Publications by authors named "Ardan M Saguner"

136 Publications

Sex differences and adherence of patients treated with wearable cardioverter-defibrillator: insights from an international multicenter register.

J Cardiovasc Electrophysiol 2022 Aug 5. Epub 2022 Aug 5.

Department of Cardiology, Angiology, Haemostaseology and Medical Intensive Care, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Germany.

Aims: Treatment with the wearable cardioverter defibrillator (WCD) may protect against sudden cardiac death (SCD) as a bridging therapy until a cardioverter-defibrillator may be implanted. We analyzed in a multicenter setting a consecutive patient cohort wearing WCD to explore sex differences.

Methods And Results: We analyzed 708 consecutive patients, 579 (81.8%) from whom were males and 129 (18.2%) females (age, 60.5±14 vs. 61.6±17 years old; p=0.44). While the rate of ischemic cardiomyopathy (ICM) as a cause of prescription of WCD was significantly higher in males as compared to females (42.7% vs. 26.4%; p=0.001), females received it more frequently due to non-ischemic cardiomyopathy (NICM) (55.8% vs. 42.7%); p=0.009). The wear time of WCD was equivalent in both groups (21.1±4.3 hours/days in males vs. 21.5±4.4 hours/days in females; p=0.27; and 62.6±44.3 days in males vs. 56.5±39 days in females; p=0.15). Mortality was comparable in both groups at 2-year-follow-up (6.8% in males vs. 9.7% in females; p=0.55). Appropriate WCD shocks and the incidence of ICD implantations were similar in both groups (2.4% in males vs. 3.9% in females; p=0.07) (35.1% in males vs. 31.8% in females; p=0.37), respectively. In age tertile analysis, compliance was observed more in 73-91 years old group as compared to 14-51 years old group (87.8% vs. 68.3%; p<0.001).

Conclusion: Compliance for wearing WCD was excellent regardless of sex. Furthermore, mortality and the incidence of ICD implantations were comparable in both sexes. Appropriate WCD shocks were similar in both sexes. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/jce.15648DOI Listing
August 2022

Atrial cardiomyopathy: from cell to bedside.

ESC Heart Fail 2022 Aug 3. Epub 2022 Aug 3.

Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Atrial cardiomyopathy refers to structural and electrical remodelling of the atria, which can lead to impaired mechanical function. While historical studies have implicated atrial fibrillation as the leading cause of cardioembolic stroke, atrial cardiomyopathy may be an important, underestimated contributor. To date, the relationship between atrial cardiomyopathy, atrial fibrillation, and cardioembolic stroke remains obscure. This review summarizes the pathogenesis of atrial cardiomyopathy, with a special focus on neurohormonal and inflammatory mechanisms, as well as the role of adipose tissue, especially epicardial fat in atrial remodelling. It reviews the current evidence implicating atrial cardiomyopathy as a cause of embolic stroke, with atrial fibrillation as a lagging marker of an increased thrombogenic atrial substrate. Finally, it discusses the potential of antithrombotic therapy in embolic stroke with undetermined source and appraises the available diagnostic techniques for atrial cardiomyopathy, including imaging techniques such as echocardiography, computed tomography, and magnetic resonance imaging as well as electroanatomic mapping, electrocardiogram, biomarkers, and genetic testing. More prospective studies are needed to define the relationship between atrial cardiomyopathy, atrial fibrillation, and embolic stroke and to establish a prompt diagnosis and specific treatment strategies in these patients with atrial cardiomyopathy for the secondary and even primary prevention of embolic stroke.
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http://dx.doi.org/10.1002/ehf2.14089DOI Listing
August 2022

Novel Risk Prediction Model to Determine Adverse Heart Failure Outcomes in Arrhythmogenic Right Ventricular Cardiomyopathy.

J Am Heart Assoc 2022 Jul 29;11(13):e024634. Epub 2022 Jun 29.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.

Background Patients with arrhythmogenic right ventricular cardiomyopathy are at risk for life-threatening ventricular tachyarrhythmias, but progressive heart failure (HF) may occur in later stages of disease. This study aimed to characterize potential risk predictors and develop a model for individualized assessment of adverse HF outcomes in arrhythmogenic right ventricular cardiomyopathy. Methods and Results Longitudinal and observational cohorts with 290 patients with arrhythmogenic right ventricular cardiomyopathy from the Fuwai Hospital in Beijing, China, and 99 patients from the University Heart Center in Zurich, Switzerland, with follow-up data were studied. The primary end point of the study was heart transplantation or death attributable to HF. The model was developed by Cox regression analysis for predicting risk and was internally validated. During 4.92±3.03 years of follow-up, 48 patients reached the primary end point. The determinants of the risk prediction model were left ventricular ejection fraction, serum creatinine levels, moderate-to-severe tricuspid regurgitation, and atrial fibrillation. Implantable cardioverter-defibrillators did not reduce the occurrence of adverse HF outcomes. Conclusions A novel risk prediction model for arrhythmogenic right ventricular cardiomyopathy has been developed using 2 large and well-established cohorts, incorporating common clinical parameters such as left ventricular ejection fraction, serum creatinine levels, tricuspid regurgitation, and atrial fibrillation, which can identify patients who are at risk for terminal HF events, and may guide physicians to assess individualized HF risk and to optimize management strategies.
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http://dx.doi.org/10.1161/JAHA.121.024634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333366PMC
July 2022

Clinical impact of low coverage in whole-exome genetic testing in the assessment of familial arrhythmogenic right ventricular cardiomyopathy: a case report.

Eur Heart J Case Rep 2021 Jun 17;5(6):ytab111. Epub 2021 Jun 17.

Department of Cardiology, University Heart Center Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited condition, with approximately 60% of patients carrying a possibly disease-causing genetic variant. Known desmosomal genes account for about 50% of those variants. We herein report a family with ARVC in which a pathogenic desmosomal variant was missed because of the initial genetic testing method.

