European Heart Journal

BackgroundBoth acute myocardial infarction (AMI) and acute myocarditis are characterised by cardiac troponin release as a marker of cardiomyocyte injury. While peak troponin is widely accepted as a surrogate marker for infarct size in AMI, its relationship with myocardial injury in acute myocarditis is unclear. This study aimed to quantify and compare the association between peak high-sensitivity cardiac troponin and cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) extent in patients with AMI versus acute myocarditis. MethodsPatients undergoing CMR imaging and measurement of high-sensitivity cardiac troponin I during hospital admission were retrospectively included. LGE extent was quantified in grams using the semi-automated expectation-maximization weighted intensity algorithm (EWA). ResultsCompared to patients with acute myocarditis (n=47), patients with AMI (n=49) had higher peak troponin levels (median [interquartile range] 32,470 [3,109-104,699] vs 7,295 [1,857-22,550] ng/L, p=0.002), larger LGE extent (25 [13-56] vs 10 [6-17] g, p<0.001), and lower left ventricular ejection fraction (45 [36- 52] vs 55 [49-58] %, p<0.001). Peak troponin was moderately positively correlated with LGE extent in both AMI (rho=0.56, p<0.001) and acute myocarditis (rho=0.58, p<0.001). However, the ratio of peak troponin to LGE mass was higher in AMI compared to acute myocarditis (1,299 [419-3233] vs 909 [310-1446] ng/L/g, p=0.02). ConclusionsPeak cardiac troponin correlates positively with LGE extent in both AMI and acute myocarditis, but the magnitude of LGE and LV systolic dysfunction is greater in AMI. Also, AMI typically has an approximately 40% greater amount of troponin release per unit LGE mass compared to acute myocarditis. This suggest that troponin-based estimates of myocardial injury size estimated by LGE are not directly interchangeable between ischaemic and inflammatory myocardial diseases.

BackgroundMetabolic vulnerability index (MVX), a novel biomarker of systemic inflammation and metabolic malnutrition, is associated with mortality in patients with cardiovascular diseases. Nevertheless, little is known about its association with cardiometabolic diseases (CMDs) and multimorbidity (CMM). We aimed to examine the associations of MVX with the risk of individual CMDs, their progression to CMM, and all-cause mortality in the general population. MethodsIn a prospective cohort of 218,635 UK Biobank participants free of CMDs, MVX was calculated based on plasma metabolomics data. CMM was defined as coexistence of two or more CMDs, including coronary heart disease (CHD), stroke, and type 2 diabetes mellitus (T2DM). Cox proportional hazard and multi-state models were employed to evaluate the associations of MVX with the risks of individual CMDs, CMM, and all-cause mortality. ResultsDuring a median follow-up of 14.4 years, 27,805 (12.7%) participants developed at least one CMD, 3,006 (1.4%) progressed to CMM, and 14,211 (6.5%) died. Each standard deviation increase of MVX score was associated with 9% (95% confidence interval: 8%-10%), 11% (7%-15%), and 12% (10%-14%) higher risks of developing CMDs, CMM, and mortality, respectively. The MVX-CMM associations were more prominent in females and in the sequential onset pattern of T2DM followed by CHD or stroke. Multi-state model analysis further uncovered consistent associations between higher scores of MVX and higher risks of transitions from CMDs free to CMD, subsequently to CMM, and to death. ConclusionsHigher MVX scores were significantly associated with higher risks of incident CMDs, their progressions to CMM, and all-cause mortality. These results underscored the potential of MVX in the primary prevention and management of CMDs and CMM.

