David E. Ward

Risk stratification for arrhythmic events in postinfarction patients based on heart rate variability, ambulatory electrocardiographic variables and the signal-averaged electrocardiogram

The value of heart rate variability, ambulatory electrocardiographic (ECG) variables and the signal-averaged ECG in the prediction of arrhythmic events (sudden death or life-threatening ventricular arrhythmias) was assessed before hospital discharge in 416 consecutive survivors of acute myocardial infarction. During the follow-up period (range 1 to 1,112 days), there were 24 arrhythmic events and 47 deaths. The initial relation between several prognostic factors and arrhythmic events was explored with use of the Kaplan-Meier product limit estimates of survival function. Impaired heart rate variability less than 20 ms (p less than 0.0000), late potentials (p less than 0.0000), ventricular ectopic beat frequency (p less than 0.0000), repetitive ventricular forms (p less than 0.0000), left ventricular ejection fraction less than 40% (p less than 0.02) and Killip class (p less than 0.02) were identified as significant univariate predictors of arrhythmic events. When these variables were analyzed by using a stepwise Cox regression model, only impaired heart rate variability, followed by late potentials and repetitive ventricular forms remained independent predictors of arrhythmic events. The combination of impaired heart rate variability and late potentials had a sensitivity of 58%, a positive predictive accuracy of 33% and a relative risk of 18.5 for arrhythmic events and was superior to other combinations including those incorporating left ventricular function, exercise ECG, ventricular ectopic beat frequency and repetitive ventricular forms. These results suggest that a simple method of assessment based on heart rate variability and the signal-averaged ECG can select a small subgroup of survivors of myocardial infarction at high risk of future life-threatening arrhythmias and sudden death.

QT Dispersion: Problems of Methodology and Clinical Significance

QT Dispersion. QT dispersion is defined as the difference in QT interval between the different leads of the surface 12‐lead ECG. This may provide an indirect measure of the underlying inhomogeneity of myocardial repolarization, which is believed to be important in arrhylhmogenesis. Methodology for determining QT dispersion varies significantly between studies, and the results of these studies need to be interpreted in light of the methodology used. Although QT dispersion is developing into an important research tool, as yet it has no established role in clinical practice. Once standardization of methodology is achieved a clinical role may emerge, particularly in the assessment of patients before and after intervention aimed at reduction of arrhythmia risk.

Prognostic value of baroreflex sensitivity testing after acute myocardial infarction.

BACKGROUND--Disturbances of autonomic function are recognised in both the acute and convalescent phases of myocardial infarction. Recent studies have suggested that disordered autonomic function, particularly the loss of protective vagal reflexes, is associated with an increased incidence of arrhythmic deaths. The purpose of this study was to compare the value of differing prognostic indicators with measures of autonomic function and to assess the safety of arterial baroreflex testing early after infarction. METHODS--As part of a prospective trial of risk stratification in post-infarction patients arterial baroreflex sensitivity, heart rate variability, long term electrocardiographic recordings, exercise stress testing, and ejection fraction were recorded between days 7 and 10 in 122 patients with acute myocardial infarction. RESULTS--During a one year follow up period there were 10 arrhythmic events. Baroreflex sensitivity was appreciably reduced in these patients suffering arrhythmic events (1.73 SD (1.49) v 7.83 (4.5) ms/mm hg, 95% confidence interval (CI) 4.8 to 7.3, p = 0.0001). Significant correlations were noted with age (r = -0.68, p less than 0.001) but not left ventricular function. When baroreflex sensitivity was adjusted for the effects of age and ventricular function baroreflex sensitivity was still considerably reduced in the arrhythmic group (2.1 v 7.57 ms/mm Hg, p less than 0.0001). Depressed baroreflex sensitivity carried the highest relative risk for arrhythmic events (23.1, 95% CI 7.7 to 69.2) and was superior to other prognostic variables including left ventricular function (10.4, 95% CI 3.3 to 32.6) and heart rate variability (10.1, 95% CI 5.6 to 18.1). No major complications were noted with baroreflex testing and in particular no patients developed ischaemic or arrhythmic symptoms during the procedure. CONCLUSIONS--Disordered autonomic function as measured by depressed baroreflex sensitivity or reduced heart rate variability was associated with an increase incidence of arrhythmic events in post-infarction patients. Baroreflex testing can be safely performed in the immediate post-infarction period.

