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• Beta-blocker efficiency in reducing mortality after MI is well established. • This efficiency was demonstrated before the reperfusion therapy era. • Uncomplicated MI has a low risk of subsequent mortality and cardiovascular events. • It is easily identified by LVEF ≥ 40% and absence of recurrent events at 6 months. • Patients with uncomplicated MI seem ideal candidates for beta-blocker withdrawal. • This hypothesis was tested in the randomized AβYSS trial. Systematic prescription of beta-blockers after myocardial infarction remains an open question in the era of revascularization, especially for patients with uncomplicated myocardial infarction. To evaluate in a real-life registry the proportion of patients with uncomplicated myocardial infarction (preserved left ventricular ejection fraction and no cardiovascular event within the first 6 months), and to report their characteristics, outcomes and beta-blocker use. We included 1887 consecutive patients with ST-segment elevation myocardial infarction from the prospective ePARIS registry. Patients were divided into three groups: the "uncomplicated myocardial infarction" group (n = 1060), defined by a left ventricular ejection fraction ≥ 40% and a 6-month period free from cardiovascular events; the "complicated myocardial infarction" group (n = 366), defined by a left ventricular ejection fraction ≥ 40% and a recurrent cardiovascular event in the first 6 months; and the "left ventricular dysfunction" group (n = 461), defined by a left ventricular ejection fraction < 40%. During a median follow-up of 2.7 years (interquartile range 1.0–4.9 years), the "uncomplicated myocardial infarction" group was at low mortality risk compared with the "complicated myocardial infarction" group (hazard ratio 0.38, 95% confidence interval 0.25–0.58; P < 0.01) and the "left ventricular dysfunction" group (hazard ratio 0.22, 95% confidence interval 0.15–0.32; P < 0.01). Beta-blockers were prescribed at discharge predominantly in the "uncomplicated myocardial infarction" group (93%) compared with 87% in the "complicated myocardial infarction" group and 81% in the "left ventricular dysfunction" group. Beta-blockers are less prescribed in patients who may need them the most. The benefit of beta-blockers–largely prescribed in lower-risk patients–remains to be shown beyond the first 6 months for these patients with no left ventricular dysfunction and no recurrent events. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to provide data about diagnosis, treatment, and results of the patients poisoned by drugs affecting the cardiovascular system. Materials and Methods: Patients aged 18 and over who applied to the emergency department with drug poisoning affecting cardiovasculer system were included in the study. The demographic data, drugs and doses, emergency treatment and the time of development of shock or bradycardia, treatment, antidotes and invasive procedures were recorded. Results: In our study twenty-five patients, 8 (32 %) male and 17 (68 %) female, were included. At the admission, 56 % (n=14) had hypotension, 8 % (n=2) had bradycardia, at the second hour 76 % (n=19) had hypotension, 16 % (n=4) had bradycardia. Within 6 hours after admission, 80 % (n=20) patients had hypotension, 28 % (n=7) patients had bradycardia at least once. Fifty-two percent (n=13) of the patients calcium, 36 % (n=9) glukagon, 32 % (n=8) lipid, 12 % (n=3) atropine, 20 % (n=5) positive inotropes were given. Conclusion: Lipid therapy produces positive results in patients who did not improve with calcium, glucagon and fluid therapy. Patients who received calcium channel blockers experienced more cardiogenic shock and bradycardia was more common in patients receiving beta-blockers.

Abstract Aims Not all patients with heart failure with reduced ejection fraction (HFrEF) benefit equally from beta‐blockers. Previous studies suggest that myocardial strain that reflects myocardial deformation may have a better prognostic value than the left ventricular ejection fraction. We aimed to evaluate the differential effect of beta‐blockers according to the global longitudinal strain (GLS) in patients with HFrEF. Methods and results Of the 4312 patients in the Strain for Risk Assessment and Therapeutic Strategies in Patients with Acute Heart Failure registry, we included 2126 HFrEF patients whose data on beta‐blocker use and GLS were available. Patients were categorized into two groups: one group of patients had GLS ≥ 10%, and the other group had GLS 0.05). Conclusions Beta‐blocker use appears to be associated with improved survival in patients with HFrEF and GLS

Cancer neuroscience, as an emerging converging discipline, provides us with new perspectives on the interactions between the nervous system and cancer progression. As the sympathetic nervous system, in particular adrenergic signaling, plays an important role in the regulation of tumor activity at every hierarchical level of life, from the tumor cell to the tumor microenvironment, and to the tumor macroenvironment, it is highly desirable to dissect its effects. Considering the far-reaching implications of drug repurposing for antitumor drug development, such a large number of adrenergic receptor antagonists on the market has great potential as one of the means of antitumor therapy, either as primary or adjuvant therapy. Therefore, this review aims to summarize the impact of adrenergic signaling on cancer development and to assess the status and prospects of intervening in adrenergic signaling as a therapeutic tool against tumors. [ABSTRACT FROM AUTHOR]

Beta-blockers are recommended in the first 24 hours after ST-segment elevation myocardial infarction (STEMI) except in those at risk of cardiogenic shock. This retrospective cohort study aimed to assess if early beta-blocker use was associated with cardiogenic shock development in STEMI patients. Cardiogenic shock was assessed in adult patients with STEMI undergoing percutaneous coronary intervention (PCI) with guideline defined risk factors for shock (age above 70 years, systolic blood pressure below 120 mmHg, and heart rate above 120 bpm or below 60 bpm) who did or did not receive a beta-blocker within 24 hours of PCI. Multivariable logistic regression was used to assess the association between cardiogenic shock development and early beta-blocker administration. A total of 216 patients were included, 85 with early beta-blocker administration and 131 without. Patients who received an early beta-blocker versus those who did not had a median (interquartile range) age of 63 (52-71) versus 66 (54-76; P = .2260) and peak troponin of 58.3 (15.0-132.4) ng/mL versus 51.6 (16.6-139.5; P = .9884). Cardiogenic shock occurred in 4.7% (n = 4) patients with early beta-blocker use versus 12.2% (n = 16; P = .0909) without. After backward stepwise logistic regression, early beta-blocker use was not associated with cardiogenic shock (adjusted odd ratio [aOR] 0.334, 95% confidence interval (CI) 0.106-1.047; P = .0599), but those with a peak troponin over 56 ng/mL had an over three-fold increased risk of developing cardiogenic shock (aOR 3.434, 95% CI 1.191-9.902; P = .0224) regardless of beta blocker administration. Early beta-blocker administration in STEMI patients may not be associated with shock development. [ABSTRACT FROM AUTHOR]

Background: Postoperative atrial fibrillation (AF) has a complex etiology, and beta-blockers are commonly recommended for its pharmacological prevention. This study aims to assess the impact of beta-blocker therapy on postoperative AF occurrence in patients undergoing aortic valve replacement, mitral valve replacement, surgical revascularization of the myocardium, or a combination of these procedures. Methods: The study encompassed 472 patients who received aortic valve replacement, mitral valve replacement, surgical revascularization, or their combination. We evaluated the efficacy of preoperative and one-month postoperative beta-blocker administration in preventing postoperative AF, and the associated risk factors involved in the development of postoperative AF. Results: Of the total patient population, 36% experienced postoperative AF. Our study demonstrated a significant reduction in postoperative AF incidence among patients receiving beta-blocker treatment (all p-values < 0.05). Additionally, one-month post-surgery, beta-blocker treatment exerted a protective effect by maintaining the sinus rhythm (p = 0.0001). Regarding the risk factors involved in the development of postoperative AF, both age and left atrium (LA) sizeassessed pre-and postoperatively—were positively correlated with the occurrence of postoperative AF (p = 0.006). No relationship was found between leukocyte counts and AF incidence. Notably, C-reactive protein (CRP) levels were significantly elevated on the fifth postoperative day in patients with AF (p < 0.007). The duration of ischemia was significantly longer in patients with AF (p = 0.009). Conclusions: This study establishes the efficacy of perioperative beta-blocker treatment in mitigating postoperative AF. One month post-surgery, most patients under beta-blocker therapy maintained sinus rhythm, suggesting a potential long-term protective effect of beta-blockers against late-onset AF.

