Clinical determinants of early spontaneous conversion to sinus rhythm in patients with atrial fibrillation

We conducted an observational study of 943 adult patients who visited the ED with AF between July 2014 and December 2016. Patients were included at the Maastricht University Medical Centre+ (MUMC+). The study was approved by the Institutional Review Board of the MUMC+.

All patients were aged over 18 years. The patients either had electrocardiographic documentation of AF at presentation or were patients with pre-hospital conversion if they had previous electrocardiographically documented AF with a verified symptom-rhythm correlation or if the current episode was electrocardiographically documented by the general practitioner and patients converted on their way to the hospital. For the purpose of this study the following exclusion criteria were applied: a history of persistent or permanent AF, haemodynamic instability, or signs of acute coronary syndrome or heart failure at initial work-up. Patients were treated at the discretion of the treating physician; no additional study-related action was taken. The institutional protocol allowed for both forms of cardioversion, depending on patients’ profiles, timing of eventual cardioversion in relation to last meal, and physicians’ preferences and experiences.

Baseline characteristics were collected, including age, sex, duration of AF, current symptoms, medical history, and (prior) echocardiographic data. Patients underwent a full physical examination, a 12-lead electrocardiogram analysed with software from the MUSE system (GE Medical Systems, Milwaukee, WI, USA), and laboratory investigation at the ED. Information regarding therapeutic strategy including rate versus rhythm control was noted. We compared characteristics between patients with SCV and non-spontaneous conversion (non-SCV).

For the purpose of this study patients with a history of persistent or permanent AF, defined as a previous episode of AF lasting longer than >48 h, were excluded. The duration of the current episode was not an exclusion criterion; therefore episodes longer than 48 h were also included if the patient had no history of persistent or permanent AF. Conversion was defined as spontaneous if the patient converted to SR without active cardioversion, either ECV or PCV, before presentation at the ED or within 3 h after ED presentation, which was the time interval allowing proper work-up towards active cardioversion and during which spontaneous cardioversion could happen.

Data management and analysis were performed using IBM SPSS version 25 (Armonk, NY, USA). Results were reported as mean ± standard deviation or median with interquartile range (IQR). A chi-square or Fisher’s exact test was used to compare categorical variables. Normally distributed continuous covariates were compared using the Student’s t-test. For comparison of skewed continuous covariates the Mann-Whitney U test was used. A binary logistic regression was performed, using backward selection until all variables in the model reached a p-value <0.05, to identify possible determinants for SCV. All variables showing a significant (p < 0.05) univariable relationship for SCV were included in the regression analysis. A p-value of <0.05 was considered statistically significant.

Spontaneous conversion to SR occurred in 158 (16.8%) patients. In patients without SCV, an active cardioversion was attempted in 487 (51.6%), rate control was chosen in 31.4%, and 2 patients received a pacemaker (0.2%) because of sick sinus syndrome. Pharmacological cardioversion was performed in 276 of 487 (56.7%) patients; flecainide was the preferred drug in the majority of cases (93.1%). Electrical cardioversion was performed in 211 of 487 (43.3%) patients. Pharmacological cardioversion was successful in 80.1% of cases, ECV in 92.9%; the overall success rate of cardioversion was 85.8%. An overview of the treatment strategy is presented in Fig. 2.

