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STUDY OBJECTIVES: This study sought to examine the relationship between internet use, sleep, and internalizing disorder symptoms in adolescents with an evening circadian preference. METHODS: One hundred seventy-two adolescents aged 10–18 years with an evening circadian preference completed a week of sleep diaries and questionnaires about internet use and internalizing disorder symptoms. RESULTS: Adolescents reported internet use for 3.81 hours on weekdays and 5.44 hours on weekends, with > 90% having access to both a computer with internet and a personal cell phone. A majority of adolescents used the internet from 4–8 pm (71%) and from 9–11 pm (62%). Common online activities included listening to music (77%), watching videos (64%), communicating with others (64%), and doing homework (58%). Late-night internet use (9–11 pm) was associated with more internalizing disorder symptoms. Middle-of-the-night internet use (midnight–5 am) was associated with a later bedtime, shorter total sleep time, and more internalizing disorder symptoms. Adolescents used the internet to fulfill social needs, to avoid or combat boredom, or for maladaptive activities. Using the internet for social interaction or avoidance/boredom was associated with higher internalizing disorder symptoms. Using the internet for maladaptive reasons was associated with more late-night and middle-of-the-night use. CONCLUSIONS: Adolescent internet use late at night and in the middle of the night is common. Internet use may be motivated by desires for social connection, by boredom/avoidance, or for maladaptive behaviors. Because middle-of-the-night internet use was associated with higher internalizing disorder symptoms and worse sleep, it presents as a potential target for intervention. CITATION: Asarnow LD, Gasperetti CE, Gumport NB, Harvey AG. Internet use and its impact on internalizing disorder symptoms and sleep in adolescents with an evening circadian preference. J Clin Sleep Med. 2021;17(10):2019–2027.

Cardiac magnetic resonance (CMR) findings suggesting a suspected left-dominant arrhythmogenic cardiomyopathy (LDAC) may be difficult to distinguish from those related to previous myocarditis; however, especially in patients with ventricular arrhythmias (VA) with ECG morphology consistent with a left ventricle (LV) origin differential diagnosis is fundamental. Aim of the study was to identify potential imaging features at CMR specific for LDAC diagnosis. Between January 2011 and December 2019, we enrolled 15 consecutive stable patients with a recent diagnosis of significant VA and ECG morphology consistent with a LV origin, detection of potential LV arrhythmic substrate at CMR and undergoing a clinically-indicated LV endomyocardial biopsy showing tissue abnormalities consistent with the diagnosis of LDAC. From the same CMR-endomyocardial biopsy registry, a second group of 30 consecutive patients who underwent CMR and biopsy with a histological diagnosis of previous myocarditis were identified. (1) Subepicardial LGE at the level of the posterolateral wall of the LV was detected in 13 cases of LDAC vs. 21 cases of myocarditis; (2) fat infiltration, and particularly subepicardial posterolateral fat infiltration, was found in almost all LDAC patients vs. one myocarditis only (p

Leadless pacemakers have become a major breakthrough in the management of bradyarrhythmia as an attractive alternative to the standard transvenous pacemakers, but safety and long-term outcomes of the new Micra-AV, which is capable guarantee atrioventricular (AV) synchrony, have been poorly described. Hence, we describe how we managed a 57-year-old patient who developed pacemaker syndrome due to significant Micra-AV dyssynchrony. This case emphasizes how leadless pacemaker AV synchrony could be overestimated, thereby requiring a stepwise process leading to adequate device reprogramming. Holter-ECG monitoring and exercise test resulted to be valuable tools for an early detection of inadequate AV synchrony, integrating and completing device reports.

Objectives This study aimed to assess the long-term outcomes of minimally fluoroscopic approach (MFA) compared with conventional fluoroscopic ablation (ConvA) in terms of recurrences of arrhythmia and long-term complications. Background Catheter ablation (CA) of supraventricular tachycardia (SVT) with an MFA, under the guidance of electroanatomic mapping (EAM) systems, results in a significant reduction in exposure to ionizing radiations without impairing acute procedural success and complication rate. However, data regarding long-term outcomes of MFA compared with ConvA are lacking. Methods This is a retrospective observational study. All patients undergoing MFA CA of SVT (atrioventricular nodal re-entrant tachycardia and atrioventricular re-entrant tachycardia) between 2010 and 2015 were enrolled and were compared with matched subjects (1 MFA: 2 ConvA) undergoing ConvA during the same period. The 2 co-primary outcomes were recurrence of arrhythmias and long-term complications. Results A total of 618 patients (mean age 38 ± 15 years, 60% female) were enrolled. MFA included 206 patients, whereas 412 were treated with ConvA. Acute success (99% vs. 97%; p = 0.10) and acute complications (2.4% vs. 5.3%; p = 0.14) were similar in the 2 groups. During a median follow-up of 4.4 years, 5.9% of patients experienced recurrence of arrhythmias. At multivariate analysis, ConvA (hazard ratio [HR]: 3.03) and procedural success (HR: 0.10) were independently associated with recurrence of arrhythmias. Late complications (i.e., advance atrioventricular block and need for pacemaker implantation) occurred more frequently in ConvA (3.4% vs. 0.5%; p = 0.03) compared with MFA. Conclusions CA guided by EAM systems with MFA provided better long-term results and reduced risk of complications compared with ConvA.

Coronary artery anomalies (CAAs) are a heterogeneous group of rare congenital diseases whose features and pathophysiological mechanisms are extremely variable, ranging from silent anomalies to sudden cardiac death (SCD) in the most severe cases. Although rare, congenital CAAs confer a high risk of myocardial ischemia and SCD, especially in young, previously “healthy” athletes during or immediately after vigorous exertion. Although some high-risk features that may lead to SCD have been identified, specific pathophysiological mechanisms related to SCD still remain poorly understood. When a CAA is incidentally diagnosed, optimal SCD risk stratification remains challenging, particularly in cases of anomalous aortic origin of a coronary artery arising from the opposite aortic sinus of Valsalva (ACAOS). In recent times, invasive imaging with intravascular ultrasound has gained a role in further identifying high-risk anatomic features; it has been integrated with traditional, non-invasive anatomic imaging evaluations, typically high-quality echocardiography, and cardiac magnetic resonance. Multidisciplinary programs and specific SCD risk scores should be developed in an endeavor to choose the right therapeutic approach, either clinical or interventional/surgical. Intravascular ultrasound is an extremely useful tool to evaluate vessel stenosis, even if prospective studies are still required to further validate this diagnostic strategy. In the present review, we aimed to analyze the pathophysiology and the clinical impact of ACAOS. We also summarized the predominant mechanisms for interference with normal coronary artery function, which might contribute to the onset of life-threatening arrhythmias and SCD.

AimsDesmoplakin (DSP) cardiomyopathy is an increasingly recognized form of arrhythmogenic cardiomyopathy. With a genotype-specific approach, we characterized the diagnosis, natural history, and risk for ventricular arrhythmia and heart failure in DSP cardiomyopathy.Methods and resultsWe followed 91 individuals [45 probands, 34% male, median age 27.5 years (interquartile interval 20.0–43.9)] with pathogenic or likely pathogenic DSP variants for a median of 4.3 years. Regarding the ventricular involvement, left predominance was most common (n = 22, 28%) followed by bi-ventricular in 12 (15%) and right predominance in 5 (6%). Myocardial injury (chest pain, elevated troponin, normal coronary angiogram) occurred in 20 (22%) individuals. Incidence rates of sustained ventricular arrhythmia and heart failure (ventricular dysfunction ± symptoms) were 5.9 [95% confidence interval (CI): 3.9–9.1] and 6.7 (95% CI: 4.5–9.8) per 100 person-years, respectively. In univariate regression, myocardial injury was associated with sustained ventricular arrhythmia [hazard ratio (HR) 2.53, 95% CI: 1.05–6.11] and heart failure (HR 7.53, 95% CI: 3.10–18.26). After adjustment, left ventricular ejection fraction ConclusionDSP cardiomyopathy affects both ventricles and carries high risk for ventricular arrhythmia and heart failure. Myocardial injury is associated with worse disease outcomes. Both diagnosis and risk stratification of DSP cardiomyopathy need refinement.

