<div><h4>Oral Anticoagulation Use and Left Atrial Appendage Occlusion in LAAOS III.</h4><i>Connolly SJ, Healey JS, Belley-Cote EP, Balasubramanian K, ... Yusuf S, Whitlock RP</i><br /><b>Background</b><br />LAAOS III (Left Atrial Appendage Occlusion Study III) showed that left atrial appendage (LAA) occlusion reduces the risk of ischemic stroke or systemic embolism in patients with atrial fibrillation undergoing cardiac surgery. This article examines the effect of LAA occlusion on stroke reduction according to variation in the use of oral anticoagulants (OACs).<br /><b>Methods</b><br />Information regarding OAC use was collected at every follow-up visit. Adjusted proportional hazards modeling, including using landmarks of hospital discharge, 1 and 2 years after randomization, evaluated the effect of LAA occlusion on the risk of ischemic stroke or systemic embolism, according to OAC use. Adjusted proportional hazard modeling, with OAC use as a time-dependent covariate, was also performed to assess the effect of LAA occlusion, according to OAC use throughout the study.<br /><b>Results</b><br />At hospital discharge, 3027 patients (63.5%) were receiving a vitamin K antagonist, and 879 (18.5%) were receiving a non-vitamin K antagonist oral anticoagulant (direct OAC), with no difference in OAC use between treatment arms. There were 2887 (60.5%) patients who received OACs at all follow-up visits, 1401 (29.4%) who received OAC at some visits, and 472 (9.9%) who never received OACs. The effect of LAA occlusion on the risk of ischemic stroke or systemic embolism was consistent after discharge across all 3 groups: hazard ratios of 0.70 (95% CI, 0.51-0.96), 0.63 (95% CI, 0.43-0.94), and 0.76 (95% CI, 0.32-1.79), respectively. An adjusted proportional hazards model with OAC use as a time-dependent covariate showed that the reduction in stroke or systemic embolism with LAA occlusion was similar whether patients were receiving OACs or not.<br /><b>Conclusions</b><br />The benefit of LAA occlusion was consistent whether patients were receiving OACs or not. LAA occlusion provides thromboembolism reduction in patients independent of OAC use.<br /><br /><br /><br /><small>Circulation: 21 Sep 2023; epub ahead of print</small></div>

<div><h4>Mental Health Conditions Among Children and Adolescents With Congenital Heart Disease: A Danish Population-Based Cohort Study.</h4><i>Miles KG, Farkas DK, Laugesen K, Sørensen HT, Kasparian NA, Madsen N</i><br /><b>Background</b><br />Despite the known mental health burden among children with congenital heart disease (CHD), the literature is constrained by a lack of comparison cohorts and population-based follow-up data. We examined the incidence of mental health conditions among children with CHD, relative to 3 comparison cohorts.<br /><b>Methods</b><br />This population-based cohort study identified all children with CHD (<18 years of age; n=16 473) in Denmark from 1996 to 2017, through linkage of individual-level data across national registries. This allowed for complete follow-up of the population. Comparison cohorts included children from the general population (n=162 204), siblings of children with CHD (n=20 079), and children with non-CHD major congenital anomalies (n=47 799). Mental health conditions were identified using inpatient and outpatient hospital discharge codes, prescription data, and data on use of community-based psychology, psychiatry, and psychotherapy services. We computed cumulative incidence by 18 years of age, incidence rates, and adjusted hazard ratios (aHRs) using Cox regression. aHRs accounted for sex, year of CHD diagnosis, parental mental health, and socioeconomic status. All estimates were stratified by age, sex, and CHD complexity.<br /><b>Results</b><br />The cumulative incidence of mental health conditions by 18 years of age in the CHD cohort was 35.1% (95% CI, 34.0%-36.1%), corresponding to aHRs of 1.64 (95% CI, 1.58-1.71), 1.41 (95% CI, 1.30-1.52), and 1.02 (95% CI, 0.98-1.07) compared with the general population, sibling, and major congenital anomaly cohorts, respectively. Mental health incidence rates showed prominent peaks in early childhood and adolescence. Males and children with severe or single-ventricle CHD demonstrated higher incidence rates of mental health conditions relative to females and children with mild or moderate CHD, respectively. Compared with the general population and sibling cohorts, incidence rates and aHRs in the CHD cohort were highest for severe stress reactions, attention deficit/hyperactivity disorder, intellectual disability, and autism spectrum disorder. Compared with children in the major congenital anomaly cohort, the aHRs were close to 1.<br /><b>Conclusions</b><br />More than one-third of children with CHD were diagnosed or treated for a mental health condition by 18 years of age. Mental health conditions began early in life and were most prominent among males and children with severe or single-ventricle heart disease.<br /><br /><br /><br /><small>Circulation: 18 Sep 2023; epub ahead of print</small></div>

<div><h4>Cerebral embolic protection during transcatheter heart interventions.</h4><i>Jimenez Diaz VA, Kapadia SR, Linke A, Mylotte D, ... Settergren M, Puri R</i><br /><AbstractText>Stroke remains a devastating complication of transcatheter aortic valve replacement (TAVR), with the incidence of clinically apparent stroke seemingly fixed at around 3% despite TAVR\'s significant evolution during the past decade. Embolic showers of debris (calcium, atheroma, valve material, foreign material) are captured in the majority of patients who have TAVR using a filter-based cerebral embolic protection device (CEPD). Additionally, in systematic brain imaging studies, the majority of patients receiving TAVR exhibit new cerebral lesions. Mechanistic studies have shown reductions in the volume of new cerebral lesions using CEPDs, yet the first randomised trial powered for periprocedural stroke within 72 hours of a transfemoral TAVR failed to meet its primary endpoint of showing superiority of the SENTINEL CEPD. The present review summarises the clinicopathological rationale for the development of CEPDs, the evidence behind these devices to date and the emerging recognition of cerebral embolisation in many non-TAVR transcatheter procedures. Given the uniqueness of each of the various CEPDs under development, specific trials tailored to their designs will need to be undertaken to broaden the CEPD field, in addition to evaluating the role of CEPD in non-TAVR transcatheter heart interventions. Importantly, the cost-effectiveness of these devices will require assessment to broaden the adoption of CEPDs globally.</AbstractText><br /><br /><br /><br /><small>EuroIntervention: 18 Sep 2023; 19:549-570</small></div>

