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Isovolumetric contraction period of the left ventricle
lsovolumetric
contraction
Results
series
methods
in a normal of calculation
T
and comparison
by atraumatic
David H. Sfiodick, M.D.* Sudarshan Kumar, M.B.B.S., Boston, Muss.
of the
left
ventricle
of techniques
df.K.C.P.(Edin.)**
he heart is a muscular container in which changes in length and tension are associated with cyclic changes in the volume and pressure of its contents. Ventricular systole begins by setting up of tension and ends with completion of ejection. Initially, left ventricular wall tension is translated into movement and then to rising intracavitary pressure without change in volume. This period of isovolumetric contraction (IVCT) ends when intraventricular pressure exceeds aortic pressure; the resulting gradient opens the aortic valve and ejection of blood into the aorta quickly reduces ventricular volume. The significance of the IVCT can be summarized as follows: (1) IVCT is a direct expression of the sum of factors comprising “contractility”; especially the rate of rise of left ventricular pressure (dp/dt), i.e., the speed with which ventricular muscle can compress the blood to the ejection point; (2) IVCT reflects end-diastolic stretch and, secondarily, endFrom
period
diastolic volume; and (3) changes in IVCT reflect changes in electric, neural, metabolic, and pharmacological influences, as well as anatomic disruptions of the contractile elements. Because of its evident physiological importance, it would be desirable to have reliable methods of measuring IVCT in human beings which could also be repeated indefinitely without discomfort or danger. Indeed, atraumatic measurement of this interval might yield certain more reliable data than direct methods----particularly its changes in therapeutic and experimental situations-owing to two factors: (1) The patient cannot be “basal” during either chest operation or cardiovascular catheterization. These involve considerable physiological adaptation to the procedure itself, premeditation, and use of general or local anesthetic agents, as well as an indeterminate neural and catecholamine response to fear and apprehension, all of which affect the contractile characteristics
the Cardiology Division of the Medical Services, Lemuel Shattuck Hospital, Boston, Mass., and the Department of Medicine, Tufts University School of Medicine. investigation was supported by Grant NGR 22-012-006 from the National Aeronautics and Space Administration through the NASA Electronic Research Center. Cambridge, Mass. Received for publication Oct. 23, 1967. *Chief, Cardiology Division, Medical Services, Lemuel Shattuck Hospital; Assistant Professor of Medicine, Tufts ITniversity School of Medicine; Lecturer in Medicine. Boston TJniversity School of Medicine. **Assistant in Medicine, Tufts I‘niversity School of Medicine. Research Fellow, Cardiology, Lemuel Shattuck Hospital. This
498
American Heart Journal
Isovorumefric
of the myocardiunn. (2) Left ventricular movement appears to precede the onset of cavitary pressure rise (see below). Thus, depending on definition of IVCT, external detection of the very beginning of left ventricular contraction could be superior to catheter data. A variety of methods of atraumatically measuring I\,‘CT have been reported.l-7Ja-ifi We propose to compare these methods with the results of direct measurement and with each other and to suggest which may be the most reliable.
contraction
period of the
Material
and
left venfriclc
409
methods
A total of 50 normal active young men in a narrow age range (22 to 35 years) were studied. All had histories of total good health and had no physical, electrocardiographic, or roentgenological signs of heart or other disease. None was significantly obese and none was under any form of medication. 1Iultiple simultaneous cardiographic records were obtained on a Sanborn No. 56%100A eight-channel optical recorder at 75 mm. per second with the subject recumbent and in a relaxed expiratory apnea; these included : apexcardiogram (ACG) and phonocardiogram (with the use of the Sanborn No. 62-1500-Cl3 attachment and crystal microphone No. 374) and right external carotid arteriogram with the Sanborn No. TPS 10 pulse transducer. Calculations. IVCT was derived from these records by six different measurenlents1-7J-16(Fig. 1) : 1. The interval from the beginning of the ACG upstroke (ACGu) to that of the carotid (CAR) upstroke (CARu) : I\‘CT
= ACGu--CARu
(1)
2. i\Iethod Ko. 1 corrected for delay in pulse transmission time (PTT) of the central pulse to the carotid artery (see below) : IVCT
= ACGLI-(CARu
minus
PTT)
(2)
3. The interval between ACGu and the E-crest of the ACG: IVCT
= ACGu-E
(3)
4. The interval between the onset of the first rapid vibration of the first heart sound (“mitral sound”; In) and E: 4 5
IVCT
= 131-E
(1)
u PTT 2=!-#VT 6=5-
PTT
5. The interval between In ginning of the CARu: IVCT
Fig. 1. Indirect measurement of isovolumetric contraction period of the left ventricle; comparison of methods of calculation. Recordings, top to bottom: Electrocardiogram (ECG), carotid (CAR), apexcardiogram, apical phonocardiogram. Abbreviations: U, upstroke; In, incisure; E, E-point of ACG; rM, first rapid component of first heart sound; IIA, aortic component of second heart sound; PTT, pulse transmission time; I, 2, 3, 4, 5, 6, intervals used in calculations of isovolumetric contraction time (see text).
and be-
= I M-CARu
(5)
6. nIethod No. 5 corrected for PTT: IVCT
=
In-(CARu
minus
PTT)
(6)
PTT (“carotid delay time”) was measured by the interval between the aortic sound (11~) and the carotid incisura (CARI,) : PTT
= II*-CARr..
