Prevalence and outcome of dual aortic stenosis and cardiac amyloid pathology in patients referred for transcatheter aortic valve implantation

Abstract

Aims: Cardiac amyloidosis is common in elderly patients with aortic stenosis (AS) referred for transcatheter aortic valve implantation (TAVI). We hypothesized that patients with dual aortic stenosis and cardiac amyloid pathology (AS-amyloid) would have different baseline characteristics, periprocedural and mortality outcomes.

Methods and results: Patients aged ≥75 with severe AS referred for TAVI at two sites underwent blinded bone scintigraphy prior to intervention (Perugini Grade 0 negative, 1-3 increasingly positive). Baseline assessment included echocardiography, electrocardiogram (ECG), blood tests, 6-min walk test, and health questionnaire, with periprocedural complications and mortality follow-up. Two hundred patients were recruited (aged 85 ± 5 years, 50% male). AS-amyloid was found in 26 (13%): 8 Grade 1, 18 Grade 2. AS-amyloid patients were older (88 ± 5 vs. 85 ± 5 years, P = 0.001), with reduced quality of life (EQ-5D-5L 50 vs. 65, P = 0.04). Left ventricular wall thickness was higher (14 mm vs. 13 mm, P = 0.02), ECG voltages lower (Sokolow-Lyon 1.9 ± 0.7 vs. 2.5 ± 0.9 mV, P = 0.03) with lower voltage/mass ratio (0.017 vs. 0.025 mV/g/m2, P = 0.03). High-sensitivity troponin T and N-terminal pro-brain natriuretic peptide were higher (41 vs. 21 ng/L, P < 0.001; 3702 vs. 1254 ng/L, P = 0.001). Gender, comorbidities, 6-min walk distance, AS severity, prevalence of disproportionate hypertrophy, and post-TAVI complication rates (38% vs. 35%, P = 0.82) were the same. At a median follow-up of 19 (10-27) months, there was no mortality difference (P = 0.71). Transcatheter aortic valve implantation significantly improved outcome in the overall population (P < 0.001) and in those with AS-amyloid (P = 0.03).

Conclusions: AS-amyloid is common and differs from lone AS. Transcatheter aortic valve implantation significantly improved outcome in AS-amyloid, while periprocedural complications and mortality were similar to lone AS, suggesting that TAVI should not be denied to patients with AS-amyloid.

Keywords: Aortic stenosis; Cardiac amyloidosis; TAVI.

Figure 1

A 90-year-old man with severe aortic stenosis referred for transcatheter aortic valve implantation. Apical four-chamber echocardiography (A) shows normal biventricular size with mild left ventricular hypertrophy (1.3 cm basal septum). Continuous-wave Doppler confirmed severe aortic stenosis (peak velocity > 4 m/s) (B). The ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid fused single-photon emission computed tomography/computed tomography short-axis (C) confirms diffuse cardiac retention of tracer, visible also on the planar image (D), compatible with Perugini grade 2.

Figure 2

Box and whisker plots demonstrating elevated high-sensitivity troponin T (A) and N-terminal pro-brain natriuretic peptide (B) in AS-amyloid compared to lone aortic stenosis and with amyloid burden measured by ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid Perugini grade. Outliers with an high-sensitivity troponin T greater than 200 ng/L and an N-terminal pro-brain natriuretic peptide greater than 150 000 have been excluded from this figure, but included in the statistical analysis (n = 2 and n = 4, respectively). HsTnT, high-sensitivity troponin T; NT-proBNP, N-terminal pro-brain natriuretic peptide.

Figure 3

Kaplan–Meier survival curves over a median follow-up of 19 months (interquartile range 10–27 months) by lone AS vs. AS-amyloid (P = 0.71) (A) and by management strategy (P = 0.03 for transcatheter aortic valve implantation vs. medical management in AS-amyloid, P < 0.001 for Transcatheter aortic valve implantation vs. medical management in lone AS, P = 0.48 in the post-transcatheter aortic valve implantation arm for AS-amyloid vs. lone AS and P = 0.39 in the medical management arm for AS-amyloid vs. lone AS) (B).

Take home figure

Bone scintigraphy was added to routine clinical care in 200 patients aged 75 and over referred for transcatheter aortic valve implantation with aortic stenosis. The prevalence of dual pathology (AS-amyloid) was confirmed as 13% and was associated with a higher N-terminal pro-brain natriuretic peptide and high-sensitivity troponin T than lone aortic stenosis, however, there was no difference in periprocedural complications or mortality. Furthermore, transcatheter aortic valve implantation significantly improved outcome in patients with AS-amyloid. AS, aortic stenosis; DPD, ^99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid; hsTnT, high-sensitivity troponin T; NT-proBNP, N-terminal pro-brain natriuretic peptide; TAVI, transcatheter aortic valve implantation.