Pathophysiology Of Takotsubo Cardiomyopathy Research Articles

Abstract 4137907: Elevated Plasma Neopterin Levels in Patients with Takotsubo Cardiomyopathy

Background: Takotsubo cardiomyopathy (TC) is characterized by left ventricular apical ballooning and intact coronary arteries. The pathogenesis of this disorder is likely to be catecholamine-mediated myocyte damage, microvascular dysfunction and subsequent oxidative stress; however, a number of possible alternative theories have been suggested. Neopterin is produced by activated macrophages following stimulation by interferon-g produced by T-lymphocytes and is capable of enhancing the oxidative potential of reactive oxygen species. The aim of this study was to compare plasma neopterin levels between TC patients and patients with coronary artery disease. Methods: Plasma neopterin levels were measured on admission in patients with TC (n=37), stable angina pectoris (SAP, n=66), unstable angina pectoris (UAP, n=72) and acute myocardial infarction (AMI, n=67) using HPLC. A frozen myocardium specimen was obtained by biopsy from a patient with TC and stained for neopterin, macrophages, and microvessels using immunohistochemistry. Results: Plasma neopterin levels were significantly higher in TC patients compared with SAP patients ( P <0.0001) or UAP patients ( P <0.05), although they were not significantly different from those in AMI patients. In TC patients, plasma neopterin levels correlated positively with neutrophil count (R=0.47, P<0.05) and serum C-reactive protein levels (R=0.38, P<0.05). Immunohistochemical staining showed abundant neopterin-positive macrophages in the myocardium specimen from the patient with TC. Conclusions: This study demonstrates, for the first time, that plasma neopterin levels are elevated in TC patients compared with those in SAP and UAP patients. These findings suggest that neopterin may play an important role in the pathophysiology of Takotsubo cardiomyopathy.

Pulmonary Embolism in Patients Admitted With Takotsubo Cardiomyopathy: Prevalence and Associated In-Hospital Adverse Events.

Introduction Takotsubo cardiomyopathy (TCM) is a poorly understood condition typically characterized by abnormal left ventricular wall motion without causative coronary artery disease and typically presents in post-menopausal women after the experience of a physical or emotional stressor. The pathophysiology of TCM is complex and multifactorial, resulting in complications with varied severity; one of the most concerning complications is thromboembolism, specifically, pulmonary embolism (PE), which is understudied in its relation to TCM.The purpose of this study was to characterize and evaluate the real-world prevalence and outcomes of PE in TCM. Methods Data were derived from the National Inpatient Sample database from January 2016 to December 2019. The primary outcomes assessed were baseline and hospital admission characteristics and comorbidities for patients with TCM with and without PE. Outcomes for TCM patients with PEand predictors of mortality in TCM were also analyzed. Results PE developed in 788 of 40,120 patients with TCM (1.96%). After multivariate adjustment, PE was found to be independently associated with intracardiac thrombus (adjusted odds ratio (aOR) 2.067; 95% confidence interval (CI): 1.198-3.566; p = 0.009) and right heart catheterization (RHC) (aOR: 1.971; 95% CI: 1.160-3.350; p = 0.012). Mortality in patients with TCM was associated with, among other factors, age in years at admission (aOR: 1.104; 95% CI: 1.010-1.017; p = 0.001), African American race (aOR: 1.191; 95% CI: 1.020-1.391; p = 0.027), Asian or Pacific Islander race (aOR: 1.637; 95% CI: 1.283-2.090; p = 0.001), coagulopathy (aOR: 3.393; 95% CI: 2.889-2.986; p = 0.001), liver disease (aOR: 1.446; 95% CI: 1.147-1.824; p = 0.002), atrial fibrillation (aOR: 1.460; 95% CI: 1.320-1.615; p = 0.001), and pulmonary embolism (aOR: 2.217; 95% CI: 1.781-2.760; p = 0.001). Conclusion In a large cohort of patients admitted with TCM,we found the prevalence of PE to be 1.96%. PE, along with comorbidities such as coagulopathy and atrial fibrillation, was found to be a significant predictorof mortality in this patient cohort.

Reverse Takotsubo Stress Cardiomyopathy During Liver Transplantation

Reverse Takotsubo Stress Cardiomyopathy During Liver Transplantation

Pathophysiology of stress cardiomyopathy: A comprehensive literature review.