Case Summary: A 54-year-old man diagnosed with ARVC underwent genetic cascade screening for a heterozygous titin variant (: c.26542C>T), detected in his phenotypically affected sister. He did not harbour this variant. Moreover, reclassification of this variant based on the American College of Medical Genetics (ACMG) 2015 criteria showed it to be likely benign. Upon genetic re-screening with a dedicated cardiomyopathy panel a heterozygous missense variant in desmoglein-2 (: c.152G>C) was found. His sister's DNA was re-analysed and the same variant was detected, and classified as LP (likely pathogenic) by current literature.

Discussion: The initial genetic screening tool used in the patient's sister (whole-exome sequencing, WES) failed to detect the likely causative desmosomal variant in our family. While WES represents a good tool in searching for novel genes in Trio Analysis, it has a low DNA coverage in important regions (mean 10×) of known ARVC-associated genes. We therefore propose using smaller panels with better coverage in the clinical setting, such as Trusight-cardio (mean DNA coverage 100-300×) as an initial genetic screening method.
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http://dx.doi.org/10.1093/ehjcr/ytab111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274652PMC
June 2021

Treatment Planning for Cardiac Radioablation: Multicenter Multiplatform Benchmarking for the XXX Trial.

Int J Radiat Oncol Biol Phys 2022 Jun 15. Epub 2022 Jun 15.

Klinik für Radioonkologie und Strahlentherapie, Charité - Universitätsmedizin Berlin, Berlin, Germany. Electronic address:

Purpose: Cardiac radioablation is a novel treatment option for patients with refractory ventricular tachycardia (VT) unsuitable for catheter ablation. The quality of treatment planning depends on dose specifications, platform capabilities, and experience of the treating staff. To harmonize the treatment planning, benchmarking of this process is necessary for multicenter clinical studies such as the XXX trial.

Methods And Materials: Planning computed tomography data and consensus structures from three patients were sent to five academic centers for independent plan development using a variety of platforms and techniques with the XXX study protocol serving as guideline. Three-dimensional dose distributions and treatment plan details were collected and analyzed. In addition, an objective relative plan quality ranking system for VT treatments was established.

Results: For each case, three coplanar volumetric modulated arc (VMAT) plans for C-arm linear accelerators (LINAC) and three non-coplanar treatment plans for robotic arm LINAC were generated. All plans were suitable for clinical applications with minor deviations from study guidelines in most centers. Eleven of 18 treatment plans showed maximal one minor deviation each for target and cardiac substructures. However, dose-volume histograms showed substantial differences: in one case, the PTV≥30Gy ranged from 0.0% to 79.9% and the RIVA V ranged from 4.0% to 45.4%. Overall, the VMAT plans had steeper dose gradients in the high dose region, while the plans for the robotic arm LINAC had smaller low dose regions. Thereby, VMAT plans required only about half as many monitor units, resulting in shorter delivery times, possibly an important factor in treatment outcome.

Conclusions: Cardiac radioablation is feasible with robotic arm and C-arm LINAC systems with comparable plan quality. Although cross-center training and best practice guidelines have been provided, further recommendations, especially for cardiac substructures, and ranking of dose guidelines will be helpful to optimize cardiac radioablation outcomes.
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http://dx.doi.org/10.1016/j.ijrobp.2022.06.056DOI Listing
June 2022

Right atrial strain and cardiovascular outcome in arrhythmogenic right ventricular cardiomyopathy.

Eur Heart J Cardiovasc Imaging 2022 Jun;23(7):970-978

Department of Cardiology, University Heart Center, University Hospital Zürich, Zurich, Switzerland.

Aims: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive fibro-fatty infiltration of the myocardium and associated with adverse cardiovascular (CV) events. This study aims to examine right atrial (RA) deformation in ARVC and understand its association with CV outcomes.

Methods And Results: RA strain was determined in 50 patients with definite ARVC, compared with a matched control group of 50 healthy individuals, and analysed for outcome association over a median follow-up duration of 5 years. A subgroup of 30 ARVC patients with normal RA volume (ARVC-N group) was compared with 30 matched controls (Control-N), and the outcome was analysed separately. RA reservoir, conduit, and pump strain were significantly impaired in ARVC vs. control. Similar observations were made in the N-ARVC subgroup. Reservoir strain was associated with an increased risk of atrial arrhythmia (AA) [hazard ratio (HR) 0.88, P < 0.01] and CV events (HR 0.92, P < 0.01). Conduit strain also predicted AA (HR 1.02, P < 0.01), while pump strain predicted CV events (HR 1.09, P = 0.02). Reservoir strain improved the fitness of bivariable models for the association of RV end-diastolic area index, RV fractional area change, and RV global longitudinal strain with CV events.

Conclusion: ARVC patients display impaired RA strain even when RA volume is normal. Reservoir and pump strain are associated with an increased risk of CV events. Reservoir strain improved model fitness for the association of RVGLS and other echocardiographic parameters with CV events.
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http://dx.doi.org/10.1093/ehjci/jeac070DOI Listing
June 2022

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

Eur Heart J 2022 Apr 20. Epub 2022 Apr 20.

Department of Genetics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, Groningen, The Netherlands.

Aims: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients.

Methods And Results: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001).

Conclusion: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).
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http://dx.doi.org/10.1093/eurheartj/ehac180DOI Listing
April 2022

Predictors of left atrial fibrosis in patients with atrial fibrillation referred for catheter ablation.

Cardiol J 2022 14;29(3):413-422. Epub 2022 Mar 14.

Department of Cardiology, University Heart Center, University Hospital Zurich, Switzerland.

Background: Left atrial (LA) fibrosis in patients with atrial fibrillation (AF) is associated with an increased risk of AF recurrence after catheter ablation. Therefore, we searched for clinical risk factors that confer an increased risk of LA fibrosis, which can influence the treatment strategy.

