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Aims To assess the proportion of patients with heart failure and reduced ejection fraction (HFrEF) who are eligible for sacubitril/valsartan (LCZ696) based on the European Medicines Agency/Food and Drug Administration (EMA/FDA) label, the PARADIGM‐HF trial and the 2016 ESC guidelines, and the association between eligibility and outcomes. Methods and results Outpatients with HFrEF in the ESC‐EORP‐HFA Long‐Term Heart Failure (HF‐LT) Registry between March 2011 and November 2013 were considered. Criteria for LCZ696 based on EMA/FDA label, PARADIGM‐HF and ESC guidelines were applied. Of 5443 patients, 2197 and 2373 had complete information for trial and guideline eligibility assessment, and 84%, 12% and 12% met EMA/FDA label, PARADIGM‐HF and guideline criteria, respectively. Absent PARADIGM‐HF criteria were low natriuretic peptides (21%), hyperkalemia (4%), hypotension (7%) and sub‐optimal pharmacotherapy (74%); absent Guidelines criteria were LVEF>35% (23%), insufficient NP levels (30%) and sub‐optimal pharmacotherapy (82%); absent label criteria were absence of symptoms (New York Heart Association class I). When a daily requirement of ACEi/ARB ≥ 10 mg enalapril (instead of ≥ 20 mg) was used, eligibility rose from 12% to 28% based on both PARADIGM‐HF and guidelines. One‐year heart failure hospitalization was higher (12% and 17% vs. 12%) and all‐cause mortality lower (5.3% and 6.5% vs. 7.7%) in registry eligible patients compared to the enalapril arm of PARADIGM‐HF. Conclusions Among outpatients with HFrEF in the ESC‐EORP‐HFA HF‐LT Registry, 84% met label criteria, while only 12% and 28% met PARADIGM‐HF and guideline criteria for LCZ696 if requiring ≥ 20 mg and ≥ 10 mg enalapril, respectively. Registry patients eligible for LCZ696 had greater heart failure hospitalization but lower mortality rates than the PARADIGM‐HF enalapril group.

Pain is one of the main problems for modern society and medicine, being the most common symptom described by almost all patients. When pain becomes chronic, the life of the patients is dramatically affected, being associated with significant emotional distress and/or functional disability. A complex biopsychosocial evaluation is necessary to better understand chronic pain, where good results can be obtained through interconnected biological, psychological, and social factors. The aim of this study was to find the most relevant articles existent in the PubMed database, one of the most comprehensive databases for medical literature, comprising dietary patterns to alleviate chronic pain. Through a combined search using the keywords “chronic pain” and “diet” limited to the last 10 years we obtained 272 results containing the types of diets used for chronic pain published in the PubMed database. Besides classical and alternative methods of treatment described in literature, it was observed that different diets are also a valid solution, due to many components with antioxidant and anti-inflammatory qualities capable to influence chronic pain and to improve the quality of life. Thirty-eight clinical studies and randomized controlled trials are analyzed, in an attempt to characterize present-day dietary patterns and interventions to alleviate chronic pain.

Cardiovascular (CV) engagement in coronavirus disease 2019 (COVID‐19) is a huge determinant of prognosis during the acute phase of the disease. However, little is known about the potential chronic implications of the late phase of COVID‐19 and about the appropriate approach to these patients. Heart failure, type 1 and type 2 myocardial infarction, arrhythmias, myocarditis, pulmonary fibrosis, and thrombosis have been shown to be related to severe acute respiratory syndrome coronavirus 2 infection, and a ‘long COVID‐19’ illness has been recognized with fatigue, chest pain, and dyspnoea among the most frequent symptoms reported after discharge from hospital. This paper focuses on some open questions that cardiologists are going to face during the next months in a general cardiology outpatient clinic, in particular how to evaluate a ‘post‐COVID’ patient during follow‐up of CV complications of the acute phase and how to manage new CV symptoms that could be the consequence, at least in part, of heart/vessels and/or lung involvement of the previous virus infection. Present symptoms and signs, history of previous CV disease (both preceding COVID‐19 and occurring during viral infection), and specific laboratory and imaging measurements during the acute phase may be of interest in focusing on how to approach the clinical evaluation of a post‐COVID patient and how to integrate in our standard of care the new information on COVID‐19, possibly in a multidisciplinary view. Dealing with the increased COVID‐associated CV risk burden and becoming acquainted with potential new e‐cardiology approaches aimed at integrating the cardiology practice are relevant new challenges brought by severe acute respiratory syndrome coronavirus 2 infection and its sequelae.

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.

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In this study, we tried to compare the efficacy and safety of betaxolol vs. metoprolol immediately postoperatively in coronary artery bypass grafting (CABG) patients and to determine whether prophylaxy for atrial fibrillation (AF) with betaxolol could reduce hospitalization and economic costs after cardiac surgery. Our trial was open-label, randomized, multicentric enrolling 1352 coronary surgery patients randomized to receive betaxolol or metoprolol. The primary endpoints were the composites of 30-day mortality, in-hospital AF (safety endpoints), duration of hospitalization and immobilization, quality of life, and the above endpoint plus in-hospital embolic event, bradycardia, gastrointestinal symptoms, sleep disturbances, cold extremities (efficacy plus safety endpoint). At the end of the study the incidence and probability of early postoperative AF with betaxolol was lower than with metoprolol in coronary surgery (P<0.0001). In the two study groups minor side effects were similar and no major complication was reported (P<0.001). Patient compliance was good and the general condition improved due to shortened hospitalization and immobilization with subsequent improvement in the psychological status, less arrhythmias and lack of significant side effects. In conclusion, because of its efficacy and safety, betaxolol was superior to metoprolol for the prevention of the early postoperative AF in coronary surgery.