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.

Renal effects of SGLT2 inhibitors in cardiovascular patients with and without chronic kidney disease: focus on heart failure and renal outcomes.

The kidney has a prominent role in maintaining glucose homeostasis by using glucose as a metabolic substrate. This occurs by generating glucose through gluconeogenesis, and by reuptaking filtered glucose through the sodium-glucose cotransporters SGLT1 and SGLT2 located in the proximal tubule. In recent studies, the administration of sodium-glucose cotransporters inhibitors demonstrated that inhibition of renal glucose reabsorption significantly reduces adverse renal events and heart failure exacerbations, in type 2 diabetic patients with and without cardiovascular damage as well as in advanced chronic kidney disease and heart failure patients with reduced ejection fraction with and without diabetes. The benefit was consistent throughout the different investigated clinical conditions, ameliorating overall patient outcome. The efficacy of sodium glucose cotransporters inhibitors was prominently linked to the limitation of renal damage as highlighted by the significant reduction on global mortality achieved in the studies investigating diabetic and not diabetic populations with advanced chronic kidney disease. Both studies were halted at the interim analysis because of unquestionable evidence of treatment benefit. In current review, we examine the role of SGLT2 and SGLT1 in the regulation of renal glucose reabsorption in health and disease and the effect of SGLT2 inhibition on clinical outcomes of populations with different cardiovascular conditions investigated with large-scale outcome trials.

The Key Role of a Psychoactive Substance Use History in Comprehensive Cardiovascular Risk Assessment, Diagnosis, Treatment, and Prevention.

BACKGROUND: Psychoactive substances have toxic effects resulting different cardiovascular and non-cardiovascular organ damage. Through a variety of mechanisms, they can trigger the onset of various forms of cardiovascular disease: acute or chronic, transient or permanent, subclinical or symptomatic. Hence, a thorough knowledge of the patient's drug habits is essential for a more complete clinical-etiopathogenetic diagnosis and consequent therapeutic, preventive, and rehabilitative management. SUMMARY: The prime reason for taking a psychoactive substance use history in the cardiovascular context is to identify those people who use substances (whether habitual or occasional users, symptomatic or not) and adequately assess their overall cardiovascular risk profile in terms of "user status" and type of substance(s) used. A psychoactive substance history could also alert the physician to suspect, and eventually diagnose, cardiovascular disease related to the intake of psychoactive substances, so optimizing the medical management of users. This anamnesis could finally assess the likelihood of patients persisting in the habit as a user or relapse, while maintaining high their cardiovascular risk profile. Taking such a history should be mandatory when a causal connection is suspected between intake of psychoactive substances and the observed symptoms or pathology, regardless of whether the individual is a declared user or not. KEY MESSAGES: The purpose of this article was to provide practical information on when, how, and why to perform a psychoactive substance use history.

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 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.

Respiratory failure and bioelectrical phase angle are independent predictors for long-term survival in acute heart failure.

Background. The assessment of long-term mortality in acute decompensated heart failure (ADHF) is challenging. Respiratory failure and congestion play a fundamental role in risk stratification of ADHF patients. The aim of this study was to investigate the impact of arterial blood gases (ABG) and congestion on long-term mortality in patients with ADHF. Methods and results. We enrolled 252 patients with ADHF. Brain natriuretic peptide (BNP), blood urea nitrogen (BUN), phase angle as assessed by means of bioimpedance vector analysis, and ABG analysis were collected at admission. The endpoint was all-cause mortality. At a median follow-up of 447 d (interquartile range [IQR]: 248-667), 72 patients died 1-840 d (median 106, IQR: 29-233) after discharge. Respiratory failure types I and II were observed in 78 (19%) and 53 (20%) patients, respectively. The ROC analyses revealed that the cut-off points for predicting death were: BNP > 441 pg/mL, BUN > 1.67 mmol/L, partial pressure in oxygen (PaO2) ≤69.7 mmHg, and phase angle ≤4.9°. Taken together, these four variables proved to be good predictors for long-term mortality in ADHF (area under the curve [AUC] 0.78, 95% CI 0.72-0.78), thus explaining 60% of all deaths. A multiparametric score based on these variables was determined: each single-unit increase promoted a 2.2-fold augmentation of the risk for death (hazard ratio [HR] 2.2, 95% CI 1.8-2.8, p< .0001). Conclusions. A multiparametric approach based on measurements of BNP, BUN, PaO2, and phase angle is a reliable approach for long-term prediction of mortality risk in patients with ADHF.

