Beta-adrenergic Blocker Therapy Research Articles

β-blockers in advanced cirrhosis: More friend than enemy

Nonselective beta-adrenergic blocker (NSBB) therapy for the prevention of initial and recurrent gastrointestinal bleeding in cirrhotic patients with gastroesophageal varices has been used for the past four decades. NSBB therapy is considered the cornerstone of treatment for varices, and has become the standard of care. However, a 2010 study from the group that pioneered β-blocker therapy suggested a detrimental effect of NSBBs in decompensated cirrhosis, especially in patients with refractory ascites. Since then, numerous additional studies have incompletely resolved whether NSBBs are deleterious, although more recent evidence weighs against a harmful effect. The possibility of a “therapeutic window” has also been raised. We aimed to review the literature to analyze the pros and cons of using NSBBs in patients with cirrhosis, not only with respect to bleeding or mortality but also to other potential benefits and risks. β-blockers are highly effective in preventing first bleeding and recurrent bleeding. Furthermore, NSBBs improve congestion/ischemia of the gut mucosa, decrease intestinal permeability, and therefore indirectly alleviate systemic inflammation. β-blockers shorten the electrocardiographic prolonged QTc interval and may also decrease the incidence of hepatocellular carcinoma. On the other hand, the possibility of deleterious effects in cirrhosis has not been completely eliminated. NSBBs may be associated with an increased risk of portal vein thrombosis, although this could be correlational artifact. Overall, we conclude that β-blockers in cirrhosis are much more of a friend than enemy.

Risk of cardiac events in Long QT syndrome patients when taking antiseizure medications

Many antiseizure medications (ASMs) affect ion channel function. We investigated whether ASMs alter the risk of cardiac events in patients with corrected QT (QTc) prolongation. The study included people from the Rochester-based Long QT syndrome (LQTS) Registry with baseline QTc prolongation and history of ASM therapy (n=296). Using multivariate Anderson-Gill models, we assessed the risk of recurrent cardiac events associated with ASM therapy. We stratified by LQTS genotype and predominant mechanism of ASM action (Na+ channel blocker and gamma-aminobutyric acid modifier.) There was an increased risk of cardiac events when participants with QTc prolongation were taking vs off ASMs (HR 1.65, 95% confidence interval [CI] 1.36-2.00, P<0.001). There was an increased risk of cardiac events when LQTS2 (HR 1.49, 95% CI 1.03-2.15, P=0.036) but not LQTS1 participants were taking ASMs (interaction, P=0.016). Na+ channel blocker ASMs were associated with an increased risk of cardiac events in participants with QTc prolongation, specifically LQTS2, but decreased risk in LQTS1. The increased risk when taking all ASMs and Na+ channel blocker ASMs was attenuated by concurrent beta-adrenergic blocker therapy (interaction, P<0.001). Gamma-aminobutyric acid modifier ASMs were associated with an increased risk of events in patients not concurrently treated with beta-adrenergic blockers. Female participants were at an increased risk of cardiac events while taking all ASMs and each class of ASMs. Despite no change in overall QTc duration, pharmacogenomic analyses set the stage for future prospective clinical and mechanistic studies to validate that ASMs with predominantly Na+ channel blocking actions are deleterious in LQTS2, but protective in LQTS1.

A nurse-led up-titration clinic improves chronic heart failure optimization of beta-adrenergic receptor blocking therapy--a randomized controlled trial.