IntroductionTakotsubo cardiomyopathy is a transient type of acute heart failure with distinct wall motion abnormalities and unclear pathophysiology. This review focuses on the proposed pathophysiological mechanisms that could be involved in the occurrence takotsubo cardiomyopathy.Main bodyAcute stress and subsequent excessive activation of the sympathetic nervous system are major factors in the pathophysiology of takotsubo cardiomyopathy. The high levels of catecholamine work in a triggering manner, generate reactive oxygen species, release inflammatory cytokines, and induce endothelial injury. The incidence of Takotsubo cardiomyopathy has increased following COVID-19 infection and vaccination, which suggests that neurohormonal and psychological factors (i.e., fear and anxiety of infection or vaccination) may have an additional role in the pathophysiology. In addition, inflammatory state, cytokine storm, augmented sympathetic activity, and endothelial dysfunction during the acute phase of COVID-19 infection may participate in Takotsubo cardiomyopathy. Chronic stress is also linked to this complex mechanism by accelerating cripple of endocrinal hypothalamic-pituitary-adrenal axis activity, which influences the cortisol effect on releasing catecholamine, which is directly related to the pathogenesis of takotsubo cardiomyopathy.ConclusionThe excessive activation of the sympathetic nervous system and subsequent high levels of catecholamines could initiate the process. The catecholamines, in turn, generate reactive oxygen species and release inflammatory cytokines (i.e., IL-1, IL-2, IL-6, IL-7, IL-8, CXCL1, TNF-α, and IFN-γ), which causes endothelial injury.

Takotsubo Syndrome

Abstract Takotsubo syndrome occurs in 1-2% of patients admitted in the emergency department with suspicion of ST-segment elevation myocardial infarction (STEMI), over 90% being postmenopause women. Psycho-emotional or physical stress is the main trigger that causes the release of catecholamines, with an important role in the pathophysiology of Takotsubo cardiomyopathy. In most cases, supportive and symptomatic treatment is sufficient, with a dynamic follow-up of the left ventricular (LV) function. Usually, a complete recovery occurs in 3-4 weeks. We are presenting the case of a 67-year-old patient with a severe angina attack which occuredafter a major psycho-emotional stress, with an electrocardiographic appearance of an anterior STEMI and echocardiographic apical ballooning, both compatible with Takotsubo syndrome. Coronary angiography showed a muscle bridge with a systolic compression of 75% on the anterior descending artery (ADA). The evolution was marked by the occurrence of cardiogenic shock remitted under treatment, with complete recovery of LV systolic function. The particularity of the case resides in an acute coronary syndrome (ACS) after a psycho-emotional stress associated with a muscular bridge, as well as the appearance of the cardiogenic shock.

Thyrotoxicosis Induced Takotsubo Cardiomyopathy

Thyrotoxicosis induced Takotsubo cardiomyopathy (TCM) is a rare condition with very few cases in the literature. Although the pathophysiology of TCM has been explored extensively, we do not have a robust understanding of this condition. Thyroid hormone is known to increase myocardial contractility, and while the mechanism is unclear, there is an association between hyperthyroidism and TCM.

Pathophysiology of Takotsubo Cardiomyopathy: Reopened Debate.

Takotsubo cardiomyopathy (TTC), a persistently obscure dysfunctional condition of the left ventricle, is uniquely transient but nevertheless dangerous. It features variable ventricular patterns and is predominant in women. For 30 years, pathophysiologic investigations have progressed only slowly and with inadequate focus. It was initially proposed that sudden-onset spastic obliteration of coronary flow induced myocardial ischemia with residual stunning and thus TTC. Later, it was generally accepted without proof that, in the presence of pain or emotional stress, the dominant mechanism for TTC onset was a catecholamine surge that had a direct, toxic myocardial effect. We think that the manifestations of TTC are more dynamic and complex than can be assumed from catecholamine effects alone. In addition, after reviewing the recent medical literature and considering our own clinical observations, especially on spasm, we theorize that atherosclerotic coronary artery disease modulates and physically opposes obstruction during spasm. This phenomenon may explain the midventricular variant of TTC and the lower incidence of TTC in men. We continue to recommend and perform acetylcholine testing to reproduce TTC and to confirm our theory that coronary spasm is its initial pathophysiologic factor. An improved understanding of TTC is especially important because of the condition's markedly increased incidence during the ongoing COVID-19 pandemic.

