Brain-heart Axis Research Articles

“We have dealt with so much. There’s more coming?”: Improving Knowledge About Brain Health in Adults Living With Congenital Heart Disease

BackgroundSignificant advances in managing congenital heart disease (CHD) have occurred over the past few decades, resulting in a fast-growing adult patient population with distinct needs requiring urgent attention. Research has recently highlighted the prevalence of neurocognitive differences among adults living with CHD. Yet, there is a lack of knowledge about the perspectives of people living with CHD and family members/caregivers on brain health. We sought to explore their perspectives to guide future research and clinical endeavours. MethodsUsing the principles of integrated knowledge translation and qualitative interpretive description, we conducted 2 focus groups with 7 individuals with CHD and their family members as part of a virtual forum on brain health in CHD. Data analysis followed the principles of interpretive description. ResultsA lack of understanding about overall brain health and neurocognitive differences in adult CHD was identified. To increase overall knowledge about brain health, initiatives should (1) focus on the individual living with CHD, involving family members and peers; (2) use social media and health care encounters for knowledge exchange; and (3) ensure a “balancing act” in the information provided to avoid feelings of worry and uncertainty about the future while simultaneously empowering people living with CHD. ConclusionsThere is a pressing need for better education about brain health among individuals living with CHD. Our findings can guide clinicians in developing programmes of care and (re)design health services that address the brain-heart axis and neurocognitive differences in CHD.

Association between cognitive impairment and risk of atrial fibrillation: The Atherosclerosis Risk in Communities study.

Atrial fibrillation (AF) is reportedly a risk factor for cognitive impairment. Interestingly, recent studies have emphasized that impaired cognition is probably an initiating factor of cardiovascular disease. Thus, we aimed to explore the association between impaired cognition and the risk of AF, and clarify the potential mechanisms. Participants of visit 2 (1991-1993) in the Atherosclerosis Risk in Communities study were included. Global cognition z-scores and factor scores were calculated using the word fluency, delayed word recall, and digit symbol substitution tests. AF incidents were diagnosed by electrocardiography and inpatient records. The association of cognitive decline with AF risk and left atrial volume index (LAVI) was explored using Cox proportional hazards and linear regression models, respectively. During the median follow-up of 18.2 ± 6.2 years, 2056/11,675 (17.6%) participants developed AF. Participants in the lowest quartile of global cognition z- and factor scores had a higher risk of AF (hazard ratio [HR]: 1.271, 95% confidence interval [CI]: 1.094-1.477, p = 0.002; HR: 1.305, 95% CI: 1.110-1.535, p = 0.001, respectively) than those in the highest quartile. Global cognition z- and factor scores were negatively correlated with the LAVI (B: -0.411, 95% CI: -0.749 to -0.074, p = 0.017; B: -0.425, 95% CI: -0.833 to -0.017, p = 0.041, respectively). Cognitive decline is significantly associated with a higher risk of AF, with atrial remodeling being a potential mechanism. Our results extend previous findings of the brain-heart axis and indicate the effects of cognitive injury on cardiac function and structure. URL: https://www. gov; unique identifier: NCT00005131.

Microstates of the cortical brain-heart axis.

Electroencephalographic (EEG) microstates are brain states with quasi-stable scalp topography. Whether such states extend to the body level, that is, the peripheral autonomic nerves, remains unknown. We hypothesized that microstates extend at the brain-heart axis level as a functional state of the central autonomic network. Thus, we combined the EEG and heartbeat dynamics series to estimate the directional information transfer originating in the cortex targeting the sympathovagal and parasympathetic activity oscillations and vice versa for the afferent functional direction. Data were from two groups of participants: 36 healthy volunteers who were subjected to cognitive workload induced by mental arithmetic, and 26 participants who underwent physical stress induced by a cold pressure test. All participants were healthy at the time of the study. Based on statistical testing and goodness-of-fit evaluations, we demonstrated the existence of microstates of the functional brain-heart axis, with emphasis on the cerebral cortex, since the microstates are derived from EEG. Such nervous-system microstates are spatio-temporal quasi-stable states that exclusively refer to the efferent brain-to-heart direction. We demonstrated brain-heart microstates that could be associated with specific experimental conditions as well as brain-heart microstates that are non-specific to tasks.

A new perspective on HIV: effects of HIV on brain-heart axis.

