International Journal of Cardiology

BackgroundAcute type A aortic dissection (AAAD) complicated by cardiopulmonary arrest is characterized by high mortality rates, rendering the selection of surgical candidates a subject of intense debate. Despite the necessity for cardiopulmonary resuscitation (CPR) prior to the completion of a definitive intervention, the prognostic impact of CPR duration on postoperative survival and neurological outcomes remains insufficiently elucidated. This study sought to evaluate the association between pre- and intra-operative CPR duration and the incidence of early mortality and central nervous system (CNS) complications in patients undergoing emergent surgical repair for AAAD. MethodsThis retrospective, cohort study was conducted at two tertiary community hospitals in Japan. All the patients who underwent emergency surgery for AAAD between January 2014 and December 2024 were enrolled. A multilevel Cox proportional hazards model, with each patient as level 1 and institutions as level 2, was used to evaluate the association between pre-or intra-operative CPR events and early postoperative mortality and CNS complications. ResultsOf the 880 patients enrolled, 785 (89.2%), 13 (1.5%), and 82 (9.3%) were without CPR, with CPR <15 min, and with CPR [&ge;]15 min, respectively. Among them, death within 30 days post-surgery occurred in 76/785 (9.7%), 3/13 (23.1%), and 47/82 (57.3%), respectively. CNS complications within 30 days post-surgery occurred in 141/785 (18.0%), 5/13 (38.5%), and 38/82 (46.3%) without CPR, CPR <15 min, and [&ge;]15 min, respectively. In multivariable analysis, CPR lasting [&ge;]15 min was associated with mortality within 30 days post-surgery (adjusted hazard ratio, 7.66; 95% confidence interval [CI], 3.56-16.5; P<0.001). Both CPR <15 min and [&ge;]15 min were associated with an increase in the sub-hazard ratio of CNS complications within 30 days post-surgery (adjusted sub-hazard ratios, 4.49; 95% CI, 3.92-5.11; P<0.001, and 3.62; 95% CI, 2.73-4.81; P<0.001, respectively). ConclusionA preoperative CPR duration of [&ge;]15 min prior to the initiation of cardiopulmonary bypass or extracorporeal membrane oxygenation was associated with a substantial escalation in 30-day mortality compared with patients without CPR. These findings suggest that CPR duration might serve as a pivotal prognostic indicator, necessitating careful consideration for surgical indication in patients with AAAD complicated by CPR. CLINICAL PERSPECTIVEO_ST_ABSWhat is new?C_ST_ABSO_LIPre- or intra-operative cardiopulmonary resuscitation lasting [&ge;]15 min in patients with acute type A dissection is associated with a nearly seven-fold increase in 30-day postoperative mortality. C_LIO_LIBoth short (<15 min) and prolonged ([&ge;]15 min) cardiopulmonary resuscitation are associated with a higher risk of early postoperative complications in the central nervous system. C_LI What are the clinical implications?O_LIPatients with acute type A dissection who require pre- or intra-operative cardiopulmonary resuscitation [&ge;]15 min should undergo careful multidisciplinary evaluation, as the risk of early mortality is substantially elevated. C_LIO_LIEven brief cardiopulmonary resuscitation is associated with increased neurological complications, highlighting the need for early neurological monitoring and supportive care postoperatively. C_LI

Background: Primary graft dysfunction (PGD) remains one of the leading causes of early mortality after pediatric heart transplant (HT). While neurodevelopmental impacts of congenital heart disease (CHD) are well-characterized, the effect of PGD on long-term neurodevelopmental outcomes in pediatric HT recipients remains unknown. We sought to determine the association between PGD and neurodevelopmental outcomes in this population. Methods: We performed a retrospective cohort study using the United Network for Organ Sharing (UNOS) database. All pediatric (age <18 years) isolated heart transplant recipients from 2010-2025 were included. The most recent pre- and post-transplant neurodevelopmental outcomes including cognitive delay, motor development, academic progress, and function status (stratified by age) were compared between PGD (n=434) and non- PGD groups (n=6956). Results: PGD patients had significantly worse pre-transplant functional status and motor development. Post-transplant, PGD was associated with worse motor development (18.8% vs. 13.0% definite motor delay; p=0.01) and functional status in younger children (39.5% vs. 57.8% able to keep up with peers; p<0.001). Post-transplant stroke occurred 3.5 times more frequently in PGD patients (11.5% vs. 3.3%; p<0.001). Cognitive development (p=0.94) and academic progress (p=0.096) did not differ significantly. Thirty-day (7.8% vs. 1.9%) and 1-year mortality (20.3% vs. 6.4%) were significantly higher in PGD patients (both p<0.001). Conclusions: This is the first study to characterize neurodevelopmental outcomes in pediatric patients undergoing HT with PGD. PGD is associated with significantly worse motor development and functional status independent of pre-transplant baseline. There is a 3.5-fold higher stroke rate providing a plausible neurological mechanism. The findings support targeted developmental surveillance recommendations and early intervention for this high-risk population.