Cardiac involvement has been frequently reported in COVID-19 as responsible of increased morbidity and mortality. Given the importance of right heart function in acute and chronic respiratory diseases, its assessment in SARS-CoV-2 infected patients may add prognostic accuracy. Transthoracic echocardiography has been proposed to early predict myocardial injury and risk of death in hospitalized patients. This systematic review presents the up-to-date sum of literature regarding right ventricle ultrasound assessment. We evaluated commonly used echocardiographic parameters to assess RV function and discussed their relationship with pathophysiological mechanisms involved in COVID-19. We searched Medline and Embase for studies that used transthoracic echocardiography for right ventricle assessment in patients with COVID-19.

Pre-participation screening is performed to identify underlying cardiac conditions that may also lead to sudden cardiac death. Our aim is to compare submaximal Harvard Step Test (HST) with incremental Maximal Exercise Test (MET) on treadmill to induce and detect arrhythmias in younger athletes. A total of 1000 athletes (mean age 14.6 ± 4.7 years) were evaluated, 500 with MET and 500 with HST, all with continuous ECG monitoring until three minutes of recovery. Pre-test evaluation includes medical history, clinical evaluation and resting electrocardiogram. Ventricular and/or supraventricular arrhythmias were observed in 2.6% of athletes performing HST and in 8.4% during MET (p 0.001). Incidence of arrhythmias remained higher for MET also considering separately exercise phase (0.8% vs. 5.2%; p 0.001) and recovery phase (2.0% vs. 6.0%; p 0.01). No gender differences were observed. Results suggest that MET induces more arrhythmias than submaximal HST, regardless of test phase. Higher test intensity and longer exercise duration might influence test outcomes, making MET more arrhythmogenic.

Leadless pacemakers (LLPMs) have become a major breakthrough in the management of bradyarrhythmia as an attractive alternative to the standard transvenous pacemakers (TV-PMs). Recently, the introduction of a second-generation LLPMs (Micra AV-MC1AVR1) has expanded pacing modes to obtain atrioventricular (AV) synchronous pacing, providing an interesting alternative in the actual scenario of leadless pacing. Nevertheless, actual reports have highlighted some concerns regarding those devices. In this review, we sought to provide an overview of this technology based on its approval studies and major reports.

OBJECTIVE To determine if the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) improves functional impairment, psychiatric symptoms, and sleep and circadian functioning. METHOD Adults diagnosed with serious mental illness (SMI) and sleep and circadian dysfunction (N = 121) were randomly allocated to TranS-C plus usual care (TranS-C + UC; n = 61; 8 individual weekly sessions) or 6 months of Usual Care followed by Delayed Treatment with TranS-C (UC-DT; n = 60). Schizophrenia (45%) and anxiety disorders (47%) were common. Blind assessments were conducted pre-treatment, post-treatment, and 6 months later (6FU). The latter two were the post-randomization points of interest. The location was Alameda County Behavioral Health Care Services (ACBHCS), a Community Mental Health Center (CMHC) in California. RESULTS For the primary outcomes, relative to UC-DT, TranS-C + UC was associated with reduction in functional impairment (b = -3.18, p = 0.025, d = -0.58), general psychiatric symptoms (b = -5.88, p = 0.001, d = -0.64), sleep disturbance (b = -5.55, p < .0001, d = -0.96), and sleep-related impairment (b = -9.14, p < .0001, d = -0.81) from pre-treatment to post-treatment. These effects were maintained to 6-month follow-up (6FU; d = -0.42 to -0.82), except functional impairment (d = -0.37). For the secondary outcomes, relative to UC-DT, TranS-C + UC was associated with improvement in sleep efficiency and on the Sleep Health Composite score from pre-treatment to 6FU. TranS-C + UC was also associated with reduced total wake time and wake time variability from pre-treatment to post-treatment, as well as reduced hallucinations and delusions, bedtime variability, and actigraphy measured waking activity count variability from pre-treatment to 6FU. CONCLUSIONS A novel transdiagnostic treatment, delivered within a CMHC setting, improves selected measures of functioning, symptoms of comorbid disorders, and sleep and circadian outcomes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Purpose Aerobic exercise capacity is reduced in patients with chronic kidney disease, partly due to alterations at the muscular and microvascular level. This study evaluated oxygen uptake (VO2) kinetics as indicator of muscular oxidative metabolism in a population of Kidney Transplant Recipients (KTRs). Methods Two groups of KTRs enrolled 3 (n = 21) and 12 months (n = 14) after transplantation and a control group of healthy young adults (n = 16) underwent cardiopulmonary exercise testing on cycle-ergometer. The protocol consisted in two subsequent constant, moderate-load exercise phases with a final incremental test until exhaustion. Results The time constant of VO2 kinetics was slower in KTRs at 3 and 12 months after transplantation compared to controls (50.4 ± 13.1 s and 43.8 ± 11.6 s vs 28.9 ± 8.4 s, respectively; P 2 was lower in KTRs evaluated 3 months after transplantation compared to patients evaluated after 1 year (21.3 ± 4.3 and 26.4 ± 8.0 mL/kg/min; P = 0.04). Blood haemoglobin (Hb) concentration was higher in KTRs evaluated at 12 months (12.8 ± 1.7 vs 14.6 ± 1.7 g/dL; P 2 (ρ = − 0.52) and Oxygen uptake efficiency slope (OUES) (r = − 0.57) while no significant correlation with Hb and peak heart rate. Conclusions KTRs show slower VO2 kinetics compared to healthy controls. Hb and peak VO2 seem to improve during the first year after transplantation. VO2 kinetics were significantly associated with indices of cardiorespiratory fitness, but less with central determinants of aerobic capacity, thus suggesting a potential usefulness of adding this index of muscular oxidative metabolism to functional evaluation in KTRs.

Catheter-based or surgical procedures in patients with long-standing persistent atrial fibrillation (LSPAF) remain a challenge. As a result, different approaches including hybrid (surgical and endocardial) ablation have been developed. Bachmann’s bundle (BB) is a mainly epicardial structure capable of sustaining arrhythmic reentry that could be involved in the development and perpetuation of atrial fibrillation. We investigated the efficacy and safety of an adjunctive BB ablation in LSPAF patients undergoing hybrid ablation. In a two-arm non-randomized study, consecutive LSPAF patients undergoing epicardial isolation of pulmonary veins with left atrial posterior wall (box lesion) with (n = 30, BB group) and without additional BB ablation (n = 30, CONV group) were enrolled in the study. All patients underwent an endocardial procedure within 6 weeks post-surgery to assess for potential lesion gaps and additional atrial substrate modification. The primary endpoint was freedom from AF through 12 months of follow-up. The two-staged hybrid ablation was successfully completed in all patients. One-year freedom from atrial arrhythmias recurrence rates was 96.6% in the BB group vs 76.6% in the CONV group (p = 0.025). At procedure completion, 30 (100%) and 17 (56%) patients had a spontaneous cardioversion in BB and CONV group, respectively (p < 0.001). No significant differences in quality of life or complication rates were observed. This initial experience shows, for the first time, that adjunctive BB ablation in the setting of hybrid ablation for LSPAF is a feasible and effective approach in increasing maintenance of sinus rhythm without increasing complication rates.

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.

Background We sought to evaluate the additional value of left atrial appendage (LAA) 3D printing derived from computed tomography (CCT) in determining the size for LAA occlusion (LAAO) devices as compared to standard measurement by using occurrence of LAA leak as endpoint. Methods We evaluated 6 patients with LAA leak (cases) and 14 matched patients without LAA leak (controls) after LAAO. For each group, a patient-specific 3D printed model of LAA was manufactured using CT pre-operative images. The size recommended by the 3D printed model was compared with the size of the implanted device. Results Compared to the 3D printed model, 55% of the devices were underestimated, the two sizing approaches agreed in 35% of the patients, while the 3D printed model overestimated the size in 10% of patients. The prevalence of LAA leak was significantly higher in the subset of patients with underestimation of prosthesis implanted with the standard approach as compared to the other patients (p = 0.019). Conclusion 3D printing of the LAA may provide additional value to standard practice for LAAO device prosthesis sizing with the potential impact to reduce LAA leak.

