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

Primary Purpose

Atrial Fibrillation, Heart Failure

Status

Recruiting

Phase

Not Applicable

Locations

United Kingdom

Study Type

Interventional

Intervention

Holter monitoring

stress echocardiography

Cardiac MRI

Patient questionnaires

About this trial

This is an interventional treatment trial for Atrial Fibrillation focused on measuring atrial fibrillation, heart failure

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

St Bartholomew's HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Arm Label

AF + HFrEF cohort

AF + symptoms cohort

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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

Full Information

NCT ID

NCT04987723

First Posted

July 14, 2021

Last Updated

January 4, 2023

Sponsor

Barts & The London NHS Trust

1. Study Identification

Unique Protocol Identification Number

NCT04987723

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 21, 2022 (Actual)

Primary Completion Date

April 2024 (Anticipated)

Study Completion Date

October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Barts & The London NHS Trust

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Atrial Fibrillation, Heart Failure

Keywords

atrial fibrillation, heart failure

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

104 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

AF + HFrEF cohort

Arm Type

Other

Arm Description

Arm Title

AF + symptoms cohort

Arm Type

Other

Arm Description

Intervention Type

Other

Intervention Name(s)

Holter monitoring

Other Intervention Name(s)

Heart rate variability recording

Intervention Description

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

Intervention Name(s)

stress echocardiography

Other Intervention Name(s)

assessment of cardiac reserve

Intervention Description

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

Intervention Name(s)

Cardiac MRI

Intervention Description

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

Intervention Name(s)

Patient questionnaires

Other Intervention Name(s)

AFeQT questionnaire and the Barts AF PROM questionnaire

Intervention Description

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).

Primary Outcome Measure Information:

Title

Correlation co-efficient of HRV measures with change in cardiac function

Description

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

Time Frame

6 months after catheter ablation

Secondary Outcome Measure Information:

Title

Correlation co-efficient of LA strain with change in cardiac function

Description

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

Time Frame

6 months after catheter ablation

Title

Correlation co-efficient of HRV measures with change in score on validated AF PROM questionnaire

Description

This will be calculated for each study arm independently. The scores from the AFeQT survey Barts AF PROM survey will be used

Time Frame

6 months

Other Pre-specified Outcome Measures:

Title

Relative frequency of pre-specified genetic variants in participants retrospectively deemed to have AF-induced HF as compared to a reference cohort.

Time Frame

1 day [At baseline assessment]

Title

Correlation co-efficient between R-R intervals derived from single-lead ECG time-series from the selected devices whilst recording simultaneously.

Description

Correlation co-efficient (r) between HRV measured using gold standard ECG monitoring and wearable-derived HRV.

Time Frame

1 day [At baseline assessment]

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Richard Schilling

Phone

02037658635

richard.schilling@nhs.net

First Name & Middle Initial & Last Name or Official Title & Degree

Nikhil Ahluwalia

Phone

02037658635

nikhil.ahluwalia@nhs.net

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Richard Schilling

Organizational Affiliation

Barts & The London NHS Trust

Official's Role

Principal Investigator

Facility Information:

Facility Name

St Bartholomew's Hospital

City

London

ZIP/Postal Code

EC1A7BE

Country

United Kingdom

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Richard Schilling

Phone

07851263544

richard.schilling@nhs.net

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

24382410

Citation

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.

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

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