Use Of Β-blockers Research Articles

Factors associated with the severity of delirium.

Various factors affecting the development of delirium have been identified. However, the associations between the severity of delirium and potentially related factors have not been adequately investigated. The aim of the present study was to explore factors associated with the severity of delirium and to identify the reversible contributing factors. A total of 577 patients with delirium referred to the Department of Psychiatry during the 5 years from May 2015 to April 2020 at a general hospital were included. The Delirium Rating Scale-revised-98 (DRS-R-98) was used to measure the severity of delirium. Multiple regression analysis was used to determine whether individual factors were associated with the severity of delirium. Intensive care unit admission (p=0.003), use of benzodiazepines (p=0.01), dementia (p=0.02), and older age (p=0.045) were all positively associated the severity of delirium, while use of β-blockers (p=0.001) was negatively associated with the severity of delirium. Reversible contributing factors, that is use of benzodiazepines, should be avoided as much as possible, especially in elderly patients or patients with dementia or patients who need critical care in ICU. Reducing the dose of benzodiazepines or switching them to other drugs should be a priority.

Effect of β-blockers on the risk of COPD exacerbations according to indication of use: the Rotterdam Study.

Observational studies report a reduction of COPD exacerbations in patients treated with β-blockers. In contrast, the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK COPD) randomised controlled trial which excluded COPD patients with cardiovascular conditions showed an increase in COPD exacerbations. It is unclear whether this discrepancy could be explained by underlying cardiovascular comorbidity. We examined whether the association between use of β-blockers and risk of COPD exacerbations differed between patients with and without a cardiovascular indication for β-blockers use.Within the Rotterdam Study, we followed COPD subjects until the first COPD exacerbation, or end of follow-up. Cardiovascular indication for β-blockers use was defined as a history of hypertension, coronary heart disease, atrial fibrillation and/or heart failure at baseline. The association between β-blockers use and COPD exacerbations was assessed using Cox proportional hazards models adjusted for age, sex, smoking, incident cardiovascular disease (i.e. heart failure, hypertension, atrial fibrillation and/or coronary heart disease during follow-up), respiratory drugs and nitrates.In total, 1312 COPD patients with a mean age of 69.7±9.2 years were included. In patients with a cardiovascular indication (n=755, mean age of 70.4±8.8 years), current use of cardioselective β-blockers was significantly associated with a reduced risk of COPD exacerbations (HR 0.69, 95% CI 0.57–0.85). In contrast, in subjects without a cardiovascular indication (n=557, mean age of 68.8±9.7 years), current use of cardioselective β-blockers was not associated with an altered risk of COPD exacerbations (HR 0.94, 95% CI 0.55–1.62).Use of cardioselective β-blockers reduced the risk of exacerbations in COPD patients with concomitant cardiovascular disease. Therefore, the potential benefits of β-blockers might be confined to COPD patients with cardiovascular disease.

Prognostic benefits of prior amiodarone or β-blocker use before the onset of ventricular arrhythmia with hemodynamic collapse.

Although antiarrhythmic drugs have long been used for the suppression of various types of arrhythmias, their prior use before the onset of ventricular arrhythmia with hemodynamic collapse and the effect on prognosis is not well known. Data from 1004 consecutive patients with cardiovascular shock in the Japanese Circulation Society's Shock Registry were analyzed. Eighty-four cases of ventricular arrhythmia-induced shock and ROSC (return of spontaneous circulation) were divided into the prior amiodarone or β-blockers use group (Aβ group, n = 27) and the non-amiodarone and non-β-blockers use group (non-Aβ group; n = 57) based on treatment before the onset of those arrhythmias. Clinical outcomes related to hemodynamic collapse such as OHCA (out-of-hospital cardiovascular arrest) was less in the Aβ group [Aβ group, 11/26 (42%) vs. non-Aβ group, 41/56 (73%); p = 0.007]. Similarly, syncope was less common in the Aβ group than in the non-Aβ group [Aβ group 4/27 (15%) vs. non-Aβ group 27/57 (47%); p = 0.004]. Furthermore, prior amiodarone or β-blockers use before the onset of ventricular arrhythmias was strongly associated with both survival at discharge (odds ratio 3.19; 95% confidence interval 1.06-9.67; p = 0.040) and neurological outcomes at discharge (odds ratio 3.96; 95% confidence interval 1.32-11.85; p = 0.014) based on multivariate logistic regression analysis. Prior amiodarone or β-blockers use before the onset of malignant ventricular arrhythmia and maintaining appropriate blood concentrations in advance is associated with a good survival rate and better neurological outcomes after recovery from ventricular arrhythmia with hemodynamic collapse.

