BACKGROUND: Deep analgosedation (DAS) or general anesthesia (GA) is mandatory for pulsed-field ablation (PFA) of atrial fibrillation (AF). In contrast to DAS, GA (conventional or total intravenous anesthesia [TIVA]) requires airway management. To find the optimal sedation regimen, this study compared ketamine-remimazolam DAS and propofol-opioid TIVA to propofol-opioid DAS, focusing on sedation-related adverse events. METHODS: Patients indicated for AF catheter ablation were randomly assigned in a 1:1:1 ratio to (1) DAS using intermittent propofol-opioid boluses (arm P), (2) continuous remimazolam-ketamine DAS (arm R), or (3) continuous propofol-opioid TIVA with secured airways (arm TIVA). Catheter ablation was performed using the FARAPULSE system (Boston Scientific, MA, USA). The major exclusion criterion was obstructive sleep apnea syndrome. The primary endpoint was defined as a composite of hypoxemia, hypotensive, or hypertensive events requiring intervention or leading to procedure discontinuation. Secondary endpoints included hemodynamic instability events, procedure time, serious adverse events, and patient satisfaction. RESULTS: One-hundred and twenty-seven patients (mean age 62.9 ± 10.3 years, 35.1% female, 47.2% with paroxysmal AF) were enrolled and randomized to the P (N = 42), R (N = 43) or TIVA (N = 42) arms. The primary endpoint occurred in 85.7% of P pts., 27.9% of R pts., and 66.7% of TIVA pts. (P < 0.001), driven by hypoxemia in the P arm (100% of pts. with the primary endpoint) and by hypotension in the TIVA arm (100%). The R arm showed a similar distribution of hypoxemia (50%) and hypotensive (66.7%) events. No differences were observed in mean procedural times, rates of serious adverse events, and assessment of patient satisfaction. CONCLUSIONS: In PFA procedures for AF, remimazolam-ketamine DAS was superior to propofol-opioid regimens (either boluses or continuous) and had the lowest risk of hypoxemia and hypotensive events. More than 80% of patients undergoing conventional propofol-opioid analgosedation experienced hypoxemia.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: The PRAETORIAN trial investigated the efficacy and safety of the subcutaneous implantable cardioverter-defibrillator (S-ICD) compared with transvenous ICD (TV-ICD) and showed non-inferiority of the S-ICD with regard to the composite endpoint of device-related complications and inappropriate shocks (IAS) after 49.1 months. Complications associated with transvenous leads are expected to occur after longer follow-up. The PRAETORIAN-XL trial aims to investigate whether the S-ICD is superior to the TV-ICD with respect to device-related complications at 8-year follow-up. METHODS: The PRAETORIAN trial randomized patients with a class I or IIa indication for ICD therapy without the need for pacing to either S-ICD or TV-ICD among 39 centers in the US and Europe between March 2011 and January 2017. The follow-up was extended after 49.1 months with an additional four years, for the PRAETORIAN-XL trial. The primary endpoint was the composite of all device-related complications. Complications could be related or unrelated to the lead, and minor or major, with major complications being those requiring an invasive intervention. Endpoints were analyzed according to the modified intention-to-treat principle using a Fine-Gray subdistribution hazards model to account for competing risks. An as-treated analysis was performed using a Cox proportional hazards model with device type as time-dependent variable. RESULTS: Patients were randomized to S-ICD (N=426) and TV-ICD (N=423). Twenty-one percent of the S-ICD group versus 18% of the TV-ICD group was female. The median age at implantation was 63 (IQR 54-69) years for the S-ICD and 64 (IQR 56-69) years for the TV-ICD. After a median follow-up of 87.5 months, all device-related complications (major and minor combined) were not significantly different in the modified intention-to-treat analysis (sHR 0.73 (95%CI 0.48-1.12); P=0.15). However, TV-ICD patients more often had a major complication or lead-related complication (P=0.03 and P<0.001 respectively). Moreover, the as-treated analysis showed significantly more complications in patients with a TV-ICD compared with an S-ICD (HR 0.64 (95%CI 0.41-0.99); P=0.047). CONCLUSIONS: The PRAETORIAN-XL trial demonstrated that there was no significant difference between the S-ICD and TV-ICD in all device-related complications during long-term follow-up. However, the TV-ICD carries a higher risk of major and lead-related complications compared with S-ICD therapy. The S-ICD should therefore be considered in all patients without a pacing indication who are evaluated for ICD therapy.

