International Takotsubo Registry Research Articles

Machine learning-based prediction of in-hospital death for patients with takotsubo syndrome: The InterTAK-ML model.

Takotsubo syndrome (TTS) is associated with a substantial rate of adverse events. We sought to design a machine learning (ML)-based model to predict the risk of in-hospital death and to perform a clustering of TTS patients to identify different risk profiles. A ridge logistic regression-based ML model for predicting in-hospital death was developed on 3482 TTS patients from the International Takotsubo (InterTAK) Registry, randomly split in a train and an internal validation cohort (75% and 25% of the sample size, respectively) and evaluated in an external validation cohort (1037 patients). Thirty-one clinically relevant variables were included in the prediction model. Model performance represented the primary endpoint and was assessed according to area under the curve (AUC), sensitivity and specificity. As secondary endpoint, a K-medoids clustering algorithm was designed to stratify patients into phenotypic groups based on the 10 most relevant features emerging from the main model. The overall incidence of in-hospital death was 5.2%. The InterTAK-ML model showed an AUC of 0.89 (0.85-0.92), a sensitivity of 0.85 (0.78-0.95) and a specificity of 0.76 (0.74-0.79) in the internal validation cohort and an AUC of 0.82 (0.73-0.91), a sensitivity of 0.74 (0.61-0.87) and a specificity of 0.79 (0.77-0.81) in the external cohort for in-hospital death prediction. By exploiting the 10 variables showing the highest feature importance, TTS patients were clustered into six groups associated with different risks of in-hospital death (28.8% vs. 15.5% vs. 5.4% vs. 1.0.8% vs. 0.5%) which were consistent also in the external cohort. A ML-based approach for the identification of TTS patients at risk of adverse short-term prognosis is feasible and effective. The InterTAK-ML model showed unprecedented discriminative capability for the prediction of in-hospital death.

Smoking influence in Takotsubo syndrome: insights from an international cohort.

To assess the influence of tobacco on acute and long-term outcomes in Takotsubo syndrome (TTS). Patients with TTS from the international multicenter German Italian Spanish Takotsubo registry (GEIST) were analyzed. Comparisons between groups were performed within the overall cohort, and an adjusted analysis with 1:1 propensity score matching was conducted. Out of 3,152 patients with TTS, 534 (17%) were current smokers. Smoker TTS patients were younger (63 ± 11 vs. 72 ± 11 years, p < 0.001), less frequently women (78% vs. 90%, p < 0.001), and had a lower prevalence of hypertension (59% vs. 69%, p < 0.01) and diabetes mellitus (16% vs. 20%, p = 0.04), but had a higher prevalence of pulmonary (21% vs. 15%, p < 0.01) and/or psychiatric diseases (17% vs. 12%, p < 0.01). On multivariable analysis, age less than 65 years [OR 3.85, 95% CI (2.86-5)], male gender [OR 2.52, 95% CI (1.75-3.64)], history of pulmonary disease [OR 2.56, 95% CI (1.81-3.61)], coronary artery disease [OR 2.35, 95% CI (1.60-3.46)], and non-apical ballooning form [OR 1.47, 95% CI (1.02-2.13)] were associated with smoking status. Propensity score matching (PSM) 1:1 yielded 329 patients from each group. Smokers had a similar rate of in-hospital complications but longer in-hospital stays (10 vs. 9 days, p = 0.01). During long-term follow-up, there were no differences in mortality rates between smokers and non-smokers (5.6% vs. 6.9% yearly in the overall, p = 0.02, and 6.6%, vs. 7.2% yearly in the matched cohort, p = 0.97). Our findings suggest that smoking may influence the clinical presentation and course of TTS with longer in-hospital stays, but does not independently impact mortality.

