Clinical Research Directory

Use of Bone Marrow Derived Stem Cell and G-CSF With Circulatory Assistance in the Treatment of DCM

DCM Support is recruiting patients with dilated cardiomyopathy and heart failure symptoms. The goal of this clinical trial is to examine whether treatment with a patient's own stem cells can improve their heart function and alleviate heart failure symptoms. * Stem cells will be collected from bone marrow in the patient's hip under local anaesthetic. * The stem cells will be infused into the arteries that supply blood to the heart under local anaesthetic. * A mini heart pump will be used to take the strain off the heart during the procedure. * The follow-up involves a phone call at 1 month and clinic visits at 3 and 12 months

A Study of AZD4063 in PLN R14del Dilated Cardiomyopathy

The purpose of the study is to assess the safety, tolerability and the pharmacokinetics (PK) of AZD4063 after single and multiple dose administration in participants with phospholamban (PLN) R14del dilated cardiomyopathy.

Defining the Genetics, Biomarkers and Outcomes for Dilated Cardiomyopathy

Finding new ways to diagnose and treat Dilated Cardiomyopathy (DCM) could improve the health and well-being of patients with this condition. The main aim of this research study is to help develop better ways of diagnosing and treating patients with DCM. The information that is collected may help develop tailored treatments for patients with this disease in the future. This research study will recruit patients with DCM from a number of centres across England and follow their health over a period of years. Patients will give some blood samples for a type of genetic test called whole genome sequencing (WGS) to look for genetic changes. Patients will also have a magnetic resonance imaging (MRI) scan of their heart to look for any changes in the heart such as scarring, and check their heart function. The aim of this study is to discover if using WGS and MRI can improve the diagnosis of DCM. Another aim of the study is to look at how genetic changes and scarring in the heart may affect the progress of the disease. Studying patients with DCM may also help the investigators learn more about diagnosing and treating other diseases of the heart. The second aim of this study is to see whether using WGS and MRI scanning can also be useful in other types of heart diseases which might be affected by genetic changes or scarring in the heart.

Study of the Progression of Chronic Cardiovascular Conditions

This study will collect physiologic data in patients with cardiovascular conditions and observe the natural history of those conditions for research purposes.

Clinical Evaluation of the AccuCinch® Ventricular Restoration System in Patients Who Present With Symptomatic Heart Failure With Reduced Ejection Fraction (HFrEF): The CORCINCH-HF Study

Prospective, randomized, open-label, international, multi-center clinical study to evaluate the safety and efficacy of the AccuCinch Ventricular Restoration System in patients with heart failure and reduced ejection fraction (HFrEF).

A Phase 1 Open-Label Study of the Safety of Intravenous Allogeneic Neonatal Mesenchymal Cells (nMSCs) in Young Adult (1A) and Pediatric (1B) Patients With Dilated Cardiomyopathy (DCM)

This is a Phase 1 study to determine the safety and efficacy of allogeneic neonatal mesenchymal stromal cells (nMSCs) for the treatment of Dilated Cardiomyopathy. The purpose of the study is to help doctors and scientists learn if allogeneic neonatal mesenchymal stromal cells (nMSCs) infusions are a safe and effective way to improve cardiac function and left ventricular ejection fraction.

Pediatric Cardiomyopathy Mutation Analysis

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.

