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The interest in n-3 polyunsaturated fatty acids (n-3 PUFAs), their favorable effects on the cardiovascular (CV) risk profile and prevention of CV events has been growing over the years, leading to their recommendation for secondary prevention in post myocardial infarction and hypertriglyceridemia. However, years later conflicting results provided by clinical trials have generated some doubts about their CV benefits, leading to a limited indication for the treatment of hypertriglyceridemia. Only recently, after the REDUCE-IT Trial results on CV events and mortality, n-3 PUFAs have recovered an indication in the international guidelines for hypertriglyceridemia in patients with Atherosclerotic Cardiovascular Disease (ASCVD) or with type 2 diabetes mellitus (T2DM) and other CV risk factors, already on statin therapy. Multiple beneficial CV effects have been highlighted, in addition to the well-known lipid-lowering function, such as anti-inflammatory, anti-thrombotic and endothelial function protective properties. Three formulations of n-3 PUFAs are currently available on the market, sharing some pharmacokinetic and pharmacodynamic characteristics, but also exhibiting peculiar mechanisms. Three major clinical trials evaluated the efficacy and safety of different formulations of n-3 PUFA: JELIS, REDUCE-IT and STRENGTH, with controversial results attributable to various factors. For the future, it could be useful to perform comparative studies between different formulations and placebo, in order to clarify these doubts.

Background to date, more than 243 million COVID-19 cases have been diagnosed globally, with 4.94 million deaths, 489.000 new cases and 8.474 deaths per day. In Italy there are currently 4.73 million cases and 132.000 deaths. It is well known that the entry of the SARS- CoV-2 virus into cells is mediated by the binding between the virus Spike-glycoprotein (S) and the membrane ACE2-receptor (ACE2-R). When SARS-CoV-2 binds to ACE2-R, with subsequent membrane fusion and virus entry into the cell, a down-regulation of these receptors occurs. ACE2 –R downregulation plays a crucial role in the pulmonary and systemic inflammatory response. A serious clinical course appears to be associated with some factors such as age, previous pathologies and comorbidities. However, also a dysregulation of the RAA system linked to a different expression of ACE-2 R and TMPRSS2 gene polymorphisms and different serum levels of soluble ACE2 (sACE2), could be associated with abnormal inflammatory and immune response to SARS-CoV-2 infection. Aim of the Study we aimed to verify whether there is an association between the clinical course of COVID-19 patients (pts) and the presence of more frequent ACE2 and TMPRSS2 single-nucleotide polymorphisms (SNPs) and if sACE2 levels are related to specific ACE2 and TMPRSS2 polymorphic variants. Methods we consecutively enrolled subjects with previous documented SARS-CoV-2 infection and divided our sample into three groups: pts with asymptomatic course; pts with symptomatic course but without the need for hospitalization for COVID-19; pts with severe symptomatic course requiring hospitalization in intensive care unit. Data about age, clinical course, comorbidities, and therapies were collected. Blood samples were taken for the genetic analysis of the most frequent SNPs of the ACE2-R and TMPRSS2 detected in Italian population, in particular genotypic variants TT and CC of ACE2 SNPs 1 and 5 (rate of 5% and 14% respectively) and genotypic variants TT and CC of TMPRSS2 SNPs 2 and 3 (rate of 50% and 30% respective). Results among 178 pts enrolled up to March 2022, we have so far analyzed the genetic polymorphisms of 74 pts.; 21 (28%) were hospitalized for COVID-19, 38 (51%) had symptomatic course without hospitalization and 15 (21%) were completely pauci-asymptomatics. Serum concentrations of sACE2 and distribution of polymorphic variants in the three groups are summarized in Table 1. We found that sACE2 levels were higher in genotypic variant CC of SNP 1 of TMPRSS2 gene (Table 2). Considering that a high concentration of sACE2 outlines a proinflammatory condition, it could be hypothesized that the CC genotype may be a predisposing condition to the cytokine storm of COVID-19. Perspectives: Genetic analysis of ACE2 and TMPRSS2 SNPs will help to clarify the relationship between these polymorphic variant, sACE2 levels, risk of SARS-CoV2 infection and severity of clinical presentation of COVID-19 in patients with or without CV diseases.

