Safety and efficacy of direct Cardiac Shockwave Therapy in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting (the CAST-HF trial): study protocol for a randomized controlled trial

Leo Pölzl, Felix Nägele, Michael Graber, Jakob Hirsch, Daniela Lobenwein, Martina Mitrovic, Agnes Mayr, Markus Theurl, Michael Schreinlechner, Matthias Pamminger, Christian Dorfmüller, Michael Grimm, Can Gollmann-Tepeköylü, Johannes Holfeld, Leo Pölzl, Felix Nägele, Michael Graber, Jakob Hirsch, Daniela Lobenwein, Martina Mitrovic, Agnes Mayr, Markus Theurl, Michael Schreinlechner, Matthias Pamminger, Christian Dorfmüller, Michael Grimm, Can Gollmann-Tepeköylü, Johannes Holfeld

Abstract

Background: Coronary artery diseases (CAD) remains a severe socio-economic burden in the Western world. Coronary obstruction and subsequent myocardial ischemia result in progressive replacement of contractile myocardium with dysfunctional, fibrotic scar tissue. Post-infarctional remodeling is causal for the concomitant decline of left-ventricular function and the fatal syndrome of heart failure. Available neurohumoral treatment strategies aim at the improvement of symptoms. Despite extensive research, therapeutic options for myocardial regeneration, including (stem)-cell therapy, gene therapy, cellular reprogramming or tissue engineering, remain purely experimental. Thus, there is an urgent clinical need for novel treatment options for inducing myocardial regeneration and improving left-ventricular function in ischemic cardiomyopathy. Shockwave Therapy (SWT) is a well-established regenerative tool that is effective for the treatment of chronic tendonitis, long-bone non-union and wound-healing disorders. In preclinical trials, SWT regenerated ischemic myocardium via the induction of angiogenesis and the reduction of fibrotic scar tissue, resulting in improved left-ventricular function.

Methods/design: In this prospective, randomized controlled, single-blind, monocentric study, 80 patients with reduced left-ventricular ejection fraction (LVEF≤ 40%) are subjected to coronary-artery bypass-graft surgery (CABG) surgery and randomized in a 1:1 ratio to receive additional cardiac SWT (intervention group; 40 patients) or CABG surgery with sham treatment (control group; 40 patients). This study aims to evaluate (1) the safety and (2) the efficacy of cardiac SWT as adjunctive treatment during CABG surgery for the regeneration of ischemic myocardium. The primary endpoints of the study represent (1) major cardiac events and (2) changes in left-ventricular function 12 months after treatment. Secondary endpoints include 6-min Walk Test distance, improvement of symptoms and assessment of quality of life.

Discussion: This study aims to investigate the safety and efficacy of cardiac SWT during CABG surgery for myocardial regeneration. The induction of angiogenesis, decrease of fibrotic scar tissue formation and, thus, improvement of left-ventricular function could lead to improved quality of life and prognosis for patients with ischemic heart failure. Thus, it could become the first clinically available treatment strategy for the regeneration of ischemic myocardium alleviating the socio-economic burden of heart failure.

Trial registration: ClinicalTrials.gov, ID: NCT03859466. Registered on 1 March 2019.

Keywords: CABG; Clinical trial; Heart failure; Ischemic heart disease; Shockwave.

Conflict of interest statement

JH, CD and MG are shareholders of Heart Regeneration Technologies GmbH, an Innsbruck Medical University spin-off aiming to promote Cardiac Shockwave Therapy (www.heart-regeneration.com). All other authors have nothing to disclose.

Figures

Fig. 1
Fig. 1
Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Figure
Fig. 2
Fig. 2
Cardiac shockwave applicator

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