Pathogenesis of Ventricular Arrhythmias and Its Effect on Long-Term Prognosis in Patients With Takotsubo Cardiomyopathy.

Takotsubo cardiomyopathy (TTC), also known as broken heart syndrome, stress cardiomyopathy (SCM), or apical ballooning syndrome, is a non-ischemic cardiac disease with an initial clinical presentation that is very similar to acute coronary syndrome (ACS). Ventricular arrhythmias (VAs) contribute significantly to an increase in the rates of death in patients with TTC, especially during the acute phase, in which patients with TTC are more susceptible to develop life-threatening arrhythmias (LTA) such as ventricular tachycardia (VT), ventricular fibrillation (VF), torsades de pointes (TdP), and sudden cardiac death (SCD). However, the pathophysiology of TTC and how VA occurs are still a mystery. We aim to review previous literature and discuss the possible mechanisms of VA in TTC patients.VA usually complicates the acute phase of the disease and worsens the long-term prognosis. Alterations of repolarization (negative T wave, prolonged QTc) indicate a high risk of arrhythmic events (TdP, VT, VF, and SCD). Catecholamine effect on myocardial cells and myocardial edema can create a substrate for the development of VA. Some of the most commonly proposed mechanisms for the development of VA in patients with TTC are coronary vasospasm, myocardial stunning due to catecholamines, re-entry, and triggered activity. Further prospective studies, including a more significant number of patients, are required to understand the disease's pathophysiology better and improve LTA management in patients with TTC.

Biomarkers in patients with Takotsubo cardiomyopathy compared to patients with acute anterior ST-elevation myocardial infarction

Background: Takotsubo cardiomyopathy (TTC) is a syndrome of acute non-coronary heart failure with similar symptoms and electrocardiograms to acute anterior ST-elevation myocardial infarction (STEMI). Little is known about the pathophysiology of TTC. We assessed admission plasma concentrations of biomarkers reflecting neuroendocrine response (copeptin, mid-regional-pro-adrenomedullin, pro-atrial-natriuretic-peptide, soluble thrombomodulin (sTM), syndecan-1) and inflammation (suppression-of-tumorigenicity 2 (ST2), high-sensitive C-reactive-protein) in TTC patients and compared to patients with acute anterior STEMI.Materials and methods: Twenty TTC patients were matched with 40 STEMI patients by age, gender and left ventricular ejection fraction. Blood was sampled upon hospital admission immediately before acute coronary angiography.Results: The groups had similar comorbidities. TTC patients had higher plasma concentrations of sTM: 7.94 (5.89;9.61) vs. 6.42 (5.50;7.82)ng/ml, p = 0.04 and ST2 (53 (32;157) vs. 45 (31;55)ng/ml, p = 0.008) and higher heart rate: 101 (33) vs. 76(14)bpm, p = 0.0001, but lower concentrations of copeptin (10.4 (7.6;39) vs. 92.3 (13;197)pmol/l, p < 0.05) and troponin T (348 (98;759) vs. 1190 (261;4105)ng/l, p = 0.04).Conclusion: TTC patients had higher plasma concentrations of sTM and ST2, higher heart rate and lower copeptin and troponin T concentrations compared to acute anterior STEMI patients. This study contributes to the hypothesis that TTC patients have endothelial cell damage and are hemodynamically more stable than patients with acute anterior STEMI on admission.

Takotsubo Cardiomyopathy: A Brief Review.

Takotsubo cardiomyopathy is a reversible cardiomyopathy with a unique morphological feature of the left ventricle characterized by an apical ballooning appearance known for approximately known 25 years. Catecholamine drive plays an essential role in the pathogenesis and pathophysiology of Takotsubo cardiomyopathy; hence, it is also called stress cardiomyopathy. Physical stress could also have an impact and leads to a greater variety of characteristics in Takotsubo cardiomyopathy.Supportive and symptomatic medication remains the mainstay therapy with priority to improving the function of the left ventricle for several days and full recovery in 3-4 weeks. Due to its similarity with myocardial infarction, Takotsubo cardiomyopathy requires careful diagnosis and management for the best possible outcome.

