Clinical Research Directory

HCMR Re-Imaging Study

This study aims to learn what might predict heart problems (like sudden death from a fast heart rhythm or heart failure) in people with a genetic condition called hypertrophic cardiomyopathy (HCM). HCM causes the heart muscle to become thick, which can make the heart stiff and harder to work properly. It can also affect the heart's electrical system. This study is looking to enroll patients that were previously part of a research project called "HCMR - Novel Predictors of Outcome in Hypertrophic Cardiomyopathy." The results of that study are still being reviewed, but they might show that people who had a substance called Gadolinium (MRI contrast or dye) collected in their heart muscle may have a higher risk for heart problems, including sudden cardiac death. This is called "late gadolinium enhancement" (LGE). This study is aiming to do follow-up imaging on those patients to better understand how LGE affects people with HCM.

COLLIGO-HCM: A Multinational Observational Study of the Real-World Effectiveness of Mavacamten Among Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM)

COLLIGO-HCM is a global observational study that will conduct observational research of hypertrophic cardiomyopathy (HCM) treatment in real-world clinical practice.

Aficamten and Patient-Reported Outcomes in Real-World nHCM

This multicenter, prospective, observational, real-world clinical study aims to evaluate the efficacy and safety of Aficamten in patients with symptomatic non-obstructive hypertrophic cardiomyopathy (nHCM) by prospectively observing changes in symptoms, biomarkers, imaging findings, and adverse reactions, etc. It will also record the dosing regimens at which individual patients achieve steady state, and explore the treatment patterns of Aficamten in Chinese patients with symptomatic nHCM.

Individualized Exercise Training in Hypertrophic Cardiomyopathy

Exercise intervention trials in patients with hypertrophic cardiomyopathy (HCM) have demonstrated an association with improvement in resting and exercise hemodynamics, ventricular remodeling, and anxiety/depression. However, no randomized controlled trials (RCTs) to date have assessed the effects of exercise intervention in patients with HCM on cardiac myosin inhibitors (CMIs). This trial aims to evaluate the efficacy of a 12-week individualized exercise training program in HCM patients receiving aficamten.

The Therapeutic Value of Mavacamten in Hypertrophic Cardiomyopathy With Mid-to-Apical Left Ventricular Obstruction

This study is a prospective interventional cohort study aimed at evaluating the therapeutic efficacy and clinical utility of Mavacamten-a targeted myosin inhibitor specifically developed for obstructive hypertrophic cardiomyopathy (HCM)-in patients with HCM characterized by mid-to-apical left ventricular obstruction.

A Real-World Study on Hypertrophic Cardiomyopathy in Chinese Population

This study is a prospective cohort study aimed at exploring the baseline characteristics and treatment patterns of the Chinese population with hypertrophic cardiomyopathy (HCM) in real-world settings. The objective is to assess the real-world treatment approaches and longitudinal outcomes in this population.

Mechanisms of Atrial Pathoelectrophysiology in HCM

This study aims to learn why atrial fibrillation (AF), a type of irregular heartbeat, happens more often and is harder to treat in people with hypertrophic cardiomyopathy (HCM). HCM is an inherited condition where the heart muscle is thicker than usual. Researchers will study electrical signals from the heart and advanced heart imaging. By doing this, they hope to better understand how AF behaves in people with HCM and why treatments may not work as well for them. The information from this study may help improve future treatments for people who have both HCM and AF.

Radiomics Analysis of CMR Imaging for Arrhythmic Risk Prediction in Hypertrophic Cardiomyopathy, With Longitudinal Risk Reassessment After Mavacamten Therapy in Obstructive Patients

Hypertrophic cardiomyopathy (HCM) is one of the leading causes of sudden cardiac death (SCD), particularly in young and middle-aged individuals. Current arrhythmic risk stratification mainly relies on clinical and imaging-based models, including the ESC HCM Risk-SCD score and guideline-recommended risk markers. However, these approaches show only moderate predictive accuracy at the individual level, highlighting the need for novel biomarkers able to improve risk prediction. Cardiac magnetic resonance (CMR) plays a central role in phenotypic characterization and prognostic assessment of HCM, particularly through the evaluation of late gadolinium enhancement (LGE), a marker of myocardial fibrosis. Recent studies suggest that radiomic analysis of LGE images can identify quantitative features of myocardial scar heterogeneity that provide additional prognostic information beyond conventional fibrosis burden assessment. Radiomics applied to pre-contrast cine CMR sequences may also capture quantitative features related to myocardial shape, texture, and contractile dynamics, potentially associated with myocardial disarray, mechanical alterations, and electromechanical instability. Integration of CMR radiomics with genetic data may allow a more comprehensive characterization of the arrhythmic substrate in HCM. In obstructive hypertrophic cardiomyopathy (oHCM), left ventricular outflow tract obstruction is a major determinant of symptoms and prognosis. Mavacamten, a selective cardiac myosin inhibitor, has been shown to significantly reduce LVOT gradient and improve symptoms and cardiac remodeling. However, it remains unknown whether CMR radiomics can detect phenotypic changes associated with mavacamten treatment and whether these changes may contribute to dynamic reassessment of arrhythmic risk.

