AIC Genotyping Study
Genetic Susceptibility to AF-Induced Cardiomyopathy
Aperçu de l'étude
Statut
Les conditions
Description détaillée
Atrial Fibrillation (AF) is the most common heart rhythm disorder affecting 1 in 3-5 adults over 45. Although most patients tolerate AF, in some people it can weaken the main pump of the heart (left ventricle), causing heart failure. It is not known why some people develop heart failure during AF and others do not. We propose that individual vulnerability is due to specific genetic abnormalities that do not cause problems until they develop AF. These genetic abnormalities have been identified in patients who develop heart failure with the onset of other stressors, such as alcohol or pregnancy.
Our study will identify 92 patients with AF-triggered heart failure, defined by having heart failure during AF but resolved after the AF was treated using a procedure called catheter ablation. We will measure how common these genetic variations are seen in patients with AF-triggered heart failure and compare them with 184 patients who have AF but don't develop heart failure (negative comparators) and 23 patients who do develop heart failure but do not recover after AF treatment (positive comparators).We shall only test for a limited number of clearly disease-causing genetic variants to ensure cost- effectiveness and minimise the risk of identifying genes of unclear significance.
If we find a genetic association, doctors could: (1) identify patients more likely to develop weakness before the AF becomes persistent, (2) fast-track at-risk patients for catheter ablation treatment, (3) offer family screening where appropriate, and (4) avoid unnecessary testing in low-risk patients. This would directly improve care for people in East London and beyond by personalising AF treatment and preventing avoidable heart failure.
Type d'étude
Inscription (Estimé)
Contacts et emplacements
Coordonnées de l'étude
- Nom: Nikhil Ahluwalia, MBBS, PhD
- Numéro de téléphone: +44(0) 20 3465 5398
- E-mail: nikhil.ahluwalia@nhs.net
Lieux d'étude
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London, Royaume-Uni, EC1A 7BE
- Recrutement
- St Bartholomew's Hospital, Barts Health NHS Trust
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Contact:
- Nikhil Ahluwalia
- E-mail: nikhil.ahluwalia@nhs.net
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Méthode d'échantillonnage
Population étudiée
La description
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.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
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AF induced Cardiomyopathy (Cases)
Patients with LVSD during rate-controlled, persistent AF who improve their LVEF after sustained SR is achieved using catheter ablation or cardioversion.
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AF-preserved EF (Negative controls)
Patients without LVSD during rate-controlled, persistent AF
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AF/HF non-responders (Positive controls)
Patients with LVSD during rate-controlled, persistent AF who do not significantly improve their LVEF after sustained SR is achieved using catheter ablation or cardioversion.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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DCM gene prevalence relative to negative control
Délai: On day of baseline testing (1 day)
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Group difference between AIC vs AF-pEF in P/LP prevalence from DCM panel
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On day of baseline testing (1 day)
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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DCM gene prevalence relative to positive control
Délai: On day of baseline testing (1 day)
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Group difference between AIC vs AF/HF non-responders in P/LP prevalence.
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On day of baseline testing (1 day)
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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
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Genotype-recovery time association
Délai: 12 months post-ablation time-point (independent of study enrolment date)
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Time from durable SR to LVEF normalisation: by genotype (TTNtv; any P/LP): HR from Cox models. Change in LVEF (post-SR minus pre-SR) by genotype: β from linear regression. Rapid recovery proportion (normalisation ≤90 days) by genotype |
12 months post-ablation time-point (independent of study enrolment date)
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Shohreh Honarbakhsh, MBBS, PhD, Queen Mary University of London
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- 368232
Plan pour les données individuelles des participants (IPD)
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Informations sur les médicaments et les dispositifs, documents d'étude
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