Subarachnoid hemorrhage (SAH) is a common cerebrovascular condition resulting from the rupture of intracranial aneurysms or traumatic brain injury, accounting for 6–10% of stroke cases (1, 2). As a type of cerebral hemorrhage, SAH has garnered significant attention due to its high mortality rate (25–30%) and a considerable incidence of complications (15–20%), such as disturbance of consciousness, physical disability, arrhythmias, and neurogenic pulmonary edema (3, 4). However, there is a lack of effective prognostic indicators for evaluating adverse events in SAH.

Cardiac troponin (cTn) is a specific biomarker used to identify myocardial injury and is commonly employed in the clinical diagnosis of myocardial infarction. Persistently elevated levels of troponin often indicate severe myocardial ischemia. In the diagnosis and treatment of patients with SAH, we observed that many patients presented with elevated troponin levels, which were associated with a poor prognosis and severe complications, such as cerebral vasospasm, myocardial ischemia, and even death. Sahar reported that 33–68% of patients had elevated cTn levels within 48 h after SAH (5). Nevertheless, we found that the majority of SAH patients who had high cTn levels did not actually have myocardial injury. This interesting phenomenon prompted us to explore the mechanism behind elevated cTn levels and the crucial role of serum cTn in SAH.

Growing evidence indicates that subarachnoid hemorrhage causes excessive excitation of the sympathetic nervous system and leads to the release of a large number of catechol hormones, resulting in the contraction of cardiovascular and cerebrovascular vessels (6, 7). As a result, elevated serum cTn levels and a series of SAH complications emerge. In 2015, Zhang first reported that cTn elevation was associated with mortality, disability, and delayed cerebral ischemia (DCI) after SAH through meta-analysis (8). Sahar further supplemented the analysis of cTn and adverse cardiovascular outcomes (5). However, previous studies had small sample sizes and lacked comprehensiveness in studying the complications. Moreover, these studies did not make a distinction between traumatic SAH and aneurysmal SAH (aSAH). Here, we conducted a meta-analysis to explore the predictive value of elevated cardiac troponin for a poor prognosis in aneurysmal subarachnoid hemorrhage (aSAH) and total subarachnoid hemorrhage (toSAH), with the aim of providing a valuable reference for clinical management.

The systematic review and meta-analysis adhered to the PRISMA and AMSTAR guidelines (9, 10).

Subarachnoid hemorrhage (SAH), a type of intracranial hemorrhagic condition, carries significant risks of severe neurological and systemic complications, especially in aneurysmal SAH. As an acute stroke event, aSAH is often associated with high mortality and disability rates. Consciousness disorders, delayed cerebral ischemia, vascular spasms, and cardiopulmonary complications are common adverse events in SAH. However, there is still no effective predictive marker for poor prognosis. In this study, we found that 25.0% of the patients in the aSAH group had elevated levels of cTn. Patients with increased cTn levels had a high risk of experiencing disturbance of consciousness, delayed cerebral ischemia, physical disability, cardiac dysfunction, arrhythmias, abnormal ventricular wall motion, and neurogenic pulmonary edema, as confirmed by the meta-analysis of 33 studies (20 prospective studies and 13 retrospective studies) involving 6,349 patients (15–47). This indicated that there was a pathophysiological connection between elevated levels of cTn and adverse events in SAH.

The mainstream view of the pathophysiological mechanism in SAH is that subarachnoid hemorrhage stimulates the sympathetic nervous system, mainly in the insular cortex (48). It activates the sympathetic nervous pathway to release a large amount of catecholamine hormones, including norepinephrine, epinephrine, and dopamine, which may lead to cardiocerebral vasoconstriction and cardiocerebral ischemic events (48, 49). Cerebral vasospasm can lead to a decreased level of consciousness, physical disability, or even cerebral infarction with further damage. Myocardial ischemia results in elevated serum cTn levels, manifesting as angina or acute myocardial infarction. Vasoconstriction and left ventricular diastolic dysfunction can cause an increase in circulating blood volume, resulting in cardiopulmonary complications (49). In addition, the activation of the hypothalamic–pituitary–adrenal axis in SAH also plays a certain role (46). Thus, it can be seen that high cTn levels and complications after SAH are strongly interconnected, explaining the prognostic value of cTn.

