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Dr Shaun Evans, Royal Adelaide Hospital, SA

Shaun’s Project : PREDICTive value of aggressive risk factor modification on the occurrence of major cardiovascular events in patients with embolic STROKE: PREDICT-STROKE

Synopsis:

PREDICT-STROKE is a randomised, multicentre trial to evaluate the potential benefits of aggressive risk factor modification versus standard of care to prevent major adverse cardiovascular events in patients with an embolic stroke or transient ischaemic attack.

Stroke is a major contributor to cardiovascular morbidity and mortality, resulting in lost quality of life, economic productivity, and health expense. Approximately one third of all strokes are attributable to atrial fibrillation, and a further third are cryptogenic (without known cause). Most cryptogenic strokes are subclassified as embolic stroke of undetermined source (ESUS). Approximately 3/10 patients with ESUS will be diagnosed with AF with prolonged monitoring.

Atrial cardiomyopathy is a relatively novel concept which encompasses pathological changes in the left atrium leading to the development of AF, or atrial thrombus and cardioembolism (potentially in the absence of AF). Multiple known factors influence atrial cardiomyopathy, and these include hypertension, obesity, diabetes, sleep apnoea and systemic inflammation.

We aim to test the hypothesis that aggressive management of these factors in a patient- specific fashion will prevent recurrent clinical and radiological embolic stroke.

The primary aim of the study is to investigate for patients with embolic stroke or transient ischaemic attack, whether the risk of major adverse cardiovascular events (including recurrent embolic stroke) can be modified by aggressive risk factor prevention.

For the diagnosis of atrial cardiomyopathy, invasive electroanatomical atrial mapping is known to demonstrate electrical atrial scar and regions of low voltage – the characteristic electrical changes of atrial cardiomyopathy. We aim to show that a multielectrode vest used to perform electrocardiographic imaging (ECGi) will correlate with invasive electroanatomical atrial mapping, predicting its extent and assist in stratifying risk of future atrial fibrillation.

We hypothesise that aggressive risk factor modification will reverse atrial cardiomyopathy, and that serial ECGi mapping will be able to demonstrate concordant longitudinal changes.

Systemic inflammation is closely related to the risk of developing AF, as shown by its relationship to multiple biomarkers of inflammation. We aim to investigate the relationship between these biomarkers and the extent of atrial cardiomyopathy as diagnosed by ECGi.

The primary potential benefit of this study is the identification of directed therapy for secondary prevention of embolic stroke of undetermined source. More generally, we expect a reduction in cardiovascular disease, which will provide individual patient benefit. With risk factor modification, we anticipate a group-level effect in weight reduction, blood pressure management and lifestyle improvement, which each have public health benefits for reduced incidence of atherosclerotic cardiovascular disease and improved mental health.

A clinically significant reduction in the primary endpoint of the study would translate to reduced hospitalisations, preserved quality of life, preserved cognitive function, freedom from physical disability and overall reduced healthcare expenditure.