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Background: Coronary microvascular dysfunction (CMD) is a common cause of angina with non-obstructive coronary arteries (ANOCA), but its role in patients with a history of myocardial infarction with non-obstructive coronary arteries (MINOCA) is much less understood. We investigated the incidence of major adverse cardiac and cerebrovascular events (MACCE) in patients undergoing invasive assessment for CMD, divided into patients with MINOCA versus patients with ANOCA. We hypothesized that CMD would be common in both groups. Methods: Serial patients undergoing invasive coronary provocation testing between 2012 and 2022 were divided into MINOCA (n=76) or ANOCA (n=561). Doppler study was performed in the left anterior descending artery. CMD was defined as either coronary flow reserve (CFR) <2.5 with adenosine or <50% increase in flow with acetylcholine. Patients were followed prospectively through 2025. Incidence of MACCE (cardiac death, non-fatal MI, hospitalization for heart failure, urgent revascularization, and stroke) was compared between MINOCA and ANOCA and further analyzed by CMD status. Kaplan-Meier curves were constructed and Cox proportional hazards models were used to estimate hazard ratios (HRs). Results: Among patients with MINOCA, 53 of 76 (70%) had CMD, compared to 363 of 561 (65%) with ANOCA. Invasive provocation testing was performed a median of 163 days (IQR 13 – 255 days) after the MI in the MINOCA group. Patients were then followed for a median of 4.4 years (IQR 3.0 – 6.9 years). MACCE-free survival was significantly lower in patients with MINOCA compared to those with ANOCA (HR = 3.57, p < 0.001; Figure 1). The major contributor to MACCE was non-fatal MI in MINOCA (24%) and heart failure hospitalization in ANOCA (6%). The presence of CMD was associated with worse prognosis in both MINOCA (HR = 3.76, p = 0.02) and ANOCA (HR = 8.35, p < 0.001; Figure 2). Conclusions: Patients with MINOCA experience significantly higher long-term risk of major adverse events compared to those with ANOCA. CMD is common in both groups and is independently associated with worse outcomes. Specifically, patients with CMD had higher rates of MACCE over time, regardless of whether they presented with MINOCA or ANOCA. Invasive assessment of CMD in patients with myocardial infarction and non-obstructive coronary arteries may improve risk stratification and inform management strategies in these understudied populations

Introduction: Diabetes affected 529 million people globally by 2021, largely due to rising obesity contributing to Type 2 diabetes (DM2). In the U.S., it is the seventh leading cause of death and closely linked to cardiovascular disease, the leading cause of mortality in this population. Effective, low-cost strategies to improve glycemic and cardiometabolic health are essential. Psyllium, a viscous soluble fiber, has been shown to lower LDL cholesterol and improve glycemic indices, whereas non-viscous fibers like wheat dextrin lack similar benefits. Emerging lipid markers such as ceramides are associated with cardiometabolic risk but have not been studied in response to fiber. The interaction between fiber and GLP-1 agonists is also unclear. Hypothesis: Psyllium supplementation will improve cardiometabolic markers more than wheat dextrin in people with DM2. Methods: In this randomized trial at Mayo Clinic, adults with DM2 (HbA1c 6.5–10%) were randomized to psyllium or wheat dextrin for 12 weeks. Participants were recruited via electronic health records. Key exclusions: GI disease, bariatric surgery, steroid use, and pregnancy. Follow-up visits occurred at weeks 4, 8, and 12. Primary endpoints were changes in HbA1c and fasting glucose; secondary endpoints included lipids, ceramides, hsCRP, and BMI. An ex post facto analysis evaluated GLP-1 use. Primary analysis was intention-to-treat. Adherence = ≥85% dose completion. Results: Ninety-eight participants enrolled (Psyllium n=50, Dextrin n=48) with similar baseline characteristics. At 12 weeks, psyllium significantly reduced HbA1c (-0.38 ± 0.69, p=0.002). Among adherent users, HbA1c dropped further (-0.41 ± 0.70, p=0.001) with reduced fasting glucose (-14.5 ± 38.2, p=0.013). Wheat dextrin showed no benefit. In subgroup analysis, GLP-1 users on psyllium saw greater HbA1c reductions than non-users (-0.45 vs. -0.23), while GLP-1 users on dextrin had no change (+0.06). No significant changes were found in ceramides, lipids, or BMI in any analysis. CRP trended lower in adherent psyllium users (p=0.055). Conclusion: Psyllium significantly reduced HbA1c over 12 weeks in DM2, especially in adherent and GLP-1–treated groups. Effects may be attributed to psyllium's ability to form a gel in the gastrointestinal tract, modulating nutrient absorption. No effects were seen on ceramides or lipids, likely due to low baseline levels in the latter. Psyllium appears to be a safe, accessible adjunct for glycemic control in DM2.

Case Description: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are associated with immune-related adverse events, including cardiovascular toxicity. While ICI-myocarditis is rare but potentially fatal, thrombotic complications—such as venous thromboembolism, arterial occlusion, and non-bacterial thrombotic endocarditis (NBTE)—are underrecognized. These raise questions about the roles of malignancy-associated hypercoagulability versus ICI-induced effects. We present a case of NBTE and myocardial microthrombi mimicking ICI-myocarditis. A 76-year-old woman with metastatic adenosquamous lung cancer and recent DVT (on apixaban and aspirin) presented with worsening dyspnea three weeks after starting pembrolizumab (Image 1). One week earlier, CT pulmonary angiography and coronary angiography were unrevealing. On presentation, she was stable but had peripheral edema, a late diastolic murmur, and elevated hs troponin (706→657→656 ng/L). NT-proBNP was 11,500 pg/mL. Cardiac MRI showed mid-wall late gadolinium enhancement (LGE), myocardial edema, and elevated T2 values—findings concerning for ICI-myocarditis. She initially improved on intravenous methylprednisolone. A week later, brain MRI showed multifocal embolic infarcts. Doppler ultrasound revealed a new left-sided DVT. TEE showed no intracardiac thrombus but identified a thickened aortic valve with moderate-to-severe regurgitation, a thickened mitral A2 segment with moderate regurgitation, and a patent foramen ovale (PFO) with left-to-right shunting. Findings raised concern for NBTE with systemic embolism or paradoxical embolism. Anticoagulation was transitioned to heparin, then warfarin. She was discharged on oral prednisone without further cancer therapy. Two months later, she died suddenly. Autopsy revealed fibrin-rich vegetations on the mitral valve consistent with NBTE and thromboembolic infarcts in small myocardial arteries, without inflammatory infiltrates or myocardial scarring (Image 2 and 3). Conclusion: This case highlights NBTE and microthrombi as important mimics of ICI-myocarditis. Despite MRI features suggestive of inflammation, pathology confirmed ischemic injury. ICIs have been suggested to promote thrombosis through elevated factor VIII, von Willebrand factor, reduced protein S, and systemic inflammation. Clinicians should consider thrombotic mimics in ICI-treated patients with cardiac symptoms and abnormal imaging. Tissue diagnosis may be necessary to guide management.

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.