Phenotypic spectrum of the first Belgian MYBPC3 founder: a large multi-exon deletion with a varying phenotype.

Background: Variants in the MYBPC3 gene are a frequent cause of hypertrophic cardiomyopathy (HCM) but display a large phenotypic heterogeneity. Founder mutations are often believed to be more benign as they prevailed despite potential negative selection pressure. We detected a pathogenic variant in MYBPC3 (del exon 23-26) in several probands. We aimed to assess the presence of a common haplotype and to describe the cardiac characteristics, disease severity and long-term outcome of mutation carriers. Methods: Probands with HCM caused by a pathogenic deletion of exon 23-26 of MYBPC3 were identified through genetic screening using a gene panel encompassing 59 genes associated with cardiomyopathies in a single genetic center in Belgium. Cascade screening of first-degree relatives was performed, and genotype positive relatives were further phenotyped. Clinical characteristics were collected from probands and relatives. Cardiac outcomes included death, heart transplantation, life-threatening arrhythmia, heart failure hospitalization or septal reduction therapy. Haplotype analysis, using microsatellite markers surrounding MYBPC3, was performed in all index patients to identify a common haplotype. The age of the founder variant was estimated based on the size of the shared haplotype using a linkage-disequilibrium based approach. Results: We identified 24 probands with HCM harbouring the MYBPC3 exon 23-26 deletion. Probands were on average 51 ± 16 years old at time of clinical HCM diagnosis and 62 ± 10 years old at time of genetic diagnosis. A common haplotype of 1.19 Mb was identified in all 24 probands, with 19 of the probands sharing a 13.8 Mb haplotype. The founder event was estimated to have happened five generations, or 175-200 years ago, around the year 1830 in central Flanders. Through cascade screening, 59 first-degree relatives were genetically tested, of whom 37 (62.7%) were genotype positive (G+) and 22 (37.3%) genotype negative (G-). They were on average 38 ± 19 years old at time of genetic testing. Subsequent clinical assessment revealed a HCM phenotype in 19 (51.4%) G+ relatives. Probands were older (63 ± 10 vs. 42 ± 21 years; p < 0.001) and had more severe phenotypes than G+ family members, presenting with more symptoms (50% vs. 13.5%; p = 0.002), arrhythmia (41.7% vs. 12.9%, p = 0.014), more overt hypertrophy and left ventricular outflow tract obstruction (43.5% vs. 3.0%; p < 0.001). Male G+ relatives more often had a HCM phenotype (78.6% vs. 34.8%; p = 0.010) and were more severely affected than females. At the age of 50, a penetrance of 78.6% was observed, defined as the presence of HCM in 11 of 14 G+ relatives with age ≥50 years. Overall, 20.3% of all variant carriers developed one of the predefined cardiac outcomes after a median follow-up of 5.5 years with an average age of 50 (±21) years. Conclusion: A Belgian founder variant, an exon 23-26 deletion in MYBPC3, was identified in 24 probands and 37 family members. The variant is characterized by a high penetrance of 78.6% at the age of 50 years but has variable phenotypic expression. Adverse outcomes were observed in 20.3% of patients during follow-up.

Occupational radiation exposure of electrophysiology staff with reproductive potential and during pregnancy: an EHRA survey.

AIMS: Electrophysiology (EP) is a growing field in cardiology, with an increasing involvement of young people. Nevertheless, concerns about radiation exposure and its impact on reproduction and pregnancy may discourage the choice of an EP career. The study is aimed at investigating the level of awareness and main sources of concern about the effects of radiation on reproductive potential and pregnancy, exploring the safety measures adopted in different EP labs, and verifying the adherence to the current guidelines. METHODS AND RESULTS: An online survey was conducted using the European Heart Rhythm Association (EHRA) infrastructure from April to June 2022. A total of 252 EP personnel (42% women) participated, from 50 countries and different professional roles. Most participants expressed concerns regarding the effects of radiation on reproductive capacity (67.1%) and offspring diseases (68.2%). Only 37.9% of participants were aware of the EHRA 2017 consensus document about occupational radiation exposure. Most participants (80.9%) considered that occupational radiation during pregnancy is not safe. EP female staff were not allowed to work in the EP lab during pregnancy in 48.1% of cases. Zero-fluoroscopy was the preferred choice to continue working in the EP lab during pregnancy. CONCLUSION: EP staff, including both men and women, have concerns about the effects of radiation on reproductive capacity. Despite the recommendations issued by international bodies, implementation of the policies regarding pregnancy and occupational radiation exposure is heterogeneous. Zero-fluoroscopy is the preferred approach to ensure safety during pregnancy in the EP lab.

