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Abstract Background The prediction of maximal heart rate (MHR) and anaerobic threshold heart rate (HRAT) in patients with coronary heart disease (CHD), particularly among the Chinese population, remains a significant challenge. Existing equations for MHR prediction are primarily designed for healthy individuals not on medication for optimized β-blocker (BB) therapy, showing limited efficacy for individuals on various drug regimens. Moreover, the prediction of HRAT lacks established formulas. This study aims to develop equations for MHR and HRAT, assess the accuracy of historical MHR formulas, and examine their correlation with HR measurements at the anaerobic threshold (AT). Methods Among 2021 to 2023, 170 CHD patients were recruited. Patients were categorized into groups based on BB usage. BB dose was transformed into carvedilol dose. Multiple linear stepwise regression analysis was employed to identify predictors of MHR and HRAT, incorporating key patient variables according to prior studies (age, sex, height, weight, carvedilol dose, HRrest). The mean absolute percentage errors (MAPEs) were calculated and compared among abovementioned MHR and HRAT prediction formulas. Besides, the percentages of MHR in predicting HRAT among different formulas were calculated. Results For the patients with BB medication, the simplified equations derived for MHR and HRAT were 176 − 1.2*age + 0.7*HRrest − 0.4*weight and 98 − 0.6*age + 0.7*HRrest − 0.3*weight, respectively. For those without BB medication, the derived equations for MHR and HRAT were 200 − 1.1*age and 91 − 0.5*age + 0.5*HRrest, respectively. There are significant differences between the results predicted by the new formula and the prior formulas. The new formulas are helpful for predicting the MHR of patients during exercise more accurately and guiding exercise training more scientifically. Conclusions The new equations for estimating MHR and HRAT in CHD patients enhance the accuracy of prior formulas. Given the BB impact on sympathetic nerve activity, the predictive formulas for MHR and HRAT were significantly improved.

In this study, Bi2O3/TiO2 composite was successfully synthesised using the solvothermal method, and the morphology, composition, and surface area of the composite were determined. Comparisons of photocatalytic performance were performed using Bi2O3/TiO2 for the decomposition of Atenolol (ATN) a β-blockers that is generally used to treat disorders such as hypertension and arrhythmias, as a model contaminant under visible light irradiation. The effects of different parameters such as solution pH, catalyst dosage, initial ATN concentration, reaction time, coexisting cations and anions, and turbidity on the degradation efficiency of ATN were investigated. An excellent synergistic effect was observed in the decomposition of ATN with the simultaneous application of Bi2O3/TiO2 and LED compared to single processes (synergistic index value, 4.027). The Bi2O3 catalyst has a much lower photocatalytic performance for the decomposition of ATN than the synthesised Bi2O3/TiO2 composite. The optimal rate for pH, catalyst dosage, and initial concentration of ATN was 7, 400 mg/l and 10 mg/l, respectively. Under optimal conditions, about 68.92% and 22.58% of ATN were degraded after 60 minutes in the presence of Bi2O3/TiO2 and Bi2O3 catalysts, respectively. However, these efficiencies are reduced to 51.83% and 12.4%, respectively, under 50 NTU. The addition of co-existing anions, especially PO43⁻, remarkably reduced the efficiency of ATN removal in the Bi2O3/TiO2/LED process. The presence of cations promoted the degradation of ATN in the Bi2O3/LED process, while the efficiency of ATN degradation was inhibited by the presence of cations in the Bi2O3/TiO2/LED process. The ATN removal efficiency using LED irradiation (49.02%) was much higher than that of UV-C irradiation (27.16%) when the concentration of ATN was 30 mg/L. [ABSTRACT FROM AUTHOR]

While implantable cardioverter‐defibrillator (ICD) shocks are a lifesaving therapy, they can negatively affect the patient's quality of life. Amiodarone is commonly combined with β‐blockers (BB) in ICD recipients. However, this combination therapy's efficacy in preventing shocks compared to standard BB monotherapy is not well studied. The aim of this systematic review and meta‐analysis is to determine if combined amiodarone and BB therapy improves prevention of ICD shock delivery compared to BB monotherapy. We performed a comprehensive literature search using PubMed, Cochrane, and Web of Science databases, for studies that assess the impact of amiodarone and BB versus BB monotherapy in patients with an ICD. The primary outcome was a total number of ICD shocks delivered by the end of the study period. Four studies: three retrospective studies and one randomized controlled trial (RCT), with a total of 5818 patients with ICDs, were included in the analysis. Follow‐up periods ranged from 1 to 5 years. The combined amiodarone and BB group was not associated with a significantly lower number of ICD shocks compared to the BB monotherapy group (OR, 0.76; 95% CI, 0.44‐1.31; P =.32). A combination therapy of amiodarone and BB was not associated with any further reduction in ICD shocks, hospitalizations, or mortality. Additional RCTs are recommended to further validate our findings. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of β-blocker in patients with heart failure with preserved ejection fraction (HFpEF) remains to be determined. We aimed to clarify the association between the use of β-blocker and prognosis according to the status of frailty. Methods: We compared prognosis between HFpEF patients with and without β-blockers stratified with the Clinical Frailty Scale (CFS), using data from the PURSUIT-HFpEF registry (UMIN000021831). Results: Among 1159 patients enrolled in the analysis (median age, 81.4 years; male, 44.7%), 580 patients were CFS ≤ 3, while 579 were CFS ≥ 4. Use of β-blockers was associated with a worse composite endpoint of all-cause death and heart failure readmission in patients with CFS ≥ 4 (adjusted hazard ratio (HR) 1.43, 95% CI 1.10–1.85, p = 0.007), but was not significantly associated with this endpoint in those with CFS ≤ 3 (adjusted HR 0.95, 95% CI 0.71–1.26, p = 0.719) in multivariable Cox proportional hazard models. These results were confirmed in a propensity-matched analysis (HR in those with CFS ≥ 4: 1.42, 95% CI 1.05–1.90, p = 0.020; that in those with CFS ≤ 3: 0.83, 95% CI 0.60–1.14, p = 0.249), and in an analysis in which patients were divided into CFS ≤ 4 and CFS ≥ 5. Conclusions: Use of β-blockers was significantly associated with worse prognosis specifically in patients with HFpEF and high CFS, but not in those with low CFS. Use of β-blockers in HFpEF patients with frailty may need careful attention. [ABSTRACT FROM AUTHOR]

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.

OBJECTIVE: To systematically review the efficacy and safety of ivabradine ( IVA) combined with β-blockers in the treatment of chronic heart failure (CHF). METHODS: PubMed, Embase, the Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP and CBM were retrieved to collect randomized controlled trials of IVA combined with β-blockers in the treatment of CHF ( the observation group was treated with IVA combined with β-blocker, while the control group received β-blocker alone). The retrieval time was from the establishment of the database to Apr. 12th, 2023. Meta-analysis was performed by using RevMan 5. 4 and Stata 16 software. RESULTS: A total of 39 studies including 3 794 patients were enrolled. Meta-analysis showed that the total effective rate in the observation group was significantly higher than that in the control group, the heart rate was significantly lower than that in the control group, and the cardiac function indicator was significantly better than that in the control group ( left ventricular ejection fraction was higher than that in the control group, left ventricular end-systolic diameter and left ventricular end-diastolic diameter were lower than that in the control group, 6 min walking distance was longer than that in the control group), and the incidence of adverse reactions was significantly lower than that in the control group, with statistically significant differences (P < 0. 05). CONCLUSIONS: IVA combined with β-blocker has significant efficacy and good safety in improving the total effective rate, reducing heart rate and improving cardiac function in patients with CHF, which is worthy of clinical promotion and application. [ABSTRACT FROM AUTHOR]

