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Biomedical subjects

Mark E Josephson

Publications and source records attributed to Mark E Josephson.

At least 19 recordsLinked to original sources
PubMed2006

Atrioventricular nodal reentrant tachycardia associated with idiopathic ventricular tachycardia: clinical and electrophysiologic characteristics.

BACKGROUND: Case reports have described the coexistence of ventricular tachycardia (VT) and supraventricular tachycardia in the same patient. This study examines the frequency of dual atrioventricular nodal (AVN) physiology, AVN echo beats, and atrioventricular nodal reentrant tachycardia (AVNRT) in patients with VT. METHODS: Programmed atrial and ventricular stimulation was performed in 132 consecutive patients referred for electrophysiologic study of symptomatic VT. Of the 132, 99 patients had structural heart disease, and 33 patients had idiopathic ventricular tachycardia (IVT). RESULTS: Among the 33 patients with IVT, 23 had dual AVN physiology. Compared with patients with structural heart disease undergoing VT ablation, dual AVN pathways (70% vs 27%, P < .0001), dual AVN pathways with echo beats (24% vs 8%, P = 0.03), and AVNRT (21% vs 1%, P = .0002) were more common in patients with IVT. CONCLUSION: Dual AVN physiology and AVNRT appear to be associated with IVT. This finding suggests that patients with IVT should undergo a complete electrophysiologic evaluation, and the diagnosis of coexistent AVNRT should be considered in this population.

Adolescent↗
PubMed2006

Frequency and causes of implantable cardioverter-defibrillator therapies: is device therapy proarrhythmic?

Implantable cardioverter-defibrillator (ICD) shocks diminish patients' quality of life, increase health care resource utilization, and may lead to other adverse sequelae. Better understanding of the factors that lead to ICD therapies, and better strategies to avoid unnecessary therapies, are needed to optimize patient outcomes. Data from major randomized clinical trials involving the use of ICDs and cardiac resynchronization therapy-defibrillator devices were reviewed to determine control group mortality rates, control group sudden death rates, and the frequency of appropriate and inappropriate ICD therapies. In all studies that classified deaths, appropriate ICD therapies outnumbered control group sudden cardiac deaths by a factor of 2 to 3. Some of these episodes can be explained by device programming, by the treatment of potentially unsustained tachycardias, and by errors of episode classification. Another underexplored possibility is that device therapy is proarrhythmic. Reasons for frequent therapies and methods to prevent them are discussed, as well as the notion of device proarrhythmia and the potentially detrimental effects of ICD shocks. These issues clearly affect the overall benefit of device therapy and have important implications for patient management and health care delivery.

Arrhythmias, Cardiac↗
PubMed2006

Patterns and predictors of warfarin use in patients with new-onset atrial fibrillation from the FRACTAL Registry.

Warfarin is underused for stroke prevention in atrial fibrillation (AF). Previous studies addressing this have lacked longitudinal assessment. This study sought to characterize contemporary warfarin use in new-onset AF and evaluate its change over time. It was hypothesized that AF recurrence has an important influence on warfarin use patterns. One thousand five adults from 17 centers in the United States and Canada were enrolled into a prospective observational registry after their first documented episodes of AF. Detailed demographic, clinical history, and management data were collected on all subjects at enrollment, including medication use. Patients were followed at regular intervals for interim events and changes in AF management. Warfarin use at baseline and last follow-up (mean 25 +/- 8 months) after enrollment was modeled using multivariate analysis. Initially, 65% of subjects were prescribed warfarin, but only 44% were taking it at 30 months. Even in "ideal" candidates for warfarin, the rate of warfarin prescription decreased from 70% at baseline to 50% at 30 months. Stroke risk factors, including hypertension, congestive heart failure, valvular heart disease, and previous stroke or transient ischemic attack were significant predictors of warfarin prescription at baseline. At last follow-up, the relation between AF recurrence and warfarin use (odds ratio 2.3, 95% confidence interval 1.6 to 3.1) was stronger than that for any individual stroke risk factor. In conclusion, predictors of warfarin use in patients with AF include AF recurrence and selected stroke risk factors. The discontinuation of warfarin in a large number of patients with AF over time is a cause for concern in light of data from recent clinical trials.

