Journal of the American Heart Association最新文献

Background: The role of colchicine, an anti-inflammatory agent, in improving cardiovascular outcomes in patients with recent myocardial infarction remains unclear. We sought to evaluate the efficacy and safety of colchicine compared with placebo in patients with recent myocardial infarction (within 1 month of symptom onset) at a follow-up of at least 1 year.

Methods: We systematically searched MEDLINE, Embase, and the Cochrane Library until January 2025 for randomized controlled trials comparing colchicine to placebo in recent myocardial infarction. The primary outcome was major adverse cardiovascular events (MACE; as defined by the included studies) at maximum follow-up. Secondary outcomes included individual MACE components and safety (serious adverse events [AEs], any AEs, and gastrointestinal AEs). Count data were pooled using random-effects models with inverse variance weighting to estimate risk ratios (RRs) and 95% CIs.

Results: A total of 5 randomized controlled trials were included with 6620 patients randomized to colchicine and 6625 to placebo. Most participants (79%) were male, with mean ages ranging from 59 to 61 years. Follow-up durations ranged from 1 to 3 years. At maximum follow-up, there was no statistically significant difference in MACE between colchicine and placebo (8.2% versus 9.3%; RR, 0.83 [95% CI, 0.66-1.04]). Analyses of individual MACE components were also inconclusive. Randomization to colchicine did not increase the overall incidence of AEs or serious AEs compared with placebo.

Conclusions: In patients with recent myocardial infarction, the available evidence assessing the effect of colchicine, in addition to standard therapy, on MACE remains inconclusive over a median follow-up duration of 1 year.

Background: Donor discard rates for pediatric heart transplant (HT) remain high (≈40%), often driven by concerns about elevated donor troponin levels. This study evaluated the association between peak donor troponin levels, donor troponin trends, and post transplant survival among pediatric HT recipients.

Methods: Children (aged <18 years at listing) who underwent HT between January 2007, and June 2020 were identified from the Organ Procurement and Transplantation Network registry. Recipient and donor characteristics, as well as 1-year post-HT survival, were compared across peak donor troponin I percentiles (0 to <25th, 25th to <75th, ≥75th) and troponin trend categories (increasing, persistently high, persistently low, decreasing).

Results: Among 4572 donors with reported troponin I values, 67% (n=3097) had abnormal levels. Recipients of donors with peak troponin ≥75th percentile were more frequently aged 11 to 17 years (47.1% versus 22.9% versus 33.1%), had implantable cardioverter-defibrillators (12.8% versus 5.5% versus 8.2%), and exhibited higher creatinine and bilirubin at transplant. Donors with troponin ≥75th percentile were more likely to have undergone cardiopulmonary resuscitation (63.3% versus 44.3% versus 53.7%) and had left ventricular ejection fraction ≤55% (8.7% versus 4.2% versus 6.4%) (P<0.05 for all). In adjusted analyses, peak donor troponin ≥75th percentile was associated with increased 1-year graft loss (hazard ratio, 1.22 [95% CI, 1.00-1.47]; P=0.045). Troponin trends were not associated with post-HT graft survival.

Conclusions: Most pediatric HT donors exhibit abnormal troponin levels. Elevated peak donor troponin (>0.66 ng/mL) correlates with donor hemodynamic instability and predicts worse 1-year post transplant graft survival, whereas troponin trajectories are not prognostic.

Background: The impact of endovascular thrombectomy-mediated reperfusion on malignant cerebral edema (MCE) in large-core infarction remains unclear. We assessed the reperfusion-MCE relationship and MCE's mediating role in poor outcomes.

Methods: This retrospective analysis used data from the national MAGIC (Prospective Multicenter Registry on Early Management of Acute Ischemic Stroke) registry (750 patients with large-core infarction, 38 Chinese centers, 2021-2023). MCE was defined as a midline shift of ≥5 mm on follow-up imaging within 72 hours after stroke onset. Recanalization was confirmed by computed tomography angiogram or magnetic resonance angiogram during hospitalization in the overall cohorts. Successful reperfusion was defined using the modified Treatment in Cerebral Ischemia classification 2b-3 in the endovascular thrombectomy arm. Functional outcome was 90-day modified Rankin scale score. Mediation analysis used reperfusion status as the independent variable and MCE as the mediator.