BackgroundPatients with chronic obstructive pulmonary disease (COPD) after acute coronary artery syndrome (ACS) are at an increased risk of heart failure and death. However, β-blockers have been underused in this population group due to concerns of adverse reactions.ObjectiveThis study aims to investigate the β-blocker prescription at admission and its impact on the in-hospital outcomes in patients with COPD after ACS in a Chinese national cohort.MethodsAmong 113,650 patients with ACS enrolled in the national registry of the Improving Care for Cardiovascular Disease in China between November 2014 and July 2019, a total of 1,084 ACS patients with COPD were included in this study. The primary endpoint was in-hospital mortality, and the secondary endpoint was the composite of in-hospital all-cause death and heart failure.ResultsEarly oral β-blocker therapy was administered to 49.8% of patients. The Kaplan–Meier analysis showed that the early β-blocker treatment group had lower all-cause mortality (0.9% vs. 2.9%; P

Abstract Background Takotsubo cardiomyopathy (TCM) is a left ventricular dysfunction resembling acute coronary syndrome. Its prognosis is generally favorable; however, a subset of patients may present with severe complications. TCM is a rare side‐effect of modified electroconvulsive therapy (ECT); it has been reported in 22 female and two male patients. Eight cases of ECT reinitiation after TCM have been reported (all females), with the shortest duration being 3 weeks. Case Presentation We report the case of a 61‐year‐old man with a history of major depressive disorder and no history of heart disease or previous ECT treatment. Antidepressants had been ineffective, and ECT was indicated. After the third ECT session, the patient complained of chest pain and shortness of breath. Electrocardiography revealed ST elevation, and catheter angiography was used to diagnose TCM. The patient had mild heart failure but remained stable. Recognizing that ECT was effective, the patient asked for it to be reinitiated. We confirmed that the cardiac function had been normalized, applied a bisoprolol fumarate patch as a preventive measure, and reinitiated ECT 14 days after the onset of TCM. ECT was performed five times, with no recurrence of TCM and a marked improvement in depression. Conclusion We describe a male patient with major depressive disorder who underwent reinitiation of ECT 2 weeks after ECT‐induced TCM. Therefore, TCM should be recognized as a side‐effect of ECT, even in men. Moreover, depending on whether the patient's condition is stable, ECT can be successfully performed in patients with TCM.

Abstract Background Coronavirus disease 2019 (COVID‐19) sequelae, also known as long COVID, can present with various symptoms. Among these symptoms, autonomic dysregulation, particularly postural orthostatic tachycardia syndrome (POTS), should be evaluated. However, previous studies on the treatment of POTS complicated by COVID‐19 are lacking. Therefore, this study aimed to investigate the treatment course of long COVID complicated by POTS. Methods The medical records of patients who complained of fatigue and met the criteria for POTS diagnosis were reviewed. We evaluated the treatment days, methods and changes in fatigue score, changes in heart rate on the Schellong test, and social situation at the first and last visits. Results Thirty‐two patients with long COVID complicated by POTS were followed up (16 males; median age: 28 years). The follow‐up period was 159 days, and the interval between COVID‐19 onset and initial hospital attendance was 97 days. Some patients responded to β‐blocker therapy. Many patients had psychiatric symptoms that required psychiatric intervention and selective serotonin reuptake inhibitor prescription. Changes in heart rate, performance status, and employment/education status improved from the first to the last visit. These outcomes were believed to be because of the effects of various treatment interventions and spontaneous improvements. Conclusions Our study suggests that the condition of 94% of patients with POTS complicated by long COVID will improve within 159 days. Therefore, POTS evaluation should be considered when patients with long COVID complain of fatigue, and attention should be paid to psychological symptoms and the social context.

Infantile hemangioma (IH), a benign tumor of the vascular endothelium, is the most common type of vascular pathology of the infant’s skin, which grows and significantly increases in size mostly during the first 12 months of a child's life. Statistics indicate that IH affects up to 10% of newborns and children aged

Key summary points: Aim: To examine the effect of β-blockers on long-term cardiovascular mortality (CVM) in the oldest old (≥ 80 years) with acute myocardial infarction (AMI). Findings: β-blocker use at discharge had no significant association with long-term CVM in oldest old with AMI, which were further demonstrated by propensity score matching, inverse probability treatment weighting, and subgroup analyses. Message: This study first suggested β-blockers use in oldest old with AMI could not reduce post-discharge CVM, which need to be further verified by randomized controlled trials. Purpose: It is uncertain whether β-blockers are beneficial for long-term prognosis in older patients following acute myocardial infarction (AMI). Thus, this study sought to examine the effect of β-blockers on long-term cardiovascular mortality (CVM) in the oldest old (≥ 80 years) with AMI. Methods: In this prospective, consecutive, non-randomized study, a total of 1156 patients with AMI admitted within 24 h after onset of symptoms were enrolled from January 2012 to February 2020. Univariate and multivariate Cox regression analyses were performed to examine the impact of β-blocker use on prognosis. Furthermore, one-to-one propensity score matching (PSM) and inverse probability treatment weighting (IPTW) analyses were used to control for systemic differences between groups. The primary outcome was long-term CVM. Results: Among the enrolled subjects, 972 (85.9%) were prescribed with β-blockers at discharge. Over a mean follow-up of 26.3 months, 224 cardiovascular deaths were recorded. Both univariate [hazard ratio (HR), 1.41, 95% confidence interval (CI) 0.93–2.13] and multivariate (HR, 1.29, 95% CI 0.79–2.10) Cox regression analyses showed that β-blocker use had no significant association with the long-term CVM, which was further demonstrated by PSM (HR, 1.31, 95% CI 0.75–2.28) and IPTW (HR, 1.41, 95% CI 0.73–2.69) analyses. Subgroup analyses according to sex, heart rate, hypertension, diabetes, revascularization, left ventricular ejection fraction, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers use showed consistent results as well. Conclusion: Our findings first suggested that the use of β-blockers at discharge in oldest old with AMI was not useful for reducing post-discharge CVM, which need to be further verified by randomized controlled trials. [ABSTRACT FROM AUTHOR]

Introduction: Our study was conducted to determine factors associated with the effectiveness of a β-blocker eye drop add-on in altering pulse rate (PR) in glaucoma patients. Methods: This retrospective study examined 236 eyes of 138 patients who received a β-blocker eye drop add-on during follow-up. Patients were included if at least one PR measurement was available both before and after the add-on was started. We collected data on ophthalmic parameters: longitudinal PR; longitudinal choroidal blood flow, represented by laser speckle flowgraphy-measured mean blur rate (MBR); and diacron-reactive oxygen metabolites (d-ROMs). We used a multivariable linear mixed-effects model to investigate the effectiveness of the β-blocker eye drop add-on in altering PR and examined factors contributing to a larger PR alteration after the add-on was started by analyzing the effect on PR of the interaction term between the add-on and clinical factors. We used the k-means method to classify the patients. Results: The β-blocker eye drop add-on reduced PR (− 7.61 bpm, P < 0.001). Female gender, higher PR when the add-on was started, lower central corneal thickness, and a higher d-ROM level were associated with greater reduction in PR (P < 0.05). In a cluster of patients with these clinical features, choroidal MBR increased by + 3.42% when we adjusted for change over time; MD slope, which represents the speed of glaucoma progression, improved by + 0.64 dB/year (P < 0.05). Conclusions: We identified a glaucoma subgroup in which PR decreased, choroidal blood flow increased, and glaucoma progression slowed after a β-blocker eye drop add-on was started. [ABSTRACT FROM AUTHOR]

