Clinical trials

Mitral and tricuspid valve disease represents an increasing challenge in the management of patients with heart failure and other cardiovascular diseases. In recent years, the introduction of transcatheter techniques for valve repair and replacement (TVI) has revolutionised the treatment of these diseases, particularly for patients at high surgical risk or who are not candidates for traditional surgery. However, although these procedures are increasingly popular, their long-term effectiveness in terms of cardiac remodelling is still not well understood. Cardiac magnetic resonance (CMR) techniques, with their advanced capabilities to provide anatomical and functional details of the heart, offer a unique opportunity to assess ventricular remodelling and valve function before and after transcatheter interventions. The ESC guidelines on valvulopathies published in 2021 recommend the use of cardiac magnetic resonance imaging not only to quantify the extent of mitral and tricuspid regurgitation when echocardiography is inconclusive, but also as the gold standard for the assessment of left and right ventricular size and function (limited, however, to the availability of this method in the various centres). Currently, there are few systematic data evaluating the effect of these procedures on CMR-assessed cardiac anatomy and function. This study aims to fill this gap by creating a multicentre registry in which clinical and advanced imaging data, including 3D echocardiography and CMR, are collected to assess the impact of these therapies. Analysis of data derived from advanced imaging will not only provide a better understanding of the mechanism of operation of transcatheter techniques, but will also provide important information for improving long-term patient outcomes by identifying potential predictors of treatment success or failure.

Coronary computed tomography angiography (CCTA) is a non-invasive imaging tool that characterizes coronary artery anatomy and provides detailed assessments of plaque morphology, composition , inflammation, and hemodynamics, which have crucial prognostic implications. The FASTTRACK CABG trial demonstrated that CCTA- fractional flow reserve derived from CCTA can plan and guide coronary artery bypass grafting treatment without traditional invasive coronary angiography and provides a valuable dataset of pre- and post-CABG CCTA for further research. This study is a sub-analysis of the FASTTRACK CABG trial and aims first of all to assess whether these imaging-derived markers can predict symptomatic relief and clinical outcomes for patients undergoing CABG, for complex three-vessel or left main coronary artery disease. Moreover, human coronary lesion studies from subjects with sudden death and carotid endarterectomy specimens demonstrate increasing levels of Lipoprotein(a) with lesion progression, peaking in ruptured plaques. Lp(a) is a low-density lipoprotein (LDL)-like particle comprising an apolipoprotein (apoB-100 molecule covalently linked to apo(a). Genome-wide association and Mendelian randomization studies provide strong evidence for the causal association between elevated Lp(a) levels and atherosclerotic cardiovascular diseases (ASCVD) risk. Current clinical guidelines, including the 2022 European Atherosclerosis Society (EAS) consensus, recommend measuring Lp(a) levels at least once in an adult's lifetime. Circulating Lp(a) levels remain relatively stable over a lifetime, making single measurements cost-effective for risk assessment. Established thresholds for high-risk Lp(a) levels are \>50 mg/dL or 125 nmol/L, as recognized by assays standardized to WHO/International Federation of Clinical Chemistry guidelines. Epidemiological data suggest that Lp(a) \>30 mg/dL increases the risk of coronary heart disease and myocardial infarction, while levels \>50 mg/dL elevate the risk of ischemic stroke. Approximately 20-25% of the general population has elevated serum Lp(a) levels. Despite robust evidence linking Lp(a) to ASCVD risk, data correlating Lp(a) levels with coronary artery calcium (CAC) progression remain limited. While Lp(a) and CAC independently predict ASCVD risk, their combined role in guiding prevention strategies is underexplored. Lipoprotein(a)-lowering strategies are currently being investigated in phase 3 cardiovascular outcomes trials. Specifically, the correlation between serum Lp(a) levels and CCTA-derived total calcified plaque volume has yet to be comprehensively studied.

This is a prospective, observational, multicenter study aimed at characterizing tricuspid valve remodeling in patients with atrial fibrillation (AF) without significant tricuspid regurgitation (TR), in relation to AF burden progression.

Coronary artery disease (CAD) is among the leading cause of death and disability. Identification of patients at high risk of cardiovascular events is pivotal. However, current risk stratification based on imaging and known biomarkers is suboptimal. The objective of this proposal is to develop a multicriteria decision model for non-invasive assessment of vulnerable atherosclerotic patients and to evaluate its ability to predict the occurrence of an adverse event in intermediate-to-high risk patients with suspected or known CAD. The planned workflow includes a first step using a retrospective cohort of patients undergoing clinically indicated coronary angiography (CCTA) to develop an integrated application for automatic coronary artery segmentation, quantitative plaque analysis, biomechanics and fluid dynamics, based on machine learning, radiomics and computational analysis approaches and validated against the reference standard for each tool. The second step will apply this new methodology to a larger retrospective cohort of patients with the integration of genomic biomarker assessment to derive the most accurate risk stratification model to properly identify vulnerable patients and vulnerable plaques with respect to outcome. Finally, in the third step, the derived predictive model will be prospectively validated in an independent cohort of patients from an ongoing study (CTP-PRO study) to assess the robustness and accuracy of the proposed solution.

