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Major adverse clinical events associated with implantation of a leadless intracardiac pacemaker

Open AccessPublished:March 10, 2021DOI:https://doi.org/10.1016/j.hrthm.2021.03.015

      Background

      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.

      Keywords

      Introduction

      Leadless intracardiac pacemakers (LICPs) were developed to avoid the complications of traditional transvenous pacing systems.
      • Spickler J.W.
      • Rasor N.S.
      • Kezdi P.
      • et al.
      Totally self-contained intracardiac pacemaker.
      ,
      • Miller M.A.
      • Neuzil P.
      • Dukkipati S.R.
      • Reddy V.Y.
      Leadless cardiac pacemakers.
      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.
      • Reynolds D.
      • Duray G.Z.
      • Omar R.
      • et al.
      A leadless intracardiac transcatheter pacing system.
      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.
      • Reynolds D.
      • Duray G.Z.
      • Omar R.
      • et al.
      A leadless intracardiac transcatheter pacing system.
      ,
      • Ritter P.
      • Duray G.Z.
      • Zhang S.
      • et al.
      The rationale and design of the Micra Transcatheter Pacing Study: safety and efficacy of a novel miniaturized pacemaker.
      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.
      • Hauser R.G.
      • Katsiyiannis W.T.
      • Gornick C.C.
      • Almquist Ak
      • Kallinen L.M.
      Deaths and cardiovascular injuries due to device-assisted implantable cardioverter-defibrillator and pacemaker lead extraction.
      ,
      • Hauser R.G.
      • Abdelhadi R.
      • McGriff D.
      • Retel L.M.
      Deaths caused by the failure of Riata and Riata ST implantable cardioverter-defibrillator leads.
      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.
      U.S. Food and Drug Administration
      MAUDE—Manufacturer and User Facility Device Experience.
      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
      Micra LICPCapSureFixP value
      No. of major adverse events
      Most patients had ≥1 adverse event.
      363960
       Major adverse event
       Death96 (26.4)23 (2.4)<.001
       Tamponade287 (79.1)225 (23.4)<.001
       Perforation without tamponade61 (16.8)731 (76.1)<.001
       Rescue thoracotomy99 (27.3)50 (5.2)<.001
      Repair RV tear75 (20.7)15 (1.6)<.001
      Repair PA tear2 (0.5).075
      Drainage only24 (6.6)35 (3.6).029
       Pericardiocentesis without thoracotomy190 (52.3)195 (20.3)<.001
       Cardiopulmonary resuscitation79 (21.8)11 (1.1)<.001
       Shock/hypotension80 (22.0)56 (5.8)<.001
      Values are given as n (%) unless otherwise indicated.
      LICP = leadless intracardiac pacemaker; PA = pulmonary artery; RV = right ventricle.
      Most patients had ≥1 adverse event.
      Figure thumbnail gr1
      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
      Case no.MDR report keyModelYearEvent description
      15145503Mi2355A2015Hypotension; tamponade; pericardial drain; CPR; expired.
      26393040MC1VR012017Micra recaptured; tamponade; electromechanical dissociation; emergency drainage; expired.
      36853149MC1VR01US2017Micra not yet deployed; asystole; CPR; perforation; tamponade; pericardiocentesis; expired.
      46807354MC1VR01-DELSYS2017Delivery system shifted; contrast in pericardial space; pericardiocentesis; expired.
      56915500MC1VR012017Perforation; surgical repair; expired in surgery.
      66899065MC1VR01US2017Multiple deployments; tines not engaged; contrast in pericardial space; tamponade; surgery to repair perforation; hemorrhagic shock; expired.
      76946542MC1VR012017Delivery system catheter “slipped”; perforation; tamponade; hypotension; surgery to repair; expired.
      87019586MC1VR012017Six deployments; postop cardiopulmonary arrest; tamponade; expired; autopsy revealed Micra in free wall of the RV.
      97206854MC1VR01US2018Repositioned for inadequate thresholds; cardiopulmonary arrest; expired.
      107397728MC1VR01US2018Effusion after first deployment; effusion; redeployed; recaptured; CPR; thoracotomy for RV free-wall perforation; expired postop due to bleeding.
      117397555MC1VR01US2018Patient coded after third positioning; tamponade due to perforation; expired.
      127393654MC1VR01US2018Perforation and tamponade after third deployment; asystole; temporary pacemaker; pericardiocentesis; expired.