Bisoprolol is a beta blocker used for the treatment of high blood pressure. During the synthesis and scale up of Bisoprolol, several related compounds will be generated. In this article we have disclosed a facile preparative access to the chemical synthesis of five related compounds of Bisoprolol, namely, 3,3′-((methylenebis(4,1-phenylene))bis(oxy))bis(1-(isopropylamino) propan-2-ol) (2),(Bisoprolol Ph.Eur impurity-C), 3,3′-(((oxybis(methylene))bis(4,1-phenylene)) bis(oxy))bis(1-(isopropyl amino)propan-2-ol) (3), (Bisoprolol Ph.Eur impurity-D), (±) 2-(4-((2-isopropoxyethoxy)methyl)phenoxy)-3-(isopropylamino)propan-1-ol (4), (Bisoprolol Ph.Eur impurity-F), (±) 4-((3-isopropyl-2-oxooxazolidin-5-yl)methoxy)benzaldehyde (17) (Bisoprolol Ph.Eur impurity-T), (±) 5-((4-(hydroxymethyl)phenoxy)methyl)-3-isopropyloxazolidin-2-one (18) (Bisoprolol Ph.Eur impurity-U). These related compounds were listed in Pharmacopoeias and hence these impurities were synthesized and their structure was well established by modern analytical techniques like 1H-NMR, 13C-NMR, HRMS. These synthetic methodologies will be useful in the future for the synthesis of other related compounds and analogues of the Bisoprolol. [ABSTRACT FROM AUTHOR]

The benefits of improved clinical outcomes through blood pressure (BP) reduction have been proven in multiple clinical trials and meta-analyses. The new (2023) guideline from the European Society of Hypertension (ESH) includes β-blockers within five main classes of antihypertensive agents suitable for initiation of antihypertensive pharmacotherapy and for combination with other antihypertensive agents. This is in contrast to the 2018 edition of ESH guidelines that recommended β-blockers for use primarily in patients with compelling indications such as cardiovascular comorbidities, e.g. coronary heart disease, heart failure. This change was based on the fact that the magnitude of BP reduction is the most important factor for adverse cardiovascular outcomes, over and above the precise manner in which reduced BP is achieved. The ESH guideline also supports the use of β-blockers for patients with resting heart rate (>80 bpm); high resting heart rate is a sign of sympathetic overactivity, an important driver of adverse cardiac remodelling in the setting of hypertension and heart failure. Hypertension management guidelines support for the use of combination therapies for almost all patients with hypertension, ideally within a single-pill combination to optimise adherence to therapy. Where a β-blocker is prescribed, the inclusion of a dihydropyridine calcium channel blocker within a combination regimen is rational. These agents together reduce both peripheral and central BP, which epidemiological studies have shown is important for reducing the burden of premature morbidity and mortality associated with uncontrolled hypertension, especially strokes. [ABSTRACT FROM AUTHOR]

Stable angina, one manifestation of chronic coronary syndrome (CCS), is characterised by intermittent episodes of insufficient blood supply to the myocardium, provoking symptoms of myocardial ischaemia, particularly chest pain. These attacks usually occur during exercise or stress. Anti-ischaemic drugs are the mainstay of pharmacologic management of CCS with symptoms of angina. β-blockers reduce heart rate and myocardial contractility, thus reducing myocardial oxygen consumption. These drugs have been shown to ameliorate the frequency of anginal attacks and to improve exercise capacity in these patients. Current management guidelines include β-blockers as a first-line management option for most patients with CCS and symptoms of myocardial ischaemia, alongside dihydropyridine calcium channel blockers (CCB). The presence of comorbid angina and heart failure is a strong indication for starting with a β-blocker. β-blockers are also useful in the management of angina symptoms accompanied by a high heart rate, hypertension (with or without a renin-angiotensin-aldosterone-system [RAS] blocker or CCB), or microvascular angina (with a RAS blocker and a statin). A β-blocker is not suitable for a patient with low heart rate (<50 bpm), although use of a β-blocker may be supported by a pacemaker if the β-blocker is strongly indicated) and should be used at a low dose only in patients with low blood pressure. [ABSTRACT FROM AUTHOR]

Aim To explore the preventive effect and potential mechanism of β-blockers in vascular aging of spontaneously hypertensive rat (SHR). Methods 24 three-month-old male spontaneously hypertensive rats were randomly divided into placebo group, nifedipine group, nifedipine+metoprolol group and metoprolol group, treated with edible starch, 60 mg nifedipine sustained-release tablets, 40 mg nifedipine sustained-release tablets+75 mg metoprolol sustainedrelease tablets and 150 mg metoprolol sustained-release tablets, respectively. The rats fed with common diets for 9 months, and the blood pressure, heart rate and other general condition of the rats were dynamically measured. HE staining was used to observe the morphological characteristics of femoral aorta in rats. The vasomotor function of isolated femoral artery was tested by circumferential perfusion, immunofluorescence histological staining and real-time polymerase chain reaction (RT-PCR) were used to determine the expression of aging related genes p53 and p21, as well as endoplasmic reticulum stress related genes CHOP and XBP1. Results Compared with placebo group, systolic blood pressure decreased by about 30%, diastolic blood pressure decreased by about 20%, and heart rate decreased by 9%, 36% and 41% (all P<0. 01) in nifedipine group, nifedipine+metoprolol group and metoprolol group, respectively. Compared with placebo group, the systolic and diastolic functions of nifedipine group, nifedipine+metoprolol group and metoprolol group were significantly improved and the intima-media thickness decreased by 24%, 14% and 37% (all P<0. 01), respectively. Compared with nifedipine group and nifedipine+metoprolol group, the systolic and diastolic functions of metoprolol group were significantly improved and the intima-media thickness decreased by 18% and 27% (all P<0. 01), respectively. Compared with the placebo group, the expression levels of p53 protein, p53 mRNA, p21 protein, p21 mRNA, CHOP protein, CHOP mRNA, XBP1 protein and XBP1 mRNA in nifedipine group decreased by 35% (P<0. 01), 23% (P<0. 05), 25% (P<0. 01), 3% (P>0. 05), 51% (P<0. 01), 24% (P>0. 05), 21% (P<0. 01) and 23% (P>0. 05), the nifedipine+metoprolol group decreased by 36% (P<0. 01), 42% (P<0. 01), 4% (P>0. 05), 24% (P<0. 05), 32% (P<0. 01), 44% (P<0. 05), 13% (P<0. 01) and 42% (P<0. 05), the metoprolol group decreased by 47% (P<0. 01), 43% (P<0. 01), 42% (P<0. 01), 49% (P<0. 01), 78% (P<0. 01), 56% (P< 0. 01), 32% (P<0. 01) and 81% (P<0. 01). Compared with nifedipine group and nifedipine+metoprolol group, metoprolol group further inhibited the expression of genes related to aging and endoplasmic reticulum stress. Conclusions The arteries of spontaneously hypertensive rats show significant aging. β-blockers are better than calcium channel blockers in inhibiting vascular aging of spontaneously hypertensive rats, and at high doses β-blockers improve the degree of vascular aging better than combination therapy, and their mechanism may be related to the inhibition of endoplasmic reticulum stress. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 (COVID‐19) sequelae, also known as long COVID, can present with various symptoms. Among these symptoms, autonomic dysregulation, particularly postural orthostatic tachycardia syndrome (POTS), should be evaluated. However, previous studies on the treatment of POTS complicated by COVID‐19 are lacking. Therefore, this study aimed to investigate the treatment course of long COVID complicated by POTS. Methods: The medical records of patients who complained of fatigue and met the criteria for POTS diagnosis were reviewed. We evaluated the treatment days, methods and changes in fatigue score, changes in heart rate on the Schellong test, and social situation at the first and last visits. Results: Thirty‐two patients with long COVID complicated by POTS were followed up (16 males; median age: 28 years). The follow‐up period was 159 days, and the interval between COVID‐19 onset and initial hospital attendance was 97 days. Some patients responded to β‐blocker therapy. Many patients had psychiatric symptoms that required psychiatric intervention and selective serotonin reuptake inhibitor prescription. Changes in heart rate, performance status, and employment/education status improved from the first to the last visit. These outcomes were believed to be because of the effects of various treatment interventions and spontaneous improvements. Conclusions: Our study suggests that the condition of 94% of patients with POTS complicated by long COVID will improve within 159 days. Therefore, POTS evaluation should be considered when patients with long COVID complain of fatigue, and attention should be paid to psychological symptoms and the social context. [ABSTRACT FROM AUTHOR]

