Real-world assessment of multipolar and point-by-point mapping for premature ventricular contraction ablation.

AIMS: We aimed to assess the acute and midterm efficacy of premature ventricular contraction (PVC) ablation guided by multielectrode and point-by-point (PbP) mapping. METHODS AND RESULTS: This is a retrospective, international multicentre study of consecutive patients referred for PVC ablation in 10 hospital centres from January 2017 to December 2021. Based on the mapping approach, two cohorts were identified: the 'Multipolar group', where a dedicated high-density mapping catheter was employed, and the 'PbP group', where mapping was performed with the ablation catheter. Procedural endpoints, safety, and acute (procedural) and midterm efficacies were assessed. Of the 698 patients included in this study, 592 received activation mapping [46% males, median age of 55 (41-65) years]-248 patients in the Multipolar group and 344 patients in the PbP group. A higher number of activation points [432 (217-843) vs. 95 (42-185), P < 0.001], reduced mapping time (40 ± 38 vs. 61 ± 50 min, P < 0.001), and shorter procedure time (124 ± 60 vs. 143 ± 63 min, P < 0.001) were reported in the Multipolar group. Both groups had high acute success rates (84.7% with Multipolar mapping vs. 81.3% with PbP mapping, P = 0.63), as well as midterm efficacy (83.4% vs. 77.4%, P = 0.08), with no significant differences in the risk of adverse events (6.0% vs. 3.5%, P = 0.24). However, for left-sided PVC ablation specifically, there was a higher midterm efficacy in the Multipolar group (80.7% vs. 69.5%, P = 0.04), with multipolar mapping being an independent predictor of success [adjusted OR = 2.231 (95% CI, 1.476-5.108), P = 0.02]. CONCLUSION: The acute and midterm efficacies of PVC ablation are high with both multipolar and PbP mapping, although the former allows for quicker procedures and may potentially improve the outcomes of left-sided PVC ablation.

Pulmonary vein isolation alone or in combination with substrate modulation after electrical cardioversion failure in patients with persistent atrial fibrillation: The PACIFIC trial: Study design.

INTRODUCTION: Pulmonary vein isolation (PVI) is effective at treating 50% of unselected patients with persistent atrial fibrillation (AF). Alternatively, PVI combined with a new ablation strategy entitled the Marshall-PLAN ensures a 78% 1-year sinus rhythm (SR) maintenance rate in the same population. However, a substantial subset of patients could undergo the Marshall-PLAN unnecessarily. It is therefore essential to identify those patients who can be treated with PVI alone versus those who may truly benefit from the Marshall-PLAN before ablation is performed. In this context, we hypothesized that electrical cardioversion (EC) could help to select the most appropriate strategy for each patient. METHODS: In this multicentre, prospective, randomized study, patients with AF recurrence within 4 weeks after EC will be randomized 1:1 to PVI alone or the Marshall-PLAN. Conversely, patients in whom SR is maintained for ≥4 weeks after EC will be treated with PVI only and included in a prospective registry. The primary endpoint will be the 1-year SR maintenance rate after a single ablation procedure. RESULTS AND CONCLUSION: The Marshall-PLAN might be necessary in patients with an advanced degree of persistent AF (i.e., where SR is not maintained for ≥4 uninterrupted weeks after EC). Conversely, in patients with mild or moderate persistent AF (i.e., where SR is maintained for ≥4 weeks after EC), PVI alone might be a sufficient ablation strategy. The PACIFIC trial is the first study designed to assess whether rhythm monitoring after EC could help to identify patients who should undergo adjunctive ablation strategies beyond PVI.

Ostial vs. wide area circumferential ablation guided by the Ablation Index in paroxysmal atrial fibrillation.

