Comparison of echocardiographic assessment of cardiac hemodynamics in the intensive care unit with right-sided cardiac catheterization.

Estimation of left ventricular filling pressure and cardiac index is important in the management of patients requiring right heart catheterization. Doppler echocardiography can provide a noninvasive measure of these parameters, but its accuracy in individual measurements, predicting hemodynamic subgroups, and in tracking serial changes in critically ill patients remains to be elucidated. Left ventricular filling pressure and cardiac index were assessed in 49 critically ill patients requiring right heart catheterization and Doppler echocardiographic studies. Two or more serial studies were performed in 18 of these subjects. Patients were placed into 1 of 4 hemodynamic subgroups for each technique based on the acquired hemodynamic parameters. Left ventricular filling pressure and cardiac index by Doppler echocardiography and right heart catheterization were similar (21 +/- 8 vs 20 +/- 8 mm Hg; 3.0 +/- 1.2 vs 2.9 +/- 1.2 L/min/m2, respectively) and correlated well with each other (left ventricular filling pressure, r = 0.88; cardiac index, r = 0.92). The Doppler technique accurately placed 73 of 76 studies into the correct hemodynamic subgroup. The noninvasive technique also reliably tracked serial hemodynamic measurements. We conclude that Doppler echocardiography accurately assesses left heart hemodynamics in critically ill patients. Since this technique can be readily acquired, it can be ideal for the rapid assessment of hemodynamic parameters in critically ill patients, especially when right heart catheterization is delayed or is problematic.

Does cocaine cause coronary vasospasm in chronic cocaine abusers? A study of coronary and systemic hemodynamics.

The pathogenesis of acute myocardial ischemia or infarction following cocaine abuse is not known. Cocaine causes an increase in circulating catecholamines. Therefore alpha-adrenergic mediated focal or generalized coronary artery spasm has been presumed to be the likely mechanism to induce ischemia. However, coronary vasospasm in chronic cocaine abusers has not been demonstrated angiographically. Moreover, it has been observed that patients commonly manifest ischemic changes hours up to a week after abusing cocaine. In order to evaluate direct effects of cocaine on coronary vasculature, 6 chronic cocaine abusers admitted with prolonged chest pain and electrocardiographic ST- and T-wave changes were studied. Cocaine administered intravenously (maximum 32 mg) produced subjective sensation of central nervous stimulation (the "high") in all patients. However there was no significant change in coronary artery diameter (assessed by computer-assisted quantitative technique), myocardial perfusion (assessed by contrast echocardiography) or left ventricular wall motion (assessed by two-dimensional echocardiography) as compared with the baseline values. Coronary sinus flow (thermodilution) showed an upward trend, a probable reflection of a significant increase in cardiac output (average 62%, p less than 0.007). Despite a significant elevation in heart rate (average 56%, p less than 0.007), mean systemic arterial pressure (average 12%, p less than 0.05) and rate-pressure product (average 69%, p less than 0.005), no symptomatic or acute electrocardiographic changes were observed. It is concluded that recreational doses of cocaine do not cause focal or generalized coronary vasospasm or reduced myocardial perfusion in patients who present with chest pain temporally related to cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)

Cocaine-associated chest pain.

STUDY OBJECTIVES: To describe the clinical and ECG features of cocaine abusers evaluated in the emergency department and admitted to the medical coronary care unit with chest pain consistent with myocardial ischemia. DESIGN: A four-month retrospective review of all cocaine abusers who presented to the ED with chest pain and a diagnosis of possible myocardial infarction. SETTING: Urban county hospital. TYPE OF PARTICIPANTS: Forty-eight adult cocaine abusers admitted with chest pain. MEASUREMENTS AND MAIN RESULTS: Patients included 34 men and 14 women with a mean age of 29 +/- 7.3 years. The average duration of cocaine abuse in 28 patients for whom it was reported was 5 +/- 4.8 years. Chest pain occurred within one hour of cocaine abuse in 13 admissions (27%), more than one hour after abuse in 13 admissions (27%), and it was not recorded in 23 admissions (47%). Initial ECGs were evaluated in all patients and revealed significant repolarization abnormalities consisting of abnormal ST segment elevations in 18 (37%) and T-wave inversions in 20 (41%) that often persisted on subsequent ECGs. Three patients sustained acute myocardial infarctions. CONCLUSIONS: Our findings confirm a small but significant incidence of myocardial infarction in cocaine abusers presenting to the ED with chest pain. The chronicity of cocaine abuse, the persistence of ECG abnormalities, and the variable temporal relationship of chest pain to cocaine abuse suggest possible chronic myocardial changes as etiologies of ischemia.

