start date: August 31, 2023
estimated completion: June 30, 2025
last updated: December 7, 2023
phase of development:
Phase 4
size / enrollment: 70
study 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.
primary outcomes:
- Myocardial Blood Flow
N-13 ammonia or Rubidium-82 PET based measure of myocardial blood flow in ml/gm/min
- 1 day
Systolic Function
Global Longitudinal Strain by echocardiography
- 1 day
Diastolic Function
Echo measured mitral e' velocity
- 1 day
inclusion criteria:
• Eligible Ages: 18 - 90
• Eligible Sexes: all
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: 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 CMR
Implantable Cardioverter Defibrillator (ICD)
Significant renal dysfunction with estimated glomerular filtration rate < 30 ml/min/m2.
Dialysis
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