Bella P, Hindricks G, Jais P, Josephson M, Kautzner J, Kay N, Kuck KH, Lerman B, Marchlinski F, Reddy V, Schalij MJ, Schlilling R, Soejima K, Wilber D. EHRA/HRS Expert Consensus on Catheter Ablation of Ventricular Arrhythmias. Hearth Rhythm. 2009;6: Brugada P, Green M, Abdollah H, Wellens H. Significance of ventricular arrhythmias initiated by programmed ventricular stimulation: The importance of the type of ventricular arrhythmia induced and the number of premature stimuli required. Circulation. 1984;69: Morady F, Di Carlo L, Winston S, Davis J, Scheinmann M. A prospective comparison of triple extrastimuli and left ventricular stimulation in studies of ventricular tachycardia induction. Circulation.1984;70: Frankel DS, Mountantonakis SE, Zado ES, Anter E, Bala R, Cooper J, Deo R, Dixit S, Epstein AE, Garcia FC, Gerstenfels EP, Hutchinson MD, Lin D, Patel V, Riley MP, Robinson MR, Tzou WS, Verdino RJ, Callans DJ, Marchlinski FE. Noninvasive programmed ventricular r stimulation early after ventricular tachycardia ablation to predict risk of late recurrence. J Am Coll Cardiol. 2012;59: Piers SR, Leong DP, van Huls van Taxis CF, Tayyebi yebi M, Trines SA, Pijnapples DA, Delgado V, Schalij MJ. Outcome of ventricular tachycardia ardi ablation in patients ts with nonischemic nisc cardiomyopathy: opat the impact of noninducibility. ninduc ibility Circ Arrhythm Electrophysiol. ol. 2013;6: Gatzoulis K, Vouliotis otis A, Tsiachris D, Salourou M, Archontakis S, Dilaveris is P, Gialernios T, Arsenos P, Karystinos G, Sideris S, Kallikazaros I, Stefanadis C. Primary prevention of sudden cardiac death in a nonischemic dilated cardiomyopathy population. Reappraisal of the role of programmed ventricular stimulation. Circ Arrhythm Electrophysiol. 2013;6: Nazarian S, Bluemke DA, Lardo AC, Zviman MM, Watkins SP, Dickfeld TL, Meininger GR, Roguin A, Calkins H, Tomaselli GF, Weiss RG, Berger RD, Lima JA, Halperin HR. Magnetic resonance assessment of the substrate for inducible ventricular tachycardia in nonischemic Cardiomyopathy. Circulation. 2005;112:

16 Table 1: Baseline clinical characteristics Baseline clinical characteristics N (102) Age, y 58.8 ± 15.2 Gender, male n (%) 86 (84) NIDCM Cause Idiopathic 43 (42) Post-myocarditis 21 (21) Hypertension/LV Hyperthrophy 12 (12) Systemic sclerosis 1 (1) Alcoholic cardiomyopathy 5 (5) Primary mitral regurgitation 8 (8) Aortic regurgitation 6 (6) Sarcoidosis 1(1) Idiopathic LV aneurysm 2 (2) Grave s disease 1 (1) Rheumatoid arthritis 1 (1) Familial/SCN5A homoz. 1 (1) Co-morbidities itie ies Arterial hypertension, n, n (%) 53 (52) Diabetes mellitus, litus, n (%) 26 (26) Chronic pulmonary disease, e, n (%) 13 (13) Peripheral eral vascular disease, e, n (%) 3 (3) Cerebral vascular disease, e, n (%) 5 (5) Heart failure NYHA > II, I, n (%) 41 (40) Atrial fibrillation/flutter, ion/ flut ter, n (%) 38 (37) LV Ejection fraction, % 33.3 ± 11.9 LV EDV, ml 199 ± 78 ICD-shocks, n (%) 57 (56) Electrical storm, n (%) 35 (34) Incessant VT, n (%) 12 (12) AAD at admission, n (%) 55 (54) ICD at discharge, n (%) 100 (98) CRT-D, n (%) 45 (44) AAD at discharge, n (%) 49 (48) Beta-blockers at discharge, n (%) 90 (88) All data are presented as mean values ± SD or numbers and percentages. NIDCM = nonischemic dilated cardiomyopathy; LV = left ventricle; VT = ventricular tachycardia; EDV = end-diastolic volume; ICD = implantable cardioverter defibrillator; AAD=antiarrhythmic drugs; CRT-D = cardiac resynchronization therapy defibrillator 16