Effect of 5-hydroxytryptamine blockade with ketanserin on myocardial uptake of epinephrine and norepinephrine in patients with congestive heart failure.

Serotonin (5-hydroxytryptamine) has multiple cardiovascular actions. The presence of serotonin in the heart suggests it may be an endogenous source of inotropic support during physiologic or pathologic stress. Serotonin may increase cardiac contractility by augmenting release of norepinephrine at sympathetic nerve endings. Norepinephrine release is markedly elevated in patients with heart failure. To explore the role of serotonin in enhancing norepinephrine release in patients with heart failure, ketanserin, a specific serotonin antagonist, was used as a physiologic tool to examine the effect on transmyocardial norepinephrine flux. Ketanserin (10 mg bolus, 4 mg/hr infusion for +/- 40 min) was administered intravenously to nine patients with congestive heart failure (NYHA III or IV) secondary to congestive cardiomyopathy (N = 7), or ischemic heart disease (N = 2). Plasma catecholamines (norepinephrine, epinephrine, dopamine) were measured in the aorta (Ao) and the coronary sinus (CS) of patients at rest and during supine leg exercise before and after administration of ketanserin. Baseline norepinephrine levels were markedly elevated at rest and during exercise in all patients. Norepinephrine levels were significantly higher in the CS than in the Ao (rest, CS 1185 +/- 235, Ao 878 +/- 381 pg/mL, P less than .05; exercise, CS 2239 +/- 697, Ao 1453 +/- 697 pg/mL, P less than .05). Baseline epinephrine levels were within normal limits. In contrast to norepinephrine levels, epinephrine levels were consistently higher in the Ao than in the CS, indicating unimpaired extraction or uptake across the heart. The relationship between norepinephrine and epinephrine concentration in the Ao and CS suggested a net overflow of norepinephrine in the CS.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute hemodynamic and neurohumoral effects of pindolol: a beta-adrenoceptor antagonist with high intrinsic sympathomimetic activity in patients with dilated cardiomyopathy.

It has been claimed that beta-adrenoceptor antagonists produce clinical improvement and increase longevity in patients with idiopathic dilated cardiomyopathy. Dilated heart is critically dependent upon adrenergic support to maintain forward output. Acute withdrawal of such support, even with small doses of beta-blockers, may worsen myocardial function sufficiently to limit their widespread use. Pindolol (P), a potent beta-adrenoceptor antagonist, possesses high intrinsic sympathomimetic activity. Administration of P to patients with dilated cardiomyopathy may protect against the effects of high circulating catecholamines and at the same time partially maintain intrinsic left ventricular function. We examined the acute hemodynamic effects of P (2.5 mg orally) in seven patients with dilated cardiomyopathy (average ejection fraction, 23%) and resting tachycardia (average, 111 beats/min). As compared to baseline values, P produced a highly significant fall in heart rate (rest, 19%, p less than 0.001; exercise, 24%, p less than 0.01), cardiac output (rest, 20%, p less than 0.01; exercise, 25%, p less than 0.001), and systemic arterial pressure (exercise only, 13%, p less than 0.05). Calculated systemic vascular resistance increased significantly at rest (17%, p less than 0.05). Pulmonary artery pressures did not change. Compared to normal subjects, baseline norepinephrine levels were markedly elevated in patients with dilated cardiomyopathy at rest and during exercise. Pindolol produced a further significant increase in norepinephrine levels. Two of seven patients became appreciably short of breath after P. Despite its substantial intrinsic sympathomimetic activity, pindolol, like other beta-adrenoreceptor antagonists, produces significant hemodynamic impairment in patients with congestive cardiomyopathy. An exaggerated norepinephrine response after the drug may, by increasing peripheral vascular resistance, lead to further deterioration in left ventricular performance.

