Aims: Takotsubo syndrome (TTS) is an acute heart failure syndrome, which shares many features with acute coronary syndrome (ACS). Although TTS was initially described with angiographically normal coronary arteries, smaller studies recently indicated a potential coexistence of coronary artery disease (CAD) in TTS patients. This study aimed to determine the coexistence, features, and prognostic role of CAD in a large cohort of patients with TTS. Methods and results: Coronary anatomy and CAD were studied in patients diagnosed with TTS. Inclusion criteria were compliance with the International Takotsubo Diagnostic Criteria for TTS, and availability of original coronary angiographies with ventriculography performed during the acute phase. Exclusion criteria were missing views, poor quality of angiography loops, and angiography without ventriculography. A total of 1016 TTS patients were studied. Of those, 23.0% had obstructive CAD, 41.2% had non-obstructive CAD, and 35.7% had angiographically normal coronary arteries. A total of 47 patients (4.6%) underwent percutaneous coronary intervention, and 3 patients had acute and 8 had chronic coronary artery occlusion concomitant with TTS, respectively. The presence of CAD was associated with increased incidence of shock, ventilation, and death from any cause. After adjusting for confounders, the presence of obstructive CAD was associated with mortality at 30 days. Takotsubo syndrome patients with obstructive CAD were at comparable risk for shock and death and nearly at twice the risk for ventilation compared to an age- and sex-matched ACS cohort. Conclusions: Coronary artery disease frequently coexists in TTS patients, presents with the whole spectrum of coronary pathology including acute coronary occlusion, and is associated with adverse outcome. Trial registration: ClinicalTrials.gov number: NCT01947621.

Objective Patients with Takotsubo syndrome (TTS) present an acute microvascular dysfunction that leads to an impaired myocardial perfusion and, in more severe forms, an impaired epicardial flow. However, clinical relevance of a delayed coronary flow, the coronary slow flow (CSF), has never been investigated. We studied the prognostic value of CSF occurring in the acute phase of TTS. Methods This cohort study prospectively evaluated patients with a diagnosis of TTS. CSF was defined as angiographically non-obstructive coronary arteries with thrombolysis in myocardial infarction-2 flow. The incidence of overall mortality and major adverse cardiovascular events (MACEs), defined as the composite of TTS recurrence, cardiac rehospitalisation, cerebrovascular events and mortality, was assessed at follow-up. Results We enrolled 101 patients (mean age 71.0±11.1 years, 86 (85.1%) female); CSF occurred in 18 (17.8%) patients. At admission, patients with CSF presented more frequently with Killip class III/IV, moderate-to-severe left ventricle systolic dysfunction and right ventricle dysfunction. During the index admission, patients with CSF had a higher rate of intrahospital complications (12 (66.7%) vs 28 (33.7%), p=0.01). At long-term follow-up, patients with CSF had a significantly higher occurrence of overall mortality (9 (50%) vs 19 (22.9%), p=0.011), mainly due to non-cardiac causes (89.3%), and a higher rate of MACE (10 (55.5%) vs 27 (32.5%), p=0.06). At multivariable Cox regression, CSF was independently associated with death from any causes. Conclusions Patients with TTS presenting with CSF have a worse clinical presentation with a higher rate of intrahospital complications and a poor long-term clinical outcome.

Background: Atrial 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 Results: Patients 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. Conclusions: In 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. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01947621.

Aims: Takotsubo syndrome (TTS) is associated to serious adverse in-hospital complications. We evaluated the role of invasively assessed left ventricular end-diastolic pressure (LVEDP) for predicting in-hospital complications in TTS patients compared to the most widely used echocardiographic parameters of ventricular function.Methods and Results : We prospectively enrolled 130 patients (mean age 71.2 ± 11.3 years, 114 [87.7%] female) with TTS. Invasive measurement of LVEDP was performed at the time of cardiac catheterization. The rate of in-hospital complications (composite of acute heart failure, life-threatening arrhythmias and all-cause death) was examined. In-hospital complications occurred in 37 (28.5%) patients. Patients who experienced in-hospital complications had a higher prevalence of neurological trigger and lower prevalence of emotional trigger, higher LVEDP and mean E/e′ ratio and lower LV ejection fraction (LVEF) values compared to those who did not experience in-hospital complications. At multivariate logistic regression, higher LVEDP [odds ratio (OR) 1.12, 95% confidence interval (CI) [1.05–1.20], P < 0.001] and lower LVEF (OR 0.95, 95% CI [0.91–0.99], P = 0.011) remained independently predictors of in-hospital complications, while emotional trigger was associated to a lower risk (OR 0.24, 95% CI [0.06–0.96], P = 0.044). The area under the curve (AUC) for LEVDP in the prediction of in-hospital events was 0.776 (95% CI [0.69–0.86], P <0.001, with a sensitivity and specificity of 95% and 58% using a LVEDP cut-off value of 22.5 mmHg). The AUC was significantly higher for LVEDP than for E/e′ ratio (P = 0.037).Conclusions : LVEDP measured at the time of catheterization may help in identifying TTS patients at higher risk of cardiovascular deterioration with relevant therapeutic implications.

Takotsubo syndrome (TTS) is characterized by transient left ventricular wall motion anomalies associated with coronary microvascular dysfunction in the absence of culprit lesions of epicardial coronary arteries.¹ The clinical presentation of TTS resembles that of typical acute coronary syndrome (ACS).² Despite coronary angiography being the gold standard for TTS diagnosis, its limitations and unessential role in disease management necessitate non-invasive diagnostic methods.² Patients with TTS exhibit distinctive patterns of classic cardiac biomarkers compared to patients with ACS. Specifically, TTS is associated with higher brain natriuretic peptide (BNP) levels attributed to heightened filling pressures, and conversely, lower levels of troponin or creatine kinase (CK), as a consequence of distinct pathophysiological mechanisms.^2,3 These variations in biomarker levels have been proposed as valuable indicators in differentiating these two entities from another.⁴ However, although previously proposed ratios of classic cardiac biomarkers exhibit promise in distinguishing TTS from ACS, their applicability was restricted by small sample sizes and a lack of validation.^5–9 Thus, the present study aims to validate these ratios in the largest database dedicated to TTS worldwide, the International Takotsubo (InterTAK) Registry.¹