Case series of catheter‐based arrhythmia ablation in 13 pregnant women

Abstract Background Catheter ablation is a rarely used procedure to treat arrhythmias during pregnancy. Hypothesis In the case of maternal arrhythmia during pregnancy, zero‐fluoroscopic catheter ablation is preferable to medical treatment. Methods Between April 2014 and September 2021, we examined the demographic data, procedural parameters, and fetal and maternal outcomes in pregnant women undergoing ablation at the Gottsegen National Cardiovascular Center and University of Pécs Medical School, Heart Institute. Results Fourteen procedures (14 electrophysiological studies [EPS], 13 ablations) performed on 13 pregnant women (age 30.3 ± 5.2 years, primipara n = 6) were studied. During EPS, 12 patients had inducible arrhythmias. Atrial tachycardia was confirmed in three, atrioventricular re‐entry tachycardia via manifest accessory pathway (AP) in three, and via concealed AP in one case. Atrioventricular nodal re‐entry tachycardia was confirmed in three and sustained monomorphic ventricular tachycardia in two cases. Eleven radiofrequency ablation (84.6%) and two cryoablation (15.4%) were performed. The electroanatomical mapping system was used in all cases. Transseptal puncture was performed in two cases (15.4%) due to left lateral APs. The mean procedure time was 76.0±33.0 minutes. All procedures were performed without fluoroscopy. No complications occurred. During the follow‐up, arrhythmia‐free survival was achieved in all cases, but in two patients, we used antiarrhythmic drugs (AADs) to achieve it. APGAR score was within the normal range in all cases [median (interquartile range), 9.0/10.0 (9.0–10.0/9.3–10.0)]. Conclusions Zero‐fluoroscopic catheter ablation was an effective and safe treatment option for our 13 pregnant patients. Catheter ablation may have less side effects on fetal development than the use of AADs during pregnancy.


| INTRODUCTION
Symptomatic arrhythmias during pregnancy require a complex electrophysiological approach. Out of 100 000 pregnant women, 67 are known to have arrhythmias. Supraventricular tachycardia (SVT), such as atrioventricular nodal re-entry tachycardia (AVNRT) and atrioventricular re-entry tachycardia (AVRT), is the most common arrhythmia causing clinical symptoms. However, atrial fibrillation (AF), atrial flutter, and ventricular tachycardia (VT) can also manifest during pregnancy. Persistent arrhythmias or rapid ventricular rate response may cause maternal and fetal hemodynamic deterioration.
Many patients with symptomatic arrhythmias have been successfully treated with medical therapy. However, antiarrhythmic drugs (AADs) should be used with caution because of the adverse effects on maternal and fetal life.
Fetal risks may include preterm birth, intrauterine growth retardation, small for gestational age (SGA), respiratory distress syndrome, and congenital heart disease, which occurred in 20% of pregnancies treated with specific AADs such as beta-blockers (BB), propafenone, verapamil, or amiodarone. [1][2][3] Although catheter ablation is a treatment of choice for SVT (recommendation IB), it is only recommended in pregnant patients with drug-refractory and poorly tolerated SVT (IIa C) according to the current guidelines. 4,5 Catheter ablation is not widely used in the treatment of pregnant patients because of the potential risks of the invasive procedure (anesthetic agents, thromboembolic complications, difficulty in accessing the vessel) and radiation exposure. During ablation, radiation exposure has been minimized by the development of nonfluoroscopic catheter navigation techniques. Nowadays, physicians should consider zero-fluoroscopic catheter ablation as a less risky treatment than the use of harmful AADs in this specific patient group. 1,2 The current study aimed to report on our experience to demonstrate the safety and efficacy of catheter ablation in cardiac arrhythmias during pregnancy.

| Study design and patient population
We conducted a double-center retrospective case series study. We Our patient population included 13 pregnant women who underwent 14 electrophysiological studies (EPS) and 13 catheter ablations due to highly symptomatic or therapy-refractory cardiac arrhythmias. In one patient, only EPS was performed, and, in another case, redo ablation was required. Arrhythmias included any episodes of atrial tachycardia (AT), AF, AVRT, AVNRT, premature ventricular contractions (PVC), and VT during pregnancy. Patients' symptoms were most often palpitations and less frequently chest complaints.
One patient did not have palpitations, the first symptom was the appearance of heart failure (dyspnea, lower limb edema). None of the patients had syncope.
Cardiac examination, including medical history, physical examination, 12-lead electrocardiogram (ECG), transthoracic echocardiography, 24-hour Holter recording, and cardiac magnetic resonance imaging in case of VT was recorded in these patients, preprocedurally.

