Safety, Efficacy, and Mid-Term Outcomes of Pulsed Field Ablation for Cavotricuspid Isthmus–Dependent Flutter: Real-World Data From a Major Health System Registry

Abstract

BACKGROUND:

Cavotricuspid isthmus (CTI) ablation is frequently performed either as a standalone procedure or in combination with pulmonary vein isolation. With the rapid adoption of pulsed field ablation for atrial fibrillation, it is essential to delineate the utility of this modality in treating CTI-dependent atrial flutter (AFL). This study aims to evaluate the procedural and clinical outcomes of CTI ablation using pulsed field energy.

METHODS:

We conducted a retrospective analysis of consecutive patients who underwent pulsed field ablation for CTI-dependent AFL between January 2024 and March 2025. The primary end points were acute procedural success, periprocedural complications, and CTI-dependent AFL recurrence during follow-up.

RESULTS:

A total of 132 patients underwent CTI nonthermal ablation. The median age was 69.5 years, and 27.3% were female. The Farawave catheter was used in 93.9% of cases, PulseSelect in 4.5%, and Sphere-9 in 1.5%. Acute block was achieved in 99.2% of patients, although 8 required adjunctive radiofrequency ablation to complete the line. Periprocedural complications included transient ST-segment elevation in 2 patients and transient conduction disturbances in 3. During a median follow-up of 114 days (n=131), 5 patients (3.8%) experienced recurrence of typical AFL. The 6-month typical AFL-free survival estimate was 93.6%.

CONCLUSIONS:

Pulsed field ablation appears to be a feasible and effective strategy for CTI-dependent AFL. However, anatomic variability may limit its universal applicability with current catheter designs. Although acute procedural success is high, the long-term durability of the CTI block and its comparative efficacy versus conventional thermal ablation remain areas requiring further investigation.

WHAT IS KNOWN?

• Cavotricuspid isthmus ablation is often required during pulmonary vein isolation for atrial fibrillation to treat coexisting cavotricuspid isthmus–dependent atrial flutter.

• Pulsed field ablation adoption is rising, but the need to switch to thermal ablation in some cases remains unclear.

• Cavotricuspid isthmus ablation is challenging due to proximity to the right coronary artery and risk of pulsed field ablation–induced coronary vasospasm.

• Acute cavotricuspid isthmus block rates with pulsed field ablation are high, but long-term durability is not well established.

WHAT THE STUDY ADDS

• Largest real-world registry of cavotricuspid isthmus–dependent atrial flutter treated with pulsed field ablation, showing low complication rates, mostly transient, including ST-segment elevation.

• Typical atrial flutter recurrence was low, comparable to previously published data from thermal ablation, demonstrating mid-term durability of cavotricuspid isthmus block.

• Anatomic variability may limit the universal applicability of current pulsed field ablation catheters, sometimes requiring additional maneuvers or conversion to radiofrequency ablation.

Pulsed field ablation (PFA) is a novel, nonthermal ablation modality that employs high-voltage, short-duration electrical pulses to induce irreversible electroporation, selectively targeting myocardial tissue. Recently approved by the US Food and Drug Administration for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF), PFA offers several advantages over traditional thermal techniques, including tissue selectivity and reduced collateral injury. In patients undergoing PVI for AF, additional cavotricuspid isthmus (CTI) ablation is often warranted to address coexisting CTI-dependent atrial flutter (AFL).

Emerging data suggest that PFA provides outcomes comparable to conventional thermal energy sources for AF ablation.¹ However, CTI ablation poses unique challenges due to its anatomic proximity to the right coronary artery and the potential for PFA-induced coronary vasospasm.² Although clinically significant vasospasm with ST-segment elevation appears to be rare,³ subclinical vasospasm—detected via angiography—has been reported with high frequency, even in patients receiving prophylactic nitrates.^4,5

Although acute procedural success with PFA in CTI ablation has been acceptable, the long-term durability of CTI block using this technology remains uncertain.³ This study aims to evaluate the procedural efficacy and mid-term outcomes of PFA for CTI-dependent AFL through a retrospective analysis of patients treated with pulsed field (PF) energy.

