2025 HFA／EHRA 临床共识声明：心脏植入电子和 其他监测装置在连续血流左心室辅助装置患者中的应用

Cardiac implantable electronic and other monitoring devices in continuous-flow left ventricular assist device patients. A clinical consensus statement of the Heart Failure Association and the European Heart Rhythm Association of the ESC

Offer Amir 1 \* , Stamatis Adamopoulos 2 , Haran Burri 3 , Antoni Bayes-Genis 4 , Christophe Leclercq 5 , Maja Cikes 6 , Anastasia Egorova 7,8 , Petr Peichl 9 , Marat Fudim 1 0, 11 , Archana Rao 1 2 , Finn Gustafsson 1 3 , Sergio Richter 1 4 , Matteo Pagnesi 1 5 , Giuseppe Rosano 1 6, 1 7 , Frank Ruschitzka 1 8, 1 9 , and Jens Cosedis Nielsen 20

1 Heart Institute, Hadassah University Medical Center and Faculty of Medicine, Hebrew University, Jerusalem, Israel; 2 Heart Failure-Heart Transplant-Mechanical Circulatory Support Unit, Onassis Cardiac Surgery Center, Athens, Greece; 3 Cardiac Pacing Unit, Cardiology Department, University Hospital of Geneva, Geneva, Switzerland; 4 Institut del Cor Germans Trias i Pujol, CIBERCV, Barcelona, Spain; 5 Department of Cardiology, University Rennes, Rennes, France; 6 University of Zagreb School of Medicine, Department of Cardiovascular Diseases, University Hospital Center Zagreb, Zagreb, Croatia; 7 CAHAL, Center for Congenital Heart Disease Amsterdam Leiden, Leiden University Medical Center, Leiden, The Netherlands; 8 Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; 9 Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 1 0 Division of Cardiology, Department of Medicine, Duke University, Durham, NC, USA; 11 Duke Clinical Research Institute, Durham, NC, USA; 1 2 PG Dip Cardiology, GPSI Cardiology, Liverpool Heart and Chest Hospital, Liverpool, UK; 1 3 Department of Cardiology, Rigshospitalet, University of Copenhagen, København, Denmark; 1 4 Department of Cardiology, Heart Center Dresden, University Hospital, Technischen Universität Dresden, Dresden, Germany; 1 5 Institute of Cardiology, ASST Spedali Civili, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy; 1 6 Chair of Pharmacology, Department of Human Sciences and Promotion of Quality of Life, San Raffaele University of Rome, Rome, Italy; 1 7 Department of Cardiology, San Raffaele Cassino Hospital, Cassino, Italy; 1 8 Department of Cardiology, University Heart Center, University Hospital Zurich and University of Zurich, Zurich, Switzerland; 1 9 Center for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; and 20 Department of Cardiology, Aarhus University Hospital and Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

Received 30 October 2024; revised 3 February 2025; accepted 2 1 February 2025

The management of heart failure patients with continuous-flow left ventricular assist device (LVAD) patients is challenging. While one third of these patients are recipients of cardiac implantable electronic devices (CIEDs), the risk for atrial and ventricular arrhythmias may coexist. The lack of large datasets and dedicated randomized controlled trials (RCTs) focusing on LVAD and CIED implantation and management has brought medical centres to develop their own protocols and guidelines. This clinical consensus statement of the Heart Failure Association and the European Heart Rhythm Association of the ESC is a joint effort to summarize the current literature and provide advice on patient management within this field.

Left ventricular assist device • Cardiac implantable electronic device • Pacemaker • Cardiac resynchronization therapy • Remote monitoring

\*Corresponding author. Heart Institute, Hadassah University Medical Center and Faculty of Medicine, Hebrew University, Jerusalem, Israel. Tel: + 972 2 6775266, Fax: + 972 2

6775270, Email: oamir@hadassah.org.il

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Introduction

Large subgroups of patients with advanced heart failure (HF) are treated with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy (CRT) devices, recommended according to current guidelines. 1 With improved survival, more of these patients progress to advanced HF, and use of continuous-flow (CF) left ventricular assist devices (LVADs) in patients with cardiac implantable electronic devices (CIEDs) is thus increasingly common. In the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3), approximately $35\%$ of patients in the cohort were recipients of a CRT defibrillator (CRT-D) or pacemaker (CRT-P) at the time of LVAD implantation and more than two thirds had an ICD. 2,3 Furthermore, survival continues to improve in LVAD carriers, and the group of patients with co-implanted CIEDs and LVADs is expected to increase.

