The Properties of the Transient Outward, Inward Rectifier and Acetylcholine-Sensitive Potassium Currents in Atrial Myocytes from Dogs in Sinus Rhythm and Experimentally Induced Atrial Fibrillation Dog Models.

AIMS: Atrial fibrillation (AF) is the most common chronic/recurrent arrhythmia, which significantly impairs quality of life and increases cardiovascular morbidity and mortality. Therefore, the aim of the present study was to investigate the properties of three repolarizing potassium currents which were shown to contribute to AF-induced electrical remodeling, i.e., the transient outward (Ito), inward rectifier (IK1) and acetylcholine-sensitive (IK,ACh) potassium currents in isolated atrial myocytes obtained from dogs either with sinus rhythm (SR) or following chronic atrial tachypacing (400/min)-induced AF. METHODS: Atrial remodeling and AF were induced by chronic (4-6 weeks of) right atrial tachypacing (400/min) in dogs. Transmembrane ionic currents were measured by applying the whole-cell patch-clamp technique at 37 °C. RESULTS: The Ito current was slightly downregulated in AF cells when compared with that recorded in SR cells. This downregulation was also associated with slowed inactivation kinetics. The IK1 current was found to be larger in AF cells; however, this upregulation was not statistically significant in the voltage range corresponding with atrial action potential (-80 mV to 0 mV). IK,ACh was activated by the cholinergic agonist carbachol (CCh; 2 µM). In SR, CCh activated a large current either in inward or outward directions. The selective IK,ACh inhibitor tertiapin (10 nM) blocked the outward CCh-induced current by 61%. In atrial cardiomyocytes isolated from dogs with AF, the presence of a constitutively active IK,ACh was observed, blocked by 59% with 10 nM tertiapin. However, in "AF atrial myocytes", CCh activated an additional, significant ligand-dependent and tertiapin-sensitive IK,ACh current. CONCLUSIONS: In our dog AF model, Ito unlike in humans was downregulated only in a slight manner. Due to its slow inactivation kinetics, it seems that Ito may play a more significant role in atrial repolarization than in ventricular working muscle myocytes. The presence of the constitutively active IK,ACh in atrial myocytes from AF dogs shows that electrical remodeling truly developed in this model. The IK,ACh current (both ligand-dependent and constitutively active) seems to play a significant role in canine atrial electrical remodeling and may be a promising atrial selective drug target for suppressing AF.

Risk of Cardiac Implantable Electronic Device Infection after Early versus Delayed Lead Repositioning.

(1) Background: Early reintervention increases the risk of infection of cardiac implantable electronic devices (CIEDs). Some operators therefore delay lead repositioning in the case of dislocation by weeks; however, there is no evidence to support this practice. The aim of our study was to evaluate the impact of the timing of reoperation on infection risk. (2) Methods: The data from consecutive patients undergoing lead repositioning in two European referral centers were retrospectively analyzed. The odds ratio (OR) of CIED infection in the first year was compared among patients undergoing early (≤1 week) vs. delayed (>1 week to 1 year) reoperation. (3) Results: Out of 249 patients requiring CIED reintervention, 85 patients (34%) underwent an early (median 2 days) and 164 (66%) underwent a delayed lead revision (median 53 days). A total of nine (3.6%) wound/device infections were identified. The risk of infection was numerically lower in the early (1.2%) vs. delayed (4.9%) intervention group yielding no statistically significant difference, even after adjustment for typical risk factors for CIED infection (adjusted OR = 0.264, 95% CI 0.032-2.179, p = 0.216). System explantation/extraction was necessary in seven cases, all being revised in the delayed group. (4) Conclusions: In this bicentric, international study, delayed lead repositioning did not reduce the risk of CIED infection.

Phenogrouping and risk stratification of patients undergoing cardiac resynchronization therapy upgrade using topological data analysis.

