Ultrasound Therapy In Cardiac Amyloidosis

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.

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