Citations

Coronary artery disease (CAD) remains a leading cause of global morbidity and mortality. Accurate diagnosis of ischemia-causing coronary stenoses is essential for guiding revascularization and improving outcomes. Although invasive fractional flow reserve (FFR) remains the gold standard for functional lesion assessment, its use is limited by procedural invasiveness, cost, and complexity. CT-derived FFR (FFRct), based on computational fluid dynamics (CFD), was the first major advance in noninvasive physiological assessment, but its adoption has been hindered by intensive off-site computation and dependence on high-quality imaging. This review summarizes the evolution from invasive FFR to AI-driven functional assessment of coronary lesions. We examine the principles and validation of CFD-based FFRct and then focus on the shift toward artificial intelligence, including both machine learning (ML) and deep learning (DL) approaches. These methods range from models using engineered geometric and plaque features trained on large synthetic datasets to end-to-end systems that learn directly from imaging data. We discuss key validation studies evaluating diagnostic accuracy, prognostic value, and clinical utility, with attention to performance in challenging settings such as intermediate stenoses, heavy calcification, and patients with comorbidities. We also highlight major barriers to widespread adoption, including dependence on input data quality, limited explainability, regulatory hurdles, and integration into clinical workflows. Finally, we outline future directions, including AI-enabled virtual PCI planning, multimodal risk stratification, and broader access to functional cardiac assessment. AI has the potential to transform noninvasive coronary imaging by enabling a single CCTA scan to provide rapid, integrated evaluation of anatomy, plaque characteristics, and physiological significance, supporting more personalized care and better clinical outcomes.

Background/Objectives: Thoracic aortic aneurysm (TAA) often results from structural degeneration of the aortic wall. Traditional management focuses on hemodynamic control using beta-blockers (BB) and angiotensin receptor blockers (ARBs). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), originally developed for diabetes and weight management, may offer additional vascular protective benefits through anti-inflammatory, antioxidative, and matrix-stabilizing mechanisms. However, their role in reducing mortality and thoracic aortic dissection (TAD) risk in patients with TAA has not been evaluated in human populations. In this study, we aimed to assess the association between GLP-1 RA use and the risks of mortality and thoracic aortic dissection. Methods: We conducted a retrospective cohort study of adults diagnosed with TAA between 2018 and 2024 across three Mayo Clinic sites. Patients receiving GLP-1 RAs were compared with non-users using 1:1 propensity score matching. Outcomes included all-cause mortality, cardiovascular mortality, and incident TAD. Kaplan–Meier and Cox proportional hazards analyses were performed. Results: A total of 32,279 patients with TAA, with a median age of 68.0 [IQR: 59.0–76.0] and 70.7% male, were included in a 1:1 propensity score match. This yielded a balanced cohort of 588 GLP-1 RA users and 588 non-users. Through a median follow-up of 4.1 (2.2, 5.9) years, GLP-1 RA use was associated with significantly lower 5-year cumulative incidence of all-cause mortality (5.0% vs. 14.5%, HR: 0.31; 95% CI: 0.19–0.50; p < 0.001), cardiovascular mortality (1.9% vs. 5.5%, HR: 0.30; 95% CI: 0.13–0.70; p = 0.005), and TAD (0.9% vs. 4.0%, HR: 0.19; 95% CI: 0.06–0.60; p < 0.0004). Conclusions: GLP-1 RAs are associated with reduced incidence of all-cause mortality, cardiovascular mortality, and TAD incidence in patients with TAA. Prospective studies are needed to confirm these findings and evaluate effects on aneurysm progression.

Background Marfan syndrome (MFS) is associated with progressive aortic and valvular disease requiring cardiac surgery, but contemporary data on repeat cardiac operations in adults remain limited. Methods We performed a retrospective multicentre cohort study of 783 adults with MFS evaluated across three Mayo Clinic sites. Cardiac operations, postoperative complications, echocardiographic findings and redo sternotomy events were identified by chart review. Multivariate logistic regression was used to evaluate factors associated with redo sternotomy. Results Overall, 454 patients (58.0%) underwent at least one cardiac operation, and 185 patients (23.6% of the total cohort; 41.0% of operated patients) required redo sternotomy. The most common procedures were aortic root intervention (53.4%), aortic valve intervention (39.6%), mitral valve intervention (16.1%) and tricuspid valve intervention (2.6%). Valvular abnormalities were frequent, including mitral regurgitation (51.5%), mitral valve prolapse (41.1%), tricuspid regurgitation (44.6%) and aortic regurgitation (28.5%). Major postoperative complications occurred in 15.3% of patients. On multivariate analysis, hypertension (OR 2.39, 95% CI 1.54 to 3.72), emergent initial operation (OR 3.38, 95% CI 1.97 to 5.80) and postoperative complications (OR 2.59, 95% CI 1.58 to 4.27) were independently associated with redo sternotomy, whereas repair extending beyond the aortic root was associated with lower odds (OR 0.39, 95% CI 0.29 to 0.53). Conclusion In this large multicentre cohort of adults with MFS, cardiac surgery was common, and redo sternotomy occurred frequently among operated patients. These findings provide a contemporary description of the long-term need for cardiac surgery in adults with MFS managed at tertiary referral centres.