      137447193MC1VR01US2018Micra perforation; effusion; tamponade; expired.
      147511855MC1VR012018Perforation during implant; may have occurred after device was released; expired.
      157560927MC1VR01US2018Tamponade during repositioning and recapture; pericardiocentesis; CPR; expired.
      167566399MC1VR01US2018Patient became unresponsive after repositioning; pericardiocentesis; CPR; expired.
      177596573MC1VR012018Micra deployed; patient unresponsive; pericardiocentesis; expired.
      187605884MC1VR012018Micra deployed but dislodged by tether; perforation; pericardiocentesis; CPR; PCPS; RV free-wall tear repaired with bovine patch; postop renal failure; expired.
      197777892MC1VR01US2018Hypotension after Micra deployed and retrieved; tamponade; 1.5 L of blood removed and retransfused; PEA; expired.
      207622701MC1VR01US2018Hypotension after Micra deployed and recaptured; CPR; pericardiocentesis; re-arrested; CPR; expired.
      217797909MC1VR01US2018Multiple deployments; perforation after recapture; tamponade; expired postprocedure.
      227890089MC1VR012018Four attempts to place Micra; difficult recapture; Micra damaged tricuspid valve; Micra removed and transvenous pacemaker implanted; postop shock; PCPS; multiorgan failure; expired.
      237852577MC1VR012018After 3 unsuccessful positionings, Micra removed; tamponade; sternotomy; expired.
      247931669MC1VR01US2018Micra tines not engaged; recaptured and redeployed; perforation; tamponade; PEA; CPR; expired
      257974154MC1VR01US2018Perforation after second Micra deployment/recapture; CPR; pericardiocentesis; expired 3 days postop.
      267909357MC1VR01USMicra 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.
      277986471Not specified2018Micra redeployed; dyspnea postop; pericardiocentesis; appeared stable but expired 6 days postop.
      288112290MC1VR012018Tamponade after implant; CPR; pericardial drain; sepsis; multiorgan failure; expired.
      298169841MC1VR012018Micra dislodged to pulmonary artery; could not be retrieved; expired.
      308200116MC1VR01US2018Hypotension; pericardial effusion without tamponade; VT/VF; PEA; expired during procedure.
      318221641MC1VR01US2018Hypotension after second deployment; perforation; tamponade; expired.
      328228610MC1VR01US2018Hypotension after attempts to implant; perforation; tamponade; pericardiocentesis; CPR; expired.
      338244319MC1VR01US2018Perforation RV before deployment; expired.
      348276338MC1VR01US2019Perforation and tamponade after implant; PEA; pericardiocentesis; CPR; expired.
      358336990MC1VR012019Tamponade during implant after release of device from deployment sheath; expired.
      368348111MC1VR01US2019RV perforation and tamponade after release of device from delivery system; surgical drain; subsequent surgery to repair tear; expired.
      378413425MC1VR012019Unsatisfactory thresholds when deployed; implanted in low septum, possibly near free wall; small heart; postop tamponade; pericardiocentesis; subsequent infection; expired.
      388418543MC1VR01US2019Delivery system in pericardial space before deployment; effusion; pericardiocentesis and window; epicardial pacemaker; expired.
      398471743MC1VR012019Tamponade 2 days after implant; pericardiocentesis; severe hemorrhage; PEA; CPR; expired; autopsy revealed tine perforating anterior wall.
      408497678MC1VR012019Micra repositioned 6 times; hypotension; tamponade; effusion drained; CPR postop day 1; expired 11 days later.
      418503517MC1VR012019Tamponade 2 hours after implant; pericardiocentesis; hypotension; expired.
      428471876MC1VR012019Perforation during implant; tamponade; effusion drained; CPR; surgery to repair tear; expired.
      438522825MC1VR01US2019Micra dislodged to right atrium; device snared and removed; -dual-chamber pacemaker implanted; hypotension; expired 3–4 hours postop.
      448715471MC1VR012019Difficult positioning; contrast seen in pericardial space before deployment; tamponade; pericardial drain; VT/VF; CPR; expired.
      458788659MC1VR01US2019Perforation during implant; expired.
      468806800MC1VR01US2019Hypotension during Micra implant; perforation; pericardiocentesis; expired.
      478855930MC1VR012019Hypotension after implant in RV hinge region; CPR; tamponade; hemorrhage; thoracotomy; expired 4 days postop of multiorgan failure.
      488887013MC1VR01US2019Tamponade after attempting second deployment; pericardiocentesis; CPR; expired.
