Two-dimensional echocardiography in the diagnosis of carcinoid heart disease

Tricuspid valve disease accounts for significant morbidity and mortality in the carcinoid syndrome, but M-mode echocardiography is often insensitive in completely defining the tricuspid valve. We performed two-dimensional echocardiography (2DE) in seven patients with proven carcinoid syndrome. There were five males and two females whose ages ranged from 53 to 79 years. The carcinoid syndrome had been present by symptoms for 12 to 84 months and by 5-HIAA levels for 6 to 84 months prior to 2DE. Short, thickened, immobile tricuspid valve leaflets, fixed in a partially open position, were visualized in two patients and confirmed in one patient at surgery. Tricuspid regurgitation was demonstrated angiographically in one and by contrast 2DE in the other. A third patient had clinical evidence of tricuspid stenosis with a doming tricuspid valve on 2DE. The motion of the tricuspid value viewed in real time was clearly distinct in these two situations. Four patients had both normal M-mode and 2DE studies despite the fact that clinical and biochemical evidence of carcinoid disease had been present for equally long periods of time. The tricuspid valve was best visualized in the parasternal right ventricular long-axis and short-axis views. The apical four-chamber view was less helpful. Thus, 2DE demonstrated specific tricuspid valve abnormalities in the carcinoid syndrome with thickening, shortening, and immobility of the leaflets when valvular regurgitation was present and thickening and doming when the valve was stenotic. 2DE should be a useful method in the diagnosis and sequential evaluation of patients with carcinoid heart disease.     

Comparative influence of ouabain,norepinephrine and heart rate on myocardial oxygen consumption and inotropic state in dogs

The purpose of this study was to compare the myocardial oxygen cost of augmented inotropic state produced by ouabain, norepinephrine, or increased heart rate. This problem was examined in dogs using an isovolumically contracting left ventricular preparation. Inotropic state was measured as the maximum observed contractile element velocity at the lowest common level of wall stress (MAX V). Peak left ventricular wall stress was maintained constant in each dog so that it would not influence changes in myocardial oxygen consumption (MVO₂). Ouabain (4 × 10² μmoles/Kg.) and norepinephrine (2 × 10³ μmoles/Kg./minute) always augmented inotropic state (MAX V) and increased MVO₂. The positive slopes of the regression of MVO₂ on MAX V for ouabain (45.4 ± 12.5 μl/beat/100 Gm./muscle length/sec; mean ± SEM) and norepinephrine (34.5 ± 5.6 μl/beat/100 Gm./muscle length/sec; mean ± SEM) were not significantly different, indicating that for an equal augmentation of inotropic state, ouabain increases myocardial oxygen demands to the same extent as does norepinephrine. When the results with ouabain or norepinephrine were compared to results obtained by altering heart rate, it was found that increasing inotropic state by these pharmacologic agents is more costly in terms of myocardial energy demands than when inotropic state is enhanced by increasing heart rate.     

Echocardiographic classification of complete atrioventricular canal defects

M-mode echocardiographic records of 26 patients with surgically proven complete atrioventricular canal defect were reviewed. Fragmentation of the interventricular septum and anterior displacement of the mitral annulus into the left ventricular outflow tract were noted in all patients. In 25 of 26 a common atrioventricular valve leaflet echo could be identified in the left ventricular outflow tract at the area of the crest of the interventricular septum. Recordings of echographic scans performed in the area of the left ventricle demonstrated separate “mitral” and “tricuspid” contributions to atrioventricular valve echoes in all 13 patients with type A defect, and a single common atrioventricular valve leaflet in 10 of 11 patients with type C complete atrioventricular canal. Two patients with type B defect had findings intermediate between these two patterns. M-mode echocardiography presumptively diagnosed complete atrioventricular canal in all 26 patients and diagnosis was definitive in 25 of 26. In addition, echocardiographic atrioventricular valve patterns permitted anatomic classification in the large majority of cases.     

Congestive heart failure in childhood and adolescence: recognition and management

Clinical, coronary arteriographic, and hemodynamic studies were performed in 55 patients with left bundle branch block (LBBB) and coronary artery disease and were compared with 110 patients consecutively matched for age and sex with ischemic heart disease but without LBBB. No significant differences were found in duration of symptoms or frequency of prior myocardial infarction, hypertension, or diabetes mellitus; however, the LBBB patients had a significantly (p < 0.001) higher frequency of congestive heart failure (38.2% vs 11.8%) and cardiomegaly (63.6% vs 25.5%). An evaluation of severity of the coronary disease on the basis of subtotal vs total obstructive lesions, number of vessels involved, total coronary score, and individual coronary arteries involved revealed no significant differences between the groups. The LBBB patients had significantly (p < 0.001) greater impairment of left ventricular function as reflected by the end-diastolic volume (107 ± 43 vs 79 ± 30 ml/m²), ejection fraction (0.35 ± 0.19 vs 0.59 ± 0.18), and frequency of an abnormal contractile pattern (91% vs 61%). Evaluating the LBBB patients on the basis of the QRS width and axis revealed no significant intragroup differences in clinical profile, severity of coronary disease, or left ventricular dysfunction. A prolonged PR interval (≥0.20 second) was associated with more severe coronary artery disease and an enlarged heart. This study indicates that coronary artery disease associated with LBBB identifies patients with severe left ventricular dysfunction.     

