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Myocardial viability dictates survival and functional improvement after coronary artery bypass grafting (CABG) in patients with postischemic heart failure. Success of surgical revascularisation is limited by non viable myocardium. Therefore, adjunctive therapies inducing myocardial regeneration, applied at the time of surgery, could improve survival and functional outcome. To gain broad clinical applicability, adjunctive myocardial regenerative therapies have to be efficient, easily applicable and safe.
Various cell lines including autologous myoblasts as well as stem cells induce myocardial regeneration. However, production of cells is complex, carries a significant financial burden and can be accompanied by serious adverse effects. More recently, doubts over the scientific accuracy of several heart stem cell trials have been announced.
Shock wave therapy has been used to treat kidney stones for more than 30 years. If applied at low energy levels, shock waves can regenerate infarcted and chronic ischemic myocardium. Shock waves can be delivered percutaneously or direct epicardially. Cardiac shock wave therapy improves ventricular function, regional myocardial wall motion and clinical symptoms in patients with chronic ischemic myocardium. It induces angiogenesis by up-regulation of angiogenic growth factors as well as vasculogeneesis by recruitment of bone-marrow derived endothelial cells. However, percutaneous cardiac shock wave therapy is limited by appropriate acoustic windows – shock waves can not safely be applied over lung tissue.
Direct epicardial shock wave therapy has been shown in a pilot trial to be safe and feasible in a clinical setting and may therefore develop as an adjunctive therapy to CABG surgery, especially in those patients with large myocardial infarcts or areas of non reversible ischemia.
The CAST Trial for the first time aims to proof the beneficial effects of direct cardiac shockwave therapy adjunctive to CABG surgery in patients with reduced ejection fraction in a prospective randomized-controlled manner.
References:
- Gollmann-Tepeköylü C, et al. Shock Wave Therapy Improves Cardiac Function in a Model of Chronic Ischemic Heart Failure: Evidence for a Mechanism Involving VEGF Signaling and the Extracellular Matrix. J Am Heart Assoc. 2018 Oct 16;7(20):e010025. doi:10.1161/JAHA.118.010025. PubMed PMID: 30371289.
- Tepeköylü C, et al. Shockwaves prevent from heart failure after acute myocardial ischaemia via RNA/protein complexes. J Cell Mol Med. 2017 Apr;21(4):791-801. doi: 10.1111/jcmm.13021. PubMed PMID: 27995765.
- Holfeld J, et al. Toll-like receptor 3 signalling mediates angiogenic response upon shock wave treatment of ischaemic muscle. Cardiovasc Res. 2016 Feb 1;109(2):331-43. doi: 10.1093/cvr/cvv272. PubMed PMID: 26676850.
- Holfeld J, et al. Low energy shock wave therapy induces angiogenesis in acute hind-limb ischemia via VEGF receptor 2 phosphorylation. PLoS One. 2014 Aug 5;9(8):e103982. doi: 10.1371/journal.pone.0103982. PubMed PMID: 25093816.
- Holfeld J, et al. Epicardial shock-wave therapy improves ventricular function in a porcine model of ischaemic heart disease. J Tissue Eng Regen Med.2016 Dec;10(12):1057-1064. doi: 10.1002/term.1890. PubMed PMID: 24841341.