Methods: We included 94 patients undergoing 3-dimensional electroanatomical voltage mapping-guided catheter ablation of AF. LA low-voltage areas during sinus rhythm as a surrogate parameter of fibrosis were measured with the CARTO3 mapping system and adjusted for LA volumes obtained by computed tomography. Blood tests including N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and echocardiographic parameters of left ventricular function were also analyzed.

Results: Patients were 62.5 ± 11.4 years old, and 29% were female. LA fibrosis was present in 65%, with 50% having a fibrotic area > 5% (≥ Utah-Stage 1). Mean left ventricular ejection fraction (LVEF) was 53.9 ± 10.5%. Patients with LA fibrosis had higher NT-proBNP levels (869 ± 1056 vs. 552 ± 859 ng/L, p = 0.001) and larger LA volumes (body surface area-corrected 63.3 ± 19.3 vs. 80 ± 27.1 mL/m2, p = 0.003). In univariable analyses, LA fibrosis was significantly associated with female gender, older age, increased LA volumes, hypertension, statin therapy, higher NT-proBNP values, and echocardiographic E/e'. In bivariable analyses, higher NT-proBNP, echocardiographic parameters of diastolic dysfunction, female gender, older age, and higher DR-FLASH scores remained as independent predictors of LA fibrosis.

Conclusions: In this single-center longitudinal study, surrogate parameters of elevated left-sided cardiac filling pressures such as higher NT-proBNP levels and higher echocardiographic E/e' values as well as female gender independently predicted the prevalence of LA fibrosis in patients referred for catheter ablation of AF.
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http://dx.doi.org/10.5603/CJ.a2022.0012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170329PMC
June 2022

Benefits and outcomes of a new multidisciplinary approach for the management and financing of sudden unexplained death cases in a forensic setting in Switzerland.

Forensic Sci Int 2022 May 25;334:111240. Epub 2022 Feb 25.

Zurich Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland. Electronic address:

Sudden cardiac death (SCD) is an important public health issue. In young persons aged between 1 and 40 years, most SCDs are caused by potentially inherited cardiac diseases, often not detectable during conventional medico-legal investigations and therefore termed as sudden unexplained deaths (SUD). In this study, we describe the implementation, feasibility and importance of a standardized procedure to investigate SUD cases within the forensic framework at the Zurich Institute of Forensic Medicine in Switzerland. This new approach involves a multidisciplinary collaboration including forensic autopsy, second pathology expert opinion, post-mortem molecular genetic testing, cardiac counselling of relatives, and a tentative financing. This procedure is in line with the published Swiss and European recommendations on the management of SCDs. During a two-year pilot project, 39 sudden and unexpected death cases were collected, whereof 10 deceased remained without any identifiable cause of death after medico-legal investigation and second expert evaluation. Molecular autopsy, including 393 genes involved in cardio-vascular and metabolic diseases, identified eight pathogenic or likely pathogenic genetic variants in five out of the 10 deceased (50%). Cardio-genetic follow-up investigations in the families of the 10 deceased revealed phenotype-positive relatives in four families and required specific therapies, including an implantable cardioverter defibrillator (ICD) for primary prevention. Multidisciplinary collaboration is crucial for an optimal management of sudden unexplained death cases, to identify additional relatives at risk, and to prevent other tragic deaths within a family.
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http://dx.doi.org/10.1016/j.forsciint.2022.111240DOI Listing
May 2022

Changes in Exercise Capacity and Ventricular Function in Arrhythmogenic Right Ventricular Cardiomyopathy: The Impact of Sports Restriction during Follow-Up.

J Clin Med 2022 Feb 22;11(5). Epub 2022 Feb 22.

Department of Cardiology, University Heart Center Zurich, CH-8091 Zurich, Switzerland.

(1) Background: Physical exercise has been suggested to promote disease progression in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). We aimed to investigate the exercise performance and ventricular function of ARVC patients during follow-up, while taking into account their adherence to exercise restriction recommendations. (2) Methods: This retrospective study included 49 patients (33 male, 67%) who had an exercise test at baseline and after 4.2 ± 1.6 years. Of the 49 ARVC patients, 27 (55%) were athletes, while 22 (45%) were non-athletes. Of the athletes, 12 (44%) continued intensive sports activity (non-adherent), while 15 (56%) stopped intensive physical activity upon recommendation (adherent). The maximum workload in Watts (W), percentage of the target workload (W%), and double product (DP) factor were measured for all patients. (3) Results: The non-adherent cohort had a significant decrease in physical performance (W at baseline vs. follow-up, = 0.012; W% at baseline vs. follow-up, = 0.025; DP-factor at baseline vs. follow-up, = 0.012) over time. Left ventricular (LV) function (LV ejection fraction at baseline vs. follow-up, = 0.082) showed a decreasing trend in the non-adherent cohort, while the performance of the adherent cohort remained at a similar level. (4) Conclusions: If intensive sports activities are not discontinued, exercise capacity and left ventricular function of athletes with ARVC deteriorates during follow-up. All patients with ARVC need to strictly adhere to the recommendation to cease intense sports activity in order to halt disease progression.
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http://dx.doi.org/10.3390/jcm11051150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911196PMC
February 2022

Phrenic Nerve Injury During Cryoballoon-Based Pulmonary Vein Isolation: Results of the Worldwide YETI Registry.

Circ Arrhythm Electrophysiol 2022 01 28;15(1):e010516. Epub 2021 Dec 28.

Arrhythmia and Electrophysiology Unit, Department of Cardiology, Hacettepe University, Ankara, Turkey (K.A.).

Background: Cryoballoon-based pulmonary vein isolation (PVI) has emerged as an effective treatment for atrial fibrillation. The most frequent complication during cryoballoon-based PVI is phrenic nerve injury (PNI). However, data on PNI are scarce.

