Relationship Between Cardiac Structure and Function With Renal Function Trajectory and Outcomes in Patients With Heart Failure: Insights From the PARAGON-HF Trial

Background: Renal dysfunction is common and associated with a poor prognosis in patients with heart failure. However, the association of cardiac structure and function with decline in kidney function in this population is unknown. We aimed to assess the association between individual measures of cardiac structure and function with changes in renal function and renal outcomes in patients with heart failure with preserved ejection fraction.

Methods: Patients enrolled in the PARAGON-HF (Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor With Angiotensin-Receptor Blockers Global Outcomes in Heart Failure With Preserved Ejection Fraction) echocardiographic substudy were included. The association between each echocardiographic parameter (expressed in standardized units) and changes over time in estimated glomerular filtration rate was calculated with repeated-measures mixed-effect models. Multivariable Cox proportional hazards models were used to identify individual cardiac parameters associated with the composite renal outcome (≥50% decline in estimated glomerular filtration rate relative to baseline, development of end-stage renal disease, or death attributable to renal causes), after adjusting for covariates.

Results: Among 1097 patients (mean age 74±8 years and 53% women), over a median follow-up of 2.9 years, 28 composite renal events (0.9 per 100 person-years) occurred. Higher left ventricular (LV) mass index and higher E/average e' ratio were associated with significantly more profound annual decline in estimated glomerular filtration rate (for both, -0.4 [95% CI, -0.7 to -0.1] mL/min/1.73 m²/y per 1 higher SD). Higher LV mass index, LV end-diastolic volume index, right ventricular end-diastolic area, and a lower right ventricular fractional area change were each associated with a significantly higher risk for the composite renal outcome.

Conclusions: In the PARAGON-HF echocardiographic substudy, higher LV mass and filling pressures were independently associated with more profound kidney function decline, and higher LV mass and volume, as well as impaired right ventricular structure and function, were each associated with renal events. Assessing these parameters may help identify patients with heart failure with preserved ejection fraction at higher risk for adverse renal events and indicate potential therapeutic targets.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920711.