ABSTRACT Introduction: Classic coronary artery bypass grafting (CABG) surgery involves diastolic cardiac arrest under cardiopulmonary bypass, while off-pump CABG (OPCABG) has become widespread in recent years. Methods: 174 patients who underwent OPCABG were included in the study. Patients were divided into two groups. Group I (n=90) received ivabradine and Group M (n=84) received metoprolol before surgery until postoperative day 10. Intraoperative arrhythmias and hypotension were recorded. Postoperative atrial fibrillation (AF) and arrhythmia, mortality and morbidity rates were assessed based on the 30-day postoperative follow-up. Results: There were no significant differences in the intraoperative amount of inotropic support and red blood cell transfusion between groups (P=0.87 and P=0.31). However, the rates of intraoperative arrhythmias and hypotension were not significantly higher in Group M (P=0.317 and P=0.47). Ventricular tachycardia/ventricular fibrillation (VT/VF) was observed in 2 patients in both groups. Postoperative AF occurred in 7 patients (7.7%) in Group I and in 10 patients (11.9%) in Group M. Although there was a trend towards a higher prevalence of AF in Group M patients, this did not reach statistical significance. In addition, mortality and morbidity rates were comparable between groups.

Background: Beta-blockers are widely used for the treatment of arrhythmia, hypertension, and congestive heart failure. Major trauma causes significant blood loss and subsequent tachycardia and hypotension. Although beta-blockers may induce negative compensatory sympathetic responses to hemorrhagic shock, the effects of beta-blocker use before major trauma on posttrauma outcomes are controversial. Aim: We examined the association between the use of beta-blockers before major trauma and posttrauma outcomes using a nationwide population-based database. Methods: The data for this nationwide population-based retrospective cohort study were obtained from the National Health Insurance Research Database in Taiwan. A total of 2245 beta-blocker users were assigned to the study cohort, and another 8980 patients matched for age, sex, comorbidity, and medication use by inverse probability of treatment weighting formed the comparison cohort. The major outcome assessed was all-cause mortality during a 30-day follow-up period in major trauma patients with or without pretrauma beta-blocker use. Results: Our study included 2245 patients who used beta-blockers before major trauma. Individuals who used beta-blockers did not have a significantly higher cumulative risk of mortality than individuals who did not use beta-blockers (beta-blockers users: 17.19%, nonbeta-blockers users: 16.70%, P = 0.662). Conclusion: Pretrauma beta-blocker users did not have a higher mortality rate after a major trauma even after adjusting for several comorbidities and medications in a nationwide population database.

Background: Infantile hemangioma (IH) is the most common benign vascular tumor of infancy. Propranolol is considered first-line therapy for IH. However, it is associated with side effects. Therefore, there was a need for alternative therapy. Atenolol, a selective b1-blocker may be free from such side effects. Hence, the present study aims to develop a more accurate estimate of the safety and efficacy of atenolol compared to propranolol in the treatment of IH. Methodology: A search of various literature databases (PubMed, Embase, Ovid, Scopus, Cochrane Central, CINAHL, Web of Science, and Google Scholar) was done to identify studies which compared propranolol versus atenolol in the treatment of IH. The combined odds ratio along with corresponding 95% confidence intervals (CIs) were evaluated using a fixed-effects model. Results: A total of 300 articles were screened of which five studies including 116 patients in atenolol arm and 138 patients in the propranolol arm were analyzed. Atenolol was comparable to propranolol in terms of efficacy as no significant difference was seen between both the treatment arms in terms of hemangioma activity score (mean difference 0.25 [95% CI;‒0.21, 0.71]) and complete response (odds ratio [OR] =0.43; 95% CI; 0.17, 1.11; P = 0.08,). Atenolol therapy was better than propranolol in terms of safety, i.e., serious/potentially serious side effect, (OR = 0.11; 95% CI; 0.02, 0.51; P = 0.005) and wheezing/bronchial hyperreactivity (OR = 0.11; 95% CI; 0.02, 0.51; P = 0.005). Conclusion: The present meta-analysis provides evidence that atenolol has got a comparable efficacy and better safety profile with propranolol

BRASH (Bradycardia, Renal failure, Atrioventricular [AV]-node blocker medications, Shock, and Hyperkalemia), a novel syndrome, is a synergistic interaction between AV node blockers and hyperkalemia, resulting in bradycardia. We report a case of BRASH syndrome with marked bradycardia in a patient with End-Stage Renal Disease (ESRD) associated with synergistic interaction between mild hyperkalemia and AV node blockers. Anesthesiologists should be aware of these clinical features, in which ESRD patients with baseline mild hyperkalemia are particularly susceptible to bradycardia. This report will help in its early recognition as well as enable comprehensive and appropriate treatment strategies without further invasive therapy.

Background In patients with acute ischemic stroke, little is known regarding the frequency of abnormal ECG findings other than atrial fibrillation and their association with cardiovascular outcomes. We aim to analyze the frequency and type of abnormal ECG findings, subsequent changes in medical treatment, and their association with cardiovascular outcomes in patients with acute ischemic stroke. Methods and Results In the investigator‐initiated multicenter MonDAFIS (impact of standardized monitoring for detection of atrial fibrillation in ischemic stroke) study, 3465 patients with acute ischemic stroke or transient ischemic attack and without known atrial fibrillation were randomized 1:1 to receive Holter‐ECG for up to 7 days in‐hospital with systematic evaluation in a core cardiology laboratory (intervention group) or standard diagnostic care (control group). Outcomes included predefined abnormal ECG findings (eg, pauses, atrial fibrillation, brady‐/tachycardias), medical management in the intervention group, and combined vascular end point (recurrent stroke, myocardial infarction, major bleeds, or all‐cause death) and mortality at 24 months in both randomization groups. Predefined abnormal ECG findings were detected in 326 of 1693 (19.3%) patients in the intervention group. Twenty of these 326 patients (6.1%) received a pacemaker, and 62 of 326 (19.0%) patients had newly initiated or discontinued β‐blocker medication. Discontinuation of β‐blockers was associated with a higher death rate in the control group than in the intervention group during 24 months after enrollment (adjusted hazard ratio, 11.0 [95% CI, 2.4–50.4]; P=0.025 for interaction). Conclusions Systematic in‐hospital Holter ECG reveals abnormal findings in 1 of 5 patients with acute stroke, and mortality was lower at 24 months in patients with systematic ECG recording in the hospital. Further studies are needed to determine the potential impact of medical management of abnormal ECG findings. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02204267.

BackgroundSotalol is a commonly used antiarrhythmic drug that may alter ventricular function.ObjectiveTo determine the effect of sotalol on echocardiographic indices of ventricular systolic function in dogs with ventricular arrhythmias.AnimalsThirty-five client-owned dogs with ventricular arrhythmias.MethodsDogs with ventricular arrhythmias (n = 27) had an echocardiogram and 5-minute ECG performed at baseline and 2-4 hours post-sotalol (2-2.5 mg/kg PO once). Eight additional dogs underwent the same protocol but did not receive sotalol (within-day variability controls). Left ventricular (LV) internal dimension at end-systole normalized to bodyweight (LVIDs_N), LV ejection fraction (LV EF), LV shortening area, LV fractional shortening, tricuspid annular plane systolic excursion (TAPSE), and right ventricular systolic myocardial velocity were evaluated as indices of systolic function.ResultsAll indices except TAPSE had mild decreases in systolic function post-sotalol (all P ≤ .0007) compared with baseline but only the percent change in LVIDs_N and LV EF were significantly (P ≤ .0079) different from the percent change of the same indices in control dogs. Sinus heart rate, ventricular premature complexes/5-minutes, and arrhythmia grade also were decreased post-sotalol (all P ≤ .01) compared with baseline when assessed by a 5-minutes ECG. No dog experienced an adverse event post-sotalol, including dogs with systolic dysfunction or atrial enlargement.Conclusions and clinical importanceA single dose of sotalol may cause a mild decrease in LV systolic function in dogs with ventricular arrhythmias. Sotalol appears to be well tolerated, even in dogs with atrial enlargement or systolic dysfunction.

