Double external direct-current shocks for refractory atrial fibrillation.

Encouraged by preliminary data using double external direct-current (DC) shocks in patients with atrial fibrillation refractory to single external DC shocks, we undertook a prospective study of all patients with atrial fibrillation of > 1-month duration using a shock sequence with (1) 1 shock of 200 J anterior-posterior, (2) 1 shock of 360 J anterior-posterior, (3) 1 shock of 360 J apex-anterior, and (4) double shocks with configurations 2 and 3 delivered almost simultaneously by 2 defibrillators. The double shocks appeared to be safe and restored sinus rhythm in approximately 2 of 3 of patients in whom DC cardioversion failed with single shocks.

Heart rate variability and head-up tilt testing in patients with syncope of undetermined etiology.

Indices of heart rate variability are non-invasive indicators of neural control of the heart. To investigate the significance of changes in heart rate variability in neurally mediated syncope, we performed head-up tilt testing in 45 patients with syncope of undetermined etiology. Seventeen patients showed a negative response and 28 showed a positive response; 18 had a vasodepressor response (systolic blood pressure dropped > or = 50% without a decrease in heart rate) and 10 had a vasovagal response (systolic blood pressure dropped > or = 50% with a decrease in heart rate of > or = 30%). The mean RR-interval, the standard deviation of normal sinus RR-intervals (standard deviation of RR-interval) and power spectra were measured in consecutive 2 min periods throughout the study. Power spectra consisted of low frequency (0.04-0.15 Hz), high frequency (0.15-0.40 Hz) and total spectra (0.01-1.0 Hz). Both high frequency spectra and the low/high frequency spectra ratio significantly changed with head-up tilt testing regardless of the response. However, high frequency, low frequency and total spectra increased in relation to symptoms. These changes were most profound in the high frequency spectra of subjects with a vasovagal response. Since high frequency spectra reflect parasympathetic tone, a profound change in the high frequency spectra implies that parasympathetic activities play a significant role in patients with a vasovagal response. The assessment of heart rate variability during head-up tilt testing can provide new insight into the pathogenesis of syncope of undetermined etiology.

Randomized, double-blind comparison of intravenous amiodarone and bretylium in the treatment of patients with recurrent, hemodynamically destabilizing ventricular tachycardia or fibrillation. The Intravenous Amiodarone Multicenter Investigators Group.

BACKGROUND: After several days of loading, oral amiodarone, a class III antiarrhythmic, is highly effective in controlling ventricular tachyarrhythmias; however, the delay in onset of activity is not acceptable in patients with immediately life-threatening arrhythmias. Therefore, an intravenous form of therapy is advantageous. This study was designed to compare the safety and efficacy of a high and a low dose of intravenous amiodarone with bretylium, the only approved class III antiarrhythmic agent. METHODS AND RESULTS: A total of 302 patients with refractory, hemodynamically destabilizing ventricular tachycardia or ventricular fibrillation were enrolled in this double-blind trial at 82 medical centers in the United States. They were randomly assigned to therapy with intravenous bretylium (4.7 g) or intravenous amiodarone administered in a high dose (1.8 g) or a low dose (0.2 g). The primary analysis, arrhythmia event rate during the first 48 hours of therapy, showed comparable efficacy between the bretylium group and the high-dose (1000 mg/24 h) amiodarone group that was greater than that of the low-dose (125 mg/24 h) amiodarone group. Similar results were obtained in the secondary analyses of time to first event and the proportion of patients requiring supplemental infusions. Overall mortality in the 48-hour double-blind period was 13.6% and was not significantly different among the three treatment groups. Significantly more patients treated with bretylium had hypotension compared with the two amiodarone groups. More patients remained on the 1000-mg amiodarone regimen than on the other regimens. CONCLUSIONS: Bretylium and amiodarone appear to have comparable efficacies for the treatment of highly malignant ventricular arrhythmias. Bretylium use, however, may be limited by a high incidence of hypotension.

Power law analysis of the signal-averaged electrocardiogram for identification of patients with ventricular tachycardia: effect of bundle branch block.

Signal-averaged ECGs that use time-domain analysis are useful for the identification of patients at risk for ventricular tachycardia (VT). Bundle branch block (BBB) and other conduction defects reduce the value of this approach, but frequency-domain analysis has shown promise in such patients. The purpose of the present study was to examine a new frequency-domain approach to signal-averaged ECGs in patients with and without BBB: power law scaling (PLS). PLS was performed by plotting the power spectrum of the entire signal-averaged ECG on a plot of log power versus log frequency and determining the slope (beta) by least-squares regression. This method was studied in 346 patients. Results of discriminant analysis revealed better sensitivity, specificity, positive predictive value, negative predictive value, and percentage correctly predicted when this method was compared with time-domain indexes. A large proportion of the variance in PLS (19%) was found to be due to findings in patients with VT; whereas the best time-domain index, duration of the filtered QRS signal, explained only 6% of the variance in the group with VT. Mean levels of PLS (+/- standard deviation) were decreased for the group with VT (-3.55 +/- 0.95) as compared with the group without VT (-4.34 +/- 0.59; p < 0.001), suggesting a decrease in the time correlation of the signal. Thus this method of frequency-domain analysis of the signal-averaged ECG was useful in identifying patients with sustained VT despite the presence of significant conduction defects.(ABSTRACT TRUNCATED AT 250 WORDS)

In anterior myocardial infarction, frequency domain is better than time domain analysis of the signal-averaged ECG for identifying patients at risk for sustained ventricular tachycardia.

Low amplitude signals at the end of the QRS in patients with prior myocardial infarction (MI) are related to fragmentation of the electrical impulse in ventricular myocardium and are known to correlate with an increased risk of sustained ventricular tachycardia (VT). We hypothesized that in patients with anterior MI (AMI), earlier activation of the damaged anterior wall would cause an earlier fragmentation of the signal-averaged ECG (SAECG) signal, making conventional time domain analysis of late potentials difficult. We performed SAECG in 213 patients (62 with AMI and 58 with inferior MI [IMI]). Fifty-seven had prior sustained VT; 23 with AMI and 24 with IMI. We examined the standard time domain SAECG parameters including the duration of the filtered QRS (40-250 Hz), the duration of the late QRS < 40 microV, and the root mean square amplitude of the last 40 msec of the QRS. We also examined the power law scaling (PLS) in the frequency domain. Receiver operating characteristic curve analysis of a discriminant function demonstrated significant differences for PLS as compared to time domain indices. An important finding was the significance of MI locus in the time domain indices. PLS did not exhibit this dependence. These data suggest that the usual indices are insufficient for identifying AMI patients at risk of VT. PLS, on the other hand, is valuable regardless of MI location.

Unusual Wenckebach upper rate response of an atrial-based DDD pacemaker.

We describe in this report an unusual form of Wenckebach upper rate response produced by a DDD pulse generator with atrial-based lower rate timing. The pacemaker maintained the programmed upper and lower rate intervals at the expense of a prolonged atrial paced-ventricular paced AV interval. This form of upper rate behavior eliminated the longer cycle (containing the unsensed P wave) that occurs at the end of the pacemaker Wenckebach sequence during traditional DDD pacing with ventricular-based lower rate timing.

Pacemaker hemodynamics: clinical implications.

