Cumulative cardiac risk strongly predicts in-hospital mortality and cost burden in patients hospitalized with chronic lymphocytic leukemia: A national inpatient analysis, 2020–2022

Abstract Background: Chronic lymphocytic leukemia (CLL) primarily affects older adults who often have preexisting cardiovascular comorbidities. Additionally, cardiotoxic therapies used in CLL, such as BTK inhibitors and anti-CD20 antibodies, may further increase cardiac risk. The national burden and cumulative impact of these complications on hospital outcomes remain underexplored. Methods: We analyzed the National Inpatient Sample database between 2020–2022 and identified adults hospitalized with primary or secondary diagnosis of CLL. Four cardiac complications were identified by ICD-10 codes: arrhythmia, heart failure, acute myocardial infarction (MI), and cardiac arrest. Multivariable survey-weighted logistic regression (for mortality), negative binomial regression (length of stay [LOS]), and log-link Gamma generalized linear models (cost) were performed for data analysis. We also constructed a Cardiac Risk Score (0–4) by summing the presence of these complications. Results: Among 48,955 (~240,000 weighted) CLL hospitalizations, cardiac complication prevalence was 35% for arrhythmia, 28% for heart failure, 5.5% for myocardial infarction (MI), and 1.3% for cardiac arrest. Overall, in-hospital mortality was 7.0%, with mean LOS of 6.5 days and mean charges of $86,422. After adjustment, arrhythmia and MI were independently associated with increased mortality (adjusted odds ratios [aOR] 1.22 and 1.88, respectively), while heart failure showed no significant association. Cardiac arrest, though rare, showed an expected high mortality risk. Cumulatively, each additional cardiac complication was associated with a 47% increase in mortality risk (aOR = 1.47; 95% CI: 1.41–1.53; p < 0.001). Although arrhythmia is less severe than MI or arrest, it was associated with a 9% longer hospital stay (IRR 1.09; 95% CI: 1.06–1.11) and 10% higher costs (cost ratio 1.10; 95% CI: 1.06–1.14), underscoring its significant clinical and economic burden. Conclusions: Cardiac complications are highly prevalent in hospitalized CLL patients and are associated with worsened clinical and economic outcomes. Beyond cardiac arrest, arrhythmia and MI significantly drive mortality and resource use. Importantly, a simple cumulative risk score revealed a dose-dependent increase in mortality, supporting the utility of early risk stratification and proactive cardiac management in this population.