Hemodynamic and neurohumoral effects of ketanserin, a 5-HT2 receptor antagonist in patients with congestive heart failure.

Ketanserin, a recently developed 5-HT2 receptor antagonist, competitively and selectively blocks the vasoconstrictor activity of 5-hydroxytryptamine (serotonin). We explored a possible contribution of serotonin to augmented vascular tone in patients with severe heart failure, using intravenous and oral formulations of ketanserin. When administered intravenously (10 mg bolus, 4 mg/hr infusion for +/- 40 min) to 10 patients with congestive heart failure (NYHA III or IV) secondary to congestive cardiomyopathy (n = 8) or ischemic heart disease (n = 2), the drug produced a significant increase in cardiac output (rest 24%, p less than 0.001; exercise 19%, p less than 0.01) which was accompanied by a fall in systemic arterial pressure (rest 7%, p less than 0.001; exercise 10%, p less than 0.05) and pulmonary wedge (rest 17%, p less than 0.05; exercise 23%, p less than 0.001) pressure. Calculated systemic vascular resistance (SVR, rest 27%, p less than 0.001; exercise 23%, p less than 0.05) decreased significantly. No significant hemodynamic changes were observed when 40 mg of ketanserin was administered orally to the same group of patients. Plasma catecholamines (norepinephrine, NEP:epinephrine, EP:dopamine) were measured before and after ketanserin at rest and during exercise. Baseline NEP levels were markedly elevated at rest and during exercise in all patients (rest: 878 +/- 381 ng/mL, exercise: 1453 +/- 697 ng/mL). Baseline EP levels were within normal limits. Ketanserin did not produce any change in catecholamine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Favorable effects of pindolol in dilated cardiomyopathy.

We describe the clinical course of a patient with tachycardia at rest, biopsy proven dilated cardiomyopathy, and moderately severe left ventricular systolic dysfunction. Short-term use of pindolol produced a significant fall in heart rate and cardiac output at rest and during exercise. However, after addition of pindolol to the patient's previous regimen of digoxin and furosemide, he made a rapid clinical recovery and has maintained clinical improvement during the last four years of follow-up. The pattern of clinical response suggests that pindolol may have contributed substantially to this patient's recovery.

Hemodynamic effects of nifedipine in acute myocardial infarction with observations on infarct size.

To assess the safety of the slow calcium-channel blocker nifedipine in patients with acutely evolving myocardial infarction, hemodynamic effects of the drug were studied in 12 patients and infarct size was determined by enzymatic method in 14 patients presenting within 12 h of onset of pain. Nifedipine (3 doses of 20 mg given sublingually at 8-h intervals) produced a significant increase in heart rate and cardiac output accompanied by a fall in systemic arterial pressure and vascular resistance. These effects were sustained for a 24-h period of study. Despite an increase in heart rate and cardiac output, there was no worsening of symptoms or electrocardiographic evidence of myocardial ischemia. Assessment of infarct size did not reveal any differences between the control group and the patients who received nifedipine. We conclude that nifedipine may be safely given to patients with acute myocardial infarction. The drug may be usefully employed in patients with acute myocardial infarction accompanied by angina or hypertension.

Acute hemodynamic effects of nifedipine in patients with ischemic heart disease.

