Europace Advance Access published May 21, 2015
CLINICAL RESEARCH
Europace doi:10.1093/europace/euv102
Predictors of left atrial volume index reduction following cryoballoon-based pulmonary vein isolation Muhammed Ulvi Yalcin 1, Kadri Murat Gurses2, Duygu Kocyigit 3*, Banu Evranos 3, Hikmet Yorgun 3, Levent Sahiner 3, Ergun Baris Kaya3, Mehmet Ali Oto3, Kudret Aytemir 3, and Necla Ozer 3 1 Department of Cardiology, Hakkari State Hospital, Hakkari, Turkey; 2Department of Cardiology, Kars Harakani State Hospital, Kars, Turkey; and 3Department of Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
Received 4 November 2014; accepted after revision 24 March 2015
Aims
Ablation for atrial fibrillation (AF) has been suggested to be associated with ‘reverse left atrial remodelling’. Reduction in left atrial volume index (LAVIR) is regarded as a determinant of reverse remodelling following pulmonary vein isolation (PVI). However, there is paucity on data about the predictors for LAVIR after PVI. In this study, we aimed to investigate predictors of LAVIR at 12 months in AF patients undergoing cryoballoon-based PVI. ..................................................................................................................................................................................... Methods Patients with symptomatic paroxysmal or persistent AF despite ≥1 antiarrhythmic drug(s), who were scheduled for cryoballoon-based AF ablation procedure per the recent consensus recommendations, were enrolled and followed-up for 12 and results months in this prospective observational study. Left atrial volume was derived using the biplane area–length method. A total of 160 patients (54.25 + 7.66 years, 44.40% female) were involved in the study. Reduction in left atrial volume index occurred in 120 patients. Age [hazard ratio (HR): 0.901, 95% confidence interval (CI): 0.828–0.981, P ¼ 0.017], hypertension (HR: 0.151, 95% CI: 0.048–0.471, P ¼ 0.001), mild mitral regurgitation (MR) (HR: 5.327, 95% CI: 1.489–19.058, P ¼ 0.010), and AF recurrence (HR: 0.017, 95% CI: 0.005–0.065, P , 0.001) were found to be independent predictors for LAVIR. ..................................................................................................................................................................................... Conclusion To the best of our knowledge, this is the largest study in the literature investigating the predictors of LAVIR following AF ablation. According to this data, younger patients without hypertension or moderate MR are most likely to experience LAVIR following ablation.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial fibrillation † Reverse remodelling † Left atrial volume index † Predictors
Introduction Catheter ablation has been established as a valuable therapeutic option in atrial fibrillation (AF) patients.1 It has been proposed that catheter ablation could have conflicting effects on left atrial (LA) size and function depending on the procedural outcome. After successful catheter ablation of AF, LA size has been reported to decrease, which is termed as ‘reverse LA remodeling’.2 In contrast, following catheter ablation with unfavourable outcomes, markedly different changes were observed.3 Left atrial volume index (LAVI) is a reliable measure of LA size which can be determined by transthoracic echocardiography. Reduction in LAVI (LAVIR) is regarded as a determinant of reverse
remodelling following pulmonary vein isolation (PVI). However, there is paucity on data about the predictors for LAVIR after PVI. Therefore, in this study we aimed to investigate predictors of LAVIR in AF patients undergoing cryoballoon-based PVI. We measured LAVI pre-procedurally and at 12-month follow-up.
Methods Study population Between September 2011 and July 2013, 160 patients with symptomatic paroxysmal or persistent AF despite ≥1 antiarrhythmic drug(s), who were scheduled for cryoballoon-based AF ablation procedure per the
* Corresponding author. Tel: +90 312 3051780; fax: +90 312 3114058, E-mail address: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
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What’s new? † Reduction in LAVI occurred in 75.0% of patients following PVI at 12 months. † Age, hypertension, and moderate MR are independent predictors of reduction in LAVI. † Patients with post-procedural AF recurrence have lower reduction in LAVI.
recent consensus recommendations, were enrolled in this prospective observational study.4 Exclusion criteria were poor image quality impeding tracing of LA volume, clinically significant valvular disease, congenital heart defects (e.g. atrial septal defect), left ventricular ejection fraction ,50%, LA diameter (LAD) .55 mm, and attempted catheter or surgical AF ablation in the past. Baseline demographic and clinical characteristics, including age, gender, body mass index (BMI), history of smoking, and alcohol consumption (≤1 drink/day for women and ≤2 drink/day for men, those with heavy drinking and alcohol abuse excluded), were collected for all patients. Data related to the diagnosis of AF including date of first diagnosis, history of stroke, and medications (anticoagulants, rate or rhythm control medications) were also recorded. Symptomatic severity of the patients was recorded according to the European Heart Rhythm Association score. Atrial fibrillation episodes that either lasted .7 days or required termination by cardioversion, either with drugs or by direct current cardioversion were defined as persistent; where AF episodes self-terminating within 7 days were defined as paroxysmal AF.1 The term ‘lone AF’ was used to describe AF patients who were under 60 years and had no history of cardiac disease or any risk factors for thromboembolism.1 All patients underwent transthoracic echocardiogram (TTE) and transoesophageal echocardiography to exclude left ventricular systolic dysfunction, valvular disease, and left atrial thrombus. Informed consent was taken from each patient before enrolment. The study was in compliance with the principles outlined in the Declaration of Helsinki and approved by the Institutional Ethics Committee.
Evaluation of left atrial dimension Each subject underwent a transthoracic two-dimensional (2D) guided M-mode echocardiogram using commercially available equipment (Vivid S6; GE Healthcare, Horten, Norway). All echocardiographic parameters were measured according to the recommendations of the American Society of Echocardiography5 by a single cardiologist blinded to the patient characteristics. Left atrial diameter was obtained in the parasternal long axis view. Left atrial area (LAA) and LA length were measured in the apical four-chamber and apical two-chamber views, respectively. Left atrial volume was derived using the biplane area– length method. Both LAA and LAV were measured at LV end-systole. Left atrial volume index was calculated based on the patient’s body surface area.5 Intra-observer variability testing for repeated LAV measurements from 25 subjects revealed an intra-class correlation coefficient of 0.943 (P , 0.001). Owing to this variability, LAVIR was defined as ≥5% reduction in LAVI following PVI.
