Conduction system pacing versus biventricular pacing in heart failure with reduced ejection fraction: a systematic review and meta-analysis of randomized clinical trials I

BACKGROUND: Biventricular pacing (BVP) has proven efficacy in treating heart failure with reduced ejection fraction (HFrEF) and ventricular dyssynchrony. Conduction system pacing (CSP), encompassing His bundle pacing (HBP) and left bundle area pacing (LBAP), has emerged as a promising alternative, but its benefits are still uncertain. METHODS: PubMed, Scopus and Cochrane databases were searched for randomized controlled trials (RCTs) that compared CSP to BVP for resynchronization therapy in patients with HFrEF and reported the outcomes of (1) paced QRS interval duration; (2) left ventricular ejection fraction (LVEF); and (3) New York Heart Association functional class (NYHA). Heterogeneity was examined with I² statistics. A random-effects model was used for all outcomes. RESULTS: We included 7 RCTs with 408 patients, of whom 200 (49%) underwent CSP. In patients undergoing CSP, there was significantly lower paced QRS duration (MD -13.34; 95% CI -24.32 to -2.36; p=0.02; Figure 1) and NYHA functional class (SMD -0.37; 95% CI -0.69 to -0.05; p=0.02; Figure 2). There was also a significant increase in LVEF in the CSP group (MD 2.06; 95% CI 0.16 to 3.97; p=0.03; Figure 3). No statistical difference was noted for LVESV (SMD -0.51; 95% CI -1.26 to 0.24; p=0.18; I²=83%), threshold for lead capture (MD -0.08; 95% CI -0.42 to 0.27; p=0.66; I²=66%), and procedure time (MD 5.99; 95% CI -15.91 to 27.89; p=0.59; I²=79%). Hospitalizations for HF were only noted in three studies, and no difference was observed between groups (9 vs 7; RR 1.02; 95% CI 0.21 to 4.90; p=0.98; I²=46%). Differences in mortality did not reach statistical significance (3 vs 8; RR 0.45; 95% CI 0.12 to 1.62; p=0.219; I²=0%). In subgroup analysis per CSP technique, there were no significant differences between groups for QRS duration and LVEF. LBAP was the main contributor for the significant difference observed in the NYHA functional class with a trend towards subgroup difference (p interaction=0.06). Although no significant difference was noted for the overall lead threshold, the LBAP subgroup had significantly lower values compared to HBP (p interaction=0.03). CONCLUSION: These findings suggest that CSP may have symptomatic, echocardiographic and electrophysiologic benefits for HFrEF patients requiring resynchronization.

Circadian Regulation of Cardiac Arrhythmias and Electrophysiology.

Circadian rhythms in physiology and behavior are ≈24-hour biological cycles regulated by internal biological clocks (ie, circadian clocks) that optimize organismal homeostasis in response to predictable environmental changes. These clocks are present in virtually all cells in the body, including cardiomyocytes. Many decades ago, clinicians and researchers became interested in studying daily patterns of triggers for sudden cardiac death, the incidence of sudden cardiac death, and cardiac arrhythmias. This review highlights historical and contemporary studies examining the role of day/night rhythms in the timing of cardiovascular events, delves into changes in the timing of these events over the last few decades, and discusses cardiovascular disease-specific differences in the timing of cardiovascular events. The current understanding of the environmental, behavioral, and circadian mechanisms that regulate cardiac electrophysiology is examined with a focus on the circadian regulation of cardiac ion channels and ion channel regulatory genes. Understanding the contribution of environmental, behavioral, and circadian rhythms on arrhythmia susceptibility and the incidence of sudden cardiac death will be essential in developing future chronotherapies.

Role of Computed Tomography in Cardiac Electrophysiology.

With the increasing prevalence of arrhythmias, the use of electrophysiology (EP) procedures has increased. Recent advancements in computed tomography (CT) technology have expanded its use in pre-assessments and post-assessments of EP procedures. CT provides high-resolution images, is noninvasive, and is widely available. This article highlights the strengths and weaknesses of cardiac CT in EP.

Participation in Competitive Sports by Patients With Congenital Heart Disease: AHA/ACC and EAPC/ESC/AEPC Guidelines Comparison.

Sports participation in patients with congenital heart disease is an evolving subject. The American Heart Association/American College of Cardiology released a set of guidelines that advise the type and level of sports participation based primarily on anatomical defects with secondary consideration given to hemodynamic effects. Recently, the European Association of Preventive Cardiology/European Society of Cardiology/Association for European Paediatric and Congenital Cardiology offered a contrasting approach to sports participation that is based on hemodynamic and electrophysiological profiles of each patient, regardless of anatomical consideration. These guidelines are drastically different in their approaches but do have some similarities. In this review, we compare both documents, focusing on the aim, population, classification of sports, and the methodology of making recommendations. This review aims to assist practicing cardiologists in integrating the available published data and recommendations when counseling patients for sports participation.

