Journal of the American Heart Association最新文献

Background: Lymphatic disorders such as protein-losing enteropathy, plastic bronchitis, and chylothorax are important complications of the Fontan circulation and ultimately result in an increased risk of early death. Several European centers are now performing lymphatic procedures. The aim of this study is to map the extent of these lymphatic disorders and treatments provided across European pediatric cardiology centers.

Methods and results: A survey was circulated to 49 European pediatric cardiology centers consisting of 37 questions including a mix of binary, categorical, and continuous variables. Thirty-one centers (63%) participated in the study, performing a median of 250 (interquartile range, 178 - 313) cardiopulmonary bypass procedures per year. Chylothorax emerged as the most prevalent lymphatic disorder followed by protein-losing enteropathy and plastic bronchitis. The most common diagnostic investigation method was noncontrast magnetic resonance lymphangiography (52%). Eleven centers (35%) conducted lymphatic interventions with a median of 3 (interquartile range, 1 - 4) procedures per year and 12 (interquartile range, 5 - 15) interventions in total per center.

Conclusions: This study confirms the rarity of and variation in treatment approaches for lymphatic disorders across Europe. With at least 11 centers offering lymphatic interventions, the adoption of these procedures is on the rise in Europe. To improve the quality of care and treatment outcomes for these complex patients, it is crucial to consider evidence-based lymphatic diagnostics, interventional lymphatic procedures, and the centralization of services in Europe.

Background: Pediatric hypertension is linked to environmental factors like neighborhood noise disrupting sleep, which is crucial for health. The specific interaction between noise and sleep health in causing hypertension still needs to be explored.

Methods and results: We analyzed data from 3320 participants of the ABCD (Adolescent Brain Cognitive Development) study, recruited across 21 US cities and monitored from 2018 to 2020 through 2020 to 2022. Participants with complete data on Fitbit-tracked sleep, blood pressure, height, neighborhood noise, and covariates (biological sex, race and ethnicity, pubertal stage, waist circumference) were included. Hypertension was defined as average blood pressure ≥95th percentile for age, sex, and height. Sleep health was categorized on the basis of daily duration: healthy (9-12 hours), moderately healthy (±1 hour from optimal), and low (≥1 hour deviation). Noise exposure was measured as median nighttime anthropogenic noise levels by zip code. The incidence of hypertension increased from 1.7% (95% CI, 1.4-2.1) in 2018 to 2020 to 2.9% (95% CI, 2.4-3.6) in 2020 to 2022. Adolescents with healthier sleep had a lower risk of developing hypertension (relative risk, 0.63 [95% CI, 0.25-0.82]), while no significant effects were found for neighborhood noise alone or in combination with sleep health.

Conclusions: Adequate sleep significantly reduces the risk of hypertension in adolescents, independent of environmental noise exposure. These findings underscore the importance of promoting good sleep hygiene among youth to mitigate hypertension risk.

Background: Pathological cardiac hypertrophy stands as a pivotal mechanism contributing to diverse cardiovascular diseases, ultimately leading to heart failure. Despite its clinical significance, the intricate molecular mechanisms instigating pathological cardiac hypertrophy remain inadequately understood. In this study, we aim to further reveal its complex pathogenesis by exploring the role of Fas apoptotic inhibitory molecule 2 (FAIM2) in modulating pathological cardiac hypertrophy.

Methods and results: We used phenylephrine-induced hypertrophic cardiomyocytes and also generated cardiac-specific knockout mice and adeno-associated virus serotype 9-Faim2 mice to evaluate the function of FAIM2 in pathological myocardial hypertrophy. Furthermore, unbiased RNA-sequencing analysis was used to identify the direct target and corresponding molecular events contributing to FAIM2 function. Ultimately, our study revealed a downregulation of FAIM2 expression in phenylephrine-induced hypertrophic cardiomyocytes and pressure overload-induced hypertrophic hearts. FAIM2 exhibited a significant attenuation of phenylephrine-induced enlargement of primary neonatal rat cardiomyocytes, whereas FAIM2 knockdown aggravated the hypertrophic response. Furthermore, Faim2 gene knockout significantly exacerbated cardiac hypertrophy and heart fibrosis in vivo. Mechanistic investigations unveiled that FAIM2 exerts its inhibitory effect by suppressing TAK1-JNK1/2-p38 MAPK signaling cascades, thereby mitigating cardiac hypertrophy.

