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.

ON are a serious problem concerning long-term sequelae with major impact on activities of daily living. Further prospective evaluation is urgently needed to develop risk-adapted diagnostic strategies and preventive and interventional approaches for high-risk pts.

Background: Cardioembolic stroke (CES), generally known as the most severe subtype of ischemic stroke, is related to many factors, including diabetes mellitus (DM), hypertension (HTN), smoking, hyperlipidemia and atrial fibrillation (AF). Genetic mutations of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C have been recently associated with ischemic stroke. The purpose of this study was to analyze the prevalence of MTHFR gene polymorphisms correlated with cardiovascular risk factors in a selected population of patients with CES due to non-valvular AF (NVAF). Methods: This cross-sectional study was performed on 67 consecutive patients with acute cardioembolic stroke admitted to our hospital. The protocol included general physical examination, neurological clinical status and stroke severity evaluation, imagistic evaluation and genetic testing of MTHFRC677T and A1298C polymorphisms. Results: The prevalence of MTHFR polymorphisms in the study population was 38.2% for C677T and 40.3% for A1298C. The C677T mutation was significantly correlated with increased diastolic blood pressure (DBP) values (p = 0.007), higher total cholesterol (TC) (p = 0.003), low-density lipoprotein cholesterol (LDLc) (p = 0.003) and triglycerides (TGL) (p = 0.001), increased high-sensitive C-reactive protein (hsCRP) values (p = 0.015), HbA1c (p = 0.004) and left ventricle ejection fraction (LVEF) (p = 0.047) and lower high-density lipoprotein cholesterol (HDLc) (p < 0.001) compared to patients without this genetic variant. This genetic profile also included significantly higher CHA2DS2VASC (p = 0.029) and HASBLED (Hypertension, Abnormal liver/renal function, Stroke, Bleeding, Labile INR, Elderly age(>65 years), Drug/Alcohol usage history/Medication usage with bleeding predisposition) (p = 0.025) scores. Stroke severity in patients with MTHFRA1298C mutation was significantly increased when applying National Institutes of Health Stroke Scale (NIHSS) (p = 0.006) and modified Rankin scale (mRS) (p = 0.020) scores. The presence of A1298C mutation as a dependent variable was associated with significantly higher TGL values (odds ratio (OR) = 2.983, 95%CI = (1.972, 7.994)). Conclusions: The results obtained in this study demonstrate that MTHFR gene polymorphisms have a high prevalence in an NVAF cardioembolic stroke population. Moreover, an association between C677T mutation and stroke severity was highlighted. The C677T mutation in patients with NVAF was correlated with a higher incidence of cardiovascular comorbidities (hypertension HTN, heart failure (HF), dyslipidemia, type II diabetes mellitus (T2DM) with high HbA1c and increased inflammatory state). The A1298CMTHFR gene mutation was associated with a higher incidence of previous lacunar stroke and stroke recurrence rate, while dyslipidemia was the main cardiovascular comorbidity in this category.

