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Biomedical subjects

L B Mitchell

Publications and source records attributed to L B Mitchell.

At least 37 records · Page 2Linked to original sources
PubMed1997

Definition of predicted effective antiarrhythmic drug therapy for ventricular tachyarrhythmias by the electrophysiologic study approach: randomized comparison of patient response criteria.

OBJECTIVES: We sought to compare efficacies of therapy for ventricular tachyarrhythmias selected by programmed stimulation using two different patient response efficacy criteria: <5 versus <16 repetitive ventricular responses. BACKGROUND: Therapy selection for ventricular tachyarrhythmias by programmed stimulation requires definition of a patient response that predicts long-term efficacy. Such definitions have not been previously compared prospectively. METHODS: Patients with sustained ventricular tachyarrhythmias were randomized to therapy selection using either the <5 or <16 repetitive response criterion of predicted effective therapy. The primary end point was sudden death or recurrence of ventricular tachyarrhythmia requiring intervention. RESULTS: Predicted effective drug therapy was found for 23 (34%) of 68 patients randomized to the <5 criterion and 29 (36%) of 81 patients randomized to the <16 criterion (p = NS). Definition of therapy required 3.0 +/- 1.6 drug trials (mean +/- SD) in patients randomized to the <5 criterion and 2.9 +/- 1.8 trials in patients randomized to the <16 criterion (p = NS). Patients randomized to the <5 criterion had a lower 2-year probability of the primary end point (0.20 +/- 0.05) than did patients randomized to the <16 criterion (0.33 +/- 0.05, one-tailed p = 0.004). The advantage of the <5 criterion was also seen in subgroup analyses involving patients with and without an initial drug efficacy prediction. CONCLUSIONS: The programmed stimulation approach to the selection of antiarrhythmic therapy for ventricular tachyarrhythmias using a patient response criterion of <5 repetitive ventricular responses results in a lower probability of recurrence of ventricular tachyarrhythmia than does use of a <16 repetitive response criterion.

Actuarial Analysis↗
PubMed1997

Effect of coronary angioplasty on precordial QT dispersion.

Dispersion of the QT interval is a measure of inhomogeneity of ventricular repolarization. Because ischemia is associated with regional abnormalities of conduction and repolarization, we hypothesized that the surface electrocardiographic interval dispersion would increase in patients with symptomatic coronary artery disease in the absence of myocardial infarction and that successful revascularization would reduce QT interval dispersion. Thirty-seven consecutive patients with ischemia due to 1-vessel coronary artery disease without prior myocardial infarction who underwent percutaneous transluminal coronary angioplasty (PTCA) were evaluated. Standard 12-lead electrocardiograms were performed 24 hours before, 24 hours after, and late (>2 months) after PTCA. Precordial QT interval dispersions were determined from differences in the maximum and minimum corrected QT intervals. Mean QT interval dispersion before PTCA was 60 +/- 9 ms, immediately after PTCA 23 +/- 14 ms (p <0.001), and late after PTCA 29 +/- 18 ms (p <0.001 vs before PTCA). The shortest precordial QT interval increased immediately after PTCA (367 +/- 40 vs 391 +/- 39 ms; p <0.02) and then remained stable late after PTCA (376 +/- 36 ms, p = NS vs immediately after PTCA). Symptomatic recurrent ischemia in 8 patients with documented restenosis increased QT interval dispersion (56 +/- 15 ms [p <0.01] vs 25 +/- 14 ms immediately after PTCA), which decreased again after successful repeat PTCA (22 +/- 13 ms [p <0.01] vs before the second PTCA). QT interval dispersion decreases after successful coronary artery revascularization and increases with restenosis. Therefore, QT interval dispersion may be a marker of recurrent ischemia due to restenosis after PTCA.

Aged↗
PubMed1997

Divergence of endocardial QT interval components during programmed electrical stimulation including observations during induction of sustained ventricular tachyarrhythmias.

