[The IN-HF Registry: the history and the scientific production for the Italian cardiology community]. / Il programma IN-HF: la storia e la produzione scientifica a favore della comunità cardiologica italiana.

The Italian Network on Congestive Heart Failure (IN-CHF) project, later known as IN-HF Online, was launched in 1995 to provide the Italian cardiology community with a digital tool, standardized across the country, for managing outpatients with heart failure (HF), that enabled the creation of a database for clinical, educational and scientific purposes. During its almost three decades of activity, this observational research program has achieved highly positive scientific results. Indeed, IN-HF fostered professional relationships among individuals working in different centers, established a cultural network for the care of HF patients, periodically updated on the scientific advances, and allowed the assessment of several clinical, epidemiological, and prognostic features. These findings have been published in numerous national and international journals, as summarized in the present overview.

[ANMCO Scientific statement on combination therapies and polypill in secondary prevention]. / Scientific statement ANMCO sulla semplificazione del regime terapeutico farmacologico in prevenzione secondaria.

The issue of suboptimal drug regimen adherence in secondary cardiovascular prevention presents a significant barrier to improving patient outcomes. To address this, the utilization of drug combinations, specifically single pill combinations (SPCs) and polypills, was proposed as a strategy to simplify treatment regimens. This approach aims to enhance treatment accessibility, affordability, and adherence, thereby reducing healthcare costs and improving patient health. The document is an ANMCO scientific statement on simplifying drug regimens for secondary cardiovascular prevention. It discusses the underuse of treatments despite available, effective, and accessible options, highlighting a significant gap in secondary prevention across different socioeconomic statuses and countries. The statement explores barriers to implementing evidence-based treatments, including patient, healthcare provider, and system-related challenges. The paper also reviews international guidelines, the role of SPCs and polypills in clinical practice, and their economic impact, advocating for their use in secondary prevention to improve patient outcomes and adherence.

Clinical characteristics, treatment, trajectories and outcome of patients with dilated cardiomyopathy in a national heart failure registry.

BACKGROUND: Available data on the clinical characteristics and prognosis of patients with heart failure (HF) due to dilated cardiomyopathy (DCM) derive mainly from tertiary care centres for cardiomyopathies or from drug trial sub-studies, which may entail a referral bias. METHODS: From 2008 to 2021, we enrolled in a nationwide HF Registry 1886 DCM patients and 3899 with ischemic heart disease (IHD). RESULTS: Patients with DCM were younger, more often female, had more commonly recent onset HF, left bundle branch block, and showed higher LV end-diastolic volume and lower LVEF than IHD. With respect to IHD, DCM patients received more often mineralocorticoid receptor antagonists, renin angiotensin system inhibitors and betablockers, the latter more commonly at doses ≥50% of target, and triple guideline-directed medical therapy (GDMT) (adjusted OR 1.411, 95% CI 1.247-1.595, p < .0001). During one-year follow-up, 819 patients (14.2%) died or were hospitalized for HF [187 (9.9%) DCM, 632 (16.2%) IHD]; DCM was associated with lower risk of the combined end-point (adjusted HR 0.745, 95% CI 0.625- 0.888, p = .0011). Among the 1954 patients with 1-year echocardiograms available, 1483 had LVEF≤40% at baseline; of these,166 (30.6%) DCM and 165 (17.5%) IHD improved their LVEF to >40% (p < .0001). DCM aetiology was associated with higher likelihood of LVEF improvement (adjusted OR 1.722, 95% CI 1.328 -2.233, p < .0001). CONCLUSIONS: DCM patients have a different clinical profile, greater uptake of GDMT and better outcomes than IHD subjects. A comprehensive management approach is needed to further address the risk of unfavorable outcomes in DCM.

[ANMCO Position paper: Colchicine as a therapeutic agent in coronary syndromes]. / Position paper ANMCO: La colchicina come agente terapeutico nelle sindromi coronariche.