Methods

The data that support the findings of this study are available from the corresponding author on reasonable request.

Study Design and Patient Population

This is an observational retrospective study that included consecutive patients who underwent CTI ablation using PFA at the 3 major Mayo Clinic campuses in the United States (Phoenix, AZ; Jacksonville, FL; and Rochester, MN) from January 2024 to March 2025. Patients under the age of 18 years and patients who only received radiofrequency lesions on the CTI were excluded from our study. The first CTI ablation using PFA was considered the index procedure. Patients were identified through electronic health records, and manual chart review was performed for patients who met the inclusion criteria. Baseline data, procedural characteristics, and outcomes of the ablation were extracted and collected for statistical analysis. This study was conducted with approval from the institutional review board of our institution.

Procedure Characteristics

All patients were brought to the electrophysiology laboratory after obtaining informed consent. Patients underwent general anesthesia, and intracardiac catheters were advanced through the right femoral vein and placed under fluoroscopic guidance and 3-dimensional mapping systems (NavX [Abbott], CARTO [Biosense Webster], and Affera [Medtronic]). A decapolar catheter was placed in the coronary sinus to provide stable reference electrograms, whereas an intracardiac echocardiography catheter was used to create an anatomic map and facilitate catheter positioning. Transeptal puncture was achieved as previously described.⁶ Continuous heparinized saline flush was maintained through the sheath to maintain activated clotting time of >300 s throughout the procedure with periodic monitoring. PVI and additional left atrial targets, at the discretion of the operator, were performed using one of the PFA catheters: Farawave, PulseSelect, or Sphere-9.

CTI ablation was performed at the operator’s discretion. The main indications included previously documented typical flutter or typical flutter induced during the procedure. Entrainment and pacing maneuvers were performed to induce AFL and identify the circuit, after which the catheters were withdrawn into the right atrium on detection of CTI-dependent flutter. Preemptive nitroglycerin and glycopyrrolate were given based on operator preference. The ablation catheter was then placed along the CTI, and energy was delivered to the CTI to achieve ablation. On delivery of the energy, CTI line was checked for bidirectional block using differential pacing and transisthmus conduction times. Finally, intracardiac echocardiography was utilized to check for pericardial effusion. All catheters were withdrawn at the end of the procedure (Figure 1).

Figure 1.

Pulsed field ablation (PFA) for cavotricuspid isthmus (CTI)–dependent flutter. A, Baseline right atrial voltage mapping. B, Post-PFA right atrial voltage mapping demonstrating elimination of all local signals along the CTI. C, right anterior oblique fluoroscopic view showing the pentaspline catheter in the flower configuration positioned on the CTI. D, left anterior oblique fluoroscopic view showing the pentaspline catheter in the basket configuration on the Eustachian ridge. E, Surface ECG and intracardiac electrograms demonstrating atrial flutter termination after pulsed field energy delivery.

End Points and Follow-Up

The primary end points were defined as acute procedural success and typical AFL recurrence during follow-up. Acute procedural success was defined as the achievement of bidirectional conduction block across the CTI at the end of the ablation procedure. Secondary end points included procedural complications, atypical AFL recurrence, and repeat ablation procedures. Atypical AFL recurrence was defined as any electrocardiographically documented recurrence without characteristics of clockwise or counterclockwise CTI-dependent flutter, according to the evaluation of 2 experienced electrophysiologists.

A standardized follow-up strategy was implemented, consisting of clinic visits at 1, 3, 6, and 12 months, with a 12-lead ECG performed at each visit, 3-month Holter monitoring, and, when applicable, device interrogations. Additional monitoring was performed at the discretion of the treating physician based on the occurrence of symptoms. Data from emergency room visits were also collected. Complications were categorized as CTI ablation specific if there was a direct association between the ablation in this area and the event. Other complications, such as vascular access complications, transseptal puncture complications, stroke, and phrenic nerve palsy, were classified as non-CTI ablation specific.