The study of calcifications involving the mitral valve is extremely important for the planning of both surgical and percutaneous procedures. Computed tomography (CT) is the non-invasive imaging modality considered the gold standard for the assessment of mitral valve calcifications, thanks to its high spatial resolution and the strong X-ray attenuation of calcium deposits. Echocardiography has traditionally played a limited role in the evaluation of mitral valve calcifications, particularly with three-dimensional imaging. Three-dimensional transesophageal echocardiographic rendering with TrueVue transillumination (Philips Medical Systems, Eindhoven, NL) can provide additional information on the location and extent of calcium on the mitral valve by allowing the placement of a virtual light source beneath the mitral valve. Specifically, the TrueVue system is an advanced software module integrated into Philips echographic equipment that uses data acquired by the transesophageal probe to generate photorealistic images of the heart. Therefore, the ability to evaluate the position and extent of calcifications through transesophageal echocardiography may represent an important step forward for echocardiographic imaging.

This observational study aims at validating the Italian Self-care of Heart Failure Index (SCHFI) v.8 and the Caregiver Contribution to Self-care of Heart Failure Index (CC-SCHFI) v.3

Detection of coronary stenosis is of utmost importance in identifying vulnerable patients. The combined use of coronary computed tomography angiography at rest (CCTA) and stress myocardial computed tomography perfusion (stress-CTP) provides both anatomic and functional analysis of coronary artery disease (CAD) using a single imaging test. Stress-CTP evaluates myocardial perfusion by measuring myocardial blood flow (MBF) under pharmacologically induced stress conditions. The drawback is that stress-CTP requires additional scanning and administration of an intravenous stressor with an increase in radiation exposure and potential stressor-related side effects. The investigators recently patented a computational model that can reproduce MBF under stress conditions (Italian patent n. 102021000031475 Metodo implementato mediante computer per la simulazione del flusso sanguigno miocardico in condizioni di stress \[Computational method for simulating myocardial blood flow in stress conditions\], half owned by Centro Cardiologico Monzino, half by Politecnico di Milano). On top of this, CCTA can characterize plaque type and identify adverse plaque characteristics. Moreover, biomechanics analysis allows the study of luminal stenosis and stress within the plaque. Finally, radiomics, extracting quantitative features from medical images to create big data and identify novel imaging biomarkers, can be applied to improve the diagnostic accuracy of coronary plaques.

This is a multicenter, observational prospective and retrospective study which aims are: 1) to compute a scoring model potentially predictive for the diagnosis of fibrosis by CMR in patients with MVP; 2) to identify specific features that may predispose to ≥ mild VAs or SCD in patients with MVP.

The goal of this clinical trial is to learn if Atorvastatin 80 mg is effective to avoid functional right ventricular deterioration in patients affected by Arrhythmogenic Cardiomyopathy. It will also learn about the safety of Atorvastatin 80 mg in this type of patients. The main questions it aims to answer are: 1. Does Atorvastatin 80 mg prevent worstening of the right ventricular functioning? 2. Does Atorvastatin 80 mg prevent the worsening of electric, morphological and biomarkers deterioration? 3. What medical problems do participants have when taking Atorvastatin 80 mg? Researchers will compare Atorvastatin 80 mg to a placebo (a look-alike substance that contains no drug) to see if the drug works to treat Arrhythmogenic Cardiomyopathy. Participants will: 1. Take Atorvastatin 80 mg or a placebo every day for 18 months; 2. Visit the clinic at the enrollment and after 2, 4, 9 and 18 months for checkups and tests; 3. Make a phone call for safety check after 12, 15 and 19 months since the enrollment; 4. Fill out psychological questionnaires

