The potential of artificial intelligence to revolutionize health care delivery, research, and education in cardiac electrophysiology.

The field of electrophysiology (EP) has benefited from numerous seminal innovations and discoveries that have enabled clinicians to deliver therapies and interventions that save lives and promote quality of life. The rapid pace of innovation in EP may be hindered by several challenges including the aging population with increasing morbidity, the availability of multiple costly therapies that, in many instances, confer minor incremental benefit, the limitations of healthcare reimbursement, the lack of response to therapies by some patients, and the complications of the invasive procedures performed. To overcome these challenges and continue on a steadfast path of transformative innovation, the EP community must comprehensively explore how artificial intelligence (AI) can be applied to healthcare delivery, research, and education and consider all opportunities in which AI can catalyze innovation; create workflow, research, and education efficiencies; and improve patient outcomes at a lower cost. In this white paper, we define AI and discuss the potential of AI to revolutionize the EP field. We also address the requirements for implementing, maintaining, and enhancing quality when using AI and consider ethical, operational, and regulatory aspects of AI implementation. This manuscript will be followed by several perspective papers that will expand on some of these topics.

ForCEPSS-A framework for cardiac electrophysiology simulations standardization.

BACKGROUND AND OBJECTIVE: Simulation of cardiac electrophysiology (CEP) is an important research tool that is increasingly being adopted in industrial and clinical applications. Typical workflows for CEP simulation consist of a sequence of processing stages starting with building an anatomical model and then calibrating its electrophysiological properties to match observable data. While the calibration stages are common and generalizable, most CEP studies re-implement these steps in complex and highly variable workflows. This lack of standardization renders the execution of computational CEP studies in an efficient, robust, and reproducible manner a significant challenge. Here, we propose ForCEPSS as an efficient and robust, yet flexible, software framework for standardizing CEP simulation studies. METHODS AND RESULTS: Key processing stages of CEP simulation studies are identified and implemented in a standardized workflow that builds on openCARP1 Plank et al. (2021) and the Python-based carputils2 framework. Stages include (i) the definition and initialization of action potential phenotypes, (ii) the tissue scale calibration of conduction properties, (iii) the functional initialization to approximate a limit cycle corresponding to the dynamic reference state according to an experimental protocol, and, (iv) the execution of the CEP study where the electrophysiological response to a perturbation of the limit cycle is probed. As an exemplar application, we employ ForCEPSS to prepare a CEP study according to the Virtual Arrhythmia Risk Prediction protocol used for investigating the arrhythmogenic risk of developing infarct-related ventricular tachycardia (VT) in ischemic cardiomyopathy patients. We demonstrate that ForCEPSS enables a fully automated execution of all stages of this complex protocol. CONCLUSION: ForCEPSS offers a novel comprehensive, standardized, and automated CEP simulation workflow. The high degree of automation accelerates the execution of CEP simulation studies, reduces errors, improves robustness, and makes CEP studies reproducible. Verification of simulation studies within the CEP modeling community is thus possible. As such, ForCEPSS makes an important contribution towards increasing transparency, standardization, and reproducibility of in silico CEP experiments.

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.

Stereotactic arrhythmia radioablation and its implications for modern cardiac electrophysiology: results of an EHRA survey.

Stereotactic arrhythmia radioablation (STAR) is a treatment option for recurrent ventricular tachycardia/fibrillation (VT/VF) in patients with structural heart disease (SHD). The current and future role of STAR as viewed by cardiologists is unknown. The study aimed to assess the current role, barriers to application, and expected future role of STAR. An online survey consisting of 20 questions on baseline demographics, awareness/access, current use, and the future role of STAR was conducted. A total of 129 international participants completed the survey [mean age 43 ± 11 years, 25 (16.4%) female]. Ninety-one (59.9%) participants were electrophysiologists. Nine participants (7%) were unaware of STAR as a therapeutic option. Sixty-four (49.6%) had access to STAR, while 62 (48.1%) had treated/referred a patient for treatment. Common primary indications for STAR were recurrent VT/VF in SHD (45%), recurrent VT/VF without SHD (7.8%), or premature ventricular contraction (3.9%). Reported main advantages of STAR were efficacy in the treatment of arrhythmias not amenable to conventional treatment (49%) and non-invasive treatment approach with overall low expected acute and short-term procedural risk (23%). Most respondents have foreseen a future clinical role of STAR in the treatment of VT/VF with or without underlying SHD (72% and 75%, respectively), although only a minority expected a first-line indication for it (7% and 5%, respectively). Stereotactic arrhythmia radioablation as a novel treatment option of recurrent VT appears to gain acceptance within the cardiology community. Further trials are critical to further define efficacy, patient populations, as well as the appropriate clinical use for the treatment of VT.

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.

[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)

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)