Manganese-Enhanced Magnetic Resonance Imaging (MEMRI) in Ischaemic, Inflammatory and Takotsubo Cardiomyopathy (MEMORY)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- Manganese uptake (Ki)
研究概览
简要总结
Manganese is a calcium analogue which actively enters viable cells with intact calcium-handling mechanisms and its uptake is evident by an increase in MRI-detectable T1 relaxivity of tissues. Mangafodipir is a novel manganese-based magnetic resonance imaging (MRI) contrast medium with unique biophysical properties that are ideal for application to cardiac imaging. Recent studies in man have demonstrated the utility of manganese-enhanced MRI (MEMRI) in assessing infarct size more accurately than with standard cardiac MRI protocols using gadolinium enhancement and have shown reduced myocardial manganese uptake in patients with cardiomyopathies suggesting abnormal calcium handling.
Understanding the potential for myocardial recovery is key in guiding revascularisation therapies in ischaemic cardiomyopathy, in addition to novel therapies used in heart failure. Being able to monitor calcium handling and therefore myocardial function in different types of cardiomyopathies has the potential to guide management in these patients. The investigators here propose an investigational observational study of MEMRI to assess myocardial calcium handling in reversible causes of cardiomyopathy, namely ischaemic cardiomyopathy, myocarditis and takotsubo cardiomyopathy.
详细描述
BACKGROUND Heart failure (HF) is a global pandemic affecting at least million people worldwide. Despite the significant advances in therapies and prevention, mortality and morbidity are still high and quality of life poor.
Cardiomyopathy refers to diseases affecting the myocardium which can lead to heart failure.
Ischaemic heart disease (IHD) is the leading cause of cardiovascular morbidity and mortality in the United Kingdom (UK) and an important cause of reversible cardiomyopathy.
Takotsubo cardiomyopathy (TTS) is a form of stress cardiomyopathy that is characterised by acute, transient left ventricular (LV) dysfunction. This typically affects the apex extending beyond a single epicardial vessel with subsequent angiography revealing non obstructive coronaries. It accounts for up to 2% of acute coronary syndrome (ACS) admissions and despite being first described 20 years ago its pathophysiology is poorly understood. Typically takotsubo resolves over time and is considered to have a benign prognosis however acutely it can cause serious complications such as severe heart failure, cardiac arrhythmias and cardiac arrest.
Myocarditis is an inflammatory cardiomyopathy with varying aetiology which comprises a wide clinical spectrum from sub-clinical disease to severe heart failure. Currently myocardial biopsy is considered the gold standard in diagnosis, although it is prone to sample error and clinically indicated in only a few scenarios. Although in some cases cardiac MRI can reveal a 'typical' pattern of myocarditis based on T2 oedema imaging, the sensitivity and specificity is unclear and not yet established giving a limited diagnostic yield. Myocarditis may resolve spontaneously, recur or become chronic. In a third of biopsy-proven cases, it can lead to heart failure, cardiac transplantation or death. As a result, it has significant contribution to the global burden of cardiovascular disease.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All subjects to be entered must:
- •≥ 18 years of age
- •if female, be non-pregnant as evidenced by a urine pregnancy test or post-menopausal or surgically sterile
- •provide written informed consent after having received oral and written information about the study
- •Additionally, cohort-specific inclusion criteria as follows:
- •Healthy adult with no known pre-existing medical conditions
- •Positive stress- akinesia/hypokinesis on pharmacological stress
- •Negative stress- no inducible regional wall motion abnormalities on pharmacological stress
- •New left/right ventricular dysfunction; including regional wall motion abnormalities (RWMA's)
- •New abnormal ECG findings (conduction, atrio-ventricular block, ST/T wave changes)
- •Raised biomarkers (troponin, TnI)
- •Tissue characteristics on MRI (myocardial oedema and typical late gadolinium enhancement pattern)
- •Normal/ Non-obstructive coronaries on angiography
- •Typical RWMA's based on echocardiography, MRI or left ventriculography
排除标准
- •The following apply to all participants:
- •have a positive pregnancy test
- •women who are breast feeding
- •received an investigational drug or device within 30 days prior to administration of Mangafodipir
- •have a history of ongoing drug abuse or alcoholism
- •have a history of torsades or prolonged QT/QT corrected interval
- •high degree atrioventricular block (second or third degree)
- •atrial fibrillation or flutter
- •have New York Heart Failure Association (NYHA) Grade IV heart failure
- •have abnormal liver function tests (> x3 ULN) or a history of liver disease
- •have a baseline estimated glomerular filtration rate (eGFR) of <30 mL/min/1.73m2)
- •have uncontrolled hypertension (systolic blood pressure >200 mmHg)
- •have any contraindications to MRI, including implanted devices/pacemakers
- •be maintained on either a calcium channel blocker or digoxin
- •known diagnosis of pheochromocytoma
- •Additionally, cohort-specific exclusion criteria as follows:
- •Severe aortic stenosis (mean gradient >40 mmHg, mean aortic valve area ≤1 cm2 or peak velocity ≥4 m/sec)
- •Severe asthma/ chronic obstructive airways disease
- •Presence of coronary artery disease
- •Diagnosis of other cardiomyopathies (takotsubo, infiltrative, hypertrophic cardiomyopathy, dilated cardiomyopathy)
- •Myocardial fibrosis on magnetic resonance imaging
- •Evidence of myocarditis, hypertrophic cardiomyopathy, head trauma, and intra-cranial haemorrhage.
结局指标
主要结局
Manganese uptake (Ki)
时间窗: 2 years
Calculate myocardial manganese uptake using T1 maps
Myocardial T1 relaxation (ms)
时间窗: 2 years
Measure Manganese T1 values in different disease processes
次要结局
- LV function in Ejection Fraction (EF)(2 years)
- LV Relaxation(2 years)
- LV Mass (grams)(2 years)