Active clinical trials for "Cardiomyopathy, Dilated"

The goal of this protocol is to obtain information from individuals with cardiomyopathy and from their families in order to elucidate the molecular genetics of this disorder. This will provide the basis for future genetic counseling as well as contribute to elucidating the biology of normal and abnormal cardiac function.

The ICD-Reality study is a non-commercial, investigator-led, multicenter, prospective, randomized, controlled trial. We aim to determine the effect of CRT-D or CRT-P implantation in non-ischemic cardiomyopathy and heart failure patients. The reason why we initiated this trial is the lack of evidence-based treatment for the significant number of these patients. In these patients, 5-year mortality remains as high as 20% despite recent therapeutic advances. Based on currently available evidence, because of a significant decrease in mortality due to modern pharmacotherapy, it is not certain which of these patients should receive a CRT-P and who should receive a CRT-D. No dedicated and adequately powered trial has addressed this important question. We hypothesize that patients with symptomatic HF, LVEF ≤35%, without left ventricular mid-wall fibrosis on LGE-CMR, will not benefit from CRT-D implantation compared with CRT-P only implantation. If our hypothesis is confirmed, this could provide evidence for the management of these patients with a significant impact on common daily praxis and health care expenditures. We aim to enroll 600 patients in the trial. 924 patients are needed to be screened for these 600 patients to be randomized. Patients with non-ischemic HF visiting an out-patient department and possibly eligible for the trial will have their pharmacotherapy optimized. Patients with a significant amount of fibrosis will be excluded from the study and treated according to local practice with an emphasis on ICD implantation to prevent SCD. After fulfilling all eligibility criteria, including maximally tolerated pharmacotherapy, subjects will be randomized by the physicians who enrolled them in a 1:1 ratio to receive CRT-D or CRT-P implantation. All patients will be followed-up for at least 3 years after the implantation.

Heart failure (HF) is the most common nosology encountered in clinical practice. Its incidence and prevalence increase exponentially with increasing age and it is associated with the increased mortality, more frequent hospitalization and decreased quality of life. An initial approach to the treatment of HF patients with reduced left ventricular (LV) systolic function and left bundle branch block (LBBB) was implantation of device for cardiac resynchronization therapy using biventricular pacing. This has resulted in long-term clinical benefits such as improved quality of life, increased functional capacity, reduced HF hospitalizations and overall mortality. However, conventional cardiac resynchronization therapy (CRT) is effective in only 70% of patients. And the remaining 30% of patients are non-responders to conventional CRT. Cardiac conduction system pacing is currently a promising technique for these patients. Particularly, His bundle pacing (HBP) has been developed to achieve the same results. According to other studies HBP has shown greater improvement in hemodynamic parameters comparing with conventional biventricular CRT. But, nevertheless, there are significant clinical troubles with HBP, especially high pacing threshold. In this regard, in 2017, the left bundle branch pacing (LBBP) was developed, which demonstrated clinical advantages compared to conventional biventricular CRT. Also, since 2019, left bundle branch pacing-optimized CRT (LBBPO CRT) has been used in clinical practice. These methods have become an alternative to HBP due to the stimulation of LBB outside the blocking site, a stable pacing threshold and a narrow QRS complex duration on electrocardiogram. A series of case reports and observational studies have demonstrated the efficacy and safety of LBBP and LBBPO CRT in patients with CRT indications. However, it is not enough data about impact of CRT with LBBP and combined CRT with LBBP and LV pacing on myocardial remodeling, reducing mortality and complications. According to our hypothesis, CRT with LBBP and combined CRT with LBBP and LV pacing compared with conventional biventricular pacing will significantly improve the clinical outcomes and reverse myocardial remodeling in patients who are non-responders to biventricular CRT with HF, reduced LV ejection fraction and with indications to CRT devices with defibrillator function (CRT-D) or one of the CRT-D leads replacement.

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.

Mutations in the LMNA gene, which codes for lamins A and C, proteins of the nuclear lamina, are responsible for a wide spectrum of pathologies, including a group specifically affecting striated skeletal and cardiac muscles, with cardiac involvement being life-threatening. At the skeletal muscle level, a wide phenotypic spectrum has been described, ranging from severe forms of congenital muscular dystrophy to less severe forms of limb-girdle muscular dystrophy. The great clinical variability of striated muscle laminopathies, both inter- and intra-familial, can be observed in the age of onset, severity of signs and progression of muscle and heart involvement. To date, more than 400 LMNA mutations have been associated with striated muscle laminopathies (www.umd.be/LMNA/), highlighting strong clinical and genetic heterogeneity. A few recurrent mutations linked to a difference in severity have been identified. However, these genotype-phenotype relationships and the rare cases of digenism reported do not explain all the clinical variability of laminopathies. Therefore, there are probably other factors of severity than the causative mutation, called "modifier genes". Identification of such modifier genes has been initiated by studying a large family with significant clinical variability in the age of onset of muscle signs. A segregation analysis within this family identified 2 potential modifier loci. High-throughput sequencing restricted to these 2 regions according to phenotypic subgroups did not led to meaningful results so far. In addition, an international retrospective study of the natural history of early muscle laminopathies has allowed the investigators to highlight a strong inter-family clinical variability in patients carrying recurrent mutations. The investigators thus have strong preliminary data that could allow them to identify modifying genetic factors in a cohort of patients carrying a mutation in the LMNA gene. In order to identify these factors that modulate the clinical severity of laminopathies, the investigators wish to collect biological material (muscle and/or skin biopsies) from patients carrying a mutation in the LMNA gene. The study of this biological material using multi OMICs technics will allow the investigators to identify and functionally validate the action of these modifying genes. OMIICs is a set of techniques for characterising biological molecules using high-throughput approaches such as DNA sequencing, RNA sequencing and/or chromatin conformation (ATACseq...), proteins.

