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Biomedical subjects

L B Mitchell

Publications and source records attributed to L B Mitchell.

At least 55 records · Page 3Linked to original sources

Treatment of ventricular arrhythmias after recovery from myocardial infarction.

Demonstrated associations between postmyocardial infarction ventricular arrhythmias and a higher subsequent risk of both sudden and all-cause mortality have prompted a search for effective and safe treatment modalities. Recently completed clinical trials have provided a rationale for treatment recommendations in some specific settings. Beta-blocking therapy is recommended for postinfarction patients with frequent or complex ventricular premature beats. In contrast, calcium antagonist therapy is not helpful in these cases, and Class I antiarrhythmic therapy is actually harmful. Early indications of benefit from Class III antiarrhythmic therapies, particularly amiodarone, are under evaluation in large trials. Patients with sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) occurring late after myocardial infarction require therapy. Viable therapeutic methods include individualized antiarrhythmic therapy selected by the noninvasive approach, individualized antiarrhythmic therapy selected by the invasive approach, empiric amiodarone therapy, transcatheter or surgical ablative therapy (for VT), and use of an implantable cardioverter defibrillator. Clinical trial data have yet to determine which of these approaches is most effective under which circumstances. Postinfarction patients with nonsustained VT are the focus of several ongoing treatment trials. Early data suggest that risks requiring specific therapy are reached only by those patients who also have significant left ventricular dysfunction. The presence of inducible sustained ventricular tachycardia at an electrophysiologic study may further risk stratify such patients. High-risk patients with nonsustained ventricular tachycardia, left ventricular dysfunction, and inducible sustained ventricular tachycardia should participate in ongoing clinical trials. In the absence of this opportunity, intensive treatment should be considered.

Anti-Arrhythmia Agents↗

Canadian Implantable Defibrillator Study (CIDS): study design and organization. CIDS Co-Investigators.

The Canadian Implantable Defibrillator Study (CIDS) is an on-going randomized multicenter clinical trial that compares implantable cardioverter-defibrillator (ICD) therapy against amiodarone in patients with prior cardiac arrest or hemodynamically unstable ventricular tachycardia. Eligible patients are equally randomized to receive or not receive an ICD as initial management. Those not receiving an ICD receive amiodarone. All patients are seen in follow-up every 6 months. The primary outcome event cluster is arrhythmic death or any other death occurring within 30 days of therapy initiation. Secondary outcomes are all-cause mortality and nonfatal occurrences of ventricular tachycardia or fibrillation. The goal of the study is to recruit 400 patients over 4 years. All patients will be followed to the end of the year. This will result in an 80% chance of detecting a reduction in arrhythmic death of 58% by ICD if such a difference in truth exists. Recruitment began in October 1990 and 184 patients have been enrolled to date.

Amiodarone↗

A prospective randomized comparison of autodecremental pacing to burst pacing in device therapy for chronic ventricular tachycardia secondary to coronary artery disease.

A number of modes of antitachycardia pacing therapies are available in the newer generations of implantable cardioverter/defibrillators. The efficacy of synchronized burst overdrive pacing for the termination of induced and spontaneous monomorphic ventricular tachycardia (VT) was compared with synchronized autodecremental (ramp) pacing in 21 patients who received an implantable antitachycardia pacemaker/cardioverter/defibrillator for treatment of recurrent sustained monomorphic VT. Patients undergoing serial noninvasive VT induction studies after device implantation were prospectively randomized to receive trials of burst or ramp pacing therapies in a crossover study design. Antitachycardia pacing therapies were equally efficacious in treating induced VT (68% for ramp, 76% for burst pacing trials). The efficacy of ramp (93%) and burst (96%) pacing therapies was significantly higher in terminating spontaneously occurring episodes of VT than in terminating induced episodes (p = 0.001). The incidence of tachycardia acceleration was similar for both modes of pacing. The incidence of VT acceleration was lower for spontaneously occurring episodes of VT (0.01%) than for induced episodes of VT (6%, p < 0.01). Thus, antitachycardia pacing is an effective therapy for episodes of monomorphic VT, and the risk of accelerating VT to a hemodynamically unstable form is low. Antitachycardia pacing therapies are more effective against spontaneously occurring episodes than induced episodes of VT. Differences in tachycardia cycle length and duration may contribute to these effects.

