TY - JOUR
AU - Marques, Manlio
AB - Introduction Cardiac implantable electronic devices (CIEDs) have become an integral part of brady- and tachy-arrhythmia management over the last seven decades. Most currently used legacy systems consist of a pacemaker (PM) and/or implantable cardioverter defibrillator (ICD) containing all the electronics implanted under the skin in the shoulder region, with a transvenous (TV) lead connecting the device to the heart for signal detection and cardiac stimulation and defibrillation. The TV lead is both the indispensable link to the PM or ICD, as well as the Achilles heel of the system. Over the last decade, this has led to the development of new CIED that can perform with a lead outside of the endovascular space or that do not require a lead at all. As randomized controlled data comparing this new generation CIED to traditional TV devices is scarce, international guidelines so far do not provide strong recommendations on their use. There is however a growing body of evidence supporting their efficacy and safety under various circumstances and in a wide variation of clinical scenarios. This position paper aims to review the underlying evidence and provide practical considerations for optimal use and patient selection for these CIED that are either currently or very close to becoming available. To provide guidance, the acknowledged format of the European Heart Rhythm Association will be used, as provided in Table 1. Table 1 Scientific rationale of recommendationsa Definitions where related to a treatment or procedure . Consensus statement . Symbol . Scientific evidence that a treatment or procedure is beneficial and effective. Requires at least one randomized trial, or is supported by strong observational evidence and authors’ consensus (as indicated by an asterisk). Recommended/indicated General agreement and/or scientific evidence favour the usefulness/efficacy of a treatment or procedure. May be supported by randomized trials based on small number of patients or not widely applicable. May be used or recommended Scientific evidence or general agreement not to use or recommend a treatment or procedure. Should NOT be used or recommended Definitions where related to a treatment or procedure . Consensus statement . Symbol . Scientific evidence that a treatment or procedure is beneficial and effective. Requires at least one randomized trial, or is supported by strong observational evidence and authors’ consensus (as indicated by an asterisk). Recommended/indicated General agreement and/or scientific evidence favour the usefulness/efficacy of a treatment or procedure. May be supported by randomized trials based on small number of patients or not widely applicable. May be used or recommended Scientific evidence or general agreement not to use or recommend a treatment or procedure. Should NOT be used or recommended a This categorization for our consensus document should not be considered as being directly similar to that used for official society guideline recommendations which apply a classification (I–III) and level of evidence (A–C) to recommendations. Open in new tab Table 1 Scientific rationale of recommendationsa Definitions where related to a treatment or procedure . Consensus statement . Symbol . Scientific evidence that a treatment or procedure is beneficial and effective. Requires at least one randomized trial, or is supported by strong observational evidence and authors’ consensus (as indicated by an asterisk). Recommended/indicated General agreement and/or scientific evidence favour the usefulness/efficacy of a treatment or procedure. May be supported by randomized trials based on small number of patients or not widely applicable. May be used or recommended Scientific evidence or general agreement not to use or recommend a treatment or procedure. Should NOT be used or recommended Definitions where related to a treatment or procedure . Consensus statement . Symbol . Scientific evidence that a treatment or procedure is beneficial and effective. Requires at least one randomized trial, or is supported by strong observational evidence and authors’ consensus (as indicated by an asterisk). Recommended/indicated General agreement and/or scientific evidence favour the usefulness/efficacy of a treatment or procedure. May be supported by randomized trials based on small number of patients or not widely applicable. May be used or recommended Scientific evidence or general agreement not to use or recommend a treatment or procedure. Should NOT be used or recommended a This categorization for our consensus document should not be considered as being directly similar to that used for official society guideline recommendations which apply a classification (I–III) and level of evidence (A–C) to recommendations. Open in new tab Leadless cardiac pacemakers Background Leadless cardiac pacemakers (LCPMs) are an emerging alternative to TV-PM1–3 to reduce the complications related to TV leads and subcutaneous generator pockets.4–6 The LCPMs eliminate the risk of pocket infection and haematoma,1,2,7,8 as well as pneumothorax, lead dislodgement, infection, and fracture.9 Conversely, early LCPM studies have shown groin problems and myocardial perforation,1,2,10 patient management at the time of battery depletion is unresolved, first-generation devices only provided VVI-R pacing, while LCPM long-term outcome data are lacking. Details about various LCPM device and studies are provided in Table 2. In the LEADLESS II study,2 Nanostim LCPM implantation was successful in 95.8% of 526 patients, with major adverse events in 6.5% (perforation 1.5%, dislodgement 1.1%). Its successor AVEIR has been successfully implanted in 98% of 200 patients, with 3 cardiac tamponades requiring sternotomy in 2 patients.11 The Micra LCPM showed a 99.2% implant success in the investigational device exemption (IDE) and post-approval registry studies,1,3 and 41–63% lower complication rate (perforation 1.8 and 0.77%), with significantly lower device revision needed compared with a historical TV-PM cohort.9 In the recent Micra CED study,12 adjusted 30-day adverse event rates were similar (7.7 vs. 7.4%, P = 0.49), perforation was more frequent (0.8 vs. 0.4%, P < 0.01), while device-related events were significantly lower (1.4 vs. 2.5% P < 0.001) for LCPM (5746 patients) vs. single-chamber TV-PM (9662 patients). At 2 years, chronic complications were lower [adjusted hazard ratio (HR) 0.69, P < 0.0001], mainly driven by less re-intervention with Micra (adjusted HR 0.62, P = 0.006). Table 2 Summary of leadless trials and device characteristics . LEADLESS II2 . LEADLESS II: Phase 211 . Micra IDE1 . Micra PAR3 . Micra CED12 . Device Nanostim LCPM Aveir LCPM Micra TPS Micra TPS Micra TPS Patients 526 200 725 1817 5764 Follow-up duration 6 months 3.92 months 1 year 1 year 2 years Successful implant 95.8% 98% 99.2% 99.1% N/A Perforation 1.5% 1.5% 1.5% 0.44%a (0.77%) 0.8% Macrodislodgement 1.1% 1% 0 0.06% Elevated threshold 0.8% 0.3% 0.5% Vascular complications 1.2% 1% 0.7% 0.61% 1.2% Volume (cc) 1.0 NN 0.8 Length × width (mm) 42 × 5.9 NN 25.9 × 6.7 Diameter of introducer inner/outer (Fr) 18/21 25/27 23/27 Fixation Screw in helix Screw in helix 4 Tines Autocapture No No Yes Battery Lithium carbon monofluoride Lithium carbon monofluoride Lithium silver vanadium oxide Rate response sensor Blood temperature sensor Blood temperature sensor 3-D axis accelerometer MRI conditionality 1.5 T NN 1.5 and 3T Communication Conductive Conductive Radiofrequency Remote monitoring No No Medtronic carelink . LEADLESS II2 . LEADLESS II: Phase 211 . Micra IDE1 . Micra PAR3 . Micra CED12 . Device Nanostim LCPM Aveir LCPM Micra TPS Micra TPS Micra TPS Patients 526 200 725 1817 5764 Follow-up duration 6 months 3.92 months 1 year 1 year 2 years Successful implant 95.8% 98% 99.2% 99.1% N/A Perforation 1.5% 1.5% 1.5% 0.44%a (0.77%) 0.8% Macrodislodgement 1.1% 1% 0 0.06% Elevated threshold 0.8% 0.3% 0.5% Vascular complications 1.2% 1% 0.7% 0.61% 1.2% Volume (cc) 1.0 NN 0.8 Length × width (mm) 42 × 5.9 NN 25.9 × 6.7 Diameter of introducer inner/outer (Fr) 18/21 25/27 23/27 Fixation Screw in helix Screw in helix 4 Tines Autocapture No No Yes Battery Lithium carbon monofluoride Lithium carbon monofluoride Lithium silver vanadium oxide Rate response sensor Blood temperature sensor Blood temperature sensor 3-D axis accelerometer MRI conditionality 1.5 T NN 1.5 and 3T Communication Conductive Conductive Radiofrequency Remote monitoring No No Medtronic carelink CED, continuous evidence development; IDE, investigational device exemption; PAR, post-approval registry; LCPM, leadless cardiac pacemaker; NN, unknown. a Meeting criteria for major complication. Open in new tab Table 2 Summary of leadless trials and device characteristics . LEADLESS II2 . LEADLESS II: Phase 211 . Micra IDE1 . Micra PAR3 . Micra CED12 . Device Nanostim LCPM Aveir LCPM Micra TPS Micra TPS Micra TPS Patients 526 200 725 1817 5764 Follow-up duration 6 months 3.92 months 1 year 1 year 2 years Successful implant 95.8% 98% 99.2% 99.1% N/A Perforation 1.5% 1.5% 1.5% 0.44%a (0.77%) 0.8% Macrodislodgement 1.1% 1% 0 0.06% Elevated threshold 0.8% 0.3% 0.5% Vascular complications 1.2% 1% 0.7% 0.61% 1.2% Volume (cc) 1.0 NN 0.8 Length × width (mm) 42 × 5.9 NN 25.9 × 6.7 Diameter of introducer inner/outer (Fr) 18/21 25/27 23/27 Fixation Screw in helix Screw in helix 4 Tines Autocapture No No Yes Battery Lithium carbon monofluoride Lithium carbon monofluoride Lithium silver vanadium oxide Rate response sensor Blood temperature sensor Blood temperature sensor 3-D axis accelerometer MRI conditionality 1.5 T NN 1.5 and 3T Communication Conductive Conductive Radiofrequency Remote monitoring No No Medtronic carelink . LEADLESS II2 . LEADLESS II: Phase 211 . Micra IDE1 . Micra PAR3 . Micra CED12 . Device Nanostim LCPM Aveir LCPM Micra TPS Micra TPS Micra TPS Patients 526 200 725 1817 5764 Follow-up duration 6 months 3.92 months 1 year 1 year 2 years Successful implant 95.8% 98% 99.2% 99.1% N/A Perforation 1.5% 1.5% 1.5% 0.44%a (0.77%) 0.8% Macrodislodgement 1.1% 1% 0 0.06% Elevated threshold 0.8% 0.3% 0.5% Vascular complications 1.2% 1% 0.7% 0.61% 1.2% Volume (cc) 1.0 NN 0.8 