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Semaglutide, a glucagon-like peptide-1 receptor agonist, has emerged as a pivotal therapeutic agent in the management of the cardio-renal-metabolic continuum. Initially developed for glycemic control in type 2 diabetes mellitus, its benefits extend far beyond glucose regulation. Clinical trials have demonstrated semaglutide's potential to reduce major adverse cardiovascular events, particularly in overweight/obese patients with high cardiovascular risk, as well as improving functional capacity in patients suffering from heart failure with preserved left ventricular function. Additionally, it has shown promise in improving renal outcomes, such as slowing the progression of albuminuria and reducing the risk of chronic kidney disease in diabetic populations. These effects are likely due to its multifaceted mechanisms, including anti-inflammatory properties, weight reduction, blood pressure lowering, and direct renal protection. This review synthesizes current evidence on semaglutide's role in the interrelated domains of cardiovascular, renal, and metabolic health.

Immunotherapy has revolutionized the treatment of various cancers leading to a clear survival benefit with cured or long-surviving patients. Atherosclerosis and cancer share risk factors and molecular mechanisms and have as their common thread a state of chronic inflammation linked to a deregulation of the immune system. A growing body of evidence is accumulating on the potential worsening effect of immune checkpoint inhibitors on atherosclerosis, with subsequent worsening of patients' long-term cardiovascular risk. The molecular pathways implicated in the growth and deregulation of atherosclerotic plaques seem to be the same (CTLA-4, PD-1, PD-L1) as those on which the anti-tumor effect is exerted. Owing to the increasing number of cancer patients treated with immunotherapy and the improved survival with the possibility of prolonged disease control, it is necessary to know the potential increase in cardiovascular risk for atherosclerosis-related events and to establish all prevention measures to reduce it.

Infective endocarditis (IE) is an infective process involving the endocardium and, more frequently, the native heart valves, valvular prostheses and cardiac implantable electronic devices. IE can manifest with various non-specific symptoms making the diagnosis challenging. This condition is associated with high in-hospital and long-term mortality. Therefore, it is particularly important to prevent it by implementing an adequate antibiotic prophylaxis especially in patients at high risk undergoing invasive procedures. Moreover, it is pivotal to promptly diagnose IE, detect the presence of local and systemic complications, establish appropriate antibiotic therapy and identify the indication and timing for surgical treatment. In this focused review, we will provide answers to the most common questions regarding the epidemiology, causes, prophylaxis, diagnosis and antibiotic and surgical treatment of IE.

Due to the growing evidence of clinical benefits conferred by the reduction of low-density lipoprotein cholesterol (LDL-C) levels, the availability of multiple effective lipid-lowering agents, and guideline recommendations, clinicians not infrequently have to manage patients with low or very low LDL-C levels. In clinical practice it is essential to consider that, when LDL-C plasma concentrations are low, the Friedewald formula commonly used for LDL-C level calculation is less accurate, hence risk assessment should be integrated by using different methods for LDL-C level quantification and other parameters, such as non-high-density lipoprotein cholesterol and, where possible, apolipoprotein B, should be measured. As regards the clinical impact of low LDL-C levels, genetically determined hypocholesterolemia forms provide reassuring data on the effects of this condition in the long term, except for the forms with extremely low or undetectable LDL-C levels. Evidence from clinical studies that used highly effective lipid-lowering drugs, such as proprotein convertase subtilisin/kexin type 9 inhibitors, goes in the same direction. In these studies, the incidence of non-cardiovascular adverse events in patients who reached very low LDL-C levels was similar to that in the placebo arm. Overall, the fear of adverse effects should not deter intensive lipid-lowering treatment when indicated to reduce the risk of cardiovascular events.

The consumption of energy drinks (ED) has become a growing public health issue, since potentially ED-related serious adverse cardiovascular events, including arrhythmias, myocardial infarction, cardiomyopathies, and sudden cardiac death, have been reported in recent years. The substances contained in ED include caffeine, taurine, sugars, B group vitamins and phyto-derivatives, which, especially if taken in large quantities and in a short amount of time, could cause serious side effects through various mechanisms of action, such as increased blood pressure and QT interval prolongation. Although there are still many open questions on ED that require further specific investigations, there is an urgent need for information and educational plans to the population, as well as for regulatory actions, particularly regarding transparency of substances and possible adverse effects.

Background: Cancer is an important condition associated with the development of atrial fibrillation (AF). The objectives of the BLITZ-AF Cancer study were to collect real-life information on the clinical profile and use of antithrombotic drugs in patients with AF and cancer to improve clinical management, as well as the evaluation of the association between different antithrombotic treatments (or their absence) and the main clinical events., Methods: European multinational, multicenter, prospective, non-interventional study conducted in patients with AF (electrocardiographically confirmed) and cancer occurring within 3 years. The CHA2DS2-VASc and the HAS-BLED scores were calculated in all enrolled patients., Results: From June 2019 to July 2021, 1514 patients were enrolled, 36.5% women, from 112 cardiology departments in 6 European countries (Italy, Belgium, the Netherlands, Spain, Portugal and Ireland). Italy enrolled 971 patients in 77 centers. Average age of patients was 74 ± 9 years, of which 20.9% affected by heart failure, 18.1% by ischemic heart disease, 9.8% by peripheral arterial disease and 38.5% by valvular diseases; 41.5% of patients had a CHA2DS2-VASc score ≥4. The most represented cancer sites were lung (14.9%), colorectal tract (14.1%), prostate (8.8%), or non-Hodgkin's lymphoma (8.1%). Before enrollment, 16.6% of patients were not taking antithrombotic therapy, while 22.7% were on therapy with antiplatelet agents and/or low molecular weight heparin. After enrollment these percentages decreased to 7.7% and 16.6%, respectively and, at the same time, the percentage of patients on direct oral anticoagulant (DOAC) therapy increased from 48.4% to 68.4%, also to the detriment of those on vitamin K antagonist therapy., Conclusions: The BLITZ-AF Cancer study, which enrolled patients diagnosed with AF and cancer, highlights that the use of DOACs by cardiologists in this clinical context has increased, even though the guidelines on AF do not give accurate indications about oral anticoagulant therapy in patients with cancer.

