Validation of a prediction model for early reconnection after cryoballoon ablation.

BACKGROUND: We previously developed an early reconnection/dormant conduction (ERC) prediction model for cryoballoon ablation to avoid a 30-min waiting period with adenosine infusion. We now aimed to validate this model based on time to isolation, number of unsuccessful cryo-applications, and nadir balloon temperature. METHODS: Consecutive atrial fibrillation patients who underwent their first cryoballoon ablation in 2018-2019 at the Leiden University Medical Center were included. Model performance at the previous and at a new optimal cutoff value was determined. RESULTS: A total of 201 patients were included (85.57% paroxysmal AF, 139 male, median age 61 years (IQR 53-69)). ERC was found in 35 of 201 included patients (17.41%) and in 41 of 774 veins (5.30%). In the present study population, the previous cutoff value of - 6.7 provided a sensitivity of 37.84% (previously 70%) and a specificity of 89.07% (previously 86%). Shifting the cutoff value to - 7.2 in both study populations resulted in a sensitivity of 72.50% and 72.97% and a specificity of 78.22% and 78.63% in data from the previous and present study respectively. Negative predictive values were 96.55% and 98.11%. Applying the model on the 101 patients of the present study with all necessary data for all veins resulted in 43 out of 101 patients (43%) not requiring a 30-min waiting period with adenosine testing. Two patients (2%) with ERC would have been missed when applying the model. CONCLUSIONS: The previously established ERC prediction model performs well, recommending its use for centers routinely using adenosine testing following PVI.

Area-weighted unipolar voltage to predict heart failure outcomes in patients with ischaemic cardiomyopathy and ventricular tachycardia.

AIMS: Patients with ischaemic cardiomyopathy (ICM) referred for catheter ablation of ventricular tachycardia (VT) are at risk for end-stage heart failure (HF) due to adverse remodelling. Local unipolar voltages (UV) decrease with loss of viable myocardium. A UV parameter reflecting global viable myocardium may predict prognosis. We evaluate if a newly proposed parameter, area-weighted unipolar voltage (awUV), can predict HF-related outcomes [HFO; HF death/left ventricular (LV) assist device/heart transplant] in ICM. METHODS AND RESULTS: From endocardial voltage maps of consecutive patients with ICM referred for VT ablation, awUV was calculated by weighted interpolation of local UV. Associations between clinical and mapping parameters and HFO were evaluated and validated in a second cohort. The derivation cohort consisted of 90 patients [age 68 ±8 years; LV ejection fraction (LVEF) 35% interquartile range (IQR) (24-40)] and validation cohort of 60 patients [age 67 ± 9, LVEF 39% IQR (29-45)]. In the derivation cohort, during a median follow-up of 45 months [IQR (34-83)], 36 (43%) patients died and 23 (26%) had HFO. Patients with HFO had lower awUV [4.51 IQR (3.69-5.31) vs. 7.03 IQR (6.08-9.2), P < 0.001]. A reduction in awUV [optimal awUV (5.58) cut-off determined by receiver operating characteristics analysis] was a strong predictor of HFO (3-year HFO survival 97% vs. 57%). The cut-off value was confirmed in the validation cohort (2-year HFO-free survival 96% vs. 60%). CONCLUSION: The newly proposed parameter awUV, easily available from routine voltage mapping, may be useful at identifying ICM patients at high risk for HFO.

Head-to-Head Comparison of T1 Mapping and Electroanatomical Voltage Mapping in Patients With Ventricular Arrhythmias.

BACKGROUND: Electroanatomical voltage mapping (EAVM) has been compared with late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR), which cannot delineate diffuse fibrosis. T1-mapping CMR overcomes the limitations of LGE-CMR, but it has not been directly compared against EAVM. OBJECTIVES: This study aims to assess the relationship between left ventricular (LV) endocardial voltage obtained by EAVM and extracellular volume (ECV) obtained by T1 mapping. METHODS: The study investigated patients who underwent endocardial EAVM for ventricular arrhythmias (CARTO 3, Biosense Webster) together with preprocedural contrast-enhanced T1 mapping (Ingenia 3T, Philips Healthcare). After image integration, EAVM datapoints were projected onto LGE-CMR and ECV-encoded images. Average values of unipolar voltage (UV), bipolar voltage (BV), LGE transmurality, and ECV were merged from corresponding cardiac segments (6 per slice) and pooled for analysis. RESULTS: The analysis included data from 628 segments from 18 patients (57 ± 13 years of age, 17% females, LV ejection fraction 48% ± 14%, nonischemic/ischemic cardiomyopathy/controls: 8/6/4 patients). Based on the 95th and 5th percentile values obtained from the controls, ECV >33%, BV <2.9 mV, and UV <6.7 mV were considered abnormal. There was a significant inverse association between voltage and ECV, but only in segments with abnormal ECV. Increased ECV could predict abnormal BV and UV with acceptable accuracy (area under the curve of 0.78 [95% CI: 0.74-0.83] and 0.84 [95% CI: 0.79-0.88]). CONCLUSIONS: This study found a significant inverse relationship between LV endocardial voltage and ECV. Real-time integration of T1 mapping may guide catheter mapping and may allow identification of areas of diffuse fibrosis potentially related to ventricular arrhythmias.

