Cardiac injury commonly occurs in patients after a cerebrovascular event, but it is not fully explainable by preexisting cardiac disease [1]. In a meta-analysis of 2,690 patients, cardiac dysfunction was associated with poor outcomes after subarachnoid hemorrhage (SAH) [2], including increased risk of death [3]. This dysfunction leads to arrhythmias, elevations in cardiac enzymes, and left ventricular (LV) dysfunction [4,5,6]. Previous research has proposed potential mechanisms such as systemic inflammatory immune response, catecholamine surge, hypothalamic–pituitary–adrenal axis, and even gut microbiome dysbiosis [7]. In this article from the current issue of Neurocritical Care, Geraghty et al. [8] investigated early mechanisms about how inflammation contributes to cardiac dysfunction after aneurysmal SAH (aSAH), particularly, the novel relationship between systemic or cardiac-specific inflammation and LV systolic dysfunction.

Retrospective analysis of 256 patients with aSAH identified that 34.7% had systolic dysfunction based on transthoracic echocardiography within 72 h of admission. Patients with LV systolic dysfunction were found to have elevated leukocytes. Statistical analysis found a correlation between total leukocytes, neutrophils, monocytes, and reduced systolic function, whereas only increased monocytes were predictive of hyperdynamic function. Based on the finding that serum monocyte changes can predict LV systolic dysfunction in patients with aSAH, the authors used animal models to further explore the role of monocyte-derived macrophage infiltration directly within heart tissue. The authors induced endovascular perforation in male Sprague–Dawley rats, and heart tissues were collected and stained for macrophage marker Iba-1 two days after surgery. The presence and morphology of macrophages in cardiac tissue were then compared with SAH animals and controls treated with and without fingolimod (FTY), an immunomodulatory agent.

In this study, the authors provide novel evidence of inflammatory changes and their effect on cardiac systolic function in patients with aSAH. They identified leukocyte subpopulation changes and pinpointed monocytes as independent predictors of LV dysfunction. Monocytes provide a more objective and measurable parameter to identify patients with aSAH at risk of cardiac dysfunction as well as a potential target for preventing neurocardiac injury.

Interestingly, the immunomodulatory agent FTY was demonstrated to attenuate cardiac macrophage infiltration with no change of its morphology in SAH animals. This highlights the potential therapeutic value of FTY in reducing cardiac inflammation after aSAH and provides preliminary evidence that FTY may reduce trafficking of monocyte-derived macrophages into cardiac tissue. FTY is known to reduce immune cell activity and is approved for treatment of multiple sclerosis.

Although the authors did a detailed baseline demographic table of patients with SAH in the study and stratified the data by systolic function, it would be beneficial to understand how normal, reduced, and hyperdynamic are defined by providing numerical values for ejection fraction. This would facilitate better comparisons with related studies and enable more effective utilization if a meta-analysis is to be performed.

Additionally, another study to complement the immunohistochemistry data from the animal model would be to measure the systolic functions sonographically. This would allow for a correlation between macrophage infiltration in cardiac tissue and LV dysfunction to be established.

Furthermore, it is unclear whether the location of SAH aneurysm rupture affects the level of inflammation. It is worth noting that the most common site of aneurysms in humans is at anterior circulation, with those located in the anterior and posterior communicating artery being most likely to rupture [9]. It is understandable that perforation of the middle cerebral artery is likely more practical to perform given the straightforward access from the external carotid artery (ECA) without craniectomy. Future studies could investigate if aneurysm location plays a role in inflammation or LV dysfunction, although it is important to mention that no p value was reported for aneurysm location in Table 1 (see Table 1 in [8]).

This article presents evidence for monocyte-driven inflammation as a mediator for cardiac LV dysfunction after aSAH. Serum monocyte count could be used alongside other risk factors such as underlying hypertension, alcohol use, Glasgow Coma Scale, and Hunt-Hess score to develop an algorithm or scoring system for identifying patients with aSAH at risk of reduced or hyperdynamic systolic function on transthoracic echocardiogram. Patients with a high risk of developing cardiac dysfunction on admission could be monitored more closely to reduce the negative outcome from cardiac inflammatory injury in patients with aSAH.