Takotsubo syndrome (TTS) is a condition of acute ventricular dysfunction mainly in aging women that is frequently precipitated by episodes of physical or emotional stress. The association with negative emotional triggers such as fear, grief, or interpersonal conflicts was observed soon after the first description of TTS three decades ago and led to the popular term "broken heart syndrome". However, more recent research shows that TTS can also be provoked by pleasant emotions in some patients, referred to as "happy heart syndrome". This review will discuss the role of stressful triggers in patients with TTS and their impact on the course of the disease with a particular focus on characteristic features of happy heart syndrome.

Coronary microvascular dysfunction (CMD) is a prevalent and often underdiagnosed condition with significant implications for adverse cardiovascular outcomes. The pathophysiology of CMD includes structural and functional abnormalities in the coronary microvasculature and epicardial atherosclerosis contributes to downstream reduction in myocardial perfusion and symptoms. Diagnosis relies on advanced invasive or noninvasive imaging techniques, such as PET and cardiac magnetic resonance, capable of quantifying myocardial perfusion and myocardial blood flow reserve. Effective management includes optimizing cardiovascular risk factors and symptom control. Novel therapeutic strategies recently approved for management of diabetes, obesity, and heart failure with preserved ejection fraction offer potentially powerful options for management of CMD.

Takotsubo syndrome (TTS) can be triggered by emotional stress, particularly in postmenopausal women, the primary patient group. However, the psychobiological mechanisms remain elusive. This systematic review aimed to synthesize the literature on peripheral physiological responses to acute psychological stress in TTS patients compared to controls. A meta-analysis was performed when data allowed. The review followed PRISMA guidelines and was registered on PROSPERO (CRD42023393222). PubMed, Embase, APA PsycInfo, Cochrane CENTRAL, ClinicalTrials.gov, and WHO ICTRP were searched from inception to February 2023, with PubMed re-searched in May 2024. Eligible studies involved adult TTS patients, included a control group, used standardized acute psychological stress induction, and measured at least one peripheral physiological marker pre- and post-stress. Risk of bias was assessed with the BIOCROSS tool. Meta-analysis used the R package metafor. Of 5752 records screened, 13 studies (k = 13) comprising 176 TTS patients and 197 controls were included. In the meta-analysis, TTS patients had higher post-stress plasma norepinephrine levels [Hedges' g= 0.50, 95 % CI (0.17, 0.84), p = 0.003, k = 5] and a marginally significant increase in stress-induced norepinephrine [g= 0.28, 95 % CI (-0.05, 0.61), p = 0.09, k = 5] compared to controls without established cardiovascular disease. They showed a smaller left ventricular ejection fraction change [g= -0.44, 95 % CI (-0.87, -0.02), p = .043, k = 3]. The systematic review additionally supported endothelial/vasomotor dysfunction (k = 3), wall motion abnormalities (k = 2), and impaired myocardial perfusion (k = 2) in TTS patients. TTS patients may exhibit distinct physiological responses to psychological stress, particularly in catecholamine levels and cardiac function. Limited studies and unclear bias reduce evidence strength.

Heart failure (HF) is a complex and debilitating syndrome that affects millions of people worldwide. In addition to the syndrome-related functional limitations, such as exercise intolerance and dyspnea, patients frequently suffer from various comorbidities. Neuropsychiatric conditions, including autonomic dysfunction, cognitive impairment, and depression, are important albeit underrecognized comorbidities in HF. Autonomic dysfunction, which is expressed as sympathetic predominance and decreased parasympathetic tone, is a key contributor to HF progression. Depression and cognitive impairment are highly prevalent in HF patients, affecting adherence to medical treatment and increasing morbidity and mortality risk. Stress cardiomyopathy, a usually reversible form of left ventricular dysfunction triggered by emotional or physical stress, is another clinical manifestation of the interplay between the heart and the brain. Early recognition and management of these comorbidities in HF patients are crucial for improving outcomes. This narrative review provides an overview of the pathophysiological mechanisms linking HF and brain disorders and discusses clinical perspectives of heart-brain interactions in the context of HF.

Stroke induces cardiac dysfunction, which increases poststroke mortality and morbidity. An imbalance in the autonomic nervous system resulting from brain injury may serve as the underlying mechanism. The present study investigated whether transcutaneous auricular vagus nerve stimulation (taVNS) attenuates poststroke cardiac dysfunction by activating the parasympathetic nervous system. Adult male mice were subjected to transient middle cerebral artery occlusion (MCAO) and reperfusion surgery. The mice in the treatment group received repeated taVNS starting 60 min after the onset of cerebral ischemia. To assess whether the effects of taVNS were associated with parasympathetic activity, the MCAO mice in the atropine group received intraperitoneal injections of atropine to inhibit parasympathetic activity prior to taVNS. taVNS significantly increased the left ventricular ejection fraction (EF), attenuated myocardial apoptosis, reduced myocardial hypertrophy, and reduced fibrosis following stroke. The beneficial effects of taVNS on cardiac dysfunction were abolished by atropine administration. Heart rate variability (HRV) analysis and western blot analysis revealed that taVNS increased parasympathetic activity but decreased sympathetic dominance in mice with MCAO. Furthermore, the cardioprotective effects of taVNS were associated with muscarinic acetylcholine receptor activation, PI3K-Akt pathway modulation, and eNOS regulation in the heart. Therefore, taVNS alleviates cardiac dysfunction after stroke and is associated with activation of the parasympathetic nervous system.