The human immunodeficiency virus (HIV) infection can cause damage to multiple systems within the body, and the interaction among these various organ systems means that pathological changes in one system can have repercussions on the functions of other systems. However, the current focus of treatment and research on HIV predominantly centers around individual systems without considering the comprehensive relationship among them. The central nervous system (CNS) and cardiovascular system play crucial roles in supporting human life, and their functions are closely intertwined. In this review, we examine the effects of HIV on the CNS, the resulting impact on the cardiovascular system, and the direct damage caused by HIV to the cardiovascular system to provide new perspectives on HIV treatment.

Towards the definition of Microstates of the Cortical Brain-Heart Axis.

Brain microstates are defined as states with quasi-stable scalp activity topography and have been widely studied in literature. Whether those states are brain-specific or extend to the body level is unknown yet. We investigate the extension of cortical microstates to the peripheral autonomic nerve, specifically at the brain-heart axis level as a functional state of the central autonomic network. To achieve this, we combined Electroencephalographic (EEG) and heart rate variability (HRV) series from 36 healthy volunteers undergoing a cognitive workload elicitation after a resting state. Our results showed the existence of microstates at the functional brain-heart axis with spatio-temporal and quasi-stable states that exclusively pertained to the efferent direction from the brain to the heart. Some of the identified microstates are specific for neural or cardiovascular frequency bands, while others topographies are recurrent over the EEG and HRV spectra. Furthermore, some of the identified brain-heart microstates were associated with specific experimental conditions, while others were nonspecific to tasks. Our findings support the hypothesis that EEG microstates extend to the brain-heart axis level and may be exploited in future neuroscience and clinical research.

Depression as a cardiovascular disorder: central-autonomic network, brain-heart axis, and vagal perspectives of low mood.

If depressive symptoms are not caused by the physiological effects of a substance or other medical or neurological conditions, they are generally classified as mental disorders that target the central nervous system. However, recent evidence suggests that peripheral neural dynamics on cardiovascular control play a causal role in regulating and processing emotions. In this perspective, we explore the dynamics of the Central-Autonomic Network (CAN) and related brain-heart interplay (BHI), highlighting their psychophysiological correlates and clinical symptoms of depression. Thus, we suggest that depression may arise from dysregulated cardiac vagal and sympathovagal dynamics that lead to CAN and BHI dysfunctions. Therefore, treatments for depression should target the nervous system as a whole, with particular emphasis on regulating vagal and BHI dynamics.

Denervation or stimulation? Role of sympatho-vagal imbalance in HFpEF with hypertension.

Heart failure (HF) in the elderly is an increasingly large and complex problem in modern society. Notably, the cause of HF with preserved ejection fraction (HFpEF) is multifactorial and its pathophysiology is not fully understood. Among these, hypertension has emerged as a pivotal factor in the pathophysiology and therapeutic targets of HFpEF. Neuronal elements distributed throughout the cardiac autonomic nervous system, from the level of the central autonomic network including the insular cortex to the intrinsic cardiac nervous system, regulate the human cardiovascular system. Specifically, increased sympathetic nervous system activity due to sympatho-vagal imbalance is suggested to be associated the relationship between hypertension and HFpEF. While several new pharmacological therapies, such as sodium-glucose cotransporter 2 inhibitors, have been shown to be effective in HFpEF, neuromodulatory therapies of renal denervation and vagus nerve stimulation (VNS) have received recent attention. The current review explores the pathophysiology of the brain-heart axis that underlies the relationship between hypertension and HFpEF and the rationale for therapeutic neuromodulation of HFpEF by non-invasive transcutaneous VNS.

Noradrenergic pathway from the locus coeruleus to heart is implicated in modulating SUDEP

Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death among epilepsy patients. However, the underlying mechanism remains elusive. Seizure-induced respiratory arrest (S-IRA) is recognized as a main cause of SUDEP, but the contribution of other factors such as cardiac arrhythmias cannot be excluded. Here, we found that both the locus coeruleus (LC) and peripheral noradrenergic neurotransmission were involved in S-IRA and the protective effect of atomoxetine in reducing the occurrence of S-IRA and SUDEP could be reversed by esmolol hydrochloride. Moreover, we investigated the connection between the LC and heart implicated in the modulation of SUDEP by fiber photometry. These data suggested that noradrenergic neurons in the LC might regulate the occurrence of SUDEP through β1-adrenergic receptors on cardiomyocytes. Overall, our findings indicate the involvement of the brain-heart axis in modulating S-IRA and SUDEP and, therefore, will open a new perspective on decoding SUDEP.