Results: Among 698 patients, (306 women [43.8%]; median age, 70 [interquartile range, 61-78] years; median, Alberta Stroke Program Early Computed Tomography] Scores, 4 [interquartile range, 2-5]), successful recanalization (adjusted odds ratio [aOR], 0.68 [95% CI, 0.47-0.99]; P=0.042) and reperfusion (aOR, 0.34 [95% CI, 0.18-0.67]; P=0.002) reduced MCE likelihood. MCE was partially responsible for worse modified Rankin Scale scores in patients without recanalization or reperfusion (MCE changed the logistic regression coefficients by 15.0% and 32.5%, respectively). Recanalization improved functional outcomes partly by mitigating MCE formation (indirect effect β=-0.10, 11.5% mediation proportion, P=0.028) in those with Alberta Stroke Program Early Computed Tomography Scores 3 to 5 but not in those with 0 to 2 (β=-0.26, P=0.140).

Conclusions: Successful reperfusion attenuates MCE formation and improves clinical outcomes in patients with large-core infarction.

Background: Black and female patients with atrial fibrillation have more strokes. Certain left atrial appendage (LAA) morphologies impose a higher stroke risk. Whether anatomic differences in LAA morphology are associated with race or sex remains unexplored.

Methods: We identified consecutive patients with computed tomography for LAA morphology and categorized each patient by self-reported race (Black versus non-Black) and sex. Each LAA morphology was assigned a score based on published relative LAA thrombus risk (lowest to highest: "chicken wing," "windsock" and "cactus," "cauliflower"). Scores and prevalence were compared across races and sexes using a Wilcoxon rank-sum test and Fisher's exact test, respectively. Logistic regression was performed to find the association of race (adjusting for sex) and sex with higher risk LAA morphologies.

Results: Among 211 patients (27% Black, n=58; 47% female, n=100), there was no difference in the projected hypothetical stroke risk across race or sex (median for Black versus non-Black patients: 1 [interquartile range, 1-4] versus 1 [interquartile range, 1-1], P=0.11; median for women versus men: 1 [interquartile range, 1-4] versus 1 [interquartile range, 1-4], P=0.62). The highest risk LAA morphology, cauliflower, had greater odds of being present in Black versus non-Black patients (unadjusted odds ratio [OR], 6.0 [1.4-25.1], P=0.049; adjusted OR, 4.8 [1.1-20.9], P=0.035). Although cauliflower LAA morphology was more prevalent in women (n=7 [9%] versus n=2 [2%] in men; P=0.063), this difference nor odds of cauliflower LAA morphology being present in women were statistically significant.

Conclusions: The highest risk LAA morphology, cauliflower, demonstrated greater odds of being present in Black patients versus non-Black patients. The difference in women versus men did not reach statistical significance. Although the study was underpowered to make the findings declarative, these results are provocative regarding the differential stroke risk across races and sexes.

Background: Fenestrated and branched endovascular aneurysm repair can be complicated by branch vessel occlusion in the absence of structural stenosis. We hypothesized that computational flow simulation could identify adverse hemodynamic features associated with postfenestrated and branched endovascular aneurysm repair branch occlusion.

Methods: Patients undergoing 4-vessel fenestrated and branched endovascular aneurysm repair for Extent II to IV thoracoabdominal aortic aneurysms were retrospectively reviewed. Branches that occluded without identifiable kinking or stenosis on computed tomography were included, along with an equal cohort of anatomy-matched patent controls. Patient-specific pulsatile rigid-wall simulations were performed using SimVascular with individualized geometries and boundary conditions. Abnormal time-averaged wall shear stress (TAWSS) was defined as <10 or >70 dynes/cm².

Results: Nine patients (36 target vessels) experienced 10 branch occlusions. Postoperative pressure and flow did not differ significantly between occluded and patent renal or mesenteric branches. However, occluded renal and mesenteric branches demonstrated significantly larger postoperative areas of abnormal TAWSS compared with controls (renal: 14.5% versus 5.9%, P=0.003; mesenteric: 17.7% versus 9.9%, P=0.035). Logistic generalized estimating equation modeling showed abnormal TAWSS to be a significant predictor of renal branch occlusion (P=0.0085). Model estimates suggested occlusion probabilities of 1.1%, 31%, and 94% at 0%, 10%, and 20% abnormal TAWSS surface area, respectively. A cluster-bootstrapped receiver operating characteristic curve (area under the curve, 0.876) identified a >10.2% threshold that correctly classified 92% of renal occlusions. Abnormal TAWSS frequently localized to distal stent-artery interfaces.

