Circulation: Heart Failure最新文献

Background: In October 2018, the US heart transplant (HT) allocation system was revised giving patients with left ventricular assist device (LVAD) intermediate priority status. Few studies have examined the impact of this policy change on outcomes among patients with LVAD. We sought to determine how the allocation change impacted waitlist and posttransplant mortality in patients with LVAD.

Methods: We retrospectively assessed the United Network for Organ Sharing registry for patients with LVAD who were listed for or underwent HT between October 2016 and October 2021. We evaluated waitlist mortality using competing risks analysis and a multivariable Fine-Gray model, and posttransplant mortality using Kaplan-Meier survival analysis and a multivariate proportional hazards model.

Results: We analyzed data from 3835 patients with LVAD listed for HT and 3486 patients with LVAD who underwent HT during the study period. Listing for HT preallocation change was significantly associated with an increased risk of waitlist mortality (Gray P=0.0058) compared with postallocation change. After adjustment for covariates, mortality differences by listing era were attenuated, but LVAD brand was significantly associated with waitlist mortality (HM3 versus HMII; hazard ratio, 0.38 [95% CI, 0.21-0.69]; P=0.002; HVAD versus HMII; hazard ratio, 0.79 [95% CI, 0.48-1.30]; P=0.36; overall P=0.004). In contrast, HT postallocation change was associated with increased posttransplant mortality (log-rank P=0.0172) compared with preallocation change. In a multivariable analysis, the association with posttransplant mortality between transplant eras was attenuated, but ischemic time (hazard ratio, 1.16 [95% CI, 1.07-1.26]; P<0.001) and status at time of HT (Status 1-3 versus 4; hazard ratio, 1.29 [95% CI, 1.04-1.61]; P=0.02) were significantly associated with posttransplant mortality.

Conclusions: Among patients with LVAD, lower waitlist mortality postallocation change was likely driven by improved LVAD technology. Higher posttransplant mortality following the allocation change was largely attributable to longer ischemic times and patient acuity.

Background: Multidisciplinary Shock Teams have improved clinical outcomes for cardiogenic shock, but their implementation costs have not been studied. This study's objective was to compare costs between patients treated with and without a Shock Team and determine if the team's implementation is cost-effective compared with standard of care.

Methods: We examined patients with refractory cardiogenic shock treated with or without a Shock Team at a tertiary academic hospital from 2009 to 2018. Real-world hospital data were used to compare costs and outcomes, including survival at discharge, 1-year survival, and quality-adjusted life years gained at 1 year. Incremental cost-effectiveness ratios were calculated over a 1-year time horizon, with parameter uncertainty evaluated through probabilistic sensitivity analysis using 1000 second-order Monte Carlo simulations.

Results: The study involved 244 patients, with 123 treated by the Shock Team and 121 receiving standard of care. Patients were predominantly male (77.5%), with a mean age of 58 (18-92) years. The Shock Team approach improved survival rates at hospital discharge and 1-year follow-up (61.0% versus 47.9%; P=0.04 and 55.0% versus 40.5%; P=0.03, respectively). The incremental cost-effectiveness ratio for increases in survival probability at discharge for the multidisciplinary Shock Team compared with standard of care was $102 088. The incremental cost-effectiveness ratio for increases in survival probability at 1-year was estimated at $96 152 and at $127 862 per 1 quality-adjusted life year gained. Probabilistic sensitivity analysis estimates showed that the Shock Team was cost-effective in the majority of simulations using a willingness-to-pay threshold of $150 000, while it was also dominant in almost one-third of the simulations.

Conclusions: The Shock Team approach for treating refractory cardiogenic shock may be a cost-effective alternative to traditional standard of care. These findings can help prioritize the implementation of Shock Team initiatives to further improve cardiogenic shock outcomes.

Heart failure (HF) is a syndrome affecting all organ systems. While some organ interactions have been studied intensively in HF (such as the cardiorenal interaction), the endocrine gut has to some degree been overlooked. However, there is growing evidence of direct cardiac effects of several hormones secreted from the gastrointestinal tract. For instance, GLP-1 (glucagon-like peptide-1), an incretin hormone secreted from the distal intestine following food intake, has notable effects on the heart, impacting heart rate and contractility. GLP-1 may even possess cardioprotective abilities, such as inhibition of myocardial ischemia and cardiac remodeling. While other gut hormones have been less studied, there is evidence suggesting cardiostimulatory properties of several hormones. Moreover, it has been reported that patients with HF have altered bioavailability of numerous gastrointestinal hormones, which may have prognostic implications. This might indicate an important role of gut hormones in cardiac physiology and pathology, which may be of particular importance in the failing heart. We present an overview of the current knowledge on gut hormones in HF, focusing on HF with reduced ejection fraction, and discuss how these hormones may be regulators of cardiac function and central hemodynamics. Potential therapeutic perspectives are discussed, and knowledge gaps are highlighted herein.

