Underuse of beta-blockers following myocardial infarction: a tale of two cities.

AIMS: To measure factors associated with underuse of beta-blocker therapy after myocardial infarction (MI). METHODS: The Newcastle and Perth collaborating centres of the World Health Organization (WHO) MONICA project (to MONItor trends and determinants of Cardiovascular disease) systematically evaluated all patients admitted to hospital in their respective regions with possible MI. A total of 1766 patients in Newcastle and 4,503 patients in Perth, discharged from hospital after confirmed MI from 1985 to 1993, were studied. Rates of beta-blocker use before and after hospital discharge were evaluated and correlates of beta-blocker use determined. RESULTS: Beta-blocker use was similar in Newcastle and Perth before MI (21% of patients in each centre). During hospital admission, beta-blocker therapy was initiated nearly twice as frequently in Perth compared with Newcastle (66 vs 36%, respectively) and more patients were discharged from hospital on beta-blockers in Perth (68%) than in Newcastle (45%). The main factors associated with underuse of beta-blockers in multivariate analysis were geographical centre (odds ratio (OR) for Newcastle compared with Perth 0.3; 95% confidence interval (CI) 0.3-0.3), a history of previous MI (OR 0.6, 95% CI 0.5-0.7), admission to hospital in earlier years (OR 0.4, 95% CI 0.3-0.4 for years 1985-87 compared with years 1991-93), diabetes (OR 0.6, 95% CI 0.5-0.8) and the concomitant use of diuretics (OR 0.5, 95% CI 0.4-0.6) and calcium antagonists (OR 0.6, 95% CI 0.5-0.8). CONCLUSIONS: Underuse of beta-blockers after MI was strongly related to hospital prescribing patterns and not to community use of beta-blockers. Underuse occurred in patients with diabetes and in patients with left ventricular dysfunction, patients who stand to benefit most from beta-blocker use following MI.

Dietary n-3 fatty acids alter the contractile response to thromboxane A(2) agonists of porcine coronary arteries.

Dietary supplementation with marine fish oils rich in n-3 fatty acids reduces circulating thromboxane A(2) (TxA(2)). However, the effects on thomboxane A(2) receptor mediated vascular reactivity are uncertain. The aim of this study was to test the hypothesis that dietary modification of TxA(2) levels alters vascular responsiveness to TxA(2) analogues. Juvenile female white pigs were fed a diet enriched in either 5% (w/w) fish oil or beef tallow for 6 weeks. Serum and myocardial tissue levels of eicosapentaenoic and docosahexaenoic acid reached a plateau during this period. Vascular responses were measured in isolated coronary arterial rings with intact endothelium by isometric tension measurement. Arteries from pigs fed fish oil produced a greater maximum vasoconstrictor tension to the TxA(2) analogue U46619 than did rings from pigs fed beef tallow (120 +/- 6% compared to 92 +/- 8%, values represented as a percentage relative to the maximum vasoconstrictor effect obtained to KCl, regression analysis, analysis of variance, P

Factors associated with delay in giving thrombolytic therapy after arrival at hospital.

OBJECTIVE: To identify factors associated with delay in administration of thrombolytic therapy for acute myocardial infarction. DESIGN: Retrospective case note review of a six-month period in 1995. Data were obtained on age, sex, hospital arrival time, triage priority, assessment process in the emergency department, grade of emergency doctor, patient history, timing of and findings on electrocardiogram (ECG), type of infarct, timing and site of administration of thrombolytic therapy, and type of thrombolysis given. SETTING: Tertiary referral hospital in Newcastle, New South Wales. PARTICIPANTS: Eighty-five patients given thrombolytic therapy for acute myocardial infarction. OUTCOME MEASURE: Time between hospital arrival and initiation of thrombolytic therapy. RESULTS: The median time from hospital arrival to administration of thrombolytic therapy was 80 minutes (interquartile range [IR], 50-133). Only 26% of patients were triaged to Priority 1 or 2 (to be seen by a doctor within 10 minutes). Patients initially assessed by a specialist emergency physician received thrombolytic therapy a median of 38 (IR, 33-50) minutes after hospital arrival, compared with 65 (IR, 50-107) minutes if initially assessed by a medical registrar, and 148 (IR, 89-185) and 160 (IR, 95-163) minutes, respectively, if initially assessed by an intern or a resident medical officer (P < 0.001). Factors associated with increased delay in receiving thrombolytic therapy (after adjustment for possible confounders) were low triage priority, initial assessment by a junior doctor, atypical presenting history of myocardial infarction, and lesser degrees of ST-segment elevation on the presenting ECG (all P < or = 0.01). CONCLUSIONS: Delay in administration of thrombolytic therapy in hospital results from a combination of hospital and patient factors. Changes in emergency department protocol may reduce these delays in some patients.

