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.

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.

Switching between direct oral anticoagulants: a systematic review and meta-analysis.

Crossover between direct oral anticoagulants (DOACs) has been underinvestigated, but happens frequently in clinical practice. It is still unknown whether DOACs have similar rates of switch, or whether some DOACs are more prone to be switched over time. We reviewed studies comparing DOAC-to-DOAC switch prevalence, and compared risk of switch depending on index DOAC through meta-analysis. Systematic review followed PRISMA guidelines and deposited protocol (PROSPERO#CRD42020152405). MEDLINE, EMBASE, and Cochrane-CENTRAL were searched up to 1/3/2020 for studies reporting on DOAC-to-DOAC switch. We determined by meta-analysis the pooled odds ratio (OR) for switch depending on index DOAC prescribed. Newcastle-Ottawa Scale was used for bias assessment. Among 221 results retrieved, 5 large studies (n = 259,308, mean age ranging 61.2-79.3) provided data on DOAC-to-DOAC switch. Studies were all large retrospective, observational and claims registry-based, with similar ascertainment of exposure and switch. Bias assessment revealed fair to high quality. Among DOACs, apixaban had consistently lower risk of DOAC-to-DOAC switch compared to dabigatran (OR 0.29, 95% CI 0.25-0.34) or rivaroxaban (OR 0.58, 95% CI 0.50-0.67), the former carrying a higher risk than the latter (OR 2.35, 95% CI 1.93-2.86). Results were robustly confirmed by sensitivity analysis. Apixaban might carry a lower risk of DOAC-to-DOAC switch compared to dabigatran and rivaroxaban. Further studies are needed to confirm long-term safety and effectiveness of switching paradigm.

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: 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.

ANMCO POSITION PAPER: The role of cardiology in the management of the health needs in the post-Covid-19 era.

At the end of 2019 a new Coronavirus appeared in China and, from there, it spread to the rest of the world. On 24th May, 2020, the confirmed cases in the world were more than 5 million and the deaths almost 350.000. At the end of May, Italy reported more than 27.000 cases among healthcare professionals and 163 deaths among physicians. The National Health Systems from almost all over the world, including Italy's, were unprepared for this pandemic, and this generated important consequences of organizational nature. All elective and urgent specialized activities were completely reorganized, and many hospital units were partially or completely converted to the care of the COVID-19 patients. A significant reduction in hospital admissions for acute heart disease were recorded during the SARS-CoV-2 pandemic and, in order to gradually resume hospital activities, the Italian National Phase 2 Plan for the partial recovery of activities, must necessarily be associated with a Phase 2 Health Plan. In regards to the cardiac outpatient activities we need to identify short term goals, i.e. reschedule the suspended outpatient activities, revise the waiting lists, review the 'timings' of the bookings. This will reduce the number of available examinations compared to the pre-Covid-19 era. The GP's collaboration could represent an important resource, a structured telephone follow-up plan is advisable with the nursing staff's involvement. It is equally important to set medium-long term goals, the pandemic could be an appropriate moment for making a virtue of necessity. It is time to reason on prescriptive appropriateness, telemedicine implementation intended as integration to the traditional management. It is time to restructure the cardiological units related to the issue of structural adjustment to the needs for functional isolation. Moreover, the creation of 'grey zones' with multidisciplinary management according to the intensity of care levels seems to be necessary as well as the identification of Covid dedicated cardiologies. Finally, the pandemic could represent the opportunity for a permanent renovation of the cardiological and territorial medicine activities.

ANMCO POSITION PAPER: The cardiological clinical activities in the transition phase of the COVID-19 pandemic.

Infections by SARS CoV2 - COVID-19 became in a short time a worldwide health emergency. The present SARS-CoV-2 pandemic induced in a short time, an unprecedented impact on public health and on the pre-existing care pathways. In order to appropriately address this epidemiological emergency, urgent solutions were needed, such as remodelling or stopping hospitalization and deferrable clinical activities to avoid spreading the SARS-CoV-2 infection. After the first emergency lockdown phase, care pathways must guarantee healthcare to patients and preserve the safety of the healthcare personnel and of all the other subjects that refer to the cardiological surgeries. Rigorous prescriptive appropriateness of the requested exams with consequent reduction of unnecessary examinations is an essential requirement to preserve prioritized diagnostic and care pathways to patients in need, minimizing the risks connected to the SARS-CoV-2 contagion in hospitals. Telemedicine services represent a valid answer to cardiovascular disease patients' need for care and assistance, including those in quarantine and voluntary isolation. These services successfully contribute to fight the spread of the virus guaranteeing at the same time therapy and support through remote services that must therefore be considered a resource to be implemented and enhanced. This document has to be used by the healthcare personnel working in hospitals and in district offices, if applicable, and aims at managing patients, in complete safety and considered not suspect/not probable ('not at risk') of SARS-CoV-2 infection, eligible for diagnostic activity and subsequent therapy in outpatient surgeries. In particular, this document provides indications for patient evaluation to prevent COVID-19 exposure, gives general indications on managing appointments and waiting rooms, on how to strictly adhere to environmental safety measures, on the proper use of Individual Protective Equipment (IPE). It also provides specific indications for outpatient service procedures, like electrocardiogram, cardiologic examination, cardiologic checkup, Dynamic Holter Electrocardiogram, Transthoracic Echocardiography, Echo Stress, Transoesophageal Echocardiography, Bike Ergometer stress test, Ergospirometry, Outpatient Checkup of implantable electronic cardiac devices.