Statistical Analysis

Continuous variables are presented as medians (interquartile range), and categorical variables are presented as absolute and relative frequencies. Survival analyses were conducted using Kaplan-Meier curves, and 95% CI were reported. Statistical analyses were performed with R statistical software (version 4.2.3; R Foundation for Statistical Computing, Vienna, Austria).

Results

To the best of our knowledge, this is the largest real-world study reporting data on CTI ablation using PF energy. The patients’ baseline characteristics are summarized in Table 1. Overall, 132 patients were included for review. The median age was 69.5 years, and 27.3% were female. The median CHA₂DS₂-VASc score was 3 (2–4). The median left ventricular ejection fraction was 58% (52%–62%), and the median left atrial volume index was 39 mL/m² (33–45 mL/m²). Hypertension (72.7%), obstructive sleep apnea (36.4%), and congestive heart failure (30.3%) were the most common comorbidities. Eighty-one patients (61.4%) had paroxysmal AF, and 51 (38.6%) had persistent AF. Typical AFL was documented in 92 patients (69.7%) before the procedure, whereas in 40 patients (30.3%), typical AFL was induced during the procedure without previous documentation. Thirty patients had a history of prior PVI, and 12 patients had undergone CTI ablation.

Table 1.

Baseline Characteristics

The median total procedure time, including CTI and additional targets, was 160 minutes (136–208 minutes). The Farawave catheter was used in 124 patients (93.9%), the PulseSelect in 6 patients (4.5%), and the Sphere-9 in 2 patients (1.5%). The 2 patients who underwent CTI ablation with the Sphere-9 catheter received radiofrequency ablation (RFA) and PFA. Ten patients required the combined use of RFA and PFA for the CTI block. In 8 of those patients, PFA was the first-choice energy source, whereas in the other 2, radiofrequency was the first choice. The Sphere-9 dual-energy catheter was used for both patients in whom RFA was transitioned to PFA. Among patients who underwent PFA alone for CTI ablation, the median number of PF applications was 10 (7–12). For the Farawave catheter, the median number of applications was 10 (interquartile range, 6–12). For the PulseSelect catheter, the median number of applications on the CTI was 10 (interquartile range, 6–15.5). Regarding the Sphere-9 catheter, 1 patient required 2 PFA applications and 6 radiofrequency applications, whereas the other required 1 PFA application and 35 radiofrequency applications. Prophylactic nitroglycerin and glycopyrrolate were administered to 23 patients (46%) and 45 patients (34%), respectively.

Acute CTI bidirectional block was demonstrated in 131 patients (99.2%). In the only case where bidirectional block was not confirmed, extensive ablation was performed across the CTI, effectively eliminating all local signals. Remapping did not reveal any clear breakthrough; however, a very late signal was noted on the lateral aspect of the CTI, suggestive of medial-to-lateral block. Despite this, local capture could not be achieved at that site to definitively confirm bidirectional block. For patients who had PFA as the first-choice energy source, a CTI bidirectional block was achieved with PFA alone in 122 of 130 patients (93.8%). Detailed procedural characteristics are presented in Table 2. For example, of post-CTI ablation voltage and activation mapping are presented in Figure 2.

Table 2.

Procedure Characteristics

Figure 2.

Postablation voltage and activation mapping. A, Preablation voltage map showing FaraWave catheter delivery locations. B, Postablation voltage map showing FaraWave catheter delivery locations. C, Cavotricuspid isthmus (CTI) activation showing medial-to-lateral conduction block after pulsed field ablation (PFA) with FaraWave catheter. D, Low voltage along CTI after PFA with FaraWave catheter. E, CTI activation showing medial-to-lateral conduction block after PFA with PulseSelect catheter. F, Low voltage along CTI after PFA with PulseSelect catheter.

The reasons patients required additional RFA were as follows: 1 patient experienced hypotension after the first CTI PF delivery; 1 patient developed left bundle branch block (LBBB) after the first CTI PF delivery; 1 patient had 2:1 atrioventricular block after the first CTI PF delivery; 3 patients had challenging anatomy resulting in suboptimal catheter contact; and 2 patients exhibited persistent CTI conduction despite PF ablation (Figure 2).