BackgroundHeart failure (HF) is an increasingly common complication among patients with type 2 diabetes (T2D), yet its early detection remains challenging, especially in those with concomitant chronic kidney disease (CKD). NT-proBNP is a key biomarker for diagnosing and prognosticating HF, but its reference thresholds are influenced by renal function, age, and ethnicity. Current guideline cutoffs, largely derived from Western populations, may not apply to Asian patients. MethodsThis retrospective cohort study included 10,587 adults with T2D who underwent NT-proBNP testing between 2006 and 2021 at the National Taiwan University Hospital. Patients with prior HF were excluded. Generalized additive models identified NT-proBNP thresholds associated with HF hospitalization, and Kaplan-Meier analysis validated outcome separation. Subgroup analyses were stratified by age, sex, body mass index (BMI), and estimated glomerular filtration rate (eGFR). ResultsDuring a mean follow-up of 3.5 years, 1,892 (17.9%) patients were hospitalized for HF. NT-proBNP levels of 179 pg/mL (outpatient) and 728 pg/mL (emergency) marked inflection points for rising event risk (log-rank p < 0.0001). Age-specific analyses showed progressive increases in optimal thresholds: from 85 (<50 years old), 150 (50-74 years old) and 290 pg/mL ([&ge;]75 years old) in outpatients, and from 310, 600 and 1,165 pg/mL, respectively, in emergency settings. In the BMI-stratified analysis, NT-proBNP thresholds demonstrated an inverse relation with BMI. Considering renal function, the optimal cutoffs were 100, 310, and 935 pg/mL for eGFR > 60, 30-60, and < 30 mL/min/1.73 m{superscript 2}, respectively; in the emergency cohort, the corresponding thresholds were 290, 835, and 3,905 pg/mL. ConclusionsThis large Asian cohort defines setting- and renal function-specific NT-proBNP thresholds for predicting HF hospitalization in patients with T2D. The lower optimal cutoffs compared with Western guidelines highlight the need for ethnicity-adjusted diagnostic criteria to improve early identification and risk stratification of HF in clinical practice. What is new?O_LIIn a large real-world Asian cohort of patients with type 2 diabetes, we identified setting-specific NT-proBNP thresholds (179 pg/mL outpatient; 728 pg/mL emergency) associated with heart failure hospitalization risk. C_LIO_LIAge-, BMI-, and kidney function-stratified cutoffs revealed substantial heterogeneity in optimal NT-proBNP thresholds. C_LIO_LICompared with guideline-recommended values, Asian-specific thresholds were consistently lower ([~]30-40%), supporting ethnic differences in natriuretic peptide biology. C_LIO_LIA generalized additive model (GAM) captured nonlinear biomarker-risk relationships, enabling data-driven and clinically interpretable cutoff identification. C_LI What are the clinical implications?O_LIUse of ethnicity- and context-specific NT-proBNP thresholds may improve early detection of heart failure in Asian patients with type 2 diabetes. C_LIO_LIIncorporating kidney function and BMI into NT-proBNP interpretation enhances risk stratification, particularly in patients with CKD. C_LIO_LIReliance on Western guideline cutoffs may underestimate heart failure risk in Asian populations. C_LIO_LIThese findings support a precision medicine approach to biomarker interpretation and highlight the need for population-specific guideline refinement. C_LI

BackgroundVitamin D supplementation has been investigated for potential associations with cardiometabolic risk factors related to cardiovascular disease (CVD); however, findings from randomized controlled trials (RCTs) remain inconsistent. This meta-analysis aimed to assess the effects of vitamin D supplementation on cardiometabolic risk factors--including lipid profile, blood pressure, and glycaemic parameters--and to explore whether age and baseline serum vitamin D concentrations modify these associations. Research Design and MethodsWe conducted a systematic review and meta-analysis of RCTs comparing oral vitamin D supplementation with placebo in adults. PubMed, the Cochrane Library, and ClinicalTrials.gov. Risk of bias was evaluated using the Cochrane tool, and pooled effect sizes with 95% confidence intervals (CIs) were calculated using random-effects models. Results14,051 abstracts were retrieved, of which 45 were used for data analysis. Vitamin D supplementation reduced low-density lipoprotein cholesterol (LDL-C) by 0.136 mmol/L (95%CI: -0.215, -0.56), systolic blood pressure by 2.79 mm Hg (95% CI: -4.648, -0.938), fasting blood glucose by -0.11 (95%CI:-0.185, -0.036), and hemoglobin A1c by 0.164% (95%CI: -0.322, -0.006) compared with placebo. Subgroup analyses revealed reductions in SBP and LDL cholesterol among participants aged [&ge;]55 years and reductions in fasting blood glucose in participants with age < 55 years. While favourable effects on fasting blood glucose and hemoglobin A1c were observed with a baseline blood level of vitamin D of concentrations (<50 nmol/L). ConclusionsVitamin D supplementation may be associated with modest modifications in selected cardiometabolic risk factors; including systolic blood pressure, LDL-cholesterol, fasting blood glucose, and hemoglobin A1c. Age and baseline vitamin D status appear to modulate these effects. The clinical relevance of these modest effects remains uncertain. Well-designed RCTs with standardized protocols are required to clarify potential effect modification by age and baseline vitamin D status. Trial RegistrationPROSPERO (CRD42020165293) FundingThis research received funding from the Hashemite University, P.O. Box 330127, Zarqa 13133, Jordan

BackgroundElevated resting heart rate (HR) and atrial cardiopathy are each linked to higher mortality risk, yet their interrelationship and joint prognostic value remain unclear. MethodsWe analyzed 7,326 adults (mean age 59 {+/-} 13 years) without cardiovascular disease from the Third National Health and Nutrition Examination Survey with available electrocardiograms. Atrial cardiopathy was defined by electrocardiogram as abnormal P-wave axis or deep terminal P-wave negativity in V1. Multivariable logistic regression assessed cross-sectional associations between HR categories and atrial cardiopathy. Cox proportional hazards models evaluated independent and joint associations of HR categories and atrial cardiopathy with all-cause mortality. ResultsAtrial cardiopathy was present in 1,833 participants (13.5%). After adjustment, sinus tachycardia ([&ge;]100 bpm) was associated with higher odds of atrial cardiopathy (OR 1.76, 95% CI 1.06-2.92), whereas sinus bradycardia ([&le;]50 bpm) was associated with lower odds (OR 0.61, 95% CI 0.43-0.84). Each 10-bpm HR increase corresponded to 25% higher odds of atrial cardiopathy. Over a median 13.8-year follow-up, 2,415 deaths (33.0%) occurred. Sinus tachycardia (HR 3.58, 95% CI 2.61-4.91) and atrial cardiopathy (HR 1.27, 95% CI 1.16-1.39) were independently associated with mortality. Individuals with both conditions had the highest risk (HR 4.11, 95% CI 2.63-6.41). Associations varied by age and race. ConclusionsElevated resting HR is associated with higher odds of atrial cardiopathy, and their coexistence confers markedly increased mortality risk. Integrating resting HR into atrial cardiopathy metrics may enable granular population-level risk profiling.

