TY - JOUR
AU - Zeppenfeld, Katja
AB - Abstract OBJECTIVES Surgical ventricular reconstruction (SVR) is an effective treatment to improve left ventricular (LV) function in patients with ischaemic heart failure and an LV anterior–apical aneurysm. Ventricular arrhythmia (VA) is an important cause for morbidity and mortality in these patients. Therefore, encircling cryoablation targeting the VA substrate may be required. Programmed electrical stimulation (PES) can identify patients at risk for VA. The objective of this study was to evaluate the incidence and type of VA during long-term follow-up after PES-guided encircling cryoablation concomitant to SVR for primary prevention of VA. METHODS Thirty-eight patients without spontaneous VA referred for SVR who underwent preoperative PES were included (PES group); 27 (71%) patients inducible for aneurysm-related VA received cryoablation. A historical cohort of 39 patients without spontaneous VA, preoperative PES and antiarrhythmic surgery served as the control group. Patients were discharged with an implantable cardioverter defibrillator (ICD). RESULTS During 74 ± 35 months of follow-up, no arrhythmic deaths occurred. Five-year survival for the total study population was 78%. Twenty-eight (36%) patients experienced ≥1 VA. There were no differences in the number and type of ICD therapies between groups: shocks, P = 0.699 and antitachypacing, P = 0.403. Five-year VA-free survival was 61% for the PES group and 65% for the control group (hazard ratio 1.67, P = 0.290). CONCLUSIONS The majority of the patients referred for SVR without previously documented VA was inducible for aneurysm-related VA. During the follow-up, more than one-third of the patients experienced sustained VA and 25% received appropriate ICD therapy. No difference in VA occurrence or ICD therapy was observed between groups. Ventricular arrhythmias , Ischaemic heart failure , Surgical ventricular reconstruction , Cryoablation INTRODUCTION Late sudden cardiac death due to ventricular arrhythmias (VAs) constitutes 30–50% of mortality in patients with ischaemic heart failure [1]. VA may be due to scar-related re-entry typically involving the scar borderzone, or due to heart failure-related mechanoelectrical changes, resulting in altered ion channel and transporter function [2–4]. Surgical ventricular reconstruction (SVR) is an effective treatment to reduce left ventricular (LV) volumes and improve LV function in patients with ischaemic heart failure and an LV anterior–apical aneurysm [5, 6]. Despite improved function and reduced wall stress, patients remain at risk for VA [2, 7, 8]. These VA can be due to re-entry in the scar borderzone which is left in place and is excluded by patch material during surgery [9]. Targeting aneurysm scar borderzone without additional mapping by an encircling cryoablation (EC) has been proven safe and effective for recurrent slow VA in these patients [10–12]. Programmed electrical stimulation (PES) can identify patients at risk for VA after myocardial infarction as it indicates the presence of an arrhythmogenic substrate [13, 14]. Patients who undergo SVR for an LV anterior–apical aneurysm without prior VA who are inducible for aneurysm-related re-entrant VA might benefit from substrate modification by concomitant EC of the scar borderzone, referred to as PES-guided EC, to prevent spontaneous VA. The objective of this study was to evaluate the incidence, type and timing of VAs after PES-guided EC concomitant to SVR for primary prevention of VA during long-term follow-up. METHODS Patient population This is a single-centre observational study. In 2007, PES-guided EC of the scar borderzone was added to the standard clinical protocol for patients without documented VA and accepted for SVR. The studied population consisted of 38 consecutive patients with ischaemic heart failure, an anterior–apical aneurysm, no history of VA and who underwent PES prior to elective SVR and PES-guided EC between 2007 and 2012 (PES group). Thirty-nine patients who underwent SVR without PES-guided EC with the same indication from 2003 onwards and with an implantable cardioverter defibrillator (ICD) at discharge served as the historical control group. This included a comprehensive preoperative evaluation with echocardiography and coronary angiography. The results were evaluated by a team of cardiologists and cardiothoracic surgeons. The Dutch Central Committee on Human-related Research allows the use of anonymous data without prior approval of an institutional review board, provided that the data are acquired for patient care. All data used for this study were acquired for clinical purposes and handled anonymously. Preoperative electrophysiological evaluation Before PES, antiarrhythmic drugs were discontinued for ≥5 half-lives. None of the patients used amiodarone at the time of PES. Two catheters were inserted through the right femoral vein, one placed at the His position and the second at the right ventricular apex and subsequently in the right ventricular outflow tract to perform PES. The PES protocol consisted of 3 drive cycle lengths (CLs; 600, 500 and 400 ms), with 1–3 ventricular extra stimuli (down to 200 ms or refractory period) and incremental burst pacing. An aneurysm-related VA substrate was assumed if PES induced a monomorphic VA, lasting >30 s or requiring termination because of haemodynamic compromise, was reinducible and the VA exit site was located at the aneurysm scar borderzone. The presumed exit site was determined based on the VA 12-lead electrocardiogram morphology [15]. All 12-lead VA electrocardiograms were analysed by 2 independent observers. In case of discrepancy, agreement was reached by consensus. Patients with aneurysm-related VA were candidates for EC concomitant to SVR. Patients