J Interv Card Electrophysiol DOI 10.1007/s10840-015-0031-3
Abundant epicardial adipose tissue surrounding the left atrium predicts early rather than late recurrence of atrial fibrillation after catheter ablation Masaharu Masuda 1 & Hiroya Mizuno 1 & Yukihiro Enchi 2 & Hitoshi Minamiguchi 1 & Shozo Konishi 1 & Tomohito Ohtani 1 & Osamu Yamaguchi 1 & Yuji Okuyama 1 & Shinsuke Nanto 1 & Yasushi Sakata 1
Received: 4 February 2015 / Accepted: 15 June 2015 # Springer Science+Business Media New York 2015
Abstract Purpose Epicardial adipose tissue (EAT) surrounding the left atrium has been reported to have a pro-arrhythmic influence on atrial myocardium and to play an important role in the pathophysiology of atrial fibrillation (AF). The purpose of this study was to explore whether the abundance of EAT correlates with early and late recurrences of AF after ablation. Methods We included 53 consecutive patients with drugrefractory AF scheduled for ablation. Early and late recurrences were defined as atrial tachyarrhythmias within and after 3 months following the ablation procedure, respectively. The total and left atrial EAT volumes were obtained by 320detector-row multislice computed tomography. Results During a follow-up period of 16±4 months, early and late recurrences occurred in 29 (55 %) and 12 (23 %) patients, respectively. The left atrial EAT volume was larger in patients with than without early recurrence (35.1±13.1 vs. 25.0± 9.5 cm3, p=0.002); however, there was no difference in the total EAT volume between the two groups (98.5±45.7 vs. 94.5±35.2 cm3, p=0.72). A multivariate analysis revealed that a large left atrial EAT volume, persistent AF, and large left atrial volume were independent predictors of early recurrence. Conversely, there was no significant difference in left atrial (29.3±14.6 vs. 29.7±11.7 cm3, p=0.93) and total EAT
* Hiroya Mizuno [email protected] 1
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita-shi, Osaka 565-0871, Japan
2
Department of Medical Technology, Osaka University Hospital, 2-15, Yamadaoka, Suita-shi, Osaka 565-0871, Japan
(91.0±50.1 vs. 97.9±37.0 cm3, p=0.66) volumes between patients with and without late recurrence. Conclusions The abundance of left atrial EAT independently predicted early recurrence after AF ablation; on the contrary, it did not have an impact on late recurrence. Left atrial EAT may have a pro-arrhythmic influence, especially in the early postablation phase.
Keywords Atrial fibrillation . Ablation . Early recurrence . Epicardial adipose tissue
1 Introduction Epicardial adipose tissue (EAT) is a particular form of visceral adipose tissue that is in direct contact with the myocardium, and recent studies suggest that EAT has a proatherosclerotic effect and promotes the pathogenesis of coronary artery disease [1, 2]. Furthermore, several studies reported that patients with atrial fibrillation (AF) had abundant EAT surrounding the left atrium that could play an important role in the development and progression of AF by secreting pro-inflammatory and pro-fibrotic cytokines, such as tumor necrosis factor alpha, transforming growth factor beta, and interleukin-6 [1, 3, 4]. Catheter ablation has become an established treatment option for patients with AF with the recurrence rate of 10–30 %. The correlation between the left atrial EAT volume and AF recurrence after catheter ablation has been demonstrated in one clinical study [5]; however, it has not been fully elucidated. The purpose of this study was to explore whether the volume of EAT correlates with AF recurrences in the early and late phases among patients undergoing AF ablation.
