Citations

Introduction: Carotid artery intraplaque hemorrhage (IPH) is increasingly recognized as a predictive marker of cerebrovascular events. Despite widespread utilization of contrast-enhanced CT angiography (CTA) for the evaluation of carotid atherosclerosis, diagnosis of IPH on CTA is challenging, limiting risk stratification capabilities. We evaluated convolutional neural networks (CNN) for detection of histology-proven IPH in carotid CTA. Methods: The study included carotid endarterectomy patients from our center who had preoperative CTA and available plaque specimens from the Mayo Clinic Carotid Artery Atherosclerosis Trial (MCAT) Biobank. A validated segmentation model localized common and internal carotid arteries (CCA/ICA). CCA bifurcation served as landmark after a large language model, Llama3.0-70B, verified culprit plaque proximity to the bifurcation from CTA reports. A 3×3×4cm box around ipsilateral CCA bifurcation was sampled from CTA volumes and images were labeled IPH by histology study of carotid specimen (Fig 1). Given limited cases with concurrent imaging and histology, we employed a robust cross-validation strategy: 22 cases (20%) held-out for testing, with remaining data 86 cases used for 5-fold cross-validation (stratified by IPH presence). The five resulting models independently generated IPH probability scores, and ensembled predictions calculated by three methods to enhance generalizability: Majority and weighted voting based on binary IPH class and soft voting based on IPH probability scores. Results: Of 418 patients with histological analysis, 130 had CTA studies available. After excluding 22 cases lacking histological consensus, 108 cases were analyzed. In the 22 test cases the mean age was 68.1±8.5 years and 59% were male; In the cross-validation folds age ranged from 67.1±6.9 to 75.3±7.6 years 56-82% were male. Individual models' performance on the test set showed mean ROC-AUC of 0.79 (95% CI: ±0.05) and average precision of 0.85 (±0.05) (Fig 2). The ensemble approach achieved superior performance with soft voting demonstrated 82% ROC-AUC, 77% accuracy, 79% precision, 85% sensitivity, and 82% F1-score for IPH detection, outperforming majority voting and weighted voting (Fig 3). Conclusion: Automated IPH detection in widely available CTA imaging can turn it to a powerful stroke risk assessment tool, supporting personalized prevention strategies and surgical decision-making, ultimately reducing cerebrovascular morbidity and mortality.

Background: Pathogenic variants in LMNA -encoded lamin A/C cause a genetic cardiomyopathy marked by conduction disease, atrial and ventricular arrhythmias, and systolic dysfunction. The mechanisms underlying phenotypic differences between Ig-like and coiled-coil domain missense variants remains unclear. Here, we developed a novel suppression-and-replacement disease modeling (SupRep-DM) platform to screen LMNA missense variant function and prioritize mechanistically informative phenotypes. Methods: LMNA-SupRep-DM is a dual-component lentiviral system that enables simultaneous knockdown of endogenous LMNA via an LMNA -targeted shRNA and replacement with an shRNA-immune mutant lamin A cDNA encoding the pathogenic variant of interest with HA-tag. HEK293T cells and iPSC-derived cardiomyocytes (iPSC-CMs) were transduced with 9 unique SupRep-DM constructs harboring variants in either the coiled-coil (E82K, K97E, R216C, H222P, T224I, R335W) or Ig-like (R471H, R541C, R541H) domains. Cells were stained using HA-specific antibodies, imaged by confocal microscopy, and analyzed for nuclear morphology, aggregate burden, and fluorescence intensity. Statistics: Dunnett’s test and one-way ANOVA. Results: In HEK293T cells, 8/9 LMNA variants significantly reduced nuclear circularity (p< 0.05), most notably in K97E (-11%, n=89), R471H (-12%, n=62), and R541C (-9%, n=104). Additionally, K97E increased nuclear area (+24%) and R541C decreased it (−29%) vs wild-type (WT, p<0.0001). Lamin A intensity was significantly reduced in K97E, R471H, and R541C, but increased in T224I and R335W vs WT. In iPSC-CMs, Ig-fold variants R541C and R541H significantly reduced nuclear circularity (−28%, –34%), increased elongation (+42%, +49%), and elevated lamin A aggregates ~4–5-fold vs WT (p≤0.0005). R471H and the coiled-coil variant E82K also increased aggregate burden, while the remaining variants (K97E, R216C, H222P, T224I, R335W) showed no significant effects in iPSC-CMs. Conclusions: LMNA missense variants cause domain-specific nuclear disruptions, with variants localizing to the Ig-like domain inducing nuclear deformities and consistent aggregation across both cellular models. Coiled-coil variants showed more variable, context-dependent effects. The more pronounced phenotypes in iPSC-CMs may reflect contraction-mediated stress absent in HEK293T cells. The SupRep-DM platform sensitively detects these structural changes, demonstrating its utility for mechanistic prioritization of LMNA variants.

