Telangiectasias of the breasts showing diffuse dermal angiomatosis in a patient with diffuse livedo reticularis.

The breasts are a common location for diffuse dermal angiomatosis (DDA) in a context of obesity and macromastia. The typical clinical presentation includes erythematous or purplish plaques, reticulated telangiectasias, and sometimes livedo reticularis, often complicated by painful ulcerations of the breasts. Biopsy usually confirms a dermal proliferation of endothelial cells staining positively for CD31, CD34 and SMAa and negatively for HHV8. We report herein a woman with DDA of the breasts presenting as diffuse livedo reticularis and acrocyanosis, both long-standing and considered idiopathic following extensive investigations. Since a biopsy of the livedo did not document DDA features in our case, we suggest that our patient's livedo reticularis and telangiectasias could constitute a vascular predisposition for DDA, as its pathogenesis frequently involves an underlying disease involving ischemia, hypoxia, or hypercoagulability.

Reverse atrial electrical remodelling following atrial defibrillation as determined by signal-averaged ECG.

BACKGROUND: Following successful cardioversion for atrial fibrillation (AF), the rate of early recurrence remains high. Analysis of the signal-averaged electrocardiogram of the P wave has been proposed as a noninvasive method of predicting those at risk of recurrence. PURPOSE: To determine the change in signal-averaged P wave duration (SAPWD) following cardioversion from AF, and to determine whether SAPWD is associated with the risk of recurrence. METHODS: SAPWD was determined in 76 patients immediately following successful electrical cardioversion and three days later. Patients were then followed clinically for one year. RESULTS: Recurrent AF was observed in 32 of 76 patients at 90 days following cardioversion. There was no difference in SAPWD immediately following cardioversion (158+/-28 ms versus 164+/-31 ms, P=NS) or three days following cardioversion (152+/-24 ms versus 158+/-36 ms, P=0.4) in patients with and without recurrent AF. There was, however, a significant decrease in the SAPWD during the first three days following cardioversion in the patients who remained in sinus rhythm (158+/-28 ms initially versus 152+/-24 ms on day three, P=0.009). Among the patients with recurrent AF, the decrease was smaller and not statistically significant (161+/-30 ms versus 158+/-36 ms, P=0.3). CONCLUSION: Shortening of the SAPWD occurs following atrial defibrillation in patients who maintain sinus rhythm at 90 days. This provides evidence for reverse atrial electrical remodelling and its association with the maintenance of sinus rhythm.

Antiarrhythmic drug therapy in the Multicenter UnSustained Tachycardia Trial (MUSTT): drug testing and as-treated analysis.

OBJECTIVES: Using data from the Multicenter UnSustained Tachycardia Trial (MUSTT), we examined the factors used to select antiarrhythmic drug therapy and their impact on outcomes. BACKGROUND: The MUSTT examined the use of programmed ventricular stimulation (PVS) to guide antiarrhythmic therapy in patients with coronary arteriosclerosis, left ventricular dysfunction and asymptomatic, unsustained ventricular tachycardia (VT). Trial outcomes may reflect factors used to select antiarrhythmic drug therapy. METHODS: We compared subgroups of patients with inducible sustained VT randomized to PVS-guided antiarrhythmic therapy (n = 351), in particular those receiving PVS-guided antiarrhythmic drug therapy (n = 142) versus no antiarrhythmic therapy (controls, n = 353). RESULTS: "Effective" antiarrhythmic drug therapy (i.e., the term "effective" was used to denote therapy that resulted in noninducible VT or hemodynamically stable induced VT) was found for 142 of the 351 patients (43%), most often at the first or second PVS session (125/142, 88%). Mortality among the 142 patients did not differ from that among control patients. Of these 142 patients, the PVS end point was noninducibility in 91 patients and stable VT in 51 patients. Mortality did not differ between these two groups either, but arrhythmia was numerically more frequent in the PVS-induced stable VT group. Mortality was greatest in the few patients receiving propafenone (unadjusted p = 0.07, adjusted p = 0.14 vs. controls), but mortality with all agents did not differ from that of controls, even after adjustment. CONCLUSIONS: Even when presenting the results as favorably as possible, we found no benefit with PVS-guided drug therapy in patients with clinical unsustained VT who had inducible sustained VT. These findings are unaltered by using different end points for PVS or considering the response to individual drugs.

