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Computerized system for noninvasive techniques
METHODS
Computerized System for Noninvasive Techniques I. Its
Value for Systolic Time Intervals
SAMUEL ZONERAICH, MD, FACC OLGA ZONERAICH, MD JOHN RODENRYS, MS Jamaica, Queens, and Stony Brook,
New York
From the Department of Medicine, Division of Cardiology, Queens Hospital Center, Long Island Jewish-Hillside Medical Center, Clinical Campus of the School of Medicine, State University of New York at Stony Brook, Stony Brook, N. Y. Manuscript accepted August 9. 1973. Address for reprints: Samuel Zoneraich. MD, Division of Cardiology, Queens Hospital Center, 82-88 164 St., Jamaica, Queens. N. Y. 11432.
A total computerized system for the study of the noninvasive techniques and especially for external systolic time intervals is presented. Heart rate, left ventricular ejection time index (LVETI), Q-S2 I (electromechanical index), preejection period (PEP), PEP/LVET ratio, isovolumic contraction time corrected for pulse transmission (ICTc), electromechanical interval (EMI), mechanical systole (St-Sp), DA/D1 (quantitative apex cardiogram) and heart sounds were calculated from simultaneous recordings of electrocardiogram, carotid pulse and apex cardiogram by a multichannel, multifilter Cambridge MCIV phonocardiograph and by a CVAI94 unit MDS computer program. A parallel study of these variables in 100 healthy persons by conventionat manual calculations made from the Cambridge recordings and by the CVA/94 MDS computer system revealed identical results. The computerized system could more rapidly and accurately calculate many variables for systolic time intervals, thus offering the possibility for better evaluation of left ventricular function. Regression equations in relation to heart rate were found only for O-Sn = 520.4 - 1.79 heart rate; LVET = 417.5 - 1.59 heart rate; and S1-S1 = 435.7 - 1.58 heart rate. IClc and EMI differences were negatively correlated at the P = 0.001 level. LVETI and D-Si correlated positively at the P = 0.01 level. DA/D1 reflecting quantitative apex cardiography could be calculated only by computer.
An extensive search for the potential usefulness of noninvasive methods in cardiology has been made in this laboratory’-5 and others during the last few years. Data have been accumulated on the duration of various phases of cardiac systole by using simultaneous external polycardiographic techniques. The durations of these phases, when studied by noninvasive methods, were found to be altered in many abnormal cardiac states. The use of systolic time intervals has been criticized because the regression equation in relation to heart rate varies widely in normal control subjects as studied by various groups and because there are problems of methodology and experimental design.6 A review of normal values for systolic time intervals compiled from 14 original papers7-20 indicates the wide range of these variables in normal subjects (Table I). The purpose of this study was (1) to determine the usefulness of a rapid computer analysis for the measurement of systolic time intervals; (2) to eliminate human error in a parallel study by comparing the data obtained from conventional high fidelity equipment and manual measurements, with those obtained by a computerized system; (3) to calculate, through a computerized system, a large number of known variables, for a better and broader evaluation of left ventricular function; and (4) to compute new variables, not obtainable by conventional means.
May 1974
The American Journal of CARDIOLOGY
Volume 33
643
COMPUTERKED
SYSTEM
FOR
NDNINVASIVB
TBCflNtQUES-ZONERACH
ET AL.
TABLE I Normal
Values
for Systolic
Time
Intervals
in 14 Studies*
Subjects Authors
(no.)
Q-S,
et al.’
211
(M) QS, = 2.1 HR + 546 rt 14 (F) QS,= 2.0 H R + 549 It 14
Weissler
Kumar
& Spodick8
50
Fabian
et al.9
50
Diamant Jain
& Killiplo
& LindahI”
Hamosh
et al.l2
McConahay
et al.13
Chaitiraphan Goldberg” Tavel
81
et al.16
0.49 set - 0.0017 X HR + 0.017
0.11 set x HRI
0.38 set - 0.0013 x HR rt 0.019
12
539 - 2.00 HR f. 15.9
42
-0.020 x HR + 0.522
-0.0004 x HR + 0.0126
-0.0016 0.394
33
Weissler
Weissler
. .
et al.
0.0003 0.015
et al.
ICT
EMI
PTT (msec)
...
...
...
...
22 + 9.8
...
(F) 1.6 H R + 418 ZE 10
35
1.41 HR zt
x HR +
... 464 - 1.49 HRfl6 ...
NC 70.9 f. 15.8 70 It 9.5
...
23
0.052 set - 0.0002 X HR +z 0.015
...
...
. .
...
...
...
...
. 9.
...
...
...
...
Weissler
et al.
...
...
...
Weissler
et al.
...
...
...
...
27
...
Identical to Weissler et al.
...
...
...
...
65-0.17HRf12
...
...
. 9.
...
...
40
et aLM
1.7 HR + 413
S,-8)
f 10
389 13
et aLI7
Lindquist
+ 11
(M)
126 - 0.34 H R f 12
Hodges
& Goldberg18
+ 13 0.4 HR + 133
-159 + 503 HR ZIz 14
139
et al.‘9
0.4 HR + 131
376 - 1.2 HR f 12
et aLI
Austin
LVET
NC
Heikkila
Whitsett
PEP
Weissler
et al.
2.33 HR + Q-S,
...
...
10
...
21
Weissler
et al.
Weissler
NC HR 90 f
-2.22 HR + -443.7
. .
2.3
Weissler
...
et al.
et al.
..
-1.85 HR + 502 f 16
-0.44 rt9
HR + 117
-1.42 HR + 385 =!z 12
456 - 1.8 HRf 15
Diamant
& Killip
...
...
...
..a
52.4 f
14.9
24.7 z+z 10.2
...
..
-0.07
HR + 32
..
. ..
f 10
Because of different characteristics of phonocardiographic machines, several groups established their own normal values. Other groups used formulas established by one or two investigators. EMI = electromechanical interval: HR = heart rate; ICT = isovolumic contraction time; LVET = left ventricular ejection time; NC = no correlation with heart rate; PEP = preejection period; PTT = pulse transmission time; Q-S, = electromechanical systole; S1-S2 = mechanical systole.
seconds were used to record the apex cardiogram and carotid pulse (funnel shape pick-up). A Cambridge 2100-4 microphone was used to record the phonocardiogram. The paper speed was 100 mm/set. A Cambridge l-206, five lead cable was used to record lead II of the electrocardiogram. The MDS system utilized a Hewlett-Packard 21050 to record the carotid pulse and a single direct contact microphone 21050 A to record the apex cardiogram and phonocardiogram. A Hewlett-Packard 14056-B, three lead electrocardiographic cable was used to record lead II. After verification of proper signal placement, using the oscilloscope monitor on the CVAl94 cart, a simultaneous 10 second recording was made on the CVAl94 strip chart and on the magnetic tape using a frequency modulation (FM) recording technique.
