Background: Cardiovascular disease (CVD) and cancer share common risk factors, and cancer survivors experience elevated long-term cardiotoxicity. Traditional risk-based metrics require person-time denominators that are unavailable in aggregate public health databases. This study introduces a proportional co-listing framework to detect population-level cardiovascular surveillance signals on death certificates across cancer types and demographic strata. Methods: We conducted a national cross-sectional surveillance analysis using CDC WONDER Multiple Cause-of-Death data from 1999 to 2020 for decedents aged ≥ 15 years. Utilizing an “any-mention” framework, we calculated the Proportional Mortality Ratio (PMR), defined as the ratio of CVD co-listing on cancer-related death certificates to CVD listing on non-cancer certificates. Temporal trends were evaluated using joinpoint regression to estimate the average annual percent change (AAPC). Analyses were stratified by age, sex, race/ethnicity, geography, and index cancer subtypes (lung, colon, and leukaemia). Results: Of 56,014,102 death certificates analyzed, 13,917,133 (24.8%) listed a malignant neoplasm, of which 3,997,238 (28.7%) co-listed CVD. Across the lifespan, the overall PMR followed a reverse J-shaped curve. Proportional co-listing was highest in the youngest cohort (ages 15–24: PMR 1.828, 95% CI: 1.778–1.879), declined to a nadir at ages 55–64 (PMR 0.336, 95% CI: 0.335–0.337), and rose modestly in older adulthood. From 1999 to 2020, PMRs increased significantly across all adult age groups, peaking at ages 55–64 (AAPC 1.69%, 95% CI: 1.52–1.83, p < 0.001). Young-adult PMR elevations were consistently higher in male, metropolitan, and Hispanic/Latino decedents. Among subtypes, leukaemia demonstrated the highest relative CVD co-listing in young adults (PMR 2.174), whereas colon cancer showed no statistically significant elevation (PMR 1.173, 95% CI: 0.951–1.447). Conclusions: Cardiovascular co-listing on US cancer death certificates is highly patterned by age, demographics, and cancer subtype. While elevated PMRs in young adults are consistent with patterns previously reported in cardio-oncology literature, sub-unity PMRs in middle-aged and older adults may reflect under-documentation of cardiovascular comorbidities in oncology settings alongside denominator effects arising from frequent CVD listing on non-cancer certificates. Improving comorbidity documentation on death certificates may enhance the utility of national administrative data for cardio-oncology surveillance and research.

Introduction: Cardiovascular disease (CVD) is a leading cause of non-cancer death among cancer survivors, attributable to cardiotoxic therapies and cardiovascular risk factors. General population risk prediction tools, including ASCVD (Atherosclerotic cardiovascular disease), Framingham’s Score, and PREVENT (Predicting Risk of Cardiovascular Disease EVENTS), lack cancer-specific variables. We evaluated whether these models, even after statistical optimization, could predict cardiovascular mortality in cancer survivors. Methods: Using the National Health and Nutrition Examination Survey (NHANES) 2001–2018, linked with National Death Index (NDI) mortality data, we conducted a retrospective analysis of 634 and 429 cancer survivors, respectively, across model-specific cohorts free of baseline cardiovascular disease. Discrimination was assessed for ASCVD, Framingham Score, and PREVENT using standardized thresholds of 7.5% and 20%, as well as Youden-optimized cutoffs. Area under the curve (AUC) comparisons were performed using the DeLong non-parametric method. Results: Standard thresholds showed suboptimal discrimination across all models (AUCs: ASCVD 0.56, Framingham 0.53, PREVENT 0.64). In contrast, Youden-optimized AUCs (ASCVD: 0.68; PREVENT: 0.71; all p < 0.001, DeLong test). Optimization increased the “low-risk” group’s mortality rate from 2.8% to 4.1% (RR = 1.47), suggesting improved statistical fit came at the cost of overestimating the risk. Optimized thresholds outperformed conventional cutoffs, underscoring the necessity for recalibrated, cohort-specific risk stratification in cancer survivors. Conclusions: Standard risk scores have inadequate discrimination for cardiovascular mortality prediction in cancer survivors. Threshold recalibration improves statistical metrics but does not resolve the structural failure of these models to account for cardiotoxic exposure. Development of cardio-oncology-specific risk models incorporating oncologic exposures is therefore warranted.

