Indian experience with cryoablation for paroxysmal and persistent atrial fibrillation

Abstract

Background

While the safety and efficacy of cryoablation procedures have been well-established in Western populations, data regarding these outcomes in the subcontinent remain limited.

Methods

This retrospective observational study included patients with paroxysmal atrial fibrillation (PAF) or persistent atrial fibrillation (PsAF) treated with cryoballoon catheter ablation according to standard clinical practice. The primary efficacy endpoints (mean follow-up of 15.3 months) were freedom from AF/atrial flutter (AFL)/atrial tachycardia (AT) lasting ≥30 s. The primary safety endpoint was the occurrence of serious procedure-related adverse events within 30 days of the procedure.

Results

The study population included 66 consecutive patients with recurrent symptomatic atrial fibrillation despite medications and underwent the cryoablation procedure for rhythm control. The cohort had a mean age of 55 ± 14 years, was 77 % male, had a CHA2DS2-VASc score of 1.63 ± 1.53, and had been diagnosed with AF for a mean of 2.93 ± 3.25 years before cryoablation. Patients with PAF comprised 75.8 % of the total cohort. The PsAF subgroup had a significantly larger mean left atrial (LA) diameter (42 mm vs. 36 mm; p < 0.01), lower LVEF (57 % vs 63 %; p = 0.016), fewer presyncope episodes (6 % vs. 30 %; p = 0.048), and higher amiodarone use within last one year (69 % vs. 22 %; p < 0.01). Two serious procedure-related events (3.03 %) occurred (phrenic nerve injury), both of which resolved within 3 months’ follow-up. Freedom from recurrence of atrial arrhythmia at 12 months was 71 % (95 % CI 55–81 %), with a significant difference between PAF 84 % (95 % CI 68–92 %) and PsAF 34 % (95 % CI 10–60 %) groups. Presence of atrial arrhythmia at the beginning of the study (87 % vs 51 %) and failure to terminate it after completion of ablative procedure, requiring electrical cardioversion, impose a higher risk (83 % vs 28 %) of recurrence. No difference was found between the PVI and PVI + groups.

Conclusions

Cryoballoon ablation demonstrated efficiency, safety, and effectiveness in treating patients with paroxysmal and persistent AF. 12-month atrial arrhythmia-free survival rates were significantly higher in patients with PAF compared to those with PsAF. Pre-procedural atrial arrhythmias and post-procedural atrial arrhythmias requiring cardioversion are associated with a higher risk of recurrence. Major procedural adverse effects were comparable to those reported in global standards.

• •What is already known on this topic – Safety and efficacy of cryoablation procedures have been well-established in Western populations.
• •What this study adds – To document the safety and efficacy profile of cryoablation in Indian subcontinent, alongside insights into both short-term and intermediate-term outcomes
• •How this study might affect research, practice or policy – May facilitate widespread application of this procedure within the subcontinent's population

1. Introduction

AF is the most common sustained arrhythmia encountered in clinical practice. AF is associated with an increased risk of stroke and heart failure, leading to reduced overall survival [1]. The EAST-AFNET 4 trial showed that early rhythm control significantly reduced the composite primary outcome of cardiovascular death, stroke, and hospitalisation for worsening heart failure and acute coronary syndrome by 21 % but increased serious adverse events related to AAD therapy [2]. In contrast, The EARLY-AF trial sought to evaluate the role of initial cryoballoon ablation versus initial AAD therapy as the first treatment of AF in AAD-naïve patients [3]. This trial demonstrated that an initial cryoballoon ablation approach was superior to AADs for the outcomes of atrial tachyarrhythmia recurrence, arrhythmia burden and quality of life (QOL).

For the treatment of symptomatic paroxysmal atrial fibrillation (PAF), pulmonary vein electrical isolation by catheter ablation is considered a first-line therapy, with pulmonary vein isolation (PVI) serving as a fundamental and standard approach for both paroxysmal and persistent AF.

