Beta-blocker Therapy Research Articles

Effects of beta-blockers on quality of life and well-being in patients with myocardial infarction and preserved left ventricular function-a prespecified substudy from REDUCE-AMI.

In the Randomized Evaluation of Decreased Usage of Beta-Blockers after Acute Myocardial Infarction (REDUCE-AMI) study, long-term beta-blocker use in patients after acute myocardial infarction (AMI) with preserved left ventricular ejection fraction demonstrated no effect on death or cardiovascular outcomes. The aim of this prespecified substudy was to investigate effects of beta-blockers on self-reported quality of life and well-being. From this parallel-group, open-label, registry-based randomized clinical trial, EQ-5D, and World Health Organization well-being index-5 (WHO-5) questionnaires were obtained at 6-10 weeks and 11-13 months after AMI in 4080 and 806 patients, respectively. We report results from intention-to-treat and on-treatment analyses for the overall population and relevant subgroups using Wilcoxon rank sum test and adjusted ordinal regression analyses. Of the 4080 individuals reporting EQ-5D (median age 64 years, 22% female), 2023 were randomized to beta-blockers. The main outcome, median EQ-5D index score, was 0.94 [interquartile range (IQR) 0.88, 0.97] in the beta-blocker group, and 0.94 (IQR 0.88, 0.97) in the no-beta-blocker group 6-10 weeks after AMI, OR 1.00 [95% CI 0.89-1.13; P>0.9]. After 11-13 months, results remained unchanged. Findings were robust in on-treatment analyses and across relevant subgroups. Secondary outcomes, EQ-VAS and WHO-5 index score, confirmed these results. Among patients after AMI with preserved left ventricular ejection fraction, self-reported quality of life and well-being was not significantly different in individuals randomized to routine long-term beta-blocker therapy as compared to individuals with no beta-blocker use. These results appear consistent regardless of adherence to randomized treatment and across subgroups which emphasizes the need for a careful individual risk-benefit evaluation prior to initiation of beta-blocker treatment.

Cholinesterase Inhibitor Initiation Does Not Increase the Risk of Fall-Related Injury in Older Adults Treated With Beta-Blockers: A Self-Controlled Case Series Design.

Prescribing cholinesterase inhibitors (ChEIs) concurrently with beta-blockers might cause syncope that increases the risk of fall-related injuries (FRIs). This self-controlled case series study assesses the risk of FRIs associated with initiating ChEIs while receiving beta-blockers among Medicare fee-for-service-insured nursing home (NH) residents in the United States. We identified individuals at their first dispensing of a beta-blocker between 2016 and 2019 after at least 45 days of long-stay NH residency. Individuals were followed from the first day of beta-blocker use until beta-blocker discontinuation, Medicare disenrollment, death, or study end. ChEI initiation was classified as the first 60 days of new ChEI dispensing after 45 days of no ChEI exposure. FRIs were assessed during beta-blocker use periods, and age-adjusted incidence rate ratios (IRR) for ChEI-initiation days versus other days were calculated using conditional Poisson regression models. Analyses were weighted for event-dependent observation periods due to the high risk of mortality after an FRI in this population. Subgroup analyses were conducted for several key time-fixed variables, including sex, age, ChEI type, ChEI dose, beta-blocker selectivity, and beta-blocker dose. The FRI risk after ChEI initiation was not elevated among 837 residents who experienced an FRI while using beta-blockers (IRR=0.90 [95%CLs 0.71, 1.15]). Analyses of ChEI initiation in several subgroups yielded similar results. There was no substantial difference in FRI risk when initiating ChEIs among older NH residents receiving beta-blocker therapy versus periods without ChEI initiation, suggesting that there is no clinically significant pharmacodynamic drug-drug interaction between beta-blockers and ChEIs.

Impact of adherence to beta-blockers in all-comers ST-segment elevation myocardial infarction (STEMI) patients and according to left ventricular ejection fraction (LVEF) at discharge: results from the real-world registry FAST-STEMI.

