Current utilization trends for beta-blockers in cardiovascular disease.

Beta blockers have repeatedly demonstrated their therapeutic value in the treatment of a variety of diseases; as a result, multiple treatment guidelines advocate the use of beta blockers. Despite these guidelines, the use of beta blockers is remarkably low. Numerous factors that influence the trends of drug use include pharmaceutical advertisements, physician legal concerns, marketing influences, outdated therapeutic contraindications, and patient and physician demographics. Recent primary evidence from randomized clinical trials has demonstrated a significant benefit to patients with heart failure when beta-blocker therapy is added to standard therapy. To ensure proper treatment, continuing efforts must be made to provide patients with appropriate therapy that is proven to reduce the risks of mortality and morbidity.

Metoprolol CR/XL in patients with heart failure: A pilot study examining the tolerability, safety, and effect on left ventricular ejection fraction.

BACKGROUND: This study was designed to investigate the tolerability, safety, and effect on left ventricular function of a new long-acting preparation of metoprolol, metoprolol succinate (CR/XL). METHODS AND RESULTS: Sixty patients were randomly assigned with a 2:1 ratio, drug versus placebo, administered with a gradually increasing dose of 12.5 to 150 mg of blinded medication during an 8-week period and continued for 6 months. The average peak dose achieved was 99 mg and 132 mg in the metoprolol succinate and placebo groups, respectively. The drug was well tolerated and there was no significant difference in drug withdrawals, New York Heart Association class, or quality of life assessment. The increase in left ventricular ejection fraction measure at baseline and 6 months measured by radioisotopic ventriculography was greater in the metoprolol succinate group (27. 5% to 36.3%) than in the placebo group (26% to 27.9%) (P <.015). Examination of serial Holter electrocardiographic recordings indicate that metoprolol succinate therapy was associated with a significant (P <.05) decrease in total ventricular ectopy at 8 weeks of therapy and a decrease in ventricular couplets and nonsustained ventricular tachycardia at 8 through 26 weeks of therapy. No changes were observed in plasma norepinephrine during therapy except a transitory significant (P <.05) increase in N terminal proatrial natriuretic factor at 8 weeks in the metoprolol succinate group. CONCLUSIONS: This study indicates that treatment with metoprolol succinate for a 6-month period is safe and well tolerated and is associated with an increase in left ventricular ejection fraction and a decrease in ventricular ectopic beats.

Effect of selective versus nonselective beta blockade on QT dispersion in patients with nonischemic dilated cardiomyopathy.

We retrospectively examined the electrocardiograms in all of our patients with nonischemic dilated cardiomyopathy and normal sinus rhythm before and after at least 3 months of metoprolol (n = 12), bucindolol (n = 8), carvedilol (n = 6), or no beta blocker (n = 9). Both beta1-selective and nonselective beta-adrenergic blockade reduced QTc dispersion equally in patients with dilated cardiomyopathy.

The importance of randomized clinical trials and evidence-based medicine: a clinician's perspective.

Clinical evaluation of therapies for patient care has evolved during the twentieth century from a variety of scientific methods. As a result of medical, political, and economic changes that occurred in the 1990s, randomized clinical trials and evidence-based methods are presently in the forefront of the physician's thinking in the decision-making process for therapeutic interventions. A new standard of patient care has emerged during this process. This report provides clinician's viewpoint of the importance and interpretation of evidence-based methods and suggests a strategy when such evidence does not exist.

The importance of randomized clinical trials and evidence-based medicine: a clinician's perspective.

Clinical evaluation of therapies for patient care has evolved during the twentieth century from a variety of scientific methods. As a result of medical, political, and economic changes that occurred in the 1990s, randomized clinical trials and evidence-based methods are presently in the forefront of the physician's thinking in the decision-making process for therapeutic interventions. A new standard of patient care has emerged during this process. This report provides a clinician's viewpoint of the importance and interpretation of evidence-based methods and suggests a strategy when such evidence does not exist.

Beta blockade, ventricular arrhythmias, and sudden cardiac death.

The mechanisms precipitating sudden cardiac death may be ischemic, electrical, or mechanical. Activation of the autonomic nervous system leads to an increase in sympathetic tone, increasing blood pressure, shear forces, heart rate, platelet aggregation, and blood viscosity while decreasing heart-rate variability and lowering the ventricular fibrillation threshold. Such changes increase the likelihood of plaque rupture or erosion and platelet aggregation, resulting in ischemic or electrical sudden cardiac death. Management of benign ventricular arrhythmias should consist largely of abstinence from sympathetic nervous system stimulants; when pharmacotherapy is required, beta-adrenergic blockers are the agents of choice. Optimal therapy for potentially lethal ventricular arrhythmias is not yet firmly established for amiodarone and implantable cardioverter-defibrillator (ICD) use; however, appropriate secondary prevention utilizes aspirin, beta blockers, angiotensin-converting enzyme inhibitors, and revascularization procedures. Currently, ICDs are established as a first-choice intervention for malignant ventricular arrhythmias, while the adjunctive and independent use of beta-blocker therapy and amiodarone is undergoing further investigation.