Adult↗

Characteristics of patients with nonfatal cardiac arrest 3 to 180 days after acute myocardial infarction.

Patients who survive a tachyarrhythmic cardiac arrest in the first 6 months after acute myocardial infarction (AMI) are at risk for recurrent arrests, but the magnitude, timing and characteristics of this phenomenon are unknown. This study characterizes the nature of recurrent tachyarrhythmic cardiac arrests in the absence of reversible factors or new myocardial necrosis in patients between 3 and 180 days after AMI. We retrospectively assessed 28 patients (mean age 61 +/- 12 years) who survived an initial cardiac arrest a median of 10 days after AMI. Mean left ventricular ejection fraction was 36 +/- 9%. Fourteen patients (50%) had at least 1 recurrence of cardiac arrest, and 10 had > 2 arrests. Almost all (92%) recurrent cardiac arrests occurred within 5 days of the preceding arrest, and the high-risk periods were similar after the first, second or third cardiac arrest. Very fast ventricular tachycardia (mean cycle length 212 +/- 30 ms) was the documented responsible arrhythmia in 44 of 51 cardiac arrests. The morphology was either polymorphic, monomorphic or sinusoidal. No clinical or laboratory values could be found that predicted whether a patient would have a recurrent arrest. Nineteen patients (68%) survived to leave the hospital and have been followed for up to 96 months. For these, actuarial 5-year overall survival was 76% and actuarial 5-year arrhythmia-free probability was 80%. Thus, patients who survive a cardiac arrest in the first 6 months after AMI are at high risk of recurrent cardiac arrest for a further 5 days, and the arrests are due to characteristically fast ventricular tachycardias.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗

Risks of developing supraventricular and ventricular tachyarrhythmias after implantation of a cardioverter-defibrillator, and timing the activation of arrhythmia termination therapies.

The clinical courses of 39 consecutive recipients (mean age 61 +/- 12 years, and mean left ventricular ejection fraction 0.32 +/- 0.15) of an automatic implantable cardioverter-defibrillator (ICD) were examined to determine the risks of developing ventricular tachycardia (VT) and supraventricular tachyarrhythmias (SVT) after surgery, with ventricular response rates fulfilling ICD detection criteria. ICD system leads were implanted by thoracotomy in 25 patients and by using nonthoracotomy lead systems in 14. Six patients (18%) developed SVT after surgery, whereas 14 (36%) developed sustained VT. The median times to the development of both SVT and VT were 2 days. By actuarial analysis, the probability of developing VT after surgery was significantly greater than that of SVT during hospitalization (p = 0.04). This significant excess of postoperative VT over SVT was most marked in patients aged < or = 61 years, those who received nonthoracotomy rather than epicardial lead systems, those who presented with VT rather than ventricular fibrillation, and those who received > 20 intraoperative defibrillation shocks. These observations recommend the activation of ICD therapies immediately after implantation.

Age Factors↗

Comparison of biphasic and monophasic shocks for defibrillation using a nonthoracotomy system.

A comparison of defibrillation thresholds was made using biphasic and monophasic shocks delivered by a nonthoracotomy lead system in 2 clinically distinct groups of patients. The first group were patients receiving an implantable cardioverter-defibrillator who were studied before surgery with their chests closed. The second group were patients undergoing coronary artery bypass grafting (CABG) who were studied before surgery with their chests open but reapproximated. Biphasic defibrillation thresholds (stored energy) were significantly (p < 0.001) less than monophasic ones in subjects with the implantable cardioverter-defibrillator (12.3 +/- 5.3 vs 21.1 +/- 9.3 J) or CABG (14.6 +/- 7.1 vs 24.2 +/- 12.6 J). These values are less than were previously reported with a similar nonthoracotomy lead configuration. There were no significant differences between the 2 groups in all measurements derived from corresponding shock waveforms, although impedance tended to be greater in patients with CABG. However, subjects with CABG had greater left ventricular ejection fractions and did not have history of potentially lethal ventricular arrhythmias. Despite these differences, the conclusion that biphasic shocks are more effective would have been made in a study of either group alone. It is concluded that patients with CABG who have not had preceding potentially lethal ventricular arrhythmias may be a potential source of surrogate subjects for defibrillation research such as epicardial mapping, which requires that the chest be open.

