Clinical Outcomes of Acute Chest Syndrome in Patients with Sickle Cell Disease and Pulmonary Hypertension
Authors: Lang Theodore , Lapping-Carr Gabrielle , Adegunsoye Ayodeji , Woelkers Megan , Wesevich Austin 
Published: December 2023

Introduction: Sickle-cell disease (SCD) is an inherited hemoglobinopathy frequently complicated by vaso-occlusive episodes (VOE) and acute chest syndrome (ACS). Likely due to chronic hemolysis and inflammation, roughly 10% of patients with SCD develop pulmonary hypertension (PH) (Gordeuk et al., 2016). Early signs of PH in patients with SCD often present as elevated pulmonary pressures and right ventricular (RV) dysfunction, which could be exacerbated by VOE or ACS (Dessap et al., 2007). Multiple studies have shown that ACS and PH are individually established causes of increased mortality in patients with SCD, but less is known about the relationship between concurrent ACS and PH and the effects on clinical outcomes. The diagnostic criteria for PH were recently updated, and the impact of those changes on outcomes in SCD remain unknown. We sought to evaluate clinical outcomes in patients with SCD who met PH diagnostic criteria when hospitalized for ACS.
Methods: We retrospectively collected clinical information from the electronic medical record (EMR) for all ACS admissions from 2017-2021 at the University of Chicago. Patients were assessed if they met PH diagnostic criteria based on available right heart catheterization (RHC) and transthoracic echocardiography (TTE) reports prior to the ACS admission date. PH was defined as having a mean pulmonary artery pressure &gt;20 mmHg on RHC, tricuspid regurgitation velocity (TRV) &gt;3.4 m/s, or TRV 2.9-3.4 m/s with two additional concerning TTE findings. ACS was defined as a new pulmonary opacity on imaging and at least one diagnostic symptom such as fever, chest pain, or hypoxemia. Depending on frequencies, chi-square or Fisher's exact tests were used to assess associations between PH and clinical outcomes: intensive care unit (ICU) transfer within 8 days of ACS diagnosis, 28-day readmission, and 28-day mortality. Two-sample t-test was used to assess the association between length of stay (LOS) and PH.
Results: There were 231 ACS admissions from 2017-21, but 1 admission was excluded from analysis due to lack of past medical history within the EMR. In total, 10 out of 230 ACS admissions (4%) met PH diagnostic criteria prior to admission, comprised of 8 out of 127 patients (6%). There were no significant associations between PH and clinical outcomes except for LOS (14.5 days for PH vs 9.1 days for no PH, p=0.04).
Conclusions: If a patient with SCD and PH was admitted for ACS, their LOS was 5 days longer than a patient without PH. An increased LOS may be due to a higher degree of complications such as elevated pain scores, prolonged oxygen requirements, or greater hemodynamic compromise. Future directions of the study will assess for causes of an increased LOS in the setting of PH. Only 6% of this cohort of patients with ACS admissions had PH, and this was likely under identified due to lack of adequate work-up (RHC or TTE). Diagnosis of PH prior to ACS admission may help with future prognostication and clinical decision-making regarding early intervention. The study highlights the increased healthcare requirements accompanying PH and a continued need to study PH, specifically in patients with SCD who may be at high risk for adverse clinical outcomes during an ACS episode.