Over the past months, despite the unprecedented COVID-19 epidemic that has changed the course of behavior on a global scale, our team at the Electrophysiology Clinical Research and Innovations (EPCRI) department at the Texas Heart Institute has continued its studies to find new solutions to improve the care and treatment of patients with arrhythmias. Under the extremely difficult circumstances of the pandemic, we have not abandoned our resolve to progress — instead, we continue to search for ways that could result in better outcomes for cardiac patients. We are deeply grateful to all who have provided support and guidance throughout this endeavor.
In this paper, we briefly review our new studies as well as provide a progression update about our ongoing studies in the lab.
Using Carbon Nanotube Fibers to Restore Myocardial Conduction
In this collaborative work with Rice University, we studied the role of carbon nanotube fibers (CNTf) as a restorative solution to impaired myocardial conduction. CNTf is a biocompatible, lightweight material with high strength, durability, electrical conductivity, and thermal conductivity, which makes it a suitable candidate for virtually any application requiring these properties in biomedical engineering and electronics industries.1 This study is funded by the American Heart Association (AHA).
Ventricular tachycardia (VT) most commonly occurs in patients with structural heart disease or acute myocardial infarction, and is a potentially life-threatening ventricular arrhythmia as untreated VT could progress to ventricular fibrillation, which is responsible for 80% of sudden cardiac deaths (SCDs).2 Sudden cardiac death is a major worldwide public health problem — it is estimated that about 50-60% of all cardiovascular deaths are SCDs, accounting for 15-20% of all deaths.3,4 The underlying mechanism for re-entrant arrhythmias is impaired myocardial conduction. For the first time, we showed that flexible, strong, conductive CNTf sewn across the epicardial scar reconstructed native electrical conduction in sheep and small animal models. We also found that CNT fibers maintain conduction for a period of 4 weeks after AV node ablation without causing toxicity, fibrosis, or elevated immune response in rats. This study provided the first evidence that using CNTf could be a potential option in the future to treat the leading cause of SCD by reconstructing the native electrical conduction of the heart.5
Carbon Nanotube Fibers as Flexible Pacemaker Leads
Additionally, we assessed the ability of CNTfs to promote antegrade ventriculoatrial (VA) conduction (Figure 1). Further acute and chronic studies in pig models were carried out to assess the ability of CNTf to promote antegrade VA conduction. In both acute and chronic models, CNT fibers were sutured from the left atrium into the left ventricle. Atrial capture was achieved by ventricular pacing near the CNTf in an acute model only. In the acute study, we found that unipolar cathodal pacing is best suited for promoting antegrade conduction rather than bipolar or unipolar anodal pacing. With sufficient output, a pacing signal may be carried further through the myocardium to help with acute restoration of conduction across scarred myocardium. Pacemakers typically implanted in patients use the leads as a cathode (negative electrode), while they can serve as an anode (positive electrode).6
Chronic studies revealed an inflammatory response on the CNTf sewn into the porcine epicardium, similar to those seen with pacemaker leads. This revealed the need for a functionalized fiber that does not promote encapsulation around the fiber. Further modifications of CNT fibers, such as a bioactive coating, should be applied to prevent insulation-layer formation on the fiber over time in long-term applications. This work was virtually presented as a poster at HRS 2020 Science.7
Safe Access to the Pericardial Space and Avoiding Collateral Injury
Percutaneous epicardial access is increasingly used for the purpose of mapping and ablation of cardiac arrhythmia (especially ventricular arrhythmia), epicardial pacing, and left atrial appendage ligation.8
The pericardium is a double-layered fibroserous sac that surrounds the heart and roots of the great vessels: the most superficial layer is known as the fibrous pericardium, and the inner layer is known as the serous pericardium. The serous pericardium consists of two layers, an outer layer (parietal layer), which is fused with fibrous pericardium, and the inner layer (visceral layer), which is directly attached to the heart.9 Between the visceral and parietal layers of the serous pericardium, there is a narrow space called the pericardial cavity, which is filled with 20-25 cc of fluid. The limited space between the layers increases the risk of damage to the myocardial wall (usually the right ventricle) and/or epicardial vessels during epicardial access for the treatment of cardiac arrhythmias.8