Initial clinical experience with ambulatory use of an implantable atrial defibrillator for conversion of atrial fibrillation. Metrix Investigators.

BACKGROUND: A recent study has shown that the implantable atrial defibrillator can restore sinus rhythm in patients with recurrent atrial fibrillation when therapy was delivered under physician observation. The objective of this study was to evaluate the safety and efficacy of ambulatory use of the implantable atrial defibrillator. METHODS AND RESULTS: An atrial defibrillator was implanted in 105 patients (75 men; mean age, 59+/-12 years) with recurrent, symptomatic, drug-refractory atrial fibrillation. After successful 3-month testing, patients could transition to ambulatory delivery of shock therapy. Patients completed questionnaires regarding shock therapy discomfort and therapy satisfaction using a 10-point visual-analog scale (1 represented "not at all," 10 represented "extremely") after each treated episode of atrial fibrillation. During a mean follow-up of 11.7 months, 48 of 105 patients satisfied criteria for transition and received therapy for 275 episodes of atrial fibrillation. Overall shock therapy efficacy was 90% with 1.6+/-1.2 shocks delivered per episode (median, 1). Patients rated shock discomfort as 5.2+/-2.4 for successful therapy and 4.2+/-2.2 for unsuccessful therapy (P:>0.05). The satisfaction score was higher for successful versus unsuccessful therapy (3.4+/-3. 3 versus 8.7+/-1.3, P:<0.05). There was no ventricular proarrhythmia observed throughout the course of this study. CONCLUSIONS: Ambulatory use of an implantable atrial defibrillator can safely and successfully convert most episodes of atrial fibrillation, often requiring only a single shock. Successful therapy is associated with high satisfaction and only moderate discomfort.

Evaluation of outpatient initiation of antiarrhythmic drug therapy in patients reverting to sinus rhythm after an episode of atrial fibrillation.

The safety of a method of outpatient antiarrhythmic drug loading utilizing a continuous loop event recorder was evaluated. The findings suggest that the standard 2-day hospital admission for drug loading is not necessary in all patients and a method of outpatient loading may be equally safe.

Atrial pacing leads following open heart surgery: active or passive fixation?

The right atrial appendage is often amputated at the time of cardiopulmonary bypass. Because of concerns regarding lead displacement, use of active fixation atrial leads has been recommended in patients who require permanent atrial or dual chamber pacing after open heart surgery. We evaluated the acute and chronic performance of active and passive fixation atrial leads implanted at our institution between 1985 and 1993 in patients with previous open heart surgery. Of 78 consecutive patients, 38 had an active fixation atrial lead, 28 had a passive fixation steroid-eluting lead, and 12 had a passive fixation lead without steroid-eluting properties. At implantation, sensed P wave amplitudes were similar in the three groups, but lead impedance and threshold were significantly higher for active fixation leads compared to all passive fixation leads. During follow-up, atrial pacing thresholds were significantly higher, and sensed P wave amplitudes significantly lower, in the patients with active fixation leads compared to those with passive fixation leads. Loss of sensing occurred in 6 of 38 (16%) patients with active fixation leads and 1 of 40 (2.5%) patients with a passive fixation lead (P = 0.027). Atrial lead displacement occurred in two patients with active fixation leads and one with a passive fixation lead. Comparison with a parallel group of patients without previous open heart surgery demonstrated that atrial lead performance was similar in the two groups. We conclude that, when permanent atrial or dual chamber pacing is necessary in patients with prior open heart surgery, it is appropriate to implant a passive fixation atrial lead except on the infrequent occasions when a stable atrial position cannot be obtained.

Cost savings with nonthoracotomy implantable cardioverter-defibrillators.

