Background Beta-blockers Research Articles

Effect of beta-blocker therapy on the response to mavacamten in patients with symptomatic obstructive hypertrophic cardiomyopathy.

In the EXPLORER-HCM trial, mavacamten improved exercise capacity and symptoms in patients with obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten effects on the primary endpoint, a composite of peak oxygen consumption (VO2 ) and New York Heart Association (NYHA) class, were greater in patients not receiving background beta-blockers than in those receiving beta-blockers. We sought to determine if the effect of background treatment was consistent across other clinically meaningful parameters. Subgroup analyses by beta-blocker use were performed in patients with oHCM from the EXPLORER-HCM and mavacamten long-term extension (MAVA-LTE) studies. In EXPLORER-HCM, 189 patients (75.3%) were receiving beta-blockers, and 62 (24.7%) were receiving non-dihydropyridine calcium channel blockers or no background HCM medication; 170 patients (90.4%) receiving beta-blockers had chronotropic incompetence. Improvements in peak VO2 at week 30 with mavacamten versus placebo were lower with beta-blockers (mean difference [95% confidence interval (CI)]: 1.04 [0.12, 1.95] ml/kg/min) than without beta-blockers (mean difference [95% CI]: 2.69 [1.29, 4.09] ml/kg/min); improvements in non-heart rate-dependent parameters (VE /VCO2 slope) appeared unaffected by beta-blockers. Improvements in functional capacity parameters at week 30 with mavacamten versus placebo were independent of beta-blockade for post-exercise left ventricular outflow tract gradient (mean difference [95% CI]: -37.9 [-48.0, -27.9] mmHg with beta-blockers; -33.5 [-53.6, -13.3] mmHg without beta-blockers), proportion of patients with reduction of ≥1 NYHA class, Kansas City Cardiomyopathy Questionnaire clinical summary scores and N-terminal pro-B-type natriuretic peptide. Mavacamten benefits were reproduced and maintained in MAVA-LTE regardless of beta-blockade. Mavacamten improved measures of functional capacity, left ventricular outflow tract obstruction, symptom burden and biomarkers in patients with HCM regardless of beta-blocker use. Beta-blocker use was often associated with chronotropic incompetence, affecting peak VO2 and other heart rate-dependent measures, but had minimal impact on heart rate-independent measures.

Betablockers reduce oxygen pulse increase and performance in heart failure patients with preserved ejection fraction

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

THE EFFECT OF BETA BLOCKAGE IN PATIENTS FOLLOWING ACUTE CORONARY SYNDROME - STRATIFIED ACCORDING TO LEFT VENTRICULAR EJECTION FRACTION.

THE EFFECT OF BETA BLOCKAGE IN PATIENTS FOLLOWING ACUTE CORONARY SYNDROME - STRATIFIED ACCORDING TO LEFT VENTRICULAR EJECTION FRACTION.

Betablockers and Ivabradine Titration According to Exercise Test in LV Only Fusion CRT Pacing.

Background: Betablockers (BB)/ivabradine titration in fusion CRT pacing (CRTP) is understudied. Aim: To assess drug optimization using systematic exercise tests (ET) in fusion CRTP with preserved atrioventricular conduction (AVc). Methods: Changes in drug management were assessed during systematic follow-ups in CRTP patients without right ventricle lead. Shorter AVc (PR interval) allowed BB up-titration, while longer AVc needed BB down-titration, favoring ivabradine. Constant fusion pacing was the goal to improve outcomes. Results: 64 patients, 62.5 ± 9.5 y.o divided into three groups: shorter PR (<160 ms), normal (160–200 ms), longer (200–240 ms); follow-up 59 ± 26 months. Drugs were titrated in case of: capture loss due to AVc shortening (14%), AVc lengthening (5%), chronotropic incompetence (11%), maximum tracking rate issues (9%), brady/tachyarrhythmias (8%). Interventions: BB up-titration (78% shorter PR, 19% normal PR, 5% longer PR), BB down-titration (22% shorter PR, 14% normal PR), BB exclusion (16% longer PR), adding/up-titration ivabradine (22% shorter PR, 19% normal PR, 5% longer PR), ivabradine down-titration (22% shorter PR, 3% normal PR), ivabradine exclusion (11% normal PR, 5% longer PR). Drug strategy was changed in 165 follow-ups from 371 recorded (42% patients). Conclusions: BBs/ivabradine titration and routine ET during follow-ups in patients with fusion CRTP should be a standard approach to maximize resynchronization response. Fusion CRTP showed a positive outcome with important LV reverse remodeling and significant LVEF improvement in carefully selected patients.

