Is Elevated Relaxin-2 a Marker for Poor Prognosis in HFpEF?

Elevated levels of circulating relaxin-2 in patients with chronic heart failure with preserved ejection fraction may indicate poor prognosis.

In chronic heart failure with preserved ejection fraction (HFpEF), higher circulating relaxin-2 may be a marker for adverse outcomes, according to results of a prospective cohort study published in the International Journal of Cardiology.

The NETDiamond (New Targets in Diastolic Heart Failure: From Comorbidities to Personalized Medicine) study is an ongoing study conducted at the Centro Hospitalar Universitário de São João in Portugal. In this analysis, relaxin-2 levels were evaluated among patients (N=85) with chronic HFpEF and 2-year outcomes were compared on the basis of circulating levels.

The patients had a median age of 77 (IQR, 69-81) years, 54% were men, and relaxin-2 concentration was 31.4 (range, 0.4-1572.7) pg/mL. Four patients had relaxin-2 levels below the detection limit.

Stratified by tertile, 29 patients had low (range, 0.4-17.67 pg/mL), 28 had intermediate (range, 18-32-62.1 pg/mL), and 28 had high (range, 65.4-1572.6 pg/mL) relaxin-2 concentrations. The tertile groups differed by the following patient characteristics:

  • History of coronary artery bypass graft (P <.001)
  • History of myocardial infarction (P =.004)
  • Phosphate levels (P =.005)
  • Uric acid levels (P =.015)
  • Urinary phosphate to creatinine ratio (P =.015)
  • Left ventricular mass index (P =.023)
  • Left atrial volume index (P =.024)
  • Use of statin medication (P =.022)
  • Rates of presenting with peripheral edema (P =.041)

After adjusting for cofounders, the highest tertile of relaxin-2 was at increased risk for the 2-year composite outcome of cardiovascular death, heart failure hospitalization, acute heart failure episode, and diuretic intensification (adjusted hazard ratio, 4.62; 95% CI, 1.21-8.90; P =.020) compared with the lowest tertile. Increased relaxin-2 was also associated with an increased rate of cardiovascular death and heart failure hospitalization (incident rate ratio, 5.28; 95% CI, 1.2-23.2; P =.027) compared with low relaxin-2.

This study is limited by the small sample size and by not having data from an independent cohort to confirm findings.

 “…our study suggests that relaxin-2 is a marker of poor outcome in chronic stable HFpEF,” the study authors wrote. “The validation of these results in larger HFpEF cohorts and the incorporation of relaxin-2 in multimarker prognostication models may be valuable to increase our knowledge on HFpEF pathophysiology and to improve these patients’ risk prediction.”


Pintalhão M, Vasques-Nóvoa F, Couto-Viana B, et al. Relaxin-2, pathophysiological insights and outcomes in heart failure with preserved ejection fraction: Findings from the NETDiamond cohort. Int J Cardiol. Published online July 20, 2022. doi:10.1016/j.ijcard.2022.07.037