Angina of the kidney and the heart: the presence and prognostic impact of albuminuria in light of modern guideline-directed medical therapy in heart failure with reduced ejection fraction

Introduction Urine albumin-to-creatinine ratio (UACR) has an important role in a wide spectrum of cardio-renal syndrome, as it is essential in the diagnosis of chronic kidney disease (CKD) and is associated with a worse prognosis in heart failure (HF). However, measurement of UACR is not part of routine care in HF and data are lacking on the prognostic role of UACR in light of modern guideline-directed medical therapy (GDMT) in patients (pts) with HF with reduced ejection fraction (HFrEF). Aims To assess the role of UACR measurement on diagnosing CKD in a consecutive, hospitalised, HFrEF pt cohort and to analyse the effect of UACR on GDMT implementation and all-cause mortality (ACM). Patients and methods The data of 186 hospitalised, HFrEF pts between 01.09.2023 and 01.09.2024 were analysed retrospectively, who had UACR measured in-hospital (male: 75%, age: 60 [51–70] years, diabetes: 36%, coronary artery disease: 36%, atrial fibrillation: 45%, LVEF: 24 [20–30] %, NT-proBNP at admission: 5982 [2624–10567] pg/mL, eGFR at admission: 59 [47-75] mL/min/1.73m2; GDMT at discharge: RASi: 93%, βB: 90%, MRA: 94%, SGLT2i: 74%; triple therapy [TT:RASi+βB+MRA]: 86%, quadruple therapy [QT:TT+SGLT2i]: 69%). Based on UACR values, pts were divided into 3 groups: A1: < 3 mg/mmol, A2: 3–30 mg/mmol, A3: > 30 mg/mmol. CKD pts were defined as those with an eGFR value < 60 mL/min/1.73m² or with an eGFR value ≥ 60 mL/min/1.73m² and UACR ≥ 3 mg/mmol. GDMT at discharge was compared among UACR subgroups. ACM rates were investigated with Kaplan Meier method and log rank test. The predictors of ACM were tested with uni- and multivariate Cox regression model. Results The distribution of UACR categories were as follows: 53%, 38%, and 9% (A1, A2, A3, respectively). 51% of the pts had an eGFR < 60 mL/min/1.73m², and 16% had an eGFR ≥ 60 mL/min/1.73m² and concomitant A2/A3 albuminuria, thus altogether 67% of the pts had CKD. Pts with the most severe albuminuria were characterised by lower ratio of "de novo" HFrEF, higher comorbidity burden and NT-proBNP levels. Advanced albuminuria led to a lower application ratio of GDMT (RASi: 98% vs 94% vs 59%, βB: 95% vs 89% vs 71%, MRA: 100% vs 94% vs 59%, SGLT2i: 84% vs 68% vs 41%, TT: 95% vs 82% vs 53%, QT: 80% vs 61% vs 41%, p<0.05). ACM rates of pts with more severe albuminuria were higher (7%, 20%, 29%, p=0.026). Even though in the univariate Cox regression model UACR had a remarkable prognostic effect, in the multivariate analysis, older age, lower systolic blood pressure and the absence of the use of TT/QT, but not UACR was accompanied with worse prognosis. Conclusions Our results highlight the strategic role of the UACR measurement in the diagnosis of CKD and in the identification of higher risk HFrEF patients in everyday practice. Modern GDMT implementation was possible in a remarkable ratio of those higher risk HFrEF pts with severe albuminuria, which underscores the continuous effort to optimise GDMT among them as well.