With the growing knowledge about the role of inflammatory processes in the pathogenesis of atherosclerotic lesions, inflammation has been identified as a cardiovascular risk factor and therapeutic target to reduce the residual risk in patients with atherosclerotic disease. Several therapeutic agents with anti-inflammatory action have been tested to evaluate their efficacy and safety in the context of atherosclerotic cardiovascular diseases. Among these, colchicine, a drug with multiple therapeutic effects including anti-inflammatory action, in randomized clinical trials conducted in the setting of atherosclerotic cardiovascular disease secondary prevention, significantly reduced the risk of adverse cardiovascular events.This position paper of the Italian Association of Hospital Cardiologists (ANMCO) summarizes the main biological mechanisms through which colchicine contributes to the inhibition of inflammatory processes that increase the atherosclerotic cardiovascular risk. Furthermore, the document reports the available evidence on clinical impact of colchicine treatment in the reduction of residual cardiovascular risk in chronic and acute coronary syndromes. Finally, practical information is provided regarding the use of this drug in this specific clinical setting, emphasizing precautions and possible side effects.

Treatment of amyloidosis: present and future.

Cardiac amyloidosis (CA) is an infiltrative heart disease resulting from the deposition of amyloid fibrils in the interstitial spaces of the myocardium. The two main forms of CA are represented by light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR) in the two forms familial or variant or wild-type or senile. Although considered a rare disease, CA is an underdiagnosed disease. Delay in diagnosis has a negative impact on the prognosis, delaying the initiation of specific therapy. The treatment of both forms of CA is based on: (i) prevention and slowing of the generation and deposition of amyloid fibrils and (ii) supportive care of complications. The main success of recent years has been the development of effective therapies that have been possible thanks to the understanding of the pathophysiology of amyloidosis. For the AL form, new therapeutic combinations between a proteasome inhibitor and a monoclonal antibody have been developed. For ATTR forms, the main strategies are transthyretin (TTR) production 'silencers' and TTR tetramer stabilizers. Supportive care of patients with CA involves various clinical aspects including treatment of heart failure, arrhythmias, conduction disturbances, thrombo-embolism, and the concomitant presence of aortic stenosis.

[ANMCO Position paper: Evidence and practical indications for the use of low-dose rivaroxaban in stable coronary artery disease and peripheral artery disease]. / Position paper ANMCO: Evidenze e indicazioni pratiche per l'impiego di rivaroxaban a bassa dose nella malattia coronarica stabile e nell'arteriopatia periferica.

In patients with atherosclerotic disease, the occurrence of atherothrombotic events is the main determinant of morbidity and mortality. Growing evidence suggests the involvement of the coagulation pathway in the atherosclerotic process and the benefit of antithrombotic agents, such as direct oral anticoagulants, which interfere with both platelet aggregation and the coagulation cascade. The COMPASS trial has shown that in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD), low-dose rivaroxaban (2.5 mg twice daily) added to acetylsalicylic acid (ASA) 100 mg reduces major vascular events and mortality, with an increase in major bleeding but not in fatal bleeding or involving a critical organ. The reduction in major cardiovascular events has been confirmed in the overall population with CAD and in both patients with and without a previous percutaneous coronary revascularization, and also in patients with previous coronary bypass surgery. In patients with PAD, the combination of rivaroxaban 2.5 mg twice daily and ASA was found to reduce both major adverse cardiovascular events and major adverse limb events, including major limb amputations. In clinical practice, the use of rivaroxaban 2.5 mg co-administered with ASA has been approved in both patients with CAD and symptomatic PAD at high risk of ischemic events. However, in Italy, the national health system reimbursement is provided only for patients with PAD. In patients treated with rivaroxaban 2.5 mg, assessment and monitoring of bleeding risk is crucial to achieve the maximum clinical benefit.

Selection of patients eligible for implantable cardioverter defibrillator: beyond left ventricular ejection fraction.

The selection of patients eligible for implantable cardioverter defibrillator (ICD), in primary prevention, is a critical moment in the management of the patients with cardiomyopathies as it needs a right balance of the patients' arrhythmic risk and the risks related to the implantation, as well as the device costs. Several data indicate that left ventricular ejection fraction alone is not a sufficient criterion for a proper identification of patients who could benefit most from ICD. Numerous findings show that genetic analysis and characterization of myocardial fibrosis with magnetic resonance imaging allow an important improvement of this process.

Moderate gradient severe aortic stenosis: diagnosis, prognosis and therapy.