<div><h4>Adequacy of Size Matching With Predicted Heart Mass Ratio in Diverse Types of Cardiomyopathies.</h4><i>Yanagida R, Firoz A, Kashem M, Hamad E, Toyoda Y</i><br /><AbstractText>Predicted heart mass ratio (PHMr) has been proposed as an optimal size metric in the selection of a donor heart for transplant; however, it is not known if the same size matching criteria pertains uniformly to all types of cardiomyopathies. Heart transplant recipients in the United Network for Organ Sharing registry database were categorized into 6 groups based on the type of cardiomyopathy, dilated, coronary artery disease, hypertrophic, restrictive, valvular and adult congenital heart disease. Patients in each group of etiology were stratified based on the PHMr into 5 groups: severely undersized <0.86, moderately undersized 0.86 to 0.94, matched 0.95 to 1.04, moderately oversized 1.05 to 1.24, and severely oversized >1.25. The survival and cause of death of patients in each etiology group were reviewed. The United Network for Organ Sharing registry database from January 1987 to July 2021 included 53,573 patients who received a heart transplant. Compared with patients with size matched hearts, recipients with dilated (hazard ratio 1.17, p = 0.001) and valvular (hazard ratio 1.79, p = 0.032) cardiomyopathy who had an undersized heart with PHMr <0.86 had decreased survival. In addition, the survival of patients with hypertrophic or restrictive cardiomyopathy and adult congenital heart disease was not affected by size matching based on the PHMr (0.601 and 0.079, respectively, p = 0.873). In conclusion, our analysis suggests that the size matching criteria based on PHMr may not be uniform to all patients across various etiologies of cardiomyopathy. Therefore, the data can be used to increase the acceptance rate of donor hearts, particularly, for patients with hypertrophic, restrictive cardiomyopathy and congenital heart disease in which size matching is less significant for survival outcome.</AbstractText><br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 16 Sep 2023; 206:295-302</small></div>

<div><h4>Cardiovascular Events After Aortic Root Repair in Patients With Marfan Syndrome.</h4><i>David TE, Park J, Tatangelo M, Steve Fan CP, Ouzounian M</i><br /><b>Background</b><br />The usefulness of aortic valve sparing operations to treat aortic root aneurysm in patients with Marfan syndrome (MS) remains controversial.<br /><b>Objectives</b><br />The purpose of this study was to evaluate the occurrence of cardiovascular events in patients with MS who have undergone valve-preserving aortic root replacement.<br /><b>Methods</b><br />Patients with MS who had aortic valve sparing operations (reimplantation of the aortic valve or remodeling of the aortic root) from 1988 through 2019 were followed prospectively for a median of 14 years. Pertinent data from clinical, echocardiographic, computed tomography, and magnetic resonance images of the aorta were collected and analyzed.<br /><b>Results</b><br />There were 189 patients whose mean age was 36 years, and 67% were men. Ten patients presented with acute type A dissection and 29 had mitral regurgitation. There were 52 patients at risk at 20 years. Mortality rate at 20 years was 21.5% (95% CI: 14.7%-30.8%); advancing age and preoperative aortic dissections were associated with increased risk of death by multivariable analysis. At 20 years, the cumulative incidence of moderate or severe aortic insufficiency was 14.5% (95% CI: 9.5%-22.0%), reoperation on the aortic valve was 7.5% (95% CI: 3.9%-14.7%), and new distal aortic dissections was 19.9% (95% CI: 13.9%-28.5%). Remodeling of aortic root was associated with greater risk of developing aortic insufficiency and aortic valve reoperation than reimplantation of the aortic valve.<br /><b>Conclusions</b><br />Aortic valve sparing operations provide stable aortic valve function and low rates of valve-related complications during the first 2 decades of follow-up but aortic dissections remain problematic in patients with MS.<br /><br />Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 12 Sep 2023; 82:1068-1076</small></div>

<div><h4>Left Atrial Strain and Incident Atrial Fibrillation in Older Adults.</h4><i>Mannina C, Ito K, Jin Z, Yoshida Y, ... Homma S, Di Tullio MR</i><br /><AbstractText>Atrial fibrillation (AF) is frequent in older adults and associated with left atrial (LA) dysfunction. LA strain (LAε) and LA strain rate (LASR) may detect subclinical LA disease. We investigated whether reduced LAε and LASR predict new-onset AF in older adults without history of AF or stroke. LAε and LASR were assessed by speckle-tracking echocardiography in 824 participants from the community-based Cardiovascular Abnormalities and Brain Lesions study. Positive longitudinal LAε and LASR during ventricular systole, LASR during early ventricular diastole, and LASR during LA contraction were measured. Cause-specific hazards regression model evaluated the association of LAε and LASR with incident AF, adjusting for pertinent covariates. The mean age was 71.1 ± 9.2 years (313 men, 511 women). During a mean follow-up of 10.9 years, new-onset AF occurred in 105 participants (12.7%). Lower LAε and LASR at baseline were observed in patients with new-onset AF (all p <0.01). In multivariable analysis, positive longitudinal LAε (adjusted hazard ratio [HR] per SD decrease 2.05, confidence interval [CI] 1.24 to 3.36) and LASR during LA contraction (HR per SD increase 2.24, CI 1.37 to 3.65) remained associated with new-onset AF, independently of LA volumes and left ventricular function. Along with positive longitudinal LAε, reduced LASR during ventricular systole predicted AF in participants with LA volume below the median value (HR 2.54, CI 1.10 to 6.09), whereas reduced LASR during LA contraction predicted AF in participants with larger LA (HR 2.35, CI 1.31 to 4.23). In conclusion, reduced positive longitudinal LAε and LASR predict new-onset AF in older adults regardless of LA size and may improve AF risk stratification.</AbstractText><br /><br />Copyright © 2023 Elsevier Inc. All rights reserved.<br /><br /><small>Am J Cardiol: 12 Sep 2023; 206:161-167</small></div>

