Materiały źródłowe

• #1 Pathophysiology of Takotsubo Syndrome | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/183

  Transient left ventricular apical ballooning syndrome, takotsubo cardiomyopathy, takotsubo syndrome, broken heart syndrome, or stress-induced cardiomyopathy are interchangeable terms used to define a syndrome characterized by transient left ventricular systolic and diastolic dysfunction, electrocardiographic features, and increased levels of myocardial enzymes, similar to acute myocardial infarction, but in the absence of obstructive epicardial coronary artery disease. […] The exact cause of takotsubo syndrome is unclear. However, evidence suggests that an adrenergic surge may contribute to myocardial toxicity or disrupt the microvasculature, leading to left ventricle dysfunction. […] The pathophysiology of stress cardiomyopathy is multifactorial, with several mechanisms implicated, including sympathetic system activation, excessive levels of adrenergic hormones, estrogen deficiency, endothelial dysfunction, and microvascular spasms.

• #2 Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9821117/

  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). […] 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 exact pathophysiology underlying TS remains an enigma. […] The last decade has seen explosive progress in our understanding of the disease, which has opened doors to new targeted treatment modalities. A combination of various pathophysiological mechanisms is considered more accurate than any one mechanism alone. […] Despite the ambiguity in the pathogenesis of TS, the current evidence agrees upon the impact of stressors in causing TS. Sudden somatic and/or emotional stress causes a rise in the levels of catecholamine, resulting in transient left ventricular dysfunction.

• #3 Broken heart syndrome – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/broken-heart-syndrome/symptoms-causes/syc-20354617

  Broken heart syndrome is a heart condition that’s often brought on by stressful situations and extreme emotions. […] The exact cause of broken heart syndrome is unclear. It’s thought that a surge of stress hormones, such as adrenaline, might damage the hearts of some people for a short time. […] A temporary squeezing of the large or small arteries of the heart may play a role in the development of broken heart syndrome. […] People who have broken heart syndrome also may have a change in the structure of the heart muscle. […] Heart attack is generally caused by a complete or near-complete blockage of a heart artery. In broken heart syndrome, the heart arteries are not blocked. But blood flow in the arteries of the heart may be reduced.

• #4 Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management

  https://www.mdpi.com/2077-0383/12/1/125

  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). […] 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 exact pathophysiology underlying TS remains an enigma. […] The last decade has seen explosive progress in our understanding of the disease, which has opened doors to new targeted treatment modalities. […] A combination of various pathophysiological mechanisms is considered more accurate than any one mechanism alone. […] The current evidence suggests gender be a non-modifiable risk factor for TS.

• #5 Pathophysiology of Takotsubo Syndrome | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/183

  In patients with takotsubo syndrome, supraphysiologic levels of plasma catecholamines and neuropeptides, such as norepinephrine, epinephrine, and dopamine, are elevated to 2- to 3-fold higher than normal levels. […] The catecholamine hypothesis is perhaps the most widely accepted pathophysiologic mechanism in takotsubo syndrome. Catecholamine excess can also result in direct myocardial injury. […] Estrogen deficiency leads to endothelial dysfunction, which is linked to coronary epicardial and microvascular spasm—the 2 mechanisms known to cause takotsubo syndrome. […] Inflammation is believed to play a critical role in the development of takotsubo syndrome.

• #6 Takotsubo (Stress) Cardiomyopathy (Broken Heart Syndrome): Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1513631-overview

  Takotsubo cardiomyopathy, also known as stress cardiomyopathy and „broken heart syndrome,” is a sudden, transient cardiac syndrome that involves dramatic left ventricular apical akinesis and mimics acute coronary syndrome (ACS). […] Although the exact etiology of takotsubo cardiomyopathy remains unknown, the syndrome appears to be triggered by a significant emotional or physical stressor. […] The most commonly discussed possible mechanism for takotsubo cardiomyopathy is stress-induced catecholamine release, with toxicity to and subsequent stunning of the myocardium. […] Endomyocardial biopsy of patients with takotsubo cardiomyopathy demonstrates reversible focal myocytolysis, mononuclear infiltrates, and contraction band necrosis. […] Some authors have proposed a unifying hypothesis stating that in susceptible individuals, notably women, neurohormonal stimulation results in acute myocardial dysfunction, as reflected by the characteristic LV wall-motion abnormality of takotsubo cardiomyopathy.

• #7 Takotsubo (Stress) Cardiomyopathy (Broken Heart Syndrome): Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1513631-overview

  Underlying coronary endothelial dysfunction may also play a role in takotsubo cardiomyopathy, wherein an abnormal tendency toward spasticity in the coronary tree can manifest as angina and as takotsubo cardiomyopathy. […] One theory indicates that „substantially increased coronary spasticity may lead to diffuse, transient spastic obliteration of coronary arteries and to critical ischemia, which can be reproduced by acetylcholine testing early after” an episode of takotsubo cardiomyopathy. […] Studies have found that patients with takotsubo cardiomyopathy have, by a statistically significant margin, higher levels of serum catecholamines (norepinephrine, epinephrine, and dopamine) than do patients with myocardial infarction. […] The apical portions of the LV have the highest concentration of sympathetic innervation found in the heart and may explain why excess catecholamines seem to selectively affect its function.