Volume-Weighted Unipolar Voltage Predicts Heart Failure Mortality in Patients With Dilated Cardiomyopathy and Ventricular Arrhythmias.

BACKGROUND: Patients with dilated cardiomyopathy (DCM) who are undergoing catheter ablation of ventricular arrhythmias (VAs) are at risk of rapidly progressive heart failure (HF). Endocardial voltages decrease with loss of viable myocardium. Global left ventricular (LV) voltage as a surrogate for the amount of remaining viable myocardium may predict prognosis. OBJECTIVES: This study evaluated whether the newly proposed parameter volume-weighted (vw) unipolar voltage (UV) can predict HF-related adverse outcomes (HFOs), including death, heart transplantation, or ventricular assist device implantation, in DCM. METHODS: In consecutive patients with DCM referred for VA ablation, vwUV was calculated by mathematically integrating UV over the left ventricle, divided by the endocardial LV surface area and wall thickness. Patients were followed for HFOs. RESULTS: A total of 103 patients (57 ± 14 years of age; left ventricular ejection fraction [LVEF], 39% ± 13%) were included. Median vwUV was 9.75 (IQR: 7.27-12.29). During a median follow-up of 24 months (IQR: 8-47 months), 25 patients (24%) died, and 16 had HFOs 7 months (IQR: 1-18 months) after ablation. Patients with HFOs had significantly lower LVEF (29% ± 10% vs 41% ± 12%), vw bipolar voltage (BV) (3.00 [IQR: 2.47-3.53] vs 5.00 [IQR: 4.12-5.73]), and vwUV (5.94 [IQR: 5.28-6.55] vs 10.37 [IQR: 8.82-12.81]; all P < 0.001), than patients without HFOs. In Cox regression analysis and goodness-of-fit tests, vwUV was the strongest and independent predictor for HFOs (HR: 3.68; CI: 2.09-6.45; likelihood ratio chi-square, 33.05; P < 0.001). CONCLUSIONS: The novel parameter vwUV, as a surrogate for the amount of viable myocardium, identifies patients with DCM with VA who are at high risk for HF progression and mortality.

Very High-Power Ablation for Contiguous Pulmonary Vein Isolation: Results From the Randomized POWER PLUS Trial.

BACKGROUND: Very high-power, short-duration (90-W/4-second) ablation for pulmonary vein isolation (PVI) may reduce procedural times. However, shorter applications with higher power may impact lesion quality. OBJECTIVES: In this multicenter, randomized controlled trial, the authors compared procedural efficiency, efficacy, and safety of PVI using 90-W/4-second ablation to 35/50-W ablation. METHODS: Patients with paroxysmal or persistent atrial fibrillation undergoing first-time PVI were randomized to pulmonary vein encirclement with contiguous applications using very high-power, short-duration applications (90 W over 4 seconds) or 35/50-W applications (titrated up to ablation index >550 anteriorly and >400 posteriorly). Prospective endpoints were procedural efficiency (procedure time and first-pass isolation), safety (including esophageal endoscopic evaluation), and 6-month effectiveness using repetitive Holter monitoring. RESULTS: A total of 180 patients were randomized, 90 to the 90-W group (mean age: 64.2 ± 8.9 years) and 90 to the 35/50-W group (mean age: 62.3 ± 10.8 years). Procedural time was shorter in the 90-W group vs the 35/50-W group (70 [IQR: 60-80] minutes vs 75 [IQR: 65-88.3] minutes; P = 0.009). A nonsignificant trend towards lower rates of first-pass isolation was seen in the 90-W group (83.9% vs 90%; P = 0.0852). No major complications were observed in both groups with esophageal injury occurring in 1 patient per group. At 6 months, 17% of patients in the 90-W group vs 15% in the 35/50-W group experienced recurrent arrhythmia (P = 0.681). CONCLUSIONS: Contiguous ablation using very high-power, short-duration applications results in a significant but modest reduction in procedure time with similar safety and 6-month efficacy vs a conventional approach. A hybrid approach combining both ablation modalities might be the most optimal strategy. (POWER PLUS [Very High Power Ablation in Patients With Atrial Fibrillation Schedule for a First Pulmonary Vein Isolation]; NCT04784013).

