The American Journal of Cardiology

Background: Chronic total occlusions (CTOs) are a common manifestation of coronary artery disease (CAD) and are associated with increased long-term mortality. While successful CTO revascularization improves symptoms and quality of life, a consistent mortality benefit has not been demonstrated in randomized trials. Outpatient cardiac rehabilitation (CR) has proven benefits in improving functional status, exercise capacity, and quality of life in patients with CAD, yet its impact on CTO patients has not been well studied. Objective: To evaluate the association between CR and long-term outcomes in CTO patients. Methods: Using the TriNetX Research Network, we analyzed de-identified patient data from 75 healthcare organizations using ICD codes. The study population included patients with CTO who started CR within 3 months of diagnosis vs patients with CTO who did not engage in CR. A secondary analysis was also conducted, which excluded patients with other indications for CR, including prior coronary artery bypass grafting (CABG) and prior or concurrent percutaneous coronary interventions (PCI). Results: Of 167,176 CTO patients, 10,021 enrolled in CR, including 1,608 without another CR indication. Patients were propensity-matched for independent risk factors for mortality. After 5 years, CR participation was associated with a significant reduction in mortality (HR 0.68; 95% CI, 0.61-0.75; p < 0.0001). This benefit was preserved even after excluding prior revascularization (HR 0.81; 95% CI, 0.67-0.99; p < 0.036). Conclusion: This study demonstrates that cardiac rehabilitation is associated with improved long-term survival in patients with CTOs.

BACKGROUNDPatients with severe aortic stenosis (AS) exhibit heterogeneous flow-gradient hemodynamics and ventricular remodeling, which may influence symptomatic, functional, and structural responses to transcatheter aortic valve implantation (TAVI). Thus, we evaluated differences in functional recovery and reverse remodeling after transfemoral TAVI across flow-gradient phenotypes. METHODSIn this sub-study of the COMPARE-TAVI 1 trial, 975 patients undergoing transfemoral TAVI were classified as classical low-flow low-gradient (cLFLG, 9.1%), paradoxical low-flow low-gradient (pLFLG, 7.7%), low-flow high-gradient (24.7%), normal-flow low-gradient (NFLG, 13.0%), and normal-flow high-gradient (45.4%). The primary functional outcome was longitudinal change in six-minute walk test distance (6MWTD) from baseline to 1 year follow-up. Secondary endpoints included changes in NYHA functional class and reverse remodeling from baseline to 1 year follow-up along with the incidence and risk of all-cause death and a composite MACE-endpoint. RESULTSMean 6MWTD increased by 59{+/-}4 meters at 1-month (p=0.000) with no additional improvement at 1-year, but with heterogeneity between groups (p=0.000). Improvements among NFLG, cLFLG and low-flow high-gradient AS were comparable with normal-flow high-gradient AS, while pLFLG AS exhibited significantly increments at 1-year (-28{+/-}15 meters, p=0.007). Patients with NFLG, cLFLG and pLFLG were more symptomatic at baseline (NYHA [&ge;]III: 40.5%, 57.3% and 50.6%, respectively, p=0.000). NYHA improved in all groups at 1-year follow-up (p=0.000), although persistent symptoms at 1-year were most frequent in pLFLG (NYHA [&ge;]II; 38.7%, p=0.012). Reverse remodeling was also comparable between normal-flow high-gradient AS and NFLG, cLFLG, and low-flow high-gradient AS, respectively, but attenuated in pLFLG AS in both unadjusted and adjusted analyses. No differences were observed in the incidence and risk of all-cause death or the composite MACE-endpoint. CONCLUSIONTAVI associates with functional recovery across all flow-gradient phenotypes, although with heterogeneous responses. Patients with NFLG showed comparable functional recovery and reverse remodeling at 1-year follow-up compared with normal-flow high-gradient AS, whereas pLFLG demonstrated attenuated benefits across all parameters.

Background: Clinical genetic evaluation for patients with dilated cardiomyopathy (DCM) is minimally implemented and models of care are not defined. To understand current genetics care for DCM, a systematic needs assessment was conducted. Methods: Principal Investigators (PIs) of the DCM Consortium convened at the Summer Scientific Symposium in July 2025. An electronic needs assessment was collected from the 24 PIs in advance to define current care models by evaluating which Heart Failure Society of America-recommended genetic evaluation components are conducted, by whom, and time required. Descriptive statistics were generated to characterize model features. Focus group discussions explored barriers and facilitators to implementing genetic services. Results: Four care models emerged from the PI responses: 1 -- Traditional-Synchronous (25%, n=6, requiring the most time per patient), 2 -- Traditional-Asynchronous (33%, n=8), 3 -- Externally Sourced (17%, n=4), and 4 -- Physician/Advanced Practice Provider Conducted (25%, n=6, requiring the least time per patient). All models used genetic testing, whereas other components were implemented variably or not at all. Models 1 (15.7{+/-}4.1) and 2 (15.4{+/-}3.0) were rated more acceptable than Model 4 (9.8{+/-}2.9, 1 vs 4: p=0.027; 2 vs 4, p=0.023). Notably, 88% of PIs used genetic information for treatment decisions, including ICD placement (83%; n=20) or cardiac transplant (63%; n=15). Major facilitator themes from focus group discussions included having a genetic counselor on the HF team and developing authoritative standards directing provision of DCM genetic services. Barrier themes included operational challenges, limited personnel, clinician under-recognition, need for new service delivery models, and billing/reimbursement. Conclusions: DCM genetic care models and components were highly variable across the 24 sites of the DCM Consortium, even though all sites discussed similar factors that enable or hinder implementing genetic services for DCM. Understanding the basis of practice model variability may provide insight to yield more scalable care approaches.

