Early respiratory–metabolic phenotypes predict 48-hour hemodynamic deterioration in intermediate-high risk pulmonary embolism

Background Early hemodynamic deterioration in intermediate-high risk pulmonary embolism (PE) is difficult to predict, as respiratory failure and systemic hypoperfusion may occur independently; integrating oxygenation, ventilatory demand, and metabolic markers may reveal high-risk phenotypes. Methods We prospectively classified 248 consecutive intermediate-high risk PE patients enrolled into the ongoing OPTRAPE registry, into four predefined respiratory–metabolic phenotypes (P) at admission. P1 was defined as ventilatory compensated (RR ≥24/min, P/F ≥250, lactate <2 mmol/L, no/low-flow oxygen; P2 as severe hypoxemic (P/F <250, RR ≥22/min, lactate <2 mmol/L, ≥low-flow oxygen), P3 as occult hypoperfusion (lactate ≥2 mmol/L, P/F ≥250, variable RR, no/low-flow oxygen) and P4 as combined respiratory–metabolic failure (P/F <250, lactate ≥2 mmol/L, RR ≥24/min, oxygen support required). The primary endpoint was 48-hour hemodynamic deterioration, and risk was analyzed using Cox and Fine–Gray models and net reclassification versus the simplified pulmonary embolism severity index (sPESI) Results During the 48-hour observation period, 30 patients (12.1%) experienced hemodyninamic deterioration, while 6 (2.4%) died suddenly without preceding hemodynamic compromise. The cohort was distributed across the four predefined P with relative balance: 31.5%, 25.8%, 21.8% and 21.0% for P1, P2, P3 and P4, respectively. The risk of 48-hr deterioration rose progressively across the phenotypes, from 2.6% in P1 to 7.8% in P2, 14.8% in P3, and 28.8% in P4 (p for trend <0.001). Median time to deterioration was 18 hours (IQR 9–30). The 48-hour event-free survival declined in parallel with phenotype severity: 97.4% in P1, 92.2% in P2, 85.2% in P3, and 71.2% in P4 (log-rank p<0.001) (Figure 1). Phenotype-based model had a C-index of 0.88 and an AUC 0.86, outperforming sPESI (AUC: 0.68; p<0.001) with a net reclassification improvement of +0.29, p=0.003. Competing-risk Fine–Gray analysis confirmed robustness (C-index of competing model 0.84) Conclusions Early respiratory and metabolic phenotyping identifies distinct risk trajectories in intermediate-high risk PE, supporting its use for early triage and management.