Reproducibility and relative validity of a questionnaire to assess intake of black tea polyphenols in epidemiological studies.

Epidemiological studies suggest that tea drinking may reduce the risk of cardiovascular diseases and cancers. Although tea is an important source of antioxidant phytochemicals, variation in preparation techniques may translate to variation in antioxidant capacity. However, most large-scale epidemiological studies use regular food frequency questionnaires to estimate tea intake, and nationally available nutrient analysis databases do not include levels of black tea polyphenols. The Arizona Tea Questionnaire (ATQ) was designed as a tool for collecting more complete dietary tea consumption information, and a database was developed after analyzing 40 black tea samples (brewed, instant, and sun tea) for polyphenols. This study assesses the reliability and relative validity of the ATQ and polyphenol database. Relative validity of estimates of black tea consumption was tested by comparing the ATQ with the traditional Arizona Food Frequency Questionnaire and four days of food records. The ATQ was tested for reproducibility of estimates of black (hot and iced) tea consumption and levels of black tea polyphenol intake. Correlations between two measures of intake taken 2 months apart ranged from 0.72 for black hot tea to 0.86 for black sun tea. Mean intakes (range) of total flavonoids for black tea consumers were 80.8 (3.0-588.0) mg/day at the first ATQ and 102.4 (4.5-802.3) mg/day at the second ATQ (r = 0.83, P < 0.001). The ATQ provided highly reproducible estimates of both total tea consumption and individual tea polyphenol intake. This instrument may be a useful tool in studies of the associations between tea consumption, tea polyphenols intake, and risk for chronic disease.

Location of death (in-hospital or out-of-hospital) and type of death (arrhythmic, nonarrhythmic, noncardiac) after inducible sustained ventricular tachyarrhythmias after syncope, sustained ventricular tachycardia, or nonfatal cardiac arrest (the ESVEM trial).

The ESVEM Trial evaluated methods to guide antiarrhythmic drug use in patients with spontaneous, inducible sustained tachyarrhythmias at electrophysiologic testing and frequent ventricular premature complexes (VPCs) per hour (>/=10). We assessed the relation between location (in-hospital or out-of-hospital) and classification of death (arrhythmic, nonarrhythmic, cardiac and/or noncardiac) for 486 randomized patients. Deaths were classified as out-of-hospital arrhythmic deaths if arrhythmic death occurred out-of-hospital, or if an arrhythmia preceded hospital admission and directly caused death. Of the 486 randomized patients, 188 (39%) died during 6 years of follow-up. The location and type of death could be determined clearly in 171 patients (91%). Ninety-one deaths were in-hospital (53%); 80 were out-of-hospital (47%). Arrhythmic deaths occurred in 85% out-of-hospital patients and in 30% in-hospital patients (p <0.001). Baseline characteristics were comparable for patients with out-of-hospital and in-hospital arrhythmic deaths. Twenty-seven of 95 arrhythmic deaths occurred in-hospital (28%); 72% occurred out-of-hospital. Out-of-hospital arrhythmic death accounted for 40% of deaths for which location and type of information were available. The 1- and 4-year actuarial out-of-hospital arrhythmic death rates were 9% and 18%, respectively. Of nonarrhythmic cardiac deaths, 91% were in-hospital and 9% were out-of-hospital. Of noncardiac deaths, 74% were in-hospital and 26% were out-of-hospital. Similar results were seen in the 296 patients for whom a drug was considered to be effective. Thus, over half the deaths in the ESVEM trial occurred in-hospital. The long-term actuarial risk of out-of-hospital arrhythmic death in ESVEM was unexpectedly low.

Effect of ambulatory 24-hour esophageal pH monitoring on reflux-provoking activities.

Ambulatory 24-hr esophageal pH monitoring is considered the gold standard for diagnosing gastroesophageal reflux disease (GERD). The current approach is to encourage patients to pursue their everyday activity in order to obtain near-physiological recordings. However, the effect of the test itself on reflux-provoking activities has never been evaluated. Thus, the aim of our study was to assess daily food consumption, habits, symptoms, sleep, and perceived experience of patients undergoing pH testing as compared to an off test (normal) day. Patients reported type and time spent in each activity pursued, food ingested and length of each meal, habits, frequency and severity of GERD and other related symptoms, sleep disturbances, side effects, and overall perceived experience during pH testing and four weeks later, during a normal day. Fifty-four patients enrolled. pH testing significantly reduced time spent being active, number of meals and cups of coffee consumed, and frequency of GERD symptoms. Almost half of the patients reported having dysphagia during the test. Most patients experienced side effects and stated that the test bothered them most of the time. In conclusion, pH testing has a significant effect on decreasing reflux-provoking activities-patients tend to assume a more sedentary lifestyle. This may influence the reliability of the test as a physiologic measure of acid reflux.

