View clinical trials related to Cardiomyopathy, Familial.
Filter by:Sudden cardiac death (SCD) due to recurrent ventricular tachycardia (VT) is an important clinical sequela in patients with structural heart disease. VT generally occurs as a result of electrical re-entry in the presence of arrhythmogenic substrate (scar). Scar tissue forms due to an ischemic cardiomyopathy (ICM) from prior coronary obstructive disease or a non-ischemic cardiomyopathy (NICM) from an inflammatory or genetic disease. AADs can reduce VT recurrence, but have significant limitations in treatment of VT. For example, amiodarone has high rates of side effects/toxicities and a finite effective usage before recurrence. ICDs prevent cardiac arrest and sudden death from VT, but do not stop VT occurring. Recurrent VT and ICD therapies decrease QOL, increase hospital visits, mortality, morbidity and risk of death. Improvement in techniques for mapping and ablation of VT have made CA an alternative. Currently, there is limited evidence to guide clinicians either toward AAD therapy or CA in patients with NICM. This data shows significant benefit of CA over medical therapy in terms of VT free survival, survival free of VT storm and VT burden. Observational studies suggest that CA is effective in eliminating VT in NICM patients who have failed AADs, resulting in reduction of VT burden and AAD use over long term follow up. Furthermore, there is limited data on the efficacy of CA in early ICM with VT, or advanced ICM with VT. RCT data is almost exclusively on patients with modest ICM with VT, and this is not representative of the real-world scenario of patients with structural heart disease presenting with VT. Therefore the primary objective is to determine in all patients with structural heart disease and spontaneous or inducible VT, if catheter ablation compared to standard medical therapy with anti-arrhythmic drugs results in a reduction of a composite endpoint of recurrent VT, VT storm and death at a median follow up of 18 months.
Background A specific mutation in phospholamban (the PLN R14del mutation), has its origin in the northern parts of the Netherlands (Figure) and causes a severe lethal dilated and/or an arrhythmogenic cardiomyopathy. A large proportion of the population of Groningen (1:1000) carries this mutation. Until now, there is no specific treatment available for patients with PLN cardiomyopathy. Patients are treated like any other type of heart failure patients, although PLN cardiomyopathy has a different etiology from "usual" heart failure. Treatment is therefore insufficient; malignant ventricular arrhythmias and end-stage heart failure at a young age are very prevalent. To develop treatment options, the investigators aim to study the following knowledge gaps: - Pathophysiology. The clinical phenotype of PLN R14del cardiomyopathy bears characteristics of both arrhythmogenic and dilated cardiomyopathy (ACM and DCM). Using an "omics" approach of plasma, cardiac and skeletal muscle of patients and controls, the investigators aim to reveal distinct pathways affected by the mutant PLN, unique to the PLN R14del cardiomyopathy. This will be related to clinical data and mutant PLN expression levels in both cardiac and skeletal muscle biopsies. Using this extensive profiling, the investigators aim to identify disease mechanisms and provide the context for future risk stratification and disease progression monitoring. - Penetrance. Subjects with a heterozygous PLN R14del mutation show a wide variety in phenotype. Within the same family, patients can present either with over heart failure in their 20's or completely asymptomatic until at least their 70's. So far, no modifiers have been identified. The investigators will study cardiomyocytes derived from induced pluripotent stem cells from patients who are severely affected versus family members who are unaffected but carry the mutation. - Treatment response. The investigators have identified potential treatments, and confirmed their efficacy in in vivo models of PLN cardiomyopathy. To establish their efficacy in a human setting, the investigators will generate 3D cardiac tissues of cardiomyocytes gathered from induced pluripotent stem cells of patients affected in varying degrees and subject these tissues to the treatment. Methods: For the above purposes, the investigators will collect and analyze the following data/materials: - Serum and plasma of 90 PLN R14del carriers: 30 unaffected, 30 early affected and 30 end stage. - Skin biopsy of 20 PLN R14del carriers: 10 unaffected, 10 end stage. - Cardiac muscle biopsy (obtained during left ventricular assist device [LVAD]/ heart transplant [HTx] surgery) of 30 patients: 10 R14del, 10 arrhythmogenic cardiomyopathy, 10 dilating cardiomyopathy. - Skeletal muscle biopsy of 10 patients: 5 R14del, 5 non R14del family members
Interventional, cross-sectional biomedical study of children with genetic cardiomyopathy and healthy children. The aim is to generate, via induced human pluripotent stem cells (hiPSC), "patient-specific" cardiomyocytes (CMs) (hiPSC-CMs) to study the molecular mechanisms of cardiomyopathies of genetic origin.