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Abstract Repetitive head impacts are common in contact and collision sports and are linked to structural brain changes and an elevated risk of neurodegenerative diseases such as Chronic Traumatic Encephalopathy. Identifying early in vivo structural markers remains challenging. Although diagnosis currently requires post-mortem confirmation, clinical symptoms, including cognitive impairment and behavioural changes, are reflected in the diagnosis of Traumatic Encephalopathy Syndrome. These symptoms align with dysfunction in key brain regions—amygdala, hippocampus and thalamus—which support memory, emotion and behaviour and commonly show tau pathology in Chronic Traumatic Encephalopathy. This study uses shape analysis to examine structural differences in these regions between former American football players and unexposed asymptomatic controls and evaluates the influence of age, head impact exposure and clinical diagnosis on brain structure. We analyzed brain morphology in former American football players (n = 163) and unexposed, asymptomatic controls (n = 53). Structural segmentation was performed with FreeSurfer 7.1, and the shape analysis pipeline was used to generate subregional reconstructions. Vertex-level morphometry, based on the logarithm of the Jacobian determinant and radial distance, quantified local surface area dilation and thickness. Group differences were examined with covariate-adjusted linear regression models contrasting football players and controls, as well as participants with and without a Traumatic Encephalopathy Syndrome diagnosis. Partial correlations examined the influence of age, age of first football exposure and cumulative head impact index metrics, including frequency, linear acceleration and rotational force. Models were adjusted accordingly for age, body mass index, education, race, imaging site, apolipoprotein ϵ4 status and total intracranial volume. Former football players exhibited bilateral surface area contractions in the hippocampus and amygdala, along with reduced amygdala thickness, compared to controls. Older age was associated with widespread surface contractions and thinning across all regions, except for preserved thickness in the left hippocampus. An earlier age of first exposure to football correlated with surface contractions in the thalamus and left hippocampus. Greater cumulative linear acceleration was linked to bilateral hippocampal surface contractions and reduced thickness in the left thalamus, while greater rotational force exposure was associated with hippocampal thinning. No significant structural differences were found between players with and without a diagnosis of Traumatic Encephalopathy Syndrome. These findings extend volume-based research by revealing localized alterations in surface area dilation and thickness and emphasize the roles of age and repetitive head impact exposure in long-term brain changes.

Background: Lung cancer is classified into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC – including adenocarcinoma, squamous cell, and large cell carcinoma). The incidence of major adverse cardiovascular events (MACE)—defined as acute myocardial infarction, acute coronary syndrome/ischemic heart disease requiring revascularization, stroke, and cardiovascular death—have not been well defined in lung cancer patients following treatment. Coronary artery calcifications (CAC) and aortic calcifications (CA) are known cardiovascular risk markers in non-cancer populations. Purpose: To determine whether the presence of CAC or CA, as identified on baseline PET-CT (Positron Emission Tomography–Computed Tomography) or chest CT imaging, is predictive of MACE and all-cause mortality (ACM) in patients with lung cancer. Methods: We conducted a retrospective cohort study of patients diagnosed with SCLC or NSCLC who received chemotherapy, between January 1, 2010, and December 31, 2024. The baseline PET-CT or chest CT scans were reviewed for the presence of CAC and/or CA. Patients were excluded if they lacked baseline imaging or had experienced a MACE before treatment. Univariate and multivariate adjusted Cox regression models were employed to assess associations between CAC/CA and MACE or ACM. The Kaplan-Meier survival analyses was performed to evaluate event-free survival. Results: A total of 385 patients were included (mean age: 74 years, IQR: 67–79), predominantly female (158 [55%]) and white (279 [96.2%]). NSCLC was found in 255 (88%) and SCLC in 35 (12%). CAC was identified in 172 (60%) and CA in 87 (30%). Among patients with NSCLC, the presence of CAC was significantly associated with MACE (HR: 2.84 [95% CI: 1.6–4.8], p=0.0001) (Fig. a), particularly in those with adenocarcinoma (Fig. b). In SCLC, (HR: 1.56 [95% CI: 0.1–14.0], p=ns). On multivariable analysis, CAC remained the strongest predictor of MACE after adjusting for age, hypertension, diabetes, dyslipidemia, and smoking status (HR: 2.6 [95% CI: 1.5–4.4], p=0.0008) (Fig. d). No significant association was found between CA and MACE in either group (p>0.05). ACM was similar for SCLC, squamous cell, and NSCLC (Fig. c). Conclusion: In patients with NSCLC especially lung adenocarcinoma, the presence of CAC in the baseline PET/CT was an independent predictor of MACE. This finding supports the value of CAC as a non-invasive cardiovascular risk marker.