M.U. Yalcin et al.
femoral vein and left femoral vein and artery punctures were performed with Seldinger technique. A 6 Fr steerable decapolar catheter (Dynamic DecaTM , Bard Electrophysiology) was placed in the coronary sinus. Single transseptal puncture by modified Brockenbrough technique (BRK-1TM , St Jude Medical) was performed under fluoroscopy and 8 Fr transseptal sheath (Biosense Webster) was placed into the LA. Once LA access was obtained, heparin boluses were repeatedly administered to maintain the activated clotting time between 300 and 350 s. The sheath was then exchanged for a 12 Fr steerable transseptal sheath (FlexCathTM , Medtronic CryoCath) over a guidewire (0.032 in., 180 cm Super StiffTM , St Jude Medical). During PVI with Arctic FrontTM (Medtronic CryoCath LP) (Arc-CB), baseline electrical potentials of all pulmonary veins (PVs) were recorded with a Lasso catheterTM (Biosense Webster, Inc.). On the other hand, in patients undergoing PVI with Arctic Front AdvanceTM (Medtronic Cryocath LP) (Arc-Adv-CB), the Achieve mapping catheterTM (Medtronic, Minneapolis, MN, USA) was used to document baseline PV potentials (PVPs). A 28-mm first generation CB catheter (Arc-CB) was used in 121 patients who underwent PVI between September 2011 and December 2012. A 28-mm second generation CB catheter (Arc-Adv-CB) was used in 39 patients who underwent PVI between December 2012 and July 2013. The cryoballoon was manoeuvred to all PV ostia by means of the steerable 12 Fr sheath and a guidewire inserted through the lumen of the balloon catheter. The balloon was inflated in the LA and then directed towards the PV ostia. Assessment of balloon occlusion was performed by injecting 50% diluted contrast through the cryoballoon catheter’s central lumen. Optimal vessel occlusion was considered to have been achieved when selective contrast injection showed total contrast retention with no flow back to the LA. Once occlusion was documented, cryothermal energy was started. A minimum of two consecutive freezing cycles were performed. The duration of each freezing cycle was 240 or 300 s. The procedure systematically began with the left superior PV, followed by the left inferior, right superior, and right inferior PVs. During ablation, if PVPs were visible during energy delivery, time to isolation was recorded when PVPs completely disappeared or were dissociated from LA activity. Acute procedural success was defined as elimination (or dissociation) of all PVPs.
Follow-up Following discharge from hospital, enrolled patients were scheduled for visits in the outpatient clinics at 1, 3, 6, and 12 months after ablation or earlier, if symptoms developed. At each visit, patients were evaluated for the recurrence of arrhythmias by means of physical examination, questioning for arrhythmia-related symptoms (palpitations, chest discomfort, fatigue, and dizziness), and a 12-lead ECG. A 24-h ambulatory Holter monitorization was conducted at 3, 6, and 12 months for all patients. Transthoracic echocardiogram, including LAV measurement and LAVI calculation, was performed at 12 months. The need for further oral anticoagulation was evaluated in the third month based on the CHA2DS2-VASc score. The outcome was assessed per the guidelines in the recent consensus document.4 A blanking period of 3 months was considered for the study. Any episode of AF, atrial flutter, or atrial tachycardia lasting at least 30 s and occurring in the blanking period was classified as an early recurrence. The same arrhythmias occurring after the blanking period were considered as late recurrences.
Statistical analysis Ablation procedure Ablation was performed under conscious sedation using boluses of midazolam. Invasive arterial blood pressure, oxygen saturation, and electrocardiogram (ECG) were monitored throughout the procedure. Right
Statistical analyses were performed using SPSS statistical software (version 21.0; SPSS Inc., Chicago, IL, USA). Normally distributed continuous parameters were presented as mean + standard deviation, where skewed continuous parameters were expressed as median (interquartile
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Predictors of left atrial volume index reduction
range, which was defined as minimum – maximum). Comparisons between baseline characteristics were performed by independent Student’s t, Mann– Whitney rank-sum, Fisher exact, or x 2 tests where appropriate. Cox proportional hazards regression for survival from AF recurrence was performed to identify predictors of recurrence; whereas univariate and multivariate linear regression analyses were performed to identify predictors of change in LAV following PVI. A twotailed P , 0.05 was considered statistically significant.
Table 1 The baseline demographic, clinical and echocardiographic parameters of the study population (n 5 160) Demographic parameters Gender: female (%) Age (years)
71 (44.40) 54.25 + 7.66
Clinical parameters
Results
BMI (kg/m2) Hypertension, n (%)
24.98 + 2.91 64 (40.00)
Patient characteristics and ablation procedure
Diabetes mellitus, n (%)
24 (15.00)
Coronary artery disease, n (%) Hyperlipidaemia, n (%)
20 (12.50) 40 (25.00)
A total of 160 patients (54.25 + 7.66 years, 44.40% female) were involved in the study. One hundred and eighteen patients (73.80%) had paroxysmal AF, whereas 42 patients (26.30%) had persistent AF (Table 1). Baseline characteristics of the study population are shown in Table 1. A total of 657 PVs were attempted for PVI. No patient was excluded due to anatomical reasons based on the computed tomography (CT) scan. Pulmonary vein isolation was performed by using either Arc-CB (n ¼ 121) or Arc-Adv-CB (n ¼ 39). Acute procedural success rate was 652/657 (99.23%). The five intact PVs were the right inferior PVs in patients who developed phrenic nerve palsy during isolation of right superior PVs.
Follow-up Patients were followed-up for 12 months. During the follow-up period, 124 of 160 patients (77.50%) were free of AF recurrence based on the aforementioned follow-up evaluation criteria. Cox proportional hazards regression analysis for survival from AF recurrence following ablation has revealed that LAVI was the only independent predictor (Table 2).
Predictors for reduction in left atrial volume index Baseline and follow-up characteristics of patients regarding the presence of LAVIR are shown in Table 3. Reduction in LAVI occurred in 120 patients. Left atrial volume index was significantly higher in patients without LAVI reduction when compared to those with LAVI reduction (34.00 + 4.00 vs. 30.15 + 2.40 mL/m2, P , 0.001). Patients without LAVIR were significantly older (56.93 + 5.24 vs. 53.36 + 8.14 years, P ¼ 0.002), had higher prevalence of hypertension (72.50 vs. 29.17%, P , 0.001), moderate mitral regurgitation (MR) (35.00 vs. 18.33%, P ¼ 0.049), and longer duration of AF [36 (18–100) vs. 36 (12–120) months, P ¼ 0.027]. Prevalence of persistent AF was higher (47.50 vs. 19.17%, P ¼ 0.001), whereas lone AF prevalence was lower (12.50 vs. 30.00%, P ¼ 0.047) in these patients. In addition, the rate of recurrence at 12 months was higher in patients without LAVIR (67.50 vs. 7.50%, P , 0.001) (Table 3). Linear regression analyses were performed to identify parameters independently associated with LAVIR following cryoballoon-based PVI for AF. Multivariate linear regression analysis is shown in Table 4. Age [hazard ratio (HR): 0.901, 95% confidence interval (CI): 0.828 –0.981, P ¼ 0.017], hypertension (HR: 0.151, 95% CI: 0.048–0.471, P ¼ 0.001), mild MR (HR: 5.327, 95% CI: 1.489 – 19.058, P ¼ 0.010), and AF recurrence (HR: 0.017, 95% CI: 0.005 –
Smoking, n (%)
53 (33.10)
Alcohol consumption, n (%) Duration of AF (months)
11 (6.90) 36 (12–120)
Type of AF, n (%) Paroxysmal AF Persistent AF
118 (73.80) 42 (26.30)
Lone AF
41 (25.60)
EHRA score (1– 4) 1
3 (2–4) 0
2
80 (50.00)
3 4
70 (43.80) 10 (6.30)
Number of antiarrhythmic drugs per patient (n) 1 2
70 (43.80) 76 (47.50)
3
14 (8.80)
ACEi/ARB use, n (%) Statin use, n (%)
58 (36.25) 32 (20.00)
Echocardiographic parameters LAD (mm) LAVI (mL/m2)
37.76 + 3.36 31.06 + 3.27
LV end-diastolic diameter (mm)
47.41 + 3.47
LV end-systolic diameter (mm) LV ejection fraction (%)
31.00 + 2.92 64.00 + 3.00
Mitral regurgitation Mild, n (%) Moderate, n (%)
124 (77.50) 36 (22.50)
Severe, n (%)
0
ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; AF, atrial fibrillation; BMI, body mass index; EHRA, European Heart Rhythm Association; LAD, left atrial diameter; LAVI, left atrium volume index; LV, left ventricular.
