Adiposity and grip strength: a Mendelian randomisation study in UK Biobank.

BACKGROUND: Muscle weakness, which increases in prevalence with age, is a major public health concern. Grip strength is commonly used to identify weakness and an improved understanding of its determinants is required. We aimed to investigate if total and central adiposity are causally associated with grip strength. METHODS: Up to 470,786 UK Biobank participants, aged 38-73 years, with baseline data on four adiposity indicators (body mass index (BMI), body fat percentage (BF%), waist circumference (WC) and waist-hip-ratio (WHR)) and maximum grip strength were included. We examined sex-specific associations between each adiposity indicator and grip strength. We explored whether associations varied by age, by examining age-stratified associations (< 50 years, 50-59 years, 60-64 years,65 years +). Using Mendelian randomisation (MR), we estimated the strength of the adiposity-grip strength associations using genetic instruments for each adiposity trait as our exposure. RESULTS: In males, observed and MR associations were generally consistent: higher BMI and WC were associated with stronger grip; higher BF% and WHR were associated with weaker grip: 1-SD higher BMI was associated with 0.49 kg (95% CI: 0.45 kg, 0.53 kg) stronger grip; 1-SD higher WHR was associated with 0.45 kg (95% CI:0.41 kg, 0.48 kg) weaker grip (covariate adjusted observational analyses). Associations of BMI and WC with grip strength were weaker at older ages: in males aged < 50 years and 65 years + , 1-SD higher BMI was associated with 0.93 kg (95% CI: 0.84 kg, 1.01 kg) and 0.13 kg (95% CI: 0.05 kg, 0.21 kg) stronger grip, respectively. In females, higher BF% was associated with weaker grip and higher WC was associated with stronger grip; other associations were inconsistent. CONCLUSIONS: Using different methods to triangulate evidence, our findings suggest causal links between adiposity and grip strength. Specifically, higher BF% (in both sexes) and WHR (males only) were associated with weaker grip strength.

Identification of deliberate catheter motion at the left atrial posterior wall during pulmonary vein isolation: Validity of respiratory motion adjustment.

BACKGROUND: During automated radiofrequency (RF) annotation-guided pulmonary vein isolation (PVI), respiratory motion adjustment (RMA) is recommended, yet lacks in vivo validation. METHODS: Following contact force (CF) PVI (continuous RF, 30 W) using general anesthesia and automated RF annotation-guidance (VISITAG™: force-over-time 100% minimum 1 g; 2 mm position stability; ACCURESP™ RMA "off") in 25 patients, we retrospectively examined RMA settings "on" versus "off" at the left atrial posterior wall (LAPW). RESULTS: Respiratory motion detection occurred in eight, permitting offline retrospective comparison of RMA settings. Significant differences in LAPW RF auto-annotation occurred according to RMA setting, with curves displaying catheter position, CF and impedance data indicating "best-fit" for catheter motion detection using RMA "off." Comparing RMA "on" versus "off," respectively: total annotated sites, 82 versus 98; median RF duration per-site, 13.3 versus 10.6 s (p < 0.0001); median force time integral 177 versus 130 gs (p = 0.0002); mean inter-tag distance (ITD), 6.0 versus 4.8 mm (p = 0.002). Considering LAPW annotated site 1-to-2 transitions resulting from deliberate catheter movement, 3 concurrent with inadvertent 0 g CF demonstrated < 0.6 s difference in RF duration. However, 13 deliberate catheter movements during constant tissue contact (ITD range: 2.1-7.0 mm) demonstrated (mean) site-1 RF duration difference 3.7 s (range: -1.3 to 11.3 s): considering multiple measures of catheter position instability, the appropriate indication of deliberate catheter motion occurred with RMA "off" in all. CONCLUSIONS: ACCURESP™ respiratory motion adjustment importantly delayed the identification of deliberate and clinically relevant catheter motion during LAPW RF delivery, rendering auto-annotated RF display invalid. Operators seeking greater accuracy during auto-annotated RF delivery should avoid RMA use.

The European TeleCheck-AF project on remote app-based management of atrial fibrillation during the COVID-19 pandemic: centre and patient experiences.

