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BACKGROUND: Reported cases of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are increasing among Canadian men. Estimates of community-based CT/NG prevalence are lacking among gay, bisexual and other men who have sex with men (GBM). METHODS: Respondent driven sampling was used to recruit GBM in Montreal, Canada between February 2017 and June 2018. Specimens provided from urogenital, rectal and pharyngeal sites were analyzed using nucleic acid amplification test (NAAT) to detect CT/NG. Prevalence estimates of CT/NG, overall and by anatomical site were calculated. All estimates are RDS-adjusted. RESULTS: Among 1177 GBM, the prevalence of rectal, urogenital, pharyngeal and overall were respectively 2.4%, 0.4%, 0.4% and 2.8% for CT infections, and 3.1%, 0.4%, 3.5% and 5.6% for NG infections. If testing had been limited to the urogenital site, 80% and 94% of CT and NG infections, respectively, would have been missed. CONCLUSIONS: This community-based study among GBM shows that the CT prevalence was about half of that observed for NG. A large part of CT/NG infections involves only the extragenital sites, highlighting the need for systematic multisite screening regardless of symptoms. In the mist of the COVID-19 pandemic and the limited CT/NG screening capacity due to test kits shortage, it might be considered to prioritize rectal and pharyngeal CT/NG testing over urogenital testing in asymptomatic GBM.

Background: In Canada, gay, bisexual and other men who have sex with men (GBM) are disproportionately affected by HIV. Our objective was to describe access to HIV pre-exposure prophylaxis (PrEP) and identify factors associated with not using PrEP among self-reported HIV-negative or HIV-unknown GBM. Methods: This was a cross-sectional analysis of the Engage study cohort. Between 2017 and 2019, sexually active GBM aged 16 years or more in Montréal, Toronto and Vancouver were recruited via respondent-driven sampling (RDS). Participation included testing for HIV and sexually transmitted and blood-borne infections, and completion of a questionnaire. We examined PrEP access using a health care services model and fit RDS-adjusted logistic regressions to determine correlates of not using PrEP among those for whom PrEP was clinically recommended and who were aware of the intervention. Results: A total of 2449 GBM were recruited, of whom 2008 were HIV-negative or HIV-unknown; 1159 (511 in Montréal, 247 in Toronto and 401 in Vancouver) met clinical recommendations for PrEP. Of the 1159, 1100 were aware of PrEP (RDS-adjusted proportion: Montréal 84.6%, Toronto 94.2%, Vancouver 92.7%), 678 had felt the need for PrEP in the previous 6 months (RDS-adjusted proportion: Montréal 39.2%, Toronto 56.1%, Vancouver 49.0%), 406 had tried to access PrEP in the previous 6 months (RDS-adjusted proportion: Montréal 20.6%, Toronto 33.2%, Vancouver 29.6%) and 319 had used PrEP in the previous 6 months (RDS-adjusted proportion: Montréal 14.5%, Toronto 21.6%, Vancouver 21.8%). Not using PrEP was associated with several factors, including not feeling at high enough risk, viewing PrEP as not completely effective, not having a primary care provider and lacking medication insurance. Interpretation: Although half of GBM met clinical recommendations for PrEP, less than a quarter of them reported use. Despite high levels of awareness, a programmatic response that addresses PrEP-related perceptions and health care system barriers is needed to scale up PrEP access among GBM in Canada.

Pre-exposure prophylaxis (PrEP) became publicly available in Quebec for gay, bisexual and other men who have sex with men (GBM) in 2013. We used baseline data from Engage, a cohort of GBM recruited by respondent-driven sampling, to examine patterns of combination HIV prevention use among Montreal GBM since PrEP became available. Latent class analysis, stratified by HIV status, was used to categorize GBM by self-reported use of biomedical and behavioural prevention strategies. Correlates of resulting classes were identified using multinomial logistic regression. Among HIV-negative/unknown GBM (n = 968), we identified four classes: low use of prevention (32%), condoms (40%), seroadaptive behaviour (21%), and biomedical (including PrEP; 7%). Those using prevention (condoms, seroadaptive behaviour, and biomedical) had a higher number of anal sex partners and were more likely to report a recent sexually transmitted infection diagnosis. GBM using biomedical prevention also had a higher level of formal education. Among GBM living with HIV (n = 200), we identified three classes: mainly antiretroviral treatment (ART) with viral suppression (53%), ART with viral suppression and condoms (19%), and ART with viral suppression and seroadaptive behaviour (18%). Again, the number of anal sex partners was higher among those using condoms and seroadaptive behaviours. Our findings show antiretroviral-based prevention, either alone or in combination with other strategies, is clearly a component of the HIV prevention landscape for GBM in Montreal. Nevertheless, PrEP uptake remains low, and there is a need to promote its availability more widely.

Using cross-sectional survey data (Engage, 2017–2018) from 1,137 men who have sex with men, ≥16 years old, in Montreal, we compared observed human immunodeficiency virus (HIV) seroconcordance in previous-6-months’ sexual partnerships with what would have been observed by chance if zero individuals serosorted. Of 5 recent partnerships where both individuals were HIV-negative, we compared observed concordance in preexposure prophylaxis (PrEP) use with the counterfactual if zero individuals selected partners based on PrEP use. We estimated the concordance by chance using a balancing-partnerships approach assuming proportionate mixing. HIV-positive respondents had a higher proportion of HIV-positive partners (66.4%, 95% confidence interval (CI): 64.0, 68.6) than by chance (23.9%, 95% CI: 23.1, 24.7). HIV-negative respondents (both on and not on PrEP) had higher proportions of HIV-negative partners (82.9% (95% CI: 81.1, 84.7) and 90.7% (95% CI: 89.6, 91.7), respectively) compared with by chance (76.1%, 95% CI: 75.3, 76.9); however, those on PrEP had a higher proportion of HIV-positive partners than those not on PrEP (17.1% (95% CI: 15.3, 18.9) vs. 9.3% (95% CI: 8.3, 10.4). Those on PrEP also had a higher proportion of partners on PrEP among their HIV-negative partners (50.6%, 95% CI: 42.5, 58.8) than by chance (28.5%, 95% CI: 27.5, 29.4). The relationship between PrEP and sexual-mixing patterns demonstrated by less population-level serosorting among those on PrEP and PrEP-matching warrants consideration during PrEP roll-out.

Objectives Respondent-Driven Sampling (RDS) is a variant of link-tracing, a sampling technique for surveying hard-to-reach communities that takes advantage of community members' social networks to reach potential participants. While the RDS sampling mechanism and associated methods of adjusting for the sampling at the analysis stage are well-documented in the statistical sciences literature, methodological focus has largely been restricted to estimation of population means and proportions, while giving little to no consideration to the estimation of population network parameters. As a network-based sampling method, RDS is faced with the fundamental problem of sampling from population networks where features such as homophily (the tendency for individuals with similar traits to share social ties) and differential activity (the ratio of the average number of connections by attribute) are sensitive to the choice of a sampling method. Methods Many simple approaches exist to generate simulated RDS data, with specific levels of network features (mainly homophily and differential activity), where the focus is on estimating means and proportions (Gile 2011; Gile et al. 2015; Spiller et al. 2018). However, recent findings on the inconsistency of estimators of network features such as homophily in partially observed networks (Crawford et al. 2017; Shalizi and Rinaldo 2013) raise the question of whether those target features can be recovered using the observed RDS data alone – as recovering information about these features is critical if we wish to condition upon them. In this paper, we conduct a simulation study to assess the accuracy of existing RDS simulation methods, in terms of their abilities to generate RDS samples with the desired levels of two network parameters: homophily and differential activity. Results The results show that (1) homophily cannot be consistently estimated from simulated RDS samples and (2) differential activity estimators are more precise when groups, defined by traits, are equally active and equally represented in the population. We use this approach to mimic features of the Engage Study, an RDS sample of gay, bisexual and other men who have sex with men in Montréal, Canada. Conclusions In this paper, we highlight that it is possible, in some cases, to simulate population networks by mimicking the characteristics of real-world RDS data while retaining accuracy and precision for target network features in the samples.

