Long-term Β-blocker Therapy Research Articles

Randomized evaluation of routine beta-blocker therapy after myocardial infarction quality of life (RQoL): design and rationale of a multicentre, prospective, randomized, open, blinded endpoint study.

Most cases of acute myocardial infarction (MI) in Sweden are treated with long-term β-blocker therapy as secondary prevention. Case studies and patient reports have indicated negative effects of β-blockers including symptoms of depression, fatigue, sexual dysfunction, and general low mood, all related to reduced quality of life (QoL). To date, no recent large-scale, randomized trial has explored the effects of β-blockers on these factors. The ongoing Randomized Evaluation of Decreased Usage of beta-bloCkErs after myocardial infarction (REDUCE): quality of life (RQoL) study is a multicentre, prospective, randomized pre-specified substudy aiming to evaluate the effects of β-blockers on self-reported measures of QoL. Following randomized allocation to long-term β-blocker or no β-blocker treatment, patients complete a total of six baseline measures pertaining to QoL, sexual functioning, and perceived side effects. Data collection is optionally carried out online through a unique and secure portal and repeated again at two follow-up time points. Recruitment began in July 2018. Data from the first 100 patients showed that at the first follow-up, 93% had completed the questionnaires, which decreased to 81% at the second follow-up. The method of digital data collection was utilized by over half of the patients recruited so far. Data from the first 100 patients indicate success in terms of study design and recruitment. The RQoL substudy investigates the effects of β-blockers on self-reported measures of QoL in MI patients and will potentially contribute to the limited knowledge of QoL-related side effects reported in conjunction with β-blocker use. Eudra CT number, 2017-002336-17; Clinical trial.gov identifier, NCT03278509.

Association between Pre-Existing Long-Term β-Blocker Therapy and the Outcomes of Sepsis-Associated Coagulopathy: A Retrospective Study.

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.

Long-term β-blocker therapy and clinical outcomes after acute myocardial infarction in patients without heart failure: nationwide cohort study.

To investigate the association between long-term β-blocker therapy and clinical outcomes in patients without heart failure (HF) after acute myocardial infarction (AMI). Between 2010 and 2015, a total of 28970 patients who underwent coronary revascularization for AMI with β-blocker prescription at hospital discharge and were event-free from death, recurrent myocardial infarction (MI), or HF for 1 year were enrolled from Korean nationwide medical insurance data. The primary outcome was all-cause death. The secondary outcomes were recurrent MI, hospitalization for new HF, and a composite of all-cause death, recurrent MI, or hospitalization for new HF. Outcomes were compared between β-blocker therapy for ≥1 year (N = 22707) and β-blocker therapy for <1 year (N = 6263) using landmark analysis at 1 year after index MI. Compared with patients receiving β-blocker therapy for <1 year, those receiving β-blocker therapy for ≥1 year had significantly lower risks of all-cause death [adjusted hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.72-0.91] and composite of all-cause death, recurrent MI, or hospitalization for new HF (adjusted HR 0.82; 95% CI 0.75-0.89), but not the risks of recurrent MI or hospitalization for new HF. The lower risk of all-cause death associated with persistent β-blocker therapy was observed beyond 2 years (adjusted HR 0.86; 95% CI 0.75-0.99) but not beyond 3 years (adjusted HR 0.87; 95% CI 0.73-1.03) after MI. In this nationwide cohort, β-blocker therapy for ≥1 year after MI was associated with reduced all-cause death among patients with AMI without HF.

Do Patients need Lifelong β-Blockers after an Uncomplicated Myocardial Infarction?