β-blocker use and risk of all-cause mortality in patients with coronary heart disease: effect modification by serum vitamin A.

Blockade of β-adrenoceptors reduces sympathetic nervous system activity and improves survival in patients with heart failure with reduced left ventricular ejection fraction (HFrEF); however, any improvement in longevity among patients with coronary heart disease (CHD) but without HFrEF remains uncertain. Vitamin A has been linked to the activation of tyrosine hydroxylase, the rate-limiting enzyme in the catecholamine synthesis pathway. We investigated if vitamin A status modified the association of β-blocker use with the risk of all-cause mortality. A total of 4118 patients undergoing elective coronary angiography for suspected stable angina pectoris, of whom the majority had normal left ventricular ejection fraction (LVEF) were studied. Hazard ratios (HRs) of all-cause mortality comparing treatment vs. non-treatment of β-blockers according to the tertiles of serum vitamin A were explored in Cox proportional hazards regression models. During a median follow-up of 10.3 years, 897 patients (21.8%) died. The overall LVEF was 65% and 283 (6.9%) had anamnestic HF. After multivariable adjustments for traditional risk factors, medical history, and drug therapies of cardiovascular disease, β-blocker treatment was inversely associated with the risk of all-cause mortality [HR : 0.84; 95% CI (confidence interval), 0.72-0.97]. However, the inverse association was generally stronger among patients in the upper serum vitamin A tertile (HR :0.66; 95% CI, 0.50-0.86; Pinteraction = 0.012), which remained present after excluding patients with LVEF < 40%. In patients with suspected CHD, β-blocker treatment was associated with improved survival primarily among patients with high serum vitamin A levels.

Association of Long-term Use of Antihypertensive Medications With Late Outcomes Among Patients With Aortic Dissection

The associations between long-term treatment of aortic dissection with various medications and late patient outcomes are poorly understood. To compare late outcomes after long-term use of β-blockers, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), or other antihypertensive medications (controls) among patients treated for aortic dissection. This population-based retrospective cohort study using the National Health Insurance Research Database in Taiwan included 6978 adult patients with a first-ever aortic dissection who survived to hospital discharge during the period between January 1, 2001, and December 31, 2013, and who received during the first 90 days after discharge a prescription for an ACEI, ARB, β-blocker, or at least 1 other antihypertensive medication. Data analysis was conducted from July 2019 to June 2020. Long-term use of β-blockers, ACEIs, or ARBs, with use of other antihypertensive medications as a control. The primary outcomes of interest were all-cause mortality, death due to aortic aneurism or dissection, later aortic operation, major adverse cardiac and cerebrovascular events, hospital readmission, and new-onset dialysis. Of 6978 total participants, 3492 received a β-blocker, 1729 received an ACEI or ARB, and 1757 received another antihypertension drug. Compared with patients in the other 2 groups, those in the β-blocker group were younger (mean [SD] age, 62.1 [13.9] years vs 68.7 [13.5] years for ACEIs or ARBs and 69.9 [13.8] years for controls) and comprised more male patients (2520 [72.2%] vs 1161 [67.1%] for ACEIs or ARBs and 1224 [69.7%] for controls). The prevalence of medicated hypertension was highest in the ACEI or ARB group (1039 patients [60.1%]), followed by the control group (896 patients [51.0%]), and was lowest in the β-blocker group (1577 patients [45.2%]). Patients who underwent surgery for type A aortic dissection were more likely to be prescribed β-blockers (1134 patients [32.5%]) than an ACEI or ARB (309 patients [17.9%]) or another antihypertension medication (376 patients [21.4%]). After adjusting for multiple propensity scores, there were no significant differences in any of the clinical characteristics among the 3 groups. No differences in the risks for all outcomes were observed between the ACEI or ARB and β-blocker groups. The risk of all-cause hospital readmission was significantly lower in the ACEI or ARB group (subdistribution hazard ratio [HR], 0.92; 95% CI, 0.84-0.997) and β-blocker group (subdistribution HR, 0.87; 95% CI, 0.81-0.94) than in the control group. Moreover, the risk of all-cause mortality was lower in the ACEI or ARB group (HR, 0.79; 95% CI, 0.71-0.89) and the β-blocker group (HR, 0.82; 95% CI, 0.73-0.91) than in the control group. In addition, the risk of all-cause mortality was lower in the ARB group than in the ACEI group (HR, 0.85; 95% CI, 0.76-0.95). The use of β-blockers, ACEIs, or ARBs was associated with benefits in the long-term treatment of aortic dissection.

