European heart journal open最新文献

Chronic unresolved inflammation is a major driver for the genesis of cardiovascular disease, originating from unhealthy lifestyle interactions with a network of metabolic genes impacting overall immune fitness. Acute inflammation is a host defence response overlapping with safe clearance of inflammation, termed as resolution of inflammation, co-ordinated by nutritionally originated fatty acid's interaction with immune-responsive enzymes. Especially processing of polyunsaturated fatty acids by immune-responsive lipoxygenase and cyclooxygenase orchestrates the biosynthesis of specialized proresolving mediators. In contrast, dysregulation due to an imbalanced lifestyle, such as an unhealthy diet, lack of sleep, and exercise/low physical activity, drives non-resolving inflammation. Overall, the quality of fatty acids, enzymatic processing, on-time biosynthesis of SPMs, and precise activation of SPM-specific receptors operate cardiac repair in heart failure with reduced ejection fraction; however, the dysfunction of specific receptors, such as FPR2, drives obesogenic ageing and heart failure with preserved ejection fraction. Thus, the overlapping inflammation-resolution signalling pathways that are essential for cardiac repair and the prevention of cardiac damage are highly relevant to cardiometabolic disorders and the subsequent development of heart failure. Therefore, future research is warranted to study lifestyle factors that maintain the balance of inflammation-resolution signalling in cardiac health and develop new therapeutic targets for resolution medicine.

Aims: Cardiovascular-kidney-metabolic (CKM) syndrome is a novel disease concept; however, sex differences in its progression remain uncertain. This study aimed to quantify the risk of cardiovascular disease (CVD) events across CKM stages and to explore sex differences in this association.

Methods and results: We included 1 332 436 individuals (581 423 males and 751 013 females) from the DeSC database between 2014 and 2023 who had no prior CVD (i.e. CKM Stage 4). CKM stages were categorized as follows: Stage 0 (no CKM risk factors); Stage 1 (excess or dysfunctional adiposity); Stage 2 [metabolic risk factors and chronic kidney diseases (CKD)], and Stage 3 (subclinical CVD). We used Cox models to examine the association of CKM stages with the risk of CVD events (newly developed CKM Stage 4), including myocardial infarction, stroke, heart failure, atrial fibrillation, and peripheral artery disease. The progression from CKM Stages 0 to 3 showed a dose-dependent increase in adjusted hazard ratios (HR) for developing CVD events, with the highest risk at Stage 3 [1.85 (95% CI: 1.80-1.90)]. A similar pattern was observed in both males and females. However, the magnitude of associations for CKM stages 1-3 differed between the sexes: HR by Stage 1, 1.12 (1.04-1.21) vs. 1.12 (1.07-1.16); by Stage 2, 1.78 (1.69-1.88) vs. 1.43 (1.39-1.48); by Stage 3, 1.99 (1.89-2.10) vs. 1.82 (1.76-1.88); and P-for-interaction values were 0.87, < 0.001, and 0.005, respectively.

Conclusion: In this large nationwide cohort, CKM stage progression was associated with higher CVD risk in both sexes, with modest sex-specific differences. These findings highlight the value of CKM staging for early risk assessment, regardless of sex.

In vitro gene editing using isogenic pairs of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) has demonstrated the feasibility of introducing or correcting specific pathogenic variants. These successes represent a key first step towards therapeutic genome editing for cardiomyopathies, showing that precise, variant-specific interventions are achievable. To translate in vitro findings to the clinic, it is essential to develop robust disease models that yield meaningful, translatable data. The next challenge is systematically identifying disease-causing variants amenable to gene editing with strong pre-clinical support. Therefore, we conducted a systematic search of published studies on isogenic hiPSC-CM pairs in cardiomyopathy research with specific criteria, including (likely) pathogenic variants causing cardiomyopathy, correction and/or introduction of variants, differentiation into CMs, and functional follow-up. We systematically assessed 785 papers and highlighted 101 studies meeting our inclusion criteria reporting 69 patients carrying 56 unique variants across 31 genes, most commonly MYH7, MYBPC3, and DMD. This expanded to 91 variants across 38 genes upon inclusion of the introduced variants in a donor line. However, reported clinical data were often incomplete, underscoring the need for standardized phenotypic documentation. We reveal a lack of patient details, which creates an incomplete picture of underlying disease variables that hinder the design of targeted personalized treatments. Omitted key clinical data can lead to misinterpretations or overlooked variables that impact treatment outcomes. This systematic review integrates current evidence from successful in vitro studies using isogenic hiPSC-CM models and proposes a reporting framework for variant prioritization and the rigorous application of isogenic controls in cardiomyopathy research.