<div><h4>Mechanisms of benefits of sodium-glucose cotransporter 2 inhibitors in heart failure with preserved ejection fraction.</h4><i>Pandey AK, Bhatt DL, Pandey A, Marx N, ... Pandey A, Verma S</i><br /><AbstractText>For decades, heart failure with preserved ejection fraction (HFpEF) proved an elusive entity to treat. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently been shown to reduce the composite of heart failure hospitalization or cardiovascular death in patients with HFpEF in the landmark DELIVER and EMPEROR-Preserved trials. While improvements in blood sugar, blood pressure, and attenuation of kidney disease progression all may play some role, preclinical and translational research have identified additional mechanisms of these agents. The SGLT2 inhibitors have intriguingly been shown to induce a nutrient-deprivation and hypoxic-like transcriptional paradigm, with increased ketosis, erythropoietin, and autophagic flux in addition to altering iron homeostasis, which may contribute to improved cardiac energetics and function. These agents also reduce epicardial adipose tissue and alter adipokine signalling, which may play a role in the reductions in inflammation and oxidative stress observed with SGLT2 inhibition. Emerging evidence also indicates that these drugs impact cardiomyocyte ionic homeostasis although whether this is through indirect mechanisms or via direct, off-target effects on other ion channels has yet to be clearly characterized. Finally, SGLT2 inhibitors have been shown to reduce myofilament stiffness as well as extracellular matrix remodelling/fibrosis in the heart, improving diastolic function. The SGLT2 inhibitors have established themselves as robust, disease-modifying therapies and as recent trial results are incorporated into clinical guidelines, will likely become foundational in the therapy of HFpEF.</AbstractText><br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 07 Sep 2023; epub ahead of print</small></div>

<div><h4>Phase 3 Trial of Concizumab in Hemophilia with Inhibitors.</h4><i>Matsushita T, Shapiro A, Abraham A, Angchaisuksiri P, ... Jiménez-Yuste V, explorer7 Investigators</i><br /><b>Background</b><br />Concizumab is an anti-tissue factor pathway inhibitor monoclonal antibody designed to achieve hemostasis in all hemophilia types, with subcutaneous administration. A previous trial of concizumab (explorer4) established proof of concept in patients with hemophilia A or B with inhibitors.<br /><b>Methods</b><br />We conducted the explorer7 trial to assess the safety and efficacy of concizumab in patients with hemophilia A or B with inhibitors. Patients were randomly assigned in a 1:2 ratio to receive no prophylaxis for at least 24 weeks (group 1) or concizumab prophylaxis for at least 32 weeks (group 2) or were nonrandomly assigned to receive concizumab prophylaxis for at least 24 weeks (groups 3 and 4). After a treatment pause due to nonfatal thromboembolic events in three patients receiving concizumab, including one from the explorer7 trial, concizumab therapy was restarted with a loading dose of 1.0 mg per kilogram of body weight, followed by 0.2 mg per kilogram daily (potentially adjusted on the basis of concizumab plasma concentration as measured at week 4). The primary end-point analysis compared treated spontaneous and traumatic bleeding episodes in group 1 and group 2. Safety, patient-reported outcomes, and pharmacokinetics and pharmacodynamics were also assessed.<br /><b>Results</b><br />Of 133 enrolled patients, 19 were randomly assigned to group 1 and 33 to group 2; the remaining 81 were assigned to groups 3 and 4. The estimated mean annualized bleeding rate in group 1 was 11.8 episodes (95% confidence interval [CI], 7.0 to 19.9), as compared with 1.7 episodes (95% CI, 1.0 to 2.9) in group 2 (rate ratio, 0.14 [95% CI, 0.07 to 0.29]; P<0.001). The overall median annualized bleeding rate for patients receiving concizumab (groups 2, 3, and 4) was 0 episodes. No thromboembolic events were reported after concizumab therapy was restarted. The plasma concentrations of concizumab remained stable over time.<br /><b>Conclusions</b><br />Among patients with hemophilia A or B with inhibitors, the annualized bleeding rate was lower with concizumab prophylaxis than with no prophylaxis. (Funded by Novo Nordisk; explorer7 ClinicalTrials.gov number, NCT04083781.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 31 Aug 2023; 389:783-794</small></div>

<div><h4>Stroke risk in women with atrial fibrillation.</h4><i>Buhari H, Fang J, Han L, Austin PC, ... Lee DS, Abdel-Qadir H</i><br /><b>Background:</b><br/>and aims</b><br />Female sex is associated with higher rates of stroke in atrial fibrillation (AF) after adjustment for other CHA2DS2-VASc factors. This study aimed to describe sex differences in age and cardiovascular care to examine their relationship with stroke hazard in AF.<br /><b>Methods</b><br />Population-based cohort study using administrative datasets of people aged ≥66 years diagnosed with AF in Ontario between 2007 and 2019. Cause-specific hazard regression was used to estimate the adjusted hazard ratio (HR) for stroke associated with female sex over a 2-year follow-up. Model 1 included CHA2DS2-VASc factors, with age modelled as 66-74 vs. ≥ 75 years. Model 2 treated age as a continuous variable and included an age-sex interaction term. Model 3 further accounted for multimorbidity and markers of cardiovascular care.<br /><b>Results</b><br />The cohort consisted of 354 254 individuals with AF (median age 78 years, 49.2% female). Females were more likely to be diagnosed in emergency departments and less likely to receive cardiologist assessments, statins, or LDL-C testing, with higher LDL-C levels among females than males. In Model 1, the adjusted HR for stroke associated with female sex was 1.27 (95% confidence interval 1.21-1.32). Model 2 revealed a significant age-sex interaction, such that female sex was only associated with increased stroke hazard at age >70 years. Adjusting for markers of cardiovascular care and multimorbidity further decreased the HR, so that female sex was not associated with increased stroke hazard at age ≤80 years.<br /><b>Conclusion</b><br />Older age and inequities in cardiovascular care may partly explain higher stroke rates in females with AF.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 30 Aug 2023; epub ahead of print</small></div>