Coronary Artery Bypass↗

Infarct artery patency predicts outcome of serial electropharmacological studies in patients with malignant ventricular tachyarrhythmias.

BACKGROUND: Surviving myocardial cells near the infarct border zone form the arrhythmogenic substrate for sustained ventricular tachycardia (VT) in humans. Infarct-related artery (IRA) patency may modulate the electrophysiological function of this arrhythmogenic substrate and its response to antiarrhythmic drug therapy. We postulated that effective antiarrhythmic drug therapy selected during serial electrophysiological studies in patients with VT after a myocardial infarction would be identified more frequently when the IRA is patent than when chronically occluded. METHODS AND RESULTS: Consecutive patients (n = 64) with documented coronary artery disease and remote myocardial infarction presenting with spontaneous sustained VT or ventricular fibrillation (VF) were studied. These patients underwent 4 +/- 2 electropharmacological studies identifying effective antiarrhythmic drug therapy in 16 (25%) patients. Drug responders did not differ significantly from nonresponders in demographic, electrocardiographic, angiographic, or hemodynamic measurements. A patent IRA was associated with antiarrhythmic drug response significantly more frequently than was an occluded IRA (45% versus 9%, p = 0.001). Patency of the IRA was the only independent predictor of response to antiarrhythmic drug therapy in this study population. The sensitivity and specificity of using a patent IRA to predict successful drug testing were 81% and 67%, respectively. CONCLUSIONS: The outcome of electropharmacological studies was predicted by the patency of the IRA. A patent IRA was associated with a greater probability of finding effective drug therapy.

Aged↗

Electrocardiographic correlates of spontaneous termination of ventricular tachycardia in patients with coronary artery disease.

BACKGROUND: In vitro studies have reported that beat-to-beat variance in tachycardia cycle length and in conduction and repolarization properties can result in spontaneous termination of reentrant arrhythmias. The purpose of this study was to define the ECG patterns associated with spontaneous termination of ventricular tachycardia in humans late after myocardial infarction. METHODS AND RESULTS: The QRS durations, QT intervals, and cycle lengths were measured on a beat-to-beat basis during episodes of sustained and spontaneously terminating ventricular tachycardias (VT) induced at antiarrhythmic drug-free and drug-assessment electrophysiological studies. Twenty-six patients were studied. Four categories of inducible ventricular tachycardia were studied: inducible sustained ventricular tachycardia in an antiarrhythmic drug-free state, spontaneously terminating ventricular tachycardia in an antiarrhythmic drug-free state, sustained ventricular tachycardia on antiarrhythmic therapy, and spontaneously terminating ventricular tachycardia on antiarrhythmic therapy. The ECG patterns that were statistically related to spontaneous termination of ventricular tachycardia included impingement of the QTP interval on the tachycardia cycle length (P < .001) both in the presence and absence of drugs, transient shortening of QRS just before termination, and paradoxical prolongation of QTP after abrupt shortening of ventricular tachycardia cycle length. In addition, greater beat-to-beat variances in tachycardia cycle lengths, QT intervals, and QRS durations were statistically associated with spontaneously terminating ventricular tachycardia. These ECG patterns did not occur during sustained episodes of ventricular tachycardia during the antiarrhythmic drug-free state or during ineffective antiarrhythmic drug therapy. CONCLUSIONS: A dynamic interplay between QRS duration, QT interval, and cycle length of tachycardia and their variances are associated with spontaneous termination of ventricular tachycardia in humans late after infarction. This study of ECG changes associated with spontaneous termination of ventricular tachycardia provides insight into potential mechanisms of antiarrhythmic drug efficacy.

Anti-Arrhythmia Agents↗

Myocardial uptake and pharmacodynamics of procainamide in patients with coronary heart disease and sustained ventricular tachyarrhythmias.

Little information is available currently regarding the time course of myocardial accumulation and the onset of the electrophysiologic effects of antiarrhythmic drugs in humans. The myocardial uptake and pharmacodynamics of the antiarrhythmic drug, procainamide, were studied during i.v. infusion in nine patients with ventricular tachycardia undergoing electrophysiologic study. Myocardial procainamide uptake was determined by serial measurements of arterial-coronary sinus drug concentration differences and measurement of coronary sinus blood flow during a 50-min procainamide infusion. The myocardial uptake of procainamide was 10 +/- 4% (mean +/- S.D.) of the total dose at 50 min. Coronary sinus procainamide concentrations equilibrated with arterial concentrations within 30 min of the start of the infusion. However, peripheral venous procainamide concentrations did not reach equilibrium with the arterial compartment during the 50-min drug infusion. Changes in the QRS duration, ventricular conduction time, QTc and ventricular refractory periods correlated in a linear fashion with changes in the plasma procainamide concentrations. The slopes of the arterial and coronary sinus concentration-effect relationships were similar and significantly greater than the slopes of the peripheral venous concentration-effect relationships (P < .05). Thus, procainamide equilibrates rapidly, but not instantaneously, in the myocardium. Short-term electrophysiologic effects correlate best with the arterial and coronary sinus drug concentrations. During this period, venous procainamide concentrations do not accurately reflect the myocardial concentration, effects or the eventual steady-state relationships.

Aged↗

Use-dependent electrophysiologic effects of amiodarone in coronary artery disease and inducible ventricular tachycardia.

Amiodarone produces use-dependent block of cardiac sodium channels in vitro. This study assessed whether similar use-dependent block occurred in 19 patients with coronary artery disease and inducible, sustained, monomorphic ventricular tachycardia treated with amiodarone. Beat-to-beat measurements of ventricular paced QRS durations during 12-beat trains at cycle lengths of 700, 600, 400 and 300 ms were analyzed at a baseline antiarrhythmic drug-free study and after 2 and 10 weeks of amiodarone therapy. At the drug-free study, there were no significant changes in paced QRS durations within the 12-beat trains at any pacing cycle lengths. After 2 and 10 weeks of amiodarone therapy, progressive prolongation of paced QRS durations occurred over the 12-beat trains at pacing cycle lengths of 600, 400 and 300 ms (p less than 0.05). Significant changes in QRS duration were not observed at a pacing cycle length of 700 ms. This progressive prolongation in QRS duration can be fitted as a function of beat number to a monoexponential equation and occurred with an onset time constant of 1.02 +/- 0.41 beats (306 +/- 122 ms) at a pacing cycle length of 300 ms. The magnitude of QRS prolongation increased as the pacing cycle length was shortened. The magnitudes of QRS prolongation were similar after 2 and 10 weeks of amiodarone therapy. In conclusion, use-dependent prolongation in QRS duration occurs at rapid pacing cycle lengths in humans receiving amiodarone.

Amiodarone↗

Comparison of atrial overdrive pacing with and without extrastimuli for termination of atrial flutter.

Atrial overdrive pacing has been successfully used to terminate atrial flutter. This study compared the efficacy of atrial extrastimuli following a rapid pacing train to overdrive pacing without atrial extrastimuli for the termination of atrial flutter. Patients were randomized to treatments of short or long burst atrial overdrive pacing or atrial overdrive pacing followed by atrial extrastimuli in a crossover study design. A total of 22 patients (73%) had successful conversion of atrial flutter to sinus rhythm. The success rates in patients exposed to each therapy, including crossover therapies, were 62% with the atrial extrastimuli method, 8% with the short burst pacing method, and 8% with the long burst pacing method (p less than 0.001). Transient atrial fibrillation developed in 15 patients and in 9 of these this arrhythmia preceded conversion to sinus rhythm. Sustained atrial fibrillation was induced in 3 additional patients but never with the atrial extrastimuli method. In conclusion, the method of delivering atrial extrastimuli after a rapid pacing train is highly efficacious for the termination of atrial flutter. Furthermore, this method is more effective than atrial overdrive pacing methods delivered at the same pacing cycle length. These observations have important implications for the programming of antitachycardia pacemakers.

Aged↗

Effects of left ventricular dysfunction on the circadian variation of ventricular premature complexes in healed myocardial infarction.

Circadian variation in the onset of cardiovascular events including sudden cardiac death, myocardial infarction and ventricular arrhythmias has been described. The effect of left ventricular (LV) dysfunction on the circadian variation of ventricular premature complex (VPC) frequency was evaluated in 132 patients with frequent VPCs and reduced LV function after myocardial infarction. Patients were prospectively divided in 2 groups based on LV ejection fraction (EF) (those with LVEF less than or equal to 0.30, and those with LVEF between 0.30 and 0.45). Median hourly VPC frequencies and heart rates were compared between the 2 groups. Subgroup analyses based on treatment with beta-adrenoceptor blocking agents and on New York Heart Association functional class were also performed. In patients with LVEF greater than 0.30, a distinct circadian variation of VPCs, and the expected morning increase in VPC frequency were present. In contrast, a distinct circadian variation of VPCs was absent in patients with LVEF less than or equal to 0.30. A circadian variation of VPC frequency was also absent in patients with severe symptomatic congestive heart failure (New York Heart Association class III-IV). Treatment with beta-adrenoceptor blocking agents was associated with a loss of the circadian variation of VPC frequency. The circadian variation of heart rate was also blunted in the group treated with beta-adrenoceptor blocking agents. The proportion of subjects manifesting a positive correlation between heart rate and VPC frequency was lower in subjects with LVEF less than or equal to 0.30 (26%) than in those with LVEF greater than 0.30 (46%) (p less than 0.05). Thus, circadian variation of VPC frequency is absent in patients with severe LV dysfunction.

Adrenergic beta-Antagonists↗

Electrocardiographic body surface mapping in patients with ventricular tachycardia. Assessment of utility in the identification of effective pharmacological therapy.

BACKGROUND: Body surface maps of net QRST deflection areas (isointegrals) reflect regional ventricular repolarization properties. Vulnerability to ventricular tachyarrhythmias is associated with maps that feature multiple islands (extrema) of positive and negative values; such maps reflect regional disparity of ventricular recovery properties. The value of body surface mapping in prediction of the efficacy of antiarrhythmic therapy for ventricular tachyarrhythmias has not been determined. METHODS AND RESULTS: Isointegral ECG body surface mapping was performed in 51 patients with inducible ventricular tachycardia having programmed stimulation studies at baseline and after oral quinidine therapy. The degree of nondipolarity of QRST isointegral distribution was expressed by the number of extrema and by the percentage contribution of nondipolar eigenvectors after Karhunen-Loeve transformation. QRST isointegral nondipolarity was greater in ventricular tachycardia patients than in 51 age- and sex-matched normal subjects expressed as mean number of extrema (4.1 +/- 2.8 versus 2.0 +/- 0.2, respectively), mean eigenvector-determined nondipolar content percentages (12.4 +/- 10.1% versus 4.5 +/- 4.9%), prevalence of abnormal numbers of extrema (63% versus 4%), or prevalence of abnormal nondipolar content percentages (33% versus 4%) (each p less than 0.01). Quinidine prevented ventricular tachycardia induction in 14 patients. Patients for whom quinidine was or was not effective had similar nondipolarity indexes at baseline. However, maps on quinidine differed as a function of antiarrhythmic efficacy. Although effective therapy produced no significant mean changes in nondipolarity, ineffective therapy increased the number of extrema compared with baseline (5.4 +/- 3.4 versus 3.8 +/- 2.5, respectively) (p = 0.002). Individually, 43% of patients on effective therapy had drug-induced decreases in numbers of extrema compared with 14% of those on ineffective therapy (p = 0.02). Furthermore, 29% of patients on effective therapy showed drug-induced increases in numbers of extrema compared with 62% of those on ineffective therapy (p = 0.03). CONCLUSIONS: QRST isointegral body surface mapping shows promise as a noninvasive measure of drug efficacy in patients with ventricular tachycardia.

Anti-Arrhythmia Agents↗

Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone.