The issue of suboptimal drug regimen adherence in secondary cardiovascular prevention presents a significant barrier to improving patient outcomes. To address this, the utilization of drug combinations, specifically single pill combinations (SPCs) and polypills, was proposed as a strategy to simplify treatment regimens. This approach aims to enhance treatment accessibility, affordability, and adherence, thereby reducing healthcare costs and improving patient health. The document is an ANMCO scientific statement on simplifying drug regimens for secondary cardiovascular prevention. It discusses the underuse of treatments despite available, effective, and accessible options, highlighting a significant gap in secondary prevention across different socioeconomic statuses and countries. The statement explores barriers to implementing evidence-based treatments, including patient, healthcare provider, and system-related challenges. The paper also reviews international guidelines, the role of SPCs and polypills in clinical practice, and their economic impact, advocating for their use in secondary prevention to improve patient outcomes and adherence.

Obesity is a chronic and relapsing disease due to the coexistence of a patient with predisposing individual characteristics and an obesogenic environment. The recent acquisition of detailed knowledge on the mechanisms underlying the energetic homeostasis paved the way to more effective therapeutic hypotheses as compared to traditional treatments. Since obesity is a complex issue, it requires a multidisciplinary approach which is difficult to implement. However, new drugs appear promising. Currently, therapeutic success is discrete in the short term, but unsatisfying in the long term due to the high probability of body weight gain. Cardiologists play a key role in managing patients with obesity, but they are not used to manage them. The aim of this document is to summarize knowledge that clinicians need to have to appropriately manage these patients. The paper emphasizes the pivotal role of an appropriate relationship with the patient to embark on a successful treatment journey. We analyze the criteria commonly used to diagnose obesity and point out strengths and limitations of different criteria. Furthermore, we discuss the figure of the obesitologist and the role of the cardiologist. In addition, we report the main components of an effective therapeutic strategy, from educational questions to pharmacological options.

Cardio-oncology rehabilitation (CORE) is not only an essential component of cancer rehabilitation, but also a pillar of preventive cardio-oncology. CORE is a comprehensive model based on a multitargeted approach and its efficacy has been widely documented; when compared to an "exercise only" program, comprehensive CORE demonstrates a better outcome. It involves nutritional counseling, psychological support and cardiovascular risk assessment, and it is directed to a very demanding population with a heavy burden of cardiovascular diseases driven by physical inactivity, cancer therapy-induced metabolic derangements and cancer therapy-related cardiovascular toxicities. Despite its usefulness, CORE is still underused in cancer patients and we are still at the dawning of remote models of rehabilitation (telerehabilitation). Not all cardio-oncology rehabilitation is created equal: a careful screening procedure to identify patients who will benefit the most from CORE and a multidisciplinary customized approach are mandatory to achieve a better outcome for cancer survivors throughout their cancer journey.The aim of this position paper is to provide an updated review of CORE not only for cardiologists dealing with this peculiar patient population, but also for oncologists, primary care providers, patients and caregivers. This multidisciplinary team should help cancer patients to maintain a healthy and active life before, during and after cancer treatment, in order to improve quality of life and to fight health inequities.

Scientific societies promote numerous activities, including the training of professionals. With the continuous growing of knowledge and the availability of new evidence in the cardiological field, the achievement and maintenance of knowledge and know-how is difficult. The evolving educational needs of professionals in cardiology have been analyzed during the 2023 ANMCO General States. Furthermore, the initiatives implemented to meet professionals' needs after the university medical training have been discussed. In this document, we report the main and most innovative training activities promoted by ANMCO, from distance training to simulation training, including courses for master's degree, training to and through clinical research and the potential role of teaching hospitals.

Atherosclerosis is a systemic disease that can involve different arterial districts. Traditionally, the focus of cardiologists has been on the diagnosis and treatment of atherosclerotic coronary artery disease (CAD). However, atherosclerosis localization in other districts is increasingly common and is associated with an increased risk of CAD and, more generally, of adverse cardiovascular events. Although the term peripheral arterial disease (PAD) commonly refers to the localization of atherosclerotic disease in the arterial districts of the lower limbs, in this document, in accordance with the European Society of Cardiology guidelines, the term PAD will be used for all the locations of atherosclerotic disease excluding coronary and aortic ones. The aim of this review is to report updated data on PAD epidemiology, with particular attention to the prevalence and its prognostic impact on patients with CAD. Furthermore, the key points for an appropriate diagnostic framework and a correct pharmacological therapeutic approach are summarized, while surgical/interventional treatment goes beyond the scope of this review.

