Psychophysiological Stress Reactivity in Monozygotic Twins with and without Takotsubo Syndrome.

OBJECTIVE: Takotsubo syndrome (TTS) is characterized by transient left ventricular dysfunction, often elevated myocardial enzymes, and electrocardiographic changes. Previous studies suggested that an overstimulation of the sympathetic nervous system might cause TTS. However, the pathogenesis of TTS is largely unknown. Therefore, we investigated physiological stress reactivity with a standardized stress test in monozygotic twin sisters, only one of whom had experienced TTS. METHODS: The 60-year-old Caucasian monozygotic twins, one with and one without a previous episode of TTS, were recruited in the Department of Cardiology at the University Hospital Zurich, Switzerland. We applied the Trier Social Stress Test (TSST) to investigate stress reactivity six weeks after the TTS. Hemodynamic measures (heart rate (HR), blood pressure (BP)), heart rate variability (HRV), plasma norepinephrine and epinephrine and salivary cortisol levels were collected immediately before and after the TSST, and 15, 45, and 90 min after TSST. The monozygotic twins differed in their hemodynamic stress response with the TTS twin showing blunted HR and BP reactivity and vagal withdrawal beyond the acute phase of stress. In contrast, the TTS twin showed a higher catecholamine and cortisol stress response with a steady increase in norepinephrine during the recovery period from stress compared to her non-TTS twin sister. CONCLUSION: Large studies applying a case-control design are needed to confirm blunted hemodynamic reactivity, increased catecholamine reactivity, vagal withdrawal, and increased cortisol reactivity to stress in TTS. This may advance the knowledge of psychophysiological mechanisms in TTS.

Assessment of Artificial Intelligence in Echocardiography Diagnostics in Differentiating Takotsubo Syndrome From Myocardial Infarction.

Importance: Machine learning algorithms enable the automatic classification of cardiovascular diseases based on raw cardiac ultrasound imaging data. However, the utility of machine learning in distinguishing between takotsubo syndrome (TTS) and acute myocardial infarction (AMI) has not been studied. Objectives: To assess the utility of machine learning systems for automatic discrimination of TTS and AMI. Design, Settings, and Participants: This cohort study included clinical data and transthoracic echocardiogram results of patients with AMI from the Zurich Acute Coronary Syndrome Registry and patients with TTS obtained from 7 cardiovascular centers in the International Takotsubo Registry. Data from the validation cohort were obtained from April 2011 to February 2017. Data from the training cohort were obtained from March 2017 to May 2019. Data were analyzed from September 2019 to June 2021. Exposure: Transthoracic echocardiograms of 224 patients with TTS and 224 patients with AMI were analyzed. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of the machine learning system evaluated on an independent data set and 4 practicing cardiologists for comparison. Echocardiography videos of 228 patients were used in the development and training of a deep learning model. The performance of the automated echocardiogram video analysis method was evaluated on an independent data set consisting of 220 patients. Data were matched according to age, sex, and ST-segment elevation/non-ST-segment elevation (1 patient with AMI for each patient with TTS). Predictions were compared with echocardiographic-based interpretations from 4 practicing cardiologists in terms of sensitivity, specificity, and AUC calculated from confidence scores concerning their binary diagnosis. Results: In this cohort study, apical 2-chamber and 4-chamber echocardiographic views of 110 patients with TTS (mean [SD] age, 68.4 [12.1] years; 103 [90.4%] were female) and 110 patients with AMI (mean [SD] age, 69.1 [12.2] years; 103 [90.4%] were female) from an independent data set were evaluated. This approach achieved a mean (SD) AUC of 0.79 (0.01) with an overall accuracy of 74.8 (0.7%). In comparison, cardiologists achieved a mean (SD) AUC of 0.71 (0.03) and accuracy of 64.4 (3.5%) on the same data set. In a subanalysis based on 61 patients with apical TTS and 56 patients with AMI due to occlusion of the left anterior descending coronary artery, the model achieved a mean (SD) AUC score of 0.84 (0.01) and an accuracy of 78.6 (1.6%), outperforming the 4 practicing cardiologists (mean [SD] AUC, 0.72 [0.02]) and accuracy of 66.9 (2.8%). Conclusions and Relevance: In this cohort study, a real-time system for fully automated interpretation of echocardiogram videos was established and trained to differentiate TTS from AMI. While this system was more accurate than cardiologists in echocardiography-based disease classification, further studies are warranted for clinical application.

