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.

Aspirin hypersensitivity: a practical guide for cardiologists.

Aspirin has been known for a long time and currently stays as a cornerstone of antithrombotic therapy in cardiovascular disease. In patients with either acute or chronic coronary syndromes undergoing percutaneous coronary intervention aspirin is mandatory in a dual antiplatelet therapy regimen for prevention of stent thrombosis and/or new ischaemic events. Aspirin is also currently a first-option antithrombotic therapy after an aortic prosthetic valve replacement and is occasionally required in addition to oral anticoagulants after implantation of a mechanical valve. Presumed or demonstrated aspirin hypersensitivity is a main clinical problem, limiting the use of a life-saving medication. In the general population, aspirin hypersensitivity has a prevalence of 0.6%-2.5% and has a plethora of clinical presentations, ranging from aspirin-exacerbated respiratory disease to anaphylaxis. Although infrequent, when encountered in clinical practice aspirin hypersensitivity poses for cardiologists a clinical dilemma, which should never be trivialized, avoiding-as much as possible-omission of the drug. We here review the epidemiology of aspirin hypersensitivity, provide an outline of pathophysiological mechanisms and clinical presentations, and review management options, starting from a characterization of true aspirin allergy-in contrast to intolerance-to suggestion of desensitization protocols.

[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.

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.

Achievement of target LDL-cholesterol level in patients with acute coronary syndrome undergoing percutaneous coronary intervention: The JET-LDL registry.

BACKGROUND: In patients with acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level < 1.4 mmol/L (<55 mg/dL). METHODS: The JET-LDL is a multicenter, observational, prospective registry created to investigate levels of LDL-C in consecutive patients with ACS undergoing PCI at 35 Italian hospitals, and to report their lipid lowering therapies (LLT). Follow-up was planned at 1 and 3 months. LDL-C reduction >50% from baseline or level < 55 mg/dL at 1-month was the primary endpoint. RESULTS: A total of 1095 patients were included: median age was 67 (58-75); 33.7% were already on LLT. Baseline LDL-C levels was 105 (76.5-137) mg/dL. At hospital discharge all patients were on LLT: 98.1% received statins (as mono or combination therapy), ezetimibe and PCSK9i were used in 60.1% and 8.5% of cases, respectively. Primary endpoint was achieved in 62% (95% CI 58-65) of cases. At 1-month LDL-C levels dropped to 53 (38-70) mg/dL (p < 0.001 vs baseline) and it was <55 mg/dL in 53% (95% CI 49-57) of patients; however, PCSK9i were added to 7 further cases. At 3-months 58% (95% CI 55-62) of patients achieved the target level, but PCSK9i was added to only 11 new patients. CONCLUSIONS: In this real-world registry of ACS patients undergoing PCI, recommend LDL-C levels were obtained in 62% of patients, but PCSK9i prescription was limited to 10% of cases. As LLT pattern appeared mainly improved at hospital discharge, an early and strong treatment should be considered.

[ANMCO Position paper: Ionizing radiation exposure and radioprotection in the cath-lab]. / Position paper ANMCO: Radioesposizione e radioprotezione nei laboratori di cardiologia interventistica.

In the last decades, because of the improvements in the percutaneous treatment of coronary heart disease, valvular heart disease, congenital heart defects, and the increasing number of cardiac resynchronization therapy and cardioverter-defibrillator implantations, the interventional cardiologists' radio-exposure has importantly risen, causing concerns for ionizing radiation-associated diseases such as cancer and neurodegenerative disorders. Consequently, the radiation exposure issue importantly affects operators' safety. However, our knowledge of this field is poor and most operators are unaware to be at risk, especially because of the absence of effective preventive measures. The aim of this ANMCO position paper is to improve the awareness of operators and identify new ways of reducing operator ionizing radiation dose and minimizing the risk.

Management of Patients Treated with Direct Oral Anticoagulants in Clinical Practice and Challenging Scenarios.

It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug-drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios.