The introduction of cryoballoon ablation (CBA) for pulmonary vein (PV) isolation represented a technological advancement, enabling single energy applications to create encircling lesions at the PV antral level, contrasting with the point-by-point energy delivery characteristic of conventional RFCA. The FIRE AND ICE trial demonstrated the non-inferiority of the cryoballoon to irrigated-tip radiofrequency ablation (RFA) in terms of efficacy and safety, establishing CBA as one of the most widely adopted ablation technologies for AF treatment [4].

While the safety and efficacy of cryoablation procedures have been well-established in Western population, there is meagre data for the procedural outcomes from South Asia. This paucity of data has consequently restricted the widespread application of this procedure within the subcontinent. This study aims to address this knowledge gap by documenting the safety and efficacy profile of cryoablation in this region, alongside insights into both short-term and intermediate-term outcomes.

2. Materials and methods

This single-centre retrospective observational study investigated the outcomes following cryoablation for symptomatic AF at a tertiary referral centre in India, over 30 months.

• •Study population and data collection

The study population included 66 consecutive patients with recurrent symptomatic atrial fibrillation despite medications and underwent the cryoablation procedure from 2022 to 2024. All patients were on beta-blockers (metoprolol or bisoprolol preprocedurally). Clinical data was collected from patient records, including baseline demographics, medical history, AF characteristics, pre-procedural workup (echocardiography, chest X-ray, CT scan), procedural details (fluoroscopy time, energy delivered, complications), post-procedural outcomes (arrhythmia recurrence, medications, length of stay, 30-day adverse events), and follow-up assessments (at 1, 3, 6, and 12 months) to determine sustained freedom from AF (after 90-day blanking period) and long-term complications.

• •Ablation procedure:

The initial case was conducted with the guidance of a cryoablation expert. Subsequently, all procedures were performed independently by the same team, with the lead cardiac electrophysiologist possessing over 20 years of experience in pulmonary vein isolation by radiofrequency ablation. All patients underwent pulmonary vein isolation using a 28 mm cryoablation balloon (Medtronic, United States) according to the institute's prespecified clinical protocol. Preprocedural CT scans were performed in most patients to delineate the pulmonary vein anatomy. Patients who didn't have a recent CT scan underwent transoesophageal echocardiography one day prior to the procedure to exclude a left atrial clot. A transseptal puncture, optimally positioned low and anterior, was executed under fluoroscopic/intracardiac echocardiography (ICE) guidance as per standard protocol. After transseptal access, a FlexCath Advance™ (Medtronic, United States) sheath with 28 mm cryoballoon catheter was used for cryoablation. The Achieve™ mapping catheter was used for left atrial and PV potential mapping. Pulmonary vein (PV) angiography with 1–2 mL of contrast injection was performed to verify complete PV sealing by the balloon. The sealing was also confirmed with pressure wave forms from balloon tip as well as using ICE if available. Challenges in achieving complete pulmonary vein (PV) occlusion (sealing) were addressed through the implementation of both the Hockey stick and modified Hockey stick techniques. These strategies were primarily employed to assure the effective and complete isolation of the PVs, particularly the inferior pulmonary veins. Optimal isolation of the right superior pulmonary vein was ensured with the proximal seal technique. Left sided common pulmonary veins required segmental isolation. Oesophageal temperature and diaphragmatic movements were monitored during ablation. Freezing was stopped if oesophageal temperature fell below 27 °C. The phrenic nerve was stimulated with a quadripolar catheter positioned in the high SVC, and diaphragmatic movement was comprehensively monitored using palpation over the abdomen, a compound muscle action potential electrogram of the diaphragm, intermittent fluoroscopy, or a pulse Doppler waveform in intracardiac echocardiography. Pre- and post-procedure electroanatomic mapping was performed by merging the real-time geometry using 3D model segmentation by Ensite Verismo (Abbott, United States) in all cases to confirm pulmonary vein isolation (scar in all cases; non-conduction wherever feasible; representative image in Fig. 1). A hybrid approach was employed, wherein radiofrequency ablation of any inducible sustained atrial arrhythmias was performed following cryoablation. In all patients, the study commenced with the patient's presenting rhythm (either atrial arrhythmia or sinus rhythm) and concluded upon achieving a sinus rhythm, whether induced by ablation or achieved via electrical cardioversion. In patients with ongoing atrial fibrillation, cryoablation was completed and cardioverted/terminated during cryoapplication. Then, remapping was done in sinus rhythm to ensure isolation.

