AIC Genotyping Study
Genetic Susceptibility to AF-Induced Cardiomyopathy
Descripción general del estudio
Estado
Condiciones
Descripción detallada
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.
Tipo de estudio
Inscripción (Estimado)
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Nikhil Ahluwalia, MBBS, PhD
- Número de teléfono: +44(0) 20 3465 5398
- Correo electrónico: nikhil.ahluwalia@nhs.net
Ubicaciones de estudio
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London, Reino Unido, EC1A 7BE
- Reclutamiento
- St Bartholomew's Hospital, Barts Health NHS Trust
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Contacto:
- Nikhil Ahluwalia
- Correo electrónico: nikhil.ahluwalia@nhs.net
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Método de muestreo
Población de estudio
Descripción
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 de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
Cohortes e Intervenciones
Grupo / 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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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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DCM gene prevalence relative to negative control
Periodo de tiempo: 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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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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DCM gene prevalence relative to positive control
Periodo de tiempo: 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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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Genotype-recovery time association
Periodo de tiempo: 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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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Shohreh Honarbakhsh, MBBS, PhD, Queen Mary University of London
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
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Otros números de identificación del estudio
- 368232
Plan de datos de participantes individuales (IPD)
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Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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