BackgroundIron metabolism disorder is highly prevalent before and after heart transplantation (HTx). The impact of pretransplant and posttransplant iron disorder on posttransplant outcomes is unclear. ObjectivePretransplant serum levels of key regulator proteins of iron metabolism (hepcidin, interleukin-6, erythroferrone) were tested for prediction of the composite outcome 1-year posttransplant all-cause mortality (ACM) or [&ge;]moderate acute cellular rejection (ACR). Furthermore, serum levels of these proteins were measured at 1-year posttransplant to explore their posttransplant course and association with ACR. ResultsIn a multicenter cohort including 276 consecutive HTx recipients, patients with or without outcome (n=118/158, respectively) did not differ for pretransplant demographics, mismatch of donor/recipient sex, mismatch of HLA epitopes, and hepcidin or interleukin-6 levels. However, pretransplant erythroferrone levels were higher (1.40 vs. 1.19 ng/mL; p=0.013) and hemoglobin levels were lower (124.5 vs. 127 g/L; p=0.004) among patients with the composite outcome. Pretransplant erythroferrone levels >2.25 ng/ml (4th-quartile) were significantly associated with the composite outcome in multivariable analysis (OR 2.17; 95% CI 1.19-3.94, p=0.011; reference: 1st-3rd quartiles). In adjusted predicted proportions analysis, the incidence of the composite outcome was higher in 4th-quartile patients when compared to 1-3rd -quartiles patients (58.0 vs. 37.7%; p=0.003). At 1-year posttransplant, 80.4% of patients with pretransplant erythroferrone levels >2.25 ng/ml remained high; 88.4% of patients with pretransplant erythroferrone levels [&le;]2.25 ng/ml had high levels posttransplant. In 1-year survivors with high erythroferrone levels and [&ge;]moderate ACR during the first postoperative year, the ratio of the opponent regulators of hepcidin gene expression, erythroferrone to interleukin-6, was higher when compared to those without ACR (1.18 vs. 0.41; p=0.016). Hepcidin levels were not different between these two subgroups indicating disproportionate ERFE increase. ConclusionHigh pretransplant erythroferrone levels predict the composite posttransplant outcome 1-year ACM and ACR. Disproportionately high posttransplant erythroferrone levels are related with [&ge;]moderate acute cellular rejection.

ObjectiveTo analyze the experience of the last six years with ECMO in Uncontrolled Donation after Circulatory Death (uDCD), assessing the clinical and logistical factors that determine donation effectiveness and the viability of retrieved organs, with the nurse perfusionist as the central figure in organ perfusion. MethodsRetrospective observational study of uDCD procedures performed at Hospital Clinic de Barcelona between June 2019 and October 2025. ResultsOf 184 out-of-hospital ECMO-CPR activations, 108 (58.7%) underwent perfusion; 72 donor cases (66.7%) were generated, and 109 kidneys (75.7%) and 3 livers (4.15%) were retrieved. The annual number of uDCD donors was heterogeneous. Compared with non-effective donors, effective donors were significantly younger (48.1 {+/-} 12.4 vs 53.0 {+/-} 10.7 years, p=0.03) and had fewer comorbidities such as hypertension (13.8% vs 33.0%, p=0.018) and diabetes (4.1% vs 16.6%, p=0.027). Although effective donors had a shorter cannulation time (25.6 {+/-} 13.9 vs 29.1 {+/-} 11.9 min, p=0.09), the difference was not statistically significant; however, cardiocompressor time did show a significant difference (58.9 {+/-} 17.7 vs 65.8 {+/-} 18.2 min, p=0.03). ConclusionsuDCD was a useful source of transplantable organs, mainly kidneys (two out of every three perfused patients became donors), in the current context of scarcity of brain-dead donors. Shorter warm ischemia times (cardiocompressor and cannulation times) were significantly associated with more effective organ donation. The multidisciplinary transplant team may benefit from perfusion professionals with expertise in extracorporeal oxygenation therapy.

Abstract Background: ST-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. Objective: To 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. Methods: This 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. Results: The 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. Conclusions: CK-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.

