乌鸦传媒

As an adjunct to bypass surgery for ischemic cardiomyopathy, a cardiac shockwave therapy aimed at regenerating ischemic myocardium boosted left ventricular ejection fraction (LVEF) and physical function at 1 year in a small sham-controlled trial.

The CAST-HF trial showed that, among candidates for coronary artery bypass grafting (CABG) surgery with an LVEF ≤40%, there were larger improvements in LVEF from baseline to 360 days with shockwave therapy than with CABG surgery alone (+11.3% vs +6.3%, P=0.0146), reported a group led by Johannes Holfeld, MD, of the Medical University of Innsbruck in Austria, in the .

Patients randomized to shockwave therapy also had larger improvements from baseline in the 6-minute walk test (+127.5 m vs +43.6 m, P=0.028). However, they ultimately scored about the same on the Minnesota Living with Heart Failure Questionnaire and had similar New York Heart Association (NYHA) functional classes.

"A significant improvement in LVEF was already evident 6 months after the procedure and remained stable for up to 1 year," the authors noted. "The extent of improvement of LVEF shown in the CAST-HF trial therefore is of clinical relevance and reflected in patient-reported outcomes."

CABG currently has a for ischemic heart failure in the guidelines, as surgical revascularization was associated with a survival benefit in the 10-year STICH extension study.

Before CAST-HF, however, strategies for myocardial regeneration adjunctive to revascularization had not yielded success in improving LVEF.

"Further trials with larger sample sizes in this patient population are therefore warranted to evaluate whether the beneficial effects of direct cardiac SWT [shockwave therapy] on myocardial function translate into better clinical outcomes, as suggested by the current trial," the authors wrote.

Notably, CAST-HF had been stopped early due to a favorable interim analysis performed when 20 patients per arm had attained 1-year follow-up. The trial made it to publication after interim results had been presented at the European Association for Cardio-Thoracic Surgery meeting nearly 2 years ago.

"We had to wait for all analysis to prepare the publication. Then it took quite a long time for the peer-review process as medical journals and their reviewers are very critical upon completely new therapies in order to rule out any fakes," Holfeld explained to 乌鸦传媒.

The investigators said that two patients in the treatment group died from non-device-related causes. No device-related adverse or serious adverse events were reported.

Shockwave therapy is thought to trigger regeneration of soft tissues by pulsing sonic pressure waves through tissues and activating the innate immune system. Evidence has suggested it can help people with tendonitis, non-healing bone fractures, chronic leg ulcers and soft tissue wounds, post-stroke spasticity, and spinal cord injury, Holfeld and colleagues said.

In chronic ischemic heart failure, they explained, this technology theoretically induces angiogenesis in hibernating myocardium for improved cardiac function. CAST-HF tested this concept using a proprietary device coupled with an applicator that has direct contact with the myocardium and sends sonic waves to all areas of the heart.

Surgeons applied this to areas with wall motion abnormalities identified in preoperative MRI, while the patient was still on the table following CABG. In each instance, shockwaves were delivered via a sterile single-use applicator releasing electrohydraulic shockwaves at 300 impulses per coronary supply territory applied, at an energy flux density of 0.38 mJ/mm² and a frequency of 3 Hz.

"Intraoperative application of direct cardiac SWT is technically a straightforward and short procedure that takes <15 minutes and can be performed during the usual reperfusion time after opening the aortic cross-clamp. As a result, neither anesthesia nor operating times are affected by the addition of SWT to CABG surgery," the authors wrote.

Control group patients received a sham treatment with an inactive applicator.

The CAST-HF trial was conducted at a single center and enrolled CABG candidates with an LVEF ≤40%. It took more than 3 years for investigators to find 63 patients to randomize due to the COVID-19 pandemic, Holfeld said.

All participants underwent on-pump, single cross-clamp CABG surgery aiming for complete revascularization of all vessels at least 1.5 mm in diameter with ≥50% stenosis.

Mean age was 64 years, and 11% were women. Seven in 10 had NYHA class III-IV disease, and mean LVEF was 31%. SYNTAX score was intermediate or high in 75% of patients.

NT-proBNP levels did not differ between groups at 1 year. Rates of repeat angiography, re-hospitalization, and survival were also about the same.

There were two deaths in the CABG plus shockwave therapy arm:

• A 56-year-old man with multiple comorbid conditions died after out-of-hospital cardiac arrest 9 months after surgery. Cause of death was identified as an acute myocardial infarction of the anterior wall after an autopsy. CABG grafts had been patent at the time of death.
• A 73-year-old had a sudden cardiac arrest on the 18th day after surgery, which was judged to be related to multiple morbidity (including ischemic mitral regurgitation). No autopsy was performed.

Holfeld's group explained that they selected the surgical route for shockwave therapy in this trial after early experiences found that a percutaneous application would be hindered by lung tissue covering the heart.

Indeed, there is little appetite for percutaneous coronary intervention (PCI) in this setting after the REVIVED trial showed that this approach was unable to provide a clinical benefit to patients with severely reduced LVEF and coronary artery disease with evidence of myocardial viability in various segments.

That was followed by the REVIVED-BCIS2 study in which patients with more extensive myocardial viability still did not have better outcomes after PCI in this setting -- leading researchers to question the concept of hibernating myocardium altogether.

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