Methods: The YETI registry is a retrospective, multicenter, and multinational registry evaluating the incidence, characteristics, prognostic factors for PNI recovery and follow-up data of patients with PNI during cryoballoon-based PVI. Experienced electrophysiological centers were invited to participate. All patients with PNI during CB2 or third (CB3) and fourth-generation cryoballoon (CB4)-based PVI were eligible.

Results: A total of 17 356 patients underwent cryoballoon-based PVI in 33 centers from 10 countries. A total of 731 (4.2%) patients experienced PNI. The mean time to PNI was 127.7±50.4 seconds, and the mean temperature at the time of PNI was -49±8°C. At the end of the procedure, PNI recovered in 394/731 patients (53.9%). Recovery of PNI at 12 months of follow-up was found in 97.0% of patients (682/703, with 28 patients lost to follow-up). A total of 16/703 (2.3%) reported symptomatic PNI. Only 0.06% of the overall population showed symptomatic and permanent PNI. Prognostic factors improving PNI recovery are immediate stop at PNI by double-stop technique and utilization of a bonus-freeze protocol. Age, cryoballoon temperature at PNI, and compound motor action potential amplitude loss >30% were identified as factors decreasing PNI recovery. Based on these parameters, a score was calculated. The YETI score has a numerical value that will directly represent the probability of a specific patient of recovering from PNI within 12 months.

Conclusions: The incidence of PNI during cryoballoon-based PVI was 4.2%. Overall 97% of PNI recovered within 12 months. Symptomatic and permanent PNI is exceedingly rare in patients after cryoballoon-based PVI. The YETI score estimates the prognosis after iatrogenic cryoballoon-derived PNI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03645577. Graphic Abstract: A graphic abstract is available for this article.
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http://dx.doi.org/10.1161/CIRCEP.121.010516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772436PMC
January 2022

Wearable Cardioverter-Defibrillator-Measured Step Count for the Surveillance of Physical Fitness during Cardiac Rehabilitation.

Sensors (Basel) 2021 Oct 25;21(21). Epub 2021 Oct 25.

Department of Cardiology, University Heart Center Zurich, 8091 Zurich, Switzerland.

Background: The wearable cardioverter-defibrillator (WCD) has a built-in accelerometer, which allows tracking of patients' physical activity by remote monitoring. It is unclear whether WCD-measured physical activity, step count, and heart rate correlate with established tools for the assessment of cardiopulmonary fitness such as the 6-min walk test (6MWT).

Objective: To correlate measurements of patient physical activity through the WCD with a supervised 6MWT during in-patient cardiac rehabilitation (CR) and to allow their use as surrogate parameters of cardiopulmonary fitness in an out-patient setting.

Methods: Consecutive patients with a history of WCD use treated at our center and an in-patient CR following an index hospitalization were included. Baseline characteristics, measurements of WCD accelerometer (median daily step count, median daily activity level), median daily heart rate, and clinically supervised 6MWT at admission and discharge of CR were obtained.

Results: Forty-one patients with a mean age of 55.5 (±11.5) years were included. Thirty-five patients (85.4%) were male and 28 patients (68%) had a primary prophylactic WCD-indication. The most common underlying heart diseases were ischemic heart disease (24 patients 58.6%) and dilated cardiomyopathy (13 patients, 31.7%). Median CR duration was 20 (IQR 19.75-26.25) days. 6MWT distance increased from a mean of 329 m (±107) to 470 m (±116) during CR ( < 0.0001). The median daily step count and activity level increased significantly, from 5542 steps (IQR 3718-7055) to 8778 (IQR 6229-12,920, < 0.0001) and median 117 10 (IQR 96 10-142 10) threshold value exceedance (TVE) to 146 10 TVE (IQR 110 × 10-169 × 10, < 0.0001), respectively. The median heart rate was 74.9 bpm (IQR 65.8-84.5) and 70.2 (IQR 64.1-77.3, = 0.09) at admission and discharge, respectively. Of all three parameters, median daily step count showed the best correlation to the results of the 6MWT at admission and discharge (r = 0.32, = 0.04 and 0.37, = 0.02, respectively).

Conclusions: Remote monitoring of median daily step count as assessed by the WCD's accelerometer showed positive correlation with the 6MWT and could serve as a surrogate for cardiopulmonary exercise capacity. Assessment of daily step count and activity level measured remotely by the WCD could help to tailor optimal exercise instruction for patients not attending CR.
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http://dx.doi.org/10.3390/s21217054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588232PMC
October 2021

Efficacy of Catheter Ablation for Atrial Arrhythmias in Patients with Arrhythmogenic Right Ventricular Cardiomyopathy-A Multicenter Study.

J Clin Med 2021 Oct 26;10(21). Epub 2021 Oct 26.

Department of Cardiology, University Heart Center, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.

Atrial arrhythmias are present in up to 20% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Catheter ablation (CA) is an effective treatment for atrial arrhythmias in the general population. Data regarding CA for atrial arrhythmias in ARVC are scarce. : To assess the safety and efficacy of CA for atrial arrhythmias in patients with ARVC. In this international collaborative effort, all patients with a definite diagnosis of ARVC undergoing CA for atrial fibrillation (AF), focal atrial tachycardia (AT), or cavotricuspid isthmus (CTI)-dependent atrial flutter (AFl) were extracted from twelve ARVC registries. Demographic, periprocedural, and long-term arrhythmic outcome data were collected. Thirty-seven patients were enrolled in the study (age 50.2 ± 16.6 years, male 84%, CHADSVASc 1 (1,2), HAS-BLED 0 (0-2)). The arrhythmia leading to CA was AF in 23 (62%), focal left AT in 5 (14%), and CTI-dependent AFl in 9 (24%). Acute procedural success was achieved in all procedures but one ( = 1 focal left AT; 97% acute success). The median follow-up period was 27 (13-67) months, and 96%, 74%, and 61% of patients undergoing AF ablation were free from any atrial arrhythmia recurrence after a single procedure at 6 months, 12 months, and last follow-up, respectively. After focal AT ablation, freedom from atrial arrhythmia recurrence was 80%, 80%, and 60% at 6 months, 12 months, and last follow-up, respectively. All patients undergoing CTI ablation were free from atrial arrhythmia recurrences at 6 months, with 89% single-procedural arrhythmic freedom at last follow-up. One major complication (2.7%; PV stenosis requiring PV stenting) occurred. CA is safe and effective in managing atrial arrhythmias in patients with ARVC, with success rates comparable to the general population.
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http://dx.doi.org/10.3390/jcm10214962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8584554PMC
October 2021