Length × width (mm) 42 × 5.9 NN 25.9 × 6.7 Diameter of introducer inner/outer (Fr) 18/21 25/27 23/27 Fixation Screw in helix Screw in helix 4 Tines Autocapture No No Yes Battery Lithium carbon monofluoride Lithium carbon monofluoride Lithium silver vanadium oxide Rate response sensor Blood temperature sensor Blood temperature sensor 3-D axis accelerometer MRI conditionality 1.5 T NN 1.5 and 3T Communication Conductive Conductive Radiofrequency Remote monitoring No No Medtronic carelink CED, continuous evidence development; IDE, investigational device exemption; PAR, post-approval registry; LCPM, leadless cardiac pacemaker; NN, unknown. a Meeting criteria for major complication. Open in new tab Currently Micra is the only LCPM commercially available. The Nanostim device is no longer available due to pre-mature battery depletion and occurrence of docking button separation.13 New devices including AVEIR and EMPOWER are currently being implanted and investigated in ongoing new clinical trials (Figure 1). Figure 1 Open in new tabDownload slide Leadless cardiac pacemaker devices: (A) Nanostim, (B) AVEIR, (C) EMPOWER, (D) Micra (reproduced with permission of Medtronic). Implantation: general The LCPM are typically implanted via a usually right femoral venous approach, using dedicated steerable delivery systems with different external sheath diameters (21-F for Nanostim and 27-F for Micra). As data on procedures using steerable femoral sheaths indicate that ultrasound-guided femoral venous puncture may avoid groin complications compared with the conventional approach, it may be useful for LCPM implantation using large bore sheaths.14 Alternative implantation techniques from the jugular vein have been reported. A temporary backup pacing wire may be useful in patients with left bundle branch block in case the right bundle branch is damaged. The optimal area for device deployment is the mid-septum, whereas the free wall of the right ventricle must be avoided due to the risk of perforation. As discrimination of a septal and free-wall position may be difficult using standard X-ray projections in some cases, individualized rather than standard angulations, or additional right ventriculography may facilitate proper positioning. Contrast injection via the delivery system should be considered for confirmation of wall contact (Figure 2). When considering implantation of a subsequent LCPM without extraction of the previous one, cadaver studies indicate that up to three Micra devices could be accommodated simultaneously using traditional pacing locations, and human in vivo studies documented safe implantation of two LCPMs (Table 3).15 Figure 2 Open in new tabDownload slide Left anterior oblique (A) and right anterior oblique (B) X-ray images of LCPM implantation using contrast injection through the delivery catheter system to determine optimal right ventricular positioning and tissue contact. Optimal implantation is to be done in a septal RV position (C). LAO, left anterior oblique; RAO, right anterior oblique. Table 3 Implantation technique and peri-implant management Position statement . Symbol . Evidence . A single dose of intravenous antibiotics should be administered before LCPM implantation, in accordance with ESC guidelines on cardiac pacing and cardiac re-synchronization therapy 17, 18, 20 Ultrasound-guided femoral vein puncture may be used to reduce the risk of vascular complications 14 Contrast injection via the delivery system may be used for confirmation of device position and wall contact EO Additional imaging manoeuvres (individualized X-ray angulations in more directions, right ventriculography) may be used to assess optimal target areas for device implantation and to avoid free-wall implantation EO For LCPM implantation in patients taking VKAs or DOACs, uninterrupted anticoagulation may be used 18, 19, 20, 21 A Heparin-bridging strategy in patients using OAC should not be used 17 Routine post-op antibiotic prophylaxis should not be used 17 Position statement . Symbol . Evidence . A single dose of intravenous antibiotics should be administered before LCPM implantation, in accordance with ESC guidelines on cardiac pacing and cardiac re-synchronization therapy 17, 18, 20 Ultrasound-guided femoral vein puncture may be used to reduce the risk of vascular complications 14 Contrast injection via the delivery system may be used for confirmation of device position and wall contact EO Additional imaging manoeuvres (individualized X-ray angulations in more directions, right ventriculography) may be used to assess optimal target areas for device implantation and to avoid free-wall implantation EO For LCPM implantation in patients taking VKAs or DOACs, uninterrupted anticoagulation may be used 18, 19, 20, 21 A Heparin-bridging strategy in patients using OAC should not be used 17 Routine post-op antibiotic prophylaxis should not be used 17 DOAC, direct oral anticoagulation; LCPM, leadless cardiac pacemaker; OAC, oral anticoagulation; VKA, vitamin K antagonist. Open in new tab Table 3 Implantation technique and peri-implant management Position statement . Symbol . Evidence . A single dose of intravenous antibiotics should be administered before LCPM implantation, in accordance with ESC guidelines on cardiac pacing and cardiac re-synchronization therapy 17, 18, 20 Ultrasound-guided femoral vein puncture may be used to reduce the risk of vascular complications 14 Contrast injection via the delivery system may be used for confirmation of device position and wall contact EO Additional imaging manoeuvres (individualized X-ray angulations in more directions, right ventriculography) may be used to assess optimal target areas for device implantation and to avoid free-wall implantation EO For LCPM implantation in patients taking VKAs or DOACs, uninterrupted anticoagulation may be used 18, 19, 20, 21 A Heparin-bridging strategy in patients using OAC should not be used 17 Routine post-op antibiotic prophylaxis should not be used 17 Position statement . Symbol . Evidence . A single dose of intravenous antibiotics should be administered before LCPM implantation, in accordance with ESC guidelines on cardiac pacing and cardiac re-synchronization therapy 17, 18, 20 Ultrasound-guided femoral vein puncture may be used to reduce the risk of vascular complications 14 Contrast injection via the delivery system may be used for confirmation of device position and wall contact EO Additional imaging manoeuvres (individualized X-ray angulations in more directions, right ventriculography) may be used to assess optimal target areas for device implantation and to avoid free-wall implantation EO For LCPM implantation in patients taking VKAs or DOACs, uninterrupted anticoagulation may be used 18, 19, 20, 21 A Heparin-bridging strategy in patients using OAC should not be used 17 Routine post-op antibiotic prophylaxis should not be used 17 DOAC, direct oral anticoagulation; LCPM, leadless cardiac pacemaker; OAC, oral anticoagulation; VKA, vitamin K antagonist. Open in new tab Personnel and facility/equipment requirements Although LCPMs may be more resistant to infection,7,8,16 the 2021 ESC guidelines on cardiac pacing and cardiac re-synchronization therapy recommend strongly recommended to implant LCPMs under aseptic conditions in electrophysiologic laboratories or (hybrid) operating rooms17,18 equipped with high-resolution fluoroscopy to guide safe implantation and provide detailed assessment of the mechanical LCPM fixation. In a recent analysis, 78% of all 96 deaths associated with Micra implantations were preceded by cardiac tamponade, mostly within the first hour after implantation, and patients treated surgically were more likely to survive.19 Therefore, a written per-centre protocol on the management of a tamponade should be mandatory. Pericardiocentesis or surgical intervention should be urgently available for all implanting centres, with on-site surgery being the preferable option. As for TV-PM, a volume of 25 or more LCPM implantations per centre per year seems recommendable although definitive data are lacking.19–21 Operators should be trained in CIED implantations, and accustomed to femoral vein puncture and large-diameter sheaths, as well as manoeuvres in the RA and RV. Perioperative antibiotics and anticoagulants According to existing data on TV CIED implantations, routine intravenous administration of 2 g Cefazolin or Flucloxacillin or 1.5 g of Vancomycin in Penicillin-allergic patients within 60–120 min before, but not after implantation,17,18,20 is advisable. As about 75% of LCPM require oral anticoagulation (OAC) for stroke prevention, perioperative anticoagulation management is an important issue.3 The LCPM implantation is considered a minor bleeding risk procedure and can be performed at the minimal interruption interval of Direct OAC (being 12–24 h after last drug intake, or longer—depending on various parameters including renal function, age, size, and quality of the right ventricle), with a restart the same day >6 h after the procedure. In patients on vitamin K antagonists, implantation should be performed at an INR within a low therapeutic range at the physician’s discretion (Table 4).18–21 Table 4 Facility, equipment, and implanting staff requirements Position statement . Symbol . Evidence . LCPM should be implanted in an EP laboratory, OR, or hybrid-OR, with appropriate aseptic standards and a high-resolution X-ray options 17, 18 Implanting sites should have a written protocol and experience in the management of tamponade, with urgent access to cardiothoracic surgery EO LCPM should preferably be implanted by a cardiac electrophysiologist trained in CIED implantations EO LCPM implanters should be trained in femoral vascular access, operating large sheaths and manoeuvring in the right atrium and right ventricle EO Position statement . Symbol . Evidence . LCPM should be implanted in an EP laboratory, OR, or hybrid-OR, with appropriate aseptic standards and a high-resolution X-ray options 17, 18 Implanting sites should have a written protocol and experience in the management of tamponade, with urgent access to cardiothoracic surgery EO LCPM should preferably be implanted by a cardiac