Antithrombotic Therapy in High Bleeding Risk, Part I: Percutaneous Cardiac Interventions.

Antithrombotic therapy after cardiac percutaneous interventions is key for the prevention of thrombotic events but is inevitably associated with increased bleeding, proportional to the number, duration, and potency of the antithrombotic agents used. Bleeding complications have important clinical implications, which in some cases may outweigh the expected benefit of reducing thrombotic events. Because the response to antithrombotic agents varies widely among patients, there has been a relentless effort toward the identification of patients at high bleeding risk (HBR), in whom modulation of antithrombotic therapy may be needed to optimize the balance between safety and efficacy. Among patients undergoing cardiac percutaneous interventions, recent advances in technology have allowed for strategies of de-escalation to reduce bleeding without compromising efficacy, and HBR patients are expected to benefit the most from such approaches. Guidelines do not extensively expand upon the topic of de-escalation strategies of antithrombotic therapy in HBR patients. In this review, we discuss the evidence and provide practical recommendations on optimal antithrombotic therapy in HBR patients undergoing various cardiac percutaneous interventions.

Cardiovascular disease and psychiatric disorders: An-up-to date review.

Cardiovascular diseases (CVD) and mental health disorders (MHD) are respectively the first and second most prevalent diseases in high-income countries and the two most relevant causes of disability worldwide. The close association between the two conditions has been known for a long time and research has been able to document how the co-morbidity between cardiovascular disorders and mental health disorders is a negative prognostic factor for both conditions. This strong connection and the relevance of the impact of the association have led to define a new branch of cardiology, known as behavioral cardiology. The aim of the new branch is just to study the nexus CVD-MHD in order to prevent or decrease the burden of MHD on CVD and vice versa. This review describes the epidemiological evidence of the relationship between MHD on CVD at the state of the art among clinical research.

Italian Cardiological Guidelines (COCIS) for Competitive Sport Eligibility in athletes with heart disease: update 2024.

Nearly 35 years after its initial publication in 1989, the Italian Society of Sports Cardiology and the Italian Federation of Sports Medicine (FMSI), in collaboration with other leading Italian Cardiological Scientific Associations (ANCE - National Association of Outpatient Cardiology, ANMCO - National Association of Inpatient Cardiology, SIC - Italian Society of Cardiology), proudly present the 2023 version of the Cardiological Guidelines for Competitive Sports Eligibility. This publication is an update of the previous guidelines, offering a comprehensive and detailed guide for the participation of athletes with heart disease in sports. This edition incorporates the latest advances in cardiology and sports medicine, providing current information and recommendations. It addresses various topics, including the details of the pre-participation screening in Italy and recommendations for sports eligibility and disqualification in competitive athletes with various heart conditions. This revised version of the Cardiological Guidelines for Competitive Sports Eligibility, recorded in the Italian Guidelines Registry of the Italian Minister of Health, stands as a crucial resource for sports medicine professionals, cardiologists, and healthcare providers, marked by its completeness, reliability, and scientific thoroughness. It is an indispensable tool for those involved in the care, management and eligibility process of competitive athletes with heart conditions.

Antithrombotic Therapy in High Bleeding Risk, Part II: Noncardiac Percutaneous Interventions.

Over the past decades, there have been great advancements in the antithrombotic management of patients undergoing percutaneous interventions, but most of the available evidence derives from studies conducted in the setting of cardiac interventions. Antithrombotic treatment regimens used in patients undergoing percutaneous cardiac interventions, in particular coronary, are frequently extrapolated to patients undergoing noncardiac interventions. However, the differences in risk profile of the population treated and the types of interventions performed may translate into differences is the safety and efficacy associated with antithrombotic therapy. Noncardiac percutaneous interventions are commonly performed in patients at high bleeding risk, which may indeed impact outcomes, hence underscoring the importance of risk stratification to guide clinical decision-making processes. In this review, we appraise the available evidence on antithrombotic therapy in high-bleeding-risk patients undergoing noncardiac percutaneous interventions.