0.065, P , 0.001) were found to be independently associated with LAVIR (Table 4).
Discussion Up to now, there is paucity of data evaluating predictors of LAVIR following cryoballoon-based AF ablation. In this study, we have demonstrated that age, hypertension, severity of pre-procedural MR, and post-procedural AF recurrence are independent predictors of
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M.U. Yalcin et al.
Table 2 Cox regression analysis for identifying independent predictors of atrial fibrillation recurrence following ablation Variables
Univariate Cox regression analysis
Multivariate Cox regression analysis
HR (95% CI)
HR (95% CI)
................................................... P-Value
................................................... P-Value
............................................................................................................................................................................... Age (years)
1.030 (0.985–1.077)
0.197
1.007 (0.963–1.053)
0.765
Gender: male (%)
0.806 (0.421–1.543)
0.516
–
–
BMI (kg/m2) Hypertension (%)
1.052 (0.960–1.152) 1.152 (0.617–2.150)
0.275 0.657
– –
– –
Diabetes mellitus (%)
1.207 (0.533–2.733)
0.652
–
–
Coronary artery disease (%)
0.945 (0.395–2.263)
0.899
–
–
Smoking (%) Alcohol consumption (%)
1.173 (0.623–2.210) 0.957 (0.294–3.114)
0.621 0.942
– –
– –
Type of AF: persistent (%)
1.589 (0.842–2.994)
0.153
1.044 (0.495–2.204)
0.909
Duration of AF (months) LVEDD (mm)
1.001 (0.990–1.012) 1.104 (0.997–1.222)
0.818 0.058
– 1.058 (0.964–1.161)
– 0.237
LVEF (%)
0.976 (0.890–1.070)
0.601
LAVI (mL/m2) Mitral regurgitation: moderate (%)
1.337 (1.243–1.439) 1.272 (0.621–2.604)
,0.001* 0.510
– 1.345 (1.246–1.451) –
– ,0.001* –
AF, atrial fibrillation; BMI, body mass index; CI, confidence interval; HR, hazard ratio; LAVI, left atrial volume index; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction. *P , 0.05.
Table 3 Baseline and follow-up characteristics of the study population regarding the presence of LAVIR Variables
LAVIR
............................................................ 1 (n 5 120)
P-Value
– (n 5 40)
............................................................................................................................................................................... Demographic parameters Gender: female (%) Age (years) Clinical parameters
54 (45.00)
17 (42.50)
0.927
53.36 + 8.14
56.93 + 5.24
0.002*
BMI (kg/m2)
24.84 + 2.97
25.40 + 2.72
Hypertension, n (%) Diabetes mellitus, n (%)
35 (29.17) 15 (12.50)
29 (72.50) 9 (22.50)
,0.001* 0.201
Hyperlipidaemia, n (%)
28 (23.33)
12 (30.00)
0.527
Coronary artery disease, n (%) Smoking, n (%)
13 (10.83) 39 (32.50)
7 (17.50) 14 (35.00)
0.408 0.923
0.297
Alcohol consumption, n (%)
8 (6.67)
3 (7.50)
0.960
Duration of AF (months) Type of AF: persistent, n (%)
36 (12–120) 23 (19.17)
36 (18– 100) 19 (47.50)
0.027* 0.001*
Lone AF, n (%)
36 (30.00)
5 (12.50)
0.047*
ACEi/ARB use, n (%) Statin use, n (%)
44 (36.67) 25 (20.83)
14 (35.00) 7 (17,50)
0.934 0.714
LAVI (mL/m2) LV end-diastolic diameter (mm)
30.15 + 2.40 47.24 + 3.51
34.00 + 4.00 48.00 + 3.32
LV end-systolic diameter (mm)
30.52 + 2.85
31.45 + 3.07
0.107
LV ejection fraction (%) Mitral regurgitation: moderate, n (%)
65.39 + 3.14 22 (18.33)
64.48 + 3.36 14 (35.00)
0.059 0.049*
9 (7.50)
27 (67.50)
Echocardiographic parameters ,0.001* 0.214
Follow-up parameters Recurrence, n (%)
,0.001*
ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; AF, atrial fibrillation; BMI, body mass index; LAVI, left atrial volume index; LAVIR, reduction in LAVI; LV, left ventricular. *P , 0.05.
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Predictors of left atrial volume index reduction
Table 4 Multivariate linear regression analysis for identifying independent predictors of LAVIR Variables
Multivariate linear regression analysis
.........................................
HR (95% CI)
P-Value
................................................................................ Age (years) Hypertension (%)
0.901 (0.828– 0.981) 0.151 (0.048– 0.471)
0.017* 0.001*
Paroxysmal AF (%)
2.838 (0.818– 9.847)
0.100
Lone AF (%) Duration of AF (months)
1.802 (0.317– 10.241) 1.019 (0.991– 1.048)
0.506 0.177
LAVI (mL/m )
0.925 (0.714– 1.198)
0.552
Mild mitral regurgitation (%) Recurrence (%)
5.327 (1.489– 19.058) 0.017 (0.005– 0.065)
0.010* ,0.001*
2
AF, atrial fibrillation; CI, confidence interval; LAVI, left atrial volume index; LAVIR, reduction in LAVI. *P , 0.05.
