While the most recent evidence suggests a lack of benefit, antithrombotic therapy is still extensively prescribed in patients with Takotsubo syndrome (TTS). The objective of this study was to determine whether patients with TTS benefit from anti-aggregation, in terms of either short-term or long-term outcomes. A systematic review and meta-analysis was conducted. A comprehensive search of the literature included MEDLINE, Cochrane Library, Clinicaltrials.gov, EU Clinical Trial Register, References, and contact with the authors. Methodological quality assessment and data extraction were systematically performed. The review adhered to the PRISMA framework guidelines. A total of 86 citations were identified, six being eligible for inclusion, for a total of 1997 patients. One of them considered both short-term and long-term outcomes. One reported outcomes during the index event, while the remaining four focused on potential long-term benefits. They were all retrospective cohort studies.Based on our data, the long-term use of antiplatelet therapy (AT) led to a significantly higher incidence of the composite outcome (OR: 1.54; 95% CI 1.09–2.17; p = 0.014) and overall mortality (OR 1.72; 95% CI 1.07–2.77; p = 0.027). The analysis did not show a statistically significant difference in TTS recurrences, stroke/TIA, and MI or CAD worsening with AT compared with no anti-aggregation. The AT in this settings did not show any clear benefit in improving the long-term outcomes, and it may be even detrimental and it may be detrimental. These results warrant further future research and the design of adequately powered randomized controlled trials focusing on the impact of aspirin on the outcomes in patients presenting with TTS.

Coronary microvascular dysfunction (CMD) has been proposed as a key driver in the etiopathogenesis of Takotsubo syndrome (TTS), likely related to an “adrenergic storm” upon a susceptible microvascular circulation. The aim of our manuscript was to assess CMD in patients with TTS through the computation of the angiography-derived index of microcirculatory resistance (IMR) and its correlation with clinical presentation. Coronary angiograms of 41 consecutive TTS patients were retrospectively analyzed to derive angiography-based indices of CMD. Three indices (NH-IMRangio, AngioIMR and A-IMR) were calculated based on quantitative flow ratio. CMD was defined as an IMRangio value ≥ 25 units. The correlation between CMD and clinical presentation was then assessed. Median age was 76 years, 85.7% were women and mean left ventricular ejection fraction (LVEF) at first echocardiogram was 41.2%. Angiography-derived IMR was higher in left anterior descending artery (LAD) than circumflex and right coronary artery with either NH-IMRangio (53.9 ± 19.8 vs 35.8 ± 15.4 vs 40.8 ± 18.5, p-value < 0.001), AngioIMR (47.2 ± 17.3 vs 31.8 ± 12.2 vs 37.3 ± 13.7, p-value < 0.001) or A-IMR (52.7 ± 19 vs 36.1 ± 14.1 vs 41.8 ± 16.1, p-value < 0.001). All patients presented CMD with angiography-derived IMR ≥ 25 in at least one territory with each formula. Angiography-derived IMR in LAD territory was significantly higher in patients presenting with LVEF impairment (≤ 40%) than in those with preserved ventricular global function (NH-IMRangio: 59.3 ± 18.1 vs 46.3 ± 16.0 p-value = 0.030; AngioIMR: 52.9 ± 17.8 vs 41.4 ± 14.2, p-value = 0.037; A-IMR: 59.2 ± 18.6 vs 46.3 ± 17.0, p-value = 0.035). CMD assessed with angiography-derived IMR is a common finding in TTS and it is inversely correlated with LV function. The available formulas have a substantial superimposable diagnostic performance in assessing coronary microvascular function.

Background: The present study aimed to examine longitudinal trends in hospitalizations for acute coronary syndrome (ACS) before and during the COVID-19 pandemic, by reviewing the data from 13 hospitals of the Veneto Region, in the north-east of Italy. Methods: We performed a multicenter, retrospective analysis including all the consecutive patients presenting with ACS and other acute cardiovascular (CV) conditions (defined as heart failure, arrhythmias, cardiac arrest and venous thromboembolism) hospitalized in 13 different hospitals of the Veneto Region covering a population of 2,554,818 inhabitants, during the first (between 15 March 2020 and 30 April 2020) and second (between 15 November 2020 and 30 December 2020) COVID-19 pandemic waves (the 2020 cohort). Data were compared with those obtained at the same time-windows of years 2018 and 2019 (the historical cohorts). Results: Compared to the historical cohorts, a significant decrease in the number of ACS cases was observed in 2020 (−27.3%, p = 0.01 and −32%, p < 0.001, comparing 2018 versus 2020 and 2019 and 2020, respectively). The proportion of patients hospitalized for acute CV conditions decreased during the first and second wave COVID-19 pandemic when compared to the historical cohorts (−36.5%, p < 0.001 and −40.6%, p < 0.001, comparing 2018 versus 2020 and 2019 and 2020, respectively). Pearson’s correlation evidenced a significant inverse relationship between the number of COVID-19 cases and both ACS hospital admissions (r = −0.881, p = 0.005) and hospitalizations for acute CV conditions (r = −0.738, p = 0.01), respectively. Conclusions: The decrease in hospitalizations for ACS and other acute CV conditions will strongly affect future patients’ management since undiagnosed nonfatal CV events represent a source of increased (and unknown) CV morbidity and mortality.

