Atrial fibrillation (AF) is the most common type of arrhythmia. It affects millions of people worldwide, and its prevalence increases with age.1 AF is associated with stroke and other thromboembolic events, low exercise capacity, impaired quality of life, heart failure, left ventricular dysfunction, and increased mortality.2 In addition to aging, various clinical conditions are associated with AF, including hypertension, diabetes, coronary artery disease, valvular heart disease, cardiomyopathies, symptomatic heart failure, atrial septal and other congenital heart defects, obesity, thyroid dysfunction, chronic obstructive pulmonary disease, sleep apnea, and chronic kidney disease. Screening for predictors of AF in at-risk groups plays a key role in preventing the condition.2

Previous studies have established the clinical value of left atrial size and premature atrial contraction, based on Holter recordings and echocardiography, as predictors of AF.3,4 Additionally, maximum P-wave duration (Pmax) and P-wave dispersion (PWD) have been used to assess the risk of AF.5–8 PWD is defined as the difference between Pmax and minimum P-wave duration (Pmin) recorded by 12-lead surface electrocardiography (ECG).6 Measurement of PWD is an easy-to-use, low-cost method that reflects atrial muscle activation, left atrial size, and changes in electrical conduction in the atrium.7

Cardiac troponin I is a specific and sensitive marker of cardiac muscle damage. Recent studies have shown that elevated levels of high-sensitivity cardiac troponin T (hs-TnT) are associated with poor cardiovascular outcomes in patients with AF.9–11 Furthermore, a recent study found that elevated hs-TnT was associated with AF recurrence in patients with AF independently of traditional risk factors and left atrial size.12

Although PWD and cardiac troponin have been reported to independently predict AF recurrence, to our knowledge no study has assessed the usefulness of combined PWD and cardiac troponin I values for predicting recurrent AF in patients with paroxysmal AF (PAF). We therefore investigated the clinical value of the combined use of PWD and cardiac troponin I values for predicting AF recurrence in patients presenting to the emergency department with PAF.

This cross-sectional case-control study included 110 patients who presented to the emergency department with palpitations within the preceding 48 hours between April 2017 and December 2018. Patients presenting with sinus tachycardia (n=10), supraventricular tachycardia (n=7), ventricular tachycardia (n=3), ventricular extrasystoles (n=8), multifocal atrial tachycardia (n=5), coronary artery disease (n=5), and other conditions (n=7) were excluded; thus, 65 patients with PAF were finally included. The study was approved by the local ethics committee, and all participants provided informed consent. All patients underwent routine 12-lead ECG and blood tests on admission to the emergency department. Patients with no history of chronic AF were diagnosed with PAF based on ECG findings. All patients were examined by a cardiologist in the emergency department and appropriate medical interventions and follow-up procedures were performed. Normal sinus rhythm was restored in all patients through medical management without the need for electrical therapy.

Cardiac troponin I concentrations and routine blood parameters were measured in blood samples collected at admission. PWD, defined as the difference between the longest and shortest P-waves on 12-lead ECG, was recorded. Two independent clinicians measured PWD, and the inter- and intraobserver agreement rates were 98.5% and 99%, respectively. All patients were closely monitored for six months for recurrent AF. Patients with recurrent arrhythmias were re-examined in the emergency department and underwent 12-lead surface ECG to assess cardiac rhythm. Blood samples were taken to measure troponin I levels. The presence of AF on ECG was taken to indicate recurrent PAF.

Patients were divided into three groups according to baseline troponin I and PWD values (group 1, troponin I 0.11 ng/dl and PWD 44.5 ms; group II, troponin I 0.11 ng/dl and PWD≥44.5 ms, or troponin I≥0.11 ng/dl and PWD 44.5 ms; group III, troponin I≥0.11 ng/dl and PWD≥44.5 ms).

The study included 65 patients with PAF. Patients were classified as having recurrent or non-recurrent AF. AF recurred in 21 (32.3%) patients within six months. Selected descriptive and clinical characteristics of the groups are shown in Table 1 according to AF recurrence status. Clinical characteristics and laboratory findings were not significantly different between the recurrent and non-recurrent AF groups (Table 2).

P-wave dispersion and baseline troponin I values are shown in Table 3. PWD (p=0.001) and baseline troponin I levels (p=0.004) were significantly higher in patients with AF recurrence than in those without recurrence. Furthermore, the percentage of troponin I-positive patients in the recurrent AF group was significantly higher than in the non-recurrent group.

Receiver operating characteristic curve analysis curve analysis was performed to determine the optimal troponin I and PWD cut-off values for predicting AF recurrence. Troponin I≥0.11 ng/ml predicted AF recurrence with a specificity of 61.9% and sensitivity of 72.7% (Figure 1). PWD≥44.5 ms predicted AF recurrence with a specificity of 79.5% and sensitivity of 71.4% (Figure 2).