Arterial and coronary sinus catecholamines in the course of spontaneous coronary artery spasm

We studied plasma catecholamine levels in 10 patients with frequent spontaneous episodes of coronary artery spasm to evaluate the role of the sympathetic nervous system. Peripheral venous norepinephrine in supine and upright postures, urinary excretion of catecholamines, and functional testing of the sympathetic nervous system did not differ from the same measurements in control subjects. Arterial and coronary sinus levels of norepinephrine and epinephrine drawn early in ischemia were not elevated over baseline; coronary sinus norepinephrine levels were higher than those in arterial samples and rose from 315 ± 32 (pg/ml ± SE) at the onset of ST elevation to 490 ± 49 pg/ml late in ischemia (p < 0.05). Plasma epinephrine levels, higher in arterial than coronary sinus samples, also rose significantly only late in ischemia, from 44 ± 14 pg/ml to 148 ± 35 pg/ml (p < 0.05) in arterial blood and from 33 ± 10 pg/ml to 108 ± 29 pg/ml in coronary sinus samples (p < 0.05). Generalized sympathetic nervous system activation is not likely to be the sole cause of coronary artery spasm.     

Tocainide therapy for refractory ventricular arrhythmias

Tocainide, a congener of lidocaine, was used to treat symptomatic ventricular arrhythmias in 19 patients resistant to or unable to tolerate conventional agents. In this highly selected group, 15 showed good initial responses to oral therapy. Ventricular tachycardia was suppressed to a greater extent than isolated ventricular ectopic depolarizations at any plasma concentration, and upward dose-ranging showed progressive suppression of both. Arrhythmia responsiveness to lidocaine was found to be an excellent predictor of tocainide response. Of the 15 responders, one died 24 hours after stopping therapy, three died while receiving tocainide, nine stopped because of adverse reactions (five allergic), and two continue on therapy at 1 and 4 years. We conclude that tocainide is an effective agent for the short-term suppression of ventricular arrhythmias, particularly ventricular tachycardia sensitive to lidocaine, but a high incidence of adverse effects limits its application to chronic therapy in many patients.     

Inotropic effects of tolbutamide in man

The hemodynamic responses of normal subjects to intravenous injections of tolbutamide, 250 mg., and 1,000 mg., were assessed by measurements of serial systolic time intervals.Analysis of results, compared to saline control, revealed evidence of minor inotropic effects during the period five to 10 minutes after infusion. Small but statistically significant (p < 0.05) decreases in pre-ejection phase and electromechanical systole were noted. The time response of these changes did not correlate with dose or blood level of tolbutamide, and appeared to coincide with peak insulin levels.No inotropic or chronotropic effects were seen during the first four minutes after infusion, suggesting that the myocardial adenyl cyclasestimulating properties of the drug, previously demonstrated in vitro, are not significant in intact man. The minor late inotropic effects are of doubtful clinical significance, and cannot be invoked to explain the reported increased cardiovascular mortality of patients treated with tolbutamide.     

Regional hemodynamic effects of beta-adrenergic blockade with propranolol in the unanesthetized primate

The effects of equal doses of d- and dl-propranolol on systemic and regional hemodynamics were studied in the unanesthetized rhesus monkey using the radioactive microsphere technique. No changes in systemic hemodynamics were seen with d-propranolol, but dl-propranolol significantly decreased the cardiac output (?25 per cent), heart rate (?18 per cent), and stroke volume (?9 per cent), and increased the total peripheral resistance (+40 per cent). During the dl-propranolol infusion the cardiac output was preferentially distributed to the brain with a small decrease in the fraction received by the liver. Flow to all organs except the brain was diminished during dl-propranolol, and the decrease was proportionate to the change in cardiac output. No change in distribution of flow was seen with d-propranolol and total flow to all organs was unchanged from control, with the exception of an increase in flow to the skin. This comparison of d- and dl-propranolol indicates that the effects of dl-propranolol are due to beta-adrenergic blockade rather than a non-specific effect of the drug.     

Use of droperidol-fentanyl sedation for cardiac catheterization in children

Droperidol-fentanyl sedation for cardiac catheterization was evaluated in 106 consecutive children ≥ two years of age. The dose of 0.025 c.c. per kilogram of body weight (maximum 1 c.c.) produced adequate sedation in all but two patients without producing significant hypoventilation or heart rate changes. In patients without left heart volume overload or myocardial disease, left ventricular volume studies and pressurevelocity indices of contractile state were normal. Side effects were rarely encountered and easily controlled or reversed with diphenhydramine. Although we recommend this combination for cardiac catheterization sedation, we would not recommend exceeding our dosage schedule.     