Outcome with calcium channel antagonists after myocardial infarction: a community-based study.

OBJECTIVES: We sought to estimate the risk of death and recurrent myocardial infarction associated with the use of calcium antagonists after myocardial infarction in a population-based cohort study. BACKGROUND: Calcium antagonists are commonly prescribed after myocardial infarction, but their long-term effects are not well established. METHODS: Patients 25 to 69 years old with a suspected myocardial infarction were identified and followed up through a community-based register of myocardial infarction and cardiac death (part of the World Health Organization Monitoring Trends and Determinants in Cardiovascular Disease [MONICA] Project in Newcastle, Australia). Data were collected by review of medical records, in-hospital interview and review of death certificates. RESULTS: From 1989 to 1993, 3,982 patients with a nonfatal suspected myocardial infarction were enrolled in the study. At hospital discharge, 1,001 patients were treated with beta-adrenergic blocking agents, 923 with calcium antagonists, 711 with both beta-blockers and calcium antagonists and 1,346 with neither drug. Compared with patients given beta-blockers, patients given calcium antagonists were more likely to suffer myocardial infarction or cardiac death (adjusted relative risk [RR] 1.4, 95% confidence interval [CI] 1.0 to 1.9), cardiac death (RR 1.6, 95% CI 1.0 to 2.7) and death from all causes (RR 1.7, 95% CI 1.1 to 2.6). Compared with patients given neither beta-blockers nor calcium antagonists, patients given calcium antagonists were not at increased risk of myocardial infarction or cardiac death (RR 1.0, 95% CI 0.8 to 1.3), cardiac death (RR 0.9, 95% CI 0.6 to 1.2) or death from all causes (RR 1.0, 95% CI 0.7 to 1.3). No excess in risk of myocardial infarction or cardiac death was observed among patients taking verapamil (RR 0.9, 95% CI 0.6 to 1.6), diltiazem (RR 1.1, 95% CI 0.8 to 1.4) or nifedipine (RR 1.3, 95% CI 0.7 to 2.2) compared with patients taking neither calcium antagonists nor beta-blockers. CONCLUSIONS: These results are consistent with randomized trial data showing benefit from beta-blockers after myocardial infarction and no effect on the risk of recurrent myocardial infarction and death with the use of calcium antagonists. Comparisons between beta-blockers and calcium antagonists favor beta-blockers because of the beneficial effects of beta-blockers and not because of adverse effects of calcium antagonists.

Effect of phenylephrine infusion on atrial electrophysiological properties.

OBJECTIVE: To determine the effect of changes in autonomic tone induced by phenylephrine infusion on atrial refractoriness and conduction. DESIGN: Left and right atrial electrophysiological properties were measured before and after a constant phenylephrine infusion designed to increase sinus cycle length by 25%. SUBJECTS: 20 patients, aged 53 (SD 6) years, undergoing electrophysiological study for investigation of idiopathic paroxysmal atrial fibrillation (seven patients) or for routine follow up after successful catheter ablation of supraventricular tachycardia (13 patients). MAIN OUTCOME MEASURES: Changes in left and right atrial effective refractory periods, atrial activation times, and frequency of induction of atrial fibrillation. RESULTS: Phenylephrine (mean dose 69 (SD 18) mg/min) increased mean blood pressure by 22 (12) mm Hg (range 7 to 44) and lengthened sinus cycle length by 223 (94) ms (20 to 430). Left atrial effective refractory period lengthened following phenylephrine infusion from 250 (25) to 264 (21) ms (P < 0.001) but there was no significant change in right atrial effective refractory period: 200 (20) v 206 (29), P = 0.11. There was a significant relation between the effect of phenylephrine on sinus cycle length and on right atrial refractoriness (r = 0.6, P = 0.005) with shortening of right atrial refractoriness in patients with the greatest prolongation in sinus cycle length. During phenylephrine infusion, the right atrial stimulus to left atrial activation time at the basic pacing cycle length of 600 ms was unchanged, at 130 (18) v 131 (17) ms, but activation delay with a premature extrastimulus increased: 212 (28) v 227 (38) ms, P = 0.002. Atrial fibrillation was induced by two of 58 refractory period measurements at baseline and by 12 of 61 measurements during phenylephrine infusion (P < 0.01). Phenylephrine increased the difference between left and right atrial refractory periods by 22.8 (19.4) ms in the five patients with induced atrial fibrillation after phenylephrine compared to 0.9 (16.2) ms in the 13 patients without induced atrial fibrillation after phenylephrine infusion (P = 0.02). CONCLUSIONS: Phenylephrine infusion increased left atrial refractoriness and intra-atrial conduction delay following a premature right atrial extrastimulus. Induction of atrial fibrillation during phenylephrine infusion was associated with non-uniform changes in atrial refractoriness. These data support the concept that changes in autonomic tone may precipitate atrial fibrillation in susceptible individuals.

