Comparison of dilated cardiomyopathy and coronary artery disease in patients with life-threatening ventricular arrhythmias: Differences in presentation and outcome in the AVID registry.

BACKGROUND: The etiology of structural heart disease in patients with life-threatening arrhythmias (ventricular tachycardia [VT]/ventricular fibrillation [VF]) may define clinical characteristics at presentation, may require that different therapies be administered, and may cause different mortality outcomes. METHODS: In the Antiarrhythmics Versus Implantable Defibrillators (AVID) registry, baseline clinical characteristics, treatments instituted, and ultimate mortality outcomes from the National Death Index were obtained on 3117 patients seen at participating institutions with VT/VF, irrespective of participation in the randomized trial. By use of these data, 2268 patients with coronary artery disease (CAD) were compared with 334 patients with dilated nonischemic cardiomyopathy (DCM). RESULTS: The CAD group was 7 years older and had a higher percentage of males. DCM patients were more likely to be African American, have severely compromised left ventricular function (52% vs 39%), and have a history of congestive heart failure symptoms (62% vs 44%). Patients with CAD were more likely to be treated with b-blockers and calcium channel blockers and less likely to be treated with angiotensin-converting enzyme inhibitors. Patients with DCM were more likely to be treated with diuretics, warfarin, and an implantable cardioverter defibrillator for VT/VF (54% vs 48% for CAD); the use of other antiarrhythmic therapies did not differ between the 2 groups. Two-year survival was not significantly different between the groups (76.6% [95% CI 74.6%-78.7%] vs 78.2% [95% CI 73.6%-82.9%]). CONCLUSIONS: In AVID registry patients with VT/VF, demographic and clinical characteristics were different between patients with CAD and those with DCM. Despite these differences, overall survival was similar in these 2 groups.

Resumption of driving after life-threatening ventricular tachyarrhythmia.

BACKGROUND: Although the privilege of driving must be respected, it may be necessary to restrict driving when it poses a threat to others. The risks associated with allowing patients with life-threatening ventricular tachyarrhythmias to drive have not been quantified. METHODS: The Antiarrhythmics versus Implantable Defibrillators (AVID) trial compared antiarrhythmic-drug therapy with the implantation of defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. In the current study, we sent patients who participated in the AVID trial a questionnaire, to be completed anonymously, requesting information about driving habits and experiences. RESULTS: The questionnaire was returned by 758 of 909 patients (83 percent). Of these, 627 patients drove during the year before their index episode of ventricular tachyarrhythmia. A total of 57 percent of these patients resumed driving within 3 months after randomization in the AVID trial, 78 percent within 6 months, and 88 percent within 12 months. While driving, 2 percent had a syncopal episode, 11 percent had dizziness or palpitations that necessitated stopping the vehicle, 22 percent had dizziness or palpitations that did not necessitate stopping the vehicle, and 8 percent of the 295 patients with an implantable cardioverter-defibrillator received a shock. Fifty patients reported having at least 1 accident, for a total of 55 accidents during 1619 patient-years of follow-up after the resumption of driving (3.4 percent per patient-year). Only 11 percent of these accidents were preceded by symptoms of possible arrhythmia (0.4 percent per patient-year). CONCLUSIONS: Most patients with ventricular tachyarrhythmias resume driving early. Although it is common for them to have symptoms of possible arrhythmia while driving, accidents are uncommon and occur with a frequency that is lower than the annual accident rate of 7.1 percent in the general driving population of the United States.

Validation of three myocardial jeopardy scores in a population-based cardiac catheterization cohort.

BACKGROUND: The Jeopardy Score from Duke University and the Myocardial Jeopardy Index from the Bypass Angioplasty Revascularization Investigation (BARI) have been validated but never applied to a large unselected cohort. We assessed the prognostic value of these existing jeopardy scores, along with that of a new Lesion Score developed for the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH), a clinical data collection initiative capturing all patients undergoing cardiac catheterization in the province of Alberta. METHODS: The predictive value of these three scores were compared in a cohort of >20,000 patients (9922 treated medically, 6334 treated with percutaneous intervention, and 3811 treated with bypass surgery). Scores were considered individually in logistic regression models for their ability to predict outcome and then added to models containing sociodemographic data, comorbidities, ejection fraction, indication for procedure, and descriptors of coronary anatomy. RESULTS: All scores were found to be predictive of 1-year mortality, especially when patients are treated medically or with percutaneous intervention. In these patients, the APPROACH Lesion Score performed slightly better than the other jeopardy scores. The Duke Jeopardy Score was most predictive in those patients undergoing coronary bypass surgery. CONCLUSIONS: Myocardial jeopardy scores provide independent prognostic information for patients with ischemic heart disease, especially if those patients are treated medically or with percutaneous intervention. These scores represent potentially valuable tools in cardiovascular outcome studies. The APPROACH Lesion Score may perform slightly better than previously developed jeopardy scores.

