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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.

Arrhythmogenic cardiomyopathy (ACM) is a familial disease, with approximately 60% of patients displaying a pathogenic variant. The majority of genes linked to ACM code for components of the desmosome: plakophilin-2 (PKP2), desmoglein-2 (DSG2) and desmocollin-2 (DSC2), plakoglobin (JUP) and desmoplakin (DSP). Genetic variants involving the desmosomes are known to cause dysfunction of cell-to-cell adhesions and intercellular gap junctions. In turn, this may result in failure to mechanically hold together the cardiomyocytes, fibrofatty myocardial replacement, cardiac conduction delay and ventricular arrhythmias. It is becoming clearer that pathogenic variants in desmosomal genes such as PKP2 are not only responsible for a mechanical dysfunction of the intercalated disc (ID), but are also the cause of various pro-arrhythmic mechanisms. In this review, we discuss in detail the different molecular interactions associated with desmosomal pathogenic variants, and their contribution to various ACM phenotypes.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy, which is associated with life-threatening ventricular arrhythmias. Approximately 60% of patients carry a putative disease-causing genetic variant, but interpretation of genetic test results can be challenging. The aims of this study were to systematically reclassify genetic variants in patients with ARVC and to assess the impact on ARVC diagnosis. Methods: This study included patients from the Multicenter Zurich ARVC Registry who hosted a genetic variant deemed to be associated with the disease. Reclassification of pathogenicity was performed according to the modified 2015 American College of Medical Genetics criteria. ARVC diagnosis (categories: definite, borderline, possible) based on the 2010 Task Force Criteria was reclassified after genetic readjudication. Results: In 79 patients bearing 80 unique genetic variants, n=47 (58.8%) genetic variants were reclassified, and reclassification was judged to be clinically relevant in n=33 (41.3%). Variants in plakophilin-2 ( PKP2 ) were shown to reclassify less frequently as compared with other genes ( PKP2 , n=1, 8.3%; desmosomal non- PKP2 , n=20, 66.7%; nondesmosomal, n=26, 68.4%; P =0.001for overall comparison; PKP2 versus desmosomal non- PKP2, P =0.001; PKP2 versus nondesmosomal, P Conclusions: Given that approximately half of genetic variants were reclassified, with 10.1% of patients losing their definite disease status, accurate determination of variant pathogenicity is of utmost importance in the diagnosis of ARVC.

Background: 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. Objective: To assess the safety and efficacy of CA for atrial arrhythmias in patients with ARVC. Methods: 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. Results: Thirty-seven patients were enrolled in the study (age 50.2 ± 16.6 years, male 84%, CHA2DS2VASc 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 (n = 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. Conclusions: CA is safe and effective in managing atrial arrhythmias in patients with ARVC, with success rates comparable to the general population.

Funding Acknowledgements Type of funding sources: None. Background The 2010 Task Force Criteria (TFC), although representing the current gold standard to diagnose arrhythmogenic right ventricular cardiomyopathy (ARVC), have not been tested to differentiate ARVC from the athlete’s heart. Furthermore, not all 6 diagnostic categories are easy to obtain. Purpose We hypothesized that atrial dimensions are useful to differentiate between both entities. Therefore, we developed a new diagnostic score based upon readily available clinical parameters including atrial dimensions on TTE to help distinguishing the athlete’s heart from ARVC in daily clinical practice. Methods In this observational study, 37 patients with definite ARVC (from the Zurich ARVC Program) were compared to 68 athletes. Base on ROC analysis, the following echocardiographic, laboratory and electrocardiographic parameters were included in the final score: indexed right/left atrial volumes (RAVI/LAVI ratio), NT-proBNP, RVOT measurements (PLAX and PSAX adjusted for BSA) on TTE, tricuspid annular motion velocity (TAM) on TTE, precordial electrocardiographic T-wave inversions and depolarization abnormalities according to the TFC. Results ARVC patients had a higher RAVI/LAVI ratio (1.78 ± 1.6vs0.95 ± 0.3,p Conclusions ARVC patients present with significantly larger RA as 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. Abstract Figure. Novel clinical score

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.