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.

The DZHK TranslatiOnal Registry for CardiomyopatHies (DZHK TORCH) represents a unique resource of clinical data and high quality biological samples to enable innovative clinical and molecular studies on cardiomyopathies (CMP). As a multi-center German cardiomyopathy registry, TORCH has been prospectively admitting patients since December 2014. 2,300 patients were recruited as planned. Taken together, patient data showed that the prevalence of these diseases is much higher in men than in women, atrial fibrillation is common in all forms of CMPs as well as rare forms of disease indicate a higher risk and higher morbidity. This DZHK TORCH register is now to be expanded with a second phase (DZHK TORCH-Plus). The second phase DZHK TORCH-Plus consists of 4 main modules: 1. "Clinical phenotyping, follow-up & biosampling" 2. "Genomics", 3. "Inflammation" and 4. "Biomarker". The central aims are 1) to significantly increase the number of probands (n = 4340) in order to better address the different types of CMPs, especially patients with rare CMP forms such as LVNC and ARVC or with probably molecularly explainable cardiomyopathies (familial DCM), 2) to prolong the longitudinal with a further follow-up to achieve sufficient events and thereby derive clinical recommendations for risk assessment, 3) to increase the number of probands with state-of-the-art phenotyping, 4) to pinpoint the effect of myocardial inflammation, fibrosis, gender and to determine or predict genotypes based for outcome, 5) to validate novel biomarkers developed in other DZHK studies, and 6) to foster active cooperation with international CMP registries and partners from industry.

This study aims to identify and assess new CMR techniques that can improve current CMR protocols.

Advances in treatment have led to improved survival of patients with cancer, but have also increased morbidity and mortality due to cancer treatment side effects. Cardiotoxicity is one the most frequent side effect which may lead to premature morbidity and death among cancer survivors. The most concerning cardiovascular complications of cancer therapy is myocardial dysfunction, leading to heart failure, and fatal arrhythmias, especially those induced by QT-prolonging drugs. PROMETEY (PROspective Multidisciplinary obsErvational Trial of cardiotoxicity in patiEnts undergoing anticancer therapy) - is Russian multicenter observational study assessing cardiotoxicity and its clinical, biochemical and genetic factors in patients on cancer therapy. The objectives of the study are: to reveal prevalence of cardiotoxic effects of cancer therapy in routine clinical practice in Russian Federation, to assess contribution of these effects to mortality of patients on cancer therapy, to evaluate clinical and economic consequences of cardiotoxicity in patients with cancer, to develop an individualized model of cardiotoxicity risk factors based on clinical and laboratory parameters. Patients: 400 cancer patients with toxic cardiomyopathy and 100 patients with idiopathic or family dilated cardiomyopathy. Study duration: 60 months. All patients will undergo complex examination after signing informed consent form(ICF): physical exam, echocardiography with speckle tracking analysis, ambulatory 48-hours ECG monitoring, biochemistry, analysis of biomarkers of myocardial injury, fibrosis and inflammation. Primary endpoint: all-cause mortality, heart transplantation, cardioverter-defibrillator implantation, hospitalization with heart failure decompensation. Secondary endpoints: thromboembolism, fatal/ nonfatal myocardial infarction, stroke, sudden cardiac death, surgical therapy of heart failure or arrhythmias, cardiovascular death, all-cause mortality, heart transplantation, cardioverter-defibrillator implantation.

Heart failure (HF) is the most common nosology encountered in clinical practice. Its incidence and prevalence increase exponentially with increasing age and it is associated with increased mortality, more frequent hospitalization and decreased quality of life. An initial approach to the treatment of HF patients with reduced left ventricular (LV) systolic function and left bundle branch block (LBBB) was implantation of cardioresynchronization device using biventricular pacing. This has resulted in long-term clinical benefits such as improved quality of life, increased functional capacity, reduced HF hospitalizations and overall mortality. However, conventional cardiac resynchronization therapy (CRT) is effective in only 70% of patients. And the remaining 30% of patients are non-responders to conventional CRT. Subsequently, His bundle pacing (HBP) has been developed to achieve the same results. According to other studies HBP has showed greater improvement in hemodynamic parameters than with conventional biventricular CRT. But, nevertheless, there are significant clinical troubles with HBP. In this regard, in 2017, the left bundle branch pacing (LBBP) was developed, which demonstrated clinical advantages compared to biventricular CRT. This method has become an alternative to HBP due to the stimulation of LBB outside the blocking site, a stable pacing threshold and a narrow QRS duration. A series of case reports and observational studies have demonstrated the efficacy and safety of LBBP in patients with CRT indications. However, it is not enough data about CRT with LBBP effectiveness in LV remodeling, reducing mortality and complications. According to our hypothesis, CRT with LBBP compared with conventional biventricular CRT will significantly improve the clinical outcomes and reverse LV remodeling in patients with chronic HF with reduced LV ejection fraction and reduce the number of non-responders to conventional CRT.