Measurements were made in 12 normal subjects and during induction of sustained ventricular tachyarrhythmias in 31 patients with remote myocardial infarction. QT interval measurements were made semiautomatically with computer assistance and the total QT interval was divided into early (QT1) and late (QT2) components. QT intervals and QT interval dispersion between two right ventricular endocardial sites were plotted against the degree of prematurity of the last extrastimulus (S2, S3, or S4). In the control group, total QT and QT1 intervals shortened with increasing prematurity of the last extrastimulus (p < 0.001). Slopes (positive) were steeper with faster pacing rates (600, 500, or 400 ms) and more extrastimuli (1 to 3). The relationship between QT2 intervals and prematurity of the last extrastimulus was flat, but the slope was slightly negative (p = 0.05 to < 0.001) and did not vary with changes in pacing cycle length or number of extrastimuli. QT interval dispersion in the control group was minor (95% CI 0-40 ms). During induction of sustained ventricular tachyarrhythmias, total QT and QT1 intervals were longer (y intercepts) than in the control group (p < 0.05 at 400-ms pacing cycle length) and their dispersion was increased (p < 0.05). Generally, QT2 intervals were shorter (p < 0.05 at 600-ms pacing cycle length) during induction of ventricular arrhythmias in comparison with the control group but dispersion was increased (p < 0.05 at 400-ms pacing cycle length). QT intervals and QT interval dispersion show an orderly and predictable relationship with prematurity of the last extrastimulus in normal subjects. These patterns differ during induction of sustained ventricular tachyarrhythmias. Such differences may be exploited to derive clinically predictive and useful measurements.

Aged↗
PubMed1997

Clinical trials of antiarrhythmic drugs in patients with sustained ventricular tachyarrhythmias.

Patients with sustained ventricular tachyarrhythmias in the absence of a reversible cause require long-term therapy. Six approaches may have value in this setting, including individualized drug therapy selected by the invasive approach, individualized drug therapy selected by the noninvasive approach, beta-blocking therapy, amiodarone, transcatheter or electrosurgical ablation, and the implantable cardioverter defibrillator. Data supporting the four pharmacologic approaches and data comparing these approaches to one another and to the implantable cardioverter defibrillator are reviewed. Support for primary therapy with a beta-blocker is the weakest. Nevertheless, a role for concomitant beta-blockade is established. Comparisons of the invasive and noninvasive approaches suggest that, in drug-naive patients, the invasive approach is effective but the noninvasive approach is not, whereas in drug-resistant patients, neither approach is adequate. Data suggesting that amiodarone is more effective than individualized drug therapy is not compelling but is widely accepted. Given these uncertainties, many authorities have embraced the implantable cardioverter defibrillator as the therapy of choice.

Adrenergic beta-Antagonists↗
PubMed1996

Increased precordial QTc dispersion predicts ventricular fibrillation during acute myocardial infarction.

Electrocardiograms of 19 consecutive patients with acute myocardial infarction complicated by early ventricular fibrillation were compared with those in 19 case-matched patients with acute myocardial infarction not complicated by ventricular fibrillation. The mean precordial QTc interval dispersion in patients with ventricular fibrillation was greater than that of patients without ventricular fibrillation (73 +/- 28 ms vs 30 +/- 12 ms, p < 0.001).

Electrocardiography↗
PubMed1996

Use of the newer antiarrhythmic drugs in patients with supraventricular tachyarrhythmias: let's not throw out the baby with the bath water.

Although recent advances have expanded the therapeutic choices for patients with supraventricular tachyarrhythmias, most of these patients will still require either short or long term treatment with antiarrhythmic drugs. Unfortunately, some practitioners have reacted to recent reports emphasizing the hazards of antiarrhythmic drug therapies by adopting an attitude of avoidance of these therapies. Although critical analyses of available data indicate that many antiarrhythmic drugs may have an unfavourable risk-benefit balance in patients with low risk arrhythmias who also have atherosclerotic heart disease and/or congestive heart failure, the same cannot be said for patients with high risk arrhythmias, for patients without atherosclerotic heart disease or congestive heart failure, or for patients whose symptoms require antiarrhythmic therapy to prevent physical and emotional disability despite a small risk of therapy. These patients are not benefits by the prevalent nihilistic attitude of antiarrhythmic drug avoidance. The purpose of this review is to provide an electrophysiologic background for the rational selection of antiarrhythmic drug therapy for patients with supraventricular tachyarrhythmias with an accent of the newer agents that have been demonstrated to be useful for this purpose.

Anti-Arrhythmia Agents↗
PubMed1995

Spatial features in body-surface potential maps can identify patients with a history of sustained ventricular tachycardia.

