Renal Dysfunction in Heart Failure With Preserved Ejection Fraction: Insights From the RELAX Trial: Renal Dysfunction in RELAX

RAVI B. Patel, RUPAL MEHTA, MARGARET M. REDFIELD, BARRY A. BORLAUG, ADRIAN F. HERNANDEZ, SANJIV J. SHAH, RUTH F. DUBIN

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Patients with heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) represent a high-risk phenotype. The Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial enrolled a high proportion of CKD participants, allowing investigation into differences in HFpEF by CKD status. Methods and Results: Among 212 participants, we investigated the associations of CKD with biomarkers, cardiac structure, and exercise capacity, and identified predictors of change in estimated glomerular filtration rate (eGFR) over trial follow-up. CKD participants (eGFR ≤60 mL/min/1.73m2) were older, had more comorbidities, and had worse diastolic function. Lower eGFR was associated with higher levels of endothelin-1, N-terminal pro–B-type natriuretic peptide, aldosterone, uric acid, and biomarkers of fibrosis (P < .05 for all). Whereas lower eGFR was associated with worse peak oxygen consumption (VO2) after adjustment for demographics, clinical comorbidities, exercise modality, ejection fraction, and chronotropic index (β coefficient per 1 SD decrease in eGFR: −0.61, 95% CI: −1.01, −0.22, P = .002), this association was attenuated after further adjustment for hemoglobin (β coefficient: −0.26, 95% CI: −0.68, 0.16, P = .22). Hemoglobin mediated 35% of the association between eGFR and peak VO2. Sildenafil therapy was independently associated with worsening eGFR over the trial (β coefficient: −2.79, 95% CI: −5.34, −0.24, P = .03). Conclusion: Renal dysfunction in HFpEF is characterized by echocardiographic and biomarker profiles indicative of more advanced disease, and reduced hemoglobin is a strong mediator of the association between renal dysfunction and low exercise capacity. Sildenafil therapy was associated with worsening of renal function in RELAX.

Original languageEnglish (US)
Pages (from-to)233-242
Number of pages10
JournalJournal of Cardiac Failure
Volume26
Issue number3
DOIs
StatePublished - Mar 2020

Keywords

  • Heart failure with preserved ejection fraction
  • biomarkers
  • chronic kidney disease
  • exercise capacity
  • sildenafil
  • trials

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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