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Background: To assess whether hypoxia, as can be found in obstructive sleep apnea syndrome, is causally associated with the development of heart failure through a direct effect on calcium leakage from the sarcoplasmic reticulum. Methods: The impact of hypoxia on sarcoplasmic reticulum calcium leakage and expression of RyR2 (ryanodine receptor2) and SERC2a (sarcoplasmic reticulum Ca2+ATPase 2a) was investigated together with the outcomes of JTV-519 and S107 treatment. HL-1 cardiomyocytes were cultured for 7 days on gas-permeable cultureware under control (12% O2) or hypoxic (1% O2) conditions with or without JTV-519 or S107. SRCL was assessed using a Fluo-5N probe. Gene and protein expression was analyzed using qPCR and western blotting. Results: Hypoxic exposure increased sarcoplasmic reticulum calcium leakage by 39% and reduced RyR2 gene expression by 52%. No effect on RyR2 protein expression was observed. Treatment with 1µM JTV-519 reduced sarcoplasmic reticulum calcium leakage by 52% and 35% under control and hypoxic conditions, respectively. Administration of 1 µM JTV-519 increased RyR2 gene expression by 89% in control conditions. No effect on SRCL, RyR2, or SERC2a gene, or protein expression was observed with S107 treatment. Conclusion: Hypoxia increased sarcoplasmic reticulum calcium leakage which was ameliorated by JTV-519 treatment independently of gene or protein expression. JTV-519 rep-resents a possible treatment for obstructive sleep apnea-associated HF.

This research aims to propose a model adding to the competitiveness of companies by identifying factors that determine the profitability of the selected companies (both publicly traded and unquoted private companies of all sizes). Another aim is to prove a dichotomy between the motivation of equity holders and senior lenders as far as acceptable financial leverage is concerned. The paper is innovative based on its combination of several different factors influencing corporate profitability (i.e. firm-specific effects: current ratio, labor cost ratio, working capital financing ratio, long-term financing ratio, return on sales, age of the firm; industry-specific effects and other macroeconomic effects) and by assessing determinants concerning the interests of shareholders and other stakeholders using a panel regression analysis with fixed effects. The authors prove that the determinants of the operating performance of Czech trading companies differ substantially when the performance is measured by ROA or by ROE. This clearly shows discrepancies between the equity holder interest to maximize their returns on investment and the other stakeholder interests. Specifically, the authors have found that the leverage, both in terms of working capital and long-term financing, negatively impacts returns on assets. On the other hand, it positively impacts returns for equity holders both in the Wholesale and Retail sub-samples. Interestingly, other determinants of operating performance, such as capital intensity, labor cost ratio, historical profitability, and macroeconomic variables, are of comparable significance, impacting both the ROA and ROE analyses.

Abstract 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.

Recent studies have suggested a pathogenetic link between impaired mitochondria and Takotsubo syndrome (TTS), which is closely connected with catecholamine overstimulation, poor outcomes, and changes in lipid metabolism. We investigated the changes in lipid metabolism at the level of fatty acid β-oxidation and changes in the intracellular lipidomic spectrum. The immortalized cell line of HL-1 cardiomyocytes was used in this study as an established in vitro model of TTS. The cells were exposed to the non-selective β-agonist isoprenaline (ISO) for acute (2 h) and prolonged (24 h) periods. We investigated the impact on mitochondrial adenosine 5’-triphosphate (ATP) production and β-oxidation using real-time cell metabolic analysis, total lipid content, and changes in the lipidomic spectrum using high-performance liquid chromatography (HPLC) and mass spectrometry. Furthermore, modifications of selected lipid transporters were determined using real-time – polymerase chain reaction (RT-PCR) and/or Western blot techniques. By choosing this wide range of targets, we provide a detailed overview of molecular changes in lipid metabolism during catecholamine overstimulation. The present study demonstrates that acute exposure to ISO decreased ATP production by up to 42.2%, and prolonged exposure to ISO decreased β-oxidation by 86.4%. Prolonged exposure to ISO also increased lipid accumulation by 4%. Lipid spectrum analysis of prolonged exposure to ISO showed a reduced concentration of cardioprotective and an increased concentration of lipotoxic lipid molecules during long-term exposure. Decreased lipid utilization can lead to higher intracellular lipid accumulation and the formation of lipotoxic molecules. Changes in the lipid spectrum can induce pathophysiological signaling pathways leading to cardiomyocyte remodeling or apoptosis. Thus, changes in lipid metabolism induced by excessive doses of catecholamines may cause TTS and contribute to a progression of heart failure, which is at increased risk after a TTS episode.

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

Abstract Apoptosis plays an important role in the myocardial loss after acute myocardial infarction and participates in the process of subsequent left ventricular remodeling and development of symptomatic heart failure. Finding a sensitive apoptotic marker that would help in prognostic stratification of patients after acute myocardial infarction and offer new therapeutic strategies is thus of a great importance. Several studies suggest that tumor necrosis factor-related apoptosis inducing ligand (TRAIL) represents a very promising marker of prognosis in patients with acute myocardial infarction. This review article provides an overview of current knowledge on the role of apoptosis in ischemic heart disease and highlights potentially beneficial apoptotic markers in clinical practice.