J Interv Card Electrophysiol
2 Methods 2.1 Study patients From October 2012 to March 2014, consecutive patients who underwent an initial ablation of AF in our hospital were enrolled. Exclusion criteria were as follows: an age 80 bpm. The slice collimation was 320 × 0.50 mm. A bolus of nonionic iodinated contrast (Iomeron 350; Bracco, Singen, Germany) was injected through the antecubital vein at 0.075 ml/s/kg for 12 s, followed by a saline bolus chaser. The scan was started when the threshold of 200 Hounsfield units was reached in the ascending aorta. Cardiac images from the carina to the apex of the heart were acquired during one breath hold, with retrospective electrocardiographic gating. All data were processed using a workstation (Zio M900 Quadra; Amin, Tokyo, Japan). Image reconstruction for the EAT was performed at the end of the T wave on the electrocardiogram. The total EAT was measured by assigning Hounsfield units from −50 to −200 to adipose tissue. Thereafter, the left atrial EAT was manually segmented from the total EAT. It was obtained by eliminating the EAT from the left ventricular side anterior to the mitral annulus, right atrial side anterior to the right superior pulmonary vein, and lower side of the coronary sinus from the total EAT, leaving the EAT surrounding the left atrium. Figure 1 shows an example of the EAT measurement. In each patient, measurements of the total and left atrial EAT volumes were performed three times independently, and the mean of the three values was calculated. The intraobserver variability of the left atrial EAT volume was 3.8 %, and interobserver variability was 6.2 % from the measurements in 12 randomly selected patients. 2.3 Ablation procedure An electrophysiological study and ablation were performed under intravenous sedation using dexmedetomidine, with an initial injection of 3 μg/kg/h for 10 min followed by 0.2– 0.4 μg/kg/h during the procedure. A straight decapolar
catheter was placed between the superior vena cava and right atrium, and a deflectable 20-pole catheter was positioned in the coronary sinus. After a transseptal puncture at the fossa ovalis, direct visualization of all four pulmonary veins was performed using selective venography to show the venous anatomy and location of the left atrial–pulmonary vein junctions. A 20-pole circular catheter was placed at each pulmonary vein. Mapping and ablation were performed under guidance from an electroanatomical mapping system (CARTO 3; Biosense Webster, Diamond Bar, CA, USA). Then, the left atrial virtual geometry was traced manually using a SoundStar ICE catheter (Biosense Webster) and merged with the image from the reconstructed computed tomography. An irrigated ablation catheter with a 3.5-mm tip (NaviStar ThermoCool, Biosense Webster) was used for mapping and ablation. Radiofrequency energy was applied for 15–30 s at each site using a maximum temperature of 42 °C, a maximum power of 35 W, and a flow rate of 17 ml/min. An extensive encircling pulmonary vein isolation was performed. The procedural endpoint was the electrical isolation of all pulmonary veins from the left atrium. Following the pulmonary vein isolation, additional ablation was done to eliminate any residual atrial ectopy that initiated AF and to modify the atrial substrate maintaining AF or other atrial tachyarrhythmias at the discretion of the attending operator. Electrical cardioversion was performed when AF continued at the end of the ablation procedure. 2.4 Follow-up for AF recurrence After the ablation procedure, patients remained hospitalized for 2–3 days under continuous electrocardiography (ECG) monitoring. No antiarrhythmic drugs were prescribed unless repetitive recurrent AF developed. Then, patients were followed up for 3 months with a 2-week visit in a dedicated arrhythmia clinic at our institution. A standard 12-lead ECG was obtained at each outpatient visit, and 24-h ambulatory ECG monitoring (Holter) was performed at 2–3 months after ablation. When patients experienced symptoms suggestive of an arrhythmia, a surface ECG, ambulatory ECG, and/or cardiac event recording were additionally obtained. Any of the following events within and after 3 months post-ablation procedure were considered as early and late recurrences, respectively: (1) AF (or other atrial tachyarrhythmia) recorded on the standard or symptom-triggered 12-lead ECG during an outpatient visit or (2) AF of at least a 30-s duration on ambulatory ECG monitoring. Every patient was managed with a rhythm control strategy during follow-up, and recurrent AF was treated with antiarrhythmic drugs and/or electrical cardioversion. 2.5 Statistical analysis Continuous data are expressed as the mean±SD. Categorical data are presented as absolute values and percentages. Tests for
J Interv Card Electrophysiol Fig. 1 Measurement of the epicardial adipose tissue (EAT) volume. The green color indicates EAT. a, c The total EAT and left atrial EAT surrounding the left atrium, respectively. b, d The EAT subtracted from the left atrial tissue and chamber, respectively. The left atrial EAT was obtained by eliminating the EAT from the left ventricular side anterior to the mitral annulus, right atrial side anterior to the right superior pulmonary vein, and lower side of the coronary sinus from the whole-heart EAT, leaving the EAT surrounding the left atrium
significance were conducted using the unpaired t test or nonparametric test (Mann–Whitney U test) for continuous variables and the chi-square test or Fisher’s exact test for categorical variables. To assess correlations between the continuous variables, a Pearson’s correlation coefficient was calculated. A receiver operating characteristic (ROC) curve analysis was done to determine the best cutoff value of the left atrial EAT volume for the prediction of early recurrence. Survival rates free from AF recurrence were calculated using the Kaplan–Meier method. A log-rank test was used to compare the event-free survival curves between groups. Univariate and multivariate logistic regression analyses were used to determine the clinical factors that were associated with early recurrence. Variables with a p value ≤0.10 in Table 1 were included in the analysis. All analyses were performed using SPSS version 15.0 for Windows.
