A Mechanistic Exploratory Study of AF-induced Cardiac Dysfunction and Symptoms

NCT ID: NCT04987723

Last Updated: 2025-02-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 106 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-21
• Study Completion Date: 2024-10-31

Brief Summary

Although the heart rhythm disorder Atrial Fibrillation (AF) affects 2% of the population, the impact it has on an effected individual can be highly variable. Some people are asymptomatic whilst others can experience debilitating symptoms or heart failure (HF)- weakness of the heart muscle. The reason why this variability exists in unknown and how AF actually drives HF is unclear. HF can also be caused by many other reasons and it can be difficult to identify those patients with HF caused by AF versus patients with AF but their HF is due to a different reason. This is important as it would help us to identify those patients most likely to improve their heart function after the treatment of AF and thus gain more from invasive treatments like AF catheter ablation; which is effective at restoring normal heart rhythm but has some risks attached.

The investigators suspect the characteristics of the AF, such as how irregularly it makes the heartbeat, can be used to predict who will respond better. Studies of heart cells in the lab as well as animal models have suggested this characteristic may be the cause of AF-induced heart muscle weakness and reduce cardiac output, making it a potential predictor that can be measured. Other potential predictors will be measured during pre-procedural scans and tests too. The investigators will also explore whether there are predictors of which patients gain the most symptomatic benefit and gain insight into why some people develop symptoms of AF, whereas others do not.

By studying the structural and functional sequelae of catheter ablation in patients with HF the investigators hope to better understand the relationship between the two diseases.

Conditions

Atrial Fibrillation; Heart Failure

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AF + HFrEF cohort

Left Ventricular Ejection Fraction (LVEF) < 50% by echocardiogram during routine screening or within 12 months prior to enrolment day. The echo must have been performed >3 weeks after optimisation of HF and rate control therapies, otherwise repeat imaging will be performed after this has been achieved

With

NYHA functional status II-III at the enrolment visit.

Group Type: OTHER

Holter monitoring

Intervention Type: OTHER

Assessment of HRV shall be performed in all enrolled patients. Ventricular HRV will be derived from a continuous 24-hour period of a 48-hour ambulatory Holter recording during AF. Participants will be requested to avoid alcohol and caffeine from 24-hours prior to fitting and any activity more strenuous than walking for the recording duration. After initial fitting, a 20-minute high-resolution ECG recording will be performed lying supine at rest.

stress echocardiography

Intervention Type: OTHER

Echocardiography will be performed using a GE Vivid 9 echocardiography machine (Vingmed-General Electric, Horten, Norway) equipped with a phased-array 3.5 MHz transducer. All measurements will be made according to the guidelines set by the British Society of Echocardiography.

Cardiac MRI

Intervention Type: OTHER

Contraindications to MRI will be excluded using the appropriate departmental screening forms. A trained scanner operator or radiographer will co-ordinate and supervise the scan. Cardiac MRI will be performed at 1.5T (Aera, Siemens Healthineers, Erlangen, Germany) with a protocol consisting of cine imaging, stress and rest perfusion, and late gadolinium enhancement (LGE).

Patient questionnaires

Intervention Type: OTHER

Two validated Health Related Quality of Life (HRQoL) surveys designed for patients with AF will be used; the AF Effect on Quality of Life (AFEQT) and Barts AF Patient reported objective measure (PROM).

AF + symptoms cohort

Left Ventricular Ejection Fraction (LVEF) > 50% by echocardiogram during routine screening or within 12 months prior to enrolment day

With

modified European Heart Rhythm Association symptom classification 2b-4.

Group Type: OTHER

Holter monitoring

Intervention Type: OTHER

Assessment of HRV shall be performed in all enrolled patients. Ventricular HRV will be derived from a continuous 24-hour period of a 48-hour ambulatory Holter recording during AF. Participants will be requested to avoid alcohol and caffeine from 24-hours prior to fitting and any activity more strenuous than walking for the recording duration. After initial fitting, a 20-minute high-resolution ECG recording will be performed lying supine at rest.

Patient questionnaires

Intervention Type: OTHER

Two validated Health Related Quality of Life (HRQoL) surveys designed for patients with AF will be used; the AF Effect on Quality of Life (AFEQT) and Barts AF Patient reported objective measure (PROM).

Interventions

Holter monitoring

Assessment of HRV shall be performed in all enrolled patients. Ventricular HRV will be derived from a continuous 24-hour period of a 48-hour ambulatory Holter recording during AF. Participants will be requested to avoid alcohol and caffeine from 24-hours prior to fitting and any activity more strenuous than walking for the recording duration. After initial fitting, a 20-minute high-resolution ECG recording will be performed lying supine at rest.