AIMS: TeleCheck-AF is a multicentre international project initiated to maintain care delivery for patients with atrial fibrillation (AF) during COVID-19 through teleconsultations supported by an on-demand photoplethysmography-based heart rate and rhythm monitoring app (FibriCheck®). We describe the characteristics, inclusion rates, and experiences from participating centres according the TeleCheck-AF infrastructure as well as characteristics and experiences from recruited patients. METHODS AND RESULTS: Three surveys exploring centre characteristics (n = 25), centre experiences (n = 23), and patient experiences (n = 826) were completed. Self-reported patient characteristics were obtained from the app. Most centres were academic (64%) and specialized public cardiology/district hospitals (36%). Majority of the centres had AF outpatient clinics (64%) and only 36% had AF ablation clinics. The time required to start patient inclusion and total number of included patients in the project was comparable for centres experienced (56%) or inexperienced in mHealth use. Within 28 weeks, 1930 AF patients were recruited, mainly for remote AF control (31% of patients) and AF ablation follow-up (42%). Average inclusion rate was highest during the lockdown restrictions and reached a steady state at a lower level after easing the restrictions (188 vs. 52 weekly recruited patients). Majority (>80%) of the centres reported no problems during the implementation of the TeleCheck-AF approach. Recruited patients [median age 64 (55-71), 62% male] agreed that the FibriCheck® app was easy to use (94%). CONCLUSION: Despite different health care settings and mobile health experiences, the TeleCheck-AF approach could be set up within an extremely short time and easily used in different European centres during COVID-19.

Transmural unipolar electrogram change occurs within 7 s at the left atrial posterior wall during pulmonary vein isolation.

BACKGROUND: To assess occurrence of a histologically validated measure of transmural (TM) atrial ablation-pure R unipolar electrogram (UE) morphology change-at first-ablated left atrial posterior wall (LAPW) sites during contact force (CF)-guided pulmonary vein isolation (PVI). METHODS: Objectively annotated VISITAG™ Module and CARTOREPLAY™ (Biosense Webster Inc., Diamond Bar, CA, USA) UE morphology data were retrospectively analyzed in 23 consecutive patients undergoing PVI under general anesthesia. RESULTS: PVI without spontaneous/dormant recovery was achieved in all, employing 16.3 (3.2) min of radiofrequency (RF; 30 W) energy. All first-ablated LAPW sites demonstrated RS UE morphology preablation, with RF-induced pure R UE morphology change in 98%. Time to pure R UE morphology was significantly shorter at left-sided LAPW sites (4.9 [2.1] vs 6.7 [2.5] s; P = .02), with significantly greater impedance drop (median 13.5 vs 9.9 Ω; P = .003). Importantly, neither first-site RF duration (14.9 vs 15.0 s) nor maximum ablation catheter tip distance moved (during RF) was significantly different, yet the mean CF was significantly higher at right-sided sites (16.5 vs 11.2 g; P = .002). Concurrent impedance and objectively annotated bipolar electrogram (BE) data demonstrated ∼6-8 Ω impedance drop and ∼30% BE decrease at the time of first pure R UE morphology change. CONCLUSIONS: Using objective ablation site annotation, UE morphology evidence of TM RF effect was demonstrated far sooner than considered biologically possible according to the "conventional" 20-40 s RF per-site approach, with significantly greater ablative effect evident at left-sided sites. This novel methodology represents a scientifically more rigorous foundation toward future research into the biological effects of RF ablation in vivo.

Effect of mouthguard design on retention and potential issues arising with usability in sport.

BACKGROUND/AIMS: Mouthguard retention could potentially increase an athlete's motivation to wear the device, due to potential improvements in physical comfort. The aim of this study was to examine the retentive properties of selected customised mouthguard designs, during normal conditions (dry) and within the presence of artificial saliva (wet). Additionally, the correlation between thickness and retention was investigated. MATERIAL AND METHODS: Six different custom mouthguard designs (MG1-MG6) reported in previous studies, were pressure-formed with 2 and 4 mm blanks accordingly. Thickness was measured 10 times at seven anatomical points and the mean (±SD) was recorded. A novel rig was fabricated to connect the mouthguards to a Hounsfield H10KS Tensometer, which was used to fully displace each device from the model at a constant rate of 50 mm/min. The test was repeated under both dry and wet conditions. RESULTS: Retention forces recorded at the anterior region demonstrated higher measurements under wet conditions than dry (P < 0.001). The total retention of the mouthguards was influenced by alterations in their design. Trend analysis indicated that 64% of MG retention could be explained by their thickness under dry conditions and 55% when wet. CONCLUSIONS: Design and thickness of mouthguards are key factors in retention. Mouthguard fabrication techniques should be considered in order to minimize dislodgment of the devices as well as potentially increasing the wearability of mouthguards during sport.

