Leadless Pacemaker Research Articles

Abstract 16763: Complete Heart Block as a Complication of Diffuse Large B Cell Lymphoma

Abbreviations: DLBCL (diffuse large B cell lymphoma), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone). Description of case We present the case of a 78-year-old female who presented initially with a right neck mass, abdominal pain, diarrhea, and recurrent pericardial effusions requiring pericardial window procedure. Biopsy of the neck mass demonstrated a DLBCL. Involvement of a right atrial mass attached to the septum in close relation to the tricuspid valve was seen on TEE. Metastatic disease to the lungs and liver was demonstrated on CT chest and abdomen respectively. The patient posteriorly developed symptomatic bradycardia that on electrocardiogram and telemetry monitoring was shown to be due to a complete heart block with junctional and ventricular escape beats with a rate of 30-40 beats per minute. Due to the anatomical characteristics of the right atrial mass, placement of a right ventricle leadless pacemaker (micra) was decided. The patient was started on mini-CHOP chemotherapy shortly afterwards. Discussion Primary cardiac lymphomas are a rare presentation accounting for less than 1% of all cardiac malignancies. Although rare, secondary involvement of the heart is more frequent than primary involvement and represents 20-25% of the cases. From all the broad subtypes of lymphomas, DLBCL is the most commonly found to affect the cardiac system, often being represented by alterations in the conduction system and causing congestive heart failure. The exact mechanism of the conduction abnormalities in the setting of cardiac lymphoma has not yet been well elucidated but is presumed to be either caused by an infiltration of the conduction system, direct mass burden effect, or a combination of both. It has been seen in similar cases that initiation of chemotherapy can help decrease the pacing requirements or even resolve completely the conduction abnormalities. In a few cases, permanent pacing is required. Metastatic disease to the heart is a marker for poor outcome and median survival with therapy after diagnosis is between 7 to 18 months.

Revisiting predictors of worse atrioventricular valve and left ventricular systolic function following pacemaker therapy.

Predictors of worsening atrioventricular valve regurgitation and left ventricular (LV) systolic function after implantation of a leadless pacemaker (LPM) remain unclear compared with those of a transvenous pacemaker (TPM). We retrospectively analyzed 205 patients who were newly implanted with a permanent pacemaker (119 LPMs and 86 TPMs) and underwent transthoracic echocardiography before and 8±5 months after implantation. We evaluated the worsening of tricuspid and mitral regurgitation (TR and MR), defined as at least one-grade aggravation in severity, and changes in LV ejection fraction (LVEF). Worsening TR occurred more frequently in the LPM group compared to the TPM group (33%vs. 20%, p=.04); however, there was no significant difference between the two groups regarding worsening MR (26%vs. 18%, p=.18) and LVEF change (-2±10%vs. -3±8%, p=.40). In multivariable analysis, independent predictors for worsening TR, MR, and LVEF after implantation were found to be (1) the change from sinus rhythm at baseline to atrioventricular asynchronous right ventricular (RV) pacing (odds ratio [OR]: 5.68, 95% confidence interval [CI]: 1.94-16.70, p<.01); (2) the change from non-pacing ventricular contraction at baseline to RV pacing (OR: 2.42, 95% CI: 1.12-5.24, p=.02); and (3) a higher RV pacing burden (β: -0.05, 95% CI: -0.08--0.02, p<.01), respectively. Worsening TR, MR, and LVEF after pacemaker implantation were not associated with the type of pacing device but loss of atrioventricular synchrony or dependency on RV pacing.

Noncontrast leadless pacemaker implantation under intracardiac echocardiography by the trans-opposite femoral vein approach guide.

Noncontrast leadless pacemaker implantation under intracardiac echocardiography by the trans-opposite femoral vein approach guide.

Gender Differences With Leadless Pacemakers: Periprocedural Complications, Long-Term Device Function, and Clinical Outcomes

Gender Differences With Leadless Pacemakers: Periprocedural Complications, Long-Term Device Function, and Clinical Outcomes

Leadless pacemakers : A"permanently" good solution?

The two currently available leadless pacemakers are highly effective and safe in the respective approval studies and also real-world registries. Compared to conventional pacemakers, there are lower long-term complication rates compared to conventional pacemaker systems (especially regarding lead dislocations and systemic infections). Increasing evidence (currently largely for the Micra™ [Medtronic, Minneapolis, MN, USA] device) shows that these advantages are also valid in the long-term. Leadless pacemakers can therefore be regarded a"permanently good solution", when appropriately implanted in suitable patients.

