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Biomedical subjects

Mark E Josephson

Publications and source records attributed to Mark E Josephson.

44 records · Page 3Linked to original sources

Use of electrogram characteristics during sinus rhythm to delineate the endocardial scar in a porcine model of healed myocardial infarction.

INTRODUCTION: Substrate-based catheter ablation of postmyocardial infarction (post-MI) ventricular tachycardia necessitates electroanatomic definition of the scarred endocardium. We sought to determine whether electrogram criteria during sinus rhythm could identify the location and extent of the myocardial scar by electroanatomic mapping. METHODS AND RESULTS: A porcine model of healed MI was generated by injecting agarose microspheres into the mid left anterior descending coronary artery. At least 4 weeks post-MI, the animals (n = 24) underwent detailed left ventricular endocardial electroanatomic mapping using a 4-mm-tip catheter (BioSense-Webster, Inc.). Based upon mapping data in normal animals, infarcted tissue was defined as bipolar electrogram amplitude < 1.5 mV and electrogram duration > or = 50 msec. Radiofrequency ablation lesions (2-10 per animal) were placed to tag the endocardial borders of the electroanatomic mapping-defined scar. The area of the scar defined by abnormal voltage amplitude was 25.9 +/- 15.4 cm2 (range 6.9-60.5). This area correlated well with that defined as scar by the electrogram duration criteria (26.4 +/- 16 cm2). Of those points remote from the infarct with falsely low voltage amplitude resulting from presumed poor catheter-tissue contact, 94% were correctly identified as normal when using the electrogram duration criteria. Late potentials were observed predominantly along the borders of the infarcted myocardium. The radiofrequency lesions placed to tag the scar borders were located along the scar periphery during gross pathologic examination. CONCLUSION: During normal sinus rhythm, both bipolar electrogram voltage amplitude and electrogram duration criteria are able to help differentiate normal from scarred myocardial tissue. Using these criteria, a detailed reconstruction of the endocardial scar can be rendered by electroanatomic mapping of the heart.

Animals↗

Relation of ejection fraction and inducible ventricular tachycardia to mode of death in patients with coronary artery disease: an analysis of patients enrolled in the multicenter unsustained tachycardia trial.

BACKGROUND: Fifty percent of deaths in patients with coronary disease occur suddenly. Although many factors correlate with increased mortality, there is little information regarding the influence of these factors on mode of death. As such, optimum methods to determine patients most likely to benefit from implantable defibrillator therapy are unclear. METHODS AND RESULTS: We analyzed the relation of ejection fraction and inducible ventricular tachyarrhythmias to mode of death in all 1791 patients enrolled in the Multicenter Unsustained Tachycardia Trial who did not receive antiarrhythmic therapy. Total mortality and arrhythmic deaths/cardiac arrests occurred more frequently in patients with ejection fraction <30% than in those with ejection fraction of 30% to 40%. The percentage of deaths classified as arrhythmic was similar in patients with ejection fraction <30% or > or =30%. The relative contribution of arrhythmic events to total mortality was significantly higher in patients with inducible tachyarrhythmia (58% of deaths in inducible patients versus 46% in noninducible patients, P=0.004). The higher percentage of events that were arrhythmic among patients with inducible tachyarrhythmia appeared more distinct among patients with an ejection fraction > or =30% (61% of events were arrhythmic among inducible patients with ejection fraction > or =30% and only 42% among noninducible patients, P=0.002). CONCLUSIONS: Both low ejection fraction and inducible tachyarrhythmias identify patients with coronary disease at increased mortality risk. Ejection fraction does not discriminate between modes of death, whereas inducible tachyarrhythmia identifies patients for whom death, if it occurs, is significantly more likely to be arrhythmic, especially if ejection fraction is > or =30%.

Canada↗

Variable electrocardiographic characteristics of isthmus-dependent atrial flutter.

