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.     

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.     

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.     

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.     

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.     

Digital intravenous ventriculography: Analysis and validation of wall thickness changes during ischemia and inotropic stimulation in dogs

To assess regional ventricular wall thickening, we studied 8 open-chest dogs using digital intravenous ventrlculography at a control stage, after subtotal and total coronary occlusion, and then after isoproterenol administration. In 3 dogs, 2 pairs of myocardial thickness crystals were implanted. Correlations of measures of wall thickness and percentage of wall thickening with crystal measures were excellent at the base (r ≥ 0.97) and near the apex (r ≥ 0.97). Four areas of the inferoapical wall muscle were measured: the base, mid-wall, distal wall, and apex. Four chamber dimensions were also examined: the long axis, base, mid-wall, and distal wall. End-diastolic thickness decreased with ischemia. At completion occlusion, it was ? 24.6 ± 6% at the base, ? 27.3 ± 5% at the mid-wall, ? 27.1 ± 5% at the distal wall, and ? 24.7 ± 5% at the apex. Percent thickening decreased with occlusion, although greater at the base and mid-wall than at the distal wall and apex. With Isoproterenol, end-diastolic thickness increased only at the apex, with little change at the base, distal wall, and mid-wall. Percent thickening increased. In general, ischemia produced increases in end-diastolic hemichords with little change in the long axis. Isoproterenol reduced the hemichords, although the long axis did not change.We conclude that digital intravenous ventriculograms can be used to assess changes in wall thickness with high degrees of accuracy. Asymmetric thickening occurred at rest, with ischemia and with inotropic stimulation, being greatest at the apex and least at the base.     

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.     

Cardiomyopathy: How far have we come in 25 years,how far yet to go?

Twenty-five years ago clinical investigators began to appreciate that cardiomyopathy is an important and reasonably common form of heart disease. Since then, several functional classifications have been proposed, the specific myocardial diseases have been classified and chronic ischemic ventricular failure has been described. The boundary separating myocarditis from dilated cardiomyopathy remains hazy and, despite intensive research, the causes of dilated cardiomyopathy remain obscure. In particular, we still do not understand the role that may be played by viral infection and alcohol. Myocardial biopsy has proved useful in patients with specific myocardial disorders, heart transplant recipients and patients receiving Adriamycin, but is disappointing in patients with dilated cardiomyopathy.It has become increasingly evident that exercise capacity does not correlate with ventricular function, being highly dependent on peripheral factors. Measurements of oxygen consumption during exercise promise to be useful in assessing treatment of dilated cardiomyopathy. True restrictive cardiomyopathy is uncommon, and the term should be reserved for cardiomyopathies that meet strict criteria. A restrictive component to filling is common to many cardiac disorders, including some cases of cardiac amyloidosis.The concept of hypertrophic cardiomyopathy has evolved rapidly over the past 25 years, and continues to evolve. The importance of arrhythmia as a cause of sudden death is becoming increasingly clear. The place of calcium channel blocking agents in the treatment of hypertrophic cardiomyopathy will probably emerge soon. Amiodarone is finding an increasing role in the treatment of dilated and hypertrophic cardiomyopathy. Surgical treatment is still required for some patients despite unanswered questions on how it works.     

Tocainide therapy for treatment of ventricular arrhythmias: assessment with ambulatory electrocardiographic monitoring and treadmill exercise

Tocainide has shown promise in the acute suppression of ventricular arrhythmias and in the treatment of such arrhythmias considered refractory to other drugs. However, there is little experience with tocainide therapy using currently acceptable statistical end points in patients not receiving conventional antiarrhythmic drugs concurrently. Accordingly, a double-blind, crossover study design was used to compare the effects of 2 week periods of placebo therapy and small dose (400 mg every 8 hours) tocainide therapy in 10 patients with ventricular arrhythmias who were not receiving quinidlne, procainamide or disopyramide. Ventricular arrhythmias were assessed with 24 hour ambulatory electrocardiographic monitoring and treadmill exercise. Individual patients not responding to small dose tocainide with at least an 80 percent decrease in ventricular premature complexes on ambulatory monitoring were given doses of 600 mg and then 800 mg every 8 hours. Small dose tocainide therapy resulted in a decrease in ventricular premature complexes/hour from 364 ± 98 (standard error) to 127 ± 50 (p < 0.05) and 5 of 10 patients had at least an 80 percent decrease. At higher dose levels, two additional patients had at least an 80 percent decrease. The response of ventricular arrhythmias during treadmill exercise was comparable with that during ambulatory monitoring. Side effects were minor or nonexistent in the seven patients who responded to tocainide, and effective mean serum concentrations were 4.4 ± 1.9 μg/ml, a value significantly lower than that previously reported to suppress refractory ventricular arrhythmias. It is concluded that tocainide is an effective agent in patients not receiving concurrent therapy with conventional agents and that patients selected because of refractory ventricular arrhythmias may require higher serum concentrations of the drug than unselected patients.     

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.     

Peak systolic blood pressure/end-systolic volume ratio: Assessment at rest and during exercise in normal subjects and patients with coronary heart disease

To assess the utility of a recently proposed index of left ventricular performance, the ratio of peak left ventricular systolic pressure to end-systolic volume, equilibrium radionuclide angiography was used to determine end-systolic volume and the systolic blood pressure obtained by cuff sphygmomanometer to determine peak systolic pressure. Data were analyzed at rest and during supine bicycle exercise in 15 normal subjects (Group 1), 50 patients with coronary artery disease (Group II) and 9 patients with obstructive lung disease and no evidence of coronary artery disease on clinical examination including exercise thallium imaging (Group III). In 15 subjects the correlation between the resting angiographic and radionuclide pressure/volume ratio was excellent (r = 0.929, p <0.005).Forty-seven (94 percent) of the 50 patients in Group II had a depressed pressure/volume ratio at rest or an abnormal change in this ratio during exercise, whereas only 43 (86 percent) of this group had an abnormal ejection fraction at rest or during exercise. Additionally, 3 of 15 subjects in Group I had an abnormal ejection fraction response, defined as less than 0.05 ejection fraction unit increase with exercise (specificity 80 percent), whereas all subjects in Group I had a normal increase in pressure/volume ratio (specificity 100 percent). At rest, neither index identified more patients with coronary artery disease than the other. Of the nine patients in Group III, six had an abnormal ejection fraction response to exercise, whereas only one had an abnormal pressure/volume ratio response.It is concluded that the end-systolic pressure/volume ratio is a useful index of left ventricular performance. In some patients during supine exercise stress it may be more sensitive than the ejection fraction response alone in identifying the presence of coronary artery disease.     

Assessment of early ventricular systole by first pass radionuclide angiography: useful method for detection of left ventricular dysfunction at rest in patients with coronary artery disease.

To identify abnormal left ventricular function without exercise stress in patients with coronary artery disease first-pass radionuclide angiograms were analyzed in 32 normal subjects (Group I); 31 patients with coronary disease and normal contrast ventriculograms (Group II); and 17 patients with coronary disease and depressed left ventricular function (Group III). Total ejection fraction (EF) was computed with standard angiographic methods and from each time-activity curve. During the first third of systole, ejection fraction was determined manually by averaging three to five beats and the value compared with that obtained with contrast ventriculography: (Formula: see text). Both total radionuclide ejection fraction (r = 0.95) and first-third ejection fraction (r = 0.91) correlated well with angiography. Intraobserver and interobserver variation was small, averaging 0.02 +/- 0.02 (range 0 to 0.05). The radionuclide first-third ejection fraction was 0.25 or greater in normal subjects and less than 0.25 in 29 of 31 patients (94 percent) in Group II and in all patients in Group III. It is concluded that the first-third ejection fraction obtained with first pass angiography identifies subtle abnormalities of left ventricular function at rest in more than 90 percent of patients with coronary disease that may not be recognized by total ejection fraction alone.     

Sensitivity and specificity of nuclear phase analysis versus ejection fraction in coronary artery disease

Phase standard deviation (SD) and skew characteristics of the first Fourier harmonic of equilibrium radionuclide volume curves were examined and compared during rest and during supine bicycle exercise with ejection fraction (EF) changes and the development of ischemia in 17 control subjects and in 2 groups of patients (n = 57) with coronary artery disease (CAD). Group I comprised 37 patients with CAD; IA was a subgroup of 20 patients with previous myocardial infarction (MI) and IB a subgroup of 17 patients with CAD without MI (all with coronary stenosis greater than 75% diameter narrowing). Group II comprised 20 patients with CAD who had undergone coronary bypass surgery. In the Group I subjects, phase SD was the most sensitive indicator of CAD at rest (Group I, 56%; Group IA, 70%, and Group IB, 29%), and the EF was the most sensitive indicator at submaximal (Group I, 78%; Group IA, 86%, and Group IB, 64%) and maximal exercise (Group I, 70%; Group IA, 93%, and Group IB, 53%). When phase SD and skewness were combined with EF changes, little increase in sensitivity occurred in Group I (rest 61%, submaximal exercise 88% and maximal exercise 76%). The results from Group II subgroups were qualitatively similar to those observed with Group I subgroups. These data reveal a marginally improved sensitivity for detection of CAD during supine bicycle radionuclide ventriculography when phase measurements were added to changes in global EF values.     

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.     

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.     

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.     

Clinical assessment and follow-up of functional capacity in patients with chronic congestive cardiomyopathy

The presumption that the results of left ventricular systolic function tests performed at rest are related to the symptoms of chronic congestive heart failure or to exercise capacity is unproved. Thirty-three patients with chronic congestive Cardiomyopathy underwent serial exercise tests, determinations of ejection fraction and systolic time intervals, echocardiograms, assessment of symptom score, chest roentgenogram, and physical examination over a mean (± standard deviation) of 24.8 ± 14.1 months. Maximal exercise performance achieved correlation with symptoms (r = −0.66) but not with indexes of left ventricular function. Edema, elevated jugular venous pressure, rales and radiologic evidence of pulmonary venous hypertension were more common in patients with severe limitation of exercise capacity. In 17 patients whose functional capacity changed during the follow-up period, congruent changes in left ventricular function measured at rest were not consistently observed.

Thus the findings on history, physical examination and radiologic examination correlate with exercise capacity, but indexes of left ventricular performance at rest do not and therefore are of limited use in assessing treatment. The clinical course of patients with chronic congestive cardiomyopathy can be followed up safely, effectively and economically by simple clinical observations. Serial laboratory testing of left ventricular function can be reserved for specific indications, research and patients with valvular heart disease.