ANMCO POSITION PAPER: Considerations on in-hospital cardiological consultations and cardiology outpatient clinics during the COVID-19 pandemic.

Infections by SARS CoV2 - COVID-19 have become in a short time a worldwide health emergency. Due to cardiovascular implications of COVID-19 and to very frequent previous cardiovascular disorders of COVID-19 patients, it is presently crucial that Cardiologists are fully aware of COVID-19 related epidemiological, pathophysiological and therapeutic problems, in order to manage at best the present emergency by appropriate protocols developed on the basis of the competences acquired and shared on the field. The aim of this document is to propose algorithms for the management of cardiovascular diseases during COVID-19 emergency with the objective of providing patients with optimal care, minimizing contagion risk and appropriately managing personal protective equipment.

Consensus Document ANMCO/ANCE/ARCA/GICR-IACPR/GISE/SICOA: Long-term Antiplatelet Therapy in Patients with Coronary Artery Disease.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor is the cornerstone of pharmacologic management of patients with acute coronary syndrome (ACS) and/or those receiving coronary stents. Long-term (>1 year) DAPT may further reduce the risk of stent thrombosis after a percutaneous coronary intervention (PCI) and may decrease the occurrence of non-stent-related ischaemic events in patients with ACS. Nevertheless, compared with aspirin alone, extended use of aspirin plus a P2Y12 receptor inhibitor may increase the risk of bleeding events that have been strongly linked to adverse outcomes including recurrent ischaemia, repeat hospitalisation and death. In the past years, multiple randomised trials have been published comparing the duration of DAPT after PCI and in ACS patients, investigating either a shorter or prolonged DAPT regimen. Although the current European Society of Cardiology guidelines provide a backup to individualised treatment, it appears to be difficult to identify the ideal patient profile which could safely reduce or prolong the DAPT duration in daily clinical practice. The aim of this consensus document is to review contemporary literature on optimal DAPT duration, and to guide clinicians in tailoring antiplatelet strategies in patients undergoing PCI or presenting with ACS.

ANMCO Position Paper: hospital discharge planning: recommendations and standards.

The hospital discharge is often poorly standardized and affected by discontinuity and fragmentation of care, putting patients at high risk of both post-discharge adverse events and early readmission. The present ANMCO document reviews the modifiable components of the hospital discharge process related to adverse events or re-hospitalizations and suggests the optimal methods for redesigning the whole discharge process. The key principles for proper hospital discharge or transfer of care acknowledge that the hospital discharge: • is not an isolated event, but a process that has to be planned as soon as possible after the admission, ensuring that the patient and the caregiver understand and contribute to the planned decisions, as equal partners; • is facilitated by a comprehensive systemic approach that begins with a multidimensional evaluation process; • must be organized by an operator who is responsible for the coordination of all phases of the hospital patient journey, involving afterward the general practitioner and transferring to them the information and responsibility at discharge; • is the result of an integrated multidisciplinary team approach; • appropriately uses the transitional and intermediate care services; • is carried out in an organized system of care and continuum of services; and • programs the passage of information to after-discharge services.

Risk-adjustment models for heart failure patients' 30-day mortality and readmission rates: the incremental value of clinical data abstracted from medical charts beyond hospital discharge record.

BACKGROUND: Hospital discharge records (HDRs) are routinely used to assess outcomes of care and to compare hospital performance for heart failure. The advantages of using clinical data from medical charts to improve risk-adjustment models remain controversial. The aim of the present study was to evaluate the additional contribution of clinical variables to HDR-based 30-day mortality and readmission models in patients with heart failure. METHODS: This retrospective observational study included all patients residing in the Local Healthcare Authority of Bologna (about 1 million inhabitants) who were discharged in 2012 from one of three hospitals in the area with a diagnosis of heart failure. For each study outcome, we compared the discrimination of the two risk-adjustment models (i.e., HDR-only model and HDR-clinical model) through the area under the ROC curve (AUC). RESULTS: A total of 1145 and 1025 patients were included in the mortality and readmission analyses, respectively. Adding clinical data significantly improved the discrimination of the mortality model (AUC = 0.84 vs. 0.73, p < 0.001), but not the discrimination of the readmission model (AUC = 0.65 vs. 0.63, p = 0.08). CONCLUSIONS: We identified clinical variables that significantly improved the discrimination of the HDR-only model for 30-day mortality following heart failure. By contrast, clinical variables made little contribution to the discrimination of the HDR-only model for 30-day readmission.