We analyzed hospital and physician charges for 99 consecutive patients who underwent implantable cardioverter-defibrillator (ICD) implantation at our institution. Eighteen patients received an epicardial lead system and 81 were scheduled to receive a nonthoracotomy lead system, the generator being implanted either abdominally (n = 62) or pectorally (n = 19). The epicardial group had a significantly longer convalescent stay (11.6 +/- 2.5 days; mean +/- SEM) than the abdominal nonthoracotomy group, analyzed by intention to treat (4.6 +/- 0.5 days) or by treatment received (3.8 +/- 0.2 days; p <0.0001). Postoperative stay for the pectoral group was shorter still (2.9 +/- 0.4 days; p <0.033). Total charges for the epicardial group were $99,081 +/- $25,094, significantly higher than those for any of the nonthoracotomy groups (p <0.017). Total charges for the pectoral group were $44,128 +/- $2,465, significantly less than those for the abdominal nonthoracotomy group, analyzed by intention to treat ($59,961 +/- $1,369; p <0.05) or by treatment received ($56,679 +/- $635; p <0.05). Cost reductions in the nonthoracotomy groups were primarily due to decreased in-hospital convalescence period, lower surgeon and anesthesiologist fees, and lower procedure-day hospital charges in the pectoral group. The use of ICDs with nonthoracotomy leads can result in significantly shorter in-hospital convalescence and a reduction in total implant-related charges of 40% to 55%. The use of pectorally implanted ICDs results in further reduction in hospital stay and further cost reduction of 22% to 26%. The trend toward shorter convalescent stay without postimplant testing is likely to reduce further the overall costs of ICD implantation.

Initial experience with an implantable hemodynamic monitor.

BACKGROUND: Measurement of intracardiac hemodynamic parameters has been limited to brief periods in the acute care setting. We developed and evaluated an implantable hemodynamic monitor that is capable of measuring chronic right ventricular oxygen saturation and pulmonary artery pressure. METHODS AND RESULTS: The device consists of an electronic controller placed subcutaneously and two transvenous leads placed in the right ventricle (reflectance oximeter) and pulmonary artery (variable capacitance pressure sensor). Implantation was performed in 10 patients with severe left ventricular dysfunction. Average implant pulmonary artery pressures were systolic, 52 +/- 16 mm Hg; diastolic, 29 +/- 11 mm Hg; and mean, 40 +/- 12 mm Hg. The mean right ventricular oxygen saturation at implant was 51%. Provocative maneuvers, including postural changes, sublingual nitroglycerin, and bicycle exercise, demonstrated expected changes in measured oxygen saturation and pulmonary artery pressures over time. At follow-up of 0.5 to 15.5 months, there were no significant differences between pulmonary artery pressures or oxygen saturation values transmitted from the device and simultaneous measurement with balloon flotation catheters. Four of the pulmonary artery leads dislodged and three demonstrated sensor drift, whereas two of the oxygen saturation sensors failed. Four patients died and four received transplants. Pathological study did not demonstrate injury to the right ventricular outflow tract or pulmonic valve. CONCLUSIONS: Chronic measurement of hemodynamic parameters in the outpatient setting with implantable sensor technology appears to be feasible. The devices are well tolerated without significant untoward effects, and the sensors generally function well over time, providing reliable information. Clinical usefulness remains to be established.

Catheter ablation using radiofrequency or low-energy direct current in pediatric patients with the Wolff-Parkinson-White syndrome.

Percutaneous ablation of accessory pathways was performed in 22 consecutive children and adolescents (9 boys and 13 girls, age range 8 to 18 years). Low-energy direct current (DC) was used exclusively in the first 6 patients, whereas ablation was performed with radiofrequency energy in the following 16. Accessory pathways were located in the left free wall in 15 patients, were posteroseptal in 3, were in the right free wall in 3 and were anteroseptal in 1. A concealed accessory pathway was present in 7 patients (32%). There was no significant difference in clinical or electrophysiologic variables between both groups. Catheter ablation was successful in the initial 6 patients using low-energy DC, as compared with 13 of 16 patients using radiofrequency ablation. Low-energy DC was successful as a backup power source in all 3 patients who had unsuccessful radiofrequency ablation. There was no complication. The median procedural and fluoroscopic times for successful ablation were 2.5 hours and 49 minutes, respectively (p = NS between both power sources). Accessory pathway conduction recurred in 2 patients (33%) who had low-energy DC as compared with 1 (6%) who had radiofrequency ablation (p = NS). These 3 patients had successful reablation of their accessory pathways. In children and adolescents with accessory pathways, both new power sources compare favorably, with an overall success rate of ablation of 100% (22 of 22 patients). Radiofrequency ablation should be used initially because it does not require general anesthesia and is associated with a lower rate of recurrence of accessory pathway conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Results of a comparative study of low energy direct current with radiofrequency ablation in patients with the Wolff-Parkinson-White syndrome.