<div><h4>Predictors of 5-Year Mortality in Patients Managed With a Magnetically Levitated Left Ventricular Assist Device.</h4><i>Nayak A, Hall SA, Uriel N, Goldstein DJ, ... Wang A, Mehra MR</i><br /><b>Background</b><br />In advanced heart failure patients implanted with a fully magnetically levitated HeartMate 3 (HM3, Abbott) left ventricular assist device (LVAD), it is unknown how preimplant factors and postimplant index hospitalization events influence 5-year mortality in those able to be discharged.<br /><b>Objectives</b><br />The goal was to identify risk predictors of mortality through 5 years among HM3 LVAD recipients conditional on discharge from index hospitalization in the MOMENTUM 3 pivotal trial.<br /><b>Methods</b><br />This analysis evaluated 485 of 515 (94%) patients discharged after implantation of the HM3 LVAD. Preimplant (baseline), implant surgery, and index hospitalization characteristics were analyzed individually, and as multivariable predictors for mortality risk through 5 years.<br /><b>Results</b><br />Cumulative 5-year mortality in the cohort (median age: 62 years, 80% male, 65% White, 61% destination therapy due to transplant ineligibility) was 38%. Two preimplant characteristics (elevated blood urea nitrogen and prior coronary artery bypass graft or valve procedure) and 3 postimplant characteristics (hemocompatibility-related adverse events, ventricular arrhythmias, and estimated glomerular filtration rate <60 mL/min/1.73 m<sup>2</sup> at discharge) were predictors of 5-year mortality. In 171 of 485 patients (35.3%) without any risk predictors, 5-year mortality was reduced to 22.6% (95% CI: 15.4%-32.7%). Even among those with 1 or more predictors, mortality was <50% at 5 years (45.7% [95% CI: 39.0%-52.8%]).<br /><b>Conclusions</b><br />Long-term survival in successfully discharged HM3 LVAD recipients is largely influenced by clinical events experienced during the index surgical hospitalization in tandem with baseline factors, with mortality of <50% at 5 years. In patients without identified predictors of risk, long-term 5-year mortality is low and rivals that achieved with heart transplantation, even though most were implanted with destination therapy intent. (MOMENTUM 3 IDE Clinical Study Protocol, NCT02224755; MOMENTUM 3 Pivotal Cohort Extended Follow-up PAS, NCT03982979).<br /><br />Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.<br /><br /><small>J Am Coll Cardiol: 29 Aug 2023; 82:771-781</small></div>

<div><h4>Atrial pacing minimization in sinus node dysfunction and risk of incident atrial fibrillation: a randomized trial.</h4><i>Kronborg MB, Frausing MHJP, Malczynski J, Riahi S, ... Nielsen JC, DANPACE II Investigators </i><br /><b>Background:</b><br/>and aims</b><br />High percentages of atrial pacing have been associated with an increased risk of atrial fibrillation. This study aimed at evaluating whether atrial pacing minimization in patients with sinus node dysfunction reduces the incidence of atrial fibrillation.<br /><b>Methods</b><br />In a nationwide, randomized controlled trial, 540 patients with sinus node dysfunction and an indication for first pacemaker implantation were assigned to pacing programmed to a base rate of 60 bpm and rate-adaptive pacing (DDDR-60) or pacing programmed to a base rate of 40 bpm without rate-adaptive pacing (DDD-40). Patients were followed on remote monitoring for 2 years. The primary endpoint was time to first episode of atrial fibrillation longer than 6 min. Secondary endpoints included longer episodes of atrial fibrillation, and the safety endpoint comprised a composite of syncope or presyncope.<br /><b>Results</b><br />The median percentage of atrial pacing was 1% in patients assigned to DDD-40 and 49% in patients assigned to DDDR-60. The primary endpoint occurred in 124 patients (46%) in each treatment group (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.76-1.25, P=0.83). There were no between-group differences in atrial fibrillation exceeding 6- or 24 hours, persistent atrial fibrillation, or cardioversions for atrial fibrillation. The incidence of syncope or presyncope was higher in patients assigned to DDD-40 (HR 1.71 95% CI 1.13-2.59, P=0.01).<br /><b>Conclusions</b><br />Atrial pacing minimization in patients with sinus node dysfunction does not reduce the incidence of atrial fibrillation. Programming a base rate of 40 bpm without rate-adaptive pacing is associated with an increased risk of syncope or presyncope.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 28 Aug 2023; epub ahead of print</small></div>

<div><h4>Prevalence and Incidence of Diastolic Dysfunction in Atrial Fibrillation: Clinical Implications.</h4><i>Naser JA, Lee E, Scott CG, Kennedy AM, ... Pislaru SV, Borlaug BA</i><br /><b>Background:</b><br/>and aims</b><br />Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are intimately associated disorders. HFpEF may be overlooked in AF when symptoms are simply attributed to dysrhythmia, and incident AF may identify patients at risk for developing diastolic dysfunction (DD). This study aimed to investigate the prevalence and incidence of DD in patients with new-onset AF compared to sinus rhythm (SR).<br /><b>Methods</b><br />Adults with new-onset AF (n = 1,747) or SR (n = 29,623) and no structural heart disease were identified. Propensity-score matching was performed (1:3 ratio) between AF and SR based on age, sex, body mass index, and comorbidities. Severe DD (SDD) was defined by ≥3/4 abnormal parameters (medial e\', medial E/e\', tricuspid regurgitation velocity, left atrial volume index) and ≥moderate (MDD) by ≥2/4. Annualised changes in DD indices were determined.<br /><b>Results</b><br />New-onset AF was independently associated with SDD (8% vs 3%) and ≥MDD (25% vs 16%). 62% of patients with AF had high-risk H2FPEF scores and 5% had clinically-recognised HFpEF. Over a median follow-up of 3.2 (interquartile range 1.6-5.8) years, DD progressed 2-4-fold more rapidly in those with new-onset AF (p < 0.001 for all). Risk for incident DD was increased i new-onset AF [hazard ratio (95% confidence interval) 2.69 (2.19-3.32) for SDD and 1.73 (1.49-2.02) for ≥MDD].<br /><b>Conclusions</b><br />Patients with new-onset AF display high-risk features for HFpEF at diagnosis, emphasizing the importance of evaluating for HFpEF among symptomatic patients with AF. Patients with new-onset AF have accelerated progression in DD over time, which may identify patients with preclinical HFpEF, where preventive therapies may be tested.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 28 Aug 2023; epub ahead of print</small></div>