Patients with LVADs are at risk for ventricular arrhythmias (VAs), especially those with a preimplant history of VA and those who are in the early post-LVAD implantation phase. 4 Various acute electrophysiological alterations after LVAD placement may play a role for arrhythmic risk. 5 Haemodynamic instability is less likely to occur during VA, while the patient is on LVAD support and thus not dependent on the intrinsic cardiac pulse. 6

The lack of large datasets and dedicated randomized controlled trials (RCTs) focusing on LVAD and CIED implantation and management has brought medical centres to develop their own protocols and guidelines. In a Cleveland Clinic retrospective study, 7 more than $20\%$ of patients equipped with an ICD before LVAD implantation required procedures related to their ICD after LVAD implantation, ranging from a pulse generator exchange to complete system removal. Although half the patients without an ICD underwent implantation after they received an LVAD, ICDs were not associated with lower mortality. Of note, ICD-associated infections were observed in $3\%$ of the LVAD patients. 7

While some centres routinely deactivate left ventricular (LV) lead pacing and program right ventricular (RV) backup pacing only in LVAD patients with CRT, 8 current European Society of Cardiology (ESC) guidelines do not provide any clinical or practical recommendations on how to manage CIEDs pre-, peri- or post-LVAD implantation. Nor does any clinical reference exist on how to manage CIEDs in LVAD patients in situations of acute arrhythmia such as an electrical storm (ES), or on the management of CIED-related complications. The present manuscript, commissioned by the European Heart Rhythm Association (EHRA) and the Heart Failure Association (HFA) of the ESC, is a joint effort to summarize the current literature and provide advice on patient management within this field ( Figure 1 ).

Cardiac implantable electronic devices before and after left ventricular assist device implantation – primary and secondary prevention of ventricular arrhythmias

Approximately $80\%$ of patients undergoing LVAD implantation in the USA carry a CIED, 9, 1 0 however, this proportion is far lower in European LVAD populations where it ranges between $54\%$ for ICD or CRT-D in the European PCHF-VAD registry and $58\%$ for ICDs in EUROMACS. 11 While most experience is with transvenous ICDs and CRT devices, recent literature indicates that LVAD implantation is also feasible in most carriers of subcutaneous ICDs (S-ICD). 1 2 No experience on LVAD implantation in patients with an extravascular ICD has been published. 1 3 Although the presence of VA pre-LVAD predicts the occurrence of VA following LVAD implantation, 1 4, 1 5 pre-implant ICD shocks do not seem to be associated with unfavourable post-implant clinical outcomes, except for hospitalizations for ICD shocks per se . 1 5 However, it has been demonstrated that VAs occurring after LVAD implantation are associated with a greater than twofold increase in the risk of cardiovascular and all-cause death. 1 6

The VT-LVAD score ( Table $\mathit{1)^{14}}$ has been proposed as a tool for stratifying patients for their risk of VA post-LVAD implantation. This can help guide decisions regarding CIED use, ventricular assist device (VAD) configuration (LVAD vs. bi-VAD) and transplant urgency listing.

In line with the above, presence of an ICD or CRT-D in patients with LVADs has not convincingly been shown to correlate with long-term outcomes, including mortality. 9, 1 7 In an analysis of 448 patients with CF LVADs implanted across 1 2 European tertiary referral centres between 2006 and 20 1 8, presence of an ICD or CRT-D was associated with a substantially lower risk of 1 -year all-cause mortality after LVAD implantation as compared to LVAD carriers without an ICD or CRT-D. 1 6 Albeit extensive adjustments were done supporting these findings, residual confounding effects may have driven these differences, as the patients in the non-ICD group were more severely ill, more frequently being in INTERMACS profile 1 , on extracorporeal membrane oxygenation support and on ventilator prior to LVAD implant. Moreover, the main difference in survival between the groups was seen within the first 90 days post-LVAD implantation.

In an analysis of 524 LVAD patients enrolled between 2008 and 20 1 7 in the multicentre Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry, presence of a CRT-D was associated with an increased risk of late RV failure (hazard ratio 2.85; $95\%$ confidence interval 1 .42–5.72, $\scriptstyle\phi\,=\,0.003$ ), 9 which may have been attributed to LV lead pacing. A recent, randomized, cross-over study of 30 patients with LVADs and CRT showed improved functional capacity and quality of life as well as a lower burden of arrhythmias with RV when compared with biventricular (BiV) pacing. 1 8

Advice tables

  |AdviceTODO|| |---|---| |Close attention to programming CIED bradycardia and tachycardia parameters|OPN| |to avoid sensing issues, minimize shocks and preserve battery longevity to|| |avoid generator replacements (and their complications), is advised.|| |In the immediate post-operative period following LVAD implantation,|OPN| |multidisciplinary team based CIED management involving the heart failure|| |team, electrophysiology/CIED team, patient and families/caregivers is|| |advised||

Figure 1 General considerations and advice for conduction system pacing implantation. Numbering the advices in one row from no. 1 mentioned first and no. 2 1 mentioned last, in the voting among the 1 6 authors, there was ${\tt>}90\%$ agreement for advices no. 1 3, 1 4, 1 5 and 1 8, ${>}85\%$ agreement for advice no. 1 6, and $100\%$ agreement for the remaining advices. AD, antiarrhythmic drug; ATP, anti-tachycardia pacing; CIED, cardiac implantable electronic device; CRT, cardiac resynchronization therapy; CRT-D, cardiac resynchronization therapy with defibrillator; HF, heart failure; ICD, implantable cardioverter-defibrillator; LV, left ventricular; LVAD, left ventricular assist device; RV, right ventricular; VA, ventricular arrhythmia.