Background: Pulsed Field Ablation (PFA) has gained widespread adoption for pulmonary vein isolation (PVI) due to its tissue selectivity and safety profile. However, its role in cavotricuspid isthmus (CTI) ablation for typical atrial flutter is less defined. This study compares CTI ablation using PFA versus radiofrequency ablation (RFA) in patients undergoing PVI exclusively with PFA. Research Question: We hypothesized that in patients undergoing PFA-based PVI, CTI ablation using PFA would reduce procedure and fluoroscopy times without increasing complication or flutter recurrence rates compared to RFA. Methods: We retrospectively analyzed patients who underwent CTI ablation with either PFA or RFA alongside PFA PVI between 2024 – 2025 across all Mayo Clinic sites. Baseline characteristics, procedural parameters, acute success, and 12-month arrhythmia recurrence were compared between groups. All patients received standard follow-up, including ECGs and Holter monitoring. Results: A total of 350 patients were included (CTI PFA: n = 126; CTI RFA: n = 224). Patients in the PFA group were older (68.8 ± 8.5 vs. 65.7 ± 10.1 years; p <0.01) and had higher CHA2DS2-VASc scores (2.84 ± 1.57 vs. 2.45 ± 1.45; p = 0.02). Fluoroscopy (18.9 ± 9.1 vs. 25.2 ± 23.3 min; p < 0.01 ) and procedure times (172.6 ± 22.4 vs. 224.7 ± 74.2 min; p < 0.01) were significantly lower in the PFA group. Complication rates (8.7% vs. 4.9%; p = 0.15) and typical flutter recurrence (3.1% vs. 1.7%; p = 0.46) were similar between groups during a mean follow-up of 125 days. Conclusion: In patients undergoing PVI with PFA, CTI ablation using PFA is associated with significantly reduced procedure and fluoroscopy times compared to RFA, without increased complications or arrhythmia recurrence. These findings support the feasibility and efficiency of PFA for typical flutter ablation when performed during PFA-based AF procedures.

Background: Mixed venous oxygen saturation (SVO2), a direct marker of circulatory adequacy measured in the pulmonary artery, has been proposed as a more immediate reflection of perfusion compared to serum lactate, which can be delayed due to clearance variability and lab turnaround. While central venous oxygen saturation (ScVO2) is commonly used in shock management, data on the prognostic value of SVO2 remains inconsistent. This study evaluates whether trends in SVO2 and lactic acid over 72 hours are associated with ICU mortality, and whether monitoring SVO2 offers clinical benefit. Methods: From the MIMIC-IV ICU database (n=34,222), 3,149 patients with SVO2 measurements were included. Patients were stratified into four groups based on SVO2 and lactate trends from ICU admission to 72 hours: SVO2 Groups: BB: Below–Below: SVO2 <55% at both timepoints (q1: 51%, q3: 60%) BA: Below–Above: SVO2 <55% initially, improved to >65% (q1: 58%, q3: 68%) AA: Above–Above: SVO2 ≥65% consistently (q1: 72%, q3: 79%) AB: Above–Below: SVO2 >65% initially, dropped to <55% (q1: 62%, q3: 72%) Lactic Acid Groups: BB: Below–Below: <2 mmol/L throughout (q1: 1, q3: 1.6) BA: Below–Above: <2 initially, rose to >2 (q1: 1.5, q3: 2.8) AA: Above–Above: >2 consistently (q1: 2.6, q3: 5.4) AB: Above–Below: >2 initially, fell to <2 (q1: 1.6, q3: 2.9) We then constructed a heat map to compare %mortality at 30 days in these groups. Results: The highest mortality (100%) occurred in patients with persistently elevated lactate (>2 mmol/L) and low SVO2 (<55%) (group 3a). The second-highest mortality (75%) was observed in those with persistently elevated lactate but improved SVO2(3c). Notably, among patients with improved lactate, mortality was similar regardless of whether SVO2 improved or remained low ($a vs 4c). This suggests that lactic acid trends may be a more reliable prognostic marker than SVO2. Conclusion: Improvement in SVO2 over 72 hours does not necessarily correlate with improved ICU survival. Persistent hyperlactatemia remains a stronger predictor of mortality. These findings question the clinical utility and cost-effectiveness of routine SVO2 monitoring in ICU settings.