AIMS: Pulmonary vein isolation (PVI) guided by the Ablation Index (AI) has shown high acute and mid-term efficacy in the treatment of paroxysmal atrial fibrillation (AF). Previous data before the AI-era had suggested that wide-area circumferential ablation (WACA) was preferable to ostial ablation. However, with the use of AI, we hypothesize that ostial circumferential ablation is non-inferior to WACA and can improve outcomes in paroxysmal AF. METHODS AND RESULTS: Prospective, multicentre, non-randomized, non-inferiority study of consecutive patients were referred for paroxysmal AF ablation from January 2020 to September 2021. All procedures were performed using the AI software, and patients were separated into two different groups: WACA vs. ostial circumferential ablation. Acute reconnection, procedural data, and 1-year arrhythmia recurrence were assessed. During the enrolment period, 162 patients (64% males, mean age of 60 ± 11 years) fulfilled the study inclusion criteria-81 patients [304 pulmonary vein (PV)] in the WACA group and 81 patients (301 PV) in the ostial group. Acute PV reconnection was identified in 7.9% [95% confidence interval (CI), 4.9-11.1%] of PVs in the WACA group compared with 3.3% (95% CI, 1.8-6.1%) of PVs in the ostial group [P < 0.001 for non-inferiority; adjusted odds ratio 0.51 (95% CI, 0.23-0.83), P = 0.05]. Patients in the WACA group had longer ablation (35 vs. 29 min, P = 0.001) and procedure (121 vs. 102 min, P < 0.001) times. No significant difference in arrhythmia recurrence was seen at 1-year of follow-up [11.1% in WACA vs. 9.9% in ostial, hazard ratio 1.13 (95% CI, 0.44-1.94), P = 0.80 for superiority]. CONCLUSION: In paroxysmal AF patients treated with tailored AI-guided PVI, ostial circumferential ablation is not inferior to WACA with regard to acute PV reconnection, while allowing quicker procedures with less ablation time.

Assessment of the need of a waiting period after pulmonary vein isolation with the ablation index software.

PURPOSE: Since the widespread availability of contact-force sensing catheters, the need for a waiting period after pulmonary vein isolation (PVI) has not been reassessed. We aim to evaluate whether a waiting period is still necessary after PVI guided by the ablation Index (AI). METHODS: Prospective, multicenter, randomized study of consecutive patients referred for paroxysmal atrial fibrillation (AF) ablation from May 2019 to February 2020. Patients were randomized in a 1:1 ratio to PVI with versus without a waiting period of 20 min. Acute pulmonary vein (PV) reconnection after adenosine challenge was the primary endpoint. A per-protocol analysis was designed to determine whether a strategy of dismissing the waiting period after PVI was noninferior to waiting for 20 min for identifying acute PV reconnection. PVI was guided by tailored AI values and an interlesion distance ≤6 mm. RESULTS: During the enrollment period, 167 patients (56% males, mean age of 57 ± 14 years) fulfilled the study inclusion criteria - 84 patients (308 PV) in the waiting period group (Group A) and 83 patients (314 PV) in the group without a waiting period (Group B). Acute PV reconnection was identified in 3.8% (95% confidence interval [CI], 1.7%-5.9%) of PVs in the study group B compared to 2.9% (95% CI, 1.0%-4.8%) of PVs in the Group A (p = .002 for non-inferiority). At 1-year follow-up, there was no significant difference in arrhythmia recurrence between groups (9.5% in Group A vs. 9.6% in Group B, hazard ratio: 1.03 [95% CI, 0.39-2.73], p = .98). CONCLUSION: In paroxysmal AF patients submitted to ablation, a tailored PVI guided by the AI rendered a 20-min waiting period unnecessary.

Long-Term Follow-Up of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator: The DAI-T4F Nationwide Registry.

BACKGROUND: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, and sudden cardiac death represents an important mode of death in these patients. Data evaluating the implantable cardioverter defibrillator (ICD) in this patient population remain scarce. METHODS: A Nationwide French Registry including all patients with tetralogy of Fallot with an ICD was initiated in 2010 by the French Institute of Health and Medical Research. The primary time to event end point was the time from ICD implantation to first appropriate ICD therapy. Secondary outcomes included ICD-related complications, heart transplantation, and death. Clinical events were centrally adjudicated by a blinded committee. RESULTS: A total of 165 patients (mean age, 42.2±13.3 years, 70.1% males) were included from 40 centers, including 104 (63.0%) in secondary prevention. During a median (interquartile range) follow-up of 6.8 (2.5-11.4) years, 78 (47.3%) patients received at least 1 appropriate ICD therapy. The annual incidence of the primary outcome was 10.5% (7.1% and 12.5% in primary and secondary prevention, respectively; P=0.03). Overall, 71 (43.0%) patients presented with at least 1 ICD complication, including inappropriate shocks in 42 (25.5%) patients and lead dysfunction in 36 (21.8%) patients. Among 61 (37.0%) patients in primary prevention, the annual rate of appropriate ICD therapies was 4.1%, 5.3%, 9.5%, and 13.3% in patients with, respectively, 0, 1, 2, or ≥3 guidelines-recommended risk factors. QRS fragmentation was the only independent predictor of appropriate ICD therapies (hazard ratio, 3.47 [95% CI, 1.19-10.11]), and its integration in a model with current criteria increased the 5-year time-dependent area under the curve from 0.68 to 0.81 (P=0.006). Patients with congestive heart failure or reduced left ventricular ejection fraction had a higher risk of nonarrhythmic death or heart transplantation (hazard ratio, 11.01 [95% CI, 2.96-40.95]). CONCLUSIONS: Patients with tetralogy of Fallot and an ICD experience high rates of appropriate therapies, including those implanted in primary prevention. The considerable long-term burden of ICD-related complications, however, underlines the need for careful candidate selection. A combination of easy-to-use criteria including QRS fragmentation might improve risk stratification. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03837574.