<div><h4>Catheter Ablation in End-Stage Heart Failure with Atrial Fibrillation.</h4><i>Sohns C, Fox H, Marrouche NF, Crijns HJGM, ... Sommer P, CASTLE HTx Investigators</i><br /><b>Background</b><br />The role of catheter ablation in patients with symptomatic atrial fibrillation and end-stage heart failure is unknown.<br /><b>Methods</b><br />We conducted a single-center, open-label trial in Germany that involved patients with symptomatic atrial fibrillation and end-stage heart failure who were referred for heart transplantation evaluation. Patients were assigned to receive catheter ablation and guideline-directed medical therapy or medical therapy alone. The primary end point was a composite of death from any cause, implantation of a left ventricular assist device, or urgent heart transplantation.<br /><b>Results</b><br />A total of 97 patients were assigned to the ablation group and 97 to the medical-therapy group. The trial was stopped for efficacy by the data and safety monitoring board 1 year after randomization was completed. Catheter ablation was performed in 81 of 97 patients (84%) in the ablation group and in 16 of 97 patients (16%) in the medical-therapy group. After a median follow-up of 18.0 months (interquartile range, 14.6 to 22.6), a primary end-point event had occurred in 8 patients (8%) in the ablation group and in 29 patients (30%) in the medical-therapy group (hazard ratio, 0.24; 95% confidence interval [CI], 0.11 to 0.52; P<0.001). Death from any cause occurred in 6 patients (6%) in the ablation group and in 19 patients (20%) in the medical-therapy group (hazard ratio, 0.29; 95% CI, 0.12 to 0.72). Procedure-related complications occurred in 3 patients in the ablation group and in 1 patient in the medical-therapy group.<br /><b>Conclusions</b><br />Among patients with atrial fibrillation and end-stage heart failure, the combination of catheter ablation and guideline-directed medical therapy was associated with a lower likelihood of a composite of death from any cause, implantation of a left ventricular assist device, or urgent heart transplantation than medical therapy alone. (Funded by Else Kröner-Fresenius-Stiftung; CASTLE-HTx ClinicalTrials.gov number, NCT04649801.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 27 Aug 2023; epub ahead of print</small></div>

<div><h4>Pulsed Field or Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation.</h4><i>Reddy VY, Gerstenfeld EP, Natale A, Whang W, ... Mansour M, ADVENT Investigators</i><br /><b>Background</b><br />Catheter-based pulmonary vein isolation is an effective treatment for paroxysmal atrial fibrillation. Pulsed field ablation, which delivers microsecond high-voltage electrical fields, may limit damage to tissues outside the myocardium. The efficacy and safety of pulsed field ablation as compared with conventional thermal ablation is not known.<br /><b>Methods</b><br />In this randomized, single-blind, noninferiority trial, we assigned patients with drug-refractory paroxysmal atrial fibrillation in a 1:1 ratio to undergo pulsed field ablation or conventional radiofrequency or cryoballoon ablation. The primary efficacy end point was freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation. The primary safety end point included acute and chronic device- and procedure-related serious adverse events.<br /><b>Results</b><br />A total of 305 patients were assigned to undergo pulsed field ablation, and 302 were assigned to undergo thermal ablation. At 1 year, the primary efficacy end point was met (i.e., no events occurred) in 204 patients (estimated probability, 73.3%) who underwent pulsed field ablation and 194 patients (estimated probability, 71.3%) who underwent thermal ablation (between-group difference, 2.0 percentage points; 95% Bayesian credible interval, -5.2 to 9.2; posterior probability of noninferiority, >0.999). Primary safety end-point events occurred in 6 patients (estimated incidence, 2.1%) who underwent pulsed field ablation and 4 patients (estimated incidence, 1.5%) who underwent thermal ablation (between-group difference, 0.6 percentage points; 95% Bayesian credible interval, -1.5 to 2.8; posterior probability of noninferiority, >0.999).<br /><b>Conclusions</b><br />Among patients with paroxysmal atrial fibrillation receiving a catheter-based therapy, pulsed field ablation was noninferior to conventional thermal ablation with respect to freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation and with respect to device- and procedure-related serious adverse events at 1 year. (Funded by Farapulse-Boston Scientific; ADVENT ClinicalTrials.gov number, NCT04612244.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 27 Aug 2023; epub ahead of print</small></div>

<div><h4>New-onset atrial fibrillation in chronic coronary syndrome: the CLARIFY registry.</h4><i>Gautier A, Picard F, Ducrocq G, Elbez Y, ... Tendera M, Steg PG</i><br /><b>Background:</b><br/>and aims</b><br />Data on new-onset atrial fibrillation (NOAF) in patients with chronic coronary syndromes (CCS) are scarce. This study aims to describe the incidence, predictors and impact on cardiovascular outcomes of NOAF in CCS patients.<br /><b>Methods</b><br />Data from the international (45 countries) CLARIFY registry (prospeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) were used. Among 29,001 CCS outpatients without previously reported AF at baseline, patients with at least one episode of AF/flutter diagnosed during 5-year follow-up were compared with patients in sinus rhythm throughout the study.<br /><b>Results</b><br />The incidence rate of NOAF was 1.12 [95% confidence interval (CI) 1.06-1.18] per 100 patient-years (cumulative incidence at 5 years: 5.0%). Independent predictors of NOAF were increasing age, increasing body mass index, low estimated glomerular filtration rate, Caucasian ethnicity, alcohol intake and low left ventricular ejection fraction, while high triglycerides were associated with lower incidence. NOAF was associated with a substantial increase in the risk of adverse outcomes, with adjusted hazard ratios of 2.01 (95% CI 1.61-2.52) for the composite of cardiovascular death, non-fatal myocardial infarction or non-fatal stroke, 2.61 (95% CI 2.04-3.34) for cardiovascular death, 1.64 (95% CI 1.07-2.50) for non-fatal myocardial infarction, 2.27 (95% CI 1.85-2.78) for all-cause death, 8.44 (95% CI 7.05-10.10) for hospitalization for heart failure and 4.46 (95% CI 2.85-6.99) for major bleeding.<br /><b>Conclusions</b><br />Among CCS patients, NOAF is common and is strongly associated with worse outcomes. Whether more intensive preventive measures and more systematic screening for AF would improve prognosis in this population deserves further investigation.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 27 Aug 2023; epub ahead of print</small></div>

