Abstract
Background:
Atrial fibrillation is the most common type of arrhythmia. The symptoms of atrial fibrillation not only significantly impacted quality of life but also associated with thrombotic events and heart failure, thereby increased risk of mortality. According to current guidelines, the initial treatment strategy for patients with atrial fibrillation is antiarrhythmic medication.
Objective:
This study aimed to evaluate the safety, efficacy, and procedural adaptations required for cryoablation in Vietnamese patients with paroxysmal atrial fibrillation (AF).
Methods:
Fifteen patients with paroxysmal AF underwent cryoablation using a standardized protocol. Patient characteristics, procedural parameters, and outcomes were recorded. Safety was assessed by monitoring acute complications, and procedural success was defined as complete pulmonary vein isolation (PVI) confirmed by bidirectional block.
Results:
Complete PVI was achieved in 100% of patients, with an average procedural duration of 125 ± 32 minutes and fluoroscopy time of 14 ± 8 minutes. No acute complications related to cryoablation.
Conclusion:
Cryoablation demonstrated safety and efficacy in achieving PVI for paroxysmal AF in a resource-limited setting. Larger studies with extended follow-up are required to further validate these outcomes and explore the long-term efficacy and sustainability of cryoablation techniques.
Keywords: Atrial fibrillation, cryoablation, pulmonary vein isolation, safety, efficacy
1. BACKGROUND
Atrial fibrillation is the most common type of arrhythmia, with an estimation of 60 million people affected globally as of 2020 (1). The symptoms of atrial fibrillation not only significantly impacted quality of life (2,3) but also associated with thrombotic events and heart failure, thereby increased risk of mortality (4). According to current guidelines, the initial treatment strategy for patients with atrial fibrillation is antiarrhythmic medication (5). When patients exhibit intolerance to medications or fail to control symptoms adequately, catheter ablation is recommended, particularly in instances of symptomatic recurrence of atrial fibrillation (6). Early intervention with catheter ablation significantly improves and maintains long-term management of atrial fibrillation (7, 8).
Currently, pulmonary vein isolation (PVI) is regarded as the foundational element of catheter ablation technique for atrial fibrillation (9). Radiofrequency (RF) energy is the standard energy source used in PVI, however, it often require extended procedural times to create continuous lesions from individual point ablations, as well as relying heavily on the experience of the performing physician (9). The cryoballoon ablation method had been demonstrated to offer superior advantages, including safety, effectiveness in reducing the recurrence rate of atrial fibrillation, as well as reducing procedure time and X-ray exposure (10). This method had become a strongly recommended trend in treatment guidelines and expert consensus of the European Society of Cardiology (ESC) and the American Heart Association (AHA) (11,12).
However, as cryoablation has not yet been implemented in Vietnam, there is currently no evidence regarding its efficacy or safety as an initial treatment strategy for Vietnamese patients with paroxysmal atrial fibrillation.
2. OBJECTIVE
Therefore, we conducted this study with the primary aim of preliminarily evaluating the safety and immediate outcomes of PVI using cryoablation as a first-line treatment for paroxysmal atrial fibrillation.
3. MATERIAL AND METHODS
Patient eligibility
The study was conducted on patients with paroxysmal atrial fibrillation treated at the National Heart Institute between October 2023 and December 2023. Patients were included if they were aged between 18 and 75 years, diagnosed with paroxysmal atrial fibrillation, and had an EHRA symptom score of ≥2. Exclusion criteria included a history of myocardial infarction within 3 months prior to the procedure, cardiac surgery or percutaneous coronary intervention within 3 months, or stroke within 6 months. Patients with a left atrial anteroposterior diameter >55 mm, intracardiac thrombus, or hypertrophic cardiomyopathy were also excluded. Additionally, those with coexisting arrhythmias such as second- or third-degree atrioventricular block, Brugada syndrome, or long QT syndrome, untreated hypothyroidism or hyperthyroidism, or an estimated glomerular filtration rate of <15 ml/min were not eligible for inclusion.
Ethical considerations
The study adhered to the guidelines of the Declaration of Helsinki and received approval from the Institutional Review Board of Hanoi Medical University (Decision No. 953/GCN-HĐĐĐNCYSSH-ĐHYHN, dated October 18th, 2023). Prior to participation, all patients provided written informed consent. The investigators maintained compliance with Vietnam’s regulations and Good Clinical Practice standards to ensure patient privacy and confidentiality.
