Robert M. Redd

Effect of conduction defects on the signal-averaged electrocardiographic determination of late potentials

To determine the effect of cardiac conduction defects on the signal-averaged electrocardiogram (ECG) and on its ability to noninvasively identify patients predisposed to ventricular tachycardia (VT), standard 12-lead ECGs and signal-averaged ECGs were obtained in 213 patients with normal conduction and 186 patients with various conduction defects. Sustained VT was induced by programmed stimulation or occurred spontaneously in 122 patients. Two-way analysis of variance showed that conduction defects and VT were associated with changes in 3 signal-averaged ECG parameters: duration of the filtered QRS, duration of the terminal QRS under 40 microV and the mean amplitude of the terminal 40 ms of the QRS. Stepwise multiple logistic regression identified 3 variables that distinguished the patient with VT with a sensitivity of 62%, a specificity of 63% and a positive predictive accuracy of 63%. These 3 variables, listed in order of importance, were conduction defect score, duration of the filtered QRS and mean amplitude of the terminal 40 ms of the QRS. These data indicate that conduction defects have systematic effects on signal-averaged ECG parameters independent of those seen in patients predisposed to VT. These effects mandate the adjustment of the definitions of late potentials in the presence of conduction defects.

The hemodynamic benefit of differential atrioventricular delay intervals for sensed and paced atrial events during physiologic pacing

The ability to program different atrioventricular (AV) delay intervals for paced and sensed atrial events is incorporated in the design of some newer dual chamber pacemakers. However, little is known regarding the hemodynamic benefit of differential AV delay intervals or the magnitude of difference between optimal AV delay intervals for paced and sensed P waves in individual patients. In this study, Doppler-derived cardiac output was used to examine the optimal timing of paced and sensed atrial events in 24 patients with a permanent dual chamber pacemaker. The hemodynamic effect of utilizing separate optimal delay intervals for sensed and paced events compared with utilizing the same fixed AV delay interval for both was determined. The optimal delay interval during DVI (AV sequential) pacing and VDD (atrial triggered, ventricular inhibited) pacing at similar heart rates was 176 +/- 44 and 144 +/- 48 ms (p less than 0.002), respectively. The mean difference between the optimal AV delay intervals for sensed (VDD) and paced (DVI) P waves was 32 ms and was up to 100 ms in some individuals. The difference between optimal AV delay intervals for sensed and paced atrial events was similar in patients with complete heart block and those with intact AV node conduction. At the respective optimal AV delay intervals for sensed and paced P waves, there was no significant difference in the cardiac output during VDD compared with DVI pacing. However, cardiac output significant declined during VDD pacing at the optimal AV delay interval for a paced event and during DVI pacing at the optimal interval for a sensed event.(ABSTRACT TRUNCATED AT 250 WORDS)

Independent value of signal-averaged electrocardiography and left ventricular function in identifying patients with sustained ventricular tachycardia with coronary artery disease

To determine if the signal-averaged electrocardiographic detection of late potentials is an independent marker of sustained ventricular tachycardia (VT) in patients with documented chronic coronary artery disease (CAD), 57 patients underwent signal-averaged electrocardiography. Mean ejection fraction was 47 +/- 13% in the 14 patients with sustained VT and 56 +/- 19% in the 43 patients without VT (difference not significant). The sensitivity, specificity and accuracy of late potentials for detecting patients with VT were 64% (9 of 14), 79% (34 of 43), and 75% (43 of 57), respectively. Univariate analysis and stepwise logistic regression of angiographic and electrocardiographic variables identified late potentials as an independent marker of the patient with sustained VT. The odds ratio for late potentials to detect patients with prior sustained VT was 2.6. Six-month follow-up revealed a cardiac mortality rate of 11% and an arrhythmia event rate of 22% in patients with late potentials vs a cardiac mortality rate of 3% and an arrhythmia event rate of 13% in patients without late potentials. Thus, signal-averaged electrocardiographic detection of late potentials is useful in identifying patients with prior sustained VT independent of left ventricular function.

