The autonomic and hemodynamic effects of oral theophylline in patients with vasodepressor syncope.

Adenosine appears to be an important mediator of hypotension and bradycardia in certain subsets of patients with vasodepressor syncope. Adenosine receptor blockage with methylxanthines may hypothetically prevent the vasodepressor spell. We studied the chronotropic, hemodynamic, and cardiac autonomic responses to head-up tilt in patients (mean age 40.7 +/- 18.1 years) with vasodepressor syncope before and after treatment with oral theophylline. At baseline, hypotension and syncope or near syncope were induced at 11.7 +/- 2.3 minutes of 60 degrees head-up tilt in all patients. Cardiac vagal and sympathetic tone showed biphasic and directionally opposite changes during tilt. Repeat tilt during oral theophylline therapy (6-12 mg/kg/day for 14 +/- 6 days) did not provoke symptomatic hypotension in 82% of patients. During 10.7 +/- 6.1 months of follow-up, seven patients had no recurrence of vasodepressor syncope and seven patients discontinued theophylline because of adverse reactions. Low-dose theophylline prevents tilt-induced vasodepressor syncope and may prevent spontaneous vasodepressor syncope in selected patients who can tolerate theophylline.

Adrenergic hyperactivity and cardiac abnormality in primary disorders of sleep.

Symptoms suggesting autonomic instability and increased adrenergic effect were identified in 53 patients with primary disorders of impaired wakefulness. Urine and plasma catecholamine concentrations were significantly increased in patients with sleep apnea. Excessive increases in heart rate during isoproterenol infusions suggested adrenergic hyperresponsiveness as an alternative explanation for symptoms of catecholamine excess in some individuals. Twenty-two patients demonstrated mitral valve prolapse (MVP), implicating primary neurologic disturbances as potential factors in the fatigue and lassitude often associated with MVP. The catecholamine abnormalities may explain some of the difficulties frequently encountered in using stimulants to treat sleep disorders.

Sleep apnea: treatment with protriptyline.

Fourteen patients with an average of more than 60 episodes of upper airway obstruction during night sleep were treated with a nonsedating tricyclic antidepressant, protriptyline. Frequency and duration of recorded apneas decreased in 11 cases, and satisfactory control of sleep apnea was maintained with medical therapy alone in 8 of these 11 patients for 7 to 15 months. Potential adverse effects of protriptyline, particularly on the cardiovascular system, limit its use in this illness. These results indicate the possibility of pharmacologic reversal of sleep-induced incoordination of the upper airway.

Electrophysiologic studies of perphenazine and protriptyline in a patient with psychotropic drug-induced ventricular fibrillation.

A 51 year old woman sustained ventricular fibrillation while receiving perphenazine and protriptyline. After successful resuscitation and clinical stabilization, cardiac electrophysiologic studies were performed before and after the administration of each of these medications. Perphenazine widened the ventricular echo zone and facilitated induction of short salvoes of ventricular tachycardia (repetitive ventricular response). Protriptyline also widened the ventricular echo zone and allowed easy induction of long runs of ventricular tachycardia. Both psychotropic agents increased the incidence of ventricular dysrhythmias in this patient. The electrophysiologic study is a useful technique in determining the interaction between psychotropic drugs and life-threatening arrhythmias; it may provide a means of identifying the patients with cardiac disease in whom administration of these agents may be fatal.

Electrophysiologic mechanisms of provoked atrial flutter in mitral valve prolapse syndrome.

To examine the electrophysiologic determinants of provoked atrial flutter (AF) in patients with mitral valve prolapse (MVP), studies were performed in 4 groups of patients: group 1 (n = 5), patients with MVP and AF; group 2 (n = 6), patients without MVP but with AF; group 3 (n = 6), patients with MVP but without AF; and group 4 (n = 5), patients without MVP and without AF. P-wave duration, intraatrial conduction, interatrial conduction and effective refractory periods for both the high right atrium and the low right atrium were longer in group 2 than in group 1. The effective refractory period of the low right atrium was longer in group 3 than in group 1. The interatrial conduction interval was longer in group 2 than in group 4. Thus, in patients without MVP, atrial conduction delay is the predominant determinant of AF, whereas differences in right atrial refractoriness appear to be most important to the provocation of AF in the patient with MVP. These differences in atrial refractoriness may be a result of abnormal autonomic influences in patients with MVP.

Clinical significance of an equivocal signal-averaged electrocardiogram.

Patients with an equivocal signal averaged electrocardiogram (SAECG) had less heart disease and better prognosis than patients with overtly abnormal SAECGs. An equivocal SAECG should not prompt further invasive diagnostic testing for ventricular tachycardia unless other clinical risk factors are present.

Enhanced diagnostic power of exercise testing for myocardial ischemia by addition of postexercise left ventricular ejection time.

To improve both the sensitivity and specificity of the multistage treadmill test, postexercise systolic time intervals were prospectively studied in 73 patients with angina-like chest pain and normal resting ST-T segments. The decision to perform coronary angiography was made independent of the exercise test. Twenty-three patients had normal coronary arteries and 50 had more than 50 percent reduction of luminal diameter of one or more major coronary arteries. The systolic time intervals were measured before and 2,4,6,8 and 10 minutes after exercise. Of all the systolic time intervals, the 4 minute postexercise left ventricular ejection time proved most discriminating between normal subjects and those with coronary artery disease. The deviations of this interval from the normal regression with heart rate both before and after exercise were used to calculate the net delta left ventricular ejection time after exercise. A net increase of more than 31 msec represented 2 standard deviations above normal. Twenty-three (46 percent) of the patients with coronary artery disease had an abnormal net delta ejection time after exercise. Twenty-five (50 percent) had a positive electrocardiographic response with a 9 percent false positive rate. Thirteen (26 percent) had only a positive postexercise net delta ejection time so that a total of 76 percent of patients with coronary artery disease were identified. Thus, measurement of the postexercise net delta ejection time a simple and useful adjunct to multistage treadmill testing.

Interatrial conduction (activation) times.

Left atrial electrograms were recorded simultaneously from sites located in the coronary sinus, right pulmonary artery and esophagus in order to determine and correlate the interatrial conduction times obtained from these locations. Ten patients with normal-sized atria and 16 patients with isolated left atrial enlargement were studied. A high correlation existed between the P wave duration and the interatrial conduction times obtained from the coronary sinus and pulmonary artery; good correlations were also found for the interatrial conduction times recorded from the pulmonary artery and esophagus correlated well with those recorded from the distal coronary sinus (the generally accepted standard for the indirect interatrial conduction time measurements). In addition to providing information on the mechanism of atrial arrhythmias, the electrograms obtained from the various indirect left atrial recording sites provide satisfactory quantification of interatrial conduction.

Localization of the site of ventricular premature complexes by radionuclide angiographic phase imaging.

To investigate whether gated radionuclide angiographic phase imaging is useful for visually displaying the origin of ventricular premature complexes (VPCs), 82 patients were studied by gating only VPCs. The VPC "origin" by the scintigraphic method was defined as the area of earliest phase and was compared with that predicted by 12-lead electrocardiographic criteria in all patients and to invasive electrophysiologic mapping in 10. Separating the right ventricle into 3 and the left ventricle into 4 segments, the phase imaging method and the electrocardiographic criteria agreed as to ventricle of VPC origin in 69 patients (84%) and segment of origin within each ventricle in 46 (56%). When baseline ventricular wall motion was analyzed, the 2 methods agreed to the ventricle of VPC origin in 31 of 33 patients (94%) with normal wall motion, 20 of 23 (87%) with segmental wall motion abnormalities and 19 of 26 (73%) with diffuse wall motion abnormalities. Agreement between the 2 methods as to specific segmental localization of the arrhythmia focus was noted in 21 of 33 patients (64%) with normal wall motion, 11 of 23 (48%) with segmental wall motion abnormalities and 12 of 26 (46%) with diffuse hypocontractility. In the 10 patients with endocardial mapping studies, the phase imaging technique confirmed the segment of VPC origin in all 10; the electrocardiographic method was accurate in 8. Thus, gated radionuclide angiographic phase imaging methods may be of value in noninvasively defining the origin of spontaneous VPCs. The visual format allows ready interpretation of the arrhythmia origin, and there may be an advantage to this approach over electrocardiographic morphometric criteria.