Conclusions: Elevated abnormal TAWSS within stented renal branches is associated with subsequent branch occlusion after fenestrated and branched endovascular aneurysm repair. Computational flow simulation-derived TAWSS thresholds may help identify high-risk branches before failure, warranting prospective validation.

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia with a strong genetic predisposition. Genome-wide association studies have highlighted CAV1 (caveolin 1), a caveolar protein involved in various signaling pathways, as a candidate for cardiac conduction disorders.

Methods: We explored the role of CAV1 in AF in various models to dissect possible disease mechanisms. First, CAV1 expression was examined together with the AF risk gene SHOX2 in a porcine model of induced AF. Then we screened a cohort of 282 patients with early-onset AF to identify genetic variants within CAV1 and found 1 coding and 5 noncoding variants. The coding variant was functionally investigated in zebrafish, and a comprehensive analysis panel was applied to investigate the noncoding variants.

Results: In the porcine AF model, CAV1 and SHOX2 were significantly downregulated in the right atrium and atrioventricular node. Cardiac-specific overexpression of the coding variant in zebrafish increased heart rate and caused fibrillatory waves and loss of the PR interval, supporting a pathogenic effect. Four of the 5 novel identified noncoding variants showed an association with AF and PR interval in published data sets, including 1 with genome-wide significance. The noncoding variants localized to binding sites of transcription factors EOMES, RFX5, TEAD4 and MAX. Luciferase reporter gene assays demonstrated that 3 variants significantly altered the ability of those transcription factors to activate reporter gene expression.

Conclusions: This work underscores CAV1 as an AF susceptibility gene and highlights the critical role of coding and noncoding variants in AF disease mechanisms.

Background: Right-sided heart failure (RHF), in the presence of tricuspid valve regurgitation, results from left-sided heart failure, pulmonary hypertension (PH), or heart malformations. The occurrence of RHF and tricuspid regurgitation represents a critical indicator of hospitalization rates and all-cause mortality. However, RHF has remained understudied, specifically with respect to the tricuspid valve.

Methods: Using the outbred sheep (Ovis aries) model of pulmonary artery banding that induces RHF and tricuspid regurgitation, we generated 3 batches of RNA sequencing for 354 samples containing right ventricle, left ventricle, each tricuspid and mitral valve leaflet, and the pulmonary artery representing both male and female sheep. The reads were assembled into a de novo sheep heart transcriptome for differential analysis.

Results: The de novo sheep heart transcriptome enhanced transcript mapping of reads by 43% to 45% in the heart valves relative to the reference transcriptome. Identified transcripts produce validated tissue-specific pathways in ventricles (2756 isoforms), pulmonary arteries (535 isoforms), and valves (1215 isoforms), with transcript differences between the mitral and tricuspid valve involved in extracellular and endocrine signaling. Pulmonary artery banding resulted in the most significant transcriptional changes in the tricuspid valve with alterations in endocrine and immune pathway genes.

Conclusions: This project highlights the complexity of heart valve tissues and their transcriptional activity in a sheep model of RHF. It suggests potential therapeutic interventions in heart valve remodeling in pulmonary artery hypertension, RHF, and tricuspid regurgitation. This work highlights the need for further human and model organism research into the dynamic valve cells and genes.

Background: Markers of renal function have been added to the Predicting Risk of Cardiovascular Disease Events and Systematic Coronary Risk Evaluation cardiovascular risk calculators to enhance risk prediction. Here we examine the role of estimated glomerular filtration (eGFR) and urine albumin creatinine ratio (UACR)-and related dichotomous cut points (eGFR <60 mL/minute per 1.73 m² and albuminuria ≥30 mg albumin/gram creatinine)-for prediction of coronary heart disease, cardiovascular disease (CVD) outcomes (CVD mortality, heart failure, stroke, total CVD), and total mortality, using the MESA (Multi-Ethnic Study of Athersclerosis) calculator, which includes coronary artery calcium scores as a predictor in addition to traditional CVD risk factors.

Methods: The study included 6707 participants without clinical CVD with coronary artery calcium scoring. Cox proportional hazards models, adjusted for covariates including coronary artery calcium, were used to gauge the association of UACR, eGFR, albuminuria, and eGFR<60 with outcomes and change in disease prediction by area under the curve compared with models not including renal variables. Prespecified subgroups-age, sex, race or ethnicity, diabetes-were examined.