TAKOSTSUBO CARDIOMYOPATHY AND CARDIOGENIC SHOCK INDUCED BY GI BLEEDING: A CASE REPORT

SESSION TITLE: Monday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Takotsubo Cardiomyopathy (TC), is a syndrome manifested by transient regional systolic dyskinesia of the left ventricle, mimicking myocardial infarction, in the absence of attributable coronary artery disease. Many psychological and physical stresses have been associated with TC, including several gastrointestinal conditions (eg, recurrent vomiting, achalasia, and acute pancreatitis. To the best of our knowledge, there is only one reported case of TC following upper gastrointestinal bleeding (UGIB). We report a second case of stress-induced cardiomyopathy associated with UGIB. CASE PRESENTATION: An 80-year-old lady was admitted to the intensive care unit with UGIB, evident by hematemesis and acute hemoglobin drop. Esophagogastroduodenoscopy revealed 2 peptic ulcers, with no signs of active bleeding and no bleeding stigmata. Colonoscopy showed polyps. She was managed with proton pump inhibitors. Abdomen/Pelvis CT done here showed diverticulitis. The patient remained hemodynamically stable, required no transfusions and hemoglobin remained stable over 3 days from admission. However, the patient developed hemorrhagic shock due to sudden recurrent hematemesis and acute hemoglobin drop to 4.8. She was resuscitated with IVF and transfusion of 4 units of blood. The patient developed chest pain, EKG showed ST elevation in anterolateral leads. Cardiology consulted, left heart catheterization demonstrated tortuous but otherwise normal coronary arteries. Left ventriculogram was typical for catecholamine CM, Transthoracic echo showed an ejection fraction of 20%. She was diagnosed with Takotsubo cardiomyopathy, resulted in a cardiogenic shock. The patient was managed aggressively for cardiogenic shock. However, her condition deteriorated with multiorgan failure and died 24 hours later. DISCUSSION: Takotsubo CM syndrome presents a diagnostic challenge, given the wide spectrum of responsible stressors and the inability to differentiate from acute coronary syndrome without angiography. The exact pathophysiology is not completely understood, but it has been proposed that it is related to transient catecholamine surges, resulting in either multivessel epicardial spasm, microvascular coronary spasm, or possible direct myocardial injury. We hypothesize that our patient had excessive and acute catecholamine release, induced by the stress of acute UGIB and hemorrhagic shock, causing Takotsubo CM. Although most patients with stress cardiomyopathy recover, the risk of severe in-hospital complications is similar to that of acute coronary syndrome. CONCLUSIONS: This case further supports the association between UGIB and Takotsubo CM. It also highlights that stress-induced cardiomyopathy should be suspected in any patient with acute medical illness as there is a direct causal role of catecholamine in the pathophysiology of Takotsubo cardiomyopathy. Reference #1: Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, et al. Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy. The New England journal of medicine. 2015;373(10):929-38. Reference #2: Awais M, Hernandez RA, Bach DS. Takotsubo cardiomyopathy triggered by severe vomiting. The American journal of medicine. 2008;121(12):e3-4. Reference #3: Bibiano Guillén C, García Sanz MT, Serantes Pombo FJ. Vázquez Lima MJ. Transient apical dyskinesia associated with upper digestive tract bleeding. Emergencias. 2008;20:291–296. DISCLOSURES: No relevant relationships by Mohamed Elmassry, source=Web Response No relevant relationships by John Makram, source=Web Response No relevant relationships by Haneen Mallah, source=Web Response No relevant relationships by Rita Medrano Juarez, source=Web Response No relevant relationships by Arunee Motes, source=Web Response No relevant relationships by MENFIL ORELLANA-BARRIOS, source=Web Response No relevant relationships by Pablo Paz, source=Web Response No relevant relationships by Victor Test, source=Web Response