BackgroundBeta-adrenergic blockade has been shown to improve left ventricular function, reduce hospital admissions and improve survival in chronic heart failure with reduced ejection fraction (HFrEF), with mortality reduction starting early after beta-adrenergic receptor blocker initiation and being dose-related. The aim of this pilot study was to determine the effectiveness of a nurse-led titration clinic in improving the time required for patients to reach optimal doses of the beta-adrenergic receptor blocking agents.MethodWe conducted a prospective pilot randomized controlled trial. Twenty eight patients with CHF were randomized to optimisation of beta-adrenergic receptor blocker therapy over six months by either a nurse-led titration (NLT) clinic, led by a nurse specialist with the support of a cardiologist in a CHF clinic, or by their primary care physician (usual care (UC)). The primary endpoint was time to maximal beta-adrenergic receptor blocker dose. The secondary end-point was the proportion of patients reaching the target dose of beta-adrenergic receptor blocker by six months.ResultsThe patients were predominantly men (72%), age 67 ± 16 years; New York Heart Association (NYHA) functional class I (32%), II (44%) and III (20%); baseline left ventricular ejection fraction 33 ± 10%, and a low mean Charlson co-morbidity score of 2.5 ± 1.4. The time to maximum dose was shorter in the NLT group compared to the UC group (90 ± 14 vs 166 ± 8 days, p < 0.0005). At six months, in the NLT group there were nine patients (82%) on high dose and one patient (9%) on low dose beta-adrenergic receptor blocker compared to the UC group with five (42%) patients reaching maximum dose and five (42%) patients on low dose (p = 0.04). The patients allocated to the NLT group also had significantly less worsening of depression between baseline and six months (p = 0.006).ConclusionA NLT clinic improves optimisation of beta-adrenergic receptor blocker therapy through increasing the proportion of patients reaching maximal dose and facilitating rapid up-titration of beta-adrenergic receptor blocker agents in patients with chronic HFrEF.Trial registrationAustralian Clinical Trials Registry (ACTRN012606000383561).

Effects of Obesity and Subsequent Weight Reduction on Left Ventricular Function

Obesity is reaching epidemic proportions in the United States. Obesity adversely affects the circulatory system with resultant endothelial dysfunction, which promotes systemic hypertension, coronary artery disease, and vascular calcification. It is believed that the release of adipokines is responsible for this effect. In addition, obesity causes intrinsic changes in the heart including an increase in left ventricular (LV) mass, LV hypertrophy, LV dilatation, left atrial dilatation, and diastolic, as well as systolic dysfunction in some cases. The combination of increased adipose cells and an increase lean muscle mass in obese patients results in high cardiac output and an accompanying increased circulating volume leading to these adaptive changes. Weight loss by means of caloric restriction or surgery results in favorable hemodynamic changes referred to as "reverse remodeling." Regression of LV mass and chamber size has been shown universally. However, some studies have failed to reveal improvement in diastolic function possibly because of confounders such as nutritional deficiency that may occur after weight loss surgery. Some evidence seems to suggest that the greatest regression of LV mass and LV hypertrophy may occur when weight loss is combined with beta-adrenergic blocker therapy (in those who have an indication for the drug) when compared with other antihypertensive drugs versus weight loss alone.

Mechanisms of Pharmacogenomic Effects of Genetic Variation within the Cardiac Adrenergic Network in Heart Failure

One of the goals of pharmacogenomics is the use of genetic variants to predict an individual's response to treatment. Although numerous candidate and genome-wide associations have been made for cardiovascular response-outcomes, little is known about how a given polymorphism imposes the phenotype. Such mechanisms are important, because they tie the observed human response to specific signaling alterations and thus provide cause-and-effect relationships, aid in the design of hypothesis-based clinical studies, can help to devise workaround drugs, and can reveal new aspects of the pathophysiology of the disease. Here we discuss polymorphisms within the adrenergic receptor network in the context of heart failure and beta-adrenergic receptor blocker therapy, where multiple approaches to understand the mechanism have been undertaken. We propose a comprehensive series of studies, ranging from transfected cells, transgenic mice, and ex vivo and in vitro human studies as a model approach to explore mechanisms of action of pharmacogenomic effects and extend the field beyond observational associations.

Management of Acute Decompensated Heart Failure

Acute decompensated heart failure is the most common cause for hospitalization among patients over 65 years of age. It may result from new onset of ventricular dysfunction or, more typically, exacerbation of chronic heart failure symptoms. In-hospital mortality remains high for both systolic and diastolic forms of the disease. Therapy is largely empirical as few randomized, controlled trials have focused on this population and consensus practice guidelines are just beginning to be formulated. Treatment should be focused upon correction of volume overload, identifying potential precipitating causes, and optimizing vasodilator and beta-adrenergic blocker therapy. The majority of patients (>90%) will improve without the use of positive inotropic agents, which should be reserved for patients with refractory hypotension, cardiogenic shock, end-organ dysfunction, or failure to respond to conventional oral and/or intravenous diuretics and vasodilators. The role of aldosterone antagonists, biventricular pacing, and novel pharmacological agents including vasopressin antagonists, endothelin blockers, and calcium-sensitizing agents is also reviewed.