The Effect of Atrial Fibrillation Ablation Techniques on P Wave Duration and P Wave Dispersion.

BACKGROUND: A reduction in surface electrocardiogram (ECG) P wave duration and dispersion is associated with improved outcomes in atrial fibrillation ablation. We investigated the effects of different ablation strategies on P wave duration and dispersion, hypothesising that extensive left atrial (LA) ablation with left atrial posterior wall isolation would give a greater reduction in P wave duration than more limited ablation techniques. METHODS: A retrospective analysis of ECGs from patients who have undergone atrial fibrillation (AF) ablation was performed and pre-procedural sinus rhythm ECGs were compared with the post procedure ECGs. Maximal P wave duration was measured in leads I or II, minimum P wave duration in any lead and values were calculated for P wave duration and dispersion. Left atrial dimensions and medications at the time of ECG were documented. Ablation strategies compared were; pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF) and the persistent AF (PsAF) ablation strategies of pulmonary vein isolation plus additional linear lesions (Lines), left atrial posterior wall isolation via catheter (PWI) and left atrial posterior wall isolation via staged surgical and catheter ablation (Hybrid). RESULTS: Sixty-nine patients' ECGs were analysed: 19 PVI, 21 Lines, 14 PWI, 15 Hybrid. Little correlation was seen between pre-procedure left atrial size and P wave duration (r=0.24) but LA size and P wave duration was larger in PsAF patients. A significant difference was seen in P wave reduction driven by Hybrid AF ablation (p<0.005) and Lines (<0.02). There was no difference amongst P wave dispersion between groups but the largest reduction was seen in the Hybrid ablation group. CONCLUSIONS: P wave duration increased with duration of continuous atrial fibrillation. Hybrid AF ablation significantly reduced P wave duration and dispersion compared to other ablation strategies including posterior wall isolation via catheter despite this being the same lesion set.

A novel approach to mapping the atrial ganglionated plexus network by generating a distribution probability atlas.

INTRODUCTION: The ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system are implicated in arrhythmogenesis. GP localization by stimulation of the epicardial fat pads to produce atrioventricular dissociating (AVD) effects is well described. We determined the anatomical distribution of the left atrial GPs that influence atrioventricular (AV) dissociation. METHODS AND RESULTS: High frequency stimulation was delivered through a Smart-Touch catheter in the left atrium of patients undergoing atrial fibrillation (AF) ablation. Three dimensional locations of points tested throughout the entire chamber were recorded on the CARTO™ system. Impact on the AV conduction was categorized as ventricular asystole, bradycardia, or no effect. CARTO maps were exported, registered, and transformed onto a reference left atrial geometry using a custom software, enabling data from multiple patients to be overlaid. In 28 patients, 2108 locations were tested and 283 sites (13%) demonstrated (AVD-GP) effects. There were 10 AVD-GPs (interquartile range, 11.5) per patient. Eighty percent (226) produced asystole and 20% (57) showed bradycardia. The distribution of the two groups was very similar. Highest probability of AVD-GPs (>20%) was identified in: inferoseptal portion (41%) and right inferior pulmonary vein base (30%) of the posterior wall, right superior pulmonary vein antrum (31%). CONCLUSION: It is feasible to map the entire left atrium for AVD-GPs before AF ablation. Aggregated data from multiple patients, producing a distribution probability atlas of AVD-GPs, identified three regions with a higher likelihood for finding AVD-GPs and these matched the histological descriptions. This approach could be used to better characterize the autonomic network.

Impact of Above-Average Proanabolic Nutrients Is Overridden by High Protein and Energy Intake in the Muscle-Tendon Unit Characteristics of Middle- to Older-Aged Adults.

