- Email: [email protected]
Left ventricular hemodynamics in mitral stenosis
Left Ventricular
Hemodynamics
Mitral
Stenosis* M.D., F.A.C.C. and ALDO
.J. SLODKI,
Chicago,
T
HE
relation
dynamic
traction been
of either thr
other
delayed
first
munerous
changes,
the loud,
has been
soruld
variously
ond sound also has been studies.
The
present
taken in an effort phenomrlla
in patients
regard
second
heart so~~t~ls.
of
explained. the object
investigation with
ulitral
and
this
con-
The
sec-
of numerous was
different
to the alterations
con-
stenosis has
snapping
under-
IJ..~.(:.c.
Statham strain gauges were used for both right and left heart catheterization, this delay is of no con‘l‘he peak resonance of the cathctersequence. strain gauge system. determined in our laboratory, is at 35 c.p.s. ‘I’he rate of change (dp/dt) of left ventricular pressure (first derivative) \vas obtained by linear differentiation of the pressure curve to 50 c.p.s. with an RC analog computer. During the procedure? an external phonocardiogram was recorded in most cases with a Sanborn contact microphone. Phonoccudiogmms: Intracardiac phonocardiograms \vere also obtained by using a previously described method’* [lluid column transmission (FCI‘) system]. Again, the Dallons-Telco catheter tip MSD8 was used in comparison \vith an FCT microphone, mormtcd to the side arm of a Statham strain gauge, to lvhich a No. 7 Cournand catheter \vas attached; the tips of both catheters \vcre introduced into a \I-ater-filled balloon, which was tapped to generate a signal: fed through the FC’I’ microphone to a Sanborn sound preamplifier ‘l’he delay of the sound signal recorded No. 1700B.
dynamic
stenosis with
of the first and
Scventern patients with mitral stenosis were studied The in the Heart Station of Mount Sinai Hospital. work-up included a complete medical history and physical examination, blood count, sedimentation electrocardiogram, phonorate. serology. urinalysis, simultaneous right and left cardiac cardiogram, This group catheterization, and angiocardiogram. of patients included 10 \vith pure mitral stenosis, 4 with mitral stenosis combined lqith aortic insufand ficiency, 2 lvith mitral stenosis and insufficiency, 1 with mitral stenosis combined with aortic stenosis. Crhetrrization: A catheter introduced into a right antcc,llbital vein was advanced to the right side of the heart while the left side was reached by percutaneous puncture of the right femoral artery by Seldinger’s technic. The pressure transducers jvere Statham strain gauges P23D and the recording \vas done on a Sanborn multichannel photographic recorder (Model 550M). The paper speed was 200 mm./scc. No. 7 or 8 Cournand catheters were used for right heart catheterization, and a ‘Teflon’” spring guide catheter No. 7 for the left heart. Both were 135 mm. long. The left ventricle was entered through the aortic The catheters mounted valve in a retrograde fashion. to the Statham strain gauges were compared with a * From the Division of (Medicine), Mount Sinai Training Grants HE-5002 tute, Cl. S. Public Health
xn.,
Dallons-‘l‘elco (MSD8 tip) system. which has no delay. The tips of the Cournand and the DallonsTelco catheters were introduced into a Icater filled balloon. and the Statham strain gauge was connected The to a Sanborn carrier preamplifier (350-170OB). systems lvere activated by tapping the balloon. These tracings sho\v that the delay of the Cournand catheter-Statham strain gauge system, as compared to Since the Dallons-‘Delco, is about 5 milliseconds.
to the
the
A. LUISADA,
Illinois
speculations.
typical
to correlate
special
by
in mitral
of
heart
sound
heart caused
ventricle
object
Among dition
of the first phenolnena
in
by the FC’I’ microphone is the same as that of the The FC’T microphone has pressure signal (5 msrc.). -l‘hc srnsitivity a resonant peak of about 260 c.p.s. drops off rapidly above 400 c.13.s.. but an excellent response is observed up to that frequent!.. Tracings: Simultaneously recorded pressure tracings from the left ventricle and a branch of the pul* This was an external sonar microphone. I‘he sound signals are transmitted from the heart to the microphone through the fluid column of the catheter IFCT system).
Cardiovascular Research, The Chicago Medical School, and the Division of Cardiology This study was conducted during trnure of Hospital and ‘l‘he Chicago Medical School. and HE-5182 and with the aid of Research Grant HE-09350 of the National IHcart InstiService.
VOLUMI’. 19, FEBRUARY 1967
183
184
Kurz,
Slodki
Summary Case
NO.
and
Luisada
TABLE I of Data Obtained RRP. LV
RRP. RV
39 36 35 26 36 35 38 36 39 38
2,450 2,125 1,680 1,750 2,189 1,800 2,416 2,350 1,900 2,100
1,203 1,076 860 1,120 1,500 1,200 805 1,325 948 1,184
22 21 46 18 42 48 21
1,840 2,611 2,230 2,000
1,430 1,318 1,308 1,200
2;150 1,837
1;350 1,336
@IA
QpLV
Q-RV
Q-r
P’.
