Initiation Of Beta-blocker Therapy Research Articles

Long-term clinical course of patients with catecholaminergic polymorphic ventricular tachycardia: A more than 10-year follow-up cohort study

ABSTRACT Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disorder characterized by ventricular arrhythmias induced by physical or emotional stress. Currently, there are limited data available on the long-term prognosis of CPVT. Methods and Results: In this study, which included both retrospective and prospective components, 12 patients with CPVT (7 males and 5 females) under 18 years old were enrolled to gather and evaluate demographic, clinical, and genetic data. The mean age at diagnosis onset was 7.0 ± 3.1 years. All patients experienced syncope. The mean follow-up duration was 20.1 years. During the follow-up period, all patients experienced at least one episode of supraventricular tachycardia (SVT). Despite beta-blocker therapy, nine patients experienced syncope (75%), and four patients were noncompliant with their treatment. An implantable cardiac defibrillator (ICD) implantation was performed in 10 patients (83%), and among those 5 (50%) experienced appropriate shocks. Inappropriate shocks were observed in all patients with an ICD. The left cardiac sympathetic denervation was performed in 6 patients (50%). One patient died during the follow-up period. Genetic testing was performed in eight patients, five of whom had RYR2 mutations, one patient had mutations in CASQ2, one in TECRL, and one was gene-elusive. Conclusions: The prevalence of cardiac events, even after the initiation of beta-blocker therapy, was found to be distressingly high during long-term follow-up. SVT, such as atrial fibrillation, were found to be more common than previously thought. Combination therapy with a beta-blocker and an IC antiarrhythmic drug shows promise. An individualized approach to the selection of treatment strategies is essential.

Incidental arrhythmias during atrial fibrillation screening in a hospital-based patient population

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Screening for atrial fibrillation may reveal other, incidental arrhythmias of relevance. We sought to describe such incidental arrhythmias in the prospective STARFIB cohort study, which screened for silent atrial fibrillation in hospitalized patients aged 65-84 years. Method Patients included in the STARFIB cohort study had up to three 7-day Holter ECGs, performed in two-month intervals. We analysed all the 7-day Holter ECGs of study participants for the presence of one of the following incidental arrhythmias: 1) sick-sinus-syndrome (SSS), defined as sinus arrest of ≥3 seconds duration; 2) second or higher degree atrioventricular block (AVB); 3) sustained atrial tachycardia of ≥30 seconds duration (AT); and 4) sustained ventricular tachycardia of ≥30 seconds duration (VT). Results A total of 2’077 Holter ECGs were performed in 794 patients (mean age 74.7 years; 49% females), resulting in a mean cumulative duration of an analyzable ECG signal of 414±136 hours per patient. We found incidental arrhythmias in 94 patients (11.8%). Among these were SSS in 14 patients (1.8%), AVB in 41 (5.2%), AT in 41 (5.2%), and VT in two (0.3%). The median pause duration in SSS was 4 seconds and SSS resulted in pacemaker implantation in one patient with a pause of 9 seconds duration. The most severe type of AVB found per patient was second degree AVB type Wenkebach in 23 patients (2.9%), second degree AVB type Mobitz or 2:1 AV conduction in 10 patients (1.3%) and complete AVB in 8 (1%; maximum pause 18 seconds). AVB led to pacemaker implantation in 9 patients (1.1%). The median duration and heart rate of AT was 2.2 minutes and 144 bpm, respectively. Initiation of betablocker therapy was recommended in 3 patients (0.4%) due to symptomatic AT. The duration and heart rate of VT was 3 minutes at 216 bpm in one patient and 38 seconds at 150 bpm in another. The former patient with VT experienced syncope and an ICD was implanted, whereas in the latter the betablocker dose was increased. One patient died from a non-cardiac cause during a Holter ECG, which showed progressive bradycardia and finally asystole. Conclusion Incidental arrhythmias were frequently discovered during screening for atrial fibrillation and resulted in device therapy in 1.4% of our cohort patients.

Autonomic influences related to frequent ventricular premature beats in patients without structural heart disease.