500
Table ment)
Spodick
rind h-zrmrrr
I. Isovolmvaetric
contmction
period
qf the
lqft ventricle
(comparison
of methods
of measure-
-___ 1 Kange Mean S.I). S.E.
(msec.)
70-120 94.1 13.9 2.1
I
2
I
JO-90 70.9 15.8
2.1
Results
Results of the various calculations are summarized in Table I. The mean values and ranges are rather disparate. JIethods 1 and 3 give means of 94.1 and 97.4 msec., respectively. Methods 4 and 5 yield means of 58.6 and 61.8 msec. Method 2 produces 70.9 msec. and method 6 39.0 msec. The narrowest ranges occur in methods 1 and 2, which also produce the least relative scatter (SD.). Discussion
The variability of results from different methods of measuring and computing IVCT, each based 011 formulas reported with confidence by some investigators,1-7z14-16 leads to an “embarrassment of choices,” which inevitably raises two questions: (1) How is the IVCT defined and does it require redefinition? (2) What criteria define a satisfactory indirect method of measurement? We shall attempt to answer these in reverse order and, in so doing, to arrive at a choice of the optimum method of determining IVCT. Dejinition of the II’CT. There is agreement that the end PO& of isovolumetric contraction is the onset of ejection. Since indirect recordings cannot be made from the ascending aorta, the time of onset of pressure rise (coincident with outward movement) of the carotid artery is used, with subtraction of the time for the pulse wave to travel from aorta to carotid-PTT. This delay appears to be the same at the onset as at the end of ejection7; indeed, it is precisely because of this relationship that left ventricular ejection
4
3 30-200 97.4 29.6 4.2
5
20-140 58.6 25.2 3.6
1
6 10-70 39.0 13.9 2.0
40-100 61.8 14.0 2.0
time is so reliably measured from carotid curves.8Fg Since the aortic sound (II*) is virtually coincident with aortic incisura, the PTT is the time between the appearance of 11~ and the carotid incisura (CARI,). For each subject, this interval can be deducted from the time of onset of the CARu to indicate the moment of ejection, and hence the endpoint of the IVCT. The exact beginning of isovolumetric contraction is not so easily establishedboth in physiological terms and in points of measurement. Thus, there are three potential isovolumetric contraction periods, each based on a different initial physiological event: 1.
THE
PERIOD
FROM
CLOSLTRE
OF
THE
This is the classic IVCT, measured internally by the time between crossing of the left ventricular pressure pulse curve first with the left atria1 curve and then with the aortic curve. Externally, this is approximated by the interval from I, to the ejection point. 2. THE PERIOD FROM THE BEGINNING OF MITRAL
VALVE
(‘.\VITARY
TO
EJECTION.
PRESSI!RE
RISE
To
EJECTION.
1%
this is measured from the onset of the left ventricular pressure curve (which precedes mitral closure) to its crossing of the aortic curve. Extevnully, this can be approximated by the interval from the initial ventricular deflection of the kinetocardiogram (KC(;) to the calculated ejection point. 3. THE PERIOD FROM THE EARLIEST DETEC‘Ttermlly,
ABLE
LEFT
VENTRICI‘LAR
MOVEMENT
TO
Internally, this cannot be measured. Extermlly, this is measured from the
EJECTION.
Isovolumetric
beginning of left ventricular motion to the calculated ejection point. The earliest detectable movement of left ventricular contraction (which precedes the rise of the pressure curve) is first registered by the ACGu; the initial ventricular deflection of the KCG occurs later. This relationship is reflected in the longer electromechanical lag of the KCG (mean = 38 msec.). Our shorter lag for the ACG of 22 nlsec.lo agrees with that of Levine’s group’ (21 tnsec. j. Reasons can be adduced for defining I\‘CT each way. It appears, however, that for purposes of external measurement, at the very least-and probably also in a physiological sense-it may be preferable to favor definition 3. The evidence for this may be summarized as follows: (1) left ventricular systole actually begins before the rise in left ventricular pressure; indeed, intramural pressure is well set up before cavitary pressure begins to rise,‘,“,” (2) this appears to be first detected by the ACG which usually rises before the pressure curve, and (3) the entire period of left ventricular contraction prior to ejection is encompassed. (Fortuitously, the necessarily longer period thus defined reduces the error inherent in measuring smaller intervals.) We shall return to these considerations later. With the foregoing in mind, it is necessar!. to define satisfactory indirect measurement before discussing our specific results. To be acceptable, any indirect method must fulfill three postulates: Postulates indirect
for acceptability of methods of measurement
I Results must duplicate or reasonably approximate those of any comparable direct method. II Calculations should be based on measurements reflecting the actual physiological events involved, i.e., if the numerical results are comparable with those of direct methods, this should not be accidental. III If more than one calculation fulfills Postulates I and II, the optimum method will be that for which the points measured can be established with greatest confidence in the technique of recording and identification. In view of these criteria, there are spe-
contmction
period of the left ventricle
50 1