[Cardiologic evaluation of patients undergoing chemotherapy]. / La consulenza cardiologica "mirata" nel paziente oncologico sottoposto a chemioterapia: come prevenire e monitorare la cardiotossicità in maniera appropriate.

Life expectancy in patients affected by cancer has recently increased because of early diagnosis and actual therapies. In recent years, Oncology and Cardiology developed a tight relationship because of common risk factors (i.e., obesity, smoking, alcool intake, etc...), and for preventing the prothrombotic status due to cancer and the potential cardiotoxicity of chemotherapy. Cardiotoxicity incidence is reported from 1% up to 70% in retrospective analyses of drug protocols, mainly representing by left ventricular dysfunction (both reversible or irreversible), but also by arrhythmias, hypertension, atrioventricular block, coronary spasm, and arterial or venous thromboembolism. The early detection of the chemoterapy induced cardiotoxicity is now mandatory and can be obtained through a proper patients selection for different treatments and a strict monitoring during the follow-up period. The role of biomarkers of early cardiac damage, mainly, troponin I and brain natriuretic peptide-BNP, has been recently challenged, and algorithms are currently available. In the present paper, we propose how to perform a cardiological evaluation of patients undergoing chemotherapy tailored by the known adverse effects of the drugs.

Healthcare needs in elderly patients with chronic heart failure in view of a personalized blended collaborative care intervention: a cross sectional study.

Introduction: Few studies explored healthcare needs of elderly heart failure (HF) patients with comorbidities in view of a personalized intervention conducted by Care Managers (CM) in the framework of Blended Collaborative Care (BCC). The aims of the present study were to: (1) identify perceived healthcare needs/preferences in elderly patients with HF prior to a CM intervention; (2) investigate possible associations between healthcare needs/preferences, sociodemographic variables (age; sex) and number of comorbidities. Method: Patients aged 65 years or more affected by HF with at least 2 medical comorbidities were enrolled in the study. They were assessed by structured interviewing with colored cue cards that represented six main topics including education, individual tailoring of treatment, monitoring, support, coordination, and communication, related to healthcare needs and preferences. Results: Thirty-three patients (Italy = 21, Denmark = 7, Germany = 5; mean age = 75.2 ± 7.7 years; males 63.6%) were enrolled from June 2021 to February 2022. Major identified needs included: HF information (education), patients' involvement in treatment-related management (individual tailoring of treatment), regular checks of HF symptoms (monitoring), general practitioner update by a CM about progression of symptoms and health behaviors (coordination), and telephone contacts with the CM (communication). Regarding communication modalities with a CM, males preferred phone calls (χ2 = 6.291, p = 0.043) and mobile messaging services (χ2 = 9.647, p = 0.008), whereas females preferred in-person meetings and a patient dashboard. No differences in needs and preferences according to age and number of comorbidities were found. Discussion: The findings highlight specific healthcare needs and preferences in older HF multimorbid patients, allowing a more personalized intervention delivered by CM in the framework of BCC.

[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.

[Long-term anticoagulation after perioperative atrial fibrillation: a challenging issue]. / Terapia anticoagulante a lungo termine dopo fibrillazione atriale perioperatoria: una sfida ancora aperta.

Postoperative atrial fibrillation (POAF) after cardiac surgery is frequent, has a 4 to 5-fold risk of recurrences, and a pathophysiology mainly linked to triggers, including pericardiectomy. The risk of stroke is increased, while long-term anticoagulation therapy, based on available retrospective studies, is recommended by the European Society of Cardiology guidelines with class IIb and level of evidence B. On the other hand, POAF after non-cardiac surgery is less frequent, has a pathophysiology linked to the substrate rather than to triggers, and increases the risk of stroke and death. So far, long-term anticoagulation therapy (preferably with direct oral anticoagulants) has a class IIa recommendation with level of evidence B. Short-term anticoagulation after cardiac surgery, in the face of "provoked" atrial fibrillation, a well-known topic in the field of venous thromboembolism that has never found application in the field of atrial fibrillation, is often adopted in clinical practice although without evidence. The ongoing randomized trials will partially answer some of our questions, but, unfortunately, the management of POAF will remain a grey area and the indication for anticoagulation should be tailored.