Safety and Feasibility of a Novel Active Fixation Temporary Pacing Lead

Abstract: Objective. This first-in-human study evaluated the safety and technical feasibility of the Tempo temporary cardiac pacing lead (BioTrace Medical), which includes a novel fixation mechanism and soft tip. Background. Complications of temporary pacing leads include dislodgment, arrhythmias, and ventricular perforation. Temporary pacing applications have increased with transcatheter aortic valve replacement (TAVR) growth, for rapid pacing during balloon valvuloplasty (BAV) and valve deployment, and for periprocedural bradyarrhythmia support. Methods. Eligible patients required temporary pacing for TAVR, BAV, or electrophysiology (EP) procedures. Transthoracic echocardiograms were obtained at baseline and 24 hours after lead removal. Safety was defined as freedom from pericardial effusion requiring intervention or evidence of tamponade. Technical feasibility involved successful intracardiac delivery and pace capture. Additional evaluations included pacing threshold (PCT), rapid pacing, dislodgment, or sustained ventricular arrhythmias. Follow-up was to 30 days. Results. Twenty-five patients (60% female; mean age, 64 ± 19 years) underwent 13 TAVRs (7 Sapien 3 valves [Edwards Lifesciences], 4 CoreValves [Medtronic], and 2 Lotus valves [Boston Scientific]), 11 EP procedures, and 1 BAV at two New Zealand centers from January 2016 to June 2016. Safety was met in all patients, with no device-related adverse events. Technical feasibility was achieved in 23 cases (92%); 2 patients had unsuitable anatomy. No patient had lead dislodgment or sustained ventricular arrhythmias, and the final procedural PCT was 0.7 ± 0.5 mA. Rapid pacing was successful in all cases. Five patients had successful postprocedural use up to 5 days. Conclusion. This first-in-human study demonstrates the safety and technical feasibility of the Tempo lead, providing stable periprocedural temporary pacing support.

J INVASIVE CARDIOL 2018;30(5):163-167. Epub 2018 February 15.

Key words: interventional devices/innovation, new devices, structural heart disease intervention, transcatheter valve implantation

Temporary pacing leads are frequently used to support patients with transient bradyarrhythmias, but are associated with serious complications including cardiac perforation (up to 4%), dislodgment (10%-37%) with loss of pace capture, and thromboembolism.^1-6 Temporary pacing leads have gained an increased role as a necessary adjunct to transcatheter aortic valve replacement (TAVR). Moreover, recent clinical studies of patients undergoing TAVR have confirmed the frequent previously documented complications related to temporary pacing.^7-10

Despite the limitations of current leads, technological development of temporary pacing has been minimal for decades. Standard temporary pacing leads have two electrodes mounted on the distal end with one rigid metal electrode at the distal tip. The rigid distal tip predisposes the lead to myocardial perforation. The leads are also unstable due to the lack of a myocardial fixation modality. One exception, the Medtronic temporary transvenous pacing lead (Model 6416), which uses active helix fixation adapted from permanent lead designs, has been associated with a high rate of cardiac perforation.^11,12

Therefore, there is an unmet need for temporary pacing lead technology that can improve on the safety and efficacy of current leads. This first-in-human study evaluated the safety and technical feasibility of the Tempo temporary pacing lead (BioTrace Medical) when used to provide periprocedural pacing support for catheter-based cardiac procedures including TAVR. 

Methods

The Tempo lead (Figure 1) is a radiopaque, polymeric lead featuring active fixation, bipolar electrodes, and a soft tip. The design replaces the standard metallic electrode tip with an atraumatic distal tip to reduce the risk of cardiac perforation. In addition, the Tempo lead contains a handle-actuated fixation mechanism aimed at enhancing myocardial attachment using novel active-fixation loops to maintain stable pace capture. An elastomeric balloon, which is mounted asymmetrically on the lead body between the electrodes, inflates to aid passage of the lead into the right ventricle as well as enhancing wall apposition of the stabilizing loops (Figure 2). The system is designed for temporary transvenous intracardiac pacing for up to 7 days.

Study design. This was a prospective, single-arm, non-randomized study evaluating the safety and technical feasibility of the Tempo lead. Twenty-five subjects who were undergoing a transcatheter cardiac procedure requiring temporary intracardiac pacing were enrolled at two study centers. These procedures included TAVR, balloon aortic valvuloplasty (BAV), and electrophysiology studies with ablation of paroxysmal supraventricular tachycardia and atrial flutter. The subjects underwent a protocol-driven evaluation immediately post procedure and at 24 ± 8 hours post lead removal; safety follow-up was also conducted at 30 ± 7 days.