electrophysiologist trained in CIED implantations EO LCPM implanters should be trained in femoral vascular access, operating large sheaths and manoeuvring in the right atrium and right ventricle EO CIED, cardiac implantable electronic device; EP, electrophysiologic; LCPM, leadless cardiac pacemaker. Open in new tab Table 4 Facility, equipment, and implanting staff requirements Position statement . Symbol . Evidence . LCPM should be implanted in an EP laboratory, OR, or hybrid-OR, with appropriate aseptic standards and a high-resolution X-ray options 17, 18 Implanting sites should have a written protocol and experience in the management of tamponade, with urgent access to cardiothoracic surgery EO LCPM should preferably be implanted by a cardiac electrophysiologist trained in CIED implantations EO LCPM implanters should be trained in femoral vascular access, operating large sheaths and manoeuvring in the right atrium and right ventricle EO Position statement . Symbol . Evidence . LCPM should be implanted in an EP laboratory, OR, or hybrid-OR, with appropriate aseptic standards and a high-resolution X-ray options 17, 18 Implanting sites should have a written protocol and experience in the management of tamponade, with urgent access to cardiothoracic surgery EO LCPM should preferably be implanted by a cardiac electrophysiologist trained in CIED implantations EO LCPM implanters should be trained in femoral vascular access, operating large sheaths and manoeuvring in the right atrium and right ventricle EO CIED, cardiac implantable electronic device; EP, electrophysiologic; LCPM, leadless cardiac pacemaker. Open in new tab Magnetic resonance imaging scanning Micra (VR and AV) is CE approved for full-body 1.5 and 3T magnetic resonance imaging (MRI), Nanostim for full-body 1.5T MRI. The MRI was reported to cause heating of the LCPMs due to ‘antenna effect’; however, the increase in temperature was not clinically significant.22 The MRI scanning should be avoided within ≤6 weeks after implantation, or in case of elevated pacing threshold (>4.5 V at the nominal programmed pulse width).23 Both Micra and Nanostim need to be programmed to an MRI conditional mode prior to the scan. The patient’s ECG and peripheral pulse should be constantly monitored during MRI by experienced personnel, with an external defibrillator cardioverter with temporary pacing capabilities being immediately accessible. After the scan, the LCPMs should be interrogated and reprogrammed (Table 5). Table 5 MRI scanning in LCPM recipients Position statement . Symbol . Evidence . LCPMs need to be checked, programmed and reprogrammed before and directly after each MRI scan 23 For the Micra™, MRI scans should be avoided within 6 weeks after implantation or in case of elevated pacing thresholds (>4.5 V at 0.24 ms pulse width) 23 Position statement . Symbol . Evidence . LCPMs need to be checked, programmed and reprogrammed before and directly after each MRI scan 23 For the Micra™, MRI scans should be avoided within 6 weeks after implantation or in case of elevated pacing thresholds (>4.5 V at 0.24 ms pulse width) 23 LCPMs, leadless cardiac pacemakers; MRI, magnetic resonance imaging. Open in new tab Table 5 MRI scanning in LCPM recipients Position statement . Symbol . Evidence . LCPMs need to be checked, programmed and reprogrammed before and directly after each MRI scan 23 For the Micra™, MRI scans should be avoided within 6 weeks after implantation or in case of elevated pacing thresholds (>4.5 V at 0.24 ms pulse width) 23 Position statement . Symbol . Evidence . LCPMs need to be checked, programmed and reprogrammed before and directly after each MRI scan 23 For the Micra™, MRI scans should be avoided within 6 weeks after implantation or in case of elevated pacing thresholds (>4.5 V at 0.24 ms pulse width) 23 LCPMs, leadless cardiac pacemakers; MRI, magnetic resonance imaging. Open in new tab Emergent reprogramming and magnet effect Nanostim magnet mode can be programmed ON (VOO mode at 90 b.p.m.) or OFF; however, Micra will not be affected when a magnet is applied. Therefore, Micra needs to be programmed to an asynchronous mode (VOO) prior to procedures that carry a risk of electromagnetic interference, or staff must be prepared for temporary transcutaneous or endocardial pacing if reprogramming is unfeasible.23 However, a small series of six LCPM patients undergoing electrosurgery found no evidence of oversensing or device reset.24 Remote monitoring/care First-generation Nanostim LCPM did not have remote monitoring capabilities. Micra TPS can be connected to the CareLink System, which allows remote control of battery/device status, electrical parameters, rate histograms, device settings, and review electrograms. A mobile application (MyCareLink Heart mobile application for smartphone/tablet via Bluetooth) can also be used.25 End-of-service management The small size (battery life) and intracardiac placement (limited access) require consideration when prescribing LCPM. In 302 patients (age 73 ± 15 years) with Micra 7.6% discontinued LCPM at 3 years, due to cardiac resynchronization therapy (CRT) upgrade (45%), high threshold (25%), temporary usage (15%), battery depletion (10%), and PM syndrome (5%).26 The LCPM can be externally inactivated, and a new device implanted. Mechanical interference and tricuspid regurgitation are concerns with all abandoned devices,27 although co-implantation with other CIEDs (including simultaneous implantation and extraction) has been reported.13,15 Cremation of Micra LCPM seems to be safe (Table 6).28 Table 6 End-of-service and extraction of leadless devices Position statement . Symbol . Evidence . LCPM should be programmed off (000 mode) when no longer in service EO Co-implantation with other cardiac implantable electronic devices may be used when defibrillation (ICD) and/or re-synchronization therapy (CRT) are required 13, 15, 23 Extraction of leadless pacemaker is feasible if needed 29 Extraction should be performed by a trained team under appropriate conditions with urgent access to cardiothoracic surgery 29 Additional LPCM may be implanted in the right ventricle 15 Position statement . Symbol . Evidence . LCPM should be programmed off (000 mode) when no longer in service EO Co-implantation with other cardiac implantable electronic devices may be used when defibrillation (ICD) and/or re-synchronization therapy (CRT) are required 13, 15, 23 Extraction of leadless pacemaker is feasible if needed 29 Extraction should be performed by a trained team under appropriate conditions with urgent access to cardiothoracic surgery 29 Additional LPCM may be implanted in the right ventricle 15 ICD, implantable cardioverter defibrillator; LCPM, leadless cardiac pacemaker. Open in new tab Table 6 End-of-service and extraction of leadless devices Position statement . Symbol . Evidence . LCPM should be programmed off (000 mode) when no longer in service EO Co-implantation with other cardiac implantable electronic devices may be used when defibrillation (ICD) and/or re-synchronization therapy (CRT) are required 13, 15, 23 Extraction of leadless pacemaker is feasible if needed 29 Extraction should be performed by a trained team under appropriate conditions with urgent access to cardiothoracic surgery 29 Additional LPCM may be implanted in the right ventricle 15 Position statement . Symbol . Evidence . LCPM should be programmed off (000 mode) when no longer in service EO Co-implantation with other cardiac implantable electronic devices may be used when defibrillation (ICD) and/or re-synchronization therapy (CRT) are required 13, 15, 23 Extraction of leadless pacemaker is feasible if needed 29 Extraction should be performed by a trained team under appropriate conditions with urgent access to cardiothoracic surgery 29 Additional LPCM may be implanted in the right ventricle 15 ICD, implantable cardioverter defibrillator; LCPM, leadless cardiac pacemaker. Open in new tab Extraction of leadless pacemaker Extraction uses a designated retrieval sheath (Nanostim/Aveir) or counter traction (Micra). Successful extraction of 40 (100%) Micra and 73 cases (90%) of Nanostim devices were conducted at a mean of 46 and 256 days after implantation, respectively,29 and serious complications occurred in only 3%. These data suggest LCPM extraction in the first years after implantation is feasible and safe, provided it is performed by an adequately trained team with options for urgent access to cardiothoracic surgery. Programming options All LCPM can be programmed for rate-responsiveness by using special sensors. The Nanostim/Aveir LCPM uses central venous temperature for rate response.11 In Micra, accelerometer sensor counts exceeding set points initiate rate adaptation, and its response is automatically adjusted to a target rate histogram.30 Indeed, activity rate was proportional to workload (r = 0.86) with optimal adjustments in 83% of patients in a recent trial.31 In selected cases, vector changes and manual programming might be helpful. The new generation Micra AV enables VDD(R) mode by using the built-in-3-axis accelerometer to sense atrial contraction (A4).32 Mean A4 signal amplitude may vary and has been recorded lowest in the standing. Pre-implant echocardiographic evaluation of the atrial contractility may be useful in predicting adequate A4 sensing, but no definitive criteria or cutoffs exist at present. The Activity Mode Switch and VDD-VVI Mode Switch algorithms mitigate effects of A4 ventricular fusion at higher heart rate and mismatch between actual tracked rate and desired rate-response sensor rate, while the Rate Smoothing algorithm may overcome dropped beats due to A4 undersensing.33 To favour intrinsic AV conduction (saving battery life), the programmable AV Conduction Mode Switch algorithm periodically drops into VVI-40 (VVI + mode). If the intrinsic rate is >40, the device stays in the VVI+ mode, only to return to VDD mode when the rate is <40 b.p.m. However, it is advisable to inactivate this feature to maintain AV synchrony in the more appropriate VDD mode, rather than VVI 40 b.p.m. mode (Table 7).34 Table 7 AV synchronous leadless pacing Position statement . Symbol . Evidence . An LCPM with AV