Journal of the American Heart Association最新文献

Background: The constant resistance ratio (cRR) is a novel nonhyperemic pressure ratio based on piezoresistive pressure microcatheter (PMC) measurements. With repeated measurements in randomized order of PMC and pressure wire techniques, this study aimed primarily to validate the diagnostic performance of cRR compared with fractional flow reserve (FFR) in coronary lesions of 30% to 90% diameter stenosis.

Methods: SUPREME II (Sensor-Equipped Ultrathin Pressure Microcatheter Versus Pressure Wire for Physiological Measurements) was a multicenter, prospective study that included 466 patients (483 vessels) from 11 centers. All target vessels were assessed using both pressure wire and PMC separately in randomized order under resting and hyperemic conditions. The primary end point was the diagnostic accuracy of the cRR using a PMC-based FFR of ≤0.80 as the reference standard. Secondary end points included the cRR "gray zone" of the cRR-FFR hybrid strategy and the proportion of patients in whom diagnosed was achieved without vasodilator use.

Results: The optimal cRR cutoff was 0.89, which correctly classified 82.8% of the patients, with a sensitivity and specificity of 87.0% and 80.1%, respectively, and achieved an area under the curve of 0.92 with FFR_PMC as reference (area under the curve 0.90 with FFR_{pressure wire} as reference). If FFR was added for decision-making in cases of cRR values between 0.85 and 0.91, a cRR--FFR hybrid strategy achieved a 95.3% agreement with the FFR-only strategy and allowed 68.5% of the patients to not require using vasodilator.

Conclusions: In coronary stenosis of 30% to 90% diameter stenosis, cRR measurements were highly feasible. The diagnostic accuracy of cRR with FFR_PMC as reference was excellent. Further, a cRR-FFR hybrid strategy may reduce vasodilator use without compromising diagnostic accuracy.

Registration: URL: https://clinicaltrials.gov/study/NCT05417763; Unique Identifier: NCT05417763.

Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by chronic low-grade inflammation, which influences endothelial function, affecting glycocalyx integrity, barrier permeability, and cell adhesion. The role of endothelial glycocalyx shedding in the onset and progression of HFpEF remains poorly understood. Our aim was to investigate the association of glycocalyx degradation biomarkers, hyaluronan and syndecan-1, with patient characteristics and clinical outcomes in HFpEF and at population level.

Methods: Circulating hyaluronan and syndecan-1 concentrations were assessed in a population-based cohort (STANISLAS [Suivi Temporaire Annuel Non-Invasif de la Santé des Lorrains Assurés Sociaux], n=959) and a cohort with HFpEF (NETDiamond [New Targets in Diastolic Heart Failure: From Comorbidities to Personalized Medicine], n=86).

Results: Hyaluronan levels increased with age in both the population cohort and the cohort with HFpEF. Higher hyaluronan concentrations were associated in adjusted analyses with features of adverse cardiac remodeling (higher left atrial volume index and left ventricular mass index) in both cohorts and with higher peak early mitral inflow velocity/peak early diastolic mitral annular velocity in the cohort with HFpEF. Syndecan-1 was negatively associated with left ventricular mass index in the population cohort but not in the cohort with HFpEF where a positive association with features of adverse cardiac remodeling was found. In HFpEF, higher concentrations of both hyaluronan and syndecan-1 were significantly associated with increased rates of cardiovascular events.

Conclusions: Hyaluronan increases with age and is consistently associated with adverse cardiac remodeling across the spectrum of cardiovascular risk. In HFpEF, a manifestation of advanced cardiovascular disease, both hyaluronan and syndecan-1 associate with a higher risk of events. These findings suggest that glycocalyx degradation markers provide clinically relevant information across different stages of disease. Whether such markers may serve as therapeutic targets should be further explored.

Background: Immune checkpoint inhibitors (ICIs) are associated with a 3-fold risk of atherosclerotic cardiovascular disease (ASCVD). However, the biology of atherosclerosis is different among women and men, and ASCVD risk factors among women treated with an ICI are incompletely understood. This study aimed to identify factors associated with ASCVD in women following ICIs and to characterize plaque progression.

