Correlation and stability of heart rate and ventricular ectopy variability in patients with congestive heart failure.

The stability of indexes of heart rate variability and their possible association with spontaneous variability of ventricular ectopy was examined in 13 patients with advanced congestive heart failure over 14 consecutive days of 24-hour ambulatory electrocardiographic recording. It was found that time and frequency domain measures of heart rate variability are stable over time and are inversely correlated with spontaneous variability of ventricular ectopy.

Relation of dispersion of QRS and QT in patients with advanced congestive heart failure to cardiac and sudden death mortality.

This study examined the usefulness of 01 and QRS dispersion in the prognosis of patients with advanced congestive heart failure (CHF). One hundred four patients in New York Heart Association functional classes II to IV, with a left ventricular ejection fraction of <35%, and untreated with antiarrhythmic drugs, were followed prospectively. QRS and QT dispersion were defined as the maximum difference in QRS and QT interval duration, respectively, measured on all leads of standard 12-lead electrocardiograms. The end points of the study were non-sudden and sudden cardiac mortality. During an average follow-up of 20 months, there were 13 non-sudden and 10 sudden deaths. The average QRS duration was significantly longer in nonsurvivors than in survivors (125 ¿ 34 vs 113 ¿ 34 ms, respectively, p <0.04). Similar results were obtained with 01 dispersion (95 ¿ 48 ms vs 78 ¿ 31 ms, respectively, p <0.03) and QRS dispersion (54 ¿ 17 ms vs 46 16 ms, respectively, p <0.02). Furthermore, patients who died suddenly had significantly greater QRS dispersion than patients who survived (56 ¿ 13 vs 46 ¿ 16 ms, respectively, p <0.02). In a multivariate analysis, QT and QRS dispersion were both independent predictors of non-sudden cardiac death (p = 0.01 and p = 0.001, respectively), and QRS dispersion was also an independent predictor of sudden cardiac death (p = 0.04). Death rate in patients with 01 dispersion >90 ms was 2.8-fold higher than those with 01 dispersion 90 ms (95% confidence intervals [CI] 1.2 to 6.4). Similarly, the death rate in patients with QRS dispersion >46 ms was 3.9-fold higher than in those with QRS dispersion 46 ms (95% Cl 1.6 to 9.5). These findings suggest that QT and QRS dispersion are useful predictors of mortality in patients with advanced CHF. ¿2000 by Excerpta Medica, Inc.

Heart rate changes preceding ventricular ectopy in patients with ventricular tachycardia caused by reentry, triggered activity, and automaticity.

OBJECTIVES: Although enhanced sympathetic tone is thought to be proarrhythmic and beta-blockade reduces the risk of sudden cardiac death in survivors of myocardial infarction, the role of the autonomic nervous system in triggering spontaneous ventricular ectopy and ventricular tachycardia (VT) has not been fully elucidated. The purpose of this study was to compare and contrast autonomic tone preceding spontaneous ventricular arrhythmias in patients with reentrant, triggered, and automatic forms of VT. BACKGROUND: The prevailing model of reentrant VT is based on a triggering beat interacting with a fixed substrate. Within this model, cyclic fluctuations in autonomic tone comprise a "third factor" that may initiate the triggering extrasystoles as well as alter the substrate, facilitating perpetuation of tachycardia. Consistent with this model, adrenergic stimulation can facilitate the induction of reentrant arrhythmias as well as arrhythmias resulting from enhanced automaticity and those caused by triggered activity resulting from cyclic adenosine monophosphate-dependent delayed afterdepolarizations. METHODS AND RESULTS: On the basis of the results at electrophysiologic study, 26 patients with coronary artery disease were identified as having reentrant VT, 11 were identified as having idiopathic VT caused by triggered activity, and 4 were identified as having idiopathic VT caused by enhanced automaticity. Each patient underwent 24-hour electrocardiographic monitoring, and the mean sinus R-R intervals immediately preceding each sinus beat as well as the 15 beats preceding sinus beats, premature ventricular contractions (VPCs), and complex ventricular ectopy (couplet/non-sustained VT) were computed. In addition, high-frequency heart rate variability was determined. Heart rate accelerated before spontaneous ventricular ectopy for all three arrhythmia mechanisms. R-R intervals preceding episodes of complex ventricular ectopy were significantly shorter than the corresponding intervals preceding single VPCs in patients with 'riggered VT [p=0.006 and 0.01, R-R(-1) and R-R(-15), respectively] and in those with reentrant VT (p=0.007 and p=0.05). There were no corresponding differences in high-frequency heart rate variability. R-R intervals preceding single VPCs were significantly shorter than the corresponding intervals preceding sinus beats in patients with automatic VT (p=0.0004 and 0.0001, respectively), which was accompanied by a small reduction in high-frequency heart rate variability (p=0.04). CONCLUSIONS: Heart rate accelerates before spontaneous ventricular ectopy in patients with VT. The acceleration is disproportionate to parasympathetic withdrawal, implicating increased endogenous sympathetic tone in the genesis of spontaneous ventricular arrhythmias caused by all three electrophysiologic mechanisms: reentry, triggered activity, and automaticity.

