Observational study for multiparametric assessment of cardiac congestion in outpatient worsening heart failure (EVOLUTION)

Aims We sought to characterize the clinical course of patients following worsening heart failure (WHF) treated in an outpatient setting and to identify factors associated with a poor response to standard of care with loop diuretics. Methods and results Between September 2022 and March 2023, 44 eligible patients (mean age 66.3 years, 84% male) with ejection fraction <50% and with WHF symptoms in the preceding week treated in an outpatient setting were enrolled. Patients were assessed weekly over 4 weeks following the WHF episode. At week 4, responses to fluid expansion and furosemide administration were assessed in 39 patients to unmask persistent subclinical congestion. Patients were on stable doses of guideline-directed medical therapy (GDMT) with a mean daily furosemide dose of 47.4 mg. Patient-reported and physician-assessed symptoms and quality of life improved over the 4 weeks. At 1 h following 1 L Ringer solution infused over 2 h, the median (interquartile range) urine volume and urine sodium excreted over 3 h were 300 (200.0-500.0) ml and 39.6 (12.4-63.0) mEq, respectively. Receiver-operating characteristic curves suggest that cystatin C >1.2 ng/ml, N-terminal pro-B-type natriuretic peptide (NT-proBNP) >1500 pg/ml, and high-sensitivity troponin T >20 pg/ml represent good predictors of non-response to a fluid challenge (diuresis, natriuresis, and rales) following an outpatient WHF, with having all three markers associated with the worst response. Conclusion Patients with high levels of troponin, or NT-proBNP, or cystatin C who develop WHF despite being treated with a loop diuretic, need novel therapies for WHF.