Feasibility of a Cardiac Magnetic Resonance Protocol for "off-on" Cardiac Resynchronization Therapy Evaluation.

BACKGROUND: Cardiac resynchronization therapy (CRT) is a standard treatment for patients with heart failure and electrical dyssynchrony. Cardiac magnetic resonance (CMR) is the gold standard for assessing left ventricular (LV) function. However, the feasibility of using CMR with active CRT is still uncertain. PURPOSE: To assess the feasibility of a CRT "off-on" protocol during CMR and measure the acute effects of CRT interruption on LV function. METHODS: Patients underwent CMR before (pre-CRT) and 6 months after (post-CRT) an MR-conditional CRT defibrillator implantation. The post-CRT scan included two complete sets of cine images, one with inactive (post-CRTOFF) and one with active CRT (post-CRTON), maintaining a continuous connection between device and programmer. RESULTS: Out of 29 enrolled patients, 8 (28%) had complete and analyzable post-CRT data. Unsuccessful procedures were attributed to connection problems between the CRT device and the programmer (n = 10), poor image quality (n = 7), and lack of patient cooperation (n = 4). LV ejection fraction significantly increased between pre-CRT scan (28.1%) and both post-CRTOFF (37.9%; p = 0.046) and post-CRTON CMR (35.0%; p = 0.037), with a nonstatistically significant trend toward decreased LV volumes. No adverse events or significant changes in device electrical parameters (including battery level) were detected during the post-CMR scan period. CONCLUSION: A CRT "off-on" protocol during CMR studies can be safely executed in patients with an MR-conditional CRT defibrillator. However, technical improvements are needed to facilitate high-quality scans during active CRT. Favorable changes in LV function induced by CRT remodeling were not acutely reversed with the interruption of electrical therapy.

[Hypercholesterolemia and laboratory reports: joint document from the Italian Society of Cardiology (SIC) and the Italian Society of Clinical Biochemistry and Clinical Molecular Biology - Lab Medicine (SIBioC)]. / Ipercolesterolemia e referti di laboratorio: documento congiunto della Società Italiana di Cardiologia (SIC) e Società Italiana di Biochimica Clinica e Biologia Molecolare Clinica - Medicina di Laboratorio (SIBioC).

Dyslipidemia is one of the most important risk factors for the development of atherosclerotic disease and its control, through well-proven therapies, allows an optimal risk management over time. LDL-cholesterol targets are well defined by international guidelines and based on individual cardiovascular risk. As guidelines evolve, also laboratory reports need to do the same, including lipid reference values by cardiovascular risk classes, to avoid misunderstandings and inappropriate lipid-lowering therapy withdrawal. The aim of the present joint document from the Italian Society of Cardiology (SIC) and the Italian Society of Clinical Biochemistry and Clinical Molecular Biology - Lab Medicine (SIBioC) is to analyze the importance of cardiovascular risk estimation, therapeutical targets, and crucial elements about dyslipidemia in laboratory tests, as well as to suggest a shared proposal for the report of lipid profile parameters to be applied to all clinical scenarios of our daily practice.

Optimizing Management of Stable Angina: A Patient-Centered Approach Integrating Revascularization, Medical Therapy, and Lifestyle Interventions.

Angina pectoris may arise from obstructive coronary artery disease (CAD) or in the absence of significant CAD (ischemia with nonobstructed coronary arteries [INOCA]). Therapeutic strategies for patients with angina and obstructive CAD focus on reducing cardiovascular events and relieving symptoms, whereas in INOCA the focus shifts toward managing functional alterations of the coronary circulation. In obstructive CAD, coronary revascularization might improve angina status, although a significant percentage of patients present angina persistence or recurrence, suggesting the presence of functional mechanisms along with epicardial CAD. In patients with INOCA, performing a precise endotype diagnosis is crucial to allow a tailored therapy targeted toward the specific pathogenic mechanism. In this expert opinion paper, we review the evidence for the management of angina, highlighting the complementary role of coronary revascularization, optimal medical therapy, and lifestyle interventions and underscoring the importance of a personalized approach that targets the underlying pathobiology.

