Cardiomyopathy, Dilated

The goal of this observational study is to develop a registry of Brazilian patients with hereditary cardiovascular diseases, combining clinical and genomic data. The main questions it aims to answer are: Which genes are most commonly affected? What is the frequency of these genetic alterations in our population? Participants will be interviewed in routine medical care visits and their DNA will be sequenced.

Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by left ventricular or biventricular dilation and impaired contraction that is not explained by abnormal loading conditions.(1) Both inherited predisposition and environmental factors play an important part in the natural history of disease.(1) Cardiomyopathies are group of heart diseases that influence cardiac muscles directly and are not related to hypertension, congenital, valvular and pericardial diseases. The most common type of cardiomyopathy is dilated cardiomyopathy (DCM).(2) Definitions of DCM provided by two major professional organizations (American Heart Association (AHA) and European Society of Cardiology (ESC)) Both organizations agreed that DCM could be clinically defined by the presence of left ventricular dilation and contractile dysfunction in the absence of abnormal loading conditions and severe coronary artery disease.(3) Dilated cardiomyopathy usually manifests as chronic systolic heart failure, which is detected by echocardiography as impaired left ventricle fraction shortening less than 28%, with left ventricular end diastolic dimension Z-score\>2 ,leading to arrhythmias and sudden death.(4,5) idiopathic dilated cardiomyopathy (DCM) is characterized by dilatation and impaired contraction of the left ventricle or both ventricles, in the absence of underlying causes such as CAD, valve disease, congenital heart disease, or pericardial disease. Most patients present with symptoms of heart failure or arrhythmias, or even sudden cardiac death. An extensive family history (pedigree covering three or four generations), in combination with cardiological screening of first-degree relatives, results in a diagnosis of a familial form of DCM in up to 35% of cases.(11) In a multisite study in the USA and Canada, DCM was the most common form of cardiomyopathy among children (individuals of \<18 years of age):66% had idiopathic DCM, whereas of those with DCM due to known causes, 46% had myocarditis and 26% had neuromuscular disease. The annual incidence of DCM in children ranges from 0.18 to 0.73 per 100,000 person-years.(1) Oral PDE5 inhibitors, which primarily include sildenafil, vardenafil ,and tadalafil. Owing to its vasodilation effect and its impact on the endothelial function of blood vessels in the body, it is possible to use them to treat cardiovascular disorders such as pulmonary arterial hypertension and dilated cardiomyopathy. The use of PDE5 inhibitors in HF patients is backed by various theoretical evidence and clinical trials have begun to investigate their potential as an adjunct in the pharmacological management of HF.(6) PDE5 inhibition is an intriguing pharmacological strategy that enhances in vivo NO signaling by increasing the cyclic guanosine monophosphate (cGMP) availability. A number of theoretical backgrounds support the use of PDE5 inhibitors in HF, and several recent clinical studies have tested its clinical viability as a potential adjunct in the pharmacological management of HF.(7) In chronic heart failure improvement in exercise ventilation and aerobic efficiency with sildenafil is sustained and is significantly related with an endothelium-mediated attenuation of exercising muscle over signaling. Chronic sildenafil seems to be a remedy based on CHF pathophysiology and devoid of remarkable adverse effects.(8) Sildenafil is a specific inhibitor of type 5 phosphodiesterase (PDE5) that increases nitric oxide availability and nitric oxide-mediated vasodilation in CHF patients). Interest has therefore been focused on the potential of sildenafil to be beneficial in CHF. In acute studies, sildenafil increased myocardial contractility ,blunted adrenergic stimulation ,reduced left ventricular afterload), and improved lung diffusion capacity ,pulmonary hemodynamics at rest) and on exertion ,and exercise ventilation efficiency and aerobic performance.(8)