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.

Baseline factors predicting early resumption of driving after life-threatening arrhythmias in the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial.

BACKGROUND: In the Antiarrhythmics Versus Implantable Defibrillators (AVID) Trial, patients with ventricular fibrillation or hemodynamically unstable ventricular tachycardia were randomly assigned to receive either an implantable cardioverter-defibrillator (ICD) or antiarrhythmic drug therapy. As part of the trial, patients were asked to participate in a prospective driving survey. The purpose of the survey was to determine what baseline factors and patient characteristics specifically predicted resumption of driving earlier than advised by current guidelines. METHODS: Patients were surveyed anonymously as to their driving habits in the initial period after random assignment and every 6 months thereafter. AVID study coordinators were independently asked to assess their patients' driving status as well. The relation between baseline factors and time to resumption of driving was explored by means of Kaplan-Meier estimates for univariate analyses and the stepwise Cox proportional hazards regression model for multivariate analyses. RESULTS: There were 802 patients who were eligible for assessment of driving status. The majority of patients (58%) resumed driving an automobile within 6 months of their index arrhythmia regardless of whether they received drug therapy or an ICD. By multivariate analysis, patients who were younger than 65 years of age, male, and college educated were more likely to drive early, as were patients whose index arrhythmia was ventricular tachycardia. CONCLUSIONS: Younger, college-educated men and those whose index arrhythmia is ventricular tachycardia are most likely to resume driving <6 months after the initiation of therapy for a potentially life-threatening ventricular arrhythmia. Patients with an ICD did not appear to resume driving later than those who were discharged on antiarrhythmic drugs alone.

Long-term survival in 11,661 patients with multivessel coronary artery disease in the era of stenting: a report from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) Investigators.

BACKGROUND: Studies of survival of patients with multivessel coronary artery disease (MVD) in the prestent era suggested that outcomes after coronary artery bypass surgery (CABG) are similar to those after percutaneous coronary intervention (PCI) in subsets of coronary severity. The purpose of this study of the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) was to examine the association between treatment and survival up to 5 years in patients with MVD enrolled from 1995 through 1998. METHODS AND RESULTS: Data on patient characteristics were obtained at the time of the initial coronary angiography. Survival was determined through data linkage to the provincial Bureau of Vital Statistics. Risk-adjusted hazard ratios were calculated to compare different treatments. In the 11,661 patients with MVD, CABG was the initial therapy in 3782, PCI in 3540, and medical therapy in 4339. Cumulative 5-year survival was 91.4% with CABG, 91.9% with PCI, and 82.9% with medical therapy (P <.001). Hazard ratios were CABG: medical 0.53 (95% confidence interval [CI] 0.46-0.71), PCI: medical 0.65 (95% CI 0.56-0.74), and CABG: PCI 0.81 (95% CI 0.68-0.96). Analysis across coronary severity groups revealed a benefit of CABG compared with PCI only in the group with severe left main CAD: 0.30 (95% CI 0.17-0.54). CONCLUSIONS: In a multicenter clinical setting, MVD patients treated with revascularization have significantly higher 5-year survival rate than do those treated medically. Risk-adjusted comparison reveals PCI treatment to be associated with long-term survival similar to treatment with CABG in all coronary severity subgroups except the group with severe left main coronary artery disease. Patient selection factors are likely to be contributing to these findings.

Characterization of viable autofluorescent macrophages among cultured peripheral blood mononuclear cells.

