The American Journal of Cardiology

Background Although atrial fibrillation (AF) frequently coexists with degenerative mitral regurgitation (DMR), imaging assessment of left atrial (LA) fibrosis in this population remains limited. We integrated echocardiographic and cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) parameters to characterize LA remodeling features in isolated DMR and assess its association with AF. Methods In this retrospective study, consecutive patients with moderate-to-severe or severe isolated DMR who underwent echocardiography and CMR, including cine and LGE sequences, between February 2025 and January 2026 were included. Patients with other left-sided valvular disease of mild or greater severity or cardiomyopathy were excluded to isolate a population of "pure" DMR patients, and LALGE percentage was calculated as LALGE area divided by left atrial wall area. Imaging parameters were compared according to AF status and evaluated using logistic regression and receiver operating characteristic (ROC) analysis. Multimodality models were constructed to assess the combined discriminative value of echocardiographic and CMR parameters. Results Among 46 patients with DM (71.7% male, 62.0 years of age), 17 (37.0%) had AF. Compared with patients without AF, AF patients were older (P=0.005) and had lower LA reservoir strain [LASr; adjusted odds ratio (OR) 0.86; 95% confidence interval (CI) 0.76-0.94; P<0.001], higher left atrioventricular coupling index (LACI; adjusted OR per 10-percentage-point increase, 1.48; 95% CI, 1.18-2.23; P<0.001), larger LALGE area (adjusted OR 1.20; 95% CI, 1.07-1.41; P<0.001), higher LALGE percentage (adjusted OR 1.19; 95% CI, 1.02-1.42; P=0.025). Among single parameters, LACI showed the highest area under the curve (AUC 0.85, 95% CI 0.72-0.99; cutoff 58.59%), whereas LALGE area showed an AUC of 0.78 (95% CI 0.61-0.94; cutoff 13.73 cm2). Among all models, LASr combined with LALGE percentage achieved the highest AUC (0.91, 95% CI 0.80-1.00), with sensitivity 76.5%, specificity 96.6%, positive predictive value 92.9%, and negative predictive value 87.5%. In serum biomarker analysis, patients with AF had significantly higher levels of C-terminal telopeptide of type I collagen (CITP) than those without AF (P=0.009). Follow-up data were available for 45 patients (97.8%), with a median follow-up duration of 9.2 months (IQR, 7.7-12.2 months). Conclusions In patients with DMR, AF was associated with more advanced LA structural remodeling, impaired LA function, and higher CMR LGE burden. Echocardiographic LA functional parameters, when combined with LALGE measures, may provide complementary information for the discrimination of AF. Given the exploratory nature of this study, the findings require external validation.

Background: Iatrogenic atrial septal defect (iASD) is a known consequence of transseptal catheterization. Left atrial intracardiac echocardiography (LA ICE) requires additional septal instrumentation, yet data on persistent iASD after pulsed field ablation (PFA) with an LA ICE workflow remain limited. We evaluated the incidence, predictors, and one-year clinical significance of persistent iASD in this setting. Methods: Consecutive patients undergoing PFA for atrial fibrillation with LA ICE were prospectively evaluated with transthoracic echocardiography before ablation and at one year, including systematic agitated saline contrast. Persistent iASD was defined as residual interatrial shunting on color Doppler at follow-up, classified as small (<3 mm), moderate (3-5 mm), or large (>5 mm). Groups were compared by t-test and chi-square test. Results: Among 850 patients, persistent iASD was identified in 153 (18.0%) at one year; 97 (63.4%) were small and 56 (36.6%) moderate, with no large defects. All shunts were left-to-right. No stroke or transient ischemic attack, paradoxical embolism, hypoxemia, right-heart enlargement, or septal closure occurred. Persistent iASD was associated with female sex (64.7% vs 48.1%), longer septal dwell time (52{+/-}12 vs 31{+/-}11 min), higher left atrial pressure (28{+/-}4 vs 12{+/-}3 mmHg), lower LVEF (32{+/-}11% vs 54{+/-}14%), and larger-caliber sheaths ([&ge;]17 Fr; 80.4% vs 48.2%; all p<0.001). Conclusions: Persistent iASD following PFA with LA ICE occurs in approximately one in five patients but is predominantly small, exclusively left-to-right, and clinically benign at one year. Persistence is associated with mechanical and hemodynamic factors, particularly sheath caliber, rather than the ablation energy source.