Arrhythmogenic cardiomyopathy (ACM) is primarily a familial disease with autosomal dominant inheritance. Incomplete penetrance and variable expression are common, resulting in diverse clinical manifestations. Although recent studies on genotype&ndash, phenotype relationships have improved our understanding of the molecular mechanisms leading to the expression of the full-blown disease, the underlying genetic substrate and the clinical course of asymptomatic or oligo-symptomatic mutation carriers are still poorly understood. We aimed to analyze different phenotypic expression profiles of ACM in the context of the same familial genetic mutation by studying nine adult cases from four different families with four different familial variants (two plakophilin-2 and two desmoglein-2) from the Swiss Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Registry. The affected individuals with the same genetic variants presented with highly variable phenotypes ranging from no disease or a classical, right-sided disease, to ACM with biventricular presentation. Moreover, some patients developed early-onset, electrically unstable disease whereas others with the same genetic variants presented with late-onset electrically stable disease. Despite differences in age, gender, underlying genotype, and other clinical characteristics, physical exercise has been observed as the common denominator in provoking an arrhythmic phenotype in these families.

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease characterized by fibrofatty replacement of the myocardium and ventricular arrhythmias. Biventricular (BiV) involvement in ARVC may lead to heart failure. Purpose This study aimed to investigate the role of novel plasma biomarkers soluble (s)ST2, Galectin-3 (Gal-3) and GDF-15 in predicting BiV involvement and adverse outcomes in ARVC patients. Methods ARVC patients from two independent cohorts were studied. 108 patients were included from the discovery cohort and 47 patients were included from a second validation cohort. All patients had a definite ARVC diagnosis at time of blood withdrawal. sST2, Gal-3 and GDF-15 were independently correlated with NT-proBNP, left ventricular (LV) ejection fraction, late gadolinium enhancement by cardiac magnetic resonance (CMR) imaging and clinical outcome. Results ARVC patients with LV involvement had higher levels of sST2 and GDF-15 as compared to controls and patients with isolated right ventricular involvement. sST2 and GDF-15 significantly correlated to late gadolinium enhancement on CMR and also correlated to adverse heart failure outcomes. Gal-3 was elevated in ARVC patients with and without LV involvement as compared to controls. The combined use of the three biomarkers (NT-proBNP, sST2 and GDF-15) showed the best performance in predicting LV involvement in both the discovery and the validation cohort. Plasma drawn from coronary arteries and coronary sinus showed a transmyocardial elevation of sST2. Conclusion Our study shows that sST2 and GDF-15 may predict BiV involvement and the combined use of NT-proBNP, sST2 and GDF-15 shows the best prediction of LV involvement in ARVC. Transmyocardial elevation of sST2 suggests that this biomarker is produced by myocardial tissue in ARVC. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Fuwai ARVC Program was supported by CAMS Innovation Fund for Medical Sciences and the National Natural Science Foundation of China, Zurich ARVC Program was supported by grants from the Schwyzer Foundation and Baugarten Foundation

Introduction Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) is an inherited condition, which is associated with potentially life-threatening ventricular arrhythmias in the young. Approximately 60% of patients carry a possibly disease-causing genetic variant. Purpose The aim of this study was to investigate the impact of the 2015 American College of Medical Genetics (ACMG) Criteria on ARVC diagnosis based on the 2010 Modified Task Force Criteria (TFC). Methods The study included 79 patients from the Swiss ARVC Registry who harbored a genetic variant deemed to be associated with the disease at initial screening, and classified them as definite, borderline or possible ARVC. Every variant found was re-classified on Varsome Genetics, based on the 2015 ACMG Criteria. Clinical information was then assessed at last available follow-up of every patient and ARVC diagnosis was reclassified based on the newest genetic evidence available. Results In 42 out of 79 patients (53.2%), genetic variants were reclassified. Out of these, 33 variants (41.8%) were downgraded from pathogenic (P) / likely pathogenic (LP) to either variants of unknown significance (VUS) or benign (B) / likely benign (LB). Three patients (3.8%) were upgraded from VUS / LP to P. Out of the 12 variants initially classified as VUS, 9 (75%) were reclassified as B or LB. Overall, 13 patients (16.5%) were downgraded from their initial diagnosis (11 from definite to borderline and 2 from borderline to possible). Conclusion A significant proportion of patients with ARVC diagnosed based on the 2010 TFC were reclassified when the 2015 ACMG Criteria were taken into consideration. These findings may have clinical consequences, particularly for genetic cascade screening of family members of ARVC patients and necessitate reassessment of genetic variants of index patients who were previously diagnosed with ARVC. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): University Hospital Zurich

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 two 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 excellent prediction of biventricular involvement in ARVC.

