Clinical Research Directory

BE.Amycon Biobank & Data Registry UZ Leuven

The goal of this study is to collect and store human body material (HBM) of patients with amyloidosis in a biobank "BE.Amycon biobank" for future research and to collect clinical data of patients with amyloidosis in a database "BE.Amycon data registry".

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.

ATTR Amyloid Cardiomyopathy: Characterization of Extracellular Vesicles as Potential Disease Stratifiers and Prognostic Biomarkers

This study explores whether extracellular vesicles (EVs) tiny particles released into the bloodstream by cells can serve as early and minimally invasive biomarkers for transthyretin amyloid cardiomyopathy (ATTR-CM). Because ATTR-CM is often diagnosed only after significant heart damage has occurred, there is an urgent need for earlier detection methods. The study will enroll individuals with different clinical presentations of transthyretin amyloidosis, along with healthy controls. Participants will undergo blood sampling, cardiac imaging (including echocardiography, cardiac MRI, and scintigraphy when indicated), and molecular EV analysis. By comparing EV profiles across groups, the study aims to determine whether these vesicles reflect early cardiac involvement, track disease progression, and support more accurate and timely diagnosis. Ultimately, this research seeks to improve clinical decision-making and patient outcomes in ATTR cardiomyopathy.

Multimodality Cardiac Imaging for Disease Progression in ATTR-CM

The goal of this clinical trial is to investigate whether new imaging techniques can help us to better understand the cardiac amyloidosis. The disease can be slowed down with various medications (e.g., tafamidis, acoramidis, or vutrisiran). However, treatment is not effective in all patients-in about one-third of cases, the disease continues to progress. So far, we know little about the exact causes of this and what biological changes occur in the heart muscle. The main question it aims to answer is: Will new imaging techniques help us understand the course of the cardiac amyloidosis? Participants will have additional examinations: * At the beginning of the study: one additional heart ultrasound examination, one cardiac MRI and one cardiac PET, blood examination during the regular examination, questionnaires. * After a year: one additional heart ultrasound examination, one cardiac MRI and one cardiac PET, blood examination during the regular examination. Time required: * Heart ultrasound examination: 5-10 Minutes * Cardiac MRI: 2 hours * Cardiac PET: 2 hours * Questionnaires: 5-10 Minutes.

Ultrasound Therapy In Cardiac Amyloidosis

This is a prospective pilot clinical study of subjects with cardiac amyloidosis and control subjects without amyloidosis where we plan to evaluate changes in myocardial blood flow, systolic and diastolic function before and after sonotherapy.

Essen Amyloidosis Registry

The Essen Amyloidosis Registry (EAR) is a prospective, observational registry designed to collect comprehensive clinical data on patients diagnosed with systemic amyloidosis. The registry aims to improve the understanding of disease progression, diagnostic pathways, and treatment outcomes. The registry is hosted at the University Hospital Essen and follows patients longitudinally. Inclusion is open to all patients with suspected or confirmed amyloidosis who provide informed consent.

Intracardiac Flow Assessment in Cardiac Amyloidosis

The primary objective of this study is to define the intracardiac flow imaging biomarkers in cardiac amyloidosis.

