Myocardial Efficiency of the Left Ventricle in Asymptomatic Patients With Aortic Valve Stenosis - a Prognostic Marker and a Target for Intervention?
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- LV myocardial efficiency
研究概览
简要总结
Background - Aortic valve stenosis (AS) is the most common heart valve disease among adults in the Western world with a prevalence of 3 % in people older than 75 years of age. AS usually deteriorates over time leading to heart failure, with high mortality if aortic valve replacement (AVR) is not performed. Thus optimal timing of AVR is crucial, but can be challenging. Increasing life expectancy in our society will augment the therapeutic and socio economic impact of AS disease on our health care system. Therefore, new techniques for monitoring asymptomatic AS patients are needed. A potential approach is monitoring of LV myocardial efficiency (mechanical work/oxygen consumption). These measures have been suggested to be involved in the progression of non-valvular heart failure and closely related to prognosis, but never applied in a larger population of patients with AS. At present there are no recognized pharmacological treatments of AS. It is known that beta-blocker treatment in non-valvular systolic heart failure reduce heart rate, improves LV myocardial efficiency and reduces mortality. However, in patients with AS, the effects of beta-blockers are unknown.
Hypotheses - Treatment with the beta-blocker metoprolol succinate in patients with asymptomatic moderate to severe AS has beneficial effects on LV myocardial oxidative metabolism, myocardial efficiency and contractile function.
Objectives - To investigate if beta-blocker treatment in patients with moderate to severe, asymptomatic AS has beneficial effects on LV myocardial efficiency, contractile function and physical performance.
Design - A randomized double blind placebo controlled intervention trial. 40 patients with asymptomatic AS will be randomized to either per oral metoprolol succinate (N = 20) or placebo (N= 20) for 22 weeks.
Primary objective - Changes in myocardial efficiency
Secondary objectives - Myocardial oxygen consumption, Myocardial perfusion at rest, LV myocardial function, LVmass, Aortic valve area and transaortic valve velocities, 6 minute walking distance, N-terminal prohormone of brain natriuretic peptide, Quality of life (estimated by Minnesota living with heart failure questionnaire), LV wall stress
Methods - Patients will undergo echocardiography (resting and exercise), [11C]acetate PET and cardiac magnetic resonance imaging.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aortic valve area ≤1,2 cm2 and/or transaortic maximal velocity (VmaxAO) of 3,0-5,0 m/s
- •Sinus rhythm >60/min after 5 minutes of rest
- •LVEF >≥50%
- •Male or female
- •Age 20-100 years old
- •Safe birth control management for women of childbearing potential.
- •Negative urine-HCG for women of childbearing potential
- •Ability to understand the written patient information and to give informed consent
排除标准
- •Systolic BP <100 mmHg after 5 minutes of rest
- •Left ventricular posterior wall thickness >17 mm
- •Signs or history of major myocardial infarction and/or severe ischemic heart disease
- •Severe asthma or chronic obstructive pulmonary disease
- •New York Heart Association (NYHA) classification > I due to AS
- •NYHA > II due to non-cardiac causes
- •2ᵒ or 3ᵒ atrioventricular block
- •Ongoing beta-blocker therapy
- •Ongoing verapamil or diltiazem therapy
- •Ongoing monoamine oxidase inhibitors therapy (except MAO-B-inhibitors)
- •Sick sinus syndrome
- •Atrial fibrillation or fluttering
- •Lack of stable sinus rhythm
- •Pheochromocytoma
- •Severe peripheral vascular disease
- •Intolerance of Metoprolol succinate or its excipients
- •Other disease or treatment making subject unsuitable for study participation
- •Intolerance of tracer used for [11C]acetate PET recordings
- •Participation in other intervention study
研究组 & 干预措施
Active
Metoprololsuccinate
干预措施: Metoprololsuccinate (Drug)
Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
LV myocardial efficiency
时间窗: Changes will be evaluated after an expected average of 22 weeks of treatment
次要结局
- LV oxygen consumption(Changes will be evaluated after an expected average of 22 weeks of treatment)
- LV perfusion(Changes will be evaluated after an expected average of 22 weeks of treatment)
- LV myocardial function(Changes will be evaluated after an expected average of 22 weeks of treatment)
- LVmass(Changes will be evaluated after an expected average of 22 weeks of treatment)
- Aortic valve area(Changes will be evaluated after an expected average of 22 weeks of treatment)
- Transaortic valve velocities(Changes will be evaluated after an expected average of 22 weeks of treatment)
- 6 minute walking distance(Changes will be evaluated after an expected average of 22 weeks of treatment)
- N-terminal prohormone of brain natriuretic peptide(Changes will be evaluated after an expected average of 22 weeks of treatment)
- Quality of life - estimated by Minnesota living with heart failure questionnaire(Changes will be evaluated after an expected average of 22 weeks of treatment)
- LV wall stress(Changes will be evaluated after an expected average of 22 weeks of treatment)
研究者
Henrik Wiggers
Senior consultant, Assoc. professor, DMSc
Aarhus University Hospital