synchronous capability should be considered for all patients with sinus rhythm that may benefit from AV synchrony EO Position statement . Symbol . Evidence . An LCPM with AV synchronous capability should be considered for all patients with sinus rhythm that may benefit from AV synchrony EO LCPM, leadless cardiac pacemaker. Open in new tab Table 7 AV synchronous leadless pacing Position statement . Symbol . Evidence . An LCPM with AV synchronous capability should be considered for all patients with sinus rhythm that may benefit from AV synchrony EO Position statement . Symbol . Evidence . An LCPM with AV synchronous capability should be considered for all patients with sinus rhythm that may benefit from AV synchrony EO LCPM, leadless cardiac pacemaker. Open in new tab Patient selection: LCPM In the recently published 2021 ESC guidelines18 for pacing and CRT, LCPM should be considered in patients without upper extremity venous access or a high risk of device infection (e.g. previous CIED infection and patients on haemodialysis; Class IIa/B).23 The LCPM should also be considered as an alternative to standard single-lead TV-PM, taking into consideration life expectancy and using shared decision-making (Class IIb/B).18,23 Atrial or dual chamber TV-PM should be preferred in patients with (advanced or symptomatic) sick sinus syndrome to avoid atrial fibrillation (AF) progression and stroke, and PM syndrome.35–37 The TV-PM and/or epicardial biventricular or conduction system pacing should be preferred in patients with a pacing indication and anticipated high ventricular pacing rate (>20%), heart failure, and impaired left ventricular function [left ventricular ejection fraction (LVEF) ≤35%] that do not wish to receive an ICD.18 Patients with permanent AF and AV block or slow ventricular rate are optimal candidates for VVI LCPM.18 The AV synchronous (VDD) pacing has become an option by accelerometer-based sensing of the atrial contraction,33–35 but this requires precise programming while maximal tracking does not exceed 110 b.p.m. This option may be considered in selected patients with sufficient sinus rhythm, but with transient (or permanent) AV block if a TV system is not considered appropriate. The same may apply to patients with transient sinus arrest or AV block and a low anticipated ventricular pacing rate (≤5% of beats). The LCPM or TV systems may equally be considered in inactive patients in sinus rhythm, since single-chamber pacing does not increase mortality or cause symptoms in this subgroup of patients.35,36 The decision to implant a TV-PM or LCPM should always weigh potential benefits and risks.23 Patients with two or more risk factors for infection (i.e. diabetes mellitus, renal dysfunction, chronic use of corticosteroids, history of recurrent infections, and immunosuppressive therapy) may benefit from the low risk for infection.9,37 The LCPM implantation is contraindicated in the presence of a mechanical tricuspid valve, to avoid risks of AV block, entrapment of the delivery system and/or device itself. In contrast, an LCPM system may be preferred in case of dysfunctional or reconstructed tricuspid valves or after biological tricuspid valve replacement, to avoid (aggravation of) valve regurgitation and endocarditis. When considering implanting an LCPM, physicians must also weigh the advantages of avoiding TV leads and a device in subcutaneous pocket, against the disadvantages of the LCPM finite battery life and the remote retrieval position in the heart. Younger patients could benefit from avoiding TV leads when a long lifespan is expected, but the device does not perform physiologic pacing and the RV cannot sustain too many LCPM in the RV position. Extraction might become necessary at some point in time or hybrid TV and LCPM strategies may be offered. A shared decision-making process seems warranted, to inform patients about the differences between these devices, both medically as well as from a practical point of view. In the absence of long-term consequences, LCPM implantation in the young below 20 years of age does not seem advisable aside from specific medical circumstances that preclude TV-PM. Given a life expectancy of 80 years of the general population and an estimated LCPM durability of about 10 years, a general rule of thumb should be that conventional TV-PM should be preferred in patients <60 years of age. Cosmetic or lifestyle choices should not be considered compelling reasons for an LCPM, although patients with compelling professional (work-related) and/or avocational activities may benefit from a lower complication rate of LCPM (Table 8).5 Table 8 LCPM position statements based on the underlying arrhythmia and clinical circumstances based on expert opinion Pacing indication clinical condition . Transient SA or AVB with need of backup pacing and low anticipated ventricular pacing burden . Recurrent cardioinhibitory syncope and low anticipated ventricular pacing burdena . SR with complete AVB with no need for a high tracking rate . Permanent AF and AVB/slow ventricular response with increased anticipated ventricular pacing rate . SR and AVB with increased anticipated ventricular pacing burdenb . SSS with increased anticipated ventricular pacing burdenb . Missing or difficult superior venous access (V. subclavia, V. cava sup., congenital heart disease) History or elevated risk of CIED infection (diabetes mellitus, dialysis, chronic use of corticosteroids, history of recurrent infections, and immunosuppressive therapy, frailty) Tricuspid valve dysfunction risk (bio-valve replacement or repair) Mechanical tricuspid valve Heart failure and moderate to severe LV dysfunction (LVEF ≤35%) refusing ICD therapy Age <65 years including young patients <20 years of age Professional/avocational reasons Pacing indication clinical condition . Transient SA or AVB with need of backup pacing and low anticipated ventricular pacing burden . Recurrent cardioinhibitory syncope and low anticipated ventricular pacing burdena . SR with complete AVB with no need for a high tracking rate . Permanent AF and AVB/slow ventricular response with increased anticipated ventricular pacing rate . SR and AVB with increased anticipated ventricular pacing burdenb . SSS with increased anticipated ventricular pacing burdenb . Missing or difficult superior venous access (V. subclavia, V. cava sup., congenital heart disease) History or elevated risk of CIED infection (diabetes mellitus, dialysis, chronic use of corticosteroids, history of recurrent infections, and immunosuppressive therapy, frailty) Tricuspid valve dysfunction risk (bio-valve replacement or repair) Mechanical tricuspid valve Heart failure and moderate to severe LV dysfunction (LVEF ≤35%) refusing ICD therapy Age <65 years including young patients <20 years of age Professional/avocational reasons AF, atrial fibrillation; AVB, atrioventricular block; CIED, cardiac implantable electronic device; SA, sinus arrest; SR, sinus rhythm; SSS, sick sinus syndrome. a ≤20% of beats.18 b >20% of beats.18 Open in new tab Table 8 LCPM position statements based on the underlying arrhythmia and clinical circumstances based on expert opinion Pacing indication clinical condition . Transient SA or AVB with need of backup pacing and low anticipated ventricular pacing burden . Recurrent cardioinhibitory syncope and low anticipated ventricular pacing burdena . SR with complete AVB with no need for a high tracking rate . Permanent AF and AVB/slow ventricular response with increased anticipated ventricular pacing rate . SR and AVB with increased anticipated ventricular pacing burdenb . SSS with increased anticipated ventricular pacing burdenb . Missing or difficult superior venous access (V. subclavia, V. cava sup., congenital heart disease) History or elevated risk of CIED infection (diabetes mellitus, dialysis, chronic use of corticosteroids, history of recurrent infections, and immunosuppressive therapy, frailty) Tricuspid valve dysfunction risk (bio-valve replacement or repair) Mechanical tricuspid valve Heart failure and moderate to severe LV dysfunction (LVEF ≤35%) refusing ICD therapy Age <65 years including young patients <20 years of age Professional/avocational reasons Pacing indication clinical condition . Transient SA or AVB with need of backup pacing and low anticipated ventricular pacing burden . Recurrent cardioinhibitory syncope and low anticipated ventricular pacing burdena . SR with complete AVB with no need for a high tracking rate . Permanent AF and AVB/slow ventricular response with increased anticipated ventricular pacing rate . SR and AVB with increased anticipated ventricular pacing burdenb . SSS with increased anticipated ventricular pacing burdenb . Missing or difficult superior venous access (V. subclavia, V. cava sup., congenital heart disease) History or elevated risk of CIED infection (diabetes mellitus, dialysis, chronic use of corticosteroids, history of recurrent infections, and immunosuppressive therapy, frailty) Tricuspid valve dysfunction risk (bio-valve replacement or repair) Mechanical tricuspid valve Heart failure and moderate to severe LV dysfunction (LVEF ≤35%) refusing ICD therapy Age <65 years including young patients <20 years of age Professional/avocational reasons AF, atrial fibrillation; AVB, atrioventricular block; CIED, cardiac implantable electronic device; SA, sinus arrest; SR, sinus rhythm; SSS, sick sinus syndrome. a ≤20% of beats.18 b >20% of beats.18 Open in new tab Wireless left ventricular endocardial left ventricular pacing (WiSE-CRT system) Background Endocardial LV pacing may offer benefits over traditional cardiac re-synchronization.38 The WiSE-CRT system (EBR systems, Sunnyvale, CA, USA) is a CE approved system that is not widely available or reimbursed at this time. The system allows delivery of leadless LV endocardial pacing. Figure 3 demonstrates the components of the WiSE-CRT system, consisting of a transmitter implanted over the intercostal muscle in a pre-identified intercostal space and connected to a generator which is placed in the adjacent mid-axillary line. The wireless endocardial electrode is implanted in the LV endocardium. The WiSE system requires sensing of a pacing signal