| In patients with LVAD and battery depletion of an implanted CIED, careful OPN reassessment of a continued need for active CIED therapy is advised before proceeding to CIED replacement. || |---|---| | Manage CIED complications in LVAD patients as in the non-LVAD population, with a special focus on concomitant LVAD driveline infection in case of CIED infection and on right HF in case of lead-induced severe tricuspid regurgitation. |OPN| | Manage patients with electrical storm and LVAD in specialized centres experienced in the management of patients with VAs. |OBS| | Interrogation of an ICD with meticulous evaluation of all stored arrhythmia episodes is advised in case of recurrent VAs to evaluate the appropriateness and effectiveness of device therapies and programming. |OBS| |Consider ICD therapy in LVAD recipients with symptomatic sustained VAs.|OBS| | In patients with single-chamber device and severe sinus bradycardia or chronotropic incompetence, an upgrade to a system capable of atrial pacing may be performed. |OPN| | Perform CIED-related procedures in high-volume centres experienced in LVAD therapy to minimize complications. |OPN| | In LVAD patients carrying an CIED capable of automatically transmitting predefined alerts, remote monitoring is advised to monitor for the occurrence of sustained VAs (to avoid right-sided heart failure), atrial tachyarrhythmias (to avoid inappropriate ICD shocks) and technical issues. |OPN|

Figure 1 Continued.

Figure 1 Continued.

| Make LVAD patients at end-of-life aware of the option of turning off the ICD tachy therapies. |OPN| |---|---| | Timely discussion of ICD programming during an end-of-life with LVAD patients and relatives. |OPN| |May be appropriate TO DO|| | Temporary deactivation of ICD shock therapy to prevent unnecessary therapies in case of frequent VAs that can be terminated by ATPs and/or AADS. |OPN| |Lead extraction in selected LVAD patients with CIED complications.|OPN| | Turning off LV lead pacing in an implanted CRT device to conserve battery and avoid avoidable pulse generator replacement procedures. |OPN| | In patients with a pre-existing CRT-D device, careful consideration should be given to whether to turn off the LV lead pacing and to replace it by RV only pacing or back-up pacing after LVAD implantation. |OPN| | Use of an absorbable antibacterial envelope at the time of intervention in patients with high-risk for CIED infection. |OPN| | Use of an implantable loop recorder with remote monitoring to detect sustained VAs in selected LVAD patients not carrying a CIED. |OPN|

On the other hand, CIED-related procedures after LVAD implantation are associated with more complications. The incidence of complications approaches $20\%$ in CIED procedures post-LVAD, driven almost entirely by pocket haematoma, with one study showing a trend towards lower incidence during de novo CIED implantation as opposed to revision procedures in patients who were

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already CIED carriers, 1 9 and another showing infection only in patients who developed post-operative pocket haematoma. 20 A third study reported a 3.5-times higher risk of clinically significant pocket haematoma and/or CIED infection among patients undergoing generator revision or replacement with versus without LVAD. 2 1 Currently the preferred approach in most centres is to implant

|Advice NOT TO DO|| |---|---| | Upfront implantation of an ICD as a primary preventive measure in all patients due to receive or who just received an LVAD is not prudent unless in patients with a notable burden of ventricular arrhythmia prior to LVAD implantation. |OPN| |Upgrade to CRT is not advised in LVAD recipients.|OBS| | Considering an increased risk for infection and bleeding with exchange procedures, it is advised not to do complex CIED-procedures. |OPN|

Figure 1 Continued.

CIEDs in LVAD patients on un-interrupted vitamin K antagonist (VKA) anticoagulation rather than using anticoagulation bridging. Of note, an aspirin-sparing regimen in HeartMate 3 patients was recently shown to be non-inferior to combination therapy with a VKA and aspirin. 22

While S-ICDs overcome many of the transvenous lead-related risks, their use is limited by the lack of anti-tachycardia pacing (ATP) modalities, which are important in LVAD patients who generally tolerate VA well and in whom all efforts should be made to avoid conscious shocks. 23 An important consideration on S-ICDs in LVAD patients is the high risk of electromagnetic interference (EMI), which may result in inappropriate shock therapy from the ICD. 1 2 Data regarding leadless pacemakers in LVAD patients are lacking but these have been successfully implanted in patients with LVADs without reported evidence of EMI or device-to-device interaction. However, transcatheter pacing system (Micra™, Medtronic, Minneapolis, MN, USA) interaction requiring device repositioning has been reported. 24 Further studies are needed to evaluate the safety and efficacy of leadless devices in this unique cohort of patients.

Cardiac implantable electronic device programming in left ventricular assist device patients

Adequately powered RCTs to assess the potential of CIED therapy to guide antiarrhythmic or ablation therapy in LVAD recipients are lacking. 1 6,25–27

||Table 1 The VT-LVAD score|| |---|---|---| |VT-LVAD|Variables|Score| ||VAs prior to LVAD implantation|2points| |一|Therapy: no ACE-inhibitor post-LVAD|2points| ||FaiLure duration (>12 months)|2points| ||VAs post-LVAD implantation (||

The VT-LVAD score identified four risk groups: low (score 0 to 1 ), intermediate (score 2 to 4), high (score 5 to 6) and very high (score 7 to 1 0). The risk of ventricular arrhythmias (VAs) at 1 year were 0%, $8\%$ , $31\%$ and $55\%$ , respectively. 1 4 ACE, angiotensin-converting enzyme; LVAD, left ventricular assist device.