without aneurysm-related VA underwent SVR only. Surgical technique Patients underwent SVR according to the previously described technique [6]. The operations were performed using cardiopulmonary bypass, aortic cross-clamping and intermittent warm blood cardioplegia. The LV was opened through the infarcted area. At the transitional zone between the viable and the scarred myocardium, EC was performed using a 4-mm diameter malleable cryoprobe (Cardioblate CryoFlex, Medtronic, Minneapolis, MN, USA) using argon gas. Overlapping linear applications, down to −150˚C for 90 s, were made to the aneurysm scar borderzone [9]. After EC, a Fontan stitch was placed at the transitional zone. The residual LV cavity was shaped and sized using a mannequin balloon at 55 ml/m2 body surface area (TRISVR, Chase Medical, Richardson, TX, USA), and the remaining defect was closed through an endoventricular Dacron patch plasty. Excluded fibrous scar tissue was sutured over the patch to improve haemostasis. Additional concomitant procedures were performed when indicated. After weaning the patient from extracorporeal circulation, transoesophageal echocardiography was repeated to assess the LV shape and function, patch integrity and valvular competency. Implantable cardioverter defibrillator settings In patients without an ICD before surgery one was implanted before discharge based on the preoperative left ventricular ejection fraction (LVEF) ≤30–35% according to the current European Society of Cardiology guidelines. Devices were programmed according to our standard institutional protocol for primary prevention: VA monitor zone (VACL 321–400 ms, no therapy), VA zone [VACL 261–320 ms, antitachycardia pacing (ATP) and if the VA continued ICD shocks] and VF zone (VACL ≤260 ms, ICD shocks). Settings were adapted when clinically indicated. Follow-up Patients were prospectively followed in an outpatient heart failure programme and maintained on optimal medical treatment for heart failure. ICDs were interrogated every 6 months. Printouts were reviewed for the occurrence of sustained VA, VACL and therapy mode. VAs were classified as sustained when lasting >30 s in the ICD monitor zone or when appropriate ICD therapy was initiated. Therapy was considered appropriate when occurring in response to any VA. Echocardiography was performed before discharge and afterwards annually. The follow-up started at the time of discharge and ended at the last outpatient clinic visit up to 2015 or death. Statistical analysis Continuous variables are expressed as mean ± standard deviation or median (interquartile range, IQR), and categorical variables are expressed as n (%), where appropriate. To compare the groups at baseline for continuous variables, the Student’s t-test (normally distributed data) and the Mann–Whitney U-test (non-normally distributed data) were used. For categorical data, the χ2 test or the Fisher’s exact test (n < 5 in any cell) was used. For analysis purposes, for each patient, the mean CL of all induced and/or spontaneous VAs was calculated. Intrapatient comparison for LVEF, New York Heart association (NYHA) class and VACL was performed using the paired-samples t-test or Wilcoxon paired test as appropriate. The incidence ratio was estimated for counted data. Overall survival and VA-free survival over time were analysed for the total study population by the Kaplan–Meier method. For calculating the follow-up time, a time-to-event approach was used, where patients were censored at the time of an event. To assess for differences and the effect of potential confounders on overall survival and VA-free survival between the groups, univariable and multivariable Cox regression models were constructed (Tables 4 and 5). Selection of potential confounders was based on clinical knowledge and comparing the baseline characteristics. To check for the robustness of the results, we performed a propensity score-adjusted analysis including the same confounders as included in the Cox model. All tests were 2-sided, and a P-value of <0.05 was considered statistically significant. Statistical analyses were performed using SPSS software (version 22, SPSS Inc., Chicago, IL, USA) and STATA version 14.1 XXX. RESULTS Patient characteristics Thirty-eight patients were included in the PES group and 39 patients in the control group. Baseline patient characteristics are listed in Table 1; both groups were similar, except for a worse NYHA class and lower ejection fraction in the control group. Patients were on optimal medical treatment for heart failure before undergoing SVR. Table 1: Baseline characteristics All (n = 77) PES group (n = 38) Control group (n = 39) P-value Male gender, n (%) 60 (78) 28 (74) 32 (82) 0.376a Age (years), mean ± SD 60 ± 10 63 ± 9 58 ± 11 0.051b Diabetes mellitus, n (%) 16 (21) 10 (26) 6 (15) 0.237a Atrial fibrillation, n (%) 8 (10) 6 (16) 2 (5) 0.125c MI-SVR duration (months), median (IQR) 36 (9–144) 48 (10–180) 28 (7–132) 0.133d NT-proBNP (pg/ml), median (IQR) 1358 (572–2151) 1346 (616–2253) 1369 (459–1885) 0.518d Primary reperfusion, n (%) 25 (32) 8 (21) 17 (44) 0.035a NYHA, n (%) <0.001b  Class 2 19 (25) 17 (45) 2 (5)  Class 3 53 (68) 21 (55) 32 (82)  Class 4 5 (6) 0 5 (13) EuroSCORE, median (IQR) 6 (4–14) 6 (4–14) 7 (4–18) 0.537d LVEF (%), mean ± SD 27 ± 8 29 ± 8 25 ± 7 0.015b LVESV index (ml/m2), mean ± SD 80 ± 45 81 ± 52 79 ± 39 0.880b LVEDV index (ml/m2), mean ± SD 111 ± 53 110 ± 63 112 ± 44 0.894b ACE-I/ARB, n (%) 74 (96) 37 (98) 37 (95) 0.571a Beta-blocker, n (%) 74 (96) 37 (98) 37 (95) 0.571a MRA, n (%) 46 (60) 26 (68) 20 (51) 0.125a All (n = 77) PES group (n = 38) Control group (n = 39) P-value Male gender, n (%) 60 (78) 28 (74) 32 (82) 0.376a Age (years), mean ± SD 60 ± 10 63 ± 9 58 ± 11 0.051b Diabetes mellitus, n (%) 16 (21) 10 (26) 6 (15) 