J. Edwin Atwood

Effect of beta-adrenergic blockade on exercise performance in patients with chronic atrial fibrillation.

Beta-adrenergic blocking agents are commonly used in combination with digitalis to control excessive heart rate during exercise in patients with chronic atrial fibrillation. However, little is known about the effect of beta-adrenergic blockade on exercise capacity in these patients. Accordingly, a randomized, double-blind, cross-over placebo-controlled study was performed to assess the efficacy of celiprolol, a new cardioselective beta-blocker with partial intrinsic sympathomimetic activity, on exercise performance in nine men with chronic atrial fibrillation. All but one patient was receiving maintenance digitalis during the study. Heart rate, blood pressure and gas exchange variables were measured at rest and during treadmill exercise testing while the patients were receiving maintenance celiprolol or placebo. Significant reductions in heart rate and systolic blood pressure compared with control values were observed at submaximal exercise, at the gas exchange anaerobic threshold and at maximal exertion while the patients were taking celiprolol. However, oxygen uptake at the gas exchange anaerobic threshold during celiprolol therapy was 12.3 versus 14.0 ml oxygen/kg per min during placebo administration (a 12% difference, p less than 0.01). Similarly, oxygen uptake at maximal exertion during celiprolol therapy was 17.6 versus 21.0 ml/kg per min during placebo administration (a 16% difference, p less than 0.01). Treadmill time was also reduced during the celiprolol phase compared with placebo (11.3 versus 10.3 minutes; a 19% difference, p less than 0.01). These results indicate that in patients with atrial fibrillation the major beneficial effects of beta-adrenergic blockade--reduced submaximal and maximal exercise heart rate and blood pressure--must be weighed against the decrease in exercise capacity.

Increased exercise capacity after digoxin administration in patients with heart failure

Failure to objectively assess the effect of digitalis on exercise capacity has resulted in controversy regarding its use in patients with chronic congestive heart failure. To clarify this situation, maximal treadmill testing with respiratory gas exchange analysis was performed on 11 patients (mean age 57 +/- 9 years) with chronic congestive heart failure with and without digoxin therapy. Ten of the 11 had a consistent third sound gallop, and the mean ejection fraction of the group was 24 +/- 10%. Rest heart rate was significantly higher (91 +/- 16 versus 102 +/- 16 beats/min; p less than 0.05) and rest systolic blood pressure was significantly reduced in the absence of digoxin (130 +/- 23 versus 121 +/- 15 mm Hg; p less than 0.05). No differences in heart rate or blood pressure were observed during exercise. Significant increases in ventilatory oxygen uptake were observed with digoxin submaximally (3.0 mph, 0% grade), at the gas exchange anaerobic threshold and at maximal exercise (mean increase of 2.6 ml/kg per min; p less than 0.02). An improvement in the estimated ratio of ventilatory dead space to tidal volume (VD/VT), an index of physiologic efficiency, occurred throughout exercise during digoxin therapy, and there was a significant negative correlation between the change in maximal oxygen uptake and change in maximal estimated VD/VT (r = -0.63; p less than 0.05). Thus, digoxin therapy is associated with a significant improvement in exercise capacity in patients with chronic heart failure, most likely due to an improved matching of ventilation to perfusion.

Optimal sampling interval to estimate heart rate at rest and during exercise in atrial fibrillation

To investigate the ideal sampling interval for the estimation of heart rate (HR) at rest and during exercise in atrial fibrillation (AF), maximal exercise testing with continuous electrocardiographic acquisition was performed in 10 patients with chronic AF (mean age 66 +/- 4 years) and 10 subjects in normal sinus rhythm (mean age 31 +/- 6 years). Measurements of HR were obtained at 9 different sampling intervals (1, 2, 3, 6, 10, 15, 20, 30 and 60 seconds) at rest and 7 different sampling intervals (1, 2, 3, 6, 10, 15 and 20 seconds) during the last 30 seconds of each minute during exercise. The HR obtained from each interval was compared with true HR (determined by a 4-minute sample at rest and by the last 30 seconds of each minute during exercise). Among patients with AF, large differences were observed between the HR obtained and true HR, both at rest and during exercise, using small sampling intervals. The mean of these differences ranged between 16 +/- 11 beats/min (range 14 to 22) using 1-second sampling intervals and 2.2 +/- 2.0 beats/min (range 1.6 to 4.4) using 20-second sampling intervals during progressive exercise. Variability of the HR obtained from a given random sample was also high when short sampling intervals were used among patients with AF. These observations were contrasted by subjects in normal sinus rhythm, among whom neither variability nor measurement error were influenced remarkably by changing the sampling interval or increasing HR.

