Authors

• Lucija Lisica — Klinički bolnički centar Split, Split, Hrvatska — ORCID: 0000-0003-1904-0259
• Zrinka Jurišić — Klinički bolnički centar Split, Split, Hrvatska — ORCID: 0000-0001-7583-9036

Abstract

Atrial fibrillation (AF) is one of the preventable risk factors for embolic ischemic stroke. The high prevalence and the possibility of stroke prevention suggest the need for effective screening for AF. The aim of this study was to assess the prevalence of and methods for diagnosing AF in patients with ischemic stroke, compare their clinical characteristics, and subsequently outcomes in the AF and non-AF group. This was a retrospective observational study. Medical history of patients with ischemic stroke in 2019 was collected and analyzed. Out of the total number of the patients with ischemic stroke, 39% had AF, which was newly discovered in 50.3% of all patients with AF. Almost three-quarters (73%) of patients with known AF in their medical history were not receiving adequate anticoagulation therapy. Most of the patients with newly discovered AF (87%) were diagnosed using a standard 12-lead ECG, while the rest was diagnosed using 24-hour Holter monitoring (12.5%). AF was associated with mortality as well as with a higher CHA 2 DS 2 -VASc score. As many as half of patients with AF in our cohort were diagnosed with AF only after suffering a stroke. In addition, most of the previously diagnosed patients with AF were not receiving adequate anticoagulation therapy. Outcomes were worse in patients with stroke who had concomitant AF, especially those with higher CHA 2 DS 2 -VASc scores. Therefore, more frequent screening of patients is encouraged, with continuous monitoring as an ideal solution.

