Insular damage, death and newly diagnosed atrial fibrillation in intracerebral hemorrhage: stroke‐induced heart injury as the potential missing link

The insula exerts a strong influence on the autonomic regulation of heart rhythm. Involvement of the insular cortex has been associated with both an increased risk of post-ischemic stroke death [1] and atrial fibrillation (AF) newly detected after stroke (AFDAS) [2]. Much less is known about outcomes and the incidence of AFDAS related to insular damage in patients with acute intracerebral hemorrhage (ICH). In this issue of the European Journal of Neurology, Prats-S anchez et al. [3] report a significant association between insular involvement and an increased risk of death in a retrospective cohort study of 347 consecutive patients presenting with ICH. Damage to the insular cortex was also associated with a new diagnosis of AF. At 3 months, 40% of the patients had died. After multivariable analysis, insular damage had the strongest association with death (odds ratio, 3.98), even relative to variables consistently associated with poor outcomes, such as age, the Glasgow Coma Scale score and the presence of intraventricular hemorrhage. After excluding participants with early death, known AF, insufficient electrocardiographic monitoring and recent ischemic stroke, the proportion of patients with an AFDAS lasting at least 30 s, with a median of 6 days of continuous electrocardiographic monitoring, was 6.0% (11/183). Damage to the insular cortex was independently associated with AFDAS, showing a sevenfold higher risk than patients without insular involvement. The association between insular involvement and death in patients with ICH is in keeping with the results from a study by Lee et al. [4] examining the relationship between hematoma location and death, in which the posterior insula was significantly associated with higher risk of death among patients with lobar ICH. Lee et al. [4] used voxel-based lesion-symptom mapping to link lesion location to the odds of death, which allows for a more accurate assessment of the association between lesion location and a given variable than the pragmatic approach used by PratsS anchez et al. [3]. The association of insular damage with increased mortality was not explained by cardiovascular causes. However, the number of cardiovascular deaths was surprisingly low, possibly related to the lack of systematic adjudication for every cause of death. Most patients died in hospital (180/210 deaths) and deaths were classified based on the review of medical reports, which were not available for patients dying after discharge. Therefore, cardiovascular causes, which are known to be relatively more prevalent in the long-term than immediately after stroke, could not be ruled out. Right dorsal anterior insular infarctions have been independently associated with myocardial injury [5]. This stroke-induced heart injury (SIHI) is probably explained by autonomic imbalances [6] leading to catecholamine surges. Other potential mechanisms include systemic inflammation [6], vagusmediated local inflammatory changes [7] and even changes to the microbiome, microvesicles and microRNA [7]. With regard to non-cardiovascular mechanisms, considering the eloquent cortex neighboring the insula and the high density of insular afferent and efferent projections, higher rates of comorbid disability (e.g. dysphagia leading to aspiration pneumonia) may have contributed to the increased mortality noted. This study deserves special attention as it is unique in its examination of the association between insular involvement and AFDAS in patients with ICH. The elevated risk of AFDAS may be explained by SIHI or some of its proposed underlying mechanisms [6]. As cardiac structural changes involve the subendocardium, they could potentially affect the cardiac-conducting system, ultimately triggering AF. Importantly, unlike studies conducted among ischemic stroke patients, AFDAS in patients with ICH is less likely to be pre-existing subclinical arrhythmias. A new diagnosis of AF following an insular ischemic stroke could prompt the controversy of which came first (cardiogenic vs. neurogenic AF). However, the increased risk of AFDAS associated with post-ICH insular involvement, a seemingly unrelated consequence, further supports the possibility of SIHI leading to neurogenic