Background Left ventricular (LV) recovery in takotsubo syndrome (TTS) occurs over a wide‐ranging interval, varying from hours to weeks. We sought to investigate the clinical predictors and prognostic impact of recovery time for TTS patients. Methods and Results TTS patients from the International Takotsubo Registry were included in this study. Cut‐off for early LV recovery was determined to be 10 days after the acute event. Multivariable logistic regression was used to assess factors associated with the absence of early recovery. In‐hospital outcomes and 1‐year mortality were compared for patients with versus without early recovery. We analyzed 406 patients with comprehensive and serial imaging data regarding time to recovery. Of these, 191 (47.0%) had early LV recovery and 215 (53.0%) demonstrated late LV improvement. Patients without early recovery were more often male (12.6% versus 5.2%; P=0.011) and presented more frequently with typical TTS (76.3% versus 67.0%, P=0.040). Cardiac and inflammatory markers were higher in patients without early recovery than in those with early recovery. Patients without early recovery showed unfavorable 1‐year outcome compared with patients with early recovery (P=0.003). On multiple logistic regression, male sex, LV ejection fraction

Background Clinical 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

BACKGROUND: Apoptosis plays an important role in the development of heart failure. The aim of the prospectively designed study was to assess whether the concentration of apoptotic markers apoptosis-stimulating fragment (Fas, CD95/APO-1) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can predict prognosis in patients with acute coronary syndromes. METHODS: The concentrations of soluble Fas and TRAIL were determined in 295 patients with acute coronary syndromes. The status of all patients was evaluated at 6 months. The primary goal was a composite end-point of death and hospitalization for heart failure. The secondary end-points were re-MI, death alone and stroke alone. RESULTS: During the median follow-up of 6 months, 26 patients experienced the composite end-point. Using multivariate logistic regression, the concentration of TRAIL was the strongest significant and independent predictor of composite end-point (OR 0.11 (95% CI 0.03-0.45), p = 0.002). Low concentration was associated with poor prognosis of patients. Other significant predictors of composite end-point were serum creatinine (OR 7.7 (95% CI 1.1-54.5, p = 0.041) and complete revascularization (OR 0.19 (95% CI 0.05-0.78, p = 0.02). Independent significant predictors of death in the multivariate analysis were the concentration of TRAIL (OR 0.053 (95% CI 0.004-0.744), p = 0.029), older age (OR 1.20 (95% CI 1.02-1.41, p = 0.026) and serum creatinine (OR 15.1 (95% CI 1.56-145.2), p = 0.0193). Re-MI or stroke could not be predicted by any combination of obtained parameters. CONCLUSIONS: Low concentrations of soluble TRAIL represent a strong predictor of a poor prognosis in patients with acute coronary syndrome. The predictive value of TRAIL concentration is independent of age, ejection fraction, index peak troponin level, concentration of BNP or serum creatinine.

• Initial ischemic risk in ST-segment elevation myocardial infarction patients affects prognosis more than ischemic time. • Longer ischemic time increases ischemic events only in high-risk patients. • Longer ischemic time increases all-cause mortality only in high-risk patients. • Post-percutaneous coronary intervention suboptimal flow is more frequent in patients with longer ischemic time. Based on previous studies with clopidogrel, the time between acute myocardial infarction (AMI) symptoms onset and primary percutaneous coronary intervention (PCI) was proven as important prognostic factor. Our aim was to assess the relationship between symptoms onset to needle time (SNT) and procedural results and the occurrence of ischemic endpoints in primary angioplasty patients treated with potent P2Y12 inhibitors. A total of 1,131 out of 1,230 patients randomized to the Prague-18 study (prasugrel vs. ticagrelor in primary PCI) were divided into a high and a low-risk group. The effect of defined SNT on patients' ischemic endpoints and prognosis by their risk status at admission was tested. The median SNT was 3.2 hours. Longer SNTs resulted in a more frequent incidence of TIMI flow <3 post PCI (p=0.015). There were significant differences in the occurrence of the combined ischemic endpoint among the compared SNT groups at 30 days (p=0.032), and 1 year (p=0.011), with the highest incidence in the ≤1 h SNT group of patients. "Latecomers" (SNT>4 hs) in the high-risk group experienced more reinfarction within 1 year [OR (95% CI) 3.23 (1.09–9.62) p=0.035]; no difference was found in the low-risk group. In the era of intense antithrombotic medication, stratification of MI patients undergoing primary angioplasty, based on initial ischemic risk assessment affected prognosis more than symptom onset to needle time. Longer time delay was significantly related to increased incidence of ischemic events and all-cause mortality only in patients with high ischemic risk. In STEMI patients referred to primary PCI and treated with prasugrel or ticagrelor, longer symptom-to-needle times (SNT) were associated with more frequent suboptimal PCI results. Stratification of patients based on their initial ischemic risk (per TIMI criteria) proved to have more prognostic power than SNT. Compared to low-risk patients, high-risk patients had a significantly higher incidence of both ischemic events and all-cause mortality when presenting with SNT > 4 hours. Concerning early comers (SNT < 4 hours), mortality rate but not the incidence of ischemic endpoints was significantly higher in the high-risk group of patients. [Display omitted] [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF), with a prevalence of 1% to 2%, is the most common cardiac arrhythmia. Without antithrombotic treatment, the annual risk of a cardioembolic event is 5% to 6%. The source of a cardioembolic event is a thrombus, which is usually formed in the left atrial appendage (LAA). Prevention of cardioembolic events involves treatment with anticoagulant drugs: either vitamin K antagonists or, recently, novel oral anticoagulants (NOAC). The other (nonpharmacologic) option for the prevention of a cardioembolic event involves interventional occlusion of the LAA.Objective: To determine whether percutaneous LAA occlusion is noninferior to treatment with NOAC in AF patients indicated for long-term systemic anticoagulation.Study Design: The trial will be a prospective, multicenter, randomized noninferiority trial comparing 2 treatment strategies in moderate to high-risk AF patients (ie, patients with history of significant bleeding, or history of cardiovascular event(s), or a with CHA2DS2VASc ≥3 and HAS-BLED score ≥2). Patients will be randomized into a percutaneous LAA occlusion (group A) or a NOAC treatment (group B) in a 1:1 ratio; the randomization was done using Web-based randomization software. A total of 396 study participants (198 patients in each group) will be enrolled in the study. The primary end point will be the occurrence of any of the following events within 24months after randomization: stroke or transient ischemic attack (any type), systemic cardioembolic event, clinically significant bleeding, cardiovascular death, or a significant periprocedural or device-related complications.Conclusion: The PRAGUE-17 trial will determine if LAA occlusion is noninferior to treatment with NOAC in moderate- to high-risk AF patients. [ABSTRACT FROM AUTHOR]

