Skin sympathetic nerve activity in different ablation settings for atrial fibrillation.

BACKGROUND: Modifying the autonomic system after catheter ablation may prevent the recurrence of atrial fibrillation (AF). Evaluation of skin sympathetic nerve activity (SKNA) is a noninvasive method for the assessment of sympathetic activity. However, there are few studies on the effects of different energy settings on SKNA. OBJECTIVE: To investigate the changes in SKNA in different energy settings and their relationship to AF ablation outcomes. METHODS: Seventy-two patients with paroxysmal and persistent AF were enrolled. Forty-three patients received AF ablation with the conventional (ConV) energy setting (low power for long duration), and 29 patients using a high-power, short-duration (HPSD) strategy. The SKNA was acquired from the right arm 1 day before and after the radiofrequency ablation. We analyzed the SKNA and ablation outcomes in the different energy settings. RESULTS: Both groups had a similar baseline average SKNA (aSKNA). We found that the median aSKNA increased significantly from 446.82 µV to 805.93 µV (p = 0.003) in the ConV group but not in the HPSD group. In the ConV group, patients without AF recurrence had higher aSKNA values. However, the 1-year AF recurrence rate remained similar between both groups (35 % vs. 28 %, p = 0.52). CONCLUSION: The post-ablation aSKNA levels increased significantly in the ConV group but did not change significantly in the HPSD group, which may reflect different neuromodulatory effects. However, the one-year AF recurrence rates were similar for both groups. These results demonstrate that the HPSD strategy has durable lesion creation but less lesion depth, which may reduce collateral damage.

Lower contact force predicts right pulmonary vein carina breakthrough after ablation index-guided pulmonary vein isolation using high-power short-duration.

INTRODUCTION: Carina breakthrough (CB) at the right pulmonary vein (RPV) can occur after circumferential pulmonary vein isolation (PVI) due to epicardial bridging or transient tissue edema. High-power short-duration (HPSD) ablation may increase the incidence of RPV CB. Currently, the surrogate of ablation parameters to predict RPV CB is not well established. This study investigated predictors of RPV CB in patients undergoing ablation index (AI)-guided PVI with HPSD. METHODS: The study included 62 patients with symptomatic atrial fibrillation (AF) who underwent AI-guided PVI using HPSD. Patients were categorized into two groups based on the presence or absence of RPV CB. Lesions adjacent to the RPV carina were assessed, and CB was confirmed through residual voltage, low voltage along the ablation lesions, and activation wavefront propagation. RESULTS: Out of the 62 patients, 21 (33.87%) experienced RPV CB (Group 1), while 41 (66.13%) achieved first-pass RPV isolation (Group 2). Despite similar AI and HPSD, patients with RPV CB had lower contact force (CF) at lesions adjacent to the RPV carina. Receiver operating characteristic (ROC) curve analysis identified CF < 10.5 g as a predictor of RPV CB, with 75.7% sensitivity and 56.2% specificity (area under the curve: 0.714). CONCLUSION: In patients undergoing AI-guided PVI with HPSD, lower CF adjacent to the carina was associated with a higher risk of RPV CB. These findings suggest that maintaining higher CF during ablation in this region may reduce the occurrence of RPV CB.

Comparison of Long-Term Clinical Outcomes Between Segmental and Circumferential Pulmonary Vein Isolation in Patients Undergoing Repeat Atrial Fibrillation Ablation.

BACKGROUND: Circumferential pulmonary vein isolation (CPVI) has supplanted segmental PVI (SPVI) as standard procedure for atrial fibrillation (AF). However, there is limited evidence examining the efficacy of these strategies in redo ablations. In this study, we investigated the difference in recurrence rates between SPVI and CPVI in redo ablations for PV reconnection.Methods and Results: This study retrospectively enrolled 543 patients who had undergone AF ablation between 2015 and 2017. Among them, 167 patients (30.8%, including 128 male patients and 100 patients with paroxysmal AF) underwent redo ablation for recurrent AF. Excluding 26 patients without PV reconnection, 141 patients [90 patients of SPVI (Group 1) and 51 patients of CPVI (Group 2)] were included. The AF-free survival rates were 53.3% and 56.9% in Group 1 and Group 2, respectively (P=0.700). The atrial flutter (AFL)-free survival rates were 90% and 100% in Group 1 and Group 2, respectively (P=0.036). The ablation time was similar between groups, and there no major complications were observed. CONCLUSIONS: For redo AF ablation procedures, SPVI and CPVI showed similar outcomes, except for a higher AFL recurrence rate for SPVI after long-term follow-up (>2 years). This may be due to a higher probability of residual PV gaps causing reentrant AFL.