Background: Heart failure (HF) is a major contributor to inpatient hospital utilization, with persistently high 30-day readmission rates. Existing prediction tools are frequently restricted to primary-diagnosis HF admissions, potentially excluding clinically relevant HF-related hospitalizations. Objectives: To develop and validate risk prediction models using machine learning (ML)-based risk prediction models to predict 30-day readmissions among patients with HF using the Kansas Health Information Network, a statewide health information exchange. Methods: This retrospective cohort study analyzed HF hospitalizations using predictors including demographics, comorbidities, laboratory results, medications, clinical quality metrics for diabetes and kidney disease management, and prior healthcare utilization. Five ML models, including regularized logistic regression, random forest, extreme gradient boosting, categorical boosting, and deep neural network, were trained using stratified 5-fold cross-validation. Model performance was evaluated on an independent test set using the area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), misclassification rate (MCR), and Brier score. Results: Among 2,734 HF patients, the 30-day readmission rate was 27%. The XGBoost model achieved the best discrimination (AUROC=0.75; AUPRC=0.58; MCR=0.21). Patients in the highest-risk decile had a positive predictive value of 76%, accounted for approximately one-third of all 30-day readmissions, and had a 3.3-fold enrichment compared with baseline risk. The key predictors included prior hospital utilization, diabetes and kidney disease management indicators, and comorbidity burden. Conclusions: Risk stratification using routinely collected clinical data identified a subgroup at elevated risk for 30-day readmission. These findings support the potential role of data-driven risk prediction to inform targeted transitional care.

BackgroundAnomalous aortic origin of a coronary artery (AAOCA) can cause myocardial ischemia and sudden cardiac death. The optimal stress-testing strategy and impact of coronary morphology on ischemia remain unclear. We assessed the effect of coronary morphology on stress-test completion and results across multiple test modalities. MethodsThis retrospective cohort study included 531 adults with AAOCA at our institution (7/2015 - 3/2023). Coronary morphology was characterized by the anomalous coronary (right [RCA], left main [LMCA], left anterior descending [LAD], left circumflex) and the course type (intramural, interarterial-only, transseptal, and other [prepulmonic and retroaortic]). Exercise and pharmacologic stress tests were positive if ischemia included the territory of the anomalous coronary. A mixed-effect logistic regression modeled the odds of a positive test based on morphology, comorbidities, and modality. A random forest regression analyzed the stress iFR as a continuous outcome. ResultsStress test results were available for 396 (75%) of patients (age 50 {+/-} 17 years; 42% female). Stress testing included 699 ECGs, 198 echocardiograms, 288 SPECTs, 133 PETs, and 103 dobutamine iFR studies. Completion of invasive dobutamine iFR (versus noninvasive-only) stress testing was associated with high-risk coronary morphology, p<0.001. Coronary morphology that trended toward higher adjusted odds of ischemia included the anomalous LMCA (OR: 2.1, p=0.054) and intramural course (OR: 1.9, p=0.14). Compared to ECG, iFR had higher adjusted odds of a positive result (OR: 27, p<0.001), followed by PET (OR: 9.0, p<0.001). In the random forest regression, stress iFR value was lowest for LAD (0.75) compared to LMCA (0.83) and RCA (0.84). For course type, transseptal (strongly correlated with the anomalous LAD) had the lowest stress iFR (0.77), followed by intramural (0.83), and interarterial (0.88). ConclusionsIn our adult AAOCA cohort, high-risk coronary morphology demonstrated a borderline association with ischemia on stress testing, whereas stress test modality was the strongest determinant of ischemia detection. Invasive stress testing was reserved for higher-risk coronary morphology. These findings underscore that effective risk stratification in AAOCA integrates clinical symptoms, coronary morphology, and stress test modality. Long-term follow-up is needed to determine the optimal strategy for ischemia evaluation. Clinical PerspectivesO_ST_ABSWhat is new?C_ST_ABSO_LIIn this single-center registry of adults with anomalous aortic origin of a coronary artery (AAOCA), 75% of patients had stress testing, enabling the largest analysis of how anomalous coronary morphology impacts stress testing practices and the presence of ischemia. C_LIO_LIConsistent with published data in younger AAOCA cohorts, our adult population (mean age >50 years) trended toward increased risk of ischemia with an anomalous left coronary and intramural course. C_LIO_LIComparing various stress test modalities for AAOCA, instantaneous wave-free, followed by positron emission tomography and single-photon emission computed tomography, have higher odds of being positive for ischemia than electrocardiogram and echocardiograms. C_LI What are the clinical implications?O_LIAdults with AAOCA remain at risk for ischemia and require careful risk stratification, with coronary morphology and clinical symptoms informing stress test selection and result interpretation. C_LIO_LIFor higher risk morphologic variants of AAOCA, consider further risk stratification with invasive coronary provocative studies to detect inducible ischemia. C_LI