We have developed a modified 21G micropuncture needle that uses real-time bioimpedance to ascertain location of the needle tip during access (Figure 2). Our recent work details use of the needle to safely access the pericardium while avoiding significant injury to organs such as the lungs. This needle not only allows for ascertaining tissue type at the tip of the needle, but can also be used in conjunction with commercial electroanatomical mapping systems such as CARTO 3 (Biosense Webster, Inc., a Johnson & Johnson company) and EnSite (Abbott), with no modifications to the needle design. This could pave the way for fluoroless pericardial dry taps. In our study, the needle was used to access the pericardium in four porcine models, and the needle was visualized in vivo by using an electroanatomical map in two porcine models.10
Machine Learning Algorithm for Ablation Procedures
In a collaboration between the EPCRI lab and the Department of Electrical and Computer Engineering at Rice University, a National Science Foundation (NSF) funded machine learning project is being used to develop an algorithm for EP applications to detect the potential locations that should be ablated to treat different arrhythmias and restore normal sinus rhythm. The prediction of time series has long been studied and remains an important machine learning paradigm.11 Our approach is to develop algorithms using data from multiple channels across the heart, which helps physicians find the arrhythmia triggers faster and with more precision. The goal of this study is to generate an algorithm that will be able to determine the areas needing ablation by interpreting the EP studies during ablation procedures. This could enhance management of arrhythmias by decreasing the procedure time and improving the outcome.
Wireless Multisite Pacemaker for Cardiac Resynchronization Therapy
The EPCRI collaborations with Rice University and UCLA have resulted in the development of wirelessly powered leadless pacing and sensing nodes. Our preliminary studies showed that these miniaturized wirelessly powered pacemakers were capable of simultaneously pacing the atrium and both ventricles using multiple miniature chips in porcine models, and were suitable for epicardial implantation.12
We developed wirelessly powered pacemakers featuring µW-level power consumption and a miniaturized and flexible form factor that is suitable for epicardial implantation (Figure 3). Two pacemakers were implanted and powered at 13.56 MHz and 40.68 MHz industrial, scientific, and medical (ISM) bands, showing the maximum operating distance of 11 cm and 8.5 cm from 1 W transmitting (Tx) coils, respectively. Wirelessly powered pacemakers implanted on the RV and LV of a porcine model successfully demonstrated leadless cardiac resynchronization therapy (CRT).12
This NIH-R01 funded project is aiming at further optimizing the pacing chip design and associated control unit. Our next goal in this ongoing research is to test the ability of CRT by applying multisite pacing with these miniaturized wireless pacemakers. Unlike conventional pacemakers that use two to three leads to detect the arrhythmia and deliver CRT, the miniaturized pacemaker could theoretically be deployed in different areas of the heart to allow sensing from numerous locations, creating spatially and temporally resolved electrophysiological maps. These maps can be helpful in providing data-driven, patient-specific algorithms to optimize CRT.
We are also working to develop an endocardial deployment method in the near future.
Injectable Electrodes to Treat Ventricular Arrhythmias
The EPCRI lab is working with the Cosgriff-Hernandez Lab at the University of Texas at Austin to create an injectable electrode to improve and extend myocardial capture for improved pacing outcomes in CRT, which is only successful in up to two-thirds of patients due in part to poor lead placement. The injectable electrodes are made of a biostable, in situ curing conductive hydrogel that imparts the strength and flexibility required to be deployed in epicardial veins. This preliminary work shows exciting promise with large animal in vivo testing, demonstrating capture of the myocardium with low capture thresholds when injected into the anterior interventricular vein. This new technology has the potential to not only improve CRT, but treatment of ventricular arrhythmias as well. This technology may be able to pace over scar as the gel cures in a vein crossing over the scarred myocardium, shorting the re-entrant circuits that cause ventricular arrhythmias (Figure 4).