Abstract Background Diabetes mellitus (DM) and hypertension are well-known atherosclerosis risk factors. Furthermore, renal dysfunction is a crucial risk factor for patients with coronary artery disease (CAD), and managing renal function in these patients is complicated because of comorbid conditions and potential side effects during treatment. Therefore, this study aimed to investigate the effect of medications for hypertension on renal function after percutaneous coronary intervention (PCI) between patients with and without DM with statins. Methods In 297 consecutive patients undergoing PCI for stable angina pectoris, cystatin C (CysC) was evaluated at baseline and 9 months after PCI, and the percent change in CysC (%CysC) was calculated. The association of worsening renal function (WRF: %CysC ≥ 0) and baseline characteristics, including medications, was assessed. Results Among 297 hypertensive patients with statins, 196 and 101 were with and without DM, respectively. Angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker, and β-blocker were prescribed in 56 (29%), 82 (42%), and 91 (46%) patients in the DM group, and 20 (20%), 52 (51%), and 52 (51%) in the non-DM group, respectively. The patients with WRF after PCI were 100 (51%) and 59 (58%) in the DM and non-DM groups (p = 0.261). Additionally, the %CysC had no significant differences between groups [median: 0%, interquartile range (IQR): -7.9% to 8.5% vs. median: 1.1%, IQR: -6.6% to 9.6%, p = 0.521]. Multivariate logistic analysis for WRF using relevant factors from univariate analysis showed that only β-blocker [odds ratio (OR): 2.76, 95% confidence interval (CI): 1.03–7.90, p = 0.048] was independently associated with WRF in the DM group whereas ACEI (OR: 0.07, 95% CI: 0.01–0.47, p = 0.012) was negatively correlated with WRF in the non-DM group. Conclusion The β-blocker was the independent risk factor for WRF in patients with DM in the late phase after PCI for stable angina pectoris, while the use of ACEI had a renoprotective effect in patients without DM.

BackgroundThere are limited data available on the impact of early (within 24 h of admission) β-blocker therapy on in-hospital outcomes of patients with ST-elevation myocardial infarction (STEMI) and mild-moderate acute heart failure. This study aimed to explore the association between early oral β-blocker therapy and in-hospital outcomes.MethodsInpatients with STEMI and Killip class II or III heart failure from the Improving Care for Cardiovascular Disease in China project (n = 10,239) were enrolled. The primary outcome was a combined endpoint composed of in-hospital all-cause mortality, successful cardiopulmonary resuscitation after cardiac arrest, and cardiogenic shock. Inverse-probability-of-treatment weighting, multivariate Cox regression, and propensity score matching were performed.ResultsEarly oral β-blocker therapy was administered to 56.5% of patients. The incidence of the combined endpoint events was significantly lower in patients with early therapy than in those without (2.7 vs. 5.1%, P < 0.001). Inverse-probability-of-treatment weighting analysis demonstrated that early β-blocker therapy was associated with a low risk of combined endpoint events (HR = 0.641, 95% CI: 0.486-0.844, P = 0.002). Similar results were shown in multivariate Cox regression (HR = 0.665, 95% CI: 0.496-0.894, P = 0.007) and propensity score matching (HR = 0.633, 95% CI: 0.453-0.884, P = 0.007) analyses. A dose-response trend between the first-day β-blocker dosages and adverse outcomes was observed in a subset of participants with available data. No factor could modify the association of early treatment and the primary outcomes among the subgroups analyses.ConclusionBased on nationwide Chinese data, early oral β-blocker therapy is independently associated with a lower risk of poor in-hospital outcome in patients with STEMI and Killip class II or III heart failure.

Melanoma is an aggressive skin cancer. Increasing evidence has shown the role of β-adrenergic receptors in the pathogenesis of melanoma. Carvedilol is a widely used non-selective β-AR antagonist with potential anticancer activity. The purpose of the study was to estimate the influence of carvedilol and sorafenib alone and in combination on the growth and inflammatory response of C32 and A2058 melanoma cells. Furthermore, this study also aimed to predict the probable interaction of carvedilol and sorafenib when administered together. Predictive study of the interaction of carvedilol and sorafenib was performed using the ChemDIS-Mixture system. Carvedilol and sorafenib alone and in combination showed a growth inhibitory effect on cells. The greatest synergistic antiproliferative effect on both cell lines was observed at Car 5 μM combined with Sor 5 μM. Analysis in silico identified diseases, proteins, and metabolic pathways that can be affected by the interaction of carvedilol and sorafenib. The results obtained demonstrated that carvedilol and sorafenib modulated the secretion of IL-8 by IL-1β-stimulated by melanoma cell lines but the use of a combination of both drugs did not intensify the effect. In summary, the results presented indicate that the combination of carvedilol and sorafenib may have a promising anticancer effect on melanoma cells.

Purpose: To investigate the treatment persistence of carteolol hydrochloride/latanoprost fixed-combination ophthalmic solution (CAR/LAT) and other β-blocker/prostanoid FP receptor agonist fixed-combination ophthalmic solutions (BB/FP) in the treatment of glaucoma. Study design: Retrospective observational cohort study. Methods: A retrospective observational cohort study using JMDC Claims Database. Patients aged 20 years or older diagnosed with glaucoma between February 1, 2017, and March 31, 2020, and prescribed CAR/LAT or another BB/FP were included. Results: A total of 16,612 patients (7423 in the CAR/LAT group and 9189 in the other BB/FP group) were included. The cumulative treatment persistence rate at the end of follow-up was 42.0% (64.9% at 1 year, 53.4% at 2 years, 45.0% at 3 years, and 42.0% at 4 years) in the CAR/LAT group and 34.7% (54.8% at 1 year, 43.6% at 2 years, 37.1% at 3 years, and 34.7% at 4 years) in the other BB/FP group. Treatment persistence was significantly longer in the CAR/LAT group compared to that in the other BB/FP group (hazard ratio 0.747, p < 0.0001). Over the treatment period, the number of patients who discontinued treatment was 3281 (44.2%) in the CAR/LAT group and 4926 (53.6%) in the other BB/FP group; the median duration of treatment was 135 days and 97 days, respectively. Conclusion: The study results suggest that persistence rates vary depending on the BB/FP and CAR/LAT appears to be more persistent than other BB/FP. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) and hypertension are well-known atherosclerosis risk factors. Furthermore, renal dysfunction is a crucial risk factor for patients with coronary artery disease (CAD), and managing renal function in these patients is complicated because of comorbid conditions and potential side effects during treatment. Therefore, this study aimed to investigate the effect of medications for hypertension on renal function after percutaneous coronary intervention (PCI) between patients with and without DM with statins. Methods: In 297 consecutive patients undergoing PCI for stable angina pectoris, cystatin C (CysC) was evaluated at baseline and 9 months after PCI, and the percent change in CysC (%CysC) was calculated. The association of worsening renal function (WRF: %CysC ≥ 0) and baseline characteristics, including medications, was assessed. Results: Among 297 hypertensive patients with statins, 196 and 101 were with and without DM, respectively. Angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker, and β-blocker were prescribed in 56 (29%), 82 (42%), and 91 (46%) patients in the DM group, and 20 (20%), 52 (51%), and 52 (51%) in the non-DM group, respectively. The patients with WRF after PCI were 100 (51%) and 59 (58%) in the DM and non-DM groups (p = 0.261). Additionally, the %CysC had no significant differences between groups [median: 0%, interquartile range (IQR): -7.9% to 8.5% vs. median: 1.1%, IQR: -6.6% to 9.6%, p = 0.521]. Multivariate logistic analysis for WRF using relevant factors from univariate analysis showed that only β-blocker [odds ratio (OR): 2.76, 95% confidence interval (CI): 1.03–7.90, p = 0.048] was independently associated with WRF in the DM group whereas ACEI (OR: 0.07, 95% CI: 0.01–0.47, p = 0.012) was negatively correlated with WRF in the non-DM group. Conclusion: The β-blocker was the independent risk factor for WRF in patients with DM in the late phase after PCI for stable angina pectoris, while the use of ACEI had a renoprotective effect in patients without DM. [ABSTRACT FROM AUTHOR]

