Longitudinal trajectories in clinical status and cardiac remodeling across the heart failure spectrum: 12-month evidence from the BRING-UP-3 HF Study
F Orso, C Basile, F Oliva, M G Cipriani, F Colivicchi, A Di Lenarda, M Gori, M Gorini, M Iacoviello, M Marini, D Gabrielli, A P MaggioniAbstract
Background
Heart failure (HF) remains a global health priority characterized by high morbidity and a complex clinical course. While randomized clinical trials have established the efficacy of disease-modifying therapies, real-world data describing the longitudinal evolution of symptoms, biomarkers, and echocardiographic parameters across the full spectrum of ejection fraction (EF) phenotypes remain limited.
Purpose
This study aimed to describe 12-month trajectories of clinical status, including New York Heart Association (NYHA) functional class, EF, and natriuretic peptide levels, across different EF phenotypes within a large nationwide implementation study.
Methods
The BRING-UP-3 HF study is a prospective, multicenter, observational study designed to improve the implementation of guideline-directed medical therapy (GDMT) in patients with HF involving 179 Italian cardiology centers. We analyzed 5,203 consecutive patients (median age 72 years, 76% male) included in the first enrollment phase. Data on clinical status, laboratory values, and echocardiography were collected at baseline, 6 months, and 12 months. EF categories were defined according to the Universal Definition of HF.
Results
The implementation of all recommended GDMT for specific HF phenotypes improved significantly over the12-month follow-up period (Figure 1). Significant dynamic improvements were observed across all phenotypes. The proportion of patients in NYHA class III-IV significantly decreased in all groups (p < 0.05). In patients with HF with reduced EF (HFrEF), median EF improved from 33% (interquartile range [IQR] 27%-37%) at baseline to 38% (IQR 30%-45%) at 12 months. Notably, 33% of patients with HF with mildly reduced EF (HFmrEF) transitioned to an EF ≥50%, whereas only 10.7% of patients with HF with preserved EF experienced an EF decline (Figure 2). Regarding biomarkers, median NT-proBNP levels declined by approximately 50% in HFrEF (from 1800 to 811 pg/mL) and HFmrEF (from 1337 to 700 pg/mL). Significant reverse left ventricular remodeling was evidenced by a reduction in functional valvular disease: the prevalence of moderate-to-severe mitral regurgitation (MR) decreased from 24.2% to 14.4% in HFrEF, and the prevalence of moderate-to-severe tricuspid regurgitation (TR) followed a similar downward trajectory (11.7% to 7.0%). Patients with HF with improved EF remained the most clinically stable, were already the least symptomatic at admission, and exhibited the lowest natriuretic peptide levels throughout the follow-up.
Conclusions
In a real-world setting, structured implementation of GDMT was associated with improved clinical status, favorable cardiac remodeling, and reductions in natriuretic peptide levels over 12 months of follow-up. These trajectories provide a benchmark for expected clinical recovery under contemporary GDMT.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.