No periprocedural deaths occurred. One patient with a CHA₂DS₂-VASc score of 3 experienced a major non-CTI–specific complication: a presumed thromboembolic stroke. The ablation was performed with the Sphere-9 catheter. Past medical history included hypertension, peripheral vascular disease, emphysema, obstructive sleep apnea, coronary artery disease, hyperlipidemia, former smoker status, and unprovoked deep vein thrombosis. She was anticoagulated with rivaroxaban, which was not held before the procedure.

CTI ablation–specific complications were observed in 6 patients, including 1 transient LBBB (Figure 3A and 3B), 2 transient atrioventricular blocks (Figure 3C and 3D) and 2 cases of transient ST-segment elevation after CTI ablation. Glycopyrrolate was prophylactically administered to the patient who developed transient LBBB, but not to the patients who developed transient atrioventricular block. Both ST-segment elevations occurred in patients who did not receive prophylactic nitroglycerin. In the first case, delayed ST-segment elevation in the inferior leads appeared after 10 PFA deliveries on the CTI and a total of 48 deliveries overall. This was promptly treated with an intravenous bolus of nitroglycerin (200 µg), resulting in immediate resolution of the ST-segment elevation. In the second case, the CTI block was achieved after 12 PF deliveries. Thirty seconds after completion, the patient developed inferior ST-segment elevations and runs of ventricular tachycardia. An IV lidocaine bolus was administered, and both the ST elevations and ventricular tachycardia spontaneously resolved within 6 minutes. Coronary angiography of the left and right coronary arteries showed normal vessels without evidence of active vasospasm. The distribution of complications is reported in Table 3.

Figure 3.

Conduction disturbances after pulsed field (PF) deliveries on the cavotricuspid isthmus (CTI). A, Left bundle branch block (LBBB) after the first PF delivery on the CTI. B, Resolution of LBBB after 7 s. C, 2:1 atrioventricular (AV) block after the first PF delivery on the CTI. D, Resolution of 2:1 AV block after 30 s.

Table 3.

Complications

We identified 8 patients with anatomic variations that made CTI ablation more challenging. Three patients had a prominent Eustachian ridge, 2 had a deep sub-Eustachian pouch, 1 had a narrow isthmus, 1 had heavy trabeculations, and 1 had a deep sub-Eustachian pouch, a prominent Eustachian ridge and a Chiari network (Table 4).

Table 4.

CTI Challenging Morphology

For the patients with a prominent Eustachian ridge, bidirectional block was achieved using the Farawave catheter in 2 cases, employing a superior approach with inferior orientation and delivering PFA applications in both the basket and candy-cane configurations. In the remaining case, adequate contact could not be achieved; therefore, a Thermocool radiofrequency catheter was advanced, and a bidirectional block was achieved after creating a linear lesion.

For one of the patients with a deep sub-Eustachian pouch, a CTI bidirectional block was achieved using the Farawave catheter in the flower configuration, whereas in the other patient, a complete block could not be confirmed despite the use of both PFA with the Farawave catheter and additional RFA with an irrigated-tip catheter.

In the case of the patient with a narrow isthmus, the Farawave catheter could not be engaged perpendicularly to the CTI; therefore, a parallel orientation was used, delivering 8 applications in flower configuration, but no block was achieved. Subsequently, an irrigated radiofrequency catheter was advanced, and a complete bidirectional block was achieved after creating a linear lesion in the middle portion of the CTI.

In the patient with a combination of a deep sub-Eustachian pouch, a prominent Eustachian ridge, and a Chiari network, the Farawave catheter in the flower configuration achieved bidirectional block after ablation along the entire isthmus, including the deep pouch and extending to the tip of the Eustachian ridge.

Interestingly, for the patient with heavy trabeculations, the initial approach was RFA of the CTI using the Sphere-9 catheter. However, a bidirectional block was not achieved, and a single PFA application with the same catheter resulted in a complete block.

