The presence and prognostic effect of albuminuria in light of the rapid-up titration programme of guideline-directed medical therapy in heart failure

Introduction

Urine albumin-to-creatinine ratio (UACR) has an important prognostic role in heart failure (HF); however, its measurement is still not part of the routine care. Consequently, data are lacking on the prognostic effect of UACR in light of the rapid up-titration (RT) of modern guideline (GL)-directed medical therapy (GDMT), recommended by the 2023 ESC HF GLs for all patients after a HF hospitalisation (HFH).

Aims

To assess the changes of UACR in the effect of the 6-week RT programme (RTP), and to evaluate its prognostic (all-cause mortality [ACM], HFH) role in HF.

Patients and methods: A 6-week, universal RTP with regular follow-up controls was designed and implemented in the daily clinical practice of HF Outpatient Clinics of five national secondary/tertiary cardiology centres. UACR was measured in-hospital during the index HFH, thus before the RTP and after the 6-week RTP. The data of a consecutive group of 102 patients (male: 77%, age: 56 [49-64] years, de novo HF: 75%, LVEF: 24 [20-32]%, NT-proBNP at discharge: 1698 [837-3089] pg/mL, GDMT at discharge: RASi/target doses [TD] of RASi: 100%/17%, βB/TD βB: 97%/5%, MRA/TD MRA: 99%/73%, SGLT2i: 95%, triple therapy [TT: RASi + βB + MRA]/TD TT: 93%/0%, quadruple therapy [QT: TT + SGLT2i]/TD QT: 93%/0%) completing the RTP were assessed, who had UACR measured at both time points. Based on UACR values, patients were divided into three subgroups: A1: < 3 mg/mmol, A2: 3–30 mg/mmol, A3: > 30 mg/mmol.

Changes of UACR categories were compared using the McNemar test. The prognostic effect of UACR on HFH and the composite endpoint of ACM/HFH was analysed with Cox-regression analysis.

Results

At baseline, 60% of patients had A1 albuminuria, while 32% had A2 and 8% had A3. After the 6-week RTP, the ratio of patients on TDs of GDMT remarkably ameliorated (≥ 50% of TDs of QT: 75%, TD QT: 43%). After the GDMT optimisation, the proportion of patients with severe albuminuria decreased significantly (A1: 60% vs. 82%, A2: 32% vs. 15%, A3: 8% vs. 3%; before vs. after RTP).

After a median follow-up of 329 [229-465] days, HFH affected 4% of the total cohort, while ACM rate was 2%. The composite endpoint of ACM/HFH was observed in 6% of the patients. In the univariate Cox-regression analysis, de novo HF diagnosis, hyperkalaemia (serum potassium > 5 mmol/L) occurring during the 6-week RTP and baseline A3 albuminuria were predictors of HFH. Regarding the composite of ACM/HFH, de novo HF diagnosis and baseline A3 albuminuria were predictors in the univariate model.

Conclusions

Our multicentre observational study highlights that the UACR values significantly improved during the 6-week RTP in the effect of the GDMT optimisation. Moreover, based on our analysis UACR measurement may help to identify patients at higher risk for HFH, hence routine assessment of albuminuria may be part of daily clinical practice.Changes of UACR categoriesFor image description, please refer to the figure legend and surrounding text.