Background: Phenylacetylglutamine (PAGln)—a newly discovered microbial metabolite produced by phenylalanine metabolism—is reportedly associated with cardiovascular events via adrenergic receptors. Nonetheless, its association with cardiovascular outcomes in heart failure (HF) patients remains unknown. Objectives: This study aimed to prospectively investigate the prognostic value of PAGln for HF. Methods: Plasma PAGln levels were quantified by liquid chromatography‐tandem mass spectrometry. We first assessed the association between plasma PAGln levels and the incidence of adverse cardiovascular events in 3152 HF patients (including HF with preserved and reduced ejection fraction) over a median follow‐up period of 2 years. The primary endpoint was the composite of cardiovascular death or heart transplantation. We then assessed the prognostic role of PAGln in addition to the classic biomarker N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). The correlation between PAGln levels and β‐blocker use was also investigated. Results: In total, 520 cardiovascular deaths or heart transplantations occurred in the HF cohort. Elevated PAGln levels were independently associated with a higher risk of the primary endpoint in a dose‐response manner, regardless of HF subtype. Concurrent assessment of PAGln and NT‐proBNP levels enhanced risk stratification among HF patients. PAGln further showed prognostic value at low NT‐proBNP levels. Additionally, the interaction effects between PAGln and β‐blocker use were not significant. Conclusions: Plasma PAGln levels are an independent predictor of an increased risk of adverse cardiovascular events in HF. Our work could provide joint and complementary prognostic value to NT‐proBNP levels in HF patients. [ABSTRACT FROM AUTHOR]

Previous results regarding the association between types of β-blockers and outcomes in patients on hemodialysis (HD) were inconsistent. Our study aimed to evaluate patient survival according to the type of β-blockers administered using a large sample of patients with maintenance HD. Our study included patients on maintenance HD patients from a national HD quality assessment program (n = 54,132). We divided included patients into four groups based on their use and type; Group 1 included patients without a prescription of β-blockers, Group 2 included patients with a prescription of dialyzable and cardioselective β-blockers, Group 3 included patients with a prescription of non-dialyzable and non-cardioselective β-blockers, and Group 4 included patients with prescription of non-dialyzable and cardioselective β-blockers. The number of patients in Groups 1, 2, 3, and 4 were 34,514, 2789, 15,808, and 1021, respectively. The 5-year survival rates in Groups 1, 2, 3, and 4 were 69.3%, 66.0%, 68.8%, and 69.2%, respectively. Univariate Cox regression analyses showed the hazard ratios to be 1.10 (95% CI, 1.04–1.17) in Group 2 and 1.05 (95% CI, 1.02–1.09) in Group 3 compared to Group 1. However, multivariate Cox regression analyses did not show statistical significance among the four groups. Our study showed that there was no significant difference in patient survival based on the use or types of β-blockers. [ABSTRACT FROM AUTHOR]

Rational & objectiveBeta-blockers are recommended for patients with heart failure (HF) but their benefit in the dialysis population is uncertain. Beta-blockers are heterogeneous, including with respect to their removal by hemodialysis. We sought to evaluate whether β-blocker use and their dialyzability characteristics were associated with early mortality among patients with chronic kidney disease with HF who transitioned to dialysis.Study designRetrospective cohort study.Setting & participantsAdults patients with chronic kidney disease (aged≥18 years) and HF who initiated either hemodialysis or peritoneal dialysis during January 1, 2007, to June 30, 2016, within an integrated health system were included.ExposuresPatients were considered treated with β-blockers if they had a quantity of drug dispensed covering the dialysis transition date.OutcomesAll-cause mortality within 6 months and 1 year or hospitalization within 6 months after transition to maintenance dialysis.Analytical approachInverse probability of treatment weights using propensity scores was used to balance covariates between treatment groups. Cox proportional hazard analysis and logistic regression were used to investigate the association between β-blocker use and study outcomes.Results3,503 patients were included in the study. There were 2,115 (60.4%) patients using β-blockers at transition. Compared with nonusers, the HR for all-cause mortality within 6 months was 0.79 (95% CI, 0.65-0.94) among users of any β-blocker and 0.68 (95% CI, 0.53-0.88) among users of metoprolol at transition. There were no observed differences in all-cause or cardiovascular-related hospitalization.LimitationsThe observational nature of our study could not fully account for residual confounding.ConclusionsBeta-blockers were associated with a lower rate of mortality among incident hemodialysis patients with HF. Similar associations were not observed for hospitalizations within the first 6 months following transition to dialysis.

Abstract This retrospective study compared cardiovascular (CV) outcomes between initial β‐blocker (BB) + calcium channel blocker (CCB) dual therapy (“B + C”) and other initial dual therapies in Chinese newly diagnosed hypertensive patients. In this study, all patients in a regional electronic database with newly diagnosed hypertension from January 01, 2012 to December 31, 2016 who received any initial optimal dual therapy recommended by the Chinese hypertension guideline were included. 1:2 propensity score matching (PSM) was used to balance baseline characteristics between patients receiving B + C and patients receiving other initial dual therapies (“Others”). The primary outcome was major adverse cardiovascular events (MACE) that occurred from January 01, 2012 to December 31, 2017, consisting of non‐fatal stroke, non‐fatal myocardial infarction (MI), non‐fatal chronic heart failure (CHF), and all‐cause death. Cox proportional hazard models were used to compare these CV outcomes in the 2 matched cohorts. After the PSM, 6227 patients receiving B + C and 12 454 patients receiving Others were included. Compared to patients receiving Others, patients receiving B + C had a significantly lower risk of MACE (hazard ratio [HR] 0.85; 95% confidential interval [CI] 0.78–0.92; p

ObjectiveThis study aimed to assess whether β-blockers are associated with mortality in patients with sepsis.MethodWe conducted a retrospective cohort study of patients with sepsis using the Medical Information Market for Intensive Care (MIMIC)-IV and the emergency intensive care unit (eICU) databases. The primary outcome was the in-hospital mortality rate. The propensity score matching (PSM) method was adopted to reduce confounder bias. Subgroup and sensitivity analyses were performed to test the stability of the conclusions.ResultsWe included a total of 61,751 patients with sepsis, with an overall in-hospital mortality rate of 15.3% in MIMIC-IV and 13.6% in eICU. The inverse probability-weighting model showed that in-hospital mortality was significantly lower in the β-blockers group than in the non-β-blockers group [HR = 0.71, 95% CI: 0.66–0.75, p

We reported a patient with a fistula of the right coronary artery to the left ventricle, accompanied by dilation of the right coronary artery and persistent chest pain. This patient underwent surgical fistula closure surgery, but the fistula recurred. Persistent chest pain reappeared after encountering COVID-19 infection. We analyzed the mechanism of persistent myocardial ischemic chest pain caused by coronary artery fistula in this patient, the impact of surgery on the patient's disease, the possible mechanism of COVID-19 causing persistent ischemic chest pain in this patient, and the possible mechanism of metoprolol in alleviating myocardial ischemic chest pain in this patient.