High-power short-duration versus low-power long-duration ablation guided by the ablation index.

AIMS: To compare the two different ablation strategies, both guided by the Ablation Index (AI), in the setting of atrial fibrillation (AF) ablation: high-power short-duration (HPSD) ablation using 40 W on the posterior wall and 50 W elsewhere versus low-power long-duration (LPLD) using 25 W posteriorly and 35 W elsewhere. METHODS: Prospective, multicenter nonrandomized, noninferiority study of consecutive patients referred for paroxysmal AF ablation from January 2018 to July 2019. Ablation was guided by the AI (≥500 for anterior segments, ≥450 for the roof and inferior segments and 400 posteriorly) and an interlesion distance (ILD) ≤ 6 mm. Patients were separated into two groups: HPSD vs LPLD. Acute reconnection (after adenosine trial) and 2-year outcomes were assessed. RESULTS: 160 patients (61% males, median age of 62 [IQR 51-69] years), fulfilled the study inclusion criteria - 80 patients (316 pulmonary veins [PV]) in the HPSD group and 80 patients (314 PV) in the LPLD. The probability of acute PV reconnection was similar between both groups: 2.2% in HPSD, 95%CI 0.6% to 3.8% vs. 3.4% in LPLD, 95%CI 1.4% to 5.4%; p < 0.001 for noninferiority. Median PV ablation time (20 min vs 30 min, p < 0.01) and procedure duration (80 min vs 100 min, p < 0.001) were shorter in the HPSD group. After a median follow-up of 26 months, arrhythmia recurrence was similar between groups (17.5% in HPSD group vs. 18.8% in LPLD group, p = 0.79). CONCLUSIONS: In paroxysmal AF patients treated with the Ablation Index, a HPSD strategy is noninferior to the more standard LPLD ablation, while allowing for quicker procedures with shorter ablation times.

Multielectrode mapping for premature ventricular contraction ablation - A prospective, multicenter study.

PURPOSE: We aim to evaluate whether the use of a multielectrode mapping catheter could lead to higher efficacy of premature ventricular contraction (PVC) ablation. METHODS: Prospective, multicenter nonrandomized study of consecutive patients referred for PVC ablation from January 2018 to June 2021. Patients were separated into two groups: activation map performed with the PentaRay catheter (Study group) or with the ablation catheter (Control group). PMF software was used in both groups. Procedural endpoints and 1-year freedom from ventricular arrhythmia were assessed. RESULTS: During the enrollment period 136 patients (60% males, mean age of 55 ± 17 years, 60% left-sided origin) fulfilled the inclusion criteria - 68 patients in each group. Patients in the Study Group had a sevenfold higher number of acquired activation points (768 ± 728 vs. 110 ± 79, p < 0.01), a shorter mapping time (28 ± 19 min vs. 49 ± 32 min, p < 0.01) and a quicker procedure time (110 ± 33 min vs. 134 ± 50 min, p < 0.01), compared to patients in the Control Group. While there were no significant differences in the acute success (95.6% in the Study Group vs. 90.1% in Control group, p = 0.49), or adverse events (4% in the Study group vs. 7% in the Control group, p = 0.72), patients in the Study group had a higher freedom from ventricular arrhythmia at 1-year (89.7% vs. 70.6%, p = 0.01). The use of the PentaRay catheter was an independent predictor of success (HR = 6.20 [95% CI, 1.08-35.47], p = 0.003). CONCLUSIONS: The use of the PentaRay catheter may improve the outcome of PVC ablation while reducing procedure time.

Recurrences of Atrial Fibrillation Despite Durable Pulmonary Vein Isolation: The PARTY-PVI Study.

