Transthyretin cardiac amyloidosis: an update on diagnosis and treatment

Abstract

Transthyretin cardiac amyloidosis (ATTR-CA) demonstrates progressive, potentially fatal, and infiltrative cardiomyopathy caused by extracellular deposition of transthyretin-derived insoluble amyloid fibrils in the myocardium. Two distinct types of transthyretin (wild type or variant) become unstable, and misfolding forms aggregate, resulting in amyloid fibrils. ATTR-CA, which has previously been underrecognized and considered to be rare, has been increasingly recognized as a cause of heart failure with preserved ejection fraction among elderly persons. With the advanced technology, the diagnostic tools have been improving for cardiac amyloidosis. Recently, the efficacy of several disease-modifying agents focusing on the amyloidogenic process has been demonstrated. ATTR-CA has been changing from incurable to treatable. Nevertheless, there are still no prognostic improvements due to diagnostic delay or misdiagnosis because of phenotypic heterogeneity and co-morbidities. Thus, it is crucial for clinicians to be aware of this clinical entity for early diagnosis and proper treatment. In this mini-review, we focus on recent advances in diagnosis and treatment of ATTR-CA.

Keywords: Amyloidosis; Cardiomyopathy; Diagnosis; Disease-modifying agents; Heart failure; Red-flags; Transthyretin.

Figure 1

Red‐flags that should be highly suspected of transthyretin cardiac amyloidosis. ACE‐I, angiotensin‐converting enzyme inhibitor; ARB, angiotensin II receptor blocker; CCB, calcium‐channel blocker; CMR, cardiac magnetic resonance; ECG, electrocardiogram; Echo, echocardiogram; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; LGE, late gadolinium enhancement; LV, left ventricle.

Figure 2

Diagnostic algorithm for patients with suspected cardiac amyloidosis. −, negative test; +, positive test; ^99mTc‐PYP, technetium pyrophosphate; AL‐CA, light‐chain cardiac amyloidosis; ATTR‐CA, transthyretin cardiac amyloidosis; ATTRv, hereditary transthyretin amyloidosis; ATTRwt, wild type transthyretin amyloidosis; CA, cardiac amyloidosis; CMR, cardiovascular magnetic resonance; EM, electron microscopy; IHC, immunohistochemistry; LMD/MS, Laser microdissection and mass spectrometry; sFLC, serum‐free light chain; sIFE, serum immunofixation electrophoresis; uIFE, urine immunofixation electrophoresis.