Thrombocytopenia is a commonly encountered complication of hospitalized patients, and can be caused by many factors including infections, surgery, and medications. Drug-induced thrombocytopenia (DITP) should be considered when a patient presents with an unexpected occurrence of thrombocytopenia. Many drugs can induce thrombocytopenia either as a direct effect on thrombopoiesis within the bone marrow or by drug-dependent antibody-mediated destruction of platelets within the circulation. We present the case of a 44-year-old female who presented with 2 weeks of nausea, vomiting, and headaches occurring with her hemodialysis sessions. On admission she was found to be thrombocytopenic with a platelet count of 35 K/µL. Her last known normal platelet count was 299 K/µL from 2 months prior. A thorough work up of her thrombocytopenia was found to be unremarkable. Her newly started carvedilol was thought to be the most likely cause based on the rapid platelet recovery upon drug discontinuation and negative workup of other potential causes. [ABSTRACT FROM AUTHOR]

Purpose: Atrial fibrillation (Afib) with rapid ventricular response (RVR) is acutely treated with intravenous push (IVP) metoprolol (MET) or diltiazem (DIL). In heart failure (HF) patients, diltiazem is not recommended due to negative inotropic effects. Studies comparing the treatment of atrial fibrillation often exclude HF. Hirschy et al. evaluated HF patients with concomitant Afib with RVR who received IVP metoprolol or diltiazem to determine their effectiveness and safety. They found similar safety and effectiveness outcomes between the two groups.Methods: This retrospective, IRB-approved study evaluated patients presenting to the emergency center (EC) with Afib with RVR and HF from January 1, 2018 to July 31, 2021. Included patients were 18 years of age or older, received IVP metoprolol or diltiazem in the EC, and had a recorded baseline ejection fraction (EF). The primary effectiveness outcome was successful heart rate (HR) control 30 min after treatment with either IVP metoprolol or diltiazem, which was defined as HR <100 beats per minute (bpm). Secondary effectiveness outcomes included HR control 60 min post-IVP and at EC discharge or transfer and HR reduction >20% at 30 min after IVP, 60 min after IVP, and at time of discharge or transfer. Other secondary outcomes included the time to adequate HR control, the total dose of IVP metoprolol or diltiazem given, any additional rate-controlling agents given, and crossover between metoprolol and diltiazem. Safety outcomes included bradycardia, hypotension, shortness of breath, increased oxygen requirements, change in EF, acute kidney injury or renal replacement therapy.Results: Of 2580 evaluated, 193 patients were included (134 DIL vs. 59 MET) with age 73.3 ± 12.2 years, 63% female. The average EF was 48.2 ± 14.2% and 30% of patients had heart failure with reduced ejection fraction (HFrEF) while 64% had heart failure with preserved ejection fraction (HFpEF). Effective heart rate control 30 min post-IVP was not different between the two groups (55% DIL vs. 41% MET, p = 0.063). DIL effectively controlled HR quicker than MET (13 [9, 125] DIL vs. 27 [5, 50] MET, min, p = 0.009). DIL resulted in greater HR reductions at 30 min (33.2 ± 25.4 DIL vs. 19.7 ± 19.7 MET, bpm, p < 0.001) and at 60 min (31 ± 23.5 DIL vs. 19.6 ± 19.1 MET, bpm, p = 0.002). DIL also more frequently resulted in a HR reduction of 20% or greater at 30 min (63% DIL vs. 27% MET, p < 0.001), 60 min post-IVP (59% DIL vs. 41% MET, p = 0.019), and at time of patient discharge or transfer from the EC (70% DIL vs. 49% MET, p = 0.005). No differences in safety outcomes were identified.Conclusion: Acute management of patients with Afib with RVR and HF is challenging. While successful rate control at 30 min was not significantly different between diltiazem and metoprolol, IVP diltiazem reduced HR more quickly and reduced HR by 20% or greater more frequently than IVP metoprolol with no safety outcome differences. Further studies are needed to evaluate diltiazem's safety in patients with Afib and HF. [ABSTRACT FROM AUTHOR]

In patients without heart failure or left ventricular systolic dysfunction after acute coronary syndrome in the contemporary percutaneous coronary intervention (PCI) era: • beta-blocker therapy may reduce the risk of all-cause death; • no differences existed in other outcomes, which may be due to limited studies; • beta-blocker may still be beneficial in the PCI era. Beta-blockers are the standard treatment for acute coronary syndrome (ACS) based on evidence from the prethrombolytic era. We sought to examine the effect of beta-blocker treatment on patients without heart failure or left ventricular systolic dysfunction after ACS in the contemporary percutaneous coronary intervention (PCI) era. We systematically searched PubMed, Web of Science, Cochrane Library, ClinicalTrials.gov and Google Scholar for studies comparing beta-blockers versus no beta-blockers in ACS patients in the contemporary PCI era. The primary outcome was all-cause death. Pooling unadjusted and multivariable adjusted results were calculated under random-effects models. Data from 15 studies (n = 205,672), including 1 randomized trial, were analysed. Compared with no beta-blockers, beta-blocker therapy at discharge may reduce the risk of all-cause death (odds ratio [OR] 0.66, 95% confidence interval [CI]: 0.50–0.86; I2 = 81.9%). Subgroup analysis according to single or multicentre studies indicated similar results. Prospective studies suggested that all-cause death was less common in the beta-blocker group. After multivariable adjustment, a lower risk of all-cause death was still observed with beta-blockers (OR: 0.74, 95% CI: 0.59–0.94; I2 = 40.1%). No differences existed in major adverse cardiovascular events (MACE), cardiac death, myocardial infarction, heart failure, revascularization or stroke, before and after multivariable adjustment. In patients without heart failure or left ventricular systolic dysfunction after ACS in the contemporary PCI era, beta-blocker therapy may still be beneficial due to a potential reduced risk of all-cause death. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular medications are vital for the secondary prevention of coronary arterial disease (CAD). However, the effect of cardiovascular medication may depend on the optimal adherence of the patients. This meta‐analysis aims to determine the magnitude of adherence to vascular medications that influences the absolute and relative risks (RRs) of mortality in patients with CAD in real‐world settings. Methods: The Cochrane Library, PubMed, and EMBASE databases were searched through March 1, 2022. Prospective studies reporting association as RR and 95% confidence interval between cardiovascular medication adherence and any cardiovascular events and/or all‐cause mortality in patients with CAD were included. A one‐stage robust error meta‐regression method was used to summarize the dose‐specific relationships. Results: A total of 18 studies were included. There is a significant inverse linear association between cardiovascular medication adherence and cardiovascular events (pnonlinearity =.68) or mortality (pnonlinearity =.82). The exposure‐effect analysis showed that an improvement of 20% cardiovascular medication adherence was associated with 8% or 12% lower risk of any cardiovascular events or mortality, respectively. In subgroup analysis, the benefit was observed in adherence of stain (RR: 0.90, for cardiovascular events, RR: 0.85, for mortality), angiotensin‐converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARB)(RR: 0.90, for mortality), and antiplatelet agent (RR: 0.89 for mortality) but not in beta‐blocker (RR: 0.90, p =.14, for cardiovascular events, RR: 0.97, p =.32 for mortality). Estimated absolute differences per 1 million individuals per year for mortality associated with 20% improvement were 175 cases for statin, 129 cases for antiplatelet, and 117 cases for ACEI/ARB. Conclusion: Evidence from the real word showed poor adherence to vascular medications contributes to a considerable proportion of all cardiovascular disease events and mortality in patients with CAD. [ABSTRACT FROM AUTHOR]

Two cases of pyogenic granulomas in burned skin were presented, a 17‐month‐old boy and a 7‐year‐old girl, being given oral propranolol and topical timolol. Both cases showed lesions improvement with no adverse effects, suggesting that beta‐blocker therapy may have a positive impact on the treatment of pyogenic granuloma after burns. [ABSTRACT FROM AUTHOR]

Background: Beta-blockers are widely used for the treatment of arrhythmia, hypertension, and congestive heart failure. Major trauma causes significant blood loss and subsequent tachycardia and hypotension. Although beta-blockers may induce negative compensatory sympathetic responses to hemorrhagic shock, the effects of beta-blocker use before major trauma on posttrauma outcomes are controversial. Aim: We examined the association between the use of beta-blockers before major trauma and posttrauma outcomes using a nationwide population-based database. Methods: The data for this nationwide population-based retrospective cohort study were obtained from the National Health Insurance Research Database in Taiwan. A total of 2245 beta-blocker users were assigned to the study cohort, and another 8980 patients matched for age, sex, comorbidity, and medication use by inverse probability of treatment weighting formed the comparison cohort. The major outcome assessed was all-cause mortality during a 30-day follow-up period in major trauma patients with or without pretrauma beta-blocker use. Results: Our study included 2245 patients who used beta-blockers before major trauma. Individuals who used beta-blockers did not have a significantly higher cumulative risk of mortality than individuals who did not use beta-blockers (beta-blockers users: 17.19%, nonbeta-blockers users: 16.70%, P = 0.662). Conclusion: Pretrauma beta-blocker users did not have a higher mortality rate after a major trauma even after adjusting for several comorbidities and medications in a nationwide population database. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) is a major concern in heart failure (HF) due its high prevalence as well as its negative impact on the quality of life, this condition being usually unrecognized and thus untreated. A number of possible causes might contribute to the above mentioned tight association, i.e., shared risk factors, comorbidities and several physiologic HF abnormalities such as impaired exercise tolerance, psychogenic factors and neurohumoral, metabolic and vascular changes. Medications have been blamed for playing also a pivotal role in the ED occurrence and, particularly, the β-blockers. Remarkably, the underlying mechanisms have not been fully identified. All the available scientific literature dealing with this topic derives from studies not addressing this issue in HF, but in other settings, (e.g., arterial hypertension) and are also characterized by important methodological flaws. Thus, given the solid evidences arguing in favor of β-blockers in HF in terms of morbidity, mortality and quality of life, β-blockers at the maximal tolerated dosage in this patients' category should be recommended, regardless of ED. However, the ED-related issues should not be neglected, and adequate psychological counseling and management should be provided, pursuing the correction of risk factors, the choice of more suitable medications and, in selected cases, adopting specific drugs or devices. The purpose of this narrative review is to highlight the close relationship between ED and HF and, specifically, to focus on a possible β-blockers' role in determining or, at least, worsening this condition. [ABSTRACT FROM AUTHOR]