Maternal-fetal dyad beyond the phenomenology of pregnancy: from primordial cardiovascular prevention on out, do not miss this boat!

Pregnancy represents a stress test for every woman's cardiovascular (CV) system, and a pre-existing maternal unfavorable cardio-metabolic phenotype can uncover both adverse pregnancy outcomes and the subsequent development of cardiovascular disease (CVD) risk factors during and after pregnancy. Moreover, the maternal cardiac and extracardiac environment can affect offspring's cardiovascular health through a complex mechanism called developmental programming, in which fetal growth can be influenced by maternal conditions. This interaction continues later in life, as adverse developmental programming, along with lifestyle risk factors and genetic predisposition, can exacerbate and accelerate the development of CV risk factors and CVD in childhood and adolescence. The aim of this narrative review is to summarize the latest evidences regarding maternal-fetal dyad and its role on primordial, primary and secondary CV prevention.

Consensus document on diagnosis and management of familial hypercholesterolemia from the Italian Society for the Study of Atherosclerosis (SISA).

AIMS: Familial Hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism that causes an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Although early diagnosis and treatment of FH can significantly improve the cardiovascular prognosis, this disorder is underdiagnosed and undertreated. For these reasons the Italian Society for the Study of Atherosclerosis (SISA) assembled a Consensus Panel with the task to provide guidelines for FH diagnosis and treatment. DATA SYNTHESIS: Our guidelines include: i) an overview of the genetic complexity of FH and the role of candidate genes involved in LDL metabolism; ii) the prevalence of FH in the population; iii) the clinical criteria adopted for the diagnosis of FH; iv) the screening for ASCVD and the role of cardiovascular imaging techniques; v) the role of molecular diagnosis in establishing the genetic bases of the disorder; vi) the current therapeutic options in both heterozygous and homozygous FH. Treatment strategies and targets are currently based on low-density lipoprotein cholesterol (LDL-C) levels, as the prognosis of FH largely depends on the magnitude of LDL-C reduction achieved by lipid-lowering therapies. Statins with or without ezetimibe are the mainstay of treatment. Addition of novel medications like PCSK9 inhibitors, ANGPTL3 inhibitors or lomitapide in homozygous FH results in a further reduction of LDL-C levels. LDL apheresis is indicated in FH patients with inadequate response to cholesterol-lowering therapies. CONCLUSION: FH is a common, treatable genetic disorder and, although our understanding of this disease has improved, many challenges still remain with regard to its identification and management.

The Italian Fabry Disease Cardiovascular Registry (IFDCR).

AIMS: The Italian Fabry Disease Cardiovascular Registry (IFDCR) comprises 50 Italian centres with specific expertise in managing cardiovascular manifestations and complications of patients with Fabry disease (FD). The primary aim of the IFDCR is to examine and improve the clinical care and outcomes of patients with FD by addressing several knowledge gaps in the epidemiology, natural history, genotype-phenotype correlations, diagnosis, and management of this condition, with particular focus on cardiovascular manifestations and complications. METHODS AND RESULTS: The IFDCR is an international, longitudinal, multicentre, non-interventional, observational study. Consecutive patients aged ≥2 years with a diagnosis of FD will be included in the study. The recruitment period consists of two parts: the retrospective enrolment period, from January 1981 to December 2023, and the prospective enrolment period, spanning from January 2024 to December 2031. The registry collects baseline and follow-up data, including the enrolment setting, patient demographics, family history, symptoms, clinical manifestations, electrocardiogram, cardiovascular imaging, laboratory assessment, medical therapy, genetic testing results, and outcomes. CONCLUSIONS: The IFDCR is a national, multicentre, registry that includes patients with FD. It holds detailed and multiparametric data across the patient pathway and clinical manifestations, acting as a powerful tool for improving the quality of care and conducting high-impact research.

Subclinical hypothyroidism predicts outcome in heart failure: insights from the T.O.S.CA. registry.