Prognostic significance of echocardiographically estimated right ventricular shortening in advanced heart failure.

Little is known about the association of echocardiographic estimates of right ventricular (RV) function with survival, in relation to hemodynamic and exercise-derived predictors of outcome in congestive heart failure. We prospectively studied 40 patients (age 55+/-10 years, in New York Heart Association functional class III [70%] and IV [30%]), with left ventricular (LV) ejection fraction <30%. At enrollment, all patients underwent echocardiographic evaluation of LV dimensions and function. RV shortening was measured as the difference of the end-diastolic distance - the end-systolic distance between the tricuspid annulus and the RV apex. Thirty-five patients (88%) were able to perform a maximal symptom-limited exercise test. Peak oxygen consumption (peak VO2) and percent peak age- and gender-adjusted predicted oxygen consumption (%peak VO2) were calculated. Of 40 patients, 10 died during a mean follow-up period of 14+/-10 months. On univariate analysis, nonsurvivors had lower RV shortening (p=0.0001), higher pulmonary artery wedge pressure (p=0.009), higher pulmonary vascular resistance (p=0.02), and lower mean aortic pressure (p=0.05). Cox proportional-hazards model revealed that the only independent associate of survival was RV shortening (p=0.0005), with a trend toward significance for mean aortic pressure (p=0.08). The best cutoff point of RV shortening identified by the receiver-operating curve was 1.25 cm. This value had a sensitivity of 90%, specificity of 80%, and overall predictive accuracy of 83% to distinguish survivors from nonsurvivors. In patients with advanced heart failure, preserved RV function as indicated by an echocardiographically derived RV shortening > 1.25 cm is a strong predictor of survival.

Multivariate associates of QT dispersion in patients with acute myocardial infarction: primacy of patency status of the infarct-related artery. TEAM-3 Investigators. Third trial of Thrombolysis with Eminase in Acute Myocardial Infarction.

BACKGROUND: QT dispersion (QTd; QT interval maximum minus minimum) has been shown to reflect regional variations in ventricular repolarization and is increased in patients with life-threatening ventricular arrhythmias. METHODS: To determine correlates of QTd in patients who had had myocardial infarction (MI), 207 patients (158 men, aged 57 +/- 11 years) with acute MI who were treated with alteplase or anistreplase within 2.7 +/- 0.9 hours of symptom onset were studied. Angiograms at a median of 27 hours after thrombolysis showed reperfusion (Thrombolysis in Myocardial Infarction grade > or =2) in 184 (88%) patients. QT was measured in 10 +/- 2 leads on discharge electrocardiograms with a computerized analysis program interfaced with a digitizer. Associations of QTd with 24 variables related to patient characteristics, acute MI, angiography, interventions, and radionuclide ventriculography were evaluated by univariate and multivariate regression. RESULTS: Univariate associations with QTd (p < or = 0.10) were Thrombolysis in Myocardial Infarction flow grade 0/1 versus 2/3 (QTd = 75 +/- 33 msec vs 53 +/- 22 msec, p < 0.0001), minimal luminal diameter (p = 0.007), left ventricular ejection fraction at discharge (p = 0.007), reinfarction (p = 0.01), number of leads with ST elevation (p = 0.05), end-systolic volume at discharge (p = 0.04), time to peak creatine kinase (p = 0.06), and YST elevation (p = 0.10). Independent associates of QTd were Thrombolysis in Myocardial Infarction grade 0/1 versus 2/3 (p < 0.0001), reinfarction (p = 0.005), and ejection fraction (p = 0.02). CONCLUSIONS: Successful thrombolysis is associated with less QTd in patients after acute MI. Our results support the hypothesis that QTd after MI depends on reperfusion status, reinfarction, and left ventricular function. Reduction in QTd may be an additional mechanism by which the benefit of thrombolytic therapy is realized.