β&lt;SUB&gt;2&lt;/SUB&gt;-Adrenergic Receptor Genotype and Survival Among Patients Receiving β-Blocker Therapy After an Acute Coronary Syndrome

Previous data support an association between polymorphisms of the beta1- and beta2-adrenergic receptors (ADRB1 and ADRB2) and surrogate end points of response to beta-adrenergic blocker therapy. However, no associations between these polymorphisms and mortality have been demonstrated. To evaluate the effect of ADRB1 Arg389Gly (1165 CG), Ser49Gly (145 AG), and ADRB2 Gly16Arg (46 GA), Gln27Glu (79 CG) genotypes on survival among patients discharged with prescribed beta-blockers after an acute coronary syndrome (ACS). Prospective cohort study of 735 ACS patients admitted to 2 Kansas City, Mo, medical centers between March 2001 and October 2002; 597 patients were discharged with beta-blocker therapy. Multivariable-adjusted time to all-cause 3-year mortality. There were 84 deaths during follow-up. There was a significant association between ADRB2 genotype and 3-year mortality among patients prescribed beta-blocker therapy. For the 79 CG polymorphism, Kaplan-Meier 3-year mortality rates were 16% (35 deaths), 11% (27 deaths), and 6% (4 deaths) for the CC, CG, and GG genotypes, respectively (P = .03; adjusted hazard ratios [AHRs], 0.51 [95% confidence interval {CI}, 0.30-0.87] for CG vs CC and 0.24 (95% CI, 0.09-0.68) for GG vs CC, P = .004). For the ADRB2 46 GA polymorphism, 3-year Kaplan-Meier mortality estimates were 10% (17 deaths), 10% (28 deaths), and 20% (20 deaths) for the GG, GA, and AA genotypes, respectively (P = .005; AHRs, 0.48 [95% CI, 0.27-0.86] for GA vs AA and 0.44 [95% CI, 0.22-0.85] for GG vs AA, P = .02). No mortality difference between genotypes was found among patients not discharged with beta-blocker therapy for either the 79 CG or 46 GA polymorphisms (P = .98 and P = .49, respectively). The ADRB2 diplotype and compound genotypes were predictive of survival in patients treated with beta-blockers (P = .04 and P = .002; AHRs, 5.36 [95% CI, 1.83-15.69] and 2.41 [95% CI, 0.86-6.74] for 46 A homozygous and composite heterozygous vs 79 G homozygous, respectively). No association of the ADRB1 variants with mortality was observed in either the beta-blocker or no beta-blocker groups. Patients prescribed beta-blocker therapy after an ACS have differential survival associated with their ADRB2 genotypes. Further assessment of the benefits of beta-blocker therapy in high-risk genotype groups may be warranted.

Sympathetic neuronal regulation of the heart in aging and heart failure

The documentation of preferential activation of the cardiac sympathetic outflow in patients with heart failure swept aside an entrenched notion that there was a functional sympathetic denervation of the failing heart and provided a theoretical basis for the clinical evaluation of beta-adrenergic blocker therapy in this condition. The demonstration that heightened sympathetic nervous system activity is central to the pathogenesis and progression of congestive heart failure (CHF) has now led to the rational use of beta-adrenoceptor blockade in CHF. More recently, it has also emerged that the aging heart exhibits some of the characteristic changes in autonomic control which are seen in CHF. Accordingly, alterations in cardiac sympathetic nerve function are now thought to contribute also to the pathophysiology of the aging heart. Furthermore, there is evidence that in humans, sympathoexcitatory rostral projections of brainstem noradrenergic neurons to the forebrain are important in the sympathetic nervous activation of both heart failure and aging. Given these similarities, in this review we compare and contrast the neurobiology of the sympathetic nervous system in the failing heart and the healthy, aging heart, and consider whether the sympathetic activation accompanying aging may, perhaps, underlie and contribute to the neural pathophysiology of heart failure. Our conclusion is, on balance, that this proposition is not supported by the available evidence.