Efficacy and tolerability of transvenous low energy cardioversion of paroxysmal atrial fibrillation in humans

OBJECTIVES This study investigated the efficacy and tolerability of low energy shocks for termination of atrial fibrillation in patients, using an endocardial electrode configuration that embraced both atria. BACKGROUND In animals, low energy biphasic shocks delivered between electrodes in the coronary sinus and right atrium have effectively terminated atrial fibrillation. If human defibrillation thresholds are sufficiently low, atrial defibrillation could be achieved in conscious patients using an implanted device. METHODS Twenty-two consecutive patients with stable atrial fibrillation were studied during electrophysiologic testing. Biphasic R wave synchronous shocks were delivered between large surface area electrodes in the coronary sinus and high right atrium, using a step-up voltage protocol starting at 10 or 20 V and increasing to a maximum of 400 V. Patients were conscious at the start of the study and were asked to report on symptoms but were sedated later if shocks were not tolerated. RESULTS Cardioversion was achieved in all 19 patients who completed the study, with a mean (+/- SD) leading-edge voltage of 237 +/- 55 V (range 140 to 340) and mean energy of 2.16 +/- 1.02 J (range 0.7 to 4.4). The mean maximal shock delivered without sedation was 116 +/- 51 V (range 60 to 180). No proarrhythmia or mechanical complications occurred. CONCLUSIONS The delivery of biphasic R wave synchronous shocks between the high right atrium and coronary sinus can terminate atrial fibrillation with very low energies. General anaesthesia is not required, and a minority of fully conscious patients are able to tolerate this method of cardioversion.

Baroreflex sensitivity and electrophysiological correlates in patients after acute myocardial infarction.

BACKGROUND Several studies have identified transient disturbances of autonomic function during the acute and recovery phases of myocardial infarction, and it has recently been suggested that survivors of acute myocardial infarction with depressed vagal tone may be at increased risk of sudden or arrhythmic death. METHODS AND RESULTS To investigate this hypothesis, parasympathetic function was assessed by arterial baroreflex sensitivity (BRS) testing (using the phenylephrine method) and by heart rate variability (HRV) analysis from 24-hour Holter recording in 68 patients at day 7-10 after infarction. The relation between autonomic tone and markers of arrhythmic propensity, including programmed ventricular stimulation (PVS) and late potentials in addition to other clinical variables, was examined. BRS for the whole group was 7.0 +/- 4.7 msec/mm Hg and was inversely correlated with age (r = 0.53, p less than 0.001) but not with left ventricular ejection fraction (r = 0.035, p = NS). In those patients in whom sustained monomorphic ventricular tachycardia (SMVT) was induced, BRS was significantly reduced (p = 0.001) as was HRV (p = 0.007) and left ventricular ejection fraction (p = 0.022). The strongest association between any variable (including HRV, BRS, late potentials, left ventricular ejection fraction, exercise testing, Q waves, and infarct site) and the induction of sustained monomorphic ventricular tachycardia was depressed BRS with a relative risk of 36.28 (95% confidence interval, 5-266). CONCLUSIONS This study confirms that depressed BRS identifies a subgroup at high risk for arrhythmic events after myocardial infarction and that programmed ventricular stimulation may be safely limited to this group without any loss of predictive accuracy.

Assessment of QT dispersion in symptomatic patients with congenital long QT syndromes

It has been suggested that QT dispersion recorded on the surface electrocardiogram may be a predictor of arrhythmic events in patients with congenital QT prolongation. To evaluate this, 9 patients (6 female, mean age 17.6 years) with congenital long QT syndromes, all of whom had syncope and documented torsades de pointes, were studied. Patients were studied off treatment and during therapy with beta-blocking agents. Three patients were also studied after left stellate ganglionectomy. An age-matched control group was also studied. Good quality 12-lead electrocardiograms were recorded from all patients. For each lead, QT and RR intervals were measured, and QTc value was calculated. QT and QTc dispersions were calculated for each patient. Patients had a significantly longer mean QT interval compared with that of the control group (450 +/- 100 vs 359 +/- 63 ms; p = 0.015) at similar mean RR intervals (736 +/- 231 vs 783 +/- 289 ms), with a longer mean QTc value (0.53 +/- 0.08 vs 0.41 +/- 0.02 s1/2; p = 0.004). Patients also had longer QT and QTc dispersions compared with those of the control group (110 +/- 45 vs 43 +/- 12 ms [p = 0.004], and 0.108 +/- 0.03 vs 0.05 +/- 0.02 s1/2 [p = 0.002], respectively). QT and QTc dispersions on and off beta-blocking agents were not significantly different. Comparing patients with frequent and those with infrequent symptoms, there was no difference in QT or QTc dispersion either off treatment or during therapy with beta-blocking agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of intravenous propranolol on QT interval. A new method of assessment.