BACKGROUND: Recurrences of atrial fibrillation (AF) after pulmonary vein isolation (PVI) are mainly due to pulmonary vein reconnection. However, a growing number of patients have AF recurrences despite durable PVI. The optimal ablative strategy for these patients is unknown. We analyzed the impact of current ablation strategies in a large multicenter study. METHODS: Patients undergoing a redo ablation for AF and presenting durable PVI were included. The freedom from atrial arrhythmia after pulmonary vein-based, linear-based, electrogram-based, and trigger-based ablation strategies were compared. RESULTS: Between 2010 and 2020, 367 patients (67% men, 63±10 years, 44% paroxysmal) underwent a redo ablation for AF recurrences despite durable PVI at 39 centers. After durable PVI was confirmed, linear-based ablation was performed in 219 (60%) patients, electrogram-based ablation in 168 (45%) patients, trigger-based ablation in 101 (27%) patients, and pulmonary vein-based ablation in 56 (15%) patients. Seven patients (2%) did not undergo any additional ablation during the redo procedure. After 22±19 months of follow-up, 122 (33%) and 159 (43%) patients had a recurrence of atrial arrhythmia at 12 and 24 months, respectively. No significant difference in arrhythmia-free survival was observed between the different ablation strategies. Left atrial dilatation was the only independent factor associated with arrhythmia-free survival (HR, 1.59 [95% CI, 1.13-2.23]; P=0.006). CONCLUSIONS: In patients with recurrent AF despite durable PVI, no ablation strategy used alone or in combination during the redo procedure appears to be superior in improving arrhythmia-free survival. Left atrial size is a significant predictor of ablation outcome in this population.

Rapid ventricular tachycardia in patients with tetralogy of Fallot and implantable cardioverter-defibrillator: Insights from the DAI-T4F nationwide registry.

BACKGROUND: In repaired tetralogy of Fallot (TOF), little is known about characteristics of patients with rapid ventricular tachycardia (VT). Also, whether patients with a first episode of nonrapid VT may subsequently develop rapid VT or ventricular fibrillation (VF) has not been addressed. OBJECTIVES: The objectives of this study were to compare patients with rapid VT/VF with those with nonrapid VT and to assess the evolution of VT cycle lengths (VTCLs) overtime. METHODS: Data were analyzed from a nationwide registry including all patients with TOF and implantable cardioverter-defibrillator (ICD) since 2000. Patients with ≥1 VT episode with VTCL ≤250 ms (240 beats/min) formed the rapid VT/VF group. RESULTS: Of 144 patients (mean age 42.0 ± 12.7 years; 104 [72%] men), 61 (42%) had at least 1 VT/VF episode, including 28 patients with rapid VT/VF (46%), during a median follow-up of 6.3 years (interquartile range 2.2-10.3 years). Compared with patients in the nonrapid VT group, those in the rapid VT/VF group were significantly younger at ICD implantation (35.2 ± 12.6 years vs 41.5 ± 11.2 years; P = .04), had more frequently a history of cardiac arrest (8 [29%] vs 2 [6%]; P = .02), less frequently a history of atrial arrhythmia (11 [42%] vs 22 [69%]; P = .004), and higher right ventricular ejection fraction (43.3% ± 10.3% vs 36.6% ± 11.2%; P = .04). The median VTCL of VT/VF episodes was 325 ms (interquartile range 235-429 ms). None of the patients with a first documented nonrapid VT episode had rapid VT/VF during follow-up. CONCLUSION: Patients with TOF and rapid VT/VF had distinct clinical characteristics. The relatively low variation of VTCL over time suggests a room for catheter ablation without a backup ICD in selected patients with well-tolerated VT.

Optimizing pacemaker longevity with pacing mode and settings programming: results from a pacemaker multicenter registry.