We further confirmed that increased cTn levels were strongly associated with mortality and related complications, not only in SAH with mixed etiology but also in aneurysmal SAH. In traumatic patients, death and disability are mainly related to primary brain injury and secondary intracranial hematoma, rather than subarachnoid hematoma. Therefore, we believe that elucidating the predicted value of cTn in aSAH is highly valuable. The main risk factors for aneurysmal SAH include age over 70 years, the location of the ruptured middle cerebral artery aneurysm, Hunt–Hess level of 4–5, aneurysm diameter greater than 7 mm, early aneurysm re-rupture (within 3 months), intraventricular hemorrhage, acute hydrocephalus, and cerebral vasospasm (50). In addition, you reported that the extent of cTn elevation after SAH was related to Hunt–Hess grading and the size of the ruptured aneurysms (51). These findings suggest that high cTn levels play a significant role in determining the prognosis in aSAH. Elevated cTn levels were also found as an independent risk factor for all-cause mortality in aSAH (19). We verified that high cTn levels were associated with a higher likelihood of mortality, disturbance of consciousness, disability dysfunction, and neurogenic pulmonary edema, which should be recognized by clinicians. In addition, the risk factors for adverse events in aSAH, such as age, Hunt–Hess grading, the level of cTn, acute hydrocephalus, and intraventricular hemorrhage, could be collected and aggregated to accurately assess the prognosis. We believe that the extent of cTn elevation will improve risk stratification in SAH patients, which requires further quantitative analysis based on original clinical data.

Unlike previous studies, we classified cardiac dysfunction into arrhythmia and abnormal ventricular wall movement and found that the main types of arrhythmia after SAH were atrial fibrillation and prolonged QT interval. We also found that elevated cTn can predict arrhythmia and abnormal ventricular wall movement, complementing past research (24). Abnormal ventricular wall motion is one of the most common cardiac complications observed after SAH on echocardiography. Left ventricular diastolic dysfunction can lead to neurogenic pulmonary edema, delayed cerebral ischemia, or cerebral vasospasm. Most notably, Takotsubo syndrome, known as stress cardiopathy, occurs in 2 to 15% of SAH cases and refers to temporary local left ventricular systolic and diastolic dysfunction caused by severe emotional or physical stress (52, 53). Caused by the secretion of adrenal hormones from the adrenal medulla, myocardial ischemia occurs without coronary artery stenosis. Due to its self-limitation and good prognosis, doctors should differentiate it from myocardial infarction caused by coronary atherosclerosis.

Clinical management should begin as soon as possible after subarachnoid hemorrhage. When accompanied by high cTn levels, treatment and monitoring should be more comprehensive. Continuous monitoring of arterial blood pressure, heart rate, oxygen saturation, and central venous pressure is required (7). Frequent ECGs and cardiac and cerebral vascular ultrasounds should be performed to evaluate adverse events. Angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and β-blockers are potential treatment options for SAH (54). Previous studies have suggested that β-receptor blockers can improve the prognosis and effectively alleviate cerebral vascular insufficiency and left ventricular dysfunction caused by subarachnoid hemorrhage (55). However, if QT interval extension and atrioventricular block occur, β receptor blockers are not recommended for use. We believe β-receptor blockers could be selectively applied in patients with increased cTn. Moreover, adrenaline, noradrenaline, dobutamine, milrinone, and isoproterenol should be avoided because they may exacerbate myocardial ischemia. For patients with heart failure, diuretics and vasodilators, such as nitroglycerin, should be used. If atrial fibrillation occurs, timely administration of amiodarone or electro-conversion is necessary to prevent thrombus detachment and cerebral infarction. Mannitol should be used to reduce intracranial pressure, and nimodipine should be used to alleviate cerebral vasospasm. The explanation of the condition and poor prognosis to the families of patients with SAH and elevated cTn should be more targeted. Meanwhile, clinicians should intensify monitoring and consider early intervention strategies for high-risk adverse complications.

This meta-analysis incorporated several methodological advancements compared to previous studies, including a comprehensive analysis of more complications reported in recent literature and a comparative analysis of the predictive ability of cardiac troponin (cTn) between aneurysmal subarachnoid hemorrhage (aSAH) and overall SAH cases. Nevertheless, there are still several limitations in this meta-analysis. First, due to the incomplete original data from the various literature sources, we could not perform a hierarchical analysis, such as dividing the data by gender, age, BMI, and underlying diseases. Second, as this study was a qualitative analysis, it was difficult to determine a specific critical value for cTn elevation. We were unable to analyze the quantitative relationship between elevated cTn levels and the incidence of complications. In addition, other complications after SAH require further investigation. Third, due to the limited original literature on traumatic SAH, we were unable to analyze the relationship between increased cTn levels and prognosis in traumatic SAH. However, we believe that for traumatic patients, primary brain injury and secondary hematoma play a more significant role in determining the prognosis than SAH itself. Finally, as the included studies were from different countries with varying inclusion criteria, the results might have been overestimated after the meta-analysis. However, we used subgroup analysis, heterogeneity analysis, and bias testing to present the most reliable results possibly. We look forward to more clinical research in the future to fill the gap in this field, allowing us to gain a more comprehensive understanding of the predictive value of cTn in SAH, especially aneurysmal SAH.

This meta-analysis indicated a significant positive correlation between elevated cTn levels and adverse outcomes in SAH, including mortality, consciousness disorders, DCI, disability, cardiac dysfunction, and neurogenic pulmonary edema. High levels of cTn play a significant role in predicting the prognostic value in aneurysmal SAH. Cardiac troponin levels should be routinely monitored in patients with SAH, and clinicians should assess the risk of related complications based on elevated cTn levels and provide timely treatment.