Background It is well known that the entry of the SARS- CoV-2 virus into cells is mediated by the binding between the virus Spike-glycoprotein (S) and the membrane ACE2-receptor (ACE2R). When SARS-CoV-2 binds to ACE2R, with subsequent membrane fusion and virus entry into the cell, a down-regulation of these receptors occurs. ACE2R downregulation plays a crucial role in the pulmonary and systemic inflammatory response. Also ACE2 deficiency is thought to play an important role in the pathogenesis of SARS-CoV-2 infection. The down-regulation of ACE2 induced by viral infection could be particularly harmful in subjects with pre-existing ACE2 deficiency, for example due to advanced age, the presence of DM, arterial hypertension or pre-existing heart disease, including HF. Literature data suggest an association between the patient's age and comorbidities and a greater risk of severe clinical course and with a worse prognosis. However, serious clinical pictures requiring hospitalization or leading to death have also been observed in young subjects or subjects without comorbidities. Aim of the Study we aimed to identify predicting factors of a higher risk in terms of severity of the clinical course and worse prognosis in the population of the Brescia area, affected by a large number of cases in the first period of COVID-19 outbreak. In particular, we aimed to verify whether there is correlation between levels of serum ACE2 (sACE2) and the risk of SARS-CoV-2 infection, as well as between sACE2 and the different severity of the clinical manifestations of COVID-19 in patients with and without CV diseases. Methods we consecutively enrolled subjects with previous documented SARS-CoV-2 infection and divided our sample into three groups: pts with asymptomatic course; pts with symptomatic course but without the need for hospitalization for COVID-19; pts with severe symptomatic course requiring hospitalization in intensive care unit. Blood samples were taken for sACE2 dosage. We compared the concentrations of sACE2 in these groups in relation to the age, clinical course, comorbidities, and ongoing therapies. Results at March 2022, we enrolled 178 pts, 51 (28%) were hospitalized for COVID-19, whereas 78 (44%) had symptomatic course without hospitalization and 49 (28%) were completely pauci-asymptomatic. Only 6 pts (4%) had myocarditis or pericarditis SARS-CoV-2-related. Between hospitalized pts, male sex (67%), older age and higher BMI were most frequent. Moreover, chronic heart failure (20%), a diagnosis of cardiopathy (29%) and AF or atrial flutter (22%) were most frequent (Table 1). Plasma concentrations of sACE2 will be dosed and analyzed in relation to the clinical characteristics of each patient. Perspectives ACCEPT study will help to clarify the relationship between ACE2 molecule, the risk of SARS-CoV2 infection and the severity of clinical presentation of COVID-19 in pts with or without CV diseases.

Despite recent advances in chronic heart failure (HF) therapy, the prognosis of HF patients remains poor, with high rates of HF rehospitalizations and death in the early months after discharge. This emphasizes the need for incorporating novel HF drugs, beyond the current approach (that of modulating the neurohumoral response). Recently, new antidiabetic oral medications (sodium-glucose cotransporter 2 inhibitors (SGLT2i)) have been shown to improve prognosis in diabetic patients with previous cardiovascular (CV) events or high CV risk profile. Data from DAPA-HF study showed that dapaglifozin is associated with a significant reduction in mortality and HF hospitalization as compared with placebo regardless of diabetes status. Recently, results from EMPEROR-Reduced HF trial were consistent with DAPA-HF trial findings, showing significant beneficial effect associated with empagliflozin use in a high-risk HF population with markedly reduced ejection fraction. Results from the HF with preserved ejection fraction trials using these same agents are eagerly awaited. This review summarizes the evidence for the use of gliflozins in HF treatment.

