Multimodality Imaging in the Evaluation and Prognostication of Cardiac Amyloidosis

Abstract

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy resulting from deposition of misfolded immunoglobulin light chains (AL-CA) or transthyretin (ATTR-CA) proteins in the myocardium. Survival varies between the different subtypes of amyloidosis and degree of cardiac involvement, but accurate diagnosis is essential to ensure initiation of therapeutic interventions that may slow or potentially prevent morbidity and mortality in these patients. As there are now effective treatment options for CA, identifying underlying disease pathogenesis is crucial and can be guided by multimodality imaging techniques such as echocardiography, magnetic resonance imaging, and nuclear scanning modalities. However, as use of cardiac imaging is becoming more widespread, understanding optimal applications and potential shortcomings is increasingly important. Additionally, certain imaging modalities can provide prognostic information and may affect treatment planning. In patients whom imaging remains non-diagnostic, tissue biopsy, specifically endomyocardial biopsy, continues to play an essential role and can facilitate accurate and timely diagnosis such that appropriate treatment can be started. In this review, we examine the multimodality imaging approach to the diagnosis of CA with particular emphasis on the prognostic utility and limitations of each imaging modality. We also discuss how imaging can guide the decision to pursue tissue biopsy for timely diagnosis of CA.

Keywords: cardiac amyloidosis; cardiac magnetic resonance imaging (CMR); cardiac scintigraphy; echocardiography; endomyocardial biopsy; nuclear imaging.

FIGURE 1

Proposed algorithm for diagnosis of cardiac amyloidosis. Algorithm for patients being assessed for cardiac amyloidosis based on heart failure or risk factors for AL or ATTR-CA. EMBx, endomyocardial biopsy; CMR, cardiac magnetic resonance imaging; LVH, left ventricular hypertrophy; SIFE, serum protein electrophoresis with immunofixation; TTE, transthoracic echocardiogram; UIFE, urine protein electrophoresis with immunofixation.

FIGURE 2

A Venn diagram comparing echocardiogram (echo) and cardiac magnetic resonance (CMR) characteristics seen in cardiac amyloidosis. ECV, extra cellular volume; EF, ejection fraction; FAC, fractional area change; GLS, global longitudinal strain; LGE, late gadolinium enhancement; LV, left ventricle; LVEDD, left ventricular end diastolic diameter; LVEDVi, left ventricular end diastolic volume index; LVH, left ventricular hypertrophy; LVMI, left ventricle mass index; MAPSE, mitral annular plane systolic excursion; MV, mitral valve; nl, normal; RV, right ventricle; TAPSE, tricuspid annular plane systolic excursion.

FIGURE 3

Representative echocardiographic images from a patient with cardiac amyloidosis. (A) Apical 4-chamber view showing moderate concentric left ventricular hypertrophy with more prominent proximal septal hypertrophy, significant bi-atrial enlargement, and diffusely thickened atrioventricular valves. (B) Parasternal long axis view showing large pleural effusion, moderate concentric hypertrophy, small left ventricular end diastolic diameter (LVEDD), and right ventricle outflow track dilation. (C) Subcostal view demonstrating significant right ventricular hypertrophy, biatrial enlargement, and interatrial septal thickening.

FIGURE 4

Doppler and longitudinal strain abnormalities in patients diagnosed with cardiac amyloidosis. (A) Mitral inflow and mitral annular tissue Doppler showing pseudonormal diastolic filling (Grade 2) and high E/e′ signaling elevated left atrial pressures. (B) Mitral inflow pulse wave Doppler of patient in atrial fibrillation demonstrating short deceleration time (DT) (normal 130–220 ms). (C) Peak systolic longitudinal strain map demonstrating reduced longitudinal strain in basal and mid ventricular segments with relative apical sparing.

FIGURE 5

Representative cardiac magnetic resonance images (CMR) from patients with cardiac amyloidosis. (A) T2 TRUFI 4-chamber view showing biventricular hypertrophy, biatrial enlargement, and pericardial effusion. (B) T1 4-chamber view late post-contrast image in a patient with ATTR-CA showing diffuse atrial LGE (arrowheads) and left ventricular subendocardial LGE (arrows). (C) T1 short-axis late post-contrast image in a patient with AL-CA showing diffuse LGE of the left ventricle.

FIGURE 6

Example results of pyrophosphate (PYP) scan in two patients diagnosed with ATTR-CA. (A) Grade 1 (negative) scan with (B) H/CL = 1.4 in a patient later diagnosed by endomyocardial biopsy. (C) Grade 3 (positive) PYP scan with (D) H/CL = 2.26.

FIGURE 7

Endomyocardial biopsy pathology in a patient with cardiac amyloidosis. Congo red stain at 10×x magnification showing apple-green birefringence under polarized light consistent with amyloid deposition.