from an existing pacing system (co-implant) to trigger delivery of a beam of ultrasound energy by the transmitter focused to the endocardial electrode, that converts this into electrical energy to pace the LV myocardium and achieving essentially simultaneous biventricular pacing. Figure 3 Open in new tabDownload slide WiSE-CRT system (reproduced with permission from EBR Systems). RV, right ventricle. Implant technique The battery/transmitter and endocardial electrode can be implanted in two stages or as a single-stage procedure. The procedure is usually performed under general anaesthesia as the transmitter requires surgical placement in a pre-identified intercostal space after ultrasound screening has been performed to ensure a satisfactory acoustic window. The endocardial electrode can be introduced via a retrograde transaortic approach which requires large bore femoral arterial access (12Fr). An alternative technique has been developed where the electrode is delivered via a transseptal approach. This requires full heparinization with an activated clotting time >300 s. The electrode is delivered to the LV endocardium at a site with satisfactory electrical parameters and then is embedded into the LV endocardium and released. Following implant, the electrode becomes fully endothelialized after several weeks and dual antiplatelet therapy is considered sufficient. The WiSE-CRT feasibility was initially described in 17 patients who were either CRT non-responders, or who were at high risk, needed device upgrade, or had prior failed CRT upgrade.39 The trial was terminated early due to procedure-related pericardial effusions that resulted in re-design of the delivery sheath to incorporate a balloon at the distal tip to reduce trauma to the LV wall. The SELECT-LV trial40 subsequently reported outcomes in 35 patients with high procedural success (97.1%), with 33 patients meeting the primary endpoint of successful biventricular pacing at 1 month. At 6 months, 66% patients showed favourable echocardiographic response and 84.8% had an improvement in clinical composite score. There were no periprocedural pericardial effusions; however, complication rate was 8.6% at 24 h and 22.9% at 1 month, with one procedure-related death due to fatal ventricular arrhythmia (VA) during implantation, one embolization of the endocardial electrode, and one femoral artery fistula requiring surgical intervention. The largest report of WiSE-CRT implantation to date is a multicentre registry41 including 90 patients from 14 European sites that reported a high procedural success and chronic delivery of biventricular pacing in 94.4% of patients with 69.8% of patients reporting improved 6-month clinical composite score. Reported rates of acute (<24 h), intermediate (24 h to 1 month), and chronic (1–6 months) complications were 4.4, 18.8, and 6.7%, respectively, including three procedural or device-related deaths, two of which were secondary to LV perforation. Only one stroke was reported in the follow-up period, which was not felt to be device-related. SOLVE-CRT is an international, randomized trial of the WiSE-CRT system that is currently enrolling in Europe and North America.42 The study initially aimed to recruit 350 patients who would all undergo implant and then be randomized 1:1 to the device turned ON or OFF, with follow-up at 6 months. However, due to the COVID-19 pandemic the FDA approved a modified protocol, with all patients being recruited to a single-arm treatment-only phase, and excluding non-responders.43 Current implant criteria for WiSE-CRT are shown in Table 9. Table 9 WiSE-CRT implant criteria CRT indication . Clinical situation . (a) Class I: NYHA II–V, EF ≤35%, LBBB, QRS≥150 ms 1. ‘Non-responder’: Functional CRT system and despite guideline directed medical therapy/optimal programming not responded for minimum 6 months. Non-response defined as remaining clinically unchanged or worsened: EF unchanged or worsened and clinical status unchanged or worsened (b) Class IIa (1): NYHA II–IV, EF ≤35%, LBBB, QRS ≥ 130 < 150 ms 2. ‘Previously Untreatable’: Pts full or partial CRT system, with (i) failed CS lead implant, (ii) Implanted CS lead but programmed off, or (iii) high risk upgrades with relative contraindication to CS lead implant (c) Class IIa (2): NYHA II–IV, EF ≤35%, non-LBBB, QRS ≥150 ms CRT indication . Clinical situation . (a) Class I: NYHA II–V, EF ≤35%, LBBB, QRS≥150 ms 1. ‘Non-responder’: Functional CRT system and despite guideline directed medical therapy/optimal programming not responded for minimum 6 months. Non-response defined as remaining clinically unchanged or worsened: EF unchanged or worsened and clinical status unchanged or worsened (b) Class IIa (1): NYHA II–IV, EF ≤35%, LBBB, QRS ≥ 130 < 150 ms 2. ‘Previously Untreatable’: Pts full or partial CRT system, with (i) failed CS lead implant, (ii) Implanted CS lead but programmed off, or (iii) high risk upgrades with relative contraindication to CS lead implant (c) Class IIa (2): NYHA II–IV, EF ≤35%, non-LBBB, QRS ≥150 ms CRT indications are adopted from the ESC guidelines on cardiac pacing and CRT.18 LVEF, left ventricular ejection fraction; NYHA, New York Heart Association. Open in new tab Table 9 WiSE-CRT implant criteria CRT indication . Clinical situation . (a) Class I: NYHA II–V, EF ≤35%, LBBB, QRS≥150 ms 1. ‘Non-responder’: Functional CRT system and despite guideline directed medical therapy/optimal programming not responded for minimum 6 months. Non-response defined as remaining clinically unchanged or worsened: EF unchanged or worsened and clinical status unchanged or worsened (b) Class IIa (1): NYHA II–IV, EF ≤35%, LBBB, QRS ≥ 130 < 150 ms 2. ‘Previously Untreatable’: Pts full or partial CRT system, with (i) failed CS lead implant, (ii) Implanted CS lead but programmed off, or (iii) high risk upgrades with relative contraindication to CS lead implant (c) Class IIa (2): NYHA II–IV, EF ≤35%, non-LBBB, QRS ≥150 ms CRT indication . Clinical situation . (a) Class I: NYHA II–V, EF ≤35%, LBBB, QRS≥150 ms 1. ‘Non-responder’: Functional CRT system and despite guideline directed medical therapy/optimal programming not responded for minimum 6 months. Non-response defined as remaining clinically unchanged or worsened: EF unchanged or worsened and clinical status unchanged or worsened (b) Class IIa (1): NYHA II–IV, EF ≤35%, LBBB, QRS ≥ 130 < 150 ms 2. ‘Previously Untreatable’: Pts full or partial CRT system, with (i) failed CS lead implant, (ii) Implanted CS lead but programmed off, or (iii) high risk upgrades with relative contraindication to CS lead implant (c) Class IIa (2): NYHA II–IV, EF ≤35%, non-LBBB, QRS ≥150 ms CRT indications are adopted from the ESC guidelines on cardiac pacing and CRT.18 LVEF, left ventricular ejection fraction; NYHA, New York Heart Association. Open in new tab Future perspectives on pacing without a lead in the heart Completely leadless CRT can be achieved with the WiSE-CRT system if used in combination with an LCPM, with feasibility demonstrated in a small multicentre series of 8 patients with a Micra™ (Medtronic) as co-implant.44 Similarly, incorporation of a subcutaneous ICD allows a completely leadless CRT defibrillation system.45 Entirely leadless pacing systems may represent an attractive option in the future for patients with vascular access issues and recurrent lead complications. Conduction system pacing may also be feasible in the future if the endocardial electrode can be targeted and deployed to the left bundle branch area, although this may require further refinement of the implantation tools and technique. Leadless LV endocardial pacing with the WiSE-CRT system may offer advantages over conventional CRT with a greater choice of pacing sites. The endocardial electrode becomes fully endothelialized, which may reduce thromboembolic complications, negating the need for long-term anticoagulation and reducing risks associated with extraction of lead-based systems. Subcutaneous extravascular implantable cardioverter defibrillators Background subcutaneous implantable cardioverter defibrillator Transvenous leads may be associated with complications at implant and during the lifecycle of the ICD, including pneumothorax, perforation, infection, dysfunction, and obstruction, as well as extraction related issues. In 2009, an entirely subcutaneous ICD (S-ICD) became available to overcome such issues. The 9-F subcutaneous lead has an 8 cm long coil for defibrillation, with proximal and distal electrodes for sensing and post-shock pacing, and is typically positioned parallel to the left sternal border, while the device sits on the left posterolateral thorax. Defibrillation (maximum output 80J) has proved effective during more than a decade of clinical experience. The device only offers limited transthoracic post-shock ventricular pacing, excluding its use for those that require bradycardia pacing, antitachycardia pacing, or re-synchronization therapy. Overview of studies on subcutaneous implantable cardioverter defibrillator In 2010, Bardy et al.46 described the pilot phase of the device and lead design, demonstrating that a parasternal lead and the generator in a left posterolateral position (Figure 4) delivered optimal chronic defibrillation performance, and the system was granted CE approval. Since the device is not endovascular, defibrillation thresholds (DFTs) were significantly higher compared with TV-ICDs. The subsequent IDE trial47 enabling FDA approval showed 180 days freedom of device-related complication in 99%, with 100% successful conversion of 304 evaluable induced and 112 spontaneous VA events, with a 13.1% inappropriate shock (IAS) rate after close to 1-year follow-up. Figure 4 Open in new tabDownload slide Frontal and lateral image of an implanted S-ICD with a parasternal shock lead and left posterolateral generator position. Several studies and registries have been published in various clinical conditions and patient populations (Table 10). The EFFORTLESS observational registry48 included nearly 1000 patients implanted with first-generation devices and lead. The S-ICD PASS trial49 studied the post-FDA-approval marketing experience in the USA, including the original and