Background and AimSedentary lifestyle and obesity are considered to be significant risk factors that create a pathway for the appearance of the sedentary cardiac phenotype consisting of cardiac atrophy, myocardial stiffening, and altered haemodynamics. Although exercise training has the potential to reverse this detrimental process, the literature data on the magnitude of improvements and the certainty of evidence are inconsistent. This systematic review and meta-analysis aimed to evaluate the effects of exercise interventions on cardiac morphology, systolic/diastolic function, and haemodynamics in sedentary and obesity-prone individuals. MethodIn accordance with the PRISMA guidelines, the study was conducted by searching the PubMed, Web of Science, and Scopus databases from 1990 to 2025 without applying any filters, using Covidence software. As a result of this comprehensive search, 15 randomised controlled trials (RCTs; N=559) comparing exercise training with a control group in sedentary individuals were included in the analysis. Data were pooled using the Standardised Mean Difference (SMD) and a random-effects model. Publication bias and methodological robustness of the results were tested using the Egger regression test, the Trim-and-Fill method, and Leave-One-Out sensitivity analysis. The certainty of the evidence was graded using the GRADE system. ResultsExercise training was associated with a significant reduction in resting HRs and SBPs, which was a strong improvement in the haemodynamic profile. The improvements in SV and LVEF, although on the statistical threshold in the primary analysis, were statistically significant and methodologically stable in the Leave-One-Out sensitivity analysis, which excluded confounding studies. The exercise training was associated with a marked improvement in the E/A ratio and S wave, and the triggering of a physiological athletes heart-like eccentric hypertrophy, defined by improvements in LVMass and LVEDV. The exercise training was associated with diastolic adaptation and mass increase, with HIIT being the most superior method for diastolic adaptation and mass increase, and aerobic exercise being the most effective method for blood pressure reduction. Importantly, the meta-regression analyses revealed two important findings: first, the improvement in blood pressure and diastolic function was independent of weight loss; second, the improvement in structure and function was linearly related to improvements in body composition. ConclusionExercise acts as a cardiac polypill reversing the sedentary phenotype by improving hemodynamics and diastolic function independently of weight loss, while linking structural remodeling to BMI optimization; our data prioritize HIIT for structural/diastolic gains and Aerobic training for blood pressure control.

BackgroundElevated resting heart rate is associated with increased mortality, but the underlying mechanisms remain incompletely understood. Subclinical myocardial injury (SCMI), defined by a Cardiac Infarction/Injury Score (CIIS) [&ge;]10, represents silent cardiac damage that predicts poor cardiovascular (CV) outcomes and may partially explain this association. MethodsWe analyzed 7,152 participants from NHANES III who underwent ECG recording and were free of cardiovascular disease. Heart rate was categorized as bradycardia ([&le;]50 bpm), normal (>50-<100 bpm), or tachycardia ([&ge;]100 bpm). Mortality was assessed through National Death Index linkage. Logistic and Cox regression models evaluated associations with SCMI and mortality, respectively, and attenuation was assessed by change in hazard ratios after adjusting for SCMI. ResultsSCMI was present in 1,744 (24.3%) participants. Tachycardia was associated with increased odds of SCMI (adjusted OR 2.34, 95% CI 1.42-3.88). Over 13.9 years median follow-up, 2,311 (32.3%) died from all causes and 933 (13.1%) from CV causes. Tachycardia was associated with increased all-cause mortality (HR 3.58, 95% CI 2.63-4.88) and CV mortality (HR 2.05, 95% CI 1.06-3.79). Adjustment for SCMI attenuated the tachycardia-CV mortality association by 8.6% and all-cause mortality by 5%. Bradycardia was not associated with SCMI or mortality. ConclusionThese findings suggest that SCMI partially mediates the heart rate-mortality relationship and that ECG-based assessment of SCMI may enhance risk stratification in individuals with elevated resting heart rate.