To study the possible role of autonomic influences on the occurrence of frequent premature ventricular beats (VPBs) in subjects without structural heart disease.24-hour Holter ECG recordings (≥1500 VPBs/d, sinus rhythm) of 20 symptomatic patients (9 women, 11 men, mean age 58.9 years) without structural heart disease were used for the study. The circadian distribution pattern of VPBs was studied (paired t test) by dividing the day into 3 periods (16:00–22:00–06:00–16:00), and correlations were analyzed between the absolute (ln transformed) and relative (% of total beats) average hourly numbers of VPBs and the hourly mean values of global and vagal time domain parameters of heart rate variability (Pearson correlation).No significant (P > .3 for every comparison) tendency for circadian distribution of VPBs was found. However, VPBs showed a significant correlation with rMSSD (r = 0.51 and P = .02 for the relative number), which became even stronger if VPBs were > 8000/d (r = 0.65 and P = .04 for both numbers).The significant correlation between the number of VPBs and a vagally mediated parameter underlines the triggering/permitting effect of parasympathetic tone on ventricular ectopy. This fact suggests that initiation of beta-blocker therapy could not be recommended routinely in these patients.

Is cardiovascular evaluation necessary prior to and during beta-blocker therapy for infantile hemangiomas?: A cohort study

Although consensus guidelines for pretreatment evaluation and monitoring of propranolol therapy in patients with infantile hemangiomas (IH) have been formulated, little is known about the cardiovascular side effects. We sought to analyze cardiovascular evaluations in patients with IH at baseline and during treatment with an oral beta-blocker. Data from 109 patients with IH were retrospectively analyzed. Patient and family history, pretreatment electrocardiogram (ECG), heart rate, and blood pressure were evaluated before initiation of beta-blocker therapy. Blood pressure and standardized questionnaires addressing side effects were evaluated during treatment. Questionnaire analyses (n = 83) identified 3 cases with a family history of cardiovascular disease in first-degree relatives. ECG findings were normal in each case and no serious complication of therapy occurred. ECG abnormalities were found in 6.5% of patients but there were no contraindications to beta-blocker therapy and no major complications. Hypotension in 9 patients did not require therapy adjustment. In all, 88 parents (81%) reported side effects during beta-blocker treatment. The relatively small patient cohort is a limitation. Pretreatment ECG is of limited value for patients with an unremarkable cardiovascular history and a normal heart rate and blood pressure. Hypotension may occur during treatment.

Does Acute Hemodynamic Response to Carvedilol in Hepatic Venous Pressure Gradient Predicts Morbidity and Mortality in Cirrhosis? Prospective Study

Background: Portal hypertension leads to most of the complication of cirrhosis: both bleeding and non-bleeding. Most complications due to portal hypertension can be ameliorated by β-blockers in those who are hemodynamic responders. To identify hemodynamic responder, a repeat hepatic venous pressure gradient (HVPG) is required 4–6 weeks after initiation of beta-blocker therapy. Acute hemodynamic response is a recent modality of determining HVPG response immediately during the baseline HVPG by giving high dose of injectable or oral beta-blocker. Aims: To assess the acute effect of Carvedilol on HVPG and its impact on outcome in cirrhotics over a 6-month period of follow up. Patients and Methods: Patients requiring β-blocker therapy, for primary (25/69) or secondary (44/69) prevention of variceal bleeding, were subjected to HVPG measurement. Acute Responder were defined as HVPG <12 mmHg or >10% fall in HVPG from baseline. Immediately after HVPG they were given Tab. Carvedilol 25 mg and a repeat HVPG was performed after one hour. On the basis of hemodynamic response 2 groups were made, Acute responders and non-responders. Both these groups were followed for 6 months. A repeat HVPG was done in acute responder group after 6 month. Both these group of patients were offered standard medical therapy with beta-blocker (Carvedilol) and regular EVL. All complications, hospitalization and outcome of patient noted at the end of 6 month. Results: Out of 69 patients, 49 (71%) patients showed acute reduction in HVPG of >10% after oral Carvedilol. There were no baseline differences between the two groups. On follow-up, complications like ascites was significantly less common in acute responder group as compared to non-responder group (P < 0.001). However, there was no statistically significant difference in mortality between acute responder and non-responder groups (P > 0.05). Repeat HVPG after a median period of 6 months could be performed in 41 of 49 patients in the acute responder group, while 2 patients was not willing for a repeat HVPG and 6 patients had died during this period. Out of 41 patients 35 (85%) patients were still responders (long term responders) and 6 (15%) patient were non long term responders. Conclusions: Determination of acute response to carvedilol is not only a convenient and rapid way to identify beta-blocker hemodynamic responders; it also is an excellent prognostic marker as acute responders develop less portal hypertensive complication like ascites than non-responders on beta-blocker therapy. Also the most of acute responders are found to be longstanding responder. Keywords: HVPG; portal hypertension; cirrhosis; esophageal varices

