Infiltrative Heart Diseases Mary O. Gray, M.D. Professor of - - PDF document

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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)

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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

• f Transthyretin Amyloidosis

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

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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

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Physical Examination Autonomic Neuropathy

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Serum Immunofixation and Immunoglobulin Free LC Assay LC Amyloidosis Excluded

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Urine Tests Nephrotic Range Proteinuria

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Tissue and Strain Doppler Echocardiography Diastolic Dysfunction

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Cardiac Magnetic Resonance Chamber Infiltration

Results Suggestive of ATTR

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Radionuclide Imaging Cardiac Amyloid Detection

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Cardiac Biomarkers Elevated Troponin Brain Natriuretic Peptide

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Medical History Carpal Tunnel Syndrome

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Tissue Biopsy: less invasive Fat and Bone Marrow

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Tissue Biopsy: more invasive Heart, Nerve, Kidney

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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

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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

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Loop Diuretic Volume Status

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ACE Inhibitor or ARB Blood Pressure

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Beta Blocker Cardiac Output

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Calcium Channel Blocker Cardiac Output

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Arrhythmias and Cardiac Amyloidosis

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Amiodarone Effective

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Anticoagulation Effective

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Cardioverter-Defibrillator Possible Benefit

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Revascularization Possible Benefit

A European Collaborative Study of Cyclophosphamide, Bortezomib, and Dexamethasone in Upfront Treatment

• f Systemic AL Amyloidosis

G Palladini, S Sachchithanantham, et al. Blood 2015;126(5):612-615

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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

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99mTechnetium Imaging of Wild-Type TTR Amyloid

Scintigraphy Scan SPECT Imaging

Response to CPHC and Anti-SAP Antibody