Polygenic Score For Beta-blocker Survival Benefit In Heart Failure With Preserved Ejection Fraction Patients

Background Beta-blockers (BB) are mainstay therapy for heart failure with reduced ejection fraction (HFrEF), but are not proven helpful for HF with preserved EF (HFpEF). We recently defined a genomic profile for enhanced BB survival benefit in HFrEF (Polygenic Response Predictor; PRP) and sought to test whether this could define a favorable responder group among HFpEF patients. Methods Patients with HF and EF ≥50% of European descent (n=450, deaths=132) from two studies (the Henry Ford Pharmacogenomic Registry (HFPGR); n=338 and TIME-CHF; n=112) were included. The PRP was used to categorize patients into predicted responders vs. predicted non-responders as previously described. This was tested in Cox models predicting time to all-cause mortality, adjusted for clinical risk score (MAGGIC), level of BB-exposure, PRP category and BB-exposure*PRP-category interaction, with meta-analysis then used to pool overall study results. Results Greater BB exposure trended toward reduced all-cause mortality in HFpEF patients in PRP predicted responder group (n=103; HR=0.39 [95% CI=0.097-1.56], p=0.18), and toward hazard among PRP predicted non-responders (n=347; HR=1.38 [95% CI=0.67-2.8], p=0.38), an interaction that was near significant (p interaction =0.11). The figure shows forest plot of BB HR in each PRP category for each study cohort and overall. Conclusions Among patients of European ancestry with HFpEF, the BB PRP may be able to differentiate BB responders from those that derive hazard from BB exposure. Additional testing is needed in larger HFpEF cohorts. Beta-blockers (BB) are mainstay therapy for heart failure with reduced ejection fraction (HFrEF), but are not proven helpful for HF with preserved EF (HFpEF). We recently defined a genomic profile for enhanced BB survival benefit in HFrEF (Polygenic Response Predictor; PRP) and sought to test whether this could define a favorable responder group among HFpEF patients. Patients with HF and EF ≥50% of European descent (n=450, deaths=132) from two studies (the Henry Ford Pharmacogenomic Registry (HFPGR); n=338 and TIME-CHF; n=112) were included. The PRP was used to categorize patients into predicted responders vs. predicted non-responders as previously described. This was tested in Cox models predicting time to all-cause mortality, adjusted for clinical risk score (MAGGIC), level of BB-exposure, PRP category and BB-exposure*PRP-category interaction, with meta-analysis then used to pool overall study results. Greater BB exposure trended toward reduced all-cause mortality in HFpEF patients in PRP predicted responder group (n=103; HR=0.39 [95% CI=0.097-1.56], p=0.18), and toward hazard among PRP predicted non-responders (n=347; HR=1.38 [95% CI=0.67-2.8], p=0.38), an interaction that was near significant (p interaction =0.11). The figure shows forest plot of BB HR in each PRP category for each study cohort and overall. Among patients of European ancestry with HFpEF, the BB PRP may be able to differentiate BB responders from those that derive hazard from BB exposure. Additional testing is needed in larger HFpEF cohorts.