Pulmonary hypertension (PH) is a frequent pathological condition worldwide, mainly secondary to cardiovascular and respiratory diseases, with a poor prognosis. Pulmonary arterial hypertension (PAH) is a rare form that affects the arterial pulmonary vasculature. PH and PAH are characterized by non-specific symptoms and a progressive increase of pulmonary vascular resistance that results in progressive, sometimes irreversible, right ventricular dysfunction. In recent years, a growing medical and social commitment on this disease allowed more accurate diagnosis in shorter times. However, the gap between guidelines and clinical practice remains a challenge for all medical doctors involved in the disease management. Considering the needs to share and describe diagnostic and therapeutic pathways, to measure the results obtained and to address the economical and organizational problems of this disease, all involved figures should collaborate to improve its prognostic impact and health expenses. In this consensus document, the PH experts of the Italian Association of Hospital Cardiologists (ANMCO) together with those of the Italian Society of Cardiology (SIC), address 1) definition, classification and unmet needs of PH and PAH; 2) classification and characteristics of centers involved in the diagnosis and treatment of the disease; 3) proposal of organization of a diagnostic-therapeutic pathway, based on robust and recent scientific evidence.

Technological innovation provides easily accessible tools capable of simplifying healthcare processes. Notably, digital technology application in the cardiology field can improve prognosis, reduce costs, and lead to an overall improvement in healthcare. The digitization of health data, with the use of electronic health records and of electronic health files in Italy, represents one of the fields of application of digital technologies in medicine. The 2023 States General of the Italian Association of Hospital Cardiologists (ANMCO) provided an opportunity to focus attention on the potential benefits and critical issues associated with the implementation of the aforementioned digital tools, artificial intelligence, and telecardiology. This document summarizes key aspects that emerged during the event.

For over 40 years, clinical research has been one of the most important aims of the Italian Association of Hospital Cardiologists (ANMCO), being an essential tool in pursuing promotion and fulfillment of good clinical practices in prevention, treatment and rehabilitation of cardiovascular diseases. Since 1992, with the creation of the Research Center (now part of the Heart Care Foundation), ANMCO is capable of independently and professionally managing all the aspects related to planning, management, and publication of the results of clinical studies. The other strength of ANMCO is the network built in Cardiology Departments on the whole territory of Italy, a human capital that allows ANMCO to deal with the new scientific challenges, in a context of profound changes in the social, economic, technological, and methodological setting. This document is based on the debate about the state of clinical research in Italy and the role of ANMCO in this setting that took place during the 2023 ANMCO States General.

Over the latest years, a worrying progressive reduction of medical specialists has been observed in Italy and in other European and non-European countries. This trend is assuming alarming proportions, especially considering the continuous population aging and the concomitant increase in the prevalence of chronic cardiovascular disease. The underlying reasons are complex and multifactorial. The purpose of this document, derived from the collegial discussion held during the 2023 ANMCO States General is to highlight the current critical issues regarding the lack of healthcare personnel in the cardiology field, examining the current and future Italian situation and proposing some potential strategies to counteract this alarming phenomenon.

It is well established that gender strongly influences cardiovascular risk factors, playing a crucial role in cardiovascular prevention, clinical pathways, diagnostic approach and treatment. Beyond the sex, which is a biological factor, gender entails a socio-cultural condition that impacts access and quality of care due to structural and institutional barriers. However, despite its great importance, this issue has not been adequately covered. Indeed sex and gender differences scarcely impact the clinical approach, creating a lot of disparities in care and outcomes of patients. Therefore, it becomes essential to increase the awareness of the importance of sex and gender influences on cardiovascular diseases. Moreover, new strategies for reducing disparities should be developed. Importantly, these differences should be taken into account in guideline recommendations. In this regard, it is crucial to include a greater number of women in clinical trials, since they are currently underrepresented. Furthermore, more women should be involved as member of international boards in order to develop recommendations and guidelines with more attention to this important topic.The aim of this ANMCO position paper is to shed light on gender differences concerning many cardiovascular drugs in order to encourage a more personalized therapeutic approach.

Over the last two decades, cardiovascular diseases have become the leading cause of chronic disease morbidity and mortality in Italy. Therefore, the chronic cardiovascular care landscape has evolved rapidly in an era of unprecedented demand. Furthermore, the COVID-19 pandemic has highlighted significant deficiencies in existing health and social care systems, especially in the management of chronic cardiovascular disease. In this scenario, the National Reform for Recovery and Resilience (PNRR) may represent a unique opportunity for the development of a new integrated care system between hospital and community. The Italian Association of Hospital Cardiologists (ANMCO) recognizes the need for a statement on the integrated cardiological community care to guide health professionals caring for people with chronic cardiovascular conditions. The aim of the present statement is to outline the evidence for a modern integrated cardiological community care identifying challenges and offering advice for a future transdisciplinary and multi-organizational approach to ensure best practice in the management of chronic cardiovascular disease.

Lipoprotein(a) [Lp(a)] is a well-established cardiovascular risk factor, whose relationship with atherosclerotic disease has been confirmed by epidemiological, genome-wide association, Mendelian randomization, and meta-analysis studies. This association is determined by its pro-atherogenic, pro-thrombotic and pro-inflammatory properties. Lp(a) is the most common monogenic risk factor for atherosclerosis, with a prevalence of about 1 in 5 people. Recently, its etiopathogenetic relationship with calcific and degenerative valvular heart diseases, particularly with aortic and mitral stenosis, has been suspected. It has not yet been demonstrated whether its reduction translates into a lower risk of cardiovascular events. Up to now, Lp(a) has been considered a non-modifiable risk factor, as current lipid-lowering drugs have limited effects on its levels. New specific lipid-lowering therapies with high efficacy in reducing circulating Lp(a) levels are being investigated in randomized trials; however, the effects of this reduction on cardiovascular outcomes are still being studied.