Introduction: Classic coronary artery bypass grafting (CABG) surgery involves diastolic cardiac arrest under cardiopulmonary bypass, while off-pump CABG (OPCABG) has become widespread in recent years. Methods: 174 patients who underwent OPCABG were included in the study. Patients were divided into two groups. Group I (n=90) received ivabradine and Group M (n=84) received metoprolol before surgery until postoperative day 10. Intraoperative arrhythmias and hypotension were recorded. Postoperative atrial fibrillation (AF) and arrhythmia, mortality and morbidity rates were assessed based on the 30-day postoperative follow-up. Results: There were no significant differences in the intraoperative amount of inotropic support and red blood cell transfusion between groups (P=0.87 and P=0.31). However, the rates of intraoperative arrhythmias and hypotension were not significantly higher in Group M (P=0.317 and P=0.47). Ventricular tachycardia/ventricular fibrillation (VT/VF) was observed in 2 patients in both groups. Postoperative AF occurred in 7 patients (7.7%) in Group I and in 10 patients (11.9%) in Group M. Although there was a trend towards a higher prevalence of AF in Group M patients, this did not reach statistical significance. In addition, mortality and morbidity rates were comparable between groups. [ABSTRACT FROM AUTHOR]

A 13-year-old girl with Jervell and Lange-Nielsen syndrome associated congenital long QT syndrome (LQTS) and central deafness was admitted for generalized seizures. LQTS had been diagnosed after birth and confirmed at genetic testing. β-blocker treatment was immediately started. Despite this, since the age of 12 months, recurrent cerebral seizures occurred leading to the diagnosis of epilepsy. Anti-convulsive therapy was initiated but without success. At the last admission, nadolol dosage seemed infratherapeutic. Considering malignant ventricular arrhythmias as the cause of seizures, the β-blocker dosage was adjusted to weight and levels of magnesium and potassium optimized. Furthermore, the patient received an implantable Medtronic Reveal LINQ Recorder®. Since then, the adolescent has been asymptomatic with no arrhythmia documented. LQTS is due to one or more mutations of genes coding for ion channels. It may induce malignant ventricular arrhythmias and is a major cause of sudden cardiac death in children. Generalized cerebral seizures are extra-cardiac manifestations caused by decreased cerebral perfusion during ventricular arrhythmia. They are commonly misinterpreted as manifestations of epilepsy. For any patient with known or unknown LQTS who presents seizures with resistance to anti-convulsive therapy, a cardiac electrophysiological investigation should be performed promptly to ensure etiological diagnosis and optimize treatment. [ABSTRACT FROM AUTHOR]

Aims: The optimal treatment for severe aortic valve disease complicated with moderate function mitral regurgitation (FMR) remains controversial. Although isolated surgical aortic valve replacement (SAVR) is reasonable, previous studies also show that moderate FMR might deteriorate after surgical treatment and result in poorer prognosis. Because the left ventricular remodelling plays a critical role in the development of FMR, these patients might potentially benefit from the administration of β‐blocker (BB). Unfortunately, relevant clinical evidence is lacking. This study aimed to investigate the impact of post‐operative administration of BB on the outcomes of moderate FMR patients undergoing isolated SAVR. Methods: In this single‐centre cohort study, patients who underwent isolated SAVR and complicated with pre‐operative moderate FMR during 2010 and 2019 at our centre were retrospectively recruited. Patients were divided into two groups according to postoperative administration of BB (BB group vs. control group). The cumulative survival rates were calculated using the Kaplan–Meier method and tested by the log‐rank test, followed by inverse probability treatment weighting (IPTW) analysis to further control the between‐group imbalances. The primary outcome was the major adverse cardiovascular and cerebrovascular events (MACCE), a composite endpoint of all‐cause death, repeat heart valve surgery, non‐fatal myocardial infarction, stroke, and hospitalization for heart failure. Results: A total of 165 patients were enrolled, 57 (34.6%) of whom were female, and the mean age was 59.2 ± 12.2 years. Eighty (48.5%) patients received post‐operative BB therapy. The median follow‐up time was 18.4 months. The administration of BB was not associated with lower risk of MACCE [hazard ratio (HR): 0.68, 95% confidence interval (CI): 0.29–1.62, P = 0.388] or all‐cause death (HR: 1.03, 95% CI: 0.30–0.56, P = 0.967). In the IPTW dataset, the total number of patients were 326.89, and the outcomes regarding the risk of MACCE (HR: 0.79, 95% CI: 0.31–1.97, P = 0.607) and all‐cause death (HR: 1.33, 95% CI:0.35–5.05, P = 0.674) were in line with the unmatched analysis. The follow‐up echocardiographic results were available for 72.2% of the overall cohort, and the use of BB was observed to be associated with higher improvement rate of follow‐up FMR according to the IPTW analysis (92.2% vs. 98.3%, P = 0.033). Conclusions: The administration of BB after SAVR was not associated with lower risk of MACCE for patients of severe aortic valve disease complicated with moderate FMR, but was potentially beneficial for improving FMR. [ABSTRACT FROM AUTHOR]

