BackgroundLeft ventricular (LV) thrombi during Takotsubo syndrome represent a potential complication and can be associated with cerebrovascular embolic events. The aim of this study was to evaluate the exact incidence, predictors, and management strategies of LV thrombi in patients with Takotsubo syndrome.Methods and ResultsWe enrolled 541 consecutive patients in a multicenter international registry. Clinical features and echocardiographic data at admission, during hospitalization, and after 3 months were evaluated. Survival rates for long‐term follow‐up (mean 984±908 days) were recorded. Twelve Takotsubo syndrome patients (2.2%) developed LV thrombi (all female presenting with apical ballooning pattern). All patients with LV thrombi were treated with oral anticoagulation therapy; however, 2 (17%) had a stroke before treatment initiation. These patients were characterized by a higher prevalence of ST‐elevation (56% versus 16%; P<0.001) and higher troponin I levels (10.8±18.3 ng/mL versus 3.5±4.3 ng/mL; P=0.001) as compared with those without LV thrombi. At multivariate analysis including age, sex, LV ejection fraction, ST‐elevation at admission, and apical ballooning pattern, troponin I level >10 ng/mL was the only predictor for LV thrombosis (hazard ratio 6.6, confidence interval, 1.01–40.0; P=0.04). After 3 months all LV thrombi disappeared. Oral anticoagulation therapy was interrupted in all patients except 1. At long‐term follow‐up, the survival rate was not different between patients with and without LV thrombi (84% versus 85%; P=0.99).Conclusions LV thrombi have a relatively low incidence among patients with Takotsubo syndrome and were detected in female patients with apical ballooning pattern and increased troponin levels. Oral anticoagulation therapy for 3 months seems reasonable in these high‐risk patients.

Background: Efficacy of chronic drug therapy in prevention of stress-induced cardiomyopathy recurrences is not well established. We therefore aimed to evaluate in this meta-analysis whether pharmacological treatment can effectively prevent takotsubo cardiomyopathy (TTC) recurrences, according to available studies. Hypothesis: There is no evidence for preventing TTC recurrence by drug therapy. Methods: After a PubMed search, we conducted a meta-analysis of available studies (clinical nonrandomized registries) on efficacy of drug therapy in preventing recurrence of TTC. Results: A total of 23 (4.5%) TTC recurrences occurred in the 511 patients included in the analysis. Seven studies on the effects of β-blockers on prevention of TTC recurrence were evaluated; the odds ratio (OR) was 0.44 and the 95% confidence interval (CI) was 0.15-1.31. In 5 studies on the effects of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, the OR was 0.42 and the 95% CI was 0.08-2.36; in 3 studies on statins, the OR was 0.74 and the 95% CI was 0.07-7.3; and in 4 studies on aspirin, the OR was 0.33 with a 95% CI of 0.05-2.17 (P value not significant in all cases). Conclusions: A meta-analysis of the efficacy of different medications through the clinical TTC registries available showed no clinical evidence for a standard drug treatment in the chronic management of TTC. β-Blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, statins, and aspirin do not seem to significantly reduce recurrences of TTC. Randomized, adequately powered studies are needed to further assess this issue. IntroductionTakotsubo cardiomyopathy (TTC) is a rapidly reversible form of acute heart failure occurring mainly in postmenopausal women after an episode of physical or emotional stress 1 and is associated with a typical left ventricular (LV) contraction pattern. 2 Increased catecholamine levels were thought to be the primary precipitator of the condition, 3 but the exact mechanism is still not well elucidated. 4,5 The initial treatment for TTC is usually the same as adopted for acute heart failure, except for contraindication to β-adrenergic inotropes 6 ; data on the efficacy of chronic pharmacological therapy, however, are scanty. Despite its relatively good long-term prognosis, 7 recurrences of TTC are not infrequent, with a rate ranging from 5% to 11.4% within the first 4 years and an incidence per year of 2.4%. 8,9 β-Blockers are commonly used chronically to prevent TTC recurrence, but, given the rarity of TTC, there are no randomized studies supporting this approach.We therefore conducted a meta-analysis of currently available studies to evaluate whether drug therapy can effectively prevent TTC recurrences.