cific objections to certain points used in various formulas for external derivation of IVCT. With regard to the endpoint of IVCT, the E-crest of the ACG is unsatisfactory, primarily because it does not appear to represent the actual onset of ejection2sy; indeed, its timing has a fair, though rather variable, correlation with the onset of the CARu-which must occur after the beginning of ejection. Indeed, left ventricular ejection times calculated from the E-crest to 11~ do not correlate satisfactorily with more accurate methods of measuring ejection time.“~8~gFinally, E often is a fairly broad summit and therefore susceptible to much more error of measurement than the relatively clear points at which the apex and carotid upstrokes depart. With regard to the heginning of IVCT, if this interval is defined as commencing with either the initial left ventricular movement (ACGu) or with the beginning of left ventricular pressure rise, it is clear that Ihf occurs much too late. Furthermore, even in terms of the classic IVCT beginning with mitral closure, I ~if remains a late event; it occurs after the crossing of the left ventricular and left atria1 pressure curves by as much as 40 nisec.,13 i.e., when the mitral valve is already closed and when there is already a relatively large V-A pressure gradient.13J4 Our results with each method of external measurement (Table I) may now be examined in the light of the foregoing discussion and in terms of the three postulates delineating satisfactory external measurements. Calcddion 5. IVCT = IbI-CARu = 61.8 f 14.0 msec. This result is extremely close to that of Braunwald and colleagues15 (61 f 12.1 msec.), for an IVCT beginning with the onset of left ventricular pressure rise (Definition 2 above). However, Postulate II obviously is not fulfilled since the result is accidental; the remarkable resemblance can be ascribed to a purely fortuitous cancellation of the delay in appearance of IM by that of CARu. Cdcdation 6. IVCT = IJI--(CARu PTT) = 39.0 =I= 13.9 msec. This should represent the classic IVCT noted in I>efinition 1; it agrees well with the 38 msec. mean of Holldack,“a which is based on essentially the same calculation. hIore-
502
Spodick and Kumar
over, if the mean of Tafur and associates’ for the same measurement (“PEC II”) is reduced by our mean PTT of 26 msec., a similar figure also results (41 msec.). Yet, other investigators report rather disparate mean values (Frank and Kinlaw6 49 msec., Raineri4 30 msec., and Merlen” 32.5 msec.). The discrepancy of approximately f 10 msec. probably represents variability in recording and measuring I&l--the first rapid vibration of the first heart sound; this means that Postulate III is difficult to fulfill for technical reasons. Even more important, Postulate II cannot be fulfilled since, as already noted, 101 is at best a late phenomenon. Indeed, on these grounds, it is difficult to understand the high figure reported only by Frank and Kinlaw. CaZcuZrAon 4. IVCT = Ill-E = 58.6 & 25.2 msec. This yields a result reasonably close to that of Calculation 5, probably because of the general correspondence of the timing of E to that of CARu noted by us9and others.2 It cannot be accepted, both because of the objections already cited for use of 101 and because E does not appear to represent true ejection (Postulate II not fulfilled). CaZczLZation3. IVCT = AC(;u-E = 97.4 f 29.6 msec. This result must also be rejected because of the objections cited for using E. Calculation 1. IVCT = ACGu-CARu = 94.1 =t 13.9 msec. This figure is quite close to that of Tafur and associates’ for the same measurement (102 msec.), but does not allow for PTT. Significantly, its mean of 94.1 msec. is very close to the 97.4 msec. of Calculation 3. This reflects the rough correspondence of E and CARu; the greater scatter in Calculation 3 (SD. twice that of Calculation 1) reflects the great variability of the E crest. Calculation 2. IVCT = ACGu-(CARu - PTT) = 70.9 + 15.8 msec. This result agrees well with that of Oreshkove2 for the same measurement (67 msec.). RIoreover, if our mean PTT of 26 msec. is subtracted from the result of Tafur and associates’ for Calculation 1 (above) this will yield 76 msec., which also approximates our result. The IVCT of Harrison and co-workers,7 measured from the “initial ventricular movement” of the kineto-
cardiogram to CARu - PTT, gave a mean value of about 63 msec. for men in the age group studied by us; since the end points are identical, the difference can be ascribed to the shorter electromechanical lag of the ACG as compared to the KCG. Calculation 2 appears to he the optimum method for measuring 11’CT based on the inclusive definition of this period. Indeed, Wiggers17 considered the period of rising left ventricular pressure in advance of mitral closure “so nearly isometric” as to warrant inclusion in the IVCT. By the same reasoning, the earliest contractile movement of the left ventricle, probably the result of the earliest intramural tension, is no less isometric and, therefore, cannot be ignored. Indeed, this relationship is clearly indicated in recent studies” which demonstrate a relatively steep increment in intramural left ventricular pressure well before cavitary pressure begins to rise. Conclusions
1. The IVCT is best defined as the total systolic period before ejection, at least for purposes of external measurement and probably also in a physiological sense. Specifically, it commences with the earliest left ventricular movement which appears to result from rising intramural tension in advance of the cavitary pressure rise. 2. The ACG records left ventricular motion before other external or internal methods; thus IVCT is best measured from the onset of its upstroke (ACGu) to the calculated ejection point. For external measurement, beginning ejection is calculated from the onset of the carotid pulse minus the time taken for pulse transmission from the ascending aorta. Our result for IVCT, therefore, is expressed as follows: IVCT = ACGu-(CARu
- PTT)
= 7F.9 * 15.8 msec.