Aom0304 in Adult Patients With Symptomatic Hypertrophic Cardiomyopathy

The goal of this clinical trial is designed to characterise the safety, tolerability, efficacy, and PK of Aom0304 across oHCM and nHCM populations and to inform dose selection for future Phase 3 development. The main questions it aims to answer are: 1. Which dose is safe and tolerant of Aom0304 in participants with HCM? 2. Which dose is effective of 12 weeks of Aom0304 treatment in participants with oHCM or nHCM? Researchers will compare different doses of Aom0304 to see which works best. All participants will receive Aom0304, but at different dose levels depending on which cohort they joined. Participants will: 1. Undergo screening up to 28 days before enrollment to confirm eligibility 2. Adjust dose every 2 weeks assessed by the Investigator according to predefined criteria at Titration Phase (Week 1 Day 1 to Week 8). 3. Continuation of the last tolerated and effective dose; no further escalation is permitted at Maintenance Phase (Week 8 to Week 12). 4. Study drug discontinued and follow up at Off-treatment Follow-up Period (at the end of Week 12 to Week 16).

LA-HCM Study : Rivaroxaban for Antithrombotic Prevention in Hypertrophic Cardiomyopathy Patients With Abnormal Left Atrial Strain.

Hypertrophic cardiomyopathy (HCM) is a common (\> 1/500 in the general adult population) genetically transmitted disease impacting markedly patients' lives from the early ages to the latest. The phenotype as the prognosis of HCM may greatly differ from one patient to another: most patients present no or few symptoms and a near-normal lifespan, while others are severely symptomatic. Paroxysmal, persistent or permanent atrial fibrillation (AF) is frequent in HCM, occurring in more than 20%-25% of patients and is often considered as an important turning point for the quality of life of these patients. AF decreases cardiac output and exercise tolerance, increases hospitalization rate, and markedly increase the risk of embolic stroke with the need for life-anticoagulation. It has been shown that stroke may precede AF discovery and that it may occur at young ages with devastation consequences. AF also may trigger sudden cardiac death. Observational studies have been conducted to search for parameters which correlate with the risk of AF (P wave duration and supra-ventricular burst on the Holter-ECG monitoring, L-wave morphology, degree of hypertrophy, clinical parameters-comorbidities, and size of the left atrium) with no real impact on clinical management. Left Atrial strain (LA-strain) has been recently demonstrated relevant (for instance our pilot work (for predicting stroke and/or AF (a cut-off of 15% is highly specific, 20% being the optimal cut-off). LA-strain (cut-off 20%) could be used for defining the patients that might require preventive anticoagulation therapy. A randomized clinical trial is needed to extend the use of anticoagulation therapy to patients in sinus rhythm but identified to be at risk for AF. Of note, it has been demonstrated that in this population, stroke occurred in 67% of the patients without any clinical atrial arrhythmia.

A Real-world HCM-cohort Trial

Hypertrophic cardiomyopathy (HCM) is a genetically mediated myocardial disease predominantly caused by pathogenic mutations in sarcomeric protein genes and characterized by asymmetric left ventricular hypertrophy. Patients with HCM commonly present with dyspnea, chest pain, and exercise intolerance. Sudden cardiac death, progressive heart failure, and thromboembolic events remain the leading causes of mortality and morbidity, substantially impairing quality of life and increasing healthcare burden. Despite advances in understanding the pathophysiology, diagnosis, and management of HCM, significant challenges persist, including etiological heterogeneity and underdiagnosis. At present, dedicated and systematic HCM databases remain lacking in China. Establishing a nationally HCM cohort and disease-specific database is therefore of considerable importance. In alignment with the goals of the "Healthy China 2030" initiative and supported by advances in medical big data technologies. This study aims to construct a comprehensive HCM cohort, evaluate contemporary diagnostic and therapeutic practices and patient prognosis, identify relevant risk factors, and ultimately improve the overall management of patients with HCM.

