Twenty-five-year trends in incidence, angiographic appearance, and management of spontaneous coronary artery dissection.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) has been described as an infrequent cause of acute coronary syndrome (ACS). Knowledge about the disease is still limited and SCAD might still be underdiagnosed. OBJECTIVES: Trends in incidence, presentation, angiographic appearance, management, and outcomes of SCAD over 25 years were analyzed. METHODS: Patients with SCAD between 1997 and 2021 at the University Hospital Zurich, Switzerland, were included. Incidences were assessed as total numbers and proportions of ACS cases. Clinical data were collected from medical records and angiographic findings were reviewed. Major adverse cardiac events (MACE) were defined as the composite of all-cause death, cardiac arrest, SCAD recurrence or progression, other myocardial infarction, and stroke. RESULTS: One hundred fifty-six SCAD cases were included in this study. The incidence increased significantly in total (p < 0.001) and relative to ACS cases (p < 0.001). This was based on an increase of shorter lesions (p = 0.004), SCAD type 2 (p < 0.001), and lesions in side branches (p = 0.014), whereas lesions in the left main coronary artery and proximal segments were decreasing (p-values 0.029 and < 0.001, respectively). There was an increase in conservative therapy (p < 0.001). The rate of MACE (24%) was stable, however, there was a reduced proportion of patients with a need for intensive care treatment (p = 0.017). CONCLUSIONS: SCAD represents an important entity of ACS that still might be underappreciated. The increasing incidence of SCAD is likely based on better awareness and familiarity with the disease. A lower need for intensive care treatment suggests positive effects of the increasing implementation of conservative management.

Coronary microvascular dysfunction in Takotsubo syndrome: an analysis using angiography-derived index of microcirculatory resistance.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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: getting closer to its causes.

Takotsubo syndrome (TTS) accounts for between 1 and 4% of cases presenting clinically as an acute coronary syndrome. It typically presents as a transient cardiac phenotype of left ventricular dysfunction with spontaneous recovery. More dramatic presentations may include cardiogenic shock or cardiac arrest. Despite progress in the understanding of the condition since its first description in 1990, considerable questions remain into understanding underlying pathomechanisms. In this review article, we describe the current published data on potential underlying mechanisms associated with the onset of TTS including sympathetic nervous system over-stimulation, structural and functional alterations in the central nervous system, catecholamine secretion, alterations in the balance and distribution of adrenergic receptors, the additive impact of hormones including oestrogen, epicardial coronary or microvascular spasm, endothelial dysfunction, and genetics as potentially contributing to the cascade of events leading to the onset. These pathomechanisms provide suggestions for novel potential therapeutic strategies in patients with TTS including the role of cognitive behavioural therapy, beta-blockers, and endothelin-A antagonists. The underlying mechanism of TTS remains elusive. In reality, physical or emotional stressors likely trigger through the amygdala and hippocampus a central neurohumoral activation with the local and systemic secretion of excess catecholamine and other neurohormones, which exert its effect on the myocardium through a metabolic switch, altered cellular signalling, and endothelial dysfunction. These complex pathways exert a regional activation in the myocardium through the altered distribution of adrenoceptors and density of autonomic innervation as a protective mechanism from myocardial apoptosis. More research is needed to understand how these different complex mechanisms interact with each other to bring on the TTS phenotype.

Clinical characteristics and outcomes of patients with takotsubo syndrome versus spontaneous coronary artery dissection.

BACKGROUND: Takotsubo syndrome (TTS) and spontaneous coronary artery dissection (SCAD) are now increasingly recognized. Both conditions predominantly affect females; however, the exact pathophysiology remains unclear. Large multi-center databases can help elucidate the underlying mechanism and optimize treatments to improve outcomes by allowing us to compare features and outcomes of patients with TTS and patients with SCAD. METHODS: Takotsubo syndrome patients were enrolled from the International Takotsubo Registry and compared to SCAD patients from the Canadian Spontaneous Coronary Artery Dissection Cohort Study. In total 2098 TTS patients and 750 SCAD patients were included in the present study. RESULTS: More than 85% of patients in both groups were females. TTS patients were older compared to SCAD patients. Physical triggers were more common in TTS patients, while emotional triggers and non-identifiable triggering events were more common in SCAD patients. Left ventricular ejection fraction was more impaired in TTS compared to SCAD. TTS patients had more major cardiovascular risk factors, while SCAD patients had a higher rate of migraines and anxiety disorders than TTS patients. Thirty-day mortality was significantly higher in TTS patients, while 30-day stroke rates were comparable between groups. CONCLUSIONS: These findings suggest that women are at higher risk for TTS and SCAD compared to men, which should be considered in the differential diagnosis of those presenting with acute coronary syndrome. Additionally, emotional stressors play a significant role in triggering events particularly in younger women suffering from SCAD. The present findings may help clinicians better differentiate these two entities and aid in the appropriate risk stratification, diagnosis, and management. TRIAL REGISTRATION: ClinicalTrials.gov no. NCT01947621.