• Publikační typ
• časopisecké články MeSH

BACKGROUND: Complete revascularization is the standard treatment for patients with ST-segment-elevation myocardial infarction and multivessel disease. The FIRE trial (Functional Assessment in Elderly Myocardial Infarction Patients With Multivessel Disease) confirmed the benefit of complete revascularization in a population of older patients, but the follow-up is limited to 1 year. Therefore, the long-term benefit (>1 year) of this strategy in older patients is debated. To address this, an individual patient data meta-analysis was conducted in patients with ST-segment-elevation myocardial infarction ≥75 years of age enrolled in randomized clinical trials investigating complete versus culprit-only revascularization strategies. METHODS: PubMed, Embase, and the Cochrane database were systematically searched to identify randomized clinical trials comparing complete versus culprit-only revascularization. Individual patient-level data were collected from the relevant trials. The primary end point was death, myocardial infarction, or ischemia-driven revascularization. The secondary end point was cardiovascular death or myocardial infarction. RESULTS: Data from 7 randomized clinical trials encompassing 1733 patients (917 randomized to culprit-only and 816 to complete revascularization) were analyzed. The median age was 79 [interquartile range, 77-83] years. Of the patients, 595 (34%) were female. Follow-up ranged from a minimum of 6 months to a maximum of 6.2 years (median, 2.5 [interquartile range, 1-3.8] years). Complete revascularization reduced the primary end point up to 4 years (hazard ratio, 0.78 [95% CI, 0.63-0.96]) but not at the longest available follow-up (hazard ratio, 0.83 [95% CI, 0.69-1.01]). Complete revascularization significantly reduced the occurrence of cardiovascular death or myocardial infarction at the longest available follow-up (hazard ratio, 0.76 [95% CI, 0.58-0.99]). This was observed even when censoring the follow-up at each year. Long-term rate of death did not differ between complete and culprit-only revascularization arms. CONCLUSIONS: In this individual patient data meta-analysis of older patients with ST-segment-elevation myocardial infarction and multivessel disease, complete revascularization reduced the primary end point of death, myocardial infarction, or ischemia-driven revascularization up to 4 years. At the longest follow-up, complete revascularization reduced the composite of cardiovascular death or myocardial infarction but not the primary end point. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022367898.

• Klíčová slova
• complete revascularization, meta-analysis, multivessel disease, myocardial infarction, older patients,
• MeSH
• infarkt myokardu s elevacemi ST úseků * mortalita   chirurgie   terapie   MeSH
• koronární angioplastika mortalita   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma * MeSH
• revaskularizace myokardu * metody   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• věkové faktory MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

BACKGROUND: Although intravenous tranexamic acid is used in cardiac surgery to reduce bleeding and transfusion, topical tranexamic acid results in lower plasma concentrations compared with intravenous tranexamic acid, which may lower the risk of seizures. We aimed to determine whether topical tranexamic acid reduces the risk of in-hospital seizure without increasing the risk of transfusion among cardiac surgery patients. METHODS: We conducted a multicenter, double dummy, blinded, randomized controlled trial of patients recruited by convenience sampling in academic hospitals undergoing cardiac surgery with cardiopulmonary bypass. Between September 17, 2019, and November 28, 2023, a total of 3242 patients from 16 hospitals in 6 countries were randomly assigned (1:1 ratio) to receive either intravenous tranexamic acid (control) through surgery or topical tranexamic acid (treatment) at the end of surgery. The primary outcome was seizure, and the secondary outcome was red blood cell transfusion. After the last planned interim analysis, when 75% of anticipated participants had completed follow up, the data and safety monitoring board recommended to terminate the trial, and upon unblinding, the operations committee stopped the trial for safety. RESULTS: Among 3242 randomized patients (mean age, 66.0 years; 77.7% male), in-hospital seizure occurred in 4 of 1624 patients (0.2%) in the topical group, and 11 of 1628 patients (0.7%) in the intravenous group (absolute risk difference, -0.5% [95% CI, -0.9 to 0.03]; P=0.07). Red blood cell transfusion occurred in 570 patients (35.1%) in the topical group and in 433 (26.8%) in the intravenous group (absolute risk difference, 8.3% [95% CI, 5.2-11.5]; P=0.007). The absolute risk difference in transfusion of ≥4 units of red blood cells in the topical group compared with the intravenous group was 8.2% (95% CI, 3.4-12.9). CONCLUSIONS: Among patients undergoing cardiac surgery, topical administration of tranexamic acid resulted in an 8.3% absolute increase in transfusion without reducing the incidence of seizure, compared with intravenous tranexamic acid. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03954314.