Aged↗
PubMed2006

Variation in pulmonary vein size during the cardiac cycle: implications for non-electrocardiogram-gated imaging.

BACKGROUND: Understanding pulmonary vein (PV) anatomy is important for the planning and execution of PV isolation for the treatment of atrial fibrillation, screening for PV stenosis after the procedure, and investigating the pathophysiology of atrial fibrillation. We hypothesized that significant changes in PV size occur during the cardiac cycle and sought to identify the relationship of data obtained with conventional non-electrocardiogram (ECG)-gated methods compared with ECG-gated measures of PV size using cardiovascular magnetic resonance. METHODS: A consecutive series of 14 patients in sinus rhythm were evaluated with non-ECG-gated contrast-enhanced magnetic resonance angiography and ECG-gated cine cardiovascular magnetic resonance of the PV. Pulmonary vein diameter, perimeter, and cross-sectional area (CSA) were measured using both methods. RESULTS: Maximum diameter, perimeter, and CSA occurred simultaneously in all PV. The timing of the maximum size varied but generally occurred in ventricular diastole (101 +/- 112 milliseconds after mitral valve opening). The timing of minimum PV size also varied but generally occurred in ventricular systole (212 +/- 90 milliseconds before mitral valve opening). The difference between the maximum and minimum PV size was 15% +/- 8% for diameter, 15% +/- 7% for perimeter, and 27% +/- 12% for CSA (P < .001 for all). Contrast-enhanced magnetic resonance angiography correlated best with the ECG-gated maximum PV size (R2 > 0.48, P < .001 for all) and was greater than the minimum and average PV sizes (P < .05 for all). CONCLUSIONS: All measures of PV size vary significantly during the cardiac cycle. Contrast-enhanced magnetic resonance angiography PV measurements correlate best with maximum PV size.

Adult↗
PubMed2006

Characterization of the infarct substrate and ventricular tachycardia circuits with noncontact unipolar mapping in a porcine model of myocardial infarction.

BACKGROUND: Conventional mapping of ventricular tachycardia (VT) after myocardial infarction is limited in patients with hemodynamically untolerated or noninducible VT. OBJECTIVES: The purpose of this study was to develop a unique strategy using noncontact unipolar mapping to define infarct substrate and VT circuits. METHODS: Dynamic substrate mapping (DSM) was performed in seven pigs with healed anterior myocardial infarction. This technique defined substrate as the intersection of low-voltage areas identified in sinus rhythm and during pacing around the infarct. Pacing was also performed within the substrate to determine exit sites. RESULTS: Anteroapical transmural scar was identified in all animals. A mean of three pacing sites was used for substrate definition. The mean area (+/- SD) was 18.4 +/- 8.8 cm2 by DSM and 15.4 +/- 6.9 cm2 by pathology (P >.5). A mean of 4.5 sites was paced within substrate. Ten of 18 paced wavefronts exited substrate adjacent to the pacing area, seven exited at distant areas, and one had two exits. VT was induced in five animals (1.6 morphologies per animal). Except for one VT, circuit exit sites were identified at substrate borders on the endocardium. VT exit sites were at (n = 6) or near (n = 3) a pacing exit site. Electrogram voltages differed significantly between substrate, border, and nonsubstrate areas in infarcted animals and in comparison with control animals. No substrate was identified in two control animals. CONCLUSION: DSM is a reliable method for infarct substrate localization in this model. Pacing within substrate can predict VT exit sites and may prove useful for ablation of unmappable VT after myocardial infarction.

Animals↗
PubMed2006

Delayed occurrence of unheralded phase IV complete heart block after ethanol septal ablation for symmetric hypertrophic obstructive cardiomyopathy.

Ethanol septal ablation has emerged as a less invasive alternative to surgical myomectomy for treatment of asymmetric hypertrophic obstructive cardiomyopathy (ASH). The procedure has very low mortality, but high-degree AV conduction block is a frequent complication. Prior studies have documented baseline left bundle branch block and high volume of ethanol injection (greater than 4 mL) as risk factors. Complete heart block is often preceded by postprocedure conduction abnormalities and generally develops within 48 hours after ethanol ablation. We present a unique case of a patient with symmetric hypertensive hypertrophic obstructive cardiomyopathy (SHOCM) who developed phase IV complete heart block >96 hours postprocedure without preceding conduction abnormalities or other classic risk factors.