Fig. 1.

Pre- and Post-procedure electroanatomical mapping to confirm pulmonary vein isolation (representative image).

2.1. Follow up

All patients received flecainide or amiodarone and anticoagulation until first follow up as tolerated. Rhythm control drugs and anticoagulation were stopped according to CHA2DS2VASc score or maintained in minimal dose according to clinical symptoms. All patients were followed up at 1 month in a dedicated arrhythmia clinic and regular follow-up assessments (at 1, 3, 6, and 12 months) to determine sustained freedom from AF and long-term complications. AF recurrence was identified using office ECG at every visit or clinical symptom of recurrent palpitation. Those with palpitations underwent evaluation with a 24 h or 3-day Holter study to identify atrial fibrillation at clinicians discretion.

2.2. Statistical analysis

Categorical data are summarised as frequencies and percentages, and groups are compared using the Chi-square test/Fischer exact test. Descriptive data for continuous variables are presented as mean ± SD or median with range when appropriate. Analyses of continuous data are performed with the use of a Paired t-test for parametric distribution. A p-value of <0.05 will be considered statistically significant. The primary endpoint (freedom from AF episodes) is analysed using Kaplan-Meier curves and compared between groups using log-rank tests. Secondary outcomes are analysed with appropriate statistical methods depending on data distribution.

3. Results and analysis

• •Baseline characteristics

Sixty-six subjects were enrolled between April 2022 and October 2024, with a mean follow-up of 15.3 months (SD 8.8 months). Baseline clinical characteristics, procedural details, efficacy, safety, and short-term outcomes were analysed. Baseline patient characteristics are detailed in Table 1. The cohort had a mean age of 55 ± 14 years, was 77 % male, had a CHA2DS2VASc score of 1.63 ± 1.53, and had been diagnosed with AF for a mean of 2.93 ± 3.25 years prior to cryoablation. The prevalence of typical atrial flutter, atrial tachycardia, and tachy-brady syndrome was 12 %, 9 %, and 18 %, respectively. Beta-blockers (88 %) were the most commonly prescribed pre-procedural medication, followed by amiodarone (33 %) and flecainide (27 %). Structural heart disease was present in 26 % of patients, including 13 % with concentric left ventricular hypertrophy (LVH), 1.5 % with apical hypertrophic cardiomyopathy (HCM), and 4.5 % with mitral valve prolapse (Supplementary Table 1). Mean atrial diameter and left ventricular ejection fraction (LVEF) were 38 mm and 62 %, respectively. Patients with paroxysmal AF (PAF) comprised 75.8 % of the total cohort. The PsAF subgroup had a significantly larger mean left atrial (LA) diameter (42 mm vs. 36 mm; P < 0.01), lower LVEF (57 % vs. 63 %; P = 0.016), fewer presyncope episodes (6 % vs. 30 %; p = 0.048), and higher amiodarone use (69 % vs. 22 %; p < 0.01). Other baseline characteristics were similar between the subgroups. Prior ablation history has been depicted in Table 2.

Table 1.

Baseline patient characteristics.