3. Other methods of calculation appear to give widely divergent values for IVCT based both on the definition of IVCT used (and hence the points measured) and on the variability among investigators for results of the same methods. This variability appears to be due to the use of points of measurement which ma)
l’olnme
Sumber
76
Isovolumetric
4
not coincide with actual physiological events or which lack precise definition in recording. (An exception to this is the use by Harrison and co-workers’ of the “initial ventricular movement” of the IiCG which appears to approximate the beginning of left ventricular cavitary pressure. IVCT measured from this point to the calculated ejection point reflects a period which is susceptible to internal measurement; but it is shorter than that using the ACG, owing to the greater electromechanical lag of the IiCG and does not include the period of rising mural pressure.)
contraction
4.
5.
6.
7.
8.
Summury The isovolumetric contraction period of the left ventricle (IVCT) was measured atraumatically by six different cardiographic methods in 50 normal young men. IVCT has been redefined as the total period of left ventricular contraction prior to ejection-i.e., the period of left ventricular mural tension + the period of rising cavitary pressure. The ACG detects the earliest inception of left ventricular systole; both for accuracy of indirect measurement and physiologically the onset of its upstroke appears to be the beginning of isometric contraction. Our results for this period are 70.9 =t 15.8 msec., with the ejection point calculated by deduction of the PTT from the carotid upstroke. The results of other methods of calculation and other points of measurement are compared and discussed.
9. 10. 11.
12.
13.
14.
15.
REFERENCES 1. Tafur, The
E.,
Cohen,
L. S., and
Levine,
H.
D.:
normal apexcardiogram. Its temporal relationship to electrical, &oustic and mechanical cardiac events. Circulation 30:381. 1964. 2. Oreshkove, V.: Indirect measurement of isovolumetric contraction time on the basis of polygraphic tracing, Cardiologia 47:315, 1965. 2a. Holldack. K.: Cited bv Oreshkove? 3.
Benchimol,
A., and Dimond,
E. G.: The
normal
16.
17.
period of the left ventricle
503
and abnormal apexcardiogram. Its physiologic variation and its relation to intracardiac events, Am. J. Cardiol. 12:368, 1963. Raineri, A.: I1 cardiogramma apicale nella valutazione della dinamica cardiaca, Boll. Sot. Ital. Cardiol. 10:64, 1965. Merlen, J. F.: La phase isometrique de la systole ventriculaire, Actual. cardioangeiol. int. 14:119, 196.5. Frank, M. N., and Kinlaw, W. B.: Indirect contraction measurement of isovolumetric time and tension period in normal subjects, Am. J. Cardiol. 10:800, 1962. Harrison, T. R., Dixon, Ii., Russell, R. O., Jr., Bidwai. P. S.. and Coleman. H. N.: The relationship of age to the duration of contraction, ejection, and relaxation of the normal human heart, AM. HEART J. 67:189, 1964. Weissler, A. M., Peeler, R. G., and Roehll, \V. H.. lr.: Relationshios between left ventricular ejection time, stroke volume, and heart rate in normal individuals and patients with cardiovascular disease, A&f. HEART J. 62:367, 1961. Spodick, D. H., and Kumar, S.: Left ventricular ejection period, AM. HEART J. (in press). Spodick, D. H., and Kumar, S.: Electromechanical lag of the left ventricle. In preparation. Dieudonne, J. M.: Tissue-cavitary difference pressure of dog left ventricle, Am. J. Physiol. 213:101, 1967. Rios, J. C., and Massumi, R. A.: Correlation between the apex cardiogram and left ventricular pressure, Am. J. Cardiol. 15:647, 1965. DiBartolo, G., Nunez-Dey, D., Muiesan, G., MacCanon. D. M.. and Luisada. A. A.: Hemodynamic cdrrelates’of the first heart sound, -4m. J. Physiol. 201:888, 1961. Luisada, A. A., and Alimurung, N. M.: An encyclopedia of the cardiovascular system, in Luisada, A. A., editor: Cardiology, Vol. 1, New York, 1959, McGraw Hill Book Co., Inc., pp. 2-92. Braunwald, E., Fishman, A. P., and Cournand, A.: Time relationships of dynamic events in the cardiac chambers, pulmonary artery and aorta in man, Circulation Res. 4:100, 1956. Holldack, K.: Atlas und kurzgefasstes Lehrbuch der Phonokardiographie, Stuttgart, 1956, Thieme Verlag, p. 39. \&‘iggers, C. J.: Studies on the consecutive phases of the cardiac cycle. I. The duration of the consecutive phases of the cardiac cycle and the criteria for their precise determination, t\m. J. Physiol. 56:415, 1921.