second-generation devices and leads. The PRAETORIAN trial48 randomized patients to a single-chamber TV-ICD or the S-ICD, again with mostly first- and second-generation devices and leads: median follow-up was 4 years with a combined primary endpoint of adverse events and IAS. The more recent prospective multicentre UNTOUCHED trial,50 included patients with a primary prevention indication due to LVEF of ≤35% and focused on IAS rate with the latest S-ICD model including the high-pass filter (SMART Pass). Table 10 Details about trials with the S-ICD Variable . EFFORTLESS45 (n = 985) . IDE44 (n = 321) . PRAETORIAN45 (n = 426) . PAS47 (n = 1637) . UNTOUCHED48 (n = 1116) . Enrol start date 10-2010 01-2010 03-2011 03-2013 06-2015 Follow-up 73 months 11 months 48 months 12 months 18 months Age (years) 48 ± 17 52 ± 16 63 (54–69) 53 ± 15 56 ± 12 Male gender 72.0% 74.1% 79.1% 68.6% 74.4% LVEF (%) 43 ± 18 36 ± 16 30 (25–35) 32 ± 15 26 ± 6 Ischaemic heart disease 28.6% NR 67.8% 33.2% 41.2% Atrial fibrillation 15.9% 15.3% 27.0% 16.2% 12.7% Primary prevention 64.9% 79.4% 81.2% 76.7% 100% Variable . EFFORTLESS45 (n = 985) . IDE44 (n = 321) . PRAETORIAN45 (n = 426) . PAS47 (n = 1637) . UNTOUCHED48 (n = 1116) . Enrol start date 10-2010 01-2010 03-2011 03-2013 06-2015 Follow-up 73 months 11 months 48 months 12 months 18 months Age (years) 48 ± 17 52 ± 16 63 (54–69) 53 ± 15 56 ± 12 Male gender 72.0% 74.1% 79.1% 68.6% 74.4% LVEF (%) 43 ± 18 36 ± 16 30 (25–35) 32 ± 15 26 ± 6 Ischaemic heart disease 28.6% NR 67.8% 33.2% 41.2% Atrial fibrillation 15.9% 15.3% 27.0% 16.2% 12.7% Primary prevention 64.9% 79.4% 81.2% 76.7% 100% IDE, investigational device exemption; LVEF, left ventricular ejection fraction. Open in new tab Table 10 Details about trials with the S-ICD Variable . EFFORTLESS45 (n = 985) . IDE44 (n = 321) . PRAETORIAN45 (n = 426) . PAS47 (n = 1637) . UNTOUCHED48 (n = 1116) . Enrol start date 10-2010 01-2010 03-2011 03-2013 06-2015 Follow-up 73 months 11 months 48 months 12 months 18 months Age (years) 48 ± 17 52 ± 16 63 (54–69) 53 ± 15 56 ± 12 Male gender 72.0% 74.1% 79.1% 68.6% 74.4% LVEF (%) 43 ± 18 36 ± 16 30 (25–35) 32 ± 15 26 ± 6 Ischaemic heart disease 28.6% NR 67.8% 33.2% 41.2% Atrial fibrillation 15.9% 15.3% 27.0% 16.2% 12.7% Primary prevention 64.9% 79.4% 81.2% 76.7% 100% Variable . EFFORTLESS45 (n = 985) . IDE44 (n = 321) . PRAETORIAN45 (n = 426) . PAS47 (n = 1637) . UNTOUCHED48 (n = 1116) . Enrol start date 10-2010 01-2010 03-2011 03-2013 06-2015 Follow-up 73 months 11 months 48 months 12 months 18 months Age (years) 48 ± 17 52 ± 16 63 (54–69) 53 ± 15 56 ± 12 Male gender 72.0% 74.1% 79.1% 68.6% 74.4% LVEF (%) 43 ± 18 36 ± 16 30 (25–35) 32 ± 15 26 ± 6 Ischaemic heart disease 28.6% NR 67.8% 33.2% 41.2% Atrial fibrillation 15.9% 15.3% 27.0% 16.2% 12.7% Primary prevention 64.9% 79.4% 81.2% 76.7% 100% IDE, investigational device exemption; LVEF, left ventricular ejection fraction. Open in new tab All these studies43–50 showed consistent 94.0–98.6% freedom from device-related complications, with infection rates declining from 2.5 to <1.0% by avoiding a third incision (see below) and improving implant technique. Although recently lead fractures have become apparent for the re-designed third generation SQ leads, dysfunction of earlier leads has been rarely observed. In the studies, the conversion rate of induced VA at implant as well as spontaneous VA during follow-up is 97% or higher. Although limited pacing options may be a barrier for S-ICD adoption, careful patient selection has kept the need for conversion to TV or cardiac re-synchronization ICD devices as low as 1–2%. Implementing dual zone programming and higher rate cutoffs for the conditional shock zone (200–250/min) and the shock zone to (>250 b.p.m.), resulted in 70 and 56% relative risk reduction in IAS for supraventricular tachycardia (SVT) and oversensing, respectively. The EFFORTLESS showed 8.1% IAS rate at 1 year, mainly due to T-wave oversensing; this was reduced to 6.8% in S-ICD PAS, 4.8% in PRAETORIAN, and 2.9% in UNTOUCHED in patients with the latest S-ICD model and activated SMART Pass filter that reduces T-wave oversensing. As a result, SVT is now the main cause of IAS, as with TV-ICDs. The randomised PRAETORIAN trial found no difference in first shock efficacy between the S-ICD (93.8%) and TV-ICD (91.6%; P = 0.40), and no difference in primary endpoint, with less device-related complications [hazard ratio (HR) 0.69] but more IASs (HR 1.43) for the S-ICD. In PRAETORIAN, more than 78% of the S-ICD devices did not have SMART Pass available. As a result, several S-ICD patients were shocked for slow VTs that might have responded to ATP; conversely, several TV-ICD patients received inappropriate or unsuccessful ATP. Long-term follow-up at 5 years in EFFORTLESS51 showed that first and final shock efficacy for discrete VAs was consistent at 90 and 98%, respectively, with storm episode final shock efficacy at 95.2%. Time to therapy remains around 15 s. Overall 1- and 5-year complication rates were 8.9 and 15.2%, respectively. There were no structural lead failures. The IASrates at 1 and 5 years were 8.7 and 16.9%, respectively (Table 10). Implantation of the subcutaneous implantable cardioverter defibrillator Preparation and anaesthesia The S-ICD implantation may be performed with intravenous antibiotic protection under local anaesthesia with conscious sedation or under general anaesthesia, although there is no association with better outcomes.50 Recently (ultrasound-guided) regional nerve block in addition to local anaesthesia has shown good outcomes for acute and post-procedural pain alleviation.52 Careful preparation prior to S-ICD implantation is important, as the locations of device and lead are critical to both detection and defibrillation efficacy. Physical landmarks and fluoroscopy guide optimal positioning of the incisions at the xiphoid junction and anterior axillary line, placement of the lead body parallel to the sternum, and of the generator at the left posterolateral thorax. Identification of landmarks with a marker pen is recommended to guide physicians during the first implants in their learning curve.53–56 Surgical technique Early implants used a three-incision technique (one lateral pocket incision and one at each end of the parasternal lead tunnel). However, a two-incision technique (omitting the superior parasternal incision) shortens procedure time with a superior cosmetic result while not affecting S-ICD efficacy or safety.57 A low DFT requires positioning of the generator at the level of the apex, and posterior to the mid-axillary line, with no adipose tissue deep to the generator and coil. A generator pocket between the serratus anterior and the latissimus dorsi muscles improves comfort and may reduce complications such as infection and erosion. A combination of the two-incision technique and intermuscular generator pocket is now standard for S-ICD implantation.58 Massage and saline irrigation of the lead tunnel and (prior to closure) of the pocket reduces the risk of signal artefacts and ineffective defibrillation due to air. Careful attention should be taken when connecting the lead in the header to ensure the electrode pin is in the most distal position to eliminate signal artefacts. Defibrillation testing In the S-ICD validation phase,43–47 defibrillation testing with two successful conversions of induced VA at 65J (i.e. a 15J safety margin) was mandatory. Although it is still recommended in guidelines,59–61 many operators have stopped testing because of high published efficacy (>90%) at 65J43–47 and recent data suggesting no difference in first shock efficacy for spontaneous VA in patients that did not undergo testing at implant.62 Recently, the PRAETORIAN score (Figure 5) was proposed as a means of predicting defibrillation testing outcome63 by reviewing post-implant X-rays and awarding cumulative points for the amount of fat between the shock coil and the sternum, anterior generator position, and amount of tissue under the generator. A score <90 is associated with >99% likelihood of a successful VA conversion, while a score >150 has been associated with a >50% risk of failure. This scoring system is to be validated in the ongoing prospective PRAETORIAN-DFT trial. Optimal implant conditions at baseline also correlate with maintained defibrillation testing success, which may guide the need for testing at generator exchange.64 Figure 5 Open in new tabDownload slide The PRAETORIAN score may predict successful deibrillation testing by the S-ICD.63 S-ICD, subcutaneous implantable cardioverter defibrillator. Patient selection subcutaneous implantable cardioverter defibrillator The S-ICD therapy considerations and recommendations are available in international guidelines although its position is still very moderate in the latest 2015 ESC guidelines59 and HRS guidelines for sudden cardiac death prevention,60,61 with a Class IIa recommendation as alternative to TV-ICD when no pacing is needed. In specific circumstances such as infection risk or difficult venous access the S-ICD is Class I option in the HRS guidelines but a IIb bail-out option in the ESC guidelines (expert opinion). Given that the S-ICD only offers post-shock pacing, any patient requiring bradycardia pacing, antitachycardia pacing, or cardiac re-synchronization is not indicated for an S-ICD. Furthermore, pre-procedural surface ECG screening is a key to proper VA detection and discrimination to ensure appropriate therapy when needed and minimize the risk of IASs. This has evolved from manual to automated screening incorporated in the S-ICD programmer (Figure 5). Although only a single vector is required to pass screening in the supine and standing position, it is advisable to test both the left and right side of the sternum for alternative options. Previous studies have reported a 7–8% screening failure, and up to 16% in specific conditions such as hypertrophic cardiomyopathy.54 In these conditions, it is prudent to screen patients during exercise as significant dynamic changes in QRS (rate dependent bundle branch block) and T-wave morphology may occur. Resulting oversensing may be mitigated by ensuring a maximum number of