Unipolar voltage mapping in right ventricular cardiomyopathy: pitfalls, solutions and advantages.

AIMS: Endocardial unipolar and bipolar voltage mapping (UVM/BVM) of the right ventricle (RV) are used for transmural substrate delineation. However, far-field electrograms (EGMs) and EGM changes due to injury current may influence automatically generated UVM. Epicardial BVM is considered less accurate due to the impact of fat thickness (FT). Data on epicardial UVM are sparse. The aim of the study is two-fold: to assess the influence of the manually corrected window-of-interest on UVM and the potential role of epicardial UVM in RV cardiomyopathies. METHODS AND RESULTS: Consecutive patients who underwent endo-epicardial RV mapping with computed-tomography (CT) integration were included. Mapping points were superimposed on short-axis CT slices and correlated with local FT. All points were manually re-analysed and the window-of-interest was adjusted to correct for false high unipolar voltage (UV). For opposite endo-epicardial point-pairs, endo-epicardial bipolar voltage (BV) and UV were correlated for different FT categories. A total of 3791 point-pairs of 33 patients were analysed. In 69% of endocardial points and 63% of epicardial points, the window-of-interest needed to be adjusted due to the inclusion of far-field EGMs, injury current components, or RV-pacing artifacts. The Pearson correlation between corrected endo-epicardial BV and UV was lower for point-pairs with greater FT; however, this correlation was much stronger and less influenced by fat for UV. CONCLUSION: At the majority of mapping sites, the window-of-interest needs to be manually adjusted for correct UVM. Unadjusted UVM underestimates low UV regions. Unipolar voltage seems to be less influenced by epicardial fat, suggesting a promising role for UVM in epicardial substrate delineation.

Pleomorphic Ventricular Tachycardia in Dilated Cardiomyopathy Predicts Ventricular Tachycardia Recurrence After Ablation Independent From Cardiac Function: Comparison With Patients With Ischemic Heart Disease.

BACKGROUND: In dilated cardiomyopathy (DCM), outcome after catheter ablation of ventricular tachycardia (VT) is modest, compared with ischemic heart disease (IHD). Pleomorphic VT (PL-VT) has been associated with fibrotic remodeling and end-stage heart failure in IHD. The prognostic role of PL-VT in DCM is unknown. METHODS: Consecutive IHD (2009-2016) or DCM (2008-2018) patients undergoing ablation for monomorphic VT were included. PL-VT was defined as ≥1 spontaneous change of the 12-lead VT-morphology during the same induced VT episode. Patients were followed for VT recurrence and mortality. RESULTS: A total of 247 patients (86% men; 63±13 years; IHD n=152; DCM n=95) underwent ablation for monomorphic VT. PL-VT was observed in 22 and 29 patients with IHD and DCM, respectively (14% versus 31%, P=0.003). In IHD, PL-VT was associated with lower LVEF (28±9% versus 34±12%, P=0.02) and only observed in those with LVEF<40%. In contrast, in DCM, PL-VT was not related to LVEF and induced in 27% of patients with LVEF>40%. During a median follow-up of 30 months, 79 (32%) patients died (IHD 48; DCM 31; P=0.88) and 120 (49%) had VT recurrence (IHD 59; DCM 61; P<0.001). PL-VT was associated with mortality in IHD but not in DCM. In IHD, VT recurrence was independently associated with LVEF, number of induced VTs, and procedural noncomplete success. Of note, in DCM, PL-VT (HR, 2.62 [95% CI, 1.47-4.69]), pathogenic mutation (HR, 2.13 [95% CI, 1.16-3.91]), and anteroseptal VT substrate (HR, 1.75 [95% CI, 1.00-3.07]) independently predicted VT recurrence. CONCLUSIONS: In IHD, PL-VT was associated with low LVEF and mortality. In DCM, PL-VT was not associated with mortality but a predictor of VT recurrence independent from LVEF. PL-VT in DCM may indicate a specific arrhythmic substrate difficult to control by current ablation techniques.

