A Theoretical Cardiac Resynchronization Therapy Method to Augment Ventricular Contraction Using Polymer-Based Actuators and Mitral Regurgitation Reduction With Devices Over Left Ventricular Endocardial Pacing Wire — An In-Vitro Study

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Abstract: Background. To investigate a potential cardiac resynchronization method using high force density actuators and mitral regurgitation (MR) reduction devices. Methods. An 8-cm long, 0.4-mm thick, and 2-mm wide polymeric actuator strip was attached to the right ventricular (RV) pacemaker lead 4.0 cm from the edge of the leads, and 035 wire and step-up voltages (2-9 V) were given. Deformation of the pacemaker lead with polymer was studied under cine-fluoroscopy in the air and immersing it in 0.9% saline. Cantilever function was assessed by the addition of gold rings. The left ventricular (LV) lead was reinforced with dual polymer and a side branching 035 wire Y-attachment and studied. A novel nitinol-based Gore-Tex device and polymer-based technology was developed and positioned abutting the mitral valves, and was evaluated in sheep heart preparations by cine-fluoroscopy. Results. The mean deformation at 9 V for the LV leads, RV leads, and 035 wires was 3.5 ± 0.2 mm, 1.1 ± 0.1 mm, and 1.4 ± 0.1 mm, respectively, and the stopping weight was 3.8 ± 0.2 g, 3.2 ± 0.1 g, and 3.6 ± 0.3 g, respectively. With dual surfacing of polymer and driven by separate actuation circuits simultaneously, the stopping weight parameters increased to 4.8 ± 0.2 g, 4.0 ± 0.2 g, and 4.6 ± 0.1 g, respectively (>25% each; P<.01 for all). The nitinol-based Gore-Tex device and the polymer device appeared to have reduced MR significantly from grade IV to grade I (>60% by visual quantification). Conclusion. There is potential for a novel theoretical cardiac resynchronization therapy method using polymer-based actuators and devices to control MR.

J INVASIVE CARDIOL 2013;25(8):415-420

Key words: heart failure, ejection fraction, mitral regurgitation, cardiac resynchronization therapy, polymer actuators, new device

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Systolic heart failure is characterized by reduced ejection fraction, and cardiac resynchronization (CRT) is a known therapy for improvement in ejection fraction in patients with intraventricular or interventricular dyssynchrony. CRT also reduces mitral regurgitation (MR), myocardial oxygen consumption, and hospitalization rates, as well as the mortality rate in heart failure patients.^1-3 It is well known to improve the quality of life in patients with heart failure.^1,3 Electroactive polymers have commercial and research applications from macro- and microrobotics in various fields. ^4-7 These polymers can be used for steerable wires and catheters. 

We investigated a novel theoretical CRT method using polymer-based actuators with reduction in MR. In this model, the leads in conventional CRT are reinforced with electroactive polymers of about 4 cm in length from the distal tip. There is an additional lead in this model with MR reduction devices, which functions by mechanically occluding the effective MR orifice. This additional lead is also useful for pacing the left ventricular (LV) apex through endocardium. The MR reduction devices are nitinol-based Gore-Tex with a polymer patch technology apposing the MR orifice. 

 Methods 

We chose 2-mm wide, 0.4-mm thick, 8-cm long strips of high force density, Teflon-based polymer, which were attached to tined 6 Fr right ventricular (RV) lead, 4 Fr spiral-tipped LV lead and to a standard 035 introducer wire by a glue, 4 cm from the edge of the leads. This high force density Teflon polymer is an ionic polymer-metal composite. The experimental set-up is shown in Figures 1 and 2. The high force density Teflon materials and pulse generators were obtained from Environmental Robotics, Inc. These are bending polymers, which bend on supplying electric current (2-9 V) to the polymers.

Through an electrical circuit, serial step-up voltages 2-9 V were given to the polymer strip by alligator electrodes at 5 cm from the tip and pulse widths were also varied serially. To assess the cantilever function of the wire, serial gold rings of incremental weights were attached to the tip and the beam of the polymer-surfaced area of the pacemaker lead and 035 wire, and the stopping weights were measured. 

  An oscilloscope was used to study the output voltages and pulse widths. To maintain uniformity and standardization of the parametric results and to maintain veracity, a standard pulse frequency of 1/s was chosen. The deformation of the leads was studied after freely suspending the lead with polymer strip in the air by cine-fluoroscopy in a cardiac catheterization laboratory (Siemens Axiom Artis). To further augment the method, a 2-mm wide, 0.4-mm thick, and 8-cm long polymer strip was attached to a 035 wire and thereafter deformation and cantilever function were studied. 

 Finally, the LV lead with polymer was reinforced with another strip of polymer with similar dimensions and the deformation parameters and cantilever function were studied. The two strips of polymer were connected proximally to each other by a thin gold wire, which acts as an electrode to facilitate the flow of current between the two polymer strips (Figure 2E). Thereafter, the two surfaces of polymer were connected independently by two separate circuits and were driven simultaneously. The two circuits were synchronized manually with a stopwatch on trial and error basis. The experiment was further studied in normal saline, to mimic a physiologic milieu. 

The circuit used in the study has an in-built ballast. Therefore, the circuit cannot process more voltages than the upper limit of tolerated ballistic voltage. Hence, the circuit did not support more than 9 V by serial connection with two 9 V batteries. For deformation and stopping weight parameters, an average of 3 consecutive readings was taken for analysis. 