Q-IIA
CO
GI
SV
2,940 2,400 2,300 1,700 2,430 2,020 2,100 2,400 2,150 2,300
60 61 67 49 60 49 55 61 60 63
2,100 2,000 4,400 1,800 2,570 2,200 2,200
45 38 74 31 65 75 35
SI
A. Patients with Pure Mitral Stenosis 1 2 3 4 5 6 7 8 9 10
0.040 0.039 0.050 0.060 0.045 0.050 0.045 0.055 0.060 0.055
-_
0.060 0.060 0.095 0.100 0.049 0.070 0.080 0.065 0.068 0.063
0.058 0.060 0.090 0.090 0.060 0.090 0.070 0.080 0.085 0.079
_
0.354 0.387 0.398 0.387 0.365 0.394 0.387 0.361 0.370 0.375
0.380 0.380 0.380 0.420 0.360 0.380 0.378 0.392 0.365 0.370
4,880 4,000 3,800 3,170 3,950 3,080 3,450 4,000 3,700 4,100
B. Patients with Combined Lesions 11 12 13 14 15 16 17
0.060 0.080 0.060 0.060 0.060 0.070 0.055
0.080 0.140 0.080 0.090 0.095 0.080 0.045
0.080 0.120 0.080 0.090 0.085 0.110 0.080
0.393 0.334 0.348 0.311 0.411 0.411 0.394
0.378 0.360 0.352 0.340 0.390 0.390 0.400
3,100 3,400 7,100 3,080 3,930 4,600 3,500
Q-LV = Onset of Q wave to onset of left ventricular pressure in seconds; Q-RV = onset of Q wave to onset of right ventricular pressure in seconds; Q-IIA pr. = predicted Q-IIA interval according to rate in seconds; Q-IIA = Q-IIA interval found in seconds; CO = cardiac output in ml./min.; CI: cardiac index in ml./min./M.2; SV = stroke volume in ml.; SI = stroke index in ml/M.‘; RRP LV = rate of rise of pressure in the left ventricle in mm. Hg/sec. ; and RRP RV = rate of rise in the right ventricle. monary artery (wedge pressure) were recorded for Pressure traccalculation of the mitral valve area. ings from the ascending aorta, main pulmonary and right atrium were also artery, right ventricle Intracardiac phonocardiograms were obrecorded. tained in most patients from all chambers and vessels simultaneously with their respective pressure tracings, The in addition to the external phonocardiograms. sound tracings were recorded with a high pass filter having a nominal frequency of 100 c.p.s. and a slope of 24 db/octave. An electrocardiogram was recorded with all other tracings, usually lead II. However, one of the other standard leads was occasionally used for better definition of the QRS complex. Measurements: Pressures were determined in all the chambers entered. The mitral valve area was calculated using Gorlin’s formula in all cases of pure mitral stenosis and in most cases of mitral stenosis associated with aortic stenosis or insufficiency. The cardiac output was determined by the direct Fick method. Special Measurements: The following measurements were made: (1) time between the onset of the electrocardiographic Q wave to the onset of left ventricular and of right ventricular pressure pulses; (2) time between the onset of the Q wave and the onset of systolic rise of the first derivative of each ventricle;
(3) Q-I interval (interval between onset of the and the onset of the first rapid vibration of heart sound) ; (4) Q-IIA interval (onset of Q onset of the aortic component of the second
Q wave the first wave to sound).
The formula Q-IIA = 61.6 + 10.24 dR-R established by Shah and Slodki2 was used to determine the predicted Q-IIA interval for the heart rate of the patient*; (5) interval between the onsets of the right and left ventricular pressure pulses; (6) the maximal rate of rise of pressure in mm. Hgjsec. in each ventricle; and (7) the stroke volume and the stroke index. Statistical analysis was made of the data obtained.
RESULTS I n patients . interval the
between
onset
ranged 0.049
with
of the from
f
the left
0.039
0.002t)
pure
mitral
onset
of the
ventricular to
the and
pressure
0.060
(normal
stenosis, Cj wave
second interval
pulse (mean
averages
* Since it was impossible to eliminate AC interference from the electrocardiogram in several cases, the true duration of the QRS complex was determined in the routine electrocardiogram, taken prior to cardiac catheterization. t Standard error. THE
AMERICAN
JOURNAL
OF
CARDIOLOGY
Hemodynamics
in Mitral
185
Stenosis
FK. 1. Z’atimt with pure mitral stmosi~, in whom the first sound iI-abr) has its onset before the onset of the right ventricular contraction. Silnultaneous pressures of right and left ventricles, exphonocnrdiogram (ext ternal PCG I, left ventricular phonocardiogram [IC (FCT) LV], right ventricular phonocardiogram [IC IFCT) RV], the first derivative of the left ventricle (1st D.LV) and electrocardiogram, lead 11 (ECG) are seen. AC artifacts are visible in the electrocardiogram and first derivative tracing. Left ventricular phonocardiogram shows the first (I), srcond (II) and fourth (IV) heart sounds, the opening snap (OS) and a presystolic murmur (PM). In the right ventricular phonocardiogram these phenomena are very faint or nonexistent. (Recording speed = 50 I~~IlL/SfX.,
abc
)
-r
