Gender Effect on Clinical Profiles, Pharmacological Treatments and Prognosis in Patients Hospitalized for Heart Failure.

Heart failure (HF) is a significant disease affecting 1-2% of the general population. Despite its general aspects, HF, like other cardiovascular diseases, presents various gender-specific aspects in terms of etiology, hemodynamics, clinical characteristics, therapy, and outcomes. As is well known, HF with preserved ejection fraction more frequently affects females, with diabetes and arterial hypertension representing the most critical determinants of HF. On the other hand, women are traditionally underrepresented in clinical trials and are often considered undertreated. However, it is not clear whether such differences reflect cultural behaviors and clinical inertia or if they indicate different clinical profiles and the impact of sex on hard clinical outcomes. We aimed to review the sex-related differences in patients affected by HF.

Right Ventricular Subclinical Dysfunction in SLE Patients Correlates with Metabolomic Fingerprint and Organ Damage.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease, and several studies have suggested possible early RV involvement. Aim of the study was to evaluate the 3D echo parameters of the right ventricle (RV) and the metabolomic profile to correlate both with SLE severity. Forty SLE patients, free of cardiovascular disease, were enrolled and the following 3D parameters were evaluated: the RV ejection fraction (RV-EF), longitudinal strain of the interventricular septum (Septal LS), longitudinal strain of the free wall (Free-LS) and the fractional area change (FAC). In addition, a metabolomic analysis was performed. Direct correlations were observed between TAPSE values and the RV 3D parameters. Then, when splitting the population according to the SDI value, it was found that patients with higher cumulative damage (≥3) had significantly lower FAC, RV-EF, Septal LS, and Free-LS values; the latter three parameters showed a significant correlation with the metabolic profile of the patients. Furthermore, the division based on SDI values identified different metabolic profiles related to the degree of RV dysfunction. The RV dysfunction induced by the chronic inflammatory state present in SLE can be identified early by 3D echocardiography. Its severity seems to be related to systemic organ damage and the results associated with a specific metabolic fingerprint constituted by 2,4-dihydroxybutyric acid, 3,4-dihydroxybutyric acid, citric acid, glucose, glutamine, glycine, linoleic acid, oleic acid, phosphate, urea, and valine.

Cardiovascular prevention in childhood: a consensus document of the Italian Society of Cardiology Working Group on Congenital Heart Disease and Cardiovascular Prevention in Paediatric Age.

Cardiovascular diseases (CVD) may be manifested from a very early age. Genetic and environmental (epigenetic) factors interact to affect development and give rise to an abnormal phenotypical expression of genetic information, although not eliciting changes in the nucleotide sequence of DNA. It has been scientifically proven that increased oxidative stress (OS) caused by disease (overweight, obesity, diabetes), nutritional imbalances, unhealthy lifestyles (smoking, alcohol, substance abuse) in the mother during pregnancy may induce placental dysfunction, intrauterine growth restriction, prematurity, low birth weight, postnatal adiposity rebound, metabolic alterations and consequent onset of traditional cardiovascular risk factors. OS represents the cornerstone in the onset of atherosclerosis and manifestation of CVD following an extended asymptomatic period. OS activates platelets and monocytes eliciting the release of pro-inflammatory, pro-atherogenic and pro-oxidising substances resulting in endothelial dysfunction, decrease in flow-mediated arterial dilatation and increase in carotid intima-media thickness. The prevention of CVD is defined as primordial (aimed at preventing risk factors development), primary (aimed at early identification and treatment of risk factors), secondary (aimed at reducing risk of future events in patients who have already manifested a cardiovascular event), and tertiary (aimed at limiting the complex outcome of disease). Atherosclerosis prevention should be implemented as early as possible. Appropriate screening should be carried out to identify children at high risk who are apparently healthy and implement measures including dietary and lifestyle changes, addition of nutritional supplements and, lastly, pharmacological treatment if risk profiles fail to normalise. Reinstating endothelial function during the reversible stage of atherosclerosis is crucial.