• Klíčová slova
• administration, intravenous, administration, topical, blood transfusion, seizures, thoracic surgery, tranexamic acid,
• MeSH
• antifibrinolytika * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• aplikace lokální * MeSH
• dvojitá slepá metoda MeSH
• intravenózní podání * MeSH
• kardiochirurgické výkony * škodlivé účinky   MeSH
• krvácení při operaci prevence a kontrola   MeSH
• kyselina tranexamová * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• výsledek terapie MeSH
• záchvaty prevence a kontrola   etiologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH
• Názvy látek
• antifibrinolytika * MeSH
• kyselina tranexamová * MeSH

• Klíčová slova
• anticoagulants, heart failure, heart-assist devices, randomized controlled trial,
• MeSH
• antikoagulancia * aplikace a dávkování   terapeutické užití   MeSH
• aplikace orální MeSH
• lidé středního věku MeSH
• lidé MeSH
• podpůrné srdeční systémy * MeSH
• prospektivní studie MeSH
• srdeční selhání farmakoterapie   terapie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antikoagulancia * MeSH

BACKGROUND: Sildenafil, approved for pulmonary arterial hypertension (PAH), has a recommended adult dose of 20 mg TID, with a previously approved 5-mg TID dose by the US Food and Drug Administration. Safety concerns arose because of common off-label use of higher doses, particularly after pediatric data linked higher doses to increased mortality. To assess this, the Food and Drug Administration mandated a study evaluating the effects of various sildenafil doses on mortality in adults with PAH. METHODS: This randomized, double-blind study compared sildenafil at doses of 5, 20, or 80 mg TID in adults with PAH. The primary objective was noninferiority of 80 mg of sildenafil versus 5 mg for all-cause mortality. Secondary end points included time to clinical worsening and change in 6-minute walk distance at 6 months. Interim analyses were planned at 50% and 75% of the anticipated mortality events. Safety and tolerability were assessed in the intention-to-treat population. RESULTS: The study was halted after the first interim analysis, demonstrating noninferiority for 80 mg of sildenafil versus 5 mg. Of 385 patients enrolled across all dose groups, 78 died. The primary analysis showed a hazard ratio of 0.51 (99.7% CI, 0.22-1.21; P<0.001 for noninferiority) for overall survival comparing 80 mg of sildenafil with 5 mg. Time to clinical worsening favored 80 mg of sildenafil compared with 5 mg (hazard ratio, 0.44 [99.7% CI, 0.22-0.89]; P<0.001). Sildenafil at 80 mg improved 6-minute walk distance from baseline at 6 months compared with 5 mg (least square mean change, 18.9 m [95% CI, 2.99-34.86]; P=0.0201). No significant differences were found between 80 mg of sildenafil and 20 mg in mortality, clinical worsening, and 6-minute walk distance. Adverse event-related drug discontinuations were numerically higher with 80 mg of sildenafil. CONCLUSIONS: Sildenafil at 80 mg was noninferior to sildenafil at 5 mg when examining all-cause mortality in adults with PAH. Secondary efficacy end points favored 80 mg of sildenafil over 5 mg. On the basis of these findings, the Food and Drug Administration recently revoked the approval of 5 mg of sildenafil for adults with PAH, reinforced 20 mg TID as the recommended dose, and now allows dose titration up to 80 mg TID, if needed. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02060487.

