European heart journal open最新文献

Aims: Hypoxia-inducible factor (HIF) signalling influences cardiomyocyte differentiation, maturation, and metabolic adaptation under pathological conditions. HIF-Prolyl hydroxylase domain (HIF-PH) inhibitors, which target this pathway, have been introduced for the treatment of renal anaemia. Their precise effect or safety on cardiac function remains unclear because their pharmacokinetics and distribution are not well-understood. This study aimed to examine HIF signalling activation in adult cardiomyocytes (CMs).

Methods and results: We used tamoxifen (TAM)-inducible, CM-specific von Hippel-Lindau (VHL) knockout (VHL-MCM) mice to activate CM HIF signalling. Then we subjected the mice to normal ageing or high-fat diet (HFD) and L-NAME feeding, a murine model of heart failure with preserved ejection fraction (HFpEF). In normal ageing group, there was no difference in the echocardiographic parameters or tissue fibrosis between VHL-MCM and control mice. VHL-MCM mice exhibited significantly increased capillary density and higher expression levels of HIF-target genes (P = 0.0248, two-way ANOVA). Under HFD + L-NAME treatment, VHL-MCM mice showed transient but significantly preserved global longitudinal strain (GLS) at 12 weeks post-TAM injection compared to controls (P = 0.0284, two-way ANOVA). Sirius red staining indicated a trend towards reduced whole-heart and interstitial fibrosis with significant increase in capillary density in VHL-MCM mice.

Conclusion: Sustained HIF signalling activation in adult CM does not impair the cardiac structure and function in normal ageing process and shows transient yet beneficial effect in murine HFpEF model.

Aims: Estriol (E3) is a natural estrogen produced during pregnancy whose physiological role in the adult cardiovascular and pulmonary systems remains poorly understood. Given the established association between estrogens and obesity, our study aims to investigate the interplay between obesity, E3, and their potential cardiopulmonary effects.

Methods and results: Effect of E3 on the cardiopulmonary system was evaluated in lean and high-fat diet-induced obese mice using right heart catheterization. Plasma triglyceride and adipokines were quantified using immunological assays, and circulating E3 levels were measured via LC-MS/MS. In vitro experiments were carried out in a human adipocyte cell line and pulmonary artery smooth muscle cells (PASMCs) isolated from rats and patients with pulmonary arterial hypertension. E3 reduces visceral adipose tissue mass in vivo, primarily by attenuating adipocyte inflammation and proliferation. E3 treatment significantly reduced plasma leptin levels, contributing to improved metabolic profiles. In adipocytes, E3 reduced pro-proliferation and inflammatory markers while increasing the expression of antioxidant genes. Additionally, E3 reduced proliferation in isolated PASMCs and E3-induced signalling was observed to be mediated through the ERα receptors.

Conclusion: Our findings demonstrate, for the first time, that E3 reduces visceral adipose tissue mass, indicating its role in modulating adipose tissue characteristics while concurrently enhancing metabolic profiles. These results lay the groundwork for future research to investigate the role of E3 in disease prevention and its therapeutic application in cardiopulmonary disorders.

Aims: Left ventricular (LV) thrombus carries a high risk of death and systemic embolism. While warfarin has been the standard treatment, evidence comparing direct oral anticoagulants (DOACs) with warfarin in this setting remains limited. This study aimed to compare real-world, risk-adjusted outcomes of DOAC vs. warfarin use in patients with LV thrombus.

Methods and results: We conducted a retrospective cohort analysis using the TriNetX research network database. Adults (≥18 years) with echocardiographically confirmed LV thrombus from 2016 to 2022 were included. Patients with atrial fibrillation/flutter, venous thromboembolism, end-stage renal disease, mechanical/bioprosthetic valves, or therapy switch during follow-up were excluded. Propensity score matching (1:1) was used to balance covariates. The primary outcome was a composite of all-cause mortality and stroke/transient ischaemic attack at 30 days and 1 year. Secondary outcomes included major bleeding and LV thrombus resolution. Of 2488 eligible patients (DOAC: 950; warfarin: 1538), 945 matched pairs were analysed with all baseline covariates balanced. In the DOAC group, 74% received apixaban and 26% rivaroxaban. At 30 days and 1 year, the composite outcome did not differ significantly between DOAC and warfarin [13.3% vs. 15%; matched hazard ratio (HR): 0.90, P = 0.41, and 23.8% vs. 26.7%; matched HR: 0.93, P = 0.46, respectively]. Major bleeding rates were similar at 30 days and 1 year (1.18% vs. 1.54%; matched HR: 0.77, P = 0.54, and 4.8% vs. 4.7%; matched HR: 1.13, P = 0.58, respectively). Thrombus resolution at 6 months occurred in ∼81% of patients with follow-up imaging, with no difference by treatment group.

