Amyloidosis Cardiac
Conditions
Brief summary
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.
Detailed description
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.
Interventions
COMBINATION_PRODUCTSonotherapy
Use of high mechanical index ultrasound therapy with intravenous Definity contrast infusion
Sponsors
Brigham and Women's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Outcome measures will be evaluated before and after intervention with sonotherapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial Blood Flow | 1 day | N-13 ammonia or Rubidium-82 PET based measure of myocardial blood flow in ml/gm/min |
| Systolic Function | 1 day | Global Longitudinal Strain by echocardiography |
| Diastolic Function | 1 day | Echo measured mitral e' velocity |
Countries
United States
Contacts
CONTACTSharmila Dorbala, MD
PRINCIPAL_INVESTIGATORSharmila Dorbala, MD
Brigham and Women's Hospital
Outcome results
None listed