Dynamic Trend of Myocardial Edema in Takotsubo Syndrome: A Serial Cardiac Magnetic Resonance Study.

BACKGROUND: The wall motion abnormalities of the left ventricle (LV) in takotsubo syndrome (TTS) are known to be transient and completely recover within a few weeks. However, there is little information about the relationship between functional recovery and tissue characteristics. The aim of this study was to investigate the recovery process of TTS using cardiovascular magnetic resonance (CMR). METHODS: Consecutive patients with TTS were prospectively enrolled. We performed serial CMR in the acute phase (<72 h after admission), the subacute phase (7-10 days after admission) and the chronic phase (3 months later). To assess the degree of myocardial edema quantitatively, we evaluated the signal intensity of myocardium on T2-weighted images and calculated the signal intensity ratio compared with the skeletal muscle. RESULTS: Fifteen patients with TTS were enrolled. CMR demonstrated reduced LV ejection fraction in the acute phase, and it recovered almost completely by the subacute phase. On the other hand, severe myocardial edema was still observed in the subacute phase, associated with increased LV mass. The highest signal intensity ratio in the subacute phase was correlated with the maximum voltage of negative T wave on electrocardiogram (r = 0.57, p = 0.03). CONCLUSIONS: In patients with TTS, myocardial edema associated with increased LV mass still remained in the subacute phase despite functional recovery of the LV. Electrocardiogram may be useful to assess the degree of myocardial edema in the subacute phase. Our study suggests that myocardial ischemia might have a central role in developing TTS.

[Spontaneous coronary artery dissection]. / Spontane Koronararteriendissektion.

Spontaneous coronary artery dissection Abstract. Spontaneous coronary artery dissection (SCAD) is an increasingly recognized etiology of acute coronary syndrome (ACS) and an important cause of myocardial infarction in women. First described in 1931, SCAD is defined as a spontaneous tear in a coronary artery that is not associated with atherosclerosis, trauma or medical intervention. SCAD predominantly affects younger women, who often lack atherosclerotic risk factors. Some risk factors that have been identified include female sex, pregnancy, severe emotional or physical stress, underlying blood vessel diseases such as fibromuscular dysplasia, and connective tissue diseases such as Ehlers-Danlos syndrome or Marfan syndrome. Previously believed to be rare, a chiefly fatal condition, recent epidemiological data suggests SCAD is accountable for up to 4 % of all ACS cases and up to 35 % of ACS cases in women < 50 years of age. There is a lack of awareness of SCAD among physicians, which probably results in underreporting and underdiagnosing of this disorder. The clinical presentation of SCAD is often similar to that of ACS making differentiation at first presentation difficult. Cardiac enzymes are elevated like in ACS and there are no biomarkers that are specific for the diagnosis of SCAD. Coronary angiography is the gold standard method to distinguish both entities, however correct diagnosis by cath is challenging and SCAD can be truly missed and misdiagnosed as classic ACS. Still there are no randomized controlled trials about the optimal treatment of these patients. But it is suggested that management should be different to atherosclerotic myocardial infarction. Conservative medical treatment is favored in the majority of cases, with percutaneous coronary intervention (PCI) being reserved for high risk patients due to poor interventional outcomes and higher failure rates. However, there is still a lack of data on this poorly understood condition and the optimal management has yet to be determined.

Role of multimodality imaging in evaluation of cardiovascular involvement in COVID-19.

The management of patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be difficult due to the need for dedicated in-hospital pathways, protective measures for healthcare professionals and isolated beds of intensive care, particularly in areas overwhelmed by wide viral spread. Although pneumonia is the most common clinical manifestation in coronavirus disease 2019 (COVID-19), a variety of cardiovascular complications have been reported. An integrated diagnostic algorithm in SARS-CoV-2-infected patients with suspected cardiac involvement (laboratory findings of myocardial injury and electrocardiographic changes) may help to avoid unnecessary examinations and minimize the risk of operator infection. Due to its mobility and bedside feasibility, echocardiography is the first-line imaging technique in this clinical setting. It quickly provides information on ventricular functions, pulmonary hypertension, valve disease and pericardial effusion. In case of ST-segment elevation (STE), urgent coronary angiography should be performed. Cardiac ultrasound helps distinguish between ischemic and non-ischemic myocardial disease and may detect pericardial disease. Transmural ischemic electrocardiographic changes, with or without early elevated troponin levels or echocardiographic wall motion abnormalities, will determine the need for early invasive coronary angiography. Computed tomography (CT) through its multiple applications (chest CT; CT pulmonary angiography and coronary CT angiography; late iodine enhancement CT) and cardiac magnetic resonance might be helpful in reinforcing or redirecting diagnostic hypothesis emerged by other clinical, electrocardiographic and echocardiographic findings. The current pandemic makes it challenging to perform serial invasive and non-invasive diagnostic testing in COVID-19 patients and high serum troponin level. Nevertheless, thoughtful and systematic use of an appropriate multimodality imaging strategy is clinically relevant to detect cardiac injury and distinguish myocardial infarction from, myocarditis, takotsubo syndrome and pulmonary embolism.

