Atrial Fibrillation After Ischemic Stroke Detected by Chest Strap-Style 7-Day Holter Monitoring and the Risk Predictors: EDUCATE-ESUS.

AIM: This study aimed to investigate the diagnostic yield of 7-day Holter monitoring for detecting covert atrial fibrillation (AF) in patients with recent embolic stroke of undetermined source (ESUS) and to identify the pre-entry screening biomarkers that had significant associations with later detection of AF (clinicaltrials.gov. NCT02801708). METHODS: A total of 206 patients who have recent ESUS without previously documented AF underwent Holter electrocardiography using a chest strap-style monitor. External validation of biomarkers predictive of AF was performed using 83 patients with ESUS who were implanted with insertable cardiac monitors. RESULTS: The 7-day Holter monitoring started at a median of 13 days after the onset of stroke. AF was detected in 14 patients, and three of these showed a single AF episode lasting ＜2 min. The median time delay to the first documented AF was 50 h. Each of serum brain natriuretic peptide ≥ 66.0 pg/mL (adjusted odds ratio 5.23), atrial premature contractions (APCs) ≥ 345 beats (3.80), and APC short runs ≥ 13 (5.74) on 24-h Holter prior to the 7-day Holter showed a significant association with detection of AF, independent of age and physiological findings in this derivation cohort, and all of these showed a significant association in the validation cohort (adjusted odds ratio 6.59, 7.87, and 6.16, respectively). CONCLUSIONS: In recent ESUS patients, the detection rate of AF using the 7-day Holter monitoring was 6.8% (95% CI 4.1%-11.1%). Brain natriuretic peptide, APC count, and APC short runs in the standard clinical workup seemed to be predictors of covert AF.

[Measurement of Prothrombin Fragment 1+2 for the Assessment of Anticoagulant Activity in Patients Treated with Warfarin or Non-vitamin K Antagonist Oral Anticoagulant].

[Background and purpose] Prothrombin fragment 1+2 (PF1+2) is a sensitive marker for blood coagulation system. In order to evaluate anticoagulant activity in patients treated with warfarin or non-vitamin K antagonist oral anticoagulant (NOAC), we measured plasma levels of PF1+2 and evaluated anticoagulant activity by each anticoagulant agent. [Methods] Subjects were 28 patients, 17 men and 11 women, 77±6 year old, with oral anticoagulant therapy for secondary prevention of stroke. We measured plasma levels of PF1+2 in 70 times in 7 patients treated with warfarin, and 154 times in 27 patients treated with NOAC. PT-INR was simultaneously measured in patients treated with warfarin. [Results] In warfarin treatment groups, PT-INR values were median 1.96 (IQR 1.8-2.1) and PF1+2 levels were median 111 pmol/l (IQR 95-141). All PF1+2 levels were below the upper limit of normal range, but 12 values (17%) of them in 5 patients were below the lower limit of normal range. 8 of the 12 values were at PT-INR below 2.5, and 1 of whom developed intracerebral hemorrhage. Plasma levels of PF1+2 in patients treated with dabigatran 150mg BID, dabigatran 110mg BID, rivaroxaban 15mg QD, rivaroxaban 10mg QD, apixaban 5mg BID, apixaban 2.5mg BID, and edxaban 30mg QD were median 116 pmol/l (IQR 99-136), 132 pmol/l (IQR 99-162), 109 pmol/l (IQR 100-125), 133 pmol/l (IQR 100-177), 88 pmol/l (IQR 76-102), 148 pmol/l (IQR 93-167), 221 pmol/l (IQR 208-234). They were all above the lower limit of the normal range, 3 of which were above the upper limit of the normal range. Excessive suppression of thrombin production was more frequently seen in warfarin treatment than in NOAC treatment (p<0.05). [Conclusion] In warfarin treatment, thrombin production was suppressed excessively in 17%, although it was not in NOAC treatment. (Received September 21, 2016; Accepted December 26, 2016; Published May 1, 2017).