Cardiomyopathy, Hypertrophic↗
PubMed2005

Potent block of inactivation-deficient Na+ channels by n-3 polyunsaturated fatty acids.

A voltage-gated, small, persistent Na(+) current (I(Na)) has been shown in mammalian cardiomyocytes. Hypoxia potentiates the persistent I(Na) that may cause arrhythmias. In the present study, we investigated the effects of n-3 polyunsaturated fatty acids (PUFAs) on I(Na) in HEK-293t cells transfected with an inactivation-deficient mutant (L409C/A410W) of the alpha-subunit (hH1(alpha)) of human cardiac Na(+) channels (hNav1.5) plus beta(1)-subunits. Extracellular application of 5 microM eicosapentaenoic acid (EPA; C20:5n-3) significantly inhibited I(Na). The late portion of I(Na) (I(Na late), measured near the end of each pulse) was almost completely suppressed. I(Na) returned to the pretreated level after washout of EPA. The inhibitory effect of EPA on I(Na) was concentration dependent, with IC(50) values of 4.0 +/- 0.4 microM for I(Na) peak (I(Na peak)) and 0.9 +/- 0.1 microM for I(Na late). EPA shifted the steady-state inactivation of I(Na peak) by -19 mV in the hyperpolarizing direction. EPA accelerated the process of resting inactivation of the mutant channel and delayed the recovery of the mutated Na(+) channel from resting inactivation. Other polyunsaturated fatty acids, docosahexaenoic acid, linolenic acid, arachidonic acid, and linoleic acid, all at 5 microM concentration, also significantly inhibited I(Na). In contrast, the monounsaturated fatty acid oleic acid or the saturated fatty acids stearic acid and palmitic acid at 5 microM concentration had no effect on I(Na). Our data demonstrate that the double mutations at the 409 and 410 sites in the D1-S6 region of hH1(alpha) induce inactivation-deficient I(Na) and that n-3 PUFAs inhibit mutant I(Na).

Cell Line↗
PubMed2005

Non-inducibility post-pulmonary vein isolation achieving exit block predicts freedom from atrial fibrillation.

AIMS: This study evaluates whether non-inducibility of atrial fibrillation (AF) after achieving bi-directional electrical pulmonary vein (PV) isolation is a useful predictor of freedom from AF recurrence. METHODS AND RESULTS: This study included 102 consecutive patients who underwent PV isolation for symptomatic paroxysmal (59%), persistent (32%), or permanent (9%) AF. Patients were followed for 16+/-10 months. Complete isolation of all four PVs was confirmed by demonstration of bi-directional block, defined by both loss of PV potentials and failure to capture the LA by pacing (at 10 mA) 10-14 bipolar pairs of electrodes on a circumferential catheter positioned at the entrance of the PV. Induction of AF by burst pacing on/off isoproterenol was attempted after PV isolation. Freedom from recurrent symptomatic or asymptomatic AF was present in 70% of patients at 6 months and 62% of patients at 12 months. In multi-variable analysis, non-inducibility post-PV isolation (OR=3.84, P=0.047) and paroxysmal AF (OR=4.80, P=0.012) predicted freedom from AF at 12 months. CONCLUSION: Non-inducibility of AF after bi-directional PV isolation predicts maintenance of sinus rhythm. This finding suggests that routine extensive left atrial ablation may be unnecessary.

Atrial Fibrillation↗
PubMed2005

QRS duration does not predict occurrence of ventricular tachyarrhythmias in patients with implanted cardioverter-defibrillators.

