Citations

Abstract Background Marfan syndrome (MFS) predisposes individuals to aortic dissections. Recent data suggest that atrial fibrillation and atrial flutter (AF/AFL) may increase complications and mortality in MFS patients; however, their independent role in aortic dissection remains unclear. Purpose This study aims to assess the risk of aortic dissection in MFS patients with and without AF/AFL. Methods Using the TriNetX database and ICD-10 codes, 2,447 MFS patients with AF/AFL and 20,520 without were identified. Demographics (age, sex, race, ethnicity) were evaluated, and aortic dissection outcomes were compared using risk ratios and Kaplan-Meier survival analysis. Results Patients in the AF/AFL cohort were older (mean age 60.9 ± 16.7 years vs. 38 ± 16.6 years) and had higher proportions of males (62.51% vs. 56.76%) and white patients (74.67% vs. 66.3%). Aortic dissections occurred in 13.9% of MFS patients with AF/AFL compared to 3.4% of those without, resulting in a risk difference of 10.5% (95% CI: 9.0%–11.9%) and a risk ratio of 4.04 (95% CI: 3.547–4.603). Kaplan-Meier analysis revealed significantly lower survival rates in the AF/AFL cohort (74.07% vs. 90.63%; log-rank test, p < 0.0001), with a hazard ratio of 4.232 (95% CI: 3.686–4.858). Conclusion In MFS patients, those with AF/AFL were over four times more likely to experience aortic dissection and had over four times the hazard of mortality. Screening and managing AF/AFL may be essential to preventing aortic dissections and improving outcomes in this population.Figure 1

Abstract Background Vascular Ehlers-Danlos syndrome (VEDS) and Marfan’s syndrome are associated with cardiovascular complications, including arrhythmias. However, ventricular tachycardia (VT) risk in these populations has not been frequently reported. Purpose This study aims to assess the VT risk in VEDS and Marfan's syndrome patients through an international database. Methods The TriNetX database was used to pull patients with a diagnosis of VEDS and Marfan's Syndrome. Baseline characteristics (e.g., demographics, cardiovascular comorbidities, etc.) were collected, and propensity score matching was performed to balance the cohorts. Risk analysis and Kaplan-Meier survival were used to assess outcomes. Results A total of 1,114 and 23,172 patients had VEDS and Marfan’s syndrome, respectively. After propensity score matching, each cohort included 1,091 balanced patients regarding demographics and clinical characteristics. The cohorts were balanced with a mean age of 37.7 ± 16.0 years in both groups. 68.7% and 68.8% were females in the VEDS and Marfan cohorts, the majority being White (82.2% in VEDS, 82.9% in Marfan’s). VT Incidence was lower in VEDS (0.9%) compared to Marfan’s syndrome (2.6%), with a risk difference of -0.016 (p = 0.003). Kaplan-Meier survival showed higher survival in VEDS (99.44%) vs. Marfan’s (94.04%, log-rank p = 0.002). The risk ratio for VT in VEDS was 0.357 (95% CI: 0.174, 0.732). Conclusion VEDS patients have a significantly lower VT risk compared to those with Marfan’s syndrome. These findings suggest significant differences in the arrhythmic burden between these connective tissue disorders, which can direct future risk stratification and management strategies.