Abstract 10129: Long-Term Prescription of Beta-Blockers After Myocardial Infarction with Preserved Left Ventricular Function is Associated with Reduction in Recurrent ACS but Not Repeat Revascularization or All-Cause Mortality

Background: Beta-blockers (BB) are cornerstones of medical therapy for acute coronary syndromes (ACS). However, benefits of long-term treatment with preserved left ventricular ejection fraction (LVEF) are not well established. We examined whether long-term BB prescription is associated with risks of recurrent ischemic events or all-cause mortality in patients with LVEF&gt;50% after ACS. Methods: We conducted a retrospective observational study in Alberta, Canada by linking data from provincial databases (APPROACH, echo, discharge and pharmacy). We included patients with NSTEMI or STEMI between 2008-2017, in-hospital LVEF≥50%, who survived ≥180 days after index discharge and had a new prescription for a BB post ACS. We used adjusted Cox proportional hazards models to determine the association between duration of BB therapy (dichotomized at 180 days) and the primary composite outcome of recurrent ACS, repeat revascularization or all-cause mortality ≥180 days after index ACS. Secondary outcomes were the components of the composite. Results: Of 4,768 included patients (mean age 62.0y, 28.1% female), 1155 (24.2%) discontinued BB before 180 days. During a median follow up time of 56.6 months, 964 patients (20.2%) had a primary outcome event. In the overall population, early BB discontinuation was not associated with an increased risk of the primary outcome (adjusted HR 1.13, 95% CI:0.99-1.29 p=0.07) but was associated with the secondary outcome of recurrent ACS (HR 1.43; 95% CI: 1.164-1.756, p&lt;0.001). In the subgroup with STEMI (n=2,428) early BB discontinuation was associated with increased risk of the primary outcome (HR 1.27; 95% CI: 1.054-1.524, p=0.01), again driven by recurrent ACS. Early BB discontinuation was not associated with secondary outcomes of receipt of repeat revascularization or all-cause mortality. Conclusion: In patients discharged after ACS with preserved LVEF, continuation of BB beyond 180 days was not associated with a reduced risk of the composite primary outcome overall, though subgroup analysis suggested a benefit in the subgroup with STEMI, and in the secondary outcome of recurrent ACS. Large-scale randomized trials are required to clarify the appropriate duration of BB therapy after ACS in patients with preserved LVEF.

The impact of regular bisoprolol on the response to salbutamol in asthma: A double‐blind randomized placebo‐controlled crossover trial

Non-selective beta-blockers impair the bronchodilator response to beta2 -agonists. Cardio-selective beta1 -blockers are less likely to cause this effect, yet they remain relatively contraindicated in asthma. We investigated whether the response to salbutamol is impaired during cardio-selective beta1 -blocker treatment in people with asthma. A random-order, double-blind, placebo-controlled, non-inferiority, crossover study was conducted comparing up to 5 mg bisoprolol daily for 2 weeks with matching placebo, with an open-label extension of up to 10 mg bisoprolol daily. After each treatment period, mannitol was inhaled to induce bronchoconstriction with a 15% fall in forced expiratory volume in 1 s (FEV1 ). Immediately after mannitol challenge, salbutamol (100, 100 and 200 μg) was administered via spacer at 5-min intervals with repeated FEV1 measures. The FEV1 recovery with salbutamol was measured as an area under recovery curve (AUC). Based on earlier research, a clinically relevant non-inferiority limit of a 30% reduction in the AUC was set. A total of 19 adults with mild asthma and positive inhaled mannitol challenge completed the study. Adjusting for the FEV1 fall induced by mannitol and treatment sequence, the mean AUC response to salbutamol after bisoprolol was 5% lower than after placebo, with a one-sided 95% confidence interval (CI) of 26% lower. Thirteen participants completed the open-label extension up to 10 mg bisoprolol daily with mean AUC 11% higher after bisoprolol with a 95% CI of 5% lower. The bronchodilator response to rescue salbutamol after mannitol-induced bronchoconstriction is non-inferior during regular treatment with the cardio-selective beta1 -blocker, bisoprolol, compared to placebo. ACTRN12618000306213 at https://www.anzctr.org.au.