Aortic stenosis (AS) is defined as severe in the presence of: mean gradient ≥40 mmHg, peak aortic velocity ≥4 m/s, and aortic valve area (AVA) ≤1 cm2 (or an indexed AVA ≤0.6 cm2/m2). However, up to 40% of patients have a discrepancy between gradient and AVA, i.e. AVA ≤1 cm2 (indicating severe AS) and a moderate gradient: >20 and <40 mmHg (typical of moderate stenosis). This condition is called 'low-gradient AS' and includes very heterogeneous clinical entities, with different pathophysiological mechanisms. The diagnostic tools needed to discriminate the different low-gradient AS phenotypes include colour-Doppler echocardiography, dobutamine stress echocardiography, computed tomography scan for the definition of the calcium score, and recently magnetic resonance imaging. The prognostic impact of low-gradient AS is heterogeneous. Classical low-flow low-gradient AS [reduced left ventricular ejection fraction (LVEF)] has the worst prognosis, followed by paradoxical low-flow low-gradient AS (preserved LVEF). Conversely, normal-flow low-gradient AS is associated with a better prognosis. The indications of the guidelines recommend surgical or percutaneous treatment, depending on the risk and comorbidities of the individual patient, both for patients with classic low-flow low-gradient AS and for those with paradoxical low-flow low-gradient AS.

Chronic aspirin and statin therapy in patients with impaired renal function and acute coronary syndromes: results from the IN-ACS Outcome Registry.

BACKGROUND: The cardioprotective role that statin and aspirin has appears to be reduced in patients with chronic kidney disease (CKD). This analysis aims to evaluate the impact of statin and aspirin on the outcome of patients with CKD and acute coronary syndrome (ACS). METHODS: All patients who were enrolled in the IN-ACS Outcome registry, diagnosed with CKD, were included in our analysis. We divided patients into four groups, according to previous chronic therapy: neither aspirin nor statin therapy (Group 1), aspirin only therapy (Group 2), statin only therapy (Group 3) and aspirin plus statin therapy (Group 4). RESULTS: Of the 5483 patients enrolled that had data on glomerular filtration rate available, 1484 had CKD: These segregated into 589 patients in Group 1, 477 in Group 2, 89 in Group 3 and 329 in Group 4. Despite having a higher baseline risk profile, groups 3 and 4, as compared to the other two groups, exhibited a significantly lower in-hospital mortality (1% in Group 3, 2% in Group 4; but 8% in Group 1 and 7% in Group 2, p = 0.0007); while at 30 days it remained so, as it was 1% in Group 3, 4% in Group 4 (and 10% in Group 1 and 10% in Group 2 p = 0.0002); and at 1 year it was 11% in Group 3 and 13% in Group 4 (compared to 20% in Group 1 and 23% in Group 2, p = 0.0012). CONCLUSIONS: In a large cohort of patients with CKD and ACS, chronic treatment with statin or the combination of aspirin and statin is associated with short-term and long-term better outcomes for in-hospital mortality, as compared to those receiving no therapy or aspirin therapy alone.

Prevalence of preclinical and clinical heart failure in the elderly. A population-based study in Central Italy.

AIMS: We conducted a population-based cross-sectional study to assess the prevalence of both preclinical and clinical heart failure (HF) in the elderly. METHODS AND RESULTS: A sample of 2001 subjects, 65- to 84-year-old residents in the Lazio Region (Italy), underwent physical examination, biochemistry/N-terminal pro brain natriuretic peptide (NT-proBNP) assessment, electrocardiography, and echocardiography. Systolic left ventricular dysfunction (LVD) was defined as left ventricular ejection fraction (LVEF) <50%. Diastolic LVD was defined by a Doppler-derived multiparametric algorithm. The overall prevalence of HF was 6.7% [95% confidence interval (CI) 5.6-7.9], mainly due to HF with preserved LVEF (HFpEF) (4.9%; 95% CI 4.0-5.9), and did not differ by gender. A systolic asymptomatic LVD (ALVD) was detected more frequently in men (1.8%; 95% CI 1.0-2.7) than in women (0.5%; 95% CI 0.1-1.0; P = 0.005), whereas the prevalence of diastolic ALVD was comparable between genders (men: 35.8%; 95% CI = 32.7-38.9; women: 35.0%; 95% CI = 31.9-38.2). The NT-proBNP levels and severity of LVD increased with age. Overall, 1623 subjects (81.1% of the entire studied population) had preclinical HF (Stage A: 22.2% and stage B: 59.1% respectively). A large number of subjects in stage B of HF showed risk factor levels not at target. CONCLUSIONS: In a population-based study, the prevalence of preclinical HF in the elderly is high. The prevalence of clinical HF is mainly due to HFpEF and is similar between genders.

