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.

Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation Investigators.

BACKGROUND: Nonrheumatic atrial fibrillation is common among the elderly and is associated with an increased risk of stroke. We investigated whether anticoagulation with warfarin would reduce this risk. METHODS: We conducted a randomized, double-blind, placebo-controlled study to evaluate low-intensity anticoagulation with warfarin (prothrombin-time ratio, 1.2 to 1.5) in 571 men with chronic nonrheumatic atrial fibrillation; 525 patients had not previously had a cerebral infarction, whereas 46 patients had previously had such an event. The primary end point was cerebral infarction; secondary end points were cerebral hemorrhage and death. RESULTS: Among the patients with no history of stroke, cerebral infarction occurred in 19 of the 265 patients in the placebo group during an average follow-up of 1.7 years (4.3 percent per year) and in 4 of the 260 patients in the warfarin group during an average follow-up of 1.8 years (0.9 percent per year). The reduction in risk with warfarin therapy was 0.79 (95 percent confidence interval, 0.52 to 0.90; P = 0.001). The annual event rate among the 228 patients over 70 years of age was 4.8 percent in the placebo group and 0.9 percent in the warfarin group (risk reduction, 0.79; P = 0.02). The only cerebral hemorrhage occurred in a 73-year-old patient in the warfarin group. Other major hemorrhages, all gastrointestinal, occurred in 10 patients: 4 in the placebo group, for a rate of 0.9 percent per year, and 6 in the warfarin group, for a rate of 1.3 percent per year. There were 37 deaths that were not preceded by a cerebral end point--22 in the placebo group and 15 in the warfarin group (risk reduction, 0.31; P = 0.19). Cerebral infarction was more common among patients with a history of cerebral infarction (9.3 percent per year in the placebo group and 6.1 percent per year in the warfarin group) than among those without such a history. CONCLUSIONS: Low-intensity anticoagulation with warfarin prevented cerebral infarction in patients with nonrheumatic atrial fibrillation without producing an excess risk of major hemorrhage. This benefit extended to patients over 70 years of age.

Procainamide-induced lupus anticoagulant.

The lupus anticoagulant, with or without other symptoms or signs of lupus, has been described in patients taking procainamide. Screening all such patients for the presence of these anticoagulants may be warranted (despite the rarity of episodes of bleeding) in view of the potentially increased risk of thrombotic events in patients who may already be predisposed. A prospective study to determine the incidence of lupus anticoagulant in procainamide-treated patients and the true frequency of thrombosis in these patients would be helpful in determining appropriate management.

Pindolol therapy for bradycardia/tachycardia syndrome.

Bradycardia/tachycardia syndrome (BTS) is notoriously refractory to drug therapy. Three patients with BTS unresponsive to digitalis or digitalis plus verapamil (ventricular response continued intermittently rapid despite prolonged pauses) were prescribed oral pindolol, a beta blocker with intrinsic sympathomimetic activity. The ventricular rate was well-controlled in all and no adverse effects were seen. Pindolol may be of value in selected patients with BTS.

The preoperative electrocardiogram as an indicator of risk in major noncardiac surgery.

In this series of 198 patients studied prospectively before major noncardiac surgery, we previously reported that an abnormal preoperative electrocardiogram was a statistically significant independent predictor of an increased risk of postoperative complications, i.e., death, myocardial infarction, or myocardial ischemia. We therefore carried out a detailed analysis of the preoperative electrocardiographic (ECG) findings using Minnesota code criteria. Both ST-T abnormalities and intraventricular conduction delays showed a statistical trend toward a higher frequency in patients with a complicated vs. an uncomplicated postoperative course (82% vs. 59% and 24% vs. 7%, respectively). Although only a minority of patients with either ECG finding actually developed a complication (22% and 40% respectively), the preoperative ECG appears to be a useful screening method, with ST-T abnormalities and intraventricular conduction delays identifying patients at increased risk for postoperative complications.

Beta-blockers in congestive cardiomyopathy. Conceptual advance or contraindication?

