Cardiac abnormalities after subarachnoid hemorrhage

Aneurysmal subarachnoid hemorrhage(aSAH) is a devastating neurological disease. During the course of the aSAH several neurological and medical complications may occur. Cardiac abnormalities after aSAH are observed often and resemble stress cardiomyopathy or Tako-tsubo cardiomyopathy(Broken Heart Syndrome) that has been described after acute stress. It is a reversible cardiac dysfunction with distinct imaging features(the echocardiographic or left ventricular angiographic image resembles a Tako-Tsubo which is a Japanese octopus trap). This thesis was based on the question how often cardiac dysfunction occurs in aSAH, what the clinical characteristics are and whether it influences outcome. Second we sought to further investigate Tako-Tsubo cardiomyopathy in a disease where it seemed to occur often: aSAH. We designed a multicenter cohort study(Serial Echocardiography After Subarachnoid Hemorrhage (S.E.A.S.A.H.)) to observe the frequency of cardiac dysfunction, characteristics of the cardiac dysfunction and to investigate prognostic meaning in patients with aSAH. In Chapter 1 the outline of this thesis is described. Furthermore we elaborate on the design of the SEASAH study. In Chapter 2 the results of our meta-analysis are presented. We concluded that troponin and/or NT-proBNP and abnormal echocardiographic findings are associated with an increased risk of death, poor outcome, and delayed cerebral ischemia after subarachnoid hemorrhage. However, many questions remained. So we decided to go forward with the SEASAH study. In Chapter 3 we describe the results of the SEASAH study. In this study we included 301 patients in which we performed serial ECGs, echocardiography and measured troponin and NT-proBNP. We found that echocardiographic wall motion abnormalities were associated with death, DCI and poor outcome, independent of other clinical predictors for outcome. In Chapter 4 we found that WMA may be present on admission or develop during the course of aSAH. Poor neurological condition on admission, sinus tachycardia, ST-depression and ST-elevation at the admission ECG and elevated troponin T, are independent predictors for early WMA, a myocardial infarct pattern on the admission ECG and elevated troponin T in patients with aSAH predict late WMA independent of other clinical predictors. In Chapter 5 data of cerebral CT perfusion was correlated with cardiac data from the SEASAH. We found an association between decreased cerebral blood flow in patients with impaired cardiac function compared to patients with normal cardiac function. In Chapter 6 we describe the results of a histopathological study. In this study we sought for evidence that the mononuclear cellular infiltration that is found in the myocardium of patients with aSAH might be a myocarditis. We compared postmortem myocardium of patients who died from aSAH with controls. We found a markedly increase in inflammatory cells in patient with aSAH. Furthermore, we found evidence of thrombi and myocytolysis. This study supports the theory that catecholaminergic stress causes a myocarditis and gives direction to future research. Finally, in Chapter 7 we summarize the main conclusions of this thesis and put the findings into perspective of literature