Background: Cancer and heart failure (HF) are significant causes of morbidity and mortality worldwide. Moreover, there is increasing evidence of a relationship between HF and cancer. Although oncology has experienced significant advancements in cancer therapies, patients with a combination of these conditions represent an important clinical challenge due to varying outcomes among different demographic populations. Therefore, understanding these trends is crucial for targeted interventions. Aims: This study analyzed two decades of mortality data to examine the trends, patterns, and disparities in cancer-related and cancer with HF-related deaths across the United States (US). Methods: Mortality data from 1999 to 2020 were obtained using CDC WONDER, identifying cancer and cancer with HF-related deaths in adults age ≥25 years via ICD-10 codes. Demographic and regional distributions of mortality were analyzed utilizing statistical methods. Joinpoint regression analysis was used to determine trends in age-adjusted mortality rates (AAMR) and annual percentage changes (APC). Results: Between 1999 and 2020, there were 13,880,876 cancer-related deaths in the US, including 567,657 with HF listed as a cause of death. The AAMR for cancer-related deaths decreased from 343.7 to 252.4 per 100,000 (APC: −1.61% [95% CI: −1.70, −1.57] from 1999 to 2018, then −0.62% to 2020). Cancer with HF-related deaths initially declined (AAMR: 15.0 to 10.2 from 1999–2013) but increased from 2013 to 2020 (APC: +6.03%). Males had higher mortality rates than females for both conditions. Cancer-related mortality was highest among non-Hispanic (NH) Whites and Hispanics, while cancer with HF-related mortality was highest among NH Whites and NH American Indians/Alaska Natives. Geographically, the South had the most cancer-related deaths (37.3%), while the Midwest led in cancer with HF-related deaths (4.5%). Conclusions: Cancer-related mortality has declined overall, whereas mortality for cancer with co-existing heart failure has risen since 2013 after an initial decline. Disparities persist, with the highest burden in NH Whites, males, and those in rural or underserved areas. The findings underscore the need for focused interventions aimed at reducing mortality related to cancer and cancer with heart failure, particularly among the vulnerable population.

Background/Aim: The addition of an immune-checkpoint inhibitor (ICI) to chemotherapy improves outcomes in both early-stage and metastatic triple-negative breast cancer (TNBC). However, ICIs are associated with immune-related adverse events (irAEs), such as cardiotoxicity, raising concerns for patients receiving both anthracyclines and ICIs. We sought to determine if combining anthracycline and ICI in TNBC is associated with greater cardiotoxicity than anthracycline alone. Methods: A retrospective cohort study was conducted at a large academic center. Two cohorts were analyzed: anthracycline plus ICI and anthracycline alone. Demographics, comorbidities, medications, cardiac imaging, and outcomes were reviewed. Time to adverse cardiac events were compared. Results: A total of 382 patients were included: 297 received anthracyclines without ICI, and 85 received both. There were no major differences in baseline characteristics. The rate of acute cardiac events was 3.4% in the anthracycline-alone cohort and 3.5% in the anthracycline-plus-ICI cohort (p > 0.99) over a median of 1232 days of follow up (median of 1336 days in the anthracycline only group; median of 704 days in the ICI group). No significant differences in acute heart failure, acute coronary syndrome, myocarditis, or pericardial effusion were observed. Kaplan–Meier analysis showed no significant difference in cardiac event-free survival (p = 0.60). Furthermore, there was no significant difference in time to cardiac events between the two groups following competing risk analysis when accounting for both prior coronary artery disease (HR = 1.32, 95% CI: [0.42, 4.14], p = 0.64) and age (HR = 1.64, 95% CI: [0.52, 5.19], p = 0.40). Conclusions: This single-institution analysis did not identify a significant increase in cardiotoxicity with the addition of an ICI to anthracycline therapy in patients with TNBC. Active surveillance for cardiotoxicities should continue in patients receiving ICI in addition to anthracycline therapy.

Next-generation Bruton’s tyrosine kinase inhibitors (BTKis) such as acalabrutinib and zanubrutinib have improved treatment outcomes in B-cell malignancies, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström macroglobulinemia (WM), while reducing off-target toxicities compared to ibrutinib. However, their comparative cardiovascular safety profiles remain poorly characterized. This study evaluates real-world cardiovascular and clinical outcomes between zanubrutinib and acalabrutinib using a large multi-center database. We conducted a retrospective cohort study using the TriNetX Research Network (October 2017–December 2024) including adult patients with CLL, MCL, WM, or small B-cell lymphoma treated with zanubrutinib or acalabrutinib. Patients with prior exposure to other BTKis were excluded. After 1:1 propensity score matching, 2887 patients were included in each cohort. We assessed one-year outcomes including new-onset atrial fibrillation/flutter, cerebral infarction, hypertension, and all-cause mortality using Cox proportional hazards modeling. The rate of AF/flutter events observed in the zanubrutinib group (4.05%) was numerically lower compared to the acalabrutinib group (5.25%). Time-to-event analysis did not demonstrate a statistically significant difference in AF risk over time (HR 0.777, 95% CI 0.597–1.012; p = 0.06), which was similar in binary analysis (OR 0.761, 95% CI 0.581–0.997; p = 0.05). Cerebral infarction rates were similar between groups (1.09% vs. 1.12%), with no significant difference in time-to-event analysis (HR 0.984, 95% CI 0.596–1.626; p = 0.95) or binary analysis (p = 0.91). There was no significant difference in onset of hypertension in the zanubrutinib cohort (HR 1.199, 95% CI 0.957–1.501; p = 0.11) All-cause mortality was not statistically significant between the two groups (HR 0.865, 95% CI 0.740–1.012; p = 0.07). In this large, real-world analysis, fewer AF/flutter events were observed with zanubrutinib at one year; however, time-to-event analysis did not demonstrate a statistically significant difference in AF risk over time. Notably, hypertension, cerebral infarction, and all-cause mortality occurred at similar rates. This suggests zanubrutinib and acalabrutinib share similar cardiovascular safety profiles overall. However these findings are hypothesis-generating and require prospective validation before definitive conclusions about cardiovascular risk can be drawn.