OBJECTIVE: To compare two new power sources for catheter ablation in patients with the Wolff-Parkinson-White syndrome. DESIGN: 120 consecutive patients with accessory pathways had catheter ablation. Low energy direct current (DC) was used in the first 60 patients and radio-frequency current in the next 60 patients. SETTING: Electrophysiological laboratory of a large heart institute. PATIENTS: 72 men and 48 women (mean (SD) age 35 (14) years (range 9-75)). The accessory pathways were in the left free wall in 73 patients. They were posteroseptal in 35 patients, in the right free wall in five, and anteroseptal in seven. There was no significant difference in the clinical or electrophysiological variables between the two ablation groups. RESULTS: Catheter ablation with low energy direct current was successful in 55/60 patients (92%) and radiofrequency energy was successful in 52/60 patients (87%). Low energy direct current was also successful in four of the eight patients in whom radiofrequency ablation had failed. Radiofrequency ablation was successful in two of the five patients in whom low energy direct current ablation had failed. The mean (SD) procedure and fluoroscopy times for successful ablation were 3.2 (1.5) h and 61 (40) min respectively. These times were similar for both power sources. Accessory pathway conduction recurred in 17 patients (28%) who had low energy direct current and four patients (7%) who received radiofrequency energy (p < 0.004). All patients with recurrence of an accessory pathway had successful re-ablation. CONCLUSIONS: Both new power sources successfully ablated accessory pathways, (overall success rate 94% (113/120 patients)). Radiofrequency ablation, however, did not require general anaesthesia and was associated with a significantly lower rate of recurrence of accessory pathway conduction. Therefore radiofrequency should be used initially for ablation. Low energy direct current may be most useful as a back-up in patients in whom radiofrequency ablation fails.

Rate-dependent effects of diltiazem on human atrioventricular nodal properties.

BACKGROUND: Tachycardia enhances the channel-blocking effects of antiarrhythmic drugs. In contrast to the extensive data regarding the rate-dependent effects of sodium channel blockers in humans, little is known about the frequency-dependent effects of calcium channel blockers on human atrioventricular (AV) nodal properties. Accordingly, the purpose of this study was to evaluate the importance of heart rate in modulating the electrophysiological effects of diltiazem in humans. METHODS AND RESULTS: Electrophysiological studies were performed in 25 patients. Sinus node, atrial, and AV nodal function were evaluated at multiple atrial rates under control conditions and after administration of one of three intravenous doses of diltiazem designed to produce low, intermediate, and high stable plasma concentrations (designated doses 1, 2, and 3, respectively). Results were analyzed in terms of the longest and shortest cycle lengths obtainable in each patient under control and drug conditions. Plasma concentrations of diltiazem were stable and averaged 43 +/- 4, 73 +/- 6, and 136 +/- 11 ng/ml for doses 1, 2, and 3, respectively. Sinus node recovery time, intra-atrial conduction time, atrial effective refractory period, and HV interval were unaffected by diltiazem infusion. Effects of diltiazem were limited to changes in AV nodal parameters. Stable, dose-dependent increases in Wenckebach cycle length were observed after all three doses of diltiazem (increases of 54 +/- 13, 84 +/- 18, and 174 +/- 33 msec for doses 1, 2, and 3, respectively). Small nonsignificant increases in AH interval and atrioventricular effective refractory period (AVERP) were observed after dose 1 of diltiazem. At long cycle lengths, diltiazem caused modest increases in AH interval (3 +/- 4 and 25 +/- 8 msec for doses 2 and 3, respectively) and AVERP (36 +/- 12 and 70 +/- 25 msec). Drug effects were far greater at short cycle lengths (45 +/- 17 msec, 58 +/- 12 msec for AH interval and 80 +/- 24 msec, 163 +/- 41 msec for AVERP; p less than 0.05 versus values at long cycle lengths). At rapid rates, effects of diltiazem on AVERP substantially exceeded those on AV conduction, a result that could account for the beneficial effects of diltiazem during paroxysmal AV reentrant tachycardia by decreasing the excitable gap. CONCLUSIONS: Depressant effects of diltiazem on human AV nodal function are highly dependent on atrial rate; the rate-dependent actions on AV nodal refractoriness probably contribute to beneficial effects of diltiazem in patients with supraventricular arrhythmias.