The incidence and prevalence of VAs in LVAD patients have been reported to be as high as $50\%$ , and incidence of ICD shocks to range between $16\%$ and $42\%$ , most of which occur during the first 30 days after implantation. 25 While VA incidence varies depending on the underlying type of cardiomyopathy, LVAD recipients are at risk of developing de novo monomorphic ventricular tachycardia (VT), irrespective of their pre-LVAD implantation VT history. Haemodynamic support in LVAD patients enables them to tolerate arrhythmias which are commonly lethal in patients without mechanical circulatory support and to even have ‘walk-in’ VT or ventricular fibrillation (VF). 25 ICD recipients on such support are likely to fully experience painful shocks. To reduce the number of shocks, ‘monitor-only’ zones for slow VT or only multiple painless ATP sequences can be programmed. The first shock in VT zones can be low, as even ${<}1$ J shocks can effectively

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Table 2 Programming of implantable cardioverter-defibrillator tachycardia detection and therapy parameters for primary prevention of sudden death in left ventricular assist device patients

|Manufacturer| Detection|Therapy| |---|---|---| |Abbott|VT-1 zone: Monitor only (170 bpm); VT-2 zone:|VT-1: Monitor; VT-2: Burstx5 (87% CL, 10 stimuli/burst);| || 190 bpm* (100 intervals, 6 interval redetection); VF zone: 250 bpm (100 intervals, 6 interval |Rampx5 (88%, 8 stimuli/sequence), max output | || VF zone: 250 bpm (100 intervals, 6 interval redetection) |shockst; VF: ATP before charge, max output shocks| |Biotronik|VT-1 zone: Monitor only (170 bpm); VT-2 zone:|| |Biotronik|190 bpm* (80 intervals, 20 interval redetection);|VT-1: Monitor; VT-2: Burstx5 (85% CL, 10 stimuli/burst);| ||VF zone: 250 bpm-30/40 intervals; Redetect: 12/16| Rampx5 (90%, 8 stimuli/sequence), max output shockst; VF: ATP before charge, max output shocksshockst; VF: ATP before charge, max output shocks VT-1: Monitor; VT-2: Burstx5 (87% CL, 10 stimuli/burst); | |Boston Scientific|VT-1 zone: Monitor only (170 bpm); VT-2 zone:|| |(transvenous)|190 bpm* -60 s (max given monitor zone);|Rampx5 (88%, 8 stimuli/sequence), max output | ||VF zone: 250 bpm-15 s; Redetect: 1 s| shockst; VF: ATP before charge, max output shocks| |Boston Scientific (S-ICD)| Conditional zone: 200 bpm; Shock zone: 230 bpm|Max output shocks (cannot program less); Max output | |Medtronic|Monitor: 154 bpm-110 intervals; VT zone:|shocks (cannot program less)| |Medtronic|167 bpm-100 intervals; FVT zone (via VT):| FVT: Burstx5 (88% CL, 10 stimuli/burst), Rampx5 (88% CL, 8 stimuli/sequence), max output shocks; | ||188 bpm*; VF zone: 250 bpm-30/40 intervals;|VF: ATP before/during charge, max output shocks| | Microport|Redetect: 12/16 intervals|| | Microport|Slow VT zone: 150 bpm-200 intervals; FVT zone:|FVT: Burstx5 (85% CL, 10 stimuli/burst), Rampx5| | Microport|190 bpm*-200 intervals; VF zone: 240 bpm-20|(85% CL, 8 stimuli/sequence), max output shockst;| ||intervals|VF: max output shocks|

Modified from Parikh et al. 28 ATP, anti-tachycardia pacing; CL, closed loop; FVT, fast ventricular tachycardia; S-ICD, subcutaneous implantable cardioverter-defibrillator; VF, ventricular fibrillation; VT, ventricular tachycardia. \*In patients † Optionally consider a first low-energy shock ( ${\tt<}40$ years of age, program cutoff to 200 bpm (or closest value). ≤ 1 0 J).

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cardiovert monomorphic VT. 26 However, low-energy shocks are usually still painful, and, if ineffective, subsequent shocks are perceived as being more painful than initial discharges. 27 The programmed detection duration should be maximized to avoid treating non-sustained VA, as proposed in a 20 1 9 American Heart Association scientific statement. 1 6 Timeouts for supraventricular tachycardia discrimination and ATP should be deactivated. A single-centre prospective randomized trial in 83 patients compared an ultra-conservative ICD programming strategy with maximal allowable intervals to detection in the VT and VF zones (corresponding to arrhythmia durations of $\leq\!60\,s_{.}$ ) with standard ICD programming. Ultra-conservative programming was shown to be safe, however with no significant differences in occurrence of ICD shocks between the two groups. 26 It should nevertheless be borne in mind that the therapies were identical in both groups, and that shocks may have been reduced by increasing the number of ATP sequences with ultra-conservative programming. Proposed programming of ICD tachycardia settings is shown in Table 2 .

Interaction between LVADs and CIEDs can result in failure to communicate by telemetry (LVAD manufacturer websites list CIED models for which this problem has been reported), sensing issues, or a magnetic effect on the CIED.

