Hemodynamic effects of inhaled terbutaline in congestive heart failure patients without lung disease: Beneficial cardiotonic and vasodilator beta-agonist properties evaluated by ventricular catheterization and radionuclide angiography

To evaluate the hemodynamic effects of the beta-adrenergic receptor agonist, terbutaline sulfate, when given by inhalation in ventricular dysfunction, 0.5 mg of the agent was given by nebulizer to 13 patients with congestive heart failure (nine coronary heart disease and four with idiopathic cardiomyopathy). Data were obtained before and 10 and 30 minutes post inhalation, by right heart catheterization and by gated equilibrium radionuclide ventriculography. All patients responded with increased cardiac output (3.5 to 4.3 L/min, p < 0.01) and stroke volume (40 to 49 ml, p < 0.01) without change in heart rate. Decreases occurred in peripheral vascular resistance (1924 to 1443 dsc^?5, p < 0.01), left ventricular filling pressure (21 to 15 mm Hg, p < 0.01), and systemic arterial oxygen tension (81 to 72 mm Hg, p < 0.05). Both left and right ventricular ejection fractions rose (0.24 to 0.38 and 0.36 to 0.51, both p < 0.01) with concomitant declines in blventricular end-diastolic volumes. All variables indicated changed rapidly at 10 minutes post inhalation and returned to control levels by 30 minutes after the agent. Thus moderate inhaled doses of terbutaline produce prompt, potent, and transient salutary hemodynamic effects due to its peripheral vasodilator and cardiotonic properties, without untoward arrhythmogenic or anginal provoking influences in the present study.     

Comparison of single-plane and biplane contrast analyses of right ventricular function and size

To evaluate the utility of single and biplane right ventricular (RV) contrast angiograms, we evaluated 25 canine RV casts and 31 cineangiograms performed in patients during standard contrast ventriculograms. Both standard single and biplane formulae were utilized. In the 25 canine RVs, absolute volume was determined by water displacement. Both biplane (r = 0.96) and single-plane (r = 0.86) volumes correlated well with cast data. These formulae were then applied to contrast ventriculograms in the 31 patients (30-degree right anterior oblique and 60-degree left anterior oblique projections). The ejection fractions (EFs) calculated from the single-plane technique provided fair correlation with EFs derived from the biplane data (r = 0.81, y = 0.81X + 0.05). Similar correlations were noted when end-diastolic volume results were compared (r = 0.78, y = 0.57X + 56.4). However, while single-plane contrast right ventriculograms correlate with estimates of global RV function and size by biplane methods, considerable scatter of the data may limit its application in individual cases.     

Radionuclide analysis of ejection time,peak ejection rate,and time to peak ejection rate: Response to supine bicycle exercise in normal subjects and in patients with coronary heart disease

Using equilibrium radionuclide angiography, we evaluated the ejection time (ET), peak ejection rate (PER), and time to peak ejection rate (TTp) at test and during supine bicycle exercise in 39 subjects, divided into three groups: group 1 = 13 normal subjects; group 2 = 10 patients with a previous infarction (MI); and group 3 = 16 patients with coronary disease without a previous MI. Normal subjects had greater ejection fractions and PERs than the other two groups at rest or peak exercise (p < 0.05). PER was no more useful than ejection fraction in identifying cardiac dysfunction at either rest or exercise. The time of its occurrence varied with the group studied, and was slightly but significantly later in systole in groups 2 and 3 when compared to normals (p < 0.05), though substantial overlap between groups occurred. During exercise, absolute ET shortened in all groups, but actually increased as a function of the R-R interval. The time to peak ejection rate (normalized for the R-R interval) was greater in the noninfarct group (group 3) patients (p < 0.05) when compared to the group 1 or group 2 individuals at peak exercise. In conclusion, equilibrium radionuclide angiography is a useful technique for the quantification and characterization of events during systole, and is capable of providing information on the timing of events during ejection. Tardokinesis, or the delay of ventricular ejection, is not seen in the response of global indices of left ventricular function to exercise stress. While global early systolic indexes may not detect regional dyssynchrony, their timing during stress may occasionally aid in discerning the presence of cardiac dysfunction.     