Absolute Coronary Flow in Patients With Heart Failure With Reduced Ejection Fraction and Left Bundle Branch Block With Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) is an effective therapeutic strategy in patients with symptomatic heart failure (HF) patients with LVEF of ≤35% and left bundle branch block (LBBB). However, approximately one-third of CRT-recipients do not improve after therapy (non-responders), despite meeting the required criteria. Previous studies have documented that the positive respons to CRT is related to the delayed electrical activation of the left ventricle in patients with LBBB. It has also been illustrated that non-ischemic CRT-candidates with LBBB demonstrate lower regional myocardial blood flow and metabolism in the septum. Additionally, it has been suggested that LBBB can lead to impaired coronary blood flow in the left anterior descending artery (LAD). This observation is based on an echocardiography-based study, that showed that the percentage of diastolic flow duration (%DD) in LAD was shorter in patients with LBBB compared to the control-group and patients with right-ventricular pacing. It has been demonstrated that CRT has positive effects on septal myocardial perfusion in patients with HF and LBBB. The dominant hypothesis explaining this phenomenon is built on improved septal myocardial work after CRT-implantation, which leads to increased myocardial energy and therefore increased myocardial perfusion. In contrast, it has been suggested that due to re-established synchronous left ventricular electrical activation, CRT reduces the septal intramyocardial pressure in early diastole, leading to a relatively longer antegrade flow duration in LAD. Therefore, the aim of the study is to evaluate the effect of CRT on coronary blood flow in LAD in patients with non-ischemic HF and LBBB. The investigators hypothesize that increased LV-function after CRT not only is due to resynchronized LV ejection and filling, but also improved coronary flow. The study aims to enroll 60 patients with heart failure due to non-ischemic dilated cardiomyopathy, LBBB, with or without CRT. All patients meeting the criteria will be recruited from the outpatient clinic at the Department of Cardiology, Aalborg University Hospital. Invasive flow measurements in the LAD, including fractional flow reserve (FFR), absolute coronary flow and -reserve will be conducted with the CRT on and off, respectively.

Dilated Cardiomyopathy-Cardiac Magnetic Resonance (DCM-CMR) Ancillary Study

The Dilated Cardiomyopathy-Cardiac Magnetic Resonance (DCM-CMR) Study is an ancillary study from the parent study, DCM Precision Medicine Study. The rationale for the DCM-CMR study is to leverage cardiac magnetic resonance (CMR) imaging to detect earliest findings of DCM in the at-risk family members enrolled into the parent study.

AI-Enabled Direct-from-ECG Ejection Fraction (EF) Severity Assessment Using COR ECG Wearable Monitor

This prospective, multicenter, cluster-randomized controlled study aims to evaluate the accuracy of an investigational artificial intelligence (AI) Software as a Medical Device (SaMD) designed to compute ejection fraction (EF) severity categories based on the American Society of Echocardiography's (ASE) 4-category scale. The software analyzes continuous ECG waveform data acquired by the FDA-cleared Peerbridge COR® ECG Wearable Monitor, an ambulatory patch device designed for use during daily activities. The AI software assists clinicians in cardiac evaluations by estimating EF severity, which reflects how well the heart pumps blood. In this study, EF severity determination will be made using 5-minute ECG recordings collected during a 15-minute resting period with participants seated upright. The results will be compared to EF severity obtained from an FDA-cleared, non-contrast transthoracic echocardiogram (TTE) predicate device. This comparison aims to validate the accuracy of the AI software.

Characterization of Patients With Cardiomyopathy to Identify Critical Patients Candidates for Cardiac Transplantation

The study aims to identify new diagnostic and prognostic markers for CMP that can help predict disease progression. In particular, the study will focus on microRNAs (miRNAs) and spatial transcriptomics, which are emerging techniques that may provide insights into the underlying disease mechanisms. By understanding these markers, the investigators hope to improve the way the investigators diagnose and manage CMP, particularly in terms of predicting progression to heart failure or heart transplantation. The study will evaluate patients with hypertrophic cardiomyopathy (e.g., sarcomeric forms, Anderson-Fabry disease, AL, and TTR cardiac amyloidosis), dilated cardiomyopathy and arrhythmogenic cardiomyopathy. These patients will undergo clinical evaluations, including ECG, echocardiograms, CMR, biopsy analysis, and genetic testing, as well as molecular studies such as transcriptomics and miRNA analysis. This comprehensive approach aims to identify potential new biomarkers for diagnosing and predicting the disease course.

Dilated Cardiomyopathy Detection Using AI and Screening With Mobile Technology (DCM-DETECT)

This is a prospective, single-arm clinical trial in which participants with dilated cardiomyopathy will invite their first degree relatives to undergo mobile cardiac, electrocardiogram screening.