The lifelong use of β-adrenoceptor antagonists (β-blockers) after a myocardial infarction (MI) has been the standard of care based on trials performed before the era of revascularization, when heart failure was common. Large randomized trials in the mid-1980s demonstrated that β-blockers played a major role in improving the in-hospital and long-term survival of patients admitted for MI. However, the implementation of rapid myocardial reperfusion led to a substantial survival benefit and a reduction of heart failure because of reduced infarct size. Modern large longitudinal registries did not provide sufficient evidence to support long-term β-blocker therapy in patients with uncomplicated acute MI. The long-term prescription of this therapy has become a matter of debate given the lack of contemporary evidence, frequent side effects, and treatment adherence issues. Furthermore, this shift into the reperfusion era led to a downgraded recommendation for the use of β-blockers in post-MI patients (class IIa B recommendation) in the 2017 European Society of Cardiology (ESC) recommendations for the treatment of ST-segment elevation MI (STEMI). Three large ongoing multicenter randomized trials (AβYSS, REDUCE-SWEDEHEART, and REBOOT-CNIC) are evaluating early discontinuation of β-blockers after an uncomplicated acute MI. The tested hypothesis is that β-blocker withdrawal is safe versus major adverse cardiovascular events and improves quality of life by reducing side effects. Thus, the present review summarizes the exhaustive evidence-based data for long-term β-blocker use after uncomplicated MI and the ongoing trials.

Predictors of β-blocker adherence in cardiac inherited disease

ObjectiveThe cardiac inherited disease (CID) population has suboptimal adherence to long-term β-blocker therapy, which is known to be a risk for sudden cardiac death. This study aimed to identify the...

Letter by Poullis Regarding Article, “Efficacy of Long-Term β-Blocker Therapy for Secondary Prevention of Long-Term Outcomes After Coronary Artery Bypass Grafting Surgery”

Zhang et al1 present important information with regard to β-blocker therapy and long-term outcomes in patients who have undergone coronary artery bypass graft surgery. Despite a meticulous analysis, a number of issues exist. Interestingly, in univariate analysis of patients with prior myocardial infarction, inconsistent use was significantly associated with a worse long-term survival compared with never and always users, implying that β-receptor upregulation, supersensitivity, and proarrhythmic potential are possible underlying mechanisms of their study findings rather than …

β-Blocker-Associated Risks in Patients With Uncomplicated Hypertension Undergoing Noncardiac Surgery.

Perioperative β-blocker strategies are important to reduce risks of adverse events. Effectiveness and safety may differ according to patients' baseline risk. To determine the risk of major adverse cardiovascular events (MACEs) associated with long-term β-blocker therapy in patients with uncomplicated hypertension undergoing noncardiac surgery. Association study based on in-hospital records and out-of-hospital pharmacotherapy use using a Danish nationwide cohort of patients with uncomplicated hypertension treated with at least 2 antihypertensive drugs (β-blockers, thiazides, calcium antagonists, or renin-angiotensin system [RAS] inhibitors) undergoing noncardiac surgery between 2005 and 2011. Various antihypertensive treatment regimens, chosen as part of usual care. Thirty-day risk of MACEs (cardiovascular death, nonfatal ischemic stroke, nonfatal myocardial infarction) and all-cause mortality, assessed using multivariable logistic regression models and adjusted numbers needed to harm (NNH). The baseline characteristics of the 14,644 patients who received β-blockers (65% female, mean [SD] age, 66.1 [12.0] years) were similar to those of the 40,676 patients who received other antihypertensive drugs (57% female, mean [SD] age, 65.9 [11.8] years). Thirty-day MACEs occurred in 1.3% of patients treated with β-blockers compared with 0.8% of patients not treated with β-blockers (P < .001). β-Blocker use was associated with increased risks of MACEs in 2-drug combinations with RAS inhibitors (odds ratio [OR], 2.16 [95% CI, 1.54-3.04]), calcium antagonists (OR, 2.17 [95% CI, 1.48-3.17]), and thiazides (OR, 1.56 [95% CI, 1.10-2.22]), compared with the reference combination of RAS inhibitors and thiazides. Results were similar for all-cause mortality. Risk of MACEs associated with β-blocker use seemed especially pronounced for patients at least 70 years old (number needed to harm [NNH], 140 [95% CI, 86-364]), for men (NNH, 142 [95% CI, 93-195]), and for patients undergoing acute surgery (NNH, 97 [95% CI, 57-331]), compared with patients younger than 70 years, women, and patients undergoing elective surgery, respectively. Antihypertensive treatment with a β-blocker may be associated with increased risks of perioperative MACEs and all-cause mortality in patients with uncomplicated hypertension.