Choosing the optimal device during cardiac resynchronization therapy (CRT) upgrade can be challenging. Therefore, we sought to provide a solution for identifying patients in whom upgrading to a CRT-defibrillator (CRT-D) is associated with better long-term survival than upgrading to a CRT-pacemaker (CRT-P). To this end, we first applied topological data analysis to create a patient similarity network using 16 clinical features of 326 patients without prior ventricular arrhythmias who underwent CRT upgrade. Then, in the generated circular network, we delineated three phenogroups exhibiting significant differences in clinical characteristics and risk of all-cause mortality. Importantly, only in the high-risk phenogroup was upgrading to a CRT-D associated with better survival than upgrading to a CRT-P (hazard ratio: 0.454 (0.228-0.907), p = 0.025). Finally, we assigned each patient to one of the three phenogroups based on their location in the network and used this labeled data to train multi-class classifiers to enable the risk stratification of new patients. During internal validation, an ensemble of 5 multi-layer perceptrons exhibited the best performance with a balanced accuracy of 0.898 (0.854-0.942) and a micro-averaged area under the receiver operating characteristic curve of 0.983 (0.980-0.986). To allow further validation, we made the proposed model publicly available ( https://github.com/tokmarton/crt-upgrade-risk-stratification ).

Ultrasound guidance for femoral venous access in patients undergoing pulmonary vein isolation: A quasi-randomized study.

INTRODUCTION: Routine ultrasound (US) guidance for femoral venous access to decrease vascular complications of atrial fibrillation (AF) ablation procedures has been advocated. However, the benefit has not been unequivocally demonstrated by randomized-trial data. METHODS: Consecutive patients undergoing pulmonary vein isolation (PVI) on uninterrupted anticoagulant treatment were included. A quasi-random allocation to either US-guided or conventional puncture group was based on which of the two procedure rooms the patient was scheduled in, with only one of the rooms equipped with a US machine including a vascular transducer. The same four novice operators in rotation, with no relevant previous experience in US-guided vascular access performed venous punctures in both rooms. Major and minor vascular complications and the rate of prolonged hospitalization were compared. Major vascular complication was defined as groin hematoma, arteriovenous fistula, or pseudoaneurysm. Hematoma was considered as a major vascular complication if it met type 2 or higher Bleeding Academic Research Consortium criteria (requiring nonsurgical, medical intervention by a health care professional; leading to hospitalization or increased level of care, or prompting evacuation). RESULTS: Of the 457 patients 199 were allocated to the US-guided puncture group, while the conventional, palpation-based approach was performed in 258 cases. Compared with the conventional technique, US guidance reduced the rate of any vascular complication (11.63% vs. 2.01%, p < .0001), including both major (4.26% vs. 1.01%, p = .038) and minor (7.36% vs. 1.01%, p = .001) vascular complications. In addition, the rate of prolonged hospitalization was lower in the US-guided puncture group (5.04% vs. 1.01%, p = .032). CONCLUSION: The use of US for femoral vein puncture in patients undergoing PVI decreased the rate of both major and minor vascular complications. This quasi-randomized comparison strongly supports adapting routine use of US for AF ablation procedures.

A head-to-head comparison of laser vs. powered mechanical sheaths as first choice and second line extraction tools.

AIMS: During transvenous lead extraction (TLE) longer dwelling time often requires the use of powered sheaths. This study aimed to compare outcomes with the laser and powered mechanical tools. METHODS AND RESULTS: Single-centre data from consecutive patients undergoing TLE between 2012 and 2021 were retrospectively analysed. Efficacy and safety of the primary extraction tool were compared. Procedures requiring crossover between powered sheaths were also analysed. Moreover, we examined the efficacy of each level of the stepwise approach. Out of 166 patients, 142 (age 65.4 ± 13.7 years) underwent TLE requiring advanced techniques with 245 leads (dwelling time 9.4 ± 6.3 years). Laser sheaths were used in 64.9%, powered mechanical sheaths in 35.1% of the procedures as primary extraction tools. Procedural success rate was 85.5% with laser and 82.5% with mechanical sheaths (P = 0.552). Minor and major complications were observed in similar rate. Procedural mortality occurred only in the laser group in the case of three patients. Crossover was needed in 19.5% after laser and in 12.8% after mechanical extractions (P = 0.187). Among crossover procedures, only clinical success favoured the secondary mechanical arm (87.1 vs. 54.5%, aOR: 0.09, 95% CI: 0.01-0.79, P = 0.030). After step-by-step efficacy analysis, procedural success was 64.9% with the first-line extraction tool, 75.1% after crossover, 84.5% with bailout femoral snare, and 91.8% by non-emergency surgery. CONCLUSION: The efficacy and safety of laser and mechanical sheaths were similar, however in the subgroup of crossover procedures mechanical tools had better performance regarding clinical success. Device diversity seems to help improving outcomes, especially in the most complicated cases.

