Background:

Although acute chest syndrome (ACS) and pulmonary hypertension (PH) are each recognized as risk factors of sickle cell disease (SCD), the impact of a first-episode of ACS In patients with preexisting PH has not been well characterized. There is minimal literature exploring inpatient clinical outcome Including length of stay, in-hospital mortality, and the need for intensive care or intubation specifically in the subset if SCD patients who have existing PH at the time of their initial ACS.

Methods:

We conducted a retrospective cohort study using data from the United States Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) from 2016–2022. Adult patients hospitalized with a primary diagnosis of first episode of acute chest syndrome (ACS) and a documented history of pulmonary hypertension (PH) were identified using ICD-10 codes; repeat ACS admissions were excluded. The primary outcome was in-hospital mortality. Secondary outcomes included length of stay, hospital charges, and need for interventions such as mechanical ventilation, blood transfusion, or vasopressor support. Variables with p<0.2 in univariate analysis were included in multivariable regression models (logistic for mortality, linear for length of stay and charges), adjusting for age, sex, race, Charlson comorbidity index, hospital characteristics, and insurance status. Statistical significance was defined as p<0.05.

Results:

From 2016–2022, we identified an estimated 36,449 hospitalizations for acute chest syndrome (ACS), of which 4,999 (13.7%) occurred in patients with coexisting pulmonary hypertension (PH). The mean age of the PH group was 36.4 years, and 55.1% were female. The racial distribution was predominantly Black (95.1%), followed by Hispanic (3.5%) and White (0.2%).

Socioeconomic disparities were evident: 53.3% of PH patients resided in ZIP codes within the lowest income quartile (p = 0.0003), and 44.6% were insured by Medicaid (p < 0.0001). Most had at least one comorbidity, with 35.3% having a Charlson comorbidity index of 1. PH hospitalizations occurred primarily in large (66.9%), urban teaching hospitals (92.2%), and were most common in the Southern United States (44.7%) (all p < 0.001).

In adjusted analyses, PH was associated with significantly longer hospital stays (β = 1.54 days, 95% CI: 0.94–2.13, p < 0.001) and greater total hospital charges (β = $19,703, 95% CI: $10,705–$28,701, p < 0.001). PH was also independently associated with higher odds of intubation (OR = 1.71, 95% CI: 1.14–2.56, p = 0.01), but not with red blood cell transfusion (OR = 1.10, 95% CI: 0.02–59.47, p = 0.964). In-hospital mortality was not significantly different between groups after adjustment (OR = 0.94, 95% CI: 0.48–1.82, p = 0.851).

Independent predictors of in-hospital mortality included increasing age (OR = 1.04 per year, 95% CI: 1.02–1.06, p < 0.001), Charlson comorbidity index (OR = 4.74 for score = 2, p < 0.001; OR = 3.11 for score = 3, p = 0.005), and residence in the highest ZIP code income quartile (OR = 2.74, 95% CI: 1.03–4.84, p = 0.041). No significant associations with mortality were observed for sex, race, insurance type, hospital region, teaching status, or weekend admission.

Conclusion:

In this nationally representative cohort of patients hospitalized for acute chest syndrome (ACS), coexisting pulmonary hypertension (PH) was associated with longer hospital stays, greater healthcare costs, and higher intubation rates, reflecting increased clinical complexity. However, PH was not independently associated with in-hospital mortality. Instead, mortality was driven by age, comorbidity burden, and higher ZIP code income, suggesting potential disparities or late-stage recognition in less-expected populations.

These findings emphasize the substantial resource burden of PH in the setting of ACS among patients with sickle cell disease and highlight the need for earlier identification and standardized management of cardiopulmonary complications. Future prospective studies are needed to refine risk stratification and guide interventions that can improve outcomes in this vulnerable population.

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2025
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