Heart Failure Reviews

, Volume 24, Issue 4, pp 521–533 | Cite as

Advances in the diagnosis and treatment of transthyretin amyloidosis with cardiac involvement

  • Angelos G. Rigopoulos
  • Muhammad Ali
  • Elena Abate
  • Abdel-Rahman Torky
  • Marios Matiakis
  • Mammad Mammadov
  • Hannes Melnyk
  • Alexander Vogt
  • Renato de Vecchis
  • Boris Bigalke
  • Walter Wohlgemuth
  • Sophie Mavrogeni
  • Michel NoutsiasEmail author


Amyloidosis is caused by extracellular deposition of insoluble abnormal fibrils constituted by misfolded proteins, which can modify tissue anatomy and hinder the function of multiple organs including the heart. Amyloidosis that can affect the heart includes mostly systemic amyloidosis (amyloid light chain, AL) and transthyretin amyloidosis (ATTR). The latter can be acquired in elderly patients (ATTRwt), or be inherited in younger individuals (ATTRm). The diagnosis is demanding given the high phenotypic heterogeneity of the disease. Therefore, “red flags,” which are suggestive features giving support to diagnostic suspicion, are extremely valuable. However, the lack of broad awareness among clinicians represents a major obstacle for early diagnosis and treatment of ATTR. Furthermore, recent implementation of noninvasive diagnostic techniques has revisited the need for endomyocardial biopsy (EMB). In fact, unlike AL amyloidosis, which requires tissue confirmation and typing for diagnosis, ATTR can now be diagnosed noninvasively with the combination of bone scintigraphy and the absence of a monoclonal protein. Securing the correct diagnosis is pivotal for the newly available therapeutic options targeting both ATTRm and ATTRwt, and are directed to either stabilization of the abnormal protein or the reduction of the production of transthyretin. The purpose of this article is to review the contemporary aspects of diagnosis and management of transthyretin amyloidosis with cardiac involvement, summarizing also the recent therapeutic advances with tafamidis, patisiran, and inotersen.


ATTR Cardiac amyloidosis Diagnosis Transthyretin Treatment 



Tc-99m-3,3-diphosphono-1,2-propanodicarboxylic acid


Tc-99m-hydroxymethylene diphosphonate






Light chain amyloidosis


Atrial natriuretic peptide


Aortic stenosis


Transthyretin amyloidosis


Mutant transthyretin amyloidosis


Wild-type transthyretin amyloidosis


Brain natriuretic peptide


Cardiac amyloidosis


Cardiac magnetic resonance


Cardiac troponin T




Endomyocardial biopsy


Ejection fraction


Ejection fraction strain ratio


Global longitudinal strain


Hypertrophic cardiomyopathy


Heart failure


Heart failure with preserved ejection fraction


Kansas City Cardiomyopathy Questionnaire-Overall Summary


Low-flow low-gradient


Late gadolinium enhancement


Left ventricular


Left ventricular hypertrophy


Left ventricular outflow tract

Norfolk QOL-DN

Norfolk Quality of Life-Diabetic Neuropathy


N-terminal pro-brain natriuretic peptide


Positron emission tomography


Retinol binding protein 4


Restrictive cardiomyopathy


Right ventricular


Sudden cardiac death




Transcatheter aortic valve implantation


Tissue Doppler imaging




Compliance with ethical standards

Conflict of interest

MN has received grants by the Deutsche Forschungsgemeinschaft through the Sonderforschungsbereich Transregio 19 “Inflammatory Cardiomyopathy” (SFB TR19) to MN (TP B2) and to CT (TP B5); and by the University Hospital Giessen and Marburg Foundation Grant “T cell functionality” (UKGM 10/2009). MN has been consultant to the IKDT (Institute for Cardiac Diagnosis and Therapy GmbH, Berlin) 2004–2008, and has received honoraria for presentations and/or participated in advisory boards from AstraZeneca, Bayer, Fresenius, Miltenyi Biotech, Novartis, Pfizer, and Zoll. AR has received honoraria for presentations from AstraZeneca. MA has received honoraria for presentations from AstraZeneca.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Angelos G. Rigopoulos
    • 1
  • Muhammad Ali
    • 1
  • Elena Abate
    • 1
  • Abdel-Rahman Torky
    • 1
  • Marios Matiakis
    • 1
  • Mammad Mammadov
    • 1
  • Hannes Melnyk
    • 1
  • Alexander Vogt
    • 1
  • Renato de Vecchis
    • 2
  • Boris Bigalke
    • 3
  • Walter Wohlgemuth
    • 4
  • Sophie Mavrogeni
    • 5
  • Michel Noutsias
    • 1
    Email author
  1. 1.Mid-German Heart Center, Department of Internal Medicine III (KIM-III), Division of Cardiology, Angiology and Intensive Medical Care, University Hospital HalleMartin-Luther-University HalleHalle (Saale)Germany
  2. 2.Preventive Cardiology and Rehabilitation Unit, DSB 29S. Gennaro dei Poveri HospitalNaplesItaly
  3. 3.Department of CardiologyCharité - Universitätsmedizin BerlinBerlinGermany
  4. 4.Department of Radiology, University Hospital HalleMartin-Luther-University HalleHalle (Saale)Germany
  5. 5.Onassis Cardiac Surgery CenterAthensGreece

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