Perspectives and future trends in cellular electrophysiology: implications for the clinician.

As a result of single fiber electrophysiologic studies, the clinical approach to the electrical behavior of the heart has improved. Three areas are examined: 1) the electrocardiographic waveform, 2) normal and abnormal cardiac rhythms, and 3) the mechanism of action of antiarrhythmic drugs. In each area, the results of single fiber studies have provided a conceptual framework for diagnostic and therapeutic decisions. These studies have also enabled investigators to test hypotheses formulated from clinical observations. It may be only a slight exaggeration to attribute many of our recent advances in each of the three areas to the development and use of the microelectrode.

Lack of specificity of new negative U waves for anterior myocardial ischemia as evidenced by intracoronary electrogram during balloon angioplasty.

Negative U waves on the surface electrocardiogram are reported to be a specific marker of myocardial disease. In the setting of ischemia, they correlate with stenosis of the left main and left anterior descending coronary arteries. To determine whether U wave changes are unique for anterior ischemia, the development of new U waves on the intracoronary electrogram was correlated with the location and magnitude of ischemia during coronary balloon angioplasty. Recordings were obtained during dilation of 43 vessels in 37 patients. New negative U waves developed during dilation of 12 vessels (7 of the left anterior descending, 4 of the left circumflex and 1 of the right coronary artery). New positive U waves developed during dilation of 18 vessels (12 of the left anterior descending, 3 of the left circumflex and 3 of the right coronary artery). The magnitude of ST segment change was 10.9 +/- 6.7 mm in the presence of a new U wave but only 3.4 +/- 2.8 mm in the absence of a new U wave (p less than 0.001). It is concluded that 1) negative U waves on the intracoronary electrogram are not specific for anterior ischemia; 2) new positive U waves on the intracoronary electrogram are as sensitive as new negative U waves for acute ischemia; 3) the development of a new positive or negative U wave is associated with the magnitude of myocardial ischemia; and 4) the recording of U waves may be related to the proximity of the recording leads to the location of ischemia.

Exercise-induced distal atrioventricular block.

Three patients with 1:1 atrioventricular (AV) conduction at rest developed fixed 2:1 or 3:1 AV block during treadmill exercise testing. Electrophysiologic study documented block distal to the AV node in all three patients, and suggested that the exercise-induced block occurred because of increased atrial rate and abnormal refractoriness of the His-Purkinje conduction system. The findings in these three patients suggest that high grade AV block appearing during exercise reflects conduction disease of the His-Purkinje system rather than of the AV node, even in the absence of bundle branch block. Patients with this diagnosis should be considered for permanent cardiac pacing.

Identification of false positive exercise tests with use of electrocardiographic criteria: a possible role for atrial repolarization waves.

Atrial repolarization waves are opposite in direction to P waves, may have a magnitude of 100 to 200 mu V and may extend into the ST segment and T wave. It was postulated that exaggerated atrial repolarization waves during exercise could produce ST segment depression mimicking myocardial ischemia. The P waves, PR segments and ST segments were studied in leads II, III, aVF and V4 to V6 in 69 patients whose exercise electrocardiogram (ECG) suggested ischemia (100 mu V horizontal or 150 mu V upsloping ST depression 80 ms after the J point). All had a normal ECG at rest. The exercise test in 25 patients (52% male, mean age 53 years) was deemed false positive because of normal coronary arteriograms and left ventricular function (5 patients) or normal stress single photon emission computed tomographic thallium or gated blood pool scans (16 patients), or both (4 patients). Forty-four patients with a similar age and gender distribution, anginal chest pain and at least one coronary stenosis greater than or equal to 80% served as a true positive control group. The false positive group was characterized by 1) markedly downsloping PR segments at peak exercise, 2) longer exercise time and more rapid peak exercise heart rate than those of the true positive group, and 3) absence of exercise-induced chest pain. The false positive group also displayed significantly greater absolute P wave amplitudes at peak exercise and greater augmentation of P wave amplitude by exercise in all six ECG leads than were observed in the true positive group.(ABSTRACT TRUNCATED AT 250 WORDS)

Nonemergent cardiac catheterization and risk-stratified revascularization following thrombolytic therapy for acute myocardial infarction. A critical analysis of therapy in the community setting. University of North Carolina Cardiology Consortium.

We evaluated a strategy for administering thrombolytic therapy without emergent cardiac catheterization to patients with acute myocardial infarction in community hospitals. Fifty-nine patients were treated with intravenous streptokinase and heparin, and referred for elective catheterization. Angioplasty or bypass surgery was performed only in patients judged to be at risk for reinfarction. One or more predetermined criteria for infarct segment viability were present in 47 (80%) of 59 patients. Angina recurred in 24 patients and enzyme-positive reinfarction in 9 patients, but only 2 patients developed new Q waves or a creatine kinase rise to over twice the normal value. Of 18 patients judged to be at low risk for reinfarction, only 1 required urgent angioplasty or bypass surgery. Fourteen-day mortality was 7% and infarct vessel patency was 94%. These data indicate that physicians in small community hospitals with a close relationship to a referral center and with a carefully designed protocol can administer thrombolytic therapy safely and effectively. By subsequent stratification of patients according to the risk of recurrent infarction, 22% of patients eligible for revascularization were spared urgent angioplasty or bypass surgery.

