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Background: Loeys-Dietz syndrome (LDS) and vascular Ehlers-Danlos syndrome (vEDS) are rare connective tissue disorders characterized by arterial fragility and early-onset vascular events. Stroke risk is elevated in both conditions, but data on stroke subtypes and anticoagulation use remain limited. Understanding the relationship between stroke mechanisms, arrhythmias, and antithrombotic therapy is crucial in these genetically vulnerable populations. Aim: To assess the prevalence and subtypes of stroke in patients with LDS and vEDS. Methods: A retrospective chart review was conducted across three Mayo Clinic sites. Patients with LDS and vEDS were identified using an electronic data extraction tool, followed by manual chart review for diagnostic confirmation. Stroke subtypes, ischemic, dissection-related, and hemorrhagic, were classified based on imaging findings and clinical documentation. Data on atrial arrhythmias, valve replacement status, and anticoagulation use (including warfarin and apixaban) were systematically collected and analyzed. Results: In the LDS cohort, 12 of 94 patients (12.8%) experienced a stroke: 8 ischemic (8.5%), 3 dissection-related (3.2%), and 1 hemorrhagic (1.1%). Atrial fibrillation or flutter was present in 7 patients (58.3%), 6 of whom had ischemic strokes. Among the stroke patients, 9 (75%) had prosthetic valves, 6 mechanical and 3 bioprosthetic, and 4 (33.3%) were on warfarin at the time of the event. In the vEDS cohort, 22 of 132 patients (16.7%) had strokes: 13 ischemic (9.8%) and 9 dissection-related (6.8%). No hemorrhagic strokes were observed. Atrial fibrillation or flutter was documented in 12 patients (54.5%), with 10 experiencing ischemic and 2 dissection-related strokes. Of these, 5 (22.7%) were on apixaban, 3 (13.6%) on warfarin, and 4 (18.2%) were not anticoagulated. None of the vEDS stroke patients had mechanical valves. Conclusion: Ischemic stroke is the most frequent cerebrovascular event in both LDS and vEDS, but dissection-related strokes are more common in vEDS. Atrial arrhythmias often precede ischemic events, yet anticoagulation use varies widely. One-third of dissection-related strokes occurred despite antithrombotic therapy, raising concerns about current management strategies. These findings support the need for syndrome-specific guidelines for stroke prevention, arrhythmia management, and anticoagulation in LDS and vEDS patients.

Background: Spontaneous coronary artery dissection (SCAD) is increasingly recognized as a cause of acute coronary syndrome, particularly in young to middle-aged women. While most presentations are associated with preserved left ventricular ejection fraction (LVEF), a subset of patients present with acute systolic dysfunction. The characteristics of patients who recover their LVEF are not clearly defined. Methods: We retrospectively analyzed 495 patients with angiographically confirmed SCAD treated at three Mayo Clinic sites (Arizona, Rochester, and Florida) from 1994 to 2023. Patients with a prior history of myocardial infarction, coronary artery disease, and congenital heart disease were excluded. Baseline LVEF at SCAD presentation was categorized into <35%, 35–39%, 40–49%, and ≥50%. Follow-up LVEF was assessed by echocardiography performed between 30 days and 1 year post-SCAD. The primary outcome was improvement in LVEF to ≥50% at follow-up. Results: A total of 495 SCAD patients were included. At presentation, 26% had reduced LVEF: 6% had LVEF <35%, 5% had LVEF between 35–39%, and 15% had LVEF between 40–49%. Patients who did not normalize their EF at follow-up were slightly younger (45 vs. 48 years, p=0.04), were more likely to have had an in-hospital cardiac arrest (13% vs. 4%, p=0.01), required mechanical circulatory support during their care, and had SCAD involving the left main artery (11% vs. 2%, p=0.01). Predictors of EF normalization included SCAD which involved the obtuse marginals (15% vs. 4%, p<0.05). The group with the lowest EF at presentation had the highest probability of persistent EF <50% at follow-up (32% for those with LVEF <35%) while patients who had normal EF at presentation had a 6% chance of having EF <50% at follow-up (Figure 1). Conclusions: Our study shows that the majority of SCAD patients have normal EF at presentation. 80% of those with reduced EF at presentation will normalize at follow-up. Predictors of low EF at follow-up included dissection involving the left main artery, lower EF at SCAD presentation, in-hospital arrest and use of mechanical circulatory support.