BACKGROUND: This study aimed to describe the influence on dual-chamber devices' expected longevity of devices' settings. METHODS: Data from patients implanted with dual chamber devices (Symphony™, SORIN CRM SAS, Clamart, France) from 2003 to 2006 were collected in registries. Programmer files were retrieved: device-estimated longevity, assessed through algorithm prediction, was analyzed according to device settings. RESULTS: One thousand sixty-eight recipients of dual chamber pacemaker in sinus rhythm (75.3±11.1 years, 54.5% male, ventricular block 30%, brady-tachy syndrome 21%, and sinus node dysfunction 49%) were followed up to 14.2±12.1 months (ranging from first quartile Q1: 2.9 months to fourth quartile Q4: 49.3 months) after implantation. DDD with automatic mode conversion and minimized ventricular pacing (SafeR) modes were programmed in 34.3%, 2.9%, and 62.8% of the patients, respectively. The mean total longevity estimated by the device was 134.1±31.5 months (11.2±2.6 years). Significant increase in longevity was observed in devices undergoing at least one reprogramming (134.4±31.4 months) versus device presenting no reprogramming (103.4±32.3 months, P=0.0005). The parameters associated with the major increase in mean longevity were the mode (mean longevity increase of +23.9 months in SafeR as compared to DDD mode, P<0.0001) and the atrial (A) and ventricular (V) amplitudes (mean longevity increase of +29.6 and +26.9 months for a decrease of less than 1V in A and V outputs respectively, P<0.0001). CONCLUSION: This study provides information on dual chamber pacemakers' longevity and highlights the impact of devices' reprogramming on expected longevities.

Two years after pulmonary vein isolation guided by ablation index-a multicenter study.

Background: The use of the Ablation Index (AI) software for paroxysmal atrial fibrillation (AF) has been associated with higher acute effectiveness and higher 1-year arrhythmia freedom. There is, however, a lack of data concerning longer follow-up. We aim to evaluate the 2-year outcomes after a standardized AI-guided pulmonary vein isolation (PVI). Methods: Prospective, multicenter study of consecutive patients referred for paroxysmal AF ablation from January 2018 to July 2019. PVI was guided by a tailored AI value (≥500 for anterior segment, ≥450 for the roof segments and inferior segments, and 400 for the posterior wall) and an ILD ≤6 mm. The primary endpoints were acute and long-term effectiveness. Results: The study included 218 (842 PV) patients (61% males, median age of 60 [IQR 49-68] years) with paroxysmal AF. First-pass isolation was obtained in 93% of the patients, with an acute reconnection occurring in 10.6% of the patients (3.2% of the PV) following adenosine trial. After a median follow-up of 26 (IQR 20-30) months, freedom from any documented atrial arrhythmia was 83.4%, off-AAD. The rate of adverse events was 1.4%. Although procedural parameters differ across centers (p < 0.001), the acute (p = 0.56) and long-term effectiveness (p = 0.83) were consistent between centers. Conclusions: Patients with paroxysmal AF submitted to an AI-guided PVI workflow presented high arrhythmia freedom at 2-years of follow-up.

Sex Differences in Outcomes of Tetralogy of Fallot Patients With Implantable Cardioverter-Defibrillators.

BACKGROUND: Women with congenital heart disease at high risk for sudden cardiac death have been poorly studied thus far. OBJECTIVES: The aim of this study was to assess sex-related differences in patients with tetralogy of Fallot (TOF) and implantable cardioverter-defibrillators (ICDs). METHODS: Data were analyzed from the DAI-T4F (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator) cohort study, which has prospectively enrolled all patients with TOF with ICDs in France since 2010. Clinical events were centrally adjudicated by a blinded committee. RESULTS: A total of 165 patients (mean age 42.2 ± 13.3 years) were enrolled from 40 centers, including 49 women (29.7%). Among the 9,692 patients with TOF recorded in the national database, the proportion of women with ICDs was estimated to be 1.1% (95% CI: 0.8%-1.5%) vs 2.2% (95% CI: 1.8%-2.6%) in men (P < 0.001). The clinical profiles of patients at implantation, including the number of risk factors for ventricular arrhythmias, were similar between women and men. During a median follow-up period of 6.8 years (IQR: 2.5-11.4 years), 78 patients (47.3%) received at least 1 appropriate ICD therapy, without significant difference in annual incidences between women (12.1%) and men (9.9%) (HR: 1.22; 95% CI: 0.76-1.97; P = 0.40). The risk for overall ICD-related complications was similar in women and men (HR: 1.33; 95% CI: 0.81-2.19; P = 0.30), with 24 women (49.0%) experiencing at least 1 complication. CONCLUSIONS: Our findings suggest that women with TOF at high risk for sudden cardiac death have similar benefit/risk balance from ICD therapy compared with men. Whether ICD therapy is equally offered to at-risk women vs men warrants further evaluation in TOF as well as in other congenital heart disease populations. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator [DAI-T4F]; NCT03837574).