Background: Cardiac amyloidosis (CA) patients with reduced left ventricular ejection fraction (EF) are at increased risk for mortality. The benefit of cardiac resynchronization therapy (CRT) in terms of mortality reduction has not been established in this population. Aim: To evaluate the survival benefit of CRT, either CRT-D or CRT-P, in a large cohort of patients with cardiac amyloidosis and reduced EF. Methods: We retrospectively analyzed patients with confirmed CA and reduced EF (<40%) between 2009 and 2023 across Mayo Clinic sites. Patients were stratified into three groups: no device, CRT with pacemaker function (CRT-P), and CRT with defibrillator function (CRT-D). CRT devices were indicated for low ejection fraction less than 40% and patients who had chronic heart failure with a wide QRS. Kaplan-Meier survival estimates were generated, and log-rank tests were used for comparison. A secondary analysis was conducted combining CRT-P and CRT-D versus no device (EF <40%), and a tertiary analysis compared CRT-P versus CRT-D. Results: Among 184 patients [36 AL (20%), 148 ATTR (80%)], 38 (19%) had no cardiac device and EF <40%, 20 (11%) received CRT-P, and 116 (63%) received CRT-D. The median follow-up was 3.4 years (1.7, 5.0). The probability of survival was significantly higher in the CRT group compared to the no device-EF<40 group (Log Rank p=0.013; figure B). Among patients receiving CRT, there was no significant difference in all-cause mortality between those receiving CRT-P and those receiving CRT-D (Log Rank p=0.5; figure C). Conclusion: In patients with cardiac amyloidosis and reduced EF, CRT is associated with significantly improved survival compared to no device. No mortality difference was observed between CRT-P and CRT-D. Prospective studies are warranted.

Background: Patients with systemic right ventricle (sRV), including congenitally corrected transposition of great arteries (cc-TGA) and dextro-transposition of great arteries (d-TGA) post-atrial switch procedure are at risk of sudden cardiac death due to ventricular arrhythmias (VA). While programmed ventricular stimulation (PVS) can help with risk stratification in certain patients with congenital heart disease, its role in sRV is unknown. Objective: To study the diagnostic value of electrophysiology study (EPS) in predicting VAs in patients with sRV. Methods: EPS was performed in 53 patients with sRV at Mayo Clinic from 1994 to 2021. Patients with a history of sustained VA or cardiac arrest were excluded (n=19). The incidence of sustained VA (sudden cardiac death, sustained ventricular tachycardia [VT] or appropriate implantable cardioverter-defibrillator [ICD] therapy) was evaluated in the remaining 34 patients. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of EPS in predicting VAs is reported. Results: The mean age at EPS was 36.2±11.6 years, 21 (61.8%) were male, 21 (61.8%) had d-TGA and mean sRV ejection fraction was 31.3±10.8%. Indication for EPS was supraventricular tachycardias (n=15, 44.1%), syncope/palpitations (n=9, 26.5%) and non-sustained VT (n=6, 17.6%). 13/34 (38.2%) patients had inducible sustained VA, (5 [38.5%] with monomorphic VT and 8 [61.5%] with polymorphic VT/VF). Treatments included ICD implantation in all 13 patients and ablation in one patient. During a mean follow-up of 8±5.4 years, one patient with a positive PVS (inducible polymorphic VT) experienced sustained VT secondary to atrial flutter with 1:1 conduction. The sensitivity of PVS was 100%, specificity was 63.6%, PPV 7.7%, and NPV 100%. Conclusion: In this retrospective cohort of patients with sRV, polymorphic VT was the most commonly observed VA during PVS. The predictive value of a positive PVS was low in this cohort, and larger studies are needed to better define the role of EPS in risk stratification. Patients with negative EPS did not have future VAs recognizing that the overall event rate is low. Further multicenter research with a larger sample is required to develop predictive models to identify those at risk of VAs.