BACKGROUND: Inflammatory macrophages that demonstrate intense autofluorescence have been isolated directly from alveolar and peritoneal tissues, but their generation in vitro remains vague. We use flow cytometry to identify a population of autofluorescent macrophages as they arise among nonadherent populations of cultured blood mononuclear cells. METHODS: Cells were obtained from donated blood buffy coats and placed in culture for 14 days. Unstained populations from the cells remaining in suspension were sampled daily using flow cytometry. During the first 5 culture days, a distinct population of autofluorescent cells arose and comprised an average of < or =14% of the total cell population. This population declined to less than 6% by culture day 8. RESULTS: The cells were identified as viable macrophages expressing CD68, lysozyme, and HLA-DR. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) demonstrated a unique cytokine profile with IL-1 alpha expression levels 138-fold higher than those measured in uncultured monocytes. No significant elevation in the levels of other cytokines was identified. Upon replating, the sorted populations became readherent, were able to ingest plastic beads, and remained viable for 6 or more additional weeks in culture without evidence of proliferation or multinucleation. CONCLUSION: Viable autofluorescent macrophage populations arising among cultured peripheral blood may be easily identified and isolated for further study using flow cytometry. Cytometry 44:38-44, 2001. Published 2001 Wiley-Liss, Inc.

Prognostic significance of diabetes as a predictor of survival after cardiac catheterization. APPROACH Investigators. Alberta Provincial Program for Outcome Assessment in Coronary Heart Disease.

PURPOSE: Diabetes is a recognized risk factor for the development of cardiac disease, but its importance as a prognostic factor among patients with known cardiovascular disease is less clear. We evaluated survival in patients with and without diabetes who underwent cardiac catheterization for presumed coronary artery disease. SUBJECTS AND METHODS: We analyzed data from a prospective cohort study that captures detailed clinical information and longitudinal outcomes for all patients who undergo cardiac catheterization in Alberta, Canada. We studied 11,468 patients, 1959 (17%) of whom had diabetes. Logistic regression was used to model predictors of 1-year mortality, and proportional hazards analysis was used to model predictors of survival up to 3 years after cardiac catheterization. RESULTS: One-year mortality was 7.6% for patients with diabetes versus 4.1% for those without diabetes (odds ratio = 1.9, 95% confidence interval [CI]: 1.6 to 2.3). After adjusting for other characteristics of the patients, including comorbid conditions, previous cardiac history, coronary anatomy, and renal function, the odds ratio for 1-year mortality was 1.1 (95% CI: 0.8 to 1.3). Similarly, the adjusted hazard ratio for longer term mortality was 1. 2 (95% CI: 1.0 to 1.4, mean follow-up of 702 days). CONCLUSIONS: These results suggest that there is little or no independent association between diabetes and mortality for up to 3 years after cardiac catheterization. Estimates of short- to intermediate-term prognosis for diabetic patients with coronary artery disease should be based on the presence of other prognostic factors associated with diabetes.

Simple modified ultrafiltration.

After reviewing all available methods of modified ultrafiltration (MUF), an attempt was made to develop a more simplified approach to this beneficial method of post-bypass fluid removal by withdrawing blood from the right atrium and reinfusing into the aortic cannula (venoarterial). The simplicity of operation, ease of setup and analysis of hemoglobin, hematocrit, total proteins and colloid osmotic pressure, and fluid removed were examined in 12 consecutive neonatal and pediatric patients undergoing cardiac surgery. Results indicate that this simplified modified ultrafiltration (SMUF) is comparable to all other methods of MUF by achieving dramatic improvements in all parameters measured. In addition, SMUF provides the perfusionist with the ability to run conventional ultrafiltration throughout the bypass procedure, using this one circuit design. As well as finding the learning curve for SMUF to be very short, this method was found to be superior in its simplicity of operation, ease of setup, reduced risk of complications and acceptance by the surgeon and anesthetist.

Drug therapy of sustained ventricular tachyarrhythmias. Is there still a role?

This article provides a review of the risks faced by patients with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) in the absence of a reversible or transient cause so that the goals of therapy can be clearly defined. The therapeutic approaches that have been proposed to achieve these goals are outlined and evidence comparing these various approaches to therapy is then summarized in order to propose an algorithm for the optimal use of antiarrhythmic drug therapies as primary therapy for selected VT/VF patients. Options for the ancillary uses of antiarrhythmic drug therapies in ICD patients are considered.

Canadian implantable defibrillator study (CIDS) : a randomized trial of the implantable cardioverter defibrillator against amiodarone.