Subclinical rheumatic valvular disease is a significant yet underdiagnosed contributor to the global rheumatic heart disease (RHD) burden. Early detection through population screening is essential to prevent its progression to severe RHD. Rhythm changes and prolongations of PR and QTc intervals in the ECG are described in the advanced RHD cases. However, these parameters were not yet studied in asymptomatic RHD. We aimed to investigate the potential of ECG biomarkers for screening RHD in asymptomatic schoolchildren. ECG tracings from 611 schoolchildren aged 10 to 20 years were selected from a cohort screened for RHD in four schools in an RHD-endemic region. Confirmatory diagnoses were based on echocardiographic findings, where 564 (F=326, M=238) were healthy, and 47 (F=28, M=19) were positive for RHD (24 borderline RHD and 23 definite RHD). Independent, blinded reviewers manually annotated the ECGs and PR interval (PR), P-wave dispersion (PWd), and the ratio between the P-wave duration and PR interval (Pw/PR) were analyzed. The mean age of the study cohort at diagnosis was 16.1 {+/-} 2.5 years, and 58% of the participants were females. Atrial fibrillation was seen in 8% (n=4), and prolonged PR in 2% (n=1) of RHD-positive cases. The mean {+/-} std for normals vs RHD is (PR, 138{+/-}19 vs 150{+/-}19), (Pw/PR, 0.75{+/-}0.06 vs 0.71{+/-}0.07), and (PWd, 49{+/-}14 vs 56{+/-}17). The PR (p<0.001), Pw/PR (p<0.001), and PWd (p=0.008) showed a significant difference between healthy and RHD-positive subjects. The PR was increased consistently with severity across age groups above and below 16 years. The PR, PWd, and Pw/PR can serve as non-invasive biomarkers for the screening of RHD in at-risk schoolchildren. Monitoring alterations in these markers at an early stage of RHD is crucial for enabling prompt management and follow-up. It is thus evident that ECG can support an intermittent ambulatory RHD screening in resource-limited settings.

Abstract Introduction Cardiovascular disease (CVD) is an important complication of type 2 diabetes (T2D). Current incident CVD-prediction models use single baseline measurements and achieve moderate performance in people with T2D, with C-indices around 0.7. Modern healthcare registries contain repeated measurements of HbA1c, LDL-cholesterol and eGFR, which could carry incremental predictive value. However, the added value of trajectory measures for CVD-risk prediction remains unclear. We aimed to investigate the utility of HbA1c, LDL-cholesterol and eGFR trajectory measures for incident CVD-risk prediction in people with T2D. Methods We studied 83,326 people with T2D from Danish nation-wide registers, who were without a CVD-history at baseline (January 1st 2015), and had [&ge;]2 recorded HbA1c, LDL-cholesterol and eGFR measurements between 2012-2014. Their last measurement was considered as baseline. Across 2012-2014, three types of paired trajectory measures were calculated for each participant (mean & standard deviation (SD), median & interquartile range (IQR), and intercept & slope from a fitted growth model), for HbA1c, LDL-cholesterol, and eGFR, respectively. Reference Cox-regression models for CVD-events (ICD-10 codes assessed prospectively from 2015- 2020) included only baseline measurements (age, sex , age at T2D onset, HbA1c, LDL-cholesterol, HDL-cholesterol, eGFR, and medication use). Next, the paired trajectory measures were sequentially added to the reference model, computing Hazard Ratios, C-indices and Net reclassification index (NRI) with 95% confidence intervals. Lastly, a combined model was fitted. Results At baseline, mean age was 65 (SD{+/-}12), median HbA1c was 48 (mmol/mol, IQR43-56), and 48% were female. During a median 6 years of follow-up 11,280 (14%) people had a CVD-event (ischemic heart disease: 40%; stroke: 32%; heart failure: 24%; CVD-mortality: 5%). Accounting for the reference model, trajectory measures of dispersion and change were associated with CVD-events, with hazard ratios {approx} 1.1 for HbA1c and eGFR, and >1.4 for LDL-cholesterol. Measures centrality did not show an association with CVD events. Addition of trajectory measures produced minimal gains in discrimination (C index {Delta} +0.001-+0.003) but modest improvements in net reclassification (continuous NRI {approx} +3-+9%). Conclusions Trajectory dispersion or change measures for HbA1c, eGFR and especially LDL-cholesterol, easily obtained from routine data, might moderately enhance incident CVD-risk prediction in people with T2D.

Background and AimsDespite advances in reperfusion and medical therapy, survivors of acute myocardial infarction (AMI) remain at risk for adverse left ventricular remodeling (LVR), a precursor to heart failure. Building on prior work outlining 12-month biomarker trajectories linked to early ventricular dysfunction, we aimed to assess whether these circulating biomarkers predict long-term adverse LVR. MethodsWe prospectively enrolled 155 patients experiencing their first AMI. Clinical, biochemical, and echocardiographic data were obtained at pre-percutaneous coronary intervention (pre-PCI), 24 h post-PCI, discharge (day 3), 6 months, and 12 months. Adverse LVR was defined as an increase of [&ge;]15 % in left ventricular end-systolic volume at 12 months. ResultsAdverse LVR occurred in 34 % of patients and was associated with cardiometabolic dysregulation (higher glucose, triglycerides, BMI, HOMA-IR; lower HDL-C). Among the six baseline biomarkers, only insulin-like growth factor-binding protein 2 (IGFBP-2) differed significantly between groups (p = 0.021) and remained independently associated in multivariable analysis (p = 0.036). Inclusion of IGFBP-2 increased the predictive models area under the receiver-operating characteristic curve from 0.735 to 0.801. ConclusionsIGFBP-2 is an independent predictor of adverse LVR following AMI, highlighting the interplay between metabolic dysfunction and maladaptive remodeling. Incorporating IGFBP-2 into clinical risk models could improve stratification and guide precision therapies for high-risk patients.