Long-Term β-Blocker Therapy Decreases Blood Lactate Concentration in Severely Septic Patients*

Measurement of blood lactate concentration in the early management of sepsis is an important step in severity assessment. High blood lactate levels in the early phase of sepsis have classically been thought to be related to tissue hypoxia, but other factors could intervene. We hypothesized that the activation of glycolysis through β-adrenergic stimulation by endogenous catecholamines plays an important role in lactate production and that long-term β-blocker therapy could affect the lactate concentration in patients with severe sepsis and septic shock. Retrospective cohort study. Emergency department. Two hundred sixty patients with severe sepsis or septic shock were included. Twenty-five percent were previously treated with β-blockers. None. We recorded initial vital signs, the source of infection, mortality at 28 days, blood lactate concentration, and Predisposition Insult Response of Organ failure and Sequential Organ Failure Assessment scores using an electronic database. Blood lactate concentration was significantly lower in patients previously treated with β-blockers (3.9 ± 2.3 mmol/L vs 5.6 ± 3.6 mmol/L; p < 0.001). This difference was still significant after controlling for mortality (p < 0.005), for the level of the Predisposition Insult Response of Organ failure (p < 0.05) and Sequential Organ Failure Assessment (p < 0.05) scores, and for the source of infection (p < 0.05). Nearly four times more patients treated with β-blockers had normal blood lactate levels (p< 0.001). Only two factors were significantly and independently associated with normal blood lactate concentration during severe sepsis and septic shock: survival (p = 0.03) and β-blocker therapy (p = 0.01). Long-term β-blocker therapy decreases blood lactate concentration of severely ill septic patients at presentation. We conclude that the use of blood lactate measurement as a triage tool in the initial assessment of septic patients with β-blocker therapy may underestimate the severity of the sepsis.

Efficacy of Long-Term β-Blocker Therapy for Secondary Prevention of Long-Term Outcomes After Coronary Artery Bypass Grafting Surgery.

Conflicting results from recent observational studies have raised questions concerning the benefit of β-blockers for patients undergoing coronary artery bypass grafting (CABG). Furthermore, the efficacy of long-term β-blocker therapy in CABG patients after hospital discharge is uncertain. The study included 5926 consecutive patients who underwent CABG and were discharged alive. The prevalence and consistency of β-blocker use were determined in patients with and without a history of myocardial infarction (MI). β-Blockers were always used in 1280 patients (50.9%) with and 1642 patients (48.1%) without previous MI after CABG. Compared with always users (n=2922, 49.3%), the risk of all-cause death was significantly higher among inconsistent β-blocker users (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.50-2.57), and never using β-blockers was associated with increased risk of both all-cause death (HR, 1.42; 95% CI, 1.01-2.00) and the composite of adverse cardiovascular events (HR, 1.29; 95% CI, 1.10-1.50). In the cohort without MI, the HR for all-cause death was 1.70 (95% CI, 1.17-2.48) in inconsistent users and 1.23 (95% CI, 0.76-1.99) in never users. In the MI cohort, mortality was higher for inconsistent users (HR, 2.14; 95% CI, 1.43-3.20) and for never users (HR, 1.59; 95% CI, 1.07-2.63). Consistent results were obtained in equivalent sensitivity analyses. In patients with or without previous MI undergoing CABG, the consistent use of β-blockers was associated with a lower risk of long-term mortality and adverse cardiovascular events. Strategies should be developed to understand and improve discharge prescription of β-blockers and long-term patient adherence.

Cardiopulmonary reserve as determined by cardiopulmonary exercise testing correlates with length of stay and predicts complications after radical cystectomy.

