ABSTRACT
Introduction The role of balloon aortic valvuloplasty (BAV) amid the era of transcatheter aortic valve replacement (TAVR) remains a topic of debate. We sought to study the safety and feasibility of combined balloon aortic valvuloplasty and percutaneous coronary intervention (BAV-PCI). Methods Between November 2009 and July 2020, all patients undergoing BAV were identified and divided into three groups: combined BAV-PCI (group A), BAV with significant unrevascularised CAD (group B) and BAV without significant CAD (group C). Procedural outcomes, 30-day and one-year mortality were compared. Results A total of 264 patients were studied (n = 84, 93 and 87 patients in group A, B and C, respectively). The STS score was 10.2 ±8, 13.3 ±19 and 8.1 ±7, p = 0.026, in group A, B and C, respectively. VARC-3 adjudicated complications were similar among groups (11%, 13% and 5%, respectively, p = 0.168, respectively). Thirty-day and one-year mortality were 9.8% (n =26) and 32% (n = 86) of the entire cohort. The differences among groups did not reach statistical significance. Using univariate Cox regression analysis, group B were at higher risk of dying compared to group A patients (HR 1.58, 95% CI 1.11 - 2.25, p = 0.010). With multivariate Cox regression analysis, the predictors of mortality were STS score, cardiogenic shock, and mode of presentation and lack of subsequent definitive valve intervention. Conclusion In high-risk patients with aortic valve stenosis, combined BAV-PCI is safe and feasible with comparable outcomes to BAV with and without significant CAD.
ABSTRACT
Myocardial infarction (MI) accelerates immune ageing characterised by lymphopenia, expansion of terminally differentiated CD8+ T-lymphocytes (CD8+ TEMRA) and inflammation. Pre-clinical data showed that TA-65, an oral telomerase activator, reduced immune ageing and inflammation after MI. We conducted a double blinded randomised controlled pilot trial evaluating the use of TA-65 to reduce immune cell ageing in patients following MI. Ninety MI patients aged over 65 years were randomised to either TA-65 (16 mg daily) or placebo for 12 months. Peripheral blood leucocytes were analysed by flow cytometry. The pre-defined primary endpoint was the proportion of CD8+ T-lymphocytes which were CD8+ TEMRA after 12 months. Secondary outcomes included high-sensitivity C-reactive protein (hsCRP) levels. Median age of participants was 71 years. Proportions of CD8+ TEMRA did not differ after 12 months between treatment groups. There was a significant increase in mean total lymphocyte count in the TA-65 group after 12 months (estimated treatment effect: + 285 cells/µl (95% CI: 117-452 cells/ µ l, p < 0.004), driven by significant increases from baseline in CD3+, CD4+, and CD8+ T-lymphocytes, B-lymphocytes and natural killer cells. No increase in lymphocyte populations was seen in the placebo group. At 12 months, hsCRP was 62% lower in the TA-65 group compared to placebo (1.1 vs. 2.9 mg/L). Patients in the TA-65 arm experienced significantly fewer adverse events (130 vs. 185, p = 0.002). TA-65 did not alter CD8+ TEMRA but increased all major lymphocyte subsets and reduced hsCRP in elderly patients with MI after 12 months.
Subject(s)
Myocardial Infarction , Telomerase , Aged , Humans , C-Reactive Protein , Inflammation , T-Lymphocytes , Double-Blind MethodABSTRACT
INTRODUCTION: Anthracyclines are included in chemotherapy regimens to treat several different types of cancer and are extremely effective. However, it is recognised that a significant side effect is cardiotoxicity; anthracyclines can cause irreversible damage to cardiac cells and ultimately impaired cardiac function and heart failure, which may only be evident years after exposure. The PROACT trial will establish the effectiveness of the ACE inhibitor enalapril maleate (enalapril) in preventing cardiotoxicity in patients with breast cancer and non-Hodgkin's lymphoma (NHL) receiving anthracycline-based chemotherapy. METHODS AND ANALYSIS: PROACT is a prospective, randomised, open-label, blinded end-point, superiority trial which will recruit adult patients being treated for breast cancer and NHL at NHS hospitals throughout England. The trial aims to recruit 106 participants, who will be randomised to standard care (high-dose anthracycline-based chemotherapy) plus enalapril (intervention) or standard care alone (control). Patients randomised to the intervention arm will receive enalapril (starting at 2.5 mg two times per day and titrating up to a maximum dose of 10 mg two times per day), commencing treatment at least 2 days prior to starting chemotherapy and finishing 3 weeks after their last anthracycline dose. The primary outcome is the presence or absence of cardiac troponin T release at any time during anthracycline treatment, and 1 month after the last dose of anthracycline. Secondary outcomes will focus on cardiac function measured using echocardiogram assessment, adherence to enalapril and side effects. ETHICS AND DISSEMINATION: A favourable opinion was given following research ethics committee review by West Midlands-Edgbaston REC, Ref: 17/WM/0248. Trial findings will be disseminated through engagement with patients, the oncology and cardiology communities, NHS management and commissioning groups and through peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT03265574.