Clinical epidemiology, management and outcome of acute coronary syndromes in the Italian network on acute coronary syndromes (IN-ACS Outcome study).

BACKGROUND: The Italian network on acute coronary syndromes outcome (IN-ACS Outcome) study is a nationwide observational, multicenter study with the aim to describe clinical epidemiology, management, 30-days and one-year outcomes of ACS in Italy. METHODS: All consecutive patients admitted for ACS to 38 hospitals, between December 2005 and February 2007, were enrolled in the study. Patient in-hospital details and follow-up data at 30-days and one-year were collected using a web-based CRF and stored in a central database. RESULTS: A total of 6045 patients (age 68 ± 13 years) were enrolled: 2313 patients (38.3%) had ST elevation myocardial infarction (STEMI) and 3732 (61.7%) patients had NSTE-ACS. Primary PCI was performed in 1085 (46.9%) STEMI patients, thrombolysis in 590 (25.5%) patients, whereas 638 (27.6%) patients were not reperfused. Among patients with NSTE-ACS, coronary angiography was performed in 2797 (75%) patients, PCI in 1797 (48.2%) patients and CABG in 213 (5.7%) patients. Thirty-days and one-year mortality rates were 5.8% and 9.8%, in STEMI patients and 3.1% and 8.6%, in NSTE-ACS patients. CONCLUSIONS: The IN-ACS Outcome study showed that the management of ACS is still suboptimal. Although 30-days mortality is low, the one-year mortality is still substantial.

Paradoxical preservation of vascular function in severe obesity.

BACKGROUND: Obesity is associated with a high risk of coronary artery disease morbidity and mortality. Yet, postmortem studies have shown that severely obese subjects exhibit smooth coronary arteries, thus suggesting that they may be protected from atherosclerosis. We assessed vascular function and its possible determinants in a cohort of normal-weight to severely obese insulin-sensitive subjects (body mass index [BMI] 23.2-49 kg/m(2)). METHODS: Seventy-one healthy, insulin-sensitive subjects (Homeostasis Model Assessment of Insulin Resistance index <2.5), divided into normal-weight (n = 13; BMI = 23.2 +/- 1.6), obese (n = 35; BMI=32.6+/-2.5), and severely obese (n=23; BMI=49.0+/-7.9) groups, were enrolled. Vascular function was evaluated by flow-mediated dilation and carotid intima-media thickness. High-sensitivity C-reactive protein, leptin, adiponectin, vascular growth factors, and CD34+KDR+/CD133+ endothelial progenitor cells, known markers of vascular health/protection, also were measured. RESULTS: Flow-mediated dilation was higher in severely obese than in obese and normal-weight individuals (P=.019 and P=.011 respectively). Intima-media thickness was consistently lower in severely obese than in obese individuals (P=.040) and similar in severely obese and normal-weight individuals (P >.99). Levels of high-sensitivity C-reactive protein and leptin were higher in severely obese than in obese and normal-weight individuals (high-sensitivity C-reactive protein: P=.018 and P=.05, respectively; leptin: P <.001 for both comparisons). CD34+KDR+ endothelial progenitor cells were significantly higher in severely obese versus obese individuals (P=.039). CONCLUSION: Our study demonstrates that vascular function is paradoxically better in severely obese than in obese subjects and similar to that found in normal-weight subjects. Despite higher levels of high-sensitivity C-reactive protein and leptin, severely obese individuals may be partially protected from atherosclerosis, possibly by a greater mobilization of endothelial progenitor cells.

Role of the CD14 C(-260)T promoter polymorphism in determining the first clinical manifestation of coronary artery disease.