584 AN UNUSUAL CASE OF A STRESSED HEART

Abstract A 53-year-old woman was admitted to our emergency department complaining severe stabbing and oppressive retrosternal pain radiating posteriorly to left scapulae and left arm The onset was followed by general malaise, nausea, vomiting which she attributed to a period of intense emotional stress. She denied common cardiovascular risk factors, but in 2019 had a suspected acute coronary syndrome with subsequent finding of normal coronary artery at angiography in another institute. Her past medical history included severe asthma on multiple drug therapy with regular follow-up. Physical exam was normal. Electrocardiogram (ECG) showed subtle diphasic-negative T wave in anterior leads with mild ST depression in V4-V5, with patient still symptomatic. Lab examinations showed significantly increased troponins levels (hsTnI 664 ng/L, reference &amp;lt; 34 ng/L) with other lab values within normal range. A transthoracic echocardiogram at the bedside revealed mildly reduced systolic function with hypo-akinesis of the mid-apical anteroseptal and anterior left ventricular myocardial wall. Therefore, acute coronary syndrome was suspected and heparin and aspirin at a loading dose were administered. Still symptomatic, the patient was admitted in the ICU. In the same day a left heart catheterization revealed normal aspect of epicardial coronary arteries and ventriculography showed preserved basal and apical myocardial wall motion but hypo-akinesis of mid-cavitary walls, suggesting a possible mid-ventricular variant of Takotsubo syndrome (Figure 1). The patient was still symptomatic for stabbing chest pain after coronarography. To rule out the suspicion of acute aortic syndrome and pulmonary embolism, she also underwent a contrast-enhanced chest CT scan, that was fortunately normal. During her hospital stay, the patient had no arrhythmic and hemodynamic complications. Peak troponin level was 5027 ng/L. At serial ECGs, she developed diffuse deep T-wave inversion and a mild prolonged QT interval. Echocardiogram was repeated after 4 days showing complete normalization of left ventricular wall motion and restored ejection fraction also. From the traditional “apical ballooning” Takotsubo Syndrome with apical akinesia and basal hypercontractility, different variants have been described. The mid-ventricular variant, seen in our patient was found in only 14.6% of the cases in the International Takotsubo Registry, followed by basal “reverse” and focal variants (2.2% and 1.5%, respectively).

Body weight and mortality in takotsubo syndrome: insights from the International Takotsubo (InterTAK) registry

Abstract Background/Introduction The obesity paradox has been described in different cardiovascular conditions. Data on the association between obesity and outcomes in patients with Takotsubo syndrome (TTS) are lacking. Purpose The aim of this study was to determine the relation of body weight to mortality in TTS patients. Methods Patients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to July 2021 and with available data on BMI were included in the analysis. Patients were stratified according to BMI (underweight, &amp;lt;18.5 kg/m2; normal weight, 18.5–24.9 kg/m2; overweight, 25.0–29.9 kg/m2; obese, 30.0–34.9 kg/m2; and very obese, ≥35.0 kg/m2). The primary endpoint was mortality at 1 year. Results Of the 2'707 patients, 222 (8.2%) were underweight, 1340 (49.5%) of normal weight, 759 (28.0%) overweight, 268 (9.9%) obese, and 118 (4.4%) very obese. Mortality at 1 year as a function of BMI with 95% confidence interval is given in Figure 1. Mortality at 1 year was 11.3%, 6.9%, 5.5%, 4.9%, and 9.3% in underweight, normal weight, overweight, obese, and very obese patients (p=0.02, Figure 2). Being overweight or obese was significantly associated with a lower mortality at 1 year (HR 0.70, 95% CI 0.51–0.96, p=0.03), and associations remained significant after multivariable adjustments (adjusted HR 0.67, 95% CI 0.46–0.97, p=0.03). Associations were observed when including patients without emotional stressors (adjusted HR 0.64, 95% CI 0.43–0.94, p=0.02), but not when including those with emotional stressors (adjusted HR 1.14, 95% CI 0.30–4.27, p=0.85). Conclusion A U-shaped mortality curve across BMI categories was observed in TTS patients, with lowest mortality rates in obese patients. These observations provide first evidence for the existence of the obesity paradox in TTS. Funding Acknowledgement Type of funding sources: Foundation.

Cardiac troponin elevation and mortality in takotsubo syndrome: new insights from the International Takotsubo (InterTAK) registry

Abstract Background/Introduction Cardiac biomarker elevations are frequently observed in Takotsubo syndrome (TTS). The clinical relevance of cardiac troponin (cTn) elevations in TTS patients remains uncertain and threshold values indicating clinically relevant myocardial injury are unknown. Purpose This study sought to investigate the role of cTn elevations in mortality prediction of patients with TTS. Methods A total of 2,938 patients enrolled in the prospective International Takotsubo (InterTAK) Registry from January 2011 to February 2020 and with available data on baseline and peak cTn levels were included in the analysis. The threshold at which myocardial injury drives mortality was identified using restricted cubic spline analysis. Results Out of 2,938 patients, 222 (7.6%) patients died during 1-year follow-up. A more than 28.8-fold increase of cTn above the upper reference limit was identified as threshold for clinically relevant myocardial injury. Mortality at 1 year was significantly higher in patients with clinically relevant myocardial injury than in those without (Log Rank p&amp;lt;0.001, Figure 1). The presence of clinically relevant myocardial injury was significantly associated with an increased risk of mortality at 5 years (adjusted HR 1.58, 95% CI 1.18–2.12, p=0.002). Clinically relevant myocardial injury was related to 5-year mortality in patients with apical TTS (adjusted HR 1.57, 95% CI 1.21–2.03, p=0.001), with presence of physical stressors (adjusted HR 1.60, 95% CI 1.22–2.11, p=0.001), and with absence of emotional stressors (adjusted HR 1.49, 95% CI, 1.17–1.89, p=0.001). Conclusions This study for the first time determined a troponin threshold for the identification of TTS patients at excess risk of mortality. These findings advance risk stratification in TTS and assist in identifying patients in need for close monitoring and follow-up. Funding Acknowledgement Type of funding sources: Foundation.