Background Awareness, availability, and public funding of pre-exposure prophylaxis (PrEP) has increased substantially since it was approved by Health Canada in 2016 but policies and guidelines vary by province. Given the dynamic nature of PrEP policy and promotion, we sought to determine awareness and use of PrEP among gay, bisexual, and other men who have sex with men (gbMSM) in Vancouver, Toronto, and Montreal. Methods Beginning in 02/2017, sexually-active gbMSM ≥16 years and living in Vancouver, Toronto, or Montreal were recruited into a cohort study using respondent-driven sampling (RDS). Data are included up to 08/2018. At study visits every 6 months (Vancouver) or 12 months (Toronto, Montreal), participants completed a computer-assisted self-interview which included questions on PrEP awareness and use in the past 6 months (P6M). We used RDS-adjusted, general estimating equations accounting for two levels of clustering (RDS recruitment chain; participant) to evaluate temporal trends (monthly prevalence) of awareness and P6M usage of PrEP among HIV-negative participants. Results 1619 HIV-negative gbMSM completed 2074 study visits (1205 Montreal, 285 Toronto, 584 Vancouver). Over the course of the study, PrEP awareness significantly increased among gbMSM in Montreal from 62.6% during the first 6-month period to 84.8% during the last 6-month period (OR:1.07, 95%CI:1.02–1.12, per month); awareness remained consistent in Toronto (89.8%–96.0%, ns) and Vancouver (84.5%–95.0%, ns). Use of PrEP increased significantly in all three sites: Montreal, 10.5% during the first 6-month period to 30.9% during the last 6-month period (OR:1.06, 95%CI:1.02–1.11); Toronto, 12.5% to 23.3% (OR:1.15, 95%CI:1.02–1.30); Vancouver, 11.4% to 35.2% (OR:1.16, 95%CI:1.06–1.27). Conclusion Awareness of PrEP appears to be ≥85% among HIV-negative gbMSM across all three cities. Even though provincial policy and programs differ greatly in availability and cost of PrEP, use of PrEP increased in all sites during the course of the study. Disclosure No significant relationships.

Background: Sexual mixing patterns influence HIV transmission dynamics. We quantified the population-level sexual mixing by two attributes (HIV status and pre-exposure prophylaxis (PrEP) use). Methods: We used data from Engage-Montreal (2017-2018), a cross-sectional survey of men who have sex with men (MSM) ≥16 year-old recruited using respondent-driven sampling. MSM with ≥1 anal/oral sex partners in the past 6 months (P6M) reported their own and partners' HIV status and PrEP use. Within P6M-partnerships across all MSM, we compared observed seroconcordance to what would have been expected by chance under proportionate mixing-if zero individual serosort. Within recent partnerships where both individuals were HIV-negative, we compared observed concordance in PrEP use at last sex to that expected by chance. We used chi-squared tests for comparisons, and calculated the excess fraction of concordance beyond chance. Findings: Of the 11,883 P6M-partnerships by 1137 respondents, 56.3% comprised partners' of known-status. Compared with by chance and among partners of known-status, HIV-positive respondents (n=207) had a higher proportion of HIV-positive partners (66.4% vs. 23.9%; p

This paper presents data from two studies that evaluated 5-y and 10-y persistence of antibodies against hepatitis B (HBV) surface antigen (anti-HBs) and immune response to an HBV vaccine challenge in children and adolescents who had received three doses of a HBV vaccine in infancy as part of routine clinical practice [NCT00519649/NCT00984139]. Anti-HBs antibody concentrations ≥ 10 mIU/ml persisted in 83.3% (95% confidence interval [CI]: 78.5–87.5) and 78.3% (95% CI: 73.1–83.0) of subjects aged 7–8 y and 12–13 y, respectively 5–10 y after infant vaccination. One month postchallenge dose, 98.2% (95% CI: 95.9–99.4) and 93.7% (95% CI: 90.2–96.2) of subjects in the two age groups, respectively had anti-HBs antibody concentrations ≥ 100 mIU/ml. Overall, 99.6% (95% CI: 98–100) and 97.2% (95% CI: 94.5–98.8) of subjects aged 7–8 y and 12–13 y mounted an anamnestic response to the HBV challenge dose, which was well-tolerated. Healthy children aged 7–8 y and adolescents aged 12–13 y received three doses of a monovalent pediatric HBV vaccine (10 μg of HBsAg) before 18 mo of age. Serum samples collected before and one month post-HBV vaccine challenge dose were tested for anti-HBs antibody concentrations. Safety assessments were made for the HBV vaccine challenge dose. A three-dose childhood HBV immunization regimen induced persistence of antibodies against HBV infection for 10 y, up to adolescence. This vaccination regimen also conferred long-term immune memory against HBV as evidenced by the strong anamnestic response to the HBV vaccine challenge, despite waning anti-HBs antibody levels.

Autonomic dysfunction tends to improve over time after acute myocardial infarction (MI), but the clinical significance of autonomic remodeling is not well known.The purpose of this study was to test the hypothesis that the amount of recovery of autonomic function early after MI is associated with a risk for serious arrhythmias.The prognostic significance of autonomic remodeling after MI was assessed in one post-MI cohort [Cardiac Arrhythmia and Risk Stratification after Myocardial Infarction (CARISMA)] and validated in a second cohort [Risk Estimation After Infarction, Noninvasive Evaluation (REFINE)]. Changes in heart rate variability (DeltaHRV) and heart rate turbulence (DeltaHRT) were measured from 24-hour ECG recordings performed early (5-21 days) and later (6 weeks) after MI in CARISMA (n = 312). DeltaHRV and DeltaHRT were similarly measured from early (2-4 weeks) and later (10-14 weeks) post-MI recordings in REFINE (n = 322).HRV and HRT increased over time in both cohorts. Attenuated recovery of autonomic function, defined as DeltaHRT slope2.0 ms/RR, was associated with a 9.4-fold (95% confidence interval 1.2-71.6; P = .03) higher risk of ECG-documented sustained ventricular tachycardia or ventricular fibrillation in CARISMA and a 7.0-fold (95% confidence interval 1.6-29.6; P = .009) higher risk of fatal or near-fatal events in REFINE. Changes in HRV and HRT were not predictive of nonarrhythmic death in either cohort.Attenuated recovery of autonomic function early after MI consistently predicts a higher risk of fatal or near-fatal arrhythmic events. A lack of improvement in HRT early after MI appears to be a specific marker for serious arrhythmic events.

Aims To evaluate clinical and arrhythmic outcomes in post-infarction cardiomyopathy patients implanted with a defibrillator (ICD) for primary prevention of sudden death. Methods and results The SEARCH-MI registry is a European multi-centre, prospective, observational study enrolling patients after myocardial infarction, chronic left ventricular dysfunction and an ICD implanted for primary prevention of sudden death. Data on 556 patients with at least one recorded follow-up are presented. Survey to Evaluate Arrhythmia Rate in High-risk MI (SEARCH-MI) patients were sicker than those enrolled in MADIT-II with higher New York Heart Association class and left bundle branch block. Total mortality was 10.4%. Close to one-third (30%) of patients experienced episodes of sustained ventricular arrhythmia. One-quarter (23%) received at least one appropriate therapy and 10% inappropriate therapy. Gender (25% males vs. 5% females, P = 0.0009) and history of non-sustained ventricular tachycardia (24% with vs. 18% without P = 0.037) were predictive of appropriate ventricular therapy. Conclusion SEARCH-MI represents the current clinical management of post-MI patients with left ventricular dysfunction indicated to defibrillator implant for primary prevention. European routine clinical practice was influenced by landmark trials and guidelines which impacted on the implantation of cardiac resynchronization therapy in over 25% of such patients. Non-sustained ventricular tachycardia identifies subjects with a higher incidence of appropriate ICD therapy.