Negative emotions can have a significant impact on individuals, which then influences their cardiovascular system. However, the underlying pathophysiological mechanisms and clinical implications of this association remain inadequately defined. A narrative review of pertinent literature was conducted to examine the pathophysiology, clinical manifestations, and treatment related to the interplay between emotions and conditions such as takotsubo cardiomyopathy, atherosclerosis, acute plaque rupture, and cardiac arrhythmias. Negative emotions can instigate a chronic stress response, which in turn heightens sympathetic nervous system activity and increases vulnerability to cardiovascular diseases. This intricate relationship between emotional states and cardiovascular health underscores the necessity for targeted lifestyle interventions and clinical strategies aimed at mitigating the adverse effects of negative emotions.

William Bayliss and Ernest Starling are not only famous as pioneers in cardiovascular physiology, but also responsible for the discovery of the first hormone (from the Greek 'excite or arouse'), the intestinal signalling molecule and neuropeptide secretin in 1902. Our research group focuses on neuropeptides and neuromodulators that influence cardiovascular autonomic control as potential biomarkers in disease and tractable targets for therapeutic intervention. Acute myocardial infarction (AMI) and chronic heart failure (CHF) result in high levels of cardiac sympathetic stimulation, which is a poor prognostic indicator. Although beta-blockers improve mortality in these conditions by preventing the action of the neurotransmitter noradrenaline, a substantial residual risk remains. Recently, we have identified the sympathetic co-transmitter neuropeptide-Y (NPY) as being released during AMI, leading to larger infarcts and life-threatening arrhythmia in both animal models and patients. Here, we discuss recently published data demonstrating that peripheral venous NPY levels are associated with heart failure hospitalisation and mortality after AMI, and all cause cardiovascular mortality in CHF, even when adjusting for known risk factors (including brain natriuretic peptide). We have investigated the mechanistic basis for these observations in human and rat stellate ganglia and cardiac tissue, manipulating NPY neurochemistry at the same time as using state-of-the-art imaging techniques, to establish the receptor pathways responsible for NPY signalling. We propose NPY as a new mechanistic biomarker in AMI and CHF patients and aim to determine whether specific NPY receptor blockers can prevent arrhythmia and attenuate the development of heart failure.

The Tpeak-Tend interval on electrocardiogram may be a predictor of worse outcomes in Takotsubo syndrome (TTS), but the mechanisms have not been fully determined. This study aimed to investigate the relationships between the corrected Tpeak-Tend (cTp-e) interval and coronary microvascular-dysfunction (CMD) assessed by the angiography-derived index of microvascular resistance (Angio-IMR) and the in-hospital prognosis in patients with TTS.

We retrospectively evaluated 111 consecutive patients admitted for TTS who underwent coronary angiography at Kindai University Hospital from October 2009 to July 2023. The Tpeak-Tend interval was defined as the time interval between the peak and the end of the T wave in electrocardiogram lead V5 on admission. Angio-IMR was assessed from aortic pressure, quantitative flow ratio (QFR), vessel length and hyperemic velocity using the formula described in validation studies. QFR, vessel length and hyperemic velocity was derived from coronary angiography and QAngio XA 3D software package. The degree of CMD was assessed by the maximum Angio-IMR value in each of the three coronary arteries. The primary endpoint was the relationship between the grade of a prolonged cTp-e interval on admission and Angio-IMR. The secondary endpoint was the relationship between the grade of a prolonged cTp-e interval on admission and in-hospital adverse cardiovascular events (composite of acute heart failure, cardiogenic shock, life-threatening arrhythmia, thrombotic events, stroke and all-cause death). The median age was 77.5 [71.0-83.0] years, and most patients were women (82.0%). The median cTp-e interval was 114.5 [91.2-147.0] ms. The patients were categorized according to the tertiles of the cTp-e interval (T1: 52.4-96.9 ms; T2: 100.1-129.1 ms; T3: 131.7-309.8 ms). There was a stepwise increment in the values of maximum Angio-IMR in each of the three coronary arteries in tertiles of the cTp-e interval (T1 vs. T2 vs. T3: 16.1 [14.7-19.3] vs. 21.8 [16.0-31.1] vs. 29.0 [27.2-31.9], P < 0.001). In-hospital adverse cardiovascular events occurred in 53 of 111 patients (47.7%). There was a stepwise increment in the incidence of in-hospital adverse cardiovascular events in tertiles of the cTp-e interval (T1 vs. T2 vs. T3: 27.1% vs. 54.1% vs. 62.2%, P = 0.007). The multivariable analysis showed that prolonged cTp-e interval (OR: 1.30; 95% CI: 1.12-1.56; P < 0.001) was independent predictors of in-hospital adverse cardiovascular events.

The Tpeak-Tend interval on admission reflected CMD and predicts in-hospital adverse cardiovascular events in patients with TTS.