"Rescue" utilization of abciximab for the dissolution of coronary thrombus developing as a complication of coronary angioplasty.

OBJECTIVES: This study sought to test the effect on thrombus score of the "rescue" utilization of the glycoprotein IIb/IIIa antagonist abciximab given to patients in whom intracoronary thrombus has developed as a complication after percutaneous transluminal coronary angioplasty (PTCA) and to determine its clinical utility. BACKGROUND: Abciximab is effective in the prevention of acute ischemic complications when given prophylactically to patients during high risk PTCA. However, its ability to therapeutically dissolve newly formed intracoronary thrombus occurring as a complication after PTCA is not known. METHODS: We performed an observational study in 29 consecutive patients who received abciximab (0.25 mg/kg body weight intravenous bolus, followed by a 12-h infusion at 10 microg/min) after attempted PTCA caused either the new development or further progression of thrombus. Angiograms were analyzed to determine thrombus score and Thrombolysis in Myocardial Infarction (TIMI) flow grade before and after abciximab. Procedural and clinical success and long-term outcome were also determined. RESULTS: Thrombus score decreased from 3.0 +/- 0.9 (mean +/- SD) to 0.86 +/- 0.92 (p < 0.001), and TIMI flow grade increased from 2.5 +/- 0.7 to 2.9 +/- 0.3 (p = 0.008). No instances of distal embolization or no-reflow were noted. The procedural success (< or = 50% residual stenosis) rate was 97%. The clinical success (procedural success with no in-hospital myocardial infarction, bypass surgery or death) rate was 93%. CONCLUSIONS: Dissolution of thrombus and restoration of TIMI grade 3 flow were readily achieved after administration of abciximab when delivered in a "rescue" manner after the development of thrombosis after PTCA. This novel use of abciximab will need to be validated in randomized trials.

Predictive value for future arrhythmic events of fractal dimension, a measure of time clustering of ventricular premature complexes, after myocardial infarction. CAST Investigators. Cardia Arrhythmia Suppression Trial.

OBJECTIVES: Our objective was to test fractal dimension (D), a measure of clustering of ventricular premature complexes (VPCs), on entry Holter recording as a predictor of future arrhythmic death and other-cause mortality in postinfarction patients in the Cardiac Arrhythmic Suppression Trial (CAST). BACKGROUND: Nonlinear dynamic methods of signal processing are being applied in medicine to provide new insights into apparently "chaotic" biologic events, including cardiac arrhythmias. One such application is the derivation of a fractal D to describe the clustering of VPCs in time. METHODS: Baseline Holter recordings were analyzed in blinded manner for 484 patients: 237 died or had a resuscitated cardiac arrest during follow-up, and 247 matched patients had no events. Fractal D, measured in four ways, was assessed as a predictor using Cox regression. RESULTS: One measure of D (high resolution D) was a significant univariate (relative hazard ratio 0.79 per SD change, p = 0.011) and multivariate (hazard ratio 0.75, p = 0.046) predictor of arrhythmic death but not other death (univariate p = 0.95, relative hazard 0.95, p = 0.66). Fractal D was greater (VPCs less clustered) in those patients free of arrhythmic events. On subgroup analysis, the predictive value of D resided in the randomized patient group (i.e., those who showed VPC suppression during initial antiarrhythmic drug titration and were randomized to blinded therapy with active drug or placebo) (multivariate hazard ratio 0.57, p = 0.001). CONCLUSIONS: A high resolution fractal D was predictive of arrhythmic (but not nonarrhythmic) death in a large postinfarction cohort. Further study of this new signal processing approach to ambulatory electrocardiographic recording will be of interest.

Reproducibility of drug efficacy predictions by Holter monitoring in the electrophysiologic study versus electrocardiographic monitoring (ESVEM) trial. ESVEM Investigators.