ObjectiveCerebral Embolic Protection Devices (CEPs) have been designed to minimize the risk of periprocedural stroke. The clinical significance of these devices, however, is still under debate. AimsWe aimed to compare periprocedural neurological outcomes and mortality in patients undergoing transfemoral transcatheter aortic valve replacement (TF-TAVR) with versus without CEP. MethodsA single-center retrospective analysis of 1101 patients undergoing transfemoral TAVR from August 2017 to May 2025 was performed. CEPs were used routinely at our institution whenever feasible beginning with October 2019. The primary outcome was defined as the incidence of ischemic stroke occurring within 3 days postoperatively. Secondary endpoints included overall neurological outcomes defined as a combined endpoint of stroke, transient ischemic attack (TIA) and delirium within 3 days and short-term all-cause mortality. ResultsOverall, 809 underwent TF-TAVR with CEP, while 292 were treated without. The primary endpoint of clinical ischemic stroke occurred less frequently in the CEP group (1.4% vs. 4.1%), and the group difference revealed a significant result in a univariable Cox regression analysis (p = 0.007). No clinically relevant differences were observed in the incidence of TIA (0.5% vs. 0.7%, p = 0.71) and postprocedural delirium (1.6% vs. 2.4%, p = 0.39). Although the 30-day mortality rate in the control group was higher, the difference did not reach statistical significance (3.9% vs. 1.9%, p = 0.06). ConclusionsThe use of neuroprotection during TAVR was associated with a reduced early periprocedural ischemic stroke.

BackgroundGuideline-directed medical therapy (GDMT) has been shown to improve mortality and/or symptoms in heart failure with reduced ejection fraction (HFrEF). Medical devices also play an important role in improved quality of life and overall symptom relief for HFrEF patients. Baroreflex Activation Therapy (BAT) increases parasympathetic nervous system activity by stimulating the carotid baroreceptors, thereby reducing symptoms. Herein, we analyzed the effects of BAT on hospitalization, atrial arrhythmia (AA), and ventricular arrhythmia (VA) rates. MethodsA retrospective cohort study was conducted consisting of HFrEF patients treated with BAT at Keck Hospital of USC between 11/2014 and 11/2022. We compared median pre-BAT hospitalization, AA, and VA rates to post-BAT rates at both 6- and 12-months using Wilcoxon Signed Rank tests. ResultsAmong 31 patients on BAT, 38.7% met criteria for receiving all four GDMT classes for at least 12 months prior to BAT. Among these, 91.7% had an implantable cardioverter defibrillator (ICD) implanted for [&ge;]12 months pre- and post-BAT. Average pre- vs. post-BAT all-cause hospitalization rates were significantly different only at 12 months [1.3 {+/-} 1.4 vs 0.3 {+/-} 0.9, respectively (p=0.05)]. Borderline significant pre-post comparisons were noted including decreased VA rate at both 6 and 12 months and increased AA rate at 12-months (p=0.06 for all). ConclusionIn HFrEF patients on full GDMT, BAT was associated with a significant reduction in hospitalization rates at 12 months. There were no significant changes in AA or VA rates.

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.

BackgroundScreening for atherosclerosis focuses on identifying Standard Modifiable Risk Factors (SMuRFs), including diabetes, hypertension, hyperlipidaemia, and smoking. PurposeTo compare the extracardiac thoracoabdominal atherosclerotic plaque burden, as measured by computed tomography angiography (CTA), among heart transplant candidates with ischemic or non-ischemic cardiomyopathy (ICM, NICM), and evaluate potential associations between plaque burden and SMuRFs. MethodsThis retrospective study identified heart transplant candidates with ICM or NICM matched for age and sex, undergoing thoracoabdominal CTA. Patients were classified as with SMuRFs or SMuRF-less. Extracardiac thoracoabdominal non-calcified and calcified atherosclerotic plaque was classified as present or absent across 78 arterial segments per patient. ResultsAmong included patients (n=167, median [interquartile range] age 58 [53-63] years, 16% female, 51% NICM), 40 patients (24%) were SMuRF-less (ICM: 16/82 (20%), NICM: 24/85 (28%), age 56 [50-67] years). Overall, out of 13,026 arterial segments analysed, 1,746 (13%) were affected by atherosclerotic plaque (9 [4-15] segments per patient). ICM had a higher total plaque burden than NICM (11 [7-18] vs 6 [3-11] segments per patient, p<0.001). SMuRF-less patients showed no difference in non-calcified, calcified, or total plaque burden compared to patients with SMuRFs, among all patients (ICM+NICM, p>0.17) and within the ICM and NICM groups, respectively (p>0.30). ConclusionsThe burden of extracardiac thoracoabdominal atherosclerotic plaque is higher among heart transplant candidates with ICM. However, it does not differ between SMuRF-less or those with SMuRFs, regardless of underlying ICM or NICM. The prevalence of SMuRFs is not an effective marker to determine the need to screen for extracardiac atherosclerotic plaque among heart transplant candidates. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/26347056v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1aff6b1org.highwire.dtl.DTLVardef@16cfb07org.highwire.dtl.DTLVardef@1d4894corg.highwire.dtl.DTLVardef@81e9d3_HPS_FORMAT_FIGEXP M_FIG C_FIG

