12/19/15
Infiltrative Heart Diseases
Mary O. Gray, M.D. Professor of Medicine (Cardiology) UC San Francisco
No Disclosures
Increased Left Ventricular Mass and Thick Walls
Hypertrophic Hypertension & Cardiomyopathy Kidney Disease
Cardiac Mucopoly- Amyloidosis Saccharidosis
Cardiac Friedreich Sarcoidosis Ataxia
1 12/19/15
Endomyocardial Biopsy: Alcian Blue
Pathophysiology and Treatment of Cardiac Amyloidosis
MA Gertz, A Dispenzieri, and T Sher Nature Reviews Cardiology 12, 91-102 (2015)
2 12/19/15
Classification of Cardiac Amyloid Types
Amyloidosis Type Precursor Comment
Immunoglobulin Light Chain AL Plasma Cell Dyscrasia Light Chain
Mutant Transthyretin TTR Point Mutation Autosomal Dominant
Wild-Type Transthyretin None Senile Amyloidosis
Amyloid A Serum Amyloid A Sustained Inflammation
Isolated Atrial Amyloid Atrial Natriuretic Factor Atrial Fibrillation
3 12/19/15
Serum Free Light Chain Assay
Bone Marrow Biopsy: λ Light Chains
4 12/19/15
Subcutaneous Fat Aspirate: Congo Red
Non-Ischemic Cardiomyopathy
Serum and Urine Immunofixation. Serum Free Light Chain Assay.
Bone Marrow Biopsy and Fat Aspiration with Congo Red Staining
Positive
AL Likely. Confirm with Mass Spectroscopy.
5 12/19/15
Diagnosis, Prognosis, and Therapy of Transthyretin Amyloidosis
MA Gertz, MD Benson, PJ Dyck, et al. JACC 2015;66:2451-2466
6 12/19/15
Transthyretin (TTR) Transporter of Thyroxine and Retinol
Non-Ischemic Cardiomyopathy
Serum and Urine Immunofixation. Serum Free Light Chain Assay.
Negative
TTR Wild-Type or Mutant Fat Aspirate Endomyocardial Biopsy
Positive
Mass Spectroscopy and TTR Gene Sequencing
7 12/19/15
Evaluation to Diagnose TTR Amyloidosis
Results Suggestive of ATTR
✔ Physical Examination Autonomic Neuropathy
Serum Immunofixation and LC Amyloidosis Excluded ✔ Immunoglobulin Free LC Assay
✔ Urine Tests Nephrotic Range Proteinuria
Tissue and Strain Doppler Diastolic Dysfunction ✔ Echocardiography
✔ Cardiac Magnetic Resonance Chamber Infiltration
Results Suggestive of ATTR
✔ Radionuclide Imaging Cardiac Amyloid Detection
Elevated Troponin Cardiac Biomarkers ✔ Brain Natriuretic Peptide
✔ Medical History Carpal Tunnel Syndrome
✔ Tissue Biopsy: less invasive Fat and Bone Marrow
✔ Tissue Biopsy: more invasive Heart, Nerve, Kidney
✔ Mass Spectroscopy TTR Amyloid Deposits
8 12/19/15
CMR without Gadolinium: Wall Thickening
Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis
M Fontana, S Pica, P Reant, et al. Circulation 2015;132:1570-1579
9 12/19/15
CMR with Late Gadolinium Enhancement
LGE Pattern and Cardiac Amyloid Burden
10 12/19/15
LGE Pattern and Cumulative Survival
Hypothesis: Cardiac Amyloid Progression
11 12/19/15
Heart Failure with Preserved Ejection Fraction
HFpEF Therapy and Cardiac Amyloidosis
✔ Loop Diuretic Volume Status
✔ ACE Inhibitor or ARB Blood Pressure
✔ Beta Blocker Cardiac Output
✔ Calcium Channel Blocker Cardiac Output
12 12/19/15
Arrhythmias and Cardiac Amyloidosis
✔ Amiodarone Effective
✔ Anticoagulation Effective
✔ Cardioverter-Defibrillator Possible Benefit
✔ Revascularization Possible Benefit
A European Collaborative Study of Cyclophosphamide, Bortezomib, and Dexamethasone in Upfront Treatment of Systemic AL Amyloidosis
G Palladini, S Sachchithanantham, et al. Blood 2015;126(5):612-615
13 12/19/15
AL Cardiac Stage and Survival after CyBorD
Therapeutic Clearance of Amyloid by Antibodies to Amyloid P Component
DB Richards, LM Cookson, AC Berges, et al. NEJM 2015;373:1106-1114
14 12/19/15
99mTechnetium Imaging of Wild-Type TTR Amyloid
Scintigraphy Scan
SPECT Imaging
Response to CPHC and Anti-SAP Antibody
15