Management of Residual Risk in Chronic Coronary Syndromes. Clinical Pathways for a Quality-Based Secondary Prevention.

Chronic coronary syndrome (CCS), which encompasses a broad spectrum of clinical presentations of coronary artery disease (CAD), is the leading cause of morbidity and mortality worldwide. Recent guidelines for the management of CCS emphasize the dynamic nature of the CAD process, replacing the term "stable" with "chronic", as this disease is never truly "stable". Despite significant advances in the treatment of CAD, patients with CCS remain at an elevated risk of major cardiovascular events (MACE) due to the so-called residual cardiovascular risk. Several pathogenetic pathways (thrombotic, inflammatory, metabolic, and procedural) may distinctly contribute to the residual risk in individual patients and represent a potential target for newer preventive treatments. Identifying the level and type of residual cardiovascular risk is essential for selecting the most appropriate diagnostic tests and follow-up procedures. In addition, new management strategies and healthcare models could further support available treatments and lead to important prognostic benefits. This review aims to provide an overview of the diagnostic and therapeutic challenges in the management of patients with CCS and to promote more effective multidisciplinary care.

[Practical approach to the patient with fever in the intensive cardiac care unit: diagnostic framework and therapy notes]. / Approccio pratico al paziente con febbre in terapia intensiva cardiologica: inquadramento diagnostico e cenni di terapia.

The management of the patient with fever in the intensive cardiac care unit begins with a thorough evaluation of the patient, particularly symptoms, clinical history and physical examination, to provide information regarding the origin of the fever. The global evaluation of the patient should be integrated with blood and microbiological tests, in particular blood culture and swab. The laboratory, microbiologic or radiologic tests could be more or less detailed and targeted depending on the type of suspected infection and clinical conditions of the patient. When therapy is necessary, it is crucial to switch, as soon as possible, from broad spectrum antibiotic therapy to antibiotic therapy based on the results of the microbiological exams. Antibiotic therapy could be associated with antipyretic and specific organ support therapy when necessary.

Appropriateness of Dyslipidemia Management Strategies in Post-Acute Coronary Syndrome: A 2023 Update.

It has been consistently demonstrated that circulating lipids and particularly low-density lipoprotein cholesterol (LDL-C) play a significant role in the development of coronary artery disease (CAD). Several trials have been focused on the reduction of LDL-C values in order to interfere with atherothrombotic progression. Importantly, for patients who experience acute coronary syndrome (ACS), there is a 20% likelihood of cardiovascular (CV) event recurrence within the two years following the index event. Moreover, the mortality within five years remains considerable, ranging between 19 and 22%. According to the latest guidelines, one of the main goals to achieve in ACS is an early improvement of the lipid profile. The evidence-based lipid pharmacological strategy after ACS has recently been enhanced. Although novel lipid-lowering drugs have different targets, the result is always the overexpression of LDL receptors (LDL-R), increased uptake of LDL-C, and lower LDL-C plasmatic levels. Statins, ezetimibe, and PCSK9 inhibitors have been shown to be safe and effective in the post-ACS setting, providing a consistent decrease in ischemic event recurrence. However, these drugs remain largely underprescribed, and the consistent discrepancy between real-world data and guideline recommendations in terms of achieved LDL-C levels represents a leading issue in secondary prevention. Although the cost-effectiveness of these new therapeutic advancements has been clearly demonstrated, many concerns about the cost of some newer agents continue to limit their use, affecting the outcome of patients who experienced ACS. In spite of the fact that according to the current recommendations, a stepwise lipid-lowering approach should be adopted, several more recent data suggest a "strike early and strike strong" strategy, based on the immediate use of statins and, eventually, a dual lipid-lowering therapy, reducing as much as possible the changes in lipid-lowering drugs after ACS. This review aims to discuss the possible lipid-lowering strategies in post-ACS and to identify those patients who might benefit most from more powerful treatments and up-to-date management.

[The gender gap in cardiology (does it still exist?)]. / (Esiste ancora) il "gender gap" in cardiologia (?).