Subclinical hypothyroidism (SH), defined as increased serum thyroid-stimulating hormone (TSH) with normal free T4 (fT4) levels, is frequently observed in the general population. Prevalence ranges from 0.6% to 1.8% in the adult population, depending on age, sex, and iodine intake. Several studies reported a worse prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and SH, but they considered heterogeneous populations suffering mainly from severe SH. Aim of this study was to evaluate if SH was independently associated with the occurrence of cardiovascular death considering 30 months of follow-up. 277 HFrEF patients enrolled in the prospective, multicenter, observational T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, were included in this analysis. Patients were divided into two groups according to the presence of SH (serum TSH levels > 4.5 mIU/L with normal fT4 levels). Data regarding clinical status, echocardiography, and survival were analyzed. Twenty-three patients displayed SH (87% mild vs 13% severe), while 254 were euthyroid. No differences were found in terms of age, sex, HF etiology, and left ventricular ejection fraction. When compared with the euthyroid group, SH patients showed higher TSH levels (7.7 ± 4.1 vs 1.6 ± 0.9, p < 0.001), as expected, with comparable levels of fT4 (1.3 ± 0.3 vs 1.3 ± 0.3, p = NS). When corrected for established predictors of poor outcome in HF, the presence of SH resulted to be an independent predictor of cardiovascular mortality (HR: 2.96; 5-95% CI:1.13-7.74; p = 0.03). Since thyroid tests are widely available and inexpensive, they should be performed in HF patients to detect subclinical disorders, evaluate replacement therapy, and improve prognosis.

The Role of Multimodality Imaging (CT & MR) as a Guide to the Management of Chronic Coronary Syndromes.

Chronic coronary syndrome (CCS) is one of the leading cardiovascular causes of morbidity, mortality, and use of medical resources. After the introduction by international guidelines of the same level of recommendation to non-invasive imaging techniques in CCS evaluation, a large debate arose about the dilemma of choosing anatomical (with coronary computed tomography angiography (CCTA)) or functional imaging (with stress echocardiography (SE), cardiovascular magnetic resonance (CMR), or nuclear imaging techniques) as a first diagnostic evaluation. The determinant role of the atherosclerotic burden in defining cardiovascular risk and prognosis more than myocardial inducible ischemia has progressively increased the use of a first anatomical evaluation with CCTA in a wide range of pre-test probability in CCS patients. Functional testing holds importance, both because the role of revascularization in symptomatic patients with proven ischemia is well defined and because functional imaging, particularly with stress cardiac magnetic resonance (s-CMR), gives further prognostic information regarding LV function, detection of myocardial viability, and tissue characterization. Emerging techniques such as stress computed tomography perfusion (s-CTP) and fractional flow reserve derived from CT (FFRCT), combining anatomical and functional evaluation, appear capable of addressing the need for a single non-invasive examination, especially in patients with high risk or previous revascularization. Furthermore, CCTA in peri-procedural planning is promising to acquire greater importance in the non-invasive planning and guiding of complex coronary revascularization procedures, both by defining the correct strategy of interventional procedure and by improving patient selection. This review explores the different roles of non-invasive imaging techniques in managing CCS patients, also providing insights into preoperative planning for percutaneous or surgical myocardial revascularization.

[SIC Position paper: Treat to prevent the first event - intensive LDL cholesterol lowering in patients at very high cardiovascular risk without a previous cardiovascular event. From ESC guidelines to clinical practice]. / Position paper SIC: Trattare per prevenire ­ la riduzione intensiva del colesterolo LDL nel paziente a rischio cardiovascolare molto alto senza pregresso evento. Dalle linee guida ESC alla pratica clinica.

Cardiovascular (CV) diseases account for over 4 million deaths every year in Europe and over 220 000 deaths in Italy, representing the leading cause of morbidity and mortality worldwide. The European Society of Cardiology (ESC) guidelines have visionary included in the at very high CV risk group patients without previous acute ischemic events, such as those with subclinical atherosclerosis, chronic coronary syndrome or peripheral arterial disease, familial hypercholesterolemia, diabetes mellitus with target organ damage or multiple associated risk factors, and those with high calculated CV risk score, recommending to consider them and to achieve the same LDL-cholesterol targets as for secondary prevention patients. The aim of this position paper is to provide an updated overview of ESC guidelines that focuses on these patient categories to raise awareness within the clinical community regarding CV risk reduction in this specific epidemiological context.