Oversensing of EMI emitted by LVADs can lead to inappropriate VA detection and therapy including shock delivery or to pacing inhibition resulting in asystole, which may be asymptomatic. Inductive telemetry by the programmer head

can create a magnetic field which can disrupt the alignment of the magnetically levitated rotor of HeartMate 3 LVAD. Potential issues and the suggested troubleshooting strategies are outlined in Figure 2 . 29

Electrical storm in left ventricular assist device patients – risk and management

Recurrent VAs represent one of the most common clinical problems after LVAD implantation. ES is defined as ${>}3$ sustained episodes of VT, VF or appropriate ICD shocks during a 24-h period, and has been reported in $9{-}28\%$ of this population. 26,30,3 1 ES occurs most frequently within the first month post LVAD-implantation, after which the incidence tends to decrease, likely due to LVAD-driven unloading and reverse ventricular remodelling. However, the arrhythmic substrate can progress later, and the risk of VAs increases again beyond the third year after LVAD implantation. ES is most commonly associated with a previous history of VAs, a long history of $\mathsf{H F},^{30}$ antiarrhythmic drug use, and perioperative mechanical circulatory support around LVAD implant. 3 1

Electrical storm in LVAD patients is strongly associated with increased early all-cause mortality. 3 1 One-third of patients die within 1 5 days, with most deaths being directly due to ES. In the remaining patients, a negative impact on hospitalization rates and

 Figure 2 Potential device–device interaction between left ventricular assist devices (LVADs) and cardiac implantable electronic devices (CIEDs) and their troubleshooting and management strategy. Reproduced, with permission, from Tanawuttiwat et al. 29 The low-frequency attenuation (LFA) filter (designed to reduce T-wave) may worsen electromagnetic interference. EMI, electromagnetic interference; ICD, implantable cardioverter-defibrillator; RA, right atrial; RV, right ventricular.

quality of life has been described. About one-third of patients have a recurrence of ES, within a median of 43 days after the initial ES. 30

The mechanical haemodynamic support provided by the LVAD usually allows transfer of patients to centres specializing in the management of patients with LVADs and VA. For patients with ES, a multi-faceted approach is often required, including ICD reprogramming when appropriate, antiarrhythmic drug therapy, sedation and catheter ablation. This section will focus on CIED management during ES.

In patients with ES, all CIEDs should be interrogated, and all stored episodes should be reviewed to comprehend the

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mechanism of the initiation of the arrhythmia and effectiveness of ATP/shock therapy. In the case of polymorphic VAs, attempt should be made to record the triggering ventricular ectopy, if present.

Inappropriate ICD therapy can be triggered by non-sustained VTs (e.g. due to suction events). Recurrent ICD shocks may trigger further hyperadrenergic state which may be associated with additional VAs, are traumatic events leading to psychological disorders and higher mortality. Most VAs are temporarily well tolerated with LVAD support and thus, ICD shock therapy might be deactivated, and VA might be terminated by commanded ATP or antiarrhythmic drugs.

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Increasing the base pacing rate (overdrive pacing) can be used to suppress bradycardia-induced VAs and frequent ventricular ectopy to avoid short-long-short sequences. 32 For patients with CRT devices, reprogramming from BiV to RV-only pacing was associated with lower risk of VAs and may be appropriate in case of ES. 1 8,33 Of note and as is further elaborated in the ‘CRT in LVAD patients – haemodynamics and potential recovery’ section, some studies have suggested an association between interrupted CRT in LVAD patients and worsened VA outcomes. 34 Thus, a patient-specific approach is needed.

Managing cardiac implantable electronic device complications in left ventricular assist device patients

A growing population of LVAD recipients has pre-existing CIEDs in situ that can contribute to morbidity. ICD placement carries important risks including haematoma, device infection, and inappropriate therapy. Such procedures should be undertaken collaboratively in consensus with the electrophysiologist/device-implanting specialist, the LVAD team and the patient and caregivers. 35–37 Beyond peri-procedural complications in patients with LVAD who require a CIED procedure, 1 9,20 the overall medium to long-term risk of CIED-related complications seems significant, including infection, CIED-related tricuspid regurgitation, lead fracture, dislodgement and EMI. 7,38–4 1

Infection is one of the most serious CIED complications and is associated with significant morbidity and mortality. 42,43 The management of CIED infection entails a full system extraction, alongside with appropriate antibiotic therapy. Data on the incidence, presentation, management, and clinical outcomes of CIED infection in LVAD patients are limited. 38,39,44,45

Left ventricular assist device driveline infections have been found to be associated with post-LVAD ICD-related procedures, 46 and management can be challenging. Beyond short-term antibiotic therapy and chronic suppressive antibiotic therapy, particularly in patients with pre-existing or concomitant LVAD infection, complete CIED extraction is feasible and has been reported to be safe in LVAD patients. 38,39,44,45 Lead extraction can also be appropriate in other scenarios, such as recurrent VAs attributable to transvenous leads, 25 lead fracture, dislodgment or malfunction imposing a significant short-term risk for the patient, 25,28,38 and lead-induced severe tricuspid regurgitation, which may be particularly detrimental in LVAD patients due to the risk of right-sided HF. 47–50 A lower threshold for CIED extraction could potentially be implemented in case of relevant CIED complications in patients with CF-LVAD. However, literature on extraction risk in LVAD carriers is scarce, and a careful balance of the procedure-related risks should be performed, considering the relative risk of complications of CIED extraction per se , 5 1 –53 and the high-risk nature of the LVAD population. In the absence of conclusive evidence and dedicated guidelines, management of CIED complications in LVAD patients (including lead extraction) should be based on current expert

consensus statements. 42,54 Given the complexity of the LVAD population and the management of CIED complications in this setting, a multidisciplinary evaluation involving the LVAD team, the electrophysiology/CIED team, the cardiac surgeons and – when appropriate – the infectious disease team is warranted. 25

