[Dual pathway inhibition in peripheral arterial disease]. / "Dual pathway inhibition" nell'arteriopatia periferica.

Despite its high worldwide prevalence and the intuitable negative prognostic connotation, for a long time peripheral artery disease (PAD) has not been the subject of particular interest by the cardiac scientific community. The availability of a new therapeutic strategy (low-dose rivaroxaban associated with acetylsalicylic acid) has reignited interest in PAD. The clear evidence derived from the COMPASS and VOYAGER PAD trials, with the possibility of using dual pathway inhibition, has given new energy to the therapeutic front against symptomatic PAD also associated with coronary artery disease. This review article aims to revisit the pathophysiological concepts underlying PAD and the path of the various clinical trials that have led to new scientific evidence.

[Polygenic risk score: a new approach to cardiovascular prevention?] / Score di rischio poligenico: un nuovo approccio alla prevenzione cardiovascolare?

Long-lasting epidemiological studies showed that prevention of coronary artery disease (CAD) is highly feasible with the management of several conditions called "risk factors", such as hypertension, cholesterol, smoking, etc. Nevertheless, risk stratification for primary prevention using a statistical combination of risk factors is suboptimal, as conventional risk factors are age-dependent, so that their treatment would be too late to be effective. Genetic risk stratification, built on the genetic variants linked to CAD, has the advantage of being embedded in DNA and then it is independent of age. The rapid advancement of DNA analysis techniques has made it possible to identify many variants and to produce easily a statistical combination of them to obtain a polygenic risk score (PRS). Prospective clinical trials based on risk stratification for CAD using the PRS have shown that statin therapy is associated with a higher reduction in cardiac events in the high genetic risk group compared with the low genetic risk group. A wide clinical use of the PRS, however, is presently not possible, basically due to the lack of a standard in production and validation of the PRS, but genetic risk stratification has the potential to revolutionize primary prevention.

Antibiotic Prophylaxis and Treatment for Cardiac Device Infections.

Cardiac device infections (CDIs) are a serious complication in patients with implanted devices, resulting in increased morbidity, prolonged hospital stay, and increased healthcare costs. The effective management of these infections involves a combination of appropriate antibiotic therapy and preventive strategies aimed at reducing the risk of infection. The role of antibiotic prophylaxis in infection prevention is crucial, including the emerging use of antibiotic-supported tools and other local antibiotic delivery systems, which may reduce the risk of infection at the device implant site. In this contemporary review, we provide an overview of the prophylactic treatment and different antibiotic regimens for the treatment of CDIs, emphasizing early diagnosis, appropriate choice of antibiotics, and individualized treatment.

[Atherosclerosis, cancer and immune checkpoint inhibitors]. / Aterosclerosi, cancro e inibitori dei checkpoint immunitari.

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.

[Low and very low cholesterol levels: what we need to know]. / Livelli di colesterolo bassi e molto bassi: cosa è necessario sapere.

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.

[Air pollution and cardiovascular disease]. / Inquinamento dell'aria e malattie cardiovascolari.

Although there is substantial evidence on the harmful effects of air pollution on human health, these are scarcely considered in the general clinical practice and also in the context of cardiovascular disease prevention. In light of the numerous epidemiological and basic research studies that have demonstrated the unfavorable impact of air pollution on the cardiovascular system, this review aims to bring this aspect to the attention of clinicians. This work describes the main air polluting components that can contribute to the onset and progression of cardiovascular diseases. The pathophysiological mechanisms underlying the impact of pollutants on the cardiovascular system and the available evidence regarding their effect on cardiovascular risk factors are reported. This article also examines the evidence relating to the correlation between environmental pollutants and some specific cardiovascular diseases, including acute coronary syndromes, cerebrovascular diseases, heart failure, and arrhythmias. Finally, the possible strategies to be implemented to limit pollution-induced cardiovascular damage are analyzed.

Aspirin in Primary Prevention: Looking for Those Who Enjoy It.

Based on a wealth of evidence, aspirin is one of the cornerstones of secondary prevention of cardiovascular disease. However, despite several studies showing efficacy also in primary prevention, an unopposed excess risk of bleeding leading to a very thin safety margin is evident in subjects without a clear acute cardiovascular event. Overall, the variability in recommendations from different scientific societies for aspirin use in primary prevention is a classic example of failure of simple risk stratification models based on competing risks (atherothrombosis vs. bleeding), perceived to be opposed but intertwined at the pathophysiological level. Notably, cardiovascular risk is dynamic in nature and cannot be accurately captured by scores, which do not always consider risk enhancers. Furthermore, the widespread use of other potent medications in primary prevention, such as lipid-lowering and anti-hypertensive drugs, might be reducing the benefit of aspirin in recent trials. Some authors, drawing from specific pathophysiological data, have suggested that specific subgroups might benefit more from aspirin. This includes patients with diabetes and those with obesity; sex-based differences are considered as well. Moreover, molecular analysis of platelet reactivity has been proposed. A beneficial effect of aspirin has also been demonstrated for the prevention of cancer, especially colorectal. This review explores evidence and controversies concerning the use of aspirin in primary prevention, considering new perspectives in order to provide a comprehensive individualized approach.