Beta-blockers are a crucial part of post-myocardial infarction (MI) pharmacological therapy. Recent studies have raised questions about their efficacy in patients without reduced left ventricular ejection fraction (LVEF). This study aims to assess adherence to beta-blockers after discharge for ST-segment elevation myocardial infarction (STEMI) and the impact of adherence on outcomes based on LVEF at discharge. The retrospective registry FAST-STEMI evaluated real-world adherence to main cardiovascular drugs in STEMI patients between 2012 and 2017 by comparing purchased tablets to expected ones at one year through pharmacy registries. Optimal adherence was defined ≥80%. Primary outcomes included all-cause and cardiovascular death, while secondary outcomes were myocardial infarction, major/minor bleeding events, and ischemic stroke The study included 4688 patients discharged on beta-blockers. Mean age was 64 ± 12.3 years, 76% were male, and mean LVEF was 49.2 ± 8.8%. Mean adherence at one year was 87.1%. Optimal adherence was associated with lower all-cause (adjHR 0.62, 95%CI 0.41-0.92, p 0.02) and cardiovascular mortality (adjHR 0.55, 95%CI 0.26-0.98, p 0.043). In LVEF ≤40% patients, optimal adherence was linked to reduced all-cause and cardiovascular mortality but this was not found either in patients with preserved or mildly reduced LVEF. Predictors of cardiovascular mortality included older age, chronic kidney disease, male gender, and atrial fibrillation. Optimal adherence to beta-blocker therapy in all-comers STEMI patients reduced all-cause and cardiovascular mortality at 1 year; once stratified by LVEF, this effect is confirmed only in patients with reduced LVEF (< 40%) at hospital discharge.

Mitral regurgitation evolution after transcatheter tricuspid valve interventions - a sub-analysis of the TriValve Registry.

Transcatheter tricuspid valve interventions (TTVI) are increasingly used to treat patients with significant tricuspid regurgitation (TR). The evolution of concurrent mitral regurgitation (MR) severity after TTVI is currently unknown and may be pivotal for clinical decision-making. The aim of this study was to assess the evolution of MR after TTVI and to identify predictors of MR worsening and improvement. This analysis is a substudy of the Trivalve Registry, an international registry designed to collect data on TTVI. This substudy included all patients with echocardiographic data on MR evolution and excluded those with a concomitant tricuspid and mitral transcatheter valve intervention or with a history of mitral valve intervention. The co-primary outcomes were MR improvement and worsening at two timepoints: pre-discharge and 2-month follow-up. This analysis included 359 patients with severe TR, mostly(80%) treated with tricuspid transcatheter edge-to-edge repair(T-TEER). MR improvement was found in 106(29.5%) and 99(34%) patients, while MR worsening in 34(9.5%) and 33(11%) patients at pre-discharge and 2-month follow-up, respectively. Annuloplasty and heterotopic replacement were associated with MR worsening. Independent predictors of MR improvement were: atrial fibrillation, T-TEER, acute procedural success, TR reduction, LVEDD>60 mm and beta-blocker therapy. Patients with moderate-to-severe/severe MR following TTVI showed significantly higher death rates. MR degree variation is common after TTVI, with most cases showing improvement. Clinical and procedural characteristics may predict the MR evolution, in particular procedural success and T-TEER play key roles in MR outcomes. TTVI may be beneficial even in the presence of functional MR.

Therapeutic Efficacy of Mexiletine for Long QT Syndrome Type 2: Evidence From Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes, Transgenic Rabbits, and Patients.

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. 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 (APD90) 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. 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 APD90 by 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 (r= -0.8; P<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 (P=0.01). 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.

Abstract We107: Reduction of Six-Month Heart Failure Readmission Rates in Patients Undergoing MitraClip with Beta Receptor Blockade