Zumba-induced Takotsubo cardiomyopathy: a case report

BackgroundTakotsubo cardiomyopathy or stress cardiomyopathy is characterized by transient left ventricular apical ballooning in the absence of coronary occlusion. The underlying pathophysiological mechanism is still unclear but possible causes have been proposed mainly catecholamine cardiotoxicity, followed by metabolic disturbance, coronary microvascular impairment, and multivessel epicardial coronary artery vasospasm. Takotsubo cardiomyopathy accounts for 1–2% of patients presenting with acute coronary syndrome with the majority of patients diagnosed with Takotsubo cardiomyopathy being women > 55 years of age. Here, we discuss the case of a 38-year-old woman presenting with typical chest pain, electrocardiography changes and cardiac markers consistent with acute coronary syndrome, who was subsequently diagnosed with Takotsubo cardiomyopathy.Case presentationA 38-year-old healthy American woman with negative past medical history presented to our Emergency Department with chest pain developing while participating in intense outdoor physical activities (Zumba) at a fundraising event. Our patient had typical substernal chest pain induced with exercise and was relieved by sublingual nitroglycerin in the Emergency Department. The pain started after 2 h of intensive Zumba workout. On review of her history, our patient was noted to be taking spironolactone 125 mg once daily for hirsutism for the past year. Our patient denied any family history of cardiac disease or heart failure. She admitted to being a former occasional smoker and to drinking alcohol socially. She denied any illicit drug use. She works as a social worker, and reported that she does not experience much stress in her life and denied any “one big life-changing event” or any major stressful news. While in the Emergency Department, our patient was hemodynamically stable and an electrocardiography was performed and showed sinus rhythm with no ST elevation/depression but noted T-wave inversion in leads I and aVL, and T wave flattening in leads V1 and V2. Her troponin levels were 0.294 and 0.231 consecutively. An echocardiogram was done and showed hypokinetic apical and mid-distal walls and hyperdynamic basal walls of the left ventricle with an ejection fraction of 35–40%, consistent with apical ballooning syndrome. Cardiac catheterization was subsequently done and showed depressed left ventricle systolic function, ejection fraction of 30–35% with anteroapical dyskinesia and no evidence of coronary artery disease.Our patient was diagnosed with Takotsubo cardiomyopathy after fulfilling all four of the Mayo Clinic’s diagnostic criteria and was subsequently treated with a beta blocker, and angiotensin-converting enzyme inhibitor.ConclusionsOur patient did not have one clear trigger for her overt Takotsubo cardiomyopathy other than the Zumba activity. Zumba is considered an activity with excessive sympathetic stimulation leading to catecholamine-induced microvascular spasm or through to direct myocardial toxicity, which is postulated to be behind the pathophysiology of Takotsubo cardiomyopathy. Another interesting finding in our patient was her use of spironolactone, as treatment for hirsutism, which is an aldosterone antagonist. Aldosterone actually potentiates the effects of catecholamine and thus activates the sympathetic system. Spironolactone can thus be considered as cardioprotective against the effects of catecholamine on the heart and that is why it is considered to be beneficial and subsequently improves mortality in chronic heart failure as described in several studies.

Iatrogenic Takotsubo Cardiomyopathy Secondary to Norepinephrine by Continuous Infusion for Shock.

Takotsubo cardiomyopathy is a condition characterized by transient left ventricular systolic and diastolic dysfunction, with a possible direct causal role of catecholamine in its pathophysiology. We present a case of a woman with shock and adrenal insufficiency in whom Takotsubo cardiomyopathy developed after treatment with norepinephrine. This case confirms the direct causal role of catecholamine in the pathophysiology of Takotsubo cardiomyopathy. An 82-year-old woman presented with asthenia, anorexia, nausea and abdominal pain. The patient had been on chronic corticosteroid therapy until 3 months before, when she underwent abdominal surgery and corticosteroids were stopped. She now presented with acute kidney injury, hyponatremia and hyperkalemia and shock. A norepinephrine continuous infusion was administered to maintain a mean arterial pressure over 65 mmHg. An echocardiogram showed severe hypokinesis in the apical segments and hyperdynamic basal segments, with an ejection fraction of 25%. Plasma cortisol level was 4.5 μg/dL (reference range 5–25). Corticosteroid therapy was begun and norepinephrine was tapered and stopped. A new echocardiogram showed normalization of cardiac wall motion and an ejection fraction of 70%. This case highlights the importance of the correction of the cause of shock, as well as the risks associated with the use of norepinephrine if hypotension is severe or if it persists despite fluid administration, as usually recommended. It also confirms the direct causal role of catecholamine in the pathophysiology of Takotsubo cardiomyopathy. To the best of our knowledge, this is the first report of stress-induced cardiomyopathy secondary to norepinephrine by continuous infusion for shock.LEARNING POINTSTakotsubo cardiomyopathy is a condition characterized by transient left ventricular dysfunction of the apex and midventricle in the absence of attributable coronary artery disease.In patients with shock and adrenal insufficiency, who can be erroneously interpreted as septic shock, Takotsubo cardiomyopathy can develop after treatment with norepinephrine.In the management of shock, there are risks associated with recommending the use of norepinephrine if hypotension is severe or if it persists despite fluid administration, when the cause of shock is other than septic shock and is not corrected.There is a direct causal role of catecholamine in the pathophysiology of Takotsubo cardiomyopathy.

