Genetic characterization of KCNQ1 variants improves risk stratification in type 1 long QT syndrome patients.

AIMS: KCNQ1 mutations cause QTc prolongation increasing life-threatening arrhythmias risks. Heterozygous mutations [type 1 long QT syndrome (LQT1)] are common. Homozygous KCNQ1 mutations cause type 1 Jervell and Lange-Nielsen syndrome (JLNS) with deafness and higher sudden cardiac death risk. KCNQ1 variants causing JLNS or LQT1 might have distinct phenotypic expressions in heterozygous patients. The aim of this study is to evaluate QTc duration and incidence of long QT syndrome-related cardiac events according to genetic presentation. METHODS AND RESULTS: We enrolled LQT1 or JLNS patients with class IV/V KCNQ1 variants from our inherited arrhythmia clinic (September 1993 to January 2023). Medical history, ECG, and follow-up were collected. Additionally, we conducted a thorough literature review for JLNS variants. Survival curves were compared between groups, and multivariate Cox regression models identified genetic and clinical risk factors. Among the 789 KCNQ1 variant carriers, 3 groups were identified: 30 JLNS, 161 heterozygous carriers of JLNS variants (HTZ-JLNS), and 550 LQT1 heterozygous carriers of non-JLNS variants (HTZ-Non-JLNS). At diagnosis, mean age was 3.4 ± 4.7 years for JLNS, 26.7 ± 21 years for HTZ-JLNS, and 26 ± 21 years for HTZ-non-JLNS; 55.3% were female; and the mean QTc was 551 ± 54 ms for JLNS, 441 ± 32 ms for HTZ-JLNS, and 467 ± 36 ms for HTZ-Non-JLNS. Patients with heterozygous JLNS mutations (HTZ-JLNS) represented 22% of heterozygous KCNQ1 variant carriers and had a lower risk of cardiac events than heterozygous non-JLNS variant carriers (HTZ-Non-JLNS) [hazard ratio (HR) = 0.34 (0.22-0.54); P < 0.01]. After multivariate analysis, four genetic parameters were independently associated with events: haploinsufficiency [HR = 0.60 (0.37-0.97); P = 0.04], pore localization [HR = 1.61 (1.14-1.2.26); P < 0.01], C-terminal localization [HR = 0.67 (0.46-0.98); P = 0.04], and group [HR = 0.43 (0.27-0.69); P < 0.01]. CONCLUSION: Heterozygous carriers of JLNS variants have a lower risk of cardiac arrhythmic events than other LQT1 patients.

Clinical presentation of calmodulin mutations: the International Calmodulinopathy Registry.

AIMS: Calmodulinopathy due to mutations in any of the three CALM genes (CALM1-3) causes life-threatening arrhythmia syndromes, especially in young individuals. The International Calmodulinopathy Registry (ICalmR) aims to define and link the increasing complexity of the clinical presentation to the underlying molecular mechanisms. METHODS AND RESULTS: The ICalmR is an international, collaborative, observational study, assembling and analysing clinical and genetic data on CALM-positive patients. The ICalmR has enrolled 140 subjects (median age 10.8 years [interquartile range 5-19]), 97 index cases and 43 family members. CALM-LQTS and CALM-CPVT are the prevalent phenotypes. Primary neurological manifestations, unrelated to post-anoxic sequelae, manifested in 20 patients. Calmodulinopathy remains associated with a high arrhythmic event rate (symptomatic patients, n = 103, 74%). However, compared with the original 2019 cohort, there was a reduced frequency and severity of all cardiac events (61% vs. 85%; P = .001) and sudden death (9% vs. 27%; P = .008). Data on therapy do not allow definitive recommendations. Cardiac structural abnormalities, either cardiomyopathy or congenital heart defects, are present in 30% of patients, mainly CALM-LQTS, and lethal cases of heart failure have occurred. The number of familial cases and of families with strikingly different phenotypes is increasing. CONCLUSION: Calmodulinopathy has pleiotropic presentations, from channelopathy to syndromic forms. Clinical severity ranges from the early onset of life-threatening arrhythmias to the absence of symptoms, and the percentage of milder and familial forms is increasing. There are no hard data to guide therapy, and current management includes pharmacological and surgical antiadrenergic interventions with sodium channel blockers often accompanied by an implantable cardioverter-defibrillator.