Worldwide sedation strategies for atrial fibrillation ablation: current status and evolution over the last decade.

Catheter ablation for atrial fibrillation (AF) has become one of the most common procedures in the electrophysiology lab with rapidly increasing volumes. Peri-procedural anaesthesia for AF ablation varies between centres, from general anaesthesia to deep or conscious sedation. The aim of this survey was to assess current sedation practices for AF ablation worldwide and its evolution over the last decade. Centres regularly performing AF ablation responded to an online survey. A total of 297 centres participated in the survey. Overall, the median (interquartile range) number of AF ablation procedures increased from 91 (43-200) to 200 (74-350) per year (P < 0.001) between 2010 and 2019. The proportion of cryoablation also increased from 17.0% to 33.2% (P < 0.001). In 2019, the most used sedation technique was general anaesthesia (40.5%), followed by conscious sedation (32.0%) and deep sedation (27.5%). Between 2010 and 2019, the proportion of procedures performed under general anaesthesia (+4.4%; P = 0.02) and deep sedation (+4.8%; P < 0.01) increased, whereas the use of conscious sedation decreased (-9.2%; P < 0.001). The most commonly used hypnotic drugs were propofol and midazolam, whereas the most commonly used opioid drugs were remifentanyl and fentanyl. This worldwide survey shows that the number of AF ablation procedures has more than doubled over the last decade and general anaesthesia remains most commonly used. Studies comparing outcomes between different sedation strategies are needed to guide optimal decision-making.

Current perspectives on wearable rhythm recordings for clinical decision-making: the wEHRAbles 2 survey.

Novel wearable devices for heart rhythm analysis using either photoplethysmography (PPG) or electrocardiogram (ECG) are in daily clinical practice. This survey aimed to assess impact of these technologies on physicians' clinical decision-making and to define, how data from these devices should be presented and integrated into clinical practice. The online survey included 22 questions, focusing on the diagnosis of atrial fibrillation (AF) based on wearable rhythm device recordings, suitable indications for wearable rhythm devices, data presentation and processing, reimbursement, and future perspectives. A total of 539 respondents {median age 38 [interquartile range (IQR) 34-46] years, 29% female} from 51 countries world-wide completed the survey. Whilst most respondents would diagnose AF (83%), fewer would initiate oral anticoagulation therapy based on a single-lead ECG tracing. Significantly fewer still (27%) would make the diagnosis based on PPG-based tracing. Wearable ECG technology is acceptable for the majority of respondents for screening, diagnostics, monitoring, and follow-up of arrhythmia patients, while respondents were more reluctant to use PPG technology for these indications. Most respondents (74%) would advocate systematic screening for AF using wearable rhythm devices, starting at patients' median age of 60 (IQR 50-65) years. Thirty-six percent of respondents stated that there is no reimbursement for diagnostics involving wearable rhythm devices in their countries. Most respondents (56.4%) believe that costs of wearable rhythm devices should be shared between patients and insurances. Wearable single- or multiple-lead ECG technology is accepted for multiple indications in current clinical practice and triggers AF diagnosis and treatment. The unmet needs that call for action are reimbursement plans and integration of wearable rhythm device data into patient's files and hospital information systems.

Utilization and perception of same-day discharge in electrophysiological procedures and device implantations: an EHRA survey.

The aim of this European Heart Rhythm Association (EHRA) survey was to assess the utilization of same-day discharge (SDD) in electrophysiology (EP). An online-based questionnaire was shared with the EHRA community between 12 and 30 June 2020 and recorded institutional information, complication assessment, recent experiences, and opinions regarding possible advantages or concerns with SDD. In total, 218 responses from 49 countries provided information on current SDD management. Overall, SDD was implemented in 77.5%, whereas this proportion was significantly higher in tertiary and high-volume centres (83.8% and 85.3%, both P < 0.01). The concept of SDD was most commonly used following implantations of cardiac event recorders (97%), diagnostic EP procedures (72.2%), and implantations of pacemakers with one or two intracardiac leads (50%), while the lowest SDD utilization was observed after catheter ablations of left atrial or ventricular arrhythmias. Within SDD-experienced centres, ∼90% respondents stated that this discharge concept is recommendable or highly recommendable and reported that rates of increased rehospitalization and complication rates were low. Most respondents assumed a better utilization of hospital resources (78.2%), better cost effectiveness (77.3%), and an improved patients' comfort but were concerned about possible impairment of detection (72.5%) and management (78.7%) of late complications. In conclusion, >75% of respondents already implement SDD following EP interventions with a large heterogeneity with regard to specific procedures. Further research is needed to confirm or disprove existing and expected benefits and obstacles.