Limited utility of the phenylephrine-nitroprusside sigmoid curve method of measuring baroreflex function after myocardial infarction.

BACKGROUND: Conventional testing of baroreflex function with phenylephrine bolus injection measures reflex vagal tone. OBJECTIVE: To evaluate an alternative pharmacological method of baroreflex testing, which might provide more comprehensive evaluation of the baroreflex function in patients with uncomplicated myocardial infarction. METHODS: Forty-eight patients, aged 59 +/- 7 years, were evaluated 5-7 days after myocardial infarction and after 6 weeks of rehabilitation. Baroreflex testing was performed with 10-14 incremental injections of nitroprusside and phenylephrine. The peak heart rate and blood pressure point from each injection were fitted to a four parameter (upper plateau, lower plateau, gain and median blood pressure) sigmoid logistic function. The baroreflex sensitivity (BRS) was also measured by conventional linear analysis of the response of the R-R interval to the initial rise in systolic blood pressure induced by phenylephrine bolus injection. RESULTS: Non-linear curve fitting of four logistic curve parameters was possible for results from 91% of tests; in the remaining tests the upper plateau was held constant at the maximum heart-rate response to allow estimation of the other three parameters. When all four parameters had been estimated, the gain parameter could not be precisely determined (the coefficient of variation of the gain parameter was 85 +/- 10%). The upper (R = 0.72, P < 0.001) and lower plateaux (R = 0.76, P < 0.001) were strongly related to the resting heart rate and weakly related to measures of heart-rate variability. There was also a significant inverse correlation between the lower plateau and the BRS (R = -0.57, P < 0.001). The gain parameter was not related to the BRS or any measure of the heart-rate variability. After 6 weeks' rehabilitation there was a significant decrease in the lower plateau (from 54 +/- 2 to 48 +/- 1 beats/min, P < 0.001), an increase in BRS (from 9.4 +/- 0.8 to 12.1 +/- 0.8 ms/mmHg, P < 0.001) and no change in the other three sigmoid curve parameters. CONCLUSIONS: Non-linear curve fitting of the heart-rate-blood-pressure relationship for patients after myocardial infarction is feasible but technical limitations and the lack of correlation between the gain parameter and other measures of autonomic function suggest that this method has limited usefulness. The lower plateau is related strongly to the BRS; both are vagal measures of cardiac autonomic function.

Randomized trial of a hospital-based exercise training program after acute myocardial infarction: cardiac autonomic effects.

OBJECTIVES: This study sought to determine whether a moderate intensity supervised exercise training program, performed immediately after an uncomplicated acute myocardial infarction, improves recovery in cardiac autonomic function compared with standard advice about activity at home. BACKGROUND: Exercise training has beneficial effects on cardiac autonomic function and may improve prognosis after acute myocardial infarction. METHODS: Thirty-nine male and 10 female patients, mean (+/-SE) age 57 +/- 1 years, with an uncomplicated acute myocardial infarction were randomized to either a 6-week moderate intensity supervised hospital-based exercise training program (exercise group) or to an unsupervised low intensity home walking program (control group). Outcome measures included changes in baroreflex sensitivity (phenylephrine bolus method) and heart rate variability (24-h Holter monitoring) and the endurance time at 85% of peak oxygen consumption. RESULTS: At baseline, there were no significant differences in left ventricular ejection fraction (57 +/- 2% vs. 53 +/- 2%), frequency of anterior infarction (27% vs. 18%) and peak creatine kinase (1,256 +/- 170 vs. 2,599 +/- 295 IU) between the exercise and control groups. Baroreflex sensitivity (10.5 +/- 1.0 vs. 8.4 +/- 1.2 ms/mm Hg) and time domain measures of heart rate variability were also similar. After completion of the program, the exercise group exercised for a median of 15 min (interquartile range 12 to 25) at a workload of 104 +/- 7 W compared with 7 min (interquartile range 3.5 to 12) at a workload of 89 +/- 8 W in the control group (p < 0.01). There were significant (p < 0.001) improvements in baroreflex sensitivity and heart rate variability for the 49 patients combined but no differences between the exercise and control groups. Baroreflex sensitivity improved by 3.4 +/- 1.0 and 1.7 +/- 1.0 ms/mm Hg and the standard deviation of 24-h RR intervals by 36 +/- 6 and 40 +/- 10 ms, respectively (p > 0.1). CONCLUSIONS: A hospital-based exercise training program increased endurance capacity but did not improve recovery of cardiovascular antonomic function after uncomplicated acute myocardial infarction.

