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

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Atrial Fibrillation
• Intervention / Treatment: Other: Holter monitoring; Other: stress echocardiography; Other: Cardiac MRI; Other: Patient questionnaires

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, EC1A7BE
    • St Bartholomew's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 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.	Other: 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.; Other Names: Heart rate variability recording; 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.; Other Names: assessment of cardiac reserve; 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).; 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).; Other Names: AFeQT questionnaire and the Barts AF PROM questionnaire
Other: 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.	Other: 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.; Other Names: Heart rate variability recording; 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).; Other Names: AFeQT questionnaire and the Barts AF PROM questionnaire

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation co-efficient of HRV measures with change in cardiac function	This will be calculated in the AF + HFreF arm Cardiac function will be measured as three endpoints: LVEF on echocardiography; Serum NT-proBNP; VO2 peak on CPET	6 months after catheter ablation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation co-efficient of LA strain with change in cardiac function	This will be calculated in the AF + HFreF arm Cardiac function will be measured as three endpoints: LVEF on echocardiography; Serum NT-proBNP; VO2 peak on CPET	6 months after catheter ablation
Correlation co-efficient of HRV measures with change in score on validated AF PROM questionnaire	This will be calculated for each study arm independently. The scores from the; AFeQT survey; Barts AF PROM survey will be used	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative frequency of pre-specified genetic variants in participants retrospectively deemed to have AF-induced HF as compared to a reference cohort.		1 day [At baseline assessment]
Correlation co-efficient between R-R intervals derived from single-lead ECG time-series from the selected devices whilst recording simultaneously.	Correlation co-efficient (r) between HRV measured using gold standard ECG monitoring and wearable-derived HRV.	1 day [At baseline assessment]

Collaborators and Investigators

• Sponsor: Barts & The London NHS Trust
• Investigators: Principal Investigator: Richard Schilling, Barts & The London NHS Trust

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2022
• Primary Completion (Actual): October 31, 2024
• Study Completion (Actual): October 31, 2024

Study Registration Dates

• First Submitted: July 14, 2021
• First Submitted That Met QC Criteria: July 28, 2021
• First Posted (Actual): August 3, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 7, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: atrial fibrillation; heart failure
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Heart Failure; Atrial Fibrillation
• Other Study ID Numbers: 272775

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No