Clinical trial NCT04987723: 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
Overall status: COMPLETED
Phase: NA
Conditions: Atrial Fibrillation
Heart Failure
Keywords: atrial fibrillation
heart failure
Lead sponsor: Barts & The London NHS Trust
Sponsor class: OTHER
First posted: 2021-08-03
Enrollment: 106
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Correlation co-efficient of HRV measures with change in cardiac function
timeFrame: 6 months after catheter ablation
Secondary outcomes:
measure: Correlation co-efficient of LA strain with change in cardiac function
timeFrame: 6 months after catheter ablation
measure: Correlation co-efficient of HRV measures with change in score on validated AF PROM questionnaire
timeFrame: 6 months
Other outcomes:
measure: Relative frequency of pre-specified genetic variants in participants retrospectively deemed to have AF-induced HF as compared to a reference cohort.
timeFrame: 1 day [At baseline assessment]
measure: Correlation co-efficient between R-R intervals derived from single-lead ECG time-series from the selected devices whilst recording simultaneously.
timeFrame: 1 day [At baseline assessment]
Locations:
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
Study officials:
affiliation: Barts & The London NHS Trust
name: Richard Schilling
role: PRINCIPAL_INVESTIGATOR
References:
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.