Inotropic Agents: Are We Still in the Middle of Nowhere?

Inotropes are prescribed to enhance myocardial contractility while vasopressors serve to improve vascular tone. Although these medications remain a life-saving therapy in cardiovascular clinical scenarios with hemodynamic impairment, the paucity of evidence on these drugs makes the choice of the most appropriate vasoactive agent challenging. As such, deep knowledge of their pharmacological and hemodynamic effects becomes crucial to optimizing hemodynamic profile while reducing the potential adverse effects. Given this perspective, it is imperative for cardiologists to possess a comprehensive understanding of the underlying mechanisms governing these agents and to discern optimal strategies for their application across diverse clinical contexts. Thus, we briefly review these agents' pharmacological and hemodynamic properties and their reasonable clinical applications in cardiovascular settings. Critical interpretation of available data and the opportunities for future investigations are also highlighted.

Exploring the Perioperative Use of DOACs, off the Beaten Track.

A notable increase in direct oral anticoagulant (DOAC) use has been observed in the last decade. This trend has surpassed the prescription of vitamin K antagonists (VKAs) due to the absence of the need for regular laboratory monitoring and the more favorable characteristics in terms of efficacy and safety. However, it is very common that patients on DOACs need an interventional or surgical procedure, requiring a careful evaluation and a challenging approach. Therefore, perioperative anticoagulation management of patients on DOACs represents a growing concern for clinicians. Indeed, while several surgical interventions require temporary discontinuation of DOACs, other procedures that involve a lower risk of bleeding can be conducted, maintaining a minimal or uninterrupted DOAC strategy. Therefore, a comprehensive evaluation of patient characteristics, including age, susceptibility to stroke, previous bleeding complications, concurrent medications, renal and hepatic function, and other factors, in addition to surgical considerations, is mandatory to establish the optimal discontinuation and resumption timing of DOACs. A multidisciplinary approach is required for managing perioperative anticoagulation in order to establish how to face these circumstances. This narrative review aims to provide physicians with a practical guide for DOAC perioperative management, addressing the most controversial issues.

Coagulation Tests and Reversal Agents in Patients Treated with Oral Anticoagulants: The Challenging Scenarios of Life-Threatening Bleeding and Unplanned Invasive Procedures.

In clinical practice, the number of patients treated with direct oral anticoagulants (DOACs) has consistently increased over the years. Since anticoagulant therapy has been associated with an annual incidence of major bleeding (MB) events of approximately 2% to 3.5%, it is of paramount importance to understand how to manage anticoagulated patients with major or life-threatening bleeding. A considerable number of these patients' conditions necessitate hospitalization, and the administration of reversal agents may be imperative to manage and control bleeding episodes effectively. Importantly, effective strategies for reversing the anticoagulant effects of DOACs have been well recognized. Specifically, idarucizumab has obtained regulatory approval for the reversal of dabigatran, and andexanet alfa has recently been approved for reversing the effects of apixaban or rivaroxaban in patients experiencing life-threatening or uncontrolled bleeding events. Moreover, continuous endeavors are being made to develop supplementary reversal agents. In emergency scenarios where specific reversal agents might not be accessible, non-specific hemostatic agents such as prothrombin complex concentrate can be utilized to neutralize the anticoagulant effects of DOACs. However, it is paramount to emphasize that specific reversal agents, characterized by their efficacy and safety, should be the preferred choice when suitable. Moreover, it is worth noting that adherence to the guidelines for the reversal agents is poor, and there is a notable gap between international recommendations and actual clinical practices in this regard. This narrative review aims to provide physicians with a practical approach to managing specific reversal agents.

Prevention and Risk Assessment of Cardiac Device Infections in Clinical Practice.

The implantation of cardiac electronic devices (CIEDs), including pacemakers and defibrillators, has become increasingly prevalent in recent years and has been accompanied by a significant rise in cardiac device infections (CDIs), which pose a substantial clinical and economic burden. CDIs are associated with hospitalizations and prolonged antibiotic therapy and often necessitate device removal, leading to increased morbidity, mortality, and healthcare costs worldwide. Approximately 1-2% of CIED implants are associated with infections, making this a critical issue to address. In this contemporary review, we discuss the burden of CDIs with their risk factors, healthcare costs, prevention strategies, and clinical management.

Italian Association of Hospital Cardiologists position paper-obesity in adults: a clinical primer.

Obesity is a chronic and relapsing disease characterized by the interaction between individual predispositions and an obesogenic environment. Recent advances in understanding the mechanisms of energetic homoeostasis paved the way to more effective therapeutic approaches compared with traditional treatments. Since obesity is a complex disease, it necessitates a multi-disciplinary approach whose implementation remains challenging. Nonetheless, emerging pharmacological interventions appear promising. Currently, therapeutic success is discreet in the short term but often fails to maintain long-term weight loss due to a high likelihood of weight regain. Cardiologists play a key role in managing patients with obesity, yet often lack familiarity with its comprehensive management. The aim of this document is to summarize knowledge to consolidate essential knowledge for clinicians to effectively treat patients living with obesity. The paper emphasizes the pivotal role of a strong patient-clinician relationship in navigating successful treatment. We analyse the criteria commonly used to diagnose obesity and point out the strengths and limitations of different criteria. Furthermore, we discuss the role of obesiologists and the contributions of cardiologists. In addition, we detail key components of effective therapeutic strategies, including educational aspects and pharmacological options.

