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Cardiac amyloidosis

Background

Overview

Definition
Cardiac amyloidosis refers to infiltration of the heart muscle by amyloid proteins, resulting in cardiomyopathy.
1
Pathophysiology
Cardiac amyloidosis is caused by extracellular accumulation of misfolded protein fragments (immunoglobulin light-chain and transthyretin protein) in the heart muscle.
1
Disease course
Clinical manifestations are related to the development of restrictive cardiomyopathy and include angina, myocardial infarction, and HF. An increased risk of thromboembolic complications is also present.
1
Prognosis and risk of recurrence
Unadjusted 5-year mortality rates are estimated at 65% in patients with AL cardiac amyloidosis and 44% in patients with ATTR cardiac amyloidosis.
2

Guidelines

Key sources

The following summarized guidelines for the evaluation and management of cardiac amyloidosis are prepared by our editorial team based on guidelines from the European Society of Cardiology (ESC 2023,2021), the Heart Failure Society of America (HFSA/AHA/ACC 2022), the Canadian Heart Failure Society (CHFS/CCS 2020), the American Heart Association (AHA/HRS/ACC 2019), the Amyloidosis Research Consortium (ARC 2019), and the Heart Rhythm ...
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Screening and diagnosis

Indications for testing: as per CCS/CHFS 2020 guidelines, obtain diagnostic workup for cardiac amyloidosis in patients presenting with signs and symptoms of HF having ≥ 1 of the following features:
unexplained increased LV wall thickness
> 60 years of age with low-flow low-gradient aortic stenosis and LVEF > 40%
unexplained peripheral sensorimotor neuropathy and/or dysautonomia
history of bilateral carpal tunnel syndrome
established light chain or transthyretin amyloidosis.
B
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Classification and risk stratification

Risk stratification: as per CCS/CHFS 2020 guidelines, use a validated serum biomarker-based staging system, including troponin and/or BNP/NT-proBNP, to risk-stratify patients with cardiac amyloidosis.
A

Diagnostic investigations

Clinical history: as per ARC 2019 guidelines, recognize the following history/examination diagnostic clues to ATTR cardiomyopathy:
evidence of right-sided HF (e.g., hepatomegaly, ascites, and lower extremity edema)
HFpEF, particularly in men
intolerance to ACE inhibitors or β-blockers
bilateral carpal tunnel syndrome
lumbar spinal stenosis
biceps tendon rupture
unexplained peripheral neuropathy (e.g., loss of warm/cold discrimination), particularly if associated with autonomic dysfunction (e.g., postural hypotension, alternating bowel pattern)
unexplained atrial arrhythmias or conduction system disease/need for a pacemaker.
E

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  • Testing for monoclonal protein

  • Evaluation for HF

  • Radionuclide imaging

  • ATTR genotyping

Diagnostic procedures

Endomyocardial biopsy: as per CCS/CHFS 2020 guidelines, perform endomyocardial biopsy for diagnosis and subtyping with mass spectrometry or immunohistochemistry/immunofluorescence, if available, when the existing diagnostic workup for cardiac amyloidosis is equivocal or discordant with clinical suspicion.
B

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  • Tissue biopsy

Medical management

General principles: as per CCS/CHFS 2020 guidelines, provide comprehensive interdisciplinary management in patients with established cardiac amyloidosis.
B

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  • Transthyretin tetramer stabilizer therapy

  • Anticoagulation therapy

  • Digoxin

Therapeutic procedures

ICD
As per HRS 2019 guidelines:
Place an ICD in patients with cardiac amyloidosis survived a cardiac arrest, if the expected meaningful survival is > 1 year.
B
Consider placing a prophylactic ICD in patients with AL-type cardiac amyloidosis with nonsustained ventricular arrhythmias, if the expected meaningful survival is > 1 year.
C

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  • Permanent cardiac pacing

  • Catheter ablation

Surgical interventions

Heart transplantation: as per CCS/CHFS 2020 guidelines, consider offering heart transplantation in selected patients with advanced HF due to cardiac amyloidosis if significant extracardiac manifestations are absent and the risk of disease progression is considered low and/or amenable to disease-modifying therapy.
B

Follow-up and surveillance

Indications for hematology referral: as per ARC 2019 guidelines, refer patients with a monoclonal protein to hematology.
E

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  • Imaging and laboratory follow-up