TY - JOUR
T1 - Renal Dysfunction in Heart Failure With Preserved Ejection Fraction
T2 - Insights From the RELAX Trial: Renal Dysfunction in RELAX
AU - Patel, RAVI B.
AU - MEHTA, RUPAL
AU - REDFIELD, MARGARET M.
AU - BORLAUG, BARRY A.
AU - HERNANDEZ, ADRIAN F.
AU - SHAH, SANJIV J.
AU - DUBIN, RUTH F.
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/3
Y1 - 2020/3
N2 - 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.
AB - 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.
KW - Heart failure with preserved ejection fraction
KW - biomarkers
KW - chronic kidney disease
KW - exercise capacity
KW - sildenafil
KW - trials
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U2 - 10.1016/j.cardfail.2020.01.003
DO - 10.1016/j.cardfail.2020.01.003
M3 - Article
C2 - 31931098
AN - SCOPUS:85079038813
SN - 1071-9164
VL - 26
SP - 233
EP - 242
JO - Journal of Cardiac Failure
JF - Journal of Cardiac Failure
IS - 3
ER -