LAVIR following cryoballoon-based PVI for AF. To the best of our knowledge, this is the largest study in the literature investigating the predictors of LAVIR following AF ablation. In a previous study, LA diameter has been reported to be one of the parameters that has a predictive role in AF ablation outcomes.6 Successful catheter ablation has been shown to result in reverse LA remodelling.7,8 On the other hand, a meta-analysis has demonstrated that LAVI may show an increase in patients developing AF recurrence.3 The single study in the literature that is focused on predictors of LAVIR has reported that lone AF, hypertension, and ablation success are independent predictors for LAVIR.9 An increase in interstitial atrial fibrosis, which contributes to abnormal LA compliance, is known to occur as a part of the normal aging process.10 A reverse correlation between age and LA reverse remodelling has been reported in the previous study.11 Since irreversible changes, including extent of fibrosis and hypertrophy, increase with age, LA elasticity is reduced and LA remodelling is less probable even if volume overload is released by several interventions. In our study, age significantly reduced the possibility of LAVIR (HR: 0.901, P ¼ 0.017) following cryoballoon-based PVI compatible with the previous findings. In a previous study, LA diastolic stiffness was shown to be regulated by BMI, systolic blood pressure (SBP), and LV systolic function in patients with normal-sized LA; and by age, LAVI, and LV diastolic and systolic function in patients with enlarged LA.12 This finding is remarkable for showing that high SBP may have an adverse impact on LA structural remodelling even when dilatation has not occurred. Activated renin–angiotensin system and secondary elevation in afterload may have an influence on the atrial remodelling process in arterial hypertension.13 Our study has also shown that hypertension significantly reduced the possibility of LAVIR (HR: 0.151, P ¼ 0.001) following cryoballoon-based PVI. Volume overload in chronic severe MR has been demonstrated to cause LA remodelling. This has been suggested to be related with cellular hypertrophy and interstitial fibrosis that occur in the LA to compensate volume overload in order to prevent pulmonary
congestion.14,15 In several studies, LA reverse remodelling has been reported following mitral valve surgery or percutaneous valve intervention.16 Greater reverse remodelling has been observed with a greater degree of MR reduction.17 We did not include patients with severe MR in our study. Therefore, multivariate linear regression analysis was performed by comparing moderate with mild MR. Patients with mild MR had higher possibility of LAVIR when compared with those with moderate MR (HR: 5.327, P ¼ 0.010) in our study in accordance with the previous studies’ findings.
Study limitations We used 2D TTE to measure LAV, although performing measurements with magnetic resonance imaging or multislice CT could have been more accurate.
Conclusion Our study has shown that age, hypertension, and severity of MR are independent predictors of LAVIR following cryoballoon-based PVI. In addition, successful AF ablation was independently associated with LAVIR. Clinical implications of these findings need to be evaluated further in larger study populations. Conflict of interest: none declared.
References 1. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation— developed with the special contribution of the European Heart Rhythm Association. Europace 2012;14:1385 –413. 2. Jayam VK, Dong J, Vasamreddy CR, Lickfett L, Kato R, Dickfeld T et al. Atrial volume reduction following catheter ablation of atrial fibrillation and relation to reduction in pulmonary vein size: an evaluation using magnetic resonance angiography. J Interv Card Electrophysiol 2005;13:107 –14. 3. Jeevanantham V, Ntim W, Navaneethan SD, Shah S, Johnson AC, Hall B et al. Meta-analysis of the effect of radiofrequency catheter ablation on left atrial size, volumes and function in patients with atrial fibrillation. Am J Cardiol 2010;105: 1317 –26. 4. Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA et al. 2012 HRS/ EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. Europace 2012;14:528 – 606. 5. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440 –63. 6. Abecasis J, Dourado R, Ferreira A, Saraiva C, Cavaco D, Santos KR et al. Left atrial volume calculated by multi-detector computed tomography may predict successful pulmonary vein isolation in catheter ablation of atrial fibrillation. Europace 2009;11:1289–94. 7. Reant P, Lafitte S, Jais P, Serri K, Weerasooriya R, Hocini M et al. Reverse remodeling of the left cardiac chambers after catheter ablation after 1 year in a series of patients with isolated atrial fibrillation. Circulation 2005;112:2896 –903. 8. Hof IE, Vonken EJ, Velthuis BK, Wittkampf FH, van der Heijden JF, Neven KG et al. Impact of pulmonary vein antrum isolation on left atrial size and function in patients with atrial fibrillation. J Interv Card Electrophysiol 2014;39:201–9. 9. Fredersdorf S, Ucer E, Jungbauer C, Dornia C, Eglmeier J, Eissnert C et al. Lone atrial fibrillation as a positive predictor of left atrial volume reduction following ablation of atrial fibrillation. Europace 2014;16:26 –32. 10. Hayashi H, Wang C, Miyauchi Y, Omichi C, Pak HN, Zhou S et al. Aging-related increase to inducible atrial fibrillation in the rat model. J Cardiovasc Electrophysiol 2002;13:801 –8.
Page 6 of 6 11. Hyllen S, Nozohoor S, Meurling C, Wierup P, Sjogren J. Determinants of left atrial reverse remodeling after valve surgery for degenerative mitral regurgitation. J Heart Valve Dis 2013;22:2– 10. 12. Miyoshi H, Oishi Y, Mizuguchi Y, Iuchi A, Nagase N, Ara N et al. Association of left atrial reservoir function with left atrial structural remodeling related to left ventricular dysfunction in asymptomatic patients with hypertension: evaluation by two-dimensional speckle-tracking echocardiography. Clin Exp Hypertens 2015;37:155–65. 13. Kim SJ, Choisy SC, Barman P, Zhang H, Hancox JC, Jones SA et al. Atrial remodeling and the substrate for atrial fibrillation in rat hearts with elevated afterload. Circ Arrhythm Electrophysiol 2011;4:761–9. 14. Braunwald E, Awe WC. The syndrome of severe mitral regurgitation with normal left atrial pressure. Circulation 1963;27:29 –35.
M.U. Yalcin et al.
15. Anne W, Willems R, Roskams T, Sergeant P, Herijgers P, Holemans P et al. Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation. Cardiovasc Res 2005;67:655 –66. 16. Le Bihan DC, Della Togna DJ, Barretto RB, Assef JE, Machado LR, Ramos AI et al. Early improvement in left atrial remodeling and function after mitral valve repair or replacement in organic symptomatic mitral regurgitation assessed by threedimensional echocardiography. Echocardiography 2014. [Epub ahead of print: doi: 10.1111/echo.12817]. 17. Grayburn PA, Foster E, Sangli C, Weissman NJ, Massaro J, Glower DG et al. Relationship between the magnitude of reduction in mitral regurgitation severity and left ventricular and left atrial reverse remodeling after MitraClip therapy. Circulation 2013; 128:1667 –74.
