This study aims to investigate predictors of LVEF improvement following AF catheter ablation in patients with HF and impaired LVEF.

We conducted a retrospective observational study of consecutive patients with HF and LVEF <50% referred for AF catheter ablation between May 2016 and May 2022 in a tertiary referral center. This study is a continuation of our prior exploratory research which included a small subset of patients.10 All patients provided written informed consent and the study followed the principles of the Declaration of Helsinki.

Adult patients referred for AF catheter ablation were eligible for inclusion in the study if they presented the following criteria: LVEF <50% and symptomatic HF. Paroxysmal AF was defined as AF that terminates spontaneously or with intervention (drugs or electrical cardioversion) within seven days. Persistent AF was defined as AF lasting beyond seven days including episodes terminated by intervention, while long-standing persistent AF was defined as continuous AF beyond 12 months with the adoption of a rhythm control strategy. Symptomatic HF was defined as the presence of signs or symptoms typically associated with HF in the presence of LVEF <50%, and the severity of symptoms was described according to the New York Heart Association (NYHA) functional classification.11 Patients with impaired LVEF were categorized into two groups: heart failure with mildly reduced ejection fraction (HFmrEF) with LVEF between 41% and 49%, or heart failure with reduced ejection fraction (HFrEF) with LVEF ≤40%.11 Significant coronary artery disease had to be ruled out by cardiac angiography or stress testing. Patients without severe valvular disease, ischemic cardiomyopathy, hypertrophic cardiomyopathy, neuromuscular disease, congenital heart disease, or other possible etiology, formed the group with suspected tachycardia-induced cardiomyopathy (TIC). To characterize the cohort, relevant data were collected from medical records. This included the echocardiogram performed on the day before ablation and at least six months post-ablation (LVEF, LV end-diastolic diameter [LVEDD], left atrial [LA] volume index) and cardiac magnetic resonance (CMR) measurements performed during the etiologic assessment of HF (LVEF, LV end-diastolic volume, LA area, and the presence of late gadolinium enhancement). Exclusion criteria were redo procedures, contraindication to anticoagulation, and the presence of intracardiac thrombus detected before the ablation procedure.

Details of the periprocedural management of AF ablation have been published previously12–14 and are described in detail in the Supplementary Data. The energy source for the procedure (cryoablation or radiofrequency [RF]) was at the discretion of the physician, as was the strategy in patients treated by RF – pulmonary vein (PV) isolation (PVI) or PVI plus ablation of low-voltage areas (these areas were ablated to achieve tissue homogenization and if necessary, lines were performed). All RF procedures were conducted under general anesthesia. In cases of previous history of typical atrial flutter, or if flutter was induced during the procedure, a cavotricuspid isthmus ablation line was also performed. If AF persisted or was inducible at the end of the procedure, electric cardioversion was performed.

The primary study goal was to determine the number of patients who recovered LVEF after AF catheter ablation and to identify predictors of LVEF improvement. Accordingly, patients were divided into ‘responders’ and ‘non-responders’ in terms of LVEF improvement.15 For patients with HFmrEF, a response was considered positive if LVEF improved to ≥50%, while for patients with HFrEF, a positive response was defined as a ≥10% increase from baseline LVEF, with LVEF reaching >40%. All patients who did not meet these criteria were categorized as non-responders.

Secondary endpoints focused on one-year effectiveness and safety data. Effectiveness was defined as freedom from any documented atrial arrhythmia lasting at least 30 s, irrespective of symptoms, after the three-month blanking period.16 Safety was defined by the occurrence of any of the following events after the index AF ablation: death, major bleeding as defined by the International Society on Thrombosis and Hemostasis,17 any thromboembolic event, atrioesophageal fistula, phrenic nerve palsy, PV stenosis, pericarditis, or vascular access complications.

We also aimed to validate the LVEF recovery prediction model proposed by Bergonti et al.18 This model takes into consideration four variables: established etiology of HF (2 points), QRS >120 ms (2 points), paroxysmal AF (1 point), and LA volume index (1 point).