We studied the acute hemodynamic effects of nifedipine in 20 patients with angiographically proved coronary artery disease. Eight patients were studied during exercise-induced pain. There was an expected abnormal increase in pulmonary wedge pressure (28 +/- 8 mm Hg, mean +/- SD) accompanying chest pain (onset 179 seconds, duration 334 seconds) and ST-segment depression (2.2 +/- 0.9 mm) on the ECG. Pacing stress was used in six patients and increased left ventricular (LV) end-diastolic pressure (from 16 +/- 6 to 26 +/- 6 mm Hg), volumes (end-diastolic 63 +/- 20 to 81 +/- 22 ml/m2, end-systolic 26 +/- 15 to 47 +/- 16 ml/m2) and impaired ejection fraction (0.60 +/- 0.15 to 0.44 +/- 0.11) compared with control values. In both groups, nifedipine, 20 mg sublingually, significantly shortened duration of pain, reduced ST depression on the ECG (p less than 0.001) and reversed all hemodynamic abnormalities. In another group of six patients with recent (less than 4 months) acute myocardial infarction and moderately severe LV dysfunction at rest, nifedipine reduced LV end-diastolic pressure from 21 +/- 6 to 12 +/- 5 mm Hg and volumes (end-diastolic from 109 +/- 35 to 95 +/- 32 ml/m2, end-systolic from 41 +/- 15 to 31 +/- 7 ml/m2), while the ejection fraction improved significantly, from 0.43 +/- 0.08 to 0.58 +/- 0.11. Thus, the antianginal effect of nifedipine is associated with improved systolic emptying and reduced diastolic filling of the heart. Nifedipine appears to have no discernible adverse effects in patients with depressed LV function.

Clinical significance of exercise-induced ST segment elevation. Correlative angiographic study in patients with ischaemic heart disease.

We have examined the relation between electrocardiographic ST elevation during treadmill exercise (greater than or equal to 1 mm, using the conventional 12 leads), the severity of coronary artery disease, and left ventricular wall motion abnormalities in 680 patients. They were divided into three groups: (1) 218 patients with clinically significant coronary artery disease, (2) 178 patients with clinically significant coronary artery disease, and (3) 284 patients with clinically significant coronary artery disease and previous myocardial infarction. ST elevation during exercise (predominantly in lead V2) was seen in two patients (1%) in group 1, three patients (2%) in group 2, and 147 patients (52%) in group 3. Coronary artery disease (number of vessels involved and severity of stenoses) was comparable in groups 2 and 3. All the patients in group 1 showed a normal left ventricular contraction pattern; 64% of the patients in group 2 showed wall motion abnormalities (predominantly hypokinesia) and 95% of group 3 (mainly akinesia, dyskinesia, or aneurysm). A strongly positive correlation was seen between the ST elevation and left ventricular dysfunction in patients belonging to group 3. The overall sensitivity and the specificity of the stress test in detecting wall motion abnormalities was 55% and 100% respectively. The sensitivity increased with deterioration in left ventricular function, reaching 81% and 90% in patients with dyskinesia and aneurysm, respectively. Maximal ST elevation (greater than or equal to 3 mm) was confined to the patients with dyskinesia or aneurysm. The incidence of ST elevation during exercise was also related to the location of previous infarction, showing a positive response in 85% of patients with anterior myocardial infarction and in only 33% with inferior myocardial infarction. We conclude that ST segment elevation during exercise in patients with previous myocardial infarction is a sensitive and a specific indicator of advanced left ventricular asynergy. The ST segment response during exercise in patients with previous infarction and with angiographically demonstrated myocardial asynergy appears to be a continuous spectrum. A normal ST segment response or elevation alone usually signifies involvement of only one vessel supplying the infarcted myocardium, ST elevation with concomitant ST depression indicates additional coronary artery disease, and ST depression alone indicates overwhelming myocardial ischaemia resulting from multiple vessel disease. The employment of multiple leads is essential to obtain this information.

Clinical evaluation of His-bundle electrogram recorded from the body surface.