Feasibility of adenosine stress cardiovascular magnetic resonance perfusion imaging in patients with MR-conditional transvenous permanent pacemakers and defibrillators.

BACKGROUND: The use of stress perfusion-cardiovascular magnetic resonance (CMR) imaging remains limited in patients with implantable devices. The primary goal of the study was to assess the safety, image quality, and the diagnostic value of stress perfusion-CMR in patients with MR-conditional transvenous permanent pacemakers (PPM) or implantable cardioverter-defibrillators (ICD). METHODS: Consecutive patients with a transvenous PPM or ICD referred for adenosine stress-CMR were enrolled in this single-center longitudinal study. The CMR protocol was performed using a 1.5 T system according to current guidelines while all devices were put in MR-mode. Quality of cine, late-gadolinium-enhancement (LGE), and stress perfusion sequences were assessed. An ischemia burden of ≥ 1.5 segments was considered significant. We assessed the safety, image quality and the occurrence of interference of the magnetic field with the implantable device. In case of ischemia, we also assessed the correlation with the presence of significant coronary lesions on coronary angiography. RESULTS: Among 3743 perfusion-CMR examinations, 66 patients had implantable devices (1.7%). Image quality proved diagnostic in 98% of cases. No device damage or malfunction was reported immediately and at 1 year. Fifty patients were continuously paced during CMR. Heart rate and systolic blood pressure remained unchanged during adenosine stress, while diastolic blood pressure decreased (p = 0.007). Six patients (9%) had an ischemia-positive stress CMR and significant coronary stenoses were confirmed by coronary angiography in all cases. CONCLUSION: Stress perfusion-CMR is safe, allows reliable ischemia detection, and provides good diagnostic value.

[Epicardial adipose tissue and atrial fibrillation]. / Tissu adipeux épicardique et fibrillation auriculaire.

Atrial fibrillation (AF) is the most common arrhythmia encountered in adults; it is associated with a significant morbidity and mortality. Obesity is a risk factor contributing to AF occurrence. Recently, interest has focused on epicardial adipose tissue (EAT), defined as a fatty deposit located between the epicardium and the visceral pericardium. Its characteristics are distinct from classic adipose deposits: it infiltrates the epicardial myocardium and secretes cytokines, which modulate cardiomyocyte electrophysiology and cardiac remodeling. Different studies show that EAT can be an independent risk factor for AF and that EAT thickness, as measured by CT or MRI, could predict the presence, severity and recurrence of AF.

La fibrillation auriculaire (FA) est l'arythmie la plus fréquemment rencontrée chez l'adulte ; elle est associée à une morbi-mortalité importante. L'obésité est un facteur de risque contribuant à sa survenue. Récemment, l'intérêt s'est porté sur le tissu adipeux épicardique (TAE), défini comme un dépôt adipeux situé entre l'épicarde et le péricarde viscéral. Ses caractéristiques sont distinctes des dépôts adipeux classiques : il infiltre le myocarde épicardique et sécrète des cytokines modulant l'électrophysiologie des cardiomyocytes et provoquant un remodelage fibro-adipeux cardiaque. Différentes études montrent que le TAE peut être un facteur de risque indépendant de survenue de FA. L'épaisseur du TAE mesurée par CT-scan ou par IRM pourrait être utilisée comme facteur prédictif de la présence, de la gravité et de la récidive de FA.

Myocardial extracellular volume by T1 mapping: a new marker of arrhythmia in mitral valve prolapse.

