Transient complete heart block following catheter ablation of a left lateral accessory pathway.

A 16-year-old female with symptomatic Wolff-Parkinson-White (WPW) syndrome underwent catheter ablation of a left-sided lateral accessory pathway. The accessory pathway was eliminated with the first ablation lesion; however, the patient immediately developed complete heart block (CHB). At first, complete heart block was thought to be due to ablation of left atrial extension of the AV node, and pacemaker therapy was considered. However, careful ECG analysis revealed that the development of CHB was in fact due to bump injury to the AV node during transseptal catheterization. Conservative management allowed resolution of AV nodal conduction without need for a permanent pacemaker

943-14 Termination and Suppression of Experimental Atrial Flutter by Quinidine: Effects on Dispersion of Repolarization and Conduction

Recent studies in our canine crush-injury (CI) model of atrial flutter (AFL) suggest that elimination of dispersion of repolarization is an important antiarrhythmic effect of newer class 3 antiarrhythmic drugs. However, the effects of class 1a antiarrhythmic drugs on dispersion of repolarization and its relation to termination and suppression of AFL have not been studied. Therefore, the effects of quinidine 10) were studied in 8 dogs, using a 56-electrode plaque placed over the CI to map activation patterns during AFL and its induction and termination, and to measure effective refractory periods (ERP) at all 56 electrodes and conduction velocity (CV) parallel to the CI, before and after 0 (10mg/kg over 10 min, then 3 mg/kg/hr).ResultsInduction of AFL at baseline was due to unidirectional block below the CI. a terminated AFL in only 3 dogs, due to conduction block below the CI, occurring either abruptly or following premature eccentric activation of the reentry circuit. Sustained AFL was reinducible after a in 5 dogs, and nonsustained AFL in 3. Mean overall ERP increased 14% from 112±11msec at baseline to 128±15msec after a (p<0.001). ERP was longer below CI than above (115±10ms vs 109±10ms, p<0.001). and this difference was not eliminated by a (133±14ms vs 123±14ms, p<0.001). Overall dispersion of ERP (9.9±2.3msec) was unchanged by a (1 0.0±1.3msec, p=NS). The number of adjacent electrodes with ERP difference ≥20msec (14.4±10.4) was also not changed by a (12.5±7.9, P = NS). CV was slower below the CI than above at baseline (0.7±0.1 vs 0.9±0.1 mis,p<0.001), and this difference was unchanged by a (0.6±0.1 vs 0.8±0.1 mis,p<0.001). although CV was slowed overall(p<0.01). a prolonged AFL cycle length 57% from 123±12 to 198±37msec (p<0.01).Conclusion1) Baseline dispersion of ERP and CV is important for initiating and sustaining AFL in this model. 2) The class 1a drug quinidine is relatively ineffective in terminating and suppressing AFL in this model, because it prolongs ERP less than AFL cycle length and it does not eliminate dispersion of ERP or C

Ventricular Arrhythmia Discriminator Programming and the Impact on the Incidence of Inappropriate Therapy in Patients with Implantable Cardiac Defibrillators

Background: The incidence of inappropriate therapy from implantable cardioverter defibrillators (ICDs) has been reduced by programming ventricular arrhythmia discriminators (VAD) on at the time of implant. Objective: To determine which VAD is most effective in preventing inappropriate therapy.Methods and Results: Dual chamber ICD (n=48) or cardiac resynchronization therapy defibrillator (CRT-D) (n=55) implantation was performed in 103 patients (M=94, F=9). Patients were followed prospectively for therapy events (shock or anti-tachycardia pacing) for a mean 362±289 days. Events were correlated with clinical characteristics and VAD programming. Of the 103 pts followed, 11 received inappropriate therapy (IT), 15 received appropriate therapy (AT), and 77 received no therapy (NT). In the AT and IT groups, a total of 207 events (ATP=171, shock=36) were observed. A total of sixty-four electrograms (EGMs) were analyzed. Programming VADs "ON" versus "OFF" reduced the incidence of IT events compared to those receiving AT or NT events (p<.01), with a trend in fewer patients receiving IT (31.3% "ON" vs 55.6% "OFF", p = 0.131). Programming atrial fibrillation (AF) detection ON resulted in fewer patients receiving IT compared to those receiving AT or NT (3.6% vs 19%, p<.05). Furthermore, programming AF or AFL algorithms "ON", resulted in overall fewer episodes of IT therapy (p<.01). Conclusions: AF or AFL discriminators significantly reduced the incidence of IT, and were predominantly responsible for the benefits from VAD programming observed in this study. Activating these features as part of routine ICD or CRT-D programming may provide a simple and effective alternative to the use of more complex and multiple VAD strategies