The PONTE (PDTA FOR INTEGRATED FOLLOW-UP TERRITORY HOSPITAL OF THE PATIENT WITH CARDIAC HEART FAILURE) (BRIDGE) Heart Failure project: increased adherence to guideline-recommended therapies through web-based shared clinical database.

The aim of this study was to evaluate the effects on the adherence of drug prescription to the guideline recommendations of a chronic care model based on the close interaction between hospital and local healthcare district cardiologists through a shared web-based database. From 2018 to 2021, patients hospitalized for an episode of acute decompensated heart failure (HF) (de novo or worsening) in cardiology wards from the healthcare district of Bari, Italy, were enrolled. The follow-up programme was based on a first visit after discharge within 1 month; patients were therefore addressed to the local health district cardiologist outpatient clinics when not requiring further invasive investigations and haemodynamically stable and followed-up with at least one visit every 6 months. In order to share in-hospital patients' data with outpatient clinics, at discharge, they were entered in a web-based database accessible for all cardiologists and centres participating in the Ponte Project. The group of patients affected by HF with reduced ejection fraction (HFrEF) were considered for the analyses. Drug prescription rates at 1-year follow-up were analysed as endpoint, as well as the re-admission for HF worsening. Out of 1200 HF patients enrolled in the project until December 2021, 56% were affected by HFrEF. At 1-year follow-up, 91% of patients were assuming beta-blockers, 86% mineralocorticoid receptor antagonists, 98% angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists/neprilysin angiotensin receptor antagonists, and 13% ARNI. Compared to patients enrolled before 2020, ARNI prescription increased in 2021 (60% vs. 13%, respectively, P < 0.001). In 30% of patients, ARNI were prescribed before hospital discharge. Furthermore, in 10% of the population (most diabetics), sodium-glucose cotransporter 2 inhibitors were also prescribed. The implementation of the PONTE project was associated with an improved adherence to guidelines recommendations.

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.

ANMCO position paper on antithrombotic treatment of patients with atrial fibrillation undergoing intracoronary stenting and/or acute coronary syndromes.

Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) with or without acute coronary syndromes (ACS) represent a subgroup with a challenging pharmacological management. Indeed, if on the one hand, antithrombotic therapy should reduce the risk related to recurrent ischaemic events and/or stent thrombosis; on the other hand, care must be taken to avoid major bleeding events. In recent years, several trials, which overall included more than 12 000 patients, have been conducted demonstrating the safety of different therapeutic combinations of oral antiplatelet and anticoagulant agents. In the present ANMCO position paper, we propose a decision-making algorithm on antithrombotic strategies based on scientific evidence and expert consensus to be adopted in the periprocedural phase, at the time of hospital discharge, and in the long-term follow-up of patients with AF undergoing PCI with/without ACS.

The Benefit of Sodium-Glucose Co-Transporter Inhibition in Heart Failure: The Role of the Kidney.

In the essential homeostatic role of kidney, two intrarenal mechanisms are prominent: the glomerulotubular balance driving the process of Na+ and water reabsorption in the proximal tubule, and the tubuloglomerular feedback which senses the Na+ concentration in the filtrate by the juxtaglomerular apparatus to provide negative feedback on the glomerular filtration rate. In essence, the two mechanisms regulate renal oxygen consumption. The renal hyperfiltration driven by increased glomerular filtration pressure and by glucose diuresis can affect renal O2 consumption that unleashes detrimental sympathetic activation. The sodium-glucose co-transporters inhibitors (SGLTi) can rebalance the reabsorption of Na+ coupled with glucose and can restore renal O2 demand, diminishing neuroendocrine activation. Large randomized controlled studies performed in diabetic subjects, in heart failure, and in populations with chronic kidney disease with and without diabetes, concordantly address effective action on heart failure exacerbations and renal adverse outcomes.

The Impairment in Kidney Function in the Oral Anticoagulation Era. A Pathophysiological Insight.

