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.


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