To investigate whether poor preoperative cardiopulmonary reserve and comorbid state dictate high-risk status and can predict complications in patients undergoing radical cystectomy (RC). In all, 105 consecutive patients with transitional cell carcinoma (TCC; stage T1-T3) undergoing robot-assisted (38 patients) or open (67) RC in a single UK centre underwent preoperative cardiopulmonary exercise testing (CPET). Prospective primary outcome variables were all-cause complications and postoperative length of stay (LOS). Binary logistic regression analysis identified potential predictive factor(s) and the predictive accuracy of CPET for all-cause complications was examined using receiver operator characteristic (ROC) curve analysis. Correlations analysis employed Spearman's rank correlation and group comparison, the Mann-Whitney U-test and Fisher's exact test. Any relationships were confirmed using the Mantel-Haenszel common odds ratio estimate, Kaplan-Meier analysis and the chi-squared test. The anaerobic threshold (AT) was negatively (r = -206, P = 0.035), and the ventilatory equivalent for carbon dioxide (VE/VCO₂) positively (r = 0.324, P = 0.001) correlated with complications and LOS. Logistic regression analysis identified low AT (<11 mL/kg/min), high VE/VC0₂ (≥33) and hypertension as significant factors, such that, in their presence patients were 5.55-times more likely to have complications at 90 days postoperatively [P = 0.001, 95% confidence interval (CI) 2.2-13.9]. ROC analysis showed a high significance (area under the curve 0.78, 95% CI 0.69-0.87; P < 0.001). In addition, based on CPET criteria >50% of patients presenting for RC had significant heart failure, whereas preoperatively only very few (2%) had this diagnosis. Analysis using the Mann-Whitney test showed that a VE/VCO₂ ≥33 was the most significant determinant of LOS (P = 0.004). Kaplan-Meier analysis showed that patients in this group had an additional median LOS of 4 days (P = 0.008). Finally, patients with an American Society of Anesthesiologists grade of 3 (ASA 3) and those on long-term β-blocker therapy were found to be at particular risk of myocardial infarction (MI) and death after RC with odds ratios of 4.0 (95% CI 1.05-15.2; P = 0.042) and 6.3 (95% CI 1.60-24.8; P = 0.008). Patients with poor cardiopulmonary reserve and hypertension are at higher risk of postoperative complications and have increased LOS after RC. Heart failure is known to be a significant determinant of perioperative death and is significantly under diagnosed in this patient group.

Beta-Blocking Agents for Surgery: Influence on Mortality and Major Outcomes. A Meta-Analysis

To re-evaluate the effects of perioperative beta-blockade on mortality and major outcomes after surgery. A meta-analysis of parallel randomized, controlled trials published in English. A university-based electronic search. Patients undergoing surgery. Two interventions were evaluated: (1) Stopping or continuing a β-blocker in patients on long-term β-blocker therapy; and (2) Adding a β-blocker for the perioperative period. Stopping a β-blocker before the surgery did not change the risk of myocardial infarction (3 studies including 97 patients): risk ratio (RR), 1.08 (95% confidence interval 0.30, 3.95); I(2), 0%. Adding a β-blocker reduced the risk of death at 1 year: RR, 0.56 (0.31, 0.99); I(2), 0%; p = 0.046; number needed to treat 28 (19, 369) (4 studies with 781 patients). Adding a β-blocker reduced the 0-to-30 day risk of myocardial infarction: RR, 0.65 (0.47, 0.88); I(2), 12.9%; p = 0.006 (15 studies with 12,224 patients), but increased the risk of a stroke: RR, 2.18 (1.40, 3.38); I(2), 0%; p = 0.001 (8 studies with 11,737 patients); number needed to harm 177 (512, 88). β-blockers reduced the 1-year risk of death, and this effect seemed greater than the risk of inducing a stroke.

Impact of Beta Blockade Therapy on Long-Term Mortality After ST-Segment Elevation Acute Myocardial Infarction in the Percutaneous Coronary Intervention Era

Although clinical guidelines recommend long-term β-blocker (BB) therapy to decrease mortality after acute myocardial infarction, these recommendations are based predominantly on evidence from before the reperfusion and thrombolytic eras. To investigate the effects of BB therapy for patients with acute myocardial infarctions on mortality in the percutaneous coronary intervention era, a total of 5,628 consecutive patients who were admitted <24 hours after the onset of ST-segment elevation myocardial infarction, treated with emergent percutaneous coronary intervention, and discharged alive were studied. During a median follow-up period of 1,430 days, mortality rates did not differ between patients with and without BB therapy (5.2% vs 6.2%, p= 0.786). Multivariate analysis revealed that BB treatment was not associated with a reduced risk for mortality (hazard ratio 0.935, 95% confidence interval 0.711 to 1.230, p= 0.534). The results of propensity score matching also indicated that the mortality rates did not differ between the 2 groups. However, subgroup analyses among matched populations revealed that BB treatment was associated with a significantly lower mortality risk for high-risk patients, who were defined as those with Global Registry of Acute Coronary Events (GRACE) risk scores ≥121 (hazard ratio 0.596, 95% confidence interval 0.416 to 0.854, p= 0.005) or those administered diuretics (hazard ratio 0.602, 95% confidence interval 0.398 to 0.910, p= 0.016), but not for lower risk patients. In conclusion, BB treatment was associated with reduced long-term mortality in patients after ST-segment elevation myocardial infarction at higher risk, but not in those at lower risk. Although randomized controlled studies are warranted to confirm these results, the implementation of BB therapy for discharged patients with ST-segment elevation myocardial infarction may need to be assessed on the basis of individual mortality risk in the percutaneous coronary intervention era.