0.237a Atrial fibrillation, n (%) 8 (10) 6 (16) 2 (5) 0.125c MI-SVR duration (months), median (IQR) 36 (9–144) 48 (10–180) 28 (7–132) 0.133d NT-proBNP (pg/ml), median (IQR) 1358 (572–2151) 1346 (616–2253) 1369 (459–1885) 0.518d Primary reperfusion, n (%) 25 (32) 8 (21) 17 (44) 0.035a NYHA, n (%) <0.001b  Class 2 19 (25) 17 (45) 2 (5)  Class 3 53 (68) 21 (55) 32 (82)  Class 4 5 (6) 0 5 (13) EuroSCORE, median (IQR) 6 (4–14) 6 (4–14) 7 (4–18) 0.537d LVEF (%), mean ± SD 27 ± 8 29 ± 8 25 ± 7 0.015b LVESV index (ml/m2), mean ± SD 80 ± 45 81 ± 52 79 ± 39 0.880b LVEDV index (ml/m2), mean ± SD 111 ± 53 110 ± 63 112 ± 44 0.894b ACE-I/ARB, n (%) 74 (96) 37 (98) 37 (95) 0.571a Beta-blocker, n (%) 74 (96) 37 (98) 37 (95) 0.571a MRA, n (%) 46 (60) 26 (68) 20 (51) 0.125a a χ2 test. b Student’s t-test. c Fisher’s exact test. d Mann–Whitney U-test. ACE-I: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor blocker; IQR: interquartile range; LVEF: left ventricular ejection fraction; LVEDV: left ventricular end-diastolic volume; LVESV: left ventricular end-systolic volume; MI: myocardial infarction; MRA: mineralocorticoid receptor antagonist; NT-proBNP: N-terminal pro-B-type natriuretic peptide; NYHA: New York Heart Association; PES: programmed electrical stimulation; SD: standard deviation; SVR: surgical ventricular reconstruction. Table 1: Baseline characteristics All (n = 77) PES group (n = 38) Control group (n = 39) P-value Male gender, n (%) 60 (78) 28 (74) 32 (82) 0.376a Age (years), mean ± SD 60 ± 10 63 ± 9 58 ± 11 0.051b Diabetes mellitus, n (%) 16 (21) 10 (26) 6 (15) 0.237a Atrial fibrillation, n (%) 8 (10) 6 (16) 2 (5) 0.125c MI-SVR duration (months), median (IQR) 36 (9–144) 48 (10–180) 28 (7–132) 0.133d NT-proBNP (pg/ml), median (IQR) 1358 (572–2151) 1346 (616–2253) 1369 (459–1885) 0.518d Primary reperfusion, n (%) 25 (32) 8 (21) 17 (44) 0.035a NYHA, n (%) <0.001b  Class 2 19 (25) 17 (45) 2 (5)  Class 3 53 (68) 21 (55) 32 (82)  Class 4 5 (6) 0 5 (13) EuroSCORE, median (IQR) 6 (4–14) 6 (4–14) 7 (4–18) 0.537d LVEF (%), mean ± SD 27 ± 8 29 ± 8 25 ± 7 0.015b LVESV index (ml/m2), mean ± SD 80 ± 45 81 ± 52 79 ± 39 0.880b LVEDV index (ml/m2), mean ± SD 111 ± 53 110 ± 63 112 ± 44 0.894b ACE-I/ARB, n (%) 74 (96) 37 (98) 37 (95) 0.571a Beta-blocker, n (%) 74 (96) 37 (98) 37 (95) 0.571a MRA, n (%) 46 (60) 26 (68) 20 (51) 0.125a All (n = 77) PES group (n = 38) Control group (n = 39) P-value Male gender, n (%) 60 (78) 28 (74) 32 (82) 0.376a Age (years), mean ± SD 60 ± 10 63 ± 9 58 ± 11 0.051b Diabetes mellitus, n (%) 16 (21) 10 (26) 6 (15) 0.237a Atrial fibrillation, n (%) 8 (10) 6 (16) 2 (5) 0.125c MI-SVR duration (months), median (IQR) 36 (9–144) 48 (10–180) 28 (7–132) 0.133d NT-proBNP (pg/ml), median (IQR) 1358 (572–2151) 1346 (616–2253) 1369 (459–1885) 0.518d Primary reperfusion, n (%) 25 (32) 8 (21) 17 (44) 0.035a NYHA, n (%) <0.001b  Class 2 19 (25) 17 (45) 2 (5)  Class 3 53 (68) 21 (55) 32 (82)  Class 4 5 (6) 0 5 (13) EuroSCORE, median (IQR) 6 (4–14) 6 (4–14) 7 (4–18) 0.537d LVEF (%), mean ± SD 27 ± 8 29 ± 8 25 ± 7 0.015b LVESV index (ml/m2), mean ± SD 80 ± 45 81 ± 52 79 ± 39 0.880b LVEDV index (ml/m2), mean ± SD 111 ± 53 110 ± 63 112 ± 44 0.894b ACE-I/ARB, n (%) 74 (96) 37 (98) 37 (95) 0.571a Beta-blocker, n (%) 74 (96) 37 (98) 37 (95) 0.571a MRA, n (%) 46 (60) 26 (68) 20 (51) 0.125a a χ2 test. b Student’s t-test. c Fisher’s exact test. d Mann–Whitney U-test. ACE-I: angiotensin-converting enzyme inhibitor; ARB: angiotensin receptor blocker; IQR: interquartile range; LVEF: left ventricular ejection fraction; LVEDV: left ventricular end-diastolic volume; LVESV: left ventricular end-systolic volume; MI: myocardial infarction; MRA: mineralocorticoid receptor antagonist; NT-proBNP: N-terminal pro-B-type natriuretic peptide; NYHA: New York Heart Association; PES: programmed electrical stimulation; SD: standard deviation; SVR: surgical ventricular reconstruction. Preoperative electrophysiological evaluation Of the 38 patients, 27 (71%) patients were inducible for 31 VAs, which were classified as aneurysm related, based on the 12-lead electrocardiogram. These had a VACL of 259 ± 54 ms, 24 VAs (77%) had a superior axis and 19 VAs (58%) had a left bundle branch block-type morphology; 17 VAs (55%) were haemodynamically not tolerated. Additional 3 VAs in 3 patients were non-aneurysm related; in 2 patients, 1 aneurysm-related and 1 non-aneurysm-related VAs were induced. In 1 patient, only a non-aneurysm-related VA was induced and was therefore not considered a candidate for concomitant EC. Surgical characteristics All patients underwent SVR. EC was applied at the aneurysm scar borderzone in all patients inducible for aneurysm-related VA. No statistical differences in surgical data were observed between groups (Table 2). Table 2: Surgical characteristics All (n = 77) PES group (n = 38) Control group (n = 39) P-value Coronary angiography bypass graft, n (%) 41 (53) 20 (53) 21 (54) 0.915a Mitral valve repair, n (%) 45 (58) 21 (55) 24 (62) 0.576a Tricuspid valve repair, n (%) 26 (34) 11 (29) 15 (38) 0.377a Aortic valve replacement, n (%) 4 (5) 2 (5) 2 (5) 0.979b Patch size (cm2), mean ± SD 14 ± 8 12 ± 5 16 ± 10 0.070c Cardiopulmonary bypass time (min), mean ± SD 204 ± 58 209 ± 52 194 ± 68 0.349c Aortic cross-clamp time (min), mean ± SD 141 ± 58 148 ± 41 129 ± 43 0.124c All (n = 77) PES group (n = 38) Control group (n = 39) P-value Coronary angiography bypass graft, n (%) 41 (53) 20 (53) 21 (54) 0.915a Mitral valve repair, n (%) 45 (58) 21 (55) 24 (62) 0.576a Tricuspid valve repair, n (%) 26 (34) 11 (29) 15 (38) 0.377a Aortic valve replacement, n (%) 4 (5) 2 (5) 2 (5) 0.979b Patch size (cm2), mean ± SD 14 ± 8 12 ± 5 16 ± 10 0.070c Cardiopulmonary bypass time (min), mean ± SD 204 ± 58 209 ± 52 194 ± 68 0.349c Aortic cross-clamp time (min), mean ± SD 141 ± 58 148 ± 41 129 ± 43 0.124c a χ2 test. b Fisher’s exact test. c Student’s t-test. PES: programmed electrical stimulation; SD: standard deviation. Table 2: Surgical characteristics All (n = 77) PES group (n = 38) Control group (n = 39) P-value Coronary angiography bypass graft, n (%) 41 (53) 20 (53) 21 (54) 0.915a Mitral valve repair, n (%) 45 (58) 21 (55) 24 (62) 0.576a Tricuspid valve repair, n (%) 26 (34) 11 (29) 15 (38) 0.377a Aortic valve replacement, n (%) 4 (5) 2 (5) 2 (5) 0.979b Patch size (cm2), mean ± SD 14 ± 8 12 ± 5 16 ± 10 0.070c Cardiopulmonary bypass time (min), mean ± SD 204 ± 58 209 ± 52 194 ± 68 0.349c Aortic cross-clamp time (min), mean ± SD 141 ± 58 148 ± 41 129 ± 43 0.124c All (n = 77) PES group (n = 38) Control group (n = 39) P-value Coronary angiography bypass graft, n (%) 41 (53) 20 (53) 21 (54) 0.915a Mitral valve repair, n (%) 45 (58) 21 (55) 24 (62) 0.576a Tricuspid valve repair, n (%) 26 (34) 11 (29) 15 (38) 0.377a Aortic valve replacement, n (%) 4 (5) 2 (5) 2 (5) 0.979b Patch size (cm2), mean ± SD 14 ± 8 12 ± 5 16 ± 10 0.070c Cardiopulmonary bypass time (min), mean ± SD 204 ± 58 209 ± 52 194 ± 68 0.349c Aortic cross-clamp time (min), mean ± SD 141 ± 58 148 ± 41 129 ± 43 0.124c a χ2 test. b Fisher’s exact test. c Student’s t-test. PES: programmed electrical stimulation; SD: standard deviation. Follow-up Patients were followed for 74 ± 35 months. Of the 77 patients, 74 (96%) patients had an ICD during the follow-up; 3 patients in the PES group did not receive an ICD based on the preference of the referring cardiologist (LVEF ≥35% at discharge, negative PES). The majority of the patients showed an improvement in the NYHA class from 3 at baseline to 2 at 1-year follow-up (P < 0.001). Mean LVEF improved from 27 ± 8% preoperatively to 36 ± 9% after 1 year (P < 0.001). No differences were observed between groups after 1 year (Table 3). Table 3: Follow-up All (n = 77) PES group (n = 38) Control group (n = 39) P-value Follow-up (months), mean ± SD 74 ± 35 61 ± 25 87 ± 39 <0.001a Death (all cause), n (%) 25 (32) 12 (32) 13 (33) 0.869b  Cardiac death, n (%) 14 (18) 9 (24) 7 (18) 0.688b ICD, n (%) 74 (96) 35 (92) 39 (100) 0.115b  Cardiac resynchronization therapy, n (%) 44 (57) 23 (61) 21 (54) 0.299b Antiarrhythmic drug, n (%) 36 (47) 17 (42) 19 (49) 0.726b  Sotalol ≥ 160mg/day, n (%) 26 (34) 13 (34) 13 (33) 0.953b  Amiodarone, n (%) 21 (27) 10 (26) 11 (28) 0.852b New atrial fibrillation, n (%) 33 (43) 15 (39) 18 (46) 0.544b NYHA 1-year follow-up, n (%) 0.052a  Class 1 28 (39) 19 (54) 9 (26)  Class 2 33 (47) 14 (39) 19 (53)  Class 3 10 (14) 3 (8) 7 (20) LVEF (%), mean ± SD 36 ± 9 36 ± 8 35 ± 9 0.845a LVESV index (ml/m2), mean ± SD 50 ± 19 50 ± 19 51 ± 19 0.829a LVEDV index (ml/m2), mean ± SD 77 ± 22 76 ± 23 79 ± 23 0.600a VA  Total, n 99 45 54 0.982b  Incidence ratio, episodes/total follow-up 0.017 0.016 0.019 1.19 (0.78–1.80)c  Occurrence, n (%) 28 (36) 14 (37) 14 (36) 0.931a  Time to first VA (months), median (IQR) 11 (2–27) 8 (2–26) 15 (4–29) 0.511d  Episodes, median (IQR) 3 (1–3) 3 (1–3) 3 (1–3) 0.982d  Cycle length (ms), mean ± SD 310 ± 58 314 ± 50 305 ± 67 0.699a  Ventricular fibrillation, n 15 8 7 0.841b ICD therapy, n (%) 26 (34) 12 (32) 14 (36) 0.222b  Antitachycardia pacing, n (%) 20 (26) 9 (24) 11 (28) 0.403e   Episodes, n 59 20 39  Shock, n (%) 11 (14) 6 (16) 5 (13) 0.699b   Episodes, n 18 9 9  Monitor zone, n (%) 8 (10) 6 (16) 2 (5) 0.092e   Episodes, n 22 16 6 Antiarrhythmic drug usage during first VA episode, n (%) 9 (12) 5 (13) 4 (10) 1.0e  Sotalol ≥ 160mg/day 6 4 2  Amiodarone 3 1 2 All (n = 77) PES group (n = 38) Control group (n = 39) P-value Follow-up (months), mean ± SD 74 ± 35 61 ± 25 87 ± 39 <0.001a Death (all cause), n (%) 25 (32) 12 (32) 13 (33) 0.869b  Cardiac death, n (%) 14 (18) 9 (24) 7 (18) 0.688b ICD, n (%) 74 (96) 35 (92) 39 (100) 0.115b  Cardiac resynchronization therapy, n (%) 44 (57) 23 (61) 21 (54) 0.299b Antiarrhythmic drug, n (%) 36 (47) 17 (42) 19 (49) 0.726b  Sotalol ≥ 160mg/day, n (%) 26 (34) 13 (34) 13 (33) 0.953b  Amiodarone, n (%) 21 (27) 10 (26) 11 (28) 0.852b New atrial fibrillation, n (%) 33 (43) 15 (39) 18 (46) 0.544b NYHA 1-year follow-up, n (%) 0.052a  Class 1 28 (39) 19 (54) 9 (26)  Class 2 33 (47) 14 (39) 19 (53)  Class 3 10 (14) 3 (8) 7 (20) LVEF (%), mean ± SD 36 ± 9 36 ± 8 35 ± 9 0.845a LVESV index (ml/m2), mean ± SD 50 ± 19 50 ± 19 51 ± 19 0.829a LVEDV index (ml/m2), mean ± SD 77 ± 22 76 ± 23 79 ± 23 0.600a VA  Total, n 99 45 54 0.982b  Incidence ratio, episodes/total follow-up 0.017 0.016 0.019 1.19 (0.78–1.80)c  Occurrence, n (%) 28 (36) 14 (37) 14 (36) 0.931a  Time to first VA (months), median (IQR) 11 (2–27) 8 (2–26) 15 (4–29) 0.511d  Episodes, median (IQR) 3 (1–3) 3 (1–3) 3 (1–3) 0.982d  Cycle length (ms), mean ± SD 310 ± 58 314 ± 50 305 ± 67 0.699a  Ventricular fibrillation, n 15 8 7 0.841b ICD therapy, n (%) 26 (34) 12 (32) 14 (36) 0.222b  Antitachycardia pacing, n (%) 20 (26) 9 (24) 11 (28) 0.403e   Episodes, n 59 20 39  Shock, n (%) 11 (14) 6 (16) 5 (13) 0.699b   Episodes, n 18 9 9  Monitor zone, n (%) 8 (10) 6 (16) 2 (5) 0.092e   Episodes, n 22 16 6 Antiarrhythmic drug usage during first VA episode, n (%) 9 (12) 5 (13) 4 (10) 1.0e  Sotalol ≥ 160mg/day 6 4 2  Amiodarone 3 1 2 P-value calculated between groups. a Student’s t-test. b χ2 test. c Incidence ratio (95% confidence interval). d Mann–Whitney U-test. e Fisher’s exact test. ICD: internal cardioverter defibrillator; IQR: interquartile range; LVEF: left ventricular ejection fraction; LVEDV: left ventricular end-diastolic volume; LVESV: left ventricular end-systolic volume; NYHA: New York Heart Association; PES: programmed electrical stimulation; SD: standard deviation; VA: ventricular arrhythmia. Table 3: Follow-up All (n = 77) PES group (n = 38) Control group (n = 39) P-value