64-Year-Old Woman With Aphasia and Troponin Elevation

64-Year-Old Woman With Aphasia and Troponin Elevation

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

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. To assess the utility of machine learning systems for automatic discrimination of TTS and AMI. 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. Transthoracic echocardiograms of 224 patients with TTS and 224 patients with AMI were analyzed. 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. 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%). 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.

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.

Predictive Performance of the International Takotsubo Registry Score in the Diagnosis of Takotsubo Syndrome Among Women with Non-ST Segment Elevation Myocardial Infarction.

Background: The International Takotsubo Registry (InterTAK) score was developed to assess the probability of takotsubo syndrome (TTS) and to distinguish it from acute coronary syndrome, which has a similar clinical presentation. A European Society of Cardiology (ESC) consensus statement suggests invasive coronary angiography may be deferred in patients with non-ST segment elevation myocardial infarction (NSTEMI) and high probability of TTS. We aimed to determine the predictive performance of the InterTAK score in a real-world population of NSTEMIs. Materials and Methods: The InterTAK score was retrospectively calculated for consecutive female patients with NSTEMI who underwent invasive coronary angiography at two academic medical centers in New York City from March 2016 to August 2018. Results: Among 375 women with NSTEMI, 15 (4%) had InterTAK score >70, indicating high probability of TTS. Ten (67%) met ESC TTS criteria for a noninvasive strategy, among whom seven had TTS, two had spontaneous coronary artery dissection (SCAD), and one had coronary artery disease requiring revascularization. A total of 48 women (13% of cohort) had a final diagnosis of TTS. The InterTAK score had an area under the receiver operating characteristics curve (AUC) of 0.82 (95% confidence interval, 0.75-0.88) for TTS, with 21% sensitivity and 98% specificity at score >70. Conclusions: In this real-world sample of consecutive female NSTEMI patients, the InterTAK score was predictive of TTS but a high score was rare, and use of the score to obviate invasive angiography could have resulted in delay of revascularization and missed diagnosis of SCAD for a small number of patients. The InterTAK score should be used in conjunction with other clinical variables for angiographic referral.

Mortality Correlates in Patients With Takotsubo Syndrome During the COVID-19 Pandemic.

We completed a systematic review of Takotsubo syndrome (TTS) cases reported during the coronavirus disease 2019 (COVID-19) pandemic and performed clustering and feature importance analysis and statistical testing for independence on the demographic, clinical, and imaging parameters. Compared with the data before the COVID-19 pandemic, TTS was increasingly diagnosed in physical stress (mostly COVID-19 pneumonia)–triggered male patients without psychiatric/neurologic disorders, warranting further investigation to establish new reference criteria to improve diagnostic specificity. In clustering analysis, sex and inpatient mortality primarily contributed to the automated classification of the TTS. Both sex and inpatient mortality had essential correlations with COVID-19 infection/pneumonia. There is effect modification of sex on outcomes in patients with COVID-19 infection and TTS, with male patients having significantly worse inpatient mortality. Meanwhile, significantly more male patients with TTS were classified as high risk according to International Takotsubo Registry prognostic scores, suggesting that male COVID-19/TTS survivors will likely have worse long-term outcome.

Impact of Atrial Fibrillation on Outcome in Takotsubo Syndrome: Data From the International Takotsubo Registry