Cancer treatments can have significant cardiovascular adverse effects that can cause cardiomyopathy and heart failure with reduced survival benefit and considerable decrease in the use of antineoplastic therapy. The purpose of this study is to assess the role of TLR2 and TLR4 gene expression as an early marker for the risk of doxorubicin-induced cardiomyopathy in correlation with early diastolic dysfunction in patients treated with doxorubicin. Our study included 25 consecutive patients who received treatment with doxorubicin for hematological malignancies (leukemia, lymphomas or multiple myeloma), aged 18-65 years, with a survival probability>6 months and with left ventricular ejection fraction>50%. Exclusion criteria consisted of the following: previous anthracycline therapy, previous radiotherapy, history of heart failure or chronic renal failure, atrial fibrillation, and pregnancy. In all patients, in fasting state, a blood sample was drawn for the assessment of TLR2 and TLR4 gene expression. Gene expression was assessed by quantitative reverse transcription PCR (qRT-PCR) using blood collection, RNA isolation, cDNA reverse transcription, qRT-PCR and quantification of the relative expression. At enrollment, all patients were evaluated clinically; an ECG and an echocardiography were performed. The average amount of gene expression units was 0.113 for TLR4 (range 0.059-0.753) and 0.218 for TLR2 (range 0.046-0.269). The mean mRNA extracted quantity was 113 571 ng/μl. As for the diastolic function parameters, criteria for diastolic dysfunction were present after 6 months in 16 patients (64%). In these patients, the mean values for TLR4 were 0.1198625 and for TLR2 were 0.16454 gene expression units. As for the diastolic function parameters, criteria for diastolic dysfunction were present after 6 months in 16 patients (64%). In these patients, the mean value for TLR2 was 0.30±0.19 and for TLR4 was 0.15±0.04. The corresponding values for the patients who did not develop diastolic dysfunction were 0.16±0.07 for TLR2 (P=0.01) and 0.11±0.10 for TLR4 (P=0.2). Our study suggests that TLR4 and TLR2 expression is higher in patients under doxorubicin therapy who develop diastolic dysfunction. This may suggest a predisposition to myocardial involvement, a higher sensitivity to doxorubicin cardiac effects.

INTRODUCTION Acute kidney injury (AKI) during hospitalization is associated with increased mortality in patients with acute heart failure (AHF). In 2016, the European Society of Cardiology introduced the category of heart failure (HF) with mid-range ventricular ejection fraction (HFmrEF) as a distinct category from HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). OBJECTIVES The aim of this study was to evaluate in-hospital mortality risk associated with AKI in patients with AHF, with a focus on the HFmrEF group. PATIENTS AND METHODS A total of 365 health records of patients with a primary diagnosis of acute decompensated heart failure (ADHF) were reviewed. AKI was defined according to Acute Kidney Injury Network criteria. HF was diagnosed based on Framingham criteria. Patients with ADHF were evaluated as 3 separate groups, based on ventricular ejection fraction: HFpEF (≥50%), HFmrEF (40%-49%), and HFrEF (<40%). Risk and survival analyses were conducted on de-identified data. RESULTS The AKI-associated in-hospital mortality odds ratios for HFmrEF and HFrEF groups were 4.55 (95% CI, 1.46-14.18) and 2.59 (95% CI, 1.05-6.41), respectively, with a highly significant difference between the groups (P = 0.002; Mantel-Haenszel test). The hazard ratios in the Cox proportional hazards model were 4.79 (95% CI, 1.54-14.96) and 2.94 (95% CI, 1.27-6.80) for HFmrEF and HFrEF groups, respectively. CONCLUSIONS AKI was associated with a higher risk of mortality in patients with HFmrEF when compared with those with HFrEF, suggesting a stronger prognostic impact of AKI in patients with HFmrEF.

Purpose High mortality and a limited performance of valvular surgery are typical features of infective endocarditis (IE) in octogenarians, even though surgical treatment is a major determinant of a successful outcome in IE. Methods Data from the prospective multicentre ESC EORP EURO-ENDO registry were used to assess the prognostic role of valvular surgery depending on age. Results As compared to < 80 yo patients, ≥ 80 yo had lower rates of theoretical indication for valvular surgery (49.1% vs. 60.3%, p < 0.001), of surgery performed (37.0% vs. 75.5%, p < 0.001), and a higher in-hospital (25.9% vs. 15.8%, p < 0.001) and 1-year mortality (41.3% vs. 22.2%, p < 0.001). By multivariable analysis, age per se was not predictive of 1-year mortality, but lack of surgical procedures when indicated was strongly predictive ). By propensity analysis, 304 ≥ 80 yo were matched to 608 < 80 yo patients. Propensity analysis confirmed the lower rate of indication for valvular surgery (51.3% vs. 57.2%, p = 0.031) and of surgery performed (35.3% vs. 68.4%, p < 0.0001) in ≥ 80 yo. Overall mortality remained higher in ≥ 80 yo (in-hospital: HR 1.50[1.06-2.13], p = 0.0210; 1-yr: HR 1.58[1.21-2.05], p = 0.0006), but was not different from that of < 80 yo among those who had surgery (in-hospital: 19.7% vs. 20.0%, p = 0.4236; 1-year: 27.3% vs. 25.5%, p = 0.7176). Conclusion Although mortality rates are consistently higher in ≥ 80 yo patients than in < 80 yo patients in the general population, mortality of surgery in ≥ 80 yo is similar to < 80 yo after matching patients. These results confirm the importance of a better recognition of surgical indication and of an increased performance of surgery in ≥ 80 yo patients.