Selection of antiarrhythmic therapy may be based on suppression of spontaneous ventricular arrhythmias assessed by Holter monitoring, but the implications of discordant Holter results on repeat 24-hour monitoring has not been defined. This study examines the frequency and significance of reproducible Holter suppression on two 24-hour recordings in the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial. Repeat 24-hour Holter monitoring was obtained in patients randomized to the Holter monitor limb of the ESVEM trial, during the same hospitalization, after a drug efficacy prediction. These Holters were not used to define drug efficacy but were subsequently analyzed to determine the reproducibility of drug efficacy predictions by Holter monitoring. A repeat 24-hour Holter monitor, following the one that predicted drug efficacy, was available in 119 patients. Ninety-nine patients (83%) also had suppression that met efficacy criteria on the second Holter monitor. There were no significant differences in arrhythmia recurrence (p = 0.612) or mortality (p = 0.638) in patients with concordant Holter results (n = 99; 1-year arrhythmia recurrence = 45%; 1-year mortality = 10%) compared with those with discordant Holter results (n = 20; 1-year arrhythmia recurrence = 45%; 1-year mortality = 16%). We conclude that (1) there is discordance between the first effective Holter monitor and a repeat Holter monitor in 17% of patients, and (2) suppression of ventricular ectopic activity on 2 separate 24-hour Holter monitors does not identify a group with a better outcome, nor does failure of suppression on the second Holter monitor identify a group with a worse prognosis.

Impact of the Food and Drug Administration approval of flecainide and encainide on coronary artery disease mortality: putting "Deadly Medicine" to the test.

In his book Deadly Medicine and on television, Thomas Moore impugns the process of antiarrhythmic drug approval in the 1980s, alleging that the new generation of drugs had flooded the marketplace and had caused deaths in numbers comparable to lives lost during war. To assess these important public health allegations, we evaluated annual coronary artery disease death rates in relation to antiarrhythmic drug sales (2 independent marketing surveys). Predicted mortality rates were modeled using linear regression analysis for 1982 through 1991. Deviations from predicted linearity were sought in relation to rising and falling class IC and overall class I antiarrhythmic drug use. Flecainide came to market in 1986 and encainide in 1987. Combined class IC sales peaked in 1987 and 1988 (maximum market penetration, 20%, first quarter 1989). Results of the Cardiac Arrhythmia Suppression Trial (CAST) were disclosed in April 1989. Overall annual class I antiarrhythmic prescription sales actually fell slightly (-3% to -4%/yr) in the 2 years before CAST and then more abruptly (- 12%) in the year after CAST (1990). Sales of class IC drugs fell dramatically after CAST (by 75%). Coronary death rates (age adjusted) fell in a linear fashion during the decade of 1982 through 1991. No deviation from predicted rates was observed during the introduction, rise, and fall in class IC (and other class I) sales: rates were 126/100,000 in 1985 (before flecainide), 114 and 110 in 1987 and 1988 (maximum sales), and 103 in 1990 (after CAST). Deviations in death rates in the postulated range of 6,000 to 25,000 per year were shown to be excluded easily by the 95% confidence intervals about the predicted rates. Entry of new antiarrhythmic drugs in the 1980s did not lead to overall market expansion and had no adverse impact on coronary artery disease death rates, which fell progressively. Thus, the allegations in Deadly Medicine could not be confirmed.

Explaining discrepant mortality results between primary percutaneous transluminal coronary angioplasty and thrombolysis for acute myocardial infarction.

Differing relative outcomes in randomized versus registry studies comparing primary angioplasty with thrombolytic therapy for acute myocardial infarction suggest a clinical paradox. A predictive model based on differences in 5 treatment-related factors, including time to therapy, patency success, and angioplasty experience, suggests that relative outcomes may indeed vary, depending on the clinical setting in which therapy is given.

Metaanalysis of five reported studies on the relation of early coronary patency grades with mortality and outcomes after acute myocardial infarction.