| Preprocedural management and indications for catheter ablation
All patients had symptomatic tachyarrhythmias. We opted for EPS and catheter ablation because arrhythmias may negatively impact hemodynamics and, therefore, fetal development. Some arrhythmias required elective intervention and some required emergent management. Patients with severe symptoms who were admitted as emergencies required a single or multiple low-dose antiarrhythmic treatments for rate control or heart failure symptoms. In these emergency cases, telemetry monitoring was also required before the intervention. Patients admitted electively generally did not require medication before the procedure.
We chose catheter ablation because all patients included in the study had severe arrhythmia-related symptoms or drug-refractory arrhythmias. The electrophysiologists decided on the treatment plan together with the gynecologist and the cardiologist who had previously treated the patient. Patients were informed about the potential risks of procedure failure, radiation exposure, and complications before the catheter ablation. All patients have given written consent for the ablation procedure and the use of X-rays if necessary.

| EPS and catheter ablation
The EPS and ablation procedure was performed in conscious sedation. If possible, AADs were discontinued at least 2 weeks before the procedure. The access sites were the right femoral vein and the right internal jugular vein. We used the CARTO electroanatomical mapping (EAM) system or the NavX-EnSite EAM system for mapping to achieve zero-fluoroscopy procedures. Electroanatomical reconstruction of the right atrium, including critical anatomical landmarks such as the right ventricle outflow tract (RVOT), the tricuspid annulus, the His bundle region, and the coronary sinus ostium, was performed. Standard EPS was required, then other diagnostic catheters were used, such as decapolar coronary sinus catheter, quadripolar right ventricular catheter, and His catheter. In some cases, intravenous isoproterenol was used to induce arrhythmias. The anticoagulation strategy during the procedure involved the

| Follow-up
Our study included the follow-up of the patients, analysis of arrhythmia-free survival, and complete details of pregnancy, delivery, and child development. Both obstetric and neonatal outcomes were determined, including the circumstances of delivery (number of weeks of gestation, cesarean section (C-section), or per vias naturales), complications during delivery, and the birth weight, length, and APGAR score of the newborns. Birth weight was analyzed separately for those who had undergone clinically successful catheter ablation and were not taking AADs and those who had to take AADs for some reason. The two groups were compared using the Mann-Whitney U test.
The length of the follow-up depended on the time of intervention, the average follow-up period was 30.0 ± 25.0 months. We aimed to perform an outpatient visit 3 and 12 months after ablation, including a physical examination, 12-lead ECG, and Holter or transtelephonic ECG monitoring.

| Statistical analysis
In statistical analysis, data were expressed as frequencies and percentages. Continuous variables were expressed as mean ± standard deviations. A Mann-Whitney U test was used to compare groups. Statistical analysis was performed using IBM ® SPSS ® Statistics version 22. A p value less than .05 was considered significant.

| RESULTS
We collected data on characteristics of pregnant women, such as parity and gestational age at the time of the procedure, comorbidities, and valvular heart disease. We analyzed the reason for ablation, the arrhythmia diagnosed during the EPS, the used ablation technique, energy source, and EAMs, and gathered other procedural parameters and periprocedural complications. The recurrence of arrhythmias, the clinical success rate, and the need for antiarrhythmic medication was analyzed during the follow-up period. We analyzed fetal outcomes, including the gestational week at birth, mode of delivery (C-section or vaginal), birth weight, and APGAR scores. (Table 1) We studied 13 pregnant women who underwent EPS and/or catheter ablations. Table 1 shows the baseline demographic data.

| Patient characteristics
The mean age of the patients was 30.3 ± 5.2 years. Five women (38.5%) had comorbidities, including hypertension, hypothyroidism, Leiden mutation or deep vein thrombosis, gestational diabetes mellitus, and depression. Two patients (15.4%) had valvular heart disease; one patient underwent mitral valve repair surgery for papillary muscle rupture and infective endocarditis at the age of 23 years for mitral valve prolapse. Another patient with valvular heart disease had mitral valve prolapse with mild-to-moderate mitral valve regurgitation. One patient (7.7%) had heart failure with reduced ejection fraction (HFrEF), which developed at the base of tachycardia-induced cardiomyopathy. In six patients (46.2%), preoperative medications, including BB, verapamil, ivabradine, and propafenone, were used. Two patients were on ivabradine therapy before ablation, the indications were AVRT via manifest AP in one case and RVOT PVC in the other. In the first case, drug therapy could be discontinued after successful ablation. In the second case, after ablation, verapamil therapy was started as a first step, but was changed to bisoprolol and dihydralazine therapy due to heart failure symptoms. In three patients, only BB was given before ablation with

| Arrhythmia characteristics (Table 2)
All women gave their informed consent for ablation and accepted the use of X-rays if necessary. Arrhythmia characteristics are shown in Table 2 AT with a re-entry mechanism. AVRT was found in four patients  (Table 3) Procedural characteristics are shown in  The clinical outcome depended on the procedural success, the recurrence of arrhythmias, the need for medical treatment, long-term follow-up data, and complete data on pregnancy, delivery, neonatal birth characteristics such as birth weight and APGAR score, and child development. (Table 4) The acute procedural success was defined as no return of arrhythmia during the 30-minute waiting period after the procedure, and no