The clinical presentation of cardiac sarcoidosis (CS) may resemble that of arrhythmogenic right ventricular cardiomyopathy (ARVC).The purpose of this study was to identify clinical variables to better discriminate between patients with genetically determined ARVC and those with CS fulfilling definite 2010 ARVC Task Force Criteria (TFC).In this multicenter study, 10 patients with CS fulfilling definite 2010 ARVC TFC were age and gender matched with 10 genetically proven ARVC patients. A cardiacThe 2010 ARVC TFC did not reliably differentiate between the 2 diseases. CS patients presented with longer PR intervals, advanced atrioventricular block (AVB), and longer QRS duration (P .001 and P = .009, respectively), whereas T-wave inversions (TWIs) in the peripheral leads were more common in ARVC patients (P = .009). CS patients presented with more extensive left ventricular involvement and lower left ventricular ejection fraction (LVEF), whereas ARVC patients had a larger right ventricular outflow tract (RVOT) (P = .044). PET scan positivity was only present in CS patients (90% vs 0%).The 2010 ARVC TFC do not reliably differentiate between CS patients fulfilling 2010 ARVC TFC and those with hereditary ARVC. Prolonged PR interval, advanced AVB, longer QRS duration, right ventricular apical involvement, reduced LVEF, and positive

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Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is frequently associated with mutations in genes coding for desmosomal proteins. In this study, we investigated the association of genetic status with ARVC progression as defined by echocardiographic parameters. Methods We tested 62 ARVC patients for their genetic profile. Accordingly, they were grouped in mutation positive (48 (77%) patients; median age 48.5 years; 33 (69%) males), and mutation negative (14 (23%) patients; median age 45 years; 10 (71%) males). Prevalent mutations were Desmoglein-2 (DSG2) in 16 (26%), Desmoplakin (DSP) in 14 (23%), and Plakophilin-2 (PKP2) in 9 (15%) patients. Results At baseline, there were no significant differences in clinical characteristics between the two groups. Patients were followed-up for a median time period of 1420 days, and there was no significant difference in the duration of follow-up between the two groups (p=0.05). In the mutation positive group, there was a significant increase in right ventricular end-diastolic area (p=0.002), right atrial short (p=0.008) and long (p=0.002) diameter, left atrial diameter (p=0.014), and a decrease in left ventricular ejection fraction (p=0.014) during follow up. Right ventricular functial parameters did not change significantly (tricuspid annular plane systolic excursion: p=0.24; fractional area change: p=0.088). In the mutation negative group, none of the aforementioned echocardiographic findings exhibited any significant difference during follow-up: right ventricular end-diastolic area (p=0.1); right atrial short (p=0.7) and long (p=0.9) diameter, left atrial diameter (p=0.6), and left ventricular ejection fraction (p=0.3). Similarly, right ventricular functional parameters did not change significantly (tricuspid annular plane systolic excursion: p=0.77; fractional area change: p=0.80. Results are summarized in the figure. Change in echocardiographic findings. Conclusions There is a strong association between echocardiographic progression of ARVC phenotype and the presence of a pathogenic mutation. Such mutations should be searched in all patients with an ARVC phenotype, and mutation positive individuals should be followed-up in shorter intervals.

Diese aktuelle Zusammenstellung supraventrikularer Tachykardien sowie der akuten Erfolgs- und Komplikationsraten von Ablationsbehandlungen eines universitaren Zentrums zeigt verschiedene interessante Ergebnisse.

Aims Short QT syndrome (SQTS) is a rare cardiac channelopathy characterized by a shortened corrected QT (QTc)-interval that can lead to ventricular arrhythmias and sudden cardiac death. The aim of this study was to investigate the clinical phenotypes and long-term outcomes of three families harbouring genetic mutations associated with the SQTS. Methods and results Clinical data included medical history, physical examination, 12-lead ECG, 24-h Holter-ECG, and transthoracic echocardiography from three index patients and their first-degree relatives. Next generation clinical exome sequencing and genetic cascade screening were performed in index patients and their relatives, respectively. Two index patients experienced malignant ventricular arrhythmias and one patient suffered from arrhythmogenic syncope during a median follow-up period of 8 years. They all had genetic mutations associated with the SQTS. Two mutations were found in the KCNH2 gene, and one in the CACNA2D gene. One patient had an additional SCN10A variant. Alive and mutation-positive family members had short QTc-intervals, but no further phenotypic manifestations. None of the mutation-negative family members had an abnormal ECG or any symptoms. In all patients with shortened QTc-intervals, the QTc-interval had a low long-term variability and QTc shortening always remained detectable by 12-lead ECG. Conclusion This study shows the variety of phenotypic manifestations in different families with SQTS. It further emphasizes the importance of a 12-lead ECG for early diagnosis, and the utility of next generation sequencing for the identification of mutations associated with the SQTS.