Background: The impact, within a single cohort, of independent modulators of skeletal muscle quality, including age, adiposity and obesity, habitual nutritional intake, and physical activity (PA), is unclear. Objective: We examined the bivariate associations between age, adiposity, habitual nutritional intake, and PA against 11 key intrinsic muscle-tendon unit (MTU) characteristics to identify the strongest predictors. We also compared overall profile differences between MTU categories with the use of z scores shown in radar graphs. Methods: Fifty untrained independently living men (n = 15) and women (n = 35) aged 43-80 y (mean ± SD: 64 ±9 y) were categorized by adiposity [men: normal adiposity (NA) <28%, high adiposity (HA) ≥28%; women: NA <40%, HA ≥40%] and body mass index [BMI (in kg/m2); normal: 18 to <25; overweight: ≥25 to <30; and obese: ≥30]. Group differences were examined by body composition assessed with the use of dual-energy X-ray absorptiometry, habitual nutritional intake through a 3-d food diary, PA (work, leisure, sport) using the Baecke questionnaire, 14 serum cytokine concentrations using multiplex luminometry, and 11 MTU characteristics of the gastrocnemius medialis using a combination of isokinetic dynamometry, electromyography, and ultrasonography. Results: Interestingly, classification by BMI highlighted differences between normal and obese individuals in 6 of 11 MTU characteristics (P < 0.001 to P = 0.043). No significant differences were reported in serum cytokine concentrations between adiposity and BMI classifications. BMI predicted 8 of 11 (r = 0.62-0.31, P < 0.001 to P = 0.032), daily energy intake predicted 7 of 11 (r = 0.45-0.34, P = 0.002-0.036), age predicted 5 of 11 (r = -0.49-0.32, P < 0.001 to P = 0.032), work-based PA predicted 5 of 11 (r = 0.43-0.32, P = 0.003-0.048), and adiposity predicted 4 of 11 (r = 0.51-0.33, P < 0.001 to P = 0.022) MTU characteristics. Mathematical z scores and radar graphs showed how endocrine and dietary profiles, but not PA, differed between the top and bottom ∼20% of muscle unit size and specific force. Conclusions: Given the number of factors associated with MTU, education should be targeted to both adequate food quantity and quality (especially protein intake) and increasing habitual moderate to vigorous PA while decreasing sedentary behavior. Specific endocrine variables are also proposed as key pharmaceutical targets.

A new approach for second-order perturbation theory.

A new second-order perturbation theory (MP2) approach is presented for closed shell energy evaluations. The new algorithm has a significantly lower memory footprint, a lower FLOP (floating point operations) count, and a lower time to solution compared to previously implemented parallel MP2 methods in the GAMESS software package. Additionally, this algorithm features an adaptive approach for the disk/distributed memory storage of the MP2 amplitudes. The algorithm works well on a single workstation, small cluster, and large Cray cluster, and it allows one to perform large calculations with thousands of basis functions in a matter of hours on a single workstation. The same algorithm has been adapted for graphical processing unit (GPU) architecture. The performance of the new GPU algorithm is also discussed.

Xylazine Use Among People Who Inject Drugs, Philadelphia 2022.

OBJECTIVES: Xylazine is commonly mixed with illicit opioids in Philadelphia, and potential associations with wound issues, infectious diseases, and overdoses are of public health concern. We used data from the National HIV Behavioral Surveillance Survey among persons who inject drugs (PWIDs) in Philadelphia to better identify individuals at risk and inform patients and clinicians about xylazine risk factors. METHODS: We compared characteristics of participants who reported using xylazine to those who reported not using xylazine in the past 12 months. Among those who reported xylazine use, we compared characteristics between people who prefer and did not prefer to use xylazine. RESULTS: In this sample of PWIDs, most prefer not to use xylazine, yet use is common. Compared with PWIDs not using xylazine, PWIDs who use xylazine were more likely to have recent homelessness, polysubstance use, overdose history, and hepatitis C virus infection ( P < 0.05 for all comparisons). Compared with concordant xylazine use, discordant xylazine use was associated with lower preference for fentanyl, heroin as the primary injection drug, and lower use of syringe service programs ( P < 0.05 for all comparisons). CONCLUSIONS: Public health entities should prioritize studying the use and health effects of xylazine in their jurisdictions and consider supporting point-of-care and drug-checking surveillance in addition to raising awareness of xylazine in the drug supply.

Glucose neurotoxicity.

