Use of medications in Wolff-Parkinson-White syndrome.

The diagnosis of Wolff-Parkinson-White syndrome is generally straightforward; however, the management may not be, and requires an understanding of the competing risks of various treatment options and that of the clinical setting in which the diagnosis is made. The symptomatic patient with Wolff-Parkinson-White has an increased risk of atrial fibrillation and a small but significant risk of sudden cardiac death. Therapy is based on reduction in symptom burden and attenuation of the risk of pre-excited atrial fibrillation. Catheter ablation is the most effective means of achieving this goal with abolition of symptoms and risk of pre-excited atrial fibrillation. Medication is often employed in the acute setting to terminate paroxysms of arrhythmia associated with the accessory pathway and reduce the subsequent burden of symptoms until ablation can be performed. An overview of the agents commonly used is provided together with recommendations.

Use of the implantable loop recorder in patients with unexplained syncope.

Syncope is a complex clinical syndrome with multiple etiologies that can be very difficult to diagnose. The major obstacles to diagnosis are the periodic and unpredictable nature of events and the high spontaneous remission rate. Conventional testing is often unproductive in patients when initial non-invasive testing is negative, particularly when a paroxysmal ar-rhythmia is suspected. Holter monitoring is often employed initially, with limited utility. Holter monitoring provides a rhythm profile, but rarely achieves the gold standard of a symptom rhythm correlation. The external loop re-corder extends the period of monitoring, enhancing the diagnostic yield to as high as 60% in patients with symptoms likely to recur during a month of device use. Finally, implantable loop recorders further extend the ability to monitor cardiac patients, enhancing the diagnostic yield to as high as 85% in difficult to diagnose syncope. Several recent studies suggest that prolonged monitoring with an implantable loop recorder has a role in patients with syncope and conduction disturbances, negative tilt testing, unexplained seizures and may be superior to conventional testing with tilt and electrophysiologic studies in select patients.

A randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of intravenously administered dofetilide in patients with Wolff-Parkinson-White syndrome.

Pharmacological conversion of arrhythmias in Wolff-Parkinson-White (WPW) syndrome is often frequently undertaken. Current antiarrhythmic drugs used for conversion can be associated with significant side effects and variable efficacy. Fifteen male patients (mean age 34, range 18-63 years) with WPW syndrome and atrial fibrillation or AVRT induced in the electrophysiology laboratory were enrolled in a prospective, randomized, placebo-controlled crossover study. Patients were randomized to one of two doses of intravenous dofetilide or placebo. Patients who failed to respond to this initial infusion received a second higher dose infusion of dofetilide. With the initial infusion, six of ten dofetilide patients converted to sinus rhythm compared to one of five placebo patients. After a second infusion of dofetilide for placebo patients and higher dose dofetilide for low dose dofetilide patients, the overall conversion rate was 71% with dofetilide compared with 20% for placebo (P = 0.046). Atrial fibrillation converted to sinus rhythm in 82% of patients who received dofetilide. Intravenous dofetilide was safe and effective at converting induced atrial fibrillation in patients with WPW syndrome.

Safety and feasibility of a novel rate-smoothed ventricular pacing algorithm for atrial fibrillation.