Background: Pulmonary arterial hypertension (PAH) is a disease of progressive right ventricular (RV) failure with high morbidity and mortality. Our goal is to investigate proteomic features and pathways associated with RV-focused outcomes including mortality, RV dilation, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in PAH.

Methods: Participants in a single-institution cohort with 3 years of follow-up underwent proteomic profiling of their plasma using 7288 aptamers (targeting 6467 unique human proteins). Partial least squares discriminant analysis was performed to assess global protein variation associated with mortality, RV dilation, and NT-proBNP levels. Differentially abundant proteins and enriched pathways associated with outcomes were identified following baseline adjustments. RV vulnerability models estimated associations for individuals with similar afterload following adjustment for pulmonary vascular resistance.

Results: A total of 117 participants with PAH were included. Partial least squares discriminant analysis of the proteome showed clear separation between survivors and nonsurvivors, participants with dilated versus nondilated RVs, and across NT-proBNP levels. Proteins and pathways involving the ECM (extracellular matrix) were upregulated in participants who died during follow-up, those with severe RV dilation, and those with higher levels of NT-proBNP. Pulmonary vascular resistance adjustment reinforced the importance of ECM proteins in the association with RV vulnerability, independent of afterload. These findings were confirmed in independent PAH cohorts with available plasma proteomics and RV tissue gene and protein expression.

Conclusions: Distinct plasma proteomic profiles are associated with mortality, RV dilation, and NT-proBNP in PAH. Proteins and pathways governing tissue remodeling are strongly associated with poor outcomes, may mediate RV vulnerability to right heart failure, and represent promising candidates as biomarkers and potential therapeutic targets.

Background: Finerenone improves outcomes in patients with heart failure and mildly reduced or preserved ejection fraction. It is important to understand the efficacy and safety of finerenone in these patients according to age.

Methods: The aim of this analysis was to evaluate the interaction between age and the efficacy and safety of finerenone in the FINEARTS-HF trial (Finerenone Trial to Investigate Efficacy and Safety Compared to Placebo in Patients With Heart Failure). A total of 6001 patients aged 40 to 97 years were stratified by quartile (Q1-Q4) of baseline age: Q1, 40 to 66 years (n=1581); Q2, 67 to 73 years (n=1587); Q3, 74 to 79 years (n=1421); and Q4, ≥80 years (n=1412). FINEARTS-HF evaluated the impact of age on the efficacy of finerenone with respect to the primary composite outcome of cardiovascular death and total (first and recurrent) heart failure events, including heart failure hospitalization or urgent heart failure event, along with secondary efficacy and safety outcomes.

Results: The incidence of primary outcomes increased with age. Finerenone reduced the risk of the primary outcome consistently across all age categories: rate ratio in Q1, 0.70 (95% CI, 0.53-0.92); Q2, 0.83 (95% CI, 0.64-1.07); Q3, 0.98 (95% CI, 0.76-1.26); and Q4, 0.85 (95% CI, 0.67-1.07); P_interaction=0.27. Similarly, a consistent effect was observed for the components of the primary outcome. The mean increase in Kansas City Cardiomyopathy Questionnaire-total symptom score from baseline to 12 months was greater with finerenone than placebo, with a consistent effect across all age categories: mean placebo-corrected change in Q1, 2.87 (95% CI, 1.09-4.66); Q2, 1.24 (95% CI, -0.59 to 3.07); Q3, 0.94 (-0.98 to 2.86); and Q4, 1.24 (-0.90 to 3.38); P_interaction=0.50. Adverse events were similar across all age categories. The odds of experiencing hypotension, elevated creatinine, or hyperkalemia (increased) or hypokalemia (decreased) related to finerenone did not differ by age.

Conclusions: In the FINEARTS-HF trial, finerenone reduced the primary outcome and components of the primary outcome and improved symptoms across a wide age spectrum. In addition, finerenone was safe and well-tolerated, irrespective of age.

Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT04435626 and EudraCT 2020-000306-29.