Introduction Although septic shock mortality has decreased lately due to better identification and timely application of therapies. Research has continued for 20 years, but no therapies have been discovered yet to change sepsis's course once it is infected. Objective The aim of this study was to evaluate the effect of enteral metoprolol tartrate on hemodynamics and clinical outcomes in patients with septic shock grouped into various pretargeted heart rate (HR) groups. Methods Septic shock patients (n=90) were randomly assigned directly after the resuscitation into 3 groups (30 in each). Then, treatment with metoprolol tartrate was started. The dose of metoprolol was 25-150mg every 12 h and increased gradually to reach the pretargeted HR group range; group A (HR=60-70 beats/ min), group B (HR=71-80 beats/min), and group C (HR=81-90 beats/min). Metoprolol was continued to maintain the targeted HR till either discharge form intensive care unit (ICU) or death. The primary outcomes measured were mean arterial pressure (MAP), mixed venous oxygen saturation (SvO2), serum lactate, and sequential organ failure assessment (SOFA) score. Results After 1 day, group A (60-70 beats/min) had a significantly higher MAP (61.73±6.39 mmHg) than group B (51.33±7.76 mmHg) and group C (52.0±7.14 mmHg) (P < 0.001). After 3 days, group A had a significantly improved SvO2, lower serum lactate, and lower SOFA score than the other groups (all P < 0.05). When compared with groups B and C, group A had decreased norepinephrine (NE) requirements (P < 0.001) and shorter ICU stay (P=0.001). Conclusion Targeting HR between 60-70 beats/min using metoprolol tartrate, when compared with higher targets in septic shock after hemodynamic stabilization, was not associated with profound hypotension but also with earlier improved MAP, tissue perfusion measured as SvO2 and serum lactate, and organ failure measured as the SOFA score. It also showed decreased Norepinephrine requirements and a shorter ICU stay, but with no 28-day mortality benefit. [ABSTRACT FROM AUTHOR]

Melanoma is an aggressive skin cancer. Increasing evidence has shown the role of β-adrenergic receptors in the pathogenesis of melanoma. Carvedilol is a widely used non-selective β-AR antagonist with potential anticancer activity. The purpose of the study was to estimate the influence of carvedilol and sorafenib alone and in combination on the growth and inflammatory response of C32 and A2058 melanoma cells. Furthermore, this study also aimed to predict the probable interaction of carvedilol and sorafenib when administered together. Predictive study of the interaction of carvedilol and sorafenib was performed using the ChemDIS-Mixture system. Carvedilol and sorafenib alone and in combination showed a growth inhibitory effect on cells. The greatest synergistic antiproliferative effect on both cell lines was observed at Car 5 μM combined with Sor 5 μM. Analysis in silico identified diseases, proteins, and metabolic pathways that can be affected by the interaction of carvedilol and sorafenib. The results obtained demonstrated that carvedilol and sorafenib modulated the secretion of IL-8 by IL-1β-stimulated by melanoma cell lines but the use of a combination of both drugs did not intensify the effect. In summary, the results presented indicate that the combination of carvedilol and sorafenib may have a promising anticancer effect on melanoma cells. [ABSTRACT FROM AUTHOR]

The β-blocker carvedilol has been shown to prevent skin carcinogenesis in vitro and in vivo. Since systemic absorption of the β-blocker may cause cardiovascular disturbance, we developed a carvedilol loaded transfersome for skin-targeted delivery. Transfersomes were prepared using phospholipids and surfactants at various ratios and characterized. One formulation (F18) selected for further analysis was composed of carvedilol, soy phosphatidylcholine, and Tween-80 at a ratio of 1:3:0.5, which had a particle size of 115.6 ± 8.7 nm, a zeta potential of 11.34 ± 0.67 mV, and an encapsulation efficiency of 93.7 ± 5.1%. F18 inhibited EGF-induced neoplastic transformation of mouse epidermal JB6 P+ cells at non-toxic concentrations, while only high concentrations induced cytotoxicity in JB6 P+ and human keratinocytes HaCaT. Compared to the free drug, F18 released through the dialysis membrane and permeated through the porcine ear skin at a slower rate, but similarly depositing the drug in the epidermis and dermis of the skin. Consistently, surface application of F18 on reconstructed full-thickness human skin showed slower drug permeation, while it suppressed ultraviolet-induced DNA damage, inflammatory gene expression, and apoptosis. These data indicate that transfersome is a promising topical delivery system of carvedilol for preventing ultraviolet-induced skin damage and carcinogenesis.

This retrospective study compared cardiovascular (CV) outcomes between initial β‐blocker (BB) + calcium channel blocker (CCB) dual therapy ("B + C") and other initial dual therapies in Chinese newly diagnosed hypertensive patients. In this study, all patients in a regional electronic database with newly diagnosed hypertension from January 01, 2012 to December 31, 2016 who received any initial optimal dual therapy recommended by the Chinese hypertension guideline were included. 1:2 propensity score matching (PSM) was used to balance baseline characteristics between patients receiving B + C and patients receiving other initial dual therapies ("Others"). The primary outcome was major adverse cardiovascular events (MACE) that occurred from January 01, 2012 to December 31, 2017, consisting of non‐fatal stroke, non‐fatal myocardial infarction (MI), non‐fatal chronic heart failure (CHF), and all‐cause death. Cox proportional hazard models were used to compare these CV outcomes in the 2 matched cohorts. After the PSM, 6227 patients receiving B + C and 12 454 patients receiving Others were included. Compared to patients receiving Others, patients receiving B + C had a significantly lower risk of MACE (hazard ratio [HR] 0.85; 95% confidential interval [CI] 0.78–0.92; p <.001), non‐fatal stroke (HR 0.89; 95% CI 0.81–0.98; p =.018) and non‐fatal CHF (HR 0.74; 95% CI 0.63–0.86; p <.0001). Additionally, differences in risks of non‐fatal MI and all‐cause death between the 2 treatment cohorts were not statistically significant. In conclusion, BB + CCB initial dual therapy was associated with a lower risk of MACE, stroke, and CHF than other optimal initial dual therapies recommended by the Chinese hypertension guideline in Chinese newly diagnosed hypertensive patients. [ABSTRACT FROM AUTHOR]

Ivabradine is an established treatment for chronic heart failure with reduced ejection fraction (HFrEF); however, it is not used for acute heart failure treatment. Negative inotropic effects (NIE) often limit the up‐titration of β‐blockers. Contrarily, ivabradine has no NIE, and enables β‐blockers usage for treating patients with acute decompensated HFrEF. [ABSTRACT FROM AUTHOR]

β-blocker therapy is currently the treatment of choice for infantile hemangiomas (IH), albeit with limited data on long-term treatment outcomes. Herein, authors treated 67 IH lesions in 47 patients with oral propranolol at 2 mg/kg/d for a median of 9 mo and followed them up for a median of 48 mo. While no maintenance therapy was required for 18 lesions (26.9%), the rest needed maintenance therapy. Both treatment regimens had comparable efficacy (83.3±23.9% and 92.0±13.8%) but chances of IH recurrence was higher in lesions requiring maintenance therapy. Also, patients treated at ≤5 mo of age had a significantly better response and a lower recurrence rate than patients treated at >5 mo of age (95.0±7.9% vs. 87.0±17.5%, p = 0.05). Authors' experience suggests that longer durations of maintenance therapy offered no added advantage to the overall improvement of IH while treatment initiation at an earlier age showed better improvement and lower recurrence rates. [ABSTRACT FROM AUTHOR]

Abstract Ivabradine is an established treatment for chronic heart failure with reduced ejection fraction (HFrEF); however, it is not used for acute heart failure treatment. Negative inotropic effects (NIE) often limit the up‐titration of β‐blockers. Contrarily, ivabradine has no NIE, and enables β‐blockers usage for treating patients with acute decompensated HFrEF.

