Journal of the American Heart Association最新文献

Background: Intracranial atherosclerosis is a major cause of ischemic stroke. Vascular shape affects hemodynamics and plaque development. This study aims to investigate the relationships among M1 shape, hemodynamics, plaque distribution, and stroke occurrence using 4-dimensional flow magnetic resonance imaging in patients with ischemic stroke.

Methods: This cross-sectional study included 100 patients with unilateral ischemic stroke (200 M1 segments). Time-averaged wall shear stress (TAWSS) and oscillatory shear index (OSI) were measured at inner- and outer-wall sides at the most curved points and corresponding straight reference sections. Wall thickness, TAWSS, and OSI were assessed for plaque cross-sections near curved points. For plaques on straight sections, TAWSS and OSI were calculated for the thick- and thin-wall sides. In patients with bilaterally curved-shaped M1, TAWSS and OSI at the most curved cross-sections were compared between stroke and nonstroke sides.

Results: For curved-shaped M1, the inner-wall side showed lower TAWSS and higher OSI than the outer-wall and straight reference sections. Plaque cross-sections near curved points showed greater wall thickness and OSI but lower TAWSS at the inner wall. On straight sections, thick-wall side of plaques showed decreased TAWSS and increased OSI. In patients with bilaterally curved-shaped M1, stroke sides exhibited reduced inner-wall TAWSS and elevated outer-wall OSI than nonstroke sides.

Conclusion: Curved M1 shape is associated with disturbed hemodynamics, favoring plaque formation at the inner wall. Local variations in TAWSS and OSI may contribute to stroke risk. Our findings enhance understanding of intracranial atherosclerosis pathophysiology and highlight the value of quantifying vascular geometry and hemodynamics for individualized stroke risk assessment.

Background: The Fontan operation results in chronic hemodynamic alterations, including central venous hypertension, which may contribute to gut dysbiosis. This study aimed to compare gut microbiota profiles between Fontan patients and age- and sex-matched healthy controls and to examine how catheter-measured hemodynamic and liver-related parameters relate to microbial alterations.

Methods: This cross-sectional study enrolled 23 Fontan patients and 23 matched controls. Fontan patients underwent cardiovascular assessments, and stool samples were collected from all participants. Gut microbiota profiles were analyzed using 16S rRNA gene sequencing.

Results: Compared with controls, Fontan patients exhibited distinct gut dysbiosis, with lower evenness and significant shifts in beta-diversity. Fontan patients had higher relative abundances of inflammation-associated taxa and lower abundances of short-chain fatty acid-producing or commensal genera. Higher catheter-measured pulmonary and Fontan-circuit pressures and greater transpulmonary gradients were associated with lower microbial diversity and depletion of several beneficial taxa. In contrast, better liver status-reflected by higher serum albumin-coincided with more favorable microbial profiles.

Conclusions: Fontan patients show a characteristic pattern of gut microbiota disruption that parallels their hemodynamic and hepatic burden. Treating Fontan-related pressures as continuous variables revealed graded associations among circulatory congestion, liver involvement, and gut dysbiosis, supporting a hemodynamic-gut-liver axis in Fontan physiology. Specific bacteria may serve as potential microbial biomarkers for identifying patients at higher risk and for guiding therapeutic interventions aimed at improving clinical outcomes.

Background: Insulin resistance (IR) and lipoprotein(a), Lp(a), are established contributors to cardiovascular disease (CVD) risk. Whether IR modifies the association between Lp(a) and CVD in primary prevention remains uncertain.

Methods: This prospective cohort study included UK Biobank participants without baseline CVD. IR at enrollment was assessed using the triglyceride-glucose index (TyG). The primary outcome was first major adverse cardiovascular event, defined as peripheral arterial disease, coronary artery disease, myocardial infarction, ischemic stroke, or cardiovascular death. Cox models estimated adjusted hazard ratios (aHRs) with 95% CIs for log-transformed Lp(a) and TyG, adjusting for each other. Lp(a) was categorized as <125 or ≥125 nmol/L; high IR was TyG ≥75th cohort percentile. Participants were stratified into 4 joint Lp(a)/IR groups using low Lp(a)/low IR as reference.

Results: Among 328 031 participants (mean age 56.4 years; 54.7% women), 26 865 CVD events occurred over 14.6 years median follow-up (interquartile range 13.7-15.4). Per 1-SD increase, aHRs were 1.08 (95% CI, 1.06-1.09) for log-Lp(a) and 1.06 (95% CI, 1.04-1.07) for TyG, each adjusted for the other. The P-value for the multiplicative interaction between TyG and Lp(a) was 0.07. Relative to reference, aHRs (95% CI) were 1.15 (1.10-1.20) for ≥125/low IR, 1.09 (1.06-1.12) for <125/high IR, and 1.32 (1.24-1.41) for ≥125/high IR.

Conclusions: Lp(a) and IR each independently contribute to cardiovascular risk, with a combination offering improved risk stratification. This suggests that accounting for IR may enhance the assessment of Lp(a)-associated risk in the context of primary CVD prevention setting.

Background: Carpal tunnel syndrome (CTS) has been recognized as a potential early manifestation of systemic amyloidosis; however, its prognostic implications for cardiovascular and renal outcomes remain unclear.