Background: Stroke is a devastating complication of transcatheter aortic valve replacement (TAVR). Cerebral embolic protection devices (CEPD) have been introduced to reduce TAVR-related stroke by capturing or deflecting debris during the procedure. While these devices can capture embolic material, their clinical benefit in preventing stroke remains uncertain. We aimed to determine whether the use of CEPD during TAVR reduces the incidence of periprocedural stroke. Methods: We performed a systematic review and meta-analysis of studies comparing TAVR with versus without CEPD. We searched PubMed, Embase, and ClinicalTrials.gov for RCTs (randomized controlled trials) comparing CEPDs to no protection in TAVR patients from 2011 to May 2025. Nine RCTs involving a total of 11,608 patients (CEPD group n=5,953; control n=5,655) were included. Stroke outcomes were defined according to Valve Academic Research Consortium-2 (VARC-2) criteria and categorized as- all stroke, disabling stroke, or non-disabling stroke. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using a fixed-effects model. Heterogeneity also was measured. Results: Stroke rates were low and did not differ significantly between the CEPD (n=343) and control (n=319) groups. The incidence of all strokes was 1.96% with CEPD vs 1.88% without CEPD (RR 0.97, 95% CI 0.75–1.15; p=0.50). Disabling stroke occurred in 0.79% of CEPD patients vs 0.95% of controls (RR 0.79, 95% CI 0.57-1.10; p=0.16). Non-disabling stroke occurred in 1.26% of patients in both groups (RR 1.06, 95% CI 0.8 -1.40; p=0.64). There was no significant heterogeneity across trials is (0) for all endpoints. Notably, the largest trial in the analysis (BHF PROTECT-TAVI, n=7,635) showed no difference in stroke rates with CEPD, aligning with the overall results. Subgroup analyses revealed a trend toward fewer disabling strokes with CEPD use, but this trend was not statistically significant. Conclusion: We found no significant stroke risk reduction with the use of CEPDs during TAVR. While a trend toward fewer disabling strokes was observed, it was not statistically significant. Routine use of CEPDs is not supported, and selective use in high-risk patients warrants further large RCTs.

Background: Older adults with severe aortic stenosis (AS) are at high risk of mortality unless treated by aortic valve replacement (AVR). The Society of Thoracic Surgery (STS) score is primarily used clinically to determine mortality risk from surgical AVR. Due to geriatric comorbidities unique to older adults, traditional methods of risk stratification with STS may have significant shortcomings. Administratively derived risk scores that have prognostic significance in the geriatric population may prove valuable. Methods: We reviewed patients at our hospital system with AS undergoing AVR (surgical and transcatheter) and administratively derived an Elder Risk Assessment (ERA) score from the health record. The ERA score is a composite of age, marital status, number of hospitalized days in previous 2 years, and comorbidities (diabetes, coronary artery disease (CAD), heart failure, stroke, pulmonary disease, cancer, and dementia). Kaplan-Meier method was used to estimate survival by ERA score tertile. Cox regression was used to determine association between ERA and survival after accounting for STS predicted risk. Results: There were a total of 228 patients that underwent AVR (TAVR: 59 (26.1 %); SAVR 167 (73.9%) and had ERA scores derived. The average age was 79.6 (SD 7.6) years) and there were 93 (40.8%) women. Patients were stratified by ERA score tertiles: low (≤6), mid (6-13), or high (≥14). Over a mean follow up of 5.8 (SD 3.1) years, lower ERA scores were associated with better long-term survival (p<0.001). After accounting for age, sex, and STS score, mid ERA (HR 1.61; 95% CI 1.00-2.59; p<0.001) and high (HR 2.90; 95% CI 1.79-4.69; p<0.001) were associated with mortality (reference: low ERA). For every 10-point increase in the ERA, there was a 2-fold increase in adjusted mortality risk (HR 2.14; 95% CI 1.58-2.90; p<0.001). Conclusions: Older adults undergoing AVR for severe AS have specific geriatric comorbidities that may be better characterized using the ERA score. This administratively derived score was independently associated with survival after accounting for the widely used STS risk score.

