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Data concerning the combined prognostic role of natriuretic peptide (NP) and troponin in patients with COVID-19 are lacking. The aim of the study is to evaluate the combined prognostic value of NPs and troponin in hospitalized COVID-19 patients. From March 1, 2020 to April 9, 2020, consecutive patients with COVID-19 and available data on cardiac biomarkers at admission were recruited. Patients admitted for acute coronary syndrome were excluded. Troponin levels were defined as elevated when greater than the 99 th percentile of normal values. NPs were considered elevated if above the limit for ruling in acute heart failure (HF). A total of 341 patients were included in this study, mean age 68 ± 13 years, 72% were men. During a median follow-up period of 14 days, 81 patients (24%) died. In the Cox regression analysis, patients with elevated both NPs and troponin levels had higher risk of death compared with those with normal levels of both (hazard ratio 2.94; 95% confidence interval 1.31 to 6.64; p = 0.009), and this remained significant after adjustment for age, gender, oxygen saturation, HF history, and chronic kidney disease. Interestingly, NPs provided risk stratification also in patients with normal troponin values (hazard ratio 2.86; 95% confidence interval 1.21 to 6.72; p = 0.016 with high NPs levels). These data show the combined prognostic role of troponin and NPs in COVID-19 patients. NPs value may be helpful in identifying patients with a worse prognosis among those with normal troponin values. Further, NPs' cut-point used for diagnosis of acute HF has a predictive role in patients with COVID-19., Competing Interests: Disclosures Prof Piergiuseppe Agostoni reported nonfinancial support from Menarini, Novartis, and Boehringer; grants from Daiichiò Sankyo and Bayer; and grants and nonfinancial support from Actelion outside the submitted work. Prov Pietro Ameri reported having received speaker and advisor honoraria from Novartis, AstraZeneca, Vifor, Daiichi Sankyo, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, and Merck, Sharp & Dohme and nonfinancial support from Actelion outside the submitted work. Dr Valentina Carubelli received consulting honoraria from CVie Therapeutics Limited, Servier, and Windtree Therapeutics outside the submitted work. Dr. Riccardo Maria Inciardi received speaker and advisor honoraria from Daiichi-Sankyo, Boehringer Ingelheim. Prof Sergio Leonardi reported grants and personal fees from AstraZeneca and personal fees from BMS/Pfizer, Novo Nordisk, and Chiesi outside the submitted work. Prof Carlo Mario Lombardi received speaker and advisor honoraria from Novartis and Astra Zeneca. Dr Andrea Mortara reports personal consulting honoraria from Novartis, Servier, Astra Zeneca for participation to advisory board meetings and receives grants from Novartis and Niccomo for research trials. Prof Massimo Piepoli reported having received research grants and speaking fees from Novartis, Servier, and TRX and nonfinancial support from Vifor outside the submitted work. Prof Michele Senni reported personal fees from Novartis, Abbott, Merck, Bayer, Boehringer, Vifor, and AstraZeneca outside the submitted work. Prof Marco Metra reported personal consulting honoraria from Abbott Vascular, Amgen, Bayer, Edwards Therapeutics, Servier, Vifor Pharma, and Windtree Therapeutics for participation to advisory board meetings and executive committees of clinical trials. All other authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The sodium-glucose cotransporter 2 inhibitor empagliflozin reduces the risk of cardiovascular death or heart failure hospitalization in patients with chronic heart failure, but whether empagliflozin also improves clinical outcomes when initiated in patients who are hospitalized for acute heart failure is unknown. In this double-blind trial (EMPULSE; NCT04157751 ), 530 patients with a primary diagnosis of acute de novo or decompensated chronic heart failure regardless of left ventricular ejection fraction were randomly assigned to receive empagliflozin 10 mg once daily or placebo. Patients were randomized in-hospital when clinically stable (median time from hospital admission to randomization, 3 days) and were treated for up to 90 days. The primary outcome of the trial was clinical benefit, defined as a hierarchical composite of death from any cause, number of heart failure events and time to first heart failure event, or a 5 point or greater difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score at 90 days, as assessed using a win ratio. More patients treated with empagliflozin had clinical benefit compared with placebo (stratified win ratio, 1.36; 95% confidence interval, 1.09-1.68; P = 0.0054), meeting the primary endpoint. Clinical benefit was observed for both acute de novo and decompensated chronic heart failure and was observed regardless of ejection fraction or the presence or absence of diabetes. Empagliflozin was well tolerated; serious adverse events were reported in 32.3% and 43.6% of the empagliflozin- and placebo-treated patients, respectively. These findings indicate that initiation of empagliflozin in patients hospitalized for acute heart failure is well tolerated and results in significant clinical benefit in the 90 days after starting treatment., (© 2022. The Author(s).)

The heart failure epidemic is growing and its prevention, in order to reduce associated hospital readmission rates and its clinical and economic burden, is a key issue in modern cardiovascular medicine. The present consensus document aims to provide practical evidence-based information to support the implementation of effective preventive measures. After reviewing the most common risk factors, an overview of the population attributable risks in different continents is presented, to identify potentially effective opportunities for prevention and to inform preventive strategies. Finally, potential interventions that have been proposed and have been shown to be effective in preventing HF are listed., (The article has been co-published with permission in the European Journal of Preventive Cardiology and European Journal of Heart Failure. All rights reserved. © The Author(s) 2022. The articles are identical except for minor stylistic and spelling differences in keeping with each journal’s style. Either citation can be used when citing this article.)

Elevated serum cholesterol levels, either associated or not with increased triglycerides, represent a risk of developing vascular injury, mostly leading to atherothrombosis-related diseases including myocardial infarction and stroke. Natural products have been investigated in the last few decades as they are seen to offer an alternative solution to counteract cardiometabolic risk, due to the occurrence of side effects with the use of statins, the leading drugs for treating hyperlipidemias. Red yeast rice (RYR), a monacolin K-rich natural extract, has been found to be effective in counteracting high cholesterol, being its use accompanied by consistent warnings by regulatory authorities based on the potential detrimental responses accompanying its statin-like chemical charcateristics. Here we compared the effects of RYR with those produced by bergamot polyphenolic fraction (BPF), a well-known natural extract proven to be effective in lowering both serum cholesterol and triglycerides in animals fed a hyperlipidemic diet. In particular, BPF at doses of 10 mg/Kg given orally for 30 consecutive days, counteracted the elevation of both serum LDL cholesterol (LDL-C) and triglycerides induced by the hyperlipidemic diet, an effect which was accompanied by significant reductions of malondialdehyde (MDA) and glutathione peroxidase serum levels, two biomarkers of oxidative stress. Furthermore, the activity of BPF was associated to increased HDL cholesterol (HDL-C) levels and to strong reduction of Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels which were found increased in hyperlipidemic rats. In contrast, RYR at doses of 1 and 3 mg/Kg, produced only significant reduction of LDL-C with very poor effects on triglycerides, HDL-C, glutathione peroxidase, MDA and PCSK9 expression. This indicates that while BPF and RYR both produce serum cholesterol-lowering benefits, BPF produces additional effects on triglycerides and HDL cholesterol compared to RYR at the doses used throughout the study. These additional effects of BPF appear to be related to the reduction of PCSK9 expression and to the antioxidant properties of this extract compared to RYR, thereby suggesting a more complete protection from cardiometabolic risk.

Low-dose aspirin represents the best option in the secondary prevention of coronary artery disease, but its extensive use in primary prevention is limited by the occurrence of gastric mucosal lesions and increased risk of bleeding. We investigated the safety profile of a novel sublingual aspirin formulation in 200 healthy volunteers, randomly assigned to ten ( n = 20 each) different 7-day once-daily treatment regimens. Gastric mucosal injury based on the modified Lanza score (MLS), the histopathology of gastric mucosa and the serum determination of thromboxane B 2 (TXB 2 ) and urinary 11-dehydro-TXB 2 levels were evaluated at basal as well as after 7 days of each placebo or aspirin treatment regimen. In Groups A and B (placebo-oral and sublingual, respectively), no changes in MLS and in gastric mucosal micro-vessel diameter were found at day 7. In contrast, in Groups C and D (oral standard aspirin-100 and 50 mg daily, respectively), the median MLS was significantly increased. Very few changes were found in Groups E and F (standard sublingual aspirin-100 and 50 mg, respectively). Groups G and H (oral administration of micronized collagen-cogrinded aspirin) showed gastric protection compared to Groups C and D. Moreover, Groups I and L (sublingual collagen-cogrinded aspirin-100 and 50 mg, respectively) showed a significant reduction (Group I) or total abolition (Group L) of gastric mucosal lesions and no difference compared to the standard one in serum TXB 2 and urinary 11-dehydro-TXB 2 levels. In conclusion, our data show that the new formulation leads to a better safety profile compared to standard aspirin, representing a better therapeutic option for extended use in primary and secondary prevention of cardiovascular diseases.

