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.

Coagulation Tests and Reversal Agents in Patients Treated with Oral Anticoagulants: The Challenging Scenarios of Life-Threatening Bleeding and Unplanned Invasive Procedures.

In clinical practice, the number of patients treated with direct oral anticoagulants (DOACs) has consistently increased over the years. Since anticoagulant therapy has been associated with an annual incidence of major bleeding (MB) events of approximately 2% to 3.5%, it is of paramount importance to understand how to manage anticoagulated patients with major or life-threatening bleeding. A considerable number of these patients' conditions necessitate hospitalization, and the administration of reversal agents may be imperative to manage and control bleeding episodes effectively. Importantly, effective strategies for reversing the anticoagulant effects of DOACs have been well recognized. Specifically, idarucizumab has obtained regulatory approval for the reversal of dabigatran, and andexanet alfa has recently been approved for reversing the effects of apixaban or rivaroxaban in patients experiencing life-threatening or uncontrolled bleeding events. Moreover, continuous endeavors are being made to develop supplementary reversal agents. In emergency scenarios where specific reversal agents might not be accessible, non-specific hemostatic agents such as prothrombin complex concentrate can be utilized to neutralize the anticoagulant effects of DOACs. However, it is paramount to emphasize that specific reversal agents, characterized by their efficacy and safety, should be the preferred choice when suitable. Moreover, it is worth noting that adherence to the guidelines for the reversal agents is poor, and there is a notable gap between international recommendations and actual clinical practices in this regard. This narrative review aims to provide physicians with a practical approach to managing specific reversal agents.

Heart Failure with Preserved Ejection Fraction: How to Deal with This Chameleon.

Heart failure with preserved ejection fraction (HFpEF) is characterized by a notable heterogeneity in both phenotypic and pathophysiological features, with a growing incidence due to the increase in median age and comorbidities such as obesity, arterial hypertension, and cardiometabolic disease. In recent decades, the development of new pharmacological and non-pharmacological options has significantly impacted outcomes, improving clinical status and reducing mortality. Moreover, a more personalized and accurate therapeutic management has been demonstrated to enhance the quality of life, diminish hospitalizations, and improve overall survival. Therefore, assessing the peculiarities of patients with HFpEF is crucial in order to obtain a better understanding of this disorder. Importantly, comorbidities have been shown to influence symptoms and prognosis, and, consequently, they should be carefully addressed. In this sense, it is mandatory to join forces with a multidisciplinary team in order to achieve high-quality care. However, HFpEF remains largely under-recognized and under-treated in clinical practice, and the diagnostic and therapeutic management of these patients remains challenging. The aim of this paper is to articulate a pragmatic approach for patients with HFpEF focusing on the etiology, diagnosis, and treatment of HFpEF.

Impact of Contrast-Associated Acute Kidney Injury on One-Year Outcomes in Very Elderly STEMI Patients: Insights From a Multicenter Registry in Northern Italy.

Data about contrast-associated acute kidney injury (CA-AKI) in oldest old (age ≥85 years) ST-elevation myocardial infarction (STEMI) patients are scarce. We evaluated the incidence and the 1-year prognostic impact of CA-AKI in this population. Patients were included in a multicenter real-world registry, and CA-AKI was defined according to KDIGO (Kidney Disease Improving Global Outcomes) criteria. Major adverse cardiac and cerebrovascular events (MACCEs) were defined as the composite of all-cause death, stroke, unplanned coronary revascularization, and heart failure hospitalization. The primary outcome was the incidence and impact of CA-AKI on MACCEs at 1 year follow-up. Out of 461 STEMI patients (mean age 88.6 ± 2.9 years), 102 (22.1%) patients developed CA-AKI. Chronic kidney disease was the strongest predictor of CA-AKI (odds ratio [OR]: 4.52, 95% CI: 2.81-7.30, P < .01). The CA-AKI cohort showed a higher risk of MACCEs (adjusted HR: 1.75, 95% CI: 1.13-2.71, P = .01), driven mainly by all-cause death (adjusted hazard ratio [HR]: 2.39, 95% CI: 1.41-4.07, P = .01) and followed by heart failure hospitalization (adjusted HR: 2.01, 95% CI: 1.08-3.76, P = .01). Among oldest old STEMI, CA-AKI was frequent and associated with a higher incidence of MACCEs at 1-year follow-up.