CLINICAL RESEARCH
Europace doi:10.1093/europace/euv102
Predictors of left atrial volume index reduction following cryoballoon-based pulmonary vein isolation Muhammed Ulvi Yalcin 1, Kadri Murat Gurses2, Duygu Kocyigit 3*, Banu Evranos 3, Hikmet Yorgun 3, Levent Sahiner 3, Ergun Baris Kaya3, Mehmet Ali Oto3, Kudret Aytemir 3, and Necla Ozer 3 1 Department of Cardiology, Hakkari State Hospital, Hakkari, Turkey; 2Department of Cardiology, Kars Harakani State Hospital, Kars, Turkey; and 3Department of Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
Received 4 November 2014; accepted after revision 24 March 2015
Aims
Ablation for atrial fibrillation (AF) has been suggested to be associated with ‘reverse left atrial remodelling’. Reduction in left atrial volume index (LAVIR) is regarded as a determinant of reverse remodelling following pulmonary vein isolation (PVI). However, there is paucity on data about the predictors for LAVIR after PVI. In this study, we aimed to investigate predictors of LAVIR at 12 months in AF patients undergoing cryoballoon-based PVI. ..................................................................................................................................................................................... Methods Patients with symptomatic paroxysmal or persistent AF despite ≥1 antiarrhythmic drug(s), who were scheduled for cryoballoon-based AF ablation procedure per the recent consensus recommendations, were enrolled and followed-up for 12 and results months in this prospective observational study. Left atrial volume was derived using the biplane area–length method. A total of 160 patients (54.25 + 7.66 years, 44.40% female) were involved in the study. Reduction in left atrial volume index occurred in 120 patients. Age [hazard ratio (HR): 0.901, 95% confidence interval (CI): 0.828–0.981, P ¼ 0.017], hypertension (HR: 0.151, 95% CI: 0.048–0.471, P ¼ 0.001), mild mitral regurgitation (MR) (HR: 5.327, 95% CI: 1.489–19.058, P ¼ 0.010), and AF recurrence (HR: 0.017, 95% CI: 0.005–0.065, P , 0.001) were found to be independent predictors for LAVIR. ..................................................................................................................................................................................... Conclusion To the best of our knowledge, this is the largest study in the literature investigating the predictors of LAVIR following AF ablation. According to this data, younger patients without hypertension or moderate MR are most likely to experience LAVIR following ablation.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Atrial fibrillation † Reverse remodelling † Left atrial volume index † Predictors
Introduction Catheter ablation has been established as a valuable therapeutic option in atrial fibrillation (AF) patients.1 It has been proposed that catheter ablation could have conflicting effects on left atrial (LA) size and function depending on the procedural outcome. After successful catheter ablation of AF, LA size has been reported to decrease, which is termed as ‘reverse LA remodeling’.2 In contrast, following catheter ablation with unfavourable outcomes, markedly different changes were observed.3 Left atrial volume index (LAVI) is a reliable measure of LA size which can be determined by transthoracic echocardiography. Reduction in LAVI (LAVIR) is regarded as a determinant of reverse
remodelling following pulmonary vein isolation (PVI). However, there is paucity on data about the predictors for LAVIR after PVI. Therefore, in this study we aimed to investigate predictors of LAVIR in AF patients undergoing cryoballoon-based PVI. We measured LAVI pre-procedurally and at 12-month follow-up.
Methods Study population Between September 2011 and July 2013, 160 patients with symptomatic paroxysmal or persistent AF despite ≥1 antiarrhythmic drug(s), who were scheduled for cryoballoon-based AF ablation procedure per the
* Corresponding author. Tel: +90 312 3051780; fax: +90 312 3114058, E-mail address: [email protected] Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: [email protected].
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What’s new? † Reduction in LAVI occurred in 75.0% of patients following PVI at 12 months. † Age, hypertension, and moderate MR are independent predictors of reduction in LAVI. † Patients with post-procedural AF recurrence have lower reduction in LAVI.
recent consensus recommendations, were enrolled in this prospective observational study.4 Exclusion criteria were poor image quality impeding tracing of LA volume, clinically significant valvular disease, congenital heart defects (e.g. atrial septal defect), left ventricular ejection fraction ,50%, LA diameter (LAD) .55 mm, and attempted catheter or surgical AF ablation in the past. Baseline demographic and clinical characteristics, including age, gender, body mass index (BMI), history of smoking, and alcohol consumption (≤1 drink/day for women and ≤2 drink/day for men, those with heavy drinking and alcohol abuse excluded), were collected for all patients. Data related to the diagnosis of AF including date of first diagnosis, history of stroke, and medications (anticoagulants, rate or rhythm control medications) were also recorded. Symptomatic severity of the patients was recorded according to the European Heart Rhythm Association score. Atrial fibrillation episodes that either lasted .7 days or required termination by cardioversion, either with drugs or by direct current cardioversion were defined as persistent; where AF episodes self-terminating within 7 days were defined as paroxysmal AF.1 The term ‘lone AF’ was used to describe AF patients who were under 60 years and had no history of cardiac disease or any risk factors for thromboembolism.1 All patients underwent transthoracic echocardiogram (TTE) and transoesophageal echocardiography to exclude left ventricular systolic dysfunction, valvular disease, and left atrial thrombus. Informed consent was taken from each patient before enrolment. The study was in compliance with the principles outlined in the Declaration of Helsinki and approved by the Institutional Ethics Committee.
Evaluation of left atrial dimension Each subject underwent a transthoracic two-dimensional (2D) guided M-mode echocardiogram using commercially available equipment (Vivid S6; GE Healthcare, Horten, Norway). All echocardiographic parameters were measured according to the recommendations of the American Society of Echocardiography5 by a single cardiologist blinded to the patient characteristics. Left atrial diameter was obtained in the parasternal long axis view. Left atrial area (LAA) and LA length were measured in the apical four-chamber and apical two-chamber views, respectively. Left atrial volume was derived using the biplane area– length method. Both LAA and LAV were measured at LV end-systole. Left atrial volume index was calculated based on the patient’s body surface area.5 Intra-observer variability testing for repeated LAV measurements from 25 subjects revealed an intra-class correlation coefficient of 0.943 (P , 0.001). Owing to this variability, LAVIR was defined as ≥5% reduction in LAVI following PVI.