The gray areas of oral anticoagulation for prevention of thromboembolic events in atrial fibrillation patients.

Thromboembolic events (TEE) associated with atrial fibrillation (AF) are highly recurrent and usually severe, causing permanent disability or, even, death. Previous data consistently showed significantly lower TEE in anticoagulated patients. While warfarin, a vitamin K antagonist, is still used worldwide, direct-acting oral anticoagulants (DOACs) have shown noninferiority to warfarin in the prevention of TEE, and represent, to date, the preferred treatment. DOACs present favorable pharmacokinetic, safety and efficacy profiles, especially among vulnerable patients including the elderly, those with renal dysfunction or previous TEE. Yet, regarding specific settings of AF patients it is unclear whether oral anticoagulation therapy is beneficial, or otherwise it is the maintenance of sinus rhythm, mostly achieved through a catheter ablation-based rhythm control strategy, that prevents the causal complications linked to AF. While it is known that low-risk patients [CHA2DS2-VASc 0 (males), or score of 1 (females)] present low ischemic stroke or mortality rates (<1%/year), it remains unclear whether they need any prophylaxis. Furthermore, the appropriate anticoagulation regimen for those individuals requiring cardioversion, either pharmacologic or electric, as well as peri-procedural anticoagulation in patients undergoing trans-catheter ablation that nowadays encompasses different energies, are still a matter of debate. In addition, AF concomitant with other clinical conditions is discussed and, lastly, the choice of prescribing anticoagulation to asymptomatic patients diagnosed with subclinical AF at either wearable or implanted devices. The aim of this review will be to provide an update on current strategies in the above-mentioned settings, and to suggest possible therapeutic options, finally focusing on AF-related cognitive decline.

Evolving concepts in the pathophysiology of atherosclerosis: from endothelial dysfunction to thrombus formation through multiple shades of inflammation.

Atherosclerosis is the anatomo-pathological substrate of most cardio, cerebro and vascular diseases such as acute and chronic coronary syndromes, stroke and peripheral artery diseases. The pathophysiology of atherosclerotic plaque and its complications are under continuous investigation. In the last 2 decades our understanding on the formation, progression and complication of the atherosclerotic lesion has greatly improved and the role of immunity and inflammation is now well documented and accepted. The conventional risk factors modulate endothelial function determining the switch to a proatherosclerotic phenotype. From this point, lipid accumulation with an imbalance from cholesterol influx and efflux, foam cells formation, T-cell activation, cytokines release and matrix-degrading enzymes production occur. Lesions with high inflammatory rate become vulnerable and prone to rupture. Once complicated, the intraplaque thrombogenic material, such as the tissue factor, is exposed to the flowing blood, thus inducing coagulation cascade activation, platelets aggregation and finally intravascular thrombus formation that leads to clinical manifestations of this disease. Nonconventional risk factors, such as gut microbiome, are emerging novel markers of atherosclerosis. Several data indicate that gut microbiota may play a causative role in formation, progression and complication of atherosclerotic lesions. The gut dysbiosis-related inflammation and gut microbiota-derived metabolites have been proposed as the main working hypothesis in contributing to disease formation and progression. The current evidence suggest that the conventional and nonconventional risk factors may modulate the degree of inflammation of the atherosclerotic lesion, thus influencing its final fate. Based on this hypothesis, targeting inflammation seems to be a promising approach to further improve our management of atherosclerotic-related diseases.

Speckle tracking echocardiography in early disease stages: a therapy modifier?

Echocardiography has been included as a first-line tool in several international guidelines for the management of patients with various cardiac diseases. Beyond diagnosis, echocardiographic examination helps in characterizing the severity of the condition since the very first stages. In particular, the application of second-level techniques, speckle tracking echocardiography in particular, can also reveal a subclinical dysfunction, while the standard parameters are in the normality range. The present review describes the potentialities of advanced echocardiography in different settings, including arterial hypertension, atrial fibrillation, diastolic dysfunction, and oncological patients, thus opening up potential starting points for its application as a clinical routine changer.

