Prevalence and Outcomes of Concomitant Aortic Stenosis and Cardiac Amyloidosis

Abstract

Background: Older patients with severe aortic stenosis (AS) are increasingly identified as having cardiac amyloidosis (CA). It is unknown whether concomitant AS-CA has worse outcomes or results in futility of transcatheter aortic valve replacement (TAVR).

Objectives: This study identified clinical characteristics and outcomes of AS-CA compared with lone AS.

Methods: Patients who were referred for TAVR at 3 international sites underwent blinded research core laboratory ^99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy (Perugini grade 0: negative; grades 1 to 3: increasingly positive) before intervention. Transthyretin-CA (ATTR) was diagnosed by DPD and absence of a clonal immunoglobulin, and light-chain CA (AL) was diagnosed via tissue biopsy. National registries captured all-cause mortality.

Results: A total of 407 patients (age 83.4 ± 6.5 years; 49.8% men) were recruited. DPD was positive in 48 patients (11.8%; grade 1: 3.9% [n = 16]; grade 2/3: 7.9% [n = 32]). AL was diagnosed in 1 patient with grade 1. Patients with grade 2/3 had worse functional capacity, biomarkers (N-terminal pro-brain natriuretic peptide and/or high-sensitivity troponin T), and biventricular remodeling. A clinical score (RAISE) that used left ventricular remodeling (hypertrophy/diastolic dysfunction), age, injury (high-sensitivity troponin T), systemic involvement, and electrical abnormalities (right bundle branch block/low voltages) was developed to predict the presence of AS-CA (area under the curve: 0.86; 95% confidence interval: 0.78 to 0.94; p < 0.001). Decisions by the heart team (DPD-blinded) resulted in TAVR (333 [81.6%]), surgical AVR (10 [2.5%]), or medical management (65 [15.9%]). After a median of 1.7 years, 23% of patients died. One-year mortality was worse in all patients with AS-CA (grade: 1 to 3) than those with lone AS (24.5% vs. 13.9%; p = 0.05). TAVR improved survival versus medical management; AS-CA survival post-TAVR did not differ from lone AS (p = 0.36).

Conclusions: Concomitant pathology of AS-CA is common in older patients with AS and can be predicted clinically. AS-CA has worse clinical presentation and a trend toward worse prognosis, unless treated. Therefore, TAVR should not be withheld in AS-CA.

Keywords: TAVR; aortic stenosis; cardiac amyloidosis.

Graphical abstract

Figure 1

Patient Population Patient population. AS = aortic stenosis; DPD = ^99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid; SAVR = surgical aortic valve replacement; TAVR = transcatheter aortic valve replacement.

Figure 2

Scoring System for the Discrimination of Lone AS and Dual Pathology AS-CA Scoring system for the discrimination of lone AS and dual pathology AS-CA. AFib = atrial fibrillation; AS = aortic stenosis; AUC = area under the curve; BBB = bundle branch block; CA = cardiac amyloidosis; CTS = carpal tunnel syndrome; Hs-TnT = high-sensitivity troponin T; IVS = interventricular septum; PM = pacemaker; RBBB = right bundle branch block; SR = sinus rhythm.

Figure 3

1-Year Mortality for Lone AS and AS-CA Patients with AS-CA experienced a trend toward higher all-cause mortality at 1 year in all patients referred for aortic valve replacement. Abbreviations as in Figure 2.

Figure 4

All-Cause Mortality in Lone AS Versus AS-CA Following Aortic Valve Replacement or With Medical Therapy Aortic valve replacement (AVR) improved outcomes for both lone AS and dual pathology AS-CA. Post-AVR survival of AS-CA was comparable to lone AS. Abbreviations as in Figure 2.

Central Illustration

Concomitant Pathology Aortic Stenosis-Cardiac Amyloidosis Concomitant pathology aortic stenosis-cardiac amyloidosis. PARTNER 1B data adapted from Kapadia et al. (20). AS = aortic stenosis; AVR = aortic valve replacement; CA = cardiac amyloidosis; DPD = ^99mtechnetium-3,3-diphosphono-1,2-propanodicarboxylic acid; RBBB = right bundle branch block; TAVR = transcatheter aortic valve replacement.