Follow-up (months), mean ± SD 74 ± 35 61 ± 25 87 ± 39 <0.001a Death (all cause), n (%) 25 (32) 12 (32) 13 (33) 0.869b  Cardiac death, n (%) 14 (18) 9 (24) 7 (18) 0.688b ICD, n (%) 74 (96) 35 (92) 39 (100) 0.115b  Cardiac resynchronization therapy, n (%) 44 (57) 23 (61) 21 (54) 0.299b Antiarrhythmic drug, n (%) 36 (47) 17 (42) 19 (49) 0.726b  Sotalol ≥ 160mg/day, n (%) 26 (34) 13 (34) 13 (33) 0.953b  Amiodarone, n (%) 21 (27) 10 (26) 11 (28) 0.852b New atrial fibrillation, n (%) 33 (43) 15 (39) 18 (46) 0.544b NYHA 1-year follow-up, n (%) 0.052a  Class 1 28 (39) 19 (54) 9 (26)  Class 2 33 (47) 14 (39) 19 (53)  Class 3 10 (14) 3 (8) 7 (20) LVEF (%), mean ± SD 36 ± 9 36 ± 8 35 ± 9 0.845a LVESV index (ml/m2), mean ± SD 50 ± 19 50 ± 19 51 ± 19 0.829a LVEDV index (ml/m2), mean ± SD 77 ± 22 76 ± 23 79 ± 23 0.600a VA  Total, n 99 45 54 0.982b  Incidence ratio, episodes/total follow-up 0.017 0.016 0.019 1.19 (0.78–1.80)c  Occurrence, n (%) 28 (36) 14 (37) 14 (36) 0.931a  Time to first VA (months), median (IQR) 11 (2–27) 8 (2–26) 15 (4–29) 0.511d  Episodes, median (IQR) 3 (1–3) 3 (1–3) 3 (1–3) 0.982d  Cycle length (ms), mean ± SD 310 ± 58 314 ± 50 305 ± 67 0.699a  Ventricular fibrillation, n 15 8 7 0.841b ICD therapy, n (%) 26 (34) 12 (32) 14 (36) 0.222b  Antitachycardia pacing, n (%) 20 (26) 9 (24) 11 (28) 0.403e   Episodes, n 59 20 39  Shock, n (%) 11 (14) 6 (16) 5 (13) 0.699b   Episodes, n 18 9 9  Monitor zone, n (%) 8 (10) 6 (16) 2 (5) 0.092e   Episodes, n 22 16 6 Antiarrhythmic drug usage during first VA episode, n (%) 9 (12) 5 (13) 4 (10) 1.0e  Sotalol ≥ 160mg/day 6 4 2  Amiodarone 3 1 2 All (n = 77) PES group (n = 38) Control group (n = 39) P-value Follow-up (months), mean ± SD 74 ± 35 61 ± 25 87 ± 39 <0.001a Death (all cause), n (%) 25 (32) 12 (32) 13 (33) 0.869b  Cardiac death, n (%) 14 (18) 9 (24) 7 (18) 0.688b ICD, n (%) 74 (96) 35 (92) 39 (100) 0.115b  Cardiac resynchronization therapy, n (%) 44 (57) 23 (61) 21 (54) 0.299b Antiarrhythmic drug, n (%) 36 (47) 17 (42) 19 (49) 0.726b  Sotalol ≥ 160mg/day, n (%) 26 (34) 13 (34) 13 (33) 0.953b  Amiodarone, n (%) 21 (27) 10 (26) 11 (28) 0.852b New atrial fibrillation, n (%) 33 (43) 15 (39) 18 (46) 0.544b NYHA 1-year follow-up, n (%) 0.052a  Class 1 28 (39) 19 (54) 9 (26)  Class 2 33 (47) 14 (39) 19 (53)  Class 3 10 (14) 3 (8) 7 (20) LVEF (%), mean ± SD 36 ± 9 36 ± 8 35 ± 9 0.845a LVESV index (ml/m2), mean ± SD 50 ± 19 50 ± 19 51 ± 19 0.829a LVEDV index (ml/m2), mean ± SD 77 ± 22 76 ± 23 79 ± 23 0.600a VA  Total, n 99 45 54 0.982b  Incidence ratio, episodes/total follow-up 0.017 0.016 0.019 1.19 (0.78–1.80)c  Occurrence, n (%) 28 (36) 14 (37) 14 (36) 0.931a  Time to first VA (months), median (IQR) 11 (2–27) 8 (2–26) 15 (4–29) 0.511d  Episodes, median (IQR) 3 (1–3) 3 (1–3) 3 (1–3) 0.982d  Cycle length (ms), mean ± SD 310 ± 58 314 ± 50 305 ± 67 0.699a  Ventricular fibrillation, n 15 8 7 0.841b ICD therapy, n (%) 26 (34) 12 (32) 14 (36) 0.222b  Antitachycardia pacing, n (%) 20 (26) 9 (24) 11 (28) 0.403e   Episodes, n 59 20 39  Shock, n (%) 11 (14) 6 (16) 5 (13) 0.699b   Episodes, n 18 9 9  Monitor zone, n (%) 8 (10) 6 (16) 2 (5) 0.092e   Episodes, n 22 16 6 Antiarrhythmic drug usage during first VA episode, n (%) 9 (12) 5 (13) 4 (10) 1.0e  Sotalol ≥ 160mg/day 6 4 2  Amiodarone 3 1 2 P-value calculated between groups. a Student’s t-test. b χ2 test. c Incidence ratio (95% confidence interval). d Mann–Whitney U-test. e Fisher’s exact test. ICD: internal cardioverter defibrillator; IQR: interquartile range; LVEF: left ventricular ejection fraction; LVEDV: left ventricular end-diastolic volume; LVESV: left ventricular end-systolic volume; NYHA: New York Heart Association; PES: programmed electrical stimulation; SD: standard deviation; VA: ventricular arrhythmia. Ventricular arrhythmia occurrence and survival In 28 of 74 (38%) patients, 99 VA episodes were recorded on ICD [VACL 310 ± 58 ms, 3 (IQR 1–3) VAs per patient], which prompted appropriate ICD therapy in 26 of 28 (93%) patients; 20 (25%) patients received ATP for 58 VAs and 11 (14%) patients received ≥1 shocks for 18 VAs. In 10 patients, 15 VAs were registered in the VF zone. No differences were found between groups regarding the type of ICD therapy (Table 3). Two patients in the PES group had 2 VAs registered only in the monitor zone of the ICD and did not receive any ICD therapy. None of the patients without ICD had documented or suspected sustained VA. Of the 11 patients, 8 patients with a negative outcome at PES had no VA occurrences that generated a negative predictive value of 73%. Median time to first VA was 11 months (IQR 2–27). Of the 28 patients, 9 (32%) patients experienced a first VA while on antiarrhythmic drugs. Antiarrhythmic drugs were initiated because of postoperative spontaneous VA (n = 4) or atrial fibrillation/flutter (n = 5). VA occurrence was similar between groups; 14 of 38 (37%) patients in the PES group experienced 45 VAs [CL 314 ± 50 ms; 3 (IQR 1–3) VAs per patient], and 14 of 39 (36%) patients in the control group experienced 54 VAs [CL 305 ± 67 ms, 3 (IQR 1–3) VAs per patient]. VA-free survival was 63% at 5 years for the entire cohort and similar between groups (Fig. 1A): 61% for the PES group and 65% for the control group (hazard ratio 1.13, P = 0.750; after adjusting for confounders, hazard ratio 1.67, P = 0.290; Table 4). A similar hazard ratio was obtained after propensity score adjustment: 1.52 (P = 0.39). On performing multivariable Cox regression analyses for VA occurrence, LVEF at baseline influenced VA occurrence: Lower LVEF increased the risk for VA during follow-up. VA characteristics did not differ between groups (Table 3). One patient in the control group underwent successful catheter ablation of 2 presumptive clinical VAs 46 months after discharge and was free from VA afterwards. Table 