Background Disparities between sexes in mortality and morbidity after coronary artery bypass grafting remain incompletely understood. Multi-arterial grafting demonstrates superior outcome compared to single arterial grafting, although the optimal type of a second arterial graft and possible sex-dependent differences in grafting strategy have not been elucidated. We aim to determine whether the right internal thoracic artery or the radial artery is the optimal second arterial graft. Methods We analyzed data from 14,196 patients undergoing primary isolated coronary artery bypass grafting with the left internal thoracic artery and either right internal thoracic artery or radial artery between 2013 and 2022 from the Netherlands Heart Registration. Patients were stratified by sex and type of second arterial graft. Inverse probability treatment weighting was used to balance baseline characteristics. The primary outcome was long-term mortality. Secondary outcomes included short-term complications and repeat revascularization. Results In both sexes, the choice of second arterial graft did not significantly impact long-term survival. Postoperative arrhythmias were more prevalent in both sexes following right internal thoracic artery use (p<0.001). The radial artery was associated with higher rate of repeat revascularization in men (p=0.044 at 5 years follow-up) and more cerebrovascular accidents in women (0.9% vs 0.2%, p=0.028). Conclusion The choice of second arterial graft did not affect long-term survival in either sex. The radial artery was associated with an increased risk of repeat revascularization in men and more cerebrovascular accidents in women. These results underscore the need for further research in the field of sex-specific considerations in operative strategy.

Background: Coronary artery bypass grafting (CABG) to physiologically non-significant coronary artery stenosis may result in graft failure due to competitive native flow. We evaluated whether an instantaneous wave-free ratio (iFR)-guided revascularization strategy improves graft patency and clinical outcomes compared to conventional angiography-guided CABG. Methods: In this prospective, randomized, single-blinded trial, patients with multivessel disease and at least one angiographically intermediate stenosis (50%-75%) were randomized to either CABG guided by angiography alone or angiography supplemented with iFR assessment groups. The primary endpoint was graft patency (occlusion or hypoperfusion of the graft) evaluated by coronary computed tomography angiography (CCTA) at 2, 12, and 36 months. Results: At 36 months, 78% of the patients completed follow-up. Left internal mammary artery (LIMA)-to-left anterior descending (LAD) artery graft patency was significantly higher in the iFR-guided group than in the angiography-guided group (80.5% vs. 56.8%; absolute risk difference, 23.7% [95% CI, 3.7%-43.8%]; RR, 1.42 [95% CI, 1.03-1.95]; P = 0.03). Saphenous vein graft patency also improved with iFR guidance (90.2% vs. 70.3%; P = 0.046). Major adverse cardiac and cerebrovascular events (MACCE) were similar between groups (28% vs. 20%; RR, 1.40 [95% CI, 0.69-2.85]; P = 0.48). Conclusions: iFR-guided CABG advocates significantly improved mid-term graft patency compared with angiography-guided CABG by optimizing surgical target selection and reducing competitive flow.

BackgroundThere is no consensus on a risk threshold for sudden cardiac death (SCD) that could be used in practical design and evaluation of prediction models and decisions regarding implantable cardioverter-defibrillator (ICD) therapy. MethodsBaseline assumptions for a simulation framework were derived from previous randomized controlled trials (n=18) to identify minimal SCD risk threshold that would translate to mortality benefit by ICD therapy also considering the effect of competing non-sudden mortality. ICD efficacy to prevent SCDs and other data for simulations were estimated using inverse-variance weighted meta-analysis of included trials. Number needed to treat (NNT) was evaluated over a five-year horizon ([&le;]21 defined as clinically relevant). ResultsCorrelation analysis confirmed annual SCD incidence in trial populations as the key factor associating with ICD therapy effectiveness to reduce mortality (Pearsons r=0.653, p<0.01). In a simulation assuming 5% annual non-sudden mortality (pooled estimate of included RCTs) and a 56% (48-62%) efficacy for ICDs to reduce SCDs or similar events, 3% annual SCD risk ({approx}12% over five years) emerged as the lowest practical threshold even after controlling for excess (overlapping) mortality among those saved successfully from SCD by ICD therapy. The theoretical minimum threshold for annual SCD risk is 2.0%, 2.5% and 3.5% for populations with the annual incidence of non-sudden deaths 2%, 5% and 10% (assuming no overlapping mortality). ConclusionsEven under substantial competing risk, a 3% annual SCD threshold appears an optimal minimum threshold for identifying patients most likely to benefit from ICD therapy if severe mortality overlap is not observed. Key QuestionsWhat is the minimal risk threshold after which ICD therapy will likely lead to meaningful reduction in overall mortality. This information is needed in practical design of clinical trials and evaluation and development of prediction models Key FindingAnalysis of the data extracted from previous randomized controlled trials revealed that annual SCD risk should be at least 3% in most scenarios (with the annual incidence of non-sudden mortality [&le;]5%) for ICD therapy to be effective. Take-home MessagePrimary prevention SCD and risk models targeted to identify high-risk individual should aim for identifying patients with 3% or higher annual risk for SCD.