OBJECTIVES: We aimed to evaluate the relationship between mitral annular disjunction (MAD) severity and myocardial interstitial fibrosis at the left ventricular (LV) base in patients with mitral valve prolapse (MVP), and to assess the association between severity of interstitial fibrosis and the occurrence of ventricular arrhythmic events. BACKGROUND: In MVP, MAD has been associated with myocardial replacement fibrosis and arrhythmia, but the importance of interstitial fibrosis remains unknown. METHODS: In this retrospective study, 30 patients with MVP and MAD (MVP-MAD) underwent cardiovascular magnetic resonance (CMR) with assessment of MAD length, late gadolinium enhancement (LGE), and basal segments myocardial extracellular volume (ECVsyn). The control group included 14 patients with mitral regurgitation (MR) but no MAD (MR-NoMAD) and 10 patients with normal CMR (NoMR-NoMAD). Fifteen MVP-MAD patients underwent 24 h-Holter monitoring. RESULTS: LGE was observed in 47% of MVP-MAD patients and was absent in all controls. ECVsyn was higher in MVP-MAD (30 ± 3% vs 24 ± 3% MR-NoMAD, p < 0.001 and vs 24 ± 2% NoMR-NoMAD, p < 0.001), even in MVP-MAD patients without LGE (29 ± 3% vs 24 ± 3%, p < 0.001 and vs 24 ± 2%, p < 0.001, respectively). MAD length correlated with ECVsyn (rho = 0.61, p < 0.001), but not with LGE extent. Four patients had history of out-of-hospital cardiac arrest; LGE and ECVsyn were equally performant to identify those high-risk patients, area under the receiver operating characteristic (ROC) curve 0.81 vs 0.83, p = 0.84). Among patients with Holter, 87% had complex ventricular arrhythmia. ECVsyn was above the cut-off value in all while only 53% had LGE. CONCLUSION: Increase in ECVsyn, a marker of interstitial fibrosis, occurs in MVP-MAD even in the absence of LGE, and was correlated with MAD length and increased risk of out-of-hospital cardiac arrest. ECV should be includedin the CMR examination of MVP patients in an effort to better assess fibrous remodelling as it may provide additional value beyond the assessment of LGE in the arrhythmic risk stratification.

[Sinus node dysfunction, Brugada syndrome and long QT syndrome affecting the same patient†: when genetics can't make head or tail of it]. / Dysfonction sinusale, syndrome de Brugada et syndrome du QT long chez un même patient - Quand la génétique y perd son latin.

The gene SCN5A encodes the cardiac sodium channel which, through the conduction of Na+ current into the cell, generates the fast upstroke of the action potential of cardiomyocytes. Pathogenic variants of SCN5A have been causally associated to several hereditary cardiac diseases including, among others, Brugada syndrome, congenital long QT syndrome and sinus node dysfunction. Recently, overlap syndromes have been described that are characterized by the simultaneous expression of mixed clinical phenotypes among two or more hereditary cardiac diseases associated to the gene SCN5A (HCD-SCN5A). For this reason, it is time to rethink about HCD-SCN5A as different expressions of the same complex spectrum encompassing multiple clinical phenotypes with pronounced overlaps instead of as distinct clinical entities.

Le gène SCN5A code pour le canal sodique cardiaque qui est responsable de la pente de dépolarisation rapide du potentiel d'action. Plusieurs cardiopathies héréditaires (CH) ont été associées à des variants pathogènes du gène SCN5A incluant, entre autres, le syndrome de Brugada, le syndrome du QT long congénital et la dysfonction sinusale. Récemment, des syndromes de chevauchement ont été également décrits, s'exprimant, chez un même patient, par un phénotype clinique mixte comprenant une combinaison des manifestations rapportées ci-dessus. Dans ce contexte, nous devrions donc reconsidérer cliniquement les CH impliquant le gène SCN5A comme des expressions différentes d'un même éventail de phénotypes cliniques avec chevauchements marqués plutôt que comme des entités cliniques distinctes et isolées.