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.

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

It is well established that gender strongly influences cardiovascular risk factors, playing a crucial role in cardiovascular prevention, clinical pathways, diagnostic approach and treatment. Beyond the sex, which is a biological factor, gender entails a socio-cultural condition that impacts access and quality of care due to structural and institutional barriers. However, despite its great importance, this issue has not been adequately covered. Indeed sex and gender differences scarcely impact the clinical approach, creating a lot of disparities in care and outcomes of patients. Therefore, it becomes essential to increase the awareness of the importance of sex and gender influences on cardiovascular diseases. Moreover, new strategies for reducing disparities should be developed. Importantly, these differences should be taken into account in guideline recommendations. In this regard, it is crucial to include a greater number of women in clinical trials, since they are currently underrepresented. Furthermore, more women should be involved as member of international boards in order to develop recommendations and guidelines with more attention to this important topic.The aim of this ANMCO position paper is to shed light on gender differences concerning many cardiovascular drugs in order to encourage a more personalized therapeutic approach.

[ANMCO Position paper: 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 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.

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.

Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction.

BACKGROUND: The benefit of complete revascularization in older patients (≥75 years of age) with myocardial infarction and multivessel disease remains unclear. METHODS: In this multicenter, randomized trial, we assigned older patients with myocardial infarction and multivessel disease who were undergoing percutaneous coronary intervention (PCI) of the culprit lesion to receive either physiology-guided complete revascularization of nonculprit lesions or to receive no further revascularization. Functionally significant nonculprit lesions were identified either by pressure wire or angiography. The primary outcome was a composite of death, myocardial infarction, stroke, or any revascularization at 1 year. The key secondary outcome was a composite of cardiovascular death or myocardial infarction. Safety was assessed as a composite of contrast-associated acute kidney injury, stroke, or bleeding. RESULTS: A total of 1445 patients underwent randomization (720 to receive complete revascularization and 725 to receive culprit-only revascularization). The median age of the patients was 80 years (interquartile range, 77 to 84); 528 patients (36.5%) were women, and 509 (35.2%) were admitted for ST-segment elevation myocardial infarction. A primary-outcome event occurred in 113 patients (15.7%) in the complete-revascularization group and in 152 patients (21.0%) in the culprit-only group (hazard ratio, 0.73; 95% confidence interval [CI], 0.57 to 0.93; P = 0.01). Cardiovascular death or myocardial infarction occurred in 64 patients (8.9%) in the complete-revascularization group and in 98 patients (13.5%) in the culprit-only group (hazard ratio, 0.64; 95% CI, 0.47 to 0.88). The safety outcome did not appear to differ between the groups (22.5% vs. 20.4%; P = 0.37). CONCLUSIONS: Among patients who were 75 years of age or older with myocardial infarction and multivessel disease, those who underwent physiology-guided complete revascularization had a lower risk of a composite of death, myocardial infarction, stroke, or ischemia-driven revascularization at 1 year than those who received culprit-lesion-only PCI. (Funded by Consorzio Futuro in Ricerca and others; FIRE ClinicalTrials.gov number, NCT03772743.).

[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.

A Tailored Antithrombotic Approach for Patients with Atrial Fibrillation Presenting with Acute Coronary Syndrome and/or Undergoing PCI: A Case Series.