Aims Radiofrequency ablation (RFA) of cavotricuspid isthmus (CTI)-dependent atrial flutter can be performed using various types of ablation catheters. Recent evaluations comparing externally cooledtip RFA (ecRFA) catheters and large-tip (8 mm) catheters found that ecRFA catheter may have a higher efficacy for CTI ablation. The aim of this prospective study was to compare both catheters by stratifying on CTI morphology in order to explain, in part, the discrepancies between previous randomized studies, and to validate predictive factors of difficult CTI ablation on clinical, echocardiographic, and angiographic data. Methods and results Over a period of 24 months, 281 patients were included and stratified on CTI morphology: ‘straight’, ‘concave’, and ‘pouch-like recess’. In straight CTI (n ¼ 150), the duration of application time with a median of 6 min [interquartile range (IQR) 4–9] vs. a median of 12 min (IQR 16–19; P , 0.0001) and the duration of X-ray exposure with a median of 6 min (IQR 4.4–9.7) vs. a median of 10.4 min (IQR 7–17; P , 0.0001) were significantly lower with an 8 mm-tip when compared with ecRFA catheter. In contrast, in concave CTI (n ¼ 95), a trend towards both shorter application time with a median of 12.5 min (IQR 6–23) vs. a median of 19 min (IQR 7–28; P ¼ 0.08) and X-ray duration exposure with a median of 10.4 min (IQR 6–20) vs. a median of 13 min (IQR 8–24; P ¼ 0.08) with an ecRFA catheter when compared with 8 mm-tip catheter were evidenced. No significant difference was shown between 8 mm-tip and ecRFA catheters in the pouch-like recess group (n ¼ 36). Predictive factors of difficult ablation include right CTI length and morphology. Conclusion This study demonstrates that the 8 mm-tip catheter is more effective for ablation in case of a straight angiographic isthmus morphology and that the ecRFA catheter tends to be more effective in case of concave angiographic isthmus morphology. Thus, angiographic isthmus evaluation may predict both the effectiveness of an RF catheter, and the risk of an expensive crossover. These data may explain, in part, the discrepancies of previous studies comparing both catheters.

Little data is available concerning the invasive treatment of atrial flutter (AFL) in elderly patients. The purpose of this prospective study was to evaluate the risks, safety, and follow-up of radiofrequency (RF) catheter ablation of common AFL in patients >75 years old (n = 61) (Group I) compared to patients younger than 75 years (n = 187) (Group II). The study population consisted of 248 patients (81% men/19% women), 21 to 96 years old (mean 66.3 +/- 12 years) with AFL, referred for RF from June 1999 to June 2001. RF endpoint was the assessment of the bidirectional block. The cumulative risk of atrial fibrillation (AF) was analyzed by the Kaplan-Meier method and log-rank test. The mean follow-up was 12.4 +/- 9 months. No complication occurred. Group I (80.1 +/- 4.5 years) did not differ significantly from Group II (61 +/- 11 years) regarding: AF history before ablation (34.4% vs 39.8%), structural heart disease (54% vs 42%), LVEF (57%+/- 12% vs 58%+/- 12%), left atrial size (43.8 +/- 7 vs 42.5 +/- 7), cava-tricuspid isthmus dimension (40 +/- 10 vs 39 +/- 4 mm), bidirectional block (100% vs 96.2%), RF application (12.5 +/- 10 vs 13.5 +/- 12 minutes), AFL recurrence (3.3% vs 5.3%), antiarrhythmic agents at hospital discharge (34.4% vs 38.9%), mean follow-up (12 +/- 9 vs 13 +/- 9 months) and AF occurrence (29.5% vs 20.3%; P = 0.2). Of these, the incidence of AF in patients without prior history (n = 150) was 7 (18%) of 39 for Group I and 11 (10%) of 111 for Group II (P = 0.1) after follow-up. Catheter ablation of AFL in very elderly patients appears to be a reasonable approach regarding feasibility, effectiveness, and low procedural risk.

Background — The reentrant mechanism of postinfarct ventricular tachycardia (VT) has been documented by surgical mapping analysis, but little is known about postinfarct VT circuits and the characteristics of their related protected isthmus with the use of 3D catheter mapping systems. Methods and Results — A 3D electroanatomic mapping was performed in 21 patients with well-tolerated, postinfarct, sustained VT. In total, 33 episodes of tachycardia (mean cycle length 432±74 ms) were induced and mapped. Complete maps demonstrated macroreentrant circuits with 1 loop (n=8) or 2 loops (n=25) rotating around a protected isthmus bounded by 2 approximately parallel conduction barriers that consisted of a line of double potentials, a scar area, or the mitral annulus. A total of 26 critical isthmi were identified for the 33 VTs mapped, with the same isthmus being shared by 2 to 4 different tachycardic morphologies in 5 patients. On average, isthmi were 31±7 mm long (ranging from 18 to 41 mm) and 16±8 mm wide (ranging from 6 to 36 mm) and harbored diastolic electrograms. The isthmus axis was oriented parallel to the mitral annulus plane in perimitral circuits and perpendicular to the mitral annulus plane in all other circuits. Linear radiofrequency ablation performed across the most accessible part of the isthmus prevented the recurrence of tachycardia in 19 patients (90%) with a follow-up at 16±8 months. Conclusions — Detailed 3D electroanatomic mapping is helpful in reconstructing postinfarct VT circuits and in defining the characteristics of their related protected isthmi. The wide range of isthmus width values supports the need of linear radiofrequency lesions to eliminate the reentrant substrate of postinfarct VTs.

Accessory Pathway Localization. Introduction: The purpose of this study was to evaluate the accuracy and limitations of published algorithms using the 12-lead ECG to localize AV accessary pathways (APs). Methods and Results: The 11 relevant algorithms found in the literature (MEDLINE database and major scientific sessions) were tested on a series of 266 consecutive patients who successfully underwent radiofrequency catheter ablation of a single overt AV AP. The positive predictive values (PPV) of the algorithms in applicable patients were significantly lower for algorithms with > 6 accessory location sites (40.6%± 10.9% vs 61.2%± 8.0%; P < 0.03) and show a tendency for algorithms not relying on delta wave polarity but on QRS polarity only (36.6%± 11.2% vs 52.3%± 13.1%; P = 0.09). The PPV in applicable patients is related to the AP location (P < 0.001) and ranked from the highest to the lowest as follows: left lateral (mean PPV = 86.3%), posteroseptal (mean PPV = 65.2%), right anteroseptal (mean PPV = 45.2%), and right posterolateral (mean PPV = 23.4%). Conclusion: Our study suggests that the accuracy of algorithms relying on the 12-lead ECG depends on AP locations as defined in the algorithms and on the number of AP sites. The accuracy tends to be lower when delta wave polarity is not included in the algorithm's architecture. This should be considered when using these algorithms or when building new ones.

UNLABELLED This study evaluated the impact of the atrioventricular delay (AVD) on the pulmonary venous flow pattern (PVFP). METHODS Transthoracic Doppler PVFP were obtained during atrial and ventricular pacing at a fixed rate of 70 beats/min in 20 patients equipped with a DDD pacemaker, diastolic dysfunction linked to an impaired relaxation, a mean ejection fraction of 49%, and AV block. Two subgroups were analyzed equally: group I: seven patients with a normal ejection fraction and group II: 13 patients with decreased ejection fraction. Three different AVDs were studied: short (50 ms), intermediate (150 ms), and long (250 ms). RESULTS As the AVD increased, the diastolic filling time and the peak atrial reverse flow wave decreased (P < 0.001). There was a decreasing D wave and no significant change in the peak velocity of the S wave. The S wave became biphasic in all patients at the longest AVD of 250 ms. The systolic (S) velocity time integral (VTI) of the pulmonary wave and the systolic/total PVF-VTI ratio increased significantly (P < 0.001). A similar response was seen in both group of patients. CONCLUSIONS These data correlated the AVD with PVFP, supplying critical systolic information completing the diastolic data obtained from mitral Doppler patterns. These systolic measurements were especially useful for patients with heart failure and a DDD pacemaker, in order to obtain the longest diastolic filling time at the lowest atrial pressure.