BACKGROUND: Regional disparities of ventricular primary-repolarization properties contribute to an electrophysiological substrate for arrhythmias. Such disparities can be assessed from body-surface distributions of ECG QRST areas. Our objective was to isolate and test those features of QRST-area distributions that would be suitable for identifying patients at risk for life-threatening ventricular arrhythmias. METHODS AND RESULTS: We recorded ECGs simultaneously from 120 leads during sinus rhythm for 204 patients taking no antiarrhythmic drugs: half had had sustained ventricular tachycardia (VT); the other half, a myocardial infarction but no history of VT. For each patient, we calculated the QRST area in each lead and, using Karhunen-Loeve (K-L) expansion, reduced these data to 16 coefficients (each relating to one spatial feature, an eigenvector, derived from the total set of 204 QRST-area maps). Using stepwise discriminant analysis, we selected feature subsets that best discriminated between the two groups, and we estimated by a bootstrap procedure using 1000 trials how these subsets would perform on a prospective patient population. The mean diagnostic performance of the classifier for 1000 randomly selected training sets (n = 102 in each, with both groups equally represented) increased monotonically with the number of features used for classification. The initial trend for the corresponding test sets (n = 102 in each) was the same but reversed when the number of features exceeded eight. For an optimal set of eight spatial features, the sensitivity and specificity of the classifier for detecting patients with VT in 1000 test sets were (mean +/- SD) 90.3 +/- 4.3% and 78.0 +/- 6.1%, and its positive and negative predictive accuracies were 80.7 +/- 4.2% and 89.2 +/- 4.2%, respectively. Use of QRS duration as a supplementary feature to eight K-L coefficients can, in the test sets, increase specificity to 80.9 +/- 5.4% and positive predictive accuracy to 82.8 +/- 3.9% compared with the results for the optimal number of eight K-L features alone. CONCLUSIONS: Multiple body-surface ECGs contain valuable spatial features that can identify the presence of an arrhythmogenic substrate in the myocardium of patients at risk for ventricular arrhythmias. Our results compare very favorably with those achieved by any other known test, invasive or noninvasive, for arrhythmogenicity.

Body Surface Potential Mapping↗
PubMed1995

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.

Aged↗
PubMed1995

Definition of the best prediction criteria of the time domain signal-averaged electrocardiogram for serious arrhythmic events in the postinfarction period. The Cardiac Arrhythmia Suppression Trial/Signal-Averaged Electrocardiogram (CAST/SAECG) Substudy Investigators.

OBJECTIVES: The goal of this study was to establish guidelines for the prognostic use of the time domain signal-averaged electrocardiogram (ECG) after myocardial infarction. BACKGROUND: Previous studies of the prognostic use of the signal-averaged ECG in postinfarction patients had one or more of the following limitations: a small study group, empiric definition of an abnormal recording and possible bias in the selection of high risk groups or classification of arrhythmic events, or both. To correct for these limitations, a substudy was conducted in conjunction with the Cardiac Arrhythmia Suppression Trial (CAST). METHODS: Ten centers recruited 1,211 patients with acute myocardial infarction without application of the ejection fraction or Holter criteria restrictions of the main CAST protocol. Several clinical variables, ventricular arrhythmias on the Holter recording, ejection fraction and six signal-averaged ECG variables were analyzed. Patients with bundle branch block were excluded from the analysis, and the remaining 1,158 were followed for up to 1 year after infarction. The classification of arrhythmic events was reviewed independently by the CAST Events Committee. RESULTS: During an average (+/- SD) follow-up of 10.3 +/- 3.2 months, 45 patients had a serious arrhythmic event (nonfatal ventricular tachycardia or sudden cardiac arrhythmic death). A Cox regression analysis with only the six signal-averaged ECG variables indicated that the filtered QRS duration at 40 Hz > or = 120 ms (QRSD-40 Hz) at a cutpoint > or = 120 ms was the most predictive criterion of arrhythmic events. In a regression analysis that included all clinical, Holter and ejection fraction variables, a QRSD-40 Hz > or = 120 ms was the most significant predictor (p < 0.0001). The positive, negative and total predictive accuracy and odds ratio for QRSD-40 Hz > or = 120 ms were 17%, 98%, 88% and 8.4, respectively, and improved to 32%, 97%, 94% and 16.7, respectively, after combination with ejection fraction < or = 40% and complex ventricular arrhythmias on the Holter recording. CONCLUSIONS: The signal-averaged ECG predicts serious arrhythmic events in the first year after infarction better than do clinical, ejection fraction and ventricular arrhythmia variables, and QRSD-40 Hz > or = 120 ms provides the best predictive criterion in this clinical setting.

Arrhythmias, Cardiac↗
PubMed1995

Quinidine pharmacodynamics in patients with arrhythmia: effects of left ventricular function.