A noninvasive method of recording His-bundle activity was developed in our laboratory. This technique is based on the principle of high-gain amplification of the external signals, use of appropriate filters to eliminate random noise, and averaging of the amplified signals over 200-500 cardiac cycles to improve the signal-to-noise ratio. Using this technique we were able to demonstrate external His-bundle activity and to measure the extent His-bundle-ventricular (H-V) interval in 29 of 51 (60%) patients referred to our unit for evaluation of conduction abnormalities or history of collapse. The external technique was validated by the intracardiac electrode method. External H-V interval was reproducible when tested i eight normal subjects and four patients of variation was 4.5% for external H-V interval of 30-90 ms duration). Failure to obtain distinct external His-bundle deflection was largely due to contamination with atrial or ventricular noise. Analysis of all the records showed that the demonstration of external His-bundle activity was directly proportional to the length of the PR segment. The external H-V interval could be measured in all patients with PR segments longer than 100 ms but in less than half in whom the PR segment was shorter than 55 ms. We conclude that the noninvasive technique of recording His-bundle activity is simple and reproducible and can be used at the bedside. It possesses a distinct advantage over the intracardiac technique in that it can be employed in sequential studies. However, in its present state of development, its use is mainly confined to the analysis of conduction disturbances.

Left ventricular aneurysm: pre- and postoperative haemodynamic studies at rest and during exercise.

We studied 9 men with antero-apical left ventricular aneurysms. All suffered from incapacitating angina pectoris without heart failure. Aneurysmectomy was done in 4 patients as the sole procedure while it was combined with revascularisation of the residual myocardium in the other 5. Haemodynamic measurements were made at rest and during submaximal supine-leg exercise before and approximately 6 mth after operation in each patient. Compared to the preoperative levels, we observed a significant increase in respiratory rate at rest (P less than 0.001) and during exercise (P less than 0.01), in ventilation during exercise (P less than 0.05), in mean pulmonary arterial pressure at rest (P less than 0.001) and during exercise (P less than 0.01) and in mean pulmonary wedge pressure during exercise (P less than 0.01). These changes were accompanied by a significant reduction in cardiac output during exercise (P less than 0.01) and in stroke volume at rest (P less than 0.05) and during exercise (P less than 0.01). Heart rate and blood pressure remained essentially unchanged. . The curve representing the relationship between the left ventricular stroke work and the filling pressure shifted downwards and to the right after operation compared to that before operation. Patients who show only minimal haemodynamic disturbances associated with an aneurysm, maintain an effective forward stroke volume by an augmented fibre-shortening of the residual myocardium as well as an increase in the diastolic volume of the heart. Results of our study demonstrated that the compensatory ventricular dilatation may be critical in this group of patients. Despite an increase in average ejection fraction after operation, the removal of the aneurysm led to considerable haemodynamic deterioration in all the patients studied.

Dynamic myocardial scintigraphy with 123I-labeled free fatty acids in patients with myocardial infarction.

We have already shown that myocardial imaging properties of radio-iodinated long-chain free fatty acids (123I-FFA) and thallium 201 (201TI) are comparable in detecting areas of inadequate myocardial perfusion (van der Wall et al. 1980). Besides confirming our earlier observations, the present study tests the potential of 123I-FFA, hexadecenoic acid (123I-16-ha), and heptadecanoic acid (123I-17-H degree A), in assessing regional myocardial metabolism in 30 patients within a week of proven myocardial infarction. The clearance rates (t1/2) of FFA were estimated from mono-exponential time-activity curves, obtained by external detection over infarcted and normally perfused areas during a 30-min period after IV administration of 3-5 mCi 123I-16-HA or 123I-17-H degree A. Six normal subjects served as controls. The t1/2 values in the infarcted areas were found to be significantly lower (18.5 +/- 2.1 min; mean +/- SD, with 123I-16-HA and 16.8 +/- 3.5 min with 123I-17-H degree A) than in non-infarcted areas (34.0 +/- 8.4 min with 123I-16-HA and 34.8 +/- 7.7 with 123I-17-H degree A). The t1/2 values in the control group (27.5 +/- 3.0 min with 123I-17-H degree A) were not significantly different from values found in non-infacted areas in the patient group. Our findings of faster FFA turn-over rates in infarcted tissue are in contrast to previous studies, which have shown prolonged turn-over rates in reversibly ischaemic myocardiu. We conclude that the study of turn-over rates of FFA provides a means to distinguish normally perfused, reversibly ischaemic and irreversibly ischaemic myocardium.

