Prognostic impact of suspected cardiac amyloidosis in aortic stenosis patients referred for transcatheter aortic valve implantation

Abstract

Background The prevalence of cardiac amyloidosis (CA) and aortic stenosis (AS) both increase with age. Transcatheter aortic valve implantation (TAVI) expands the number of patients (P) eligible for treatment of AS, emphasizing the need to understand the prevalence of CA in AS and its prognostic associations. Echocardiography with speckle tracking has emerged as a useful method to enhance the clinical suspicion and to provide prognostic information. Purpose To estimate the prevalence of CA in P with severe AS referred for TAVI and to evaluate the impact of concomitant CA in prognosis. Methods 94 consecutive AS P who underwent TAVI with maximum left ventricular wall thickness (LVWT)>12 mm were retrospectively identified. Clinical data, pre TAVI echocardiographic parameters and follow up (FU) data regarding all-cause mortality and MACE (including all-cause mortality, admission for heart failure, pacemaker implantation and stroke) were analysed. We registered apical sparing pattern in bull's eye plots (ASPB), calculated relative apical longitudinal strain formula (RALS) [average apical LS/(average basal LS + mid-LS)] and ejection fraction/global longitudinal strain (EF/GLS) ratio. Results Mean age was 82.2±5.8 years (Y), with 43 men (45.7%). 27.7% were in NYHA functional class II, 64.9% in functional class III and 7.4% in functional class IV. Median EF was 57±15% and 26.6% presented EF<50%. Suspected CA evaluated by ASPB was found in 39 P (41.5%) and RALS >1 was identified in 22 P (23.4%). An EF/GLS ratio >4.1 was obtained in 53 P (56.4%). Over a median follow-up of 13.4±25.8 months, 28 deaths (29.8%) and 31 MACEs (33.0%) occurred. The presence of ASPB was associated with increased all-cause mortality (33.3% vs. 5.6%, p=0.002) and MACE (48.7% vs 22.2%, p=0.01). RALS>1 correlated also with all-cause mortality (31.8% vs. 12.5%, p=0.04) and with new bundle branch block and indication for pacemaker implantation (46.2% vs 37.0%, p=0.05). P with GLS>−14.8% and ASPB had significantly worse prognosis regarding all-cause mortality (p=0.003) and MACE (p=0.007). Kaplan–Meier survival analysis showed that survival was significantly worse for P with ASPB (log-rank 0.002). With multivariate Cox regression analysis, ASPB was independently associated with all-cause mortality (HR=4.49, p=0.039). Conclusions Suspected CA appears prevalent among patients with AS and associates with all-cause mortality. The importance of screening for CA in older AS patients and optimal treatment strategies in those with CA warrant further investigation, especially in the era of transcatheter aortic valve implantation. Funding Acknowledgement Type of funding source: None

Red Flags, Prognostic Impact, and Management of Patients With Cardiac Amyloidosis and Aortic Valve Stenosis: A Systematic Review and Meta-Analysis

“…The negative impact of CA on patients with AS was also confirmed when data were adjusted for publication bias. We confirmed that CA is associated to a worse prognosis in patients with AS even after a sensitivity analysis without the study including patients with only a probability of CA, based on echocardiographic strain analysis (19). Interestingly, the negative effect of CA on AS outcome appears to be reduced in older subjects, thus suggesting the importance of CA assessment especially in patients with AS younger than 80 years old.…”

“…The revision of full-length articles allowed the exclusion of fourteen studies due to wrong study design or irrelevant information in their content. Thus, seventeen studies ( 6 , 7 , 13 – 17 , 19 , 20 , 24 – 31 ), enrolling 1,988 subjects (1,658 AS alone and 330 AS with CA), were included in the qualitative and quantitative analyses of main patients with AS characteristics with and without CA (14 studies), difference in mortality (9 studies), and treatment strategy (10 studies).…”

“…The prevalence of CA was accessed in 14 studies ( 6 , 7 , 13 – 17 , 19 , 20 , 25 , 28 – 31 ), including 1,934 subjects (276 with concomitant CA and AS), resulting in a mean of 15.4%. Our results suggest that the prevalence of CA is lower in patients with AS under 80 years old compared with patients over 80 years old (7.1 vs. 18.2%, respectively).…”

“…Clinical and demographic characteristics as well as cardiovascular risk factors associated with CA prevalence in patients with AS were reported in 12 studies ( 6 , 7 , 13 , 15 – 17 , 19 , 20 , 28 – 31 ), including 1,772 subjects (1,506 AS alone and 266 AS with CA) ( Table 1 ; Supplementary Figures 1 , 2 ).…”

“…We included in the analysis only studies on patients with AS with suspected or confirmed CA at echocardiography, cardiac magnetic resonance (CMR), and bone scintigraphy. In particular, we included two echocardiographic studies that identified patients with concomitant CA and severe AS with apical sparing pattern at LV strain analysis ( 19 , 20 ). In each study, data regarding major clinical, demographic, echocardiographic, electrocardiographic variables, and prevalence of cardiovascular risk factors in patients with AS with and without CA were extracted.…”