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Background: Current guidelines recommend prophylactic beta-blocker therapy for all genotype-positive newborns with long QT syndrome (LQTS), despite the potential for QT normalization in the first few weeks of life and the rarity of cardiac events during infancy. We previously reported our early experience with intentional non-therapy (INT) for low-risk adolescents and adults. Objective: To evaluate our single-center experience regarding INT for infants with genotype-positive LQTS identified following family screening/cascade testing. Methods: We retrospectively reviewed all infants diagnosed with genotype-positive LQTS between 2015 and 2024. Only LQTS patients with clinical and ECG data within the first 2 years of life and follow-up were included. INT was defined as adherence to precautionary QT-preventative measures and structured periodic follow-up rather than treating with prophylactic drugs, devices, or denervation. Candidacy for INT was based on absence of symptoms, down-trending QT during first few weeks of life, family agreement with the strategy, and frequent surveillance (e.g., ECG and Holter every 6 months). Prophylactic drug therapy was initiated if a surveillance QTc exceeded 470ms on 2 consecutive ECGs or at family request. Results: Of 94 infants, 38 [40%; 19 females (50%), mean age at diagnosis 0.3±0.4 years] were managed with INT (14 LQT1 (36%), 15 LQT2 (39%), 8 LQT3 (21%)). Genetic testing and ECG screening were performed because of a family history in all 38 infants including 11 (29%) with a family history of SCA/SCD. None had fetal bradycardia reported or any cardiac symptoms prior to diagnosis. Mean neonatal QTc during the first week of life was 477±41ms and 442±6ms at 3 months of age. No cardiac events were reported during a mean follow-up of 3.9±2.3 years. Management was escalated from INT to prophylactic pharmacologic therapy in 8 infants (21%) with nadolol in 4, propranolol in 3, and LQT3 mutation-specific therapy with flecainide in 1 based on 2 consecutive QTc values>470ms, at a mean age of 4.3±2 years (mean QTc at treatment initiation 485±13ms). Conclusions: In selected LQTS infants with favorable down-trending QT and access to close follow-up, INT rather than universal prophylactic drug therapy can be considered. This approach may offer an alternative strategy in infancy, avoiding unnecessary early exposure to medication-related side effects and reinforcing individualized genotype- and phenotype-directed tailoring of therapeutic options.

Background: Heart failure (HF) is the leading cause of mortality in adults with congenital heart disease (CHD) after transcatheter pulmonary valve replacement (TPVR), likely due to preexisting myocardial dysfunction and suboptimal reverse remodeling. Left ventricular (LV) diastolic dysfunction, unmasked by an acute increase in preload post-TPVR, may elevate left-sided filling pressures and precipitate pulmonary edema. However, the prognostic implications of elevated left-sided filling pressures prior to TPVR are currently unknown. Objective: To evaluate the prognostic value of pre-TPVR pulmonary artery wedge pressure (PAWP) and the heart failure with preserved ejection fraction – Age, Body mass index (BMI), Atrial fibrillation (HFpEF-ABA) score in patients undergoing TPVR. Methods: Adults with congenital heart disease (CHD) undergoing TPVR were stratified by pre-implant PAWP (<15 vs ≥15 mmHg) and HFpEF-ABA score (low <25%, intermediate 25–75%, high >75%). The composite endpoint was all-cause mortality, heart transplantation, heart failure (HF) hospitalization, or sustained ventricular arrhythmia. Kaplan-Meier and Cox regression analyses assessed associations with clinical outcomes. Results: Out of 150 patients, 37 (24.7%) had PAWP ≥15 mmHg. Elevated PAWP was associated with older age (36 [31;53] vs. 26 [19; 37] years, p<0.01), BMI (27.9 [24.5; 35.1] vs. 24.2 [20.6; 29.7] kg/m 2 , p<0.01), and higher HFpEF-ABA score (42.8 [9.5;63.6] vs. 6.4 [2.5;18.1]%, p<0.001) compared to normal PAWP. Over a median follow-up of 38 [13; 83] months, 26 events (17.3%) occurred. Kaplan-Meier analysis demonstrated a significant difference in event-free survival based on pre-TPVR PAWP categories (log-rank p=0.002) and HFpEF-ABA score categories (log-rank p<0.001). Elevated PAWP was associated with adverse outcomes (hazard ratio [HR] 4.27, 95% CI 1.61–11.31, p=0.003) (Figure 1), but this was no longer significant after age adjustment. HFpEF-ABA ≥25% was associated with adverse outcomes (HR 10.6, 95% CI 3.8–30.0, p<0.001) (Figure 2), independent of N-terminal prohormone of brain natriuretic peptide levels and left ventricular ejection fraction. Conclusion: Albeit confounded by demographics, pre-TPVR PAWP correlated with adverse long-term outcomes, and patients with this hemodynamic profile may require closer post-procedural surveillance. HFpEF-ABA was independently associated with incident events, representing an inexpensive, novel prognostic tool in patients undergoing TPVR.

Introduction: Blood pressure (BP) is a complex physiological marker. Cuffless devices, often based on photoplethysmography (PPG), enable frequent or continuous BP monitoring without arterial occlusion, enhancing comfort and usability in both inpatient and outpatient settings. Various devices have received regulatory clearance, but they are not yet included in clinical guidelines due to evolving validation standards. Aim: To evaluate accuracy of the Biobeat WP613 device for continuous BP monitoring using invasive intra-arterial pressure (IAP) monitoring in ICCU patients. Methods: This prospective, single-center study enrolled adults undergoing cardiac surgery at Chaim Sheba Medical Center (June 2020–January 2023) who had radial artery catheters for standard BP monitoring. Severe shock patients were excluded. Demographics and Fitzpatrick skin tone were recorded. ClinicalTrials.gov NCT04071015. Post-op, patients were simultaneously monitored with the standard IAP system and the Biobeat device. Continuous BP and HR were collected for up to five days. Data analyzed post hoc. Tested device The WP613 (Biobeat, Israel) is FDA-cleared, chest-worn, PPG-based device that uses multi-wavelength light and a sensor to monitor vital signs. It wirelessly transmits data to a cloud based algorithms to measure BP, cardiac output, stroke volume, and more. It also records a single-lead ECG and has a 5-day battery life. Results: A total of 96 patients were enrolled, with 88 included in the final BP analysis after excluding 8 due to technical issues. Of those, 80 received inotropic support. The average age was 63.2±12.2 years, with 33% female. Monitoring lasted an average of 25.6±17.2 hours, yielding over 78000 readings for each BP parameter and over 92000 HR readings (Fig 1) . Patients represented the full range of skin tones, classified using the Fitzpatrick scale I–VI. The Biobeat device showed excellent correlation with IAP monitoring: r=0.959 for SBP, 0.973 DBP, and 0.962 HR. Bland-Altman showed minimal bias (e.g., 0.1±4.8 for SBP) (Fig 2) . Correlation remained strong across BP ranges and skin tones. Heatmaps and representative cases confirmed close tracking between Biobeat and IAP (Fig 3) . Conclusion: The tested cuffless device (Biobeat) offers a high level of accuracy and agreement for BP and HR compared to data obtained by IAP monitoring in post-cardiac surgery patients. Further studies are needed to validate these findings in various populations and clinical settings.