We performed a systematic review and meta-analysis of randomized controlled trials evaluating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus placebo in adults with heart failure (HF), searching PubMed, Cochrane CENTRAL, and ClinicalTrials.gov through February 2026. The primary outcome was the composite of cardiovascular death and first HF hospitalization. Random-effects meta-analysis used restricted maximum likelihood estimation with Hartung-Knapp-Sidik-Jonkman adjustment. We included 14 studies (6 dedicated HF trials and 8 cardiovascular outcomes trial HF subgroup analyses) encompassing 18,558 patients, of whom 2,499 were randomized in dedicated HF trials. The primary composite did not reach statistical significance (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.73-1.01; P=0.067; I2=47%). GLP-1 RAs significantly reduced all-cause mortality (HR 0.87, 95% CI 0.81-0.93; P<0.001; I2=0%), major adverse cardiovascular events (HR 0.83, 95% CI 0.73-0.95; P=0.019), and improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (+7.4 points, 95% CI 6.3-8.5) and 6-minute walk distance (+17.6 m, 95% CI 13.4-21.7). Excluding the FIGHT trial (acute HFrEF) yielded a significant primary composite (HR 0.83, P=0.011). The mortality signal was driven primarily by CVOT subgroups; the largest dedicated HFpEF trial (SUMMIT) showed numerically higher mortality (HR 1.25). The strongest evidence supports GLP-1 RAs in HFpEF with obesity. HighlightsO_LIPrimary composite of CV death + HHF was not significant (HR 0.86, P=0.067) C_LIO_LIGLP-1 RAs reduced all-cause mortality (HR 0.87) with no heterogeneity C_LIO_LIKCCQ-CSS improved by 7.4 points and 6MWD by 17.6 m in HFpEF trials C_LIO_LIMortality benefit driven by CVOT subgroups, not dedicated HF trials C_LIO_LIStrongest evidence supports GLP-1 RAs in HFpEF with obesity C_LI

AimsThis study aimed to examine the prevalence of malnutrition and its associations with functional capacity and quality of life (QoL) in AL and ATTR cardiac amyloidosis patients. Methods and ResultsThis cross-sectional pilot study included 29 patients with confirmed CA (14 AL, 15 ATTR). Data were collected between January 2020 and September 2021. Nutritional status was assessed using body mass index (BMI), anthropometric measures, and the Subjective Global Assessment (SGA). Functional capacity was evaluated via handgrip strength and the 6-minute walk test, while QoL was assessed using the SF-36 and Kansas City Cardiomyopathy Questionnaire. Malnutrition, as determined by SGA, was present in 62% of patients, with no significant difference between AL and ATTR subtypes. In contrast, BMI according to WHO criteria failed to identify any cases of malnutrition, highlighting its limited utility in this population. These results suggest that conventional indicators may underestimate nutritional impairment in CA. Although overall QoL and functional capacity did not differ significantly between nutritional groups, malnourished AL patients showed notably lower QoL scores compared with well-nourished peers. ConclusionMalnutrition is highly prevalent in cardiac amyloidosis and seems to particularly affect the AL subtype. These findings underscore the importance of routine nutritional screening and targeted interventions, as early identification and management of malnutrition may improve patients quality of life and long-term outcomes.