Background--Bioresorbable vascular scaffolds (BVS) represent promising new technology, but data on their long-term outcomes in ST-segment-elevation myocardial infarction (STEMI) setting are missing. The aim was to analyze 1-year clinical and computed tomographic angiographic outcomes after BVS implantation in STEMI. Methods and Results--PRAGUE-19 is a prospective multicenter single-arm study enrolling consecutive STEMI patients undergoing primary percutaneous coronary intervention (pPCI) with intention-to-implant BVS. A total of 343 STEMI patients were screened during 15 months enrollment period, and 70 patients (mean age 58.6±10.3 and 74% males) fulfilled entry criteria and BVS was successfully implanted in 96% of them. All patients were invited for clinical and computed tomographic angiographie control 1 year after BVS implantation. Restenosis was defined as ≥75% area stenosis within the scaffolded segment. Three events were potentially related to BVS: 1 in-stent restenosis (treated 7 months after pPCI with drug-eluting balloon), 1 stent thrombosis (treated 2 weeks after pPCI by balloon dilatation--this patient stopped all medications after pPCI), and 1 sudden death at home 9 months after pPCI. Four other patients had events definitely unrelated to BVS. Overall, 1-year mortality was 2.9%. Computed tomographic angiography after 1 year was performed in 59 patients. All BVS were widely patent, and binary restenosis rate was 2% (the only restenosis mentioned above). Mean in-scaffold minimal luminal area was 7.8±2.6 mm², area stenosis was 20.1±16.3%, minimal luminal diameter was 3.0±0.6 mm, and diameter stenosis was 12.8±11.1%. Conclusions--BVS implantation in STEMI is feasible and safe and offers excellent 1-year clinical and angiographic outcomes. [ABSTRACT FROM AUTHOR]

This prospective, randomized, open-label multicenter trial evaluated the efficacy of catheter-based renal denervation (Symplicity, Medtronic) versus intensified pharmacological treatment including spironolactone (if tolerated) in patients with true-resistant hypertension. This was confirmed by 24-hour ambulatory blood pressure monitoring after excluding secondary hypertension and confirmation of adherence to therapy by measurement of plasma antihypertensive drug levels before enrollment. One-hundred six patients were randomized to renal denervation (n=52), or intensified pharmacological treatment (n=54) with baseline systolic blood pressure of 159±17 and 155±17 mm Hg and average number of drugs 5.1 and 5.4, respectively. A significant reduction in 24-hour average systolic blood pressure after 6 months (-8.6 [95% cofidence interval: -11.8, -5.3] mm Hg; P<0.001 in renal denervation versus -8.1 [95% cofidence interval: -12.7, -3.4] mm Hg; P=0.001 in pharmacological group) was observed, which was comparable in both groups. Similarly, a significant reduction in systolic office blood pressure (-12.4 [95% cofidence interval: -17.0, -7.8] mm Hg; P<0.001 in renal denervation versus -14.3 [95% cofidence interval: -19.7, -8.9] mm Hg; P<0.001 in pharmacological group) was present. Between-group differences in change were not significant. The average number of antihypertensive drugs used after 6 months was significantly higher in the pharmacological group (+0.3 drugs; P<0.001). A significant increase in serum creatinine and a parallel decrease of creatinine clearance were observed in the pharmacological group; between-group difference were borderline significant. The 6-month results of this study confirmed the safety of renal denervation. In conclusion, renal denervation achieved reduction of blood pressure comparable with intensified pharmacotherapy. [ABSTRACT FROM AUTHOR]