OBJECTIVES: This study was conducted to establish the safety and performance of a new rate-smoothing pacing algorithm for patients with atrial fibrillation (AF). BACKGROUND: Irregularity of the ventricular response is a hallmark of AF. This irregularity may contribute to symptoms and hemodynamic compromise in patients with AF. Interventions designed to reduce irregularity have not previously been evaluated in a long-term, clinical setting. METHODS: We designed a prospective, double-blind study with randomized crossover. Patients with either paroxysmal or chronic AF whose conditions were medically refractory and who were referred for an atrioventricular node ablation procedure all underwent pacemaker implantation. Subjects were then randomly assigned to either DDD mode with the rate-smoothing algorithm (RSA) on, or to OOO mode. After 2 months they were crossed over to the other arm. RESULTS: Fourteen patients (9 with paroxysmal AF and 5 with chronic AF) were enrolled. There were no significant differences between the group randomly assigned to RSA first versus the group assigned to OOO first. The mean left ventricular ejection fraction with the RSA was not significantly different than it was in OOO mode (45.1 +/- 18.6 vs 51.9 +/- 12.3; P =.11), although some individuals with uncontrolled ventricular rates did have a large decrease in ejection fraction with rate smoothing. One developed overt heart failure. One quality-of-life instrument detected a significant improvement in the "physical limitations" domain with the rate-smoothing mode. Eleven of 14 patients preferred the RSA ON arm, and 6 of those 11 elected to defer the ablation procedure. CONCLUSIONS: Long-term rate-smoothed pacing is feasible. Because of concerns about pacing-induced heart failure in some patients with rapid ventricular rates, rate-smoothed pacing should be reserved for those who remain symptomatic despite adequate control of the ventricular rate. The RSA may help to reduce symptoms in patients with medically refractory AF; more study is required to define its efficacy in reducing symptoms and morbidity in this population.

Randomized assessment of syncope trial: conventional diagnostic testing versus a prolonged monitoring strategy.

BACKGROUND: Establishing a diagnosis in patients with unexplained syncope is complicated by infrequent and unpredictable events. Prolonged monitoring may be an alternative strategy to conventional testing with short-term monitoring and provocative tilt and electrophysiological testing. METHODS AND RESULTS: Sixty patients (aged 66+/-14 years, 33 male) with unexplained syncope were randomized to "conventional" testing with an external loop recorder and tilt and electrophysiological testing or to prolonged monitoring with an implantable loop recorder with 1 year of monitoring. If patients remained undiagnosed after their assigned strategy, they were offered crossover to the alternate strategy. A diagnosis was obtained in 14 of 27 patients randomized to prolonged monitoring compared with 6 of 30 patients undergoing conventional testing (52% versus 20%, P=0.012). Crossover was associated with a diagnosis in 1 of 6 patients undergoing conventional testing compared with 8 of 13 patients who completed monitoring (17% versus 62%, P=0.069). Overall, prolonged monitoring was more likely to result in a diagnosis than was conventional testing (55% versus 19%, P=0.0014). Bradycardia was detected in 14 patients undergoing monitoring compared with 3 patients undergoing conventional testing (40% versus 8%, P=0.005). CONCLUSIONS: A prolonged monitoring strategy is more likely to provide a diagnosis than conventional testing in patients with unexplained syncope. Consideration should be given to earlier implementation of a monitoring strategy.

Progression to chronic atrial fibrillation after pacing: the Canadian Trial of Physiologic Pacing. CTOPP Investigators.

OBJECTIVES: This study examined the effect of physiologic pacing on the development of chronic atrial fibrillation (CAF) in the Canadian Trial Of Physiologic Pacing (CTOPP). BACKGROUND: The role of physiologic pacing to prevent CAF remains unclear. Small randomized studies have suggested a benefit for patients with sick sinus syndrome. No data from a large randomized trial are available. METHODS: The CTOPP randomized patients undergoing first pacemaker implant to ventricular-based or physiologic pacing (AAI or DDD). Patients who were prospectively found to have persistent atrial fibrillation (AF) lasting greater than or equal to one week were defined as having CAF. Kaplan-Meier plots for the development of CAF were compared by log-rank test. The effect of baseline variables on the benefit of physiologic pacing was evaluated by Cox proportional hazards modeling. RESULTS: Physiologic pacing reduced the development of CAF by 27.1%, from 3.84% per year to 2.8% per year (p = 0.016). Three clinical factors predicted the development of CAF: age > or =74 years (p = 0.057), sinoatrial (SA) node disease (p < 0.001) and prior AF (p < 0.001). Subgroup analysis demonstrated a trend for patients with no history of myocardial infarction or coronary disease (p = 0.09) as well as apparently normal left ventricular function (p = 0.11) to derive greatest benefit. CONCLUSIONS: Physiologic pacing reduces the annual rate of development of chronic AF in patients undergoing first pacemaker implant. Age > or =74 years, SA node disease and prior AF predicted the development of CAF. Patients with structurally normal hearts appear to derive greatest benefits.

