A few months ago, we delved into the management of akinetic/dyskinetic regions in patients with ischemic left ventricular dysfunction. Today, the focus shifts to hibernating myocardium, the component with the greatest recovery potential within the context of revascularization surgery.

Surgical revascularization has proven to be the optimal therapeutic option to restore ventricular function and enhance survival in patients with ischemic ventricular dysfunction associated with multivessel disease. Among its refined advancements, reaching high-quality standards, are the selection, care, and use of multiple arterial grafts, preoperative functional-guided revascularization, optimization of myocardial protection and perfusion techniques using minicircuits, among others. Nonetheless, the study presented today introduces a completely disruptive concept—a new approach to the pathology and the application of an adjunctive therapy, shockwave therapy.

For some, such therapies may evoke memories of unsuccessful revascularization techniques based on energy sources, such as LASER use. For those unfamiliar with this phase in the “archaeology of cardiac surgery,” it is worth mentioning that this therapy sought to create sinusoids in the thickness of the left ventricular wall via a LASER-induced lesion, through which intracavitary blood could improve myocardial thickness perfusion. Although the concept was innovative, LASER failed in clinical results and was soon relegated to the anecdotal within the specialty.

Shockwaves have demonstrated regenerative effects in various fields, such as the recovery of tendinopathies, healing disorders, bone fractures, chronic cutaneous ulcers, post-stroke spasticity, and even aesthetic medicine treatments. Thus, based on numerous preclinical studies by the Austrian author group, the application of these shockwaves on the myocardium is described in the study we are analyzing today, being pioneers in human application.

In this study, 63 patients with ischemic left ventricular dysfunction (left ventricular ejection fraction <40%), coronary artery disease candidates for surgical revascularization, and regional wall motion abnormalities were recruited, excluding those with extensive scarring by magnetic resonance imaging. Patients were randomized to receive complete revascularization with concurrent shockwave therapy (33 patients) versus controls who underwent only revascularization with application of a shockwave device but without active treatment (30 cases). Revascularization was performed using extracorporeal circulation, a single aortic clamp, and grafting of all vessels >1.5 mm and stenoses >50% (SYNTAX criteria). Shockwave therapy was applied during cardioplegia and after revascularization, delivering 300 pulses per coronary territory with an intensity of 0.38 mJ/mm² and a frequency of 3 Hz. These parameters were defined in prior preclinical studies.

The study does not present peri-procedural results but focuses on the one-year follow-up comparison. Patients receiving concurrent shockwave therapy showed a greater increase in left ventricular ejection fraction from preoperative baseline (+11.3% vs. +6.3%; p = 0.14), improved functional capacity in the 6-minute walk test (127.5 m vs. 43.6 m; p = 0.28), and an enhancement in the Minnesota Living with Heart Failure quality of life questionnaire (11 points vs. 17.3 points; p = 0.15).

The authors conclude that shockwave application on hibernating myocardium concurrently enhances left ventricular ejection fraction and functional capacity in surgically revascularized patients with ischemic ventricular dysfunction.

COMMENTARY:

This study is both intriguing and attractive, featuring a clinical trial design that proposes, for the first time, a clinical application of shockwaves on the myocardium. This energy source consists of electrohydraulic shockwaves. By applying a high potential difference between two points with high water content, a mechanical wave propagates through the tissue, with a pressure peak variation of 120 MPa and a trough of 10 MPa. According to previous preclinical literature by the Austrian group, the therapy stimulates neoangiogenesis and hibernating cardiomyocytes.

While promising, some procedural details that could have been requested of the authors are missing. They meticulously describe minor follow-up losses and two non-cardiac deaths. However, perioperative details would have been beneficial, particularly considering revascularization quality, the primary confounder of results. Aspects such as graft type and number, incomplete revascularization rates (per SYNTAX criteria), and intraoperative non-functional graft rates remain undeclared. Notably, they excluded the impact of shockwave therapy application duration on extracorporeal circulation, as well as the consequences of transducer contact on the heart surface post-revascularization (potentially causing damage to anastomoses or grafts). Finally, the authors acknowledge that the shockwave protocol was developed in humans through unpublished preclinical experiences, with prior data being exclusively derived from animal experiments. While this approach might reflect an effort to safeguard the concept from espionage or plagiarism, there are established methods to protect intellectual property, such as the publication of results, which could have also addressed some of the ethical aspects of the study.

In conclusion, the CAST-HF study introduces a new concept for addressing hibernating myocardium and a novel form of therapy, based on an energy source and employing new technology. A single study is not sufficient to make broad recommendations on this approach, but it will be interesting to follow the development of this therapy to determine its potential for widespread application. Until then, the only shock we will continue to deliver is defibrillation during weaning from extracorporeal circulation, when necessary.

REFERENCE:

Holfeld J, Nägele F, Pölzl L, Engler C, Graber M, Hirsch J, et al. Cardiac shockwave therapy in addition to coronary bypass surgery improves myocardial function in ischaemic heart failure: the CAST-HF trial. Eur Heart J. 2024 Jun 20:ehae341. doi: 10.1093/eurheartj/ehae341.