Effect of β-Blocker Cessation on Chronotropic Incompetence and Exercise Tolerance in Patients With Advanced Heart Failure

Chronotropic incompetence is defined as the inability to reach 80% of heart rate (HR) reserve or 80% of the maximally predicted HR during exercise. The presence of chronotropic incompetence is associated with reduced peak oxygen consumption, and rate-responsive pacing therapy is under investigation to improve exercise capacity in heart failure (HF). However, uncertainty exists about whether chronotropic incompetence and reduced exercise tolerance in HF are attributable to β-blockade. Subjects with HF and receiving long-term β-blocker therapy underwent cardiopulmonary exercise tolerance testing under 2 conditions in random sequence: (1) after a 27-hour washout period (Off-BB) and (2) 3 hours after β-blocker ingestion (On-BB). Norepinephrine levels were drawn at rest and at peak exercise. β1-response to norepinephrine was assessed using the chronotropic responsiveness index: ΔHR/Δlog norepinephrine. Nineteen patients with systolic HF (left ventricular ejection fraction, 22.8±7.7%) were enrolled. Mean age was 49.4±12.3 years. Average carvedilol equivalent dose was 29.1±17.0 mg daily. Peak HR off/on β-blockers was 62.7±18.7% and 51.4±18.2% HR reserve (P<0.01) and 79.1±11.0% and 70.3±12.3% maximally predicted HR (P<0.01). For the Off-BB and On-BB conditions, the respiratory exchange ratios were 1.05±0.06 and 1.05±0.10 (P=0.77), respectively, confirming maximal and near identical effort in both conditions. The peak oxygen consumption was 16.6±3.34 and 15.9±3.31 mL/kg/min (P=0.03), and the chronotropic responsiveness index was 19.3±7.2 and 16.2±7.1 (P=0.18). Acute β-blocker cessation does not normalize the chronotropic response to exercise in patients with advanced HF and chronotropic incompetence.

Response to Catecholamine Stimulation of Polymorphisms of the Beta-1 and Beta-2 Adrenergic Receptors

Previous studies have demonstrated that β-adrenergic receptor polymorphisms affect outcomes in patients with heart failure or after an acute coronary syndrome. Whether β-adrenergic polymorphisms influence catecholamine responses in patients with cardiovascular disease is not known. Cardiovascular responses to the β1-receptor agonist dobutamine and the β2-receptor agonist terbutaline were studied using gated blood pool scintigraphy in 21 patients on long-term β-blocker therapy. Heart rate (HR), stroke volume (SV), and cardiac output (CO) increased, and end-systolic volume decreased with dobutamine and terbutaline. Changes in HR and CO with dobutamine were higher for those with ≥1 β1 Arg389 allele than those homozygous for the Gly389 allele (change in HR 15 vs 1 beat/min, p = 0.02; change in CO 2.4 vs 1.0 L/min, p = 0.02). Increases in HR, CO, and SV with terbutaline were greater for those homozygous for the β2 Glu27 allele than those with ≥1 Gln27 allele (change in HR 13.7 vs 4.8 beats/min, p = 0.048; change in CO 3.1 vs 1.6 L/min, p = 0.034; change in SV 28.3 vs 14.8 ml, p = 0.045). Changes in CO and volume with terbutaline were greater in those with an ejection fraction <40% than in those with an ejection fraction ≥40%. In conclusion, β-receptor gene variants significantly influence inotropic and chronotropic responses to β-agonist exposure in patients on β-blocker therapy.