BackgroundAtrial fibrillation (AF) is a major risk factor for mortality. The prevalence, clinical correlates, and prognostic impact of AF in Takotsubo syndrome (TTS) have not yet been investigated in a large patient cohort. This study aimed to investigate the prevalence, clinical correlates, and prognostic impact of AF in patients with TTS.Methods and ResultsPatients with TTS were enrolled from the International Takotsubo Registry, which is a multinational network with 26 participating centers in Europe and the United States. Patients were dichotomized according to the presence or absence of AF at the time of admission. Of 1584 patients with TTS, 112 (7.1%) had AF. The mean age was higher (P<0.001), and there were fewer women (P=0.046) in the AF than in the non‐AF group. Left ventricular ejection fraction was significantly lower (P=0.001), and cardiogenic shock was more often observed (P<0.001) in the AF group. Both in‐hospital (P<0.001) and long‐term mortality (P<0.001) were higher in the AF group. Multivariable Cox regression analysis revealed that AF was independently associated with higher long‐term mortality (hazard ratio, 2.31; 95% CI, 1.50–3.55; P<0.001). Among patients with AF on admission, 42% had no known history of AF before the acute TTS event, and such patients had comparable in‐hospital and long‐term outcomes compared with those with a history of AF.ConclusionsIn patients presenting with TTS, AF on admission is significantly associated with increased in‐hospital and long‐term mortality rates. Whether antiarrhythmics and/or cardioversion are beneficial in TTS with AF should thus be tested in a future trial.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01947621.

Ethnic comparison in takotsubo syndrome: novel insights from the International Takotsubo Registry

BackgroundEthnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes.MethodsTTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients.ResultsA total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients.ConclusionDifferences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers.Trial RegistrationURL: https://www.clinicaltrials.gov; Unique Identifier: NCT01947621.

Prognostic impact of acute pulmonary triggers in patients with takotsubo syndrome: new insights from the International Takotsubo Registry.

AimsAcute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes.Methods and resultsPatients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes.Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In‐hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long‐term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long‐term mortality (hazard ratio 2.12, 95% confidence interval 1.33–3.38; P = 0.002).ConclusionsThe present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in‐hospital course and a worse long‐term outcome.

Age-Related Variations in Takotsubo Syndrome

BackgroundTakotsubo syndrome (TTS) occurs predominantly in post-menopausal women but is also found in younger patients. ObjectivesThis study aimed to investigate age-related differences in TTS. MethodsPatients diagnosed with TTS and enrolled in the International Takotsubo Registry between January 2011 and February 2017 were included in this analysis and were stratified by age (younger: ≤50 years, middle-age: 51 to 74 years, elderly: ≥75 years). Baseline characteristics, hospital course, as well as short- and long-term mortality were compared among groups. ResultsOf 2,098 TTS patients, 242 (11.5%) patients were ≤50 years of age, 1,194 (56.9%) were 51 to 74 years of age, and 662 (31.6%) were ≥75 years of age. Younger patients were more often men (12.4% vs. 10.9% vs. 6.3%; p = 0.002) and had an increased prevalence of acute neurological (16.3% vs. 8.4% vs. 8.8%; p = 0.001) or psychiatric disorders (14.1% vs. 10.3% vs. 5.6%; p < 0.001) compared with middle-aged and elderly TTS patients. Furthermore, younger patients had more often cardiogenic shock (15.3% vs. 9.1% vs. 8.1%; p = 0.004) and had a numerically higher in-hospital mortality (6.6% vs. 3.6% vs. 5.1%; p = 0.07). At multivariable analysis, younger (odds ratio: 1.60; 95% confidence interval: 0.86 to 3.01; p = 0.14) and older age (odds ratio: 1.09; 95% confidence interval: 0.66 to 1.80; p = 0.75) were not independently associated with in-hospital mortality using the middle-aged group as a reference. There were no differences in 60-day mortality rates among groups. ConclusionsA substantial proportion of TTS patients are younger than 50 years of age. TTS is associated with severe complications requiring intensive care, particularly in younger patients.

Impact of aspirin on takotsubo syndrome: a propensity score-based analysis of the InterTAK Registry.

The aim of the present study was to investigate the impact of aspirin on prognosis in takotsubo syndrome (TTS). Patients from the International Takotsubo (InterTAK) Registry were categorized into two groups based on aspirin prescription at discharge. A comparison of clinical outcomes between groups was performed using an adjusted analysis with propensity score (PS) stratification; results from the unadjusted analysis were also reported to note the effect of the PS adjustment. Major adverse cardiac and cerebrovascular events (MACCE: a composite of death, myocardial infarction, TTS recurrence, stroke or transient ischaemic attack) were assessed at 30-day and 5-year follow-up. A total of 1533 TTS patients with known status regarding aspirin prescription at discharge were included. According to the adjusted analysis based on PS stratification, aspirin was not associated with a lower hazard of MACCE at 30-day [hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.50-3.04, P=0.64] or 5-year follow-up (HR 1.11, 95% CI 0.78-1.58, P=0.58). These results were confirmed by sensitivity analyses performed with alternative PS-based methods, i.e. covariate adjustment and inverse probability of treatment weighting. In the present study, no association was found between aspirin use in TTS patients and a reduced risk of MACCE at 30-day and 5-year follow-up. These findings should be confirmed in adequately powered randomized controlled trials. ClinicalTrials.gov Identifier: NCT01947621.