The Impact of Beta Blockers on Survival Outcomes in Patients With Non–small-cell Lung Cancer Treated With Immune Checkpoint Inhibitors

BackgroundBeta blockers have been associated with anti-tumorigenic effects, potentially by reducing adrenergic-mediated stress responses. Preclinical studies have additionally shown that beta blockade may enhance the efficacy of cancer immunotherapy. We investigated patients with lung cancer who concomitantly used beta blockers and immune checkpoint inhibitors (ICIs), with the hypothesis that beta blockade would positively impact clinical outcomes. Patients and MethodsWe retrospectively reviewed the health records of 109 patients who were treated at Northwestern University from January 2014 through August 2018 with ICIs for non–small-cell lung cancer (NSCLC). Comparisons of overall survival and progression-free survival (PFS) were performed using Kaplan-Meier analysis with log-rank test, and a univariate regression analysis was performed with a Cox proportional hazards model. ResultsAmong 109 patients treated with ICIs for NSCLC, 28 of them were concomitantly prescribed beta blockers. Use of beta blockers was associated with increased PFS, with a hazard ratio of 0.58 and 95% confidence interval of 0.36 to 0.93. There was not a significant increase in overall survival among patients who took beta blockers (hazard ratio, 0.66; 95% confidence interval, 0.38-1.17). In a regression model, beta blockers were identified as predictive of PFS, as were non-squamous histology, tumor programmed death-ligand 1 positivity, and lower line of treatment. ConclusionsOur data suggests beta blocker use may be associated with improved PFS among patients treated with ICIs for NSCLC. This was a small study, and these findings should be further validated in prospective clinical studies.

Practice Variation in Establishing the Adequacy of Beta-Blockers as an Antiarrhythmic Agent in School-Aged Children and Adolescents

BackgroundBeta-blockers (BBs) are commonly prescribed to manage arrhythmias in children and adolescents without any standardised approach to establish BB adequacy. We invited all Canadian pediatric cardiologists to participate in an anonymous survey to understand practice variation in the assessment of BB adequacy in school-aged children and adolescents with arrhythmia or the potential for arrhythmia. MethodsAn electronic survey approved by the Institutional Ethics Board was distributed by e-mail to 96 Canadian pediatric cardiologists who had been active in practice for at least 1 year. Incomplete surveys were excluded. ResultsForty-one cardiologists (43%) responded to all questions in the survey. Thirteen cardiologists (32%) reported always assessing BB adequacy, 17 (41%) did so only for specific arrhythmias, and 11 (27%) reported never performing such an assessment. A total of 19 cardiologists (46%) and 18 cardiologists (44%) reported using Holter monitoring and exercise testing, respectively, to assess beta receptor blockade adequacy. Thirteen cardiologists (32%) considered BB therapy adequate if Holter demonstrated a 20% decrease in heart rate (HR) from baseline, and 10 respondents (24%) defined adequate BB therapy using exercise testing as a 20% decrease in maximal HR or blood pressure from baseline. ConclusionDespite wide variation in practice, Holter monitoring and exercise testing are commonly used methods to measure the adequacy of BB therapy. There are no standard criteria, but the majority (56%) reported using a 20% decrease in HR or blood pressure from the pretreatment state as a criterion for adequate BB therapy in children and adolescents with arrhythmia or the potential for arrhythmia.

The effect of beta-blockers on mortality in patients with heart failure and atrial fibrillation: A meta-analysis of observational cohort and randomized controlled studies

Beta-blockers (BB) are the cornerstone of therapy for heart failure (HF); however, the effects of these drugs on the prognosis of patients with concomitant atrial fibrillation (AF) remain controversial. The objective of this meta-analysis was to evaluate the efficacy of BB on mortality in HF coexisting with AF. A systematic search of PubMed, Embase and the Cochrane Library databases was conducted. Observational cohort studies and randomized controlled trials reporting outcomes of mortality or HF hospitalizations for patients with HF and AF, being assigned to BB treatment. A non-BB group was also included. A total of 8 clinical studies (5 randomized controlled trials and 3 observational cohort studies) involving 34197 patients were included in the analysis. The pooled analysis demonstrated that BB treatment was associated with a 22% reduction in relative risk of all-cause mortality in patients with HF and AF (RR: 0.78; 95% CI 0.71-0.86; p < 0.00001; I2 = 27%). The pooled analysis of 5 studies reported the outcome of HF hospitalization (2774 patients) which showed that BB therapy was not associated with a reduction of HF hospitalizations (RR: 0.94; 95% CI 0.79-1.11; p = 0.46; I2 = 38%). Meta-analysis suggests the potential mortality benefit of BB in patients with HF and AF. It was concluded herein that it is premature to deny patients with AF and HF to receive BB therapy considering current evidence.