Fractal complexity alternations in paroxysmal atrial fibrillation patients with and without recurrence after pulmonary vein isolation.

BACKGROUND: Pulmonary vein isolation (PVI) is a cornerstone therapy for paroxysmal atrial fibrillation (PAF). The variations in nonlinear heart rate variability (HRV) between patients with and without recurrences remain unclear. We aimed to characterize the nonlinear HRV before and after PVI in patients with and without recurrence. METHODS: Twenty-five drug-refractory PAF patients (56.0 ± 9.1 years old, 20 males) who received PVI were enrolled. Holter electrocardiography were performed before, 1-3, and 6-12 months after PVI. After 8.2 ± 2.5 months of follow-ups after PVI, patients were divided into two groups: the recurrence (n = 8) and non-recurrence (n = 17) groups. Linear and nonlinear HRV variables were analyzed, including the Poincaré Plot analysis and the Detrended Fluctuation Analysis (DFA). RESULTS: The non-recurrence group, but not the recurrence group, had decreased high-frequency component (HF), the root mean square of successive RR interval differences (RMSSD), and the Poincaré Plot index SD1 1-3 months after PVI and increased DFAslope2 6-12 months after PVI. The non-recurrence group's LF/HF ratio and DFAslope1 decreased significantly 1-3 and 6-12 months after PVI, respectively, whereas there was no significant change in the recurrence group after PVI. CONCLUSIONS: Significantly reduced vagal tone 1-3 months after PVI, increased long-term fractal complexity 6-12 months after PVI, and decreased sympathetic tone as well as short-term fractal complexity 1-3 and 6-12 months after PVI led to a better AF-free survival after PVI. These findings suggest that neuromodulation and heart rate dynamics play crucial roles in AF recurrence following PVI.

Levosimendan attenuates electrical alternans and prevents ventricular arrhythmia during therapeutic hypothermia in isolated rabbit hearts.

BACKGROUND: Therapeutic hypothermia (TH) increases the susceptibility to ventricular arrhythmias (VAs) by prolonging action potential duration (APD) and facilitating arrhythmogenic spatially discordant alternans (SDA). Levosimendan, a calcium sensitizer, has been reported to shorten APD by enhancing the adenosine triphosphate (ATP)-sensitive K current. OBJECTIVE: The purpose of this study was to test the hypothesis that, during TH, levosimendan shortens the already prolonged APD, attenuates SDA, and prevents VA. METHODS: Langendorff-perfused isolated rabbit hearts were subjected to TH (30°C) for 15 minutes, followed by treatment with either levosimendan 0.5 µM (n = 9) or vehicle (n = 8) for an additional 30 minutes under TH. Using an optical mapping system, epicardial APD was evaluated by S1 pacing. SDA threshold was defined as the longest pacing cycle length (PCL) that induces the phenomenon of SDA. Ventricular fibrillation (VF) inducibility was evaluated by burst pacing for 30 seconds at the shortest PCL that achieved 1:1 ventricular capture. RESULTS: During TH, levosimendan shortened ventricular APD (PCL 400 ms; from 259 ± 8 ms to 241 ± 18 ms; P = .036) and decreased SDA threshold (from 327 ± 88 ms to 311 ± 68 ms; P = .011). VF inducibility was lowered from 39% ± 30% to 14% ± 12% with levosimendan (P = .018), whereas APD at PCL 400 ms (P = .161), SDA threshold (P = 1), and VF inducibility (P = .173) were not changed by vehicle. CONCLUSION: During TH, levosimendan could protect hearts against VA by shortening APD and decreasing SDA threshold. Enhancing ATP-sensitive K current with levosimendan might be a novel approach to preventing VA during TH.

Post-ablation augmentation of skin sympathetic nerve activity predicts a poor outcome of idiopathic ventricular arrhythmias.