Abstract 209: Association Between Cannabis Use and TakoTsubo Cardiomyopathy (TTC): Analysis from the NIS 2012 - 2014

Background and Objective: Marijuana use causes catecholamine surge with consequent tachycardia and elevation of both systolic and diastolic blood pressure. It is unclear if the catecholamine surge associated is sufficient to cause left ventricular wall apical ballooning (TakoTsubo Cardiomyopathy (TTC)). Given the similarity in the pathophysiology of TTC and mechanism of action of cannabis, we sought to investigate if there is any association. Methods: We obtained data from the HCUP-NIS of all patients older than 45 years hospitalized between 2012 - 2014. Our main outcome was diagnosis of TTC, and main exposure variables was cannabis use both identified using the ICD-9 codes. Using the SURVEYLOGISTICS procedure, we performed logistic regressions to estimate the odds of TTC diagnosis and in-hospital mortality among cannabis users adjusting for demographics, comorbidities, and other recreational drugs. Results: Of the 7,805,400 hospitalized patients who were &gt; 45 years, 10,160 (0.1%) had a diagnosis of TTC, 54,311 (0.7%) were nondependent cannabis user and 5,045 (0.1%) were dependent cannabis users. We observed a significant association between TTC and nondependent cannabis use (OR 1.35, 95% CI: 1.10-1.65), but the association was nonsignificant for dependent cannabis use. After adjusting for potential confounders such as age, race, gender, comorbidities, cocaine, amphetamine and alcohol, nondependent cannabis use was associated with a 2-fold increased odds of TTC (AOR 2.00, 95% CI: 1.61-2.40). However, the association remained nonsignificant for dependent cannabis users (AOR 0.70, 95% CI: 0.25-1.92). Also, among patients diagnosed with TTC, there was no significant difference in the odds of in-hospital mortality among cannabis users (dependent and nondependent) when compared to nonusers (AOR 1.04, 95% CI: 0.39 - 2.70). Conclusion: In our study population, nondependent cannabis use was associated with significantly increased odds of TTC. However, among patients with TTC, in-hospital mortality rate was the same irrespective of cannabis exposure.

The Insular Cortex and Takotsubo Cardiomyopathy.

Transient left ventricular dysfunction in patients under emotional stress, also known as Takotsubo cardiomyopathy, has been recognized as a distinct clinical entity. Recent studies have supported the concept notion that the cardiovascular system is regulated by cortical modulation. A network consisting of the insular cortex (Ic), anterior cingulate gyrus, and amygdala plays a crucial role in the regulation of the central autonomic nervous system in relation to emotional stress such as anxiety, fear and sadness. Because the Ic is located in the region of the middle cerebral arteries, its structure tends to be exposed to a higher risk of cerebrovascular disease. Ic damage has been associated with myocardial injury, increased brain natriuretic peptide, and the incidence of Takotsubo cardiomyopathy. Because Ic damage has been associated with increased sympathetic nervous system activity, Ic damage is suggested to have a pivotal role in the pathophysiology of Takotsubo cardiomyopathy. In this review, we focus on the role of the Ic as a mediator for the cardiovascular system in relation to emotional stress, and we summarizes the current knowledge on the relationships between the Ic and Takotsubo cardiomyopathy.