Computed tomography and nuclear medicine for the assessment of coronary inflammation: clinical applications and perspectives.

There is increasing evidence that in patients with atherosclerotic cardiovascular disease (ASCVD) under optimal medical therapy, a persisting dysregulation of the lipid and glucose metabolism, associated with adipose tissue dysfunction and inflammation, predicts a substantial residual risk of disease progression and cardiovascular events. Despite the inflammatory nature of ASCVD, circulating biomarkers such as high-sensitivity C-reactive protein and interleukins may lack specificity for vascular inflammation. As known, dysfunctional epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT) produce pro-inflammatory mediators and promote cellular tissue infiltration triggering further pro-inflammatory mechanisms. The consequent tissue modifications determine the attenuation of PCAT as assessed and measured by coronary computed tomography angiography (CCTA). Recently, relevant studies have demonstrated a correlation between EAT and PCAT and obstructive coronary artery disease, inflammatory plaque status and coronary flow reserve (CFR). In parallel, CFR is well recognized as a marker of coronary vasomotor function that incorporates the haemodynamic effects of epicardial, diffuse and small-vessel disease on myocardial tissue perfusion. An inverse relationship between EAT volume and coronary vascular function and the association of PCAT attenuation and impaired CFR have already been reported. Moreover, many studies demonstrated that 18F-FDG PET is able to detect PCAT inflammation in patients with coronary atherosclerosis. Importantly, the perivascular FAI (fat attenuation index) showed incremental value for the prediction of adverse clinical events beyond traditional risk factors and CCTA indices by providing a quantitative measure of coronary inflammation. As an indicator of increased cardiac mortality, it could guide early targeted primary prevention in a wide spectrum of patients. In this review, we summarize the current evidence regarding the clinical applications and perspectives of EAT and PCAT assessment performed by CCTA and the prognostic information derived by nuclear medicine.

Innovations in medical therapy of heart failure with reduced ejection fraction.

Heart failure with reduced ejection fraction (HFrEF) is a pathological condition still characterized by high rates of mortality and disease exacerbation frequently leading to hospitalization, thus there is a continuous need for pharmacological treatments impacting on disease stability and long-term prognosis. Moreover, the phenotype of heart failure patients is continuously changing over time, and the development of new heart failure drugs is crucial to promote a personalized and targeted approach. In recent years, several therapeutic innovations have emerged in the landscape of acute and chronic HFrEF, largely changing and improving our approach to the disease. Various studies on new drugs and experimental therapeutic approaches are ongoing. The present review discusses the latest data on both recently approved drugs and developing therapeutic targets, in order to provide a critical overview for an informed and optimal approach to such a complex disease.

Impact of COVID-19 on the cardiovascular health of women: a review by the Italian Society of Cardiology Working Group on 'gender cardiovascular diseases'.

The coronavirus disease 19 (COVID-19), due to coronavirus 2 (SARS-CoV-2) infection, presents with an extremely heterogeneous spectrum of symptoms and signs. COVID-19 susceptibility and mortality show a significant sex imbalance, with men being more prone to infection and showing a higher rate of hospitalization and mortality than women. In particular, cardiovascular diseases (preexistent or arising upon infection) play a central role in COVID-19 outcomes, differently in men and women. This review will discuss the potential mechanisms accounting for sex/gender influence in vulnerability to COVID-19. Such variability can be ascribed to both sex-related biological factors and sex-related behavioural traits. Sex differences in cardiovascular disease and COVID-19 involve the endothelial dysfunction, the innate immune system and the renin-angiotensin system (RAS). Furthermore, the angiotensin-converting enzyme 2 (ACE2) is involved in disease pathogenesis in cardiovascular disease and COVID-19 and it shows hormone-dependent actions. The incidence of myocardial injury during COVID-19 is sex-dependent, predominantly in association with a greater degree of inflammation and coagulation disorders among men. Its pathogenesis is not fully elucidated, but the main theories foresee a direct role for the ACE2 receptor, the hyperimmune response and the RAS imbalance, which may also lead to isolated presentation of COVID-19-mediated myopericarditis. Moreover, the latest evidence on cardiovascular diseases and their relationship with COVID-19 during pregnancy will be discussed. Finally, authors will analyse the prevalence of the long-covid syndrome between the two sexes and its impact on the quality of life and cardiovascular health.

