The Brain Heart Interaction in Acute Stroke
The Brain Heart Interaction in Acute Stroke
Many studies have shown that acute cerebral dysfunction can impair cardiac function and
 autonomic control of blood pressure, heart rate and vascular tone, however, the size of the
 stroke is rarely reported. Involvement of the insular cortex seems to predispose to cardiac
 damage and autonomic dysfunction. However, it is not clear whether cardiac dysfunction is
 merely a marker of large strokes or location of the stroke is critical.
Background

 On one hand structural cardiac anomalies and arrhythmias such as atrial fibrillation can give
 rise to thrombi that are dislodged as emboli to the brain and cause stroke. On the other hand
 acute emotional stress or cerebral events can cause acute cardiac dysfunction with left
 ventricular failure in the absence of cardiac causes. The extreme variant of stress
 cardiomyopathy is known as Takotsubo cardiomyopathy. Patients are presenting with chest pain,
 electrocardiographic changes similar to acute myocardial infarction with ST-segment
 elevation, T-wave inversion, or QT prolongation, and elevated cardiac biomarkers such as CK
 and troponin. When coronary angiography is performed coronary arteries are normal, but the
 left ventricle shows mostly apical and midventricular dyskinesia and apical ballooning or
 rarely basal akinesia and apical hyperkinesia. The exact pathogenesis is unknown. Presumably
 high catecholamine levels resulting from the extreme emotional stress or acute cerebral
 events cause severe peripheral vasospasms resulting in myocardial dysfunction.