Pulmonary blood volume: relationship to changes in left ventricular end-diastolic pressure during atrial pacing

Little data exist about the relationship between changes in cardiac end-diastolic pressure and changes in pulmonary blood volume. To assess this relationship, we studied 11 patients with coronary heart disease during atrial pacing in an attempt to produce multiple pressure-volume points. During catheterization, we obtained Millar pressure recordings of end-diastolic pressure along with equilibrium radionuclide angiograms. Cardiac output, ejection fraction, and pulmonary blood volume were obtained by means of recently validated radionuclide techniques. During pacing, substantial changes in pulmonary blood volume occurred only with marked increase in end-diastolic pressure volume (greater than or equal to 15 mm Hg) and rarely exceeded 15% of control pulmonary blood volume. Cardiac output did not change, while ejection fraction declined during pacing. There was a fair correlation between the absolute change in pulmonary activity (or pulmonary blood volume) or the percentage of change in pulmonary activity over the control value with end-diastolic pressure when all the data points were evaluated (n = 74, r greater than 0.70). However, the scatter in the data precluded making accurate estimates of pressure changes from changes in radionuclide volume changes. We conclude that large changes in cardiac filling pressure must occur during atrial pacing, where cardiac output does not change, before visible pulmonary blood volume changes occur. This may limit the extrapolation of presumed pressure changes from known pulmonary blood volume when changes are small.     

Response of the left ventricle to stress: Effects of exercise,atrial pacing,afterload stress and drugs

A variety of tests are being utilized today to diagnose the presence of ischemie heart disease, assess the prognosis of myocardial and valvular heart disease and evaluate the effects of various pharmacologic agents on cardiac performance. This review summarizes the current evidence regarding the response of left ventricular performance and size to atrial pacing, afterload stress and various forms of exercise. The response in normal persons and in subjects with coronary heart disease is reviewed and, when applicable, the effects of various pharmacologic agents on exercise performance in these patient groups are examined.     

Radionuclide evaluation of the systolic blood pressure/end-systolic volume relationship: response to pharmacologic agents in patients with coronary artery disease

To assess the response of the relationship between systolic blood pressure and end-systolic volume to pharmacologic agents with known cardiac effects, we studied 21 patients with known coronary heart disease by means of gated radionuclide angiograms during the infusion of phenylephrine. Each individual was studied during the infusion of phenylephrine twice, once as a control and the second time after the administration of either intravenous dobutamine, topical nitroglycerin ointment, or intravenous propranolol. Eight individuals received 10 micrograms/kg/min of dobutamine, which reduced resting cardiac volumes (p less than 0.01), raised ejection fraction (p less than 0.01), and shifted the slope (1.38 +/- 0.50 to 2.03 +/- 0.69, p less than 0.01) and pressure intercept received 2 inches of nitroglycerin ointment. Nitroglycerin increased ejection fraction (p less than 0.05) and reduced volumes (p less than 0.05) but did not alter either the slope (1.46 +/- 0.68 to 1.49 +/- 0.61, p = NS) or intercept (10.6 +/- 5.4 to 10.1 +/- 6.4 mm Hg, p = NS) of the relationship. Eight patients received 15 mg of intravenous propranolol. Propranolol reduced resting ejection fraction (p less than 0.05), increased volumes (p less than 0.05), and reduced both the slope (1.67 +/- 0.58 to 1.51 +/- 0.53, p less than 0.05) and the intercept (13.8 +/- 2.5 to 7.5 +/- 2.3 mm Hg, p less than 0.05) of the pressure-volume relationship. Thus the systolic blood pressure/end-systolic volume relationship can be assessed from radionuclide angiograms.     

Radionuclide analysis of pulmonary blood volume: The response to spontaneous angina pectoris and sublingual nitroglycerin in patients with coronary artery disease

By manually assigning pulmonary regions of interest and deriving pulmonary time-activity (volume) curves, we were able to make count estimates of pulmonary blood volume (PBV) from gated cardiac blood pool scans. Five patients with coronary heart disease developed angina spontaneously while under a gamma camera. This produced an increase in cardiac volumes (p < 0.05), a reduction in left ventricular ejection fraction (p < 0.01), along with a marked increase in PBV (0.010 ± 0.002 to 0.015 ± 0.003 untils, p < 0.05). Nitroglycerin was then administered and reduced PBV in association with a return to normal in cardiac systolic function and size. In patients with stable chronic ischemic heart disease, sublingual nitroglycerin also reduced PBV (p < 0.05), although not as much as when administered during an anginal episode. We conclude that gated imaging of the chest can be utilized to follow changes in PBV serially. These changes can be utilized to evaluate clinically important changes in hemodynamic status and the response to pharmacologic interventions.     