Background: Red cell distribution width (RDW), a readily available hematological parameter reflecting erythrocyte size heterogeneity, has been increasingly recognized as a prognostic marker in congestive heart failure (CHF), with elevated levels independently associated with adverse outcomes. However, RDW-derived composite indices-particularly the RDW-to-platelet ratio (RPR) and RDW-to-hemoglobin ratio (RHR), which integrate inflammatory, hemostatic, and oxygen-delivery pathways-remain largely unexplored in CHF populations. Whether these indices provide incremental prognostic value beyond RDW alone in critically ill patients with CHF has not been established. Methods: This retrospective cohort study included 30,409 participants from the MIMIC-IV and eICU-CRD databases. Multivariable logistic regression, restricted cubic spline (RCS) analysis, and subgroup analyses were employed to evaluate the associations between RDW, RDW-derived indices (RPR and RHR), and in-hospital mortality in patients with congestive heart failure. Results: Based on a pooled cohort of 30,409 patients with CHF from the MIMIC-IV and multi-center eICU-CRD databases (15,983 and 14,426, respectively), 16,295 (53.6%) were male and 14,114 were female, with a median age of 71.7 years. The mean RDW was 16.0 {+/-} 2.5, and the overall in-hospital mortality rate was 12.6%. Higher RDW quintiles were associated with progressively increased in-hospital mortality. In the fully adjusted model, RDW, RPR, and RHR were all significantly associated with increased in-hospital mortality, with adjusted odds ratios (ORs) of 2.46 (95% CI: 2.17-2.79) for RDW, 1.55 (95% CI: 1.38-1.73) for RPR, and 2.43 (95% CI: 2.09-2.82) for RHR. Sensitivity analyses using restricted cubic splines demonstrated that the association between RDW and RHR with in-hospital mortality was linear (P for nonlinearity > 0.05), whereas that for RPR exhibited a non-linear pattern (P = 0.02 for non-linearity). Conclusions. Elevated RDW, RPR, and RHR were independently associated with increased in-hospital mortality in patients with congestive heart failure. Notably, RPR exhibited a non-linear threshold association with in-hospital mortality.

BackgroundAortic stenosis (AS) carries a high mortality risk if left untreated. Transcatheter aortic valve implantation (TAVI) has emerged as a primary treatment modality for many patients with severe AS. Observational data suggest that renin-angiotensin system (RAS) inhibitor use following TAVI are associated with lower risk, but with divergent reported effects and limited statistical power for specific cardiovascular outcome. This study aimed to assess the association between RAS inhibitor use and clinical outcomes after TAVI. MethodsA systematic literature search was conducted in EMBASE and PubMed. Eligible studies included those reporting on RAS inhibitor use in TAVI populations. The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, myocardial infarction (MI), cerebrovascular events, and heart failure (HF) hospitalization. ResultsNine observational studies including 36,015 patients were included. RAS inhibitor use was associated with lower odds of all-cause mortality (OR 0.74, 95% CI 0.70- 0.78), cardiovascular mortality (OR 0.62, 95% CI 0.55-0.72), cerebrovascular events (OR 0.59, 95% CI 0.47-0.74), and HF hospitalization (OR 0.84, 95% CI 0.77-0.92). No clear association was observed for MI (OR 0.95, 95% CI 0.59-1.53). ConclusionsRAS inhibitor use was associated with favorable clinical outcomes following TAVI. However, these findings are based on observational data, which are subject to residual confounding. Randomized controlled trials are needed to clarify the clinical utility of RAS inhibitors in this setting.

