Journal of the American Heart Association最新文献

Background: Bio-ADM (bioactive adrenomedullin) is a vasoactive peptide hormone that predicts clinical outcomes in heart failure-the main driver of adverse outcomes in cardiac amyloidosis (CA). This prospective observational study sought to assess the prognostic role of bio-ADM in CA.

Methods: Patients with CA were enrolled from amyloid centers in Germany (observation cohort), Japan, and the United States (combined validation cohort). Bio-ADM was quantified using the sphingotest bio-ADM assay. Associations of bio-ADM with all-cause death and major adverse cardiovascular events over 2 years were assessed using Kaplan-Meier and Cox regression analyses. Likelihood ratio chi-square tests for nested models evaluated whether adding bio-ADM improves validated prognostic staging systems.

Results: In both the German observation cohort (n=86) and the combined validation cohort from Japan and the United States (n=124), elevated bio-ADM (>29 pg/mL) was associated with more frequent all-cause death and major adverse cardiovascular events. Bio-ADM remained independently associated with impaired overall (P<0.001) and major adverse cardiovascular events-free survival (P<0.001) after adjustment for age, sex, and established prognostic biomarkers in the entire cohort. Adding categorized bio-ADM (>29 pg/mL) significantly improved the prognostic accuracy of the National Amyloidosis Centre (C-index 0.674 to 0.787; P=0.002) and MayoATTR (C-index 0.662 to 0.757; P<0.001) staging systems for cardiac transthyretin amyloidosis. Adding bio-ADM to staging systems for cardiac immunoglobulin light chain amyloidosis yielded no significant changes.

Conclusions: Bio-ADM is a promising prognostic biomarker, especially in cardiac transthyretin amyloidosis, where it improved risk stratification when added to established staging systems. Further research is needed to clarify its role as part of staging systems for cardiac immunoglobulin light chain amyloidosis.

Background: In the RHEIA (Randomized Research in Women All Comers With Aortic Stenosis) trial, the incidence of the primary end point of death, stroke, or rehospitalization at 1 year was lower with transcatheter aortic valve implantation (TAVI) than with surgical aortic valve replacement. The objective of this substudy was to compare echocardiographic findings in women with severe aortic stenosis following surgical aortic valve replacement or TAVI.

Methods: At 48 European centers, 443 women underwent randomization 1:1, and 420 were treated as randomized. Echocardiograms were available in 356 patients and were analyzed by a core laboratory.

Results: Rates of or greater moderate paravalvular regurgitation was low (<1%) and similar between groups. At 30 days, TAVI was associated with higher mean transprosthetic gradient and smaller aortic valve area, but the rate of severe patient-prosthesis mismatch (3.0 versus 2.6%; P=1) was low and not different between groups. Valve hemodynamics were stable at 1 year. The rate of residual left ventricular hypertrophy (45.3 versus 28.6%; P=0.004) at 1 year was significantly higher with TAVI, whereas the rate of right ventricular systolic dysfunction (14.5 versus 40.7%; P<0.001) and evolution of cardiac damage stage (improved in 21.8 versus 18.1%; worsened in 16.8 versus 47.0%; P=0.001) were better with TAVI.

Conclusions: Among women with severe aortic stenosis, both TAVI and surgical aortic valve replacement achieve excellent valve hemodynamic results with low and similar rates of moderate or greater paravalvular regurgitation or severe patient-prosthesis mismatch. Surgical aortic valve replacement was associated with lower gradients and more pronounced regression of left ventricular hypertrophy, whereas TAVI was associated with better right ventricular systolic function and evolution of cardiac damage stage.

Registration: URL: https://clinicaltrials.gov/study/NCT04160130; Unique Identifier: NCT04160130.

Background: Ascending aortic dilation is monitored with serial imaging, yet event rates are low, with type A dissections often occurring at nonsurgical sizes. We aimed to characterize ascending aortic growth trajectories in a real-world population to understand their clinical consequences and better inform surveillance strategies.

Methods: We conducted a retrospective, single-center study of adults with ≥2 thoracic computed tomography angiography/magnetic resonance angiography examinations. Midascending diameters from clinical reports were used to analyze real-world surveillance effectiveness. Growth trajectories were clustered using latent profile analysis. Early (first 3 scans; n=1997) and extended (first 5 scans; n=757) latent profile analysis models each yielded 4 classes: Stable, Growth, Dramatic Growth, and Fluctuation (an unstable trajectory attributed to measurement noise).

Results: We studied 3363 adults (median age 62 years; 68% men). Stable class was most common (74% Early; 70 % Extended); Growth and Dramatic Growth classes comprised 23% and 2% respectively. Only 1.1% met guideline growth-based criteria for repair, and this subgroup had smaller baseline diameters (37.0 versus 40.3 mm, P=0.009). At Extended follow-up, 80% of those initially Stable remained Stable. Reclassification into a Growth class was associated with younger age and Marfan syndrome (50.0% versus 3.0%, P=0.006). Acute type A dissection was rare (0.45%) and not clearly linked to any trajectory.