Coronary patency has been used as a measure of thrombolysis success after acute myocardial infarction (AMI). The Thrombolysis in Myocardial Infarction (TIMI) study grading scale for coronary perfusion has gained wide acceptance, but the significance of individual grades on clinical outcome has not been adequately tested. We hypothesized that optimal outcomes would be achieved only with early (and maintained) TIMI grade 3 (complete) perfusion compared with TIMI grade 2 (partial perfusion, previously classified as a reperfusion success) or grades 0 or 1 (occluded arteries). Five recent, angiographically controlled, prospectively performed studies of thrombolysis in AMI were identified, representing 3,969 patients. Odds ratios for mortality by early perfusion grades were calculated using the Mantel-Haenszel test and combined in a weighted fashion. Results for selected clinical and laboratory outcomes by patency grade were also assessed. Overall, mortality averaged 8.8% for TIMI grade 0/1, 7.0% for grade 2, and 3.7% for grade 3 perfusion. The odds ratio (OR) for early mortality was substantially reduced for grade 3 versus <3 perfusion (OR = 0.45, confidence interval [CI] 0.34 to 0.61, p <0.0001). In pairwise comparisons, grade 3 was clearly superior to grade 2 (OR = 0.54, CI) 0.37 to 0.78, p = 0.001) as well as grades 0/1 (OR = 0.41, CI 0.30 to 0.56, p <0.0001). Acute and convalescent ejection fraction, regional wall motion, time to enzyme peaks (creatine kinase [CK], creatine kinase myocardial bond [CK-MB]), peak enzyme levels [CK, lactate dehydrogenase [LDH], LDH-1), and risk of heart failure were each significantly less in patients achieving grade 3 than grade 2 (or lower grades) perfusion. Results were observed despite the frequent use of interventions after angiography. This meta-analysis demonstrates that early and complete (grade 3) flow is associated with superior survival and clinical outcome; grade 2 perfusion results in an inferior outcome, closer to that of an occluded than an open artery. The goal of reperfusion strategies should be early and maintained TIMI grade 3 perfusion.

An emergency department-based protocol for rapidly ruling out myocardial ischemia reduces hospital time and expense: results of a randomized study (ROMIO).

OBJECTIVES: We tested the hypothesis that an emergency department-based protocol for rapidly ruling out myocardial ischemia would reduce hospital time and expense but maintain diagnostic accuracy. BACKGROUND: Patients with a missed diagnosis of myocardial infarction have a high mortality rate; however, providing routine hospital care to low risk patients may not be time- or cost-effective. METHODS: One hundred low risk patients were entered into the study and randomized either to an emergency department-based rapid rule-out protocol (n = 50) or to routine hospital care (n = 50). Patients receiving routine care were managed by their attending physicians. The rapid protocol included serum enzyme testing at 0, 3, 6 and 9h, serial electrocardiograms with continuous ST segment monitoring and, if results were negative, a predischarge graded exercise test. Study patients were also compared with 160 historical control subjects. RESULTS: Myocardial infarction or unstable angina occurred in 6% of patients within 30 days; no diagnoses were missed. By intention to treat analysis (n = 50 in each group), the hospital stay was shorter and charges were lower with the rapid protocol than with routine care (p = 0.001). Among patients in whom ischemia was ruled out, those assigned to the rapid protocol had a shorter hospital stay (median 11.9 vs. 22.8 h, p = 0.0001) and lower initial ($893 vs $1,349, p = 0.0001) and 30-day ($898 vs. $1,522, p = 0.0001) hospital charges than did patients given routine care. In historical control subjects, the hospital stay was longer (median 34.5 h, p = 0.001 vs. either group) and charges greater (median $2,063, p = 0.001, vs rapid protocol, p = 0.02, vs. routine care group). CONCLUSIONS: In low risk patients who present to the emergency department with chest pain, the rapid protocol ruled out myocardial infarction and unstable angina more quickly and cost-effectively than did routine hospital care.

Increased incidence of Chlamydia species within the coronary arteries of patients with symptomatic atherosclerotic versus other forms of cardiovascular disease.