After the index procedure, patients were assessed before hospital discharge and at three, six and 12 months. Each appointment included clinical evaluation, electrocardiogram, and 24-hour Holter monitoring. Seven-day Holter monitoring was performed once a year. Additionally, echocardiography was repeated at six or 12 months. No antiarrhythmic drug (AAD) was prescribed after paroxysmal AF ablation, while for persistent AF, AAD prescription was left to the physician's discretion. The first three months post-procedure were considered a blanking period and recurrences in this period were not considered. Anticoagulation therapy was maintained for the first three months and prescribed thereafter according to the CHA2DS2VASc score.19

Continuous data were described using mean±standard deviation or median and interquartile range, depending on the normality of distribution as assessed by the Kolmogorov–Smirnov test. The Student's t test or the Mann–Whitney U test was used for comparison, depending on normality. Categorical variables were presented as frequency and proportion and compared using Fisher's exact test or the chi-square test. To identify predictors of LVEF improvement, univariate and multivariate logistic regression analyses were conducted. The discriminative performance of the prediction model for LV systolic function recovery in our population was evaluated using the area under the curve (AUC) from receiver operating characteristic (ROC) analysis. Kaplan–Meier curves and the log-rank test were used to assess and compare freedom from AF recurrence during follow-up according to AF type (paroxysmal vs. persistent or long-standing persistent). Statistical significance was set at a two-sided p-value <0.05. Data analysis was performed using IBM SPSS Statistics for Macintosh software, version 20.0 (IBM).

The final study sample consisted of 100 patients (79% male, median age 60 [IQR 51–66] years). Baseline characteristics are summarized in Table 1, categorized according to type of HF. Most patients had persistent or long-standing persistent AF (71%). After the exclusion of alternative causes for HF, seventy patients were suspected of having TIC (half of them underwent CMR). Most patients were in NYHA functional class II, while one-third were in class III. Mean LVEF was 37%, with 60% of patients presenting LVEF ≤40% (Table 2). Most patients (71%) were on AADs, of which amiodarone was the most commonly used (Supplementary Table S1).

Baseline characteristics were similar between these groups (Table 1). Patients with HFrEF presented a lower prevalence of paroxysmal AF (21.7 vs. 40.0%, p=0.048) and less frequent history of coronary artery disease (11.7 vs. 0%, p=0.025), while having more severe symptoms (NYHA III) (41.7 vs. 17.5, p=0.011). There were no significant differences between groups in brain-type natriuretic peptide levels (156.5 [50.5–450.5] vs. 118.5 [(85.2–391.5] pg/ml, p=0.969). Patients with LVEF ≤40% had greater LVEDD (58±6 vs. 53±4 mm, p<0.001) but similar LA volume (47±15 vs. 44±10 ml/m2, p=0.37) compared to patients with HFmrEF (Table 2).

Table 3 provides an overview of the procedural details. Although 71% of the patients had previously undergone electrical cardioversion (those with persistent or long-standing persistent AF), only 53% were in sinus rhythm at the beginning of the procedure. Most patients (90%) underwent RF-guided ablation and 61% underwent additional ablation besides PVI. At the end of the procedure, 75% of patients were in sinus rhythm, the remainder requiring electrical cardioversion.

Most patients were discharged under AADs (51%), mainly amiodarone (28%), followed by flecainide (18%), propafenone (4%), and sotalol (1%). Medication for HF is detailed in Supplementary Table S2.

After a median follow-up of 12 (IQR 7–18) months, there was a significant improvement in LVEF (36±10 vs. 53±10%, p<0.001), with 82% of patients meeting the criteria for responders. The mean absolute increase in LVEF from baseline to the subsequent re-evaluation was 17±13%. A suspected diagnosis of TIC was associated with a substantial increase in LVEF compared to patients with other HF etiologies (21±12% vs. 9±12%, p<0.001). Patients without new episodes of atrial arrhythmia exhibited a significant improvement in LVEF compared to those who experienced recurrences during the follow-up period (22±13 vs. 14±10%, p=0.038).

