Circulation: Heart Failure最新文献

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.

Background: People with HIV (PWH) may have a higher risk of heart failure (HF) due to traditional and HIV-related factors. Incidence and risk prediction of HF in PWH are not well characterized. We aimed to quantify the risk of HF events in a global population of PWH with low-to-moderate estimated atherosclerotic cardiovascular disease risk.

Methods: HF incidence (events/1000 person years) was described overall and by demographic, HIV-specific, and HF factors, including estimated Predicting Risk of Cardiovascular Disease Events 10-year risk of HF. Confirmed HF events included adjudicated HF hospitalization and adverse events identified via a standardized Medical Dictionary for Regulatory Archives HF query.

Results: We analyzed 7769 REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) participants from 5 global regions (median, 50 years; 31% female). Over a median follow-up of 5.6 years (interquartile range, 4.3-5.9), HF incidence was higher in women, among Black participants in high-income regions, participants in sub-Saharan Africa, and among those with preexisting hypertension and obesity compared with the absence of these factors. Current and nadir CD4+T-cell count, and HIV-1 RNA level were not related to the incidence of HF events. Median (Q1-Q3) Predicting Risk of Cardiovascular Disease Events HF score was 1.66% (1.01-2.62). HF incidence was 1.65/1000 person-years (95% CI, 1.30-2.09). Expected number of HF events by Predicting Risk of Cardiovascular Disease Events HF (n=73) was consistent with observed (n=67).

Conclusions: Select demographics, clinical factors, and global regions contribute to a higher incidence of HF events among PWH. In PWH, the observed overall number of HF events aligned with the estimated Predicting Risk of Cardiovascular Disease Events HF risk rates.

Background: Decompensated heart failure with reduced ejection fraction (HFrEF) is associated with systemic inflammation that predicts unfavorable outcomes. We aimed to determine whether anakinra, an IL-1 (interleukin-1) blocker, favors inflammation resolution (CRP [C-reactive protein]) and improves peak oxygen consumption (VO₂) in patients with recently decompensated HFrEF.

Methods: We randomized 102 adult patients recently hospitalized for HFrEF and CRP ≥2 mg/L (2:1) to receive anakinra 100 mg subcutaneously daily (n=68) or placebo for 24 weeks (n=34). The primary end point was the peak VO₂ change at 24 weeks. Data are presented as median (Q1, Q3) or number (%).

Results: Of the 102 patients, 84 had primary end point data available (57 treated with anakinra and 27 with placebo). Peak VO₂ increased from 13.0 (10.9, 17.0) to 14.9 (12.0, 18.0) mL·kg⁻¹·min⁻¹ (P<0.001) in the entire cohort, without significant differences between anakinra and placebo (+1.5 [-0.2, +3.4] and +1.2 [+0.5, +3.9] mL·kg⁻¹·min⁻¹, respectively; P=0.40; median difference +0.30 mL·kg⁻¹·min⁻¹ [95% CI from -1.70 to +0.90]). A significant reduction in CRP levels was seen, with a -76% (-87%, -36%) in anakinra-treated patients and -48% (-77%, +14%) in the placebo group (P=0.050 between groups). There were no unexpected treatment-related serious adverse events, and no differences in HFrEF events between groups. CRP<2 mg/L was achieved in 47% and 37% of the anakinra and placebo groups, respectively (P=0.48). Patients achieving CRP<2 mg/L had a significantly greater increase in peak VO₂ versus those with CRP≥2 mg/L (+2.6 [+0.7, +4.6] and +1.0 [-0.3, +1.9] mL·kg⁻¹·min⁻¹; P=0.007) and lower rates of HFrEF-related events (8% and 26%; P=0.045).

Conclusions: Patients with recently decompensated HFrEF treated with maximally tolerated medical therapy had a significant improvement in CRP and peak VO₂. The addition of anakinra had a modest effect on CRP levels and no significant effect on peak VO₂ or other clinically relevant secondary end points.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03797001.

Background: Takotsubo cardiomyopathy is an acute cardiac emergency presenting with severe left ventricular dysfunction. Physical exercise training or cognitive behavioral therapy may enhance myocardial recovery after takotsubo cardiomyopathy.

Methods: In a prospective multicenter clinical trial conducted between February 2020 and August 2023, patients with acute takotsubo cardiomyopathy were randomized 1:1:1 to physical exercise training, cognitive behavioral therapy, or standard care for 12 weeks after index presentation. The primary end point was resting phosphocreatine/gamma-ATP ratio assessed by ³¹P-magnetic resonance spectroscopy. Secondary end points were the rate of oxygen consumption at peak exercise on cardiopulmonary exercise testing, 6-minute walk distance, left ventricular global longitudinal strain, and the Minnesota Living With Heart Failure Questionnaire. Twelve-week changes in outcome were compared between allocated trial interventions.

Results: Seventy-six participants were recruited: the median age was 66 years, and 91% were women. Compared with standard care, the primary end point of myocardial phosphocreatine/gamma-ATP ratio was improved by physical exercise training (0.4 [95% CI, 0.1-0.8]; P=0.016) and cognitive behavioral therapy (0.3 [0.01-0.7]; P=0.043). Both physical exercise training and cognitive behavioral therapy improved rate of oxygen consumption at peak exercise (4.7 [1.4-8.0] and 4.0 [1.5-6.4] mL/min per kg; P=0.001 and 0.004, respectively) and 6-minute walk distance (92.6 [24.7-160.6] and 73.3 [7.9-138.8] m; P=0.004 and 0.029, respectively) compared with standard care. There were no differences in global longitudinal strain or symptom burden.

Conclusions: In patients with acute takotsubo cardiomyopathy, a 12-week intervention with exercise training or cognitive behavioral therapy improved left ventricular myocardial energetics and exercise performance without demonstrable effects on symptoms of heart failure.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04425785.

Background: Patients with cardiovascular conditions like heart failure (HF) often exhibit significant heterogeneity of the risk of clinical events. In clinical trials, large risk heterogeneity can result in an underestimation of treatment effects derived from Cox proportional hazards models. This occurs due to selection bias when estimating the hazard ratio, stemming from a disproportionate reduction of event-free patients in the control group compared with an effective active group over time, ultimately reducing the statistical power. Therefore, it is important to explore alternative analysis methods for outcome trials that are robust with respect to risk heterogeneity.

Methods: We used clinical data from 2 dapagliflozin HF trials-DAPA-HF (Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction) and DELIVER (Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction) to characterize the extent of risk heterogeneity and nonproportionality of hazards in HF. We then evaluated a candidate method for estimating treatment effects in HF outcome trials, namely the survival proportional odds model, and compared this to traditional Cox regression in a simulation study.

Results: In the dapagliflozin trials, nonproportional hazards were a larger issue in the HFpEF population of the DELIVER trial compared with the more homogeneous heart failure with reduced ejection fraction population of the DAPA-HF trial. In simulations of populations with varying degrees of heterogeneity, the survival proportional odds model was more robust to heterogeneity and demonstrated higher power compared with traditional Cox regression in high heterogeneity populations, while performing similarly or slightly worse in more or less heterogeneous populations. Reanalyses of the dapagliflozin trials confirmed these findings, with the survival proportional odds model providing consistently higher power in the DELIVER trial and similar power in the DAPA-HF trial.

Conclusions: In HF trials, the survival proportional odds model is a viable and more robust alternative for analyzing time to event outcomes, also providing an intuitive interpretation of the treatment effect directly linked to survival probability: improved odds of being event-free in the active group compared with the control group.

Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03036124 and NCT03619213.