Gender Differences and Cardiometabolic Risk: The Importance of the Risk Factors.

Metabolic syndrome (Mets) is a clinical condition characterized by a cluster of major risk factors for cardiovascular disease (CVD) and type 2 diabetes: proatherogenic dyslipidemia, elevated blood pressure, dysglycemia, and abdominal obesity. Each risk factor has an independent effect, but, when aggregated, they become synergistic, doubling the risk of developing cardiovascular diseases and causing a 1.5-fold increase in all-cause mortality. We will highlight gender differences in the epidemiology, etiology, pathophysiology, and clinical expression of the aforementioned Mets components. Moreover, we will discuss gender differences in new biochemical markers of metabolic syndrome and cardiovascular risk.

Metabolomic Profiles on Antiblastic Cardiotoxicity: New Perspectives for Early Diagnosis and Cardioprotection.

Antiblastic drugs-induced cardiomyopathy remains a relevant cause of morbidity and mortality, during and after chemotherapy, despite the progression in protective therapy against cardiovascular diseases and myocardial function. In the last few decades, many groups of researchers have focused their attention on studying the metabolic profile, first in animals, and, subsequently, in humans, looking for profiles which could be able to predict drug-induced cardiotoxicity and cardiovascular damage. In clinical practice, patients identified as being at risk of developing cardiotoxicity undergo a close follow-up and more tailored therapies. Injury to the heart can be a consequence of both new targeted therapies, such as tyrosine kinase inhibitors, and conventional chemotherapeutic agents, such as anthracyclines. This review aims to describe all of the studies carried on this topic of growing interest.

[Italian Society of Cardiology-Italian Society of Nephrology Consensus document: The cardio-renal interaction in the prevention and treatment of cardiovascular diseases - Part II: From preventive strategies to treatment of patients with cardio-renal damage]. / Documento di consenso Società Italiana di Cardiologia- Società Italiana di Nefrologia: Ruolo dell'asse cardio-renale nella prevenzione e trattamento delle patologie cardiovascolari ­ Parte II: Dalle strategie di prevenzione al trattamento del paziente con coinvolgimento cardio-renale.

Chronic kidney disease and cardiovascular disease are strictly connected each other with a bidirectional interaction. Thus, the prevention of cardio-renal damage, as its appropriate treatment, are essential steps for a correct management of long-term patients' prognosis. Several preventive and therapeutic strategies, pharmacological and not, are now available for cardio-renal damage prevention and treatment, and for the management of its complications. The second part of this consensus document focuses on the management and treatment of cardio-renal damage, directing the attention on the correct use of drugs that may slow renal disease progression, on the application of preventive strategies in case of invasive cardiac procedures with the use of contrast agents, and on the accurate use of cardiological drugs in patients with chronic kidney disease.

[Italian Society of Cardiology-Italian Society of Nephrology Consensus document: The cardio-renal interaction in the prevention and treatment of cardiovascular diseases - Part I: From cardiovascular risk factors to the mechanisms of cardio-renal syndrome]. / Documento di consenso Società Italiana di Cardiologia- Società Italiana di Nefrologia: Ruolo dell'asse cardio-renale nella prevenzione e trattamento delle patologie cardiovascolari ­ Parte I: Dai fattori di rischio cardiovascolare ai meccanismi di danno cardio-renale.