This cross-sectional study investigates the association between lipoprotein(a) levels and risk of ventricular arrhythmias among patients with heart failure with reduced ejection fraction receiving implantable cardioverter-defibrillator therapy.

Background The prevalence and clinical correlates of extra-aortic vascular disease in Marfan syndrome remain incompletely defined, and current surveillance strategies primarily target the thoracic aorta. Methods We conducted a multicentre retrospective cohort study of 783 patients with Marfan syndrome across three tertiary centres, with systematic chart and imaging adjudication to define aneurysm and dissection distribution. Results Extra-aortic aneurysms were identified in 32% of patients, most commonly involving the iliac, carotid and subclavian arteries. Extra-aortic dissections occurred in 5.2%. Extra-aortic aneurysms clustered strongly with markers of advanced aortic disease, including abdominal aortic aneurysm (adjusted OR 3.48), prior aortic dissection (OR 3.39) and extra-aortic dissection (OR 4.44), as well as age >40 years and male sex. Genetic confirmation status was not associated with extra-aortic aneurysm presence. Conclusions Extra-aortic vascular involvement is common in Marfan syndrome and closely linked to advanced aortic pathology. These findings support risk-stratified vascular imaging beyond the thoracic aorta in higher-risk patients.

Coronary microvascular dysfunction (CMD) has emerged as a crucial contributor to cardiovascular morbidity and mortality, particularly in patients with ischemia and non-obstructive coronary arteries (INOCA). The condition arises from a complex interplay of structural and functional abnormalities within the small coronary vessels, driven by underlying molecular mechanisms including endothelial nitric oxide synthase (eNOS) uncoupling, oxidative stress, and chronic inflammation. Lipid metabolism plays a central role in this pathology, especially in the setting of elevated low-density lipoprotein cholesterol (LDL-C). Furthermore, the protective capacity of high-density lipoprotein (HDL) is increasingly understood to depend on its functionality rather than absolute levels, as it can become dysfunctional and pro-inflammatory in pathological states. Emerging evidence has identified lipoprotein(a) [Lp(a)] and triglyceride-rich lipoproteins as significant, independent contributors to microvascular injury. Comprehensive clinical assessment of microvascular dysfunction therefore requires integration of advanced lipid profiling, including apolipoprotein B (ApoB), [Lp(a)], and the triglyceride-glucose (TyG) index with invasive and non-invasive measures of coronary flow reserve to more precisely stratify risk. In this narrative review, we synthesize current observational, mechanistic, and early interventional data linking diverse lipid phenotypes to coronary microvascular dysfunction. We propose a concept of lipid-driven CMD endotypes, such as ApoB-/particle overload, dysfunctional HDL, Lp(a)-mediated risk, and metabolic/TyG-high states, and map these to a practical, mechanism-informed management framework. While intensive LDL-C lowering with high-intensity statins and combination therapy remains guideline-directed care for high-risk patients, evidence for dedicated microvascular benefit from newer lipid and cardiometabolic agents is still largely hypothesis-generating. A personalized approach that aligns lipid phenotyping, CMD endotyping, and existing guideline-based therapies may help refine risk assessment and inform future trials.