Our review of the current literature and experience in caring for pacemaker patients suggests that a consideration of hemodynamics is a logical way to approach pacemaker selection and programming. Multiple clinical factors enter into the selection of a pacemaker or pacemaker programming settings in each case. It appears that in patients with sinus node disease, atrial-inhibited or dual-chamber pacing provides the best chance for preventing the development of chronic atrial fibrillation with its attendant risks of embolism and stroke. It is clear that AV synchrony has beneficial hemodynamic effects at rest in most patients. The results of Labovitz would suggest that in patients with marked left atrial enlargement, this may be less so. The results of Stewart et al would further suggest that in patients with retrograde VA conduction, dual-chamber pacing is preferable. Retrograde VA conduction can be intermittent and this makes it difficult to use its absence on a single test to decide on the type of pacemaker to use. It appears that baseline left ventricular function does not determine the relative improvement in cardiac output observed with AV synchrony or rate-adaptive pacing. However, in patients with severe congestive heart failure even a small improvement in cardiac output may result in significant clinical improvement. Studies have shown that in any given patient, there may be an optimal AV interval at rest. In general, this ranges from 100 to 150 milliseconds. In normal individuals the optimal AV interval shortens with increased heart rate during exercise in a predictable and linear fashion. The hemodynamic benefits of a shortened AV interval with faster heart rates in pacemaker patients have not yet been shown. Intuitively, however, this would appear to be a desirable approach and will probably be added to the design of future generations of dual-chamber pacemakers. Studies of the effect of different pacing modes on secretion of atrial natriuretic factor are intriguing and may contribute more to our understanding of pacing hemodynamics in the future. During exercise, heart rate increase is more important than AV synchrony and this has been shown by several studies. Thus, in active patients with chronotropic incompetence due to sick sinus syndrome, the addition of rate-adaptive pacing is important. Because single-chamber rate-adaptive atrial pacing leaves the patient exposed to the risk of future development of AV block and DDD pacing does not provide chronotropic support, it is likely that the new rate-adaptive dual-chamber (DDDR) devices will be used in a significant number of these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic and antiarrhythmic effects of magnesium in patients with inducible ventricular tachyarrhythmia.

Intravenous magnesium is reported to be effective in the treatment of ventricular arrhythmias associated with hypomagnesemia, digitalis toxicity, or prolongation of the QT interval. In most previous reports, magnesium was added to conventional antiarrhythmic drugs that had failed. There are few data on the antiarrhythmic efficacy of magnesium as monotherapy in patients without these associated abnormalities. Ten patients with life-threatening ventricular arrhythmia and inducible ventricular tachyarrhythmia by programmed electrophysiologic testing were treated with intravenous magnesium. Following magnesium infusion, all patients still had inducible ventricular tachyarrhythmia. Moreover, magnesium therapy was not associated with significant changes in ventricular refractory period or in the morphology, cycle length, or hemodynamic response to induced ventricular tachycardia. These data suggest that intravenous magnesium has no significant electrophysiologic or antiarrhythmic effects in patients with life-threatening ventricular arrhythmia and inducible ventricular tachyarrhythmia.

Importance of myocardial infarct artery patency on the prevalence of ventricular arrhythmia and late potentials after thrombolysis in acute myocardial infarction.

Sustained infarct artery patency is an important determinant of survival in patients with acute myocardial infarction. We studied 61 patients with acute myocardial infarction who received intravenous recombinant tissue-type plasminogen activator, aspirin or heparin within 6 hours of symptom onset, to determine if infarct artery patency after intravenous thrombolytic therapy influences myocardial electrical stability as measured by the prevalence of spontaneous ventricular ectopy or late potential activity. Infarct artery patency was determined by angiographic evaluation 2.5 +/- 3 days after infarction. Forty-eight patients (79%) had a patent infarct-related artery and 13 (21%) patients had an occluded vessel. The mean number of ventricular premature complexes (VPCs)/hour (p less than 0.01) and the prevalence of late potentials (54 vs 19%; p less than 0.03) were significantly higher in patients with an occluded versus patent-infarct related vessel. Although VPC frequency and late potentials were not influenced by the time to thrombolytic treatment, patients with a patent infarct-related artery had a lower prevalence of late potentials regardless of whether treatment was initiated less than or equal to 2 hours (25% patent vs 50% occluded; p = not significant) or 2 to 6 hours (16% patent vs 55% occluded; p greater than 0.03) after symptom onset. Thus, successful thrombolysis decreases the frequency of ventricular ectopic activity and late potentials in the early postinfarction phase. The reduction in both markers of electrical instability may help explain why the prognosis after successful thrombolysis is improved after acute myocardial infarction.

Atrial pacing with two-dimensional echocardiography for evaluation of chest pain: comparison with thallium 201 scintigraphy.

Atrial pacing was performed with two-dimensional (2-D) echocardiography and thallium 201 scintigraphy in 40 men with stable chest pain. Coronary angiography showed significant (one or more lesions greater than or equal to 50%) coronary artery disease (CAD) in 36 patients and no or insignificant CAD in 4. Two dimensional echocardiography showed a left ventricular wall motion abnormality (WMA) either at rest or with pacing in 28 (78%) patients with CAD, with 17 (47%) showing a new or worsened WMA with pacing. A thallium scan showing abnormality (reversible or fixed perfusion defect) was seen in 26 (72%) patients with CAD; 18 (50%) had a reversible defect. In all, 34 of the 36 patients with CAD (94%) had a WMA, a perfusion defect, or both (specificity 50%). Occurrence of both a WMA and a perfusion defect in individual segments ranged from 10 of 25 patients with septal abnormalities to 0 of 12 with abnormalities of the lateral segment. Sensitivity of 2-D echocardiography for identifying CAD in specific vessels was 81% for the left anterior descending (LAD) artery, 30% for the right coronary artery, and 20% for the circumflex artery (both p less than .001 compared with the LAD artery). Corresponding sensitivities for thallium 201 imaging were 54% (p less than .05 compared with 2-D echocardiography), 27%, and 8% (both p less than .05 compared with the LAD artery). When combined with atrial pacing, 2-D echocardiography and thallium 201 perfusion imaging are of similar value for diagnosing the presence of CAD in patients with stable chest pain. Two-dimensional echocardiography is superior to thallium 201 imaging for identifying the presence of significant CAD in the LAD artery, but both tests are limited in their ability to detect lesions of the right coronary or circumflex arteries.

Heart disease in systemic sclerosis.

Primary cardiovascular manifestations of SSc include pericardial disease, myocardial disease, conduction abnormalities, and cardiac arrhythmias. Significant cardiac abnormalities are present in more than half of SSc patients at autopsy. As the frequency of subclinical cardiac involvement is now appreciated and noninvasive cardiac diagnostic modalities continue to improve, the ability to detect early asymptomatic involvement in SSc has improved. Two-dimensional echocardiography, radionucleotide imaging, and ambulatory ECG allow recurrent serial testing with virtually no morbidity. The current treatment of cardiac involvement in SSc is emperic and primarily directed at symptomatology. Large prospective randomized trials are needed to determine if preventive therapy is effective. With the advent of new immunological and cardiotropic agents and a better understanding of the primary disease process, our ability to alter the pathogenesis and final outcome of cardiac involvement in SSc should improve.

Natural history of potentially lethal ventricular arrhythmias in patients treated with long-term antiarrhythmic drug therapy.

To examine the natural history of long-term anti-arrhythmic therapy in patients with benign and potentially lethal ventricular premature complexes (VPCs), 28 patients with initial efficacy with moricizine (greater than 75% suppression of baseline mean VPCs/hr and greater than 90% suppression of repetitive VPCs) were prospectively followed for 1 to 56 (mean +/- standard deviation 25 +/- 17) months. Patients were examined during baseline placebo, anti-arrhythmic drug therapy and intermittent pulsed-placebo reexamination periods. The mean VPCs of all patients at baseline entry were 233 +/- 47 VPCs/hr, and after moricizine therapy 14 +/- 4 VPCs/hr. Follow-up demonstrated that antiarrhythmic efficacy decreased to 75% at 12 months and to 62% at 24 months. Loss of antiarrhythmic drug efficacy most commonly occurred as a "transient" event (10 patients [36%]), and efficacy was spontaneously reestablished without a change in antiarrhythmic therapy. In contrast, increased dose titration of moricizine was necessary to reestablish antiarrhythmic suppression efficacy in 4 patients (14%), and 4 patients (14%) lost antiarrhythmic drug responsiveness during follow-up. Spontaneous decrease in baseline VPCs resulted in discontinuation of antiarrhythmic therapy in 3 patients, and increase in baseline VPCs was associated with a loss of antiarrhythmic response in 2 patients. Late proarrhythmic effects (2 patients, 7%), delayed side effects necessitating drug withdrawal (6 patients, 21%) and medical events (4 patients, 14%) occurred during 56 months of follow-up. Individual serum moricizine levels remained in the therapeutic range throughout the study and did not correlate with changes in antiarrhythmic efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)

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)