Conclusions: Most patients with a dilated ascending aorta show negligible growth and low complication rates during routine surveillance. Repeated imaging beyond 3 scans may amplify uncertainty without clear improvements in risk stratification, suggesting that imaging surveillance may be safely deescalated for stable patients.

Background: Chronic kidney disease (CKD) leads to premature mortality from cardiovascular events before kidney replacement therapy. Despite recognition of syndromes like cardiorenal anemia and cardiovascular-kidney-metabolic, predictive models for kidney and cardiovascular outcomes remain inadequate. This study aimed to develop a minimally invasive, risk model using circulating small extracellular vesicle-derived miRNAs among patients with CKD.

Methods: A derivation cohort (n=36) underwent microarray-based miRNA profiling, and a least absolute shrinkage and selection operator-penalized Cox proportional hazards model was constructed. Validation was performed using TaqMan quantitative polymerase chain reaction in a cohort of 234 patients with CKD without kidney replacement therapy. The primary outcome was a ≥30% reduction in estimated glomerular filtration rate or progression to kidney replacement therapy. The secondary outcome included all-cause mortality, kidney replacement therapy initiation, and major adverse cardiovascular events.

Results: In the derivation cohort, 36% of patients had hypertensive glomerulosclerosis as the underlying CKD cause, increasing to 48% in the validation cohort. Twenty-three miRNAs were significantly downregulated in advanced CKD, associated with cellular senescence, FOXO (forkhead box, class O) signaling, and cell cycle pathways. From these, 3 miRNAs-hsa-let-7d-5p, hsa-miR-24-3p, and hsa-miR-126-3p-were selected and integrated into the final risk score with cystatin C and urinary protein levels, following optimization in the validation cohort. Lower miRNA levels were linked to cardiovascular comorbidities and cardiorenal anemia syndrome. Over a median follow-up of 39 and 59 months, 108 kidney events and 70 composite outcomes occurred. The model effectively predicted adverse outcomes across CKD causes, further stratifying risk within cardiovascular-kidney-metabolic stage classifications.

Conclusions: Circulating small extracellular vesicle-derived miRNA profiles enable a noninvasive, longitudinally predictive model for adverse kidney and cardiovascular outcomes in CKD. This approach may improve early risk identification and clinical decision-making.

Background: Previous studies have identified a link between cancer and cardiovascular disease; however, the underlying genetic and proteomic mechanisms remain unclear. Therefore, this study aimed to investigate the association between cancer diagnosis and cardiovascular mortality and to explore the potential mechanisms involved.

Methods: A total of 379 944 participants without cardiovascular disease at baseline, including 65 047 individuals with cancer, were recruited from the UK Biobank database. The primary end point was cardiovascular death. Multivariate Cox regression was performed to evaluate the risk of cardiovascular death in populations with and without cancer. Genome-wide association studies, phenome-wide association studies, and proteomic analyses were applied to investigate the underlying genetic and proteomic mechanisms.

Results: Multivariate Cox regression analysis showed an increased risk of cardiovascular death in the group with cancer (hazard ratio, 1.50 [95% CI, 1.40-1.61]) after multivariable adjustment. Proteomic analysis confirmed a strong association between cancer and cardiovascular disease, primarily involving pathways related to complement and coagulation cascades, and various inflammatory processes. In contrast, genome-wide association studies and phenome-wide association studies revealed only a limited number of shared genetic variations between cancer and cardiovascular conditions, such as hypertension and cardiac dysrhythmias.

Conclusions: Cardiovascular risk is increased in patients with cancer and may be related to altered expression of inflammation- and coagulation-related proteins. In clinical practice, it is recommended to emphasize the management of endocrine, kidney, and inflammation-related risk factors in the population with cancer.

Background: The prognostic value of handgrip strength, a simple and reliable indicator of sarcopenia, in older patients with heart failure remains uncertain. This study aimed to investigate the prognostic value of handgrip strength in hospitalized patients aged ≥65 years with heart failure.

Methods: This post hoc analysis used data from FRAGILE-HF (Prevalence and Prognostic Value of Physical and Social Frailty in Geriatric Patients Hospitalized for Heart Failure), a prospective, multicenter cohort study involving patients aged ≥65 years hospitalized for heart failure. Handgrip strength was measured before discharge using a dynamometer, with the higher value from 2 trials recorded. Measurements were standardized by dividing 28 and 18 kg for men and women, respectively, per 2019 Asian Working Group for Sarcopenia criteria. Patients were categorized into tertiles (tertile 1, highest; tertile 2, middle; and tertile 3, lowest). The primary outcome was 2-year all-cause death.

Results: Among 1269 patients (median age, 81 years; 57.1% men), 275 died during follow-up. Kaplan-Meier analysis revealed a stepwise increase in death across the lowest handgrip tertiles, which remained significant after multivariable adjustment (tertile 2 versus tertile 1: hazard ratio [HR], 1.64 [95% CI, 1.14-2.37]; P=0.007; tertile 3 versus tertile 1: HR, 2.03 [95% CI, 1.42-2.90]; P<0.001). The analysis using a linear model showed that the prognostic impact of reduced handgrip strength increased with age.