The combination of oral anticoagulants (OAC) and dual antiplatelet therapy (DAPT) is the mainstay for the treatment of patients with atrial fibrillation (AF) presenting with acute coronary syndrome (ACS) and/or undergoing PCI. However, this treatment leads to a significant increase in risk of bleeding. In most cases, according to the most recent guidelines, triple antithrombotic therapy (TAT) consisting of OAC and DAPT, typically aspirin and clopidogrel, should be limited to one week after ACS and/or PCI (default strategy). On the other hand, in patients with a high ischemic risk (i.e., stent thrombosis) and without increased risk of bleeding, TAT should be continued for up to one month. Direct oral anticoagulants (DOAC) in triple or dual antithrombotic therapy (OAC and P2Y12 inhibitor) should be favored over vitamin K antagonists (VKA) because of their favorable risk/benefit profile. The choice of the duration of TAT (one week or one month) depends on a case-by-case evaluation of a whole series of hemorrhagic or ischemic risk factors for each patient. Likewise, the specific DOAC treatment should be selected according to the clinical characteristics of each patient. We propose a series of paradigmatic clinical cases to illustrate the decision-making work-up in clinical practice.

Transcatheter aortic valve intervention in hospitals without cardiac surgery departments: a future scenario?

Transcatheter Aortic Valve Intervention (TAVI) was introduced in early 2000 to offer treatment to inoperable patients with severe aortic valve stenosis. In a couple of decades, the procedure resulted effective and safe also in patients with intermediate to low risk for surgery; therefore, due to the progressive ageing of the population, the clinical need for TAVI is continuously increasing and is hardly met by the availability of the procedure, the so-called "TAVI capacity". As a result, many patients encounter difficulties in being referred to TAVI centers or face long waiting list times, thus risking severe adverse events (including death) before the procedure is performed. Although contemporary guidelines and consensus documents recommend that TAVI should be only performed in hospitals with active cardiac surgery departments, starting TAVI programs also in interventional cardiac laboratories without on-site cardiac surgery could represent a way to increase TAVI capacity, thus leading to a greater number of patients being treated in less time. On the other side of the coin, such a strategy may jeopardize patient safety in case of periprocedural complications needing bailout surgery and may lead to a suboptimal multidisciplinary Heart Team evaluation. This review aims to assess and discuss available clinical data and implementation of TAVI programs in hospitals without on-site active cardiac surgery departments considering the growing unmet clinical need and technical advancement of TAVI platforms, yet not overlooking the recommendation of international scientific societies.

Fractional flow reserve in patients with type 1 or type 2 non-ST elevation acute myocardial infarction.

AIMS: We assessed a combined strategy of fractional flow reserve (FFR) plus angiography in stratifying cardiovascular risk in patients with type 1 myocardial infarction (T1MI) or type 2 (T2MI) non-ST elevation acute myocardial infarction (NSTEMI). METHODS: A cohort of 150 NSTEMI patients were prospectively studied. Clinical and angiographic features guided the identification of T1MI vs T2MI and the treatment of culprit lesions. Subsequently, T1MI patients underwent FFR evaluation of nonculprit stenoses. In T2MI patients all angiographically significant stenoses were evaluated by FFR. FFR < 0.80 was an indication for revascularization. Based on FFR results, two groups were compared: patients with all lesions ≥0.80 ('defer' group, n = 87) and those with at least one lesion <0.80 ('perform' group, n = 63). The primary end point was the composite of all-cause death, nonfatal MI and unplanned coronary revascularization. RESULTS: Median clinical follow-up was of 35 months (interquartile range 14-44). Primary end-point rates in the 'defer' and 'perform' groups were 14.5% and 30.0% at 12 months and 28% and 46% at 36 months, respectively (log-rank test: at 1 year, P = 0.007; at the end of follow-up P = 0.014). On multivariable analysis, chronic kidney disease (HR 3.50, 95% CI: 1.89-6.46, P = 0.0001) and FFR group ('perform' vs 'defer': HR 1.75 95% CI: 1.01-3.04, P = 0.046) were independent predictors of adverse events. CONCLUSIONS: In NSTEMI patients, our results indicated that FFR combined with angiography allowed the treatment of nonfunctional significant lesions to be safely deferred and patient cardiovascular risk to be identified.

Clinical characteristics, management and outcomes of patients with acute coronary syndrome and atrial fibrillation: real-world data from two nationwide registries in Italy.

