Possible inhibition of hepatic metabolism of quinidine by erythromycin.

OBJECTIVE: To present and analyze a patient case illustrating a possible drug interaction between quinidine and erythromycin. METHODS: This is a case report of one hospitalized patient. The setting for this analysis was a university hospital. Through a MEDLINE search of all English medical literature (1966 to 1994) documenting possible interactions between quinidine and erythromycin, retrospective patient chart review, and analysis of the relationship between serum quinidine concentrations and significant clinical events, deduce the possibility of a quinidine and erythromycin pharmacokinetic and pharmacodynamic interaction in this particular patient case. RESULTS: This case demonstrated a probable erythromycin-quinidine pharmacokinetic interaction that led to a decrease in quinidine apparent clearance, an increase in quinidine serum concentrations, and a possible quinidine toxicity. CONCLUSION: Serum quinidine concentrations, electrocardiograms, and other factors that may predispose patients to torsades de pointes, such as hypokalemia and hypomagnesemia, should be monitored closely if quinidine is coadministered with erythromycin.

Endocardial mapping during sinus rhythm in patients with coronary artery disease and nonsustained ventricular tachycardia.

Programmed stimulation in patients with nonsustained ventricular tachycardia (VT) and coronary artery disease (CAD) induces sustained VT in 30 to 50% of patients. The presence of inducible, sustained VT identifies patients at high risk for sudden death. This study sought to determine whether patients with nonsustained VT who have inducible, sustained VT would have differences of left ventricular endocardial activation and conduction compared with those of patients without inducible, sustained VT. Thirty-six patients with CAD referred for evaluation of nonsustained VT underwent programmed ventricular stimulation and catheter mapping of left ventricular endocardial activation. Using previously validated methods, electrograms were classified as normal, abnormal or fractionated based on measurement of local electrogram duration and amplitude. Programmed stimulation induced sustained, uniform VT in 16 of 36 patients (44%). Patients with inducible, sustained, uniform VT had significantly more sites with abnormal (48%) and fractionated (5.5%) electrograms than did those without inducible VT (35% abnormal and 0.4% fractionated; p = 0.05 and 0.01, respectively). Patients with inducible VT had a mean of 15% of mapped sites displaying late electrograms versus only 3% in those without inducible VT (p < 0.01). The duration of the longest local electrogram in patients with inducible, sustained, uniform VT was 128 ms compared with 100 ms in those without inducible VT (p < 0.001). Thus, patients with CAD presenting with nonsustained VT who have inducible, sustained, uniform VT have significantly greater degrees of local conduction slowing and delayed activation than do those without inducible, sustained, uniform VT. These observations support reentry as the mechanism of the induced arrhythmias in these patients.

Propafenone-induced liver injury.

OBJECTIVE: To describe propafenone-induced liver injury. DESIGN: Retrospective case report. SETTING: Referred care in a large tertiary care center. Laboratory tests were performed at the auxiliary site and the tertiary care center. PATIENT: A 71-year-old woman with atrial fibrillation developed elevations of greater than two times the upper limit of normal in alkaline phosphatase (ALK), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyltransferase (GGT) after initiation of propafenone therapy. INTERVENTIONS: Studies included serial measurements of ALK, ALT, AST, and GGT. RESULTS: The patient developed elevations of greater than two times the upper limit of normal in ALK, ALT, and AST, one month after initiating propafenone therapy. The propafenone dose was decreased from 900 to 675 mg/d and, ten days later, the ALK, ALT, and AST were decreased slightly, but still above the upper limit of normal. One month later, serum transaminases had returned to baseline, but propafenone therapy was discontinued because of recurrent atrial fibrillation, persistent elevation in ALK, and elevation in GGT. Two months after discontinuing propafenone, serum aminotransaminase and ALK concentrations had normalized and GGT had decreased and remained only slightly elevated. CONCLUSIONS: The occurrence of liver injury secondary to propafenone therapy is rare. Reported cases appear to be secondary to hepatocellular injury, cholestasis, or a combination of the two. In this case, the pattern demonstrated by elevations in liver enzymes may be classified as acute cholestatic liver injury. Because the reported incidence is 0.1-0.2 percent and there are no known fatalities secondary to propafenone liver injury, routine monitoring of liver function tests in all patients receiving propafenone cannot be recommended at this time. Baseline liver function tests prior to initiating propafenone therapy with follow-up laboratory studies one month later are recommended in patients with known liver dysfunction. If elevations are noted, a reduction in dose may result in lower liver enzyme concentrations, although discontinuation of therapy may be required in some cases.