Methods: Using the TriNetX global federated research network, we conducted a retrospective cohort study of patients with bilateral CTS between January 2006 and December 2024. Among 221 902 eligible individuals, 2099 had concomitant amyloidosis. After 1:1 propensity score matching for demographics, comorbidities, medications, and laboratory variables, 1957 matched pairs were analyzed. Outcomes included major adverse cardiovascular events, 3-point major adverse cardiovascular events, heart failure, arrhythmia, dialysis initiation, and major adverse kidney events. Cox proportional hazards models and Kaplan-Meier analyses were performed.

Results: Compared with patients with CTS and amyloidosis (reference group), those without amyloidosis had significantly lower risks of major adverse cardiovascular events (adjusted hazard ratio [aHR], 0.41 [95% CI, 0.28-0.59]), 3-point major adverse cardiovascular events (aHR, 0.26 [95% CI, 0.19-0.35]), heart failure (aHR, 0.45 [95% CI, 0.30-0.64]), arrhythmia (aHR, 0.50 [95% CI, 0.35-0.69]), dialysis initiation (aHR, 0.51 [95% CI, 0.37-0.95]), and major adverse kidney events (aHR, 0.28 [95% CI, 0.25-0.99]; all P<0.05). Kaplan-Meier curves demonstrated consistently lower event-free survival in the amyloidosis group. Sensitivity analyses across alternative modeling strategies yielded directionally consistent results. The median diagnostic delay from CTS to amyloidosis was 3.3 years (interquartile range, 1.4-5.7) and was shorter in the posttafamidis era.

Conclusions: Systemic amyloidosis is associated with substantially increased cardiovascular and renal risks among patients with CTS, highlighting the importance of heightened clinical vigilance and earlier recognition.

Background: Left bundle branch area pacing (LBBAP) is considered to be an alternative modality to deliver cardiac resynchronization therapy (CRT). However, left bundle branch pacing and left ventricular septal pacing (LVSP) are characterized as left bundle branch area pacing. The long-term effect of only LVSP in patients with a CRT indication is still unknown.

Methods: Consecutive patients who met the CRT indication were retrospectively included. LVSP was determined during the procedure. New York Heart Association functional class, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and echocardiographic and pacing parameters were assessed at implant and follow-up visit.

Results: A total of 40 consecutive patients with successful LVSP were included for analysis with a mean follow-up period of 29.4±16.2 months. The QRS complex in lead V₁ during LVSP featured a QS pattern (52.5%), Qr/qR pattern (30%), or rsR pattern (17.5%). LVSP significantly shortened QRS duration (from baseline 172.5±16.8 to 135.3±19.8 ms, P<0.001) with V₆ R-wave peak time of 96.4±9.6 ms. Left ventricular ejection fraction mproved from 26.7±7.4% at baseline to 38.8±16.1% (P<0.001) and a decrease in the LV end-diastolic diameter (67.9±9.8 versus 59.7±10.4 mm; P<0.001) during the follow-up. Echocardiographic response and superresponse were observed in 52.5% and 22.5% of patients, respectively. New York Heart Association functional class improved from 2.7±0.4 at baseline to 1.9±0.6 (P<0.01) and NT-proBNP concentration decreased significantly (4544±975 versus 2353±1225 pg/mL; P<0.001). No procedure-related complications occurred during the implantation procedure.

Conclusions: LVSP is clinically feasible and safe in patients undergoing CRT. LVSP appears to be an alternative CRT pacing strategy with suboptimal ventricular resynchronization.

Background: Stroke is a sexually dimorphic disease, with different risk factors, incidence, outcomes, and treatment responses in men and women. While sex differences have been documented in preclinical studies, these findings often come from single-site studies with small sample sizes and require validation across diverse research settings.

Methods: We used data from the SPAN (Stroke Preclinical Assessment Network), a randomized, placebo-controlled, blinded, multilaboratory trial, to determine if sex differences in neurological outcomes are present in preclinical stroke models. We analyzed data from 665 stroke animals treated with saline, including young mice, diet-induced obese mice, aging mice, young rats, and spontaneously hypertensive rats. We compared the corner test index and brain morphology between the sexes using linear random effect models and assessed the mortality rate using Cox proportional hazard regression models.

Results: No significant sex differences were found in neurological outcome measured with the corner test on either day 7 or day 30 after stroke, regardless of the mouse or rat stroke model used. Additionally, female and male mice exhibited similar infarct sizes on day 2 magnetic resonance imaging and on brain atrophy measures on day 30 after stroke, indicating a lack of sex differences in brain injury. Similarly, no sex differences were observed in acute or chronic sensorimotor or tissue outcomes in young rats. In 1 subanalysis, sex differences were seen in the spontaneously hypertensive rats cohort. Female rats exhibited a higher corner test index on day 30 than males, indicating more severe sensorimotor injury.

Conclusions: In this multicenter preclinical study, we did not detect sex differences in stroke outcomes in mice, although sex differences in behavioral outcomes were observed in spontaneously hypertensive rats. These findings highlight that sex differences may be model-specific and subtle, emphasizing the need for methodological consistency and thoughtful inclusion of diverse animal models in translational stroke research to better understand if sex-specific responses contribute to stroke outcomes.