BackgroundAngina with nonobstructive coronary arteries (ANOCA) is a heterogeneous condition encompassing distinct endotypes representing different underlying pathophysiological mechanisms. Endothelial dysfunction is considered a central hallmark of ANOCA. However, studying patient-derived endothelial cells (ECs) remains challenging due to the limited availability of disease-specific endothelial samples. We therefore aimed to assess the feasibility of isolating and culturing ECs from catheterization material obtained during routine coronary function testing in ANOCA patients. MethodsCatheterization material was collected from 79 ANOCA patients (84% female, age 58{+/-}10 years) undergoing coronary function testing. ECs were isolated, expanded and characterized using immunostaining, flow cytometry, gene expression profiling and functional assays. ResultsEC isolation was successful in 43% of cases and resulted in 34 primary EC cultures that were expanded up to passage 10. Isolation success was independent of clinical or procedural characteristics. Isolated cells exhibited typical EC morphology and expressed EC markers confirmed by immunostaining, flow cytometry and gene expression analyses. EC marker gene expression remained largely stable over passages. However, stress- and defense-related gene expression programs increased over time, while proliferation-related processes decreased. Functional assays demonstrated that the coronary catheterization-derived ECs showed typical properties of wound healing, angiogenesis, activation responses upon stimuli and monocyte adhesion. ConclusionsThis study demonstrates the feasibility of isolating and expanding ECs directly from catheterization material collected during routine coronary function testing in ANOCA patients. These patient-derived ECs retain characteristic endothelial features and functionality. This approach offers primary EC cultures to study the mechanisms underlying endothelial dysfunction in ANOCA. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=186 SRC="FIGDIR/small/26350551v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@5655d3org.highwire.dtl.DTLVardef@1cab83org.highwire.dtl.DTLVardef@4055baorg.highwire.dtl.DTLVardef@1bc3d08_HPS_FORMAT_FIGEXP M_FIG C_FIG PerspectivesO_ST_ABSClinical perspectiveC_ST_ABSWhat is new?O_LIWe established a method to isolate and culture endothelial cells from routine coronary catheterization material in patients with ANOCA, enabling direct study of patient-specific endothelial dysfunction. C_LIO_LIThe patient-derived endothelial cells exhibit characteristic morphology, express canonical endothelial markers and retain functional properties consistent with endothelial physiology. C_LI What are the clinical implications?O_LIThis approach provides a clinically relevant platform to investigate mechanisms underlying ANOCA and may support the development of personalized diagnostic and therapeutic strategies. C_LIO_LIBroader application of this method could facilitate translational research in other vascular pathologies where access to endothelial tissue is limited. C_LI

BackgroundAn elevated calcium-phosphate product (CPP), defined as a product of serum calcium and serum phosphate, is a hallmark of CKD-mineral and bone disorder and has been implicated in accelerated coronary artery calcification, arterial stiffness, and left ventricular hypertrophy. These pathological changes contribute to adverse cardiovascular outcomes. While prior studies have shown worse percutaneous coronary outcomes (PCI) outcomes in CKD patients overall, the prognostic impact of CPP levels remains underexplored. The objective is to evaluate post-PCI outcomes in CKD patients with and without hypercalcemia and hyperphosphatemia. MethodsA retrospective cohort analysis was conducted using the TriNetX U.S. Collaborative Network, focusing on adult patients with CKD undergoing PCI. Patients were grouped based on serum calcium and phosphorus levels, with those having hypercalcemia and hyperphosphatemia compared to those without. Diagnoses and procedures were identified using ICD-10 and CPT codes. Propensity score matching was applied to account for differences between groups. Post PCI outcomes were analyzed. Primary outcome was all-cause mortality. Secondary outcomes encompass coronary artery bypass grafting (CABG), myocardial infarction (MI), in-stent re-stenosis [redo PCI] and target vessel revascularization, heart failure (HF) exacerbations, and peri-/ post-procedural complications were assessed within a 5-year follow-up period. Kaplan-Meier analysis with log-rank was used for statistical comparisons, with significance set at p<0.05. ResultsThe elevated CPP group was significantly associated with increased post-PCI all-cause mortality [hazard ratio (HR) 1.428], in-stent restenosis [HR 1.589], heart failure exacerbations [HR 1.492], and recurrent angina or MI [HR 1.396]. No significant differences were found in rates of post PCI CABG, periprocedural complications (postprocedural cardiac insufficiency, postprocedural cardiac arrest, postprocedural heart failure, intraoperative cerebrovascular infarction, postprocedural cerebrovascular infarction, and intraoperative cardiac arrest), or redo PCI. ConclusionIn this propensity score-matched analysis, elevated CPP in CKD patients undergoing PCI was independently associated with worse outcomes, including higher mortality and cardiovascular event rates. These findings highlight the prognostic value of CPP and the need for closer metabolic monitoring and individualized risk stratification. O_FIG O_LINKSMALLFIG WIDTH=177 HEIGHT=200 SRC="FIGDIR/small/26347359v1_ufig1.gif" ALT="Figure 1"> View larger version (50K): org.highwire.dtl.DTLVardef@198df1forg.highwire.dtl.DTLVardef@160722borg.highwire.dtl.DTLVardef@e796fforg.highwire.dtl.DTLVardef@6a40d6_HPS_FORMAT_FIGEXP M_FIG C_FIG