Methods: In a single-center retrospective study, clinical and cancer-related factors were compared among women treated with ICIs who did and did not experience ASCVD. Competing risk analysis estimated the effect of ICIs on cardiovascular risk. In an imaging substudy, the rate of atherosclerotic plaque progression post-treatment was compared between women and men.

Results: Among 1188 female patients treated with an ICI, 54 (5%) experienced an ASCVD with a median time to event of 174 days. Patients with ASCVD had a higher prevalence of prior myocardial infarction and coronary revascularization (15% versus 6%, P=0.007) and prior stroke (7% versus 2%, P=0.039). Competing risk analyses, adjusting for cardiovascular risk factors, revealed an almost 3-fold increased risk of post-ICI ASCVD in women with prior cardiovascular events (hazard ratio, 2.71 [95% CI, 1.24-5.95]; P=0.013). In an imaging study, the annual rate of plaque progression post-ICI was 6% for total and 7% for non-calcified plaque, with similar rates of progression observed in women and men.

Conclusions: In female patients treated with ICIs, 5% developed an ASCVD, and a history of cardiovascular events was a risk factor. In an imaging study, plaque progressed in a short time frame after ICI therapy.

Background: Fibromuscular dysplasia (FMD) is a noninflammatory arteriopathy that may result in arterial stenosis, dissection, aneurysm, and tortuosity. Data remain limited on clinical features and outcomes of patients with FMD presenting with spontaneous cervical artery dissection (SCeAD). This study aimed to describe the characteristics and long-term outcomes of this population.

Methods: We conducted a retrospective multicenter cohort study of patients diagnosed with both SCeAD and FMD at 3 US comprehensive stroke centers (2018-2023). Patients were identified through hospital records and vascular registries. Diagnosis of FMD and SCeAD was confirmed through imaging review by vascular neurologists or cardiologists. Outcomes included recurrent dissections, cardiovascular events (ischemic stroke, transient ischemic attack, myocardial infarction, subarachnoid hemorrhage) and mortality.

Results: Among 1632 patients with SCeAD, 97 (6%) had FMD diagnosis. The cohort was predominantly female (91%) and median age at FMD diagnosis was 50 years (interquartile range, 42-63). Carotid dissections were more frequent than vertebral dissections (86% versus 27%, P<0.001). Multiple dissections occurred in 32 patients (33%): 24 (75%) had bilateral dissections, 4 (13%) had recurrent dissections in the same artery, and 7 (22%) had dissections in other vascular beds including the renal, iliac, mesenteric, and coronary arteries. Younger age (odds ratio [OR], 0.945 [95% CI, 0.908-0.983]; P=0.005) and classical FMD "beading" on imaging (OR, 3.06 [95% CI, 1.28-7.36]; P=0.012) were associated with multiple dissections. Aneurysms were detected in 27%, more frequently in patients with multiple dissections (OR, 1.66 [95% CI, 1.02-2.71]; P=0.04). Most patients were discharged on single (49%) or dual (29%) antiplatelet therapy and 22% received anticoagulation with no significant differences in event rates. Over a mean follow-up of 5±2.5 years, 13% developed recurrent dissections and 28% experienced cardiovascular events. Recurrent dissections were associated with future cardiovascular events (OR, 11.56 [95% CI, 2.22-60.07]; P=0.004).

Conclusions: FMD should be considered in patients presenting with SCeAD, particularly middle-aged women with multifocal dissections and no traditional vascular risk factors. There is an increased risk of dissection recurrence, future cardiovascular events, and harboring aneurysms. These findings highlight the need for further prospective studies that can guide surveillance and management strategies for this high-risk population.

Background: Patients with atrial fibrillation (AF) remain exposed to residual thromboembolic and cardiovascular risk despite oral anticoagulation. The Atherogenic Index of Plasma (AIP) reflects atherogenic burden, but its prognostic value in anticoagulated AF is uncertain.