Subject characteristics	Total cohort (N = 66)	Paroxysmal AF (N = 50)	Persistent AF (N = 16)	P‐value
Male sex (N [%])	50 (77.27)	38 (76.00)	13 (81.25)	0.476
Age in years (mean ± STD)	55.19 (13.79)	54.84 (13.62)	56.31 (14.71)	0.713
CHA2DS2‐VASc Score (mean ± SD)	1.63 (1.53)	1.56 (1.50)	1.87 (1.66)	0.479
Years diagnosed with AF (mean ± SD)	2.93 (3.25)	2.73 (2.83)	3.58 (4.36)	0.362
History of atrial flutter (N [%])	8 (12.12)	6 (12.00)	2 (12.50)	0.628
History of atrial tachycardia (N [%])	6 (9.09)	6 (12.00)	0 (0)	0.175
Tachy-brady syndrome (N [%])	12 (18.18)	12 (24.00)	0 (0)	0.093
Left atrial diameter in mm (mean ± SD)	37.83 (6.32)	36.42 (5.54)	42.25 (6.75)	0.0009
Left ventricular hypertrophy (N [%])	16 (24.24)	13 (26)	3 (18.75)	0.412
Structural heart disease (N [%])	17 (25.76)	14 (28)	3 (18.75)	0.351
Left ventricular ejection fraction in % (mean ± SD)	61.95 (8.9)	63.44 (6.65)	57.31 (3.31)	0.016
Hypertension (N [%])	29 (43.94)	9 (56.25)	20 (40.00)	0.254
Diabetes (N [%])	19 (28.79)	7 (43.75)	12 (24.00)	0.129
Dyslipidaemia (N [%])	13 (19.70)	11 (22.00)	2 (12.50)	0.332
Hypothyroidism (N [%])	12 (18.18)	8 (16.00)	4 (25.00)	0.319
Coronary artery disease (N [%])	8 (12.12)	7 (14.00)	1 (6.25)	0.372
Sleep apnoea (N [%])	15 (22.73)	10 (20)	5 (31.25)	0.350
Palpitations (N [%])	66 (100)	50 (100)	16 (100)	NA
Presyncope (N [%])	16 (24.24)	15 (30.00)	1 (6.25)	0.048
Prior medications (N [%])
Amiodarone	22 (33.33)	11 (22.00)	11 (68.75)	0.001
Beta blockers	58 (87.88)	46 (92.00)	12 (75.00)	0.090
Flecainide	18 (27.27)	15 (30.00)	3 (18.75)	0.296
Cardiac CT (N [%])	64 (96.97)	50 (100)	14 (87.5)	0.056
LA volume (mean ± STD)	97.64 (31.49)	92.27 (24.82)	116.07 (44.21)	0.011
No. of Pulmonary veins
5	12 (18.18)	11 (22.00)	1 (6.25)	0.188
Additional pulmonary veins	12 (18.88)	11 (22.00)	1 (6.25)	0.188
LMPV	1 (1.52)	1 (2.00)	0 (0.00)	0.572
RMPV	11 (16.67)	10 (20.00)	1 (6.25)	0.572
Common pulmonary veins	16 (24.24)	11 (22.00)	5 (31.25)	0.355
LCV	14 (21.21)	9 (18.00)	5 (31.25)	0.579
RCV	2 (3.03)	2 (4.00)	0 (0.00)	0.579

Table 2.

Prior ablation history in the study cohort (N = 66).

Prior ablation	NO [Total 6]
Cavotricuspid Isthmus	1
Cavotricuspid isthmus and Left WACA	1
Pulmonary vein isolation – RFA	1
Left atrial flutter	1
Atrioventricular nodal reentrant tachycardia	1
Right ventricular outflow tract ventricular tachycardia	1

Preprocedural cardiac computed tomography (CT) was performed in 97 % of the cohort, excluding two patients (Table 1). In one patient, a history of kidney transplantation contraindicated contrast CT. In the other, significant diabetic nephropathy precluded CT. CT imaging revealed a mean left atrial (LA) volume of 97 mL (SD 32 mL), with significantly greater LA dilation in the persistent AF (PsAF) group compared to the paroxysmal AF (PAF) group (116 mL vs. 92 mL, p = 0.011). The majority of the cohort (82 %) had four pulmonary veins, while 18 % had five. The additional pulmonary veins were left middle (1.5 %) and right middle (16.7 %) pulmonary veins. Common pulmonary veins were observed in 24 % of the cohort, with left-sided common veins being the most prevalent.