Acquired Left Ventricular-Right Atrial Communication Gerbode-Type Defect

Left ventricular‐right atrial (LV‐RA) communications are rare intracardiac defects, often congenital in nature and clinically apparent during childhood. Acquired LV‐RA shunts are encountered occasionally in the adult population as a result of a defect in the upper portion of the membranous ventricular septum. We describe the clinical and echocardiographic features of an elderly patient with an acquired LV‐RA communication in the setting of an aortic composite valve graft and endocarditis. We also review the anatomical features and hemodynamic consequences of such defects.

Review of studies using multivariable analysis of clinical and exercise test data to predict angiographic coronary artery disease.

Multivariable analysis of clinical and exercise test variables has the potential to become both a useful tool for assisting in the diagnosis of coronary artery disease and reducing the cost of evaluating patients with suspected coronary disease. Managed care and capitation require that tests such as the exercise test or its replacements, be used only when they can accurately and reliably identify which patients need medications, counseling, or further evaluation or intervention. The replacements for the standard exercise electrocardiogram test require expensive equipment and personnel, and their incremental value is currently being evaluated. Because general practitioners are to function as gatekeepers and decide which patients must be referred to the cardiologist, they will need to use the basic tools they have available (ie, history, physical exam, and the exercise test) in an optimal fashion. However, the discriminating power of the variables from the medical history and exercise test remains unclear because of inadequate study design and differences in study populations. There is a need for further evaluation of these routinely obtained variables to improve the accuracy of prediction algorithms especially in women. Of paramount concern is the need to avoid workup bias by having patients agree to testing before the decision for angiography is made. The portability and reliability of these equations must be shown because access to specialized care must be safeguarded. By reviewing the available studies considering clinical and exercise test variables to predict coronary angiographic findings, we have attempted to provide guidelines and recommendations for a more uniform approach to this endeavor in future investigations. Hopefully, the next generation of multivariable equations will be robust and portable, and empower the clinician to assure the cardiac patient access to appropriate cardiac care.

Improvement in ventricular function during exercise studied with radionuclide ventriculography after cardiac rehabilitation

A heterogeneous group of 19 consecutive patients with coronary artery disease were studied with radionuclide ventriculography before and after a mean of 6 months of exercise training. Ejection fraction was measured at rest, at matched submaximal supine work loads and during maximal supine bicycle exercise. After training there was no change in mean ejection fraction at rest or during maximal exercise, but a higher maximal mean systolic blood pressure, heart rate and work load were achieved. At equivalent submaximal work loads after training, similar levels of mean heart rate and systolic blood pressure were reached but a statistically greater mean ejection fraction was obtained. These preliminary results suggest that exercise training may improve cardiac function during exercise in selected patients with coronary disease. A randomized study using similar techniques has been initiated.

Hemodynamic determinants of exercise capacity in chronic atrial fibrillation

To evaluate the response of patients with chronic atrial fibrillation (AF) to exercise, 79 male patients (mean age 64 +/- 1 years) with AF underwent resting two-dimensional and M-mode echocardiography and symptom-limited treadmill testing with ventilatory gas exchange analysis. Patients were classified by underlying disease into five subgroups: no underlying disease (LONE: n = 17), hypertension (HT: n = 11), ischemic heart disease (n = 13), cardiomyopathy or history of congestive heart failure (CHF: n = 26), and valvular disease (n = 12). A higher maximal heart rate than expected for age was observed (175 vs 157 beats/min), which was most notable in the LONE and HT subgroups. Maximal oxygen uptake (VO2 max) was lower than expected for age in all groups. Patients with CHF had a lower resting ejection fraction than all other patients (p < 0.001), a lower VO2 max, and a lower maximal heart rate than LONE and HT patients (p < 0.001). Stepwise regression analysis demonstrated that echocardiographic measurements at rest were poor predictors of VO2 max and VO2 at the ventilatory threshold. Among clinical, morphologic, and exercise variables, maximal systolic blood pressure accounted for the greatest variance in exercise capacity, but it explained only 35%. In patients with AF the higher than predicted maximal heart rates may be a compensatory mechanism for maintaining exercise capacity after the loss of normal atrial function. However, even in the absence of underlying disease, it does not appear to compensate fully for a compromised exercise capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

The signal averaged surface electrocardiogram and the identification of late potentials

