Ultrasound Therapy In Cardiac Amyloidosis
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Systolic Function
研究概览
简要总结
This is a prospective pilot clinical study of subjects with cardiac amyloidosis and control subjects without amyloidosis where we plan to evaluate changes in myocardial blood flow, systolic and diastolic function before and after sonotherapy.
详细描述
70 subjects will be enrolled in this study in 3 study groups: A) 30 subjects with light chain cardiac amyloidosis B) 30 subjects with transthyretin cardiac amyloidosis and C) 10 subjects without amyloidosis. All subjects will undergo rest 2D echocardiography, rest N-13 ammonia or rubidium-82 perfusion PET, Definity infusion with high mechanical index (MI) imaging defined as sonotherapy in this study protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age > 18 years for AL-CA, > 65 years for ATTR-CA, > 65 years for controls
- •Willing and able to provide consent
- •Diagnosis of systemic light chain amyloidosis by standard criteria (see below) and in hematological remission (normal serum free light chain levels)
- •(immunofixation of serum and urine, IgG free light chain (FLC) assay, a biopsy of fat pad/ bone marrow, or organ biopsy, followed by typing of the light chain using immunohistochemistry or immunogold assay with confirmation by Mass spectroscopy as needed) AND
- •proof of cardiac involvement by AL amyloidosis
- •abnormal cardiac biomarkers (Abnormal high sensitivity TnT 5th generation levels (>9 ng/L: female, >14 ng/L: male) or abnormal age appropriate N terminal pro-brain natriuretic peptide, NT-proBNP (abnormal values: <50 years: >450 pg/ml; 50-75 years:>900 pg/ml; >75 years: >1800 pg/ml) or
- •abnormal echocardiogram (wall thickness > 12 mm) or
- •abnormal cardiac MRI (wall thickness > 12 mm or extracellular volume > 0.35) OR
- •Diagnosis of transthyretin cardiac amyloidosis by standard criteria
- •endomyocardial biopsy followed by typing of the transthyretin amyloidosis using immunohistochemistry or immunogold assay with confirmation by Mass spectroscopy as needed
- •extracardiac biopsy with typical cardiac imaging findings, or
- •grade 2 or grade 3 myocardial uptake of technetium-99m pyrophosphate (PYP) if AL amyloidosis is excluded
排除标准
- •Hemodynamic instability
- •Severe claustrophobia despite use of sedatives
- •Decompensated heart failure (unable to lie flat for 1 hour)
- •Concomitant non-ischemic non-amyloid heart disease (valvular heart disease or dilated cardiomyopathy)
- •Severe valve stenosis or regurgitation in the aortic, mitral or tricuspid valves, including prior valve replacement
- •Severe pulmonary artery hypertension
- •Severe lung disease
- •Known obstructive epicardial coronary artery disease with stenosis > 50% in any single territory
- •Prior cardiac surgery
- •Regional wall motion abnormality on echocardiogram
- •Left ventricular ejection fraction < 40%
- •Pregnant state
- •Documented allergy to N-13 ammonia or Definity
- •Contraindications to DEFINITY® (Perflutren Lipid Microsphere) Injectable Suspension:
- •o Patients with known or suspected Right-to-left, bi-directional, or transient right-to-left cardiac shunts, Hypersensitivity to perflutren
- •Contraindications or challenges to sonotherapy
- •Severe electrolyte abnormalities
- •QTc prolongation (values are greater than 450 milliseconds in males and greater than 470 milliseconds in females)
- •BMI > 35 kg/m2
- •Documented intracardiac thrombus
- •Atrial fibrillation not on anticoagulation
- •Prior history of stroke
- •Any other reason determined by the investigator that makes a subject a poor candidate for ultrasound therapy
研究组 & 干预措施
Sonotherapy
All participants will undergo sonotherapy
干预措施: Sonotherapy (Combination Product)
结局指标
主要结局
Systolic Function
时间窗: 1 day
Global Longitudinal Strain by echocardiography
Myocardial Blood Flow
时间窗: 1 day
N-13 ammonia or Rubidium-82 PET based measure of myocardial blood flow in ml/gm/min
Diastolic Function
时间窗: 1 day
Echo measured mitral e' velocity
次要结局
未报告次要终点
研究者
Sharmila Dorbala
Director, Nuclear Cardiology
Brigham and Women's Hospital