Aims: Among patients with myocardial infarction (MI) with preserved left ventricular ejection fraction (LVEF), the REDUCE-AMI trial did not demonstrate a benefit of beta-blocker vs. no beta-blocker treatment on all-cause mortality and recurrent myocardial infarction. The aim of this pre-specified sub-study was to investigate effects of beta-blockers on self-reported symptoms of anxiety and depression., Methods and Results: In this parallel-group, open-label, registry-based randomized trial, assessments with the Hospital Anxiety and Depression Scale were obtained at hospitalization and two follow-up points (6-10 weeks and 12-14 months) after MI. Analyses were based on the intention-to-treat principle using linear mixed models, calculating both short- and long-term effects. From August 2018 through June 2022, 806 patients were enrolled. At baseline, 27% of patients were possible cases of anxiety (m, 5.6; SD, 3.9) and 14% were possible cases of depression (m, 3.9; SD, 3.2). Beta-blocker treatment had a negative effect on depressive symptoms at both follow-ups 1 (β = 0.48; 95% CI 09-0.86; P = 0.015) and 2 (β = 0.41; 95% CI = 0.01-0.81; P = 0.047), but no effect on anxiety., Conclusion: Beta-blocker treatment led to a modest increase in depressive symptoms among MI patients with preserved LVEF. This observed effect was most pronounced in individuals with prior beta-blocker treatment. In routine initiation and continuation of beta-blocker treatment, a risk of slightly increased depressive symptoms should be considered., Competing Interests: Conflict of interest: C.H. reports consulting fees from AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Coal Life, and Pharmacosmos and lecture fees from Amarin and Bayer. R.H. reports lecture fees to institution from AstraZeneca, Pfizer, and BMS. T.J. reports consulting fees from Amgen. P.K. reports lecture fees from Vifor Pharma, AstraZeneca, and Boehringer Ingelheim and as a member of the Advisory Board from Pharmacosmos and AstraZeneca and Novartis. T.Y. is a member of the executive committee in SWEDEHEART on Acute Coronary Care (RiksHIA)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Norepinephrine (NE) modulates cognitive function, arousal, attention, and responses to novelty and stress, and also regulates neuroinflammation. We previously demonstrated behavioral and immunomodulatory effects of beta-adrenergic pharmacology in mouse models of Alzheimer's disease (AD). The current studies were designed to block noradrenergic signaling in 5XFAD mice through 1) chemogenetic inhibition of the locus coeruleus (LC), 2) pharmacologic blocking of β-adrenergic receptors, and 3) conditional deletion of β1- or β2-adrenergic receptors (adrb1 or adrb2) in microglia. First, brain-wide AD pathology was mapped in 3D by imaging immunolabeled, cleared 5XFAD brains to assess the overlap between Aβ pathology, reactive microglia, and the loss of tyrosine hydroxylase (TH) expression in the catecholaminergic system. To examine the effects of inhibiting the LC NE system in the 5XFAD model, inhibitory (Gi) DREADD receptors were expressed specifically in LC NE neurons. LC NE neurons were chronically inhibited through the subcutaneous pump administration of the DREADD agonist clozapine-N-oxide (CNO). Plasma and brains were collected for assessment of neuroinflammation and pathology. A separate cohort of 5XFAD mice was chronically dosed with the beta-adrenergic antagonist propranolol or vehicle and evaluated for behavior, as well as post-mortem neuroinflammation and pathology. Finally, we used 5XFAD mice with conditional deletion of either adrb1 or adrb2 in microglia to assess neuroinflammation and pathology mediated by β-adrenergic signaling. Using iDISCO, light sheet fluorescence microscopy, and novel analyses, we detected widespread microgliosis and amyloid pathology, along with modest TH downregulation in fibers across multiple brain regions, in contrast to the spatially limited TH downregulation observed in neurons. Both chemogenetic inhibition of LC adrenergic signaling and pharmacological inhibition of beta-adrenergic receptors potentiated neuroinflammation without altering amyloid beta pathology. Conditional deletion of adrb1 in microglia did not affect neuroinflammation. Conditional deletion of adrb2 in microglia attenuated inflammation and pathology in females but had no effect in males. Overall, these data support previous observations demonstrating the immunomodulatory effects of beta-adrenergic signaling in the pathophysiology of brain disorders and suggest that adrenergic receptors on cell types other than microglia, such as astrocytes, may predominantly mediate the disease-modifying effects of β-adrenergic agonists in the brain., Competing Interests: MS is a shareholder and founder of CuraSen Therapeutics, a company developing adrenergic drugs for the treatment of neurodegenerative disease. AKE is a shareholder of CuraSen Therapeutics. However, this work was initiated and carried out independently from CuraSen Therapeutics and was not designed, initiated, or funded by CuraSen Therapeutics. BDH is on the scientific advisory boards of Journey Clinical and Osmind, and is a paid consultant to Arcadia Medicine, Inc.

Aims: The benefit of long-term beta-blocker therapy after acute coronary syndromes (ACS) without heart failure in the reperfusion era is uncertain. Two recent randomized trials found conflicting results. The present study assessed the safety of beta-blocker discontinuation within 12 months following ACS with LVEF ≥40%., Methods: In a multicentre prospective real-world cohort (N=3,762) of patients hospitalized for ACS, patients with LVEF ≥40% and beta-blockers at discharge were included. Patients who continued beta-blockers at one year were compared with those who discontinued beta-blockers within 12 months post-ACS using target trial emulation and inverse probability weighting over an additional four-year follow-up. The primary endpoint was major adverse cardiovascular events (MACE), a composite of four-year cardiovascular death, myocardial infarction, stroke, transient ischemic attack, unplanned coronary revascularization, or unstable angina hospitalization., Results: Of 2,077 patients, 1,758 (85%) continued beta-blockers and 319 (15%) had discontinued beta-blockers at one year. The risk of primary endpoint was similar in both groups (14.1% versus 14.3% with beta-blocker discontinuation versus continuation; adjusted hazard ratio [aHR]=0.98; 95% confidence interval, 0.72-1.34, P=0.91). Subgroup analysis suggested a higher risk of primary endpoint with beta-blocker discontinuation after STEMI (aHR=1.46 [0.99-2.16]) compared to NSTEMI (aHR=0.70 [0.40-1.22], Pinteraction=0.033), whereas there was no interaction with LVEF (Pinteraction=0.68)., Conclusions: Beta-blocker discontinuation within 12 months following ACS with LVEF ≥40% was not associated with an increased risk of MACE compared to long-term beta-blocker therapy. Subgroup analysis suggested potential risk in STEMI patients. Discontinuing beta-blockers 12 months after ACS appears safe in patients with LVEF ≥40%, particularly after NSTEMI., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To assess the effect of propranolol on time to delivery among patients undergoing induction or augmentation of labor., Data Sources: PubMed, Scopus, Cochrane Library, ClinicalTrials.gov, and CINAHL (EBSCO) were searched from inception to December 2023., Study Eligibility Criteria: Randomized controlled trials (RCTs) that examined the impact of propranolol on time to delivery among patients undergoing induction or augmentation of labor were included. RCTs that included stillbirth before randomization, non-randomized trials, observational, cohort, case control, or studies in which the control group included an intervention other than standard care were excluded., Study Appraisal and Synthesis Methods: Primary outcome was time to delivery after administration of propranolol among patients undergoing induction or augmentation of labor. The summary measures were reported as summary mean difference (MD) or relative risk with 95% confidence interval (CI)., Results: Nine RCTs including 1,182 patients were included in this meta-analysis. Five studies investigated the effect of propranolol among patients undergoing induction of labor (IOL) and demonstrated a significant decrease in time to delivery (MD, -91.5 minutes, 95% CI -110.6 to -72.4). Four studies investigated the effect of propranolol among patients undergoing augmentation of labor and showed no significant decrease in time to delivery (MD, -2.98 minutes, 95% CI -21.6 to 15.6). Our pooled analysis demonstrated that the use of propranolol in IOL and augmentation was associated with a decrease in time to delivery from administration of propranolol compared to placebo (mean difference, -46.15 minutes, 95% CI -59.48 to -32.81). The meta-analysis found no increased risk of PPH, blood transfusion, cesarean delivery rates, or NICU admission with the use of propranolol during labor., Conclusion: The use of propranolol during induction of labor shortens overall time to delivery by about 91 minutes and did not significantly decrease time to delivery in those undergoing augmentation of labor., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Abstract Background The use of preoperative beta-blockers has been accepted as a quality standard for patients undergoing coronary artery bypass graft (CABG) surgery. However, conflicting results from recent studies have raised questions concerning the effectiveness of this quality metric. We sought to determine the influence of preoperative beta-blocker administration before CABG in patients with left ventricular dysfunction. Methods The authors analyzed all cases of isolated CABGs in patients with left ventricular ejection fraction less than 50%, performed between 2012 January and 2017 June, at 94 centres recorded in the China Heart Failure Surgery Registry database. In addition to the use of multivariate regression models, a 1–1 propensity scores matched analysis was performed. Results Of 6116 eligible patients, 61.7% received a preoperative beta-blocker. No difference in operative mortality was found between two cohorts (3.7% for the non-beta-blockers group vs. 3.0% for the beta-blocker group; adjusted odds ratio [OR] 0.82 [95% CI 0.58–1.15]). Few differences in the incidence of other postoperative clinical end points were observed as a function of preoperative beta-blockers except in stroke (0.7% for the non-beta-blocker group vs. 0.3 for the beta-blocker group; adjusted OR 0.39 [95% CI 0.16–0.96]). Results of propensity-matched analyses were broadly consistent. Conclusions In this study, the administration of beta-blockers before CABG was not associated with improved operative mortality and complications except the incidence of postoperative stroke in patients with left ventricular dysfunction. A more granular quality metric which would guide the use of beta-blockers should be developed.

Abstract Aims The number of patients with both chronic obstructive pulmonary disease (COPD) and heart failure (HF) is increasing in Asia, and these conditions often coexist. We previously revealed a tendency of beta‐blocker underuse among patients with HF with reduced ejection fraction (HFrEF) and COPD in Asian countries other than Japan. Here, we evaluated the impact of cardio‐selective beta‐blocker use on the long‐term outcomes of patients with HF and COPD. Methods and results Among the 5232 patients with HFrEF (left ventricular ejection fraction of

Abstract Two cases of pyogenic granulomas in burned skin were presented, a 17‐month‐old boy and a 7‐year‐old girl, being given oral propranolol and topical timolol. Both cases showed lesions improvement with no adverse effects, suggesting that beta‐blocker therapy may have a positive impact on the treatment of pyogenic granuloma after burns.