Deciphering the roles of triiodothyronine (T3) and thyroid-stimulating hormone (TSH) on cardiac electrical remodeling in clinical and experimental hypothyroidism

Hypothyroidism is the most frequent endocrine pathology. Although clinical or overt hypothyroidism has been traditionally associated to low T3 / T4 and high thyrotropin (TSH) circulating levels, other forms exist such as subclinical hypothyroidism, characterized by normal blood T3 / T4 and high TSH. In its different forms is estimated to affect approximately 10% of the population, especially women, in a 5:1 ratio with respect to men. Among its consequences are alterations in cardiac electrical activity, especially in the repolarization phase, which is accompanied by an increased susceptibility to cardiac arrhythmias. Although these alterations have traditionally been attributed to thyroid hormone deficiency, recent studies, both clinical trials and experimental models, demonstrate a fundamental role of TSH in cardiac electrical remodeling. Thus, both metabolic thyroid hormones and TSH regulate cardiac ion channel expression in many and varied ways. This means that the different combinations of hormones that predominate in different types of hypothyroidism (overt, subclinic, primary, central) can generate different forms of cardiac electrical remodeling. These new findings are raising the relevant question of whether serum TSH reference ranges should be redefined. (AU)

[Historical development of diagnosis of bradyarrhythmias : The early years of clinical electrophysiology in Germany]. / Historische Entwicklung der Diagnostik der bradykarden Rhythmusstörungen : Die frühen Jahre der Klinischen Elektrophysiologie in Deutschland.

The introduction of His bundle electrography by Benjamin Scherlag (New York) in 1969, together with programmed stimulation of the heart by Philip Coumel (Paris) in 1967, and Hein Wellens (Amsterdam) in 1972, were decisive turning points on the way to invasive electrophysiology and the development of an independent, now distinctly interventional subspecialty of cardiology. The main topic of the 1970s was bradycardic arrhythmias, promoted by pacemaker therapy, which had been introduced just over 10 years earlier. The recording of the potentials of the bundle of His and other recording locations in the atria and ventricles allowed a differentiated assessment of the excitation process and the refractory periods. High-rate atrial stimulation to determine sinus node recovery time and premature stimulation to determine sinoatrial conduction time were developed to analyze sinoatrial node function. This article describes the introduction of His bundle electrography in a gradually increasing number of centers in Germany and their scientific contribution.

[Development of catheter ablation of supraventricular tachycardias with special consideration of contributions from German engineers and electrophysiologists]. / Entwicklung der Katheterablation supraventrikulärer Tachykardien unter besonderer Berücksichtigung der Beiträge deutscher Ingenieure und Elektrophysiologen.

The development and clinical implementation of catheter ablation of supraventricular tachycardia is one of the outstanding achievements of modern cardiovascular treatment. Over a period of less than 40 years, a curative and safe treatment strategy for almost all forms of atrial arrhythmias has been developed and implemented. German electrophysiologists and engineers have made a significant contribution to this truly outstanding success story in modern medicine. Their contributions should be appropriately acknowledged because without them, the development of ablation technology and its worldwide dissemination would not have been possible. Both the technological contributions and the medical-electrophysiological contributions were at the absolute forefront of worldwide developments and have made a significant contribution to the fact that today more than 500,000 patients with symptomatic and/or threatening cardiac arrhythmias can be successfully treated every year by use of catheter ablation. We would like to thank them all for their achievements.

Deciphering the roles of triiodothyronine (T3) and thyroid-stimulating hormone (TSH) on cardiac electrical remodeling in clinical and experimental hypothyroidism

Hypothyroidism is the most frequent endocrine pathology. Although clinical or overt hypothyroidism has been traditionally associated to low T3 / T4 and high thyrotropin (TSH) circulating levels, other forms exist such as subclinical hypothyroidism, characterized by normal blood T3 / T4 and high TSH. In its different forms is estimated to affect approximately 10% of the population, especially women, in a 5:1 ratio with respect to men. Among its consequences are alterations in cardiac electrical activity, especially in the repolarization phase, which is accompanied by an increased susceptibility to cardiac arrhythmias. Although these alterations have traditionally been attributed to thyroid hormone deficiency, recent studies, both clinical trials and experimental models, demonstrate a fundamental role of TSH in cardiac electrical remodeling. Thus, both metabolic thyroid hormones and TSH regulate cardiac ion channel expression in many and varied ways. This means that the different combinations of hormones that predominate in different types of hypothyroidism (overt, subclinic, primary, central) can generate different forms of cardiac electrical remodeling. These new findings are raising the relevant question of whether serum TSH reference ranges should be redefined. (AU)

Utilization of and perceived need for simulators in clinical electrophysiology: results from an EHRA physician survey.

