Phenotypic stratification and outcomes of new-onset heart failure in sepsis: a retrospective cohort study
A G Pradeep, Z Zubair, A Zayed, J Kaiyu, M B Moumneh, M Ennab, S El-Sayegh, M AmorAbstract
Background
Sepsis-induced cardiomyopathy is often viewed as a predominantly systolic phenomenon, yet emerging data suggest diastolic dysfunction may be equally prevalent. We investigated the clinical phenotypes, inflammatory profiles, and outcomes of new-onset heart failure (HF) during acute sepsis.
Purpose
This study aimed to characterize the clinical phenotypes and inflammatory signatures of new-onset HF in sepsis and determine whether distinct subtypes are associated with differential short-term outcomes.
Methods
A retrospective cohort study using electronic health records from a single-center healthcare system, identifying adult patients with sepsis between 2022 and 2025 via ICD-10 codes for sepsis, septic shock, and systemic inflammatory response syndrome (SIRS) of infectious origin. We included only patients whose first HF diagnosis coincided with their first sepsis encounter and excluded those with any prior HF history. Patients were classified into HF with preserved ejection fraction (HFpEF), HF with reduced ejection fraction (HFrEF), combined HFpEF/HFrEF, and unspecified HF groups using ICD-10 codes. Demographics, comorbidities, and peak inflammatory markers—C-reactive protein (CRP), lactate, procalcitonin, and white blood cell count (WBC)—were analyzed along with outcomes, including in-hospital mortality, length of stay (LOS), intensive care unit (ICU) admission, and all-cause readmissions. Appropriate parametric/non-parametric tests and chi-square analyses were used, with significance set at p < 0.05.
Results
Among 924 patients with incident HF during sepsis, final stratification yielded HFpEF (n = 438; 47.4%), HFrEF (n = 405; 43.8%), combined (n = 30; 3.2%), and unspecified (n = 51; 5.5%). HFpEF patients were older (mean 74.0 vs. 69.2 years; p < 0.0001) and more often female, whereas HFrEF patients were predominantly male (63.0%; p < 0.0001). Chronic obstructive pulmonary disease (COPD) exacerbation (21.5% vs. 13.1%; p = 0.004) and hypothyroidism (26.3% vs. 17.5%; p = 0.034) were more prevalent in the HFpEF group. Rates of acute kidney injury (AKI) did not differ between groups (p = 0.31). HFrEF patients exhibited higher markers of acute severity, including lactate (2.88 vs. 2.48 mmol/L; p = 0.009) and procalcitonin (8.52 vs. 7.24 ng/mL; p = 0.011). CRP trended higher in HFpEF (135.9 vs. 119.6 mg/L; p = 0.36). In-hospital mortality was similar between groups (HFpEF 28.1% vs. HFrEF 27.7%; p = 0.95), as were ICU admission rates (75.8% vs. 74.8%; p = 0.80) and LOS (449 vs. 459 hours; p = 0.74). HFpEF patients had a higher rate of readmissions (11.0% vs. 6.2%).
Conclusion
New-onset HF during sepsis occurs with both preserved and reduced ejection fraction, each with distinct clinical profiles. Despite differing severity markers, in-hospital outcomes were similar. HF with preserved ejection fraction was linked to higher readmission, indicating a need for targeted post-discharge management.