Upgrade and cardiac implantable electronic device pulse generator exchange procedures

VAs are common and usually well-tolerated in patients supported by LVADs. 55 However, VAs are associated with an increased risk of mortality. 1 6,56–58 Although the contribution of ICDs to improved survival in patients with CF-LVAD remains controversial, upgrade to ICD therapy should be performed in patients who experience symptomatic sustained VAs with haemodynamic compromise. 59 In patients with a single-chamber device and severe sinus bradycardia or chronotropic incompetence, an upgrade to a system capable of atrial pacing should be performed. 1 The benefit of CRT in LVAD recipients remains unclear. 1 8,34,60 In several previous studies, CRT failed to reduce mortality and hospitalizations but was associated with significant device-related complications and increased VA burden. 34,6 1 ,62 A recent prospective cross-over RCT involving patients with CF-LVAD and CRT, noted superior clinical outcomes of RV pacing over BiV pacing. 1 8 Unless future RCTs demonstrate significant benefit, upgrade to CRT should currently not be performed in LVAD patients. An implanted LV lead may be deactivated to conserve battery and avoid unnecessary device replacement. Considering the increased risk of infection and bleeding with exchange procedures, 20 complex procedures should be avoided. In patients with high-risk for CIED infection, use of an absorbable antibacterial envelope may be appropriate, according to current guidelines. 1 To minimize complications, the procedures should be performed in high-volume centres experienced in LVAD therapy.

Management and continuation of cardiac implantable electronic device therapy following left ventricular assist device explantation due to myocardial recovery

In some cases, LVAD support can rehabilitate a failing heart, raising the possibility of device removal and return to medication-based treatment. Approximately $2\%$ of LVADs are explanted within 5 years of the initial implant. 63 Studies estimate that LVAD use in treating LV failure leads to myocardial recovery mainly in non-ischaemic aetiology. 64 The most significant myocardial reverse remodelling typically occurs within the first year after LVAD implant. The mid- to long-term outcomes after LVAD explantation are encouraging, with $88\%$ of the patients surviving without heart transplant, LVAD reimplantation, or relapse of advanced HF at

24 months of follow-up. Furthermore, the majority of patients experienced mild HF symptoms only (New York Heart Association class II). 65 However, the risk of recurrent HF after LVAD removal in patients initially treated as a bridge to recovery, is significant. Even in patients meeting the clinical criteria for LVAD explantation, there is a persistent molecular signature of HF, which suggests only partial response. Long-term freedom from HF recurrence is an important goal, but even in medically treated HF patients with a recovered LV ejection fraction, there is an ongoing risk for HF recurrence, suggesting myocardial remission and incomplete recovery. 66 The decision to continue or remove CIEDs should be based on a thorough risk–benefit analysis. This includes weighing the risks of device-related complications (infections, lead problems) against the potential benefits of CIEDs for ongoing arrhythmia management or pacing needs in case of HF recurrence. If the decision is made to continue CIED therapy, programming adjustments may be necessary. The pacing parameters, sensing thresholds and detection settings should be optimized based on the patient’s present cardiac status, which would in turn influence the need for generator replacement.

Cardiac resynchronization therapy in left ventricular assist device patients – haemodynamics and potential recovery

More than one-third of advanced HF patients are carriers of a CRT device at the time of LVAD implantation. Whether and to what degree CRT provides meaningful clinical benefit with long-term LVAD support or may even be harmful in a subset of patients, is a matter of ongoing debate. Randomized clinical outcome trials are lacking and the currently available results from observational studies, which are at large limited by small sample size and inherent bias, suggest that cardiac resynchronization does not improve morbidity and mortality in patients with a LVAD. 2,25–27,34,67,68

Of note, advanced HF patients who require LVAD therapy are often CRT non-responders. Conceptually, an incremental benefit with BiV pacing in the setting of LVAD therapy in patients who did not respond to CRT before LVAD implantation is unlikely.

parameters, including wedge pressure and cardiac output, did not differ between any of the pacing modes. While only short-term data were presented, the investigators questioned the putative benefit of CRT pacing over RV-only pacing.

In a recent multicentre study in 488 patients, continued CRT, compared with ICD only programming after LVAD implantation, resulted in a significantly higher need for pulse generator changes in the CRT group. 68 Hence, turning off the LV lead pacing will prolong battery life and might decrease the need for avoidable pulse generator replacement procedures, and associated morbidity.

Conceptually, the effect of the lack of pulsatility, i.e. non-pulsatile, non-laminar blood flow without a palpable pulse of most CF pumps, on autonomic regulation, vascular and microcirculatory function, may account, in part, for the lack of benefit of cardiac resynchronization in VAD patients.