Prevention of cardiac arrhythmia by dietary (n-3) polyunsaturated fatty acids and their mechanism of action.

The role of marine fish oil (n-3) polyunsaturated fatty acids in the prevention of fatal ventricular arrhythmia has been established in experimental animals. Prevention of arrhythmias arising at the onset of ischemia and reperfusion is important because if untreated, they result in sudden cardiac death. Animals supplemented with fish oils in their diet developed little or no ventricular fibrillation after ischemia was induced. Similar effects have also been observed in cultured neonatal cardiomyocytes. Several mechanisms have been proposed and studied to explain the antiarrhythmic effects of fish oil polyunsaturated fatty acids, but to date, no definite mechanism has been validated. The sequence of action of these mechanisms and whether more than one mechanism is involved is also not clear. Some of the mechanisms suggested to explain the antiarrhythmic action of fish oils include the incorporation and modification of cell membrane structure by (n-3) polyunsaturated fatty acids, their direct effect on calcium channels and cardiomyocytes and their role in eicosanoid metabolism. Other mechanisms that are currently being investigated include the role of (n-3) polyunsaturated fatty acids in cell signalling mediated through phosphoinositides and their effect on various enzymes and receptors. This article reviews these mechanisms and the antiarrhythmic studies using (n-3) polyunsaturated fatty acids.

The importance of the left atrioventricular interval during atrioventricular sequential pacing.

During atrioventricular (AV) sequential pacing from the right heart, the interval between the left atrium and ventricle may vary from the programmed AV interval depending on the position of the atrial and ventricular electrodes and interatrial and interventricular conduction. The aim of this study was to determine the hemodynamic effects of altering the left AV interval while keeping the programmed AV interval constant. Four male and 17 female patients, aged 49 +/- 15 years were studied. The left AV interval was measured by a catheter in the coronary sinus. Stroke volume and mitral flow were measured by simultaneous echo Doppler during AV sequential pacing from the right atrial appendage and right ventricular apex at programmed AV intervals of 100, 60, and 6 ms. The atrial catheter was then positioned on the atrial septum and the measurements repeated. With the atrial catheter in the right atrial appendage, interatrial activation time (118 +/- 20 ms) was similar to interventricular activation time (125 +/- 21 ms) and the left AV interval was almost identical to the programmed right AV interval. There was a significant correlation between interatrial and interventricular activation times (r = 0.8; P < 0.001). Positioning the atrial electrode on the septum decreased interatrial activation time by 39 +/- 12 ms and increased the left AV interval by a similar amount. At a programmed AV interval of 60 ms, the left AV interval increased from 67 +/- 15 ms to 105 +/- 17 ms after the atrial catheter was repositioned from the appendage to the septum (P < 0.001). Compared to pacing from the right atrial appendage, atrial septal pacing increased mitral A wave velocity integral (2.8 +/- 1.4 vs 4.4 +/- 1.7 cm at a programmed AV interval of 60 ms, P < 0.01), decreased E wave velocity integral (8.1 +/- 2.2 vs 6.1 +/- 2.4 cm, P < 0.001) but did not alter stroke volume (44.8 +/- 10.6 vs 44.9 +/- 10.1 mL). In contrast, a 40 ms decrease in the programmed right AV interval from 100 to 60 ms decreased stroke volume from 48.0 +/- 10.0 to 44.9 +/- 10.2 mL (P < 0.001). There was a strong relationship between interatrial and interventricular conduction so that patients with prolonged interatrial conduction still had equivalent left and right AV intervals during atrioventricular sequential pacing from the right atrial appendage and right ventricular apex. Positioning the atrial electrode on the septum decreases interatrial activation time and increases the left AV interval by about 40 ms but has minimal hemodynamic effect in patients without heart failure.

Sotalol proarrhythmia: a report of five cases and an audit of the use of a sotalol in a teaching hospital.

