Circulation: Heart Failure最新文献

Background: Adverse events after durable left ventricular assist devices (LVADs) pose a challenge to survival. However, there are limited risk stratification approaches. Plasma cell-free DNA (cfDNA) offers potential as a biomarker for assessing end-organ injury and risk stratification.

Methods: The study included a multicenter prospective cohort of patients with heart failure with and without LVAD (cohort 1), a separate cohort of patients with heart failure with paired samples before and after LVAD (cohort 2) implantation, and a comparator group of healthy controls. Nuclear cfDNA (ncfDNA) and mitochondrial cfDNA were quantified by digital droplet polymerase chain reaction. Tissue-specific cfDNA was identified using whole-genome bisulfite sequencing. Differences in cfDNA levels by LVAD use were assessed with the Wilcoxon rank-sum test or the paired t test. Outcomes (hemocompatibility-related adverse event-free survival and infection-free survival) by cfDNA tertiles were compared by log-rank tests.

Results: Cohort 1 had 76 patients with LVAD and 144 without LVAD. Cohort 2 had 40 patients with LVAD with samples before and after LVAD. ncfDNA levels were 4-fold higher (9794 versus 2386 copies/mL; P<0.001), and mtDNA was 1.5-fold higher (134 707 versus 82 054 copies/mL; P=0.01) in cohort 1 compared with healthy controls (n=48). Patients without LVAD had higher ncfDNA levels compared with those with LVAD in cohort 1 (11 423 versus 7912 copies/mL; P=0.019). After LVAD placement in cohort 2, ncfDNA nearly halved (18 980 versus 10 228 copies/mL; P<0.001), with significant reductions in innate immune, vascular endothelium, gastrointestinal, and liver cfDNA levels. The highest pre-LVAD tertile of ncfDNA was associated with worse infection-free (hazard ratio, 2.94 [95% CI, 1.31-6.56]; P=0.006) and hemocompatibility-related adverse event-free (hazard ratio, 3.24 [95% CI, 1.03-10.3]; P=0.034) survival.

Conclusions: LVAD implantation was associated with reductions in systemic and tissue-specific cfDNA levels. cfDNA levels offer promise for improving risk stratification of LVAD candidates for post-LVAD outcomes.

Background: Although disease-specific patient-reported outcomes (PROs) are well accepted as direct and indirect clinical outcomes in various diseases, data on PRO performance in adult congenital heart disease (ACHD) are limited to nondisease-specific metrics. We, therefore, investigated the association between responses to a novel ACHD-specific PRO metric and both clinical variables and gold standard PROs.

Methods: We assessed the association between patient-perceived health status as assessed by the summary score of the Adult Congenital Heart Disease Patient-Reported Outcome Version 1 (ACHD PRO V.1) and hospital admission within the preceding 5 years in the English-speaking subgroup of an international cohort of patients with ACHD enrolled in APPROACH IS-II between February 10, 2019, and December 14, 2022. We also examined the relationship between ACHD PRO V.1 domain scores and domain-relevant clinical variables, the Linear Analog Scale Quality of Life, the Patient Health Questionnaire-8, and the Generalized Anxiety Disorder-7.

Results: The analysis includes 333 patients. Both unadjusted and adjusted models revealed that worse patient-perceived health status was associated with unplanned hospital admission (adjusted β, -5.7 [95% CI, -9.9 to -1.6]; P=0.007). Univariate analysis indicated a strong association between ACHD PRO V.1 domains and relevant clinical variables. A moderate correlation was found between the QOL and anxiety/depression domains and their corresponding gold standard (r=0.467, P<0.001 with the Linear Analog Scale Quality of Life; r=-0.581, P<0.001 with the Patient Health Questionnaire-8; and r=-0.540, P<0.001 with the Generalized Anxiety Disorder-7).

Conclusions: A lower ACHD PRO V.1 summary score is associated with a history of unplanned cardiac admission. In addition, the ACHD PRO V.1 domains show good content validity by comparison with relevant clinical conditions and gold standard PROs. These data support the use of the ACHD PRO V.1 as a direct and surrogate clinical outcome in ACHD.

Background: Dilated cardiomyopathy (DCM) is a common cause of heart failure and is associated with substantial morbidity and mortality. However, data on mortality trends and disparities in DCM mortality in the United States are limited. The objective of this study is to define trends and demographic and regional disparities in DCM-related mortality in the United States.