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

STRUCTERED ABSTRACTO_ST_ABSBACKGROUNDC_ST_ABSCoronary artery bypass graft (CABG) is a widely performed procedure for coronary artery disease (CAD), yet its association with Impaired Cognition (IC), i.e., mild-cognitive impairment or all-cause dementia, while accounting for APO ({varepsilon}) genotype, remains unclear. METHODSWe analyzed AllofUS participants with CAD (Age[&ge;]60 yrs) from 2017-2023. We defined CAD as a history of angina/myocardial infarction/chronic ischemic heart disease or having percutaneous coronary intervention/CABG, and IC as mild cognitive impairment or all-cause dementia using ICD/SNOMED codes. We performed logistic regression analyses to assess the association between CABG and IC, adjusting for clinical factors (age, sex, hypertension, diabetes, hyperlipidemia, depression, stroke, smoking, alcohol use, statin/antihypertensive/antidiabetic use), social determinants (self-reported race/ethnicity, income, employment), and APO ({varepsilon}) genotypes. We further performed stratified analyses across APO ({varepsilon}) genotypes ({varepsilon}2/{varepsilon}2, {varepsilon}2/{varepsilon}3 {varepsilon}3/{varepsilon}3, {varepsilon}2/{varepsilon}4, {varepsilon}3/{varepsilon}4, {varepsilon}4/{varepsilon}4). We defined significance at p [&le;] 0.05. RESULTSWe included 22,349 with CAD and identified 908 with IC after CAD till 2023. 40% were females, 70% were White, 12% were Black, and 9% were Hispanic. The proportion of IC was higher (5.1% vs 3.5%, p=1e-08) in CABG (n=8,135) vs non-CABG (n=14,214). After adjusting for clinical factors, social determinants, and APO ({varepsilon}) genotypes, CABG (1.23;1.06-1.41, p = 0.005) was associated with IC. In APO ({varepsilon}) stratified analysis, the association of CABG with IC was strongest in the APO {varepsilon}2/{varepsilon}3 group (1.91;1.21-3.02, p = 0.005). CONCLUSIONIn the AllofUS cohort, we observed an association between CABG and IC in CAD participants, with the strongest association in the APO {varepsilon}2/{varepsilon}3 group. Key MessageO_ST_ABSWhat is already known on this topicC_ST_ABSCoronary artery disease (CAD) and Impaired Cognitive (IC) disease, i.e., mild cognitive impairment and all-cause dementia, share genetic, sociodemographic, and clinical factors, including cardiovascular conditions like coronary artery bypass grafting (CABG) procedure. What this study addsWe observed an association between CABG and IC in CAD participants after adjusting for sociodemographic, clinical factors, and APO ({varepsilon}) effects. Further, when CAD participants were stratified across APO ({varepsilon}) groups, CABG was significantly associated with IC in the APO {varepsilon}2/{varepsilon}3 group. How this study might affect research, practice or policyOur observations highlight the role of APO ({varepsilon}) genotype evaluation in CAD patients for IC risk assessment.

BackgroundAlthough ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) are very similar regarding pathophysiology and clinical treatments, especially NSTEMI comprises a much more heterogenic group of patients and underlying diseases. We therefore aimed to assess the treatments and outcomes of both entities in a large contemporary cohort. MethodsPatients with STEMI and NSTEMI between 01/2010 to 12/2018 were identified from the largest German Health Insurance (AOK, {approx}26 million members). Patient demographics, their hospital course, adherence to guideline-directed drug therapy and overall survival were assessed. ResultsIn total 544,529 patients (mean age 74, IQR 62-82), one third of whom had a STEMI. Chronic kidney disease, peripheral arterial disease, and heart failure were more common in patients with NSTEMI. Patients with STEMI were more likely to get coronary angiograms and percutaneous coronary interventions. Although STEMI more frequently led to cardiogenic shock, the rate of serious cardiac events was lower. Mortality was higher for STEMI only within the first 30 days, whereas long-term survival rates were better. The combination of statins, angiotensin converting enzyme inhibitors /angiotensin receptor blockers, beta blockers, and oral anticoagulants or antiplatelet agents was associated with higher overall survival in patients with STEMI (hazard ratio [HR] 0.20; 95% confidence interval [95%CI] 0.18 - 0.24; p<0.001) or NSTEMI (HR 0.30; 95%CI 0.28 - 0.33; p<0.001). Nevertheless, the prescription rates decreased over time, particular in patients with NSTEMI. ConclusionClear differences between STEMI and NSTEMI were observed regarding short-and long-term survival. Guideline-recommended therapy improved long-term survival, but decreased during the follow-up period.