Objectives The purpose of this study was to compare the 1-year outcome between bioresorbable vascular scaffold (BVS) and everolimus-eluting metallic stent (EES) in ST-segment elevation myocardial infarction (STEMI) patients. Background The Absorb BVS (Abbott Vascular, Santa Clara, California) is a polymeric scaffold approved for treatment of stable coronary lesions. Limited and not randomized data are available on its use in ST-segment elevation myocardial infarction (STEMI) patients. Methods This study included 290 consecutive STEMI patients treated by BVS, compared with either 290 STEMI patients treated with EES or 290 STEMI patients treated with bare-metal stents (BMS) from the EXAMINATION (A Clinical Evaluation of Everolimus Eluting Coronary Stents in the Treatment of Patients With ST-segment Elevation Myocardial Infarction) trial, by applying propensity score matching. The primary endpoint was a device-oriented endpoint (DOCE), including cardiac death, target vessel myocardial infarction, and target lesion revascularization, at 1-year follow-up. Device thrombosis, according to the Academic Research Consortium criteria, was also evaluated. Results The cumulative incidence of DOCE did not differ between the BVS and EES or BMS groups either at 30 days (3.1% vs. 2.4%, hazard ratio [HR]: 1.31 [95% confidence interval (CI): 0.48 to 3.52], p = 0.593; vs. 2.8%, HR: 1.15 [95% CI: 0.44 to 2.30], p = 0.776, respectively) or at 1 year (4.1% vs. 4.1%, HR: 0.99 [95% CI: 0.23 to 4.32], p = 0.994; vs. 5.9%, HR: 0.50 [95% CI: 0.13 to 1.88], p = 0.306, respectively). Definite/probable BVS thrombosis rate was numerically higher either at 30 days (2.1% vs. 0.3%, p = 0.059; vs. 1.0%, p = 0.324, respectively) or at 1 year (2.4% vs. 1.4%, p = 0.948; vs. 1.7%, p = 0.825, respectively), as compared with EES or BMS. Conclusions At 1-year follow-up, STEMI patients treated with BVS showed similar rates of DOCE compared with STEMI patients treated with EES or BMS, although rate of scaffolds thrombosis, mostly clustered in the early phase, was not negligible. Larger studies with longer follow-up are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Abstract: This article highlights the difficulties posed by initial radiological investigations that misleadingly interpreted a linear opacity in the ascending colon of a 2-year-old to be a complicating calcified Ascaris. Final surgical management revealed an unusual cause for the tram tracking effect so pathognomonic of Ascaris infestation. Of interest are the images of the abdominal x-ray, ultrasound scan, and barium study. [Copyright &y& Elsevier]

An abstract of the article "Predictive value of surface ECG on amount of myocardium with preserved perfusion in patients after Q-wave myocardial infarction: echo-contrast study" by P. Tousek and colleagues is presented.

An abstract of the article "Evaluation of Prognostic Important Segments by Real-Time Contrast Echocardiography in Successfully Treated Patients with the First Myocardial Infarction" by J. Krupicka and colleagues is presented.

Background: The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied.Methods: In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority.Results: A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P = 0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P = 0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, -8.2 percentage points; 95% CI for noninferiority, -14.9 to -1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P = 0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, -0.2 percentage points; 95% CI for noninferiority, -4.7 to 4.3; P = 0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P = 0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial.Conclusions: Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.). [ABSTRACT FROM AUTHOR]

Background: The roles of anticoagulation alone or with an antiplatelet agent after transcatheter aortic-valve implantation (TAVI) have not been well studied.Methods: We performed a randomized trial of clopidogrel in patients undergoing TAVI who were receiving oral anticoagulation for appropriate indications. Patients were assigned before TAVI in a 1:1 ratio not to receive clopidogrel or to receive clopidogrel for 3 months. The two primary outcomes were all bleeding and non-procedure-related bleeding over a period of 12 months. Procedure-related bleeding was defined as Bleeding Academic Research Consortium type 4 severe bleeding, and therefore most bleeding at the puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction at 12 months (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2), both tested for noninferiority (noninferiority margin, 7.5 percentage points) and superiority.Results: Bleeding occurred in 34 of the 157 patients (21.7%) receiving oral anticoagulation alone and in 54 of the 156 (34.6%) receiving oral anticoagulation plus clopidogrel (risk ratio, 0.63; 95% confidence interval [CI], 0.43 to 0.90; P = 0.01); most bleeding events were at the TAVI access site. Non-procedure-related bleeding occurred in 34 patients (21.7%) and in 53 (34.0%), respectively (risk ratio, 0.64; 95% CI, 0.44 to 0.92; P = 0.02). Most bleeding occurred in the first month and was minor. A secondary composite 1 event occurred in 49 patients (31.2%) receiving oral anticoagulation alone and in 71 (45.5%) receiving oral anticoagulation plus clopidogrel (difference, -14.3 percentage points; 95% CI for noninferiority, -25.0 to -3.6; risk ratio, 0.69; 95% CI for superiority, 0.51 to 0.92). A secondary composite 2 event occurred in 21 patients (13.4%) and in 27 (17.3%), respectively (difference, -3.9 percentage points; 95% CI for noninferiority, -11.9 to 4.0; risk ratio, 0.77; 95% CI for superiority, 0.46 to 1.31).Conclusions: In patients undergoing TAVI who were receiving oral anticoagulation, the incidence of serious bleeding over a period of 1 month or 1 year was lower with oral anticoagulation alone than with oral anticoagulation plus clopidogrel. (Funded by the Netherlands Organization for Health Research and Development; POPular TAVI EU Clinical Trials Register number, 2013-003125-28; ClinicalTrials.gov number, NCT02247128.). [ABSTRACT FROM AUTHOR]