AIM To review published literature on the use of quick response (QR) codes within medical and cardiology settings. METHODS Medline, Scopus Search and Cochrane Library were used to conduct the research. Title and abstract review of 376 publications was performed. Papers which discussed the application of QR codes in medical setting were included. A total of 151 articles were reviewed and thematic analysis conducted to understand how QR codes are currently used in the medical setting, the medical areas in which they are mostly used, their applications in cardiovascular area. RESULTS The analysis of 151 articles revealed that QR code technology is mainly used in the medical field to: 1) collect data via survey, 2) educate medical staff or students and 3) provide information about therapies or surgery. The medical area in which QR codes are most used is the clinical one, but only 3.3% of publications concern cardiovascular settings. A third of the QR code-related articles of 2020 is about Covid-19. CONCLUSIONS Different uses of QR codes in medical setting are increasing. QR codes might represent an easy and convenient digital tool to collect data and implement telemedicine programs on a large scale involving also the cardiovascular setting., Graphical Abstract Graphical Abstract

CoronaVIrus Disease-19 (COVID-19) had a huge impact on human health and economy. However, to this date, the effects of the pandemic on the training of young cardiologists are only partially known. To assess the consequences of the pandemic on the education of the cardiologists in training, we performed a 23-item national survey that has been delivered to 1443 Italian cardiologists in training, registered in the database of the Italian Society of Cardiology (SIC). Six hundred and thirty-three cardiologists in training participated in the survey. Ninety-five percent of the respondents affirmed that the training programme has been somewhat stopped or greatly jeopardized by the pandemic. For 61% of the fellows in training (FITs), the pandemic had a negative effect on their education. Moreover, 59% of the respondents believe that they would not be able to fill the gap gained during that period over the rest of their training. A negative impact on the psycho-physical well being has been reported by 86% of the FITs. The COVID-19 pandemic had an unparalleled impact on the education, formation and mental state of the cardiologists in training. Regulatory agencies, universities and politicians should make a great effort in the organization and reorganization of the teaching programs of the cardiologists of tomorrow.

Background Adverse cardiac remodeling is a major risk factor for the development of post myocardial infarction (MI) heart failure (HF). This study investigates the effects of the chymase inhibitor fulacimstat on adverse cardiac remodeling after acute ST-segment-elevation myocardial infarction (STEMI). Methods In this double-blind, randomized, placebo-controlled trial patients with first STEMI were eligible. To preferentially enrich patients at high risk of adverse remodeling, main inclusion criteria were a left-ventricular ejection fraction (LVEF) ≤45% and an infarct size >10% on day 5 to 9 post MI as measured by cardiac MRI. Patients were then randomized to 6 months treatment with either 25 mg fulacimstat (n = 54) or placebo (n = 53) twice daily on top of standard of care starting day 6 to 12 post MI. The changes in LVEF, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume index (LVESVI) from baseline to 6 months were analyzed by a central blinded cardiac MRI core laboratory. Results Fulacimstat was safe and well tolerated and achieved mean total trough concentrations that were approximately tenfold higher than those predicted to be required for minimal therapeutic activity. Comparable changes in LVEF (fulacimstat: 3.5% ± 5.4%, placebo: 4.0% ± 5.0%, P = .69), LVEDVI (fulacimstat: 7.3 ± 13.3 mL/m2, placebo: 5.1 ± 18.9 mL/m2, P = .54), and LVESVI (fulacimstat: 2.3 ± 11.2 mL/m2, placebo: 0.6 ± 14.8 mL/m2, P = .56) were observed in both treatment arms. Conclusion Fulacimstat was safe and well tolerated in patients with left-ventricular dysfunction (LVD) after first STEMI but had no effect on cardiac remodeling.

Aims: Heart failure (HF) affects approximately 26 million people worldwide. With an aging global population, innovative approaches to HF evaluation and management are needed to cope with the worsening HF epidemic. The aim of the Real-Life Multimarker Monitoring in Patients with Heart Failure (REALIsM-HF) study (NCT03507439) is to evaluate a composite instrument comprising remote, real-time, activity-monitoring devices combined with daily electronic patient-reported outcome (ePRO) items in patients who have been hospitalized for HF and are undergoing standard HF assessment (e.g., 6-min walking distance [6MWD], blood biomarkers, Kansas City Cardiomyopathy Questionnaire [KCCQ], and echocardiography). Methods: REALIsM-HF is an ongoing, 12-week, observational study enrolling 80–100 patients aged ≥45 years with HF with preserved ejection fraction (HFpEF; EF ≥45%) or reduced EF (HFrEF; EF ≤35%). Statistical analyses will include examining the association between data from wearables (the AVIVO© mobile patient management patch or VitalPatch© biosensor, and the DynaPort MoveMonitor©), daily ePROs, and conventional HF metrics (e.g., serum/plasma biomarkers, 6MWD, KCCQ, and echocardiographic parameters). The feasibility of and patient compliance with at-home devices will be documented, and the data captured for the purpose of establishing reference values in patients with HFpEF or HFrEF will be summarized. Conclusions: The REALIsM-HF study is to evaluate the longitudinal daily activity profiles of patients with HF and correlate these with changes in serum/plasma biomarker profiles, symptoms, quality of life, and cardiac function and morphology to inform the use of wearable activity monitors for developing novel therapies and managing patients.