Background: A key determinant of prognosis in pulmonary hypertension (PH) is the right ventricle’s (RV) ability to adapt to increased pulmonary vascular resistance. Consequently, markers of RV-pulmonary artery (PA) coupling may improve prognostic prediction in PH. The ratio of tricuspid annular plane systolic excursion (TAPSE) to systolic PA pressure (sPAP) has been proposed as a surrogate for RV-PA coupling and a reliable prognostic marker, however, the existing data on the prognostic value of the ratio between RV longitudinal strain (RVLS) and sPAP as a surrogate for RV-PA coupling is scarce. Hypothesis: To evaluate the prognostic role of RVLS/RVSP in PH patients and to compare this novel marker with established markers of RV-PA coupling. Methods: This is a single-center study that included adult patients with PH classified as group I or IV, all of whom had undergone a transthoracic echocardiogram (TTE) within one year prior to the initiation of PH-specific treatment. Certified sonographers procured RV strain measurements using a specific software (Epsilon Imaging, Ann Arbor, MI). Receiver operating characteristic (ROC) analysis was used to determine the best cutoff for predicting all-cause mortality at one-year for RVLS/RVSP and TAPSE/RVSP. The association of RVLS/RVSP and TAPSE/RVSP with mortality at one year was assessed using the Kaplan-Meier analysis and multivariate Cox regression analysis (adjusted for REVEAL LITE 2.0 risk score). Results: A total of 160 patients were included with a median age of 67.2 (56.8, 73.7) years and 47 (29.2%) were male . ROC analysis revealed optimal cutoffs of 0.265 (AUC = 0.83) for RVLS/RVSP and 0.185 (AUC = 0.77) for TAPSE/RVSP to predict all-cause mortality at one year. One-year cumulative incidence of all-cause mortality was lower among patients with RVLS/RVSP ≥ 0.265 (0 % vs 13.7 %, p = 0.001) and patients with TAPSE/RVSP ≥ 0.185 (1.8 % vs 16.7 %, p = 0.001) (Figure 1) . In the multivariate analysis, RVLS/RVSP < 0.265 was associated with higher risk of mortality at one year (HR: 2.38, 95 % CI: 1.05 to 5.38, p = 0.036) while TAPSE/RVSP < 0.185 was not (HR: 2.01, 95 % CI: 0.93 to 4.31, p = 0.072). Conclusions: RVLS/ RVSP may be a valuable prognostic marker in PH patients and could outperform conventional TTE parameters as a surrogate for detecting RV-PA coupling.

Introduction: Placental dysfunction is an emerging contributor to neonatal morbidity and mortality in pregnancies complicated by fetal congenital heart disease (CHD). Previous work in mouse models of CHD and examination of human placental pathology indicates that the maternal-fetal interface, specifically the syncytiotrophoblast layer, can be dysmorphic in fetal CHD-affected pregnancies. We hypothesized that gene expression in a subset of placentas affected by fetal CHD would show differences in genes required for syncytiotrophoblast differentiation and function. Methods: Placentas from pregnancies affected by fetal CHD were sampled and stored as formalin-fixed paraffin embedded blocks per pathology core standard protocol. A subset of fetal CHD cases affected by left ventricular outflow tract obstruction (LVOTO) without genetic diagnoses or major extracardiac anomalies were selected for transcriptomic analysis. Results: Placentas affected by fetal LVOTO (n=20) demonstrated markedly reduced expression of genes associated with terminally differentiated syncytiotrophoblasts compared to controls (n=10). Specifically, aromatase (p<0.0001), placental growth hormone (p<0.0001), and multiple chorionic gonadotropin subunits and pregnancy specific glycoproteins were downregulated. Transcription factor GCM1, a master regulator of trophoblast differentiation, was also downregulated (p<0.0001). Syncytin-1, a product of syncytiotrophoblasts that facilitates their formation from cytotrophoblasts, was downregulated (p<0.0001) and syncytin-1 receptor expressed on cytotrophoblasts was upregulated (p<0.0001) in the LVOTO affected placentas. Abundance of cytotrophoblasts did not differ between groups, which showed similar expression of cytotrophoblast markers including E-cadherin and cytokeratins. Conclusions: Dysregulation of the heart-placenta axis in fetal CHD may be a result of altered syncytiotrophoblast differentiation, resulting in decreased functional surface area at the maternal-fetal interface.