Anatomy-Based Algorithms for Detecting Oral Cancer Using Reflectance and Fluorescence Spectroscopy

OBJECTIVES: We used reflectance and fluorescence spectroscopy to noninvasively and quantitatively distinguish benign from dysplastic/malignant oral lesions. We designed diagnostic algorithms to account for differences in the spectral properties among anatomic sites (gingiva, buccal mucosa, etc). METHODS: In vivo reflectance and fluorescence spectra were collected from 71 patients with oral lesions. The tissue was then biopsied and the specimen evaluated by histopathology. Quantitative parameters related to tissue morphology and biochemistry were extracted from the spectra. Diagnostic algorithms specific for combinations of sites with similar spectral properties were developed. RESULTS: Discrimination of benign from dysplastic/malignant lesions was most successful when algorithms were designed for individual sites (area under the receiver operator characteristic curve [ROC-AUC],0.75 for the lateral surface of the tongue) and was least accurate when all sites were combined (ROC-AUC, 0.60). The combination of sites with similar spectral properties (floor of mouth and lateral surface of the tongue) yielded an ROC-AUC of 0.71. CONCLUSIONS: Accurate spectroscopic detection of oral disease must account for spectral variations among anatomic sites. Anatomy-based algorithms for single sites or combinations of sites demonstrated good diagnostic performance in distinguishing benign lesions from dysplastic/malignant lesions and consistently performed better than algorithms developed for all sites combined.National Institutes of Health (U.S) (R0I-CA097966)National Institutes of Health (U.S) (P4I-RR02594- 21

Prioritization of HCV treatment in the direct-acting antiviral era: an economic evaluation

BACKGROUND & AIMS: We determined the optimal HCV treatment prioritization strategy for interferon-free (IFN-free) HCV direct-acting antivirals (DAAs) by disease stage and risk status incorporating treatment of people who inject drugs (PWID). METHODS: A dynamic HCV transmission and progression model compared the cost-effectiveness of treating patients early vs. delaying until cirrhosis for patients with mild or moderate fibrosis, where PWID chronic HCV prevalence was 20, 40 or 60%. Treatment duration was 12weeks at £3300/wk, to achieve a 95% sustained viral response and was varied by genotype/stage in alternative scenarios. We estimated long-term health costs (in £UK=€1.3=$1.5) and outcomes as quality adjusted life-years (QALYs) gained using a £20,000 willingness to pay per QALY threshold. We ranked strategies with net monetary benefit (NMB); negative NMB implies delay treatment. RESULTS: The most cost-effective group to treat were PWID with moderate fibrosis (mean NMB per early treatment £60,640/£23,968 at 20/40% chronic prevalence, respectively), followed by PWID with mild fibrosis (NMB £59,258 and £19,421, respectively) then ex-PWID/non-PWID with moderate fibrosis (NMB £9,404). Treatment of ex-PWID/non-PWID with mild fibrosis could be delayed (NMB -£3,650). In populations with 60% chronic HCV among PWID it was only cost-effective to prioritize DAAs to ex-PWID/non-PWID with moderate fibrosis. For every one PWID in the 20% chronic HCV setting, 2 new HCV infections were averted. One extra HCV-related death was averted per 13 people with moderate disease treated. Rankings were unchanged with reduced drug costs or varied sustained virological response/duration by genotype/fibrosis stage. CONCLUSIONS: Treating PWID with moderate or mild HCV with IFN-free DAAs is cost-effective compared to delay until cirrhosis, except when chronic HCV prevalence and reinfection risk is very high

Hepatitis C virus transmission between eight high-income countries among men who have sex with men: a whole-genome analysis.