Relation of Obstructive Sleep Apnea in Patients With a Coronary Chronic Total Occlusion to Coronary Collaterals and Mortality

A chronic total occlusion (CTO) is frequently identified in patients undergoing coronary angiography. The prognostic implications of intermittent hypoxia from obstructive sleep apnea (OSA) on patients with a CTO, and effects on collateral recruitment are unknown. The aim of this study was to determine the prevalence, vascular effects, and prognostic implications of the presence of OSA in patients with a CTO. Patients with a CTO between July 2010 and December 2019 were reviewed. Electronic medical records were accessed to determine documented patient history of OSA, demographics, and clinical course. Patients with robust collateral recruitment were defined as Rentrop grade 2 or 3. A total of 948 patients were included in the study, of which 127 (13.4%) had a documented history of OSA. These patients were younger (67.0 years vs 70.6 years, p < 0.01), had a higher body mass index (29.6 kg/m2 vs 26.7 kg/m2, p < 0.0001), higher rates of hypertension (91.3% vs 83.2%, p < 0.05), higher rates of smokers (63.3% vs 49.0%, p < 0.01) and more use of β-blockers (79% vs 68.5%, p < 0.05) and statins (92.7% vs 82.1%, p < 0.01). A documented history of OSA was independently associated with robust collaterals (OR 3.0 95%CI 1.5 to 5.8, p < 0.01) and lower mortality (HR 0.3 95% CI 0.1 to 0.7, p < 0.01) with a mean survival of 10.8 years, as compared to 8.1 years (log rank p < 0.0001). In conclusion, in patients with a CTO, documented OSA is independently associated with more robust coronary collaterals and lower mortality. The possible cardioprotective implications of intermittent hypoxia in OSA, as well as treatment effect requires further investigation.

Preprocedural β-Blockers in the Functional Assessment of Intermediate Coronary Lesions by Instantaneous Wave-Free Ratio.

Instantaneous wave-free ratio (iFR) has emerged as the strategy of choice for the assessment of intermediate coronary lesions. The impact of preprocedural β-blockers therapy on the iFR was the aim of this study. We included patients undergoing functional assessment of intermediate (40%-70%) coronary lesions in 2 centers. The iFR measurement was performed by pressure-recording guidewire and calculated at the core laboratory using the manufacturers' dedicated software. Minimal luminal diameter, reference diameter, percent diameter stenosis, and length of the lesion were measured. Positive iFR was considered for values <0.90. We included 197 patients undergoing functional evaluation of 223 coronary lesions. Patients on β-blockers (69%) had more frequently hypertension (P = .05); previous myocardial infarction (P = .01); therapy with clopidogrel (P = .02), statins, and aspirin; and acute coronary syndrome at presentation (P < .001, respectively). Mean iFR values were slightly higher in patients on β-blockers (0.94 ± 0.06 vs 0.92 ± 0.06, P = .11). The rate of positive iFR was significantly lower with β-blockers (14.9% vs 27.5%, P = .04). On multivariate analysis, β-blockers use was a predictor of the significance of coronary stenoses (odds ratio [OR] = 0.48; 95% CI = 0.23-0.98; P = .05) together with lesion length (OR = 1.04; 95% CI = 1.01-1.07; P = .007). Among patients undergoing iFR, preprocedural β-blockers are associated with higher absolute values and a lower rate of positive iFR.