Introduction: MitraClip has been shown to reduce heart failure readmissions in patients with moderate to severe mitral valve regurgitation. Likewise, beta-blocker (BB) therapy has been shown to reduce morbidity and mortality in select heart failure patients. At the cellular level, chronic myocardial insult from ongoing heart failure and mitral regurgitation leads to persistent overstimulation of myocardial beta-receptors, ultimately reducing cardiac inotropic reserve and contributing to myocardial injury. Thus, we hypothesized that patients on beta-blocker therapy before the MitraClip procedure would have fewer heart failure-related readmissions. Hypothesis: We assessed the hypothesis that beta-blocker therapy before the MitraClip procedure would lead to fewer heart failure-related readmissions by conducting a retrospective cohort study. This would help us better understand the pathogenesis of re-admissions in this patient population as well as help us decide whether prophylactic initiation of BB therapy before the procedure would reduce the risk of heart failure readmissions. Methods: We reviewed the records of patients who underwent the MitraClip procedure at our institution from January 2017 to July 2022. Patients without listed home medications, as well as non-heart failure-related readmissions and deaths, were excluded. Patients were split into those on BB therapy and those with no BB therapy. Of the 401 charts screened, 324 met the inclusion criteria. Results: From those who met the inclusion criteria, 226 patients were on beta-blocker therapy, while 98 patients were not. Of those who had at least one heart failure-related readmission within 6 months of the MitraClip procedure, 18 patients were on beta-blocker therapy and 16 patients were not. Meaning a 7.96% readmission rate for patients on beta-blocker therapy, and a 16.32% readmission rate for those who were not (OR 2.05, 95% CI: 1.004 to 4.186, p&lt;0.05), with the number needed to treat being 11.9. Conclusions: Our data shows that the use of beta-blocker therapy was associated with a statistically significant decrease in 6-month heart failure readmissions in those undergoing the MitraClip procedure. This suggests that at the cellular level, cardiac beta receptor dysfunction plays an integral part in future hospitalizations in this population. In conclusion, beta-blocker therapy should be considered in heart failure patients planning to undergo the MitraClip procedure to reduce heart failure-related readmissions.

Assessing the Frequency of Continuation of Beta Blocker Therapy Among Patients Admitted With Acute Decompensated Heart Failure—A Pilot Audit in a Multi-Centre Australian Hospital

Assessing the Frequency of Continuation of Beta Blocker Therapy Among Patients Admitted With Acute Decompensated Heart Failure—A Pilot Audit in a Multi-Centre Australian Hospital

Effect of beta-blockade on mortality in patients with cardiac amyloidosis: A systematic review and meta-analysis.

The efficacy of beta-blockers in cardiac amyloidosis (CA) is unclear, and concerns persist that neurohormonal blockade could worsen symptoms of heart failure. We aimed to assess whether beta-blocker therapy is associated with improved survival in patients with CA. We conducted a systematic review and meta-analysis to examine the impact of beta-blocker therapy on mortality in patients with CA. A search of MEDLINE and EMBASE was performed in August 2023. Data were extracted from observational studies and synthesized with pooling and random effects meta-analysis. Thirteen studies including 4215 patients with CA were incorporated in this review (3688 transthyretin amyloid cardiomyopathy (ATTR-CM), 502 light chain amyloid cardiomyopathy (AL-CM), 25 not specified; age 74.8±5.5years, 76% male). Over half of the cohort (52%) received beta-blockers and the rate of beta-blocker withdrawal was 28%. All-cause mortality was 33% (range: 13-51%) after a median follow-up ranging from 13 to 36months. There was an inverse association between the pooled risk of mortality and the use of beta-blocker therapy at any time point (RR 0.48, 95% CI 0.29-0.80, I2=83%, P=0.005, seven studies). There was no association between mortality and beta-blocker use (RR 0.65, 95% CI 0.29-1.47, I2=88%, P=0.30) in the three studies that only included patients with ATTR-CM. The three studies that included patients with both ATTR-CM and AL demonstrated an association of beta-blocker use with reduced mortality (OR 0.43, 95% CI 0.29-0.63, I2=4%, P<0.001). The only study that solely included 53 patients with AL-CM, demonstrated improved survival among the 53% who were able to tolerate beta-blocker therapy (RR 0.26, 95% CI 0.08-0.79, P=0.02). The absence of information on staging of CA is an important limitation of this study. Treatment with beta-blockers may be associated with a survival benefit in patients with CA, but these findings are subject to selection and survivor biases. Definitive prospective randomized trials of conventional heart failure therapies are needed in CA.

Discontinuation of afterload-reducing drugs decreases left ventricular outflow tract obstruction in hypertrophic obstructive cardiomyopathy.