Aims Polymer-free drug-eluting stents were developed to enhance vascular biocompatibility and safety while maintaining antirestenotic efficacy. The TRANSEVER registry evaluated 12-month clinical outcomes of the polymer-free everolimus-eluting ISAR SUMMIT stent in a large, real-world population undergoing percutaneous coronary intervention. Methods This prospective, multicentre study enrolled patients with coronary artery disease undergoing PCI with the ISAR SUMMIT stent across 33 centres in India. The primary endpoint was target-lesion failure (TLF) at 12 months, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularisation. Secondary endpoints included the patient-oriented composite endpoint (POCE) of all-cause death, any myocardial infarction, stroke, revascularization, and definite/probable stent thrombosis. Results A total of 1,000 patients were enrolled, of whom 996 completed 12-month follow-up. The cohort presented with a high-risk profile, including an acute coronary syndrome (ACS) in 89.8% of the cases and diabetes mellitus in 44.4% of them. Procedural outcomes were excellent in terms of device success and final TIMI 3 flow (achieved in all treated lesions). At 12 months, TLF occurred in 15 patients (1.5%). Definite or probable stent thrombosis was observed in 8 patients (0.8%). POCE was observed in only 21 patients (2.1%). Conclusions In this large, contemporary real-world population with a very high proportion of patients presenting with ACS, the polymer-free everolimus-eluting ISAR SUMMIT stent demonstrated favourable 12-month clinical outcomes, with low rates of target lesion failure and stent thrombosis. These results suggest that this novel device is both safe and effective for routine clinical use.

Background Exercise intolerance is common in adults with repaired tetralogy of Fallot (rTOF) despite preserved left ventricular ejection fraction (LVEF [&ge;]50%). Whether reduced exercise capacity is associated with early cardiac remodeling remains unclear. Objectives To determine whether reduced exercise capacity in rTOF with preserved LVEF is associated with diastolic dysfunction, atrial remodeling, right ventricular (RV) dysfunction, and myocardial fibrosis. Methods We retrospectively studied adults with rTOF and preserved LVEF who underwent cardiopulmonary exercise testing (CPET) and transthoracic echocardiography (TTE) and/or cardiac MRI (CMR) within 18 months. Exercise capacity was assessed by percent-predicted peak VO2 (ppVO2). Diastolic function and atrial remodeling were evaluated by TTE, and CMR assessed RV function and myocardial fibrosis. Results Reduced exercise capacity was associated with larger left atrial volume index (LAVI; p < 0.001), elevated E/e' and reduced e' velocity (both p < 0.05), and reduced RV systolic function (p < 0.001). LAVI correlated inversely with ppVO2 ({rho} = -0.27, p = 0.003). A composite diastolic dysfunction score showed a graded relationship with exercise capacity, with patients exhibiting [&ge;]2 abnormalities having lower ppVO2 than those with [&le;]1 abnormality (both p < 0.01). In contrast, pulmonary regurgitation (PR) severity and myocardial fibrosis by late gadolinium enhancement (LGE) were not associated with exercise capacity. Conclusions In adults with rTOF and preserved LVEF, reduced exercise capacity is associated with atrial remodeling, diastolic dysfunction, and RV dysfunction despite the absence of overt myocardial fibrosis. This suggests that multimodal imaging identifies an imaging-defined cardiac remodeling phenotype associated with early functional impairment.

Background Adults with a systemic right ventricle (sRV) due to congenitally corrected transposition of the great arteries (ccTGA) or atrial switch repair for d-transposition of the great arteries (d-TGA) experience substantial physiologic and psychosocial morbidity. Relationships among exercise capacity, sRV function, and mental health remain incompletely characterized. Objectives To characterize relationships among anatomic subtype, exercise capacity, sRV function, and mental health in adults with sRV physiology. Methods We performed a retrospective cohort study of adults with ccTGA or d-TGA (Mustard/Senning) followed at a tertiary Adult Congenital Heart Disease program from 2000 to 2025. Clinical, imaging, cardiopulmonary exercise testing, and patient-reported data were obtained from electronic health records. Mental health diagnoses were identified from clinical documentation. Functional status was assessed using NYHA class and the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Results Among 137 adults (ccTGA, n = 51; d-TGA, n = 86), percent-predicted peak VO2 was lower in d-TGA than ccTGA (60% vs 74%, p < 0.001), as was sRV systolic function (41 +/- 11% vs 47 +/- 10%, p < 0.01). Anxiety or depression was more common in d-TGA (46% vs 25%, p < 0.05). Across the cohort, anxiety or depression was associated with lower exercise capacity, worse NYHA functional class, and lower KCCQ scores. Conclusions Adults with d-TGA following atrial switch have lower exercise capacity, reduced sRV systolic function, and greater mental health burden than adults with ccTGA. These findings support integrated assessment of physiologic performance, functional status, and mental health in adults with sRV physiology.