Beta-blocker-associated hypoglycaemia: New insights from a real-world pharmacovigilance study.

To investigate the statistical association between hypoglycaemia and β-blocker use and to define what patient and drug characteristics could potentially increase the risk for its occurrence. We investigated the relationship between pharmacological parameters of β-blockers and the occurrence of hypoglycaemia by conducting a case/non case analysis using the Food and Drug Administration Adverse Event Reporting System database. Pharmacological properties that could represent a predictive factor for hypoglycaemia were analysed through a multilinear binary logistic regression (null hypothesis rejected for values of P < .05). We also performed a systematic review of clinical studies on this association. Of 83 954 selected reports, 1465 cases (1.75%) of hypoglycaemia were identified. The association was found statistically significant for nadolol (reporting odds ratio [95% confidence interval]: 6.98 [5.40-9.03]), celiprolol (2.35 [1.35-4.10]), propranolol (2.14 [1.87-2.46]) and bisoprolol (1.42 [1.25-1.61]). Paediatric cases (n = 310) showed a positive association with hypoglycaemia for long half-life drugs (odds ratio [95% confidence interval]: 2.232 [1.398-3.563]) and a negative association for β1-selectivity (0.644 [0.414-0.999]). Seven papers were included in the systematic review. Because of great heterogeneity in study design and demographics, hypoglycaemia incidence rates varied greatly among studies, occurring in 1.73% of the cases for propranolol treatment (n total participants = 575), 6.6% for atenolol (n = 30) and 10% for carvedilol (n = 20). Nadolol appears to be the β-blocker significantly most associated with hypoglycaemia and children represent the most susceptible sample. Furthermore, long half-life and nonselective β-blockers seem to increase the risk for its occurrence.

Therapeutic Controversies in the Medical Management of Valvular Heart Disease.

Objective:To evaluate the evidence for common therapeutic controversies in the medical management of valvular heart disease (VHD).Data Sources:A literature search of PubMed (inception to December 2020) was performed using the terms angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and aortic stenosis (AS); and adrenergic β-antagonists and aortic valve regurgitation (AR) or mitral stenosis (MS).Study Selection and Data Extraction:Randomized controlled trials (RCTs) and meta-analyses conducted in humans and published in English that reported ≥1 clinical outcome were included.Data Synthesis:Nine articles were included: 3 RCTs and 1 meta-analysis for ACE inhibitors/ARBs in AS, 1 RCT for β-blockers in AR, and 4 RCTs for β-blockers in MS. Evidence suggests that ACE inhibitors/ARBs do not increase the risk of adverse outcomes in patients with AS but may delay valve replacement. β-Blockers do not appear to worsen outcomes in patients with chronic AR and may improve left-ventricular function in patients with a reduced ejection fraction. β-Blockers do not improve and may actually worsen exercise tolerance in patients with MS in sinus rhythm.Relevance to Patient Care and Clinical Practice:ACE inhibitors/ARBs and β-blockers can likely be safely used in patients with AS or AR, respectively, who have a compelling indication. There is insufficient evidence to recommend routine use of β-blockers in patients with MS without atrial fibrillation.Conclusions:Common beliefs about the medical treatment of VHD are not supported by high-quality data. There remains a need for larger-scale RCTs in the medical management of VHD.

Orthostatic Hypertension and Hypotension and Outcomes in CKD: The CRIC (Chronic Renal Insufficiency Cohort) Study