Conclusions: Lower handgrip strength was independently associated with death in older patients with heart failure, with stronger associations observed in the oldest patients. These findings highlight the additional prognostic value of handgrip strength beyond conventional risk factors.

Registration: URL: center6.umin.ac.jp; Unique Identifier: UMIN000023929.

Background: Intravenous thrombolysis for acute ischemic stroke (AIS) is a proven effective treatment. Whether thrombolysis in patients with AIS with recent direct oral anticoagulant (DOAC) use is safe and efficacious is not well established. We aimed to compare outcomes of patients with AIS and recent DOAC use who received thrombolysis to those otherwise eligible but excluded due to recent DOAC use.

Methods: This study included patients for the GWTG (Get With The Guidelines) registry with a diagnosis of AIS within 4.5 hours from last known normal, on a DOAC, and either (1) received intravenous thrombolysis, or (2) were excluded from thrombolysis with coagulopathy being the only reason for exclusion. We used univariate and adjusted binary logistic regression models with clustering by site to compare the 2 groups' functional status (ambulation on discharge and discharge disposition) and reported rates of safety outcomes in the thrombolysis group.

Results: The study sample included 48 907 patients with AIS using a DOAC; 4702 received thrombolysis and 44 205 did not. In adjusted logistic regression models, patients with recent DOAC use receiving thrombolysis had increased odds of independent ambulation at discharge (odds ratio [OR], 1.35[ 95% CI, 1.21-1.50]) and home discharge (OR, 1.33 [95% CI, 1.22-1.46]). The rate of symptomatic intracranial hemorrhage with intravenous thrombolysis in patients with recent DOAC use was 3.5% (95% CI, 3.0%-4.1%).

Conclusions: In this study, intravenous thrombolysis was associated with improved functional outcomes in patients with recent DOAC use and appeared safe. Given the study limitations, findings require validation by prospective trials.

Climate change poses an escalating threat to cardiovascular and cerebrovascular health in the Global South, where vulnerability is amplified by rapid urbanization, poverty, and weak infrastructure. Air pollution (driven by fossil fuel use, industrial growth, and poor regulation) remains a major contributor to cardiovascular disease and respiratory illness, with regions such as South Asia and Sub-Saharan Africa experiencing the highest burdens. Extreme heat, floods, and natural disasters further compound cardiovascular risks through direct physiological stress and disruption of health care systems. Urban heat islands intensify the impact of rising temperatures, especially in low-income and historically marginalized communities with limited access to cooling. Meanwhile, increasingly severe floods, particularly in South and East Asia, demand improved disaster preparedness and urban planning to reduce exposure and health impacts. Many cities in rapidly urbanizing cities in Africa lack basic sanitation and access to clean water, air, and soil. These could have magnified impacts on populations during climate emergencies. To address these interconnected challenges, a global, equity-centered approach is needed, one that strengthens regulatory frameworks, expands access to clean energy and cooling technologies, and promotes urban resilience. Collaborative efforts in air quality monitoring, disaster risk reduction, and adaptation financing must prioritize the unique needs of the Global South, guided by context-specific, scalable solutions that also incorporate intergenerational and environmental justice considerations.

Background: Self-expanding valves (SEVs) have demonstrated superior hemodynamic performance and comparable clinical outcomes to balloon-expandable valves (BEVs) at 1 year in patients with a small aortic annulus. However, long-term data are limited. This study aimed to evaluate 5-year echocardiographic and clinical outcomes of SEVs versus BEVs in patients with small aortic annulus underwent transcatheter aortic valve replacement.

Methods: We analyzed RESOLVE registry patients who underwent transcatheter aortic valve replacement at Cedars-Sinai between 2015 and 2020. Patients with a small aortic annulus (<430 mm² by computed tomography) were included and followed for up to 5 years. The primary outcome was a composite of all-cause mortality, stroke, or heart failure hospitalization. Secondary outcomes included myocardial infarction, pacemaker implantation, aortic valve reintervention, and structural bioprosthetic valve dysfunction.

Results: Among 1392 transcatheter aortic valve replacement recipients, 423 (78 SEVs, 345 BEVs) met the small annulus criteria. SEVs were associated with lower transvalvular gradients and larger indexed effective orifice area at discharge and 1 year (P<0.001). Moderate-to-severe paravalvular leak was more frequent with SEVs at 30 days (7.7% versus 1.5%, P<0.001), as was permanent pacemaker implantation (17.9% versus 6.1%, P<0.001). At 5 years, the primary outcome did not differ significantly (hazard ratio, 1.21; 95% CI, 0.81-1.82; P<0.33). All-cause mortality, stroke, heart failure hospitalization, structural bioprosthetic valve dysfunction, and reintervention rates were similar between groups.

Conclusion: Although SEVs provide better hemodynamic performance in patients with severe aortic stenosis and small annuli, this advantage did not translate into improved survival or reduced cardiovascular events at 5 years.