Background: High-sensitivity cardiac troponin (hs-cTn) assays enable safe early discharge of patients at very low risk for myocardial infarction. We previously developed a single-sample rule-out pathway using the ARCHITECT hs-cTnI assay to risk stratify patients with suspected acute coronary syndrome. In a secondary analysis of the POC-ET (Point of Care Evaluation of High-sensitivity Cardiac Troponin) study, we evaluated performance of risk stratification with the Alinity hs-cTnI assay. Methods: Patients presenting with possible myocardial infarction in the POC-ET (NCT05665127) study were included. The primary outcome was type 1, 4b or 4c myocardial infarction or cardiac death at 30 days. Cardiac troponin I (cTnI) was measured in stored materials using the ARCHITECT and Alinity hs-cTnI assays. The sex-specific 99th percentile upper reference limit (URL) are 34 ng/L in men and 16 ng/L in women for both assays. Agreement was assessed with Bland-and-Altman limit of agreement method, Passing Bablok regression, and Pearson's correlation coefficient. Distributions of presentation measurements were compared with Kolmogorov-Smirnov test. Performance was evaluated in the overall population and prespecified subgroups. The negative predictive value (NPV) and sensitivity were determined and proportion of patients identified as low, intermediate, and high risk were calculated and modelled using ordinal logistic regression. Results: In 986 patients (60 [51-70] years, 38% female), 78 (7.9%) had a primary outcome. Strong agreement was found in the raw cTnI measurements (99% samples within the Bland-Altman limit of agreement; correlation coefficient r: 0.967 (95% CI 0.964-0.969, P<0.001); Passing Bablok regression: slope 1.12 [1.11-1.13], intercept -0.16 [-0.18 to -0.13]). At presentation, distributions of cTnI measurements by the two assays were similar (P=0.810). Both assays showed comparable diagnostic performance using a risk stratification threshold of <5 ng/L and the sex-specific diagnostic threshold, with the same NPV (Alinity 100 [99.7-100]% versus ARCHITECT 100 [99.7-100]%) and sensitivity (Alinity 100 [97.3-100]% versus ARCHITECT 100 [97.3-100]%). Similar proportions of patients stratified as low- (Alinity 67% versus ARCHITECT 67%), intermediate-risk (23% versus 24%) and high-risk (10% versus 9%) at presentation with minor reclassification. Similar efficacy was observed across subgroups stratified by sex, age, history of myocardial infarction, renal function, and symptom duration. Conclusions: The Alinity hs-cTnI and the ARCHITECT hs-cTnI assays can be used interchangeably in the assessment of suspected myocardial infarction with comparable safety and efficacy.

Background: Apical sparing of left ventricular longitudinal strain (LS) is an echocardiographic clue to cardiac amyloidosis but may also occur in hypertensive heart disease (HHD). Objectives: To determine whether apical sparing in HHD is associated with regional left ventricular wall stress estimated according to Laplace's law. Methods: We retrospectively studied 1,559 patients with HHD, 47 with light-chain cardiac amyloidosis (ALCA), and 409 normotensive controls. Artificial intelligence-assisted echocardiography quantified segmental LS, wall thickness, and cavity radius at the basal, midventricular, and apical levels. Wall stress was estimated as mean blood pressure (MBP) x radius/(2 x wall thickness). Apical sparing was defined as a relative regional strain ratio (RRSR)[&ge;]1.0. Results: Apical sparing was present in 14 patients with HHD (0.9%), 13 with ALCA (27.7%), and no controls. Among HHD patients with apical sparing, RRSR decreased from 1.11{+/-}0.13 to 0.72{+/-}0.10 after antihypertensive treatment (P<0.001), accompanied by reduced wall stress and improved basal and midventricular LS, with resolution of apical sparing in all 14 patients. In the overall HHD cohort, changes in MBP and left ventricular mass index were independently associated with changes in RRSR. In an exploratory analysis of HHD patients with apical sparing, a reduction in basal wall stress was associated with a reduction in RRSR ({beta}=0.267 for {bigtriangleup}RRSRx100, 95% CI 0.023-0.511; P=0.036). In ALCA, favorable hematologic response was the only determinant of RRSR reduction. Conclusions: Apical sparing in HHD was uncommon but reversible and may represent a load-sensitive deformation pattern associated with regional wall stress, consistent with Laplace's law.