In recent decades, an incredible evolution in antithrombotic therapies for the treatment of patients suffering from atherosclerosis, atrial fibrillation and venous thromboembolism occurred, leading to the availability of increasingly safe drugs. However, bleeding complications associated with these drugs still have an important health, social and economic impact. Recently, with the aim of improving the acute management of patients with or at risk of major bleeding events, specific reversal agents of antithrombotic drugs have been developed. Although these agents have demonstrated their effectiveness in small pharmacodynamic studies or clinical trials, it is important to consider that the benefit of reversal of an antiplatelet or anticoagulant drug must always be counterbalanced by the possible prothrombotic effect caused by the removal of antithrombotic protection as well as by prothrombotic mechanisms related to bleeding, major surgery or trauma.In this ANMCO/SIMEU consensus document we summarize the main characteristics and efficacy studies of the currently available reversal agents and present practical flow-charts in which we suggest their possible use in patients with active bleeding or at high risk of major bleeding events.

The advent of direct oral anticoagulants (DOACs) has revolutionized the approach to thromboembolism prevention and treatment. The analysis of the evolution of the use of DOACs over the last decade has highlighted an overtaking in the DOAC use compared to vitamin K antagonists, with greater overall adherence to anticoagulant treatment and a reduction in ischemic events associated with atrial fibrillation. In clinical practice, particular attention should be paid to the use of the appropriate dosage based on the clinical characteristics of the individual patient, in order to avoid over- or under-treatment with a consequent increase in adverse event risk. In general, the four currently available DOACs have different pharmacokinetic and pharmacodynamic characteristics that should be taken into consideration when choosing the drug and its dosage. This review summarizes differences and similarities of DOACs in complex clinical scenarios such as elderly patients, patients with chronic kidney disease, cancer patients, and multi-treated patients.

In the last decades, because of the improvements in the percutaneous treatment of coronary heart disease, valvular heart disease, congenital heart defects, and the increasing number of cardiac resynchronization therapy and cardioverter-defibrillator implantations, the interventional cardiologists' radio-exposure has importantly risen, causing concerns for ionizing radiation-associated diseases such as cancer and neurodegenerative disorders. Consequently, the radiation exposure issue importantly affects operators' safety. However, our knowledge of this field is poor and most operators are unaware to be at risk, especially because of the absence of effective preventive measures. The aim of this ANMCO position paper is to improve the awareness of operators and identify new ways of reducing operator ionizing radiation dose and minimizing the risk.

The management of the patient with fever in the intensive cardiac care unit begins with a thorough evaluation of the patient, particularly symptoms, clinical history and physical examination, to provide information regarding the origin of the fever. The global evaluation of the patient should be integrated with blood and microbiological tests, in particular blood culture and swab. The laboratory, microbiologic or radiologic tests could be more or less detailed and targeted depending on the type of suspected infection and clinical conditions of the patient. When therapy is necessary, it is crucial to switch, as soon as possible, from broad spectrum antibiotic therapy to antibiotic therapy based on the results of the microbiological exams. Antibiotic therapy could be associated with antipyretic and specific organ support therapy when necessary.

Electrical storm (ES) is characterized by at least three separate episodes of ventricular arrhythmia (VA) over 24 h that require treatment or an incessant VA lasting >12 h. The incidence is higher in patients with implantable cardioverter-defibrillators (ICDs) in secondary prevention and the main manifestation is monomorphic VA. ES onset represents a major event in the history of patients with cardiomyopathies that significantly worsens prognosis. The management of ES is complex and requires a multidisciplinary approach including a comprehensive clinical assessment, resuscitation and sedation management skills, ICD reprogramming, ablation, and neuromodulation procedures. ES early recognition and prompt treatment initiation increase the chances of therapeutic success. Each one of these aspects will be properly discussed in the present decalogue. Notably, ES management remains a challenge, with only limited available evidence from small retrospective series and a substantial lack/limited number of randomized or prospective trials. The spectrum of available antiarrhythmic drugs is limited, as well as their efficacy. The future hope is that larger prospective studies will be able to answer important questions, concerning the most effective pharmacologic strategies, the timing for the invasive treatment, the indications for acute neuromodulation strategies and for the circulatory support tools.

Nowadays, a progressive and exponential increase in the use of invasive and non-invasive instrumental diagnostics and therapeutic services has been shown. Although unnecessary, instrumental examinations are often largely prescribed, replacing clinical evaluation. Their correct use, on the contrary, would address precise epidemiological and clinical contexts. Therefore identifying whether a test or procedure is appropriate or not plays a crucial role in clinical practice. Several documents from scientific societies and expert groups indicate the most appropriate cardiovascular diagnostic and therapeutic procedures. The international Choosing Wisely campaign invited the main scientific societies to identify five techniques or treatments used in their field that are often unnecessary and may potentially damage patients. The Italian Association of Hospital Cardiologists (ANMCO) joined the project identifying the five cardiological practices in our country at greater risk of inappropriateness in 2014. This list has recently been updated. Moreover, possible solutions to this problem have been proposed.

