1 The Key Labo rato ry of Cardiovascular Remodeling a n d Function Research, Chinese Ministry of Education, Chinese National Health Commission a n d Chinese Academy of Medical Sciences, The State a n d Sha n dong Province Joint Key Labo rato ry of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital of Sha n dong University, Jinan, China
Jingquan Zhong, Department of Cardiology, Qilu Hospital of Sha n dong University, No. 44 Wenhua Xi Road, Jinan 250012, Sha n dong Province, China. Phone: +86－531－82169335
Background：Catheter ablation is an approved therapy fo r symptomatic drug refracto ry atrial fibrillation (AF). The current guideline determines thatage as a sole facto r shouldnot be an excluding criteria fo r catheter ablation; however, the guideline does not provide specific data to elderly group. The aim of this single center retrospective study is to evaluate the safety a n d efficacy of cryoballoon (CRYO) as well as redio－frequency (RF) ablation in patients ≥75 years.
Methods a n d results: Sixty－five consecutive patients received pulmonary vein isolation (PVI) using the second－generation CRYO, the mean age was 79.5±4.2 years; Seventy－three consecutive patients received PVI using RF ablation, the mean age was 78.5±3.2 years. During 13.8±6.4 monthsof follow－up, single procedure success rates fo r the CRYO a n d RF group were 72.3％ a n d 75.3％, respectively (p=0.685). No severe complications such as cardiac perfo ration, atrio－esophageal fistula occurred in the CRYO group, transient phrenic nerve palsy only occurred in the CRYO group (1 vs 0, p=0.287). Other complications such as local puncture site hematoma did not differ between the two groups.
Conclusions：Our data strengthened the value of CRYO ablation in elderly AF patients fo r its easy feasibility a n d safety, with similar success rates when compared with RF ablation.
Conclusions：cryoballon; radio－frequency; elderly group
Atrial fibrillation is the most prevalent arrhythmia seen in clinical practice reaching a prevalence of 8％ in those aged older than 80 years(1), it is associated with decreased quality of life a n d increased mo rbidity, resulting in increased hospitalization rates,especially in elderly population(2). As the prevalence of atrial fibrillation increases dramatically with advancing age, the necessity of treating elderly patients with AF is noticeably growing.
Catheter ablation (CA) is one of the most impo rtant managementstrategies to reduce AF burden a n d AF－associated complications(3). However, in elderly patients CA is often challenged due to long procedure duration, peri－procedure complications a n d post－ablation recurrence(4, 5). CRYO technology has been developed aiming at facilitation of the ablation procedure(6). Recent trials have verified this technology was non－inferio r to the point by point ablation using radio frequency with respect to success a n d complication rates(7), but data of the safety a n d efficacy of CRYO ablation in the elderly population has not been well documented.
In this study, we aimed to assess the safety a n d efficacy of AF ablation using the second－generation CRYO as compared with conventional irrigated RF ablation in patients ≥ 75 years.
Between Jan 2015 a n d July 2017, patients ≥ 75 years with indication fo r AF ablation were enrolled in this single center retrospective study. Patients with left atrial (LA) thrombus, uncontrolled thyroid dysfunction, known bleeding diathesis o r intoleranceof o ral anticoagulation, severe valvular disease, respirato ry insufficiency, previous catheter ablation o r surgery were excluded.Info rmed consent was taken from each patient befo re theprocedure. The study protocol was approved by the institutional review board of Qilu hospital.
Continuous variables were described as mean ± sta n dard deviation a n d catego rical variables were expressed as percentages. Continuous variables were compared using the Student t test, a n d catego rical data were compared using Chi－square analysis. Statistical analyses were perfo rmed using SPSS statistical software (version 22.0; SPSS Inc., Chicago, IL, USA). A two－tailed p<0.05 was considered statistically significant.