Imaging of Carotid Plaque Neovascularization by Contrast-Enhanced Ultrasound and Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

BACKGROUND: Carotid plaque neovascularization (vasa vasorum [VV]) may be useful for detecting high-risk atherosclerotic plaques. Contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are 2 commonly used techniques for imaging VV of the carotid plaque, yet the relationship between their measurements remains unknown. OBJECTIVES: We aimed to blindly evaluate the correlation between CEUS and DCE-MRI in measuring carotid plaque VV. METHODS: We recruited subjects with asymptomatic carotid stenosis (≥50%). VV was graded by CEUS, based on richness of contrast signal, according to 3 different methods named CEUS_A, CEUS_B and CEUS_C on different point scales (the higher the values, the higher the estimated VV). A 3.0 T MRI scanner was used for VV quantification by DCE-MRI using gadolinium contrast kinetic modelling for computing the fractional plasma volume (vp) and transfer constant (Ktrans). RESULTS: The analysis included 30 patients. A significant correlation between CEUS and DCE-MRI findings was observed when CEUS_C was used for neovessel grading and DCE-MRI was used to determine adventitial (r = 0.460, p = 0.010) and plaque (r = 0.374, p = 0.042) Ktrans values. CEUS_B (r = 0.416, p = 0.022) and CEUS_C (r = 0.443, p = 0.014) grading showed a significant correlation with regard to the maximal Ktrans. CONCLUSIONS: We found a positive but weak correlation and a moderate diagnostic agreement between neovessels as visually graded by CEUS and adventitial neovessels assessed by DCE-MRI Ktrans in carotid atherosclerosis. These findings may help in understanding how VV density, flow, and permeability influence in vivo measurements by CEUS and DCE-MRI as well as in selecting the most appropriate variables and imaging method in future research and potentially in clinical settings. Further confirmative studies are necessary to confirm our results.

Long-term Outcomes of a Telementoring Program for Distant Teaching of Endovascular Aneurysm Repair.

PURPOSE: To prospectively evaluate the long-term outcomes after a telementoring program for distant teaching of endovascular aneurysm repair (EVAR) and the degree of EVAR procedure assimilation into routine practice. METHODS: A telementoring protocol using stepwise introduction of EVAR was implemented between a university care center and a remote vascular health care site; from March 1999 to October 2003, 49 EVAR patients (mean age 72 years; 48 men) were treated during telementoring at the remote center. After the telementoring period, 86 patients (mean age 71 years; 77 men) underwent EVAR procedures carried out at the secondary care center from November 2003 to July 2011. The long-term outcomes were compared between the EVAR procedures performed during telementoring with the procedures performed independently thereafter. RESULTS: No significant difference was appreciated between telementored and not telementored procedures either in 30-day mortality (4.1% vs 2.3%, p=0.621) or in the initial technical success (93.9% vs 97.7%, p=0.353). The telementored group showed no significant difference in overall aneurysm-related mortality (6.1% vs 2.3%, p=0.353) or in the overall complication rates (p=0.985). The reintervention rate was significantly lower among the unmentored procedures (11.6% vs 32.7%, p=0.004). In particular, significantly fewer patients underwent late endovascular procedures (1.2% vs 12.2%, p=0.009) and late percutaneous interventions (7.0% vs 20.4%, p=0.027) after telementoring ceased. CONCLUSION: The telementoring program followed here allowed excellent EVAR skill assimilation into the routine practice of a remote health care site. Telementoring is a feasible strategy to support skill introduction in remote medical facilities.

A combined "in vivo" noninvasive evaluation of carotid plaques using ultrasonography and high-resolution magnetic resonance - new insight into plaque burden and vulnerability.