0.039).3 The interval from the onset of Q to the onset of the right Lrentricular pressure pulse was between 0.049 and 0.100 second (mean 0.07 * 0.004) (normal interval averages 0.045).3 In patients with combined lesions, these intervals were longer, being from 0.055 to 0.080 second (mean 0.063 f 0.005) for the left ventricle and from 0.045 to 0.140 second (mean 0.081 f 0.009) for the right ventricle (Table IB). The mean difference of 0.056 f 0.005 for the left ventricle and of 0.075 * 0.009 for the right ventricle is statistically significant (lo < 0.05 and p < 0.02, respectively).* The onset of the first systolic wave of the first derivatives of left and right ventricular pressures was simultaneous with the onset of the respective pressure curve. The Q-Z interval was prolonged in all the cases studied, 0.04 to 0.12 second (mean 0.080 * in comparison with normal averages 0.004), The patients with combined lesions of 0.05.4 showed a higher average (mean 0.088 =t 0.006) than those with pure mitral stenosis (Table IB). These differences are statistically significant (t = 2.25, p < 0.05). In all cases studied, the rise of pressure in the left ventricle preceded * t test done comparing stenosis and that with with other lesions. VOLUME
19,
FEBRUARY
the group with pure mitral mitral stenosis in combination
1967
that of the right as it does in a nortnal heart.f The time difference between the two rises of pressure was 0.010 to 0.045 second (average 0.023 sec.) (Table I). The relation between Q-I and the onset of right ventricular pressure rise was variable (Table I). Only in some cases did the onset of the first sound coincide with the rise of right ventricular pressure (Case 2, pure mitral stenosis, (Table IA, and Cases 11, 13 and 14, combined defects, Table IB); in others, the onset of the first sound preceded the rise of right ventricular pressure (Cases 1, 3, 4, 7, 12 and 15, Table I)* In the remainder of the cases, the first sound occurred after the rise of right ventricular pressure. Figure 1 shows that the onset of the first sound precedes slightly the onset of the right ventricular pressure curve; the first component of the first sound (Ia) occurs before the onset of right ventricular pressure; the second and third components (It) and IC) occur early at the upstroke of the right ventricular pressure curve when the tricuspid valve is already closed. The Q-ZZA interval in patients with pure mitral stenosis was decreased ; in general, the Q-HA t This fact was observed even in a case of extremely severe mitral stenosis with right ventricular pressure at the level of systemic pressure (RV = 91/6-18) which was studied while this paper was being completed.
186
Kurz,
Slodki
and
Luisada
FIG. 2. Puttentwith mitral stenosis. The first derivative of the left ventricular pressure (1st D.LV) shows a phase of very slow rate of change (a-a) at the onset of ventricular systole, followed by a phase of very rapid rise. 1\C artifacts are visible in the electrocardiogram and first derivative tracing. (Recording speed = 200 mm./sec.)
interval in the group of patients with pure mitral stenosis (Table IA) was shorter than the predicted Q-IIA interval for that particular heart rate in 7 cases, and was larger in the remaining 3 patients of this group (Cases 1, 4 and 8, Table IA) ; however, these 3 patients had systemic hypertension, a fact that may account for the finding. In the patients who had mitral stenosis combined with another lesion, again the Q-IIA interval was decreased in the normotensive and increased in the hypertensive patients (Cases 12, 13, 14 and 17). The rate of rise of pressure in the patients with pure mitral stenosis was from 1,680 to 2,450 mm. Hg/sec. (average 2,092) in the left ventricle (normal 841 to 1,696, average 1,219 mm. Hg/sec.),5 and from 805 to 1,500 mm. Hg/sec. (average 1,134) in the right ventricle (normal 223 to 296, average 258 mm. Hg/sec.).5 In the group with combined lesions, the rate of rise of pressure was from 1,250 to 2,611 mm. Hg/sec. (average 2,039) in the left ventricle, and from 1,200 to 1,675 mm. Hg/sec. (average 1,373) in the right ventricle (Table IB). Therefore, there was not much difference between the two groups, both of which had mitral stenosis. Plotting of the Q-I interval against the stroke volume and stroke index in patients with pure mitral
stenosis suggests that a decrease in stroke volume is accompanied by an increase in the Q-I interval (r = -0.65 f 0.06). The Q-IIA interval in this group of patients, when plotted against the same parameters, shows a tendency to decrease except when arterial hypertension is present, in which case the Q-IIA interval increases. The behavior of the Q-I and Q-IIA intervals in the group of patients with combined lesions or aortic stenosis is similar to that of the patients with pure mitral stenosis (r = -0.89 f 0.07). If we compare our clinical data with those of Di Bartolo et a1.3 (in normal dogs), it is apparent that the intervals between the onset of the Q waves and the onset of the ventricular pressure rises lie in the upper limits of normal. Since in man the normal Q-I interval is slightly longer than in large dogs, our figures may still be within normal limits. The rate of rise of pressure in all our cases was significantly increased in both ventricles. In cases of pure mitral stenosis, two phases in the curve of the first derivative were observed: (1) a slow phase, which occurred while the mitral valve was still open; and (2) an extremely rapid phase after mitral valve closure (Fig. 1, 2). The first group of vibrations of the first sound THE
AMERICAN
JOCJRNAL
OF
CARDIOLOGY
Hemodynamics coincided kvith the rapid rise of the systolic wave of the first derivative and followed the early slow phase which does not exist in normal subjects.