Beta-Blocker Withdrawal Among Patients Presenting for Surgery from Home

This study sought to measure the prevalence of perioperative β-blocker noncompliance by patients who were prescribed long-term β-blocker therapy and presented for surgery from home. The effect of patient noncompliance on the presenting heart rate on the day of surgery also was examined. Prospective observational study with outcome data obtained from reviews of medical records. The preoperative clinic and operating rooms of a Veterans Administration hospital. Patients on long-term β-blocker therapy who presented from home for surgery. None. Demographic and comorbidity data and data on self-reported compliance to β-blocker therapy, vital signs on the initial day of surgery, and recent ambulatory vital signs were collected. Ten of 50 subjects (20%; 95% confidence interval, 9-31) reported not taking their β-blocker on the day of surgery. These self-reported nonadherers exhibited a higher presenting heart rate on the day of surgery than adherent subjects (median, 78 v 65 beats/min; p = 0.02 by Wilcoxon rank-sum test). The difference-in-difference analysis in heart rate between baseline primary care and the day of surgery also was statistically significant between compliant and noncompliant subjects (-7 v + 12.5 beats/min; p < 0.00001). Patient self-report and physiologic data documented a failure to take β-blockers and possible β-blocker withdrawal in 20% of patients who presented for surgery from home. If these findings are confirmed in larger studies, improved patient understanding of and compliance with medication instructions during preoperative visits should be a focus of future quality improvement initiatives.

Ivabradine Versus Metoprolol for Heart Rate Reduction Before Coronary Computed Tomography Angiography

Several studies have demonstrated the correlation of heart rate (HR) and image quality in coronary computed tomography angiography. Beta-blocker administration is critical because of its negative inotropic effect. Ivabradine is a selective HR-lowering agent that exclusively inhibits the I(f) current in sinoatrial node cells without having any effect on cardiac contractility or atrioventricular conduction. A total of 120 patients were randomized to oral premedication with ivabradine 15 mg or metoprolol 50 mg. HR and blood pressure (BP) were measured before the administration of premedication and immediately before coronary computed tomographic angiography. The mean time between premedication administration and follow-up was 108 ± 21.5 minutes for ivabradine and 110 ± 22.2 minutes for metoprolol (p = NS). When comparing groups, there were no significant differences in reduction of HR (-11.83 ± 8.6 vs -13.20 ± 7.8 beats/min, p = NS) and diastolic BP (-5.05 ± 14.2 mm Hg vs -4.08 ± 10.8 mm Hg, p = NS), whereas the decrease of systolic BP was significantly lower in patients who received ivabradine compared to those in the metoprolol group (-3.95 ± 13.6 vs -13.65 ± 17.3 mm Hg, p <0.001). In the subgroup of patients who were receiving long-term β-blocker therapy, significantly stronger HR reduction was achieved with ivabradine (-13.19 ± 5.4 vs -10.04 ± 6.0 beats/min, p <0.05), while the decrease in systolic BP was less (-2.00 ± 13.6 vs -15.04 ± 20.8 mm Hg, p <0.05) compared to metoprolol. In conclusion, ivabradine decreases HR before coronary computed tomographic angiography sufficiently, with significantly less depression of systolic BP compared to metoprolol.

Long-term β-blocker therapy improves diastolic function even without the therapeutic effect on systolic function in patients with reduced ejection fraction

The beneficial effects of beta-blocker therapy on the clinical outcomes of heart failure with reduced ejection fraction (HFREF) are attributed to the improvement in ejection fraction (EF) and left ventricular (LV) reverse remodeling. Previous studies only reported the beta-blocker therapy-induced improvement of diastolic function accompanied by the increase in EF in HFREF patients. This retrospective study aimed to elucidate whether beta-blocker therapy improves diastolic function even without an increase in EF. Out of the consecutive 11,830 echocardiographic reports, HFREF patients without an increase in EF following long-term beta-blocker therapy comprised the study subjects (n=19). During the mean follow-up of 17 months, beta-blocker therapy significantly decreased peak mitral E-wave velocity (70±25-50±18 cm/s, p<0.01) and ratio of peak mitral E- to A-wave velocities (E/A ratio) (1.4±0.8-0.9±0.4, p<0.05), prolonged deceleration time of the mitral E-wave velocity (DcT) (167±54-206±61 ms, p<0.05), and improved New York Heart Association functional class (2.3±0.7-1.8±0.4, p<0.01) without changes in LV volume. Because DcT and E/A ratio are well known to correlate with LV filling pressures in patients with reduced EF, our results indicate a reduction in LV filling pressures without changes in LV volume, suggesting a reduction in LV stiffness. Thus, long-term beta-blocker therapy is likely to improve diastolic function even without a concomitant increase in EF in HFREF patients, which may be also responsible for the beta-blocker-induced improvement of their symptoms of heart failure.

