Research Letter
April 8, 2024
Cardiac Function Before Sepsis and Clinical Outcomes
Stuthi Iyer, Jason N. Kennedy, Jacob C. Jentzer, et al
JAMA. Published online April 8, 2024. doi:10.1001/jama.2024.3917
Between 2009 and 2014, 21% of US adults with sepsis did not survive.1 Guidelines recommend urgent resuscitation of patients with sepsis, although the ideal treatment regimen is not clear2 and challenges to resuscitation, including the management of sepsis-related cardiac dysfunction, remain.3 How preexisting cardiac disease is associated with outcomes is poorly understood. This study characterizes heterogeneity in cardiac function prior to sepsis and describes associations with hospitalization outcomes and mortality.
Methods
Unique patients hospitalized from January 2013 to December 2014 at 12 community and academic hospitals affiliated with UPMC were included in this cohort study, with follow-up through December 31, 2019. We identified patients with sepsis using the Third International Consensus Definitions in the first 6 hours of presentation.4 Transthoracic echocardiography (TTE) findings were linked to patient data for up to 12 months prior to the sepsis episode. Clinical data were abstracted and included demographics and comorbidities before sepsis.
Preexisting cardiac abnormalities were categorized as none, right ventricular (RV), left ventricular (LV), or biventricular (BV) dysfunction based on the presence of either moderate or severe impairment of ventricular function on the TTE (<40%). Characteristics of patients with vs without TTE were compared to assess selection bias. Among patients who underwent TTE, acute illness severity, maximum values of biomarkers of organ dysfunction in the first 6 hours, provision of organ support, intensive care unit (ICU) admission, ICU and hospital length of stay, and mortality at 28 days, 365 days, and 3 and 5 years were compared by type of preexisting cardiac dysfunction. Descriptive data were compared using analysis of variance, the Kruskal-Wallis test, and the χ2 test with a Bonferroni-adjusted (2-sided) significance level of P < .05, as appropriate. Mortality was evaluated with Kaplan-Meier curves, log-rank tests, and multivariable logistic regression adjusted for age and sex. All analyses used Stata, version 18.0 (StataCorp LLC). The University of Pittsburgh institutional review board approved this minimal risk study with a waiver of informed consent.
Results
Of 513 281 patients, 31 052 met sepsis criteria, of whom 4599 (15.0%) had TTE data (mean [SD] age, 68 [5] years; 2277 [49.50%] male; 3871 [84.2%] White) (Table). Patients with TTE data were not meaningfully different in demographics or sepsis presentation compared with those without TTE data.
Of patients with TTE data, 974 (21.2%) had preexisting cardiac dysfunction. Of these, 136 (14.0%) had RV dysfunction, 715 (73.4%) had LV dysfunction, and 123 (12.6%) had BV dysfunction. The type of preexisting cardiac dysfunction was not associated with acute sepsis severity (Table). Presenting Sequential Organ Failure Assessment and systemic inflammatory response syndrome criteria were not significantly different. Vasopressor support was more common for patients with RV, LV, or BV dysfunction than no dysfunction (RV, 33.1%; LV, 36.1%; BV, 51.2%; none, 23.0%; P < .001), as was admission to the ICU (RV, 78.7%; LV, 75.2%; BV, 82.9%; none, 67.1%; P < .001). Neither ICU nor hospital length of stay significantly differed.
All-cause 28-day mortality was 9.6% for patients without TTE data and 19.2% for those with TTE data. Among those with TTE data, mortality was highest for patients with RV dysfunction (27.2%) and lowest for patients with no dysfunction (17.7%) (Figure). After controlling for age and sex, RV dysfunction (odds ratio [OR], 1.63; 95% CI, 1.10-2.41) and LV dysfunction (OR, 1.45; 95% CI, 1.19-1.76), but not BV dysfunction (OR, 1.50; 95% CI, 0.99-2.28), were associated with 28-day mortality (Table). Results were consistent at 365 days, 3 years, and 5 years, except for BV dysfunction, which became significant at 5 years.
Discussion
Despite similar clinical presentations and sepsis-related organ dysfunction, patients with preexisting cardiac dysfunction required greater organ support and admission to intensive care. Patients with LV or RV dysfunction had both higher short-term mortality and higher long-term mortality than patients with no cardiac dysfunction before sepsis.
Study limitations include that baseline TTE was not performed for all sepsis patients, leading to a potentially biased cohort due to selection. Results do not apply to cardiac dysfunction during the sepsis episode. Patients were enrolled a decade ago, but the interpretation of TTE data and sepsis care with early recognition and prompt antibiotics have not substantially changed. These data suggest that heterogeneity in cardiac function before sepsis may be associated with resuscitation and outcomes.