• #8 Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management

  https://www.mdpi.com/2077-0383/12/1/125

  Despite the ambiguity in the pathogenesis of TS, the current evidence agrees upon the impact of stressors in causing TS. […] Sudden somatic and/or emotional stress causes a rise in the levels of catecholamine, resulting in transient left ventricular dysfunction. […] The major cardiovascular hypotheses explaining the pathophysiology of TS have been categorized into vascular, myocardial, or both. […] The cardiac cause or manifestation is acute left ventricular outflow tract obstruction (LVOTO) and direct catecholamine-mediated myocardial stunning. […] Takotsubo Syndrome is believed to be a consequence of several psychiatric and neurological conditions as it is closely linked with various organs, especially the brain. […] The understanding of the molecular and cellular mechanisms behind Broken Heart Syndrome has evolved predominantly over the past few decades.

• #9 Takotsubo syndrome: unravelling the enigma of the broken heart syndrome?—a narrative review – Salamanca – Cardiovascular Diagnosis and Therapy

  https://cdt.amegroups.org/article/view/119786/html

  The significance of sympathetic hyperactivity is widely recognized. In response to stress, the cognitive centers of the brain activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to an increased release of (nor)epinephrine. […] Elevated levels of norepinephrine have been detected in the coronary sinus of TTS patients, indicating an increased release of myocardial catecholamines. […] An increased sympathetic stimulation and increased tissue catecholamine levels due to impaired reuptake appear to play a critical role in TTS. […] The hypothesis of multivessel coronary spasm, resulting from sympathetic hyperactivity, has been suggested as a potential mechanism in TTS. […] The mechanism of myocardial stunning in TTS has also been suggested to involve angiographically silent plaque rupture, thrombosis, and the consequent transient ischemia followed by swift reperfusion.

• #10 Takotsubo syndrome: the broken-heart syndrome

  https://bjcardio.co.uk/2021/03/takotsubo-syndrome-the-broken-heart-syndrome/

  This pathogenic mechanism involves two phases. Phase 1 involves activation of the hypothalamic-pituitary-adrenal axis, and phase 2 involves myocardial dysfunction induced by sympathetic hyperactivity. […] During the second phase, different mechanisms have been considered to explain the cardiotoxicity of catecholamines producing myocardial dysfunction. Among these, the most prominent are direct catecholamine-mediated myocardial stunning and microvascular spasm. […] The causes of the atypical and different anatomical variants in TTS are unknown. The affected myocardium observed in cases of TTS is accompanied by severe histological abnormalities resulting from the direct toxicity of catecholamines, as well as catecholamine-mediated microcirculatory disturbances followed by ischaemia, however, with potential for rapid functional recovery.

• #11 Pathways Case Record: Triggers and Mechanisms of Takotsubo Syndrome – Mass General Advances in Motion

  https://advances.massgeneral.org/research-and-innovation/case-study.aspx?id=1017

  TTS is a reversible cardiomyopathy typically triggered by severe emotional and/or physical stress and presents with myocardial infarction symptoms but lacks occlusive pathology in the coronary arteries. […] While the underlying pathophysiology of TTS remains poorly understood, several mechanisms have been proposed. The predominant mechanisms proposed include microvascular dysfunction and direct catecholamine toxicity. […] The classic mechanism of action of direct catecholamine toxicity was thought to be overstimulation of cardiac adrenergic receptors leading to calcium overload and subsequent myocyte contractile dysfunction. […] Recent studies have demonstrated that very high concentrations of epinephrine outside the standard range, as seen in TTS, trigger a change in the beta-2 adrenergic receptor activity, resulting in reduced inotropy.

• #12 Identifying and Treating Broken Heart Syndrome | CareerCert

  https://www.careercert.com/articles/other-medical-concerns/broken-heart-syndrome/

  Takotsubo cardiomyopathy, also called stress cardiomyopathy, is commonly referred to as broken heart syndrome. […] While these symptoms physically and physiologically mimic an acute myocardial infarction (AMI), broken heart syndrome does not cause any blockage of the coronary arteries. Instead, it uses adrenaline and other hormones to temporarily stun the heart muscle. The precise way adrenaline affects the heart isnt completely known but it is believed that it constricts the coronary arteries resulting in a temporary restriction of oxygenated blood flow to the myocardium. Adrenaline may also cause the influx of a large amount of calcium into myocardial cells. This binds them and makes them temporarily dysfunctional. This infusion of calcium misshapes myocardial cells and causes hypokinesia and slowed relaxation. So, while a patient with broken heart syndrome can have myocardial weakness, in many cases, the heart recovers completely within a few weeks with no permanent or long-term damage.