Data collection
We conducted a comprehensive assessment of patient characteristics at the time of hospital admission prior to the intervention. This evaluation included: a) general demographic and clinical parameters such as age, sex, comorbidities, and current pharmacological treatments; b) atrial fibrillation-specific features, including the duration and onset of atrial fibrillation, frequency of episodes, symptomatology, and estimated thromboembolic and bleeding risks, calculated using the HASBLED and CHA2DS-VASc scoring systems; and c) detailed clinical and diagnostic findings, comprising laboratory investigations, electrocardiography, echocardiography, 24-hour Holter monitoring, and multislice computed tomography (MSCT).
The patients underwent cryoablation following a standardized protocol, which included general anesthesia and transseptal puncture performed under X-ray guidance. Due to resource limitations, advanced imaging modalities, such as transesophageal echocardiography (TEE) and intracardiac echocardiography (ICE), were not available for procedural support. During the procedure, the following parameters were recorded: pre- and post-ablation electrogram characteristics, ablation metrics (including the lowest temperature, temperature at the time of isolation, time to PVI, and balloon thaw time), total procedural duration, and fluoroscopy time.
The primary outcomes of the study were safety and immediate procedural success. Safety was assessed based on the occurrence of procedure-related adverse events, including pericardial effusion, aortic perforation, thromboembolism, interatrial septal dissection, vascular access complications, atrioventricular block, phrenic nerve injury, and left atrial-esophageal fistula formation. Immediate procedural success was defined as complete electrical isolation of the pulmonary veins, confirmed by bidirectional conduction block between the pulmonary veins and the left atrium.
Statistical analysis
Continuous variables were presented as mean values (standard deviations), or median (IQR), while categorical variables were presented as values and percentages. A p-value of 0.05 was considered statistically significant. R language version 4.3.2 was used for all analyses.
4. RESULTS
The majority of participants were male (60%), with a median age of 60 years (IQR: 53–68). The most common comorbidities were heart failure, hypertension, and diabetes mellitus, each with a prevalence of 13%. Most participants were on anticoagulants (67%) and amiodarone (47%). The mean duration of atrial fibrillation was 10 ± 12 months, with an average frequency of 6.1 ± 7.1 episodes per month. All participants were classified as low bleeding risk, while the majority (73%) were considered high risk for stroke. On 24-hour Holter monitoring, the mean number of atrial fibrillation episodes was 14 ± 21 per day. MSCT identified one case with an anatomical variation of three right pulmonary veins (Table 1).
Table 1. Participant's characteristics (n = 15). Abbreviations: AF, atrial fibrillation; ACE, angiotensin-converting enzyme; ARBs, angiotensin II receptor blockers; bpm, beats per minute; EHRA, European Heart Rhythm Association; MSCT, multislice computed tomography; SD, standard deviation; IQR, interquartile range.