Differences in electrophysiological substrate in patients with coronary artery disease and cardiac arrest or ventricular tachycardia. Insights from endocardial mapping and signal-averaged electrocardiography.

BACKGROUND: Many studies have combined patients with hemodynamically well-tolerated ventricular tachycardia (VT) and those with cardiac arrest (CA) as a single, homogenous group. Recent studies suggest that these two groups have different electrophysiological substrates and responses to therapy. Most of these studies, however, enrolled patients with a variety of cardiac diagnoses. METHODS AND RESULTS: We used signal-averaged electrocardiography (SAECG) and endocardial catheter mapping to define the electrophysiological substrate in patients with coronary artery disease and VT or CA and correlate the results of the two methods. We also examined the usefulness of SAECG in CA patients to differentiate those with inducible arrhythmias from those who are noninducible. VT patients were more likely to have had a prior myocardial infarction (p = 0.0005) and to have inducible arrhythmias (p = 0.0001) than were CA patients. The induced arrhythmias in patients who presented with VT was VT in more than 90% of cases, whereas in CA patients, polymorphic ventricular tachycardia (PMVT) accounted for one third of induced arrhythmias. Mean filtered QRS duration was longer (135 versus 120 msec) and the terminal QRS voltage was smaller (20 versus 34 microV) in VT than in CA patients (p less than 0.01). Sixty-three percent of CA patients and 87% of VT patients had abnormal SAECG (p = 0.001). VT patients had more extensive endocardial abnormalities and more abnormal (53% versus 40%, p = 0.002), fractionated (8% versus 3%, p = 0.02), late (17% versus 8%, p = 0.0003), and late abnormal or fractionated (14% versus 4%, p = 0.0001) sites than CA patients. VT patients had a greater duration of the longest electrogram (129 versus 109 msec, p = 0.0006) and total endocardial activation time (68 versus 54 msec, p = 0.009). Among CA patients, those with induced VT had more extensive substrate than did those with induced PMVT and were similar to VT patients with induced VT. Among CA patients, the trend for more patients with inducible VT (77%) or PMVT (55%) than noninducible patients (47%) to have an abnormal SAECG did not reach statistical significance (p = 0.14). The positive and negative predictive values of an abnormal SAECG were 77% and 44%, respectively. CONCLUSIONS: VT patients have more extensive endocardial substrate than CA patients, which translates into greater and more frequent SAECG abnormalities. Among CA patients, there are significant differences in substrate between patients with induced VT and those with induced PMVT. SAECG is not useful in differentiating CA patients who have inducible VT or PMVT from those who do not.

Therapy for coronary heart disease in women.

Both the presentation and prognosis of coronary heart disease in women are significantly different than in men. Diagnostic evaluations should be approached somewhat differently in male and female populations, and gender should be one of the variables assessed when options for medical and surgical therapy are considered. Risk factor modification can be offered as a potentially effective form of therapy for coronary heart disease in women. These modifications would include cessation of smoking, avoidance of oral contraceptives in women greater than 35 years of age, hypertension control, and normalization of blood lipid profile and body weight. Risk factor modification may be particularly important in prevention of accelerated atherosclerosis in diabetic women. Prognosis after myocardial infarction is significantly worse in women despite better post-infarction left ventricular ejection fraction and higher incidence of non-Q-wave myocardial infarction in that population. Definitive assessment of coronary anatomy and aggressive management of coronary heart disease should be considered in women judged to be at high risk. Little information is available regarding gender-specific responses to medical management of coronary heart disease. Women seem to have a less favorable short-term outcome after PTCA, but better long-term results. Coronary artery bypass grafting results appear to depend less on gender than on coronary anatomy, preoperative risk factors, and patient size, and thus should not be withheld from women.

Nonuniform recovery of excitability in the left ventricle.

The purpose of this study was to determine left ventricular activation, dispersion of refractoriness, and total recovery time in patients with coronary artery disease and ventricular tachycardia and in patients with the long QT syndrome and to compare these patients with a group of normal patients. Left ventricular endocardial catheter mapping and left ventricular refractory period determination were performed in 18 patients. Group 1 consisted of seven patients with no heart disease and no arrhythmia; group 2 consisted of six patients with previous infarction and sustained ventricular tachycardia; and group 3 consisted of five patients with prolonged QT interval and previous cardiac arrest. Total left ventricular endocardial activation was significantly longer in group 2 (75 +/- 23 msec, mean +/- SD) compared with group 1 (34 +/- 9 msec, p less than 0.01) and group 3 (42 +/- 5 msec, p less than 0.05). Dispersion of refractoriness was significantly greater in group 3 (87 +/- 27 msec) than in group 1 (40 +/- 14 msec, p less than 0.01) and group 2 (53 +/- 14 msec, p less than 0.05). Dispersion of total recovery time was significantly greater in group 2 (90 +/- 30 msec) than in group 1 (52 +/- 14 msec, p less than 0.05) as well as group 3 (114 +/- 43 msec) compared with group 1 (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of individual and combined effects of procainamide and amiodarone in patients with sustained ventricular tachyarrhythmias.

