The Deep Phenotype of Lamin A/C Cardiomyopathy

Study Overview
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Brief Summary
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This study seeks to discover clinically useful tests to improve the diagnosis of a rare and serious heart muscle disease caused by mutations in a gene called 'Lamin'. Patients born with lamin gene mutations have apparently healthy hearts initially, they begin experiencing symptoms in their twenties or thirties, and by age 45 the majority have undergone a heart transplant, experienced a major cardiac complication, or have died. Sudden heart rhythm abnormalities are a major cause of sudden death so earlier diagnosis can save lives by enabling timely treatment or implantation of specialised pacemakers (defibrillators). In clinical practice, diagnosis of lamin heart disease currently relies on the genetic test. Very little is known about the detailed imaging features of the hearts of patients with lamin heart disease although advanced echocardiography and cardiac MRI now offer the opportunity to study the health of the heart without the need for radiation.

Detailed Description
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Research participants will undergo resting 12-lead ECG, 24-hour ambulatory ECG, baseline echocardiography, exercise echocardiography, cardiac MRI scan. Blood samples will be collected in all participants from both centers for immediate laboratory testing. Blood and urine samples will be collected in all participants and used for metabolomic, proteomic and lipidomic profiling and for targeted metabolite and enzyme analysis. Blood samples will be collected in all participants for future gene code analysis (DNA / RNA).

Official Title
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The Deep Phenotype of Lamin A/C Cardiomyopathy - A Proof-of-principle Relax-omic Pipeline

Conditions
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Lamin A/C Gene Mutation, Dilated Cardiomyopathy, Familial

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: LMNA+ cases with pathogenic LMNA mutations for LMNA+ and heart myocardial samples from the explanted hearts of LMNA+ patients who are scheduled to undergo clinically indicated heart transplantation at the Papworth Hospital NHS Trust. DCMWT cases: patients with heart muscle failure but with wild-type lamin gene. Heart myocardial samples from the explanted hearts of DCMWT patients who are scheduled to undergo clinically indicated heart transplantation at the Papworth Hospital NHS Trust. HV (controls): matched to cases. Exclusion Criteria: Needle-phobia that would preclude blood-letting Participants unwilling to consent Patients that have a conventional contraindication for cardiac magnetic resonance imaging (MRI). Patients that have had a blood transfusion within the last month and patients having haemodialysis will be excluded.

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Lamin DCM (LMNA+)<br>Adults with known pathogenic lamin (LMNA+) gene mutation. | |
| Wild types DCM (DCMwt)<br>Adults with heart muscle failure but normal (wild-type) LMNA gene (DCMwt). | |
| Healthy Volunteers (HV)<br>Matched healthy volunteers (HV). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Positive and negative predictive value of imaging-omics test for diagnosing LMNA-related heart muscle disease. |  | 3-4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dilated Cardiomyopathy, Lamin A/C Cardiomyopathy, Heart failure