Rationale and design of the early valve replacement in severe asymptomatic aortic stenosis trial.

BACKGROUND: Aortic valve replacement in asymptomatic severe aortic stenosis is controversial. The Early valve replacement in severe ASYmptomatic Aortic Stenosis (EASY-AS) trial aims to determine whether early aortic valve replacement improves clinical outcomes, quality of life and cost-effectiveness compared to a guideline recommended strategy of 'watchful waiting'. METHODS: In a pragmatic international, open parallel group randomized controlled trial (NCT04204915), 2844 patients with severe aortic stenosis will be randomized 1:1 to either a strategy of early (surgical or transcatheter) aortic valve replacement or aortic valve replacement only if symptoms or impaired left ventricular function develop, or other cardiac surgery becomes nessessary. Exclusion criteria include other severe valvular disease, planned cardiac surgery, ejection fraction <50%, previous aortic valve replacement or life expectancy <2 years. The primary outcome is a composite of cardiovascular mortality or heart failure hospitalization. The primary analysis will be undertaken when 663 primary events have accrued, providing 90% power to detect a reduction in the primary endpoint from 27.7% to 21.6% (hazard ratio 0.75). Secondary endpoints include disability-free survival, days alive and out of hospital, major adverse cardiovascular events and quality of life. RESULTS: Recruitment commenced in March 2020 and is open in the UK, Australia, New Zealand, and Serbia. Feasibility requirements were met in July 2022, and the main phase opened in October 2022, with additional international centers in set-up. CONCLUSIONS: The EASY-AS trial will establish whether a strategy of early aortic valve replacement in asymptomatic patients with severe aortic stenosis reduces cardiovascular mortality or heart failure hospitalization and improves other important outcomes.

Association between direct transport to a cardiac arrest centre and survival following out-of-hospital cardiac arrest: A propensity-matched Aotearoa New Zealand study.

Background and Objectives: Direct transport to a cardiac arrest centre following out-of-hospital cardiac arrest may be associated with higher survival. However, there is limited evidence available to support this within the New Zealand context. This study used a propensity score-matched cohort to investigate whether direct transport to a cardiac arrest centre improved survival in New Zealand. Methods: A retrospective cohort study was conducted using the Aotearoa New Zealand Paramedic Care Collection (ANZPaCC) database for adults treated for out-of-hospital cardiac arrest of presumed cardiac aetiology between 1 July 2018 to 30 June 2023. Propensity score-matched analysis was used to investigate survival at 30-days post-event according to the receiving hospital being a cardiac arrest centre versus a non-cardiac arrest centre. Results: There were 2,297 OHCA patients included. Propensity matching resulted in 554 matched pairs (n = 1108). Thirty-day survival in propensity score-matched patients transported directly to a cardiac arrest centre (56%) versus a non-cardiac arrest centre (45%) was not significantly different (adjusted Odds Ratio 0.78 95%CI 0.54, 1.13, p = 0.19). Shockable presenting rhythm, bystander CPR, and presence of STEMI were associated with a higher odds of 30 day survival (p < 0.05). Maori or Pacific Peoples ethnicity and older age were associated with lower survival (p < 0.05). Conclusions: This study found no statistically significant difference in outcomes for OHCA patients transferred to a cardiac arrest compared to a non-cardiac arrest centre. However, the odds ratio of 0.78, equivalent to a 22% decrease in 30-day mortality, is consistent with benefit associated with management by a cardiac arrest centre. Further research in larger cohorts with detailed information on known outcome predictors, or large randomised clinical trials are needed.

Associations between psychosocial burden and prognostic biomarkers in patients with chronic coronary syndrome: a STABILITY substudy.

AIM: To investigate associations between psychosocial burden and biomarkers reflecting pathophysiological pathways in patients with chronic coronary syndrome. METHODS: Psychosocial (PS) factors were collected from self-assessed questionnaires and biomarkers representing inflammation (high-sensitivity [hs]-C-reactive protein [CRP], interleukin-6 [IL-6], lipoprotein-associated phospholipase A2 [Lp-PLA2]) and cardiac injury/stress (hs-troponin T [hs-TnT], N-terminal pro-B type natriuretic peptide [NT-proBNP]) were measured in 12,492 patients with chronic coronary syndrome in the STABILITY trial. Associations between level of each psychosocial factor (never-rarely (reference), sometimes, often-always) and biomarkers were evaluated using linear models with adjusted geometric mean ratios (GMR). A score comprising four factors ('feeling down', 'loss of interest', financial stress', 'living alone') that previously demonstrated association with cardiovascular (CV) outcome was created, and categorized into three levels: low, moderate and high PS burden. Associations between PS score and biomarkers were evaluated similarly. RESULTS: Greater PS burden was significantly associated with a gradual increase in inflammatory biomarkers (GMR [95% CI] for moderate vs low PS burden; and high vs low PS burden): hs-CRP (1.09 [1.04-1.14]; 1.12 [1.06-1.17]), IL-6 (1.05 [1.02-1.07]; 1.08 [1.05-1.11]), LpPLA2 (1.01 [1.00 - 1.02]; 1.02 [1.01-1.04]) and cardiac biomarkers hs-TnT (1.03 [1.01-1.06]; 1.06 [1.03-1.09]) and NT-proBNP (1.09 [1.04-1.13]; 1.21 [1.15-1.27]). CONCLUSIONS: In patients with chronic coronary syndrome, greater psychosocial burden was associated with increased levels of inflammatory and cardiac biomarkers. While this observational study does not establish causal nature of these associations, the findings suggest inflammation and cardiac injury/stress as plausible pathways linking psychosocial burden to an elevated CV risk, that needs to be further explored.

We studied the association between psychosocial factors and various circulating protein biomarkers, reflecting different underlying mechanisms of disease, with the hope of shedding light on the link between psychological factors like depression and stress and the risk of cardiovascular events in patients with chronic coronary syndrome. We analysed data from the global large-scale STABILITY trial, which included more than 12,000 patients with chronic coronary syndrome. Participants filled out a questionnaire assessing their level of psychosocial burden, including experiences of depressive symptoms, stress at home, at work and financial stress. Additionally, blood samples were collected in which biomarkers (NTproBNP, high-sensitive Troponin-T, Interleukin-6, CRP and LpPLA2) were analysed. Our findings revealed a significant association between higher psychosocial burden and increased concentrations of biomarkers in patients with chronic coronary syndrome. These biomarkers reflect both inflammatory processes and cardiac damage or dysfunction which could be potential disease mechanisms explaining the increased risk of adverse events in patients with chronic coronary syndrome and high psychosocial burden. Although causal relationships cannot be determined from this study, the findings suggest that inflammation and cardiac stress may play crucial roles in linking psychosocial factors to heightened cardiovascular risk in this patient population. These insights could pave the way for better understanding and managing cardiovascular health in individuals with chronic coronary syndrome, offering hope for more targeted interventions in the future.