Injection of pig heart "scaffold" material shown safe in early trial
For MI survivors with moderate left ventricular (LV) dysfunction, an injectable biomaterial designed to mimic healthy extracellular matrix (ECM) was found to be safe in a phase I study.
Billed as a potential new approach to heart failure, VentriGel is an ECM hydrogel made from decellularized porcine myocardium and delivered by transendocardial injection using a catheter.
No adverse events definitely related to VentriGel were reported among 15 study subjects with LV dysfunction persisting at 60 days to 3 years post-MI and who had received percutaneous coronary intervention, according to Karen Christman, PhD, of the Sanford Consortium for Regenerative Medicine in La Jolla, California, and colleagues in their study published online in JACC: Basic to Translational Science.
Only the first patient treated experienced adverse events -- cardiogenic shock and complete heart block -- possibly related to the treatment. This person had a history of trifascicular block, which was added as an exclusion criterion for subsequent study participants.
In addition, there was one intracardiac thrombus potentially attributable to mapping or biomaterial injection, Christman's group noted.
"This first-in-man study established the safety and feasibility of delivering VentriGel in post-MI patients, thus warranting further evaluation in larger, randomized clinical trials," the authors concluded.
“It is hard to be definitive about the utility of the procedure without an (untreated) control group, but given the preliminary safety outcomes it seems that the a randomized trial would be the next best step in the further evaluation of the technology,” agreed Ajay Kirtane, MD, of Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation in New York City. Kirtane was not involved with the research.
VentriGel represents an "alternative paradigm to cell based regenerative medicine strategies" that have historically mostly focused on stem cell therapy, Christman and colleagues suggested.
"After an MI, there is not only cell death, but also an inflammatory response and upregulation of matrix metalloproteinases that degrade the native cardiac ECM. Following the initial inflammation, the area is replaced by a collagen rich scar," they wrote, noting that the goal of VentriGel is replacing this abnormal microenvironment to cue cardiac repair.
"VentriGel is a relatively weak hydrogel, about two orders of magnitude lower than the stiffness of healthy myocardium and therefore would not be expected to act as a mechanical support. Rather it was designed to be delivered via catheter and upon injection, assemble into an open porous and fibrous scaffold to allow for endogenous cells to repopulate and remodel the matrix," the investigators said.
The gel is administered as a single 5.4-mL dose delivered via multiple sequential injections of 0.3 mL each.
Study participants included 15 people who had PCI for ST-segment elevation MI (STEMI) and were left with LV ejection fractions in the 25-45% range. Most were men; average age was 59.6 years; and almost three-quarters of the cohort had Class II heart failure.
Holter monitoring revealed no significant ventricular arrhythmias after VentriGel injection.
Results of the 6-minute walk test improved at 3 months (+35.6 m, P=0.033) and 6 months (+44.4 m, P=0.007), compared to baseline. The New York Heart Association heart failure classifications also showed significant drops at 1 month, which were maintained through 3 and 6 months. The Minnesota Living With Heart Failure Questionnaire score decreased at 1 month but lost significance at 3 and 6 months.
Improvements in these domains tended to be greater among the half of the cohort who received VentriGel at least 12 months post-MI.
"Post-hoc analysis revealed that improvements in LV remodeling data, viable mass, and BNP levels were mainly observed in patients who had their MI greater than 12 months prior to treatment," Christman's team added.
The authors acknowledged the lack of controls in their small phase I study.
"To the best of our knowledge, this study is the first clinical trial to evaluate an injectable biomaterial delivered via percutaneous transendocardial injections for cardiac repair," they said. "The trial was also the first demonstration of using a decellularized ECM hydrogel in any tissue in patients."
VentriGel and other cell-less regenerative therapies have the advantage of being cheap and easily stored, according to Christman and colleagues. "In the case of VentriGel, the cost of manufacturing is at least two orders of magnitude less than cell therapies and it could therefore be a scalable and potentially cost-effective treatment for heart failure."
The study was supported by Ventrix.
Christman co-founded Ventrix and is also a consultant and board member.
Kirtane disclosed institutional funding to Columbia University and/or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, Philips, and ReCor Medical.
JACC: Basic to Translational Science
Source Reference: Traverse JH, et al "First-in-man study of a cardiac extracellular matrix hydrogel in early and late myocardial infarction patients" JACC Basic Transl Sci 2019.
Read the original article on Medpage Today: Could an Extracellular Matrix Gel Rebuild MI-Damaged Hearts?