More%Than%Just%Coronary%ArteryDiseaseThomas%D.%GossiosCardiomyopathies%LaboratoryAUTH%1st%Cardiology%Department,%AHEPA%Hospital

First&presentation

� Male,&67&years&old� Present&condition• Typical&angina&at&rest.• Progressive&dyspnea&on&exertion.• No&history&of&syncope&or&palpitations.� Medical&history• Arterial&hypertension&(well&controlled&–&5&yrs).• Bilateral&carpal&tunnel&syndrome,&surgically&treated.• Benign&prostate&hypertrophy.� Previous&echo:&LVH,&likely&attributed&to&arterial

hypertension

Electrocardiogram

Coronary'Angiography

Discharge*recommendations

� Re1evaluation*of*symptoms*in*1*month.� 24h*Holter*recording� No*conduction*abnormalities*or*tachyarrhythmias� CMR*study*pending

*� Patient*lost*to*follow1up*for*1*year.

Re#admission

� Progressively1increasing1dyspnea,1NYHA1III� No1angina� NT1pro#BNP1levels13301pg/mL

CMR

Hematology*work.up

• ESR*10*mm• Normal*Hct• Normal*eGFR• Serum*Albumin/Globulin*ratio*2.5/1• Serum*protein*electrophoresis:*no

monoclonal• Serum*immunoglobulin*quantification:

normal• Urine*protein*(.),*Bence*Jones*(.)• Bone*marrow*aspiration*normal

L/R$catheterization$Myocardial$biopsy

150$mmHg

100$mmHg

50$mmHg

Histology)study

Histology)study

Immunohistology-study

� Severe-diffuse-amyloid-fibril-infiltration� Severe-myocyte-damage� Immunolabeling� Anti-TTR-positive� Anti;Kappa,-anti;Lamda,-anti;SAA,

anti;Apolipoprotein-A1-negative� TTR-exon-and-flanking-sequence-analysis,

compatible-with-wild;type-TTR-amyloid.-

Cardiac'amyloidosisType Protein Cardiac

involvementExtracardiacinvolvement

Median5survival

AL#amyloidosis Light#chainamyloid

40350% Renal,#liver,#softtissue,#neuropathy

8348#months

Hereditary#TTRamyloidosis

Variant#TTR(depending#onmutation)

Rare#to#90%(depending#onmutation)

Neuropathy Variable(dependence#fromliver#Tx)

Wild3type#TTRamyloidosis#(SSA)

Wild3typetransthyretin

Almost#invariable Carpal#tunnelsyndrome

738#years

Apolipoprotein#A1amyloidosis

ApoA1#variant Rare Renal Slowly#progressive

SAA#(secondary)amyloidosis

Serum#amyloid#A Rare Renal,#liver Good#prognosis

Atrial#amyloidosis Atrial#natriureticpeptide

Invariable None Unknownsignificance

Banypersad#SM,#et#al.#J#Am#Heart#Assoc.#2012;1(2):e000364.

Red$flags$for$amyloidcardiomyopathy

� Any$type$of$amyloid� Conduction$disease• Low$voltage$QRS$(50%$AL$vs$<25%$other$forms)• Echocardiographic$findings• Neuropathy

$� Wild$type$TTR• Age$>60$years• Male$predominance• Sporadic$disease• Carpal$tunnel$syndrome$(34%$in$excised$tissue$wildMtype$TTR+)• Hematologic$profile$incompatible$with$amyloid$(MGUS$5%$at$>$60

years)• 99mTcMDPD$scintigraphy$uptake$≈$100%$in$TTR$amyloid/25%$in$AL.

Flow%diagram%for%the%evaluation%of%a%patient%withsuspected%cardiac%amyloidosis.

Falk%R.%Circulation%2005;112:204782060%

Treatment(options� All(types(of(amyloid(cardiomyopathy• Heart(failure(treatment• Potential(PPM/ICD(implantation

� AL(amyloidosis• Chemotherapeutic(agents

� Familial(TTR(amyloidosis• Orthotopic/domino(liver(transplantation((favorable(for(neuropathy,

FAP(not(cardiomyopathy)• Diflunisal(–(NSAID(related(adverse(effects• Tafamidis(–(currently(indicated(for(FAP• ALNITTR01/02(–(RNA(silencing((phase(1(trial)• ISISITTRRx(–(oligonucleotide,(receptor(blockade((phase(1(trial)

� Senile(systemic(amyloidosis• ?

((Dungu(JN,(et(al.(Cardiac(transthyretin(amyloidosis.(Heart.(2012;98(21):1546I54.

Epigallocatechin-3-gallate

Kristen(AV,(et(al.(Green(tea(halts(progression(of(cardiac(transthyretin(amyloidosis:(an(observational(report.(Clin(Res(Cardiol.(2012;101(10):805F13