Should patients with asymptomatic wolff-parkinson-white pattern undergo a catheter ablation?

Many individuals with the Wolff-Parkinson-White electrocardiographic pattern are asymptomatic. Optimal management of these individuals is still a matter of debate. On the one hand, sudden cardiac death from ventricular fibrillation is a rare yet possible outcome in these individuals. On the other hand, there is a low risk of serious complication from electrophysiologic study and ablation. Given that the risk of these competing strategies is comparable, the decision needs to be individualized with considerable patient input.

Predictive value of presyncope in patients monitored for assessment of syncope.

BACKGROUND: The purpose of this study was to assess the diagnostic value of recording the cardiac rhythm during presyncope in patients undergoing monitoring for undiagnosed syncope. METHODS AND RESULTS: Eighty-five patients (age, 59 +/- 18 years; 44 men, 41 women) with recurrent unexplained syncope underwent prolonged monitoring with an implantable loop recorder. Patients were examined for syncope, which was either recurrent or associated with at least 2 presyncopal episodes. Patients had a mean of 5.1 +/- 5.5 syncopal episodes in the previous 12 months, and 70% of patients had symptoms for >2 years. Sixty-two (73%) patients had recurrent symptoms during a 12-month follow-up period. Of 150 recurrent events captured by the implantable loop recorder, there were 38 (25%) episodes of syncope and 112 (75%) episodes of presyncope. Syncope alone recurred in 12 patients, presyncope in 25, and both in 16. An arrhythmia was present in 64% of syncopal events (bradycardia in 16, tachycardia in 2) versus 25% for presyncopal events (bradycardia in 7, tachycardia in 3, P =.001). An arrhythmia was detected in 9 (56%) of the 16 patients with both syncope and presyncope, which was present in all recorded episodes of syncope compared with 6 of 9 presyncopal episodes. Patient-related failure to freeze the device after symptoms occurred in 21 (36%) of 59 syncopal events compared with 15 (12%) of 127 presyncopal events (P =.0001). CONCLUSIONS: Syncope is more likely to be associated with an arrhythmia than is presyncope in patients undergoing extended monitoring. Presyncope is a nonspecific end point that is frequently associated with sinus rhythm. Patients undergoing extended monitoring for syncope should continue to be monitored after an episode of presyncope unless an arrhythmia is detected.

Supraventricular tachycardia.

Supraventricular tachycardias (SVT) comprise those tachycardias that originate above the bifurcation of the bundle of His. They can be classified broadly as AV node dependent and AV node independent. The mechanism and clinical manifestation of SVTs, which is essential to their correct diagnosis, is reviewed. The therapeutic management of SVTs, including acute and chronic drug therapy and catheter ablation, is discussed also.

QT dispersion: an electrocardiographic derivative of QT prolongation.

BACKGROUND: QT dispersion has been considered a surrogate for heterogeneity of repolarization, leading to ventricular arrhythmias. METHODS: High-resolution 12-lead electrocardiograms were obtained in 15 patients with a history of ventricular tachycardia or ventricular fibrillation, 15 patients with congestive heart failure, 17 patients with a history of previous Q-wave myocardial infarction without heart failure, and 23 healthy control subjects. RESULTS: QTc dispersion was prolonged in all 3 patient groups compared with controls (71+/-22, 68 +/-31, 61+/-27 vs 44+/-17 msec, P =. 003), but no difference was seen between heart disease groups. QTc dispersion was strongly correlated with the QTc max (r = 0.73, P<.0001) but did not correlate with the QTc min (r = 0.04, P =.76). QTc dispersion also strongly correlated with the JTc max (r = 0.54, P<.0001) but did not correlate with JTc min (r = -0.007, P =.95). QTc dispersion correlated inversely with T-wave amplitude (r = -0.35, P =.003). When all 876 electrocardiographic signals were considered, a significant negative correlation was present between QTc duration and T-wave amplitude (r = -0.133, P =.0002). Logistic regression analysis failed to demonstrate any independent risk factors that predicted ventricular arrhythmias, including all measures of dispersion. CONCLUSIONS: The measurement of QT dispersion is strongly influenced by the maximum QT interval, as well as by changes in T-wave amplitude. QT "dispersion" may represent a summary of these changes that reflect the underlying myocardial process but does not represent an accurate quantitative measure of heterogeneity of refractoriness.