Conclusions: Our findings position FAIM2 as a novel negative regulator of pathological cardiac hypertrophy through its inhibitory action on mitogen-activated protein kinase signaling activation. This identification of FAIM2's role provides crucial insights that may pave the way for the development of effective therapeutic strategies aimed at mitigating pathological cardiac hypertrophy, addressing a critical need in cardiovascular disease management.

Background: White matter hyperintensities (WMH) and their progression are associated with risk of dementia and stroke, so are an important target for clinical trials. The cost of broad magnetic resonance imaging (MRI) screening to identify eligible individuals, however, limits the feasibility of designing clinical trials targeting WMH. A low-cost retinal or clinical screening measure before MRI could reduce recruitment costs versus an MRI-only screening design in a hypothetical clinical trial.

Methods and results: Data from the Atherosclerosis Risk in Communities study with valid retinal and WMH measurements (N=1311) were used. To identify a population at greater likelihood of significant WMH on MRI and thus reduce the number of screening MRIs required, we evaluated 3 theoretical prescreening measures: (1) retinal, (2) clinical, (3) combined clinical-retinal. Given a target sample for clinical trials (N=646), we calculated screening sample sizes based on the proportion within the population having an elevated score for each prescreening measure (separately) multiplied by the proportion of significant WMH among those with that prescreening feature. Recruitment costs were calculated using estimated retinal and MRI cost estimates. Compared with the estimated cost of MRI-only screening (>$4.24 million, requiring MRI on 6526 participants), prescreening for a high clinical score resulted in total cost of $2.47 million, with an initial screening group of 52 778 participants, with MRI in 3801. A high clinical-retinal score cutoff resulted in costs of $2.9 million while requiring 13 572 participants, with 3801 completing MRI.

Conclusions: A 2-stage design with low-cost prescreening measures is a promising approach, resulting in reduced theoretical recruitment costs compared with an MRI-only design.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events. However, the precise mechanisms beyond glycemic control are not fully understood. The objective of this study was to determine the role of PDGF (platelet-derived growth factor)-related signaling in empagliflozin-mediated inhibition of neointima formation.

Methods and results: Adult male nondiabetic Wistar rats were subjected to carotid artery balloon injury. Empagliflozin (30 mg/kg per day) was administered by oral gavage for 18 days beginning 4 days before surgery. The in vitro effects of empagliflozin on rat aortic vascular smooth muscle cell (VSMC) proliferation and migration were also determined. Empagliflozin attenuated balloon injury-induced neointima formation in carotid arteries. In VSMCs, empagliflozin attenuated PDGF-BB-induced proliferation and migration. Moreover, empagliflozin-treated VSMCs did not undergo apoptosis or cytotoxic death. Empagliflozin suppressed PDGF-related signaling, including phosphorylation of PDGF receptor β, Akt, and STAT3 (signal transducer and activator of transcription 3). Overactivation of PDGF signaling attenuated empagliflozin-mediated inhibition of VSMC function. SGLT2 mRNA levels in rat VSMCs were undetectable, and SGLT2 silencing did not alter the empagliflozin-mediated effects, supporting the SGLT2-independent effects of empagliflozin on VSMC.

Conclusions: This study highlights the crucial role of suppressing PDGF-related signaling in mediating the beneficial effects of empagliflozin on neointima formation and VSMC function, which are independent of SGLT2 and glycemic control. Our study provides a novel mechanistic aspect of empagliflozin for the prevention of vascular stenosis disorders.