Reprocessing of electrophysiology material in EHRA countries: an EHRA Young EP survey.

Data on reprocessing of electrophysiology (EP) materials are sparse. Reprocessing of catheters and other materials in daily routine varies through countries and may depend on specific material characteristics, supplier, or federal law. The aim of this study was to collect data on reprocessing usage through EHRA countries. An online survey consisting of 27 questions was distributed to EHRA Young EP members and members of national EP working groups. Two hundred and two participants from 34 EHRA countries completed the survey. One hundred and seven respondents (53.0%) reported having used and using reprocessed EP material, 30 (14.9%) respondents have used reprocessed EP material in the past but not at the time of the survey, 65 (32.2%) had never used reprocessed EP material. The most reprocessed EP materials include cables (70%), diagnostic EP catheters with deflectable (64%) or fixed curve (63%), non-irrigated ablation catheters (51%), and other conventional diagnostic catheters (41%). The most durable material was diagnostic EP catheters with a fixed curve (61%), the most sensitive material was ablation catheters with contact force sensors (21%). Important benefits were seen in reducing costs for the providing hospital (65%) and the healthcare provider (42%) and making EP procedures available for a greater number of patients (42%). Main concerns were on quality aspects (58%), contamination (52%), and loss of precision (47%). Reprocessing of EP materials is heterogeneously managed among EHRA countries. The present survey shows that European electrophysiologists consider the use of reprocessed EP material as generally safe and cost-effective.

Role of wearable rhythm recordings in clinical decision making-The wEHRAbles project.

BACKGROUND: Multiple wearable devices for rhythm analysis have been developed using either photoplethysmography (PPG) or handheld ECG. HYPOTHESIS: The aim of this survey was to assess impact of these technologies on physicians' clinical decision-making regarding initiation of diagnostic steps, drug therapy, and invasive strategies. METHODS: The online survey included 10 questions on types of devices, advantages, and disadvantages of wearable devices as well as case scenarios for patients with supraventricular arrhythmias and atrial fibrillation (AF). RESULTS: A total of 417 physicians (median age 37 [IQR 32-43] years) from 42 countries world-wide completed the survey. When presented a tracing of a regular tachycardia by a symptomatic patient, most participants would trigger further diagnostic steps (90% for single-lead ECG vs 83% for PPG, P < .001), while a single-lead ECG would be sufficient to perform an invasive EP study in approximately half of participants (51% vs 22% for PPG, P < .001). When presented with a single-lead ECG tracing suggesting AF, most participants (90%) would trigger further diagnostic steps. A symptomatic AF patient would trigger anticoagulation treatment to a higher extent as an asymptomatic patient (59% vs 21%, P < .001). PPG tracings would only rarely lead to therapeutic steps regardless of symptoms. Most participants would like scientific society recommendations on the use of wearable devices (62%). CONCLUSIONS: Tracings from wearable rhythm devices suggestive of arrhythmias are most likely to trigger further diagnostic steps, and in the case of PPG recordings rarely therapeutic interventions. A majority of participants expect these devices to facilitate diagnostics and arrhythmia screening but fear data overload and expect scientific society recommendations on the use of wearables.

Performance of handheld electrocardiogram devices to detect atrial fibrillation in a cardiology and geriatric ward setting.

AIMS: To determine the usability, accuracy, and cost-effectiveness of two handheld single-lead electrocardiogram (ECG) devices for atrial fibrillation (AF) screening in a hospital population with an increased risk for AF. METHODS AND RESULTS: Hospitalized patients (n = 445) at cardiological or geriatric wards were screened for AF by two handheld ECG devices (MyDiagnostick and AliveCor). The performance of the automated algorithm of each device was evaluated against a full 12-lead or 6-lead ECG recording. All ECGs and monitor tracings were also independently reviewed in a blinded fashion by two electrophysiologists. Time investments by nurses and physicians were tracked and used to estimate cost-effectiveness of different screening strategies. Handheld recordings were not possible in 7 and 21.4% of cardiology and geriatric patients, respectively, because they were not able to hold the devices properly. Even after the exclusion of patients with an implanted device, sensitivity and specificity of the automated algorithms were suboptimal (Cardiology: 81.8 and 94.2%, respectively, for MyDiagnostick; 54.5 and 97.5%, respectively, for AliveCor; Geriatrics: 89.5 and 95.7%, respectively, for MyDiagnostick; 78.9 and 97.9%, respectively, for AliveCor). A scenario based on automated AliveCor evaluation in patients without AF history and without an implanted device proved to be the most cost-effective method, with a provider cost to identify one new AF patient of €193 and €82 at cardiology and geriatrics, respectively. The cost to detect one preventable stroke per year would be €7535 and €1916, respectively (based on average CHA2DS2-VASc of 3.9 ± 2.0 and 5.0 ± 1.5, respectively). Manual interpretation increases sensitivity, but decreases specificity, doubling the cost per detected patient, but remains cheaper than sole 12-lead ECG screening. CONCLUSION: Using AliveCor or MyDiagnostick handheld recorders requires a structured screening strategy to be effective and cost-effective in a hospital setting. It must exclude patients with implanted devices and known AF, and requires targeted additional 12-lead ECGs to optimize specificity. Under these circumstances, the expenses per diagnosed new AF patient and preventable stroke are reasonable.