Simple Summary: Benzo(a)pyrene is a ubiquitously present environmental contaminant that induces lung cancer after being converted into active metabolites via aryl hydrocarbon receptor (AhR)-mediated metabolic activation. Previous reports showed that carvedilol is one of the most effective β-blockers with skin cancer preventive activity. The current study evaluated the effect and mechanism of carvedilol on benzo(a)pyrene-induced lung toxicity, inflammation and carcinogenesis. Carvedilol blocked the benzo(a)pyrene-induced malignant transformation of human bronchial epithelial cells and inhibited the benzo(a)pyrene-induced activation of the oncogenic signaling of ELK-1, NF-κB and AhR. This result suggests that the cross-talk of these signaling pathways plays an important role in mediating both inflammation and carcinogenesis in the lung. Carvedilol's activity was further confirmed on mouse models of acute lung toxicity and inflammation, as well as chronic lung cancer development induced by benzo(a)pyrene. As an FDA-approved generic drug, carvedilol may be repurposed as a lung cancer preventive agent. The current study evaluated the effects of the β-blocker carvedilol on benzo(a)pyrene (B(a)P) and its active metabolite benzo(a)pyrene diol epoxide (BPDE)-induced lung toxicity, inflammation and carcinogenesis and explored the potential mechanisms. Carvedilol blocked the BPDE-induced malignant transformation of human bronchial epithelial cells BEAS-2B. In BEAS-2B cells, B(a)P strongly activated ELK-1, a transcription factor regulating serum response element (SRE) signaling, which was attenuated by carvedilol. Carvedilol also inhibited the B(a)P-induced AhR/xenobiotic responsive element (XRE) and mRNA expression of CYP1A1 and attenuated B(a)P-induced NF-κB activation. In a B(a)P-induced acute lung toxicity model in CD-1/IGS mice, pretreatment with carvedilol for 7 days before B(a)P exposure effectively inhibited the B(a)P-induced plasma levels of lactate dehydrogenase and malondialdehyde, inflammatory cell infiltration and histopathologic abnormalities in the lung, and upregulated the expression of GADD45α, caspase-3 and COX-2 in the lung. In a B(a)P-induced lung carcinogenesis model in A/J mice, carvedilol treatment for 20 weeks did not affect body weight but significantly attenuated tumor multiplicity and volume. These data reveal a previously unexplored role of carvedilol in preventing B(a)P-induced lung inflammation and carcinogenesis by inhibiting the cross-talk of the oncogenic transcription factors ELK-1, AhR and NF-κB. [ABSTRACT FROM AUTHOR]

Background: Ulceration is an important complication in infantile hemangiomas (IHs). Prior to the use of β-blockers, the estimated incidence of this complication in a referral population was between 15% and 30%. The incidence and factors associated with ulceration have not been systematically studied since the emergence of β-blocker therapy.Objective: Examine the incidence and clinical predictors for ulceration in IHs.Methods: Retrospective study at tertiary referral centers.Results: Compared with a previous large pre-propranolol cohort study, ulceration occurred at a significantly lower incidence of 11.4%. Clinical factors associated with ulceration included partial segmental morphology, location in the diaper area, and size greater than 5 cm. Higher risk of ulceration in Black patients was observed, suggesting barriers to care including delayed diagnosis and referral to specialty care.Limitations: Retrospective design at tertiary referral centers.Conclusion: Compared with reports before the use of β-blockers became widespread, the incidence of ulceration in IHs has decreased. However, it continues to be a relatively frequent complication of IH. [ABSTRACT FROM AUTHOR]

Due to the inability of conventional wastewater treatment procedures to remove organic pharmaceutical pollutants, active pharmaceutical components remain in wastewater and even reach tap water. In terms of pharmaceutical pollutants, the scientific community focuses on β-blockers due to their extensive (over)usage and moderately high solubility. In this study, the photocatalytic activity of V2O5 was investigated through the degradation of nadolol (NAD), pindolol (PIN), metoprolol (MET), and their mixture under ultraviolet (UV) irradiation in water. For the preparation of V2O5, facile hydrothermal synthesis was used. The structural, morphological, and surface properties and purity of synthesized V2O5 powder were investigated by scanning electron microscopy (SEM), X-ray, and Raman spectroscopy. SEM micrographs showed hexagonal-shaped platelets with well-defined morphology of materials with diameters in the range of 10–65 µm and thickness of around a few microns. X-ray diffraction identified only one crystalline phase in the sample. The Raman scattering measurements taken on the catalyst confirmed the result of XRPD. Degradation kinetics were monitored by ultra-fast liquid chromatography with diode array detection. The results showed that in individual solutions, photocatalytic degradation of MET and NAD was relatively insignificant (<10%). However, in the PIN case, the degradation was significant (64%). In the mixture, the photodegradation efficiency of MET and NAD slightly increased (15% and 13%). Conversely, it reduced the PIN to the still satisfactory value of 40%. Computational analysis based on molecular and periodic density functional theory calculations was used to complement our experimental findings. Calculations of the average local ionization energy indicate that the PIN is the most reactive of all three considered molecules in terms of removing an electron from it. [ABSTRACT FROM AUTHOR]