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.

Psychosocial and clinical characteristics of a patient with Takotsubo syndrome and her healthy monozygotic twin: a case report.

Background: Takotsubo syndrome (TTS) is an acute heart failure syndrome characterized by transient left ventricular dysfunction, increased myocardial biomarkers, and electrocardiographic changes. Symptoms of TTS are similar to those of acute coronary syndromes, but there is often no significant coronary stenosis. Although emotional and physical stressors are often reported as having triggered TTS, the pathogenesis is largely unknown. To address this issue, we comprehensively characterized a monozygous pair of twin sisters, one of whom experienced TTS. Case summary: The 60-year-old Caucasian monozygotic female twins with and without TTS were examined at the University Hospital Zurich in Switzerland. The twins completed questionnaires and clinical interviews assessing several sociopsychological factors. The twin sister with TTS exhibited higher levels of anxiety, vital exhaustion, social inhibition, and alexithymia, and lower levels of quality of and meaning in life. She was given the diagnoses of social phobia, adjustment disorder, specific anxiety disorder, obsessive-compulsive personality disorder, and an accentuated anxiety-avoidant personality disorder. Additionally, the twin with TTS experienced more-and also more severe-stressors involving life-threatening and dangerous situations over the life course. Discussion: These monozygous female twins with and without TTS differed in several notable aspects of their psychological functioning, psychiatric status, personality, and lifetime stressor exposure. The results thus highlight several factors, besides genetic components, that may play an important role in the pathogenesis of TTS. Looking forward, larger studies using experimental and longitudinal designs are needed to elucidate the role that psychosocial factors play 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.

Pathophysiology of Takotsubo syndrome - a joint scientific statement from the Heart Failure Association Takotsubo Syndrome Study Group and Myocardial Function Working Group of the European Society of Cardiology - Part 2: vascular pathophysiology, gender and sex hormones, genetics, chronic cardiovascular problems and clinical implications.

While the first part of the scientific statement on the pathophysiology of Takotsubo syndrome was focused on catecholamines and the sympathetic nervous system, in the second part we focus on the vascular pathophysiology including coronary and systemic vascular responses, the role of the central and peripheral nervous systems during the acute phase and abnormalities in the subacute phase, the gender differences and integrated effects of sex hormones, genetics of Takotsubo syndrome including insights from microRNA studies and inducible pluripotent stem cell models of Takotsubo syndrome. We then discuss the chronic abnormalities of cardiovascular physiology in survivors, the limitations of current clinical and preclinical studies, the implications of the knowledge of pathophysiology for clinical management and future perspectives and directions of research.

Pathophysiology of Takotsubo syndrome - a joint scientific statement from the Heart Failure Association Takotsubo Syndrome Study Group and Myocardial Function Working Group of the European Society of Cardiology - Part 1: overview and the central role for catecholamines and sympathetic nervous system.

This is the first part of a scientific statement from the Heart Failure Association (HFA) of the European Society of Cardiology focused upon the pathophysiology of Takotsubo syndrome and is complimentary to the previous HFA position statement on Takotsubo syndrome which focused upon clinical management. In part 1 we provide an overview of the pathophysiology of Takotsubo syndrome and fundamental questions to consider. We then review and discuss the central role of catecholamines and the sympathetic nervous system in the pathophysiology, and the direct effects of high surges in catecholamines upon myocardial biology including ß-adrenergic receptor signalling, G-protein coupled receptor kinases, cardiomyocyte calcium physiology, myofilament physiology, cardiomyocyte gene expression, myocardial electrophysiology and arrhythmogenicity, myocardial inflammation, metabolism and energetics. The integrated effects upon ventricular haemodynamics are discussed and integrated into the pathophysiological model.

