Left ventricular non-compaction as a potential source for cryptogenic ischemic stroke in the young: A case-control study

BACKGROUND: Up to 50% of ischemic strokes in the young after thorough diagnostic work-up remain cryptogenic or associated with low-risk sources of cardioembolism such as patent foramen ovale (PFO). We studied with cardiac magnetic resonance (CMR) imaging, whether left ventricular (LV) non-compaction—a possible source for embolic stroke due to sluggish blood flow in deep intertrabecular recesses—is associated with cryptogenic strokes in the young. METHODS: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is an international prospective multicenter case-control study of young adults (aged 18–49 years) presenting with an imaging-positive first-ever ischemic stroke of undetermined etiology. In this pilot substudy, 30 cases and 30 age- and sex-matched stroke-free controls were examined with CMR. Transcranial Doppler (TCD) bubble test was performed to evaluate the presence and magnitude of right-to-left shunt (RLS). RESULTS: There were no significant differences in LV volumes, masses or systolic function between cases and controls; none of the participants had non-compaction cardiomyopathy. Semi-automated assessment of LV non-compaction was highly reproducible. Non-compacted LV mass (median 14.0 [interquartile range 12.6–16.0] g/m(2) vs. 12.7 [10.4–16.6] g/m(2), p = 0.045), the ratio of non-compacted to compacted LV mass (mean 25.6 ± 4.2% vs. 22.8 ± 6.0%, p = 0.015) and the percentage of non-compacted LV volume (mean 17.6 ± 2.9% vs. 15.7 ± 3.8%, p = 0.004) were higher in cases compared to controls. In a multivariate conditional logistic regression model including non-compacted LV volume, RLS and body mass index, the percentage of non-compacted LV volume (odds ratio [OR] 1.55, 95% confidence interval [CI] 1.10–2.18, p = 0.011) and the presence of RLS (OR 11.94, 95% CI 1.14–124.94, p = 0.038) were independently associated with cryptogenic ischemic stroke. CONCLUSIONS: LV non-compaction is associated with a heightened risk of cryptogenic ischemic stroke in young adults, independent of concomitant RLS and in the absence of cardiomyopathy. CLINICAL TRIAL REGISTRATION: SECRETO; NCT01934725. Registered 4(th) September 2013. https://clinicaltrials.gov/ct2/show/NCT01934725