BACKGROUND: Conduction system pacing (CSP), including both left bundle branch area pacing (LBBAP) and His-bundle pacing (HBP) has been proposed as an alternative therapy option for patients with indication for cardiac pacing to treat bradycardia or heart failure. OBJECTIVE: The purpose of this study was to evaluate implant success, safety, and electrical performances of HBP and LBBAP in the multinational Physiological Pacing Registry. METHODS: The international prospective observational registry included 44 sites from 16 countries globally between November 2018 and May 2021. RESULTS: Of 870 subjects enrolled, CSP lead implantation was attempted in 849 patients. Subjects with successful CSP lead implantation were followed for 6 months (5 ± 2 months). CSP lead implantation was successful in 768 patients (90.4%). Implant success was 95.2% (239/251) for LBBAP and 88.5% (529/598) for HBP (P = .002). Procedural duration and fluoroscopy duration were comparable between LBBAP and HBP (P = .537). Capture threshold at implant was 0.69 ± 0.39 V at 0.46 ± 0.15 ms in LBBAP and 1.44 ± 1.03 V at 0.71 ± 0.33 ms in HBP (P <.001). Capture threshold at 6 months was 0.79 ± 0.33 V at 0.44 ± 0.13 ms in LBBAP and 1.59 ± 0.97 V at 0.67 ± 0.31 ms in HBP (P <.001). Pacing threshold rise ≥1 V was observed at 6 months in 3 of 208 (1.4%) of LBBAP and 55 of 418 (13.2%) of HBP (P <.001). Serious adverse events related to implant procedure or CSP lead occurred in 5 of 251 (2.0%) with LBBAP and 25 of 598 (4.2%) with HBP (P = .115). CONCLUSION: This large prospective multicenter study demonstrates that CSP is technically feasible in most patients with relatively higher implant success and suggests that, with current technology, LBBAP may have better pacing parameters than HBP.

• MeSH
• elektrokardiografie metody   MeSH
• Hisův svazek * MeSH
• kardiostimulace umělá * metody   MeSH
• lidé MeSH
• nemoci převodního systému srdečního etiologie   MeSH
• prospektivní studie MeSH
• registrace MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

PURPOSE: Nucleophosmin 1 (NPM1) mutations are associated with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms-related tyrosine kinase 3 gene (FLT3) is absent (FLT3-ITDneg) or present with a low allelic ratio (FLT3-ITDlow). The 2017 European LeukemiaNet guidelines assume this is true regardless of accompanying cytogenetic abnormalities. We investigated the validity of this assumption. METHODS: We analyzed associations between karyotype and outcome in intensively treated patients with NPM1mut/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers. RESULTS: Among 2,426 patients with NPM1mut/FLT3-ITDneg/low AML, 2,000 (82.4%) had a normal and 426 (17.6%) had an abnormal karyotype, including 329 patients (13.6%) with intermediate and 83 patients (3.4%) with adverse-risk chromosomal abnormalities. In patients with NPM1mut/FLT3-ITDneg/low AML, adverse cytogenetics were associated with lower complete remission rates (87.7%, 86.0%, and 66.3% for normal, aberrant intermediate, and adverse karyotype, respectively; P < .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P < .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P < .001), and a higher 5-year cumulative incidence of relapse (43.6%, 44.2%, 51.9%, respectively; P = .0012). These associations remained in multivariable mixed-effects regression analyses adjusted for known clinicopathologic risk factors (P < .001 for all end points). In patients with adverse-risk chromosomal aberrations, we found no significant influence of the NPM1 mutational status on outcome. CONCLUSION: Karyotype abnormalities are significantly associated with outcome in NPM1mut/FLT3-ITDneg/low AML. When adverse-risk cytogenetics are present, patients with NPM1mut share the same unfavorable prognosis as patients with NPM1 wild type and should be classified and treated accordingly. Thus, cytogenetic risk predominates over molecular risk in NPM1mut/FLT3-ITDneg/low AML.