The objective of this study was to assess the effects ofradiofrequency energy application on implanted pacemaker functions.Radiofrequency (RF) catheter ablation may cause pacemaker dysfunction dueto electromagnetic interferences. The effects of RF on pacemaker behaviorwere studied in a series of 38 pacemakers, implanted 18 ± 26 monthsprior to a RF procedure using either a right ventricular approach (AV nodeablation, n = 35) or a left ventricular approach (left concealedaccessory pathway ablation, n = 1; VT ablation, n = 2). The38 patients (mean age 65 ± 9 years) included 20 men and 18 women.Before energy applications, the 23 different pacemaker models wereprogrammed to the VVI mode at the lowest available rate. The continuoussurface ECG was recorded throughout the procedure. Thorough testing of thedevices was performed before and after each RF delivery. Unusual pacemakerresponses occurred in 20 of the 38 cases studied (53%). The impactof RF delivery was unpredictable, and variable dysfunctions were observedat different times for a given patient or could vary for a given model.Unusual pacemaker responses included pacemaker inhibition (n = 8), untoggled backup mode (n = 3), electromagnetic interference noisemode (n = 3), temporary RF-induced pacemaker tachycardia (n =2), erratic behavior (n = 1), oversensing of RF onset and offset (n= 8), and transient loss of ventricular capture, (n = 1).Postablation, most devices automatically toggled back to fullfunctionality. The three devices in the untoggled backup mode had to bereprogrammed to obtain normal operations. At the end of the procedure,pacing thresholds remained unchanged in all but one patient, in whom theincrease in ventricular threshold was due to a nicked lead. In conclusion,implanted pacemakers frequently exhibit transient, unpredictable responsesto RF energy application. Although all pacemaker functions were restored postablation, some devices had to be reset manually. The anomalies observedduring the RF application argue for the simultaneous use of an externalpacemaker in pacing-dependent patients.

Hepatitis B vaccine has been available worldwide since the mid-1980s. This vaccine was evaluated in a clinical trial in Thailand, conducted on subjects born to hepatitis B surface antigen positive and hepatitis B e-antigen positive mothers and vaccinated according to a 4-dose schedule at 0, 1, 2 and 12 mo of age and a single dose of hepatitis B immunoglobulin concomitantly at birth. All enrolled subjects seroconverted and were followed for 20 y to assess the persistence of antibody to the hepatitis B surface antigen (anti-HBs) (NCT00240539). At year 20, 64% of subjects had anti-HBs antibody concentrations ≥ 10 milli-international units per milli liter (mIU/ml) and 92% of subjects had detectable levels (≥ 3.3 mIU/ml) of anti-HBs antibodies. At year 20, subjects with anti-HBs antibody titer < 100 mIU/ml were offered an additional dose of hepatitis B virus (HBV) vaccine to assess immune memory (NCT00657657). Anamnestic response to the challenge dose was observed in 96.6% of subjects with an 82-fold (13.2 to 1082.4 mIU/ml) increase in anti-HBs antibody geometric mean concentrations. This study confirms the long-term immunogenicity of the 4-dose regimen of the HBV vaccine eliciting long-term persistence of antibodies and immune memory against hepatitis B for up to at least 20 y after vaccination.

This paper presents data from two studies that evaluated 5-y and 10-y persistence of antibodies against hepatitis B (HBV) surface antigen (anti-HBs) and immune response to an HBV vaccine challenge in children and adolescents who had received three doses of a HBV vaccine in infancy as part of routine clinical practice [NCT00519649/NCT00984139]. Anti-HBs antibody concentrations ≥ 10 mIU/ml persisted in 83.3% (95% confidence interval [CI]: 78.5–87.5) and 78.3% (95% CI: 73.1–83.0) of subjects aged 7–8 y and 12–13 y, respectively 5–10 y after infant vaccination. One month postchallenge dose, 98.2% (95% CI: 95.9–99.4) and 93.7% (95% CI: 90.2–96.2) of subjects in the two age groups, respectively had anti-HBs antibody concentrations ≥ 100 mIU/ml. Overall, 99.6% (95% CI: 98–100) and 97.2% (95% CI: 94.5–98.8) of subjects aged 7–8 y and 12–13 y mounted an anamnestic response to the HBV challenge dose, which was well-tolerated. Healthy children aged 7–8 y and adolescents aged 12–13 y received three doses of a monovalent pediatric HBV vaccine (10 μg of HBsAg) before 18 mo of age. Serum samples collected before and one month post-HBV vaccine challenge dose were tested for anti-HBs antibody concentrations. Safety assessments were made for the HBV vaccine challenge dose. A three-dose childhood HBV immunization regimen induced persistence of antibodies against HBV infection for 10 y, up to adolescence. This vaccination regimen also conferred long-term immune memory against HBV as evidenced by the strong anamnestic response to the HBV vaccine challenge, despite waning anti-HBs antibody levels.

Background and objectives Antibody persistence and immune memory against hepatitis A (HAV) in adults in a low endemicity country, 15 y after immunisation with two doses of HAV vaccine has been demonstrated. This communication provides additional information on antibody persistence up to Year 17 from two of the longest follow-up studies [NCT00289757/NCT00291876]. Methods In two double-blind primary studies, healthy adults aged 17−40 y and 21−40 y, respectively received two doses of the HAV vaccine following a 0,6 mo or 0,12 mo schedule. Anti-HAV antibody concentrations were measured using an enzyme-linked immunoassay (cut-off: 15mIU/ml) at Year 16 and Year 17. Subjects who became seronegative (anti-HAV < 15mIU/ml) since previous reporting were offered a challenge dose, with anti-HAV antibody concentration measurements at Day 14 and Day 30 thereafter. Results At Year 17, 100% and 96.7% of subjects remained seropositive for anti-HAV antibodies following the 0, 6 mo and 0, 12 mo regimens, respectively (GMCs: 278mIU/ml and 369mIU/ml). One subject who became seronegative at Year 16 received a HAV challenge dose within the next 12 mo and mounted an anamnestic response. The challenge dose was well-tolerated. Conclusions Both HAV immunisation regimens (0,6 mo and 0,12 mo) induced persistence of vaccine-induced antibodies against HAV for at least 17 y after primary vaccination.

We appreciate the very relevant comments by Ravensbergen and colleagues, and agree that the Cardiac Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA) Study1 had several limitations. As we also pointed out, the main limitation, regarding the definition and diagnosis of tachyarrhythmias, was that the rate had to be ≥125 beats per minute for every beat of at least 16 consecutive beats. Thus, tachyarrhythmias of 16 consecutive beats, and with varying R-R intervals longer than 480 ms, could not be recorded by the implantable …

Three doses of the investigational AS02(v)-adjuvanted hepatitis B virus (HBV) vaccine HB-AS02 have been shown to induce more rapid seroprotection and higher anti-HBs antibody concentrations in patients with renal insufficiency than four doses of FENDrix™ (HB-AS04), an adjuvanted HBV vaccine licensed in Europe for use in this population. This study evaluated persistence of immune response up to 36 months after primary vaccination.In this open, international, Phase III follow-up study, 151 pre-dialysis, peritoneal dialysis and hemodialysis patients ≥15 years of age received HB-AS02 at 0, 1, 6 months and 149 received HB-AS04 at 0, 1, 2, 6 months. Of these, 99 and 80 returned at Month 36, 76 and 62 of whom were eligible for inclusion in the Long-Term According-To-Protocol (LT-ATP) cohort for descriptive analysis of antibody persistence (mean age: 65.6 years).At Month 36, 89.5% of subjects in the HB-AS02 group and 72.6% of those in the HB-AS04 group had anti-HBs antibody concentrations ≥10 mIU/ml. Anti-HBs antibody concentrations were ≥100 mIU/ml in 82.9% and 35.5% of subjects, respectively. Anti-HBs geometric mean antibody concentrations were higher in the HB-AS02 group over the 36 months of follow-up. An exploratory "time to boost" analysis confirmed that subjects who received HB-AS02 were 2.54 times more likely than those who received HB-AS04 to have anti-HBs antibody concentrations ≥10 mIU/ml at Month 36 (p=0.013 [95% CI: 1.22, 5.31]).HB-AS02 candidate vaccine induces high and persistent anti-HBs antibody levels in pre-dialysis, peritoneal dialysis and hemodialysis patients, potentially reducing the need for booster doses in this population.