Safety was defined as freedom from: (1) pericardial effusion requiring intervention; and/or (2) clinical and/or echocardiographic evidence of cardiac tamponade following placement of and attributable to the Tempo lead. Intervention was defined as percutaneous or surgical drainage of pericardial effusion. Technical feasibility was evaluated as the ability of a Tempo lead to access the right ventricle of the heart and achieve pace capture. Additional evaluations included presence and grade of pericardial effusion, as compared with baseline, on transthoracic echocardiogram obtained 24 ± 8 hr after Tempo lead removal, incidence of ≥1 episodes of failure to pace, pacing threshold stability during Tempo lead use, incidence of lead removal or dislodgment, and incidence of sustained ventricular arrhythmias during Tempo lead use lasting >30 seconds.

Inclusion/exclusion criteria. All study subjects required temporary intracardiac pacing for one of the listed study indications. Main exclusion criteria were: previous permanent pacemaker or implantable cardioverter defibrillator with a right ventricular lead; prosthetic tricuspid valve; severe left ventricular systolic dysfunction (ejection fraction ≤25%); cardiogenic shock; severe mitral or tricuspid regurgitation; severe right ventricular enlargement or dilation; severe pulmonary hypertension (mean pulmonary arterial pressure >60 mm Hg and/or right ventricular systolic pressure >80 mm Hg); chronic oral steroid therapy, chronic pulmonary disease with forced expiratory volume during the first second of force breath (FEV1) of <30% predicted or requiring home oxygen; known coagulopathy and/or thrombocytopenia (platelets <100 x 10³/µL); major bleeding within the previous 6 months or a contraindication to anticoagulation; oral anticoagulation or low-molecular-weight heparin (LMWH) within the preceding 48 hours; international normalized ratio (INR) >1.8; unfractionated heparin administration within 8 hr of the procedure; cardiac surgery within the past 2 months; stroke within the past 3 months; chronic kidney disease (CKD) ≥ stage 4; active systemic infection; pregnant or lactating; and >mild pericardial effusion immediately prior to the procedure. In addition, patients undergoing electrophysiology studies were required to have narrow complex supraventricular tachycardia or atrial flutter without the need for periprocedural therapeutic anticoagulation. Those older than 75 years  or undergoing atrial fibrillation ablation, ablation of arrhythmias originating from the left heart, or atrial or ventricular tachycardia ablations were excluded. Patients undergoing TAVR or BAV were required to have transfemoral access for the TAVR or BAV, and those with a EuroScore II >20 were excluded. 

The study protocol was approved by the New Zealand multiregion ethics committee, and all study subjects provided written, informed consent prior to participation.

Procedure. Prior to the procedure, subjects underwent a physical exam, transthoracic echocardiogram (TTE), and a review of medications. After the procedure, a review of any potential periprocedural adverse events and a follow-up TTE were performed, and periprocedural medications were recorded. The Tempo lead was inserted under fluoroscopic guidance (Figures 2 and 3) according to the manufacturer’s instructions for use. There were no protocol-driven medication requirements. 

Subjects underwent a follow-up evaluation immediately post procedure and at 24 ± 8 hours after Tempo lead removal. At the time of 24-hour follow-up, an echocardiogram was performed to confirm that no new pericardial effusion (>mild) or tamponade was present. If a subject, for any reason, did not undergo the 24-hour post-lead removal echocardiogram, a postprocedural safety endpoint assessment occurred in lieu of the echocardiogram. Additionally, review at 30 ± 7 days post lead removal was conducted to further determine whether any device-related adverse events had occurred. A clinical events committee comprised three independent physicians who reviewed and adjudicated all serious adverse events and adverse events potentially attributable to the Tempo lead. 

Statistical analysis. This was a safety and technical feasibility study. Results are depicted as mean ± standard deviation. All comparisons were descriptive in nature. Due to the nature of this study, there were no site minimum or maximum enrollment limits.