Aims: The role of pericoronary adipose tissue (PCAT) inflammation in coronary collateral circulation (CCC) development remains unclear. This study compared PCAT characteristics in chronic total occlusion (CTO) patients with good vs. poor collaterals.

Methods and results: Twenty left anterior descending CTO patients were stratified into poor (P-CCC, n = 8) and good collateral (G-CCC, n = 12) groups per Rentrop classification. CT-derived fat attenuation index (FAI), epicardial adipose tissue (EAT) volume, and histologic markers (macrophage polarization, microvascular density) were analyzed. Compared with the P-CCC group, the G-CCC group exhibited significantly lower FAI (-93.6 ± 7.2 vs. -70.8 ± 2.4 HU, P < 0.05) but higher EAT volume [8491.3 (7951.6-13060.0) vs. 3452.8 (1741.7-6425.4) mm³, P < 0.05]. Histologically, relative to P-CCC PCAT, G-CCC PCAT showed increased M2 macrophage density (14.47 ± 2.87 vs. 3.47 ± 1.63, P < 0.05), a higher M2/M1 ratio (4.40 ± 2.17 vs. 0.95 ± 0.61, P < 0.05), and greater microvascular density (4.69 ± 1.11 vs. 2.21 ± 0.50, P < 0.05).

Conclusion: PCAT inflammation is associated with enhanced collateral vessel formation. These findings highlight PCAT's potential as a therapeutic target for collateral promotion, warranting further investigation into its molecular mechanisms.

Aims: International guidelines recommend specific antithrombotic strategies for acute myocardial infarction (AMI) patients undergoing percutaneous coronary intervention (PCI). However, real-world practice often diverges. This study aimed to assess antithrombotic therapy use in AMI patients admitted to cardiac care units (CCUs) across Italy.

Methods and results: The EmploYEd Antithrombotic Therapies in Patients with Acute Coronary Syndromes Hospitalized in Italian Cardiac Care Units (EYESHOT-2) registry (NCT06316128) is an Italian nationwide, prospective study evaluating AMI management, focusing primarily on PCI-treated patients. Between 1 and 29 February 2024, 2806 patients were enrolled across 183 Italian CCUs. Percutaneous coronary intervention was performed in 83.5% of cases, while 16.5% received conservative treatment. Patients not undergoing PCI were older, more often female, had more comorbidities, and were more frequently diagnosed with NSTEMI. Pre-treatment with dual antiplatelet therapy before angiography was administered in 58.4% of PCI-treated patients. In the cath lab, most received oral P2Y₁₂ inhibitors post-procedure. In-hospital outcomes favoured PCI, with lower rates of mortality, re-infarction, and major bleeding. Independent predictors of in-hospital bleeding among PCI patients included older age [odds ratio (OR) 1.05, 95% confidence interval (CI) 1.03-1.07, P < 0.0001], prior bleeding (OR 2.38, 95% CI 1.02-5.59, P = 0.046), recent surgery (OR 3.47, 95% CI 1.28-9.42, P = 0.01), Killip class III/IV (OR 1.75, 95% CI 1.00-3.05, P = 0.049), and femoral access (OR 2.85, 95% CI 1.80-4.49, P < 0.0001), while, among patients treated conservatively, included history of anaemia (OR 4.83, 95% CI 2.24-10.41, P < 0.0001) and peripheral vascular disease (OR 2.75, 95% 1.24-6.12, P = 0.01).

Conclusion: This nationwide registry highlights improvements in AMI care in Italy but reveals persistent discrepancies between guideline-recommended and actual practice, underscoring the need for broader adoption of evidence-based strategies.

Registration: URL: http://www.clinicaltrials.gov. NCT06316128.

Aims: P-glycoprotein (P-gp), an efflux transporter with diverse compound effects, is a vital part of cardiac function. To determine if the selective substrate tracer [¹⁸F]MC225 also functions in cardiac P-gp, micro-engineered heart tissues (µ-EHTs) utilizing human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes were used. This model offers advantages in potentially reducing animal experiments and allowing direct evaluation on human cells. However, its adoption in nuclear medicine remains very limited. This study aims to evaluate [¹⁸F]MC225 as a measurement method for cardiac P-gp function using a heart-on-chip model.

Methods and results: µ-EHTs were treated with the P-gp inhibitor Tariquidar (200 nM for 30 min) or the P-gp inducer Doxorubicin (1 µM for 24 h) and incubated with [¹⁸F]MC225 (1 MBq/mL for 30 min). First, we identified and confirmed the expression of P-gp in the µ-EHTs using immunofluorescent staining, which showed an increase of P-gp expression after Doxorubicin treatment. According to γ-counter measurements, Tariquidar-treated tissues exhibited a higher uptake (117.5 ± 33.67%, n = 24) (P = 0.035) than the control, compared to Doxorubicin-treated tissues which exhibited a lower uptake (63.97 ± 21.89%, n = 20) (P < 0.001) compared to its controls. Autoradiography visualized radioactive distribution in each µ-EHT and confirmed the γ-counter measurements.