BACKGROUND: Polymorphic ventricular tachycardia is an uncommon complication of sotalol use. AIMS: The aims of this study were: (1) to report five cases of sotalol proarrhythmia and (2) to audit the use of sotalol in a teaching hospital population. METHODS: Five patients with sotalol proarrhythmia (defined as new ventricular arrhythmias associated with sotalol administration) were identified over an 18 month period. Sotalol use for patients admitted to the John Hunter Hospital was audited over a six month period with 85 patients (55 males) identified from the pharmacy database. Medical records were reviewed and the details of treatment including sotalol dose and indication determined. Creatinine clearance was estimated by the Cockcroft and Gault regression equation. RESULTS: The audit indicated that sotalol was prescribed predominantly for management of atrial arrhythmias (80%). Paroxysmal atrial fibrillation was the most common indication (71%). Although female patients were older (72 +/- 13 vs 62 +/- 15 years, p < 0.001) and had a lower creatinine clearance (55 +/- = 24 vs 82 +/- = 32 mg/minute, p < 0.001) than male patients, they were prescribed similar doses of sotalol (206 +/- 112 vs 193 +/- 93 mg/day). The ratio of sotalol dose to creatinine clearance was higher in female patients (4.0 +/- 2.6 vs 2.16 +/- 1.5, p < 0.01). The five patients with proarrhythmia (torsades de pointes in four patients and polymorphic ventricular tachycardia in one patient) were all female. Daily sotalol dose (odds ratio for each 160 mg tablet 4.9 [95% confidence interval 1.5-16] and female gender (p < 0.01) were significant risk factors for proarrhythmia. CONCLUSION: Sotalol dose was not appropriately adjusted for creatinine clearance which is age and gender dependent. Female patients have an increased risk of proarrhythmia and should receive lower doses of sotalol.

Cardiac event recorders yield more diagnoses and are more cost-effective than 48-hour Holter monitoring in patients with palpitations. A controlled clinical trial.

OBJECTIVE: To compare the diagnostic yield and cost-effectiveness of transtelephonic event monitors with those of Holter monitoring in patients with intermittent palpitations. DESIGN: Randomized crossover trial. SETTING: Diagnostic service of a teaching hospital and surrounding primary care practices. PATIENTS: 43 patients with previously uninvestigated palpitations who were referred for Holter monitoring. MEASUREMENTS: Patients were randomly allocated to receive an event monitor or 48-hour Holter monitor and then to receive the other device. Event monitors were used for 3 months or until two recordings were obtained while symptoms occurred. The main end point was an electrogram recorded during symptoms. The incremental cost-effectiveness of obtaining a diagnostic rhythm strip from event monitors was compared with that of Holter monitoring. RESULTS: The mean (+/- SD) patient age was 45 +/- 19 years; 37 patients (88%) were women. Event monitors were twice as likely to provide a diagnostic rhythm strip electrocardiogram during symptoms as 48-hour Holter monitoring (29 patients [67%] and 15 patients [35%], respectively; P < 0.001). Event monitors detected 8 patients (19%) with clinically important arrhythmias (6 patients with supraventricular tachycardia and 2 with atrial fibrillation or flutter), whereas the Holter monitors detected no significant arrhythmia (P < 0.005). With the event monitors, most patients transmitted an electrocardiogram recording by 6 weeks. Event monitors were dominant and therefore more cost-effective than 48-hour Holter monitoring, resulting in a cost savings of $213 for each additional diagnostic rhythm strip obtained during symptoms. CONCLUSIONS: Holter monitoring is a poor diagnostic test for intermittent palpitations. Event recorders provide better data and are more cost-effective.

Long-term reproducibility of ventricular tachycardia induction in patients with implantable cardioverter/defibrillators. Serial noninvasive studies.

BACKGROUND: Noninvasive electrophysiological studies (EPSs) can be performed in current implantable antitachycardia pacemaker/cardioverter/defibrillators (ICDs). Thus, these devices may be used as tools to study changes in the electrophysiological substrate and ventricular tachycardia characteristics over time. METHODS AND RESULTS: Fifty-five patients receiving an ICD for treatment of sustained ventricular tachyarrhythmias underwent serial EPSs after implantation of the ICD. Studies were performed before hospital discharge and 1, 3, 5, 9, 12, 18, 24, and 36 months after ICD implantation. Sustained monomorphic ventricular tachycardia (VT) was induced in 37 patients (group 1) at the predischarge EPS, whereas no sustained arrhythmia could be induced in 18 patients (group 2) at baseline. Group 1 patients underwent 165 noninvasive EPSs after discharge. Sustained monomorphic VT was induced during 72% of the follow-up EPSs, ventricular fibrillation (VF) was induced during 11% of follow-up EPSs, and no sustained VT or VF was induced during 17% of follow-up visits. Sustained VT was induced at every follow-up EPS in 23 patients (62%), whereas no sustained VT/VF could be induced at least once during follow-up in 14 patients (38%). Clinical or electrophysiological variables did not predict noninducibility during follow-up. However, the probability that a patient would experience spontaneous VT decreased significantly over time in patients in whom VT was not inducible during at least 1 follow-up EPS (P = .05). Group 2 patients underwent 86 noninvasive EPSs after discharge. Sustained monomorphic VT was induced during 22% of follow-up EPSs, VF was induced during 19% of follow-up EPSs, and no sustained VT/VF could be induced during 68% of follow-up EPSs. No sustained VT/VF could be induced during every follow-up EPS in 9 patients (50%), whereas sustained monomorphic VT was induced at least once during follow-up in 7 patients (34%). Persistent noninducibility of VT during follow-up was associated with low probability of occurrence of spontaneous VT (11%), whereas inducibility of VT at least once during follow-up was associated with the occurrence of spontaneous VT (89%, P = .003). CONCLUSIONS: Considerable variability of VT induction is observed over a lengthy period in patients presenting with sustained VT/VF. Persistent noninducibility of VT is associated with a reduced probability of spontaneous VT. These observations suggest that the substrates for inducible and spontaneous VT change in parallel over time.