Material and Methods One hundred ambulatory, nonhospitalized persons, ranging in age from 17 to 62 years (mean 36.6), with no history of heart disease were included in this study. The number of men and women was almost equal. All subjects had a normal history, normal cardiovascular system on clinical examination, normal electrocardiogram, a systolic pressure of 140 mm Hg or less and a diastolic pressure of 90 or less. They were receiving no medication, The studies were performed at approximately the same time (early in the morning). The subjects were placed in the left lateral decubitus. During held expiration a 10 second recording was made of simultaneous apex cardiogram, carotid pulse tracing, phonocardiogram and lead II electrocardiogram with a Cambridge multichannel MCIV recorder and immediately after with the Medical Data Systems (MDS) CVA/94 unit (Medical Data Systems, Inc., San Diego, Calif.) (Fig. 1). l-665 Cambridge pulse transducers with a time constant of 3.5
644
May 1974
The American
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of CARDIOLOGY
Volume
Intervals The following variables were computed with the CVAl94 computer program and, conventionally, by MCIV Cambridge recording:
33
CDh&WERlZED
FIGURE 1. Schematic drawing of flow of patient signals during study using recordings and data processing performed by the Cambridge recorder and conventional calculation and by the CVA/94 unit MDS computer system. ACG = apex cardiogram, CPP = carotid pulse; ECG = electrocardiogram; PCG = phonocardiogram.
SYSTEM FDR NDNWWASIVE
TECHNlQlJES-ZDNERACH
computer
a”alySlS
STI comp”tat,ms
cornpu,er O”tputrwxOfllnlplotS
\
ET AL.
heart sound
~~mp”,at,~n
V
Heart rate: R-R interval (beats/min). Left ventricular ejection time index (LVETZ): carotid upstroke to trough of carotid incisura, corrected for heart rate. Electromechanical systole index (Q-S, I): Q wave of the electrocardiogram to the aortic component of the second heart sound, corrected for heart rate. Preejection period (PEP): Q wave to leg of upstroke of the carotid pulse, corrected for pulse transmission time. Electromechanical interval (EMZ): Q wave to upstroke of apex cardiogram. Zsovolumic contraction time, corrected for pulse transmission time (ICTc): (a) leg of upstroke of apex cardiogram to leg of upstroke of carotid pulse, corrected for pulse transmission time; (b) (leg of apex cardiogram to second heart sound) minus left ventricular ejection time. PEP/LVET: ratio of preejection period to left ventricular ejection time. Quantitative apex cardiogram (DAIDT) (calculated only by computer): ratio of the relative excursion of the apex cardiogram from leg of upstroke to the point of maximal slope (rate of change of apex cardiogram) divided by the interval between the Q wave of the electrocardiogram and the time of maximal slope.
Manual Analysis Manual calculations of the systolic time intervals obtained with the Cambridge MCIV recording were read to the nearest 5 msec for 10 consecutive cycles. The rate-dependent raw values were corrected for heart rate and then averaged to obtain a representative value. Raw values that were not rate-dependent were directly averaged to obtain a representative value.
back into the CDC 1700 computer through an analog tape recorder and the signals digitized at the rate of 1,000 times/ set for 10 seconds. After analog to digital conversion, an interactive graphics monitor was used to display the digital signals. A check was made at this time for artifactual or missing signals. After verification of satisfactory signals, the patient’s signals were written on digital magnetic tape. The CVA/94 computer program analysis was performed on a CDC 1700 computer using the digital magnetic tape that was previously written. During the processing, 10 consecutive cardiac cycles were analyzed. The computer performed two basic functions; detection of heart sounds and computation of systolic time intervals. During the computer analysis, all rate-dependent intervals were converted into their respective indexes. At the completion of processing, a 45 line printer and a computer output microfilm (C.O.M.) tape were generated. In addition, 700 items of information on each patient were printed on the line printer for the basic reference file. The C.O.M. tape was taken to a Datagraphic X4020 C.O.M. computer which produced graphs of the original signals of the patients (Fig. 2 and 3) with computer-generated annotations. These plots are for physician review of configuration and computer accuracy. The graphs are stored on microfilm and 11 by 11 bond paper. Normal values for the interval are printed by the computer for comparison. The computer program also provides data on the time of occurrence of the following heart sounds: systolic clicks, aortic component of the second heart sound (As), opening snap, third (Ss) and fourth (Sd) heart sounds and the mitral component of the first heart sound @I).
Computer Processing
Comparison and Statistical Analysis
The recordings made on the magnetic tape were processed by computer in two stages: (1) analog to digital conversion, and (2) CVA/94 computer program analysis. The analog to digital conversion was performed on a CDC 1700 computer. The analog tape cassettes were played
During the statistical comparison, the data from the Cambridge tracings and the Medical Data Systems computer program were assumed to be from two different populations. A Student t test for the differences between the means of two variables was performed. A correlation study,
May 1974
The Amerkan
Journal of CARDIOLOGY
Volume 33
645
coMpuTERuzD
SYSTEM FOR NQNINVASIVE
lW%WQUES--2ONEFtAtCl.l
El
AL.
FIGURE 2. Computer graphs of the original patient signals. From top to bottom: electrocardiogram. carotid pulse tracing, apex cardiogram and phonocardiiram. Numbers at top identify patients code number, hospital code number and tape file Index.
;
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cardiac cycle. The figures are registered on the chart. From top to bottom: electrocardiogram, carotid pulse tracing, apex cardiogram and phonocardiogram. The pattent’s code nufffber, hospital code number, taupe file index and both the first and second heart sounds are indicated. Values are shown for cycle number, heart fate, pfeejection period, true isovolumic contraction time, isovolumic contractlon time and left ventricular ejection time (LVET).
CmZED
SYSTEM FOR NDNINVASIVE
ET AL.