Background: Hepatocellular carcinoma (HCC) has a poor long-term prognosis due to high recurrence and cirrhosis-related mortality, even after potentially curative treatments such as liver transplantation (LT), surgical resection, or ablation. This study aimed to identify factors associated with ≥10-year survival in HCC patients. Methods: A retrospective cohort study was conducted among HCC patients diagnosed between 2004 and 2022 using the National Cancer Database. Multivariable Cox regression was used to identify predictors of overall survival, and logistic regression was used to identify predictors of ≥10-year survival. Results: Among 249,600 HCC patients, 177,585 (71.2%) died within 5 years, 8613 (3.5%) died at 5–10 years, 54,988 (22.0%) were alive with <10 years of follow-up, and 8219 (3.3%) survived ≥10 years. LT, resection, and ablation were performed in 6.6%, 9.3%, and 11% of patients, respectively. Compared with ablation as the reference group, LT [adjusted odds ratio (aOR) 11.96, 95% confidence interval (CI): 11.27–13.29] and resection (aOR: 2.83, 95% CI: 2.57–3.08) increased the odds of ≥10-year survival, while non-curative treatments reduced the odds compared with ablation (aOR: 0.50, 95% CI: 0.47–0.55). Cox regression results were consistent with the logistic model, confirming the association. Decision tree analysis confirmed LT as the dominant determinant of long-term survival. Black individuals were associated with lower odds of ≥10-year survival (aOR: 0.88, 95% CI: 0.820–0.96) and decreased likelihood of receiving LT (aOR: 0.73, 95% CI: 0.55–0.96). Conclusions: LT offers the best chance of ≥10-year survival in HCC. Ensuring equitable access is essential, especially for Black patients who have lower transplant rates and worse outcomes.

Abstract Background Accurate assessment of left ventricular outflow tract (LVOT) gradients is critical for hypertrophic cardiomyopathy (HCM) management, yet Doppler-based measurements are technically demanding and require expertise. Objective To develop a multi-view deep learning model capable of classifying LVOT obstruction (> 20mmHg) using routine 2D echocardiographic windows without reliance on Doppler imaging. Methods We trained and externally validated a cross-attention-based video-to-video fusion framework that integrated EchoPrime-derived video representations from three standard transthoracic echocardiographic views to classify LVOT gradients. Results Training was performed on a derivation cohort (N = 1833) from a tertiary care system in the United States, with model performance evaluated on an internal held-out test set (N = 275) and a Korean external validation cohort (N = 46). Single-view baselines showed limited discrimination (external AUROCs 0.47–0.70). Conversely, domain-specific foundational model (EchoPrime) achieved superior single-view performance (AUROCs 0.75–0.80 internal; 0.79–0.83 external), highlighting the importance of echo-specific pretraining and temporal modeling. The proposed multi-view fusion further enhanced predictive performance, with the late fusion model reaching an AUROC of 0.84 on the external cohort with significant population-shift. Conclusions These results suggest LVOT physiology is encoded in routine 2D imaging and can be leveraged for clinically relevant gradient classification without Doppler input- proposed AI-guided strategy demonstrates substantial cost savings compared with the screen-all approach. By integrating complementary spatial-temporal information across multiple views, our approach generalizes robustly across populations and may enable real-time decision support, extend LVOT assessment to portable or resource-limited settings, and complement Doppler-based evaluation for longitudinal HCM management.

Background In low-gradient severe aortic stenosis (AS), reduced left ventricular ejection fraction (LVEF <50%) is practically used to define low flow and prompt dobutamine stress echocardiography to discern pseudo-severe AS. In patients with preserved LVEF, stroke volume index (SVI) <35 mL/m² is typically used. However, both are volume-based surrogates. Transaortic flow rate (TAFR), calculated as stroke volume divided by left ventricular ejection time, may better reflect true flow. Nonetheless, comparative data between TAFR and established metrics remain limited. We aimed to evaluate the prognostic value of TAFR in symptomatic low-gradient severe AS. Methods We retrospectively identified patients with low-gradient severe AS (AVA ≤1 cm 2 and peak velocity (Vmax) <4 m/s or mean gradient (MG) <40 mm Hg) who underwent transcatheter aortic valve replacement at Mayo Clinic sites (2017–2023). The primary outcome was 1-year all-cause mortality. Survival was assessed using Kaplan-Meier and Cox proportional hazards models. Results Among 475 patients included (mean age 85±8 years; 49% women), 242 (51%) had TAFR <220 mL/s, 165 (35%) had EF <50%, and 221 (47%) had SVI <35 mL/m 2 . Low TAFR was significantly associated with higher 1-year mortality even after stratifying by EF or SVI. In multivariate analysis, TAFR was an independent predictor of mortality (HR 2.38; 95% CI 1.19 to 4.76, p=0.014) after adjusting for reduced LVEF, low SVI, gender, chronic kidney disease and mitral and tricuspid regurgitation. Conclusions In patients with symptomatic low-gradient severe AS, low TAFR, not SVI or LVEF, is independently associated with mortality and may offer more accurate measure of flow state for clinical staging.