• Klíčová slova
• mortality, pulmonary arterial hypertension, safety, sildenafil citrate, survival,
• MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• inhibitory fosfodiesterasy 5 aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• plicní arteriální hypertenze farmakoterapie   mortalita   MeSH
• plicní hypertenze farmakoterapie   mortalita   MeSH
• senioři MeSH
• sildenafil citrát * aplikace a dávkování   terapeutické užití   škodlivé účinky   MeSH
• test chůzí MeSH
• vazodilatancia aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva 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
• randomizované kontrolované studie MeSH
• Názvy látek
• inhibitory fosfodiesterasy 5 MeSH
• sildenafil citrát * MeSH
• vazodilatancia MeSH

BACKGROUND: Left bundle branch area pacing (LBBAP) may be associated with greater improvement in left ventricular ejection fraction and reduction in death or heart failure hospitalization compared with biventricular pacing (BVP) in patients requiring cardiac resynchronization therapy. We sought to compare the occurrence of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) and new-onset atrial fibrillation (AF) in patients undergoing BVP and LBBAP. METHODS: The I-CLAS study (International Collaborative LBBAP Study) included patients with left ventricular ejection fraction ≤35% who underwent BVP or LBBAP for cardiac resynchronization therapy between January 2018 and June 2022 at 15 centers. We performed propensity score-matched analysis of LBBAP and BVP in a 1:1 ratio. We assessed the incidence of VT/VF and new-onset AF among patients with no history of AF. Time to sustained VT/VF and time to new-onset AF was analyzed using the Cox proportional hazards survival model. RESULTS: Among 1778 patients undergoing cardiac resynchronization therapy (BVP, 981; LBBAP, 797), there were 1414 propensity score-matched patients (propensity score-matched BVP, 707; propensity score-matched LBBAP, 707). The occurrence of VT/VF was significantly lower with LBBAP compared with BVP (4.2% versus 9.3%; hazard ratio, 0.46 [95% CI, 0.29-0.74]; P<0.001). The incidence of VT storm (>3 episodes in 24 hours) was also significantly lower with LBBAP compared with BVP (0.8% versus 2.5%; P=0.013). Among 299 patients with cardiac resynchronization therapy pacemakers (BVP, 111; LBBAP, 188), VT/VF occurred in 8 patients in the BVP group versus none in the LBBAP group (7.2% versus 0%; P<0.001). In 1194 patients with no history of VT/VF or antiarrhythmic therapy (BVP, 591; LBBAP, 603), the occurrence of VT/VF was significantly lower with LBBAP than with BVP (3.2% versus 7.3%; hazard ratio, 0.46 [95% CI, 0.26-0.81]; P=0.007). Among patients with no history of AF (n=890), the occurrence of new-onset AF >30 s was significantly lower with LBBAP than with BVP (2.8% versus 6.6%; hazard ratio, 0.34 [95% CI, 0.16-0.73]; P=0.008). The incidence of AF lasting >24 hours was also significantly lower with LBBAP than with BVP (0.7% versus 2.9%; P=0.015). CONCLUSIONS: LBBAP was associated with a lower incidence of sustained VT/VF and new-onset AF compared with BVP. This difference remained significant after adjustment for differences in baseline characteristics between patients with BVP and LBBAP. Physiological resynchronization by LBBAP may be associated with lower risk of arrhythmias compared with BVP.

• Klíčová slova
• arrhythmias, cardiac, atrial fibrillation, cardiac pacing, artificial, cardiac resynchronization therapy, defibrillators, implantable, tachycardia, ventricular,
• MeSH
• elektrokardiografie MeSH
• fibrilace komor epidemiologie   etiologie   terapie   MeSH
• funkce levé komory srdeční MeSH
• komorová tachykardie * epidemiologie   etiologie   terapie   MeSH
• lidé MeSH
• srdeční resynchronizační terapie * škodlivé účinky   MeSH
• srdeční selhání * epidemiologie   terapie   MeSH
• tepový objem MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Physical activity is pivotal in managing heart failure with reduced ejection fraction, and walking integrated into daily life is an especially suitable form of physical activity. This study aimed to determine whether a 6-month lifestyle walking intervention combining self-monitoring and regular telephone counseling improves functional capacity assessed by the 6-minute walk test (6MWT) in patients with stable heart failure with reduced ejection fraction compared with usual care. METHODS: The WATCHFUL trial (Pedometer-Based Walking Intervention in Patients With Chronic Heart Failure With Reduced Ejection Fraction) was a 6-month multicenter, parallel-group randomized controlled trial recruiting patients with heart failure with reduced ejection fraction from 6 cardiovascular centers in the Czech Republic. Eligible participants were ≥18 years of age, had left ventricular ejection fraction <40%, and had New York Heart Association class II or III symptoms on guidelines-recommended medication. Individuals exceeding 450 meters on the baseline 6MWT were excluded. Patients in the intervention group were equipped with a Garmin vívofit activity tracker and received monthly telephone counseling from research nurses who encouraged them to use behavior change techniques such as self-monitoring, goal-setting, and action planning to increase their daily step count. The patients in the control group continued usual care. The primary outcome was the between-group difference in the distance walked during the 6MWT at 6 months. Secondary outcomes included daily step count and minutes of moderate to vigorous physical activity as measured by the hip-worn Actigraph wGT3X-BT accelerometer, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity C-reactive protein biomarkers, ejection fraction, anthropometric measures, depression score, self-efficacy, quality of life, and survival risk score. The primary analysis was conducted by intention to treat. RESULTS: Of 218 screened patients, 202 were randomized (mean age, 65 years; 22.8% female; 90.6% New York Heart Association class II; median left ventricular ejection fraction, 32.5%; median 6MWT, 385 meters; average 5071 steps/day; average 10.9 minutes of moderate to vigorous physical activity per day). At 6 months, no between-group differences were detected in the 6MWT (mean 7.4 meters [95% CI, -8.0 to 22.7]; P=0.345, n=186). The intervention group increased their average daily step count by 1420 (95% CI, 749 to 2091) and daily minutes of moderate to vigorous physical activity by 8.2 (95% CI, 3.0 to 13.3) over the control group. No between-group differences were detected for any other secondary outcomes. CONCLUSIONS: Whereas the lifestyle intervention in patients with heart failure with reduced ejection fraction improved daily steps by about 25%, it failed to demonstrate a corresponding improvement in functional capacity. Further research is needed to understand the lack of association between increased physical activity and functional outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03041610.