Gender gap is the gap between males and females related to gender. Several studies demonstrate that it has not been overcome yet, and it appears evident in differences in career chances due to gender. Such a gap is evident in the health system, particularly in cardiology. In the present review, gender gap in cardiology is addressed, considering different subspecialties, consequences in terms of career, and economic issues, causes of these inequalities, and cultural changes that might contribute to reduce gender gap.

[ANMCO Position paper: Choosing Wisely - ANMCO proposals for 2023]. / Position paper ANMCO: Choosing Wisely ­ le proposte dell'ANMCO nel 2023.

Nowadays, a progressive and exponential increase in the use of invasive and non-invasive instrumental diagnostics and therapeutic services has been shown. Although unnecessary, instrumental examinations are often largely prescribed, replacing clinical evaluation. Their correct use, on the contrary, would address precise epidemiological and clinical contexts. Therefore identifying whether a test or procedure is appropriate or not plays a crucial role in clinical practice. Several documents from scientific societies and expert groups indicate the most appropriate cardiovascular diagnostic and therapeutic procedures. The international Choosing Wisely campaign invited the main scientific societies to identify five techniques or treatments used in their field that are often unnecessary and may potentially damage patients. The Italian Association of Hospital Cardiologists (ANMCO) joined the project identifying the five cardiological practices in our country at greater risk of inappropriateness in 2014. This list has recently been updated. Moreover, possible solutions to this problem have been proposed.

Management of oral anticoagulant therapy after intracranial hemorrhage in patients with atrial fibrillation.

Intracranial hemorrhage (ICH) is considered a potentially severe complication of oral anticoagulants (OACs) and antiplatelet therapy (APT). Patients with atrial fibrillation (AF) who survived ICH present both an increased ischemic and bleeding risk. Due to its lethality, initiating or reinitiating OACs in ICH survivors with AF is challenging. Since ICH recurrence may be life-threatening, patients who experience an ICH are often not treated with OACs, and thus remain at a higher risk of thromboembolic events. It is worthy of mention that subjects with a recent ICH and AF have been scarcely enrolled in randomized controlled trials (RCTs) on ischemic stroke risk management in AF. Nevertheless, in observational studies, stroke incidence and mortality of patients with AF who survived ICH had been shown to be significantly reduced among those treated with OACs. However, the risk of hemorrhagic events, including recurrent ICH, was not necessarily increased, especially in patients with post-traumatic ICH. The optimal timing of anticoagulation initiation or restarting after an ICH in AF patients is also largely debated. Finally, the left atrial appendage occlusion option should be evaluated in AF patients with a very high risk of recurrent ICH. Overall, an interdisciplinary unit consisting of cardiologists, neurologists, neuroradiologists, neurosurgeons, patients, and their families should be involved in management decisions. According to available evidence, this review outlines the most appropriate anticoagulation strategies after an ICH that should be adopted to treat this neglected subset of patients.

The role of the pregnancy heart team in clinical practice.

Significant maternal and fetal morbidity and mortality risk has been shown to be associated with cardiovascular disease in pregnancy. Several determinants, such as the increasing number of females with corrected congenital heart disease in reproductive age, a more advanced maternal age associated with cardiovascular risk factors, and a greater prevalence of preexisting comorbidities related to cardiac disorders such as cancer and COVID-19), lead to a higher incidence of cardiac complications in pregnancy in the last few decades. However, adopting a multidisciplinary strategy may influence maternal and neonatal outcomes. This review aims at assessing the role of the Pregnancy Heart Team, which should ensure careful pre-pregnancy counseling, pregnancy monitoring, and delivery planning for both congenital and other cardiac or metabolic disorders, addressing several emerging aspects in the multidisciplinary team-based approach.

The r'-Wave Algorithm: A New Diagnostic Tool to Predict the Diagnosis of Brugada Syndrome after a Sodium Channel Blocker Provocation Test.