Spanish pacemaker registry. 20th official report of the Heart Rhythm Association of the Spanish Society of Cardiology (2022)

Introduction and objectivesThis article reports the cardiac pacing activity performed in 2022, including the total number of implants, adherence to remote monitoring, demographic and clinical factors, and the characteristics of the implanted devices. MethodsThe information sources were the CardioDispositivos online platform, the European pacemaker patient identification card, and data provided by the manufacturers. ResultsThe rates of conventional pacemakers and low-energy resynchronizers were 866 and 34 units per million population, respectively. A total of 815 leadless pacemakers were implanted. In all, 16426 procedures performed in 82 hospitals were reported (9407 through CardioDispositivos), representing 40% of the activity. The mean age was 78.6 years, with a predominance of men (60.3%). The most frequent disorder was atrioventricular block, and 14.5% of the patients had atrial fibrillation. There was a predominance of the DDD/R pacing mode (55.6%), and pacing mode was influenced by age, such that more than one-third of patients older than 80 years in sinus rhythm received single-chamber ventricular pacing. The remote monitoring program included 35% of conventional pacemakers and 55% of low-energy resynchronization pacemakers. ConclusionsThe number of conventional pacemakers increased by 5.6%, low-energy resynchronizers by 16%, and leadless pacemakers by 25%. Adherence to remote monitoring was stable. The number of procedures included in CardioDispositivos increased by 11%, although the sample volume decreased. In the coming years, the widespread use of the platform will likely lead to a high-quality registry.

Leadless Pacemaker Implantation, Focusing on Patients With Conduction System Disorders Post–Transcatheter Aortic Valve Replacement: A Retrospective Analysis

BackgroundImpairment of the conduction system is a common complication of transcatheter aortic valve replacement (TAVR), which is typically performed in elderly patients. A leadless pacemaker (LP) may be a suitable option in this frail population, but the available scientific data concerning the efficacy and safety of leadless pacing after TAVR are sparse. The purpose of this analysis was to evaluate the efficacy and safety of LP implantation in patients with relevant bradycardias after TAVR, compared to other indications. MethodsConsecutive patients were retrospectively enrolled. Demographics, background heart diseases, interventional parameters, and follow-up data were collected. ResultsA total of 257 consecutive patients who underwent LP implantation were included. In 26 patients, the device was implanted due to bradycardias after TAVR (TAVR group), whereas the remaining 231 patients were in the population without previous TAVR (non-TAVR group). The mean implantation duration (56 ± 22 minutes in the TAVR group vs 48 ± 20 minutes in the non-TAVR group; P = not significant [NS]) and the implantation success rate (100% in the TAVR group vs 98.7% in the non-TAVR group; P = NS) were similar in the 2 cohorts. No significant differences occurred in pacing parameters (sensing, impedance, and threshold, respectively) between the 2 groups, either at implantation or during follow-up. A total of 8 major periprocedural complications (3.1% of patients in total; 3.8% in the TAVR group vs 3.0% in the non-TAVR group; P = NS) occurred within 30 days, without significant difference between the 2 groups. ConclusionsLP implantation appears to be safe and effective in patients after TAVR, and therefore, this procedure is a suitable option for this often old and frail population.

Racial and Ethnic Disparities in Patients Who Underwent Leadless Pacemaker Implantation

Evidence regarding racial disparities in leadless pacemaker (LP) utilization and outcomes is limited. We aimed to explore ethnicity-based disparities in LP utilization and clinical outcomes of patients who underwent LP implantation. All consecutive patients who underwent LP between January 2019 and January 2023 at our institution were included. Charts were reviewed for baseline characteristics and clinical outcomes. The primary outcomes were procedure-related complications, cardiac rehospitalization, worsening heart failure (HF) or HF hospitalization, and all-cause mortality. All statistical analyses were performed using SPSS Statistics 22 (IBM Corp., Armonk, NY). The p <0.05 was considered statistically significant. A total of 196 adult patients underwent LP implantation during the study period (48% Caucasians, 36.2% Hispanic, 8.2% Asians, and 7.7% African-American). The groups were balanced with respect to baseline demographics, clinical characteristics, and procedure-related complications. During the median follow-up of 104days (interquartile range 24 to 382), no statistically significant differences were observed in worsening HF or HF hospitalization or all-cause mortality among the ethnic groups. After multivariable logistic regression, Asian individuals had higher odds of cardiac readmissions (odds ratio 4.1, 95% confidence interval 1.4 to 12.3, p = 01). Patients from racial and ethnic minorities face significant inequities in arrhythmia care, including patients who have undergone LP implantation. Awareness and a system-based approach (understanding cultural preferences, effective application of evidence-based guidelines, and population-based policies) are crucial to lessen disparities in health care among minorities.