Introduction: Higher mtDNA-CN reflects better mitochondrial function, while lower levels indicate mtDNA release and increased inflammation. Although mtDNA-CN serves as a marker of cardiovascular health, the importance and mechanism of risk associated with mtDNA in high-risk individuals with chronic coronary artery disease (CAD) remains poorly understood. To address this gap, we leveraged the ISCHEMIA Biorepository to: (1) evaluate the association between mtDNA-CN and all-cause death (ACD); and (2) define a transcriptomic profile associated with high mtDNA-CN and ACD risk for high-risk patients with CAD. Hypothesis: Higher mtDNA-CN is associated with reduced ACD risk and inflammation in high-risk patients enrolled in the ISCHEMIA Biorepository. Methods: Low pass whole genome sequencing and whole blood RNA-Seq were performed on 594 ISCHEMIA and ISCHEMIA-CKD participants with moderate-severe ischemia. Data were processed using the NYU deciphEHR pipeline and mtDNA was quantified using mitoAnalyzer. mtDNA-CN was median split, with samples having values ≤ median classified as the 'low' group and those > median as the 'high' group. Unadjusted group differences were assessed using Chi-squared tests. Survival analysis was performed using Cox proportional hazard models, adjusted for age, sex, diabetes, eGFR, dialysis status, ischemia severity, and left ventricular ejection fraction. Adjusted differential gene expression (DGE) and gene set enrichment analysis (GSEA) were performed to explore molecular mechanisms underlying mtDNA-CN. Results: Median age was 67 (IQR: 57–78); 19% were female, 84% white, and 6% Hispanic. Hypertension (84%), diabetes (43%), and obesity (45%) were common; 26% had eGFR <60 mL/min/1.73 m 2 . Median mtDNA-CN was 153 counts per sample. After multivariate adjustment , mtDNA-CN > median was associated with a 48% reduction in ACD (aHR = 0.52, 95% CI: 0.30–0.90; P = 0.020) (Figure 1A) . DGE revealed downregulation of inflammatory genes in the mtDNA-CN group, including S100A9 (FC=-.41, p=3.32e-10) and S100A12 (FC=-.56, p=3.32e-10). Inflammatory pathways such as the inflammasome complex (NES=-2.17, p=9.32e-03) and interleukin-1 production (NES= -2.02, p=6.60e-03) were downregulated among participants in the high mtDNA-CN ( Figure 1B) . Conclusion: Higher mtDNA-CN is associated with lower risk of ACD and reduced inflammasome activity, suggesting that enhanced mitochondrial health may mitigate inflammasome-related pathology linked to ACD in patients with CAD.

Introduction: Chronic total occlusion (CTO) is commonly encountered in patients with coronary artery disease and is associated with adverse outcomes, including increased short- and long-term mortality. While percutaneous coronary intervention (PCI) has shown potential clinical benefits in CTO patients, its comparative effectiveness against optimal medical therapy (OMT) remains debated. This meta-analysis aims to evaluate the impact of CTO-PCI versus OMT on key cardiovascular outcomes. Methods: We conducted a comprehensive search of Pubmed, Scopus, Web of science and Cochrane. We assessed outcomes including all-cause mortality, cardiac death, myocardial reinfarction, major adverse cardiac events (MACE), stroke, and repeat revascularization. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Statistical significance was defined as p<0.05. Results: 25 studies with a total of 22102 patients were included. Compared to OMT alone, CTO-PCI was associated with a significant reduction in the overall all-cause mortality (RR: 0.66; 95% CI: 0.53–0.82; p=0.0002), cardiovascular mortality (RR: 0.65; 95% CI: 0.52–0.82; p=0.0003) and MACE (RR: 0.84; 95% CI: 0.71–0.98; p=0.03). No statistically significant differences were observed between CTO-PCI and OMT in rates of Stroke (RR: 1.01; 95% CI: 0.68–1.50; p=0.96), Subsequent PCI/CABG (revascularization) (RR: 1.01; 95% CI: 0.78–1.29; p=0.97) or Heart Failure Hospitalization (RR: 0.77; 95% CI: 0.37–1.59; p=0.48) Conclusion: This is the largest and most updated systematic review meta analysis for CTO-PCI vs OMT. Our findings show that CTO-PCI is associated with significantly lower all-cause and cardiovascular mortality compared to OMT. However, no significant differences were observed between the two strategies in the incidence of stroke, need for subsequent revascularization (PCI/CABG), or heart failure hospitalization.