Background: The prevalence of heart failure (HF) is increasing worldwide, and rehospitalizations due to exacerbations remain a major clinical and economic burden. Beyond medical triggers, insufficient patient understanding and inadequate self-management often contribute to recurrent admissions. The Kurume-HEARTS program was developed to provide regular planned hospitalizations incorporating structured education, cardiac rehabilitation, and medication adjustment for patients with recurrent HF. Objective: To retrospectively evaluate the clinical and economic impact of the Kurume-HEARTS program. Methods: We enrolled consecutive patients with recurrent HF hospitalizations who underwent the program at Kurume University Hospital between January 2020 and October 2025. Outcomes compared planned versus unplanned hospitalizations within the same patients. Co-primary endpoints were total hospitalization cost and total length of stay per person-year. Secondary endpoints included per-hospitalization cost, length of stay, unplanned and planned admission frequency, and NT-proBNP levels at admission. Results: Of 31 screened patients, 20 with recurrent heart failure were included. During a median follow-up of 27.1 months, 135 hospitalizations occurred (69 unplanned and 66 program-based). Total hospitalization cost per person-year was significantly lower during the Kurume-HEARTS program than during unplanned hospitalizations, while length of stay per person-year tended to be shorter. Per-admission cost and length of stay were significantly lower with the program, without differences in admission frequency. NT-proBNP levels at admission were higher during unplanned hospitalizations, indicating greater clinical instability. Conclusions: The Kurume-HEARTS program can help reduce the cost and hospitalization length of unplanned admissions by enabling earlier intervention and structured inpatient management.

BackgroundThe incidence of sudden cardiac arrest (SCA) manifesting as pulseless electrical activity (PEA) has increased, and survival remains extremely low. Methods for early identification and management of high-risk individuals are needed, but no clinical risk scores currently exist to predict PEA-SCA. Our objective was to develop and validate a clinical prediction model for PEA-SCA. MethodsFrom an ongoing prospective, population-based study of SCA in Portland, Oregon (catchment pop. {approx}1 M, 2002-2020), we identified PEA-SCA adults. Lifetime clinical records were compared with those of a control group with >50% prevalence of significant coronary disease. Prediction models were constructed using backwards stepwise logistic regression in a training dataset (67%) and evaluated in a validation dataset (33%). Model discrimination was assessed using receiver operating characteristic curves (C statistic). External validation was performed in a geographically distinct population in Ventura County, California (population {approx}850,000, 2015-2022). ResultsThe final clinical algorithm (PEA-Risk) incorporating 12 clinical, electrocardiogram and medication variables demonstrated strong discrimination in the training dataset (C statistic = 0.860 [95% CI: 0.838-0.881]) and remained robust in internal (C statistic = 0.832 [95% CI: 0.800-0.865]) and external validation datasets (C statistic = 0.704 [95% CI: 0.665-0.743]). ConclusionsWe developed and externally validated a clinical algorithm for predicting PEA-SCA. Given the low rates of successful resuscitation after PEA arrest, this risk prediction tool may enable earlier identification and prevention of PEA-SCA. Clinical PerspectiveO_ST_ABSWhat is knownC_ST_ABSO_LIThe proportion of SCA presenting as pulseless electrical activity (PEA) is increasing, and survival from these events remains extremely low. C_LIO_LIThe are no available methods for clinical risk prediction of these events. C_LI What the study addsO_LIThe present study constructs and replicates a risk score for prediction of SCA manifesting with PEA using widely available clinical and noninvasive markers. C_LIO_LIThese findings have implications for developing prevention and management strategies for individuals at high risk of PEA-SCA. C_LI

BackgroundChagas cardiomyopathy remains a major cause of heart failure (HF) in endemic regions and is increasingly recognized globally, yet data on in-hospital outcomes are limited. Objective: To assess whether Chagas disease is associated with higher in-hospital mortality among patients hospitalized with HF. MethodsWe analyzed a nationwide administrative database from the Brazilian Unified Health System (DATASUS/SIHSUS), including adults hospitalized with HF between April 2017 and August 2021. HF was identified using ICD-10 code I50.x and Chagas disease using B57.x. The primary outcome was in-hospital mortality, evaluated using multivariable Cox models. Results: Among 910,128 HF hospitalizations, 1,082 (0.12%) were associated with Chagas disease. Patients with Chagas were younger but had a more complex clinical profile and higher resource use. In-hospital mortality was higher in the Chagas group (25% vs 12%; p<0.001). After adjustment, Chagas disease remained independently associated with mortality (HR 1.54; 95% CI 1.35-1.75; p<0.001). ConclusionsIn this large real-world cohort, Chagas disease was associated with higher in-hospital mortality and greater healthcare utilization. These findings reinforce the high-risk nature of Chagas cardiomyopathy and point to the need for more targeted treatment strategies. What is the clinical question being addressed?Chagas cardiomyopathy is a major cause of heart failure in endemic regions and an emerging global health problem, yet real-world data on in-hospital outcomes remain limited. Is Chagas disease associated with higher in-hospital mortality? What is the main finding?Chagas disease was independently associated with a 54% higher risk of in-hospital mortality in a large real-world cohort.