Although doxorubicin (Dox) is an effective antitumor antibiotic in the anthracycline class, it often induces the undesirable side effect of cardiomyopathy leading to congestive heart failure, which limits its clinical use. The primary goal of this study is to evaluate a reliable translational method for Dox-induced cardiotoxicity (CTX) screening, aiming to identify a high-risk population and to discover new strategies to predict and investigate this phenomenon. Early identification of the presence of iron deposits and genetic and environmental triggers that predispose individuals to increased risk of Dox-induced CTX (e.g., overexpression of Toll-like receptor 4 (TLR4)) will enable the early implementation of countermeasure therapy, which will improve the patient’s chance of survival. Our cohort consisted of 25 consecutive patients with pathologically confirmed cancer undergoing Dox chemotherapy and 12 control patients. The following parameters were measured: serum TLR4 (baseline), serum transferrin (baseline and 6-week follow-up) and iron deposition (baseline and 6-week follow-up). The average number of gene expression units was 0.121 for TLR4 (range 0.051–0.801). We subsequently correlated serum TLR4 levels in our cohort with myocardial iron overload using the cardiac magnetic resonance (CMR) T2* technique, the ventricular function (% ejection fraction, %EF) and serum transferrin levels. There is a strong negative linear relationship between serum TLR4 and CMR T2* values (r =  − 0.9106, ****P < 0.0001). There is also a linear correlation (either positive or negative) with EF and transferrin; no established relationship related to the sex of the patients was found. Patients with elevated serum TLR4 at baseline also exhibited an increase in serum transferrin levels and Dox-induced left ventricular dysfunction with a decreased EF (< 50%); this phenomenon was observed in 7 of 25 patients (28%) at the 6-week follow-up. There were no significant differences or correlations based on sex. We concluded that there is a direct relationship between Dox-induced CTX (indicated by elevated serum TLR4) and the times (ms) for T2* (decreases in which correspond to immediate and rapid iron overload).