OBJECTIVES: The purpose of this study was to characterize variations in flutter-wave (F-wave) morphology among patients with clockwise isthmus-dependent (CWID) and counterclockwise isthmus-dependent (CCWID) right atrial flutter (AFL) and to attempt to correlate F-wave morphology with echocardiographic data and clinical patient characteristics. BACKGROUND: Variations in F-wave morphology on surface electrocardiogram (ECG) during CCWID and CWID flutter have been reported but never systematically characterized. METHODS: Over a four-year period, 139 patients with AFL on ECG underwent electrophysiologic study and echocardiography at our institution. Electrocardiographic data, intracardiac recordings, echocardiographic data, and patient characteristics were reviewed retrospectively. RESULTS: Of 156 AFLs evaluated, 130 were CCWID, 26 were CWID. Three types of CCWID flutter were observed: type 1 had purely negative F-waves inferiorly, types 2 and 3 had F-waves inferiorly with small (type 2) or broad (type 3) positive terminal deflections; CCWID flutter types 2 and 3 were associated with higher incidence of left atrial (LA) enlargement, heart disease, and atrial fibrillation (Afib) than type 1. Two types of CWID flutter were observed: type 1 had notched positive F-waves with a distinct isoelectric segment inferiorly. Type 2 had broader F-waves inferiorly with positive and negative components and a short isoelectric segment. CONCLUSIONS: Variable ECG patterns for CCWID and CWID AFL exist. A positive component of the F-wave in the inferior leads during CCWID flutter is associated with an increased likelihood of heart disease, Afib, and LA enlargement.

Adult↗

Effects of ventricular premature stimulus coupling interval on blood pressure and heart rate turbulence.

BACKGROUND: Heart rate turbulence (HRT) is a promising noninvasive risk stratifier for mortality after myocardial infarction. On the basis of a study of ventricular premature complex coupling interval and sympathetic nerve burst amplitude, we hypothesized that measures of HRT would increase with increased prematurity of the coupling interval. METHODS AND RESULTS: Twenty-eight patients undergoing programmed electrical stimulation were studied (12 with prior myocardial infarction, aged 60+/-18 years). An extrastimulus was delivered from the right ventricular apex after 20 sinus beats with a V-S(2) coupling interval decremented by 20 to 30 ms until refractoriness was reached. Turbulence slope (TS), turbulence timing (TT), and turbulence onset were calculated for each extrastimulus, and the linear regressions of these parameters on coupling interval and compensatory pause were calculated. Arterial blood pressure was measured with arterial catheter or a noninvasive continuous blood pressure transducer (Buffington cuff). TS and turbulence onset were abnormal in 4 and 13 patients, respectively. HRT parameters were significantly correlated with coupling interval or compensatory pause in only 2 or 3 patients for a given regression analysis. This absence of correlation was found likely to be due to lack of correlation between compensatory pause and systolic blood pressure after the compensatory pause. Heart rate and TS were correlated: Patients with high heart rate had low TS and late TT (TS=-2.7+0.01xsinus cycle length, P=0.018; TT=8.8 to 0.005xsinus cycle length, P=0.013). CONCLUSIONS: HRT can be induced by programmed stimulation. In this setting, heart rate affects HRT but not ventricular premature complex prematurity. Induced HRT seems to be a valid method for measuring HRT parameters in patients with few ventricular premature complexes.

Arrhythmias, Cardiac↗

Effect of implantable defibrillators on arrhythmic events and mortality in the multicenter unsustained tachycardia trial.