 It has been known for many decades that myocardial damage such as small patchy necroses and
 subendocardial hemorrhages and cardiac arrhythmias can occur after subarachnoid or
 intracerebral haemorrhage. Greenhout and Reichenbach and Weidler observed abnormally
 increased autonomic activity or an imbalance between parasympathetic and sympathetic input to
 the heart. Systematic analyses of heart and brain interactions were first performed by JW
 Norris and coworkers in Toronto. They examined cardiac enzymes in 230 acute stroke patients
 and found raised CK-MB in 25 (11%). They also found that catecholamine concentrations in
 stroke patients were higher than in controls, that patients with higher CK levels had higher
 norepinephrine levels, more often arrhythmias and such elevated CK and norepinephrine levels
 were more common in hemispheric compared to brain stem strokes. DiAngelantonio et al assessed
 cardiac troponin I levels on admission of 330 stroke patients. When troponin I levels were
 elevated the odds for in-hospital death or non-fatal cardiac events were increased. These
 results were corroborated in a systematic review of 15 similar studies. According to this
 review troponin was elevated in 18.1% of 2901 stroke patients. Patients with elevated
 troponin levels had an odds ratio of 3.0 (95% CI 1.5-6.2) for showing electrocardiographic
 changes and an odds ratio for death of 2.9 (95% CI 1.7-4.8). Hakan Ay and coworkers addressed
 the question whether stroke in specific brain areas are more prone to cardiac damage. In a
 case control study they analysed diffusion weighted MR images of patients with elevated
 troponin T levels (cTnT) and patients with normal levels to identify voxels with diffusion
 restriction that are associated with troponin elevation. Brain regions that were a priori
 associated with cTnT elevation included the right posterior, superior, and medial insula and
 the right inferior parietal lobule. Among patients with right middle cerebral artery
 infarction, the insular cluster was involved in 88% of patients with and 33% without cTnT
 elevation (odds ratio: 15.00; 95% CI: 2.65 to 84.79). Their findings indicate that the right
 insula is associated with elevated serum cardiac troponin T level indicative of myocardial
 injury. In an additional MR study using diffusion and perfusion imaging the same group of
 researchers found that infarctions encompassing the insula is associated with increased
 conversion of ischemic but potentially viable penumbral tissues into infarction. Unlike Ay et
 al Laowattana and coworkers found left insular stroke associated with an increased risk of
 adverse cardiac outcome and decreased cardiac wall motion compared to stroke in other
 locations and TIA. According to their findings left insular lesions show decreased
 parasympathetic tone and right insular lesions increased sympathetic drive. This results in
 abnormal fluctuations in blood pressure, abnormal circadian blood pressure patterns, higher
 norepinephrine levels and elevated blood pressure in acute stroke. Furthermore, baroreflex
 sensitivity has been found to be reduced after stroke, i.e. autonomic adjustment of heart
 rate and vascular tone to sudden blood pressure changes was compromised. Sykora et al
 demonstrated that baroreflex impairment in acute stroke is not associated with carotid
 atherosclerosis but with insular involvement. In their study both insulae seemed to
 participate in processing the baroreceptor information with the left insula being more
 dominant. Other authors found that there might be a hemispheric dominance of autonomic
 control and that impairment of cardiovascular autonomic control increases with higher NIHSS
 scores. The reason for the neuroanatomic correlation of insular strokes and myocardial injury
 and that middle cerebral artery stroke involving the insula are more prone to growth as found
 by Ay et al is not known. A hypothesis focuses on the tight connections of the insular cortex
 to the limbic system. Phylogenetically the limbic system belongs to the oldest parts of the
 brain. It encompasses a group of gyri and nuclei and interconnections in the center of the
 brain such as amygdala, hippocampus, gyrus cinguli, fornix, anterioventral thalamic nuclei,
 and hypothalamus. The main functions of the limbic system is controlling the endocrine and
 autonomic nervous system, emotional life and behavior, olfaction, pleasure, and short and
 long term memory and learning. Dysautonomia after stroke is independent whether stroke is
 ischemic or hemorrhagic. Similarly, excitation of the cortex in epilepsy can result in
 cardiac dysfunction. Epilepsy can cause ictal tachycardia and bradycardia and ECG changes,
 even if brain imaging does not show any structural abnormality. In addition, more than a
 third of epilepsy patients show ictal bradycardia that would merit insertion of a permanent
 pacemaker. Sudden unexpected death is increased five fold in epilepsy, and especially
 patients with treatment refractory generalised tonic clonic seizures are at risk. One of the
 main reasons might be brain heart interactions with asystole. To summarize, many studies have
 shown that acute cerebral dysfunction can impair cardiac function and autonomic control of
 blood pressure, heart rate and vascular tone, however, the size of the stroke is rarely
 reported. Involvement of the insular cortex seems to predispose to cardiac damage and
 autonomic dysfunction. However, it is not clear whether cardiac dysfunction is merely a
 marker of large strokes or location of the stroke is critical.

 Objective

 The aim of the proposed research is to answer the question whether both size of stroke and
 location are independent predictors of impairment of cardiac function in acute stroke.

 Methods

 This is a retrospective analysis of patients of the Bernese Stroke Data Base who all had a
 full MRI examination at admission. All acute stroke patients will be screened for Troponin
 elevations, abnormal electrocardiograms or both. Patients with primary cardiac causes or
 other reasons for troponin elevations or ECG changes will be handled separately. The study
 patients will be compared to at least 200 control stroke patients without troponin elevations
 and without ECG changes. Infarct location, vessel occlusions and volumes of diffusion
 restriction and perfusion deficit will be assessed on MR images. In a multivariable analysis,
 the investigators will find out whether Troponin elevations and ECG abnormalities are
 associated with infarct location or infarct size or both. In addition, the investigators will
 perform a voxel based analysis for correlation of infarct location and troponin elevations
 and ECG abnormalities.
Inclusion Criteria:

 -  Age ≥16 years

 -  Hospitalized between 2004-2014

 -  Acute MRI imaging performed

 -  ECG on admission

 -  Cardiac lab parameters on admission (TnT, CK, CK-MB)

 Exclusion Criteria

 -  Age <16 years

 -  No acute MRI image

 -  No lab parameters