Takotsubo syndrome or broken-heart syndrome is a rare form of nonischemic cardiomyopathy characterized by regional systolic dysfunction of the left ventricle without evidence of coronary artery disease or acute plaque rupture. This transient impairment in myocardial contractility leads to symptoms and signs that can mimic a myocardial infarction. We present a case of Takotsubo syndrome in a 47-year-old premenopausal woman with complex congenital heart disease who initially presented with acute onset of shortness of breath and chest tightness after a verbal altercation. Extremely rare cases of Takotsubo syndrome have been described in the congenital heart disease population in premenopausal women. This case emphasizes the need to highlight acquired cardiac disease in patients with adult congenital heart disease as this cohort continues to age.

Over the last 20 years, the scientific progresses in molecular biology and genetics in combination with the increasing use in the clinical setting of contrast-enhanced cardiac magnetic resonance (CMR) for morpho-functional imaging and structural myocardial tissue characterization have provided important new insights into our understanding of the distinctive aspects of cardiomyopathy, regarding both the genetic and biologic background and the clinical phenotypic features. This has led to the need of an appropriate revision and upgrading of current nosographic framework and pathobiological categorization of heart muscle disorders. This article proposes a new definition and classification of cardiomyopathies that rely on the combination of the distinctive pathobiological basis (genetics, molecular biology and pathology) and the clinical phenotypic pattern (morpho-functional and structural features), leading to the proposal of three different disease categories, each of either genetic or non-genetic etiology and characterized by a combined designation based on both "anatomic" and "functional" features, i.e., hypertrophic/restrictive (H/RC), dilated/hypokinetic (D/HC) and scarring/arrhythmogenic cardiomyopathy (S/AC). The clinical application of the newly proposed classification approach in the real-world practice appears crucial to design a targeted clinical management and evaluation of outcomes of affected patients. Although current treatment of cardiomyopathies is largely palliative and based on drugs, catheter ablation, device or surgical interventions aimed to prevent and manage heart failure and malignant arrhythmias, better knowledge of basic mechanisms involved in the onset and progression of pathobiologically different heart muscle diseases may allow to the development of disease-specific curative therapy.

In patients with ischemic heart disease, coronary microvascular dysfunction is associated with cardiovascular risk factors and poor prognosis; however, data from healthy individuals are scarce.

The purpose of this study was to assess the impact of cardiovascular risk factors and subclinical atherosclerosis on coronary microvascular function in middle-aged asymptomatic individuals.

Myocardial perfusion was measured at rest and under stress using cardiac magnetic resonance in 453 individuals and used to generate myocardial blood flow (MBF) maps and calculate myocardial perfusion reserve (MPR). Subclinical atherosclerosis was assessed using 3-dimensional vascular ultrasound of the carotid and femoral arteries and coronary artery calcium scoring at baseline and at 3-year follow-up.

Median participant age was 52.6 years (range: 48.9-55.8 years), and 84.5% were male. After adjusting for age and sex, rest MBF was directly associated with the number of the metabolic syndrome components present (elevated waist circumference, systolic and diastolic blood pressure, fasting glucose, and triglycerides and low high-density lipoprotein cholesterol), insulin resistance (homeostatic model assessment for insulin resistance), and presence of diabetes. MPR was reduced in the presence of several metabolic syndrome components, elevated homeostatic model assessment for insulin resistance, and diabetes. Stress MBF was inversely associated with coronary artery calcium presence and with global plaque burden. Higher stress MBF and MPR were associated with less atherosclerosis progression (increase in plaque volume) at 3 years.

In asymptomatic middle-aged individuals free of known cardiovascular disease, the presence of cardiometabolic risk factors and systemic (poly-vascular) subclinical atherosclerosis are associated with impaired coronary microvascular function. Better coronary microvascular function reduces atherosclerosis progression at follow-up. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).

Takotsubo cardiomyopathy (TC), also known as stress-induced cardiomyopathy or "broken heart syndrome," is a transient cardiac syndrome characterized by acute left ventricular dysfunction, often mimicking acute coronary syndrome (ACS). TC is triggered by emotional or physical stress and presents with chest pain, electrocardiographic abnormalities, and elevated cardiac biomarkers, though typically without significant coronary artery obstruction. This case discussed a 66-year-old postmenopausal female who presented with progressive chest discomfort, borderline ST-segment elevation on an electrocardiogram, and mildly elevated cardiac biomarkers, initially raising suspicion for ACS. Urgent cardiac catheterization revealed mild coronary artery disease without significant obstruction, while left ventriculography showed hallmark apical ballooning and preserved basal contractility consistent with TC. Further evaluation revealed an ejection fraction of 24% and grade 2 diastolic dysfunction. Management included guideline-directed medical therapy for heart failure, anticoagulation for thrombus prevention, and comprehensive lifestyle modifications. This case underscores the diagnostic challenges in distinguishing TC from ACS and highlights the critical role of invasive coronary angiography and advanced imaging. The patient's presentation was consistent with TC, yet no single acute emotional or physical stressor was identified, suggesting a multifactorial etiology, potentially influenced by chronic hypertension and nicotine use. Postmenopausal women remain at high risk, likely due to hormonal changes affecting myocardial and vascular resilience. Timely recognition and diagnosis of TC are essential to optimize patient outcomes, as management differs significantly from ACS. This case emphasizes the importance of maintaining a high index of suspicion, particularly in postmenopausal women presenting with ACS-like symptoms, and the value of a multidisciplinary approach to treatment and follow-up.