BACKGROUND: Acute coronary syndromes (ACS) and chronic stable angina represent extremes of the clinical spectrum of coronary artery disease (CAD). It is unknown whether genetic determinants affect the first clinical manifestation of CAD. We evaluated the role of the C(-260)T polymorphism in the promoter of the CD14-receptor gene, an important mediator of the inflammatory response to lipopolysaccharide. METHODS AND RESULTS: CD14 C(-260)T polymorphism was assessed in 100 patients with an acute presentation of CAD (group 1), 66 patients with stable presentation (group 2) and 88 healthy people (group 3); all patients were whites. In addition, baseline sCD14 plasma levels, and interleukin-6 production by circulating monocytes after in-vitro stimulation with lipopolysaccharide (1 ng/ml) were assessed. T/T homozygosis was more frequent in group 1 (36%, P < 0.001 versus others). Interleukin-6 production was higher in T/T homozygotes (median 4092.4; range 387-10 582 pg/ml) than in C/T heterozygotes (median 2442, range 40.5-9625 pg/ml, P < 0.001) and C/C homozygotes (median 3277.5; range 374.4-6250 pg/ml, P < 0.001). At multivariate analysis, T/T homozygosis and interleukin-6 production were independent predictors of acute presentation of CAD. CONCLUSION: The present study shows that genetic factors that influence the reactivity of inflammatory cells may play a role in determining the first clinical presentation of CAD.

Prognostic significance of QRS duration in patients with suspected coronary artery disease referred for noninvasive evaluation of myocardial ischemia.

The purpose of this study was to evaluate the prognostic significance of QRS duration in patients with suspected coronary artery disease (CAD) referred for noninvasive evaluation of myocardial ischemia by dobutamine stress echocardiography. QRS duration is a prognostic marker in patients with previous myocardial infarction and/or heart failure. The relation between QRS duration and outcome of patients without known heart disease has not been evaluated. A total of 1,227 patients (707 men, mean age 61 +/- 14 years) with suspected CAD underwent dobutamine stress echocardiography for evaluation of myocardial ischemia. Patients were followed to determine predictors of cardiac events and to assess the incremental significance of QRS duration compared to clinical and dobutamine stress echocardiographic data. During a mean follow-up of 4.2 +/- 2.4 years, 280 patients (23%) died (129 cardiac deaths), and 60 (5%) had a nonfatal infarction. Annualized cardiac death rates were 2.0% in patients with QRS duration <120 ms and 4.4% in patients with QRS duration >or=120 ms, respectively (p <0.0001). Annualized event rates for cardiac death/nonfatal infarction were 2.8% in patients with QRS duration <120 ms and 4.8% in patients with QRS duration >or=120 ms (p = 0.0001). Multivariate models identified age, male gender, smoking, QRS duration >or=120 ms, and an abnormal dobutamine stress echocardiogram as independent predictors of cardiac death and the combined end point cardiac death/nonfatal infarction. In conclusion, QRS duration is an independent predictor of cardiac death and cardiac death/nonfatal infarction in patients with suspected CAD. This risk is persistent after adjustment for clinical variables, left ventricular function, and myocardial ischemia.

Different apparent prognostic value of hsCRP in type 2 diabetic and nondiabetic patients with acute coronary syndromes.

BACKGROUND: C-reactive protein (CRP) is an established prognostic marker in acute coronary syndromes (ACS); however, no study has specifically addressed its prognostic role in type 2 diabetes with ACS. We evaluated the prognostic role of CRP separately in diabetic and nondiabetic patients with ACS. METHODS: We enrolled 251 patients with unstable angina and measured serum concentrations of high sensitivity (hs)CRP. Ninety-seven patients underwent coronary angiography with evaluation of atherosclerotic disease severity and extent by Bogaty score. Assessed endpoint was the combined occurrence of myocardial infarction (MI) and death at 1 year. RESULTS: No significant differences were found in hs-CRP between patients with and without diabetes. By Cox regression, hsCRP was not associated with 1-year follow-up events in diabetic patients but was strongly associated with events in nondiabetic patients (P = 0.0012). Coronary angiography exhibited a higher extent index in patients with diabetes than in those without (P = 0.04). hsCRP concentrations were not associated with angiographic atherosclerotic burden. By Cox analysis, hsCRP and extent score were associated with events in patients who underwent coronary angiography (P < 0.001 and P = 0.034, respectively). In nondiabetic patients, hsCRP was the only predictor of events at 1-year follow-up (P < 0.001), whereas in diabetic patients, hsCRP was not associated with events and a weak association was observed for extent score (P = 0.06). CONCLUSIONS: Our study suggests that different pathophysiological mechanisms may be responsible for MI and death in unstable angina patients with or without diabetes and that severity of coronary artery disease plays a major role in diabetes (and inflammation in the absence of diabetes).