Case report of a 66-year-old woman with atypical takotsubo syndrome and concomitant coronary artery disease.

Takotsubo syndrome is increasingly recognised worldwide. As both, takotsubo syndrome and acute myocardial infarction can present with similar findings, including chest pain, elevated troponin and creatine kinase, it is often difficult to differentiate these conditions. Here, we present a challenging case that illustrates (1) difficulties to diagnose takotsubo syndrome in the presence of a significant coronary artery stenosis; (2) how takotsubo syndrome could be misdiagnosed as acute coronary syndrome if diagnostic workup does not include echocardiography or left ventriculography; (3) the importance of cardiac MRI which can contribute to the diagnosis of takotsubo syndrome.

Acute heart and brain failure: a case report.

BACKGROUND: Takotsubo syndrome (TTS) is characterized by often reversible but acute heart failure occurring after an emotional or physical trigger event. The 'brain failure' counterpart is posterior reversible encephalopathy syndrome (PRES) characterized by often reversible but acute neurological symptoms. This case report elaborates on a complex clinical scenario with co-existence of coronary artery disease, TTS and PRES and discusses the pathophysiology, differential diagnosis, and management. CASE SUMMARY: An 82-year-old woman presented with acute heart failure and generalized tonic-clonic seizures following an acute exacerbation of her chronic back pain. Brain magnetic resonance imaging demonstrated vasogenic oedema consistent with the diagnosis of PRES. Focal wall motion abnormalities on echocardiography without causal coronary stenoses on angiography were consistent with the diagnosis of TTS. After an interdisciplinary approach to differential diagnosis and treatment, the patient was discharged to geriatric rehabilitation without heart failure or neurological defects 4 weeks later. DISCUSSION: TTS and PRES share significant similarities in proposed pathogenesis, epidemiology, management, and clinical outcome. This case report highlights the need for early recognition of this rare association and multidisciplinary approach to diagnosis and treatment as both heart and brain disease may require early intervention up to rapid intensive care support.

Takotsubo syndrome: How the broken heart deals with negative emotions.

OBJECTIVES: Patients suffering from Takotsubo syndrome have a higher prevalence of anxiety and depressive disorders compared to those with acute myocardial infarction and might thus show impaired regulation and processing of emotions. METHODS: In this cross-sectional study, neural activity during an emotional picture processing task was examined in 26 Takotsubo patients (on average 27 months after the Takotsubo event) and 22 healthy age- and gender-matched control subjects undergoing functional magnetic resonance imaging. Imaging data were analyzed with two complementary approaches: First, univariate analysis was used to detect brain regions showing condition-specific differences in mean neural activity between groups. Second, multivariate pattern analysis was applied to decode the experimental conditions from individual activity patterns. RESULTS: In the univariate analysis approach, patients showed lower bilateral superior parietal activity during the processing of negative expected pictures compared to the control subjects. The multivariate pattern analysis revealed group differences in decoding negative versus neutral pictures from a widespread network consisting of frontal, parietal, occipital, and cerebellar brain regions. Additionally, differences in decoding the expectation of a negative versus positive upcoming picture were observed in the visual cortex. CONCLUSION: The lower involvement of brain regions observed in Takotsubo patients suggests an impairment in emotion regulation, which might be of etiological importance in this brain-heart disease.

Altered limbic and autonomic processing supports brain-heart axis in Takotsubo syndrome.