Heart rate distribution and predictors of resting heart rate after initiation of beta-blocker treatment in patients with coronary artery disease: REsults of Sympathetic Evaluation And Research of China (RESEARCH) study

Background The importance of heart rate as secondary prevention strategies for patients with coronary artery disease (CAD) is emphasized by multiple guidelines. However, limited information is available on the heart rate distribution and the change patterns of resting heart rate when initiating beta-blocker therapy among Chinese patients with CAD. Methods The REsults of Sympathetic Evaluation And Research of China (RESEARCH) study is a multi-centre, prospective, observational study involving 147 centers in 23 cities across China. All eligible beta-blocker naive patients were prescribed with metroprolol succinate. Initial dosage and target heart rate were selected at the discretion of their physicians in charge according to their usual institutional practice. The heart rate distribution and the change patterns of resting heart rate after initiation of beta-blocker therapy were observed. Results The majority of patients (63.6%) were prescribed with 47.5 mg metroprolol succinate. At baseline, there were only 17.4% of patients whose heart rate was less than 70 beats per minute, and the proportion reached 42.5% and 79.1%, one month and two months after initiation of beta-blockers, respectively. Multivariate linear regression analysis showed that baseline heart rate (B=0.900, SE=0.006, t=141.787, P&lt;0.0001) and the dosage (B=-0.007, SE=0.002, t=-3.242, P=0.001) were independent predictors of resting heart rate 2 months after beta-blocker therapy. Conclusions Resting heart rate is not optimally controlled in a broadly representative cohort of Chinese outpatients with CAD even after initiation of β-blocker therapy, and baseline heart rate and the dosage of beta-blocker are both independent predictors of resting heart rate after β-blocker therapy.

Abstract 17678: The Correlation Between Collagen Degradation and LV Function Following Induction of Beta-Blocker Therapy

Objectives: Beta-blocker therapy inhibits LV remodeling, and improves not only LV systolic function but also LV diastolic function, and improves prognosis of heart failure patients. But it is unknown why beta-blocker therapy improves LV function. Recently, serum collagen markers such as Procollagen type I C-terminal propeptide (PICP) and collagen type I C-terminal telopeptide (CITP), are useful as index of myocardium collagen synthesis and degradation. We investigate correlation between collagen turnover and LV function following induction of beta-blocker therapy with systolic heart failure patients. Methods: Study population consisted of 46 patients with systolic heart failure. Patients were clinically stable within 1 month and on stable medical therapy, including ACEI or ARB and diuretics, and no beta-blocker therapy. We started beta-blocker therapy, initiated at a target dose of from 5 to 10mg/day. Echocardiography was performed before, 2, 6, and 12 months after the initiation of beta-blocker therapy. LV systolic function was estimated using the LV ejection fraction by Simpson biplane method. Peak systolic strain in the radial direction was measured at the anterior and posterior walls in the short-axis view. We measured E- and A-wave peak velocities and deceleration time (DcT) form the mitral inflow profile, and tissue Doppler early diastolic mitral annular velocity (E'). Serum PICP and CITP were determined. Results (table): A total of 46 patients were enrolled. The median age of all patients was 56±14 years. 15 patients were women and 31 patients were men. EF, DcT and E' were improved after induction of beta-blocker therapy. PICP was not changed, but CITP was decreased from 8.9±7.8 to 6.1±1.7ng/ml at 12 months after treatment. The lower %changes in CITP was associated with the higher %changes in DcT (r=0.21, p&lt;0.05), EF (r=0.29, p&lt;0.01) and radial systolic strain (r=0.26, p&lt;0.05), but not E'. The %changes in PICP were not related %changes in DcT and E'. Conclusions: The improvement in LV systolic function as indexes in EF and radial systolic strain and LV diastolic stiffness as indexes in DcT, correlated with inhibition of collagen degradation in patients with LV systolic function.

Key role of the molecular autopsy in sudden unexpected death

Sudden Cardiac Death (SCD) is a major and tragic complication of a number of cardiovascular diseases. While in the older populations, SCD is most frequently caused by underlying coronary artery disease and heart failure, in those aged under 40 years, the causes of SCD commonly include genetic disorders, such as inherited cardiomyopathies and primary arrhythmogenic diseases. As part of the evaluation of families in which SCD has occurred, the role of genetic testing has evolved as an important feature in both establishing an underlying diagnosis and in screening at-risk family relatives. Specifically, in cases where no definitive cause is identified at postmortem, i.e. Sudden Unexpected Death (SUD), the "molecular autopsy" has emerged as a key process in the investigation of the cause of death. The combination of clinical and genetic evaluation of families in which SUD has occurred provides a platform for early initiation of therapeutic and prevention strategies, with the ultimate goal to reduce sudden death among the young in our communities.