contraction
Results
series
methods
in a normal of calculation
T
and comparison
by atraumatic
David H. Sfiodick, M.D.* Sudarshan Kumar, M.B.B.S., Boston, Muss.
of the
left
ventricle
of techniques
df.K.C.P.(Edin.)**
he heart is a muscular container in which changes in length and tension are associated with cyclic changes in the volume and pressure of its contents. Ventricular systole begins by setting up of tension and ends with completion of ejection. Initially, left ventricular wall tension is translated into movement and then to rising intracavitary pressure without change in volume. This period of isovolumetric contraction (IVCT) ends when intraventricular pressure exceeds aortic pressure; the resulting gradient opens the aortic valve and ejection of blood into the aorta quickly reduces ventricular volume. The significance of the IVCT can be summarized as follows: (1) IVCT is a direct expression of the sum of factors comprising “contractility”; especially the rate of rise of left ventricular pressure (dp/dt), i.e., the speed with which ventricular muscle can compress the blood to the ejection point; (2) IVCT reflects end-diastolic stretch and, secondarily, endFrom
period
diastolic volume; and (3) changes in IVCT reflect changes in electric, neural, metabolic, and pharmacological influences, as well as anatomic disruptions of the contractile elements. Because of its evident physiological importance, it would be desirable to have reliable methods of measuring IVCT in human beings which could also be repeated indefinitely without discomfort or danger. Indeed, atraumatic measurement of this interval might yield certain more reliable data than direct methods----particularly its changes in therapeutic and experimental situations-owing to two factors: (1) The patient cannot be “basal” during either chest operation or cardiovascular catheterization. These involve considerable physiological adaptation to the procedure itself, premeditation, and use of general or local anesthetic agents, as well as an indeterminate neural and catecholamine response to fear and apprehension, all of which affect the contractile characteristics
the Cardiology Division of the Medical Services, Lemuel Shattuck Hospital, Boston, Mass., and the Department of Medicine, Tufts University School of Medicine. investigation was supported by Grant NGR 22-012-006 from the National Aeronautics and Space Administration through the NASA Electronic Research Center. Cambridge, Mass. Received for publication Oct. 23, 1967. *Chief, Cardiology Division, Medical Services, Lemuel Shattuck Hospital; Assistant Professor of Medicine, Tufts ITniversity School of Medicine; Lecturer in Medicine. Boston TJniversity School of Medicine. **Assistant in Medicine, Tufts I‘niversity School of Medicine. Research Fellow, Cardiology, Lemuel Shattuck Hospital. This
498
American Heart Journal
Isovorumefric
of the myocardiunn. (2) Left ventricular movement appears to precede the onset of cavitary pressure rise (see below). Thus, depending on definition of IVCT, external detection of the very beginning of left ventricular contraction could be superior to catheter data. A variety of methods of atraumatically measuring I\,‘CT have been reported.l-7Ja-ifi We propose to compare these methods with the results of direct measurement and with each other and to suggest which may be the most reliable.
contraction
period of the
Material
and
left venfriclc
409
methods
A total of 50 normal active young men in a narrow age range (22 to 35 years) were studied. All had histories of total good health and had no physical, electrocardiographic, or roentgenological signs of heart or other disease. None was significantly obese and none was under any form of medication. 1Iultiple simultaneous cardiographic records were obtained on a Sanborn No. 56%100A eight-channel optical recorder at 75 mm. per second with the subject recumbent and in a relaxed expiratory apnea; these included : apexcardiogram (ACG) and phonocardiogram (with the use of the Sanborn No. 62-1500-Cl3 attachment and crystal microphone No. 374) and right external carotid arteriogram with the Sanborn No. TPS 10 pulse transducer. Calculations. IVCT was derived from these records by six different measurenlents1-7J-16(Fig. 1) : 1. The interval from the beginning of the ACG upstroke (ACGu) to that of the carotid (CAR) upstroke (CARu) : I\‘CT
= ACGu--CARu
(1)
2. i\Iethod Ko. 1 corrected for delay in pulse transmission time (PTT) of the central pulse to the carotid artery (see below) : IVCT
= ACGLI-(CARu
minus
PTT)
(2)
3. The interval between ACGu and the E-crest of the ACG: IVCT
= ACGu-E
(3)
4. The interval between the onset of the first rapid vibration of the first heart sound (“mitral sound”; In) and E: 4 5
IVCT
= 131-E
(1)
u PTT 2=!-#VT 6=5-
PTT
5. The interval between In ginning of the CARu: IVCT
Fig. 1. Indirect measurement of isovolumetric contraction period of the left ventricle; comparison of methods of calculation. Recordings, top to bottom: Electrocardiogram (ECG), carotid (CAR), apexcardiogram, apical phonocardiogram. Abbreviations: U, upstroke; In, incisure; E, E-point of ACG; rM, first rapid component of first heart sound; IIA, aortic component of second heart sound; PTT, pulse transmission time; I, 2, 3, 4, 5, 6, intervals used in calculations of isovolumetric contraction time (see text).
and be-
= I M-CARu
(5)
6. nIethod No. 5 corrected for PTT: IVCT
=
In-(CARu
minus
PTT)
(6)
PTT (“carotid delay time”) was measured by the interval between the aortic sound (11~) and the carotid incisura (CARI,) : PTT
= II*-CARr..