      498952745MC1VR012019Contrast visible in pericardial space after implant; tamponade; pericardiocentesis; expired.
      509006451MC1VR01US2019Pericardial effusion after attempted implant; pericardial effusion; pericardiocentesis; sternotomy to repair RV perforation; cerebral vascular accident; expired 2 weeks postop.
      519102554MC1VR01US2019Micra deployed 3 times; contrast in pericardial space; hypotension; pericardiocentesis; CPR; ECMO; sternotomy to repair perforation; expired.
      529146085MCVR01US2019Several deployments and recapture; hypotension; pericardial effusion; pericardiocentesis; CPR; expired.
      539218264MC1VR01US2019Atypical bend in delivery system during implant; device deployed and recaptured twice; hypotension; tamponade; pericardial drain; hemorrhage; CPR; expired.
      549231479MC1VR012019Tamponade after implant; expired 2 weeks postop of pulmonary embolus.
      559380055MC1VR01US2019Micra implanted after 3 unsuccessful attempts; tamponade; PEA; expired.
      569541236MC1VR01US2019Perforation after failed apical implant and recapture and redeployment in septum; pericardial drain; CPR; expired.
      579503292MC1VR012019Delivery system moved during implant; tamponade; expired.
      589586114MC1VR01US2020Perforation during implant; hypotension and asystole; CPR; expired.
      599621154MC1VR01US2020Respiratory distress during implant; RVOT perforation; tamponade; pericardiocentesis; shock; expired 1 day postop.
      609719544MC1VR01US2020Tamponade after first deployment; pericardiocentesis; PEA; CPR; expired.
      619818769MC1VR01US2020Perforation during implant; pericardial drain; expired intraop.
      629816835MC1VR01US2020Perforation during implant; CPR; expired.
      639864631MC1VR01US2020Tamponade during implant; hypotension; pericardiocentesis; expired.
      649903177MICRA AV2020Probable sheath perforation; expired.
      659961893MC1AVR12020Perforation during implant; expired.
      6610211305MC1AVR12020Tamponade after unsuccessful deployment; pericardiocentesis and drain; IABP hemorrhage; family declined surgery; expired.
      6710091135MC1AVR12020Perforation and tamponade during implant; pericardiocentesis; IABP; expired.
      6810142351MC1AVR12020Tamponade and PEA 2 hours after implant; expired.
      6910172695MC1VR01US2020Hypotension after deployment; tamponade; CPR; pericardial drain; expired 11 days postop.
      7010137585MC1VR012020Cardiac arrest after third deployment; effusion; pericardial drain; expired.
      7110205432MC1AVR1-DELSYS2020Perforation before deployment; CPR; expired.
      7210239297MC1AVR12020Tamponade following implant; pericardial drain; expired.
      7310245027MC1VR012020Micra deployed and recaptured; tamponade possibly related to delivery catheter; VT; CPR; pericardial drainage; expired.
      7410360989MC1VR01US2020Difficult positioning; perforation; effusion; pericardial drain; CPR; expired.
      7510405421MC1VR012020Tamponade 1 hour after implant; pericardial drain; expired.
      7610481598MC1VR012020Difficult recapture after deployment; TPM; tamponade postimplant; expired.
      7710536114MC1AVR12020Delivery system perforation; hypotension; pericardiocentesis and drain; implant completed; expired.
      7810518485MC1VR012020Micra implanted in apex after failed septal placement; pericardial effusion and drainage; device redeployed to septum; CPR; expired.
      7910741175MC1VR012020Difficult Micra placement; recaptured; tamponade; pericardial drainage; severe tricuspid regurgitation and right heart failure; ischemic bowel; expired.
      8010747582MC1AVR12020Perforation during attempted implant; sternotomy to repair perforation; expired.
      8110827529MC1AVR12020Expired after Micra implant.
      8210873388MC1AVR12020Possible delivery system perforation; tamponade; CPR; expired.
      8310873333MC1AVR12020Asystole and noncapture after implant; CPR; expired.
      8410822296MC1VR012020Apical perforation by delivery system; tamponade; expired.
      8510835523MC1VR012020Difficult repositioning; tamponade; pericardiocentesis; CPR; sternotomy for apex repair; expired 2 hours postop.
      8610913437MC1AVR12020Perforation and tamponade before deployment due to delivery system in RVOT; expired.
      879731723MC1VR01US2020Tamponade during implant; pericardiocentesis; sternotomy to repair perforation; expired.
