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Practical recommendations for the diagnosis and management of transthyretin cardiac amyloidosis

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Abstract

Cardiac amyloidosis (CA) is an infiltrative restrictive cardiomyopathy caused by accumulation in the heart interstitium of amyloid fibrils formed by misfolded proteins. Most common CA types are light chain amyloidosis (AL) caused by monoclonal immunoglobulin light chains and transthyretin amyloidosis (ATTR) caused by either mutated or wild-type transthyretin aggregates. Previously considered a rare disease, CA is increasingly recognized among patients who may be misdiagnosed as undifferentiated heart failure with preserved ejection fraction (HFPEF), paradoxical low-flow/low-gradient aortic stenosis, or otherwise unexplained left ventricular hypertrophy. Progress in diagnosis has been due to the refinement of cardiac echocardiographic techniques (speckle tracking imaging) and magnetic resonance (T1 mapping) and mostly due to the advent of bone scintigraphy that has enabled noninvasive diagnosis of ATTR, limiting the need for endomyocardial biopsy. Importantly, proper management of CA starts from early recognition of suspected cases among high prevalence populations, followed by advanced diagnostic evaluation to confirm diagnosis and typing, preferentially in experienced amyloidosis centers. Differentiating ATTR from other types of amyloidosis, especially AL, is critical. Emerging targeted ATTR therapies offer the potential to improve outcomes of these patients previously treated only palliatively.

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Authors and Affiliations

  1. Department of Cardiology, Heart Failure Unit, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece

    Vasiliki Bistola & John Parissis

  2. Cardiology Department, Venizeleion General Hospital of Heraklion, Heraklion, Greece

    Emmanouil Foukarakis

  3. Nuclear Medicine Department, “Alexandra” University General Hospital, Athens, Greece

    Pipitsa N. Valsamaki

  4. Unit of Inherited and Rare Cardiovascular Diseases, Onassis Cardiac Surgery Center, Athens, Greece

    Aris Anastasakis

  5. Neurogenetics Unit, 1st Department of Neurology, National and Kapodistrian University of Athens, Eginition University Hospital, Athens, Greece

    Georgios Koutsis

  6. 1st Cardiology Department, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Georgios Efthimiadis

  7. Department of Clinical Therapeutics, National and Kapodistrian University of Athens, Athens, Greece

    Efstathios Kastritis

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Dr. Bistola reports honoraria for lectures from Novartis, Pfizer, and Servier. Dr. Parissis reports horonaria for lectures and advisory boards from Novartis, Pfizer, Servier, Orion Pharma, and Roche Diagnostics. Dr. Kastritis has received honoraria for lectures and advisory boards from Amgen, Genesis Pharma, Janssen, Takeda, Pfizer, and research funding from Amgen and Janssen. Dr. Foukarakis reports honoraria for lectures and advisory boards from Pfizer, Menarini and Bayer. G. Koutsis has received research grants from Genesis Pharma and Teva, consultation fees, advisory boards, and honoraria from Genzyme, Genesis Pharma, Teva, and Novartis. Drs. Valsamaki, Anastasakis, and Efthimiadis report honoraria from Pfizer.

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Bistola, V., Parissis, J., Foukarakis, E. et al. Practical recommendations for the diagnosis and management of transthyretin cardiac amyloidosis. Heart Fail Rev 26, 861–879 (2021). https://doi.org/10.1007/s10741-020-10062-w

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