Conclusion: [¹⁸F]MC225 effectively evaluates and measures cardiac P-gp function in µ-EHTs on the heart-on-chip platform. This research sets the stage for future studies using P-gp function to evaluate the efficacy and safety of novel cardiovascular drugs using µ-EHTs.

Aims: Catheter ablation (CA) is widely used for atrial fibrillation (AF), but pulmonary vein isolation (PVI) alone is less effective in persistent AF (peAF) than paroxysmal AF (PAF). Real-world data on patient selection, outcomes, and complications with PVI or PVI plus (≥1 additional line or CFAE/ganglionated plexi ablation) are limited. We examined characteristics, trends, recurrence, and complications in peAF ablations.

Methods and results: Patients with peAF undergoing first-time catheter ablation between 2010 and 2020 were identified from the Danish National Ablation Database. They were categorized by ablation strategy (PVI or PVI plus), and baseline characteristics and trends were assessed. AF recurrence was analysed using cumulative incidence at one and five years, and across procedural years. Major adverse cardiovascular events (MACE) and procedure-related complications were also examined. Among 4144 peAF patients, 3.417 received PVI and 727 PVI plus. Baseline characteristics were similar, except the PVI plus group had longer diagnosis-to-ablation-time (mean 5.67 years vs. 3.9 years, P < 0.001) and more severe atrial enlargement (14.8% vs. 9.8%, P < 0.001). AF recurrence was higher with PVI plus at one- and five-years (54% vs. 46%, 77% vs. 68%). Recurrence rates declined over time (2010-2013 vs. 2018-2020). PVI plus use decreased from 58% to 15%. MACE and complication rates were low and similar.

Conclusion: PVI plus was used less frequently over time and was associated with longer diagnosis-to-ablation times and larger left atria. We observed a proportional decline for both groups in AF recurrence across procedural years, and complication rates were low and similar.

Despite significant advancements in interventional cardiology, including PCI, TAVI, and other structural heart interventions, access to these life-saving procedures remains uneven across the globe. This viewpoint highlights how socioeconomic, geographic, and political disparities impact clinical decision-making, outcomes, and professional well-being. Drawing from real-world experience and health systems analysis, the article explores the multifaceted barriers that hinder equitable care-ranging from health literacy and rural access to workforce shortages and regulatory or reimbursement challenges. It further discusses the psychological burden on clinicians caused by moral distress and limited resources. Potential solutions, including telemedicine, decentralized training, public awareness campaigns, and policy advocacy, are proposed to bridge the gap and promote a more just and inclusive landscape in interventional cardiology.

Aims: Little is known about how patient frailty affects mortality and hospitalization following mitral valve intervention for mitral regurgitation (MR).

Methods and results: Using Danish nationwide registries, we identified patients undergoing first-time mitral valve intervention for MR during the period 1996-2022. Patients were categorized as frail or non-frail based on the Hospital Frailty Risk Score. We assessed 1 year mortality with the reverse Kaplan-Meier estimator, and adjusted comparisons were computed using multivariable-adjusted Cox regression analysis. A composite outcome of death or time in hospital >14 days within 1 year was examined using multivariable-adjusted logistic regression analysis. A total of 7000 patients (90.0%) were considered non-frail (median age 67.0 years, 66.3% male) and 782 (10.0%) were considered frail (median age 71.0 years, 56.3% male). One year mortality was 8.2% among non-frail patients and 13.4% among frail patients (P-value <0.0001), but no statistically significant difference was observed [hazard ratio = 1.16, 95% confidence interval (CI): 0.88-1.54, reference: non-frail patients] in the adjusted analysis. Within the first year after mitral valve intervention, 42.8% of non-frail patients were never admitted, 42.1% were admitted for 1-14 days, 6.2% for 14-28 days, and 5.1% for >28 days. Among frail patients, the corresponding proportions were 26.6%, 46.3%, 9.1%, and 9.8%. In the adjusted analysis, frail patients were associated with higher odds of the composite outcome [odds ratio = 1.65 (95% CI: 1.37-2.00)].

Conclusion: Frail patients were associated with more time spent in hospital within the first year following surgery compared with non-frail patients, but no statistically significant difference was found in the 1 year mortality according to frailty status in adjusted analysis.