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Leadless intracardiac pacemakers were developed to avoid the complications of transvenous pacing systems. The Medtronic Micra™ transcatheter pacemaker is one such system. We found an unexpected number of major adverse clinical events (MACE) in the Food and Drug Administration’s Manufacturers and User Facility Device Experience (MAUDE) database associated with Micra implantation.
Objective
The purpose of this study was to describe these MACE and compare them to implant procedure MACE in MAUDE for Medtronic CapSureFix™ active-fixation transvenous pacing leads.
Methods
During January 2021, we queried the MAUDE database for reports of MACE for Micra pacemakers and CapSureFix leads using the simple search terms “death,” “tamponade,” and “perforation.” Reports from 2016–2020 were included.
Results
The search identified 363 MACE for Micra and 960 MACE for CapSureFix leads, including 96 Micra deaths (26.4%) vs 23 CapSureFix deaths (2.4%) (P <.001); 287 Micra tamponades (79.1%) vs 225 tamponades for CapSureFix (23.4%) (P <.001); and 99 rescue thoracotomies for Micra (27.3%) vs 50 rescue thoracotomies for CapSureFix (5.2%) (P <.001). More Micra patients required cardiopulmonary resuscitation (21.8% vs 1.1%) and suffered hypotension or shock (22.0% vs 5.8%) than CapSureFix recipients (P <.001). Micra patients were more likely to survive a myocardial perforation or tear if they had surgical repair (P = .014).
Conclusion
Micra leadless pacemaker implantation may be complicated by myocardial and vascular perforations and tears that result in cardiac tamponade and death. We estimate the incidence is low (<1%). Rescue surgery to repair perforations may be lifesaving. MACE are significantly less for implantation of CapSureFix transvenous ventricular pacing leads.
The Micra™ transcatheter pacing system (Medtronic, Inc., Minneapolis, MN) is a 2016 Food and Drug Administration (FDA)–approved LICP that is implanted in the right ventricle (RV). The pivotal clinical trial reported a high rate of implant success and a safety profile similar to that of transvenous pacemakers.
We found an unexpected number of procedural deaths and surgical complications involving the Micra LICP that the manufacturer has reported to the FDA and are publicly available in the FDA’s online Manufacturers and User Facility Device Experience (MAUDE) database. The purpose of this study was to describe these major adverse clinical events (MACE) and to compare them to similar events in MAUDE for Medtronic’s CapSureFix™ transvenous active-fixation ventricular pacing leads.
Methods
Study design
This was a 5-year (2016–2020) retrospective study comparing MACE in the FDA’s MAUDE database for the Micra LICP and CapSureFix ventricular pacing lead that occurred at implant or during the first 30 days after implant. The CapSureFix lead was chosen for comparison because it has an extendable–retractable fixation mechanism, it is widely available, and during the study an estimated 1–2 million of the leads were implanted in the ventricle worldwide. Furthermore, it is likely that Micra implanters also implant CapSureFix leads. CapSureFix leads implanted in the right atrium were excluded.
Devices and implant procedure
The Micra VR and Micra AV LICP models and the technique for implantation have been described previously.
Briefly, the 20.1F Micra LICP is mounted in a cup on a steerable catheter that is advanced into the RV. The LICP is deployed and fixated by retracting the cup and allowing the nitinol tines to penetrate the endomyocardium. Once fixation is verified, the threshold, impedance, and R-wave amplitude are measured. When the LICP is in a stable and electrically adequate position, the steerable catheter is removed.
The 5.7F–6.9F CapSureFix transvenous bipolar pacing lead models 4076, 5076, and 5086 have an electrically active steroid-eluting extendable–retractable helical fixation screw.
FDA MAUDE database
The MAUDE database contains reports of adverse events involving marketed medical devices that are reported to US manufacturers by users worldwide; thus, it captures “real-world” events.
MAUDE reports do not provide information on the experience, training, or location of the implanting physician or center. Medical devices that remain implanted or have been explanted are included. MAUDE medical device reports (MDRs) are available for the previous 10 years at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfmaude/search.cfm. Manufacturers must submit reports when they learn that a device may have caused or contributed to a death or serious injury, or has malfunctioned.