BACKGROUND: Patients surviving ventricular fibrillation (VF) or sustained ventricular tachycardia (VT) are at a high risk of death due to a recurrence of arrhythmia. The implantable cardioverter defibrillator (ICD) terminates VT or VF, but it is not known whether this device prolongs life in these patients compared with medical therapy with amiodarone. METHODS AND RESULTS: A total of 659 patients with resuscitated VF or VT or with unmonitored syncope were randomly assigned to treatment with the ICD or with amiodarone. The primary outcome measure was all-cause mortality, and the secondary outcome was arrhythmic death. A total of 328 patients were randomized to receive an ICD. A thoracotomy was done in 33, no ICD was implanted in 18, and the rest had a nonthoracotomy ICD. All 331 patients randomized to amiodarone received it initially. At 5 years, 85.4% of patients assigned to amiodarone were still receiving it at a mean dose of 255 mg/day, 28.1% of ICD patients were also receiving amiodarone, and 21.4% of amiodarone patients had received an ICD. A nonsignificant reduction in the risk of death was observed with the ICD, from 10.2% per year to 8.3% per year (19.7% relative risk reduction; 95% confidence interval, -7.7% to 40%; P=0.142). A nonsignificant reduction in the risk of arrhythmic death was observed, from 4.5% per year to 3.0% per year (32.8% relative risk reduction; 95% confidence interval, -7.2% to 57.8%; P=0.094). CONCLUSIONS: A 20% relative risk reduction occurred in all-cause mortality and a 33% reduction occurred in arrhythmic mortality with ICD therapy compared with amiodarone; this reduction did not reach statistical significance.

Conduction time oscillations precede the spontaneous termination of human atrioventricular reciprocating tachycardia.

Prior clinical research indicates that conduction slowing is the primary mechanism leading to the spontaneous termination of reentrant tachycardia in humans. Yet, some experimental models indicate that cycle length oscillations and enhanced conduction are important prerequisites. The role of oscillations in conduction times and enhanced conduction in the spontaneous termination of human reentrant tachycardia has not been adequately investigated. The electrophysiologic features preceding the spontaneous termination of orthodromic atrioventricular (AV) reciprocating tachycardia (RT) were evaluated in 21 patients, each of whom had a sustained (>60 seconds) and a spontaneously terminating (>/=10 beats and

Telemetry-documented, pace-terminable ventricular tachycardia in patients with ventricular fibrillation.

The follow-up prevalence of electrogram-confirmed spontaneous ventricular tachycardia with a cycle length of >280 ms (53%) exceeds the prevalence of ventricular fibrillation (23%) in patients whose only spontaneous arrhythmia before implantable cardioverter defibrillator implantation was ventricular fibrillation. Antitachycardia pacing therapy safely terminates most (89%) of these slower ventricular tachycardia episodes, recommending the use of tiered-therapy devices and anticipatory activation of ventricular tachycardia detection and treatment algorithms for ventricular fibrillation patients who receive an implantable cardioverter defibrillator.

Antiarrhythmic drug effects on QT interval dispersion in patients undergoing electropharmacologic testing for ventricular tachycardia and fibrillation.

The effects of antiarrhythmic drugs on QT interval dispersion as a predictor of antiarrhythmic drug therapy has not been rigorously assessed. This study was performed to determine whether the effects of antiarrhythmic drugs on QT interval dispersion predict antiarrhythmic drug response in patients undergoing electropharmacologic testing for ventricular tachycardiarrythmias. Precordial QT intervals and QT interval dispersions were measured at baseline and during steady-state antiarrhythmic drug therapy in 72 consecutive patients with documented coronary artery disease and remote myocardial infarction presenting with spontaneous sustained ventricular tachyarrhythmias who underwent electropharmacologic studies to assess arrhythmia suppression. QT interval dispersion was similar at baseline in drug responders (42 +/- 21 ms) and drug nonresponders (46 +/- 21 ms), whereas during antiarrhythmic therapy QT interval dispersion was shorter in drug responders (33 +/- 15 ms) than in drug nonresponders (55 +/- 29 ms, p <0.001). QT interval dispersion was shorter in 7 drug responders during their effective drug trials (27 +/- 14 ms) than during their ineffective drug trials (47 +/- 24 ms, n = 9, p <0.05). QT dispersion < or = 50 ms (p <0.002) and a patent infarct-related artery (p <0.003) were independent predictors of antiarrhythmic therapy. The positive and negative predictive value of QT interval dispersion during drug therapy to predict a successful drug response was 32% and 96%, respectively. QT interval dispersion predicted the outcome of electropharmacologic studies independent of infarct-related artery patency. QT interval dispersion >50 ms during drug therapy was associated with ineffective drug therapy.

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.

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.