With the growing knowledge about the role of inflammatory processes in the pathogenesis of atherosclerotic lesions, inflammation has been identified as a cardiovascular risk factor and therapeutic target to reduce the residual risk in patients with atherosclerotic disease. Several therapeutic agents with anti-inflammatory action have been tested to evaluate their efficacy and safety in the context of atherosclerotic cardiovascular diseases. Among these, colchicine, a drug with multiple therapeutic effects including anti-inflammatory action, in randomized clinical trials conducted in the setting of atherosclerotic cardiovascular disease secondary prevention, significantly reduced the risk of adverse cardiovascular events.This position paper of the Italian Association of Hospital Cardiologists (ANMCO) summarizes the main biological mechanisms through which colchicine contributes to the inhibition of inflammatory processes that increase the atherosclerotic cardiovascular risk. Furthermore, the document reports the available evidence on clinical impact of colchicine treatment in the reduction of residual cardiovascular risk in chronic and acute coronary syndromes. Finally, practical information is provided regarding the use of this drug in this specific clinical setting, emphasizing precautions and possible side effects.

Modern coronary diagnostic methods, including cardiac computed tomography and intracoronary imaging, allow the identification of vulnerable coronary plaques with a high probability of complicating and causing acute coronary syndrome. The treatment limited to the plaques responsible for ischemic events could not be enough to prevent major cardiovascular events because most flow-limiting plaques are quiescent or slowly evolving. In several cases the plaques responsible for acute event determine a moderate reduction of the vessel lumen but have well-defined characteristics of vulnerability. The purpose of this review is (i) to describe the characteristics of these plaques based on both the pathological anatomy and computed tomography and intracoronary imaging findings and the associated clinical risk of developing future coronary events; (ii) to evaluate available trials on early treatment of vulnerable plaques by percutaneous revascularization; and (iii) to propose a decision-making algorithm in primary prevention integrating the search for myocardial ischemia and vulnerable plaques.

Over the last decade, pharmacological therapies for primary and secondary prevention of chronic coronary syndromes enriched with new agents have been demonstrated to be effective in reducing cardiovascular adverse events. However, currently available evidence on treatment for anginal symptom control is weaker. This position paper of the Italian Association of Hospital Cardiologists (ANMCO) aims to briefly report evidence that supports the use of anti-ischemic drugs for chronic coronary syndromes. Furthermore, we propose a therapeutic algorithm for the choice of the most appropriate drug on the basis of the clinical characteristics of the individual patient.

Acute respiratory failure is a frequent complication of patients admitted to the intensive cardiac care unit and it is associated with a poor short- and long-term outcome. Acute respiratory failure can be managed with traditional oxygen therapy, with high-flow nasal cannula, continuous positive airway pressure, non-invasive ventilation or invasive ventilation according to clinical and blood gas condition. The use of advanced respiratory therapies is associated with both respiratory and hemodynamic effects, therefore the intensivist cardiologist should know deeply these respiratory devices. The intensivist cardiologist should perform an early diagnosis of acute respiratory failure, an appropriate selection of the respiratory device, and accurate monitoring and management to obtain clinical improvement and to avoid mechanical invasive ventilation.

Research focused on lipid-lowering treatments has led to the development of new therapeutic options aimed at cardiovascular risk reduction. Gene silencing represents one of the most innovative approaches to reduce low-density lipoprotein cholesterol (LDL-C). Inclisiran is a small interfering RNA that inhibits proprotein convertase subtilisin/kexin type 9 synthesis and promotes LDL-C clearance by enhancing LDL-C receptor expression on hepatocyte cell surface. Several clinical studies have demonstrated inclisiran efficacy in terms of LDL-C reduction (~50%) with a dosage regimen of 300 mg administered twice a year after the first two doses administered at time 0 and after 90 days. Inclisiran use has recently been approved by the European and American drug regulatory agencies as a therapeutic option in addition to the maximum tolerated statin therapy in adults with primary hypercholesterolemia or mixed dyslipidemia who need further LDL-C reduction.

Progressive legalization for medical conditions or recreational use has led to an increased use of cannabis and synthetic cannabinoids over the past years. Most consumers are young and healthy, without cardiovascular risk factors; however, this population is expected to include older individuals. Thus, concerns have arisen about safety and short- and long-term potential adverse effects, with special emphasis on vulnerable groups. Studies show that cannabis might be linked with thrombosis, inflammation, and atherosclerosis, and many reports have associated cannabis and synthetic cannabinoids use with serious adverse cardiovascular complications, including myocardial infarction, cardiomyopathy, arrhythmias, stroke, and cardiac arrest. A clearly defined causal role cannot be demonstrated, because of confounding variables. Physicians need to become aware of the possible spectrum of clinical presentations, not only for timely diagnosis and treatment, but also for effective counseling and prevention.In this review, we aim to provide a basic understanding of the physiological effects of cannabis, the role of the endocannabinoid system in cardiovascular disease, and the cardiovascular consequences of cannabis and synthetic cannabinoid use, including a comprehensive review of the studies and case reports that provide supportive evidence for cannabis as a trigger of adverse cardiovascular events according to the current literature.