• #13 Pathways Case Record: Triggers and Mechanisms of Takotsubo Syndrome – Mass General Advances in Motion

  https://advances.massgeneral.org/research-and-innovation/case-study.aspx?id=1017

  Additionally, since most TTS patients are post-menopausal women, the role of estrogen has been investigated. […] Beta receptors are differentially expressed across the human myocardium, which could lead to regional differences in signaling upon catecholamine stimulation. […] There is a yet-unexplained role for direct nervous system signaling contributing to changes in myocyte function. […] We hypothesized that both the distribution of beta receptors in the myocardium and dysfunction of the intrinsic cardiac nervous system could contribute to TTS susceptibility in our patient and in others like her. […] The underlying mechanisms leading to TTS remain poorly understood.

• #14 Takotsubo syndrome: unravelling the enigma of the broken heart syndrome?—a narrative review – Salamanca – Cardiovascular Diagnosis and Therapy

  https://cdt.amegroups.org/article/view/119786/html

  There has been growing interest in considering the role of coronary microcirculation (resistance vessels) as a pivotal factor in the pathogenesis of TTS. […] The high prevalence of TTS in postmenopausal women strongly suggests a potential hormonal factor at play. […] The brain-heart axis remains a burning topic that requires further exploration and may hide the key to further understand the pathophysiology of TTS. […] The majority of TTS patients have coronary arteries that appear normal or show non-significant coronary artery disease. Consequently, there has been growing interest in considering the role of coronary microcirculation (resistance vessels) as a pivotal factor in the pathogenesis of TTS. […] TTS is distinguished by the presence of increased inflammation in the myocardium due to macrophage infiltration, changes in the distribution of monocyte subsets, and elevated systemic proinflammatory cytokine levels. […] The enduring myocardial abnormalities over time prompt the question of whether these issues predated the initial TTS episode.

• #15 Takotsubo cardiomyopathy – Wikipedia

  https://en.wikipedia.org/wiki/Takotsubo_cardiomyopathy

  It has been suggested that the response to catecholamines (such as epinephrine and norepinephrine, released in response to stress) leads to heart muscle dysfunction that contributes to takotsubo cardiomyopathy. […] The theory of vasospasm is not easily distinguished from microvascular dysfunction, and microvascular dysfunction could explain vasospasticity. […] Impaired microvascular function is seen in a vast majority, if not all, of patients with TTS and is one of the most widely held theories. […] It is likely that there are multiple factors at play that could include some amount of vasospasm and failure of the microvasculature. These factors can overlap and create the complex sequela leading to ischemia and left ventricle contraction abnormality.

• #16 Takotsubo syndrome: the broken-heart syndrome

  https://bjcardio.co.uk/2021/03/takotsubo-syndrome-the-broken-heart-syndrome/

  Since TTS was first described, in addition to spasm of the epicardial coronary arteries, diffuse coronary vasoconstriction was documented and can have a pathogenic role. Some authors consider that severe and prolonged microvascular constriction causes acute transient myocardial ischaemia in patients with TTS, leading to a severe impairment of left ventricle (LV) contractility involving areas of increased wall stress, such as the mid-left ventricular wall and the apex. Therefore, TTS may be considered a novel form of ACS. […] The exact pathophysiology of TTS remains incompletely understood; nonetheless, the hypothesis of involvement of a catecholamine surge is the most accepted, currently, specifically, involving an adrenergic cascade through the hypothalamic-pituitary-adrenal axis.

• #17 Takotsubo syndrome: unravelling the enigma of the broken heart syndrome?—a narrative review – Salamanca – Cardiovascular Diagnosis and Therapy

  https://cdt.amegroups.org/article/view/119786/html

  There has been growing interest in considering the role of coronary microcirculation (resistance vessels) as a pivotal factor in the pathogenesis of TTS. […] The high prevalence of TTS in postmenopausal women strongly suggests a potential hormonal factor at play. […] The brain-heart axis remains a burning topic that requires further exploration and may hide the key to further understand the pathophysiology of TTS. […] The majority of TTS patients have coronary arteries that appear normal or show non-significant coronary artery disease. Consequently, there has been growing interest in considering the role of coronary microcirculation (resistance vessels) as a pivotal factor in the pathogenesis of TTS. […] TTS is distinguished by the presence of increased inflammation in the myocardium due to macrophage infiltration, changes in the distribution of monocyte subsets, and elevated systemic proinflammatory cytokine levels. […] The enduring myocardial abnormalities over time prompt the question of whether these issues predated the initial TTS episode.