The relation of the various phenomena that have their expression in the sounds and pressure changes detected by clinical and laboratory methods have been studied by various investigators. Frank,6 Wiggers’ and Starling and VisscherK emphasized the importance of the rate of change of pressure as an important and fundamental property of the heart muscle. Reeves et a1.,g and Gleason and Braunwald5 studied rate of change (first derivative or dp/dt) of the left ventricular pressure, and demonstrated that it has a direct relation to myocardial contractility and to the maximal tension potential of the ventricle at the onset of contraction. The relation of the heart sounds and their different components to the other phenomena was studied by Di Bartolo et a1.,3 Shah et al.,‘0 Sakarnoto et al.,ll and Mori et a1.,12 all in this laboratory. It was ascertained that the first group of vibrations of the first heart sound coincides with the rise of the early-systolic wave of the first derivative of left ventricular pressure and precedes its peak. This is true in both experilnental animals and man. Di Bartolo et a1.3 demonstrated in dogs that the normal first heart sound is recorded at a time when the atrioventricular valves are already closed, and that the production of this sound has no causal relation with the closure of the valves. The same was also found true in man without valvular lesions by observing the clinical tracings recorded in our laboratory (some of the patients had flow murmurs and no lesions of the valves). Apparently, the rise of pressure of the left ventricle is responsible for accelerations and decelerations of blood that cause a vibration of the entire system of valve leaflets, chordae, septum, free cardiac walls, blood and vessels and, hence, for the production of the first sound. These findings were confirmed by van Bogaert et a1.13 and by Piemme et a1.14 Since there is no abnormal delay between onset of the electrical activity of the ventricle (Q wave) and onset of the mechanical activity (onset of pressure rise), the delay of the first sound in mitral stenosis might seem connected with the delay in mitral valve closure, because the valve will not close until left ventricular pressure has reached and surpassed the level VOLUME
19,
FEBRUARY
1967
in Mitral
Stenosis
187
of left atria1 pressure. However, further considerations will be presented later which will modify this statement. After a slow beginning, the rate of rise of pressure in the left ventricle is increased in cases of pure mitral stenosis (Fig. 1, 2) ; in this lesion the mitral leaflets and the mitral ring are more rigid than in normal subjects. This rigidity decreases the bulging of the valve leaflets into the left atrium which normally occurs during- isovolumic contraction,15 and tends to increase the rate of rise of pressure and therefore the loudness of the first heart sound. The pattern of the first derivative of left ventricular pressure was found significantly altered in mitral stenosis (Fig. 2). It showed at first a slow rise during the first part of isovolumic contraction (a-a)? revealing that the left ventricular tension could not rapidly increase until the level of left atria1 pressure had been reached; thereafter, a very rapid rise occurred. Jll mitral stenosis, the entire left ventricular onusculature is already contracting at the time of mitral valve closure, as evidenced by the normal interval between Q and onset of left ventricular pressure and the prolonged Q-I; this sequence should be compared with the normal sequence of events because, in the normal heart, the mitral valve closes first, and then the left ventricular fibers gradually start to contract.“’ In mitral stenosis, the left ventricle starts contracting while the mitral valve is still open. This sequence of events, which causes an initial slow rise of left ventricular pressure (revealed by the initial portion of the first derivative), seems to be an additional factor for the late but extremely rapid rise of pressure and for the loud and delayed first heart sound. The increase in the rate of pressure rise in the right ventricle may be explained by the right ventricular hypertrophy typical of mitral stenosis. As pointed out before, the relation between the first heart sound and the right ventriculqr pressure curve was variable in our studv. The first component of the first heart sound ‘in some of our cases occurred before the onset of the right ventricular curve; the second and third components of the first heart sound occurred at a time when the tricuspid valve was already closed. These facts suggest that, as we previously demonstrated in the normal heart, the right ventricle does not contribute appreciably to the first heart sound, even in cases of mitral stenosis. This view is in contrast with that of Leo and Hultgren,‘7 who thought
Kurz,
188
Slodki and Luisada
that a “tricuspid” component preceded a “mltral” component of the first sound in cases of mitral stenosis. The unimportant contribution of the right ventricle is further substantiated b) the fact that the first sound is well recorded in the left ventricular cavity and only barely demonstrable in the right ventricular phonoIt is further confirmed by recent cardiogram. experiments of this laboratory with right heart bypass,18 demonstrating a persistence of the various components of the first heart sound. %JMMARY
Seventeen patients with mitral stenosis were studied by right and left cardiac catheterization. intracardiac phonocardioPressure tracings, grams, cardiac outputs and valve areas were determined ; several measurements were made. The data indicate that: (1) the first sound is delayed ; (2) following an initial slow rise, the rate of rise of pressure of the left ventricle is sharply increased ; and (3) the rate of rise is The inincreased in the right ventricle also. crease of the maximal rate of rise of ventricular pressure in pure mitral stenosis is explained by the lack of early systolic bulging of the mitral leaflets into the left atrium and by the fact that closure of the mitral valve occurs during left ventricular contraction, not before it, as in norOn the basis of simultaneous inmal subjects. tracardiac phonocardiograms in the left and right ventricles, it is suggested that the right ventricle contributes little to the first heart sound, as recorded from the surface of the chest, even in cases with mitral stenosis. It is further shown that a decrease in stroke volume will increase the duration of the Q-I interval and decrease the duration of the Q-HA
3.
4.
5.
6. 7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
interval. REFERENCES 1. LIJISADA, A. A., MACCANON, D. M. and SLODKI, S. J. Intracardiac phonocardiography. Description of a new simplified system. Circulation, 32: 563, 1965. 2. SHAH, P. M. and SLODKI, S. J. The Q-II interval: .4 study of the second heart sound in normal
17.
