Upload
drucsamal
View
286
Download
1
Embed Size (px)
Citation preview
Cardiac Amyloidosis: A Diagnostic Algorithm
Mazen Hanna, M.D.
Director, Heart Failure Intensive Care Unit Co-Director, Amyloid Program
Cleveland Clinic
March 15,2015
Amyloidosis Type Precursor protein Cardiac involvement
Prognosis
AL (Primary) Light chain 30-50% Poor if untreated
SSA (“Senile cardiac ) TTR (Transthyretin)
100% 5-7 yrs
ATTR (hereditary) Mutant TTR Mutation dependent
variable
AA (Reactive) Amyloid A < 5-10% 2 yrs
AANF (Isolated Atrial) Atrial natiuretic factor
Limited to atria …..
Cardiac amyloid
How common is TTR-CM?
• In the US, V122I is believed to occur heterogeneously in 3.5% of the African–American population
• SSA is not uncommon in the elderly population – ~ 25% pts > 80 yrs have wild type TTR amyloid deposits in
myocardium
– ~ 20% HFPEF in the elderly population
Ruberg FL, Maurer MS, Judge DP, et al. Am Heart J 2012;164:222–228; Buxbaum JN and Tagoe. Ann Rev Med 2000;51:543–569; Dungu JN, Andersen LJ, Whelan CJ et al. J Heart 2012;98:1146–1154.
Presentation
• CHF with predominant R sided sx’s
• Heart failure with preserved EF (HFPEF)
• Atrial fibrillation / cardioembolic stroke
• Pacemaker / Complete heart block
• Angina w normal cors
• Nephrotic syndrome
• Orthostasis
• Neuropathy
• Macroglossia or periorbital purpura (AL)
• Bilateral carpal tunnel syndrome (TTR)
Diagnostic Approach
Clinical + Echo + ECG
Endomyocardial biopsy
Serum free light chains
Serum immunofixation
Urine immunofixation
SPEP/UPEP
ĸ or ּת light chains
Heme/Onc Consult
Transthyretin
Genetic testing
Mutant TTR Wild Type
Cardiac MRI
Technetium
pyrophosphate scan
Echo w/ Strain
Laboratory Testing
• SPEP and UPEP
• Serum free light chain assay (Kappa/Lambda)
• Serum immunofixation
• Urine immunofixation
The Serum Free-Light Chain Assay - An Abnormal Ratio Proves a Clonal Plasma Cell Disorder - Useful for Diagnosis, Prognosis, Response Assessment
Dispenzieri et al. Leukemia 23, 215–224, 2009
Principle Immune - Nephelopmetry
Diagnosis Cardiac Amyloid by MRI
– There is accumulation of Gadolinium in areas of extracellular fibrosis/protein infiltration, due to increased volume of distribution and slower washout kinetics
Vogelsburg et al. JACC 2008;51:1022-30
80 % sensitivity
90% specificity
85% negative predictive value
Technetium pyrophosphate scan
Bokhari, Circ Cardiovasc Imaging. 2013;6:195-201.)
Specificity is very good Sensitivity for earlier disease is unknown
TTR allele 1: Sequence alteration detected: transition G ---> A Nucleotide position: 7356 Codon position: 122 Amino acid change: valine --> isoleucine
V122I
Genetic testing for TTR mutation
Heart transplant 2008 Doing well 7 years out
Onset of Disease in Patients with Cardiac Mutations or Wild Type TTR Amyloidosis
50
Ile68Leu N = 11
Leu111Met N = 10
Thr60Ala N = 11
WT N = 74
Val122Ile N = 29
RED FLAGS
• White age > 70 yrs with – “LVH” +/ - relative low voltage ECG
– Conduction disease/ pacemaker
– h/o Bilateral carpal tunnel syndrome
• AA > 65 yrs – “LVH”
• +/- relative low voltage ECG
• Out of proportion to valve disease/ HTN
– Family history CHF
RED FLAGS
• Elderly patient with HOCM (white male) – Echo with strain may help
– Need high index of suspicion TTR - CM
• Elderly patient with aortic stenosis or HTN – LVH “out of proportion”
– Gradient or clinical picture doesn’t entirely fit
– ECG may or may not help
– Need high index of suspicion
Pearls
• High index of suspcion
– ECG and ECHO
• Noninvasive testing can be helpful (strain, technetium pyrophosphate scan)
• DO NOT ORDER SPEP/UPEP!!!!!!!!!!!
• Wild type TTR (“senile”)
– h/o carpal tunnel syndrome, bilateral
• African Americans, TTR, V122I variant
AL TTR
Serum free light chains
Serum immunofixation
Urine immunofixation
Technetium pyrophosphate scan
ECHO with strain
Endomyocardial biopsy
Cardiac MRI
ECG