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Europace : European Pacing,... Jun 2024To describe the rationale, design, delivery and baseline characteristics of STEEER-AF (Stroke prevention and rhythm control Treatment: Evaluation of an Educational...
Design and deployment of the STEEER-AF trial to evaluate and improve guideline adherence: A cluster-randomised trial by the European Society of Cardiology and European Heart Rhythm Association.
AIMS
To describe the rationale, design, delivery and baseline characteristics of STEEER-AF (Stroke prevention and rhythm control Treatment: Evaluation of an Educational programme of the European Society of Cardiology [ESC] in a cluster-Randomised trial in patients with Atrial Fibrillation).
METHODS & RESULTS
STEEER-AF is a pragmatic trial designed to objectively and robustly determine whether guidelines are adhered to in routine practice, and evaluate a targeted educational programme for healthcare professionals. Seventy centres were randomised in 6 countries (France, Germany, Italy, Poland, Spain and United Kingdom; 2022-2023). STEEER-AF centres recruited 1732 patients with a diagnosis of atrial fibrillation (AF), with mean age 68.9 years (SD 11.7), CHA2DS2-VASc score 3.2 (SD 1.8) and 647 (37%) women. 843 patients (49%) were in AF and 760 (44%) in sinus rhythm at enrolment. Oral anticoagulant therapy was prescribed in 1,543 patients (89%), with the majority receiving direct oral anticoagulants (1,378; 89%). Previous cardioversion, antiarrhythmic drug therapy or ablation was recorded in 836 patients (48.3%). 551 patients (31.8%) were currently receiving an antiarrhythmic drug, and 446 (25.8%) were scheduled to receive a future cardioversion or ablation. The educational programme engaged 195 healthcare professionals across centres randomised to the intervention group, consisting of bespoke interactive online learning and reinforcement activities, supported by national expert trainers.
CONCLUSION
The STEEER-AF trial was successfully deployed across six European countries to investigate guideline adherence in real-world practice, and evaluate if a structured educational programme for healthcare professionals can improve patient-level care.
REGISTRATION
Clinicaltrials.gov NCT04396418.
PubMed: 38940494
DOI: 10.1093/europace/euae178 -
Journal of Extracellular Vesicles Jul 2024Cardiac fibrosis is a common pathological feature of cardiovascular diseases that arises from the hyperactivation of fibroblasts and excessive extracellular matrix (ECM)...
Cardiac fibrosis is a common pathological feature of cardiovascular diseases that arises from the hyperactivation of fibroblasts and excessive extracellular matrix (ECM) deposition, leading to impaired cardiac function and potentially heart failure or arrhythmia. Extracellular vesicles (EVs) released by cardiomyocytes (CMs) regulate various physiological functions essential for myocardial homeostasis, which are disrupted in cardiac disease. Therefore, healthy CM-derived EVs represent a promising cell-free therapy for the treatment of cardiac fibrosis. To this end, we optimized the culture conditions of human adult CMs to obtain a large yield of EVs without compromising cellular integrity by using a defined combination of small molecules. EVs were isolated by ultracentrifugation, and their characteristics were analysed. Finally, their effect on fibrosis was tested. Treatment of TGFβ-activated human cardiac fibroblasts with EVs derived from CMs using our culture system resulted in a decrease in fibroblast activation markers and ECM accumulation. The rescued phenotype was associated with specific EV cargo, including multiple myocyte-specific and antifibrotic microRNAs, although their effect individually was not as effective as the EV treatment. Notably, pathway analysis showed that EV treatment reverted the transcription of activated fibroblasts and decreased several signalling pathways, including MAPK, mTOR, JAK/STAT, TGFβ, and PI3K/Akt, all of which are involved in fibrosis development. Intracardiac injection of CM-derived EVs in an animal model of cardiac fibrosis reduced fibrotic area and increased angiogenesis, which correlated with improved cardiac function. These findings suggest that EVs derived from human adult CMs may offer a targeted and effective treatment for cardiac fibrosis, owing to their antifibrotic properties and the specificity of cargo.
Topics: Myocytes, Cardiac; Humans; Extracellular Vesicles; Fibrosis; Fibroblasts; Animals; MicroRNAs; Extracellular Matrix; Signal Transduction; Transforming Growth Factor beta; Cells, Cultured; Mice; Adult
PubMed: 38940266
DOI: 10.1002/jev2.12461 -
Journal of Cardiovascular... Jun 2024
PubMed: 38940237
DOI: 10.1111/jce.16351 -
Circulation Jun 2024Current estimates of atrial fibrillation (AF)-associated mortality rely on claims- or clinical-derived diagnoses of AF, limit AF to a binary entity, or are confounded by...
