Effects of carbon monoxide exposure in patients with documented cardiac arrhythmias.

OBJECTIVE: This study was designed to determine whether carbon monoxide has proarrhythmic effects at rest and during upright exercise in patients with myocardial ischemia and moderate baseline ectopic activity. BACKGROUND: Exposure of patients with documented myocardial ischemia to low levels of carboxyhemoglobin (COHb) alters the myocardial response to exercise. Anecdotal reports from patients with myocardial ischemia have noted the development of arrhythmias related to carbon monoxide exposure. Increased frequency of arrhythmias related to carbon monoxide exposure in patients performing supine bicycle exercise has been recently reported. METHODS: Twenty-eight nonsmoking men and five nonsmoking women with documented coronary artery disease and a minimum of 30 ventricular ectopic beats/h over a 20-h period were studied. Subjects were exposed in a randomized double-blind fashion to either room air or sufficient carbon monoxide to elevate their COHb concentration to 3% or 5% in 1 h, followed by a maintenance exposure to carbon monoxide. The subjects then left the laboratory and resumed their normal daily activity to determine changes in ventricular ectopic beats after carbon monoxide exposure. RESULTS: There was no significant change in the frequency of single ventricular ectopic beats at rest from 115 +/- 28 (in room air) to 121 +/- 31 at 3% COHb to 94 +/- 23 at 5% COHb. Exercise itself increased the frequency of ventricular ectopic beats, but there was no additional effect of carbon monoxide exposure on the exercise-induced increase in isolated ectopic beats or complex ectopic waveforms. Analysis of the data based on grouping of the subjects by the severity of disease (ventricular ectopic beat frequency, ejection fraction, presence of exercise-induced ischemia) indicated no proarrhythmic effect of carbon monoxide. CONCLUSIONS: In patients with frequent ventricular ectopic activity (> or = 30 ectopic beats/h), exposure to carbon monoxide producing either 3% or 5% COHb does not increase arrhythmia frequency of single or multiple beats during rest or exercise.

Left-axis deviation and adiposity: the United States Health and Nutrition Examination Survey.

The influence of body fatness on the direction of the electrocardiographic mean frontal plane QRS axis was investigated in a nationally representative population of 6,913 adults aged 25 to 74 years (the U.S. Health and Nutrition Examination Survey). Adiposity was measured as skinfold thickness and the mean frontal QRS axis was determined by computer analysis of limb lead vectors. A significant leftward shift of the mean QRS axis occurred with increasing fatness in both men and women (p less than 0.001) and was independent of age and blood pressure. However, this association was confined to the range of normal QRS axis. The prevalence of left-axis deviation (LAD) (QRS axis of -30 degrees or less) was not higher among those with greater measures of body fatness. There were no significant differences in mean age-adjusted skinfold thickness, height, weight or chest circumference between those with LAD and those with a normal QRS axis. Thus, although the direction of the mean frontal QRS axis is influenced significantly by body fatness throughout the normal QRS axis range, this association is lost as the QRS axis becomes abnormally deviated to the left. An ECG demonstrating LAD obtained from an obese person probably represents a true abnormality and not merely a reflection of adiposity.

Chronotropic incompetence in clinical exercise testing.

Chronotropic incompetence has been found to be an important predictor of obstructive coronary artery disease (CAD). However, few data define the normal heart rate response to progressive exercise and allow a clear definition of chronotropic incompetence. In this study, 312 patients who underwent an exercise stress test and coronary angiography were evaluated. The exercise heart rates of 140 normal subjects were used to define the normal mean heart rate at progressive work loads. Two standard deviations of the mean were chosen to represent a normal response at various levels of exercise. Analysis of the exercise heart rates in 172 patients who had CAD revealed 16 patients who had a peak exercise heart rate below 2 standard deviations of the mean. Of the 16 patients, 5 had 1-vessel, 5 had 2-vessel and 6 had 3-vessel CAD. Of 65 patients who had no significant ST-segment shift and who did not reach 85% of age-predicted heart rate, 13 (20%) had an inappropriately low heart rate for the work load performed. Each of the 13 patients had CAD. Of the 172 patients with CAD, those with chronotropic incompetence exercised further than the patients who did not have chronotropic incompetence (9.4 +/- 2.1 vs 7.0 +/- 3.4 METs, p less than 0.01). In conclusion, chronotropic incompetence is a relatively infrequent occurrence in an exercise test population; however, this finding, when present, is relatively specific for CAD, and may be useful in detecting patients with CAD who have an indeterminate exercise test.

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.

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)

Prognostic value of exercise thallium scintigraphy in patients with good exercise tolerance and a normal or abnormal exercise electrocardiogram and suspected or confirmed coronary artery disease.

Exercise thallium scintigraphy is widely used to assess prognosis in patients with suspected or proven coronary artery disease. The incremental prognostic value of this technique in patients who have good exercise tolerance has not been well studied. Two hundred ninety-nine patients with known or suspected coronary artery disease without prior myocardial infarction or revascularization procedure referred for exercise myocardial perfusion imaging and able to exercise to greater than or equal to stage III of the Bruce protocol were included. After a mean follow-up of 50 +/- 10 months, there were 15 cardiac events (5%). The incidence of cardiac events was 10 versus 3% (p less than 0.001) in patients with an abnormal versus normal thallium-201 scan, and 9 versus 3% (p = 0.03) for an abnormal versus normal exercise electrocardiogram. When the 185 patients with a normal exercise electrocardiogram were examined, the incidence of cardiac events was 3% (5 of 150) in patients with a normal scan versus 0% (0 of 35) in patients with an abnormal scan. In the 114 patients with an abnormal exercise electrocardiogram, an abnormal thallium-201 scan was predictive of cardiac events (18% [8 of 44] versus 3% [2 of 70]; p = 0.006). Stepwise logistic regression analysis selected an abnormal thallium-201 scan and abnormal exercise electrocardiogram, low peak exercise heart rate, and male gender as independent variables associated with a significant increased risk of cardiac events. Thus, in patients with known or suspected coronary artery disease and good exercise tolerance, the addition of thallium-201 imaging in patients with an abnormal exercise electrocardiogram provides useful prognostic information.(ABSTRACT TRUNCATED AT 250 WORDS)

Quality of life after coronary revascularization in the United States and Canada.

Cardiac procedures are performed less frequently in Canada than in the United States (US), yet rates of cardiac death and myocardial infarction are similar. We therefore sought to compare long-term symptoms and quality of life in Canadian and American patients undergoing initial coronary revascularization. The 161 patients enrolled in the Bypass Angioplasty Revascularization Investigation at the Montreal Heart Institute were compared with 934 patients enrolled at 7 US sites. Patients' outcomes were documented for 5 years after random assignment to percutaneous transluminal coronary angioplasty or coronary artery bypass graft surgery. Functional status was assessed using the Duke Activity Status Index. Canadian patients were significantly younger and had more angina at study entry. Death and nonfatal myocardial infarction were not significantly different between Canadian and US patients after adjustment for baseline risk. Canadian patients had significantly greater improvements in functional status at 1-year follow-up (Duke Activity Status Index score + 13.5 vs. + 6.0, p = 0.002), but this difference progressively narrowed over 5 years. Angina was equally prevalent in Canadian and US patients at 1 year (16% vs. 19%), but significantly more prevalent in Canadian patients at 5 years (36% vs. 16%, p = 0.001). Repeat revascularization procedures were performed less often over 5 years among Canadian patients (26% vs. 34%, p = 0.08), especially coronary artery bypass graft surgery after initial percutaneous transluminal coronary angioplasty (18% vs. 32%, p = 0.03). These results suggest more anginal symptoms are required in Canada before coronary revascularization, but as a result Canadians receive greater improvements in quality of life after the procedure.

Myocardial injury and bypass grafting. Value of serum enzymes in diagnosis.

To clarify the value of serum enzymes in the detection of intraoperative and postoperative myocardial injury associated with coronary artery bypass grafting, we evaluated 70 consecutive patients (151 grafts). We used electrocardiograms and serial determinations of serum levels: serum glutamic oxaloacetic transaminase (SGOT), creatinine phosphokinase (CPK), lactic dehydrogenase (LDH), and LDH isoenzymes on Days zero, 1, 3, 5, 7, and 10. Patency of all grafts 1 week postoperatively was 92 per cent. Fourteen patients (20 per cent) had ECG evidence of acute myocardial infarction (AMI) or ischemia lasting longer than 48 hours. This incidence of AMI was attendant with no deaths or discernible changes in postoperative ventriculography. LDH-1 (cardiac fraction) was elevated in all patients with myocardial injury. Late elevation of LDH-1 occurred in 2 patients at the time of postoperative catheterization, 1 of whom had negative findings on ECG. Diagnostic correlation was not observed with total LDH, CPK, or SGOT. Predisposing factors to AMI included preinfarction angina (4 of 14 patients), occluded grafts (4 of 14), and a bypass time greater than 120 minutes.