Because the Nanostim LICP (Abbott, Abbott Park, IL) is not marketed, the manufacturer is not required to submit MAUDE reports.
Because MAUDE data are de-identified and in the public domain, neither informed consent nor institutional review board approval was required for this study. During January 2021, we queried the MAUDE database for reports of MACE for Micra and CapSureFix using the simple search terms “death,” “tamponade,” and “perforation.” Reports that were posted from 2016–2020 were included in the study.
Statistical analysis
Discrete variables are reported as count and percentage, and were analyzed using the Pearson χ2 or Fisher exact test, as appropriate. R Version 3.6.0 (R Foundation for Statistical Computing, Austria) in R Studio Version 1.1.463 (R Studio, Inc.) were used in the analysis.
Results
The MAUDE search identified 363 MACE involving Micra LICPs and 960 MACE involving CapSureFix ventricular leads that were reported to the FDA from 2016–2020 (Table 1 and Figure 1). Of these, approximately one-half were implanted in the United States. There were 11.0 times more deaths and 3.4 times more cases of acute cardiac tamponade for Micra implants compared to CapSureFix ventricular lead placements (P <.001). Significantly more Micra patients required rescue surgery to repair myocardial and vascular perforations and tears than CapSureFix implants (P <.001). Similarly, more Micra patients required cardiopulmonary resuscitation and suffered hypotension or shock during implantation than CapSureFix recipients (P <.001).
Table 1Major adverse events associated with implantation of the Micra LICP and CapSureFix transvenous active-fixation ventricular pacing lead
Figure 1Annual deaths and serious injuries associated with implantation of the Micra leadless intracardiac pacemaker (A) and the CapSureFix active-fixation transvenous ventricular pacing lead (B).
Table 2 provides details for 96 deaths associated with Micra implantation. The hallmark of Micra perforation was abrupt circulatory collapse and acute cardiac tamponade caused by myocardial tears measuring up to 2.5 cm. In some cases, these tears resulted in life-threatening hemorrhage. The locations of tears observed in Micra patients who had surgical repair were anterior wall 7; free wall 6; apex 4; inferior wall 2; right atrium 2; pulmonary artery 2; and inferior vena cava 1. RV free-wall tears were the most common tears described in patients who expired (Table 2) and were described in 9 patients who survived. Of the 14 patients who had RV free-wall tears, 8 had surgical repair and 6 of them survived.
Table 2Deaths associated with Micra leadless intracardiac pacemaker implantation
Micra deployed but dislodged by tether; perforation; pericardiocentesis; CPR; PCPS; RV free-wall tear repaired with bovine patch; postop renal failure; expired.
19
7777892
MC1VR01US
2018
Hypotension after Micra deployed and retrieved; tamponade; 1.5 L of blood removed and retransfused; PEA; expired.
20
7622701
MC1VR01US
2018
Hypotension after Micra deployed and recaptured; CPR; pericardiocentesis; re-arrested; CPR; expired.
21
7797909
MC1VR01US
2018
Multiple deployments; perforation after recapture; tamponade; expired postprocedure.
22
7890089
MC1VR01
2018
Four attempts to place Micra; difficult recapture; Micra damaged tricuspid valve; Micra removed and transvenous pacemaker implanted; postop shock; PCPS; multiorgan failure; expired.
23
7852577
MC1VR01
2018
After 3 unsuccessful positionings, Micra removed; tamponade; sternotomy; expired.
24
7931669
MC1VR01US
2018
Micra tines not engaged; recaptured and redeployed; perforation; tamponade; PEA; CPR; expired
25
7974154
MC1VR01US
2018
Perforation after second Micra deployment/recapture; CPR; pericardiocentesis; expired 3 days postop.
26
7909357
MC1VR01US
Micra deployed in midseptum; tether cut and catheter removed; hypotension; pericardiocentesis removed 100 mL of blood; sternotomy revealed 2.5-cm laceration in apex and 2.5-cm laceration in RVOT; repaired; expired.