18.
adults and in systemic hypertension. Circulation, 29: 551, 1964. Dr BARTOLO, G., NUNEZ-DEY, D., MUIESAN, G., MACCANON, D. M. and LUISADA, A. A. Hemodynamic correlates of the first heart sound. Am. J. Physiol., 201: 888, 1961. SAKAMOTO,T., KAITO, G. and UEDA, 1~. Electrocardiographic and phonocardiographic studies in hypertension. II. Phonocardiographic study with special reference to the atria1 sound and “Q-I” interval. Ja#. Heart J., 1: 213, 1960. GLEASON, W. L. and BRAUNWALD, E. Studies on the first derivative of the ventricular pressure pulse in man. J. Clin. Invest., 41: 80, 1962. FRANK, 0. Zur Dynamik des Herzmuskels. Ztschr. B&l., 32: 370, 1895. WIGGERS, C. 3. Some factors controlling the shape of the pressure curve in the right ventricle. Am. J. Physiol., 33: 382, 1914. STARLING, E. H. and VISSCHER,M. B. The regulation of the energy output of the heart. J. Physiol., 62: 243, 1927. REEVES, T. J. et al. The hemodynamic determinants of the rate of change in pressure in the left ventricle during isometric contraction. Am. Heart J., 60: 745, 1960. SHAH, P. M., MORI, M., MACCANON, D. M. and LUISADA, A. A. Hemodynamic correlates of the various components of the first heart sound. Circulation Res., 12: 386, 1963. SAKAMOTO,T., KUSUKAWA, R., MACCANON, D. M. and LUISADA, A. A. Hemodynamic determinants of the amplitude of the first heart sound. Circulation Res., 16: 45, 1965. MORI, M., SHAH, P. M., MACCANON, D. M. and LUISADA, A. A. Hemodynamic correlates of the various components of the second heart sound. Cardiologia, 44: 65, 1964. VAN BOGAERT, A. et al. Contribution 1 1’ Ctude du premier bruit du coeur normal. Arch. mal. coeur, 55: 368, 1962. PIEMME, T. E., BARNETT, G. 0. and DEXTER, L. Relationship of heart sounds to acceleration of blood flow. Circulation Res., 18: 303, 1966. CHAILLET, J. L. Cineradiography of Cardiac Valves Utrecht, 1965. Drukkerij J. & D. van in Man. der Horst. SARNOFF, S. J. and MITCHELL, J. H. The regulation of the performance of the heart. Am. J. Med., 30: 747, 1961. LEO, T. and HULTGREN, H. Phonocardiographic characteristics of tight mitral stenosis. Medicine, 38: 85, 1959. LUISADA, A. A., KURZ, H., SLODKI, S. J. and MACCANON, D. M. Normal iirst heart sounds with nonfunctional tricuspid valve or right ventricle. Ciwulation, in press.
THE AMERICANJOURNAL OF CARDIOLOGY
Hemodynamics
Mitral
Stenosis* M.D., F.A.C.C. and ALDO
.J. SLODKI,
Chicago,
T
HE
relation
dynamic
traction been
of either thr
other
delayed
first
munerous
changes,
the loud,
has been
soruld
variously
ond sound also has been studies.
The
present
taken in an effort phenomrlla
in patients
regard
second
heart so~~t~ls.
of
explained. the object
investigation with
ulitral
and
this
con-
The
sec-
of numerous was
different
to the alterations
con-
stenosis has
snapping
under-
IJ..~.(:.c.
Statham strain gauges were used for both right and left heart catheterization, this delay is of no con‘l‘he peak resonance of the cathctersequence. strain gauge system. determined in our laboratory, is at 35 c.p.s. ‘I’he rate of change (dp/dt) of left ventricular pressure (first derivative) \vas obtained by linear differentiation of the pressure curve to 50 c.p.s. with an RC analog computer. During the procedure? an external phonocardiogram was recorded in most cases with a Sanborn contact microphone. Phonoccudiogmms: Intracardiac phonocardiograms \vere also obtained by using a previously described method’* [lluid column transmission (FCI‘) system]. Again, the Dallons-Telco catheter tip MSD8 was used in comparison \vith an FCT microphone, mormtcd to the side arm of a Statham strain gauge, to lvhich a No. 7 Cournand catheter \vas attached; the tips of both catheters \vcre introduced into a \I-ater-filled balloon, which was tapped to generate a signal: fed through the FC’I’ microphone to a Sanborn sound preamplifier ‘l’he delay of the sound signal recorded No. 1700B.
dynamic
stenosis with
of the first and
Scventern patients with mitral stenosis were studied The in the Heart Station of Mount Sinai Hospital. work-up included a complete medical history and physical examination, blood count, sedimentation electrocardiogram, phonorate. serology. urinalysis, simultaneous right and left cardiac cardiogram, This group catheterization, and angiocardiogram. of patients included 10 \vith pure mitral stenosis, 4 with mitral stenosis combined lqith aortic insufand ficiency, 2 lvith mitral stenosis and insufficiency, 1 with mitral stenosis combined with aortic stenosis. Crhetrrization: A catheter introduced into a right antcc,llbital vein was advanced to the right side of the heart while the left side was reached by percutaneous puncture of the right femoral artery by Seldinger’s technic. The pressure transducers jvere Statham strain gauges P23D and the recording \vas done on a Sanborn multichannel photographic recorder (Model 550M). The paper speed was 200 mm./scc. No. 7 or 8 Cournand catheters were used for right heart catheterization, and a ‘Teflon’” spring guide catheter No. 7 for the left heart. Both were 135 mm. long. The left ventricle was entered through the aortic The catheters mounted valve in a retrograde fashion. to the Statham strain gauges were compared with a * From the Division of (Medicine), Mount Sinai Training Grants HE-5002 tute, Cl. S. Public Health
xn.,
Dallons-‘l‘elco (MSD8 tip) system. which has no delay. The tips of the Cournand and the DallonsTelco catheters were introduced into a Icater filled balloon. and the Statham strain gauge was connected The to a Sanborn carrier preamplifier (350-170OB). systems lvere activated by tapping the balloon. These tracings sho\v that the delay of the Cournand catheter-Statham strain gauge system, as compared to Since the Dallons-‘Delco, is about 5 milliseconds.
