Thomas A. Buckingham

Long-term follow-up of asymptomatic healthy subjects with frequent and complex ventricular ectopy.

Abstract From 1973 to 1983 we followed 73 asymptomatic healthy subjects who were discovered to have frequent and complex ventricular ectopy. Ventricular ectopy in these subjects was measured by 24-hour ambulatory electrocardiography, which showed a mean frequency of 566 ventricular ectopic beats per hour (range, 78 to 1994), with multiform ventricular ectopic beats in 63 per cent, ventricular couplets in 60 per cent, and ventricular tachycardia in 26 per cent. Asymptomatic healthy status was confirmed by extensive noninvasive cardiologic examination, although cardiac catheterization of a subsample of subjects disclosed serious coronary artery disease in 19 per cent. Follow-up for 3.0 to 9.5 years (mean, 6.5) was accomplished in 70 subjects (96 per cent) and documented one sudden death and one death from cancer. Calculation of a standardized mortality ratio (Monsons U.S. data, 8th revision) for 448 person-years of follow-up indicated that 7.4 deaths were expected, whereas 2 occurred (standardized mortalit...

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)

The effects of sampling site on the two-dimensional echo-Doppler determination of cardiac output

Cardiac output was measured by two-dimensional echocardiographic Doppler technique in 55 adult patients in the intensive care unit. Doppler cardiac output determinations were measured from four sites (suprasternal long axis of the ascending aorta, suprasternal long axis of the descending aortic, apical left ventricular outflow tract, and parasternal long axis of the main pulmonary artery) and were compared to cardiac output determined by thermodilution for a total of 101 observations (r = 0.84). Mean cardiac output was 5.3 L/min (range 1.8 to 9.5 L/min) by Doppler technique and 5.1 L/min (range 1.6 to 8.9 L/min) as measured by thermodilution. Correlation of Doppler cardiac output with thermodilution cardiac output gave r values of 0.85, 0.83, 0.90, and 0.81 from the ascending aorta, descending aorta, left ventricular outflow tract, and pulmonary artery, respectively. Averaging of data in patients in whom more than one determination was possible resulted in improved correlation (r = 0.94). Thus, cardiac output can be measured with reasonable accuracy by Doppler from a variety of sampling sites and averaging of data from more than one site may improve these results.

Systolic and Diastolic Function with Alternate and Combined Site Pacing in the Right Ventricle

We hypothesized that pacing at two ventricular sites simultaneously would activate the myocardium more rapidly and improve ventricular function. We studied the effect of pacing at the right ventricular outflow tract (RYOT) and the RV apex (EVA) on systolic and diastolic function. In 14 patients with a reduced systolic ejection fraction < 40% (mean EF 32%±4%)we measured RV pressures, left ventricular pressures, EF, cardiac output, peak dP/dt, peak negative dP/dt, and the time constant of relaxation, Tau, during intrinsic rhythm, atrial pacing and DVI pacing at the RVA, the RVOT, and both RV sites combined in random order. Repeated measures analysis of variance showed no significant differences in any of these parameters. The highest absolute values of dP/dt were observed during sinus rhythm and the lowest with RVA pacing. This parameter tended to improve progressively with pacing in the RVOT and at both sites. Peak negative dP/dt showed a similar nonsignificant trend. Conclusion: These data suggest that in patients with poor LV function, there may be subtle improvements in diastolic and systolic function with pacing in the RVOT and at combined sites in the RV compared to traditional RVA pacing.

Doppler echocardiographic assessment of the effect of varying atrioventricular delay and pacemaker mode on left ventricular filling

Pulsed Doppler echocardiography was used to study the timing and dynamics of left ventricular filling in 14 patients with permanent dual-chamber programmable pacemakers. Pacemakers were programmed to atrial sensed (VDD) mode and atrial-ventricular sequential paced mode at low (DVI-L) and high (DVI-H) heart rates, and pulsed Doppler recordings of transmitral flow were analyzed at atrioventricular delays of 50 to 300 msec in each mode. There was a significant decrease in the one-third filling fraction in both VDD and DVI-L modes and a significant increase in DVI-H modes with increasing atrioventricular delay. The ratio of early filling area to atrial filling area was significantly lower at longer atrioventricular delays in both VDD and DVI-L modes. The time from pacemaker spike to mitral valve closure was highly significantly correlated with atrioventricular delay in VDD, DVI-L, and DVI-H modes (r = -0.92, p = 0.0001; r = -0.90, p = 0.0001; and r = -0.85, p = 0.0001, respectively) as was the diastolic filling time to a lesser extent (r = -0.73, p = 0.0001; r = -0.69, p = 0.0001; r = -0.61, p = 0.0001, respectively). Events reflecting atrial systole occurred at a later time in the cardiac cycle in the atrial paced vs the atrial sensed mode. Thus changes in atrioventricular delay and pacemaker mode in this group of patients are a strong determinant of the timing and dynamics of left ventricular filling.

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.

Signal-averaged electrocardiography in the time and frequency domains

The noninvasive signal-averaged electrocardiographic detection of late potentials correlates with the spontaneous occurrence of sustained ventricular tachycardia (VT). Frequency analysis of the electrocardiographic signal from the terminal QRS and ST segment also correlates with sustained VT. This study was designed to compare these 2 methods by analysis of signals recorded from the same hardware system. Signals were recorded from 234 patients with prior myocardial infarctions with a commercially available signal-averaging system. Patients were classified into 2 groups: group 1 consisted of 84 patients with VT and group 2 consisted of 150 patients without VT. In the frequency domain, magnitude and energy area ratios and peak ratios of the spectral plot from 20 to 50 Hz over 0 to 20 Hz were calculated for a 140-ms interval starting 60 ms after the beginning of the QRS. In the time domain, the duration of the filtered QRS was 121 +/- 29 ms for group 1 and 110 +/- 25 ms for group 2 (p less than 0.002). The duration of the terminal QRS less than 40 microV was 45 +/- 21 ms in group 1 and 36 +/- 18 ms in group 2 (p less than 0.001). The root-mean-square amplitude of the terminal 40 ms of the QRS was 25 +/- 24 microV in group 1 and 36 +/- 33 microV in group 2 (p less than 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

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.