Right ventricular function is a predictor for sustained ventricular tachycardia requiring anti-tachycardic pacing in arrhythmogenic ventricular cardiomyopathy: insight into transvenous vs. subcutaneous implantable cardioverter defibrillator insertion

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) patients develop ventricular arrhythmias (VAs) responsive to anti-tachycardia pacing (ATP). However, VA episodes have not been characterized in accordance with the device therapy, and with the emergence of the subcutaneous implantable cardioverter defibrillator (S-ICD), the appropriate device prescription in ARVC remains unclear. Study aim was to characterize VA events in ARVC patients during follow-up in accordance with device therapy and elicit if certain parameters are predictive of specific VA events. METHODS AND RESULTS: This was a retrospective single-centre study utilizing prospectively collated registry data of ARVC patients with ICDs. Forty-six patients were included [54.0 ± 12.1 years old and 20 (43.5%) secondary prevention devices]. During a follow-up of 12.1 ± 6.9 years, 31 (67.4%) patients had VA events [n = 2, 6.5% ventricular fibrillation (VF), n = 14], 45.2% VT falling in VF zone resulting in ICD shock(s), n = 10, 32.3% VT resulting in ATP, and n = 5, 16.1% patients had both VT resulting in ATP and ICD shock(s). Lead failure rates were high (11/46, 23.9%). ATP was successful in 34.5% of patients. Severely impaired right ventricular (RV) function was an independent predictor of VT resulting in ATP (hazard ratio 16.80, 95% confidence interval 3.74–75.2; P < 0.001) with a high predictive accuracy (area under the curve 0.88, 95%CI 0.76–1.00; P < 0.001). CONCLUSION: VA event rates are high in ARVC patients with a majority having VT falling in the VF zone resulting in ICD shock(s). S-ICDs could be of benefit in most patients with ARVC with the absence of severely impaired RV function which has the potential to avoid consequences of the high burden of lead failure

Remote Clinics and Investigations in Arrhythmia Services: What Have We Learnt During Coronavirus Disease 2019?

The coronavirus disease 2019 (COVID-19) pandemic has had a dramatic impact on the way that medical care is delivered. To minimise hospital attendance by both patients and staff, remote clinics, meetings and investigations have been used. Technologies including hand-held ECG monitoring using smartphones, patch ECG monitoring and sending out conventional Holter monitors have aided remote investigations. Platforms such as Google Meet and Zoom have allowed remote multidisciplinary meetings to be delivered effectively. The use of phone consultations has allowed outpatient care to continue despite the pandemic. The COVID-19 pandemic has resulted in a radical, and probably permanent, change in the way that outpatient care is delivered. Previous experience in remote review and the available technologies for monitoring have allowed the majority of outpatient care to be conducted without obviously compromising quality or safety

Exploiting SMART pass filter deactivation detection to minimize inappropriate subcutaneous implantable cardioverter defibrillator therapies: a real-world single-centre experience and management guide

AIMS: The SMART Pass™ (SP) algorithm is a high-pass filter that aims to reduce inappropriate therapy (IT) in subcutaneous internal cardiac defibrillator (S-ICD), but SP can deactivate due to low amplitude sensed R waves or asystole. The association between IT and SP deactivation and management strategies were evaluated, hypothesizing SP deactivation increases the risk of IT and device re-programming, or lead/generator re-positioning could reduce this risk. METHODS AND RESULTS: Retrospective single-centre audit of Emblem™ S-ICD devices implanted 2016 to 2020 utilizing health records and remote monitoring data. Cox regression models evaluated associations between SP deactivation and IT. A total of 348 patients (27 ± 16.6 months follow-up) were studied: 73% primary prevention. Thirty-eight patients (11.8%) received 83 shocks with 27 patients (7.8%) receiving a total of 44 IT. Causes of IT were oversensing (98%) and aberrantly conducted atrial fibrillation (2%). SP deactivation occurred in 32 of 348 patients (9%) and was significantly associated with increased risk of IT (hazard ratio 5.36, 95% CI 2.37-12.13). SP deactivation was due to low amplitude R waves (94%), associated with a higher defibrillation threshold at implant and presence of arrhythmogenic right ventricular cardiomyopathy. No further IT occurred 16 ± 15.5 months after corrective interventions, with changing the sensing vector being successful in 59% of cases. CONCLUSION: To reduce the risk of IT, the cause of the SP deactivation should be investigated, and appropriate reprogramming, device, or lead modifications made. Utilizing the alert for SP deactivation and electrograms could pro-actively prevent IT

Are cardiovascular risk factors also associated with the incidence of atrial fibrillation? A systematic review and field synopsis of 23 factors in 32 population-based cohorts of 20 million participants.

Established primary prevention strategies of cardiovascular diseases are based on understanding of risk factors, but whether the same risk factors are associated with atrial fibrillation (AF) remains unclear. We conducted a systematic review and field synopsis of the associations of 23 cardiovascular risk factors and incident AF, which included 84 reports based on 28 consented and four electronic health record cohorts of 20,420,175 participants and 576,602 AF events. We identified 3-19 reports per risk factor and heterogeneity in AF definition, quality of reporting, and adjustment. We extracted relative risks (RR) and 95 % confidence intervals [CI] and visualised the number of reports with inverse (RR [CI]1.00) associations. For hypertension (13/17 reports) and obesity (19/19 reports), there were direct associations with incident AF, as there are for coronary heart disease (CHD). There were inverse associations for non-White ethnicity (5/5 reports, with RR from 0.35 to 0.84 [0.82-0.85]), total cholesterol (4/13 reports from 0.76 [0.59-0.98] to 0.94 [0.90-0.97]; 8/13 reports with non-significant inverse associations), and diastolic blood pressure (2/11 reports from 0.87 [0.78-0.96] to 0.92 [0.85-0.99]; 5/11 reports with non-significant inverse associations), and direct associations for taller height (7/10 reports from 1.03 [1.02-1.05] to 1.92 [1.38-2.67]), which are in the opposite direction of known associations with CHD. A systematic evaluation of the available evidence suggests similarities as well as important differences in the risk factors for incidence of AF as compared with other cardiovascular diseases, which has implications for the primary prevention strategies for atrial fibrillation

High prevalence of bronchiectasis is linked to HTLV-1-associated inflammatory disease.

