Circulating Progenitor Cells Are Associated With Bioprosthetic Aortic Valve Deterioration: A Preliminary Study

Yoshihisa Kanaji, Ilke Ozcan, Takumi Toya, Rajiv Gulati, Melissa Young, Tsunekazu Kakuta, Lilach O. Lerman, Amir Lerman

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Mechanisms underlying bioprosthetic valve deterioration are multifactorial and incompletely elucidated. Reparative circulating progenitor cells, and conversely calcification-associated osteocalcin expressing circulating progenitor cells, have been linked to native aortic valve deterioration. However, their role in bioprosthetic valve deterioration remains elu-sive. This study sought to evaluate the contribution of different subpopulations of circulating progenitor cells in bioprosthetic valve deterioration. METHODS AND RESULTS: This single-center prospective study enrolled 121 patients who had peripheral blood mononuclear cells isolated before bioprosthetic aortic valve replacement and had an echocardiographic follow-up ≥2 years after the proce-dure. Using flow cytometry, fresh peripheral blood mononuclear cells were analyzed for the surface markers CD34, CD133, and osteocalcin. Bioprosthetic valve deterioration was evaluated by hemodynamic valve deterioration (HVD) using echocar-diography, which was defined as an elevated mean transprosthetic gradient ≥30 mm Hg or at least moderate intraprosthetic regurgitation. Sixteen patients (13.2%) developed HVD during follow-up for a median of 5.9 years. Patients with HVD showed significantly lower levels of reparative CD34+ CD133+ cells and higher levels of osteocalcin-positive cells than those without HVD (CD34+ CD133+ cells: 125 [80, 210] versus 270 [130, 420], P=0.002; osteocalcin-positive cells: 3060 [523, 5528] versus 670 [180, 1930], P=0.005 respectively). Decreased level of CD34+ CD133+ cells was a significant predictor of HVD (hazard ratio, 0.995 [95% CI, 0.990%– 0.999%]). CONCLUSIONS: Circulating levels of CD34+ CD133+ cells and osteocalcin-positive cells were significantly associated with the subsequent occurrence of HVD in patients undergoing bioprosthetic aortic valve replacement. Circulating progenitor cells might play a vital role in the mechanism, risk stratification, and a potential therapeutic target for patients with bioprosthetic valve deterioration.

Original languageEnglish (US)
Article numbere027364
JournalJournal of the American Heart Association
Issue number2
StatePublished - Jan 17 2023


  • aortic valve stenosis
  • bioprosthetic valve deterioration
  • circulating progenitor cells
  • structural valve degeneration
  • valve replacement

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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