Atrial Fibrillation Risk Assessment after Embolic Stroke of Undetermined Source.

Khouloud Poli, Lars Kellert, Stefan Kääb, Steffen Massberg, Marianne Dieterich, Wolf-Rüdiger Schäbitz, Alkisti Kitsiou, Jörg Berrouschot, Ulf Ziemann, Christine S Zuern, Aenne S von Falkenhausen, Sven Poli, Sebastian Clauss, Elodie Eiffener, Johannes Wischmann, Johanna Müller, Sonja Schönecker, Moritz F Sinner, Katharina Feil

Journal: Annals of neurology 2023;93(3):479-488

PMID: 36373166

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Abstract

OBJECTIVE

Approximately 20% of strokes are embolic strokes of undetermined source (ESUS). Undetected atrial fibrillation (AF) remains an important cause. Yet, oral anticoagulation in unselected ESUS patients failed in secondary stroke prevention. Guidance on effective AF detection is lacking. Here, we introduce a novel, non-invasive AF risk assessment after ESUS.

METHODS

Catch-Up ESUS is an investigator-initiated, observational cohort study conducted between 2018 and 2019 at the Munich University Hospital. Besides clinical characteristics, patients received ≥72 h digital electrocardiogram recordings to generate the rhythm irregularity burden. Uni- and multivariable regression models predicted the primary endpoint of incident AF, ascertained by standardized follow-up including implantable cardiac monitors. Predictors included the novel rhythm irregularity burden constructed from digital electrocardiogram recordings. We independently validated our model in ESUS patients from the University Hospital Tübingen, Germany.

RESULTS

A total of 297 ESUS patients were followed for 15.6 ± 7.6 months. Incident AF (46 patients, 15.4%) occurred after a median of 105 days (25th to 75th percentile 31-33 days). Secondary outcomes were recurrent stroke in 7.7% and death in 6.1%. Multivariable-adjusted analyses identified the rhythm irregularity burden as the strongest AF-predictor (hazard ratio 3.12, 95% confidence interval 1.62-5.80, p < 0001) while accounting for the known risk factors age, CHA DS -VASc-Score, and NT-proBNP. Independent validation confirmed the rhythm irregularity burden as the most significant AF-predictor (hazard ratio 2.20, 95% confidence interval 1.45-3.33, p < 0001).

INTERPRETATION

The novel, non-invasive, electrocardiogram-based rhythm irregularity burden may help adjudicating AF risk after ESUS, and subsequently guide AF-detection after ESUS. Clinical trials need to clarify if high-AF risk patients benefit from tailored secondary stroke prevention. ANN NEUROL 2023;93:479-488.

Address: Department of Cardiology, University Hospital, Ludwig Maximilians University of Munich, Munich, Germany.; German Center for Cardiovascular Research (DZHK), partner site: Munich Heart Alliance, Munich, Germany.; Department of Neurology, University Hospital, Ludwig Maximilians University of Munich, Munich, Germany.; Department of Neurology and Stroke, University Hospital, Eberhard-Karls University Tübingen, Germany.; Institute of Surgical Research at the Walter-Brendel-Center of Experimental Medicine, University Hospital, Ludwig Maximilians University of Munich, Munich, Germany.; Hertie Institute for Clinical Brain Research, Eberhard-Karls University, Tübingen, Germany.; Department of Cardiology, Eberhard-Karls University, Tübingen, Germany.; Cardiology Division, Department of Medicine, University Hospital, and Cardiovascular Research Institute, Basel, Switzerland.; Department of Neurology, Klinikum Altenburger Land, Altenburg, Germany.; Department of Neurology, University Hospital, Evangelisches Klinikum Bethel, University of Bielefeld, Bielefeld, Germany.; German Center for Vertigo and Balance Disorders, Ludwig Maximilians University of Munich, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

DOI: 10.1002/ana.26545

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MeSH Terms: Humans, Atrial Fibrillation, Embolic Stroke, Risk Assessment, Risk Factors, Stroke, Intracranial Embolism