Discussion Our study clearly demonstrates that many of the disadvan~ges of using systolic time intervals could be avoided by using better techniques of recording and calculating these intervals. Our approach for recording multiple variables is based on theoretical and practical considerations indicating that no single measure has proved to be of unchallenged superiority in evaluating left ventricular function and that the interpretation of results obtained by any method must be qualified by recognition of the limitations of the technique. It is important to realize that the early vibrations of the first heart sound21,22 are occasionally difficult to identify for calculation of isovolumic contraction time, that the latter may increase the value of preejection period as a measure of left ventricular performance and, finally, that newer variables such as electromechanical interval and DA/DT may reflect significant events in the cardiac cycle. Use of the apex cardiogram for the calculation of isovolumic contraction time diminishes the wide variability encountered in the normal population when measurements for this variable are based on the identification of a high vibration in the first heart sound. Recording of the apex cardiogram requires minimal experience. Poor or unobtainable tracings due to obesity, chronic lung disease or other causes occur in less than 10 percent of recordings in our experience. Minimal arterial distortion resulting from filtering and information gain are occasionally encountered in obese subjects when the arterial pulse is recorded.23 Our data indicate that the preejection period could not be corrected for heart rate, since heart rate has a
using the null hypothesis, was also performed to determine the relation between the differences of the variables.
ResuRs As shown in Table II, none of the differences between the manual and the computer results were significant (6 values were at the P = 0.50 level and 1 was at the P = 0.30 level), indicating that the computer system was almost duplicating the results obtained by manual, conventional calculation of the Cambridge recorded signals. The results indicate only two significant relations among the differences. Differences for isovolumic contraction time, corrected for pulse transmission time (ICTc), correlated negatively with each other at the P = 0.001 level. This is an expected finding, since a prolonged ICTc interval will shorten the electromechanical interval and vice versa. Left ventricular ejection time index and Q-S2 were positively correlated at the P = 0.01 level. This correlation probably results from a subjective bias of selecting the component of the second sound that is closest to the incisura in reading the charts manually. There was no relation between preejection period and heart rate. Therefore no linear regression formula was calculated for the former variable. ICTc was calculated for comparison by two methods: (1) from leg of the upstroke of the apex cardiogram to leg of the upstroke of the carotid pulse corrected for pulse transmission time, and (2) (leg of the apex cardiogram to SZ) minus left ventricular ejection time. The results indicated that the first method showed less scatter and a lower standard deviation. Thereafter, the first method was used routinely.
TABLE
TECHNHXIES-ZONERAfCH
ii
Comparison
of Manual Results with Results Obtained
Variable+
QSzl LVETI PEP ICTc EMI S&2 PEP/LVET DA/DT
with Computer
System (msec)
Regression Equation
Manual Results
Computer Results
520.4- 1.79(HR) (no. = 93; r = -0.68) 417.5- 1.59(HR) (no. = 93; r = -0.67) Not significant (no. = 93; r = -0.11) Not significant (no. = 93; r = -0.11) Not significant (no. = 93; r = -0.15) 435.71.58{HR) (no. = 93; r = -0.65) Not significant (no. = 93; r = -0.16) Not significant (no. = 93; r = -0.09)
52O.Ozt 20.8
518.7-11 16.6
417.orf
19.4
414.0*
88.51
16.9
t Value
Probability
hl.3
0.43
P >0.50
15.7
+3.0
1.05
P <0.30
88.1&
12.9
+0.4
0.17
P >0.50
65.9zk 14.8
66.4zt
12.6
-0.5
0.23
P 20.50
24.11
24.5zt
4.3
-0.4
0.44
P >0.50
16.5
-1.8
0.61
P >0.50
+0.004
0.42
P >a.50
7.2
435.2120.2
437.0&
0.291&
0.287zk 0.55
.I....
.064
26.1
+ 13.1
Difference
...
...
a..
*Mean pulse transmission time was 28.5 msec. DA/DT = quantitative apex cardiogram; EMI = electromechanical interval; ICTc = isovolumic contraction time corrected for pulse transmission; LVETI = left ventricular ejection time index: PEP = preejection period; PEP/LVET = ratio of preejection Period to left ventricular ejection time: Q&l = electromechanical systole index; S1-S2 = mechanical systole.
May 1974
The Amerkan
Joemel of CARDIOLOGY
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COMPUTERZED
SYSTEM FOR NONINVASIVE
TECWKMS-ZBNeRAKlH
minimal effect on its duration.24 The same is true for isovolumic contraction time. The linear regression equation for left ventricular ejection time obtained by us is similar to that found by Weissler et a1.7 Isovolumic contraction time calculated from the leg of the upstroke of the apex cardiogram to the leg of the carotid upstroke is easily identifiable from simultaneous recordings of the apex cardiogram and carotid pulse. The beginning of the ejection period could not be calculated from the apex cardiogram alone by conventional methods of calculation, since it is difficult to identify the beginning of the ejection period that occurs before the E point of the apex cardiogram.8 Instead, the real beginning of the ejection period calculated from the upstroke of the apex cardiogram alone was obtained only by computer. DA/DT identified a fraction of the preejection period, corresponding to the upstroke of the first derivative of the apex cardiogram and considered to be similar to the first derivative of the left ventricular pressure.25 The magnitude of the first derivative of the apex cardiogram has been considered to be proportional to the velocity of motion of the left ventricular wall and related to the functional status of the myocardium.26 The interval between the onset of ventricular depolarization and the preejection peak of the first derivative of left ventricular pressure, suggested by Mason et a1.27as an index of left ventricular function, has been correlated by Vetter et a1.28 with the interval between the onset of ventricular depolarization and the preejection peak of the first derivative of the apex cardiogram. Statistically significant correlations were obtained with ejection fraction, left ventricular end-diastolic pressure and left ventricular end-diastolic volume. The data obtained by this group support the use of quantitative apex cardiography for screening of serial clinical studies of left ventricular function. Advantages of Computerized System
Computing systems have been used for noninvasive techniques in the past by Freis and Kyle,2g who recorded the carotid and brachial pulses on magnetic tape, plotted the curves with a computer and then manually identified the time intervals. Eddleman30 analyzed the precordial pulsations by normalized plots of kinetocardiograms. Golde and Burstin31 manually calculated systolic time intervals in normal children, stored the obtained data on magnetic tape and used an IBM 360-50 computer for statistical analysis. Our computerized system for the first time eliminates any manual identification for calculations of variables of systolic time intervals. The advantages of fast and accurate calculations are evident. Evaluation of left ventricular perfor-
ET AL.