IP-10 response to RD1 antigens might be a useful biomarker for monitoring tuberculosis therapy.

BACKGROUND: There is an urgent need of prognosis markers for tuberculosis (TB) to improve treatment strategies. The results of several studies show that the Interferon (IFN)-γ-specific response to the TB antigens of the QuantiFERON TB Gold (QFT-IT antigens) decreases after successful TB therapy. The objective of this study was to evaluate whether there are factors other than IFN-γ [such as IFN-γ inducible protein (IP)-10 which has also been associated with TB] in response to QFT-IT antigens that can be used as biomarkers for monitoring TB treatment. METHODS: In this exploratory study we assessed the changes in IP-10 secretion in response to QFT-IT antigens and RD1 peptides selected by computational analysis in 17 patients with active TB at the time of diagnosis and after 6 months of treatment. The IFN-γ response to QFT-IT antigens and RD1 selected peptides was evaluated as a control. A non-parametric Wilcoxon signed-rank test for paired comparisons was used to compare the continuous variables at the time of diagnosis and at therapy completion. A Chi-square test was used to compare proportions. RESULTS: We did not observe significant IP-10 changes in whole blood from either NIL or QFT-IT antigen tubes, after 1-day stimulation, between baseline and therapy completion (p = 0.08 and p = 0.7 respectively). Conversely, the level of IP-10 release to RD1 selected peptides was significantly different (p = 0.006). Similar results were obtained when we detected the IFN-γ in response to the QFT-IT antigens (p = 0.06) and RD1 selected peptides (p = 0.0003). The proportion of the IP-10 responders to the QFT-IT antigens did not significantly change between baseline and therapy completion (p = 0.6), whereas it significantly changed in response to RD1 selected peptides (p = 0.002). The proportion of IFN-γ responders between baseline and therapy completion was not significant for QFT-IT antigens (p = 0.2), whereas it was significant for the RD1 selected peptides (p = 0.002), confirming previous observations. CONCLUSIONS: Our preliminary study provides an interesting hypothesis: IP-10 response to RD1 selected peptides (similar to IFN-γ) might be a useful biomarker for monitoring therapy efficacy in patients with active TB. However, further studies in larger cohorts are needed to confirm the consistency of these study results.

Impact of Pulmonary Valve Replacement on Ventricular Arrhythmias in Patients With Tetralogy of Fallot and Implantable Cardioverter-Defibrillator.

OBJECTIVES: This study aimed to assess the impact of pulmonary valve replacement (PVR) on ventricular arrhythmias burden in a population of tetralogy of Fallot (TOF) patients with continuous cardiac monitoring by implantable cardioverter-defibrillators (ICDs). BACKGROUND: Sudden cardiac death is a major cause of death in TOF, and right ventricular overload is commonly considered to be a potential trigger for ventricular arrhythmias. METHODS: Data were analyzed from a nationwide French ongoing study (DAI-T4F) including all TOF patients with an ICD since 2000. Survival data with recurrent events were used to compare the burden of appropriate ICD therapies before and after PVR in patients who underwent PVR over the study period. RESULTS: A total of 165 patients (mean age 42.2 ± 13.3 years, 70.1% male) were included from 40 centers. Over a median follow-up period of 6.8 (interquartile range: 2.5 to 11.4) years, 26 patients (15.8%) underwent PVR. Among those patients, 18 (69.2%) experienced at least 1 appropriate ICD therapy. When considering all ICD therapies delivered before (n = 62) and after (n = 16) PVR, the burden of appropriate ICD therapies was significantly lower after PVR (HR: 0.21; 95% confidence interval [CI]: 0.08 to 0.56; p = 0.002). Respective appropriate ICD therapies rates per 100 person-years were 44.0 (95% CI: 35.7 to 52.5) before and 13.2 (95% CI: 7.7 to 20.5) after PVR (p < 0.001). In the overall cohort, PVR before ICD implantation was also independently associated with a lower risk of appropriate ICD therapy in primary prevention patients (HR: 0.29 [95% CI: 0.10 to 0.89]; p = 0.031). CONCLUSIONS: In this cohort of high-risk TOF patients implanted with an ICD, the burden of appropriate ICD therapies was significantly reduced after PVR. While optimal indications and timing for PVR are debated, these findings suggest the importance of considering ventricular arrhythmias in the overall decision-making process. (French National Registry of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator [DAI-T4F]; NCT03837574).

DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells.