Follow-up data were available for 131 patients, with a mean follow-up of 114 days (91–161.5 days) and a 73% compliance rate with the 3-month Holter ECG. Typical AFL recurrences occurred in 5 patients (3.8%), and atypical AFL was also observed in 13 patients (9.9%). The 6-month typical AFL-free survival estimate was 93.6% (95% CI, 87.8–99.9%; Figure 4).

Figure 4.

Kaplan-Meier curves. A, Kaplan-Meier survival curve for typical atrial flutter (AFL) event–free survival. The estimated 180-day event-free survival was 93.6% (95% CI, 87.8%–99.9%). B, Kaplan-Meier survival curve for any AFL event-free survival. The estimated 180-day event-free survival was 82.1% (95% CI, 73.7%–91.4%).

During follow-up, 5 patients underwent repeat atrial arrhythmia ablation. In 3 of them, the CTI bidirectional block persisted; however, in 2 patients, CTI reconnection was documented, requiring additional RFA. Notably, one of these patients had no documented typical AFL recurrence at the time of the repeat procedure (Table S1).

A detailed analysis of procedural characteristics, complications, and follow-up by the PFA platform is presented in Table S2.

Discussion

Our study provides important insights into the use of PFA for CTI-dependent AFL. The main findings are as follows:

1. PFA for CTI ablation is feasible and demonstrates a high rate of acute procedural success. When considering all patients—regardless of the need for additional RFA—an acute bidirectional CTI block was achieved in 99.2%. However, when PFA was used as the sole energy source, the acute success rate was 93.8%.

2. Despite achieving an acute CTI block, recurrence of typical AFL occurred in 3.8% of patients over a median follow-up of 114 days.

3. Anatomic variations in the CTI region may limit the efficacy of PFA alone, necessitating adjunctive energy delivery in select cases.

PFA demonstrated encouraging procedural efficacy, with acute success rates comparable to those of traditional thermal techniques. When used as a first-line modality, PFA alone achieved acute bidirectional block in 93.8% of cases, underscoring its promise as an effective treatment option. These findings align with the known benefits of PFA, including myocardial selectivity, rapid lesion formation, and a favorable safety profile.

Compared with RFA, particularly when guided by lesion-index metrics, PFA appears similarly effective. For instance, the FLAI study reported a 98.3% acute success rate using ablation index–guided RFA across 405 patients.⁷ Similarly, published PFA studies have shown acute bidirectional block rates of 98.6% to 100%.^8–10

In our cohort, the median number of PFA applications required for CTI ablation was 10 (interquartile range, 6–12), highlighting the technical complexity of linear lesion creation. Effective catheter contact, optimal positioning, and adequate lesion overlap are essential for procedural success. The need for adjunctive radiofrequency energy in anatomically complex cases, particularly those with deep pouches or prominent Eustachian ridges, reflects current limitations in energy delivery with existing PFA catheter designs.

Although PFA has proven highly effective for PVI, its role in non-PV targets is still evolving.^11,12 Although PFA demonstrates high acute success, its durability in CTI ablation is less well established. In our study, the 6-month typical AFL-free survival rate was 93.6%. CTI ablation presents unique challenges due to anatomic factors, including the thick muscular isthmus near the tricuspid annulus and adjacent structures, such as the Eustachian ridge. These factors complicate durable lesion formation and may contribute to conduction gaps. In addition, the phenomenon of acute conduction stunning may falsely suggest a complete block during the index procedure.^13–15

Evidence for the long-term durability of PFA in CTI ablation is still emerging. In a recent single-arm trial, 96.4% of patients undergoing CTI ablation with a focal PFA catheter achieved bidirectional block and required no further ablation during a 12-month follow-up. However, the overall recurrence rate, including those who were not reablated, was not reported. Notably, this study required the use of an additional focal catheter after initial PVI with a pentaspline system.¹⁰ In contrast, Chaumont et al⁹ reported no symptomatic flutter recurrence at 6 months after CTI ablation using a pentaspline catheter in 32 patients, though continuous monitoring was not used. Compared with these reports, our recurrence rates seem favorable but underscore the need for longer-term data to assess lesion durability.