Background: The outcomes of IBC pts who received NC could be different by Subtypes Methods: From 2000 to 2018 we treated 400 II-III stage IBC patients (pts) with NC. We recorded baseline characteristics, type of NC, type of surgery, pCR (defined as the absence of invasive cells in the breast and the lymph nodes regardless of DCIS), biological features of RT. pCR and survival outcomes (in term of Disease Free Survival-DFS, Relapse Free Survival-RFS and Overall Survival-OS) also on the basis of both pre- and post- NC Ki67 levels were assessed Results: Median age was 50 yrs (r. 25-75). Population consisted of: Luminal A (LA): 3.7% Luminal B (LB): 28.25% Luminal HER2 (LHER2): 28% HER2+HR- 13.5% Triple Negative (TN):21.25% Unknown:5.3% The NC was based on tri-weekly or dose-dense (only 22 cases) anthracyclines (A) followed by weekly taxanes (T) in HER2- (249), associated with weekly carboplatin (C) in more recent cases (48) of TN and T + trastuzumab (H) ± A (40) or C (102) in HER2+ pts. All pts but 18 did received surgery: 8 for distant metastases occurrence and 10 because still on NC. Quadrantectomy was performed in 205(52%) pts. pCR was achieved in 125 (31%) pts of which 30 with non invasive residual; further 10 patients showed RT ≤1 mm Relationship between pCR and SubtypesLA (%)LB (%)LHER2 (%)HER2+HR-TN (%)pCR6.715.938.450.041.2No pCR93.384.161.650.058.8p Value pCR was reached in 41.5% in case of proliferation index by Ki67 ≥ 20% and in particular if > ki67 was > 40% regardless of Subtypes (p=0.001). All 166 HER2 + patients except 24 received H obtaining pCR in 70 (45.8%) of cases regardless chemotherapy type. pCR were 30.7% and 50% according to A- vs C-based regimen respectively. Twenty-six of 48 TN pts receiving C addition underwent S with pCR. The median Fup was 44.12 months (r: 1.35-232.6). The pCR was positively associated with DFS (HR 0.17, 95% CI 0.07-0.40), RFS (HR 0.26, 95% CI 0.13-0.50) and OS (HR 0.17, 95% CI 0.06-0.49) in overall population The association between pCR and long-term outcomes (DFS and RFS, but not OS) was greater in TN pts (EFS: HR 0.11, 95% CI 0.01-0.90; RFS: 0.12, 95% CI 0.06-0.71), in LHER2 (EFS: HR 0.20, 95% CI 0.04-0.87; RFS: 0.24, 95% CI 0.07-0.84) and in HER2+ (EFS: HR 0.11, 95% CI 0.01-0.90; RFS: 0.24, 95% CI 0.06-0.73) than in LA and LB. Postoperative low level of Ki67 (< 10%) reduced the risk of both relapse (HR = 0.37 ci 0.17-0.76) and death (HR = 0.29 ci 0.12-0.70) compared with pts with higher Ki67 levels. Conclusions: The pCR rate was significantly higher in aggressive Subtypes (HER2+ and TN) than luminals. Pts achieving pCR showed better RFS and OS compared to no pCR pts. Interestingly high pre-NC PI seems to predict the possibility obtaing pCR, while post-NC PI seems to be of prognostic value in pts who do not receive pCR, in particular in LB subtypes. Citation Format: Antonella Ferro, Alessia Caldara, Elisabetta Grego, Carlo Messina, Gabriella Berlanda, Paolo Cristofolini, Fabio Gasperetti, Salvatore Mussari, Carmine Fantò, Marvi Valentini, Marco Pellegrini, Mattia Barbareschi, Nicola Mirabassi, Giuseppe Carbone, Roberta Biondi, Renza Triolo, Silvia Lazzeri, Vincenzo Sabatino, Paola Bondioli, Orazio Caffo. Impact of pathologic complete response (pCR) and and biological features of residual tumor (RT) on prognosis after neoadjuvant chemotherapy (NC) in various invasive breast cancer (IBC) subtypes [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-24.

Aims In arrhythmogenic cardiomyopathy (ACM), sustained ventricular tachycardia (VT) typically displays a left bundle branch block (LBBB) morphology while a right bundle branch block (RBBB) morphology is rare. The present study assesses the VT morphology in ACM patients with sustained VT and their clinical and genetic characteristics. Methods and results Twenty-six centres from 11 European countries provided information on 954 ACM patients who had ≥1 episode of sustained VT spontaneously documented during patients’ clinical course. Arrhythmogenic cardiomyopathy was defined according to the 2010 Task Force Criteria, and VT morphology according to the QRS pattern in V1. Overall, 882 (92.5%) patients displayed LBBB-VT alone and 72 (7.5%) RBBB-VT [alone in 42 (4.4%) or in combination with LBBB-VT in 30 (3.1%)]. Male sex prevalence was 79.3%, 88.1%, and 56.7% in the LBBB-VT, RBBB-VT, and LBBB + RBBB-VT groups, respectively (P = 0.007). First RBBB-VT occurred 5 years after the first LBBB-VT (46.5 ± 14.4 vs 41.1 ± 15.8 years, P = 0.011). An implanted cardioverter-defibrillator was more frequently implanted in the RBBB-VT (92.9%) and the LBBB + RBBB-VT groups (90%) than in the LBBB-VT group (68.1%) (P Conclusion RBBB-VT accounts for a significant proportion of sustained VTs in ACM. Sex and type of pathogenic mutations were associated with VT type, female sex with LBBB + RBBB-VT, and DSP mutation with RBBB-VT.

Despite advances in treatment, bipolar disorders (BP) remain severe and chronic conditions associated with high rates of relapse, marked functional impairment, and disabling symptoms, even between syndromal episodes. Sleep dysfunctions are among the most prominent correlates of mood episodes and inadequate recovery. Sleep disturbance in BP impairs quality of life and contributes to relapse and serious impairment in affect regulation, cognitive performance, and health. This chapter describes the process of adapting cognitive behavior therapy for insomnia (CBT-I) for BP. In addition, we describe how this resulted in moving from a disorder-focused approach to a transdiagnostic approach. This long-term objective is to contribute to ensuring that treatments for sleep and circadian problems for BP and severe mental illness are disseminable and widely available to the public.

Background Ventricular arrhythmias (VAs) represent a critical issue with regard to sports eligibility assessment in athletes. The ideal diagnostic evaluation of competitive and leisure-time athletes with complex VAs has not been clearly defined. Objective The purpose of this study was to assess the clinical implications of invasive electrophysiological assessments and endomyocardial biopsy (EMB) among athletes with VAs. Methods We evaluated 227 consecutive athletes who presented to our institutions after being disqualified from participating in sports because of VAs. After noninvasive tests, electrophysiological study (EPS), electroanatomic mapping (EAM), and EAM- or cardiac magnetic resonance imaging–guided EMB was performed, following a prespecified protocol. Sports eligibility status was redefined at 6-month follow-up. Results From our sample, 188 athletes (82.8%) underwent EAM and EPS, and 42 (15.2%) underwent EMB. A diagnosis of heart disease could be formulated in 30% of the study population (67/227; 95% confidence interval [CI] 0.24–0.36) after noninvasive tests; in 37% (83/227; 95% CI 31%–43%) after EPS and EAM; and in 45% (102/227; 95% CI 39%–51%) after EMB. In the subset of athletes undergoing EMB, invasive diagnostic workup allowed diagnostic reclassification of half of the athletes (n = 21 [50%]). Reclassification was particularly common among subjects without definitive findings after noninvasive evaluation (n = 23; 87% reclassified). History of syncope, abnormal echocardiogram, presence of late gadolinium enhancement, and abnormal EAM were linked to sports ineligibility at 6-month follow-up. Conclusion A comprehensive invasive workup provided additional diagnostic elements and could improve the sports eligibility assessment of athletes presenting with VAs. The extensive invasive evaluation presented could be especially helpful when noninvasive tests show unclear findings.

