Aortic Valve Stenosis and Cardiac Amyloidosis: A Misleading Association

Abstract

The association between aortic stenosis (AS) and cardiac amyloidosis (CA) is more frequent than expected. Albeit rare, CA, particularly the transthyretin (ATTR) form, is commonly found in elderly people. ATTR-CA is also the most prevalent form in patients with AS. These conditions share pathophysiological, clinical and imaging findings, making the diagnostic process very challenging. To date, a multiparametric evaluation is suggested in order to detect patients with both AS and CA and choose the best therapeutic option. Given the accuracy of modern non-invasive techniques (i.e., bone scintigraphy), early diagnosis of CA is possible. Flow-charts with the main CA findings which may help clinicians in the diagnostic process have been proposed. The prognostic impact of the combination of AS and CA is not fully known; however, new available specific treatments of ATTR-CA have changed the natural history of the disease and have some impact on the decision-making process for the management of AS. Hence the relevance of detecting these two conditions when simultaneously present. The specific features helping the detection of AS-CA association are discussed in this review, focusing on the shared pathophysiological characteristics and the common clinical and imaging hallmarks.

Keywords: amyloidosis; aortic valve stenosis; multimodality imaging; transthyretin amyloidosis.

Figure 1

Pathophysiologic correlation between aortic stenosis and cardiac amyloidosis. See the text for details.

Figure 2

Red flags of cardiac amyloidosis (CA). (A–E) Typical echocardiographic features of CA. (A) Left ventricle (LV) short-axis slices obtained from a 3D dataset showing severe LV hypertrophy and myocardial granular sparkling. (B) 4-Chamber view and parasternal long-axis showing an increase of left and right ventricular walls thickness, left atrial dilatation, atrial septal thickening and pericardial effusion. (C) Pulsed wave Doppler of the mitral valve inflow reveals restrictive filling pattern (grade III diastolic dysfunction) with marked reduced lateral mitral annular diastolic velocity (e′ 4.8 cm/sec at the tissue Doppler analysis); tissue Doppler signals from the lateral mitral annulus shows longitudinal systolic dysfunction with mitral Sʹ ≤ 6 cm/s. (D) Speckle tracking imaging showing a depressed LV global longitudinal strain (−12%) with apical sparing and an apex/basal longitudinal strain ratio > 2. (E) Focused right ventricle (RV) view showing RV wall thickening (≥5 mm). (F–I) Typical cardiac magnetic resonance (CMR) features of CA. (F) Steady-state free precession sequences (SSFP) showing diffuse and asymmetric hypertrophy of the LV and RV. (G) T1-mapping reveals prolongation of the native relaxation time and of the extracellular volume (ECV). (H) Typical late gadolimium enhancement (LGE) pattern: LGE is extensive and circumferential, starts from the subendocardium and predominates at the basal segments with a base-to-apex gradient in a non-ischemic pattern; sub-optimal nulling of myocardium is present, and the blood pool has a signal darker than the myocardium; LGE is also evident in the RV wall, atria walls and atrial septum. (I) Frames from Look–Locker inversion recovery sequences (T1 scout) showing altered gadolinium kinetics in ATTR-CA: evidence of reverse order of sequences with the myocardium passing through the null-point before the blood pool. (J) Typical ECG findings of CA: discordance between low-voltage and LV wall thickness; discordance between the voltages in peripheral and precordial leads; pseudo-infarction pattern (Q waves) without history of myocardial infarction; right axis deviation; abnormal P wave duration and morphology reflecting slow atrial conduction. (K) ^99mTc-hydroxymethylene diphosphonate scintigraphy showing strong cardiac uptake (Perugini Grade 2).

Figure 3

Diagnostic flow-chart and red flags to recognize cardiac amyloidosis involvement in AS patients. See the text for details. Legend—AF: atrial fibrillation; AS: aortic stenosis; DPD: 99mTc-3,3-diphosphono-1,2-propanodicarboxylic-acid; EMB: endomyocardial biopsy; GLS: global longitudinal strain; HF—heart failure; HMDP: 99mTc-hydroxymethylene diphosphonate; LFLG: low-flow low-gradient; LGE: late gadolinium enhancement; LV: left ventricle; Nt-proBNP: N-terminal pro-brain natriuretic peptide; PYP:99mTc-pyrophosphate, SAVR: surgical aortic valve replacement; TAVR: transcatheter aortic valve replacement.