Prognosis in rupture of the ventricular septum after acute myocardial infarction and role of early surgical intervention.

Since 1944, 91 patients (50 men and 41 women, mean age 68 years [range 39 to 86]) with ventricular septal rupture after acute myocardial infarction were seen at the Mayo Clinic. Patients were divided into 4 groups according to therapy and timing of surgical intervention. Fourteen patients seen before 1965, when surgery was not performed for such a complication or not readily available, were excluded from the analysis. Group 1 (n = 22) had surgery within 48 hours of septal rupture, group 2 (n = 6) underwent operation between 2 and 14 days, group 3 (n = 24) had surgery after 14 days, and group 4 (n = 25) only received medical treatment. Short-term (30 days) survivors (45%, 35 of 77 patients) were compared with nonsurvivors. Using logistic regression, by univariate analysis, 3 variables were significantly associated with outcome: age (p less than 0.01), cardiogenic shock (p less than 0.00001), and long delay between ventricular septal rupture and surgical intervention (p less than 0.004). By multivariate analysis, however, only cardiogenic shock (p less than 0.00001) and age (p less than 0.007) correlated with an adverse outcome. In patients with cardiogenic shock after septal rupture, the prognosis was uniformly fatal unless patients undergo early surgery. None of the 23 patients in groups 2, 3 or 4 survived, whereas 5 of 13 patients (38%) who had surgery within 48 hours of septal rupture survived.(ABSTRACT TRUNCATED AT 250 WORDS)

Success, safety, and late electrophysiological outcome of low-energy direct-current ablation in patients with the Wolff-Parkinson-White syndrome.

BACKGROUND: Percutaneous ablation of accessory pathways with the use of a defibrillator can be accomplished with high-energy direct-current (DC) shocks of 150-400 J, but complications include cardiac tamponade and sudden cardiac death, mostly resulting from significant electrical arcing and barotrauma. A new low-energy DC power source with a brief time-constant capacitive discharge delivers shocks of 2-40 J and eliminates or greatly reduces arcing. This report describes our initial experience with this device in 60 consecutive patients (mean age, 34 years; range, 9-67 years) with Wolff-Parkinson-White syndrome. Accessory pathways were located in the left free wall in 36 patients, in the right free wall in two, were posteroseptal in 18, and anteroseptal in four. Most patients (77%) had their initial diagnostic electrophysiological study and catheter ablation during the same session. METHODS AND RESULTS: Selective ablation of accessory pathways was successful in 55 patients (92%). The mean cumulative energy was 312 +/- 284 J and the mean creatine kinase MB peak (normal, 0-30 units) was 42 +/- 27 units. Patients with left free wall accessory pathways required less procedure time for ablation (2.7 +/- 0.8 versus 3.6 +/- 1.5 hours, p less than 0.0007) and less fluoroscopy time (46 +/- 24 versus 66 +/- 33 minutes, p less than 0.002). Complications were limited to transient pericarditis (three patients), one iliac artery dissection, and cardiac tamponade probably caused by catheter repositioning in the coronary sinus (one patient). An electrophysiological study was repeated in 50 of the 55 successful cases at a mean of 9 +/- 5 months. This study was normal in 48 of 50 (96%) patients. CONCLUSIONS: Low-energy DC ablation is safe and effective treatment for accessory pathways in children and adults. The long-term outcome is excellent as documented by electrophysiological restudy.

Sudden arrhythmic death without overt heart disease.

Nine patients (eight males) are reported with one or more episodes of circulatory collapse in the absence of overt heart disease or other known causes of arrhythmias; sudden arrhythmic death occurred in one of these patients. Age at first episode ranged from 16 to 41 (mean, 28) years. In seven patients, ventricular fibrillation was documented at the time of resuscitation. One patient had ventricular flutter. In the remaining patient, documentation of the arrhythmia during the collapse was not available. Four patients had frequent early ventricular premature beats, and in three of these patients, they were accompanied by episodes of rapid nonsustained polymorphic ventricular tachycardia. Failure to suppress this ectopic activity by drug therapy seems to be of prognostic significance. Of the three patients showing persistence of frequent early ventricular premature beats, one died suddenly, and two had recurrences of symptomatic arrhythmic episodes. The value of noninvasive and invasive tests in the management of these patients is not clear, with the exception of exercise testing in patients with exercise-related arrhythmias and long-term electrocardiographic monitoring in patients with frequent spontaneous ventricular ectopic activity. Follow-up varied from 21 to 192 (mean, 84) months. One patient died suddenly 21 months after his first collapse. Selection of antiarrhythmic drug therapy was largely empirical. In view of the relative rarity of sudden arrhythmic death in the absence of heart disease and the many uncertainties about its mechanism(s) and management, a worldwide registry of these patients is suggested.