27
7986471
Not specified
2018
Micra redeployed; dyspnea postop; pericardiocentesis; appeared stable but expired 6 days postop.
28
8112290
MC1VR01
2018
Tamponade after implant; CPR; pericardial drain; sepsis; multiorgan failure; expired.
29
8169841
MC1VR01
2018
Micra dislodged to pulmonary artery; could not be retrieved; expired.
30
8200116
MC1VR01US
2018
Hypotension; pericardial effusion without tamponade; VT/VF; PEA; expired during procedure.
31
8221641
MC1VR01US
2018
Hypotension after second deployment; perforation; tamponade; expired.
32
8228610
MC1VR01US
2018
Hypotension after attempts to implant; perforation; tamponade; pericardiocentesis; CPR; expired.
33
8244319
MC1VR01US
2018
Perforation RV before deployment; expired.
34
8276338
MC1VR01US
2019
Perforation and tamponade after implant; PEA; pericardiocentesis; CPR; expired.
35
8336990
MC1VR01
2019
Tamponade during implant after release of device from deployment sheath; expired.
36
8348111
MC1VR01US
2019
RV perforation and tamponade after release of device from delivery system; surgical drain; subsequent surgery to repair tear; expired.
37
8413425
MC1VR01
2019
Unsatisfactory thresholds when deployed; implanted in low septum, possibly near free wall; small heart; postop tamponade; pericardiocentesis; subsequent infection; expired.
38
8418543
MC1VR01US
2019
Delivery system in pericardial space before deployment; effusion; pericardiocentesis and window; epicardial pacemaker; expired.
39
8471743
MC1VR01
2019
Tamponade 2 days after implant; pericardiocentesis; severe hemorrhage; PEA; CPR; expired; autopsy revealed tine perforating anterior wall.
40
8497678
MC1VR01
2019
Micra repositioned 6 times; hypotension; tamponade; effusion drained; CPR postop day 1; expired 11 days later.
41
8503517
MC1VR01
2019
Tamponade 2 hours after implant; pericardiocentesis; hypotension; expired.
42
8471876
MC1VR01
2019
Perforation during implant; tamponade; effusion drained; CPR; surgery to repair tear; expired.
43
8522825
MC1VR01US
2019
Micra dislodged to right atrium; device snared and removed; -dual-chamber pacemaker implanted; hypotension; expired 3–4 hours postop.
44
8715471
MC1VR01
2019
Difficult positioning; contrast seen in pericardial space before deployment; tamponade; pericardial drain; VT/VF; CPR; expired.
45
8788659
MC1VR01US
2019
Perforation during implant; expired.
46
8806800
MC1VR01US
2019
Hypotension during Micra implant; perforation; pericardiocentesis; expired.
47
8855930
MC1VR01
2019
Hypotension after implant in RV hinge region; CPR; tamponade; hemorrhage; thoracotomy; expired 4 days postop of multiorgan failure.
48
8887013
MC1VR01US
2019
Tamponade after attempting second deployment; pericardiocentesis; CPR; expired.
49
8952745
MC1VR01
2019
Contrast visible in pericardial space after implant; tamponade; pericardiocentesis; expired.
50
9006451
MC1VR01US
2019
Pericardial effusion after attempted implant; pericardial effusion; pericardiocentesis; sternotomy to repair RV perforation; cerebral vascular accident; expired 2 weeks postop.
51
9102554
MC1VR01US
2019
Micra deployed 3 times; contrast in pericardial space; hypotension; pericardiocentesis; CPR; ECMO; sternotomy to repair perforation; expired.
52
9146085
MCVR01US
2019
Several deployments and recapture; hypotension; pericardial effusion; pericardiocentesis; CPR; expired.
53
9218264
MC1VR01US
2019
Atypical bend in delivery system during implant; device deployed and recaptured twice; hypotension; tamponade; pericardial drain; hemorrhage; CPR; expired.