Calcium Channel Antagonism Reduces Exercise‐Induced Ventricular Arrhythmias in Catecholaminergic Polymorphic Ventricular Tachycardia Patients with RyR2 Mutations

Calcium channel antagonism in RyR2 defects. Recently, gain-of-function mutations of cardiac ryanodine receptor RyR2 gene have been identified as a cause of familial or catecholaminergic polymorphic ventricular tachycardia. We examined the influence of the calcium channel blockers, verapamil and magnesium, on exercise-induced ventricular arrhythmias in patients with RyR2 mutations. Six molecularly defined catecholaminergic polymorphic ventricular tachycardia patients, all carrying a RyR2 mutation and on beta-adrenergic blocker therapy, underwent exercise stress test four times: at baseline, after verapamil and magnesium sulphate infusions, and finally, without interventions. The number of isolated and successive premature ventricular complexes during exercise ranged from 40 to 374 beats (mean 165 beats) at baseline, and was reduced during verapamil by 76+/-17% (P<0.05). Premature ventricular complexes appeared later and at higher heart rate during verapamil than at baseline (119+/-21 vs. 127+/-27 min-1, P<0.05). Magnesium did not inhibit the arrhythmias. Results in the fourth exercise stress test without interventions were similar to those in the first baseline study. This study provides the first in vivo demonstration that a calcium channel antagonist, verapamil, can suppress premature ventricular complexes and nonsustained ventricular salvoes in catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations. Modifying the abnormal calcium handling by calcium antagonists might have therapeutic value.

A new oral therapy for long QT syndrome: Long-term oral potassium improves repolarization in patients with HERGmutations

ObjectivesWe sought to determine whether oral potassium supplementation safely increases serum K+and results in sustained improvement of repolarization parameters in long QT syndrome type 2 (LQT2) subjects. BackgroundMutations in HERG(LQT2), the gene encoding the rapid delayed rectifier K+current IKr, account for a significant proportion of congenital long QT syndrome (LQTS). The magnitude of IKris paradoxically increased by an increase in extracellular K+. We tested the hypothesis that long-term oral potassium supplementation results in a mild, sustainable increase in serum K+that improves repolarization abnormalities in subjects with LQT2. MethodsAfter an initial evaluation consisting of electrocardiography, electrolytes, blood urea nitrogen, and creatinine, escalating doses of potassium chloride (KCl) and spironolactone were administered to eight subjects with six distinct HERGmutations. Medications were continued for four weeks, at which time, the final evaluation was undertaken. Beta-adrenergic blocking therapy was maintained. ResultsThe subjects ranged in age from 11 to 52 years. The average daily KCl and spironolactone dose was 3.3 ± 1.5 mEq/kg and 3.5 ± 1.2 mg/kg, respectively, and this regimen resulted in an increase in serum K+from 4.0 ± 0.3 to 5.2 ± 0.3 mEq/l. There were no serious complications associated with therapy. The increase in serum K+resulted in a decrease in the corrected QT interval from 526 ± 94 to 423 ± 36 ms (mean ± SD; lead V2). Both QT dispersion and T-wave morphology improved in most subjects. ConclusionsLong-term oral potassium administration increases serum K+in patients with LQT2. This can be achieved safely and results in improvement in repolarization. Further studies are warranted to determine whether this will reduce the incidence of life-threatening events in LQTS patients.

Postprandial lipemia and beta-adrenergic blocker therapy after a first acute coronary event

Postprandial lipemia and beta-adrenergic blocker therapy after a first acute coronary event

Diastolic dysfunction in the presence of left ventricular systolic dysfunction: implications of beta-adrenergic blocking therapy.

The contribution of left ventricular diastolic dysfunction to the impairment in overall left ventricular performance in patients with systolic dysfunction is underappreciated. This article summarizes the available data on diastolic dysfunction in patients with congestive heart failure in which the predominant abnormality was thought to be left ventricular systolic dysfunction. The prevalence and identification of diastolic abnormalities and their clinical relevance are addressed, particularly the role of beta-adrenergic blocking therapy. The potential benefits of beta-adrenergic blocking therapy to diastolic performance are discussed from both a hemodynamic and clinical standpoint, with the implication that diastolic performance and its modulation should be considered in future investigations. (c)2001 by CHF, Inc.