Risk of Fatal Arrhythmic Events in Long QT Syndrome Patients After Syncope

The aim of this study was to identify risk factors for fatal arrhythmias in long QT syndrome (LQTS) patients presenting with syncope. Syncope is highly predictive for future fatal arrhythmias in the LQTS. However, there are no data regarding risk stratification and management strategies in the high-risk subset of LQTS patients presenting with syncope. A total of 1,059 LQTS patients with a corrected QT interval > or =450 ms presenting with syncope as a first symptom were drawn from the International LQTS Registry. Cox proportional hazards regression was used to identify risk factors for a severe arrhythmic events comprising aborted cardiac arrest, appropriate implantable cardioverter-defibrillator therapy, and sudden cardiac death. The lowest risk was found in patients with only 1 syncopal episode occurring before the start of beta-blocker therapy. In contrast, patients experiencing syncope after starting beta-blocker therapy had a 3.6-fold increase in the risk of severe arrhythmic events (p < 0.001) relative to this low-risk group and displayed a risk of severe arrhythmic events similar to that of patients not treated with beta-blockers. Multiple syncopal episodes occurring before initiation of beta-blocker therapy were associated with an intermediate risk (hazard ratio: 1.8, p < 0.001). The risk of syncope during beta-blocker therapy is high during childhood in both sexes but is higher in women than in men (hazard ratio: 2.3, p < 0.001). Patients with syncope during beta-blocker therapy are at high risk of life-threatening events, and implantable cardioverter-defibrillator therapy should be considered in these patients. The risk of beta-blocker failure is highest in young children and in women.

High prevalence of exercise-induced arrhythmias in catecholaminergic polymorphic ventricular tachycardia mutation-positive family members diagnosed by cascade genetic screening

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease predisposing to life-threatening arrhythmias. We aimed to determine the prevalence of arrhythmias and efficacy of beta-blocker treatment in mutation-positive family members diagnosed by cascade genetic screening. Relatives of six unrelated CPVT patients were tested for the relevant mutation in the ryanodine receptor-2 gene. Mutation carriers underwent an exercise test at inclusion time and 3 months after the initiation of beta-blocker therapy in the highest tolerable dose. The occurrence of ventricular premature beats, couplets, and non-sustained ventricular arrhythmias (nsVT) were recorded in addition to the heart rate at which they occurred. Thirty family members were mutation carriers and were followed for 22 (13-288) months. Previous undiagnosed CPVT-related symptoms were reported by eight subjects. Exercise test induced ventricular arrhythmias in 23 of the 30 mutation carriers. On beta-blocker treatment, exercise-induced arrhythmias occurred at a lower heart rate (117 +/- 17 vs. 135 +/- 34 beats/min, P = 0.02) but at similar workload (P = 0.78). Beta-blocker treatment suppressed the occurrence of exercise-induced nsVT in three of the four patients, while less severe arrhythmias were unchanged. One patient died during follow-up. Exercise test revealed a high prevalence of arrhythmias in CPVT mutation carriers diagnosed by cascade genetic screening. beta-Blocker therapy appeared to suppress the most severe exercise-induced arrhythmias, while less severe arrhythmias occurred at a lower heart rate.

Clinical Effectiveness of Beta-Blockers in Heart Failure: Findings From the OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure) Registry

We sought to examine associations between initiation of beta-blocker therapy and outcomes among elderly patients hospitalized for heart failure. Beta-blockers are guideline-recommended therapy for heart failure, but their clinical effectiveness is not well understood, especially in elderly patients. We merged Medicare claims data with OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure) records to examine long-term outcomes of eligible patients newly initiated on beta-blocker therapy. We used inverse probability-weighted Cox proportional hazards models to determine the relationships among treatment and mortality, rehospitalization, and a combined mortality-rehospitalization end point. Observed 1-year mortality was 33%, and all-cause rehospitalization was 64%. Among 7,154 patients hospitalized with heart failure and eligible for beta-blockers, 3,421 (49%) were newly initiated on beta-blocker therapy. Among patients with left ventricular systolic dysfunction (LVSD) (n = 3,001), beta-blockers were associated with adjusted hazard ratios of 0.77 (95% confidence interval [CI]: 0.68 to 0.87) for mortality, 0.89 (95% CI: 0.80 to 0.99) for rehospitalization, and 0.87 (95% CI: 0.79 to 0.96) for mortality-rehospitalization. Among patients with preserved systolic function (n = 4,153), beta-blockers were associated with adjusted hazard ratios of 0.94 (95% CI: 0.84 to 1.07) for mortality, 0.98 (95% CI: 0.90 to 1.06) for rehospitalization, and 0.98 (95% CI: 0.91 to 1.06) for mortality-rehospitalization. In elderly patients hospitalized with heart failure and LVSD, incident beta-blocker use was clinically effective and independently associated with lower risks of death and rehospitalization. Patients with preserved systolic function had poor outcomes, and beta-blockers did not significantly influence the mortality and rehospitalization risks for these patients.

