Reader response: Undetermined stroke genesis and hidden cardiomyopathies determined by cardiac magnetic resonance

We read with interest the article by Fonseca et al.,¹ which described the frequency of previously undiagnosed cardiomyopathies in patients with ischemic stroke misclassified as having an undetermined etiology after standard diagnostic workup. The study highlights cardiomyopathies as a potential cause of “cryptogenic” stroke and takes a step forward in understanding embolic strokes of undetermined source (ESUS). First, there is accruing evidence that ESUS constitute a Pandora's box characterized by high heterogeneity in etiology, clinical presentation, and outcome.² Second, occult embolic sources—including paroxysmal atrial fibrillation, atrial cardiopathy, left ventricular disease, cardiac valvulopathies, nonstenosing cervical or intracranial plaques, patent foramen ovale, and cancer—are associated with differences in vascular risk factors, clinical, and neuroimaging features.^3,4 Third, there is major overlap of potential embolic sources in patients with ESUS, and this may help explain the negative results of the recent large randomized controlled trials of secondary prevention.⁵ Accordingly, a research project aimed at providing a comprehensive analysis of ESUS data—by exploring the relationships between baseline variables, including demographics, stroke severity and location, embolic sources, and their surrogate biomarkers—might allow identification of distinct phenotypes based on the underlying pathogenesis and offer a rationale for tailored strategies.