Ultrasound Therapy In Cardiac Amyloidosis

Prior treatment

• 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
• Prior cardiac surgery
• Any other reason determined by the investigator that makes a subject a poor candidate for ultrasound therapy

Other illness

• Decompensated heart failure (unable to lie flat for 1 hour)
• Severe pulmonary artery hypertension
• Severe lung disease
• Known obstructive epicardial coronary artery disease with stenosis \> 50% in any single territory
• 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

Lab values

• Left ventricular ejection fraction \< 40%
• 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

Other

• Hemodynamic instability
• Severe claustrophobia despite use of sedatives
• Regional wall motion abnormality on echocardiogram
• Pregnant state

• 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