AIMS: Simulator training has been recently introduced in electrophysiology (EP) programmes in order to improve catheter manipulation skills without complication risks. The aim of this study is to survey the current use of EP simulators and the perceived need for these tools in clinical training and practice. METHODS AND RESULTS: A 20-item online questionnaire developed by the Scientific Initiatives Committee of the European Heart Rhythm Association (EHRA) in collaboration with EHRA Digital Committee was disseminated through the EHRA Scientific Research Network members, national EP groups, and social media platforms. Seventy-four respondents from 22 countries (73% males; 50% under 40 years old) completed the survey. Despite being perceived as useful among EP professionals (81%), EP simulators are rarely a part of the institutional cardiology training programme (20%) and only 18% of the respondents have an EP simulator at their institution. When available, simulators are mainly used in EP to train transseptal puncture, ablation, and mapping, followed by device implantation (cardiac resynchronization therapy [CRT], leadless, and conduction system pacing [CSP]). Almost all respondents (96%) believe that simulator programmes should be a part of the routine institutional EP training, hopefully developed by EHRA, in order to improve the efficacy and safety of EP procedures and in particular CSP 58%, CRT 42%, leadless pacing 38%, or complex arrhythmia ablations (VT 58%, PVI 45%, and PVC 42%). CONCLUSION: This current EHRA survey identified a perceived need but a lack of institutional simulator programme access for electrophysiologists who could benefit from it in order to speed up the learning curve process and reduce complications of complex EP procedures.

Thromboembolism prophylaxis practices of pediatric and congenital electrophysiologists during invasive electrophysiology studies: A PACES survey.

BACKGROUND: Thromboembolic events related to invasive electrophysiology studies, while rare, can have devastating consequences. Use of systemic anticoagulation for a pediatric or adult-congenital invasive electrophysiology study is recommended, however there is no established standard of practice in this population. OBJECTIVE: To report on procedural practices for thromboembolism prophylaxis during invasive electrophysiology studies for pediatric patients and adults with congenital heart disease. METHODS: An anonymous web-based survey was sent to the members of the Pediatric and Congenital Electrophysiology Society. The survey focused on pre-procedural, intra-procedural, and post-procedural thromboembolism prophylaxis practices during invasive electrophysiology studies. Significant practice variation was defined as <90% concordance among respondents. RESULTS: Survey was completed by 73 members; 52 (71%) practicing in the United States, 65 (89%) practicing in an academic institution, and 14 (19%) in an institution that performs more than 200 invasive electrophysiology procedures annually. Responses showed significant variation in practice. Prior to an invasive electrophysiology procedure, 25% discontinue aspirin while 47% discontinue anticoagulants. Heparin is given for all procedures by 32%. When heparin is administered, the first dose is given by 32% after sheaths are placed, 42% after crossing into the systemic atrium, and 26% just prior to systemic-side ablation. Most target an activated clotting time between 200-300 seconds. Post systemic-side ablation, 58% do not initiate a heparin infusion. Post-procedural oral agents were initiated on day of procedure by 34% of respondents and on post-procedure day 1 by 53%. If treating with aspirin, 74% use low-dose (3-5 mg/kg or 81 mg daily), and 68% treat for 4-6 weeks. CONCLUSION: There is significant variation in thromboembolism prophylaxis for invasive EP studies among pediatric and congenital electrophysiologists. Further studies are needed to optimize the management of thromboembolism prophylaxis in this population.

Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review.