Reimplantation and long-term mortality after transvenous lead extraction in a high-risk, single-center cohort.

PURPOSE: The use of cardiac implantable electronic devices (CIEDs) has increased significantly over the last decades. With the development of transvenous lead extraction (TLE), procedural success rates also improved; however, data regarding long-term outcomes are still limited. The aim of our study was to analyze the outcomes after TLE, including reimplantation data, all-cause and cause-specific mortality. METHODS: Data from consecutive patients undergoing TLE in our institution between 2012 and 2020 were retrospectively analyzed. Periprocedural, 30-day, long-term, and cause-specific mortalities were calculated. We examined the original and the revised CIED indications and survival rate of patients with or without reimplantation. RESULTS: A total of 150 patients (age 66 ± 14 years) with 308 leads (dwelling time 7.8 ± 6.3 years) underwent TLE due to pocket infection (n = 105, 70%), endocarditis (n = 35, 23%), or non-infectious indications (n = 10, 7%). All-cause mortality data were available for all patients, detailed reimplantation data in 98 cases. Procedural death rate was 2% (n = 3), 30-day mortality rate 2.6% (n = 4). During the 3.5 ± 2.4 years of follow-up, 44 patients died. Arrhythmia, as the direct cause of death, was absent. Cardiovascular cause was responsible for mortality in 25%. There was no significant survival difference between groups with or without reimplantation (p = 0.136). CONCLUSIONS: Despite the high number of pocket and systemic infection and long dwelling times in our cohort, the short- and long-term mortality after TLE proved to be favorable. Moreover, survival without a new device was not worse compared to patients who underwent a reimplantation procedure. Our study underlines the importance of individual reassessment of the original CIED indication, to avoid unnecessary reimplantation.

Inability to perform 'en bloc' pulmonary vein isolation requiring ablation of the intervenous carina increases recurrence of atrial fibrillation: A meta-analysis.

INTRODUCTION: Failure to isolate ipsilateral pulmonary veins (PV) "en bloc" by wide-area circumferential ablation (WACA) may necessitate ablation at the intervenous carina. It is unknown how this scenario impacts rates of atrial fibrillation (AF) recurrence. METHODS: A standard random-effect meta-analysis of randomized or observational studies were performed, where the outcome of first-time AF ablation was reported in patients with "en bloc" isolation of PVs by WACA as compared with those in whom ablation at the intervenous carina was needed after WACA to achieve complete isolation. RESULTS: A total of five single-center, observational studies (N = 1185) and one, multi-center randomized trial (N = 234) were enrolled. PV isolation could be achieved by WACA "en bloc" in 902/1419 (63.6%) cases. The rest required additional ablation at one or both of the left and right intervenous carinas to achieve isolation. The follow-up time after ablation ranged from 1 to 2 years in the included trials. The incidence of AF recurrence proved to be significantly lower in patients with successful "en bloc" isolation compared to those requiring carina ablation(s) to achieve complete bilateral PV isolation (MH-OR 1.89, 95% CI 1.42-2.53, p < .01) CONCLUSION: This present meta-analysis demonstrates a lower arrhythmia recurrence rate in patients with bilateral "en bloc" isolation, as compared to those who needed additional carina ablation for complete PVI. Therefore, it is imperative that every effort be made to isolate ipsilateral PVs "en bloc" during PVI.

Baseline clinical characteristics of heart failure patients with reduced ejection fraction enrolled in the BUDAPEST-CRT Upgrade trial.

