Citations

Introduction: Artificial intelligence (AI) and wider digital technologies are accelerating healthcare systems’ attempts to address the financial and moral imperatives of improving health disparities and thus wider population health outcomes. Yet adoption has thus far been slower in less common conditions including carcinoid, its syndrome, and related heart disease especially amid wider system shocks like the COVID-19 pandemic and its lingering effects. This is the first known AI-augmented nationally representative analysis of mortality and disparities for these associations. Methods: Quantum BAyesian Machine learning-augmented Propensity Score translational (QBAM-PS) statistics with multivariable regression was performed on the largest all payor US inpatient dataset, the National Inpatient Sample. Results: Of the 208,257,049 adult hospitalizations from 2016-2022, 124,954 (0.06%) had carcinoid tumors. Of the 71,402 hospitalizations with carcinoid from 2016-2019, 26,711 (37.41%) had metastases, 2,835 (3.97%) had acute heart failure, and 2,042 (2.86%) died. But of the 53,552 hospitalizations with carcinoid from 2020-2022, diagnosed metastases (38.04%) had increased, as did acute heart failure (4.21%) and mortality (3.73%), while 0.04% had diagnosed COVID. In all adult hospitalizations from 2016-2019 by QBAM-PS multivariable regression controlling for clinical confounders and severity, carcinoid and carcinoid syndrome did not significantly increase mortality, but carcinoid was significantly less likely to be diagnosed among Hispanics (OR 0.73) and Asians (OR 0.46) compared to Caucasians, in addition to Medicare (OR 0.71) and VA (OR 0.65) compared to private insurance, and more likely to be diagnosed in the highest versus lowest income quartile (OR 0.124) (all p<0.001). By 2020-2022, carcinoid and its syndrome did not significantly increase the odds of COVID diagnosis. But again carcinoid was significantly less likely to be diagnosed in Hispanics (OR 0.68), Asians (OR 0.61), Medicare (OR 0.78), and VA (OR 0.59), while the highest income again increased diagnosis odds (OR 1.19) (all p<0.01). There were no mortality disparities within carcinoid during either time period. Conclusions: This large multi-year analysis supports improvements in metastatic carcinoid detection and heart disease management, including through the COVID pandemic, though amid persistent racial, insurance, and income disparities.

Background/Objective: Hypertension is the most prevalent chronic disease in primary care and a leading cause of cardiovascular morbidity and mortality. Despite existing guidelines, therapeutic inertia and suboptimal control persist. Large language models (LLMs) offer a potential valuable addition to augment clinical decision-making, yet their reliability for guideline-driven tasks remains unverified. This study evaluated the accuracy and safety of hypertension management recommendations generated by three LLMs compared to expert responses. Methods: Fifty-one clinical vignettes representing 17 core hypertension management concepts were constructed by hypertension experts. Each case was submitted to three LLMs (GPT-4, Gemini, MedLM) and a hypertension expert also wrote the “gold standard” answers. Three blinded expert reviewers rated each response on a 4-point accuracy scale, a binary safety (safe/unsafe) scale, and attempted to identify the source (LLM vs. expert) providing the response. Ratings were analyzed using mean scores, percentages of accurate and safe responses, and inter-rater agreement. 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 three LLMs (Gemini 35%, MedLM 14%), but remains lower than experts’ responses (68%). Evaluators misidentified LLM responses as expert-written in 10 to 25% of cases, particularly with GPT-4. Inter-rater reliability for accuracy ratings was highest for expert-generated responses (ICC 0.81), with progressively lower agreement for GPT-4 (0.76), Gemini (0.70), and MedLM (0.68). A similar pattern was observed for safety and source discrimination ratings. The agreement was strongest for safety assessments and weakest for source discrimination. Conclusion: Among three tested LLMs, GPT-4 demonstrated closer agreement to expert decisions thereby showing greater potential for supporting hypertension management. However, current LLMs’ versions frequently produce inaccurate or unsafe recommendations and remain inferior to expert judgment. Human-in-the-loop supervision remains essential when deploying LLMs for clinical decision-making.

Introduction: The use of intravascular ultrasound (IVUS) to guide lower extremity deep venous stent placement is associated with improved identification of the degree of maximal vessel stenosis, vessel obstruction, and thrombus burden, compared to venography alone. As the US medical system moves towards value-based care, the financial impact of interventional tools requires close consideration. Currently, there are limited evaluations of the cost effectiveness of IVUS during venous procedures. Research Question: This study seeks to examine the cost-effectiveness of IVUS in lower extremity deep venous interventions. Methods: Medicare fee-for-service claims data from 2016 through 2021 for beneficiaries aged ≥ 65 years undergoing lower extremity venous interventions with stent placement, thrombolysis, and/or thrombectomy were analyzed. Cost ratios between IVUS-guided and non-IVUS-guided procedures were assessed using gamma regression, adjusting for demographic and clinical variables. Results: A total of 52,610 patients were included, with 42.6% undergoing IVUS-guided procedures. IVUS utilization varied by setting, with higher usage in hospital-based outpatient centers (75.3%) and ambulatory surgical centers/outpatient-based laboratories (ASC/OBL; 86.4%) compared to inpatient hospitalizations (10.4%). Among inpatient procedures, IVUS-guided venous intervention was associated with greater cost than non-IVUS procedures at 90 days, with an adjusted cost ratio of 1.04 (95% CI 1.01-1.07), yet was associated with an average 0.6-day shorter hospitalization (p < 0.001; Figure 1, Figure 2 ). There were marginal increased costs associated with use of IVUS in inpatient procedures persisting through one- and three-years follow-up, with adjusted cost ratios of 1.05 (95% CI 1.02-1.08) and 1.05 (95% CI 1.02-1.09), respectively. In contrast, IVUS use was associated with significant cost savings in outpatient settings, with adjusted cost ratios of 0.71 (95% CI 0.69-0.73) in hospital-based outpatient settings and 0.75 (95% CI 0.73-0.78) in ASC/OBL at 90 days. These cost savings persisted at one- and three-year follow-up. Conclusions: IVUS-guided venous intervention was associated with cost savings in outpatient and ASC/OBL settings, while maintaining near cost equivalence in inpatient settings. These findings suggest that in addition to the clinical benefit of IVUS for venous intervention, IVUS is a cost-effective strategy, particularly in the outpatient setting.

Background: Atrial fibrillation (AF) significantly impacts quality of life (QoL) and is often observed in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Acoramidis achieves near-complete (≥90%) transthyretin (TTR) stabilization and is approved in the USA, the UK, Europe and Japan for the treatment of ATTR-CM in adults. In the phase 3 ATTRibute-CM study (NCT03860935), acoramidis treatment significantly reduced the time to all-cause mortality (ACM) or first cardiovascular-related hospitalization (CVH) at Month 30, and resulted in improved 6-minute walk distance (6MWD), Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) scores and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels relative to placebo. The clinical efficacy of acoramidis has not yet been reported in patients with ATTR-CM and with an AF or atrial flutter (AFL) diagnosis at baseline. Research Question: How does acoramidis treatment affect ACM or first CVH, 6MWD, KCCQ-OS scores, and NT-proBNP levels at Month 30 in participants with ATTR-CM with or without AF/AFL diagnosis at baseline? Methods: The ATTRibute-CM study design has been previously published. This post hoc analysis included participants in the modified intention-to-treat population (N=611) grouped by AF/AFL diagnosis at baseline (defined as recorded AF medical history or the presence of AF or AFL on an ECG at enrollment). The rate of ACM or first CVH at Month 30 was compared between groups using a stratified Cox proportional hazards model. Changes from baseline to Month 30 in 6MWD, KCCQ-OS scores and NT-proBNP levels were summarized descriptively. Results: Overall, 62.8% (384/611) of participants had an AF/AFL diagnosis at baseline (acoramidis: 255/409, placebo: 129/202). These participants had lower mean 6MWD and KCCQ-OS scores and higher median NT-proBNP levels than those without AF/AFL diagnosis at baseline. Treatment with acoramidis reduced ACM or first CVH, slowed the decline in 6MWD and KCCQ-OS scores and blunted the rise in NT-proBNP compared with placebo, regardless of AF/AFL diagnosis at baseline ( Table ). Conclusions: Acoramidis improved clinical outcomes (ACM, CVH), functional status, QoL and NT-proBNP levels relative to placebo in participants with ATTR-CM, regardless of AF/AFL diagnosis at baseline.

Background: Cuffless blood pressure (BP) monitoring devices with the ability to continuously and noninvasively collect data could transform the screening and management of hypertension. While some wearable devices can estimate BP, their accuracy and reliability remain limited. Objective: To evaluate the feasibility of using a wrist-worn photoplethysmography (PPG) device (Lifeleaf®) in combination with a supervised learning algorithm to infer clinically useful BP measurements. Methods: A total of 87 patients undergoing electrophysiology procedures were enrolled (Table 1). Time-synchronized BP data from an intra-arterial line served as the reference. These data were divided into (1) a training set to develop a convolutional neural network (CNN) and (2) a testing set to assess the algorithm’s predictive performance. Data from 60 patients were used to train the model, and the remaining 27 patients were used for validation. Results: Data from 81 of 87 patients were included in the final analysis. The mean age was 63.6 ± 10.5 years, and 69.1% were male. A total of 6,977 paired PPG and arterial BP readings were analyzed. The mean absolute deviation for systolic BP was 13.08 ± 17.22 mm Hg, and for diastolic BP, 8.42 ± 10.56 mm Hg. Subgroup analysis revealed reduced correlation in patients with BP >140/90 mm Hg, likely due to fewer training samples in this range. Conclusion: This study demonstrates the feasibility of extracting clinically meaningful BP measurements from a PPG device using a supervised learning algorithm. The use of arterial line BP as the reference standard adds methodological rigor. Future work will focus on enhancing model performance, particularly in the hypertensive cohort.

Background: The purpose of this study was to describe outcomes after heart transplantation in adults with congenital heart disease (CHD) based on the experience from a high volume transplant center. Method: Retrospective cohort study of adults with CHD who underwent heart transplantation at Mayo Clinic Rochester, MN (2003-2024). Results: Of 89 patients (age 40 [9;66], 52% males) who underwent heart transplantation, 67 (75%) had biventricular physiology while 22 (25%) had Fontan physiology. Fifty (56%) and 39 (44%) receives single organ versus multi-organ transplantation, respectively. The proportion of patients with Fontan palliation undergoing heart transplantation was higher in the late (after 12/31/2023) era 31% [21 /67] versus 5% [1/22], p=0.005.The 30-day, 1-year, and 5-year survival rates were 97%, 91%, and 87%, respectively, and these rates were higher than the estimates from national registries. Patients with Fontan physiology had lower post-transplant survival compared to biventricular physiology, but Fontan physiology was not an independent predictor of mortality. The predictors of post-transplant mortality were longer cardiopulmonary bypass time, mechanical ventilation duration and postoperative mechanical circulatory support. Conclusions: We observed a higher post-transplant survival compared to historical estimates. Post-transplant mortality was related to operative and postoperative factors, and not to CHD physiology. There was a high proportion of patients requiring multi-organ transplantation, and a rising proportion of patients with Fontan physiology who underwent transplant in the later part of the study. These findings highlight important demographic changes, importance of institutional expertise, and the need for improvements in risk stratification and referral patterns to align with these changes.

Background: Coronary artery (CA) injury from catheter ablation is an uncommon complication, but the risk is under recognized. In pediatrics, CA imaging to assess for CA proximity is not commonly performed prior to ablation. The risk for CA injury significantly increases when a CA is within 3 mm of the site of ablation. Research Question: How often is there a CA within 3 mm of a potential ablation site in pediatric patients? Methods: A retrospective review of all coronary computed tomography angiograms (CTAs) in pediatric patients <18 years of age at Mayo Clinic from 2017 through 2023 was conducted. The proximity of CAs to potential ablation sites in the coronary sinus and the appendage bases were measured. Results: Seventy-two CTAs in 67 patients >15 kg and <18 years old were included. Median age was 12 years and median weight was 41 kg. In right dominant CA circulation, 23/36 (64%) had a CA within 3 mm of the coronary sinus. For those within 3 mm, the mean distance from the coronary sinus was 1.4 mm +/- 0.2 mm for a length of 10 mm +/- 2 mm (Figure 1A). In left and co-dominant CA circulation, 26/26 (100%) had a CA within 3 mm of the coronary sinus with a mean distance of 1.1 mm +/- 0.2 mm for a length of 27 mm +/- 2 mm (Figure 1B). The right CA was within 3 mm of the appendage base in 49/69 (71%). For those within 3 mm, the mean distance was 1.9 mm +/- 0.2 mm for a length of 17 mm +/- 2 mm. The circumflex CA was within 3 mm of the appendage base in 50/68 (74%). Of the 50 within 3 mm, the mean distance was 2.1 mm +/- 0.2 mm for a length of 9 mm +/- 2 mm. Conclusion: Most pediatric patients have a CA ≤ 3 mm from potential ablation sites in the coronary sinus and base of the appendages. Before performing catheter ablation in these areas, precautions should be taken to avoid CA damage.

Background: Cardiac arrest is a major global health concern, contributing significantly to mortality rates. While conventional cardiopulmonary resuscitation (CPR) has long been the standard care approach, emerging research indicates that extracorporeal cardiopulmonary resuscitation (ECPR) may provide superior survival advantages. Studies suggest that timely application of ECPR can lead to improved outcomes, particularly in terms of survival rates and neurological recovery. The comparative efficacy of ECPR is further corroborated by various randomized controlled trials (RCTs), as well as retrospective and prospective studies. Search Methods: We conducted a comprehensive search of databases including PubMed, Google Scholar, Cochrane Library, PLOS One, ClinicalTrials.gov, and ScienceDirect from 2014 to 2025. Our analysis included 3 RCTs, 3 prospective, and 5 retrospective studies (n=154,216). Inclusion criteria involved patients undergoing cardiac arrest managed in inpatient or outpatient settings. Meta-analysis was performed using Review Manager (RevMan) version 5.4, calculating safety endpoints as odds ratios for ROSC, favorable neurological outcomes , and survival rates. Results: Findings indicated that ECPR was associated with a significantly higher rates of ROSC (OR 0.36, 95% CI [0.24–0.54], p<0.00001) and favorable neurological outcome (OR 0.47 , 95% CI [0.37–0.60], p<0.00001). The Survival at 6 months was significantly better in the ECPR group (OR 0.21, 95% CI [0.12–0.36], p<0.00001). Although CCPR showed higher odds for survival to ICU (OR 1.31, 95% CI [0.86–2.00], p=0.21) and discharge (OR 1.42, 95% CI [0.90–2.25], p=0.13), these did not reach statistical significance. Conclusion: ECPR shows improved ROSC and neurological outcomes over conventional CPR, with higher six-month survival rates, emphasizing the need to adopt ECPR in cardiac arrest management.

Background: Cardiac disease is the leading cause of premature mortality in Friedreich Ataxia (FA). However, validated prognostic indicators or early imaging biomarkers that can reliably predict cardiac events are lacking. To address this gap, we created a multicenter FA cardiac registry to characterize disease progression and identify early echocardiographic (echo) predictors of major adverse cardiac events (MACE). Methods: FA subjects from 6 North American centers with at least two echos performed ≥5 years apart were included. Demographics, FA-specific disease characteristics, and MACE (a composite of death, heart failure hospitalization, aborted sudden cardiac death, and/or life-threatening arrhythmia) were abstracted. Digital echo images were re-read at a centralized core lab. Paired T tests were utilized for comparison of the normally distributed first and second echo parameters, and logistic regression models were utilized to evaluate for predictors of MACE. Results: Of 115 subjects, 52 (45%) were female. Mean age at diagnosis was 10 ± 3 years, median GAA1 repeat length (a marker of genetic severity) was 700 (range 66–1200), and median age at first analyzed echo was 12 years (range 4-36). MACE occurred in 35 (30%) of the cohort. Serial echocardiograms demonstrated progressive worsening of multiple cardiac parameters over time, including markers of ventricular thickness and hypertrophy, chamber size, systolic function, and novel markers of atrial and ventricular strain (Table 1). On univariate analysis, several markers of hypertrophy and systolic function from the earliest analyzed echo predicted MACE. However, after adjusting for age of diagnosis, GAA1 repeat length, and collinearity among variables, only posterior wall thickness in diastole (PWTd) remained an independent predictor of MACE (odds ratio 1.8 per mm increase, 95% CI 1.1–3.3, p = 0.028). Conclusions: This multicenter FA registry identifies early posterior wall thickness as a significant and independent predictor of major adverse cardiac events in FA. Each millimeter increase in PWTd on early echo is associated with nearly double the odds of MACE. This commonly acquired parameter is often overlooked and may serve as a powerful early marker of cardiac risk. Further investigation of PWTd as a potential surrogate endpoint for therapeutic trials in FA is warranted.

Background: Adults with congenital heart disease (CHD) face ongoing physical, emotional, and psychosocial challenges that impact long-term outcomes. Research is limited on how their health topic interests vary by levels of empowerment. The 15-item Gothenburg Empowerment Scale (GES) assesses CHD patient empowerment across five domains. Objective: Examine the association between patient empowerment levels and patient-prioritized health education topics among adults with CHD. Methods: This cross-sectional study included adults (≥18) with self-reported CHD enrolled in the Empower My Congenital Heart digital study. Participants completed the GES survey and responded to open-ended questions regarding information of interest to them in managing their healthcare. GES scores were divided into tertiles, and responses were grouped into patient-prioritized topics. Descriptive analysis examined associations between empowerment levels and topic preferences. Results: Of 292 eligible patients, mean age was 45.6 ± 14.7 years, 91.4% were Caucasian, and 66.4% were female. The median (25th, 75th) GES score was 62 (57, 68). The most frequently observed patient prioritized topic was CHD health knowledge (73%), followed by interest in building CHD community (52.7%), lifestyle management (23.6%), health care navigation (7.2%), research and representation (5.1%). Participants in the lower and middle GES tertiles more frequently expressed interest in foundational sub-topics such as understanding CHD and surgical history, finding ACHD specialists, exercise and nutrition. In contrast, participants in the highest GES tertile prioritized sub-topics related to aging with CHD, managing menopause, CHD research and legislative activities. Peer support was a common topic across all groups (Figure 1). Patient quotes were stratified by tertile and patient prioritized health topics and subtopics as summarized in table 1. Conclusion: Adults with CHD prioritized varied health education topics depending on their baseline empowerment levels. Those with lower GES scores prioritized foundational information and guidance, while those with higher scores prioritized community-oriented and research-related topics. These findings could help tailor CHD patient-centered education strategies based on individual empowerment profiles.