Cerebral amyloid angiopathy-related cardiac injury: Focus on cardiac cell death.

Cerebral amyloid angiopathy (CAA) is a kind of disease in which amyloid β (Aβ) and other amyloid protein deposits in the cerebral cortex and the small blood vessels of the brain, causing cerebrovascular and brain parenchymal damage. CAA patients are often accompanied by cardiac injury, involving Aβ, tau and transthyroxine amyloid (ATTR). Aβ is the main injury factor of CAA, which can accelerate the formation of coronary artery atherosclerosis, aortic valve osteogenesis calcification and cardiomyocytes basophilic degeneration. In the early stage of CAA (pre-stroke), the accompanying locus coeruleus (LC) amyloidosis, vasculitis and circulating Aβ will induce first hit to the heart. When the CAA progresses to an advanced stage and causes a cerebral hemorrhage, the hemorrhage leads to autonomic nervous function disturbance, catecholamine surges, and systemic inflammation reaction, which can deal the second hit to the heart. Based on the brain-heart axis, CAA and its associated cardiac injury can create a vicious cycle that accelerates the progression of each other.

Disrupted resting-state functional connectivity of the thalamus in patients with coronary heart disease

BackgroundAlthough homeostasis of the cardiovascular system is regulated by the cerebral cortex via the autonomic nervous system, the role of abnormal brain functional connectivity (FC) networks in patients with cardiac dysfunction remains unclear. Here, we report thalamus-based FC alterations and their relationship with clinical characteristics in patients with coronary heart disease (CHD). MethodsWe employed resting-state functional magnetic resonance imaging (rs-fMRI) to acquire imaging data in twenty-six patients with CHD alongside sixteen healthy controls (HCs). Next, we performed a thalamus-based FC analysis to profile abnormal FC patterns in the whole brain. Subsequently, the mean time series of the brain regions that survived in the FC analysis were used to determine correlations with clinical parameters in patients with CHD. ResultsWe found no statistically significant differences in demographic and clinical data between patients with CHD and HCs. Patients with CHD showed decreased FC patterns between bilateral thalami and left hemisphere, encompassing supplementary motor area, superior frontal gyrus, superior parietal gyrus, inferior parietal gyrus, middle cingulate cortex, lingual gyrus and calcarine sulcus. ConclusionsThese findings not only have implications in clarifying the relationship between cerebral functional imbalance and cardiovascular system, but also provide valuable insights to guide future evaluation and management of cardiac autonomic regulation via the brain-heart axis.

Glial cell activity in cardiovascular diseases and risk of acute myocardial infarction

Growing evidence indicates that the pathophysiological link between the brain and heart underlies cardiovascular diseases, specifically acute myocardial infarction (AMI). Astrocytes are the most abundant glial cells in the central nervous system and provide support/protection for neurons. Astrocytes and peripheral glial cells are emerging as key modulators of the brain-heart axis in AMI, by affecting sympathetic nervous system activity (centrally and peripherally). This review, therefore, aimed to gain an improved understanding of glial cell activity and AMI risk. This includes discussions on the potential role of contributing factors in AMI risk, i.e., autonomic nervous system dysfunction, glial-neurotrophic and ischemic risk markers [glial cell line-derived neurotrophic factor (GDNF), astrocytic S100 calcium-binding protein B (S100B), silent myocardial ischemia, and cardiac troponin T (cTnT)]. Consideration of glial cell activity and related contributing factors in certain brain-heart disorders, namely, blood-brain barrier dysfunction, myocardial ischemia, and chronic psychological stress, may improve our understanding regarding the pathological role that glial dysfunction can play in the development/onset of AMI. Here, findings demonstrated perturbations in glial cell activity and contributing factors (especially sympathetic activity). Moreover, emerging AMI risk included sympathovagal imbalance, low GDNF levels reflecting prothrombic risk, hypertension, and increased ischemia due to perfusion deficits (indicated by S100B and cTnT levels). Such perturbations impacted blood-barrier function and perfusion that were exacerbated during psychological stress. Thus, greater insights and consideration regarding such biomarkers may help drive future studies investigating brain-heart axis pathologies to gain a deeper understanding of astrocytic glial cell contributions and unlock potential novel therapies for AMI.

Acute right insular ischaemic lesions and poststroke left ventricular dysfunction

IntroductionMyocardial injury related to acute ischaemic stroke is common even without primary cardiac disease. We intended to determine associations between values of left ventricular ejection fraction (LVEF) and ischaemic stroke...

Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management

Broken Heart Syndrome, also known as Takotsubo Syndrome (TS), is sudden and transient dysfunction of the left and/or right ventricle which often mimics Acute Coronary Syndrome (ACS). Japan was the first country to describe this syndrome in the 1990s, and since then it has received a lot of attention from researchers all around the world. Although TS was once thought to be a harmless condition, recent evidence suggests that it may be linked to serious complications and mortality on par with Acute Coronary Syndrome (ACS). The understanding of TS has evolved over the past few years. However, its exact etiology is still poorly understood. It can be classified into two main types: Primary and Secondary TS. Primary TS occurs when the symptoms of myocardial damage, which is typically preceded by emotional stress, are the reason for hospitalization. Secondary TS is seen in patients hospitalized for some other medical, surgical, obstetric, anesthetic, or psychiatric conditions, and the dysfunction develops as a secondary complication due to the activation of the sympathetic nervous system and the release of catecholamines. The etiopathogenesis is now proposed to include adrenergic hormones/stress, decreased estrogen levels, altered microcirculation, endothelial dysfunction, altered inflammatory response via cardiac macrophages, and disturbances in the brain-heart axis. The role of genetics in disease progression is becoming the focus of several upcoming studies. This review focuses on potential pathophysiological mechanisms for reversible myocardial dysfunction observed in TS, and comprehensively describes its epidemiology, clinical presentation, novel diagnostic biomarkers, and evolving principles of management. We advocate for more research into molecular mechanisms and promote the application of current evidence for precise individualized treatment.

Abstract 14807: Effect of Psychiatric Illnesses on the Stress Induced Cardiomyopathy Readmission

Introduction: Stress-induced cardiomyopathy (SIC) is a form of transient non-ischemic cardiomyopathy that is precipitated in the setting of acute emotional or physical stress. Postulated hypothesis implicated catecholaminergic excess and a role of the brain-heart axis behind its pathogenesis. The impact of different psychiatric illnesses on the outcomes of SIC is not clear. Method: We conducted a retrospective study using National Readmission Database (NRD) from 2011 to 2019 using ICD-10-CM (International Classification of Diseases, 10th Edition, Clinical Modification) and ICD-9-CM codes to identify the admissions with the discharge diagnosis of SIC and stratified them based on the presence of psychiatric illnesses. The primary outcome was six-month readmission and predictors of readmission. Result: We included a total of 98,721 admissions with a diagnosis of SIC. Among them, 12.9% had major depression, 1.8% had bipolar disorder, 17.6% had an anxiety disorder, and 0.6% had schizophrenia. Overall, patients with psychiatric illnesses were younger. Patients with psychiatric illnesses had a higher burden of comorbidities. Patients with schizophrenia had higher in-hospital mortality. Patients with psychiatric illnesses had a higher likelihood of getting readmitted within six months (p<0.001). The significant independent positive predictors of readmission within 6 months were history of diabetes [odds ratio (OR):1.21, confidence interval (CI):1.16-1.26], heart failure (OR:1.31, CI:1.26-1.36), CKD/ESRD (OR: 1.44, CI:1.37-1.51), AF (OR: 1.25, CI:1.20-1.31), anemia (OR:1.24, CI: 1.15-1.34), peripheral arterial disease (OR: 1.25, CI:1.18-1.33), chronic obstructive pulmonary disease (OR: 1.35, CI:1.29-1.40), and prior stroke (OR: 1.10, CI: 1.02-1.18). Conclusion: We witnessed that psychiatric illnesses were associated with a higher likelihood of six-month readmission in patients with SIC.

Neurovisceral interactions within the brain-heart axis as the basis of neurocardiology

The use of a systematic approach to the study of the etiology of a certain pathology makes it possible to improve the understanding of its pathogenesis, as well as to develop more effective diagnostic and therapeutic approaches, including improving the prediction of its risk. Within this review, we will consider such an area of interdisciplinary research as neurocardiology, which studies the brain-heart axis. Examples of cardiovascular diseases associated with organic and functional disorders of this axis will be considered, as well as the prospects for research in this area and their translational significance for clinical medicine.