Subclavian artery stenosis is a rare but clinically significant cause of vertebrobasilar insufficiency and upper extremity ischemia. Management is challenging, especially in the presence of heavily calcified lesions. Intravascular lithotripsy (IVL) is an emerging adjunctive therapy for calcified lesions, primarily studied in coronary and lower extremity vessels, but its application in subclavian interventions is underexplored. A 78-year-old female with a history of hypertension, diabetes, hyperlipidemia, and peripheral artery disease presented with recurrent dizziness and nausea. Carotid duplex demonstrated moderate left internal carotid stenosis and retrograde flow in the left vertebral artery, consistent with subclavian steal syndrome. Subsequent angiography revealed 90% eccentric, calcified stenosis of the proximal left subclavian artery. Given the lesion’s heavy calcification, the patient underwent percutaneous intervention with a Serranator scoring balloon, followed by IVL using an 8x30 mm peripheral balloon (2 rounds, 30 pulses each). This resulted in significant lesion modification and relief of balloon waist. A 7x27 mm Express LD bare-metal stent was then deployed with excellent angiographic results and residual stenosis <10%. IVUS confirmed adequate stent expansion. The procedure was performed via right femoral access with no complications. Post-procedure, the patient reported complete resolution of dizziness and no further symptoms of vertebrobasilar insufficiency. She was discharged on dual antiplatelet therapy for 30 days, followed by aspirin monotherapy. At 1-month follow-up, she remained asymptomatic with a patent stent and no evidence of restenosis. This case highlights the utility of IVL in treating severely calcified subclavian artery stenosis. Traditional balloon angioplasty and stenting in such lesions are associated with suboptimal expansion, risk of dissection, and restenosis. IVL offers a safe and effective means of calcium modification, facilitating optimal stent deployment. To our knowledge, reports of IVL use in subclavian arteries are scarce, and this case adds to the growing body of evidence supporting its application in complex peripheral vascular interventions. IVL is a valuable adjunct in the endovascular management of heavily calcified subclavian artery stenosis, enabling successful stent placement and symptomatic relief. Further studies are warranted to define its role in this vascular territory.

BACKGROUND: The association between breast cancer diagnosis, treatment, and the risk of incident ischemic stroke remains unclear. We aimed to investigate ischemic stroke risk among breast cancer survivors and evaluate the association by age, follow-up duration, and cancer treatments. METHODS: Using the Korean National Health Insurance Service database, we studied 113,232 women newly diagnosed with breast cancer (aged ≥18 years) without prior stroke history who underwent breast cancer surgery between January 2010 and December 2016. Each was matched 1:3 by birth year to a cancer-free female population (n=322,818). Subdistribution hazard ratios (sHRs) and 95% confidence intervals (CIs) were estimated, accounting for death as a competing risk and adjusting for sociodemographic factors and cardiovascular and noncardiovascular comorbidities. RESULTS: Over a mean follow-up of 7.2 years, ischemic stroke occurred in 1,155 (1.0%) breast cancer surgery survivors. Overall, breast cancer survivors had a slightly lower risk of stroke than cancer-free women (sHR 0.94; 95% CI 0.88–1.00). However, stroke risk was elevated in the short term following diagnosis (sHR 1.59, 95% CI 1.34–1.89 at 1 year; sHR 1.17, 95% CI 1.05–1.30 at 3 years) across all age groups, with stronger associations observed at 3 and 6 months post-diagnosis. A reduced risk was observed after 1 year in a landmark analysis that included only individuals event-free at the 1-year follow-up (sHR 0.87, 95% CI 0.81–0.93). Among breast cancer survivors, treatment with anthracycline (sHR 1.25) and the combination of tamoxifen and aromatase inhibitors (sHR 1.49) were associated with increased stroke risk, whereas radiation therapy was associated with decreased risk (sHR 0.84). These associations weakened and became nonsignificant after 1 year. Stroke risk was also higher in breast cancer survivors with low income, hypertension, diabetes, or current smoking. CONCLUSION: The association between breast cancer and ischemic stroke risk is time-dependent, with increased short-term risk post-diagnosis and treatment, followed by a decline over time. These findings highlight the importance of proactive stroke risk management, including baseline cardiovascular assessments and ongoing monitoring for thromboembolic events.