M.U. Yalcin et al.
femoral vein and left femoral vein and artery punctures were performed with Seldinger technique. A 6 Fr steerable decapolar catheter (Dynamic DecaTM , Bard Electrophysiology) was placed in the coronary sinus. Single transseptal puncture by modified Brockenbrough technique (BRK-1TM , St Jude Medical) was performed under fluoroscopy and 8 Fr transseptal sheath (Biosense Webster) was placed into the LA. Once LA access was obtained, heparin boluses were repeatedly administered to maintain the activated clotting time between 300 and 350 s. The sheath was then exchanged for a 12 Fr steerable transseptal sheath (FlexCathTM , Medtronic CryoCath) over a guidewire (0.032 in., 180 cm Super StiffTM , St Jude Medical). During PVI with Arctic FrontTM (Medtronic CryoCath LP) (Arc-CB), baseline electrical potentials of all pulmonary veins (PVs) were recorded with a Lasso catheterTM (Biosense Webster, Inc.). On the other hand, in patients undergoing PVI with Arctic Front AdvanceTM (Medtronic Cryocath LP) (Arc-Adv-CB), the Achieve mapping catheterTM (Medtronic, Minneapolis, MN, USA) was used to document baseline PV potentials (PVPs). A 28-mm first generation CB catheter (Arc-CB) was used in 121 patients who underwent PVI between September 2011 and December 2012. A 28-mm second generation CB catheter (Arc-Adv-CB) was used in 39 patients who underwent PVI between December 2012 and July 2013. The cryoballoon was manoeuvred to all PV ostia by means of the steerable 12 Fr sheath and a guidewire inserted through the lumen of the balloon catheter. The balloon was inflated in the LA and then directed towards the PV ostia. Assessment of balloon occlusion was performed by injecting 50% diluted contrast through the cryoballoon catheter’s central lumen. Optimal vessel occlusion was considered to have been achieved when selective contrast injection showed total contrast retention with no flow back to the LA. Once occlusion was documented, cryothermal energy was started. A minimum of two consecutive freezing cycles were performed. The duration of each freezing cycle was 240 or 300 s. The procedure systematically began with the left superior PV, followed by the left inferior, right superior, and right inferior PVs. During ablation, if PVPs were visible during energy delivery, time to isolation was recorded when PVPs completely disappeared or were dissociated from LA activity. Acute procedural success was defined as elimination (or dissociation) of all PVPs.
Follow-up Following discharge from hospital, enrolled patients were scheduled for visits in the outpatient clinics at 1, 3, 6, and 12 months after ablation or earlier, if symptoms developed. At each visit, patients were evaluated for the recurrence of arrhythmias by means of physical examination, questioning for arrhythmia-related symptoms (palpitations, chest discomfort, fatigue, and dizziness), and a 12-lead ECG. A 24-h ambulatory Holter monitorization was conducted at 3, 6, and 12 months for all patients. Transthoracic echocardiogram, including LAV measurement and LAVI calculation, was performed at 12 months. The need for further oral anticoagulation was evaluated in the third month based on the CHA2DS2-VASc score. The outcome was assessed per the guidelines in the recent consensus document.4 A blanking period of 3 months was considered for the study. Any episode of AF, atrial flutter, or atrial tachycardia lasting at least 30 s and occurring in the blanking period was classified as an early recurrence. The same arrhythmias occurring after the blanking period were considered as late recurrences.
Statistical analysis Ablation procedure Ablation was performed under conscious sedation using boluses of midazolam. Invasive arterial blood pressure, oxygen saturation, and electrocardiogram (ECG) were monitored throughout the procedure. Right
Statistical analyses were performed using SPSS statistical software (version 21.0; SPSS Inc., Chicago, IL, USA). Normally distributed continuous parameters were presented as mean + standard deviation, where skewed continuous parameters were expressed as median (interquartile
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Predictors of left atrial volume index reduction
range, which was defined as minimum – maximum). Comparisons between baseline characteristics were performed by independent Student’s t, Mann– Whitney rank-sum, Fisher exact, or x 2 tests where appropriate. Cox proportional hazards regression for survival from AF recurrence was performed to identify predictors of recurrence; whereas univariate and multivariate linear regression analyses were performed to identify predictors of change in LAV following PVI. A twotailed P , 0.05 was considered statistically significant.
Table 1 The baseline demographic, clinical and echocardiographic parameters of the study population (n 5 160) Demographic parameters Gender: female (%) Age (years)
71 (44.40) 54.25 + 7.66
Clinical parameters
Results
BMI (kg/m2) Hypertension, n (%)
24.98 + 2.91 64 (40.00)
Patient characteristics and ablation procedure
Diabetes mellitus, n (%)
24 (15.00)
Coronary artery disease, n (%) Hyperlipidaemia, n (%)
20 (12.50) 40 (25.00)
A total of 160 patients (54.25 + 7.66 years, 44.40% female) were involved in the study. One hundred and eighteen patients (73.80%) had paroxysmal AF, whereas 42 patients (26.30%) had persistent AF (Table 1). Baseline characteristics of the study population are shown in Table 1. A total of 657 PVs were attempted for PVI. No patient was excluded due to anatomical reasons based on the computed tomography (CT) scan. Pulmonary vein isolation was performed by using either Arc-CB (n ¼ 121) or Arc-Adv-CB (n ¼ 39). Acute procedural success rate was 652/657 (99.23%). The five intact PVs were the right inferior PVs in patients who developed phrenic nerve palsy during isolation of right superior PVs.
Follow-up Patients were followed-up for 12 months. During the follow-up period, 124 of 160 patients (77.50%) were free of AF recurrence based on the aforementioned follow-up evaluation criteria. Cox proportional hazards regression analysis for survival from AF recurrence following ablation has revealed that LAVI was the only independent predictor (Table 2).
Predictors for reduction in left atrial volume index Baseline and follow-up characteristics of patients regarding the presence of LAVIR are shown in Table 3. Reduction in LAVI occurred in 120 patients. Left atrial volume index was significantly higher in patients without LAVI reduction when compared to those with LAVI reduction (34.00 + 4.00 vs. 30.15 + 2.40 mL/m2, P , 0.001). Patients without LAVIR were significantly older (56.93 + 5.24 vs. 53.36 + 8.14 years, P ¼ 0.002), had higher prevalence of hypertension (72.50 vs. 29.17%, P , 0.001), moderate mitral regurgitation (MR) (35.00 vs. 18.33%, P ¼ 0.049), and longer duration of AF [36 (18–100) vs. 36 (12–120) months, P ¼ 0.027]. Prevalence of persistent AF was higher (47.50 vs. 19.17%, P ¼ 0.001), whereas lone AF prevalence was lower (12.50 vs. 30.00%, P ¼ 0.047) in these patients. In addition, the rate of recurrence at 12 months was higher in patients without LAVIR (67.50 vs. 7.50%, P , 0.001) (Table 3). Linear regression analyses were performed to identify parameters independently associated with LAVIR following cryoballoon-based PVI for AF. Multivariate linear regression analysis is shown in Table 4. Age [hazard ratio (HR): 0.901, 95% confidence interval (CI): 0.828 –0.981, P ¼ 0.017], hypertension (HR: 0.151, 95% CI: 0.048–0.471, P ¼ 0.001), mild MR (HR: 5.327, 95% CI: 1.489 – 19.058, P ¼ 0.010), and AF recurrence (HR: 0.017, 95% CI: 0.005 –
Smoking, n (%)
53 (33.10)
Alcohol consumption, n (%) Duration of AF (months)
11 (6.90) 36 (12–120)
Type of AF, n (%) Paroxysmal AF Persistent AF
118 (73.80) 42 (26.30)
Lone AF
41 (25.60)
EHRA score (1– 4) 1
3 (2–4) 0
2
80 (50.00)
3 4
70 (43.80) 10 (6.30)
Number of antiarrhythmic drugs per patient (n) 1 2
70 (43.80) 76 (47.50)
3
14 (8.80)
ACEi/ARB use, n (%) Statin use, n (%)
58 (36.25) 32 (20.00)
Echocardiographic parameters LAD (mm) LAVI (mL/m2)
37.76 + 3.36 31.06 + 3.27
LV end-diastolic diameter (mm)
47.41 + 3.47
LV end-systolic diameter (mm) LV ejection fraction (%)
31.00 + 2.92 64.00 + 3.00
Mitral regurgitation Mild, n (%) Moderate, n (%)
124 (77.50) 36 (22.50)
Severe, n (%)
0
ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; AF, atrial fibrillation; BMI, body mass index; EHRA, European Heart Rhythm Association; LAD, left atrial diameter; LAVI, left atrium volume index; LV, left ventricular.