Intraventricular Thrombus Formation and Embolism in Takotsubo Syndrome: Insights From the International Takotsubo Registry.

Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×103 cells/μL emerged as independent predictors for thrombus formation or embolism. Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

Clinical Features and Outcomes of Patients With Malignancy and Takotsubo Syndrome: Observations From the International Takotsubo Registry

BackgroundClinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short‐ and long‐term outcomes in TTS patients with or without malignancy.Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short‐ and long‐term mortality. A subanalysis was performed comparing long‐term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long‐term mortality was higher in patients with malignancy (P<0.001), while short‐term outcome was comparable (P=0.17). In a subanalysis, long‐term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies (P=0.13). Malignancy emerged as an independent predictor of long‐term mortality.ConclusionsA substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS, and therefore, appropriate screening for malignancy should be considered in these patients.Clinical Trial Registration URL: http://www.clinicaltrial.gov. Unique identifier: NCT01947621.

Cardiac arrest in takotsubo syndrome: results from the InterTAK Registry.

AimsWe aimed to evaluate the frequency, clinical features, and prognostic implications of cardiac arrest (CA) in takotsubo syndrome (TTS).Methods and resultsWe reviewed the records of patients with CA and known heart rhythm from the International Takotsubo Registry. The main outcomes were 60-day and 5-year mortality. In addition, predictors of mortality and predictors of CA during the acute TTS phase were assessed. Of 2098 patients, 103 patients with CA and known heart rhythm during CA were included. Compared with patients without CA, CA patients were more likely to be younger, male, and have apical TTS, atrial fibrillation (AF), neurologic comorbidities, physical triggers, and longer corrected QT-interval and lower left ventricular ejection fraction on admission. In all, 57.1% of patients with CA at admission had ventricular fibrillation/tachycardia, while 73.7% of patients with CA in the acute phase had asystole/pulseless electrical activity. Patients with CA showed higher 60-day (40.3% vs. 4.0%, P < 0.001) and 5-year mortality (68.9% vs. 16.7%, P < 0.001) than patients without CA. T-wave inversion and intracranial haemorrhage were independently associated with higher 60-day mortality after CA, whereas female gender was associated with lower 60-day mortality. In the acute phase, CA occurred less frequently in females and more frequently in patients with AF, ST-segment elevation, and higher C-reactive protein on admission.ConclusionsCardiac arrest is relatively frequent in TTS and is associated with higher short- and long-term mortality. Clinical and electrocardiographic parameters independently predicted mortality after CA.

Long-Term Prognosis of Patients With Takotsubo Syndrome

BackgroundPrognosis of Takotsubo syndrome (TTS) remains controversial due to scarcity of available data. Additionally, the effect of the triggering factors remains elusive. ObjectivesThis study compared prognosis between TTS and acute coronary syndrome (ACS) patients and investigated short- and long-term outcomes in TTS based on different triggers. MethodsPatients with TTS were enrolled from the International Takotsubo Registry. Long-term mortality of patients with TTS was compared to an age- and sex-matched cohort of patients with ACS. In addition, short- and long-term outcomes were compared between different groups according to triggering conditions. ResultsOverall, TTS patients had a comparable long-term mortality risk with ACS patients. Of 1,613 TTS patients, an emotional trigger was detected in 485 patients (30%). Of 630 patients (39%) related to physical triggers, 98 patients (6%) had acute neurologic disorders, while in the other 532 patients (33%), physical activities, medical conditions, or procedures were the triggering conditions. The remaining 498 patients (31%) had no identifiable trigger. TTS patients related to physical stress showed higher mortality rates than ACS patients during long-term follow-up, whereas patients related to emotional stress had better outcomes compared with ACS patients. ConclusionsOverall, TTS patients had long-term outcomes comparable to age- and sex-matched ACS patients. Also, we demonstrated that TTS can either be benign or a life-threating condition depending on the inciting stress factor. We propose a new classification based on triggers, which can serve as a clinical tool to predict short- and long-term outcomes of TTS. (International Takotsubo Registry [InterTAK Registry]; NCT01947621)

P919Clinical characteristics of patients with cancer and takotsubo cardiomyopathy - Observations from the international takotsubo registry

P919Clinical characteristics of patients with cancer and takotsubo cardiomyopathy - Observations from the international takotsubo registry