Journal of the American Heart Association最新文献

Background: Aortic dissection (AD) is a severe cardiovascular disease with high mortality and limited treatment options. Previous studies have shown that circular RNA and ferroptosis play significant roles in various cardiovascular diseases, regulating disease progression. However, there is little research on how circular RNA regulates ferroptosis in vascular smooth muscle cells during AD progression, and the specific molecular mechanisms remain a mystery.

Methods and results: In this study, we found that circTMEM71 is downregulated in AD and angiotensin II-induced human aortic smooth muscle cells and inhibits ferroptosis. Mechanistically, circTMEM71 can bind to IGF2BP3 (insulin-like growth factor II mRNA-binding protein 3) and inhibit its degradation via the ubiquitin-mediated proteasome pathway. Additionally, IGF2BP3 can bind to FSP1 (ferroptosis suppressor protein 1) mRNA, enhancing its stability and thus suppressing cellular ferroptosis. Finally, we also confirmed that circTMEM71 can alleviate symptoms of AD in Sprague-Dawley rats through in vivo experiments, including histopathologic changes and ferroptosis.

Conclusions: In summary, our study suggested that circTMEM71 is a potential therapeutic target for AD and highlights its role in inhibiting ferroptosis in vascular smooth muscle cells.

Background: Patients with hypertrophic cardiomyopathy (HCM) were excluded from pivotal trials comparing the efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists.

Methods: Our retrospective cohort study using the TriNetX database compared adults with HCM-atrial fibrillation who initiated DOACs or vitamin K antagonists. The primary outcomes were all-cause mortality and ischemic stroke/systemic thromboembolism. Secondary outcomes included major bleeding, intracranial hemorrhage, gastrointestinal bleeding, and all-cause hospitalization. Subgroup analysis was conducted for obstructive HCM.

Results: Among 13 143 patients with HCM-atrial fibrillation (2963 matched pairs). DOAC use was associated with lower all-cause mortality (hazard ratio [HR], 0.82[ 95% CI, 0.73-0.93]; P<0.001), major bleeding (HR, 0.85 [95% CI, 0.73-0.99]; P=0.03), and intracranial hemorrhage (HR, 0.54 [95% CI, 0.36-0.79]; P=0.001) compared with vitamin K antagonists. No differences were observed in the rates of ischemic stroke (HR, 0.94 [95% CI, 0.73-1.2]; P=0.6) or the composite of stroke or systemic thromboembolism (HR, 0.87 [95% CI, 0.69-1.10]; P=0.25), gastrointestinal bleeding (HR, 0.97 [95% CI, 0.77-1.22]; P=0.82), or all-cause hospitalizations (HR, 1.07 [95% CI, 0.93-1.07]; P=0.051). In the subgroup with obstructive HCM, DOAC use was associated with a reduced risk of all-cause mortality (HR, 0.80 [95% CI, 0.66-0.99]; P=0.035) and major bleeding (HR, 0.76 [95% CI, 0.61-0.96]; P=0.02) without stroke or thromboembolic risk reduction (HR, 0.69 [95% CI, 0.47-1.01]; P=0.05).

Conclusions: Among patients with HCM-atrial fibrillation, DOACs were associated with lower mortality and bleeding risk compared with vitamin K antagonists, with no increased risk of stroke or systemic thromboembolism.

Background: Ischemic stroke in deep brain regions is commonly attributed to small vessel ischemic disease (SVID) or branch atheromatous disease (BAD). Differentiating these mechanisms is clinically important, as BAD is associated with progressive symptoms, early neurological deterioration, and poorer outcomes, whereas SVID typically follows a more stable course. Conventional imaging is limited in distinguishing these entities. High-resolution vessel wall imaging enables direct visualization of intracranial vessel wall pathology and may refine risk stratification.