Aims Right ventricular outflow tract (RVOT) dilation is one of the echocardiographic criteria in the 2010 revised Task Force Criteria (TFC) of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D). However, studies comparing cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE) suggest a lower diagnostic accuracy of TTE due to its operator dependence and limited reproducibility. The goal of this study was to compare the 2010 TFC measures of RVOT dilation with three alternative measures for improving the echocardiographic assessment of RVOT in patients with ARVC/D. Methods and results In this multicentre study, CMR and TTE were performed in 38 patients with a definite, borderline, or possible ARVC/D diagnosis and in 10 healthy controls. Besides the echocardiographic RVOT measurements listed by the 2010 TFC, we assessed three additional end-diastolic RVOT diameters. These included the RVOT diameter defined by the parasternal long axis M-mode of the aortic sinus portion (RVOT3), that defined by the parasternal long axis M-mode of the left ventricle (RVOT4), and that obtained by the parasternal short axis view of the distal RVOT proximal to the pulmonary valve (RVOT5). RVOT4 provided the best correlation between CMR and TTE (r = 0.92, [95% confidence interval (CI): 0.84-0.96; P

Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by right ventricular myocardial replacement and life-threatening ventricular arrhythmias. Desmosomal gene mutations are sometimes identified, but clinical and genetic diagnosis remains challenging. Desmosomal skin disorders can be caused by desmosomal gene mutations or autoantibodies. We sought to determine if anti-desmosome antibodies are present in subjects with ARVC. Methods and results We evaluated ARVC subjects and controls for antibodies to cardiac desmosomal cadherin proteins. Desmoglein-2 (DSG2), desmocollin-2, and N-cadherin proteins on western blots were exposed to sera, in primary and validation cohorts of subjects and controls, as well as the naturally occurring Boxer dog model of ARVC. We identified anti-DSG2 antibodies in 12/12 and 25/25 definite ARVC cohorts and 7/8 borderline subjects. Antibody was absent in 11/12, faint in 1/12, and absent in 20/20 of two control cohorts. Anti-DSG2 antibodies were present in 10/10 Boxer dogs with ARVC, and absent in 18/18 without. In humans, the level of anti-DSG2 antibodies correlated with the burden of premature ventricular contractions (r = 0.70), and antibodies caused gap junction dysfunction, a common feature of ARVC, in vitro. Anti-DSG2 antibodies were present in ARVC subjects regardless of whether an underlying mutation was identified, or which mutation was present. A disease-specific DSG2 epitope was identified. Conclusion Anti-DSG2 antibodies are a sensitive and specific biomarker for ARVC. The development of autoimmunity as a result of target-related mutations is unique. Anti-DSG2 antibodies likely explain the cardiac inflammation that is frequently identified in ARVC and may represent a new therapeutic target.

The main aim of this paper is to characterize vortical flow structures in the healthy human right atrium, their impact on wall shear stresses and possible implications for atrial thrombus formation. 3D Particle Tracking Velocimetry is applied to a novel anatomically accurate compliant silicone right heart model to study the phase averaged and fluctuating flow velocity within the right atrium, inferior vena cava and superior vena cava under physiological conditions. We identify the development of two vortex rings in the bulk of the right atrium during the atrial filling phase leading to a rinsing effect at the atrial wall which break down during ventricular filling. We show that the vortex ring formation affects the hemodynamics of the atrial flow by a strong correlation (ρ = 0.7) between the vortical structures and local wall shear stresses. Low wall shear stress regions are associated with absence of the coherent vortical structures which might be potential risk regions for atrial thrombus formation. We discuss possible implications for atrial thrombus formation in different regions of the right atrium., Scientific Reports, 7, ISSN:2045-2322