• •Procedure characteristics

Procedural data are detailed in Table 3. Intracardiac echocardiography (ICE) was used in 26 % of the cohort. The mean left atrial (LA) dwell time was 61 ± 19 min, and the average fluoroscopy time was 40 ± 17 min. All targeted pulmonary veins (PVs) were acutely isolated during the index procedure. However, documentation of PV potential disappearance in all the pulmonary veins during cryoapplication was observed in only 36 % of patients. Cavo-tricuspid isthmus line ablation was performed in 12 % of patients, and other radiofrequency (RF) touch-up ablations were performed in 17 % of subjects during the index procedure (Table 4). Minimum oesophageal temperature was achieved during cryoapplication most often in LIPV (26 %), followed by LUPV (26 %) and RIPV (24 %). However, the lowest numerical values were observed during LCV cryoapplication (27.78, SD 1.72 °C). Mean Cryoballoon application duration for LUPV, LIPV, LCV, RUPV and RIPV are 273s, 210s, 333s, 190s and 185s, respectively. Mean time-to-isolation (PV potential disappearance during cryoballon application) for LUPV, LIPV, LCV, RUPV and RIPV are 44s, 46s, 41s, 37s and 43s, respectively. Nadir temperature during cryoapplication was usually less than −40 °C in all veins. Atrial arrhythmia at the beginning of the procedure was noted in as high as 44 % of the cohort. Atrial arrhythmia persisted after the procedure in 21 % of the cohort for which electrical cardioversion was done. All patients were in sinus rhythm after cardioversion. The occurrence of atrial arrhythmia at the beginning (88 % vs 30 %, P < 0.01) and persistent arrhythmia after the procedure requiring cardioversion (69 % vs 6 %, P < 0.01), both were significantly higher in the persistent AF group.

• •Safety

Table 3.

Procedural characteristics.

Procedural characteristics	Total cohort (N = 66)	Paroxysmal AF (N = 50)	Persistent AF (N = 16)	P- Value
Prior Radiofrequency ablation (N [%])	6 (9.09)	5 (10.00)	1 (6.25)	0.548
Ablation tools
28 mm Cryoballoon (N [%])	66 (100)	50 (100)	16 (100)	NA
Arctic Front Advance (N [%])	66 (100)	50 (100)	16 (100)	NA
Achieve Mapping Catheter	66 (100)	50 (100)	16 (100)	NA
Left atrial dwell time in minutes (mean ± SD)	60.80 (19.28)	62.76 (20.09)	54.68 (15.51)	0.146
Total fluoroscopy time in minutes (mean ± SD)	40.17 (16.97)	39.44 (15.47)	42.43 (21.42)	0.543
General Anaesthesia (N [%])	66 (100)	50 (100)	16 (100)	NA
Intra‐procedural 3D electroanatomical mapping (N [%])	66 (100)	50 (100)	16 (100)	NA
Intracardiac echocardiography (N [%])	17 (25.76)	13 (26.00)	4 (25.00)	0.608
Oesophageal temperature monitoring (N [%])	66 (100)	50 (100)	16 (100)	NA
Minimum oesophageal temperature Frequency (N [%])
LUPV	17 (25.76)	13 (26.00)	4 (25.00)	0.787
LIPV	22 (33.33)	16 (32.00)	6 (37.50)
LCV	6 (9.09)	6 (12.00)	0 (0)
RUPV	4 (6.06)	3 (6.00)	1 (6.25)
RIPV	16 (24.24)	11 (22.00)	5 (31.25)
RMPV	1 (1.52)	1 (2.00)	0 (0)
Minimum oesophageal temperature observed degree C (mean ± SD)
LUPV	31.45 (2.28)	31.43 (2.36)	31.5 (2.34)	0.392
LIPV	29.72 (3.01)	29.92 (3.21)	29.21 (2.60)
LCV	27.78 (1.72)	27.78 (1.72)	N/A
RUPV	33.42 (1.23)	33.36 (1.50)	33.6 (0)
RIPV	30.36 (3.43)	31.17 (3.45)	28.6 (2.94)
RMPV	33.6 (0)	33.6 (0)	N/A
Phrenic nerve monitoring
Pacing/Palpate	66 (100)	50 (100)	16 (100)	NA
Diaphragm stimulation	66 (100)	50 (100)	16 (100)	NA
CMAP	66 (100)	50 (100)	16 (100)	NA
Pulmonary vein Isolation
Pulmonary vein Isolation +	19 (28.78)	12 (24)	7 (43.75)	0.129
CTI	8 (12.12)	4 (8.00)	4 (25)	0.142
Others	11 (16.66)	8 (16.00)	3 (18.75)
PV (all) potential disappearance during Cryoapplication (N [%])	24 (36.36)	18 (36.00)	6 (37.50)	0.914
Cryoballoon application time (second; mean ± SD)
LUPV	272.66 (115.73)	270.88 (105.95)	278.53 (148.47)	0.836
LIPV	209.48 (60.36)	208.97 (64.65)	211 (47.39)	0.917
LCV	332.6 (125.33)	346.57 (120.01)	300 (158.74)	0.619
RUPV	189.59 (61.02)	197.08 (61.76)	166.18 (53.87)	0.077
RIPV	184.77 (60.96)	185.04 (59.69)	183.93 (66.81)	0.950
Time-to-Isolation (second; mean ± SD)
LUPV	44.13 (18.67)	46.3 (19.35)	36 (13.94)	0.168
LIPV	46.27 (31.50)	49.71 (33.08)	28.5 (11.31)	0.133
LCV	40.55 (24.47)	45.71 (8.92)	22.5 (24.74)	0.262
RUPV	37.43 (24.44)	39.02 (26.62)	32 (24.44)	0.430
RIPV	42.72 (25.70)	41.83 (26.57)	45.4 (25.70)	0.709
ADDITIONAL VEIN	27.80 (8.78)	27.80 (8.78)	NA	NA
Nadir temperature in degree Celcius (mean ± SD)
LUPV	−47.25 (6.23)	−46.55 (6.08)	−49.53 (6.42)	0.132
LIPV	−44.06 (4.91)	−43.71 (4.35)	−45.07 (6.39)	0.393
LCV	−49.97 (10.85)	−51.71 (11.55)	−45.9 (9.71)	0.470
RUPV	−48.46 (5.91)	−48.02 (5.77)	−49.87 (6.32)	0.278
RIPV	−46.71 (6.99)	−46.88 (6.87)	−46.18 (7.56)	0.733
Atrial arrhythmia at the beginning of the procedure (N [%])	29 (43.94)	15 (30.00)	14 (87.50)	<0.001
Atrial arrhythmia at the end of the procedure (N [%])	14 (21.21)	3 (6.00)	11 (68.75)	<0.001