mance, which requires the use of many variables and is difficult to measure manually, can easily be calculated by the computing system. DA/DT as an expression of quantitative apex cardiography, for evaluation of left ventricular function, could be identified by the computer from the apex cardiogram alone. Graphic computer output at a ratio of more than 1,000 msec permits analysis of individual heart sound components and timing relations. Printed computer output provides computation for up to 10 cardiac cycles and performs automatic correction for rate-dependent variables. Reliable data obtained by conventional high fidelity phonocardiographic equipment are almost identical to those obtained by the computing system (Table II) and confirms the validity of ratios and variables conventionally obtained by external measurements of systolic time intervals. The hemodynamic factors involved in determining the systolic time intervals are now better recognized. Simultaneous measurements of intracardiac dynamics have demonstrated close parallelism between direct and indirect measurements32 of systolic time intervals. Externally recorded systolic time intervals are used on a large scale for the evaluation of left ventricular performance in man in acute and chronic cardiovascular disease. The use of the computerized system offers several distinct advantages over the present conventional recording system. By following precisely defined algorithms and computing first derivatives, the computer eliminates subjective variability in the identification of events in the cardiac cycle. This is particularly important in the identification of muffled heart sounds and slurred pulse wave upstrokes. The significant increase in accuracy (1 msec compared to 5 msec with conventional recordings) obtainable with the computer system should reduce the present variances and overlapping results obtained from the calculation of systolic time intervals calculated by different observers. Individual position assessment of the morphologic aspects of the tracing is facilitated by the high graphic output speed used in the display of the tracings and by the printed computation covering 10 heart cycles. The greatest potential advantage of the computerized system lies in its ability to calculate quickly more sophisticated variables related to contractility from externally measured tracings. The use of these variables, difficult to measure manually, could lead to a better evaluation of left ventricular performance. Acknowledgment We thank Mr. Floyd Jackson for his assistance with photography, Miss Ada Fantroy for her technical assistance and Mrs. Karen Franklin for her secretarial assistance.
References 1. Non-InvasiveMethods in Cardiology (Zoneraich S. ed). Springfield, Ill., Charles C Thomas, in press 2. Zonerakh S, Zonerakh 0: Non-aggressive evaluation in coro-
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Volume 33
nary artery disease (abstr). Ann Intern Med 72:782. 1970 3. Zonerakh S, Zonarekh 0, Douglas Al: Physical Signs in Coronary Artery Disease Documented Graphically. New York, Case
COMPUTERIZED SYSTEM FOR NONINVASIVE
the Printer, 1968 4. Zonerakh S, Zonerakh 0: Alternation in jugular pulse. Ann Intern Med 78:610. 1973 5. Zonerakh S, Zonerakh 0: Value of auscultation and phonoarteriography in detecting atherosclerotic involvement of the abdominal aorta and its branches. Am Heart 83:820-629, 1972 6. Perloff JK, Relchek N: Value and limitations of systolic time intervals (preejectiin period and ejection time) in patients with acute myocardial infarction. Circulation 45929-931, 1972 7. Welsster AM, Harris WS, Schoenfeld CD: Systolic time intervals in heart failure in man. Circulation 37:149-X9, 1968 8. Kumar S, Spodlck DH: Study of the mechanical events of the left ventricle by atraumatic techniques: comparison of methods of measurement and their significance. Am Heart J 80:401413,197o 9. Fabian J, Epstein EJ, Co&shed N: Duration of phases of left ventricular systole using indirect methods, Br Heart J 34:847881, 1972 10. Dlamant B, Kllllp T: Indirect assessment of left ventricular performance in acute myocardial infarction. Circulation 42:579592, 1970 11. Jaln SR, Llndahl J: Apexcardiogram and systolic time intervals in acute myocardial infarction. Br Heart J 33:578-584, 1971 12. Hamosh P, Cohn JN, Engelman K, et al: Systolic time intervals and left ventricular function in acute myocardial infarction. Circulation 45~375-380, 1972 13. McConahay DR, Martin CM, Cheltlln MD: Resting and exercise systolic time intervals. Circulation 45:592-60 1, 1972 14. Chalthlraphan S, Goldberg 0: Systolic time intervals, relation to atrial contraction and leg elevation in patients with transvenous pacemakers and fixed rate pacing. Chest 62:720-727, 1972 15. Tavel ME, Baugh Do, Felgenbaum H, et al: Left ventricular ejection time in atrial fibrillation. Circulation 46:744-752, 1972 16. Hdkklla J, Luomanmakl K, Pyorala I: Serial observations on left ventricular dysfunction in acute myocardial infarction. Circulation 44:343-354, 197 1 17. Hodges M, Halpern B, Frleslnger GC, et al: Left ventricular PEP and ejection time in patients with acute myocardial infarction. Circulation 45:933-942, 1972 18. Whltsett TL, Oddberg LI: Effects of levodopa on systolic pre-
19.
20.
21.
22. 23. 24.
25.
28. 27.
28. 29. 30.
31. 32.
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TECHNIQUES-ZONERAlCH
ET AL.
ejection period, blood pressure and heart rate during acute and chronic treatment of Parkinson& disease. Circulation 45:94106, 1972 Austin TW, Ahuya SP, Coughner DR: Atraumatic study of left ventricular events following acute myocardial infarction. Am J Cardiol29:745-748, 1972 Llndqulst VAY, Spangler RD, Blount So: A comparison between the effects of dynamic and isometric exercise as evaluated by the systolic time intervals in man. Am Heart J 82:227236, 1973 Welssler AM, Harris WS, Schoenfeld CD: Bedside techniques for the evaluation of ventricular function in man. Am J Cardiil 23~577-583, 1969 Metzger CC, Chough CB, Koretz FW, et al: The isovolumic contraction time. Am J Cardiil 25:434-442, 1970 Abbott AJ: The fidelity of the externally recorded human pulse. Am J Med Sci 258:40-5 1, 1969 Martin CE, Shaver JA, Leonard JL: Physical signs, apexcardiography, phonocardiography, and systolic time intervals in angina pectoris. Circulation 46:1098-l 114, 1972 Reale A: Evaluation of the contractile state of the human heart from first derivative of the apexcardiogram. Circulation 36: 933-941, 1967 Johnston FD, Dvery DC: Vibrations of low frequency over the precordium. Circulation 3:579-588, 1951 Mason DT, Sonnenblick EH, Ross J, et al: Time to peak Dp/dt: a useful measurement for evaluating the contractile state of the human heart (abstr). Circulation 32: Suppl ll:ll-145, 1985 Vetter WR, Sullivan RW, Hyatt KH: Assessment of quantitative apexcardiography. Am J Cardiol 29:867-671, 1972 Frels ED, Kyle MC: Computer analysis of carotid and brachiil pulse waves. Am J Cardiol 22:691-695, 1988 Eddleman EE, Jr: Inspection and palpation of the precordium. In The Heart (Hurst JW. Logue RB, ed), second edition. McGrawHill, New York, 1970, p 192-207 Golde D, Burstln L: Systolic phases of the cardiac cycle in children. Circulation 42:1029-1035, 1970 Martln CE, Shaver JA, Thompson ME, et al: Direct correlation of external systolic time intervals with internal indices of left ventricular function in man. Circulation 44:419-431, 1971
The American Journal ot CARDIOLOGY
Volume 33
649
Computerized System for Noninvasive Techniques I. Its
Value for Systolic Time Intervals
SAMUEL ZONERAICH, MD, FACC OLGA ZONERAICH, MD JOHN RODENRYS, MS Jamaica, Queens, and Stony Brook,
New York
From the Department of Medicine, Division of Cardiology, Queens Hospital Center, Long Island Jewish-Hillside Medical Center, Clinical Campus of the School of Medicine, State University of New York at Stony Brook, Stony Brook, N. Y. Manuscript accepted August 9. 1973. Address for reprints: Samuel Zoneraich. MD, Division of Cardiology, Queens Hospital Center, 82-88 164 St., Jamaica, Queens. N. Y. 11432.