Rationale & ObjectiveThere are limited data about the prevalence and prognostic significance of orthostatic hypo- and hypertension in patients with chronic kidney disease. The objective of this study is to determine the prevalence of orthostatic hypo- and hypertension in a cohort of patients with chronic kidney disease and examine their association with clinical outcomes.Study DesignProspective cohort study: Chronic Renal Insufficiency Cohort (CRIC) Study.Setting & Population7 clinical centers, participants with chronic kidney disease.ExposuresOrthostatic hypotension (decline in systolic blood pressure [BP] > 20 mm Hg) and orthostatic hypertension (increase in systolic BP > 20 mm Hg) from seated to standing position.OutcomesCardiovascular and kidney outcomes and mortality.Analytical ApproachLogistic regression was used to determine factors associated with orthostatic hypo- and hypertension; Cox regression was used to examine associations with clinical outcomes.ResultsMean age of study population (n = 3,873) was 58.1 ± 11.0 years. There was a wide distribution of change in systolic BP from seated to standing (from −73.3 to +60.0 mm Hg); 180 participants (4.6%) had orthostatic hypotension and 81 (2.1%) had orthostatic hypertension. Diabetes, reduced body mass index, and β-blocker use were independently associated with orthostatic hypotension. Black race and higher body mass index were independently associated with orthostatic hypertension. After a median follow-up of 7.9 years, orthostatic hypotension was independently associated with high risk for cardiovascular (HR, 1.12; 95% CI, 1.03-1.21) but not kidney outcomes or mortality. Orthostatic hypertension was independently associated with high risk for kidney (HR, 1.51; 96% CI, 1.14-1.97) but not cardiovascular outcomes or mortality.LimitationsOrthostatic change in BP was ascertained at a single visit.ConclusionsOrthostatic hypotension was independently associated with higher risk for cardiovascular outcomes, whereas orthostatic hypertension was associated with higher risk for kidney outcomes. These findings highlight the importance of orthostatic BP measurement in practice and the need for future investigation to understand the mechanisms and potential interventions to minimize the risk associated with orthostatic changes in BP.

Use of Calcium Channel Blockers and Risk of Active Tuberculosis Disease: A Population-Based Analysis.

Calcium channel blockers (CCBs) are known to reduce the availability of iron-an important mineral for intracellular pathogens. Nonetheless, whether the use of CCBs modifies the risk of active tuberculosis in the clinical setting remains unclear. To determine whether CCBs may modify the risk of active tuberculosis disease, we conducted a nested case-control study using the National Health Insurance Research Database of Taiwan between January 1999 and December 2011. Conditional logistic regression and disease risk score adjustment were used to calculate the risk of active tuberculosis disease associated with CCB use. Subgroup analyses investigated the effect of different types of CCBs and potential effect modification in different subpopulations. A total of 8164 new active tuberculosis cases and 816 400 controls were examined. Use of CCBs was associated with a 32% decrease in the risk of active tuberculosis (relative risk [RR], 0.68 [95% CI, 0.58-0.78]) after adjustment with disease risk score. Compared with nonuse of CCBs, the use of dihydropyridine CCBs was associated with a lower risk of tuberculosis (RR, 0.63 [95% CI, 0.53-0.79]) than nondihydropyridine CCBs (RR, 0.73 [95% CI, 0.57-0.94]). In contrast, use of β-blockers (RR, 0.99 [95% CI, 0.83-1.12]) or loop diuretics (RR, 0.88 [95% CI, 0.62-1.26]) was not associated with lower risk of tuberculosis. In subgroup analyses, the risk of tuberculosis associated with the use of CCBs was similar among patients with heart failure or cerebrovascular diseases. Our study confirms that use of dihydropyridine CCBs decreases the risk of active tuberculosis.

Seasonal fluctuation in intraocular pressure and its associated factors in primary open-angle glaucoma.

To evaluate seasonal fluctuations in intraocular pressure (IOP) in primary open-angle glaucoma (POAG) and its associated factors. POAG patients treated only with glaucoma eye drops were enroled. Winter and summer IOPs were evaluated. The Seasonal fluctuation rate of IOP was defined as follows: (mean winter IOP-mean summer IOP)/mean IOP in all seasons. Multiple linear regression analysis was used to explore factors associated with the seasonal IOP fluctuation rate including: age, gender, family history of glaucoma, type of glaucoma, number of eye drops, type of eye drops, mean deviation (MD) value, MD slope, disc haemorrhage, central corneal thickness and spherical equivalent. Winter IOP was higher than summer IOP in 204 POAG eyes of 204 patients, including 162 eyes with normal tension glaucoma (NTG) (13.2 ± 2.7 vs. 12.0 ± 2.3 mmHg, P < 0.001). The mean age and follow-up duration were 63.3 ± 11.4 years and 140.0 ± 66.9 months. Initial MD and MD slope were -2.1 ± 3.4 dB and -0.07 ± 0.50 dB/year, respectively. POAG was positively associated with the rate of seasonal IOP fluctuations compared to NTG (β = 5.29, P = 0.013). Family history, and timolol and carteolol use were also factors associated with the IOP fluctuation rate (β = -6.27, P = 0.007; β = 4.94, P = 0.030; and β = 4.51, P = 0.042, respectively). We confirmed seasonal IOP fluctuations in POAG. Type of glaucoma, family history of glaucoma, and β-blocker use might influence IOP fluctuations.