Early interactions between lung dendritic cells (LDCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, are thought to be critical for mounting a protective anti-mycobacterial immune response and for determining the outcome of infection. However, these interactions are poorly understood, at least at the molecular level. Here we show that M. tuberculosis enters human monocyte-derived DCs after binding to the recently identified lectin DC-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN). By contrast, complement receptor (CR)3 and mannose receptor (MR), which are the main M. tuberculosis receptors on macrophages (Mphis), appeared to play a minor role, if any, in mycobacterial binding to DCs. The mycobacteria-specific lipoglycan lipoarabinomannan (LAM) was identified as a key ligand of DC-SIGN. Freshly isolated human LDCs were found to express DC-SIGN, and M. tuberculosis-derived material was detected in CD14(-)HLA-DR(+)DC-SIGN(+) cells in lymph nodes (LNs) from patients with tuberculosis. Thus, as for human immunodeficiency virus (HIV), which is captured by the same receptor, DC-SIGN-mediated entry of M. tuberculosis in DCs in vivo is likely to influence bacterial persistence and host immunity.

Synthesis and superconducting properties of CaC6.

Among the superconducting graphite intercalation compounds, CaC6 exhibits the highest critical temperature Tc=11.5 K. Bulk samples of CaC6 are obtained by immersing highly oriented pyrographite pieces in a well-chosen liquid Li-Ca alloy for 10 days at 350 °C. The crystal structure of CaC6 belongs to the [Formula: see text] space group. In order to study the superconducting properties of CaC6, magnetisation was measured as a function of temperature and direction of magnetic field applied parallel or perpendicular to the c-axis. Meissner effect was evidenced, as well as a type II superconducting behaviour and a small anisotropy. In agreement with calculations, experimental results obtained from various techniques suggest that a classical electron-phonon mechanism is responsible for the superconductivity of CaC6. Application of high pressure increases the Tc up to 15.1 K at 8 GPa.

B-cell immune responses in HIV positive and HIV negative patients with tuberculosis evaluated with an ELISA using a glycolipid antigen.

The diagnostic value of the PGL-Tb1 enzyme-linked immunosorbent assays (ELISA) was established following a survey study using sera from 220 Tuberculosis patients (including 69 HIV coinfected) and 324 controls. A higher percentage (76.8%) of the HIV-seropositive compared to the HIV-seronegative (58.9%) TB patients were ELISA positive (p=0.02) with a specificity of 94%. In HIV-positive TB patients, ELISA sensitivity was identical for all sites of disease and antibody levels were not affected by the CD4+ counts, PPD results, age or bacterial yield. Combining data for both the smear microscopy and ELISA maximized sensitivity. The kinetics of anti-PGL-Tb1 antibody was evaluated in cohort studies using sera collected before, during and after treatment for clinical TB for 79 TB patients (including 39 HIV coinfected). Statistically significant ELISA signals were observed in 51.3% of HIV-seropositive TB patients prior to the diagnosis of clinical TB and elevated antibody levels persisting 18 months after the end of antituberculous chemotherapy. Asymptomatic development of antibody also occurred in 22.7% of a cohort of 44 HIV-positive patients with a high risk of tuberculosis, but no correlation was found between persisting elevated antibody levels and progression to active disease. This antibody response in absence of disease, might reflect the control of an incipient tuberculosis infection by antituberculous prophylaxis or through an improved protective immune response associated with antiretroviral therapy.

Elimination of the negative component of the unipolar electrogram as a local procedural endpoint during paroxysmal atrial fibrillation catheter ablation using contact-force sensing: the UNIFORCE study.

PURPOSE: Elimination of the negative component of the unipolar atrial electrogram is a reliable indicator of the creation of a transmural lesion. Contact-force (CF) sensing technology has the potential to increase the durability of pulmonary vein isolation (PVI). In the present multicenter study, we assessed the 2-year sinus rhythm (SR) maintenance rate in patients with paroxysmal atrial fibrillation (PAF) after PVI guided by these two approaches. METHODS: Two hundred fifteen consecutive PAF patients (62.1 ± 10.1 years, 65 women) were prospectively enrolled. All patients underwent PVI under CARTO guidance according to a systematic contiguous "point-by-point" approach, using radiofrequency energy, and a CF externally irrigated ablation catheter with the goal of at least 10g (ideally 20g) of force. The ablation endpoint of each individual lesion was elimination of the negative component of the unipolar atrial signal. The procedural endpoint was PVI with bidirectional block. RESULTS: All PVs were successfully isolated. After 30 min of waiting time, 35 patients (16%) had PV reconnection and in all of them, the PVs were re-isolated. Two years after a single ablation procedure, 187 patients (87%) remained arrhythmia free, without anti-arrhythmic drugs. Of the 28 patients presenting with AF recurrence, 25 had PV reconnection and underwent repeat PVI while in the remaining 3 patients, all four PVs were isolated and extra-PV triggers were identified. There were six groin hematomas and one transient ischemic attack. CONCLUSIONS: Unipolar atrial signal analysis combined with CF sensing ensures a robust 2-year SR maintenance rate in the treatment of PAF. Clinical trial registration-URL: http://www.clinicaltrials.gov . Unique identifier: NCT02520960.

