Norbert Frey (Universitätsklinikum Schleswig-Holstein, Campus Kiel Klinik für Kardiologie und Angiologie, Kiel, Germany) and others report—in Circulation: Cardiovascular Interventions—that an injectable bioresorbable scaffold (IK-5001; BioLineRx, Bellerophon Therapeutics), which is designed to prevent or reverse adverse left ventricular remodelling, could revolutionise treatment after a large myocardial infarction as they found the scaffold to be well tolerated in patients with a ST-segment elevation myocardial infarction (STEMI). They add that their results have prompted the initiation of a multicentre, randomised, controlled trial to confirm the safety and efficacy of the scaffold.
Frey et al comment that there still is an unmet need to “markedly reduce or eliminate the risk of ventricular remodelling and development of heart failure following an extensive acute myocardial infarction”. However, they state that direct injection of biomaterials (such as fibrin or alginate) into the infarct could act as a “stabiliser to internally constrain the infarcted segment from expanding and thereby limiting left ventricular remodelling”.
IK-5001, the authors explain, is an injectable device that comprises a solution of 1% sodium alginate plus 0.3% calcium gluconate which when injected into the infarct-related coronary artery, selectively enters and permeates the infarcted myocardial tissue. “Then, it reversibly crosslinks into a hydrogel into a calcium-dependent manner in situ, thereby forming a temporary bioresorbable scaffold that functions as an artificial extracellular matrix,” Fey et al write. They add that a swine study has indicated that the scaffold is associated with prevention of left ventricular remodelling and enlargement.
The aim of the present study was to test the feasibility of the intracoronary delivery of IK-5001 into the infarct-related artery of 27 patients who had survived a first moderate-to-large myocardial infarction. The primary endpoints were occurrence of adverse events, symptomatic heart failure, renal failure and stroke-related death, and the secondary endpoints were change in baseline in left ventricular dimensions, change from baseline in regional and global wall motion score, change from baseline in ejection fraction, cardiac rupture, and NP-proBNP.
Frey et al report that Thrombolysis in Myocardial Infarction (TIMI) flow grade and TIMI myocardial perfusion grade were minimally changed after the injection of IK-5001 and that delivery of the device did not appear to produce additional myocardial injury. Furthermore, there were no adverse events related to the scaffold.
At six months after the large myocardial infarction, the patients’ left ventricular end diastolic volume index, left ventricular end systolic volume index, and left ventricular ejection fraction were preserved. Frey et al write: “Analysis of the regional wall motion score of the left ventricular segments supplied by the infarct-related artery showed a mild recovery of the infarcted segments. However, because this was a single-group uncontrolled study, it was not possible to compare these values or change from baseline with a control group.”
According to Frey et al, the results of this study and the results of a preclinical study have prompted them to design and launch “PRESERVATION I” [sponsored by Bellerophon Therapeutics]. They explain that this is an ongoing multicentre, randomised trial that aims to determine the safety and efficacy of the IK-5001 for preventing left ventricular remodelling and congestive heart failure in STEMI patients who have undergone successful percutaneous coronary intervention. They conclude: “The ability to deliver biomaterial into the infarct artery by intracoronary injection could revolutionise patient treatment after myocardial infarction and prevent left ventricular remodelling, mechanical complications, heart failure, and death.”
Study author Jonathan Leor (Cardiac Research Institute, Sheba Medical Center, Tel-Hashomer, Israel) told Cardiovascular News: “This novel approach aims to treat high-risk patients with significant, irreversible damage after myocardial infarction, and at risk for remodelling and heart failure.”