• #18 Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management

  https://www.mdpi.com/2077-0383/12/1/125

  The role of the adrenergic system and myocardial survival pathways play a pivotal role in regulating the response of cardiac myocyte to catecholamines in times of stress and exercise. […] Estrogen plays an important role in TS due to its cardioprotective action. […] The pathophysiologic and molecular mechanisms are largely unknown and the limited studies conducted lack significant samples for a conclusive declaration. […] An excess of catecholamines is said to be the possible pathophysiologic phenomenon that contributes to the development of TS. […] Circulating microRNAs have been indicated in the possible pathogenesis of TS by sensitizing the heart to an adrenergic stimulus. […] A catena of studies has shown monocyte and macrophage infiltration of the myocardium in TS. […] Some other molecular mechanisms are also implicated in BHS.

• #19 Acute stress and broken heart syndrome. A case report | Revista Colombiana de Psiquiatría (English Edition)

  https://www.elsevier.es/en-revista-revista-colombiana-psiquiatria-english-edition–479-articulo-acute-stress-broken-heart-syndrome–S2530312017300607

  Oestrogens are a protective factor against cardiovascular disease because they inhibit myofibroblast differentiation, regulate the effect of epinephrine on the cardiac presynaptic nerves, and attenuate catecholamine- and glucocorticoid-mediated stress response. […] Takotsubo cardiomyopathy is more prevalent in postmenopausal women, probably due to oestrogen depletion occurring at this stage. […] Takotsubo cardiomyopathy is a disease triggered by physical or emotional stress, and is characterised by reversible left ventricular dysfunction, and wall motion abnormalities, typically hypokinesia in the apical segment and hyperkinesia in the basal segments that causes the characteristic apical ballooning that extend beyond the territory of a coronary artery.

• #20 Pathogenic Mechanisms of Takotsubo Cardiomyopathy or Broken Heart Syndrome

  https://touroscholar.touro.edu/sjlcas/vol11/iss2/5/

  Takotsubo Cardiomyopathy (TTC) is a temporary heart-wall motion abnormality with the clinical presentation of a myocardial infarction. […] This paper explores the theories of the pathogenesis of TTC including coronary artery spasm, microvascular dysfunction, and catecholamine excess. […] The coronary artery spasm theory involves an occlusion of a blood vessel caused by a sudden vasoconstriction of a coronary artery. […] The microvascular dysfunction theory is challenged in the limited and underdeveloped methods of testing for its presence. […] The theory involving catecholamines is based on the catecholamine surge that many patients experience with emotional or physical stressors. […] Further research focused on this theory discovered the protective nature of estrogen against the catecholamine surge, explaining the prevalence of TTC in post-menopausal women. […] Analysis of the three theories found the catecholamine theory to be the most probable mechanism behind TTC, but further research is necessary to confirm TTC pathogenesis.

• #21 Takotsubo syndrome: the broken-heart syndrome

  https://bjcardio.co.uk/2021/03/takotsubo-syndrome-the-broken-heart-syndrome/

  Takotsubo syndrome (TTS) also known as broken-heart syndrome, Takotsubo cardiomyopathy, and stress-induced cardiomyopathy is a recently discovered acute cardiac disease first described in Japan in 1991. […] The aetiology of TTS is not fully understood, despite intensive research into its possible causes. […] The higher incidence of TTS in postmenopausal women suggests hormonal influences. Reduced oestrogen levels during menopause increase endothelial dysfunction (imbalance between vasoconstricting and vasodilating factors) leading to microvascular coronary artery spasm, one of the pathogenetic mechanisms proposed for TTS. […] The exact pathophysiology of TTS remains incompletely understood. Nevertheless, the hypothesis of the involvement of a catecholamine surge is the most accepted, currently. This involves an adrenergic cascade through the hypothalamic-pituitary-adrenal axis.

• #22 Broken heart syndrome A case study

  https://www.racgp.org.au/afp/2012/january-february/broken-heart-syndrome

  Takotsubo cardiomyopathy was first described by Sato et al in 1990. It is described as a depression of the contractile function of the mid and apical segments of the left ventricle with compensatory hyperkinesis of the basal walls. This leads to ballooning of the ventricular apex with systole. […] The most commonly postulated pathogenesis of takotsubo cardiomyopathy is that an intensely stressful emotional or physical trigger causes an excess of circulating catecholamines, which cause both direct myocardial toxicity and microvascular spam/dysfunction leading to myocardial stunning and consequent contractile dysfunction. The more dense distribution of adrenoceptors at the apex might explain why the apex is usually affected while the base of the ventricle is spared. Oestrogen down regulates cardiac adrenoceptors and attenuates their response to activation, providing a plausible reason why the condition is largely confined to postmenopausal women.

