diagnosis in amyloidosis - :// · both attrv and attrwt amyloidosis are systemic diseases al and...

Guard

UMCG

Workshop B: Optimizing diagnosis and patient care in ATTR amyloid cardiomyopathy Current standards of care for patients with ATTR cardiomyopathy

Bouke P.C. Hazenberg

UMC Groningen

The Netherlands

UMC Groningen – Rheumatology & Clinical Immunology

Guard UMC Groningen – Rheumatology & Clinical Immunology UMCG

Financial support

From Alnylam as clinical consultant

From Pfizer as clinical consultant

As external scientific advisor GSK

Disclosures

Guard UMC Groningen – Rheumatology & Clinical Immunology UMCG UMCG

ATTR amyloidosis: a systemic disease

ATTRv

Autosomal dominant hereditary disease

Clinical manifestations:

Polyneuropathy, autonomic neuropathy, CTS

Cardiomyopathy

Ocular: vitreous opacities, retinal vascular abnormalities

Leptomeningeal/cerebrovascular deposition

ATTRwt

Men>women, >60jr

Clinical manifestations:

Cardiomyopathy

CTS, lumbar spinal stenosis

Tendon ruptures, soft tissue and joint deposition

Lung and kidney involvement


Case 1, Mrs. A. Progressive heart failure: NYHA III (walk 25 meters, edema, ascites)

Echo: wall thickness 15 mm

Rectal biopsy: amyloid, but unable to type using immunohistochemistry

NT-proBNP 2347 (N<125), TnT 21 (N,15)

No FLCs, no M-protein, and bone marrow: no clonal plasma cells

Gene analysis: no TTR mutation


What amyloid type do you consider? What would you investigate?

HMDP-Bone scan: cardiac uptake grade 1 SAP scan: liver and spleen uptake


Types of amyloidosis with cardiomyopathy

Dubrey and Comenzo. Q J Med 2012; 105:617-31

Note added: Gelsolin (AGel) can cause conduction problems


Bone scan in Apo A-I en Apo A-II amyloidosis

Bone scan 99mTc-DPD or 99mTC-PYP positive (grade 1-3): ApoA-I Q172P variant1

ApoA-I Leu174Ser variant2

ApoA-II Stop78Arg variant3

Conclusion Case 1: Uncle hoarse voice, known with amyloidosis Gene panel: ApoA-I Leu178Pro variant4

1. Vonberg et al, Amyloid 2015; 22:252-3

2. Quarta, et al. Amyloid 2013: 20:48-51

3. Yazaki, et al. Kidney Int 2003; 64:11-6

4. Hazenberg, et al. Laryngoscope 2009; 119:608-15


Case 2, Mr. A. Black man

Cardiac failure NYHA II

NT-proBNP 4400, TnT 160, creat 90

Echo wall thickness 15 mm, MRI late gadolinium enhancement

Fat aspirate: amyloid (2+)

M-protein IgG-kappa, BJ kappa, FLC kappa

Bone marrow: small kappa-positive plasma cell clone

What would you investigate?


HMDP-Bone scan: cardiac uptake grade 3 SAP scan: little liver uptake

Case 2, Mr. A.


ATTR amyloidose

Gillmore, et al. Circulation 2016; 133:2404-12


Case 2, Mr. A. Gene panel: TTR Val122Ile mutation present

Fat aspirate: Amyloid TTR +, kappa negative

Endomyocardial biopsy: TTR +, kappa non-specific

Liver biopsy: no amyloid

Conclusion: ATTRv (Val122Ile) amyloidosis

However …


Extremely rare1 Two types of amyloid in a single heart: ATTR and AL-lambda

Anti-TTR sample Y

Anti-lambda sample X

Congo red

1. Mahmood, et al. Blood 2014; 124:3025-7


Key learnings and recommendations

Both ATTRv and ATTRwt amyloidosis are systemic diseases

AL and ATTR amyloidosis are the main causes of amyloid cardiomyopathy, but do not overlook rarer

types, such as AA, AFib, AANF, AApoAI, and AApoAII

A negative bone scan does not exclude amyloid cardiomyopathy. If serious doubt: consider a biopsy

A positive bone scan is not specific for ATTR type: consider first AL, then rarer: AApoAI and AApoAII

M-protein, serum free light chains, urine BJ, gene panel amyloidosis, bone scan and endomyocardial

biopsy are essential elements for detecting and typing of cardiac amyloidosis


www.amyloid.nl

diagnosis in amyloidosis - :// · both attrv and attrwt amyloidosis are systemic diseases al and...

Documents