Pharmacokinetics of atenolol and its clinical consequences in patients with angina pectoris.

Pharmacokinetics and clinical effects of daily oral doses of 100 mg and 200 mg atenolol, respectively, were studied in patients with angina pectoris by means of a double-blind cross-over randomized study. Half-lives and areas under the curve were of the same magnitude as described earlier for healthy volunteers and hypertensive patients. However, a steady state level was built up during 4-week medication of 100 mg or 200 mg atenolol daily. Intra-patient correlations of plasma levels and reductions in exercising heart rate were moderate (r = 0.56-0.85). Only plasma levels and exercising heart rates revealed significant differences after a 100 mg and 200 mg dose. These findings, together with the remaining clinical observations, demonstrated that a single daily dose of 100 mg atenolol is useful in patients with exercise-induced angina pectoris.

Clinical, electrocardiographic, and hemodynamic effects of ICI 89,406, a new cardioselective beta-adrenoceptor antagonist with intrinsic sympathomimetic activity, in patients with angina pectoris.

ICI 89,406, a new cardioselective beta-adrenoceptor antagonist possessing marked intrinsic sympathomimetic activity, was administered (0.04 mg/kg, i.v.) to 10 patients with stable, uncomplicated, exercise-induced angina pectoris and angiographically proven coronary artery disease. The drug resulted in a significant reduction in heart rate (from 125 +/- 5 to 110 +/- 4/min, p less than 0.001), mean systemic arterial pressure (from 147 +/- 4 to 137 +/- 3 mm Hg, p less than 0.01), and electrocardiographic ST-segment depression (from 1.9 +/- 0.5 to 0.8 +/- 0.3 mm, p less than 0.01) without any change in pulmonary arterial or wedge pressure during submaximal supine leg exercise on a bicycle ergometer. These changes were accompanied by a reduction of cardiac output in 6/10 patients and of the duration of pain in 8/10 patients. At rest, all the hemodynamic parameters remained essentially unchanged in comparison with the control study. These studies indicate that ICI 89,406 produces effective beta-adrenoceptor blockade during exercise in patients with angina pectoris. The partial agonist activity of the drug may be responsible for the minimal circulatory response at rest.

Haemodynamic effects of terbutaline in chronic obstructive airways disease.

Terbutaline, a cardioselective beta-adrenoceptor agonist, administered intravenously (250 micrograms) to seven patients with chronic obstructive airways disease (mean FEV1 0.99 l) resulted in reduction of mean pulmonary artery pressure (resting 23 +/- 2 to 19 +/- 2 mmHg, p < 0.05; exercise 43 +/- 3 to 35 +/- 3 mmHg, p < 0.05) and calculated pulmonary vascular resistance (resting 168 +/- 27 to 109 +/- 17 dyne s cm-5, p < 0.01; exercise 170 +/- 30 to 119 +/- 18 dyne s cm-5, p < 0.01) accompanied by an increase in heart rate (resting 86 +/- 5 to 96 +/- 4 per min, p < 0.01; exercise 108 +/- 2 to 114 +/- 2 per min, p < 0.01) and cardiac output (resting 3.7 +/- 0.4 to 4.1 +/- 0.4, p < 0.05; exercise 4.9 +/- 0.06 to 6.1 +/- 6 l, min-1 m-2, p < 0.05). The haemodynamic changes were associated with an increase in resting peak expiratory flow rate (184 +/- 20 to 216 +/- 25 l/min, p < 0.01), while the calculated indices of ventilation/perfusion relationship remained essentially unchanged. The reduction in mean pulmonary artery pressure after terbutaline observed in the present studies was probably the result of a combination of simple vasodilator effect, the reduction in airways resistance, and increase in the ventilation.