A Polygenic Response Predictor Indicates Survival Benefit of Beta-Blockade in Heart Failure Patients

Background Beta-blockers (BB) are one of the most important therapeutic options for heart failure (HF). However, individual responses to BB treatment vary, which may be due, in part, to genetic variation. We sought to use an unbiased approach to look for a multi-genetic marker profile of BB effectiveness. No previous studies, to our knowledge, have provided insights about treatment-specific survival prediction by combining multiple genetic markers using a genome-wide (GW) approach. Method Two studies were utilized; Henry Ford Pharmacogenomic Registry (HFPGR) and TIME-CHF. HFPGR patients who were of European ancestry (N=496), met Framingham criteria for HF and had a history of ejection fraction (EF) Results After imputation and quality control, 7,055,710 SNPs, were available for analysis. Over a median follow up of 2.0 years there were 53 deaths in derivation, 36 in HFPGR validation and 165 in TIME. The optimized model identified 44 SNPs to make up the PRP with optimal cutoff at the 30th percentile (≤30% are BB responders and >30% are BB non-responsive). The results are shown in the figure. In the HFPGR validation set the HR of BB exposure for death in the BB responders vs. non-responders were 0.02 vs. 1.07 (p-value for interaction=0.208), while in TIME-CHF these were 0.12 vs. 0.98 (p-value for interaction=0.029). Conclusion A BB-PRP among European ancestry patients (a 44-SNP genetic profile) replicated in two distinct cohorts and may identify patient subgroups that are BB responders vs. non-responders. Additional study is needed to prospectively validate this BB-PRP, illuminate the mechanisms underlying the PRP, and establish similar tools in other ancestral groups (e.g. African Americans).

Effectiveness of beta-blockers depending on the genotype of congenital long-QT syndrome: A meta-analysis.

BackgroundBeta-blockers are first-line therapy in patients with congenital long-QT syndrome (LQTS).ObjectiveThis study sought to determine the differences in effectiveness of beta-blockers on risk reduction according to LQTS genotype.MethodsWe searched MEDLINE, EMBASE, and CENTRAL databases to investigate the use of beta-blockers (atenolol, nadolol, propranolol, and metoprolol) in patients with LQTS. Hazard ratio (HR) and relative risk (RR) were extracted or calculated from studies reporting cardiac events (syncope, aborted cardiac arrest (ACA), or sudden cardiac death (SCD)).ResultsAmong 2,113 articles searched, 10 studies (7 registry-based cohort studies (Cohort) and 3 interrupted time series studies (ITS)) involving 9,727 patients were included. In a meta-analysis using a random-effect model, the use of beta-blocker was associated with significant risk reduction of all cardiac events (HR 0.49, p<0.001 in Cohort; RR 0.39, p<0.001 in ITS) and serious cardiac events (ACA or SCD) (HR 0.47, p<0.001 in Cohort). In both LQT1 and LQT2, the risk was reduced with beta-blocker therapy in Cohort (HR 0.59 in LQT1; HR 0.39 in LQT2) as well as ITS (RR 0.29 in LQT1; RR 0.48 in LQT2). Among the beta-blockers, nadolol showed a significant risk reduction in both LQT1 and LQT2 (HR 0.47 and 0.27, respectively), whereas atenolol and propranolol decreased the risk only in LQT1 (HR 0.36 and 0.46, respectively). Metoprolol showed no significant reduction in either genotype. In LQT3, beta-blocker therapy was not as effective as LQT1 or LQT2; however, it was inconclusive due to data insufficiency.ConclusionThis meta-analysis showed that beta-blockers were effective in reducing risk of cardiac events in patients with LQTS. Among them, nadolol was effective in LQT1 and LQT2, whereas other drugs showed different effectiveness depending on LQT genotype.

