Double jeopardy: Heart failure and thrombotic thrombocytopenic purpura in the inpatient setting

Abstract Background: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening microangiopathic disorder requiring urgent intervention, often with plasmapheresis. However, the presence of comorbid heart failure (HF)—a condition associated with hemodynamic instability and renal vulnerability—may alter the clinical trajectory of these patients. To date, the impact of HF on TTP-related inpatient outcomes has not been systematically evaluated in a nationally representative sample. Methods: Using the National Inpatient Sample (2016–2022), we identified adult hospitalizations with the diagnosis of TTP. Patients were stratified based on the presence or absence of comorbid HF. Rather than applying a traditional case-control framework, we treated this as a cohort study nested within real-world hospital data, incorporating discharge weights to produce national estimates. Outcomes were analyzed using multivariable logistic and linear regression models, adjusting for age, sex, race, hospital characteristics, and relevant clinical covariates. The primary outcome was in-hospital mortality. Secondary outcomes included inpatient complications, use of plasmapheresis, length of stay (LOS), and total hospital charges. Results: Among an estimated 8,481 hospitalizations with TTP, 1,605 (18.9%) involved patients with HF. The overall cohort was predominantly female (60.1%) and racially diverse, with 33.0% identifying as Black—underscoring the disease's known disproportionate impact on this population. HF was associated with a longer hospital stay (adjusted increase of 1.10 days; p = 0.043) and significantly higher total charges (β = +$33,312; p = 0.041). In-hospital mortality trended higher in the HF group (aOR 1.20, 95% CI: 0.995–1.44; p = 0.056), though not statistically significant. Clinically, HF was linked to markedly increased odds of several serious complications: cardiogenic shock (aOR 6.02, p < 0.001), respiratory failure (aOR 2.37, p < 0.001), dialysis (aOR 1.92, p < 0.001), acute kidney injury (aOR 1.53, p < 0.001), atrial fibrillation (aOR 2.50, p < 0.001), and ventricular tachycardia (aOR 2.95, p < 0.001). Notably, patients with HF had significantly reduced odds of receiving plasmapheresis (aOR 0.57, p < 0.001) and lower incidence of cerebral infarction (aOR 0.50, p < 0.001). Several other outcomes, such as transfusion requirement, encephalopathy, pulmonary embolism, and deep vein thrombosis, did not differ significantly by HF status.Conclusion: Approximately one in five TTP hospitalizations involve patients with pre-existing heart failure, a group that experiences more prolonged hospitalizations, increased resource utilization, and higher odds of severe complications, including cardiopulmonary and renal events. Despite these risks, HF patients were significantly less likely to receive plasmapheresis, raising questions about clinical decision-making and access to standard therapy. These findings highlight the heightened vulnerability of TTP patients with coexisting heart failure and the need for integrated cardiovascular and hematologic care to improve inpatient outcomes in this high-risk subgroup.