Methods: We conducted a prospective, single-center study of patients with acute subcortical infarcts admitted between 2023 and 2025. Eligible patients underwent magnetic resonance imaging with high-resolution vessel wall imaging within 1 week of admission. SVID was defined as lacunar infarction without evidence of parent artery plaque or vessel wall enhancement. BAD was defined as infarction in the territory of a penetrating artery with associated parent artery enhancement. The primary outcome was differentiation of BAD from SVID based on vessel wall enhancement. Secondary outcomes included 90-day functional outcomes.

Results: Of 23 patients enrolled, 10 underwent magnetic resonance imaging with high-resolution vessel wall imaging. Vessel wall enhancement was observed in 5 patients (50%). Patients with enhancement were more often male (100% versus 40%) and had a higher prevalence of hyperlipidemia (100% versus 20%) compared with those without enhancement. Functional outcomes at 90 days were similar between the 2 groups.

Conclusions: High-resolution vessel wall imaging can identify parent artery pathology not evident on conventional imaging, helping to distinguish BAD from SVID. This differentiation is clinically meaningful, as BAD may require more intensive secondary prevention. Larger studies are needed to validate these findings.

Background: Risk assessment of patients with syncope does not consider a short PR interval despite its association with increased risk of atrial fibrillation and all-cause mortality. This study aimed to explore the association between the PR interval and all-cause mortality and recurrent syncope in patients admitted to the hospital with syncope.

Methods: We included patients with a diagnosis of syncope and an ECG recorded within 24 hours of hospital admission from the Danish Nationwide Electrocardiogram Cohort and divided patients into short (<120 ms), normal (120-200 ms), or long PR interval (>200 ms). Patients with ECG abnormalities or comorbidities influencing the PR interval or outcomes were excluded.

Results: A total of 52 038 patients were included. Adjusting for age, sex, and relevant covariates the highest hazard ratio (HR) was observed in patients with short PR interval with an HR of 1.50 (95% CI, 1.24-1.80, P<0.001). A long PR interval did not show an association with all-cause mortality (HR, 1.02 [95% CI, 0.97-1.08], P=0.3566). Adjusted 5-year cumulative incidence of all-cause mortality was 18% for short PR interval, 14% for normal PR interval, and 13% for long PR interval. Regarding recurrent syncope, a HR of 1.14 (95% CI, 1.09-1.20. P<0.001) was seen for long PR interval. Adjusted 5-year cumulative incidence of recurrent syncope was 23% in patients with a long PR interval.

Conclusion: In patients with syncope, a short PR interval was associated with higher risk of all-cause mortality; however, a long PR interval was associated with increased rate of recurrent syncope.

Background: Low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) are risk factors for atherosclerotic cardiovascular disease (ASCVD). However, the extent to which differences in RC levels affect ASCVD risk in populations with varying degrees of LDL-C elevation remains unclear. This study aimed to investigate whether RC can provide additional risk stratification value across different sexes, ages, and elevated LDL-C statuses.

Methods: This study included 12 743 elevated LDL-C participants (LDL-C ≥3.4 mmol/L) and 50 073 age- and sex-matched non-elevated LDL-C controls from the Kailuan Study. Elevated LDL-C participants were categorized by RC levels into <0.5, 0.5 to <1.0, and ≥1.0 mmol/L subgroups. Kaplan-Meier curves and Cox proportional hazards models were used to assess the relationship between RC levels and ASCVD risk across different sexes, ages, and high LDL-C statuses.

Results: During a median follow-up of 12.8 years, 1686 elevated LDL-C participants (13.2%) and 5252 non-elevated LDL-C participants (10.5%) developed ASCVD. In the borderline-high LDL-C group (3.4 ≤ LDL-C < 4.1 mmol/L), those with the lowest RC levels showed no significant risk difference compared with controls (hazard ratio [HR], 1.03 [95% CI, 0.93-1.13]), and this pattern remained consistent across different sexes and ages. In contrast, in the high LDL-C group (LDL-C ≥4.1 mmol/L), even when RC was at the lowest level, ASCVD risk remained significantly higher than that of controls (HR, 1.20 [95% CI, 1.02-1.41]).

