Subarachnoid hemorrhage (SAH) involves the rupture of an aneurysm in the deep part of the brain, around the circle of Willis, which disperses blood not within the parenchyma but around the brain. Despite this absence of parenchymal interaction, SAH is more potentially damaging than almost any other bleeding syndrome in the brain. Because of its association with heart disease, SAH has been at the nexus of investigation into heart-brain connections for a long time. As early as the 1940s and 1950s, a high incidence of cardiac problems, particularly electrocardiographic (ECG) abnormalities, was described in patients with SAH, especially in those with aneurysmal SAH.
SAH serves as a good model for studying heart-brain interactions because it is associated with both a high incidence of arrhythmia and a low prevalence of coronary heart disease. In a review of five major retrospective studies involving intervention for nontraumatic SAH, Lanzino and colleagues found that 91% of patients had evidence of atrial or ventricular arrhythmias on ECG.1 In a prospective study of 223 patients with SAH, Tung and colleagues found a low prevalence (5%) of preexisting cardiac disease.2 This latter finding suggests that the cardiac findings in patients with SAH are a unique phenomenon likely attributable to SAH itself, and this scarcity of confounding cardiac factors makes SAH an ideal model for heart-brain investigations. This review will discuss cardiac responses to cerebral injury in SAH and then look ahead to the use of a novel murine model of SAH to further examine these responses and explore their potential inflammatory underpinnings.
CARDIAC RESPONSES TO CEREBRAL INJURY IN PATIENTS WITH SUBARACHNOID HEMORRHAGE
Cardiac arrhythmias associated with SAH are common and well classified. Sakr and colleagues found rhythm abnormalities in 30.2% of 106 patients with SAH and an abnormal ECG; the most common rhythm abnormality was sinus bradycardia (16%), followed by sinus tachycardia (8.5%) and other arrhythmias (5.7%), which included ventricular premature contraction, ventricular bigeminy, and atrial fibrillation.3
Multifocal ventricular tachycardia (torsades de pointes) is associated with a high mortality rate and is a feared complication of SAH, but its importance has been called into question recently. Although Machado and colleagues found in a review of the literature that torsades de pointes occurred in 5 of 1,139 patients with SAH (0.4%), they were unable to rule out confounding factors (ie, hypokalemia and hypomagnesemia) as the cause of the arrhythmia.4 In a supportive finding, van den Bergh et al reported that QT intervals in patients with SAH are actually shorter when serum magnesium levels are lower (prolonged intervals are thought to indicate elevated risk for multifocal ventricular tachycardia).5 Although it is clear that patients with SAH frequently have a prolonged QT interval (discussed later), which is thought to be a risk factor for torsades de pointes, the electrolyte abnormalities seen in patients with SAH make it hard to definitively attribute the arrhythmia to the direct action of the brain.
Cardiac changes that resemble ischemia
Certain ECG changes seen in patients with SAH are referred to as ischemic changes because of their resemblance to ECG changes seen in acute coronary artery occlusion. In SAH, there is evidence that acute coronary artery occlusion is not present. The myocardial changes are assumed to be due to subendocardial ischemia. ECG abnormalities usually disappear within a few days or without resolution of the neurologic or cardiac condition. They are considered markers of the severity of SAH but not predictors for potentially serious cardiac complications or clinical outcomes.5
Repolarization abnormalities, also commonly seen in coronary artery ischemic disease, are common in SAH. Sakr et al found that 83% of patients with SAH developed repolarization abnormalities, with the most common being T-wave changes (39%) and the presence of U waves (26%).3 Deep, symmetric inverted T waves, usually without much ST-segment elevation or depression, are the typical abnormality. Left bundle branch block, which is sometimes considered a marker of acute, large-vessel ischemia, was present in only 2% of patients.3
Prolonged QT intervals were found in 34% of patients in the study by Sakr et al.3 The presence of this prolonged segment has become the most looked-for clinical tool for determining who might be at risk for cardiomyopathy. Although there is little evidence that the cardiomyopathy seen after SAH is associated closely with prolongation of the QT interval, it is a simple bedside sign that is readily available to all practitioners, given the practice of obtaining an ECG in almost all hospitalized patients at the time of admission.
In older patients with SAH, ECG changes occur with more severe events. In a retrospective study, Zaroff et al identified 439 patients with SAH, 58 of whom had ECG findings indicative of ischemia or myocardial infarction within 3 days of presentation and before surgery to correct an aneurysm.6 The most common ECG abnormality was T-wave inversions; the next most common abnormalities were ST depression, ST elevation, and Q waves of unknown duration. The most common pattern for ECG abnormalities suggests abnormalities in the anterior descending artery territory or in multiple vascular territories. Follow-up tracings demonstrating reversal of the abnormalities were available for 23 of the 58 patients (40%). There was no significant association between any specific ECG abnormality and mortality. Compared with patients with negative ECG findings, the patients with positive ECG findings were significantly older (mean age, 62 ± 15 years vs 53 ± 14 years), had a higher mean Hunt and Hess grade, and had higher all-cause mortality. Surprisingly, aneurysm location did not differ significantly between the two groups. These data suggest that coronary artery disease (which would be more common in the older population) may be a contributing factor to mortality.