Abstract
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.
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Abbreviations
- [99mTc]-DPD:
-
Tc-99m-3,3-diphosphono-1,2-propanodicarboxylic acid
- [99mTc]-HMDP:
-
Tc-99m-hydroxymethylene diphosphonate
- [99mTc]-PYP:
-
Tc-99m-pyrophosphate
- 123I-MIBG:
-
123I-Metaiodobenzylguanidine
- AL:
-
Light chain amyloidosis
- ANP:
-
Atrial natriuretic peptide
- AS:
-
Aortic stenosis
- ATTR:
-
Transthyretin amyloidosis
- ATTRm:
-
Mutant transthyretin amyloidosis
- ATTRwt:
-
Wild-type transthyretin amyloidosis
- BNP:
-
Brain natriuretic peptide
- CA:
-
Cardiac amyloidosis
- CMR:
-
Cardiac magnetic resonance
- cTnT:
-
Cardiac troponin T
- ECG:
-
Electrocardiography
- EMB:
-
Endomyocardial biopsy
- EF:
-
Ejection fraction
- EFSR:
-
Ejection fraction strain ratio
- GLS:
-
Global longitudinal strain
- HCM:
-
Hypertrophic cardiomyopathy
- HF:
-
Heart failure
- HFpEF:
-
Heart failure with preserved ejection fraction
- KCCQ-OS:
-
Kansas City Cardiomyopathy Questionnaire-Overall Summary
- LFLG:
-
Low-flow low-gradient
- LGE:
-
Late gadolinium enhancement
- LV:
-
Left ventricular
- LVH:
-
Left ventricular hypertrophy
- LVOT:
-
Left ventricular outflow tract
- Norfolk QOL-DN:
-
Norfolk Quality of Life-Diabetic Neuropathy
- NT-proBNP:
-
N-terminal pro-brain natriuretic peptide
- PET:
-
Positron emission tomography
- RBP4:
-
Retinol binding protein 4
- RCM:
-
Restrictive cardiomyopathy
- RV:
-
Right ventricular
- SCD:
-
Sudden cardiac death
- ST:
-
Speckle-tracking
- TAVI:
-
Transcatheter aortic valve implantation
- TDI:
-
Tissue Doppler imaging
- TTR:
-
Transthyretin
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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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Rigopoulos, A.G., Ali, M., Abate, E. et al. Advances in the diagnosis and treatment of transthyretin amyloidosis with cardiac involvement. Heart Fail Rev 24, 521–533 (2019). https://doi.org/10.1007/s10741-019-09776-3
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DOI: https://doi.org/10.1007/s10741-019-09776-3