AIMS: The BUDAPEST-CRT Upgrade study is the first prospective, randomized, multicentre clinical trial investigating the outcomes after cardiac resynchronization therapy (CRT) upgrade in heart failure (HF) patients with intermittent or permanent right ventricular (RV) pacing with wide paced QRS. This report describes the baseline clinical characteristics of the enrolled patients and compares them to cohorts from previous milestone CRT studies. METHODS AND RESULTS: This international multicentre randomized controlled trial investigates 360 patients having a pacemaker (PM) or implantable cardioverter defibrillator (ICD) device for at least 6 months prior to enrolment, reduced left ventricular ejection fraction (LVEF ≤35%), HF symptoms (New York Heart Association [NYHA] functional class II-IVa), wide paced QRS (>150 ms), and ≥20% of RV pacing burden without having a native left bundle branch block. At enrolment, the mean age of the patients was 73 ± 8 years; 89% were male, 97% were in NYHA class II/III functional class, and 56% had atrial fibrillation. Enrolled patients predominantly had conventional PM devices, with a mean RV pacing burden of 86%. Thus, this is a patient cohort with advanced HF, low baseline LVEF (25 ± 7%), high N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (2231 pg/ml [25th-75th percentile 1254-4309 pg/ml]), and frequent HF hospitalizations during the preceding 12 months (50%). CONCLUSION: When compared with prior CRT trial cohorts, the BUDAPEST-CRT Upgrade study includes older patients with a strong male predominance and a high burden of atrial fibrillation and other comorbidities. Moreover, this cohort represents an advanced HF population with low LVEF, high NT-proBNP, and frequent previous HF events. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02270840.

Is prophylactic ablation of the cavotricuspid and peri-incisional isthmus justified in patients with postoperative atrial flutter after right atriotomy?

BACKGROUND: The two most common postoperative atrial flutter (AFL) circuits after right atriotomy are the cavotricuspid isthmus (CTI) dependent and the lateral, peri-incisional. We investigated whether radiofrequency ablation (RFA) of both circuits results in more favorable long-term outcomes. METHODS: Single-center retrospective cohort study of consecutive patients who underwent RFA of AFL after open-heart surgery. The effect of surgery type and RFA strategy on AFL recurrence was evaluated. RESULTS: One hundred and forty-two patients (mean age 64.5 ± 12.7 years, 65.% male) were enrolled. Patients with right atrial (RA) flutter (n = 124) were divided into two groups based on the index RFA procedure: only one RA circuit was ablated (Group 1, n = 84, 67.7%) or both the CTI and the peri-incisional circuit ablated (Group 2, n = 40, 32.3%). The previous open-heart surgery was categorized based on the extension of the RA incision: limited (Type A) or extended (Type B) atriotomy. After a mean follow-up of 36 ± 28 months, flutter recurrence was not different among patients with limited RA atriotomy (25% vs. 22% in Groups 1A and 2A, respectively, p = 1.0). However, after type B surgery, ablation of both AFL circuits was associated with a reduced recurrence rate (63% vs. 26% in Groups 1B and 2B, respectively, p = .002). CONCLUSIONS: In patients with postoperative RA flutter after extended right atriotomy, ablation of both the CTI and the peri-incisional isthmus significantly reduces the AFL recurrence rate. Prophylactic ablation of both isthmi, even if not proven to support reentry, is reasonable in this population.

Implantation of a VDD implantable cardioverter-defibrillator lead via a persistent left superior vena cava.

A persistent left superior vena cava (LSVC) represents a challenging congenital abnormality for transvenous cardiac device implantation. In the current case a secondary prophylactic VDD implantable cardioverter-defibrillator (ICD) implantation was planned in a 75-year-old woman presenting with ischemic cardiomyopathy and elevated stroke risk. Since no venous communication to the right side was identified intraoperatively, the lead was placed via the persistent LSVC. The far-field signal on the floating atrial dipole could be successfully blanked out, and appropriate device function with high and stable atrial sensing was demonstrated at follow-up.

Randomized trial of intracardiac echocardiography-guided slow pathway ablation.