Background Immune‐checkpoint inhibitors (ICI) are associated with adverse cardiac events. Although troponin elevation is a diagnostic criterion for ICI‐related myocarditis (ICIrM) and myocardial infarction, data on other causes of troponin elevation and their outcomes in ICI‐treated patients are limited. Methods All patients treated with ICI who had hs‐TnT (high‐sensitivity troponin T) measured at a multicenter institution from 2011 to 2022 were included. Clinical data, outcomes (cardiac death, heart failure (HF), major adverse cardiovascular events [myocardial infarction, stroke, heart failure]), and cause of hs‐TnT elevation were assessed. Risks of cardiac events were compared across hs‐TnT elevation causes. Results Of 5423 patients treated with ICI, 1669 had post‐ICI hs‐TnT measurement (mean age 68.7±11.3 years, 58.3% male), with 1‐year follow‐up. Hs‐TnT elevation in patients with ICIrM (n=59) was associated with the highest risk for cardiac death (hazard ratio [HR], 52.7 [95% CI, 11.7–238.0], P <0.001), followed by hs‐TnT elevation due to heart failure (HR, 15.9), myocardial infarction/type 2 ischemia (HR, 11.6), and infection/sepsis (HR, 5.7), compared with those with no hs‐TnT elevation. ICIrM also carried highest risk for major adverse cardiovascular events (HR, 8.2, [95% CI, 4.4–15.3], P <0.001), followed by myocardial infarction/type 2 ischemia (HR, 8.1), heart failure (HR, 7.6), pulmonary embolus (HR, 5.1), infection/sepsis (HR, 4.1), and indeterminate cause (HR, 2.4). Among ICIrM, HsTnT value >576 ng/L best predicted risk for cardiac death and >319 ng/L for major adverse cardiovascular events. Conclusions Hs‐TnT elevation after ICI therapy is associated with increased risk of cardiac events, particularly in ICIrM, and a graded prognostic association depending on the cause of hs‐TnT elevation. Identifying the underlying cause and troponin thresholds may guide risk stratification and management.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased morbidity, mortality, and healthcare expenses. Meanwhile, effective management of AF requires a comprehensive, patient-centered approach that includes risk factor modification, rate and rhythm control strategies, and prevention of thromboembolic events. Multidisciplinary AF clinics have emerged as a model for comprehensive management to improve patient outcomes and reduce healthcare burden. This review discusses the rationale, structure, benefits, challenges, and future directions of multidisciplinary AF clinics, emphasizing their role in optimizing AF management.

ABSTRACT Bipolar disorder’s (BD) clinical heterogeneity has an unresolved genetic basis. We meta-analyzed genome-wide association studies (GWAS) of 16 BD subphenotypes in 226,032 individuals from 57 cohorts (38,022 cases); 10 advanced to multivariate and multi-trait analyses. Four factors (compulsive, psychotic, dysregulated, internalizing) explained 82.8% of shared genetic variance. BD1 and BD2 loaded on distinct factors despite a high genetic correlation; 87.0% of common-factor loci were significant in neither subtype. Unipolar mania aligned with psychosis over internalizing, and was distinguishable from BD1, and rapid cycling showed heritable cross-domain liability. We identified 356 risk loci, 158 novel, including the first univariate-GWAS associations for psychosis, unipolar mania, rapid cycling and schizoaffective disorder—and 249 credible genes (89 high-confidence), 12 with approved-drug or clinical-phase annotations. Cell-type association showed a midbrain dopaminergic–GABAergic gradient along the psychotic factor. BD’s genetic architecture appears hierarchical—a general liability resolving into dimensions of course and comorbidity beyond diagnostic subtypes.

Abstract Neurofibrillary tangles are dynamic neuropathologic hallmarks of Alzheimer’s disease with a hypothesized lifespan morphologically-defined by three maturity levels: pretangles, mature tangles, and ghost tangles. To better understand the progression of tangle pathophysiology, we characterized tangle maturity level predilection of 15 tau antibodies recognizing a broad range of linear, phosphorylation, conformational, and truncation epitopes in the hippocampus of 24 postmortem brains. We developed the tangle maturity scoring system to semi-quantitatively evaluate each tangle maturity level. Based on proportions of tangle maturity levels, we classified antibodies as “early” (mostly pretangles and mature tangles), “middling” (mature tangles with pretangles and ghost tangles), and “advanced” (mostly ghost tangles and mature tangles) tangle maturity markers. To summarize tangle maturity predilection, we developed the tangle maturity scale to integrate individual tangle maturity scores. Correlations showed stronger relationships between tangle maturity scale and subsector thickness for more advanced tangle maturity markers in CA1 and subiculum, whereas Braak tangle stage remained consistently correlated throughout markers of the tangle lifespan. To aid in scoring hippocampi, we used machine learning to recognize tangle maturity levels, which performed comparably to a domain expert and showed similar relationships by Spearman correlation. Pattern recognition software was used to assess tangle and neuritic tau burden separately, which generally correlated with Braak stage and neuronal counts. However, tangle-derived tau burden more consistently correlated with hippocampal subsector thickness. In conclusion, we developed manual and automated scoring systems to evaluate tangle maturity levels, demonstrating early 4R, phosphorylated, and oligomeric tau accumulation preceding more advanced 3R and truncated tau. Our study provides supportive evidence of disease-relevant ordering of tau posttranslational modifications in the brain, which may have implications for theragnostic development. These findings underscore the promise of computerized quantitative analyses (i.e., pathomics) for high-throughput feature extraction from whole-slide images to enhance our understanding of microscopically observed morphologic changes.