500
Table ment)
Spodick
rind h-zrmrrr
I. Isovolmvaetric
contmction
period
qf the
lqft ventricle
(comparison
of methods
of measure-
-___ 1 Kange Mean S.I). S.E.
(msec.)
70-120 94.1 13.9 2.1
I
2
I
JO-90 70.9 15.8
2.1
Results
Results of the various calculations are summarized in Table I. The mean values and ranges are rather disparate. JIethods 1 and 3 give means of 94.1 and 97.4 msec., respectively. Methods 4 and 5 yield means of 58.6 and 61.8 msec. Method 2 produces 70.9 msec. and method 6 39.0 msec. The narrowest ranges occur in methods 1 and 2, which also produce the least relative scatter (SD.). Discussion
The variability of results from different methods of measuring and computing IVCT, each based 011 formulas reported with confidence by some investigators,1-7z14-16 leads to an “embarrassment of choices,” which inevitably raises two questions: (1) How is the IVCT defined and does it require redefinition? (2) What criteria define a satisfactory indirect method of measurement? We shall attempt to answer these in reverse order and, in so doing, to arrive at a choice of the optimum method of determining IVCT. Dejinition of the II’CT. There is agreement that the end PO& of isovolumetric contraction is the onset of ejection. Since indirect recordings cannot be made from the ascending aorta, the time of onset of pressure rise (coincident with outward movement) of the carotid artery is used, with subtraction of the time for the pulse wave to travel from aorta to carotid-PTT. This delay appears to be the same at the onset as at the end of ejection7; indeed, it is precisely because of this relationship that left ventricular ejection
4
3 30-200 97.4 29.6 4.2
5
20-140 58.6 25.2 3.6
1
6 10-70 39.0 13.9 2.0
40-100 61.8 14.0 2.0
time is so reliably measured from carotid curves.8Fg Since the aortic sound (II*) is virtually coincident with aortic incisura, the PTT is the time between the appearance of 11~ and the carotid incisura (CARI,). For each subject, this interval can be deducted from the time of onset of the CARu to indicate the moment of ejection, and hence the endpoint of the IVCT. The exact beginning of isovolumetric contraction is not so easily establishedboth in physiological terms and in points of measurement. Thus, there are three potential isovolumetric contraction periods, each based on a different initial physiological event: 1.
THE
PERIOD
FROM
CLOSLTRE
OF
THE
This is the classic IVCT, measured internally by the time between crossing of the left ventricular pressure pulse curve first with the left atria1 curve and then with the aortic curve. Externally, this is approximated by the interval from I, to the ejection point. 2. THE PERIOD FROM THE BEGINNING OF MITRAL
VALVE
(‘.\VITARY
TO
EJECTION.
PRESSI!RE
RISE
To
EJECTION.
1%
this is measured from the onset of the left ventricular pressure curve (which precedes mitral closure) to its crossing of the aortic curve. Extevnully, this can be approximated by the interval from the initial ventricular deflection of the kinetocardiogram (KC(;) to the calculated ejection point. 3. THE PERIOD FROM THE EARLIEST DETEC‘Ttermlly,
ABLE
LEFT
VENTRICI‘LAR
MOVEMENT
TO
Internally, this cannot be measured. Extermlly, this is measured from the
EJECTION.
Isovolumetric
beginning of left ventricular motion to the calculated ejection point. The earliest detectable movement of left ventricular contraction (which precedes the rise of the pressure curve) is first registered by the ACGu; the initial ventricular deflection of the KCG occurs later. This relationship is reflected in the longer electromechanical lag of the KCG (mean = 38 msec.). Our shorter lag for the ACG of 22 nlsec.lo agrees with that of Levine’s group’ (21 tnsec. j. Reasons can be adduced for defining I\‘CT each way. It appears, however, that for purposes of external measurement, at the very least-and probably also in a physiological sense-it may be preferable to favor definition 3. The evidence for this may be summarized as follows: (1) left ventricular systole actually begins before the rise in left ventricular pressure; indeed, intramural pressure is well set up before cavitary pressure begins to rise,‘,“,” (2) this appears to be first detected by the ACG which usually rises before the pressure curve, and (3) the entire period of left ventricular contraction prior to ejection is encompassed. (Fortuitously, the necessarily longer period thus defined reduces the error inherent in measuring smaller intervals.) We shall return to these considerations later. With the foregoing in mind, it is necessar!. to define satisfactory indirect measurement before discussing our specific results. To be acceptable, any indirect method must fulfill three postulates: Postulates indirect
for acceptability of methods of measurement
I Results must duplicate or reasonably approximate those of any comparable direct method. II Calculations should be based on measurements reflecting the actual physiological events involved, i.e., if the numerical results are comparable with those of direct methods, this should not be accidental. III If more than one calculation fulfills Postulates I and II, the optimum method will be that for which the points measured can be established with greatest confidence in the technique of recording and identification. In view of these criteria, there are spe-
contmction
period of the left ventricle
50 1