Growing evidence supporting the central role of hypercholesterolemia in atherosclerotic disease pathogenesis and progression has led to the development of new therapeutic approaches. Bempedoic acid has recently been approved for marketing following several studies that demonstrated its efficacy and safety. This drug represents a new therapeutic option that, like statins, acts on the enzymatic cascade that is involved in cholesterol synthesis. However, its hepatic selectivity of action reduces the risk of muscle adverse effects. This ANMCO document highlights clinical settings in which bempedoic acid represents a particularly useful therapeutic option. Furthermore, the document discusses the possibilities of use based on both international recommendations and current national regulations. Finally, we report practical guidance on hypercholesterolemia management in light of the available therapeutic armamentarium.

Pathophysiologic processes promoted by uric acid, including inflammation and oxidative stress, play a key role in the pathogenesis of several cardiovascular diseases. Furthermore, a number of epidemiological studies have shown an association between uric acid plasma levels and multiple cardiovascular risk factors. This ANMCO statement provides an update on available evidence regarding the association between elevated plasma uric acid levels and cardiovascular disease risk and the safety and efficacy of uric acid lowering agents (allopurinol and febuxostat) used in patients with urate crystal deposits. In addition, it summarizes practical indications for the use of these drugs in at-risk patients or in patients with cardiovascular disease.

Extended risk stratification and optimal management of patients with a permanently increased risk of sudden cardiac death (SCD) is becoming increasingly important. There are several clinical conditions where the risk of arrhythmic death is present albeit only transient. As an example, patients with depressed left ventricular function have a high risk of SCD that may be only transient when there is a significant recovery of function. It is important to protect the patients while receiving the recommended measures and drugs that may either lead or not to an improved left ventricular function. In several other conditions a transient risk of SCD can be observed even if the left ventricular function is not compromised. Examples are patients with acute myocarditis, during the diagnostic work-up of some arrhythmic conditions or after extraction of infected catheters while eradicating the associated infection. In all these conditions it is important to offer a protection to these patients. The wearable cardioverter-defibrillator (WCD) is of particular importance as a temporary non-invasive technology for both arrhythmia monitoring and therapy in patients with increased risk of SCD. Previous studies have shown the WCD to be an effective and safe therapy for the prevention of SCD caused by ventricular tachycardia/fibrillation. The aim of this ANMCO position paper is to provide a recommendation for clinical utilization of the WCD in Italy, based upon current data and international guidelines. In this document we will review the WCD functionality, indications, clinical evidence as well as guideline recommendations. Finally, a recommendation for the utilization of the WCD in routine clinical practice will be presented, in order to provide physicians with a practical guidance for SCD risk stratification in patients who may benefit from this device.

In the growing therapeutic armamentarium for heart failure management, vericiguat represents an innovative therapeutic option. The biological target of this drug is different from that of other drugs for heart failure. Indeed, vericiguat does not inhibit neurohormonal systems overactivated in heart failure or sodium-glucose cotransporter 2 but stimulates the biological pathway of nitric oxide and cyclic guanosine monophosphate, which is impaired in patients with heart failure. Vericiguat has recently been approved by international and national regulatory authorities for the treatment of patients with heart failure and reduced ejection fraction who are symptomatic despite optimal medical therapy and have worsening heart failure. This ANMCO position paper summarizes key aspects of vericiguat mechanism of action and provides a review of available clinical evidence. Furthermore, this document reports use indications based on international guideline recommendations and local regulatory authority approval at the time of writing.

Patients with pulmonary embolism are a heterogeneous population and, after the acute phase and the first 3-6 months, the main issue is whether to continue, and hence how long and at what dose, or to stop anticoagulation therapy. In patients with venous thromboembolism (VTE), direct oral anticoagulants (DOACs) are the recommended treatment (class I, level of evidence B in the latest European guidelines), and in most cases, an "extended" or "long-term" low-dose therapy is warranted. This paper aims to provide a practical management tool to the clinician dealing with pulmonary embolism follow-up: from the evidence behind the most used exams (D-dimer, ultrasound Doppler of the lower limbs, imaging tests, recurrence and bleeding risk scores), and the use of DOACs in the extended phase, to six real clinical scenarios with the relative management in the acute phase and at follow-up. Lastly, a practical algorithm is shown to deal with anticoagulation therapy in the follow-up of VTE patients in a simple, schematic, and pragmatic way.

Patients with type 2 diabetes mellitus are at an increased risk of cardiovascular disease and microvascular and macrovascular complications. Although multiple classes of antidiabetic drugs are currently available, cardiovascular complications of diabetes still cause considerable morbidity and premature cardiovascular mortality in diabetic patients. The development of new drugs represented a conceptual breakthrough in the treatment of patients with type 2 diabetes mellitus. In addition to improving glycemic homeostasis, these new treatments have consistently demonstrated relevant cardiovascular and renal benefits due to their multiple pleiotropic effects. The aim of this review is to analyze the direct and indirect mechanisms by which glucagon-like peptide 1 receptor agonists favorably impact cardiovascular outcome and report current indications for their implementation in clinical practice based on national and international guidelines.

Degenerative calcific aortic valve stenosis (CAVS) is a chronic disease whose prevalence has increased over the last decade because of the aging of the general population. CAVS pathogenesis is characterized by complex molecular and cellular mechanisms that promote valve fibro-calcific remodeling. During the first phase, referred to as initiation, the valve undergoes collagen deposition and lipid and immune cell infiltration due to mechanical stress. Subsequently, during the progression phase, the aortic valve undergoes chronic remodeling through osteogenic and myofibroblastic differentiation of interstitial cells and matrix calcification. Knowledge of the mechanisms underlying CAVS development supports the resort to potential therapeutic strategies that interfere with fibro-calcific progression. Currently, no medical therapy has demonstrated the ability to significantly prevent CAVS development or slow its progression. The only treatment available in symptomatic severe stenosis is surgical or percutaneous aortic valve replacement. The aim of this review is to highlight the pathophysiological mechanisms involved in CAVS pathogenesis and progression and to discuss potential pharmacological treatments able to inhibit the main pathophysiological mechanisms of CAVS, including lipid-lowering treatment with lipoprotein(a) as emergent therapeutic target.

