European heart journal open最新文献

Aims: Although age-related immune deterioration has been implicated as a mechanistic contributor to cardiovascular disease (CVD), evidence for an impairment of adaptive immune function in individuals with clinically verified presence of atherosclerosis is lacking.

Methods and results: To test the association between atherosclerosis and immune function, we evaluated SARS-CoV-2 vaccine responsiveness in 65- to 71-year-old individuals (n = 644) derived from a population-based cohort, characterized for subclinical atherosclerosis by coronary computed tomography angiography and carotid ultrasound. Vaccine-specific T cells were quantified by activation-induced marker assays and antibody responses by ELISA. We did not find any significant associations between the degree of subclinical atherosclerosis or history of cardiovascular disease and vaccine-specific IgG or T cells. Vaccine immunity was not associated with lipid levels but was inversely correlated with several plasma cytokines.

Conclusions: Our study demonstrates that subclinical atherosclerosis or prevalent CVD is not associated with impaired responsiveness to vaccination.

Aims: Calcific aortic stenosis (CAS) is the most common heart valvulopathy in high-income countries. There is no known treatment for CAS other than replacement of the valve in severe, symptomatic disease. Observational studies and a small openlabel randomized trial have reported that vitamin K1 supplementation may reduce the progression rate of calcification and obstruction in CAS.

Methods and results: 3PASSPORT(ACTRN12622000447752) will be a prospective, randomized, double-blind, placebo-controlled clinical trial investigating if nutritional supplementation with 10 mg of vitamin K1 can reduce the rate of valvular calcification and haemodynamic progression in CAS. Patients identified to have mild or moderate CAS based on standard echocardiographic criteria will be randomized 1:1 to vitamin K1 10 mg per day or matched placebo, and followed-up for a mean period of 16 months, ranging from 12 to 21 months. The primary endpoint will be the difference in aortic valve calcification volume, measured by computed tomography aortic valve calcium score, from baseline to follow-up, and secondary endpoints will include the change in echocardiographic progression of CAS, including peak flow velocity, mean pressure gradient, and aortic valve area. The trial is registered with the Australian New Zealand. Clinical Trials Registry (ACTRN12622000447752). The trial has met its recruitment target of 108 participants.

Conclusion: PASSPORT will be prospective, randomized, double-blind clinical trial powered to demonstrate if oral supplementation with vitamin K1 reduces the progression of valvular calcification and echocardiographic severity of disease in patients with non-severe CAS. The trial results will have implications for the management of CAS, for which there is currently no medical treatment.

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.