Aims To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy. Methods and results The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020. Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease. Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease. Mean age was 67 ± 12 years, and 80 (81%) patients were males. No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients. During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock. Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08–5.09). The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively). Conclusions Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.

Sacubitril/valsartan improves outcome in patients with heart failure (HF) with reduced left ventricular (LV) ejection fraction (EF, HFrEF). However, little is known about possible mechanisms underlying this favourable effect.To assess changes in echocardiographically-derived hemodynamic profiles induced by sacubitril/valsartan and their impact on outcome.In this multicenter, open-label study, 727 HFrEF outpatients underwent comprehensive echocardiography at baseline (before starting sacubitril/valsartan) and after 12 months. Estimated LV filling pressure (E/e') and cardiac index (CI, l/min/mAt baseline, 29% had profile-A, 15% had profile-B, 32% profile-C, and 24% profile-D. After 12 months, the hemodynamic profile improved in 53% of patients (all profile-A achievers, or profile-D patients achieving either C or B profile), while it remained unchanged in 39% patients and worsened in 9%. Prevalence of improved profile progressively increased with increasing dose of sacubitril/valsartan (P 0.0001). After the second echocardiography, patients were followed up 12.6 ± 7.6 months: event-rate was lower in patients with improved profile (12.3%, 95%CI: 9.4-16.1) compared to patients in whom hemodynamic profile remained unchanged (29.9%, 24.0-37.3) or worsened (31.2%, 20.7-46.9, P 0.0001). Improved hemodynamic profile was associated with favourable outcome independent of LVEF and other covariates (HR 0.65, 95%CI: 0.45-0.95, P 0.05).In HFrEF patients, the beneficial prognostic effects of sacubitril/valsartan are associated with improvement in hemodynamic conditions.

Every human being possesses an exclusive nutritional blueprint inside their genes. Bioactive food components and nutrients affect the expression of such genes. Nutrigenomics is the science that analyzes gene-nutrient interactions (nutrigenetics), which can lead to the development of personalized nutritional recommendations to maintain optimal health and prevent disease. Genomic diversity among various ethnic groups might affect nutrients bioavailability as well as their metabolism. Nutrigenomics combines different branches of science including nutrition, bioinformatics, genomics, molecular biology, molecular medicine, and epidemiology. Genes regulate intake and metabolism of different nutrients, while nutrients positively or negatively influence the expression of a number of genes; testing of specific genetic polymorphisms may therefore become a useful tool to manage weight loss and to fully understand gene-nutrient interactions. Indeed, several approaches are used to study gene-nutrient interactions: epigenetics, the study of genome modification not related to changes in nucleotide sequence; transcriptomics, the study of tissue-specific and time-specific RNA transcripts; proteomics, the study of proteins involved in biological processes; and metabolomics, the study of changes of primary and secondary metabolites in body fluids and tissues. Hence, the use of nutrigenomics to improve and optimize a healthy, balanced diet in clinical settings could be an effective approach for long-term lifestyle changes that might lead to consistent weight loss and improve quality of life., Journal of Preventive Medicine and Hygiene, Vol. 63 No. 2S3 (2022): The secret of Mediterranean food: How “omic” sciences, biochemistry and human physiology can be applied to exploit the secrets of Mediterranean foods

