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Cardiovascular implantable electronic devices (CIEDs) are essential management options for patients with brady- and tachyarrhythmias or heart failure with concomitant optimal pharmacotherapy. Despite increasing technological advances, there are still gaps in the management of CIED patients, eg, the growing number of lead- and pocket-related long-term complications, including cardiac device–related infective endocarditis, requires the greatest care. Likewise, patients with CIEDs should be monitored remotely as a part of a comprehensive, holistic management approach. In addition, novel technologies used in smartwatches may be a convenient tool for long-term atrial fibrillation (AF) screening, especially in high-risk populations. Early detection of AF may reduce the risk of stroke and other AF-related complications. The objective of this review article was to provide an overview of novel technologies in cardiac rhythm–management devices and future challenges related to CIEDs.
Keywords: cardiovascular implantable electronic devices, CIEDs, pacemaker, implantable cardioverter–defibrillator, cardiac resynchronization therapy, remote monitoring, wearable technology
Modern cardiology develops and progresses through innovations in technology and a deeper understanding of the pathophysiology of heart diseases. Indeed, marked advances have been made since 1958, when the first pacemaker was implanted.1 Over the decades, cardiovascular implantable electronic devices (CIEDs) have become the cornerstone of management for patients with brady- or tachyarrhythmias and heart failure (HF) with reduced ejection fraction (EF).2–5 This is associated with the emergence of complex stimulation systems — pacemakers (PMs), implantable cardioverter–defibrillators (ICDs), cardiac resynchronization therapy (CRT) — and the growing number of patients with different indications treated with CIEDs. Indeed, rhythm-management devices may improve the life expectancy and quality of life of these patients.1
Impressive progress in the field of cardiac pacing has led to technical improvements in existing devices and leads, and new ones are constantly emerging. Despite this development, the systems may have a downside associated with early and late (>3 months after implantation) complications of using such CIEDs. Many are related to the weakest links, ie, the transvenous lead and subcutaneous pocket.6,7 Wireless technology and optimization of pacing systems have emerged to minimize potential CIED side effects. The effective interrogation and monitoring of patients with CIEDs to detect arrhythmias or system malfunction assumes even great importance.8 The objective of this review article was to provide an overview of novel technologies in cardiac rhythm–management devices and future directions and challenges related to CIEDs.
We performed a comprehensive literature search using electronic databases (PubMed, ClinicalTrials.gov) to identify relevant studies and systematic reviews reporting on cardiac rhythm–management devices. The following search terms were included (individually and in combination): cardiac implantable electronic devices, pacemaker, implantable cardioverter–defibrillator, cardiac resynchronization therapy, leadless cardiac pacemaker, wearable cardioverter–defibrillator, subcutaneous cardioverter–defibrillator, substernal lead, remote monitoring, atrial high-rate episodes, smartwatch, and wearable technology. Selected articles, clinical trials, and guideline documents were reviewed for inclusion.
A challenge is whether a patient appropriately qualifies for CIED implantation, despite the current guidelines.2–5 SCD-HeFT9 was a randomized controlled trial (RCT) conducted among 2,521 patients with HF, left ventricular EF (LVEF) ≤35%, and New York Heart Association class II or III. It was found that ICD therapy was related to a 23% reduction of mortality compared with patients treated with amiodarone or placebo.9 However, the recent results from the DANISH trial10 did not show a survival benefits among patients with nonischemic HF with ICD implanted as primary prevention of sudden cardiac death (SCD). The exception was the subgroup of patients aged
Beyond recommendations about ICD therapy in patients with ischemic cardiomyopathy and poor LVEF, diagnostic algorithms for the identification of patients with relatively preserved LV contractility at increased risk of major arrhythmic events have been proposed. The PRESERVE EF study12 was performed among 575 patients of mean age 57 years and LVEF 50.8%. Participants were assessed in two steps: if there were abnormalities on ECG (eg, premature ventricular complexes, unsustained ventricular tachycardia, late potentials, prolonged QTc), patients were referred to programmed ventricular stimulation (PVS). For those with induced ventricular tachyarrhythmia (VT), ICDs were implanted. The primary end point was the occurrence of a major arrhythmic event: sustained ventricular tachycardia/fibrillation, appropriate ICD therapy, or SCD. The study found that 35.5% had abnormal ECG findings, and 27% of those were inducible with PVS. ICDs were implanted in 37 patients (90.2% of inducible subgroup). During the 32-month follow-up, there were no SCDs among ICD patients, whereas nine appropriate ICD shocks were observed. A previous study13 showed that patients with hypertrophic cardiomyopathy and noninducible arrhythmia with PVS had longer event-free survival. Inducibility with PVS was an independent predictor of SCD or appropriate ICD therapy among patients with hypertrophic cardiomyopathy.13