Intervention Type: OTHER

stress echocardiography

Echocardiography will be performed using a GE Vivid 9 echocardiography machine (Vingmed-General Electric, Horten, Norway) equipped with a phased-array 3.5 MHz transducer. All measurements will be made according to the guidelines set by the British Society of Echocardiography.

Intervention Type: OTHER

Cardiac MRI

Contraindications to MRI will be excluded using the appropriate departmental screening forms. A trained scanner operator or radiographer will co-ordinate and supervise the scan. Cardiac MRI will be performed at 1.5T (Aera, Siemens Healthineers, Erlangen, Germany) with a protocol consisting of cine imaging, stress and rest perfusion, and late gadolinium enhancement (LGE).

Intervention Type: OTHER

Patient questionnaires

Two validated Health Related Quality of Life (HRQoL) surveys designed for patients with AF will be used; the AF Effect on Quality of Life (AFEQT) and Barts AF Patient reported objective measure (PROM).

Intervention Type: OTHER

Other Intervention Names

Heart rate variability recording; assessment of cardiac reserve; AFeQT questionnaire and the Barts AF PROM questionnaire

Eligibility Criteria

Inclusion Criteria

• Referred for first AFCA procedure by their responsible physician.
• Persistent AF captured on ECG but not in continuous AF for more than 3 years. (Persistent AF will be defined as any continuous episode lasting longer than 7 days or requiring intervention to restore sinus rhythm after this time.)
• Participants must have either:

• Left Ventricular Ejection Fraction (LVEF) < 50% by echocardiogram during routine screening or within 12 months prior to enrolment day. The echo must have been performed >3 weeks after optimisation of HF and rate control therapies, otherwise repeat imaging will be performed after this has been achieved

With:

o NYHA functional status II-III at the enrolment visit.

Or:

o Left Ventricular Ejection Fraction (LVEF) >50% by echocardiogram during routine screening or within 12 months prior to enrolment day.

With:

o modified European Heart Rhythm Association 2a-4.

Exclusion Criteria

• Previous left atrial ablation procedure or surgery.
• Contraindication to chronic anticoagulation therapy or heparin
• Unable or unwilling to consent to investigation and follow-up requirements or inability to comply with planned study procedures.
• LA anteroposterior diameter ≥ 5.5 cm or indexed LA volume ≥ 50mL/m2 on echo.
• Recent (last 6 months) event that may impact LV function- myocardial infarction, coronary revascularization, pacemaker or cardiac resynchronization therapy.
• AF suspected to be due to a reversible cause (e.g. hyperthyroidism, recent surgery)
• Acute coronary syndrome within 4 weeks as defined by ECG ST segment depression or prominent T-wave inversion and/or positive biomarkers of necrosis (e.g. troponin) in the absence of ST-segment elevation and in an appropriate clinical setting (chest discomfort or angina equivalent).
• Cardiac surgery, angioplasty, or cerebrovascular accident within 4 weeks prior to enrolment.
• Life expectancy less than 1 year.
• Chronic kidney disease stage 4 or 5.
• Any of the below cardiac diagnoses:

• Hypertrophic obstructive cardiomyopathy
• Severe valvular disease
• Restrictive or constrictive cardiomyopathy, including known amyloidosis, sarcoidosis,
• haemochromatosis
• Complex congenital heart disease
• Constrictive pericarditis
• Severe pulmonary hypertension (RVSP > 60 mmHg),
• Non-cardiac pulmonary oedema
• Active myocarditis

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Barts & The London NHS Trust

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard Schilling

Role: PRINCIPAL_INVESTIGATOR

Barts & The London NHS Trust

Locations

St Bartholomew's Hospital

London, , United Kingdom

Countries

United Kingdom

References

Hunter RJ, Berriman TJ, Diab I, Kamdar R, Richmond L, Baker V, Goromonzi F, Sawhney V, Duncan E, Page SP, Ullah W, Unsworth B, Mayet J, Dhinoja M, Earley MJ, Sporton S, Schilling RJ. A randomized controlled trial of catheter ablation versus medical treatment of atrial fibrillation in heart failure (the CAMTAF trial). Circ Arrhythm Electrophysiol. 2014 Feb;7(1):31-8. doi: 10.1161/CIRCEP.113.000806. Epub 2014 Jan 1.

Reference Type: BACKGROUND

PMID: 24382410 (View on PubMed)

Ahluwalia N, Honarbakhsh S, Abbass H, Joshi A, Chow AWC, Dhinoja M, Petersen SE, Hunter RJ, Lloyd G, Schilling RJ. Characterisation of patients who develop atrial fibrillation-induced cardiomyopathy. Open Heart. 2024 Nov 27;11(2):e002955. doi: 10.1136/openhrt-2024-002955.

Reference Type: DERIVED

PMID: 39608861 (View on PubMed)

Other Identifiers

272775

Identifier Type: -

Identifier Source: org_study_id