3 Results
Comparisons of the baseline and procedural characteristics between the patients with and without an early recurrence are shown in Table 1. There was no difference in the age, sex, body mass index, CHADS2 score, CHA2DS2-VASc score, and prescribed medications between the two groups. Patients with an early recurrence had persistent AF more frequently than those without. The left atrial volume was significantly larger and tended to be large in those with an early and late recurrence, respectively. Pulmonary vein isolation was successfully completed in all 53 patients. Additional ablation procedures were performed in nine patients as follows: cavotricuspid isthmus ablation for common flutter induced by atrial burst stimuli (six patients), left atrial roof ablation for induced roof-dependent flutter (two patients), and mitral isthmus ablation for induced peri-mitral flutter (two patients). Patients with early recurrences tended to need a longer radio-frequency energy application time than those without early recurrences. However, this correlation was not observed between patients with and without late recurrences.
3.1 Baseline and procedural characteristics Of the 58 consecutive patients that underwent an initial ablation for AF during the study period, 53 patients fulfilled the abovementioned criteria and were enrolled in this study. All 53 patients were followed up for a mean period of 16.0± 4.4 months, and the numbers of patients with early and late recurrences are presented in Fig. 2.
3.2 Association between the EAT volume and clinical background The associations between the EAT volumes and clinical backgrounds were examined. The total EAT volume demonstrated a significant positive, but not so strong, correlation with the body mass index (r2 =0.43, p
Abundant epicardial adipose tissue surrounding the left atrium predicts early rather than late recurrence of atrial fibrillation after catheter ablation Masaharu Masuda 1 & Hiroya Mizuno 1 & Yukihiro Enchi 2 & Hitoshi Minamiguchi 1 & Shozo Konishi 1 & Tomohito Ohtani 1 & Osamu Yamaguchi 1 & Yuji Okuyama 1 & Shinsuke Nanto 1 & Yasushi Sakata 1
Received: 4 February 2015 / Accepted: 15 June 2015 # Springer Science+Business Media New York 2015
Abstract Purpose Epicardial adipose tissue (EAT) surrounding the left atrium has been reported to have a pro-arrhythmic influence on atrial myocardium and to play an important role in the pathophysiology of atrial fibrillation (AF). The purpose of this study was to explore whether the abundance of EAT correlates with early and late recurrences of AF after ablation. Methods We included 53 consecutive patients with drugrefractory AF scheduled for ablation. Early and late recurrences were defined as atrial tachyarrhythmias within and after 3 months following the ablation procedure, respectively. The total and left atrial EAT volumes were obtained by 320detector-row multislice computed tomography. Results During a follow-up period of 16±4 months, early and late recurrences occurred in 29 (55 %) and 12 (23 %) patients, respectively. The left atrial EAT volume was larger in patients with than without early recurrence (35.1±13.1 vs. 25.0± 9.5 cm3, p=0.002); however, there was no difference in the total EAT volume between the two groups (98.5±45.7 vs. 94.5±35.2 cm3, p=0.72). A multivariate analysis revealed that a large left atrial EAT volume, persistent AF, and large left atrial volume were independent predictors of early recurrence. Conversely, there was no significant difference in left atrial (29.3±14.6 vs. 29.7±11.7 cm3, p=0.93) and total EAT
* Hiroya Mizuno [email protected] 1
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita-shi, Osaka 565-0871, Japan
2
Department of Medical Technology, Osaka University Hospital, 2-15, Yamadaoka, Suita-shi, Osaka 565-0871, Japan
(91.0±50.1 vs. 97.9±37.0 cm3, p=0.66) volumes between patients with and without late recurrence. Conclusions The abundance of left atrial EAT independently predicted early recurrence after AF ablation; on the contrary, it did not have an impact on late recurrence. Left atrial EAT may have a pro-arrhythmic influence, especially in the early postablation phase.