Keywords

atrial fibrillation, ischemic stroke, electrocardiography

DOI

Full Text

## Introduction Atrial fibrillation (AF) is the most common arrhythmia in clinical practice and is associated with increased morbidity and mortality in the globally aging population (1). The prevalence of AF is increasing, primarily due to better diagnostic methods and longer life expectancy (2). AF is usually classified as clinical or subclinical. The diagnosis of clinical AF, which may be symptomatic or asymptomatic, is established by either a standard 12-lead ECG or a single-lead ECG detecting an episode of AF longer than 30 seconds (3). Subclinical AF refers to asymptomatic individuals with observed episodes of fast atrial rhythm with a frequency greater than >175 beats per minute in an intracardiac electrograms, which have been confirmed as episodes of AF, atrial undulation, or atrial tachycardia (4-6). AF is one of the preventable risk factors for embolic ischemic stroke (7). The growing prevalence, the high proportion of asymptomatic fibrillation, and the possibility of stroke prevention suggest the need to introduce effective screening for this arrhythmia (8, 9). The current recommendation of the European Society of Cardiology (ESC) is to employ opportunistic screening of the population over the age of 65 by palpating the pulse or recording a 12-lead ECG (4). The most significant issue related to screening, apart from the need for continuous monitoring, is the difficulty of diagnosing AF due to its often paroxysmal nature, which is why we may miss some AF episodes when monitoring in-hospital patients immediately after a stroke (10, 11). Frequently used 24-hour Holter monitoring, in a series of studies on the detection of AF after stroke or transient ischemic attack, showed an AF detection rate between 1.2% and 45%. Despite the high detection rates in some studies, most studies showed a detection rate between 2% and 9%. For comparison, 6.3% of serial 12-lead ECGs recordings in patients with stroke in the first 72 hours after admission detected AF, in a study by Douen et al. Similarly, in a study by Kamel et al., 6.9% of serial 12-lead ECGs in the first 90 days after ischemic stroke detected AF (12-14). This study aimed to examine the clinical aspects of patients hospitalized for ischemic stroke, especially those with AF, and to determine the frequency and method of detection of AF in these patients. We examined the demographic characteristics of patients, the frequency and adequacy of oral anticoagulant therapy in patients with AF, the comorbidities, and their impact on the frequency of AF. ## Patients and Methods This was a retrospective observational study conducted at the University Hospital Center Split, Department of Neurology. Data on all patients with the leading diagnosis of ischemic stroke (MKB-10 diagnosis I63.0-I63.9) in 2019 were collected from the protocol and medical history. Data for each subject included: age, sex, AF history, history of anticoagulant and antiplatelet therapy, MSCT brain scan and history on pre-existing ischemic stroke, 12-lead ECG, 24-hour Holter monitoring results, and comorbidities (hypertension, diabetes, heart failure (HF), and cardiovascular disease). AF was diagnosed from previous medical records, a 12-lead ECG or Holter monitoring record, and records from implantable cardiac devices. HF was defined according to the current ESC Guidelines, while cardiovascular diseases were defined using the CHA2DS2-VASc score definition (4, 15). Age groups of patients were also determined by the CHA2DS2-VASc score groups (≤65, 65-74, ≥75) (4). The CHA2DS2-VASc score was calculated for all patients. The study was approved by the Ethics Committee of the University Hospital Center Split. All data were analyzed in SPSS 20. Continuous variables were presented as a median and interquartile range, while categorical variables were presented as absolute numbers and percentages. Assessment of the normality of the distribution was performed using the Kolmogorov-Smirnov test. For data processing, we used the χ2 test, the Mann-Whitney test, and logistic regression. The results were interpreted at a significance level of p 2DS2-VASc score) as well as the relationship between the incidence of recurrent ischemic stroke and the incidence of AF. ### TABLE 1: Correlation of atrial fibrillation with components of the CHA 2 DS 2 -VASc score. | **Atrial fibrillation** | **Atrial fibrillation** | **Atrial fibrillation** | **Atrial fibrillation** | **Atrial fibrillation** | **Atrial fibrillation** | **Atrial fibrillation** | | --- | --- | --- | --- | --- | --- | --- | | | **Total (n=879)** **n (%)** | **No** **(n=533)** **n (%)** | **Yes** **(n=346)** **n (%)** | ***P*a** | **OR (95% CI)** | ***P*b** | | **Heart failure** | **220 (25)** | **95 (18)** | **125 (36)** | **a χ2 b binary logistic regression The probability of developing AF in the group of subjects with HF was higher than in the group of subjects without HF. In this study, the probability of having AF was twice as high in women than in men. There was also a statistically significant association between age groups and AF (**Table 1**). The median CHA2DS2-VASc score in the AF group was higher than in the group without AF (z = 9.1) **(****Table 2****)**. ### TABLE 2: Value of the CHA 2 DS 2 -VASc score in correlation with atrial fibrillation. | | | **CHA2DS2-VASc score** **MED (Q1-Q3; min-max)** | ***Pa*** | | --- | --- | --- | --- | | **Atrial fibrillation** | **No** | 5 (4-6; 2-9) | aMann-Whitney test The probability of a fatal outcome was higher in the group of subjects with AF than in the group of subjects without it. The probability of a fatal outcome increased with each increase in the CHA2DS2-VASc score by 1 **(****Table 3****)**. ### TABLE 3: Correlation of AF and CHA 2 DS 2 -VASc score with fatal outcomes in the whole cohort. | | | **Fatal outcome** | **Fatal outcome** | | | | | --- | --- | --- | --- | --- | --- | --- | | | | **No (n=755)** | **Yes (n=124)** | **P** | **OR (95% CI)** | **Pc** | | Atrial fibrillation | n (%) | 261 (35) | 85 (68) | a | 4.1 (2.7-6.2) | 2DS2-VASc score | MED (Q1-Q3; min-max) | 5 (4-6; 2-9) | 6 (5-7; 2-8) | b | 1.7 (1.4-2) | a χ2 test bMann Whitney clogistic regression Furthermore, we conducted multivariate logistic regression for mortality in which mortality was the dependent variable, while the CHA2DS2-VASc score and AF were independent variables. We confirmed the association of both AF and CHA2DS2-VASc score with fatal outcome (**Table 3**). After conducting logistic regression, the probability of a fatal outcome was 3.1 times higher in the group of subjects with AF (95% CI = 2-4.7; p 2DS2-VASc to be a cumulative factor of thromboembolic risk in all patients, including those in sinus rhythm. In a study by Rende et al., the cumulative incidence of ischemic stroke in patients without AF with a CHA2DS2-VASc score ≥4 was similar to the incidence of ischemic stroke in patients with AF and a CHA2DS2-VASc score of 2. A CHA2DS2-VASc score ≥2 was also shown to be a predictor of fatal outcome and AF incidence (26). In this study, patients with AF, as well as with a fatal outcome, had a higher median CHA2DS2-VASc score than the group without AF. These results are important because the literature mentions the possibility of introducing anticoagulant therapy after ischemic stroke in patients who have a high CHA2DS2-VASc score even though they have not been diagnosed with AF. Components of thromboembolic risk are also risk factors for AF itself, and these results suggest the need for more frequent screening of AF in patients with a higher CHA2DS2-VASc score (27). Of the 400 24-hour Holter monitoring examinations performed in patients with stroke at this center, 5.5% of them detected unknown AF that was not observed on 12-lead ECG at admission. It should be noted that 4.75% of 24-hour Holter monitoring examinations showed sinus rhythm, and AF was detected only by a 12-lead ECG. A quarter of 24-hour Holter monitoring examinations were performed in patients who already had AF in a 12-lead ECG, which is sufficient for diagnosis according to ESC guidelines (4). A recent study by Huang et al. focused on this issue, comparing the effectiveness of detecting AF in patients admitted for ischemic stroke with a 24-hour Holter monitoring and serial recording of a 12-lead ECG for five consecutive days. No statistically significant difference was found between these two methods. This approach is more pragmatic and could be considered the first-choice method for the diagnosis of paroxysmal AF among elderly patients with ischemic stroke (28). This study has several limitations. Firstly, data were collected retrospectively. Data and clinically documented previous ischemic strokes do not detail their characteristics, so analysis of stroke subtypes was not possible. Silent lacunar ischemic strokes, which are very common in the elderly population, have also been reported as a previous ischemic incident, although more commonly associated with microangiopathy (20). History on the regular use of anticoagulant therapy was not completely reliable, so there is a possibility that the compliance of subjects in this study was even lower. This study has shown that CHA2DS2-VASc score and AF are independent risk factors for death. A high CHA2DS2-VASc score is not predictive of poor outcomes only in patients with AF, but also in patients in sinus rhythm. Therefore, future research should focus on the potential benefits of anticoagulant therapy in this group of patients. The CHA2DS2-VASc score was higher in patients with AF, suggesting the need for more careful monitoring of patients with ischemic stroke and high CHA2DS2-VASc scores, who are more likely to have occult AF (29). ## Acknowledgments We want to thank dipl. eng. Vesna Čapkun for help with statistical analysis. This article is based on the master’s thesis: Lisica L. Učestalost i način dokazivanja atrijske fibrilacije u bolesnika hospitaliziranih zbog ishemijskog moždanog udara (diplomski rad). Split: Medicinski fakultet; 2021.29

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