Ventricular remodeling in active myocarditis. Myocarditis Treatment Trial.

BACKGROUND: Remodeling of the left ventricle with the development of a spherical cavity occurs in dilated cardiomyopathy and is associated with a poor long-term prognosis. The early effects of myocarditis on left ventricular geometry have not been previously described or correlated with clinical outcome. METHODS: The baseline echocardiograms of 35 patients with biopsy-confirmed myocarditis were compared with 20 normal controls. Left ventricular end-diastolic volume, long axis length, and mid-cavity diameter were measured. The degree of sphericity was expressed as the ratio of the mid-cavity diameter to the long axis length. Left ventricular ejection fraction was assessed by radionuclide angiography. RESULTS: In patients with myocarditis, mean left ventricular volume of 81 +/- 29 mL/m(2) was significantly greater than 50 +/- 8 mL/m(2) in controls (P =.001). Chamber dilatation occurred primarily along the mid-cavity diameter, which measured 5.3 +/- 0.8 cm in patients with myocarditis versus 4.2 +/- 0.4 cm in controls (P =.001). The degree of left ventricular sphericity in patients with myocarditis, 0.64 +/- 0.08, was significantly greater than that of controls, 0.54 +/- 0.04 (P =.001). When patients were stratified according to left ventricular volume, patients with increased left ventricular volume (>75 mL/m(2)) were associated with a more spherical chamber and lower left ventricular ejection fraction than patients with a more normal left ventricular volume (

Clinical significance of syncope in the electrophysiologic study versus electrocardiographic monitoring (ESVEM) trial. The ESVEM Investigators.

BACKGROUND: Syncope may portend risk of death, but which patients with syncope are at high risk remains unclear. OBJECTIVE: The ESVEM trial, a multicenter randomized prospective trial, provided the opportunity to compare mortality rates of patients enrolled with syncope to those enrolled with spontaneous ventricular arrhythmias. METHODS: Patients enrolled in the ESVEM trial presenting with syncope alone (25 patients) or in combination with ventricular tachycardia (24 patients) were compared with patients with spontaneous ventricular tachycardia alone (332 patients) or ventricular fibrillation (105 patients). All patients had ventricular tachyarrhythmias induced at electrophysiology testing of >/=10 premature ventricular complexes per hour on Holter monitor. RESULTS: Of all patients randomly assigned, arrhythmic death and total mortality rates were the same for those with syncope alone, with ventricular tachycardia and syncope, with ventricular tachycardia alone, or with ventricular fibrillation. At 1 year, arrhythmic and total mortality rate for all patients was 21% and 24%, respectively; for patients with syncope alone, 30% and 29%, respectively (P = NS). At 4 years, arrhythmic death and total mortality rate for all patients was 33% and 42%, respectively; for patients with syncope alone, 37% and 42%, respectively (P = NS). CONCLUSION: Syncope, associated with induced ventricular tachyarrhythmias at electrophysiologic testing, indicates high risk for death, similar to that of patients with documented spontaneous ventricular tachyarrhythmias.

Risk Factors for Tachycardia Events Caused by Antiarrhythmic Drugs: Experience From the ESVEM Trial.