The kidney plays an important role in maintaining glucose homeostasis which is used as a metabolic substrate, generated through the mechanism of gluconeogenesis and reabsorbed in the glomerular filtrate through the action of sodium-glucose cotransporters 1 and 2 (SGLT1/2) located in the proximal tubule. Recent studies have shown that inhibition of renal glucose reabsorption, achieved through the administration of sodium-glucose cotransporter inhibitors, significantly reduces renal adverse events and exacerbations of heart failure, not only in diabetic patients, with and without confirmed cardiovascular damage, but also in patients with advanced chronic renal failure and in patients with heart failure with reduced ejection fraction regardless of the presence of diabetes. The extent of the benefit was relevant in the various clinical conditions studied, and led to a significant reduction in the major adverse cardiovascular outcomes recorded in each study. In all controlled studies, the efficacy of sodium-glucose cotransporter inhibitors was strongly associated with the reduction in progression of renal damage, as evidenced by the significant reduction in overall mortality obtained in the two studies that enrolled populations of diabetic and non-diabetic patients with advanced chronic renal failure. Both studies were stopped early at the interim analysis due to the evident superiority of the therapy in the treated arm.The purpose of this review is to examine the role of SGLT2/1 both in physiological conditions that in the course of cardio-nephropathy associated or not with type 2 diabetes mellitus and the effect of SGLT2/1 inhibition on clinical outcomes in different cardiovascular risk population enrolled in different randomized controlled clinical trials.

Patients suffering from acute coronary syndromes (ACS) present a high risk of recurrence and new adverse cardiovascular events after hospital discharge. Elevated plasma LDL-cholesterol (LDL-C) levels have been shown to be a causal factor for the development of coronary heart disease, and robust clinical evidence has documented that a decrease of LDL-C levels correlates linearly with a reduction in cardiovascular events. Recent studies have also demonstrated the safety and efficacy of an early and significant reduction in LDL-C levels in patients with ACS.In this position paper, ANMCO proposes a decision algorithm on early adoption of lipid-lowering strategies at hospital discharge and short-term follow-up of patients with ACS, in the light of the multiple evidence generated in recent years on the treatment of hypercholesterolemia and the available therapeutic options, considering current reimbursement criteria.

Cardiac amyloidosis, in the three forms of immunoglobulin light chain (AL), transthyretin (ATTR) wild type (ATTRwt) and mutated (ATTRv) amyloidosis, is an increasingly known and recognized disease in the cardiovascular setting. The first stage of the patient's journey is the clinical suspicion of the disease, which is placed, in presence of a hypertrophic phenotype, by the identification of red flags, both extracardiac and cardiac clues whose presence increase the probability of being faced with a patient with this disease. The second stage is represented by diagnosis, which occurs with certainty through the identification of amyloid substance in cardiac tissue. This stage is spotted in wo parts, i.e. disease confirmation and disease etiology definition (AL vs ATTRwt vs ATTRv). However, it is possible in some selected cases to make a diagnosis of ATTR without the need for tissue assessment, in presence of a positive grade 2-3 bisphosphonate scintigraphy and absence of monoclonal component. Once the diagnosis has been made, the third stage is the assessment of prognosis, the fourth is the patient therapy pathway and fifth is the follow-up plan. Prognosis evaluation is based on different staging systems at the onset of the disease, whose applicability in the era of new effective therapies is still to be defined. To date, the transthyretin tetramer stabilizer tafamidis is the only approved treatment for both wild-type and mutant ATTR cardiomyopathy without polyneuropathy, while ATTRv with associated neuropathy can benefit from treatment with patisiran, an inhibitor of hepatic protein synthesis. Therapies for complications and comorbidities, must be addressed individually, due to the lack of specific clinical trials on this category of patients. In fact, it is important to take into consideration the risks linked to the use of some drugs due to the infiltration of the conduction tissue by the amyloid substance, which increases the risk of bradycardia and heart blocks, the tendency towards hypotension and the increased thromboembolic risk. It is also essential to follow the course of the disease and the efficacy of the treatment in affected patients with a standardized follow-up, and to identify early the signs/symptoms of the disease in asymptomatic TTR mutation carriers.This ANMCO position paper on amyloidosis aims to provide the clinical cardiologist with a practical summary of the disease, to accompany the patient with amyloidosis in the various stages of his journey.

Circulatory shock is a clinical condition characterized by hypotension and organ hypoperfusion, potentially fatal if the underlying cause is not promptly identified and corrected. Circulatory shock outcome is certainly conditioned from early diagnosis and early and adequate therapy. The aim of this review is to provide a tool for a rapid differential diagnosis among the various phenotypes of circulatory shock, based on the clinical, hemodynamic and biochemical profile. We also prompt to emphasize the role of multiparametric monitoring from the early phases of the management and the need to implement the time-dependent network to improve the outcome of these critical patients.