Mavacamten to Aficamten Transition in Patients With Obstructive Hypertrophic Cardiomyopathy

This is an investigator-initiated two-center study. The goal of this study is to investigate the feasibility, safety and efficacy outcomes of a seamless transition from mavacamten to aficamten in patients with obstructive hypertrophic cardiomyopathy (oHCM).

Multicentre Hypertrophic Cardiomyopathy Registry

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart condition, affecting approximately 1 in 500 people. It causes the heart muscle to thicken, which can lead to blockages in blood flow (left ventricular outflow tract obstruction), shortness of breath, and an increased risk of heart failure or sudden cardiac arrest. While standard treatments exist and new targeted medications (cardiac myosin inhibitors) have recently been approved, doctors still need better data to predict which treatments will work best for each individual patient. This national registry based in the UK is a secure database that collects health information from HCM patients across multiple NHS hospital sites in the UK over several years. Participants in this study will have their routine health information collected from their medical records, including details from heart scans (echocardiograms and MRIs), blood tests, and genetic information. With this HCM registry, we aim to improve disease understanding and risk prediction, paving the way for more personalised treatment plans for the HCM community in the future

Mavacamten in Adult Patients With Obstructive Hypertrophic Cardiomyopathy

This retrospective cohort study aims to evaluate the clinical efficacy and safety of mavacamten in adult patients with obstructive hypertrophic cardiomyopathy (oHCM). A total of 222 patients were included and categorized based on treatments received in routine clinical practice into a mavacamten group and a standard therapy group. The primary outcome is the change in resting left ventricular outflow tract (LVOT) gradient at Week 30. Secondary outcomes include changes in Valsalva LVOT gradient, New York Heart Association (NYHA) functional class, cardiac biomarkers, and echocardiographic parameters. Safety outcomes include adverse events and left ventricular systolic dysfunction. This study provides real-world evidence on the effectiveness and safety of mavacamten in Chinese patients with oHCM.

Perfusion Abnormalities in Hypertrophic Cardiomyopathy

The purpose of this study is to investigate whether myocardial microvascular perfusion in patients with hypertrophic cardiomyopathy improved after initiation of cardiac myosin inhibitor therapy.

Application of [68Ga]Ga-NI-FAPI-04 PET/CT Imaging in Fibroblast Activation Protein Related Diseases

The purpose of this study is to conduct clinical research on \[68Ga\] Ga-NI-FAPI-04 PET/CT imaging and further investigate its diagnostic value in fibroblast activation related diseases.

Retrospective Natural History Study of RASopathy-associated Cardiomyopathy (RAS-CM)

RASopathy-associated hypertrophic cardiomyopathy (RAS-CM) is a disease with high morbidity and high mortality if presenting during infancy. Targeted therapies have shown significant activity in preclinical models and case reports. Drugs that target the underlying cause of this disease are now developed in cancer patients. Conducting randomized trials is not possible in severely ill infants with RAS-CM. Existing historical controls from older eras are not sufficient as external controls to support drug development as they lack critical clinical and genetic information to allow comparison with the cohort planned for future clinical trials. The purpose of this investigator-initiated retrospective natural history study is to collect clinical information and genetic information in patients with RAS-CM. The first goal is to establish a data set that meets regulatory requirements for the use as external control data in a future clinical trial, composing non-randomized, single-arm, open-label study cohorts. The second goal is to obtain natural history information that supports the selection of secondary exploratory endpoints chosen in a clinical trial.

Precision Pharmacogenetics and Genotype Class Based Prediction of Mavacamten Response in Obstructive Hypertrophic Cardiomyopathy

This research study, aims to understand why a specific heart medication called mavacamten works better for some people with hypertrophic cardiomyopathy (HCM) than for others. We believe the answer might be in our genes. The study focuses on two key areas: 1. The specific gene causing HCM:The study will investigate whether the type of gene causing the condition in a person influences how well mavacamten works for them. 2. Each individual carry a certain gene that helps metabolise and process medication (otherwise known as pharmacogenetics). Our research will closely examine a gene called CYP2C19 to see if a person's natural processing speed (slow, normal, or fast) affects the medicine's performance. The study will also look for rare genetic variations that standard tests might miss.

