Unrecognized PAF and the consequent lack of prophylactic anticoagulant treatment may result in significant morbidity first presenting as a heart failure, stroke, systemic embolism, and occasionally death. It is generally accepted that intermittent ECG monitoring (Holter ECG) has low sensitivity to identify patients with PAF. The commonly used 24-h Holter ECG monitoring has been found to reach PAF diagnostic sensitivity of 2.4–9.4 % [
19‐
21]. Longer continuous non-stop ECG monitoring has been shown to increase PAF detection. In a sub-study of TRENDS, a single 24-h Holter ECG diagnosed PAF in 3 %, whereas 7, 21, or 30 days of monitoring diagnosed PAF in 6, 9, or 11 %, respectively [
22]. The EMBRACE study (The 30-Day Cardiac Event Monitor Belt for Recording Atrial Fibrillation After a Cerebral Ischemic Event) used noninvasive ambulatory ECG monitoring in patients with cryptogenic stroke or TIA for 30 days. Detection of atrial fibrillation improved fivefold and indication of anticoagulant treatment nearly doubled when compared with standard practice of short-duration ECG monitoring. AF was detected in 16.1 % of patients in the intervention group, compared with 3.2 % in the control group [
23]. ICM devices for long-term ECG monitoring have been used primarily for differential diagnosis of syncope [
24]. Cotter et al. reported “Reveal XT” PAF identification in 25.5 % (13 patients) of 51 patients with unexplained stroke [
14]. Sensitivity and specificity of “Reveal XT” device for PAF was detected to be 96.1 and 85.4 % respectively (3-year non-stop monitoring) [
25]. A large randomized clinical trial The Cryptogenic Stroke and Underlying Atrial Fibrillation trial (CRYSTAL AF) compared long-term ECG monitoring by ICM with conventional ECG Holter monitoring in patients with recent CS. After 12 months ICM monitoring detected over 7 times more patients with PAF than ECG Holter monitoring. Three-year follow-up detected 30 % PAF occurrence in the ICM group compared to 3 % in the Holter group [
26]. Choe evaluated sensitivity and negative predictive value (NPV) of various external monitoring techniques in a cryptogenic stroke cohort. Simulated intermittent monitoring strategies were compared with continuous rhythm monitoring in 168 ICM patients of the CRYSTAL AF trial. Short-term monitoring included a single 24-h, 48-h and 7-day Holter, and 21-day and 30-day event recorders. Periodic monitoring consisted of monthly monitoring by 24-h Holters and quarterly monitoring by 24-h, 48-h and 7-day Holters. For a single monitoring period, sensitivity for AF diagnosis was lowest with 24-h Holters (1.3 %) and highest with 30-day event recorders (22.8 %). NPV ranged from 82.3 to 85.6 % for all single external monitoring strategies. Quarterly monitoring with 24-h Holters had 3.1 % sensitivity, whereas quarterly 7-day monitors increased it to 20.8 %. NPV of various types of repetitive periodic monitoring were similar at 82.6 to 85.3 %. Long-term continuous monitoring was superior in detecting AF compared to all types of intermittent monitoring evaluated (p <0.001) [
27]. Ritter et al. presented 17.0 % PAF detection in ICM group in comparison with 1.7 % in 7-day ECG Holter group (p = 0.0077) [
28].
Finding a new algorithm for detecting PAF in standard clinical practice should be of great interest as it would allow early indication of anticoagulant therapy in stroke/TIA patients. Additional information that would help to characterize stroke subtype could be provided by genetic data. Study of gene polymorphisms associated with an increased risk of AF suggests that subtle alterations in developmental factors, cell signalling, extracellular matrix regulation, and ion channels function are involved in arrhythmia pathogenesis. Large genome-wide association studies (GWAS) have found that the genetic markers close to the PITX2 gene on chromosome 4q25 and to the ZFHX3 gene on 16q22 are associated with both AF and cardio-embolic stroke [
17,
18]. The PITX2 gene plays a critical role in development of left atrium and pulmonary vein myocardium. This particular region has been implicated to initiate and maintain AF. The expression patterns of the ZFHX3 gene in human cardiac and pulmonary tissue are not clear, nor are the mechanisms by which variants in this gene may predispose to AF.