The median duration from onset of symptoms until the end of the observation period was 4.0 h (IQR 7, range 0–86 h) in patients with SCV, and 11.0 h (IQR 19, range 3–1355 h) in patients without SCV. The median observation time at the ED pending SCV was 32 min (IQR 81, range 0–165 min). The number of patients in SR after 1 h was 100 (10.6%), and after 2 h 138 (14.6%). The mean age of the SCV and non-SCV groups was comparable (70 ± 11 vs 69 ± 13 years, p = 0.257, respectively). There was a trend towards more spontaneous cardioversions in female patients (53.8 vs 46.0%, p = 0.073). Patients with SCV less frequently had a history of hypercholesterolaemia (25.9 vs 36.3%, p = 0.013), coronary artery bypass grafting (1.9 vs 7.5%, p = 0.009), chronic obstructive pulmonary disease (0.6 vs 3.8%, p = 0.040), and less frequently had a history of valve surgery (1.3 vs 5.6%, p = 0.021). Mean body mass index (BMI) was lower in patients with SCV (27.0 vs 28.5 kg/m², p = 0.001). First-detected AF was more common in patients with SCV than in non-SCV patients (41.8 vs 32.0%, p = 0.017, respectively). In addition, patients with SCV had a shorter median duration of symptoms (3.0 h; IQR 5 vs 8.0; IQR 19, p < 0.001) and more often suffered symptoms of near-collapse (11.4 vs 6.1%, p = 0.018), palpitations (81.6 vs 72.0%, p = 0.012), chest pain (27.8 vs 18.6%, p = 0.008), and dizziness (20.3 vs 14.9%, p = 0.093). Patients complaining of near-collapse more often had first-detected AF (58% vs 42%, p < 0.001). Patients with SCV more often had a higher ventricular rate (125 vs 118 bpm, p = 0.004), longer QTc time during AF (460 ms ± 34 vs 452 ms ± 34, p = 0.035) and more often had a lower left atrial volume index (LAVI) (<42 ml/m²) (61.3 vs 47.8%, p = 0.004). A longer QTc was observed in patients who had a breakthrough arrhythmia (460 ± 40 ms in patients with antiarrhythmic drugs (AAD) vs 450 ± 40 ms in patients without AAD, p < 0.001).

Logistic regression analysis showed that duration of AF <24 h (OR 7.7, 95% CI 3.5–17.2, p < 0.001), LAVI <42 ml/m² (OR 1.8, 95% CI 1.2–2.8, p = 0.010), symptoms of near-collapse at presentation (OR 2.4, 95% CI 1.2–5.1, p = 0.018), a lower BMI (OR 0.9, 95% CI 0.91–0.99, p = 0.028), a longer QTc time during AF (OR 1.01, 95% CI 1.0–1.02, p = 0.002) and first-detected AF (OR 2.5, 95% CI 1.6–3.9, p < 0.001) were independent determinants of early SCV (Tab. 2).

In patients with a duration of AF <24 h, first-detected AF, and smaller LAVI, the SCV rate was high: 38% (38 of 99 patients).

The substantial rates of SCV of acute AF in this and other reports [1, 5‐8, 10], combined with the rising prevalence of AF, cost aspects and the possible complications associated with acute cardioversion may justify less aggressive arrhythmia management. A wait-and-see strategy for patients with stable AF with onset of symptoms <48 h encompasses standard rate control measures, adequate initiation of anticoagulation and delayed cardioversion within 48 h if necessary. In a small study investigating this wait-and-see approach, two-thirds of 35 patients had converted spontaneously within 48 h [5]. This finding was recently confirmed by the RACE 7 ACWAS trial, a multicentre randomised controlled trial which compared a wait-and-see approach (symptom alleviation and delayed cardioversion when necessary) with immediate cardioversion in patients with recent-onset AF [9, 19]. This study showed that a wait-and-see approach is non-inferior with respect to the presence of SR at 4 weeks when compared to immediate cardioversion; almost 70% of the patients in the wait-and-see group had SCV to SR within 48 h. Those results support the opinion that a wait-and-see approach is a worthy alternative to discuss with patients but will not replace early cardioversion completely. Early cardioversion could be beneficial, since it shortens the time until conversion, which might eliminate symptoms earlier. However, in the above-mentioned study symptom control was similar in both groups [9]. Another advantage of early pharmacological conversion is the observation of the antiarrhythmic response, which tests the safety of a pill-in-the-pocket approach [20]. Therefore, patients with stable recent-onset AF and their physicians might choose between the two approaches in a shared decision-making process.

The results of the current study facilitate the identification of patients with a high likelihood of SCV to SR and the implementation of a wait-and-see approach. Identification of acute AF patients susceptible to spontaneous restoration of SR may reduce the number of emergency visits (especially in stable patients with recurrent episodes and a known symptom-rhythm correlation), costs and unnecessary and potentially harmful treatment.

Since this study was not designed to evaluate SCV rates, our results are probably an underestimation of the true SCV rate: patients who received active cardioversion might have converted spontaneously if a wait-and-see approach had been adopted. Due to the observational study design we could not adjust for this possible bias. Patients with pre-hospital SCV were included in the analysis. Even if the likelihood of those patients having AF was extremely high, one cannot be completely certain that those patients had an actual episode of AF, which could have led to an overestimation of the SCV rate.