Magnetic resonance imaging of carotid plaque inflammation in acute coronary syndromes: a sign of multisite plaque activation.

Widespread plaque inflammation has been demonstrated in acute coronary syndromes (ACS). We evaluated signs of plaque inflammation in carotid arteries of patients with ACS by contrast-enhanced magnetic resonance imaging (MRI). Carotid MRI was performed in 13 patients with ACS and in 9 controls having at least 1 carotid plaque with a stenosis > or =40%. MRI criteria of plaque inflammation were: increased T2 signal >50% of the plaque areas (tissue oedema) and/or enhancement after gadolinium injection (neo-vascularization). MRI signs of inflammation were found in 95% and in 33% of patients with ACS and controls, respectively (p<0.001). Carotid artery MRI may serve as a window to the entire cardiovascular system, to identify "vulnerable" patients.

Entrapment of a floating thrombus in the right atrium by persistent Chiari's network: a barrier to massive pulmonary embolism.

Syncope may be a manifestation of pulmonary embolism. Occlusion of a pulmonary artery with cardiac output drop, sometimes resulting in cardiac arrest, is the main underlying mechanism. In this letter we describe the case of a patient in which the persistence of a long remnant of the embryonal Chiari's network could have worked as an anatomic barrier preventing massive pulmonary embolism and cardiac arrest.

Transient global amnesia during transoesophageal echocardiogram.

Transient global amnesia (TGA) is a common paroxysmal disorder of episodic memory. The aetiology of TGA is still unknown. Brain ischaemia, migraine, epileptic seizure, venous congestion and psychological disturbances have been proposed as pathological mechanisms. Moreover, different precipitating events are recognised in most TGA patients including physical activity, severe emotional stress, painful experiences, immersion in cold water and sexual intercourse. We describe a 54-year-old woman who presented a TGA immediately after right-left shunt of saline contrast during the execution of transoesophageal echocardiography. Aetiopathological considerations for this uncommon presentation are discussed.

Osteoprotegerin and B-type natriuretic peptide in non-ST elevation acute coronary syndromes: relation to coronary artery narrowing and plaques number.

BACKGROUND: To analyse osteoprotegerin (OPG), and B-type natriuretic peptide (BNP) levels in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), in relation to clinical presentation and to coronary atherosclerosis diffusion. OPG has been found in several tissues, including the cardiovascular system, BNP is selectively produced by myocardial cells. METHODS: 178 consecutive patients were classified in three groups: stable angina (SA), unstable angina/non-ST elevation myocardial infarction (NSTE-ACS) and control group, measuring OPG and BNP at hospital admission. We compared both biomarkers in relation to the number of coronary narrowed vessels (1-, 2- , 3- or 4- vessels disease), and to the stenoses degree by Duke Jeopardy score. RESULTS: OPG levels were higher in patients respect to controls (p<0.0001). Patients with SA showed more elevated levels than controls (2.6+/-1.2 vs 7.4+/-5.0 pmol/l p<0.01). However patients with NSTE-ACS had higher OPG level with respect to SA patients (11.8+/-7.1 pmol/l p<0.001). A positive relation was found between OPG levels and number of coronary plaques by Duke Jeopardy score (r=0.65). BNP levels were higher in patients with NSTE-ACS respect to controls and SA patients (p<0.001). Besides, BNP was significantly higher in multivessels vs 1-vessel disease (p<0.001). CONCLUSIONS: Patients with NSTE-ACS show high OPG levels. OPG increase seems related to the number of plaques in the coronary vessels, suggesting its involvement in the coronary disease progression. BNP is also increased during NSTE-ACS and more associated to coronary narrowing.