Novel plasma biomarkers predicting biventricular involvement in arrhythmogenic right ventricular cardiomyopathy.

Am Heart J 2022 02 29;244:66-76. Epub 2021 Oct 29.

Department of Cardiology, University Heart Center Zurich, Zurich, Switzerland; Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. Electronic address:

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease characterized by fibrofatty replacement of the myocardium and ventricular arrhythmias. Biventricular involvement in ARVC may lead to heart failure. This study aimed to investigate the role of plasma biomarkers soluble (s)ST2, Galectin-3 (Gal-3) and GDF-15 in predicting biventricular involvement and adverse outcomes in ARVC.

Methods And Results: ARVC patients from 2 independent cohorts, were studied. The Bejing (Chinese) cohort (n = 108) was the discovery cohort, whereas the Zurich (Swiss) cohort (n = 47) served as validation. All patients had a definite ARVC diagnosis at time of blood withdrawal. Biomarkers were independently correlated with NT-proBNP and left ventricular (LV)-function. ARVC patients with LV involvement had higher levels of sST2 and GDF-15 as compared to controls and patients with isolated right ventricle (RV) involvement. sST2 and GDF-15 were significantly correlated with late gadolinium enhancement in CMR and with adverse heart failure outcomes. Gal-3 was elevated in ARVC patients with and without LV involvement. The combined use of the three biomarkers (sST2, GDF-15 and NT-proBNP) showed the best performance in predicting LV involvement in both cohorts. Plasma drawn from the coronary arteries and coronary sinus indicated a transmyocardial elevation of sST2, but no transmyocardial gradient of GDF-15. After heart transplantation, both sST2 and GDF-15 returned to near-normal levels.

Conclusion: Our study showed that sST2 and GDF-15 may predict biventricular involvement in ARVC. The combined use of sST2, GDF-15 and NT-proBNP showed the best prediction of biventricular involvement in ARVC.
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http://dx.doi.org/10.1016/j.ahj.2021.10.187DOI Listing
February 2022

Distinctive characteristics of his bundle potentials in patients with atrioventricular nodal reentrant tachycardia.

Cardiol J 2021 Sep 28. Epub 2021 Sep 28.

Arrhythmia and Electrophysiology, Department of Cardiology, University Heart Center, University Hospital Zurich, Switzerland.

Background: His bundle (HB) potentials vary in amplitude and duration in patients with and without slow pathways. The aim of this study was to determine the characteristics of HB potentials and to elucidate whether they can provide clues for identification of slow pathway (SP).

Methods: The present research prospectively studied the electrophysiological findings of 162 patients with symptomatic atrioventricular nodal reentrant tachycardia (AVNRT) due to slow-fast or fast-slow type and atrioventricular reentrant tachycardia (AVRT). Maximal HB potential (HBmax, HB with the highest amplitude) among HB cloud was recorded in both groups. For AVNRT patients, the following were measured: (1) AH interval at the "jump" during programmed atrial stimulation (A2H2, taken as a reflection of SP conduction time); (2) Distance from HBmax to the successful SP ablation site (HBmax-ABL) and from HBmax to the ostium of coronary sinus (HBmax-CSO).

Results: HBmax was 0.29 ± 0.10 mV in AVNRT patients, whereas it was 0.17 ± 0.05 mV in AVRT group (p < 0.0001). Likewise, the HBmax duration was 22 ± 5 ms in AVNRT group and 16 ± 3 ms in AVRT group (p < 0.0001). The area under the ROC curve of HBmax amplitude in AVNRT patients was 0.86 and the optimal HBmax cut-off to predict AVNRT was ≥ 0.22 mV with a sensitivity of 0.78 and specificity of 0.84. HBmax-CSO was positively correlated with HBmax-ABL, and HBmax-ABL was positively correlated with A2H2.

Conclusions: HBmax amplitudes were higher and durations longer in patients with AVNRT, as compared to those with AVRT. Moreover, the distance between HBmax and successful ablation site was positively correlated with the SP conduction time and with the distance from HBmax to the CS ostium.
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http://dx.doi.org/10.5603/CJ.a2021.0107DOI Listing
September 2021

A Novel Diagnostic Score Integrating Atrial Dimensions to Differentiate between the Athlete's Heart and Arrhythmogenic Right Ventricular Cardiomyopathy.

J Clin Med 2021 Sep 10;10(18). Epub 2021 Sep 10.

Department of Cardiology, University Heart Center Zurich, University Hospital Zurich, 8091 Zurich, Switzerland.

Objective: The 2010 Task Force Criteria (TFC) have not been tested to differentiate ARVC from the athlete's heart. Moreover, some criteria are not available (myocardial biopsy, genetic testing, morphology of ventricular tachycardia) or subject to interobserver variability (right ventricular regional wall motion abnormalities) in clinical practice. We hypothesized that atrial dimensions are useful and robust to differentiate between both entities and proposed a new diagnostic score based upon readily available parameters including echocardiographic atrial dimensions.

