Heterogeneity in association of myocardial injury and mortality in sepsis or acute respiratory distress syndrome by subphenotype: a retrospective study

Abstract

Rationale: Myocardial injury is common in acute respiratory distress syndrome (ARDS) and sepsis and associated with increased mortality. Two latent class analysis derived subphenotypes are associated with differential risk of mortality in these populations, though the association of troponin-I with mortality within each subphenotype is unknown.

Methods: The derivation (n = 597 in EARLI) and validation (n = 452 in VALID) cohorts consisted of patients with sepsis or ARDS admitted to the ICU and enrolled in two separate prospective observational studies. Patients with troponin-I measured between hospital presentation and within 24 h of ICU admission were included. A parsimonious classifier model using interleukin-8, soluble tumor necrosis factor receptor-1, and vasopressor use assigned patients to subphenotype. Association between peak troponin-I concentration and 60-day in-hospital mortality within each subphenotype was assessed through logistic regression adjusting for age, admission laboratory values, vasopressor use, invasive ventilation use, and cardiac comorbidities.

Results: Median peak troponin-I was significantly higher in the hyperinflammatory vs hypoinflammatory subphenotype in both cohorts (0.07 vs 0.04 ng/mL and 0.17 vs 0.07 ng/mL, both p < 0.05). The association between peak troponin-I and mortality differed between inflammatory subphenotypes (p-interaction 0.004, EARLI). In EARLI, each doubling of peak troponin-I was associated with increased adjusted odds of 60-day mortality (aOR 1.14, 95% CI 1.02-1.28) in the hypoinflammatory subphenotype only. These findings were corroborated in VALID (aOR 1.11, 95% CI 1.03-1.21 in hypoinflammatory).

Conclusions: Admission peak troponin-I is significantly associated with 60-day mortality in patients with sepsis or ARDS. This association was distinctly driven by the hypoinflammatory subphenotype.

Fig. 1

Median peak troponin-I higher in the hyperinflammatory compared to the hypoinflammatory (A). Higher proportion of elevated peak troponin-I above upper limit of normal for assay (ULN > 0.04ng/mL, red line, table insert) and a wider distribution of values in the hyperinflammatory phenotype (B)

Fig. 2

Median peak troponin-I by survival status at day 60. In the hypoinflammatory subphenotype, patients who died had higher peak troponin-I compared to those who survived (B); however, there were no differences in peak troponin-I by survival status within the hyperinflammatory subphenotype (C)

Fig. 3

Forest plot with crude and adjusted odds ratios for 60-day mortality associated with peak troponin-I concentrations, in EARLI. Adjusted for age, hypertension, diabetes, coronary artery disease, congestive heart failure, acute coronary syndrome, admission hematocrit, log-transformed white blood cell count, log-transformed creatinine, respiratory rate, heart rate, vasopressor on day 1, and invasive ventilation on day 1

Fig. 4

Differential probability of mortality according to probability of belonging to hypoinflammatory phenotype stratified by tertile of peak troponin-I concentration