International Journal of Molecular Sciences (Jan 2023)

Endothelial Dysfunction Drives CRTd Outcome at 1-Year Follow-Up: A Novel Role as Biomarker for miR-130a-5p

  • Celestino Sardu,
  • Gaetano Santulli,
  • Gianluigi Savarese,
  • Maria Consiglia Trotta,
  • Cosimo Sacra,
  • Matteo Santamaria,
  • Mario Volpicelli,
  • Antonio Ruocco,
  • Ciro Mauro,
  • Giuseppe Signoriello,
  • Lorenza Marfella,
  • Michele D’Amico,
  • Raffaele Marfella,
  • Giuseppe Paolisso

DOI
https://doi.org/10.3390/ijms24021510
Journal volume & issue
Vol. 24, no. 2
p. 1510

Abstract

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Endothelial dysfunction (ED) causes worse prognoses in heart failure (HF) patients treated with cardiac resynchronization therapy (CRTd). ED triggers the downregulation of microRNA-130 (miR-130a-5p), which targets endothelin-1 (ET-1). Thus, we evaluated ED and the response to CRTd by assessing miR-130a-5p and ET-1 serum levels. We designed a prospective multi-center study with a 1-year follow-up to evaluate ED, ET-1, and miR-130a-5p in CRTd patients with ED (ED-CRTd) vs. patients without ED (NED-CRTd). Clinical outcomes were CRTd response, HF hospitalization, cardiac death, and all-cause death. At 1-year follow-up, NED-CRTd (n = 541) vs. ED-CRTd (n = 326) patients showed better clinical statuses, lower serum values of B type natriuretic peptide (BNP: 266.25 ± 10.8 vs. 297.43 ± 16.22 pg/mL; p p p p p p < 0.05). Higher miR-130a-5p levels (HR 1.490, CI 95% [1.014–2.188]) significantly predicted CRTd response; the presence of hypertension (HR 0.818, CI 95% [0.669–0.999]), and displaying higher levels of ET-1 (HR 0.859, CI 98% [0.839–0.979]), lymphocytes (HR 0.820, CI 95% [0.758–0.987]), LVEF (HR 0.876, CI 95% [0.760–0.992]), and ED (HR 0.751, CI 95% [0.624–0.905]) predicted CRTd non-response. Higher serum miR-130a-5p levels (HR 0.332, CI 95% [0.347–0.804]) and use of ARNI (HR 0.319, CI 95% [0.310–0.572]) predicted lower risk of HF hospitalization, whereas hypertension (HR 1.818, CI 95% [1.720–2.907]), higher BNP levels (HR 1.210, CI 95% [1.000–1.401]), and presence of ED (HR 1.905, CI 95% [1.238–2.241]) predicted a higher risk of HF hospitalization. Hence, serum miR-130a-5p could identify different stages of ED and independently predict CRTd response, therefore representing a novel prognostic HF biomarker.

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