The primary objective of this study is to define the intracardiac flow imaging biomarkers in cardiac amyloidosis.

Inclusion Criteria:

• Subject is clinically stable without cardio-vascular-related hospitalizations within 6 weeks prior to enrollment as assessed by the investigators.

• Subject is able to provide written informed consent and is willing and able to complete study procedures.

• Currently in sinus rhythm by clinical assessment or documented electrocardiographic studies.

• Subject and disease characteristics noted by medical record review:

  • Healthy control volunteers must also meet the following criteria: Karnofsky performance scale > 80%; ECOG status 0 or 1.
  • ATTR cardiac amyloidosis based on meeting all the following criteria: Diagnosis of amyloidosis within five years prior to study screening; Documentation of absence of AL, heavy chain disease, multiple myeloma or malignant lymphoproliferative disorders; Transthyretin amyloid deposits in cardiac tissue OR technetium (99mTc) pyrophosphate scintigraphy with grade 2 or 3 cardiac uptake OR Transthyretin amyloid deposits in non-cardiac tissue with echocardiographic evidence of cardiac involvement or an end-diastolic mean wall thickness >12mm OR Transthyretin amyloid deposits in non-cardiac tissue with CMR diagnostic of amyloidosis
  • AL with cardiac involvement based on meeting all the following criteria: Diagnosis of amyloidosis within five years prior to study screening; Histopathologic diagnosis of amyloidosis with AL protein identification; Documented clinical signs or symptoms consistent with heart failure; Cardiac involvement as defined by: Amyloid deposits in cardiac deposits OR Echocardiography with an end-diastolic mean wall thickness > 12 mm in the absence of other causes OR Elevated NT-proBNP (>332 ng/L) in the absence of renal failure or atrial fibrillation OR CMR diagnostic of amyloidosis;
  • AL without cardiac involvement based on meeting all the following criteria: Diagnosis of amyloidosis within five years prior to study screening; Histopathologic diagnosis of amyloidosis with AL protein identification; No documented clinical signs and symptoms consistent with heart failure from AL; Absence of cardiac involvement as defined by: Echocardiography with an end-diastolic mean wall thickness < 13 mm if the subject does not have other causes for increased wall thickness AND NT-proBNP <333 ng/L if the subject does not have renal failure or atrial fibrillation AND No CMR diagnostic of amyloidosis if CMR is available prior to screening.

Exclusion Criteria:

• Unable to consent or unable to complete all study procedures.

• Unable to ambulate for 6 minutes (confirmed at study coordinator visit).

• Unable to maintain in supine position for 30 minutes.

• Unable to maintain breath-holding for 10 seconds (confirmed at study coordinator visit).

• Contraindications for safe CMR scanning (e.g., uncontrolled claustrophobia, cochlear implant, implanted neural stimulator).

• Presence of implantable cardiac pacemaker or defibrillator.

• History of complex congenital heart disease, intracardiac shunt (except for patent foramen ovale), prosthetic valves, prosthesis in the main pulmonary artery or ascending thoracic aorta.

• Significant artifact from prior MRI studies.

• Pregnant or breast-feeding women.

• Weight equal to or greater than 155 kg.

• Maximum body side-to-side or anterior-posterior diameter equal to or greater than 70 cm.

• Documented non-sinus rhythm within 1 week prior to screening.

• For healthy controls, the following exclusion criteria apply, confirmed per chart review and/or patient report:

  • History of cardiomyopathy or structural heart disease;
  • History of valvular disease of greater than mild severity;
  • History of coronary artery disease or coronary heart disease;
  • History of cardiac or thoracic surgery.
  • History of symptomatic, persistent atrial tachyarrhythmia, ventricular tachyarrhythmia, or bradyarrhythmia;
  • Left ventricular hypertrophy or abnormally increased myocardial thickness by prior echocardiography, cardiac computed tomography, or CMR;
  • Acute kidney injury, OR chronic renal disease with glomerular filtration rate < 45 mL/min/1.73m^2 as per medical record review.
  • Uncontrolled hypertension of systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg as per medical record review;
  • Taking three or more anti-hypertensive medications;
  • Type 1 diabetes, OR uncontrolled type 2 diabetes mellitus of hemoglobin A1c greater than 8, as per medical record review;
  • Taking three or more diabetic medications;
  • History of confirmed stroke or transient ischemic attack, as per medical record review;
  • Current cigarette smoker;
  • History of plasma cell dyscrasia or chronic malignant hematologic diagnosis;
  • BMI > 35 kg/m^2.

Patients with amyloidosis without and with cardiac involvement, and normal healthy volunteers