Neurometabolism and Ventricular Dyssynchrony in Patients With Heart Failure and Reduced Ejection Fraction

BackgroundThe brain coordinates the heart through the autonomic nervous system (ANS). Numerous mediator signals along the brain-heart axis interact with the neuronal-metabolic system in heart failure (HF). Disturbances in cardio-neural interactions influence the disease progression in patients with HF. ObjectivesThe purpose of this study was to investigate the interactome between ANS-associated neurometabolism and ventricular dyssynchrony in patients with heart failure with reduced ejection fraction (HFrEF). Further, we studied the association of neurometabolism with major arrhythmic events (MAEs). MethodsA total of 197 patients with HFrEF who underwent gated single-photon emission computed tomography myocardial perfusion imaging and the brain 18F-fluorodeoxyglucose positron emission tomography/computed tomography were prospectively enrolled. Relationships between the brain metabolism and MAEs were assessed using Cox models and mediation analyses. Finally, metabolic central autonomic networks were constructed and statistically compared between patients with and without MAEs. ResultsIn total, 35 (17.8%) patients experienced MAEs during a median follow-up of 3.1 years. In patients with HFrEF (age 58 years [IQR: 50-64 years], left ventricular ejection fraction: 20.0% [IQR: 15.0%-25.0%]), glucose hypometabolism in the insula, hippocampus, amygdala, cingulate gyrus, and caudate nucleus were independent predictors for MAEs (all P < 0.05). Cerebral hypometabolism was related to ventricular dyssynchrony, which was the predominant risk factor of MAEs. Additionally, patients who experienced MAEs presented hypoconnectivity in the metabolic central autonomic network compared with those without MAEs (P < 0.05). ConclusionsWe found an interaction of the neuronal metabolic-ventricular dyssynchronization axis in HF, which might be related to MAEs. This new brain-heart axis could expand our understanding of the distinct pathomechanisms of HFrEF.

Das Takotsubo-Syndrom

TTS is an acute heart failure syndrome that usually affects postmenopausal women. The Syndrome is often preceded by an emotional or physical trigger. TTS strongly resembles acute myocardial infarction from a clinical standpoint and also exhibits ECG changes in the same proportion. There are specific patterns of wall motion abnormalities, based on which, the syndrome can be divided into four types. Neurological and/or psychiatric comorbidities are common in TTS patients. Therapy is based on the hemodynamic state and the presence of left ventricular outflow tract obstruction or cardiogenic shock. TTS has a comparable mortality to acute myocardial infarction. Pathophysiologically, the activation of the brain-heart axis with acute catecholamine storm seems to inherit a central role.

Molecular imaging of the brain–heart axis provides insights into cardiac dysfunction after cerebral ischemia

Ischemic stroke imparts elevated risk of heart failure though the underlying mechanisms remain poorly described. We aimed to characterize the influence of cerebral ischemic injury on cardiac function using multimodality molecular imaging to investigate brain and cardiac morphology and tissue inflammation in two mouse models of variable stroke severity. Transient middle cerebral artery occlusion (MCAo) generated extensive stroke damage (56.31 ± 40.39 mm3). Positron emission tomography imaging of inflammation targeting the mitochondrial translocator protein (TSPO) revealed localized neuroinflammation at 7 days after stroke compared to sham (3.8 ± 0.8 vs 2.6 ± 0.7 %ID/g max, p < 0.001). By contrast, parenchyma topical application of vasoconstrictor endothelin-1 did not generate significant stroke damage or neuroinflammatory cell activity. MCAo evoked a modest reduction in left ventricle ejection fraction at both 1 weeks and 3 weeks after stroke (LVEF at 3 weeks: 54.3 ± 5.7 vs 66.1 ± 3.5%, p < 0.001). This contractile impairment was paralleled by elevated cardiac TSPO PET signal compared to sham (8.6 ± 2.4 vs 5.8 ± 0.7%ID/g, p = 0.022), but was independent of leukocyte infiltration defined by flow cytometry. Stroke size correlated with severity of cardiac dysfunction (r = 0.590, p = 0.008). Statistical parametric mapping identified a direct association between neuroinflammation at 7 days in a cluster of voxels including the insular cortex and reduced ejection fraction (ρ = − 0.396, p = 0.027). Suppression of microglia led to lower TSPO signal at 7 days which correlated with spared late cardiac function after MCAo (r = − 0.759, p = 0.029). Regional neuroinflammation early after cerebral ischemia influences subsequent cardiac dysfunction. Total body TSPO PET enables monitoring of neuroinflammation, providing insights into brain–heart inter-organ communication and may guide therapeutic intervention to spare cardiac function post-stroke.