Neurons have a constantly high glucose demand, and unlike muscle cells they cannot accommodate episodic glucose uptake under the influence of insulin. Neuronal glucose uptake depends on the extracellular concentration of glucose, and cellular damage can ensue after persistent episodes of hyperglycaemia--a phenomenon referred to as glucose neurotoxicity. This article reviews the pathophysiological manifestation of raised glucose in neurons and how this can explain the major components of diabetic neuropathy.

Absolute risk reduction in total mortality with implantable cardioverter defibrillators: analysis of primary and secondary prevention trial data to aid risk/benefit analysis.

AIMS: Absolute risk reduction (ARR) and number needed to treat (NNT) are considered by many to be the most appropriate figures to use for the informed consent process, yet the results of published implantable cardioverter defibrillators (ICD) trials are frequently presented as relative risk reduction or odds ratio. The period over which risk reduction is calculated also varies between trials, making comparison difficult. METHODS AND RESULTS: Published ICD trials used to formulate national and international guidelines were examined for 1, 2, and 3 year total mortality in ICD and medically treated patients. The number of patients enrolled and at risk at these time points were also sought. Where the raw data were not included in the original text, estimates were taken from published Kaplan-Meier graphs. Eight primary prevention (PP) trials, three secondary prevention (SP) trials, and one SP meta-analyses were included. For PP, ARR at 3-year follow-up ranged from 0 (no benefit) to 24.6% (NNT = 4). For SP, ARR at 3-year follow up ranged from 3.7% (NNT = 27) to 11.3% (NNT = 9). Absolute risk reduction increased with follow-up in PP trials, whereas there was considerable variation in SP trials. Overall, very few trial patients received 3-year follow-up, giving wide confidence intervals (CIs). CONCLUSION: Absolute risk reduction from ICD trials varies significantly depending upon trial entry criteria, subgroup characteristics, and duration of follow-up. The relatively small number of patients followed for 2 or more years leads to wide CIs. Despite these limitations, the standardized ARR and NNT data presented may give a more individualized estimate of risk/benefit that could potentially aid an informed consent process.

Transseptal left ventricular lead placement using snare technique.

BACKGROUND: Coronary sinus (CS) lead placement for cardiac resynchronization therapy has a failure rate of ∼5-10%. Here we describe a way of implanting an endocardial left ventricular (LV) lead via a transseptal puncture (TSP), using a GooseNeck snare and active fixation lead. METHODS: Three male patients (67-83 years) with failed or extracted epicardial LV leads implanted via the CS had an endocardial LV lead implanted. TSP was performed via a femoral vein. The active fixation pacing lead was advanced to the right atrium from a subclavian vein. A GooseNeck snare was passed via the TSP sheath and used to grasp the tip of the pacing lead. The sheath, GooseNeck snare, and pacing lead tip were then passed to the left atrium by sliding the system up the TSP guidewire and across the interatrial septum before deflecting the lead to permit implantation in the left ventricle. RESULTS: Successful implantation was performed in all patients with an LV implant time of 25-55 minutes. CONCLUSION: The use of a GooseNeck snare via a deflectable transseptal sheath represents a reliable alternative method for endocardial LV lead placement in patients with failed CS LV lead implantation.

Lifetime body mass index and grip strength at age 46 years: the 1970 British Cohort Study.

BACKGROUND: Ongoing rises in obesity prevalence have prompted growing concerns about potential increases in the burden of age-related musculoskeletal conditions including sarcopenia and sarcopenic obesity. This is of particular concern for future generations of older adults who have lived more of their lives in an obesogenic environment than current generations of older adults. We aimed to study longitudinal associations between body mass index (BMI) and grip strength in midlife using data from a large population-based sample, the 1970 British Cohort Study (BCS70). METHODS: BCS70 participants with valid measures of maximum grip strength at age 46 years were included in analyses [3671 males (49%) and 3876 females (51%)]. Using sex-specific linear regression models, we examined associations of (i) BMI at ages 10, 16, 30, and 46 years; (ii) body fat percentage (BF%) and waist-hip ratio at age 46 years; (iii) BMI gains between 10-16, 16-30, and 30-46; and (iv) age at onset of obesity, with grip strength. RESULTS: At age 46 years, mean (standard deviation) grip strength was 48.10 kg (8.98) in males and 29.61 kg (5.81) in females. Higher BMI at all ages was associated with stronger grip, and the scale of associations was greater in males than females from age 16 onwards (Psex interactions  < 0.01). For example, in fully adjusted models, a 1 standard deviation increase in BMI at age 16 was associated with mean differences in grip strength at age 46 years of 1.41 kg (95% confidence interval: 1.07, 1.75) in males and 0.72 kg (0.53, 0.91) in females. Higher BF% at age 46 was also associated with stronger grip in both sexes. Greater gains in BMI between ages 10 and 16 were associated with stronger grip in both sexes, but subsequent gains in BMI were only associated with stronger grip in males. Associations of greater length of exposure to obesity and stronger grip were also more consistent among males than females. For example, in fully adjusted models, mean grip strength at age 46 years of males and females who had been obese since age 10 or 16 years was 4.39 kg (1.85, 6.93) and 1.25 kg (-0.18, 2.69) higher than males and females who had never been obese, respectively. CONCLUSIONS: Higher BMI from childhood onwards is associated with stronger grip at age 46 years. This suggests that, at this age, anabolic effects of fat on muscle are outweighing the catabolic effects thought to lead to the manifestation of sarcopenic obesity later in life, especially among men. Midlife may be an optimal time to intervene to prevent sarcopenic obesity.