Takotsubo cardiomyopathy triggered by influenza A and complicated with cardiac arrest, a case report

Takotsubo cardiomyopathy is an increasingly recognized cardiac syndrome, characterized by a transient hypokinesis involving left ventricular apical or midventricular segments, and mimicking acute coronary syndrome, in the absence of significant coronary artery stenosis.1,2 The pathophysiology of Takotsubo cardiomyopathy is still unclear, although several mechanisms have been proposed1; moreover, Takotsubo has been related to pulmonary infection3 and influenza virus vaccination.4 Patients with Takotsubo cardiomyopathy have a favorable shortand long-term prognosis compared with those with acute myocardial infarction, secondary to the complete recovery of cardiac function. Nevertheless, cardiac arrest is a rare, but extremely lethal, complication.5

The ATAK complex (Adrenaline, Takotsubo, Anaphylaxis, and Kounis hypersensitivity -associated coronary syndrome) in neurological conditions.

Sir, Takotsubo syndrome, transient left ventricular apical ballooning, takotsubo cardiomyopathy, apical ballooning syndrome, atypical apical ballooning, ampulla cardiomyopathy, broken heart syndrome, transient left ventricular dysfunction syndrome, and stress cardiomyopathy were named after a round-bottomed and narrow-necked fishing pot - takotsubo in Japanese - for trapping octopus because of its resemblance to left ventriculogram. In the interesting report published in Indian Journal of Critical Care Medicine,[1] a 48-year-old man with progressive loss of vision, hypotension, tachycardia, and acidosis was found to have takotsubo syndrome while the coronary arteries were normal. Computerized tomography revealed dense sellar-suprasellar mass lesion extending into the hypothalamus resembling pituitary adenoma with hypocortisolism suggesting hypopituitarism. With dobutamine, atenolol, and noradrenaline, his condition improved. This case raises some issues concerning neurological conditions, mental stress adrenaline, anaphylaxis, and Kounis syndrome. Mental stress commences with impulses from high brain cortical centers that are relayed through the limbic system to hypothalamus resulting in the release of corticotropin-releasing hormone (main coordinator of the mental stress response) and norepinephrine, serotonin, acetylcholine, proopiomelanocortin, adrenocorticotropic hormone, glucagon, growth hormone, and homocysteine that stimulate sympathetic nervous system. These substances can induce heightened cardiovascular activity, endothelial injury, induction of adhesion molecules on the endothelial cells, to which recruited inflammatory cells adhere and translocate to the arterial wall and finally myocardial damage. An acute phase response is engendered, resulting in production of cytokines interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha, acute phase proteins, macrophage, mast cell, and platelet activation that eventually culminate in the development of Kounis syndrome.[2] Stress-induced cytokine production has been incriminated for multivessel coronary artery spasm at epicardial or microvascular levels that induce takotsubo cardiomyopathy. Inflammatory mediators released during anaphylaxis can induce coronary spasm and takotsubo syndrome and adrenaline given for anaphylaxis might contribute to coronary spasm and transient takotsubo syndrome. Adrenaline and noradrenaline released by the renin-angiotensin-aldosterone system together with histamine stimulate the release of more catecholamines by direct action on the adrenal medullary cells. Administration of catecholamines for hemodynamic support of anaphylactic shock would also increase the plasma catecholamines. Catecholamine increase in patients with angina, renders blood platelets more sensitive and more prone to aggregation and thrombosis. Therefore, measurement of anaphylactic inflammatory mediators including histamine, chymase, leukotrienes, thromboxane, and platelet activating factor or the use of corticosteroids or mast cell stabilizers for prevention and treatment may shed light on etiology and pathophysiology of takotsubo cardiomyopathy. The concurrence of acute coronary syndromes with conditions associated with mast cell activation, involving interrelated and interacting inflammatory cells constitute the Kounis syndrome.[3] Inflammatory cells, such as mast cells, T-cells, and macrophages, activate each other via multidirectional stimuli and release mediators capable to induce coronary events. Experimental findings suggest that cardiac mast cell activation by acute stress may contribute to myocardial ischemia through the release of histamine or proinflammatory mediators.[4] Therefore, takotsubo cardiomyopathy should be always considered in neurological conditions with prolonged addisonian crisis. Furthermore, Adrenaline, takotsubo, Anaphylaxis, and Kounis syndrome (ATAK) seem to constitute a challenging contemporary complex that needs inexorable “attack” to elucidate its etiology, pathophysiology, and treatment.[5] Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest

G-protein-coupled receptor kinase 5 polymorphism and Takotsubo cardiomyopathy.