Post–myocardial infarction β-blocker therapy: The bradycardia conundrum. Rationale and design for the Pacemaker & β-blocker therapy post-MI (PACE-MI) trial

Multiple clinical trials have demonstrated beta-blockers improving survival after myocardial infarction (MI). Patients with "bradycardia-related" contraindications to beta-blockers, such as those with asymptomatic bradycardia or AV conduction abnormalities, have been excluded from clinical trials of beta-blockers and continue to be excluded from post-MI beta-blocker therapy in routine clinical practice. These patients tend to be elderly and have a high 1-year mortality. If beta-blockers provide benefit to the post-MI patient independent of their heart rate-lowering effect, then these patients could benefit substantially from initiation of beta-blocker therapy. However, in this particular group of patients, beta-blockers can be safely initiated only if more severe or significant bradycardia can be prevented by pacemaker implantation. It is unclear whether adverse effects related to pacemaker implantation could also negate some or all of the hypothesized benefit of beta-blocker therapy. Although beta-blockers are particularly effective in the elderly, the benefit of beta-blocker therapy in patients with bradycardia-related contraindications to beta-blockers has not been established. The PACE-MI trial is a randomized controlled trial that will address whether beta-blocker therapy enabled by pacemaker implantation is superior to no beta-blocker and no pacemaker therapy after MI in patients with rhythm contraindications to beta-blockers or in those who have developed symptomatic bradycardia due to beta-blockers. The trial will randomize 1124 patients to standard therapy (not to include beta-blockers as patients must have a contraindication to be enrolled) or standard therapy plus pacemaker implantation and beta-blocker. The primary end point is the composite end point of total mortality plus nonfatal reinfarction.

Early Initiation of β Blockade in Heart Failure: Issues and Evidence

Despite clinical trials demonstrating that inhibitors of the renin-angiotensin and sympathetic nervous systems can reduce the mortality and morbidity risk associated with heart failure, these drugs have remained underutilized in general clinical practice. In particular, many patients with heart failure due to left ventricular systolic dysfunction fail to receive beta blockers, although this class of drugs, as well as other antihypertensive agents such as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, are recommended as part of routine heart failure therapy by national expert consensus guidelines. In-hospital initiation of beta-blocker therapy may improve long-term utilization by physicians and compliance by patients through obviating many of the misperceived dangers associated with beta blockade. The following review of the clinical trial data from the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) trial, the Metoprolol Controlled-Release Randomized Intervention Trial in Heart Failure (MERIT-HF), the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial, and the Initiation Management Predischarge Process for Assessment of Carvedilol Therapy for Heart Failure (IMPACT-HF) trial on the efficacy, safety, and tolerability of beta blockers indicates that early initiation can be safely achieved and can improve patient outcomes.

The effect of beta blocker use on cyclosporine level in cardiac transplant recipients

Background: Beta blockers are frequently used after cardiac transplantation for their favorable effects on blood pressure control. There is no well-known interaction between beta blockers and cyclosporine (CsA). The aim of this study is to evaluate the effects of the commonly used beta blockers carvedilol and metoprolol on CsA level when initiated in cardiac transplant recipients. Methods: Using the cardiac transplant database at our center, we identified patients who were started on either carvedilol or metoprolol for blood pressure control. We then compared their CsA doses and levels before and within one to two weeks after the initiation of beta blocker therapy. Comparisons were also made between carvedilol and metoprolol groups. Results: In our transplant population, we found 20 patients on metoprolol, and 12 patients on carvedilol. With initiation of metoprolol, CsA level decreased in 12 patients and increased in 8 patients. The mean CsA level before and after metoprolol initiation was 236 and 253 ng/ml, respectively (p=0.50). In an attempt to maintain a therapeutic CsA level, the mean CsA dose was not significantly adjusted (from a mean of 293 mg/day to a mean of 294 mg/day; p=0.92). In the carvedilol group, CsA level increased in 10 of 12 patients. The mean CsA level before the initiation of carvedilol was 257 ng/ml. The mean CsA level after carvedilol initiation was 380 ng/ml (p=0.009). In an attempt to maintain a therapeutic CsA level, the mean CsA dose was reduced by 10% from a mean of 319 mg/day to a mean of 288 mg/day (p=0.004). Conclusion: Carvedilol, but not metoprolol, was associated with a significant increase in CsA levels after initiation in cardiac transplant recipients. An average reduction of 10% is necessary on the CsA dose upon initiation of carvedilol, and close follow up on the level is essential.

