Aims The EURO-ENDO registry aimed to study the management and outcomes of patients with infective endocarditis (IE). Methods and results Prospective cohort of 3116 adult patients (2470 from Europe, 646 from non-ESC countries), admitted to 156 hospitals in 40 countries between January 2016 and March 2018 with a diagnosis of IE based on ESC 2015 diagnostic criteria. Clinical, biological, microbiological, and imaging [echocardiography, computed tomography (CT) scan, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT)] data were collected. Infective endocarditis was native (NVE) in 1764 (56.6%) patients, prosthetic (PVIE) in 939 (30.1%), and device-related (CDRIE) in 308 (9.9%). Infective endocarditis was community-acquired in 2046 (65.66%) patients. Microorganisms involved were staphylococci in 1085 (44.1%) patients, oral streptococci in 304 (12.3%), enterococci in 390 (15.8%), and Streptococcus gallolyticus in 162 (6.6%). 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed in 518 (16.6%) patients and presented with cardiac uptake (major criterion) in 222 (42.9%) patients, with a better sensitivity in PVIE (66.8%) than in NVE (28.0%) and CDRIE (16.3%). Embolic events occurred in 20.6% of patients, and were significantly associated with tricuspid or pulmonary IE, presence of a vegetation and Staphylococcus aureus IE. According to ESC guidelines, cardiac surgery was indicated in 2160 (69.3%) patients, but finally performed in only 1596 (73.9%) of them. In-hospital death occurred in 532 (17.1%) patients and was more frequent in PVIE. Independent predictors of mortality were Charlson index, creatinine > 2 mg/dL, congestive heart failure, vegetation length > 10 mm, cerebral complications, abscess, and failure to undertake surgery when indicated. Conclusion Infective endocarditis is still a life-threatening disease with frequent lethal outcome despite profound changes in its clinical, microbiological, imaging, and therapeutic profiles.

AimTo evaluate the long-term outcome of patients with Takotsubo syndrome (TTS) and severely reduced left ventricular ejection fraction (LVEF ≤ The study population included 326 patients (mean age 69.5 ± 10.7 years, 28 male) with TTS enrolled in the Takotsubo Italian Network, divided into two groups according to LVEF (≤ 35%, n = 131; > 35%, n = 195), as assessed by transthoracic echocardiography at hospital admission. In-hospital events were recorded in both groups. At long-term follow-up (median 26.5 months, interquartile range 18-33), composite major adverse cardiac events (MACE: cardiac death, acute myocardial infarction, heart failure, and TTS recurrence) and rehospitalization were investigated. Compared to patients with LVEF > 35%, patients with LVEF ≤ 35% were older (71.2 ± 10.8 vs. 68.4 ± 10.6 years; P = 0.026) and experienced more frequently cardiogenic shock (16% vs. 4.6%; P < 0.001), acute heart failure (28.2% vs. 12.8%; P = 0.001), and intra-aortic balloon pump support (11.5% vs. 2.6%; P = 0.001) in the acute phase. At long-term follow-up, higher rates of composite MACE (25.2% vs. 10.8%; P = 0.001) and rehospitalization for cardiac causes (26% vs. 13.3%; P = 0.004) were observed in these patients. LVEF ≤ 35% at admission [hazard ratio (HR) 2.184, 95% confidence interval (CI) 1.231-3.872; P = 0.008] and age (HR 1.041, 95% CI 1.011-1.073; P = 0.006) were independent predictors of MACE. Patients with LVEF ≤ 35% also had a significant lower freedom from composite MACE during long-term follow-up ( 2 = 11.551, P = 0.001).

Molecular mechanisms protecting cardiomyocytes from stress-induced death, including tension stress, are essential for cardiac physiology and defects in these protective mechanisms can result in pathological alterations. Bcl2-associated athanogene 3 (BAG3) is expressed in cardiomyocytes and is a component of the chaperone-assisted autophagy pathway, essential for homeostasis of mechanically altered cells. BAG3 ablation in mice results in a lethal cardiomyopathy soon after birth and mutations of this gene have been associated with different cardiomyopathies including stress-induced Takotsubo cardiomyopathy (TTC). The pathogenic mechanism leading to TTC has not been defined, but it has been suggested that the heart can be damaged by excessive epinephrine (epi) spillover in the absence of a protective mechanism. The aim of this study was to provide more evidence for a role of BAG3 in the pathogenesis of TTC. Therefore, we sequenced BAG3 gene in 70 TTC patients and in 81 healthy donors with the absence of evaluable cardiovascular disease. Mutations and polymorphisms detected in the BAG3 gene included a frequent nucleotide change g2252c in the BAG3 3′-untranslated region (3′-UTR) of Takotsubo patients (P<0.05), resulting in loss of binding of microRNA-371a-5p (miR-371a-5p) as evidenced by dual-luciferase reporter assays and argonaute RNA-induced silencing complex catalytic component 2/pull-down assays. Moreover, we describe a novel signaling pathway in cardiomyocytes that leads to BAG3 upregulation on exposure to epi through an ERK-dependent upregulation of miR-371a-5p. In conclusion, the presence of a g2252c polymorphism in the BAG3 3′-UTR determines loss of miR-371a-5p binding and results in an altered response to epi, potentially representing a new molecular mechanism that contributes to TTC pathogenesis.

