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.

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.

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.

The Challenge of Managing Atrial Fibrillation during Pregnancy.

The incidence of atrial fibrillation (AF) during pregnancy increases with maternal age and with the presence of structural heart disorders. Early diagnosis and prompt therapy can considerably reduce the risk of thromboembolism. The therapeutic approach to AF during pregnancy is particularly challenging, and the maternal and fetal risks associated with the use of antiarrhythmic and anticoagulant drugs must be carefully evaluated. Moreover, the currently used thromboembolic risk scores have yet to be validated for the prediction of stroke during pregnancy. At present, electrical cardioversion is considered to be the safest and most effective strategy in women with hemodynamic instability. Beta-selective blockers are also recommended as the first choice for rate control. Antiarrhythmic drugs such as flecainide, propafenone and sotalol should be considered for rhythm control if atrioventricular nodal-blocking drugs fail. AF catheter ablation is currently not recommended during pregnancy. Overall, the therapeutic strategy for AF in pregnancy must be carefully assessed and should take into consideration the advantages and drawbacks of each aspect. A multidisciplinary approach with a "Pregnancy-Heart Team" appears to improve the management and outcome of these patients. However, further studies are needed to identify the most appropriate therapeutic strategies for AF in pregnancy.

Prevalence and predictive role of hypertriglyceridemia in statin-treated patients at very high risk: Insights from the START study.

BACKGROUND AND AIM: Elevated triglyceride (TG) levels seem to identify subjects at increased cardiovascular risk, independent of LDL-C levels. We sought to evaluate the predictive role of hypertriglyceridemia, defined as TG levels ≥150 mg/dl, in very high risk (VHR) patients with chronic coronary syndromes (CCS) treated with statins. METHODS AND RESULTS: Using the data from the STable Coronary Artery Diseases RegisTry (START) study, an Italian nationwide registry, we assessed the association between the TG levels and baseline clinical characteristics, pharmacological treatment and major adverse cardio-cerebrovascular events (MACCE) at 1 year in a large cohort of statin-treated patients at VHR. Of the 4751 consecutive patients with CCS enrolled in the registry and classified as VHR, 2652 (55.8%) had TG values available (mean 120.6 ± 54.9) and were treated with at least a statin at baseline: 2019 (76.1%) with TG < 150 and 633 (23.9%) with TG ≥ 150 mg/dl. At 1 year from enrolment, MACCE occurred in 168 (6.3%) patients, without differences between the two groups of TG (5.9 vs 7.6%; p = 0.14). At multivariable analysis, hypertriglyceridemia did not result as independent predictor of the MACCE (hazard ratio: 1.16; 95% confidence intervals: 0.82-1.64; p = 0.42). CONCLUSIONS: In the present large, nationwide cohort of consecutive CCS patients at VHR with statin-controlled LDL-C levels, hypertriglyceridemia was present in around 24% of cases and did not result as predictor of MACCE at 1 year. Further studies with a longer follow-up and larger sample size are needed to better define the prognostic role of TG levels when intensive LDL lowering therapies are used.

Italian Association of Hospital Cardiologists practical guidance for sodium-glucose cotransporter 2 inhibitors use in patients with heart failure.

Sodium-glucose cotransporter 2 inhibitors (SGLT2-is) 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-is are well tolerated, it is important to know potential side effects and conditions that may lead to an increased risk of adverse events in order to maximize clinical benefits. The aim of this Italian Association of Hospital Cardiologists document is to briefly report clinical evidence that supports SGLT2-i use in patients with heart failure and provide practical indications for clinical implementation.

ANMCO-SIMEU consensus document: appropriate management of atrial fibrillation in the emergency department.

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 impact 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, in order to make it homogeneous across the national territory.

ANMCO position paper: guide to the appropriate use of the wearable cardioverter defibrillator in clinical practice for patients at high transient risk of sudden cardiac death.