• #23 Takotsubo syndrome: unravelling the enigma of the broken heart syndrome?—a narrative review – Salamanca – Cardiovascular Diagnosis and Therapy

  https://cdt.amegroups.org/article/view/119786/html

  There has been growing interest in considering the role of coronary microcirculation (resistance vessels) as a pivotal factor in the pathogenesis of TTS. […] The high prevalence of TTS in postmenopausal women strongly suggests a potential hormonal factor at play. […] The brain-heart axis remains a burning topic that requires further exploration and may hide the key to further understand the pathophysiology of TTS. […] The majority of TTS patients have coronary arteries that appear normal or show non-significant coronary artery disease. Consequently, there has been growing interest in considering the role of coronary microcirculation (resistance vessels) as a pivotal factor in the pathogenesis of TTS. […] TTS is distinguished by the presence of increased inflammation in the myocardium due to macrophage infiltration, changes in the distribution of monocyte subsets, and elevated systemic proinflammatory cytokine levels. […] The enduring myocardial abnormalities over time prompt the question of whether these issues predated the initial TTS episode.

• #24 Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management

  https://www.mdpi.com/2077-0383/12/1/125

  The role of the adrenergic system and myocardial survival pathways play a pivotal role in regulating the response of cardiac myocyte to catecholamines in times of stress and exercise. […] Estrogen plays an important role in TS due to its cardioprotective action. […] The pathophysiologic and molecular mechanisms are largely unknown and the limited studies conducted lack significant samples for a conclusive declaration. […] An excess of catecholamines is said to be the possible pathophysiologic phenomenon that contributes to the development of TS. […] Circulating microRNAs have been indicated in the possible pathogenesis of TS by sensitizing the heart to an adrenergic stimulus. […] A catena of studies has shown monocyte and macrophage infiltration of the myocardium in TS. […] Some other molecular mechanisms are also implicated in BHS.

• #25 Treatment for broken heart syndrome: can it be healed?

  https://www.pharmaceutical-technology.com/features/treatment-for-broken-heart-syndrome/

  The discovery that it is accompanied by inflammation within the heart and in the rest of the body is an important step forward. […] We now need further research to understand if inflammation causes takotsubo cardiomyopathy and determine if drugs that target inflammation could be the key to fixing broken hearts. […] Researching and then developing treatments for broken heart syndrome is relatively urgent since Aberdeen University researchers have found that patients hearts do not necessarily spontaneously recover with time. […] Further investigation is now required as only by finding out exactly what causes this condition will be able to start thinking about how to treat it so that patients can enjoy better follow-up care.

• #26 Scientists discover possible explanation for broken heart syndrome – BHF

  https://www.bhf.org.uk/what-we-do/news-from-the-bhf/news-archive/2018/december/scientists-discover-possible-explanation-for-broken-heart-syndrome

  BHF-funded researchers have identified the bodys own immune system as a potential key player in the mysterious heart condition, takotsubo cardiomyopathy, commonly known as broken heart syndrome. […] We hypothesized that inflammation is central to the pathophysiology and natural history of broken heart syndrome. […] We found that broken heart syndrome triggers a storm in the immune system which results in acute inflammation in the heart muscle. […] These findings uncover an important and previously unknown mechanism in the pathogenesis of Takotsubo cardiomyopathy, furthermore, whole body as well as myocardial inflammation may serve as a therapeutic target for these patients in the future. […] We now need further research to understand if inflammation causes takotsubo cardiomyopathy and determine if drugs that target inflammation could be the key to fixing broken hearts.

• #27 Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9821117/

  The etiopathogenesis can be explained by cardiovascular and neuropsychiatric mechanisms. […] The major cardiovascular hypotheses explaining the pathophysiology of TS have been categorized into vascular, myocardial, or both. […] The cardiac cause or manifestation is acute left ventricular outflow tract obstruction (LVOTO) and direct catecholamine-mediated myocardial stunning. […] Takotsubo Syndrome is believed to be a consequence of several psychiatric and neurological conditions as it is closely linked with various organs, especially the brain. […] The understanding of the molecular and cellular mechanisms behind Broken Heart Syndrome has evolved predominantly over the past few decades. […] The ARs play a pivotal role in regulating the response of cardiac myocyte to catecholamines in times of stress and exercise.

• #28 ‘Broken heart’ syndrome may originate in the brain

  https://www.escardio.org/The-ESC/Press-Office/Press-releases/Broken-heart-syndrome-may-originate-in-the-brain

  Scientists have shown for the first time that the brain is involved in the development of a heart condition called Takotsubo syndrome (TTS). […] The study is published in the European Heart Journal today (Tuesday) and the researchers say that although, at this stage, they cannot show that the reduced brain functions definitely cause TTS, their findings suggest that these alterations in the central nervous system may be part of the mechanism involved and they are linked with the onset of TTS in response to stressful or emotional triggers. […] For the first time, we have identified a correlation between alterations to the functional activity of specific brain regions and TTS, which strongly supports the idea that the brain is involved in the underlying mechanism of TTS. […] Emotional and physical stress are strongly associated with TTS, and it has been hypothesised that the overstimulation of the autonomic nervous system may lead to TTS events.