BACKGROUND: Hypertension, the leading cause of cardiovascular mortality, remains suboptimally controlled. Large language models (LLMs) could improve hypertension control by augmenting clinical decision-making, but their reliability for guideline-driven tasks is unverified. This study evaluated the accuracy and safety of hypertension management recommendations generated by 3 LLMs. METHODS: Fifty-one vignettes were constructed and submitted to the LLMs (GPT-4, Gemini, Medical Large Language Model [by Google; MedLM]) and a hypertension expert to generate the responses. Three blinded reviewers rated each response on a 4-point accuracy scale, a binary safety (safe/unsafe) scale, and attempted to identify the source (LLM versus expert) providing the response. RESULTS: GPT-4 had the highest accuracy (83%) and safety (86%) scores among LLMs but remained inferior to expert responses (92% accuracy, 93% safety). Gemini and MedLM performed significantly worse (accuracy: 64% and 35%; safety: 73% and 39%, respectively). GPT-4 generated the most guideline-concordant responses (46%) among the 3 LLMs (Gemini 35%, MedLM 14%) but was lower than expert responses (68%). Interrater reliability for accuracy ratings was higher for LLM-generated responses (GPT-4 [intraclass correlation coefficient, 0.30], Gemini [intraclass correlation coefficient, 0.61], and MedLM [intraclass correlation coefficient, 0.58]), with lower agreement for expert responses (intraclass correlation coefficient, 0.23). A similar pattern was observed for safety and source discrimination ratings. The agreement was strongest for safety assessments and weakest for source discrimination. CONCLUSIONS: Among the 3 tested LLMs, GPT-4 demonstrated closer agreement to expert decisions, thereby showing greater potential for supporting hypertension management. Despite their potential, current LLM versions are inferior to expert recommendations. Human-in-the-loop supervision remains essential when deploying LLMs for clinical decision-making.

Background: Mechanical support strategies used for patients in shock prior to heart transplantation (OHT) correlates with post-transplant outcomes. OHT timing in patients supported by Impella 5.5 remains an evolving decision point, influenced by patient stability and donor logistics. With the emergence of organ transport technologies, we sought to determine whether the choice of system was associated with variations in pre-transplant support duration. Method: A retrospective review between Jan 2020 and May 2025 was completed. Patients were categorized by donor transport technology: traditional cooler, Organ Care System (OCS), or SherpaPak. The primary outcome was duration of Impella support (days) prior to transplant. Group-wise comparisons were performed using Kruskal-Wallis testing. Result: A total of 129 patients were assessed across three transport methods: traditional cooler:12, OCS: 35, SherpaPak: 84. Median age at transplant was 58 (51-65) years with EF of 17% (15-22). Cold ischemic time differed significantly across transport technologies (Kruskal-Wallis H = 77.4, p < 0.001) and was longest in OCS cases (417 min), compared to SherpaPak (236 min) and traditional cooler (234 min). The median duration of Impella support prior to OHT was 27 days for organs transported via traditional cooler, 25 days for those using OCS, and 28.5 days for SherpaPak with near-significant difference by transport method (H=5.77, p=0.056). There was no significant difference of rejection within the first year after OHT. Conclusion: Donor transport technology choice may serve as a surrogate for broader transplant logistics and selection strategies as evidenced by significant differences in ischemic time and near-significant trends in Impella support duration.