Concomitant Transthyretin Amyloidosis and Severe Aortic Stenosis in Elderly Indian Population

Abstract

Background Prevalence of both degenerative severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR-CA) increases with age. Dual disease (AS+myocardial ATTR-CA) occurs in significant proportion of patients undergoing surgical aortic valve replacement (SAVR). Objectives This study aimed to determine the prevalence of ATTR-CA in severe AS in the Indian population, identify noninvasive predictors of its diagnosis, and understand its impact on prognosis. Methods Symptomatic severe AS patients aged ≥65 years undergoing SAVR were enrolled. ATTR-CA diagnosis was based on preoperative 99m-technetium pyrophosphate (PYP) scan and intraoperatively obtained basal interventricular septum biopsy for myocardial ATTR-CA, and excised native aortic valve for isolated valvular ATTR-CA. Primary amyloidosis was excluded by serum/urine protein electrophoresis with serum immunofixation. Results SAVR was performed in 46 AS patients (age 70 ± 5 years, 70% men). PYP scan was performed for 32 patients, with significant PYP uptake in 3 (n = 3 of 32, 9.4%), suggestive of myocardial ATTR-CA. On histopathological examination, none of the interventricular septum biopsy specimens had amyloid deposits, whereas 33 (71.7%) native aortic valves showed amyloid deposits, of which 19 (57.6%) had transthyretin deposition suggestive of isolated valvular amyloidosis. Noninvasive markers of dual disease included low myocardial contraction fraction (median [interquartile range], 28.8% [23.8% to 39.1%] vs 15.3% [9.3% to 16.1%]; P = 0.006), deceleration time (215 [144 to 236] ms vs 88 [60 to 106] ms; P = 0.009) and global longitudinal strain (-18.7% [-21.1% to -16.9%] vs -14.2% [-17.0% to -9.7%]; P = 0.030). At 1-year follow-up, 2 patients died (4.3%); 1 each in myocardial ATTR-CA negative and positive groups (3.4% vs 33.3%; P = 0.477). Conclusions Dual disease is not uncommon in India. Isolated valvular amyloidosis in severe AS is much more common.

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

“…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 ).…”

“…The presence of CA was associated with an increased mortality rate in patients with AS. Nine studies ( 6 , 13 – 17 , 19 , 25 , 31 ) showed higher overall mortality in the 178 patients with AS with CA in comparison with 1,220 patients with AS alone with an OR of 2.25 (95% CI: 1.23–3.94, p = 0.004), with a moderate heterogeneity among studies ( I 2 : 43% p = 0.082; Figure 3 ).…”

“…Sensitivity analysis showed that, excluding the study of Ferreira et al ( 19 ), due to different methods of CA evaluation, considering eight studies ( 6 , 13 – 17 , 25 , 31 ) including 139 patients with AS with CA and 1,170 patients with AS without CA, the results were confirmed with an OR of 1.83 (95% CI: 1.11, 3.03, p = 0.019), without low heterogeneity among studies ( I 2 : 26% p = 0.219).…”