12/19/15

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Infiltrative Heart Diseases

Mary O. Gray, M.D. Professor of Medicine (Cardiology)

UC San Francisco

mary.gray@ucsf.edu

No Disclosures

Increased Left Ventricular Mass and Thick Walls

Hypertrophic Cardiomyopathy

Hypertension & Kidney Disease

Cardiac Amyloidosis

Mucopoly- Saccharidosis

Cardiac Sarcoidosis

Friedreich Ataxia

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Endomyocardial Biopsy: Alcian Blue

Pathophysiology and Treatment of Cardiac Amyloidosis

MA Gertz, A Dispenzieri, and T Sher Nature Reviews Cardiology 12, 91-102 (2015)

12/19/15

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Classification of Cardiac Amyloid Types

Amyloidosis Type Precursor Comment

Light Chain AL Immunoglobulin Light Chain Plasma Cell Dyscrasia

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

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Serum Free Light Chain Assay

Bone Marrow Biopsy: λ Light Chains

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Subcutaneous Fat Aspirate: Congo Red

Positive

Non-Ischemic Cardiomyopathy

Serum and Urine Immunofixation. Serum Free Light Chain Assay.

Bone Marrow Biopsy and Fat Aspiration with Congo Red Staining

AL Likely. Confirm with Mass Spectroscopy.

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Diagnosis, Prognosis, and Therapy of Transthyretin Amyloidosis

MA Gertz, MD Benson, PJ Dyck, et al. JACC 2015;66:2451-2466

12/19/15

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Transthyretin (TTR) Transporter of Thyroxine and Retinol

Positive

Non-Ischemic Cardiomyopathy

Serum and Urine Immunofixation. Serum Free Light Chain Assay.

Mass Spectroscopy and TTR Gene Sequencing

TTR Wild-Type or Mutant Fat Aspirate Endomyocardial Biopsy

Negative

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Evaluation to Diagnose TTR Amyloidosis

Results Suggestive of ATTR

✔ Physical Examination Autonomic Neuropathy

✔Serum Immunofixation and

Immunoglobulin Free LC Assay LC Amyloidosis Excluded

✔ Urine Tests Nephrotic Range Proteinuria

✔Tissue and Strain Doppler

Echocardiography Diastolic Dysfunction

✔ Cardiac Magnetic Resonance Chamber Infiltration

Results Suggestive of ATTR

✔ Radionuclide Imaging Cardiac Amyloid Detection

✔ Cardiac Biomarkers Elevated Troponin 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

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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

12/19/15

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CMR with Late Gadolinium Enhancement

LGE Pattern and Cardiac Amyloid Burden

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LGE Pattern and Cumulative Survival

Hypothesis: Cardiac Amyloid Progression

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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

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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

12/19/15

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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

12/19/15

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99mTechnetium Imaging of Wild-Type TTR Amyloid

Scintigraphy Scan

SPECT Imaging

Response to CPHC and Anti-SAP Antibody