New Research Explores Benefits of Finerenone in Patients With HFmrEF or HFpEF; More

In patients with heart failure (HF) and mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), finerenone had a significantly lower rate of worsening HF events and cardiovascular-related death than placebo, based on findings from the FINEARTS-HF trial presented at ESC Congress 2024 and simultaneously published in The New England Journal of Medicine.

Stop-or-Not: Continuation vs. Discontinuation of RASIs Before Major Noncardiac Surgery

A continuation strategy of renin-angiotensin system inhibitors (RASIs) before major noncardiac surgery was associated with better postoperative outcomes than discontinuation, based on results from the Stop-or-Not trial presented at ESC Congress 2024 and simultaneously published in JAMA.

ABYSS: Interrupt or Continue Beta-Blocker Treatment in Patients With History of MI?

Interruption of beta-blocker treatment in patients with a history of myocardial infarction (MI) did not reduce risk of cardiovascular events or death, nor did it appear to improve quality of life compared with continuing treatment, based on findings from the ABYSS trial presented at ESC Congress 2024 and simultaneously published in The New England Journal of Medicine.

EPIC-CAD: Edoxaban vs. Dual Antithrombotic Therapy in High-Risk AFib

In patients with high-risk atrial fibrillation (AFib) and stable coronary artery disease, edoxaban monotherapy when given as a long-term antithrombotic therapy was associated with better net clinical benefit than edoxaban plus a single antiplatelet agent, based on findings from the EPIC-CAD trial presented at ESC Congress 2024 and simultaneously published in The New England Journal of Medicine.

CAST-HF: Cardiac Shockwave Therapy For Improving Myocardial Function?

Direct epicardial shockwave therapy administered during CABG in patients with ischemic heart failure (HF) was associated with improvements in left ventricular ejection fraction (LVEF), according to the results of the CAST-HF study published in the European Heart Journal.

Bending Your Mind With Magic? But Wait – The Science is Real!

Shockwave therapy as a novel therapeutic approach in ischemic cardiomyopathy was the focus of the recently reported CAST-HF trial, summarized above. The single-blind, parallel-group, sham-controlled trial randomized patients with left ventricular ejection fraction (LVEF) <40% undergoing CABG to intraoperative myocardial low-intensity shockwave therapy or to a sham procedure after their coronary bypasses were completed.

Follow-up at six months and one year showed significant improvement of LVEF in the shockwave group compared with the sham group, and patient-centered secondary outcomes (six-minute walk and quality of life tests) were all better in the treated group.

Criticism of the trial is easy. The study was small (recruitment stopped early by its ethics committee for benefit) and not all patients had follow-up scans. Patients enrolled early in CAST-HF were randomized at the onset of surgery which could have affected surgical CABG strategy and subsequent clinical outcomes. But the majority of patients enrolled later were not randomized until all bypasses were complete. Follow-up was a relatively short one year.

Nonetheless, results are results. What can be going on? Is this some weird magic? Or is shockwave therapy the holy grail that causes myocardial cell regeneration and therefore improves LVEF? Probably not on both counts.

There is more to the story. At the European Association for Cardio-Thoracic Surgery meeting last October, the authors presented a paper titled "Mechanistic Insights from the CAST-HF Trial," in which they reported the results of 30 CAST-HF patients who had myocardial biopsies taken at the time of their surgery. Transcriptomic analysis of the intraoperative biopsies showed that biglycan (a leucine-rich pro-inflammatory proteoglycan associated with angiogenesis pathways) was highly expressed in the post-shockwave samples but not in sham controls. Both in vitro and in vivo studies confirmed this finding: biglycan is released after shock-wave therapy in cultured endothelial cells and biglycan-knockout animals do not show a positive response to shockwave after left anterior descending ligation.

That's the kind of scientific information that can dispel the magic and contribute to the understanding of what may be going on. Consider this: direct myocardial shockwave therapy at the time of CABG surgery releases biglycan within the myocardium, which may be myocyte-protective against ischemia, may be locally pro-inflammatory, and modulates angiogenesis. "Hibernating" myocardial cells are responsive to these stimuli in their immediate environment, are "awakened" (especially if there is new microvasculature or improvement in microvascular function), and systolic function improves. It is not exactly like pulling a rabbit out of a hat, but it is certainly a possible physiologic basis for a complex mechanism of how shockwave therapy helps LVEF improve post-CABG surgery.

There is clearly much more to learn. A larger, multicenter study is needed to confirm all the clinical findings in the CAST-HF study. Planning is underway. CAST-HF also showed that shockwave therapy applied directly to the myocardium had no observed ill effects, which is an important bonus. Longer term follow-up will help with other lingering questions. Perhaps even external transthoracic shockwave therapy performed postoperatively also can be effective. Looking farther ahead, might there be a role for transthoracic shockwave therapy for patients with diffuse coronary disease? But for now, confirmation of the CAST-HF findings would add a novel therapy to what happens in the cardiac operating room. Is the rabbit hiding in the magic hat named "shockwave," and can that rabbit really become an adjunct to coronary surgery? Wouldn't that be a nice trick to add to our treatment of patients with ischemic myocardium?

Editorial comment by Peter C. Block, MD, FACC, editor-in-chief of Cardiology.