Beta-adrenergic receptor blocking therapy for congestive heart failure: an overview

It is uncommon for clinical trials to be prematurely terminated because of formidable evidence in favour ofa particular agent or strategy and rare for such trials to be reported in lay press. This is what has precisely happened with regard to beta-adrenoceptor blocking therapy in patients with congestive heart failure twice once in 1996 and again in March, 2000. The drug in question has been carvedilol (a beta-adrenergic receptor blocking agent) and the trials were Carvedilol US Heart Failure Study and GOPERNICUS (Carvedilol Prospective Randomised Cumulative Outcome Study). The therapy in patients of congestive heart failure has shown a remarkable change over a period of last three decades ever since it was shown by a Swedish team that in some patients with heart failure, beta-blocking agents can cause symptomatic improvement in refractory heart failure. The current theme is no longer symptomatic relief which is variable butsurvival benefits and less need for cardiac transplantation and recurrent hospitalization.Saga of beta-blocker therapy taught us how mechanistic approach and experimental data do not always provide the correct answer to a complex pathophysiological syndrome.

Cost‐effective analysis by Markov Chains of open‐angle glaucoma therapy. Preliminary results

Acta Ophthalmologica ScandinavicaVolume 77, Issue S229 p. 56-57 Free Access Cost-effective analysis by Markov Chains of open-angle glaucoma therapy. Preliminary results C. M. Eandi, C. M. Eandi Physiopathology Clinic - Ophthalmology Section, Eye Clinic I, University of TurinSearch for more papers by this authorB. Brogliatti, B. Brogliatti Physiopathology Clinic - Ophthalmology Section, Eye Clinic I, University of TurinSearch for more papers by this authorM. P. Micieli, M. P. Micieli Physiopathology Clinic - Ophthalmology Section, Eye Clinic I, University of TurinSearch for more papers by this authorF. M. Grignolo, F. M. Grignolo Physiopathology Clinic - Ophthalmology Section, Eye Clinic I, University of TurinSearch for more papers by this author C. M. Eandi, C. M. Eandi Physiopathology Clinic - Ophthalmology Section, Eye Clinic I, University of TurinSearch for more papers by this authorB. Brogliatti, B. Brogliatti Physiopathology Clinic - Ophthalmology Section, Eye Clinic I, University of TurinSearch for more papers by this authorM. P. Micieli, M. P. Micieli Physiopathology Clinic - Ophthalmology Section, Eye Clinic I, University of TurinSearch for more papers by this authorF. M. Grignolo, F. M. Grignolo Physiopathology Clinic - Ophthalmology Section, Eye Clinic I, University of TurinSearch for more papers by this author First published: 13 November 2014 https://doi.org/10.1111/j.1600-0420.1999.tb01154.xCitations: 3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. References Kobelt G, Joensson L, Gerdtham U & Krieglstein GK (1998): Direct costs of glaucoma management following initiation of medical therapy. Graefe's Arch Clin Exp Ophthalmol 226: 811– 821. Kobelt-Nguyen G, Gerdtham U-G & Alm A (1998): Costs of treating primary open-angle glaucoma and ocular hypertension: a retrospective, observational two-year chart review of newly diagnosed patients in Sweden and the United States. J of Glaucoma 7; 95– 104. Stewart WC, Sine C, Cate E et al. (1997): Daily cost of beta-adrenergic blocker therapy. Arch Ophthalmol 115: 853– 856. Citing Literature Volume77, IssueS229December 1999Pages 56-57 ReferencesRelatedInformation

The Effect of Heart Rate Control on Myocardial Ischemia Among High-Risk Patients After Vascular Surgery

