Clinical trial NCT06446271: Biomarkers in SCOTland CardiomyopatHy Registry (Bio-SCOTCH)
Official title: Biomarkers in SCOTland CardiomyopatHy Registry
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Cardiomyopathies
Genetic Predisposition
Cardiomyopathy, Primary
Keywords: Cardiomyopathy
Genetic
Biomarkers
Lead sponsor: NHS Greater Glasgow and Clyde
Sponsor class: OTHER
Collaborators: name: University of Glasgow
name: Roche Diagnostics GmbH
First posted: 2024-06-06
Enrollment: 750
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: People with a personal or family history of TTN, LMNA, MYBPC3, DSP, or FLNC gene variant who have been referred to the West of Scotland Inherited Cardiac Conditions Service clinic.

Brief summary: Genetic cardiomyopathy is increasingly recognised and can lead to heart failure, arrhythmia and sudden cardiac death. Some gene positive patients have rapidly progressive disease with high rates of heart failure and cardiac transplantation, while others present with SCD. Other gene positive patients will never develop cardiomyopathy. At present, we cannot distinguish between these groups and rely on expensive and labour-intensive surveillance by electrocardiography, echocardiography and sometimes cardiac magnetic resonance imaging.

This study will investigate existing and novel biomarkers (including blood, urine electrocardiographic and imaging) at various stages of disease in patients with a personal or family history of TTN, MYBPC3, LMNA, FLNC or DSP gene variant, which are known to cause cardiomyopathy.

Detailed description: There is a growing appreciation for the role that genetics play in the development of cardiomyopathy, which can lead to heart failure, arrhythmia and sudden cardiac death.

Increased use of genetic testing has identified numerous gene variants, which cause cardiomyopathy with dilated, hypertrophic, restrictive, non-dilated left ventricular and arrhythmogenic right ventricular phenotypes described.

Some gene variants cause a rapidly progressive cardiomyopathy with high rates of heart failure and cardiac transplantation, while others present with SCD, meaning that genotype-specific risk stratification and clinical surveillance is urgently needed. Some gene-positive individuals will never develop cardiomyopathy due to variable penetrance. At present, we cannot distinguish between these patients and therefore rely on expensive and labour-intensive surveillance by electrocardiography, echocardiography and sometimes cardiac magnetic resonance imaging. For every gene-positive affected individual with cardiomyopathy, cascade genetic testing will identify other gene-positive family members who are often asymptomatic and may not yet be affected.

A blood or urine-based biomarker that identifies pre-clinical disease or cardiomyopathy would allow for more efficient monitoring of gene positive people and could replace multiple, repeated electrocardiograms, echocardiograms and cardiac magnetic resonance imaging scans. A biomarker that accurately identifies pre-clinical cardiomyopathy could enable targeted early treatment. A biomarker that predicts future disease progression would be of high clinical value.

Eligibility criteria: Inclusion Criteria:

* Male or female ≥10 years of age
* Written informed consent / assent
* Pathogenic or likely pathogenic variant in a cardiomyopathy gene (TTN, LMNA, MYBPC3, DSP, FLNC) or undergoing predictive genetic testing (if negative these people would be invited to enter the control arm)

Exclusion Criteria:

* Unable to consent.
* Geographical / social reasons preventing attending study centre
* Unable to complete study assessments.
* Severe non-cardiac disease expected to reduce life expectancy \< 5 years
* Current participation in a blinded drug interventional trial (or treatment within 4 weeks)

Primary outcomes:
measure: Biomarker performance
timeFrame: 3 years
Secondary outcomes:
measure: Biomarker correlation
timeFrame: 3 years
measure: Prediction of cardiomyopathy development
timeFrame: 3 years with long-term data linkage
measure: Prediction of cardiomyopathy progression
timeFrame: 3 years with long-term data linkage
measure: Natural history of genetic cardiomyopathies
timeFrame: 3 years with long-term data linkage
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital
Study officials:
References: