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Practical Significance of Systolic Time Intervals in Coronary Artery Disease
Practical Significance of Systolic Time Intervals in Coronary Artery Disease* David Rater, M.D.,0° David Pugh, M.D.,t and Wayne Gray, M.D.t
Systolic time interval meMurements were compared to the left ventricular ejection fractions (LVEF) calculated from angiograms in 44 patients with chest pain to determine if left ventricular dysfunction could be predicted using this noninvasive method. Correlation of the pre-ejection phase index (PEPI) and L VEF was significant, in that a longer PEPI was associated with a low LVEF (r= -0.65). Determination of the ratio of pre-ejection period/left ventricular ejection time offered no advantage over the PEPI in determination of the L VEF (r= -0.67). Although a PEPI of 150 or greater was always associated with a low L VEF, estimation of the L VEF in any given patient could not be made with precision, using this phonocardiographic measurement; however, the use of the PEPI may have limited value in screening patients with severe ischemic heart disease.
Jt has been suggested that systolic time intervals
provide a simple, accurate, noninvasive method of evaluating cardiac function. Significant correlation has been shown between systolic time intervals and direct measurements of left ventricular function in heterogeneous groups of patients. 1•3 Whether measurement of systolic time intervals will provide an accurate estimate of left ventricular function in patients with coronary artery disease to allow practical application is yet to be established. 4 Since the myocardial component of ischemic heart disease is extremely important, determination of left ventricular function by a noninvasive technique has obvious advantage. The purpose of this study was to determine the practical significance of systolic time intervals in predicting abnormal left ventricular function in patients with coronary artery disease. SUBJECTS AND METHODS
Studies were made of 44 patients undergoing selective coronary angiography for the evaluation of chest pain. Pa0From the Cardiovascular Laboratory, University of Kansas Medical Center, Kansas City. 0 °Fellow in Cardiology. t Associate Professor of Medicine. !Assistant Professor of Medicine. Supported in part by a grant from the Kaw Valley Heart Association. Manuscript received October 13, 1972; revision accepted March 5, 1973. Reprint requests: Dr. Gray, University of Kansas Medical Center, 39th and Rainbow, J.<:ansos. City, Kansas 66103
186
tients with valvular heart disease, hypertension, overt congestive heart failure, arrhythmias, incomplete or complete left bundle branch block, left anterior or posterior hemiblock, or receiving negative inotropic drugs were excluded. Three patients had received digitalis. All patients had an electrocardiogram and vectorcardiogram immediately prior to the phonocardiogram. Systolic time interval measurements were made from a simultaneous recording of the heart sounds, right external carotid pulse, and an ECG lead at a paper speed of 100 mm/sec with 0.01 sec time lines taking an average of five consecutive beats. Measurements were made to the nearest 5 sec. An Elema-Schonander Mingograf 81 recording system was used. Heart sounds were recorded with Elema-Schonander EMT 25 B piezoelectric accelerometer microphones strapped firmly over both the third and fifth left interspaces along the left sternal border, with an EMT 28 filter set to record maximum amplitude at a frequency at 200/Hz. The carotid pulse was recorded using an Elema-Schonander EMT510C crystal transducer held manually. Recordings were made with the patients in the supine position, usually the morning before catheterization. The pre-ejection phase ( PEP) was defined as that period from the onset of electrical depolarization ( Q wave) to the onset of left ventricular ejection, and was obtained by subtracting the left ventricular ejection time ( LVET) from the Q-A2 interval to correct for the delay in transmission from the proximal aorta to the carotid. The L VET was that period from the onset of the rapid upstroke of the carotid pulse to the trough of its incisura. The Q-A~ interval was that period from the onset of electrical depolarization to the end of left ventricular ejection, as measured by the aortic closure sound. The pre-ejection phase index ( PEPI ) was determined by correcting for heart rate, using the formula heart rate X 0.4 PEP as established by Weissler. A normal PEPI was 133±
+
CHEST, VOL. 64, NO. 2, AUGUST, 1973
187
SYSTOLIC TIME INTERVALS IN CORONARY ARTERY DISEASE 11 for men and 131± 13 for women.2 Selective coronary and left ventricular angiography was done using the Judkins' technique.5 Cine films were recorded in several planes on 35 mm film. The coronary arteriograms were graded as 0 for normal, 1 + for less than 50 percent narrowing of a major coronary artery, 2+ for lesions equal to 50 percent obstruction of a major coronary artery, 3+ for proximal lesions producing greater than 50 percent narrowing of a major coronary artery but normal or nearly normal distal vessel, and 4+ for diffuse disease with both proximal and distal obstruction greater than 50 percent in a major vessel or total proximal occlusion of a single major vessel with no filling of the distal portion of that vessel either primarily or by collateral circulation. Right heart catheterization was performed using a percutaneous technique from the right femoral vein with wedge pressure determinations using a no. 6 French Lehman catheter. Premedication was not given prior to either the cardiac catheteri~tion or the recording of systolic time intervals. The cardiac index and stroke index were obtained on 36 patients, using the Fick method. Pressures were recorded through fluid-filled catheters using Statham P23DB strain gauges and an Electronics for Medicine Model DR-8 recorder. Left ventricular end diastolic pressure was recorded in all patients. Left ventricular cineangiograms were recorded in a 30-degree right anterior oblique position following injection of a 50 ml bolus of meglumine diatrizoate and sodium diatrizoate through a no. 8 French pigtail catheter situated in the left ventricle at 400 pounds per square inch (psi). Left ventricular chamber volume was calculated according to a modification of the method of Dodge.6 Ejection fractions were calculated in all EDV-ESV /EDV. An ejection patients as follows: EF fraction of less than 0.55 was considered indicative of abnormal left ventricular function. 7
=
REsULTS
Correlation Between the Systolic Time Intervals and Extent of Coronary Artery Disease There were 35 men and nine women studied, ranging from 32-66 years of age. Significant coronary disease, either 3 + or 4 +, was found in 30 of the 44 patients. There were nine patients with normal coronary arteries or minimal ( 1 + ) coronary disease and five patients with 2 + coronary disease. Figure 1 shows the distribution of patients with respect to the severity of the coronary artery disease and the cor-
.
180 170 160 PRE- EJECTION 150 PHASE 140 INDEX 130
120 110 100
.•
•
. . . l
. .• • •• •
2+ 3+ 0-1• CORONARY ARTERY DISEASE
•
... .•••••. • .. r
EJECTION .a FRACTION .6
. . ---:-.....:
-----·
n• 44
2
r
•·0.65
EF•1.76-0.0085(PEPII
000~--~--~QO~--~---=.~~--~--~.~~--~--~~ PEP!
FIGURE 2. Correlation of pre-ejection phase index and ejection fraction.
responding PEP!. In general, the patients with the most prolonged PEPI were those with 4 + coronary disease. However, many patients with 4 + disease had normal PEPI values.
Correlations Between the Systolic Time Intervals and Hemodynamics Correlation of the ejection fraction with the PEPI is shown in Figure 2. A statistically significant correlation of -0.65 is demonstrated. Figure 3 is a correlation of the PEP I LVET and ejection fraction which shows a similar correlation of - 0.67, which is not significantly different from the correlation of the ejection fraction with the PEP!. All ten patients with a PEPI of 150 or greater had abnormal left ventricular function, with ejection fractions of less than 0.55 ( P less than 0.005). An ejection fraction of less than 0.55 was found in 19 of the 44 patients studied. A normal PEPI was present in nine of those 19 patients with a low ejection fraction. All 19 patients had significant coronary artery disease. Figure 4 is an example of a patient with a markedly prolonged PEPI and abnormal left ventricular ejection fraction. The correlation of the stroke index with both the PEPI and the PEP I LVET in 36 patients in whom cardiac output was determined was not statistically significant ( r= -0.4). Neither the PEPI nor the PEPI LVET showed a consistent relationship to the left ventricular end diastolic pressure. An elevated left ventricular end diastolic pressure was seen
.. ... . .'.' . . ..
1.0
.a EJECTION FRACTION
.6 J4
n • 44 r •-0.67
..
.2 EF•1.23·1.6(PEP/LVET)
4+
FIGURE 1. Severity of coronary artery disease compared to pre-ejection phase index.
CHEST, VOL. 64, NO. 2, AUGUST, 1973
1.0
.0 .0
2
.3
5
.6
.7
PEP/LVET
FIGURE 3. Correlation of pre-ejection pha~e index/left ventricular ejection time and ejection fraction.
188
RATER, PUGH, GRAY
f,,.M~....,.--,..,,_.,,,~.,
" ~·'
•
PEPI 1e2
The use of the PEPI does have some qualitative value with respect to left ventricular function. Although the presence of a normal PEPI clearly does not exclude significant coronary disease or abnormal left ventricular function, a markedly prolonged PEPI of 150 or greater was always associated with significant coronary artery disease and abnormal left ventricular function. All ten of the 44 patients studied with a markedly prolonged PEPI of 150 or greater had ischemic cardiomyopathy with severe diffuse coronary disease. All of these patients had electrocardiographic and vectorcardiographic evidence of old myocardial infarctions. It is concluded that the PEPI measurements have limited practical application in patients with coronary artery disease. Abnormal PEPI values in patients suspected of having coronary artery disease usually mean severe diffuse end stage ischemic cardiomyopathy. ACKNOWLEDGMENT: We would like to thank Mrs. Betty Smith and Mrs. Lou Kelly for their assistance in the preparation of this manuscript. REFERENCES
FIGURE 4. Example of patient with severe ( 4+) coronary artery disease and abnormal left ventricular ejection fraction with prolonged pre-ejection phase index.
in patients with both normal and abnormal systolic time intervals. DISCUSSION
Although the correlation of the PEPI and PEP/LVET with ejection fractions was statistically significant, it is obvious that precise determination of an ejection fraction from any given value of either of these two systolic time intervals is limited. This limitation significantly reduces the value of this noninvasive method in quantitatively estimating left ventricular function in patients with coronary disease. These data are in agreement with a previous study in patients with chronic coronary artery disease. 8 Since there are many variables influencing systolic time intervals, this practical limitation is not altogether unexpected. 9
1 Garrad CL, Weissler AM, Dodge HT: The relationship of alterations in systolic time intervals to ejection fraction in patients with cardiac disease. Circulation 42:455-462, 1970 2 Weissler AM, Harris WS, Schoenfeld CD: Systolic time intervals in heart failure in man. Circulation 37:149-159, 1968 3 Martin EC, Shaver JA, Thompson ME, et a!: Direct correlation of external systolic time intervals with internal indices of left ventricular function in man. Circulation 44:419-431, 1971 4 Perloff JK, Reichek N: Value and limitations of systolic time intervals (pre-ejection period and ejection time) in patients with acute myocardial infarction (editorial ) . Circulation 45:929-932, 1972 5 Judkins M: Selective coronary arteriography: 1. A percutaneous transfemoral technique. Radiology 89:815-824, 1967 6 Dodge HT, Sandler H, Baxley WA, et al: Usefulness and limitation of radiographic methods for determining left ventricular volume. Am J Cardiol18:10-24, 1966 7 Kennedy JW, Baxley WA, Figley MM, et al: Quantitative angiography; 1. The normal left ventricle in man. Circulation 34:272-278, 1966 8 McConahay DR, Martin CM, Cheitlin MD: Resting and exercise systolic time intervals: Correlation with ventricular performance in patients with coronary artery disease. Circulation 45:592-601, 1972 9 Weissler AM, Garrard CL: Systolic time intervals in cardiac disease. Mod Concepts Cardiovasc Dis 15:1-8, 1971
CHEST, VOL. 64, NO. 2, AUGUST, 1973
Systolic time interval meMurements were compared to the left ventricular ejection fractions (LVEF) calculated from angiograms in 44 patients with chest pain to determine if left ventricular dysfunction could be predicted using this noninvasive method. Correlation of the pre-ejection phase index (PEPI) and L VEF was significant, in that a longer PEPI was associated with a low LVEF (r= -0.65). Determination of the ratio of pre-ejection period/left ventricular ejection time offered no advantage over the PEPI in determination of the L VEF (r= -0.67). Although a PEPI of 150 or greater was always associated with a low L VEF, estimation of the L VEF in any given patient could not be made with precision, using this phonocardiographic measurement; however, the use of the PEPI may have limited value in screening patients with severe ischemic heart disease.
Jt has been suggested that systolic time intervals
provide a simple, accurate, noninvasive method of evaluating cardiac function. Significant correlation has been shown between systolic time intervals and direct measurements of left ventricular function in heterogeneous groups of patients. 1•3 Whether measurement of systolic time intervals will provide an accurate estimate of left ventricular function in patients with coronary artery disease to allow practical application is yet to be established. 4 Since the myocardial component of ischemic heart disease is extremely important, determination of left ventricular function by a noninvasive technique has obvious advantage. The purpose of this study was to determine the practical significance of systolic time intervals in predicting abnormal left ventricular function in patients with coronary artery disease. SUBJECTS AND METHODS
Studies were made of 44 patients undergoing selective coronary angiography for the evaluation of chest pain. Pa0From the Cardiovascular Laboratory, University of Kansas Medical Center, Kansas City. 0 °Fellow in Cardiology. t Associate Professor of Medicine. !Assistant Professor of Medicine. Supported in part by a grant from the Kaw Valley Heart Association. Manuscript received October 13, 1972; revision accepted March 5, 1973. Reprint requests: Dr. Gray, University of Kansas Medical Center, 39th and Rainbow, J.<:ansos. City, Kansas 66103
186
tients with valvular heart disease, hypertension, overt congestive heart failure, arrhythmias, incomplete or complete left bundle branch block, left anterior or posterior hemiblock, or receiving negative inotropic drugs were excluded. Three patients had received digitalis. All patients had an electrocardiogram and vectorcardiogram immediately prior to the phonocardiogram. Systolic time interval measurements were made from a simultaneous recording of the heart sounds, right external carotid pulse, and an ECG lead at a paper speed of 100 mm/sec with 0.01 sec time lines taking an average of five consecutive beats. Measurements were made to the nearest 5 sec. An Elema-Schonander Mingograf 81 recording system was used. Heart sounds were recorded with Elema-Schonander EMT 25 B piezoelectric accelerometer microphones strapped firmly over both the third and fifth left interspaces along the left sternal border, with an EMT 28 filter set to record maximum amplitude at a frequency at 200/Hz. The carotid pulse was recorded using an Elema-Schonander EMT510C crystal transducer held manually. Recordings were made with the patients in the supine position, usually the morning before catheterization. The pre-ejection phase ( PEP) was defined as that period from the onset of electrical depolarization ( Q wave) to the onset of left ventricular ejection, and was obtained by subtracting the left ventricular ejection time ( LVET) from the Q-A2 interval to correct for the delay in transmission from the proximal aorta to the carotid. The L VET was that period from the onset of the rapid upstroke of the carotid pulse to the trough of its incisura. The Q-A~ interval was that period from the onset of electrical depolarization to the end of left ventricular ejection, as measured by the aortic closure sound. The pre-ejection phase index ( PEPI ) was determined by correcting for heart rate, using the formula heart rate X 0.4 PEP as established by Weissler. A normal PEPI was 133±
+
CHEST, VOL. 64, NO. 2, AUGUST, 1973
187
SYSTOLIC TIME INTERVALS IN CORONARY ARTERY DISEASE 11 for men and 131± 13 for women.2 Selective coronary and left ventricular angiography was done using the Judkins' technique.5 Cine films were recorded in several planes on 35 mm film. The coronary arteriograms were graded as 0 for normal, 1 + for less than 50 percent narrowing of a major coronary artery, 2+ for lesions equal to 50 percent obstruction of a major coronary artery, 3+ for proximal lesions producing greater than 50 percent narrowing of a major coronary artery but normal or nearly normal distal vessel, and 4+ for diffuse disease with both proximal and distal obstruction greater than 50 percent in a major vessel or total proximal occlusion of a single major vessel with no filling of the distal portion of that vessel either primarily or by collateral circulation. Right heart catheterization was performed using a percutaneous technique from the right femoral vein with wedge pressure determinations using a no. 6 French Lehman catheter. Premedication was not given prior to either the cardiac catheteri~tion or the recording of systolic time intervals. The cardiac index and stroke index were obtained on 36 patients, using the Fick method. Pressures were recorded through fluid-filled catheters using Statham P23DB strain gauges and an Electronics for Medicine Model DR-8 recorder. Left ventricular end diastolic pressure was recorded in all patients. Left ventricular cineangiograms were recorded in a 30-degree right anterior oblique position following injection of a 50 ml bolus of meglumine diatrizoate and sodium diatrizoate through a no. 8 French pigtail catheter situated in the left ventricle at 400 pounds per square inch (psi). Left ventricular chamber volume was calculated according to a modification of the method of Dodge.6 Ejection fractions were calculated in all EDV-ESV /EDV. An ejection patients as follows: EF fraction of less than 0.55 was considered indicative of abnormal left ventricular function. 7
=
REsULTS
Correlation Between the Systolic Time Intervals and Extent of Coronary Artery Disease There were 35 men and nine women studied, ranging from 32-66 years of age. Significant coronary disease, either 3 + or 4 +, was found in 30 of the 44 patients. There were nine patients with normal coronary arteries or minimal ( 1 + ) coronary disease and five patients with 2 + coronary disease. Figure 1 shows the distribution of patients with respect to the severity of the coronary artery disease and the cor-
.
180 170 160 PRE- EJECTION 150 PHASE 140 INDEX 130
120 110 100
.•
•
. . . l
. .• • •• •
2+ 3+ 0-1• CORONARY ARTERY DISEASE
•
... .•••••. • .. r
EJECTION .a FRACTION .6
. . ---:-.....:
-----·
n• 44
2
r
•·0.65
EF•1.76-0.0085(PEPII
000~--~--~QO~--~---=.~~--~--~.~~--~--~~ PEP!
FIGURE 2. Correlation of pre-ejection phase index and ejection fraction.
responding PEP!. In general, the patients with the most prolonged PEPI were those with 4 + coronary disease. However, many patients with 4 + disease had normal PEPI values.
Correlations Between the Systolic Time Intervals and Hemodynamics Correlation of the ejection fraction with the PEPI is shown in Figure 2. A statistically significant correlation of -0.65 is demonstrated. Figure 3 is a correlation of the PEP I LVET and ejection fraction which shows a similar correlation of - 0.67, which is not significantly different from the correlation of the ejection fraction with the PEP!. All ten patients with a PEPI of 150 or greater had abnormal left ventricular function, with ejection fractions of less than 0.55 ( P less than 0.005). An ejection fraction of less than 0.55 was found in 19 of the 44 patients studied. A normal PEPI was present in nine of those 19 patients with a low ejection fraction. All 19 patients had significant coronary artery disease. Figure 4 is an example of a patient with a markedly prolonged PEPI and abnormal left ventricular ejection fraction. The correlation of the stroke index with both the PEPI and the PEP I LVET in 36 patients in whom cardiac output was determined was not statistically significant ( r= -0.4). Neither the PEPI nor the PEPI LVET showed a consistent relationship to the left ventricular end diastolic pressure. An elevated left ventricular end diastolic pressure was seen
.. ... . .'.' . . ..
1.0
.a EJECTION FRACTION
.6 J4
n • 44 r •-0.67
..
.2 EF•1.23·1.6(PEP/LVET)
4+
FIGURE 1. Severity of coronary artery disease compared to pre-ejection phase index.
CHEST, VOL. 64, NO. 2, AUGUST, 1973
1.0
.0 .0
2
.3
5
.6
.7
PEP/LVET
FIGURE 3. Correlation of pre-ejection pha~e index/left ventricular ejection time and ejection fraction.
188
RATER, PUGH, GRAY
f,,.M~....,.--,..,,_.,,,~.,
" ~·'
•
PEPI 1e2
The use of the PEPI does have some qualitative value with respect to left ventricular function. Although the presence of a normal PEPI clearly does not exclude significant coronary disease or abnormal left ventricular function, a markedly prolonged PEPI of 150 or greater was always associated with significant coronary artery disease and abnormal left ventricular function. All ten of the 44 patients studied with a markedly prolonged PEPI of 150 or greater had ischemic cardiomyopathy with severe diffuse coronary disease. All of these patients had electrocardiographic and vectorcardiographic evidence of old myocardial infarctions. It is concluded that the PEPI measurements have limited practical application in patients with coronary artery disease. Abnormal PEPI values in patients suspected of having coronary artery disease usually mean severe diffuse end stage ischemic cardiomyopathy. ACKNOWLEDGMENT: We would like to thank Mrs. Betty Smith and Mrs. Lou Kelly for their assistance in the preparation of this manuscript. REFERENCES
FIGURE 4. Example of patient with severe ( 4+) coronary artery disease and abnormal left ventricular ejection fraction with prolonged pre-ejection phase index.
in patients with both normal and abnormal systolic time intervals. DISCUSSION
Although the correlation of the PEPI and PEP/LVET with ejection fractions was statistically significant, it is obvious that precise determination of an ejection fraction from any given value of either of these two systolic time intervals is limited. This limitation significantly reduces the value of this noninvasive method in quantitatively estimating left ventricular function in patients with coronary disease. These data are in agreement with a previous study in patients with chronic coronary artery disease. 8 Since there are many variables influencing systolic time intervals, this practical limitation is not altogether unexpected. 9
1 Garrad CL, Weissler AM, Dodge HT: The relationship of alterations in systolic time intervals to ejection fraction in patients with cardiac disease. Circulation 42:455-462, 1970 2 Weissler AM, Harris WS, Schoenfeld CD: Systolic time intervals in heart failure in man. Circulation 37:149-159, 1968 3 Martin EC, Shaver JA, Thompson ME, et a!: Direct correlation of external systolic time intervals with internal indices of left ventricular function in man. Circulation 44:419-431, 1971 4 Perloff JK, Reichek N: Value and limitations of systolic time intervals (pre-ejection period and ejection time) in patients with acute myocardial infarction (editorial ) . Circulation 45:929-932, 1972 5 Judkins M: Selective coronary arteriography: 1. A percutaneous transfemoral technique. Radiology 89:815-824, 1967 6 Dodge HT, Sandler H, Baxley WA, et al: Usefulness and limitation of radiographic methods for determining left ventricular volume. Am J Cardiol18:10-24, 1966 7 Kennedy JW, Baxley WA, Figley MM, et al: Quantitative angiography; 1. The normal left ventricle in man. Circulation 34:272-278, 1966 8 McConahay DR, Martin CM, Cheitlin MD: Resting and exercise systolic time intervals: Correlation with ventricular performance in patients with coronary artery disease. Circulation 45:592-601, 1972 9 Weissler AM, Garrard CL: Systolic time intervals in cardiac disease. Mod Concepts Cardiovasc Dis 15:1-8, 1971
CHEST, VOL. 64, NO. 2, AUGUST, 1973