OBJECTIVES: The objectives of this study were to test prospectively for an association between Chlamydia and atherosclerosis by comparing the incidence of the pathogen found within atherosclerotic plaques in patients undergoing directional coronary atherectomy with a variety of control specimens and comparing the clinical features between the groups. BACKGROUND: Previous work has suggested an association between Chlamydia pneumoniae infection and coronary atherosclerosis, based on the demonstration of increased serologic titers and the detection of bacteria within atherosclerotic tissue, but this association has not yet been regarded as established. METHODS: Coronary specimens from 90 symptomatic patients undergoing coronary atherectomy were tested for the presence of Chlamydia species using direct immunofluorescence. Control specimens from 24 subjects without atherosclerosis (12 normal coronary specimens and 12 coronary specimens from cardiac transplant recipients with subsequent transplant-induced coronary disease) were also examined. RESULTS: Coronary atherectomy specimens were definitely positive in 66 (73%) and equivocally positive in 5 (6%), resulting in 79% of specimens showing evidence for the presence of Chlamydia species within the atherosclerotic tissue. In contrast, only 1 (4%) of 24 nonatherosclerotic coronary specimens showed any evidence of Chlamydia. The statistical significance of this difference is a p value < 0.001. Transmission electron microscopy was used to confirm the presence of appropriate organisms in three of five positive specimens. No clinical factors except the presence of a primary nonrestenotic lesion (odds ratio 3.0, p = 0.057) predicted the presence of Chlamydia. CONCLUSIONS: This high incidence of Chlamydia only in coronary arteries diseased by atherosclerosis suggests an etiologic role for Chlamydia infection in the development of coronary atherosclerosis that should be further studied.

Incomplete recanalization as an important determinant of Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow after thrombolytic therapy for acute myocardial infarction. TEAM Investigators. Thrombolytic Trial of Eminase in Acute Myocardial Infarction.

The outcome of patients with Thrombolysis in Myocardial Infarction (TIMI) trial grade 2 flow is worse than that of patients with TIMI grade 3 flow after thrombolytic therapy for acute myocardial infarction. It is unclear whether TIMI grade 2 flow represents incomplete recanalization of the culprit lesion or poor distal runoff. The Thrombolytic Trial of Eminase (anistreplase) in Acute Myocardial Infarction (TEAM)-2 and TEAM-3 were randomized trials comparing anistreplase with streptokinase (TEAM-2, n = 370) or with alteplase (tissue plasminogen activator) (TEAM-3, n = 325). We compared the minimal luminal diameter of the culprit lesion in patients with TIMI grade 2 flow with that in patients with TIMI grade 3 flow both 90 minutes (TEAM-2) and 1 day (TEAM-3) after thrombolysis. Patients with TIMI grade 2 flow had a lower residual luminal diameter in the culprit lesion than patients with TIMI grade 3 flow (TEAM-2, 0.58 +/- 0.03 vs 0.79 +/- 0.02 mm, p = 0.0001; TEAM-3, 0.88 +/- 0.04 vs 1.17 +/- 0.03 mm, p = 0.0001, for patients with TIMI grades 2 and 3 flow). Residual percent stenosis was correspondingly higher in patients with TIMI grade 2 flow. At the early angiogram, 66% of patients with TIMI grade 2 flow, but only 35% of those with TIMI grade 3 flow, had a minimal luminal diameter of 0.6 mm (positive predictive value 87%, negative predictive value 35%). Incomplete recanalization of the culprit lesion may thus be an important determinant of TIMI grade 2 flow after thrombolysis. Whether more complete thrombolysis or rescue angioplasty improves outcome in these patients deserves evaluation.

Electrophysiologic effects of antiarrhythmic drug therapy in the prediction of successful suppression of induced ventricular tachycardia.

Predictors of a successful outcome of serial electrophysiologic (EP) and drug studies have been identified from among baseline patient characteristics but not from among measures of baseline and drug-related EP effects. Identifying such predictors would be useful in explaining the mechanism of successful drug therapy and in guiding drug development and selection. We prospectively studied EP characteristics in 159 trials in 62 patients with ventricular tachycardia or ventricular fibrillation during antiarrhythmic therapy and compared EP measures between successful (n = 30) and failed trials (n = 129). The average age of the patients was 64 years (range 27 to 78 years); 82% were men and 18% women; and 87% had coronary artery disease. Measurements included R-R, QRS, and QT intervals during intrinsic rhythm and during pacing at cycle lengths of 600 of 400 msec; ventricular effective refractory periods (ERP) during pacing at cycle lengths of 600 and 400 msec; and changes in these measures, comparing treatment with drug-free baseline. Univariate predictors of success (in order of significance) included ERP600/QRS600, sotalol versus other drugs, ERP400/QRS400, delta ERP600, delta R-R, ERP600, QRS400 (negative association), delta ERP400, QRS600 (negative association), ERP400 (all p < 0.1). In two separate multivariate models, one for each drive cycle length, only the ratio ERP600/QRS600 (p = 0.01) in the first model and ERP400/QRS400 (p = 0.01) in the second model were significantly and independently associated with achieving noninducibility with drug therapy. Therefore measures of greater refractoriness and lesser delays in conduction velocity (ie, greater "wavelength") relate to drug success.(ABSTRACT TRUNCATED AT 250 WORDS)

Fractal clustering of ventricular ectopy correlates with sympathetic tone preceding ectopic beats.