Background: We aim to evaluate the value of Cardiac magnetic resonance (CMR) feature tracking (CMR-FT) in addition to Task Force Criteria(TFC) in patients with (arrhythmogenic cardiomyopathy) AC biopsy-proved. Methods: Thirty-five patients with AC histologically proven who performed CMR with late gadolinium enhancement (LGE) acquisition were enrolled. The study population was divided in Group1 (negative CMR TFC and LV ejection fraction≥55%) and Group2 (positive CMR TFC and/or LVEF

Background:Arrhythmogenic left ventricular cardiomyopathy (ALVC) is an under-characterized phenotype of arrhythmogenic cardiomyopathy involving the LV ab initio. ALVC was not included in the 2010 International Task Force Criteria for arrhythmogenic right ventricular cardiomyopathy diagnosis and data regarding this phenotype are scarce.Methods:Clinical characteristics were reported from all consecutive patients diagnosed with ALVC, defined as a LV isolated late gadolinium enhancement and fibro-fatty replacement at cardiac magnetic resonance plus genetic variants associated with arrhythmogenic right ventricular cardiomyopathy and of an endomyocardial biopsy showing fibro-fatty replacement complying with the 2010 International Task Force Criteria in the LV.Results:Twenty-five patients ALVC (53 [48–59] years, 60% male) were enrolled. T wave inversion in infero-lateral and left precordial leads were the most common ECG abnormalities. Overall arrhythmic burden at study inclusion was 56%. Cardiac magnetic resonance showed LV late gadolinium enhancement in the LV lateral and posterior basal segments in all patients. In 72% of the patients an invasive evaluation was performed, in which electroanatomical voltage mapping and electroanatomical voltage mapping-guided endomyocardial biopsy showed low endocardial voltages and fibro-fatty replacement in areas of late gadolinium enhancement presence. Genetic variants in desmosomal genes (desmoplakin and desmoglein-2) were identified in 12/25 of the cohort presenting pathogenic/likely pathogenic variants. A definite/borderline 2010 International Task Force Criteria arrhythmogenic right ventricular cardiomyopathy diagnosis was reached only in 11/25 patients.Conclusions:ALVC presents with a preferential involvement of the lateral and postero-lateral basal LV and is associated mostly with variants in desmoplakin and desmoglein-2 genes. An amendment to the current International Task Force Criteria is reasonable to better diagnose patients with ALVC.

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.

The overshoot of the respiratory exchange ratio (RER) during recovery from exercise has been found to be reduced in magnitude among patients with heart failure. The aim of this study is to investigate whether this phenomenon could also be present in patients with peripheral, and not cardiac, limitations to exercise such as kidney transplant recipients (KTRs). In this retrospective cross-sectional study, KTRs were evaluated with maximal cardiopulmonary exercise testing (CPET) assessing the RER overshoot parameters during recovery: the RER at peak exercise, the maximum RER value reached during recovery, the magnitude of the RER overshoot (RER mag = (RER max-peak RER)/peak RER%) and the linear slope of the RER increase after the end of exercise. A total of 57 KTRs were included in the study (16 females), all of them showing a significant RER overshoot (RER mag: 28.4 ± 12.7%). Moreover, the RER mag showed significant correlations with the fitness of patients (peak VO2: ρ = 0.57, p &lt, 0.01) and cardiorespiratory efficiency (VE/VCO2 slope: r = −0.32, p &lt, 0.05, oxygen uptake efficiency slope (OUES): r = 0.48, p &lt, 0.01). Indeed, the RER mag was significantly different between the subgroups stratified by Weber’s fitness class or a ventilatory efficiency class. Our study is the first to investigate recovery of the RER in a population of KTRs, which correlates well with known prognostic CPET markers of cardiorespiratory fitness, determining the RER mag as the most meaningful RER overshoot parameter. Thus, the RER recovery might be included in CPET evaluations to further improve prognostic risk stratifications in KTRs and other chronic diseases.

Aims Balloon-based technologies have been developed to simplify catheter ablation of atrial fibrillation (AF), to improve the clinical outcome of the procedure and to achieve durable pulmonary vein isolation (PVI). The objective of this study is to evaluate the safety and efficacy of second-generation laser balloon (LB2) ablation in the treatment of AF using a continuous cardiac rhythm monitoring strategy. Atrial tachyarrhythmias (ATas) recurrences were assessed with implantable cardiac monitors (ICMs) or devices. Methods and results All patients underwent LB2 ablation procedure. The primary endpoint was the first recurrence of any, >5.5 and >24 h duration ATas after the blanking period (90 days). In-hospital visits were performed at 3, 6, and 12 months. Seventy-three patients (68% male, mean age 59.8 ± 11.3) were included in the study. The average procedure, fluoroscopy, and laser ablation times were 81.5 ± 30.1, 21.5 ± 12.4, and 33.8 ± 9.7, respectively. All PVs were isolated using the LB2 with no need of touch-up using focal catheters. No major complications occurred during or after the procedures. The one-year freedom from recurrences was 66.9% (95% CI: 57.0–76.7%), 81.0% (69.5–88.5%), and 86.8% (76.1–92.9%) considering any, 5.5-h and 24-h cut-off duration, respectively. At 3, 6, and 12 months, any ATas was recorded in 22%, 32%, and 25% of patients, with a ≥5% arrhythmic burden documented in 4%, 5%, and 3%, respectively. Few patients reported AF-related symptoms (7%, 8%, and 5%). Conclusion LB2 ablation is a safe and effective procedure, showing a high freedom from recurrences and low arrhythmic burden as documented by a continuous rhythm monitoring strategy.

Complete atrioventricular block (CAVB) is a total dissociation between the atrial and ventricular activity, in the absence of atrioventricular conduction. Several diseases may result in CAVB in the pediatric and young-adult population. Permanent right ventricular (RV) pacing is required in permanent CAVB, when the cause is neither transient nor reversible. Continuous RV apical pacing has been associated with unfavorable outcomes in several studies due to the associated ventricular dyssynchrony. This study aims to summarize the current literature regarding CAVB in the pediatric and young adult population and to explore future treatment perspectives.

Severe acute respiratory syndrome coronavirus 2 infection in children mainly shows a milder course. In complicated cases, it is unknown whether inflammation is predictive of disease severity, as in adults. Moreover, cardiac involvement is anecdotally described. We report the case of a 2-month-old infant with severe acute respiratory syndrome coronavirus 2 infection presenting with fever, tachycardia and elevated interleukin-6, who was diagnosed with myocarditis and treated with immunoglobulins.

BACKGROUND Multipoint pacing (MPP) may improve clinical outcomes in patients with cardiac resynchronization therapy defibrillators (CRT-D), but its impact on battery longevity in a real-world population has not been investigated in large trials. OBJECTIVE Compare projected battery longevity in CRT-D patients with and without MPP during long-term follow-up. METHODS The Italian registry on multipoint left ventricular pacing (IRON-MPP) is a prospective, multicenter registry of patients implanted with MPP-capable CRT-D devices. Projected battery longevity during follow-up was compared for patients with MPP (MPP ON) vs single-site (MPP OFF) left ventricular pacing at CRT-D implantation. A sub-analysis excluded crossover patients with MPP activation or deactivation occurring after implantation. A second sub-analysis excluded patients with a right or left ventricular pacing amplitude >2.5 V. RESULTS Out of 237 CRT-D patients (71 ± 9 years, 81% male) followed for 1.9 ± 0.8 years, 102 (43%) had MPP ON at implantation. Programmed atrial and ventricular outputs and percentage of pacing were similar between groups. MPP was associated with a 0.44 years reduction in projected battery longevity (P = .03) during long-term follow-up. Results were similar for the first and second sub-analyses, with a 0.57 years (P

Background The combined left atrial appendage closure (LAAC) and cryoenergy pulmonary vein isolation (PVI) procedure has been proven safe and effective in managing stroke in patients with nonvalvular atrial fibrillation (AF), although most data refer to procedures performed using radiofrequency as the main energy source. Objective The purpose of this study was to evaluate long-term follow-up of patients with AF undergoing concomitant LAAC and cryoenergy PVI. Methods Patients undergoing LAAC and cryoballoon PVI at our institution were enrolled. At 3, 6, and 24 months from the index procedure, we determined the atrial arrhythmia recurrence rate, the extent of LAAC, and the rate of cerebrovascular/bleeding events. Results Forty-nine patients (mean age 69 ± 8 years; 32/49 (67%) men; CHA2DS2-VASc score 2.8 ± 1.2; HAS-BLED score 3 ± 1) with a guideline-recommended LAAC indication were included. Acute PVI and complete LAAC were achieved in 100% of patients. All patients completed at least 24 months of follow-up. At 8 weeks and 6 months, complete or satisfactory ( Conclusion Concomitant cryoballoon ablation and LAAC procedures appear safe and effective at long-term follow-up, with high antithrombotic drug withdrawal rates at 24 months.

