Electrophysiological Remodelling Secondary to Metabolic, Inflammatory and Cardiomyopathic Processes
试验速览
- 阶段
- 不适用
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Conduction velocity
研究概览
简要总结
Obesity, rheumatoid arthritis (RA) and gene-specific dilated cardiomyopathy (DCM) are common medical conditions. Small-scale studies have shown that these are associated with proarrhythmic changes on 12-lead electrocardiogram (ECG) and a higher risk of sudden cardiac death (SCD). However, these studies lack the deep electrophysiological phenotyping required to explain their observations. Electrocardiographic imaging (ECGi) is a non-invasive alternative to 12-lead ECG, by which epicardial potentials, electrograms and activation sequences can be recorded to study adverse electrophysiological modelling in greater depth and on a more focussed, subject-specific scale. Therefore, this study proposes to better define the risk of arrhythmia and understand the underlying adverse electrophysiological remodelling conferring this risk in three groups (obesity, RA and DCM). Firstly, data from two large, national repositories will be analysed to identify associations between routine clinical biomarkers and proarrhythmic 12-lead ECG parameters, to confirm adverse electrophysiological remodelling and a higher risk of arrhythmia. Secondly,ECGi will be performed before and after planned clinical intervention in obese and RA patients, and at baseline in titin-truncating variant (TTNtv)-positive and -negative DCM patients, to characterise the specific and potentially reversible conduction and repolarisation abnormalities that may underlie increased arrhythmic risk.
详细描述
Sudden cardiac death (SCD) occurs in groups that are neither traditionally considered high-risk nor have been the subject of large-scale studies. These include obesity, inflammatory arthropathy and gene-specific cardiomyopathy. Existing data to explain higher risk of arrhythmia in these cohorts rely on 12-lead ECG and therefore lack in-depth electrophysiological phenotyping. The investigators have access to the two large national data repositories providing a wealth of data to study risks of arrhythmia on a scale larger than any previously published study. They also have a proven track record of utilising electrocardiographic imaging (ECGi) to conduct in-depth investigation of electrophysiological remodelling to better characterise arrhythmic risk.
ECGi is a validated, noninvasive method of acquiring body surface potential data using 252-electrodes and combining it with subjectspecific heart-torso geometry from crosssectional imaging. Using inverse solution mathematical algorithms, the ECGi system reconstructs epicardial unipolar electrograms and panoramic activation and potential maps over a single sinus beat, which is visualised on a digitised image of the subject's heart. Various studies have demonstrated the efficacy of ECGi to localise ventricular arrhythmias; more accurately calculate QT interval dispersion than 12-lead ECGs in obesity; and characterise ventricular tachycardia (VT) with intramural re-entry following myocardial infarction-induced scarring.
The study aims to confirm that obesity, RA and DCM are risk factors for arrhythmia and associated with electrophysiological remodelling manifest on 12-lead ECG, using large data repositories. The investigators will also perform electrocardiographic imaging (ECGi) to investigate and understand specific, and potentially reversible, conduction and repolarisation abnormalities conferring risk of arrhythmia in these cohorts using ECGi.
Hypotheses:
- Routine clinical biomarkers correlate with proarrhythmic 12-lead ECG parameters
- Adverse (proarrhythmic) electrophysiological remodelling can be quantified with ECGi
- Bariatric surgery reverses adverse electrophysiological remodelling in obesity
- Pharmacological therapy reverses adverse electrophysiological remodelling in RA
- TTNtv is associated with adverse electrophysiological remodelling in DCM
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •patients with obesity (BMI>40) who will undergo stapled bariatric surgery
- •RA, prior to commencement of disease-modifying drugs
- •TTNtv-positive or -negative DCM
- •no known existing medical condition or health concerns i.e. healthy volunteers;
- •aged 18 to 75 years, inclusive
排除标准
- •aged under 18 or over 75 years;
- •known HIV, hepatitis B & C or vCJD infection;
- •unable to provide verbal or signed written informed consent;
- •pregnancy or positive urinary pregnancy test;
- •breastfeeding
结局指标
主要结局
Conduction velocity
时间窗: 30 months approximately ie at the end of the study
Electrocardiographic parameter
Activation-recovery intervals
时间窗: 30 months approximately ie at the end of the study
Electrocardiographic parameter
次要结局
未报告次要终点