Extended risk stratification and optimal management of patients with a permanently increased risk of sudden cardiac death (SCD) are 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 if there will be a significant recovery of function. It is important to protect the patients while receiving and titrating to the optimal dose the recommended drugs that may lead 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, and 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.

ANMCO position paper on vericiguat use in heart failure: from evidence to place in therapy.

In the growing therapeutic armamentarium for heart failure (HF) management, vericiguat represents an innovative therapeutic option. The biological target of this drug is different from that of other drugs for HF. Indeed, vericiguat does not inhibit neuro-hormonal systems overactivated in HF or sodium-glucose co-transporter 2 but stimulates the biological pathway of nitric oxide and cyclic guanosine monophosphate, which is impaired in patients with HF. Vericiguat has recently been approved by international and national regulatory authorities for the treatment of patients with HF and reduced ejection fraction who are symptomatic despite optimal medical therapy and have worsening HF. This ANMCO position paper summarises 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.

ANMCO position paper on the management of hypercholesterolaemia in patients with acute coronary syndrome.

Patients suffering from acute coronary syndrome (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 LDL-C levels decrease linearly correlates 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, Italian Association of Hospital Cardiologists 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 hypercholesterolaemia and the available therapeutic options, considering current reimbursement criteria.

Inclisiran: A New Pharmacological Approach for Hypercholesterolemia.

Therapeutic approaches based on gene silencing technologies represent a new opportunity to manage hypercholesterolemia. Inclisiran is a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA. Clinical studies have demonstrated that inclisiran is effective, safe, and well-tolerated in reducing low-density lipoprotein cholesterol (LDL-C) in patients with familial hypercholesterolemia, atherosclerotic cardiovascular disease, and atherosclerotic cardiovascular disease risk equivalents. A meta-analysis of phase 3 trials demonstrated a 51% reduction in LDL-C levels at 18 months as compared with placebo. Adverse event incidence was found to be comparable in individuals treated with inclisiran and those receiving placebo, though the reactions at the site of injection were more common in patients receiving inclisiran as compared with those receiving placebo. The recommended inclisiran dose is 284 mg administered as a subcutaneous injection to be repeated after three months with a subsequent 6-month maintenance regimen. Overall, since the pharmacological efficacy of inclisiran in LDL-C reduction is comparable to that of monoclonal antibodies against PCSK9, the longer effect duration and the favorable safety profile may favor this newer approach for hypercholesterolemia management.

Incidence, Characteristics, and Management of Patients with Recurrent Myocardial Infarctions: Insights from the EYESHOT POST-MI.

Background: It is unknown whether patients who survived two or multiple episodes of myocardial infarction (MI) present different clinical characteristics and management than patients at their first MI. Methods: The EYESHOT post-MI was a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. In 3 months of enrolment, 165 Italian cardiology centers included 1633 consecutive post-MI patients. In the present analysis, we stratified the study cohort according to the number of prior MI episodes (i.e., 1, 2 or ≥3). Results: Among the 1618 patients enrolled with complete data on MI history, 1335 (82.5%) were at their first MI episode, 209 (12.9%) had a history of 2 MIs, and the remaining 74 (4.6%) had ≥ 3 prior MIs. Patients with a history of multiple MIs were increasingly older and presented a significantly higher rate of risk factors compared to those at their first MI. During the year prior to enrolment, patients with 2 or ≥3 MI episodes more frequently underwent coronary angiography compared to the other group (p < 0.0001). In addition, several lifesaving and antianginal drugs were more frequently prescribed in patients presenting with a history of multiple MIs compared to those at their first MI. Conclusions: Our data suggest that patients with multiple MIs managed by cardiologists in routine clinical practice present an incremental clinical risk, more frequently undergo coronary angiography, and are more intensively managed with pharmacological therapies compared to patients at their first MI episode.

Could the PARIS Risk Scores Be Useful for the Choice of Triple versus Dual Antithrombotic Therapy in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention?