Objectives The aim of this study was to establish a correlation between prevalence and severity of erectile dysfunction (ED) and cardiovascular (CV) co-morbidities and ongoing medication and other risk factors associated with post-stroke ED. Materials and methods For 153 patients (57.04±6.54 years) with ischemic stroke, we evaluated the pre- and post-stroke prevalence of ED using the five-item International Index of Erectile Function questionnaire (IIEF5). Erectile Function questionnaire (IIEF5). Within 5 days of admission we determined the stroke site location and severity using the National Institute of Health Stroke Scale (NIHSS). The pre- and post-stroke data obtained were compared with those of 30 control non-stroke patients (52.27±8.35). Additional cardiovascular co-morbidities, medication and risk factors were asset and analyzed. Results The IIEF5 scores were much lower [median 17 interquartile range (IQR) 10–20] post stroke than pre-stroke (median 22 IQR 12–23) and lower than in control group (median 22.5 IQR 21–24). From the analysis of comorbidities and risk factors for stroke of post- stroke group and the control group, we infer that diabetes (p=0.003), hypercholesterolemia (p<0.001), and hypertension (p<0.001) were more common in patients with stroke than those in the control group. (Table 1). From the statistical analysis of data on medication use by patients, results that more patients have used ACE inhibitors, calcium antagonists, beta blocking agents, diuretics, statins, oral agents, antiplatelet and oral anticoagulants after the stoke than before, and in terms of consumption of drugs before stroke compared with the control group, differences were not significant. Lot 1 Lot 2 Lot 3 P values P values P values post-stoke patients pre-stroke patients control group [1 vs 3] [2 vs 3] [1 vs 2] No. of Patients 153 153 30 Age, mean ± SD 57.04±6.54 57.04±6.54 52.27±8.35 Pacient with ED, N (%) 127 (83%) 76 (49.67%) 9 (30%) <0.001 0.048 <0.001 Severity of ED, N (%)   Mild 74 (48.37%) 29 (18.95%) 7 (23.33%) 0.015 0.581 <0.001   Mild to moderate 1 (0.01%) 11 (7.19%) 1 (3.33%) 0.302* 0.694* 0.127*   Moderate 28 (18.30%) 21 (13.73%) 1 (3.33%) 0.052* 0.134* <0.001*   Severe 24 (15.69%) 15 (9.80%) 0 0.016* 0.136* <0.001* IIEF5 (Erectile function)   Mean ± SD 15.53±5.89 17.83±6.18 21.83±3.31 <0.001 <0.001 <0.001   Median (Q1–Q3) 17 (10–20) 22 (12–23) 22.5 (21–24) Hamilton Score   Normal 91 (59.4%) 144 (94.1%) 23 (76.6%)   Mild depression 40 (26.1%) 1 (0.6%) 5 (16.6%)   Moderate depression 11 (7.1%) 0 (0.0%) 1 (3.3%)   Severe depression 9 (5.8%) 6 (3.9%) 1 (3.3%)   Very severe depression 2 (1.3%) 2 (1.3%) 0 (0.0%) Comorbidities   Diabetes mellitus 59 (38.5%) 3 (10.0%) 0.003*   Hypercholesterolemia 104 (67.9%) 6 (20.0%) <0.001   Hypertension 121 (79.0%) 8 (26.6%) <0.001   Obesity 36 (23.5%) 6 (20.0%) 0.674   Smoking 53 (34.6%) 5 (16.6%) 0.056*   Atrial fibrillation 22 (14.3%) 2 (6.6%) 0.377*   Carotid artery stenosis 18 (11.7%) 1 (3.3%) 0.321*   Coronary hearth disease 26 (16.9%) 1 (3.3%) 0.086* Medication   ACE inhibitors 72 (47.0%) 32 (20.9%) 2 (6.6%) <0.001* 0.075* <0.001   Calcium Antagonists 49 (32.0%) 17 (11.1%) 4 (13.3%) 0.047* 0.755* <0.001   Beta-Blokers 65 (42.4%) 36 (23.5%) 3 (10.0%) 0.001* 0.142* <0.001   Diuretics 43 (28.1%) 14 (9.1%) 3 (10.0%) 0.039* >0.999* <0.001   Statins 99 (64.7%) 25 (16.3%) 4 (13.3%) <0.001* 0.791* <0.001   Oral antidiabetics 39 (25.4%) 25 (16.3%) 1 (10.0%) 0.007* 0.084* 0.442   Insulin 20 (13.0%) 15 (9.8%) 0 (0.0%) 0.048* 0.136* 0.369   Antiplatelet drugs 131 (85.6%) 14 (9.1%) 2 (6.6%) <0.001* >0.999* <0.001   Oral anticoagulants 22 (14.3%) 8 (5.2%) 0 (0.0%) 0.028* 0.357* 0.007   Antidepressants 28 (18.3%) 12 (7.84%) 2 (6.6%) 0.176* >0.999* 0.007 Conclusions The prevalence and severity of ED increase after stroke due to disruption of autonomous central structures. The depression, functional impairment, CV co-morbidities and medication used after stroke may contribute to ED.