Search

Background: Limited data exists to evaluate the optimal management of outpatient beta blocker therapy when patients with heart failure with reduced ejection fraction (HFrEF) are admitted for acute decompensated heart failure (ADHF). Objective: This study aimed to compare the effects of holding or decreasing the dose of outpatient beta blocker therapy vs continuation of therapy on rates of tachyarrhythmias during admission for ADHF. Methods: This single-center, retrospective cohort study divided patients with HFrEF (left ventricular ejection fraction less than or equal to 40%) admitted for ADHF into two cohorts: one that had their outpatient beta blocker continued at the same dose upon admission and one that had it held or dose decreased. The primary outcome was a composite of non-sustained or sustained ventricular tachycardia, ventricular fibrillation, or atrial fibrillation or flutter with rapid ventricular response during the hospitalization. Secondary outcomes included the individual tachyarrhythmias in the primary outcome, in-hospital mortality, and 90-day re-admission for heart failure. Results: Of the 137 patients included, 82 were in the continuation cohort and 55 in the discontinuation/reduction cohort. The median length of stay was 5.3 days (interquartile range, 3.8-7.6). No significant difference in the primary composite outcome was found between the discontinuation/reduction and continuation cohorts (29.1% vs 22.0%; relative risk [95% confidence interval], 1.33 [.74-2.37]; P =.420). No significant differences were seen between the two cohorts for any of the secondary outcomes. Conclusion: Beta blocker therapy adjustment on admission for ADHF may not affect the occurrence of tachyarrhythmias in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Introduction: Supraventricular tachycardia (SVT) is a common pediatric arrhythmia. Beta blockers (BBs) and calcium channel blockers (CCBs) are used for treatment despite little data examining their use. We describe the prescriptive tendencies, efficacy, and tolerability of BBs and CCBs used in the treatment of pediatric SVT. Methods and Results: This is a multicenter retrospective cohort study from three academic children's hospitals. Individuals aged 1–21 years at time of SVT diagnosis initiated on a BB or a CCB between 01/01/2010 and 12/31/2020 were included. Exclusion criteria were pre‐excitation, ectopic atrial tachycardia, and hemodynamically significant heart disease. Demographic, comorbidity, symptomatology, and medication data were collected. Treatment success was defined using a composite data abstraction tool. Of 164 patients, 151 received a BB and 13 received a CCB. The success rate on the initial dosage was 46% for both BB and CCB; the success rate following dosage adjustments was also comparable for BBs (98/151, 65%) and CCBs (9/13, 69%). While 27 (18%) BB patients experienced intolerable side effects, no CCB patient did. Conclusion: Treatment with a BB or CCB was successful in half of patients. BBs were prescribed more frequently than CCBs but were associated with more side effects. [ABSTRACT FROM AUTHOR]

Chronic heart failure (CHF) is a rare entity in children but carries a burden of high mortality and morbidity. Medical treatment of pediatric CHF is largely based on guidelines for the adult population. In contrast to adults, evidence for the efficacy of medications in treating CHF in children is sparse. This may be due to the difficulty of conducting high-powered studies in children or to true differences in the mechanisms of CHF pathophysiology. Recent observations suggest that CHF in children differs from adults at the molecular and cellular levels. Different pathways are involved, leading to less fibrosis and hypertrophy than in adults, with potential implications for therapy. The main pathophysiological goals of medical treatment of pediatric CHF due to systemic left ventricular dysfunction are discussed in this review. These include preload and afterload optimization, diminishing cardiomyocyte apoptosis and necrosis as well as interstitial fibrosis, and optimizing myocardial oxygen consumption. The pediatric myocardium should be provided with optimal conditions to achieve its regenerative potential. The cornerstones of medical CHF therapy are angiotensin converting enzyme inhibitors (ACEI), beta blockers and mineralocorticoid receptor antagonists. There are potential benefits of tissue ACEI and β1-selective beta blockers in children. Angiotensin receptor blockers are an alternative to ACEI and their slightly different mechanism of action may confer certain advantages and disadvantages. Diuretics are employed to achieve a euvolemic state. Digoxin is used more frequently in children than in adults. Promising new drugs already routinely used in adults include angiotensin receptor-neprilysin inhibitors and sodium-glucose contransporter 2 inhibitors. [ABSTRACT FROM AUTHOR]

OBJECTIVES Previous reports suggest that betablockers appear non-beneficial after surgical aortic valve replacement (SAVR). This study aims to clarify the associations between betablockers and long-term outcome after SAVR. METHODS All patients with isolated SAVR due to aortic stenosis in Sweden between 2006 and 2020, alive at 6 months after surgery, were included. Patients were identified in the SWEDEHEART registry, and records were merged with data from 3 other mandatory national registries. Association between dispensed betablockers and major adverse cardiovascular events (MACE) (all-cause mortality, myocardial infarction and stroke) was analyzed using Cox proportional hazards models, with time-updated data on medication and adjusted for age, sex and comorbidities at baseline. RESULTS In total, 11 849 patients were included [median follow-up 5.4 years (range 0–13.5)]. Betablockers were prescribed to 79.7% of patients at baseline, decreasing to 62.2% after 5 years. Continuing treatment was associated with higher risk of MACE [adjusted hazard ratio 1.14 (95% confidence interval, CI 1.05–1.23)]. The association was consistent over subgroups based on age, sex and comorbidities except atrial fibrillation [hazard ratio (HR) 1.05 (95% CI 0.93–1.19)]. A sensitivity analysis including time-updated data on comorbidites attenuated the difference between the groups [HR 1.04 (95% CI 0.95–1.14, P  = 0.33)]. CONCLUSIONS Treatment with betablockers did not appear to be associated with inferior long-term outcome after SAVR, when adjusting for new concomitant diseases. Thus, it is likely that it is the underlying cardiac diseases that are associated with MACE rather than betablocker treatment. [ABSTRACT FROM AUTHOR]

Abstract Background The beta-blocker (BB) initiation in acute heart failure (AHF) patients is still controversial. Some show the benefit of BB employment in decreasing the mortality outcome. This study aims to assess the safety and efficacy of in-hospital and long-term outcomes of BB initiation in AHF hospitalized patients. We searched multiple databases examining the outcome of AHF patients who had administered BB as the therapy initiation. Primary outcomes were all-cause mortality, composite endpoint after BB initiation when hospitalized, and post-discharge all-cause mortality. The secondary outcomes were adverse events after in-hospital BB initiation, including hypotension and symptomatic bradycardia after BB initiation when hospitalization and rehospitalization. Results Eight cohort studies with 16,639 patients suffering from AHF and cardiogenic shock, with 9923 participants allocated to the early BB group and 6,713 patients in the control group. The follow-up durations ranged from 2 to 24 months. Early BB administration significantly reduced in-hospital composite endpoints (RR: 0.42; 95% CI (0.30–0.58); p

Abstract Background Glaucoma treatment often involves multi-drug regimens, which can lead to poor adherence and side effects. Fixed-dose combinations aim to improve adherence and reduce side effects compared to traditional therapies. This study aimed to compare the prevalence and clinical characteristics of ocular allergy in glaucoma patients using brinzolamide 1.0%/brimonidine 0.2% fixed combination (BBFC), with and without concurrent β-blocker. Methods Of these, 176 patients used a β-blocker concurrently, whereas 96 patients did not. Allergy prevalence, allergy type, and allergy occurrence time were compared between the concurrent and non-concurrent β-blocker-usage groups. Ocular allergies were classified and evaluated using Kaplan–Meier survival analysis. Results Allergy prevalence was 10.23% and 15.63% (p = 0.193), whereas allergy occurrence time was 15.92 ± 13.80 months and 6.26 ± 6.20 months (p = 0.04) in the concurrent and non-concurrent β-blocker-usage groups, respectively. Kaplan–Meier survival analysis indicated that half of the allergies in the concurrent β-blocker-usage group occurred within 12.5 months, with the BBFC discontinuation rate gradually increasing up to 36 months. Contrarily, half of the allergies in the non-concurrent β-blocker-usage group occurred within 3.3 months, with a rapid increase in BBFC discontinuation rate the first 6 months. Intergroup differences in allergy types were significant (p = 0.015). Among all patients with allergy, the average allergy occurrence time of blepharoconjunctivitis, papillary conjunctivitis, and follicular conjunctivitis was 12.52, 9.53, and 13.23 months, respectively. Follicular conjunctivitis tended to occur later than papillary conjunctivitis (p = 0.042). In the concurrent β-blocker-usage group, follicular conjunctivitis was the most prevalent allergy type (61.1%), whereas papillary conjunctivitis was the most common (66.7%) in in the non-concurrent β-blocker-usage group. Conclusions Concurrent use of β-blocker with BBFC decreases allergy prevalence, delays allergy onset, and predominantly results in follicular conjunctivitis, thereby facilitating longer treatment duration. Understanding these characteristics of allergy in BBFC users is useful to manage patients and improve treatment adherence. This study provides insights into the role of β-blockers in modulating ocular allergy in BBFC-treated glaucoma patients, highlighting implications for clinical practice and patient education.

Background: The beta-blocker (BB) initiation in acute heart failure (AHF) patients is still controversial. Some show the benefit of BB employment in decreasing the mortality outcome. This study aims to assess the safety and efficacy of in-hospital and long-term outcomes of BB initiation in AHF hospitalized patients. We searched multiple databases examining the outcome of AHF patients who had administered BB as the therapy initiation. Primary outcomes were all-cause mortality, composite endpoint after BB initiation when hospitalized, and post-discharge all-cause mortality. The secondary outcomes were adverse events after in-hospital BB initiation, including hypotension and symptomatic bradycardia after BB initiation when hospitalization and rehospitalization. Results: Eight cohort studies with 16,639 patients suffering from AHF and cardiogenic shock, with 9923 participants allocated to the early BB group and 6,713 patients in the control group. The follow-up durations ranged from 2 to 24 months. Early BB administration significantly reduced in-hospital composite endpoints (RR: 0.42; 95% CI (0.30–0.58); p < 0.001), in-hospital all-cause mortality (RR: 0.43; 95% CI (0.31–0.61); p < 0.001), discharge mortality (RR: 0.51; 95% CI (0.41–0.63); p < 0.001), and rehospitalization (RR: 0.57; 95% CI (0.44–0.74); p < 0.001). There were no discernible differences in in-hospital BB-related adverse events between the two groups (p = 0.13). Subgroup analyses conducted on AHF patients presenting with cardiogenic shock revealed no significant differences in in-hospital composite endpoint and in-hospital mortality, and similar results were shown in the naive BB population. Conclusions: The BB initiation in AHF patients shows advantages in efficacy and safety outcome. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast cancer (BCa) is a pathology that affects the world population. Patients present risk factors for osteopenia and osteoporosis, such as chronic stress, estrogen deprivation due to hormonal treatment, a menopausal status, and decreased physical activity. An available alternative is the use of nonselective beta blockers (nsBBs) that have antitumoral properties, and in other diseases, antiresorptive and osteoforming effects. We demonstrated that BCa patients taking nsBBs had a greater bone mineral density and a lower incidence of osteoporosis and osteopenia than untreated patients. Although our study has several limitations, such as its retrospective design and single-center population, it revealed promising effects of nsBBs on the prevention and treatment of osteoporosis and osteopenia in patients with BCa. Breast cancer (BCa) is related to chronic stress and can reduce the bone mineral density (BMD) through neurochemicals related to beta-adrenergic receptor (ADRB) 1 and 2. Selective beta blockers (sBBs) and nonselective beta blockers (nsBBs) are used to treat systemic arterial hypertension (SAH) and may have osteoprotective effects, as they inhibit ADRBs. To evaluate the effects of sBBs and nsBBs on the BMD of Mexican patients with BCa. A retrospective study was conducted. We included 191 Mexican women with BCa without SAH and with SAH treated with nsBBs, sBBs, and diuretics. BMD was evaluated using a bone density scan (DEX scan). A greater average BMD (p < 0.05) was observed in patients with prior treatment with both nsBBs and sBBs (0.54 ± 0.94 and −0.44 ± 1.22, respectively) compared to patients treated with diuretics or without SAH (−1.73 ± 0.83 and −1.22 ± 0.98, respectively). Regarding the diagnosis of osteoporosis/osteopenia, no cases were observed in patients treated with nsBBs, whereas 5.6% of the patients treated with sBBs presented osteopenia. A total of 23.1% and 10.6% patients managed with diuretics or without treatment presented with osteoporosis and 61.5% and 48% patients managed with loop diuretics and without treatment presented with osteopenia, respectively (p < 0.05). Treatment with nsBBs is a promising option for the prevention and management of osteoporosis/osteopenia in Mexican patients with BCa; however, further prospective studies are needed. [ABSTRACT FROM AUTHOR]

Background: Glaucoma treatment often involves multi-drug regimens, which can lead to poor adherence and side effects. Fixed-dose combinations aim to improve adherence and reduce side effects compared to traditional therapies. This study aimed to compare the prevalence and clinical characteristics of ocular allergy in glaucoma patients using brinzolamide 1.0%/brimonidine 0.2% fixed combination (BBFC), with and without concurrent β-blocker. Methods: Of these, 176 patients used a β-blocker concurrently, whereas 96 patients did not. Allergy prevalence, allergy type, and allergy occurrence time were compared between the concurrent and non-concurrent β-blocker-usage groups. Ocular allergies were classified and evaluated using Kaplan–Meier survival analysis. Results: Allergy prevalence was 10.23% and 15.63% (p = 0.193), whereas allergy occurrence time was 15.92 ± 13.80 months and 6.26 ± 6.20 months (p = 0.04) in the concurrent and non-concurrent β-blocker-usage groups, respectively. Kaplan–Meier survival analysis indicated that half of the allergies in the concurrent β-blocker-usage group occurred within 12.5 months, with the BBFC discontinuation rate gradually increasing up to 36 months. Contrarily, half of the allergies in the non-concurrent β-blocker-usage group occurred within 3.3 months, with a rapid increase in BBFC discontinuation rate the first 6 months. Intergroup differences in allergy types were significant (p = 0.015). Among all patients with allergy, the average allergy occurrence time of blepharoconjunctivitis, papillary conjunctivitis, and follicular conjunctivitis was 12.52, 9.53, and 13.23 months, respectively. Follicular conjunctivitis tended to occur later than papillary conjunctivitis (p = 0.042). In the concurrent β-blocker-usage group, follicular conjunctivitis was the most prevalent allergy type (61.1%), whereas papillary conjunctivitis was the most common (66.7%) in in the non-concurrent β-blocker-usage group. Conclusions: Concurrent use of β-blocker with BBFC decreases allergy prevalence, delays allergy onset, and predominantly results in follicular conjunctivitis, thereby facilitating longer treatment duration. Understanding these characteristics of allergy in BBFC users is useful to manage patients and improve treatment adherence. This study provides insights into the role of β-blockers in modulating ocular allergy in BBFC-treated glaucoma patients, highlighting implications for clinical practice and patient education. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We aimed to 1) describe patterns of beta-blocker utilization among critically ill patients following moderate-severe traumatic brain injury (TBI) and 2) examine the association of early beta-blocker exposure with functional and clinical outcomes following injury. DESIGN: Retrospective cohort study. SETTING: ICUs at 18 level I, U.S. trauma centers in the Transforming Clinical Research and Knowledge in TBI (TRACK-TBI) study. PATIENTS: Greater than or equal to 17 years enrolled in the TRACK-TBI study with moderate-severe TBI (Glasgow Coma Scale of

The text discusses the importance, incidence, causes, and risk factors of acute intraocular pressure (IOP) elevation after cataract surgery, particularly in high-risk patients with preexisting optic nerve damage. It highlights the biphasic nature of IOP elevations post-surgery and the potential complications, such as post-cataract surgery optic neuropathy. The document also provides recommendations for prophylaxis and treatment, including the use of topical and systemic medications, as well as surgical interventions like microinvasive glaucoma surgeries (MIGS) for patients with sustained IOP elevation. Surgeons are advised to consider individual patient factors and history when making decisions regarding prophylaxis and treatment. [Extracted from the article]

Introduction: Ivabradine reduces heart rate (HR), episodes of angina, and nitrate consumption, and increases exercise capacity in patients with chronic angina (CA). In this exploratory study, myocardial perfusion scintigraphy (MPS) was used to evaluate changes in the percentage of myocardial ischemia after ivabradine therapy in patients with CA. Methods: This prospective, open-label, single-arm study included patients with CA receiving maximum tolerated doses of beta blockers, who had a resting HR ≥ 70 bpm and had experienced ischemia according to MPS during an exercise test at baseline. Participants received ivabradine 5 mg twice daily (titrated according to HR) concomitant with beta blockers. A second MPS was performed after 3 months, without interruption of treatment with beta blockers or ivabradine. The primary outcome was change in the percentage of myocardial ischemia from baseline to 3 months. Time to ischemia during the exercise test, the proportion of patients presenting angina during the exercise test, and health status, assessed using the seven-item Seattle Angina Questionnaire-7 (SAQ-7), were also evaluated. Results: Twenty patients (3 females) with a mean (± standard deviation [SD]) age of 62.2 ± 6.5 years were included in the study, of whom 55% had diabetes, 70% had previous myocardial revascularization, and 45% had previous myocardial infarction. The percentage of patients with myocardial ischemia significantly decreased from baseline to 3 months after initiation of treatment with ivabradine (− 2.9%; 95% confidence interval [CI] − 0.3 to − 5.5; p = 0.031). Mean time to appearance of ischemia increased from 403 ± 176 s at baseline to 466 ± 136 s at 3 months after initiation of ivabradine (Δ62 s; 95% CI 18–106 s; p = 0.008), and the proportion of patients experiencing angina during the exercise test decreased from 40% at baseline to 5% also at 3 months (p = 0.016). Mean resting HR decreased from 76 ± 7 bpm at baseline to 55 ± 8 bpm at 3 months (p < 0.001). The mean SAQ-7 summary score improved from 69 ± 21 at baseline to 83 ± 12 at 3 months (p = 0.001). No serious adverse effects were reported. Conclusion: Ivabradine added to beta blockers was associated with a reduction in detectable myocardial ischemia by MPS in patients with CA. Infographic available for this article. Trial Registration: The trial has been retrospectively registered with the Brazilian Registry of Clinical Trials (REBEC) under the following number RBR-5fysqrh (date of registration: 30 November 2023). [ABSTRACT FROM AUTHOR]

Abstract Introduction Ivabradine reduces heart rate (HR), episodes of angina, and nitrate consumption, and increases exercise capacity in patients with chronic angina (CA). In this exploratory study, myocardial perfusion scintigraphy (MPS) was used to evaluate changes in the percentage of myocardial ischemia after ivabradine therapy in patients with CA. Methods This prospective, open-label, single-arm study included patients with CA receiving maximum tolerated doses of beta blockers, who had a resting HR ≥ 70 bpm and had experienced ischemia according to MPS during an exercise test at baseline. Participants received ivabradine 5 mg twice daily (titrated according to HR) concomitant with beta blockers. A second MPS was performed after 3 months, without interruption of treatment with beta blockers or ivabradine. The primary outcome was change in the percentage of myocardial ischemia from baseline to 3 months. Time to ischemia during the exercise test, the proportion of patients presenting angina during the exercise test, and health status, assessed using the seven-item Seattle Angina Questionnaire-7 (SAQ-7), were also evaluated. Results Twenty patients (3 females) with a mean (± standard deviation [SD]) age of 62.2 ± 6.5 years were included in the study, of whom 55% had diabetes, 70% had previous myocardial revascularization, and 45% had previous myocardial infarction. The percentage of patients with myocardial ischemia significantly decreased from baseline to 3 months after initiation of treatment with ivabradine (− 2.9%; 95% confidence interval [CI] − 0.3 to − 5.5; p = 0.031). Mean time to appearance of ischemia increased from 403 ± 176 s at baseline to 466 ± 136 s at 3 months after initiation of ivabradine (Δ62 s; 95% CI 18–106 s; p = 0.008), and the proportion of patients experiencing angina during the exercise test decreased from 40% at baseline to 5% also at 3 months (p = 0.016). Mean resting HR decreased from 76 ± 7 bpm at baseline to 55 ± 8 bpm at 3 months (p

Heart failure and chronic kidney disease (CKD) share several mediators of cardiac pathological remodelling. Akin to heart failure, this remodelling sets in motion a vicious cycle of progressive pathological hypertrophy and myocardial dysfunction in CKD. Several decades of heart failure research have shown that beta blockade is a powerful tool in preventing cardiac remodelling and breaking this vicious cycle. This phenomenon remains hitherto untested in CKD. Therefore, we set out to test the hypothesis that beta blockade prevents cardiac pathological remodelling in experimental uremia. Wistar rats had subtotal nephrectomy or sham surgery and were followed up for 10 weeks. The animals were randomly allocated to the beta blocker metoprolol (10 mg/kg/day) or vehicle. In vivo and in vitro cardiac assessments were performed. Cardiac tissue was extracted, and protein expression was quantified using immunoblotting. Histological analyses were performed to quantify myocardial fibrosis. Beta blockade attenuated cardiac pathological remodelling in nephrectomised animals. The echocardiographic left ventricular mass and the heart weight to tibial length ratio were significantly lower in nephrectomised animals treated with metoprolol. Furthermore, beta blockade attenuated myocardial fibrosis associated with subtotal nephrectomy. In addition, the Ca++- calmodulin-dependent kinase II (CAMKII) pathway was shown to be activated in uremia and attenuated by beta blockade, offering a potential mechanism of action. In conclusion, beta blockade attenuated hypertrophic signalling pathways and ameliorated cardiac pathological remodelling in experimental uremia. The study provides a strong scientific rationale for repurposing beta blockers, a tried and tested treatment in heart failure, for the benefit of patients with CKD. [ABSTRACT FROM AUTHOR]

BackgroundPatients with hypertension are at a high risk of atrial fibrillation (AF). Recent research has indicated the varying effects of antihypertensive medications on developing AF.ObjectivesWe investigated the relationship between different types of antihypertensive medications and the risk of AF occurrence.MethodsWe analyzed data from 113,582 subjects with national health screening examinations between 2009 and 2014. The study population was categorized according to antihypertensive medication type. The primary outcome was the incidence of AF.ResultsAmong 113,582 subjects (mean age 59.4 ± 12.0 years, 46.7% men), 93,557 received monotherapy [angiotensin receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACEi), beta-blockers, calcium channel blockers (CCB), or diuretics], while 34,590 received combination therapy (ARB/beta-blockers, ARB/CCB, ARB/diuretics, or ARB/CCB/diuretics). During a mean follow-up duration of 7.6 ± 2.1 years, 3.9% of patients were newly diagnosed with AF. In monotherapy, ACEi and CCB had similar AF risks as ARB, while beta-blockers and diuretics showed higher AF risks than ARB. In combination therapy, ARBs/CCBs and ARBs/diuretics had the lowest AF risk, whereas ARBs/beta-blockers had the highest compared to ARB/CCB. Among the specific ARBs, the AF risk varied insignificantly, except for telmisartan and candesartan.ConclusionsIn hypertensive patients receiving monotherapy, ACEi and CCB showed a similar AF risk as ARBs, while beta-blockers and diuretics were associated with a higher risk. Among those receiving combination therapy, ARBs/CCBs and ARBs/diuretics had the lowest AF risk, whereas ARBs/beta-blockers showed the highest risk. Various types of ARBs have different associations with AF risk.

Purpose: Hemangiomas are the most common vascular tumors in childhood, and the treatment options have undergone profound changes in recent years. In this study, we aimed to compare the efficacy and safety of beta-blockers on hemangiomas, both topi-cal and oral, with non-pharmacological treatment in the pediatric age group. Material and Methods: We retrospectively reviewed the medical records of pediatric patients with hemangiomas. Results: Fifty-three patients (F/M=40/13) were enrolled in this study. Superficial hemangiomas were detected in 14 (26.4%) patients, and deep hemangiomas were detected in 39 (73.6%) patients. Seventeen patients were followed without medication, 19 were treated with a topical beta blocker, and 17 were treated with an oral beta blocker. Twelve patients with superficial hemangi-omas were followed without medication, while two received topical timolol treatment. A comparison of lesion progression in patients with superficial hemangiomas in the non-pharmacological treatment and topical treatment groups showed that the mean scores of success, in terms of mean fading and reduction in lesion depth, were significantly higher at the first month (7.0 vs. 1.66; p=0.049; 6.0 vs. 1.5; p=0.045). Among patients with deep hemangiomas, a comparison of mean fading scores showed no difference between the oral and topical treatment groups in the first and fourth months (p=0.551, p=0.551). Conclusion: We believe that oral beta-blockers can be used instead of topical treatment in the future, and they will be preferred more by clinicians and families due to less side effects.

Introduction-Postoperative atrial fibrillation (POAF) is a potentially lethal and morbid complication after heart surgery. The present study was conducted to study the use of metoprolol in pre and post isolated CABG cases to reduce the incidence of atrial fibrillation. Material and methods- 50 cases and controls who had undergone isolated CABG surgery with extracorporeal circulation participated in a randomised research. The administration of metoprolol orally to the patients during the postoperative phase was randomised. The results included the identification of persistent arrhythmia that was symptomatic or needed medical attention. Patients having baseline left ventricular ejection fractions less than 35%, prior episodes of AF, a history of bronchospasm, second- and third-degree atrioventricular blocks, inadequate cardiac output, and heart failure were excluded from the trial. Results- In the metoprolol group, 10% patients experienced arrhythmias, compared to 23% in the control group (P=0.03). The arrhythmia that was seen the most commonly (85%) was AF. Arrhythmias occurred in 52% metoprolol-treated patients and 56% control patients among patients aged 70 or older with the 95% confidence interval for the risk was 0.10. Conclusion- In the postoperative period following CABG surgery, metoprolol is useful in reducing arrhythmia, and this effect was especially noticeable in the group of senior patients. [ABSTRACT FROM AUTHOR]

Aim. Pharmacologic reduction in heart rate with beta-blockers (BB) or ivabradine is associated with improved survival in heart failure (HF) with sinus rhythm. We analyzed the association of different heart rate-reducing drug treatments on outcomes in HF outpatients. Methods. Consecutive patients with HF in sinus rhythm referred to a specialized tertiary service were prospectively enrolled from August 2015 until March 2018. Clinical characteristics were assessed at baseline. We performed Cox regression analyses to examine the effect of the resting heart rate and different heart rate-reducing drug regimens on all-cause mortality and a composite endpoint of "all-cause mortality or heart transplantation" over a mean follow-up of 3.1 years. Results. Of the 278 patients included, 213 (76.6%) were male, the median age was 57.0 years (IQR 49.0–66.1), and 185 (73.7%) had an ejection fraction <40%. Most patients received BB in submaximal [n = 118] or maximum dose [n = 136]. Patients on BB in maximum dose plus ivabradine [n = 24] were younger (53.0 vs. 58.0 years) and had a lower EF (25 vs. 31%). Higher resting heart rate was associated with an increased risk of death or transplantation (HR 1.03 [1.01, 1.06], p = 0.0072), even after adjusting for age and sex. There were no differences between the groups concerning all-cause mortality or the composite endpoint. Conclusion. Our prospective study confirms the association between low heart rate and survival in HF patients receiving various heart rate-reducing medications. We could not identify a specific effect of either regimen. [ABSTRACT FROM AUTHOR]

In patients with heart failure (HF), the neuroendocrine systems of the sympathetic nervous system (SNS), the renin–angiotensin–aldosterone system (RAAS) and the arginine vasopressin (AVP) system, are activated to various degrees producing often-observed tachycardia and concomitant increased systemic vascular resistance. Furthermore, sustained neurohormonal activation plays a key role in the progression of HF and may be responsible for the pathogenetic mechanisms leading to the perpetuation of the pathophysiology and worsening of the HF signs and symptoms. There are biomarkers of activation of these neurohormonal pathways, such as the natriuretic peptides, catecholamine levels and neprilysin and various newer ones, which may be employed to better understand the mechanisms of HF drugs and also aid in defining the subgroups of patients who might benefit from specific therapies, irrespective of the degree of left ventricular dysfunction. These therapies are directed against these neurohumoral systems (neurohumoral antagonists) and classically comprise beta blockers, angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers and vaptans. Recently, the RAAS blockade has been refined by the introduction of the angiotensin receptor–neprilysin inhibitor (ARNI) sacubitril/valsartan, which combines the RAAS inhibition and neprilysin blocking, enhancing the actions of natriuretic peptides. All these issues relating to the neurohumoral activation in HF are herein reviewed, and the underlying mechanisms are pictorially illustrated. [ABSTRACT FROM AUTHOR]

Zekewos Demissie,1 Desalew Mekonnen2 1Department of Internal Medicine, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 2Department of Internal Medicine, Division of Cardiology, College of Health Sciences, Addis Ababa University, Addis Ababa, EthiopiaCorrespondence: Zekewos Demissie, Email zakdem61@gmail.comIntroduction: Optimal use of guideline-directed medical therapy (GDMT) is an important strategy in preventing cardiovascular morbidity and mortality from heart failure (HF). The use of beta blockers (BBs) is an important pillar of GDMT. The utilization and optimization of BBs are understudied in Ethiopia.Patients and Methods: A hospital-based cross-sectional study was conducted at the cardiology clinic of Tikur Anbessa Specialized Hospital on the utilization and optimization of BBs in the management of HFrEF patients from August 2022 to October 2022 G.C. Patients with a baseline HFrEF diagnosis and who had follow up for at least six months were included in the study. Patients were recruited during their routine clinic visit using systematic random sampling and consent was obtained from all participants. A total of 271 participants were included in this study. The optimal dose of BBs was predefined according to the 2021 European Society of Cardiology HF guideline. Data were collected through patients interview and reviewing the patient’s electronic medical records. The Collected Data was analysed using SPSS version 26.0.Results: The study found BB utilization in 214 (79%) patients. Among the patients taking BBs only 102 (37.6%) participants were on guideline-recommended BBs. The other 41% of patients taking BBs were on Metoprolol tartrate (34.7%) and Atenolol (6.6%), which are not guideline-recommended BBs and these findings signify underutilization of guideline-recommended BBs. Duration of treatment follow-up for more than 1 year, absence of peripheral edema, presence of atrial fibrillation and diuretic use were positively associated with BB utilization.Conclusion: Even though guideline-recommended BB at optimal doses exerts a clinical benefit, this study points out guideline-recommended BBs are underutilized and more importantly used at suboptimal doses among the study participants. To achieve the desired clinical benefit, physicians should attempt to provide guideline-recommended BBs at the optimum or maximum tolerable dose.Keywords: heart failure, beta blocker, Tikur Anbessa Specialized Hospital, optimal therapy

A sigmoid septum is associated with sharp angulation and aging of the aortic root; however, it does not affect the pressure gradient in the left ventricular outflow tract and is generally asymptomatic. This report describes a 73-year-old woman who presented with syncope after exertion. Echocardiography revealed that the cause was left ventricular outflow tract stenosis associated with a sigmoid septum; her symptoms improved with beta-blocker therapy. Exercise stress echocardiography was performed to determine treatment efficacy. Sigmoid septum causes syncope on exertion; however, drug therapy is effective. Exercise stress echocardiography is effective in determining treatment efficacy. If syncope is present, a sigmoid septum should be considered as a cause. 1. A sigmoid septum is part of or resembles hypertrophic cardiomyopathy, resulting in left ventricular outflow tract (LVOT) stenosis that is exacerbated by exertion and may cause syncope. 2. A sigmoid septum is a differential diagnosis for the cause of syncope and is diagnosed using cardiac echocardiography. 3. LVOT stenosis due to a sigmoid septum can be improved with drug therapy such as beta-blockers. 4. The effects of beta-blocker therapy can be determined by exercise stress echocardiography. [ABSTRACT FROM AUTHOR]

Atherosclerosis is characterized by the narrowing of the arterial lumen due to subendothelial lipid accumulation, with hypercholesterolemia being a major risk factor. Despite the recent advances in effective lipid-lowering therapies, atherosclerosis remains the leading cause of mortality globally, highlighting the need for additional therapeutic strategies. Accumulating evidence suggests that the sympathetic nervous system plays an important role in atherosclerosis. In this article, we reviewed the sympathetic innervation in the vasculature, norepinephrine synthesis and metabolism, sympathetic activity measurement, and common signaling pathways of sympathetic activation. The focus of this paper was to review the effectiveness of pharmacological antagonists or agonists of adrenoceptors (α1, α2, β1, β2, and β3) and renal denervation on atherosclerosis. All five types of adrenoceptors are present in arterial blood vessels. α1 blockers inhibit atherosclerosis but increase the risk of heart failure while α2 agonism may protect against atherosclerosis and newer generations of β blockers and β3 agonists are promising therapies against atherosclerosis; however, new randomized controlled trials are warranted to investigate the effectiveness of these therapies in atherosclerosis inhibition and cardiovascular risk reduction in the future. The role of renal denervation in atherosclerosis inhibition in humans is yet to be established. [ABSTRACT FROM AUTHOR]

Copyright of Ahi Evran Medical Journal is the property of Ahi Evran University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: Drug-drug interactions are sometimes neglected in oncology practice. Due to drug pharmacokinetic and pharmacodynamic interactions, clinically increased or decreased drug effects and increased or decreased adverse effects may occur. Considering that the concomitant use of these two drugs that affect vascular endothelial growth factor receptor (VEGFR) may cause pharmacological potentiation or additive interaction, we aimed to evaluate the survival outcomes of concomitant use of bevacizumab and beta blockers in patients with metastatic colorectal cancer (mCRC). Methods: In total, 181 patients with mCRC administered with bevacizumab plus cytotoxic chemotherapy regimen in a first-line setting were divided into two groups: concomitant beta-blocker user and nonuser. Results: The median overall survival (mOS) was 35.9 (95% CI: 27.9–43.9) months in the beta-blocker-using group and 29.6 (95% CI: 27.9–43.9) months in the beta-blocker-non-using group (p = 0.054). The median progression-free survival (mPFS) was 16.1 (95% CI: 12.4–19.9) months in the beta-blocker-using group and 12.8 (95% CI: 10.6–15.0) months in the beta-blocker-non-using group (p = 0.006). The multivariate analysis revealed that beta-blocker use was an independent predictor of mPFS (HR: 0.66, 95% CI: 0.46–0.93, p = 0.018) and mOS (HR: 0.57, 95% CI: 0.36–0.91, p = 0.02). Conclusion: This study demonstrated that concomitant usage of beta blockers improved both survival outcomes, irrespective of the kind of beta blocker. [ABSTRACT FROM AUTHOR]

This article discusses the hypothetical scenario of prescribing propranolol, a beta blocker, to an infant at risk of anaphylaxis who is also prescribed epinephrine auto-injectors. The concern is that the opposing effects of epinephrine and propranolol may have negative consequences. However, there is no evidence that patients on beta blockers require increased doses of epinephrine for anaphylaxis. In the event of anaphylaxis, it is important to administer epinephrine as quickly as possible, and if there is a suboptimal response, glucagon administration could be considered. Fatal outcomes from anaphylaxis in infants are extremely rare, and symptoms tend to be less severe in infants than in older children. The authors provide guidance on managing the prescription of propranolol and epinephrine auto-injectors in infants with food allergies. [Extracted from the article]

Combination antihypertensive treatments are usually used in everyday life, which has a life-threatening risk of using an overdose accidentally or suicidally. The effects of calcium channel blockers on the cardiovascular system are negative chronotropic, myocardial depression, decreasing atrioventricular signals, and vasodilatation. Beta blocker drugs are affected to beta receptors of catecholamines with competitively inhibition. Hypotension and bradycardia are the most common cardiac manifestations, and the others are arrhythmias, pulmonary edema, depression of the central nervous system. A previously healthy 4-year-old boy used accidentally 240 mg verapamil/4 mg trandolapril two pieces and 5 mg nebivolol one, at the time of admission his clinical condition was in cardiogenic shock. We successfully treated him with insulin-euglycemia/glucagon treatment, calcium, and lipid infusion therapy, plasmapheresis, and continuous venovenous hemodiafiltration without any sequels. The intoxication of calcium channel blockers and beta blocker drugs are rare but severe cases because of life-threatening.

Metoprolol is a medication commonly utilized in select patients to achieve a reduction in heart rate, systolic blood pressure, or other indications. A majority of metoprolol metabolism occurs via CYP2D6. Decreased expression of the CYP2D6 enzyme increases the concentration of metoprolol. Current pharmacogenomics guidelines by the Dutch Pharmacogenomics Working Group recommend slower titrations and dose decreases to minimize adverse effects from poor metabolizers or normal metabolizers taking concomitant medications that are strong inhibitors of CYP2D6 (phenoconverters). This study aimed to evaluate adverse effects such as bradycardia, hypotension, and syncope in patients who are expected to have absent CYP2D6 enzyme activity due to drug–drug or drug–gene interactions. The secondary aims of this study were to evaluate heart rate measurements for the included participants. Retrospective data were collected for individuals with CYP2D6 genotyping results obtained for clinical purposes. Three categories (CYP2D6 normal metabolizers, poor metabolizers, and phenoconverters) were assigned. A total of 325 participants were included. There was no statistically significant difference found in the primary composite outcome between the three metabolizer groups (p = 0.054). However, a statistically significant difference was identified in the incidences of bradycardia between the poor metabolizers and the normal metabolizers or phenoconverters (p < 0.0001). The average heart rates were 2.8 beats per minute (bpm) and 2.6 bpm lower for the poor metabolizer and phenoconverter groups, respectively, compared to the normal metabolizers (p < 0.0001 for both comparisons). This study further supports the role of genetic testing in precision medicine to help individualize patient care as CYP2D6 poor metabolizers taking metoprolol were found to have an increase in bradycardia. Additional research is needed to clarify the dose relationship in this drug–gene interaction. [ABSTRACT FROM AUTHOR]

Simple Summary: Concurrent platinum-based chemoradiotherapy (CRT) followed by maintenance treatment with the PD-L1 inhibitor durvalumab is the most effective therapy in unresectable stage III non-small-cell lung cancer (NSCLC). However, severe toxicity of this approach may lead to an unsatisfactory outcome. Cardiovascular diseases (CVD) may justify the use of sequential CRT to avoid severe adverse events and maintain satisfactory effectiveness. Ensuring that patients with CVD do not have a worse prognosis than patients without CVD is one of the goals of cardio-oncology. It is important that, after sequential CRT as personalized for patients with CVD, there is no increased mortality, and this is the first achievement of this study. Patients receiving beta-blockers and statins had lower all-cause mortality over 2, 3, and 4 years. The clear benefit of treatment with beta-blockers (in possible combination with statin) was confirmed in a subgroup of patients with CVD. The patients with CVD and indications for different cardiac therapy could live significantly longer if they received beta-blockers with or without statins during long-term follow-up. It may be a time to consider beta-blockers and statins as prevention strategy in patients undergoing CRT for NSCLC. The study was conducted in the era when maintenance immunotherapy with durvalumab was not available in clinical practice after chemoradiotherapy (CRT) in unresectable non-small-cell lung cancer (NSCLC). The main aim of the study was to check whether the presence of cardiovascular diseases (CVD) and their pharmacotherapy affects the overall survival (OS) in such NSCLC patients undergoing sequential CRT. The group of 196 patients were analyzed: 101 patients with CVD (51.53%) and 95 patients with other reasons of qualification for sequential CRT (decreased performance status, older age, and other non-cardiovascular co-morbidities). Although patients with CVD were more often in older age, and they more often experienced cardiac and nephrological complications (p < 0.05 for all), there was a statistically nonsignificant trend for lower all-cause mortality in patients with CVD. The lowest all-cause mortality was observed in patients treated with beta-blockers and statins after two (HR = 0.31; 95%CI: 0.1–0.98; p = 0.047), three (HR = 0.33; 95%CI: 0.13–0.81; p = 0.015) and even four (HR = 0.45; 95%CI: 0.22–0.97; p = 0.027) years of follow-up. The benefit in OS remained significant in 101 patients with CVD treated with beta-blockers (HR = 0.65; 95%CI: 0.43–0.99; p = 0.045), and eventually statin, throughout the whole follow-up (log-rank p < 0.05). Further prospective studies are necessary to confirm the role of beta-blockers and statins in reduction of mortality in NSCLC patients undergoing radical CRT. [ABSTRACT FROM AUTHOR]

Inflammatory pathways of Toll-like receptor 4 (TLR4) and NLRP3 inflammasome contribute to acute myocardial infarction (AMI) pathophysiology. The hypoxia‐inducible factor 1α (HIF-1α), however, is a key transcription factor related to cardioprotection. This study aimed to compare the influence of carvedilol and thyroid hormones (TH) on inflammatory and HIF-1α proteins and on cardiac haemodynamics in the infarcted heart. Male Wistar rats were allocated into five groups: sham-operated group (SHAM), infarcted group (MI), infarcted treated with the carvedilol group (MI + C), infarcted treated with the TH group (MI + TH), and infarcted co-treated with the carvedilol and TH group (MI + C + TH). Haemodynamic analysis was assessed 15 days post-AMI. The left ventricle (LV) was collected for morphometric and Western blot analysis. The MI group presented LV systolic pressure reduction, LV end-diastolic pressure elevation, and contractility index decrease compared to the SHAM group. The MI + C, MI + TH, and MI + C + TH groups did not reveal such alterations compared to the SHAM group. The MI + TH and MI + C + TH groups presented reduced MyD88 and NLRP3 and increased HIF-1α levels. In conclusion, all treatments preserve the cardiac haemodynamic, and only TH, as isolated treatment or in co-treatment with carvedilol, was able to reduce MyD88 and NLRP3 and increase HIF-1α in the infarcted heart. [ABSTRACT FROM AUTHOR]

In complex suicides, more than one suicide method is applied at the same time or one after the other. The most common complex suicide includes the ingestion of drugs combined with drowning. A case of acute intoxication by Bisoprolol and drowning is reported. The dead body of a 40-year-old woman was discovered on a river side, soon after her husband found a suicide note at home. In the woman's vehicle four empty boxes of Bisoprolol, a widely used beta blocker, were also found. Main autopsy findings were consistent with drowning and represented by plume of froth at the mouth and nostrils with frothy fluid also in the airways, water into the stomach, and a remarkable pulmonary edema as a result of fluid aspiration. Toxicological analyses were performed on peripheral blood, urine and gastric content samples using liquid and gas chromatography, coupled with mass spectrometry. Toxicological results were negative for ethanol and other common drugs of abuse. High levels of bisoprolol were found in blood (7.54 mg/L), far exceeding the therapeutic range, in the urine (1.14 mg/L), and gastric content (13.12 mg/L). Bisoprolol intoxication was assessed as a relevant contributing condition to the immediate cause of death represented by drowning. Although Bisoprolol would certainly have a heart-depressing effect, it is not possible to determine if the victim fell unconscious or if she simply collapsed into the water with a secondary drowning. [ABSTRACT FROM AUTHOR]

Objective: Recurrent intracerebral hemorrhage (ICH) poses a high risk for patients with cerebral cavernous malformations (CCMs). This study aimed to assess the influence of medication intake on hemorrhage risk in sporadic CCMs. Methods: From a database of 1,409 consecutive patients with CCM (2003-2021), subjects with sporadic CCMs and complete magnetic resonance imaging data were included. We evaluated the presence of ICH as a mode of presentation, the occurrence of ICH during follow-up, and medication intake, including beta blockers, statins, antithrombotic therapy, and thyroid hormones. The impact of medication intake on ICH at presentation was calculated using univariate andmultivariate logistic regression with age and sex adjustment. The longitudinal cumulative 5-year risk for (re-)hemorrhage was analyzed using the Kaplan-Meier curves and the Cox regression analysis. Results: A total of 1116 patients with CCM were included. Logistic regression analysis showed a significant correlation (OR: 0.520, 95% CI: 0.284-0.951, p = 0.034) between antithrombotic therapy and ICH as a mode of presentation. Cox regression analysis revealed no significant correlation betweenmedication intake and occurrence of (re-)hemorrhage (hazard ratios: betablockers 1.270 [95% CI: 0.703-2.293], statins 0.543 [95% CI: 0.194-1.526], antithrombotic therapy 0.507 [95% CI: 0.182-1.410], and thyroid hormones 0.834 [95% CI: 0.378-1.839]). Conclusion: In this observational study, antithrombotic treatment was associated with the tendency to a lower rate of ICH as a mode of presentation in a large cohort of patients with sporadic CCM. Intake of beta blockers, statins, and thyroid hormones had no effect on hemorrhage as amode of presentation. During the 5-year follow-up period, none of the drugs affected the further risk of (re-)hemorrhage. [ABSTRACT FROM AUTHOR]

Beta blockers (BB) reduce chronotropic response and exercise capacity in heart failure with preserved ejection fraction (HFpEF). To analyze the influence of BB on exercise performance and O 2 pulse increase as a surrogate for stroke volume in HFpEF. We retrospectively analyzed the influence of BB intake (yes: n = 48/no: n = 51) on peak oxygen uptake (VO 2peak), oxygen uptake efficiency slope (OUES), and increase of O 2 pulse in HFpEF patients undergoing cardiopulmonary exercise testing (CPET). Associations of outcome variables and risk category of the algorithm of the Heart Failure Association of the European Society of Cardiology (HFA-PEFF score) were calculated. Patients on BB showed lower VO 2peak (p =.003) and OUES (p =.002), with a dominant effect in the high-risk (p =.020; 0.002), but not in the low risk-group (p =.434; p =.499). In the intermediate group BB showed a trend towards lower VO 2peak (p =.078) and lower values for OUES (p =.020). Patients on BB also demonstrated a lower increase of O 2 pulse during exercise (p =.002), without differences between HFA-PEFF risk groups (low: p =.322, intermediate: p =.269, high: p =.313). BB reduce exercise capacity and O 2 pulse increase in HFpEF patients. Direct quantification of O 2 pulse increase may help to improve the discrimination of HFpEF patients. [Display omitted] • BB intake is associated with reduced exercise capacity in HFpEF patients. • BB intake reduces O 2 pulse increase as a surrogate for blunted stroke volume. • BB should be avoided in selected HFpEF patients. • Cardiopulmonary exercise testing contributes to characterize HFpEF phenotype [ABSTRACT FROM AUTHOR]

Background: Although glucagon use in beta blocker toxicity has been recommended for many years, evidence for its safety and efficacy in humans is limited. This study aims to determine the magnitude of effect of glucagon on heart rate (HR) and systolic blood pressure (SBP) in patients with suspected beta blocker toxicity and describe potential adverse effects of the medication. Methods: We conducted a retrospective, multi-center case series of patients greater than 12 years of age who received glucagon for suspected beta blocker toxicity. The primary outcome was the mean difference in HR from immediately pre- to 20-minutes post-glucagon administration. Secondary outcomes included the median difference in SBP, and occurrence of nausea, vomiting, and hyperglycemia. Results: A total of 107 patients met inclusion criteria accounting for 144 glucagon orders. The mean difference in HR from pre- to post-glucagon administration was 4 bpm ± 10.6 (95% CI [2.25–5.76], p < 0.001). The median difference (IQR) in SBP was 4.5 (− 6 to 16) mmHg (p = 0.004). Similar increases were observed when patients receiving concomitant vasopressors were excluded. A total of nine glucagon administrations (6.3%) were associated with nausea and 14 (9.7%) with vomiting; however, 52 doses (36.1%) were administered concomitantly with antiemetic medications. Fifteen administrations (10.4%) were associated with hyperglycemia. Conclusion: Glucagon administration was associated with a statistically significant increase in HR, but a small absolute difference of uncertain clinical significance. A similar observation was noted for SBP. Few patients experienced adverse events. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta blocker use in people with COPD is associated with a reduced risk of COPD exacerbations. The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease. Methods BICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV1

Acebutolol (ACE) is commonly used to treat hypertension and high blood pressure. Large doses of ACE can have adverse effects with potentially life-threatening consequences. It is, therefore, essential to develop a simple, low-cost, reliable, and reproducible device for detecting ACE in biofluids. This study explores the potential of unique two-dimensional nano-flakes, such as tungsten trioxide (WO 3). Graphene oxide (GO) typically exhibits lower electrical conductivity than pristine graphene due to the presence of oxygen-containing functional groups that interfere with the π-conjugated structure. Functionalizing GO with tannic acid (TA) can partially reinstate the π-conjugation and limit the amount of oxygen, resulting in enhanced electrical conductivity. Ultrasonic techniques were utilized to create WO 3 NFs@TA-rGO, and a range of spectroscopic and microscopic methods were applied to examine the formation of the resulting WO 3 NFs@TA-rGO nanocomposites. Under optimal conditions, modified sensors resulted in lower limits of detection (0.0055 μM) and good sensitivity (0.40 μA μM−1 cm−2). They also exhibited a broad linear range spanning from 0.009 to 568.6 μM. Fabricated sensors have significant anti-interference properties with high specificity and excellent storage stability (RSD = 4.3 %), reproducibility (RSD = 3.9 %), and repeatability (RSD = 3.3 %). Ultimately, the sensor's efficacy was confirmed through the successful detection of ACE in biological samples (with recoveries ranging from 99.1 to 99.6 %). Lastly, this study highlights the substantial potential of ACE detection and extends its applications in biomedical diagnostics and pharmaceutical research. Fabrication of WO 3 NFs @TA-rGO sensors for effectively detection of acebutolol in bio-fluids. [Display omitted] • The WO 3 NFs and TA-rGO nanocomposite - modified electrode was used for the investigation of ACE. • The electrochemical process of ACE was diffusion controlled. • The detection limit of ACE was determined to be 0.0055 μM and the linear range 0.009–568.6 μM. • ACE was analyzed in human serum and urine bio specimens with an impressive recovery of 99.2–99.6 %. [ABSTRACT FROM AUTHOR]

BackgroundIn patients with cirrhosis, portal hypertension increases intestinal permeability, dysbiosis, and bacterial translocation, promoting an inflammatory state that can lead to the progression of liver disease and development of hepatocellular carcinoma (HCC). We aimed to investigate whether beta blockers (BBs), which can mediate portal hypertension, conferred survival benefits in patients treated with immune checkpoint inhibitors (ICIs).MethodsWe conducted a retrospective, observational study of 578 patients with unresectable HCC treated with ICI from 2017 to 2019 at 13 institutions across three continents. BB use was defined as exposure to BBs at any time during ICI therapy. The primary objective was to assess the association of BB exposure with overall survival (OS). Secondary objectives were to evaluate the association of BB use with progression-free survival (PFS) and objective response rate (ORR) according to RECIST 1.1 criteria.ResultsIn our study cohort, 203 (35%) patients used BBs at any point during ICI therapy. Of these, 51% were taking a nonselective BB. BB use was not significantly correlated with OS (hazard ratio [HR] 1.12, 95% CI 0.9-1.39, P = 0.298), PFS (HR 1.02, 95% CI 0.83-1.26, P = 0.844) or ORR (odds ratio [OR] 0.84, 95% CI 0.54-1.31, P = 0.451) in univariate or multivariate analyses. BB use was also not associated with incidence of adverse events (OR 1.38, 95% CI 0.96-1.97, P = 0.079). Specifically, nonselective BB use was not correlated with OS (HR 0.94, 95% CI 0.66-1.33, P = 0.721), PFS (HR 0.92, 0.66-1.29, P = 0.629), ORR (OR 1.20, 95% CI 0.58-2.49, P = 0.623), or rate of adverse events (OR 0.82, 95% CI 0.46-1.47, P = 0.510).ConclusionIn this real-world population of patients with unresectable HCC treated with immunotherapy, BB use was not associated with OS, PFS or ORR.

Beta-blockers (BB) after traumatic brain injury (TBI) accelerate cognitive recovery weeks after injury. BBs also inhibit leukocyte (LEU) mobilization to the penumbral blood brain barrier (BBB) 48-h after TBI. It is unclear whether the latter effects persist longer and accompany the persistent cognitive improvement. We hypothesized that 2 wk of BB after TBI reduce penumbral BBB leukocyte-endothelial interactions. Thirty CD1 mice underwent TBI (controlled cortical impact, CCI: 6 m/s velocity, 1 mm depth, 3 mm diameter) or sham craniotomy followed by i.p. saline (NS) or propranolol (1, 2, 4 mg/kg) every 12 h for 14 d. On day 14, in vivo pial intravital microscopy visualized endothelial-LEU interactions and BBB microvascular leakage. Day 14 Garcia neurological test scores and animal weights were compared to preinjury levels reflecting concurrent clinical recovery. LEU rolling was greatest in CCI + NS when compared to sham (P = 0.03). 4 mg/kg propranolol significantly reduced postCCI LEU rolling down to uninjured sham levels (P = 0.03). LEU adhesion and microvascular permeability were not impacted at this time interval. Untreated injured animals (CCI + NS) scored lower Garcia neurological test and greater weight loss recovery at day 14 when compared to preinjury (P < 0.05). Treatment with higher doses of propranolol (2, 4 mg/kg), improved weight loss recovery (P < 0.001). LEU rolling alone, was influenced by BB therapy 14 d after TBI suggesting that certain penumbral neuroinflammatory cellular effects of BB therapy after TBI persist up to 2 wk after injury potentially explaining the pervasive beneficial effects of BBs on learning and memory. [ABSTRACT FROM AUTHOR]

Introduction: Guidelines recommend angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB)/angiotensin receptor neprilysin inhibitors (ARNI); beta blockers; and mineralocorticoid receptor antagonists (MRA) in patients with symptomatic heart failure and reduced left ventricular ejection fraction before consideration of primary prevention implantable cardioverter defibrillator (ICD). This study aims to investigate dispensing rates of guideline-directed medical therapy (GDMT) before and after primary prevention ICD implantation in New Zealand.Methods: All patients receiving a primary prevention ICD between 2009 and 2018 were identified using nationally collected data on all public hospital admissions in New Zealand. This was anonymously linked to national pharmaceutical data to obtain medication dispensing. Medications were categorised as low dose (<50% of target dose), 50-99% of target dose or target dose based on international guidelines.Results: Of the 1,698 patients identified, ACEi/ARB/ARNI, beta blockers and MRA were dispensed in 80.2%, 83.6% and 45.4%, respectively, prior to ICD implant. However, ≥50% target doses of each medication class were dispensed in only 51.8%, 51.8% and 34.5%, respectively. Only 15.8% of patients were receiving ≥50% target doses of all three classes of medications. In the 1,666 patients who survived 1 year after ICD implant, the proportions of patients dispensed each class of medications remained largely unchanged.Conclusion: Dispensing of GDMT was suboptimal in patients before and after primary prevention ICD implantation in New Zealand, and only a minority received ≥50% target doses of all classes of medication. Interventions are needed to optimise use of these standard evidence-based medications to improve clinical outcomes and avoid unnecessary device implantation. [ABSTRACT FROM AUTHOR]

Labetalol is a drug that exhibits both alpha and beta-adrenergic receptor-blocking properties. The American Heart Association/American Stroke Association (AHA/ASA) has recommended labetalol as an initial treatment option for the management of severe hypertension. The physiologically based pharmacokinetic (PBPK) model is an in silico approach to determining the pharmacokinetics (PK) of a drug by incorporating blood flow and tissue composition of the organs. This study was conducted to evaluate the primary reasons for the difference in PK after intravenous (IV) and oral administration in healthy and diseased (renal and hepatic) populations. A comprehensive literature search was done using two databases, PubMed and Google Scholar. Various PK parameters were screened for the development of the PBPK model utilizing a population-based PK-Sim simulator. Simulations were performed after creating building blocks firstly in healthy individuals and then in diseased patients after IV and oral administration. The disposition of labetalol after IV and oral administration occurring in patients with the hepatic and renal disease was predicted. The model was evaluated by calculating the Robs/pred ratio and average fold error (AFE), which was in the two-fold error range. Moreover, Box-whisker plots were made to compare the overall concentration of the drug in the body at various stages of disease severity. The presented model provides useful quantitative estimates of drug dosing in patients fighting against severe chronic diseases. [ABSTRACT FROM AUTHOR]

Postoperative atrial fibrillation is one of the most recognised complications of cardiac surgery. Although its exact pathophysiology remains unknown, evidence suggests that it is multifactorial and that it directly affects patient outcomes post cardiac surgery. It is associated with an increased risk of heart failure, renal failure, stroke and mortality. Pharmacological agents such as beta blockers and antiarrhythmic drugs are well established and extensively used for both the prevention and treatment of postoperative atrial fibrillation. This article will explore the pharmacological treatment of postoperative atrial fibrillation with specific reference to metoprolol and amiodarone, along with the pharmacokinetic and pharmacodynamic effects of both drugs. It will briefly discuss the evidence reviewed regarding the effectiveness of these drugs for postoperative atrial fibrillation and the recommendations from the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery on how postoperative atrial fibrillation should be treated. [ABSTRACT FROM AUTHOR]

Heart failure with reduced ejection fraction (LV-EF < 35%) is diagnosed in app. 11,000,000 patients worldwide. For the treatment of these patients, guideline directed medical therapy has proven to reduce mortality and rehospitalization regardless of the disease's etiology. It is implemented to treat clinical symptoms by improving the left ventricular ejection fraction. Patients with a transient risk of ventricular tachycardia and sudden cardiac death can be protected by a defibrillator vest. The defibrillator vest is capable to detect and terminate ventricular arrhythmias during Guideline Directed Medical Therapy (GDMT). It is based on the recommendations of the European society of cardiology for 3 months. Afterwards, the WCD wear time could be prolonged, or, in case of persistent low ejection fraction (LV-EF ≤ 35%), an implantable cardioverter defibrillator (ICD) should be implanted, as shown in the WEARIT-II-registry. Our goal was to evaluate the effects of GDMT on LV-recovery and reduction of ICD implantations under protection with a defibrillator vest—depending on the uptitration of GDMT. Methods: 339 consecutive patients between August 2017 and September 2020 with newly diagnosed cardiomyopathy and an EF ≤ 35% were analyzed retrospectively by chart review. All patients were protected by a wearable cardioverter defibrillator (WCD). GDMT as recommended by the ESC started at discharge from hospital. The left ventricular ejection fraction (LV-EF) was determined by transthoracic echocardiography at week 4, 8 and at week 12 (in case of prolonged WCD wear time). Uptitration was performed after 4 and 8 weeks during patient visits. We focused on baseline medication as per GDMT and the dosage increase at week 4, 8 and 12. The aim was the uptitration to the maximum dosage tolerated by the patient. We also compared the LV-EF improvement in the group with and without uptitration of medication dosage. Results: The patient age was, on average, 63.2 years (SD ± 11.9 years). A total of 129 pts (38%) had ICM, 196 (58%) had NICM (incl 66 pts (19%) with DCM and 51 pts (15%) with Myocarditis, 79 pts (24%) with unknown origin) and 14 pts (4%) had other entities (e.g., Tachycardiomyopathy). In total, 21 pts (6%) had an LV-EF of less than 16%, 130 pts (38%) between 16–25% and 183 pts (54%) between 26–35%. GDMT started at discharge from the hospital included treatment with beta blocker for 327 pts (96.5%), ACE-inhibitors/Angiotensin/ARNI for 283 pts (83.5%) and Mineralcorticoid receptor antagonists (MRA) for 334 pts (88.4%). Uptitration was performed in all groups at a rate of 82.3%, 91.1% and 81.0% after 4 weeks and 64.7%, 50.3% and 66.3% after 8 weeks, respectively. After 4 weeks, 25 pts (7.4%) and, after 8 weeks, 171 pts (50.4%) had an EF increase of 5% or more (mean 14.2%). After 4 weeks, 81 patients had an LV-EF more than 35%. A total of 169 pts had a wear time of 12 weeks and an improvement of LVEF of more than 35%. Interestingly, in our study we did not find a significant difference in LV-EF improvement between the group with no uptitration and the group with uptitration. Conclusions: Guideline-directed medical therapy under protection with a WCD from ventricular arrhythmia can reduce the need for implantation of an ICD and can lead to an improvement of ejection fraction. Interestingly, the LV-EF improvement depends on the GDMT at discharge. Current guidelines recommend an initiation of all therapy columns of GDMT (sacubitril/valsartan, ACE-inhibitor/AT1-blocker, mineralcorticoidreceptorblocker, beta blocker) at once and further uptitration to the maximal dosage (ESC Guidelines 2021). A further uptitration of all drugs of GDMT should lead to improvement of LV-EF and consequently to a reduction in ICD implantations. [ABSTRACT FROM AUTHOR]

Introduction: Covid 19 infection is a recent pandemic which has been linked numerous symptoms post recovery from acute illness. Inappropriate sinus tachycardia[IST] is one of the conditions seen in patients recovered from Covid 19 infection. Currently there is no effective treatment for IST. The present study compares the efficacy of Beta blockers and Ivabradine in controlling the heart rate in IST. Methods: A multi centric prospective study was carried out in 48 patients who developed Post COVID IST for a period of six months. The data was collected and analysed using appropriate statistical test for comparision of minimal, mean, and maximum heart rate at zero, three, and six months. RESULTs: The participants were divided into two random groups. Group A received Metoprolol 50 mg once daily and group B received Ivabradine 5 mg twice daily. Both the groups were followed and then their minimal, mean and maximal heart rate was recorded at zero, three and six months. Both the drugs were found to be effective in decreasing the heart rate with a p value of less than 0.05. Ivabradine was found to be superior than metoprolol in controlling mean heart rate over six months duration with a p value of less than 0.01.Ivabradine also had better effect than metoprolol in controlling maximal heart rate at three months with a p value of less than 0.01 and over six months with a p value of less than 0.001. Conclusion: Treatment of post COVID 19 IST with Ivabradine has shown to improve basal as well as mean heart rate and is more effective than Beta blocker for a long term use. It can be used as a better alternative to Beta blocker who developed its side effects or are intolerant to it. [ABSTRACT FROM AUTHOR]

Abstract Background Beta-adrenergic receptor blockers (BB) play an important role in the protection of organs that are susceptible for secondary injury due to stress-induced adrenergic surge. However, the use of BB in traumatic brain injury (TBI) patients is not yet the standard of care which necessitates clear scientific evidence to be used. The BBTBBT study aims to determine whether early administration of propranolol based on the high-sensitive troponin T(HsTnT) status will improve the outcome of TBI patients. We hypothesized that early propranolol use is effective in reducing 10- and 30-day mortality in TBI patients. Secondary outcomes will include correlation between serum biomarkers (troponin, epinephrine, cytokines, enolase, S100 calcium binding protein B) and the severity of injury and the impact of BB use on the duration of hospital stay and functional status at a 3-month period. Methods The BBTBBT study is a prospective, randomized, double-blinded, placebo-controlled three-arm trial of BB use in mild-to-severe TBI patients based on the HsTnT status. All enrolled patients will be tested for HsTnT at the first 4 and 6 h post-injury. Patients with positive HsTnT will receive BB if there is no contraindication (group 1). Patients with negative HsTnT will be randomized to receive either propranolol (group 2) or placebo (group 3). The time widow for receiving the study treatment is the first 24 h post-injury. Discussion Early BB use may reduce the catecholamine storm and subsequently the cascade of immune and inflammatory changes associated with TBI. HsTnT could be a useful fast diagnostic and prognostic tool in TBI patients. This study will be of great clinical interest to improve survival and functional outcomes of TBI patients. Trial registration ClinicalTrials.gov NCT04508244. Registered on 7 August 2020. Recruitment started on 29 December 2020 and is ongoing.