54
9231479
MC1VR01
2019
Tamponade after implant; expired 2 weeks postop of pulmonary embolus.
55
9380055
MC1VR01US
2019
Micra implanted after 3 unsuccessful attempts; tamponade; PEA; expired.
56
9541236
MC1VR01US
2019
Perforation after failed apical implant and recapture and redeployment in septum; pericardial drain; CPR; expired.
57
9503292
MC1VR01
2019
Delivery system moved during implant; tamponade; expired.
58
9586114
MC1VR01US
2020
Perforation during implant; hypotension and asystole; CPR; expired.
59
9621154
MC1VR01US
2020
Respiratory distress during implant; RVOT perforation; tamponade; pericardiocentesis; shock; expired 1 day postop.
60
9719544
MC1VR01US
2020
Tamponade after first deployment; pericardiocentesis; PEA; CPR; expired.
61
9818769
MC1VR01US
2020
Perforation during implant; pericardial drain; expired intraop.
62
9816835
MC1VR01US
2020
Perforation during implant; CPR; expired.
63
9864631
MC1VR01US
2020
Tamponade during implant; hypotension; pericardiocentesis; expired.
64
9903177
MICRA AV
2020
Probable sheath perforation; expired.
65
9961893
MC1AVR1
2020
Perforation during implant; expired.
66
10211305
MC1AVR1
2020
Tamponade after unsuccessful deployment; pericardiocentesis and drain; IABP hemorrhage; family declined surgery; expired.
67
10091135
MC1AVR1
2020
Perforation and tamponade during implant; pericardiocentesis; IABP; expired.
68
10142351
MC1AVR1
2020
Tamponade and PEA 2 hours after implant; expired.
69
10172695
MC1VR01US
2020
Hypotension after deployment; tamponade; CPR; pericardial drain; expired 11 days postop.
70
10137585
MC1VR01
2020
Cardiac arrest after third deployment; effusion; pericardial drain; expired.
71
10205432
MC1AVR1-DELSYS
2020
Perforation before deployment; CPR; expired.
72
10239297
MC1AVR1
2020
Tamponade following implant; pericardial drain; expired.
73
10245027
MC1VR01
2020
Micra deployed and recaptured; tamponade possibly related to delivery catheter; VT; CPR; pericardial drainage; expired.
In 108 patients(29.6%), the Micra LICP was repositioned due to insecure fixation or inadequate threshold or R-wave measurements. Of these, 67 (62.0%) were repositioned more than once, and 11 (10.2%) were repositioned >3 times.
Delivery system problems were reported in 48 patients, including 12 perforations resulting in cardiac tamponade. Other issues included maneuverability, slippage, and difficulty recapturing the pulse generator.
Of 23 patients who developed cardiac tamponade postprocedure, 13 did so within the first hour, 7 within 3–5 hours, and 3 within 12–48 hours. Five of these patients died, including 3 who developed tamponade during the first postoperative hour and 2 who developed tamponade 2 hours postprocedure.
Table 3 compares Micra patients who died to those who survived. Clinically, the 2 groups were similar, including incidence of tamponade and shock or hypotension, and the proportion of patients whose Micra implants required repositioning or were associated with delivery system problems. The differences between the groups were in treatment: significantly more patients survived if they underwent surgical repair (P = .014).
Table 3Comparison of patients who died and those who survived major adverse events associated with implantation of the Micra leadless intracardiac pacemaker
Deaths (N = 96)
Survivors (N = 267)
P value
Hypotension/shock
20 (20.8)
60 (22.4)
.850
Cardiac tamponade
75 (78.1)
214 (80.1)
.784
Micra repositioned during implant
36 (37.5)
72 (27.0)
.071
Delivery system problems
13 (13.5)
32 (12.0)
.829
Thoracotomy or sternotomy
18 (18.8)
81 (30.3)
.040
Perforation/tear repaired
11 (11.5)
64 (24.0)
.014
Values are given as n (%) unless otherwise indicated.