Neurofilaments in heart failure-depicting the brain-heart axis

Abstract Introduction Experimental studies have fueled theoretical concerns about neurocognitive side effects of the angiotensin-receptor-neprilysin-inhibitor (ARNi) sacubitril/valsartan as neprilysin is not only involved in the degradation of vasoactive peptides, but also in the degradation of amyloid-β in the brain. To date, no study could demonstrate cognition- and dementia-related adverse effects following neprilysin-inhibition. Recent advances in blood-based tests made it feasible to precisely measure the concentration of neurofilament light chain in plasma (sNfL).sNfl has been found to be altered in neurodegenerative disease, making it a potential biomarker for screening and early detection of cognitive impairment. This study investigated the association of sNfL levels with the severity of disease and prognosis in heart failure with reduced ejection fraction (HFrEF) and explored the response of sNfL levels to the initiation of ARNi. Methods HFrEF patients were prospectively enrolled and clinically followed-up.sNfL levels were measured by a single-molecule array assay. The association of sNfL with heart failure (HF) severity and outcome was assessed. The discriminatory power of sNFL was assessed using Harrell's C-statistic and was compared to NT-proBNP. In a subset of 47 patients, sNfL levels were determined before the initiation of ARNi (baseline), 3±2 months (short-term) and 12±3 months (long-term) after. Results A total of 177 HFrEF patients were included into the study. Median age was 61 years (IQR: 51–72) and 75% of patients were male. Median sNfL levels were 26.2 pg/ml (IQR: 14.1–43.8).sNfL concentration was significantly associated with HF severity reflected by NT-proBNP (rs=0.361, p&amp;lt;0.001) and NYHA class (p&amp;lt;0.001) (Figure 1A). Thirty-one (17.5%) patients died during a median follow-up time of 2.8 years (IQR: 2.3–3.3). Increased sNfL concentration was indicative for worse overall survival even after adjustment for age, sex, kidney function and NT-proBNP [adj. HR for ln[sNfL]: 1.78 (95% CI: 1.13–2.80, p=0.012] (Figure 1B). In terms of discriminatory accuracy, sNfl was comparable with NT-proBNP (C-index: 0.75 [CI: 0.67–0.83] vs. 0.71 [CI: 0.63–0.80], p=0.299). Regarding the effect of ARNi-therapy no significant change in sNfL was observed at short- and long-term follow-up (26.0 pg/ml [IQR: 15.1–51.4] vs. 31.5 pg/ml [IQR: 15.8–51.3]; vs. 31.3 pg/ml [IQR: 15.5–54.0], p&amp;gt;0.05 for all) (Figure 2). Conclusions This study suggests that sNFL is a high performing marker to predict outcome in HFrEF independent of NT-proBNP. NEP-inhibition by ARNi does not seem to reasonably influence sNfL levels. The nature of sNfL release is uncertain. As sNfL is assumed to be specific for axonal injury, sNfL increase in HFrEF may be driven by hypoperfusion due to fixed peripheral vasoconstriction characteristic for more severe disease states. Whether sNfL levels are able to aid screening and early therapy of neurocognitive decline in HFrEF has to be elucidated in further studies. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Austrian Society of Cardiology - Research Grant

Hemorrhagic Cerebral Insults and Secondary Takotsubo Syndrome: Findings in a Novel In Vitro Model Using Human Blood Samples.

Intracranial hemorrhage results in devastating forms of cerebral damage. Frequently, these results also present with cardiac dysfunction ranging from ECG changes to Takotsubo syndrome (TTS). This suggests that intracranial bleeding due to subarachnoid hemorrhage (SAH) disrupts the neuro–cardiac axis leading to neurogenic stress cardiomyopathy (NSC) of different degrees. Following this notion, SAH and secondary TTS could be directly linked, thus contributing to poor outcomes. We set out to test if blood circulation is the driver of the brain–heart axis by investigating serum samples of TTS patients. We present a novel in vitro model combining SAH and secondary TTS to mimic the effects of blood or serum, respectively, on blood–brain barrier (BBB) integrity using in vitro monolayers of an established murine model. We consistently demonstrated decreased monolayer integrity and confirmed reduced Claudin-5 and Occludin levels by RT-qPCR and Western blot and morphological reorganization of actin filaments in endothelial cells. Both tight junction proteins show a time-dependent reduction. Our findings highlight a faster and more prominent disintegration of BBB in the presence of TTS and support the importance of the bloodstream as a causal link between intracerebral bleeding and cardiac dysfunction. This may represent potential targets for future therapeutic inventions in SAH and TTS.