Clinical Outcomes in Patients With Dilated Cardiomyopathy and Ventricular Tachycardia.

BACKGROUND: Recurrent ventricular tachycardia (VT) due to dilated cardiomyopathy (DCM) is difficult to treat, and long-term outcome data are limited. OBJECTIVES: The aim of this study was to identify predictors of mortality or heart transplantation (HTx) and VT recurrence. METHODS: Consecutive patients with DCM accepted for radiofrequency catheter ablation (RFCA) of VT at 9 centers were prospectively enrolled and followed. RESULTS: Of 281 consecutive patients (mean age 60 ± 13 years, 85% men, mean left ventricular ejection fraction [LVEF] 36% ± 12%), 35% had VT storm, 20% had incessant VT, and amiodarone was unsuccessful in 68%. During follow-up of 21 months (IQR: 6-30 months), 67 patients (24%) died or underwent HTx, and 138 (49%) had VT recurrence (45 within 30 days, defined as early); the 4-year rate of VT recurrence or mortality or HTx was 70%. Independent predictors of mortality or HTx were early VT recurrence (HR: 2.92; 95% CI: 1.37-6.21; P < 0.01), amiodarone at discharge (HR: 3.23; 95% CI: 1.43-7.33; P < 0.01), renal dysfunction (HR: 1.92; 95% CI: 1.01-3.64; P = 0.046), and LVEF (HR: 1.36; 95% CI: 1.0-1.84; P = 0.052). LVEF ≤32% identified patients at risk for mortality or HTx (area under the curve: 0.75). Mortality or HTx per 100 person-years was 40.4 events after early, compared with 14.2 events after later VT recurrence and 8.5 events with no VT recurrence after RFCA (P < 0.01 for both). Patients with early recurrence and LVEFs ≤32% had a 1-year rate of mortality or HTx of 55%. VT recurrence was predicted by prior implantable cardioverter-defibrillator shocks, basal anteroseptal VT origin, and procedural failure but not LVEF. CONCLUSIONS: Patients with DCM needing RFCA for VT are a high-risk group. Following RFCA, approximately one-half remain free of VT recurrence. Early VT recurrence with LVEF ≤32% identifies those at very high risk for mortality or HTx, and screening for mechanical support or HTx should be considered. Late VT recurrence after RFCA does not predict worse outcome.

Predicting early reconnection after cryoballoon ablation with procedural and biophysical parameters.

BACKGROUND: Predicting early reconnection/dormant conduction (ERC) immediately after pulmonary vein isolation (PVI) can avoid a waiting period with adenosine testing. OBJECTIVE: To identify procedural and biophysical parameters predicting ERC. METHODS: Consecutive atrial fibrillation (AF) patients undergoing a first cryoballoon ablation (Arctic Front Advance) between 2014 and 2017 were included. ERC was defined as manifest or dormant pulmonary vein (PV) reconnection with adenosine 30 minutes after PVI. Time to isolation (TTI), balloon temperatures (BT), and thawing times were evaluated as potential predictors for ERC. Based on a multivariable model, cut-off-values were defined and a formula was constructed to be used in clinical practice. RESULTS: A total of 136 patients (60 ± 10 years, 96 male, 95% paroxysmal AF) were included. ERC was found in 40 (29%) patients (ERC group) and in 53 of 575 (9%) veins. Procedural and total ablation time and the number of unsuccessful freezes were significantly longer/higher in the ERC group compared to the non-ERC group (150 ± 40 vs 125 ± 34 minutes; 24 ± 5 vs 17 ± 4 minutes, and 38% vs 24%, respectively (P = .028). Multivariable analysis showed that a higher nadir balloon temperature (hazard ratio [HR] 1.17 [1.09-1.23, P < .001), a higher number of unsuccessful freezes (HR 1.69 [1.15-2.49], P = .008) and a longer TTI (HR 1.02 [1.01-1.03], P < .001) were independently associated with ERC, leading to the following formula: 0.02 × TTI + 0.5 × number of unsuccessful freezes + 0.2 × nadir BT with a cut-off value of ≤-6.7 to refrain from a waiting period with adenosine testing. CONCLUSION: Three easily available parameters were associated with ERC. Using these parameters during ablation can help to avoid a 30-minute waiting period and adenosine testing.