Aims: Prognostic stratification and individual management are essential in the heterogeneous population of non-ischemic dilated cardiomyopathy (NIDCM). We applied unsupervised machine learning (ML) clustering in NIDCM cohorts, using semi-automated artificial intelligence (AI)-based cardiac magnetic resonance imaging (CMR) measurements with multimodal data to identify distinct phenotypes, characterize echocardiographic remodeling trajectories, and evaluate prognostic significance. Methods and results: We analyzed 347 patients with NIDCM from two tertiary centers who underwent CMR and echocardiography at baseline, with follow-up echocardiography at a median 12 months. The cohort was randomly divided into derivation (n=242) and validation (n=105) sets using stratification by the composite outcome. Remodeling trajectories were evaluated using follow-up echocardiographic changes, and associations with outcomes were assessed by multivariable Cox regression adjusted for age and sex. Using eleven comprehensive clinical, laboratory, echocardiographic, and CMR-derived variables, partitioning around medoids clustering identified three phenotypes: (i) a younger, male-predominant preserved phenotype; (ii) a metabolic, fibrotic-remodeling phenotype; and (iii) an atrial fibrillation-predominant biventricular dysfunction phenotype. Cluster 1 showed the most favorable prognosis, whereas Cluster 3 had the highest risk of the composite outcome. Although LV reverse remodeling occurred across all clusters, Cluster 3 was characterized by attenuated LA reverse remodeling, suggesting persistent LA dysfunction. Conclusion: Unsupervised ML-based clustering of NIDCM patients, integrating AI-derived CMR parameters with multimodal data, identified three clusters exhibiting distinct patterns in longitudinal echocardiographic trajectories and outcomes. This strategy may enable more individualized management in heterogeneous NIDCM.

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome, and patients with a small left ventricular (LV) volume phenotype exhibit greater preload dependency. Whether the association between persistent outpatient oral loop diuretic use and clinical outcomes differs by LV volume phenotype remains unclear. Methods: We conducted a retrospective single-center cohort study of consecutive patients with heart failure and an LV ejection fraction [&ge;]50% who underwent transthoracic echocardiography between 2009 and 2024. Patients were stratified by LV volume phenotype using sex-specific LV end-diastolic volume index cutoffs. Associations between outpatient oral loop diuretic use and HF hospitalization, worsening renal function, and all-cause death were evaluated using multivariable time-varying Cox proportional hazards models, including interaction testing by LV phenotype. Results: Among 12,748 eligible patients, 1,437 had a small LV phenotype and 11,311 had a normal LV phenotype. Patients with a small LV phenotype initiated outpatient oral loop diuretics earlier and more frequently than those with a normal LV phenotype, while maintenance doses were comparable between groups. Outpatient oral loop diuretic use was associated with HF hospitalization in both phenotypes, with a significantly stronger association in the small LV group (hazard ratio [HR], 2.52; 95% confidence interval [CI], 1.68-3.78) than in the normal LV group (HR, 2.10; 95% CI, 1.77-2.49; P for interaction = 0.001). No significant interaction by LV phenotype was observed for worsening renal function or all-cause death. Fine-Gray competing-risk analyses showed a consistent interaction pattern. Conclusions: Persistent outpatient oral loop diuretic use was more strongly associated with HF hospitalization in patients with a small LV phenotype than in those with a normal LV phenotype. LV volume phenotype may help identify patients who warrant closer monitoring and more individualized diuretic management.