Background. Falls and fractures in the elderly are among the leading causes of disability. We investigated whether pacemaker implantation prevents falls in patients with SND in a large cohort of patients. Methods. Patient demographics and medical history were collected prospectively. Fall history was retrospectively reconstituted from available medical records. The 10-year probability for major osteoporotic fractures was calculated retrospectively from available medical records using the Swiss fracture risk assessment tool FRAX-Switzerland. Results. During a mean observation period of 2.3 years after implantation, the rates of fallers and injured fallers with fracture were reduced to 15% and 6%, respectively. This corresponds to a relative reduction in the number of fallers of 75% (P < 0.001) and of injured fallers of 63% (P = 0.014) after pacemaker implantation. Similarly, the number of falls was reduced from 60 (48%) before pacemaker implantation to 22 (18%) thereafter (relative reduction 63%, P = 0.035) and the number of falls with injury from 22 (18%) to 7 (6%), which corresponds to a relative reduction of 67%, P = 0.013. Conclusion. In patients with SND, pacemaker implantation significantly reduces the number of patients experiencing falls, the total number of falls, and the risk for osteoporotic fractures.

Background: Awareness of risks associated with radiation exposure to patients and medical staff has significantly increased. It has been reported before that the use of advanced three-dimensional electroanatomical mapping (EAM) system significantly reduces fluoroscopy time, however this study aimed for zero or near zero fluoroscopy ablation to assess its feasibility and safety in ablation of atrial fibrillation (AF) and other tachyarrhythmias in a “real world” experience of a single tertiary care center. Methods: This was a single-center study where ablation procedures were attempted without fluoroscopy in 34 consecutive patients with different tachyarrhythmias under the support of EAM system. When transseptal puncture (TSP) was needed, it was attempted under the guidance of intracardiac echocardiography (ICE). Results: Among 34 patients consecutively enrolled in this study, 28 (82.4%) patients were referred for radiofrequency ablation (RFA) of AF, 3 (8.8%) patients for ablation of right ventricular outflow tract (RVOT) ventricular extrasystole (VES), 1 (2.9%) patient for ablation of atrioventricular nodal reentry tachycardia (AVNRT), 2 (5.9%) patients for typical atrial flutter ablation. In 21 (62%) patients the en- tire procedure was carried out without the use of fluoroscopy. Among 28 AF patients, 15 (54%) patients underwent ablation without the use of fluoroscopy and among these 15 patients, 10 (67%) patients required TSP under ICE guidance while 5 (33%) patients the catheters were introduced to left atrium through a patent foramen ovale. In 13 AF patients, fluoroscopy was only required for double TSP. The total procedure time of AF ablation was 130 ± 50 min. All patients referred for atrial flutter, AVNRT, and VES of the RVOT ablation did not require any fluoroscopy. Conclusions: This study demonstrates the feasibility of zero or near zero fluoroscopy procedure including TSP with the support of EAM and ICE guidance in a “real world” experience of a single tertiary care center. When fluoroscopy was required, it was limited to TSP hence keeping the radiation dose very low.

Aims Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is characterized by fibrofatty infiltration of the myocardium and ventricular arrhythmias that may lead to sudden cardiac death. It has been observed that male patients develop the disease earlier and present with more severe phenotypes as compared to females. Thus, we hypothesized that serum levels of sex hormones may contribute to major arrhythmic cardiovascular events (MACE) in patients with ARVC/D. Methods and results The serum levels of five sex hormones, sex hormone-binding globulin, high sensitivity troponin T, pro-brain natriuretic peptide, cholesterol, triglycerides, insulin, and glucose were measured in 54 ARVC/D patients (72% male). Twenty-six patients (48%) experienced MACE. Total and free testosterone levels were significantly increased in males with MACE as compared to males with a favourable outcome, whereas estradiol was significantly lower in females with MACE as compared to females with a favourable outcome. Increased testosterone levels remained independently associated with MACE in males after adjusting for age, body mass index, Task Force criteria, ventricular function, and desmosomal mutation status. Furthermore, an induced pluripotent stem cell-derived ARVC/D cardiomyocyte model was used to investigate the effects of sex hormones. In this model, testosterone worsened and estradiol improved ARVC/D-related pathologies such as cardiomyocyte apoptosis and lipogenesis, strongly supporting our clinical findings. Conclusions Elevated serum testosterone levels in males and decreased estradiol levels in females are independently associated with MACE in ARVC/D, and directly influence disease pathology. Therefore, determining the levels of sex hormones may be useful for risk stratification and may open a new window for preventive interventions.