Upward bias in estimates of pacemaker reliability: effect of unreported patient mortality.

OBJECTIVES: This study attempted to determine the effect of unreported patient deaths on estimates of pacemaker reliability. BACKGROUND: The reliability of pacemakers is usually reported with reference to implant registration data and returned product analysis without censoring when follow-up data are missing. METHODS: We studied 73 patients (mean [+/- SD] age 77 +/- 8 years) undergoing implantation of a ventricular-inhibited (VVI) pacemaker who were subsequently found to be at increased risk of experiencing premature pacemaker failure. Survival curves for patients and pacemakers were constructed by the Kaplan-Meier method with appropriate censoring at the time of unrelated death or elective explantation of a normal device. To examine the effect of unreported loss of follow-up data, patient mortality was then ignored, and follow-up for pacemakers without known failure was assumed to continue to the date of analysis. RESULTS: There were 13 device failures, with a median pacemaker survival time of 37 months. Twenty-three patients died, all of causes unrelated to the pacemaker system; median patient survival time was only 44 months. Ignoring this attrition inflated follow-up time from 122 to 188 patient-years and reduced the apparent pacemaker failures at 30 months by almost half, from 37% to only 20%. Modeling the process shows that when the patient mortality rate is more than half the pacemaker failure rate, ignoring censoring inflates the device survival estimate by > or = 10% from the median survival onward. CONCLUSIONS: When medical device survival curves are generated by implant registration data and returned product analysis, they should be adjusted for unreported loss of follow-up.

The inefficacy of intravenous propafenone for rate control in atrial fibrillation.

The antiarrhythmic agent propafenone has been reported to prolong atrioventricular node conduction and may be suitable for rate control in atrial fibrillation (AF). To evaluate this, 10 patients (seven men and three women aged 29 to 67 years, mean +/- SD 48 +/- 14) were given intravenous propafenone during AF in both the supine and upright positions. Intracardiac catheters measured local electrograms from the high right atrium and right ventricular apex during AF. Atrial rate, ventricular rate and blood pressure were recorded in the control state and after head-up tilt with these measurements repeated after propafenone 1.5 mg/kg was infused over 5 mins. Four of 10 patients reverted to sinus rhythm. Propafenone increased the mean ventricular cycle length (496 +/- 147 versus 556 +/- 152 ms, P = 0.1), although this did not reach significance. In contrast, propafenone markedly increased the mean atrial cycle length (136 +/- 35 versus 226 +/- 39, P < 0.001). The mean ventricular cycle length reverted to baseline after tilt (447 +/- 103 ms) while the mean atrial cycle length decreased but not to baseline levels (170 +/- 21 ms). The authors conclude that intravenous propafenone is generally inadequate for rate control in AF, especially in the upright position.

VDD pacing at short atrioventricular intervals does not improve cardiac output in patients with dilated heart failure.

Atrial synchronous pacing with short, nonphysiological atrioventricular (AV) intervals has been reported to increase cardiac output in selected patients with severe dilated heart failure. The aim of this study was to determine the acute effect of atrial synchronous pacing with short AV intervals in a consecutive series of patients with dilated heart failure. Twelve patients with a mean ejection fraction of 21% +/- standard error 2.5% were studied. Pacing catheters were placed in the high right atrium and right ventricular apex and a balloon flotation catheter in the pulmonary artery for measurement of cardiac output. Simultaneous transthoracic echocardiography was performed for measurement of left ventricular filling time and mitral regurgitation. In a randomized crossover design, measurements were made during VDD pacing at programmed AV intervals of 100 and 60 msec and during a control period in sinus rhythm. Left ventricular filling time increased at AV intervals of 100 and 60 msec (mean difference 37 +/- 9 and 34 +/- 11 msec, respectively, both P < 0.01 compared to control). Despite increases in ventricular filling time, stroke, and cardiac index declined with short atrioventricular intervals (at an AV interval of 60 msec, stroke index fell by 2.1 +/- 0.5 mL/m2, P < 0.05 and cardiac index by 125 +/- 45 mL/m2; P = NS). Heart rate was unchanged at both AV intervals (78 +/- 4.9 at control, 78 +/- 5.2 at 100 msec and 79 +/- 4.9 beats/min at 60 msec; P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

A placebo-controlled trial of intravenous and oral disopyramide for prevention of neurally mediated syncope induced by head-up tilt.