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

BackgroundInflammation plays a key role in atrial fibrillation (AF) pathogenesis. The empirical dietary inflammatory potential (EDIP) score predicts circulating inflammatory biomarkers and adverse cardiac outcomes, but its association with incident AF is unclear. This study aimed to examine the relationship between EDIP score and AF risk. MethodsParticipants from the Atherosclerosis Risk in Communities (ARIC) free of baseline AF who completed a validated food frequency questionnaire were included. Correlation of EDIP with inflammatory biomarkers (factor VIII, fibrinogen, von Willebrand factor, and C-reactive protein) was examined at baseline. Incident AF was ascertained using electrocardiograms, hospital records, and death certificates. Cox proportional hazards models estimated hazard ratios of AF across EDIP quantiles and per SD increase, adjusting for sociodemographic and cardiovascular risk factors. ResultsAmong 8,277 participants (54.1 years old, 51.3% women, 80% white), higher EDIP score correlated with circulating inflammatory biomarkers at baseline. Over a median 24.2 years of follow-up, 1,453 had incident AF (incident rate 8.6 per 1,000 person-years). Compared with the most anti-inflammatory diet (EDIP Q1), the most pro-inflammatory diet (EDIP Q5) was associated with increased AF risk (HR 1.21; 95% CI 1.03-1.43). Sex-stratified analyses showed a stronger association in men (HR 1.43; 95% CI 1.14-1.79), while no significant association was observed in women. ConclusionsPro-inflammatory dietary patterns are independently associated with higher AF risk in a middle-aged cohort. These findings would support incorporating dietary inflammatory load into AF risk stratification. Clinical Perspective What Is New?O_LIHigher Empirical Dietary Inflammatory Potential (EDIP) scores, indicating a more pro inflammatory diet, were associated with an increased long-term risk of atrial fibrillation (AF) in a large, biracial, community-based cohort followed for over two decades. C_LIO_LISex stratified analyses revealed a significant sex difference: higher EDIP scores were consistently associated with increased AF risk in men, whereas no significant association was observed in women, suggesting sex-specific susceptibility to EDIP. C_LIO_LIObesity modified the association between EDIP and AF, with the strongest risk observed among individuals with BMI [&ge;]30, while an inverse or attenuated association was seen among normal weight participants. C_LI What Are the Clinical Implications?O_LIDietary inflammatory load may serve as a meaningful and modifiable upstream AF risk factor, complementing conventional cardiovascular risk assessment, particularly in men and individuals with obesity. C_LIO_LIIncorporating dietary pattern assessment into routine AF risk stratification may help identify individuals who could benefit most from targeted lifestyle interventions. C_LIO_LIPublic health and clinical prevention strategies promoting anti-inflammatory dietary patterns (e.g., increased intake of fruits, vegetables, and whole grains; reduced intake of processed meats and refined carbohydrates) could meaningfully reduce AF incidence. C_LIO_LIRecognition of sex specific differences in AF pathways reinforces the need for personalized preventive strategies, as diet inflammation mechanisms appear to influence AF development more prominently in men. C_LI

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

BackgroundCirculating lipoprotein(a) [Lp(a)] levels are highly heritable and linked to atherosclerotic cardiovascular disease, yet clinical measurement rates remain low (<1%) in the United States. The high heritability of Lp(a) across populations makes genetic prediction an attractive approach for closing this testing gap, but existing polygenic scores transfer poorly across populations. Haplotype-based prediction models, which use standard genome-wide genotype data to capture common-, rare-, and structural-variation at the LPA locus, could bridge this gap, enabling opportunistic identification of individuals with elevated Lp(a) levels across diverse populations within existing large, genotyped cohorts. ObjectivesThis study sought to develop and validate a haplotype-based prediction model using genome-wide genotype data to identify individuals with elevated Lp(a) levels across diverse populations. MethodsWe developed an LPA-haplotype model using data from the All of Us Research Program and validated it in the Penn Medicine BioBank (PMBB), Mass General Brigham Biobank (MGBB), and Mount Sinai BioMe cohorts. Primary outcomes included model performance for predicting continuous Lp(a) concentrations (r{superscript 2}) and identifying elevated Lp(a) levels (>125 nmol/L) through positive predictive value (PPV) and number needed to test (NNT). ResultsAmong PMBB (n = 1856), MGBB (n = 1401), and BioMe (n = 1686) participants with available genotype and Lp(a) measurements, average age was 60 years, and 51% were female. Overall r{superscript 2} of the haplotype model was 0.46 (95% Credible Interval [CrI] 0.32 to 0.6), with similar performance across genetically inferred ancestries and cohorts. For identifying elevated Lp(a) levels >125 nmol/L the overall PPV was 0.81 (95% CrI 0.6 to 0.89), corresponding to a NNT of 1.2 (95% CrI 1.1 to 1.7) individuals predicted to have elevated levels needing to undergo clinical testing to identify one true elevation. In the full PMBB cohort (n = 49310), the haplotype model identified elevated Lp(a) at a rate of 128 per 1000 (95% CrI 125 to 130), corresponding to an estimated 14.4-fold improvement (95% CrI 13.1 to 15.9; P(improvement) = 1) in identification rate compared with the existing rate of clinical assessment. ConclusionsA haplotype-based genetic model effectively identified individuals with elevated Lp(a) levels across diverse populations, with potential utility for opportunistic screening among cohorts where genotype data is available, but Lp(a) testing rates are low.