State-of-the-art innovations in optical cardiac electrophysiology are significantly enhancing cardiac research. A potential leap into patient care is now on the horizon. Optical mapping, using fluorescent probes and high-speed cameras, offers detailed insights into cardiac activity and arrhythmias by analysing electrical signals, calcium dynamics, and metabolism. Optogenetics utilizes light-sensitive ion channels and pumps to realize contactless, cell-selective cardiac actuation for modelling arrhythmia, restoring sinus rhythm, and probing complex cell-cell interactions. The merging of optogenetics and optical mapping techniques for 'all-optical' electrophysiology marks a significant step forward. This combination allows for the contactless actuation and sensing of cardiac electrophysiology, offering unprecedented spatial-temporal resolution and control. Recent studies have performed all-optical imaging ex vivo and achieved reliable optogenetic pacing in vivo, narrowing the gap for clinical use. Progress in optical electrophysiology continues at pace. Advances in motion tracking methods are removing the necessity of motion uncoupling, a key limitation of optical mapping. Innovations in optoelectronics, including miniaturized, biocompatible illumination and circuitry, are enabling the creation of implantable cardiac pacemakers and defibrillators with optoelectrical closed-loop systems. Computational modelling and machine learning are emerging as pivotal tools in enhancing optical techniques, offering new avenues for analysing complex data and optimizing therapeutic strategies. However, key challenges remain including opsin delivery, real-time data processing, longevity, and chronic effects of optoelectronic devices. This review provides a comprehensive overview of recent advances in optical mapping and optogenetics and outlines the promising future of optics in reshaping cardiac electrophysiology and therapeutic strategies.

Overcoming Uncertainties in Electrogram-Based Atrial Fibrillation Mapping: A Review.

In clinical rhythmology, intracardiac bipolar electrograms (EGMs) play a critical role in investigating the triggers and substrates inducing and perpetuating atrial fibrillation (AF). However, the interpretation of bipolar EGMs is ambiguous due to several aspects of electrodes, mapping algorithms and wave propagation dynamics, so it requires several variables to describe the effects of these uncertainties on EGM analysis. In this narrative review, we critically evaluate the potential impact of such uncertainties on the design of cardiac mapping tools on AF-related substrate characterization. Literature suggest uncertainties are due to several variables, including the wave propagation vector, the wave's incidence angle, inter-electrode spacing, electrode size and shape, and tissue contact. The preprocessing of the EGM signals and mapping density will impact the electro-anatomical representation and the features extracted from the local electrical activities. The superposition of multiple waves further complicates EGM interpretation. The inclusion of these uncertainties is a nontrivial problem but their consideration will yield a better interpretation of the intra-atrial dynamics in local activation patterns. From a translational perspective, this review provides a concise but complete overview of the critical variables for developing more precise cardiac mapping tools.

Assessment of Risk for Ventricular Tachycardia based on Extensive Electrophysiology Simulations.

Patients that have suffered a myocardial infarction are at high risk of developing ventricular tachycardia. Patient stratification is often determined by characterization of the underlying myocardial substrate by cardiac imaging methods. In this study, we show that computer modeling of cardiac electrophysiology based on personalized fast 3D simulations can help to assess patient risk to arrhythmia. We perform a large simulation study on 21 patient digital twins and reproduce successfully the clinical outcomes. In addition, we provide the sites which are prone to sustain ventricular tachycardias, i.e, onset sites around the scar region, and validate if they colocalize with exit sites from slow conduction channels.Clinical relevance- Fast electrophysiological simulations can provide advanced patient stratification indices and predict arrhythmic susceptibility to suffer from ventricular tachycardia in patients that have suffered a myocardial infarction.

Assessment of the Interelectrode Distance Effect over the Omnipole with High Multielectrode Arrays.

The development of high-density multielectrode catheters has significantly advanced cardiac electrophysiology mapping. High-density grid catheters have enabled the creation of a novel technique for reconstructing electrogram (EGM) signals known as "omnipole," which is believed to be more reliable than other methods, especially in terms of orientation independence. This study aims to evaluate how distance affects the omnipolar reconstruction of EGMs by comparing different configurations. Using an animal set up of perfused isolated rabbit hearts, recordings were taken using an ad hoc high-density epicardial multielectrode catheter. Inter-electrode distances ranging from 1 to 4 mm were analysed for their effect on the quality of resulting EGMs. Two biomarkers were computed to evaluate the robustness of the reconstructions: the areas contained within the bipolar loops and the amplitudes of the omnipoles. We hypothesised that both bipolar and omnipolar electrograms would be more robust at shorter inter-electrode distances. The results showed that an increase in distance triggers an increase in loop areas and amplitudes, which supports the hypothesis. This finding provides a more reliable estimate of wavefront propagation for the cross-omnipolar reconstruction method. These results emphasise the importance of distance in cardiac electrophysiology mapping and provide valuable insights into the use of high-density multielectrode catheters for EGM reconstruction.Clinical Relevance- The results of this study have direct clinical relevance in the application of the described techniques to recording systems in the cardiac electrophysiology laboratory, enabling clinicians to obtain more precise characterisation of signals in the myocardium.