Renin-angiotensin-aldosterone system (RAAS) inhibition is a mainstay of the pharmacological treatment of heart failure with reduced ejection fraction (HFrEF). In the last years RAAS blockade has been improved by the introduction of the Angiotensin Receptor-Neprilysin Inhibitor (ARNI) sacubitril/valsartan, that combines RAAS inhibition with the block of neprilysin, boosting the positive effects of natriuretic peptides. The PARADIGM-HF trial demonstrated a significant advantage of sacubitril/valsartan over enalapril on the reduction of cardiovascular (CV) mortality and heart failure hospitalizations rates. Then, several randomized clinical trials and observational studies investigated its role in different clinical settings and its efficacy has been fully recognized in the most recent HFrEF European and USA guidelines. The effects of sacubitril/valsartan on major CV outcomes are associated with reduction of NT-proBNP levels and reverse cardiac remodeling and mitral regurgitation, recognized as one of the mechanistic effects of the drug explaining the favorable prognostic effects. A careful evaluation of patients' clinical profile is relevant to implement the use of ARNI in the clinical practice and to obtain the maximal treatment efficacy. The present Position Paper reports the opinion of the Italian Society of Cardiology on the optimal blockade of the RAAS system in HF patients with the aim of fostering widespread implementation of scientific evidence and practice guidelines in the medical community.

Accurate nutritional assessment based on dietary intake, physical activity, genetic makeup, and metabolites is required to prevent from developing and/or to treat people suffering from malnutrition as well as other nutrition related health issues. Nutritional screening ought to be considered as an essential part of clinical assessment for every patient on admission to healthcare setups, as well as on change in clinical conditions. Therefore, a detailed nutritional assessment must be performed every time nutritional imbalances are observed or suspected. In this review we have explored different techniques used for nutritional and physical activity assessment. Dietary Intake (DI) assessment is a multidimensional and complex process. Traditionally, dietary intake is assessed through self-report techniques, but due to limitations like biases, random errors, misestimations, and nutrient databases-linked errors, questions arise about the adequacy of self-reporting dietary intake procedures. Despite the limitations in assessing dietary intake (DI) and physical activity (PA), new methods and improved technologies such as biomarkers analysis, blood tests, genetic assessments, metabolomic analysis, DEXA (Dual-energy X-ray absorptiometry), MRI (Magnetic resonance imaging), and CT (computed tomography) scanning procedures have made much progress in the improvement of these measures. Genes also plays a crucial role in dietary intake and physical activity. Similarly, metabolites are also involved in different nutritional pathways. This is why integrating knowledge about the genetic and metabolic markers along with the latest technologies for dietary intake (DI) and physical activity (PA) assessment holds the key for accurately assessing one’s nutritional status and prevent malnutrition and its related complications., Journal of Preventive Medicine and Hygiene, Vol. 63 No. 2S3 (2022): The secret of Mediterranean food: How “omic” sciences, biochemistry and human physiology can be applied to exploit the secrets of Mediterranean foods

Early epidemiologic studies in type 2 diabetes suggested that the long-term risk of microvascular and macrovascular complications increase progressively as glucose concentrations rise, inspiring the pursuit of near euglycaemia as a means of preventing these complications in type 1 and type 2 diabetes. Evidence emerging over the past decade, however, showed that the aggressive efforts often needed to achieve low HbA1c levels can ultimately lead to worse clinical outcomes, greater risk of severe hypoglycaemia, and higher burden of treatment. The acknowledgment of the disappointing results obtained with therapies aimed exclusively at improving glycaemic control has led in recent years to a substantial paradigm shift in the treatment of the diabetic patient. The results obtained first with GLP-1RAs and more recently even more with SGLT2i on mortality and CV events have made it clear how other mechanisms, beyond the hypoglycaemic effect, are at the basis of the benefits observed in several cardiovascular outcome trials. And as evidence of the great revolution of thought we are experiencing, there is the recognition of gliflozins as drugs for the treatment not only of diabetic patients but also of non-diabetic patients suffering from HF, as reported in the latest ESC/HFA guidelines. Surely, we still have a lot to understand, but it is certain that this is the beginning of a new era.