Background: Patent foramen ovale (PFO)-associated stroke has a complex and diverse pathogenesis. It mainly results from a paradoxical embolism caused by venous thrombosis. However, few studies have investigated the presence of an in situ thrombus in the right atrium. Transesophageal echocardiography can effectively detect right atrial septal in situ microthrombus. Therefore, we aimed to explore the relationship between a right atrial septal in situ microthrombus and PFO-associated stroke and further dissect the pathophysiological basis of microthrombus formation.

Methods and results: Between April 2022 and October 2023, we prospectively investigated 466 patients who visited our hospital for transesophageal echocardiography with a high clinical suspicion of PFO. Right atrial septal in situ microthrombus was detected in 34 patients (7%), and 23 of them were examined. The microthrombus disappeared in 13 patients and decreased in 7; PFO recanalization and anatomical variations were observed in 2 and 1 patient, respectively. The incidence of index stroke was higher in the microthrombus group than in the nonmicrothrombus group (76.47% versus 61.11%). Univariate and multivariable (adjusted) analyses revealed PFO as an independent risk factor for right atrial septal in situ microthrombus formation (odds ratio, 3.29 [95% CI, 1.49-7.26]; P=0.003).

Conclusions: Transesophageal echocardiography effectively detects right atrial septal in situ microthrombus. A PFO may promote the formation of right atrial septal in situ microthrombus. Right atrial septal in situ microthrombus significantly increases the risk of PFO-associated stroke. This finding may be crucial in disease management strategies for patients with PFO.

Background: The BIONICS (BioNIR Ridaforolimus-Eluting Coronary Stent System in Coronary Stenosis) and the NIREUS (BioNIR Ridaforolimus Eluting Coronary Stent System [BioNIR] European Angiography Study) randomized clinical trials showed noninferiority of the ridaforolimus-eluting stent (RES) compared with the zotarolimus-eluting stent (ZES) with respect to 1-year target-lesion failure and 6-month angiographic late lumen loss. We aimed to evaluate clinical outcomes between treatment groups over a 5-year follow-up.

Methods and results: Patient-level data from the BIONICS (n=1919) and NIREUS (n=302) were pooled, comparing the outcomes of patients implanted with RES and ZES. The primary end point was the 5-year rate of target-lesion failure. A total of 2221 patients (63.2±10.3 years, 79.7% men) undergoing percutaneous coronary intervention with RES (n=1159) or ZES (n=1062) were included. Most clinical and angiographic characteristics were similar between groups. At 5 years, the primary end point of target-lesion failure was similar between treatment groups (12.2% RES versus 11.3% ZES, P=0.52). Rates of TLR (7.6% RES versus 6.8% ZES, P=0.42) target-vessel-related myocardial infarction (4.8% RES versus 4.9% ZES, P=0.95) and stent thrombosis (0.9% RES versus 0.9% ZES, P=0.87) also did not differ between groups. Target-vessel revascularization and cardiac death were higher among the RES group (12.3% versus 9.5% P=0.037, and 3.6% versus 2.2% P=0.042, respectively). However, after correction for baseline characteristics, there was no significant difference in cardiac death between groups.

Conclusions: In a pooled analysis of 2 randomized trials, 5-year clinical outcomes were similar between patients undergoing percutaneous coronary intervention with RES and ZES. These results support the long-term safety and efficacy of RES for the treatment of patients with coronary artery disease.

Background: Sex differences in obesity and fat distribution may in part explain differences in cardiovascular risk in men versus women. We sought to examine sex differences in the associations of obesity and adiposity measures with cardiovascular disease-related protein biomarkers.

Methods and results: In a cross-sectional observational cohort study, we examined whether the association of obesity (body mass index [BMI] and waist circumference) and adiposity measures (visceral adipose tissue) with biomarkers demonstrates effect modification by sex using multiplicative interaction terms in multivariable linear regression models. Among 3143 participants (mean age, 50 years; 49% women), sex modified the association of BMI, waist circumference, and visceral adipose tissue with cardiovascular disease-related protein biomarkers (7 for BMI, 3 for waist circumference, and 23 for visceral adipose tissue, false discovery rate [FDR]-q_int<0.05 for all). For example, higher BMI was associated with lower α₁-microglobulin levels in men but not in women (ß, -0.113; SE, 0.028; P<0.001 in men versus ß, -0.007; SE, 0.024; P=0.78 in women). By contrast, higher BMI was associated with higher adipsin levels in men and women, but the association was more pronounced in women (ß, 0.287; SE, 0.023; P<0.001 in women versus ß, 0.189; SE, 0.026; P<0.001 in men). The associations of higher visceral adipose tissue with biomarkers representing adiposity, inflammation, and fibrosis were more pronounced in women versus men.