BACKGROUND: The neuromodulation effect after ventricular arrhythmia (VA) ablation is unclear. The study aimed to investigate skin sympathetic nerve activity (SKNA) changes in patients receiving catheter ablations for idiopathic VA. METHODS: Of 43 patients with drug-refractory symptomatic VA receiving ablation, SKNA was continuously recorded for 10 min during resting from electrocardiogram lead I configuration and bipolar electrodes on the right arm 1 day before and 1 day after ablation. RESULTS: Twenty-two patients with acute procedure success and no recurrence during follow-ups were classified as sustained success group (group 1). Other 21 patients were classified as failed ablation group (group 2). Baseline SKNA showed no significant difference between the two groups. Post-ablation SKNA in group 2 was significantly higher than in group 1. In patients with ablation involved right ventricular outflow tract (RVOT), the post-ablation SKNA was also significantly higher in group 2. In contrast, there was no difference in post-ablation SKNA between groups in patients receiving non-RVOT ablation. CONCLUSION: The neuromodulation response after RVOT ablation may correspond to the sympathetic nerve distribution at RVOT. Augmentation of sympathetic activity after VA ablation indicates an unsuccessful VA suppression, especially in patients receiving ablation of RVOT VA.

Impact of Amiodarone Therapy on the Ablation Outcome of Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy.

(1) Background: Catheter ablation (CA) is an accepted treatment option for drug-refractory ventricular tachycardia (VT) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). This study investigates the effect of amiodarone on ablation outcomes in ARVC. (2) Methods: The study enrolled patients with ARVC undergoing CA of sustained VT. In all patients, substrate modification was performed to achieve non-inducible VT. The patients were categorized into two groups according to whether they had used amiodarone before CA. Baseline and electrophysiological characteristics, substrate, and outcomes were compared. (3) Results: A total of 72 ARVC patients were studied, including 29 (40.3%) "off" amiodarone and 43 (56.7%) "on" amiodarone. The scar area was similar between the two groups. Patients "off" amiodarone had smaller endocardial and epicardial areas with abnormal electrograms. Twenty of 43 patients (47.5%) "on" amiodarone discontinued it within 3 months after CA. During a mean follow-up period of 43.2 ± 29.5 months, higher VT recurrence was observed in patients "on" amiodarone. Patients "on" amiodarone who discontinued amiodarone after CA had a lower recurrence than those without. (4) Conclusions: Patients with ARVC "on" amiodarone before CA had distinct substrate characteristics and worse ablation outcomes than patients "off" amiodarone, especially in those who had used amiodarone continuously.

Image and Speech Recognition Technology in the Development of an Elderly Care Robot: Practical Issues Review and Improvement Strategies.

As the world's population is aging and there is a shortage of sufficient caring manpower, the development of intelligent care robots is a feasible solution. At present, plenty of care robots have been developed, but humanized care robots that can suitably respond to the individual behaviors of elderly people, such as pose, expression, gaze, and speech are generally lacking. To achieve the interaction, the main objectives of this study are: (1) conducting a literature review and analyzing the status quo on the following four core tasks of image and speech recognition technology: human pose recognition, human facial expression recognition, eye gazing recognition, and Chinese speech recognition; (2) proposing improvement strategies for these tasks based on the results of the literature review. The results of the study on these improvement strategies will provide the basis for using human facial expression robots in elderly care.

Patterns and Characteristics of SKYLINE-Lumipoint Feature in the Catheter Ablation of Atypical Atrial Flutter: Insight from a Novel Lumipoint Module of Rhythmia Mapping System.

Background: Atypical atrial flutter (aAFL) is not uncommon, especially after a prior cardiac surgery or extensive ablation in atrial fibrillation (AF). Aims: To revisit aAFL, we used a novel Lumipoint algorithm in the Rhythmia mapping system to evaluate tachycardia circuit by the patterns of global activation histogram (GAH, SKYLINE) in assisting aAFL ablation. Methods: Fifteen patients presenting with 20 different incessant aAFL, including two naïve, six with a prior AF ablation, and seven with prior cardiac surgery were studied. Results: Reentry aAFL in SKYLINE typically was a multi-deflected peak with 1.5 GAH-valleys. Valleys were sharp and narrow-based. Most reentry aAFL (18/20, 90%) lacked a plateau and displayed a steep GAH-valley with 2 GAH-valleys per tachycardia. Each GAH-valley highlighted 1.9 areas in the map. Successful sites of ablation all matched one of the highlighted areas based on GAH-valleys < 0.4. These sites corresponded with the areas highlighted by GAH-score < 0.4 in reentry aAFL, and by GAH-score < 0.2 in localized-reentry aAFL. Conclusions: The present study showed benefits of the LumipointTM module applied to the RhythmiaTM mapping system. The results were the efficient detection of the slow conduction, better identification of ablation sites, and fast termination of the aAFL with favorable outcomes.

Risks of Ventricular Tachyarrhythmia and Mortality in Patients with Amyloidosis - A Long-Term Cohort Study.