Conclusion: In a large propensity-matched cohort, DOACs and warfarin demonstrated comparable effectiveness and safety for LV thrombus management, supporting DOACs as a reasonable alternative.

Aims: Foetal growth restriction (FGR) and being born small for gestational age (SGA) have been linked to later cardiovascular disease. We examined the impact of FGR and SGA on neonatal echo- and electrocardiographic measurements in the Copenhagen Baby Heart Study.

Methods and results: The study included 26 175 newborns. Infants with FGR (n = 1020) and SGA (n = 2328) were compared to infants born appropriate for gestational age using linear regression with adjustment for body size, age at examination, sex, and gestational age at birth. FGR and SGA were associated with reduced left ventricular (LV) internal diameters in end-systole [adjusted mean difference (aMD) -0.09 mm, 95% confidence interval (CI) -0.18,0.01, and -0.12 mm, 95% CI -0.19, -0.06, respectively] and end-diastole (aMD -0.13 mm, 95% CI -0.24, -0.02, and -0.15 mm, 95% CI -0.22, -0.07, respectively). Exposed newborns also had thinner LV walls [interventricular septum, end-diastole: FGR -0.07 mm (95% CI: -0.11, -0.03), SGA -0.03 mm (95% CI -0.06, -0.01); LV posterior wall, end-diastole: FGR -0.05 mm (95% CI -0.09, -0.01), SGA -0.04 mm (95% CI -0.07, -0.01)]. Both groups exhibited changes in trans-mitral flow. FGR was associated with reduced right ventricular function (TAPSE aMD -0.20, 95% CI -0.31, -0.09), whereas SGA was associated with reduced LV end-diastolic (aMD -0.16, 95% CI -0.28, -0.04) and end-systolic volumes (aMD -0.08, 95% CI -0.13, -0.02) and alterations in electrocardiogram precordial leads. Both groups demonstrated reduced uncorrected QT intervals.

Conclusion: Newborns with FGR or SGA exhibited noteworthy cardiac changes, even after adjustment for body size. Follow-up studies are needed to determine the clinical significance of these findings for the later cardiovascular health.

Key question: Is inadequate foetal growth associated with subclinical changes to the infant heart that can be observed in the newborn using echo- and electrocardiography?

Key finding: Foetal growth restriction and being born small for gestational age were associated with reductions in left ventricular thickness and diameter, changes in diastolic function, and alterations in electrocardiographic parameters. Growth-restricted newborns also had altered right ventricular function.

Take-home message: Foetal growth restriction and being born small for gestational age are associated with alterations in cardiac structure and function, even after adjustment for body size and age. Follow-up examinations of these children should be considered.

Aims: Cardiac resynchronization therapy (CRT) has a class 1a indication for patients with heart failure due to reduced ejection fraction (HFrEF) who also have conduction delay. Post-CRT management pathways are uncommon. Cardiopulmonary exercise testing (CPET) provides objective functional assessments and may serve as a valuable tool in assessing CRT response and guide device optimization. This systematic review and meta-analysis aimed to assess the effect of CRT on key CPET parameters and identify patients who may benefit from further intervention.

Methods and results: A systematic search of MEDLINE, EMBASE, and Cochrane Central (May 2024) identified randomized controlled trials, non-randomized trials, and cohort studies evaluating changes in CPET post-CRT. Primary outcome was peak VO₂, with anaerobic threshold and ventilatory efficiency as secondary outcomes. Results were reported as standardized mean differences (SMD) and effect sizes using Cohen's d.

