Cardio-renal-metabolic Syndrome: Clinical Features and Dapagliflozin Eligibility in a Real-world Heart Failure Cohort

Aims: The Cardiovascular Outcomes Retrospective Data analysIS in Heart Failure (CORDIS-HF) is a single-centre retrospective study aimed to (i) clinically characterize a real-world population with heart failure (HF) with reduced (HFrEF) and mildly reduced ejection fraction (HFmrEF), (ii) evaluate impact of renal-metabolic comorbidities on all-cause mortality and HF readmissions, and (iii) determine patients' eligibility for sodium-glucose cotransporter 2 inhibitors (SGLT2is).

Methods And Results: Using a natural language processing algorithm, clinical data of patients diagnosed with HFrEF or HFmrEF were retrospectively collected from 2014 to 2018. Mortality and HF readmission events were collected during subsequent 1 and 2 year follow-up periods. The predictive role of patients' baseline characteristics for outcomes of interest was assessed using univariate and multivariate Cox proportional hazard models. Kaplan-Meier analysis was used to determine if type 2 diabetes (T2D) and chronic kidney disease (CKD) impacted mortality and HF readmission rates. The European SGLT2i label criteria were used to assess patients' eligibility. The CORDIS-HF included 1333 HF patients with left ventricular ejection fraction (LVEF) < 50% (413 HFmrEF and 920 HFrEF), who were predominantly male (69%) with a mean [standard deviation (SD)] age of 74.7 (12.3) years. About one-half (57%) of patients presented CKD and 37% T2D. The use of guideline-directed medical therapy (GDMT) was high (76-90%). HFrEF patients presented lower age [mean (SD): 73.8 (12.4) vs. 76.7 (11.6) years, P < 0.05], higher incidence of coronary artery disease (67% vs. 59%, P < 0.05), lower systolic blood pressure [mean (SD): 123 (22.6) vs. 133 (24.0) mmHg, P < 0.05], higher N-terminal pro-hormone brain natriuretic peptide (2720 vs. 1920 pg/mL, P < 0.05), and lower estimated glomerular filtration rate [mean (SD): 51.4 (23.3) vs. 54.1 (22.3) mL/min/1.73 m , P < 0.05] than those with HFmrEF. No differences in T2D and CKD were detected. Despite optimal treatment, event rates for the composite endpoint of HF readmission and mortality were 13.7 and 8.4/100 patient years. The presence of T2D and CKD negatively impacted all-cause mortality [T2D: hazard ratio (HR) = 1.49, P < 0.01; CKD: HR = 2.05, P < 0.001] and hospital readmission events in all patients with HF. Eligibility for SGLT2is dapagliflozin and empagliflozin was 86.5% (n = 1153) and 97.9% (n = 1305) of the study population, respectively.

Conclusions: This study identified high residual risk for all-cause mortality and hospital readmission in real-world HF patients with LVEF < 50% despite GDMT. T2D and CKD aggravated the risk for these endpoints, indicating the intertwinement of HF with CKD and T2D. SGLT2i treatment that clinically benefits these different disease conditions can be an important driver to lower mortality and hospitalizations in this HF population.