AMYLOIDOSIS AND HEART€¦ · AMYLOIDOSIS OR AMYLOIDOSES? Various localisations –various clinical...
Transcript of AMYLOIDOSIS AND HEART€¦ · AMYLOIDOSIS OR AMYLOIDOSES? Various localisations –various clinical...
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AMYLOIDOSIS AND HEART
MATJAŽ KLEMENC
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AMYLOIDOSIS OR AMYLOIDOSES?
Various localisations – various clinical patterns
Multi organ disease, with a prognosis
driven by heart involvement
Mahmood et al: Hematologica 2014; 99(2): 209-221.
Wechalekar et al: The Lancet 2016; 387: 2641-53.
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AMYLOIDOSIS OR AMYLOIDOSIS ?
Various precursos = various types of amyloidosis
Mahmood et al: Hematologica 2014; 99(2): 209-221.
Wechalekar et al. The Lancet 2016; 387: 2641-53.
Transthyretin: a transport protein - thyroxine
and retinol , created in the liver
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AL AMYLOIDOSIS
• LC fibrils infiltrate the
myocardium,
• interfere with cell–cell coupling,
• disrupt cellular integrity
• and may contribute to cell injury
and death
• LC monomers also can elicit
oxidative damage by interacting
with proteins involved in cell
viability and metabolism
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AL AMYLOIDOSIS
• Sudden death in patients with AL amyloidosis is usually attributed
to:
• pulseless electrical activity → ventricular arrhythmias,
• thromboembolic complications
• bradyarrhythmias
• conduction system disease secondary to amyloid infiltration
• autonomic dysfunction
Grogan M, Dispenzieri A. Natural history and therapy
of AL cardiac amyloidosis. Heart Fail Rev 2015;20:155–62.
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CLUES TO DIAGNOSIS OF AL AMYLOIDOSIS
• heart failure associated with neuropathy
• nephrotic syndrome
• hepatomegaly
• periorbital bleeding
• macroglossia
symptoms of cardiac AL amyloidosis
may mimic those of other restrictive
cardiomyopathies
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CONFIRMATION OF DIAGNOSIS
• detection of amyloid in organ or other tissue biopsy using Congo red or
other histological staining
• cardiac biopsy conclusively identifies cardiac AL amyloidosis
• assessment of amyloid from periumbilical fat aspirates or from bone
marrow or labial salivary gland biopsy specimens is a less invasive
approach (sensitivity ≈ 80% in experienced centers)
• accurate amyloid typing* is critical because treatment of cardiac
amyloidosis depends entirely on amyloid type
*… gold standard of amyloid typing is
to determine the precursor protein using
laser microdissection mass spectrometry.
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ALGORITHM FOR DIAGNOSIS IN PATIENTS WITH SUSPECTED CARDIAC AMYLOIDOSIS
Gertz M et al, Nat Rev Cardiol 2015;12:91–102
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ALGORITHM FOR DIAGNOSIS IN PATIENTS WITH AMYLOIDOSIS ESTABLISHED BY BIOPSY
Gertz M et al, Nat Rev Cardiol 2015;12:91–102
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CONSENSUS CRITERIA FOR ORGAN INVOLVEMENT - HEART
• Diagnostic criteria*:
• mean LV wall thickness >12 mm in diastole on echocardiography (no other
cardiac cause)
• elevated NT-proBNP (>332 ng/L) in the absence of renal failure or atrial
fibrillation
*Non-invasive diagnostic criteria in patients for whom
a diagnosis of systemic amyloidosis has been made
by tissue biopsy; once the diagnosis of systemic
amyloidosis has been established, biopsy of organs to
determine extent of involvement is not recommended.
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STRUCTURE OF TTR AND FORMING OF FIBRILS
Ruberg: JACC 2019
hereditary ATTR-CM: mutation in the transthyretin gene, which
results in amyloid deposits in the heart, nerves and sometimes
the kidneys and other organs, symptoms may start as early as
age 20 or as late as age 80.
wild-type ATTR-CM: no mutation in the transthyretin gene,
most commonly affects the heart and can also cause carpal
tunnel syndrome and peripheral neuropathy (pain and
numbness in the hands and feet), symptoms usually start after
age 65.