Myocardial calcification is associated with endocardial ablation failure of post-myocardial infarction ventricular tachycardia.

AIMS: In patients with post-myocardial infarction (post-MI) ventricular tachycardia (VT), the presence of myocardial calcification (MC) may prevent heating of a subepicardial VT substrate contributing to endocardial ablation failure. The aims of this study were to assess the prevalence of MC in patients with post-MI VT and evaluate the impact of MC on outcome after endocardial ablation. METHODS AND RESULTS: In 158 patients, the presence of MC was retrospectively assessed on fluoroscopy recordings in seven standard projections obtained during pre-procedural coronary angiograms. Myocardial calcification, defined as a distinct radiopaque area that moved synchronously with the cardiac contraction, was detected in 30 patients (19%). After endocardial ablation, only 6 patients (20%) with MC were rendered non-inducible compared with 56 (44%) without MC (P = 0.033) and of importance, 8 (27%) remained inducible for the clinical VT [compared with 9 (6%) patients without MC; P = 0.003] requiring therapy escalation. After a median follow-up of 31 months, 61 patients (39%) had VT recurrence and 47 (30%) died. Patients with MC had a lower survival free from the composite endpoint of VT recurrence or therapy escalation at 24-month follow-up (26% vs. 59%; P = 0.003). Presence of MC (HR 1.69; P = 0.046), a lower LV ejection fraction (HR 1.03 per 1% decrease; P = 0.017), and non-complete procedural success (HR 2.42; P = 0.002) were independently associated with a higher incidence of VT recurrence or therapy escalation. CONCLUSION: Myocardial calcification was present in 19% of post-MI patients referred for VT ablation and was associated with a high incidence of endocardial ablation failure.

The prognostic value of J-wave pattern for recurrence of ventricular tachycardia after catheter ablation in patients with myocardial infarction.

BACKGROUND: J-waves and fragmented QRS (fQRS) on surface ECGs have been associated with the occurrence of ventricular tachyarrhythmias. Whether these non-invasive parameters can also predict ventricular tachycardia (VT) recurrence after radiofrequency catheter ablation (RFCA) is unknown. Of interest, patients with a wide QRS-complex have been excluded from clinical studies on J-waves, although a J-wave like pattern has been described for wide QRS. METHODS: We retrospectively included 168 patients (67 ± 10 years; 146 men) who underwent RFCA of post-infarct VT. J-wave pattern were defined as J-point elevation ≥ 0.1 mV in at least two leads irrespective of QRS width. fQRS was defined as various RSR` pattern in patients with narrow QRS and more than two R wave in those with wide QRS. The primary endpoint was VT recurrence after RFCA up to 24 months. RESULTS: J-wave pattern and fQRS were present in 27 and 28 patients, respectively. Overlap of J-wave pattern and fQRS was observed in nine. During a median follow-up of 20 (interquartile range 9-24) months, 46 (27%) patients had VT recurrence. Kaplan-Meier curves revealed that both J-wave pattern and fQRS were associated with VT recurrence. Multivariate Cox regression analysis demonstrated that the presence of J-wave pattern (hazard ratio [HR] 2.84; 95% confidence interval [CI] 1.45-5.58; P = .002) and greater number of induced VT (HR 1.29; 95% CI 1.15-1.45; P < .001) were the independent predictors of VT recurrence. CONCLUSIONS: A J-wave pattern-but not fQRS-is independently associated with an increased risk of post-infarct VT recurrence after RFCA irrespective of QRS width. This simple non-invasive parameter may identify patients who require additional treatment.

Prevalence and Prognostic Impact of Pathogenic Variants in Patients With Dilated Cardiomyopathy Referred for Ventricular Tachycardia Ablation.