Long-Term Performance of the Riata/ST Implantable Cardioverter-Defibrillator Lead.

Riata and Riata ST implantable cardioverter-defibrillator leads are prone to structural and electrical failure (EF). Our objective was to evaluate Riata/ST lead performance over a long-term follow-up. Of 184 patients having undergone Riata/ST and Riata ST Optim lead implantation from September 2003 to June 2008, 154 patients were evaluated for EF and radiographic conductor externalization (CE). Survival analysis for EF was performed for Riata/ST leads, both for failure-free lead survival and cumulative hazard. Subanalysis on 7Fr leads was performed to evaluate EF and CE rates both for different Riata ST lead management (monitoring vs proactive) and between Riata ST and Riata ST Optim leads. During a mean follow-up of 7 years, Riata/ST lead EF rate was 13% overall. Similar failure-free survival rate was noted for 7Fr as for 8Fr leads (log-rank, p = 0.63). Of all failed leads, 64% failed only after 5 years of follow-up. Compared with the absolute failure rate of 1.84% per device year, cumulative hazard analysis for leads surviving past 5 years revealed an estimated failure rate of 7% per year. No clinical or procedural predictors for EF were found. The subanalysis on 7Fr leads showed an excellent outcome both for a proactive lead management approach as for Optim leads. In conclusion, long-term survival of the Riata/ST lead is impaired with an accelerating EF risk over time. An initial exponential trend was followed by a linear lead failure pattern for leads surviving past 5 years, corresponding to an estimated 7% annual EF rate. These findings may have repercussions on the lead management strategy in patients currently surviving with a Riata/ST lead to prevent significant clinical events like inappropriate shocks or failed device interventions.

Lessons Learned from Asymptomatic Acute Coronary Occlusion Complicating Radiofrequency Ablation of Right Ventricular Outflow Tract Tachycardia.

INTRODUCTION: Radiofrequency ablation has become a standard procedure in the treatment of ventricular arrhythmias. The success rate varies according to the etiology and the presence or absence of underlying structural heart disease, while complication rates are relatively low. METHODS: To describe the damage in neighboring structures during the ablation in certain locations. RESULTS: We present a patient who underwent a radiofrequency ablation of sustained monomorphic ventricular tachycadia at the inferior and anterior part of the right ventricular outflow tract, at the insertion of the right ventricle to the left ventricle. Extensive ablation resulted in an asymptomatic occlusion of the mid segment of the left descending coronary artery. CONCLUSION: Creation of deeper and broader lesions with current catheter technologies can result in damage of the adjacent endo- and epicardial structures. Careful evaluation of the area of interest prior to and after the ablation should therefore be mandatory.

Is recent cannabis use associated with acute coronary syndromes? An illustrative case series.

Cannabis is a frequently used recreational drug that potentially imposes serious health problems. We report three cases where recent and/or chronic use of marijuana led to severe cardiac dysfunction. All three patients collapsed at home and required cardiopulmonary resuscitation (CPR) with initial restoration of spontaneous circulation (ROSC). The mechanism of the cardiovascular collapse was different in each case. The first case presented with asystole and was found to have diffuse coronary vasospasm on coronary angiography in the hours after acute cannabis abuse. In the second case, an acute anterior infarction with occlusion of both the right coronary artery (RCA) and the left anterior descendens (LAD) was observed in a young patient without known cardiovascular risks but with chronic cannabis abuse. The third case presented at home with ventricular fibrillation presumably caused by an acute coronary syndrome due to left anterior descending (LAD) artery occlusion. The hetero-anamnesis of the family reported that all three patients had recently used cannabis. Toxicological screening also showed no other substance abuse than cannabis. Using these three cases, we would like to illustrate that the widespread use of cannabis is not as innocent as is believed. Cannabis use can lead to severe cardiovascular problems and sudden death, not only in people at increased cardiovascular risk, but also in young people without any medical history or risk factors.