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Original research
Impact of afterload and infiltration on coexisting aortic stenosis and transthyretin amyloidosis
  1. Kush P Patel1,2,
  2. Paul Richard Scully1,2,
  3. Christian Nitsche3,
  4. Andreas A Kammerlander4,
  5. George Joy5,
  6. George Thornton1,5,
  7. Rebecca Hughes1,5,
  8. Suzanne Williams6,
  9. Therese Tillin6,
  10. Gabriella Captur1,6,
  11. Liza Chacko7,
  12. Andrew Kelion8,
  13. Nikant Sabharwal8,
  14. James D Newton8,
  15. Simon Kennon2,
  16. Mick Ozkor2,
  17. Michael Mullen2,
  18. Philip N Hawkins7,
  19. Julian D Gillmore7,
  20. Leon Menezes2,
  21. Francesca Pugliese2,9,
  22. Alun D Hughes6,
  23. Marianna Fontana7,
  24. Guy Lloyd2,
  25. Thomas A Treibel1,2,
  26. Julia Mascherbauer4,
  27. James C Moon1,2
  1. 1Institute of Cardiovascular Science, University College London, London, UK
  2. 2Department of Cardiology, Barts Heart Centre, London, UK
  3. 3Department of Internal Medicine, Medical University of Vienna, Wien, Austria
  4. 4Department of Cardiology, Medical University of Vienna, Vienna, Austria
  5. 5Cardiac Imaging Department, Barts Heart Centre, London, UK
  6. 6MRC Unit for Lifelong Health and Ageing, London, UK
  7. 7National Amyloidosis Centre, London, UK
  8. 8Department of Cardiology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
  9. 9Advanced Cardiovascular Imaging, William Harvey Research Institute, The London Chest Hospital, London, UK
  1. Correspondence to Dr Kush P Patel, Department of Cardiology, Barts Heart Centre, London EC1A 7BE, UK; kush.p.patel04{at}gmail.com

Abstract

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) 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
  • cardiomyopathy
  • restrictive

Data availability statement

No data are available.

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Footnotes

  • Correction notice This article has been corrected since it was first published. Duplications of a sentence in the Abstract were removed and the headings in Figure 2 were updated to be consistent with the main text.

  • 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.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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