Details of deaths associated with implantation of CapSureFix transvenous active-fixation ventricular leads are provided in Table 4. One-fourth of cases involved difficult lead placement and/or repositioning. The majority of patients who died had cardiac tamponade and underwent pericardiocentesis or surgical drainage.
Table 4Deaths associated with CapSureFix transvenous right ventricular lead implantation
Case no.
MDR report key
Model
Year
Event description
1
5363136
5076-58
2015
Chest pain several days after CapSureFix implant; re-presented 2 days later; tamponade; pericardium drained—hemorrhage; expired.
2
5587298
5076
2016
Expired during implant.
3
5667897
5076-65
2016
Lead implanted; CPR; expired.
4
5848783
5076-52
2016
Hypotension after implant; tamponade; pericardiocentesis; PCPS; DIC; expired.
5
5995426
5076-52
2016
Lead repositioned; tamponade; pericardiocentesis; expired 3 days postop.
6
6125541
5076-52
2016
Lead perforated during implant; coded postop; PEA; expired.
7
6547440
5076-58
2017
Perforation during implant; expired.
8
6552997
5076-52
2017
Perforation during reposition; tamponade; pericardiocentesis; expired postop.
9
6564593
5076-58
2017
Perforation during implant; hypotension; pericardial drainage; hemorrhage; family declined surgery; expired.
10
6629948
5076-52
2017
Multiple repositionings; postop hypotension; loss of capture; effusion; unsuccessful pericardiocentesis; CPR; expired.
The results of our study suggest that implantation of the Micra LICP may result in catastrophic myocardial and vascular perforations and tears. These injuries are significantly more likely to cause acute cardiac tamponade and death than those that occur during implantation of the CapSureFix transvenous ventricular pacing lead. Although pericardiocentesis may provide immediate relief of hemopericardium, our findings suggest that emergency surgery to repair a myocardial or vascular perforation is potentially lifesaving. Consequently, we recommend Micra implants be performed in hospitals capable of performing emergency cardiothoracic surgery.
These results are surprising given the paucity of Micra adverse events reported in the literature and the enthusiasm for this technology. A few Micra LICP procedural deaths and complications have been described.
Updated performance of the Micra transcatheter pacemaker in the real-world setting: a comparison to the investigational study and a transvenous historical control.
However, our study is the first to report a large number of procedural MACE, including 96 deaths, associated with Micra implantation. These findings should prompt physicians and regulators to question the assertion that the rate of acute complications is similar for Micra compared to transvenous pacemakers.
The true incidence of MACE for Micra is not known but can be estimated. Although Medtronic has not included Micra data in its product performance reports, we estimate that 70,000–75,000 Micra pacemakers were implanted worldwide in 2020. As 126 MACE occurred in 2020 (Figure 1), the estimated Micra MACE incidence for that year is 0.2%. Even if MACE were underreported by a factor of 5, the incidence would be <1%. Whatever the true incidence, such information is essential if patients are to be informed of the risks of Micra LICP implantation compared to the insertion of a traditional transvenous pacemaker. We encourage the manufacturer to make available all of its relevant Micra safety outcomes data.
The Micra system has performed reliably, with few reported product problems.
No MACE in this study was caused by an identified device defect or alleged by a health care professional. Accordingly, in addition to a patient’s anatomy and comorbidities, the potential causes of these MACE must be related to the Micra’s design, the implant procedure, and/or the operator’s skill and experience.
The MAUDE data provide some insights. The pacemaker is affixed to the myocardium by applying tip pressure via the delivery catheter and manually retracting the device cup so that the nitinol tines self-expand into the myocardium. Nearly 30% of implants in our series required redeployment. It is reasonable to infer that these redeployments and refixations increased the risk of perforation. However, the definitive risk of perforation and tamponade due to repositioning and redeployment requires a comparison of patients who did and those who did not suffer this complication. Some perforations occurred when the device first contacted the endomyocardium, and it is possible that modest pressure forced the device through a thin or diseased RV.