Aims: Recent evidence supports the occurrence of multiple hormonal and metabolic deficiency syndrome (MHDS) in chronic heart failure (CHF). However, no large observational study has unequivocally demonstrated its impact on CHF progression and outcome. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Treatment in Heart Failure) Registry has been specifically designed to test the hypothesis that MHDS affects morbidity and mortality in CHF patients., Methods and Results: The T.O.S.CA. Registry is a prospective, multicentre, observational study involving 19 Italian centres. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydropianoandrosterone sulfate, insulin resistance, and the presence of diabetes were evaluated. A MHDS was defined as the presence of ≥2 hormone deficiencies (HDs). Primary endpoint was a composite of all-cause mortality and cardiovascular hospitalizations. Four hundred and eighty heart failure patients with ejection fraction ≤45% were enrolled. MHDS or diabetes was diagnosed in 372 patients (77.5%). A total of 271 events (97 deaths and 174 cardiovascular hospitalizations) were recorded, 41% in NO-MHDS and 62% in MHDS (P < 0.001). Median follow-up was of 36 months. MHDS was independently associated with the occurrence of the primary endpoint [hazard ratio 95% (confidence interval), 1.93 (1.37-2.73), P < 0.001] and identified a group of patients with a higher mortality [2.2 (1.28-3.83), P = 0.01], with a graded relation between HDs and cumulative events (P < 0.01)., Conclusion: MHDS is common in CHF and independently associated with increased all-cause mortality and cardiovascular hospitalization, representing a promising therapeutic target., Trial Registration: ClinicalTrials.gov identifier: NCT023358017., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: An 'optimum' universally agreed exercise programme for heart failure (HF) patients has not been found. ARISTOS-HF randomized clinical trial evaluates whether combined aerobic training (AT)/resistance training (RT)/inspiratory muscle training (IMT) (ARIS) is superior to AT/RT, AT/IMT or AT in improving aerobic capacity, left ventricular dimensions, and secondary functional outcomes., Methods and Results: Eighty-eight patients of New York Heart Association II-III, left ventricular ejection fraction  ≤ 35% were randomized to an ARIS, AT/RT, AT/IMT, or AT group, exercising 3 times/week, 180 min/week for 12 weeks. Pre- and post-training, peakVO2 was evaluated with cardiopulmonary exercise testing, left ventricular dimensions using echocardiography, walking distance with the 6-min walk test (6MWT), quality of life by the Minnesota Living with HF Questionnaire (MLwHFQ), while a programme preference survey (PPS) was used. Seventy-four patients of [mean 95% (confidence interval, CI)] age 66.1 (64.3-67.9) years and peakVO2 17.3 (16.4-18.2) mL/kg/min were finally analysed. Between-group analysis showed a trend for increased peakVO2 (mL/kg/min) [mean contrasts (95% CI)] in the ARIS group [ARIS vs. AT/RT 1.71 (0.163-3.25)(.), vs. AT/IMT 1.50 (0.0152-2.99)(.), vs. AT 1.38 (-0.142 to 2.9)(.)], additional benefits in circulatory power (mL/kg/min⋅mmHg) [ARIS vs. AT/RT 376 (60.7-690)*, vs. AT/IMT 423 (121-725)*, vs. AT 345 (35.4-656)*], left ventricular end-systolic diameter (mm) [ARIS vs. AT/RT -2.11 (-3.65 to (-0.561))*, vs. AT -2.47 (-4.01 to (-0.929))**], 6MWT (m) [ARIS vs. AT/IMT 45.6 (18.3-72.9)**, vs. AT 55.2 (27.6-82.7)****], MLwHFQ [ARIS vs. AT/RT -7.79 (-11 to (-4.62))****, vs. AT -8.96 (-12.1 to (-5.84))****], and in PPS score [mean (95% CI)] [ARIS, 4.8 (4.7-5) vs. AT, 4.4 (4.2-4.7)*] [(.) P ≤ 0.1; *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001]., Conclusion: ARISTOS-HF trial recommends exercise training for 180 min/week and supports the prescription of the ARIS training regime for HF patients (Clinical Trial Registration: http://www.clinicaltrials.gov. ARISTOS-HF Clinical Trial number, NCT03013270)., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Blood pressure (BP) and hemodynamic changes occurring in the recovery phase after a single bout of exercise have not been extensively studied in coronary artery patients, despite the potential clinical implications of reducing BP through exercise. This study aimed at investigating the hemodynamic and arterial baroreflex mechanisms possibly involved in post-exercise hypotension (PEH) in patients with coronary artery disease. Methods : In 42 normotensive coronary artery patients undergone a Cardiac Rehabilitation Program, we evaluated before and after their daily exercise training session: blood pressure (BP) and heart rate (HR). In a subgroup ( n  = 29), daily BP profile was also evaluated by ambulatory BP monitoring. In those patients showing PEH ( n  = 15), we evaluated: Cardiac Output (CO), Stroke Volume (SV), total peripheral resistances (TPR), forearm (FVR) and calf (CVR) vascular resistances, and spontaneous baroreflex sensitivity (BRS). Results: After exercise TPR was significantly reduced with a similar contribution from CVR and FVR, whereas CO and SV significantly increased. BRS showed a significant reduction mainly due to a BRS decrease in response to hypertensive stimuli. Systolic BP (SBP) was significantly reduced for 12 h after the end of a single exercise session. Conclusion: These findings indicate that in coronary artery patients, the recovery phase after exercise is characterized by PEH which is mediated mainly by a generalized peripheral vasodilation and appears to influence BP behavior throughout the daily life. Finally, the cardiac component of the arterial baroreflex seems to contribute indirectly to BP reduction occurring after exercise., 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 © 2021 Iellamo, Perrone, Caminiti, Volterrani and Legramante.)

Concurrent aerobic plus resistance exercise (RAE) and high-intensity interval exercise (HIIE) are both effective at inducing post-exercise hypotension (PEH) in patients with hypertension. However, central hemodynamic changes associated with PEH in hypertensive subjects with underlying ischemic heart disease (IHD) have been poorly investigated. The study aim was to compare the acute effects produced by these two exercise modalities on left ventricular diastolic function and left atrial function. Twenty untrained male patients with a history of hypertension and IHD under stable pharmacological therapy were enrolled. Each patient underwent three exercise sessions: RAE, HIIE and a control session without exercise, each lasting 45 min. An echocardiography examination was performed before and between 30 min and 40 min from the end of the exercise sessions. Following the exercise sessions, BP values decreased in a similar way in RAE and HIIE and were unchanged after the control session. Compared to pre-session, the ratio between early filling velocity (E) and mitral annulus early diastolic velocity (E'). E/E' increased after HIIE and remained unchanged after both RAE and control sessions (between-sessions p 0.002). Peak atrial longitudinal strain (PALS) increased slightly after RAE (+1.4 ± 1.1%), decreased after HIIE (-4.6 ± 2.4%) and was unchanged after the control session (between-sessions p 0.03). Peak atrial contraction strain (PACS) was mildly increased after RAE, was reduced after HIIE and was unchanged after the control session. Atrial volume was unchanged after both exercise sessions. Left ventricular and left atrial stiffness increased significantly after HIIE, but remained unchanged after the RAE and control sessions. Stroke volume and cardiac output increased after RAE, decreased after HIIE, and were unchanged after the control session. In conclusion, single session of RAE and HIIE brought about similar PEH in hypertensive subjects with IHD, while they evoked different central hemodynamic adjustments. Given its neutral effects on diastolic and atrial functions, RAE seems more suitable for reducing blood pressure in hypertensive patients with IHD.