Physiologically, several mechanisms may account for the lack of benefit of BiV pacing in LVAD patients. Importantly, any potential benefit of LV pacing on improving electrical dyssynchrony and on loading characteristics is likely to be overshadowed by the continuous unloading by the LVAD. In contrast, there is concern for harm of BiV pacing, as pacing-induced contraction may place the septum or free wall closer to the LVAD inflow cannula, thereby increasing the risk of suction events and resulting in inefficient LVAD operation, right HF, increased incidence of VAs and overall worsening of symptoms.

In a first prospective randomized study conducted by Chung and coworkers, patients with CF-LVADs with a previously implanted CRT were randomized to either RV pacing or BiV pacing for 1 - to 2-week periods. The group demonstrated that in patients with CF-VADs, a previously implanted CRT device did not provide any additional meaningful haemodynamic and/or clinical benefit. 1 8 Intriguingly, RV pacing was associated with improved functional status, quality of life, fewer ventricular tachyarrhythmias, and more stable lead impedances compared with BiV pacing. Haemodynamic

Remote rhythm monitoring and other telemonitoring devices in left ventricular assist device patients

All current ICDs and implantable loop recorders (ILRs) and most pacemakers can be remotely monitored, and automatically transmit pre-defined alerts without any intervention by the patient. Remote monitoring is currently indicated in ICD patients to reduce inappropriate shocks according to the 2022 ESC guidelines, to manage patients with VAs and to prevent sudden cardiac death. 59 It dramatically reduces time to arrhythmia diagnosis and clinical decisions and reduces the risk of inappropriate shocks by early diagnosis of atrial tachyarrhythmias and technical issues such as lead failure and EMI. 69 However, there are currently no robust data relating to the clinical impact of remote CIED monitoring specifically in the LVAD population.

Sustained VAs may precipitate pump thrombosis and right HF in LVAD patients. 70 In selected patients who are not equipped with a pacemaker or an ICD, it may be useful to use ILRs to monitor for the occurrence of such arrhythmias; there currently are no data on the clinical impact of this strategy.

Prerequisites for effective remote CIED monitoring are similar to non-LVAD patients and thus require ( 1 ) adequate programming of the CIED to detect clinically meaningful events and to transmit alerts to the centre, (2) proper set-up of a home transmitter or cellphone App to communicate with the CIED and to transmit the alerts to the healthcare provider, (3) a work flow for the healthcare provider to evaluate and respond to the alerts in a timely manner, and (4) the patient is readily reachable.

Although current LVADs do not provide remote monitoring capabilities, telemonitoring of parameters (such as power and flow) may be useful to identify pump-related adverse events in a timely manner. 7 1 Other telemonitoring devices could be

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useful in LVAD patients, such as remote haemodynamic pulmonary artery pressure monitoring devices. Safety and feasibility of haemodynamic-guided management with the CardioMEMS sensor in LVAD patients has been reported, 72 but further studies are needed to explore this strategy. Device-based continuous multisensory monitoring with HeartLogic™using a multisensor algorithm in ICD devices by Boston Scientific (Marlborough, MA, USA) to detect impending fluid retention has also been suggested as a potential tool in LVAD patients. 73

Nevertheless, the mean HeartLogic index value increased significantly in the 2 weeks prior to non-HF hospitalizations, largely driven by increases in heart rate and thus may provide useful predictive information for non-HF hospitalizations in these patients, which represent the majority of readmissions in contemporary LVAD cohorts. 74

Cardiac implantable electronic device management in end-of-life left ventricular assist device patients

Focus during end-of-life in LVAD patients should be on the relief of suffering and on preserving the quality of life. How to achieve this varies between patients and the end-of-life scenario. More than $80\%$ of LVAD patients die in a hospital, 75 implying that the majority of LVAD patients die under circumstances with easy access to modification of ICD programming. In LVAD patients with an ICD or CRT-D, timely discussions with patients and their families about programming ICD tachy-therapies off is encouraged, preferably well prior to an end-of-life situation. 76 In unconscious dying patients, turning the ICD therapy for tachyarrhythmia off is always appropriate. While pacing may prolong life in LVAD patients with severe bradyarrhythmia, turning off RV pacing function is not commonly practiced even in end-of-life situations, 77 including LVAD patients.

Shared decision-making

The 202 1 ESC guideline on cardiac pacing and resynchronization highlights the importance of patient-oriented counselling and shared decision-making, however, no evidence-based decision aids tailored to the needs of LVAD patients are currently available. 1 It is essential to consider and discuss conservative and patient-tailored ICD programming with all LVAD patients, particularly when anticipating a CIED battery depletion. Current data do not show any positive impact of ICD on survival of LVAD patients; randomized studies to address this are lacking. 27,78,79 Providing patients with a hand-held magnet and instructions on its use may be appropriate to enhance patient empowerment and to reduce the burden of conscious shocks. Counseling process should be periodic, reflecting the evolving nature of patients’ cardiac status, altered values and competing comorbidities. 80