<div><h4>Five-year major cardiovascular events are increased when coronary revascularization is guided by instantaneous wave-free ratio compared to fractional flow reserve: a pooled analysis of iFR-SWEDEHEART and DEFINE-FLAIR trials.</h4><i>Eftekhari A, Holck EN, Westra J, Olsen NT, ... Engstrøm T, Christiansen EH</i><br /><b>Background:</b><br/>and aims</b><br />Guidelines recommend revascularization of intermediate epicardial artery stenosis to be guided by evidence of ischemia. Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are equally recommended. Individual 5-year results of two major randomized trials comparing FFR with iFR-guided revascularization suggested increased all-cause mortality following iFR-guided revascularization. The aim of this study was a study-level meta-analysis of the 5-year outcome data in iFR-SWEDEHEART (NCT02166736) and DEFINE-FLAIR (NCT02053038).<br /><b>Methods</b><br />Composite of major adverse cardiovascular events (MACE) and its individual components [all-cause death, myocardial infarction (MI), and unplanned revascularisation] were analysed. Raw Kaplan-Meier estimates, numbers at risk and number of events were extracted at 5-year follow-up and analysed using the ipdfc package (Stata version 18, StataCorp College Station, TX USA).<br /><b>Results</b><br />In total, iFR and FFR-guided revascularization was performed in 2,254 and 2,257 patients, respectively. Revascularization was more often deferred in the iFR-group [n = 1,128 (50.0 %)] vs. the FFR-group [n = 1021 (45.2 %); p=0.001]. In the iFR-guided group the number of deaths, MACE, unplanned revascularization, and MI were 188 (8.3%), 484 (21.5%), 235 (10.4%), and 123 (5.5%) vs. 143 (6.3%), 420 (18.6%), 241 (10.7%), and 123 (5.4%) in the FFR-group. Hazard ratio [95% confidence interval (CI)] estimates for MACE were 1.18 [1.035; 1.34], all-cause mortality 1.34 [1.08; 1.67], unplanned revascularization 0.99 [0.83; 1.19], and MI 1.02 [0.80; 1.32].<br /><b>Conclusions</b><br />Five-year all-cause mortality and MACE rates were increased with revascularization guided by iFR compared to FFR. Rates of unplanned revascularization and MI were equal in the two groups.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 27 Aug 2023; epub ahead of print</small></div>

<div><h4>Coronary Flow Capacity And Survival Prediction After Revascularization: Physiological Basis And Clinical Implications.</h4><i>Gould KL, Johnson NP, Roby AE, Bui L, ... McPherson D, Narula J</i><br /><b>Background:</b><br/>and aims</b><br />Coronary Flow Capacity (CFC) associates with an Observed 10-yearsurvival probability for individual patients before and after actual revascularization for comparison to Virtual hypothetical ideal complete revascularization.<br /><b>Methods</b><br />Stress myocardial perfusion (mL/min/g) and coronary flow reserve (CFR) per pixel were quantified in 6979 coronary artery disease (CAD) subjects using Rb-82 positron emission tomography (PET) for CFC maps of artery-specific size-severity abnormalities expressed as percent left ventricle (%LV) with prospective follow-up to define survival probability per-decade as fraction of 1.0.<br /><b>Results</b><br />Severely reduced CFC in 6979 subjects predicted low survival probability that improved by 42% after revascularization compared with no revascularization for comparable severity (P=0.0015). For 283 pre-and-post-procedure PET pairs, severely reduced regional CFC-associated survival probability improved heterogeneously after revascularization (P<0.001), more so after bypass surgery than percutaneous coronary interventions (P<0.001) but normalized in only 5.7%; non-severe baseline CFC or survival probability did not improve compared with severe CFC (P=0.00001). Observed CFC=associated survival probability after actual revascularization was lower than Virtual ideal hypothetical complete post-revascularization survival probability due to residual CAD or failed revascularization (P<0.001) unrelated to gender or microvascular dysfunction. Severely reduced CFC in 2552 post-revascularization subjects associated with low survival probability also improved after repeat revascularization compared with no repeat procedures (P=0.025).<br /><b>Conclusions</b><br />Severely reduced CFC and associated Observed survival probability improved after first and repeat revascularization compared with no revascularization for comparable CFC severity. Non-severe CFC showed no benefit. Discordance between Observed actual and Virtual hypothetical post=revascularization survival probability revealed residual CAD or failed revascularization.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 27 Aug 2023; epub ahead of print</small></div>