Hypertrophic cardiomyopathy (HCM), the most common genetic heart disease, is classified into hypertrophic non-obstructive and hypertrophic obstructive cardiomyopathy (HOCM). Patients with HOCM and coexisting heart failure or arterial hypertension are often prescribed afterload-reducing drugs. Although recommended in current guidelines, data on the direct effect of discontinuing afterload-reducing medication are scarce. This study aims to demonstrate the benefit of discontinuing afterload-reducing medication in HOCM patients. This monocentric retrospective analysis included 24 patients with HOCM with afterload-reducing medication, including angiotensin-converting enzyme inhibitors, angiotensin-1 receptor blocker and dihydropyridine-calcium channel blocker, at their first outpatient visit. Effects of discontinuing this medication on LVOTO were examined compared to patients with persistent use despite medical advice. 16 patients discontinued their afterload-reducing drugs, resulting in a significant decrease in median LVOT gradient from 86.5 [60.5-109.3] mmHg to 61.5 [28.3-97.50] mmHg (p = 0.0004). In 6 patients, beta-blocker therapy was initiated simultaneously, or the dose was increased. Regardless, LVOT gradient reduction was also significant in the remaining 10 patients (p = 0.001). The gradient was not changed significantly in the 8 patients continuing their afterload-reducing medication. Discontinuation of afterload-reducing drugs significantly decreases LVOTO. Our study underscores the significance of abstaining from afterload-reducing drugs in HOCM patients, particularly in patients with concomitant hypertension or heart failure. According to recently published European guidelines, HOCM patients should preferably be treated with beta-blockers or non-dihydropyridine-calcium channel blockers.

Beta-1 Receptor (β1) in the Heart Specific Indicate to Stereoselectivity

The β1 receptor is one of the three beta receptors present in the human body, namely β1, β2, and β3. The β1 receptor is predominantly located in the heart, where it plays a crucial role in regulating the heart rate and the force of contraction, thereby increasing the cardiac output and the efficiency of blood pumping throughout the body. This receptor is targeted by a variety of pharmaceutical agents known as beta-blockers, which are commonly used in the treatment of cardiovascular conditions such as hypertension, angina, and arrhythmias.The β1 receptor exhibits stereoselectivity, meaning that different enantiomers (chiral molecules) of beta blockers can have varying levels of effectiveness and side effects. This study focuses on the stereoselectivity of the β1 receptor and the clinical implications of this property. It includes an examination of various β1 blockers, such as propranolol (a non-selective beta blocker), and selective β1 blockers like atenolol, bisoprolol, nebivolol, metoprolol, esmolol, acebutolol, and betaxolol. Each of these drugs has a unique chemical structure, with specific functional groups that contribute to their selective action on the β1 receptor. Furthermore, the β2 receptor, which is mainly present in the bronchi and bronchioles, is responsible for bronchodilation, and the β3 receptor, found in the bladder, helps reduce urinary urgency. Understanding the distinct locations and functions of these receptors allows for the development of targeted therapies with minimal off-target effects. This review highlights the importance of stereoselectivity in the development and use of β1 blockers, discussing their chemical structures, pharmacological activities, and therapeutic uses. It also explores the potential for future research and development of more selective and effective β1 receptor agonists and antagonists, which could offer improved therapeutic outcomes for patients with cardiovascular diseases. This study underscores the significant role of the β1 receptor in cardiovascular health and provides insights into the ongoing advancements in beta-blocker therapy. By delving into the stereoselectivity and specific actions of these drugs, the research aims to enhance the understanding and optimization of β1 receptor-targeted treatments in clinical practice.

Plasma soluble fms-like tyrosine kinase-1, placental growth factor, and vascular endothelial growth factor system gene variants as predictors of survival in heart failure.

Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), components of the vascular endothelial growth factor (VEGF) system, play key roles in angiogenesis. Reports of elevated plasma levels of sFlt-1 and PlGF in coronary heart disease and heart failure (HF) led us to investigate their utility, and VEGF system gene single nucleotide polymorphisms (SNPs), as prognostic biomarkers in HF. ELISA assays for sFlt-1, PlGF and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed on baseline plasma samples from the PEOPLE cohort (n = 890), a study of outcomes among patients after an episode of acute decompensated HF. Eight SNPs potentially associated with sFlt-1 or PlGF levels were genotyped. sFlt-1 and PlGF were assayed in 201 subjects from the Canterbury Healthy Volunteers Study (CHVS) matched to PEOPLE participants. All-cause death was the major endpoint for clinical outcome considered. In PEOPLE participants, mean plasma levels for both sFlt-1 (125 ± 2.01 pg/ml) and PlGF (17.5 ± 0.21 pg/ml) were higher (both p < 0.044) than in the CHVS cohort (81.2 ± 1.31 pg/ml and 15.5 ± 0.32 pg/ml, respectively). sFlt-1 was higher in HF with reduced ejection fraction compared to HF with preserved ejection fraction (p = 0.005). The PGF gene SNP rs2268616 was univariately associated with death (p = 0.016), and was also associated with PlGF levels, as was rs2268614 genotype. Cox proportional hazards modelling (n = 695, 246 deaths) showed plasma sFlt-1, but not PlGF, predicted survival (hazard ratio 6.44, 95% confidence interval 2.57-16.1; p < 0.001) in PEOPLE, independent of age, NT-proBNP, ischaemic aetiology, diabetic status and beta-blocker therapy. Plasma sFlt-1 concentrations have potential as an independent predictor of survival and may be complementary to established prognostic biomarkers in HF.

Holter study of heart rate variability in children and adolescents with long QT syndrome.

This study aimed to retrospectively assess cardiac autonomic activity in children with LQTS, considering genotype, symptoms, sex, age, and beta-blocker therapy (BB) and compare it to healthy controls. Heart rate variability (HRV), using power spectrum analysis, was analyzed in 575 Holter recordings from 116 children with LQTS and in 69 healthy children. The data were categorized into four age-groups and four heart rate (HR) ranges. In LQT1 and LQT2, increasing HR corresponded to significantly lower low (LF) and high frequency (HF) compared to controls. Total power (PTOT) was lower in all LQT1 age-groups compared to controls at HR 120-140 bpm (1-15 years: p < .01; 15-18 years: p = .03). At HR 80-100, LQT1 patients aged 1-10 years had lower HF than LQT2 patients (1-5 years: p = .05; 5-10 years: p = .02), and LQT2 patients aged 15-18 years had lower HF than LQT1 patients (p < .01). Symptomatic patients aged 10-15 years had lower PTOT at HR 100-120 bpm than asymptomatic patients (p = .04). LQT1 girls aged 10-15 and 15-18 years had a lower PTOT (10-15 years: p = .04; 15-18 years: p = .02) than boys. This study shows a correlation between HR and changes in HRV parameters. At higher HRs, LQTS patients generally had lower HRV values than controls, suggesting an abnormal autonomic response. These results may strengthen the link between physical activity and arrhythmias in LQTS.

Comparison of Heart Rates in Patients Initiated on Ticagrelor Versus Other P2Y12 Inhibitors After an Inferior ST Elevation Myocardial Infarction (STEMI).

P2Y12 inhibitors have differing associations of bradyarrhythmias. Ticagrelor has been shown to increase adenosine plasma concentrations leading to increases in bradyarrhythmias. While clopidogrel and prasugrel have not been shown to have any association with bradyarrhythmias. The objective of this study was to determine heart rates after ticagrelor initiation compared to clopidogrel/prasugrel in inferior ST Elevation Myocardial Infarction (STEMI) patients. This was a retrospective, multicenter study conducted at 3 primary percutaneous coronary intervention (PCI) centers between January 1, 2017 and September 30, 2022. Adult patients were included if they were diagnosed with an inferior STEMI to the right coronary artery (RCA) and treated with PCI followed by an oral P2Y12 inhibitor. The primary outcome was heart rate at 48 hours or discharge, whichever first, after administration of ticagrelor compared to clopidogrel/prasugrel. This study reviewed 331 patients, 172 in the ticagrelor group and 159 in the clopidogrel/prasugrel group. There were no statistical differences between groups regarding the primary outcome, with a median heart rate of 76 beats per minute (bpm) [67-85] in the ticagrelor group versus 73 bpm [66-84] in the clopidogrel/prasugrel group (P = 0.238). No differences were observed between groups regarding any secondary outcomes. There were similar heart rates between ticagrelor and clopidogrel/prasugrel. There were also similarities in the ability to tolerate beta-blocker therapy after initiation of a P2Y12 inhibitor. The results of this study suggest that in inferior STEMIs when using ticagrelor as the P2Y12 inhibitor, there are not increased clinical manifestations of bradycardia.