A simultaneous occurrence of pulmonary embolism and cerebral infarction following Micra™ leadless pacemaker implantation.

A simultaneous occurrence of pulmonary embolism and cerebral infarction following Micra™ leadless pacemaker implantation.

The 1st implantation of an atrial only leadless pacemaker in right atrial appendage.

The 1st implantation of an atrial only leadless pacemaker in right atrial appendage.

Retrieval of Chronically Implanted Dual-chamber Leadless Pacemakers in an Ovine Model.

The clinical utilization of leadless pacemakers (LPs) as an alternative to traditional transvenous pacemakers is likely to increase with the advent of dual-chamber LP systems. Since device retrieval to allow LP upgrade or replacement will become an important capability, the first such dual-chamber, helix-fixation LP system (Aveir DR; Abbott, Abbott Park, IL) was specifically designed to allow catheter-based retrieval. In this study, the preclinical performance and safety of retrieving chronically implanted dual-chamber LPs was evaluated. Atrial and ventricular LPs were implanted in the right atrial appendage and right ventricular apex of 9 healthy ovine subjects. After ≈2 years, the LPs were retrieved using a dedicated transvenous retrieval catheter (Aveir Retrieval Catheter; Abbott) by snaring, docking, and unscrewing from the myocardium. Comprehensive necropsy/histopathology studies were conducted to evaluate device- and procedure-related outcomes. At a median of 1.9 years postimplant (range, 1.8-2.6), all 18 of 18 (100%) LPs were retrieved from 9 ovine subjects without complications. The median retrieval procedure duration for both LPs, from first-catheter-in to last-catheter-out, was 13.3 minutes (range, 2.5-36.4). Postretrieval, all right atrial, and right ventricular implant sites demonstrated minimal tissue disruption, with intact fibrous tissue limited to the distal device body. No significant device-related trauma, perforation, pericardial effusion, right heart or tricuspid valve injury, or chronic pulmonary thromboembolism were observed at necropsy. This preclinical study demonstrated the safe and effective retrieval of chronically implanted, helix-fixation, dual-chamber LP systems, paving the way for clinical studies of LP retrieval.

Outcomes of patients implanted with an atrioventricular synchronous leadless ventricular pacemaker in the Medicare population

BackgroundThe Micra AV Coverage with Evidence Development (CED) study is a novel analysis of utilization and outcomes associated with Micra AV leadless pacing among US Medicare patients. ObjectiveTo describe patient characteristics, complications, and outcomes of patients implanted with a Micra AV leadless pacemaker compared to a contemporaneous cohort of dual chamber transvenous pacemaker patients. MethodsPatients implanted with Micra AV (N=7,471) or a dual chamber transvenous pacemaker (N=107,800) from February 5, 2020 - December 1, 2021 were identified using device registry-linked Medicare claims data. Acute complications were assessed at 30 days and chronic complications, reinterventions, and all-cause mortality were assessed at 6 months. ResultsMicra AV patients had higher rates of end-stage renal disease (14.9% vs. 2.0%, P<0.0001) and overall comorbidity burden (mean Charlson Comorbidity Index 4.9 vs. 3.8, P<0.0001). There was no difference in the unadjusted rate of complications at 30 days (9.1% vs. 8.7%, P=0.61), and Micra AV patients had a significantly lower adjusted rate of complications (8.6% vs. 11.0%, P<0.0001). At 6 months, Micra AV patients had significantly lower rates of complications (adj. HR 0.50, 95% CI 0.43-0.57, P<0.0001) and reinterventions (adj. HR 0.46, 95% CI 0.36-0.58, P<0.0001). Micra AV patients had higher all-cause mortality at 30 days and 6 months, likely due to differences in underlying risk for mortality. ConclusionPatients implanted with Micra AV had similar rates of complications at 30 days and significantly lower rates of complications and reintervention at 6 months, despite being sicker than patients implanted with a transvenous pacemaker.