| Characteristic | Result |
|---|---|
| GENERAL CHARACTERISTICS | |
| Male, n (%) | 9 (60%) |
| Age (years), median (IQR) | 60 (53, 68) |
| Comorbidities, n (%) | |
| Coronary artery disease | 1 (6.7%) |
| Heart failure | 2 (13%) |
| Hypertension | 2 (13%) |
| Diabetes | 2 (13%) |
| Dyslipidemia | 1 (6.7%) |
| Cancer | 1 (6.7%) |
| Other comorbidities | 2 (13%) |
| Medications in Use, n (%) | |
| ACE inhibitors/ARBs | 3 (20%) |
| Diuretics | 1 (6.7%) |
| Nitrates | 0 (0%) |
| Antiplatelets | 1 (6.7%) |
| Statins | 3 (20%) |
| Anticoagulants | 10 (67%) |
| Duration of atrial fibrillation (months), X ± SD | 10 ± 12 |
| Frequency of AF episodes (episodes/month), X ± SD | 6.1 ± 7.1 |
| Symptoms, n (%) | |
| Palpitations | 14 (93%) |
| Chest pain | 6 (40%) |
| Dyspnea | 4 (27%) |
| Fatigue | 6 (40%) |
| Dizziness | 4 (27%) |
| Lightheadedness | 4 (27%) |
| Syncope | 1 (6.7%) |
| EHRA Symptom Score, n (%) | |
| 2 | 12 (80%) |
| 3 | 3 (20%) |
| History of Cardioversion, n (%) | 1 (6.7%) |
| Antiarrhythmic Medications, n (%) | |
| None | 4 (27%) |
| Amiodarone | 7 (47%) |
| Bisoprolol | 2 (13%) |
| Metoprolol | 2 (13%) |
| Bleeding Risk (HASBLED), n (%) | |
| Low risk | 15 (100%) |
| High risk | 0 (0%) |
| Stroke Risk (CHA2DS-VASc), n (%) | |
| Low risk | 4 (27%) |
| High risk | 11 (73%) |
| 24-HOUR HOLTER MONITORING | |
| Mean heart rate (bpm), X ± SD | 70 ± 12 |
| AF episodes in 24 hours (n), X ± SD | 14 ± 21 |
| Longest AF episode duration (minutes), X ± SD | 133 ± 234 |
| Mean ventricular rate during AF (bpm), X ± SD | 78 ± 17 |
| Fastest ventricular rate (bpm), X ± SD | 111 ± 29 |
| Slowest ventricular rate (bpm), X ± SD | 54.8 ± 7.3 |
| Total ventricular ectopic beats (n), X ± SD | 431 ± 436 |
| Couplet ectopy, X ± SD | 1.20 ± 1.79 |
| Triplet ectopy, X ± SD | 3.4 ± 5.3 |
| Atrial tachycardia episodes (n), X ± SD | 0.60 ± 1.34 |
| MSCT FINDINGS | |
| Left atrial volume (ml), X ± SD | 51 ± 20 |
| Left superior pulmonary vein diameter (mm), X ± SD | 16.9 ± 5.2 |
| Left inferior pulmonary vein diameter (mm), X ± SD | 14.0 ± 4.0 |
| Right superior pulmonary vein diameter (mm), X ± SD | 17.27 ± 3.59 |
| Right inferior pulmonary vein diameter (mm), X ± SD | 15.1 ± 4.4 |
| Number of right pulmonary veins, n (%) | |
| 2 | 14 (93%) |
| 3 | 1 (6.7%) |
| Number of left pulmonary veins, n (%) | |
| 2 | 15 (100%) |
| Common trunk | |
| Left | 1 (6.7%) |
| Right | 0 |
All patients achieved complete PVI, with an average fluoroscopy time of 14 ± 8 minutes and a total procedural time of 125 ± 32 minutes. Only 33% of patients achieved complete PVI for all pulmonary veins with a single cryoapplication, while the majority required at least one additional application. The overall success rate of cryoapplications achieving PVI was 86%, with an average time to PVI of 51 ± 17 seconds and a total cryoapplication duration of 187 ± 55 seconds. No acute complications related to cryoballoon ablation or transseptal puncture were observed in this study (Table 2).
Table 2. Cryoablation's characteristics. Abbreviations: PVI, pulmonary vein isolation; SD, standard deviation., a Total number of patients., b Total number of cryoapplications performed.c Total number of cryoapplications achieving PVI.