OBJECTIVES: This study was undertaken to determine whether quinidine pharmacodynamics are altered in the presence of left ventricular dysfunction. BACKGROUND: Left ventricular function is an independent predictor of antiarrhythmic drug efficacy. However, the effects of left ventricular dysfunction on the pharmacodynamics of antiarrhythmic drugs have not been studied extensively. METHODS: Signal-averaged electrocardiograms were obtained and quinidine plasma concentrations measured during 24-h quinidine washout in 22 patients. RESULTS: Linear quinidine concentration-effect relations were observed for QRS and QT intervals corrected for heart rate. The slopes of the concentration-effect relation describing changes in the corrected QT (QTc) interval were significantly higher in the group with left ventricular ejection fraction > or = 0.35 ([mean +/- SD] 29.5 +/- 11.2 ms/micrograms per ml) than in the group with a low left ventricular ejection fraction (15.7 +/- 9.7 ms/micrograms per ml, p = 0.001). The QRS concentration-effect relations were not different in the two groups. A significant linear correlation was observed between the slopes of the concentration-effect relations describing changes in QTc intervals and left ventricular ejection fraction (r = 0.7, p < 0.001). Nineteen patients with inducible ventricular tachycardia underwent serial electrophysiologic studies for evaluation of quinidine efficacy. Ventricular tachycardia could not be induced during quinidine therapy in eight patients. The slopes of the quinidine concentration-effect relations for QTc intervals were significantly higher in quinidine responders than in nonresponders (p < 0.05). CONCLUSIONS: The effects of quinidine on ventricular repolarization are linearly related to left ventricular ejection fraction. Quinidine concentration-effect relations describing ventricular repolarization are associated with antiarrhythmic efficacy in patients with ventricular tachycardia.

Cardiac Pacing, Artificial↗
PubMed1994

Prognostic significance of signal-averaged electrocardiogram after thrombolytic therapy and/or angioplasty during acute myocardial infarction (CAST substudy). Cardiac Arrhythmia Suppression Trial (CAST) SAECG Substudy Investigators.

Thrombolytic therapy and angioplasty during the early phase of an acute myocardial infarction (AMI) have been shown to improve prognosis. Time-domain analysis of the signal-averaged electrocardiogram (SAECG) provides strong, independent prediction of arrhythmic events (arrhythmic death/resuscitated cardiac arrest) after AMI. To determine whether the prognostic significance of an abnormal SAECG (QRS duration > or = 120 ms) measured after AMI is influenced by thrombolytic therapy/angioplasty given in the AMI period, the predictive value of SAECG was compared in patients with and without prior thrombolysis/angioplasty in a substudy of the Cardiac Arrhythmia Suppression Trial. Information was available in 787 patients. The average follow-up was 10 +/- 3 months and arrhythmic events occurred in 33 patients (4.2%). The prevalence of abnormal SAECG in patients with and without thrombolytic therapy/angioplasty was 9.4% (34 of 363 patients) and 14.9% (63 of 424 patients), respectively (p < 0.02). The arrhythmic event rate for patients with abnormal SAECG with and without thrombolytic therapy/angioplasty was 20.6% (7 of 34 patients) and 20.6% (13 of 63 patients), respectively. The arrhythmic event rate for patients with normal SAECG with and without thrombolytic therapy/angioplasty was 0.9% (3 of 329 patients) and 2.8% (10 of 361 patients), respectively. It is concluded that in patients with an AMI (1) the use of thrombolytic therapy/angioplasty is associated with a significantly decreased prevalence of abnormal SAECG, (2) thrombolytic therapy/angioplasty associated with a normal SAECG portends an excellent prognosis, and (3) an abnormal SAECG is predictive of an increased incidence of arrhythmic events in all patients regardless of prior thrombolytic therapy/angioplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Circadian pattern of arrhythmic death in patients receiving encainide, flecainide or moricizine in the Cardiac Arrhythmia Suppression Trial (CAST).

OBJECTIVES: The purpose of this study was to assess the effect of antiarrhythmic drugs on the timing of arrhythmic death. BACKGROUND: Sudden cardiac death remains a problem of epidemic proportions. Delineating its pathophysiology is an important step in devising preventive measures. Previous studies have shown a circadian pattern of onset of sudden cardiac death. The effect of antiarrhythmic drugs on this pattern has not been systematically studied. METHODS: The Cardiac Arrhythmia Suppression Trial (CAST) was a multicenter double-blind, placebo-controlled study designed to determine whether suppression of ventricular ectopic activity by means of antiarrhythmic drugs (encainide, flecainide or moricizine) after acute myocardial infarction would reduce the incidence of arrhythmic death. RESULTS: The trial was terminated prematurely because of an unexpectedly high mortality rate in the active treatment group. The onset of arrhythmic death in this group (in patients not receiving beta-adrenergic blocking agents) displayed a bimodal variation, with significant peaks in midmorning and late afternoon/early evening. More than half of the symptomatic events were accompanied by anginalike symptoms. Approximately 30% of all events occurred within 2 h of awakening. CONCLUSIONS: Our data suggest the possibility of a complex interaction among antiarrhythmic drugs, sympathetic nervous system activation and acute myocardial ischemia. Planning of future antiarrhythmic drug trials will need to take this information into account.