Figure 1.

Receiver operating characteristic curve of troponin level and atrial fibrillation recurrence. AUC: area under the curve.

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Figure 2.

Receiver operating characteristic curve of P-wave dispersion and atrial fibrillation recurrence. AUC: area under the curve.

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In total, 22 (%) patients were included in group III (troponin I≥0.11 ng/ml and PWD≥44.5 ms, 13 (20%) were included in group II (troponin I≥0.11 ng/ml or PWD≥44.5 ms), and 30 (46.2%) were included in group I (troponin I 0.11 ng/ml and PWD 44.5 ms). The rate of AF recurrence was significantly higher in group III than in group I (59.1% vs. 16.7%, p=0.001) and group II (59.1% vs. 23.1%, p=0.039) (Figure 3).

Figure 3.

Comparison of atrial fibrillation recurrence rates in the three groups.

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Multivariate logistic regression analysis revealed that the troponin I and PWD values in group II (odds ratio [OR]: 1.025, 95% confidence interval (CI): 0.189-5.553, p=0.977) and group III (OR:7.236, 95% CI: 1.879-27.861, p=0.004) were independent predictors of AF recurrence (Table 4).

We investigated the clinical value of the combined use of troponin I levels and PWD for predicting AF recurrence in patients with PAF. We found that the combined use of troponin I and PWD was superior for predicting AF recurrence than either measure alone. To our knowledge, our study is the first to demonstrate the clinical importance of the combined use of troponin I and PWD for predicting AF recurrence in patients with PAF.

Because AF is associated with thromboembolic events and various cardiac and systemic conditions that affect quality of life, treatment and prevention of complications are essential. Thus, predicting the recurrence of AF in patients with PAF is important. Several parameters that can be obtained non-invasively have been used to predict AF, including left atrial size, Holter recordings, and premature atrial contractions,3–5 as well as ECG and laboratory parameters.

Prolonged intra- and interatrial conduction times and non-homogeneous propagation of sinus impulses are characteristic of PAF. An increase in PWD indicates heterogeneous intra- and interatrial conduction.13 Previous studies have shown that PWD is significantly greater in patients with PAF than in controls, and that PWD≥40 ms can differentiate patients with PAF with 83% sensitivity and 85% specificity.7,9,13–16 Moreover, atrial diameter has a significant effect on P-wave duration and PWD, while reverse atrial electrical remodeling has been shown to reduce both parameters.14,17 Our finding that PWD was significantly greater in the recurrent AF than in the non-recurrent AF group is consistent with previous studies. Taken together, our findings suggest that PWD is an independent predictor of AF recurrence.

Cardiac troponin I is a sensitive and specific marker of cardiac muscle damage. Several studies have shown that increased serum cardiac troponin T levels are associated with poor cardiovascular outcomes and AF recurrence in patients with AF.10–12,18 Our finding that troponin I levels were markedly higher in patients with than without AF recurrence is consistent with previous findings. Furthermore, we classified troponin I values as positive or negative based on our laboratory reference range and found that troponin I positivity was markedly higher in the recurrent AF than in the non-recurrent AF group. These findings suggest that elevated cardiac troponin I levels and positivity are independent predictors of AF recurrence.

Previous studies found that the combination of two parameters has higher predictive value that either parameter alone.19–21 Although PWD and troponin I levels are independently associated with increased risk of AF recurrence, the clinical importance of the combined use of these values to predict AF recurrence in patients with PAF has not been investigated. We found that the rate of AF recurrence was significantly higher in patients in group III than in those in groups I and II. Moreover, multivariate regression analysis revealed that the patients in group III had a roughly 2.5-fold higher rate of AF recurrence than those in group II, and that the OR of group III (7.236) was higher than that of group II (1.025). Our findings suggest that the combined use of PWD and baseline troponin I values has higher predictive value than PWD or troponin alone.

Our study had some limitations. First, the sample size was small. Second, we measured only baseline troponin I values and did not perform serial troponin I measurements. Third, only patients with PAF were included in the study. Comparison of PAF and persistent AF patients with healthy individuals could have provided greater insight. Further prospective studies with larger samples are needed to better understand the clinical value of the combined use of PWD and troponin I levels.

PWD is a simple and easily measured ECG marker, and troponin I can be obtained quickly and inexpensively during routine laboratory analysis. In this study, we show for the first time that the combined use of PWD and basal troponin I levels is a better predictor of AF recurrence than either value alone.

The authors have no conflicts of interest to declare.