Outcomes of leadless pacemaker implantation after cardiac surgery and transcatheter structural valve interventions.

Permanent pacing indications are common after cardiac surgery and transcatheter structural valve interventions. Leadless pacemakers (LPs) have emerged as a useful alternative to transvenous pacemakers. However, current commercially available LPs are unable to provide atrial pacing or cardiac resynchronization and relatively little is known about LP outcomes after cardiac surgery and transcatheter valve interventions. This retrospective study included patients who received a Micra VR (MicraTM MC1VR01) or Micra AV (MicraTM MC1AVR1) (Medtronic) leadless pacemaker following cardiac surgery or transcatheter structural valve intervention between September 2014 and September 2022. Device performance and clinical outcomes, including ventricular pacing burden, ejection fraction, and need for conversion to transvenous pacing systems, were evaluated during follow-up. A total of 78 patients were included, of whom 40 received a Micra VR LP implant, and 38 received a Micra AV LP implant. The mean age of the cohort was 65.9 ± 17.9 years, and 48.1% were females. The follow-up duration for the entire cohort was 1.3 ± 1.1 years: 1.6 ± 1.3 years for the Micra VR group and 0.8 ± 0.5 years for the Micra AV group. Among the cohort, 50 patients had undergone cardiac surgery and 28 underwent transcatheter structural valve interventions. Device electrical performance was excellent during follow-up, with a small but clinically insignificant increase in ventricular pacing threshold and a slight decrease in pacing impedance. The mean right ventricle pacing (RVP) burden significantly decreased over time in the entire cohort (74.3% ± 37.2% postprocedure vs. 47.7% ± 40.6% at last follow-up, p < .001), and left ventricle ejection fraction (LVEF) showed a modest but significant downward trend during follow-up (55.0% ± 10.6% vs. 51.5% ± 11.2% p < .001). Patients with Micra VR implants had significantly reduced LVEF during follow-up (54.1% ± 11.9% vs. 48.8% ± 11.9%, p = .003), whereas LVEF appeared stable in the Micra AV group during follow-up (56.1% ± 9.0% vs. 54.6% ± 9.7%, p = .06). Six patients (7.7%) required conversion to transvenous pacing systems, four who required cardiac resynchronization for drop in LVEF with high RVP burden and two who required dual-chamber pacemakers for symptomatic sinus node dysfunction. Leadless pacemakers provide a useful alternative to transvenous pacemakers in appropriately selected patients after cardiac surgery and transcatheter structural valve interventions. Device performance is excellent over medium-term follow-up. However, a significant minority of patients require conversion to transvenous pacing systems for cardiac resynchronization or atrial pacing support, demonstrating the need for close electrophysiologic follow-up in this cohort.

Novel approaches for leadless pacemaker implantation in the extra-cardiac Fontan cohort: Options to avoid leaded systems or epicardial pacing.

Fontan surgery, a palliative procedure for single ventricle patients, often leads to the need for permanent pacing. Epicardial pacing has limitations, while transvenous pacing carries risks in the Fontan circulation. This case series introduces a novel approach of leadless pacemaker implantation in the extra-cardiac Fontan (ECF) cohort to overcome these limitations. The study includes four cases of leadless pacemaker (Micra™) implantation in patients with ECF. Procedures were performed under general anesthesia with guidance from trans-esophageal echocardiography. Various access routes were used, including trans-carotid and trans-fenestration approaches. Procedural details, parameters, and follow-up data were collected. All leadless pacemaker implantations were successful, with satisfactory electrical parameters and stable pacing postprocedural outcomes during short-term follow-up. One patient required closure of their fenestration for symptomatic desaturation post procedurally. Leadless pacemaker implantation via trans-carotid and trans-fenestration approaches appears to be a feasible back up option for pacing in Fontan patients where other options have been exhausted or there is a patient choice to avoid surgery. These techniques provide an option to avoid leaded systems or epicardial pacing, reducing the need for multiple thoracotomies and addressing challenges associated with surgical pacing leads. Further studies are needed to evaluate long-term outcomes and assess the broader application of leadless pacemakers in the Fontan population.