• #29 'Broken heart’ syndrome may originate in the brain | ScienceDaily

  https://www.sciencedaily.com/releases/2019/03/190304195238.htm

  Scientists have shown for the first time that the brain is involved in the development of a heart condition called Takotsubo syndrome (TTS). […] The study is published in the European Heart Journal today (Tuesday) and the researchers say that although, at this stage, they cannot show that the reduced brain functions definitely cause TTS, their findings suggest that these alterations in the central nervous system may be part of the mechanism involved and they are linked with the onset of TTS in response to stressful or emotional triggers. […] „For the first time, we have identified a correlation between alterations to the functional activity of specific brain regions and TTS, which strongly supports the idea that the brain is involved in the underlying mechanism of TTS. Emotional and physical stress are strongly associated with TTS, and it has been hypothesised that the overstimulation of the autonomic nervous system may lead to TTS events.”

• #30 ‘Broken heart’ syndrome may originate in the brain

  https://www.escardio.org/The-ESC/Press-Office/Press-releases/Broken-heart-syndrome-may-originate-in-the-brain

  Therefore, this decrease in communication could negatively affect the way patients respond to stress and make them more susceptible to developing TTS, said Professor Templin. […] Our results suggest that additional studies should be conducted to determine whether this is a causal relationship. […] We hope this study offers new starting points for studying TTS in terms of understanding that it much more than broken heart syndrome and clearly involves interactions between the brain and the heart, which are still not fully understood.

• #31 'Broken heart’ syndrome may originate in the brain | ScienceDaily

  https://www.sciencedaily.com/releases/2019/03/190304195238.htm

  „Importantly, the regions we’ve identified as communicating less with one another in TTS patients are the same brain regions that are thought to control our response to stress. Therefore, this decrease in communication could negatively affect the way patients respond to stress and make them more susceptible to developing TTS,” said Professor Templin. […] „Our results suggest that additional studies should be conducted to determine whether this is a causal relationship. We hope this study offers new starting points for studying TTS in terms of understanding that it much more than 'broken heart’ syndrome and clearly involves interactions between the brain and the heart, which are still not fully understood.”

• #32 Brain Stress Linked to Broken Heart Syndrome

  https://www.genengnews.com/news/brain-stress-linked-to-broken-heart-syndrome/

  A new study headed by researchers at Massachusetts General Hospital has linked heightened stress-related activity in the amygdala region of the brain with an increased risk of a rare and sometimes fatal heart condition known as ‘broken heart syndrome,’ or, more correctly, Takotsubo syndrome (TTS). […] The study suggests that the increased stress-associated neurobiological activity in the amygdala, which is present years before TTS occurs, may play an important role in its development and may predict the timing of the syndrome. […] The process by which stress induces TTS is not well understood but may involve a multi-organ mechanism starting with activation of the stress-sensitive tissues of the brain. This brain activity in turn triggers several further events, including release of stress hormones, activation of the sympathetic nervous system and release of inflammatory cells, each of which can contribute to the development of TTS.

• #33 “Broken Heart” and “Broken Brain”: Which Connection? | Papadis | Cardiology Research

  https://cardiologyres.org/index.php/Cardiologyres/article/view/1336/1282

  The interconnections between brain and heart are increasingly recognized. Takotsubo cardiomyopathy, also known as broken heart syndrome, is characterized by a cardiovascular dysfunction provoked by an emotional or stressful situation. […] However, the exact mechanism of both TGA and TTC is still not entirely understood, and thereby also the interconnection between the two pathological entities remains partially obscure. […] The brain can exert control over the heart through different pathways. The neuro-cardiac axis, consisting of the prefrontal cortex, amygdala, insular cortex, the anterior cingulate cortex and the brainstem, is involved in the control of the autonomic nervous system, and different pathological events in these areas such as ischemic insults, epileptic seizures or tumors can elicit cardiac effects. […] Pathological responses in the CNS can elicit, mainly through these mechanisms, abnormal effects in heart function, such as alteration of blood pressure and cardiac rhythm, alteration in the conduction of the electric impulses and (mainly transient) cardiomyopathies.

• #34 Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management

  https://www.mdpi.com/2077-0383/12/1/125

  The role of the adrenergic system and myocardial survival pathways play a pivotal role in regulating the response of cardiac myocyte to catecholamines in times of stress and exercise. […] Estrogen plays an important role in TS due to its cardioprotective action. […] The pathophysiologic and molecular mechanisms are largely unknown and the limited studies conducted lack significant samples for a conclusive declaration. […] An excess of catecholamines is said to be the possible pathophysiologic phenomenon that contributes to the development of TS. […] Circulating microRNAs have been indicated in the possible pathogenesis of TS by sensitizing the heart to an adrenergic stimulus. […] A catena of studies has shown monocyte and macrophage infiltration of the myocardium in TS. […] Some other molecular mechanisms are also implicated in BHS.