A total computerized system for the study of the noninvasive techniques and especially for external systolic time intervals is presented. Heart rate, left ventricular ejection time index (LVETI), Q-S2 I (electromechanical index), preejection period (PEP), PEP/LVET ratio, isovolumic contraction time corrected for pulse transmission (ICTc), electromechanical interval (EMI), mechanical systole (St-Sp), DA/D1 (quantitative apex cardiogram) and heart sounds were calculated from simultaneous recordings of electrocardiogram, carotid pulse and apex cardiogram by a multichannel, multifilter Cambridge MCIV phonocardiograph and by a CVAI94 unit MDS computer program. A parallel study of these variables in 100 healthy persons by conventionat manual calculations made from the Cambridge recordings and by the CVA/94 MDS computer system revealed identical results. The computerized system could more rapidly and accurately calculate many variables for systolic time intervals, thus offering the possibility for better evaluation of left ventricular function. Regression equations in relation to heart rate were found only for O-Sn = 520.4 - 1.79 heart rate; LVET = 417.5 - 1.59 heart rate; and S1-S1 = 435.7 - 1.58 heart rate. IClc and EMI differences were negatively correlated at the P = 0.001 level. LVETI and D-Si correlated positively at the P = 0.01 level. DA/D1 reflecting quantitative apex cardiography could be calculated only by computer.
An extensive search for the potential usefulness of noninvasive methods in cardiology has been made in this laboratory’-5 and others during the last few years. Data have been accumulated on the duration of various phases of cardiac systole by using simultaneous external polycardiographic techniques. The durations of these phases, when studied by noninvasive methods, were found to be altered in many abnormal cardiac states. The use of systolic time intervals has been criticized because the regression equation in relation to heart rate varies widely in normal control subjects as studied by various groups and because there are problems of methodology and experimental design.6 A review of normal values for systolic time intervals compiled from 14 original papers7-20 indicates the wide range of these variables in normal subjects (Table I). The purpose of this study was (1) to determine the usefulness of a rapid computer analysis for the measurement of systolic time intervals; (2) to eliminate human error in a parallel study by comparing the data obtained from conventional high fidelity equipment and manual measurements, with those obtained by a computerized system; (3) to calculate, through a computerized system, a large number of known variables, for a better and broader evaluation of left ventricular function; and (4) to compute new variables, not obtainable by conventional means.
May 1974
The American Journal of CARDIOLOGY
Volume 33
643
COMPUTERKED
SYSTEM
FOR
NDNINVASIVB
TBCflNtQUES-ZONERACH
ET AL.
TABLE I Normal
Values
for Systolic
Time
Intervals
in 14 Studies*
Subjects Authors
(no.)
Q-S,
et al.’
211
(M) QS, = 2.1 HR + 546 rt 14 (F) QS,= 2.0 H R + 549 It 14
Weissler
Kumar
& Spodick8
50
Fabian
et al.9
50
Diamant Jain
& Killiplo
& LindahI”
Hamosh
et al.l2
McConahay
et al.13
Chaitiraphan Goldberg” Tavel
81
et al.16
0.49 set - 0.0017 X HR + 0.017
0.11 set x HRI
0.38 set - 0.0013 x HR rt 0.019
12
539 - 2.00 HR f. 15.9
42
-0.020 x HR + 0.522
-0.0004 x HR + 0.0126
-0.0016 0.394
33
Weissler
Weissler
. .
et al.
0.0003 0.015
et al.
ICT
EMI
PTT (msec)
...
...
...
...
22 + 9.8
...
(F) 1.6 H R + 418 ZE 10
35
1.41 HR zt
x HR +
... 464 - 1.49 HRfl6 ...
NC 70.9 f. 15.8 70 It 9.5
...
23
0.052 set - 0.0002 X HR +z 0.015
...
...
. .
...
...
...
...
. 9.
...
...
...
...
Weissler
et al.
...
...
...
Weissler
et al.
...
...
...
...
27
...
Identical to Weissler et al.
...
...
...
...
65-0.17HRf12
...
...
. 9.
...
...
40
et aLM
1.7 HR + 413
S,-8)
f 10
389 13
et aLI7
Lindquist
+ 11
(M)
126 - 0.34 H R f 12
Hodges
& Goldberg18
+ 13 0.4 HR + 133
-159 + 503 HR ZIz 14
139
et al.‘9
0.4 HR + 131
376 - 1.2 HR f 12
et aLI
Austin
LVET
NC
Heikkila
Whitsett
PEP
Weissler
et al.
2.33 HR + Q-S,
...
...
10
...
21
Weissler
et al.
Weissler
NC HR 90 f
-2.22 HR + -443.7
. .
2.3
Weissler
...
et al.
et al.
..
-1.85 HR + 502 f 16
-0.44 rt9
HR + 117
-1.42 HR + 385 =!z 12
456 - 1.8 HRf 15
Diamant
& Killip
...
...
...
..a
52.4 f
14.9
24.7 z+z 10.2
...
..
-0.07
HR + 32
..
. ..
f 10
Because of different characteristics of phonocardiographic machines, several groups established their own normal values. Other groups used formulas established by one or two investigators. EMI = electromechanical interval: HR = heart rate; ICT = isovolumic contraction time; LVET = left ventricular ejection time; NC = no correlation with heart rate; PEP = preejection period; PTT = pulse transmission time; Q-S, = electromechanical systole; S1-S2 = mechanical systole.
seconds were used to record the apex cardiogram and carotid pulse (funnel shape pick-up). A Cambridge 2100-4 microphone was used to record the phonocardiogram. The paper speed was 100 mm/set. A Cambridge l-206, five lead cable was used to record lead II of the electrocardiogram. The MDS system utilized a Hewlett-Packard 21050 to record the carotid pulse and a single direct contact microphone 21050 A to record the apex cardiogram and phonocardiogram. A Hewlett-Packard 14056-B, three lead electrocardiographic cable was used to record lead II. After verification of proper signal placement, using the oscilloscope monitor on the CVAl94 cart, a simultaneous 10 second recording was made on the CVAl94 strip chart and on the magnetic tape using a frequency modulation (FM) recording technique.