Spontaneous Coronary Artery Dissection: A Rare Event?

Spontaneous coronary artery dissection is an infrequent cause of acute coronary syndrome with comparable clinical features. Previously considered a rare disease, recent scientific interest has revealed spontaneous coronary artery dissection as an important differential diagnosis of acute coronary syndrome, especially in young women, during pregnancy or postpartum, and in patients with fibromuscular dysplasia or other arteriopathies. However, there remain many uncertainties regarding pathophysiology, risk factors, acute treatment, and optimal long-term management. The aim of this review is to summarize current scientific evidence on epidemiology, management, and outcomes.

Clinical correlates and prognostic impact of neurologic disorders in Takotsubo syndrome.

Cardiac alterations are frequently observed after acute neurological disorders. Takotsubo syndrome (TTS) represents an acute heart failure syndrome and is increasingly recognized as part of the spectrum of cardiac complications observed after neurological disorders. A systematic investigation of TTS patients with neurological disorders has not been conducted yet. The aim of the study was to expand insights regarding neurological disease entities triggering TTS and to investigate the clinical profile and outcomes of TTS patients after primary neurological disorders. The International Takotsubo Registry is an observational multicenter collaborative effort of 45 centers in 14 countries (ClinicalTrials.gov, identifier NCT01947621). All patients in the registry fulfilled International Takotsubo Diagnostic Criteria. For the present study, patients were included if complete information on acute neurological disorders were available. 2402 patients in whom complete information on acute neurological status were available were analyzed. In 161 patients (6.7%) an acute neurological disorder was identified as the preceding triggering factor. The most common neurological disorders were seizures, intracranial hemorrhage, and ischemic stroke. Time from neurological symptoms to TTS diagnosis was ≤ 2 days in 87.3% of cases. TTS patients with neurological disorders were younger, had a lower female predominance, fewer cardiac symptoms, lower left ventricular ejection fraction, and higher levels of cardiac biomarkers. TTS patients with neurological disorders had a 3.2-fold increased odds of in-hospital mortality compared to TTS patients without neurological disorders. In this large-scale study, 1 out of 15 TTS patients had an acute neurological condition as the underlying triggering factor. Our data emphasize that a wide spectrum of neurological diseases ranging from benign to life-threatening encompass TTS. The high rates of adverse events highlight the need for clinical awareness.

Takotsubo Syndrome: Uncovering Myths and Misconceptions.

PURPOSE OF REVIEW: Takotsubo syndrome (TTS) was described in Japan 3 decades ago to affect predominately postmenopausal women after emotional stress. This history is the basis of commonly held beliefs which may contribute to the underdiagnosis and misperception of TTS. RECENT FINDINGS: TTS affects not only women, but can be present in both sexes, and can appear in children as well as in the elderly. TTS is characterized by unique clinical characteristics with morphological variants, and incurs a substantial risk for recurrent events and adverse outcomes. Physical triggers are more common than emotional triggers and are major disease determinants. TTS seems not to be completely transient as patients report ongoing chest pain, dyspnea, or fatigue even after months of the acute event. Knowledge of the clinical features and outcomes of TTS patients has evolved substantially over the past decades. The heterogeneous appearance of TTS needs to be recognized in all medical disciplines to maximize therapy and improve outcomes.

Pathophysiology of Takotsubo Syndrome: JACC State-of-the-Art Review.

Takotsubo syndrome (TTS) has been a recognized clinical entity for 31 years, since its first description in 1990. TTS is now routinely diagnosed in patients who present with acute chest pain, electrocardiographic changes, troponin elevation, unobstructed coronary arteries, and a typical pattern of circumferential left ventricular wall motion abnormalities that usually involve the apical and midventricular myocardium. Increasing understanding of this intriguing syndrome stems from wider recognition, possible increasing frequency, and a rising number of publications focused on the pathophysiology in clinical and laboratory studies. A comprehensive understanding of TTS pathophysiology and evidence-based treatments are lacking, and specific and effective treatments are urgently required. This paper reviews the pathophysiology of this fascinating syndrome; what is known from both clinical and preclinical studies, including review of the evidence for microvascular dysfunction, myocardial beta-adrenergic signaling, inflammation, and electrophysiology; and where focused research needs to fill gaps in understanding 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.