Aim The aim of this study was to assess the prognostic value of ABCDE-SE in a prospective, large scale, multicentre, international, effectiveness study. Stress echocardiography (SE) was recently upgraded to the ABCDE protocol: step A, regional wall motion abnormalities; step B, B lines; step C, left ventricular contractile reserve; step D, Doppler-based coronary flow velocity reserve in left anterior descending coronary artery; and step E, electrocardiogram-based heart rate reserve. Methods and results From July 2016 to November 2020, we enrolled 3574 all-comers (age 65 ± 11 years, 2070 males, 58%; ejection fraction 60 ± 10%) with known or suspected chronic coronary syndromes referred from 13 certified laboratories. All patients underwent clinically indicated ABCDE-SE. The employed stress modality was exercise (n = 952, with semi-supine bike, n = 887, or treadmill, n = 65 with adenosine for step D) or pharmacological stress (n = 2622, with vasodilator, n = 2151; or dobutamine, n = 471). SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). All-cause death was the only endpoint. Rate of abnormal results was 16% for A, 30% for B, 36% for C, 28% for D, and 37% for E steps. During a median follow-up of 21 months (interquartile range: 13–36), 73 deaths occurred. Global X2 was 49.5 considering clinical variables, 50.7 after step A only (P = NS (not significant)) and 80.6 after B–E steps (P &lt; 0.001 vs. step A). Annual mortality rate ranged from 0.4% person-year for score 0 up to 2.7% person-year for score 5. Conclusion ABCDE-SE allows an effective prediction of survival in patients with chronic coronary syndromes.

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Aims The aim of the present meta-analysis was to evaluate the efficacy and safety of non-vitamin K oral antagonists (NOACs) vs. vitamin K antagonists (VKAs) in elderly patients with atrial fibrillation (AF) and indirectly compare NOACs in this population. Methods and results MEDLINE, Cochrane, ISI Web of Sciences, and SCOPUS were searched for randomized or adjusted observational studies comparing NOACs vs. VKAs for stroke prevention in AF patients ≥75 years. The primary efficacy and safety outcomes of this meta-analysis were the composite of stroke and systemic embolism (SSE) and major bleedings, respectively. Other secondary outcomes were also analysed. The analysis included 22 studies enrolling 440 281 AF patients ≥ 75 years. The risk of SSE was significantly lower with NOACs vs. VKAs [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.70–0.89], whereas no differences were found for major bleedings (HR 0.94; 95% CI 0.85–1.05). NOACs reduced the risk of intracranial bleeding (HR 0.46; 95% CI 0.38–0.58), haemorrhagic stroke (HR 0.61; 95% CI 0.48–0.79) and fatal bleeding (HR 0.46; 95% CI 0.30–0.72) but increased gastrointestinal (GI) bleedings (HR 1.46; 95% CI 1.30–1.65), compared to VKAs. The adjusted indirect comparison showed no significant differences in term of SSE between NOAC agents. Conversely, the risk of major bleeding was higher for rivaroxaban vs. apixaban (HR 1.69; 95% CI 1.39–2.08) and edoxaban (HR 1.37; 95% CI 1.14–1.67), and for dabigatran vs. apixaban (HR 1.47; 95% CI 1.18–1.85). Conclusion In elderly patients with AF, NOACs are associated to a lower risk of SSE, intracranial bleeding, haemorrhagic stroke and fatal bleeding than VKAs, but increase GI bleedings. In this analysis, the safety profile of individual NOAC agents was significantly different.

Background: Left ventricular noncompaction cardiomyopathy (LVNC) is associated with poor clinical outcome in childhood. Standard diagnostic criteria are still controversial, especially in young patients. Recent studies in adults demonstrated that left ventricular (LV) twist is abnormal in LVNC, but it has not been investigated in pediatric patients to date. Our aim was to assess LV cardiac mechanics, LV twist, and the prevalence of rigid body rotation, using 2-dimensional speckle tracking echocardiography, in young patients with LVNC and LV hypertrabeculation. Methods: Forty-seven children (age range: 0–18 years) were assessed for suspected LVNC. All patients underwent 2-dimensional speckle tracking echocardiography and cardiovascular magnetic resonance imaging at 1.5 Tesla (T). Twenty-three patients fulfilled the cardiovascular magnetic resonance imaging diagnostic criteria for LVNC (LVNC group), while the remaining 24 did not and were included in the LV hypertrabeculation group. Forty-seven age- and sex-matched healthy volunteers were used as controls. Results: The average LV twist was significantly reduced in LVNC compared with control and LV hypertrabeculation. Rigid body rotation was recognized in 13 (56%) children with LVNC and in 1 (4%) child with LV hypertrabeculation and a strong family history for LVNC. Multivariable analysis demonstrated that LV twist is an independent predictor of LVNC ( P =0.006; coefficient=0.462). The receiver operating characteristics curve showed that LV twist had optimal predictive value to discriminate patients with LVNC (cutoff value <5.8°; sensitivity, 82%; specificity, 92%; area under the curve=0.914). Conclusions: LV twist has good predictive value in diagnosing LVNC in young patients. Our findings strongly support the routine use of 2-dimensional speckle tracking echocardiography in the evaluation of young patients with suspected LVNC.