Keywords Atrial fibrillation . Ablation . Early recurrence . Epicardial adipose tissue
1 Introduction Epicardial adipose tissue (EAT) is a particular form of visceral adipose tissue that is in direct contact with the myocardium, and recent studies suggest that EAT has a proatherosclerotic effect and promotes the pathogenesis of coronary artery disease [1, 2]. Furthermore, several studies reported that patients with atrial fibrillation (AF) had abundant EAT surrounding the left atrium that could play an important role in the development and progression of AF by secreting pro-inflammatory and pro-fibrotic cytokines, such as tumor necrosis factor alpha, transforming growth factor beta, and interleukin-6 [1, 3, 4]. Catheter ablation has become an established treatment option for patients with AF with the recurrence rate of 10–30 %. The correlation between the left atrial EAT volume and AF recurrence after catheter ablation has been demonstrated in one clinical study [5]; however, it has not been fully elucidated. The purpose of this study was to explore whether the volume of EAT correlates with AF recurrences in the early and late phases among patients undergoing AF ablation.
J Interv Card Electrophysiol
2 Methods 2.1 Study patients From October 2012 to March 2014, consecutive patients who underwent an initial ablation of AF in our hospital were enrolled. Exclusion criteria were as follows: an age 80 bpm. The slice collimation was 320 × 0.50 mm. A bolus of nonionic iodinated contrast (Iomeron 350; Bracco, Singen, Germany) was injected through the antecubital vein at 0.075 ml/s/kg for 12 s, followed by a saline bolus chaser. The scan was started when the threshold of 200 Hounsfield units was reached in the ascending aorta. Cardiac images from the carina to the apex of the heart were acquired during one breath hold, with retrospective electrocardiographic gating. All data were processed using a workstation (Zio M900 Quadra; Amin, Tokyo, Japan). Image reconstruction for the EAT was performed at the end of the T wave on the electrocardiogram. The total EAT was measured by assigning Hounsfield units from −50 to −200 to adipose tissue. Thereafter, the left atrial EAT was manually segmented from the total EAT. It was obtained by eliminating the EAT from the left ventricular side anterior to the mitral annulus, right atrial side anterior to the right superior pulmonary vein, and lower side of the coronary sinus from the total EAT, leaving the EAT surrounding the left atrium. Figure 1 shows an example of the EAT measurement. In each patient, measurements of the total and left atrial EAT volumes were performed three times independently, and the mean of the three values was calculated. The intraobserver variability of the left atrial EAT volume was 3.8 %, and interobserver variability was 6.2 % from the measurements in 12 randomly selected patients. 2.3 Ablation procedure An electrophysiological study and ablation were performed under intravenous sedation using dexmedetomidine, with an initial injection of 3 μg/kg/h for 10 min followed by 0.2– 0.4 μg/kg/h during the procedure. A straight decapolar
catheter was placed between the superior vena cava and right atrium, and a deflectable 20-pole catheter was positioned in the coronary sinus. After a transseptal puncture at the fossa ovalis, direct visualization of all four pulmonary veins was performed using selective venography to show the venous anatomy and location of the left atrial–pulmonary vein junctions. A 20-pole circular catheter was placed at each pulmonary vein. Mapping and ablation were performed under guidance from an electroanatomical mapping system (CARTO 3; Biosense Webster, Diamond Bar, CA, USA). Then, the left atrial virtual geometry was traced manually using a SoundStar ICE catheter (Biosense Webster) and merged with the image from the reconstructed computed tomography. An irrigated ablation catheter with a 3.5-mm tip (NaviStar ThermoCool, Biosense Webster) was used for mapping and ablation. Radiofrequency energy was applied for 15–30 s at each site using a maximum temperature of 42 °C, a maximum power of 35 W, and a flow rate of 17 ml/min. An extensive encircling pulmonary vein isolation was performed. The procedural endpoint was the electrical isolation of all pulmonary veins from the left atrium. Following the pulmonary vein isolation, additional ablation was done to eliminate any residual atrial ectopy that initiated AF and to modify the atrial substrate maintaining AF or other atrial tachyarrhythmias at the discretion of the attending operator. Electrical cardioversion was performed when AF continued at the end of the ablation procedure. 