Methods: Data from the Centers for Disease Control and Prevention Wide-ranging Online Data for epidemiological Research were analyzed from 2004 to 2022 for DCM-related mortality in the US population >15 years. Age-adjusted mortality rates (AAMRs) per 100 000 people and associated annual percent changes were analyzed using Joinpoint regression analysis. Mortality trends were stratified by sex, race and ethnicity, age group, census region, urbanization classification, and state.

Results: Between 2004 and 2022, 138 076 DCM-related deaths were reported in the study population. The AAMR decreased from 4.41 in 2004 to 1.98 in 2019 with an average annual percentage change of -5.09 (95% CI, -5.40 to -4.86), after which it increased slightly to 2.22 in 2021. Men consistently had 2- to 2.5-fold higher AAMR compared with women. Non-Hispanic Black people had the highest AAMR. The highest mortality rate during the study period was seen in the older population (age≥75 years). Regionally, the Midwest and South had the highest AAMR in 2004, which was overtaken by the West US after 2010. Rural-urban areas had similar AAMRs for most years.

Conclusions: DCM-related mortality decreased over the past 2 decades, with a slight increase observed during the COVID-19 pandemic. Despite the decreasing trend, sex and racial disparities persisted, with men and Black people having the highest AAMR, whereas regional disparities changed, with the Midwest and South census regions showing an improvement compared with the West of the United States.

Air pollution is a major global environmental health threat and the leading environmental risk factor contributing to cardiovascular morbidity and mortality. Emerging evidence increasingly implicates air pollution as a critical, modifiable driver in the pathogenesis, progression, and prognosis of heart failure. Air pollution is increasingly recognized as part of the exposome-a complex interplay of environmental, social, and behavioral exposures accumulated across the life course. In this review, we synthesize experimental data demonstrating mechanistic links between air pollution and heart failure, along with growing experimental, clinical, and epidemiological evidence connecting both short- and long-term air pollution exposure with increased risk of heart failure progression across heart failure stages. We further examine how air pollution interacts with other exposomic risk domains-such as the social exposome, built environment, and access to greenery-compounding vulnerability in marginalized and underserved populations. The review will also summarize current approaches to communicate air pollution risk and propose practical strategies for both individuals and healthcare systems to mitigate its cardiovascular impact. Finally, we present a clinical framework for assessing and managing air pollution exposure in patients with heart failure, emphasizing the need for targeted risk stratification and the development of context-specific mitigation interventions.

Background: Studies have demonstrated that patients with myocarditis may have a higher burden of cardiomyopathy-associated genetic variants than the general population. However, data on children are limited. We compared the prevalence of rare predicted-damaging variants and clinically pathogenic variants in children with dilated cardiomyopathy (DCM) secondary to myocarditis with that in children with DCM alone and in heart-healthy controls.

Methods: Children with DCM secondary to myocarditis and children with DCM alone who underwent exome sequencing as part of a prior cross-sectional study were identified in the Pediatric Cardiomyopathy Registry, a large multicenter registry of children with cardiomyopathy. Controls from the Indiana University Biobank were matched 4:1 with myocarditis cases on genomic similarity. Rare predicted-damaging variants in cardiomyopathy-associated genes were identified using a bioinformatics approach. Clinical guidelines were used to determine clinical pathogenicity. The prevalence of variants was compared across the 3 groups.

Results: There were 32 patients with DCM secondary to myocarditis. The prevalence of rare predicted-damaging variants was 34.4% (11/32 [95% CI, 18.6%-53.2%]) in cases compared with 6.3% (8/128 [95% CI, 2.7%-11.9%]) in controls (P<0.001). Clinical review indicated all rare predicted-damaging variants in cases were pathogenic (1/12), likely pathogenic (3/12), or variants of uncertain significance (8/12), whereas most variants in controls were benign (2/8) or likely benign (4/8). The prevalence of pathogenic/likely pathogenic variants in cases was 12.5% (95% CI, 3.5%-29.0%) compared with 0% (95% CI, 0%-2.3%) in controls (P<0.01). Rare predicted-damaging and clinically pathogenic/likely pathogenic variant prevalence was not significantly different in children with DCM secondary to myocarditis and DCM without myocarditis (P=0.17 and P=1.00, respectively).

Conclusions: Children with DCM secondary to myocarditis had a higher burden of variants in cardiomyopathy-associated genes than that of heart-healthy controls. Larger studies will be needed to determine the utility of routine genetic testing in this population.