Active clinical trials for "Cardiomyopathies"

Transthyretin is a protein produced in the liver that transports thyroid hormone and vitamin A. A single substitution of an amino acid in the structure of TTR can result in a relatively unstable protein, the breakdown products of which (predominantly monomers) aggregate abnormally and produce proteinaceous deposits in nerves and the heart. These deposits are known as amyloid and produce progressive nerve and heart damage. Amyloidosis due to a mutant TTR is usually an autosomal dominant and hence is a familial condition. Wild-type TTR is also capable of producing amyloid deposits which predominantly involves the heart (rather than the nervous system) resulting in a progressive decrease in cardiac function with increasing signs of heart failure. This study aims to determine whether subcutaneous injection of an antisense oligonucleotide drug, known as inotersen, that has been specifically designed to reduce production of the protein transthyretin by the liver, can slow or stop the progression of TTR amyloid cardiomyopathy as compared to historical controls, using advanced echocardiography and cardiac MRI. The study also aims to determine the tolerability and safety of this drug when administered over a 24-month period to patients with TTR amyloid cardiomyopathy.

Type 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for heart failure (HF). Whereas the prevalence of HF in the general population is 1-4%, it reaches approximately 12% in T2DM patients. In 1972, Rubler reported a specific diabetes-associated cardiac injury called diabetic cardiomyopathy. This cardiomyopathy is defined by ventricular dysfunction occurring without coronary disease or hypertension. Diabetic cardiomyopathy is also characterized by left ventricular (LV) hypertrophy, diastolic dysfunction and myocardial fibrosis. A large body of work indicates that diabetic cardiomyopathy is associated with altered cardiac energy metabolism. Indeed, in obese T2DM patients, heart lipid uptake is increased. Several studies support that free fatty acid (FFA) accumulation leads to the increased production of diacylglycerol (DAG), ceramides and reactive oxygen species (ROS), affecting cardiac insulin sensitivity and cardiac contractility. On the other hand, hyperglycemia and glucose overload have been involved in cardiac hypertrophy and dysfunction in the context of T2DM and obesity. The diabetic heart is simultaneously characterized by impaired insulin-stimulated glucose uptake and obvious signs of glucose overload, such as ROS and advanced glycation end-product (AGE) production as well as hexosamine pathway chronic activation. Interestingly, when comparing diabetic and nondiabetic obese patients, we previously demonstrated that hyperglycemia per se plays a central role in the impaired cardiac mitochondrial activity associated with myocardial contractile dysfunction.

Accumulated clinical and experimental data suggest that dysfunctional coronary microcirculation plays a pivotal role in the progression of heart failure despite an optimal therapy used. Therefore, we hypothesize that improvement in microvascular function by calcium antagonist, verapamil may result in additional clinical benefit. Thus, the aim of this study is to compare the effect of treatment with verapamil or carvedilol on long-term outcomes in stable, chronic heart failure secondary to non-ischemic cardiomyopathy.

Cardiac resynchronization therapy has been shown to be effective in reducing symptoms and mortality in heart failure patients. However, very few is known about the importance of the left ventricular pacing site. We study in a random order 11 different left ventricular pacing sites and compare their hemodynamics using pressure-volume catheters. The consequences on the surface ECG are also assessed.

The principal aim is to investigate the safety and efficacy of rosiglitazone in patients with chronic systolic heart (Dilated cardiomyopathy). We hypothesize that in patients with heart failure, rosiglitazone is safe, and can reduce nitric oxide (NO) derived oxidative stress (in particular, nitrotyrosine) thereby improving endothelial dysfunction, left ventricular performance, and metabolic parameters.

Randomized controlled parallel open-label study in people living with HIV and at least 6 month of treatment with dolutegravir/abacavir/lamivudine prior to inclusion. Participants (n=95) are randomized to continue 3 drug-regimen dolutegravir/abacavir/lamivudine (control) or switch to two-drug regimen with dolutegravir/lamivudine (intervention). Follow-up is 48 weeks. Data is collected at baseline and week 48. Primary outcome is changes in weight from baseline of more than 2 kg. Secondary outcomes are changes in cardiac risk, composition and calcification of the heart tissue, and changes in body composition and metabolism, inflammation and coagulation. A MRI substudy is applied to focus on the cardiac adverse effects of abacavir.

Chagas disease is considered by the World Health Organization (WHO) as one of the most neglected tropical diseases in the world, having relevance in many Latin America countries. In addition, it already affects North America, Europe, Asia and Oceania. Some studies suggest that chagasic heart failure has a worse prognosis, with up to 50% shorter survival than other etiologies. The PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Blocker-Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study showed 20% reduction in mortality comparing sacubitril/valsartan with the standard treatment with ACE (angiotensin converting enzyme) inhibitors. In the scenario of chagasic cardiomyopathy, a post hoc analysis of PARADGIM-HF was reported on 113 patients. Reduced risk of cardiovascular death or hospitalization for HF was noted in the group treated with sacubitril/valsartan. Attention was drawn the study's limitations that included the small number of patients and reduced statistical power. Therefore, the benefit of this new class remains uncertain in heart failure due to Chagas cardiomyopathy. The ANSWER-HF Trial will be a clinical, randomized, single-center, prospective, double-blind, controlled study. It will include 200 consecutive participants with Chagas cardiomyopathy and left ventricular ejection fraction less than 40% randomized independently. The objective of this study is to evaluate the benefit of sacubitril/valsartan compared with enalapril in patients with heart failure due to Chagas cardiomyopathy, with reduced ejection fraction. The primary endpoint of the study is the change of left ventricular ejection fraction determined by transthoracic echocardiography. Secondary endpoints include: assessment of ventricular arrhythmias; evaluation of functional class; assessment of functional capacity; assessment of ventricular remodeling; and evaluation of biomarkers. The patients will be followed for 6 months after treatment start. All patients will be undergone to Doppler Echocardiography, 24-hour Holter, 6-minute walk test, Biochemical and hematological exams and Biomarkers at the baseline and after 6 months.

A Study to evaluate the efficacy of psychotherapy for easing the cardiac symptoms and improving and quality of life in patients with hypertrophic cardiomyopathy accompanied with depression

The overall aim of the project is to test the feasibility and safety of allogeneic adipose-derived stromal cells (CSCC_ASC) investigational medicinal product, to improve myocardial function in patients with non-ischemic dilated cardiomyopathies (NIDCM) and heart failure.

The prevalence of valvular heart disease is on the rise along with the aging society and the generalization of echocardiography. Furthermore, the rheumatic valvular heart disease is much more prevalent in Asia than in Western countries, and the frequency of valve disease is higher in Asia. The effect of an implantable cardioverter defibrillator (ICD) in the primary prevention of sudden cardiac death in ischemic cardiomyopathy is well established and has become a standard of care. However, there is limited research on the effect of ICD implantation for primary prevention in patients with heart failure due to valvular heart disease. In a small study, the incidence of fatal cardiac arrhythmia was lower in patients with valvular cardiomyopathy (5%) who received ICD implantation for primary prevention than in those with ischemic cardiomyopathy. But there is also a report that the appropriate ICD treatment is not different from that of ischemic heart disease in valvular heart disease patients. Therefore, it is necessary to study the primary prevention effect of ICD on valvular cardiomyopathy in a larger number of patients. The purpose of this study was to investigate the effect of ICD on the prevention of sudden cardiac death in patients with heart failure due to valvular heart disease through prospective, multicenter, and observational studies.