Total-body irradiation causes acute and delayed toxicity to hematopoietic, pulmonary, cardiac, gastrointestinal, renal, and other organ systems. Angiotensin-converting enzyme inhibitors mitigate many of the delayed injuries to these systems. The purpose of this study was to define echocardiographic features in rats at two times after irradiation, the first before lethal radiation pneumonitis (50 d) and the second after recovery from pneumonitis but before lethal radiation nephropathy (100 d), and to determine the actions of the angiotensin-converting enzyme inhibitor lisinopril. Four groups of female WAG/RijCmcr rats at 11-12 wk of age were studied: nonirradiated, nonirradiated plus lisinopril, 13-Gy partial-body irradiation sparing one hind leg (leg-out partial-body irradiation), and 13-Gy leg-out partial-body irradiation plus lisinopril. Lisinopril was started 7 d after radiation. Echocardiograms were obtained at 50 and 100 d, and cardiac histology was assessed after 100 d. Irradiation without lisinopril demonstrated echocardiographic transient pulmonary hypertension by 50 d which was largely resolved by 100 d in survivors. Irradiated rats given lisinopril showed no increase in pulmonary artery pressures at 50 d but exhibited left ventricular remodeling. By 100 d these rats showed some signs of pulmonary hypertension. Lisinopril alone had no impact on echocardiographic end points at either time point in nonirradiated rats. Mild increases in mast cells and fibrosis in the heart were observed after 100 d following 13-Gy leg-out partial-body irradiation. These data demonstrate irradiation-induced pulmonary hypertension which was reversed in survivors of pneumonitis. Lisinopril modified cardiovascular remodeling to enhance survival in this model from 41% to 86% (p = 0.0013).

Background Nowadays, transvenous lead extraction (TLE) is considered an essential technique in lead management strategy. Since 2011, a multidisciplinary approach was undertaken in our centre involving electrophysiologists, cardiac surgeons and anaesthesiologists to improve cross- unit cooperation and minimize complications and mortality. The present paper reports procedural outcomes and complications of our lead extraction experience. Methods We retrospectively collected and analysed data from all consecutive patients undergoing cardiac implantable electronic device leads TLE at the IRCCS Centro Cardiologico Monzino between January 2011 and November 2017. Results One-hundred fifty patients (111 males, 68 ± 13 years) underwent extraction procedures. The most common extraction indication were infections (86.7%) and TLE was carried out by laser-based approach in 88 (58.6%) patients, by mechanical dilating sheaths in 58 (38.7%) patients and by a combined approach (TLE + open surgical intervention) in 4 (2.7%) patients. Procedural success was obtained in 146 (97.3%) cases with only 3 (2.0%) major complications with 2 cases of structural injury with tamponade requiring emergent median sternotomy. Open surgery extraction was required in 4 patients, after an attempt to TLE, due to leads strict adhesion to cardiac or vascular structures, whereas in 5 (3.3%) cases, the treatment of choice was a combined approach consisting in transvenous leads extraction followed by planned surgery. Conclusions TLE is a complex procedure that sometimes leads to fatal complications. In our single center experience, a multidisciplinary approach involving electrophysiologist, cardiac surgeon, anaesthesiologist in an operating room allows a safer approach and major complications treatment.

Background To date, only a few comparisons between subcutaneous implantable cardioverter-defibrillator (S-ICD) patients undergoing and those not undergoing defibrillation testing (DT) at implantation (DT+ vs DT–) have been reported. Objective The purpose of this study was to compare long-term clinical outcomes of 2 propensity-matched cohorts of DT+ and DT– patients. Methods Among consecutive S-ICD patients implanted across 17 centers from January 2015 to October 2020, DT– patients were 1:1 propensity-matched for baseline characteristics with DT+ patients. The primary outcome was a composite of ineffective shocks and cardiovascular mortality. Appropriate and inappropriate shock rates were deemed secondary outcomes. Results Among 1290 patients, a total of 566 propensity-matched patients (283 DT+; 283 DT–) served as study population. Over median follow-up of 25.3 months, no significant differences in primary outcome event rates were found (10 DT+ vs 14 DT–; P = .404) as well as for ineffective shocks (5 DT– vs 3 DT+; P = .725). At multivariable Cox regression analysis, DT performance was associated with a reduction of neither the primary combined outcome nor ineffective shocks at follow-up. A high PRAETORIAN score was positively associated with both the primary outcome (hazard ratio 3.976; confidence interval 1.339–11.802; P = .013) and ineffective shocks alone at follow-up (hazard ratio 19.030; confidence interval 4.752–76.203; P = .003). Conclusion In 2 cohorts of strictly propensity-matched patients, DT performance was not associated with significant differences in cardiovascular mortality and ineffective shocks. The PRAETORIAN score is capable of correctly identifying a large percentage of patients at risk for ineffective shock conversion in both cohorts.

For decades, the cardiogenic shock has remained one of the cardiac illnesses with the highest mortality, as high as 50%. Recent advances have lowered this mortality rate by use of early recognition of shock as well as an increased understanding of both advanced mechanical support and the hemodynamics of myocardial support. Included are the new definition of shock, results of a study of inotropic medications in shock, description, and case studies of mechanical circulatory support, all providing a framework for the overall goal in the management of cardiogenic shock as one to recognize shock, follow its dynamic state, and maximize support to patients toward recovery.

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

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): The Zurich ACM Program is supported by generous grants from the Georg and Bertha Schwyzer-Winniker Foundation, the Baugarten Foundation, Swiss National Science Foundation, Swiss Heart Foundation and Wild Foundation. This work is also supported by a Canadian Institutes of Health Research grant (FRN: 162402) and the Labatt Heart Centre and Waugh Family Innovation Funds, Caitlin Elizabeth Morris Memorial Fund, Alex Corrance Memorial Foundation and Meredith Cartwright. BACKGROUND Arrhythmogenic right ventricular cardiomyopathy (ARVC) has several phenocopies such as cardiac sarcoidosis (CS), idiopathic outflow tract ventricular tachycardia (OT-VT) and myocarditis. Differentiation between these entities can be challenging. Recently, we have identified diagnostic anti-desmoglein-2 autoantibodies (anti-DSG2 Abs) in patients with ARVC. PURPOSE We sought to examine whether anti-DSG2 Abs are also present in clinical phenocopies of ARVC. METHODS Anti-DSG2 Abs in sera of 25, 19 and 22 patients with sarcoidosis, OT-VT and myocarditis, respectively, were assessed by western blots and ELISA. Clinical and imaging parameters, as well as conventional biomarkers were correlated to detected anti-DSG2 Ab intensity levels. RESULTS Anti-DSG2 Abs, at various intensities, were identified in 6/25 (24%) patients with sarcoidosis, all presenting with CS, but were absent in patients with OT-VT and myocarditis. Cardiac 18F- fluorodeoxyglucose positron emission tomography (18F-FDG PET) was positive in all sarcoidosis patients with positive anti-DSG2 Abs, corresponding to a median PET maximum standardized uptake value (SUVmax) of 5.65 [IQR: 5.15 – 10.9]. In sarcoidosis patients without anti-DSG2 Abs, the SUVmax values were significantly lower with a median of 0 [IQR: 0 – 4] (p = 0.011). The Pearson correlation coefficient (R) was 0.188 (p = 0.039) indicating a positive correlation between cardiac 18F-FDG uptake and anti-DSG2 Abs. No significant correlation was detected for any of the other clinical parameters and biomarkers. CONCLUSIONS In addition to being present in ARVC, anti-DSG2 Abs are also found in CS, a common phenocopy of ARVC; conversely, anti-DSG2 Abs are absent in idiopathic OT-VT and myocarditis. Anti-DSG2 Ab levels positively correlate with myocardial disease activity in CS as indicated by cardiac 18F-FDG PET scanning. Abstract Figure. Central illustration

Background Endomyocardial biopsy (EMB) is part of 2010 Task Force Criteria (TFC) for arrhythmogenic right ventricular cardiomyopathy (ARVC). However, its usage has been curtailed because of its low presumed diagnostic yield, and it is now a poorly used tool. This study aims to analyze the contribution of EMB to the final diagnosis of ARVC. Methods and Results We included 104 consecutive patients evaluated for a suspicion of ARVC, who were referred for EMB. Patients with suspected left dominant pattern were excluded from the primary analysis. Subjects were initially stratified according to TFC without considering EMB. After EMB, patients were reclassified accordingly, and the reclassification rate was calculated. EMB yielded a diagnostic finding in 92 patients (85.5%). After including EMB evaluation, 20 (43%) more patients “at risk” received a definite diagnosis of ARVC. Overall, 59 patients received a definite diagnosis of ARVC, 34% only after EMB. EMB appeared to be the better‐performing exam with respect to the final diagnosis (β, 2.2; area uder the curve, 0.73; P P Conclusions Electroanatomic voltage mapping–guided EMB was safe and yielded an optimal diagnostic yield. It allowed upgrading of the diagnosis of nearly one‐third of the patients considered “at risk.” Classical TFC without EMB performed poorly in patients with the left dominant form of ARVC.