PURPOSE: Radiofrequency (RF) catheter ablation of the slow pathway (SP) in atrioventricular nodal reentry tachycardia (AVNRT) is highly effective; however, it may require prolonged fluoroscopy and RF time. We postulated that visualization of the SP region with intracardiac echocardiography (ICE) could decrease ablation time, minimize radiation exposure, and facilitate SP ablation compared to the standard, fluoroscopy-guided approach. METHODS: In our study, we randomized 91 patients undergoing electrophysiologic study and SP ablation for AVNRT into 2 groups: fluoroscopy-only (n = 48) or ICE-guided (n = 43) group. Crossover to ICE-guidance was allowed after 8 unsuccessful RF applications. RESULTS: Mapping plus ablation time (mean ± standard deviation: 18.8 ± 16.1 min vs 11.6 ± 15.0 min, p = 0.031), fluoroscopy time (median [interquartile range]: 4.9 [2.93-8.13] min vs. 1.8 [1.2-2.8] min, p < 0.001), and total ablation time (144 [104-196] s vs. 81 [60-159] s, p = 0.001) were significantly shorter in the ICE group. ICE-guidance was associated with reduced radiation exposure (13.2 [8.2-13.4] mGy vs. 3.7 [1.5-5.8] mGy, p < 0.001). The sum of delivered RF energy (3866 [2786-5656] Ws vs. 2283 [1694-4284] Ws, p = 0.002) and number of RF applications (8 [4.25-12.75] vs. 4 [2-7], p = 0.001) were also lower with ICE-guidance. Twelve (25%) patients crossed over to the ICE-guided group. All were treated successfully thereafter with similar number, time, and cumulative energy of RF applications compared to the ICE group. No recurrence occurred during the follow-up. CONCLUSIONS: ICE-guidance during SP ablation significantly reduces mapping and ablation time, radiation exposure, and RF delivery in comparison to fluoroscopy-only procedures. Moreover, early switching to ICE-guided ablation seems to be an optimal choice in challenging cases.

Limitations of ventricular pacing maneuvers to differentiate orthodromic reciprocating tachycardia from atrioventricular nodal reentry tachycardia.

PURPOSE: Various ventricular pacing maneuvers have been developed to differentiate orthodromic reciprocating tachycardia (ORT) from atrioventricular nodal reentry tachycardia (AVNRT). We aimed to evaluate the diagnostic value of ventricular pacing maneuvers in patients undergoing catheter ablation for AVNRT/ORT. METHODS: Sixty patients with supraventricular tachycardia (SVT) undergoing invasive EP study were included (ORT: 31, typical AVNRT: 18, atypical AVNRT: 11). Ventricular overdrive pacing (VOP) and resetting by premature ventricular stimulation (PVS) during SVT were analyzed by 3 independent observers blinded to the ultimate diagnosis. We determined intraclass correlation coefficient (ICC) for interobserver agreement and the diagnostic accuracy of consensual results. RESULTS: Although specificity of all parameters was high (96-100%) for ORT, semi-quantitative parameters of VOP (requiring the recognition of specific ECG patterns) had lower interobserver reliability (ICC: 0.32-0.66) and sensitivity (16.1-77.4%). In contrast, most quantitative measurements of VOP and PVS showed good reproducibility (ICC: 0.93-0.95) and sensitivity (74.2-89.3%), but post-pacing interval after VOP needed correction with AV nodal conduction slowing. False negative results for diagnosing ORT were more common with left free wall vs. right free wall or septal, and slowly vs. fast-conducting septal APs. False positivity was only seen with a bystander, concealed nodo-fascicular/nodo-ventricular (NF/NV) AP in a case of AVNRT. CONCLUSIONS: No single maneuver is 100% sensitive for ORT. Semi-quantitative features have limited reproducibility and all parameters can be misleading in the case of rate-dependent delay during VOP/PVS, ORT circuits remote from the pacing site, or a bystander, concealed NF/NV AP.

Management of cardiac implantable electronic device infection using a complete interdisciplinary approach.

Technological advances and increasing operator experience have improved the success rate of transvenous lead extraction (TLE). However, in some cases-especially with longer lead dwelling time-TLE can be highly complicated. In this case report, the authors present an unusual case of implantable cardioverter defibrillator (ICD) pocket infection diagnosed by 18F­fluorodeoxyglucose positron emission tomography/computed tomography (18F­FDG-PET/CT). Complete lead extraction required a combined transvenous and surgical approach. Contralateral reimplantation failed due to occlusion of the right brachiocephalic vein. Therefore, a subcutaneous ICD was implanted. This case highlights the importance of an interdisciplinary approach to the treatment of cardiac implantable electronic device infection.

Atrial Remodeling in Atrial Fibrillation. Comorbidities and Markers of Disease Progression Predict Catheter Ablation Outcome.