Background: Beta-blocker (BB) and calcium channel blocker (CCB) antihypertensive drugs are commonly used in pregnancy. However, data on their relative impact on maternal and foetal outcomes are limited. We leveraged genetic variants mimicking BB and CCB antihypertensive drugs to investigate their effects on risk of pre-eclampsia, gestational diabetes and birthweight using the Mendelian randomization paradigm.Methods: Genetic association estimates for systolic blood pressure (SBP) were extracted from summary data of a genome-wide association study (GWAS) on 757,601 participants. Uncorrelated single-nucleotide polymorphisms (SNPs) associated with SBP (p < 5 × 10-8) in BB and CCB drug target gene regions were selected as proxies for drug target perturbation. Genetic association estimates for the outcomes were extracted from GWASs on 4743 cases and 136,325 controls (women without a hypertensive disorder in pregnancy) for pre-eclampsia or eclampsia, 7676 cases and 130,424 controls (women without any pregnancy-related morbidity) for gestational diabetes, and 155,202 women (who have given birth at least once) for birthweight of the first child. All studies were in European ancestry populations. Mendelian randomization estimates were generated using the two-sample inverse-variance weighted model.Results: Although not reaching the conventional threshold for statistical significance, genetically-proxied BB was associated with reduced risk of pre-eclampsia (OR per 10 mmHg SBP reduction 0.27, 95%CI 0.06-1.19, p = 0.08) and increased risk of gestational diabetes (OR per 10 mmHg SBP reduction 2.01, 95%CI 0.91-4.42, p = 0.08), and significantly associated with lower birthweight of first child (beta per 10 mmHg SBP reduction - 0.27, 95%CI - 0.39 to - 0.15, p = 1.90 × 10-5). Genetically-proxied CCB was associated with reduced risk of pre-eclampsia and eclampsia (OR 0.62, 95%CI 0.43-0.89, p = 9.33 × 10-3), and was not associated with gestational diabetes (OR 1.05, 95% CI 0.76-1.45, p = 0.76) or changes in birthweight of first child (beta per 10 mmHg SBP reduction 0.02, 95%CI - 0.04-0.07, p = 0.54).Conclusions: While BB and CCB antihypertensive drugs may both be efficacious for lowering blood pressure in pregnancy, this genetic evidence suggests that BB use may lower birthweight. Conversely, CCB use may reduce risk of pre-eclampsia and eclampsia without impacting gestational diabetes risk or birthweight. These data support further study on the effects of BBs on birthweight. [ABSTRACT FROM AUTHOR]

Background: Clinical guidelines recommend titration of angiotensin converting enzyme inhibitors (ACEi) and beta-blockers among patients with heart failure with reduced ejection fraction (HFrEF) to maximally tolerated doses. Patient characteristics associated with dose titration and clinical outcomes subsequent to dose titration remain poorly characterized.Methods: Among 1999 ambulatory patients with chronic HFrEF in the HF-ACTION trial, use and dosing of ACEi and evidence-based beta-blockers were examined at baseline and 6-month follow-up. Multivariable logistic regression models were used to assess factors associated with dose escalation (medication initation or dosing increase) or dose de-escalation (medication discontinuation or dosing decrease). Cox proportional hazard regression models were used to examine associations between dose trajectory group (stable target, stable sub-target, dose escalation, and dose de-escalation) and subsequent mortality and hospitalization outcomes.Results: For both ACEi and beta-blockers, hospitalization for heart failure in the 6 months prior to enrollment (odds ratio [OR] 2.32 [95% confidence interval 1.58-3.42]) for ACEi; 1.42 [1.05-1.9] for beta-blockers) and higher systolic blood pressure (OR 1.01 [1.00-1.03] per 1 mmHg increase for ACEi; 1.01 [1.00-1.02] for beta-blockers) were associated with dose escalation. Hospitalization 6 months prior to enrollment for any cause (including HF or non-HF causes) was associated with dose de-escalation (OR 1.60 [1.14-2.25] for ACEi; 1.67 [1.20-2.33] for beta-blockers). After adjustment for patient characteristics, compared with stable target dosing, dose de-escalation of either medication was associated with greater all-cause mortality (adjusted hazard ratio [aHR] 1.64 [1.11-2.42] for ACEi; 1.62 [1.04-2.53] for beta-blockers). Compared with stable target dosing, both dose de-escalation (aHR 1.98 [1.36-2.87]) and stable sub-target dosing (aHR 1.49 [1.18-1.87]) of beta-blockers were associated with greater cardiovascular mortality or hospitalization for heart failure.Conclusions: Among outpatients with chronic HFrEF, patient characteristics including recent hospitalization status and blood pressure were associated with odds of subsequent escalation and de-escalation of ACEi and beta-blocker therapy. Compared with patients receiving guildeline-recommended target doses, dose de-escalation of either medication and sub-target dosing of beta-blockers were associated with greater morbidity and mortality over long-term follow-up. [ABSTRACT FROM AUTHOR]

The development of hypertension and heart failure is correlated with the hyperactivation of the sympathetic nervous system. Beta-blockers are often considered a good therapeutic option in such clinical scenarios. However, the choice of β-blocker is a concern because of certain aspects like associated metabolic disturbances with their usage. Metoprolol has been reported to have the potential to alleviate sympathetic overdrive in patients with hypertension and heart failure. S-Metoprolol is the chirally pure β-blocker with favorable pharmacological features, improved safety profile, and allied clinical advantages versus racemic metoprolol; given this, can it be an effective therapeutic option against sympathetic overdrive in patients with hypertension and/or heart failure is not fully recognized yet. In this review, we attempted to discuss the current facts around sympathetic overdrive linked with hypertension as well as heart failure and pertaining pharmacological intervention with a focus on β-blockers in these clinical situations with an emphasis on the likely beneficial role of S-metoprolol. [ABSTRACT FROM AUTHOR]

Introduction: Beta-blockers are recommended by the European Society of Cardiology as first-line antianginal therapy for reducing heart rate (HR) and symptoms in patients with chronic coronary syndrome, despite a lack of data showing superiority to other antianginal agents. Most patients with angina pectoris require combination therapy to manage symptoms, with a second-line agent chosen to manage the predominant cardiovascular problem. Ivabradine, a selective sinus node If channel inhibitor shown to reduce HR and protect against anginal symptoms, has previously demonstrated noninferior anti-ischaemic and antianginal efficacy to beta-blockers.Methods: This systematic review and meta-analysis assessed the efficacy and safety of ivabradine in patients with stable angina pectoris who remained symptomatic despite receiving beta-blockers. Keyword searches of PubMed, The Cochrane Central Library Register, ClinicalTrials.gov, The World Health Organization International Clinical Trials Registry Platform (ICTRP) and Google Scholar identified studies comparing ivabradine plus beta-blockers with placebo or other first- or second-line antianginal agents in patients with stable angina pectoris. No date limits or language restrictions were applied. Outcomes were evaluated after 1 and 4 months of treatment, including changes in HR, angina attacks, use of short-acting nitrates, quality of life and safety. Risk of bias was evaluated on the basis of recommendations of the Cochrane Handbook for Systematic Reviews of Interventions.Results: Seven relevant studies were identified (N = 6821). Ivabradine plus a beta-blocker consistently reduced HR, anginal symptoms and short-acting nitrate consumption within 1 month of initiating therapy, with continued reductions for up to 4 months. Furthermore, ivabradine plus beta-blocker therapy was well tolerated, with bradycardia rarely reported (0.1% of patients overall). This study is limited by the inclusion of only two randomised studies, which may lead to result interpretation bias.Conclusions: Ivabradine may be valuable for tailoring early antianginal treatment when used in combination with beta-blockers for chronic stable angina inadequately controlled by beta-blockers. [ABSTRACT FROM AUTHOR]

Aim: We aimed to investigate French pharmacovigilance data. The objective was to characterize psoriatic conditions that occurred after beta‐blocker (BB) exposure and bring to light a possible pharmacovigilance signal. Methods: Spontaneous reports of psoriatic conditions recorded in the French National Pharmacovigilance Database (FPVD) between 1985 and 2019 were extracted. We performed a retrospective, descriptive analysis of reports linked to BB exposure. Association between psoriasis risk and BB exposure was assessed using a case/noncase study. Results: Two hundred and twenty‐five reports of psoriatic conditions after BB exposure were recorded in the FPVD during the study period. Both cardioselective and noncardioselective, topical and systemic BBs are involved. Therapeutic indication of BB was mainly hypertension. Mean time to onset was 5 months and outcome was favourable in 68% after BB discontinuation. These features were concordant with those of literature reports. The reporting odds ratio (ROR) was 8.95 (95% confidence interval 7.75‐10.33). Conclusion: We highlighted a statistically significant disproportionality which constitutes a pharmacovigilance signal. Psoriasis risk with BBs is a class effect. Increasing surveillance during the first year of BB exposure is needed. [ABSTRACT FROM AUTHOR]

Recent observational studies linked β-adrenergic receptor blocker use with improved survival in patients with several cancer types, but there is no information on the potential effects of β-blockers in patients with bladder cancer. Literature from pre-clinical studies is also limited, but urothelial cancer can exhibit significant overexpression of β-adrenergic receptors relative to normal urothelial tissue, suggesting that urothelial cancer may benefit from β-blockade therapy. We thus aimed to explore the possible association between β-blocker use and bladder cancer-specific mortality (BCSM) among patients with urothelial bladder cancer. Patients diagnosed during 2006–2014 and identified from the Swedish Cancer Register (n = 16,669) were followed until 31 December 2015. Cox regression was used to evaluate the association of β-blockers dispensed within 90 days prior to cancer diagnosis with BCSM (primary outcome) and all-cause mortality, while controlling for socio-demographic factors, tumor characteristics, comorbidity, other medications and surgical procedures. Hazard ratios (HR) with 95% confidence intervals (CI) were reported. Overall, β-blocker use was associated with lower BCSM [HR 0.88 (95%CI 0.81–0.96)]. Especially use of nonselective β-blockers showed a clear inverse association in comparison with both nonuse [0.66 (0.50–0.86)] and use of other antihypertensive medications [0.72 (0.54–0.95)]. The inverse association was most pronounced among patients with locally advanced/metastatic disease: [0.35 (0.18–0.68)]. A lower-magnitude inverse association was observed for selective β-blocker use [0.91 (0.83–0.99)]. Largely similar inverse associations were observed for hydrophilic [0.82 (0.70–0.95)] and lipophilic [0.91 (0.83–1.00)] β-blocker use. β-blocker use, particularly of the nonselective type, was associated with lower BCSM, especially in patients with locally advanced/metastatic urothelial bladder cancer. [ABSTRACT FROM AUTHOR]

Recent trials on novel heart failure (HF) treatments (angiotensin receptor-neprilysin inhibitor, sodium-glucose cotransporter 2 inhibitor, and ivabradine) emphasize the use of conventional medical therapy (angiotensin-converting enzyme inhibitors, beta-blockers [BB], and mineral corticosteroid receptor antagonists). We aimed to evaluate the prescription rate of conventional medical therapy and its association with long-term outcomes in patients eligible for recent trials. We examined 1295 consecutive patients with HF with reduced ejection fraction (HFrEF) from a multicenter registry (WET-HF registry). We assessed conventional medical therapy implementation among patients meeting the PARADIGM-HF/DAPA-HF and SHIFT enrollment criteria. We also examined the association between conventional medical therapy use and long-term outcomes within each enrollment criterion. Overall, 62.2% and 35.3% of HFrEF patients met the enrollment criteria of the PARADIGM-HF/DAPA-HF and SHIFT trials. Only 33.9% and 31.9% received full conventional medical therapy within each patient subset. Notably, 84.2% of patients who met the SHIFT enrollment criteria were on BB, and only 23.0% and 4.4% were on ≥50% or the full recommended dose, respectively. Implementation of full conventional medical therapy use was associated with lower 2-year mortality and HF readmission rates in the PARADIGM-HF/ DAPA-HF eligible group (HR 0.68, 95% CI 0.50–0.92). The use of BB at ≥50% of the recommended dose was associated with lower 2-year mortality and HF readmission rates in the SHIFT-eligible group (HR 0.50, 95% CI 0.30–0.84). Conventional medical therapy was underutilized among patients eligible for novel trials within a Japanese HF registry. Further efforts to optimize conventional medical therapy are needed. • Recent novel heart failure (HF) trials recommended the use of conventional medical therapy in the enrollment criteria. • 62.2% and 35.3% of the patients met the enrollment criteria of the PARADIGM-HF/DAPA-HF and the SHIFT trials. • conventional medical therapy was underutilized (~30%) among patients eligible for novel HF trials. • Use of conventional medical therapy was associated with lower rates of 2-year mortality and HF readmission. • Optimizing conventional medical therapy remains a crucial step in improving the outcomes of HF patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to conduct a systematic review and meta-analysis to investigate the impact of premorbid beta-blockers on mortality in patients with sepsis. Data Sources: We searched EMBASE, the Cochrane Central Register of Controlled Trials, and MEDLINE for eligible studies. The protocol was registered at the PROSPERO (CRD42021256813). Study Selection: Two authors independently evaluated the following inclusion criteria: (1) randomized controlled trials, cohort studies, cross-sectional studies; (2) patients with sepsis aged ≥18 years, and (3) premorbid beta-blocker use. Data Extraction: Two authors extracted the patients' characteristics and outcomes independently. All analyses were performed using the random-effects models. The primary outcome was short-term mortality, defined as mortality within 30 days, in-hospital or intensive care unit mortality. Data Synthesis: Ten studies (n = 24 748 patients) were included. The pooled odds ratio (OR) of short-term mortality associated with the premorbid use of beta-blockers was 0.85 (95% confidence interval [CI], 0.69-1.04; P = .12; I² = 50%). Five studies reported an adjusted OR of short-term mortality. The pooled adjusted OR of short-term mortality associated with the premorbid use of beta-blockers was 0.73 (95% CI, 0.65-0.83; P < .001; I² = 0%). Conclusion: Premorbid beta-blockers were associated with a lower short-term mortality in patients with sepsis. [ABSTRACT FROM AUTHOR]

Introduction: Beta‐blockers are prescribed for many pregnant women with heart disease, but whether there is a dose‐dependent effect on fetal growth remains to be examined. We aimed to investigate if antenatal beta‐blocker use and dose were associated with delivering a small‐for‐gestational‐age infant among women with heart disease. Material and methods: Our cohort included women with heart disease who delivered at Oslo University Hospital between 2006 and 2015. Maternal heart disease was classified into modified WHO risk scores. Women with beta‐blocker treatment were dichotomized into whether they had been treated with a low or high dose based on clinical factors. We compared the risk of delivering a small‐for‐gestational‐age infant in women exposed to high doses, low doses, or with no exposure to antenatal beta‐blockers while adjusting for severity of maternal heart disease in logistic regression models. Results: Of a total of 540 pregnancies among women with heart disease, 163 (30.2%) were exposed to beta‐blocker treatment. The majority were treated with metoprolol (86.5%). Almost twice as many babies in the beta‐blocker group were small‐for‐gestational‐age, compared with the non‐exposed group (19.8 vs 9.5%, P < 0.001). Women using a high‐dose beta‐blocker had a five‐fold increased risk of delivering a small‐for‐gestational‐age infant compared with non‐exposure (adjusted odds ratio [aOR] 4.89, 95% confidence interval [CI] 2.22–10.78, P < 0.001). Women using a low dose of beta‐blocker had a two‐fold increased risk of delivering a small‐for‐gestational‐age infant; however, the confidence interval included the null (aOR 1.75, 95% CI 0.83–3.72, P = 0.143). Results when restricting the analyses to metoprolol showed the same pattern, but with attenuation of risks. Conclusions: We found a five‐fold increased risk of delivering a small‐for‐gestational‐age infant in women with heart disease treated with a high dose of beta‐blocker, and a two‐fold increased risk among those treated with a low dose, showing an apparent dose–response relation. Close monitoring of fetal growth is warranted among women with heart disease treated with beta‐blockers. As drug therapy in pregnancy concerns both mother and fetus, an optimum balance for both should be the goal. [ABSTRACT FROM AUTHOR]

Purpose of Review: The aim of this review is to aid in decision-making when choosing safe and effective options for preventive migraine medications. Recent Findings: In Part 2, we have compiled clinically relevant safety considerations for commonly used migraine prophylactic treatments. Preventive treatment of episodic migraine includes nonspecific and migraine-specific drugs. While medications from several pharmacological classes–such as anticonvulsants, beta-blockers, and antidepressants–have an established efficacy in migraine prevention, they are associated with a number of side effects. The safety of migraine-specific treatments such as anti-CGRP monoclonal antibodies and gepants are also discussed. Summary: This review highlights safety concerns of commonly used migraine prophylactic agents and offers suggestions on how to mitigate those risks. [ABSTRACT FROM AUTHOR]

الملخص: أهداف البحث: ينبغي البدء باستعمال مانع بيتا مع المرضى الذين يعانون من فشل القلب الحاد المستقر. وينبغي إجراء معايرة بعد فترة أسبوعين من استعمال مانع بيتا. ولا تزال فوائد معايرة مانع بيتا الدقيقة غير واضحة. تهدف هذه الدراسة إلى التحقيق في نتائج المعايرة لمانع بيتا الدقيقة لدى مرضى فشل القلب الحاد المستقر مع انخفاض كسر طرد البطين الأيسر. طرق البحث: في هذه الدراسة الأترابية الاستعادية، قمنا بتحليل البيانات السريرية من سجل قصور القلب. تم تقسيم مرضى فشل القلب الحاد الذين يعانون من انخفاض كسر طرد البطين الأيسر>٤٠٪ إلى مجموعتين، مجموعة معايرة مانع بيتا الدقيقة ومجموعة موجهة حسب المبادئ التوجيهية. تم تعريف النتائج الأولية على أنها مجموعة من ارتفاع تفاقم قصور القلب، وعدم انتظام ضربات القلب البطينية، والوفيات أثناء دخول المستشفى. وقد اعتبرنا النتائج الثانوية مكونات للنتائج الأولية وكذلك النتائج خلال المتابعة التي تستغرق ٩٠ يوما بعد الخروج من المستشفى، بما في ذلك إعادة التنويم بقصور القلب والوفيات. النتائج: لم تكن النتائج الأولية بين المجموعتين مختلفة بشكل كبير (١٢.٣٪ مقابل ٢٤.٤٪؛ المخاطر النسبية ٠.٥١). ومع ذلك، فإن معايرة مانع بيتا الدقيقة خفضت عدم انتظام ضربات القلب البطينية (٥.٧٪ مقابل ١٧.٨٪؛ ٠.٣٢). ومعدل إعادة التنويم بقصور القلب (٢.٦٪ مقابل ٧.٥٪؛ ٠.٣٥) ومعدل الوفيات (٤.٣٪ مقابل ٥٪؛ ٠.٨٧)، ولم يتم العثور على اختلاف بشكل ملحوظ في الوفيات بين المجموعتين. الاستنتاجات: بالمقارنة مع معايرة مانع بيتا حسب توجيهات المبادئ التوجيهية، كانت معايرة مانع بيتا الدقيقة أكثر أمانا في مرضى فشل القلب الحاد المستقر وانخفاض كسر طرد البطين الأيسر الذين تم تثبيت حالتهم سابقا. بالإضافة إلى ذلك، فإن معايرة مانع بيتا الدقيقة قللت بشكل فاعل من أحداث عدم انتظام ضربات القلب البطينية. Abstract: Objectives: A beta-blocker should be initiated in patients with stable acute heart failure (AHF). Beta-blocker titration should be conducted after a two-week interval. The benefits of aggressive beta-blocker titration are still unclear. This study aimed to investigate the aggressive beta-blocker titration outcomes in stabilized AHF patients with low left ventricular ejection fraction (LVEF). Methods: In this retrospective cohort study, we analysed clinical data from the heart failure (HF) registry. AHF Patients with LVEF

Abstract Background Cardiogenic shock (CS) is associated with significant morbidity and mortality. The impact of beta-blocker (BB) use on patients who develop CS remains unknown. We sought to evaluate the clinical outcomes and hemodynamic response profiles in patients treated with BB in the 24 h prior to the development of CS. Methods Patients with CS enrolled in the DObutamine compaREd to MIlrinone trial were analyzed. The primary outcome was a composite of all-cause mortality, resuscitated cardiac arrest, need for cardiac transplant or mechanical circulatory support, non-fatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy. Secondary outcomes included the individual components of the primary composite and hemodynamic response profiles derived from pulmonary artery catheters. Results Among 192 participants, 93 patients (48%) had received BB therapy. The primary outcome occurred in 47 patients (51%) in the BB group and in 52 (53%) in the no BB group (RR 0.96; 95% CI 0.73–1.27; P = 0.78) throughout the in-hospital period. There were fewer early deaths in the BB group (RR 0.41; 95% CI 0.18–0.95; P = 0.03). There were no differences in other individual components of the primary outcome or in hemodynamic response between the two groups throughout the remainder of the hospitalization. Conclusions BB therapy in the 24 h preceding the development of CS did not negatively influence clinical outcomes or hemodynamic parameters. On the contrary, BB use was associated with fewer deaths in the early resuscitation period, suggesting a paradoxically protective effect in patients with CS. Trial registration ClinicalTrials.gov Identifier: NCT03207165

Background/Aims Beta-blockers (BBs) have been shown to improve clinical outcomes in heart failure (HF) patients. We evaluated the prescribing status of BBs in patients with HF with reduced ejection fraction (HFrEF) at discharge according to the presence or not of bradycardia, and its effect on prognosis. Methods Study data were obtained from a multicenter cohort of 3,200 patients hospitalized for HF. Patients were classified into four groups according to the presence of bradycardia and use of BBs at discharge. The primary outcome was the incidence of all-cause death during follow-up. Results Of 1,584 patients with HFrEF, 281 patients died during follow-up (median 523 days, mean 578.5 ± 429.7 days). In patients with bradycardia, the all-cause death rate did not significantly differ according to the use of BBs, but in those patients without bradycardia, the incidence of all-cause death was significantly lower in the BBs group than the no BBs group. Among these four groups, patients with heart rate (HR) ≥ 60 beats/min with no BBs group had the lowest cumulative death-free survival rate. In addition, HR ≥ 60 beats/min with BBs use was independently associated with a 31% reduced risk of all-cause death in patients with HFrEF. Conclusions BBs had a beneficial effect on clinical prognosis only in those HFrEF patients without bradycardia. Therefore, BBs should be given by clinicians to HF patients without bradycardia to improve their clinical outcomes.

BackgroundBeta-blockers are commonly prescribed for patients with cardiovascular disease. Providers have been wary of treating chronic obstructive pulmonary disease (COPD) patients with beta-blockers due to concern for bronchospasm, but retrospective studies have shown that cardio-selective beta-blockers are safe in COPD and possibly beneficial. However, these benefits may reflect symptom improvements due to the cardiac effects of the medication. The purpose of this study is to evaluate associations between beta-blocker use and both exacerbation rates and longitudinal measures of lung function in two well-characterized COPD cohorts.MethodsWe retrospectively analyzed 1219 participants with over 180 days of follow up from the STATCOPE trial, which excluded most cardiac comorbidities, and from the placebo arm of the MACRO trial. Primary endpoints were exacerbation rates per person-year and change in spirometry over time in association with beta blocker use.ResultsOverall 13.9% (170/1219) of participants reported taking beta-blockers at enrollment. We found no statistically significant differences in exacerbation rates with respect to beta-blocker use regardless of the prevalence of cardiac comorbidities. In the MACRO cohort, patients taking beta-blockers had an exacerbation rate of 1.72/person-year versus a rate of 1.71/person-year in patients not taking beta-blockers. In the STATCOPE cohort, patients taking beta-blockers had an exacerbation rate of 1.14/person-year. Patients without beta-blockers had an exacerbation rate of 1.34/person-year. We found no detrimental effect of beta blockers with respect to change in lung function over time.ConclusionWe found no evidence that beta-blocker use was unsafe or associated with worse pulmonary outcomes in study participants with moderate to severe COPD.

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BackgroundAlthough high resting heart rate (RHR) is known to be associated with an increased risk of mortality and hospital admission in patients with heart failure, the relationship between RHR and ischemic stroke remains unclear. This study is aimed at investigating the relationship between RHR and ischemic stroke in patients with heart failure in sinus rhythm.MethodsWe examined 2,060 patients with systolic heart failure in sinus rhythm from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. RHR was determined from baseline electrocardiogram, and was examined as both a continuous variable and a categorical variable using quartiles. Ischemic strokes were identified during follow-up and adjudicated by physician review.ResultsDuring 3.5 ± 1.8 years of follow-up, 77 patients (5.3% from Kaplan-Meier [KM] curve) experienced an ischemic stroke. The highest incidence of ischemic stroke (21/503 [KM 6.9%]) was observed in the lowest RHR quartile (RHR 79 beats/min (p = 0.693). Multivariable Cox proportional hazards analysis revealed that RHR was significantly associated with ischemic stroke (hazard ratio per unit decrease: 1.07, 95% CI 1.02-1.13, when RHR