Material and Methods One hundred ambulatory, nonhospitalized persons, ranging in age from 17 to 62 years (mean 36.6), with no history of heart disease were included in this study. The number of men and women was almost equal. All subjects had a normal history, normal cardiovascular system on clinical examination, normal electrocardiogram, a systolic pressure of 140 mm Hg or less and a diastolic pressure of 90 or less. They were receiving no medication, The studies were performed at approximately the same time (early in the morning). The subjects were placed in the left lateral decubitus. During held expiration a 10 second recording was made of simultaneous apex cardiogram, carotid pulse tracing, phonocardiogram and lead II electrocardiogram with a Cambridge multichannel MCIV recorder and immediately after with the Medical Data Systems (MDS) CVA/94 unit (Medical Data Systems, Inc., San Diego, Calif.) (Fig. 1). l-665 Cambridge pulse transducers with a time constant of 3.5
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Intervals The following variables were computed with the CVAl94 computer program and, conventionally, by MCIV Cambridge recording:
33
CDh&WERlZED
FIGURE 1. Schematic drawing of flow of patient signals during study using recordings and data processing performed by the Cambridge recorder and conventional calculation and by the CVA/94 unit MDS computer system. ACG = apex cardiogram, CPP = carotid pulse; ECG = electrocardiogram; PCG = phonocardiogram.
SYSTEM FDR NDNWWASIVE
TECHNlQlJES-ZDNERACH
computer
a”alySlS
STI comp”tat,ms
cornpu,er O”tputrwxOfllnlplotS
\
ET AL.
heart sound
~~mp”,at,~n
V
Heart rate: R-R interval (beats/min). Left ventricular ejection time index (LVETZ): carotid upstroke to trough of carotid incisura, corrected for heart rate. Electromechanical systole index (Q-S, I): Q wave of the electrocardiogram to the aortic component of the second heart sound, corrected for heart rate. Preejection period (PEP): Q wave to leg of upstroke of the carotid pulse, corrected for pulse transmission time. Electromechanical interval (EMZ): Q wave to upstroke of apex cardiogram. Zsovolumic contraction time, corrected for pulse transmission time (ICTc): (a) leg of upstroke of apex cardiogram to leg of upstroke of carotid pulse, corrected for pulse transmission time; (b) (leg of apex cardiogram to second heart sound) minus left ventricular ejection time. PEP/LVET: ratio of preejection period to left ventricular ejection time. Quantitative apex cardiogram (DAIDT) (calculated only by computer): ratio of the relative excursion of the apex cardiogram from leg of upstroke to the point of maximal slope (rate of change of apex cardiogram) divided by the interval between the Q wave of the electrocardiogram and the time of maximal slope.
Manual Analysis Manual calculations of the systolic time intervals obtained with the Cambridge MCIV recording were read to the nearest 5 msec for 10 consecutive cycles. The rate-dependent raw values were corrected for heart rate and then averaged to obtain a representative value. Raw values that were not rate-dependent were directly averaged to obtain a representative value.
back into the CDC 1700 computer through an analog tape recorder and the signals digitized at the rate of 1,000 times/ set for 10 seconds. After analog to digital conversion, an interactive graphics monitor was used to display the digital signals. A check was made at this time for artifactual or missing signals. After verification of satisfactory signals, the patient’s signals were written on digital magnetic tape. The CVA/94 computer program analysis was performed on a CDC 1700 computer using the digital magnetic tape that was previously written. During the processing, 10 consecutive cardiac cycles were analyzed. The computer performed two basic functions; detection of heart sounds and computation of systolic time intervals. During the computer analysis, all rate-dependent intervals were converted into their respective indexes. At the completion of processing, a 45 line printer and a computer output microfilm (C.O.M.) tape were generated. In addition, 700 items of information on each patient were printed on the line printer for the basic reference file. The C.O.M. tape was taken to a Datagraphic X4020 C.O.M. computer which produced graphs of the original signals of the patients (Fig. 2 and 3) with computer-generated annotations. These plots are for physician review of configuration and computer accuracy. The graphs are stored on microfilm and 11 by 11 bond paper. Normal values for the interval are printed by the computer for comparison. The computer program also provides data on the time of occurrence of the following heart sounds: systolic clicks, aortic component of the second heart sound (As), opening snap, third (Ss) and fourth (Sd) heart sounds and the mitral component of the first heart sound @I).
Computer Processing
Comparison and Statistical Analysis
The recordings made on the magnetic tape were processed by computer in two stages: (1) analog to digital conversion, and (2) CVA/94 computer program analysis. The analog to digital conversion was performed on a CDC 1700 computer. The analog tape cassettes were played
During the statistical comparison, the data from the Cambridge tracings and the Medical Data Systems computer program were assumed to be from two different populations. A Student t test for the differences between the means of two variables was performed. A correlation study,
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coMpuTERuzD
SYSTEM FOR NQNINVASIVE
lW%WQUES--2ONEFtAtCl.l
El
AL.
FIGURE 2. Computer graphs of the original patient signals. From top to bottom: electrocardiogram. carotid pulse tracing, apex cardiogram and phonocardiiram. Numbers at top identify patients code number, hospital code number and tape file Index.
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cardiac cycle. The figures are registered on the chart. From top to bottom: electrocardiogram, carotid pulse tracing, apex cardiogram and phonocardiogram. The pattent’s code nufffber, hospital code number, taupe file index and both the first and second heart sounds are indicated. Values are shown for cycle number, heart fate, pfeejection period, true isovolumic contraction time, isovolumic contractlon time and left ventricular ejection time (LVET).
CmZED
SYSTEM FOR NDNINVASIVE
ET AL.