The precise role of adrenergic activity in congestive cardiomyopathy has not been established. A number of mechanisms through which increased catecholamine levels may be harmful, along with the clinical and experimental evidence supporting this concept, are summarized in this review. In this context, the suggestion that beta blockers may be beneficial for patients with severe heart failure, despite their well-known propensity to decrease cardiac contractility, can be better understood. Published reports on the use of beta blocker therapy for congestive cardiomyopathy now include approximately 200 patients, but have yielded inconsistent results. Non-randomized trials in Sweden have suggested increased survival, with most patients having improved functional status while receiving beta blockade, although improvement may take three to six months to become evident. The Swedish group also reported clinical deterioration after discontinuation of beta blockade. Two recent randomized trials in America yielded promising results, but the unexpectedly low mortality in the placebo groups emphasizes the critical importance of concurrent controls. Unfavorable reports have involved small groups with short-duration therapy. Even in these reports, overt aggravation of clinical heart failure has been quite infrequent but sometimes profound. As large scale trials are undertaken, an obvious goal is the development of methods to differentiate the patients with congestive cardiomyopathy who will benefit in response to beta blocker therapy from the few patients who will have a serious adverse response.

Technetium-99m-pyrophosphate scintigraphy in patients with suspected acute myocardial infarction: impact of interobserver variability.

Technetium-99m-pyrophosphate (TcPYP) scintigraphy may have great value in patients with suspected acute myocardial infarction (AMI), but interobserver variability undoubtedly has adverse impact on predictive value. TcPYP scintigrams for 133 (80%) of 166 consecutive patients admitted for suspected AMI were interpreted independently by three experienced readers. Although there was complete agreement for 87 interpretations (65%), major discrepancies (i.e., at least one positive and one negative reading on the same scan) occurred for 28 scans (21%). To assess predictive accuracy, patients were categorized as follows: 36 had definite AMI manifest by new ECG Q waves and/or CK-MB evidence of AMI (group I), 56 were classified as possible AMI (group II), and 41 had AMI excluded (group III). Using only the definitive diagnostic categories (groups I and III), accuracy for each reader approximated 0.68, with no single reader being correct more often than any other.

Transcutaneous temporary pacing in the operating room.

The safety and efficacy of transcutaneous temporary pacing were assessed in 21 patients undergoing elective surgical procedures under general anesthesia. Complete capture was achieved in all patients. The pacing threshold was 50 mamp in two patients, 100 mamp in nine, and 200 mamp in ten. The threshold was influenced by electrode position and also, possibly, by age, heart size, and chest size. No adverse effects of pacing were encountered. Transcutaneous pacing is a rapid, safe, and effective means of temporary pacing in the operating room.

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.

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.

Quinidine saliva concentrations: absence of correlation with serum concentrations at steady state.

Serum and saliva quinidine concentrations were measured in eight subjects with cardiac arrhythmias on various dosage regimens. There was good correlation between serum and saliva quinidine concentration after a single dose, but there was no such relationship after repeated dosing. Comparison of the area under a hysteresis loop, obtained by plotting the saliva/serum quinidine concentration ratio as a function of serum quinidine concentration over a dosing interval, indicated an exponential increase with increasing mean serum quinidine concentration. Salivary quinidine concentration predictions based on the Henderson-Hasselbalch equation did not correlate with the serum quinidine concentration under the steady-state conditions. These data suggest that quinidine concentration in saliva is not a direct reflection of its serum concentration in cardiac patients on maintenance (steady-state) therapy and hence not useful for therapeutic drug monitoring.

Respiratory arrest following first dose of timolol ophthalmic solution.

Within 30 minutes of the administration of his first dose of timolol ophthalmic solution, a 67-year-old man with stable chronic obstructive pulmonary disease experienced severe dyspnea leading to respiratory arrest. He recovered after endotracheal intubation and mechanical ventilation. Patients with bronchospastic pulmonary disease who are candidates for therapy with timolol ophthalmic solution should receive their first dose under medical supervision and should have continued close medical follow-up for as long as they receive timolol.

