Diagnosing cardiac amyloidosis in every-day practice: A practical guide for the cardiologist

Abstract

Cardiac amyloidosis (CA) has emerged as a previously underestimated cause of heart failure and mortality. Underdiagnosis resulted mainly from unawareness of the true disease prevalence and the non-specific symptoms of the disease. CA results from extracellular deposition of misfolded protein fibrils, commonly derived from transthyretin (ATTR) or immunoglobulin light chains (AL). A significant proportion of older patients with heart failure and other extracardiac manifestations suffer from ATTR-CA, whereas AL-CA is still considered a rare disease. This article provides an overview of CA with a special focus on current and emerging diagnostic modalities. Furthermore, we provide a diagnostic algorithm for the evaluation of patients with suspected CA in every-day practice.

Keywords: 99mTc-DPD, 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid; AA, amyloid A amyloidosis; AApoA-1, apolipoprotein A-1 amyloidosis; AL, light chain amyloidosis; ATTR, transthyretin amyloidosis; ATTRv, variant transthyretin amyloidosis; ATTRwt, wild type transthyretin amyloidosis; Amyloidosis; CA, cardiac amyloidosis; Cardiomyopathy; ECV, Extracellular volume; EMB, endomyocardial biopsy; Heart failure; LGE, late gadolinium enhancement; LV, left ventricular/ left ventricular; Light chains; MGUS, monoclonal gammopathy of undetermined significance; MRI, magnetic resonance imaging; NT-proBNP, N-terminal pro B-type natriuretic peptide; PET, positron-emission tomography; SPECT, single photon emission computed tomography; Transthyretin.

Fig. 1

Echocardiographic presentation of patients with cardiac amyloidosis: Parasternal long axis, apical four chamber and subcostal view from a patient with ATTRv-CA Marked left and right ventricular hypertrophy with speckled myocardial appearance are present, as well as pericardial effusion. (A-C). Pulsed wave doppler of the mitral valve inflow reveals restrictive filling pattern with marked reduction in mitral annular early diastolic velocity (e′ 5.4 cm/sec) in a patient with ATTRwt-CA (D, E). F: Global longitudinal strain of the patient with ATTRwt-CA is significantly reduced (−10.4%) with characteristic sparing of the strain values in apical segments (F).

Fig. 2

Cardiac MRI depicting concentric LV hypertrophy and diffuse transmural LGE in a patient with ATTRwt-CA. (A, B). ^99mTc-DPD planar scintigraphy with grade 3 myocardial tracer uptake (C).

Fig. 3

Integrated ¹⁸F-Flutemetamol PET/MRI in a patient with ATTRv-CA. The patient had known ATTRv with polyneuropathy under treatment with tafamidis and presented with new onset dyspnea. T1 mapping revealed prolongation of relaxation time (A). Subendocardial late gadolinium enhancement was present (B). PET images showed ¹⁸F-Flutemetamol uptake of the left and right ventricle, indicative of advanced stage myocardial amyloid infiltration (C).

Fig. 4

Proposed algorithm for the diagnostic evaluation of patients with suspected cardiac amyloidosis.