Chronic kidney disease (CKD) and cardiovascular (CV) disease are highly prevalent conditions in the general population and are strictly connected to each other with a bidirectional interaction. In patients affected by CKD, the leading cause of morbidity and mortality is represented by CV disease, since CKD promotes the atherosclerotic process increasing inflammation, and modifying lipid and bone mineral metabolism. On the other side, a strict relationship exists between CKD and CV risk factors, which are prevalent in nephropathic patients and impose a stringent assessment of the risk of CV events in this population together with an optimized pharmacological approach, complicated by the coexistence of the two pathological conditions. The first part of this consensus document focuses on the mechanisms of cardio-renal damage and on the impact, as well as the management, of the main CV risk factors in the context of CKD.

[2022 Update on myocarditis and pericarditis following COVID-19 vaccination. Expert Opinion of the Italian Society of Cardiology]. / Update 2022 dell'Expert Opinion della Società Italiana di Cardiologia su miocarditi, pericarditi e vaccini contro il COVID-19.

Vaccine-associated myocarditis and pericarditis usually develop within 14 days of COVID-19 vaccination, are exceptionally rare, manifest with mild clinical pictures and are commonly characterized by a favorable evolution. Young men inoculated with two doses of an mRNA vaccine are the subgroup at higher risk. Recent epidemiological studies evaluated the incidence and risk of vaccine-associated myocarditis and pericarditis among men and women, in different ranges of age and specific types of vaccines. Long-term population analyses demonstrated that the cardiovascular risk conferred by COVID-19 extends beyond the acute phase, representing the rationale for implementing prevention strategies for SARS-CoV-2 infection, monitoring specific populations at higher risk and pursuing the completion of the vaccination campaign. This document provides an update on the most recent scientific evidence and critical interpretation of available data in constant evolution towards personalized strategies of immunization.

[Italian Society of Cardiology (SIC) Expert consensus document: Post-acute cardiovascular sequelae of SARS-CoV-2 infection]. / Expert consensus document della Società Italiana di Cardiologia (SIC): Sequele cardiovascolari post-acute dell'infezione da SARS-CoV-2.

Although the clinical course of COVID-19 in its acute phase is now delineated, less known is its late phase characterized by a heterogeneous series of sequelae affecting various organs and systems, including the cardiovascular system, which continue after the acute episode or arise after their resolution. This syndrome, now referred with the new acronym "PASC" (post-acute sequelae of SARS-CoV-2 infection) has been formally recognized by various scientific societies and international organizations that have proposed various definitions. The World Health Organization defines PASC, distinguishing it from "ongoing symptomatic COVID-19", as a condition that arises few weeks after infection, persists at least 8 weeks, and cannot be explained by alternative diagnoses.There are multiple mechanisms responsible for PASC: inflammation, immune activation, viral persistence, activation of latent viruses, endothelial dysfunction, impaired response to exercise, and profound cardiac deconditioning following viral infection. The key symptoms of PASC are palpitations, effort dyspnea, chest pain, exercise intolerance, and postural orthostatic tachycardia syndrome.For PASC treatment, it may be useful to take salt and fluid loading, to reduce symptoms such as tachycardia, palpitations, and/or orthostatic hypotension, or in some subjects the use of drugs such as beta-blockers, non-dihydropyridine calcium channel blockers, ivabradine, and fludrocortisone.Finally, in PASC a gradual resumption of physical activity is recommended, starting with recumbent or semi-recumbent exercise, such as cycling, swimming, or rowing, and then moving on to exercise in an upright position such as running when the ability to stand improves without dyspnea appearance. Exercise duration should also be short initially (5 to 10 min per day), with gradual increases as functional capacity improves.

Appropriateness criteria for the use of cardiac computed tomography, SIC-SIRM part 2: acute chest pain evaluation; stent and coronary artery bypass graft patency evaluation; planning of coronary revascularization and transcatheter valve procedures; cardiomyopathies, electrophysiological applications, cardiac masses, cardio-oncology and pericardial diseases evaluation.