Low energy direct current ablation in patients with the Wolff-Parkinson-White syndrome: clinical outcome according to accessory pathway location.

Forty-five patients with the Wolff-Parkinson-White syndrome underwent direct current (DC) ablation using a low energy power source (Cardiac Recorders). Anodal shocks of 10-40 joules were given to either a 6 French quadripolar catheter (Bard), a 7 French bipolar contoured catheter (Bard), or a 7 French deflectable catheter with a 4-mm distal electrode (Mansfield). The indifferent electrode consisted of a large patch that was positioned under the left scapula. There were 26 males and 19 females, with a mean age of 34 years (range 9-67). Accessory pathways were located in the left free wall in 30 patients (67%) and were posteroseptal in 15 patients (33%). The shortest ventriculoatrial interval during mapping (89 +/- 21 msec), the mean cumulative amount of energy per patient (322 +/- 283 joules), and the mean CK-MB rise (45 +/- 30 units, normal 0-30 units) were not significantly different between both groups. Ablation was successful in 29/30 patients (97%) with a left free-wall accessory pathway, and in 13/15 patients (87%) with a posteroseptal accessory pathway. All three patients with failure of ablation had multiple accessory pathways, and two of these patients had Ebstein's anomaly. Patients with left free-wall and posteroseptal accessory pathways, respectively, differed significantly in terms of: total session time (4.1 +/- 1 hours vs 5.3 +/- 1.3, p = 0.0001), total procedure time for ablation (2.6 +/- 0.8 hours vs 3.2 +/- 1.2, P = 0.02), and fluoroscopy time (46 +/- 24 min vs 64 +/- 29, P = 0.006). In 13 patients (29%) with a concealed accessory pathway, these variables were not significantly different from patients with overt preexcitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Physical and dynamic characteristics of DC ablation in relation to the type of energy delivery and catheter design.

We evaluated and compared the in vitro characteristics of direct current ablation using high energy ablation (Hewlett-Packard defibrillator) and a new form of low energy ablation (low energy ablation power supply, Cardiac Recorders, UK). Two new catheters with a large distal electrode have been recently introduced for catheter ablation: a low energy 7F bipolar catheter (Bard) with a contoured distal electrode, and a 7F deflectable catheter with a 4-mm tip (Mansfield). In vitro studies were carried out in a large tank filled with physiological saline while recording voltage, current, and pressure. High speed cinematography at 32,000 frames per second (Cordin, Utah) was done to assess the dynamic behavior of the vapor globe with both systems of energy delivery. We evaluated shocks of 50, 100, 150, 200, and 300 joules with the conventional system, and shocks of 10, 15, 20, 30, and 40 joules with the new system, and also compared the effects of varying catheter design with both systems of energy delivery. The conventional system using high energy showed significant arcing and increases in pressure. Low energy direct current ablation produces nonarcing shocks with 20 joules or less, and significantly less vapor globe and gas formation during arcing shocks, with a shorter duration of increase in pressure. This new system using low energy direct current may reduce the risk and complications reported with high energy ablations.

Kinetics of use-dependent ventricular conduction slowing by antiarrhythmic drugs in humans.