Results: Fourteen studies (12 cohort studies and 2 RCTs) involving 858 patients were included. CRT was associated with significant improvements in peak VO₂ (SMD = 0.62, 95% CI 0.19-1.05, P < 0.001), anaerobic threshold (SMD = 0.70, 95% CI 0.03-1.36, P = 0.04), and ventilatory efficiency (SMD = -0.45, 95% CI -0.68 to -0.21, P < 0.001). Considerable heterogeneity was noted, likely reflecting differences in exercise protocols, patient characteristics, and device programming.

Conclusion: CRT improves exercise capacity and ventilatory efficiency, reinforcing its physiological benefits beyond cardiac remodelling. CPET may support personalized post-CRT care, including optimization of device programming, medications, and rehabilitation. Worsening CPET parameters may help identify patients progressing to advanced heart failure, allowing for timely care planning.

Aims: Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure. With a male:female ratio of approximately 10:1, current evidence including diagnostic criteria is largely based on male-dominant collectives. Sex-specific differences may contribute to delayed diagnosis in women. This study investigates these differences in a real-world setting.

Methods and results: In this retrospective single-centre cohort study, all patients at West German Amyloidosis Center diagnosed with ATTR-CM between 2018 and 2024 were analysed. Clinical, echocardiographic, and laboratory parameters as well as outcomes under transthyretin stabilizer therapy at 6 and 12 months were evaluated. Among 240 patients, 34 (14.2%) were women. Compared to men, women had lower interventricular septal diameter, left ventricular mass, and stroke volume, but higher ejection fraction. Troponin I levels were lower and renal function was worse in women. Diagnostic delay was significantly longer in women (median 750 vs. 86 days, P = 0.022). Despite therapy, sex-specific echocardiographic differences persisted, and functional capacity remained lower in women, although NYHA functional class was comparable.

Conclusion: Transthyretin amyloid cardiomyopathy presents with persistent sex-specific differences that may contribute to diagnostic delay in women. Current diagnostic thresholds may not adequately reflect female disease patterns, underscoring the need for sex-adapted diagnostic criteria to improve early detection and management.

Aims: Vasorelaxant and anti-inflammatory properties of glucagon-like peptide-1 (GLP-1) agonists support their investigation in aiding the recovery of patients with acute pulmonary embolism (PE) at risk of worse outcomes.

Methods: We undertook a four week non-randomized, controlled open-label study examining proteomic changes, markers of vascular inflammation and exploratory imaging endpoints in response to GLP-1 agonist, semaglutide (0.25 mg weekly) added to standard of care anticoagulation in patients with intermediate high-risk PE.

Results: 44 plasma proteins were downregulated in response to semaglutide that were significantly enriched for glycoproteins (false discovery rate q < 0.01). Glycopeptide analysis of highly abundant glycoproteins between diagnosis and follow-up demonstrated a reduction in glycopeptide abundance suggesting protein deglycosylation as a possible mechanism of glycoprotein down-regulation. Down-regulated proteins included regulators of metabolic stress and complement pathway intermediates, which were at higher abundance in PE patients at diagnosis compared to age and sex-matched controls without PE (all P < 0.001). Exploratory evaluation of radiological markers of right ventricular dysfunction improved from baseline to follow-up only in patients who received semaglutide (P < 0.01).

Conclusions: These findings suggest merit in wider investigation of immunometabolic changes in the plasma proteome during acute PE recovery and their potential relevance to modulation using GLP-1 agonists.

Registration: The study was registered under clinicaltrials.org (NCT06118203).

Aims: The prevalence of adults with congenital heart disease (ACHD) is rising due to improved paediatric care. In parallel, updated data on prognosis in adult life are needed.

Objectives: The aim was to calculate the standardized mortality ratio (SMR) and death rates in ACHD compared to the general population.

Methods and results: Data were obtained from the national register of congenital heart disease. The general Swedish population served as a reference. SMR was calculated as the ratio between observed and expected deaths. 9089 patients (median age 28 years, interquartile range [IQR] 20-45, 47% females) were followed for a median of 8 years (IQR 4-14). 525 deaths occurred during observation. The SMR increased by lesion complexity: atrial septal defect [1.3 (95% CI: 1.1-1.5)]; ventricular septal defect [2.0 (1.4-2.7)]; congenital aortic valve disease [2.2 (1.6-2,9)]; Ebstein's anomaly [3.2 (1.8-5.2)]; tetralogy of Fallot [3.8 (2.6-5.2)]; congenitally corrected transposition of the great arteries [5.6 (2.9-9.6)]; Eisenmenger syndrome [8.7 (5.5-13.1)]; transposition of the great arteries with a previous atrial redirection operation [12.3 (6.8-20.1)]; and Fontan physiology [22.5 (12.5-37.0)]. Calculations were also performed by severity (mild, moderate, and severe) and age by six age groups. SMR was generally higher in younger age, and the difference in mortality from the general population was estimated to be lower for older age groups. The mortality distribution and death rate per 1000 person-years have also been calculated for each lesion.