Increase use of β-blockers in patients with chronic obstructive pulmonary and cardiovascular disease.

Increase use of β-blockers in patients with chronic obstructive pulmonary and cardiovascular disease.

β-Blockers for traumatic brain injury: A systematic review and meta-analysis.

Paroxysmal sympathetic hyperactivity (PSH) and catecholamine surge, which are associated with poor outcome, may be triggered by traumatic brain injury (TBI).β Adrenergic receptor blockers (β-blockers), as potential therapeutic agents to prevent paroxysmal sympathetic hyperactivity and catecholamine surge, have been shown to improve survival after TBI. The principal aim of this study was to investigate the effect of β-blockers on outcomes in patients with TBI. For this systematic review and meta-analysis, we searched MEDLINE, EMBASE, and Cochrane Library databases from inception to September 25, 2020, for randomized controlled trials, nonrandomized controlled trials, and observational studies reporting the effect of β-blockers on the following outcomes after TBI: mortality, functional measures, and cardiopulmonary adverse effects of β-blockers (e.g., hypotension, bradycardia, and bronchospasm). With use of random-effects model, we calculated pooled estimates, confidence intervals (CIs), and odds ratios (ORs) of all outcomes. Fifteen studies with 12,721 patients were included. Exposure to β-blockers after TBI was associated with a significant reduction in adjusted in-hospital mortality (OR, 0.39; 95% CI, 0.30-0.51; I2 = 66.3%; p < 0.001). β-Blockers significantly improved the long-term (≥6 months) functional outcome (OR, 1.75; 95% CI, 1.09-2.80; I2 = 0%; p = 0.02). Statistically significant difference was not seen for cardiopulmonary adverse events (OR, 0.91; 95% CI, 0.55-1.50; I2 = 25.9%; p = 0.702). This meta-analysis demonstrated that administration of β-blockers after TBI was safe and effective. Administration of β-blockers may therefore be suggested in the TBI care. However, more high-quality trials are needed to investigate the use of β-blockers in the management of TBI. Systematic review and meta-analysis, level III.

Adrenergic Signaling in Immunotherapy of Cancer: Friend or Foe?

Simple SummaryExercise is associated with many aspects of a healthy lifestyle. Among these, exercise leads to the secretion of adrenaline and noradrenaline, which mobilize cells of the immune system, a process which is suggested to possess therapeutic value in cancer therapy, alone or in combination with immunotherapy. Strikingly, administration of β-blockers—which block the effect of adrenaline/noradrenaline—are also suggested to be useful in cancer therapy alone or in combination with immunotherapy. Herein we discuss the question of whether exercise and the administration of β-blockers could potentially be useful in cancer therapy.The incidence of cancer is increasing worldwide, which is to a large extent related to the population’s increasing lifespan. However, lifestyle changes in the Western world are causative as well. Exercise is intrinsically associated with what one could call a “healthy life”, and physical activity is associated with a lower risk of various types of cancer. Mouse models of exercise have shown therapeutic efficacy across numerous cancer models, at least in part due to the secretion of adrenaline, which mobilizes cells of the immune system, i.e., cytotoxic T and natural killer (NK) cells, through signaling of the β-2 adrenergic receptor (β2AR). Clinical trials aiming to investigate the clinical value of exercise are ongoing. Strikingly, however, the use of β-blockers—antagonists of the very same signaling pathway—also shows signs of clinical potential in cancer therapy. Cancer cells also express β-adrenergic receptors (βARs) and signaling of the receptor is oncogenic. Moreover, there are data to suggest that β2AR signaling in T cells renders the cell functionally suppressed. In this paper, we discuss these seemingly opposing mechanisms of cancer therapy—exercise, which leads to increased β2AR signaling, and β-blocker treatment, which antagonizes that same signaling—and suggest potential mechanisms and possibilities for their combination.