Different approaches are used to classify obesity severity. Beyond classical anthropometric measurements, the Edmonton Obesity Staging System (EOSS) considers medical, physical and psychological parameters. However, this method has some limitations, principally due to the absence of an objective measure for physical impairment. The aim of our study is thus to overcome this limitation suggesting a new functional parameter obtained by cardiopulmonary exercise testing (CPET), i.e., cardiorespiratory fitness (CRF), expressed as weight-adjusted peak oxygen consumption (VO2peak/kg). This observational cross-sectional study conducted on a population of 843 patients affected by obesity finally enrolled 500 subjects. Every patient underwent clinical, anthropometric, biochemical assessment and CPET. First, participants have been classified according to standard EOSS in five stages. Second, patients were reclassified according to the new modified EOSS (EOSS-CRF) based on their age- and gender-appropriate VO2peak/kg percentiles as reported in the healthy normal-weight population of the FRIEND registry. VO2peak/kg was significantly different between standard EOSS classes 1 and 2 and classes 1 and 3 (ANCOVA p model = 0.004), whereas patients in classes 2 and 3 showed similar CRF. The EOSS-CRF classification varied in number of patients in each class compared to EOSS, particularly with a shift from class 2 to class 3. Moreover, CRF showed that physical impairment is less addressed by EOSS when compared to EOSS-CRF. The integration of EOSS with CRF allowed us to assign to each patient a severity index that considers not only clinical parameters, but also their functional impairment through a quantitative and prognostically important parameter (VO2peak/kg). This improvement of the staging system may also provide a better approach to identify individuals at increased risk of mortality leading to targeted therapeutic management and prognostic risk stratification for patients with obesity.

Proper investment in mushroom production (farming and wild mushroom picking activities) may represent a winning strategy for many countries, including Italy, to better face the problems of food security and environmental impact, and to break away from imports, enhancing the local products. However, the risk related to the consumption of poisoning species requires governments to implement or reinforce effective control measures to protect consumers. Mushroom identification by phenotype observation is hardly applicable if morphologically-similar species, non-whole specimens, or clinical samples are involved. Genotypic analysis is a valid alternative. An ongoing research project involving the Experimental Zooprophylactic Institute of Lazio and Tuscany, the regional Mycological Inspectorate, the Tuscany Mycological Groups Association, and the Department of Veterinary Sciences of the University of Pisa aims to reinforce the collaboration among institutions for the management of mushroom poisoning. The core’s project aims to develop an internal genetic database to support the identification of wild and cultivated mushroom species in the Italian territory. The database will include Internal Transcribed Spacer (ITS) sequences retrieved from official databases (the NCBI GenBank and the BOLD system) which are considered to be reliable, after a proper selection process, and sequences from specimens collected directly and identified by expert mycologists. Once it is validated, the database will be available and further implementable by the official network of national laboratories.

Background Electrocardiographic (ECG) pre-participation screening(PPS) can prevent sudden cardiac death(SCD) but the Interpretation of the athlete's ECG is based on specific criteria addressed for adult athletes while few data exist about the pediatric athlete's ECG. We aimed to assess the features of pediatric athletes' ECG and compared the diagnostic performance of 2017 International ECG recommendation, 2010 European Society of Cardiology recommendation and 2013-Seattle criteria in detecting clinical conditions at risk of SCD. Methods 886 consecutive pediatric athletes (mean age 11.7 ± 2.5 years; 7–16-years) were enrolled and prospectively evaluated with medical history, physical examination, resting and exercise ECG and transthoracic echocardiography during their PPS. Results The most common physiological ECG patterns in pediatric athletes were isolated left ventricular hypertrophy criteria (26.9%), juvenile T-wave pattern (22%) and early repolarization pattern (13.2%). The most frequent borderline abnormalities were left axis deviation (1.8%) and right axis deviation (0.9%) while T-wave inversion (0.8%) especially located in inferior leads (0.7%) was the most prevalent abnormal findings. Seven athletes (0.79%) were diagnosed with a condition related to SCD. Compared to Seattle and ESC, the International improved ECG specificity (International = 98% ESC = 64% Seattle = 95%) with lower sensitivity (ESC and Seattle 86%vs International 57%). The false-positive rate decreases from 36% of ESC to 2.2% of International but the latter showed a higher false-negative rate(0.34%). Conclusion Pediatric athletes like the adult counterpart exhibit a high prevalence of ECG abnormalities mostly representing training-related ECG adaptation. The International criteria showed a lower false-positive rate but at the cost of loss of sensitivity.

In the early stages of COVID-19 pneumonia, hypoxemia has been described in absence of dyspnea ("silent" or "happy" hypoxemia). Our aim was to report its prevalence and outcome in a series of hypoxemic patients upon Emergency Department admission.In this retrospective observational cohort study we enrolled a study population consisting of 213 COVID-19 patients with PaOinf2/inf/FiOinf2/infratio300 mmHg at hospital admission. Two groups (silent and dyspneic hypoxemia) were defined. Symptoms, blood gas analysis, chest X-ray (CXR) severity, need for intensive care and outcome were recorded.Silent hypoxemic patients (68-31.9%) compared to the dyspneic hypoxemic patients (145-68.1%) showed greater frequency of extra respiratory symptoms (myalgia, diarrhea and nausea) and lower plasmatic LDH. PaOinf2/inf/FiOinf2/infratio was 225±68 mmHg and 192±78 mmHg in silent and dyspneic hypoxemia respectively (P=0.002). Eighteen percent of the patients with PaOinf2/inf/FiOinf2/inffrom 50 to 150 mmHg presented silent hypoxemia. Silent and dyspneic hypoxemic patients had similar PaCOinf2/inf(34.2±6.8 mmHg vs. 33.5±5.7 mmHg, P=0.47) but different respiratory rates (24.6±5.9 bpm vs. 28.6±11.3 bpm respectively, P=0.002). Even when CXR was severely abnormal, 25% of the population was silent hypoxemic. Twenty-six point five percent and 38.6% of silent and dyspneic patients were admitted to the ICU respectively (P=0.082). Mortality rate was 17.6% and 29.7% (log-rank P=0.083) in silent and dyspneic patients.Silent hypoxemia is remarkably present in COVID-19. The presence of dyspnea is associated with a more severe clinical condition.

Multiple studies have addressed the importance of anteroseptal scar in patients with nonischemic cardiomyopathy. However, this pattern has never been fully evaluated in patients with prior myocarditis.The purpose of this study was to evaluate whether anteroseptal scar is associated with worse outcome in patients with prior myocarditis and how it affects the efficacy of catheter ablation (CA).This was a retrospective study of consecutive patients with prior myocarditis and arrhythmic presentation. Cardiac magnetic resonance and electroanatomic voltage mapping were used to identify the scar pattern. Patients were referred for either CA or escalated antiarrhythmic drug (AAD) therapy. The main outcome was ventricular arrhythmia (VA)-free survival according to the presence of anteroseptal scar.A total of 144 consecutive patients with prior myocarditis were included. Mean age was 42.1 ± 14.9 years, and 58% were men. Ejection fraction was normal in 73% of patients. Anteroseptal scar was present in 44% of cases. Sixty-one patients (42%) underwent CA. Overall, at 2-year follow-up, VA-free survival was 77% in the CA group. After CA, the mean number of AADs taken by each patient decreased from 1.8 to 0.9 per day (p0.001). The presence of anteroseptal scar was found to be an independent predictor of VA relapse both in patients treated with CA (hazard ratio [HR] 3.6; 95% confidence interval [CI] 1.1-11.4; P = .03) and in the overall population (HR 2.0; 95% CI 1.2-3.5; P = .02) .In patients with prior myocarditis and VA, the presence of anteroseptal scar negatively predicts outcomes irrespective of treatment strategy.