Association of leadless pacing with ventricular and valvular function.

Traditional transvenous pacemakers are associated with worsening tricuspid valve function due to lead-related leaflet impingement, as well as ventricular dysfunction related to electromechanical dyssynchrony from chronic right ventricular (RV) pacing. The association of leadless pacing with ventricular and valvular function has not been well established. We aimed to assess the association of leadless pacemaker placement with changes in valvular regurgitation and ventricular function. Echocardiographic features before and after leadless pacemaker implant were analyzed in consecutive patients who received a leadless pacemaker with pre- and postprocedure echocardiography at Duke University Hospital between November 2014 and November 2019. Valvular regurgitation was graded ordinally from 0 (none) to 3 (severe). Among 54 patients, the mean age was mean age was 70.1 ± 14.3 years, 24 (44%) were women, and the most frequent primary pacing indication was complete heart block in 24 (44%). The median RV pacing burden was 45.4 (interquartile range [IQR] 3.5-97.0). On echocardiogram performed 8.9 months (IQR 4.5-14.5) after implant, there was no change in the average severity of tricuspid regurgitation (mean change 0.07 ± 1.15, p = .64) from pre-procedure echocardiogram. We observed a decrease in the average left ventricular ejection fraction (LVEF) (52.3 ± 9.3 to 47.9 ± 12.1, p = .0019) and tricuspid annular plane systolic excursion (TAPSE) (1.8 ± 0.6 to 1.6 ± 0.4, p = .0437). Thirteen patients (24%) had absolute drop in LVEF of ≥10%. We did not observe short term worsening valvular function in patients with leadless pacemakers. However, consistent with the pathophysiologic impact of RV pacing, leadless pacing was associated with a reduction in biventricular function.

Comparison of Safety of Leadless Pacemakers and Transvenous Pacemakers: A Meta-Analysis.

Pacemakers have been accessible for six decades, and clearly defined criteria for pacemaker implantation have been established. Within the contemporary clinical practice, two dependable pacing platforms exist leadless pacemakers and transvenous pacemakers. The aim of this meta-analysis is to compare the safety of leadless pacemakers to transvenous pacemakers.This meta-analysis adhered to the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 framework.A comprehensive and systematic search was conducted across various databases including Scopus, Cochrane Library, and EMBASE, spanning from inception to August 15, 2023.The primary outcomes assessed in this meta-analysis were total complications, all-cause mortality, and device-related complications. Furthermore, secondary outcomes evaluated encompassed the need for reintervention, occurrences of pneumothorax, pericardial effusion, endocarditis, hemothorax, and hematoma. Total 17 studies were included in this meta-analysis. The findings of this study showed that patients with leadless pacemakers had a lower risk of total complications, device-related complications, pneumothorax, and endocarditis. The risk of reintervention was significantly lower in the leadless pacemaker group. However, compared to a transvenous pacemaker, the risk of pericardial effusion was significantly higher in the leadless pacemaker group.It is important to acknowledge the limitations arising from the lack of extensive long-term follow-up data for leadless pacemakers. As technology evolves, continued research will be essential in uncovering the full spectrum of prolonged complications associated with these devices.

Acute pacing threshold elevation during simultaneous Micra leadless pacemaker implantation and AV node ablation: Clinical cases, computer model and practical recommendations.

In patients with refractory atrial fibrillation (AF), atrioventricular nodal (AVN) ablation and permanent pacemaker implantation is recommended. The Micra Transcatheter Pacing System (Micra) is a single chamber leadless pacemaker (LPM) and thus offers the possibility of AV node (AVN) ablation in the same procedure. Pacing threshold (PT) elevation after radiofrequency (RF) ablation is a potential complication. We conducted a single center retrospective cohort study. Patients implanted with a Micra (n = 84) and concomitant or delayed AVN ablation (n = 12) from 2014 to 2022 were included. Two cases of acute Micra PT elevation immediately following RF AVN ablation required device retrieval and implantation of a new Micra. Procedural characteristics and electrophysiological parameters were analyzed, and a computer model was performed to determine factors responsible for acute PT elevations. A total of 84 patients were included. Mean age was 74±10 and 48% were women. Twelve patients (14%) underwent AVN ablation. Two patients had acute PT elevation requiring device retrieval despite no direct contact of the ablation catheter with the Micra. Computer modeling shows that significant dissipated power due to electrical field coupling can occur at the tip or ring electrode if the catheter is not kept at a safe distance (≥35mm) from the Micra when a maximum power of 100W is delivered. Concurrent AVN ablation and Micra implantation is safe in most patients. To prevent acute PT elevation, keeping a safe distance of ≥35mm from the tip and ring electrodes of the Micra and using lower power output may prevent this complication.