Introduction: Anthracycline-induced left ventricular dysfunction is well documented in lymphoma patients. However, the impact of cardiovascular risk factors (CVRF) and obesity on the right ventricle (RV) remains poorly characterized. Hypothesis: How does baseline CVRF burden—including obesity—affect RV structure and function over time in lymphoma patients treated with doxorubicin-based chemotherapy? Methods: A prospective cohort of patients with Hodgkin or non-Hodgkin lymphoma treated with doxorubicin-based chemotherapy at Mayo Clinic between March 1, 2013, and December 31, 2024, underwent echocardiography prior to chemotherapy initiation (T0), at 3–6 months (T1) and 6-18 months (T2) after treatment completion. A dedicated RV 4-Chamber view was used for all measurements. Patients were stratified into five groups: BMI>30, BMI>35, no CVRF, 1 CVRF (hypertension, diabetes, dyslipidemia, or smoking status), and ≥2 CVRF. RV parameters included end-diastolic/systolic area, FAC, TAPSE, S′ velocity, TRV, RVSP, and RV free wall strain. Group and time differences were analyzed using the Kruskal–Walli’s test due to non-normal distribution. Results: Among of 356 lymphoma patients (mean age 59.2 years, IQR:46-69) predominantly male (63.7%), 39.3% met criteria for obesity. At T0, patients with BMI >35 had greater RV end-diastolic (20.4 ± 4.4 vs. 18.7 ± 3.5 mm; p=0.009) and end-systolic diameters (11.0 ± 2.1 vs. 9.9 ± 2.6 mm; p=0.024), higher TRV (2.5 ± 0.4 vs. 2.2 ± 0.3 m/s; p<0.001) vs. no CVRFs. TAPSE was reduced vs. >2 CVRF group (23.7 ± 4.2 vs. 22.1 ± 4.8 mm; p=0.032). At T1, BMI >35 patients showed increased RV end-diastolic (22.3 ± 3.6 mm; p<0.001) and end-systolic areas (12.8 ± 2.9 mm; p<0.001), and worsened RVFWS (−24.0 ± 4.7% vs. −26.1 ± 2.98%; p=0.001) vs. no CVRF. RVSP was higher in those with >2 CVRFs (32.3 ± 5.4 mmHg; p=0.001). At T2, RVFWS was reduced in obese patients (−22.9 ± 3.5% vs. −27.1 ± 4.0%; p<0.001). RVSP stayed elevated in BMI >35 (33.0 mmHg) and >2 CVRFs (30.7 mmHg) vs. no CVRFs (23.7 mmHg; p<0.001). FAC and S′ did not differ significantly. Conclusion: In lymphoma patients treated with anthracyclines, isolated obesity was associated with the most pronounced RV changes—greater than those seen in non-obese patients with other CVRFs. These early and persistent alterations underscore the need for dedicated cardio-oncology care regardless of additional risk factors.

Background: Left atrial (LA) strain, measured by two-dimensional speckle tracking (2D-STE), has not been explored in lymphoma patients before anthracycline treatment as a prognostic marker for predicting future major adverse cardiovascular effects (MACE), heart failure, cardiotoxicity, and all-cause mortality after treatment. Hypothesis: Can an abnormal baseline LA peak reservoir strain (LA RS) measured before anthracycline chemotherapy predict MACE, heart failure, cardiotoxicity, and all-cause mortality in lymphoma patients? Methods: A retrospective cohort study was conducted including 104 patients diagnosed with Hodgkin and non-Hodgkin lymphoma, enrolled and followed from January 1, 2013, to June 30, 2023. LA RS was measured in a dedicated 4 chamber view (TomTec Imaging Systems, Unterschleissheim, Germany), abnormal values defined as less than 35%. Univariate Cox regression analyses were performed to assess whether the LA RS was associated with the development of MACE, cardiotoxicity, heart failure, and all-cause mortality. Multivariable Cox regression models were used to adjust for comorbidities. Associations with outcomes were evaluated using the Kaplan-Meier method and Cox regression. Results: Among 104 patients (mean age of 59 years; [IQR], 49–70), 69 (66.3%) were male and 102 (98.1%) were white. MACE occurred in 19 patients, heart failure in 14 patients, and cardiotoxicity was observed in 4 patients. Additionally, all-cause mortality was found in 19 patients (18.3%). Abnormal LA RS was significantly associated with increased all-cause mortality (HR 3.12, 95% CI 1.02–9.53, p=0.0454) (Figure c), even after adjusting for hypertension, dyslipidemia, smoking status, gender and age (Figure d). No significant associations were found between LA RS and MACE (HR 1.42, 95% CI 0.56-3.62, p=0.4604) (Figure a), heart failure (HR 1.12, 95% CI 0.38-3.24, p=0.8299), or cardiotoxicity (HR 3.23, 95% CI 0.33-31.47, p=0.3128) (Figure b). Conclusions: Abnormal baseline LA strain measured by echocardiography is an independent predictor of all-cause mortality in lymphoma patients. These findings support the use of LA strain assessment into initial risk stratification protocols, providing particular value in identifying patients at increased risk of mortality.