Aim: The aim of our study was to compare ivabradine versus bisoprolol in the short-term and long-term treatment of inappropriate sinus tachycardia., Methods: From this prospective, parallel-group, open-label study, consecutive patients affected by inappropriate sinus tachycardia received ivabradine or bisoprolol and were evaluated with Holter ECG, ECG stress test, European Heart Rhythm Association score and Minnesota Living With Heart Failure Questionnaire at baseline, after 3 and 24 months., Results: Overall, 40 patients were enrolled. Baseline parameters were comparable in the ivabradine and bisoprolol subgroups. Two patients had transient phosphenes with ivabradine and two others interrupted the drug after 3 months as they planned to become pregnant. Eight individuals treated with bisoprolol experienced hypotension and weakness, which caused drug discontinuation in five of them. Ivabradine was superior to bisoprolol in reducing Holter ECG mean heart rate (HR) and mean HR during daytime at short- and long-term follow-up. Moreover, ivabradine but not bisoprolol significantly reduced Holter ECG mean HR during night-time as well as maximal and minimal HR and significantly increased the time duration and maximal load reached at ECG stress test. The quality of life questionnaires significantly improved in both subgroups., Conclusion: This study suggests that ivabradine is better tolerated than bisoprolol and seems to be superior in controlling the heart rate and improving exercise capacity in a small population of individuals affected by inappropriate sinus tachycardia during a short-term and long-term follow-up., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Patients with heart failure (HF) who contract SARS-CoV-2 infection are at a higher risk of cardiovascular and non-cardiovascular morbidity and mortality. Regardless of therapeutic attempts in COVID-19, vaccination remains the most promising global approach at present for controlling this disease. There are several concerns and misconceptions regarding the clinical indications, optimal mode of delivery, safety and efficacy of COVID-19 vaccines for patients with HF. This document provides guidance to all healthcare professionals regarding the implementation of a COVID-19 vaccination scheme in patients with HF. COVID-19 vaccination is indicated in all patients with HF, including those who are immunocompromised (e.g. after heart transplantation receiving immunosuppressive therapy) and with frailty syndrome. It is preferable to vaccinate against COVID-19 patients with HF in an optimal clinical state, which would include clinical stability, adequate hydration and nutrition, optimized treatment of HF and other comorbidities (including iron deficiency), but corrective measures should not be allowed to delay vaccination. Patients with HF who have been vaccinated against COVID-19 need to continue precautionary measures, including the use of facemasks, hand hygiene and social distancing. Knowledge on strategies preventing SARS-CoV-2 infection (including the COVID-19 vaccination) should be included in the comprehensive educational programmes delivered to patients with HF., (© 2021 European Society of Cardiology.)

Aims: To assess the clinical relevance of a history of atrial fibrillation (AF) in hospitalized patients with coronavirus disease 2019 (COVID-19)., Methods and Results: We enrolled 696 consecutive patients (mean age 67.4 ± 13.2 years, 69.7% males) admitted for COVID-19 in 13 Italian cardiology centres between 1 March and 9 April 2020. One hundred and six patients (15%) had a history of AF and the median hospitalization length was 14 days (interquartile range 9-24). Patients with a history of AF were older and with a higher burden of cardiovascular risk factors. Compared to patients without AF, they showed a higher rate of in-hospital death (38.7% vs. 20.8%; P < 0.001). History of AF was associated with an increased risk of death after adjustment for clinical confounders related to COVID-19 severity and cardiovascular comorbidities, including history of heart failure (HF) and increased plasma troponin [adjusted hazard ratio (HR): 1.73; 95% confidence interval (CI) 1.06-2.84; P = 0.029]. Patients with a history of AF also had more in-hospital clinical events including new-onset AF (36.8% vs. 7.9%; P < 0.001), acute HF (25.3% vs. 6.3%; P < 0.001), and multiorgan failure (13.9% vs. 5.8%; P = 0.010). The association between AF and worse outcome was not modified by previous or concomitant use of anticoagulants or steroid therapy (P for interaction >0.05 for both) and was not related to stroke or bleeding events., Conclusion: Among hospitalized patients with COVID-19, a history of AF contributes to worse clinical course with a higher mortality and in-hospital events including new-onset AF, acute HF, and multiorgan failure. The mortality risk remains significant after adjustment for variables associated with COVID-19 severity and comorbidities., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Aims: Myocardial injury (MI) in coronavirus disease-19 (COVID-19) is quite prevalent at admission and affects prognosis. Little is known about troponin trajectories and their prognostic role. We aimed to describe the early in-hospital evolution of MI and its prognostic impact., Methods and Results: We performed an analysis from an Italian multicentre study enrolling COVID-19 patients, hospitalized from 1 March to 9 April 2020. MI was defined as increased troponin level. The first troponin was tested within 24 h from admission, the second one between 24 and 48 h. Elevated troponin was defined as values above the 99th percentile of normal values. Patients were divided in four groups: normal, normal then elevated, elevated then normal, and elevated. The outcome was in-hospital death. The study population included 197 patients; 41% had normal troponin at both evaluations, 44% had elevated troponin at both assessments, 8% had normal then elevated troponin, and 7% had elevated then normal troponin. During hospitalization, 49 (25%) patients died. Patients with incident MI, with persistent MI, and with MI only at admission had a higher risk of death compared with those with normal troponin at both evaluations (P < 0.001). At multivariable analysis, patients with normal troponin at admission and MI injury on Day 2 had the highest mortality risk (hazard ratio 3.78, 95% confidence interval 1.10-13.09, P = 0.035)., Conclusions: In patients admitted for COVID-19, re-test MI on Day 2 provides a prognostic value. A non-negligible proportion of patients with incident MI on Day 2 is identified at high risk of death only by the second measurement., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Spectral analysis of heart rate variability (HRV) is a long-standing technique to indirectly assess neural cardiac regulation. This article specifically addressed how spectral analysis of HRV could help to understand neural cardiovascular adaptations to long-term exercise training; and inform us on training status in athletes. We reviewed literature searching for articles investigating resting cardiovascular adaptations to long-term exercise training through spectral analysis of HRV in athletes, from amateur to world class categories, practicing different sport disciplines, and focusing, in particular, on a series of work performed over time in our laboratory, which may highlight how different types of exercise training differently affect neural cardiac regulation. Spectral analysis of HRV has been shown its capability of detecting different adaptational changes in cardiac autonomic nervous system (ANS) regulation attending physical training in athletes of different sport disciplines. Studies showed that spectral analysis of HRV provide results that are sport-dependent and differ at individual level. ANS adaptations to exercise training are presented and discussed. Reported studies indicate that spectral analysis of HRV is an effective tool to monitor and optimize the training process and to predict athletic achievements in competitions. Cardiac ANS adaptations are strongly dependant on the type of training being performed. The individual nature of cardiac ANS adaptations should be considered to properly interpret the observed findings.

Heart failure (HF) characterized by cardiac remodeling is a condition in which inflammation and fibrosis play a key role. Dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) seems to produce good results. In fact, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory and antioxidant properties and different cardioprotective mechanisms. In particular, following their interaction with the nuclear factor erythropoietin 2 related factor 2 (NRF2), the free fatty acid receptor 4 (Ffar4) receptor, or the G-protein coupled receptor 120 (GPR120) fibroblast receptors, they inhibit cardiac fibrosis and protect the heart from HF onset. Furthermore, n-3 PUFAs increase the left ventricular ejection fraction (LVEF), reduce global longitudinal deformation, E/e ratio (early ventricular filling and early mitral annulus velocity), soluble interleukin-1 receptor-like 1 (sST2) and high-sensitive C Reactive protein (hsCRP) levels, and increase flow-mediated dilation. Moreover, lower levels of brain natriuretic peptide (BNP) and serum norepinephrine (sNE) are reported and have a positive effect on cardiac hemodynamics. In addition, they reduce cardiac remodeling and inflammation by protecting patients from HF onset after myocardial infarction (MI). The positive effects of PUFA supplementation are associated with treatment duration and a daily dosage of 1-2 g. Therefore, both the European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association (ACC/AHA) define dietary supplementation with n-3 PUFAs as an effective therapy for reducing the risk of hospitalization and death in HF patients. In this review, we seek to highlight the most recent studies related to the effect of PUFA supplementation in HF. For that purpose, a PubMed literature survey was conducted with a focus on various in vitro and in vivo studies and clinical trials from 2015 to 2021.