While the effectiveness of ICD therapy in patients with nonischemic dilated cardiomyopathy and reduced LVEF (≤35%) is debated, the selection of patients with dilated cardiomyopathy and well-maintained LV contractility (LVEF >35%) at risk of malignant cardiac arrhythmic events who may gain a survival benefit from ICD therapy represents another challenging area. Gatzoulis et al14 used a two-step algorithm in another study — ReCONSIDER; (NCT04246450) — which is an ongoing prospective observational trial among patients with nonischemic cardiomyopathy aiming to recognize those with a truly high risk of SCD.14 CMR GUIDE (NCT01918215)15 is an ongoing RCT to assess myocardial fibrosis and related risk of SCD among patients with LVEF 36%–50% and evidence of fibrosis on optimal HF therapy. Patients are randomized to receive ICD (as primary SCD prevention) or an implantable loop recorder (ILR). The composite primary end point is time to SCD or hemodynamically significant VT.15
Another debated issue is the optimal selection criteria for CRT responders, especially among patients with HF, without typical left bundle–branch block.16 New strategies, such as leadless pacing, optimization of LV-lead position, multipolar LV pacing, alternative right ventricular (RV) pacing, eg, His-bundle pacing or cardiac contractility modulation, may positively impact on further CIED therapy.17 MORE-CRT MPP-PHASE II (NCT02006069)18 is an RCT to assess the impact of multipoint pacing in nonresponders to 6 months of standard biventricular pacing. Preferential LV-only pacing is also considered an alternative to standard biventricular pacing.19 A prospective randomized study of CRT with preferential adaptive LV-only pacing (AdaptResponse, NCT02205359)20 is assessing if the new pacing algorithm reduces the incidence of the combined end point of all-cause mortality and HF decompensation compared with conventional CRT among patients eligible for CRT. The AdaptivCRT algorithm optimizes the pacing method and atrioventricular/interventricular delays, based on the current patient’s activity and intrinsic conduction.20
His-bundle pacing is the most physiological form of ventricular pacing, and appears to be a safe and effective method during long-term follow-up.21 This approach is considered superior to standard RV pacing and may also improve clinical outcomes in patients with CRT indications.22 The His-SYNC (NCT02700425)23 pilot trial was the first RCT comparing His-bundle pacing for CRT (His-CRT) vs biventricular pacing (BiV-CRT) among 41 patients with standard indications for CRT. At 6-month follow-up, His-CRT resulted in QRS narrowing with a nonsignificant trend toward a higher rate of echocardiographic response (91% vs 54%, p=0.078) compared with BiV-CRT; however, there were no significant differences in mortality or cardiovascular hospitalization between the groups.23 As such, large multicenter RCTs are necessary to evaluate the clinical efficacy of His-bundle pacing and also comparing His-CRT and BiV-CRT. It is also open whether patients who qualify for CRT have a survival benefit from ICD. RESET-CRT (NCT03494933) is an ongoing RCT to compare clinical outcomes among patients with a CRT PM vs CRT defibrillator.
A recent European Heart Rhythm Association (EHRA) consensus document on management of arrhythmias and cardiac electronic devices in critically ill and postsurgery patients highlighted the risks and challenges among CIED patients with a terminal illness.24 In an EHRA survey,25 73% of patients declared that CIED implantation improved their quality of life, whereas 36% had concerns about the device, mostly related to ICD shocks, daily activities, or impairment of the device. Indeed, the final decision about CIED implantation should take into account the patient’s age, frailty, cardiac condition, and other comorbidities, concomitant with personal values and preferences.
Therefore, it is often necessary to create novel algorithms for the selection of CRT responders, individualized risk scores for SCD, or procedure-related complications, which may result in a highly individualized approach and targeted CIED implantation. The future may bring patient-specific digital models to calculate the risk–benefit profile and create a simulation — virtual implantation. This might check whether the procedure is feasible and which device is favorable for each patient, but also guide a lead during the real procedure. In addition, CIEDs may be considered a cotreatment of other morbidities, such as hypertension.NCT03757377 is an ongoing RCT evaluating a new PM algorithm that may be useful for patients with indications for antibradycardia pacing and persistent hypertension despite pharmacotherapy.
Transvenous leads represent a major source of CIED complications — not only dislocation or mechanical damage but also tricuspid regurgitation, venous occlusion, superior vena cava syndrome, cardiac perforation, cardiac device–related infective endocarditis (CDRIE) — and subcutaneous pockets: hematoma, decubitus, inflammation.6,7,26 Palmisano et al27 reported a higher risk of all-cause death among patients with CIEDs and early complications — pneumothorax (HR 8.731, 95% CI 1.42–53.63) and pocket hematoma (HR 2.515, 95% CI 1.07–5.94) — whereas CDRIE was most markedly related to increased risk of cardiovascular death (HR 4.025, 95% CI 1.5–10.78) during median follow-up of 56.9 months. An EHRA international consensus on how to prevent, diagnose, and treat CIED-infections28 states that prevention and careful consideration before implantation are the best treatment for CDRIE. Indeed, leadless cardiac PMs (LCPs) and extravascular cardioverter-defibrillators have been designed to minimize complications. Also, an absorbable, antibiotic-eluting envelope has been created to use with CIEDs as a prophylactic strategy to prevent CDRIE.29 These new technologies have already found a place in everyday clinical practice.
An LCP is a small (volume 0.8 cm 3 ) single-chamber PM that is implanted directly into the RV by a special catheter and introducer sheath via transfemoral access.30 Therefore, it does not require the subcutaneous pocket or transvenous lead.31 The first LCP was Nanostim (St Jude Medical), implanted worldwide between 2013 and 2016. The device was recalled in 2016, due to battery failures, but the concept of LCPs has been widely accepted.32
At present, the only type of LCP available on the market is the Micra transcatheter pacing system. The pacing mode is similar to transvenous PMs, so an LCP may be used as an alternative device.30,33 However, the system is limited to the RV component, meaning that an LCP may be indicated only for patients requiring single-chamber pacing, eg, permanent atrial fibrillation (AF) with bradycardia or for those with low expected stimulation percentage.30 As such, patients with missing or difficult venous access, with a history of CDRIE, and indications for ventricular single-chamber pacing are considered good LCP candidates. Importantly, the potential benefits of LCPs must be confronted with the limited data on the long-term follow-up, and also the procedure of device replacement or retrieval is still debated.34 According to a national expert consensus document of the Austrian Society of Cardiology, LCP retrieval should not be recommended as a routine procedure and should be limited only to specific issues, ie, endocarditis or system upgrades.34 One worldwide experience of 40 successful device retrievals revealed that it may be feasible and safe if performed with a special sheath and a snare catheter and introduced via femoral access. The most common reasons for extraction included elevated pacing threshold, endovascular infection, and indications for a system upgrade to a transvenous device.35 If it is necessary to replace the battery, a new LCP may be implanted next to old devices without extraction of previous ones; however, current clinical experience is very limited.34
The results of the Micra Transcatheter Pacing Study36 showed the safety and efficacy(primary safety and efficacy end points were reached in 96% and 98.3%, respectively) of LCPs among 725 patients who had undergone device implantation. Likewise, the Micra Post-Approval Registry37 reported a high rate of successful LCP implantations (99.1%) with a low risk of major complications (2.7%) among 1,817 patients. During follow-up of 12-months postprocedure, complication rates in LCP patients were significantly lower (HR 0.37, 95% CI 0.27–0.52) than a historical transvenous PM group. The most common complications in the LCP group were pacing issues (0.72%), groin injury (0.61%), cardiac effusion/perfusion (0.44%), and infection (0.17%).37 In another study, El-Chami et al38 reported on the safety and feasibility of LCPs, also in patients after PM extraction and a recent CDRIE.
Piccini et al39 compared clinical outcomes among 720 patients successfully implanted with LCPs, based on ventricular pacing indications: individuals with AF (68.3%) and those without AF (31.7%). Reasons for selecting LCPs in the non-AF group included an expectation of infrequent pacing (66.2%) and advanced age (27.2%). During 24 months of follow-up, there were no significant differences between the groups in occurrence of the composite primary outcome (cardiac failure, PM syndrome, or LCP-related syncope).39 In another study, the safety and mortality of LCP implantation was assessed and stratified by whether patients were precluded from transvenous PMs.40 It was found that 19.4% of patients were ineligible for traditional PMs because of venous access issues or prior CDRIE. Both acute and total mortality at 36 months (2.75% vs 1.32% [p=0.022] and 38.1% vs 20.6% [p
Despite concerns regarding LCPs in frail elderly patients, because of implant-sheath size and risk of perforation, Micra implantation also appears to be safe and feasible among those individuals.41,42 However, RCTs directly comparing the efficacy and safety of LCPs vs transvenous PMs are needed. In the EHRA prospective survey,43 the overall use of LCPs in daily clinical practice remains low, constituting only 9% of all procedures and 36% of single-chamber PM implants. LCPrecipients were more often male (74% vs 54%) and had a history of valvular heart disease (45% vs 35%), AF (65% vs 23%), and other comorbidities (66% vs 52%) than those with transvenous single-chamber PMs, but no significant association was observed with patients’ age.43 LCP implantation was successful in 98% of recipients, and the only procedure-related complication was groin hematoma.44 Indeed, leadless devices are still in development, and there are also the prototypes of dual-chamber systems,45 which may be used in a wider group of patients. As such, LCPs are a potential game changer for modern CIEDs.