Introduction: Observational studies have shown low bleeding rates in patients with atrial fibrillation (AF) treated by left atrial appendage closure (LAAC); however, data from randomized studies are lacking. This study compared bleeding events among patients with AF treated by LAAC and nonvitamin K anticoagulants (NOAC)., Methods: The Prague-17 trial was a prospective, multicenter, randomized trial that compared LAAC to NOAC in high-risk AF patients. The primary endpoint was a composite of a cardioembolic event, cardiovascular death, and major and clinically relevant nonmajor bleeding (CRNMB) defined according to the International Society on Thrombosis and Hemostasis (ISTH)., Results: The trial enrolled 402 patients (201 per arm), and the median follow-up was 3.5 (IQR 2.6-4.2) years. Bleeding occurred in 24 patients (29 events) and 32 patients (40 events) in the LAAC and NOAC groups, respectively. Six of the LAAC bleeding events were procedure/device-related. In the primary intention-to-treat analysis, LAAC was associated with similar rates of ISTH major or CRNMB (sHR 0.75, 95% CI 0.44-1.27, p = 0.28), but with a reduction in nonprocedural major or CRNMB (sHR 0.55, 95% CI 0.31-0.97, p = 0.039). This reduction for nonprocedural bleeding with LAAC was mainly driven by a reduced rate of CRNMB (sHR for major bleeding 0.69, 95% CI 0.34-1.39, p = .30; sHR for CRNMB 0.43, 95% CI 0.18-1.03, p = 0.059). History of bleeding was a predictor of bleeding during follow-up. Gastrointestinal bleeding was the most common bleeding site in both groups., Conclusion: During the 4-year follow-up, LAAC was associated with less nonprocedural bleeding. The reduction is mainly driven by a decrease in CRNMB., (© 2023 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

This study examined the prevalence of acute and chronic myocardial injury according to standard criteria in patients after acute ischaemic stroke (AIS) and its relation to stroke severity and short-term prognosis. Between August 2020 and August 2022, 217 consecutive patients with AIS were enrolled. Plasma levels of high-sensitive cardiac troponin I (hs-cTnI) were measured in blood samples obtained at the time of admission and 24 and 48 h later. The patients were divided into three groups according to the Fourth Universal Definition of Myocardial Infarction: no injury, chronic injury, and acute injury. Twelve-lead ECGs were obtained at the time of admission, 24 and 48 h later, and on the day of hospital discharge. A standard echocardiographic examination was performed within the first 7 days of hospitalization in patients with suspected abnormalities of left ventricular function and regional wall motion. Demographic characteristics, clinical data, functional outcomes, and all-cause mortality were compared between the three groups. The National Institutes of Health Stroke Scale (NIHSS) at the time of admission and the modified Rankin Scale (mRS) 90 days following hospital discharge were used to assess stroke severity and outcome. Elevated hs-cTnI levels were measured in 59 patients (27.2%): 34 patients (15.7%) had acute myocardial injury and 25 patients (11.5%) had chronic myocardial injury within the acute phase after ischaemic stroke. An unfavourable outcome, evaluated based on the mRS at 90 days, was associated with both acute and chronic myocardial injury. Myocardial injury was also strongly associated with all-cause death, with the strongest association in patients with acute myocardial injury, at 30 days and at 90 days. Kaplan-Meier survival curves showed that all-cause mortality was significantly higher in patients with acute and chronic myocardial injury than in patients without myocardial injury ( P < 0.001). Stroke severity, evaluated with the NIHSS, was also associated with acute and chronic myocardial injury. A comparison of the ECG findings between patients with and without myocardial injury showed a higher occurrence in the former of T-wave inversion, ST segment depression, and QTc prolongation. In echocardiographic analysis, a new abnormality in regional wall motion of the left ventricle was identified in six patients. Chronic and acute myocardial injury with hs-cTnI elevation after AIS are associated with stroke severity, unfavourable functional outcome, and short-term mortality., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Competing Interests: Conflict of interest: None declared.