BACKGROUND: The Multicenter Unsustained Tachycardia Trial (MUSTT) was designed to evaluate an antiarrhythmic treatment strategy, including drugs and implantable defibrillators (ICDs), guided by electrophysiological (EP) testing. We performed several statistical analyses to assess the contribution of defibrillators to the observed treatment benefit. METHODS AND RESULTS: First, the effects of defibrillators were indirectly examined by comparing the randomized treatment arms (EP-guided therapy versus no antiarrhythmic therapy) within subgroups that varied according to ICD usage. Use of ICDs increased during the trial; hence, the randomized treatments were compared according to date of enrollment. There were also site-specific differences in ICD use; hence, the randomized arms were compared within groups of sites defined by level of ICD use. There was a distinct "dose response" in relation to ICD use. Where ICD use was high, EP-guided therapy produced significant reductions in arrhythmic death or cardiac arrest (P<0.004). Where ICD use was low, there was no benefit of EP-guided therapy. Finally, outcomes of EP-guided therapy patients who received an ICD were directly compared with outcomes of other patients using the Cox proportional hazards model with receipt of an ICD as a time-dependent covariate. Adjusted for other prognostic factors, patients who received an ICD had risk reductions of >70% in arrhythmic death or cardiac arrest and >50% in total mortality (P<0.001 for both end points). CONCLUSIONS: The benefit of EP-guided antiarrhythmic therapy observed in MUSTT was due to improved outcomes among patients who received an ICD but not among patients who received antiarrhythmic drugs.

Anti-Arrhythmia Agents↗

Typical AVNRT--an update on mechanisms and therapy.

Typical atrioventricular reentrant tachycardia (AVNRT) is the most common paroxysmal supraventricular tachycardia among adults, and accounts for considerable morbidity. The concept of dual pathway physiology remains useful, although this physiology likely results from the functional properties of anisotropic tissue within the triangle of Koch, rather than anatomically distinct tracts of conduction. Also, there remains debate regarding whether the critical reentrant circuit path requires participation of the atrium. In our opinion, current evidence favors functional anisotropic reentry limited to the subatrial tissues as the arrhythmia mechanism. Reasons for this are reviewed. Fortunately, typical AVNRT is readily amenable to definitive therapy by catheter-based radiofrequency energy delivery at the so-called slow pathway region located at the posterior Triangle of Koch. Anterior or left-sided approaches are very rarely indicated. Results from multiple series have shown this strategy to be both safe and effective, therefore ablation therapy should now be considered as the definitive therapy of choice for the majority of patients.

Atrioventricular Node↗

Prognostic significance of nonsustained ventricular tachycardia identified postoperatively after coronary artery bypass surgery in patients with left ventricular dysfunction.

INTRODUCTION: Nonsustained ventricular tachycardia (NSVT) occurs frequently in the postoperative period (< or = 30 days) after coronary artery bypass graft (CABG) surgery, a setting where many factors may play a role in its genesis. The prognosis of NSVT in this setting in patients with left ventricular (LV) dysfunction is unknown. This study was designed to assess its significance. METHODS AND RESULTS: We compared the outcome of untreated patients enrolled in the Multicenter Unsustained Tachycardia Trial with coronary artery disease (CAD), LV dysfunction, and NSVT identified postoperatively after CABG (n = 228; mean age 67 years, 84% males) versus nonpostoperative settings (n = 1,302; mean age 66 years, 85% males). Sustained monomorphic ventricular tachycardia was induced in 27% and 33% (P = 0.046) of patients with postoperative and nonpostoperative NSVT, respectively. The 2- and 5-year rates of arrhythmic events were 6% and 16%, respectively, in postoperative patients versus 15% and 29% in nonpostoperative patients (unadjusted P = 0.0020, adjusted P = 0.0082). The 2- and 5-year overall mortality rates were 15% and 36%, respectively, for postoperative patients versus 24% and 47% for nonpostoperative patients (unadjusted P = 0.0005, adjusted P = 0.027). Patients whose NSVT was identified early (<10 days) versus late (10-30 days) after CABG had significantly lower 2- (13% vs 23%) and 5-year (30% vs 52%) mortality rates (unadjusted P = 0.024, adjusted P = 0.018). CONCLUSION: In this population of patients with CAD and LV dysfunction, the occurrence of postoperative NSVT, especially within 10 days after CABG, portends a far better outcome than when it occurs in nonpostoperative settings. This suggests that in a such setting, NSVT represents a less specific risk factor for future events and should be considered when assigning risk and treatment of similar patients.

Adrenergic beta-Antagonists↗