Background: The presence of ventricular tachycardia (VT) is associated with higher mortality. The annual incidence of VT after a diagnosis of amyloidosis and the associated cardiovascular (CV) outcomes have not been well assessed in a large cohort. Methods: A total of 12,139 amyloidosis patients were identified from the Taiwan National Health Insurance Research Database. Non-amyloidosis group was matched 1:1 for age, gender, hypertension, and diabetes mellitus (DM) to the amyloidosis group using a propensity score. Analysis of the risk of CV outcomes was conducted. We also analyzed the incidence of cardiac amyloidosis (CA). Results: The incidence rates of amyloidosis and CA were 6.54 and 0.61 per 100,000 person-years, respectively. Multivariable analysis revealed that the risk of VT was higher in both the amyloidosis [hazard ratio (HR): 7.90; 95% confidence interval (CI): 4.49-13.9] and CA (HR: 153.3, 95% CI: 54.3-432.7) groups. In the amyloidosis group, the risk of heart failure (HF)-related hospitalization, CV death, and all-cause death was also higher. Amyloidosis was associated with a higher CV mortality rate following VT (HR: 1.50; 95% CI: 1.07-2.12). The onset of a new VT event in patients with amyloidosis was associated with HF, DM, chronic liver disease, and anti-arrhythmic drug use. Conclusions: In this nationwide cohort study, the incidence rates of amyloidosis and CA were 6.54 and 0.61 per 100,000 person-years, respectively. The long-term risks of VT and CV mortality were higher in the patients with amyloidosis and CA. The patients with amyloidosis had a poorer prognosis following VT events, highlighting the importance of continuous monitoring in these patients.

Efficacy of Cryoballoon Ablation for Atrial Fibrillation and Recurrence Predictors in an Asian Cohort.

BACKGROUND: Cryoballoon ablation (CBA) for atrial fibrillation (AF) is a rhythm control procedure used in clinical trials, mostly in Western countries. Its efficacy and the predictors of AF recurrence after CBA remain unclear for Asian populations. We aimed to investigate the efficacy of CBA and the predictors of AF recurrence after CBA in Asian AF patients. METHODS: We included consecutive AF patients undergoing CBA for rhythm control between 2014 and 2020. The baseline characteristics, including AF types, symptom severity, and left atrial diameter (LAD), were analyzed. Holter's monitoring and 12-lead ECG were performed to document AF recurrence. A multivariate Cox hazards regression model was used to evaluate the risk of AF recurrence. RESULTS: A total of 120 AF patients (aged 61.9 ± 9.3 years) were included. The percentage of patients free from AF in the year following CBA was 74.2%. Among the three independent predictors of AF recurrence within one year were the presence of persistent AF (p = 0.025), an LAD ≥ 4.75 cm (p = 0.016), and pre-procedural cardioversion (p = 0.025). All patients survived and none had a stroke after CBA. CONCLUSION: CBA for AF is an effective and safe procedure in Asian populations. The presence of persistent AF, an LAD ≥ 4.75 cm, and severe symptoms are predictors of AF recurrence in the year following CBA.

Rhythm Control Better Prevents Dementia than Rate Control Strategies in Patients with Atrial Fibrillation-A Nationwide Cohort Study.

Background: Atrial fibrillation (AF) increases the risk of dementia. Whether the pharmacological rhythm control of AF can reduce the risk of dementia compared to the rate control strategy remains unclear. We hypothesize that the rhythm control strategy is better than the rate control strategy in preventing dementia. Methods: AF patients aged ≥65 years were identified from the Taiwan National Health Insurance Database. Patients receiving anti-arrhythmic drugs at a cumulative defined daily dose (cDDD) of >30 within the first year of enrollment constituted the rhythm control group. Patients who used rate control medications for a cDDD of >30 constituted the rate control group. A multivariate Cox hazards regression model was used to determine the hazard ratio (HR) for dementia. Results: A total of 3382 AF patients (698 in the rhythm control group; 2684 in the rate control group) were analyzed. During a 4.86 ± 3.38 year follow-up period, 414 dementia events occurred. The rhythm control group had a lower rate of dementia than the rate control group (adjust HR: 0.75, p = 0.031). The rhythm control strategy reduced the risk of dementia particularly in those receiving aspirin (p = 0.03). Conclusions: In patients with AF, pharmacological rhythm control was associated with a lower risk of dementia than rate control over a long-term follow-up period, particularly in patients receiving aspirin treatment.

Hyperuricemia and diabetes mellitus when occurred together have higher risks than alone on all-cause mortality and end-stage renal disease in patients with chronic kidney disease.

