Among patients with heart failure with preserved ejection fraction (HFpEF), visit-to-visit variability in laboratory indexes of kidney function and serum electrolytes is common and independently associated with worse long-term clinical outcomes, researchers reported in JAMA Cardiology.
In the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial, the investigators evaluated the association of visit-to-visit variability in kidney function (creatinine and blood urea nitrogen [BUN] levels) and serum electrolytes (sodium, chloride, and potassium) with the risk for adverse clinical outcomes among patients with chronic, stable HFpEF. The study authors assessed the adjusted associations during the first 4 months of follow-up and the risk for the primary outcome (a composite of aborted cardiac arrest, hospitalization for heart failure, or cardiovascular death) and all-cause mortality.
Investigators enrolled a total of 3445 patients (mean age, 68.5±10 years; 50.6% female) in the trial and analyzed 2479 (BUN) to 3195 (potassium) measurements. They found that higher visit-to-visit variability in BUN (hazard ratio [HR] per 1 SD higher average successive variability [ASV] 1.21; 95% CI, 1.1-1.33) and creatinine (HR per 1 SD higher ASV 1.13; 95% CI, 1.04-1.22) was independently associated with an increased risk for the primary composite outcome as well as mortality independent of other baseline confounders, changes in kidney function, changes in medication dosages, and variability in other cardiometabolic parameters, such as systolic blood pressure and body mass index.
The increased risk associated with greater variability in kidney function was consistent among the subgroups of patients who were stratified by the presence of chronic kidney disease (CKD) at baseline (CKD: HR per 1 SD higher ASV 1.39; 95% CI, 1.16-1.67; no CKD: HR per 1 SD higher ASV 1.13; 95% CI, 1.01-1.27) in the placebo and spironolactone treatment arms (placebo arm: HR per 1 SD higher ASV 1.27; 95% CI, 1.04-1.56; spironolactone arm: HR per 1 SD higher ASV 1.3; 95% CI, 1.03-1.65). Variability in sodium and potassium measures was significantly associated with a higher risk for primary composite events (sodium: HR per 1 SD higher ASV 1.14; 95% CI, 1.01-1.3 and potassium: HR per 1 SD higher ASV 1.21; 95% CI, 1.02-1.44).
“This cohort study of patients with chronic [HFpEF] suggests that higher visit-to-visit variability in creatinine, blood urea nitrogen, sodium, and potassium levels is significantly associated with a higher risk of adverse clinical outcomes independent of other potential confounders and changes in these parameters,” stated the study authors.
Among several study limitations, the investigators noted that the secondary analyses of the trial can be considered only exploratory and the results need confirmation in other cohorts of patients with stable HFpEF. Also, owing to the observational design of the study, the findings may be prone to selection bias.
“Our study findings have important clinical implications,” the researchers commented. “Variability in routinely monitored laboratory values can be performed to improve risk stratification of patients with heart failure.”
Disclosures: Some of the authors reported affiliations with pharmaceutical and medical technology companies. Please see the original reference for a full list of authors’ disclosures.
Segar MW, Patel RB, Patel KV, et al. Association of visit-to-visit variability in kidney function and serum electrolyte indexes with risk of adverse clinical outcomes among patients with heart failure with preserved ejection fraction. Published online November 18, 2020. JAMA Cardiol. doi: 10.1001/jamacardio.2020.5592