Background: Pulmonary embolism (PE) has been described in coronavirus disease 2019 (COVID-19) critically ill patients, but the evidence from more heterogeneous cohorts is limited., Methods: Data were retrospectively obtained from consecutive COVID-19 patients admitted to 13 Cardiology Units in Italy, from March 1st to April 9th, 2020, and followed until in-hospital death, discharge, or April 23rd, 2020. The association of baseline variables with computed tomography-confirmed PE was investigated by Cox hazards regression analysis. The relationship between D-dimer levels and PE incidence was evaluated using restricted cubic splines models., Results: The study included 689 patients (67.3 ± 13.2 year-old, 69.4% males), of whom 43.6% were non-invasively ventilated and 15.8% invasively. 52 (7.5%) had PE over 15 (9-24) days of follow-up. Compared with those without PE, these subjects had younger age, higher BMI, less often heart failure and chronic kidney disease, more severe cardio-pulmonary involvement, and higher admission D-dimer [4344 (1099-15,118) vs. 818.5 (417-1460) ng/mL, p < 0.001]. They also received more frequently darunavir/ritonavir, tocilizumab and ventilation support. Furthermore, they faced more bleeding episodes requiring transfusion (15.6% vs. 5.1%, p < 0.001) and non-significantly higher in-hospital mortality (34.6% vs. 22.9%, p = 0.06). In multivariate regression, only D-dimer was associated with PE (HR 1.72, 95% CI 1.13-2.62; p = 0.01). The relation between D-dimer concentrations and PE incidence was linear, without inflection point. Only two subjects had a baseline D-dimer < 500 ng/mL., Conclusions: PE occurs in a sizable proportion of hospitalized COVID-19 patients. The implications of bleeding events and the role of D-dimer in this population need to be clarified.

Background: Glucocorticoid therapy has emerged as an effective therapeutic option in hospitalized patients with coronavirus disease 2019 (COVID-19). This study aimed to focus on the impact of relevant clinical and laboratory factors on the protective effect of glucocorticoids on mortality., Methods: A sub-analysis was performed of the multicenter Cardio-COVID-Italy registry, enrolling consecutive patients with COVID-19 admitted to 13 Italian cardiology units between 01 March 2020 and 09 April 2020. The primary endpoint was in-hospital mortality., Results: A total of 706 COVID-19 patients were included (349 treated with glucocorticoids, 357 not treated with glucocorticoids). After adjustment for relevant covariates, use of glucocorticoids was associated with a lower risk of in-hospital mortality (adjusted HR 0.44; 95% CI 0.26-0.72; p = 0.001). A significant interaction was observed between the protective effect of glucocorticoids on mortality and PaO 2 /FiO 2 ratio on admission (p = 0.042), oxygen saturation on admission (p = 0.017), and peak CRP (0.023). Such protective effects of glucocorticoids were mainly observed in patients with lower PaO 2 /FiO 2 ratio (<300), lower oxygen saturation (<90%), and higher CRP (>100 mg/L)., Conclusions: The protective effects of glucocorticoids on mortality in COVID-19 were more evident among patients with worse respiratory parameters and higher systemic inflammation., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Despite guideline recommendations and available evidence, implementation of treatment in heart failure (HF) is poor. The majority of patients are not prescribed drugs at target doses that have been proven to positively impact morbidity and mortality. Among others, tolerability issues related to low blood pressure, heart rate, impaired renal function or hyperkalaemia are responsible. Chronic kidney disease plays an important role as it affects up to 50% of patients with HF. Also, dynamic changes in estimated glomerular filtration rate may occur during the course of HF, resulting in inappropriate dose reduction or even discontinuation of decongestive or neurohormonal modulating therapy in clinical practice. As patients with HF are rarely naïve to pharmacologic therapies, the challenge is to adequately prioritize or select the most appropriate up-titration schedule according to patient profile. In this consensus document, we identified nine patient profiles that may be relevant for treatment implementation in HF patients with a reduced ejection fraction. These profiles take into account heart rate (<60 bpm or >70 bpm), the presence of atrial fibrillation, symptomatic low blood pressure, estimated glomerular filtration rate (<30 or >30 mL/min/1.73 m 2 ) or hyperkalaemia. The pre-discharge patient, frequently still congestive, is also addressed. A personalized approach, adjusting guideline-directed medical therapy to patient profile, may allow to achieve a better and more comprehensive therapy for each individual patient than the more traditional, forced titration of each drug class before initiating treatment with the next., (© 2021 European Society of Cardiology.)

Short-term blood pressure (BP) variability (BPV), measured by 24-h ambulatory BP monitoring (ABPM), has been independently related to a higher risk of cardiovascular events and target organ in hypertensive patients. The aim of this study was to compare the effects of two different exercise modalities on BPV in hypertensive patients enrolled in a cardiac rehabilitation program. This study is a randomized trial, with two intervention arms: 1 ) aerobic training (AT) and 2 ) combined aerobic and resistance training (CT). We studied 55 male patients with hypertension. They were randomly assigned either to AT or CT group. The training program lasted 12 wk for each group. Short-term BP variability was evaluated by means of average real variability (ARV), at baseline and after 12 wk, by ABPM. Systolic and diastolic 24-h BP values decreased significantly ( P < 0.01) in both groups, without between-groups differences ( P = 0.11). The 24-h systolic BP variability decreased in both groups (AT: from 8.4 ± 1.2 to 7.6 ± 0.8; CT: from 8.8 ± 1.5 to 7.1 ± 1.1), with a greater decrease in CT ( P = 0.02). Night-time systolic BPV decreased in CT (from 9.4 ± 1.3 to 8.3 ± 1.2, P = 0.03) and remained unchanged in AT (from 9.5 ± 1.2 to 9.4 ± 1.4). Day-time BPV decreased in both groups without between-groups differences ( P = 0.07). CT was more effective than AT in reducing short-term BPV in hypertensive patients, and both exercise modalities reduced BP to a same extent. CT appears to be a more appropriate exercise modality if the objective is to reduce BPV in addition to BP levels. NEW & NOTEWORTHY Combined exercise training (CT) including aerobic plus resistance exercises could be more effective in comparison with aerobic exercise (AT) alone in reducing blood pressure variability (BPV) in hypertensive patients. We report that CT was indeed more effective than AT in reducing short-term BPV, and both exercise modalities reduced BP levels to the same extent. CT appears to be a more appropriate exercise modality if the objective is to reduce BPV in addition to BP levels.

Background: In this study, we aimed at comparing the effects of three different exercise modalities on post-exercise hypotension (PEH) in elderly hypertensive patients and at investigating whether PEH responses to the same exercises are affected by their training status., Methods: Thirty-six male sedentary hypertensive patients over 60 years old, were included. They were divided into three groups each one corresponding to a different exercise modality, i.e., aerobic continuous exercise (ACE), high-intensive interval exercise (HIIE), and combined (aerobic and resistance) exercise (CE). PEH was assessed in each group by ambulatory blood pressure monitoring (ABPM) in two different conditions as follows: (1) sedentary status and (2) trained status, at the end of a 12 week of ACE training program. A cardiopulmonary test was performed before and at the end of the training program., Results: In the sedentary status, 24-h and nocturnal systolic and diastolic blood pressure (BP) decreased in all groups as compared with top pre-exercise, with a greater but not significant reduction in the ACE and CE groups as compared with HIIE. ACE and HIIE groups presented a more sustained PEH than CE. In the trained status, 24-h and nighttime systolic and diastolic BP decreased significantly only after HIIE, but were unchanged as compared with pre-exercise in the ACE and CE groups., Conclusions: ACE and CE produced greater PEH than HIIE in sedentary elderly hypertensive patients. However, after training, HIIE produced the greater and more sustained PEH. The training status appears to exert significant effects on PEH produced by different exercise modalities.