The Treatment Effect of an ACE-Inhibitor Based Regimen with Perindopril in Relation to Beta-Blocker use in 29,463 Patients with Vascular Disease: a Combined Analysis of Individual Data of ADVANCE, EUROPA and PROGRESS Trials

IntroductionIn everyday practice, angiotensin converting enzyme inhibitors and beta-blockers are cornerstone treatments in patients with (cardio-)vascular disease. Clear data that evaluate the effects of the combination of these agents on morbidity and mortality are lacking.MethodsIn this retrospective pooled analysis of three large perindopril outcome trials (ADVANCE, EUROPA, PROGRESS), clinical outcomes were evaluated in 29,463 patients with vascular disease. Multivariate Cox regression analyses were performed in patients randomized to a perindopril-based regimen or placebo (treatment effect), and data were stratified according to background beta-blocker treatment. The primary endpoint was a composite of cardiovascular mortality, non-fatal myocardial infarction, and stroke.ResultsThe cumulative incidence of the primary endpoint over mean follow-up of 4.0 years (Sd 1.0) was significantly lower in the beta-blocker/perindopril group (9.6%; 545/5700 patients) as compared to beta-blocker/placebo (11.8%; 676/5718 patients) (p < 0.01). Adding perindopril to existing beta-blocker treatment reduced the relative risk of the primary endpoint by 20% (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.71–0.90), non-fatal myocardial infarction by 23% (HR 0.77; 95% CI 0.65–0.91), and all-cause mortality by 22% (HR 0.78; 95% CI 0.68–0.88) as compared to placebo. Significant treatment benefit was not observed for stroke (HR 0.93; 95% CI 0.75–1.15). Significance was maintained for the primary endpoint and cardiovascular endpoints when data were further stratified by baseline hypertension. However, the mortality benefit was only observed in patients with hypertension with background beta-blocker use.ConclusionsThese data suggest that the beneficial cardioprotective effects of perindopril treatment are additive to the background beta-blockers use.

Prior beta blockers use is independently associated with increased inpatient mortality in patients presenting with acute myocardial infarction

BackgroundBeta blockers (BBs) are recommended for patients presenting with acute myocardial infarction. However, the effects of prior BBs use on inpatient mortality in patients presenting with acute myocardial infarction (AMI) are unknown. MethodsThis was a retrospective cohort study of patients presenting with AMI in Florida Hospital Orlando from January 1, 2013 to December 31, 2014. Data were collected prospectively, as part of the Acute Coronary Treatment and Intervention Outcomes Network (ACTION) Registry. Results1128 patients were included in the analysis, with 354 (31.4%) patients on home BBs and 774 (68.6%) not on home BBs on presentation. Patients in prior BBs group were older, had higher incidence of multiple comorbidities, and were more likely to take cardiovascular medications. During hospitalization, Patients in prior BBs group were more likely to develop decompensated heart failure (9.9% vs. 3.6%, P<0.001), less likely to have STEMI (33.9% vs. 54.4%, P<0.001), and subsequently less PCI (73.2% vs. 81.3%, P=0.002), but higher inpatient mortality (8.8% vs. 4.8%, P=0.009). In multivariable logistic regression analysis, prior BBs use was independently associated with increased inpatient mortality (adjusted OR 3.15, 95% CI 1.44-6.87, P=0.004), as well as in GRACE model (adjusted ratio=1.83, 95% CI 1.01-3.34, P<0.047). However, prior BBs use did not contribute significantly to predict inpatient mortality on the basis of GRACE model in terms of discrimination and calibration. ConclusionsPrior BBs use was independently associated with increased inpatient mortality, and should be considered a high risk marker for patients presenting with acute myocardial infarction.

The role of physicians' knowledge of guidelines in the usage of beta-blockers in heart failure