Aerobic capacity and skeletal muscle characteristics in glycogen storage disease IIIa: an observational study.

BACKGROUND: Individuals with glycogen storage disease IIIa (GSD IIIa) (OMIM #232400) experience muscle weakness and exercise limitation that worsen through adulthood. However, normative data for markers of physical capacity, such as strength and cardiovascular fitness, are limited. Furthermore, the impact of the disease on muscle size and quality is unstudied in weight bearing skeletal muscle, a key predictor of physical function. We aim to produce normative reference values of aerobic capacity and strength in individuals with GSD IIIa, and to investigate the role of muscle size and quality on exercise impairment. RESULTS: Peak oxygen uptake (V̇O2peak) was lower in the individuals with GSD IIIa than predicted based on demographic data (17.0 (9.0) ml/kg/min, 53 (24)% of predicted, p = 0.001). Knee extension maximum voluntary contraction (MVC) was also substantially lower than age matched predicted values (MVC: 146 (116) Nm, 57% predicted, p = 0.045), though no difference was found in MVC relative to body mass (1.88 (2.74) Nm/kg, 61% of predicted, p = 0.263). There was a strong association between aerobic capacity and maximal leg strength (r = 0.920; p = 0.003). Substantial inter-individual variation was present, with a high physical capacity group that had normal leg strength (MVC), and relatively high V̇O2peak, and a low physical capacity that display impaired strength and substantially lower V̇O2peak. The higher physical capacity sub-group were younger, had larger Vastus Lateralis (VL) muscles, greater muscle quality, undertook more physical activity (PA), and reported higher health-related quality of life. CONCLUSIONS: V̇O2peak and knee extension strength are lower in individuals with GSD IIIa than predicted based on their demographic data. Patients with higher physical capacity have superior muscle size and structure characteristics and higher health-related quality of life, than those with lower physical capacity. This study provides normative values of these important markers of physical capacity.

Hunting for the cause: Evidence for prion-like mechanisms in Huntington's disease.

The hypothesis that pathogenic protein aggregates associated with neurodegenerative diseases spread from cell-to-cell in the brain in a manner akin to infectious prions has gained substantial momentum due to an explosion of research in the past 10-15 years. Here, we review current evidence supporting the existence of prion-like mechanisms in Huntington's disease (HD), an autosomal dominant neurodegenerative disease caused by expansion of a CAG repeat tract in exon 1 of the huntingtin (HTT) gene. We summarize information gained from human studies and in vivo and in vitro models of HD that strongly support prion-like features of the mutant HTT (mHTT) protein, including potential involvement of molecular features of mHTT seeds, synaptic structures and connectivity, endocytic and exocytic mechanisms, tunneling nanotubes, and nonneuronal cells in mHTT propagation in the brain. We discuss mechanisms by which mHTT aggregate spreading and neurotoxicity could be causally linked and the potential benefits of targeting prion-like mechanisms in the search for new disease-modifying therapies for HD and other fatal neurodegenerative diseases.

Rationale and study design of the MINERVA study: Multicentre Investigation of Novel Electrocardiogram Risk markers in Ventricular Arrhythmia prediction-UK multicentre collaboration.