Effects of bretylium and lidocaine on ventricular fibrillation in the isolated rabbit heart.

We studied the effects of bretylium tosylate and lidocaine on ventricular fibrillation in the isolated, perfused rabbit heart induced by perfusion with potassium-deficient solutions and by premature stimuli. The purpose of the study was to determine if the reported antifibrillatory effects of the drugs could be reproduced in the absence of an intact sympathetic nervous system. Lidocaine in the concentration of 5 mug/ml. prevented ventricular fibrillation induced by both methods while bretylium, in concentrations of 25 to 50 mug/ml. prevented neither type of filbrillation. These results indicate that the antifibrillatory effects of lidocaine can be attributed to drug-induced alterations in cellular electrophysiology, whereas those of bretylium are independent of such changes. Our study suggests that the reported antifibrillatory capability of bretylium is related to the drug's effects at sympathetic nerve terminals and thus is dependent upon an intact sympathetic nervous system.

Reproducibility and treatment of exercise-induced ventricular tachycardia.

Fourteen patients with exercise-induced ventricular tachycardia (VT) underwent serial treadmill testing, and those with reproducible arrhythmia were treated with a beta-adrenergic blocking agent. In 11 patients (79%), VT of similar rate, morphologic characteristics and duration was reproduced on 2 consecutive treadmill tests performed 1 to 14 days apart. Beta blockade prevented recurrent VT during acute testing in 10 of 11 patients and during chronic therapy in 9. Eight patients had a consistent relation between a critical sinus rate and the onset of VT. In these patients, successful therapy correlated with preventing achievement of the critical sinus rate during maximal exercise. Thus, serial exercise testing is an appropriate means of assessing efficacy of therapy in patients with exercise-induced VT, provided that reproducibility is established on 2 control tests before beginning treatment. Therapy with beta-blocking agents is effective, especially when guided by the presence of a critical sinus rate-VT relation.

Atrial excitability and conduction in patients with interatrial conduction defects.

Prolongation of P-wave duration is an accepted indicator of an interatrial conduction disturbance and may predispose patients to atrial arrhythmias. This study was performed to monitor electrophysiologic characteristics of the atria in patients with a prolonged P-wave duration. Atrial excitability and conduction times were compared in 7 patients with a P-wave duration of less than 115 ms (Group I), and 13 patients with a duration of greater than of equal to 115 ms (Group II). In contrast of the Group I patients, most of the 13 patients in Group II had atrial arrhythmias, including sinus nodal dysfunction (3 patients) and a history of atrial fibrillation or ectopic atrial tachycardia (6 patients). Electrophysiologic differences between the 2 groups included a higher late diastolic threshold in Group II (0.8 +/- 0.2 mA versus 1.3 +/- 0.2 mA; p less than 0.005), and a greater increase in intraatrial conduction time (5 +/- 10 ms versus 30 +/- 20 ms; p less than 0.005) and interatrial conduction time (5 +/- 15 ms versus 30 +/- 15 ms; p less than 0.05) of early premature responses. There were no differences between the 2 groups in refractory periods, shape of the strength interval curve, or conduction times of premature responses occurring late in diastole. These abnormalities in conduction time and excitability found in patients with a prolonged P-wave duration may predispose to the initiation of certain atrial tachyarrhythmias.

Multiformity if induced unifocal ventricular premature beats in human subjects: electrocardiographic and angiographic correlations.

Single ventricular premature responses induced by strength-interval pacing were elicited at multiple sites in 30 patients undergoing cardiac catheterization to determine if and under what circumstances unequivocally unifocal stimulated ventricular premature beats could manifest multiformity of the QRS configuration. Multiformity was defined as unifocal responses whose mean frontal axes differed by greater than 15 degrees with or without associated morphologic differences in the horizontal leads. Multiformity occurred in 12 (40 percent) of 30 patients. A statistically significant association was found between multiformity and the presence of a quantitatively defined left ventricle wall motion abnormally (p less than 0.01), prior myocardial infarction (p less than 0.01) and a left ventricular election fraction of less than 0.60 (p less than 0.05). Twelve (67 percent) of the 18 patients without multiformity had coronary artery disease, but only 4 of those 12 had a left ventricular wall motion abnormally or prior myocardial infarction, or both. Multiformity was also dependent on the site of stimulation and on the degree of prematurity. The results of this study indicate that the QRS configuration of early premature beats cannot be relied on as a predictor of their site of origin and multiformity is not necessarily synonymous with multifocality.

Efficacy of verapamil in exercise-induced ventricular tachycardia.

The antiarrhythmic efficacy of verapamil was determined by serial treadmill testing in 16 patients with reproducible exercise-induced ventricular tachycardia (VT). Twelve of the 16 patients responded to verapamil, 0.2 mg/kg intravenously; in 8 of these 12 responders, an oral verapamil regimen of 160 to 320 mg given every 8 hours also prevented exercise-induced VT. Plasma verapamil concentration was significantly higher in the responders than in the nonresponders to intravenous verapamil, but levels were similar in responders and nonresponders to oral therapy. The 8 responders to the oral drug were followed up while receiving verapamil therapy for 6 to 22 months (mean 15), and exercise-induced VT did not recur in any patient. Five of the 8 responders also had concomitant spontaneous VT unrelated to exercise which verapamil suppressed initially as well: 4 remained free of spontaneous VT, while 1 patient had recurrence of spontaneous VT. Thus, in patients with exercise-induced VT, verapamil is a promising alternative therapy to beta-adrenergic blocking agents. The effectiveness of verapamil is consistent with a mechanism of arrhythmogenesis involving calcium channels.

Use dependence of amiodarone during the sinus tachycardia of exercise in coronary artery disease.

The QRS duration at rest and during exercise was studied in 19 patients with coronary artery disease before and after oral amiodarone therapy to determine if this drug produces detectable rate-dependent conduction slowing during physiologic increases in heart rate. QRS duration did not change significantly during exercise in the absence of the drug. However, after amiodarone, QRS duration at rest increased from 99 to 114 ms (p less than 0.001), and increased further from 114 to 127 ms (p less than 0.001) during the 45 beats/min mean increase in heart rate produced by exercise. The magnitude of this effect was related to the resting QRS duration. After amiodarone therapy, the QRS increased during exercise by only 6% in 8 patients with QRS less than 110 ms, while in 12 patients with QRS greater than or equal to 110 ms, the QRS increased by 15% (p less than 0.05). Rate-dependent conduction slowing occurs during the sinus tachycardia of exercise in patients treated with amiodarone, presumbably due to use-dependent sodium channel blockade. This result is most pronounced in patients with abnormal ventricular conduction at rest.

Drug effects on the electrocardiogram. A review of their clinical importance.

It is clear that many patients are now being treated with multiple pharmacological agents which may alter membrane function and ionic fluxes across membranes. Therefore, these agents will frequently influence the electrical behavioural of all excitable tissues including the myocardial cell. The changes in the myocardial cell are often reflected by changes, some subtle, some obvious, on the body surface electrocardiogram. Thus, the electrocardiogram provides the physician with a reasonably simple and inexpensive tool for monitoring drug effects and for detecting changes that may be toxic and/or life-threatening. For this reason, an appreciation of these changes by the noncardiologist has become increasingly important.

Local myocardial biochemical and ionic alterations during myocardial ischaemia and reperfusion.

Acute myocardial ischaemia and reperfusion result in a series of inhomogeneous metabolic, ionic and neurohumoral events that explain the associated mechanical and electrical events, including cardiac death. The time course of the hydrolysis of high energy phosphates, the rise in extracellular potassium and the fall in intracellular and extracellular pH induced by acute no-flow ischaemia have been well characterised. However, the time course of the changes in intracellular sodium, calcium and magnesium levels is less clear. It appears that the changes in intracellular calcium may be pivotal to many of the biochemical and electrophysiological changes produced by the abrupt cessation of coronary arterial inflow and the associated interruption of venous washout. Consequently, agents that modify the handling of calcium by the sarcolemma and the sarcoplasmic reticulum have a significant impact on many of the metabolic, ionic and electrical abnormalities characterising acute ischaemia and reperfusion.

Painless ST-segment depression in patients with angina pectoris. Correlation with daily activities and cigarette smoking.

Ambulatory electrocardiographic monitoring was employed in 33 patients with angina pectoris and abnormal stress tests to determine the frequency with which myocardial ischemia manifested by painless ST-segment depression occurred during normal activity. ST-segment depression occurred in 24 patients during the monitoring period; and in 21, it occurred either solely in the absence of pain or both with and without pain. Of 109 recorded episodes of ST-segment depression, 61 percent were painless. The frequency of painless ST-segment depression was independent of activity other than automobile driving, during which all episodes were painless. In patients who smoked cigarettes, ST-segment depression was more common while smoking, but the incidence of painless ST-segment depression was not altered. The study indicates that ST-segment depression occurs more commonly in the absence than in the presence of chest pain and that ambulatory electrocardiographic monitoring is a useful method of determining the frequency of myocardial ischemia during normal daily activity.