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Editorial
. 2022 Dec;9(6):3698-3701.
doi: 10.1002/ehf2.14159. Epub 2022 Sep 20.

The PARADISE-MI trial: a new opportunity to improve the left ventricular remodelling in reperfused STEMI

Alessandro Bellis  1 , Ciro Mauro  1 , Emanuele Barbato  2 , Bruno Trimarco  2 , Carmine Morisco  2
Affiliations
Editorial

The PARADISE-MI trial: a new opportunity to improve the left ventricular remodelling in reperfused STEMI

Alessandro Bellis et al. ESC Heart Fail. 2022 Dec.
No abstract available

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Conflict of interest statement

All authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Pathophysiological rationale for the early initiation of sacubitril/valsartan (SAC/VAL) in reperfused STEMI patients. The acute thrombotic occlusion of a principal coronary artery determines the formation of a large area at risk of necrosis in the myocardium leading to LVR. The early re‐canalization of culprit coronary artery by primary percutaneous coronary intervention (pPCI) reduces the myocardial ischaemic injury but induces the micro‐embolization phenomenon and the reperfusion injury. Because the controversial efficacy of therapeutic strategies in the treatment of coronary micro‐embolization and given no proven treatment able to fight inflammation determined by reperfusion, the role of drugs aimed to improve myocardial cell survival and regulate the extracellular matrix (ECM) homoeostasis became pivotal to prevent post‐STEMI LVR. Neprilysin inhibition by sacubitril significantly increases levels of bradykinin, natriuretic peptides, substance P, adrenomedullin, and apelins that may account for activation of several intracellular pro‐survival pathways in the reperfused heart. At the same time, valsartan selectively blocks pro‐apoptotic mechanisms mediated by AT‐1Rs and empowers pro‐survival pathways induced by Ang II, which is increased because neprilysin inhibition, through AT‐2Rs. Furthermore, SAC/VAL has been demonstrated to reduce the fibrosis inside the ischaemic myocardium by decreasing soluble ST‐2. ARBs, angiotensin receptor blockers; ARNI, angiotensin receptor neprilysin inhibitor; AT‐1Rs and AT‐2Rs, angiotensin receptors type 1 and 2; LVR, left ventricular remodelling; MRAs, mineralocorticoid receptor antagonists.
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