While multi‐drug combinations and continuous treatment have become standard for multiple myeloma, the disease remains incurable. Repurposing drugs that are currently used for other indications could provide a novel approach to improve the therapeutic efficacy of standard multiple myeloma treatments. Here, we assessed the anti‐tumor effects of cardiac drugs called β‐blockers as a single agent and in combination with commonly used anti‐myeloma therapies. Expression of the β2‐adrenergic receptor correlated with poor survival outcomes in patients with multiple myeloma. Targeting the β2‐adrenergic receptor (β2AR) using either selective or non‐selective β‐blockers reduced multiple myeloma cell viability, and induced apoptosis and autophagy. Blockade of the β2AR modulated cancer cell metabolism by reducing the mitochondrial respiration as well as the glycolytic activity. These effects were not observed by blockade of β1‐adrenergic receptors. Combining β2AR blockade with the chemotherapy drug melphalan or the proteasome inhibitor bortezomib significantly increased apoptosis in multiple myeloma cells. These data identify the therapeutic potential of β2AR‐blockers as a complementary or additive approach in multiple myeloma treatment and support the future clinical evaluation of non‐selective β‐blockers in a randomized controlled trial. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Simple Summary: The most common heart disease in adult cats is hypertrophic cardiomyopathy (HCM), which is a slowly progressive, uncurable disease. Most cats with HCM live several years without obvious problems. However, several cats eventually develop life-threatening clinical signs or die suddenly. Hypertrophic cardiomyopathy is difficult to diagnose in clinically healthy cats because of the absence of any abnormalities on physical examination. However, several cats with HCM develop a heart murmur, which veterinarians can pick up at routine health checks. The reason for the murmur in many cats is an abnormal movement of a valve, which causes a leak and an obstruction. These findings can be visualized with cardiac ultrasonography. Noteworthy, the same ultrasonographic findings can be encountered in cats that do not have HCM but have an abnormality developed valve instead. An important difference between these two conditions is that some of the latter cases might be cured with life-long administration of a beta-blocker. The present study showed that the number of cats that benefited from atenolol therapy was disappointingly low. The reason why we examined only young cats with a heart murmur was that HCM occurs more frequently in elderly cats, whereas the potentially curable congenital disorder is present from birth. Background: Severe dynamic left ventricular outflow tract obstruction (DLVOTO) secondary to the systolic anterior motion of the septal mitral valve leaflet (SAM) can result either from congenital mitral valve disorders or left ventricular concentric hypertrophy of any cause, in cats commonly hypertrophic cardiomyopathy (HCM). Though HCM cannot be reversed, the question remains whether atenolol can cure cats with severe DLVOTO resulting from a presumed mitral valve dysplasia. Methods: In this retrospective case series, client-owned asymptomatic cats younger than 1.5 years with echocardiographic evidence of SAM and severe DLVOTO were included. Oral atenolol therapy and recheck echocardiography after 2–3 months were recommended. The owners and referring veterinarians were called for long-term follow-up information. Results: Of the 28 included cats, 23 were treated with atenolol. Recheck echocardiography performed in 17 cats showed a resolution of SAM in 47%. In the long term, SAM remained absent in only 9% of the treated cats. Cardiac-related death occurred in 26% of the atenolol-treated cats. Conclusions: The long term benefit of twice-daily atenolol therapy was documented in 9% of cats. Whether the cats where atenolol failed to resolve DLVOTO on long-term had HCM, or a therapy-resistant congenital primary mitral valve disorder remains unclear. [ABSTRACT FROM AUTHOR]

Background and Objectives: Previous studies have suggested that long-term β-blocker therapy before sepsis is associated with reduced mortality. Sepsis-associated coagulopathy (SAC) remains a common complication in patients with sepsis and is associated with increased mortality. Adrenergic pathways are involved in the regulation of the coagulation system. Pre-existing long-term β-blocker therapy may have potentially beneficial effects on SAC and has yet to be well characterized. We aimed to assess the potential association between pre-existing long-term β-blocker therapy and the outcomes of patients with SAC. Materials and Methods: This study retrospectively screened the clinical data of adult patients with SAC admitted to the Intensive Care Unit (ICU) and respiratory ICU between May 2020 and October 2022. Patients with SAC who took any β-blocker for at least one year were considered pre-existing long-term β-blocker therapy. All enrolled patients were followed up for 28 days or until death. Results: Among the 228 SAC patients, 48 received long-term β-blocker therapy before septic episodes. Pre-existing long-term β-blocker therapy was associated with reduced vasopressor requirements and a decreased 28-day mortality (log-rank test: p = 0.041). In particular, long-term β-blocker therapy was related to substantially lower D-dimer levels and a trend of improved activated partial thromboplastin time in patients with SAC during initial ICU admission. Multivariable regression analysis showed that long-term β-blocker therapy was significantly and independently associated with a 28-day mortality among patients with SAC (adjusted odds ratio, 0.55; 95% confidence interval, (0.32–0.94); p = 0.030). Conclusions: Pre-existing long-term β-blocker therapy might be associated with reduced vasopressor requirements and a decreased 28-day mortality among patients with SAC, providing evidence for the protective effect of β-blockers against SAC in managing sepsis. [ABSTRACT FROM AUTHOR]

β-blocker poisoning is frequently observed because of its primary use for the treatment of cardiovascular diseases. The management of β-blocker toxicity is dependent on the cardiovascular response and the severity of presentation. The present study describes the case of a patient with combined drug intoxication, β-blocker, digoxin, benzodiazepines, acetaminophen and opiates in a suicidal attempt. A 63-year-old female was found somnolent and in a confused state at her residence following intentional poly-drug ingestion. Upon presentation, she was found to be hemodynamically unstable and was thus treated with vasopressors. The toxicological screening performed upon presentation was positive for polydrug ingestion. On day 3, the patient developed chest pain and ST-segment elevation in anterior leads, while transthoracic echocardiographic assessment disclosed a non-dilated left ventricle with moderate dysfunction and akinesia of the apex. Coronary angiogram revealed normal coronary arteries and, subsequently, the diagnosis of Takotsubo cardiomyopathy (TTC) was suspected. Supportive treatment was initiated with favorable evolution and left ventricular ejection fraction normalization. The management of hemodynamic instability with vasopressors should be judiciously administered in the treatment of β-blocker poisoning, in view of the adverse effects on cardiac functions, including stress cardiomyopathy. [ABSTRACT FROM AUTHOR]

Purpose: To investigate ocular safety of intravitreal metoprolol in eyes with central serous chorioretinopathy. Methods: Five eyes of five patients diagnosed with chronic central serous chorioretinopathy (cCSC) previously treated unsuccessfully with oral spironolactone, micropulse laser and intravitreal anti‐vascular endothelial growth factor agents were enrolled and received off-label intravitreal metoprolol (50 µg/0.05 ml). Baseline and follow-up examinations included measurement of best-corrected visual acuity (BCVA), intraocular pressure, anterior chamber cellular/flare scores, vitritis classification, fluorescein and indocyanine green angiography, spectral domain optical coherence tomography and electroretinography (ERG), recorded by means of DTL electrodes and following the standard suggested by the International Society for Clinical Electrophysiology of Vision (ISCEV). The total follow-up period was 4 weeks. Results: There were no significant differences between baseline and follow-up ERG parameters: scotopic or photopic, a- and b-wave amplitude and implicit time, nor oscillatory potentials amplitude, or whatsoever. No intraocular inflammation sign was observed. In addition, BCVA showed small improvement in 4 or kept baseline values in 1 patient. The subretinal and/or intraretinal fluid volume reduced in all patients at 1 month after treatment. Conclusion: Patients with refractory cCSC treated with intravitreal 50 µg/0.05 ml metoprolol showed no signs of acute ocular toxicity, along with intraretinal fluid reduction and slight BCVA improvement 1 month after injection. This data suggest that intravitreal metoprolol may be a safe alternative for cCSC. [ABSTRACT FROM AUTHOR]

Previous results regarding the association between types of β-blockers and outcomes in patients on hemodialysis (HD) were inconsistent. Our study aimed to evaluate patient survival according to the type of β-blockers administered using a large sample of patients with maintenance HD. Our study included patients on maintenance HD patients from a national HD quality assessment program (n = 54,132). We divided included patients into four groups based on their use and type; Group 1 included patients without a prescription of β-blockers, Group 2 included patients with a prescription of dialyzable and cardioselective β-blockers, Group 3 included patients with a prescription of non-dialyzable and non-cardioselective β-blockers, and Group 4 included patients with prescription of non-dialyzable and cardioselective β-blockers. The number of patients in Groups 1, 2, 3, and 4 were 34,514, 2789, 15,808, and 1021, respectively. The 5-year survival rates in Groups 1, 2, 3, and 4 were 69.3%, 66.0%, 68.8%, and 69.2%, respectively. Univariate Cox regression analyses showed the hazard ratios to be 1.10 (95% CI, 1.04–1.17) in Group 2 and 1.05 (95% CI, 1.02–1.09) in Group 3 compared to Group 1. However, multivariate Cox regression analyses did not show statistical significance among the four groups. Our study showed that there was no significant difference in patient survival based on the use or types of β-blockers.