Aims Sodium glucose cotransporter type 2 (SGLT2) inhibitors represent a new class of hypoglycemic agents for type 2 diabetes mellitus (T2DM), which act independently of insulin to selectively inhibit renal glucose reabsorption, thereby increasing urinary excretion of glucose. Several studies have demonstrated the cardioprotective effects of SGLT2-i in patients with heart failure (HF), with and without diabetes mellitus. It is also unknown whether these SGLT2is-associated benefits are associated with the amelioration of left or right ventricular function in patients affected by HF with T2DM. Evaluate the effect of SGLT2 inhibitors on left and right ventricular function by conventional and advanced echocardiographic parameters, focusing on speckle tracking echocardiography, in patients with HF and T2DM. Methods and results BEGIN-HF is an international multi-centre registry enrolling outpatients affected by HF and T2DM. Inclusion criteria are HbA1c> 6.5%, eGFR [MDRD] > 45 ml/min/1.73 m2, age > 18 years, FE Conclusions This is the first international multicentre registry evaluating biventricular function by conventional and advanced echocardiography in patients with HF and T2DM starting and no-starting SGLT2i therapy.

Background During the lockdown period in Italy, from March 11th to May 4th 2020, a progressive increase in COVID-19 cases occurred in all Italian regions, in particular in the Lombardy Region. The current rise in COVID-19 cases has led to an increasing involvement of hospitals, in order to face the Coronavirus outbreak, shifting healthcare resources towards the management of COVID+ patients. This has led, on the other hand, to a progressive decrease in hospital admissions due to conditions not associated with SARS-CoV2 infection. During COVID-19 outbreak period, it has been observed a decrease in hospital admissions for acute myocardial infarction. This phenomenon put in serious difficulty the clinical management of COVID-free patients with cardiovascular disease, at the beginning of phase 2 (starting from May 4 2020). Purpose In this scenario, we aimed to verify the impact of telemedicine during lockdown, in comparison with the same period in 2019. Materials and method We analyzed 12-lead ECGs recorded by 5000 country pharmacies, evaluated and stored in one telemedicine platform provided by Health Telematic Network (HTN), in cooperation with our Cardiology Department, Federfarma (Pharmacists' National Association), and Italian National Health Institute. Results During the lockdown period, were recorded 6,104 ECGs in territorial pharmacies, compared to 17,280 ECGs done in the same period in 2019. Chest pain symptom represented the cause of recording ECG in 298 patients (4.88%) during the lockdown period, compared to 402 patients (2.33%) in the same period in 2019, with an increase of 109.86%. In the Lombardy Region, during lockdown period, were reported 118 accesses to territorial pharmacies for chest pain (about 39.50% of total cases in Italy). Among these, 36 accesses were in the province of Brescia (about 30.50%), whereas 28 of them were in the province of Bergamo (about 23.73%). Among ECGs performed, 8 showed typical abnormalities of acute myocardial infarction with ST elevation (STEMI, 2.68%) in the lockdown period, compared to 7 STEMIs (1.74%) detected in the same period in 2019, with an increase of 54.17%. These patients were referred to Emergency Department (ED) suddenly, for the therapeutic intervention. Conclusion These data shown that a large number of patients with cardiovascular symptoms preferred to go to territorial pharmacies rather than hospitals during the COVID outbreak period. Telemedicine played a prominent role in managing patients with cardiovascular symptoms at home. Moreover, this service allowed patients with STEMI to access to the hospitals faster, avoiding the risks of a serious diagnostic delay. Furthermore, by analyzing the data of Lombardy Region, it was possible to show how a significant component of access to local pharmacies for chest pain occurred in the region most affected by the COVID-19 outbreak. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): University of Brescia Number of ECGs recorded for chest painData recorded in Lombardy Region

Purpose of Review The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in the regulation of cardiovascular function, and it is disrupted in heart failure (HF), resulting in decreased protection against myocardial injury. Impaired NO-sGC-cGMP signaling in HF is secondary to reduced NO bioavailability and altered redox state of sGC, which becomes less responsive to NO. The sGC activator cinaciguat increases cGMP levels by direct NO-independent activation of sGC and may be particularly effective in conditions of increased oxidative stress and endothelial dysfunction, and therefore reduced NO levels, at the expense of a greater risk of hypotension. Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, thus exerting a more physiological action. Recent Findings Clinical trials have suggested the benefit of vericiguat in patients with high-risk HF; in particular, a lower incidence of death from cardiovascular causes or HF hospitalization. Summary Adding vericiguat may be considered in individual patients with HF, and reduced left ventricular ejection fraction (HFrEF) particularly those at higher risk of HF hospitalization.