Patients on oral anticoagulant therapy with vitamin K antagonists (AVKs; warfarin and acenocoumarol) and direct oral anticoagulants (DOACs; apixaban, dabigatran, edoxaban and rivaroxaban), are advised to consider discontinuing treatment in anticipation of invasive manoeuvres. Guidelines and expert consensus recommend, in clinical conditions with a high risk of bleeding, to suspend oral anticoagulant treatment with DOACs 2 or 3 days before the procedure, depending on the glomerular filtrate, to suspend warfarin from day -5 and acenocoumarol from day -4, and to introduce heparins from day -3 after discontinuation of AVKs (so-called 'bridging therapy') for manoeuvres with a high risk of bleeding. In manoeuvres with a low bleeding risk it is possible not to suspend the anticoagulant or to reduce its intensity. Obviously, the patient's intrinsic haemorrhagic and thrombotic risk (antiplatelet intake, renal insufficiency, hepatopathy, age, mechanical valve prosthesis, oncological condition, etc.) must also be taken into account in the overall assessment of pre-procedural preparation. Gastroenterological endoscopic manoeuvres are generally considered to be at low haemorrhagic risk even if biopsy is planned, but are at high haemorrhagic risk if polypectomy or mucosectomy is planned. The most complex problem arises at the time of re-introduction of anticoagulant post-procedure. In fact, studies evaluating this specific aspect are very few and heterogeneous and mostly retrospective. The variables that are associated with an increased risk of bleeding are: the number and site of polypectomies, the diameter of the polyps, and local haemostasis techniques. Late haemorrhages (\>24 hours) are of concern because the patient is generally at home and because, by the time the eschar falls out (varying between 4 and 10 days post-procedure), they have already resumed anticoagulation. However, there are no prospective studies of sufficient number to clarify whether the reintroduction of anticoagulation modifies the haemorrhagic risk, when is the time of greatest risk after the procedure, and which variables associated with the patient and the procedure most modify the haemorrhagic risk.

The goal of this clinical trial is to learn if Infection Control Link Nurses (i.e., clinical nurses providing direct patient care with an interest and expertise in infection control practices) are effective in improving nurses' compliance with standard precaution measures, healthcare professional's compliance with hand hygiene practices and in reducing healthcare-associated infections. The main questions it aims to answer are: * Are Infection Control Link Nurses effective in improving nurses' compliance with standard precautions? * Are Infection Control Link Nurses effective in improving healthcare professionals' compliance with hand hygiene practices? * Are Infection Control Link Nurses effective in improving alcohol-based hand rub consumption? * Are Infection Control Link Nurses effective in reducing healthcare-associated infections? In this study, a total of 8 hospital units will be randomized in two groups: 1) Intervention group, where in 4 hospital units will be selected and trained 4 Infection Control Link Nurses; and 2) Control group, where in 4 hospital units will continue usual IPC practice. Training of Infection Control Link Nurses will be 12 months-long, with regular monthly scheduled meetings. Researchers will compare Intervention group with the Control group to see if nurses' compliance with standard precautions and healthcare professionals' compliance with hand hygiene will improve in the Intervention group, and if overall healthcare-associated infection incidence will decrease. Participants will be nurses working full time in the selected hospital units, for a total of 100 nurses. They will sign an Informed Consent form and they will fill out a validated instrument named "Compliance with Standard Precautions Scale-Italian Version", to measure their adherence to standard precautions measures (i.e., use of protective device, disposal of sharp, disposal of waste etc). Concurrently, evaluation of healthcare professionals' compliance with hand hygiene will be done via direct observation, following World Health Organization's Technical Manual, by hospital staff who did not participate in the conception and design of the study. Lastly, data regarding alcohol-based hand rub consumption and healthcare-associated infections will be collected by experienced personnel who routinely perform these activities. The study will last 12 months, data collection will be carried out at baseline (pre-implementation of infection control link nurses) and after 12 months (after infection control link nurses implementation).

Heart failure is a complex condition involving multiple organs beyond the cardiovascular system, all influencing disease progression and prognosis. Accurate risk assessment requires considering multiple variables, as no single parameter alone provides a complete prognostic picture. This has led to the development of prognostic models combining clinical and laboratory parameters. Some of these models incorporate cardiopulmonary exercise testing (CPET), which provides key prognostic indicators. Since the 1990s, CPET has been recommended in heart failure management guidelines due to its strong prognostic value when combined with clinical data. However, existing risk models often exclude important predictors such as ventilatory parameters from CPET (VE/VCO₂), renal function, and hemoglobin levels. To address this gap, in 2012 the investigators developed the MECKI (Metabolic Exercise test data combined with Cardiac and Kidney Indexes) score, integrating oxygen consumption, ventilatory efficiency, and easily accessible biochemical and echocardiographic parameters. Unlike previous models requiring extensive data collection, MECKI is based on only six variables, making it practical and effective. Recent studies suggest the need to update the cutoff values and parameters used for risk stratification, as new therapies and treatment strategies may significantly alter prognostic accuracy in different patient populations. This study aims to expand and refine the MECKI score by updating the patient dataset, optimizing its performance in specific subgroups, and aligning it with emerging therapeutic approaches. Additionally, the investigators will evaluate whether the model's risk accuracy varies in advanced-stage patients, those with comorbidities, or under different treatment regimens. This could lead to correction factors that enhance the score's predictive power across diverse clinical scenarios, further improving its applicability and reliability in heart failure management.