Aims The present study aimed to assess whether there are differences in risk indicators for perpetuating ventricular tachyarrhythmias (pVT) and self-terminating ventricular tachyarrhythmias (stVT). Methods and results Patients with acute myocardial infarction (AMI) and baseline left ventricular ejection fraction ≤40% ( n = 292) received an implantable electrocardiogram loop recorder from 5 to 21 days after AMI and were followed up for 24 months to document arrhythmic events in the Cardiac Arrhythmias and Risk Stratification after Acute Myocardial Infarction (CARISMA) study. Several risk markers, such as the inducibility to sustained ventricular tachycardia during programmed electrical stimulation (PES), the signal-averaged ECG QRS duration (SAECG-QRS), heart rate variability (HRV) and turbulence (HRT), T-wave alternans, and non-sustained ventricular tachycardia on Holter were analysed at 6 weeks after the AMI. During the follow-up, 26 patients (9%) experienced an stVT (≥16 beats and

The duration of protection after vaccination with reduced antigen content diphtheria, tetanus and acellular pertussis vaccines (Tdap) is not known. Long-term post-vaccination serological data will help to improve understanding of the duration of humoral immunity and guide vaccination policy for the timing of repeat dose administration. The persistence of antibodies to Tdap antigens was measured 3 years after vaccination of adults 19-64 years of age with one of 2 Tdap vaccines (Boostrix(®), GlaxoSmithKline Biologicals; Tdap-B: or Adacel(®), Sanofi Pasteur; Tdap-A). In both groups, geometric mean concentrations for antibodies to diphtheria, tetanus, and pertussis vaccine antigens were decreased at year 3 relative to levels observed 1 month and 1 year following vaccination, but remained higher than pre-vaccination levels. Seroprotection rates for diphtheria and tetanus remained high for both Tdap vaccines (for diphtheria, 96.9% and 97.8% for the Tdap-B and Tdap-A groups, respectively; for tetanus, 98.1% and 99.6%, respectively).

Background Older adults, especially those over 65 years, are at risk of more severe morbidity from diphtheria, tetanus and pertussis and may transmit pertussis to unvaccinated or not yet fully vaccinated infants, but data on their response to reduced-antigen-content tetanus, diphtheria and acellular pertussis (dTpa) vaccines are lacking. Methods A sub-analysis pooled immunogenicity results in 293 adults aged 55+ years (mean age 64.4 years) from four randomised, controlled clinical trials of dTpa vaccine (Boostrix®, GlaxoSmithKline Biologicals) with or without IPV co-administration, or dTpa-IPV (Boostrix® IPV). Results Seroprotective antibody levels were achieved by 82.8% for diphtheria and 94.5% for tetanus. For pertussis antigens, the booster response rate, defined as initially seronegative subjects [

Background High-degree atrioventricular block (HAVB) is a frequent complication in the acute stages of a myocardial infarction associated with an increased rate of mortality. However, the incidence and clinical significance of HAVB in late convalescent phases of an AMI is largely unknown. The aim of this study was to assess the incidence and prognostic value of late HAVB documented by continuous electrocardiogram (ECG) monitoring in post-AMI patients with reduced left ventricular function. Methods The study included 286 patients from the CARISMA study with AMI and left ventricular ejection fraction of 40% or less. An insertable loop recorder was implanted 5 to 21 days after AMI for incessant arrhythmia surveillance. Furthermore, ECG documentation was supplemented by a 24-hour Holter monitoring conducted at week 6 post-AMI. The clinical significance of HAVB occurring more than 21 days after AMI was examined with respect to development of major heart failure events and major ventricular tachyarrhythmic events. Results During a median follow-up of 1.9 years (interquartile range 0.9-2.0), late HAVB was documented in 30 patients. The risk of major heart failure events (hazard ratio [HR] 4.08 [1.38-12.09], P = .01) and major ventricular tachyarrhythmic events (HR = 5.41 [1.88-15.58], P = .002) were significantly increased in patients who developed late HAVB. Conclusion High-degree atrioventricular block documented by continuous ECG monitoring occurring more than 3 weeks after AMI is a frequent complication in post-AMI patients with left ventricular dysfunction. Furthermore, HAVB is associated with ominous prognostic implications of both potentially lethal arrhythmias and heart failure.

Background— Knowledge about the incidence of cardiac arrhythmias after acute myocardial infarction has been limited by the lack of traditional ECG recording systems to document and confirm asymptomatic and symptomatic arrhythmias. The Cardiac Arrhythmias and Risk Stratification After Myocardial Infarction (CARISMA) trial was designed to study the incidence and prognostic significance of arrhythmias documented by an implantable cardiac monitor among patients with acute myocardial infarction and reduced left ventricular ejection fraction. Methods and Results— A total of 1393 of 5869 patients (24%) screened in the acute phase (3 to 21 days) of an acute myocardial infarction had left ventricular ejection fraction ≤40%. After exclusions, 297 patients (21%) (mean±SD age, 64.0±11.0 years; left ventricular ejection fraction, 31±7%) received an implantable cardiac monitor within 11±5 days of the acute myocardial infarction and were followed up every 3 months for an average of 1.9±0.5 years. Predefined bradyarrhythmias and tachyarrhythmias were recorded in 137 patients (46%); 86% of these were asymptomatic. The implantable cardiac monitor documented a 28% incidence of new-onset atrial fibrillation with fast ventricular response (≥125 bpm), a 13% incidence of nonsustained ventricular tachycardia (≥16 beats), a 10% incidence of high-degree atrioventricular block (≤30 bpm lasting ≥8 seconds), a 7% incidence of sinus bradycardia (≤30 bpm lasting ≥8 seconds), a 5% incidence of sinus arrest (≥5 seconds), a 3% incidence of sustained ventricular tachycardia, and a 3% incidence of ventricular fibrillation. Cox regression analysis with time-dependent covariates revealed that high-degree atrioventricular block was the most powerful predictor of cardiac death (hazard ratio, 6.75; 95% confidence interval, 2.55 to 17.84; P Conclusions— This is the first study to report on long-term cardiac arrhythmias recorded by an implantable loop recorder in patients with left ventricular ejection fraction ≤40% after myocardial infarction. Clinically significant bradyarrhythmias and tachyarrhythmias were documented in a substantial proportion of patients with depressed left ventricular ejection fraction after acute myocardial infarction. Intermittent high-degree atrioventricular block was associated with a very high risk of cardiac death. Clinical Trial Registration— URL: http://www.ClinicalTrials.gov , Unique identifier: NCT00145119.

The incidence and risk associated with new-onset atrial fibrillation (AF) occurring after discharge in patients with acute myocardial infarction (MI) remains unknown.This study sought to describe the incidence and clinical risk associated with postdischarge new-onset AF in post-MI patients with left ventricular systolic dysfunction.The population included 271 post-MI patients with left ventricular ejection fraction ≤ 40% and no history of previous AF from the Cardiac Arrhythmias and Risk Stratification after Acute Myocardial Infarction (CARISMA) study. All patients were implanted with an implantable cardiac monitor and followed up every 3 months for 2 years. Major cardiovascular events were defined as reinfarction, stroke, hospitalization for heart failure, or death.The risk of new-onset AF is highest during the first 2 months after the acute MI (16% event rate) and decreases until month 12 post-MI, after which the risk for new-onset AF is stable. The risk of major cardiovascular events was increased in patients with AF events ≥ 30 seconds (hazard ratio [95% CI] = 2.73 [1.35 to 5.50], P = .005), but not in patients with AF events lasting30 seconds (hazard ratio [95% CI] = 1.17 [0.35 to 3.92], P = .80). More than 90% of all recorded AF events were asymptomatic.Using an implantable cardiac monitor, the incidence of new-onset AF was found to be 4-fold higher than earlier reported. In the study population, in which treatment with beta-blockers was optimized, the vast majority of AF events were asymptomatic, emphasizing the importance of using continuous monitoring for studies concerning AF in heart failure patients. A duration of 30 seconds or more identified clinically important AF episodes documented by an implantable cardiac monitor.

Predicting New-Onset AF. Background: Atrial fibrillation (AF) increases morbidity and mortality in patients with previous myocardial infarction and left ventricular systolic dysfunction. The purpose of this study was to identify patients with a high risk for new-onset AF in this population using invasive and noninvasive electrophysiological tests. Methods: The study included 271 patients from the Cardiac Arrhythmias and RIsk Stratification after Myocardial InfArction (CARISMA) study with an acute myocardial infarction (AMI) and left ventricular ejection fraction ≤40% without previous AF at enrollment. Within 21 days after the AMI, an implantable loop recorder was inserted and used to diagnose AF over the 2-year study duration. The following tests were performed: heart rate variability (HRV) and turbulence (HRT) analyses from repeated 24-hour Holter recordings, 2-dimensional (2D)-echocardiograms, exercise test, and programmed electrophysiologic stimulation. Results: A total of 101 patients (37%) developed AF during the study. Predictive measures included several indexes of HRV including reduced low-frequency (LF) power from spectral HRV analysis (adjusted HR = 1.6, P = 0.034), HRT slope ≤2.5 (HR = 1.6, P = 0.032) and Detrended Fluctuation Analysis (DFA1) from HRV analysis (HR = 1.8, P = 0.011); all are measures of cardiac autonomic nervous system dysfunction. Combined with age >60 years, low values for LF, HRT slope, and DFA1 provided a powerful risk score for prediction of new-onset AF (1–2 points: HR = 4.3, P = 0.001, 3–4 points: HR = 7.0, P < 0.001). Conclusion: Abnormal HRV and HRT parameters, which are associated with disturbances in the cardiac autonomic regulation, are associated with increased risk of new-onset AF independently of conventional clinical risk variables. (J Cardiovasc Electrophysiol, Vol. 21, pp. 983-990, September 2010)

Aims The aim of this study was to investigate the association between diastolic dysfunction and long-term occurrence of new-onset atrial fibrillation (AF) and cardiac events in patients with acute myocardial infarction (AMI) and left ventricular (LV) systolic dysfunction. Methods and results The study was performed as a substudy on the CARISMA study population. The CARISMA study enrolled 312 patients with an AMI and LV ejection fraction ≤40%. Patients were implanted with an implantable loop recorder and followed for 2 years. Sixty-two patients had a full echocardiographic assessment of the diastolic function using tissue Doppler analysis performed 6 weeks after the AMI. The endpoints were: (i) new-onset AF and (ii) major cardiovascular events (MACE) defined as re-infarction, stroke, or cardiovascular death. Twenty-four patients had diastolic dysfunction, whereas 38 patients had normal diastolic function. Diastolic dysfunction was associated with an increased risk of new-onset AF [HR = 5.30 (1.68–16.75), P = 0.005] and MACE [HR = 4.70 (1.25–17.75), P = 0.022] after adjustment for age, sex, NYHA class, and hypertension. Conclusion Diastolic dysfunction in post-MI patients with LV systolic dysfunction predisposes to new-onset AF and MACE.

Aims Device-related infections (DRI) are not well understood in patients implanted with a cardiac resynchronization therapy (CRT) device. The aims of this study were: (i) to evaluate the prevalence of CRT DRI; (ii) to establish the factors predictive of CRT DRI. Methods and results Between January 2001 and May 2007, CRT implantation was performed in 303 patients (247 men, 82%). The mean follow-up was 31 ± 19 months. Population characteristics were a mean age of 70 ± 10 years old; 56 female; aetiology includes (202 dilated and 101 ischaemic cardiomyopathy); NYHA class 3.2 ± 0.3; LVEF (26 ± 6%), and a QRS width of 171 ± 31 ms. Thirteen patients developed a DRI: endocarditis in four, pocket erosion in three, pocket abscess in five, and septicaemia in one. The prevalence of DRI was 4.3%. By univariate analysis, predictive factors of DRI were: procedure time (skin to skin: median of 85 vs. 57.5 min; P = 0.03), re-intervention (54 vs. 6.5%; P < 0.0001), haematoma (31 vs. 8.6% P = 0.01), lead dislodgement (23 vs. 6.2%; P = 0.03), dialysis (23.1 vs. 1.72%; P = 0.003), and procedure type [CRT-ICD (8.6%) vs. CRT PM (1.6%) or system up-grade (1.5%); P = 0.03]. Significant correlations were found between re-intervention and lead dislodgement ( r = 0.8; P < 0.001), haematoma ( r = 0.2; P < 0.001). Four independent predictive factors of DRI were identified as procedure time ( P = 0.002); dialysis ( P = 0.0001); re-intervention ( P = 0.006), and procedure type (CRT-ICD vs. other procedures; P = 0.01). Conclusion This study found that the prevalence of CRT DRI is close to 4.3% at 2.6 years (1.7% per year incidence). Four independent predictive factors of infections were identified including re-intervention, procedure time, dialysis, and primo CRT-ICD implantation. These parameters should be part of the risk–benefit evaluation in patients selected for CRT implantation.

Aims To determine whether risk stratification tests can predict serious arrhythmic events after acute myocardial infarction (AMI) in patients with reduced left ventricular ejection fraction (LVEF ≤ 0.40). Methods and results A total of 5869 consecutive patients were screened in 10 European centres, and 312 patients (age 65 ± 11 years) with a mean LVEF of 31 ± 6% were included in the study. Heart rate variability/turbulence, ambient arrhythmias, signal-averaged electrocardiogram (SAECG), T-wave alternans, and programmed electrical stimulation (PES) were performed 6 weeks after AMI. The primary endpoint was ECG-documented ventricular fibrillation or symptomatic sustained ventricular tachycardia (VT). To document these arrhythmic events, the patients received an implantable ECG loop-recorder. There were 25 primary endpoints (8.0%) during the follow-up of 2 years. The strongest predictors of primary endpoint were measures of heart rate variability, e.g. hazard ratio (HR) for reduced very-low frequency component (

Background. Changes in cardiac autonomic function have been documented after myocardial infraction (MI), but their significance is unknown. We assessed the amount of recovery of autonomic dysfunction after MI and its significance among the patients with depressed left ventricular ejection fraction (LVEF ≤ 0.40 - CARISMA and ≤ 0.50 - REFINE). Methods and Results. Changes in heart rate variability (dHRV) and turbulence (dHRT) were measured from 24-hour ECG recordings performed 5–21 days and again at six weeks post-MI in 312 patients included in the Cardiac Arrhythmias and Risk Stratification after Myocardial Infarction (CARISMA) study. The primary endpoint was sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) recorded by an implantable device. Non-arrhythmic death was a secondary endpoint. HRV and HRT measures increased significantly from baseline to six weeks post-AMI (p Conclusions. Autonomic function undergoes a substantial improvement early after MI, which is associated with vulnerability to VT or VF. A marked recovery of autonomic dysfunction protects from the occurrence of fatal or near-fatal arrhythmic events after MI despite depressed LVEF

Introduction: Implantable loop recorders (ILR) have an automatic arrhythmia detection feature that can be compromised by inappropriately detected episodes. This study evaluated a new ILR sensing and detection scheme for automatically detecting asystole, bradyarrhythmia, and tachyarrhythmia events, which is implemented in the next generation device (Reveal DX/XT). Methods and Results: The new scheme employs an automatically adjusting R-wave sensing threshold, enhanced noise rejection, and algorithms to detect asystole, bradyarrhythmia, and tachyarrhythmia. Performance of the new algorithms was evaluated using 2,613 previously recorded, automatically detected Reveal Plus episodes from 533 patients. A total of 71.9% of episodes were inappropriately detected by the original ILR, and at least 88.6% of patients had one or more inappropriate episodes, with most inappropriate detections due to R-wave amplitude reductions, amplifier saturation, and T-wave oversensing. With the new scheme, inappropriate detections were reduced by 85.2% (P < 0.001), with a small reduction in the detection of appropriate episodes (1.7%, P < 0.001). The new scheme avoided inappropriate detections in 67.4% of patients that had them with the original scheme. Conclusions: The new sensing and detection scheme is expected to substantially reduce the occurrence of inappropriately detected episodes, relative to that of the original ILR.

Background— There is no published randomized study comparing amiodarone therapy and radiofrequency catheter ablation (RFA) after only 1 episode of symptomatic atrial flutter (AFL). The aim of the Loire-Ardèche-Drôme-Isère-Puy-de-Dôme (LADIP) Trial of Atrial Flutter was 2-fold: (1) to prospectively compare first-line RFA (group I) versus cardioversion and amiodarone therapy (group II) after only 1 AFL episode; and (2) to determine the impact of both treatments on the long-term risk of subsequent atrial fibrillation (AF). Methods and Results— From October 2002 to February 2006, 104 patients (aged 78±5 years; 20 women) with AFL were included, with 52 patients in group I and 52 patients in group II. The cumulative risk of AFL or AF was interpreted with the use of Kaplan-Meier curves and compared by the log-rank test. Clinical presentation, echocardiographic data, and follow-up were as follows: age (78.5±5 versus 78±5 years), history of AF (27% versus 21.6%); structural heart disease (58% versus 65%), left ventricular ejection fraction (56±14% versus 54.5±14%), left atrial size (43±7 versus 43±6 mm), mean follow-up (13±6 versus 13±6 months; P =NS), recurrence of AFL (3.8% versus 29.5%; P P =0.3). Five complications (10%) were noted in group II (sick sinus syndrome in 2, hyperthyroidism in 1, and hypothyroidism in 2) and none in group I (0%) ( P =0.03). Conclusions— RFA should be considered a first-line therapy even after the first episode of symptomatic AFL. There is a better long-term success rate, the same risk of subsequent AF, and fewer secondary effects.

