The A-CURE Working Group also aims to explore the potential limitations of applying acute unloading in the clinical setting. One of these limitations may be found in data from Professor Michael Cohen of the University of South Alabama, which suggest that many patients being treated for acute myocardial infarction (MI) come into the clinic with the preconditioning signalling cascades already activated due to the wide use of P2Y12 inhibitors.1,2 Many experimental therapies look to exploit these same signalling cascades for therapeutic purposes. If these signals have already been activated in the patients, then experimental therapy will have a limited effect. Professor Cohen concluded that in all preclinical models of ischaemia/reperfusion, any intervention being investigated for its cardioprotective qualities must be evaluated in the presence of P2Y12 blockade to determine whether the second intervention’s protection is additive to that of currently indicated anti-platelet agents.
Dr Ryan Tedford, Assistant Professor of Medicine at Johns Hopkins School of Medicine, gave a presentation on the use of mechanical support for right-sided and biventricular failure. Even patients with chronic right ventricular (RV) failure respond to reductions in afterload. Clinical data suggest that, despite reducing RV load, left ventricular assist device (LVAD) implantation initially worsens the RV adaptation to load. However, continued LVAD support results both in improved RV afterload and RV adaptation as the load decreases, and the relationship between these two remains constant over time.3 RV mechanical circulatory support can be initiated early or later in the treatment of RV failure. Data comparing the benefits of primary versus delayed support have been mixed. A 2009 study found that early implantation of biventricular devices was associated with better outcomes compared to delayed implantation,4 suggesting that the timely implantation of a primary RV assist device is potentially beneficial. A separate study found that temporary RV mechanical circulatory support is an acceptable way to manage postoperative RV failure5 and that this is preferable to biventricular support.6 In most cases, and in the setting of contemporary LVADs, temporary RV support and optimisation of RV load may be sufficient.
Professor Derek Hausenloy of Duke-National University of Singapore discussed the challenges of reducing infarct size following acute MI. The most promising future interventions to limit MI scar size each require application prior to percutaneous coronary intervention (PCI) in order to maximise their effects. This observation aligns with data surrounding the ability of acute unloading to limit MI scar size. It has been shown that applying the glucagon-like peptide-1 agonist exenatide prior to PCI, metoprolol prior to PCI, or remote ischaemic conditioning prior to or at the time of PCI may each limit MI scar formation.7 Professor Hausenloy concluded that new techniques such as unloading and newer therapeutic targets and strategies should further improve outcomes.