17 Table 2: Baseline procedural characteristics Baseline procedural characteristics N (102) Programmed ventricular stimulation (PVS) Inducible with PVS, n (%) 73 (72) Ongoing at start, n (%) 12 (12) Non-inducible with PVS at start, n (%) 13 (13) PVS not performed at beginning, n (%) 4 (4) Remote magnetic navigation, n (%) 7 (7) Number of VTs/patient 2.1 ± 1.3 Epicardial mapping, n (%) 36 (35) Epicardial ablation, n (%) 29 (28) Substrate, n (%) Low-voltage endo. 48 (46) Low-voltage endo- and epic. 25 (24) No low-voltage ltage endo.; low voltage epic 17 (16) Activation mapping ping only 15 (14) Bipolar low voltage endo. (<1.5 mv), cm ± 36.2 Bipolar low voltage endo. (<0.5 mv), cm ± 22.5 Bipolar low voltage epic. (<1.5 mv), cm ± 58.4 Unipolar voltage area endo. (< 8.3 mv), cm ± 72.8 Procedural time, min 172 ± 59 Fluoroscopic time, min 35.5 ± 20.4 Ablation outcomes, n (%) VT Inducible or PVS not performed 40 (10) VT inducible 32 (31) PVS not performed 8 (8) VT non-inducible 62 (61) Procedure-related complications 9 (9) All data are presented as mean values ± SD or numbers and percentages. PVS= programmed ventricular stimulation; VT = ventricular tachycardia; Endo = endocardial; Epic = epicardial 17

18 Table 3: Cause of Death Causes of death N (21) Cardiac death 19 (91%) In-hospital death 4 (19%) Cardiac arrest (VT/VF=5; asystole=1) 6 (29%) End-stage heart failure 13 (62%) Other non-cardiac causes 2 (10%) Tension pneumomediastinum 1 (5%) Hypoglycemic shock 1 (5%) 18

19 Table 4: Comparison of the clinical and procedural characteristics between patients with inducible and non-inducible VT s after ablation Baseline clinical characteristics VT non-inducible (N 62) VT Inducible (N 32) P Value Age, y 59 ± ± Gender, male n (%) 50 (81) 29 (91) Idiopathic NIDCM, n (%) 38 (61) 19 (59) egfr, ml/min/1.73 m ± ± Peripheral vascular disease, n (%) 1 (2) 1 (3) 1.0 Chronic pulmonary disease, n (%) 6 (10) 5 (16) Arterial hypertension, n (%) 32 (52) 16 (50) Diabetes mellitus, n (%) 18 (29) 6 (19) Heart failure NYHA > II, n (%) 20 (32) 11 (34) Atrial fibrillation/flutter, n (%) 23 (37) 11 (38) LV Ejection fraction, % 34 ± ± LV EDV, ml 193 ± ± ICD-shocks, s, n (%) 31 (50) 22 (69) Electrical storm, n (%) 19 (31) 14 (44) Incessant VT, n (%) 8 (13) 5 (16) AAD at admission, n (%) 34 (55) 17 (53) Inducibility at beginning, n (%) Inducible or ongoing 50 (81) 31 (97) PVS not performed 2 (3) 0 (0.0) Non-inducible 10 (16) 1 (3) Remote magnetic navigation, n (%) 4 (7) 2 (6) Number of VTs/patient 1.79 ± ± Epicardial mapping, n (%) 18 (29) 15 (47) Epicardial ablation, n (%) 13 (21) 14 (44) Mapping, n (%) Low-voltage endo. 36 (58) 10 (31) Low-voltage endo. and epic. 12 (19) 12 (38)