OBJECTIVES: This study aimed to assess the frequency of (likely) pathogenic variants (LP/Pv) among dilated cardiomyopathy (DCM) ventricular tachycardia (VT) patients referred for CA and their impact on procedural outcome and long-term prognosis. BACKGROUND: The prevalence of genetic variants associated with monomorphic VT among DCM is unknown. METHODS: Ninety-eight consecutive patients (age 56 ± 15 years; 84% men, left ventricular ejection fraction [LVEF] 39 ± 12%) referred for DCM-VT ablation were included. Patients underwent electroanatomical mapping and testing of ≥55 cardiomyopathy-related genes. Mapping data were analyzed for low-voltage areas and abnormal potentials. LP/Pv-positive (LP/Pv+) patients were compared with LP/Pv-negative (LP/Pv-) patients and followed for VT recurrence and mortality. RESULTS: In 37 (38%) patients, LP/Pv were identified, most frequently LMNA (n = 11 of 37, [30%]), TTN (n = 6 of 37, [16%]), PLN (n = 6 of 37, [16%]), SCN5A (n = 3 of 37, [8%]), RBM20 (n = 2 of 37, [5%]) and DSP (n = 2 of 37, [5%]). LP/Pv+ carriers had lower LVEF (35 ± 13% vs. LP/Pv-: 42 ± 11%; p = 0.005) and were less often men (n = 27 [73%] vs. n = 55 [90%]; p = 0.03). After a median follow-up of 2.4 years (interquartile range: 0.9 to 4.4 years), 63 (64%) patients had VT recurrence (LP/Pv+: 30 of 37 [81%] vs. LP/Pv-: 33 of 61 [54%]; p = 0.007). Twenty-eight patients (29%) died (LP/Pv+: 19 of 37 [51%] vs. LP/Pv-: 9 of 61 [15%]; p < 0.001). The cumulative 2-year VT-free survival was 41% in the total cohort (LP/Pv+: 16% vs. LP/Pv-: 54%; p = 0.001). The presence of LP/Pv (hazard ratio: 1.9; 95% confidence interval: 1.1 to 3.4; p = 0.02) and unipolar low-voltage area size/cm2 increase (hazard ratio: 2.5; 95% confidence interval: 1.6 to 4.0; p < 0.001) were associated with a decreased 2-year VT-free survival. CONCLUSIONS: In patients with DCM-VT, a genetic cause is frequently identified. LP/Pv+ patients have a lower LVEF and more extensive VT substrates, which, in combination with disease progression, may contribute to the poor prognosis. Genetic testing in patients with DCM-VT should therefore be recommended.

Entropy as a Novel Measure of Myocardial Tissue Heterogeneity for Prediction of Ventricular Arrhythmias and Mortality in Post-Infarct Patients.

OBJECTIVES: This study proposed entropy as a new late gadolinium enhanced cardiac magnetic resonance-derived parameter to evaluate tissue inhomogeneity, independent of signal intensity thresholds. This study hypothesized that entropy within the scar is associated with ventricular arrhythmias (VAs), whereas entropy of the entire left ventricular (LV) myocardium is associated with mortality. BACKGROUND: In patients after myocardial infarction, the heterogeneity of fibrosis determines the substrate for VA. Fibrosis in remote areas has been associated with heart failure and mortality. Late gadolinium-enhanced cardiac magnetic resonance has been used to delineate fibrosis, but available methods depend on signal intensity thresholds and results have been inconsistent. METHODS: Consecutive post-myocardial infarction patients undergoing late gadolinium enhanced cardiac magnetic resonance prior to implantable cardioverter-defibrillator implantation were included. From cardiac magnetic resonance imaging, total scar size, scar gray zone, scar transmurality, and tissue entropy were derived. Patients were followed for appropriate implantable cardioverter-defibrillator therapy and mortality. RESULTS: A total of 154 patients (age 64 ± 10 years, 84% male, LV ejection fraction 29 ± 10%, 47% acute revascularization) were included. During a median follow-up of 56 (interquartile range: 40 to 73) months, appropriate implantable cardioverter-defibrillator therapy occurred in 46 patients (30%), and 41 patients (27%) died. From multivariable analysis, higher entropy of the scar (hazard ratio [HR]: 1.9; 95% confidence interval [CI]: 1.0 to 3.5; p = 0.042) was independently associated with VA, after adjusting for multivessel disease, acute revascularization, LV ejection fraction, scar gray zone, and transmurality. Entropy of the entire LV was independently associated with mortality (HR: 3.2; 95% CI: 1.1 to 9.9; p = 0.038). CONCLUSIONS: High entropy within the scar was associated with VA and may indicate an arrhythmogenic scar. High entropy of the entire LV was associated with mortality and may reflect a fibrosis pattern associated with adverse remodeling.

Optimizing ablation duration using dormant conduction to reveal incomplete isolation with the second generation cryoballoon: A randomized controlled trial.