1. Baseline characteristics
A total of 138 patients (sixty－five patients of CRYO group a n d seventy－three patients of RF group) with paroxysmal AF were included. Baseline characteristics of the study population were summarized in Table 1. The mean age was 79.5±4.2 years in the CRYO group a n d 78.5±3.2 in the RF group (p=0.115). Mo re male patients were enrolled in the RF group. The duration of AF a n d anti－arrhythmic drugs intervention befo re ablation were similar between groups. Patients in the CRYO group had lower BMI, LA diameter, CHA2DS2VASc Sco re a n d HASBLED sco re, while had mo re dyslipidemia prio r to ablation. Other cardiovascular risk facto rs such as hypertension, sleep apnoea did not differ between the two groups.
AF, atrial fibrillation;BMI, body mass index; LA, left atrium
Values are expressed as mean±SD o r as n (％).
2. Procedural characteristics
All procedures were perfo rmed under conscioussedation a n d analgesia. The procedural duration was significantly sho rter in the CRYO group (132.6±35.2vs. 159.2±49.2, p<0.001), but the fluo roscopy time was significantly longer in the CRYO group (23.5±15.2 vs. 15.3±8.7, p<0.001). PV abno rmality was observed in fifteen patients of the CRYO group a n d nineteen patients of the RF group (23.0％ vs. 26.0％, p=0.688). The rates of acute success in isolating PV did not differ between the CRYO a n d the RF group. It was noticed the CRYO procedure required mo re contrast medium (Iopromide, 48.3±13.1 vs. 26.9±5.2, p<0.001). After procedure, fifty－five patients of the CRYO group demonstrated sinus rhythm (84.6％ vs. 97.2％ in the RF group, p=0.008), so electrical cardioversion was perfo rmed mo re after the freeze cycle a n d PVI was re－confirmed in sinus rhythm.
Values are expressed as mean±SD o r as n (％).
Overall, during 13.8±6.4 months of follow－up, single procedure success rates were 72.3％ in the CRYO group a n d 75.3％ in the RF group (p=0.685). During intrahospital stay, thirteen patients of the CRYO group had onset of AF (20.0％ vs. 12.3％ in the RF group, p=0.219), that was reverted to sinus rhythm by intravenousanti－arrhythmic drugs. Early recurrence of atrial tachyarrhythmia (ATA) within the first 3 months (blanking period) was similar between two groups (49.2％ in the CRYO group vs. 38.3％ in the RF group, p=0.198). AAD was prescribed to all patients after index procedure.Continuedmedication with Classes I o r III AADs after 3 months was comparable between groups (23.0％ of the CRYO group vs. 15.0％ of the RF group, p=0.229). All patients who underwent redo ablation fo r recurrent ATA were treated with RF ablation, among which, patients of the CRYO group have mo re typical atrial flutter recurrence (13.8％ vs. 4.1％, p=0.042), while patients of RF group have mo re left AT during the second procedure (17.8％ vs. 4.6％, p=0.015). During follow－up, the renal function was also continuous monito red by creatinine clearance rate, it showed no difference between the two groups (p=0.127).
Values are expressed as mean±SD o r as n (％).
4. Adverse events
The number of patients with peri－procedural complications were comparable in the CRYO a n d RF group (9.2％ vs. 15.0％, p=0.297). Details of complication rates a n d types were given in Table 4, Severe complications such as cardiac perfo ration occurred only in the RF group (1 vs 0, p=0.343), that was managed by pericardial puncture. There was one atrio－esophageal fistula case in the RF group (1 vs 0, p=0.343), the patients had to take surgical intervention a n d a patch closure of the left atrial fistula. Transient phrenic nerve palsy (PNP) occurred only in the CRYO group (1 vs 0, p=0.287). The PNP case resolved spontaneously during the follow－up. Six groin complications occurred in both groups, two in CRYO group a n d four in RF group (p=0.745), the groin complication prolonged hospital stay 2 days. No severe procedure－related deaths occurred in both groups.
Values are expressed as mean±SD o r as n (％).
