Patients diagnosed with heart failure with reduced ejection fraction (HFrEF) are at increased risk of monomorphic ventricular tachycardia (VT) and ventricular fibrillation. The presence of myocardial fibrosis provides both anatomical and functional barriers that promote arrhythmias in these patients. Propagation of VT in a reentrant circuit depends on the presence of excitable myocardium and the refractoriness of the circuit. We hypothesize that myocardial refractoriness can be modulated surgically in a model of HFrEF, leading to decreased susceptibility to VT.
Male Sprague-Dawley rats were infarcted via permanent left coronary artery ligation. At 3 weeks post-infarction, engineered grafts composed of human dermal fibroblasts cultured into a polyglactin-910 biomaterial were implanted onto the epicardium to cover the area of infarction. Three weeks post-graft treatment, all rats underwent a terminal electrophysiologic study to compare monophasic action potential electroanatomic maps and susceptibility to inducible monomorphic VT.
HFrEF rats (n=29) demonstrated a longer (p=0.0191) ventricular effective refractory period (ERP) and a greater (p=0.0394) VT inducibility compared with sham (n=7). HFrEF rats treated with the graft (n=12) exhibited no change in capture threshold (p=0.3220), but had a longer ventricular ERP (p=0.0029) compared with HFrEF. No statistically significant change in VT incidence was found between HFrEF rats treated with the graft and untreated HFrEF rats (p=0.0834).
Surgical deployment of a fibroblast-containing biomaterial in a rodent ischemic cardiomyopathy model prolonged ventricular ERP as measured by programmed electrical stimulation. This hypothesis-generating study warrants additional studies to further characterize the antiarrhythmic or proarrhythmic effects of this novel surgical therapy.
- heart failure
- cardiac arrhythmias
Statistics from Altmetric.com
Contributors IRC—electrophysiology investigator, performed data acquisition and analyses. MH—clinical cardiac electrophysiologist, assisted in data interpretation. TM—clinical cardiac electrophysiologist, assisted in data interpretation. JWK—biomedical engineer, assisted in creation of biomaterial. EJ—heart failure cardiologist, assisted with rodent model and echocardiography. SG—senior physician scientist, provided scientific guidance. JJL—research scientist, provided biomaterial and scientific guidance.
Funding This work was supported by the NHLBI T32 HL007249-43, WARMER Research Foundation, Sarver Heart Center, and the University of Arizona.
Competing interests JWK, SG, and JJL have disclosed a financial interest in Avery Therapeutics, Inc. to the University of Arizona. In addition, the University of Arizona has a financial interest in Avery Therapeutics, Inc. These interests have been reviewed and are being managed by the University of Arizona in accordance with its policies on outside interests. All other authors have no relevant conflicts to disclose.
Patient consent for publication Not required.
Provenance and peer review Commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as online supplemental information.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.