Patients undergoing vascular surgery have a high risk of suffering major postoperative cardiac events.Preoperative myocardial ischemia as detected by Holter monitoring identifies a high-risk subgroup whose postoperative ischemia, similarly detected, seems to herald major cardiac events. In this study, we determined whether systematic, patient-specific postoperative heart rate control with beta-adrenergic blocker therapy decreases the incidence of postoperative ischemia among high-risk vascular surgery patients. A total of 26 of 150 patients who underwent elective vascular surgery and were monitored preoperatively by 24-h Holter were found to have significant myocardial ischemia as defined by ST-segment depression. The minimal heart rate at which this ST-segment depression occurred was identified (ischemic threshold), and these 26 patients were then randomized to receive continuous IV beta-blockade with esmolol or placebo plus usual medical therapy, aiming to reduce the postoperative heart rate to 20% below the ischemic threshold. All patients were monitored by Holter for 48 h postoperatively. Postoperative Holter readings were analyzed for the incidence of ischemia and for the number of hours during which heart rate was controlled below the ischemia threshold. Patients had a median of two episodes of preoperative ischemia lasting a median of 30 min (range 1-155 min). A total of 15 patients were randomized to receive esmolol, and 11 were randomized to receive placebo. The two groups were comparable with respect to clinical characteristics and incidence and duration of preoperative ischemia. Ischemia persisted in the postoperative period in 8 of 11 placebo patients (73%), but only 5 of 15 esmolol patients (33%) (P < 0.05). Of the 15 esmolol patients, 9 had mean heart rates below the ischemic threshold, and all 9 had no postoperative ischemia. A total of 4 of 11 placebo patients had mean heart rates below the ischemic threshold, and 3 of the 4 had no postoperative ischemia. There were two postoperative cardiac events among patients who had postoperative ischemia (one placebo, one esmolol) and whose mean heart rates exceeded the ischemic threshold. Our data suggest that patient-specific, strict heart rate control aiming for a predefined target based on individual preoperative ischemic threshold was associated with a significant reduction and frequent elimination of postoperative myocardial ischemia among high-risk patients and provide a rationale for a larger trial to examine this strategy's effect on cardiac risk. Implications: Patients who undergo peripheral vascular surgery often experience transient cardiac complications and/or permanent heart damage just after surgery because of inadequate myocardial blood flow. In this study, we identified patients at high risk of cardiac complications after vascular surgery and showed that if their heart rate was carefully controlled for 48 h after surgery, myocardial ischemia, a common marker of heart injury, was markedly reduced. (Anesth Analg 1999;88:477-82)

Drug Therapy Before Coronary Artery Surgery

We conducted this study to evaluate whether there is an association between preoperative drug therapy and inhospital mortality in patients undergoing coronary artery graft surgery.We collected data on 1593 consecutive patients undergoing coronary artery surgery. The relative risk of in-hospital mortality was determined by logistic regression with in-hospital mortality as the dependent variable, and independent variables that included known risk factors and preoperative cardioactive or antithrombotic drug treatment, i.e., age; left ventricular function; left main coronary artery disease; urgent priority; gender; previous cardiac surgery; concurrent cardiovascular surgery; chronic lung disease; creatinine concentration; hemoglobin concentration; diabetes; hypertension; cerebrovascular disease; recent myocardial infarction; prior vascular surgery; number of arteries bypassed; and regular daily treatment with beta-blockers, aspirin within 5 days, calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, digoxin, or warfarin. In-hospital mortality was 3.3%. The relative risk of in-hospital mortality (with 95% confidence intervals of the relative risk) associated with the following drug treatments was: nitrates 3.8 (1.5-9.6), beta-blockers 0.4 (0.2-0.8), aspirin within 5 days 1.0 (0.5-1.9), calcium antagonists 1.1 (0.6-2.1), ACE inhibitors 0.8 (0.4-1.5), digoxin 0.7 (0.2-1.8), and warfarin 0.3 (0.1-1.6). We conclude that in-hospital mortality is positively associated with preoperative nitrate therapy and negatively associated with beta-adrenergic blocker therapy. A significant association between in-hospital mortality and the preoperative use of calcium antagonists, ACE inhibitors, aspirin, digoxin, and warfarin was not confirmed. Implications: We examined the association between common drug treatments for ischemic heart disease and short-term survival after cardiac surgery using a statistical method to adjust for patients' preoperative medical condition. Death after surgery was more likely after nitrate therapy and less likely after beta-blocker therapy. (Anesth Analg 1999;88:286-91)

Drug therapy before coronary artery surgery: nitrates are independent predictors of mortality and beta-adrenergic blockers predict survival.