The study aims to explore the effects of body scan on enteroception in people with heart failure

This study aims to advance the understanding of cardiac amyloidosis, its effects on exercise capacity, and its prognostic implications. By conducting a systematic investigation with particular emphasis on longitudinal evaluation, we aim to provide valuable insights to guide clinical practice and improve the management of patients with cardiac amyloidosis. Our study intends to follow patients for a period of two years, evaluating them every six months. This longitudinal approach allows us to monitor changes in exercise capacity and other relevant clinical parameters over time. Furthermore, it enables the development of a prognostic tool similar to the MECKI score, capable of assessing the risk of adverse events in patients with cardiac amyloidosis based on their exercise performance. By comparing our results with data from heart failure patients already included in the MECKI score database, we also aim to highlight any differences in prognosis between patients with cardiac amyloidosis and those with general heart failure. Finally, we aim to characterize cardiac amyloidosis by differentiating it from general heart failure. By comparing our results with data from heart failure patients already included in the MECKI score database, we can clarify the distinct exercise limitations in cardiac amyloidosis and shed light on how they differ from more conventional heart failure.

As altitude increases, the availability of oxygen in the air decreases, and just to compensate for this lack, the body increases cardiac and respiratory work and changes blood pressure. But that is not all: at altitude the body's ability to use oxygen is also limited. Thus, there is on one hand less oxygen available, and on the other a lower capacity to use it. All this generates significant alterations at the cardiovascular level, to the point of running possible risks of heart attack, stroke and acute pulmonary edema, particularly for individuals already suffering from cardiovascular disease. The availability of modern cable cars allows an increasingly large number of individuals, including sedentary people, elderly subjects, and cardiorespiratory patients, to easily and rapidly reach high-altitude locations. Data on what happens on the cardiovascular system at high altitude are relatively scarce, and most experiments in the literature are limited by low sample sizes. The primary purpose of this study is to assess the characteristics of a large population that acutely reached high altitude at Punta Helbronner (3,466 m above sea level), a location on Mont Blanc that is readily accessible by a 20-minute cableway ride from Courmayeur (Entreves station, 1,300 m, Skyway Monte Bianco). We aim to create a unique database and study correlations between altitude and cardiorespiratory parameters (heart rate, blood pressure, and Hb saturation) by collecting medical history data and biometric measurements in a very large population and to identify subjects most at risk of developing hypoxia at altitude. In a subset of subjects, differences in biometric variables after acute exposure at high altitude (in the transition between the downstream and the upstream measuring station) will be evaluated. Two biometric multiparametric recording systems (Keito K9; Keito, Barcelona, Spain) were installed at Entreves station as well as at Punta Helbronner. Keito K9 is an automatic multiparametric recoding system for measuring peripheral oxygen saturation SpO2, heart rate HR (pulse oximeter), blood pressure (BP; wrist pressure cuff, automatic), height (laser height meter), weight (scale platform), and body mass index (BMI). Once initiated by the subject with the completion of a cardiology history questionnaire (self-reported), the automated Keito K9 system provides a sequence of vocal and animated directions to guide subjects through the measurements (the subject may elect to abstain from some of the measurements). Upon completion, the system prints a summary receipt for the subject, and the measurements are transmitted through a Wi-Fi network and collected in an Excel sheet. It should be noted that all data collected will be anonymized or not traceable to the subject, through the use of a disposable identification card (for subjects who will perform both downstream and upstream measurement).

Extracellular vesicles (EVs) play a key role in cell-to-cell communication. They are small vesicles that contain rich molecular cargo. Recently, they have been proposed as biomarkers for clinical diagnostics. EVs include three classes: small EVs (exosomes), large EVs (microparticles), and apoptotic bodies. Platelet-derived EVs (PEVs) are the most abundant class in human blood and can actively participate in numerous physiological and pathological processes. The information about the role of platelet exosomes in cardiovascular disease and the effect of antiplatelet agents on their release and content is very limited.

This is a multicenter prospective collection of data with diagnostic procedures different from standard clinical care in a specific cohort of patients, aimed to evaluate cardiovascular risk stratification with the European Society of Cardiology (ESC)/European Association for the Study of Diabetes (EASD) guidelines and "The Steno Type 1 Risk Engine" algorithm. The correlation between CVD risk, atherosclerosis, and microvascular complications of diabetes (retinopathy, nephropathy, and neuropathy) will then be evaluated, and the impact of glycemic variability and other glucose metrics on vascular damage will be characterized. The investigators plan to enroll at least 200 consecutive type 1 diabetes mellitus (T1DM) patients who meet all the inclusion criteria and none of exclusion criteria.