Conclusions: In the borderline-high LDL-C population, those with the lowest RC levels showed no significant risk difference compared with controls, and this pattern remained consistent across different sexes and age subgroups. In the high LDL-C population, even when RC was at the lowest level, ASCVD risk remained significantly higher than that of controls.

Background: Neutrophil extracellular traps are released from activated neutrophils and are involved in the pathogenesis of atherosclerotic lesions, atherothrombosis, and myocardial injury. We investigated the prognostic value of circulating neutrophil extracellular trap biomarkers in patients with suspected acute coronary syndrome (ACS).

Methods: A total of 1482 patients admitted with suspected non-ST-segment elevation ACS were included and followed for a median of 4.2 years. The primary end point was a composite of death from any cause, incident myocardial infarction and hospitalization for heart failure. Secondary end points were all-cause mortality, cardiovascular death, incident myocardial infarction, hospitalization for heart failure, and new-onset atrial fibrillation. Admission blood samples were analyzed for the neutrophil extracellular trap biomarkers double-stranded DNA (dsDNA), CitH3 (citrullinated histone H3), and myeloperoxidase-DNA.

Results: A doubling of dsDNA concentration was associated with a hazard ratio (HR) of 3.11 (95% CI, 1.61-5.98, P<0.001) for the primary end point after adjusting for traditional risk factors, cardiac troponin T and N-terminal pro-B-type natriuretic peptide. DsDNA served as a prognostic marker both in patients with (adjusted HR, 5.33 [95% CI, 1.67-17.06], P=0.005) and without ACS (adjusted HR, 2.86 [95% CI, 1.30-6.28], P=0.009). In contrast, CitH3 and myeloperoxidase-DNA showed no significant prognostic value.

Conclusions: In patients with suspected ACS, dsDNA emerged as a long-term prognostic marker for a composite outcome of death, incident myocardial infarction, or heart failure hospitalization, independent of conventional risk factors. DsDNA can independently from established risk factors identify high-risk patients with and without ACS who may benefit from risk reduction.

Background: Genetic risk scores may be useful for analyzing risks for coronary artery disease (CAD). However, comparisons between restricted and genome-wide scores have been underexplored, particularly for individuals at increased risk by one score but not the other. Here, we compared restricted polygenic risk scores with 181 high-confidence genetic variants (PRS₁₈₁) and genome-wide risk scores that encompass 6.6 million single-nucleotide polymorphisms (GRS_6.6M).

Methods: Data were from the RS (Rotterdam Study; n=11 001), MESA (Multi-Ethnic Study of Atherosclerosis; n=2685), and the Sanford Health study (n=25 166). We analyzed score associations with CAD (prevalent and incident), age at onset, and lipid medication use. Combined use of both scores was also examined.

Results: There were robust associations with CAD per SD of the scores for men (PRS₁₈₁: hazard ratio [HR], 1.19 [95% CI, 1.13-1.26]; GRS_6.6M: HR, 1.32 [95% CI, 1.26-1.39]) and women (PRS₁₈₁: HR, 1.24 [95% CI, 1.16-1.32]; GRS_6.6M: HR, 1.32 [95% CI, 1.25-1.40]). PRS₁₈₁ was more strongly associated with early-onset CAD in men (β=-0.93 [95% CI, -1.36 to -0.50]) and women (β=-0.76 [95% CI, -1.31 to -0.21]). Both scores correlated with lipid medication use, but the scores were also associated with CAD among nonusers. Individuals at high risk by both scores had the highest risk and the earliest age at onset.

Conclusions: PRS₁₈₁ and GRS_6.6M appear to identify different subsets of individuals. Use of both scores together may provide better association information on CAD risk and age at onset than each score alone.