to the
the
A. LUISADA,
Illinois
speculations.
typical
to correlate
special
by
in mitral
of
heart
sound
heart caused
ventricle
object
Among dition
of the first phenolnena
in
by the FC’I’ microphone is the same as that of the The FC’T microphone has pressure signal (5 msrc.). -l‘hc srnsitivity a resonant peak of about 260 c.p.s. drops off rapidly above 400 c.13.s.. but an excellent response is observed up to that frequent!.. Tracings: Simultaneously recorded pressure tracings from the left ventricle and a branch of the pul* This was an external sonar microphone. I‘he sound signals are transmitted from the heart to the microphone through the fluid column of the catheter IFCT system).
Cardiovascular Research, The Chicago Medical School, and the Division of Cardiology This study was conducted during trnure of Hospital and ‘l‘he Chicago Medical School. and HE-5182 and with the aid of Research Grant HE-09350 of the National IHcart InstiService.
VOLUMI’. 19, FEBRUARY 1967
183
184
Kurz,
Slodki
Summary Case
NO.
and
Luisada
TABLE I of Data Obtained RRP. LV
RRP. RV
39 36 35 26 36 35 38 36 39 38
2,450 2,125 1,680 1,750 2,189 1,800 2,416 2,350 1,900 2,100
1,203 1,076 860 1,120 1,500 1,200 805 1,325 948 1,184
22 21 46 18 42 48 21
1,840 2,611 2,230 2,000
1,430 1,318 1,308 1,200
2;150 1,837
1;350 1,336
@IA
QpLV
Q-RV
Q-r
P’.
Q-IIA
CO
GI
SV
2,940 2,400 2,300 1,700 2,430 2,020 2,100 2,400 2,150 2,300
60 61 67 49 60 49 55 61 60 63
2,100 2,000 4,400 1,800 2,570 2,200 2,200
45 38 74 31 65 75 35
SI
A. Patients with Pure Mitral Stenosis 1 2 3 4 5 6 7 8 9 10
0.040 0.039 0.050 0.060 0.045 0.050 0.045 0.055 0.060 0.055
-_
0.060 0.060 0.095 0.100 0.049 0.070 0.080 0.065 0.068 0.063
0.058 0.060 0.090 0.090 0.060 0.090 0.070 0.080 0.085 0.079
_
0.354 0.387 0.398 0.387 0.365 0.394 0.387 0.361 0.370 0.375
0.380 0.380 0.380 0.420 0.360 0.380 0.378 0.392 0.365 0.370
4,880 4,000 3,800 3,170 3,950 3,080 3,450 4,000 3,700 4,100
B. Patients with Combined Lesions 11 12 13 14 15 16 17
0.060 0.080 0.060 0.060 0.060 0.070 0.055
0.080 0.140 0.080 0.090 0.095 0.080 0.045
0.080 0.120 0.080 0.090 0.085 0.110 0.080
0.393 0.334 0.348 0.311 0.411 0.411 0.394
0.378 0.360 0.352 0.340 0.390 0.390 0.400
3,100 3,400 7,100 3,080 3,930 4,600 3,500
Q-LV = Onset of Q wave to onset of left ventricular pressure in seconds; Q-RV = onset of Q wave to onset of right ventricular pressure in seconds; Q-IIA pr. = predicted Q-IIA interval according to rate in seconds; Q-IIA = Q-IIA interval found in seconds; CO = cardiac output in ml./min.; CI: cardiac index in ml./min./M.2; SV = stroke volume in ml.; SI = stroke index in ml/M.‘; RRP LV = rate of rise of pressure in the left ventricle in mm. Hg/sec. ; and RRP RV = rate of rise in the right ventricle. monary artery (wedge pressure) were recorded for Pressure traccalculation of the mitral valve area. ings from the ascending aorta, main pulmonary and right atrium were also artery, right ventricle Intracardiac phonocardiograms were obrecorded. tained in most patients from all chambers and vessels simultaneously with their respective pressure tracings, The in addition to the external phonocardiograms. sound tracings were recorded with a high pass filter having a nominal frequency of 100 c.p.s. and a slope of 24 db/octave. An electrocardiogram was recorded with all other tracings, usually lead II. However, one of the other standard leads was occasionally used for better definition of the QRS complex. Measurements: Pressures were determined in all the chambers entered. The mitral valve area was calculated using Gorlin’s formula in all cases of pure mitral stenosis and in most cases of mitral stenosis associated with aortic stenosis or insufficiency. The cardiac output was determined by the direct Fick method. Special Measurements: The following measurements were made: (1) time between the onset of the electrocardiographic Q wave to the onset of left ventricular and of right ventricular pressure pulses; (2) time between the onset of the Q wave and the onset of systolic rise of the first derivative of each ventricle;
(3) Q-I interval (interval between onset of the and the onset of the first rapid vibration of heart sound) ; (4) Q-IIA interval (onset of Q onset of the aortic component of the second
Q wave the first wave to sound).
The formula Q-IIA = 61.6 + 10.24 dR-R established by Shah and Slodki2 was used to determine the predicted Q-IIA interval for the heart rate of the patient*; (5) interval between the onsets of the right and left ventricular pressure pulses; (6) the maximal rate of rise of pressure in mm. Hgjsec. in each ventricle; and (7) the stroke volume and the stroke index. Statistical analysis was made of the data obtained.
RESULTS I n patients . interval the
between
onset
ranged 0.049
with
of the from
f
the left
0.039
0.002t)
pure
mitral
onset
of the
ventricular to
the and
pressure
0.060
(normal
stenosis, Cj wave
second interval
pulse (mean
averages
* Since it was impossible to eliminate AC interference from the electrocardiogram in several cases, the true duration of the QRS complex was determined in the routine electrocardiogram, taken prior to cardiac catheterization. t Standard error. THE
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Hemodynamics
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Stenosis
FK. 1. Z’atimt with pure mitral stmosi~, in whom the first sound iI-abr) has its onset before the onset of the right ventricular contraction. Silnultaneous pressures of right and left ventricles, exphonocnrdiogram (ext ternal PCG I, left ventricular phonocardiogram [IC (FCT) LV], right ventricular phonocardiogram [IC IFCT) RV], the first derivative of the left ventricle (1st D.LV) and electrocardiogram, lead 11 (ECG) are seen. AC artifacts are visible in the electrocardiogram and first derivative tracing. Left ventricular phonocardiogram shows the first (I), srcond (II) and fourth (IV) heart sounds, the opening snap (OS) and a presystolic murmur (PM). In the right ventricular phonocardiogram these phenomena are very faint or nonexistent. (Recording speed = 50 I~~IlL/SfX.,
abc
)
-r
0.039).3 The interval from the onset of Q to the onset of the right Lrentricular pressure pulse was between 0.049 and 0.100 second (mean 0.07 * 0.004) (normal interval averages 0.045).3 In patients with combined lesions, these intervals were longer, being from 0.055 to 0.080 second (mean 0.063 f 0.005) for the left ventricle and from 0.045 to 0.140 second (mean 0.081 f 0.009) for the right ventricle (Table IB). The mean difference of 0.056 f 0.005 for the left ventricle and of 0.075 * 0.009 for the right ventricle is statistically significant (lo < 0.05 and p < 0.02, respectively).* The onset of the first systolic wave of the first derivatives of left and right ventricular pressures was simultaneous with the onset of the respective pressure curve. The Q-Z interval was prolonged in all the cases studied, 0.04 to 0.12 second (mean 0.080 * in comparison with normal averages 0.004), The patients with combined lesions of 0.05.4 showed a higher average (mean 0.088 =t 0.006) than those with pure mitral stenosis (Table IB). These differences are statistically significant (t = 2.25, p < 0.05). In all cases studied, the rise of pressure in the left ventricle preceded * t test done comparing stenosis and that with with other lesions. VOLUME
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that of the right as it does in a nortnal heart.f The time difference between the two rises of pressure was 0.010 to 0.045 second (average 0.023 sec.) (Table I). The relation between Q-I and the onset of right ventricular pressure rise was variable (Table I). Only in some cases did the onset of the first sound coincide with the rise of right ventricular pressure (Case 2, pure mitral stenosis, (Table IA, and Cases 11, 13 and 14, combined defects, Table IB); in others, the onset of the first sound preceded the rise of right ventricular pressure (Cases 1, 3, 4, 7, 12 and 15, Table I)* In the remainder of the cases, the first sound occurred after the rise of right ventricular pressure. Figure 1 shows that the onset of the first sound precedes slightly the onset of the right ventricular pressure curve; the first component of the first sound (Ia) occurs before the onset of right ventricular pressure; the second and third components (It) and IC) occur early at the upstroke of the right ventricular pressure curve when the tricuspid valve is already closed. The Q-ZZA interval in patients with pure mitral stenosis was decreased ; in general, the Q-HA t This fact was observed even in a case of extremely severe mitral stenosis with right ventricular pressure at the level of systemic pressure (RV = 91/6-18) which was studied while this paper was being completed.
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Luisada
FIG. 2. Puttentwith mitral stenosis. The first derivative of the left ventricular pressure (1st D.LV) shows a phase of very slow rate of change (a-a) at the onset of ventricular systole, followed by a phase of very rapid rise. 1\C artifacts are visible in the electrocardiogram and first derivative tracing. (Recording speed = 200 mm./sec.)