Influence of the pericardium on left ventricular diastolic pressure-volume curves in dogs with sustained volume overload

The pericardium is largely responsible for displacement of the left ventricular diastolic pressure-volume curve observed after acute volume loading in dogs. Likewise the pericardium has been considered likely to play a role in displacement of the curve in patients with acute cardiac failure and in shifts following manipulation of afterload. This study was designed to examine the influence of the pericardium on the diastolic pressure-volume relation of the left ventricle when volume load is more sustained, a setting relevant to observations made in patients with heart failure. We measured left ventricular pressure and volume in six conscious dogs with sustained volume overload (mean left ventricular end-diastolic pressure 21 mm Hg, left ventricular end-diastolic volume 149% of the upper limit of normal for our laboratory) produced by aortocaval shunt created 7 to 29 days earlier. Simultaneous left ventriculograms and pressures were obtained before and during nitroprusside infusion with the pericardium intact and in four dogs the studies were repeated 7 to 15 days after pericardiectomy. In all six dogs with intact pericardium, nitroprusside displaced the entire pressure-volume curve downward whereas after pericardiectomy, the pressure-volume data points obtained before and during nitroprusside infusion fell on a single curve. These results were similar to those previously reported for acute volume overload. Nitroprusside did not alter the time course of left ventricular pressure fall during the isovolumic period of diastole either before pericardiectomy (28.8 +/- 10.2 sec,-1, 28.4 +/- 11.9 sec-1) or after (28.8 +/- 6.7 sec-1, 26.1 +/- 7.2 sec-1). These data indicate that in dogs subjected to volume overload sustained for periods of up to 29 days, the pericardium affects the left ventricular diastolic pressure-volume curve and contributes to the elevation of left ventricular filling pressure through upward displacement of this curve.     

Analysis of ventricular emptying and filling indexes during acute increases in arterial pressure

Using equilibrium radionuclide angiography, an evaluation was made of the response of left ventricular ejection and filling rates at rest and during acute increases in afterload in 8 normal volunteer subjects and 10 patients with previous transmural myocardial infarctions. Using the postatropine point for comparison, normal patients increased ejection time and decreased peak ejection rate (-3.90 +/- 0.49 vol/s to -3.41 +/- 0.95 vol/s) and peak filling rate (3.94 +/- 0.88 vol/s to 3.51 +/- 0.38 vol/s). Infarct patients had similar responses, although all indexes were lower than the corresponding values in the normal subjects. At rest, the ratio of peak filling to emptying rate was similar in the normal subjects and the infarct patients (1.01 +/- 0.24 versus 0.99 +/- 0.25, respectively) and maintained that relationship after atropine (0.91 +/- 0.11 versus 0.81 +/- 0.21) and at the peak increase in arterial pressure (1.07 +/- 0.21 versus 1.02 +/- 0.32). The ratio of time to peak filling/time to peak emptying behaved in similar fashion regardless of the differences in the absolute values. In this study, left ventricular filling and emptying behaved in a similar fashion in response to the alteration in arterial pressure in normal subjects and in patients with previous myocardial infarctions.     