Takotsubo cardiomyopathy (TTC) is an increasingly reported clinical syndrome that mimics acute myocardial infarction without obstructive coronary artery disease and is characterized by transient systolic dysfunction of the apical and/or mid-segments of the left ventricle. The syndrome mainly occurs in postmenopausal women with high adrenergic state conditions. Nowadays, the pathophysiology of TTC is not yet known and the possibility of a genetic predisposition is controversial. The purpose of this study was to assess the genetic susceptibility to TTC through analysis of the L41Q polymorphism of the G-protein-coupled receptor kinase 5 (GRK5). In a cohort of 20 patients enrolled in two tertiary Italian centers with diagnosis of TTC, accordingly to the commonly accepted Mayo Clinic criteria and in 22 healthy individuals (control) we have evaluated the polymorphism in GRK5 gene. The TTC patients had a mean age of 65 ± 9 years and 19 of 20 were women. The presence of one or two L41 alleles of GRK5 was significantly more frequent in TTC group than in the control group (40 vs. 8%, P = 0.0372). In our study, we have found a significant difference in the frequency of GRK5 polymorphism between TTC patients and controls, supporting a genetic predisposition to this cardiac syndrome.

Peri-Operative Takotsubo Cardiomyopathy: A Case Series

Takotsubo Cardiomyopathy (TC) is a reversible, stress-induced, non-ischemic cardiomyopathy associated with temporary weakness of the myocardium and midventricular or apical ballooning [11. Emanuele Cecchi, Guido Parodi, Cristina Giglioli, Silvia Passantino, Brunella Bandinelli, et al. (2013) Stress-Induced Hyperviscosity in the Pathophysiology of Takotsubo Cardiomyopathy. The Am J Cardiol: 1523–1529.,22. Sharkey SW, Lips DL, Pink VR, Maron BJ (2013) Daughter-Mother Tako-Tsubo Cardiomyopathy. The Am J Cardiol 137–138.]. Angina, ST abnormalities, elevated troponins, ventricular asynergy, CHF, and decreased EF are all components of TC. The unique finding is that they occur on the absence of CAD [33. Bielecka-Dabrowa A, Mikhailidis DP, Hannam S, Rysz J, Michalska M, et al. Takotsubo cardiomyopathy -The current state of knowledge. Int J Cardiol:120–125.]. In this case series with IRB approval we report three cases of post-operative cardiac symptoms that all resulted in a diagnosis of TC.

Stress-Induced Hyperviscosity in the Pathophysiology of Takotsubo Cardiomyopathy

Takotsubo cardiomyopathy (TC) is characterized by transient hypokinesis of the left ventricular apex or midventricular segments with coronary arteries without significant stenosis. It is often associated with emotional or physical stress; however, its pathophysiology is still unclear. In the present study, we analyzed the alterations in blood viscosity and markers of endothelial damage induced by sympathetic stimulation in patients with previous TC. Seventeen women (mean age 71 years) with previous TC, included and investigated in the TC Tuscany Registry, were compared to a control group of 8 age- and risk factor-matched women with chest pain and coronary arteries free of stenosis. All subjects underwent the cold pressor test (CPT). Before and after the CPT, the hemorheologic parameters (whole blood viscosity at 0.512 s(-1) and 94.5 s(-1), plasma viscosity, erythrocyte deformability index, and erythrocyte aggregation), catecholamines, plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor levels were assessed. The patients with TC had significantly greater baseline PAI-1 levels (p <0.01) and lower erythrocyte deformability index values (p <0.01). After CPT, both the patients with TC and the controls had a significant increase in several hemorheologic parameters, catecholamines, and von Willebrand factor levels and a decrease in erythrocyte deformability index. However, the PAI-1 levels were significantly increased only in the patients with TC. Compared to the controls, the patients with TC had significantly greater values of whole blood viscosity at 94.5 s(-1) (p <0.05), PAI-1 (p <0.01), von Willebrand factor (p <0.05) and lower erythrocyte deformability index values (p <0.01) after CPT. In conclusion, the results of the present study suggest that in patients with TC, the alterations in erythrocyte membranes and endothelial integrity induced by catecholaminergic storm could determine microvascular hypoperfusion, possibly favoring the occurrence of left ventricular ballooning.