Background: Sepsis survivors experience substantial long-term cardiovascular (CV) morbidity and mortality. The pooled-cohort atherosclerotic cardiovascular disease (ASCVD) score estimates 10-year risk in the general population, but its accuracy soon after sepsis is unknown. Objectives: (1) Describe the absolute five-year incidence of major adverse cardiovascular events (MACE) after sepsis hospitalization. (2) Evaluate the discrimination and calibration of the 10-year ASCVD score for predicting five-year MACE in this setting. Research Questions: The ASCVD score would underpredict five-year MACE in sepsis survivors, reflecting their heightened risk. Methods: We performed a retrospective closed-cohort study using electronic health records from Mayo Clinic hospitals (USA). Adults aged 40–75 years hospitalized for sepsis between 2018 and 2020 were eligible if follow-up was ≥5 years; the age criterion matched the derivation range of the ASCVD score. The primary outcome was five-year MACE—myocardial infarction (MI), ischemic or hemorrhagic stroke, or CV death. Secondly we evaluated the predictive performance of ASCVD score for five-year MACE. Discrimination was assessed with the area under the receiver-operating curve (AUROC); calibration with Calibration-in-the-Large (CITL, ideal = 0) and slope (ideal = 1). Performance metrics were calculated in patients with complete ASCVD variables. Results: A total of 6306 sepsis admissions were screened. 2424 patients were excluded for age outside 40–75 years and 879 for <5 year follow-up, leaving 2718 patients for incidence analyses. Median age was 65 years (IQR 56–70); 55 % were male, 38 % required ICU care, and 91 % were White. Median body-mass index was 28.2 kg/m2 (IQR 23.7-34.7). During follow-up, 125 patients (4.6 %) had MI, 219 (8.1 %) experienced stroke, and 303 (11.1 %) died of CV causes; overall, 1573 patients (57.9 %) met the composite MACE outcome. Complete ASCVD data were available for 409 patients. In this subset, discrimination was moderate (AUROC 0.65; 95 % CI 0.59–0.71). Calibration showed CITL +0.34 (95 % CI 0.09–0.59) and slope 0.50 (95 % CI 0.28–0.72), indicating systematic infra-prediction and over-fitting, respectively. Conclusion: Five-year MACE incidence after sepsis is high. The 10-year ASCVD score moderately discriminates but underestimates five-year CV risk in this population, highlighting the need for sepsis-specific predictive models or recalibration to guide targeted post-sepsis cardiovascular prevention.

Background: The comparable long-term benefits of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with multivessel disease remains limited in underrepresented populations, particularly in patients with multivessel coronary artery disease and heart failure with severely reduced left ventricular ejection fraction (LVEF <35%). Research Question: Among patients with HF and LVEF < 35% which revascularization strategy (CABG or PCI) provides superior long-term clinical outcomes? Methods: We conducted a systematic review and meta-analysis of observational studies involving patients with ischemic heart disease (IHD), HF and LVEF < 35% undergoing PCI or CABG with a minimum follow-up duration of five years. PubMed, Embase, and Cochrane databases were searched for studies published up to April 15, 2025. We computed hazard ratios (HR) from propensity score matched results. We used Cochrane Review Manager version 9.2.1 for statistical analysis. The primary endpoints of interest included all-cause mortality at 5 to 10 years, repeat revascularization, and all-cause mortality at 10 or more years. Results: We included 8 studies with 12,697 patients (6,187 PCI vs 6,510 CABG). Median follow-up duration ranged from 3.8 to 5.2 years, with the longest reported follow-up up to 13 years. The cumulative, propensity adjusted, incidence of all-cause mortality was significantly lower in the CABG group compared to PCI in 5 to 10 years of follow-up (HR 0.61; 95% CI 0.54-0.69; p<0.001) and ≥ 10 years (HR 0.63; 95% CI 0.53-0.74; p<0.001). Additionally, CABG was associated with a reduced need for repeat revascularization in the 5 to 10 year time frame, with a HR of 0.42 (95% CI 0.22-0.81; p=0.01). Conclusion: In this systematic review and meta-analysis of patients with IHD and an ejection fraction ≤ 35% undergoing revascularization, CABG was associated with a reduction in all-cause mortality at ≥ 5 and ≥ 10 years of follow-up, as compared to PCI.