Subclinical Transthyretin Cardiac Amyloidosis in V122I TTR Carriers

Approximately 1.5 million of the 44 million Blacks in the United States are carriers of the valine-to-isoleucine substitution at position 122 (V122I) in the transthyretin (TTR) protein. Virtually exclusive to Blacks, this is the most common cause of hereditary cardiac amyloidosis (hATTR-CA) worldwide. hATTR-CA leads to worsening heart failure (HF) and premature death. Fortunately, new therapies that stabilize TTR improve morbidity and mortality in hATTR-CA, especially when prescribed early in the disease. However, hATTR-CA is often diagnosed at an advanced stage and conventional diagnostic tools lack diagnostic specificity to detect early disease. The overall objectives of this study are to determine the presence of subclinical hATTR-CA and to identify biomarkers that indicate amyloid progression in V122I TTR carriers. The central hypothesis of this proposal is that hATTR-CA has a long latency period that will be detected through subclinical amyloidosis imaging and biomarker phenotyping. The central hypothesis will be tested by pursuing 2 specific aims: Aim 1) determine the association of V122I TTR carrier status with CMRI evidence of amyloid infiltration; Sub-aim 1) determine the association of V122I TTR carrier status with cardiac reserve; Aim 2) determine the association between amyloid-specific biomarkers and V122I TTR carrier status; and Sub-aim 2) determine the association of amyloid-specific biomarkers with imaging-based parameters and evaluate their diagnostic utility for identifying subclinical hATTR-CA. In Aim 1, CMRI will be used to compare metrics associated with cardiac amyloid infiltration between a cohort of V122I TTR carriers without HF formed by cascade genetic testing and age-, sex-, and race-matched non-carrier controls. For Sub-Aim 1, a sub-sample of carriers and non-carrier controls enrolled in Aim 1 will undergo novel exercise CMRI to measure and compare cardiac systolic and diastolic reserve. Aim 2 involves measuring and comparing amyloid-specific biomarkers in V122I TTR carriers without HF with samples matched non-carriers (both from Aim 1) and individuals with symptomatic V122I hATTR-CA from our clinical sites. These biomarkers detect and quantify different processes of TTR amyloidogenesis and include circulating TTR, retinol binding protein 4, TTR kinetic stability, and misfolded TTR oligomers. Sub-aim 2 will establish the role of these biomarkers to detect imaging evidence of subclinical hATTR-CA disease.

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.

NatiOnal Referral cenTEr Study of Transthyretin Amyloid Cardiomyopathy(ATTR) Patients on Tafamidis

All ATTRwt patients on tafamidis 61 mg treatment will be clinically evaluated before treatment initiation and subsequently every six months for the eligibility to continue tafamidis treatment, according to Italian Medicines Agency regulations. C onsidering the significant risk of developing heart rhythm disturbances due to cardiac amyloidosis, especially in transthyretin form (ATTRwt), in routine clinical practice a stricter heart rhythm monitoring is recommended in ATTRwt patients. Moreover, particular attention is usually paid for those who present atrio-ventricular and/or intraventricular block at the baseline electrocardiogram. Data about rhythm disturbances and diuretic dose need will be collected during the planned physical examination every six months and the Holter ECG monitoring requested by the physician at the end of every planned clinical evaluation.

Cardiac Amyloidosis in HFpEF

Heart failure with preserved ejection fraction (HFpEF) accounts for half of heart failure cases with heterogenous cause and variable presentations. The diagnosis of HFpEF required clinical signs and symptoms of HF, normal left ventricular ejection fraction (LVEF) and evidence of diastolic dysfunction. No treatment has been shown in recent major clinical trials having benefits in these patients. One major reason of the poor response to medical treatment is the heterogeneity of HFpEF, which contains many different underline causes. To identify the underlying causes of HFpEF may improve the diagnosis and treatment in these patients. Age-related amyloid deposition has first been reported in 1876 and the following autopsy studies showed the prevalence of senile cardiac amyloid is up to 25%. Recently, it has been recognized that the deposits in senile cardiac amyloid are derived from wild-type transthyretin (TTR). Transthyretin amyloidosis cardiac amyloidosis (ATTR CA) is caused by myocardial deposition of misfolded transthyretin protein. There are 2 types of ATTR classified by genetic mutation including wild-type ATTR (ATTRwt) and familial cardiac amyloid caused by TTR mutation (ATTRm). Multimodality techniques have been developed to assist in the diagnosis of the diagnosis of TTR. Among them, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy is a non-invasive test and it can diagnose TTR from other cause diverse form of cardiac amyloidosis and cardiomyopathy. In the study of Gonzalez-Lopez et al, in 120 HFpEF patients, 16 (13.3%) had positive 99mTc-DPD scan. Four patients with positive 99mTc-DPD scan received endomyocardial biopsy and confirmed cardiac amyloid deposition. ATTRwt could be an important cause of HFpEF and it was often under diagnosed. A recent study in Spain reported that 13% of patents over age of 60 years with HFpEF and left ventricular wall thickness of 12mm or more had ATTRwt. However, the prevalence of ATTRwt among patients with HFpEF is not well-established in Taiwan and Asia. The aim of this study is to determine the prevalence, clinical characteristics, risk factors and outcomes of ATTRwt related HFpEF patients in Taiwan.