| Characteristic | n | Result |
|---|---|---|
| Fluoroscopy time (minutes), X ± SD | 15a | 14 ± 8 |
| Procedural time (minutes), X ± SD | 15 | 125 ± 32 |
| Complete pulmonary vein isolation (PVI), n (%) | 15 | 15 (100%) |
| Number of additional cryoapplications, n (%) | ||
| 0 | 5 (33%) | |
| 1 | 9 (60%) | |
| 3 | 1 (6.7%) | |
| Cryoapplication site, n (%) | 73b | |
| Left superior pulmonary vein | 16 (22%) | |
| Left inferior pulmonary vein | 18 (25%) | |
| Right superior pulmonary vein | 19 (26%) | |
| Right inferior pulmonary vein | 19 (26%) | |
| Other sites | 1 (1.4%) | |
| Lowest balloon temperature (°C), X ± SD | 73 | (-49) ± 8 |
| Balloon temperature at isolation (°C), X ± SD | 73 | (-38) ± 7 |
| Time to -30°C (seconds), X ± SD | 73 | 29.6 ± 6.3 |
| Time to -40°C (seconds), X ± SD | 73 | 51 ± 28 |
| Balloon thawing time (seconds), X ± SD | 73 | 8.7 ± 4.7 |
| Applications achieving PVI, n (%) | 73 | 62 (85%) |
| Time to PVI (seconds), X ± SD | 62c | 51 ± 17 |
| Duration of cryoapplication (seconds), X ± SD | 73 | 187 ± 55 |
5. DISCUSSION
Our findings demonstrate the safety of cryoablation for PVI in patients with paroxysmal atrial fibrillation, as no procedure-related complications were reported. These results align with evidence from previous studies. A meta-analysis comprising 84 clinical trials, 34 observational studies, and 14 randomized controlled trials involving 17,592 patients (7,951 cases of cryoballoon PVI and 9,641 cases of RF PVI) showed that cryoablation significantly reduces the risk of composite complications compared to RF ablation. Specifically, cryoablation was associated with a lower risk of (1) pericardial effusion or tamponade (RR 0.438; 95% CI 0.335–0.572; p < 0.001), (2) cardiac tamponade (RR 0.582; 95% CI 0.383–0.884; p = 0.011), and (3) vascular complications (RR 0.609; 95% CI 0.482–0.770; p < 0.001) (10). Compared to RF ablation, cryoablation preserves the fundamental structure of tissues, including the fibrous and collagen cell systems. This characteristic minimizes damage to large vascular structures and the endothelium (13).
In our study, 100% of patients achieved complete pulmonary vein isolation (PVI), with an 85% success rate per cryoapplication. Using second-generation cryoballoons (CBII), our results demonstrated PVI efficacy comparable to studies utilizing third-generation cryoballoons (CBIII) (10, 14–16). In contrast, RF ablation, despite the support of three-dimensional electroanatomical mapping systems, relies on a point-by-point ablation approach. This requires precise control of energy delivery to balance effective PVI with the risk of myocardial tissue damage, making outcomes heavily dependent on the operator's experience. Cryoablation, on the other hand, utilizes a simpler technique involving balloon navigation and stable contact at the pulmonary vein ostia. Its region-based isolation principle, combined with the safer profile of cryothermal energy, allows for easier PVI with reduced concerns about procedural complications, making it more accessible for operators with varying levels of expertise.
In our study, the fluoroscopy time and total procedural time were 14 ± 8 minutes and 125 ± 32 minutes, respectively. These findings represent a significant reduction in procedure duration compared to conventional RF ablation techniques previously employed. In a 2011 meta-analysis by Andrade et al., which included 7,951 cryoablation cases and 9,641 RF ablation cases, cryoablation demonstrated a statistically significant reduction in procedure time compared to RF ablation, with a mean difference of –20.76 minutes (95% CI: –29.38 to –12.14; p < 0.001) (10). In another 2014 systematic review involving 14 clinical trials with 469 cryoablation cases and 635 RF ablation cases for atrial fibrillation, cryoablation demonstrated statistically significant improvements in both fluoroscopy time and total procedural time (17). The reduction in procedural time is critically important, as the prolonged duration of 4–6 hours required for a single RF ablation procedure often leads to catheterization lab overload. This, in turn, extends patient wait times and delays timely intervention. Such delays can severely impact the quality of life of patients and, more importantly, increase the risk of atrial fibrillation-related cardiovascular events that may arise during the waiting period, directly threatening patient safety and survival.
6. CONCLUSION
Our study demonstrated preliminary evidence supporting the safety and efficacy of cryoablation for pulmonary vein isolation in the treatment of paroxysmal atrial fibrillation in Vietnam. However, several limitations were noted, including the small sample size, the lack of long-term follow-up which restricted the understanding of ablation durability and atrial fibrillation recurrence rates, and the lack of a control group. Future studies with a control group, a larger sample sizes and extended follow-up periods, ideally lasting at least one year, was recommended to provide more comprehensive evaluations of the technique’s effectiveness, sustainability, and potential to reduce arrhythmia recurrence.
Autor's conribution:
The all authors were involved in all steps of preparation this article. Final proofreading was made by the first author.
Conflict of interest:
The authors declare no competing interests in preparing this article.
Financial support and sponsorship:
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
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