AIMS: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction often triggered by emotional or physical stress. Severe activation of the sympathetic nervous system with catecholamine release caused by a dysfunctional limbic system has been proposed as a potential mechanism. We hypothesize that brain regions responsible for autonomic integration and/or limbic processing might be involved in the development of TTS. Here, we investigated alterations in resting state functional connectivity in TTS patients compared with healthy controls. METHODS AND RESULTS: Using brain functional magnetic resonance imaging (fMRI), resting state functional connectivity has been assessed in 15 subjects with TTS and 39 healthy controls. Network-based statistical analyses were conducted to identify subnetworks with altered resting state functional connectivity. Sympathetic and parasympathetic networks have been constructed in addition to the default mode network and whole-brain network. We found parasympathetic- and sympathetic-associated subnetworks both showing reduced resting state functional connectivity in TTS patients compared with controls. Important brain regions constituting parasympathetic- and sympathetic-associated subnetworks included the amygdala, hippocampus, and insula as well as cingulate, parietal, temporal, and cerebellar regions. Additionally, the default mode network as well as limbic regions in the whole-brain analysis demonstrated reduced resting state functional connectivity in TTS, including the hippocampus, parahippocampal, and medial prefrontal regions. CONCLUSION: For the first time, we demonstrate hypoconnectivity of central brain regions associated with autonomic functions and regulation of the limbic system in patients with TTS. These findings suggest that autonomic-limbic integration might play an important role in the pathophysiology and contribute to the understanding of TTS.

International Expert Consensus Document on Takotsubo Syndrome (Part II): Diagnostic Workup, Outcome, and Management.

The clinical expert consensus statement on takotsubo syndrome (TTS) part II focuses on the diagnostic workup, outcome, and management. The recommendations are based on interpretation of the limited clinical trial data currently available and experience of international TTS experts. It summarizes the diagnostic approach, which may facilitate correct and timely diagnosis. Furthermore, the document covers areas where controversies still exist in risk stratification and management of TTS. Based on available data the document provides recommendations on optimal care of such patients for practising physicians.

International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology.

Takotsubo syndrome (TTS) is a poorly recognized heart disease that was initially regarded as a benign condition. Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated. Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS. The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology. This consensus also proposes new diagnostic criteria based on current knowledge to improve diagnostic accuracy.

The challenge of Takotsubo syndrome: heterogeneity of clinical features.

Takotsubo syndrome (TTS) was first described in 1991 as a rare, spontaneous and completely reversible left ventricular regional systolic dysfunction. Today the incidence of TTS is estimated at 2% in patients with an initial diagnosis of acute coronary syndrome (ACS). Notably, the incidence can be as high as 5.9 to 7.5% in female patients. TTS occurs predominantly in postmenopausal women, but both sexes may be affected, at any age. Acute chest pain or dyspnoea is a characteristic symptom of TTS, but initial presentation can also include more severe disease manifestation such as acute heart failure with pulmonary oedema or haemodynamic instability, especially in an in-hospital setting. It is now known that TTS is triggered by not only emotional, but also physical stressors, or a combination of both. Although apical ballooning is the most frequent and typical finding on imaging, different types of TTS have been described, including the midventricular, basal and focal forms. The acute phase of TTS may be complicated by cardiogenic shock, left ventricular outflow tract obstruction, severe mitral valve regurgitation, embolisation of ventricular thrombi and life-threatening ventricular arrhythmias. Furthermore, although originally thought to be a completely reversible condition, the long-term prognosis of TTS is not entirely positive, with a major adverse cardiac and cerebrovascular event (MACCE) rate of 9.9% reported in the InterTAK Registry, the largest series of patients with TTS. The exact aetiology of TTS remains unknown, there are no current treatment guidelines and differential diagnosis from the more frequent ACS entities remains particularly challenging. Overall, TTS remains a poorly understood and under-diagnosed disease, sometimes disguised in clinically atypical presentations. This review presents different TTS cases to illustrate that TTS is a heterogeneous disease.

Takotsubo Syndrome - Predictable from brain imaging data.

Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, with a hospital-mortality rate similar to acute coronary syndrome (ACS). However, the aetiology of TTS is still unknown. In the present study, a multivariate pattern analysis using machine learning with multimodal magnetic resonance imaging (MRI) data of the human brain of TTS patients and age- and gender-matched healthy control subjects was performed. We found consistent structural and functional alterations in TTS patients compared to the control group. In particular, anatomical and neurophysiological measures from brain regions constituting the emotional-autonomic control system contributed to a prediction accuracy of more than 82%. Thus, our findings demonstrate homogeneous neuronal alterations in TTS patients and substantiate the importance of the concept of a brain-heart interaction in TTS.