Kevin O’Connor, MD
Bhat A, Mahajan V, Chen HHL, Gan GCH, Pontes-Neto OM, Tan TC. Embolic Stroke of Undetermined Source: Approaches in Risk Stratification for Cardioembolism. Stroke. 2021;52:e820-e836.
Embolic strokes of undetermined source (ESUS) account for about a fifth of all ischemic strokes and comprise pathologies including cardioembolic sources, undiagnosed malignancy, and arteriogenic emboli. There is no single strategy for investigating suspected cardioembolic strokes, and initiating empiric anticoagulation for these patients may result in more harm than benefit.
Cardiac monitoring — whether implanted or external — is an important part of a cardioembolic workup, but the ideal timeframe for monitoring is unclear. In the CRYSTAL AF trial, the median time for atrial fibrillation (AF) detection via implanted cardiac monitor (ICM) was 8.4 months. A meta-analysis of ICM use in patients monitored for AF reported detection rates of 5% for <6 months, 26% for 12-24 months, and 34% for >24 months of monitoring. Although prolonged monitoring appears beneficial, the utility may be limited by patient adherence, accurate interpretation of captured rhythms, and patient cost.
Cardiac imaging modalities to investigate suspected cardioembolic stroke include TTE, TEE, cardiac CT, and cardiac MRI. TTE is preferred when left ventricular (LV) thrombus is suspected, while TEE is superior for investigating patent foramen ovale (PFO), aortic atheroma, left atrial (LA) thrombus, prosthetic valve abnormalities, atrial septal abnormalities, and some cardiac tumors. Imaging findings such as LV wall motion abnormalities, LV diastolic dysfunction, LA size, LA shape, LA dysfunction, and LA fibrosis have been associated with stroke.
Clinical risk factors for cardioembolic stroke include prosthetic heart valves, infective endocarditis, aortic arch atheroma, LV dysfunction, PFO, recent myocardial infarct (MI), and atrial arrhythmia/dysfunction. Prior MI, active malignancy, and LV dysfunction (EF≤40%) have been associated with LV thrombus formation. The Risk of Paradoxical Embolism (RoPE) score can be used to assess the likelihood that a documented PFO resulted in a cryptogenic stroke. Several risk stratification scores have been developed to assess for AF in the setting of cryptogenic stroke, including the HAVOC, AS5F, STAF, iPAB, Brown ESUS-AF, and AF-ESUS scores (see Figure 3).
Investigating suspected cardioembolic stroke should be tailored to patients and may be guided by study findings, clinical predictors, and/or risk stratification scores. Ongoing and future studies may refine cardioembolic risk stratification strategies, particularly regarding optimal duration for cardiac monitoring (MonDAFIS), secondary prevention with antiplatelet or anticoagulant (ATTICUS and ARCADIA), and management algorithms (Catch-up-ESUS).
Nice summary. A few points to consider:
1) The clinical benefit of long-term ICM is still unclear. Trials such as CRYSTAL-AF, STROKE-AF and PER DIEM that showed benefit had non-clinical primary outcome measures such as rate of AF detection and increased anticoagulant use, not stroke reduction. Unfortunately, MonDAFIS has the same issue.
2) The LOOP study showed that despite increased AF detection and anticoagulant use with ICM, there was no significant benefit of stroke risk reduction (Lancet. 2021 Oct 23;398(10310):1507-1516.).
The clinical significance of AF detected by long-term ICM is still unclear.