A unique clinical feature of Takotsubo syndrome (TTS) is the stress trigger factor. Different types of triggers exist, generally divided into emotional and physical stressor. The aim was to create long-term registry of all consecutive patients with TTS across all disciplines in our large university hospital. We enrolled patients on the basis of meeting the diagnostic criteria of the international InterTAK Registry. We aimed to determine type of triggers, clinical characteristics, and outcome of TTS patients during 10 years period. In our prospective, academic, single centre registry, we enrolled 155 consecutive patients with diagnoses of TTS between October 2013 and October 2022. The patients were divided into three groups, those having unknown ( n = 32; 20.6%), emotional ( n = 42; 27.1%), or physical ( n = 81; 52.3%) triggers. Clinical characteristics, cardiac enzyme levels, echocardiographic findings, including ejection fraction, and TTS type did not differ among the groups. Chest pain was less common in the group of patients with a physical trigger. On the other hand, arrhythmogenic disorders such as prolonged QT intervals, cardiac arrest requiring defibrillation, and atrial fibrillation were more common among the TTS patients with unknown triggers compared with the other groups. The highest in-hospital mortality was observed between patients having physical trigger (16% vs. 3.1% in TTS with emotional trigger and 4.8% in TTS with unknown trigger; P = 0.060). Conclusion: More than half of the patients with TTS diagnosed in a large university hospital had a physical trigger as a stress factor. An essential part of caring for these types of patients is the correct identification of TTS in the context of severe other conditions and the absence of typical cardiac symptoms. Patients with physical trigger have a significantly higher risk of acute heart complications. Interdisciplinary cooperation is essential in the treatment of patients with this diagnosis., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Recent studies have suggested a pathogenetic link between impaired mitochondria and Takotsubo syndrome (TTS), which is closely connected with catecholamine overstimulation, poor outcomes, and changes in lipid metabolism. We investigated the changes in lipid metabolism at the level of fatty acid β-oxidation and changes in the intracellular lipidomic spectrum. The immortalized cell line of HL-1 cardiomyocytes was used in this study as an established in vitro model of TTS. The cells were exposed to the non-selective β-agonist isoprenaline (ISO) for acute (2 h) and prolonged (24 h) periods. We investigated the impact on mitochondrial adenosine 5'-triphosphate (ATP) production and β-oxidation using real-time cell metabolic analysis, total lipid content, and changes in the lipidomic spectrum using high-performance liquid chromatography (HPLC) and mass spectrometry. Furthermore, modifications of selected lipid transporters were determined using real-time - polymerase chain reaction (RT-PCR) and/or Western blot techniques. By choosing this wide range of targets, we provide a detailed overview of molecular changes in lipid metabolism during catecholamine overstimulation. The present study demonstrates that acute exposure to ISO decreased ATP production by up to 42.2%, and prolonged exposure to ISO decreased β-oxidation by 86.4%. Prolonged exposure to ISO also increased lipid accumulation by 4%. Lipid spectrum analysis of prolonged exposure to ISO showed a reduced concentration of cardioprotective and an increased concentration of lipotoxic lipid molecules during long-term exposure. Decreased lipid utilization can lead to higher intracellular lipid accumulation and the formation of lipotoxic molecules. Changes in the lipid spectrum can induce pathophysiological signaling pathways leading to cardiomyocyte remodeling or apoptosis. Thus, changes in lipid metabolism induced by excessive doses of catecholamines may cause TTS and contribute to a progression of heart failure, which is at increased risk after a TTS episode., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Fiserova, Trinh, Elkalaf, Vacek, Heide, Martinkova, Bechynska, Kosek, Hajslova, Fiser, Tousek and Polak.)

Background: To assess whether hypoxia, as can be found in obstructive sleep apnea syndrome, is causally associated with the development of heart failure through a direct effect on calcium leakage from the sarcoplasmic reticulum., Methods: The impact of hypoxia on sarcoplasmic reticulum calcium leakage and expres- sion of RyR2 (ryanodine receptor2) and SERC2a (sarcoplasmic reticulum Ca2+ATPase 2a) was investigated together with the outcomes of JTV-519 and S107 treatment. HL-1 car- diomyocytes were cultured for 7 days on gas-permeable cultureware under control (12% O2) or hypoxic (1% O2) conditions with or without JTV-519 or S107. SRCL was assessed using a Fluo-5N probe. Gene and protein expression was analyzed using qPCR and western blotting., Results: Hypoxic exposure increased sarcoplasmic reticulum calcium leakage by 39% and reduced RyR2 gene expression by 52%. No effect on RyR2 protein expression was observed. Treatment with 1μM JTV-519 reduced sarcoplasmic reticulum calcium leakage by 52% and 35% under control and hypoxic conditions, respectively. Administration of 1 μM JTV-519 increased RyR2 gene expression by 89% in control conditions. No effect on SRCL, RyR2, or SERC2a gene, or protein expression was observed with S107 treatment., Conclusion: Hypoxia increased sarcoplasmic reticulum calcium leakage which was ame- liorated by JTV-519 treatment independently of gene or protein expression. JTV-519 rep- resents a possible treatment for obstructive sleep apnea-associated HF.

Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to be associated with poor prognosis after cardiovascular events. We aimed to assess the dynamic changes in TRAIL levels and the relation of TRAIL level to stroke severity, its impact on the short-term outcomes, and its association with markers of cardiac injury in patients after acute stroke., Methods: Between August 2020 and August 2021, 120 consecutive patients, 104 after acute ischemic stroke (AIS), 76 receiving reperfusion therapy, and 16 patients after intracerebral hemorrhage (ICH) were enrolled in our study. Blood samples were obtained from patients at the time of admission, 24 h later, and 48 h later to determine the plasma level of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and high-sensitive Troponin I (hs-TnI). Twelve-lead ECGs were obtained at the time of admission, 24 h later, 48 h later, and at the release of the patients. Evaluations were performed using the National Institutes of Health Stroke Scale (NIHSS) at the time of admission and using the modified Rankin Scale (mRS) 90 days following the patient's discharge from the hospital., Results: We observed a connection between lower TRAIL levels and stroke severity evaluated using the NIHSS ( p = 0.044) on the first day. Lower TRAIL showed an association with severe disability and death as evaluated using the mRS at 90 days, both after 24 ( p = 0.0022) and 48 h ( p = 0.044) of hospitalization. Moreover, we observed an association between lower TRAIL and NT-proBNP elevation at the time of admission ( p = 0.039), after 24 ( p = 0.043), and after 48 h ( p = 0.023) of hospitalization. In the ECG analysis, lower TRAIL levels were associated with the occurrence of premature ventricular extrasystoles ( p = 0.043), and there was an association with prolonged QTc interval ( p = 0.052)., Conclusions: The results show that lower TRAIL is associated with stroke severity, unfavorable functional outcome, and short-term mortality in patients after acute ischemic stroke. Moreover, we described the association with markers of cardiac injury and ECG changes.