OBJECTIVES: The aim of this study was to determine whether QRS duration (QRSd) correlates with occurrence of ventricular arrhythmia in patients with coronary disease (CAD) receiving implantable cardioverter-defibrillators (ICDs). BACKGROUND: A QRSd measured on a standard electrocardiograph (ECG) correlates with total mortality risk in CAD patients at high risk for sudden death; however, the relationship between QRSd and risk of ventricular tachyarrhythmias (ventricular tachycardia/ventricular fibrillation [VT/VF]) is unclear. METHODS: PainFREE Rx II was a randomized trial, comparing efficacy of antitachycardia pacing versus shock therapy for VT/VF in patients receiving ICDs. We retrospectively correlated the QRSd and specific ECG conduction abnormalities on the 12-lead ECG at study entry with occurrence of VT/VF in 431 patients with CAD enrolled in the trial. RESULTS: The QRSd was < or =120 ms in 291 of 431 (68%) patients. Left bundle branch block (LBBB) was present in 65 patients, right bundle branch block (RBBB) in 48 patients, and nonspecific intraventricular conduction delay (IVCD) was present in 124 patients. Over 12 months' follow-up, VT/VF occurred in 95 (22%) patients (22% of patients with QRSd < or =120 ms vs. 23% of patients with QRSd >120 ms, p = NS). Patients with LBBB were less likely to experience at least one VT/VF episode than patients with QRSd <120 ms. Patients with RBBB and nonspecific IVCD did not differ from patients with narrow QRS complexes with regard to occurrence of tachycardias. CONCLUSIONS: The QRSd and ECG conduction abnormalities are not useful to predict ICD benefit in patients having the characteristics of our study population. The utility of QRSd to predict VT/VF events in patients with CAD requires further prospective evaluation.

Aged↗
PubMed2005

T-vector direction differentiates postpacing from ischemic T-wave inversion in precordial leads.

BACKGROUND: Postpacing precordial T-wave inversion (TWI), known as cardiac memory (CM), mimics ischemic precordial TWI, and there are no established ECG criteria that adequately distinguish between the two. On the basis of CM properties (postpacing sinus rhythm T vector approaching the direction of the paced QRS vector), we hypothesized that CM induced by right ventricular pacing would manifest a TWI pattern different from that of precordial ischemic TWI, thereby discriminating between the two. METHODS AND RESULTS: T-wave axis, polarity, and amplitude on a 12-lead ECG during sinus rhythm were compared between CM and ischemic patients. The CM group incorporated 13 patients who were paced in DDD mode with short atrioventricular delay for 1 week after elective pacemaker implantation. The ischemic group consisted of 47 patients with precordial TWI identified among 228 consecutive patients undergoing percutaneous coronary intervention for an acute coronary syndrome. The combination of (1) positive T(aVL), (2) positive or isoelectric T(I), and (3) maximal precordial TWI>TWI(III) was 92% sensitive and 100% specific for CM, discriminating it from ischemic precordial TWI. CONCLUSIONS: CM induced by right ventricular pacing results in a distinctive T-vector pattern that allows discrimination from ischemic precordial T-wave inversions regardless of the coronary artery involved.

Aged↗
PubMed2005

Cardiac memory: mechanisms and clinical implications.

Cardiac memory (CM) is identified as an altered T wave on electrocardiogram and vectorcardiogram that is seen when sinus rhythm resumes after a period of abnormal myocardial activation. Specifically, the sinus rhythm T wave tracks the QRS vector of the abnormal impulse. CM frequently is induced by ventricular pacing or arrhythmias and historically has been considered of minor relevance to medical practice. Although it has long been known that CM can mimic the T-wave inversions of myocardial ischemia, we learned more recently that CM can alter the actions of antiarrhythmic drugs. Furthermore, it provides a template for investigating the mechanisms whereby ventricular pacing affects myocardial physiology. In this article we review the mechanisms believed responsible for induction of CM and some of its more recently recognized clinical manifestations. We also discuss the controversies regarding atrial memory and its potential clinical implications.

Animals↗
PubMed2004

Is there a role for maintaining sinus rhythm in patients with atrial fibrillation?

Recent studies have indicated that outcomes in patients with atrial fibrillation who are managed with rate control and anticoagulation are similar to those in patients who have maintenance of sinus rhythm. These studies did not include important groups of patients with atrial fibrillation in whom antiarrhythmic therapy may be appropriate. This perspective argues for the maintenance of sinus rhythm and for the use of antiarrhythmic therapy that includes medications, invasive procedures, and a combination of both in appropriate patients.

Anti-Arrhythmia Agents↗