OBJECTIVES: A double-blind randomized trial was designed to determine the efficacy of intravenous and oral disopyramide phosphate in preventing neurally mediated syncope induced by a head-up tilt test. BACKGROUND: Neurally mediated syncope is a frequent cause of syncope and may be induced by head-up tilt testing. Recent uncontrolled trials have suggested that disopyramide may be an effective therapy in patients with neurally mediated syncope. METHODS: Twenty-two consecutive patients with recurrent neurally mediated syncope and two or more successive positive head-up tilt test responses were randomly allocated to receive either intravenous disopyramide or placebo. Head-up tilt testing at 60 degrees was performed for 15 min. If presyncope or syncope was not provoked, isoproterenol infusion was started at a rate of 1 microgram/min and the rate gradually increased until a 25% increase in heart rate was achieved. Eleven patients were subsequently randomized in crossover fashion to receive oral disopyramide (800 mg/day) or placebo during 1 week. The primary end point was prevention of syncope or presyncope provoked by head-up tilt testing. RESULTS: Head-up tilt test results were positive for syncope in 12 (75%) of 16 patients receiving intravenous placebo and in 12 (60%) of 20 patients receiving disopyramide (p = 0.55 Fisher exact test, 95% confidence interval [CI] -14% to 40%). In the intravenous phase, complete crossover was achieved in 15 patients. Head-up tilt test results during this phase were positive in 13 patients (87%) receiving placebo and in 12 patients (80%) receiving disopyramide (p = 0.50 Fisher exact test, 95% CI -19% to 32%) and were positive in all patients receiving their initially randomized drug or placebo. In the oral phase, head-up tilt results were positive in only two patients (18%) assigned to placebo and in three patients (27%) receiving disopyramide (p = 0.54 Fisher exact test, 95% CI -42% to 24%). A mean follow-up time of 29 +/- 8 months was obtained in 21 of the 22 patients. Syncope recurred in 3 (27%) of the 11 patients receiving disopyramide and 3 (30%) of the 10 patients not treated pharmacologically (p > 0.05). CONCLUSIONS: Intravenous disopyramide was ineffective for the prevention of neurally mediated syncope provoked by head-up tilt testing. No significant effect was observed after oral therapy with disopyramide. There was a striking decrease in the incidence of positive tilt test results over time regardless of intervention, thus discouraging the use of head-up tilt as the single method of assessing therapeutic efficacy. Recurrence of syncope after the investigative protocol was infrequent over long-term follow-up regardless of treatment group.

A prospective randomized comparison of autodecremental pacing to burst pacing in device therapy for chronic ventricular tachycardia secondary to coronary artery disease.

A number of modes of antitachycardia pacing therapies are available in the newer generations of implantable cardioverter/defibrillators. The efficacy of synchronized burst overdrive pacing for the termination of induced and spontaneous monomorphic ventricular tachycardia (VT) was compared with synchronized autodecremental (ramp) pacing in 21 patients who received an implantable antitachycardia pacemaker/cardioverter/defibrillator for treatment of recurrent sustained monomorphic VT. Patients undergoing serial noninvasive VT induction studies after device implantation were prospectively randomized to receive trials of burst or ramp pacing therapies in a crossover study design. Antitachycardia pacing therapies were equally efficacious in treating induced VT (68% for ramp, 76% for burst pacing trials). The efficacy of ramp (93%) and burst (96%) pacing therapies was significantly higher in terminating spontaneously occurring episodes of VT than in terminating induced episodes (p = 0.001). The incidence of tachycardia acceleration was similar for both modes of pacing. The incidence of VT acceleration was lower for spontaneously occurring episodes of VT (0.01%) than for induced episodes of VT (6%, p < 0.01). Thus, antitachycardia pacing is an effective therapy for episodes of monomorphic VT, and the risk of accelerating VT to a hemodynamically unstable form is low. Antitachycardia pacing therapies are more effective against spontaneously occurring episodes than induced episodes of VT. Differences in tachycardia cycle length and duration may contribute to these effects.

Predictors of defibrillation efficacy in patients undergoing epicardial defibrillator implantation. The Multicenter Pacemaker-Cardioverter-Defibrillator (PCD) Investigators Group.