BACKGROUND
Current estimates of atrial fibrillation (AF)-associated mortality rely on claims- or clinical-derived diagnoses of AF, limit AF to a binary entity, or are confounded by comorbidities. The objective of the present study is to assess the association between device-recognized AF and mortality among patients with cardiac implantable electronic devices capable of sensitive and continuous atrial arrhythmia detection. Secondary outcomes include relative mortality among cohorts with no AF, paroxysmal AF, persistent AF, and permanent AF.
METHODS
Using the deidentified Optum Clinformatics US claims database (2015 to 2020) linked to the Medtronic CareLink database, we identified individuals with a cardiac implantable electronic device who transmitted data ≥6 months after implantation. AF burden was assessed during the first 6 months after implantation (baseline period). Subsequent mortality, assessed from claims data, was compared between patients with and those without AF, with adjustment for age, geographic region, insurance type, Charlson Comorbidity Index, and implantation year.
RESULTS
Of 21 391 patients (age, 72.9±10.9 years; 56.3% male) analyzed, 7798 (36.5%) had device-recognized AF. During a mean of 22.4±12.9 months (median, 20.1 [12.8-29.7] months) of follow-up, the overall incidence of mortality was 13.5%. Patients with AF had higher adjusted all-cause mortality than patients without AF (hazard ratio, 1.29 [95% CI, 1.20-1.39]; <0.001). Among those with AF, patients with nonparoxysmal AF had the greatest risk of mortality (persistent AF versus paroxysmal AF: hazard ratio, 1.36 [95% CI, 1.18-1.58]; <.001; permanent AF versus paroxysmal AF: hazard ratio, 1.23 [95% CI, 1.14-1.34]; <.001).
CONCLUSIONS
After adjustment for potential confounding factors, presence of AF was associated with higher mortality than no AF in our cohort of patients with cardiac implantable electronic devices. Among those with AF, nonparoxysmal AF was associated with the greatest risk of mortality.
PubMed: 38940005
DOI: 10.1161/CIRCULATIONAHA.124.069757 -
Circulation Jun 2024Despite major advances in the clinical management of long QT syndrome, some patients are not fully protected by beta-blocker therapy. Mexiletine is a well-known sodium...
Therapeutic Efficacy of Mexiletine for Long QT Syndrome Type 2: Evidence From Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes, Transgenic Rabbits, and Patients.
BACKGROUND
Despite major advances in the clinical management of long QT syndrome, some patients are not fully protected by beta-blocker therapy. Mexiletine is a well-known sodium channel blocker, with proven efficacy in patients with sodium channel-mediated long QT syndrome type 3. Our aim was to evaluate the efficacy of mexiletine in long QT syndrome type 2 (LQT2) using cardiomyocytes derived from patient-specific human induced pluripotent stem cells, a transgenic LQT2 rabbit model, and patients with LQT2.
METHODS
Heart rate-corrected field potential duration, a surrogate for QTc, was measured in human induced pluripotent stem cells from 2 patients with LQT2 (KCNH2-p.A561V, KCNH2-p.R366X) before and after mexiletine using a multiwell multi-electrode array system. Action potential duration at 90% repolarization (APD) was evaluated in cardiomyocytes isolated from transgenic LQT2 rabbits (KCNH2-p.G628S) at baseline and after mexiletine application. Mexiletine was given to 96 patients with LQT2. Patients were defined as responders in the presence of a QTc shortening ≥40 ms. Antiarrhythmic efficacy of mexiletine was evaluated by a Poisson regression model.
RESULTS
After acute treatment with mexiletine, human induced pluripotent stem cells from both patients with LQT2 showed a significant shortening of heart rate-corrected field potential duration compared with dimethyl sulfoxide control. In cardiomyocytes isolated from LQT2 rabbits, acute mexiletine significantly shortened APD (∆APD shortening 113 ms), indicating a strong mexiletine-mediated shortening across different LQT2 model systems. Mexiletine was given to 96 patients with LQT2 either chronically (n=60) or after the acute oral drug test (n=36): 65% of the patients taking mexiletine only chronically and 75% of the patients who performed the acute oral test were responders. There was a significant correlation between basal QTc and ∆QTc during the test (= -0.8; <0.001). The oral drug test correctly predicted long-term effect in 93% of the patients. Mexiletine reduced the mean yearly event rate from 0.10 (95% CI, 0.07-0.14) to 0.04 (95% CI, 0.02-0.08), with an incidence rate ratio of 0.40 (95% CI, 0.16-0.84), reflecting a 60% reduction in the event rate (=0.01).