INTRODUCTION: Current guidelines recommend dual antithrombotic therapy (DAT) for the majority of patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) and suggest a short course of triple antithrombotic therapy (TAT) for those at very high thrombotic risk (TR) but low bleeding risk (BR). METHODS: We analyze if the PARIS ischemic-hemorrhagic scale could be useful for the choice of antithrombotic strategy in patients with acute coronary syndromes and AF treated with coronary stenting enrolled in the prospective, observational, nationwide MATADOR-PCI study. RESULTS: Among the 588 patients discharged alive, a TAT was prescribed in 381 (64.8%) and DAT in 52 (8.8%) patients. According to the PARIS scoring system, 142 (24.2%) were classified as low, 244 (41.5%) as intermediate, and 292 (34.3%) as high TR. In parallel, 87 (14.8%) were categorized in the low, 260 (44.2%) in the intermediate, and 241 (41.0%) in the high-risk stratum for major bleedings. Crossing the various strata of the two PARIS risk scores, the largest group of patients consisted of those at high TR and BR (n = 130, 22%), followed by those at intermediate risk according to both scores (n = 122, 21%). At discharge, TAT was mainly used in patients at intermediate to high BR, while DAT in those at intermediate to high TR but low BR, according to the PARIS score. CONCLUSION: Our data suggest that some variables associated with increased TR or BR are poorly considered in the daily practice, while the use of PARIS scales could help in the implementation of guidelines' recommendations.

ANMCO position paper: 2022 focused update of appropriate use criteria for multimodality imaging: aortic valve disease.

This document addresses the evaluation of the Appropriate Use Criteria (AUC) of multimodality imaging in the diagnosis and management of aortic valve disease. The goal of this AUC document is to provide a comprehensive resource for multimodality imaging in the context of aortic valve disease, encompassing multiple imaging modalities. Clinical scenarios are developed in a simple way to illustrate patient presentations encountered in everyday practice.

ANMCO position paper 'Appropriateness of prescribing direct oral anticoagulants in stroke and systemic thromboembolism prevention in adult patients with non-valvular atrial fibrillation'.

The appropriateness of prescribing direct oral anticoagulants [dabigatran, rivaroxaban, apixaban, and edoxaban (DOACs)] is regulated on the criteria established in Phase III trials. These criteria are reported in the summary of the product characteristics of the four DOACs. In clinical practice, prescriptions are not always in compliance with established indications. In particular, the use of lower doses than those recommended in drug data sheets is not uncommon. Literature data show that the inappropriate prescription of reduced doses causes drug underexposure and up to a three-fold increase in the risk of stroke/ischaemic transient attack, systemic thromboembolism, and hospitalization. Possible causes of the deviation between the dose that should be prescribed and that prescribed in the real world include erroneous prescription, an overstated haemorrhagic risk perception, and the presence of frail and complex patients in clinical practice who were not included in pivotal trials, which makes it difficult to apply study results to the real world. For these reasons, we summarize DOAC indications and contraindications. We also suggest the appropriate use of DOACs in common clinical scenarios, in accordance with what international guidelines and national and international health regulatory bodies recommend.

ANMCO statement on the use of sodium-glucose cotransporter 2 inhibitors in patients with heart failure: a practical guide for a streamlined implementation.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, dapagliflozin, and empagliflozin, first developed as glucose-lowering agents for the treatment of Type 2 diabetes, have been demonstrated to improve prognosis in patients with heart failure and reduced ejection fraction (HFrEF) regardless of the presence of diabetes. Since these drugs have only recently been included among the four pillars of HFrEF treatment, cardiologists are still unfamiliar with their use in this setting. This article provides an up-to-date practical guide for the initiation and monitoring of patients treated with SGLT2 inhibitors.

Do Pathophysiologic Mechanisms Linking Unhealthy Lifestyle to Cardiovascular Disease and Cancer Imply Shared Preventive Measures?　- A Critical Narrative Review.