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.

Background: Percutaneous left atrial appendage closure (LAAC) requires accurate pre- and intraprocedural measurements, and multimodality imaging is an essential tool for guiding the procedure. Two-dimensional (2D TOE) and three-dimensional (3D TOE) transoesophageal echocardiography, cardiac computed tomography (CCT), and conventional cardiac angiography (CCA) are commonly used to evaluate left atrial appendage (LAA) size. However, standardized approaches in measurement methods by different imaging modalities are lacking. The aims of the study were to evaluate the LAA dimension and morphology in patients undergoing LAAC and to compare data obtained by different imaging modalities: 2D and 3D TOE, CCT, and CCA. Methods: A total of 200 patients (mean age 70 ± 8 years, 128 males) were examined by different imaging techniques (161 2D TOE, 103 3D TOE, 98 CCT, and 200 CCA). Patients underwent preoperative CCT and intraoperative 2D and 3D TOE and CCA. Results: A significant correlation was found among all measurements obtained by different modalities. In particular, 3D TOE and CCT measurements were highly correlated with an excellent agreement for the landing zone (LZ) dimensions (LZ diameter: r = 0.87; LAA depth: r = 0.91, p < 0.001). Conclusions: Head-to-head comparison among imaging techniques (2D and 3D TOE, CCT, and CCA) showed a good correlation among LZ diameter measurements obtained by different imaging modalities, which is a parameter of paramount importance for the choice of the LAAC device size. LZ diameters and area by 3D TOE had the best correlation with CCT.

Introduction: Catheter ablation is superior to drugs regarding atrial fibrillation (AF) recurrence, symptoms improvement, and mortality reduction in heart failure. POLARx™ is a novel cryoballoon, with technical improvements seeking to improve outcomes. So far, its clinical evidence is restricted to a case report. Methods: To compare the POLARx™ cryoballoon procedural safety and efficacy to the already established Arctic Front Advance PRO™ (AFAP) in a single-center cohort study, consecutive patients undergoing AF cryoablation with the POLARx™ were enrolled. Data were prospectively gathered. POLARx™ patients were compared to a historical cohort of patients submitted to AF cryoablation with the AFAP. Results: Seventy patients were analyzed, 20 in POLARx™, and 50 in the AFAP group. They all underwent first-time pulmonary vein isolation, 77% were male, 94% had paroxysmal AF, median age was 62.5 years, median CHA2DS2-VASc 1, left-atrium size 34ml/m², and 65% were receiving anticoagulation. The primary end-point, all pulmonary veins isolation, was 100% in both groups. The complication rate was similar (0% POLARx™ vs. 5.7% AFAP, p=0.39). The median total procedural time was longer in the POLARx™ group (90min vs. 60min, p

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.

Introduction Cardiac sarcoidosis (CS) is an inflammatory granulomatous disease of unknown origin. CS and arrhythmogenic right ventricular cardiomyopathy (ARVC) are overlapping syndromes. With both, patients are at increased risk of ventricular arrhythmias and sudden cardiac death. However, the diagnosis of CS is challenging, especially in patients with no extracardiac involvement, but correct diagnosis has large therapeutic impact. Recently, a novel diagnostic autoantibody (anti-DSG2 Ab) was identified in ARVC. We sought to identify this antibody in CS patients and correlate its levels with inflammation activity using cardiac positron-emission-tomography (18-FDG-PET). Methods Recombinant human desmoglein-2 (DSG2) proteins on western blots were exposed to sera as well as purified IgG of 14 patients with sarcoidosis (all confirmed by histology) and 6 controls (1 ARVC patient (positive control) and 5 healthy control subjects (negative control)). Clinical patient characteristics were correlated to detected antibody intensity levels. Results The sarcoidosis cohort comprised 43% (6/14) male patients and the average age was 50±12 years. Anti-DSG2 Abs were identified in 43% (6/14) and were detected faintly (below cut off level) in 21% (3/14) of all sarcoidosis patients. Antibody was also present in the ARVC patient (1/1) and was absent in all control subjects (5/5). Myocardial inflammation was present in 18-FDG PET imaging in all CS patients with positive anti-DSG2 Abs, corresponding to an average SUV (standardized uptake value) of 8.1±4.2. In patients with faint or no antibody, the SUV values were significantly lower with 1.2±2.1 and 3.2±4.0, respectively (P=0.044, one-way ANOVA). The Pearson correlation coefficient (R) was 0.6 (P=0.037) for SUV vs. higher antibody levels assessed by pixel count of the western blot bands for purified IgG. Conclusions Anti-DSG2 Abs are not only a specific biomarker for ARVC, but are also found in CS, suggesting a similar pathophysiological mechanism in these overlapping syndromes, both involving cardiac inflammation and myocyte cell death. Moreover, antibody levels correlate with disease activity on cardiac PET imaging. Larger cohorts are necessary to confirm these findings. Funding Acknowledgement Type of funding source: None

Introduction Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically inherited disease characterized by fibro-fatty infiltrations (FFI). FFI in ARVC patients usually originates in the ventricles, but recent imaging studies showed FFI at the atrial level as well. Effectiveness of catheter ablation (CA) for atrial arrhythmias (AA) in this subset of patients is currently unknown. Purpose Aim of our study is to describe acute and long-term effectiveness of CA for AA in ARVC patients. Methods Nine ARVC registries from Europe, US, and China were retrospectively searched for ARVC patients undergoing CA for AA (namely: atrial fibrillation (AF), atrial tachycardia (AT), and cavo-tricuspid dependent atrial flutter (CTI-FL)). Baseline, procedural, and long-term outcome data were collected. Results Thirty-five pts (86% male, median CHA2DS2-VASc 1 [1–2], HAS-BLED 1 [0–2], and EHRA scores 2 [2–3]) were enrolled, in which a total of 45 CA procedures for AA were performed (left atrial CA: n=19 AF, n=10 AT; right atrial CA: n=16 CTI). Mean age at AA CA was 48.2±14.8 y.o. At baseline, 63% of pts were on oral anticoagulants (OAC) (n=9 warfarin; n=13 NOAC). Catheter ablation was successful and sinus rhythm obtained at the end of the procedure in all patients, with 2 (6%) AF patients requiring electrical cardioversion. Over a median follow-up of 36 [14–74] months, 12 (27%) pts experienced arrhythmia recurrence (left atrial group: n=6 AF recurrences, n=3 AT recurrences; CTI-FL group: n=1 CTI-FL recurrence; n=1 new AF with previous CTI-dependent flutter ablation), with a 1-year follow-up resulting comparable to what has been reported in the literature for the general population. [Figure 1 and 2]. 61% pts were on OAC at last follow-up. Conclusion Age at the time of CA for AA is about 10 years younger in patients with ARVC as compared to the general population. CA for AA in ARVC pts is safe and effective; surprisingly, long-term CA outcomes for AF and left AT result comparable to those reported in the general population, whereas recurrence rates of CTI-dependent flutter seem to be higher. Funding Acknowledgement Type of funding source: None