INTRODUCTION: Efficacy of cryoballoon ablation depends on balloon-tissue contact and ablation duration. Prolonged duration may increase extracardiac complications. The aim of this study is to determine the optimal additional ablation duration after acute pulmonary vein isolation (PVI). METHODS: Consecutive patients with paroxysmal AF were randomized to three groups according to additional ablation duration (90, 120, or 150 seconds) after acute PVI (time-to-isolation). Primary outcome was reconnection/dormant conduction (DC) after a 30 minutes waiting period. If present, additional 240 seconds ablations were performed. Ablations without time-to-isolation <90 seconds, esophageal temperature <18°C or decreased phrenic nerve capture were aborted. Patients were followed with 24-hour Holter monitoring at 3, 6, and 12 months. RESULTS: Seventy-five study patients (60 ± 11 years, 48 male) were included. Reconnection/DC per vein significantly decreased (22%, 6% and 4%) while aborted ablations remained stable (respectively 4, 5, and 7%) among the 90, 120, and 150 seconds groups. A shorter cryo-application time, longer time-to-isolation, higher balloon temperature and unsuccessful ablations predicted reconnection/DC. Freedom of atrial fibrillation was, respectively, 52, 56, and 72% in 90, 120, and 150 seconds groups ( P = 0.27), while repeated procedures significantly decreased from 36% to 4% ( P = 0.041) in the longer duration group compared to shorter duration group (150 seconds vs 90 seconds group). In multivariate Cox-regression only reconnection/DC predicted recurrence. CONCLUSION: Prolonging ablation duration after time-to-isolation significantly decreased reconnection/DC and repeated procedures, while recurrences and complications rates were similar. In a time-to-isolation approach, an additional ablation of 150 seconds ablation is the most appropriate.

Incidence and Clinical Significance of Cerebral Embolism During Atrial Fibrillation Ablation With Duty-Cycled Phased-Radiofrequency Versus Cooled-Radiofrequency: A Randomized Controlled Trial.

OBJECTIVES: The purpose of this study was to randomly compare the incidence of asymptomatic cerebral embolism (ACE) between the second-generation pulmonary vein ablation catheter (PVAC Gold) and the irrigated Thermocool catheter. BACKGROUND: Pulmonary vein isolation (PVI) with the PVAC is associated with ACE. The PVAC Gold was designed to avoid this complication. METHODS: Patients with paroxysmal atrial fibrillation were randomized 1:1 to PVI with the PVAC Gold or Thermocool catheter. Cerebral magnetic resonance imaging was performed in the days before and after ablation and repeated after 3 months in case of a new lesion. Monitoring for microembolic signals (MES) was performed by using transcranial Doppler ultrasonography. Parameters of coagulation were determined before, during, and after ablation. Neuropsychological tests and questionnaires were applied 10 days before and 3 months after ablation. RESULTS: Seventy patients were included in the study (mean age 61 ± 9 years; 43 male subjects; CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category] score 1.6 ± 1.2; international normalized ratio 2.7 ± 0.5; activated clotting time 374 ± 24 s; p > 0.05 for all parameters). Procedural duration was shorter in the PVAC Gold group (140 ± 34 vs. 207 ± 44 min; p < 0.001). Eight (23%; 7 infarcts) patients in the PVAC Gold group exhibited a new ACE, compared with 2 (6%; no infarcts) patients in the Thermocool group (p = 0.042). Median number of MES was higher in the PVAC Gold group (1,111 [interquartile range, 715-2,234] vs. 787 [interquartile range, 532-1,053]; p < 0.001). There were no differences between groups regarding coagulation and neuropsychological outcomes. CONCLUSIONS: PVI with the new PVAC Gold was associated with a higher incidence of ACE/cerebral infarcts and number of MES. Both catheters induced a comparable procoagulant state. Because there were no measurable differences in neuropsychological status, the clinical significance of ACE remains unclear. (Cerebral Embolism [CE] in Catheter Ablation of Atrial Fibrillation [AF] [CE-AF]; NCT01361295).

Mechanisms of sex differences in atrial fibrillation: role of hormones and differences in electrophysiology, structure, function, and remodelling.