Conclusions: We found that sex modified the associations of obesity and adipose traits with cardiovascular risk ascertained by cardiovascular disease-related biomarkers including markers of adiposity, inflammation, and fibrosis. These findings highlight potential biological pathways that may underlie some of the observed differences in obesity-related cardiovascular disease between women and men.

Background: There is currently limited evidence comparing the association between metabolic dysfunction-associated fatty liver disease (MAFLD), nonalcoholic fatty liver disease (NAFLD), and the risk of peripheral artery disease (PAD). This study aims to analyze the associations of MAFLD and NAFLD with incident PAD.

Methods and results: Two longitudinal studies, the UKB (UK Biobank) study (n=372 216) and the ARIC (Atherosclerosis Risk in Communities) study (n=4681), categorized participants into MAFLD/non-MAFLD groups and NAFLD/non-NAFLD groups. Subsequently, participants were classified into 4 groups: non-fatty liver disease, MAFLD-only, NAFLD-only, and both MAFLD and NAFLD groups. Cox proportional hazard model estimated associations of MAFLD/NAFLD status, subtypes, and liver fibrosis severity with PAD risk. The MAFLD group had a higher risk of incident PAD compared with the non-MAFLD group, and similarly, the NAFLD group had a higher risk compared with the non-NAFLD group. Among these 4 groups, the MAFLD-only group had the strongest association with the risk of incident PAD, while the NAFLD-only group was not independently associated. Diabetic MAFLD subtype was significantly associated with increased PAD risk, and higher level of liver fibrosis scores correlated with elevated PAD risk.

Conclusions: Both MAFLD and NAFLD are significantly associated with an increased incidence of PAD, with stronger associations in MAFLD and diabetic MAFLD population. These findings emphasize that the need for screening and prevention strategies for PAD in this high-risk population is warranted. The assessment of MAFLD and its subtypes should be considered as an integral component of cardiovascular risk assessment.

Background: Work-related stress is a psychosocial risk factor linked to a higher risk of cardiovascular disease. However, the association between work-related stress and cardiovascular health (CVH) is not well established. We estimated the association between work-related stress and CVH in a multiethnic sample of adults free of cardiovascular disease at baseline.

Methods and results: We performed a cross-sectional analysis of 3579 community-based men and women, aged 45 to 84 years, of the Multi-Ethnic Study of Atherosclerosis from data collected between 2000 and 2002. Work-related stress (yes/no) was assessed by a self-administered questionnaire. CVH was measured by the American Heart Association's Life's Simple 7 metrics (smoking, physical activity, body mass index, diet, total cholesterol, blood pressure, and blood glucose). Each metric contributed 0, 1, or 2 points if in the poor, intermediate, or ideal range, respectively. The aggregated CVH score was 0 to 14 points and categorized as inadequate (0-8 points), average (9-10 points), and optimal (11-14 points). Polytomous logistic regression was used to estimate the association between work-related stress and CVH, adjusting for sociodemographic factors. The mean±SD age was 57±8 years, and 48% were women. Work-related stress was reported by 20% of participants. In fully adjusted models, participants with work-related stress had lower odds of having average (adjusted odds ratio [OR], 0.75 [95% CI, 0.62-0.92]) and optimal (adjusted OR, 0.73 [95% CI, 0.58-0.92]) CVH scores compared with participants without work-related stress.

Conclusions: Work-related stress was associated with unfavorable CVH. These findings underscore the importance of workplace psychological well-being and suggest the need for studies on interventions that may reduce work-related stress and promote CVH.