Results

Baseline data. Of the 25 patients enrolled in the Tempo lead study, a total of 15 (60%) were female. Mean patient age was 64.6 ± 17 years, with a younger population undergoing EP procedures (48.6 ± 9.0 years; n = 11), compared with aortic valve procedures (77.2 ± 9.3 years; n = 14). Mean patient height was 167 ± 9 cm (range, 147-184 cm) and mean weight was 81 ± 22 kg (range, 36-125 kg). Mean left ventricular ejection fraction was 57 ± 11%. Baseline mitral regurgitation was deemed mild in 14 patients (56%), moderate in 5 patients (20%), and absent in the remaining 6 patients (24%). Likewise, baseline tricuspid regurgitation was deemed mild in 16 patients (64%), moderate in 3 patients (12%), and absent in 5 patients (20%).

A pericardial effusion (trace/mild) was present in 4 patients (16%) at baseline. Ten patients (40%) had conduction abnormalities or bradyarrhythmias noted at baseline, including sinus bradycardia (n = 2), first degree atrioventricular block (n = 2), and left bundle-branch block (n = 1). Additional comorbidities included heart failure (n = 4), previous myocardial infarction (n = 3), diabetes (n = 2), and previous smoking (n = 9).

Baseline TTE was performed in all patients, with 23 patients receiving the TTE <30 days before the procedure (mean, 3.8 ± 5.9 days before the procedure) and 2 patients receiving TTE at 37 days and 74 days before the procedure.

Safety. The safety endpoint was met, with all 25 patients free from pericardial effusion requiring intervention and/or clinical and/or echocardiographic evidence of cardiac tamponade following placement of and attributable to the Tempo lead. There were no new pericardial effusions or changes in pre-existing effusions noted in the study, and none required intervention.

During the 30-day follow-up period, there were 15 adverse events in 10 patients, of which 6 were considered serious adverse events. None were considered device-related events by either the investigators or the clinical events committee. 

Technical feasibility. Technical feasibility, defined as the ability of the Tempo lead to access the right ventricle and achieve pace capture, was met in 23 patients. In the other 2 patients, the lead was not successfully positioned due to unsuitable anatomy. One patient was very small (height 141 cm, weight 36 kg), with a small right heart, and the other patient had a very narrow angle from the inferior vena cava to the right ventricle. 

Transfemoral venous access was used in 24 patients, with 1 patient undergoing internal jugular vein access. For the 23 successful patients, the pacing threshold was 0.70 ± 0.53 mA (range, 0.2 to 2.1 mA). Immediately post procedure, the threshold was 0.75 ± 0.56 mA (range, 0.2 to 2.1 mA). The average change in threshold from before to immediately post procedure was 0.05 ± 0.04 mA (range, -0.8 to 1.2 mA), with 15 pace-capture thresholds (65%) remaining unchanged or decreasing in value (range, -0.8 to 0 mA) and 8 pace-capture thresholds (35%) increasing in value (range, 0.1 to 1.2 mA). 

Patient follow-up. At follow-up evaluation 24 hours after lead removal, an echocardiogram found no new or increased effusion size, compared with preprocedure echo (n = 23). No patient had new or increased tricuspid regurgitation severity; 1 patient had a decrease from “moderate” at baseline to “trivial” at follow-up.

There was no incidence of failure to pace with the Tempo lead, including 23 patients who underwent rapid pacing. In the 5 patients with continued postprocedural use of the Tempo lead, there was no loss of capture detected. 

The range of implant time of the Tempo lead was 22 minutes to 5 days. Four of the 5 patients with continued Tempo lead use had the lead in for >24 hours. The mean 24-hour pacing threshold was 1.15 ± 0.4 mA. One patient had the lead in for 5 days, and was intermittently pacing dependent while ambulatory. Daily pacing thresholds were 0.8 mA, 0.8 mA, 1.0 mA, 1.5 mA, and 1.5 mA from days 1 through 5, respectively.

During the index procedure, none of the 23 patients had lead dislodgment or other device failure; lead removal was free of complications in all patients.

Discussion

This first-in-human study demonstrates the safety and technical feasibility of the Tempo lead in human subjects requiring temporary intracardiac pacing. No patient developed a new or increased pericardial effusion, and there were no failures to pace, no arrhythmias attributable to the Tempo lead, and no device-related adverse events.

The Tempo lead successfully accessed the right ventricle and achieved pace capture in the great majority of patients, with the only challenges coming in those with a small right heart and a narrow angle from the inferior vena cava into the right ventricle. The pacing thresholds were all well within the clinically acceptable range, and rapid pacing was consistently achieved, with no loss of capture. Pacing threshold stability throughout the temporary implant period was demonstrated, with satisfactory pacing thresholds at all times.