Background: Minimally invasive aortic valve replacement via upper partial sternotomy (MiniAVR) provides very good short-term results and delivers certain advantages in the postoperative course. There is limited data regarding the mid-term mortality and morbidity following this minimally invasive surgery., Methods: We provide a retrospective analysis of the patients, undergoing MiniAVR versus full sternotomy (FS) for aortic valve replacement with biological prosthesis. As the primary combined end-point the combination of death, stroke, and rehospitalization within 3 years postoperatively was defined. Data have been collected from National Cardiac Surgery Registry and insurance companies., Results: Two hundred consecutive patients with aortic valve replacement (100 ministernotomy in MiniAVR group and 100 full sternotomy in FS group) with biological prosthesis were included in this study. Ministernotomy had longer cross-clamp and bypass times (median difference 6.5 min, P=0.005, and 8.5 min, P=0.002 respectively). Patients operated via upper partial sternotomy had a lower postoperative bleeding [300 mL (IQR, 290) vs. 365 mL (IQR, 207), P=0.031]. There was no difference in the 3-year mortality (14% vs. 11%, P=0.485). The mean number of readmission 3 years after surgery per capita was almost the same in both groups (1.65 vs. 1.60, P=0.836). Median time to the first readmission was longer in the MiniAVR group (difference 8.9 months). The incidence of combined end-point during 3 years postoperatively in both groups was not statistically different (P=0.148), as well as readmissions from cardio-vascular reasons (subhazard ratio 0.90, P=0.693)., Conclusions: Upper partial sternotomy can be performed safely for aortic valve replacement, without increased risk of death, stroke or re-admission in 3 years postoperatively., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1494/coif). PT reports that he is supported by the scientific grant program of the Charles University Prague, Czech Republic (UNCE MED 02 and PROGRES Q38) and in the past received a part-time salary for lectures and presentations for the firms, Medtronic, B Braun and Abiomed. The other authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Long-term follow-up after primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI) beyond 5 years is poorly described. There are no risk-stratification systems available for routine use. This retrospective, academic, two-centre analysis included consecutive patients who presented with acute STEMI between March 2008 and December 2019. In total, 5263 patients underwent pPCI; all patients were included in the analysis only once. Baseline characteristics were gathered from prospective local registries and based on initial hospitalization. The study enrolled 5263 patients who had been treated with pPCI; it found that cardiovascular mortality was the most frequent cause of death (65.0%) on long-term follow-up to 12 years. Myocardial infarction associated mortality was 27.2%. Cardiovascular mortality was dominant, including in the landmark analysis beyond 1 year. Multivariate analysis identified significant predictors for long-term cardiovascular mortality: age, history of diabetes mellitus, history of renal insufficiency, history of heart failure, Killip class, and successful pPCI at presentation. A predictive model was built to evaluate the risk of cardiovascular death with a high discrimination value (C-statistic = 0.84). Cardiovascular diseases remain the leading cause of long-term mortality after pPCI in the Central European population. Our novel predictive model provides risk stratification; it could identify patients who would experience the greatest benefit from aggressive secondary prevention measures., (Published on behalf of the European Society of Cardiology. © The Author(s) 2022.)