Acute changes in infranodal conduction time following left ventriculography and sublingual nitroglycerin administration in man.

During diagnostic cardiac catheterization for the evaluation of chest pain, His bundle electrograms were obtained in 32 male patients before and 2 to 5 minutes after each of two interventions known to acutely affect left ventricular volume and left ventricular end-diastolic pressure (the injection of 40 to 60 cc of contrast medium during left ventriculography and the administration of 0.4 mg of sublingual nitroglycerin). Changes in left ventricular end-diastolic pressure (18 +/- 6 vs 30 +/- 7 mm Hg, p less than 0.001 following ventriculography and 32 +/- 8 vs 19 +/- 8 mm Hg, p less than 0.005 following nitroglycerin administration) were accompanied by parallel alterations in HQ (48 +/- 8 vs 54 +/- 10 msec, p less than 0.005 following ventriculography and 57 +/- 10 vs 53 +/- msec, p less than 0.005 following nitroglycerin administration), but there were no significant changes in atrioventricular (AV) nodal conduction (AH). Significantly greater changes in HQ were seen in patients with triple-vessel coronary artery disease than in the remainder of the population, although there was clinical and/or ECG evidence of ischemia in only one patient. We conclude that factors other than progression of intrinsic conduction system disease may affect infranodal conduction. HQ should be interpreted cautiously in situations with rapidly changing hemodynamics, especially in patients with severe coronary artery disease.

Routine serum enzyme tests in the diagnosis of acute myocardial infarction. Cost-effectiveness.

To determine the cost-effectiveness of routine use of serial SGOT, lactic dehydrogenase (LDH), and LDH isoenzyme determinations in patients with suspected acute myocardial infarction (AMI), 166 consecutive patients admitted to a coronary care unit were prospectively identified and clinical findings analyzed independently using predetermined criteria. Based on chest pain characteristics, ECG, and creatine kinase--MB (CK-MB) results, patients were placed in categories of definite AMI (31%), possible AMI (34%), or AMI excluded (36%). The SGOT and/or LDH patterns were considered positive (ie, suggestive of AMI) in 82% of the patients with definite AMI but only confirmed CK-MB results. Positive SGOT/LDH results yielded new clinically relevant information in only 14 patients (8%). Total charges for SGOT/LDH determinations in these 166 patients totaled $10,938 or approximately $780 for each additional clinically important positive result. When serial ECG and CK-MB results are available, routine serial SGOT/LDH determinations are not justified.

Serum creatine kinase in the diagnosis of acute myocardial infarction. Optimal sampling frequency.

To document optimal sampling frequency, we reviewed creatine kinase (CK) myocardial specific isoenzyme (CKMB) results in 314 patients with suspected acute myocardial infarction (MI). In 127 patients with elevated CK/CKMB, peak CK observed using all samples (every four-hour [Q4hr] method) was compared with results that would have been obtained had samples been taken on admission and either twice daily (every 12-hour [Q12hr] method) or once daily (every 24-hour [Q24hr] method). Although average peak CK was statistically different (Q4hr greater than Q12hr greater than Q24hr), major underestimation of peak CK (greater than or equal to 500 units/L) was uncommon (3%) using the Q12hr method, suggesting that Q12hr sampling is a practical, cost-effective approach for patients with suspected acute MI.

Collateral circulation in patients with unstable angina.

Coronary collaterals were evaluated in 218 consecutive catheterized patients with unstable angina (defined as ischemic cardiac pain at rest associated with transient electrocardiographic changes). Collaterals were present in 106 patients (49 percent). The presence of collaterals correlated with the extent and severity of the coronary artery disease but not with age, sex, or risk factors. Among patients with comparable severity of narrowings, the presence of collaterals did not appear to protect against abnormal wall motion or pathologic Q waves on the ECG. In patients with single vessel disease, collaterals also did not appear to protect against transient ST segment evaluation during ischemia.