Physical exercise in hypertensive heart disease: From the differential diagnosis to the complementary role of exercise.

Arterial hypertension (AH) is one of the most common pathologic conditions and uncontrolled AH is a leading risk factor for cardiovascular disease and mortality. AH chronically causes myocardial and arterial remodelling with hemodynamic changes affecting the heart and other organs, with potentially irreversible consequences leading to poor outcomes. Therefore, a proper and early treatment of AH is crucial after the diagnosis. Beyond medical treatment, physical exercise also plays a therapeutic role in reducing blood pressure, given its potential effects on sympathetic tone, renin-angiotensin-aldosterone system, and endothelial function. International scientific societies recommend physical exercise among lifestyle modifications to treat AH in the first stages of the disease. Moreover, some studies have also shown its usefulness in addition to drugs to reduce blood pressure further. Therefore, an accurate, personalized exercise prescription is recommended to optimize the prevention and treatment of hypertension. On the other hand, uncontrolled AH in athletes requires proper risk stratification and careful evaluation to practice competitive sports safely. Moreover, the differential diagnosis between hypertensive heart disease and athlete's heart is sometimes challenging and requires a careful and comprehensive interpretation in order not to misinterpret the clinical findings. The present review aims to discuss the relationship between hypertensive heart disease and physical exercise, from diagnostic tools to prevention and treatment strategies.

OPTImal PHARMacological therapy for patients with heart failure: Rationale and design of the OPTIPHARM-HF registry.

AIMS: Patients with heart failure (HF) remain often undertreated for multiple reasons, including treatment inertia, contraindications, and intolerance. The OPTIimal PHARMacological therapy for patients with Heart Failure (OPTIPHARM-HF) registry is designed to evaluate the prevalence of evidence-based medical treatment prescription and titration, as well as the causes of its underuse, in a broad real-world population of consecutive patients with HF across the whole ejection fraction spectrum and among different clinical phenotypes. METHODS: The OPTIPHARM-HF registry (NCT06192524) is a prospective, multicenter, observational, national study of adult patients with symptomatic HF, as defined by current international guidelines, regardless of ejection fraction. Both outpatients and inpatients with chronic and acute decompensated HF will be recruited. The study will enroll up to 2500 patients with chronic HF at approximately 35 Italian HF centres. Patients will be followed for a maximum duration of 24 months. The primary objective of the OPTIPHARM-HF registry is to assess prescription and adherence to evidence-based guideline-directed medical therapy (GDMT) in patients with HF. The primary outcome is to describe the prevalence of GDMT use according to target guideline recommendation. Secondary objectives include implementation of comorbidity treatment, evaluation of sequence of treatment introduction and up-titration, description of GDMT implementation in the specific HF population, main causes of GDMT underuse, and assessment of cumulative rate of cardiovascular events. CONCLUSION: The OPTIPHARM-HF registry will provide important implications for improving patient care and adoption of recommended medical therapy into clinical practice among HF patients.

Strike early-strike strong lipid-lowering strategy with PCSK9i in ACS patients. Real-world evidence from AT-TARGET-IT registry.

AIMS: No data are available on early initiation of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in patients with acute coronary syndrome (ACS) in real-world. This study investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major CV events in real-world. METHODS: The lipid control outcome was the percentage of patients reaching the LDL-C target of < 55 mg/dL at first lipid control. The clinical outcome was the incidence of composite major CV events (all cause death, non-fatal MI, non-fatal stroke, and ischemia-driven revascularization) during follow-up in relation to quartiles of LDL-C at first lipid control. RESULTS: We included 771 patients with ACS from AT-TARGET-IT registry, receiving PCSK9i prescription during hospitalization or at discharge. Median LDL-C was 137 mg/dL and decreased to 43 mg/dL at first lipid control. 527 (68.3%) patients achieved LDL-C target at the first lipid control at a median time of 37 days from hospitalization; of them, 404 (76.8%) were discharged on statin plus ezetimibe background therapy. Event curves through a median follow-up of 11 months across quartiles of LDL-C showed a stepwise lower risk of 4P-MACE, 3P-MACE, all-cause mortality, and ischemia-driven revascularization in lower quartile of LDL-C values at first lipid control (<23 mg/dL) and in patients reaching LDL-C <55 mg/dL. CONCLUSIONS: Intensive and early lipid-lowering therapy using PCSK9i in patients with ACS (strike early strike strong strategy) is safe and effective in clinical practice and associated with a reduction of residual CV risk.