Dilated cardiomyopathy (DCM) is a common and serious heart disease characterized by left ventricular enlargement and impaired pumping function, with adverse prognosis (including heart failure, arrhythmia, heart-related hospitalization, and death) being a major concern for patients. Currently, a critical gap exists in accurately predicting which DCM patients are at high risk of these severe outcomes, limiting targeted clinical care. This observational, non-invasive study aims to develop and validate a clinical prediction model for early risk warning of adverse prognosis in DCM patients. The model integrates multi-parameter stress perfusion cardiac magnetic resonance (MP stress perfusion CMR)-a safe, high-resolution imaging technique that assesses cardiac structure, function, blood perfusion, and tissue damage under mild stress-and standard clinical data (e.g., age, gender, blood pressure, and routine heart test results). The model will be trained and tested using follow-up data from hundreds of DCM patients, with the analysis identifying patterns in CMR and clinical data associated with adverse outcomes. Once validated for accuracy, the model will provide doctors with personalized risk scores to prioritize care for high-risk patients (e.g., early intervention, close monitoring) and avoid over-treatment for lower-risk individuals. Beyond clinical application, the study will enhance understanding of DCM progression, laying the groundwork for improved diagnostic tools, more effective treatments, and better strategies to prevent DCM-related complications, ultimately improving patient quality of life and reducing mortality.

Arrhythmias are widespread among the global population. Although they can occur in healthy hearts, they are often the manifestation of a hereditary or acquired heart muscle disease, and may be the cause or, more often than not, the consequence. In recent decades, with advances in medical knowledge and technology, non-pharmacological therapies for arrhythmias have become increasingly popular. These fall into two broad categories: therapies aimed at electrostimulation and those aimed at ablation of arrhythmias. The selection of patients eligible for these procedures is essential for the effectiveness of the therapy, the reduction of complications and the optimisation of resources. Not all patients, even those selected according to guidelines, respond equally to the chosen therapy. Other patients, due to their clinical/ECG characteristics, do not have clear indications and remain in a borderline area where the class of evidence and/or recommendation of the guidelines is less stringent. Still others develop recurrences or complications during follow-up that require further intervention. In this context, it is essential in the study of these patients not only to use standard instrumental examinations, such as echocardiograms, Holter ECGs and stress tests (simple and cardiopulmonary), but also and above all to use advanced imaging methods (STE, 3D echo, MRI, CT, PET-CT) and remote monitoring tools that integrate diagnostic algorithms managed by artificial intelligence. In light of these considerations, our project consists of conducting an observational study that includes all patients with arrhythmias who are candidates for electrostimulation and/or ablation procedures at the Arrhythmology Unit and/or followed up at the Arrhythmology Clinic of our Polyclinic, in order to assess the clinical and/or imaging characteristics associated with a worse prognosis in this population, in terms of response to therapy and development of complications. Our main aim is to identify, within the above-mentioned population, the subgroups of responder patients versus non-responder patients, i.e. those with a worse prognosis , who deserve greater attention and more frequent follow-up.

Prospective, multicenter, randomized, placebo-controlled, double-blind clinical trial to evaluate safety and efficacy of candesartan in the prevention of the development of Dilated Cardiomyopathy (DCM) in genetic carriers of a DCM-causing variant without disease expression (asymptomatic)

One third of patients diagnosed with heart failure demonstrate left ventricular reverse remodelling and recovery of cardiac function following a period of medical therapy. The TRED-HF trial investigated the impact of therapy withdrawal in this cohort and found that 40% of patients relapsed within 6 months of stopping treatment. In this follow-on study, the investigators will investigate the safety of therapy withdrawal of sodium cotransporter 2 inhibitors (SGLT2i) and mineralocorticord receptor anatagonists (MRAs) in patients with a previous diagnosis of heart failure and recovered cardiac function, in a randomised controlled trial to assess whether this maintains remission in this population.

Although several studies have demonstrated beneficial effects of stem cell therapy in patients with non-ischemic dilated cardiomyopathy, the long term benefits and predictors of response to therapy remain undefined. The aim of this registry is to pool long-term clinical data in patients with non-ischemic dilated cardiomyopathy undergoing autologous cell therapy in an attempt to better define predictors of response to such treatment.