4: Cox regression analyses: VA-free survival Univariable Multivariable HR (95% CI) P-value HR (95% CI) P-value Age (years) 1.02 (0.98–1.07) 0.28 1.03 (0.99–1.08) 0.13 LVEF baseline 0.97 (0.92–1.02) 0.19 0.94 (0.89–1.00) 0.03 NYHA classa 1.15 (0.53–2.50) 0.72 1.28 (0.51–3.18) 0.60 PES group 1.13 (0.53–2.41) 0.75 1.67 (0.65–4.30) 0.29 Primary reperfusion 0.81 (0.35–1.84) 0.61 0.83 (0.35–1.99) 0.68 Gender 1.81 (0.62–5.23) 0.28 2.62 (0.87–7.89) 0.09 Univariable Multivariable HR (95% CI) P-value HR (95% CI) P-value Age (years) 1.02 (0.98–1.07) 0.28 1.03 (0.99–1.08) 0.13 LVEF baseline 0.97 (0.92–1.02) 0.19 0.94 (0.89–1.00) 0.03 NYHA classa 1.15 (0.53–2.50) 0.72 1.28 (0.51–3.18) 0.60 PES group 1.13 (0.53–2.41) 0.75 1.67 (0.65–4.30) 0.29 Primary reperfusion 0.81 (0.35–1.84) 0.61 0.83 (0.35–1.99) 0.68 Gender 1.81 (0.62–5.23) 0.28 2.62 (0.87–7.89) 0.09 a NYHA class as categorical covariate did not alter outcome. CI: confidence interval; HR: hazard ratio; LVEF: left ventricular ejection fraction; NYHA: New York Heart Association; PES: programmed electrical stimulation; VA: ventricular arrhythmia. Table 4: Cox regression analyses: VA-free survival Univariable Multivariable HR (95% CI) P-value HR (95% CI) P-value Age (years) 1.02 (0.98–1.07) 0.28 1.03 (0.99–1.08) 0.13 LVEF baseline 0.97 (0.92–1.02) 0.19 0.94 (0.89–1.00) 0.03 NYHA classa 1.15 (0.53–2.50) 0.72 1.28 (0.51–3.18) 0.60 PES group 1.13 (0.53–2.41) 0.75 1.67 (0.65–4.30) 0.29 Primary reperfusion 0.81 (0.35–1.84) 0.61 0.83 (0.35–1.99) 0.68 Gender 1.81 (0.62–5.23) 0.28 2.62 (0.87–7.89) 0.09 Univariable Multivariable HR (95% CI) P-value HR (95% CI) P-value Age (years) 1.02 (0.98–1.07) 0.28 1.03 (0.99–1.08) 0.13 LVEF baseline 0.97 (0.92–1.02) 0.19 0.94 (0.89–1.00) 0.03 NYHA classa 1.15 (0.53–2.50) 0.72 1.28 (0.51–3.18) 0.60 PES group 1.13 (0.53–2.41) 0.75 1.67 (0.65–4.30) 0.29 Primary reperfusion 0.81 (0.35–1.84) 0.61 0.83 (0.35–1.99) 0.68 Gender 1.81 (0.62–5.23) 0.28 2.62 (0.87–7.89) 0.09 a NYHA class as categorical covariate did not alter outcome. CI: confidence interval; HR: hazard ratio; LVEF: left ventricular ejection fraction; NYHA: New York Heart Association; PES: programmed electrical stimulation; VA: ventricular arrhythmia. Figure 1: View largeDownload slide Survival analyses. (A) The Kaplan–Meier curves of 5-year VA-free survival, groups compared using multivariable Cox regression model. (B) The Kaplan–Meier curves of 5-year overall survival, groups compared using multivariable Cox regression model. Curves represent the different preoperative strategies of yes/no PES. PES: programmed electrical stimulation; VA: ventricular arrhythmia. Figure 1: View largeDownload slide Survival analyses. (A) The Kaplan–Meier curves of 5-year VA-free survival, groups compared using multivariable Cox regression model. (B) The Kaplan–Meier curves of 5-year overall survival, groups compared using multivariable Cox regression model. Curves represent the different preoperative strategies of yes/no PES. PES: programmed electrical stimulation; VA: ventricular arrhythmia. Twenty-five (32%) patients died during follow-up: 16 (64%) patients due to heart failure and 9 patients due to non-cardiac causes. No arrhythmic deaths were reported. One patient in the PES group received an LV assist device as destination therapy 58 months after SVR and 1 patient in the control group underwent heart transplantation after 28 months; both were censored for further follow-up afterwards. The Kaplan–Meier analysis revealed a 5-year overall survival rate of 78%. No difference in the 5-year overall survival was observed between groups (the PES group versus the control group: 79% vs 78%, Fig. 1B): unadjusted hazard ratio 1.05, P = 0.932 and adjusted hazard ratio 1.62, P = 0.514. A similar hazard ratio was obtained after propensity score adjustment: 1.41 (P = 0.64). On performing multivariable analyses, only older age remained associated with worse overall survival (Table 5). Table 5: Cox regression analyses: overall survival Univariable Multivariable HR (95% CI) P-value HR (95% CI) P-value Age (years) 1.10 (1.02–1.18) 0.02 1.12 (1.03–1.22) <0.01 LVEF baseline 0.98 (0.91–1.05) 0.59 0.94 (0.87–1.024) 0.16 NYHA classa 1.98 (0.64–6.10) 0.24 2.54 (0.72–8.91) 0.15 PES group 1.05 (0.35–3.12) 0.93 1.62 (0.38–6.85) 0.51 Primary reperfusion 0.41 (0.09–1.84) 0.24 0.45 (0.09–2.25) 0.33 Gender 2.05 (0.45–9.25) 0.35 2.45 (0.48–12.49) 0.28 Univariable Multivariable HR (95% CI) P-value HR (95% CI) P-value Age (years) 1.10 (1.02–1.18) 0.02 1.12 (1.03–1.22) <0.01 LVEF baseline 0.98 (0.91–1.05) 0.59 0.94 (0.87–1.024) 0.16 NYHA classa 1.98 (0.64–6.10) 0.24 2.54 (0.72–8.91) 0.15 PES group 1.05 (0.35–3.12) 0.93 1.62 (0.38–6.85) 0.51 Primary reperfusion 0.41 (0.09–1.84) 0.24 0.45 (0.09–2.25) 0.33 Gender 2.05 (0.45–9.25) 0.35 2.45 (0.48–12.49) 0.28 a NYHA class as categorical covariate did not alter the outcome. CI: confidence interval; HR: hazard ratio; LVEF: left ventricular ejection fraction; NYHA: New York Heart Association; PES: programmed electrical stimulation. Table 5: Cox regression analyses: overall survival Univariable Multivariable HR (95% CI) P-value HR (95% CI) P-value Age (years) 1.10 (1.02–1.18) 0.02 1.12 (1.03–1.22) <0.01 LVEF baseline 0.98 (0.91–1.05) 0.59 0.94 (0.87–1.024) 0.16 NYHA classa 1.98 (0.64–6.10) 0.24 2.54 (0.72–8.91) 0.15 PES group 1.05 (0.35–3.12) 0.93 1.62 (0.38–6.85) 0.51 Primary reperfusion 0.41 (0.09–1.84) 0.24 0.45 (0.09–2.25) 0.33 Gender 2.05 (0.45–9.25) 0.35 2.45 (0.48–12.49) 0.28 Univariable Multivariable HR (95% CI) P-value HR (95% CI) P-value Age (years) 1.10 (1.02–1.18) 0.02 1.12 (1.03–1.22) <0.01 LVEF baseline 0.98 (0.91–1.05) 0.59 0.94 (0.87–1.024) 0.16 NYHA classa 1.98 (0.64–6.10) 0.24 2.54 (0.72–8.91) 0.15 PES group 1.05 (0.35–3.12) 0.93 1.62 (0.38–6.85) 0.51 Primary reperfusion 0.41 (0.09–1.84) 0.24 0.45 (0.09–2.25) 0.33 Gender 2.05 (0.45–9.25) 0.35 2.45 (0.48–12.49) 0.28 a NYHA class as categorical covariate did not alter the outcome. CI: confidence interval; HR: hazard ratio; LVEF: left ventricular ejection fraction; NYHA: New York Heart Association; PES: programmed electrical stimulation. Encircling cryoablation and ventricular arrhythmia characteristics Overall, 11 of 27 (41%) patients with concomitant EC experienced 37 VA episodes [median 2 (IQR 1–3) episodes per patient]. VACL did not differ between patients with or without EC: 308 ± 46 ms vs 311 ± 66, P = 0.919, respectively. Five (14%) VAs were terminated by ICD shock and 19 (51%) VAs by ATP. The remaining 13 (35%) VAs were registered in the ICD monitor zone. There were no differences in the type of ICD therapy between patients with or without EC. DISCUSSION This study is the first to systematically evaluate the incidence, type and timing of VA in patients who underwent PES-guided EC concomitant to SVR for primary prevention of VA, thereby targeting 2 potential VA mechanisms: scar-related re-entry and wall stress. The main findings are as follows: (i) the majority of the patients referred for SVR without previously documented VA was inducible for aneurysm-related VA; (ii) during follow-up, more than one-third of the patients experienced appropriate ICD therapy, despite concomitant EC targeting the scar borderzone and significant haemodynamic improvement; (iii) no difference in VA occurrence, VACL and ICD therapy was observed during the long-term follow-up between patients with PES-guided concomitant EC and those without preoperative evaluation and concomitant treatment. This investigation comprised a homogeneous patient group referred for heart failure treatment because of ischaemic cardiomyopathy, with an anterior aneurysm after infarction and none treated with amiodarone. Excellent outcome of heart failure parameters after SVR for this indication was previously reported by our group [16]. The STICH trial has reported no clinical benefit of SVR when added to surgery in patients scheduled for coronary artery bypass grafting [17]. As the primary inclusion criterion for this trial was acceptation for coronary artery bypass grafting for significant coronary artery disease, we believe that the findings of this trial are not fully applicable to the populations reported in this study. Preoperative ventricular arrhythmia inducibility 71% of the study group was inducible for an aneurysm-related VA prior to surgery, using the standardized and complete PES protocol. Others have reported lower inducibility rates, ranging from 22% to 58%. However, the included patients were more heterogeneous (with/without apical aneurysm, anterior/non-anterior infarction, NYHA Class 1–3, many on sotalol/amiodarone and LVEF >40%), and in several studies, the induction protocol was less extensive, which is likely to influence inducibility rates in scar-related VA [13, 18–21]. Induction of a monomorphic re-entrant VA indicates the presence of an arrhythmogenic substrate and has been associated with VA occurrence and sudden death in patients after myocardial infarction, especially in patients with an LV aneurysm [13, 14, 22]. Based on the VA morphology, all except 3 VAs had an exit site at the aneurysm scar borderzone specifically involving the inferior apical septal segments. Therefore, targeting the scar borderzone by cryoablation may abolish at least parts of the substrate for these VA. Ventricular arrhythmia occurrence after surgical ventricular reconstruction Previous studies have demonstrated that the substrate for re-entrant VA could persist after SVR and might lead to VA occurrence during follow-up [10, 23]. This might be partly due to the incomplete elimination of the VA substrate by SVR, as a significant portion of the myocardial scar is left behind the inserted patch for stability and haemostasis. The excluded portion of the scar containing the VA re-entry circuit can no longer be approached by endocardial catheter ablation, which may further justify preventive substrate elimination [9]. In the historical control group without the additional PES-guided EC, 36% experienced spontaneous VA during the long-term follow-up, supporting the importance of preventive methods to identify and target possible VA substrates. Of importance, in the PES group, 71% of which underwent EC of the scar borderzone, a similar high VA occurrence rate was registered (37%). The groups were not randomized, but Cox regression testing for possible confounders does not suggest that PES-guided concomitant EC prevents late VA. Because VAs were registered in 41% of patients who underwent EC of the scar borderzone, the technique seems to be insufficient to eliminate the VA substrate in our population. Catheter mapping studies of postinfarct VA have shown that although re-entry circuit exit sites are usually located at the scar borderzone, which may also involve the mid-wall and subepicardial layers, the critical isthmus is often found in the electroanatomical dense scar [3, 4, 24, 25]. A prior animal study reported that endocardial cryoablation lesions reach a depth of approximately 4.8 mm [26]. Endocardial cryolesions, especially at the septal scar borderzone, may not create transmural or deep lesions and may not be sufficient to eliminate or exclude the VA substrate, allowing for circuits to remain or the re-entrant circuit to exit. VA occurrence rate after EC in this population without prior VA was higher than previously described recurrence rates in patients who underwent EC for the treatment of recurrent VA [2, 8, 10–12]. This may be partly explained by the large proportion of patients with an ICD (96%) in this investigation, allowing for reliable monitoring of VA recurrence. The high