This study, from AT-TARGET-IT registry, investigates the effects of PCSK9i started at time of ACS hospitalization on lipid control and major CV events in real-world. Intensive and early PCSK9i therapy reduce composite major cardiovascular (CV) events in patients in reaching LDL-C target values. A strike early-strike strong strategy is safe and effective.

[ANMCO/SIC Consensus statement on pulmonary arterial hypertension]. / Documento di consenso ANMCO/SIC sull'ipertensione arteriosa polmonare.

Pulmonary hypertension (PH) is a frequent pathological condition worldwide, mainly secondary to cardiovascular and respiratory diseases, with a poor prognosis. Pulmonary arterial hypertension (PAH) is a rare form that affects the arterial pulmonary vasculature. PH and PAH are characterized by non-specific symptoms and a progressive increase of pulmonary vascular resistance that results in progressive, sometimes irreversible, right ventricular dysfunction. In recent years, a growing medical and social commitment on this disease allowed more accurate diagnosis in shorter times. However, the gap between guidelines and clinical practice remains a challenge for all medical doctors involved in the disease management. Considering the needs to share and describe diagnostic and therapeutic pathways, to measure the results obtained and to address the economical and organizational problems of this disease, all involved figures should collaborate to improve its prognostic impact and health expenses. In this consensus document, the PH experts of the Italian Association of Hospital Cardiologists (ANMCO) together with those of the Italian Society of Cardiology (SIC), address 1) definition, classification and unmet needs of PH and PAH; 2) classification and characteristics of centers involved in the diagnosis and treatment of the disease; 3) proposal of organization of a diagnostic-therapeutic pathway, based on robust and recent scientific evidence.

Isolated Valve Amyloid Deposition in Aortic Stenosis: Potential Clinical and Pathophysiological Relevance.

Amyloid deposition within stenotic aortic valves (AVs) also appears frequent in the absence of cardiac amyloidosis, but its clinical and pathophysiological relevance has not been investigated. We will elucidate the rate of isolated AV amyloid deposition and its potential clinical and pathophysiological significance in aortic stenosis (AS). In 130 patients without systemic and/or cardiac amyloidosis, we collected the explanted AVs during cardiac surgery: 57 patients with calcific AS and 73 patients with AV insufficiency (41 with AV sclerosis and 32 without, who were used as controls). Amyloid deposition was found in 21 AS valves (37%), 4 sclerotic AVs (10%), and none of the controls. Patients with and without isolated AV amyloid deposition had similar clinical and echocardiographic characteristics and survival rates. Isolated AV amyloid deposition was associated with higher degrees of AV fibrosis (p = 0.0082) and calcification (p < 0.0001). Immunohistochemistry analysis suggested serum amyloid A1 (SAA1), in addition to transthyretin (TTR), as the protein possibly involved in AV amyloid deposition. Circulating SAA1 levels were within the normal range in all groups, and no difference was observed in AS patients with and without AV amyloid deposition. In vitro, AV interstitial cells (VICs) were stimulated with interleukin (IL)-1ß which induced increased SAA1-mRNA both in the control VICs (+6.4 ± 0.5, p = 0.02) and the AS VICs (+7.6 ± 0.5, p = 0.008). In conclusion, isolated AV amyloid deposition is frequent in the context of AS, but it does not appear to have potential clinical relevance. Conversely, amyloid deposition within AV leaflets, probably promoted by local inflammation, could play a role in AS pathophysiology.