BACKGROUND: Rate-dependent conduction slowing by class I antiarrhythmic agents has clinically important consequences. Class I drugs are known to produce use-dependent sodium channel blockade. If rate-dependent conduction slowing by class I agents is due to sodium channel blocking actions, the kinetics of conduction slowing should be similar to those of depression of sodium current indexes in vitro. The purpose of the present investigation was to study the onset time course of ventricular conduction slowing caused by a variety of class I agents in humans. METHODS AND RESULTS: Twenty-seven patients undergoing electrophysiological evaluation for antiarrhythmic therapy were studied. Changes in QRS duration at initiation of ventricular pacing at cycle lengths of 400 and 500 msec were used to evaluate the kinetics of drug action. Mean time constants for each drug were similar to values for Vmax depression reported in vitro studies: flecainide, 24.9 +/- 11.6 beats in eight patients (versus 34.5 beats reported for Vmax block); propafenone, 17.8 +/- 6.9 beats in five patients (versus 8.4-20.8 beats); quinidine, 7.0 +/- 2.4 beats in six patients (versus 5.6-6.2 beats); and amiodarone, 3.6 +/- 2.0 beats for eight patients (versus 3.0 beats). Time constants were significantly different among the various drugs tested (p = 0.0002 at a cycle length of 400 msec; p = 0.002 at 500 msec), and there was a strong correlation (r = 0.89, p less than 0.0001) between values obtained at a cycle length of 400 msec and those at a cycle length of 500 msec. No rate-dependent changes in QRS duration were seen at onset of ventricular pacing among eight age- and disease-matched control patients not taking class I antiarrhythmic drugs, including three patients subsequently showing such changes during type I antiarrhythmic drug therapy. CONCLUSIONS: We conclude that class I agents produce use-dependent QRS prolongation in humans with characteristic kinetics for each agent that are similar to the kinetics of Vmax depression in vitro. These results suggest that rate-dependent ventricular conduction slowing by antiarrhythmic drugs in humans is due to use-dependent sodium channel blockade.

Atrial fibrillation in patients with an accessory pathway: importance of the conduction properties of the accessory pathway.

To investigate how the electrophysiologic properties of the accessory pathway affect the occurrence of atrial fibrillation in the Wolff-Parkinson-White syndrome, programmed stimulation data of 57 patients with overt pre-excitation and 33 patients with a concealed accessory pathway with documented circus movement tachycardia were reviewed. Atrial fibrillation had occurred spontaneously in 31 (54%) of the 57 patients with the Wolff-Parkinson-White syndrome and in 1 (3%) of the 33 with a concealed accessory pathway (p less than 0.001). Sustained atrial fibrillation was induced in 23 of 31 patients with the Wolff-Parkinson-White syndrome and spontaneous atrial fibrillation (Group A), in 7 of 26 patients with the Wolff-Parkinson-White syndrome without spontaneous atrial fibrillation (Group B) and in 5 of 33 patients with a concealed accessory pathway (Group C). The anterograde effective refractory period of the accessory pathway was shorter in Group A than in Group B (252 versus 297 ms, p less than 0.001). There were no differences among groups in PA interval, right to left atrium conduction time, cycle length of tachycardia and atrial and retrograde accessory pathway effective refractory period. Atrial fibrillation is more frequent in patients with the Wolff-Parkinson-White syndrome than in those with a concealed accessory pathway. Patients with overt pre-excitation and atrial fibrillation have a shorter anterograde accessory pathway refractory period. It seems therefore that the anterograde rather than the retrograde conduction properties of the accessory pathway are the critical determinants of atrial fibrillation in the Wolff-Parkinson-White syndrome.

Electrophysiologic evaluation and outcome of patients with syncope of unknown origin.

Electrophysiologic studies were performed in 134 patients (87 males, mean age 59 years) with unexplained syncope. Seventy-one patients had organic heart disease (ischaemic in 50). Electrophysiologic studies revealed conduction abnormalities and tachyarrhythmias that could account for syncope in 40 patients (30%). Thirty-seven (93%) of these patients received pacing or antiarrhythmic therapy compared with 23 (24%) of the remaining 94 patients who had a negative study and received empiric therapy (P less than 0.0001). Risk of having an abnormal electrophysiologic study was greater in patients with underlying heart disease (P less than 0.05). During a mean follow-up of 22 +/- 17 months, 26 patients (19%) either had recurrent syncope (22 patients) or died (four patients) suddenly. Men had a higher incidence of recurrent syncope than women (26% vs 6%, P less than 0.005). Other clinical characteristics, electrophysiologic findings, final diagnosis and therapy at discharge were not predictive of outcome. We conclude that (1) 19% of patients investigated for syncope will have a recurrent event, (2) female gender may be an independent predictor of favourable outcome.