2.4 Follow-up for AF recurrence After the ablation procedure, patients remained hospitalized for 2–3 days under continuous electrocardiography (ECG) monitoring. No antiarrhythmic drugs were prescribed unless repetitive recurrent AF developed. Then, patients were followed up for 3 months with a 2-week visit in a dedicated arrhythmia clinic at our institution. A standard 12-lead ECG was obtained at each outpatient visit, and 24-h ambulatory ECG monitoring (Holter) was performed at 2–3 months after ablation. When patients experienced symptoms suggestive of an arrhythmia, a surface ECG, ambulatory ECG, and/or cardiac event recording were additionally obtained. Any of the following events within and after 3 months post-ablation procedure were considered as early and late recurrences, respectively: (1) AF (or other atrial tachyarrhythmia) recorded on the standard or symptom-triggered 12-lead ECG during an outpatient visit or (2) AF of at least a 30-s duration on ambulatory ECG monitoring. Every patient was managed with a rhythm control strategy during follow-up, and recurrent AF was treated with antiarrhythmic drugs and/or electrical cardioversion. 2.5 Statistical analysis Continuous data are expressed as the mean±SD. Categorical data are presented as absolute values and percentages. Tests for
J Interv Card Electrophysiol Fig. 1 Measurement of the epicardial adipose tissue (EAT) volume. The green color indicates EAT. a, c The total EAT and left atrial EAT surrounding the left atrium, respectively. b, d The EAT subtracted from the left atrial tissue and chamber, respectively. The left atrial EAT was obtained by eliminating the EAT from the left ventricular side anterior to the mitral annulus, right atrial side anterior to the right superior pulmonary vein, and lower side of the coronary sinus from the whole-heart EAT, leaving the EAT surrounding the left atrium
significance were conducted using the unpaired t test or nonparametric test (Mann–Whitney U test) for continuous variables and the chi-square test or Fisher’s exact test for categorical variables. To assess correlations between the continuous variables, a Pearson’s correlation coefficient was calculated. A receiver operating characteristic (ROC) curve analysis was done to determine the best cutoff value of the left atrial EAT volume for the prediction of early recurrence. Survival rates free from AF recurrence were calculated using the Kaplan–Meier method. A log-rank test was used to compare the event-free survival curves between groups. Univariate and multivariate logistic regression analyses were used to determine the clinical factors that were associated with early recurrence. Variables with a p value ≤0.10 in Table 1 were included in the analysis. All analyses were performed using SPSS version 15.0 for Windows.
3 Results
Comparisons of the baseline and procedural characteristics between the patients with and without an early recurrence are shown in Table 1. There was no difference in the age, sex, body mass index, CHADS2 score, CHA2DS2-VASc score, and prescribed medications between the two groups. Patients with an early recurrence had persistent AF more frequently than those without. The left atrial volume was significantly larger and tended to be large in those with an early and late recurrence, respectively. Pulmonary vein isolation was successfully completed in all 53 patients. Additional ablation procedures were performed in nine patients as follows: cavotricuspid isthmus ablation for common flutter induced by atrial burst stimuli (six patients), left atrial roof ablation for induced roof-dependent flutter (two patients), and mitral isthmus ablation for induced peri-mitral flutter (two patients). Patients with early recurrences tended to need a longer radio-frequency energy application time than those without early recurrences. However, this correlation was not observed between patients with and without late recurrences.
3.1 Baseline and procedural characteristics Of the 58 consecutive patients that underwent an initial ablation for AF during the study period, 53 patients fulfilled the abovementioned criteria and were enrolled in this study. All 53 patients were followed up for a mean period of 16.0± 4.4 months, and the numbers of patients with early and late recurrences are presented in Fig. 2.
3.2 Association between the EAT volume and clinical background The associations between the EAT volumes and clinical backgrounds were examined. The total EAT volume demonstrated a significant positive, but not so strong, correlation with the body mass index (r2 =0.43, p