Backround: Atrial fibrillation (AF) is a common complication following veno-venous extracorporeal membrane oxygenation (VV-ECMO), leading to further complications from anticoagulation or stroke. The Artificial Intelligence AF Prediction Dashboard developed at Mayo Clinic generates two predictive outputs: (1) a continuous probability score and (2) a binary threshold-based signal to predict the likelihood of AF at an individual level after 12-lead electrocardiogram (ECG) is obtained. Using both continuous risk (%) and binary (yes/no) likelihood, we present a novel method to understand AF risk after VV-ECMO cannulation based on pre-ECMO 12-lead ECG. Methods: We reviewed a total of 147 patients on ECMO between 2018 and 2024, from which 85 VV-ECMO patients with complete data were included. AI Dashboard outputs were quantified as binary (1/0) or percent likelihood for AF. R was utilized for statistical analysis. Results: 85 patients met our inclusion criteria from which AF after cannulation occurred in 31 (36%). 17 patients had a history of AF prior to VV-ECMO initiation. The mean age of our cohort was 49 years with a mean BMI of 29.3. Baseline AI Dashboard continuous assessment identified 39 patients (46%) compared to the binary assessment identifying 31 patients (36%). Logistic regression in the binary assessment demonstrated an odds ratio of 1.08 (95% CI 1.04 – 1.12) with a p value of <0.001. The binary AF Prediction yielded a 58% sensitivity, 76% specificity, 58% PPV, and 76% NPV, with an accuracy of 67%. The continuous AF Probability score achieved 72% balanced accuracy with sensitivity 74%, specificity 70%, PPV 59% and NPV 83%, indicating fair overall performance and suggesting good utility for ruling out AF in low-risk patients. Although both outputs provided moderate predictive accuracy, the continuous score reported before ECMO cannulation demonstrated stronger overall performance with fewer false negatives and higher rule-out value. Conclusions: We demonstrate the novel use of an AI predictive model in the VV-ECMO population for the prediction of AF risk with both continuous and binary risk cutoffs from baseline ECG. This data highlights the need for further development in ECMO-specific AI models to help mitigate risk after the onset of atrial arrhythmias. As AI-driven tools become increasingly integrated into care, their performance must be continuously validated and recalibrated for specific populations to ensure their safe and effective use.

Introduction: Peripheral Arterial Disease (PAD) is a prevalent condition associated with considerable morbidity and mortality, a burden that is further intensified by the frequent co-occurrence of hypertension. The coexistence of these conditions not only amplifies cardiovascular risks but also complicates clinical management, thereby contributing to elevated mortality rates. Although their correlation is well understood, mortality trends in United States have not been studied. Methods: This study utilized International Classification of Diseases, 10th Revision (ICD-10) codes to extract age-adjusted mortality data for individuals with PAD and hypertension from the CDC WONDER (Center for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) cohort. The overall sample and subgroups defined by demographics (age, sex, race/ethnicity) and region (state, census and urban-rural status) were analyzed. Trends in mortality were quantified by computing associated annual percentage changes (APC) using Joinpoint Regression Program Version 4.9.0.0 trend analysis software. Results: A total of 540954 deaths were observed, of which 260517 were men (48.2%). Overall, the age-adjusted mortality rates (AAMR) exhibited a sharp increase from 1999 to 2001 (APC:25.3; 95% CI: -0.36,56.2), followed by a sustained decrease until 2017 (APC: -2.16; 95% CI: -11.1, -1.52), after which a notable upward trend was observed (APC:9.38; 95% CI: -0.38,24.1). A similar AAMR trend was seen on gender-based subgroup analysis with male patients showing the highest AAMR 13.5 (95% CI: 13.1,13.7) in 2020. Amongst all racial groups, Black or African American showed the highest 14.9 (95% CI: 14.8-15) while Asian or Pacific Islander showed the lowest 5.8 (95% CI: 5.7-5.9) AAMR over 2 decades. The West region had the highest overall age-adjusted mortality rate (AAMR) of 10.2 (95% CI: 10.2-10.3). Among individual states, Vermont displayed the highest AAMR, reaching 15.8 (95% CI: 15.1-16.5). Conclusion: Healthcare disparities are evident. The unprecedented recent increase in mortality rates, following years of successful decline, necessitates a thorough evaluation of healthcare policies and PAD treatment advancements to identify the causative factors behind this trend reversal.