BACKGROUND: In the Electrophysiology Study versus Electrocardiographic Monitoring (ESVEM) trial, up to seven antiarrhythmic drugs were randomly assigned to 486 patients with a history of sustained ventricular arrhythmia. At baseline, all the patients had inducible sustained ventricular tachycardia (VT) and had >/=10 premature ventricular beats (PVBs) per hour on 48-hour Holter monitoring. A total of 1,229 drug trials were performed. Antiarrhythmic drugs were discontinued during hospitalization because of ventricular tachyarrhythmias thought to be a proarrhythmic effect of the antiarrhythmic drugs in 96 of 479 patients (20%) who received drugs. Proarrhythmic effects were defined as sustained VT, ventricular fibrillation or arrhythmic death, torsade de pointes, or distinct intolerable worsening of the baseline arrhythmia after at least three doses of the drug. METHODS AND RESULTS: Eighteen baseline characteristics were analyzed for factors that would predict a higher incidence of proarrhythmia. These included type of heart disease, previous myocardial infarction, symptom activity scale, gender, type of arrhythmia, VT/ventricular fibrillation, age, left ventricular ejection fraction (LVEF), PVB frequency, heart rate, QRS duration, and QT interval. Multiple logistic regression analysis identified increased mean PVB frequency (P =.003) and increased heart rate (P =.026) as significant predictors of proarrhythmia. Decreased LVEF (<25%) exhibited only a trend toward significance (P =.073). When proarrhythmia was redefined as sustained VT, cardiac arrest of arrhythmic death, or torsade de pointes (n = 59), PVB frequency (P =.003) and heart rate (P =.034) were still the only significant baseline predictors. CONCLUSIONS: In the ESVEM study, higher PVB frequency and higher heart rate were significant predictors of drug-induced proarrhythmia.

Effect of reproducibility of baseline arrhythmia induction on drug efficacy predictions and outcome in the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial.

Spontaneous variability over time in the ease of induction of ventricular arrhythmias may mimic a drug effect and affect the predictive value of drug therapy guided by programmed stimulation. We assessed the effect of baseline reproducibility of arrhythmia induction on the incidence and accuracy of drug efficacy predictions in the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial. Patients with sustained ventricular tachyarrhythmias induced twice during baseline electrophysiologic testing with the same stimulation technique, i.e., induced at the same pacing site with the same drive cycle length and number of extrastimuli, were identified from the ESVEM database. These patients with highly reproducible arrhythmia induction were compared to those with less reproducible arrhythmias. Of 473 randomized patients with reproducibility data, 313 (66%) had highly reproducible arrhythmias. In patients randomized to electrophysiologic testing, baseline arrhythmia reproducibility did not affect the incidence of drug efficacy predictions (70 of 157 [45%], drug efficacy predictions in patients with highly reproducible arrhythmias vs 34 of 79 [43%] with less reproducible arrhythmias, p = 0.890). Drug efficacy predictions obtained by electrophysiologic testing in patients with highly reproducible arrhythmias were not associated with decreases in arrhythmia recurrence (p = 0.202), all-cause mortality (p = 0.301), cardiac death (p = 0.358), or arrhythmic death (p = 0.307) compared to those with less reproducible arrhythmias. Analysis of patients with highly reproducible sustained monomorphic ventricular tachycardia led to similar results. In the ESVEM trial, most patients had highly reproducible arrhythmia induction during baseline electrophysiologic testing. Reproducibility of arrhythmia induction in the baseline state had no effect on the incidence or accuracy of drug efficacy predictions.

Predictors of arrhythmic death and cardiac arrest in the ESVEM trial. Electrophysiologic Study Versus Electromagnetic Monitoring.

BACKGROUND: The purpose of this study was to determine if the presenting ventricular arrhythmia (ventricular tachycardia or ventricular fibrillation/cardiac arrest) predicted the type of arrhythmia recurrence in patients treated with antiarrhythmic drugs. METHODS AND RESULTS: In the previously reported Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial, there were 486 patients who were randomized to antiarrhythmic drug testing guided by electrophysiological study or by ambulatory ECG monitoring. Use of a defibrillator (implantable cardioverter-defibrillator, ICD) without stored electrograms among 81 patients precluded determination of the type of arrhythmia recurrence; thus these patients were censored at the time of ICD implantation. Of the 486 patients, 381 presented with ventricular tachycardia and 105 with cardiac arrest. Over a 6-year follow-up period, 285 of the 486 patients had an arrhythmia recurrence; of these, 97 had an arrhythmic death or cardiac arrest as a first recurrence. In the current analysis, all 129 arrhythmic deaths/cardiac arrests that occurred any time during follow-up were evaluated as end points. CONCLUSIONS: Although univariate analysis suggested that there was an association between the presenting arrhythmia and outcome, multivariate analysis failed to substantiate the predictive value of the presenting arrhythmia. Left ventricular ejection fraction was the single most important predictor of arrhythmic death or cardiac arrest. This information may be an important factor in deciding whether to advise ICD therapy.

Sotalol for ventricular tachyarrhythmias: beta-blocking and class III contributions, and relative efficacy versus class I drugs after prior drug failure. ESVEM Investigators. Electrophysiologic Study Versus Electrocardiographic Monitoring.

