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.

[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.

[ANMCO Position paper in collaboration with ITACARE-P: Cardio-oncology rehabilitation. Are we ready?] / Position paper ANMCO in collaborazione con ITACARE-P: Riabilitazione cardio-oncologica. "Are we ready?".

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.

[Multidistrict atherosclerotic disease: epidemiological and clinical framework]. / Malattia aterosclerotica polidistrettuale: inquadramento epidemiologico e clinico.

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.

[ANMCO Position paper: States General 2023 - Scientific societies and training: the role of ANMCO]. / Position paper ANMCO: Stati Generali 2023 ­ Società scientifiche e formazione: il ruolo dell'ANMCO.

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.

[ANMCO Position paper: States General 2023 - Role of ANMCO in the setting of clinical research in Cardiology in Italy: current state and future perspectives]. / Position paper ANMCO: Stati Generali 2023 ­ Ruolo dell'ANMCO nella ricerca clinica cardiologica in Italia: attualità e prospettive.

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.

[ANMCO Position paper: States General 2023 - Digital medicine in cardiology: evidence and state of progress in Italy]. / Position paper ANMCO: Stati Generali 2023 ­ La medicina digitale in cardiologia: evidenze e stato di avanzamento in Italia.

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.

Working in interventional cardiology laboratories: The perceived impact of radiation exposure as a health and gender hazard. A NEXT generation ANMCO initiative.

BACKGROUND: Gender-related discrepancies in personal and professional life have been reported among radio-exposed workers. We assessed this topic among cardiac catheterization workers in Italy, with a focus on gender and working position. METHODS: Radio-exposed workers affiliated with the Italian Association of Hospital Cardiologists were invited to answer an online survey, which included 41 questions formatted as multiple choice. RESULTS: Overall, 237 workers responded. The proportion of males was significantly higher than that of females in the population aged >50 years. A greater portion of females than males perceived female-gender discrimination regarding career advancement (77.2% vs 30.9%, p < 0.001) and work compensation (49.1% vs. 17.1%, p < 0.001). There was no difference in perceived gender- discrimination in terms of career advancement opportunities between physician and non-physicians. A larger portion of females than males experienced workplace discrimination (51.8% of females vs. 8.1% of males, p < 0.0001). Non-physician responders made up 38.8% of all respondents and reported a lower yearly radiation exposure than physicians. Non-physicians were more aware of the laws regulating lab access during pregnancy than physicians (93.5% vs. 48.3%, p < 0.0001). A greater percentage of female nurses than physicians communicate without hesitation the pregnancy status to their employers (45.6% vs 20%, p < 0.001). CONCLUSIONS: Gender-based career disparities were perceived among physicians and non-physician staff of cardiology interventional laboratories. Strategies should be implemented to ensure gender equality in career opportunities and to increase knowledge of radioprotection and the laws regulating access to laboratories during pregnancy.

[Lipoprotein(a): relationships with atherosclerosis and valvular heart disease, and emerging therapies]. / Lipoproteina(a): associazione con la malattia aterosclerotica e valvolare e terapie emergenti.

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.

ANMCO (Italian Association of Hospital Cardiologists) scientific statement: obesity in adults-an approach for cardiologists.

Obesity is a complex, chronic disease requiring a multidisciplinary approach to its management. In clinical practice, body mass index and waist-related measurements can be used for obesity screening. The estimated prevalence of obesity among adults worldwide is 12%. With the expected further increase in overall obesity prevalence, clinicians will increasingly be managing patients with obesity. Energy balance is regulated by a complex neurohumoral system that involves the central nervous system and circulating mediators, among which leptin is the most studied. The functioning of these systems is influenced by both genetic and environmental factors. Obesity generally occurs when a genetically predisposed individual lives in an obesogenic environment for a long period. Cardiologists are deeply involved in evaluating patients with obesity. Cardiovascular risk profile is one of the most important items to be quantified to understand the health risk due to obesity and the clinical benefit that a single patient can obtain with weight loss. At the individual level, appropriate patient involvement, the detection of potential obesity causes, and a multidisciplinary approach are tools that can improve clinical outcomes. In the near future, we will probably have new pharmacological tools at our disposal that will facilitate achieving and maintaining weight loss. However, pharmacological treatment alone cannot cure such a complex disease. The aim of this paper is to summarize some key points of this field, such as obesity definition and measurement tools, its epidemiology, the main mechanisms underlying energy homeostasis, health consequences of obesity with a focus on cardiovascular diseases and the obesity paradox.Level of evidence V: report of expert committees.

[ANMCO Position paper - 2023 ANMCO States General: The shortage of healthcare personnel in the cardiology field]. / Position paper ANMCO ­ Stati Generali ANMCO 2023: La carenza del personale sanitario in ambito cardiologico.

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.

[Gender discrepancy: time to implement gender-based clinical management]. / Position paper ANMCO: Differenze di genere nell'approccio farmacologico cardiovascolare.

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.

[ANMCO Position paper - 2023 ANMCO States General: Towards a modern Cardiological Community Care]. / Position paper ANMCO ­ Stati Generali ANMCO 2023: Verso una moderna Cardiologia Territoriale.

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.

Anderson-Fabry Disease: Red Flags for Early Diagnosis of Cardiac Involvement.

Anderson-Fabry disease (AFD) is a lysosome storage disorder resulting from an X-linked inheritance of a mutation in the galactosidase A (GLA) gene encoding for the enzyme alpha-galactosidase A (α-GAL A). This mutation results in a deficiency or absence of α-GAL A activity, with a progressive intracellular deposition of glycosphingolipids leading to organ dysfunction and failure. Cardiac damage starts early in life, often occurring sub-clinically before overt cardiac symptoms. Left ventricular hypertrophy represents a common cardiac manifestation, albeit conduction system impairment, arrhythmias, and valvular abnormalities may also characterize AFD. Even in consideration of pleiotropic manifestation, diagnosis is often challenging. Thus, knowledge of cardiac and extracardiac diagnostic "red flags" is needed to guide a timely diagnosis. Indeed, considering its systemic involvement, a multidisciplinary approach may be helpful in discerning AFD-related cardiac disease. Beyond clinical pearls, a practical approach to assist clinicians in diagnosing AFD includes optimal management of biochemical tests, genetic tests, and cardiac biopsy. We extensively reviewed the current literature on AFD cardiomyopathy, focusing on cardiac "red flags" that may represent key diagnostic tools to establish a timely diagnosis. Furthermore, clinical findings to identify patients at higher risk of sudden death are also highlighted.

Acute pulmonary embolism and cancer: findings from the COPE study.

BACKGROUND: Patients with acute venous thromboembolism associated with cancer have an increased risk of recurrences and bleeding in the long term. RESEARCH QUESTION: To describe the clinical features and short-term course of patients with acute pulmonary embolism (PE) and active cancer, previous cancer or no cancer. STUDY DESIGN AND METHODS: Patients with acute PE included in COPE-prospective, multicentre study of adult patients with acute, symptomatic, objectively diagnosed PE-were classified as having active cancer, previous cancer, or no cancer. RESULTS: Overall, 832 patients had active cancer, 464 with previous cancer and 3660 patients had no cancer at the time of acute PE. The most prevalent primary sites of active cancer were urogenital (23.0%), gastrointestinal (21.0%), and lung (19.8%), with a high prevalence of metastatic disease (57.6%) and ongoing anticancer treatment (16.2%). At discharge, a direct oral anticoagulant was used in 43.1%, 78.8%, and 82.0% of patients with active cancer, previous cancer, and no cancer, respectively. Rates of death in-hospital and at 30 days were higher in patients with active cancer compared to patients with previous cancer and no cancer (7.9% vs. 4.3% vs. 2.2% and 13.8% vs. 5.2% vs. 2.6%, respectively). Rates of major bleeding were 4.8%, 2.6%, and 2.4%, respectively. Among patients with active cancer, lung or metastatic cancer were independent predictors of death; brain, hematological or gastrointestinal cancer had the highest risk of major bleeding. INTERPRETATION: Among patients with acute PE, those with active cancer have high risks for death or major bleeding within 30 days. These risks vary based on primary site of cancer. CLINICAL TRIAL REGISTRATION: clinicaltrial.gov identifier: NCT03631810.