Background Myocardial remodeling precedes symptomatic heart failure, which is important to detect early. We assessed feasibility and clinical correlates of a novel integrated assessment of myocardial remodeling in a large rural cohort in the Southeastern United States. Methods Echoes were obtained with AI assistance (Caption guidance) in 3100 adults in the NHLBI-funded RURAL cohort study. Of those, 1895 had quantifiable global longitudinal strain (GLS), left ventricular mass (LVM), and left atrial volume (LAV). LV-LA Health was based on a simple count of sex-specific abnormalities (0-3), indexed to body surface area (BSA) or height (Table 1). Relationships with demographics and risk factors were compared with Spearman correlation and Mantel-Haenszel tests, with moderate and severe results combined. Results Median (IQR) age was 49 (40-58). Impaired LV-LA Health is common even in a low PREVENT cardiovascular (CV) risk population (median 10-year risk 3.3%; 25th, 75th 1.2,7.2) with preserved ejection fraction (EF; 60%; 57,62). The prevalence of abnormalities differed greatly by indexing method: 18.2% with BSA (15.1% mild; 3.1% mod/severe) vs 51% with height (38.3% mild; 12.7% mod/severe) (Figure 1). LV-LA impairment increased with age, PREVENT CV risk score and cardiovascular risk factors (hypertension, diabetes, dyslipidemia, obesity); all p<0.001. Impairment was more common in Black vs White people (p<0.001) and differed by sex only with height indexation. Conclusions A novel LV-LA health composite of routinely acquired echocardiographic measures identifies substantial subclinical cardiac remodeling in a middle-aged rural community cohort, not detected by PREVENT score or ejection fraction. This is the first application of this framework in a large, unselected community sample. Indexation method affects prevalence, with BSA likely underestimating risk in adiposity-enriched populations. Findings suggest a high rural burden and longitudinal evaluation with future CV events is ongoing.

Background: Detection of disease progression is key to personalize treatment strategies in transthyretin cardiomyopathy (ATTR-CM), particularly with emerging therapies. Echocardiography can detect subtle longitudinal changes but is limited by operator dependence. This study evaluates agreement and reproducibility of fully automated, AI-assisted echocardiographic measurements under real-world conditions. Methods: This retrospective study included 62 patients with ATTR-CM undergoing 178 serial annual echocardiograms assessed by a reference cardiologist, a second cardiologist, a novice reader, and a fully automated AI algorithm (Us2.ai). Interrater agreement was assessed using Bland-Altman analysis and intraclass correlation coefficients (ICCs). Intrarater variability for human readers was derived from repeated blinded measurements, with limits of agreement (LoA = mean difference +/- 1.96 x SD) defining the smallest detectable change. AI repeatability was assessed using within-study pairwise differences. Results: AI showed moderate agreement with the reference cardiologist for IVSd and LVEDV (ICC 0.65 and 0.51), with biases of -1.9 mm and -39 mL, respectively. Interrater agreement between cardiologists was good (ICC 0.79 and 0.84) with minimal bias (-0.2 mm and +3 mL). Intrarater variability was moderate to excellent for both cardiologists (LoA 3.0 mm and 43 mL for the reference cardiologist; 2.7 mm and 31 mL for the second cardiologist). AI demonstrated comparable repeatability (LoA 3.6 mm and 37 mL), while the novice showed higher variability (5.1 mm and 61 mL). Conclusion: AI-based measurements demonstrated repeatability comparable to experienced cardiologists. Despite moderate agreement and systematic differences in volumetric assessments, their reproducibility supports automated analysis for longitudinal echocardiographic monitoring.

Aims: Dynamic left ventricular outflow tract obstruction (LVOTO) is a hemodynamically significant complication following transcatheter aortic valve replacement (TAVR) that remains difficult to predict with conventional transthoracic echocardiography (TTE). We examined whether a deep learning (DL) model developed for LVOTO detection in hypertrophic cardiomyopathy (HCM) could predict post-TAVR LVOTO from pre-TAVR TTE in patients with severe aortic stenosis (AS). Methods and Results: In this retrospective study of 302 consecutive patients undergoing TAVR for severe AS, a pre-trained DL model was applied to pre-TAVR TTE to generate a patient-level DL index of LVOTO (DLi-LVOTO; range 0-100). Post-TAVR LVOTO was defined as a peak pressure gradient [&ge;]30 mmHg on follow-up TTE. Logistic regression and receiver operating characteristic analyses assessed the association and discriminative performance of DLi-LVOTO. Pre-TAVR LVOTO was present in 32 patients (10.6%) and post-TAVR LVOTO in 35 (11.6%). Follow-up TTE was performed at a median of 47 days (IQR 37-63) after TAVR, with the majority of TTE (216 of 302, 71.5%) performed within 2 months. DLi-LVOTO was significantly higher in patients with LVOTO at both pre- and post-TAVR TTE (all p<0.001). In multivariable analysis, DLi-LVOTO remained independently associated with post-TAVR LVOTO even after adjusting for conventional TTE parameters and pre-TAVR LVOTO (adjusted OR 1.29, 95% CI 1.06-1.56 per 10-score increase, p=0.011), with an AUROC of 0.78 (95% CI 0.72-0.85). Among patients without pre-TAVR LVOTO, DLi-LVOTO retained independent predictive value (adjusted OR 1.56, 95% CI 1.19-2.06, p=0.001; AUROC 0.84, 95% CI 0.77-0.91). Conclusion: A DL model originally trained in HCM patients independently predicts post-TAVR LVOTO from pre-TAVR TTE, including in patients without pre-existing LVOTO, suggesting it captures hemodynamic features beyond conventional echocardiographic assessment.

