Pulmonary hypertension as an independent predictor of mortality in hospitalized sickle cell disease patients: A national analysis of comorbidities and outcomes Free

Introduction: Sickle cell disease (SCD) is a prevalent inherited hemoglobinopathy characterized by chronic hemolytic anemia and recurrent vaso-occlusive phenomena, leading to progressive multi-organ dysfunction. Advances in disease-modifying therapies have extended survival, resulting in a growing adult SCD population increasingly affected by chronic cardiovascular complications. Among these, heart failure with preserved ejection fraction (HFpEF) and pulmonary hypertension (PH) have emerged as leading causes of morbidity and mortality.

Methods: Using the National Inpatient Sample (2016–2022), we identified 287,135 SCD hospitalizations. We examined the prevalence of HFpEF (3.7%) and PH (4.0%) and their associations with in-hospital mortality, length of stay and total charges. Patients were categorized into four groups: no HFpEF/no PH (93.3%), HFpEF only (2.7%), PH only (3.0%), and both HFpEF/PH (1.0%). Survey-weighted logistic regression assessed mortality odds, and linear regression evaluated LOS and charges, adjusting for demographics, comorbidities, and hospital characteristics.

Results: Among 287,135 SCD hospitalizations, unadjusted analyses showed HFpEF (OR 3.47, 95% CI 2.68–4.49, p<0.001) and PH (OR 3.61, 95% CI 2.83–4.60, p<0.001) strongly associated with increased mortality. Adjusted models confirmed PH (OR 1.71, 95% CI 1.30–2.25, p<0.001) but not HFpEF (OR 0.93, 95% CI 0.69–1.23, p=0.597) as an independent mortality predictor. Compared to SCD patients with HFpEF alone, patient with HFpEF and PH did not have increased mortality (OR 1.45, 95% CI 0.87–2.44, p=0.158). Similarly patient with both HFpEF and PH patients had no significant mortality increase compared to those with PH alone (OR 1.13, 95% CI 0.64–2.01, p=0.672). Crude mortality rates were 0.9% (no HFpEF/no PH), 3.3% (HFpEF only), 3.3% (PH only), and 4.0% (both). Over 2016–2022, HFpEF prevalence in SCD rose from 2.8% to 4.7% (OR 1.07, p<0.001) and the prevalence of PH rose from 0.1% to 5.7% (OR 1.28, p<0.001). LOS was higher in HFpEF and PH groups (6.83 days and 6.83 vs. 4.83, p<0.001) and charges were higher in these groups ($76,535 and $82,773 vs. $49,912, p<0.001). Overall patients with HFpEF had higher rates of chronic comorbidities such as diabetes (34.6% HFpEF, 18.4% PH, 24.96% both vs. 9.97% none), chronic kidney disease stage 3+ (48.4% HFpEF, 33.9% PH, 46.6% both vs. 8.49% none), and coronary artery disease (23.5% HFpEF, 14.1% PH vs. 4.72% none). Although SCD patient with PH had less chronic comorbidities than patients with HFpEF, both had higher rates of in-hospital complications including higher rates of mechanical ventilation (5.52% HFpEF, 5.56% PH, 5.10% both vs. 1.97% none) and ICU admission (6.09% HFpEF, 6.56% PH, 6.15% both vs. 2.18% none).

Conclusions: PH, but not HFpEF, independently predicts mortality in SCD patients. This is likely due to the higher rates of chronic comorbidities among HFpEF patients such as CKD and diabetes leading to higher overall mortality among these patients that is not directly attributable to HFpEF. Both conditions are associated with increased healthcare burden with statistically significant increase in length of stay and costs. Rising prevalence of HFpEF, PH, and their combinations in SCD underscores the need for targeted interventions to manage these complications. The identification of PH as an independent predictor of mortality in SCD can be used as an additional point to identify high risk patients but further research is needed to determine whether PH directly causes increased mortality or is a marker of SCD disease severity.