Studies have established the safety and benefits of exercise training in patients admitted with acute heart failure, yet heterogeneity in exercise delivery patterns exists. Hence, a scoping review was undertaken to map the evidence on early exercise-based interventions (early mobilization with/without exercise training) in patients recovering from acute heart failure (admission to up to 2 weeks post-hospitalization), for geographic distribution, exercise prescription, and exercise initiation time. A systematic search was conducted across 5 databases until September 2024. Studies, including protocols, providing early exercise-based intervention anytime between admission and up to 2 weeks from discharge, in any setting, were included. Data were extracted from 30 included studies, and the obtained evidence was mapped. This study uses the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-Extension for Scoping Reviews. The review included 1,54 980 participants with acute heart failure, and 26.6% (8 of 30) of the studies focused on the older adult population. Early exercise-based interventions, ie, early mobilization (n=12), exercise training (n=5), or combined (n=13), were limited to higher- (n=23) and upper-middle-income (n=6) countries and were primarily observational (n=19) in design. The median (Q1-Q3) initiation time to exercise was 3.8 days (2.8-5.5), with a dose of eight sessions (4.7-21). The intensity ranged from very low to moderate intensity, with the duration per session ranging from 10 to 60 minutes. The use of pre-specified, well-developed initiation, monitoring, and termination criteria was not common. Early exercise-based interventions were comprehensive, multi-modal, and of low-moderate intensity, initiated within 4 days of admission.

Background: Despite recent advances in pharmacotherapy, heart failure (HF) remains a major cause of hospitalization and death, particularly among aging populations. Sodium-glucose cotransporter 2 inhibitors have reduced hospitalization for HF and cardiovascular death. However, the mechanisms underlying these cardioprotective effects, particularly in the absence of diabetes, remain unclear. Therefore, we aimed to define the cardiac-specific effects of sodium-glucose cotransporter 2 inhibitors and the mechanism by which they improve HF prognoses.

Methods: We investigated the cardioprotective properties of empagliflozin in mouse models of HF induced by transverse aortic constriction. Empagliflozin was administered daily for 2 weeks, starting 2 weeks after transverse aortic constriction, and then cardiac function was evaluated.

Results: Empagliflozin preserved cardiac function and markedly reduced myocardial fibrosis and HF markers. Empagliflozin decreased cardiac C-C chemokine receptor type 2-positive macrophages, suggesting attenuated inflammation. Empagliflozin also reduced C-C motif chemokine ligand 2 expression in cardiac fibroblasts, indicating direct modulation of fibroblast behavior under mechanical stress and inhibited recruitment of proinflammatory macrophages.

Conclusions: We propose a novel antifibrotic mechanism in which empagliflozin acts directly on mechanically stressed cardiac fibroblasts to reduce chemokine signaling and macrophage-mediated inflammation. This mechanosensitive, fibroblast-targeted action might represent a paradigm shift in understanding sodium-glucose cotransporter 2 inhibitor cardioprotection and lead to new therapeutic strategies to mitigate HF progression.

Background: Cardiac troponin T is associated with mortality in heart transplantation recipients, but the association between its longitudinal measurements and clinical outcomes has not been evaluated. This study aimed to determine whether 3 parameterizations of serial hs-cTnT (high-sensitivity cardiac troponin T)-instantaneous concentration, temporal trend, and cumulative exposure-are associated with clinical outcomes in this population.

Methods: In a retrospective analysis, 222 heart transplantation recipients (median age 50 years, 86% men) who survived >30 days post transplant were included. Joint models were used to analyze the association between longitudinal hs-cTnT and the primary outcome of all-cause mortality and the secondary outcome of major adverse cardiac events.

Results: Over a median follow-up of 2.3 years, 32 deaths and 41 major adverse cardiac events occurred. Both instantaneous hs-cTnT concentration (hazard ratio [HR], 1.85 [95% CI, 1.48-2.31]; P<0.001) and cumulative hs-cTnT exposure (HR, 1.80 [95% CI, 1.38-2.37]; P<0.001) were strongly associated with mortality. The temporal trend of hs-cTnT was significantly associated with mortality after adjustment for donor and recipient factors. Similarly, instantaneous concentration and cumulative exposure were associated with major adverse cardiac events incidence (both P<0.05). In contrast, baseline hs-cTnT lost its significant association with outcomes after multivariable adjustment.

Conclusions: Longitudinally measured hs-cTnT is independently associated with mortality and major adverse cardiac events in heart transplant recipients.