Background: Postoperative atrial fibrillation (POAF) is a frequent complication following coronary artery bypass grafting (CABG) and is associated with increased acute morbidity and resource utilization. However, its independent role in driving post-discharge adverse events in contemporary practice remains debated. Objective: To evaluate the association between POAF and short-term outcomes after CABG, and to utilize empirical Bayesian risk updating to stratify 90-day post-discharge vulnerabilities. Methods: A retrospective cohort analysis of 4,684 adult patients who underwent isolated CABG in Florida between January 1, 2021, and June 30, 2024, was conducted, excluding those with documented preoperative AFib. We employed multivariable negative binomial and logistic regression models to assess length of stay (LOS), discharge disposition, 90-day readmission, and 90-day composite complications. Additionally, a Bayesian Beta-Binomial conjugate model with an objective Jeffreys Prior was utilized to estimate the posterior probabilities of adverse outcomes across key clinical phenotypes. Results: POAF occurred in 355 patients (7.58%). Multivariable analysis demonstrated a 30% relative increase in expected LOS (IRR 1.30, 95% CI [1.23 - 1.36], P < .001) and 33% higher odds of facility discharge (OR 1.33, 95% CI [1.03 - 1.72], P = .030) for patients with POAF. However, POAF was not independently associated with 90-day readmission (OR 1.25, P = .063) or composite complications (OR 1.20, P = .118). Chronic heart failure (CHF) emerged as the dominant predictor. Bayesian risk updating revealed that while the baseline posterior probability for a 90-day complication was 27.2%, the synergistic presence of both POAF and CHF radically shifted this posterior risk to 42.6% (Probability of Direction > 0.999 vs. baseline). Conclusions: POAF prolongs hospitalization and drives non-home discharges, but it does not independently dictate 90-day morbidity. Bayesian stratification demonstrates that post-discharge outcomes are predominantly driven by underlying chronic conditions. Effective reduction of readmissions requires robust transition-of-care frameworks, empowering primary care clinicians to aggressively optimize heart failure and metabolic disease rather than focusing solely on the acute surgical arrhythmic event.

Background Totally endoscopic aortic root (AR) surgery via right anterior minithoracotomy (RAMT) may reduce surgical trauma and accelerate recovery compared with full sternotomy (FS). However, the approach is technically demanding due to limited access and anatomical complexity. This study compares early clinical outcomes and quality of life (QoL) after RAMT versus FS to evaluate the feasibility and safety of the totally endoscopic approach. Methods This single-center, retrospective study included 149 patients underwent AR surgery via RAMT (n=74) or FS (n=75) between January 2021 and March 2026. Patients with aortic dissection, infective endocarditis, redo surgery, concomitant procedures, or arch replacement were excluded. Operative outcomes, postoperative recovery, 30-day and 1-year mortality were analyzed. QoL was assessed using the Short Form-8 (SF-8) questionnaire. Results The median age was 60.0 years, and 79.9% of patients were male. Bentall procedure was performed in 84.6% of patients, 15.4% underwent a David procedure. Compared with FS-AR, RAMT-AR was associated with shorter median operative time (147.0 vs. 178.0 min; p<0.001), lower median chest drainage volume (650.0 vs. 850.0 mL; p<0.001), and shorter median ICU stay (24.0 vs. 25.0 h; p=0.008) and hospital stay (6.0 vs. 8.0 days; p=0.028). Overall, 30-day and 1-year mortality was 0.7%. SF-8 analysis demonstrated significantly higher physical and mental component scores in RAMT-AR patients. Conclusion In specialized centers, totally endoscopic AR surgery via RAMT is a safe and feasible minimally invasive approach associated with favorable early outcomes and a potential benefit in postoperative physical and mental QoL by reducing surgical trauma.

Background: ST-elevation myocardial infarction (STEMI) remains a major cause of global mortality. While troponin is the gold-standard biomarker for myocardial injury, a subset of patients presents with troponin levels below the clinical "rule-in" threshold upon hospital admission. The long-term prognostic significance of these initial "low-troponin" presentations in a large-scale population remains insufficiently characterized. Methods: We conducted a retrospective multicenter cohort study using the "KINERET" database, analyzing 8,394 patients diagnosed with STEMI who underwent percutaneous coronary intervention (PCI) at four academic medical centers in Israel between 2016 and 2023. Patients were stratified into two groups based on ESC rule-in criteria for high-sensitivity cardiac troponin (hs-cTn) at admission: a High trop group (above rule-in cutoff) and a Low trop group (below rule-in cutoff). The primary outcome was all-cause mortality at 5 years. Results: Of the 8,394 patients (mean age 68.3{+/-}13.3 years; 76% male), 36.5% (n=3,064) presented with troponin levels below the rule-in cutoff. Patients in the High trop group were older and had a higher prevalence of comorbidities, including heart failure (46.7% vs. 28.7%) and chronic kidney disease (13.9% vs. 9%). The Low trop group demonstrated significantly higher survival rates at both 1 year (92.9% vs. 84.0%, p<0.001) and 5 years (85.7% vs. 75.0%, p<0.001). After adjusting for age, sex, and comorbidities in a multivariate Cox regression model, initially elevated troponin remained a robust independent predictor of 5-year mortality (HR 1.15, 95% CI 1.14-1.16, p<0.001), alongside age >75, female sex, and chronic kidney disease. Conclusions: STEMI patients presenting with initial troponin levels below the diagnostic rule-in threshold have a significantly better short- and long-term prognosis compared to those with early troponin elevation. Moreover, admission troponin levels serve as a powerful predictor of 5-year mortality and may be used as an independent prognostic factor following STEMI.