BACKGROUND Microelimination of the hepatitis C virus (HCV) among men who have sex with men (MSM) could be complicated by continuous external introductions and the emergence of phylogenetic clusters harbouring clinically significant resistance-associated substitutions (RAS). To investigate international clustering and the prevalence and transmission of RAS, we aimed to analyse whole-genome HCV sequences from MSM with a recently acquired infection who participated in a large, international HCV treatment trial. METHODS For this whole-genome analysis, we obtained HCV sequences from 128 MSM who had acquired HCV within the past 12 months and were participating in the REACT trial. The participants from whom sequences were obtained were recruited at 24 sites in eight countries. We inferred maximum-likelihood phylogenies and identified transmission clusters for HCV genotypes separately. We constructed time-scaled phylogenies to estimate cluster introduction dates and used a Bayesian Skygrid approach to estimate the effective population size over the past 50 years. We calculated the prevalence of RAS and the extent of RAS transmission in the study population. FINDINGS The majority of recent HCV infections were part of international networks that arose in the late 1990s and early 2000s. Sequences obtained in the same country clustered frequently, and in 36% of subclusters since 2015 we found evidence of international transmission. European MSM were more likely than non-European MSM to be in a cluster (odds ratio 11·9 [95% CI 3·6-43·4], p<0·0001). The effective population size decreased rapidly since around 2015 in Europe. RAS associated with substantially diminished cure rates were infrequently detected and transmission of highly resistant viruses was not observed. INTERPRETATION Despite antiviral treatment becoming widely available, international transmission of HCV among MSM has still occurred over the past 8 years, which could complicate microelimination of the virus in this population. RAS-enriched clusters and widespread RAS transmission are currently not a threat to elimination goals. These findings support an international approach for HCV microelimination among MSM. FUNDING National Institutes of Health and Dr. C.J. Vaillant Fonds

Sexual and drug use risk behaviour trajectories among people treated for recent HCV infection: the REACT study.

INTRODUCTION Exploration of sexual and drug use behaviours following treatment for recent hepatitis C virus (HCV) is limited. This analysis modelled behavioural trajectories following treatment for recent HCV and assessed reinfection. METHODS Participants treated for recent HCV in an international trial (enrolled 2017-2019) were followed at 3-monthly intervals for up to 2 years to assess longitudinal behaviours. Population-averaged changes were assessed using generalized estimating equations. Distinct behavioural trajectories were identified using group-based trajectory modelling. HCV reinfection incidence was calculated using person-years (PY) of observation. RESULTS During the follow-up of 212 participants (84% gay and bisexual men [GBM]; 69% HIV; 26% current injecting drug use [IDU]), behavioural trajectories for IDU and stimulant use (past month) did not change. However, population-averaged decreases in the likelihood of daily IDU (adjusted odds ratio [AOR] 0.83; 95% CI 0.72, 0.95) and opioid use (AOR 0.84; 95% CI 0.75, 0.93) were observed. Among GBM, behavioural trajectories for chemsex did not change. Population-averaged decreases in condomless anal intercourse with casual male partners (CAI-CMP) (AOR 0.95; 95% CI 0.90, 0.99) and group-sex (AOR 0.86; 95% CI 0.80, 0.93) were observed, but masked distinct trajectories. While a proportion had a decreased probability of CAI-CMP (23%) and group-sex (59%) post-treatment, a substantial proportion retained a high probability of these behaviours. High HCV reinfection incidence was observed for the sustained high probability IDU (33.0/100 PY; 95% CI 17.7, 61.3) and chemsex (23.3/100 PY; 95% CI 14.5, 37.5) trajectories. CONCLUSIONS Limited sexual and drug use behavioural change was observed following treatment for recent HCV, supporting access to surveillance and (re)treatment