Background Exercise capacity varies among individuals with a Fontan circulation. Percent predicted peak oxygen consumption (%pVO2) may be influenced by ventricular morphology, Fontan subtype, and conduit characteristics, but data explaining variability in exercise capacity are limited. This study examined whether anatomical and surgical factors are associated with %pVO2 later in life. Methods Participants enrolled in the multicenter Single Ventricle Outcomes Network (SV-ONE) database who had cardiopulmonary exercise testing (CPET) data were included. Published reference equations were used to estimate %pVO2. Multivariable regression models evaluated associations between anthropometric, anatomical (diagnosis and dominant ventricle), and surgical (Fontan subtype, conduit size, and surgical era) factors and %pVO2. Restricted spline analyses assessed nonlinearity. Results 561 individuals with a Fontan circulation were included in the analysis; age 20 {+/-} 8 years, 54% male, mean %pVO2 was 63 {+/-} 16%. Sex and exercise modality were the strongest predictors of %pVO2, with females being 12% higher than males and treadmill 4.6% higher than a cycle. Age at CPET was a predictor of exercise capacity with %pVO2 decreasing by 0.8% per year. Ventricular morphology, diagnosis, and Fontan subtype did not have a statistical association with the primary outcome. In models restricted to patients with an extracardiac conduit (n = 330), conduit diameter and area were not associated with %pVO2, even after indexing to body surface area. Univariable nonlinear spline analyses suggested an optimal conduit size of 18 mm for %pVO2, but this was not significant after body size adjustments. Conclusion In this large multicenter cohort, surgical and anatomical features were not as important as sex, age, and body size as determinants of exercise performance in patients with a Fontan circulation. Reduced exercise capacity in this population appears to reflect progressive pathophysiological changes of the Fontan circulation rather than specific characteristics such as conduit size, ventricular morphology, or anatomy.

Background: Heterotopic caval valve implantation using the TricValve(R) (OrbusNeich P&F) is a unique interventional approach for treatment of severe Tricuspid Regurgitation in patients who are deemed ineligible for surgery. Given the complexity and novelty of TricValve(R) implantation, there is a pressing need for robust clinical data to evaluate its safety, efficacy, and long-term outcomes. Our study assesses the clinical results of patients followed up for 1 year from our center. Methods: Retrospective, single center registry involving patients who have undergone TricValve(R) Transcatheter Bicaval Valves System (OrbusNeich P&F) implantation for the treatment of severe tricuspid regurgitation. Results: Fourteen patients were included. The mean age was 67.5 {+/-} 8.7 years, with high surgical risk (mean EuroSCORE II 6.1 {+/-} 3.7). Procedural success was achieved in thirteen patients, with no reported in-hospital mortality or stroke among all fourteen patients. At 1-year, significant improvements were observed in New York Heart Association (NYHA) functional class (86% Class III at baseline to 0% Class III at 1 year, P=0.002) and Kansas City Cardiomyopathy Questionnaire (KCCQ-12) scores (mean 32.0 {+/-} 7.4 to 42.4 {+/-} 12.0, P=0.015). TR Regurgitant Volume significantly decreased (65.5 {+/-} 16.9 ml to 38.2 {+/-} 13.6 ml, P=0.005). No deaths or strokes occurred during follow-up. Rehospitalization due to heart failure occurred in 14% (2 out of 14) of patients. Conclusion: In this single-center registry of high-risk patients, TricValve(R) implantation was associated with a favorable safety profile, significant reduction in tricuspid regurgitant volume, and meaningful improvements in functional status and quality of life at 1 year follow-up.