There is evidence demonstrating that heart failure (HF) occurs in 1-2% of the global population and is often accompanied by comorbidities which contribute to increasing the prevalence of the disease, the rate of hospitalization and the mortality. Although recent advances in both pharmacological and non-pharmacological approaches have led to a significant improvement in clinical outcomes in patients affected by HF, residual unmet needs remain, mostly related to the occurrence of poorly defined strategies in the early stages of myocardial dysfunction. Nutritional support in patients developing HF and nutraceutical supplementation have recently been shown to possibly contribute to protection of the failing myocardium, although their place in the treatment of HF requires further assessment, in order to find better therapeutic solutions. In this context, the Optimal Nutraceutical Supplementation in Heart Failure (ONUS-HF) working group aimed to assess the optimal nutraceutical approach to HF in the early phases of the disease, in order to counteract selected pathways that are imbalanced in the failing myocardium. In particular, we reviewed several of the most relevant pathophysiological and molecular changes occurring during the early stages of myocardial dysfunction. These include mitochondrial and sarcoplasmic reticulum stress, insufficient nitric oxide (NO) release, impaired cardiac stem cell mobilization and an imbalanced regulation of metalloproteinases. Moreover, we reviewed the potential of the nutraceutical supplementation of several natural products, such as coenzyme Q10 (CoQ10), a grape seed extract, Olea Europea L.-related antioxidants, a sodium-glucose cotransporter (SGLT2) inhibitor-rich apple extract and a bergamot polyphenolic fraction, in addition to their support in cardiomyocyte protection, in HF. Such an approach should contribute to optimising the use of nutraceuticals in HF, and the effect needs to be confirmed by means of more targeted clinical trials exploring the efficacy and safety of these compounds.

The aims of this paper were to provide an overview of available activity monitors used in research in patients with heart failure and to identify the key criteria in the selection of the most appropriate activity monitor for collecting, reporting, and analysing physical activity in heart failure research. This study was conducted in three parts. First, the literature was systematically reviewed to identify physical activity concepts and activity monitors used in heart failure research. Second, an additional scoping literature search for validation of these activity monitors was conducted. Third, the most appropriate criteria in the selection of activity monitors were identified. Nine activity monitors were evaluated in terms of size, weight, placement, costs, data storage, water resistance, outcomes and validation, and cut-off points for physical activity intensity levels were discussed. The choice of a monitor should depend on the research aims, study population and design regarding physical activity. If the aim is to motivate patients to be active or set goals, a less rigorously tested tool can be considered. On the other hand, if the aim is to measure physical activity and its changes over time or following treatment adjustment, it is important to choose a valid activity monitor with a storage and battery longevity of at least one week. The device should provide raw data and valid cut-off points should be chosen for analysing physical activity intensity levels. Other considerations in choosing an activity monitor should include data storage location and ownership and the upfront costs of the device., (© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background and Purpose: When switching between monoamine oxidase type B (MAO-B) inhibitors, a 15-day suspension period is a precautionary measure to avoid a serotonin syndrome and hypertensive crisis. However, this indication results in a major inconvenience for parkinsonian patients because of the worsening of their clinical condition. In routine clinical practice, neurologists often perform a substitution of these two drugs without solution of continuity (i.e. overnight), to avoid worsening of fluctuations and prolonged OFF periods. Therefore, a safety open label study was performed to investigate the possible risks of switching overnight from rasagiline to safinamide., Methods: The study population included 20 advanced patients with Parkinson's disease on stable treatment with rasagiline and levodopa (alone or in combination with other anti-parkinsonian medication). The possible occurrence of serotonin syndrome and hypertension was monitored through a strict clinical observation and a 24-h Holter recording (ABPM) performed twice, whilst subjects were on rasagiline and immediately after switching to safinamide., Results: No cases of serotonin syndrome or hypertensive crisis occurred during the study. Changes that were not significant occurred in the primary end-point: 24-h mean blood pressure (BP) had a mild +4.4% increase in the ABPM2 versus ABPM1 (P = 0.17), 24-h systolic and diastolic BP values were slightly higher at ABPM2 compared to ABPM1 (respectively +3.3%, P = 0.13; and 5.4%, P = 0.08) and 24-h systolic BP variability was unchanged between the two ABPM evaluations (from 8.6 ± 2.9 to 8.9 ± 1.8; P = 0.27)., Conclusion: The results of the present study confirm that the overnight switch from rasagiline to safinamide is safe and well tolerated by patients., (© 2020 European Academy of Neurology.)

Aims: To assess the prognostic value of a history of heart failure (HF) in patients with coronavirus disease 2019 (COVID-19)., Methods and Results: We enrolled 692 consecutive patients admitted for COVID-19 in 13 Italian cardiology centres between 1 March and 9 April 2020. Mean age was 67.4 ± 13.2 years, 69.5% of patients were males, 90 (13.0%) had a history of HF, median hospitalization length was 14 days (interquartile range 9-24). In-hospital death occurred in 37 of 90 patients (41.1%) with HF history vs. 126 of those with no HF history (20.9%). The increased risk of death associated with HF history remained significant after adjustment for clinical variables related to COVID-19 and HF severity, including comorbidities, oxygen saturation, lymphocyte count and plasma troponin [adjusted hazard ratio (HR) for death: 2.25; 95% confidence interval (CI) 1.26-4.02; P = 0.006 at multivariable Cox regression model including 404 patients]. Patients with a history of HF also had more in-hospital complications including acute HF (33.3% vs. 5.1%, P < 0.001), acute renal failure (28.1% vs. 12.9%, P < 0.001), multiorgan failure (15.9% vs. 5.8%, P = 0.004) and sepsis (18.4% vs. 8.9%, P = 0.006). Other independent predictors of outcome were age, sex, oxygen saturation and oxygen partial pressure at arterial gas analysis/fraction of inspired oxygen ratio (PaO 2 /FiO 2 ). In-hospital treatment with corticosteroids and heparin had beneficial effects (adjusted HR for death: 0.46; 95% CI 0.29-0.74; P = 0.001; n = 404 for corticosteroids, and adjusted HR 0.41; 95% CI 0.25-0.67; P < 0.001; n = 364 for heparin)., Conclusions: Hospitalized patients with COVID-19 and a history of HF have an extremely poor outcome with higher mortality and in-hospital complications. HF history is an independent predictor of increased in-hospital mortality., (© 2020 European Society of Cardiology.)

Importance: Myocardial injury, detected by elevated plasma troponin levels, has been associated with mortality in patients hospitalized with coronavirus disease 2019 (COVID-19). However, the initial data were reported from single-center or 2-center studies in Chinese populations. Compared with these patients, European and US patients are older, with more comorbidities and higher mortality rates., Objective: To evaluate the prevalence and prognostic value of myocardial injury, detected by elevated plasma troponin levels, in a large population of White Italian patients with COVID-19., Design, Setting, and Participants: This is a multicenter, cross-sectional study enrolling consecutive patients with laboratory-confirmed COVID-19 who were hospitalized in 13 Italian cardiology units from March 1 to April 9, 2020. Patients admitted for acute coronary syndrome were excluded. Elevated troponin levels were defined as values greater than the 99th percentile of normal values., Main Outcomes and Measures: Clinical characteristics and outcomes stratified as elevated or normal cardiac troponin levels at admission, defined as troponin T or troponin I at a level greater than the 99th percentile of normal values., Results: A total of 614 patients with COVID-19 were included in this study (mean age [SD], 67 [13] years; 70.8% male), of whom 148 patients (24.1%) died during the hospitalization. Elevated troponin levels were found in 278 patients (45.3%). These patients were older (mean [SD] age, 64.0 [13.6] years vs 71.3 [12.0] years; P < .001) and had higher prevalence of hypertension (168 patients [50.5%] vs 182 patients [65.9%]; P < .001), heart failure (24 [7.2%]; 63 [22.8%]; P < .001), coronary artery disease (50 [15.0%] vs 87 [31.5%]; P < .001), and atrial fibrillation (33 [9.9%] vs 67 [24.3%]; P < .001). Elevated troponin levels were associated with an increased in-hospital mortality (37% vs 13%; HR, 1.71 [95% CI, 1.13-2.59]; P = .01 via multivariable Cox regression analysis), and this was independent from concomitant cardiac disease. Elevated troponin levels were also associated with a higher risk of in-hospital complications: heart failure (44 patients [19.2%] vs 7 patients [2.9%]; P < .001), sepsis (31 [11.7%] vs 21 [6.4%]; P = .03), acute kidney failure (41 [20.8%] vs 13 [6.2%]; P < .001), multiorgan failure (21 [10.9%] vs 6 [2.9%]; P = .003), pulmonary embolism (27 [9.9%] vs 17 [5.2%]; P = .04), delirium (13 [6.8%] vs 3 [1.5%]; P = .02), and major bleeding (16 [7.0%] vs 4 [1.6%]; P = .008)., Conclusions and Relevance: In this multicenter, cross-sectional study of Italian patients with COVID-19, elevated troponin was an independent variable associated with in-hospital mortality and a greater risk of cardiovascular and noncardiovascular complications during a hospitalization for COVID-19.