      8810153269MC1AVR12020Perforation during implant; sternotomy; expired 2 hours postop.
      8910378049MC1AVR12020Hypotension following implant; tamponade; pericardiocentesis; sternotomy to repair RVOT perforation; 1 tine perforating RVOT; PEA; expired.
      9010677086MC1VR01US2020Perforation after system advanced to low septum position; tamponade; pericardiocentesis; sternotomy; expired.
      9110940445MC1AVR12020Intramyocardial staining after first recapture; hypotension after second recapture; tamponade; pericardial drain clotted; PEA; expired.
      9210990929MC1VR012020Perforation and tamponade during implant; device removed; rescue attempted; expired.
      9311046707MC1AVR12020Expired 1 day after implant.
      9411054676MC1AVR12020Perforation after second deployment; tines would not engage during third deployment; contrast in pericardial space; CPR; pericardiocentesis; expired.
      9511054206MC1AVR12020Attempted implant after PCI of left main and LAD; pulseless after third deployment; CPR; expired.
      9611077016MI2355A2020Large pericardial effusion after Micra deployed and recaptured; CPR; tamponade; pericardial drain; expired.
      CPR = cardiopulmonary resuscitation; ECMO = extracorporeal membrane oxygenation; IABP = intra-aortic balloon pump; intraop = intraoperative; LAD = left anterior descending coronary artery; MDR = medical device report; PCI = percutaneous coronary intervention; PCPS = percutaneous cardiopulmonary support; PEA = pulseless electrical activity; postop = postoperative; RV = right ventricle; RVOT = right ventricular outflow tract; TPM = transvenous pacemaker; VF = ventricular fibrillation; VT = ventricular fibrillation.
      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/shock20 (20.8)60 (22.4).850
      Cardiac tamponade75 (78.1)214 (80.1).784
      Micra repositioned during implant36 (37.5)72 (27.0).071
      Delivery system problems13 (13.5)32 (12.0).829
      Thoracotomy or sternotomy18 (18.8)81 (30.3).040
      Perforation/tear repaired11 (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 keyModelYearEvent description
      153631365076-582015Chest pain several days after CapSureFix implant; re-presented 2 days later; tamponade; pericardium drained—hemorrhage; expired.
      2558729850762016Expired during implant.
      356678975076-652016Lead implanted; CPR; expired.
      458487835076-522016Hypotension after implant; tamponade; pericardiocentesis; PCPS; DIC; expired.
      559954265076-522016Lead repositioned; tamponade; pericardiocentesis; expired 3 days postop.
      661255415076-522016Lead perforated during implant; coded postop; PEA; expired.
      765474405076-582017Perforation during implant; expired.
      865529975076-522017Perforation during reposition; tamponade; pericardiocentesis; expired postop.
      965645935076-582017Perforation during implant; hypotension; pericardial drainage; hemorrhage; family declined surgery; expired.
      1066299485076-522017Multiple repositionings; postop hypotension; loss of capture; effusion; unsuccessful pericardiocentesis; CPR; expired.
      1169457485076-582017Postop perforation; effusion; tamponade; pericardial drainage; expired.
      1270388185076-522017Perforation during implant; tamponade; expired 4 days postop.
      1371349315076-582017Perforation during implant; pericardiocentesis; transfused; expired.
      1473658175076-522018Tamponade 2 days after implant; expired.
      1577373075076-582018Perforation after placement difficulty; lead replaced; expired.
      1681073955076-522018Hypotension and tamponade after lead placement; expired.
      1782085595076-582018Perforation and tamponade after lead perforation; expired.
      1882507295076-522018Perforation and tamponade after lead repositioned; CPR; pericardiocentesis drained 1100 mL of blood; PEA; expired.
      1984141265076-522019Perforation during implant; expired.
      2085198675076-582019Perforation and pericardial effusion; stroke; expired.
      2186429455076-522019Hypotension and cardiac arrest during implant; pericardial drainage minimal due to clotting; surgical intervention judged impossible; expired.
      2286777805076-522019Difficult positioning; perforation; tamponade; CPR; expired.
      23110757304076-582020Perforation 1 day post lead insertion; expired.
      CPR = cardiopulmonary resuscitation; DIC = disseminated intravascular coagulation; PCPS = percutaneous cardiopulmonary support; other abbreviations as in Table 2.