Coronary microvascular dysfunction (CMD) has been proposed as a crucial factor in the pathophysiology of Takotsubo syndrome (TTS). The angiography-derived index of microcirculatory resistance (caIMR) offers an alternative to conventional hyperemic wire-based IMR to assess CMD. We aimed to evaluate CMD's prevalence, transience, and impact on in-hospital outcomes in TTS.

All three coronary arteries of 96 patients with TTS were assessed for their coronary angiography derived Index of microcirculatory Resistance (caIMR) and compared to non-obstructed vessels of matched patients with ST-elevation myocardial infarction. Further, the association between caIMR and the TTS-specific combined in-hospital endpoint of death, cardiac arrest, ventricular arrhythmogenic events and cardiogenic shock was investigated.

Elevated IMR was present in all TTS patients, with significantly elevated caIMR values in all coronary arteries compared to controls. CaIMR did not differ between apical and midventricular TTS types. CaIMR normalized in TTS patients with follow-up angiographies performed at a median of 28 months (median caIMR at event vs follow-up: LAD 34.8 [29.9-41.1] vs 20.3 [16.0-25.3], p < 0.001; LCX: 38.7 [32.9-50.1] vs 23.7 [19.4-30.5], p < 0.001; RCA: 31.7 [25.0-39.1] vs 19.6 [17.1-24.0], p < 0.001). The extent of caIMR elevation significantly correlated with the combined in-hospital endpoint (p = 0.036).

TTS patients had evidence of elevated caIMR in at least one coronary artery with a trend towards higher LAD caIMR in apical type TTS and normalization after recovery. Furthermore, extent of caIMR elevation was associated with increased risk of in-hospital MACE of TTS patients.

Takotsubo syndrome (TTS) is an acute reversible heart dysfunction affecting mostly post-menopausal women, frequently precipitated by a significant stressful event, presenting as an acute coronary syndrome (ACS) in the absence of obstructive coronary artery disease. The pathogenesis is not fully understood, but a close relationship between individual's mind, brain, neuroendocrine system and the heart may be involved in a mind-heart axis. The purpose of this study was to compare the prevalence of psychopathological findings in TTS patients as compared to healthy subjects, patients affected by psychiatric diseases and patients affected by ACS.

This observational study enrolled 40 female subjects divided into 4 subgroups: TTS patients, healthy subjects, psychiatric patients and ACS patients, matched for age. Psychosocial factors and psychopathological dimensions have been evaluated. Patients who signed informed consent were interviewed by the administration of a complex psychometric battery, including Mini International Neuropsychiatric Interview, Hamilton Rating Scale for Depression, State Trait Anxiety Inventory, Form Y.

Comparing the groups, the TTS group showed a statistically significant difference vs. ACS group concerning psychological violence subscale (P=0.049) of the Childhood Trauma Questionnaire, while significant statistical difference emerged in TTS group vs. healthy subjects control group, regarding cyclothymia subscale (P=0.008). Statistically significant differences were documented in TTS group vs. psychiatric cohort in cyclothymia subscale (P=0.012). Moreover, comparison between TTS and ACS group, revealed a statistically significant difference in the sub-scale of self-confidence and management of negative emotions (P=0.0028). One of the most significant features was the evidence of statistically significant differences in TTS vs. ACS group, concerning total and average value of anxiety (P=0.014 and P=0.031 respectively) and in the comparison of TTS group vs. healthy subjects (P=0.005 for the total anxiety value and P=0.021 for the average value). Finally, both depression and mania were statistically significant raised in the TTS group compared to the healthy subjects' group (P=0.00 and P=0.013, respectively).

Psychosocial and psychopathological dimensions of TTS patients have been explored and analyzed in a cohort of TTS patients vs. ACS, healthy subjects and psychiatric patients, showing statistically significant differences among the various groups. Psychopathological symptoms were more frequent in TTS patients, suggesting an evident involvement of mind-heart axis in this disease. Future studies are needed to investigate the cause-effect relationship between psychopathological features and the occurrence of TTS.

A 68-year-old woman, after an Indian cobra (Naja naja) bite, developed anaphylaxis, Takotsubo cardiomyopathy, and Kounis syndrome. She was initially diagnosed with acute coronary syndrome after anaphylaxis due to exposure to cobra venom, indicating Kounis syndrome. The echocardiogram, electrocardiogram, and almost complete reversal of dyskinetic myocardium established Takotsubo cardiomyopathy. Adrenaline, initially given for anaphylaxis, and noradrenaline as an intravenous infusion for hypotension potentially precipitated the ATAK complex. The diagnosis was established by history, low blood pressure, elevated troponin, numerous dyskinetic segments in the echocardiogram, and normal coronary vessels in the angiogram.

Psychological stress contributes to cardiovascular disease (CVD) and sudden cardiac death, yet its molecular basis remains obscure. RNA binding protein RBM24 plays a critical role in cardiac development, rhythm regulation, and cellular stress. Here, we show that psychological stress activates RBM24 S181 phosphorylation through eIF4E2-GSK3β signaling, which causally links psychological stress to CVD by promoting APOE translation (apolipoprotein E). Using an Rbm24 S181A KI mouse model, we show that impaired S181 phosphorylation leads to cardiac contractile dysfunction, atrial fibrillation, dyslipidemia, reduced muscle strength, behavioral abnormalities, and sudden death under acute and chronic psychological stressors. The impaired S181 phosphorylation of RBM24 inhibits cardiac translation, including APOE translation. Notably, cardiomyocyte-specific expression of APOE rescues cardiac electrophysiological abnormalities and contractile dysfunction, through preventing ROS stress and mitochondrial dysfunction. Moreover, RBM24-S181 phosphorylation acts as a serum marker for chronic stress in human. These results provide a functional link between RBM24 phosphorylation, eIF4E-regulated APOE translation, and psychological-stress-induced CVD.