Atrial fibrillation (AF) is the clinically most prevalent rhythm disorder with large impact on quality of life and increased risk for hospitalizations and mortality in both men and women. In recent years, knowledge regarding epidemiology, risk factors, and patho-physiological mechanisms of AF has greatly increased. Sex differences have been identified in the prevalence, clinical presentation, associated comorbidities, and therapy outcomes of AF. Although it is known that age-related prevalence of AF is lower in women than in men, women have worse and often atypical symptoms and worse quality of life as well as a higher risk for adverse events such as stroke and death associated with AF. In this review, we evaluate what is known about sex differences in AF mechanisms-covering structural, electrophysiological, and hormonal factors-and underscore areas of knowledge gaps for future studies. Increasing our understanding of mechanisms accounting for these sex differences in AF is important both for prognostic purposes and the optimization of (targeted, mechanism-based, and sex-specific) therapeutic approaches.

Targeting the Hidden Substrate Unmasked by Right Ventricular Extrastimulation Improves Ventricular Tachycardia Ablation Outcome After Myocardial Infarction.

OBJECTIVES: This study sought to determine whether ablation of hidden substrate unmasked by right ventricular extrastimulation (RVE) improves ablation outcome of post-myocardial infarction (MI) ventricular tachycardia (VT). BACKGROUND: In patients with small or nontransmural scars after MI, part of the VT substrate may be functional and, in addition, masked by high-voltage far-field signals arising from adjacent normal myocardium. METHODS: In 60 consecutive patients, systematic analysis of electrograms recorded from the presumed infarct area was performed during sinus rhythm, RV pacing at 500 ms, and during a short-coupled RV extrastimulus. Sites showing low-voltage, near-field potentials with evoked conduction delay in response to RVE were targeted. RESULTS: In 37 (62%) patients, ablation target sites located in areas with normal voltage during sinus rhythm were unmasked by RVE (hidden substrate group). These patients had better left ventricular function (36 ± 11% vs. 26 ± 12%; p = 0.003), smaller electroanatomical scars (<1.5 mV), and smaller dense scars (<0.5 mV) (median 59 and 14 cm2 vs. 82 and 44 cm2; p = 0.044 and p = 0.003) than did those in whom no hidden substrate was identified (overt substrate group). During a median follow-up of 16 months, 13 (22%) patients had VT recurrence. Patients with hidden substrate had a lower incidence of VT recurrence (12-month VT-free survival 89% vs. 50% in patients with overt substrate; p = 0.005). Compared with a historical cohort of 90 post-MI patients matched for left ventricular function and electroanatomical scar area, in whom no RVE was performed, patients in the hidden substrate group had a higher 1-year VT-free survival (89% vs. 73%; p = 0.039). CONCLUSIONS: Hidden substrate ablation unmasked by RVE improves ablation outcome in post-MI patients with small or nontransmural scars.

Programmed electrical stimulation-guided encircling cryoablation concomitant to surgical ventricular reconstruction for primary prevention of ventricular arrhythmias.

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.

Effect of Non-fluoroscopic Catheter Tracking on Radiation Exposure during Pulmonary Vein Isolation: Comparison of Four ablation systems.

BACKGROUND: A novel non-fluoroscopic catheter tracking system (Mediguide) can be used in combination with a 3D mapping system for atrial fibrillation (AF) ablation. However, the benefit on radiation exposure of the Mediguide system compared to other ablation systems is unknown. METHODS: We retrospectively enrolled consecutive 73 patients (51 men; 59±11 years; 60 paroxysmal AF) undergoing pulmonary vein isolation by the same operator. Radiation time, radiation effective dose, procedure time, AF recurrence after ablation, and procedure-related complications were compared among 4 different ablation systems. RESULTS: Mediguide was used in 16 patients (group A), CARTO™ in 17 (group B), Cryoballoon in 30 (group C), and Multi-electrode Pulmonary Vein Ablation Catheter (PVAC) in 10 (group D). Although procedure time was shorter in patients with Cryoballoon (median 110 [interquartile range 99-120] min) and PVAC (123 [112-146] min) compared to those with Mediguide (181 [168-214] min) and CARTO (179 [160-195] min) (P<0.001), radiation exposure time and effective dose were decreased in patients with Mediguide compared to the other ablation systems (A: 5 [3-6] min; B: 14 [11-16] min; C: 14 [11-18] min; D: 20 [16-24] min, P<0.001 and A: 1.1 [0.8-2.0] mSv; B: 2.5 [1.3-3.8] mSv; C: 2.0 [1.4-2.5] mSv; D: 1.7 [1.4-3.6] mSv, P=0.015, respectively). AF recurrence rates and procedure-related complications were comparable among the 4 groups. CONCLUSION: The Mediguide system reduces radiation exposure compared to other ablation systems without increasing AF recurrence or procedure-related complications.