Methods: In this observational study, 21 patients with definite ARVC were matched for age, gender and body mass index to 42 athletes. Based on ROC analysis, the following parameters were included in the score: indexed right/left atrial volumes ratio (RAVI/LAVI ratio), NT-proBNP, RVOT measurements (PLAX and PSAX BSA-corrected), tricuspid annular motion (TAM), precordial TWI and depolarization abnormalities according to TFC.

Results: ARVC patients had a higher RAVI/LAVI ratio (1.76 ± 1.5 vs. 0.87 ± 0.2, < 0.001), lower right ventricular function (fac: 29 ± 10.1 vs. 42.2 ± 5%, < 0.001; TAM: 19.8 ± 5.4 vs. 23.8 ± 3.8 mm, = 0.001) and higher serum NT-proBNP levels (345 ± 612 vs. 48 ± 57 ng/L, < 0.001). Our score showed a good performance, which is comparable to the 2010 TFC using those parameters, which are available in routine clinical practice (AUC93%, < 0.001 (95%CI 0.874-0.995) vs. AUC97%, < 0.001 (95%CI 0.93-1.00). A score of 6/12 points yielded a specificity of 91% and an improved sensitivity of 67% for ARVC diagnosis as compared to a sensitivity of 41% for the abovementioned readily available 2010 TFC.

Conclusions: ARVC patients present with significantly larger RA compared to athletes, resulting in a greater RAVI/LAVI ratio. Our novel diagnostic score includes readily available clinical parameters and has a high diagnostic accuracy to differentiate between ARVC and the athlete's heart.
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http://dx.doi.org/10.3390/jcm10184094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472715PMC
September 2021

Preclinical short QT syndrome models: studying the phenotype and drug-screening.

Europace 2022 03;24(3):481-493

University of Mannheim, University of Heidelberg, Germany.

Cardiovascular diseases are the main cause of sudden cardiac death (SCD) in developed and developing countries. Inherited cardiac channelopathies are linked to 5-10% of SCDs, mainly in the young. Short QT syndrome (SQTS) is a rare inherited channelopathy, which leads to both atrial and ventricular tachyarrhythmias, syncope, and even SCD. International European Society of Cardiology guidelines include as diagnostic criteria: (i) QTc ≤ 340 ms on electrocardiogram, (ii) QTc ≤ 360 ms plus one of the follwing, an affected short QT syndrome pathogenic gene mutation, or family history of SQTS, or aborted cardiac arrest, or family history of cardiac arrest in the young. However, further evaluation of the QTc ranges seems to be required, which might be possible by assembling large short QT cohorts and considering genetic screening of the newly described pathogenic mutations. Since the mechanisms underlying the arrhythmogenesis of SQTS is unclear, optimal therapy for SQTS is still lacking. The disease is rare, unclear genotype-phenotype correlations exist in a bevy of cases and the absence of an international short QT registry limit studies on the pathophysiological mechanisms of arrhythmogenesis and therapy of SQTS. This leads to the necessity of experimental models or platforms for studying SQTS. Here, we focus on reviewing preclinical SQTS models and platforms such as animal models, heterologous expression systems, human-induced pluripotent stem cell-derived cardiomyocyte models and computer models as well as three-dimensional engineered heart tissues. We discuss their usefulness for SQTS studies to examine genotype-phenotype associations, uncover disease mechanisms and test drugs. These models might be helpful for providing novel insights into the exact pathophysiological mechanisms of this channelopathy and may offer opportunities to improve the diagnosis and treatment of patients with SQT syndrome.
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http://dx.doi.org/10.1093/europace/euab214DOI Listing
March 2022

High Incidence of Inappropriate Alarms in Patients with Wearable Cardioverter-Defibrillators: Findings from the Swiss WCD Registry.

J Clin Med 2021 Aug 25;10(17). Epub 2021 Aug 25.

Department of Cardiology, University Heart Center Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.

Background: The wearable cardioverter defibrillator (WCD) uses surface electrodes to detect arrhythmia before initiating a treatment sequence. However, it is also prone to inappropriate detection due to artefacts.

Objective: The aim of this study is to assess the alarm burden in patients and its impact on clinical outcomes.

Methods: Patients from the nationwide Swiss WCD Registry were included. Clinical characteristics and data were obtained from the WCDs. Arrhythmia recordings ≥30 s in length were analysed and categorized as VT/VF, atrial fibrillation (AF), supraventricular tachycardia (SVT) or artefact.

Results: A total of 10653 device alarms were documented in 324 of 456 patients (71.1%) over a mean WCD wear-time of 2.0 ± 1.6 months. Episode duration was 30 s or more in 2996 alarms (28.2%). One hundred and eleven (3.7%) were VT/VF episodes. The remaining recordings were inappropriate detections (2736 (91%) due to artefacts; 117 (3.7%) AF; 48 (1.6%) SVT). Two-hundred and seven patients (45%) had three or more alarms per month. Obesity was significantly associated with three or more alarms per month ( = 0.01, 27.7% vs. 15.9%). High alarm burden was not associated with a lower average daily wear time (20.8 h vs. 20.7 h, = 0.785) or a decreased implantable cardioverter defibrillator implantation rate after stopping WCD use (48% vs. 47.3%, = 0.156).

Conclusions: In patients using WCDs, alarms emitted by the device and impending inappropriate shocks were frequent and most commonly caused by artefacts. A high alarm burden was associated with obesity but did not lead to a decreased adherence.
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http://dx.doi.org/10.3390/jcm10173811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432131PMC
August 2021

[CME-EKG 69/Answers: Sinus Pauses in Long-Term Monitoring].

Praxis (Bern 1994) 2021 Sep;110(11):621-624

Klinik für Kardiologie, Universitäres Herzzentrum, Universitätsspital Zürich, Zürich.

