Early Performance of a Miniaturized Leadless Cardiac Pacemaker

The Micra Transcatheter Pacing Study

Philippe Ritter; Gabor Z. Duray; Clemens Steinwender; Kyoko Soejima; Razali Omar; Lluís Mont; Lucas VA Boersma; Reinoud E. Knops; Larry Chinitz; Shu Zhang; Calambur Narasimhan; John Hummel; Michael Lloyd; Timothy Alexander Simmers; Andrew Voigt; Verla Laager; Kurt Stromberg; Matthew D. Bonner; Todd J. Sheldon; Dwight Reynolds

Disclosures

Eur Heart J. 2015;36(37):2510-2519. 

In This Article

Results

Patient recruitment began 5 December 2013 and the 60th 3-month visit accrued on 11 August 2014, triggering evaluation of the early performance objectives. At the time of database closure for this analysis, 140 patients had an attempted implant and all were successfully implanted. The TPS was implanted in these 140 patients in 23 study centres by 37 physicians in 11 countries and were followed to an average of 1.9 ± 1.8 months (range 0–6.5 months). Patients were mostly male (60.7%), of mean age 77.0 ± 10.2 years, height range 144–190 cm, and weight range 41–148 kg (Table 1). The most common primary indications for pacing were atrioventricular (AV) block (66%, or 93 of 140 patients) and symptomatic sinus node dysfunction (29%, or 40 of 140 patients). Nine (6%) patients were not felt to be appropriate for implantation of conventional transvenous lead pacing systems due to a variety of reasons such as compromised venous access, previous infection, and cancer with need for indwelling catheter. Confirmation of appropriate pacemaker operation from the 24 h ambulatory ECG analysis by the trial's data monitoring committee was achieved 3 weeks prior to database closure, enabling pacemaker-dependent patient enrolment. Two pacemaker-dependent patients were subsequently implanted and included in this analysis.

Ninety-one (65%) of the 140 patients received a VVI pacemaker for bradycardia in conjunction with permanent or persistent atrial tachyarrhythmias. Of the remaining 49 patients, 22 had sinus node dysfunction, 19 had AV block, two had sinus node dysfunction plus AV block, and six had other reasons listed for choosing a ventricular pacemaker. In these 49 patients, the predominant reason for TPS selection was identified as 'infrequent pacing expected' (69%) and 'advanced age' (22%). Other reasons included sedentary lifestyle, anatomical limitations, or co-morbidities increasing complication risk.

Implant Procedure Results

The implant success rate was 100% (140/140). Type of anaesthesia, anticoagulation, and use of antibiotics were at the discretion of implanters. Sedation and/or local anaesthesia was applied in 93.6% of patients and general anaesthesia used in 6.4%. No systemic anticoagulation was applied in 36%, and various regimens were used in the other patients (40% received heparin and 24% received another anticoagulation method). An anticoagulation antagonist was used to reverse anticoagulation effects in 16 patients (11%). The mean implant time was 37 ± 21 min (range: 11–154 min) with an average fluoroscopy time of 9 ± 7 min. The majority of attempts were successful upon initial device positioning (59%) or two positioning (22.1%), but the maximum number of attempts in a single patient was 18 deployments (mean ± SD, 2 ± 2). A second device was used in two implants, due to unacceptable electrical measurements. In both cases, electrical measurements with the second device were similar to the measurements of the first device, although ultimately both cases were able to achieve a position with acceptable electrical measurements. While 107 of the 140 devices were placed at the RV apex (76.4%), 33 (24%) were implanted at the anterior septum, mid-septum, or outflow tract (images available in Figure 5). Access site closure was predominantly performed using a suture method (76%), although other methods were observed (such as manual pressure or venotomy occlusion system). The average time to ambulation following the procedure was 13 ± 8 h and the median days from procedure to hospital discharge was 1 day, although day to discharge varied by geography (mean ± SD, 2 ± 2).

Figure 5.

X-rays of various device positions in RAO view. Left panel: apical device placement; Middle panel: mid-septal device placement; Right panel: right-ventricular outflow tract (RVOT) device placement.