Background— The value of standard 2-dimensional transthoracic echocardiographic parameters for risk stratification in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is controversial. Methods and Results— We investigated the impact of RV fractional area change (FAC) and tricuspid annulus plane systolic excursion (TAPSE) for the prediction of major adverse cardiovascular events (MACE) defined as the occurrence of cardiac death, heart transplantation, survived sudden cardiac death, ventricular fibrillation, sustained ventricular tachycardia, or arrhythmogenic syncope. Among 70 patients who fulfilled the 2010 ARVC/D Revised Task Force Criteria and underwent baseline transthoracic echocardiography, 37 (53%) patients experienced MACE during a median follow-up period of 5.3 (interquartile range, 1.8–9.8) years. Average values for FAC, TAPSE, and TAPSE indexed to body surface area (BSA) decreased over time ( P =0.03 for FAC, P =0.03 for TAPSE, and P =0.01 for TAPSE/BSA, each versus baseline). In contrast, median RV end-diastolic area increased ( P =0.001 versus baseline). Based on the results of Kaplan–Meier estimates, the time between baseline transthoracic echocardiography and experiencing MACE was significantly shorter for patients with FAC P P =0.02), or right atrial short axis/BSA ≥25 mm/m 2 ( P =0.04) at baseline. A reduced FAC constituted the strongest predictor of MACE (hazard ratio, 1.08 per 1% decrease; 95% confidence interval, 1.04–1.12; P Conclusions— This long-term observational study indicates that TAPSE and dilation of right-sided cardiac chambers are associated with an increased risk for MACE in patients with ARVC/D with advanced disease and a high risk for adverse events. However, FAC is the strongest echocardiographic predictor of adverse outcome in these patients. Our data advocate a role for transthoracic echocardiography in risk stratification in patients with ARVC/D, although our results may not be generalizable to lower-risk ARVC/D cohorts.

A 52-year-old male patient, a former competitive athlete, was admitted to the hospital because of recurrent episodes of palpitations and presyncope, which occurred while he was running in the course of the previous 12 months. Family history was significant for a first-degree cousin who received an implantable cardioverter-defibrillator (ICD) at 38 years of age because of an unclassified cardiomyopathy. An initial resting 12-lead ECG showed sinus rhythm at a heart rate of 57 beats per minute with an atypical right bundle-branch block, extensive notching of the QRS complex in leads V1 to V3, visible late potentials (resembling epsilon waves) in the inferolateral leads, T-wave inversions in leads V1 to V4, and one ventricular beat with left bundle branch block morphology and superior axis as well (Figure 1, top). Exercise testing induced a sustained ventricular tachycardia (VT) at a rate of 200 beats per minute with left bundle-branch block morphology. Ischemic heart disease was ruled out by coronary angiography. Transthoracic echocardiography (TTE), cardiac magnetic resonance (CMR), and right ventricular (RV) angiography demonstrated RV dilatation, a reduced RV function with wall thinning, and akinesis/dyskinesis of the RV apex, inferior wall, and the subtricuspid area (white arrows), and late gadolinium enhancement within the RV and left ventricular (LV) lateral wall, as well (Figure 2). Subsequently, an electrophysiological (EP) study including high-density electroanatomic voltage mapping was performed with the induction of a nonsustained VT with left bundle-branch block morphology and superior axis (Figure 1, bottom) at a rate of 230 beats per minute. Electroanatomic voltage mapping demonstrated low-voltage areas and scar within the RV corresponding to the regional wall motion abnormalities (Figure 3). Endomyocardial biopsies taken from the RV septum revealed some fibrotic infiltration surrounding the myocytes. Genetic testing yielded a severe heterozygous mutation of desmoplakin at position E1181, resulting in a …

The use of electroanatomical mapping can facilitate the identification of the ideal cryoablation site by providing a three-dimensional map of the earliest activation site. Combined use of the cryoablation technology with electroanatomical mapping can further increase the precision and safety of the procedure by applying test applications at a lower energy level.