The prevailing hypothesis posits that Takotsubo syndrome (TTS) is caused by massive sympathetic activation, yet supporting evidence remains inconsistent. The objectives of the present study were to determine whether sympathetic activity and reactivity are enhanced in the recovery phase of TTS, and to evaluate the effect of selective β1-receptor blockade on sympathetic reactivity.

We conducted a case-control study that included 18 female patients with TTS and 13 age- and sex-matched controls. Muscle sympathetic nerve activity was measured through microneurography of the peroneal nerve at rest and during the cold pressor test. In the TTS group, recordings were repeated after randomisation to intravenous metoprolol or placebo. In 10 TTS patients, cardiac sympathetic activity was assessed using iodine 123-metaiodobenzylguanidine scintigraphy. Blood samples were collected during hospitalisation.

Microneurography was performed a median of 27.5 days after patient admission. There were no significant differences in burst incidence, burst frequency, burst height or burst area between the TTS patients and the controls at rest, during stress or after administration of intravenous metoprolol. Iodine 123-metaiodobenzylguanidine scintigraphy was performed a median of 12.5 days after admission, revealing decreased early 1.54 ± 0.13 and late 1.40 ± 0.13 heart-to-mediastinum ratios, and an increased washout rate of 41.8 ± 12.1%. Catecholamine metabolites were comparable between the study groups.

General sympathetic hyperactivity or hyperreactivity unlikely contributes to TTS, as catecholamine levels and muscle sympathetic nerve activity at rest and during stress were similar between the TTS patients and the controls. As scintigraphy showed increased cardiac sympathetic activity, a pathological cardiac adrenergic response and vulnerability to sympathetic activation may be crucial for the development of the syndrome.

Takotsubo cardiomyopathy (TCM), also known as stress-induced cardiomyopathy or "broken heart syndrome," is a transient cardiac condition that often mimics acute coronary syndrome (ACS) but lacks obstructive coronary artery disease. TCM primarily affects postmenopausal women and is often precipitated by physical or emotional stress. This report presents a case of TCM in a 65-year-old woman, emphasizing the diagnostic challenges and clinical management required to distinguish TCM from ACS. A 65-year-old woman presented to the emergency department with sudden chest pain and dyspnea following a recent emotional stressor. Her initial evaluation, including an ECG showing ST-segment elevation and mildly elevated troponin, suggested ACS. However, coronary angiography revealed no significant stenosis, and echocardiography demonstrated apical ballooning with preserved basal segment function, confirming a diagnosis of TCM. She was treated supportively with beta-blockers and an ACE inhibitor. Her hospital course was stable, and follow-up echocardiography showed normalization of left ventricular function, consistent with full recovery. This case contributes to the understanding of TCM, emphasizing the need for awareness in clinical practice to promptly diagnose and manage TCM effectively. Enhanced recognition of its triggers, pathophysiology, and diagnostic criteria can improve patient outcomes and reduce the risk of recurrence.

Takotsubo cardiomyopathy (TTC), also known as stress-induced cardiomyopathy, is a rare condition in children that causes acute, severe, but often reversible systolic dysfunction of the left ventricle. Physical trauma is a recognized trigger, although distinguishing TTC from myocardial contusion in pediatric trauma cases can be challenging due to overlapping clinical features. We present the case of a six-year-old boy involved in a high-impact motor vehicle collision. The patient initially presented with multiple traumatic injuries, including fractures of the skull, ribs, and right upper extremity, as well as pulmonary contusions. After initial stabilization in the pediatric intensive care unit (PICU), he developed hemodynamic instability six hours postoperatively, with elevated troponin levels suggesting myocardial contusion. Echocardiography later revealed severe left ventricular dysfunction with apical akinesia and basal hyperkinesis, hallmark findings of TTC. Inotropic support was switched from dobutamine to milrinone to avoid exacerbating catecholamine-induced myocardial stress. Over seven days, the patient's left ventricular function normalized, with an ejection fraction of 55%, and he was discharged on day 15 in stable condition. This case highlights the importance of early recognition of TTC in pediatric trauma patients, where echocardiography and cautious use of inotropic agents can ensure optimal outcomes.

Patent foramen ovale (PFO) may be an underlying factor in the pathogenesis of migraine, vasospastic angina, and Takotsubo cardiomyopathy. This article reviews the role that PFO may play in each of these clinical entities and discusses potential interventions. It also proposes a novel clinical syndrome wherein PFO may be the unifying link among migraine, coronary vasospasm, and Takotsubo cardiomyopathy in predisposed individuals.