<div><h4>Complete or Culprit-Only PCI in Older Patients with Myocardial Infarction.</h4><i>Biscaglia S, Guiducci V, Escaned J, Moreno R, ... Campo G, FIRE Trial Investigators</i><br /><b>Background</b><br />The benefit of complete revascularization in older patients (≥75 years of age) with myocardial infarction and multivessel disease remains unclear.<br /><b>Methods</b><br />In this multicenter, randomized trial, we assigned older patients with myocardial infarction and multivessel disease who were undergoing percutaneous coronary intervention (PCI) of the culprit lesion to receive either physiology-guided complete revascularization of nonculprit lesions or to receive no further revascularization. Functionally significant nonculprit lesions were identified either by pressure wire or angiography. The primary outcome was a composite of death, myocardial infarction, stroke, or any revascularization at 1 year. The key secondary outcome was a composite of cardiovascular death or myocardial infarction. Safety was assessed as a composite of contrast-associated acute kidney injury, stroke, or bleeding.<br /><b>Results</b><br />A total of 1445 patients underwent randomization (720 to receive complete revascularization and 725 to receive culprit-only revascularization). The median age of the patients was 80 years (interquartile range, 77 to 84); 528 patients (36.5%) were women, and 509 (35.2%) were admitted for ST-segment elevation myocardial infarction. A primary-outcome event occurred in 113 patients (15.7%) in the complete-revascularization group and in 152 patients (21.0%) in the culprit-only group (hazard ratio, 0.73; 95% confidence interval [CI], 0.57 to 0.93; P = 0.01). Cardiovascular death or myocardial infarction occurred in 64 patients (8.9%) in the complete-revascularization group and in 98 patients (13.5%) in the culprit-only group (hazard ratio, 0.64; 95% CI, 0.47 to 0.88). The safety outcome did not appear to differ between the groups (22.5% vs. 20.4%; P = 0.37).<br /><b>Conclusions</b><br />Among patients who were 75 years of age or older with myocardial infarction and multivessel disease, those who underwent physiology-guided complete revascularization had a lower risk of a composite of death, myocardial infarction, stroke, or ischemia-driven revascularization at 1 year than those who received culprit-lesion-only PCI. (Funded by Consorzio Futuro in Ricerca and others; FIRE ClinicalTrials.gov number, NCT03772743.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 26 Aug 2023; epub ahead of print</small></div>

<div><h4>Global Effect of Modifiable Risk Factors on Cardiovascular Disease and Mortality.</h4><i>Global Cardiovascular Risk Consortium, Magnussen C, Ojeda FM, Leong DP, ... Ziegler A, Blankenberg S</i><br /><b>Background</b><br />Five modifiable risk factors are associated with cardiovascular disease and death from any cause. Studies using individual-level data to evaluate the regional and sex-specific prevalence of the risk factors and their effect on these outcomes are lacking.<br /><b>Methods</b><br />We pooled and harmonized individual-level data from 112 cohort studies conducted in 34 countries and 8 geographic regions participating in the Global Cardiovascular Risk Consortium. We examined associations between the risk factors (body-mass index, systolic blood pressure, non-high-density lipoprotein cholesterol, current smoking, and diabetes) and incident cardiovascular disease and death from any cause using Cox regression analyses, stratified according to geographic region, age, and sex. Population-attributable fractions were estimated for the 10-year incidence of cardiovascular disease and 10-year all-cause mortality.<br /><b>Results</b><br />Among 1,518,028 participants (54.1% of whom were women) with a median age of 54.4 years, regional variations in the prevalence of the five modifiable risk factors were noted. Incident cardiovascular disease occurred in 80,596 participants during a median follow-up of 7.3 years (maximum, 47.3), and 177,369 participants died during a median follow-up of 8.7 years (maximum, 47.6). For all five risk factors combined, the aggregate global population-attributable fraction of the 10-year incidence of cardiovascular disease was 57.2% (95% confidence interval [CI], 52.4 to 62.1) among women and 52.6% (95% CI, 49.0 to 56.1) among men, and the corresponding values for 10-year all-cause mortality were 22.2% (95% CI, 16.8 to 27.5) and 19.1% (95% CI, 14.6 to 23.6).<br /><b>Conclusions</b><br />Harmonized individual-level data from a global cohort showed that 57.2% and 52.6% of cases of incident cardiovascular disease among women and men, respectively, and 22.2% and 19.1% of deaths from any cause among women and men, respectively, may be attributable to five modifiable risk factors. (Funded by the German Center for Cardiovascular Research (DZHK); ClinicalTrials.gov number, NCT05466825.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 26 Aug 2023; epub ahead of print</small></div>

<div><h4>Dipeptidyl peptidase 3 plasma levels predict cardiogenic shock and mortality in acute coronary syndromes.</h4><i>Wenzl FA, Bruno F, Kraler S, Klingenberg R, ... Räber L, Lüscher TF</i><br /><b>Background:</b><br/>and aims</b><br />Dipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of angiotensin II which disturbs peripheral blood pressure regulation and compromises left ventricular function. This study examined the relationship of circulating DPP3 (cDPP3) with cardiogenic shock (CS) and mortality in patients presenting with acute coronary syndromes (ACS).<br /><b>Methods</b><br />Plasma cDPP3 levels were assessed at baseline and 12-24 hours after presentation in patients with ACS prospectively enrolled into the multicentre SPUM-ACS study (n = 4787).<br /><b>Results</b><br />Circulating DPP3 levels were associated with in-hospital CS when accounting for established risk factors including the ORBI risk score (per log-2 increase, hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.05-1.82, P = 0.021). High cDPP3 was as an independent predictor of mortality at 30 days (HR 1.87, 95% CI 1.36-2.58, P < 0.001) and at 1 year (HR 1.61, 95% CI 1.28-2.02, P < 0.001) after adjustment for established risk factors and the GRACE 2.0 score. Compared to values within the normal range, persistently elevated cDPP3 levels at 12-24 hours were associated with 13.4-fold increased 30-day mortality risk (HR 13.42, 95% CI 4.86-37.09, P < 0.001) and 5.8-fold increased 1-year mortality risk (HR 5.79, 95% CI 2.70-12.42, P < 0.001). Results were consistent across various patient subgroups.<br /><b>Conclusions</b><br />This study identifies cDPP3 as a novel marker of CS and increased mortality in patients with ACS. Circulating DPP3 offers prognostic information beyond established risk factors and improves early risk assessment.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.<br /><br /><small>Eur Heart J: 26 Aug 2023; epub ahead of print</small></div>