cific objections to certain points used in various formulas for external derivation of IVCT. With regard to the endpoint of IVCT, the E-crest of the ACG is unsatisfactory, primarily because it does not appear to represent the actual onset of ejection2sy; indeed, its timing has a fair, though rather variable, correlation with the onset of the CARu-which must occur after the beginning of ejection. Indeed, left ventricular ejection times calculated from the E-crest to 11~ do not correlate satisfactorily with more accurate methods of measuring ejection time.“~8~gFinally, E often is a fairly broad summit and therefore susceptible to much more error of measurement than the relatively clear points at which the apex and carotid upstrokes depart. With regard to the heginning of IVCT, if this interval is defined as commencing with either the initial left ventricular movement (ACGu) or with the beginning of left ventricular pressure rise, it is clear that Ihf occurs much too late. Furthermore, even in terms of the classic IVCT beginning with mitral closure, I ~if remains a late event; it occurs after the crossing of the left ventricular and left atria1 pressure curves by as much as 40 nisec.,13 i.e., when the mitral valve is already closed and when there is already a relatively large V-A pressure gradient.13J4 Our results with each method of external measurement (Table I) may now be examined in the light of the foregoing discussion and in terms of the three postulates delineating satisfactory external measurements. Calcddion 5. IVCT = IbI-CARu = 61.8 f 14.0 msec. This result is extremely close to that of Braunwald and colleagues15 (61 f 12.1 msec.), for an IVCT beginning with the onset of left ventricular pressure rise (Definition 2 above). However, Postulate II obviously is not fulfilled since the result is accidental; the remarkable resemblance can be ascribed to a purely fortuitous cancellation of the delay in appearance of IM by that of CARu. Cdcdation 6. IVCT = IJI--(CARu PTT) = 39.0 =I= 13.9 msec. This should represent the classic IVCT noted in I>efinition 1; it agrees well with the 38 msec. mean of Holldack,“a which is based on essentially the same calculation. hIore-
502
Spodick and Kumar
over, if the mean of Tafur and associates’ for the same measurement (“PEC II”) is reduced by our mean PTT of 26 msec., a similar figure also results (41 msec.). Yet, other investigators report rather disparate mean values (Frank and Kinlaw6 49 msec., Raineri4 30 msec., and Merlen” 32.5 msec.). The discrepancy of approximately f 10 msec. probably represents variability in recording and measuring I&l--the first rapid vibration of the first heart sound; this means that Postulate III is difficult to fulfill for technical reasons. Even more important, Postulate II cannot be fulfilled since, as already noted, 101 is at best a late phenomenon. Indeed, on these grounds, it is difficult to understand the high figure reported only by Frank and Kinlaw. CaZcuZrAon 4. IVCT = Ill-E = 58.6 & 25.2 msec. This yields a result reasonably close to that of Calculation 5, probably because of the general correspondence of the timing of E to that of CARu noted by us9and others.2 It cannot be accepted, both because of the objections already cited for use of 101 and because E does not appear to represent true ejection (Postulate II not fulfilled). CaZczLZation3. IVCT = AC(;u-E = 97.4 f 29.6 msec. This result must also be rejected because of the objections cited for using E. Calculation 1. IVCT = ACGu-CARu = 94.1 =t 13.9 msec. This figure is quite close to that of Tafur and associates’ for the same measurement (102 msec.), but does not allow for PTT. Significantly, its mean of 94.1 msec. is very close to the 97.4 msec. of Calculation 3. This reflects the rough correspondence of E and CARu; the greater scatter in Calculation 3 (SD. twice that of Calculation 1) reflects the great variability of the E crest. Calculation 2. IVCT = ACGu-(CARu - PTT) = 70.9 + 15.8 msec. This result agrees well with that of Oreshkove2 for the same measurement (67 msec.). RIoreover, if our mean PTT of 26 msec. is subtracted from the result of Tafur and associates’ for Calculation 1 (above) this will yield 76 msec., which also approximates our result. The IVCT of Harrison and co-workers,7 measured from the “initial ventricular movement” of the kineto-
cardiogram to CARu - PTT, gave a mean value of about 63 msec. for men in the age group studied by us; since the end points are identical, the difference can be ascribed to the shorter electromechanical lag of the ACG as compared to the KCG. Calculation 2 appears to he the optimum method for measuring 11’CT based on the inclusive definition of this period. Indeed, Wiggers17 considered the period of rising left ventricular pressure in advance of mitral closure “so nearly isometric” as to warrant inclusion in the IVCT. By the same reasoning, the earliest contractile movement of the left ventricle, probably the result of the earliest intramural tension, is no less isometric and, therefore, cannot be ignored. Indeed, this relationship is clearly indicated in recent studies” which demonstrate a relatively steep increment in intramural left ventricular pressure well before cavitary pressure begins to rise. Conclusions
1. The IVCT is best defined as the total systolic period before ejection, at least for purposes of external measurement and probably also in a physiological sense. Specifically, it commences with the earliest left ventricular movement which appears to result from rising intramural tension in advance of the cavitary pressure rise. 2. The ACG records left ventricular motion before other external or internal methods; thus IVCT is best measured from the onset of its upstroke (ACGu) to the calculated ejection point. For external measurement, beginning ejection is calculated from the onset of the carotid pulse minus the time taken for pulse transmission from the ascending aorta. Our result for IVCT, therefore, is expressed as follows: IVCT = ACGu-(CARu
- PTT)
= 7F.9 * 15.8 msec.