In the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial, d,l-sotalol was associated with a lower arrhythmia recurrence and mortality than class I antiarrhythmic drugs. To further evaluate the relative efficacy of d,I-sotalol compared with class I drugs, and to assess the relative importance of its class II (beta-blocking) and class III effects, 6-year arrhythmia recurrence and mortality in patients receiving sotalol were compared with those in patients receiving class I drugs, subdivided according to whether they also received coadministered beta blockers. Relative efficacy was also determined for sotalol and for class I drugs as stratified by the presence/absence of prior drug failure. Arrhythmia recurrence was lower for the 84 patients receiving sotalol than for patients given class I agents with (n = 28) (p = 0.008) or without (n = 184) (p = 0.001) alpha beta blocker. Mortality was lower for patients taking sotalol than for those given a class I drug without alpha beta blocker (p = 0.034), but similar (p = 0.835) if alpha beta blocker was also administered. In contrast to class I drugs, which had lower efficacy rates when prior drug trials had failed, sotalol maintained its efficacy despite prior drug failures preceding or during the ESVEM trial. Both class II and III actions in the ESVEM trial were important to the clinical superiority of sotalol in the treatment of ventricular tachyarrhythmias.

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.

Long-term cost-effectiveness of alternative management strategies for patients with life-threatening ventricular arrhythmias. Electrophysiologic Study versus Electrocardiographic Monitoring (ESVEM) Investigators.

BACKGROUND: Serial antiarrhythmic drug testing guided by Holter monitoring and electrophysiologic study had similar clinical outcomes in the Electrophysiologic Study versus Electrocardiographic Monitoring (ESVEM) trial, while patients treated with sotalol had improved outcomes. The purpose of this study was to compare long-term cost-effectiveness of these management alternatives. METHODS: Patients in the ESVEM trial were linked to computerized files of either the Health Care Finance Administration or the Department of Veterans Affairs. Total hospital costs and survival time over five year follow-up were measured using actuarial methods, and cost-effectiveness was calculated. RESULTS: Patients randomized to therapy guided by electrophysiologic study had more hospital admissions, higher costs, and a cost-effectiveness ratio of $162,500 per life year added compared with therapy guided by Holter monitoring. Patients randomized to sotalol had fewer hospitalizations, lower costs, and better survival than patients randomized to other drugs, and sotalol was a dominant strategy in the cost-effectiveness analysis. Patients for whom an effective drug was found had fewer hospital admissions, lower costs, and longer survival. These findings were robust in sensitivity analyses and in bootstrap replications. CONCLUSIONS: Serial drug testing guided by electrophysiologic study had an unfavorable cost-effectiveness ratio relative to Holter monitoring, while sotalol was cost-effective relative to other antiarrhythmic drugs.

Design and analysis of the ESVEM Trial.

Inadequate understanding of the design and statistical approach of a clinical trial and the failure to recognize subjective aspects of the analysis often result in misinterpretation of trial results. This is exacerbated by the push to shorten publications and the wish for a simple message that summarizes the outcome of the trial. The purpose of this review is to critically review the design and statistical analyses of the results, to evaluate the assumptions underlying the statistical tests, and to examine the results of exploratory analysis on the interpretation of major findings of the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial. The trial was unusual because its primary objective was to compare testing methods instead of treatments. This necessitated using a subset of the original randomized groups for sensible analysis of the clinical question. Nevertheless, the two groups appeared to be well balanced. The absence of a difference in outcome could be verified by several analyses. In addition, confidence intervals were narrow, indicating the high precision and reliability of the findings. However, the comparison of antiarrhythmic drugs is problematic because the trial was not designed to address this issue. There were differences in the distribution of clinical characteristics between the groups who received different antiarrhythmic drugs. Nevertheless, using both univariate analyses and a variety of adjustments for important prognostic variables, treatment with sotalol appeared to be a significant predictor of reduced arrhythmia recurrence, and sotalol was consistently associated with a trend for nearly a 50% reduction in sudden death and all-cause mortality as compared with the other drugs administered in the trial. In conclusion, the ESVEM trial raises a number of interesting and instructive issues about clinical trial design and analysis.

Influence of Holter monitor and electrophysiologic study methods and efficacy criteria on the outcome of patients with ventricular tachycardia and ventricular fibrillation in the ESVEM trial.