LUPV- left upper pulmonary vein, LIPV- left inferior pulmonary vein, LCV- left common pulmonary vein, RUPV- right upper pulmonary vein, RIPV- right inferior pulmonary vein, RMPV- right middle pulmonary vein, CTI- cavotricuspid isthmus.

Table 4.

Additional radiofrequency ablation.

PVI +	No (19)	Recurrence
CTI	8 (PAF 4, PsAF 4)	1 (PsAF)
Left Carinal ablation	3 (PAF)	0
RIPV	2 (PAF 1, PsAF 1)	1 (PsAF)
RUPV	1 (PAF)	0
Mitral Isthmus	1(PAF)	0
Posterior LA	1(PsAF)	1 (PsAF)
LA roof	1 (PsAF)	0
Anterior LA flutter	1 (PAF)	1 (PAF)
Coronary Sinus Tachycardia	1 (PAF)	0

LA-left atrium, pulmonary vein, RUPV- right upper pulmonary vein, RIPV- right inferior pulmonary vein, RMPV- right middle pulmonary vein, CTI- cavotricuspid isthmus; PAF – paroxysmal atrial fibrillation; PsAF – persistent atrial fibrillation.

In the 66 subjects included in the procedure analysis cohort, two serious procedure-related events (3.03 %) occurred. No pericardial effusion or major access site complications were observed. Two subjects (3 %) experienced phrenic nerve injury (PNI) that persisted at discharge; however, this resolved completely by the three-month follow-up visit. Both cases resulted from ablation of right superior pulmonary vein. No procedure-related strokes or transient ischemic attacks occurred. A complete list of serious adverse events is provided in Supplementary Table 2. There was one death on follow-up due to non-cardiac illness. The left inferior and right inferior pulmonary veins are particularly susceptible to a fall in oesophageal temperature below 30 °C, with the least observed in the left common pulmonary vein.

