Charles R. Tucker

Clinical pharmacology and antiarrhythmic efficacy of encainide in patients with chronic ventricular arrhythmias.

We determined the pharmacokinetics, efficacy and therapeutic plasma concentration of encainide, a new antiarrhythmic drug that affects His-Purkinje conduction but not ventricular refractoriness. Nine patients with frequent and complex premature ventricular complexes were studied in a 3-day double-blind protocol. Each day, each patient received 75 mg of i.v. or oral encainide or placebo. Frequent blood samples for encainide plasma concentration determination and continuous ambulatory ECGs were obtained. There was a marked intersubject variation in bloavailability (mean 42 ± 24%, range 7.4-82%), clearance (13.2 ± 5.6 mI/min/kg, range 3.75-22.1 ml/min/kg) and half-life (3.4 ± 1.7 hours i.v., 2.5 ± 0.8 hours oral). Eight of nine patients had more than 90% suppression of premature ventricular complexes for 3-36 hours. Minimal antiarrhythmic plasma concentration was higher (39 ± 54 ng/ml, range 3.5-170 ng/ml) after i.v. dosing than after oral dosing (14 ± 16 ng/ml, range 1.5-48 ng/ml), suggesting an active metabolite after oral dosing in many patients. Minimal side effects were seen despite high peak plasma concentrations (range 794-1556 ng/ml i.v., 36-495 ng/ml oral). The minimal ratio of toxic to therapeutic plasma concentration ranged from 4.3-326 (median 23) after oral dosing. Antiarrhythmic action was associated with an 11-44% widening of the QRS complex that was not associated with other adverse effects. We conclude that encainide effectively suppresses ventricular arrhythmias. Despite a variable bioavailability, high clearance and short half-life, its wide ratio of toxic to therapeutic concentration and probable active metabolite permit a long duration of action, which should allow a reasonable dose schedule in most patients during chronic oral dosing.

The use of echocardiography in diagnosing culture-negative endocarditis.

We reviewed M-mode and two-dimensional echocardiographic findings in 11 patients with abacteremic endocarditis to study the application of echocardiography in this setting. All patients had negative blood cultures but underwent surgery that confirmed the presence of active infective endocarditis. The infection involved native valves in five patients and prosthetic valves in six patients. Valvular masses were identified in eight patients. The other three patients, who had prosthetic aortic valves, had diastolic mitral valve vibration characteristic of aortic regurgitation. One of these three also showed dehiscence of the prosthesis.Three patients had poorly defined clinical illnesses and echocardiography was a prime element in the diagnosis because valvular masses were identified. The operation was facilitated by knowledge of the mass indicated by echocardiography in these eight cases. Also, the surgical approach was affected by knowledge of dehiscence and perivalvular abscess formation in two cases each.

Two-dimensional echocardiographic analysis of segmental left ventricular wall motion before and after coronary artery bypass surgery.

Twenty patients with coronary artery disease were studied with two-dimensional echocardiography the day before saphenous vein bypass graft surgery. Serial studies were obtained 7.4 +/- 2.5 (+/- SD) and 43.4 +/- 13.1 days postoperatively to qualitatively assess the effect of bypass surgery on regional wall motion. Changes in segmental wall motion were assessed semiquantitatively by assigning a segmental wall motion score to each of nine echocardiographically defined segments. Preoperatively, 18% of the segments moved abnormally. The mean overall segmental wall motion score did not change significantly, as shown by comparing the postoperative studies with the preoperative study. However, there was a significant worsening in the septal motion (apical and basal) and a significant improvement in posterior wall motion (apical and basal) after bypass surgery. Anterior and lateral wall motion were not significantly changed. Nonseptal segments that were normal preoperatively usually remained normal; abnormal nonseptal segments usually improved or were unchanged by surgery. The motion of septal segments, however, generally worsened postoperatively whether they were normal or abnormal preoperatively. We conclude that segmental wall motion assessed by two-dimensional echocardiography may improve after revascularization surgery, but the interventricular septum shows impaired motion. This effect of coronary artery bypass on wall motion is better demonstrated relatively late after operation than early in the postoperative course, as has been done in some previous studies.

Echocardiography: M-Mode and Two-Dimensional Methods

We review the basic similarities and differences of currently used M-mode and two-dimensional (2D) echocardiography. Discrete categories of disease are used to show the relative strengths of M-mode and 2D methods. The format of 2D echocardiography is well suited to analyze congenital heart disease, consequences of coronary artery disease, and distortions of anatomy due to acquired heart disease. Rapid structure movement is preserved with M-mode recording, facilitating detailed analysis of motion. The vast clinical experience with M-mode echocardiography can now be augmented by 2D echocardiography, but combination of 2D and M-mode methods is optimal for understanding each type of ultrasound recording and for best serving the patient.

Acute hemodynamic effects of intravenous encainide in patients with heart disease

Encainide, a new antiarrhythmic drug, was given intravenously (0.9 mg/kg) to 18 patients over 15 minutes to evaluate the hemodynamic effects. Hemodynamics and drug plasma concentrations were measured during and 30 minutes postdrug infusions. Encainide infusion was associated with a decrease in cardiac index from 2.6 +/- 0.7 to 2.4 +/- 0.7 L/min/m2 (p less than .05), a significant decrease in stroke work index and left ventricular end-diastolic pressure, and with a rise in systemic vascular resistance. There was no change in systemic or pulmonary arterial pressure, left ventricular dp/dt, or pulmonary vascular resistance. The patients were studied 30 to 60 minutes after cardiac angiography. Comparison of hemodynamic values obtained preangiography with those obtained postangiography (before, during, and after drug infusion) strongly suggests that many of the observed effects were due to radiographic contrast media (initial osmotic volume loading and subsequent diuresis). We conclude that if encainide has any significant hemodynamic effects after intravenous use, it is a modest decrease in cardiac output, possibly as a result of decreased left ventricular filling pressure.

