The Effect of Metoprolol on Myocardial Function, Perfusion, Hemodynamics and Heart Failure Symptoms in Patients With Hypertrophic Obstructive Cardiomyopathy.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- ∆Pulmonary capillary wedge pressure (rest-exercise)
研究概览
简要总结
Hypertrophic obstructive cardiomyopathy (HOCM) patients often develop disabling symptoms of heart failure. Current treatment strategies are predicated on the empirical use of long-standing drugs, such as beta-adrenergics, although with little evidence supporting their clinical benefit in this disease. Metoprolol is currently the most widely used beta-blocker in symptomatic HOCM patients, but a randomized, placebo-controlled trial, that looks at the effect in HOCM patients has never been conducted. No studies of HOCM combine invasive pressure measurement with exercise and echocardiography. All previous studies, both invasive and echocardiographic, have been conducted during rest, and not during exercise. Symptoms of HOCM patients are function-related, and exercise testing is essential to assess the condition and the effect of drugs.
详细描述
Background Hypertrophic cardiomyopathy (HCM) is characterized by an increase in left-ventricular wall thickness, typically localized at the interventricular septum. The hypertrophy can increase to an extend that causes a dynamic obstruction of the left ventricular outflow tract (LVOTO); these patients have hypertrophic obstructive cardiomyopathy (HOCM). Due to the obstruction, patients develop high interventricular pressure gradients, which may overtime become detrimental to the left ventricular function.
HOCM patients often develop disabling symptoms of heart failure. Current treatment strategies are predicated on the empirical use of long-standing drugs, such as beta-adrenergics, although with little evidence supporting their clinical benefit in this disease. Metoprolol is currently the most widely used beta-blocker in symptomatic HOCM patients, but a randomized, placebo-controlled trial, that looks at the effect in HOCM patients has never been conducted. No studies of HOCM combine invasive pressure measurement with exercise and echocardiography. All previous studies, both invasive and echocardiographic, have been conducted during rest, and not during exercise. Symptoms of HOCM patients are function-related, and exercise testing is essential to assess the condition and the effect of drugs.
Objective The investigators wants to quantify the effects of metoprolol on myocardial function and perfusion, hemodynamics and heart failure symptoms in patients with HOCM.
Hypotheses
Primary
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •Wall thickness ≥ 15 mm in one or more myocardial segments that is not explained by loading conditions.
- •LVOT gradient > 30 mmHg at rest and/or > 50 mmHg at Valsalva's maneuver or exercise
- •New York Heart Association Functional class (NYHA) ≥ II
排除标准
- •Age < 18 years
- •Known allergy to trial medicine
- •Contraindications to beta-blocker treatment
- •Contraindications to Magnetic resonans scan, including contraindication to the contrast agent gadolinium.
- •Female patients who are pregnant (positive plasma-HCG), breastfeeding or of child-bearing potential while not practicing effective chemical contraceptive hormones.
- •In case of patients having a pacemaker, they may not be pace-dependent.
- •Treatment with Amiodarone
- •Atrial fibrillation/flutter at the time of examination
- •Bradycardia < 49 beats/min
- •Systolic blood pressure < 100 mmHg
- •Trifascicular block
- •Previous transcoronary ablation of septum hypertrophy (TASH) or myectomy
- •Current abuse of alcohol and/or drugs
- •Significant co-morbidity or issues that makes the patient unsuitable for participation, judged by the investigator
- •Patients who cannot give valid consent (e.g. mental illness or dementia)
- •Patients who do not understand danish
研究组 & 干预措施
Metoprolol Succinate
Metoprololsuccinat
干预措施: Metoprolol Succinate (Drug)
Placebo oral capsule
Placebo
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
∆Pulmonary capillary wedge pressure (rest-exercise)
时间窗: Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms
Changes in pulmonary capillary wedge pressure in mmHg from rest to exercise, measured during right heart catheterization
次要结局
- LVOT gradient during maximum exercise(Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms)
- Coronary flow reserve(Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms)
- N-terminal prohormone of brain natriuretic peptide(Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms)
- Changes of symptoms and quality of life with Kansas City Cardiomyopathy Questionnaire(Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms)
- Pulmonary capillary wedge pressure at rest(Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms)
- VO2-max(Changes will be evaluated after an expected average of 2 weeks of treatment in both treatment arms)
研究者
Steen Hvitfeldt Poulsen
Senior consultant, DMSc, Aarhus University Hospital
Aarhus University Hospital Skejby