Background: ChronicCHF leads to volume overload and can cause bowel wall edema. This may compromise local immune defense and promote increased translocation of gut bacteria into the blood.HPBCs can cause biliary tract obstruction which is also associated with bacteremia. Additionally, cancer treatments are associated with an increased risk of clostridium difficile infection (CDI), regardless of antibiotic exposure. While associations between cancer and increased infection rates are well-established, we questioned whether concomitant CHF increases this risk further in the HPBC population. We therefore investigated whether concomitant CHF and HPBC influenced CDI, other infectious gastroenteritis (IGE), GNS rates or all-cause-hospital mortality. Methods: A retrospective study was conducted by obtaining patients with HPBC through the application of specific ICD 10 codes from the National Inpatient Sample 2020, a large publicly available database of inpatient hospital stays incorporating data from hospitals across 48 U.S. states. Among this cohort, patients with chronic CHF were further identified by applying all CHF-specific ICD 10 codes. All patients with HPBC were divided into two groups, one with CHF (group A) and the other without CHF (group B). Outcomes were compared between the two groups using multivariate regression analysis (MVRA) adjusting for demographic factors, hospital-specific characteristics like location, bed size, etc., comorbidities including obesity, diabetes, hypertension, prior cardiovascular events, HIV, CKD, OSA, etc., prior coronary intervention/surgery as well as alcohol, smoking or substance use. Results: 211,790 patients were identified with HPBC. 40.55% were female. 18,955 patients (9.95%) were found to have chronic CHF. The incidence of GNS was higher in group A compared to group B in the MVRA (Adjusted (Ad) OR: 1.4, CI 1.07-1.95, p=0.015). However, there was no difference in the incidence rate of CDI between groups A and B (Ad OR: 1.0, CI 0.71-1.50, p=0.86). Similarly, the two groups had no difference in other IGE (Ad OR: 1.0, CI 0.71-1.37, p=0.96). All-cause hospital mortality was slightly higher in group A than group B but failed to reach statistical significance (Ad OR: 1.1, CI: 0.99-1.29, p=0.069). Conclusions: GNS was more common in patients with HPBC who also had comorbid chronic CHF. Future investigations may focus on the effect of increased GNS on outcomes beyond hospitalization, correlation between the severity of CHF and GNS as well as primary site of HPBC and infection risk. Based on this signal-finding analysis, it is postulated that early inter-disciplinary collaboration between oncology and cardio-oncology/cardiology may have special significance in the management of patients with chronic CHF and HPBCs, the latter of which already carries a dismal prognosis.