Rate-control versus conversion strategy in postoperative atrial fibrillation: a prospective, randomized pilot study.

BACKGROUND: Atrial fibrillation remains a frequent complication after heart surgery. The optimal strategy to treat the condition has not been established. Several retrospective studies have suggested that a primary rate-control strategy may be equivalent to a strategy that restores sinus rhythm. METHODS: Fifty patients with atrial fibrillation after heart surgery were randomly assigned to a strategy of antiarrhythmic therapy with or without electrical cardioversion or ventricular rate control. Both arms received anticoagulation with heparin overlapped with warfarin. The primary end point was time to conversion to sinus rhythm analyzed by the Kaplan-Meier method. Atrial fibrillation relapse after the initial conversion was monitored in the hospital over a 2-month period. RESULTS: There was no significant difference between an antiarrhythmic conversion strategy (n = 27) and a rate-control strategy (n = 23) in time to conversion to sinus rhythm (11.2 +/- 3. 2 vs 11.8 +/- 3.9 hours; P =.8). With the use of Cox multivariate analysis to control for the effects of age, sex, beta-blocker usage, and type of surgery, the antiarrhythmic strategy showed a trend toward reducing the time from treatment to restoration of sinus rhythm (P =.08). The length of hospital stay was reduced in the antiarrhythmic arm compared with the rate-control strategy (9.0 +/- 0.7 vs 13.2 +/- 2.0 days; P =.05). In-hospital relapse rates in the antiarrhythmic arm were 30% compared with 57% in the rate-control strategy (P =.24). There were no significant difference in relapse rates at 1 week (24% vs 28%), 4 weeks (6% vs 12%), and 6 to 8 weeks (4% vs 9%). At the end of the study, 91% of the patients in the rate-control arm were in sinus rhythm compared with 96% in the antiarrhythmic arm (P =.6). CONCLUSIONS: This pilot study shows little difference between a rate-control strategy and a strategy to restore sinus rhythm. Regardless of strategy, most patients will be in sinus rhythm after 2 months. A larger randomized, controlled study is needed to assess the impact of restoration of sinus rhythm on length of stay.

Impact of a mandatory physician reporting system for cardiac patients potentially unfit to drive.

CONTEXT: Sudden cardiac incapacitation of a driver may lead to the death or serious injury of passengers or bystanders. This has raised public safety concerns and has led to the creation of legislation to protect the public. Some jurisdictions in Canada and the United States have introduced mandatory physician reporting of patients who may be unfit to drive for medical reasons. The impact on motor vehicle accident (MVA)-related morbidity and mortality of mandatory physician reporting for at-risk cardiac patients is unknown. OBJECTIVE: To determine the impact of mandatory physician reporting legislation (for cardiac patients) in Ontario (population 10.3 million) on MVA-related morbidity and mortality. DATA SOURCES: Reporting data were obtained from the Ontario Ministry of Transportation. Incidence and prevalence data were taken from Ontario Ministry of Health sources and from the literature (MEDLINE). Data for modelling were taken from the literature (MEDLINE) and from the Canadian Cardiovascular Society's Consensus Conference document on cardiac illness and fitness to drive. DATA EXTRACTION: Licence suspension data (correlated with medical illness) were taken directly from government documents. These were then applied to a 'risk of harm' formula used to calculate the risk posed to bystanders and passengers by the suspended patients if they had continued to drive. Canadian licence suspension guidelines were then reviewed in conjunction with cardiac disease incidence and prevalence data to arrive at the number of patients who should have been suspended. Physician compliance with the legislation was then calculated, along with the potential impact on MVA-related morbidity and mortality in the scenario of 100% physician compliance. STUDY SELECTION: All Ontario drivers who had licence suspensions in 1996 for reasons of cardiac disease were included in the analysis. DATA SYNTHESIS: Nine hundred and ninety-four licences were suspended for cardiac reasons in 1996, compared with an estimated 72,407 that should have been suspended if Canadian guidelines had been followed (1.4%). Less than one death or serious injury was avoided as a result of the legislation (from the 'risk of harm' formula). If all drivers with cardiac illness had been suspended from driving, up to 29.2 such events could potentially have been avoided. However, only 13 of 929 (1.4%) road fatalities in Ontario in 1996 were attributed to a driver with a medical illness. CONCLUSIONS: Mandatory physician reporting of patients with cardiac illness has a negligible impact on MVA-related morbidity and mortality.