Changes in the QT and QTc intervals were studied in 16 patients by atrial pacing at rates of 100, 130, and 150 beats/minute. In all patients the measured QT shortened when the atrial paced rate was increased, but when corrected for heart rate the QTc lengthened. Intravenously administered propranolol produced a bradycardia and a lengthening of the QT interval in 15 of the 16 patients studied. When the QT interval was corrected for heart rate using Bazetts formula the QTc was shortened in 13 patients, unchanged in one, and lengthened in two. However, when the QT interval was measured at identical atrial paced rates the QT of the 15 patients studied was lengthened in 10 and unchanged in five. In none was the QT interval shortened. These results show firstly that Bazetts formula is unsuitable for correction of QT interval changes induced by atrial pacing, and secondly that, though intravenously administered propranolol usally produces a shortening of the QTc, when its effect is assessed directly by using an identical atrial paced rate the QT interval usually lengthens, or may remain unchanged, but never shortens. It is suggested that the formal assessment of drug induced QT interval changes should be made at identical atrial paced rates.

ADENOSINE IN THE DIAGNOSIS OF BROAD COMPLEX TACHYCARDIA

Adenosine, in incremental bolus doses up to 0.25 mg/kg, was given during regular broad complex tachycardia in 26 patients examined in an electrophysiological laboratory. In 8 of 9 cases of broad complex supraventricular tachycardia (SVT) the arrhythmia was terminated, converted into a narrow complex SVT, or atrioventricular block was induced. In all 9 cases of narrow complex SVT, the arrhythmia was stopped, or atrioventricular block was induced. The arrhythmia was stopped in only 1 of 17 cases of ventricular tachycardia. 6 patients with atrial fibrillation and ventricular pre-excitation were given adenosine, with no effect on mean ventricular rate (averaged over 3 s), although a significant, but short-lived, reduction in minimum RR interval was observed (from 242 ms, SD 45, to 217 ms, SD 39). The mean dose of adenosine required to stop the arrhythmia or to induce atrioventricular block in broad complex SVT (0.14 mg/kg, SD 0.04) was higher than in narrow complex SVT (0.11 mg/kg, SD 0.04). No adverse haemodynamic effects were observed in any patient, and large doses were tolerated by the patients with ventricular tachycardia. The data show that adenosine has a useful role in the diagnosis and treatment of regular broad complex tachycardia.

Optimal atrioventricular delay at rest and during exercise in patients with dual chamber pacemakers: a non-invasive assessment by continuous wave Doppler.

The optimal atrioventricular delay at rest and during exercise was investigated in nine patients with heart block and implanted dual chamber pacemakers. All patients studied had normal left ventricular function and a normal sinus node rate response to exercise. Cardiac output was measured by continuous wave Doppler and was calculated as the product of stroke distance measured by Doppler at the left ventricular outflow, aortic root area measured by M mode echocardiography, and heart rate. Pacemakers were programmed in the DDD mode. Cardiac output was measured with the patient at rest while supine and while erect and at the peak of submaximal exercise (the end of stage 1 of the Bruce protocol) with the pacemakers programmed to the following atrioventricular intervals: 75-80 ms, 100-110 ms, 140-150 ms, and 200 ms. During exercise the basic pacing rate was programmed to 70 beats/min. Cardiac output at rest while supine and erect was greatest with an atrioventricular delay of 140-150 ms and it was significantly higher than that with an atrioventricular delay of 75-80 ms. On average there was a 31% decrease in cardiac output when patients stood up. During treadmill exercise, however, cardiac output was greatest when the atrioventricular delay was 75-80 ms, and this was significantly higher than the cardiac output with atrioventricular delays of 150 and 200 ms. During exercise 1:1 atrioventricular relations were maintained in patients at all atrioventricular intervals. In patients with atrioventricular sequential pacemakers cardiac output at rest is greatest with an atrioventricular delay of 140-150 ms but during exercise the optimal atrioventricular delay is shorter. Rate modulation of the atrioventricular interval may improve the haemodynamic response and possibly exercise tolerance in patients with dual chamber pacemakers.

RELATIVE EFFICACY OF VARIOUS PHYSICAL MANOEUVRES IN THE TERMINATION OF JUNCTIONAL TACHYCARDIA

The ability of four vagotonic physical manoeuvres to terminate paroxysmal junctional tachycardias was tested in 35 patients with inducible and sustained arrhythmia. Each manoeuvre was used up to three times in an attempt to terminate an induced tachycardia and was judged to be effective if it terminated two out of the three induced episodes. The Valsalva manoeuvre in the supine position was effective in 19 (54%), right carotid sinus massage in 6 (17%), left carotid sinus massage in 2 (5%), and the diving reflex in 6 (17%) cases. 4 of the 6 patients who responded to right carotid sinus massage and all patients who responded to the diving reflex also responded to the Valsalva manoeuvre. The Valsalva manoeuvre while standing was effective in 9 (20%) patients only. Patients in whom the manoeuvres terminated the tachycardias were significantly younger than those who did not respond (median age: 30 vs 45 years, p less than 0.01). Physical manoeuvres were much more successful in terminating atrioventricular re-entry tachycardias (19/24) than atrioventricular nodal re-entry tachycardias (3/11, p less than 0.01). Efficacy of the manoeuvres was related to their bradycardic effect in sinus rhythm.