Clonal hematopoiesis confers an increased mortality risk in orthotopic heart transplant recipients

Scolari F. L., Brahmbhatt D. H., Abelson S., Medeiros J. J. F., Anker M. S., Fung N. L., ...Daha Fazla

American Journal of Transplantation, cilt.22, sa.12, ss.3078-3086, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 22 Sayı: 12
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1111/ajt.17172
  • Dergi Adı: American Journal of Transplantation
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, PASCAL, CAB Abstracts, EMBASE, MEDLINE, Public Affairs Index, Veterinary Science Database
  • Sayfa Sayıları: ss.3078-3086
  • Anahtar Kelimeler: basic (laboratory) research, science, biomarker, clinical research, practice, genomics, heart transplantation, cardiology, molecular biology
  • TED Üniversitesi Adresli: Hayır

Özet

© 2022 The American Society of Transplantation and the American Society of Transplant Surgeons.Novel risk stratification and non-invasive surveillance methods are needed in orthotopic heart transplant (OHT) to reduce morbidity and mortality post-transplant. Clonal hematopoiesis (CH) refers to the acquisition of specific gene mutations in hematopoietic stem cells linked to enhanced inflammation and worse cardiovascular outcomes. The purpose of this study was to investigate the association between CH and OHT. Blood samples were collected from 127 OHT recipients. Error-corrected sequencing was used to detect CH-associated mutations. We evaluated the association between CH and acute cellular rejection, CMV infection, cardiac allograft vasculopathy (CAV), malignancies, and survival. CH mutations were detected in 26 (20.5%) patients, mostly in DNMT3A, ASXL1, and TET2. Patients with CH showed a higher frequency of CAV grade 2 or 3 (0% vs. 18%, p <.001). Moreover, a higher mortality rate was observed in patients with CH (11 [42%] vs. 15 [15%], p =.008) with an adjusted hazard ratio of 2.9 (95% CI, 1.4–6.3; p =.003). CH was not associated with acute cellular rejection, CMV infection or malignancies. The prevalence of CH in OHT recipients is higher than previously reported for the general population of the same age group, with an associated higher prevalence of CAV and mortality.