BACKGROUND: Chronic coronary syndromes (CCS) remain under-characterized in Latin America, where clinical profiles may differ from high-income countries. OBJECTIVE: We aim to characterize the clinical presentation, coronary anatomic profile, and pharmacologic treatment patterns of adults living with CCS using data from the Mexican Chronic Coronary Syndrome Registry (RESINCCRO). METHODS: RESINCCRO is an observational, multicenter, cross-sectional registry conducted across ~50 centers in five regions from Mexico. We included adults ([&ge;]18 years) enrolled between September 2024 and March 2025 who met 2019 ESC CCS criteria. Coronary imaging data was collected from medical records into a standardized electronic case report form. RESULTS: We enrolled 3,029 adults (men [72.5%]; mean age 67.2 {+/-} 10.7 years). Cardiometabolic comorbidities were frequent: overweight/obesity (76%), arterial hypertension (69.0%), type 2 diabetes (44.0%), and chronic kidney disease (24.2%). Persistent angina/equivalents occurred in (23.9%), of which most had Canadian Cardiovascular Society class I - II (91.2%). The mean LVEF was of 53.7 {+/-} 12.0. Cardiac rehabilitation participation was (6.2%). Median LDL-C was 70 mg/dL (IQR 51 - 95) and LDL <55 mg/dL was only 26.1%, despite high prescription of lipid-lowering therapies, including statins (93.2%), ezetimibe (24.6%), and PCSK9 inhibitors (2.4%). 60.3% had obstructive epicardial disease. CONCLUSIONS: Mexican adults with CCS exhibit high cardiometabolic burden, frequent symptoms, suboptimal LDL-C goal attainment, low rehabilitation uptake, and a substantial obstructive phenotype. These findings highlight opportunities to intensify secondary prevention, adopt mechanism-directed evaluation and therapy, and expand cardiac rehabilitation to improve CCS care in Mexico.

Background: Although prophylactic veno-arterial extracorporeal membrane oxygenation (VA-ECMO) may provide hemodynamic stability during high-risk percutaneous coronary intervention (PCI), it is also associated with potential complications and may not be necessary in most cases. In this context, we proposed a pre-cannulated standby ECMO strategy and designed the ECMO-READY trial to evaluate the comparative effectiveness of pre-cannulated standby versus prophylactic ECMO strategies in patients undergoing high-risk PCI. Methods: The ECMO-READY trial is a prospective, multicenter, open-label, randomized controlled trial conducted in 8 sites in China. A total of 176 patients scheduled to undergo high-risk PCI will be randomly assigned in a 1:1 ratio to either a pre-cannulated standby ECMO strategy or a prophylactic ECMO strategy. The primary outcome is the 30-day incidence of major adverse events, including death, myocardial, infarction, repeat revascularization, stroke, PCI failure, limb ischemia, major bleeding, vascular injury requiring intervention, and need for renal replacement therapy. Secondary outcomes include post-procedural hemoglobin decline, post-procedural platelet count decline, red blood cell transfusion rate, peak post-procedural interleukin-6 level, use of intra-aortic balloon pump, duration of ECMO support, length of hospital stay, hospitalization cost, and each component of the composite primary outcome. Enrollment began in March 2025 and is anticipated to be completed by December 2026. Discussion: The ECMO-READY trial will provide prospective randomized evidence regarding ECMO support strategies in patients undergoing high-risk PCI and may help inform future clinical practice. Trial registration: ClinicalTrials.gov NCT06274411. Registered on February 23, 2024. Keywords Percutaneous coronary intervention, High-risk, Extracorporeal membrane oxygenation, Ready, Standby, prophylactic, Major adverse events