We appreciated the interest of Barison and colleagues in our International Consensus Statement on the treatment of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D).1 Our document provided a comprehensive overview and recommendations for risk stratification and therapy of patients fulfilling the diagnostic criteria for ARVC/D. These criteria had been addressed by a previous International Task Force consensus document dedicated to diagnosis of ARVC/D.2 According to the revised criteria proposed by the International Task Force in 2010, the diagnosis of ARVC/D is based on the presence of major and minor criteria encompassing electrocardiographic, arrhythmic, morphological, histopathologic, and genetic factors. Diagnosis of definite ARVC/D is fulfilled in the presence of 2 major criteria or 1 major plus 2 minor or 4 minor criteria from different groups; the ARVC/D diagnosis is possible or borderline in the presence of insufficient criteria. In their Letter to the Editor, Barison and colleagues emphasized the valuable role of cardiac magnetic resonance (CMR) for diagnosis of ARVC/D, which relies on its ability to combine evaluation of ventricular size, function, and regional wall motion with characterization by late-gadolinium enhancement (LGE) of fibro-fatty myocardial scar, which is the hallmark lesion of ARVC/D. We totally agree that CMR is becoming the gold standard tool for detection of structural and functional ventricular abnormalities in ARVC/D. In the 2010 International Task Force consensus document, CMR was appropriately included among the diagnostic imaging techniques, and specific CMR reference values for normal (and abnormal) ventricular size, systolic function, and regional dyssynergy were provided. Tissue characterization by LGE was not included among these diagnostic criteria because of the potential risk of misdiagnosis of ARVC/D related to the difficulty of assessing LGE at the level of the thin right ventricular wall and possible confusion with normal epicardial fat tissue. More recently, the frequent involvement by the disease of the left ventricular wall in the form of epicardial-mediomural LGE has been recognized. As pointed out by the authors, LV LGE may enhance sensitivity for early/minor or predominant left variants of the ARVC/D; however, its diagnostic accuracy remains to be established. The prognostic role of CMR and, in particular, of postcontrast sequences for tissue characterization in patients with a diagnosis of definitive ARVC/D remains elusive. In our consensus statement on the treatment of ARVC/D, we performed a systematic review of outcome studies on ARVC/D available in the literature to identify predictor variables that were associated with an increased risk of major arrhythmic events (ie, sudden cardiac death, appropriate defibrillator interventions, or defibrillator therapy on fast ventricular tachycardia/ventricular fibrillation), nonsudden cardiac death, or heart transplantation in at least 1 published multivariable analysis. Although the predicting value of CMR for worse arrhythmic outcome was shown in the general population of patients showing premature ventricular beats with a left bundle branch morphology4 and in patients with suspected diagnosis of ARVC/D,5 no specific features of CMR, either alone or in combination, have been reported yet as independent predictors of life-threatening arrhythmic events in patients with a definite diagnosis of ARVC/D. This lack of evidence underscores the importance of undertaking future studies on this field.

Background Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is mainly an autosomal dominant disease characterized by fibrofatty infiltration of the right ventricle, leading to ventricular arrhythmias. Mutations in desmosomal proteins can be identified in about half of the patients. The pathogenic mechanisms leading to disease expression remain unclear. Objective The purpose of this study was to investigate myocardial expression profiles of candidate molecules involved in the pathogenesis of ARVC/D. Methods Myocardial messenger RNA (mRNA) expression of 62 junctional molecules, 5 cardiac ion channel molecules, 8 structural molecules, 4 apoptotic molecules, and 6 adipogenic molecules was studied. The averaged expression of candidate mRNAs was compared between ARVC/D samples (n = 10), nonfamilial dilated cardiomyopathy (DCM) samples (n = 10), and healthy control samples (n = 8). Immunohistochemistry and quantitative protein expression analysis were performed. Genetic analysis using next generation sequencing was performed in all patients with ARVC/D. Results Following mRNA levels were significantly increased in patients with ARVC/D compared to those with DCM and healthy controls: phospholamban (P ≤ .001 vs DCM; P ≤ .001 vs controls), healthy tumor protein 53 apoptosis effector (P = .001 vs DCM; P ≤ .001 vs controls), and carnitine palmitoyltransferase 1β (P ≤ .001 vs DCM; P = 0.008 vs controls). Plakophillin-2 (PKP-2) mRNA was downregulated in patients with ARVC/D with PKP-2 mutations compared with patients with ARVC/D without PKP-2 mutations (P = .04). Immunohistochemistry revealed significantly increased protein expression of phospholamban, tumor protein 53 apoptosis effector, and carnitine palmitoyltransferase 1β in patients with ARVC/D and decreased PKP-2 expression in patients with ARVC/D carrying a PKP-2 mutation. Conclusion Changes in the expression profiles of sarcolemmal calcium channel regulation, apoptosis, and adipogenesis suggest that these molecular pathways may play a critical role in the pathogenesis of ARVC/D, independent of the underlying genetic mutations.