Effect of Ultrashort-Acting β-Blockers on Mortality in Patients With Sepsis With Persistent Tachycardia Despite Initial Resuscitation: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Historically, β-blockers have been considered to be relatively contraindicated for septic shock because they may cause cardiac suppression. On the other hand, there is an increasing interest in the use of β-blockers for treating patients with sepsis with persistent tachycardia despite initial resuscitation. Do ultrashort-acting β-blockers such as esmolol and landiolol improve mortality in patients with sepsis with persistent tachycardia despite initial resuscitation? This was a systematic review and meta-analysis. We searched MEDLINE, Cochrane Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) that compared the mortality of patients with sepsis and septic shock treated with esmolol or landiolol. We updated our search on April 20, 2020. Two independent reviewers assessed whether titles and abstracts met the following eligibility criteria: (1) RCT, (2) patients with sepsis and septic shock≥ 18 years of age, and (3) treatment with either esmolol/landiolol or placebo/no interventions. Two authors independently extracted selected patient and study characteristics and outcomes. The results of all analyses are presented using random effect models. Seven RCTs with a pooled sample size of 613 patients were included. Of these, six RCTs with 572 patients reported 28-day mortality. Esmolol or landiolol use in patients with sepsis and septic shock was significantly associated with lower 28-day mortality (risk ratio, 0.68; 95%CI, 0.54-0.85; P< .001). Unimportant heterogeneity was observed (I2= 31%). The absolute risk reduction and number of patients to be treated to prevent one death were 18.2%and 5.5, respectively. The use of ultrashort-acting β-blockers such as esmolol and landiolol in patients with sepsis with persistent tachycardia despite initial resuscitation was associated with significantly lower 28-day mortality. UMIN Clinical Trials Registry; No.: UMIN000040174; URL: https://www.umin.ac.jp/ctr/index.htm.

Treatment of Heart Failure with Mid-Range Ejection Fraction: What Is the Evidence.

In this review, we briefly outline our current knowledge on the epidemiology, outcomes, and pathophysiology of heart failure (HF) with mid-range ejection fraction (HFmrEF), and discuss in more depth the evidence on current treatment options for this group of patients. In most studies, the clinical background of patients with HFmrEF is intermediate between that of patients with HF and reduced ejection fraction (HFrEF) and patients with HF and preserved ejection fraction (HFpEF) in terms of demographics and comorbid conditions. However, the current evidence, stemming from observational studies and post hoc analyses of randomized controlled trials, suggests that patients with HFmrEF benefit from medications that target the neurohormonal axes, a pathophysiological behavior that resembles that of HFrEF. Use of β-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, and sacubitril/valsartan is reasonable in patients with HFmrEF, whereas evidence is currently scarce for other therapies. In clinical practice, patients with HFmrEF are treated more like HFrEF patients, potentially because of history of systolic dysfunction that has partially recovered. Assessment of left ventricular systolic function with contemporary noninvasive modalities, e.g., echocardiographic strain imaging, is promising for the selection of patients with HFmrEF who will benefit from neurohormonal antagonists and other HFrEF-targeted therapies.

The Total Antioxidant Status, Serum Selenium Concentrations and the Ultrasound Assessment Carotid Intima Media Thickness in Patients with Arterial Hypertension