Abstract Background/Introduction Access to timely healthcare in disadvantaged areas remains essential to achieving equitable health outcomes, especially in regions facing structural and social vulnerabilities. Purpose To assess wait times for cardiovascular disease consultations in US-Mexico border regions compared to non-border regions among US Veterans. Methods This cross-sectional analysis included all veteran cardiovascular consultations referred through the Veterans Choice Program to community healthcare centers from 2014 to 2020. We obtained the average wait times in days for consultation approval, scheduling, completion, and total wait time from approval to consultation completion. All consultations were classified by county of residence as either within a US-Mexico border region or a non-border region, as per the La Paz Agreement. Multivariable linear regression analyses were performed to evaluate the impact of border status on average wait times. ARIMA modeling was completed to estimate forecasted wait times during the COVID-19 pandemic. Results A total of 485,158 consultations related to outpatient cardiovascular disease were retrieved from the VA Healthcare System. Amongst these, 461,696 of the consultations were placed in non-border regions whereas 23,462 consultations were placed in US-Mexico border regions. The most common consultation requests were made for general cardiology clinic (n=365,227), echocardiography (n=32,017), cardio-pulmonary rehabilitation (n=40,699), and cardiac stress testing (n=16,258). Wait times for cardiovascular disease consultations were not higher in US-Mexico border counties than in non-border regions. For electrophysiology consultations specifically, border counties exhibited significantly shorter total wait times (coeff = -10.81, p=0.008). Additionally, while the COVID-19 pandemic led to increased total wait times in non-border areas (Figure 1), total wait times in border regions remained stable during this period (Figure 2). Conclusions Our findings suggest that US-Mexico border region status does not result in longer wait times for cardiovascular disease consultations, with the exception of shorter wait times for electrophysiology services. This study provides important insights into the unique dynamics of healthcare access in structurally disadvantaged regions, highlighting that wait times are not a significant barrier to cardiovascular care in border areas, and emphasizes the need to consider regional differences in healthcare delivery policies.

Abstract RATIONALE:New-onset atrial fibrillation (NOAF) is a common arrhythmia associated with adverse outcomes in patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA). Both conditions, through shared mechanisms, raise the likelihood of NOAF incidence, emphasizing the importance of epidemiological data and preventive measures to prevent NOAF burden. Therefore, we examined the risk of NOAF in patients with COPD, OSA, and their overlap syndrome (OS). METHODS: We extracted data from the Banner Healthcare Organization, US Collaborative Network in TriNetX, identifying three patient cohorts using ICD-10 codes for COPD (J40-J44) and OSA (G47.3). This included 73,540 patients with OS, 198,880 patients with OSA only, and 337,010 patients with COPD only. Patients with a prior diagnosis of AF before their diagnosis of OSA or COPD were excluded. Propensity matching was conducted based on age, sex, ethnicity, and cardiovascular disease risk factors and prevalence including hypertension, tobacco use, dyslipidemia, obesity, and ischemic heart disease. We calculated the relative risk (RR), hazard ratio (HR), and 95% confidence intervals (CI) for incident AF among propensity score-matched cohorts, comparing OS with OSA alone and OS with COPD alone.RESULTS: In the OS vs. OSA only comparison, 63,070 patients were matched per cohort. Lifetime incidence of new AF was higher in the OS group (13.65%) compared to the OSA-only group (8.24%), with an RR of 1.66 [95% CI: 1.60-1.72]. Kaplan-Meier analysis indicated a lower AF-free probability in the OS group (65.96%) than in the OSA-only group (77.03%), with an HR of 1.56 (p &lt; 0.001). In the OS vs. COPD only comparison, 65,810 patients were matched per cohort. Incidence of new AF in the OS group was 13.76%, compared to 9.86% in the COPD-only group, with an RR of 1.40 [95% CI: 1.35-1.44]. Kaplan-Meier analysis showed a lower AF-free probability for the OS group (66.13%) versus the COPD-only group (78.94%), with an HR of 1.28 (p &lt; 0.001). Sensitivity analyses restricted to the first five years post-diagnosis revealed a persistently higher relative risk of incident AF in OS patients, with an RR of 1.67 [95% CI: 1.60-1.73] compared to OSA alone, and an RR of 1.34 [95% CI: 1.29-1.39] compared to COPD alone. CONCLUSION:We identified that patients with OS have a higher risk of NOAF compared to either condition alone. This emphasizes the need for vigilant monitoring and targeted interventions in patients with OS to decrease arrhythmogenicity risks.