Aged↗
PubMed1994

New insights into the definition and meaning of proarrhythmia during initiation of antiarrhythmic drug therapy from the Cardiac Arrhythmia Suppression Trial and its pilot study. The CAST and CAPS Investigators.

OBJECTIVES: This study was undertaken to determine the characteristics of worsening ventricular arrhythmia during antiarrhythmic drug titration. BACKGROUND: Proarrhythmia is an evolving concept in cardiology. Its definition, incidence and clinical significance in various patient settings require refinement. METHODS: The impact of early proarrhythmia was analyzed in 3,840 patients in the Cardiac Arrhythmia Suppression Trial (CAST). RESULTS: Drug therapy did not affect the incidence of new, sustained but nonfatal ventricular tachycardia (placebo 0.5%, active drug 0.4%). Nevertheless, there was a threefold increase in arrhythmic death (placebo 0.5% vs. active drug 1.6%). The incidence of increased ventricular premature depolarizations was equivalent (3% to 5%) for the three study drugs and indistinguishable from that seen with placebo. Patients with increased ventricular premature depolarizations on the first drug tested had fewer at baseline (65 +/- 94 vs. 137 +/- 260 per hour; mean +/- SD) (p < 0.01). When increased ventricular premature depolarizations occurred with the first drug, they were much more likely also to be present with the second drug (for example, 42% vs. 5%, p < 0.001). Increased ventricular premature depolarizations during initiation of therapy independently predicted increased risk of subsequent arrhythmic death (independent relative risk 2.34, p = 0.0053) in the absence of continued antiarrhythmic drug therapy. CONCLUSIONS: The overall incidence of early worsening of arrhythmia in the present study was low. In the absence of placebo control, the incidence of proarrhythmia will be overestimated. Increased ventricular premature depolarizations had characteristics that suggest they often represent spontaneous variability rather than proarrhythmia. The main finding is that markedly increased ventricular premature depolarizations during drug titration predict long-term increased risk of arrhythmic death in this patient population despite absence of long-term antiarrhythmic drug therapy.

Aged↗
PubMed1994

Amiloride-quinidine interaction: adverse outcomes.

OBJECTIVES: Previous studies have reported beneficial antiarrhythmic effects when selected drugs were combined. The purpose of this study was to assess whether a favorable interaction would occur with amiloride and quinidine. DESIGN: The antiarrhythmic and electrophysiologic effects of quinidine alone and in combination with amiloride were assessed in 10 patients with inducible sustained ventricular tachycardia. Parallel electrophysiologic studies assessed this drug combination in guinea pig papillary muscle. RESULTS: None of the patients had adverse effects during quinidine monotherapy. However, seven of 10 patients had adverse responses to the combination treatment: three patients had suppression of inducible ventricular tachycardia during quinidine monotherapy but had sustained ventricular tachycardia induced during combination treatment; three other patients had somatic side effects that resulted in discontinuation of the combination therapy but were absent during quinidine monotherapy; and one patient had 12 episodes of sustained ventricular tachycardia during this combination therapy. The patient had no such response during monotherapy. Surface QRS duration was significantly more prolonged during combination therapy than during monotherapy. Parallel electrophysiologic effects assessed this drug combination in guinea pig papillary muscle. The combination of amiloride (1 mumol/L) and quinidine (10 mumol/L) synergistically decreased the maximum rate of rise of phase 0 of the action potential (Vmax) (43 +/- 12 V/sec) compared with quinidine alone (24 +/- 9 V/sec) because of a greater degree of tonic block of Vmax (14% +/- 6%) as compared to quinidine alone (3% +/- 3%) with no significant change in action potential duration. CONCLUSIONS: Amiloride exaggerates the effects of quinidine on QRS duration in patients and on Vmax during in vitro study, which implies that the proarrhythmic effect of the combination of amiloride and quinidine may be associated with synergistic increase in sodium channel blockade.

Action Potentials↗