Hemodynamic benefit of atrioventricular synchrony: Prediction from baseline Doppler-echocardiographic variables

The purpose of this study was to determine if baseline Doppler-echocardiographic variables of systolic or diastolic function could predict the hemodynamic benefit of atrioventricular (AV) synchronous pacing. Twenty-four patients with a dual chamber pacemaker were studied. Baseline M-mode and two-dimensional echocardiograms were obtained and Doppler-echocardiographic measurements of mitral inflow and left ventricular outflow were made in VVI mode (single rate demand) and in VDD (atrial synchronous, ventricular inhibited) and DVI (AV sequentially paced) modes at AV intervals ranging from 50 to 300 ms. Forward stroke volume and cardiac output were determined in each mode at each AV interval from the left ventricular outflow tract flow velocities, and the percent increase in cardiac output over VVI mode was determined. M-mode measurements, including left ventricular end-diastolic dimension, shortening fraction and left atrial size and Doppler measurement of diastolic filling, including peak early velocity and percent atrial contribution, did not correlate with the percent increase in cardiac output during physiologic pacing. The stroke volume in VVI mode correlated significantly with the percent increase in cardiac output during physiologic pacing (r = -0.61, p less than 0.005 for VDD mode and r = -0.55, p less than 0.05 for DVI mode). Five of the 15 patients with VVI stroke volume less than 50 ml but none of the 9 patients with stroke volume greater than 50 ml had ventriculoatrial (VA) conduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Design of a multicenter randomized trial for the stroke prevention in atrial fibrillation study

Individuals with nonvalvular atrial fibrillation are at increased risk of stroke. The Stroke Prevention in Atrial Fibrillation Study is a 15-center randomized clinical trial examining the risks and benefits of low-intensity warfarin (prothrombin time of 1.3-1.8 times control) and aspirin (325 mg/day) in patients with constant or intermittent atrial fibrillation. Candidates for anticoagulation (group I) are randomized to receive warfarin in an open-label fashion, aspirin, or placebo; the last two treatments are given in a double-blind fashion. Warfarin-ineligible patients (group II) are randomized to receive aspirin or placebo in a double-blind fashion. Primary end points are ischemic stroke and systemic embolism. Secondary end points are death, transient ischemic attack, myocardial infarction, and unstable angina pectoris. Analysis is based on the intention-to-treat principle. The anticipated rate of primary end points in patients receiving placebo is 6%/yr. The sample size of 1,644 patients is based on a projected reduction in the rate of primary end points of 50% by warfarin and of 33% by aspirin (beta = 0.2, alpha = 0.05). Patient entry commenced in June 1987 and will continue for 3 years, with an additional year of follow-up. High-risk subsamples identified by clinical and echocardiographic criteria are sought prospectively.

Utility of ambulatory electrocardiography in detecting pacemaker dysfunction in the early postimplantation period

The value of ambulatory electrocardiography (AECG) in detecting pacemaker dysfunction before hospital discharge was assessed in 100 patients a mean of 1.2 days after pacemaker implantation. The incidence of permanent pacemaker dysfunction detected by AECG in the early postimplantation period, the frequency that pacemaker dysfunction detected by AECG was not detected by telemetric monitoring and the frequency that results of AECG led to pacemaker reprogramming before hospital discharge were determined. AECG detected at least 1 type of pacemaker dysfunction in 35% of patients and routine telemetry identified the abnormality in only 8% (p less than 0.001). Pacemaker dysfunction occurred in 42% of patients with dual-chamber devices and 27% of those with single-chamber devices (difference not significant). In the 35 patients who had pacemaker malfunction, a total of 50 instances of pacemaker dysfunction were detected. Failure of atrial capture occurred in 2% of patients, failure of atrial sensing in 9%, failure of atrial output in 1%, failure of ventricular capture in 8%, failure of ventricular sensing in 14%, failure of ventricular output due to myopotential inhibition in 11% and pacemaker-mediated tachycardia in 5%. The results of the AECG led to a clinical intervention in 22 patients (pacemaker reprogramming in 21 patients and lead repositioning in 1 patient) in whom no pacemaker dysfunction was suspected on the basis of telemetry or clinical symptoms. In conclusion, AECG provides additional benefit beyond that of routine telemetry monitoring in identifying pacemaker dysfunction in the early period after implantation.

Effect of ventricular function on the exercise hemodynamics of variable rate pacing.

To determine the effect of ventricular function on the exercise hemodynamics of variable rate pacing, 16 selected patients underwent paired, double-blind, randomized exercise tests in single rate demand (VVI) or variable rate (VVIR) pacing modes. Ejection fraction and cardiac index were determined by two-dimensional and Doppler echocardiography at baseline and during peak exercise. Baseline ejection fraction ranged from 14 to 73% and was less than 40% in 6 patients (Group 1) and greater than or equal to 40% in 10 patients (Group 2). Duration of exercise was longer during the VVIR mode (502 s) than during the VVI mode (449 s) (p less than 0.01) and unrelated to baseline ejection fraction. Heart rate during exercise increased 9% in the VVI mode and 35% in the VVIR mode (p less than 0.005). Cardiac index increased 49% in the VVI mode and 83% in the VVIR mode. Analysis of variance for repeated measures showed a significant effect of pacing mode (p less than 0.01) and exercise (p less than 0.001), but not baseline ejection fraction, on cardiac index. Baseline ejection fraction did not correlate with the increase in cardiac index in either pacing mode or with the difference in increase between modes. There was no significant difference between Groups 1 and 2 in exercise duration, peak heart rate-blood pressure (rate-pressure) product, baseline or peak heart rate or baseline or peak cardiac index. Therefore, in selected patients, VVIR pacing during exercise results in an increase in heart rate, duration of exercise and cardiac index that is unrelated to the degree of baseline left ventricular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of serial pulmonary function testing as an indicator of amiodarone toxicity.

A prospective study was conducted of 189 patients treated with amiodarone, maintained at doses of 400 to 800 mg/day and followed for up to 6 years. Only patients who had life-threatening ventricular arrhythmias unresponsive to conventional therapy were enrolled, and they underwent baseline pretreatment pulmonary function tests, with follow-up testing every 6 months. Morbidity and mortality statistics were confirmed by chart review and patient telephone interview. Of the 189 enrolled patients, 101 are alive, 84 are dead and 4 are lost to follow-up. Amiodarone-induced toxicity to the neurologic system, lungs, thyroid or liver was the primary or complicating cause of death in 12 of the 84 patients who died. The overall prevalence of all these forms of toxicity was 15%. Sixty-nine percent of the patients with amiodarone toxicity had pulmonary toxicity alone or combined with other forms of toxicity. Pulmonary function test abnormalities were noted at baseline in 75% of patients who had amiodarone-induced toxicity. The proportion of abnormal baseline pulmonary function tests was not significantly different among all toxic patients, pulmonary toxic patients and nontoxic patients. An evaluation of the decrease in pulmonary function over time could not distinguish patients who developed toxicity from those who did not. The observed incidence of pulmonary toxicity is consistent with published values; however, contrary to the findings of others, no statistically significant differences in pulmonary function at baseline or in changes over time were found between toxic and nontoxic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Serum digoxin concentrations during ethmozine antiarrhythmic therapy

The potential for pharmacokinetic drug interaction between ethmozine (moricizine HCl), a phenothiazine class I antiarrhythmic investigational drug, and digoxin was evaluated in 13 cardiac patients with normal renal function. Antiarrhythmic therapy was initiated in patients with potentially lethal (nonlife-threatening) ventricular arrhythmias (greater than 30 ventricular ectopic beats [VEB]/hr) who were receiving maintenance digoxin therapy for congestive heart failure and/or atrial fibrillation. Serum digoxin concentrations of patients were measured frequently by radioimmunoassay and plasma ethmozine concentrations by high-performance liquid chromatographic methods. Patients entered a short-term (4 weeks) single-blind, placebo controlled ethmozine protocol with an option to receive long-term (1 to 6 months) open-label maintenance ethmozine therapy. Ambulatory ECGs (48 hour) used to assess antiarrhythmic efficacy of ethmozine during each week of the short-term protocol showed that 77% of patients demonstrated greater than 90% mean hourly frequency suppression of all forms of ventricular ectopy. Serum digoxin concentrations during short-term ethmozine dosing showed a nonsignificant (p greater than 0.05) increase of 10% to 15% (mean 0.91 ng/ml to 1.13 ng/ml). The short-term protocol serum digoxin levels correlated closely with serum digoxin concentrations during placebo therapy (1st week, r = 0.90; 2nd week, r = 0.87). Serum digoxin concentrations were not significantly different (p greater than 0.05) from placebo values at the end of 1, 3, and 6 months of maintenance ethmozine therapy. Thus, we conclude that ethmozine administered in an antiarrhythmic efficacious dosage (10 mg/kg/day) showed no important clinical or statistically significant change in serum digoxin concentrations of cardiac patients with normal renal function.

Analysis of probability density function by programmed electrical stimulation

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