ECHOCARDIOGRAPHIC (ECHO) ASSESSMENT OF COR-PULMONALE IN PATIENTS (PTS) WITH CYSTIC FIBROSIS (CF)

The early clinical recognition and assessment of cor-pulmonale in CF pts is frequently difficult. Echo measurement of right ventricular characteristics may offer a noninvasive, portable means of quantifying cardiovascular changes in CF. Thirty CF pts aged 8 to 26 yrs. (mean 16.7:body surface area≥1M2) from the out-patient and ward service were studied. Clinical score (Shwachman and Kulczyki), standard pulmonary function tests, arterial blood gases and Echo were performed. The mean clinical score for the group was 54 (range 15-100), vital capacity (VC) 62% of predicted (25-108), residual volume (RV) 268% of predicted (55-520), functional residual capacity (FRC) 159% of predicted (72-269), forced expiratory volume (FEV1) 41% of predicted (8-105), mid-maximum expiratory flow rate (MMEFR) 21% of predicted (4-95) and PaO2 57 mmHg (30-83). There was a significant relationship between increase in Echo right ventricular diastolic dimension (RVDD), and (a) decreasing clinical score (p < .01), FEV1 (p<.01) and MMEFR (p<.01) and (b) increasing RV and FRC (p<.01). No significant correlation was noted between RVDD and PaO2. Interventricular septal reversal was present only in pts with severe lung disease. We conclude that changes in RVDD are related to the severity of the lung disease and reflect right heart involvement in CF.

LEFT VENTRICULAR DYSFUNCTION IN PATIENTS WITH CYSTIC FIBROSIS

To evaluate the possibility of left ventricular(LV)dysfunction in patients(pts) with cystic fibrosis(CF), we studied 80 ambulatory and hospitalized CF pts with a mean Shwachman-Kulczyki clinical score of 55(range 15-100)using standard pulmonary function tests, echocardiography (ECHO) and systolic time intervals (STI). ECHO measurements were made of LV internal dimensions at end-diastole(ED) and end-systole, LV posterior wall thickness(PWT) and septal thickness(ST). All values were indexed by body surface area. LV-ED volume (LVEDV) and LV ejection fraction(EF) were calculated. We observed an increase in PWT which was directly related to a decrease in clinical score(p<.0l) and mid-maximal expiratory flow rate (p< .05) and increased functional residual capacity (FRC)(p<.05). EF decreased significantly with increased FFC(p<.05). LV-EDV decreased with increased residual volume (RV)(p<.05) and total lung capacity(p<.05). When compared with age-corrected normal values, the ratio of the STIs, pre-ejection period and LV ejection time(PEP/LVET) increased with decreased clinical score(p<.05) and increased RV(p<.01) and FRC(p<.05). PEP/LVET also increased with increased PWT(p<.001), ST(p<.01) and indexed right ventricular dimension by ECHO(p<.001) and with decreased LVEDV(p<.05). These data showing increased PWT and PEP/LVET, and decreased EF suggest LV dysfunction with increasing severity of pulmonary involvement in pts with CF.

THE VECTORCARDIOGRAM (VCG) IN CYSTIC FIBROSIS (CF)

The VCG (Frank system) as an indicator of severity of pulmonary involvement was assessed in 75 patients (pts) with CF. The Shwachman-Kulczycki clinical score(CS), PaO2, right maximum spatial vector(RMSV) and standard pulmonary function tests were performed. The VCG horizontal loops(HL) were classified on the basis of configuration into four groups: normal, mild (increased anterior forces ± small rightward terminal forces), moderate (increased anterior forces with prominent rightward terminal forces or narrow antero-posterior loop) and severe (diminished anterior forces with marked rightward posterior loop displacement). The CS was similar in the normal and mild groups but progressively decreased in the moderate (p<.01) and severe (p<.05) groups. Mean PaO2 for the normal group was 68 mmHg (range 54-76), mild 66 mmHg(57-83), moderate 56 mmHg (48-80)(p<.05) and severe 44 mmHg(30-60)(p<.01). Vital capacity and forced expiratory volumes were significantly lower (p<.01) in the moderate and severe categories when compared to the normal and mild groups. The mean RMSV in the normal group was 0.8 mv(range 0.4-1.1), mild 1.1 mv(0.7-2.2) (p<.02),moderate 1.2 mv(0.7-2.9) (p<101) and in the severe 1.8 mv(0.8-2.7) (p<.01). During the 8 months the study was in progress, 7 pts died all of whom were in the moderate or severe categories, we conclude that there is a significant relationship between right heart involvement assessed by the HL of the VCG and the severity of CF determined by CS, PaO2 and some pulmonary tests.

Structure Identification by Contrast Echocardiography

The exciting technique of structure identification by contrast echocardiography has many developing applications and is now especially useful in defining cardiac chambers and in the recognition of congenital heart defects, as well as of complications of the abnormal flow resulting from such defects. But, if we are trying to define a given chamber, or the time sequence of flow of contrast moving from one chamber to another, the basic identity of each structure is the most important information we must begin with. Most people doing echocardiography now believe they understand cardiac anatomy very well, and in fact they do. But as the equipment has allowed us to see more and more details of the cardiac anatomy, and we are presented a more comprehensive view of the heart than has been possible in the past, the subtle details of anatomic features that were not visible or not important before become crucial to our diagnosis.