Photoplethysmography recordings preceding onset atrial fibrillation show a higher heart rate variability - a TeleCheck-AF subanalysis

Abstract Background An increased heart rate variability (HRV), mostly assessed by 12-lead electrocardiogram (ECG) or long-term Holter monitoring, can be associated with the onset of atrial fibrillation (AF). Data evaluating HRV measurements using digital devices, especially those using photoplethysmography (PPG), in patients at risk for AF are sparse. In this analysis, we aimed to assess if hand-held-based non-continuous PPG measurements can provide short-term HRV to predict AF. Methods Patients from the TeleCheck-AF project with at least one PPG measurement in AF and one measurement in sinus rhythm (SR) were analyzed. Briefly, patients were provided with a PPG-based heart rate/rhythm monitoring smartphone app. They were instructed to record a PPG measurements three times daily and in case of symptoms for seven consecutive days. Short-term HRV using root mean square of successive normal-to-normal interval differences (RMSSD) was calculated in recordings in SR and compared between those not preceding and preceding an episode of AF (figure 1). Results Overall, 136 patients [56.3% men, median age 66 (59; 72) years] were included in the analysis. Median total number of recordings per patient was 24 (19; 30) including 4 (2;7) AF episodes per 1 week recording period. RMSSD was significantly higher in PPG measurements preceding an AF episode than in PPG measurements not preceding an AF episode [42.5 (33.2;70.7)ms vs. 41.1 (32.4;54.7)ms; p&amp;lt;0.001]. Between-group comparison revealed no significant difference for gender, age, previous ablation or betablocker therapy (p=0.824; p=0.484; p=0.519 and p=0.624, respectively). Conclusion Short-term HRV based on RMSSD, assessed by digital hand-held devices is significantly higher in PPG recordings preceding an AF episode than in measurements not preceding a consecutive AF episode. Whether PPG-recording derived short-term HRV can help to predict onset-AF warrants further study in larger populations. Figure 1: Patient example and exemplary analysis scheme, depicting the total number of recordings (n=14). HRV of recordings in sinus rhythm (SR) not preceding an episode of atrial fibrillation (AF) (A; grey circles) were compared to recordings preceding a consecutive AF episode (B; blue circles).Figure 1

Comparative analysis of antiarrhythmic drugs following atrial fibrillation ablation

Abstract Background Atrial fibrillation (AF) ablation has become an established therapeutic modality for rhythm control. However, the optimal post-ablation pharmacological strategy remains uncertain. The present study addresses this gap by conducting a comparative analysis of four commonly used antiarrhythmic drugs (amiodarone, propafenone, sotalol, and flecainide), both as standalone treatments and in combination with beta blockers, to determine their impact on mortality, hospitalization rates, and AF recurrence. Methods A multi-center, retrospective cohort study was conducted, including patients who underwent successful AF ablation between 20010 to 2020. The study population was divided into groups based on the prescribed antiarrhythmic drug regimen: amiodarone, propafenone, sotalol, flecainide, and respective combinations with beta blockers. Patient demographics, comorbidities, and procedural details were collected. Endpoints included all-cause mortality, hospitalization due to cardiovascular events, MACE and AF recurrence. Results A total of 908 patients were included in this study. The mean age was 66 years old, and 33% (n=297) were female patients. Of 908 patients, 35% (n=316) were prescribed amiodarone, 34% (n=305) propafenone, 8% (n=76) sotalol, and 6%% (n=51) flecainide post AF ablation. Association with beta blockers were observed in 55% (n=496) of cases. Amiodarone group had a 0,3% (n=1) mortality, 9% (n=27) of hospitalizations, 2% (n=5) of major cardiovascular events (MACE) and 32% (n=101) of AF recurrence. Propafenone group had a 1,3% (n=4) mortality, 4% (n=12) hospitalizations, 2% (n=5) of MACE and 27% (n=81) of AF recurrence. Sotalol group had a 4% (n=3) mortality, 6% (n=4) of hospitalizations, 3% (n=2) of MACE and 44% (n=32) of AF recurrence. Flecainide group had 0 cases of death, 2% (n=1) of hospitalization, 0 cases of MACE and 35% of recurrence. Amiodarone is associated with a lower risk of death (p=0,018 OR 0,13). The presence of betablockers did not affect the endpoints, namely, death, hospitalization, MACE or AF recurrence. There were no other statistically significant associations between variables. Conclusion This study evaluated the effectiveness of common antiarrhythmics, such as amiodarone, propafenone, sotalol, and flecainide, with and without beta blockers, in the post-AF ablation setting. In this study, amiodarone showed a lower risk of death. There were no other statistically significant associations between either antiarrhythmic drug and each endpoint. The presence of betablocker therapy did not interfere with the endpoints. The findings contribute to the ongoing discourse on the optimal pharmacological strategy for AF management post-ablation. Further prospective studies with larger sample sizes are warranted to validate and refine these observations, paving the way for evidence-based guidelines in tailoring antiarrhythmic drug regimens for improved patient outcomes

Atrioventricular Nodal Reentrant Tachycardia in Kartagener’s Syndrome

Single case report of a middle-aged patient with Kartagener’s syndrome who experienced recurrent paroxysmal supraventricular tachycardia. Despite optimized beta-blocker therapy, only cardioversion in emergency departments provided symptomatic relief. The unique electrocardiographic features of this condition and their significance in transaortic electrophysiological studies for diagnosis and treatment are highlighted.

Combination therapy of beta-blockers and digoxin is associated with increased risk of major adverse cardiovascular events and all-cause mortality in patients with atrial fibrillation: a report from the GLORIA–AF registry

The effect of digoxin and beta-blockers on cardiovascular outcomes and mortality remains unclear. The study aimed to determine differences in cardiovascular (CV) outcomes and death rates among patients with atrial fibrillation (AF) who were prescribed with beta-blockers, digoxin or combination therapy. Data from phase II/III of the prospective Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA–AF) were analysed. The risk of major cardiovascular events (MACE) and death among patients with different prescriptions using COX proportional hazard regression was considered. Propensity score (PS) matching and weighting were further used to adjust for potential confounders of prescription use. A total of 14,201 patients [median age: 71.0 (IQR 64.0–77.0) years; 46.2% female] were recruited. After a median follow-up of 3.0 (IQR 2.4–3.1) years, 864 MACE, and 988 all-cause deaths were recorded. The incidence rate (IR) of MACE was 22.4 (95%CI 21.0–24.0) per 1000 person-years, while the IR of all-cause death was 25.4 (95%CI 23.8–27.0) per 1000 person-years. After multivariate adjustment with Cox regression, the risk of MACE (HR 1.35, 95% CI 1.09–1.68) and the risk of all-cause death (HR 1.28, 95%CI 1.04–1.57) were significantly higher in the combination therapy group, compared to the beta-blockers alone group. The risks of MACE and all-cause death remained significant in both PS matched and PS weighted cohort Among AF patients, combination therapy of beta-blockers and digoxin was associated with higher risks of MACE and all-cause death compared to beta-blockers alone.

Prescribing beta-blockers to patients after acute myocardial infarction

In the treatment of patients with acute coronary syndrome in the pre-reperfusion era, one of the first-line drugs was beta-blockers. Now the management strategy of such patients has changed significantly. The results of these studies confirm the important role of beta-blockers in the therapy of patients who have undergone ACS in the era of reperfusion therapy. Beta-blocker therapy may be beneficial because of a potential reduction in the risk of all-cause death. The choice of vasodilatory drugs can provide benefits and additionally prevent the occurrence of complications.

REAL WORLD USAGE OF RANOLAZINE FOR ANTIARRHYTHMIC PURPOSES: SINGLE CENTER EXPERIENCE

Abstract Introduction Ranolazine is a late sodium current blocking drug developed as an antianginal agent, with good preliminary efficacy data even for antiarrhythmic purposes (both at atrial and at ventricular level). Objectives To evaluate patients’ clinical characteristics and antiarrhythmic efficacy of ranolazine in subjects with a history of atrial and/or ventricular arrhythmias, isolated or repetitive. Patients and methods we included patients who received a first prescription of ranolazine for antiarrhythmic purposes in our center from 1/2022 to 11/2023 and evaluated the survival free from major arrhythmic relapses/ablation. Results 93 patients were enrolled (66±13 years, 15% women): 59% with arterial hypertension, 26% diabetics, 46% with post–ischemic dilated heart disease, 32% with primary cardiomyopathy (including 11% with hypertrophic cardiomyopathy, 10% with LMNA, 14% with TTN), 46% with implantable cardioverter defibrillator, 9% with pacemaker. The mean LV ejection fraction was 42 ± 15%, the mean serum creatinine 1 ± 0.3 mg/dL. Half (50%) had a history of atrial arrhythmias in the 6 months before starting the drug, mainly paroxysmal atrial fibrillation (AF), 67% of ventricular arrhythmias (VAs), mainly isolated and repetitive premature ventricular beats (PVB, 47% of the total), but also sustained or treated VAs (n=18, 19%). Overall, 18% of patients had already undergone AF ablation, 13% ventricular tachycardia ablation, 3% cardiac sympathetic denervation. Finally, 95% of patients were on beta–blocker therapy and 28% were on amiodarone. Ranolazine was prescribed at an average initial dose of 535± 150 mg. The majority (54%) of patients (n=50) had a follow–up longer than 3 months (median 9 months, IQR 6–14); in 6% the drug was stopped due to intolerance and the average dose at the last FU was 641 ± 150 mg. Twenty–eight percent of patients with paroxysmal/persistent atrial arrhythmias had relapses, requiring ablation in 6%. Among patients with major VAs, 57% suffered recurrences, but only 19% required ablation (invasive in 2 cases, non–invasive in 1 case). Finally, among the patients with PVBs, none suffered major VAs or required PVB/VA ablation. Conclusions This is the largest available case–series reporting about the real–world usage of ranolazine for antiarrhythmic purposes. Our single center experience supports ranolazine’s good safety and tolerability and shows encouraging efficacy results in terms of clinical stabilization of complex patients.

THE COMPLEX WORLD OF NON CRITICAL CORONARY ARTERIES DISEASE

Abstract Background and Aim Acute coronary syndrome (ACS) with non–critical coronary arteries represents a major diagnostic, therapeutic and prognostic challenge for clinicians. The aim was to compare clinical–anamnestic characteristics and assess the prognosis of three cohorts with ACS with non–critical coronary arteries i.e. Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA), type 2 myocardial infarction (MI) and Takotsubo syndrome (TTS). Methods In this single center observational study, 18223 patients who underwent coronary angiography between 2005 and 2022 were retrospectively analyzed. The final cohort included 676 patients with initial presentation as NSTEMI (301 MINOCA, 237 type 2 MI and 138 TTS). Results The median age was 68±11, with the TTS population being the oldest (72±10, p&amp;lt;0.01), presenting greater hypotension (p&amp;lt;0.01), tachycardia (p&amp;lt;0.01), and fewer cardiovascular risk factors, such as diabetes (p&amp;lt;0.01) and hypertension (p&amp;lt;0.01). The TTS cohort had worse LVEF on admission (p&amp;lt;0.01) and on discharge (p&amp;lt;0.01) (Fig. 1). At Kaplan–Meier analysis, patients with type 2 MI were more prone to the composite endpoint, while the TTS group was less likely (p&amp;lt;0.01) (Fig. 2). In the overall cohort, ACEi/ARB therapy on admission was an independent predictor of the composite endpoint (HR: 1.58;p=0.01), while dual antiplatelet therapy (DAPT) (HR: 0.59;p=0.01) and statin (HR: 0.71;p=0.03) at discharge were protective. After stratification according to diagnosis, ACEi/ARB therapy remained a negative predictor only in the type 2 MI cohort (HR: 2.03;p=0.01) as well as beta–blocker therapy at admission in TTS (HR: 2.97;p=0.03), while statin therapy remained protective in the MINOCA (HR: 0.51;p=0.01) and DAPT therapy in the TTS group (HR: 0.21;p=0.04) at discharge. Although a substantial number of patients with all three diagnoses achieved the endpoint, the multivariable Cox regression analysis indicated that type 2 MI, in addition to older age, male gender, worse LVEF, and anemia, is an independent factor for worse outcomes (Fig. 3). Conclusions Among all cohorts, T2 MI were associated with worse outcome. The use of DAPT in TTS and Statins in the MINOCA group showed a protective role. Since the TTS population was more compromised, BB use in the ADHF phase of TTS could predict a poorer outcome as much as ACEI/ARB use at admission could be a marker of greater early LV impairment of the T2 MI cohort, which was an independent predictor for worst outcome.