It is important to know precisely where the LICP is located in the RV during positioning, deployment, and fixation. The MAUDE data suggest that lack of such knowledge accounted for some MACE. Inadvertent LICP implantation in the RV free wall resulted in 5 deaths and 9 additional perforations. Notably, none of the implants in the pivotal clinical trial were in the RV free wall.
Education programs and techniques to improve LICP placement are needed, and additional studies are required to identify the most suitable RV implant locations.
The MAUDE data raise 2 additional issues: (1) anticoagulation and (2) same day discharge. Massive hemorrhage occurred in some cases and could not be controlled by anticoagulation reversal or emergency surgery. Studies are needed to determine the best approach to managing anticoagulation before and during LICP implantation. In this study, 23 patients (6.3%) developed cardiac tamponade postprocedure and 5 died. In view of this, criteria should be developed and tested to identify patients who can be safely discharged on the day of implantation.
During the Micra Transcatheter Pacing Study (MTPS),
725 subjects underwent attempted implant at 56 centers in 19 countries. One patient died and 13 patients sustained cardiac injuries; these patients tended to be older, female, smaller (lower body mass index), and had a history of myocardial infarction or chronic lung disease. Such patient-specific information is not provided in MAUDE; thus, we cannot exclude the possibility that patients who suffered MACE in our study were at higher risk for complications.
Given the single death in MTPS, it is likely that the unexpected number of deaths observed in our study was related, in part, to operator skill and experience, level of device-specific training, progress on the learning curve, and adherence to the implant protocol. Although Medtronic offers and requires implanting physician training, it is possible that disparities in education programs and mentoring accounted for a number of MACE. In order to make LICP implantation safer, it is important to identify the physician qualifications, requisite training, and procedural volumes that produce the best LICP outcomes.
The number of deaths associated with CapSureFix ventricular lead insertion was higher than expected but significantly lower than in the Micra group. The incidence of CapSureFix lead MACE could not be estimated because the worldwide number of leads implanted in the ventricle could not be determined with certainty. Possibly fewer CapSureFix patients suffered cardiac tamponade or required rescue surgery because the size of the perforations was smaller than those caused by the Micra LICP. It is noteworthy that no procedural deaths occurred in patients who received the CapSureFix lead in the study that served as the historical control group in the Micra pivotal trial.
Of the 526 patients in the LEADLESS II trial, 6.5% had a serious adverse event, including 2 procedure-related deaths and 8 cardiac perforations (1.5%).
The LEADLESS Observational Study, which included 470 subjects, was paused in April 2014 after 2 deaths occurred due to cardiac perforation. A total of 11 perforations (2.3%) were reported upon completion.
Thus, potentially lethal cardiac perforations seem to be the major risk of both Micra and Nanostim implantation.
Study limitations
The true incidences of MACE reported in this study are unknown. It is likely that a number of MACE are not reported to the manufacturer or to the FDA and are not in the MAUDE database. Underreporting may have been more frequent for CapSureFix than Micra because the former is an older product. The search terms may have missed MACE that were filed elsewhere in MAUDE; therefore, we may have underreported the true number of MACE. It also is possible that MAUDE reports contain erroneous narrative information.
Conclusion
Implantation of the Micra LICP may be complicated by myocardial perforations and tears that result in circulatory collapse, acute cardiac tamponade, and death. The true incidence of these MACE is unknown, but we estimate that it is low (<1%). Rescue surgery to repair myocardial and vascular tears may be lifesaving. Device repositioning, RV free-wall implantation, and delivery system difficulties seem to increase the risk of perforation and tamponade. The risk of implanting the CapSureFix transvenous ventricular pacing lead in this study was significantly less than for implantation of the Micra LICP.
Updated performance of the Micra transcatheter pacemaker in the real-world setting: a comparison to the investigational study and a transvenous historical control.
Funding sources: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Disclosures: Dr. Hauser has served on the scientific advisory board of Cardiac Insight Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The story of leadless pacing began some 50 years ago.1,2 Over the past decade, technological advancements, including circuit miniaturizations, improved battery technology and electrodes, and sophisticated fixation mechanisms, have facilitated development.
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