ICD implantation rate is different from the majority of prior studies with implantation rates of only up to 9.6% after SVR [2, 10–12], except for the investigation of O’Neill et al. [8], in which 48% of patients were discharged with an ICD. Differences in surgical techniques and the frequent use of amiodarone in the prior studies might also have contributed to lower VA recurrence rates. Of importance, differences in the VA substrate might exist between patients with, as in previous studies, and without, as in this study, spontaneous VA before surgery. Although previous studies mainly included patients with haemodynamically tolerated and often slow VAs [9, 11, 27], the observed VAs in this study were often fast and an important number required ICD shocks to be terminated. As the underlying substrate determines the VA characteristics, like to CL, the occurrence of fast VAs might reflect differences in the VA substrate between the studied population and the patients in previous studies [28]. Fast VAs as observed in our cohort may be due to small anatomical or even functional re-entry circuits. The substrate for these fast VAs may not be sufficiently targeted by EC of the scar borderzone. The fact that late VAs in both groups were similar regarding CL and response to ATP supports the conclusion that EC had no sufficient impact on the VA substrate. Progressive remodelling and LV re-enlargement might occur after surgery contributing to arrhythmogenity, which is also supported by the high occurrence rate of atrial fibrillation in patients with VA [9, 21]. Survival We reported a good overall survival rate of 78% at 5-year follow-up for the total study population. This is comparable with other centres with a large experience in SVR (70–82% 5-year survival) [2, 10]. No arrhythmic deaths occurred. The observed fast VAs terminated by ICD shock in 11 (14%) patients might be considered as aborted arrhythmic deaths. Two prior studies reported similar rates of arrhythmic deaths (17% and 20%) [7, 12]. In contrast, in 1 study, cardiac death constituted 19% of late mortality at follow-up; however, sudden cardiac death rate was only 2.5% [2]. Although not all ICD therapy equals aborted sudden death, most of the study period was during the time with relatively short detection times, and prior to MADIT-RIT trial results were published, symptomatic and potential fatal VAs do occur [29]. Clinical implications The majority of the patients referred for SVR and without prior VAs were inducible for aneurysm-related monomorphic VA prior to SVR. Although all preoperatively inducible patients underwent concomitant EC targeting the scar borderzone, this was not sufficient to prevent VA in a considerable number of patients. We observed a clinically relevant high VA occurrence rate after surgery in both the PES group and the control group. Considering the good long-term survival and high incidence of appropriate ICD therapies, other concomitant antiarrhythmic surgical approaches targeting the potential arrhythmogenic substrate such as endocardectomy should be explored, because endocardial EC alone is insufficient [30]. According to the current guidelines, patients after SVR, independently of concomitant antiarrhythmic treatment, should receive an ICD to prevent sudden cardiac death if they meet the criteria for prophylactic ICD implantation. Limitations Because of the retrospective nature of the study, the number of patients included is limited. As a consequence of the inclusion of the historical control group, follow-up duration varied among patients. Furthermore, this study was non-randomized. To adjust for baseline imbalances, a Cox regression analysis was performed, and the results were checked with a Cox model adjusted for propensity score. Despite this evaluation, it should be kept in mind that neither a standard Cox model nor a propensity score could balance for unmeasured confounding. Hence, the residual confounding should still be considered one of the explanations for our results. The adjusted hazard ratio for the PES group increases after adjusting for confounders. This might partly reflect a poorer baseline condition of the control group. Because the confidence interval of the adjusted hazard ratio is very wide, no definite conclusions with regard to the relation between PES-guided EC and outcome could be drawn. Comparison between patients with inducible aneurysm-related VAs but without concomitant EC was not performed. However, because of the reported favourable results for non-mapping-guided cryoablation to treat VA, not performing cryoablation in these high-risk patients was considered unethical. Although the treatment strategy was not allocated in a randomized fashion, groups were comparable and treated by the same team. Because the cohort was small, the negative predictive value should be interpreted with caution. CONCLUSION The majority of the patients referred for SVR without previously documented VAs was inducible for aneurysm-related fast monomorphic VA. Despite concomitant EC targeting the scar borderzone, postoperative haemodynamic improvement and low all-cause mortality, 5-year VA-free survival was only 64%. No difference in VA occurrence or ICD therapy was observed between patients with or without PES-guided concomitant EC. 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TI - Programmed electrical stimulation-guided encircling cryoablation concomitant to surgical ventricular reconstruction for primary prevention of ventricular arrhythmias
JF - European Journal of Cardio-Thoracic Surgery
DO - 10.1093/ejcts/ezx496
DA - 2018-01-22
UR - https://www.deepdyve.com/lp/oxford-university-press/programmed-electrical-stimulation-guided-encircling-cryoablation-p0WgaX5GQH
SP - 1
EP - 105
VL - Advance Article
IS - 1
DP - DeepDyve
ER -