Results: UACR and albuminuria were significantly associated with most study outcomes; eGFR and eGFR<60 were less consistently related. Albuminuria significantly increased disease prediction for heart failure and for total mortality (P<0.001) but not for other outcomes. When prespecified subgroups were examined, UACR and albuminuria significantly improved prediction for many outcomes in participants >65 years of age, and for all outcomes in participants with diabetes.

Conclusions: When coronary artery calcium is known, albuminuria improves heart failure prediction. Albuminuria and UACR each improve total mortality prediction as well. UACR and albuminuria improve prediction for all outcomes in people with diabetes.

Background: Beta blockers represent an important class of antihypertensive agents, but comparative data on different beta blockers in the treatment of hypertension remain limited. Nebivolol, a third-generation beta blocker, possesses unique pharmacological properties. This study aimed to evaluate its real-world effectiveness in blood pressure and heart rate control, as well as the associated clinical outcomes in patients with hypertension.

Methods: We conducted a retrospective review of the Chang Gung Research Database to identify patients with hypertension who were newly prescribed beta blockers-primarily nebivolol, carvedilol, and bisoprolol-between 2018 and 2023. Inverse probability of treatment weighting was applied to balance the baseline characteristics across groups. Outcomes included changes in blood pressure and heart rate, as well as the incidence of major adverse cardiovascular events.

Results: We identified 99 942 patients with hypertension. After inverse probability of treatment weighting, the patients treated with nebivolol had significantly greater reductions in systolic blood pressure (-11.0 mm Hg [95% CI, -11.6 to -10.4]), diastolic blood pressure (-8.1 mm Hg [95% CI, -8.5 to -7.6]), and heart rate (-7.3 bpm [95% CI, -7.8 to -6.9]) compared with carvedilol and other beta blockers. During a mean follow-up of 4.5 years, nebivolol use was associated with a significantly lower risk of all-cause mortality (hazard ratio [HR], 0.73 [95% CI, 0.63-0.86]) and major adverse cardiovascular events (HR, 0.81 [95% CI, 0.74-0.90]).

Conclusions: In this retrospective cohort study of patients with hypertension without heart failure, nebivolol was associated with greater reductions in blood pressure and heart rate, as well as a lower risk of all-cause mortality and major adverse cardiovascular events, compared with carvedilol and other beta blockers. Although these findings suggest potential benefits of nebivolol in this population, prospective studies are needed to validate these observations.

Background: ANGPTL8 (angiopoietin-like protein 8) regulates lipid metabolism, but its role in atherosclerosis among patients with type 2 diabetes, particularly through lipid-independent mechanisms, remains unclear.

Methods: This matched case-control study included 202 patients with type 2 diabetes (101 with atherosclerosis, and 101 without) matched for age, body mass index, and sex. Atherosclerosis was assessed via carotid intima-media thickness and plaque scores. Circulating ANGPTL8 levels were measured by ELISA. Associations were evaluated using multivariate logistic regression, restricted cubic splines, and mediation analyses.

Results: Patients with atherosclerosis had significantly higher circulating ANGPTL8 levels (529.96 [350.58-816.78] versus 470.62 [265.54-717.47] pg/mL; P=0.027). After adjusting for confounders, the highest ANGPTL8 quartile showed 3.71-fold increased atherosclerosis risk (95% CI, 1.52-9.06; P=0.004) versus the lowest quartile. Each SD increase in ANGPTL8 was associated with 56% higher risk (odds ratio, 1.56 [95% CI, 1.18-2.05]). A significant linear dose-response relationship was observed (P=0.036). Adding ANGPTL8 to traditional risk factors significantly improved discrimination (area under the curve, 0.62 [95% CI, 0.54-0.70]) and reclassification (net reclassification improvement, 0.40 [95% CI, 0.13-0.66]; P<0.001) for atherosclerosis prediction. Mediation analysis revealed that cystatin C partially mediated (8.22%) the effect of ANGPTL8 on atherosclerosis, whereas triglycerides showed negligible mediation.

Conclusions: Elevated ANGPTL8 levels are independently associated with increased atherosclerosis risk in patients with type 2 diabetes. This relationship is partially mediated through cystatin C but not lipid parameters. ANGPTL8 significantly improves cardiovascular risk prediction beyond traditional risk factors, suggesting its potential as a novel biomarker for cardiovascular risk stratification and a therapeutic target addressing residual cardiovascular risk through lipid-independent inflammatory pathways in type 2 diabetes.