We describe the internal structure, spatial organization and dynamic formation of coronary artery thrombi from ST-segment elevation myocardial infarction patients. Scanning electron microscopy (SEM) revealed significant differences among four groups of patients (<2 hours; 2-6 hours; 6-12 hours, and >12 hours) related to the time of ischemia. Coronary artery thrombi from patients presenting less than 2 hours after the infarction were almost entirely composed of platelets, with small amounts of fibrin and red blood cells. In contrast, thrombi from late presenters (>12 hours) consisted of mainly platelets at the distal end, where clotting was initiated, with almost no platelets at the proximal end, while the red blood cell content went from low at the initiating end to more than 90% at the proximal end. Furthermore, fibrin was present mainly on the outside of the thrombi and older thrombi contained thicker fibers. The red blood cells in late thrombi were compressed to a close-packed, tessellated array of polyhedral structures, called polyhedrocytes. Moreover, there was redistribution from the originally homogeneous composition to fibrin and platelets to the outside, with polyhedrocytes on the interior. The presence of polyhedrocytes and the redistribution of components are signs of in vivo clot contraction (or retraction). These results suggest why later thrombi are resistant to fibrinolytic agents and other treatment modalities, since the close-packed polyhedrocytes form a nearly impermeable seal. Furthermore, it is of particular clinical significance that these findings suggest specific disparate therapies that will be most effective at different stages of thrombus development., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: The PRAGUE-17 (Left Atrial Appendage Closure vs Novel Anticoagulation Agents in Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) was noninferior to nonwarfarin direct oral anticoagulants (DOACs) for preventing major neurological, cardiovascular, or bleeding events in patients with atrial fibrillation (AF) who were at high risk., Objectives: This study sought to assess the prespecified long-term (4-year) outcomes in PRAGUE-17., Methods: PRAGUE-17 was a randomized noninferiority trial comparing percutaneous LAAC (Watchman or Amulet) with DOACs (95% apixaban) in patients with nonvalvular AF and with a history of cardioembolism, clinically-relevant bleeding, or both CHA 2 DS 2 -VASc ≥3 and HASBLED ≥2. The primary endpoint was a composite of cardioembolic events (stroke, transient ischemic attack, or systemic embolism), cardiovascular death, clinically relevant bleeding, or procedure-/device-related complications (LAAC group only). The primary analysis was modified intention-to-treat., Results: This study randomized 402 patients with AF (201 per group, age 73.3 ± 7.0 years, 65.7% male, CHA 2 DS 2 -VASc 4.7 ±1.5, HASBLED 3.1 ± 0.9). After 3.5 years median follow-up (1,354 patient-years), LAAC was noninferior to DOACs for the primary endpoint by modified intention-to-treat (subdistribution HR [sHR]: 0.81; 95% CI: 0.56-1.18; P = 0.27; P for noninferiority = 0.006). For the components of the composite endpoint, the corresponding sHRs were 0.68 (95% CI: 0.39-1.20; P = 0.19) for cardiovascular death, 1.14 (95% CI: 0.56-2.30; P = 0.72) for all-stroke/transient ischemic attack, 0.75 (95% CI: 0.44-1.27; P = 0.28) for clinically relevant bleeding, and 0.55 (95% CI: 0.31-0.97; P = 0.039) for nonprocedural clinically relevant bleeding. The primary endpoint outcomes were similar in the per-protocol (sHR: 0.80; 95% CI: 0.54-1.18; P = 0.25) and on-treatment (sHR: 0.82; 95% CI: 0.56-1.20; P = 0.30) analyses., Conclusions: In long-term follow-up of PRAGUE-17, LAAC remains noninferior to DOACs for preventing major cardiovascular, neurological, or bleeding events. Furthermore, nonprocedural bleeding was significantly reduced with LAAC. (PRAGUE-17 [Left Atrial Appendage Closure vs Novel Anticoagulation Agents in Atrial Fibrillation]; NCT02426944)., Competing Interests: Funding Support and Author Disclosures This work was supported by a research grant AZV 15-29565A from the Ministry of Health, Czech Republic. Dr Osmancik has received occasional speaking honoraria from Bayer and Abbott. Dr Taborsky has served on Advisory Boards for Bayer and Pfizer. Dr Kala has served on an Advisory Board and Speakers Bureau for Bayer; has served on an Advisory Board for Boston Scientific; and has received consulting fees from Boston Scientific. Dr Poloczek has received speaking honoraria from Abbott. Dr Haman has received speaking honoraria from Pfizer. Dr Zemanek has received speaking honoraria from Abbott and Bayer. Dr Peichl has received occasional speaking honoraria from Abbott; and has received consulting fees from Abbott, Biotronik, and Medtronic. Dr Havranek has received speaking honoraria from Boehringer Ingelheim; and has served on an Advisory Board for Boehringer Ingelheim. Dr Widimsky has received occasional honoraria from Bayer, Pfizer, and Boehringer Ingelheim. Dr Reddy has received consulting income and grant support from Abbott Inc and Boston Scientific Inc; unrelated to this manuscript, he has also served as a consultant for Ablacon, Acutus Medical, Affera, Apama Medical, APN Health, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, Biosense Webster, BioTel Heart, Biotronik, Cardiac Implants, CardiaCare, Cardiofocus, Cardionomic, CardioNXT/AFTx, Circa Scientific, CoreMap, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EBR, EPD, Epix Therapeutics, EpiEP, Eximo, Farapulse, Fire1, Gore and Associates, HRT, Impulse Dynamics, Intershunt, Javelin, Kardium, Keystone Heart, LuxMed, Medlumics, Medtronic, Middlepeak, Nuvera, Philips, Pulse Biosciences, Sirona Medical, and Valcare Vizaramed; and owns equity in Ablacon, Acutus Medical, Affera, Apama Medical, APN Health, Aquaheart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, Cardiac Implants, CardiaCare, CardioNXT/AFTx, Circa Scientific, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD, Epix Therapeutics, EpiEP, Eximo, Farapulse, Fire1, HRT, Intershunt, Javelin, Kardium, Keystone Heart, LuxMed, Manual Surgical Sciences, Medlumics, Middlepeak, Newpace, Nuvera, Pulse Biosciences, Sirona Medical, Surecor, Valcare, and Vizaramed. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The cardiovascular system is markedly affected by stress after stroke. There is a complex interaction between the brain and heart, and the understanding of the mutual effects has increased in recent decades. Stroke is accompanied by pathological disturbances leading to autonomic dysfunction and systemic inflammation, which leads to changes in cardiomyocyte metabolism. Cardiac injury after stroke may lead to serious complications and long-term cardiac problems. Evidence suggests that blood biomarkers and electrocardiogram analyses can be valuable for estimating the severity, prognosis, and therapy strategy in patients after stroke. It is necessary to distinguish whether these abnormalities presenting in stroke patients are caused by coexisting ischemic heart disease or are caused by brain injury directly. Distinguishing the origin can have a great impact on the treatment of patients after acute stroke. In this article, we focus on epidemiology, pathophysiological mechanisms, and the presentation of cardiac changes in patients after stroke.

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.