Italian Association of Hospital Cardiologists Position Paper 'Gender discrepancy: time to implement gender-based clinical management'.

It has been well assessed that women have been widely under-represented in cardiovascular clinical trials. Moreover, a significant discrepancy in pharmacological and interventional strategies has been reported. Therefore, poor outcomes and more significant mortality have been shown in many diseases. Pharmacokinetic and pharmacodynamic differences in drug metabolism have also been described so that effectiveness could be different according to sex. However, awareness about the gender gap remains too scarce. Consequently, gender-specific guidelines are lacking, and the need for a sex-specific approach has become more evident in the last few years. This paper aims to evaluate different therapeutic approaches to managing the most common women's diseases.

Associazione Nazionale Medici Cardiologi Ospedalieri (ANMCO) scientific statement on the simplification of the drug regimen for secondary cardiovascular prevention.

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 Associazione Nazionale Medici Cardiologi Ospedalieri (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 socio-economic 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.

Cardio-oncology rehabilitation: are we ready?

Cardio-oncology rehabilitation (CORE) is not only an essential component of cancer rehabilitation but also a pillar of preventive cardio-oncology. Cardio-oncology rehabilitation is a comprehensive model based on a multitargeted approach and its efficacy has been widely documented; when compared with an 'exercise only' programme, comprehensive CORE demonstrates a better outcome. It involves nutritional counselling, psychological support, and cardiovascular (CV) risk assessment, and it is directed to a very demanding population with a heavy burden of CV diseases driven by physical inactivity, cancer therapy-induced metabolic derangements, and cancer therapy-related CV toxicities. Despite its usefulness, CORE is still underused in cancer patients and we are still at the dawning of remote models of rehabilitation (tele-rehabilitation). Not all CORE is created equally: 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 paper is to provide an updated review of CORE not only for cardiologists dealing with this peculiar population of patients 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.

[STEP-RCV Project - A scientific expert panel for patients at high and very high cardiovascular risk: how to streamline lipid-lowering therapy]. / STEP-RCV Project: ScienTific Expert Panel per i pazienti a rischio cardiovascolare alto e molto alto: come ottimizzare la terapia ipolipemizzante.

Over the last decade, several innovative therapeutic options have been developed and marketed for the management of hypercholesterolemia. However, the impossibility of a contextual update of international guidelines and the limits imposed by national regulatory authorities do not allow the use of these treatments in many patients, in particular in those at higher cardiovascular risk. Real-world studies show that the use of lipid-lowering therapies is inadequate even among patients at higher cardiovascular risk, with only 20% achieving recommended low-density lipoprotein cholesterol (LDL-C) levels and the use of combination therapies implemented in only 24% of patients. This review aims to highlight the benefits of an approach based on combination therapy and to propose a therapeutic algorithm that includes oral combination therapy, where necessary also in triple association (statin, ezetimibe and bempedoic acid), as an initial approach based on the most favorable cost-effectiveness ratio for patients at higher cardiovascular risk and the use of injectable anti-proprotein convertase subtilisin/kexin 9 therapies if the recommended LDL-C goal is not achieved.

[ANMCO Position paper: Obesity in adults - A clinical primer]. / Position paper ANMCO: Obesità nell'adulto ­ Clinical primer.

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.

[ANMCO Scientific statement on combination therapies and polypill in secondary prevention]. / Scientific statement ANMCO sulla semplificazione del regime terapeutico farmacologico in prevenzione secondaria.

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.

Heart Failure with Preserved Ejection Fraction: How to Deal with This Chameleon.

Heart failure with preserved ejection fraction (HFpEF) is characterized by a notable heterogeneity in both phenotypic and pathophysiological features, with a growing incidence due to the increase in median age and comorbidities such as obesity, arterial hypertension, and cardiometabolic disease. In recent decades, the development of new pharmacological and non-pharmacological options has significantly impacted outcomes, improving clinical status and reducing mortality. Moreover, a more personalized and accurate therapeutic management has been demonstrated to enhance the quality of life, diminish hospitalizations, and improve overall survival. Therefore, assessing the peculiarities of patients with HFpEF is crucial in order to obtain a better understanding of this disorder. Importantly, comorbidities have been shown to influence symptoms and prognosis, and, consequently, they should be carefully addressed. In this sense, it is mandatory to join forces with a multidisciplinary team in order to achieve high-quality care. However, HFpEF remains largely under-recognized and under-treated in clinical practice, and the diagnostic and therapeutic management of these patients remains challenging. The aim of this paper is to articulate a pragmatic approach for patients with HFpEF focusing on the etiology, diagnosis, and treatment of HFpEF.