ST-elevation myocardial infarction (STEMI) and Takotsubo syndrome (TS) are two distinct cardiac conditions that both result in sudden loss of cardiac dysfunction and that are difficult to distinguish clinically. This study compared plasma protein changes in 24 women with STEMI and 12 women with TS in the acute phase (days 0-3 post symptom onset) and the stabilization phase (days 7, 14, and 30) to examine the molecular differences between these conditions.

Plasma proteins from STEMI and TS patients were extracted during the acute and stabilization phases and analyzed via quantitative proteomics. Differential expression and functional significance were assessed. Data are accessible on ProteomeXchange, ID PXD051367.

During the acute phase, STEMI patients showed higher levels of myocardial inflammation and tissue damage proteins compared to TS patients, along with reduced tissue repair and anti-inflammatory proteins. In the stabilization phase, STEMI patients exhibited ongoing inflammation and disrupted lipid metabolism. Notably, ADIPOQ was consistently downregulated in STEMI patients in both phases. When comparing the acute to the stabilization phase, STEMI patients showed increased inflammatory proteins and decreased structural proteins. Conversely, TS patients showed increased proteins involved in inflammation and the regulatory response to counter excessive inflammation. Consistent protein changes between the acute and stabilization phases in both conditions, such as SAA2, CRP, SAA1, LBP, FGL1, AGT, MAN1A1, APOA4, COMP, and PCOLCE, suggest shared underlying pathophysiological mechanisms.

This study presents protein changes in women with STEMI or TS and identifies ADIPOQ, SAA2, CRP, SAA1, LBP, FGL1, AGT, MAN1A1, APOA4, COMP, and PCOLCE as candidates for further exploration in both therapeutic and diagnostic contexts.

Catecholamine dysregulation is a common feature of multiple acute and chronic cardiac conditions, including heart failure. To investigate the role of altered α-adrenergic stimulation on cardiac function, we developed a short-term exposure model, administering phenylephrine subcutaneously to mice for one week. Compared to vehicle-injected controls, phenylephrine-treated animals exhibited increased ejection fraction, decreased chamber size, diastolic dysfunction and ventricular hypertrophy in the absence of hypertension. Remarkably, these animals developed extensive fibrotic remodeling of the tissue that plateaued at 24 hours and myocyte hypertrophy localized to regions of fibrotic deposition after 3 days of treatment. Transcriptome analyses of purified myocyte and fibroblast populations from these hearts revealed an unexpected role for myocytes in the production of extracellular matrix. Comparison with other models of cardiac stress, including pressure overload hypertrophy and cytokine activation of fibroblasts, identified stimulus-specific transcriptional circuits associated with cardiac pathology. Given the rapid, robust fibrotic response that preceded myocyte hypertrophy, intercellular communication analyses were conducted to investigate fibroblast to myocyte signaling, identifying potential crosstalk between these cells. These studies thoroughly describe and phenotypically characterize a new model of short-term catecholamine stress and provide an atlas of transcriptional remodeling in myocytes and fibroblasts.

Apical ballooning syndrome, commonly known as Takotsubo syndrome, is a distinct cardiomyopathy often resembling acute myocardial infarction in presentation. Takotsubo syndrome patients exhibit varied patterns of left ventricular wall motion abnormalities, most frequently apical dyskinesis with basal hyperkinesis, that are characteristically transient. Although emotional or physical stressors precipitate Takotsubo syndrome in most cases, a significant proportion presents without identifiable triggers, with a pronounced female predominance. Despite recovery of left ventricular function, Takotsubo syndrome may lead to serious complications akin to acute coronary syndromes. The pathophysiology remains incompletely understood, with catecholamine surge implicated in the genesis of myocardial injury, although direct causation remains debated. Diagnosis involves integrating clinical history, imaging modalities like echocardiography, and cardiac MRI. Psychiatric disorders, particularly anxiety and depression, are frequently associated with Takotsubo syndrome, suggesting a role of chronic stress in disease susceptibility. Management includes supportive care, with anticoagulation considered in cases of apical thrombus, alongside close monitoring for complications and recovery of left ventricular function. This article reviews the current understanding, challenges in diagnosis, and management strategies for Takotsubo syndrome.

Takotsubo syndrome (TTS) is a clinical syndrome characterized by a transient left ventricular dysfunction whose diagnosis can be challenging due to its resemblance to acute myocardial infarction (AMI). Despite the growing recognition of TTS, acute complications and long-term mortality rates are comparable to those observed in AMI patients. In this context, a systematic diagnostic approach is imperative for an accurate patient assessment, with due consideration of the distinctive characteristics and optimal timing of each imaging modality. Coronary angiography with ventriculography may be reserved for cases presenting with ST-segment elevation, whereas in all other cases, the use of multimodality noninvasive imaging allows for a comprehensive evaluation of typical diagnostic features and detection of acute complications while also providing prognostic insights. The aim of this review is to evaluate the current research on non-invasive modalities and to propose a diagnostic algorithm that will facilitate the identification and management of TTS.

After an initial Takotsubo syndrome (TTS) event, there is growing recognition of adverse long-term outcomes, including recurrent TTS events. Recurrent events have been incompletely evaluated.

The objective of this study was to characterize recurrent TTS events and evaluate variables associated with recurrence.

We studied 88 consecutive participants in the Cedars-Sinai Smidt Heart Institute Takotsubo Registry, an observational registry collecting retrospective and prospective data in TTS survivors. Detailed medical records are adjudicated. Standardized psychosocial questionnaires are administered remotely.