BACKGROUND: Qualitative change in carotid plaques was prospectively evaluated by Gray Scale Median (GSM) analysis at repeated examinations "in vivo", in relation to quantitative change in carotid arterial geometry, as assessed by high-resolution magnetic resonance imaging (HR-MRI). PATIENTS AND METHODS: Duplex ultrasound with GSM analysis and HR-MRI at the carotid level were performed at baseline and 1- and 2-year follow up in 30 patients with < 70% carotid stenosis. Changes in GSM values (ΔGSM) were evaluated as the intra-individual difference between 2-year and baseline values. HR-MRI studies were evaluated for lumen area (LA), total vessel area (TVA), vessel wall area (VWA = TVA-LA) and normalized wall index (NWI = VWA/TVA). RESULTS: ΔGSM value distribution was divided into quartiles. Predominantly echolucent plaques with ΔGSM value in the lowest quartile (ΔGSM ≤- 8) showed a significantly greater mean 2-year LA (28.62 ± 10.9 mm2 vs. 17.88 ± 4.8 mm2, p = 0.04) and a greater mean 2-year TVA (83.64 ± 19.4 mm2 vs. 63.26 ± 9.2 mm2, p = 0.02) than predominantly echogenic plaques with ΔGSM value in the highest quartile (ΔGSM ≥8). CONCLUSIONS: Increasing echolucency during the 2-year follow up was associated with a 2-year lower degree of stenosis and higher tendency toward lumen preservation. By corroborating that plaque vulnerability is highly independent of stenosis severity, our study provided a possible new combined "in vivo" noninvasive approach for the assessment of carotid plaque vulnerability.

[Cardiac sarcoidosis: seven keypoints to remind in order to avoid misdiagnosis]. / Sarcoïdose cardiaque: sept points à rappeler pour ne pas manquer le diagnostic.

Early diagnosis of cardiac sarcoidosis remains difficult in the absence of specific symptoms. The evolution and prognosis of the disease are strongly correlated to an early and appropriate treatment. The multi-modality assessment based on cardiac MRI and positron emission tomography associated with computed tomography (PET/CT) has significantly improved the detection of cardiac sarcoidosis over the last two decades. These approaches appear as useful and suitable imaging strategy for the early diagnosis, the assessment of the disease extent as well as the management and therapeutic follow-up. This article is a didactic review on cardiac sarcoidosis, with a special focus on recent diagnostic and therapeutic modalities, prognosis and interest of imaging techniques.

Reduction of ST-elevation myocardial infarction in Canton Ticino (Switzerland) after smoking bans in enclosed public places--No Smoke Pub Study.

BACKGROUND: Second-hand smoke increases the risk of acute myocardial infarction. Canton Ticino (CT) first introduced a smoking ban in public places in 2007. This offered the opportunity to assess the long-term impact of a smoking ban on the incidence of ST-elevation myocardial infarctions (STEMI) compared with a population where the law was not yet implemented. METHODS: We assessed the incidence of STEMI hospitalizations per 100 000 inhabitants both during 3 years before and after the ban application in CT and in Canton Basel City (CBC), where this law was not yet applied. Data were obtained from the codified hospital registry (ICD-10 codes). RESULTS: In CT, the mean incidence of STEMI admissions during the 3 pre-ban years (123.7) was significantly higher than the incidence of admissions in each of the 3 post-ban years (92.9, 101.6 and 89.6 respectively; P <.024). Analysing population subsets, a post-ban reduction was observed among ≥65-year-old people of both sexes in each of the 3 post-ban years and in the <65-year age group during the first post-ban year (P = 0.02). Conversely, the mean incidence of STEMI hospitalizations in CBC (92.4) didn't change significantly in each of the 3 post-ban years (83.9, 83.3 and 79.5, P = NS) during the same period. However, a significant long-term reduction in STEMI admissions was observed in CBC among the male group with ≥65 years (P < 0.01). CONCLUSION: Our work suggests a significant impact of the smoke-free policy on the number of annual STEMI. Specific population subsets (i.e. ≥65-year-old females) were particularly affected by the smoking ban, showing a significant reduction in STEMI hospitalizations.