BackgroundAdvances in wearable devices and machine-learning-based ECG analysis enable highly accurate detection of atrial fibrillation (AF) outside traditional clinical settings, leading to increasing identification of asymptomatic AF. However, the prognostic significance of AI-detected asymptomatic AF and its implications for downstream cardiovascular risk remain unclear. In contrast to clinically diagnosed AF, evidence guiding risk stratification and further evaluation in this population is limited. We therefore investigated the association between AI-detected asymptomatic AF and incident cardiovascular outcomes in a large population-based cohort. MethodsWe applied a validated open-source ECG-based deep learning model for atrial fibrillation detection (AI-AF) to 12-lead ECG recordings from participants in the UK Biobank. Participants with AI-detected AF on ECG and no prior clinical AF diagnosis were classified as asymptomatic AF (c). Kaplan-Meier curves and log-rank tests were used to compare the incidence of ischemic stroke and major adverse cardiovascular events (MACE: myocardial infarction, ischemic stroke, or cardiovascular death) across AF subgroups. Cox proportional hazards models were used to evaluate the association between AI-AF risk and incident MACE, adjusting for age, sex, current smoking, systolic blood pressure, total and HDL cholesterol, and prevalent type 2 diabetes. Follow-up was administratively censored at 6 years. ResultsThe study included 96,531 participants with mean [SD] age of 65 [8] years; 52% female; median follow-up [IQR] of 4.7 [1.6-7.2] years. ECG data were available for 64,029 participants and an additional 32,502 participants with clinically diagnosed atrial fibrillation (AF) without ECG recordings were included. Among participants without prior clinical AF and with available ECGs, 2,399 were classified as asympAF based on AI detection, while 58,879 were AF-free. Over 6 years of follow-up, the incidence of ischemic stroke was significantly higher in participants with asympAF compared with AF-free individuals (1.5% vs 0.52%, p = 7x10-7) and significantly lower than in participants with clinically diagnosed AF (1.5% vs 3.4%, p = 2x10-5). Similar patterns were observed for myocardial infarction and cardiovascular death. Using a more liberal AI-AF threshold corresponding to a 15% false-positive rate (asympAF15) yielded consistent findings: participants classified as asympAF15 had a 62% higher risk of incident MACE in adjusted Cox PH models (hazard ratio 1.6, 95% CI 1.2-2.2) over six years. ConclusionAI-detected asymptomatic AF identified individuals at elevated risk of ischemic stroke and major adverse cardiovascular events. As ischemic stroke is a hallmark complication of atrial fibrillation, these findings support the hypothesis that AI-ECG models may capture subclinical AF-related risk not detected by conventional clinical assessment. This approach may help extend the window for preventive interventions in populations without clinically diagnosed AF.

BackgroundKetone bodies have shown potential to improve cardiac metabolism and function in patients with heart failure (HF). ObjectiveTo evaluate the effects of exogenous ketone-based interventions on cardiac function in patients with HF or related cardiometabolic risk factors. MethodsWe conducted a systematic review based on a search of MEDLINE, EMBASE, CINAHL, Cochrane Library, and Scopus from inception to January 2025. Eligible studies included randomized controlled trials evaluating exogenous ketones (oral ketones or ketone infusions) compared to placebo in adults with HF or patients with risk factors for HF including type 2 diabetes mellitus, hypertension, or coronary artery disease. Paired reviewers independently screened and identified hits at title-and-abstract and full-text levels to determine eligibility and extracted data from eligible studies. Random-effects meta-analysis was performed. Effects of interventions were summarized as mean differences (MD). Risk of bias was assessed using Cochrane RoB 2.0 tool. Certainty of evidence was evaluated using the GRADE (grading of recommendations assessment, development and evaluation) approach. ResultsOut of 565 unique records, 22 full-text articles were reviewed, and 8 studies met inclusion criteria. Exogenous ketone administration increased left ventricular ejection fraction (LVEF) (MD = 3.94, 95% CI 2.18-5.70, p = 0.001), cardiac output (CO) (MD = 1.11 L/min, 95% CI 0.55-1.67, p = 0.002), heart rate (4.85 bpm, 95% CI 2.24-7.46, p = 0.003), and stroke volume (SV) (MD = 10.21 mL, 95% CI 4.06-16.35, p = 0.005). Pulmonary capillary wedge pressure (PCWP) decreased (MD = -0.93 mmHg, 95% CI -1.44 to -0.43, p = 0.003), while mean arterial pressure showed no change (MD = -1.37 mmHg, 95% CI -3.53 to 0.79, p = 0.18). ConclusionsExogenous ketone-based therapies are associated with improvements in hemodynamic markers of cardiac function, including increases in LVEF, CO, and SV, along with a reduction in PCWP. These findings suggest that ketone supplementation may offer clinical benefits for patients with HF or vascular disease.