In the past 20 years, cardiac computed tomography (CCT) has become a pivotal technique for the noninvasive diagnostic workup of coronary and cardiac diseases. Continuous technical and methodological improvements, combined with fast growing scientific evidence, have progressively expanded the clinical role of CCT. Randomized clinical trials documented the value of CCT in increasing the cost-effectiveness of the management of patients with acute chest pain presenting in the emergency department, also during the pandemic. Beyond the evaluation of stents and surgical graft patency, the anatomical and functional coronary imaging have the potential to guide treatment decision-making and planning for complex left main and three-vessel coronary disease. Furthermore, there has been an increasing demand to use CCT for preinterventional planning in minimally invasive procedures, such as transcatheter valve implantation and mitral valve repair. Yet, the use of CCT as a roadmap for tailored electrophysiological procedures has gained increasing importance to assure maximum success. In the meantime, innovations and advanced postprocessing tools have generated new potential applications of CCT from the simple coronary anatomy to the complete assessment of structural, functional and pathophysiological biomarkers of cardiac disease. In this complex and revolutionary scenario, it is urgently needed to provide an updated guide for the appropriate use of CCT in different clinical settings. This manuscript, endorsed by the Italian Society of Cardiology (SIC) and the Italian Society of Medical and Interventional Radiology (SIRM), represents the second of two consensus documents collecting the expert opinion of cardiologists and radiologists about current appropriate use of CCT.

Cardiovascular Risk Perception and Knowledge among Italian Women: Lessons from IGENDA Protocol.

A multicenter, cross-sectional observational study (Italian GENder Differences in Awareness of Cardiovascular risk, IGENDA study) was carried out to evaluate the perception and knowledge of cardiovascular risk among Italian women. An anonymous questionnaire was completed by 4454 women (44.3 ± 14.1 years). The 70% of respondents correctly identified cardiovascular disease (CVD) as the leading cause of death. More than half of respondents quoted cancer as the greatest current and future health problem of women of same age. Sixty percent of interviewed women considered CVD as an almost exclusively male condition. Although respondents showed a good knowledge of the major cardiovascular risk factors, the presence of cardiovascular risk factors was not associated with higher odds of identifying CVD as the biggest cause of death. Less than 10% of respondents perceived themselves as being at high CVD risk, and the increased CVD risk perception was associated with ageing, higher frequency of cardiovascular risk factors and disease, and a poorer self-rated health status. The findings of this study highlight the low perception of cardiovascular risk in Italian women and suggest an urgent need to enhance knowledge and perception of CVD risk in women as a real health problem and not just as a as a life-threatening threat.

Why Do High-Risk Patients Develop or Not Develop Coronary Artery Disease? Metabolic Insights from the CAPIRE Study.

Traditional cardiovascular (CV) risk factors (RFs) and coronary artery disease (CAD) do not always show a direct correlation. We investigated the metabolic differences in a cohort of patients with a high CV risk profile who developed, or did not develop, among those enrolled in the Coronary Atherosclerosis in Outlier Subjects: Protective and Novel Individual Risk Factors Evaluation (CAPIRE) study. We studied 112 subjects with a high CV risk profile, subdividing them according to the presence (CAD/High-RFs) or absence of CAD (No-CAD/High-RFs), assessed by computed tomography angiography. The metabolic differences between the two groups were identified by gas chromatography-mass spectrometry. Characteristic patterns and specific metabolites emerged for each of the two phenotypic groups: high concentrations of pyruvic acid, pipecolic acid, p-cresol, 3-aminoisobutyric acid, isoleucine, glyceric acid, lactic acid, sucrose, phosphoric acid, trimethylamine-N-oxide, 3-hydroxy-3-methylglutaric acid, erythritol, 3-hydroxybutyric acid, glucose, leucine, and glutamic acid; and low concentrations of cholesterol, hypoxanthine, glycerol-3-P, and cysteine in the CAD/High-RFs group vs the No-CAD/High-RFs group. Our results show the existence of different metabolic profiles between patients who develop CAD and those who do not, despite comparable high CV risk profiles. A specific cluster of metabolites, rather than a single marker, appears to be able to identify novel predisposing or protective mechanisms towards CAD beyond classic CVRFs.