Aims: The aims of this study were to evaluate if the risk of cardiovascular events and all-cause mortality was higher in the presence of hyperkalaemia (HK) in patients with heart failure (HF) treated with renin-angiotensin-aldosterone system inhibitors (RAASi), and to investigate in this cohort the increased risk of cardiovascular events and all-cause mortality among HK patients with non-optimal adherence to RAASi therapy., Methods and Results: In this retrospective cohort study based on administrative databases of five Italian Local Health Units, all adult patients with a HF diagnosis between January 2010 and December 2017 were included only if they were prescribed RAASi therapy during the first 3 months after the index date, that corresponded to the date of first HF diagnosis during the inclusion period. Patients were considered to have HK if serum potassium level was ≥5.5 mmol/L. A propensity score matching was applied before evaluation of hazard ratios. Patients with HK were 37% (P < 0.001) and 70% (P < 0.001), respectively, more at risk of cardiovascular events and of dying for all-cause mortality compared to non-HK patients. Among the HK group, patients non-adherent to RAASi therapy had a 39% (P = 0.105) higher risk of cardiovascular events and a twofold increased risk (P < 0.001) of all-cause death., Conclusion: Findings from this real-world study showed that in a cohort of HF patients under RAASi therapy, subjects with HK had an enhanced risk of cardiovascular events or death compared to patients without HK. Moreover, in HK patients, sub-optimal adherence to RAASi therapy was associated with an increased risk of all-cause mortality., (© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

In the south-central Italy, during summer rainfall does not supply a sufficient amount of water. Therefore, irrigation management during dry periods is important for maintaining turf quality. The hybrid bermudagrass (Cynodon dactylon (L.) Pers. × Cynodon transvaalensis Burtt-Davy) is known to represent the dominant warm-season turfgrass in warm to temperate climatic regions and its drought tolerance make bermudagrass a competitive turfgrass. A greenhouse experiment was conducted using uniform cores of hybrid bermudagrass, which were secured in a polyvinyl chloride cylinders and watered by constant sub-irrigation. The objectives of the present research were to measure the spectral reflectance with a new generation handheld spectroradiometer on hybrid bermudagrass and to explore various vegetation indices to be used as future detecting tool to study water stress in bermudagrass. Moreover, the potential uses of multivariate processing techniques for discriminating different water stress conditions in turfgrass has been investigated. Besides spectral indices, multivariate methods, although performed on a data set limited in terms of sample size, have shown a great potential for water stress monitoring in turfgrass and surely deserve further investigations. There are different indices that use distinct water absorption features independent of chlorophyll concentration, such as water index (WI = R900/R970) that has been reported to be a robust index of canopy water content and is used as an active indicator of changes in Leaf Relative Water Content (LRWC). Also, the ratio of WI with NDVI (WI/NDVI = (R 900 /R 970 )/((R 800  - R 680 )/(R 800  + R 680 )]) was found to be an effective indicator of water stress. Another vegetation index to detect water features is normalized difference water index (NDWI), designed to maximize reflectance of water by using green wavelengths. In our trial in bermudagrass the relationships studied, suggest that WI (900/970) and WI/NDVI, among the indices studied, are the more effective indicators of water stress. In fact, lower values of WI indicate higher water stress, while higher values of WI/NDVI indicate higher water stress levels.

Venous thromboembolism (VTE), including pulmonary embolism and deep venous thrombosis, either symptomatic or incidental, is a common complication in the history of cancer disease. The risk of VTE is 4-7-fold higher in oncology patients, and it represents the second leading cause of death, after cancer itself. In cancer patients, compared with the general population, VTE therapy is associated with higher rates of recurrent thrombosis and/or major bleeding. The need for treatment of VTE in patients with cancer is a challenge for the clinician because of the multiplicity of types of cancer, the disease stage and the imbricated cancer treatment. Historically, in cancer patients, low molecular weight heparins have been preferred for treatment of VTE. More recently, in large randomized clinical trials, direct oral anticoagulants (DOACs) demonstrated to reduce the risk of VTE. However, in the "real life", uncertainties remain on the use of DOACs, especially for the bleeding risk in patients with gastrointestinal cancers and the potential drug-to-drug interactions with specific anticancer therapies.In cancer patients, atrial fibrillation can arise as a perioperative complication or for the side effect of some chemotherapy agents, as well as a consequence of some associated risk factors, including cancer itself. The current clinical scores for predicting thrombotic events (CHA2DS2-VASc) or for predicting bleeding (HAS-BLED), used to guide antithrombotic therapy in the general population, have not yet been validated in cancer patients. Encouraging data for DOAC prescription in patients with atrial fibrillation and cancer are emerging: recent post-hoc analysis showed safety and efficacy of DOACs for the prevention of embolic events compared to warfarin in cancer patients. Currently, anticoagulant therapy of cancer patients should be individualized with multidisciplinary follow-up and frequent reassessment. This consensus document represents an advanced state of the art on the subject and provides useful notes on clinical practice.

Turfgrasses are monocotyledonous plants from the family Poaceae. They are widely used in green spaces and are considered one of the most economically important horticultural crops in the world. Turfgrass quality is affected by several environmental factors including light, which is involved in the quality decline of transplanted sod. Ultraviolet-B (UV-B) is an important regulator of plant growth and development. Plants growing and/or stored in protected systems, such as in sod production, may be more vulnerable to UV-B damage than those growing in the field due to acclimation. Few studies on the effects of UV-B on turfgrass physiology have been published. Therefore, the aim of this study was to evaluate the influence of UV-B irradiation on the photosynthetic performance of five cool-season turfgrasses, namely Agrostis stolonifera L., Festuca arundinacea Schreb., Poa supina Schrad., Poa pratensis L. and Lolium perenne L. Turfgrasses were exposed to 18.25 kJ m -2 d -1 biologically effective UV-B in growth chambers under controlled conditions. Measurements included photosynthetic pigments, chlorophyll fluorescence and gas exchanges monitored for 16 d-UV-B treatment and after recovery. Content of pigments decreased with UV-B exposure with significant differences among the species. UV-B also affected the photosystem II (PSII) efficiency depending on the exposure period and species. Similarly, gas exchange parameters showed different effects among species after UV-B exposure compromising the assimilation of CO 2 . Multivariate analysis highlighted three main clusters of species confirming their different UV-B tolerance and ability to restore PSII photochemistry after recovery, from which Festuca arundinacea resulted to be the most tolerant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Advances in technology now make it possible to manage heart failure (HF) from a remote to a telemonitoring approach using either noninvasive solutions or implantable devices. Nowadays, it is possible to monitor at-home parameters that can be recorded, stored and remotely transmitted to physicians, allowing them to make decisions for therapeutic modification, hospitalization or access to the emergency room. Standalone systems are available that are equipped with self-intelligence and are able to acquire and elaborate data that can inform the remote physician of impending decompensation before it results in additional complications. The development of miniature implantable devices, which could measure haemodynamic variables and transmit them to a monitor outside the body, offers the possibility for the physician to obtain more frequent evaluations of HF patients and the opportunity to take these data into account in management decisions. At present, several telemonitoring devices are available, but the only Food and Drug Administration-approved system is the cardio-microelectromechanical system, which is an implantable pulmonary arterial pressure (PAP) monitoring device that allows a direct monitoring of the PAP via a sensor implanted in the pulmonary artery. This information is then uploaded to a web-based interface from which healthcare providers can track the results and manage patients. At present, the challenge point for telemedicine management of HF is to find the more relevant biological parameter to monitor the clinical status., Competing Interests: Disclosure: The authors have no conflicts of interest to declare., (Copyright © 2020, Radcliffe Cardiology.)