Background: Beta-blockers (BB) are recommended in the management of heart failure (HF), but its usage has been reported as low. The role of physicians' knowledge of guidelines in this observation has not been fully investigated. Objectives: The objective was to determine whether a gap in the physicians' knowledge of guidelines for the use of BB in HF is a reason for its low usage. Materials and Methods: Questionnaires were distributed to physicians in the Departments of Internal and Family Medicine. Multiple choice questions based on the 2016 European Society of Cardiology guidelines for the use of BB in HF were in the questionnaire. A physician was adjudged knowledgeable of the guidelines if he/she scored 50% or above. The proportion of physicians with inadequate knowledge was derived as a percentage of all respondents. Chi-square test was used to determine whether department, gender and cadre were associated with knowledge of guidelines. Results: A total of 70 physicians responded. Departments of Family and Internal Medicine, respectively. Fifty-five (78.6%) of them were not knowledgeable about the guidelines for the use of BB in HF, while only 15 (21.4%) were knowledgeable. Association between a physician's department, gender, cadre and knowledge of HF guidelines yielded P = 0.774, 0.144 and 0.227, respectively. Conclusion: There is a gap in the physicians' knowledge of the guidelines for BB use in HF. Measures to educate and regularly update physicians on HF guidelines should be institutionalised to ensure evidence-based practice, improved care and better outcomes.

Relationship between different doses of beta-blockers and prognosis in elderly patients with reduced ejection fraction

BackgroundBeta-blockers (BBs) remain underused in elderly patients with reduced ejection fraction (REF). Our aim was to determine the prognostic impact of different doses of BB in this setting. Methods and resultsA single-center observational study was conducted. Inclusion criteria were age≥75 and EF≤0.35. Six months after diagnosis, patients were divided into 3 groups depending on BB dose: no BB (NBB), low dose (<50% of the target dose) (LD), and high dose (≥50%) (HD). Two different analytical approaches were employed: multivariate Cox model and propensity-score (PS) matching. Outcomes were all-cause death and heart failure (HF) admission. We included 559 patients (134 NBB, 259 LD, and 166 HD) with median follow-up of 29.9months. There were 212 deaths (NBB: 70 (52.2%); LD: 94 (36.3%); and HD: 48 (28.9%)) and 171 HF admissions (NBB: 42 (31.3%); LD: 85 (32.8%); and HD: 44 (26.5%)). On multivariate analysis, both LD and HD were associated with improved survival, with no differences between them (HD vs. NBB=0.67, 95% CI=[0.46–0.98], p=0.037; HD vs. LD=1.03, 95% CI=[0.72–1.46], p=0.894; and LD vs. NBB=0.65, 95% CI=[0.48–0.90], p=0.009). However, BB therapy failed to show benefits in HF admissions (p=NS, for each comparison). PS-matched analysis included 198 patients, with similar results to those mentioned above. ConclusionsBB therapy was associated with a significant reduction in mortality among elderly patients with REF, regardless of dose. Nevertheless, it was not associated with a decrease in HF admissions. Further studies are needed to determine the optimal BB dose in these patients.

Initiation or maintenance of beta-blocker therapy in patients hospitalized for acute heart failure

Background Beta-blockers have been recommended for patients with heart failure and reduced ejection fraction for their long-term benefits. However, the tolerance to betablockers in patients hospitalized with acute heart failure should be evaluated. Objective To estimate the proportion of patients hospitalized with acute heart failure who can tolerate these agents in clinical practice and compare the clinical outcomes of patients who can and cannot tolerate treatment with beta-blockers. Setting Two reference hospitals in cardiology. Methods Retrospective cohort study of consecutive patients hospitalized for acute heart failure between September 2008 and May 2012. Population-based sample. During the study period, 325 patients were admitted consecutively, including 194 individuals with an acute heart failure diagnosis and systolic left ventricular dysfunction and ejection fraction ≤45%, who were candidates for the initiation or continuation of beta-blockers. Main outcome measure The percentage of patients intolerant to beta-blockers and the clinical characteristics of patients. Results On admission, 61.8% of patients were already using beta-blockers, and 73.2% were using beta-blockers on discharge. During hospitalization, 85% of patients used these agents for some period. The main reasons for not using betablockers were low cardiac output syndrome (24.4%), bradycardia (24.4%), severe hypotension or shock (17.8%), and chronic obstructive pulmonary disease (13.3%). Patients who were intolerant or did not use a beta-blocker had a longer hospital stay (18.3 vs. 11.0days; p<.001), greater use of vasoactive drugs (41.5 vs. 16.3%; p<.001, CI 1.80-7.35), sepsis and septic shock (RR=3.02; CI 95% 1.59-5.75), and higher mortality rate during hospitalization (22.6 vs. 2.9%; p<.001; CI 3.05-32.26). Conclusion Beta-blockers could be used in 73.2% of patients hospitalized for acute heart failure. Patients who can not tolerate BB presented a higher frequency of adverse clinical outcomes including frequency of sepsis, use of vasoactive drugs, average length of hospitalization, and death.

