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

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04987723
• Other study ID #: 272775
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 21, 2022
• Est. completion date: October 2024

Study information

• Verified date: February 2024
• Source: Barts & The London NHS Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 106
• Est. completion date: October 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Atrial Fibrillation
• Heart Failure

Intervention

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.
• 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.
• 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).
• 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).

Locations

Country	Name	City	State
United Kingdom	St Bartholomew's Hospital	London

Sponsors (1)

Lead Sponsor	Collaborator
Barts & The London NHS Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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]
Other	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]
Primary	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	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
Secondary	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