To compare the individual and combined electrophysiological effects of amiodarone and procainamide, 35 patients with sustained ventricular arrhythmias underwent programmed stimulation in the control state, after procainamide (mean concentration, 8.7 +/- 2.8 micrograms/ml), after 13 +/- 2 days of amiodarone (1,400 mg/day x 7 days, then 400 mg/day), and after amiodarone with procainamide (mean procainamide concentration, 7.8 +/- 2.2 micrograms/ml). Sustained ventricular tachycardia (VT) was inducible in all 35 patients during treatment with procainamide alone and with amiodarone alone. Procainamide and amiodarone similarly increased the VT cycle length (+68 vs. +61 msec), the corrected QT interval (+63 vs. +49 msec), and the ventricular effective refractory period measured at paced cycle lengths of 600-550 msec (+23 vs. +21 msec) and 400 msec (+25 vs. +23 msec). Procainamide had a more pronounced effect on QRS duration than amiodarone during sinus rhythm (+18 vs. +8 msec, p less than 0.01) and during paced cycle lengths of 600-550 msec (+32 vs. +23 msec, p less than 0.01) and 400 msec (+37 vs. +28 msec, p less than 0.1) but a similar effect on the QRS duration during VT (+32 vs. +29 msec). During combination therapy, VT initiation was prevented in only two (6%) patients. The combination therapy produced a greater increase (p less than 0.001) than individual therapy in all the electrophysiological intervals assessed, with the exception of the sinus cycle length. On each drug regimen, a cycle length-dependent increase (p less than 0.05) in paced QRS duration was noted (400 more than 600-550 msec).(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiographic criteria for ventricular tachycardia in wide complex left bundle branch block morphology tachycardias.

Four electrocardiographic criteria for ventricular tachycardia (VT) were proposed and evaluated. These included (1) an R wave in V1 or V2 of greater than 30-ms duration; (2) any Q wave in V6; (3) a duration of greater than 60 ms from the onset of the QRS to the nadir of the S wave in V1 or V2 and (4) notching on the downstroke of the S wave in V1 or V2. The data showed that all 4 criteria had high predictive accuracy (96 to 100%) and specificity (94 to 100%). The relatively low sensitivities of the 4 criteria alone (30 to 64%) might limit their efficacy. Grouped criteria, however, could differentiate VT from supraventricular tachycardias with high sensitivity, specificity and predictive accuracy. The amount of tracings having either electrocardiographic criteria (1) or (2) or (3) or (4) was determined. The proposed combined criteria had a sensitivity of 100%, specificity of 89% and a predictive accuracy of 96%. Left axis deviation alone was of no value in distinguishing VT from supraventricular tachycardia. Characteristic patterns were present for left bundle branch block pattern VT associated with anterior and inferior myocardial infarction. In conclusion, the 12-lead electrocardiogram alone, when systematically analyzed, can be used to accurately diagnose the origin of wide complex tachycardias with left bundle branch block pattern. Attention to these criteria may lead to more rapid and effective therapy.

Predictive accuracy of criteria for chronic myocardial infarction in pacing-induced left bundle branch block.

Sensitivity, specificity and predictive accuracy of 5 electrocardiographic criteria for chronic myocardial infarction (MI) in the presence of left bundle branch block (LBBB) were evaluated in 47 patients with known (clinical and electrocardiographic Q wave) MI and 28 patients without MI. Two right ventricular sites were paced (producing LBBB with normal or left axis). The effect of infarct location on these criteria was also evaluated. In patients with LBBB: Cabrera's sign (notching of the upstroke of S wave in V3,4,5) is seen more often with MI than without (anterior more often than inferior), and the left axis increased its sensitivity. Chapman's sign (notching of upstroke of the R wave in I, L or V6) is more common in patients without MI, and its specificity and sensitivity are not altered by axis. Sensitivity of notching in 2, 3, F is too low to be clinically useful. Q 2, 3, F indicates only left axis; predictive accuracy for MI is high (100%) only for normal axis where sensitivity is low (3%). (5) Q 1, L, V6 is no more frequent with MI than without, but if MI is present it is more common in anterior than inferior infarction. Specificity and predictive accuracy are too low to be clinically useful as indicators of MI.