List-mode maximum-likelihood reconstruction applied to positron emission mammography (PEM) with irregular sampling.

We present a preliminary study of list-mode likelihood reconstruction of images for a rectangular positron emission tomograph (PET) specifically designed to image the human breast. The prospective device consists of small arrays of scintillation crystals for which depth of interaction is estimated. Except in very rare instances, the number of annihilation events detected is expected to be far less than the number of distinguishable events. If one were to histogram the acquired data, most histogram bins would remain vacant. Therefore, it seems natural to investigate the efficacy of processing events one at a time rather than processing the data in histogram format. From a reconstruction perspective, the new tomograph presents a challenge in that the rectangular geometry leads to irregular radial and angular sampling, and the field of view extends completely to the detector faces. Simulations are presented that indicate that the proposed tomograph can detect 8-mm-diameter spherical tumors with a tumor-to-background tracer density ratio of 3:1 using realistic image acquisition parameters. Spherical tumors of 4-mm diameter are near the limit of detectability with the image acquisition parameters used. Expressions are presented to estimate the loss of image contrast due to Compton scattering.

Recurrent seizure diagnosed by the insertable loop recorder.

INTRODUCTION: The Insertable Loop Recorder (ILR) has emerged as an important new tool in the diagnostic armamentarium for patients with syncope. METHODS AND RESULTS: A case report illustrates how the ILR unexpectedly led to the diagnosis of seizure as the explanation for a man's recurrent, but infrequent episodes of sudden loss of consciousness. CONCLUSIONS: This case raises the possibility that the development of implantable recording devices which monitor physiologic parameters other than cardiac rhythm (eg. brain, nerve or muscle activity) may provide the long-term monitoring capability needed to improve the diagnostic yield for conditions, such as seizures, which occur infrequently.

A novel mutation in KVLQT1, L122P, found in a family with autosomal dominant long QT syndrome.

BACKGROUND: Linkage and mutation analysis in long QT syndrome kindreds has demonstrated locus heterogeneity, with causative mutations reported in at least 5 different genes, including KVLQT1. METHODS AND RESULTS: A 12-year-old male proband with recurrent syncope and a prolonged QT interval underwent clinical assessment and exercise testing along with 3 affected and 3 unaffected family members. The coding regions of 5 putative transmembrane segments (S2-S6) and a putative pore region of the KVLQT1 gene for the proband were amplified with the polymerase chain reaction. DNA sequencing of the KVLQT1 gene of the proband revealed a T-->C transversion at the second position of codon 122, which predicted a substitution of proline for leucine (L122P). By using restriction analysis, the L122P was found to be co-segregated with the electrocardiographic abnormalities in the nuclear family. Although the patient's mother was heterozygous for L122P, neither maternal grandparent was a carrier, suggesting that the mutation arose spontaneously. In comparison, there was a complete absence of the mutation in 1336 alleles from 668 normal individuals of 6 different ethnic backgrounds. CONCLUSION: The KVLQT1 L122P mutation is a rare novel mutation that probably arose spontaneously in this family, leading to long QT syndrome.