The chymase inhibitor fulacimstat is developed as a first-in-class treatment option for the inhibition of adverse cardiac remodeling in patients with left ventricular dysfunction (LVD) after acute myocardial infarction (MI). The aim of the study was to examine the safety and tolerability of fulacimstat in patients with LVD after remote MI. A multicenter, multinational randomized, placebo-controlled study was performed in clinically stable patients (40–79 years of age, left ventricular ejection fraction ≤ 45% because of MI in medical history) who were on stable evidence-based standard-of-care therapies for LVD post-MI including an angiotensin converting enzyme inhibitor or angiotensin receptor blocker at doses of at least half the recommended target dose. Patients were treated for 2 weeks with either placebo (n = 12) or 4 different doses of fulacimstat (5 mg twice daily, n = 9; 10 mg twice daily, n = 9; 25 mg twice daily, n = 10; 50 mg once daily, n = 9). Fulacimstat was safe and well tolerated at all examined doses. There were no clinically relevant effects on vital signs or potassium levels compared with placebo treatment. Mean plasma concentrations of fulacimstat increased with the administered dose and reached exposures predicted to be therapeutically active. The safety profile and the absence of effects on blood pressure or heart rate in a chronic patient population having similar comorbidities and receiving similar comedication as patients after acute MI support future clinical trials with fulacimstat in patients after acute MI.

Despite recent advances in chronic heart failure management (either pharmacological or non-pharmacological), the prognosis of heart failure (HF) patients remains poor. This poor prognosis emphasizes the need for developing novel pathways for testing new HF drugs, beyond neurohumoral and hemodynamic modulation approaches. The development of new drugs for HF therapy must thus necessarily focus on novel approaches such as the direct effect on cardiomyocytes, coronary microcirculation, and myocardial interstitium. This review summarizes principal evidence on new possible pharmacological targets for the treatment of HF patients, mainly focusing on microcirculation, cardiomyocyte, and anti-inflammatory therapy.

The current COVID-19 pandemic has renewed interest in providing healthcare services based on the implementation of innovative technologies. Such strategy capillarizes the therapeutic opportunities for larger urban areas, mostly when people are living under extraordinarily difficult circumstances. Improving care delivery in cardiovascular diseases appears particularly feasible when telemedicine is pursued, especially with regard to baseline standard 12-lead electrocardiography, ambulatory electrocardiographic monitoring, and 24-hour ambulatory blood pressure monitoring. Nowadays, these first-line cardiovascular examinations are also available in health centers and pharmacies, and in recent months, there has been an increasing demand of such local services in the absence of specific rules and regulations regarding technical requirements and standards of interpretation that ensure a high quality clinical consultation.The purpose of this position paper is to provide critical requirements for the type/model of devices to be used, training dedicated to healthcare personnel, ensuring security of sensitive data, highlighting type of platforms to be used, as well as for maintaining high reporting quality and standards.

The coronavirus disease (COVID-19) pandemic has caused 2.69 million deaths and 122 million infections. Great efforts have been made worldwide to promptly develop effective vaccines and reduce morbidity and mortality rates from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Available vaccines have proven highly effective at preventing symptomatic disease in clinical trials and real-world reports and are playing an essential role in flattening the epidemiology curve and, mostly, in reducing COVID-19 hospitalizations. Some concerns have been raised after very rare cases of myocarditis and pericarditis recently reported by the Centers for Disease Control and Prevention (CDC) as potentially associated with COVID-19 mRNA vaccinations, namely the Pfizer-BioNTech mRNA vaccine (BNT162b2) and the Moderna mRNA vaccine (mRNA-1273). Therefore, the aim of this document is to explore the possible link between COVID-19 mRNA vaccination and the development of myocarditis and/or pericarditis by performing a critical analysis of available data and to provide indications for specific subgroups of individuals.