• #35 Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9821117/

  Estrogen plays an important role in TS due to its cardioprotective action. […] The pathophysiologic and molecular mechanisms are largely unknown and the limited studies conducted lack significant samples for a conclusive declaration. […] Circulating microRNAs have been indicated in the possible pathogenesis of TS by sensitizing the heart to an adrenergic stimulus. […] A catena of studies has shown monocyte and macrophage infiltration of the myocardium in TS. […] Some other molecular mechanisms are also implicated in BHS. […] The Broken Heart Syndrome is mostly associated with negative emotions and their impacts and thus is proclaimed to be the Broken Heart syndrome. […] The significance of positive emotions in TS is poorly defined. […] The exact etio-pathogenesis for TS is still obscure, but over the years of extensive research, we have made significant leaps and have framed the treatment for the disease.

• #36 Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management

  https://www.mdpi.com/2077-0383/12/1/125

  The role of the adrenergic system and myocardial survival pathways play a pivotal role in regulating the response of cardiac myocyte to catecholamines in times of stress and exercise. […] Estrogen plays an important role in TS due to its cardioprotective action. […] The pathophysiologic and molecular mechanisms are largely unknown and the limited studies conducted lack significant samples for a conclusive declaration. […] An excess of catecholamines is said to be the possible pathophysiologic phenomenon that contributes to the development of TS. […] Circulating microRNAs have been indicated in the possible pathogenesis of TS by sensitizing the heart to an adrenergic stimulus. […] A catena of studies has shown monocyte and macrophage infiltration of the myocardium in TS. […] Some other molecular mechanisms are also implicated in BHS.

• #37 The role of microRNAs in broken heart syndrome

  https://frontlinegenomics.com/the-role-of-micrornas-in-broken-heart-syndrome/

  Scientists from Imperial College London have identified the role of two key microRNAs in the development of broken heart syndrome. […] Researchers do not fully understand what causes Takotsubo syndrome, however sharp rises in adrenaline caused by an acute stress (like bereavement) are known to trigger the loss of movement in part of the heart wall. This then causes the acute heart failure. […] Overall, these findings highlight that miR-16 and miR-26a sensitise the heart to Takotsubo-like changes produced by adrenaline. As these microRNAs have already been linked with anxiety and depression, they could provide a mechanism between long-term stress and the increased likelihood of Takotsubo. […] The authors noted that measuring these microRNAs in recovered patients during subsequent periods of stress could help predict the likelihood of recurrence and enable preventative action. In addition, understanding the basis behind sensitisation could allow experts to design other prophylactic pharmacological therapies. […] We now need further research determine if drugs that block these microRNAs could be the key to avoiding broken hearts.

• #38 Broken Heart Syndrome: How scientists unravelled the cardiac mystery – BBC Science Focus Magazine

  https://www.sciencefocus.com/the-human-body/broken-heart-syndrome

  Broken heart syndrome can be caused by stressful situations and extreme emotions, such as a loved one dying. […] The bizarre motion of the heart alerts them to something very different happening, and the weak contraction of the apex is a real concern. […] We do have a clue, however, that another class of molecule, which controls how genes turn on and off, might play a role in Takotsubo. These are the microRNAs—the orchestral conductors of the body. […] Two microRNAs, it turned out, were clearly raised in the blood of Takotsubo patients but not in the heart attack victims and so were biomarkers for the syndrome. […] It is possible that her complicated life and day-to-day stress had made her susceptible, so that when the adrenaline surge finally came, she was more likely to get Takotsubo. […] Blocking the microRNAs might be a good pretreatment but, first, this kind of drug is only just coming onto the market and second, we would have to give it to many thousands of people just to protect the susceptible ones.

• #39 Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9821117/

  Estrogen plays an important role in TS due to its cardioprotective action. […] The pathophysiologic and molecular mechanisms are largely unknown and the limited studies conducted lack significant samples for a conclusive declaration. […] Circulating microRNAs have been indicated in the possible pathogenesis of TS by sensitizing the heart to an adrenergic stimulus. […] A catena of studies has shown monocyte and macrophage infiltration of the myocardium in TS. […] Some other molecular mechanisms are also implicated in BHS. […] The Broken Heart Syndrome is mostly associated with negative emotions and their impacts and thus is proclaimed to be the Broken Heart syndrome. […] The significance of positive emotions in TS is poorly defined. […] The exact etio-pathogenesis for TS is still obscure, but over the years of extensive research, we have made significant leaps and have framed the treatment for the disease.