Acute pulmonary edema due to phenylephrine injection in patient receiving long-term beta-blocker therapy: A case report.

During administration of anesthesia, intraoperative blood pressure control is very important. Sometimes a hypertensive or anti-hypertensive agent is used in order to maintain blood pressure at an adequate level; alpha-agonist and beta-blocker are drugs frequently used. Alpha-agonists are used in various ways including their application together with local anesthetics during an operation for the purpose of vasoconstriction, to control systemic absorption of local anesthetics, to extend the duration of action, or to reduce bleeding from the surgical site. In addition, alpha-agonists are used in cardiopulmonary resuscitation. Beta-blockers are used widely as a therapeutic agent for hypertension, angina, and arrhythmia, and to lower portal pressure in liver cirrhosis. Here, we are reporting the case of acute pulmonary edema that occurred after the administration of phenylephrine, in order to maintain blood pressure in a 52-year-old female patient with liver cirrhosis. The patient was underwent emergent decompressive craniectomy for intracranial hemorrhage without acknowledging her long-term use of a beta-blocker medication.

Decreased heart rate recovery after exercise in patients with congestive heart failure: Effect of β-blocker therapy

Background: Decreased heart rate recovery (HRR) is a predictor of mortality in patients with coronary artery disease and preserved left ventricular function. We investigated the changes in HRR and assessed the impact of β-blockade therapy on these parameters in patients with symptomatic congestive heart failure (CHF). Methods and Results: HRR, defined as the difference from peak exercise heart rate (HR) to HR measured at 1, 2, and 3 minutes after maximal exercise test, was studied in 23 stable CHF patients and 12 healthy subjects. Patients with CHF performed a maximal exercise test using a Ramp protocol before and after 6 months of therapy with either metoprolol or carvedilol. Patients with CHF exhibited a significantly attenuated HRR compared with healthy subjects at 1 minute (17.8 ± 5.8 versus 26.8 ± 16.2 beats), 2 minutes (34.0 ± 10.6 versus 48.0 ± 11.2 bpm) and 3 minutes (41.0 ± 12.4 versus 60.0 ±12.4 bpm) after exercise (P <.05 for all parameters). β-blocker therapy for 6 months did not significantly improve HRR. Conclusion: HRR is markedly attenuated in stable CHF patients compared with healthy subjects. Long-term β-blocker therapy appears to cause no significant improvement in HRR up to 3 minutes after maximal exercise.

Changes in the occurrence of mechanical alternans after long-term beta-blocker therapy in patients with chronic heart failure.

Mechanical alternans has been observed in patients with severe congestive heart failure, and the phenomenon is considered to be a terminal sign. Therapeutic strategies for chronic heart failure have significantly developed, but it is uncertain whether patients with mechanical alternans can be effectively treated or not. Seventeen consecutive patients with dilated cardiomyopathy were enrolled: 11 were treated with beta-blockers on conventional therapeutic regimens and 6 patients were not indicated for or were unable to continue beta-blockade. Mechanical alternans was detected during cardiac catheterization in the patients under physiologic tachycardia (110 beats/min) and stepwise dobutamine loading. In the initial study, mechanical alternans occurred in 70.6% of the patients: 8 of the 11 being treated with beta-blockers and 4 of the 6 without beta-blockade therapy. In the second study, none of the patients taking beta-blockers showed mechanical alternans under the same protocol; the occurrence of mechanical alternans did not change in the patients who were not being treated with beta-blockers. The left ventricular ejection fraction increased in patients whose mechanical alternans could not be induced during the follow up, but decreased in the patients in whom mechanical alternans was repeatedly inducible. It is concluded that mechanical alternans is associated with the failing myocardium and may be potentially correctable.