BackgroundEvolocumab promotes coronary plaque regression in patients with coronary artery disease, but little is known regarding carotid plaques (CP). This study aimed to evaluate the impact of evolocumab on top of lipid-lowering therapy (ELLT) on carotid morphological stabilization (MS) and plaque regression (PR) compared to lipid-lowering therapy (LLT) alone. MethodsAsymptomatic patients with internal carotid stenosis[&ge;]50% and LDL-C[&ge;]100 mg/dL were randomized to ELLT or LLT and monitored by serial duplex ultrasound. The primary endpoint was a composite of 6-month-MS (i.e., switch from morphologic types I-II to III-IV) and/or 12-month-PR (i.e., reduction of carotid stenosis by at least 5% compared to baseline). The secondary endpoint was LDL-C change at 12 months. Major adverse vascular events (MAVE, i.e., cardiac death, stroke, myocardial infarction, carotid or coronary or peripheral revascularization) were recorded. ResultsA total of 170 patients were randomized. Mean carotid stenosis was 57%. At 6 months, MS occurred in the ELLT group (10.3%) only (p=0.29). At 12 months, PR was numerically more frequent in the ELLT group, without reaching statistical significance (43% versus 35.1%, p=0.42). The primary endpoint was met in 44.3% versus 35.1% (p=0.26). As compared to baseline, 6 and 12-month shifts from low to high-risk types were significantly higher in the LLT group (p=0.03). The 12-month LDL-C percentage reduction was -73.5% with ELLT, and -48.3% with LLT (p=0.0001). At 1 year, MAVE were significantly more frequent with LLT (14.6% versus 2.4%, p=0.005), and the absence of evolocumab was the only predictor (OR 7, p=0.014). ConclusionsIn patients with CP[&ge;]50% and LDL-C[&ge;]100 mg/dL, ELLT compared to LLT was associated with numerically but not statistically higher 6-month MS and/or 12-month PR. In the LLT group, 6- and 12-month changes from low to high-risk types, LDL-C, and MAVE were significantly higher. According to these results, evolocumab should be considered standard treatment for patients with CP[&ge;]50%. The study was registered at www.clinicaltrials.gov (NCT04730973) and Eudract (2020-005663-31). SHORT ABSTRACTPatients with carotid stenosis[&ge;]50% and LDL-C[&ge;]100 mg/dL were randomized to evolocumab on top of optimal lipid-lowering therapy (ELLT) or optimal lipid-lowering therapy (LLT) alone to assess the impact of ELLT on carotid plaque morphological stabilization (MS) and plaque regression (PR). At 6 and 12 months, MS and PR occurred in both groups, but were numerically higher in the ELLT group, without reaching statistical significance. In the LLT group, 6- and 12-month changes from low to high-risk types were significantly higher, and the rate of adverse vascular events was sevenfold higher. Evolocumab might become the standard treatment for patients with carotid artery stenosis [&ge;]50%. CLINICAL PERSPECTIVEO_ST_ABSWhat is new?C_ST_ABSO_LIThe CARUSO is the largest randomized trial evaluating the impact of evolocumab on top of lipid-lowering therapy (ELLT) on carotid morphological stabilization (MS) and plaque regression (PR) monitored by serial duplex ultrasound. C_LIO_LIThe primary endpoint was a composite of 6-month-MS (i.e., switch from morphologic types I-II to III-IV) and/or 12-month-PR (i.e., reduction of carotid stenosis by at least 5% compared to baseline) and was numerically higher in the ELLT group compared to lipid-lowering therapy (LLT) alone, without reaching statistical significance. C_LIO_LIThe 1-year rate of major adverse vascular events (MAVE) was sevenfold higher in the LLT group. C_LI What are the clinical implications?O_LICarotid plaque morphology is a dynamic event, and 6 and 12-month shifts from low to high-risk morphological types were significantly higher in the LLT group, thus suggesting that evolocumab added to LLT may prevent morphological deterioration. C_LIO_LIThe absence of evolocumab was the only independent predictor of MAVE; according to our results, ELLT might become the standard treatment for patients with carotid plaques [&ge;]50% and LDL-C not at target. C_LIO_LIFuture larger studies are warranted to validate our findings, assess long-term adherence to therapy, and identify subgroups with higher probability of achieving MS and PR. C_LI

BACKGROUNDDilated cardiomyopathy (DCM) presents a highly heterogeneous spectrum, including a familial subset with elevated arrhythmic risk. Traditional demographic and imaging markers, such as late gadolinium enhancement, have been inadequate for identifying high-risk patients before arrhythmic events. Remodelling of the interventricular septum--central to ventricular mechanics and conduction--may offer improved risk stratification. OBJECTIVESTo identify differences in left ventricular (LV) morphology between arrhythmic and idiopathic dilated cardiomyopathy (aDCM vs iDCM), and to identify LV remodeling patterns that link to adverse outcomes. METHODSThree-dimensional LV shape models were constructed from end diastolic cardiovascular magnetic resonance images of 102 individuals subdivided by their idiopathic or arrhythmic subgroup allocation. A statistical shape model was built using principal component analysis. A linear discriminant analysis determined shape features of the arrhythmic subgroup and increased composite arrhythmic outcome of sudden cardiac death, aborted sudden cardiac death, and sustained ventricular tachycardia. RESULTSThe idiopathic DCM group displayed larger mass, length, diameter, mass to volume ratio, and a mild spiral pattern of thicker septal walls (p=0.004). The arrhythmic DCM group displayed a more conical (wider basal and mid wall to apical diameter) LV, and the lack of the spiral septal morphology was the most significant feature (p=0.006) to identify subjects that had the composite arrhythmic outcome. CONCLUSIONThe LV morphology derived suggests a differentiation of arrhythmic DCM patients beyond size, function and LGE presence. This was distinctive and captured shape features that suggest alternate mechanisms for arrhythmic risk linked to a pattern of remodeling. Graphical AbstractAssessing LV morphology signature of arrhythmic DCM phenotype O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=114 SRC="FIGDIR/small/26346514v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1f47f7aorg.highwire.dtl.DTLVardef@dd5d08org.highwire.dtl.DTLVardef@106ef07org.highwire.dtl.DTLVardef@36eb76_HPS_FORMAT_FIGEXP M_FIG C_FIG