INTRODUCTION: Hyperuricemia and diabetes mellitus (DM) are associated with increased mortality risk in patients with chronic kidney disease (CKD). Here we aimed to evaluate the independent and joint risks of these two conditions on mortality and end stage kidney disease (ESKD) in CKD-patients. METHODS: This retrospective cohort study enrolled 4380 outpatients (with CKD stage 3-5) with mortality and ESKD linkage during a 7-year period (from 2007 to 2013). All-causes mortality and ESKD risks were analyzed by multivariable-adjusted Cox proportional hazards models (adjusted for age, sex, smoke, previous coronary arterial disease, blood pressure, and medications for hyperlipidemia, hyperuricemia and renin-angiotensin system inhibitors). RESULTS: Overall, 40.5% of participants had DM and 66.4% had hyperuricemia. In total, 356 deaths and 932 ESKD events occurred during the 7 years follow-up. With the multivariate analysis, increased risks for all-cause mortality were: hyperuricemia alone, HR = 1.48 (1-2.19); DM alone, and HR = 1.52 (1.02-2.46); DM and hyperuricemia together, HR = 2.12 (1.41-3.19). Similar risks for ESKD were: hyperuricemia alone, HR = 1.34 (1.03-1.73); DM alone, HR = 1.59 (1.15-2.2); DM and hyperuricemia together, HR = 2.46 (1.87-3.22). CONCLUSIONS: DM and hyperuricemia are strongly associated with higher all-cause mortality and ESKD risk in patients with CKD stage 3-5. Hyperuricemia is similar to DM in terms of risk for all-cause mortality and ESKD. DM and hyperuricemia when occurred together further increase both risks of all-cause mortality and ESKD.

Detecting supraventricular tachycardia with smartwatches facilitates the decision for catheter ablation: A case series.

Smartwatch allows easy detection of arrhythmia. Such an approach is widely used for detecting atrial fibrillation. However, there has been no consensus on the diagnostic power of smartwatch-detected supraventricular tachycardia (SVT). We reported three patients of SVT presenting with infrequent palpitations. Their SVTs were not documented with single-lead or standard ECG in hospital before, but only recorded by the single-lead ECG on smartwatches. Electrophysiological studies confirmed the mechanisms of these SVTs and led to successful catheter ablations. In conclusion, in patients with recurrent symptomatic tachycardia and a smartwatch-detected SVT, an electrophysiological study is indicated rather than to wait for a standard ECG for clinical decision. This approach might prevent the delay for successful treatment.

The impact of height on recurrence after index catheter ablation of paroxysmal atrial fibrillation.

PURPOSE: The relationship between height and incident atrial fibrillation (AF) has recently been demonstrated. We aimed to evaluate the impact of height on outcomes of ablation in patients with drug-refractory symptomatic paroxysmal AF (PAF). METHODS: A total of 689 patients (470 males; age, 53.0 ± 11.7 years) with symptomatic paroxysmal AF receiving index catheter ablation (CA) between 2003 and 2013 were enrolled in this study. The baseline characteristics, ablation, and follow-up results were evaluated. The patients were categorized according to the quartiles of height for each sex. RESULTS: Patients in the lower quartiles of height had a lower incidence of AF recurrence (log-rank p = 0.022). Height in female patients was strongly associated with AF recurrence (p = 0.027) after an index ablation in the 6.33 ± 4.32 years of follow-up. Female patients > 159 cm in height had a higher likelihood of AF recurrence after index CA (HR = 2.01, 95% CI: 1.24-3.25, p = 0.005) than that in those below this height. In computed tomography (CT) scan, the superoinferior diameter of the left atrium (LA) correlated with body height in females, but not in male patients. CONCLUSIONS: Height is associated with AF recurrence after the index CA of PAF in female patients. In Asian populations, women above height 159 cm are twice as likely to have AF recurrence post-ablation as shorter women.

Long-term mortality and cardiovascular outcomes in patients with atrial flutter after catheter ablation.