Background and Aim: Non-Alcoholic Fatty Liver Disease (NAFLD) represents a risk factor for cardiovascular diseases. NAFLD is worsened by the simultaneous occurrence of type 2 diabetes mellitus (T2DM) causing an enhancement of inflammatory and fibrotic processes. Although insulin resistance appears the link between NAFLD and T2DM, current pharmacological treatments of T2DM failed to produce relevant benefits in preventing T2DM-related liver dysfunction. In this randomized, double blind, placebo-controlled clinical study, we evaluated the effect of Bergacyn, an innovative formulation originating from the combination of Bergamot Polyphenolic Fraction (BPF) and Cynara cardunculus (CyC)., Experimental Procedure: 80 adult patients with a history of at least 12 months of T2DM and NAFLD received orally BPF (300 mg/daily) Cyc (300 mg/daily), separately or formulated in combination 50/50% (Bergacyn; 300 mg/daily), or placebo all containing 300 mg of bergamot albedo fibers micronized and co-grinded as excipients., Results and Conclusion: Serum measurements and liver ultrasound analyses showed that concomitant administration of BPF and CyC produced significant improvement of NAFLD biomarkers in patients with T2DM. This effect was associated with a substantial reduction of oxidative stress/inflammatory biomarkers, thus contributing to a significant improvement of NO-mediated reactive vasodilation. Furthermore, the effect of Bergacyn showed a synergistic effect of both extracts, thus suggesting that this peculiar formulation represents a novel therapeutic strategy to counteract vascular inflammation and endothelial dysfunction in patients suffering from T2DM and NAFLD. Further studies in larger cohort of diabetic patients are required to better identify the potential of Bergacyn on metabolic disorders accompanying T2DM and NAFLD., Competing Interests: The authors declare no conflict of interest., (© 2020 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Type 2 diabetes mellitus (T2DM) is common in patients with heart failure (HF) and associated with considerable morbidity and mortality. Significant advances have recently occurred in the treatment of T2DM, with evidence of several new glucose-lowering medications showing either neutral or beneficial cardiovascular effects. However, some of these agents have safety characteristics with strong practical implications in HF [i.e. dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RA), and sodium-glucose co-transporter type 2 (SGLT-2) inhibitors]. Regarding safety of DPP-4 inhibitors, saxagliptin is not recommended in HF because of a greater risk of HF hospitalisation. There is no compelling evidence of excess HF risk with the other DPP-4 inhibitors. GLP-1 RAs have an overall neutral effect on HF outcomes. However, a signal of harm suggested in two small trials of liraglutide in patients with reduced ejection fraction indicates that their role remains to be defined in established HF. SGLT-2 inhibitors (empagliflozin, canagliflozin and dapagliflozin) have shown a consistent reduction in the risk of HF hospitalisation regardless of baseline cardiovascular risk or history of HF. Accordingly, SGLT-2 inhibitors could be recommended to prevent HF hospitalisation in patients with T2DM and established cardiovascular disease or with multiple risk factors. The recently completed trial with dapagliflozin has shown a significant reduction in cardiovascular mortality and HF events in patients with HF and reduced ejection fraction, with or without T2DM. Several ongoing trials will assess whether the results observed with dapagliflozin could be extended to other SGLT-2 inhibitors in the treatment of HF, with either preserved or reduced ejection fraction, regardless of the presence of T2DM. This position paper aims to summarise relevant clinical trial evidence concerning the role and safety of new glucose-lowering therapies in patients with HF., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Several devices have been developed for heart failure (HF) treatment and monitoring. Among device-based monitoring tools, CardioMEMS™ has received growing research attention. This document reflects the key points of an ESC consensus meeting on implantable devices for monitoring in HF, with a particular focus on CardioMEMS™., (Published on behalf of the European Society of Cardiology. © The Author(s) 2019.)

Telemedicine and remote monitoring represent more than the communication of health data via a 'remote connection'. Modern systems can be stand-alone and can be equipped with the ability to acquire and summarize data in order to inform the patient, carer or health care giver. The information can be held locally or be shared with a health care centre. Contemporary telemedicine and telemonitoring solutions have shifted their focus, trying to work on a system which is ubiquitous, efficient and sustainable. Along with devices that collect and elaborate data, a new generation of plug and play sensors has also come to life, which with standardization can lower management costs and make introduction into practice more feasible. Multiple trials (TIM-HF, TEN-HMS and BEAT.HF) have reported varying outcomes, depending on the monitoring system and the background health care process. A special mention is necessary for home tele-rehabilitation programmes for patients with heart failure. Despite the progress obstacles remain, including adequate training, data ownership and handling and applicability to larger populations. This article will review contemporary advances in this area., (Published on behalf of the European Society of Cardiology. © The Author(s) 2019.)

The European Society of Cardiology (ESC) has published a series of guidelines on heart failure (HF) over the last 25 years, most recently in 2016. Given the amount of new information that has become available since then, the Heart Failure Association (HFA) of the ESC recognized the need to review and summarise recent developments in a consensus document. Here we report from the HFA workshop that was held in January 2019 in Frankfurt, Germany. This expert consensus report is neither a guideline update nor a position statement, but rather a summary and consensus view in the form of consensus recommendations. The report describes how these guidance statements are supported by evidence, it makes some practical comments, and it highlights new research areas and how progress might change the clinical management of HF. We have avoided re-interpretation of information already considered in the 2016 ESC/HFA guidelines. Specific new recommendations have been made based on the evidence from major trials published since 2016, including sodium-glucose co-transporter 2 inhibitors in type 2 diabetes mellitus, MitraClip for functional mitral regurgitation, atrial fibrillation ablation in HF, tafamidis in cardiac transthyretin amyloidosis, rivaroxaban in HF, implantable cardioverter-defibrillators in non-ischaemic HF, and telemedicine for HF. In addition, new trial evidence from smaller trials and updated meta-analyses have given us the chance to provide refined recommendations in selected other areas. Further, new trial evidence is due in many of these areas and others over the next 2 years, in time for the planned 2021 ESC guidelines on the diagnosis and treatment of acute and chronic heart failure., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

In athletes, spectral analysis of HR variability (HRV) has been shown capable to detect the adaptational changes in sympatho-vagal control attending physical training. So far, studies investigated autonomic nervous system (ANS) changes occurring with endurance training, whereas adaptations to markedly different exercise modes, for example, strength training, have never been investigated. We assessed the changes in cardiac ANS parameters during long-term training in weight lifters of the Italian team preparing for the European Championship, where athletes competed for obtaining the pass for Olympic Games. We investigated nine athletes. Subject trained 3 sessions/day, 6 days a week. The intensity of strength exercises varied from 70% to 95% 1 RM. Training load (TL) was calculated as: volume (min) × intensity (%1RM).All ANS parameters were significantly and highly correlated on an individual basis to the dose of exercise with a second-order regression model (r 2 ranged from 0.96 to 0.99; P < 0.001). The low-frequency (LF) component of HRV and LF/HF ratio showed an initial increase with the progression of TL and then a decrease, resembling a bell-shaped curve with a minimum at the highest TL. The high-frequency (HF) component of HRV and R-R interval showed a reciprocal pattern, with an initial decrease with progression of TL followed by an increase, resembling an U-shaped curve with a maximum at the highest TL. These adaptations were at the opposite to those previously reported in endurance athletes. These results suggest that in Olympic weight lifters, ANS adaptations to training are dose-related on individual basis and that ANS adaptations are mainly sport-specific., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Background: Exercise training programmes (ETPs) are a crucial component in cardiac rehabilitation in heart failure (HF) patients. The Exercise Training in HF (ExTraHF) survey has reported poor implementation of ETPs in countries affiliated to the European Society of Cardiology (ESC). The aim of the present sub-analysis was to investigate the regional variations in the implementation of ETPs for HF patients., Methods and Results: The study was designed as a web-based survey of cardiac units, divided into five areas, according to the geographical location of the countries surveyed. Overall, 172 centres replied to the survey, in charge of 78 514 patients, differentiated in 52 Northern (n = 15 040), 48 Southern (n = 27 127), 34 Western (n = 11 769), 24 Eastern European (n = 12 748), and 14 extra-European centres (n = 11 830). Greater ETP implementation was observed in Western (76%) and Northern (63%) regions, whereas lower rates were seen in Southern (58%), Eastern European (50%) and extra-European (36%) regions. The leading barrier was the lack of resources in all (83-65%) but Western region (37%) where patients were enrolled in dedicated settings and specialized units (75%). In 40% of centres, non-inclusion of ETP in the national or local guideline pathway accounted for the lack of ETP implementation., Conclusion: Exercise training programmes are poorly implemented in the ESC affiliated countries, mainly because of the lack of resources and/or national and local guidelines. The linkage with dedicated cardiac rehabilitation centres (as in the Western region) or the model of local rehabilitation services adopted in Northern countries may be considered as options to overcome these gaps., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Background: The aim of this study was to compare the acute effects produced by a single bout of three different exercise modalities on short-term blood pressure variability., Methods: The study enrolled 21 sedentary male patients with hypertension and a mean age of 63 ± 7.2 years. Blood pressure variability was evaluated through ambulatory blood pressure monitoring that was performed twice: during an ordinary daily activity and after an exercise session lasting 60 minutes. Patients were divided into three groups according to the different exercise modality performed during the session: aerobic continuous training, interval training or combined training including aerobic and resistance training., Results: Twenty-four-hour systolic blood pressure variability increased in the interval training group, was unchanged in the aerobic continuous training group and decreased in the combined training group (intergroup P  = 0.03). Daytime systolic blood pressure variability increased in the interval training and aerobic continuous training groups while it decreased in the combined training group (intergroup P  = 0.0006). Twenty-four-hour diastolic blood pressure variability decreased in the aerobic continuous training and combined training groups while it increased in the interval training group (intergroup P  = 0.002)., Conclusion: Different training modalities have similar hypotensive action but exert different acute effects on blood pressure variability. Combined training seems to be the most suitable training modality for sedentary men with hypertension.