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a leading cause of sudden cardiac death, but its diagnosis is challenging and the role of endomyocardial biopsy (EMB) is controversial and has been recently questioned. Purpose We aimed to 1) analyse the role of EMB in improving the diagnostic performance of 2010 Task Force Criteria (TFC) in the diagnosis of ARVC; 2) assess EMB safety in our population. Methods We retrospectively analysed data from 54 consecutive patients admitted to our Hospital with a clinical suspicion of ARVC undergoing endomyocardial biopsy. During hospitalization a complete assessment was performed for every patient (including electrocardiogram, echocardiogram, cardiac MRI, genetic analysis, and electroanatomic-mapping-guided endomyocardial biopsy). ARVC diagnosis was assessed for every patient using both traditional 2010 TFC and a non-invasive modified TFC (2010 TFC criteria excluding biopsy). Results Overall, 9/54 (17%) patients showed a left-dominant variant of ARVC and were therefore excluded from the analysis. Non-invasive modified TFC allowed 16/45 (36%) patients to receive a definite diagnosis; when biopsy results were added the number of definite diagnosis increased to 22/45 (49%), increasing the number of patients with a definite diagnosis by 13%. More specifically: 8/11 patients not reaching a possible diagnosis were reclassified as either possible (4/8) or borderline (4/8); 3/9 patients with a possible diagnosis were reclassified as borderline; 6/9 borderline patients received a definite diagnosis of ARVC. Globally, in 6 out of 29 patients with a non-definite diagnosis, EMB confirmed ARVC diagnosis and 17/45 (38%) patients received an upgrade in their diagnostic status with EMB. Notably, EMB also revealed the coexistence of myocarditis and fibro-fatty replacement in 5/45 (9%) patients. No patient experienced complications related to EMB. Conclusions Endomyocardial biopsy is a safe, reliable, and useful tool for ARVC diagnosis, allowing to upgrade the diagnostic status of 38% of our patients with a suspect of ARVC diagnosis. It should be performed in experienced centers and it should be guided by electro-anatomic mapping, to maximize its diagnostic power. Funding Acknowledgement Type of funding source: None

Background Current arrhythmogenic right ventricular cardiomyopathy (ARVC) diagnostic criteria are mostly based on ventricle function and dimension. Previous studies have reported a significant overlap between ARVC and chronic myocarditis, at non-invasive assessment. Purpose Tto compare biopsy-proven ARVC and myocarditis patients, in order to identify clinical, imaging and invasive electroanatomic voltage mapping (EVM) differences between the two groups. Methods Patients with borderline diagnosis of ARVC or suspected myocarditis underwent compete assessment with cardiac magnetic resonance (CMR). All patients underwent endomyocardial biopsy (EMB) with targeted tissue sampling guided by EVM. All patients with an histological diagnosis of myocarditis or ARVC were included. Results 83 patients were included, divided into 35 (42.2%) ARVC and 48 (57.8%) myocarditis. Among ARVC patients, 25 (71.4%) had right dominant ARVC, 5 (14.3%) left dominant patter and 5 (14.3%) bi-ventricular involvement. Nine patients (23.1%) with suspected clinic diagnosis of ARVC before EMB, received and histological diagnosis of myocarditis. Two (5.7%) patients with suspected myocarditis were proven to have ARVC. When comparing patients with ARVC and patients with myocarditis, univariate analysis showed that age, sex, family history, arrhythmic disorders at presentation and ECG abnormalities were similar between the two groups (P>0.05 for all the variables). There was also no significant difference with regards to bi-ventricular function and dimension at CMR evaluation. More patients with myocarditis resulted positive at late gadolinium enhancement (LGE) evaluation, although non-significantly (P=0.082). Oedema was more frequently present in patients with myocarditis (P=0.01), while adipose tissue infiltration and segmental wall motion abnormalities were more often observed in patients with ARVC (P=0.002 and P Conclusion(s) A significant number of patients who received a clinical diagnosis of Myocarditis or ARVC according to current guidelines, were subsequently reclassified after histological analysis. Patients with ARVC and myocarditis were not distinguishable on the basis of clinical features and ventricular function and dimensions. Conversely, tissue analysis with CMR demonstrated how patient with ARVC had less oedema, more adipose tissue infiltration and had more extensive scar at EVM evaluation. Funding Acknowledgement Type of funding source: None

Introduction Myocarditis is a complex inflammatory disease, usually secondary to viral infections or immune system dysregulation, with extremely heterogeneous clinical manifestations. Among them, potentially life-threatening ventricular arrhythmias (VA) may present at any stage of the disease as an expression of myocardial electrical instability. Purpose Our aim was to evaluate the efficacy of radiofrequency catheter ablation (RFCA) of VA in our large cohort of myocarditis, trying to understand the predictors of RFCA success. Methods and results 144 patients (61 men; age 43 [29–54] years) with history of myocarditis with arrhythmic presentation (118 biopsy-proven, 82%) composed our population. At presentation, 26% of patients suffered of ventricular tachycardia (VT) while in 17% cardiac arrest occurred: overall 49 patients (35%) were implanted with an ICD. The median left ventricular ejection fraction (LVEF) was 58% (48–61%). An intensive non-invasive and invasive work-up was performed: 104 patients underwent cardiac magnetic resonance (CMR) that showed late gadolinium enhancement (LGE) in 67 of them (63%). In 37 patients LGE was found in the anteroseptal portion of the left ventricle: this pattern showed association with major arrhythmic relapse (VT and ventricular fibrillation) during follow up (Fig. 1; OR 4.0, CI 95% 1.14–14.1, p=0.03). 95 patients underwent endocardial RFCA, using contact electroanatomic mapping. Interestingly, in patients with anteroseptal LGE RCFA didn't affect significantly the arrhythmic relapse (OR 5, CI 95% 0.9–33, p=0.06). Otherwise RFCA prevent arrhythmic relapse in patients that showed LGE in ventricular portion other than the anteroseptal one (OR 0.027, IC 95% 0.002–0.40, p Conclusions In myocarditis patients with VA, LGE pattern predicts arrhythmic relapse during follow-up. RFCA success rate is strictly linked to scar location, being significantly higher in patients with non-anteroseptal LGE. Figure 1 Funding Acknowledgement Type of funding source: None

Background Premature ventricular complexes (PVCs) are a common clinical problem and a critical issue with regard to sports eligibility in sportsmen. Although PVCs can be considered a benign feature of the athlete's heart adaptive phenotype, they may also be the only clinical manifestation of a concealed cardiomyopathy, potentially heralding sudden cardiac death (SCD) during sports activity. The optimal diagnostic evaluation of athletes with PVCs is currently uncertain. Purpose To evaluate the diagnostic contribution and the implications for sports eligibility assessment of a thorough non-invasive and invasive work-up including electroanatomical mapping (EAM) and endomyocardial biopsy (EMB) in athletes with PVCs. Methods We conducted a prospective, single-arm, open-label double center study. All consecutive athletes presenting for evaluation at our institution after being disqualified from participating in sports due to PVCs were included in our study. These athletes underwent a baseline non-invasive diagnostic protocol with transthoracic echocardiogram and gadolinium enhanced cardiac magnetic resonance imaging (cMRI). Subsequently, an invasive diagnostic work-up was performed, including EPS with programmed electrical stimulation, EAM and EAM-guided EMB if deemed necessary. When clinically indicated, catheter ablation was performed. Sports eligibility status was re-assessed at six months' follow-up according to Italian sports medicine guidelines. Results After diagnostic evaluation, 20 subjects out of 107 (19%) had a diagnosis of heart disease, most commonly myocarditis (n=8), arrhythmogenic right ventricular cardiomyopathy (ARVC, n=7) or dilated cardiomyopathy (DCM, n=2). On multivariate logistic-regression analysis, QRS complex/T wave abnormalities on ECG (OR 23), non left bundle branch block and inferior axis PVC morphology (OR 13), echocardiogram abnormalities (OR 24) and low-voltage areas on EAM (OR 33) were significantly associated with diagnosis of a concealed cardiac disease. Nondiagnostic abnormalities on cMRI were common in this population of athletes, prevalently involving the right ventricle. EAM-guided EMB was performed in 12 subjects (11%) and catheter ablation in 56 (52.3%). After six months, 63 athletes (59%) were judged eligible to participate in competitive sports and 23 subjects (21%) were deemed eligible to participate in non-competitive sports. Conclusions Almost one fifth of sportsmen presenting with PVCs have a concealed heart disease, most commonly myocarditis or ARVC. Non-outflow tract PVCs' morphology and abnormalities on ECG, echocardiogram and EAM are predictive of structural heart disease's detection, whereas nondiagnostic findings on cMRI can be misleading in athletes. Invasive diagnostic tests, including EAM and EAM-guided EMB, play a critical role in case of diagnostic uncertainty. More than ¾ of subjects were judged eligible to participate in sports at 6 months' follow-up. Funding Acknowledgement Type of funding source: None