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GENOTYPE - PHENOTYPE IN TTRA
“neurological” “cardiac”
phenotype
Rapezzi C in sod: European Heart Journal (2013) 34, 520–528
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COMPARISON OF CAUSES, CLINICAL PRESENTATION AND CLINICAL OUTCOME
Grogan M, et al. Heart2017;103:1065–1072
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ECG AND AMYLOIDOSIS
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CARDIAC CONSEQUENCES OF INFILTRATION
• MYOCARDIAL DEPOSITS:
• wall thickening
• diastolic +/- systolic dysfunction
• elevated troponin
HFpEF
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CARDIAC COSEQUENCES OF INFILTRATION
difuse segmental subendocardial
Leone O et al. Amyloid 2012; 19(2): 99-105
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CHANGES OF THE HEART BECAUSE OF INFILTRATION
• VALVULAR DEPOSITS:
• tricuspid regurgitation
• mitral regurgitation
• aortic stenosis (low
gradient)
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CHANGES OF THE HEART BECAUSE OF INFILTRATION
• MYOCARDIAL DEPOSITS:
• wall thickening
• diastolic +/- systolic dysfunction
• elevated troponin
• VALVULAR DEPOSITS:
• trikuspid regurgitation
• mitral regurgitaton
• aortic stenosis (low gradient)
• ATRIAL DEPOSITS:
• supraventricular arrhytmias
• PERICARDIAL DEPOSITS:
• pericardial effusion
• CONDUCTION SYSTEM:
• AV / bundle branch block
• CARDIAC DYSAUTONOMIA:
• postural hypotension
• INTRA-VASCULAR DEPOSITS:
• ischaemia, thrombosis
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DYSAUTONOMIA : CARDIOVASCULAR SYSTEM
Palma JA et al: CAR 2019
impaired baroreflex mediated
sympathetic activation
neurogenic orthostatic
hypotension
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MORPHOLOGICAL PRESENTATIONS
• wall thickening
• systolic dysfunction
• diastolic dysfunction
• damages of the valves
• CARDIAC ULTRASOUND:
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CARDIAC ULTRASOUND
SYSTOLE DIASTOLE
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GLOBAL LONGITUDINAL STRAIN (GLS)
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GLS AND AMYLOIDOSIS
HCM AL TTRA
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MORPHOLOGICAL PRESENTATION: CMR
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LGE – PSIR : CARDIAC AMYLOIDOSIS
Fontana M, Circulation 2015
Without LGE subendocardial transmural
PSIR: phase sensitive inversion recovery
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THROMBUS IN LEFT ATRIAL APPENDAGE
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MORPHOLOGICAL PRESENTATION
• SCINTIGRAPHY:
• myocardial uptake of bone tracer
• myocardial defect with MIBG (meta-iodobenzylguanidine)
• 11C-Pittsburgh B compound (N-[methyl-11C]2-(49-methylamino-phenyl)-6-
hydroxybenzothi-azole ) and florbetapir can specifically bind
cardiac amyloid and may be useful when combined with
structural and functional imaging assessments
• 99mTc-pyrophosphate (PYP) and 99m3,3di-phosphono-1, 2-
propanodicarboxylic acid (DPD) may be useful for identifying
ATTR amyloidosis
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MYOCARDIUM AT MICROSCOPY
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MYOCARDIUM UNDER POLARIZING MICROSCOPY
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TREATMENTS OF PATIENTS WITH CARDIAC AL AMYLOIDOSIS AND OUTCOME
Grogan M, et al. Heart2017;103:1065–1072
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CARDIAC SUPPORT THERAPIES
• Conventional medications: beta-blockers, angiotensin-converting
enzyme inhibitors and angiotensin receptor blockers, may contribute to
early mortality and worsening of symptoms 1
• Diuretics (loop diuretics and aldosterone receptor antagonists), in
addition to monitoring electrolytes and creatine, are predominant
supportive treatments 1
• LVAD → challenge: small LV cavities with thickened walls and coexisting
right ventricular dysfunction 2
• ICD have not been associated with survival benefit in patients with
cardiac AL amyloidosis in retrospective series 3
1…Grogan M, Dispenzieri A. Natural history and therapy of AL cardiac amyloidosis. Heart Fail Rev 2015;20:155–62.
2… Swiecicki PL et al. Left ventricular device implantation for advanced cardiac amyloidosis. J Heart Lung Transplant 2013;32:563–8.
3… Lin G, Dispenzieri A, Kyle R, et al. Implantable cardioverter defibrillators in patients with cardiac amyloidosis. J Cardiovasc
Electrophysiol 2013;24:793–8.
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TREATMENT OF TTRA
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TO RESUME
Diane Bodez: ESC congress Paris 2019