CONCLUSIONS
Mexiletine significantly shortens cardiac repolarization in LQT2 human induced pluripotent stem cells, in the LQT2 rabbit model, and in the majority of patients with LQT2. Furthermore, mexiletine showed antiarrhythmic efficacy. Mexiletine should therefore be considered a valid therapeutic option to be added to conventional therapies in higher-risk patients with LQT2.
PubMed: 38939955
DOI: 10.1161/CIRCULATIONAHA.124.068959 -
Circulation Research Jun 2024Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachycardia in small case series of patients with refractory ventricular...
BACKGROUND
Thoracic epidural anesthesia (TEA) has been shown to reduce the burden of ventricular tachycardia in small case series of patients with refractory ventricular tachycardia and cardiomyopathy. However, its electrophysiological and autonomic effects in diseased hearts remain unclear, and its use after myocardial infarction is limited by concerns for potential right ventricular dysfunction.
METHODS
Myocardial infarction was created in Yorkshire pigs (N=22) by left anterior descending coronary artery occlusion. Six weeks after myocardial infarction, an epidural catheter was placed at the C7-T1 vertebral level for injection of 2% lidocaine. Right and left ventricular hemodynamics were recorded using Millar pressure-conductance catheters, and ventricular activation recovery intervals (ARIs), a surrogate of action potential durations, by a 56-electrode sock and 64-electrode basket catheter. Hemodynamics and ARIs, baroreflex sensitivity and intrinsic cardiac neural activity, and ventricular effective refractory periods and slope of restitution (S) were assessed before and after TEA. Ventricular tachyarrhythmia inducibility was assessed by programmed electrical stimulation.
RESULTS
TEA reduced inducibility of ventricular tachyarrhythmias by 70%. TEA did not affect right ventricular-systolic pressure or contractility although left ventricular-systolic pressure and contractility decreased modestly. Global and regional ventricular ARIs increased, including in scar and border zone regions post-TEA. TEA reduced ARI dispersion specifically in border zone regions. Ventricular effective refractory periods prolonged significantly at critical sites of arrhythmogenesis, and S was reduced. Interestingly, TEA significantly improved cardiac vagal function, as measured by both baroreflex sensitivity and intrinsic cardiac neural activity.
CONCLUSIONS
TEA does not compromise right ventricular function in infarcted hearts. Its antiarrhythmic mechanisms are mediated by increases in ventricular effective refractory period and ARIs, decreases in S, and reductions in border zone electrophysiological heterogeneities. TEA improves parasympathetic function, which may independently underlie some of its observed antiarrhythmic mechanisms. This study provides novel insights into the antiarrhythmic mechanisms of TEA while highlighting its applicability to the clinical setting.
PubMed: 38939925
DOI: 10.1161/CIRCRESAHA.123.324058 -
Frontiers in Pharmacology 2024Danhong injection (DHI) is widely used in the treatment of myocardial infarction (MI). We aimed to systematically review the efficacy and safety of DHI in a randomized...
OBJECTIVE
Danhong injection (DHI) is widely used in the treatment of myocardial infarction (MI). We aimed to systematically review the efficacy and safety of DHI in a randomized controlled experiment on MI.
METHODS
We searched the randomized controlled trials (RCTs) of DHI for MI published before 2 April 2023 in China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Wanfang database, China Science and Technology Journal Database (VIP), PubMed, Web of Science, Cochrance Library, and Embase databases. The methodological quality of the included studies was evaluated using the Cochrane Handbook 5.3 criteria using the RevMan software, and meta-analysis was performed and a forest map was drawn.
RESULTS
A total of 38 trials included 3877 patients, including 2022 cases in the DHI treatment group and 1855 cases in the control group. Meta-analysis showed that the total effective rate (RR = 1.18%, 95% CI [1.14-1.12]) during treatment with DHI was higher than that of the control group. The prevalence of cardiac arrhythmia (RR = 0.55%, 95% CI [0.46-0.65]) was lower than that of the control group. The incidence of heart rate failure (RR = 0.45%, 95% CI [0.30-0.70]) was lower than that of the control group. The prevalence of cardiogenic shock (RR = 0.33%, 95% CI [0.11-1.04]) was > 0.05, and the difference was not statistically significant. There was no statistically significant difference in LVEF between the two groups (MD = 0.00%, 95% CI [0.00-0.00]). CK-MB (MD = -0.81%, 95% CI [-0.92∼ -0.69]) was lower than the control group. hs-CRP (MD = -1.09, 95% CI [-1.22∼ -0.97]) was lower than the control group. The incidence of adverse reactions (RR = 0.37, The 95% CI [0.17-0.82]) was lower than that in the control group.