Catheter ablation of AF in appropriately selectedindividuals is associated with significantly better AF－freesurvival than rhythm control with AADs with o r withoutcardioversion(8).However, studies of AF ablation have generallyincluded relatively young individuals a n d may notreflect the demographic characteristics of AF most commonlyencountered in clinical practice(9－11).Individuals aged 75 a n d older were excludedfrom all above trials, whereas AF is mo re commonly foundin elderly adults a n d is mo re resilient to catheter ablation. Therefo re this study aimed to evaluate the safety a n d efficacy of cryoballoon (CRYO) as well as radio－frequency (RF) ablation in patients ≥75 years.
The main findings of our study are as following：(1) Success rates of cryoballoon ablation was comparable with radiofrequency ablation; (2) Cryoballoon abaltion rarely had servere, fatal complications during the procedure; (3) Although cryoballoon procedure required mo re usage of contrast medium, influence of renal function can hardly be observed.
Procedural a n d clinical outcome
Even though point by point RF ablation is still the most commonly applied technique fo r PVI, thecryoballoon has rapidly evolved as a powerful one－shot tool(12). In our study, patients treated withthe second－generation cryoballoon had significantly sho rter procedural duration times than those treatedwith RF ablation,it was noticed that although procedure times of CRYO groupwas sho rter ascompared to RF－guided ablation, fluo roscopy times was longer a n d the radiation contrast mediawas significantly mo re when usingthe cryoballoon. Reactions to excessive contrast media do occur a n d can be life threatening, therefo re the decline in renal function were regularly monito redduring the follow－up(13). It was observed that the renal function monito red by creatinine clearance rate was barely affected by intravenous administration of iodinated contrast, a n d it showed no difference between the two groups. In our analysis, we observed that the sho rt－mid－term recurrence rates of PVI in patients using the cryoballon were slightly higher, the mechanism of AF in this setting may be different from that of the patient’s clinical arrhythmia a n d may resolve completely upon resolution of the inflammato ry process(14). We showed approximately similar acute success rates a n d comparable long－term arrhythmia－free survival rates inthe CRYO a n d RF group, 72.3％ a n d 75.3％, respectively,which is consistentwith recent studies comparing AF ablation energy sources(15). Patients with a regular atrial tachycardia of newonset may complain of wo rsening symptoms due to a fastermean ventricular rate than during their pre－ablation AF(16). In our analysis fo r the second procedure ablation, the atrial tachycardias after RF ablation usually o riginated in theLA, while patients of the CRYO group have mo re typical atrial flutter recurrence. The observationthat the lower duration of procedure, comparable long－term arrhythmia－free survival rates,has made potential implications fo r the CRYO choice of elderly patients AF in clinical practice.
Safety perfo rmance
Catheter ablation of AF is one of the most complex interventionalelectrophysiologic procedures. Particular attention is focused on the mostfrequently occurring complications a n d those likely to resultin prolonged hospitalization, long－term disability, o r death(17). Phrenic nerve injury is one of the most concerning complications of cryoballoon ablation,mo re frequently inthe right superio r PV(18). In our study, PNP occurred only in CRYO group, the case resolved spontaneously during follow－up. No severe complication such as procedure－related death, cardiac perfo ration, atrio－esophageal fistula occurred in the CRYO group. Consequently, elderly patients with good functional status should be carefully evaluateda n d considered to receive cryoballoon with a favo rablesuccess rates a n d rare servere complication rate.
1. Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation as an independent risk facto r fo r stroke: the Framingham Study. Stroke. 1991;22(8):983－8.
2. Go AS, Hylek EM, Phillips KA, Chang Y, Henault LE, Selby JV, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications fo r rhythm management a n d stroke prevention: the AnTicoagulation a n d Risk Facto rs in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285(18):2370－5.
3. Kosich F, Schumacher K, Potpara T, Lip GY, Hindricks G, Ko rnej J. Clinical sco res used fo r the prediction of negative events in patients undergoing catheter ablation fo r atrial fibrillation. Clin Cardiol. 2018.
4. Jilek C, Lewalter T. [Ablation fo r atrial fibrillation in the elderly]. Herzschrittmacherther Elektrophysiol. 2017;28(1):39－47.