A nitinol device prototype that was diamond shaped and had Gore-Tex sutured along the side was built. The Gore-Tex patch was sutured in various shapes over the device after adjusting the tension (Figure 3), and the surface area was calculated mathematically. The spherical form had the maximal surface area. The device was threaded over a 5 Fr screw-in pacemaker lead (St Jude) and firmly fixed over the pacing lead by retention sutures (Figure 4). The device has two antennas in the proximal end, which is meant to suspend the device from the atrial septum to improve stability of the device. The nitinol device prototypes were built by STI Laser Industries, Inc. Similarly, a polymer patch was threaded over a 5 Fr screw-in pacing lead wire, which was fixed to the LV apex (Figures 5 and 6). For better stability, sutures were taken from the edges of the polymer and a neo-valve prototype was built. The reactionary force at the edge of the lead was estimated after suspension of the sheep heart preparation by the lead. Later, the reactionary force at the attachment of the antennas was studied by suspending weights from the antennas.

The polymer was positioned immediately above the mitral valves apposing the mitral valves. The polymer material was chosen from commercially available Candy Fan, Mars due to its favorable stress and strain properties. Fourier transmission infrared spectroscopy, energy dispersive x-ray spectroscopy (EDAX), and scanning electron microscopy of the polymer were performed to analyze its biophysical and chemical characteristics. 

For evaluation, the device was positioned immediately above, abutting the mitral valves after creating MR in a sheep heart preparation after mechanically cutting the chords across the edges of mitral leaflets. Through a pigtail catheter in the left ventricle, contrast injection was given at various pressures (800 and 1200 psi) and the extent of MR jet was studied. An experienced interventional cardiologist quantified the MR jet visually, and the severity was graded form I to IV. Two experiments were performed for each device, and the results were tabulated. Grade IV MR was induced initially by cutting the chords. Thereafter, the device was positioned, and the extent of MR was studied.

Results 

The results are shown in Table 1. The interobserver and intraobserver variability for all the measured parameters was less than 9%. The RV pacemaker lead with polymer at incremental voltages showed incremental deformation from 0.8 mm at 4 V to 1.00 mm at 7 V at pulse frequency of 1/s. However, at 8 and 9 V, there was only a minimal increase in response. The mean deformation at 9 V for the LV leads, RV leads, and 035 wires was 3.5 ± 0.1 mm, 1.1 ± 0.1 mm, and 1.4 ± 0.1 mm, respectively and the stopping weight was 3.8 ± 0.2 g, 3.2 ± 0.1 g, and 3.6 ± 0.3 g, respectively. The leads and wire maintained deformation for more than 1 hour in various states of humidity. The wire retained 0.5 mm minimal deformation with 4.2 g weights on the beam at 6 V.

The LV lead at 4 Fr showed marked deformation. However, the cantilever force was similar to the RV lead (Table 1). Dual surfacing of leads with polymer and driven by a single circuit only minimally increased deformation and cantilever force parameters. However, with dual surfacing of polymer strips and driven by separate actuation circuits simultaneously, the stopping weight parameters increased significantly to 4.8 ± 0.2 g, 4.0 ± 0.2 g, and 4.6 ± 0.1 g, respectively (>25% each; P<.001 for all). In comparison to study in the air, there was a significant reduction in deformation in saline for LV leads (P=.01), RV leads (P=.03), and 035 wire (P=.03). The stopping weight parameters for RV, LV, and 035 attachment wires were 3.8 ± 0.2 g, 4.5 ± 0.3 g, and 4.4 ± 0.2 g, respectively. These stopping weight parameters were not significant in comparison to measurements in the air (P>.05 for each). 

The nitinol-based Gore-Tex device and the polymer patch appeared to be effective in reducing MR by more than 60% by visual quantification. More objectively, in all the experiments performed, both devices appeared to reduce MR from grade IV to grade I. 

Discussion

This study is an endeavor to build a novel theoretical CRT method using electroactive polymers. The experiments demonstrated the theoretical potential of high force density Teflon-based polymers in lead deformation with a nominal cantilever force. The study also outlines the possible potential of LV endocardial pacing lead with devices to control MR.

Based on the observations in this study, we hypothesize a theoretical CRT method (Figure 7) with dual circuits in the pulse generator and dual surfacing of the polymer on the leads at the distal 4 cm from lead edges, as a potential model for the future. Activation of the two-polymer surface of the leads simultaneously by synchronization of circuits using a timer circuit would produce maximal bending and cantilever force at the tip of the leads. A separate pacing lead to pace LV apex through endocardium, which carries the nitinol or polymer device for MR reduction, is included in the hypothesized method. 

The results are preliminary and need to be independently confirmed both in vivo and in vitro.  Additional research and development are necessary to determine whether any beneficial effects exist from the described theoretical model, and whether it could truly enhance the LV ejection fraction and improve MR.

Conclusion

There may be a theoretical potential to augment ventricular contraction using polymer-based actuators and possible MR reduction with devices over endocardial pacing wire. Additional significant research and development are required in order to determine whether the polymer action can actually augment cardiac performance and improve MR, and provide cardiac resynchronization therapy.

Acknowledgment. We would like to thank Dr Yoseph Bar-Cohen, Senior Scientist, Jet Propulsion Laboratory, NASA for his discussion; Mr Abdul Harif for interobserver variability analysis; Dr M. Ramasamy, for scanning electron microscope pictures and EDAX results; and Dr Sivapragasam for quantification of output voltages with oscilloscope.

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