vectors is available during post-implant troubleshooting.56 In cases with only one suitable vector or low R:T ratio (some cardiomyopathies and channelopathies), exercise screening for oversensing should be performed post-implantation to select the best vector and template (Table 11, Figure 6). Figure 6 Open in new tabDownload slide Three vector options are possible between electrodes and can of the S-ICD. The S-ICD programmer provides automatic screening of the cardiac signal to determine appropriate vector detection even before implantation. S-ICD, subcutaneous implantable cardioverter defibrillator. Table 11 Position statements non-transvenous ICD Position statements: general patient selection . Symbol . Evidence . Transvenous ICDs should be considered in all patients with a guideline indication for sudden cardiac death prevention 61–63 Non-transvenous ICDs should be considered as an alternative in all patients that do not require active pacing for bradycardia, re-synchronization, or antitachycardia pacing 61–63 Non-transvenous ICD should be considered in patients in whom alternatives to a transvenous approach are required (vascular abnormalities, recent infection, haemodialysis, young age) 61–63 Position statements: S-ICD implantation S-ICD implantation can be performed under general and monitored anaesthesia or conscious sedation with adequate pain alleviation 52 A single dose of intravenous antibiotics is recommended before S-ICD implantation 17, 18, 20, 61–63 Pre-implant marking of the desired incisions and position of the components of the S-ICD with anatomical landmarks and/or fluoroscopy should be used to facilitate an optimal implant result 55, 57 Ultrasound-guided regional nerve blocking may be used in addition to local anaesthesia 56 A two-incision technique should be used in all patients 59, 60 A three-incision technique may be used to ensure lead stability and contact with the sternum in selected patients with high BMI 65 Air should be excluded from the lateral pocket, parasternal incision, and tunnelled lead trajectory to prevent sensing problems and ineffective shocks during implant EO Position statements: S-ICD testing Defibrillation testing should be considered during the first S-ICD implantation with a safety margin of 15J 47–52, 64 Defibrillation testing may be performed during S-ICD replacement with a safety margin of 15J EO When a left parasternal lead position does not yield successful defibrillation a right parasternal lead position may provide an alternative EO When defibrillation testing is judged unsafe on clinical grounds a low PRAETORIAN score (<90) may be an acceptable surrogate for successful conversion 65 For primary prevention implants, dual zone programming is advisable with a conditional zone starting at 200 b.p.m. and shock zone starting at 250 b.p.m. with 80J output 51,52 A TV-PM or LCPM may be added to a non-TV-ICD in patients that develop a need for pacing EO Position statements: general patient selection . Symbol . Evidence . Transvenous ICDs should be considered in all patients with a guideline indication for sudden cardiac death prevention 61–63 Non-transvenous ICDs should be considered as an alternative in all patients that do not require active pacing for bradycardia, re-synchronization, or antitachycardia pacing 61–63 Non-transvenous ICD should be considered in patients in whom alternatives to a transvenous approach are required (vascular abnormalities, recent infection, haemodialysis, young age) 61–63 Position statements: S-ICD implantation S-ICD implantation can be performed under general and monitored anaesthesia or conscious sedation with adequate pain alleviation 52 A single dose of intravenous antibiotics is recommended before S-ICD implantation 17, 18, 20, 61–63 Pre-implant marking of the desired incisions and position of the components of the S-ICD with anatomical landmarks and/or fluoroscopy should be used to facilitate an optimal implant result 55, 57 Ultrasound-guided regional nerve blocking may be used in addition to local anaesthesia 56 A two-incision technique should be used in all patients 59, 60 A three-incision technique may be used to ensure lead stability and contact with the sternum in selected patients with high BMI 65 Air should be excluded from the lateral pocket, parasternal incision, and tunnelled lead trajectory to prevent sensing problems and ineffective shocks during implant EO Position statements: S-ICD testing Defibrillation testing should be considered during the first S-ICD implantation with a safety margin of 15J 47–52, 64 Defibrillation testing may be performed during S-ICD replacement with a safety margin of 15J EO When a left parasternal lead position does not yield successful defibrillation a right parasternal lead position may provide an alternative EO When defibrillation testing is judged unsafe on clinical grounds a low PRAETORIAN score (<90) may be an acceptable surrogate for successful conversion 65 For primary prevention implants, dual zone programming is advisable with a conditional zone starting at 200 b.p.m. and shock zone starting at 250 b.p.m. with 80J output 51,52 A TV-PM or LCPM may be added to a non-TV-ICD in patients that develop a need for pacing EO BMI, body mass index; LCPM, leadless cardiac pacemaker; PM, pacemaker; S-ICD, subcutaneous implantable cardioverter defibrillator; TV, transvenous. Open in new tab Table 11 Position statements non-transvenous ICD Position statements: general patient selection . Symbol . Evidence . Transvenous ICDs should be considered in all patients with a guideline indication for sudden cardiac death prevention 61–63 Non-transvenous ICDs should be considered as an alternative in all patients that do not require active pacing for bradycardia, re-synchronization, or antitachycardia pacing 61–63 Non-transvenous ICD should be considered in patients in whom alternatives to a transvenous approach are required (vascular abnormalities, recent infection, haemodialysis, young age) 61–63 Position statements: S-ICD implantation S-ICD implantation can be performed under general and monitored anaesthesia or conscious sedation with adequate pain alleviation 52 A single dose of intravenous antibiotics is recommended before S-ICD implantation 17, 18, 20, 61–63 Pre-implant marking of the desired incisions and position of the components of the S-ICD with anatomical landmarks and/or fluoroscopy should be used to facilitate an optimal implant result 55, 57 Ultrasound-guided regional nerve blocking may be used in addition to local anaesthesia 56 A two-incision technique should be used in all patients 59, 60 A three-incision technique may be used to ensure lead stability and contact with the sternum in selected patients with high BMI 65 Air should be excluded from the lateral pocket, parasternal incision, and tunnelled lead trajectory to prevent sensing problems and ineffective shocks during implant EO Position statements: S-ICD testing Defibrillation testing should be considered during the first S-ICD implantation with a safety margin of 15J 47–52, 64 Defibrillation testing may be performed during S-ICD replacement with a safety margin of 15J EO When a left parasternal lead position does not yield successful defibrillation a right parasternal lead position may provide an alternative EO When defibrillation testing is judged unsafe on clinical grounds a low PRAETORIAN score (<90) may be an acceptable surrogate for successful conversion 65 For primary prevention implants, dual zone programming is advisable with a conditional zone starting at 200 b.p.m. and shock zone starting at 250 b.p.m. with 80J output 51,52 A TV-PM or LCPM may be added to a non-TV-ICD in patients that develop a need for pacing EO Position statements: general patient selection . Symbol . Evidence . Transvenous ICDs should be considered in all patients with a guideline indication for sudden cardiac death prevention 61–63 Non-transvenous ICDs should be considered as an alternative in all patients that do not require active pacing for bradycardia, re-synchronization, or antitachycardia pacing 61–63 Non-transvenous ICD should be considered in patients in whom alternatives to a transvenous approach are required (vascular abnormalities, recent infection, haemodialysis, young age) 61–63 Position statements: S-ICD implantation S-ICD implantation can be performed under general and monitored anaesthesia or conscious sedation with adequate pain alleviation 52 A single dose of intravenous antibiotics is recommended before S-ICD implantation 17, 18, 20, 61–63 Pre-implant marking of the desired incisions and position of the components of the S-ICD with anatomical landmarks and/or fluoroscopy should be used to facilitate an optimal implant result 55, 57 Ultrasound-guided regional nerve blocking may be used in addition to local anaesthesia 56 A two-incision technique should be used in all patients 59, 60 A three-incision technique may be used to ensure lead stability and contact with the sternum in selected patients with high BMI 65 Air should be excluded from the lateral pocket, parasternal incision, and tunnelled lead trajectory to prevent sensing problems and ineffective shocks during implant EO Position statements: S-ICD testing Defibrillation testing should be considered during the first S-ICD implantation with a safety margin of 15J 47–52, 64 Defibrillation testing may be performed during S-ICD replacement with a safety margin of 15J EO When a left parasternal lead position does not yield successful defibrillation a right parasternal lead position may provide an alternative EO When defibrillation testing is judged unsafe on clinical grounds a low PRAETORIAN score (<90) may be an acceptable surrogate for successful conversion 65 For primary prevention implants, dual zone programming is advisable with a conditional zone starting at 200 b.p.m. and shock zone starting at 250 b.p.m. with 80J output 51,52 A TV-PM or LCPM may be added to a non-TV-ICD in patients that develop a need for pacing EO BMI, body mass index; LCPM, leadless cardiac pacemaker; PM, pacemaker; S-ICD, subcutaneous implantable cardioverter defibrillator; TV, transvenous. Open in new tab Future directions As with TV defibrillators, the