V ENTRICULAR TACHYARRHYTHMIAS are a major cause of sudden cardiac death, especially in patients after myocardial infarction.‘** Accurate detection of those prone to malignant ventricular arrhythmias is essential to the prevention of sudden death. Many parameters, including clinical findings, and results from exercise testing, holter monitoring, and cardiac catheterization have been used to identify patients at high risk of sudden death.3-8 More recently, electrophysiologic stimulation testing in the cardiac catheterization laboratory has been used as a method of evaluating these patients.g*‘O The cost and invasive nature of this procedure, however, makes it impractical for use as a screening test for large numbers of patients. Tests designed to evaluate large populations at risk should be noninvasive, relatively inexpensive, and easily performed. The signal averaged electrocardiogram (ECG) may be such a screening test. This noninvasive, inexpensive procedure incorporates high gain amplification and signal averaging techniques to detect from ECG recordings on the body surface low amplitude, high frequency signals in or near the terminal portion of the QRS complex (Fig 1). There are many synonyms for these signals including delayed depolarization, arrhythmogenic ventricular activity (AVA), delayed wave-form activity (D wave), and ventricular late potentials (VLPs). These signals, called late potentials or LPs in this review (Fig 2) are rarely identified on routine ECG. Late potentials are thought to represent slow or delayed conduction through the myocardium. Within the last 10 years, numerous studies have provided convincing evidence that delayed conduction plays an important role in the genesis of ventricular arrhythmias.“-” Additional studies have corroborated the capacity of the highly amplified signal averaged ECG to detect such delayed activity.“-*’ Many investigators have used direct epicardial and endocardial mapping techniques to record delayed, fragmented electrical activity in patients and animals with ventricular arrhythmias.‘1-20,26-30 Several investigators have used both the body surface signal averaged ECG and endocardial catheter techniques to record delayed potentials in man and animals with ventricular tachyarrhythmias. They have found a close temporal correlation between the delayed potentials recorded by the two methods.‘g*20~30 While many studies lend theoretical support to the use of signal averaging techniques in identifying patients at risk of developing dangerous ventricular arrhythmias, the clinical role of this technique has not been defined. The intention of this review is to summarize the methodology and principles of signal averaged electrocardiography and to analyze critically many of the published reports to better define its current status.

Comparison of sotalol versus amiodarone in maintaining stability of sinus rhythm in patients with atrial fibrillation (Sotalol-Amiodarone Fibrillation Efficacy Trial [Safe-T])

The Sotalol-Amiodarone Fibrillation Efficacy Trial (SAFE-T) is a randomized, double-blind, multicenter, placebo-controlled trial in which the effects of sotalol and amiodarone in maintaining stability of sinus rhythm are being examined in patients with persistent atrial fibrillation at 20 Veterans Affairs medical centers. The time to the occurrence of atrial fibrillation or flutter in patients with atrial fibrillation converted to sinus rhythm is the primary outcome measure, with a number of parameters as secondary end points. SAFE-T had randomized 665 patients when enrollment terminated on October 31, 2001. Follow-up of patients continued until October 31, 2002, for a maximum period of 54 months and a minimum period of 12 months for all patients.

Carotid Bruits and Cerebrovascular Disease Risk A Meta-Analysis

Background and Purpose— Current guidelines recommend against routine auscultation of carotid arteries, believing that carotid bruits are poor predictors of either underlying carotid stenosis or stroke risk in asymptomatic patients. We investigated whether the presence of a carotid bruit is associated with increased risk for transient ischemic attack, stroke, or death by stroke (stroke death). Methods— We searched Medline (1966 to December 2009) and EMBASE (1974 to December 2009) with the terms “carotid” and “bruit.” Bibliographies of all retrieved articles were also searched. Articles were included if they prospectively reported the incidence of transient ischemic attack, stroke, or stroke death in asymptomatic adults. Two authors independently reviewed and extracted data. Results— We included 28 prospective cohort articles that followed a total of 17 913 patients for 67 708 patient-years. Among studies that directly compared patients with and without bruits, the rate ratio for transient ischemic attack was 4.00 (95% CI, 1.8 to 9.0, P<0.0005, n=5 studies), stroke was 2.5 (95% CI, 1.8 to 3.5, P<0.0005, n=6 studies), and stroke death was 2.7 (95% CI, 1.33 to 5.53, P=0.002, n=3 studies). Among the larger pool of studies that provided data on rates, transient ischemic attack rates were 2.6 per 100 patient-years (95% CI, 2.0 to 3.2, P<0.0005, n=24 studies) for those with bruits compared with 0.9 per 100 patient-years (95% CI, 0.2 to 1.6, P=0.02, n=5 studies) for those without carotid bruits. Stroke rates were 1.6 per 100 patient-years (95% CI, 1.3 to 1.9, P<0.0005, n=26 studies) for those with bruits compared with 1.3 per 100 patient-years (95% CI, 0.8 to 1.7, P<0.0005, n=6) without carotid bruits, and death rates were 0.32 (95% CI, 0.20 to 0.44, P<0.005, n=13 studies) for those with bruits compared with 0.35 (95% CI, 0.00 to 0.81, P=0.17, n=3 studies) for those without carotid bruits. Conclusion— The presence of a carotid bruit may increase the risk of cerebrovascular disease.