Areas of uncertainty

• Whether the presence of an ICD or CRT improves the long-term prognosis in patients with LVAD is unclear. • Whether there is any significant clinical or prognostic benefit of an upgrade to CRT in patients supported by LVADs merits further investigation. • Whether any specific subgroups of patients supported by CF-LVADs may benefit from upgrades to ICD and/or CRT therapy remains to be shown. • The efficacy and programming strategies of S-ICD and extravascular ICD in LVAD patients remain to be investigated. • Whether routine inactivation of ICD tachy-therapies is appropriate in patients receiving LVAD and who had no ventricular arrhythmia before LVAD implantation. • The significance of CIED treatment following myocardial recovery and LVAD explant remains to be investigated. • The optimal CIED programming in LVAD patients needs to be identified and validated. • Whether there are any benefits of remote CIED monitoring in patients with LVAD need to be evaluated. • The optimal management strategy in patients with pre-existing CIEDs (leads with long dwell times) and driveline infection is unclear, particularly the risk of CIED extraction. Current data on lead extraction is very limited with short lead dwell times. • Implantation of an ILR may be useful to monitor for sustained VA in LVAD patients who are not CIED carriers, but there are currently no data on the clinical impact of this strategy. • Educational and shared decision-making tools for LVAD patients and their families should be developed, validated, and implemented.

Conflict of interest : O.A.: Advisory board and national or institutional PI for clinical studies: Novartis, Boehringer Ingelheim, AstraZeneca, Merck Sharp & Dohme, Sanofi, Bayer, Pfizer, Amgen, Bristol Myers Squibb, Eli Lilly; medical consults: Restore-Medical, Cordio-Medical, Boehringer Ingelheim. S.A.: honorarium from AstraZeneca for chairmanship in a Greek congress; Abbott is one of the sponsors of the annual advanced heart failure congress in Athens; funds from the European Horizon Program RETENTION (Onassis Cardiac Surgery Center is the coordinating center). H.B.: Abbott, Biotronik, Boston Scientific, Medtronic, Microport: institutional research and fellowship support, speaker and advisory board fees. A.B.G.: lecture and advisory for Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Medtronic, Novartis, Novo Nordisk, Roche Diagnostics, Vifor. C.L.: research contracts: Boston Scientific, Biotronik, Medtronic, Abbot, Microport; personal fees: Medtronic, Biotronik. M.C.: investigator-initiated research grants to institution: Novartis, Abbott, Pfizer; clinical study contracts with institution: Novo Nordisk, CorVia; advisory role, speaker honoraria; travel grants: Abbott, Abiomed, Amgen, Amicus Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Meyers Squibb, GE Healthcare, Krka Pharma, Novartis, NovoNordisk, Pfizer, Pulsify Medical, Roche, Swixx, Takeda, Teva Pharmaceutical Industries, Viatris. A.E.: speaker and consultant fees for Medtronic, Boston Scientific and Abbott. P.P.: honoraria for teaching and proctoring for Biosense Webster, Boston Scientific, Medtronic, Abbott and Biotronik. M.F.: consultant to Medtronic, Boston Scientific and Abbott. A.R.: honoraria for teaching and training from Medtronic, Boston

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Scientific and Phillips; her hospital also receives funding for research fellow from Medtronic. F.G.: consulting fees from Abbott, FineHeart, AdjuCor, Corwave, AstraZeneca, Pfizer, Pharmacosmos, Boehringer Ingelheim, Bayer, Alnylam; speaker’s fee: Novartis. S.R.: consultant for Medtronic, Boston Scientific, Abbott, and Biotronik; member of the Medtronic European CSP Advisory Board and Boston Scientific Strategic Advisory Board. M.P.: personal fees from Abbott Vascular, AstraZeneca, Boehringer Ingelheim, Novartis, Roche Diagnostics and Vifor Pharma. G.R.: TBA. F.R.: no personal payments by pharmaceutical companies or device manufacturers in the last 3 years (remuneration for the time spent in activities, such as participation as steering committee member of clinical trials and member of the Pfizer Research Award selection committee in Switzerland, were made directly to the University of Zurich). The Department of Cardiology (University Hospital Zurich/University of Zurich) reports research, educational and/or travel grants from Abbott, Abiomed, Alnylam, Amarin, Amgen, AstraZeneca, At the Limits, Bayer, Biotronik, BMS, Boehringer Ingelheim, Boston Scientific, Bracco, CM Microport, Concept Medical, CTI, Daiichi Sankyo, Edwards Lifesciences, FomF, Hamilton Health Sciences, IHF, Innosuisse, IumiraDX, Kantar, LabPoint, MedAlliance, Medcon, Medical Education Global Solutions, Medtronic, MicroPort, Monocle, Novartis, Novo Nordisk, OM Pharma, Pfizer, Quintiles, RecorMedical, Roche Diagnostics, Roche Pharma, Sahajanand IN, Sanofi, Sarstedt AG, Servier, Terumo DE, Trama Solutions,V- Wave, Vifor, ZOLL. These grants do not impact on his personal remuneration. J.C.N.: institutional research grants from the Novo Nordisk Foundation and the Danish Heart Foundation outside this work. G.M.C.R.: consulting and Honoria for Anlylamf, Astra Zeneca, Bayer, Boehringer Ingelheim, Cipla, CSL Vifor, Novartis, Medtronic, Servier, Viatris.

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