Ultrasound Therapy In Cardiac Amyloidosis

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) andin hematological remission (normal serum free light chain levels)

• (immunofixation of serum and urine, IgG free light chain (FLC) assay, a biopsyof fat pad/ bone marrow, or organ biopsy, followed by typing of the light chainusing immunohistochemistry or immunogold assay with confirmation by Massspectroscopy as needed) AND

• proof of cardiac involvement by AL amyloidosis

• abnormal cardiac biomarkers (Abnormal high sensitivity TnT 5th generationlevels (>9 ng/L: female, >14 ng/L: male) or abnormal age appropriate N terminalpro-brain natriuretic peptide, NT-proBNP (abnormal values: <50 years: >450pg/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 usingimmunohistochemistry or immunogold assay with confirmation by Mass spectroscopyas needed

• extracardiac biopsy with typical cardiac imaging findings, or

• grade 2 or grade 3 myocardial uptake of technetium-99m pyrophosphate (PYP) ifAL 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 ordilated 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 anysingle 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 transientright-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 greaterthan 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 poorcandidate for ultrasound therapy