Background: Aspirin-free P2Y12-inhibitor monotherapy after percutaneous coronary intervention (PCI) is an alternative to dual antiplatelet therapy (DAPT), but the evidence rests largely on full-dose ticagrelor in acute coronary syndrome and on designs retaining a DAPT run-in; East-Asian patients may not require the same antithrombotic intensity. We compared standard DAPT, DAPT with half-dose ticagrelor, and aspirin-free half-dose ticagrelor monotherapy initiated on the day of PCI in chronic coronary syndrome (CCS). Methods: Sixty-one East-Asian patients with CCS scheduled for elective PCI were randomized 1:1:1 to Control (aspirin plus clopidogrel), Experimental A (aspirin plus ticagrelor 45 mg twice daily), or Experimental B (ticagrelor 45 mg monotherapy, aspirin discontinued at day 2). DAPT arms continued for six months; Experimental B continued indefinitely. P2Y12 reaction units (PRU) were measured at baseline and at a median of 17 days. Results: PRU reduction was three-fold greater in both ticagrelor arms than in Control ({Delta}PRU -188 and -181 versus -60.5; P<0.001), with no difference between ticagrelor arms (P=0.772). At 12 months, major adverse cardiovascular events (MACE) and clinically relevant bleeding each occurred in 1 of 17 Experimental B patients (5.9%) and in neither other arm. One Experimental A patient crossed over for ticagrelor-induced dyspnea; no stent thrombosis or cardiac death occurred. Conclusions: In East-Asian patients with CCS, half-dose ticagrelor produced markedly greater platelet inhibition than standard DAPT, with an identical effect whether given with or without aspirin. It merits evaluation in an adequately powered randomized trial. Clinical Trial Registration. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT07622056

Background: A growing burden of cardiovascular risk factors has raised cardiovascular disease-related mortality in Sub-Saharan Africa (SSA), driving higher prevalence of heart failure with reduced ejection fraction (HFrEF) and its complication with atrial fibrillation (AF). No prospective study has examined AF's clinical impact on HFrEF in SSA. Aim: To determine AF prevalence in HFrEF, describe HFrEF-AF clinical characteristics, and determine AF's impact on mortality. Methods: In this prospective observational study at a tertiary hospital in Johannesburg, 136 HFrEF patients were enrolled and categorised as HFrEF- SR (sinus rhythm) or HFrEF-AF. Baseline clinical characteristics and biochemistry were recorded. Comprehensive echocardiography including left atrial strain by 2D speckle-tracking was performed. Median follow-up was 30.6 months. Results: AF was present in 28 patients (21%). The mean age was 58.7 {+/-} 14.9 years (52.9% male) and differed between groups (p < 0.001). Hypertensive heart disease was the leading cause of HFrEF (36%). Compared with SR, HFrEF-AF patients had poorer health status (KCCQ 27 [16-43] vs 45 [32-60], p < 0.001) and lower left atrial strain (26.2 {+/-} 11.3%, p < 0.001). Guideline-directed medical therapy was suboptimal in the AF group: anticoagulation use was higher than SR (60% vs 9.5%, p < 0.001) but overall inadequate; HFrEF-AF patients received lower median doses of carvedilol (15.6 mg vs 25 mg, p = 0.002) and enalapril (10 mg vs 20 mg, p = 0.004), and fewer received spironolactone (50% vs 75.3%, p = 0.013). Survival was significantly lower in HFrEF-AF (0.41 [0.22-0.61]) versus SR (0.73 [0.61-0.82], p < 0.001). Independent predictors of mortality included prior stroke, lower TAPSE and KCCQ, and higher E/e' and heart rate. Conclusion: AF is common among HFrEF patients in this SSA cohort (though lower than in high-income countries) and associates with worse clinical status, suboptimal therapy, and higher mortality.