0.065, P , 0.001) were found to be independently associated with LAVIR (Table 4).
Discussion Up to now, there is paucity of data evaluating predictors of LAVIR following cryoballoon-based AF ablation. In this study, we have demonstrated that age, hypertension, severity of pre-procedural MR, and post-procedural AF recurrence are independent predictors of
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M.U. Yalcin et al.
Table 2 Cox regression analysis for identifying independent predictors of atrial fibrillation recurrence following ablation Variables
Univariate Cox regression analysis
Multivariate Cox regression analysis
HR (95% CI)
HR (95% CI)
................................................... P-Value
................................................... P-Value
............................................................................................................................................................................... Age (years)
1.030 (0.985–1.077)
0.197
1.007 (0.963–1.053)
0.765
Gender: male (%)
0.806 (0.421–1.543)
0.516
–
–
BMI (kg/m2) Hypertension (%)
1.052 (0.960–1.152) 1.152 (0.617–2.150)
0.275 0.657
– –
– –
Diabetes mellitus (%)
1.207 (0.533–2.733)
0.652
–
–
Coronary artery disease (%)
0.945 (0.395–2.263)
0.899
–
–
Smoking (%) Alcohol consumption (%)
1.173 (0.623–2.210) 0.957 (0.294–3.114)
0.621 0.942
– –
– –
Type of AF: persistent (%)
1.589 (0.842–2.994)
0.153
1.044 (0.495–2.204)
0.909
Duration of AF (months) LVEDD (mm)
1.001 (0.990–1.012) 1.104 (0.997–1.222)
0.818 0.058
– 1.058 (0.964–1.161)
– 0.237
LVEF (%)
0.976 (0.890–1.070)
0.601
LAVI (mL/m2) Mitral regurgitation: moderate (%)
1.337 (1.243–1.439) 1.272 (0.621–2.604)
,0.001* 0.510
– 1.345 (1.246–1.451) –
– ,0.001* –
AF, atrial fibrillation; BMI, body mass index; CI, confidence interval; HR, hazard ratio; LAVI, left atrial volume index; LVEDD, left ventricular end-diastolic diameter; LVEF, left ventricular ejection fraction. *P , 0.05.
Table 3 Baseline and follow-up characteristics of the study population regarding the presence of LAVIR Variables
LAVIR
............................................................ 1 (n 5 120)
P-Value
– (n 5 40)
............................................................................................................................................................................... Demographic parameters Gender: female (%) Age (years) Clinical parameters
54 (45.00)
17 (42.50)
0.927
53.36 + 8.14
56.93 + 5.24
0.002*
BMI (kg/m2)
24.84 + 2.97
25.40 + 2.72
Hypertension, n (%) Diabetes mellitus, n (%)
35 (29.17) 15 (12.50)
29 (72.50) 9 (22.50)
,0.001* 0.201
Hyperlipidaemia, n (%)
28 (23.33)
12 (30.00)
0.527
Coronary artery disease, n (%) Smoking, n (%)
13 (10.83) 39 (32.50)
7 (17.50) 14 (35.00)
0.408 0.923
0.297
Alcohol consumption, n (%)
8 (6.67)
3 (7.50)
0.960
Duration of AF (months) Type of AF: persistent, n (%)
36 (12–120) 23 (19.17)
36 (18– 100) 19 (47.50)
0.027* 0.001*
Lone AF, n (%)
36 (30.00)
5 (12.50)
0.047*
ACEi/ARB use, n (%) Statin use, n (%)
44 (36.67) 25 (20.83)
14 (35.00) 7 (17,50)
0.934 0.714
LAVI (mL/m2) LV end-diastolic diameter (mm)
30.15 + 2.40 47.24 + 3.51
34.00 + 4.00 48.00 + 3.32
LV end-systolic diameter (mm)
30.52 + 2.85
31.45 + 3.07
0.107
LV ejection fraction (%) Mitral regurgitation: moderate, n (%)
65.39 + 3.14 22 (18.33)
64.48 + 3.36 14 (35.00)
0.059 0.049*
9 (7.50)
27 (67.50)
Echocardiographic parameters ,0.001* 0.214
Follow-up parameters Recurrence, n (%)
,0.001*
ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; AF, atrial fibrillation; BMI, body mass index; LAVI, left atrial volume index; LAVIR, reduction in LAVI; LV, left ventricular. *P , 0.05.
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Predictors of left atrial volume index reduction
Table 4 Multivariate linear regression analysis for identifying independent predictors of LAVIR Variables
Multivariate linear regression analysis
.........................................
HR (95% CI)
P-Value
................................................................................ Age (years) Hypertension (%)
0.901 (0.828– 0.981) 0.151 (0.048– 0.471)
0.017* 0.001*
Paroxysmal AF (%)
2.838 (0.818– 9.847)
0.100
Lone AF (%) Duration of AF (months)
1.802 (0.317– 10.241) 1.019 (0.991– 1.048)
0.506 0.177
LAVI (mL/m )
0.925 (0.714– 1.198)
0.552
Mild mitral regurgitation (%) Recurrence (%)
5.327 (1.489– 19.058) 0.017 (0.005– 0.065)
0.010* ,0.001*
2
AF, atrial fibrillation; CI, confidence interval; LAVI, left atrial volume index; LAVIR, reduction in LAVI. *P , 0.05.