Methods: This prospective cohort study included consecutive outpatients with AF initiating oral anticoagulation between January 2016 and November 2021. AIP was calculated from baseline triglyceride and high-density lipoprotein cholesterol levels. Patients were stratified into low and high AIP groups using an outcome-driven cut-off. Primary outcomes were thromboembolic events and major adverse cardiovascular events. Secondary outcomes included cardiovascular and all-cause death. Associations were assessed using restricted cubic spline models and multivariable Cox regression analyses adjusted for AF-related comorbidities and concomitant therapies.

Results: Among 2535 patients (52.4% women; median age, 76 years [interquartile range, 69-82 years]) followed up for 1.81±0.50 years, thromboembolic events occurred in 187 (7.4%) and major adverse cardiovascular events in 254 (10.0%). Restricted cubic spline models showed significant nonlinear associations with thromboembolic events (overall P<0.001; nonlinear P=0.007) and major adverse cardiovascular events (overall P<0.001; nonlinear P=0.040). High AIP was independently associated with an increased risk of thromboembolic events after adjustment for conventional comorbidities (model 1: adjusted hazard ratio [aHR], 1.47 [95% CI, 1.07-2.02]), with the association remaining significant after further adjustment for commonly prescribed concomitant treatments (model 2: aHR, 1.38 [95% CI, 1.01-1.88]). Similar results were observed for major adverse cardiovascular events (model 1: aHR, 1.40 [95% CI, 1.07-1.84]; model 2: aHR, 1.35 [95% CI, 1.03-1.76]). No significant associations were found for mortality outcomes.

Conclusions: Elevated AIP identifies anticoagulated patients with AF at increased residual thromboembolic and cardiovascular risk.

Background: Blood-based biomarkers for stroke subtyping could improve triage in emergency settings. We used cross-platform proteomics to identify plasma biomarkers differentiating major stroke diagnostic groups.

Methods: We conducted a case-control study using 2 biorepositories. Plasma was collected in the emergency department from adults with suspected stroke before therapeutic intervention. Differentially enriched proteins were identified across acute ischemic stroke, intracerebral hemorrhage, transient ischemic attack, and stroke mimics using SomaScan discovery proteomics (Grady). Differentially enriched proteins were nominated using pairwise and multigroup comparisons and adjusted for clinical covariates. Protein panels were created using least absolute shrinkage and selection operator logistic regression. Internal validation used repeated nested cross-validation (rCV) and targeted mass spectrometry (MS), while external validation used data-independent acquisition  mass spectrometry in an independent cohort (Yale).

Results: We included 100 subjects (40 with acute ischemic stroke, 20 with intracerebral hemorrhage, 20 with transient ischemic attack, 20 with stroke mimics) in discovery and 80 subjects (20 per group) in external validation cohorts. SomaScan quantified 7307 proteins, of which 61 differentiated stroke subtypes. We identified 7 protein classifiers for acute ischemic stroke (rCV-area under the curve, 0.82 [95% CI, 0.78-0.86]), 6 for intracerebral hemorrhage (rCV-area under the curve, 0.70 [95% CI, 0.64-0.76]), 8 for transient ischemic attack (rCV-area under the curve, 0.78 [95% CI, 0.73-0.84]), and 7 for stroke mimics (rCV-area under the curve, 0.81 [95% CI, 0.77-0.86]). Targeted proteomics internally validated 11 proteins, and data-independent acquisition-mass spectrometry externally validated 32 proteins, including VTN (vitronectin), PLG (plasminogen), and S100A9 as top stroke mimics, transient ischemic attack, and intracerebral hemorrhage classifiers.

Conclusions: This study highlights plasma proteomics as a valuable tool for discovering protein biomarkers of stroke diagnosis. These findings support further validation in larger, multicenter cohorts to facilitate biomarker-guided stroke diagnosis in acute care.

Background: Perivascular adipose tissue (PVAT) attenuation interacts with local and systemic vascular inflammation and consequently contributes to unfavorable clinical outcomes in patients with various cardiovascular diseases.