S-ICD compensates for low R-wave amplitude by increasing sensitivity. However, in some patients (such as those who develop right bundle branch block or slow VT), this can lead to oversensing and IASs. Algorithms using a combination of multiple templates and sensing vectors, may improve arrhythmia discrimination, while mathematical transformation of the sensing vector may increase the R:T ratio, increasing the proportion of patients passing the screening test for S-ICD implantation. The current S-ICD generator is still twice as large as its TV counterparts as it requires hardware to provide 80J shock capacity and a large battery to ensure device longevity. It is possible that new device/shock lead configurations and shock waveforms may reduce the energy requirement for defibrillation. If so, this may permit a smaller generator (with associated benefits for specific patient populations), eliminate the need for defibrillation testing, and increase device longevity. The hardware of the current generation of the S-ICD, and higher pacing thresholds as well as physical discomfort of extra-thoracic pacing limits its use to patients with no guideline pacing indication. The emergence of the LCPM offers bradycardia pacing in a modular approach without compromising the leadless concept. In addition, conductive communication between the S-ICD and LCPM enables antitachycardia pacing, creating a hybrid modular approach for arrhythmia treatment based on clinical need. The EMPOWER pivotal trial is currently evaluating this concept.65 The extravascular implantable cardioverter defibrillator Background The extravascular implantable cardioverter defibrillator (EV-ICD) is currently in the final stage of investigation before it may be granted permission for routine clinical use. Like the S-ICD, it avoids the risks associated with TV defibrillation leads. The EV-ICD device is implanted in a similar location to the S-ICD, in a left lateral position of the thorax, but the defibrillation/sensing lead is placed behind the sternum in the anterior mediastinal space (Figure 7A). Proximity of the lead to the heart allows for lower energy defibrillation and a device comparable in size and longevity to a TV-ICD. This proximity may also permit pacing to treat asystole and ventricular tachycardia. The EV-ICD can deliver shocks up to 40J and has circuits designed for retrosternal sensing and pacing. The lead is epsilon shaped (Figure 7B) with two pace/sense electrodes and two 4 cm defibrillation coil segments, that are connected for defibrillation to effectively form an 8 cm electrode. The system has multiple potential pacing and sensing vectors using these four electrodes and the can. Figure 7 Open in new tabDownload slide (A) The EV-ICD lead is implanted under the sternum while the device sits in a posterolateral thoracic position, and (B) has a double S-shaped with two 4 cm coils and two electrodes for sensing, pacing, and defibrillation (reproduced with permission of Medtronic). Overview of studies The retrosternal space was first used to achieve defibrillation in 2007 when Tung et al.66 reported successful defibrillation using conventional defibrillators connected to TV leads implanted into this space from a superior approach in three patients. In 2012, the EV-ICD was conceived with a design to allow pacing and defibrillation with energy levels similar to a TV-ICD but from the anterior mediastinal space. The first human study67 confirmed that substernal defibrillation was feasible with energy available in current TV-ICDs, with successful defibrillation in 13 of 14 subjects at 35J, using a conventional defibrillation lead.67 A second human study evaluated retrosternal pacing in 26 patients using an electrophysiology catheter.68 Ventricular capture was achieved in 18 subjects, with a threshold of 5.8 ± 4.4 Volts at 10 ms, with bipolar R-wave amplitudes of 0.83–3.95 mV. The third human clinical feasibility study69 evaluated pacing and DFTs using the EV-ICD lead temporarily placed in the substernal space. In 79 patients, the median implantation time was 12.0 ± 9.0 min. Ventricular pacing was successful in at least 1 vector in 76 of 78 patients (97.4%), without evident capture of skeletal muscle in 72 of 78 (92.3%). A 30J shock successfully terminated 104 of 128 episodes (81.3%) of ventricular fibrillation in 69 patients. In the Pilot EV-ICD study in 2018, the first permanent implants were successfully performed in 20 of 21 patients. Induced VA were successfully terminated in 18 patients (90%), and pacing capture was achieved in 19 patients (95%).70 Sensing with non-TV-ICDs poses challenges because the ventricular signals are of lower amplitude. The sensing algorithm of the EV-ICD is more akin to that of a TV system than the S-ICD, with additional features including an increased minimum sensitivity of 0.075 mV. In the pilot study all patients had R waves >1 mV (mean 3.4 ± 1.7 mV) and detected ventricular fibrillation at a sensitivity of ≥0.3 mV. One patient had an IAS, due to P-wave oversensing.70,71 The EV-ICD is currently being evaluated in the pivotal EV-ICD study,72 which commenced in June 2019, with a target of at least 292 patients implanted. Following a pause due to the COVID-19 pandemic, recruitment was completed in September 2021. Implantation of the extravascular- implantable cardioverter defibrillator Implantation of the EV-ICD requires a thorough understanding of the variations of retrosternal anatomy. A pre-implant chest computed tomography may be useful to guide lead and can placement. At implantation anatomical landmarks should be drawn, fluoroscopy in multiple directions is needed. Access to the retrosternal space is made via an incision from the tip of the xiphoid to the costal margin. The rectus sheath is exposed, then blunt dissection beyond the rectus fascia and through the diaphragmatic attachments is performed to access the retrosternal space. Tunnelling along the posterior aspect of the sternum uses a bespoke blunt instrument to safely guide placement of a sheath through which the lead is inserted. Tunnelling is performed with lateral fluoroscopy, maintaining contact with the posterior sternum to avoid cardiac injury.69,70 On-site cardiothoracic surgical backup is currently mandated. The device is placed subcutaneous in the left chest in the mid-axillary line against the fascia (Figure 8).70,71 Implantation requires a sensed R wave >1 mV, and successful defibrillation testing with a margin of at least 10J. Figure 8 Open in new tabDownload slide Extravascular lead is implanted substernal and connected to the left lateral subcutaneous ICD. Implantation so far has only been performed during clinical trials under deep sedation or general anaesthesia in the setting of an operating room by electrophysiologists with a cardiac surgeon as backup for emergency, both trained for the procedure. A fatal cardiac injury with tamponade occurred early in the acute human study, prior to development of the current tunnelling tool and implant technique. No subsequent implant complications were observed in the relatively small number of patients in the acute study or in the Pilot study.70,71 Further experience will clarify the risk of cardiac injury and other implant complications, relative to those with the S-ICD and TV-ICD. Patient selection for the extravascular implantable cardioverter defibrillator Like the S-ICD, the EV-ICD is suitable for patients that require protection from sudden death due to ventricular tachycardia or ventricular fibrillation. While it has greater pacing capability than the S-ICD, pacing requires higher energies than TV systems and is perceptible to patients. The current pacing capability is considered adequate for protection against unexpected asystole. The current device is not suited for patients that require active pacing for bradycardia or re-synchronization therapy. Implantation of the EV-ICD has so far only been attempted in patients in whom the anterior mediastinal space has not been modified by previous cardiac surgery or other conditions that could potentially fibrose this space. Marked sternal deformity, especially pectus excavatum, is also currently considered a contraindication to EV-ICD implantation. Future developments of the extravascular implantable cardioverter defibrillator The current EV-ICD is a first-generation device with only limited published data, and is not yet commercially available. It is designed to be MRI conditional, with remote care capability and longevity similar to current TV-ICD platforms. A large clinical trial for CE and FDA approval has finished enrolment and outcome data are foreseen in the second half of 2022.72 Based on the currently available information it appears that it can be implanted with reasonable safety, and can detect and defibrillate induced ventricular fibrillation during testing. As such, it can be seen when compared with the S-ICD, offering similar therapy, but with a more complex implant, that is potentially more hazardous. However, it has the potential advantages of greater longevity, smaller size, and greater pacing capability. As the sensing algorithm is different from the S-ICD, it may not be as susceptible to T-wave oversensing, but the lead location may make it more susceptible to P-wave oversensing. Pacing capability at present appears to be limited by high thresholds and awareness of pacing. Future lead and algorithm modifications may improve sensing and pacing performance, and widen clinical indications. Supplementary material Supplementary material is available at Europace online. Acknowledgements The authors thank the EHRA Scientific Document Committee: Dr Nikolaos Dagres, Prof. Thomas Deneke, Prof. Arthur Wilde, Prof. Frank R. 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TI - Practical considerations, indications, and future perspectives for leadless and extravascular cardiac implantable electronic devices: a position paper by EHRA/HRS/LAHRS/APHRS 
JF - Europace
DO - 10.1093/europace/euac066
DA - 2022-08-01
UR - https://www.deepdyve.com/lp/oxford-university-press/practical-considerations-indications-and-future-perspectives-for-dOdot7n1us
SP - 1691
EP - 1708
VL - 24
IS - 10
DP - DeepDyve
ER -