BACKGROUND: Fractal geometric analysis of ventricular ectopy yields a fractal dimension, which can range from zero to one and is inversely related to clustering of ventricular premature contractions (VPCs). Low values of this fractal dimension, which reflect significantly nonuniform distributions of ventricular ectopy, are found in patients with life-threatening ventricular arrhythmias and predict adverse outcomes in selected patients with congestive heart failure and with mitral regurgitation. However, the physiological mechanism and correlates of the fractal dimension are unknown. METHODS AND RESULTS: To explore the physiological correlates of clustered ventricular ectopy, we studied 30 patients with a history of sustained ventricular tachycardia or ventricular fibrillation who had inducible sustained monomorphic ventricular tachycardia during electrophysiological study and also underwent drug-free 24-hour ambulatory ECG. In addition to fractal dimension (determined by use of our previously described algorithm), we measured the mean RR interval (+/- SD) for all sinus beats preceding a sinus beat and for all sinus beats preceding a single VPC and the mean root-mean-square difference (RMSSD) of all windows of 15 successive RR intervals (excluding ectopic beats) preceding a sinus beat and preceding a single VPC. Based on the directional changes of mean RR (a measure of both sympathetic and parasympathetic tone) and of RMSSD (a measure of parasympathetic tone), each patient's inferred relative sympathetic tone preceding ventricular ectopy was classified as increased, unchanged, or decreased. If these values changed concordantly, relative sympathetic tone was indeterminate. Fractal dimension did not correlate with the mean RR interval, SD of the RR interval, or RMSSD preceding sinus beats or preceding VPCs (all P > .10). In 20 patients, fractal dimension was significantly lower among those with increased relative sympathetic tone (n = 14) than those with unchanged or decreased sympathetic tone (n = 6, P = .008). Ten patients had indeterminate relative sympathetic tone. CONCLUSIONS: Clustering of ventricular ectopy, as measured by the fractal dimension, is observed in patients at increased risk of sudden cardiac death. A low fractal dimension (clustered ventricular ectopy) is related to changes in heart rate and heart rate variability that are consistent with transient increases in cardiac sympathetic tone.

Comparison of signal-averaging electrocardiographic systems using device specific criteria in 104 normal subjects.

UNLABELLED: The advent of several signal-averaged electrocardiogram (SAECG) systems for late potential (LP) assessment warrants comparisons to assess intersystem reproducibility and variability. Simultaneous SAECGs on two systems, Arrhythmia Research Technology (ART) and Marquette (MEI), were performed on 104 normal volunteers (53 males, age 44 +/- 14 years), and analyzed filtered QRS duration (TFQRS), root mean square voltage (RMS40), and low amplitude signal duration (LAS40), filtered at 40-250 Hz. The Gomes criteria (TfQRS > 114 msec, RMS40 < 20 microV and LAS40 > 38 msec) were used as criteria for LP. The data was also analyzed using the recently proposed system specific criteria for MEI (TFQRS > 120 msec, RMS40 < 20 microV and LAS40 > 38 msec). Where appropriate, statistical analysis was performed using simple linear and Spearman's rank correlation, analysis of variance, Finn's R and McNemar's test. RESULTS: The means +/- SD for ART and MEI were: TFQRS: 97.2 +/- 8.9 vs 108.2 +/- 7.2 msec (R = 0.76), RMS40: 31.8 +/- 17.8 vs 45.3 +/- 19.9 microV (R = 0.53), and LAS40: 32.2 +/- 8.4 vs 30 +/- 7.4 (R = 0.54). When the Gomes criteria were applied, the number of subjects identified by each system as abnormal were: TFQRS = 3 vs 22 (P < 0.001), RMS40 = 20 vs 8 (P = 0.004), LAS40 = 21 vs 9 (P = 0.004), TFQRS/RMS40 = 3 vs 6 (P = 0.38), TFQRS/LAS40 = 3 vs 7 (P = 0.22), RMS40/LAS40 40 = 17 vs 8 (P = 0.02), and all three criteria = 3 vs 6 (P = 0.38) for ART vs MEI, respectively. Percent agreement was 81.7% for TFQRS and 84.6% for RMS40 and LAS40 when single criteria were applied. Agreement improved when combined criteria were utilized (87.5%-95.2% for any two criteria and 95.2% for all three criteria). The intersystem agreement that was not due to chance was 0.63-0.69 for single criteria and 0.75-0.90 for combined criteria. Disagreement was highly significant for the three criteria when used singly and for RMS40 and LAS40 combined. Disagreement was not significant when TFQRS was used in combination with > or = one other criteria. When the MEI criteria were applied, there was a decrease in the number of subjects identified by the MEI system as abnormal, using the TFQRS criteria singly or in combination. Percent agreement for system specific TFQRS measurements was 94.2% for single criteria and 97.1% for combined criteria. The intersystem agreement that was not due to chance improved (88-0.94). Disagreement between system specific criteria for TFQRS was not significant (P > 0.05). CONCLUSION: Our data indicate that although there is a general correlation between ART and MEI measurements, variability is substantial, leading to significant differences when the criteria for LP are applied, especially for single parameter determinations. Thus, there is a need to establish system specific normal ranges and more accurate criteria for LP parameters.