IMPORTANCE Takotsubo syndrome (TTS) is an acute, reversible heart failure syndrome featured by significant rates of in-hospital complications. There is a lack of data for risk stratification during hospitalization.OBJECTIVE To derive a simple clinical score for risk prediction of in-hospital complications among patients with TTS. DESIGN, SETTING, AND PARTICIPANTSIn this prognostic study, 1007 consecutive patients were enrolled in the German and Italian Stress Cardiomyopathy (GEIST) registry from July 1, 2007, through December 31, 2017, and identified as the derivation cohort; 946 patients were enrolled in the Spanish Registry for Takotsubo Cardiomyopathy (RETAKO) as the external score validation. An admission risk score was developed using a stepwise multivariable regression analysis from 2 registries. Data analysis was performed from March 1, 2018, through July 31, 2018. MAIN OUTCOMES AND MEASURESIn-hospital complications were defined as death, pulmonary edema, need for invasive ventilation, and cardiogenic shock. Four variables were identified as independent predictors of in-hospital complications and were used for the score: male sex, history of neurologic disorder, right ventricular involvement, and left ventricular ejection fraction (LVEF). RESULTSOf the 1007 patients enrolled in the GEIST registry, 107 (10.6%) were male, with mean (SD) age of 69.8 (11.4) years. Overall rate of in-hospital complications was 23.3% (235 of 1007) (death, 4.0%; pulmonary edema, 5.8%; invasive ventilation, 6.4%; and cardiogenic shock, 9.1%). The GEIST prognosis score was derived by providing 20 points each for male sex and history of neurologic disorders and 30 points for right ventricular involvement and then subtracting the value in percent of LVEF (decimal values between 0.15 and 0.70). Score accuracy on area under the receiver operating characteristic curve analysis was 0.71, with a negative predictive power of 87% with scores less than 20. External validation in the RETAKO population (124 [13.1%] male; mean [SD] age, 69.5 [14.9] years) revealed an area under the curve of 0.73 (P = .46 vs GEIST xderivation cohort). Stratification into 3 risk groups (<20, 20-40, and >40 points) classified 316 patients (40.9%) as having low risk; 342 (44.3%) as having intermediate risk, and 114 (14.8%) as having high risk of complications. The observed in-hospital complication rates were 12.7% for low-risk patients, 23.4% for intermediate-risk patients, and 58.8% for high-risk patients (P< .001 for trend). After 2.6 years of follow-up, patients with in-hospital complications had significantly higher rates of mortality than those without complications (40% vs 10%, P = .01). CONCLUSIONS AND RELEVANCEThe GEIST prognostic score may be useful in early risk stratification for TTS. High-risk patients with TTS may require an intensive care unit stay, and low-risk patients with TTS could be discharged within a few days. In-hospital complications in patients with TTS may be associated with increased risk of long-term mortality.

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Background Atrioesophageal fistula (AEF) is a worrisome complication of atrial fibrillation (AF) ablation. Its clinical manifestations and time course are unpredictable and may contribute to diagnostic and treatment delays. We conducted a systematic review of all available cases of AEF, aiming at characterizing clinical presentation, time course, diagnostic pitfalls, and outcomes. Methods The digital search retrieved 150 studies containing 257 cases, 238 (92.6%) of which with a confirmed diagnosis of AEF and 19 (7.4%) of pericardioesophageal fistula. Results The median time from ablation to symptom onset was 21 days (interquartile range [IQR]: 11–28). Neurological abnormalities were documented in 75% of patients. Compared to patients seen by a specialist, those evaluated at a walk‐in clinic or community hospital had a significantly greater delay between symptom onset and hospital admission (median: 2.5 day [IQR: 1–8] vs. 1 day [IQR: 1–5); p = .03). Overall, 198 patients underwent a chest scan (computed tomography [CT]: 192 patients and magnetic resonance imaging [MRI]: 6 patients), 48 (24.2%; 46 CT and 2 MRI) of whom had normal/unremarkable findings. Time from hospital admission to diagnostic confirmation was significantly longer in patients with a first normal/unremarkable chest scan (p < .001). Overall mortality rate was 59.3% and 26.0% survivors had residual neurological deficits at the time of discharge. Conclusions Since healthcare professionals of any specialty might be involved in treating AEF patients, awareness of the clinical manifestations, diagnostic pitfalls, and time course, as well as an early contact with the treating electrophysiologist for a coordinated interdisciplinary medical effort, are pivotal to prevent diagnostic delays and reduce mortality.

SUMMARYBackground: Left ventricular outflow tract obstruction (LVOTO) may complicate an episode of Takotsubo cardiomyopathy (TTC), potentially leading to cardiogenic shock. Betablockers are considered the most suitable treatment for such complication. Aim of the study: The objective of this study was to evaluate the hemodynamic effects, safety, and feasibility of a selective beta-blocker (b1) with a short half-life, esmolol, in subjects with a TTC episode. Methods: Ninety-six consecutive patients with TTC were enrolled in a multicenter registry. The hemodynamic and echocardiographic effects of esmolol (0.15-0.3 mg/kg/min) were analyzed in nine consecutive patients with LVOTO. Clinical course of patients, hemodynamics, days of hospitalization, LV function, and adverse events at follow-up were recorded. Results: Left ventricular outflow tract obstruction was present in 10 (10.4%) of 96 patients. Patients with LVOTO were older and had higher values of troponin-I at admission. LV ejection fraction at admission (36.1 AE 8.4%) significantly improved at discharge (51.4 AE 6.9%, P = 0.001). Among patients treated with esmolol infusion, LVOT pressure gradient before treatment was 47.6 AE 16.6 mmHg and after 18.2 AE 2.3 mmHg (P = 0.0091). Systolic blood pressure decreased from 123.8 AE 29.1 to 112.6 AE 12.7 mmHg (P = 0.1537). Mean hospital stay was 9 AE 2 days. No adverse events were observed during hospitalization and at follow-up. Conclusions: Esmolol infusion was temporally associated with reduction in intraventricular gradient and systemic blood pressure in patients with TTC and LVOTO. Further controlled studies are warranted to confirm these preliminary findings.

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