Holter triage ambulatory ECG analysis. Accuracy and time efficiency.

Triage ambulatory electrocardiographic (ECG) analysis permits relatively unskilled office workers to submit 24-hour ambulatory ECG Holter tapes to an automatic instrument (model 563, Del Mar Avionics, Irvine, CA) for interpretation. The instrument system "triages" what it is capable of automatically interpreting and rejects those tapes (with high ventricular arrhythmia density) requiring thorough analysis. Nevertheless, a trained cardiovascular technician ultimately edits what is accepted for analysis. This study examined the clinical validity of one manufacturer's triage instrumentation with regard to accuracy and time efficiency for interpreting ventricular arrhythmia. A database of 50 Holter tapes stratified for frequency of ventricular ectopic beats (VEBs) was examined by triage, conventional, and full-disclosure hand-count Holter analysis. Half of the tapes were found to be automatically analyzable by the triage method. Comparison of the VEB accuracy of triage versus conventional analysis using the full-disclosure hand count as the standard showed that triage analysis overall appeared as accurate as conventional Holter analysis but had limitations in detecting ventricular tachycardia (VT) runs. Overall sensitivity, positive predictive accuracy, and false positive rate for the triage ambulatory ECG analysis were 96, 99, and 0.9%, respectively, for isolated VEBs, 92, 93, and 7%, respectively, for ventricular couplets, and 48, 93, and 7%, respectively, for VT. Error in VT detection by triage analysis occurred on a single tape. Of the remaining 11 tapes containing VT runs, accuracy was significantly increased, with a sensitivity of 86%, positive predictive accuracy of 90%, and false positive rate of 10%. Stopwatch-recorded time efficiency was carefully logged during both triage and conventional ambulatory ECG analysis and divided into five time phases: secretarial, machine, analysis, editing, and total time. Triage analysis was significantly (P < .05) more time efficient for the machine, analysis, and total time phases and required significantly more time in the editing phases. The triage analysis was limited by the inability of the automatic methodology to detect a specific VT waveform contained on one tape. This result which caused substantial loss of sensitivity for VT, emphasizes the necessity for careful quality control and editing of all automatic Holter analysis methods.

Association between ease of suppression of ventricular arrhythmia and survival.

BACKGROUND: We tested the hypothesis that patients whose ventricular arrhythmias are easy to suppress have a lower rate of arrhythmic death, defined as arrhythmic death and nonfatal cardiac arrest, the primary end point in the Cardiac Arrhythmia Suppression Trials (CAST-I and CAST-II), than patients whose ventricular arrhythmias are hard to suppress. In addition, we evaluated the association between ease of suppression of ventricular arrhythmias and mortality of all causes. METHODS AND RESULTS: CAST-I investigated the effect on arrhythmic death of ventricular premature depolarization (VPD) suppression achieved by three drugs, encainide, flecainide, and moricizine, at two different dose levels; CAST-II investigated the same effect, using moricizine alone at three dose levels. If suppression was achieved, patients were randomized to the effective active drug or corresponding placebo. To examine the independence of easily suppressed ventricular arrhythmias as a predictor of arrhythmic death, we adjusted statistically for other variables that were related both to ease of suppression and arrhythmic death. Patients with ventricular arrhythmias (n = 1778) that were easy to suppress had fewer arrhythmic deaths during follow-up than those with ventricular arrhythmias that were hard to suppress (n = 1173) (relative risk, .59; P = .003). Patients whose VPDs were easily suppressed were older and had a lower frequency of prior history of heart failure and myocardial infarction. They also had a higher incidence of anterior myocardial infarction, VPD frequency, and average ejection fraction. After adjusting for these variables, we found that easily suppressed ventricular arrhythmias were still significant predictors of arrhythmic death (relative risk, .66; P = .013). CONCLUSIONS: This study shows that the ease of VPD suppression identifies a subgroup of postmyocardial infarction patients who have low risk of arrhythmic death.

Beta-blocker therapy in the Cardiac Arrhythmia Suppression Trial. CAST Investigators.

The Cardiac Arrhythmia Suppression Trial (CAST) showed antiarrhythmic drug suppression of asymptomatic or mildly symptomatic ventricular arrhythmias in survivors of myocardial infarction to be harmful. This study retrospectively searched the CAST results for evidence of mortality and morbidity reduction in patients receiving optional beta-blocker therapy. All enrolled (n = 2,611) and suppressed main study (n = 1,735) CAST patients with an ejection fraction of < or = 40% were examined using univariate analysis, Kaplan-Meier curves, and a Cox proportional-hazards multivariate analysis with respect to optional beta-blocker therapy prescribed at baseline. CAST patients receiving beta-blocker therapy had significantly enhanced survival at 30 days, and at 1 and 2 years of follow-up against all-cause and arrhythmic death or nonfatal cardiac arrest. Multivariate analysis showed beta-blocker therapy to be independently associated with a one-third reduction in arrhythmic death or cardiac arrest (p = 0.036). In CAST patients with a history of congestive heart failure, beta-blocker therapy was independently associated with longer time to occurrence of new or worsened congestive heart failure (p = 0.015). This study supports the secondary preventive benefit of beta-blocker therapy in high-risk post-myocardial infarction patients, and calls attention to the possible preventive benefit of beta-blocker therapy against proarrhythmic events experienced in the CAST.