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. Durable mitral isthmus (MI) block remains challenging in persistent atrial fibrillation (PeAF) ablation. Recent epicardial vein of Marshall (VoM) recordings have shown incomplete MI transmurality and time-dependent conduction recovery after pulsed field ablation (PFA). Whether systematic VoM ethanol infusion (VoM-EI) followed by focal PFA provides stable acute MI block remains unknown. **Objectives.** To assess the incidence, timing, and procedural implications of early MI conduction recovery after systematic VoM-EI followed by focal Sphere-9 PFA. Methods.In this prospective single-center study, 55 consecutive patients undergoing first ablation for symptomatic PeAF with planned MI ablation were screened. VoM-EI was systematically attempted before left atrial access and successfully performed in 51 (92.7%), who constituted the study cohort. Pulmonary vein isolation, roof-line, and MI ablation were performed with the Sphere-9? lattice-tip catheter. After bidirectional MI block, conduction was systematically reassessed during a standardized 30-minute waiting period. Results.Mean age was 70.3 {+/-} 8.2 years, and 36 patients (70.6%) were men. Initial bidirectional MI block was achieved in 50/51 patients (98.0%). During the waiting period, conduction recovered in 9/50 (18.0%; 95% CI, 9.8%-30.8%), at a median of 16 minutes (IQR, 10-20; range, 8?23). Six of 9 patients with recovery (66.7%) required targeted coronary sinus (CS) ablation. Block was restored in all 9, yielding a final block rate of 50/51 (98.0%). Median procedure duration was 82 minutes (IQR, 73-95), with no major complications. Conclusions. Immediate bidirectional MI block was not synonymous with stable block. Despite systematic VoM-EI followed by focal Sphere-9 PFA, conduction recovered in approximately one in five patients, including beyond 20 minutes, and two thirds required targeted CS ablation. These findings support standardized 30-minute reassessment and targeted CS interrogation rather than reliance on immediate block. Chronic invasive remapping is required to determine whether this strategy improves long-term MI block durability.

Background: Clinical outcomes of switching versus continuing direct oral anticoagulant (DOAC) among atrial fibrillation (AF) patients who experienced an ischemic stroke despite receiving DOAC therapy are uncertain. Methods: We included patients with AF who were hospitalized for ischemic stroke (index stroke) between January 1, 2016, and June 30, 2022, while receiving DOAC therapy and who resumed DOAC within 90 days after discharge in the Merative MarketScan Commercial and Medicare databases. Patients were classified as DOAC-switched or DOAC-continued according to whether the DOAC agent changed or remained the same after the index stroke; secondary analyses considered individual DOACs. The primary outcome was recurrent ischemic stroke; secondary outcomes included major bleeding and a composite outcome (bleeding or ischemic stroke). Propensity score-based overlap weighting and weighted Cox models were used to estimate adjusted hazard ratios (aHRs). Results: A total of 1175 patients were eligible for the study, of whom 970 (82.6%) continued and 205 (17.4%) switched DOAC therapy. Comparing DOAC-switched to DOAC-continued was not significantly associated with recurrent ischemic stroke (aHR, 1.20; 95% CI, 0.63-2.30), major bleeding (aHR, 0.60; 95% CI, 0.21-1.72), or the composite outcome (aHR, 0.98; 95% CI, 0.56-1.70). However, among patients who received apixaban before stroke, switching to rivaroxaban was associated with a higher risk of recurrent ischemic stroke (aHR, 2.70; 95% CI, 1.05-6.95). Conclusions: Overall, switching DOAC therapy after ischemic stroke was not associated with improved clinical outcomes. Switching from apixaban to rivaroxaban, however, could increase risk of recurrent ischemic stroke.

Background: Aortic stenosis (AS) is a progressive valvular disease associated with poor prognosis once symptoms develop, yet routine echocardiographic screening is impractical. While artificial intelligence (AI)-based electrocardiogram (ECG) models have shown promise for AS detection, it remains unclear whether they primarily reflect conventional left ventricular hypertrophy (LVH) voltage criteria or capture additional ECG features. Methods and Results: We developed a deep learning model using 244,816 ECGs from 51,713 patients across six academic institutions in Japan (CLIDAS database). AS labels were derived from inpatient Diagnosis Procedure Combination (DPC) codes. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.849 (95% confidence interval 0.832-0.865) in the independent test cohort, with consistent performance across institutions, sex, and age. At a threshold of 0.1, sensitivity was 79.1%, specificity was 73.9%, and negative predictive value (NPV) was 98.0%. Conventional LVH voltage criteria (Sokolow-Lyon AUC 0.706; Cornell AUC 0.692) showed lower performance, and adding them to the AI model conferred no incremental benefit (AUC 0.849 vs. 0.847). Gradient-weighted class activation mapping (Grad-CAM) revealed predominant attention around QRS complexes in limb leads, beyond regions typically assessed in LVH evaluation. Conclusions: This multicenter AI-ECG model demonstrated strong discrimination for AS and captured ECG features beyond conventional LVH voltage criteria. The high NPV supports its use as a rule-out pre-screening tool.