• #40 Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management

  https://www.mdpi.com/2077-0383/12/1/125

  The role of the adrenergic system and myocardial survival pathways play a pivotal role in regulating the response of cardiac myocyte to catecholamines in times of stress and exercise. […] Estrogen plays an important role in TS due to its cardioprotective action. […] The pathophysiologic and molecular mechanisms are largely unknown and the limited studies conducted lack significant samples for a conclusive declaration. […] An excess of catecholamines is said to be the possible pathophysiologic phenomenon that contributes to the development of TS. […] Circulating microRNAs have been indicated in the possible pathogenesis of TS by sensitizing the heart to an adrenergic stimulus. […] A catena of studies has shown monocyte and macrophage infiltration of the myocardium in TS. […] Some other molecular mechanisms are also implicated in BHS.

• #41 Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management

  https://www.mdpi.com/2077-0383/12/1/125

  The role of the adrenergic system and myocardial survival pathways play a pivotal role in regulating the response of cardiac myocyte to catecholamines in times of stress and exercise. […] Estrogen plays an important role in TS due to its cardioprotective action. […] The pathophysiologic and molecular mechanisms are largely unknown and the limited studies conducted lack significant samples for a conclusive declaration. […] An excess of catecholamines is said to be the possible pathophysiologic phenomenon that contributes to the development of TS. […] Circulating microRNAs have been indicated in the possible pathogenesis of TS by sensitizing the heart to an adrenergic stimulus. […] A catena of studies has shown monocyte and macrophage infiltration of the myocardium in TS. […] Some other molecular mechanisms are also implicated in BHS.

• #42 “Broken Heart” and “Broken Brain”: Which Connection? | Papadis | Cardiology Research

  https://cardiologyres.org/index.php/Cardiologyres/article/view/1336/1282

  Although a univocal classification of these cardiomyopathies is still not available, two main entities have been described: the neurologic stunned myocardium (NSM) and the TTC. In both, the pathophysiological mechanism resides probably in a catecholamine storm, triggered by an acute neurological injury in NSM (mainly in the caudal ventrolateral medulla, the tractus solitarius, the dorsal motor vagal nucleus and the posterior hypothalamus), by emotional or physical stress with consequent activation of hypotalamo-pituitary-adrenal and sympatho-adrenomedullary axis in TTC. […] Alternative mechanisms have been evoked in order to explain TTC, such as immune-mediated or cytokine-mediated mechanisms and alterations in ion channels. […] In conclusion, a single, common pathological pathway between TTC and TGA is not self-evident. In particular, it is unclear whether there is a common cause (a single factor such as stress that could explain both conditions) or if one condition (such as TGA) could elicit the other (for example TTC). […] However, in order to further elucidate the neuroendocrinological mechanisms in TTC, further studies are warranted. […] Another pathophysiological hypothesis was described from neuroanatomical studies of TTC patients, which showed decreased resting functional connectivity in some areas of parasympathetic and sympathetic networks, hypothesized to play a role in TGA.

• #43 Takotsubo syndrome: unravelling the enigma of the broken heart syndrome?—a narrative review – Salamanca – Cardiovascular Diagnosis and Therapy

  https://cdt.amegroups.org/article/view/119786/html

  Takotsubo syndrome (TTS) is a condition characterized by transient ventricular regional wall motion abnormalities, without causative coronary artery disease, typically triggered by emotional or physical stress. […] The precise pathogenesis and pathophysiology of TTS remain unknown. Additionally, the relationship between the underlying mechanisms and the anatomical manifestations of left ventricular ballooning also remains unsettled. […] The strong connection with episodes of sudden, unexpected, stress, major physical illness, or trauma, has led to the widespread use of terms like stress cardiomyopathy or broken heart syndrome. In fact, the majority of research endeavours have focused on exploring the possible involvement of catecholamine surges in the development of this condition. […] Numerous pathophysiological pathways have been suggested to play a role in the development of TTS, and each of them has been the focus of extensive research efforts.

• #44

  https://www.clinicalcorrelations.org/2024/10/09/mama-can-you-die-from-a-broken-heart-exploring-the-pathogenesis-of-takotsubo-cardiomyopathy/

  The pathogenesis of takotsubo cardiomyopathy remains a topic of ongoing debate and investigation, with several proposed theories as to its underlying mechanisms. […] The most prominent theory implicates an inappropriate surge in catecholamines, particularly norepinephrine and epinephrine, released in response to an overwhelmingly stressful emotional or physical event. […] In addition to catecholamine-induced toxicity, endothelial dysfunction is an emerging potential contributor to the pathogenesis of takotsubo cardiomyopathy. […] Estrogen, a hormone with many proposed cardioprotective effects, has also been implicated as a mediator in takotsubo cardiomyopathy. […] While there is still work to be done, it is clear that the pathogenesis of takotsubo cardiomyopathy revolves around the complex interplay of sympathetic stimulation, endothelial function, hormonal regulation, and other factors yet to be discovered.

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