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) and inhematological remission (normal serum free light chain levels)
• (immunofixation of serum and urine, IgG free light chain (FLC) assay, a biopsy offat 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 generation levels (>9 ng/L: female, >14 ng/L: male) or abnormal age appropriate N terminalpro-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 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) if ALamyloidosis 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 dilatedcardiomyopathy)
• 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 singleterritory
• 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 poor candidatefor ultrasound therapy