BackgroundST-elevation myocardial infarction (STEMI) is reported to be a leading cause of mortality worldwide. While cardiac troponins are the gold standard for myocardial injury detection but creatine kinase-MB (CK-MB) and total creatine phosphokinase (CPK) retain prognostic use in resource-limited settings. ObjectiveTo evaluate the prognostic significance of admission CK-MB and CPK levels in STEMI patients and to assess their association with hematological parameters for integrated risk stratification. MethodsThis cross-sectional study enrolled 15 consecutive STEMI patients from the Punjab Institute of Cardiology, Lahore, during January 2024. Comprehensive laboratory analysis including cardiac biomarkers (CK-MB, CPK, troponin-I, LDH), complete blood count, renal function, serum electrolytes, and metabolic parameters, was performed on admission. Pearson correlation and comparative statistical analyses were also conducted to assess the relationships between cardiac biomarkers and hematological indices. ResultsThe cohort includes 15 patients (mean age 50.1 {+/-} 12.2 years; 73.3% male). Cardiac biomarker elevation was prevalent: CK-MB was elevated in 12/15 (80%), CPK was elevated in 12/15 (80%), with concordant elevation in 11/15 (73.3%), which indicates extensive myocardial necrosis. Troponin-I showed the highest elevation rate at 13/15 (86.7%). Hematological abnormalities included anemia (60%), WBC elevation (53.3%), and RBC reduction (40%). Random glucose averaged 150.80 {+/-} 63.55 mg/dL, with 66.7% highlighted the hyperglycemia. Remarkably, electrolyte balance was preserved in all of the patients (0% sodium, potassium, and bicarbonate abnormalities), indicating maintained homeostasis. Pearson correlation analysis revealed a significant correlation between CK-MB and CPK (r = 0.615, p = 0.0126), while correlations between cardiac biomarkers and hematological parameters were weak (p > 0.05). Risk stratification identified 53.3% of patients as high-risk who required intensive management. ConclusionsCK-MB and CPK demonstrate significant concordance and retain prognostic value in STEMI patients, particularly in resource-limited settings where troponin access may be constrained. While troponin-I remains the most sensitive biomarker, combined assessment of conventional cardiac enzymes supports reliable evaluation of myocardial injury. Hematological parameters reflect systemic response but show limited correlation with cardiac biomarkers.

PurposeObstructive sleep apnea (OSA) is a common comorbidity in heart failure (HF) patients with prevalence increasing as HF severity worsens. While CPAP/BiPAP has been shown to reduce disease burden and mortality in the general HF population, it is unclear whether these benefits extend to patients with left ventricular assist devices (LVADs). We sought to determine whether OSA affects long-term survival in newly implanted LVAD patients and whether CPAP/BiPAP treatment confers mortality benefits. MethodsThis single-center retrospective study included patients who underwent LVAD implantation between January 2007 and February 2022. Recipients were stratified by OSA status (OSA vs No-OSA), and those with OSA were further categorized based on CPAP/BiPAP compliance. Comparative statistics and Kaplan-Meier survival analyses were performed, with log-rank tests used to compare groups and assess survival differences. A Cox proportional hazards model was conducted to evaluate the association between risk factors and survival among patients with OSA and No-OSA. ResultsBefore LVAD implantation, patients with OSA had higher body mass index, hypertension, and a higher rate of implantable cardioverter-defibrillator placement than those without OSA. OSA was not associated with increased postoperative complications. Although survival did not differ significantly between OSA and No-OSA patients (p=0.33), CPAP/BiPAP-compliant OSA patients had significantly better survival than noncompliant patients (p=0.0099). ConclusionsLVAD patients with OSA who consistently use CPAP/BiPAP have better survival than those who do not. CPAP/BiPAP is a simple, low-risk treatment that can reduce mortality in this population. Therefore, increased perioperative screening for OSA should be considered for patients receiving LVADs. Multicenter studies are needed to confirm our findings further.

BackgroundPatients with heart failure and reduced ejection fraction (HFrEF) commonly show signs of systemic inflammation. Interleukin-1 (IL-1) is a pro-inflammatory cytokine, known to modulate cardiac function. We aimed to determine the effects of treatment with anakinra, recombinant IL-1 receptor antagonist (IL-1Ra), on plasma IL-1Ra levels. MethodsWe measured IL-1Ra levels at baseline and longest available follow-up to 24 weeks in 63 patients (44 males, 40 self-identified Black-Americans) with recent hospitalization for HFrEF, and systemic inflammation (C-reactive protein [CRP] levels >2 mg/L) who were assigned to anakinra (n=42 [66.7%]) or placebo (n=21 [33.3%]) as part of the REDHART2 clinical trial (NCT0014686). Cardiorespiratory fitness was measured as peak oxygen consumption (VO2peak). ResultsBaseline plasma IL-1Ra levels were 380 [290 to 1046] pg/mL. On-treatment IL-1Ra levels were significantly higher in the patients treated with anakinra vs. placebo (3,994 [3,372 to 5,000] pg/mL vs. 492 [304 to 1370] pg/mL, P<0.001). The longest available follow-up was 6 weeks in 10 patients (15.9%), 12 weeks in 12 patients (19%), and 24 weeks in 41 patients (65.1%). On-treatment IL-1Ra levels and interval change in IL-1Ra showed a modest inverse correlation with on-treatment CRP levels (R=-0.269, P=0.033 and R=-0.355, P=0.004, respectively) and no statistically significant correlations with VO2peak values (P>0.05). ConclusionsPatients with recently decompensated HFrEF and systemic inflammation treated with recombinant IL-1Ra, anakinra, have a significant several-fold increase in plasma IL-1Ra levels. On-treatment IL-1Ra levels however show only a modest correlation with CRP levels and not with (VO2peak).