e24005 Background: Systolic heart failure (SHF) and diastolic heart failure (DHF) can lead to volume overload and cause pulmonary venous congestion and pulmonary edema. While an association between lung cancer (LC) and increased infection rates is well established, we investigated whether chronic SHF or DHF, as well as acute SHF or DHF in concomitance with LC, influenced the incidence of pneumonia (PNA), sepsis, and septic shock. Methods: A retrospective study was conducted by obtaining patients with LC by applying specific ICD 10 codes (C34.0 - C34.9 including all sub-codes) from the National Inpatient Sample 2019-2020. Among this cohort, patients with acute and chronic SHF or DHF were further identified by applying specific ICD 10 codes ((I50.1 - I50.4 including all sub-codes). Pneumonia, sepsis, and septic shock outcomes were compared between LC patients with each of these types of heart failures versus those without using multivariate regression analysis (MVRA), adjusting for demographic factors, hospital-specific characteristics, common comorbidities and alcohol, smoking, or substance use. Results: 802,230 patients were identified with LC. 48.7% were female. 77.9% were Caucasian, 12.8% were African American, 4.6% were Hispanic, and 3.5% belonged to other ethnicities. Patients with LC and chronic SHF (n = 25880) had no significant difference in rates of PNA [Adjusted (Ad) odds ratio (OR): 0.9, p = 0.13] and sepsis (Ad OR: 0.9, p = 0.59) but had higher rates of septic shock (Ad OR: 1.4, p < 0.001) compared to those LC patients without any heart failure (HF). Patients with LC who had acute SHF (n = 22295) showed higher rates of PNA (Ad OR: 1.4, p < 0.001), sepsis (Ad OR: 1.5, p < 0.001), as well as septic shock (Ad OR: 1.6, p < 0.001) versus those without any HF. Patients with LC and concurrent chronic DHF (n = 31580) had similar rates of PNA (Ad OR: 1, p = 0.64), sepsis (Ad OR: 1.1, p = 0.62) and septic shock (Ad OR: 1, p = 0.77) compared to LC patients without any HF. However, acute DHF (n = 24080) led to a higher incidence of PNA (Ad OR: 1,4, p < 0.001) and sepsis (Ad OR: 1.2, p = 0.05) in patients with LC, but no difference in the incidence of septic shock (Ad OR: 0.8, p = 0.072). Conclusions: Chronic SHF led to an increased incidence of septic shock, whereas acute SHF was associated with accentuated rates of PNA, sepsis, and septic shock in patients with LC. Chronic DHF did not predict an increased risk of infections; however, acute DHF was associated with enhanced rates of PNA and sepsis. Future investigations may focus on the effect of SHF or DHF on outcomes beyond hospitalization in patients with LC and the subtypes of LC and infection risk. Based on this signal-finding analysis, it may be postulated that early inter-disciplinary collaboration between oncology and cardiology may be crucial in managing patients with heart failure and LC and potentially lead to better patient outcomes.