AIMS: For patients with typical and atypical atrial flutter (AFL) but without history of atrial fibrillation (AF), the long-term cardiovascular (CV) outcomes after catheter ablation for AFL remain unclear. We compared the long-term all-cause mortality and CV outcomes in patients with AFL receiving catheter ablation compared with the results with medical therapy. METHODS AND RESULTS: Atrial flutter patients receiving catheter ablation for typical AFL were identified using the Health Insurance Database, and constituted the 'AFL ablation group'. Patients with typical and atypical AFL but without ablation (AFL without ablation group) were propensity matched to the AFL ablation group. Patients with prior AF diagnosis were excluded. Primary outcomes included all-cause and CV mortality, heart failure (HF) hospitalization, and stroke. The multivariable cox hazards regression model was used to evaluate the hazard ratio (HR) for study outcomes. A total of 3784 AFL patients (1892 patients in each group) was studied. Their mean follow-up durations were 7.85 ± 2.57 years (AFL without ablation group) and 8.31 ± 4.53 years (AFL ablation group). Atrial flutter with ablation patients had lower risks of all-cause mortality (HR: 0.68, P < 0.001), CV deaths (HR: 0.78, P = 0.001), HF hospitalization (HR: 0.84, P = 0.01), and stroke (HR: 0.80, P = 0.01). CONCLUSIONS: Catheter ablation for AFL in patients without prior AF was associated with lower risks of all-cause mortality and CV events compared with AFL patients without ablation during long-term follow-ups.

Novel model-based point scoring system for predicting stroke risk in atrial fibrillation patients: Results from a nationwide cohort study with validation.

BACKGROUND: The stroke risk scoring system for atrial fibrillation (AF) patients can vary considerably based on patients' status while receiving ablation. This study aimed to demonstrate a novel scoring system for stroke risk stratification based on the status of catheter ablation. METHODS: First, 787 patients with AF undergoing ablation were matched according to age, sex, and underlying diseases with the same number of patients not undergoing ablation using the propensity-score (PS)-matched cohort. Multivariate Cox model-derived coefficients were used to construct a simple point-based clinical model using the PS-matched cohort. Thereafter, the novel model (AF-CA-Stroke score) was validated in a nationwide AF cohort. RESULTS: The AF-CA-Stroke score was calculated based on age (point = 5), ablation status (point = 4), prior history of stroke (point = 4), chronic kidney disease (point = 2), diabetes mellitus (point = 1), and congestive heart failure (point = 1). Risk function to predict the 1-, 5-, 10-year absolute stroke risks was reported. The estimated area under the receive operating characteristic curve of the AF-CA-Stroke score in the PS-matched cohort was 0.845 (95% confidence interval: 0.824-0.865) to predict long-term stroke. A validation study showed that discrimination abilities in the AF-CA-Stroke scores were significantly higher than those in the CHADS2/CHA2DS2-VASc scores. The best cut-off value of the AF-CA-Stroke score to predict future strokes was ≥ 5. CONCLUSIONS: This novel model-based point scoring system effectively identifies stroke risk using clinical factors and AF ablation status of patients with AF. Various age stratifications and AF ablation should be considered in AF management.

Ventricular divergence correlates with epicardial wavebreaks and predicts ventricular arrhythmia in isolated rabbit hearts during therapeutic hypothermia.

INTRODUCTION: High beat-to-beat morphological variation (divergence) on the ventricular electrogram during programmed ventricular stimulation (PVS) is associated with increased risk of ventricular fibrillation (VF), with unclear mechanisms. We hypothesized that ventricular divergence is associated with epicardial wavebreaks during PVS, and that it predicts VF occurrence. METHOD AND RESULTS: Langendorff-perfused rabbit hearts (n = 10) underwent 30-min therapeutic hypothermia (TH, 30°C), followed by a 20-min treatment with rotigaptide (300 nM), a gap junction modifier. VF inducibility was tested using burst ventricular pacing at the shortest pacing cycle length achieving 1:1 ventricular capture. Pseudo-ECG (p-ECG) and epicardial activation maps were simultaneously recorded for divergence and wavebreaks analysis, respectively. A total of 112 optical and p-ECG recordings (62 at TH, 50 at TH treated with rotigaptide) were analyzed. Adding rotigaptide reduced ventricular divergence, from 0.13±0.10 at TH to 0.09±0.07 (p = 0.018). Similarly, rotigaptide reduced the number of epicardial wavebreaks, from 0.59±0.73 at TH to 0.30±0.49 (p = 0.036). VF inducibility decreased, from 48±31% at TH to 22±32% after rotigaptide infusion (p = 0.032). Linear regression models showed that ventricular divergence correlated with epicardial wavebreaks during TH (p<0.001). CONCLUSION: Ventricular divergence correlated with, and might be predictive of epicardial wavebreaks during PVS at TH. Rotigaptide decreased both the ventricular divergence and epicardial wavebreaks, and reduced the probability of pacing-induced VF during TH.