The Role of Sodium Glucose Cotransporter 2 Inhibitors in the Management of Patients With Aortic Stenosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Change in indexed extracellular volume (iECV)
研究概览
简要总结
Background:
The aortic valve is like a door in the heart that lets blood flow out to the body. Over time, this valve can get worn out and become too narrow, leading to a condition called aortic stenosis. When this happens, the heart has to work extra hard to push blood through the narrow valve to supply the body with what it needs. This extra effort can cause the heart muscle to become abnormally thick or to have fibrosis. For people with aortic stenosis, this can lead to more problems like feeling out of breath, chest pain, and even needing to go to the hospital. It also increases the risk of dying from heart issues. There is a type of medication called Sodium Glucose Cotransporter 2 (SGLT2) inhibitors, which has been studied in people with weak heart muscle. These medicines were found to help the heart work better and improve the pumping of blood around the body. This can be promising for patients with aortic stenosis because it might make the heart muscle stronger and protect it from damage.
Aim of research study:
The aim of this study is to investigate whether the use of the drug empagliflozin, an SGLT2 inhibitor, prevents the formation of fibrosis or the abnormal thickening of the heart muscle in patients with aortic stenosis. Using advanced imaging techniques (such as echocardiography and cardiovascular magnetic resonance), we intend to study their effect on the heart muscle of patients with aortic stenosis.
Study design:
Patients with moderate aortic stenosis will be invited for participation. Eligible consenting patients will have a baseline assessment with cardiac MRI scan, echocardiography, cardiopulmonary exercise test and validated quality of life questionnaires. They will then be randomised to receive either the SGLT2i for 6 months, or standard of care. All patients will undergo the same tests at 6 months. This way, we aim to investigate the potential changes in the heart muscle and whether the SGLT2 inhibitor prevents fibrosis or hypertrophy.
详细描述
Background:
Aortic stenosis represents one of the commonest valvular heart diseases in the Western World. Studies have shown that as the valvular narrowing progresses, pathological left ventricular (LV) hypertrophy and fibrosis develop. This maladaptive left ventricular remodelling is associated with adverse events and worse long-term prognosis. Currently, there is no available medication to slow down or prevent these pathological processes occurring in aortic stenosis. Evidence from recent large randomised controlled trials have demonstrated that SGLT2 inhibitors have a significant positive impact on quality of life and cardiovascular outcomes of patients with heart failure. This is a result of complex mechanisms such as attenuation of cardiac myofibroblast activity and collagen remodelling. These could be proved to be very beneficial for patients with aortic stenosis since the left ventricular pathological changes occurring in aortic stenosis share similar pathways and mechanisms with heart failure.
Study aims and objectives:
The aims of this study are to assess if:
- SGLT2 inhibitors can prevent or decelerate adverse myocardial remodelling and fibrosis.
- SGLT2 inhibitors can improve the exercise tolerance and functional capacity of patients with aortic stenosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Moderate aortic stenosis (aortic valve peak velocity ≥ 3m/s or mean gradient 20-40mmHg, or Aortic valve area 1.0-1.5cm2)
- •Age over 18 years
排除标准
- •Severe aortic stenosis (aortic valve peak velocity ≥ 4m/s or mean > 40mmHg or Aortic valve area < 1.0cm2) or planned cardiac surgery or likely need for surgery within 6 months.
- •Previous valve replacement
- •Severe hypertension (systolic >180mmHg or diastolic >100mmHg)
- •Acute pulmonary oedema or cardiogenic shock
- •Coexisting other valvular lesion of more than moderate severit.
- •Coexisting hypertrophic cardiomyopathy or amyloidosis with cardiac involvement
- •Any contraindications to MRI scanning including eGFR <30ml/min/1.73m2
- •Pregnancy or breast-feeding
- •Concomitant SGLT2 inhibitor therapy
- •Inability to receive SGLT2 inhibitor therapy
- •History of diabetes type 1 or 2
- •Severe peripheral vascular disease or non-healed leg ulcers
- •Severe liver disease
- •Rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption
研究组 & 干预措施
Control Group
Patients randomised in this group will continue to have their guideline directed conservative management with no changes in their regular medications.
Intervention Group
Patients randomised in this group will be taking the SLGT2 inhibitor (empagliflozin) on top of their regular medications for 6 months.
干预措施: Empagliflozin 10 MG (Drug)
结局指标
主要结局
Change in indexed extracellular volume (iECV)
时间窗: 6 months
The indexed extracellular volume (iECV) (expressed in ml/m2) will be assessed from the Cardiac Magnetic Resonance Scan at baseline and at 6 months follow-up
次要结局
- Change in left ventricular diastolic function as assessed by the E/A ratio(6 months)
- Change in indexed left ventricular mass(6 months)
- Change in cardiac markers (N-terminal pro b-type natriuretic peptide and high sensitivity troponin)(6 months)
- Change in Quality of Life (QoL) as assessed with the Kansas City Cardiomyopathy Questionnaire(6 months)
- Change in left ventricular ejection fraction(6 months)
- Change in peak oxygen consumption (VO2) as assessed by Cardio-Pulmonary Exercise Test(6 months)
- Change in percentage of myocardial uptake of late gadolinium enahncement (LGE)(6 months)