Discussion Our study clearly demonstrates that many of the disadvan~ges of using systolic time intervals could be avoided by using better techniques of recording and calculating these intervals. Our approach for recording multiple variables is based on theoretical and practical considerations indicating that no single measure has proved to be of unchallenged superiority in evaluating left ventricular function and that the interpretation of results obtained by any method must be qualified by recognition of the limitations of the technique. It is important to realize that the early vibrations of the first heart sound21,22 are occasionally difficult to identify for calculation of isovolumic contraction time, that the latter may increase the value of preejection period as a measure of left ventricular performance and, finally, that newer variables such as electromechanical interval and DA/DT may reflect significant events in the cardiac cycle. Use of the apex cardiogram for the calculation of isovolumic contraction time diminishes the wide variability encountered in the normal population when measurements for this variable are based on the identification of a high vibration in the first heart sound. Recording of the apex cardiogram requires minimal experience. Poor or unobtainable tracings due to obesity, chronic lung disease or other causes occur in less than 10 percent of recordings in our experience. Minimal arterial distortion resulting from filtering and information gain are occasionally encountered in obese subjects when the arterial pulse is recorded.23 Our data indicate that the preejection period could not be corrected for heart rate, since heart rate has a
using the null hypothesis, was also performed to determine the relation between the differences of the variables.
ResuRs As shown in Table II, none of the differences between the manual and the computer results were significant (6 values were at the P = 0.50 level and 1 was at the P = 0.30 level), indicating that the computer system was almost duplicating the results obtained by manual, conventional calculation of the Cambridge recorded signals. The results indicate only two significant relations among the differences. Differences for isovolumic contraction time, corrected for pulse transmission time (ICTc), correlated negatively with each other at the P = 0.001 level. This is an expected finding, since a prolonged ICTc interval will shorten the electromechanical interval and vice versa. Left ventricular ejection time index and Q-S2 were positively correlated at the P = 0.01 level. This correlation probably results from a subjective bias of selecting the component of the second sound that is closest to the incisura in reading the charts manually. There was no relation between preejection period and heart rate. Therefore no linear regression formula was calculated for the former variable. ICTc was calculated for comparison by two methods: (1) from leg of the upstroke of the apex cardiogram to leg of the upstroke of the carotid pulse corrected for pulse transmission time, and (2) (leg of the apex cardiogram to SZ) minus left ventricular ejection time. The results indicated that the first method showed less scatter and a lower standard deviation. Thereafter, the first method was used routinely.
TABLE
TECHNHXIES-ZONERAfCH
ii
Comparison
of Manual Results with Results Obtained
Variable+
QSzl LVETI PEP ICTc EMI S&2 PEP/LVET DA/DT
with Computer
System (msec)
Regression Equation
Manual Results
Computer Results
520.4- 1.79(HR) (no. = 93; r = -0.68) 417.5- 1.59(HR) (no. = 93; r = -0.67) Not significant (no. = 93; r = -0.11) Not significant (no. = 93; r = -0.11) Not significant (no. = 93; r = -0.15) 435.71.58{HR) (no. = 93; r = -0.65) Not significant (no. = 93; r = -0.16) Not significant (no. = 93; r = -0.09)
52O.Ozt 20.8
518.7-11 16.6
417.orf
19.4
414.0*
88.51
16.9
t Value
Probability
hl.3
0.43
P >0.50
15.7
+3.0
1.05
P <0.30
88.1&
12.9
+0.4
0.17
P >0.50
65.9zk 14.8
66.4zt
12.6
-0.5
0.23
P 20.50
24.11
24.5zt
4.3
-0.4
0.44
P >0.50
16.5
-1.8
0.61
P >0.50
+0.004
0.42
P >a.50
7.2
435.2120.2
437.0&
0.291&
0.287zk 0.55
.I....
.064
26.1
+ 13.1
Difference
...
...
a..
*Mean pulse transmission time was 28.5 msec. DA/DT = quantitative apex cardiogram; EMI = electromechanical interval; ICTc = isovolumic contraction time corrected for pulse transmission; LVETI = left ventricular ejection time index: PEP = preejection period; PEP/LVET = ratio of preejection Period to left ventricular ejection time: Q&l = electromechanical systole index; S1-S2 = mechanical systole.
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COMPUTERZED
SYSTEM FOR NONINVASIVE
TECWKMS-ZBNeRAKlH
minimal effect on its duration.24 The same is true for isovolumic contraction time. The linear regression equation for left ventricular ejection time obtained by us is similar to that found by Weissler et a1.7 Isovolumic contraction time calculated from the leg of the upstroke of the apex cardiogram to the leg of the carotid upstroke is easily identifiable from simultaneous recordings of the apex cardiogram and carotid pulse. The beginning of the ejection period could not be calculated from the apex cardiogram alone by conventional methods of calculation, since it is difficult to identify the beginning of the ejection period that occurs before the E point of the apex cardiogram.8 Instead, the real beginning of the ejection period calculated from the upstroke of the apex cardiogram alone was obtained only by computer. DA/DT identified a fraction of the preejection period, corresponding to the upstroke of the first derivative of the apex cardiogram and considered to be similar to the first derivative of the left ventricular pressure.25 The magnitude of the first derivative of the apex cardiogram has been considered to be proportional to the velocity of motion of the left ventricular wall and related to the functional status of the myocardium.26 The interval between the onset of ventricular depolarization and the preejection peak of the first derivative of left ventricular pressure, suggested by Mason et a1.27as an index of left ventricular function, has been correlated by Vetter et a1.28 with the interval between the onset of ventricular depolarization and the preejection peak of the first derivative of the apex cardiogram. Statistically significant correlations were obtained with ejection fraction, left ventricular end-diastolic pressure and left ventricular end-diastolic volume. The data obtained by this group support the use of quantitative apex cardiography for screening of serial clinical studies of left ventricular function. Advantages of Computerized System
Computing systems have been used for noninvasive techniques in the past by Freis and Kyle,2g who recorded the carotid and brachial pulses on magnetic tape, plotted the curves with a computer and then manually identified the time intervals. Eddleman30 analyzed the precordial pulsations by normalized plots of kinetocardiograms. Golde and Burstin31 manually calculated systolic time intervals in normal children, stored the obtained data on magnetic tape and used an IBM 360-50 computer for statistical analysis. Our computerized system for the first time eliminates any manual identification for calculations of variables of systolic time intervals. The advantages of fast and accurate calculations are evident. Evaluation of left ventricular perfor-
ET AL.