Early Safety Performance

There were no USADEs in the 140 patients, thus the safety objective was met with 100% freedom from USADEs at 3 months (95% confidence interval, 94.0–100%; P < 0.0001). Thirty adverse events occurred in 26 patients, all within 17 days of implant (Table 2).

One pericardial effusion was observed in a 90-year-old female who had undergone 18 repositioning because of inappropriate electrical measurements, the highest number of repositioning observed in the study. A pericardial drainage was performed to drain approximately 250 cc of blood, although no tamponade was diagnosed. The same patient experienced an acute myocardial infarction 3 days post-implant and angiography revealed three-vessel coronary artery disease. Transient complete AV block occurred in four patients and resolved within seconds to a few hours. Three cases of transient AV block required pacing via a temporary wire. The fourth resolved with immediate programming to active pacing after device deployment. Each of the four patients experiencing transient AV block had a history of LBBB or prolonged AV conduction (two had second-degree AV block, one had LBBB with first-degree AV block, and one had LBBB). Groin bleeding ('incision site haemorrhage') was observed in three of the 140 patients, and a haematoma in two. None of these events were considered serious, and all cases resolved without invasive intervention. There were two cases of arterial pseudoaneurysms. One of the two events was considered serious and required thrombin injection with prolonged hospitalization. The other pseudoaneurysm was not considered serious and resolved without any invasive intervention. There was no apparent relationship to heparin use or closure method approach in the events which were observed at the groin puncture site. (There was a total of 11 events at the groin puncture site and intravenous heparin was administered in approximately half of the events. A suture method was used for closure in each of these 11 cases except one where only manual pressure was applied). One patient death occurred 139 days post-implant, was not cardiovascular related, and was determined to not be related to the procedure or system.

Early Efficacy Performance

The mean pacing capture threshold at the 3-month visit for the 60 patients measured at 0.24 ms was 0.51 V (95% CI, 0.45–0.56; P < 0.0001), meeting the efficacy objective. In these 60 patients, the mean electrical values for R-wave sensing amplitude, pacing impedance, and pacing capture threshold at 0.24 ms were, respectively: 11.7 ± 4.5 mV, 719 ± 226 ohm, 0.57 ± 0.31 V at implant, 15.6 ± 4.8 mV, 662 ± 133 ohm, 0.48 ± 0.21 V at 1-month, and 16.1 ± 5.2 mV, 651 ± 130 ohm, 0.51 ± 0.22 V at 3-months (Figure 6). All measurements at all visits were within expected ranges. Paired comparison of the 60 patients from implant to 3-month electrical values demonstrated an increase in R-wave amplitude (4.4 mV, P < 0.0001), a decrease in impedance (68 ohms, P = 0.006), and a non-significant decrease in pacing capture threshold (0.06 V, P = 0.057). Rate response was programmed on in 54% (76 out of 140) of patients, programmed to VVIR where an initial testing showed effective rate adaptation to short walking test. Ongoing evaluations in the study will confirm rate response operation via treadmill testing in a subset of subjects.

Figure 6.

Device electrical measures of first 60 patients. A, B, and C display the mean ± SD of the pacing threshold at 0.24 ms, R-wave amplitude, and impedance respectively for all data available from the 60 patients followed to 3 months. The P-value in A is for the comparison of the mean pacing capture threshold to the performance goal of 2.0V. **Significantly different from implant value.

Ambulatory ECG Evaluation

Examination of 24 h ambulatory surface ECG and device electrogram cycle by cycle at the 1-month visit from 25 patients indicated that the device was pacing and sensing as expected. There were no pauses due to inappropriate TPS operation. Additionally, the daily capture threshold testing and hourly threshold confirmation tests were performing as expected.

Longevity Estimation

In 60 patients followed to 3 months, cumulative percent pacing ranged from <1 to >99% with a median of 49% (interquartile range, 10.2–75.1%). Based on device use conditions (e.g. heart rate, pulse width, pacing amplitude, impedance) through 3-months, battery longevity was estimated at an average 12.6 years (range 8.6–14.4 years, Figure 7). This estimate does not include pacemaker-dependent patients and assumes that thresholds remain stable for device lifetime.

Figure 7.

Distribution of expected transcatheter pacing system battery longevity based on device use conditions (% pacing, heart rate, pacing capture thresholds) of first 60 patients through 3 months.

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