Importance The prevalence of cardiovascular disease differs substantially across neighborhoods. However, few studies have examined the contribution of neighborhood-level structural racism to inequities in cardiovascular health. Objective To investigate the association between neighborhood-level manifestations of structural racism and the prevalence of cardiovascular clinical and behavioral risk factors and cardiovascular diseases. Design, Setting, and Participants This cross-sectional study consisted of 71 915 US census tracts. The Structural Racism Effect Index (SREI) was appended to the 2020 Centers for Disease Control and Prevention’s PLACES dataset. Race and ethnicity were self-reported and obtained from the 2019 American Community Survey 5-year estimates. Data analysis was conducted from June 2024 to October 2024. Exposure The SREI is a composite score of census tract measures within 9 domains affected by structural racism (built environment, criminal justice, education, employment, housing, income and poverty, social cohesion, transportation, and wealth). The SREI scores were categorized into distribution-based quintiles, where higher quintiles represented greater neighborhood structural racism. Main Outcomes and Measures Neighborhood-level prevalence of cardiovascular clinical (high blood pressure, high cholesterol, obesity, and diabetes) and behavioral (current cigarette smoking and no leisure-time physical activity) risk factors and cardiovascular disease (coronary heart disease and stroke). Multilevel-linear mixed models, adjusting for confounders, were used to estimate adjusted prevalence rate ratios (aPRR). Results Among 71 915 census tracts, neighborhoods in the highest quintiles of structural racism were more likely than neighborhoods in the lowest quintile to be in the southern region (quintile 1, 19.9% vs quintile 5, 56.8%). The proportion of the population that was Black was largest in neighborhoods in the highest quintile of structural racism (quintile 1, 2.2% vs quintile 5, 23.0%). After adjustment, compared with the lowest quintile of structural racism, the highest quintile had significantly higher prevalence rates of cardiovascular clinical risk factors, including high blood pressure (aPRR, 1.37; 95% CI, 1.37-1.38), obesity (aPRR, 1.40; 95% CI, 1.39-1.40), and diabetes (aPRR, 1.80; 95% CI, 1.79-1.81). Similarly, for cardiovascular behavioral risk factors, the highest quintile of structural racism had significantly higher prevalence rates of current cigarette smoking (aPRR, 1.84; 95% CI, 1.83-1.85) and no leisure-time physical activity (aPRR, 1.88; 95% CI, 1.87-1.89). Additionally, for cardiovascular diseases, the highest quintile of structural racism had higher prevalence rates of coronary heart disease (aPRR, 1.80; 95% CI, 1.79-1.82) and stroke (aPRR, 1.99; 95% CI, 1.98-2.00). Conclusions and Relevance In this cross-sectional study, structural racism was associated with inequities in neighborhood cardiovascular health, highlighting opportunities for place-based prevention efforts.

ABSTRACT Background The efficacy and safety of PolarX cryoballoon for pulmonary vein isolation (PVI) among patients with atrial fibrillation (AF) is unclear. Methods PubMed, Embase, Cochrane Central, and ClinicalTrials.gov were systematically searched for studies comparing the PolarX vs. standard cryoballoon (CB‐2/CB‐4). Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (95% CIs) were computed for binary and continuous outcomes, respectively. Results This systematic review and meta‐analysis included 2 randomized controlled trials and 18 observational studies with a total of 7107 patients, of whom 3.188 (44.8%) underwent ablation with PolarX. When compared to standard cryoablation, PolarX had similar incidence of atrial arrhythmias recurrence (OR 1.04; 95% CI 0.82–1.32; p = 0.73), acute PVI success (OR 0.91; 95% CI 0.31–2.68; p = 0.98), and procedural duration (MD 3.41; 95% CI ‐2.89 to 9.71; p = 0.29). However, PolarX was associated with higher persistent phrenic nerve palsy (OR 2.17; 95% CI 1.26–3.74; p = 0.005) and a lower nadir temperature in all veins. Additionally, in a subgroup analysis of randomized trials and propensity score matching studies, similar findings were noted for recurrence of atrial arrhythmias. Conclusion In patients with AF undergoing PVI, PolarX had similar acute PVI success, procedural duration, and recurrence of atrial arrhythmias as compared with standard cryoballoon technology, however, was associated with a lower nadir temperature, and higher rates of persistent nerve palsy.