Background and purpose Coronary microvascular dysfunction (CMD) has been proposed as a key driver in the etiopathogenesis of Takotsubo syndrome (TTS), likely related to an “adrenergic storm” upon a susceptible microvascular circulation. The aim of our manuscript was to assess and quantify CMD in patients with TTS through angiography-derived index of microcirculation (IMR) and evaluate its correlation with clinical presentation. Methods Coronary angiograms of 41 consecutive TTS patients were retrospectively offline analyzed to derive angiography-based indices of CMD. Three recently developed indices (NH-IMRangio, AngioIMR and A-IMR) were calculated and compared based on Quantitative Flow Reserve (QFR) analysis. CMD was defined as an IMRangio ≥25 units. The correlation between CMD and clinical presentation and outcomes was then assessed. Results Median age was 76 years, 85.7% were women and mean left ventricular ejection fraction (LVEF) at first echocardiogram was 41.2%. Angiography-derived IMR was higher in Left Anterior Descending artery (LAD) than Circumflex artery (LCX) and Right Coronary artery (RCA) with either NH-IMRangio (52.7 vs 35.3 vs 41.4), AngioIMR (47.2 vs 31.8 vs 37.3) or A-IMR (52.7 vs 36.1 vs 41.8). All patients presented CMD with angiography-derived IMR ≥25 in at least one territory with each formula. Angiography-derived IMR in LAD territory was significantly higher in patients presenting with LVEF impairment (≤40%) than in those with preserved ventricular global function (NH-IMRangio: 59.3 vs 46.3, p. value=0.030; AngioIMR: 52.9 vs 41.4, p-value=0.037; A-IMR: 59.2 vs 46.3, p-value=0.035). Conclusion CMD, assessed with angiography-derived IMR, is a common finding in TTS and it is inversely correlated with LV function. The available formulas have a substantial superimposable diagnostic performance in assessing coronary microvascular function. Funding Acknowledgement Type of funding sources: None.

Aims Takotsubo syndrome (TTS) is an acute and reversible heart failure syndrome that, at presentation, mimics acute myocardial infarction. The most common echocardiographic manifestation is the so-called ‘apical ballooning’, but other much less common wall motion patterns have been described. The pathophysiology of the syndrome is not fully understood, but there is considerable evidence that sympathetic stimulation plays a central role. The prevalence of this syndrome is higher in post-menopausal women and in most cases, but not invariably, precipitated by an emotional or physical triggering event. A close relation between brain and circulatory system has been observed and for this reason psychiatric and neurologic disorders are often recognized as precipitating conditions. Although many risk factor persist after the acute manifestation, Takotsubo recurrences do represent an exception, especially in the absence of a clear precipitating event. Methods and results A 70-year-old woman was admitted for anginal pain associated with ischaemic electrocardiographic alterations and elevation of cardiac biomarkers. The coronary angiography with left ventriculogram and the echocardiographic findings were consistent with a diagnosis of mid-ventricular Takotsubo. Cardiac magnetic resonance confirmed the absence of an ischaemic pattern or evidence of infectious myocarditis. This case represents a recurrence of TTS, in fact two years earlier the patient was hospitalized to our division for stress cardiomyopathy with typical apical ballooning. Also in the present occasion, she had a favorable clinical course, with a complete recovery of the cardiac function at subsequent evaluations. The unicity of this case lies above all in the absence of a clear trigger event. Although, an altered mental status was present because the patient suffered from anxiety and depression on pharmacological treatment, with periods of exacerbation but not in occasion of the recurrence. Conclusions TTS is not a benign condition, with recurrence being possible even in the absence of precipitating events. Based on registry data, annual rate of Takotsubo recurrence is 1.5–1.8% and is estimated to reach 4% in life. A variable TTS pattern at recurrence is common in up to 20% of cases. Our paper reports a unique case of recurrent Takotsubo syndrome with variable patterns of ventricular involvement, with neither physical nor psychological trigger. Nevertheless, for what concerns our case, the psychiatric condition the patient suffered from, could have played a role of permanent status of sympathetic activation, that in the end elicitates the occurrence of the syndrome. A better understanding of the pathophysiology of the syndrome is needed to find evidence-based therapeutic strategies that could prevent recurrence.