Trends for beta-blockers use in a large cohort of Polish hypertensive patients — Pol-Fokus Study

Background Beta-blockers remain one of the most frequently prescribed antihypertensive drug classes. The aim of the analysis was to evaluate characteristics of patients treated with beta-blockers and factors associated with the treatment of beta-blockers. Material and methods We analysed the data from the large cross-sectional study evaluating 12,375 patients treated for hypertension for at least one year. Results Overall, 7080 patients (57.2% of the whole group) were treated with beta-blockers. The rate of use of beta-blockers was higher in patients with diabetes (62.9 vs 55.6%), coronary artery disease (72.2 vs 46.4%), previous myocardial infarction (82.3 vs 54.1%), heart failure (73.1 vs 53.3%) and arrhythmias (73.1 vs 51.1%) than in patients without those conditions (all comparisons p < 0.001). Beta-blockers were used less frequently among patients with asthma/COPD than without asthma/COPD (54.0 vs 58.0%; p = 0.017). In patients aged 40 years and less, the compelling indications for these agents were found only in 21.7% of patients. In patients aged 40–65 years, none of compelling indications was found in 41.3% of patients. In patients 65 years or more, the most frequent compelling indications were coronary artery disease, previous myocardial infarction and heart failure, which were present in 70.1% of patients. Conclusions High utilization rate of beta-blockers in patients with hypertension, only second to renin-angiotensin blockers, has been shown. In middle age and, especially, in older patients it might reflect high cardiovascular burden of those patients, including coexistence of established cardiac disease. In younger patients beta-blockers are used more frequently with none of the compelling indications present.

Effect of different beta blockers on penile vascular velocities in hypertensive males

BackgroundBeta blockers are very commonly used as antihypertensive medications in young active individuals. This class has been accused of erectile dysfunction in patients taking them. Problems with erectile function can raise a concern in the treatment of hypertension and may influence the choice of treatment regimens and decisions to discontinue drugs. AimThe aim was to assess the effect of different beta blockers: nebivolol, atenolol, bisoprolol, and carvedilol on the penile arterial duplex velocities in hypertensive males. Methods and results108 non-smoking, non-diabetic, recently diagnosed hypertensive men, otherwise healthy, participated in the study. The patients were divided into four groups: Group 1 (24 patients) who were taking 5mg of nebivolol, Group 2 (28 patients) who took 100mg of atenolol, Group 3 (29 patients) who were taking 10mg of bisoprolol, and Group 4 (27 patients) who were on 25mg of carvedilol. The penile vascular velocities were measured before treatment and after a treatment phase of eight to twelve weeks of beta blocker antihypertensive treatment. We obtained a statistically significant diminish of the stimulated PSV with atenolol (P=0.03), bisoprolol (P=0.05), and carvedilol (P=0.02), while, with nebivolol the PSV did not show a significant change (P=0.7). There was also a significant decrease of the stimulated EDV with nebivolol (0.04) with no change with the other beta blockers. ConclusionNebivolol is a unique member of the beta blocker family showing neutral effects on the penile vascular velocities as compared to other beta blockers in hypertensive males.

Impact of beta-blocker therapy on thoracic aorta 3D wall shear stress in patients with bicuspid aortic valve

Background Beta-blockers are the recommended medical treatment for slowing ascending aorta (AAo) dilation in patients with bicuspid aortic valve (BAV). Wall shear stress (WSS) has been shown to promote endothelial cell dysfunction [1] and AAo WSS may play a role in aortic aneurysm growth. Time-resolved 3D phase contrast (4D flow) MRI allows for the quantification of 3D WSS regionally in the thoracic aorta. The aim of this study was to assess changes in thoracic aorta WSS associated with b-blocker therapy in BAV patients.