• MeSH
• akutní myeloidní leukemie genetika   MeSH
• chromozomální aberace MeSH
• dospělí MeSH
• jaderné proteiny genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• tyrosinkinasa 3 podobná fms genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: In the ICD Sports Safety Registry, death, arrhythmia- or shock-related physical injury did not occur in athletes who continue competitive sports after implantable cardioverter-defibrillator (ICD) implantation. However, data from non-competitive ICD recipients is lacking. This report describes arrhythmic events and lead performance in intensive recreational athletes with ICDs enrolled in the European recreational arm of the Registry, and compares their outcome with those of the competitive athletes in the Registry. METHODS: The Registry recruited 317 competitive athletes ≥ 18 years old, receiving an ICD for primary or secondary prevention (234 US; 83 non-US). In Europe, Israel and Australia only, an additional cohort of 80 'auto-competitive' recreational athletes was also included, engaged in intense physical activity on a regular basis (≥2×/week and/or ≥ 2 h/week) with the explicit aim to improve their physical performance limits. Athletes were followed for a median of 44 and 49 months, respectively. ICD shock data and clinical outcomes were adjudicated by three electrophysiologists. RESULTS: Compared with competitive athletes, recreational athletes were older (median 44 vs. 37 years; p = 0.0004), more frequently men (79% vs. 68%; p = 0.06), with less idiopathic ventricular fibrillation or catecholaminergic polymorphic ventricular tachycardia (1.3% vs. 15.4%), less congenital heart disease (1.3% vs. 6.9%) and more arrhythmogenic right ventricular cardiomyopathy (23.8% vs. 13.6%) ( p < 0.001). They more often had a prophylactic ICD implant (51.4% vs. 26.9%; p < 0.0001) or were given a beta-blocker (95% vs. 65%; p < 0.0001). Left ventricular ejection fraction, ICD rate cut-off and time from implant were similar. Recreational athletes performed fewer hours of sports per week (median 4.5 vs. 6 h; p = 0.0004) and fewer participated in sports with burst-performances ( vs. endurance) as their main sports: 4% vs. 65% ( p < 0.0001). None of the athletes in either group died, required external resuscitation or was injured due to arrhythmia or shock. Freedom from definite or probable lead malfunction was similar (5-year 97% vs. 96%; 10-year 93% vs. 91%). Recreational athletes received fewer total shocks (13.8% vs. 26.5%, p = 0.01) due to fewer inappropriate shocks (2.5% vs. 12%; p = 0.01). The proportion receiving appropriate shocks was similar (12.5% vs. 15.5%, p = 0.51). Recreational athletes received fewer total (6.3% vs. 20.2%; p = 0.003), appropriate (3.8% vs. 11.4%; p = 0.06) and inappropriate (2.5% vs. 9.5%; p = 0.04) shocks during physical activity. Ventricular tachycardia/fibrillation storms during physical activity occurred in 0/80 recreational vs. 7/317 competitive athletes. Appropriate shocks during physical activity were related to underlying disease ( p = 0.004) and competitive versus recreational sports ( p = 0.004), but there was no relation with age, gender, type of indication, beta-blocker use or burst/endurance sports. The proportion of athletes who stopped sports due to shocks was similar (3.8% vs. 7.5%, p = 0.32). CONCLUSIONS: Participants in recreational sports had less frequent appropriate and inappropriate shocks during physical activity than participants in competitive sports. Shocks did not cause death or injury. Recreational athletes with ICDs can engage in sports without severe adverse outcomes unless other reasons preclude continuation.