Assessment of right ventricular function at rest and during exercise in patients with coronary heart disease: A new approach using equilibrium radionuclide angiography

To evaluate a new method of calculating right ventricular ejection fraction by equilibrium radionuclide angiography and to assess its response during supine bicycle exercise, 20 normal persons and 50 patients with angiographically documented coronary artery disease were studied. Each subject underwent a resting equilibrium and first pass right ventricular study as well as symptom-limited graded bicycle exercise while supine. The correlation between the two methods in all 70 cases was good (r = 0.81). Inter- and intraobserver variability was small (3.9 ejection fraction units or less) and serial reproducibility (two studies performed 2 weeks apart) was also good (4 ejection fraction units or less). There was no difference in the right ventricular ejection fraction at rest when normal subjects and patients with coronary disease were compared (0.49 ± 0.10 versus 0.46 ± 0.08). Ejection fraction increased with exercise in normal subjects (0.49 ± 0.10 to 0.64 ± 0.12, p < 0.005). As a group, patients with right coronary stenosis (alone or in combination with other lesions) showed no change in ejection fraction with exercise (0.46 ± 0.13 to 0.45 ± 0.12); and ejection fraction increased with exercise in patients with coronary disease without right coronary stenosis (0.46 ± 0.08 to 0.53 ± 0.11, p < 0.05). Among patients with both significant right and left coronary artery disease more severe right ventricular dysfunction during exercise was seen in the presence of more severe left ventricular dysfunction. It is concluded that during exercise the right ventricle shows dysfunction caused in part by local ischemia as well as by altered loading conditions due to left ventricular dysfunction. Equilibrium angiography is a useful and reliable method for evaluating right ventricular function in man.     

The role of the pericardium in interactions between the cardiac chambers

Distension of one side of the heart involves both the strium and the ventricle, and such atrioventricular enlargement encoroaches more on pericardial volume than would ventricular distension alone. The influence of distension of the entire right side of the heart on the pressure-volume relationship of the entire left heart was studied in six postmortem canine hearts with intact pericardium. The pressure-volume relation of the left heart was determined when the right heart was empty and when it was filled with saline. The pressure-volume curve of the left heart became steeper when the volume of the right heart was increased. However, after subtracting pericardial pressure from the left heart pressure, the pressure-volume curves were unaffected by increased volume of the right heart. Selective distension of the entire right heart has a considerable effect on the filling characteristics of the left heart when the pericardium is intact, although this is less than that observed in experiments in which the more compliant atria have been excluded. This effect becomes negligible after subtracting pericardial pressure.     

Creatine kinase isoenzymes in the assessment of heart disease.

Twenty-four patients with severe congestive heart failure and cardiomegaly in whom the presence or absence of significant coronary disease could not be ascertained clinically underwent fluoroscopy for coronary artery calcification prior to cardiac catheterization. Ten of the patients were found to have significant coronary artery disease, and 14 had normal coronary arteriograms. Coronary artery calcification was found in all ten patients with significant coronary disease, and was absent in all of those patients with normal coronary arteriograms. We conclude that fluoroscopy for coronary artery calcification provides a reliable noninvasive method for differentiating ischemic from nonischemic cardiomyopathy.     

The effects of oral propranolol, digoxin and combination therapy on the resting and exercise electrocardiogram.

The effects of propranolol, digoxin and combination therapy (/D) on the resting and exercise ECG were studied in ten normal subjects and 20 patients with coronary artery disease (CAD) given a sequence of oral placebo, propranolol, P/D, digoxin and placebo, for two week periods. Digoxin produced a significant decrease in T-wave amplitude and often resulted in ST segment depression in the resting ECG. Propranolol, digoxin, and P/D tended to decrease the QTc interval and prolong the PR interval. However, CAD patients were more sensitive to PR prolongation than normals while receiving propranolol or digoxin alone. Propranolol therapy did not significantly affect the ST segment of the exercise ECG in the normal subjects or the CAD patients without an ischemic control exercise ECG. By contrast, 50 per cent of the normal subjects developed "false-positive" ischemic ST segment responses to exercise while receiving digoxin of P/D and three of eight CAD patients without ischemic control exercise ST segments had a similar response to digoxin or P/D. In 12 CAD patients with ischemic control exercise ST segments, propranolol did not affect the amount of ST segment depression at the onset of angina or the maximum amount of ST segment depression. Digoxin or P/D both uniformly increased the maximum amount of ST segment depression which was greater with digoxin than P/D. However, the maximum heart rate on P/D was significantly reduced as compared to that on digoxin. It is concluded that (1) CAD patients are more sensitive to propranolol or digoxin-induced AV block than normals, (2) propranolol does not change the magnitude of ischemic exercise ST segment depression, (3) digoxin increases ischemic exercise ST segment depression and results in a high incidence of false-positive exercise tests, and (4) the addition of propranolol to digoxin attenuates the effects of digoxin on the exercise ST segment.     