Reduction in QT interval dispersion by successful thrombolytic therapy in acute myocardial infarction. TEAM-2 Study Investigators.

BACKGROUND: QT dispersion (QTd, equals maximal minus minimal QT interval) on a standard ECG has been shown to reflect regional variations in ventricular repolarization and is significantly greater in patients with than in those without arrhythmic events. METHODS AND RESULTS: To assess the effect of thrombolytic therapy on QTd, we studied 244 patients (196 men; mean age, 57 +/- 10 years) with acute myocardial infarction (AMI) who were treated with streptokinase (n = 115) or anistreplase (n = 129) at an average of 2.6 hours after symptom onset. Angiograms at 2.4 +/- 1 hours after thrombolytic therapy showed reperfusion (TIMI grade > or = 2) in 75% of patients. QT was measured in 10 +/- 2 leads at 9 +/- 5 days after AMI by using a computerized analysis program interfaced with a digitizer. QTd, QRSd, JT (QT minus QRS), and JT dispersion (JTd, equals maximal minus minimal JT interval) were calculated with a computer. There were significant differences in QTd (96 +/- 31, 88 +/- 25, 60 +/- 22, and 52 +/- 19 milliseconds; P < or = .0001) and in JTd (97 +/- 32, 88 +/- 31, 63 +/- 23, and 58 +/- 21 milliseconds; P = .0001) but not in QRSd (25 +/- 10, 22 +/- 7, 28 +/- 9, and 24 +/- 9 milliseconds; P = .24) among perfusion grades 0, 1, 2, and 3, respectively. Similar results were obtained comparing TIMI grades 0/1 with 2/3 and 0/1/2 with 3. Patients with left anterior descending (versus right and left circumflex) coronary artery occlusion showed significantly greater QTd (70 +/- 29 versus 59 +/- 27 milliseconds, P = .003) and JTd (74 +/- 30 versus 63 +/- 27 milliseconds, P = .004). Similarly, patients with anterior (versus inferior/lateral) AMI showed significantly greater QTd (69 +/- 30 versus 59 +/- 27 milliseconds, P = .006) and JTd (73 +/- 30 versus 63 +/- 27 milliseconds, P = .007). Results did not change when Bazett's QTc or JTc was substituted for QT or JT or when ANOVA included adjustments for age, sex, drug assignment, infarct site, infarct vessel, and number of measurable leads. On ANCOVA, the relation of QTd or JTd and perfusion grade was not influenced by heart rate. CONCLUSIONS: Successful thrombolysis is associated with less QTd and JTd in post-AMI patients. The results are equally significant when either QT or JT is used for analysis. These data support the hypothesis that QTd after AMI depends on reperfusion status as well as infarct site and size. Reduction in QTd and its corresponding risk of ventricular arrhythmia may be mechanisms of benefit of thrombolytic therapy.