3. Other methods of calculation appear to give widely divergent values for IVCT based both on the definition of IVCT used (and hence the points measured) and on the variability among investigators for results of the same methods. This variability appears to be due to the use of points of measurement which ma)
l’olnme
Sumber
76
Isovolumetric
4
not coincide with actual physiological events or which lack precise definition in recording. (An exception to this is the use by Harrison and co-workers’ of the “initial ventricular movement” of the IiCG which appears to approximate the beginning of left ventricular cavitary pressure. IVCT measured from this point to the calculated ejection point reflects a period which is susceptible to internal measurement; but it is shorter than that using the ACG, owing to the greater electromechanical lag of the IiCG and does not include the period of rising mural pressure.)
contraction
4.
5.
6.
7.
8.
Summury The isovolumetric contraction period of the left ventricle (IVCT) was measured atraumatically by six different cardiographic methods in 50 normal young men. IVCT has been redefined as the total period of left ventricular contraction prior to ejection-i.e., the period of left ventricular mural tension + the period of rising cavitary pressure. The ACG detects the earliest inception of left ventricular systole; both for accuracy of indirect measurement and physiologically the onset of its upstroke appears to be the beginning of isometric contraction. Our results for this period are 70.9 =t 15.8 msec., with the ejection point calculated by deduction of the PTT from the carotid upstroke. The results of other methods of calculation and other points of measurement are compared and discussed.
9. 10. 11.
12.
13.
14.
15.
REFERENCES 1. Tafur, The
E.,
Cohen,
L. S., and
Levine,
H.
D.:
normal apexcardiogram. Its temporal relationship to electrical, &oustic and mechanical cardiac events. Circulation 30:381. 1964. 2. Oreshkove, V.: Indirect measurement of isovolumetric contraction time on the basis of polygraphic tracing, Cardiologia 47:315, 1965. 2a. Holldack. K.: Cited bv Oreshkove? 3.
Benchimol,
A., and Dimond,
E. G.: The
normal
16.
17.
period of the left ventricle
503
and abnormal apexcardiogram. Its physiologic variation and its relation to intracardiac events, Am. J. Cardiol. 12:368, 1963. Raineri, A.: I1 cardiogramma apicale nella valutazione della dinamica cardiaca, Boll. Sot. Ital. Cardiol. 10:64, 1965. Merlen, J. F.: La phase isometrique de la systole ventriculaire, Actual. cardioangeiol. int. 14:119, 196.5. Frank, M. N., and Kinlaw, W. B.: Indirect contraction measurement of isovolumetric time and tension period in normal subjects, Am. J. Cardiol. 10:800, 1962. Harrison, T. R., Dixon, Ii., Russell, R. O., Jr., Bidwai. P. S.. and Coleman. H. N.: The relationship of age to the duration of contraction, ejection, and relaxation of the normal human heart, AM. HEART J. 67:189, 1964. Weissler, A. M., Peeler, R. G., and Roehll, \V. H.. lr.: Relationshios between left ventricular ejection time, stroke volume, and heart rate in normal individuals and patients with cardiovascular disease, A&f. HEART J. 62:367, 1961. Spodick, D. H., and Kumar, S.: Left ventricular ejection period, AM. HEART J. (in press). Spodick, D. H., and Kumar, S.: Electromechanical lag of the left ventricle. In preparation. Dieudonne, J. M.: Tissue-cavitary difference pressure of dog left ventricle, Am. J. Physiol. 213:101, 1967. Rios, J. C., and Massumi, R. A.: Correlation between the apex cardiogram and left ventricular pressure, Am. J. Cardiol. 15:647, 1965. DiBartolo, G., Nunez-Dey, D., Muiesan, G., MacCanon. D. M.. and Luisada. A. A.: Hemodynamic cdrrelates’of the first heart sound, -4m. J. Physiol. 201:888, 1961. Luisada, A. A., and Alimurung, N. M.: An encyclopedia of the cardiovascular system, in Luisada, A. A., editor: Cardiology, Vol. 1, New York, 1959, McGraw Hill Book Co., Inc., pp. 2-92. Braunwald, E., Fishman, A. P., and Cournand, A.: Time relationships of dynamic events in the cardiac chambers, pulmonary artery and aorta in man, Circulation Res. 4:100, 1956. Holldack, K.: Atlas und kurzgefasstes Lehrbuch der Phonokardiographie, Stuttgart, 1956, Thieme Verlag, p. 39. \&‘iggers, C. J.: Studies on the consecutive phases of the cardiac cycle. I. The duration of the consecutive phases of the cardiac cycle and the criteria for their precise determination, t\m. J. Physiol. 56:415, 1921.