CME-EKG 69/Answers: Sinus Pauses in Long-Term Monitoring While the indication for a pacemaker therapy in patients with high-degree AV block or symptomatic bradycardias is straightforward in most cases, intermittent oligo- and asymptomatic sinus bradycardias and pauses turn out to be more challenging. In this case report potential causes, diagnostic steps and possible therapies will be discussed.
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http://dx.doi.org/10.1024/1661-8157/a003731DOI Listing
September 2021

Recommendations regarding cardiac stereotactic body radiotherapy for treatment refractory ventricular tachycardia.

Heart Rhythm 2021 12 8;18(12):2137-2145. Epub 2021 Aug 8.

Department of Internal Medicine III, Section for Electrophysiology und Rhythmology, University Hospital Schleswig-Holstein, Kiel, Germany.

Background: Ventricular tachycardia (VT) is a potentially lethal complication of structural heart disease. Despite optimal management, a subgroup of patients continue to suffer from recurrent VT. Recently, cardiac stereotactic body radiotherapy (CSBRT) has been introduced as a treatment option in patients with VT refractory to antiarrhythmic drugs and catheter ablation.

Objective: The purpose of this study was to establish an expert consensus regarding the conduct and use of CSBRT for refractory VT.

Methods: We conducted a modified Delphi process. Thirteen experts from institutions from Germany and Switzerland participated in the modified Delphi process. Statements regarding the following topics were generated: treatment setting, institutional expertise and technical requirements, patient selection, target volume definition, and monitoring during and after CSBRT. Agreement was rated on a 5-point Likert scale. The strength of agreement was classified as strong agreement (≥80%), moderate agreement (≥66%) or no agreement (<66%).

Results: There was strong agreement regarding the experimental status of the procedure and the preference for treatment in clinical trials. CSBRT should be conducted at specialized centers with a strong expertise in the management of patients with ventricular arrhythmias and in stereotactic body radiotherapy for moving targets. CSBRT should be restricted to patients with refractory VT with optimal antiarrhythmic medication who underwent prior catheter ablation or have contraindications. Target volume delineation for CSBRT is complex. Therefore, interdisciplinary processes that should include cardiology/electrophysiology and radiation oncology as well as medical physics, radiology, and nuclear medicine are needed. Optimal follow-up is required.

Conclusion: Prospective trials and pooled registries are needed to gain further insight into this promising treatment option for patients with refractory VT.
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http://dx.doi.org/10.1016/j.hrthm.2021.08.004DOI Listing
December 2021

[CME-EKG 69: Sinus Pauses in Long-Term Monitoring].

Praxis (Bern 1994) 2021 Aug;110(10):555-560

Klinik für Kardiologie, Universitäres Herzzentrum, Universitätsspital Zürich, Zürich.

CME-EKG 69: Sinus Pauses in Long-Term Monitoring While the indication for a pacemaker therapy in patients with high-degree AV block or symptomatic bradycardias is straightforward in most cases, intermittent oligo- and asymptomatic sinus bradycardias and pauses turn out to be more challenging. In this case report potential causes, diagnostic steps and possible therapies will be discussed.
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http://dx.doi.org/10.1024/1661-8157/a003730DOI Listing
August 2021

Stereotactic radioablation of ventricular arrhythmias in patients with structural heart disease - A systematic review.

Radiother Oncol 2021 09 4;162:132-139. Epub 2021 Jul 4.

Department of Cardiology, University Hospital Zurich, Switzerland. Electronic address:

Background And Purpose: Several studies have suggested stereotactic arrhythmia radioablation (STAR) as a treatment option for patients suffering from therapy-refractory ventricular tachycardia or fibrillation (VT/VF).

Material And Methods: We performed a systematic review of human reports of STAR for structural VT/VF to assess its effectivity and safety. All identified publications were assessed for inclusion. This study adheres to the PRISMA guidelines and was registered on PROSPERO (CRD42020183044).

Results: Thirteen studies were included resulting in a population of 57 patients. Median age was 64 (range 34-83), 31 patients (54%) had ischemic cardiomyopathy and 50 patients (88%) had prior catheter ablation (CA) for VT/VF. A mean planned target volume of 64.4 cc (range 3.5-238) with a mean safety margin of 3.3 mm (0-5) was treated with 25 Gy. Immediately following STAR, four patients (7%) experienced an electrical storm. During a mean follow-up duration of 410 days, all patients suffering from sustained VT/VF prior to STAR (n = 55) had a reduction of their sustained VT/VF-burden after STAR, but recurrence occurred in 41 patients (75%) during follow-up. Forty-six patients (81%) had an adverse effect from therapy, but no treatment-related death occurred. Evidence of scar-formation after STAR either by imaging, invasive mapping or histopathology was found in six of nine examined patients (67%).

Conclusion: From the still very limited experience, STAR appears effective and safe in patients with structural heart disease and therapy-refractory sustained VT/VF. It is associated with a significant short-term reduction of sustained VT/VF-burden, but recurrences are common.
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http://dx.doi.org/10.1016/j.radonc.2021.06.036DOI Listing
September 2021

The genetic architecture of Plakophilin 2 cardiomyopathy.

Genet Med 2021 10 12;23(10):1961-1968. Epub 2021 Jun 12.

Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.

Purpose: The genetic architecture of Plakophilin 2 (PKP2) cardiomyopathy can inform our understanding of its variant pathogenicity and protein function.

Methods: We assess the gene-wide and regional association of truncating and missense variants in PKP2 with arrhythmogenic cardiomyopathy (ACM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) specifically. A discovery data set compares genetic testing requisitions to gnomAD. Validation is performed in a rigorously phenotyped definite ARVC cohort and non-ACM individuals in the Geisinger MyCode cohort.