| Long-term follow-up
The average long-term follow-up time was 30.0 ± 25.0 months, depending on the date of the intervention. In all cases, we planned an outpatient visit of 3 and 12 months after ablation for our patients.
Seven of the 13 patients (53.9%) did not attend an outpatient visit within 1 year of catheter ablation, despite their planned appointment.
Based on the telephone interview during data collection, they were asymptomatic and therefore did not need a follow-up visit. There was no recurrence of arrhythmia in any of the pregnant women who underwent catheter ablation. However, two pregnant women (15.4%) required AAD treatment to achieve long-term freedom from arrhythmias. Routine Holter monitoring was performed in four patients (30.8%) without symptoms and no arrhythmia was found in any patient. In one case, routine transtelephonic ECG was achieved, which did not confirm any arrhythmias. Table 4 shows the patients' acute procedural success and longterm follow-up data. (Table 5) The fetal outcome included the gestational week at birth, mode of delivery, birth weight, and APGAR score in this patient population. Finally, birth weight was analyzed separately for those who underwent clinically successful catheter ablation and were not taking AADs (Group 1) and those who had to take AADs for some reason (unsuccessful procedure, n = 2; reduced ejection fraction, n = 1) (Group 2). There were 10 babies in Group 1, with an average birth weight of 3253 ± 458 g. There were three babies in Group 2.

| Fetal outcome
The first was the baby of the patient who had undergone two interventions without permanent success and was born with a birth weight of 1990 g at 34 weeks' gestation. In the second patient, despite unsuccessful VT RFA, the baby weighed 3480 g and was born at 39 weeks' gestation. In the last case presented, where reduced EF required AAD therapy, the fetus was SGA and was born by planned C-section at 860 g at 30 weeks' gestation. In Group 2, the average birth weight was 2110 ± 1314 g; the weighted average birth weight per week of birth in this group was 2225 g. The difference in average birth weight between the two groups, probably due to the small number of cases, did not show statistical significance (p > .05).
However, to indicate the trend, it may be sufficient to show the average birth weights of the two groups. The difference between APGAR score and gestational age also showed no statistically significant difference (p > .05).

| DISCUSSION
Our study has shown that SVT is the most common arrhythmia during pregnancy. Pregnant patients with persistent severe symptomatic arrhythmias require rhythm control therapy. Zero-fluoroscopic catheter ablation can offer a safe and effective way to treat pregnant women with sustained symptomatic arrhythmias.
Although patients with persistent maternal arrhythmias are relatively rare, 1  tocolysis, but to our knowledge has no effect on birth weight. BB, propafenone, and CCB were used in our study population only if necessary. The reasons for the need to use drug therapy were undetermined arrhythmia or HFrEF. In these cases, birth weight showed a lower trend than in those who had a successful ablation and did not take AADs during pregnancy, although the difference was not significant.
In pregnant patients, catheter ablation is recommended only in drug-refractory SVT (IIa C). 4 Koźluk et al. 2 found that only 0.2% of ablation procedures are performed in pregnant women. Therefore, there are few articles in the literature on this topic, and most of them are case reports of catheter ablation during pregnancy. [9][10][11][12] To the best of our knowledge, we have studied one of the largest patient populations published in the literature. 2,13 The low number of ablation procedures performed during pregnancy is probably due to the fear of using X-rays. There are two main biological effects of radiation: tissue reactions (deterministic effects) and stochastic effects, of which carcinogenicity is the most worrying. 14 There are several additional problems with X-rays during pregnancy, such as ethical issues, although radiation doses during catheter ablation can be limited to safe levels.
According to Mattsson et al., 15 17 Williams et al. 8 investigated the effects of AAD on the fetus and birth weight but did not examine the long-term development of the children.
Our case series study suggests that catheter ablation may be a safe and effective therapeutic option in a broader, well-selected patient population of pregnant women, and more studies with large number of cases are needed in the future to confirm appropriate patient selection for ablation in this specific population.

| CONCLUSIONS
Persistent maternal tachyarrhythmia is not common but is an essential topic in clinical practice, as the prevalence of maternal arrhythmias increased between 2000 and 2012. 3 Untreated maternal arrhythmias can adversely affect fetal development or, if treated with AAD, cause lower birth weight and other complications. 6,8,17 Catheter ablation is considered safe in pregnant patients in a carefully selected patient population, 8,13 but current guidelines recommend it only for symptomatic and drugrefractory maternal arrhythmias. 5 The results of our study suggest that zero-fluoroscopic ablation has several advantages over longterm antiarrhythmic drug therapy and can be performed safely with a high success rate among a well-selected population of pregnant women. However, long-term clinical outcomes and safety need to be investigated in larger cohorts, since most of the literature on this topic is based on case reports. 9-12

| LIMITATIONS
Our study is a case series of 13 pregnant patients, which is a too small study population to provide statistically relevant data about the safety and efficacy of catheter ablation procedures in pregnancy.