mance, which requires the use of many variables and is difficult to measure manually, can easily be calculated by the computing system. DA/DT as an expression of quantitative apex cardiography, for evaluation of left ventricular function, could be identified by the computer from the apex cardiogram alone. Graphic computer output at a ratio of more than 1,000 msec permits analysis of individual heart sound components and timing relations. Printed computer output provides computation for up to 10 cardiac cycles and performs automatic correction for rate-dependent variables. Reliable data obtained by conventional high fidelity phonocardiographic equipment are almost identical to those obtained by the computing system (Table II) and confirms the validity of ratios and variables conventionally obtained by external measurements of systolic time intervals. The hemodynamic factors involved in determining the systolic time intervals are now better recognized. Simultaneous measurements of intracardiac dynamics have demonstrated close parallelism between direct and indirect measurements32 of systolic time intervals. Externally recorded systolic time intervals are used on a large scale for the evaluation of left ventricular performance in man in acute and chronic cardiovascular disease. The use of the computerized system offers several distinct advantages over the present conventional recording system. By following precisely defined algorithms and computing first derivatives, the computer eliminates subjective variability in the identification of events in the cardiac cycle. This is particularly important in the identification of muffled heart sounds and slurred pulse wave upstrokes. The significant increase in accuracy (1 msec compared to 5 msec with conventional recordings) obtainable with the computer system should reduce the present variances and overlapping results obtained from the calculation of systolic time intervals calculated by different observers. Individual position assessment of the morphologic aspects of the tracing is facilitated by the high graphic output speed used in the display of the tracings and by the printed computation covering 10 heart cycles. The greatest potential advantage of the computerized system lies in its ability to calculate quickly more sophisticated variables related to contractility from externally measured tracings. The use of these variables, difficult to measure manually, could lead to a better evaluation of left ventricular performance. Acknowledgment We thank Mr. Floyd Jackson for his assistance with photography, Miss Ada Fantroy for her technical assistance and Mrs. Karen Franklin for her secretarial assistance.
References 1. Non-InvasiveMethods in Cardiology (Zoneraich S. ed). Springfield, Ill., Charles C Thomas, in press 2. Zonerakh S, Zonerakh 0: Non-aggressive evaluation in coro-
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nary artery disease (abstr). Ann Intern Med 72:782. 1970 3. Zonerakh S, Zonarekh 0, Douglas Al: Physical Signs in Coronary Artery Disease Documented Graphically. New York, Case
COMPUTERIZED SYSTEM FOR NONINVASIVE
the Printer, 1968 4. Zonerakh S, Zonerakh 0: Alternation in jugular pulse. Ann Intern Med 78:610. 1973 5. Zonerakh S, Zonerakh 0: Value of auscultation and phonoarteriography in detecting atherosclerotic involvement of the abdominal aorta and its branches. Am Heart 83:820-629, 1972 6. Perloff JK, Relchek N: Value and limitations of systolic time intervals (preejectiin period and ejection time) in patients with acute myocardial infarction. Circulation 45929-931, 1972 7. Welsster AM, Harris WS, Schoenfeld CD: Systolic time intervals in heart failure in man. Circulation 37:149-X9, 1968 8. Kumar S, Spodlck DH: Study of the mechanical events of the left ventricle by atraumatic techniques: comparison of methods of measurement and their significance. Am Heart J 80:401413,197o 9. Fabian J, Epstein EJ, Co&shed N: Duration of phases of left ventricular systole using indirect methods, Br Heart J 34:847881, 1972 10. Dlamant B, Kllllp T: Indirect assessment of left ventricular performance in acute myocardial infarction. Circulation 42:579592, 1970 11. Jaln SR, Llndahl J: Apexcardiogram and systolic time intervals in acute myocardial infarction. Br Heart J 33:578-584, 1971 12. Hamosh P, Cohn JN, Engelman K, et al: Systolic time intervals and left ventricular function in acute myocardial infarction. Circulation 45~375-380, 1972 13. McConahay DR, Martin CM, Cheltlln MD: Resting and exercise systolic time intervals. Circulation 45:592-60 1, 1972 14. Chalthlraphan S, Goldberg 0: Systolic time intervals, relation to atrial contraction and leg elevation in patients with transvenous pacemakers and fixed rate pacing. Chest 62:720-727, 1972 15. Tavel ME, Baugh Do, Felgenbaum H, et al: Left ventricular ejection time in atrial fibrillation. Circulation 46:744-752, 1972 16. Hdkklla J, Luomanmakl K, Pyorala I: Serial observations on left ventricular dysfunction in acute myocardial infarction. Circulation 44:343-354, 197 1 17. Hodges M, Halpern B, Frleslnger GC, et al: Left ventricular PEP and ejection time in patients with acute myocardial infarction. Circulation 45:933-942, 1972 18. Whltsett TL, Oddberg LI: Effects of levodopa on systolic pre-
19.
20.
21.
22. 23. 24.
25.
28. 27.
28. 29. 30.
31. 32.
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ET AL.
ejection period, blood pressure and heart rate during acute and chronic treatment of Parkinson& disease. Circulation 45:94106, 1972 Austin TW, Ahuya SP, Coughner DR: Atraumatic study of left ventricular events following acute myocardial infarction. Am J Cardiol29:745-748, 1972 Llndqulst VAY, Spangler RD, Blount So: A comparison between the effects of dynamic and isometric exercise as evaluated by the systolic time intervals in man. Am Heart J 82:227236, 1973 Welssler AM, Harris WS, Schoenfeld CD: Bedside techniques for the evaluation of ventricular function in man. Am J Cardiil 23~577-583, 1969 Metzger CC, Chough CB, Koretz FW, et al: The isovolumic contraction time. Am J Cardiil 25:434-442, 1970 Abbott AJ: The fidelity of the externally recorded human pulse. Am J Med Sci 258:40-5 1, 1969 Martin CE, Shaver JA, Leonard JL: Physical signs, apexcardiography, phonocardiography, and systolic time intervals in angina pectoris. Circulation 46:1098-l 114, 1972 Reale A: Evaluation of the contractile state of the human heart from first derivative of the apexcardiogram. Circulation 36: 933-941, 1967 Johnston FD, Dvery DC: Vibrations of low frequency over the precordium. Circulation 3:579-588, 1951 Mason DT, Sonnenblick EH, Ross J, et al: Time to peak Dp/dt: a useful measurement for evaluating the contractile state of the human heart (abstr). Circulation 32: Suppl ll:ll-145, 1985 Vetter WR, Sullivan RW, Hyatt KH: Assessment of quantitative apexcardiography. Am J Cardiol 29:867-671, 1972 Frels ED, Kyle MC: Computer analysis of carotid and brachiil pulse waves. Am J Cardiol 22:691-695, 1988 Eddleman EE, Jr: Inspection and palpation of the precordium. In The Heart (Hurst JW. Logue RB, ed), second edition. McGrawHill, New York, 1970, p 192-207 Golde D, Burstln L: Systolic phases of the cardiac cycle in children. Circulation 42:1029-1035, 1970 Martln CE, Shaver JA, Thompson ME, et al: Direct correlation of external systolic time intervals with internal indices of left ventricular function in man. Circulation 44:419-431, 1971
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