• Klíčová slova
• behavior, cardiac rehabilitation, counseling, exercise, fitness trackers, walk test, walking,
• MeSH
• chůze MeSH
• dysfunkce levé srdeční komory * MeSH
• funkce levé komory srdeční MeSH
• kvalita života MeSH
• lidé MeSH
• senioři MeSH
• srdeční selhání * terapie   farmakoterapie   MeSH
• tepový objem MeSH
• životní styl MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

BACKGROUND: Patients with heart failure (HF) with preserved ejection fraction (HFpEF) and obesity experience a high burden of symptoms and functional impairment, and a poor quality of life. In the STEP-HFpEF trial (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity), once-weekly semaglutide 2.4 mg improved symptoms, physical limitations, and exercise function, and reduced inflammation and body weight. This prespecified analysis investigated the effects of semaglutide on the primary and confirmatory secondary end points across the range of the Kansas City Cardiomyopathy Questionnaire (KCCQ) scores at baseline and on all key summary and individual KCCQ domains. METHODS: STEP-HFpEF randomly assigned 529 participants with symptomatic HF, an ejection fraction of ≥45%, and a body mass index of ≥30 kg/m2 to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. Dual primary end points change in KCCQ-Clinical Summary Score (CSS) and body weight. Confirmatory secondary end points included change in 6-minute walk distance, a hierarchical composite end point (death, HF events, and change in KCCQ-CSS and 6-minute walk distance) and change in C-reactive protein. Patients were stratified by KCCQ-CSS tertiles at baseline. Semaglutide effects on the primary, confirmatory secondary, and select exploratory end points (N-terminal pro-brain natriuretic peptide) were examined across these subgroups. Semaglutide effects on additional KCCQ domains (Total Symptom Score [including symptom burden and frequency], Physical Limitations Score, Social Limitations Score, Quality of Life Score, and Overall Summary Score) were also evaluated. RESULTS: Baseline median KCCQ-CSS across tertiles was 37, 59, and 77 points, respectively. Semaglutide consistently improved primary end points across KCCQ tertiles 1 to 3 (estimated treatment differences [95% CI]: for KCCQ-CSS, 10.7 [5.4 to 16.1], 8.1 [2.7 to 13.4], and 4.6 [-0.6 to 9.9] points; for body weight, -11 [-13.2 to -8.8], -9.4 [-11.5 to -7.2], and -11.8 [-14.0 to -9.6], respectively; Pinteraction=0.28 and 0.29, respectively); the same was observed for confirmatory secondary and exploratory end points (Pinteraction>0.1 for all). Semaglutide-treated patients experienced improvements in all key KCCQ domains (estimated treatment differences, 6.7-9.6 points across domains; P≤0.001 for all). Greater proportion of semaglutide-treated versus placebo-treated patients experienced at least 5-, 10-, 15-, and 20-point improvements in all KCCQ domains (odds ratios, 1.6-2.9 across domains; P<0.05 for all). CONCLUSIONS: In patients with HFpEF and obesity, semaglutide produced large improvements in HF-related symptoms, physical limitations, exercise function, inflammation, body weight, and N-terminal pro-brain natriuretic peptide, regardless of baseline health status. The benefits of semaglutide extended to all key KCCQ domains. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04788511.