Explosion of tuberculin-specific Th1-responses induces immune restoration syndrome in tuberculosis and HIV co-infected patients.

OBJECTIVES: To test the hypothesis that an acute exacerbation of mycobacteria-specific Th1 response after HIV infection control by HAART causes immune restoration syndrome (IRS) in HIV-tuberculosis (TB) coinfected patients. DESIGN: Prospective, multicenter study of 19 consecutive untreated HIV-TB coinfected patients included when initiating antimycobacterial therapy and sequentially evaluated during HAART and at time of IRS. IRS was defined according to classical clinical diagnostic criteria. Patients were declared IRS- if no IRS occurred within 3 months after HAART initiation. METHODS: Mycobacteria-specific [purified protein derivative (PPD), ESAT-6, 85B] Th1 cells producing interferon (IFN)-gamma quantified by ELISpot, in vitro production of 25 cytokines/chemokines in antigen-stimulated peripheral blood mononuclear cell (PBMC) supernatants quantified by chemiluminescence. RESULTS: Seven patients (37%) experienced IRS (IRS+). Mycobacteria-specific (PPD) Th1 IFN-gamma-producing cells increased sharply during IRS (median, 2970 spot forming cells/10 PBMC), but not the cytomegalovirus-specific responses tested as control. Only three IRS+ patients had low ESAT-6- but no 85B-specific responses. IRS- patients did not develop acute PPD-specific responses except in one case. In addition, at time of IRS a peak of PPD-specific Th1 cytokines/chemokines [interleukin (IL)-2, IL-12, IFN-gamma, IP10 and monokine-induced by IFN-gamma] without Th2 cytokines, and a peak of non-specific inflammatory cytokines/chemokines (TNF-alpha, IL-6, IL-1beta, IL-10, RANTES and MCP-1) occurred. These findings were independent from CD4 cell count, viral loads or time of HAART initiation. CONCLUSION: An acute exacerbation of Th1 responses against mycobacterial antigens appears to cause IRS in patients co-infected with HIV and TB. This key event provides new evidence valuable for the diagnosis and treatment of IRS.

Deciphering the molecular bases of Mycobacterium tuberculosis binding to the lectin DC-SIGN reveals an underestimated complexity.

Interactions between dendritic cells and Mycobacterium tuberculosis, the aetiological agent of tuberculosis in humans, are thought to be central to anti-mycobacterial immunity. We have previously shown that M. tuberculosis binds to human monocyte-derived dendritic cells mostly through the C-type lectin DC-SIGN (dendritic-cell-specific intercellular molecule-3-grabbing non-integrin)/CD209, and we have suggested that DC-SIGN may discriminate between mycobacterial species through recognition of the mannose-capping residues on the lipoglycan lipoarabinomannan of the bacterial envelope. Here, using a variety of fast- and slow-growing Mycobacterium species, we provide further evidence that mycobacteria recognition by DC-SIGN may be restricted to species of the M. tuberculosis complex. Fine analyses of the lipoarabinomannan molecules purified from these species show that the structure and amount of these molecules alone cannot account for such a preferential recognition. We propose that M. tuberculosis recognition by DC-SIGN relies on both a potential difference of accessibility of lipoarabinomannan in its envelope and, more probably, on the binding of additional ligands, possibly including lipomannan, mannose-capped arabinomannan, as well as the mannosylated 19 kDa and 45 kDa [Apa (alanine/proline-rich antigen)] glycoproteins. Altogether, our results reveal that the molecular basis of M. tuberculosis binding to DC-SIGN is more complicated than previously thought and provides further insight into the mechanisms of M. tuberculosis recognition by the immune system.