Quality and transparency of evidence for implantable cardiovascular medical devices assessed by the CORE-MD consortium.

The European Union Medical Device Regulation 2017/745 challenges key stakeholders to follow transparent and rigorous approaches to the clinical evaluation of medical devices. The purpose of this study is a systematic evaluation of published clinical evidence underlying selected high-risk cardiovascular medical devices before and after market access in the European Union (CE-marking) between 2000 and 2021. Pre-specified strategies were applied to identify published studies of prospective design evaluating 71 high-risk cardiovascular devices in seven different classes (bioresorbable coronary scaffolds, left atrial appendage occlusion devices, transcatheter aortic valve implantation systems, transcatheter mitral valve repair/replacement systems, surgical aortic and mitral heart valves, leadless pacemakers, subcutaneous implantable cardioverter-defibrillator). The search time span covered 20 years (2000-21). Details of study design, patient population, intervention(s), and primary outcome(s) were summarized and assessed with respect to timing of the corresponding CE-mark approval. At least one prospective clinical trial was identified for 70% (50/71) of the pre-specified devices. Overall, 473 reports of 308 prospectively designed studies (enrolling 97 886 individuals) were deemed eligible, including 81% (251/308) prospective non-randomized clinical trials (66 186 individuals) and 19% (57/308) randomized clinical trials (31 700 individuals). Pre-registration of the study protocol was available in 49% (150/308) studies, and 16% (48/308) had a peer-reviewed publicly available protocol. Device-related adverse events were evaluated in 82% (253/308) of studies. An outcome adjudication process was reported in 39% (120/308) of the studies. Sample size was larger for randomized in comparison to non-randomized trials (median of 304 vs. 100 individuals, P < .001). No randomized clinical trial published before CE-mark approval for any of the devices was identified. Non-randomized clinical trials were predominantly published after the corresponding CE-mark approval of the device under evaluation (89%, 224/251). Sample sizes were smaller for studies published before (median of 31 individuals) than after (median of 135 individuals) CE-mark approval (P < .001). Clinical trials with larger sample sizes (>50 individuals) and those with longer recruitment periods were more likely to be published after CE-mark approval, and were more frequent during the period 2016-21. The quantity and quality of publicly available data from prospective clinical investigations across selected categories of cardiovascular devices, before and after CE approval during the period 2000-21, were deemed insufficient. The majority of studies was non-randomized, with increased risk of bias, and performed in small populations without provision of power calculations, and none of the reviewed devices had randomized trial results published prior to CE-mark certification.

Simultaneous procedure transcatheter mitral valve repair and leadless pacemaker implantation under transesophageal echocardiography.

When we implant leadless pacemaker in patients with contrast agent allergy or poor renal function, the use of sufficient contrast agent is hesitant. Aided by imaging assessment (e.g., intracardiac echocardiography), the procedure may be feasible with a small amount of contrast medium or no contrast medium. In this case, leadless pacemaker implantation was performed at the same time as the transcatheter mitral valve repair, and leadless pacemaker implantation was successful with the use of a very small amount of contrast medium under transesophageal echocardiography guidance.

Leadless Pacemakers: Current Achievements and Future Perspectives.

Despite the technological advances in pacemaker technology, the transvenous implanted leads are still considered the Achilles' heel of this rhythm-control therapy. The leadless permanent pacemaker system was developed as an option to bypass the weakness of the transvenous approach. Advances in battery technology and deep miniaturisation of electronics now offer the opportunity to implant the whole pacemaker system into the right ventricle. This review aims to provide a comprehensive report on the advent of leadless pacemakers, their clinical usefulness and the future perspectives of this disruptive and promising technology. Further research is required before some of these technologies are safely and routinely used in clinical practice.