Experience from the last 40 years has found that temporary transvenous pacing leads are associated with both a high failure rate and frequent serious complications. As the most reliable point of myocardial contact, the distal tip of standard temporary pacing leads has consisted of either a stainless-steel or platinum-iridium electrode. This rigid tip has led to a clinically significant cardiac perforation rate of up to 4% in some studies.^1-6 Moreover, standard temporary leads do not include a myocardial fixation mechanism and have been associated with rates of dislodgment and loss of pace capture in the range of 10%-37%.^1-6 Because most complications occur after, rather than during, the procedure, it is likely that the mechanism reflects limitations of the pacing-lead technology rather than an operator-related cause. ^1-6 

Temporary pacing leads utilizing a screw tip for fixation have exhibited a dislodgment rate of 6%, compared with approximately 1% for permanent active-fixation leads.^11,13 This disparity may be due to the different clinical settings in which temporary and permanent leads are placed. Permanent leads are secured to a subcutaneous permanent generator and develop chronic scar tissue over time, which stabilizes the tip electrode. Temporary leads are prone to dislodgment forces, as they are connected to an external pacemaker generator and are generally removed prior to the development of scar tissue (<1 week). Of greater concern, temporary screw-in leads have been associated with a prohibitively high perforation rate of up to 23%.¹¹ 

The Tempo lead seeks to resolve this unmet need with several novel features. First, a soft polymeric radiopaque tip was designed to reduce the risk of myocardial perforation while providing the operator direct and immediate visual feedback of tissue contact under fluoroscopy. Second, using an external handle-delivery system, two stabilizer loops can be deployed from within the lead via a side port. Deployment of these stabilizing loops into the myocardium is facilitated by a side-mounted balloon that enhances wall apposition in the right ventricle (Figures 1 and 2). These stabilizers are designed to provide atraumatic myocardial fixation via an arcuate spring loop, and constitute the first novel method of pacing-lead fixation entering clinical use in over 30 years. 

Historically, surgical aortic valve replacement has relied upon surgically placed temporary epicardial pacing leads to support perioperative conduction disturbances. With the rapid shift to TAVR worldwide, there has been a move from the use of epicardial to transvenous temporary pacing. Complications of standard temporary transvenous pacing leads have been documented in TAVR literature, and contribute to postprocedural mortality and morbidity.^7-10 Temporary pacing leads serve important procedural roles in TAVR procedures, including support of periprocedural conduction disturbances as well as rapid pacing for deployment of balloon-expandable valves. ^14,15 Stable pace capture is paramount, as is avoidance of cardiac perforation in anticoagulated patients. 

Study limitations. A relatively small number of patients had prolonged Tempo lead implantation in the present study. However, of the 4 who had continued and successful use of the lead beyond 24 hours, 1 patient had it in place while ambulant over 5 days with no loss of capture and a final pacing threshold of 1.5 mA. 

Conclusion

This first-in-human study demonstrates the safety and technical feasibility of the Tempo lead for intraprocedural and postprocedural pacing support of TAVR and electrophysiology procedures. The safety and enhanced pacing stability of the lead might allow early ambulation of patients, especially in a non-intensive care unit setting, with its attendant cost savings.¹⁶ Because periprocedural conduction disturbances after TAVR may resolve over time,^17,18 a concept of watchful waiting with temporary pacing support prior to the decision for permanent pacemaker implantation may gain more emphasis with TAVR growth into intermediate-risk and low-risk populations. 

Clinical Perspective

What is known? Complications of current temporary cardiac pacing leads include dislodgment with loss of pace capture, perforation, and arrhythmias. 

What is new? The novel Tempo temporary pacing lead demonstrated safety and technical feasibility in this first-in-human study in patients undergoing TAVR, BAV, or electrophysiology procedures.

What is next? The Tempo lead has the potential to reduce complications caused by existing temporary cardiac pacing leads. In TAVR patients, it may facilitate early postprocedural ambulation and reduction of permanent pacemaker implantation rates. 

References

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From the ¹Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand; and ²Cardiology Department, Waikato Hospital, Hamilton, New Zealand.

Funding: This study was funded by BioTrace Medical, Inc.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript submitted September 27, 2017, final version accepted October 10, 2017. 

Address for correspondence: Associate Professor Mark Webster, Green Lane Cardiovascular Service, Auckland City Hospital, Private Bag 92024, Victoria St. West, Auckland 1142, New Zealand. Email: MWebster@adhb.govt.nz