The objective of the study was to establish the correlation between serum selenium concentrations, total antioxidant status, and the carotid intima media thickness in ultrasound assessment in patients with arterial hypertension. A group of 76 people suffering from arterial hypertension was qualified to participate in the study. The mean age of the respondents was 53.48 ± 12.78. Serum selenium concentrations (Se-S) and total antioxidant status (TAS) were determined in all respondents. Se-S were determined by hydride generation atomic absorption spectroscopy (HGAAS). The antioxidant status was assessed by the enzyme-linked immunosorbent assay (ELISA). In addition, an ultrasound exam of the carotid arteries was performed, and the intima media thickness (cIMT) was measured. In the study group, Se-S and TAS were 89.73 ± 18.99 µg/L and 1.18 ± 0.35 mM. However, the cIMT measured using ultrasound was 0.68 ± 0.15 mm. cIMT was significantly greater in patients with arterial hypertension with Se-S < median in comparison to patients with arterial hypertension with Se-S ≥ median (0.73 ± 0.19 mm vs. 0.65 ± 0.10 mm, p < 0.05), as well as in patients with arterial hypertension with TAS < median than in patients with arterial hypertension with TAS ≥ median (0.79 ± 0.18 mm vs. 0.56 ± 0.13 mm, p < 0.05). In regression analysis, older age, higher BMI, smoking, and lower serum selenium concentrations were independently correlated with the greater cIMT. Higher BMI and smoking were independent risk factors for the lower TAS, and the use of ACE inhibitors, β-blockers, and higher Se-S were independent factors of protection against the lower TAS. In patients with arterial hypertension, the lower total antioxidant status due to lower serum selenium concentrations may be correlated with an increase of the carotid intima media thickness measured using ultrasound.

Healthcare quality and mortality among patients hospitalized for heart failure by hospital level in Beijing, China.

AimsThis study sought to compare healthcare quality and 30 day, 90 day, and 1 year mortality rates among patients admitted to secondary and tertiary hospitals for heart failure (HF) in Beijing.Methods and resultsThis study retrospectively enrolled patients hospitalized with a primary discharge diagnosis of HF during January 2014 to December 2015, from five tertiary and four secondary hospitals, in Beijing, China. Mortality data were extracted from Beijing Death Surveillance Database. HF healthcare quality indices were used to evaluate in‐hospital care. Associations between hospital level and mortality rates were assessed using generalized linear mixed models, adjusting for patients' baseline characteristics and intra‐hospital correlation. Data from 1413 patients (median [interquartile range] age = 74 [65–80] years, 52.7% female) from secondary hospitals and 1250 patients (median [interquartile range] age = 72 [61–79] years, 43.3% female) from tertiary hospitals were collected. Rates of left ventricular ejection fraction assessment (73.2% vs. 90.1%) and combined use of β‐blockers and angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers (30.1% vs. 49.3%) were lower in secondary hospitals than those in tertiary hospitals, respectively. Patients admitted to secondary hospitals had a higher 90 day mortality [10.8% vs. 5.0%; adjusted odds ratio (OR): 2.06; 95% confidence interval (CI): 1.10–3.84, P = 0.024 and a higher 1 year mortality rate [21.0% vs. 12.1%; adjusted OR: 1.64; 95% CI: 1.02–2.62, P = 0.039], but 30 day mortality rates were not significantly different (5.5% vs. 3.0%; adjusted OR: 1.49; 95% CI: 0.63–3.52, P = 0.368).ConclusionsWorse quality of care for patients with HF in secondary hospitals was associated with higher 90 day and 1 year mortality rates. Improving care quality in secondary hospitals is crucial to improve prognosis of patients they served.

Dapagliflozin in the treatment of patients with heart failure with reduced left ventricular ejection fraction - a practical approach.

Because of its frequent occurrence, poor prognosis, low quality of life of patients accompanying the disease and high costs associated with treatment heart failure is a significant health problem in modern cardiology. The treatment of patients with heart failure and reduced ejection fraction (HFrEF) is supported by large-scale randomized clinical trials (RCTs), reflected in the ESC/HFA treatment recommendations. The use of β-blockers, inhibitors of the renin-angiotensin aldosterone system (RAA), including angiotensin converting enzyme ACE/ARB inhibitors, angiotensin and neprilysin receptor blockers (ARNI) and mineralocorticoid receptor antagonists (MRA) have been a solid basis for triple HFrEF therapy over the last few years, partially altering the natural history of patients with HF. Despite this, the 5-year survival rate in HF is still lower than for some types of cancer. Therefore, the search for new drugs to improve the prognosis of this disease is still ongoing. A new group of drugs – the so-called flozins, i.e. – is a great hope for a change in the natural history of heart failure. The following article presents practical aspects of using these drugs in the treatment of patients with HFrEF, taking into account both the inclusion criteria and various clinical profiles of patients.