MARVEL (NCT03157297)46 was a recent study of a new LCP algorithm to synchronize ventricle pacing with atrial sensing (synchronous atrioventricular [AV] pacing). Consequently, MARVEL 2 (NCT03752151)47 revealed that the new algorithm provided successful AV-synchrony pacing (mean 89.2%) among 75 LCP recipients with sinus rhythm and AV block. Notably, the atrial sensing algorithms were safe, and there were neither pauses nor episodes of PM-mediated tachycardia.47 The technology is currently used in a new Micra AV device (approved by the US Food and Drug Administration in January 2020), broadening potential indications to LCP implantation.48 Further innovations, such as compatibility with extravascular ICDs, leadless CRT, renewable batteries, or less invasive implantation procedures, are highly anticipated.
The SELECT-LV study49 investigated the clinical efficacy and safety of wireless stimulation endocardially for CRT (WiSE-CRT) pacing via an LV endocardial electrode and a pulse generator (implanted subcutaneously). The trial was conducted among 35 patients with HF and indications for biventricular pacing who were nonresponders to traditional CRT or implantation of a coronary sinus lead was not possible. The feasibility and efficacy of WiSE-CRT were reported. Rates of successful implantation and effective CRT pacing were high (97.1%), with a substantial improvement (84.8%) in the clinical composite score at 6 months; however, the rate of early serious complications was 31.5% at 1-month postprocedure follow-up (8.6% within 24 hours and 22.9% between 24 hours and 1 month).49 According to recent data from a Multicenter International Registry of the WiSE-CRT pacing system,50 implantation of the device was feasible in 94.4% of patients and 70% of those reported improvement in of HF symptoms. Complication rates differed among the centers: 4.4%, 18.8%, and 6.7% within
Subcutaneous cardioverter-defibrillators (sICDs) are implantable devices comprising a subcutaneous pulse generator and subcutaneous lead to deliver a shock as VT therapy. According to the current ESC guidelines, sICDs may be an alternative for patients who require an ICD but do not have an indication for ventricular pacing, CRT, or antitachycardia pacing.5 The American Heart Association guidelines4 recommend sICDs for patients without proper venous access or at high risk of CDRIE. Boersma et al56 reported low periprocedural complication rates, with 99.6% successfully implanted devices and high defibrillation efficacy (99.2% during defibrillation testing) among 1,116 patients who had undergone sICD implantation as primary prevention of SCD. In another study, Boersma et al57 indicated a low risk of infection in sICD recipients, even in individuals with a history of CDRIE and explanted transvenous ICDs.
Results from an EHRA prospective survey on sICD use showed that sICDs were favorable among younger patients and those with lead-related complications or elevated risk/history of CDRIE, taking into consideration patient preferences and active lifestyle. Of note, need for ventricular antitachycardia pacing, CRT, or permanent pacing were benefiting, the transvenous ICD.58 Implantation time and periprocedural complication rates were similar in both subgroups.59 Since 2010, when sICD became available for patients, this technology has been evolving.60 Various ongoing clinical trials have been designed to assess new extravascular systems, eg, EV ICD (NCT04060680) and ASE (NCT03802110), for testing new shock configurations.
ASD261 was the first human study to evaluate a novel approach to ICD therapy — substernal leads. Pacing threshold, sensing, and defibrillation efficacy were assessed among 79 patients who had undergone lead implantation. The lead was placed into the substernal space via subxiphoid access, and a defibrillation-patch electrode or active can emulator (subcutaneous) was set in the left mid-axillary line. It was found that R-wave amplitudes were compliant with ICD sensing (median R-wave 2.4 mV), successful ventricular pacing rates were 97.4%, and defibrillation efficacy was >80% with a single shock of 30 J. The lower shock energy (compared with the sICD’s 80 J) may be beneficial for battery longevity.61 Indeed, substernal lead therapy may be feasible, and results are promising. Nevertheless, neither long-term follow-up data nor risk of infection and lead extraction are available. Indeed, substernal lead therapy may be feasible, and results are promising. Nevertheless, neither long-term follow-up data nor risk of infection and lead extraction are available ( Table 1 ).
Comparison of Implantable Cardioverter Defibrillators
| Transvenous ICD | Subcutaneous ICD | Substernal Lead | |
|---|---|---|---|
| Intracardiac lead | + | – | – |
| Ventricular pacing | + | – | + |
| Antitachycardia pacing | + | – | + |
| Defibrillation efficacy | + | + | + |
| Shock energy | 40 J | 80 J | 40 J |
| Implantation procedure | Feasible | Feasible | Feasible |
| Periprocedural complication rates | 4% | 4% | Unknown |
| Risk of infection | 8.9/1,000 device-years | Low | Unknown |