12/19/15 Infiltrative Heart Diseases Mary O. Gray, M.D. Professor of Medicine (Cardiology) UC San Francisco [email protected] 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 .