BACKGROUND: Atrial fibrillation is common in the setting of acute coronary syndromes (ACS) although its impact on ACS remains controversial. AIM: To describe in-hospital management of patients with atrial fibrillation and ACS evaluating the impact of atrial fibrillation on in-hospital and mid-term outcome. METHODS: We analysed the data of two prospective multicentre nationwide registries (IN-ACS Outcome and MANTRA) to assess clinical characteristics, management, and outcomes of patients with ACS and atrial fibrillation. Study outcomes included death from any cause and a composite end-point of death/re-infarction/stroke/major bleeding within index admission and 6 months' follow-up. RESULTS: Out of 12 288 ACS patients, 1236 (10.1%) had atrial fibrillation at admission or developed it during hospitalization. Atrial fibrillation patients were older, more often female, and had higher burden of comorbidities. In-hospital mortality was higher among atrial fibrillation patients (8.7 vs. 2.4%, P < 0.001). Patients with atrial fibrillation had a higher incidence of re-infarction (3.5 vs. 1.7%, P < 0.0001) and ischemic stroke (1.7 vs. 0.4%, P < 0.001) compared with those in sinus rhythm. Major bleedings were also more frequent among atrial fibrillation patients (1.9 vs. 0.9%, P < 0.001). In-hospital and at 6 months' follow-up death from any cause occurred more often in atrial fibrillation patients than in those without atrial fibrillation (9.4 vs. 3.5%, P < 0.0001). At multivariable analysis, atrial fibrillation was an independent predictor of the in-hospital composite end-point (OR 1.67, 95% CI 1.35-2.06, P < 0.0001) but not at 6 months' follow-up. The independent role of atrial fibrillation on the in-hospital composite end-point was also confirmed by propensity score analyses. CONCLUSION: Atrial fibrillation was an independent predictor for adverse in-hospital outcome in ACS. This effect disappeared at mid-term follow-up, whereas noncardiac comorbidities emerged as prognostic factors of adverse outcomes.

Acute coronary syndromes with high thrombotic burden: therapeutic innovations.

Antiplatelet agents represent one of the cornerstones of drug therapy for acute coronary syndromes (ACS). In the last decade, the arrival of prasugrel and ticagrelor, faster and more powerful oral platelet receptor P2Y12 inhibitors compared to clopidogrel, significantly improved platelet inhibition in patients with ACS. However, the reduction of thrombotic risk came at the cost of increased bleeding risk. Despite having similar indications, prasugrel and ticagrelor have different characteristics and methods of use, essentially due to a different design of the trials in which they have been studied. The optimal use of these antiplatelets in clinical practice should therefore be tailored in individual patients. In the acute phase of ACS with high thrombotic burden, all oral P2Y12 inhibitors have limitations, mainly due to the delay of onset of action related to oral administration. In this scenario, parenteral antiplatelet agents (glycoprotein inhibitors IIb/IIIa and cangrelor) may play a key role in case of percutaneous coronary interventions of high thrombotic coronary lesions and in the prevention of early thrombotic complications. Cangrelor, an intravenous inhibitor of the P2Y2 receptor, has peculiar pharmacokinetic and pharmacodynamic characteristics that make it particularly suitable to be used as an antiplatelet during coronary angioplasty as it achieves a rapid and powerful antiplatelet effect in patients not pretreated with oral medications, and has a favourable safety profile in relation to the bleeding risk.

A handbook for the clinical cardiologist about CRT/ICD. A practical guide about how to survive during an on call shift.

Cardiac resynchronization therapies (CRTs) have been demonstrated to improve the clinical management and prognosis of selected patients with heart failure. CRT devices include both CRT pacemakers (CRT-P) and CRT defibrillators (CRT-D), with the latter being used to treat life-threatening ventricular arrhythmias. A significant advantage of CRTs is the ability to monitor several vital parameters which, thanks to advanced technology, may be remotely assessed. Personalized programming options allow patients to receive the maximum benefit from these treatments. In this review we report the main diagnostic and therapeutic algorithms used in clinical practice.