Cardiovascular evaluation of middle-aged individuals engaged in high-intensity sport activities: implications for workload, yield and economic costs.

BACKGROUND: The European Association of Cardiovascular Prevention and Rehabilitation (EACPR) recommends cardiovascular evaluation of middle-aged individuals engaged in sport activities. However, very few data exist concerning the impact of such position stand. We assessed the implications on workload, yield and economic costs of this preventive strategy. METHODS: Individuals aged 35-65 years engaged in high-intensity sports were examined following the EACPR protocol. Athletes with abnormal findings or considered at high-cardiovascular risk underwent additional examinations. The costs of the overall evaluation until diagnosis were calculated according to Swiss medical rates. RESULTS: 785 athletes (73% males, 46.8±7.3 years) were enrolled over a 13-month period. Among them, 14.3% required additional examinations: 5.1% because of abnormal ECG, 4.7% due to physical examination, 4.1% because of high-cardiovascular risk and 1.6% due to medical history. A new cardiovascular abnormality was established in 2.8% of athletes, severe hypercholesterolaemia in 1% and type 2 diabetes in 0.1%. Three (0.4%) athletes were considered ineligible for high-intensity sports, all of them discovered through an abnormal ECG. No athlete was diagnosed with significant coronary artery disease on the basis of a high-risk profile or an exercise ECG. The cost was US$199 per athlete and US$5052 per new finding. CONCLUSIONS: Cardiovascular evaluation of middle-aged athletes detected a new cardiovascular abnormality in about 3% of participants and a high-cardiovascular risk profile in about 4%. Some of these warranted exclusion of the athlete from high-intensity sport. The overall evaluation seems to be feasible at reasonable costs.

Fabry disease: development and progression of left ventricular hypertrophy despite long-term enzyme replacement therapy.

BACKGROUND: Enzyme replacement therapy (ERT) may halt or attenuate disease progression in patients with Anderson-Fabry disease (AFD). However, whether left ventricular hypertrophy (LVH) can be prevented by early therapy or may still progress despite ERT over a long-term follow-up is still unclear. METHODS: Consecutive patients with AFD from the Independent Swiss-Fabry Cohort receiving ERT who were at least followed up for 5 years were included. Cardiac progression was defined as an increase of >10 g/m2 in left ventricular mass index (LVMI) between the first and the last available follow-up transthoracic echocardiography. RESULTS: 60 patients (35 (23-48) years, 39 (65%) men) were followed up for 10.5 (7.2-12.2) years. 22 had LVH at ERT start (LVMI of 150±38 g/m2). During follow-up, 22 (36%, 34±15 years) had LVMI progression of 12.1 (7-17.6) g/m2 per 100 patient-years, of these 7 (11%, 29±13 years) with no LVH at baseline. Three of them progressed to LVH. LVMI progression occurred mostly in men (17 of 39 (43%) vs 5 of 21 (24%), p<0.01) and after the age of 30 years (17 of 22 (77%)). LVH at ERT start was associated with LVMI progression (OR 1.3, 95% CI 1.1 to 2.6; p=0.02). A total of 19 (31%) patients experienced a major AFD-related event. They were predominantly men (17 of 19, 89%), older (45±11 vs 32±9 years) with baseline LVH (12 of 19, 63%), and 10 of 19 (52%) presented with LVMI progression. CONCLUSIONS: Over a median follow-up of >10 years under ERT, 36% of the patients still had LVMI cardiac progression, and 32%, predominantly older men, experienced major AFD-related events. LVH at treatment initiation was a strong predictor of LVMI progression and adverse events on ERT.

The influence of cardiac arrhythmias on the detection of heartbeats in the photoplethysmogram: benchmarking open-source algorithms.