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1), a retrovirus, is the causative agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia/lymphoma (ATLL). The reported association with pulmonary disease such as bronchiectasis is less certain. METHODS: A retrospective case review of a HTLV-1 seropositive cohort attending a national referral centre. The cohort was categorised into HTLV-1 symptomatic patients (SPs) (ATLL, HAM/TSP, Strongyloidiasis and HTLV associated inflammatory disease (HAID)) and HTLV-1 asymptomatic carriers (ACs). The cohort was reviewed for diagnosis of bronchiectasis. RESULT: 34/246 ACs and 30/167 SPs had been investigated for respiratory symptoms by computer tomography (CT) with productive cough +/- recurrent chest infections the predominant indications. Bronchiectasis was diagnosed in one AC (1/246) and 13 SPs (2 HAID, 1 ATLL, 10 HAM/TSP) (13/167, RR 19.2 95 % CI 2.5-14.5, p = 0.004) with high resolution CT. In the multivariate analysis ethnicity (p = 0.02) and disease state (p < 0.001) were independent predictors for bronchiectasis. The relative risk of bronchiectasis in SPs was 19.2 (95 % CI 2.5-14.5, p = 0.004) and in HAM/TSP patients compared with all other categories 8.4 (95 % CI 2.7-26.1, p = 0.0002). Subjects not of African/Afro-Caribbean ethnicity had an increased prevalence of bronchiectasis (RR 3.45 95 % 1.2-9.7, p = 0.02). CONCLUSIONS: Bronchiectasis was common in the cohort (3.4 %). Risk factors were a prior diagnosis of HAM/TSP and ethnicity but not HTLV-1 viral load, age and gender. The spectrum of HTLV-associated disease should now include bronchiectasis and HTLV serology should be considered in patients with unexplained bronchiectasis

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation in patients with normal electrocardiograms:results from a multicentre long-term registry

AIMS : To define the clinical characteristics and long-term clinical outcomes of a large cohort of patients with idiopathic ventricular fibrillation (IVF) and normal 12-lead electrocardiograms (ECGs). METHODS AND RESULTS: Patients with ventricular fibrillation as the presenting rhythm, normal baseline, and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular conduction abnormalities, and without structural heart disease were included in a registry. A total of 245 patients (median age: 38 years; males 59%) were recruited from 25 centres. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25-110 months), 12 patients died (5%); in four of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, P = 0.001). Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.18-0.92; P = 0.03]. CONCLUSION : Patients with IVF and persistently normal ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences

A Primary Prevention Clinical Risk Score Model for Patients With Brugada Syndrome (BRUGADA-RISK).

OBJECTIVES: The goal of this study was to develop a risk score model for patients with Brugada syndrome (BrS). BACKGROUND: Risk stratification in BrS is a significant challenge due to the low event rates and conflicting evidence. METHODS: A multicenter international cohort of patients with BrS and no previous cardiac arrest was used to evaluate the role of 16 proposed clinical or electrocardiogram (ECG) markers in predicting ventricular arrhythmias (VAs)/sudden cardiac death (SCD) during follow-up. Predictive markers were incorporated into a risk score model, and this model was validated by using out-of-sample cross-validation. RESULTS: A total of 1,110 patients with BrS from 16 centers in 8 countries were included (mean age 51.8 ± 13.6 years; 71.8% male). Median follow-up was 5.33 years; 114 patients had VA/SCD (10.3%) with an annual event rate of 1.5%. Of the 16 proposed risk factors, probable arrhythmia-related syncope (hazard ratio [HR]: 3.71; p < 0.001), spontaneous type 1 ECG (HR: 3.80; p < 0.001), early repolarization (HR: 3.42; p < 0.001), and a type 1 Brugada ECG pattern in peripheral leads (HR: 2.33; p < 0.001) were associated with a higher risk of VA/SCD. A risk score model incorporating these factors revealed a sensitivity of 71.2% (95% confidence interval: 61.5% to 84.6%) and a specificity of 80.2% (95% confidence interval: 75.7% to 82.3%) in predicting VA/SCD at 5 years. Calibration plots showed a mean prediction error of 1.2%. The model was effectively validated by using out-of-sample cross-validation according to country. CONCLUSIONS: This multicenter study identified 4 risk factors for VA/SCD in a primary prevention BrS population. A risk score model was generated to quantify risk of VA/SCD in BrS and inform implantable cardioverter-defibrillator prescription

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

Dynamic monitoring in ad hoc network

This paper, present a novel model to resolve the problems of evaluating trust value of nodes, and prepare a dynamic supervising in ad hoc network as well. Trust evaluation is not only based on direct interactions among nodes, but also observing previous behaviors of nodes, which come from all interactions through the network. This model specially decreases the delay time of selecting a new head for each cluster, which leads to prepare a dynamic monitoring in intra cluster and inter cluster in ad hoc network