A diagnosis of Brugada syndrome (BrS) is based on the presence of a type 1 electrocardiogram (ECG) pattern, either spontaneously or after a Sodium Channel Blocker Provocation Test (SCBPT). Several ECG criteria have been evaluated as predictors of a positive SCBPT, such as the ß-angle, the α-angle, the duration of the base of the triangle at 5 mm from the r'-wave (DBT- 5 mm), the duration of the base of the triangle at the isoelectric line (DBT- iso), and the triangle base/height ratio. The aim of our study was to test all previously proposed ECG criteria in a large cohort study and to evaluate an r'-wave algorithm for predicting a BrS diagnosis after an SCBPT. We enrolled all patients who consecutively underwent SCBPT using flecainide from January 2010 to December 2015 in the test cohort and from January 2016 to December 2021 in the validation cohort. We included the ECG criteria with the best diagnostic accuracy in relation to the test cohort in the development of the r'-wave algorithm (ß-angle, α-angle, DBT- 5 mm, and DBT- iso.) Of the total of 395 patients enrolled, 72.4% were male and the average age was 44.7 ± 13.5 years. Following the SCBPTs, 24.1% of patients (n = 95) were positive and 75.9% (n = 300) were negative. ROC analysis of the validation cohort showed that the AUC of the r'-wave algorithm (AUC: 0.92; CI 0.85-0.99) was significantly better than the AUC of the ß-angle (AUC: 0.82; 95% CI 0.71-0.92), the α-angle (AUC: 0.77; 95% CI 0.66-0.90), the DBT- 5 mm (AUC: 0.75; 95% CI 0.64-0.87), the DBT- iso (AUC: 0.79; 95% CI 0.67-0.91), and the triangle base/height (AUC: 0.61; 95% CI 0.48-0.75) (p < 0.001), making it the best predictor of a BrS diagnosis after an SCBPT. The r'-wave algorithm with a cut-off value of ≥2 showed a sensitivity of 90% and a specificity of 83%. In our study, the r'-wave algorithm was proved to have the best diagnostic accuracy, compared with single electrocardiographic criteria, in predicting the diagnosis of BrS after provocative testing with flecainide.

Acute coronary syndrome in very elderly patients-a real-world experience.

Very elderly population constitutes an increasingly larger proportion of patients admitted for acute coronary syndromes (ACS). Notably, age represents both a proxy of frailty and an exclusion criterion in clinical randomized trials, which probably contributes to lack of data and undertreatment of real-world elderly patients. The aim of the study is to describe patterns of treatment and outcome of very elderly patients with ACS. All consecutive patients aged ≥ 80 years old (yo) admitted between January 2017 and December 2019 with ACS were included. The primary endpoint was in-hospital occurrence of major adverse cardiovascular events (MACE), defined as the composite of cardiovascular death, new onset cardiogenic shock, definite/probable stent thrombosis, and ischemic stroke. The secondary endpoints were in-hospital incidence of Thrombolysis in Myocardial Infarction (TIMI) major/minor bleedings, contrast-induced nephropathy (CIN), six-month all-cause mortality, and unplanned readmission. One hundred ninety-three patients (mean age 84.1 ± 3.5 yo, 46% females) were included, of whom 86 (44.6%), 79 (40.9%), and 28 (14.5%) presented with ST elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina (UA), respectively. The vast majority of patients received an invasive strategy, with 92.7% undergoing coronary angiography and 84.4% to percutaneous coronary intervention (PCI). Aspirin was administered to 180 (93.3%) patients, clopidogrel to 89 (46.1%) patients, and ticagrelor to 85 (44%) patients. In-hospital MACE occurred in 29 patients (15.0%), whereas 3 (1.6%) and 12 patients (7.2%) experienced in-hospital TIMI major and TIMI minor bleeding, respectively. Of the overall population, 177 (91.7%) were discharged alive. After discharge, 11 patients (6.2%) died of all-cause death, whereas 42 patients (23.7%) required a new hospitalization within six months. Invasive strategy of ACS in elderly patients seems safe and effective. Six-month new hospitalization appears inevitably related to age.