Atrial fibrillation (AF) accounts for 2% of the total presentations to the emergency department (ED) and represents the most frequent arrhythmic cause for hospitalization. It steadily increases the risk of thromboembolic events and is often associated with several comorbidities that negatively affect patient's quality of life and prognosis. AF has a considerable on healthcare resources, making the promotion of an adequate and coordinated management of this arrhythmia necessary in order to avoid clinical complications and to implement the adoption of appropriate technological and pharmacological treatment options. AF management varies across regions and hospitals and there is also heterogeneity in the use of anticoagulation and electric cardioversion, with limited use of direct oral anticoagulants. The ED represents the first access point for early management of patients with AF. The appropriate management of this arrhythmia in the acute setting has a great impact on improving patient's quality of life and outcomes as well as on rationalization of the financial resources related to the clinical course of AF. Therefore, physicians should provide a well-structured clinical and diagnostic pathway for patients with AF who are admitted to the ED. This should be based on a tight and propositional collaboration among several specialists, i.e. the ED physician, cardiologist, internal medicine physician, anesthesiologist. The aim of this ANMCO-SIMEU consensus document is to provide shared recommendations for promoting an integrated, accurate, and up-to-date management of patients with AF admitted to the ED or Cardiology Department, so as to make it homogeneous across the national territory.

Gut microbiota impacts host health by mediating beneficial physiological processes. However, growing evidence supports the potential role of microbiota in disease development and progression. In this review, we report current knowledge on pathophysiologic processes mediated by gut microbiota that may be implicated in atherosclerosis development and progression. We also summarize findings provided by clinical studies that indicate an association between gut microbiota composition and/or function and atherosclerotic cardiovascular diseases. Finally, we discuss potential strategies to impact gut microbiota composition and/or function in order to reduce the atherosclerotic cardiovascular risk.

Sodium-glucose cotransporter 2 inhibitors (SGLT2-i), initially developed as glucose-lowering agents for the treatment of type 2 diabetes, based on significant clinical benefits shown in patients with heart failure, have recently been included among the first-line drugs for the treatment of heart failure with reduced ejection fraction. International guidelines recommend SGLT2-i use in association with neuro-hormonal modulators (renin-angiotensin blockers, beta-blockers, and aldosterone antagonists). Although SGLT2-i are well tolerated, for an appropriate use and to maximize clinical benefits, it is important to know potential side effects and conditions that may lead to an increased risk of adverse events. The aim of this ANMCO document is to briefly report clinical evidence that support SGLT2-i use in patients with heart failure and provide practical indications for clinical implementation.

In patients with atherosclerotic disease, the occurrence of atherothrombotic events is the main determinant of morbidity and mortality. Growing evidence suggests the involvement of the coagulation pathway in the atherosclerotic process and the benefit of antithrombotic agents, such as direct oral anticoagulants, which interfere with both platelet aggregation and the coagulation cascade. The COMPASS trial has shown that in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD), low-dose rivaroxaban (2.5 mg twice daily) added to acetylsalicylic acid (ASA) 100 mg reduces major vascular events and mortality, with an increase in major bleeding but not in fatal bleeding or involving a critical organ. The reduction in major cardiovascular events has been confirmed in the overall population with CAD and in both patients with and without a previous percutaneous coronary revascularization, and also in patients with previous coronary bypass surgery. In patients with PAD, the combination of rivaroxaban 2.5 mg twice daily and ASA was found to reduce both major adverse cardiovascular events and major adverse limb events, including major limb amputations. In clinical practice, the use of rivaroxaban 2.5 mg co-administered with ASA has been approved in both patients with CAD and symptomatic PAD at high risk of ischemic events. However, in Italy, the national health system reimbursement is provided only for patients with PAD. In patients treated with rivaroxaban 2.5 mg, assessment and monitoring of bleeding risk is crucial to achieve the maximum clinical benefit.

Heart failure with improved ejection fraction (HFimpEF) represents a nosological entity that has recently been recognized and has little evidence from the literature. Available data indicate an increasing incidence of this patient group, consistent with the progressive improvement and implementation of medical therapy of heart failure with reduced ejection fraction (HFrEF). Furthermore, it is important to underline that the therapy itself should not be suspended after ejection fraction recovery, to avoid the recurrence of worse systolic dysfunction and patient outcomes. Only recently a randomized clinical study has been published, which enrolled also this patient subgroup, the DELIVER trial. Other data will soon become available, given the interest of the scientific community for this subgroup of patients, whose best management remains controversial. Since many studies suggest that the probability of myocardial recovery in HFrEF patients might be as high as 40%, depending on the case series taken into account, whereas the time to recovery might even be 12 months, the appropriate timing of device implantation, such as the defibrillator, in this setting deserves careful consideration.

Geriatric patients are an increasing population and cancer treatment in this population is a challenging and unsolved issue. Ageing is characterized by low-grade inflammation (inflamm-ageing), an important driver for age-related diseases such as cardiovascular diseases and cancer. These chronic conditions share pathophysiological bases, risk factors and may coexist. The burden of comorbidities lowers the threshold for cardiotoxic effects of oncologic treatments. Geriatric assessment is helpful in identifying the peculiar vulnerabilities of this complex population, but a multidisciplinary approach (with oncologists and cardio-oncologists) is needed to improve the appropriateness of care. In this ANMCO position paper, we define the role of cardio-oncologists in the different scenarios of older cancer patients (active cancer, long-term survivors), the importance of geriatric assessment, the unmet needs of survivors and the complexity of comorbidity management.