Prognostic value of texture analysis from cardiac magnetic resonance imaging in patients with Takotsubo syndrome: a machine learning based proof-of-principle approach.

Cardiac magnetic resonance (CMR) imaging has become an important technique for non-invasive diagnosis of takotsubo syndrome (TTS). The long-term prognostic value of CMR imaging in TTS has not been fully elucidated yet. This study sought to evaluate the prognostic value of texture analysis (TA) based on CMR images in patients with TTS using machine learning. In this multicenter study (InterTAK Registry), we investigated CMR imaging data of 58 patients (56 women, mean age 68 ± 12 years) with TTS. CMR imaging was performed in the acute to subacute phase (median time after symptom onset 4 days) of TTS. TA of the left ventricle was performed using free-hand regions-of-interest in short axis late gadolinium-enhanced and on T2-weighted (T2w) images. A total of 608 TA features adding the parameters age, gender, and body mass index were included. Dimension reduction was performed removing TA features with poor intra-class correlation coefficients (ICC ≤ 0.6) and those being redundant (correlation matrix with Pearson correlation coefficient r > 0.8). Five common machine-learning classifiers (artificial neural network Multilayer Perceptron, decision tree J48, NaïveBayes, RandomForest, and Sequential Minimal Optimization) with tenfold cross-validation were applied to assess 5-year outcome including major adverse cardiac and cerebrovascular events (MACCE). Dimension reduction yielded 10 TA features carrying prognostic information, which were all based on T2w images. The NaïveBayes machine learning classifier showed overall best performance with a sensitivity of 82.9% (confidence interval (CI) 80-86.2), specificity of 83.7% (CI 75.7-92), and an area-under-the receiver operating characteristics curve of 0.88 (CI 0.83-0.92). This proof-of-principle study is the first to identify unique T2w-derived TA features that predict long-term outcome in patients with TTS. These features might serve as imaging prognostic biomarkers in TTS patients.

Correction to: Multimodality imaging in takotsubo syndrome: a joint consensus document of the European Association of Cardiovascular Imaging (EACVI) and the Japanese Society of Echocardiography (JSE).

In the original publication of the article, the first and the second authors' names should be changed as follows.

Multimodality imaging in takotsubo syndrome: a joint consensus document of the European Association of Cardiovascular Imaging (EACVI) and the Japanese Society of Echocardiography (JSE).

Takotsubo syndrome (TTS) is a complex and still poorly recognized heart disease with a wide spectrum of possible clinical presentations. Despite its reversibility, it is associated with serious adverse in-hospital events and high complication rates during follow-up. Multimodality imaging is helpful for establishing the diagnosis, guiding therapy, and stratifying prognosis of TTS patients in both the acute and post-acute phase. Echocardiography plays a key role, particularly in the acute care setting, allowing for the assessment of left ventricular (LV) systolic and diastolic function and the identification of the typical apical-midventricular ballooning pattern, as well as the circumferential pattern of wall motion abnormalities. It is also useful in the early detection of complications (i.e. LV outflow tract obstruction, mitral regurgitation, right ventricular involvement, LV thrombi, and pericardial effusion) and monitoring of systolic function recovery. Left ventriculography allows the evaluation of LV function and morphology, identifying the typical TTS patterns when echocardiography is not available or wall motion abnormalities cannot be properly assessed with ultrasound. Cardiac magnetic resonance provides a more comprehensive depiction of cardiac morphology and function and tissue characterization and offers additional value to other imaging modalities for differential diagnosis (myocardial infarction and myocarditis). Coronary computed tomography angiography has a substantial role in the diagnostic workup of patients with acute chest pain and a doubtful TTS diagnosis to rule out other medical conditions. It can be considered as a non-invasive appropriate alternative to coronary angiography in several clinical scenarios. Although the role of nuclear imaging in TTS has not yet been well established, the combination of perfusion and metabolic imaging may provide useful information on myocardial function in both the acute and post-acute phase.