Cardiac troponin elevation and mortality in takotsubo syndrome: New insights from the international takotsubo registry.

BACKGROUND: The clinical relevance of cardiac troponin (cTn) elevation in takotsubo syndrome (TTS) remains uncertain. The present study sought to investigate the role of cardiac troponin (cTn) elevations in mortality prediction of patients with Takotsubo syndrome (TTS). METHODS: Patients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to February 2020 with available data on peak cTn levels were included in the analysis. Peak cTn levels during the index hospitalization were used to define clinically relevant myocardial injury. The threshold at which clinically relevant myocardial injury drives mortality at 1 year 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. 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 =.002). Clinically relevant myocardial injury was related to an increased 5-year mortality risk in patients with apical TTS (adjusted HR 1.57, 95% CI 1.21-2.03, p =.001), in presence of physical stressors (adjusted HR 1.60, 95% CI 1.22-2.11, p =.001), and in absence of emotional stressors (adjusted HR 1.49, 95% CI, 1.17-1.89, p =.001). CONCLUSION: 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.

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.

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

BACKGROUND: Ethnic 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. METHODS: TTS 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. RESULTS: A 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. CONCLUSION: Differences 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 REGISTRATION: URL: 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.

AIMS: Acute 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 RESULTS: Patients 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). CONCLUSIONS: The 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.