INTRODUCTION: The purpose of this study is to assess the ability of two new ECG markers (Regional Repolarisation Instability Index (R2I2) and Peak Electrical Restitution Slope) to predict sudden cardiac death (SCD) or ventricular arrhythmia (VA) events in patients with ischaemic cardiomyopathy undergoing implantation of an implantable cardioverter defibrillator for primary prevention indication. METHODS AND ANALYSIS: Multicentre Investigation of Novel Electrocardiogram Risk markers in Ventricular Arrhythmia prediction is a prospective, open label, single blinded, multicentre observational study to establish the efficacy of two ECG biomarkers in predicting VA risk. 440 participants with ischaemic cardiomyopathy undergoing routine first time implantable cardioverter-defibrillator (ICD) implantation for primary prevention indication are currently being recruited. An electrophysiological (EP) study is performed using a non-invasive programmed electrical stimulation protocol via the implanted device. All participants will undergo the EP study hence no randomisation is required. Participants will be followed up over a minimum of 18 months and up to 3 years. The first patient was recruited in August 2016 and the study will be completed at the final participant follow-up visit. The primary endpoint is ventricular fibrillation or sustained ventricular tachycardia >200 beats/min as recorded by the ICD. The secondary endpoint is SCD. Analysis of the ECG data obtained during the EP study will be performed by the core lab where blinding of patient health status and endpoints will be maintained. ETHICS AND DISSEMINATION: Ethical approval has been granted by Research Ethics Committees Northern Ireland (reference no. 16/NI/0069). The results will inform the design of a definitive Randomised Controlled Trial (RCT). Dissemination will include peer reviewed journal articles reporting the qualitative and quantitative results, as well as presentations at conferences and lay summaries. TRIAL REGISTRATION NUMBER: NCT03022487.

Ectopy-triggering ganglionated plexuses ablation to prevent atrial fibrillation: GANGLIA-AF study.

BACKGROUND: The ganglionated plexuses (GPs) of the intrinsic cardiac autonomic system may play a role in atrial fibrillation (AF). OBJECTIVE: We hypothesized that ablating the ectopy-triggering GPs (ET-GPs) prevents AF. METHODS: GANGLIA-AF (ClinicalTrials.gov identifier NCT02487654) was a prospective, randomized, controlled, 3-center trial. ET-GPs were mapped using high frequency stimulation, delivered within the atrial refractory period and ablated until nonfunctional. If triggered AF became incessant, atrioventricular dissociating GPs were ablated. We compared GP ablation (GPA) without pulmonary vein isolation (PVI) against PVI in patients with paroxysmal AF. Follow-up was for 12 months including 3-monthly 48-hour Holter monitors. The primary end point was documented ≥30 seconds of atrial arrhythmia after a 3-month blanking period. RESULTS: A total of 102 randomized patients were analyzed on a per-protocol basis after GPA (n = 52; 51%) or PVI (n = 50; 49%). Patients who underwent GPA had 89 ± 26 high frequency stimulation sites tested, identifying a median of 18.5% (interquartile range 16%-21%) of GPs. The radiofrequency ablation time was 22.9 ± 9.8 minutes in GPA and 38 ± 14.4 minutes in PVI (P < .0001). The freedom from ≥30 seconds of atrial arrhythmia at 12-month follow-up was 50% (26 of 52) with GPA vs 64% (32 of 50) with PVI (log-rank, P = .09). ET-GPA without atrioventricular dissociating GPA achieved 58% (22 of 38) freedom from the primary end point. There was a significantly higher reduction in antiarrhythmic drug usage postablation after GPA than after PVI (55.5% vs 36%; P = .05). Patients were referred for redo ablation procedures in 31% (16 of 52) after GPA and 24% (12 of 50) after PVI (P = .53). CONCLUSION: GPA did not prevent atrial arrhythmias more than PVI. However, less radiofrequency ablation was delivered to achieve a higher reduction in antiarrhythmic drug usage with GPA than with PVI.

ICD lead implantation following sharp cannulation of a blocked superior vena cava.

Blocked superior vena cava (SVC) presents a well-recognized problem for the implantation of device leads. Implantable cardioverter defibrillator (ICD) leads pose a greater challenge than the pacing leads by requiring an adequate shock vector for successful defibrillation. We present here a novel technique of opening the blocked SVC to facilitate ICD lead implantation through the upper venous system.