The predictors of LVEF improvement following AF catheter ablation are detailed in Table 4. Multivariate analysis revealed that a suspected diagnosis of TIC rather than another HF etiology (OR 4.916 [95% CI 1.166–20.732], p=0.030), shorter QRS duration (OR 0.969 [95% CI 0.945–0.994], p=0.015) and smaller LVEDD (OR 0.893 [95% CI 0.799–0.999], p=0.049) were associated with LVEF improvement.

The mean score derived from Bergonti et al.’s prediction model18 was 1.98±1.78, with a higher score being significantly associated with a lack of LVEF improvement (3.75±1.39 in non-responders vs. 1.79±1.90 in responders (p=0.004)). Among subjects with a score ≤1, the majority (82%) were responders. In our study population, the scoring system demonstrated good ability to discriminate between responders and non-responders, as evidenced by an area under the curve (AUC) of 0.814 (0.681–0.947, 95% CI) (Figure 1).

Figure 1.

Receiver operating characteristic analysis demonstrating good discriminative power between responders and non-responders with Bergonti et al.’s scoring system18 (area under the curve [AUC] 0.814, 95% confidence interval 0.681–0.947).

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After a median follow-up of 12 (IQR 7–18) months (Figure 2), freedom from arrhythmia recurrence was observed in 86% of the patients (64% under AADs). The median time to recurrence was 7.5 (6.0–9.0) months. There was no statistically significant difference in atrial arrhythmia recurrence rate between patients with paroxysmal vs. persistent or long-standing persistent AF (11.3 vs. 20.7%, p=0.293). Among those in whom atrial arrhythmia recurred, nine patients had AF (five persistent and four paroxysmal), while the remainder presented atrial tachycardia. The most frequent strategy involved consisted of initiating or increasing the AAD dose (64.4%), while 21.4% of them underwent another catheter ablation procedure. No predictors of recurrence were identified (Supplementary Table S2).

Figure 2.

Freedom from atrial fibrillation over time. (A) Recurrence was observed in 14% of the overall cohort at 12 months of follow-up; (B) there was no significant difference in recurrence rate between patients with paroxysmal vs. persistent or long-standing persistent AF (11.3 vs. 20.7%, p=0.293). AF: atrial fibrillation.

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There were only two reported complications (vascular fistula and hematoma), both managed conservatively.

We acknowledge several limitations inherent to our work. First, this was a single-center study and therefore our results cannot be generalized to other centers. Although the sample size of our study was relatively modest, it was similar to that of other studies analyzing predictors of LVEF improvement.18,36 Larger clinical trials are required to verify our results. Second, we acknowledge that not all patients underwent CMR and therefore we might have erroneously categorized some subjects as having a suspected diagnosis of TIC. Third, we recognize that allowing patients to undergo electrical cardioversion before ablation could have affected our results. The goal was to reduce time in AF, which has an impact on AF ablation outcomes.37 Nevertheless, since echocardiographic assessment was performed on the day before ablation, the impact of this measure was limited. Fourth, we acknowledge that arrhythmia recurrence was underestimated in our study, since our assessment relied on 24-hour and seven-day Holter monitoring. However, as demonstrated in CASTLE-AF,6 perhaps more important than the arrhythmia recurrence rate is reduction in arrhythmia burden. The assessment of arrhythmia burden in our study was limited, since only 17% of patients had an implantable device, precluding a comprehensive analysis. Finally, there will always be a degree of intra- and interobserver variability in LVEF measurement. Nonetheless, LVEF continues to be the primary parameter employed to assess LV systolic function in clinical settings, providing crucial therapeutic guidance and prognostic insights across a range of cardiac conditions, including AF.38