Because not all laboratories use the monitoring and stimulation protocols used in the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial, we reanalyzed the ESVEM patients' data using alternative, commonly used Holter monitor (HM) and programmed stimulation efficacy criteria to determine if different criteria would have changed the trial's conclusions. Also, because beta-blocker use and coronary artery disease frequency were not equally distributed between the two limbs in ESVEM, we reanalyzed the ESVEM data adjusting for the possible effect of these variables. In the HM limb, drug efficacy in the original ESVEM analysis was declared by reduction of total premature ventricular complexes (PVCs) by 70%, pairs by 80%, runs of 3 to 15 beats by 90%, and all ventricular tachycardia (VT) more than 15 beats by 100%. In this analysis, we examine outcome in subjects meeting two more stringent sets of criteria, (1) reduction of total PVCs by 70%, of pairs by 80%, and of all VT by 100% (new criteria set 1) and (2) reduction of total PVCs by 80%, of pairs by 90%, and of all VT by 100% (new criteria set 2). In electrophysiology (EPS) limb patients, we compared arrhythmia recurrence when efficacy was declared with triple extrastimuli as compared with maximally testing with double extrastimuli, and arrhythmia recurrence was compared in patients tested with identical versus any more aggressive protocol on drug than was used before drug. We also compared the predictive accuracy of zero versus 3 to 15, and 0 to 5, 6 to 10, and more than 10 induced beats on drug. Additionally, we compared predictive accuracy of the HM- and EP-guided limbs excluding patients on beta blockers and those with noncoronary disease. Lastly, to determine whether concordant results on HM and EPS testing would provide more accurate efficacy predictions than EP testing alone, HM recordings obtained in EPS-limb patients but not processed or used during the course of the EVSEM study were analyzed. The original ESVEM HM criteria, new set 1, and new set 2 yielded predicted drug efficacy rates of 77%, 68%, and 58%, respectively; however, arrhythmia recurrence rates were unchanged. Similarly, arrhythmia recurrence rates for patients tested with triple versus less than triple extrastimuli (p=.238), more aggressive versus identical protocols (p=.955), and 0 to 5 v 6 to 10 v more than 10 induced beats (p=.263) or 0 v 3 to 15 induced beats (p=.106) were unchanged. in the 215 (of 286) patients with coronary disease and not receiving beta blockers, there was still no difference in arrhythmia recurrence or mortality between the noninvasive and invasive limbs in ESVEM. Lastly, in patients with drug efficacy predictions by EPS testing, there was no difference in outcome in patients who had concordant versus discordant efficacy prediction by simultaneously obtained HMs. The use of more stringent testing methods and efficacy criteria would not have significantly improved the predictive accuracy of drug assessment by HM or EPS in the ESVEM trial. Additionally, excess noncoronary disease in EP-guided patients and excess beta-blocker used in HM-guided patients did not influence the results in the ESVEM trial.

The Myocarditis Treatment Trial: design, methods and patients enrollment.

The Myocarditis Treatment Trial was a multicentre clinical trial conducted to determine the efficacy of immunosuppressive therapy for treatment of biopsy-documented myocarditis, and to improve understanding of the immunological mechanisms in the development of myocarditis. Thirty-one centres screened 2305 patients with unexplained heart failure, and 2233 patients underwent an endomyocardial biopsy which provided adequate tissue for diagnosis. Those with a positive biopsy and a left ventricular ejection fraction (LVEF) less than 45% were randomly assigned to receive immunosuppressive therapy plus conventional drug therapy for congestive heart failure (66 patients) or conventional therapy only (45 patients) for 24 weeks. For 28 additional weeks all patients received conventional therapy only. In addition to diagnostic and clinical data, serum and myocardial tissue for immunological marker analysis and histopathologic evaluation were collected at baseline and at 12, 28 and 52 weeks after randomization. The primary analysis of efficacy was designed as a comparison of the mean increase in LVEF at week 28 between treatment limbs. Secondary objectives were to evaluate survival differences, and changes in the histopathology of the disease and immunological markers. Randomized patients were relatively young (mean age, 42.0 years +/- 13.8 standard deviation (sd) and entered the Trial with a mean LVEF percent of 24.3 +/- 10.1 sd) and mean exercise treadmill duration of 9.4 (+/- 5.3 sd) minutes. The incidence of biopsy-documented myocarditis was low (9.6%). The analyses of outcome and immunological data are reported elsewhere.