5. Vlachos K, Efremidis M, Letsas KP, Bazoukis G, Martin R, Kalafateli M, et al. Low－voltage areas detected by high－density electroanatomical mapping predict recurrence after ablation fo r paroxysmal atrial fibrillation. J Cardiovasc Electrophysiol. 2017;28(12):1393－402.
6. Murray MI, Arnold A, Younis M, Varghese S, Zeiher AM. Cryoballoon versus radiofrequency ablation fo r paroxysmal atrial fibrillation: a meta－analysis of ra n domized controlled trials. Clin Res Cardiol. 2018;107(8):658－69.
7. Kuck KH, Brugada J, Furnkranz A, Metzner A, Ouyang F, Chun KR, et al. Cryoballoon o r Radiofrequency Ablation fo r Paroxysmal Atrial Fibrillation. N Engl J Med. 2016;374(23):2235－45.
8. Calkins H, Reynolds MR, Specto r P, Sondhi M, Xu Y, Martin A, et al. Treatment of atrial fibrillation with antiarrhythmic drugs o r radiofrequency ablation: two systematic literature reviews a n d meta－analyses. Circ Arrhythm Electrophysiol. 2009;2(4):349－61.
9. Packer DL, Kowal RC, Wheelan KR, Irwin JM, Champagne J, Guerra PG, et al. Cryoballoon ablation of pulmonary veins fo r paroxysmal atrial fibrillation: first results of the No rth American Arctic Front (STOP AF) pivotal trial. Journal of the American College of Cardiology. 2013;61(16):1713－23.
10. Mo rillo CA, Verma A, Connolly SJ, Kuck KH, Nair GM, Champagne J, et al. Radiofrequency ablation vs antiarrhythmic drugs as first－line treatment of paroxysmal atrial fibrillation (RAAFT－2): a ra n domized trial. JAMA. 2014;311(7):692－700.
11. Wilber DJ, Pappone C, Neuzil P, De Paola A, Marchlinski F, Natale A, et al. Comparison of antiarrhythmic drug therapy a n d radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a ra n domized controlled trial. JAMA. 2010;303(4):333－40.
12. Okumura Y, Watanabe I, Iso K, Takahashi K, Nagashima K, Sonoda K, et al. Mechanistic Insights Into Durable Pulmonary Vein Isolation Achieved by Second－Generation Cryoballoon Ablation. J Atr Fibrillation. 2017;9(6):1538.
13. Beckett KR, Mo riarity AK, Langer JM. Safe Use of Contrast Media: What the Radiologist Needs to Know. Radiographics. 2015;35(6):1738－50.
14. A n drade JG, Khairy P, Guerra PG, Deyell MW, Rivard L, Macle L, et al. Efficacy a n d safety of cryoballoon ablation fo r atrial fibrillation: a systematic review of published studies. Heart Rhythm. 2011;8(9):1444－51.
15. Mo rtsell D, Arbelo E, Dagres N, Brugada J, Laroche C, Trines SA, et al. Cryoballoon vs. radiofrequency ablation fo r atrial fibrillation: a study of outcome a n d safety based on the ESC－EHRA atrial fibrillation ablation long－term registry a n d the Swedish catheter ablation registry. Europace. 2018.
16. Ouyang F, Antz M, Ernst S, Hachiya H, Mavrakis H, Deger FT, et al. Recovered pulmonary vein conduction as a dominant facto r fo r recurrent atrial tachyarrhythmias after complete circular isolation of the pulmonary veins: lessons from double Lasso technique. Circulation. 2005;111(2):127－35.
17. Cappato R, Calkins H, Chen SA, Davies W, Iesaka Y, Kalman J, et al. Updated wo rldwide survey on the methods, efficacy, a n d safety of catheter ablation fo r human atrial fibrillation. Circ Arrhythm Electrophysiol. 2010;3(1):32－8.
18. Wei HQ, Guo XG, Zhou GB, Sun Q, Yang JD, Xie HY, et al. Procedural findings a n d clinical outcome of second－generation cryoballoon ablation in patients with variant pulmonary vein anatomy. J Cardiovasc Electrophysiol. 2019;30(1):32－8.