Objective The coexistence of wild-type transthyretin cardiac amyloidosis (ATTR) is common in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). However, the impact of ATTR and AS on the resultant AS-ATTR is unclear and poses diagnostic and management challenges. We therefore used a multicohort approach to evaluate myocardial structure, function, stress and damage by assessing age-related, afterload-related and amyloid-related remodelling on the resultant AS-ATTR phenotype.
Methods We compared four samples (n=583): 359 patients with AS, 107 with ATTR (97% Perugini grade 2), 36 with AS-ATTR (92% Perugini grade 2) and 81 age-matched and ethnicity-matched controls. 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy was used to diagnose amyloidosis (Perugini grade 1 was excluded). The primary end-point was NT-pro Brain Natriuretic Peptide (BNP) and secondary end-points related to myocardial structure, function and damage.
Results Compared with older age controls, the three disease cohorts had greater cardiac remodelling, worse function and elevated NT-proBNP/high-sensitivity Troponin-T (hsTnT). NT-proBNP was higher in AS-ATTR (2844 (1745, 4635) ng/dL) compared with AS (1294 (1077, 1554)ng/dL; p=0.002) and not significantly different to ATTR (3272 (2552, 4197) ng/dL; p=0.63). Diastology, hsTnT and prevalence of carpal tunnel syndrome were statistically similar between AS-ATTR and ATTR and higher than AS. The left ventricular mass indexed in AS-ATTR was lower than ATTR (139 (112, 167) in AS-ATTR was lower than ATTR (139 (112, 167) in AS-ATTR was lower than ATTR (139 (112, 167) vs 180 (167, 194) g; p=0.013) and non-significantly different to AS (120 (109, 130) g; p=0.179).
Conclusions The AS-ATTR phenotype likely reflects an early stage of amyloid infiltration, but the combined insult resembles ATTR. Even after treatment of AS, ATTR-specific therapy is therefore likely to be beneficial.
- aortic valve stenosis
- transcatheter aortic valve replacement
Data availability statement
No data are available.
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Contributors Conception and study design: KPP, PRS, CN, AAK, GL, TAT, JCM, JM, MF, JG, AK, PNH, ADH and TT. Data acquisition: KPP, PRS, CN, AAK, GJ, GT, RH, SW, TT, LC, JDG, PNH, MF, AK, NS, JN, SK, MO, MM and LM. Data analysis/interpretation: KPP, PRS, CN, AH, PNH, TAT, GL and JCM. Drafting manuscript: KPP, PRS, CN, AH, PNH, TAT, GL and JCM. Critical revision of manuscript: all authors. final approval of manuscript: all authors. All authors agree to be accountable for all aspects of this manuscript.
Funding KPP is supported by a British Heart Foundation Clinical Research Training Fellowships (FS/19/d8/34523) and has research grant from Edwards Lifesciences. PRS (FS/16/31/32185) and RH (FS/17/82/33322) are supported by British Heart Foundation Clinical Research Training Fellowships; TAT (FS/19/35/3434) and MF are supported by British Heart Foundation Intermediate fellowships. FP has received research support from Siemens Healthineers. MM has received grants and personal fees from Edwards Lifesciences and personal fees from Abbott Vascular. JCM and TAT are directly and indirectly supported by the UCLH and Barts NIHR Biomedical Research Units.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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