Significance and incidence of concordance of drug efficacy predictions by Holter monitoring and electrophysiological study in the ESVEM Trial. Electrophysiologic Study Versus Electrocardiographic Monitoring.

BACKGROUND: Selection of antiarrhythmic therapy may be based on either suppression of spontaneous ventricular arrhythmias assessed by Holter monitoring or by suppression of inducible ventricular arrhythmias during electrophysiological study. This study examines the frequency and significance of concordance of these two approaches in the Electrophysiologic Study Versus Electrocardiographic Monitoring (ESVEM) trial. METHODS AND RESULTS: Twenty-four-hour Holter monitoring was performed in patients randomized to the electrophysiology limb of the ESVEM study at the time of the first drug trial and at the time of an effective drug trial. Holter monitors were available in 65% (146/226) of patients at the time of the first drug trial and in 93% (100/108) of patients at the time of an electrophysiology study predicting drug efficacy. There were no clinical differences between patients who had and those who did not have a Holter monitor. At the time of the first drug trial, concordance of Holter and electrophysiological predictions of drug efficacy was observed in 46% of patients (both techniques predicted efficacy in 23%; neither predicted efficacy in 23%). Discordant results were observed in 54% (Holter suppression without electrophysiological suppression in 44%; electrophysiological suppression without Holter suppression in 10%). At the time of an electrophysiology study predicting drug efficacy, 68 of the 100 patients without inducible ventricular tachyarrhythmias also had suppression of spontaneous ventricular arrhythmias on the Holter recorded at the time of the electrophysiological study. Neither arrhythmia recurrence nor mortality was significantly different in patients with suppression of both inducible and spontaneous ventricular arrhythmias compared with those with only suppression of inducible arrhythmias. Comparison of patients with suppression of both inducible and spontaneous ventricular arrhythmias with the 188 patients in the Holter limb, in whom efficacy was predicted by Holter monitoring only, revealed no difference in outcome. CONCLUSIONS: In this population, (1) there is frequent discordance in prediction of drug efficacy and inefficacy between electrophysiological study and Holter monitoring; (2) a requirement to fulfill both Holter and electrophysiological efficacy criteria reduces the number of patients with an efficacy prediction; and (3) suppression of both spontaneous ventricular ectopy and inducible ventricular tachyarrhythmias does not identify a group with better outcome.

Cost of initial therapy in the Electrophysiological Study Versus ECG Monitoring trial (ESVEM).

BACKGROUND: Patients randomized to either serial electrophysiological testing (EPS) or serial Holter monitoring (HM) to guide antiarrhythmic therapy for life-threatening ventricular arrhythmias had equivalent rates of mortality and arrhythmia recurrence in the ESVEM study. This report analyzes the effects of EPS, HM, and clinical factors on the charges for initial evaluation and management of patients with life-threatening ventricular arrhythmias. METHODS AND RESULTS: Ten of 14 clinical centers participating in ESVEM provided bills from the initial hospitalization for randomized patients. Predictors of charges (1991 dollars) were analyzed by linear regression after logarithmic transformation. Initial hospital charge data were obtained for 286 patients randomized in ESVEM (88% of patients eligible for this substudy, 59% of all ESVEM patients). Patients with charge data were somewhat more likely to be older, to be female, and to have failed previous antiarrhythmic drug therapy at study entry and were less likely to have a drug predicted effective after randomization. Mean overall hospital charges were $35,986 (SD, $32,628) with a median of $24,532 (interquartile range, $16,126 to $43,593). Prerandomization patient characteristics generally had insignificant effects on charges, with the exception of presentation with resuscitated sudden death (28% increase in charges, P = .01) and heart failure (26% increase in charges, P = .02). Patients randomized to EPS had higher mean charges for evaluation ($42,002 versus $29,970, P = .0015) as well as more drug trials (3.0 versus 2.1, P = .0001) and a longer hospital stay (19.6 versus 13.9 days, P = .0007). In a multivariate regression model, failure to find an effective drug (P = .0001), the number of drug trials (P = .0001), and resuscitated sudden death as the presenting arrhythmia (P = .0001) were the only independent predictors of higher initial charges. CONCLUSIONS: (1) Initial hospital charges are significantly higher for EPS-guided than HM-guided therapy. (2) The higher charges for EPS-guided therapy were due to a greater number of drug trials and a lower probability of finding an effective drug. (3) Failure to find an effective drug, a larger number of drug trials, and a history of resuscitated sudden death independently predict higher charges.