Genetic testing for AF-triggered cardiomyopathy
Genetic Susceptibility to AF-Induced Cardiomyopathy
We will test whether people who develop heart failure during atrial fibrillation carry specific disease-causing gene variants compared with people who have AF but do not weaken their heart.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 299 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Barts & The London NHS Trust Academic / other |
| Drugs / interventions | chemotherapy |
| Locations | 1 site (London) |
| Trial ID | NCT07574697 on ClinicalTrials.gov |
What this trial studies
This is an observational, case-controlled genetic study comparing a focused dilated cardiomyopathy gene panel across three groups: 92 patients whose left ventricular function fell during atrial fibrillation and then recovered after rhythm control (cases), 184 patients with AF who never developed reduced ejection fraction (negative controls), and 23 patients who developed heart failure and did not recover after AF treatment (positive comparators). DNA will be screened only for a limited set of clearly pathogenic variants to reduce uncertain results and cost. Genetic variant frequencies will be compared between groups to see if certain variants are enriched in AF-triggered cardiomyopathy. Clinical inclusion requires documentation of LVEF during rate-controlled AF and follow-up LVEF after catheter ablation or cardioversion to confirm recovery status.
Who should consider this trial
Good fit: Ideal candidates are adults with persistent atrial fibrillation who either developed reduced LVEF during AF that normalized after ablation or cardioversion (cases), adults with AF who maintained normal LVEF (negative controls), or adults who developed heart failure that did not recover after AF treatment (positive comparators).
Not a fit: People without AF, children, patients whose cardiomyopathy clearly has non-AF causes, or those who have not undergone rhythm-control treatment are unlikely to benefit directly from this study's findings.
Why it matters
Potential benefit: If successful, the findings could help clinicians identify AF patients at higher risk of heart muscle weakness and prioritize them for earlier rhythm-control interventions like catheter ablation to prevent or reverse heart failure.
How similar studies have performed: Targeted cardiomyopathy gene panels have identified pathogenic variants in other stress-triggered cardiomyopathies (for example pregnancy- or alcohol-related), but applying this focused genetic approach specifically to AF-triggered cardiomyopathy is relatively novel.
Eligibility criteria
Show full inclusion / exclusion criteria
INCLUSION: AIC (Cases): * Age ≥18 * Persistent AF before index catheter ablation or cardioversion * LVEF ≤40% during rate-controlled (resting HR \<100bpm, mean HR on 24-hour Holter \<100bpm) AF prior to index catheter ablation or cardioversion * LVEF normalisation (LVEF ≥55%) in SR, post-catheter ablation or cardioversion (≥3 months post-catheter ablation or cardioversion), no AF (\>30 seconds of continuous AF) detected outside blanking period (8 weeks post-catheter ablation), and with no new introduction of any new or increased dose of heart failure guideline-directed medical therapy (GDMT) (renin-angiotensin-aldosterone system inhibitors (RAASi), Sodium Glucose Co-transporter 2 (SLGT2) inhibitors, increased dose of beta-blocker (BB), mineralocorticoid receptor antagonist (MRA)) AF-pEF (Negative controls): * Age ≥18 * Persistent AF before index catheter ablation or cardioversion * LVEF ≥55% during rate-controlled (resting HR \<100bpm) AF. AIC-genotyping study, v1.7, 27.01.26 Page 13 of 28 AF/HF non-responders (Positive controls) * Age ≥18 * Persistent AF before index catheter ablation or cardioversion * LVEF ≤40% during rate-controlled (resting HR \<100bpm) AF before index catheter ablation or cardioversion. * Persistent LVSD (LVEF ≤40%) in SR, post-catheter ablation or cardioversion (≥3 months post-catheter ablation or cardioversion), no AF (\>30 seconds of continuous AF) detected outside blanking period (8 weeks post-catheter ablation) and with no change in heart failure GDMT (RAASi, SGLT2 inhibitors, increased dose of BB, MRA). EXCLUSION: AIC (Cases). * No alternative cause for LVSD (ischemic cardiomyopathy/non-ischaemic cardiomyopathy before AF diagnosis, primary valve disease, inherited cardiomyopathy * Any pregnancy during AF or in the 12 months preceding LVSD onset. * Alcohol intake \>21 units/week * Any history of cardiotoxic chemotherapy AF-pEF (Negative controls) * No known cause for LVSD (ischemic cardiomyopathy/non-ischaemic cardiomyopathy before AF diagnosis, primary valve disease, inherited cardiomyopathy). * Any pregnancy during AF or in the 12 months preceding LVSD onset. * Alcohol intake \>21 units/week. * Any history of cardiotoxic chemotherapy. AF/HF non-responders (Positive controls) * No alternative cause for LVSD (ischemic cardiomyopathy/non-ischaemic cardiomyopathy before AF diagnosis, primary valve disease, inherited cardiomyopathy). * Any pregnancy during AF or in the 12 months preceding LVSD onset. * Alcohol intake \>21 units/week. * Any history of cardiotoxic chemotherapy.
Where this trial is running
London
- St Bartholomew's Hospital, Barts Health NHS Trust — London, United Kingdom (Recruiting)
Study contacts
- Principal investigator: Shohreh Honarbakhsh, MBBS, PhD — Queen Mary University of London
- Study coordinator: Nikhil Ahluwalia, MBBS, PhD
- Email: nikhil.ahluwalia@nhs.net
- Phone: +44(0) 20 3465 5398
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.