Results: The etiologic fraction (EF) of ACM-related diagnoses from truncating variants in PKP2 is significant (0.85 [0.80,0.88], p < 2 × 10), increases for ARVC specifically (EF = 0.96 [0.94,0.97], p < 2 × 10), and is highest in definite ARVC versus non-ACM individuals (EF = 1.00 [1.00,1.00], p < 2 × 10). Regions of missense variation enriched for ACM probands include known functional domains and the C-terminus, which was not previously known to contain a functional domain. No regional enrichment was identified for truncating variants.

Conclusion: This multicohort evaluation of the genetic architecture of PKP2 demonstrates the specificity of PKP2 truncating variants for ARVC within the ACM disease spectrum. We identify the PKP2 C-terminus as a potential functional domain and find that truncating variants likely cause disease irrespective of transcript position.
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http://dx.doi.org/10.1038/s41436-021-01233-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8486657PMC
October 2021

Left femoral venous access for leadless pacemaker implantation: patient characteristics and outcomes.

Europace 2021 09;23(9):1456-1461

Electrophysiology Division, Department of Cardiology, University Heart Center Zurich, Raemistrasse 100, 8091 Zurich, Switzerland.

Aims: Leadless pacing has become an alternative approach for patients requiring a single-chamber pacemaker. Conventionally, leadless Micra Transcatheter Pacing System (TPS) pacemakers are implanted via a right femoral venous access. However, due to various reasons, a left-sided femoral venous approach may be necessary. We hypothesized that a left-sided femoral venous approach is as safe and effective when compared with a right-sided approach. We assessed indications, procedural characteristics, safety and mid-term outcomes of Micra TPS implantation via a left femoral venous approach when compared with the conventional right-sided approach.

Methods And Results: In this retrospective single-centre analysis, 143 consecutive patients undergoing Micra TPS implantation were included. 87% (125/143) underwent Micra TPS implantation via a right, and 13% (18/143) via a left femoral venous access. The mean age at implantation was 79.8 ± 7.5 years. Acute procedural success, mean procedure and fluoroscopy times as well as device parameters at implantation and follow-up (mean 15 ± 11.5 months) were similar between the two groups. Five major complications (3.5%) were encountered, all using a right-sided approach. After a transfemoral TAVI procedure, left femoral venous access was used in 42% of cases when compared with 8% in the remaining population (P = 0.003).

Conclusions: A left femoral venous access for Micra TPS implantation is safe and effective with an excellent implantation success rate similar to a conventional right femoral venous access without longer implantation and fluoroscopy times. The most frequent reason for choosing left vs. right femoral venous access was a previous transfemoral TAVI procedure.
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http://dx.doi.org/10.1093/europace/euab083DOI Listing
September 2021

[CME ECG 68/Answers: Gender Specificities in Heart Rhythm Disorders].

Praxis (Bern 1994) 2021 ;110(4):189-191

Klinik für Kardiologie, Universitäres Herzzentrum, Universitätsspital Zürich.

CME ECG 68/Answers: Gender Specificities in Heart Rhythm Disorders Sex differences in heart rhythm disorders have been described, especially due to differences of hormone status in women and men. In general, women do have a higher baseline heart rate than men and shorter refractory periods of most structures in the conduction system, except the ventricles. This is particularly apparent in paroxysmal supraventricular tachycardias. The incidence of a dual AV nodal physiology is the same in both sexes. However, an AV-nodal reentry tachycardia is much more frequent in women than in men. The embryonal disposition for an accessory pathway, as well as the resultant AV reentry tachycardia is more common in men than in women. Focal atrial tachycardias do not reveal a clear dominance between the sexes. Knowledge about sex-related differences in heart rhythm disorders are relevant for its diagnostics. Therefore, important aspects will be discussed in this article.
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http://dx.doi.org/10.1024/1661-8157/a003657DOI Listing
March 2021

The Link Between Sex Hormones and Susceptibility to Cardiac Arrhythmias: From Molecular Basis to Clinical Implications.

Front Cardiovasc Med 2021 17;8:644279. Epub 2021 Feb 17.

Arrhythmia and Electrophysiology, Department of Cardiology, University Heart Center, Zurich, Switzerland.

It is well-known that gender is an independent risk factor for some types of cardiac arrhythmias. For example, males have a greater prevalence of atrial fibrillation and the Brugada Syndrome. In contrast, females are at increased risk for the Long QT Syndrome. However, the underlying mechanisms of these gender differences have not been fully identified. Recently, there has been accumulating evidence indicating that sex hormones may have a significant impact on the cardiac rhythm. In this review, we describe in-depth the molecular interactions between sex hormones and the cardiac ion channels, as well as the clinical implications of these interactions on the cardiac conduction system, in order to understand the link between these hormones and the susceptibility to arrhythmias.
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http://dx.doi.org/10.3389/fcvm.2021.644279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925388PMC
February 2021

[CME ECG 68: Gender Specificities in Heart Rhythm Disorders].

Praxis (Bern 1994) 2021 ;110(3):131-139

Klinik für Kardiologie, Universitäres Herzzentrum, Universitätsspital Zürich.

CME ECG 68: Gender Specificities in Heart Rhythm Disorders Sex differences in heart rhythm disorders have been described, especially due to differences of hormone status in women and men. In general, women do have a higher baseline heart rate than men and shorter refractory periods of most structures in the conduction system, except the ventricles. This is particularly apparent in paroxysmal supraventricular tachycardias. The incidence of a dual AV nodal physiology is the same in both sexes. However, an AV-nodal reentry tachycardia is much more frequent in women than in men. The embryonal disposition for an accessory pathway, as well as the resultant AV reentry tachycardia is more common in men than in women. Focal atrial tachycardias do not reveal a clear dominance between the sexes. Knowledge about sex-related differences in heart rhythm disorders are relevant for its diagnostics. Therefore, important aspects will be discussed in this article.
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http://dx.doi.org/10.1024/1661-8157/a003656DOI Listing
March 2021
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