• MeSH
• defibrilátory implantabilní MeSH
• dospělí MeSH
• elektrická defibrilace * škodlivé účinky   přístrojové vybavení   mortalita   MeSH
• hodnocení rizik MeSH
• kompetitivní chování MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• náhlá srdeční smrt epidemiologie   prevence a kontrola   MeSH
• primární prevence MeSH
• prospektivní studie MeSH
• registrace MeSH
• rizikové faktory MeSH
• sekundární prevence MeSH
• sportovci * MeSH
• sporty * MeSH
• srdeční arytmie diagnóza   mortalita   patofyziologie   terapie   MeSH
• tělesná námaha * MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH

OBJECTIVE: We aimed to analyse the effect of the introduction of fingolimod, the first oral disease-modifying therapy, on treatment utilisation and persistence in an international cohort of patients with multiple sclerosis (MS). METHODS: MSBASIS, a prospective, observational sub-study of the MSBase registry, collects demographic, clinical and paraclinical data on patients followed from MS onset (n=4718). We conducted a multivariable conditional risk set survival analysis to identify predictors of treatment discontinuation, and to assess if the introduction of fingolimod has altered treatment persistence. RESULTS: A total of 2640 patients commenced immunomodulatory therapy. Following the introduction of fingolimod, patients were more likely to discontinue all other treatments (hazard ratio 1.64, p<0.001) while more patients switched to fingolimod than any other therapy (42.3% of switches). Patients switched to fingolimod due to convenience. Patients treated with fingolimod were less likely to discontinue treatment compared with other therapies (p<0.001). Female sex, country of residence, younger age, a high Expanded Disability Status Scale score and relapse activity were all independently associated with higher rates of treatment discontinuation. CONCLUSION: Following the availability of fingolimod, patients were more likely to discontinue injectable treatments. Those who switched to fingolimod were more likely to do so for convenience. Persistence was improved on fingolimod compared to other medications.

• MeSH
• adherence k farmakoterapii * MeSH
• aplikace orální MeSH
• časové faktory MeSH
• demyelinizační nemoci diagnóza   farmakoterapie   imunologie   MeSH
• dospělí MeSH
• fingolimod hydrochlorid aplikace a dávkování   škodlivé účinky   MeSH
• imunosupresiva aplikace a dávkování   škodlivé účinky   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• multivariační analýza MeSH
• náhrada léků * MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• registrace MeSH
• relabující-remitující roztroušená skleróza diagnóza   farmakoterapie   imunologie   MeSH
• rizikové faktory MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

BACKGROUND: The results of head-to-head comparisons of injectable immunomodulators (interferon β, glatiramer acetate) have been inconclusive and a comprehensive analysis of their effectiveness is needed. OBJECTIVE: We aimed to compare, in a real-world setting, relapse and disability outcomes among patients with multiple sclerosis (MS) treated with injectable immunomodulators. METHODS: Pairwise analysis of the international MSBase registry data was conducted using propensity-score matching. The four injectable immunomodulators were compared in six head-to-head analyses of relapse and disability outcomes using paired mixed models or frailty proportional hazards models adjusted for magnetic resonance imaging variables. Sensitivity and power analyses were conducted. RESULTS: Of the 3326 included patients, 345-1199 patients per therapy were matched (median pairwise-censored follow-up was 3.7 years). Propensity matching eliminated >95% of the identified indication bias. Slightly lower relapse incidence was found among patients treated with glatiramer acetate or subcutaneous interferon β-1a relative to intramuscular interferon β-1a and interferon β-1b (p≤0.001). No differences in 12-month confirmed progression of disability were observed. CONCLUSION: Small but statistically significant differences in relapse outcomes exist among the injectable immunomodulators. MSBase is sufficiently powered to identify these differences and reflects practice in tertiary MS centres. While the present study controlled indication, selection and attrition bias, centre-dependent variance in data quality was likely.

• MeSH
• glatiramer acetát terapeutické užití   MeSH
• imunologické faktory terapeutické užití   MeSH
• interferon beta terapeutické užití   MeSH
• lidé MeSH
• registrace MeSH
• relabující-remitující roztroušená skleróza farmakoterapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH