Nathan H. Carliner

Routine preoperative exercise testing in patients undergoing major noncardiac surgery

A prospective study of preoperative exercise testing was carried out in 200 patients older than 40 years scheduled for elective major noncardiac surgery under general anesthesia. The exercise test response was electrocardiographically positive in 32 patients (16%) (2 patients had a markedly positive test), equivocal in 11 patients (5.5%) and negative in 157 patients (78.5%). The patients were followed with serial pre- and postoperative electrocardiograms (ECGs) and determinations of serum creatine kinase (CK) and CK-MB. Six patients (3%) had primary endpoints: 3 (1.5%) died postoperatively and 3 (1.5%) had definite postoperative myocardial infarction. Secondary endpoints of suspected postoperative myocardial ischemia/injury diagnosed by ECG or elevation in CK-MB levels occurred in 27 patients (14%). Endpoint events were more common in patients aged 70 years or older. Endpoint events were also more common in patients with an abnormal (positive or equivocal) preoperative exercise test response than in those with a negative response (27% vs 14%); however, preoperative exercise results were not statistically significant independent predictors of cardiac risk. Using multivariate analysis, the only statistically significant independent predictor of risk was the preoperative ECG. Endpoint events were more common in patients with an abnormal than in those with a normal ECG (23% vs 7%, p less than 0.002). Because the results of exercise testing do not appear to add substantially to the risk separation provided by the ECG at rest, exercise testing is not recommended as a routine preoperative method for assessing perioperative risk in older patients who are being evaluated before major elective noncardiac surgery under general anesthesia.

Clinical indicators of left main coronary artery disease in unstable angina.

Two hundred consecutive catheterized patients with unstable angina pectoris were reviewed to find clinical and noninvasive indicators of left main coronary artery disease (greater than or equal to 50% lesion). Thirty-five patients (17.5% of total) had left main coronary artery disease. There were no differences between patients with and without left main coronary artery disease in age, sex, results of resting electrocardiogram, congestive heart failure, dyspnea during pain, duration of longest pain, arrhythmias, response to medical therapy, or other risk factors. Crescendo angina pectoris (worsening of pre-existing angina), transient ST-segment depression with pain, simultaneous anterior and inferior ST changes during pain, and fluoroscopic calcification of the left main coronary artery were all significantly more common in patients with left main coronary artery disease. However, low sensitivity or low predictive value, or both, limit the usefulness of these clinical predictors. Left main coronary artery disease cannot be reliably predicted in patients with unstable angina pectoris before coronary arteriography.

Cibenzoline plasma concentration and antiarrhythmic effect

The relationship between plasma concentrations of cibenzoline and its antiarrhythmic effect was evaluated in patients receiving the drug orally as part of an ascending multiple dose efficacy and tolerance study. Twenty‐five patients participated in a 3‐day placebo period, 3 days of 32.5 mg cibenzoline every 6 hr, 3 days of 65 mg cibenzoline every 6 hr, 3 days of 81.25 mg cibenzoline every 6 hr, and 3 final placebo days. Arrhythmia frequency was monitored by 24‐hr Holter monitoring and blood samples were drawn during and after dosing. Percent reduction in baseline premature ventricular complex (PVC) frequency for the 25 subjects demonstrated considerable interpatient variability in antiarrhythmic response. Cibenzoline plasma concentrations over 300 ng/ml were associated with some decrease in PVC frequency in virtually all cases. The relationship between plasma concentration and PVC frequency was studied more rigorously in eight of the 25 patients and that for ventricular couplet (VC) frequency was studied in six. For these analyses, PVC and VC frequency data were averaged over 6‐hr intervals and plotted against trough cibenzoline concentrations. The data from each patient were fitted with a concentration‐effect function (Hill equation) by means of least squares regression. With the exception of two extreme values, the concentration corresponding to 90% reduction in PVC frequency (C90) ranged from 215 to 405 ng/ml. In five of the six patients with arrhythmia in whom VC data were also evaluated, the individual C90 for VCs were considerably less than those for PVCs. The agreement between the observed concentration‐response relationships and those predicted by curve‐fitting the data suggests that the antiarrhythmic effect of cibenzoline is proportional to its plasma concentration, and that the Hill equation provides an accurate mathematic description of the concentration‐response relationship.

Late Unheralded Pacemaker Pocket Infection Due to Staphylococcus epidermidis: A New Clinical Entity

Late pacemaker pocket infections in the absence of predisposing factors such as multiple pacemaker related procedures, skin erosion, chest wall trauma or generalized sepsis have been rarely reported. In the past year, we have seen three late pocket infections (18, 32 and 47 months post‐implanlafion) due to Staphylococcus epidermidis (S. epidermidis). All three patients with late S. epidermidis infections presented with painless swelling over the pulse generator site and had been well until shortly before admission. The patients denied febrile illnesses or chest trauma in the preceding year and no skin erosion was evident. All had been seen regularly in clinic and bimonthly transtelephonic recordings had shown normal pacemaker function. Local drainage, antibiotics and removal of the pacing system was successful in all three patients. We conclude that late pacemaker pocket infections due to S. epidermidis may become an imporlanf clinical problem in this era of long‐lasting pulse generators. In light of the insidious nature of S. epidermidis infections, regular inspection of the pocket area by both patient and physician is mandatory. (PACE, Vol. 5, March‐April, 1982)

Relation of ventricular premature beat suppression to serum quinidine concentration determined by a new and specificassay

Fourteen patients who were receiving quinidine in doses of 800 to 1800 mg. per day for ventricular arrhythmias underwent Holter monitoring during a steady state dosing interval at a mean of four days after the initiation of quinidine therapy. Serum quinidine concentration, determined by a specific high performance liquid chromatography method, was measured hourly during the dosing interval. Ventricular premature beat (VPB) frequency during quinidine therapy was compared to the baseline VPB frequency. A reduction in VPB frequency of at least 90% was required to substantiate the presence of a therapeutic response to quinidine. In 12 of the 14 patients a therapeutic response to quinidine was present at serum levels ranging from 0.72 to 5.92 micrograms/ml. There was no group correlation between serum quinidine concentration and VPB frequency, but there was a tendency in individual patients for VPB frequency to decrease as serum quinidine level increased. Quinidine toxicity was not observed in these 14 patients. Because of the wide variation in response to quinidine, a serum quinidine concentration that is within the therapeutic range is not necessarily the optimal serum quinidine concentration for an individual patient. The clinician may therefore consider increasing the dose if there is no evidence of quinidine toxicity and the ventricular rhythm disturbance is not adequately controlled.

Overdrive pacing for atrial flutter.

To determine the incidence and predictors of conversion to normal sinus rhythm, a total of 124 procedures using a standard pacing protocol were performed in 101 consecutive inpatients referred for pace termination of atrial flutter. Normal sinus rhythm was achieved in 75 pace termination procedures (60%), including 10 in which atrial fibrillation occurred initially and later converted spontaneously. Sustained atrial fibrillation was provoked in 39 procedures, and atrial flutter persisted in 10. Clinical and laboratory parameters, including use of antiarrhythmic drugs, were not helpful in predicting the outcome of pacing. Of 17 patients undergoing repeat pacing for recurrent flutter, concordant results were obtained in only 4. It is concluded that: (1) overdrive pacing is only a moderately effective means of restoring sinus rhythm in patients with atrial flutter, although some change in rhythm occurs in the vast majority; (2) pacing-induced atrial fibrillation may be unstable and spontaneously converts to sinus rhythm in > 20% of cases; (3) there are no clinically useful predictors of success; (4) antiarrhythmic drugs do not facilitate pacing-induced conversion to sinus rhythm; and (5) failure to convert to sinus rhythm with 1 episode of flutter does not preclude success on subsequent occasions.

Pharmacokinetics of Oral Cibenzoline in Arrhythmia Patients

SummaryThe pharmacokinetics of oral cibenzoline were studied in 30 arrhythmia patients as part of an ascending multiple-dose efficacy study. The elimination half-life of the drug following repetitive dosing ranged from 7.6 to 22.3 hours, with a harmonic mean of 12.3 hours (n = 24), and increased with age and decreasing renal function. The drug exhibited apparent dose proportional and linear pharmacokinetics over the range of doses studied. Multivariate analysis revealed that the patients’ age and serum creatinine concentration accounted for 71% of the variability in the range of β values (terminal elimination rate constant), and that 69.5% of the intersubject variability in the steady-state trough plasma concentrations could be accounted for by the patients’ age, weight and serum creatinine concentration.These data suggest that, although there is some intersubject variability in the elimination and accumulation of cibenzoline, much of the variability can be explained by the patients’ age, weight and renal function.

Left anterior fascicular block: Electrocardiographic criteria for its recognition in the presence of inferior myocardial infarction☆

Although the vectorcardiographic criteria for recognizing left anterior fascicular block in the presence of inferior myocardial infarction are well established, comparable electrocardiographic criteria have not been studied. From vectorcardiographic criteria, it was hypothesized that in patients with left axis deviation but without bundle branch block the presence of a deep negative terminal deflection (S wave) in lead II accompanied by a positive terminal deflection (r wave) in lead aVR should indicate left anterior fascicular block whether or not inferior infarction is present. The electrocardiograms of 75 patients with unequivocal vectorcardiographic evidence of either left anterior fascicular block or inferior infarction, or both, were reviewed. Of the 47 patients who met strict vectorcardiographic criteria for left anterior fascicular block, 44 (94 percent) showed the predicted electrocardiographic pattern, including 24 of 26 (92 percent) who had both this conduction defect and inferior myocardial infarction. There was only one patient with vectorcardiographic evidence of inferior myocardial infarction alone with the findings of left axis deviation and the electrocardiographic pattern of combined infarction and fascicular block (that is, only one false positive). Thus, if bundle branch block is excluded, the proposed electrocardiographic pattern permits recognition of left anterior fascicular block whether or not there is coexistent inferior myocardial infarction.

Systemic Sarcoidosis and Electrocardiographic Conduction Abnormalities: Electrophysiologic Evaluation of Two Patients

Two patients with long histories of sarcoidosis had progression of conduction abnormalities to heart block and severe bradycardia. Conduction system involvement was trifascicular in both patients, though evidence for left ventricular functional impairment was otherwise lacking. Sudden death is seen more commonly in patients with sarcoidosis who have diffuse myocardial involvement, while conduction abnormalities can occur with relatively localized disease.

Quinidine therapy in hospitalized patients with ventricular arrhythmias

Quinidine serum levels and pharmacokinetic data were assessed during steady state therapy with oral quinidine sulfate in 19 hospitalized patients who were being treated for ventricular arrhythmias. A new high performance liquid chromatography assay was employed. Four patients were studied both after the first dose of quinidine and at steady state, and the initial dose pharmacokinetic values were found not to be predictive of steady state. The mean half-life of quinidine was 4.5 hours, but there was wide individual variation. The elimination rate constant for quinidine was significantly lower in patients with echocardiographic evidence of left ventricular dilatation than in patients with normal echocardiographic left ventricular size. The average urinary excretion of quinidine was only 11.3%. The pharmacokinetic data in seven chronic alcoholic patients without clinical or laboratory evidence of hepatic insufficiency did not differ from the data obtained in nonalcoholic patients. However, with severely impaired liver function, there may be marked prolongation of quinidine half-life predisposing to quinidine toxicity. The possible clinical implications of these findings are discussed.