20 No low-voltage endo.; low voltage epic 5 (8) 4 (13) Activation mapping 6 (10) 4 (13) Substrate, n (%) Bipolar voltage area endo (<1.5 mv), cm ± ± Bipolar voltage area endo (<0.5 mv), cm ± ± Bipolar voltage area epic, cm ± ± Unipolar voltage area endo, cm ± ± Procedural time, min 158 ± ± Fluoroscopic time, min 32.5 ± ± Procedure-related complications 2 (3) 5 (16) ICD at discharge, n (%) 60 (97) 32 (100) CRT-D, n (%) 28 (45) 14 (44) AAD at discharge, n (%) 25 (40) 19 (59) Beta-blockers at discharge, n (%) 53 (86) 29 (91) All data are presented as mean values ± SD or numbers and percentages. NIDCM = nonischemic dilated cardiomyopathy; egfr= estimated ted glomerular filtration rate; LV = left ventricular; EDV = end-diastolic dias volume; VT = ventricular tachycardia; ICD = implantable cardioverter r defibrillator; AAD = antiarrhythmic arrhythmic drugs; CRT-D = cardiac resynchronization ronization therapy defibrillator. r. 20

21 Table 5: Univariable and Multivariable Analysis for the Ventricular Tachycardia Recurrence Clinical variables Univariable Multivariable HR 95%CI P HR 95%CI P Partial success or failure Age, year Heart Failure > NYHA II LV EF% Number VTs/patient Epicardial ablation AAD at discharge egfr egfr= estimated glomerular filtration ion rate; LV = left ventricular; VT = ventricular tachycardia; ardi a; AAD = antiarrhythmic drugs; EF = ejection fraction 21

22 Table 6: Univariable and Multivariable Analysis for the All-cause Mortality Clinical variables Univariable Multivariable HR 95%CI P HR 95%CI P Partial success or failure Age, year Arterial hypertension Atrial fibrillation Chronic pulmonary disease egfr, ml/min Diabetes mellitus Heart Failure > NYHA II LV EF% Electrical storm Number VTs/patient Epicardial al ablation atio AAD at discharge Beta-blockers at discharge Time to VT Recurrence, days egfr= estimated glomerular filtration rate; LV = left ventricular; VT = ventricular tachycardia; AAD = antiarrhythmic drugs; EF = ejection fraction 22

23 Figure Legends: Figure 1: Effect of VT inducibility after ablation on VT recurrence. Kaplan-Meier curves, showing analysis of the freedom from ventricular tachycardia (VT) recurrence. The green line presents the arm with non-inducible VT s and the blue line presents the arm with inducible VTs. Figure 2: Effect of VT inducibility after ablation on all-cause mortality. Kaplan-Meier curves, showing the analysis of the all-cause mortality. The green line presents the arm with noninducible VT at the end of the procedure and the blue line presents the arm with inducible VTs. 23

24

25

26 Catheter Ablation of Ventricular Tachycardia and Mortality in Patients with Nonischemic Dilated Cardiomyopathy: Can Noninducibility after Ablation be a Predictor for Reduced Mortality? Borislav Dinov, Arash Arya, Alexandra Schratter, Valentina Schirripa, Lukas Fiedler, Philipp Sommer, Andreas Bollmann, Sascha Rolf, Christopher Piorkowski and Gerhard Hindricks Circ Arrhythm Electrophysiol. published online April 14, 2015; Circulation: Arrhythmia and Electrophysiology is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX Copyright 2015 American Heart Association, Inc. All rights reserved. Print ISSN: Online ISSN: The online version of this article, along with updated information and services, is located on the World Wide Web at: Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in Circulation: Arrhythmia and Electrophysiology can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office. Once the online version of the published article for which permission is being requested is located, click Request Permissions in the middle column of the Web page under Services. Further information about this process is available in the Permissions and Rights Question and Answerdocument. Reprints: Information about reprints can be found online at: Subscriptions: Information about subscribing to Circulation: Arrhythmia and Electrophysiology is online at: