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Background: Beta‐blocker therapy, a treatment burdened by side effects including fatigue, erectile dysfunction and depression, was shown to reduce mortality and cardiovascular events after acute coronary syndromes (ACS) in the pre‐coronary reperfusion era. Potential mechanisms include protection from ventricular arrhythmias, increased ischaemia threshold and prevention of left ventricular (LV) adverse remodelling. With the advent of early mechanical reperfusion and contemporary pharmacologic secondary prevention, the benefit of beta‐blockers after ACS in the absence of LV dysfunction has been challenged. Methods: The present narrative review discusses the contemporary evidence based on searching the PubMed database and references in identified articles. Results: Recently, the REDUCE‐AMI trial—the first adequately powered randomized trial in the reperfusion era to test beta‐blocker therapy after myocardial infarction with preserved left ventricular ejection fraction (LVEF)—showed no benefit on the composite of all‐cause death or myocardial infarction over a median 3.5‐year follow‐up. While the benefit of beta‐blockers in patients with reduced LVEF remains undisputed, their value in post‐ACS patients with mildly reduced systolic function (LVEF 41%–49%) has not been studied in contemporary randomized trials; in this setting, observational studies have suggested a reduction in cardiovascular events with these agents. The adequate duration of beta‐blocker therapy remains unknown, but observational data suggests that any mortality benefit may be lost beyond 1–12 months after ACS in patients with LVEF >40%. Conclusion: We believe that there is sufficient evidence to abandon routine beta‐blocker prescription in post‐ACS patients with preserved LV systolic function. [ABSTRACT FROM AUTHOR]

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

Purpose: To evaluate systemic complications for timolol, carteolol, levobunolol, and/or betaxalol by using an FDA Federal Adverse Event Reporting System (FAERS) Methods: We evaluated FAERS for adverse events associated with β-blocker use for glaucoma. All reported symptoms were reviewed to identify systemic adverse events and to detect safety signals, defined as information on a new or known side effect that may be caused by a medicine. We used the proportional reporting ratio (PRR), reporting odds ratio (ROR), empirical Bayes geometric mean (EBGM), and information component (IC) as a part of a disproportionality analysis comparing the frequency of β-blocker symptoms with all other adverse event reports. We considered a signal to be detected when all four disproportionality analysis metrics were positive. Results: We found 10,500,309 total adverse event reports from the FAERS database 2004-2022Q3, which included 8,793 case reports with a primary suspect of a β-blocker use for glaucoma. 1,838 unique adverse symptoms were reported were associated with β-blocker. Regarding outcomes, there were 165 (1.88%) reports of disability, 671 (7.63%) reports of hospitalisation, and 1,934 (21.99%) reports of some other unspecified complication. Regarding adverse events, the most reported general, cardiac, and respiratory symptoms were respectively dizziness (n = 281), bradycardia (n = 145), and dyspnoea (n = 195). 256 (2.91%) cases of death were reported. We found significant signals on bradycardia (n = 145), complete atrioventricular block (n = 38), and bronchospasm (n = 23). No allergic, endocrine, constitutional, or gastrointestinal symptoms generated positive signals. Conclusion: β-blocker use in glaucoma therapy can be rarely associated with serious systemic and life-threatening complications. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion Beta‐blockers may inhibit neprilysin activity and conversely, neprilysin inhibition may have a sympatho‐inhibitory action. Consequently, sacubitril/valsartan may have a greater effect in patients not receiving a beta‐blocker compared to those treated with a beta‐blocker.We examined the effect of sacubitril/valsartan compared to enalapril on outcomes according to background beta‐blocker treatment in the 8399 patients with heart failure with reduced ejection fraction enrolled in PARADIGM‐HF. The primary outcome was time to first heart failure hospitalization or cardiovascular death. Compared to the 7811 patients taking a beta‐blocker, the 588 patients not receiving a beta‐blocker were older, more frequently female, but had a similar mean left ventricular ejection fraction and New York Heart Association class distribution, with little difference in N‐terminal pro‐B‐type natriuretic peptide. Patients not taking beta‐blockers had a higher rate of the primary endpoint than those taking beta‐blockers. The benefit of sacubitril/valsartan on the primary endpoint was evident in both the no beta‐blocker subgroup (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.45–0.82) and the beta‐blocker subgroup (HR 0.82, 95% CI 0.75–0.90; p‐interaction = 0.06). The respective HRs for cardiovascular death were 0.47 (95% CI 0.32–0.69) versus 0.84 (95% CI 0.75–0.95; p‐interaction <0.01) and for HF hospitalization 0.76 (95% CI 0.51–1.12) versus 0.80 (95% CI 0.71–0.90; p‐interaction = 0.73). For all‐cause death, the HR in the no beta‐blocker group was 0.50 (95% CI 0.36–0.71) compared to 0.89 (95% CI 0.80–0.99) in the beta‐blocker group (p‐interaction <0.01). Safety outcomes related to sacubitril/valsartan versus enalapril did not differ according to background beta‐blocker use.Sacubitril/valsartan may be more effective than enalapril in reducing the risk of death in patients not treated with a beta‐blocker compared to those treated with a beta‐blocker, but is effective regardless of beta‐blocker use.Clinical Trial Registration: ClinicalTrials.gov NCT01035255. [ABSTRACT FROM AUTHOR]

Background: Hospitalization of patients with heart failure makes it possible to optimize drug therapy, considerably improving the prognosis of this serious condition. Methods: We conducted a retrospective descriptive study of patients with reduced left ventricular ejection fraction (≤ 40%) in the Cardiology Department of a community hospital center in France to measure the prescription rate of heart failure medications in hospitalized patients with reduced ejection fraction heart failure and identify their limiting factors. The primary endpoint was the prescription on the discharge prescription of the following four drug classes: beta-blockers, renin–angiotensin–aldosterone system blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter inhibitors. Results: From September 1, 2022, to March 31, 2023, 73 patients were included in the study. About one-third of patients were discharged with the recommended four drug classes. Those discharged with all 4 drug classes were younger and had preserved renal function. Conclusions: The low rate of prescription of heart failure medications after hospitalization is a reminder of the need to develop a specialized follow-up structure to optimize the drug treatment of reduced ejection fraction heart failure, even in the most fragile patients. [ABSTRACT FROM AUTHOR]

Introduction: Early‐onset atrial fibrillation (AF) has already been observed in approximately 2% of patients with genetically proven long QT syndrome (LQTS). This frequency is higher than population‐based estimates of early‐onset AF. However, the concomitant expression of AF in LQTS is likely underestimated. The purpose of this study was to examine the clinical presentation, genetic background, and outcomes of a cohort of patients with LQTS and early‐onset AF referred to a single tertiary center. Methods: Twenty‐seven patients diagnosed with congenital LQTS were included in the study based on the documentation of early‐onset (age ≤50 years) clinical or subclinical AF episodes in all available medical records, including standard electrocardiograms, wearable monitor or cardiac implantable electronic devices. Results: Seventeen patients experienced clinical AF during the follow‐up period. Subclinical AF was detected in 10 patients through insertable or wearable cardiac monitors. In our series, the mean heart rate during AF episodes was found to be relatively low despite the patients' young age and the low or minimal effective doses of beta‐blockers used for QTc interval control. All patients exhibiting LQTS and early‐onset AF were genotype positive, carrying mutations in the KCNQ1 (66%), KCNH2, KCNE1, and SCN5A genes. Notably, most of these patients carried the same p.(R231C) mutation in the KCNQ1 gene (59%) and were from the same families, suggesting concurrent expression of familial AF and LQTS. Conclusion: LQTS patients are prone to developing clinical and subclinical AF, even at a younger age. The occurrence of early‐onset AF in the LQTS population could be more frequent than previously assumed. AF should be considered as a potential dysrhythmia related to LQTS. Our study emphasizes the importance of carefully researching clinical and/or subclinical episodes of AF through strict heart rhythm monitoring in the LQTS population. [ABSTRACT FROM AUTHOR]

Abstract Aims The efficacy of beta‐blockers in cardiac amyloidosis (CA) is unclear, and concerns persist that neurohormonal blockade could worsen symptoms of heart failure. We aimed to assess whether beta‐blocker therapy is associated with improved survival in patients with CA. Methods and results We conducted a systematic review and meta‐analysis to examine the impact of beta‐blocker therapy on mortality in patients with CA. A search of MEDLINE and EMBASE was performed in August 2023. Data were extracted from observational studies and synthesized with pooling and random effects meta‐analysis. Thirteen studies including 4215 patients with CA were incorporated in this review (3688 transthyretin amyloid cardiomyopathy (ATTR‐CM), 502 light chain amyloid cardiomyopathy (AL‐CM), 25 not specified; age 74.8 ± 5.5 years, 76% male). Over half of the cohort (52%) received beta‐blockers and the rate of beta‐blocker withdrawal was 28%. All‐cause mortality was 33% (range: 13–51%) after a median follow‐up ranging from 13 to 36 months. There was an inverse association between the pooled risk of mortality and the use of beta‐blocker therapy at any time point (RR 0.48, 95% CI 0.29–0.80, I2 = 83%, P = 0.005, seven studies). There was no association between mortality and beta‐blocker use (RR 0.65, 95% CI 0.29–1.47, I2 = 88%, P = 0.30) in the three studies that only included patients with ATTR‐CM. The three studies that included patients with both ATTR‐CM and AL demonstrated an association of beta‐blocker use with reduced mortality (OR 0.43, 95% CI 0.29–0.63, I2 = 4%, P

Abstract Background Hospitalization of patients with heart failure makes it possible to optimize drug therapy, considerably improving the prognosis of this serious condition. Methods We conducted a retrospective descriptive study of patients with reduced left ventricular ejection fraction (≤ 40%) in the Cardiology Department of a community hospital center in France to measure the prescription rate of heart failure medications in hospitalized patients with reduced ejection fraction heart failure and identify their limiting factors. The primary endpoint was the prescription on the discharge prescription of the following four drug classes: beta-blockers, renin–angiotensin–aldosterone system blockers, mineralocorticoid receptor antagonists, and sodium-glucose co-transporter inhibitors. Results From September 1, 2022, to March 31, 2023, 73 patients were included in the study. About one-third of patients were discharged with the recommended four drug classes. Those discharged with all 4 drug classes were younger and had preserved renal function. Conclusions The low rate of prescription of heart failure medications after hospitalization is a reminder of the need to develop a specialized follow-up structure to optimize the drug treatment of reduced ejection fraction heart failure, even in the most fragile patients.

Paragangliomas (PGs) are rare neuroendocrine tumors that originate in the autonomic nervous system. Functionally, they are highly vascular and may be parasympathetic or sympathetic. Parasympathetic tumors are usually asymptomatic and inactive, located mostly in the skull base in the distribution of IX and X cranial nerves. In contrast, sympathetic tumors are highly active (secretes norepinephrine) and symptomatic and mainly located in the abdomen and pelvic regions. Surgical removal of these tumors is curative and key to favorable outcomes. Some of these tumors have malignant potential as well. Meticulous preoperative preparation is needed but many patients may still land up in hypertensive crises intraoperatively which should be managed promptly and cautiously by the anesthesia team to reduce morbidity and mortality during surgery. Here, we describe the successful anesthetic management of a patient diagnosed with large aortocaval PG abutting the aorta and compressing the inferior vena cava and bilateral renal veins.

Abstract This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1β, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = − 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI. Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28–30, 2024, in Estoril, Lisbon, Portugal.

ABSTRACT Aims Methods and results Conclusions In the absence of randomized trial evidence, we performed a large observational analysis of the association between beta‐blocker (BB) use and clinical outcomes in patients with heart failure (HF) and mildly reduced (HFmrEF) and preserved ejection fraction (HFpEF).We pooled individual patient data from four large HFmrEF/HFpEF trials (I‐Preserve, TOPCAT, PARAGON‐HF, and DELIVER). The primary outcome was the composite of cardiovascular death or HF hospitalization. Among the 16 951 patients included, the mean left ventricular ejection fraction (LVEF) was 56.8%, and 13 400 (79.1%) had HFpEF (LVEF ≥50%). Overall, 12 812 patients (75.6%) received a BB. The median bisoprolol‐equivalent dose of BB was 5.0 (Q1–Q3: 2.5–5.0) mg with BB continuation rates of 93.1% at 2 years (in survivors). The unadjusted hazard ratio (HR) for the primary outcome did not differ between BB users and non‐users (HR 0.98, 95% confidence interval [CI] 0.91–1.05), but the adjusted HR was lower in BB users than non‐users (0.81, 95% CI 0.74–0.88), and this association was maintained across LVEF (pinteraction = 0.88). In subgroup analyses, the adjusted risk of the primary outcome was similar in BB users and non‐users with or without a history of myocardial infarction, hypertension, or a baseline heart rate <70 bpm. By contrast, a better outcome with BB use was seen in patients with atrial fibrillation compared to those without atrial fibrillation (pintreraction = 0.02).In this observational analysis of non‐randomized BB treatment, there was no suggestion that BB use was associated with worse HF outcomes in HFmrEF/HFpEF, even after extensive adjustment for other prognostic variables. [ABSTRACT FROM AUTHOR]

This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1β, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = − 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI. Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28–30, 2024, in Estoril, Lisbon, Portugal. [ABSTRACT FROM AUTHOR]

Tachycardia induces a reduction in the left ventricular ejection fraction (LVEF), which is defined as tachycardia-induced cardiomyopathy (TIC). Conversion to and maintenance of sinus rhythm by catheter ablation can improve LVEF in patients with TIC due to atrial fibrillation (AF). Beta-blockers are mandatory for the treatment of heart failure with reduced LVEF(HFrEF), but the necessity of beta-blockers in TIC patients even after catheter ablation remains unclear. We examined the effect of beta-blockers on cardiac function in TIC patients after catheter ablation. We retrospectively analyzed 124 patients with a history of heart failure and an LVEF of ≤ 50% who underwent catheter ablation for AF. TIC was defined as a ≥ 10% improvement in the baseline LVEF and an improvement to an LVEF of ≥ 50% at 6 months after ablation. Patients with other cardiomyopathy diagnosed before the ablation were excluded. LVEF was significantly increased with the reductions of the left ventricular and left atrial volumes at the 6-month follow-up in all 80 patients with TIC. No beta-blockers were prescribed during the post-ablation follow-up in 21 patients with TIC. The absolute values of and changes in the echocardiographic parameters between before and after ablation were not significantly different between patients with and without beta-blockers after the ablation. A simple score using the history of hospitalization for heart failure and use of beta-blockers or diuretics prior to ablation was useful in identifying TIC patients who did not need prescription of beta-blockers after catheter ablation. LVEF similarly improved in both patients with and without prescription of beta-blockers after the ablation. Beta-blockers may not need to be prescribed after successful catheter ablation for AF in LVEF of ≤ 50% patients without other cause of cardiomyopathy diagnosed before the ablation, a history of hospitalization for heart failure and prescription of beta-blockers and diuretics before the ablation. [ABSTRACT FROM AUTHOR]

Several guidelines do not recommend beta-blocker as the first-line treatment for hypertension because of its inferior efficacy in stroke prevention. Combination therapy with beta-blocker is commonly used for blood pressure control. We compared the clinical outcomes in patients treated with amlodipine plus bisoprolol (A + B), a ß1-selective beta-blocker and amlodipine plus valsartan (A + V). A population-based cohort study was performed using data from the Taiwan National Health Insurance Research Database. From 2012 to 2019, newly diagnosed adult hypertensive patients who received initial amlodipine monotherapy and then switched to A + V or A + B were included. The efficacy outcomes included all-cause death, atherosclerotic cardiovascular disease (ASCVD) event (cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization), hemorrhagic stroke, and heart failure. Multivariable Cox proportional hazards model was used to evaluate the relationship between outcomes and different treatments. Overall, 4311 patients in A + B group and 10980 patients in A + V group were included. After a mean follow-up of 4.34 ± 1.79 years, the efficacy outcomes were similar between the A + V and A + B groups regarding all-cause death (adjusted hazard ratio [aHR] 0.99, 95% confidence interval [CI] 0.83–1.18), ASCVD event (aHR 0.97, 95% CI 0.84–1.12), and heart failure (aHR 1.06, 95% CI 0.87–1.30). The risk of hemorrhagic stroke was lower in A + B group (aHR 0.70, 95% CI 0.52–0.94). The result was similar when taking death into consideration in competing risk analysis. The safety outcomes were similar between the 2 groups. There was no difference of all-cause death, ASCVD event, and heart failure in A + B vs. A + V users. But A + B users had a lower risk of hemorrhagic stroke. [ABSTRACT FROM AUTHOR]

We investigated the effects of maintaining beta-blockers on the day of surgery on the incidence of atrial fibrillation and postoperative acute kidney injury (AKI) in patients undergoing cardiac surgery. We conducted a multicentre prospective observational study with propensity matching on patients treated with beta-blockers. We collected their baseline patient characteristics, comorbidities, and operative and postoperative outcomes. The endpoints were postoperative atrial fibrillation and AKI after cardiac surgery. Of the 1789 included patients, propensity matching led to 583 patients in each group. Maintenance of beta-blockers was not associated with a reduced risk of atrial fibrillation (odds ratio: 0.86 [95% confidence interval 0.66–1.14], P =0.335; 141 patients [24.2%] vs 126 patients [21.6%]). Sensitivity analysis did not demonstrate association between beta-blocker maintenance and atrial fibrillation after cardiac surgery (odds ratio: 0.93 [95% confidence interval: 0.72–1.22], P =0.625). Maintenance of beta-blockers was associated with a higher rate of norepinephrine use (415 [71.2%] vs 465 [79.8%], P =0.0001) and postoperative AKI (124 [21.3%] vs 159 [27.3%], P =0.0127). No statistically significant difference was observed in ICU length of stay. Maintenance of beta-blockers on the day of surgery was not associated with a reduced incidence of postoperative atrial fibrillation. However, maintenance of beta-blockers was associated with increased usage of vasopressors, potentially contributing to adverse postoperative renal events. NCT04769752. [ABSTRACT FROM AUTHOR]

Beta-blockers exert cardioprotective effects against heart failure. However, variability in therapeutic responses is associated with ADRB1 variants. ADRB1 variants contribute to rate control and autonomic dysfunction. Persistent hyperadrenergic stimulation contributes to the impairment of the pacemaker (SA node). HCN4 significantly influenced the regulation of heart rate in the pacemaker. Exploring the effect of beta-blockers on pacemaker cells is expanding the view of their cardioprotective effects in heart failure. The objectives of this review were to identify ADRB1 variants affecting heart rate response in heart failure patients receiving beta-blocker treatment and to explore the effect of beta-blockers on HCN4/SA node. A systematic review was performed using three databases (Scopus, PubMed, and Science Direct). The inclusion criteria were English language and original manuscripts with relevant topics. The exclusion criteria were duplication and inaccessibility to the full text. Quality assessment tools were classified based on the use of research subjects and study designs, including NOS (cohort), SYRCLE (animal studies), and SciRAP (in vitro studies). Eight of 668 manuscripts were selected. This review found that ADRB1 variants (A145G(Ser49Gly) and C1165G(Arg389Gly)) can affect heart rate response in beta-blocker-treated heart failure. The percentage of patients with Ser49Ser- Gly389X (67%) who achieved the heart rate target was higher than that of the other haplotypes (48-52%). Among the responders, Arg389Arg required larger carvedilol equivalent daily doses of beta-blockers to reach the identical heart rate target than those with Gly389X (>50% (>25mg) versus ≤50% of the guideline-directed medical therapy (GDMT) target dose (≤25mg), respectively). In addition, this review found that beta-blockers demonstrated beneficial effects in regulating heart rate by inhibiting HCN-gated channels and improving channel regulation in the SA node. In general, this review provides important insights into beta-blockers in treating heart failure, specifically concerning the genetic variability of ADRB1 and the effect of betablockers on SA node/HCN4. [ABSTRACT FROM AUTHOR]

Purpose: Intradialytic hypertension affects 5–15% of hemodialysis patients, yet relevant studies are relatively scarce. It is also associated with higher interdialytic blood pressure. Beta-blockers can be preferred as antihypertensive drugs due to their superior blood pressure control, decreased risk of cardiovascular events, improved endothelial cell function, and decreased noradrenaline levels. Through this study, beta-blocker antihypertensive effects in intra- and interdialytic hypertension were analyzed. Methods: Systematic review and meta-analysis were performed following PRISMA guidelines. We registered our PROSPERO protocol (Registration ID: CRD42023446184) and included relevant full-text clinical trials or RCTs from 2008 to 2023 with predetermined keywords and criteria from multiple databases including PUBMED, COCHRANE, SCOPUS, and citation searching. Seven eligible articles were included in this review study. Results: Four studies with 82 participants for intradialytic hypertension evaluation were included. Meta-analysis showed a decrease in SBP in intradialytic hypertensive patients after beta-blocker intervention, with a significant estimated mean difference of − 15.19 mmHg (P < 0.00001; 95% CI − 19.47 to − 10.91). Supporting previous data, SBP remains constant between pre- and post-dialysis with beta-blocker therapy, with an insignificant estimated mean difference of − 2.72 mmHg (P = 0.29; 95% CI − 7.80 to 2.36). Whereas five studies with 142 participants were included for interdialytic hypertension evaluation. Meta-analysis shows a significant decrease in SBP before to after therapy, with an estimated mean difference of − 10.92 (P < 0.0001; 95% CI − 16.33 to − 5.51). Conclusion: Beta-blocker treatment resulted in significant reductions in post-hemodialysis systolic blood pressure among intra- and interdialytic hypertensive patients. [ABSTRACT FROM AUTHOR]

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

Anxiety is a critical component of the development and maintenance of drug addiction; however, anti-anxiety medications such as benzodiazepines and beta-blockers (β-adrenergic receptor antagonists) are not used for the treatment of substance use disorder, except for the management of acute withdrawal syndrome. Preclinical studies have shown that beta-blockers may reduce stress-induced relapse; however, the effect of beta blockers on the escalation and maintenance of drug intake has not been tested. To address this issue, we chronically administered the β-adrenergic receptor antagonist propranolol during the escalation or maintenance of cocaine intake in a model of extended access (6 h) to cocaine self-administration (0.5 mg/kg). The behavioural specificity of propranolol was tested using a non-drug reward (saccharin). Daily administration of propranolol (15 mg/kg) prevented the development of escalation of cocaine self-administration and partially reversed self-administration after the establishment of escalation of intake. Moreover, propranolol dose-dependently decreased the motivation for cocaine tested under a progressive ratio schedule of reinforcement during the development of escalation and after maintenance. Finally, propranolol administration had no effect on the escalation and maintenance of saccharin self-administration. These results demonstrate that chronic treatment with propranolol provides therapeutic efficacy in reducing cocaine self-administration during the development and after the establishment of escalation of cocaine self-administration in an animal model relevant to cocaine use disorder. These results suggest that beta blockers should be further investigated as a target for medication development for the treatment of cocaine use disorder.

The R-carvedilol enantiomer, present in the racemic mixture of the chiral drug carvedilol, does not bind to the β-adrenergic receptors, but exhibits skin cancer preventive activity. For skin delivery, R-carvedilol-loaded transfersomes were prepared using various ratios of drug, lipids, and surfactants, and characterized for particle size, zeta potential, encapsulation efficiency, stability, and morphology. Transfersomes were compared for in vitro drug release and ex vivo skin penetration and retention. Skin irritation was evaluated by viability assay on murine epidermal cells and reconstructed human skin culture. Single-dose and repeated-dose dermal toxicity was determined in SKH-1 hairless mice. Efficacy was evaluated in SKH-1 mice exposed to single or multiple ultraviolet (UV) radiations. Transfersomes released the drug at a slower rate, but significantly increased skin drug permeation and retention compared with the free drug. The transfersome with a drug-lipid-surfactant ratio of 1:3:0.5 (T-RCAR-3) demonstrated the highest skin drug retention and was selected for further studies. T-RCAR-3 at 100 µM did not induce skin irritation in vitro and in vivo. Topical treatment with T-RCAR-3 at 10 µM effectively attenuated acute UV-induced skin inflammation and chronic UV-induced skin carcinogenesis. This study demonstrates feasibility of using R-carvedilol transfersome for preventing UV-induced skin inflammation and cancer.

Purpose: Vascular endothelial growth factor (VEGF) inhibition is one of the cornerstones of treatment in the treatment of metastatic renal cell carcinoma (mRCC). Since RCC is a disease of advanced age and hypertension as a side effect of VEGF receptor inhibitors, beta-blocker use is common in these patients. We aimed to compare the treatment efficacy and survival results in case of concomitant use of these two drugs due to the inhibition of VEGF in beta-blockers. Methods: A total of 121 patients with a diagnosis of mRCC who used sunitinib or pazopanib in first-line therapy were included in the study. These patients were divided into two groups as those using concomitant beta-blockers and those not using them. Result: The median overall survival (mOS) of the patient using sunitinib or pazopanib and concomitant beta-blocker was 47 (95% CI 29.0–65.0) months, and the mOS of those not using concomitant beta-blocker was 18 (95% CI 8.9–27.1) months (p < 0.001). The median progression-free survival (mPFS) of the patients using sunitinib or pazopanib and concomitant beta-blocker was 20.4 (95% CI 4.5–40.1) months, and the mPFS of those not using it was 11.4 (95% CI 5.9–16.9) months (p = 0.042). Concomitant beta-blocker use was found to be a good prognostic factor for OS in the multivariate analysis (p = 0.029). In the multivariate analysis, concomitant beta-blocker use had a trend towards statistical significance for PFS (p = 0.062). Conclusion: Concomitant use of betablockers with sunitinib or pazopanib is associated with longer overall survial and progression free survival. [ABSTRACT FROM AUTHOR]

Cardiac complications after major noncardiac surgery are common and associated with high morbidity and mortality. How preoperative use of beta-blockers may impact perioperative cardiac complications remains unclear. In a multicentre prospective cohort study, preoperative beta-blocker use was ascertained in consecutive patients at elevated cardiovascular risk undergoing major noncardiac surgery. Cardiac complications were prospectively monitored and centrally adjudicated by two independent experts. The primary endpoint was perioperative myocardial infarction or injury attributable to a cardiac cause (cardiac PMI) within the first three postoperative days. The secondary endpoints were major adverse cardiac events (MACE), defined as a composite of myocardial infarction, acute heart failure, life-threatening arrhythmia, and cardiovascular death and all-cause death after 365 days. We used inverse probability of treatment weighting to account for differences between patients receiving beta-blockers and those who did not. A total of 3839/10 272 (37.4%) patients (mean age 74 yr; 44.8% female) received beta-blockers before surgery. Patients on beta-blockers were older, and more likely to be male with established cardiorespiratory and chronic kidney disease. Cardiac PMI occurred in 1077 patients, with a weighted odds ratio of 1.03 (95% confidence interval [CI] 0.94–1.12, P =0.55) for patients on beta-blockers. Within 365 days of surgery, 971/10 272 (9.5%) MACE had occurred, with a weighted hazard ratio of 0.99 (95% CI 0.83–1.18, P =0.90) for patients on beta-blockers. Preoperative use of beta-blockers was not associated with decreased cardiac complications including cardiac perioperative myocardial infarction or injury and major adverse cardiac event. Additionally, preoperative use of beta-blockers was not associated with increased all-cause death within 30 and 365 days. NCT02573532. [ABSTRACT FROM AUTHOR]

Aims: Guidelines recommend target doses (TD) of heart failure (HF) with reduced ejection fraction (HFrEF) medications regardless of sex. Differences in pharmacokinetics and pharmacodynamics may explain heterogeneity in treatment response, adverse reactions, and tolerability issues across sexes. The aim of this study was to explore sex‐based differences in the association between TD achievement and mortality/morbidity in HFrEF. Methods and results: Patients with HFrEF and HF duration ≥6 months registered in the Swedish HF Registry between May 2000 and December 2020 (follow‐up until December 2021) were analysed. Treatments of interest were renin–angiotensin system inhibitors (RASI) or angiotensin receptor–neprilysin inhibitors (ARNI), and beta‐blockers. Multivariable Cox regression models were performed to explore the risk of cardiovascular mortality or hospitalization for HF across dose categories in females versus males. A total of 17 912 patients were analysed (median age 77.0 years, interquartile range [IQR] 70.0–83.0), 29% were female. Over a median follow‐up of 1.33 years (IQR 0.29–3.22), for RASI/ARNI there was no significant difference in outcome for females achieving 50–99% versus 100% of TD (hazard ratio 0.92, 95% confidence interval 0.83–1.03), whereas males showed a gradual lowering in risk together with the achievement of higher % of TD (p‐interaction = 0.030). For beta‐blockers the achievement of TD was associated with the lowest risk of outcome regardless of sex. Conclusions: Our findings suggest that females and males might differently benefit from the same dose of RASI/ARNI, and do represent a general call for randomized controlled trials to consider sex‐specific up‐titration schemes when testing HFrEF treatments in need of up‐titration. [ABSTRACT FROM AUTHOR]

Background: Rate control is the most commonly employed first‐line management strategy for atrial fibrillation (AF) in patients with chronic kidney disease (CKD). Principal agents used to control heart rate (HR) include beta‐blockers (BB) and nondihydropyridine calcium channel blockers (ND‐CCB). However, there is a paucity of published studies of the differences between those drugs in CKD patients. Hypothesis: The present study aimed to investigate the differences, in terms of hospitalizations due to a poor HR control, in patients with AF under a rate‐control strategy according to glomerular filtration rate (GFR). Methods: The study cohort included 2804 AF patients under rate‐control regime (BB or ND‐CCB) between January 2014 and April 2020. The end point, determined by competing risk regression, was hospitalizations for AF with rapid ventricular response (RVR), slow ventricular response (SVR), and need for pacemaker. Results: On multivariate analysis, there were no statistical differences between ND‐CCB and BB for subjects with GFR > 60 mL/min/1.73 m2 (subdistribution heart rate [sHR] 0.850, 95% confidence interval [CI]: 0.61–1.19; p =.442) and GFR 30–59 mL/min/1.73 m2 (sHR 1.242, 95% CI: 0.80–1.63; p =.333), while in patients with GFR < 30 mL/min/1.73 m2, ND‐CCB therapy was associated with increased hospitalizations due to poor HR control (sHR 4.53, 95% CI: 1.19–17.18; p =.026). Conclusion: In patients with GFR ≥ 30 mL/min/1.73 m2, the choice of ND‐CCB or BB had no impact on hospitalizations due to poor HR control, while in GFR < 30 mL/min/1.73 m2, a possible association was detected. The effects of these drugs on GFR < 30 mL/min/1.73 m2 would require further investigation. Key points: Rate control is the most commonly employed first‐line management strategy for atrial fibrillation in patients with chronic kidney disease. Evidence to guide selection between beta‐blockers and nondihydropyridine calcium channel blockers is scarce.This is the first study to compare patients with atrial fibrillation under rate‐control strategy according to renal function.In patients with glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2, both nondihydropyridine calcium channel blockers (ND‐CCB) and beta‐blockers therapy have good results in heart rate (HR) control, while in advanced chronic kidney disease (GFR < 30 mL/min/1.73 m2), a possible association of ND‐CCB with increased hospitalizations due to poor HR control was detected. [ABSTRACT FROM AUTHOR]

Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a significant public health issue because of its increasing incidence and the substantial short-term and long-term burden it imposes. This burden includes high mortality rates, morbidity, and a significant impact on productivity and quality of life for survivors. During the management of TBI, extracranial complications commonly arise during the patient's stay in the intensive care unit. These complications can have an impact on both mortality and the neurological outcome of patients with TBI. Among these extracranial complications, cardiac injury is a relatively frequent occurrence, affecting approximately 25–35% of patients with TBI. The pathophysiology underlying cardiac injury in TBI involves the intricate interplay between the brain and the heart. Acute brain injury triggers a systemic inflammatory response and a surge of catecholamines, leading to the release of neurotransmitters and cytokines. These substances have detrimental effects on the brain and peripheral organs, creating a vicious cycle that exacerbates brain damage and cellular dysfunction. The most common manifestation of cardiac injury in TBI is corrected QT (QTc) prolongation and supraventricular arrhythmias, with a prevalence up to 5 to 10 times higher than in the general adult population. Other forms of cardiac injury, such as regional wall motion alteration, troponin elevation, myocardial stunning, or Takotsubo cardiomyopathy, have also been described. In this context, the use of β-blockers has shown potential benefits by intervening in this maladaptive process. β-blockers can limit the pathological effects on cardiac rhythm, blood circulation, and cerebral metabolism. They may also mitigate metabolic acidosis and potentially contribute to improved cerebral perfusion. However, further clinical studies are needed to elucidate the role of new therapeutic strategies in limiting cardiac dysfunction in patients with severe TBI. [ABSTRACT FROM AUTHOR]

Trial emulations in observational data analyses can complement findings from randomized clinical trials, inform future trial designs, or generate evidence when randomized studies are not feasible due to resource constraints and ethical or practical limitations. Importantly, trial emulation designs facilitate causal inference in observational data analyses by enhancing counterfactual thinking and comparisons of real-world observations (e.g. Mendelian Randomization) to hypothetical interventions. In order to enhance credibility, trial emulations would benefit from prospective registration, publication of statistical analysis plans, and subsequent prospective benchmarking to randomized clinical trials prior to their publication. Confounding by indication, however, is the key challenge to interpreting observed intended effects of an intervention as causal in observational data analyses. We discuss the target trial emulation of the REDUCE-AMI randomized clinical trial (ClinicalTrials.gov ID NCT03278509; beta-blocker use in patients with preserved left ventricular ejection fraction after myocardial infarction) to illustrate the challenges and uncertainties of studying intended effects of interventions without randomization to account for confounding. We furthermore directly compare the findings, statistical power, and clinical interpretation of the results of the REDUCE-AMI target trial emulation to those from the simultaneously published randomized clinical trial. The complexity and subtlety of confounding by indication when studying intended effects of interventions can generally only be addressed by randomization. [ABSTRACT FROM AUTHOR]

The tumor microenvironment influences cancer progression and response to treatments, which ultimately impacts the survival of patients with cancer. The sympathetic nervous system (SNS) is a core component of solid tumors that arise in the body. In addition to influencing cancer progression, a role for the SNS in the effectiveness of cancer treatments is beginning to emerge. This review explores evidence that the SNS impairs chemotherapy efficacy. We review findings of studies that evaluated the impact of neural ablation on chemotherapy outcomes and discuss plausible mechanisms for the impact of neural signaling on chemotherapy efficacy. We then discuss implications for clinical practice, including opportunities to block neural signaling to improve response to chemotherapy.

Abstract Objectives This study aimed to retrospectively assess cardiac autonomic activity in children with LQTS, considering genotype, symptoms, sex, age, and beta‐blocker therapy (BB) and compare it to healthy controls. Methods Heart rate variability (HRV), using power spectrum analysis, was analyzed in 575 Holter recordings from 116 children with LQTS and in 69 healthy children. The data were categorized into four age‐groups and four heart rate (HR) ranges. Results In LQT1 and LQT2, increasing HR corresponded to significantly lower low (LF) and high frequency (HF) compared to controls. Total power (PTOT) was lower in all LQT1 age‐groups compared to controls at HR 120–140 bpm (1–15 years: p

Background: This systematic review explores the effects of landiolol administration in individuals presenting with supraventricular tachyarrhythmia (SVT) and concurrent left ventricular dysfunction, without being septic or in a peri-operative period. Methods: We systematically searched PubMed, Cochrane, Web of Science, and Scopus databases, retrieving a total of 15 eligible studies according to prespecified eligibility criteria. Results: Patients treated with landiolol experienced a substantial reduction in heart rate (HR) (mean HR reduction: 42 bpm, 95% confidence intervals (CIs): 37–47, I2 = 82%) and were more likely to achieve the target HR compared to those receiving alternative antiarrhythmic therapy (pooled odds ratio (OR): 5.37, 95% CIs: 2.87–10.05, I2 = 0%). Adverse events, primarily hypotension, occurred in 14.7% of patients receiving landiolol, but no significant difference was observed between the landiolol and alternative antiarrhythmic receiving groups (pooled OR: 1.02, 95% CI: 0.57–1.83, I2 = 0%). No significant difference was observed between the two groups concerning sinus rhythm restoration (pooled OR: 0.97, 95% CI: 0.25–3.78, I2 = 0%) and drug discontinuation due to adverse events (pooled OR: 5.09, 95% CI: 0.6–43.38, I2 = 0%). Conclusion: While further research is warranted, this systematic review highlights the potential benefits of landiolol administration in the management of SVTs in the context of left ventricular dysfunction. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the utility of color Doppler ultrasonography in assessing infantile hemangioma response to treatment with oral propranolol. Method: A prospective study was conducted between January, 2016 and December, 2022, wherein children with symptomatic (ulceration, bleeding, pain and scarring) infantile hemangioma were given oral propranol (2 mg/kg per day in three divided doses) as outpatient therapy. The clinical response was assessed three months post-initiation of treatment (intermediate clinical response) and three months post-completion of treatment (final clinical response, FCR). The primary outcome measurement was a clinical and radiological response (resistivity index (RI), pulsatility index (PI) and peak systolic velocity) to treatment. The secondary outcomes assessed were the complications related to treatment. Result: Out of 601 patients who were started on propranolol, 99 developed severe adverse effects and were excluded from analysis. At FCR assessment, out of 502 participants, 64.3% (n = 323) showed excellent response, 17.7% (n = 89) showed partial, and 17.9% (n = 90) were non-responders. A significant increase in RI and PI values was noted in all children following propranolol treatment for six months. An increase > 7.5% in RI could identify responders with 92% sensitivity, 91% specificity and area under the curve (AUC) of 0.963. An increase of > 11.5% in PI could identify responders with 86% sensitivity, 91% specificity and AUC of 0.896. Patients initially showing no response but later becoming excellent responders had significantly higher RI and PI values. Conclusion: Color Doppler ultrasonography is a valuable tool in predicting the treatment outcome of infantile hemangioma using propranolol. [ABSTRACT FROM AUTHOR]

• Most patients (about 90 %) who develop heart failure (HF) have hypertension. • All drugs used in the treatment of heart failure lower blood pressure. • Heart failure patients in general have reduced systolic function. • The totality of evidence indicates no difference in drug treatment related to EF. • RASi or ARNI, MRA, beta-blocker and SGLT2i plus diuretics are used to treat HF patients. More than 90 % of patients developing heart failure (HF) have hypertension. The most frequent concomitant conditions are type-2 diabetes mellitus, obesity, atrial fibrillation, and coronary disease. HF outcome research focuses on decreasing mortality and preventing hospitalization for worsening HF syndrome. All drugs that decrease these HF endpoints lower blood pressure. Current drug treatments for HF are (i) angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor neprilysin inhibitors, (ii) selected beta-blockers, (iii) steroidal and non-steroidal mineralocorticoid receptor antagonists, and (iv) sodium-glucose cotransporter 2 inhibitors. For various reasons, these drug treatments were first studied in HF patients with a reduced ejection fraction (HFrEF). Subsequently, they have been investigated in HF patients with a preserved left ventricular ejection fraction (LVEF, HFpEF) of mostly hypertensive etiology, and with modest benefits largely assessed on top of background treatment with the drugs already proven effective in HFrEF. Additionally, diuretics are given on symptomatic indications. Patients with HFpEF may have diastolic dysfunction but also systolic dysfunction visualized by lack of longitudinal shortening. Considering the totality of evidence and the overall need for antihypertensive treatment and/or treatment of hypertensive complications in almost all HF patients, the principal drug treatment of HF appears to be the same regardless of LVEF. Rather than LVEF-guided treatment of HF, treatment of HF should be directed by symptoms (related to the level of fluid retention), signs (tachycardia), severity (NYHA functional class), and concomitant diseases and conditions. All HF patients should be given all the drug classes mentioned above if well tolerated. [ABSTRACT FROM AUTHOR]

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Ivabradine is a recently introduced inhibitor of the If ion channel, which exhibits the capacity to reduce heart rate while preserving hemodynamic stability. At present, ivabradine finds its clinical indication in patients suffering from heart failure with reduced ejection fraction and maintaining a relative sinus rhythm refractory to beta-blockers. To optimize heart rate control, it is recommended to pursue an aggressive up-titration of ivabradine. This approach may ameliorate tachycardia-induced hypotension by incrementally enhancing cardiac output and allow further up-titration of agents aimed at ameliorating heart failure, such as beta-blockers. Both the modulation of heart rate itself and the up-titration of agents targeting heart failure lead to cardiac reverse remodeling, consequently culminating in a subsequent reduction in mortality and morbidity. A novel overlap theory that our team proposed recently has emerged in recent times. Under trans-mitral Doppler echocardiography, the E-wave and A-wave closely juxtapose one another without any overlapping at the optimal heart rate. Employing echocardiography-guided ivabradine for heart-rate modulation to minimize the overlap between the E-wave and A-wave appears to confer substantial benefits to patients with heart failure. This approach facilitates superior cardiac reverse remodeling and yields more favorable clinical outcomes when compared to those patients who do not receive echocardiography-guided care. The next pertinent issue revolves around the potential expansion of ivabradine's clinical indications to encompass a broader spectrum of diseases. It is imperative to acknowledge that ivabradine may not yield clinically significant benefits in patients afflicted by heart failure with preserved ejection fraction, acute heart failure, sepsis, or stable angina. An important fact yet to be explored is the clinical applicability of ivabradine in patients with atrial fibrillation, a concern that beckons future investigation. In this review, the concept of overlap theory it introduced, along with its application to expand the indication of ivabradine and the overlap theory-guided optimal ivabradine therapy. [ABSTRACT FROM AUTHOR]

Purpose: Prophylactic beta-blockers are recommended to prevent postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). Polymorphisms in the beta-1 adrenergic receptor (ADRB1) and G protein-coupled receptor kinase 5 (GRK5) genes are associated with variable responses to beta-blockers. The aim of this study was to determine the clinical and genetic factors that influence the response to beta-blockers for POAF prophylaxis after CABG. Methods: Patients undergoing isolated CABG and receiving prophylactic beta-blockers (n = 249) were prospectively recruited and followed up for 6 postoperative days. Genotyping of ADRB1 rs1801253, and 3 GRK5 SNPs (rs3740563, rs10787959, and rs17098707) was performed. Results: Of the 249 patients, 52 patients (20.8%) experienced POAF. Age, hypertension, vasopressor use, calculated POAF risk score, GRK5 rs2230345 T-allele, and GRK5 rs3740563 A-allele were associated with POAF despite beta-blocker prophylaxis. The multivariate analysis revealed that age [odds ratio (OR) 1.06, 95% CI 1.02–1.11, p = 0.003] and GRK5 rs2230345 T-allele [OR 2.81, 95% CI 1.39–5.67, p = 0.004] were independent predictors of POAF after CABG despite beta-blocker prophylaxis. Conclusion: GRK5 rs2230345 T-allele carriers were less responsive than AA genotype carriers to prophylactic beta-blockers for the prevention of POAF after CABG. The study was registered on http://clinicaltrials.gov in March 2019, with trial registration number (TRN): NCT03871647. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical effectiveness of beta-blockers (BBs) and renin-angiotensin-aldosterone system (RAAS) inhibitors in chronic heart failure with preserved ejection fraction (HFpEF). Methods: 100 patients with HFpEF admitted to The Third Affiliated Hospital of Qiqihar Medical University, China, between April and June 2023 were stratified into five groups. Beta-blocker (BB) group received bisoprolol, angiotensin-converting enzyme inhibitor (ACEI) group received benazepril hydrochloride, angiotensin II receptor blocker (ARB) group received candesartan, angiotensin receptor neprilysin inhibitor (ARNI) group received sacubitril valsartan, and mineralocorticoid receptor antagonist (MRA) group received spironolactone. Differences in clinical effectiveness, six-minute walking distance (6MWD), cardiac functionality, quality of life, and survival rate were compared among the groups. Results: Beta-blocker group showed the highest efficacy. After treatment, all groups except MRA showed significant improvement in 6MWD. Also, ACEI, ARB, and ARNI groups exhibited significantly longer 6 MWD than MRA group (p < 0.05). Left ventricular ejection fraction levels showed significant improvement in the ACEI, ARNI, and MRA groups (p < 0.05), while pulmonary artery pressure (PAP) decreased in the BB, ACEI, ARNI, and MRA groups (p < 0.05). After treatment, the Minnesota Living with Heart Failure Questionnaire (MLHFQ) scores of BB, ACEI, ARB, and ARNI groups were significantly lower than before treatment (p < 0.05). All five groups significantly exhibited decline in NTproBNP levels after treatment (p < 0.05). However, at 18-month follow-up, there was no significant difference in survival rates among the groups (p > 0.05). Conclusion: Beta-blockers (BBs) and RAAS inhibitors show promising activity in HFpEF, bisoprolol enhances cardiac function, benazepril improves symptoms, candesartan aids exercise and sacubitril valsartan elevates cardiac class. However, none of these drugs significantly improves clinical outcomes. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the pregnancy outcome of patients taking beta-blockers for the treatment of maternal cardiac arrhythmias. Materials and Method: This study was a retrospective observational study involving 50 pregnant women with cardiac arrhythmias and 55 healthy pregnant women, admitted between January 1, 2020 and January 1, 2022, to Ankara City Hospital. Beta-blockers were classified into three groups: metaprolol, propranolol, and bisoprolol. The use of beta-blockers was examined in two groups: high-dose and low-dose. For pregnancy outcome, birth week, birth weight and birth weight Z-score, beta human chorionic gonadotrophin (bHCG) MoM and pregnancy-associated plasma protein A (PAPP-A) MoM, neonatal APGAR score, and neonatal intensive care unit admission (NICU) rates were determined. Results: The patient group taking beta-blockers had a statistically significant earlier delivery week than the group without beta-blocker use (p= <0.001). The rate of primary cesarean deliveries was higher in the study group (p= 0.007). Birth weight and APGAR score at the fifth minute was significantly lower in the study group, and NICU admission rate was significantly higher (p= 0.006, p= <0.001and p= <0.001, respectively). Conclusion: Beta-blockers, a first-line therapy for maternal arrhythmias, may affect fetal development and pregnancy outcomes. İt is recommended that these drugs to be administered are meticulously selected for appropriate subgroups, with lowest effective doses. [ABSTRACT FROM AUTHOR]

BACKGROUND More than 90% of patients developing heart failure (HF) have an epidemiological background of hypertension. The most frequent concomitant conditions are type 2 diabetes mellitus, obesity, atrial fibrillation, and coronary disease, all disorders/diseases closely related to hypertension. METHODS HF outcome research focuses on decreasing mortality and preventing hospitalization for worsening HF syndrome. All drugs that decrease these HF endpoints lower blood pressure. Current drug treatments for HF are (i) angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or angiotensin receptor neprilysin inhibitors, (ii) selected beta-blockers, (iii) steroidal and nonsteroidal mineralocorticoid receptor antagonists, and (iv) sodium-glucose cotransporter 2 inhibitors. RESULTS For various reasons, these drug treatments were first studied in HF patients with a reduced ejection fraction (HFrEF). However, subsequently, they have been investigated and, as we see it, documented as beneficial in HF patients with a preserved left ventricular ejection fraction (LVEF, HFpEF) and mostly hypertensive etiology, with effect estimates assessed partly on top of background treatment with the drugs already proven effective in HFrEF. Additionally, diuretics are given on symptomatic indications. CONCLUSIONS Considering the totality of evidence and the overall need for antihypertensive treatment and/or treatment of hypertensive complications in almost all HF patients, the principal drug treatment of HF appears to be the same regardless of LVEF. Rather than LVEF-guided treatment of HF, treatment of HF should be directed by symptoms (related to the level of fluid retention), signs (tachycardia), severity (NYHA functional class), and concomitant diseases and conditions. All HF patients should be given all the drug classes mentioned above if well tolerated. [ABSTRACT FROM AUTHOR]

Background Pulsus alternans has been considered a sign of poor prognosis in patients undergoing treatments for heart failure. However, it may be overlooked in patients with intra-aortic balloon pumps (IABPs). The use of IABP and ivabradine for a β-blocker introduction in a patient with dilated cardiomyopathy (DCM) and pulsus alternans and its consequence have never been reported. Case summary In a 16-year-old high school boy with idiopathic DCM [left ventricular end-diastolic diameter (LVDd), 72 mm; left ventricular ejection fraction (LVEF), 18%], the introduction of carvedilol therapy failed, causing cardiogenic shock under inotropes. Therefore, an IABP support was provided, and he was transferred to our hospital. The arterial pressure waveform under IABP demonstrated pulsus alternans with sinus tachycardia at 135/min. Ivabradine reduced the heart rate to ∼100/min and eliminated the pulsus alternans neither decreasing the cardiac index nor increasing the pulmonary artery wedge pressure. Subsequently, carvedilol was reintroduced, and IABP and inotropes were discontinued. Then, 112 days after his transfer to our hospital, left ventricular reverse remodelling was confirmed (LVDd, 54 mm; LVEF, 44%), and he returned to school. The carvedilol dose reached 20 mg/day in 4 months after discharge, and further improvement was observed a year after discharge (LVDd, 54 mm; LVEF, 52%). Discussion Pulsus alternans is considered a predictor of poor prognosis. However, IABP and ivabradine may stabilize the haemodynamics in pulsus alternans, leading to a successful β-blocker introduction. [ABSTRACT FROM AUTHOR]

BackgroundAlthough beta-blockers improve clinical outcomes in heart failure with reduced ejection fraction, the benefit of beta-blockers in heart failure with preserved ejection fraction (HFpEF) is uncertain. Global longitudinal strain (GLS) is a robust predictor of heart failure outcomes, and recent studies have shown that beta-blockers are associated with improved survival in those with low GLS (GLS

Abstract Introduction During ventricular pacing, a fusion of atrial activation may occur owing to the simultaneous retrograde conduction of the atrioventricular (AV) node and accessory pathway (AP), potentially leading to an inaccurate mapping of the atrial AP insertion site. Objective We tested the hypothesis that landiolol, an ultra‐short‐acting intravenous β1‐blocker, could dissociate a fusion of atrial activation. Methods We conducted a prospective before‐and‐after study to investigate the effect of landiolol on retrograde conduction via the AV node and AP. We enrolled 21 consecutive patients with orthodromic AV reciprocating tachycardia who underwent electrophysiological studies at our hospital between January 1, 2018, and August 31, 2020. Results Six patients exhibited a fusion of atrial activation. After landiolol administration (10 μg/kg/min), the effective refractory period was unchanged in AP (280 [240–290] ms vs. 280 [245–295] ms, p = .91), whereas that of the AV node was prolonged (275 [215–380] ms vs. 332 [278–445] ms, p = .03). The Wenckebach pacing rate via retrograde AV node decreased after landiolol administration (180 [140–200] beats per minute [bpm] vs. 140 [120–180] bpm, p = .02). Thus, landiolol decreased the minimum ventricular pacing rate required to dissociate a fusion of atrial activation (180 [160–200] bpm vs. 140 [128–155] bpm, p = .007). Radiofrequency catheter ablation under landiolol administration successfully eliminated AP in all patients during ventricular pacing without complications or recurrence. Conclusion Landiolol inhibited the AV node without affecting the AP and helped dissociate a fusion of atrial activation at a lower ventricular pacing rate.

IntroductionCompared with first-line antihypertensives, beta-blockers (BB) have been reported to lower the central aortic blood pressure suboptimally and are associated with increased stroke risk. This observation has not been investigated in hypertensives of African ancestry. We hypothesised that an individual patient data meta-analysis (IPD-MA) on the efficacy of second- or third-generation beta-blockers (STGBBs) in hypertensives of African descent may provide new insights.MethodsA single-stage IPD-MA analysed the efficacy of STGBB in lowering the mean arterial blood pressure and reducing the composite outcomes: cardiovascular death, stroke, and myocardial infarction.ResultsA total of 11,860 participants from four randomised control trials were included in the analysis. Second- or third-generation beta-blockers reduced the mean arterial pressure by 1.75 mmHg [95% confidence interval (CI):1.16–2.33; P < 0.001] in all participants included in the analysis, and by 1.93 mmHg (95% CI: 0.86–3.00; P < 0.001) in hypertensive Africans. In patients with established cardiovascular disease, where the benefits of BB therapy are well established, STGBBs were associated with an adjusted odds ratio of 1.33 (95% CI: 1.06–1.65; P = 0.015) of the composite outcome, most likely due to confounding. Similarly, the risk of total myocardial infarction was 1.76 times higher (95% CI: 1.15–2.68; P = 0.008) in hypertensives of African ancestry on STGBBs.ConclusionThe STGBBs reduced the mean arterial pressure comparably to other antihypertensives, and they were not associated with an increased risk of stroke.

Purpose: To present the potential mechanisms by which landiolol enhances a positive inotropic response in critically ill patients. Methods: Analysis of preclinical, animal, and clinical data to provide novel knowledge and translate research findings into potential clinical application. Results: The super-selective β1-antagonist landiolol may increase inotropy and may be associated with positive outcomes in critically ill patients with acute decompensated heart failure or sepsis. Conclusion: This review sheds light on the potential mechanisms by which landiolol enhances a positive inotropic response, potentially alleviating the long-held concern over possible negative hemodynamic effects in critically ill patients. [ABSTRACT FROM AUTHOR]

Aim: This study aims to compare the effectiveness of transjugular intrahepatic portosystemic shunt (TIPS) against combination therapy in the secondary prevention of esophageal variceal bleeding. Method: Literature search was conducted using 4 databases (PubMed, Cochrane, Ovid MEDLINE, and Ovid Embase) and individual hand searching. The selected studies were then critically appraised for their validity, importance, and applicability. Results: A total of 136 results were retrieved, and 2 systematic reviews and meta-analysis of randomized controlled trials (RCTs) were selected. Both studies showed that TIPS significantly decreased incidence of esophageal variceal rebleeding but had no significant effect on reducing overall mortality when compared to combination therapy. Study by Lin et al found that TIPS was significantly better than combination therapy for reducing mortality from variceal rebleeding, but study by Jing et al found no significant difference. Conclusion: TIPS is superior to combination therapy in reducing the incidence of esophageal variceal rebleeding. Nevertheless, its effectiveness in reducing mortality needs further investigation. Future research should look into its complications and cost-effectiveness in developing countries like Indonesia. [ABSTRACT FROM AUTHOR]

The value of biofeedback before elective coronary computed tomography angiography (CCTA) to reduce patients' heart rates (HR) was investigated in the current work. Sixty patients who received CCTA to exclude coronary artery disease were included in our study and separated into two groups: with biofeedback (W-BF) and without biofeedback (WO-BF). The W-BF group used a biofeedback device for 15 min before CCTA. HR was determined in each patient at four measurement time points (MTP): during the pre-examination interview (MTP1), positioning on the CT patient table before CCTA (MTP2), during CCTA image acquisition (MTP3), and after completing CCTA (MTP4). If necessary, beta-blockers were administered in both groups after MTP2 until a HR of less than 65 bpm was achieved. Two board-certified radiologists subsequently assessed the image quality and analyzed the findings. Overall, the need for beta-blockers was significantly lower in patients in the W-BF group than the WO-BF group (p = 0.032). In patients with a HR of 81–90, beta-blockers were not required in four of six cases in the W-BF group, whereas in the WO-BF group all patients needed beta-blockers (p = 0.03). The amount of HR reduction between MTP1 and MTP2 was significantly higher in the W-BF compared to the WO-BF group (p = 0.028). There was no significant difference between the W-BF and WO-BF groups regarding image quality (p = 0.179). By using biofeedback prior to elective CCTA, beta-blocker use could be decreased without compromising CT image quality and analysis, especially in patients with an initial HR of 81–90 bpm. [ABSTRACT FROM AUTHOR]

This Delphi method of consensus was designed to develop scientific statements for β-blockers in the continuum of cardiovascular diseases with a special focus on the role of bisoprolol. Eleven experienced cardiologists from across the Asia-Pacific countries participated in two rounds of the survey. In the first round, experts were asked to rate agreement/disagreement with 35 statements across seven domains regarding the use of β-blockers for treating hypertension, heart failure, coronary artery diseases, co-morbidities, as well as their safety profile, usage pattern, and pharmacokinetic variability. A consensus for a statement could be reached with >70% agreement. Except for seven statements, all attained consensus in the first round. In the second round that was conducted virtually, the experts re-appraised their ratings for the seven statements along with a critical appraisal of two additional statements that were suggested by experts in the preceding round. At the end of the second round, the final version included 36 statements (34 original statements, two statements suggested by experts, and the omission of one statement that did not attain consensus). The final version of statements in the second round was disseminated among experts for their approval followed by manuscript development. Attainment of consensus for almost all statements reconfirms the clinical benefits of β-blockers, particularly β1-selective blockers for the entire spectrum of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Introduction: During ventricular pacing, a fusion of atrial activation may occur owing to the simultaneous retrograde conduction of the atrioventricular (AV) node and accessory pathway (AP), potentially leading to an inaccurate mapping of the atrial AP insertion site. Objective: We tested the hypothesis that landiolol, an ultra‐short‐acting intravenous β1‐blocker, could dissociate a fusion of atrial activation. Methods: We conducted a prospective before‐and‐after study to investigate the effect of landiolol on retrograde conduction via the AV node and AP. We enrolled 21 consecutive patients with orthodromic AV reciprocating tachycardia who underwent electrophysiological studies at our hospital between January 1, 2018, and August 31, 2020. Results: Six patients exhibited a fusion of atrial activation. After landiolol administration (10 μg/kg/min), the effective refractory period was unchanged in AP (280 [240–290] ms vs. 280 [245–295] ms, p =.91), whereas that of the AV node was prolonged (275 [215–380] ms vs. 332 [278–445] ms, p =.03). The Wenckebach pacing rate via retrograde AV node decreased after landiolol administration (180 [140–200] beats per minute [bpm] vs. 140 [120–180] bpm, p =.02). Thus, landiolol decreased the minimum ventricular pacing rate required to dissociate a fusion of atrial activation (180 [160–200] bpm vs. 140 [128–155] bpm, p =.007). Radiofrequency catheter ablation under landiolol administration successfully eliminated AP in all patients during ventricular pacing without complications or recurrence. Conclusion: Landiolol inhibited the AV node without affecting the AP and helped dissociate a fusion of atrial activation at a lower ventricular pacing rate. [ABSTRACT FROM AUTHOR]

Patients taking beta-blockers (BBs) commonly experience weight gain. There is limited research exploring how BBs impact weight loss after bariatric surgery. We examined how BBs impact 12-month weight loss in patients undergoing sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). Large midwest health system. We reviewed health records of SG and RYGB patients (2011-2022) and categorized them by BB usage (none, pre-, post-, or pre- and postoperative). Multivariable linear regression models examined the relation between BB use, percent total body weight loss (%TBWL), and percent excess body mass index lost (%EBMIL). A total of 889 individuals (SG, n = 485; RYGB, n = 404) had complete data. RYGB led to greater %TBWL compared to SG (31% versus 26%, P <.01) and greater %EBMIL (79% versus 64%, P <.01). BB status did not significantly affect 12-month %TBWL or %EBMIL. BB use may not significantly affect weight loss 12 months after bariatric surgery. This finding could enable physicians to prescribe BBs for improved blood pressure control in bariatric surgery patients with less concern of blunting weight loss. Longer term follow-up with a larger sample size would be an important next step to better characterize the relationship between BB usage and bariatric surgery. • BB use does not impact %TBWL or %EBMIL 12 months after surgery. • Patients undergoing RYGB have greater 12-month %TBWL and %EBMIL. [ABSTRACT FROM AUTHOR]