Morphological and quantitative angiographic analyses of progression of coronary stenoses. A comparison of Q-wave and non-Q-wave myocardial infarction.

BACKGROUND: The purpose of this study was to determine differences in coronary stenosis severity and morphology and time course of progression between Q-wave and non-Q-wave myocardial infarction (MI). METHODS AND RESULTS: We studied 32 patients with new Q-wave MI and 38 patients with new non-Q-wave MI who underwent coronary angiography both before and after MI without interval revascularization procedures. Quantitative coronary angiographic analysis was performed by the caliper method, and morphological analysis of coronary angiograms was obtained before and soon after acute MI. Before infarction, the stenosis severity at the site of future MI was worse in Q-wave (44 +/- 25%) versus non-Q-wave (23 +/- 35%) MI patients (P < .01). Eccentric and irregular plaques were more common in Q-wave MI patients (18 of 32, 56%, versus 5 of 38, 13%; P < .001). Non-Q-wave MI patients were more frequently found to have significant collaterals after MI compared with Q-wave MI patients (18 of 38, 47%, versus 1 of 32, 3%; P < .001) despite no difference in post-MI stenosis severity. Analysis according to time interval after pre-MI angiography showed that 9 of 11 patients (82%) with Q-wave MI < 18 months later had a stenosis of > or = 50% versus 7 of 21 (33%) with an interval > 18 months (P < .05). By comparison, non-Q-wave MI patients tended to fall into two categories regardless of time of progression: Either minimal or no stenosis (< 20%) or else a severe stenosis (> 70%) was typically present. CONCLUSIONS: The atheromatous plaque substrate is different in Q-wave and non-Q-wave MI. Non-Q-wave MI occurs typically at a site shown by pre-MI angiography to involve either minimal luminal narrowing or a severe stenosis before MI, which is usually nonulcerated. By comparison, Q-wave MI follows a moderate stenosis in which the plaque is eccentric and ulcerated. Such differences culminate in differences in thrombus lability and collateral development and consequently in different clinical profiles.

Power law analysis of the signal-averaged electrocardiogram for identification of patients with ventricular tachycardia: effect of bundle branch block.

Signal-averaged ECGs that use time-domain analysis are useful for the identification of patients at risk for ventricular tachycardia (VT). Bundle branch block (BBB) and other conduction defects reduce the value of this approach, but frequency-domain analysis has shown promise in such patients. The purpose of the present study was to examine a new frequency-domain approach to signal-averaged ECGs in patients with and without BBB: power law scaling (PLS). PLS was performed by plotting the power spectrum of the entire signal-averaged ECG on a plot of log power versus log frequency and determining the slope (beta) by least-squares regression. This method was studied in 346 patients. Results of discriminant analysis revealed better sensitivity, specificity, positive predictive value, negative predictive value, and percentage correctly predicted when this method was compared with time-domain indexes. A large proportion of the variance in PLS (19%) was found to be due to findings in patients with VT; whereas the best time-domain index, duration of the filtered QRS signal, explained only 6% of the variance in the group with VT. Mean levels of PLS (+/- standard deviation) were decreased for the group with VT (-3.55 +/- 0.95) as compared with the group without VT (-4.34 +/- 0.59; p < 0.001), suggesting a decrease in the time correlation of the signal. Thus this method of frequency-domain analysis of the signal-averaged ECG was useful in identifying patients with sustained VT despite the presence of significant conduction defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory (Holter) electrocardiography signal-averaging: a current perspective.

Signal-averaging is an emerging new application of the ambulatory ECG. Whereas real-time signal-averaging of the high-resolution ECG has led to the measurement of abnormal QRS complex parameters and to the detection of ventricular late potentials in patients with a history of ventricular tachycardia or fibrillation at increased risk of an arrhythmic event, similar measurements can also be derived from ambulatory ECG tape recordings. This review describes the technical differences between real-time and ambulatory high-resolution ECG signal-averaging, and the early clinical studies that correlated measured QRS complex parameters and defined the agreement of late potential detection with the two technologies. Although there appears to be a promising cost-effective benefit from ambulatory ECG signal-averaging, limitations imposed by the technical differences must be recognized, and additional investigation is needed to define the appropriate clinical use and criteria for best diagnostic and prognostic value.