The isovolumic index: A new noninvasive approach to the assessment of left ventricular function in man

Both a high ratio of preejection period (PEP) to left ventricular ejection time (LVET) and a prolonged isovolumic relaxation time are associated with left ventricular dysfunction. In pilot studies in instrumented dogs, we measured a combined isovolumic index, defined as (isovolumic contraction + isovolumic relaxation time)/LVET and found an inverse correlation with changes in fractional shortening. To test the utility of this index in human subjects, we used the electrocardiogram, mitral valve (MV) echogram, and indirect carotid arterial tracing to calculate isovolumic index as (time from R wave to MV opening — LVET)/LVET × 100%. Normal subjects had isovolumic index values that averaged 24 ± 7% (standard deviation), in contrast to patients with cardiomyopathy who averaged 5 ±14% (p < 0.001 versus normal values) and patients with coronary artery disease who averaged 40 ±15% (p < 0.001 versus normal values and patients with cardiomyopathy). All normal subjects had an isovolumic index of < 32% and all patients with cardiomyopathy had values >32%. Of patients with coronary artery disease, 72% (21 of 29) had an isovolumic index >32%. An isovolumic index >32% identified 20 of 22 patients (91%) with a reduced ejection fraction and 12 of 14 (86% ) with a segmental wall motion abnormality, and it was a more sensitive marker of these abnormalities than abnormal E point-septal separation. In 6 patients with coronary artery disease who had simultaneous echocardiograms and measurements of left ventricular pressure by micromanometer tip catheter, the time constants of isovolumic pressure decrease were uniformly increased in association with an isovolumic index >32%. In contrast, all had normal PEP/LVET ratios. The isovolumic index is thus a sensitive, potentially useful noninvasive marker of left ventricular dysfunction that is easily obtained from the routine echocardiogram.     

Patient activated asynchronous ventricular pacing at normal rates for termination of ventricular tachycardia

Ventricular pacing has been used to prevent or convert ventricular tachycardia. We report the use of patient-activated asynchronous mode ventricular pacing at normal rates for conversion of ventricular tachycardia by competitive pacing impulses. Following electrophysiologic studies, a specially constructed pacemaker was inserted. Routine function mode resulted in no output but activation of the reed switch resulted in V00 (asynchronous) pacing at 80/min. Patient-initiated conversion of ventricular tachycardia was documented by ambulatory electrocardiographic monitoring. The patient reports an average of two episodes per month converted over a four year period.     

Absence of cardioversion-induced ventricular arrhythmias in patients with therapeutic digoxin levels

To determine the incidence of cardioversion-induced ventricular arrhythmias in patients with therapeutic serum levels of digoxin, 19 patients (average age [+/- standard deviation] 61 +/- 12 years) undergoing elective direct current cardioversion for atrial fibrillation were studied. Only patients with therapeutic serum digoxin levels (range 0.5 to 1.9 ng/ml; mean 1.1 +/- 0.5) at the time of cardioversion were included. Patients with acute myocardial ischemia or unstable angina, serious electrolyte disturbance or those requiring class I antiarrhythmic agents for control of ventricular or supraventricular arrhythmias were excluded. Ambulatory electrocardiograms were recorded for 24 hours before and 6 hours after cardioversion. No patient developed malignant ventricular arrhythmias (ventricular triplets or tachycardia) in the immediate 3 hour period after cardioversion. Furthermore, there were no significant (p less than 0.05) differences in the frequency of ventricular premature beats or couplets before and after cardioversion. To determine whether the level of serum digoxin or the strength of the applied shock had a significant effect on the development of postcardioversion arrhythmias, the change in frequency of single premature ventricular beats after cardioversion was compared with the serum digoxin level (ng/ml) and the applied energy level (joules) by means of linear regression analysis. There was no significant (p less than 0.05) relation between these variables. These findings suggest that patients with therapeutic serum levels of digoxin may safely undergo cardioversion without the concomitant use of class I antiarrhythmic agents.