Atrial fibrillation is the most common supraventricular arrhythmia affecting an increasing proportion of the population in which mainstream therapy, i.e. catheter ablation, provides freedom from arrhythmia in only a limited number of patients. Understanding the mechanism is key in order to find more effective therapies and to improve patient selection. In this review, the structural and electrophysiological changes of the atrial musculature that constitute atrial remodeling in atrial fibrillaton and how risk factors and markers of disease progression can predict catheter ablation outcome will be discussed in detail.

European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections-endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID), and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).

Pacemakers, implantable cardiac defibrillators, and cardiac resynchronization therapy devices are potentially lifesaving treatments for a number of cardiac conditions but are not without risk. Most concerning is the risk of a cardiac implantable electronic device (CIED) infection, which is associated with significant morbidity, increased hospitalizations, reduced survival, and increased health care costs. Recommended preventive strategies such as administration of intravenous antibiotics before implantation are well-recognized. Uncertainties have remained about the role of various preventive, diagnostic, and treatment measures such as skin antiseptics, pocket antibiotic solutions, antibacterial envelopes, prolonged antibiotics post-implantation, and others. When compared with previous guidelines or consensus statements, the present consensus document gives guidance on the use of novel device alternatives, novel oral anticoagulants, antibacterial envelopes, prolonged antibiotics post-implantation, as well as definitions on minimum quality requirements for centres and operators and volumes. The recognition that an international consensus document focused on management of CIED infections is lacking, the dissemination of results from new important randomized trials focusing on prevention of CIED infections, and observed divergences in managing device-related infections as found in an European Heart Rhythm Association worldwide survey, provided a strong incentive for a Novel 2019 International State-of-the-art Consensus document on risk assessment, prevention, diagnosis, and treatment of CIED infections.

European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections-endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).

Pacemakers, implantable cardiac defibrillators, and cardiac resynchronization therapy devices are potentially life-saving treatments for a number of cardiac conditions, but are not without risk. Most concerning is the risk of a cardiac implantable electronic device (CIED) infection, which is associated with significant morbidity, increased hospitalizations, reduced survival, and increased healthcare costs. Recommended preventive strategies such as administration of intravenous antibiotics before implantation are well recognized. Uncertainties have remained about the role of various preventive, diagnostic, and treatment measures such as skin antiseptics, pocket antibiotic solutions, anti-bacterial envelopes, prolonged antibiotics post-implantation, and others. Guidance on whether to use novel device alternatives expected to be less prone to infections and novel oral anticoagulants is also limited, as are definitions on minimum quality requirements for centres and operators and volumes. Moreover, an international consensus document on management of CIED infections is lacking. The recognition of these issues, the dissemination of results from important randomized trials focusing on prevention of CIED infections, and observed divergences in managing device-related infections as found in an European Heart Rhythm Association worldwide survey, provided a strong incentive for a 2019 International State-of-the-art Consensus document on risk assessment, prevention, diagnosis, and treatment of CIED infections.

European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections-endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).

Pacemakers, implantable cardiac defibrillators, and cardiac resynchronization therapy devices are potentially life-saving treatments for a number of cardiac conditions, but are not without risk. Most concerning is the risk of a cardiac implantable electronic device (CIED) infection, which is associated with significant morbidity, increased hospitalizations, reduced survival, and increased healthcare costs. Recommended preventive strategies such as administration of intravenous antibiotics before implantation are well recognized. Uncertainties have remained about the role of various preventive, diagnostic, and treatment measures such as skin antiseptics, pocket antibiotic solutions, anti-bacterial envelopes, prolonged antibiotics post-implantation, and others. Guidance on whether to use novel device alternatives expected to be less prone to infections and novel oral anticoagulants is also limited, as are definitions on minimum quality requirements for centres and operators and volumes. Moreover, an international consensus document on management of CIED infections is lacking. The recognition of these issues, the dissemination of results from important randomized trials focusing on prevention of CIED infections, and observed divergences in managing device-related infections as found in an European Heart Rhythm Association worldwide survey, provided a strong incentive for a 2019 International State-of-the-art Consensus document on risk assessment, prevention, diagnosis, and treatment of CIED infections.