Objective.Cardiac arrhythmias are a leading cause of mortality worldwide. Wearable devices based on photoplethysmography give the opportunity to screen large populations, hence allowing for an earlier detection of pathological rhythms that might reduce the risks of complications and medical costs. While most of beat detection algorithms have been evaluated on normal sinus rhythm or atrial fibrillation recordings, the performance of these algorithms in patients with other cardiac arrhythmias, such as ventricular tachycardia or bigeminy, remain unknown to date.Approach. ThePPG-beatsopen-source framework, developed by Charlton and colleagues, evaluates the performance of the beat detectors namedQPPG,MSPTDandABDamong others. We applied thePPG-beatsframework on two newly acquired datasets, one containing seven different types of cardiac arrhythmia in hospital settings, and another dataset including two cardiac arrhythmias in ambulatory settings.Main Results. In a clinical setting, theQPPGbeat detector performed best on atrial fibrillation (with a medianF1score of 94.4%), atrial flutter (95.2%), atrial tachycardia (87.0%), sinus rhythm (97.7%), ventricular tachycardia (83.9%) and was ranked 2nd for bigeminy (75.7%) behindABDdetector (76.1%). In an ambulatory setting, theMSPTDbeat detector performed best on normal sinus rhythm (94.6%), and theQPPGdetector on atrial fibrillation (91.6%) and bigeminy (80.0%).Significance. Overall, the PPG beat detectorsQPPG,MSPTDandABDconsistently achieved higher performances than other detectors. However, the detection of beats from wrist-PPG signals is compromised in presence of bigeminy or ventricular tachycardia.

Endovascular abdominal aneurysm repair and impact of systematic preoperative embolization of collateral arteries: endoleak analysis and long-term follow-up.

PURPOSE: To report our results of endovascular aneurysm repair (EVAR) over a 10-year period using systematic preoperative collateral artery embolization. METHODS: From 1999 until 2009, 124 patients (117 men; mean age 70.8 years) with abdominal aortic aneurysm (AAA) underwent embolization of patent lumbar and/or inferior mesenteric arteries prior to elective EVAR procedures. Embolization was systematically attempted and, whenever possible, performed using microcoils and a coaxial technique. Follow-up included computed tomography and/or magnetic resonance imaging and abdominal radiography. RESULTS: The technical success for EVAR was 96% (119/124), with 4 patients dying within 30 days (3.2% perioperative mortality) and 1 type III endoleak accounting for the failures. Collateral arteries were occluded spontaneously or by embolization in 60 (48%) of 124 patients. The endoleak rate was 50.9% (74 in 61 patients), most of which were type II (19%). Over a mean clinical follow-up of 60.5±34.1 months (range 1-144), aneurysm sac dimensions decreased in 66 patients, increased in 19 patients, and were stable in 35. The endoleak rate was significantly higher in the patients with increasing sac diameter (p<0.001). Among the patients with patent collateral arteries, 38/64 (59.3%) developed 46 leaks, while 28 leaks appeared in 23 (41%) of 56 patients with collateral artery occlusion (p=0.069). The type II endoleak rate significantly differed between these two groups (47.8% vs. 3.6%, p<0.001). CONCLUSION: Preoperative collateral embolization seems to be a valid method of reducing the incidence of type II endoleak, improving the long-term outcome.

Conduction System Pacing versus Conventional Biventricular Pacing for Cardiac Resynchronization Therapy: Where Are We Heading?

Over the last few years, pacing of the conduction system (CSP) has emerged as the new standard pacing modality for bradycardia indications, allowing a more physiological ventricular activation compared to conventional right ventricular pacing. CSP has also emerged as an alternative modality to conventional biventricular pacing for the delivery of cardiac resynchronization therapy (CRT) in heart failure patients. However, if the initial clinical data seem to support this new physiological-based approach to CRT, the lack of large randomized studies confirming these preliminary results prevents CSP from being used routinely in clinical practice. Furthermore, concerns are still present regarding the long-term performance of pacing leads when employed for CSP, as well as their extractability. In this review article, we provide the state-of-the-art of CSP as an alternative to biventricular pacing for CRT delivery in heart failure patients. In particular, we describe the physiological concepts supporting this approach and we discuss the future perspectives of CSP in this context according to the implant techniques (His bundle pacing and left bundle branch area pacing) and the clinical data published so far.