• Klíčová slova
• health status, heart failure, diastolic, obesity, quality of life, semaglutide, weight loss,
• MeSH
• glukagonu podobné peptidy * MeSH
• kvalita života * MeSH
• lidé MeSH
• natriuretický peptid typu B MeSH
• obezita farmakoterapie   MeSH
• srdeční selhání * diagnóza   farmakoterapie   MeSH
• tepový objem MeSH
• zánět MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• glukagonu podobné peptidy * MeSH
• natriuretický peptid typu B MeSH
• semaglutide MeSH Prohlížeč

BACKGROUND: In severely affected patients with catecholaminergic polymorphic ventricular tachycardia, beta-blockers are often insufficiently protective. The purpose of this study was to evaluate whether flecainide is associated with a lower incidence of arrhythmic events (AEs) when added to beta-blockers in a large cohort of patients with catecholaminergic polymorphic ventricular tachycardia. METHODS: From 2 international registries, this multicenter case cross-over study included patients with a clinical or genetic diagnosis of catecholaminergic polymorphic ventricular tachycardia in whom flecainide was added to beta-blocker therapy. The study period was defined as the period in which background therapy (ie, beta-blocker type [beta1-selective or nonselective]), left cardiac sympathetic denervation, and implantable cardioverter defibrillator treatment status, remained unchanged within individual patients and was divided into pre-flecainide and on-flecainide periods. The primary end point was AEs, defined as sudden cardiac death, sudden cardiac arrest, appropriate implantable cardioverter defibrillator shock, and arrhythmic syncope. The association of flecainide with AE rates was assessed using a generalized linear mixed model assuming negative binomial distribution and random effects for patients. RESULTS: A total of 247 patients (123 [50%] females; median age at start of flecainide, 18 years [interquartile range, 14-29]; median flecainide dose, 2.2 mg/kg per day [interquartile range, 1.7-3.1]) were included. At baseline, all patients used a beta-blocker, 70 (28%) had an implantable cardioverter defibrillator, and 21 (9%) had a left cardiac sympathetic denervation. During a median pre-flecainide follow-up of 2.1 years (interquartile range, 0.4-7.2), 41 patients (17%) experienced 58 AEs (annual event rate, 5.6%). During a median on-flecainide follow-up of 2.9 years (interquartile range, 1.0-6.0), 23 patients (9%) experienced 38 AEs (annual event rate, 4.0%). There were significantly fewer AEs after initiation of flecainide (incidence rate ratio, 0.55 [95% CI, 0.38-0.83]; P=0.007). Among patients who were symptomatic before diagnosis or during the pre-flecainide period (n=167), flecainide was associated with significantly fewer AEs (incidence rate ratio, 0.49 [95% CI, 0.31-0.77]; P=0.002). Among patients with ≥1 AE on beta-blocker therapy (n=41), adding flecainide was also associated with significantly fewer AEs (incidence rate ratio, 0.25 [95% CI, 0.14-0.45]; P<0.001). CONCLUSIONS: For patients with catecholaminergic polymorphic ventricular tachycardia, adding flecainide to beta-blocker therapy was associated with a lower incidence of AEs in the overall cohort, in symptomatic patients, and particularly in patients with breakthrough AEs while on beta-blocker therapy.

• Klíčová slova
• catecholaminergic polymorphic ventricular tachycardia, sudden cardiac death, ventricular arrhythmias,
• MeSH
• beta blokátory škodlivé účinky   MeSH
• defibrilátory implantabilní * MeSH
• flekainid škodlivé účinky   MeSH
• incidence MeSH
• katecholaminergní polymorfní komorová tachykardie MeSH
• klinické křížové studie MeSH
• komorová tachykardie * diagnóza   farmakoterapie   epidemiologie   MeSH
• lidé MeSH
• mladiství MeSH
• náhlá srdeční smrt epidemiologie   etiologie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• beta blokátory MeSH
• flekainid MeSH