LAVIR following cryoballoon-based PVI for AF. To the best of our knowledge, this is the largest study in the literature investigating the predictors of LAVIR following AF ablation. In a previous study, LA diameter has been reported to be one of the parameters that has a predictive role in AF ablation outcomes.6 Successful catheter ablation has been shown to result in reverse LA remodelling.7,8 On the other hand, a meta-analysis has demonstrated that LAVI may show an increase in patients developing AF recurrence.3 The single study in the literature that is focused on predictors of LAVIR has reported that lone AF, hypertension, and ablation success are independent predictors for LAVIR.9 An increase in interstitial atrial fibrosis, which contributes to abnormal LA compliance, is known to occur as a part of the normal aging process.10 A reverse correlation between age and LA reverse remodelling has been reported in the previous study.11 Since irreversible changes, including extent of fibrosis and hypertrophy, increase with age, LA elasticity is reduced and LA remodelling is less probable even if volume overload is released by several interventions. In our study, age significantly reduced the possibility of LAVIR (HR: 0.901, P ¼ 0.017) following cryoballoon-based PVI compatible with the previous findings. In a previous study, LA diastolic stiffness was shown to be regulated by BMI, systolic blood pressure (SBP), and LV systolic function in patients with normal-sized LA; and by age, LAVI, and LV diastolic and systolic function in patients with enlarged LA.12 This finding is remarkable for showing that high SBP may have an adverse impact on LA structural remodelling even when dilatation has not occurred. Activated renin–angiotensin system and secondary elevation in afterload may have an influence on the atrial remodelling process in arterial hypertension.13 Our study has also shown that hypertension significantly reduced the possibility of LAVIR (HR: 0.151, P ¼ 0.001) following cryoballoon-based PVI. Volume overload in chronic severe MR has been demonstrated to cause LA remodelling. This has been suggested to be related with cellular hypertrophy and interstitial fibrosis that occur in the LA to compensate volume overload in order to prevent pulmonary
congestion.14,15 In several studies, LA reverse remodelling has been reported following mitral valve surgery or percutaneous valve intervention.16 Greater reverse remodelling has been observed with a greater degree of MR reduction.17 We did not include patients with severe MR in our study. Therefore, multivariate linear regression analysis was performed by comparing moderate with mild MR. Patients with mild MR had higher possibility of LAVIR when compared with those with moderate MR (HR: 5.327, P ¼ 0.010) in our study in accordance with the previous studies’ findings.
Study limitations We used 2D TTE to measure LAV, although performing measurements with magnetic resonance imaging or multislice CT could have been more accurate.
Conclusion Our study has shown that age, hypertension, and severity of MR are independent predictors of LAVIR following cryoballoon-based PVI. In addition, successful AF ablation was independently associated with LAVIR. Clinical implications of these findings need to be evaluated further in larger study populations. Conflict of interest: none declared.
References 1. Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation— developed with the special contribution of the European Heart Rhythm Association. Europace 2012;14:1385 –413. 2. Jayam VK, Dong J, Vasamreddy CR, Lickfett L, Kato R, Dickfeld T et al. Atrial volume reduction following catheter ablation of atrial fibrillation and relation to reduction in pulmonary vein size: an evaluation using magnetic resonance angiography. J Interv Card Electrophysiol 2005;13:107 –14. 3. Jeevanantham V, Ntim W, Navaneethan SD, Shah S, Johnson AC, Hall B et al. Meta-analysis of the effect of radiofrequency catheter ablation on left atrial size, volumes and function in patients with atrial fibrillation. Am J Cardiol 2010;105: 1317 –26. 4. Calkins H, Kuck KH, Cappato R, Brugada J, Camm AJ, Chen SA et al. 2012 HRS/ EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design. Europace 2012;14:528 – 606. 5. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440 –63. 6. Abecasis J, Dourado R, Ferreira A, Saraiva C, Cavaco D, Santos KR et al. Left atrial volume calculated by multi-detector computed tomography may predict successful pulmonary vein isolation in catheter ablation of atrial fibrillation. Europace 2009;11:1289–94. 7. Reant P, Lafitte S, Jais P, Serri K, Weerasooriya R, Hocini M et al. Reverse remodeling of the left cardiac chambers after catheter ablation after 1 year in a series of patients with isolated atrial fibrillation. Circulation 2005;112:2896 –903. 8. Hof IE, Vonken EJ, Velthuis BK, Wittkampf FH, van der Heijden JF, Neven KG et al. Impact of pulmonary vein antrum isolation on left atrial size and function in patients with atrial fibrillation. J Interv Card Electrophysiol 2014;39:201–9. 9. Fredersdorf S, Ucer E, Jungbauer C, Dornia C, Eglmeier J, Eissnert C et al. Lone atrial fibrillation as a positive predictor of left atrial volume reduction following ablation of atrial fibrillation. Europace 2014;16:26 –32. 10. Hayashi H, Wang C, Miyauchi Y, Omichi C, Pak HN, Zhou S et al. Aging-related increase to inducible atrial fibrillation in the rat model. J Cardiovasc Electrophysiol 2002;13:801 –8.
Page 6 of 6 11. Hyllen S, Nozohoor S, Meurling C, Wierup P, Sjogren J. Determinants of left atrial reverse remodeling after valve surgery for degenerative mitral regurgitation. J Heart Valve Dis 2013;22:2– 10. 12. Miyoshi H, Oishi Y, Mizuguchi Y, Iuchi A, Nagase N, Ara N et al. Association of left atrial reservoir function with left atrial structural remodeling related to left ventricular dysfunction in asymptomatic patients with hypertension: evaluation by two-dimensional speckle-tracking echocardiography. Clin Exp Hypertens 2015;37:155–65. 13. Kim SJ, Choisy SC, Barman P, Zhang H, Hancox JC, Jones SA et al. Atrial remodeling and the substrate for atrial fibrillation in rat hearts with elevated afterload. Circ Arrhythm Electrophysiol 2011;4:761–9. 14. Braunwald E, Awe WC. The syndrome of severe mitral regurgitation with normal left atrial pressure. Circulation 1963;27:29 –35.
M.U. Yalcin et al.
15. Anne W, Willems R, Roskams T, Sergeant P, Herijgers P, Holemans P et al. Matrix metalloproteinases and atrial remodeling in patients with mitral valve disease and atrial fibrillation. Cardiovasc Res 2005;67:655 –66. 16. Le Bihan DC, Della Togna DJ, Barretto RB, Assef JE, Machado LR, Ramos AI et al. Early improvement in left atrial remodeling and function after mitral valve repair or replacement in organic symptomatic mitral regurgitation assessed by threedimensional echocardiography. Echocardiography 2014. [Epub ahead of print: doi: 10.1111/echo.12817]. 17. Grayburn PA, Foster E, Sangli C, Weissman NJ, Massaro J, Glower DG et al. Relationship between the magnitude of reduction in mitral regurgitation severity and left ventricular and left atrial reverse remodeling after MitraClip therapy. Circulation 2013; 128:1667 –74.
