Low-normal systolic blood pressure in heart failure: hemodynamic frailty in HFrEF, J-Curve phenotype in HFpEF/HFmrEF, and the prognostic role of in-hospital SBP drops—A targeted evidence synthesis
F Veneziano, F Magaro, M M Viscusi, F A GoiaAbstract
Background
The prognostic meaning of low-normal systolic blood pressure (SBP) in heart failure (HF) remains uncertain and may differ by left ventricular ejection fraction (LVEF). We synthesized contemporary registry and randomized trial evidence across HF phenotypes.
Methods
Structured synthesis of 11 major datasets (>80,000 patients) including OPTIMIZE-HF, Relax-AHF program trials, pooled HFpEF/HFmrEF trials (I-PRESERVE, TOPCAT, PARAGON-HF, DELIVER), and ambulatory HFrEF cohorts. Outcomes included 30-day, 180-day, and 1-year mortality and HF readmission.
Results
HFrEF — Discharge SBP and Outcomes In the Medicare-linked OPTIMIZE-HF registry, among patients with HFrEF (EF ≤40%) and stable SBP during hospitalization: Discharge SBP <130 mmHg vs ≥130 mmHg: 30-day mortality: 7% vs 4% HR 1.76 (95% CI 1.24–2.48; p=0.001) 1-year mortality: HR 1.32 (95% CI 1.15–1.53; p<0.001) After exclusion of patients with SBP <110 mmHg: Discharge SBP 110–129 mmHg vs ≥130 mmHg: 30-day mortality: HR 1.50 (95% CI 1.03–2.19; p=0.035) 1-year mortality: HR 1.19 (95% CI 1.02–1.39; p=0.029) These findings indicate increased risk even within the “low-normal” SBP range. Acute HF Trials — Continuous SBP and LVEF Interaction In a pooled individual patient-level analysis of four acute HF randomized trials (n≈10,500; baseline SBP 125–180 mmHg): SBP as a continuous variable: 180-day mortality: HR 0.93 per +10 mmHg (95% CI 0.89–0.98; p=0.008) Short-term composite outcome: HR 0.90 per +10 mmHg (95% CI 0.85–0.94; p<0.001) Significant interaction with LVEF: LVEF <40%: HR 0.84 per +10 mmHg (95% CI 0.77–0.92) LVEF ≥40%: HR 0.98 per +10 mmHg (95% CI 0.91–1.04) Thus, SBP was prognostic in HFrEF but not in preserved EF. HFpEF / HFmrEF — J-Curve Relationship In pooled data from four major HFpEF/HFmrEF outcome trials (n≈16,950): SBP demonstrated a J-shaped relationship with the primary endpoint. Lowest risk observed at SBP 120–130 mmHg. Highest SBP category vs 120–129 mmHg: HR 1.22 (95% CI 1.10–1.34) Pulse pressure (PP): J-shaped association. Highest PP quartile vs reference: HR 1.22 (95% CI 1.11–1.34) In hospitalized HFpEF patients (OPTIMIZE-HF): Discharge SBP <120 mmHg: 30-day mortality: 10% vs 5% HR 2.07 (95% CI 1.45–2.95; p<0.001) 1-year mortality: HR 1.36 (95% CI 1.16–1.59; p<0.001) SBP Drops During Hospitalization In pooled acute HF trials: SBP-drop occurred in 23% of patients. SBP-drop vs no SBP-drop: 180-day mortality: HR 1.21 (95% CI 1.05–1.39; p=0.009) Short-term composite outcome: HR 1.29 (95% CI 1.13–1.49; p<0.001) SBP <100 mmHg conferred the highest risk.
Conclusions
Low-normal SBP identifies a higher-risk phenotype in HFrEF, whereas HFpEF exhibits a J-shaped SBP-risk relationship with nadir at 120–130 mmHg. In-hospital SBP decline adds independent prognostic information. EF-specific and trajectory-informed interpretation of SBP may improve risk stratification.