Of 88 participants with adjudicated TTS, 15 (17%) experienced at least 1 recurrent TTS event (median 3.30 years to first recurrent event, range 0.13-18.56 years). In 9 of these 15 participants, there were different patterns of wall motion abnormalities observed between events. The recurrence-free survival significantly differed based on the pattern of wall motion abnormalities at the index TTS event. Clinical, electrocardiographic, echocardiographic, and invasive data obtained at the index TTS event were similar between participants who went on to have at least 1 recurrent event and those who did not.

Recurrent TTS episodes occurred in a significant proportion of cases, a median of 3.30 years after the index event. The recurrent episodes often had distinct triggers and different wall motion abnormalities compared to the index event. The wall motion pattern at the index event impacted the recurrence-free survival, though confirmatory studies are needed. TTS participants had a high rate of adverse psychosocial stress characteristics based on detailed questionnaires. (The Cedars-Sinai Smidt Heart Institute Takotsubo Registry & Proteomic Study; NCT03910569).

Takotsubo cardiomyopathy is a rare condition that presents a diagnostic challenge due to its close resemblance to acute myocardial ischemia and other cardiac disorders. The excessive production of catecholamines triggers abnormal and severe changes in the myocardium, typically resulting in significant dyskinesia of the left ventricle's apex, reduced ejection fraction, hypotension, and pulmonary edema. Recent reports suggest that potential risk factors may include postmenopausal syndrome and intense, unexpected stress, whether related to life events or medical conditions. Complications such as heart failure, thrombosis, and severe arrhythmias are infrequent and more likely to occur in patients with pre-existing cardiac conditions. We present the case of a 22-year-old woman who developed intraoperative Takotsubo cardiomyopathy during a transsphenoidal resection of a prolactin-secreting pituitary tumor under general anesthesia. Perioperative combination of cabergoline and oxymetazoline induced intraoperative hypertension, pulmonary edema, and Takotsubo stress cardiomyopathy. To our knowledge, this is the first reported case in the literature of intraoperative Takotsubo cardiomyopathy, potentially linked to the specific combination of intraoperative cabergoline and oxymetazoline.

Patients with Takotsubo syndrome displayed endothelial dysfunction, but underlying mechanisms have not been fully clarified. This study aimed to explore molecular signalling responsible for catecholamine excess induced endothelial dysfunction. Human cardiac microvascular endothelial cells were challenged by epinephrine to mimic catecholamine excess. Patch clamp, FACS, ELISA, PCR, and immunostaining were employed for the study. Epinephrine (Epi) enhanced small conductance calcium-activated potassium channel current (ISK1-3) through activating α1 adrenoceptor. Phenylephrine enhanced edothelin-1 (ET-1) and reactive oxygen species (ROS) production, and the effects involved contribution of ISK1-3. H2O2 enhanced ISK1-3 and ET-1 production. Enhancing ISK1-3 caused a hyperpolarization, which increases ROS and ET-1 production. BAPTA partially reduced phenylephrine-induced enhancement of ET-1 and ROS, suggesting that α1 receptor activation can enhance ROS/ET-1 generation in both calcium-dependent and calcium-independent ways. The study demonstrates that high concentration catecholamine can activate SK1-3 channels through α1 receptor-ROS signalling and increase ET-1 production, facilitating vasoconstriction.

Stress cardiomyopathy refers to a syndrome of acute but reversible left ventricular dysfunction, often triggered by emotional or physical stress. Reverse Takotsubo cardiomyopathy is an uncommon variant that occurs in about 5% of cases. Classically, it has been known to be following a catecholamine surge due to physical or emotional stress. This case highlights the importance for physicians to be aware of the possibility of developing stress cardiomyopathy in patients with acute intra-abdominal processes.

Forty-one-year-old Caucasian female with was admitted with an acute small bowel obstruction. After failing conservative management, it was decided to proceed with surgery. After induction with anesthesia but prior to the surgeons first incision, the patient developed a tachyarrhythmia with hemodynamic compromise requiring the surgery to be aborted. That evening, she developed chest pain with concerns for an acute coronary syndrome. She was taken urgently to the for invasive angiography, which demonstrated reverse Takotsubo.

Intra-abdominal processes and intubation have previously been reported be catalyst for this disease process. This patient had multiple stressors including mechanical bowel obstruction and anesthesia after failing conservative management. The diagnosis was confirmed by coronary angiography and left ventriculogram, and followed up with repeat outpatient echocardiography.

A case of small bowel obstruction that developed reverse Takotsubo preceded by sustained ventricular tachycardia after intubation. The patient did well and had complete recovery cardiac function. Risk factors and underlining mechanism for the different variants of stress cardiomyopathy are not well understood, further investigation is warranted.

The pathophysiology of Takotsubo syndrome (TTS) is not completely understood and the role of chronic stress is among the main mechanistic links. The aim of this study was to explore whether accumulating hair cortisol concentration (HCC), a novel biomarker of chronic stress, is associated with the occurrence of TTS.

A consecutive series of 18 TTS patients and 36 age and sex matched healthy controls were included in our analysis. Hair samples were collected from participants'' vertex. The proximal 2.5 cm of hair was cut in equal parts of 0.5 cm, reflecting mean cortisol levels in time intervals of 0-15, 15-30, 30-45, 45-60 and 60-75 days prior to hair collection.