The need for anticoagulation in patients with atrial fibrillation (AF) is fundamental to prevent thromboembolic events. Direct oral anticoagulants (DOACs) recently demonstrated to be superior, or at least equal, to Warfarin in reducing the risk for stroke/systemic embolism and preventing major bleeding and intracranial hemorrhages. The AF population often suffers from chronic kidney disease (CKD). Indeed, the relationship between AF and renal function is bidirectional: AF can trigger kidney failure, while kidney impairment can promote alterations able to enhance AF. Therefore, there are concerns regarding prescriptions of anticoagulants to patients with AF and CKD. The worsening in kidney function can be effectively due to anticoagulants administration. Warfarin has been recognized to promote acute kidney injury in case of excessive anticoagulation levels. Nevertheless, further mechanisms can induce the chronic worsening of renal function, thus leading to terminal kidney failure as observed in post-hoc analysis from registration trials and dedicated observational studies. By contrast, DOACs seem to protect kidneys from injuries more efficiently than Warfarin, although they still continue to play a role in promoting some kidney lesions. However, the exact mechanisms remain unknown. This narrative review aimed to discuss the influence of oral anticoagulants on renal impairment as well as to overview potential pathophysiological mechanisms related to this clinical complication.

ANMCO POSITION PAPER: on administration of type 2 sodium-glucose co-transporter inhibitors to prevent heart failure in diabetic patients and to treat heart failure patients with and without diabetes.

This ANMCO (Associazione Nazionale Medici Cardiologi Ospedalieri) position paper aims to analyse the complex action of sodium-glucose co-transporter 2 inhibitors at the level of the kidney and cardiovascular system, focusing on the effect that these molecules have shown in the prevention and treatment of heart failure in diabetic and non-diabetic subjects. The goal was pursued by comparing the data generated with pathophysiology studies and with multicentre controlled studies in large populations. In accordance with the analysis carried out in the document, the following recommendations are issued: (i) canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin are molecules recommended for the prevention of heart failure hospitalizations in type 2 diabetic subjects; (ii) canagliflozin and dapagliflozin are recommended for the prevention of heart failure hospitalizations in type 2 diabetic subjects with severe chronic kidney disease, dapagliflozin proved to be safe and effective also in diabetic subjects; and (iii) dapagliflozin and empagliflozin are recommended to reduce the combined risk of heart failure and cardiovascular death in diabetic and non-diabetic subjects with heart failure and reduced ejection fraction.

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.

ANMCO POSITION PAPER: The reorganization of cardiology in times of the SARS-CoV-2 pandemic.

The COVID-19 pandemic represents an unprecedented event that has brought deep changes in hospital facilities with reshaping of the health system organization, revealing inadequacies of current hospital and local health systems. When the COVID-19 emergency will end, further evaluation of the national health system, new organization of acute wards, and a further evolution of the entire health system will be needed to improve care during the chronic phase of disease. Therefore, new standards for healthcare personnel, more efficient organization of hospital facilities for patients with acute illnesses, improvement of technological approaches, and better integration between hospital and territorial services should be pursued. With experience derived from the COVID-19 pandemic,new models, paradigms, interventional approaches, values and priorities should be suggested and implemented.

ANMCO POSITION PAPER: Timing of coronary angiography in non-ST-segment elevation acute coronary syndromes.

The European Society of Cardiology guidelines on non-ST-elevation acute coronary syndromes suggest different temporal strategies for the angiographic study depending on the risk profile. The scientific evidence underlying the guideline recommendations and the critical issues currently existing in Italy, that often do not allow either an extended strategy of revascularization within 24 h or the application of the principle of the same day transfer from a spoke to a hub centre, are analysed. The position paper focuses, in particular, on the subgroup of patients with a defined diagnosis of non-ST-elevation myocardial infarction by proposing a timing of coronary angiography/revascularization that takes into account the available scientific evidence and the organizational possibilities of a considerable part of national cardiology services.

ANMCO POSITION PAPER: Role of intra-aortic balloon pump in patients with acute advanced heart failure and cardiogenic shock.