Effects of long-term beta-blocker therapy on P-wave duration and dispersion in patients with rheumatic mitral stenosis

Background P-wave dispersion (PWD), has been defined as the difference between maximum and minimum P-wave duration. Prolonged P-wave duration and increased PWD have been reported to be related with increased risk for atrial fibrillation (AF). AF is the most common sustained arrhythmia encountered in patients with rheumatic mitral stenosis (MS). Beta-blockers are the mainstay of therapy in patients with rheumatic MS to control ventricular rate both during sinus rhythm and AF. In the present study, we aimed to evaluate the effect of long-term beta-blocker therapy on P-wave duration and PWD in patients with rheumatic MS. Method Study population includes 46 patients (group I, 8 men, 38 women, mean age=34±8 years) with newly diagnosed moderate-to-severe rheumatic MS who have not taken any medication before and prescribed oral beta-blocker therapy and 46 healthy control subjects without any cardiovascular disease (group II, 8 men, 38 women, mean age=35±7 years). Mitral valve area, maximum and mean diastolic mitral gradients, left atrial diameter, and systolic pulmonary artery pressure were evaluated by transthoracic echocardiography before initiation of beta blocker therapy and repeated at the end of the first month. Baseline maximum and minimum P-wave duration and PWD were determined on 12-lead electrocardiogram recorded for each patient and control subject and repeated at the end of the first month after initiation of beta-blocker therapy in patient group. Results Maximum P-wave duration and PWD were found to be significantly higher in patients with MS than those in control subjects (Maximum P-wave duration: 128±7 ms vs. 104±4 ms and PWD: 52±6 ms vs. 27±3 ms, p<0.001 for both). Both groups had comparable minimum P-wave duration (75±4 ms vs. 76±4 ms, p=0.093). Maximum P-wave duration and PWD were found to be significantly decreased by long-term beta blocker therapy (Maximum P-wave duration; 128±7 ms vs. 122±6 ms, p<0.001, PWD; 52±6 ms vs. 47±5 ms, p<0.001). However, there was no significant difference between the values of minimum P wave duration measured before and at the end of the first month of beta-blocker therapy (75±4 ms vs. 75±3 ms, p=0.678). Statistically significant decrease were detected on maximum and mean mitral gradient and systolic pulmonary artery pressure and resting heart rate at the end of the first month of beta-blocker therapy. However, only the change in resting heart rate was found to be significantly correlated with the decrease in maximum P-wave duration and PWD (Maximum P-wave duration: r=0.327, p=0.026, PWD: r=0.378, p=0.01). Conclusion We have shown for the first time that long-term beta-blocker therapy causes a significant decrease in maximum P-wave duration and PWD in patients with rheumatic MS.

Hepatic venous pressure gradient measurements to assess response to primary prophylaxis in patients with cirrhosis: a decision analytical study.

The measurement of the hepatic venous pressure gradient may identify a suboptimal response to beta-blockers in patients with varices at risk for bleeding. However, the cost-effectiveness of routine hepatic venous pressure gradient measurements to guide primary prophylaxis has not been examined. We used decision analysis to evaluate two hepatic venous pressure gradient measurement strategies relative to standard beta-blocker therapy in a hypothetical cohort of patients with high-risk varices: (i) hepatic venous pressure gradient measurement 4 weeks after the initiation of beta-blocker therapy; and (ii) hepatic venous pressure gradient measurement prior to and 4 weeks after the initiation of beta-blocker therapy. The total expected costs, variceal bleeding episodes and deaths were calculated over a 1-year time horizon. Beta-blocker therapy was associated with total costs of $1464, seven variceal bleeding episodes, one variceal bleeding episode-related death and 15 deaths. One hepatic venous pressure gradient measurement was associated with total costs of $5015, four variceal bleeding episodes, one variceal bleeding episode-related death and 15 deaths. Two hepatic venous pressure gradient measurements were associated with total costs of $8657, four episodes of variceal bleeding, one variceal bleeding episode-related death and 15 deaths. Compared with beta-blocker therapy alone, the incremental costs per variceal bleeding episode prevented and death averted were, respectively, $108 185 and $355 100 (one hepatic venous pressure gradient measurement) and $202 796 and $719 300 (two hepatic venous pressure gradient measurements). The results were sensitive to the time horizon of the analysis, the probability of bleeding whilst on beta-blockers and the cost of hepatic venous pressure gradient measurement. Hepatic venous pressure gradient measurement to guide primary prophylaxis is an expensive strategy for reducing variceal bleeding or death, especially in patients with limited life expectancy, such as those with advanced, decompensated cirrhosis.