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF). Current knowledge on incidence, pathophysiology and natural history of HF in cardiomyopathies is limited, and distinct features of their therapeutic responses have not been systematically addressed. Therefore, this position paper focuses on epidemiology, pathophysiology, natural history and latest developments in treatment of HF in patients with dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies. In DCM, HF with reduced ejection fraction (HFrEF) has high incidence and prevalence and represents the most frequent cause of death, despite improvements in treatment. In addition, advanced HF in DCM is one of the leading indications for heart transplantation. In HCM, HF with preserved ejection (HFpEF) affects most patients with obstructive, and ∼10% of patients with non-obstructive HCM. A timely treatment is important, since development of advanced HF, although rare in HCM, portends a poor prognosis. In RCM, HFpEF is common, while HFrEF occurs later and more frequently in amyloidosis or iron overload/haemochromatosis. Irrespective of RCM aetiology, HF is a harbinger of a poor outcome. Recent advances in our understanding of the mechanisms underlying the development of HF in cardiomyopathies have significant implications for therapeutic decision-making. In addition, new aetiology-specific treatment options (e.g. enzyme replacement therapy, transthyretin stabilizers, immunoadsorption, immunotherapy, etc.) have shown a potential to improve outcomes. Still, causative therapies of many cardiomyopathies are lacking, highlighting the need for the development of effective strategies to prevent and treat HF in cardiomyopathies., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

High-dose statin (HDS) therapy is recommended to reduce low-density lipoprotein cholesterol (LDL-C); however, some patients are unable to tolerate the associated side effects. Nutraceuticals have shown efficacy in lowering LDL-C. The aim of this study was to evaluate whether the combination of low-dose statin (LDS) plus ezetimibe (EZE) or LDS plus nutraceutical (Armolipid Plus [ALP] containing red yeast rice, policosanol, and berberine) can lead to a higher proportion of high-risk patients achieving target LDL-C. A secondary objective was to assess the efficacy of triple combination LDS + EZE + ALP in resistant patients (LDL-C >70 mg/dl). A randomized, prospective, parallel-group, single-blind study was conducted in patients with coronary artery disease (n = 100) who had undergone percutaneous coronary intervention in the preceding 12 months, were HDS-intolerant, and were not at LDL-C target (<70 mg/dl) with LDS alone. Patients received either LDS + EZE or LDS + ALP. Of the 100 patients, 33 patients (66%) treated with LDS + EZE and 31 patients (62%) treated with LDS + ALP achieved target LDL-C after 3 months, which was maintained at 6 months. Patients who did not achieve the therapeutic goal received a triple combination of LDS + EZE + ALP for a further 3 months. At 6 months, 28 of 36 patients (78%) achieved LDL-C target. Overall, 92% of patients enrolled in this study were at target LDL-C at 6 months. No patients in any group experienced major side effects. In conclusion, in HDS-intolerant coronary artery disease patients, the combination of LDS plus EZE and/or ALP represents a valuable therapeutic option allowing most patients to reach target LDL-C within 3 to 6 months., (Copyright © 2018. Published by Elsevier Inc.)

Exercise training (ET) and secondary prevention measures in cardiovascular disease aim to stimulate early physical activity and to facilitate recovery and improve health behaviours. ET has also been proposed for heart failure patients with a ventricular assist device (VAD), to help recovery in the patient's functional capacity. However, the existing evidence in support of ET in these patients remains limited. After a review of current knowledge on the causes of the persistence of limitation in exercise capacity in VAD recipients, and concerning the benefit of ET in VAD patients, the Heart Failure Association of the European Society of Cardiology has developed the present document to provide practical advice on implementing ET. This includes appropriate screening to avoid complications and then starting with early mobilisation, ET prescription is individualised to meet the patient's needs. Finally, gaps in our knowledge are discussed., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Exercise training is increasingly promoted for physical and mental health and represents a major factor in both primary and secondary prevention of cardiovascular (CV) diseases. The beneficial effects of exercise, in part, can be ascribed to adaptations of neural CV regulation through several mechanisms. In this article, we summarize how exercise training affects neural CV regulation and outline the plasticity of neural network in the continuum from cardiac patients to elite athletes.

In the past few years, new oral anticoagulants (NOACs) targeting directly a single activated clotting factor, have been developed for the treatment of non-valvular atrial fibrillation (AF), which are currently recommended as first-line therapy in AF. The aim of this study is to provide an overall picture on the extent to which oral anticoagulation (OAC) with NOACs correspond to actually prescribed OAC therapy in an unselected, real world, population of consecutive patients with AF in Italy. Compliance with the therapy and quality of life were also assessed. A 50 cardiology unit network located in different geographic areas of Italy enrolled a total of 1742 consecutive outpatients with AF (54.6% males, 45.4% females, mean age 72.5 years). NOACs were prescribed in 56.1% patients and VKA in 43.9% (P < 0.0001). NOACs were significantly more prescribed than VKA in patients with high thrombo-embolic risk score (i.e., CHA 2 DS 2 -VASc > 2) (78.2 vs 67.3%, P < 0.0001), but also patients at low risk (i.e., CHA 2 DS 2 -VASc < 1 and HAS-BLED < 3) were still under OAC therapy with either NOACs (27%) or VKA (73%). Adherence to therapy (Morisky test) was greater in patients taking NOACs as was the quality of life. The ISPAF-2 study shows that in an Italian population of real-world patients with AF the prescription of OAC according to current guidelines and stroke-risk scoring system is rather high although it still needs to be improved. Contrary to recommendations, in a high proportion of low-risk patients, anticoagulation therapy, with either NOACs and VKA is still prescribed, and this exposes patients to unjustified risks.

Recent evidence supports the concept that progression of chronic heart failure (CHF) depends upon an imbalance of catabolic forces over the anabolic drive. In this regard, multiple hormonal deficiency syndrome (MHDS) significantly has impacts upon CHF progression, and is associated with a worse clinical status and increased mortality. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Therapy in Heart Failure) Registry (clinicaltrial.gov = NCT02335801) tests the hypothesis that anabolic deficiencies reduce survival in a large population of mild-to-moderate CHF patients. The T.O.S.CA. Registry is a prospective multicenter observational study coordinated by "Federico II" University of Naples, and involves 19 centers situated throughout Italy. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydroepiandrosterone , and insulin are measured at baseline and every year for a patient-average follow-up of 3 years. Subjects with CHF are divided into two groups: patients with one or no anabolic deficiency, and patients with two or more anabolic deficiencies at baseline. The primary endpoint is the composite of all-cause mortality and cardiovascular hospitalization. Secondary endpoints include the composite of all-cause mortality and hospitalization, the composite of cardiovascular mortality and cardiovascular hospitalization, and change of VO 2 peak. Patient enrollment started in April 2013, and was completed in July 2017. Demographics and main clinical characteristics of enrolled patients are provided in this article. Detailed cross-sectional results will be available in late 2018. The T.O.S.CA. Registry represents the most robust prospective observational trial on MHDS in the field of CHF. The study findings will advance our knowledge with regard to the intimate mechanisms of CHF progression and hopefully pave the way for future randomized clinical trials of single or multiple hormonal replacement therapies in CHF.