BACKGROUND: Patients with a history of class Ia drug-induced torsade de pointes have been treated with chronic amiodarone without recurrence of torsade de pointes despite comparable prolongation of the QT interval. We hypothesized that in such patients, class Ia drugs cause nonhomogeneous prolongation of cardiac repolarization times, whereas amiodarone causes homogeneous prolongation of cardiac repolarization times. METHODS AND RESULTS: Thirty-eight consecutive patients who received both class Ia drug therapy and chronic amiodarone therapy were evaluated. Standard 12-lead ECGs at baseline and during each therapy were used to calculate precordial QT interval dispersion (maximum QT in leads V1 through V6 minus minimum QT leads V1 through V6) as a measure of regional variabilities in ventricular repolarization times. Nine of these patients had torsade de pointes during class Ia drug therapy. In these nine patients, class Ia drug therapy and amiodarone significantly prolonged the maximum QT interval to comparable extents. However, class Ia drug therapy but not amiodarone therapy significantly increased precordial QT interval dispersion (101 +/- 37 versus 49 +/- 26 msec; baseline, 44 +/- 12 msec; p = 0.002). In the 29 patients without class Ia drug-induced torsade de pointes, neither class Ia drug therapy nor amiodarone therapy significantly increased QT interval dispersion (50 +/- 6 versus 69 +/- 7 msec; baseline, 54 +/- 5 msec). None of the patients with class Ia drug-induced torsade de pointes had recurrent torsade de pointes during chronic amiodarone therapy. CONCLUSIONS: An increase in regional QT interval dispersion during class Ia antiarrhythmic drug therapy is associated with torsade de pointes. Chronic amiodarone therapy in patients with a history of class Ia drug-induced torsade de pointes produces comparable maximum QT interval prolongation but does not increase QT interval dispersion. This characteristic may explain its apparent safe use in patients with a history of class Ia drug-induced torsade de pointes.

Aged↗

Drug therapy of ventricular tachycardia: a cost comparison of randomized noninvasive and invasive approaches.

OBJECTIVE: Economic evaluation of noninvasive (suppression of ventricular arrhythmias detected by ambulatory monitoring) and invasive (suppression of arrhythmias induced by programmed stimulation) approaches to antiarrhythmic drug selection for ventricular tachyarrhythmias. DESIGN/SETTING: Randomized clinical trial/tertiary-care hospital. PATIENTS: Of 124 consecutive patients referred for treatment of symptomatic ventricular tachyarrhythmias, 57 consenting patients were eligible to have drug therapy selected by either noninvasive or invasive approaches. MEASUREMENTS: Costs of initial and follow-up (26 +/- 15 months) admissions for the two groups were compared. This economic evaluation also considered relative efficacies of the approaches using the primary outcome variable of symptomatic, sustained ventricular tachyarrhythmia recurrence (including sudden death). RESULTS: Initial hospitalization for therapy selection was less costly by the noninvasive approach ($6,869 +/- 4,019) than by the invasive approach ($13,164 +/- 6,740) (P less than 0.001). However, the noninvasive approach generated higher follow-up hospital costs ($9,204 +/- 9,217) than the invasive approach ($3,784 +/- 4,944) (P = 0.01). Thus, total hospital costs of the noninvasive ($16,073 +/- 9,423) and invasive approaches ($16,949 +/- 7,174) were equivalent. The two-year actuarial probability of a recurrent, sustained, symptomatic ventricular tachyarrhythmia was greater in noninvasive (0.50 +/- 0.10) than in invasive (0.20 +/- 0.08) approach patients (P = 0.02). CONCLUSIONS: The lower initial hospital costs of the noninvasive approach are offset by greater follow-up costs. Within two years the costs of the two approaches are equivalent. Thus, greater antiarrhythmic efficacy can be achieved by the invasive approach to drug selection without increasing total hospital costs.

Anti-Arrhythmia Agents↗

Mortality and morbidity in patients receiving encainide, flecainide, or placebo. The Cardiac Arrhythmia Suppression Trial.

BACKGROUND AND METHODS: In the Cardiac Arrhythmia Suppression Trial, designed to test the hypothesis that suppression of ventricular ectopy after a myocardial infarction reduces the incidence of sudden death, patients in whom ventricular ectopy could be suppressed with encainide, flecainide, or moricizine were randomly assigned to receive either active drug or placebo. The use of encainide and flecainide was discontinued because of excess mortality. We examined the mortality and morbidity after randomization to encainide or flecainide or their respective placebo. RESULTS: Of 1498 patients, 857 were assigned to receive encainide or its placebo (432 to active drug and 425 to placebo) and 641 were assigned to receive flecainide or its placebo (323 to active drug and 318 to placebo). After a mean follow-up of 10 months, 89 patients had died: 59 of arrhythmia (43 receiving drug vs. 16 receiving placebo; P = 0.0004), 22 of nonarrhythmic cardiac causes (17 receiving drug vs. 5 receiving placebo; P = 0.01), and 8 of noncardiac causes (3 receiving drug vs. 5 receiving placebo). Almost all cardiac deaths not due to arrhythmia were attributed to acute myocardial infarction with shock (11 patients receiving drug and 3 receiving placebo) or to chronic congestive heart failure (4 receiving drug and 2 receiving placebo). There were no differences between the patients receiving active drug and those receiving placebo in the incidence of nonlethal disqualifying ventricular tachycardia, proarrhythmia, syncope, need for a permanent pacemaker, congestive heart failure, recurrent myocardial infarction, angina, or need for coronary-artery bypass grafting or angioplasty. CONCLUSIONS: There was an excess of deaths due to arrhythmia and deaths due to shock after acute recurrent myocardial infarction in patients treated with encainide or flecainide. Nonlethal events, however, were equally distributed between the active-drug and placebo groups. The mechanisms underlying the excess mortality during treatment with encainide or flecainide remain unknown.

Actuarial Analysis↗

Drug response at electropharmacologic study in patients with ventricular tachyarrhythmias: the importance of ventricular refractoriness.

The clinical and electrophysiologic predictors of successful antiarrhythmic drug therapy for patients with inducible ventricular tachycardia were evaluated in 59 consecutive patients undergoing serial electropharmacologic trials. Structural heart disease was less frequently present in patients for whom effective therapy was found (p less than 0.05). The presence of coronary artery disease and a history of prior myocardial infarction were significantly more frequently present in patients for whom antiarrhythmic drug therapy could not be found (p less than 0.05). The corrected QT interval and ventricular effective refractory period measured at a pacing cycle length of 400 ms were significantly shorter in responders compared with nonresponders (QT interval 428 +/- 52 versus 460 +/- 59 ms; ventricular effective refractory period 237 +/- 28 versus 254 +/- 24 ms; (p less than 0.05). In addition, the interelectrogram coupling interval of the ventricular extrastimulus initiating ventricular tachycardia was significantly shorter in responders compared with nonresponders (223 +/- 37 versus 251 +/- 33 ms; p = 0.003). Logistic regression analysis identified a short ventricular interelectrogram coupling interval (p less than 0.01) and absence of prior myocardial infarction (p less than 0.05) as the only independent predictors of antiarrhythmic drug suppression of the induction of ventricular tachycardia. Greater drug-induced increments in the ventricular effective and functional refractory periods were observed in responders than in nonresponders as was the shortest ventricular interelectrogram coupling interval. Thus, baseline electrophysiologic measurements identify patients with inducible ventricular tachycardia who are likely to respond to antiarrhythmic drug therapy. Furthermore, these patients demonstrate greater drug-induced electrophysiologic changes.

Anti-Arrhythmia Agents↗

Drug therapy for ventricular tachyarrhythmias: how many electropharmacologic trials are appropriate?

To determine how many electropharmacologic drug trials should be performed to select therapy for patients with ventricular tachyarrhythmias, the outcome of 150 consecutive patients with inducible ventricular tachyarrhythmias undergoing serial electropharmacologic testing was examined. The probability of identifying predicted effective therapy (inductive of fewer than five ventricular responses with three ventricular extrastimuli at three pacing cycle lengths) and the probability of that therapy preventing sustained ventricular tachyarrhythmia recurrences were determined as a function of the number of preceding trials. The probability ( +/- SE) of identifying predicted effective therapy by the first trial (0.23 +/- 0.03) was significantly higher than that of the second (0.09 +/- 0.04), third (0.08 +/- 0.04) and fourth (0.05 +/- 0.04) trials (p = 0.001). No patient had predicted effective therapy identified by subsequent trials. The 2 year actuarial probability of freedom from sustained ventricular tachyarrhythmias on predicted effective therapy was higher for the first (0.79 +/- 0.08), second (0.73 +/- 0.13) and third (0.86 +/- 0.13) trials than for the fourth (0.33 +/- 0.27) trial (p = 0.02). Thus, the probability of selecting therapy with long-term efficacy was highest for the first trial (0.18), intermediate for the second (0.07) and third (0.07) trials and lowest for the fourth (0.02) and subsequent (0.00) trials. Accordingly, the electropharmacologic approach to therapy selection should be abandoned after three unsuccessful trials.

Actuarial Analysis↗