Does acute-phase beta blockade reduce left atrial appendage function in patients with chronic nonvalvular atrial fibrillation?

To investigate whether acute-phase beta-blocker therapy has a harmful effect on left atrial appendage (LAA) function in patients with chronic nonvalvular atrial fibrillation by transesophageal echocardiography (TEE), we evaluated 21 patients with normal left ventricular systolic function and a poorly controlled ventricular rate, despite the use of digoxin. Baseline parameters that were obtained included heart rate, blood pressure, LAA emptying velocities, and left atrial spontaneous echo contrast intensity. Then, each patient was given a bolus dose of 5 mg metoprolol. Ten minutes later, a second set of assessments was performed. After the first TEE studies, each patient began treatment with metoprolol (50 mg orally twice daily for 1 week). A second TEE study was performed after 1 week of continuous oral metoprolol therapy at maintenance dose, and values were again determined. The average resting apical heart rate was 91 ± 7 bpm. As expected, beta-blocker therapy showed a marked decrease in heart rate at 10 minutes (79 ± 6 bpm, P <.001) and at 1 week (71 ± 4 bpm, P <.001). Beta-blocker therapy caused a significant reduction in systolic and diastolic blood pressures (144 ± 16 / 93 ± 6 mm Hg at baseline, 137 ± 16 / 87 ± 9 mm Hg at 10 minutes, and 135 ± 12 / 86 ± 8 mm Hg at 1 week, P <.001). With the beta-blocker therapy, the baseline transesophageal Doppler parameter of LAA emptying velocities (at baseline 24 ± 7 cm/s) fell significantly at 10 minutes (19 ± 7 cm/s, P <.001) and at 1 week (17 ± 6 cm/s, P <.001) after initiation of beta-blocker therapy. After a bolus of metoprolol, spontaneous echo contrast intensity did not change in any patients, but 1 week later, it increased in 1 patient. In 2 patients who had not been found to have an LAA thrombus at baseline TEE study, the second TEE examination demonstrated new thrombi in the LAA. In conclusion, our findings suggest that in patients with chronic nonvalvular atrial fibrillation who have normal left ventricular systolic function and a poorly controlled ventricular rate despite the use of digoxin, acute-phase beta blockade may have a harmful effect on LAA function. (J Am Soc Echocardiogr 2001;14:194-9.)

Effect of beta-blockers on circulating levels of inflammatory and anti-inflammatory cytokines in patients with dilated cardiomyopathy

OBJECTIVESThis study was designed to evaluate the beneficial effect of beta-blockers on circulating cytokine levels in patients with dilated cardiomyopathy (DCM).BACKGROUNDElevated circulating levels of inflammatory cytokines have been reported in patients with DCM. However, alterations of the levels of inflammatory and anti-inflammatory cytokines in association with beta-blocker therapy are unknown.METHODSWe studied 32 patients with idiopathic DCM who had been treated with digitalis, diuretics and angiotensin-converting enzyme inhibitors. In addition to this combination therapy, beta-blockers were started in all patients. Serum levels of interleukin (IL)-10, tumor necrosis factor-alpha (TNF-alpha) and soluble TNF receptors (sTNF-R1 and R2) were measured at baseline and 12 weeks after the initiation of beta-blocker therapy. We also measured plasma levels of neurohumoral factors, as well as left ventricular (LV) size and function. Ten age-matched subjects with no cardiac disease served as the control group.RESULTSBaseline levels of IL-10, TNF-alpha and sTNF-R2 were significantly higher in patients with DCM than in control subjects (p < 0.05). There was a significant positive correlation between IL-10 and TNF-alpha levels (r = 0.545, p = 0.029). The TNF-alpha/IL-10 ratio correlated well with plasma epinephrine levels (r = 0.677, p = 0.025), and the level of sTNF-R2 was closely related to LV size. Serum levels of IL-10, TNF-alpha and sTNF-R2 were significantly decreased during beta-blocker therapy (p < 0.005).CONCLUSIONSOur findings indicate that beta-blockers have an important immunoregulatory role in modifying the dysregulated cytokine network in DCM. This effect of beta-blockers may be partly responsible for the efficacy of therapeutic drugs for heart failure.