Syncope.

Syncope is a clinical entity of diverse cause. The historical features surrounding the syncopal event and the presence or absence of heart disease are the most important features in establishing the cause for syncope. Passive head-up tilt study provides a means of identifying many patients with vasodepressor syncope. Electrophysiologic study is important in the elucidation of syncope in patients who have syncope undefined after noninvasive evaluation. With proper use of the modalities available, few patients will have an undefined cause for syncope.

Negative inotropic effect of lidocaine in patients with coronary arterial disease and normal subjects.

The effect of administration of lidocaine on left ventricular performance was studied using systolic time intervals in nine normal subjects, eight patients with stable angina, and 15 patients with acute myocardial infarction. The greatest response in systolic time intervals occurred at three minutes after intravenous injection of lidocaine (100 mg), with values returning to baseline at 10 to 15 minutes. Administration of lidocaine produced a significant prolongation of the preejection period (PEP) corrected for heart rate in all groups and a prolongation of the ratio of PEP to left ventricular ejection time (PEP/LVET) in patients with angina. The group with acute myocardial infarction exhibited a hyperadrenergic state, as shown by a short baseline QS2I. The QS I was lengthened by administration of lidocaine in all groups, but this was more profound in those with acute myocardial infarction. These changes in systolic time intervals were still present at two hours after injection in six patients with acute myocardial infarction in whom an infusion of lidocaine followed the initial bolus. The effect of administering lidocaine after intravenous injection of propranolol (5 mg) was also studied in six normal subjects. Although propranolol therapy along prolonged the PEP/LVET, a further significant prolongation followed subsequent injection of lidocaine.

Repolarization variant vs acute pericarditis. A prospective electrocardiographic and echocardiographic evaluation.

Patients with ECG nonischemic ST segment elevation were prospectively studied to determine the accuracy of the initial ECG diagnoses. Evaluations were made of 131 consecutive patients by serial clinical, ECG, and echocardiography to establish a diagnosis. Eighty-six (66 percent) had an initial ECG interpretation of repolarization variant. Only three of the 86 (3 percent) subsequently met clinical criteria for acute pericarditis. Analysis of the mean frontal ST segment vector and PR segment depression revealed no significant differences between the 119 patients with final clinical diagnosis of repolarization variant and the 12 with clinical acute pericarditis. The diagnostic reliability of the initial ECG alone as a means of confirming acute pericarditis is low (9/45, 20 percent) but in the detection of repolarization variant is extremely high (83/86, 97 percent).

Self-conversion of paroxysmal atrial tachycardia by radio-frequency-triggered pacemaker.

The case of a 73-year-old woman with frequent disabling attacks of supraventricular tachycardia refractory to pharmacological therapy is presented. Successful management was achieved with a radio-frequency-activated pacemaker.

Evaluation of an open-loop, computer-based infusion system designed to achieve a series of constant, targeted plasma procainamide concentrations in patients undergoing electrophysiologic testing.

STUDY OBJECTIVE: To evaluate the performance of a computer-based procainamide infusion system in patients undergoing electrophysiologic testing. DESIGN: Prospective case series. SETTING: Electrophysiology laboratory in a university hospital. PATIENTS: Thirty-four patients with inducible sustained ventricular tachycardia. INTERVENTIONS: Intravenous infusion of procainamide to achieve and maintain targeted plasma concentrations. MEASUREMENTS AND MAIN RESULTS: System performance was assessed by comparing targeted and observed plasma concentrations. The population median absolute performance error (size of typical miss) was 12.6% (95% CI 11.2-14.1%). The population median performance error (system bias) was not significantly different from zero. A small but statistically significant improvement in performance over time was observed (population absolute performance error divergence -0.125%/min). Population wobble (overall system stability) was 7.6% (95% CI 6.8-8.3%). Population-based estimates of central compartment volume and volume of distribution at steady state were significantly higher and lower, respectively, than estimates used by the infusion system. CONCLUSION: The computer-based infusion system is capable of achieving and maintaining a series of targeted procainamide concentrations in patients undergoing electrophysiologic testing.

Physiological adjustments to higher- or lower-intensity exercise in elders.

A program of physical activity for people over 60 yr of age was developed to determine whether exercising at lower intensities (LI) is a significant conditioning stimulus. In addition, differences in aerobic capacities (VO2max) elicited by training at LI, as opposed to training at higher intensities (HI), were evaluated. Thirty-two volunteers over 60 yr of age (mean = 67.8 yr) participated in a 9-wk exercise program. After initial testing of VO2max on a cycle ergometer, subjects were assigned randomly to the HI, LI, or control group. Endurance training of the two exercise groups on cycle ergometers was maintained at 30-45% (N = 14) or 60-75% (N = 14) of the range (HRR) between the subject's resting and maximum heart rate for 25 min during each exercise session. These training intensities represented 57 and 70% of the VO2max of the LI and HI groups, respectively. Participants averaged three exercise sessions per week. Non-exercising volunteers served as control subjects. A one-way ANOVA with repeated measures was utilized for comparisons of retest, groups, and interaction. As a result of the exercise program, significant changes (P less than 0.005) in absolute (VO2max, 1 X min-1) and relative (VO2max, ml X min-1 X kg-1) aerobic capacities were realized within each training group while initial and post-training VO2max were not significantly different between the two groups. Similar changes were documented by a reduction in heart rate at submaximal exercise intensities and during recovery. It was concluded that exercising at LI (30-45% HRR) is an adequate training stimulus in older individuals and produces changes in VO2max that are comparable to those elicited by HI (60-75% HRR) training.

Mitral valve prolapse: cardiac arrest with long-term survival.

Cardiac arrest has been reported in patients with mitral valve prolapse; however, clinical characteristics and survival information are limited since most of the cases reported include autopsy data. Nine patients (2 male, 7 female) with mitral valve prolapse were identified who had cardiac arrest; ventricular fibrillation was documented in 8 patients; resuscitation was unsuccessful in 2. Eight had a history of palpitations (months to 15 years duration) and ventricular arrhythmias, 3 had a history (5-15 years) of recurrent syncope, and 1 was totally asymptomatic. Cardiac catheterization-angiographic studies in 8 patients demonstrated normal coronary artery anatomy and mitral valve prolapse. All 9 patients had auscultatory and echocardiographic evidence of mitral valve prolapse. Seven survivors (6 still alive) were followed from 3 to 14 years after cardiac arrest. A subset of patients with mitral valve prolapse and cardiac arrest is described in whom past medical history is compatible with cardiac arrhythmias or syncope, and whose long-term prognosis appears better than patients with other causes of cardiac arrest.

Arrhythmic syncope: what to do when ambulatory monitoring is non-diagnostic.

The two new methods for defining arrhythmic syncope described in this report represent important additions to the traditional syncope workup. Both techniques uncovered a substantial number of arrhythmic causes of syncope which had not been found by standard techniques. A major strength of each method is that symptoms can be directly related to the arrhythmia. The 68% incidence of diagnostic EPS abnormalities which we found was identical to the study of DiMarco but higher than reported by others (which have ranged from 12 to 48%) (18, 20, 21). More critical patient selection and more comprehensive study techniques most likely account for these differences. It is our opinion that a significant number of patients whose diagnosis was "syncope of undetermined etiology" in previous studies did indeed have an arrhythmic basis for their symptoms which was not identified. At this point the issue of "cost effectiveness" inevitably arises. Do all patients with syncope in whom a cause is not initially apparent (i.e., up to 50% of such patients) require either TTEM or EPS? The answer is obviously no, not for this whole population. However, the evident power of TTEM and EPS requires that the question should be raised. Furthermore, the results of the invasive EPS study strongly suggest that mortality and morbidity can be reduced. Table 11 shows the relative costs for all of the diagnostic tests for arrhythmic syncope. From this it can be seen that TTEM is quite inexpensive and therefore very cost-effective. It is an ideal adjunct to 24 hour ambulatory monitoring in selected patients. Although invasive EPS studies are costly, it is not difficult to incur equal costs by use of several days of prolonged monitoring, especially if done in the hospital. Thus, in identified patients with abnormal but "not diagnostic" ambulatory monitoring studies, patients with abrupt syncope, patients with frequent symptoms or patients with known underlying heart disease, further evaluation with TTEM or EPS should be strongly considered.