BackgroundAtrial fibrillation and flutter (AF/AFL) represent a major global public health challenge, contributing significantly to stroke, heart failure, and cardiovascular mortality. While previous studies have documented a rising AF/AFL burden, comprehensive comparisons of long-term trends and forecasts across regions--particularly benchmarking China against Southeast Asia, Europe, and global averages--remain limited. This study aims to quantify the AF/AFL burden across these regions from 1990 to 2021 and project trends to 2050. MethodsUsing data from the Global Burden of Disease Study 2021, we analysed the burden of AF/AFL from 1990 to 2021 in China, Southeast Asia, Europe, and globally. We examined incidence, prevalence, mortality, and disability-adjusted life years (DALYs). Advanced analytical methods, including Joinpoint regression, age-period-cohort modelling, decomposition analysis, Frontier analysis and Bayesian forecasting were employed to assess trends, drivers, and projections to 2050. FindingFrom 1990 to 2021, China experienced the most rapid increase in age-standardized incidence rate (ASIR) globally (AAPC +0.16%), with incident cases rising to 916,180, accounting for 20.43% of the global total. In contrast, Europe saw a slight decline in ASIR, while the global ASIR remained stable. China also recorded the largest increase in age-standardized prevalence rate (ASPR), whereas Europes ASPR declined. Despite rising incidence, China achieved the sharpest reduction in age-standardized mortality rate (ASMR; AAPC -0.45%), while Southeast Asias ASMR increased (AAPC +0.76%), and Europe maintained the highest ASMR globally. Frontier analysis highlighted Chinas rapid efficiency improvements in mortality reduction relative to its SDI, outperforming several high-income European countries. Projections to 2050 suggest Chinas ASIR and ASPR will continue to rise, whereas Europes are forecast to decline. Southeast Asia faces persistently increasing mortality, and global aggregates mask significant regional heterogeneity. ConclusionAF/AFL burdens are increasingly driven by population aging and metabolic risks, with heterogeneous mortality trends reflecting regional disparities in healthcare access and prevention. China s success in reducing mortality despite rising incidence highlights the impact of improved anticoagulation and stroke prevention, yet unchecked prevalence growth signals future complications. Southeast Asia s rising mortality underscores urgent needs for equitable resource allocation, while Europes stagnant burden reflects challenges in aging populations. Globally, prioritising primordial prevention--such as metabolic risk control--alongside targeted screening and gender-specific interventions, is critical to mitigating AF/AFL-related morbidity and mortality. Future efforts should integrate digital health technologies and address structural barriers to optimize care efficiency worldwide. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSPrior to undertaking this analysis, we systematically reviewed the existing epidemiological literature on atrial fibrillation and atrial flutter (AF/AFL), with a particular emphasis on global and regional comparative studies. Our searches covered PubMed, Embase, Web of Science, the Cochrane Library, and the Global Burden of Disease (GBD) repository from January 1990 to December 2023, without language restrictions. Key terms included "atrial fibrillation," "atrial flutter," "global burden," "epidemiology," "trend," and "GBD." We included studies providing representative estimates of AF/AFL burden and excluded small-sample or non-age-standardized reports. Previous analyses indicated a rising global AF/AFL burden, largely due to population aging and improved detection. However, comprehensive assessments capturing temporal dynamics, risk drivers, and forecasting across major world regions--especially benchmarking China, Southeast Asia, and Europe against global patterns--remained limited. Most studies focused on isolated regions or short spans, lacking integrative multidimensional approaches such as age-period-cohort modeling, decomposition, or Bayesian forecasting. Added value of this studyThis study provides a comprehensive and comparative assessment of the atrial fibrillation and atrial flutter (AF/AFL) burden across China, Southeast Asia, Europe, and globally from 1990 to 2021, utilizing the latest GBD 2021 data and advanced statistical methodologies, including Joinpoint regression, age-period-cohort modeling, Bayesian forecasting, decomposition analysis, and data envelopment frontier analysis. Our analysis reveals significant regional disparities against a backdrop of global stability: while the global age-standardized incidence rate (ASIR) remained stable (52{middle dot}51 in 1990 vs. 52{middle dot}12 in 2021), China experienced the most rapid increase worldwide (ASIR rising from 42{middle dot}63 to 44{middle dot}92), with a substantial number of new cases (916,180), accounting for 20{middle dot}43% of the global total (4,484,926 cases). In contrast, Europe recorded a slight decline in ASIR. China also demonstrated the most pronounced increase in prevalence globally, while Europes age-standardized prevalence rate (ASPR) declined and the global rate remained largely unchanged. Notably, China achieved a significant reduction in mortality (age-standardized mortality rate [ASMR] declining from 4{middle dot}93 to 4{middle dot}33) despite rising incidence, sharply contrasting with Southeast Asia, where ASMR increased from 2{middle dot}94 to 4{middle dot}06 (estimated annual percentage change +1{middle dot}07%)--trends potentially associated with structural challenges in Southeast Asia--while Europe maintained the highest ASMR globally (5{middle dot}10 in 2021) despite interventions. We further identified key drivers: population growth and aging accounted for the majority of the case increase in China, consistent with global demographic trends, while metabolic risk factors accelerated this trend. Gender and age analyses revealed a global pattern of later-life predominance in women and earlier onset in middle-aged groups, particularly pronounced in China. Our projections to 2050 indicate a continued rise in ASIR and ASPR in China, reinforcing its significant and growing contribution to the global AF/AFL burden, whereas other regions face divergent challenges--Southeast Asia is projected to experience persistently increasing mortality pressure, while Europe must address persistently high disability-adjusted life year (DALY) rates, masking mortality gains in an aging population. Implications of all the available evidenceThe collective evidence from this study and previous research underscores that AF/AFL remains a critical and growing public health challenge worldwide, characterized by heterogeneous patterns across regions when viewed against the global aggregate. Chinas success in reducing mortality within a rising incidence environment highlights the potential of enhanced clinical management and stroke prevention, yet its unchecked prevalence growth--especially among younger cohorts--signals a looming surge in complications absent strengthened primary prevention, a concern mirrored in many developing economies. Southeast Asias rising mortality underscores urgent needs for improved access to anticoagulation and rhythm control, while Europes stagnant burden reflects challenges in managing an aging population efficiently. These findings advocate for regionally tailored strategies that align with global frameworks but address local disparities--integrating primordial prevention (e.g., metabolic risk control) with early detection, gender-specific treatment, and equitable resource allocation. Future research should prioritize mechanistic studies of AF/AFL subtypes, real-world intervention assessments, and the integration of digital health technologies for scalable screening and management, thereby informing coordinated global actions to mitigate the evolving burden of AF/AFL.

