Nizam, Muhammad Abdullah

Abstract Background: Chemotherapy-induced cardiomyopathy (CIC) is a serious, and often irreversible complication in patients treated for hematologic malignancies. While therapies for hematologic malignancies continue to evolve, data on trends in in-hospital mortality among patients with concurrent hematologic malignancies and CIC are limited, and disparities by race and sex remain poorly characterized. This study examines national trends and demographic disparities in in-hospital mortality among patients with hematologic malignancies who developed CIC. Methods: The United States (U.S) National Inpatient Sample (NIS) from 2016 to 2020 was queried for patients diagnosed with malignant hematologic and lymphoid neoplasms who also developed CIC. Hematologic malignancies were identified using ICD-10 codes C81–C96, which include: C81 for Hodgkin lymphoma; C82–C86 for non-Hodgkin lymphomas; C88 for malignant immunoproliferative diseases (e.g., Waldenström macroglobulinemia, heavy chain disease); C90–C95 for leukemias of lymphoid, myeloid, monocytic, mixed, and unspecified cell types; and C96 for other or unspecified malignant neoplasms of lymphoid, hematopoietic, and related tissue. CIC was identified using ICD-10 code I42.7. The study was exempt from institutional review board approval as the NIS database contains deidentified patient information. Multivariable regression analysis was performed to determine the odds of in-hospital mortality among patients with hematologic malignancies who developed CIC. Multivariable logistic regression followed by marginal effects was used to plot yearly trends in in-hospital mortality. All the outcomes were adjusted for gender, race, Charlson comorbidity index and hospital characteristics. P < 0.05 was used to determine statistical significance. The analysis was performed on STATA 16 software. Results: The study identified a total of 3,021,434 hospitalizations with hematologic malignancies, of which 11,115 (0.004%) had secondary diagnosis of CIC (mean age = 56.5 years, 52.5% males). Among 11,115 patients with hematologic malignancies who developed CIC, 740 (6.6%) patients died during the hospitalization. Multivariable logistic regression followed by marginal effects estimated a decrease in adjusted in-hospital mortality trend from 6.5% in 2016 to 4.3% in 2020. However, this decreasing mortality trend was not statistically significant after adjusting for gender, race, Charlson comorbidity index, and hospital characteristics (OR: 0.93; 95% CI: 0.83 – 1.05; trend p = 0.260). In-hospital mortality did not differ significantly between male vs. female patients with hematologic malignancies who developed CIC (OR: 1.02; 95% CI: 0.72 – 1.43; p = 0.921). There was no difference in overall in-hospital mortality of patients of White (reference) vs. Black (OR: 1.12; 95% CI: 0.72 – 1.76, p = 0.61) or Hispanic (OR: 0.63; 95% CI: 0.32 – 1.25, p = 0.18) race. However, males of the Black race demonstrated a lower in-hospital mortality vs. males of the White race (OR: 0.26; 95% CI: 0.09 – 0.77, p = 0.01). In addition, females of the Black race showed a higher in-hospital mortality vs. females of the White race (OR: 2.43; 95% CI: 1.40 – 4.25, p <0.01). Conclusions: In patients with hematologic malignancies who developed CIC, overall in-hospital mortality did not differ significantly by race alone. However, on sex-based stratification, Black males had lower in-hospital mortality compared to White males, while Black females had higher mortality than White females. These differences highlight potential race–sex disparities in outcomes that warrant further investigation.

Background: Despite obesity being a major cardiovascular risk factor, studies in heart failure populations have reported an inverse association between body mass index and mortality—a phenomenon termed the "obesity paradox." However, the consistency and shape of this relationship across different HF phenotypes and clinical subgroups remain unclear. This meta-analysis aimed to quantify the dose-response relationship between BMI and mortality in HF patients and assess potential variations across subgroups. Hypothesis: Higher BMI is associated with reduced mortality in patients with heart failure, and that this relationship varies across clinical subgroups and U-shaped relationship. Methods: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A search strategy was developed, and studies were extracted from Cochrane and PubMed databases through December 2023. The main outcomes were all-cause mortality, cardiovascular deaths, and heart failure hospitalizations. Data were summarized as hazard ratios with 95% confidence intervals, and a spline model was used to assess non-linear relationships, with 21.7 kg/m2 as the reference point in the dose-response curve. PROSPERO: CRD42023455124 Results: Thirty-three studies (457,124 person-years) showed that each 5 kg/m2 increase in BMI was significantly associated with a 6% reduction in all-cause mortality (HR 0.94; 95% CI 0.92–0.96). Significant reductions were observed in acute decompensated heart failure (7%), HFpEF (9%), HFrEF (8%), diabetes (9%), males (9%), and females (8%). Cardiovascular mortality declined by 5% per 5 kg/m2 increase. Non-linear analysis revealed a significant U-shaped relationship, with lowest all-cause mortality between BMI 21.7 and 39 kg/m2. Subgroup analysis showed significant non-linear all-cause mortality reductions in acute decompensated heart failure (23.5–26 kg/m2), HFpEF (21.7–31 kg/m2), HFrEF (21.7–43 kg/m2), females (24–25.5 kg/m2), diabetes (21.7–36 kg/m2), and non-diabetics (21.7–33 kg/m2). Conclusion: Higher BMI is significantly associated with lower all-cause and cardiovascular mortality in patients with heart failure, supporting the presence of an obesity paradox. This protective effect was consistent across clinical subgroups, including HFpEF, HFrEF, males, females, and individuals with diabetes. The BMI paradox was evident in patients with acute decompensated heart failure, HFpEF, HFrEF, females, and both with and without diabetes.