OBJECTIVES: The objective of this study was to identify predictors of defibrillation threshold in patients undergoing epicardial defibrillator implantation. BACKGROUND: Factors that predict epicardial defibrillation efficacy are poorly defined. METHODS: The data from 375 consecutive adult patients were reviewed. After exclusion of 137 patients in whom defibrillation threshold was not obtained, 238 patients (32 women and 206 men) with a mean age of 58.9 +/- 13.3 years formed the study group. Coronary heart disease was present in 175 patients and the mean left ventricular ejection fraction was 35.8 +/- 15.4%. At device implantation, three epicardial patch sizes were available and shocks could be delivered over one current pathway (two patches) or over two current pathways (three patches with simultaneous or sequential shocks). Defibrillation threshold was defined as the lowest programmed energy that successfully defibrillated the heart, provided there had been an unsuccessful shock at a lower energy level or successful defibrillation at < or = 5 J. RESULTS: The mean defibrillation threshold was 8.6 +/- 5.3 J. With univariate analysis, female gender, sequential shocks with three patches, higher left ventricular ejection fraction and lower New York Heart Association functional class predicted a lower defibrillation threshold. In the multivariate analysis, female gender (coefficient -3.9; 95% confidence interval [CI] -1.9 to -5.0 J), ejection fraction (coefficient -0.6; CI -0.1 to -1.0 J/decile) and sequential shocks (coefficient -2.5; CI -1.0 to -4.0 J) were independently associated with a lower defibrillation threshold. Total epicardial patch conductive surface area normalized to body surface area reached borderline significance (coefficient 0.004; CI 0 to 0.01; p = 0.10). Antiarrhythmic drug use, including amiodarone, did not predict defibrillation threshold. CONCLUSIONS: Female gender, high left ventricular ejection fraction and the use of sequential pulse shocks were important determinants of improved defibrillation efficacy.

A unique preexcitation pattern related to an atypical anteroseptal accessory pathway.

Accessory atrioventricular pathways have traditionally been classified by anatomical location to four areas, namely anteroseptal, posteroseptal, and right and left free walls. Each of these have been associated with a relatively distinct preexicitation pattern electrocardiographically. We describe a patient with a unique ECG pattern suggesting preexicitation to the right ventricular outflow region. Preoperative and intraoperative electrophysiological testing confirmed the presence of an accessory pathway with an atrial insertion site near the His bundle, decremental anterograde conduction, and a ventricular insertion site in the upper part of the interventricular septum. Operative ablation near the atrial insertion site eliminated preexicitation.

Effect of atropine and isoproterenol on tachycardia induction in asymptomatic patients with Wolff-Parkinson-White electrocardiographic pattern.

OBJECTIVE: To determine if pharmacological interventions aimed at altering autonomic tone would allow induction of orthodromic atrioventricular reentrant tachycardia in asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern. DESIGN: Prospective interventional protocol in consecutive eligible patients. SETTINGS: University hospital. PATIENTS: Eighteen asymptomatic patients (13 male and five female) with the Wolff-Parkinson-White electrocardiographic pattern without inducible tachycardia in the drug-free state. INTERVENTION: Electrophysiological assessment was performed at baseline, after intravenous administration of atropine (0.03 mg/kg) and during isoproterenol infusion (0.5 to 2 micrograms/min). RESULTS: Orthodromic reciprocating tachycardia was not inducible at baseline because of absent retrograde accessory pathway conduction in seven patients. In five patients, orthodromic atrial echo beats could be induced (which blocked retrogradely in the accessory pathway in three patients and anterogradely in the atrioventricular node in two). In the remaining six patients, neither orthodromic echo beats nor reciprocating tachycardia could be induced despite intact retrograde accessory pathway conduction. Following atropine administration (mean dose 1.9 +/- 0.3 mg), anterograde and retrograde accessory pathway effective refractory periods decreased from 360 +/- 172 to 284 +/- 62 ms and from 340 +/- 38 to 296 +/- 32 ms, respectively (both P < 0.05 versus control). Orthodromic reciprocating tachycardia was induced in two patients (nonsustained in one). During isoproterenol infusion (mean dose 1.0 +/- 0.3 micrograms/min), anterograde and retrograde accessory pathway effective refractory periods decreased further to 243 +/- 23 and 248 +/- 22 ms, respectively (both P < 0.05 versus after atropine); two further patients had inducible orthodromic reciprocating tachycardia (nonsustained in one). No patient with absent retrograde accessory pathway conduction developed retrograde accessory pathway conduction or reciprocating tachycardia with isoproterenol and/or atropine. CONCLUSIONS: Isoproterenol and/or atropine allowed tachycardia induction in four of 18 asymptomatic patients with the Wolff-Parkinson-White electrocardiographic pattern. In the majority of these patients, tachycardia is not inducible because of deficient retrograde accessory pathway conduction which does not improve with autonomic facilitation.