Growing evidence has shown a bidirectional link between the cardiologic and oncologic fields. Several investigations support the role of unhealthy behaviors as pathogenic factors of both cardiovascular disease and cancer. We report epidemiological and research findings on the pathophysiological mechanisms linking unhealthy lifestyle to cardiovascular disease and cancer. For each unhealthy behavior, we also discuss the role of preventive measures able to affect both cardiovascular disease and cancer occurrence and progression.

Comparing the Prognostic Impact of Prediabetes with Diabetes in a Nationwide Cohort of Patients with Chronic Coronary Syndromes: An Analysis of the START Registry.

AIMS: Using data from the nationwide prospective START registry that enrolled a large cohort of patients with chronic coronary syndromes (CCS), we aimed to investigate whether the presence of diabetes mellitus (DM) and pre-DM independently affected the risk of cardiovascular events at 1-year follow-up. METHODS: We assessed the impact of DM and pre-DM on all-cause mortality and a composite of all-cause mortality and hospitalization for cardiovascular causes at 1-year follow-up. RESULTS: Among the 3,778 patients with available fasting plasma glucose data at study entry, 37% were classified as DM, 25% as pre-DM, and 38% as no DM. At 1 year, patients with DM had higher rates of all-cause death (p = 0.004) and death/cardiovascular hospitalization (p = 0.003) than those with pre-DM or without DM. Conversely, no significant differences in the adverse event rate were found between patients with pre-DM and those without DM. At unadjusted Cox analysis, DM resulted as a predictor of both death for any cause (hazard ratio [HR]: 2.41; 95% confidence intervals [CI]: 1.34-4.34; p = 0.003) and all-cause death/hospitalization for cardiovascular causes (HR: 1.29; 95% CI: 1.02-1.62; p = 0.03). However, DM did not result as an independent predictor of either endpoint at multivariate analysis. CONCLUSIONS: The risk of 1-year major events among patients with CCS and pre-DM is comparable to that of patients with CCS and normoglycemic status and is lower than that of patients with DM.

Pathophysiology and clinical presentation of paediatric heart failure related to congenital heart disease.

Congenital heart disease (CHD) and cardiomyopathies represent the two most important causes of paediatric heart failure (HF) in developed countries. We made a review of the literature on pathophysiology and clinical presentation of paediatric HF in children with CHD. Two main pathophysiologic models can be identified: the 'over-circulation failure', characterised by signs and symptoms of congestion or hypoperfusion, due respectively to volume or pressure overload, and the 'pump failure'. CONCLUSIONS: The comprehension of the HF pathophysiology in paediatric patients with CHD is of paramount importance for the optimal management and for addressing the best therapeutic choices.

ANMCO POSITION PAPER: Use of sacubitril/valsartan in hospitalized patients with acute heart failure.

Sacubitril/valsartan (S/V) has been shown to reduce the risk of cardiovascular death or heart failure hospitalization and improve symptoms in chronic heart failure with reduced ejection fraction compared with enalapril. After 7 years since the publication of the results of PARADIGM-HF, further insight has been gained with potential new indications. Two prospective randomized multicentre studies (PIONEER-HF and TRANSITION) in patients hospitalized for acute heart failure (AHF) have shown an improved clinical outcome and biomarker profile as compared with enalapril, and good tolerability, safety, and feasibility of initiating in-hospital administration of S/V. Furthermore, some studies have highlighted the favourable effects of S/V in attenuating adverse myocardial remodelling, supporting an early benefit after treatment. Observational data from non-randomized studies in AHF report that in-hospital and pre-discharge prescription of evidence-based drugs associated with better survival still remain suboptimal. Additionally, the COVID-19 pandemic has also negatively impacted on outpatient activities. Therefore, hospitalization, a real crossroad in the history of heart failure, must become a management and therapeutic opportunity for our patients. The objective of this ANMCO position paper is to encourage and facilitate early S/V administration in stabilized patients during hospitalization after an AHF episode, with the aim of improving care efficiency and clinical outcome.