• •Efficacy

Freedom from recurrence of atrial arrhythmia at 12 months was 71 % (95 % CI 55–81 %), with a significant difference between PAF 84 % (95 % CI 68–92 %) and PsAF PAF 34 % (95 % CI 10–60 %) groups. (Fig. 2, Fig. 3). Although taking a cut-off of LA dimension 40 mm did not differ in outcome, an incremental association was found between dilated LA and atrial arrhythmia recurrence. (Supplementary Fig. 1). Presence of atrial arrhythmia at the beginning of the study (87 % vs 51 %) and failure to terminate after completion of ablative procedure, requiring electrical cardioversion, impose a higher risk (83 % vs 28 %) of recurrence (Fig. 4, Fig. 5). No difference was found between PVI and PVI + groups (Supplementary Figs. 2 and 3).

Fig. 2.

Kaplan – Meyer 12-month estimate of freedom from atrial arrhythmia (AF/AT/AFL) recurrence.

Fig. 3.

Kaplan – Meyer 12-month estimate of freedom from atrial arrhythmia (AF/AT/AFL) recurrence in PAF and PsAF groups.

Fig. 4.

Kaplan – Meyer 12-month estimate of freedom from atrial arrhythmia (AF/AT/AFL) recurrence in terms of comparison between atrial arrhythmia at the beginning of the study vs sinus rhythm at the beginning of the study.

Fig. 5.

Kaplan – Meyer 12-month estimate of freedom from atrial arrhythmia (AF/AT/AFL) recurrence in terms of comparison between atrial arrhythmia at the end of the study requiring electrical cardioversion vs sinus rhythm at the end of the study.

4. Discussion

To our knowledge, this cohort represents the first and largest assessment of an Indian population undergoing cryoballoon ablation for AF treatment, with a 12-month follow-up. Cryoablation in this diverse cohort of patients with PAF and PsAF was performed safely, with a 3.03 % rate of procedure-related serious adverse events (phrenic nerve injury). Freedom from recurrence of atrial arrhythmia at 12 months was significantly higher in PAF cohort compared to PsAF. Higher recurrence rates in persistent AF may be due to an advanced disease process and substrate.

Consistent with findings from controlled clinical trials, patients with PsAF in this study exhibited baseline characteristics indicative of more advanced AF disease, including greater left atrial (LA) dilation, reduced left ventricular function, and increased amiodarone use, compared to patients with PAF [5,6]. Regardless of AF classification, standard-of-care treatment resulted in a consistent and efficient procedure, with an average total LA dwell time of 61 ± 19 min. Specifically, a PVI-only approach was frequently employed (71 %) for both PAF and PsAF patients, reinforcing the essential role of PVI in treating all forms of AF [7]. PVI + group had predominantly reentrant flutter (e.g. CTI dependent, mitral isthmus, anterior/posterior LA reentrant flutter), focal atrial tachycardia (usually pulmonary vein origin), or incomplete total electrical isolation of pulmonary veins from LA. While previous studies have reported shorter procedural times with conscious sedation, general anaesthesia was used in all patients in this study, aligning with initial cryoablation studies and mitigating procedural challenges during the initial phase of experience in this region [8]. The use of conscious sedation is expected to increase in the future. Similarly, preprocedural CT imaging and intraprocedural electroanatomical mapping were performed in all patients. Intracardiac echocardiography (ICE) use (26 %) was primarily limited to the initial phase of experience and in challenging cases (e.g., difficult transseptal puncture or ruling out left atrial appendage (LAA) thrombus) [9]. The ability to perform effective cryoballoon ablation with minimal adjunctive tools is a challenge, particularly in resource-constrained environments, given the increasing AF patient population. Future improvements in this area are anticipated.