Image-Based Prediction of Ventricular Tachycardia Events in Non-ischemic Cardiomyopathy

Risk stratification for sudden cardiac death (SCD) in patients with non-ischemic cardiomyopathy (NICM) remains suboptimal. Although current guidelines rely on severe left ventricular systolic dysfunction (left ventricular ejection fraction (LVEF) \< 35%) as key predictor of arrhythmic risk and clinical indication of prophylactic implantable cardioverter defibrillator (ICD), this approach seems inadequate, since registries report that only a minority of NICM ICD carriers experience an appropriate ICD shock during follow-up, whereas out-of-hospital cardiac arrests (OHCA) occur in patients with LVEF\>35% in up to 80% of cases. Moreover, pivotal primary prevention trials (DANISH trial, long-term outcome of the SCD-HeFT trial) failed to demonstrate a net mortality benefit of ICD in patients with NICM. As for most structural heart diseases (SHD), scar-related reentry has been addressed as the pathophysiological mechanism of ventricular arrhythmias (VAs) in patients with NICM, with fibrotic tissue being the substrate of this reentry. Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) is the gold standard for the non-invasive visualization and characterization of the myocardial fibrosis and according to retrospective studies is detected in nearly 30% of patients with NICM. In latest years, several studies and subsequent metanalyses have explored the correlation between CMR-detected LGE and occurrence of VAs, showing that presence, extent, location (septal vs lateral) and patten (focal vs multifocal vs ring-like) of non-ischemic fibrosis help in stratifying arrhythmic risk. Nonetheless, scar heterogeneity (that is, inherent composition of dense scars vs border zone (BZ), presence of strands of viable myocardium within the scar) has been indicated as a potential novel predictor of VAs. In a recent prospective multicenter registry on patients with class I indication for cardiac resynchronization therapy (CRT) (\>60% with NICM), not only scar mass, but even border zone (BZ) mass and presence of BZ channels were identified as independent predictors for VT occurrence in NICM patients. This BZ mass and BZ channels can be automatically identified using a commercially available, post-processing imaging platform named ADAS 3D LV (ADAS3D Medical SL, Barcelona, Spain), with FDA 510(k) Clearance and CE Mark approval. Thus, CMR-derived BZ mass might be used as an automatically reproducible criterium to reclassify those patients with NICM at highest risk for developing VAs/SCD in a relatively short period of at least 2 years. In the present cohort study, the investigators sought to: i) evaluate the usefulness of CMR-derived BZ mass measurement and identification of heterogeneous tissue channels (HTC) (among other scar characteristics derived from image post-processing) to predict the occurrence of VT events in an international, retrospective, multicenter, unselected series of patients with NICM without previous arrhythmia evidence (main study); ii) subsequently validate these predictors of VT occurrence in a prospectively-collected multicenter cohort study (substudy 1); iii) retrospectively evaluate in the subset of patients with \> 1 LGE-CMR performed as part of standard clinical practice if any change in BZ mass and HTC presence occurs over time and if this correlates with occurrence of VAs (substudy 2).

Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age

Dilated cardiomyopathy (DCM) is a condition associated with left and /or right ventricular (LV) dilatation and systolic dysfunction without coronary artery disease or abnormal loading circumstances proportionate to the severity of LV impairment. It is one of the leading causes of heart failure in younger adults. About 35% of patients have genetic mutations affecting cytoskeletal, sarcomere, and nuclear envelope proteins while others are idiopathic and possibly complications of myocarditis. Recently, in patients with peripartum cardiomyopathy (PPCM)-a subtype of dilated cardiomyopathy, high levels of prolactin and its degradation by-products including a cleaved 16kDa N-terminal fragment have emerged as key factors in the pathophysiology. The 16kDa prolactin induces profound endothelial damage and subsequent cardiomyocyte dysfunction and hence heart failure. Bromocriptine has been studied as a potential treatment option and placebo-controlled studies have demonstrated its beneficial role in women with Peripartal cardiomyopathy (PPCM). However, prolactin level may also increase during menstrual cycles of reproductive-age women, which candidates the use of bromocriptine in women of all reproductive ages. The aim of this study is therefore to assess the potential effect of bromocriptine in dilated cardiomyopathy among women of reproductive age.

