Abstract Body (Do not enter title and authors here): Introduction: Takotsubo cardiomyopathy (TC) is a rare but clinically significant complication observed in patients undergoing chemotherapy. The relationship between TC and chemotherapy remains poorly understood. This study aimed to identify factors contributing to TC development and assess associated mortality risk.

Methods: We analyzed data from the National Inpatient Sample (NIS, 2016-2022) for adults admitted for chemotherapy. TC cases were identified using ICD-10 code "I51.81." Demographics and comorbidities were compared between TC and non-TC cohorts, with associations established through multivariable regression models. All-cause mortality rates were calculated. A non-parsimonious multivariate logistic regression model was employed, followed by a doubly robust method to estimate adjusted odds ratios for mortality in a matched cohort. Analyses were adjusted for the complex survey design of the NIS.

Results: Among 660,290 adults undergoing chemotherapy, 585 patients (89 per 100,000) developed TC. TC patients were older (mean age 60.4 vs. 54.3 years, p<0.01) and predominantly female, while non-TC patients were predominantly male. The TC cohort had higher prevalence rates of dyslipidemia, chronic kidney disease, frailty, valvular disease, and congestive heart failure (CHF)(Table 1). Female sex, frailty, and CHF were independent predictors of TC development(Table 2, Figure 1). Common complications in TC patients included acute kidney injury (29.06%), acute myocardial infarction (13.68%), mechanical ventilation requirement (15.38%), vasopressor use (6.84%), cardiogenic shock (5.98%), and ischemic stroke (4.27%). TC was associated with significantly higher all-cause mortality (12.82% vs. 1.44%; adjusted OR: 9.82, 95% CI: 4.34-22.55, p<0.01), prolonged hospital stay (16.85 vs. 7.26 days, p<0.01), and increased hospital charges ($335,897 vs. $108,704, p<0.01). Among TC patients, 29.06% required home health care services, while 45.30% had routine discharges.

Conclusion: TC is a rare complication in chemotherapy patients but carries substantial clinical significance, with nearly ten-fold increased mortality risk, prolonged hospitalizations, and tripled healthcare costs. Female sex, frailty, and heart failure serve as independent risk factors for TC development. These findings underscore the importance of enhanced monitoring protocols for high-risk patients during chemotherapy treatment.