The treatment of patients with advanced acute heart failure is still challenging. Intra-aortic balloon pump (IABP) has widely been used in the management of patients with cardiogenic shock. However, according to international guidelines, its routinary use in patients with cardiogenic shock is not recommended. This recommendation is derived from the results of the IABP-SHOCK II trial, which demonstrated that IABP does not reduce all-cause mortality in patients with acute myocardial infarction and cardiogenic shock. The present position paper, released by the Italian Association of Hospital Cardiologists, reviews the available data derived from clinical studies. It also provides practical recommendations for the optimal use of IABP in the treatment of cardiogenic shock and advanced acute heart failure.

Prevalence, management, and outcome of adverse rhythm disorders in takotsubo syndrome: insights from the international multicenter GEIST registry.

One important complication related to takotsubo syndrome (TTS) is adverse rhythm disorders. Our study was conducted to determine the incidence and management of adverse rhythm disorders in TTS and its long-term prognostic impact. We analyzed 906 TTS patients from 9 European centers. Patients were divided into the adverse rhythm disorders group (encompassing ventricular tachycardia, ventricular fibrillation, torsade de pointes, and asystole or complete atrioventricular block) and non-adverse rhythm disorders group. In our study cohort, we identified 67 (7.4%) patients with presence of adverse rhythm disorders. TTS patients were followed up over a period of 2.8 years. In the adverse rhythm disorders group, 18% of patients presented adverse rhythm disorders before hospital admission. Asystole and/or AV block were significantly more presented before admission (13 patients versus 8 patients; p < 0.01), whereas ventricular tachyarrhythmias were more presented in-hospital (4 patients versus 42 patients; p < 0.01). Adverse rhythm disorders patients suffered more frequently from cardiogenic shock (31% versus 7.6%, p < 0.01) and in-hospital death (10.9% versus 3.6%; p < 0.01). Furthermore, the long-term survival was significantly impaired in adverse rhythm disorders patients as compared with non-adverse rhythm disorders patients; (log-rank p < 0.01). Using multivariate Cox regression analysis, cardiogenic shock (HR 2.86, 95% CI 1.1-6.9; p = 0.02) was identified as independent predictors of adverse rhythm disorders. The short- and long-term mortality rate of TTS patients presenting with adverse rhythm disorders was significantly higher than in TTS patients presenting without it. Therefore, TTS patients with adverse rhythm disorders should be carefully monitored during hospital stay and at long-term follow-up.

ANMCO POSITION PAPER: Network Organization for the Treatment of Acute Coronary Syndrome Patients during the Emergency COVID-19 Pandemic.

The COVID-19 pandemic has become a global health emergency. In Italy, the number of people infected by SARS-COVID-2 is rapidly increasing and what emerges from the current data is that the majority do not present any symptoms or only minor flu-like symptoms. In about 20% of the patients, the disease progresses towards more complex forms (interstitial pneumonia to acute respiratory distress and multiple organ failure) with the need of hospitalization in CICU and advanced ventilator assistance. The transmission of the virus occurs very easily from the symptomatic patient s droplets from coughing and sneezing and from direct contact with persons or surfaces. In a patient presenting with ST elevation (STEMI) myocardial infarction or STEMI-like, if positive to COVID-19, the reperfusion therapeutic strategy depends on the local organization and on the possibility to access without delay a PCI COVID Center, on the basis, obviously, of the risk/benefit assessment of the individual case. However, we advise to try pursuing, in the first instance, the mechanical revascularization strategy, according to the available local possibilities.

ANMCO POSITION PAPER: The management of suspect or confirmed COVID-19 patients needing urgent electrophysiology and/or electrostimulation procedures.

The aim of this document is the management and organization of patients in need of urgent access to electrophysiology (EP) and pacing procedures during the COVID-19 emergency. Specifically, non-deferrable procedures or irreplaceable with a drug therapy prior to the resolution of the COVID-19 virus emergency [pacemaker (PM) implant/replacement/urgent defibrillator (implantable cardioverter-defibrillator, ICD) or arrhythmic storm or other indication of non-deferrable ablation]. The pacing and electrophysiological procedures urgent as they may be, less and less frequently represent situations of emergency, therefore for almost all cases, it is possible to perform a swab test to determine the positivity to COVID-19 of the patient. In cases where this is not possible, due to situations of emergency, the recommendations and procedures we have indicated are advisable, if not mandatory, in order to avoid the spreading of the virus to healthcare personnel and other patients.