[Gaps in evidence in recent cardiovascular guidelines: uncertainties in chronic coronary syndrome]. / "Gaps in evidence" nelle recenti linee guida cardiovascolari: incertezze nella sindrome coronarica cronica.

The clinical guidelines, while representing an objective reference to perform correct therapeutic choices, contain grey zones, where the recommendations are not supported by solid evidence. In the fifth National Congress Grey Zones held in Bergamo in June 2022, an attempt was made to highlight some of the main grey zones in Cardiology and, through a comparison between experts, to draw shared conclusions that can illuminate our clinical practice. This manuscript contains the statements of the symposium concerning the controversies regarding ischemic cardiomyopathy. The manuscript represents the organization of the meeting, with an initial review of the current guidelines on this topic, followed by an expert presentation of pros (White) and cons (Black) related to the identified "gaps of evidence". For every issue is then reported the "response" derived from the votes of the experts and the public, the discussion and, finally, the highlights, which are intended as practical take home messages to be used in the everyday clinical practice. The first gap in evidence discussed regards the validity of the indication to search for ischemia in light of the data from the ISCHEMIA trial. The second examines the possibility of modifying the algorithm proposed by the European guidelines on anti-ischemic therapy in chronic coronary syndromes. The last gap in evidence evaluates the comparability of long-term antithrombotic strategies in chronic coronary syndromes.

[Circulatory shock: early diagnosis and therapy]. / Shock circolatorio: diagnosi e terapia precoce.

Circulatory shock is a clinical condition characterized by hypotension and organ hypoperfusion, potentially fatal if the underlying cause is not promptly identified and corrected. Circulatory shock outcome is certainly conditioned from early diagnosis and early and adequate therapy. The aim of this review is to provide a tool for a rapid differential diagnosis among the various phenotypes of circulatory shock, based on the clinical, hemodynamic and biochemical profile. We also prompt to emphasize the role of multiparametric monitoring from the early phases of the management and the need to implement the time-dependent network to improve the outcome of these critical patients.

Safety and feasibility of angiotensin receptor neprilysin inhibitor in real-world patients with acute decompensated heart failure.

BACKGROUND: The aim of this study was to determine the safety and feasibility of in-hospital sacubitril/valsartan initiation after clinical stabilization in patients with acute decompensated heart failure (ADHF) and reduced ejection fraction (EF). METHODS: This retrospective, multicenter observational study included patients admitted for ADHF in 2 Italian centers between February 2017 and January 2022. Feasibility was evaluated by assessing the proportion of patients discharged on sacubitril/valsartan. Key safety endpoints were the incidences of adverse events during hospitalization and during follow-up planned at 1 month, 3-6 months and 12-18 months after discharge. RESULTS: One hundred and twenty-two patients were included. Median age was 71 (60-78) years, 78% male, 63% New York Heart Association (NYHA) Class III at admission with a median left ventricular ejection fraction (EF) of 25% (20-30). During hospitalization, 94 (77%) patients were treated with intravenous diuretics, 39 (32%) with inotrope/vasopressor, 51 (42%) with continuous positive airway pressure ventilation and 7 (6%) were assisted with an intra-aortic balloon pump. Median time from hospitalization to sacubitril/valsartan initiation was 4 (2-7) days. Sacubitril/valsartan was started at a dosage of 12/13 mg in 52 (43%) patients, 24/26 mg in 61 (50%) patients and 49/51 mg in 8 (7%) patients. Overall, 111 (91%) patients were discharged on sacubitril/valsartan. At 12-18-month follow-up, the vast majority of patients were still on sacubitril/valsartan therapy. CONCLUSIONS: In-hospital initiation of sacubitril/valsartan treatment in real-world ADHF patients may be a safe and feasible treatment option.

A case of shock after STEMI: Think beyond the cardiogenic one.

Acute ST-segment elevation myocardial infarction (STEMI) can typically complicate with the development of cardiogenic shock; nevertheless, other less frequent types of shock may occur, including adrenal crisis (AC). We describe a case of STEMI complicated by AC and, for the first time, AC-induced focal takotsubo syndrome.