Methods: We retrospectively analyzed consecutive patients with severe aortic stenosis to investigate the association between PVAT attenuation measured before transcatheter aortic valve replacement (TAVR) and subsequent clinical outcomes. PVAT attenuation was measured using computed tomography angiography images around the aortic valve. The primary outcome was defined as major adverse cardiovascular events (MACE), a composite of all-cause death, stroke, and heart failure rehospitalization.

Results: MACE was observed in 23.6% of 233 patients during a median follow-up of 2.2 years. The MACE group had significantly higher PVAT attenuation than the non-MACE group (-74.0±9.8 Hounsfield unit [HU] versus -78.9±9.2 HU, P=0.001). In the Cox regression model, higher PVAT attenuation was independently associated with MACE (hazard ratio: 1.52 [95% CI: 1.13-2.04], P=0.006). Incorporating PVAT attenuation into established prognostic factors following TAVR improved the predictive and reclassification performance of MACE risk.

Conclusions: Elevated PVAT attenuation around the aortic valve was associated with MACE in patients undergoing TAVR. Measuring PVAT attenuation before TAVR can help identify patients at higher risk of developing heart failure or cardiovascular death after TAVR, thereby aiding in treatment strategy decisions.

Registration: URL: https://www.umin.ac.jp/ctr/; Unique Identifier: UMIN000057107.

Background: Atherosclerotic cardiovascular disease (ASCVD) poses a significant health challenge worldwide. While statins effectively reduce low-density lipoprotein (LDL) cholesterol and lower cardiovascular risk, patients with coronary artery disease who undergo revascularization remain vulnerable to recurrent ASCVD events. This study examined the link between statin intensity, LDL cholesterol levels, and recurrent ASCVD events in patients undergoing coronary interventions within a large health care system.

Methods: We conducted a retrospective analysis using the University of Pittsburgh Medical Center database, including patients aged ≥18 with coronary artery disease confirmed by revascularization (coronary artery bypass graft or percutaneous coronary intervention) since January 2010. Patients were categorized by statin intensity: guideline-directed statin intensity (GDSI), less than GDSI (

Results: Of 45 949 patients (69% men), 65% were on GDSI, 25% on P<0.001 for all). LDL cholesterol levels ≤70 mg/dL correlated with fewer adverse events, multivariable analysis indicated that GDSI significantly lowered recurrent ASCVD events and mortality.

Conclusions: GDSI reduces recurrent ASCVD events and mortality more effectively than less intensive regimens or no statins. Optimizing statin use and LDL cholesterol monitoring could improve ASCVD management and outcomes.

Background: Early rhythm control has been proposed to improve outcomes in patients with atrial fibrillation (AF), but data on its effectiveness in real-world cohorts remain limited. We aimed to evaluate the effectiveness of rhythm control in patients with recently diagnosed AF.

Methods: We included patients with recently diagnosed AF enrolled in the GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) registry phase III. We analyzed rhythm control at baseline, defined as treatment with an antiarrhythmic drug, or having received AF ablation or cardioversion; patients who did not receive any of these treatments were assigned to the "no rhythm control" group. We analyzed factors associated with rhythm control, treatment with an oral anticoagulant, and risk of major outcomes using multivariable regression analyses. The primary outcome for this analysis was the composite of all-cause death and major adverse cardiovascular events.

Results: Of 21 051 patients with AF included in this analysis (mean age, 70.2±10.3 years, 45% women), 6932 (32.9%) received rhythm control. Older age, more sustained forms of AF, and history of thromboembolism were associated with no rhythm control at baseline; conversely, oral anticoagulants were more likely used in patients receiving rhythm control (odds ratio, 1.36 [95% CI, 1.25-1.48]). During 3-year follow-up, rhythm control was associated with lower hazard of the primary composite outcome (hazard ratio, 0.88 [95% CI, 0.80-0.96]). Similar results were observed for other secondary outcomes, including all-cause death, thromboembolism, and major bleeding.

Conclusions: In this real-world cohort of patients with AF, rhythm control was used in 1 of 3 patients, and was associated with higher use of oral anticoagulants and better outcomes.