Incidence of Inappropriate Pause Detection with Remote Cardiac Monitoring by
Insertable Cardiac Monitor
An increasing number of patients use implantable devices for long-term cardiac monitoring. In this retrospective study, we reviewed records of 242 consecutive patients with the Reveal LINQ insertable cardiac monitor system (Medtronic),13 among whom 84 patients (average age 63.4, female = 38) had at least one report of pause episode. There were 41 true pause episodes, and 43 inappropriate (false-positive) pause detections. The accuracy of the device to detect the true pause was 48%. This study suggests that the specificity of the Reveal LINQ to detect pauses is low, and that findings should be reviewed by an expert before being acted upon. This study was virtually presented as a poster at HRS 2020 Science.14
Disclosures: The authors have no conflicts of interest to report regarding the content herein. Mathews M. John, MEng reports grants from the National Institute of Health, National Science Foundation, and Roderick D. MacDonald Research Fund; he also reports the following pending patents: WO2018175348A1 and WO2018039162A3.
- Wu AS, Chou TW. Carbon nanotube fibers for advanced composites. Materials Today. 2012;15:302-310.
- Deng Y, Naeini PS, Razavi M, Collard CD, Tolpin DA, Anton JM. Anesthetic management in radiofrequency catheter ablation of ventricular tachycardia. Tex Heart Inst J. 2016;43:496-502.
- Adabag AS, Luepker RV, Roger VL, Gersh BJ. Sudden cardiac death: epidemiology and risk factors. Nat Rev Cardiol. 2010;7:216-225.
- Srinivasan NT, Schilling RJ. Sudden cardiac death and arrhythmias. Arrhythm Electrophysiol Rev. 2018;7:111-117.
- McCauley MD, Vitale F, Yan JS, et al. In vivo restoration of myocardial conduction with carbon nanotube fibers. Circ Arrhythm Electrophysiol. 2019;12:e007256.
- Occhetta E, Bortnik M, Marino P. Ventricular capture by anodal pacemaker stimulation. EP Europace. 2006;8:385-387.
- John M, Post A, Yan JS, et al. D-PO01-227: Carbon nanotube fibers as flexible pacemaker leads: electrophysiologic characterization. Poster presentation at HRS 2020 Science. Heart Rhythm. 2020;17(5):S185.
- d’Avila A, Koruth JS, Dukkipati S, Reddy VY. Epicardial access for the treatment of cardiac arrhythmias. EP Europace. 2012;14:ii13-ii18.
- Volpe JK, Makaryus AN. Anatomy, thorax, heart and pericardial cavity. StatPearls. Published April 6, 2019. Available at https://www.ncbi.nlm.nih.gov/books/NBK482452/. Accessed July 6, 2020.
- John M, Post A, Burkland DA, et al. Confirming pericardial access by using impedance measurements from a micropuncture needle. Pacing Clin Electrophysiol. 2020;43:593-601.
- BuHamra S, Smaoui N, Gabr M. The Box-Jenkins analysis and neural networks: prediction and time series modelling. Applied Mathematical Modelling. 2003;27:805-815.
- Lyu H, John M, Burkland D, et al. Synchronized biventricular heart pacing in a closed-chest porcine model based on wirelessly powered leadless pacemakers. Sci Rep. 2020;10:2067.
- Pürerfellner H, Sanders P, Pokushalov E, et al, Reveal LINQ Usability Study Investigators. Miniaturized Reveal LINQ insertable cardiac monitoring system: first-in-human experience. Heart Rhythm. 2015;12:1113-1119.
- Payam Safavi-Naeini, Abdi Rasekh, et al. D-PO05-097: Incidence of inappropriate pause detection with remote cardiac monitoring by insertable cardiac monitor. Poster presentation at HRS 2020 Science. Heart Rhythm. 2020;17(5):S505.