The objective of this systematic review and meta-analysis was to identify the interventions used to manage intolerance in patients receiving statins for primary prevention of CVD and to determine the effectiveness of these interventions. This study was conducted according to the PRISMA checklist. The electronic databases MEDLINE (PubMed), SCOPUS, EMBASE, and CINAHL were searched for studies published until June 2025. Based on the NLA definition of statin intolerance, the outcomes were split into adverse effects caused by statins and statin discontinuation. In total, 1,238 studies were identified and screened. Nine studies were eligible for systematic review, and six studies were eligible for meta-analysis. The identified intervention strategies were adjuvant therapy, statin titration, replacing statins with other lipid-lowering agents and switching to different statin. The meta-analysis showed that the pooled risk ratio (RR) relative to control was 0.97 (95% CI, 0.86-1.08) in randomized controlled trials and 0.94 (95% CI, 0.63-1.42) in overall, with point estimates in favour of intervention arms. Moderate to substantial heterogeneity was observed, with I2 between 27% to 57%. Due to the smaller number of studies, no clear conclusions can be drawn regarding how the implemented interventions may affect statin discontinuation. This study showed no strong evidence that the implemented interventions reduced statin intolerance. PROSPERO registration numberCRD42024587573 HighlightsThis study found that the intervention strategies used to manage intolerance in patients receiving statins for the primary prevention of cardiovascular diseases were adjuvant therapy, statin titration, replacing statins with other lipid-lowering agents and switching to different statin. O_LIThis study showed no strong evidence that the implemented interventions reduced statin intolerance C_LIO_LIDue to the smaller number of studies, no clear conclusions can be drawn regarding how the implemented interventions may affect statin discontinuation C_LI

BackgroundIn patients with atrial fibrillation (AF) and stable coronary artery disease beyond 1 year after percutaneous coronary intervention (PCI), oral anticoagulant monotherapy is guideline-recommended; however, its efficacy and safety in patients with complex PCI remain uncertain. MethodsWe conducted a post-hoc analysis of the randomized ADAPT AF-DES trial comparing NOAC monotherapy versus NOAC plus clopidogrel in AF patients [&ge;]12 months after second- or third-generation drug-eluting stent implantation. Complex PCI was defined by one of the following characteristics: [&ge;]3 stents, [&ge;]3 lesions, bifurcation with 2 stents, total stent length [&ge;]60 mm, left main PCI, or chronic total occlusion PCI. Net adverse clinical events (NACE), ischemic composite outcomes, and bleeding composite outcomes were evaluated according to PCI complexity. ResultsAmong 960 patients, 247 (25.7%) underwent complex PCI and 713 (74.3%) underwent noncomplex PCI. NOAC monotherapy was associated with a lower risk of NACE compared with combination therapy in both the complex PCI group (9.5% vs 21.5%; hazard ratio 0.42, 95% confidence interval 0.21-0.83; P=0.01) and the noncomplex PCI group (9.6% vs 15.7%; hazard ratio 0.59, 95% confidence interval 0.39-0.90; P=0.02), with no significant interaction. Ischemic outcomes did not differ significantly between treatment strategies regardless of PCI complexity, whereas bleeding outcomes were consistently lower with NOAC monotherapy in both complex and noncomplex PCI groups. ConclusionsIn this post hoc analysis of the randomized ADAPT AF-DES trial, the clinical benefits of NOAC monotherapy beyond 12 months after PCI--characterized by reduced bleeding without a significant increase in ischemic events--were consistent regardless of PCI complexity. While hypothesis-generating, these findings support a long-term antithrombotic strategy prioritizing bleeding reduction in patients with AF, irrespective of prior PCI complexity. Trial registrationURL: http://www.clinicaltrials.gov; Unique identifier: NCT04250116. Clinical perspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIIn a randomized population of patients with AF and prior drug-eluting stent implantation, the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel were evaluated according to anatomic PCI complexity. C_LIO_LIAmong patients with prior complex PCI, NOAC monotherapy was not associated with an increased risk of ischemic events and was associated with a substantial reduction in bleeding. C_LI What are the clinical implications?O_LINOAC monotherapy beyond 1 year after PCI was supported in patients with AF, including those with prior complex PCI. C_LIO_LILong-term antithrombotic decisions may place greater emphasis on bleeding risk than PCI complexity. C_LIO_LIThe optimal duration of combination antithrombotic therapy after complex PCI in patients with AF remains to be determined. C_LI