Background: Effective risk factor modification, including management of obesity and diabetes mellitus (DM), is essential to mitigating cardiovascular complications after hematopoietic stem cell transplantation (HSCT). Given the growing use of GLP-1 receptor agonists (GLP-1 RAs), large-scale studies are needed to assess their cardiovascular impact in patients undergoing HSCT. Methods: Using the TriNetX network, we identified patients who underwent HSCT and had DM or obesity. Patients were categorized into two cohorts: those who received GLP-1 RAs and those who did not. Outcomes, including all-cause mortality, all-cause hospitalization, acute myocardial infarction (AMI), atrial fibrillation (AF), cerebrovascular accident (CVA), and heart failure (HF) exacerbation, were assessed at 1 year, 3 years, and 5 years follow-up. Cohorts were propensity score-matched based on medical comorbidities, transplant diagnoses, and conditioning regimens. Results: Of the initial 17,475 patients with HSCT and DM/obesity, 876 (5.0%, 46.0% females, mean age 58.4 +/- 11.3 years old) received GLP-1 RA and 16,599 (95.0%, 40.8% females, mean age 55.6 +/- 14.3 years old) did not. After propensity score matching, 873 patients were divided equally into each cohort (Table). GLP-1 RA was associated with lower odds of all-cause mortality (1-year: odds ratio [OR]: 0.53; 95% confidence interval [CI]: 0.38–0.76; p<0.01; 3-year: OR: 0.52; CI: 0.40–0.69; p<0.01; 5-year: OR: 0.44; CI: 0.33–0.58; p<0.01), all-cause hospitalization (1-year: OR: 0.74; CI: 0.61–0.89; p<0.01; 3-year: OR: 0.66; CI: 0.55–0.79; p<0.01; 5-year: OR: 0.72; CI: 0.59–0.87; p<0.01), and HF exacerbation (1-year: OR: 0.65; CI: 0.44–0.96; p=0.03; 3-year: OR: 0.59; CI: 0.43–0.81; p<0.01; 5-year: OR: 0.53; CI: 0.38–0.74; p<0.01), compared to the non–GLP-1 RA group. At 5-year follow-up, GLP-1 RA use was also associated with lower odds of AF (OR: 0.71; CI: 0.53–0.94; p=0.02). No significant differences were noted in AMI or CVA at 1-, 3-, and 5-years of follow-up. Conclusion: After propensity score-matching in this retrospective cohort study, GLP-1 RA use was associated with significantly lower odds of all-cause mortality, all-cause hospitalization, and heart failure exacerbation at 1-, 3-, and 5-year of follow-up in patients with DM/obesity who underwent HSCT. At 5 years, use of GLP-1 RA was associated with lower odds of AF.

Background: Left atrial (LA) strain is a marker of atrial myopathy and remodeling. While echocardiographic LA strain is increasingly used to assess atrial function, the prognostic value of change in LA strain before and after catheter ablation (CA) for atrial fibrillation (AF) remains underexplored. Objective: To evaluate the association between quartiles of LA strain parameters—including pre-ablation strain, post-ablation strain, and change in strain—with atrial fibrillation recurrence, stratified by ejection fraction (EF). Methods: This retrospective study encompassed AF patients who underwent their first CA at Mayo Clinic Arizona from Oct 2018 to Feb 2022. Transthoracic echocardiography parameters, including the three LA strain (LAS) phases—contraction, conduit, and reservoir—were collected using TOMTEC software on the closest date before the CA procedure. Logistic regression analysis was used to evaluate the association between LAS parameters and AF recurrence post-CA, adjusted for clinical covariates including age, gender, hypertension, diabetes, coronary artery disease, dyslipidemia, obstructive sleep apnea, thromboembolism, TIA/stroke, chronic kidney disease, and AF type. Results: Out of 335 patients who underwent CA, 222 had both pre- and post-ablation LA strain data. Among these, 71 of 222 patients (31.98%) experienced AF recurrence after CA. The mean age at time of procedure was 66.9 ± 10.3 years; 150 (67.57%) were male, and 83 (37.39%) had persistent AF. Significant associations were observed between specific quartiles of LA strain and AF recurrence. In patients with EF >50%, Q4 of contraction strain change (pre- vs. post-ablation) was strongly associated with increased recurrence risk (OR 8.80; 95% CI 1.80–42.98). Similarly, post-ablation contraction strain Q4 was associated with higher recurrence in both the overall group (OR 6.36; 95% CI 1.47–27.53) and the EF>50% subgroup (OR 8.80; 95% CI 1.80–42.98). In contrast, reservoir strain change Q2 (OR 0.10; 95% CI 0.01–0.86), and post-ablation reservoir strain Q3 (OR 0.09; 95% CI 0.01–0.69) and Q4 (OR 0.10; 95% CI 0.02–0.70) were protective. Conclusions: Greater increases in contraction strain post-ablation and higher post-ablation contraction strain were strongly associated with AF recurrence, particularly in those with preserved EF. Conversely, favorable reservoir strain post-ablation was protective. LA strain may offer key prognostic value in risk-stratifying AF patients undergoing ablation.

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.