Malignant ventricular tachyarrhythmias associated with the use of encainide

In patients treated with the antiarrhythmic drug, encainide, the agent appeared to cause or exacerbate malignant ventricular tachyarrhythmias in 11 cases. The most common type of arrhythmia associated with encainide toxicity was polymorphic ventricular tachycardia (VT) resulting in cardiac arrest. In contrast to drug-induced arrhythmias commonly encountered with quinidine and other type I antiarrhythmic drugs, encainide-induced rhythm was not associated with marked QT prolongation, was not necessarlly initiated by R-on-T premature ventricular beats, and usually did not self-terminate. Two patients could not be resuscitated from the rhythm, and several others required prolonged or multiple resuscitations. The risk of encainide-induced ventricular tachyarrhythmias was 11% in 90 patients receiving the drug for recurrent sustained VT and/or fibrillation (VF), 2.2% in 47 patients receiving the drug for chronic complex ventricular ectopic activity. Encainide-induced arrhythmias occurred 29.8 ± 11.3 hours (range 17 to 48 hours) after starting chronic oral maintenance doses or after dose increases, or 1 to 2 hours after single large doses. Patients experiencing this adverse effect could not be distinguished from those who did not on the basis of encainide dose, degree of QRS widening, or clinical status. We recommend that patients with history of sustained VT or VF have encainide therapy started only in a hospital setting with continuous ECG monitoring and capabilities for cardiopulmonary resuscitation. Dose changes should not be made more frequently than every 48 hours, and patients should not be discharged from the hospital until they have been on a stable dose of encainide for a minimum of 48 hours.     

Effect of hypoglycemia on extracellular levels of cyclic AMP in man.

This study was designed to assess the response of cyclic AMP to "endogenous" hormonal stimulation resulting from insulin-induced hypoglycemia. Insulin was administered to four normal subjects and four adrenalectomized patients. Hypoglycemia resulted in four-fold increases in plasma cyclic AMP. This response is thought to be secondary to beta-adrenergic stimulation for the following reasons: (1) the response was absent in adrenalectomized, cortisol-treated subjects; (2) it was abolished by propranolol; and (3) urinary excretion of cyclic AMP did not reflect the rise in plasma cyclic AMP.     

Effects of proximal intra-atrial Wenckebach on distal atrioventricular nodal, and His-Purkinje, block with special reference to the theory of alternating Wenckebach periods

Intra-atrial Wenckebach patterns of stimulus-to-response intervals coexisting with distal, A-V nodal, and His-Purkinje, blocks occurred in eight patients during high right atrial stimulation at rapid rates. In two patients with 2:1 St-H block and in two patients with 4:1 St-V block, an increase in the degree of block occurred when the proximal intra-atrial Wenckebach cycle was completed with the stimulus which otherwise would have been propagated to the distal levels. However, the degree of block did not increase when the intra-atrial Wenckebach terminated in distally blocked stimuli. In one patient progression of 4:1 into 5:1 St-V block was due to the association of intra-atrial Wenckebach with alternating 2:1 block at the A-V nodal, and His-Purkinje, levels. Contrasting with most reports dealing with the mechanisms of alternating Wenckebach in a single structure, this study permitted the determination of the boundaries between proximal and more distal levels. It also showed that alternating Wenckebach cycles (of St-H intervals) ending with two consecutively blocked stimuli could result from the association of proximal intra-atrial Wenckebach with distal, A-V nodal Wenckebach, or abortive AW, cycles. The electrophysiology of documented two, or three, level block in different structures has validated previously made assumptions regarding multilevel block in a single structure.     

Initiation of atrioventricular nodal reentrant tachycardia in patients with discontinuous anterograde atrioventricular nodal conduction curves with and without documented supraventricular tachycardia: Observations on the role of a discontinuous retrograde conduction curve

To evaluate factors playing a role in initiation of atrioventricular (AV) nodal reentrant tachycardia utilizing anterogradely a slow and retrogradely a fast conducting AV nodal pathway, 38 patients having no accessory pathways and showing discontinuous anterograde AV nodal conduction curves during atrial stimulation were studied. Twenty-two patients (group A) underwent an electrophysiologic investigation because of recurrent paroxysmal supraventricular tachycardia (SVT) that had been electrocardiographically documented before the study. Sixteen patients (group B) underwent the study because of a history of palpitations (15 patients) or recurrent ventricular tachycardia (one patient); in none of them had SVT ever been electrocardiographically documented before the investigation. Twenty-one of the 22 patients of group A demonstrated continuous retrograde conduction curves during ventricular stimulation. In 20 tachycardia was initiated by either a single atrial premature beat (18 patients) or by two atrial premature beats. Fifteen of the 16 patients of group B had discontinuous retrograde conduction curves during ventricular stimulation, with a long refractory period of their retrograde fast pathway. Tachycardia was initiated by multiple atrial premature beats in one patient. Thirteen out of the remaining 15 patients received atropine. Thereafter tachycardia could be initiated in three patients by a single atrial premature beat, by two atrial premature beats in one patient, and by incremental atrial pacing in another patient. In the remaining eight patients tachycardia could not be initiated. Our observations indicate that the pattern of ventriculoatrial conduction found during ventricular stimulation is a marker for ease of initiation of AV nodal tachycardia in patients with discontinuous anterograde AV nodal conduction curves.