Graded exercise testing in patients with sinus node dysfunction.

Serial measurements of heart rate and oxygen uptake were obtained before and during maximal upright graded bicycle stress testing in 16 patients, 10 to 77 years old (mean 46 years), with sinus node dysfunction; five had permanent and two had temporary demand ventricular pacemakers. In 15 patients, including those with pacemakers, maximal exercise was performed before and after the intravenous administration of 1 mg atropine. Maximal exercise was terminated because of cerebral symptoms in seven (three had effort-induced tachyarrhythmias and one had autonomic insufficiency), fatigue in five (one had effort-induced heart block), heart failure in three and angina pectoris in one. With maximal exercise, patients with sinus node dysfunction were unable to obtain maximal heart rates or oxygen uptakes comparable to age- and sex-matched control subjects. Additionally, maximal oxygen uptake did not differ significantly between patients with or without pacemakers even when ventricular pacing rates were increased (two instances). The administration of atropine increased the resting heart rate, but the maximal heart rate and oxygen uptake achieved during maximal exercise did not differ significantly from those obtained before the administration of atropine in the patient and control groups. Physically active patients with sinus node dysfunction have diminished exercise capacity due in part to cardiac arrhythmia, latent or overt cardiac failure, or autonomic dysfunction.

Clinical and electrophysiological effects of intravenous quinidine in man.

Quinidine gluconate (total dose 4-4 to 9-1 mg/kg) was infused intravenously over 22 minutes in 20 patients with either frequent premature ventricular contractions or supraventricular arrhythmias, 16 of whom had bundle-branch block. Therapeutic plasma quinidine levels (3 to 7 mg/l) were achieved in 15. Heart rate, atrioventricular nodal, and infranodal conduction times did not change significantly. The QRS duration increased significantly from 128+/-30 to 134+/-29 ms at peak plasma quinidine levels (P less than 0.01). Mild hypotension occurred during infusion in most patients. Two patients had a severe but transient toxic response characterised by hypotension, nausea, vomiting, and diaphoresis. Atrioventricular dissociation with escape His bundle or fascicular rhythm occurred in 1 patient with sinus bradycardia. Bundle-branch block does not contraindicate administration of quinidine. Quinidine gluconate administered intravenously (0-3 to 0-4 mg/kg per min) is frequently associated with hypotenstion and should be used only in an intensive care setting and with careful monitoring of blood pressure.

Echocardiographic appearance of ruptured aortic cusp.

Serial echocardiograms of a patient with enterococcal endocarditis and aortic insufficiency suggested the presence of vegetations on the aortic valve with progression of the lesion to frank prolapse of an aortic valve cusp. At surgery, the patient was found to have a flail noncoronary cusp to which an 8 mm vegetation was adherent. Anatomic correlations are presented, and a possible mechanism for the unusual echographic findings is discussed.

Atrial pacing in patients with sinus node dysfunction.

Sinus nod recovery time (SNRT) at paced atrial rates of 100 (SNRT100) and 120 (SNRT120) beats/min, atrial effective refractory periods at spontaneous heart rates (AERP) and at paced rates of 100 (AERP100) and 120 (AERP120) beats/min, and premature atrial stimulation were among the studies in evaluating 33 patients with symptomatic sinus node disease and 42 normal subjects. Although mean SNRT100 and SNRT120 were statistically significantly greater in patients than in control subjects, there was a significant overlap between patient and control groups, and SNRT100 or SNRT120 was associated with a 30.3 per cent false-negative and 5 per cent false-positive incidence. Correction for heart rate (SNRT-spontaneous cycle length) failed to improve the sensitivity or specificity of this test. There was no significant difference in mean AERP, AERP100 or AERP120, or in sinoatrial conduction time in patients compared with control subjects. Analyses of curves derived from plots of test and return cycles showed abnormal curves in only five of the 24 patients studied by progressively premature atrial stimulation. Two of these five patients showed normal zone I and II phenomena followed by a progressive linear increase in the return cycle that was thought to be due to abnormal refractoriness of the perinodal fibers.

Duplication of aortic wall seen by echocardiography.

In four patients, echocardiography showed duplication of an aortic wall echo. An aortic dissection was present in only one. Other causes for the echocardiographic pattern were abscess in the interventricular septum, mitral stenosis, and dilatation of the noncoronary sinus of Valsalva. Division of the echo from the mitral ring into two separate posterior aortic wall echoes was seen only in the patient with dissecting aneurysm; it is suggested that this appearance adds to the specificity of the finding of aortic wall duplication by echocardiography in the diagnosis of aortic dissection.

Localization of aortic valve vegetations by echocardiography.

Nine patients with anatomically documented vegetations on one or more cusps of the aortic valve had echocardiograms in which abnormal echoes were associated with the aortic leaflet echoes. The motion of the abnormal echoes during systole correlated well with the anatomic location of vegetations: a vegetation on the right coronary cusp moved anteriorly with systole while a vegetation on the noncoronary cusp moved posteriorly during systole. Our data, although inconclusive, suggest that echoes from a vegetation on the left coronary cusp maintain a mid-aortic position throughout the cardiac cycle. The echocardiographic appearance of vegetations is not specific, but in the setting of septicemia, dense mobile echoes in the region of the aortic valve are strongly suggestive of vegetation. A normal echocardiographic appearance of the aortic valve does not exclude the possibility that vegetation is present, especially if the growth is less than 5 mm in size.

Disposition kinetics of quinidine.

The disposition kinetics of quinidine in 12 hospitalized patients in whom oral quinidine therapy was to be initiated is described. Quinidine in doses of 2.6 to 5.2 mg/kg base were infused intravenously over 22 min. Plasma samples were collected during the postinfusion for 24 hr and analyzed by a specific and sensitive assay procedure. In the 12 hr after administration, postinfusion plasma quinidine concentration decay was described by a biexponential equation. Attempts to include the 24-hr data point in the fitting procedures resulted in poorer agreements between the theoretical and experimental curves. A 2-compartment open model is proposed to describe the disposition of quinidine. The volume of the central pool (Vc) and steady-state volume of distribution (Vdss) were 0.91 +/- 0.11 L/kg and 3.03 +/- 0.25 L/kg, respectively, and indicate that quinidine distribution is predominantly extravascular. Quinidine distribution was quite rapid (t1/2alpha = 7.19 +/- 0.70 min), while the apparent elimination half-life (t1/2beta) was considerably longer, 6.333 +/- 0.47 hr. Total body plasma clearance ranged from 1.49 to 7.15 ml/min/kg (mean 4.70) and is primarily associated with nonrenal mechanisms of drug elimination. Urine specimens collected for 48 hr indicated that 17% of the dose is excreted intact and that urinary excretion was essentially complete within 24 hr. Renal clearance (Clr) was 0.80 +/- 0.18 ml/min/kg. The study demonstrated that there is substantial interpatient variability with respect to quinidine disposition.