<div><h4>Ferric Carboxymaltose in Heart Failure with Iron Deficiency.</h4><i>Mentz RJ, Garg J, Rockhold FW, Butler J, ... Hernandez AF, HEART-FID Investigators</i><br /><b>Background</b><br />Ferric carboxymaltose therapy reduces symptoms and improves quality of life in patients who have heart failure with a reduced ejection fraction and iron deficiency. Additional evidence about the effects of ferric carboxymaltose on clinical events is needed.<br /><b>Methods</b><br />In this double-blind, randomized trial, we assigned ambulatory patients with heart failure, a left ventricular ejection fraction of 40% or less, and iron deficiency, in a 1:1 ratio, to receive intravenous ferric carboxymaltose or placebo, in addition to standard therapy for heart failure. Ferric carboxymaltose or placebo was given every 6 months as needed on the basis of iron indexes and hemoglobin levels. The primary outcome was a hierarchical composite of death within 12 months after randomization, hospitalizations for heart failure within 12 months after randomization, or change from baseline to 6 months in the 6-minute walk distance. The significance level was set at 0.01.<br /><b>Results</b><br />We enrolled 3065 patients, of whom 1532 were randomly assigned to the ferric carboxymaltose group and 1533 to the placebo group. Death by month 12 occurred in 131 patients (8.6%) in the ferric carboxymaltose group and 158 (10.3%) in the placebo group; a total of 297 and 332 hospitalizations for heart failure, respectively, occurred by month 12; and the mean (±SD) change from baseline to 6 months in the 6-minute walk distance was 8±60 and 4±59 m, respectively (Wilcoxon-Mann-Whitney P = 0.02; unmatched win ratio, 1.10; 99% confidence interval, 0.99 to 1.23). Repeated dosing of ferric carboxymaltose appeared to be safe with an acceptable adverse-event profile in the majority of patients. The number of patients with serious adverse events occurring during the treatment period was similar in the two groups (413 patients [27.0%] in the ferric carboxymaltose group and 401 [26.2%] in the placebo group).<br /><b>Conclusions</b><br />Among ambulatory patients who had heart failure with a reduced ejection fraction and iron deficiency, there was no apparent difference between ferric carboxymaltose and placebo with respect to the hierarchical composite of death, hospitalizations for heart failure, or 6-minute walk distance. (Funded by American Regent, a Daiichi Sankyo Group company; HEART-FID ClinicalTrials.gov number, NCT03037931.).<br /><br />Copyright © 2023 Massachusetts Medical Society.<br /><br /><small>N Engl J Med: 26 Aug 2023; epub ahead of print</small></div>

<div><h4>Upgrade of right ventricular pacing to cardiac resynchronisation therapy in heart failure: a randomised trial.</h4><i>Merkely B, Hatala R, Wranicz JK, Duray G, ... Kovács A, Kosztin A</i><br /><b>Background:</b><br/>and aims</b><br />De novo implanted cardiac resynchronisation therapy with defibrillator (CRT-D) reduces the risk of morbidity and mortality in patients with left bundle branch block, heart failure and reduced ejection fraction (HFrEF). However, among HFrEF patients with right ventricular pacing (RVP), the efficacy of CRT-D upgrade is uncertain.<br /><b>Methods</b><br />In this multicentre, randomised, controlled trial, 360 symptomatic (New York Heart Association class II-IVa) HFrEF patients with a pacemaker or implantable cardioverter defibrillator (ICD), high RVP burden ≥20%, and a wide, paced QRS complex duration ≥150 ms were randomly assigned to receive CRT-D upgrade (n = 215) or ICD (n = 145) in a 3:2 ratio. The primary outcome was the composite of all-cause mortality, heart failure hospitalisation or <15% reduction of left ventricular end-systolic volume assessed at 12 months. Secondary outcomes included all-cause mortality or heart failure hospitalisation.<br /><b>Results</b><br />Over a median follow-up of 12.4 months, the primary outcome occurred in 58/179 (32.4%) in the CRT-D arm vs. 101/128 (78.9%) in the ICD arm [odds ratio 0.11; 95% confidence interval (CI) 0.06-0.19; p < 0.001]. All-cause mortality or heart failure hospitalization occurred in 22/215 (10%) in the CRT-D arm vs. 46/145 (32%) in the ICD arm (hazard ratio 0.27; 95% CI 0.16-0.47; p < 0.001). The incidence of procedure- or device-related complications was similar between the two arms [CRT-D group 25/211 (12.3%) vs. ICD group 11/142 (7.8%)].<br /><b>Conclusions</b><br />In pacemaker or ICD patients with significant RVP burden and reduced ejection fraction, upgrade to CRT-D compared to ICD therapy reduced the combined risk of all-cause mortality, heart failure hospitalisation or absence of reverse remodelling.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 26 Aug 2023; epub ahead of print</small></div>

<div><h4>Significance of lipids, lipoproteins, and apolipoproteins during the first 14-16 months of life.</h4><i>Nielsen ST, Lytsen RM, Strandkjær N, Rasmussen IJ, ... Tybjærg-Hansen A, Frikke-Schmidt R</i><br /><b>Background:</b><br/>and aims</b><br />The aims of this study were to investigate lipid parameters during the first 14-16 months of life, to identify influential factors, and to test whether high concentrations at birth predict high concentrations at 2- and 14-16 months.<br /><b>Methods</b><br />The Copenhagen Baby Heart Study, including 13,354 umbilical cord blood samples and parallel venous blood samples from children and parents at birth (n = 444), 2 months (n = 364), and 14-16 months (n = 168), was used.<br /><b>Results</b><br />Concentrations of lipids, lipoproteins, and apolipoproteins in umbilical cord blood samples correlated highly with venous blood samples from newborns. Concentrations of low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, apolipoprotein B, and lipoprotein(a) increased stepwise from birth to 2 months to 14-16 months. Linear mixed models showed that concentrations of LDL cholesterol, non-HDL cholesterol, and lipoprotein(a) above the 80th percentile at birth were associated with significantly higher concentrations at 2 and 14-16 months. Finally, lipid concentrations differed according to sex, gestational age, birth weight, breastfeeding, and parental lipid concentrations.<br /><b>Conclusions</b><br />Lipid parameters changed during the first 14-16 months of life, and sex, gestational age, birth weight, breastfeeding, and high parental concentrations influenced concentrations. Children with high concentrations of atherogenic lipid traits at birth had higher concentrations at 2 and 14-16 months. These findings increase our knowledge of how lipid traits develop over the first 14-16 months of life and may help in deciding the optimal child age for universal familial hypercholesterolaemia screening.<br /><br />© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.<br /><br /><small>Eur Heart J: 26 Aug 2023; epub ahead of print</small></div>