Light-chain and transthyretin cardiac amyloidosis in severe aortic stenosis: prevalence, screening possibilities, and outcome

Abstract

Aims: Concomitant cardiac amyloidosis (CA) in severe aortic stenosis (AS) is difficult to recognize, since both conditions are associated with concentric left ventricular thickening. We aimed to assess type, frequency, screening parameters, and prognostic implications of CA in AS.

Methods and results: A total of 191 consecutive AS patients (81.2 ± 7.4 years; 50.3% female) scheduled for transcatheter aortic valve replacement (TAVR) were prospectively enrolled. Overall, 81.7% underwent complete assessment including echocardiography with strain analysis, electrocardiography (ECG), cardiac magnetic resonance imaging (CMR), ^99m Tc-DPD scintigraphy, serum and urine free light chain measurement, and myocardial biopsy in immunoglobulin light chain (AL)-CA. Voltage/mass ratio (VMR; Sokolow-Lyon index on ECG/left ventricular mass index) and stroke volume index (SVi) were tested as screening parameters. Receiver operating characteristic curve, binary logistic regression, and Kaplan-Meier curve analyses were performed. CA was found in 8.4% of patients (n = 16); 15 had transthyretin (TTR)-CA and one AL-CA. While global longitudinal strain by echo did not reliably differentiate AS from CA-AS [area under the curve (AUC) 0.643], VMR as well as SVi showed good discriminative power (AUC 0.770 and 0.773, respectively), which was comparable to extracellular volume by CMR (AUC 0.756). Also, VMR and SVi were independently associated with CA by multivariate logistic regression analysis (P = 0.016 and P = 0.027, respectively). CA did not significantly affect survival 15.3 ± 7.9 months after TAVR (P = 0.972).

Conclusion: Both TTR- and AL-CA can accompany severe AS. Parameters solely based on ECG and echocardiography allow for the identification of the majority of CA-AS. In the present cohort, CA did not significantly worsen prognosis 15.3 months after TAVR.

Keywords: Aortic stenosis; Cardiac amyloidosis; Prognosis; Screening; Transcatheter aortic valve replacement.

Figure 1

Patient population: 238 patients scheduled for transcatheter aortic valve replacement (TAVR) were screened. Reasons for exclusion and screening modalities are displayed. AS, aortic stenosis; CA, cardiac amyloidosis; CMR, cardiac magnetic resonance; ^99mTc‐DPD, ^99mTc‐labelled 3,3‐diphosphono‐1,2‐propanodicarboxylic‐acid scintigraphy; echo, transthoracic echocardiography.

Figure 2

Stroke volume index (SVi) and voltage/mass ratio (VMR) for the discrimination of aortic stenosis with/without cardiac amyloidosis. SVi as well as VMR showed good discriminative power for the distinction of aortic stenosis with/without cardiac amyloidosis. AUC, area under the curve; MCF, myocardial contraction fraction; MR‐ECV, extracellular volume by cardiac magnetic resonance.

Figure 3

Kaplan–Meier curves of patients with aortic stenosis (AS) with/without cardiac amyloidosis (CA). Concomitant cardiac amyloidosis (CA‐AS) was not associated with all‐cause mortality (A) or cardiovascular (CV) hospitalization (B) over 15.3 ± 7.9 months following transcatheter aortic valve replacement. One CA‐AS patient died prior to transcatheter aortic valve replacement and was therefore excluded from outcome analysis.