In our study, the most commonly used catheter was the Farawave, a multielectrode array designed for PVI, utilized in both basket and flower configurations. Focal catheters such as Sphere-9, though used in a minority of cases, may be better suited for non-PV targets due to their more focused lesion delivery. Catheter configuration plays a critical role in ensuring adequate tissue contact—particularly in anatomically complex regions of the CTI.

Approximately 6.1% of our cohort exhibited challenging CTI anatomy, consistent with prior reports.² In 3 of these patients, additional RFA was required after initial PFA attempts. One case highlighted the benefit of dual-energy catheter use, wherein both RFA and PFA were delivered through a single catheter system, potentially reducing costs and procedural complexity.

Adequate contact remains a key procedural challenge in CTI ablation. Intracardiac echocardiography has emerged as a valuable tool to guide catheter positioning and assess contact in real time. Intracardiac echocardiography can improve success rates and may help overcome anatomic obstacles that limit lesion efficacy.³

Unlike PVI, CTI ablation with PFA introduces a unique safety consideration due to its proximity to the coronary vasculature. Coronary vasospasm is a recognized complication of PFA. In our cohort, 2 cases of transient ST-segment elevation occurred, both in patients who had not received prophylactic nitroglycerin. These events resolved promptly with nitrate administration. This aligns with other studies that recommend preemptive nitrates during CTI ablation using PFA.¹⁰

Importantly, although RFA can cause direct thermal damage to coronary arteries, PFA-induced vasospasm results from smooth muscle activation and typically does not produce long-term coronary injury.^16,17 Nonetheless, Tam et al¹⁸ reported coronary luminal narrowing of ≈10% on follow-up optical coherence tomography in patients undergoing PFA near the CTI or mitral isthmus, even in the absence of overt vasospasm during the index procedure. The extent of luminal narrowing correlated with procedural vasospasm, indicating potential subclinical vascular involvement.

These findings suggest heightened vigilance is necessary in patients with underlying coronary artery disease, and follow-up angiography may be warranted in cases of vasospasm.

In our population, 3 patients (3.8%) experienced transient PFA-related complications at the CTI. These included 2 cases of ST-segment elevation due to vasospasm, which resolved with nitrates; 2 cases of transient atrioventricular block; and 1 case of transient LBBB.

Interestingly, the 2 cases of atrioventricular block did not receive prophylactic glycopyrrolate, whereas the case of LBBB did. This finding highlights the role of anticholinergic drugs in preventing vagal reactions during PFA, which have previously been reported to effectively reduce such events, but also suggests additional mechanistic pathways that may affect the conduction system.¹⁹

Limitations

This study has several limitations. It is a retrospective, observational analysis, and as such, is subject to selection bias. In addition, there was no control group treated with conventional RFA, limiting direct comparative conclusions. The median follow-up duration of 114 days, while informative, is relatively short; longer-term follow-up is needed to assess the true durability of CTI block with PFA. Despite a comprehensive electrocardiographic evaluation by experienced electrophysiologists, not all patients with documented recurrences underwent repeat mapping/entrainment, which would provide a more objective assessment to confirm CTI dependence of the arrhythmia.

As this is an emerging technology recently introduced in the United States, operator experience and learning curves may have influenced outcomes. Importantly, we reported data from 3 different PFA platforms, enhancing the generalizability of the findings; however, the sample size for the PulseSelect and Sphere-9 catheters was limited, preventing analysis based on catheter type. Further studies comparing the performance of different PFA platforms for CTI ablation are warranted. Prospective, randomized studies comparing PFA with standard-of-care RFA will be essential to establish the long-term efficacy, safety, and cost-effectiveness of this novel modality.

Conclusions

PFA for CTI-dependent flutter is a feasible alternative; however, anatomic variations may limit its application. The durability of acutely confirmed CTI block and its benefit compared with standard thermal strategies remain questionable.

ARTICLE INFORMATION

Sources of Funding

This publication was supported and funded by Mayo Clinic Arizona Cardiovascular Clinical Research Center (MCA CV CRC). The authors are thankful for their generous support. Contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the MCA CV CRC.

Disclosures

None.

Supplemental Material

Tables S1–S2