The overall major procedure-related side effect rate (3.03 %) was numerically lower than that reported in recent global studies [[4], [5], [6],[10], [11], [12]]. Previous studies have also documented low rates of cardiac tamponade/pericardial effusion following cryoballoon ablation, and this study further corroborates the low risk of this event in typical clinical practice. Importantly, no procedure-related deaths were reported in this registry, signifying an improvement in the safety of atrial fibrillation ablation procedures since the 2010 survey by Cappato et al., which reported a 0.15 % procedure-related mortality rate [13].

Freedom from recurrence of atrial arrhythmia at 12 months was 71 % (95 % CI 55–81 %), with a significant difference between PAF 84 % (95 % CI 68–92 %) and PsAF PAF 34 % (95 % CI 10–60 %) groups. This outcome in PAF is in concordance with one of the latest global AF registries [14]. The relatively inferior outcome in terms of recurrence observed in patients with persistent atrial fibrillation (PsAF) may be attributed to the fact that a significant proportion of chronic patients with long-standing AF have undergone ablation with the advent of newer cryoablation technology. Although a cut-off of 40 mm for left atrial (LA) dimension did not reveal a significant difference in outcome, an incremental association between LA dilatation and atrial arrhythmia recurrence was observed. This finding supports the notion of progressive atrial remodelling, which has been previously established in the literature.

The presence of atrial arrhythmia at the beginning of the study (87 % vs. 51 %) and the failure to terminate atrial arrhythmia following the ablation procedure, necessitating electrical cardioversion, were associated with a significantly higher risk of recurrence (83 % vs. 28 %). This likely reflects the chronic and resistant nature of the disease, which exhibits an intrinsic propensity for recurrence due to established disease substrate.

5. Conclusions

This study demonstrates the robust safety, efficacy, and efficiency of the cryoablation procedure across a diverse patient population with recurrent symptomatic AF. 12-month atrial arrhythmia-free survival rates were significantly higher in patients with paroxysmal AF compared to those with persistent AF. Pre-procedural atrial arrhythmias and post-cryoablation atrial arrhythmias requiring cardioversion predicted a higher risk of recurrence. Major procedural adverse effects were comparable to those reported in the Western literature.

6. Limitations

This was a retrospective, non-randomised, single-centre observational study. Patient selection bias, symptom and ECG guided recurrence assessment, and unavailability of extended wearable monitoring data for all patients a limitations. However, this study provides valuable insights into the real-world clinical experience of patients and providers in a low-middle-income country for cryoablation of atrial fibrillation.

Patient consent for publication

Obtained.

Data availability statement

Data available on request from authors.

Ethical approval statement

Not applicable.

Permission to reproduce material from other sources

Not applicable.

Author contribution

All authors (Conceptualization: Equal; Formal analysis: Lead; Writing – review & editing: Lead).

Clinical trial registration

Not applicable.

Funding

Nil.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

List of Abbreviations

1. ACC

American College of Cardiology

2. ACEi

Angiotensin-converting enzyme inhibitor

3. AF

Atrial fibrillation

4. AFL

Atrial Flutter

5. AHA

American Heart Association

6. AT

Atrial Tachycardia

7. CT

Computed tomography

8. CTI

Cavo-tricuspid Isthmus

9. DOAC

Direct oral anticoagulant

10. EF

Ejection fraction

11. ESC

European Society of Cardiology

12. HCM

Hypertrophic cardiomyopathy

13. HF

Heart failure

14. HFpEF

HF with preserved ejection fraction

15. HFrEF

HF with reduced ejection fraction

16. HRS

Heart Rhythm Society

17. LCV

Left common pulmonary vein

18. LIPV

Leftt inferior pulmonary vein

19. LUPV

Left upper pulmonary vein

20. NT-proBNP

N-terminal pro-B-type natriuretic peptide

21. PAF

Paroxysmal atrial fibrillation

22. PsAF

Persistent atrial fibrillation

23. PVI

Pulmonary vein isolation

24. RIPV

Right inferior pulmonary vein

25. RUPV

Right upper pulmonary vein

26. SGLT2i

Sodium Glucose Transporter 2 inhibitor

27. TTI

Time-to-isolation

28. VKA

Vitamin K antagonist

Appendix A. Supplementary data

The following is the Supplementary data to this article.