CONCLUSION
Basing on our study, the use of DHI in the treatment of myocardial infarction patients is effective, can improve cardiac function, reduce the incidence of adverse reactions, and improve the overall quality of life.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023390973.
PubMed: 38939841
DOI: 10.3389/fphar.2024.1371959 -
JACC. Advances Jan 2024
PubMed: 38939819
DOI: 10.1016/j.jacadv.2023.100718 -
JACC. Advances Jan 2024Multilevel obstruction in left ventricular inflow and outflow predisposes to arrhythmias in Shone's complex (SC).
BACKGROUND
Multilevel obstruction in left ventricular inflow and outflow predisposes to arrhythmias in Shone's complex (SC).
OBJECTIVES
The purpose of this study was to study the prevalence and outcomes (heart failure [HF] hospitalization, cardiac transplant, death) of cardiac arrhythmias in adults with SC.
METHODS
Adults with SC (defined as ≥2 lesions out of supramitral ring, parachute mitral valve, subvalvular/valvular aortic stenosis (AS), and aortic coarctation) seen at Mayo Clinic between January 1999 and March 2020 were identified and evaluated for the presence of sustained atrial fibrillation, atrial flutter, and ventricular arrhythmias (VA). Kaplan-Meier survival analysis was used to calculate the occurrence of these arrhythmias.
RESULTS
Seventy-three patients with SC (mean age at first visit 33 ± 13 years) were identified. Most common anomalies were valvular AS (88%), coarctation (85%), parachute mitral valve (44%), subvalvular AS (44%), and supramitral ring (25%). Atrial arrhythmias were diagnosed in 24 patients (33%) at a mean age of 34.6 ± 12.7 years. Patients with atrial fibrillation and atrial flutter had higher number of surgeries, left atrial size, right ventricular systolic pressure, and HF hospitalizations. A rhythm control approach was used in majority of patients (75% on antiarrhythmic drugs and 50% underwent catheter ablation). Sustained VA occurred in 6 of 73 patients of whom 4 had an ejection fraction <40%. Death and cardiac transplantation occurred in 11 and 3 patients, respectively, during a median follow-up of 7.3 ± 6.0 years.
CONCLUSIONS
In adults with SC, atrial arrhythmias occurred in one-third of patients, were associated with more HF hospitalizations, and frequently required rhythm control. Prevalence of sustained VA was 8% and implantable cardioverter-defibrillator implantation should be considered in those with reduced ejection fraction.
PubMed: 38939811
DOI: 10.1016/j.jacadv.2023.100715 -
Journal of Arrhythmia Jun 2024Implantable cardioverter-defibrillator (ICD) offers an opportunity to study inducibility of ventricular tachycardia (VT) or ventricular fibrillation (VF) by performing...
BACKGROUND
Implantable cardioverter-defibrillator (ICD) offers an opportunity to study inducibility of ventricular tachycardia (VT) or ventricular fibrillation (VF) by performing noninvasive programmed ventricular stimulation (NIPS). Whether NIPS can predict future arrhythmic events or mortality in patients with primary prevention ICD, has not yet been examined.
METHODS
From the NIPS-ICD study (ClinicalTrials ID: NCT02373306) 41 consecutive patients (34 males, age 64 ± 11 years, 76% ischemic cardiomyopathy [ICM]) had ICD for primary prevention indication. Patients underwent NIPS using a standardized protocol of up to three premature extrastimuli at 600, 500 and 400 ms drive cycle lengths. NIPS was classified as positive if sustained VT or VF was induced. The study endpoint was occurrence of sustained VT/VF during the follow-up.
RESULTS
At baseline NIPS, VT/VF was induced in 8 (20%) ICM patients. During the 5-year follow-up, the VT/VF occurred in 7 (17%) patients, all with ICM. The difference between NIPS-inducible versus NIPS-noninducible patients regarding VT/VF occurrence did not meet statistical significance (38% vs. 12%, log rank test = .11). After a 5-year follow-up, the mortality rate was significantly higher in patients who had VT/VF induced at NIPS versus no VT/VF at NIPS (38% vs. 12%, = .043). The occurrence of a composite endpoint consisting of VT/VF recurrence or death in patients with ICM was also most frequent in the NIPS-inducible group (75% vs. 35%, = .037).
CONCLUSIONS
Inducibility of VT/VF during NIPS in ICM patients with primary prevention ICD is associated with higher mortality and higher incidence of composite endpoint consisting of death or VT/VF during a long-term observation.
PubMed: 38939799
DOI: 10.1002/joa3.13017