Radiofrequency catheter ablation (RFA) represents the first line therapy of the cavotricuspid isthmus-dependent atrial flutter (CTI-AFL) with a high efficacy and low secondary effects. RFA of CTI-dependent AFL can be performed by using various types of ablation catheters. Recent evaluations comparing externally cooled tip RFA (ecRFA) catheters and large-tip (8 mm) catheters have revealed that these catheters have a higher efficacy for CTI-AFL ablation compared to 4-mm catheters. The reliability of RFA catheters for AFL is variable and an optimal catheter selection may enhance the RFA effectiveness. The main goal of this article is to review the elements that improve the management of CTI RFA. Preliminary examinations of histopathologic and anatomical elements that may interfere with conventional CTI RFA are presented. Experimental studies concerning the electrobiology of large-tip and cooled-tip catheters are compared. The different catheter designs between cooled-tip and 8-mm-tip catheters are examined (size of the deflectable curve, rotation stability, and size of the distal nonsteerable catheter part) because of their critical role in CTI RFA results. A thorough review of clinical trials of each catheter is presented, and comparison of both catheters in this clinical setting is analyzed. In addition, the role of CTI morphology on AFL RF duration is underlined such as the value of right atrial angiography as an adjunct tool for CTI RFA catheter selection. Based on randomized studies, 8-mm-tip catheters seem to be more effective for ablation in case of straight angiographic isthmus morphology. On the other hand, ecRFA catheters appear to be more effective in cases of complex CTI anatomy or difficult CTI RFA. To reduce X-ray exposition and RFA application time, few studies report that CTI angiographic evaluation before RFA allows a catheter selection based on both CTI morphology and length. Moreover, preliminary data of randomized studies showed that an angiographic isthmus evaluation may predict both the effectiveness of a RFA catheter and the risk of an expensive catheter crossover.

International audience; BACKGROUND: Cooled-tip RFA (cRFA) and conventional 8-mm-tip catheters were found to be more effective and as safe as conventional 4-mm-tip catheters for atrial flutter (AFL) radiofrequency ablation (RFA), facilitating the rapid achievement of bi-directional isthmus block (BIB), but studies comparing cRFA and 8-mm-tip catheters are not randomized or results are discussed. Thus, we performed a meta-analysis of available randomized trials to evaluate the effectiveness in terms of primary success and procedure parameters. METHODS: Reports of trials were identified through a Medline, Embase, Current Contents, Cardline, and an extensive bibliography search. Trials that met the following criteria were included: (1) prospective, randomized, controlled, and open trials; (2) patients assigned to an 8-mm-tip or a cRFA catheter for AFL RFA; (3) endpoints events related to primary success rate (BIB achievement), and procedure parameters (number of RF applications, x-ray exposure and ablation duration). RESULTS: Seven trials met the inclusion criteria. They included 603 patients with established AFL randomized to an 8-mm-tip or cRFA catheter group. Comparing 8-mm groups with cRFA groups, the meta-analysis showed similar BIB achievement relative risk (RR) 0.96, 95% confidence interval (CI): 0.92 to 1.01, (P = 0.13); total RF application time weighted mean difference (WMD) 0.88, 95% CI: -0.36 to 2.12, (P = 0.16); duration of x-ray exposure (min) (WMD = 1.07, 95% CI: -0.81 to 0.295, (P = 0.26); ablation procedure duration (min) (WMD = 0.68, 95% CI: -3.37 to 4.73; P = 0.74). CONCLUSION: The present meta-analysis confirms that cooled-tip and large-tip catheters are equally efficient for cavotricuspid isthmus ablation with both similar primary success rates and procedure parameters.

Background Patients with syncope or near syncope of unknown etiology represent a great challenge to cardiologists. An initial symptomatic episode triggers a series of diagnostic analysis which remain unsatisfactory when negative. More invasive tools such as electrophysiologic testing yield only partial answers to risk stratification while the complementary implantable holter diagnostics are not usually considered until a recurrent episode is documented. Objective This study targets predictors of significant cardiac rhythmic events in patients with a reported episode of syncope or near syncope presenting with negative diagnostics and electrophysiologic study results (EPS). A significant cardiac rhythmic event was defined as a combined end-point of (1) symptomatic AV block; (2) symptomatic conduction abnormalities requiring pacemaker therapy; (3) symptomatic sustained ventricular arrhythmia; and (4) sudden death. Methods All patients undergoing EPS after a first episode of syncope or presyncope between January 1997 and December 2001 were included for analysis. The study population consisted of 329 pts (42.6% women), 21 to 96 years old (mean 70±15 years) referred for an EP study for syncope or near syncope. Results Of the 329 patients who underwent EPS, 305 (92.7%) had follow-up data. The population, mean age 70 (± 15 years) and composed of 42% women, presented with hypertension (51.5%), diabetes mellitus (14.4%), hypercholesterolemia (30%), tobacco use (35%), a familial history of coronary heart disease (22%), history of stroke (4%), history of MI (12%), history of atrial fibrillation (10%), structural heart disease (17.4%), left ventricular ejection fraction 61 (± 11%) and ECG abnormalities (37%). These anomalies included right (RBBB) or left (LBBB) bundle branch blocks, left anterior fascicular block (LAFB), left posterior fascicular block (LPFB), bifascicular block (RBBB+LAFB) and traces of myocardial infarction. The mean follow-up was 31±20 months with 5% of patients recording significant cardiac rhythmic events (15/305): AV block requiring pacemaker therapy in 7 patients, sinus dysfunction in 4, sudden death in 3 and ventricular tachycardia in 1. Univariate analysis reveals structural heart disease, ECG abnormalities and LVEF associated with the risk of significant cardiac rhythmic events defined by the combined end-point. Multivariate analysis using a Cox model found that the only independent predictor of events was an ECG abnormality. The long-term risk of significant event in the subset with ECG abnormalities is of 10.6% (12/113). If unexplained syncope recurrence was included in the combined end-point, ECG abnormality and LVEF were both determinants with a 13.3% (15/113) risk of a arrhythmic events analysis in the subset of patients presenting with ECG abnormalities and Cox model found ECG abnormality as the only independent predictor of event. Conclusions This study demonstrated that an ECG abnormality is the only predictive variable associated with a significant arrhythmic event in patients with a lone episode of syncope or near syncope and a negative EPS.

Background— Cavotricuspid isthmus (CTI) characteristics are rarely documented when comparing catheters in radiofrequency ablation (RFA) of atrial flutter (AFL). Our objectives were (1) to evaluate the impact of CTI morphology and length on ablation procedures and (2) to compare the efficacy of an 8-mm-tip catheter with an irrigated cooled-tip RFA in the subgroup presumed to be more difficult to treat (with a long CTI, >35 mm). Methods and Results— Over a period of 17 months, 185 patients accepted the protocol and underwent an isthmogram in preparation for RFA. Groups were classified according to CTI length and CTI morphology. RFA was performed with an 8-mm-tip catheter for patients with a short CTI, ≤35 mm (n=123), whereas randomization between an 8-mm-tip and a cooled-tip catheter applied to patients with a longer CTI, >35 mm (n=62). For long CTI, 32 patients were assigned to an 8-mm catheter and 30 patients to the cooled-tip RFA ablation group. In this subset, RF application (18.2±17 versus 19±13 minutes) and x-ray exposure (20.8±18 versus 18±13 minutes) did not differ between the 8-mm-tip and the cooled-tip procedures. Number of applications (9.9±11 versus 18.6±15 minutes; P P =0.0001) differed significantly between patients with short and long CTIs. Patients with short and straight CTIs required 3 times fewer RFA applications and shorter x-ray exposure compared with other CTI morphologies (pouch-like recesses and concave characteristics). Conclusions— The number of RF applications required for a complete isthmus block in long CTIs is not influenced by the choice between an 8-mm or cooled-tip catheter. Procedure parameters, however, are significantly influenced by CTI length and morphology. Pouch-like recesses and concave characteristics account for much longer ablation times at all CTI lengths.

Aim Assessment of a bidirectional conduction block within the cavotricuspid isthmus (CTI) is critical during radiofrequency (RF) atrial flutter (AF) ablation. We investigated the use of bipolar atrial electrogram (BAE) morphology as an additional criterion identifying CTI block and tested it against two recognized criteria: differential pacing and reversal of the right atrial depolarization sequence during coronary sinus (CS) pacing. Methods and results An RF ablation procedure was performed during 600 ms CS pacing in 100 consecutive patients with a common AF. BAE recorded along the CTI were continuously monitored. CTI conduction block was achieved by RF ablation in all patients and a clear change in BAE polarity in the Electrogram recorded by the dipoles located on the CTI and immediately lateral to the intended line of block (RS to QR pattern) associated with a confirmed CTI conduction block was observed in all cases. BAE morphology changes predicted bidirectional CTI conduction blocks with a 100% positive and a 100% negative predictive value. At a mean follow-up of 33 11 months, there was a 5% AF recurrence rate. Conclusions Our study suggests that morphological changes in BAE recorded at sites lateral and adjacent to the target line of block may be used as a unique and robust criterion to validate CTI conduction block during AF ablation procedure.

This case report describes a 68-year-old woman presenting with flecainide induced syncope due to torsades de pointes (TP) ventricular tachycardia. Before TP onset, the QTc interval reached 680 ms without changes in QRS duration. None of the usual triggers were found. Prolongation of QT under flecainide is exceptional and the occurrence of TP without concurrent triggers has not been reported in the literature.

Background The occurrence of early atrial fibrillation (≤6 months) after ablation of common atrial flutter is of clinical significance. Variables predicting this evolution in ablated patients without a previous atrial fibrillation history have not been fully investigated. Objectives The aim of the present study was: (1) to identify predictive factors of early atrial fibrillation (≤6 months) in the overall population following atrial flutter catheter ablation; (2) to identify predictive variables of early atrial fibrillation following (≤6 months) atrial flutter catheter ablation within a subgroup of patients without documented prior atrial fibrillation. Methods This study prospectively included 96 consecutive patients (age 65±13 years; 18 women) over a 12-month period. Their counterclockwise flutter was ablated by radiofrequency, by the same operator, with an 8-mm-tip catheter. Clinical, electrophysiological and echocardiographic data were collected and 27 variables were retained for analysis: age; gender; type of atrial flutter (permanent vs paroxysmal); symptom duration (months±SD); pre-ablation history of atrial fibrillation; structural heart disease; left ventricular ejection fraction (%); left atrial size (mm); cava–tricuspid isthmus dimension; septal isthmus dimension; systolic pulmonary pressure > or ≤30mmHg; right atrial area; left atrial area; isthmus block; number of radiofrequency applications (±SD); antiarrhythmic drugs at discharge; left ventricular diastolic diameter; left ventricular systolic diameter; left ventricular telediastolic volume; left ventricular telesystolic volume; A-wave velocity (cm.s−1); E-wave velocity (cm.s−1); E/A; isovolumetric relaxation time; E-wave deceleration time; significant mitral regurgitation and flutter cycle length (ms). Results Of the 96 consecutive ablated patients, early atrial fibrillation was documented in 16 patients (17%). Atrial fibrillation occurred 30±46 days (range 1 to 171 days) after ablation. Univariate analysis associated an early occurrence of atrial fibrillation with: atrial fibrillation history, left ventricular ejection fraction, left atrial size, left ventricular telesystolic volume, A-wave velocity, significant mitral regurgitation and flutter cycle length. Multivariate analysis using a Cox model found that the only independent predictors of early atrial fibrillation were left ventricular ejection fraction and pre-ablation history of atrial fibrillation. In the subgroup without prior atrial fibrillation history (n=63; 66%), the only independent predictor of early atrial fibrillation was the presence of a significant mitral regurgitation. Conclusions In a subgroup of patients without atrial fibrillation history, 8% of patients revealed an early atrial fibrillation. Mitral regurgitation is a strong predictive factor of early atrial fibrillation occurrence with 80% sensitivity, 78% specificity and 98% negative predictive value. These data should be considered in post-ablation management.

The cephalic vein (CV) is preferable to the subclavian vein for implanting permanent pacing leads because of fewer complications. Unfortunately, this access is unusable in a substantial number of patients. This prospective study evaluates a technique to increase CV access for the placement of two silicons bipolar leads used in DDD pulse generator implants. A standard cephalic cutdown was performed under local anesthesia and a hydrophilic guidewire (HGW) threaded in the CV. The first (ventricular) bipolar lead was then introduced and positioned. When possible, introduction of the second (atrial) lead followed the same direct access. A failed introduction led to a modified procedure (MP) relying on a “split” introducer (8–9 Fr Plastimed) advanced with a circular motion over the HGW, then removal of the dilator, removal of the HGW, insertion of the pacing lead into the sheath with placement in the right atrium, followed by sheath withdrawal. Over an 18-month period, 90 consecutive patients had DDD pacemakers implanted. The CV was accessible in 76 (84.5%) of 90 patients and the direct introduction of the ventricular lead was obtained in 74 (97.4%) of these. Atrialization proceeded as follows: direct access CV in 14 (18%) of 76 patients, MP access in 54 (71 %) of 76 patients, and MP failure in 8(11 %) of 76 patients. Overall, this approach allowed cephalic dual insertion in 68 (89%) of 76 patients. In conclusion, the modified procedure presented in this study allows a dual catheteriza-tion with bipolar leads in 89% of patients when a CV is available. This significantly improves the success rate for dual bipolar lead implants in this configuration.

Background —We sought to compare published methods to an alternative approach ascertaining cavotricuspid isthmus (CTI) block during atrial flutter ablation. Methods and Results —In 39 consecutive patients who underwent an atrial flutter ablation procedure, a 24-pole mapping catheter was positioned so that 2 adjacent dipoles were bracketing the targeted CTI line of block (LOB), with proximal dipoles lateral to the LOB and distal dipoles in the coronary sinus. Two pacing sites were lateral (positions A and B) and 2 were septal (positions C and D) to the LOB, with locations A and D closest to the LOB. A resulting CTI block was accepted when 3 criteria were fulfilled: (1) complete reversal of the right atrial depolarization on the 24-pole catheter when pacing in the coronary sinus, (2) conduction delays from A to D greater than from B to D, and (3) conduction delays from D to A greater than from C to A. A successful CTI block was obtained in all patients. Before CTI block was obtained, a progressive CTI conduction delay was observed in 11 patients (28.2%). During the procedure, the 3 criteria defined above were either all present or all absent. Conclusions —This study establishes that reversal of the atrial depolarization sequence up to the LOB is a definitive and mandatory criteria of successful atrial flutter ablation.

Objectives: This study documents biological (haematocrit variations) and therapeutic parameters (salbutamol doses, volumes perfused) in two groups tocolysed with salbutamol, one with and the other without APO in order to define the risk factors linked to APO and to establish a standard protocol of management. Study design: This retrospective study includes data from 68 intravenous salbutamol tocolysis with four resulting APOs, carried out between January 1st, 1993 and December 31st, 1995. Results: There was an excessive level of salbutamol administered over 48 h in the complicated APO-group (122.5±52 mg) opposed to the non-APO group (44.9±21 mg) as well as an overload of perfused solute (3.1±1.1 l) versus (1.9±1.1 l). Blood hemodilution was demonstrated in the APO group with a decrease of haematocrit by over 10% between the admission and the control value. No other risk factor was found. Conclusion: Tocolysis should be administered at the lowest possible perfusion rate with incremental doses as long as the heart rate stays under 120 beats/min and stopped after 48 h. Administration of maximal 1 l of solute perfused/day is recommended. For the patient's follow-up we estimate daily input and output fluid to avoid hydric overload, and a daily control of haematocrit whose variation must be less than 10%.