BackgroundCoronary artery tortuosity (CAT) is often viewed as a benign angiographic finding; however, emerging evidence suggests its potential hemodynamic significance, particularly in non-atherosclerotic cardiomyopathies such as Takotsubo syndrome (TS). ObjectivesThis study aimed to investigate the prevalence and hemodynamic implications of CAT in patients diagnosed with Takotsubo cardiomyopathy (TCM) and to evaluate the association between the severity of tortuosity and myocardial injury markers, recovery of ventricular function, and other clinical variables. MethodsA retrospective review of 100 patients with TCM from the Baptist Memorial Hospital network (2015-2025) was conducted. Tortuosity severity was quantified using angiographic criteria per Eleid et al. (2014). Associations between CAT and biochemical or echocardiographic parameters were evaluated using multiple linear regression and non-parametric tests. ResultsCAT was highly prevalent (85.1%) in this TCM cohort, with a mean tortuosity index of 3.26--significantly higher than in general angiography populations. No significant correlations were found between tortuosity severity and peak troponin levels (p = .588) or ejection fraction (EF) at presentation (p = .820). Full EF recovery (55-65%) at [&ge;]3 months occurred in 70.7% of patients and was not significantly associated with prior cardiomyopathy, coronary artery tortuosity index or baseline troponin levels. ConclusionsCAT appears markedly more prevalent among patients with TCM, although its severity does not correlate with biomarker elevation or EF recovery. These findings suggest that coronary tortuosity may contribute to the hemodynamic environment predisposing to TS, without directly determining the extent of myocardial dysfunction or recovery.

Abstract Background: Despite widespread adoption of contemporary guideline-directed medical therapy (GDMT), patients with heart failure with reduced ejection fraction (HFrEF) continue to experience substantial residual morbidity and mortality. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated cardiometabolic benefits in diabetes and obesity, but their role in HFrEF remains uncertain. Objectives: To evaluate whether the addition of GLP-1RAs to optimized GDMT is associated with improved clinical outcomes in patients with HFrEF (NYHA class II-IV). Methods: We conducted a retrospective, multicenter cohort study using the TriNetX Research Network. Adults ([&ge;]18 years) with HFrEF (LVEF [&le;]40%) receiving GDMT between January 2020 and October 2024 were included. Patients treated with GLP-1RAs were compared with those on GDMT alone. After 1:1 propensity score matching, 1,518 patients were included in each cohort. Outcomes over 2 years included all-cause mortality, major adverse cardiovascular events (MACE), critical care utilization, and acute kidney failure. Time-to-event analyses were performed using Kaplan-Meier methods and Cox proportional hazards models. Results: In the matched cohort (mean age [~]63 years, [~]33% female), GLP-1RA use was associated with significantly lower all-cause mortality compared with GDMT alone (12.8% vs 23.8%; hazard ratio [HR] 0.48; 95% CI 0.40-0.57; p<0.001), corresponding to an absolute risk reduction of 11.0%. MACE was also reduced (35.8% vs 47.4%; HR 0.64; 95% CI 0.58-0.72; p<0.001). Additionally, GLP-1RA therapy was associated with lower critical care utilization (18.4% vs 28.9%; HR 0.55; 95% CI 0.47-0.64; p<0.001) and reduced acute kidney failure (29.2% vs 37.3%; HR 0.67; 95% CI 0.59-0.76; p<0.001). Rates of pancreatitis and substance-related disorders were low and not significantly different between groups. Conclusions: Among patients with HFrEF receiving contemporary GDMT, adjunctive GLP-1RA therapy was associated with significant reductions in mortality, cardiovascular events, and healthcare utilization. These findings support the potential role of GLP-1RAs as a novel, mechanism-complementary therapy in HFrEF. Prospective randomized trials are needed to confirm these observations and determine whether GLP-1RAs should be incorporated as a fifth pillar of GDMT.