One-stop Evaluation of Hypertrophic Cardiomyopathy in Cardiac Magnetic Resonance

This is a multi-center, observational study aiming to establish a precision diagnosis scheme and multi-dimensional risk prediction models for Hypertrophic Cardiomyopathy (HCM). The study plans to enroll 10000 adult HCM patients. It will integrate genetic testing, advanced cardiac imaging (echocardiography and cardiac magnetic resonance), and biomarker analysis to develop early diagnosis, differential diagnosis, and new risk prediction models for sudden cardiac death (SCD) and heart failure in HCM patients. Participants will undergo baseline assessments and be followed up every six months for up to 3 years to track clinical outcomes. This study is non-interventional and does not involve any investigational drugs or devices.

Multimodal Analysis of Endomyocardial Biopsies

The goal of this observational study is to pursue a multimodal approach to identify the molecular signatures and immune signalling molecules of various myocardial diseases and thereby contribute to improving diagnosis and therapy. The main aim is: -Identification of molecular profiles (e.g., proteome, lipidome, metabolome) and immune signalling profiles that are specifically associated with different myocardial diseases and the post-heart transplantation course. Participants already receiving an endomyocardial biopsy as part of their regular medical care will be enrolled. An additional biopsy sample will be taken for the above mentioned research.

The Application of T1 Mapping in Real-World

The goal of this observational study is to create a comprehensive real-world spectrum of T1 mapping measurements across different heart conditions. We aim to establish reference values for how heart tissue characteristics vary in various diseases, which will help doctors better interpret these advanced MRI measurements in clinical practice. The main questions it aims to answer are: What are the normal T1 mapping values for different heart diseases, and how do they compare to healthy hearts? Can we use the simpler "native T1" measurement (without contrast dye) instead of the more complex "ECV" measurement (which requires contrast dye) for diagnosis? Patients with various myocardial conditions will undergo CMR T1 mapping scans. We will analyze the MRI images and clinical records to establish disease-specific reference ranges for T1 mapping parameters, and validate the diagnostic accuracy of T1 mapping

Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias

Human induced pluripotent stem cells (hiPSCs) have driven a paradigm shift in the modeling of human disease; the ability to reprogram patient-specific cells holds the promise of an enhanced understanding of disease mechanisms and phenotypic variability, with applications in personalized predictive pharmacology/toxicology, cell therapy and regenerative medicine. This research will collect blood or skin biopsies from patients and healthy controls for the purpose of generating cell and tissue models of Mendelian heritable forms of heart disease focusing on cardiomyopathies, channelopathies and neuromuscular diseases. Cardiomyocytes derived from hiPSCs will provide a ready source of disease specific cells to study pathogenesis and therapeutics.

Myocardial Energetic Restoration in the Treatment of Obstructive Hypertrophic Cardiomyopathy

Hypertrophic Cardiomyopathy (HCM) is the most common inherited heart condition, where the heart muscles can thicken to the point of obstructing blood flow out of the heart. This condition is associated with a chronic state of energy loss in the heart muscle. Till more recently, a new class of medication (cardiac myosin inhibitors) have been introduced to directly target the heart muscle proteins (sarcomeres) to reduce the strength of contraction and relieve obstruction of blood flow out of the heart. While clinical trials have shown this class of medication significantly improves physical capacity and patient symptoms, it is still unclear, based on small scale published studies, where this improvement is achieved by restoring the fundamental energy balance within the heart. Our research study aims to answer this question and prove mechanistic insights of the use of this class of medication in the HCM population with blood flow obstruction (otherwise known as obstructive HCM) by using a specialised non-invasive MRI technique which accurately measures the heart energy score (specifically known as the PCr/ATP ratio) in each participant. Our objective is to determine how a patient with obstructive HCM have their energy scores affected, and improve over time with this medication therapy. If positive, this finding could establish the use of PCr/ATP ratio as a crucial, objective biomarker for monitoring therapeutic response and informing personalised dosing strategies for patient in the future.

ReGistry of hypeRtrophic cArDIomyopathy: Regional fEatures, geNeTics and Course

This study is envisioned as the very first of its kind in the Russian Federation, aiming to provide a comprehensive characterization of the clinical spectrum and disease burden, focusing on the epidemiology and progression of HCM in the largest cohort of adult and pediatric patients from this region. This registry will help increase knowledge of the epidemiology and prevalence of HCM, ultimately improving diagnosis and management. To assess the feasibility of new interventions, understanding the epidemiological profile of patients with HCM is essential. Clinical characteristics, imaging patterns, and outcomes may vary across different geographic regions. Completing this registry will enhance our understanding of the disease in Russia, and promote measures that modify the natural history of HCM