The rational use of beta-adrenoceptor blockers in the treatment of heart failure. The changing face of an old therapy.

Heart failure is one of the commonest debilitating conditions of industrialized society, with mortality and morbidity comparable with that of the common neoplastic diseases. The role of antagonists of the adrenergic beta-receptor (beta-blockers) in heart failure has been the subject of debate for many years. Data from studies of the therapeutic use of beta-blockers in patients following acute myocardial infarction suggest that in this circumstance these agents confer at least as much benefit to patients with heart failure as they do to those without. Similarly retrospective analysis of a number of the studies of angiotensin converting enzyme (ACE) inhibitors in heart failure suggest a greater effect of the combination of beta-blocker with ACE inhibitor compared with ACE inhibitor alone. The results of recent prospective, placebo-controlled studies of the addition of beta-blocker to standard therapy in patients with chronic heart failure have confirmed a significant beneficial effect. beta-blocker therapy in these studies was well tolerated and in addition to improved mortality, beta-blocker therapy is associated with improved morbidity in terms of progressive heart failure and numbers of hospitalizations. Initiation of beta-blocker therapy in heart failure may be associated with deterioration of cardiac function in the short term. Treatment should be started at a low dose of beta-blocker with slow up-titration in a number of steps over several weeks. In spite of the established benefits of ACE inhibition in patients with heart failure, this treatment is under-utilized. Part of this shortfall is due to physicians' perceptions regarding potential unwanted effects of ACE inhibition. Perceptions regarding unwanted effects of beta-adrenoceptor blocker therapy are likely to be at least as great. While beta-blockade represents a welcome addition to the therapeutic armoury of physicians caring for patients with heart failure, initiation and stabilization of beta-adrenoceptor blocker therapy should be undertaken under specialist supervision.

National use and effectiveness of beta-blockers for the treatment of elderly patients after acute myocardial infarction: National Cooperative Cardiovascular Project.

Despite the importance of beta-blockers for secondary prevention after acute myocardial infarction (AMI), several studies have suggested that they are substantially underutilized, particularly in older patients. To describe the contemporary national pattern of beta-blocker prescription at hospital discharge among patients aged 65 years or older with an AMI, to identify the most important predictors of the prescribed use of beta-blockers at discharge, and to determine the independent association between beta-blockers at discharge and mortality in clinical practice. Retrospective cohort study using data created from medical charts and administrative files. Acute care nongovernmental hospitals in the United States. National cohort of 115015 eligible patients aged 65 years or older who survived hospitalization with a confirmed AMI in 1994 or 1995. Blocker as a discharge medication and mortality in the year after discharge. Among the 45308 patients without contraindications to beta-blockers, 22665 (50.0%) had a beta-blocker as a discharge medication. There was significant variation by state, ranging from 30.3% to 77.1 %. Of the 36795 patients who were not receiving beta-blocker therapy on admission, 16006 (43.5%) had therapy initiated on or before discharge. Demographic and clinical variables explained relatively little of the variation in the initiation of beta-blocker therapy. The prescribed use of calcium channel blockers at discharge had a strong negative association with the use of beta-blockers (odds ratio [OR] of beta-blocker use, 0.25; 95% confidence interval [CI], 0.24-0.26). The New England region had significantly higher use of beta-blocker therapy than the rest of the country. Compared with cardiologists, internists had similar rates (OR, 0.94; 95% CI, 0.90-1.00) and general and family practice physicians had lower rates (OR, 0.78; 95% CI, 0.73-0.83). After adjusting for potential confounders, beta-blockers were associated with a 14% lower risk of mortality at 1 year after discharge. The association with lower mortality was present in subgroups stratified by age, sex, and left ventricular ejection fraction. Many ideal patients for beta-blocker therapy are not prescribed these drugs at discharge following AMI. The clinical and demographic characteristics of the patients do not explain much of the variation in the treatment pattern. Geographic factors and physician specialty are independently associated with the decision to use beta-blockers. Elderly patients who are prescribed beta-blockers at discharge have a better survival rate, consistent with the findings of randomized controlled trials of younger and lower-risk populations.