We conducted this study to evaluate whether there is an association between preoperative drug therapy and in-hospital mortality in patients undergoing coronary artery graft surgery. We collected data on 1593 consecutive patients undergoing coronary artery surgery. The relative risk of in-hospital mortality was determined by logistic regression with in-hospital mortality as the dependent variable, and independent variables that included known risk factors and preoperative cardioactive or antithrombotic drug treatment, i.e., age; left ventricular function; left main coronary artery disease; urgent priority; gender; previous cardiac surgery; concurrent cardiovascular surgery; chronic lung disease; creatinine concentration; hemoglobin concentration; diabetes; hypertension; cerebrovascular disease; recent myocardial infarction; prior vascular surgery; number of arteries bypassed; and regular daily treatment with beta-blockers, aspirin within 5 days, calcium antagonists, angiotensin converting enzyme (ACE) inhibitors, digoxin, or warfarin. In-hospital mortality was 3.3%. The relative risk of in-hospital mortality (with 95% confidence intervals of the relative risk) associated with the following drug treatments was: nitrates 3.8 (1.5-9.6), beta-blockers 0.4 (0.2-0.8), aspirin within 5 days 1.0 (0.5-1.9), calcium antagonists 1.1 (0.6-2.1), ACE inhibitors 0.8 (0.4-1.5), digoxin 0.7 (0.2-1.8), and warfarin 0.3 (0.1-1.6). We conclude that in-hospital mortality is positively associated with preoperative nitrate therapy and negatively associated with beta-adrenergic blocker therapy. A significant association between in-hospital mortality and the preoperative use of calcium antagonists, ACE inhibitors, aspirin, digoxin, and warfarin was not confirmed. We examined the association between common drug treatments for ischemic heart disease and short-term survival after cardiac surgery using a statistical method to adjust for patients' preoperative medical condition. Death after surgery was more likely after nitrate therapy and less likely after beta-blocker therapy.

Effect of beta-adrenergic blocker therapy on the circadian rhythm of heart rate variability in patients with chronic stable angina pectoris

The circadian rhythm of heart rate variability is present in normal subjects and in patients with angina, with the greatest variation in the normal population and a smaller but significant variation in the anginal group. With beta-adrenergic blockade, significant improvement occurs in all daytime time domain parameters, nocturnal percentage of RR intervals with >50-ms variation, and square root of mean-squared differences of successive RR intervals, daytime total power, and high-frequency band, representing significant improvement in parasympathetic function.

Association of Retinal Capillary Perfusion with Visual Status during Chronic Glaucoma Therapy

Purpose: The purpose of the study is to determine whether retinal microcirculation is associated with the degree of visual function in glaucomatous eyes receiving chronic bilateral medical therapy with topical beta-blockers.Methods: A nonrandomized, 3-year prospective clinical study was undertaken on 37 patients with glaucoma and normal visual acuity receiving symmetric topical medication in both eyes. Humphrey 30-2, Henson CFA 2000, and Vistech 3 and 6 cycles/degree contrast sensitivity were obtained bilaterally at multiple visits, along with Oculix 1000 bluefield estimates of perimacular leukocyte velocity. The mean asymmetry of measurements obtained throughout the treatment period for each pair of eyes was determined, and correlations were obtained to assess visual function asymmetry against circulatory asymmetry.Results: Significant associations were observed between blue-field entoptic capillary leukocyte velocity measurements and those for all three visual function testing methods, the eye with the superior vision typically having the higher mean leukocyte velocity (P < 0.001 for both Humphrey mean deviation and Henson perimetry, P < 0.002 for Humphrey corrected pattern standard deviation, and P < 0.02 for contrast sensitivity at both 3 and 6 cycles/degree).Conclusions: Central retinal microcirculation is associated with various measures of central and peripheral visual function in glaucomatous eyes receiving beta-adrenergic blocker therapy.

A COMMONSENSE APPROACH TO VARICEAL BLEEDING

A cirrhotic patient with large varices and red color signs at endoscopy, and a portal pressure greater than 12 mmHg, has a high risk of bleeding from those varices in the near future. Prophylactic therapy with a nonselective beta-adrenergic blocking drug or long acting nitroglycerin reduces the risk of developing the first bleed and increases life expectancy. The acute variceal bleed requires prompt resuscitation with volume replacement, early initiation of vasoactive drugs (octreotide, somatosatin, or vasopressin plus nitroglycerin) to reduce portal pressure and decrease splanchnic flow, and early diagnostic endoscopy to determine the cause of bleeding. Variceal banding or sclerotherapy is successful in controlling the acute bleed in up to 90% of cases. Beta-adrenergic blocker therapy should be instituted once the bleed has been controlled and banding/sclerotherapy continued until the varices have been obliterated. In the patient with recalcitrant or recurrent bleeding, TIPS, selective shunt surgery, or liver transplantation may be options depending on the specifics of the particular case.