A 10-Minute Cardiovascular Magnetic Resonance Protocol for Cardiac Disease

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

Outcome-targeted Therapy: Principle and Outcome Evaluation: Clinical Study and Phenotype-genotype Correlation

Brief Summary(Use lay language. Include a statement of the study hypothesis.): Dilated cardiomyopathy (DCM) is the most common childhood cardiomyopathy and is associated with significant early morbidity and mortality. Those who fail to improve within the first year of diagnosis usually deteriorated even upon aggressive anti-congestive medications. Investigators had conducted precision-medicine-based approach to provide strategic approach as drug repurposing to identify new treatments. Investigators have identified the beneficial effects from a statin, simvastatin, to restore the cardiac contractility in the human induced pluripotent stem cell lines derived from a DCM proband and the proband's father. The mutant mouse consequently confirmed the beneficial effects. The initial experience in the proband is promising. This clinical trial is to find out if simvastatin will benefit the cardiac function of DCM patients.

Myocardial Telomere Recapping Study for Dilated Cardiomyopathy

The aim of this study is to determine the safety and feasibility of giving an adeno-associated viral vector expressing a modified telomerase protein (TERT), driven by cardiac troponin T promoter (AAV9-cTnT-modTERT), to 12 dilated cardiomyopathic patients.

IntelliStent for Pulmonary Flow Adjustment in Congenital Heart Disease and Dilated Cardiomyopathy

IntelliStent is intended to achieve reduction of pulmonary hypertension, improvements in symptoms and quality of life in pediatric, adolescent and adult patients with congenital heart disease associated pulmonary arterial hypertension or left ventricular dilated cardiomyopathy.

The SMARTER Cardiomyopathy Study

Cardiomyopathies are diseases of the heart muscle. Known genetic factors may account for some cardiomyopathy cases but there is still much to understand about the genetic and environmental causes and how the disease progresses. Finding new ways to diagnose and treat cardiomyopathies could improve the health and well-being of patients with these conditions. This study will collect data from individuals with cardiomyopathy or related heart muscle disease, or with a possible genetic predisposition to cardiomyopathy, and follow them over time to observe the progress of their heart and health. This study will collect DNA, blood samples, and detailed clinical \& lifestyle information at the start of the study, and data collected during routine healthcare visits over time. * learn what causes cardiomyopathy, and therefore how to treat it * understand why cardiomyopathy progresses differently in different people, to improve the ability to recognise who will benefit from different treatments at different times The investigators will collaborate with other centres internationally to collect a large of group of participants with similar cardiomyopathies, providing power to identify new pathways that cause disease and ways of predicting which participants are at risk of having more severe disease.

The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus

Evaluating the efficacy of sirolimus (compared to standard therapy alone) in the treatment of dilated cardiomyopathy infected with Kaposi Sarcoma-associated virus -- a multicenter randomized controlled study.

Cardiac Magnetic Resonance for Risk Stratification in Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is an increasingly recognized cause of morbidity and mortality with heterogenous etiologies (eg, genetic, environment) and clinical manifestations, characterized by left ventricular (LV) systolic dysfunction and LV or biventricular dilation. Previous publications reported the three-year treated mortality rates remain high at 12%-20% and a reported 5-year mortality rate up to 50%, with death resulting from ventricular arrhythmia leading to sudden cardiac death (SCD) or advanced heart failure (HF). With large fields of view and high spatial resolution, Cardiac magnetic resonance (CMR) is the reference standard for assessing cardiac mass, volume, and function. CMR also provides non noninvasive characterization of the myocardium benefiting to differential diagnosis and risk stratification.

Cardiovascular Magnetic Resonance GUIDEd Insertion of Implantable Cardiac Defibrillator in Dilated CardioMyopathy

CMR GUIDE DCM is a randomized controlled trial with a registry for non-randomized patients. Patients enrolled will have non-ischemic cardiomyopathy (NICM) with mild to severe Left Ventricular (LV) systolic dysfunction with replacement fibrosis identified on Cardiac Magnetic Resonance (CMR). 954 patients will be randomised from 50 sites across 4-6 countries worldwide to receive an implantable defibrillator (ICD) or implantable loop recorder (ILR). Device and clinical follow-up will be performed at 3, 6, 12, 24, 36 months and at end of study.

Molecular and Imaging Studies of Cardiovascular Health and Disease

Biobank is a program which collects biological samples, health information and imaging data from consented patients and stored them at the core facility. These information would be used to study the molecular, imaging and outcome studies of cardiovascular health and disease.