      Discussion

      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.
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      Morbidity and mortality in patients precluded for transvenous pacemaker implantation: experience with a leadless pacemaker.
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      A leadless pacemaker in the real-world setting: the Micra Transcatheter Pacing System Post-Approval Registry.
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      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.
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      Troubleshooting in PM Leadless: how to manage an indissoluble knot.
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      • et al.
      Leadless pacemaker tether failure during recapture attempt leading to device embolization.
      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.
      • Reynolds D.
      • Duray G.Z.
      • Omar R.
      • et al.
      A leadless intracardiac transcatheter pacing system.
      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),
      • Reynolds D.
      • Duray G.Z.
      • Omar R.
      • et al.
      A leadless intracardiac transcatheter pacing system.
      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.
      • Reynolds D.
      • Duray G.Z.
      • Omar R.
      • et al.
      A leadless intracardiac transcatheter pacing system.
      The Nanostim LICP has been evaluated in 3 clinical trials that included 1029 patients.
      • Reddy V.Y.
      • Knops R.E.
      • Sperzel J.
      • et al.
      Permanent Leadless cardiac pacing: results of the LEADLESS trial.
      • Reddy V.Y.
      • Exner D.V.
      • Cantillon D.J.
      • et al.
      Percutaneous implantation of an entirely intracardiac leadless pacemaker.
      • Sperzel J.
      • Defaye P.
      • Delnoy P.-P.
      • et al.
      Primary safety results from the LEADLESS Observational Study.
      In the 33-patient LEADLESS trial, 1 patient died of a stroke after rescue surgery for perforation and tamponade during implant.
      • Reddy V.Y.
      • Knops R.E.
      • Sperzel J.
      • et al.
      Permanent Leadless cardiac pacing: results of the LEADLESS 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%).
      • Reddy V.Y.
      • Exner D.V.
      • Cantillon D.J.
      • et al.
      Percutaneous implantation of an entirely intracardiac leadless pacemaker.
      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.
      • Sperzel J.
      • Defaye P.
      • Delnoy P.-P.
      • et al.
      Primary safety results from the LEADLESS Observational Study.
      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.

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