Late sequelae of perioperative myocardial infarction.

The late suquelae of myocardial injury occurring at the time of direct myocardial revascularization are unknown. Fifty of 500 consecutive patients undergoing aortocoronary bypass grafting developed both electrocardiographic and enzymatic evidence of myocardial injury. They were matched with 50 patients of similar age, sex, history of previous infarction, severity of angina, degree of coronary arteriosclerosis, and level of ventricular function as determined by preoperative angiographic studies. The conduct of the operation was identical in each group except for prolongation of total cross-clamp time in those patients with myocardial injury. The total number of vessels grafted, the conduit used, and the operative mean graft flow were similar. Results of treadmill stress testing at 24 to 36 months were not significantly different between groups. Angina status, long-term survival, graft patency, and ventricular function were not adversely affected by intraoperative myocardial injury. However, postoperative ventricular function and stress test performance were related to graft patency.

Quantitation of CK-MB release: diagnostic utility in coronary artery bypass grafting.

The quantitative release of creatine kinase (CK-MB) into the circulation of 97 patients receiving between three and five distal aorto-coronary bypass grafts was used to quantitate the minimal operative myocardial injury and to determine the diagnostic utility of this measurement in the detection of perioperative myocardial infarction. Independently read electrocardiography (ECG) was used to define infarction. The +/- SD confidence range for traumatized heart tissue based on 88 patients without infarction was 0-40.5 g equivalents. Six patients with perioperative myocardial infarction had values significantly above this range. Three patients with indeterminate ECG both released CK-MB significantly above the reference range and were clearly abnormal from a clinical standpoint.

Carbon monoxide exposure of subjects with documented cardiac arrhythmias.

The impact of low-level carbon monoxide exposure on ventricular arrhythmia frequency in patients with ischemic heart disease has not been thoroughly studied. The issue is of concern because of the potential proarrhythmic effect of carbon monoxide in patients with ischemic heart disease. We studied 30 subjects with well-documented coronary artery disease who had an average of at least 30 ventricular ectopic beats per hour over a 20-hour monitoring interval. By using appropriate inclusion and exclusion criteria, subjects were selected and enrolled in a randomized double-blind study to determine the effects of carbon monoxide exposure on ventricular arrhythmia frequency at rest, during exercise, and during ambulatory activities. The carbon monoxide exposure was designed to result in 3% or 5% carboxyhemoglobin levels, as measured by gas chromatography. The carbon monoxide exposure protocol produced target levels in 60 minutes, and the levels were maintained for an additional 90 minutes to provide adequate time to assess the impact of carbon monoxide on the frequency of ventricular ectopic beats. The data on total and repetitive ventricular arrhythmias were analyzed for seven specific time intervals: (1) two hours before carbon monoxide exposure; (2) during the two-hour carbon monoxide or air exposure; (3) during a two-hour rest period; (4) during an exercise period; (5) during an exercise recovery period; (6) six hours after carbon monoxide or air exposure; and (7) approximately 10 hours after exposure, or the remaining recording interval on the Holter monitor. There was no increase in ventricular arrhythmia frequency after carbon monoxide exposure, regardless of the level of carboxyhemoglobin or the type of activity. During steady-state conditions at rest, the number of ventricular ectopic beats per hour was 115 +/- 153 (SD) for room air exposure (0.7% carboxyhemoglobin), 121 +/- 171 for the lower carbon monoxide exposure (3.2% carboxyhemoglobin), and 94 +/- 129 for the higher carbon monoxide exposure (5.1% carboxyhemoglobin). The frequency of complex ventricular ectopy was not altered at the levels of carbon monoxide studied. Secondary analysis of the impact of carbon monoxide on ventricular ectopic beat frequency stratified by baseline ejection fraction, baseline ventricular ectopic beat frequency, and exercise-induced ST-segment changes did not indicate an effect of carbon monoxide on ventricular arrhythmias. In conclusion, low levels of carbon monoxide exposure resulting in blood levels of 3.2% and 5.1% carboxyhemoglobin, as measured by gas chromatography, do not have a proarrhythmic effect on patients with coronary artery disease and frequent ventricular ectopy.(ABSTRACT TRUNCATED AT 400 WORDS)

Clinical use of echocardiography: a review.

The clinical usefulness of echocardiography can be considered under a few broad categories: (a) measurement of internal structures and their changing relationships to each other throughout the cardiac cycle; (b) demonstration of abnormalities of function which are dependent on motion--for example, the prolapsing mitral leaflet or the paradoxical septal motion in right ventricular volume overload; and (c) changes within the heart such as pericardial effusion which lead to the development of echo-free spaces or the appearance of echo within a normally echo-free chamber as in myxoma.

Ambulatory (Holter) electrocardiography and myocardial ischemia.

Ambulatory (Holter) electrocardiography has evolved over the past two decades to allow accurate assessment of the cardiac rhythm, and more recently, accurate detection and measurement of ST segment changes. These ambulatory ECG ST segment changes that occur with and without symptoms, although thought to be of questionable clinical value for many years, have recently been clearly documented in coronary artery disease patients to represent true myocardial ischemia. Concurrent with these technologic developments has been an evolution of the pathophysiologic understanding of myocardial ischemia, and the relative role and sequential nature that ECG ST segment changes have in its development. This review examines from a clinical perspective the current understanding of the pathophysiologic sequence of development of myocardial ischemia, emphasizes the ECG diagnostic methods that detect this sequential change, examines the criteria that define ambulatory ECG myocardial ischemia, and discusses those nonischemic factors that affect the ECG ST segment and its interpretation. Moreover, an ever increasing number of ambulatory ECG studies of coronary artery disease and normal patients have defined unique characteristics of the ambulatory ECG ST segment changes observed with regard to its diagnostic, prognostic, and therapeutic assessment value in the study of myocardial ischemia.

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.

Real-time analysis ambulatory electrocardiography--clinical evaluation of cardiac arrhythmias by the Aegis system.

To evaluate the technical reliability, clinical applicability, and arrhythmia accuracy of one manufacturer's real-time analysis ambulatory ECG instrument (Aegis Medical Systems), 164 patients were simultaneously examined through a "Y" cable by both a real-time analyzer and a conventional Holter recorder. Technical failure was similar for both recorders (2% in each), and the real-time analyzer was applicable to all patients encountered. Using a randomly selected hand-counted database of 799 hours as the standard of truth, accuracy of the real-time analyzer for hourly mean heart rate, isolated ventricular ectopic beats, ventricular couplets, ventricular tachycardia, isolated supraventricular ectopic beats and supraventricular tachycardia was determined. Mean heart rate showed 96% agreement and a high correlation (r = .986) to hand-counted values. Real-time analysis overall sensitivity, positive predictive accuracy, and false positive rate for the Aegis Medical System were (a) for isolated ventricular ectopic beats--92%, 92%, and 8%, (b) for ventricular couplets--80%, 97%, and 3%, (c) ventricular tachycardia--81%, 92%, and 8%, (d) supraventricular ectopic beats--81%, 82%, and 18%, and (e) for supraventricular tachycardia--75%, 89%, and 11%. Arrhythmia analysis was valid for mean heart rate and ventricular arrhythmias, but showed lower sensitivities in detection of low prevalence (1-60 b/Hr) ventricular couplets (72%) and ventricular tachycardia (43%). Significant inaccuracies for some densities of supraventricular arrhythmia were also found. This study found the real-time analysis ambulatory ECG similar to conventional Holter recording for technical reliability and patient applicability. Given the limitations of currently available real-time analysis ambulatory ECG systems, it is a promising technology.

Survival patterns in clinical and angiographic subsets of medically treated patients with combined proximal left anterior descending and proximal left circumflex coronary artery disease (CASS).

Baseline, clinical, and angiographic features of 1014 Coronary Artery Surgery Study (CASS) registry patients with combined proximal left anterior descending and proximal left circumflex coronary disease were examined to define determinants of prognosis in this clinical high-risk patient subset. A stepwise Cox regression analysis identified congestive heart failure score, left ventricular contraction score, mitral regurgitation, age, and digitalis usage as independent variables predictive of 8-year survival. When patients were stratified by left ventricular contraction score, the 8-year survival rate was 62%, 49%, and 19%, respectively, for patients with a left ventricular score of 5 to 9, 10 to 14, and greater than or equal to 15 (p less than 0.0001). The presence of a stenosis greater than or equal to 70% in the right coronary artery was associated with worse survival (47% versus 54% at 8 years; p = 0.051). In conclusion, the diagnosis of combined proximal left anterior descending and left circumflex coronary artery disease represents a large prognostic spectrum that needs to be considered when counselling individual patients.