HCC was higher in TTS group compared to controls at any time point and increased over time starting from 75 days prior to the event. The rate of HCC increase was significantly higher in TTS patients versus controls (beta of interaction = 0.48; 95%CI: 0.36-0.60; p < 0.001).

The steadily increasing trend of HCC in TTS patients suggests that the additive effect of multiple stressful events over several weeks prior TTS onset may disrupt cortisol homeostasis and play a role in TTS pathophysiology.

Takotsubo cardiomyopathy (TCM) is a complex disease that resembles the clinical presentation of acute myocardial infarction with non-obstructive coronary arteries. The aetiology remains elusive despite the comprehensive nature of current guidelines meticulously detailing the diagnostic process.

We present the case of a 64-year-old female who presented with a clinical profile consistent with non-ST elevation myocardial infarction, confirmed by elevated cardiac enzyme levels. Echocardiography raised suspicions of TCM. Angiography presented a challenge, revealing a 65% stenosis of the left anterior descending artery (LAD). Based on the collected evidence, we decided to delay and ultimately forgo LAD revascularization while identifying epicardial vasospasm through a provocation test as a possible cause underlying TCM.

Conducting an acetylcholine provocation test, as recommended by the European Society of Cardiology guidelines for patients with ischaemia and no obstructive coronary artery disease unveiled severe diffuse vasospasm affecting both the LAD and circumflex arteries. The intricate interplay of pathophysiological mechanisms and clinical presentations necessitates ongoing exploration to uncover the mysteries and refine our diagnostic and therapeutic strategies.

β-adrenergic receptor (β-AR) overactivation is a major pathological cue associated with cardiac injury and diseases. AMPK (AMP-activated protein kinase), a conserved energy sensor, regulates energy metabolism and is cardioprotective. However, whether AMPK exerts cardioprotective effects via regulating the signaling pathway downstream of β-AR remains unclear.

Using immunoprecipitation, mass spectrometry, site-specific mutation, in vitro kinase assay, and in vivo animal studies, we determined whether AMPK phosphorylates β-arrestin-1 at serine (Ser) 330. Wild-type mice and mice with site-specific mutagenesis (S330A knock-in [KI]/S330D KI) were subcutaneously injected with the β-AR agonist isoproterenol (5 mg/kg) to evaluate the causality between β-adrenergic insult and β-arrestin-1 Ser330 phosphorylation. Cardiac transcriptomics was used to identify changes in gene expression from β-arrestin-1-S330A/S330D mutation and β-adrenergic insult.

Metformin could decrease cAMP/PKA (protein kinase A) signaling induced by isoproterenol. AMPK bound to β-arrestin-1 and phosphorylated Ser330 with the highest phosphorylated mass spectrometry score. AMPK activation promoted β-arrestin-1 Ser330 phosphorylation in vitro and in vivo. Neonatal mouse cardiomyocytes overexpressing β-arrestin-1-S330D (active form) inhibited the β-AR/cAMP/PKA axis by increasing PDE (phosphodiesterase) 4 expression and activity. Cardiac transcriptomics revealed that the differentially expressed genes between isoproterenol-treated S330A KI and S330D KI mice were mainly involved in immune processes and inflammatory response. β-arrestin-1 Ser330 phosphorylation inhibited isoproterenol-induced reactive oxygen species production and NLRP3 (NOD-like receptor protein 3) inflammasome activation in neonatal mouse cardiomyocytes. In S330D KI mice, the β-AR-activated cAMP/PKA pathways were attenuated, leading to repressed inflammasome activation, reduced expression of proinflammatory cytokines, and mitigated macrophage infiltration. Compared with S330A KI mice, S330D KI mice showed diminished cardiac fibrosis and improved cardiac function upon isoproterenol exposure. However, the cardiac protection exerted by AMPK was abolished in S330A KI mice.

AMPK phosphorylation of β-arrestin-1 Ser330 potentiated PDE4 expression and activity, thereby inhibiting β-AR/cAMP/PKA activation. Subsequently, β-arrestin-1 Ser330 phosphorylation blocks β-AR-induced cardiac inflammasome activation and remodeling.

"Cases of SCMR" is a case series on the SCMR website (https://www.scmr.org) for the purpose of education. The cases reflect the clinical presentation and the use of cardiovascular magnetic resonance in the diagnosis and management of cardiovascular disease. The 2023 digital collection of cases is presented in this article.

Takotsubo syndrome (TTS) was first described in postmenopausal women with transient regional wall motion abnormalities. The trigger is usually an emotional or physical stress. The catecholamine hypothesis seems to be the most prevailing. The main difference between TTS and acute coronary syndromes is that there is no obstructive coronary disease to explain the regional abnormalities. In this form, the left ventricle resembles the fishing jar which is used to trap octopus in Japan. However, to date more atypical forms are recognized. Also, the syndrome is not limited to older women. Nowadays, TTS is presented even in pregnancy and postpartum females. Our experience revealed cases of patients during these periods and some of them suffered from reverse Takotsubo. Additionally, the initial diagnosis in some patients was other than TTS. Due to these findings, we suggest that this type of TTS is not very rare but underestimated. For this reason, further studies are needed to support and explain this condition.