Conclusion: The mortality in ACHD remains increased compared to the general population and reflects the severity of the lesion. In higher ages, the observed mortality is more in line with the general population, probably because of survival of the least affected patients, and that few persons with severe lesions have reached advanced age.

Aims: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a recognized marker of myocardial wall stress, but its prognostic role in patients undergoing transcatheter aortic valve implantation (TAVI) remains incompletely defined. This study assessed whether NT-proBNP levels at admission and discharge - interpreted using age-specific guideline thresholds - are associated with long-term clinical outcomes post-TAVI.

Methods and results: We retrospectively analysed 683 consecutive patients who underwent successful TAVI at Magna Graecia University between 2009 and 2023. NT-proBNP was measured at both admission and discharge. Patients were stratified into low or high NT-proBNP groups based on age-adjusted cutoffs. Among 468 patients with paired measurements, four NT-proBNP trajectory groups were identified: Low-Low, Low-High, High-Low, and High-High. The primary endpoint was a composite of all-cause mortality or heart failure (HF) rehospitalization at 2 years. Multivariable Cox models were used to adjust for confounders. At admission, 41.6% of patients had elevated NT-proBNP, associated with worse echocardiographic parameters and more comorbidities. Elevated baseline NT-proBNP predicted a higher risk of the primary outcome (26.1% vs. 13.7%; HR 2.23; 95% CI, 1.51-3.28) and all-cause mortality (21.3% vs. 9.6%; HR 2.40; 95% CI, 1.52-3.79). Among patients with serial values, 34.6% had persistently elevated NT-proBNP, while only 10.7% improved. High-High and Low-High groups showed worse outcomes compared to Low-Low; High-Low patients had comparable risk to Low-Low.

Conclusion: NT-proBNP, interpreted with age-specific thresholds, is a strong independent predictor of adverse outcomes after TAVI. Serial assessment adds prognostic value and may help guide postprocedural management.

Aims: Patients with pulmonary arterial hypertension (PAH) after congenital heart disease (CHD) correction (PAH-CHDcor) are becoming the most prevalent and rapidly expanding group within PAH associated with CHD (PAH-CHD), yet data on its presentation, long-term outcomes and prognostic variables are lacking. We report on a large paediatric and adult population with PAH-CHDcor, focusing on clinical presentation and long-term survival.

Methods and results: We studied 127 PAH-CHDcor patients (mean age 21.5 ± 10.5 years; 74.8% female) diagnosed via cardiac catheterization from 2006 to 2022. The majority had post-tricuspid shunts (73.2%), with combined pre- and post-tricuspid (11.8%) and complex shunts (6.3%) less frequent. Pulmonary vascular resistance (PVR) at diagnosis averaged 13.2 ± 8.9 WU. Diagnosis occurred late (>5 years post-repair) in 43.3% of patients. Median follow-up was 4.0 (IQR 2.0-6.4) years. Kaplan-Meier estimates for survival at 3 and 5 years were 93.3% and 89.6%, respectively. Higher baseline PVR predicted mortality (HR 1.10, 95% CI 1.03-1.16, P = 0.003) and was the strongest multivariable predictor of a composite endpoint (death, heart failure hospitalization, or parenteral prostacyclin initiation; HR 1.11, 95% CI 1.05-1.18, P < 0.001). An exploratory application of a paediatric prognostic score (GOSH) showed excellent discriminative power for mortality (AUC 0.867) and the composite endpoint (AUC 0.856) at 5 years in this independent cohort.

Conclusion: Mortality and morbidity are considerable in patients with PAH-CHDcor despite modern management. Regular, careful screening of all patients with repaired CHD is essential to ensure early diagnosis and risk stratification, with proactive evidence-based treatment to improve outcomes in this expanding population.