Case report: First-in-human combined low-dose whole-heart irradiation and high-dose stereotactic arrhythmia radioablation for immunosuppressive refractory cardiac sarcoidosis and ventricular tachycardia.

Background: Cardiac sarcoidosis is associated with heart failure, conduction abnormalities, and life-threatening arrhythmias including ventricular tachycardia (VT). Radiotherapy has been suggested as a treatment for extra-cardiac sarcoidosis in patients refractory to immunomodulatory treatment. Methods: The effectiveness and safety of low-dose whole-heart radiotherapy for therapy refractory cardiac sarcoidosis were evaluated in a pre- and post-intervention case report comparing the 54 months before and after treatment. Immunomodulatory low-dose whole-heart irradiation as sarcoidosis treatment consisted of a 2 × 2 Gy scheme. Additionally, high-dose single-fraction stereotactic arrhythmia radioablation of 1 × 20 Gy was applied to the pro-arrhythmic region to manage the ventricular tachycardia episodes. Cardiac sarcoidosis disease activity was measured by hypermetabolic areas on repeated fluorodeoxyglucose ([18F]FDG)-PET/computed tomography (CT) scans and by evaluating changes in ventricular tachycardia episodes before and after treatment. Results: One patient with therapy refractory progressive cardiac sarcoidosis and recurrent ventricular tachycardia was treated. The cardiac sarcoidosis disease activity showed a durable regression of inflammatory disease activity from 3 months onwards. The [18F]FDG-PET/CT scan at 54 months did not show any signs of active cardiac sarcoidosis, and a state of remission was achieved. The number of sustained VT episodes was reduced by 95%. We observed that the development of moderate aortic valve regurgitation was likely irradiation-related. No other irradiation-related adverse events occurred, and the left ventricular ejection fraction remained stable. Conclusion: We report here for the first time on the beneficial and lasting effects of combined immunomodulatory low-dose whole-heart radiotherapy and high-dose stereotactic arrhythmia radioablation in a patient with therapy refractory cardiac sarcoidosis and recurrent VT.

SCN5A overlap syndromes: An open-minded approach.

SCN5A overlap syndromes are clinical entities that express a phenotype combining aspects of different canonical SCN5A-related arrhythmia syndromes or a variable arrhythmic phenotype among individuals carrying the same SCN5A mutation. Here we review the literature addressing SCN5A overlap syndromes as well as the principal mechanisms currently proposed. Among others, a multifactorial determination encompassing an interaction between SCN5A variant(s), other genetic polymorphisms, and possibly environmental factors seems the most plausible hypothesis.

New Insights in Central Venous Disorders. The Role of Transvenous Lead Extractions.

Over the last decades, the implementation of new technology in cardiac pacemakers and defibrillators as well as the increasing life expectancy have been associated with a higher incidence of transvenous lead complications over time. Variable degrees of venous stenosis at the level of the subclavian vein, the innominate trunk and the superior vena cava are reported in up to 50% of implanted patients. Importantly, the number of implanted leads seems to be the main risk factor for such complications. Extraction of abandoned or dysfunctional leads is a potential solution to overcome venous stenosis in case of device upgrades requiring additional leads, but also, in addition to venous angioplasty and stenting, to reduce symptoms related to the venous stenosis itself, i.e., the superior vena cava syndrome. This review explores the role of transvenous lead extraction procedures as therapeutical option in case of central venous disorders related to transvenous cardiac leads. We also describe the different extraction techniques available and other clinical indications for lead extractions such as lead infections. Finally, we discuss the alternative therapeutic options for cardiac stimulation or defibrillation in case of chronic venous occlusions that preclude the implant of conventional transvenous cardiac devices.