interval in the group of patients with pure mitral stenosis (Table IA) was shorter than the predicted Q-IIA interval for that particular heart rate in 7 cases, and was larger in the remaining 3 patients of this group (Cases 1, 4 and 8, Table IA) ; however, these 3 patients had systemic hypertension, a fact that may account for the finding. In the patients who had mitral stenosis combined with another lesion, again the Q-IIA interval was decreased in the normotensive and increased in the hypertensive patients (Cases 12, 13, 14 and 17). The rate of rise of pressure in the patients with pure mitral stenosis was from 1,680 to 2,450 mm. Hg/sec. (average 2,092) in the left ventricle (normal 841 to 1,696, average 1,219 mm. Hg/sec.),5 and from 805 to 1,500 mm. Hg/sec. (average 1,134) in the right ventricle (normal 223 to 296, average 258 mm. Hg/sec.).5 In the group with combined lesions, the rate of rise of pressure was from 1,250 to 2,611 mm. Hg/sec. (average 2,039) in the left ventricle, and from 1,200 to 1,675 mm. Hg/sec. (average 1,373) in the right ventricle (Table IB). Therefore, there was not much difference between the two groups, both of which had mitral stenosis. Plotting of the Q-I interval against the stroke volume and stroke index in patients with pure mitral
stenosis suggests that a decrease in stroke volume is accompanied by an increase in the Q-I interval (r = -0.65 f 0.06). The Q-IIA interval in this group of patients, when plotted against the same parameters, shows a tendency to decrease except when arterial hypertension is present, in which case the Q-IIA interval increases. The behavior of the Q-I and Q-IIA intervals in the group of patients with combined lesions or aortic stenosis is similar to that of the patients with pure mitral stenosis (r = -0.89 f 0.07). If we compare our clinical data with those of Di Bartolo et a1.3 (in normal dogs), it is apparent that the intervals between the onset of the Q waves and the onset of the ventricular pressure rises lie in the upper limits of normal. Since in man the normal Q-I interval is slightly longer than in large dogs, our figures may still be within normal limits. The rate of rise of pressure in all our cases was significantly increased in both ventricles. In cases of pure mitral stenosis, two phases in the curve of the first derivative were observed: (1) a slow phase, which occurred while the mitral valve was still open; and (2) an extremely rapid phase after mitral valve closure (Fig. 1, 2). The first group of vibrations of the first sound THE
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Hemodynamics coincided kvith the rapid rise of the systolic wave of the first derivative and followed the early slow phase which does not exist in normal subjects.
The relation of the various phenomena that have their expression in the sounds and pressure changes detected by clinical and laboratory methods have been studied by various investigators. Frank,6 Wiggers’ and Starling and VisscherK emphasized the importance of the rate of change of pressure as an important and fundamental property of the heart muscle. Reeves et a1.,g and Gleason and Braunwald5 studied rate of change (first derivative or dp/dt) of the left ventricular pressure, and demonstrated that it has a direct relation to myocardial contractility and to the maximal tension potential of the ventricle at the onset of contraction. The relation of the heart sounds and their different components to the other phenomena was studied by Di Bartolo et a1.,3 Shah et al.,‘0 Sakarnoto et al.,ll and Mori et a1.,12 all in this laboratory. It was ascertained that the first group of vibrations of the first heart sound coincides with the rise of the early-systolic wave of the first derivative of left ventricular pressure and precedes its peak. This is true in both experilnental animals and man. Di Bartolo et a1.3 demonstrated in dogs that the normal first heart sound is recorded at a time when the atrioventricular valves are already closed, and that the production of this sound has no causal relation with the closure of the valves. The same was also found true in man without valvular lesions by observing the clinical tracings recorded in our laboratory (some of the patients had flow murmurs and no lesions of the valves). Apparently, the rise of pressure of the left ventricle is responsible for accelerations and decelerations of blood that cause a vibration of the entire system of valve leaflets, chordae, septum, free cardiac walls, blood and vessels and, hence, for the production of the first sound. These findings were confirmed by van Bogaert et a1.13 and by Piemme et a1.14 Since there is no abnormal delay between onset of the electrical activity of the ventricle (Q wave) and onset of the mechanical activity (onset of pressure rise), the delay of the first sound in mitral stenosis might seem connected with the delay in mitral valve closure, because the valve will not close until left ventricular pressure has reached and surpassed the level VOLUME
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of left atria1 pressure. However, further considerations will be presented later which will modify this statement. After a slow beginning, the rate of rise of pressure in the left ventricle is increased in cases of pure mitral stenosis (Fig. 1, 2) ; in this lesion the mitral leaflets and the mitral ring are more rigid than in normal subjects. This rigidity decreases the bulging of the valve leaflets into the left atrium which normally occurs during- isovolumic contraction,15 and tends to increase the rate of rise of pressure and therefore the loudness of the first heart sound. The pattern of the first derivative of left ventricular pressure was found significantly altered in mitral stenosis (Fig. 2). It showed at first a slow rise during the first part of isovolumic contraction (a-a)? revealing that the left ventricular tension could not rapidly increase until the level of left atria1 pressure had been reached; thereafter, a very rapid rise occurred. Jll mitral stenosis, the entire left ventricular onusculature is already contracting at the time of mitral valve closure, as evidenced by the normal interval between Q and onset of left ventricular pressure and the prolonged Q-I; this sequence should be compared with the normal sequence of events because, in the normal heart, the mitral valve closes first, and then the left ventricular fibers gradually start to contract.“’ In mitral stenosis, the left ventricle starts contracting while the mitral valve is still open. This sequence of events, which causes an initial slow rise of left ventricular pressure (revealed by the initial portion of the first derivative), seems to be an additional factor for the late but extremely rapid rise of pressure and for the loud and delayed first heart sound. The increase in the rate of pressure rise in the right ventricle may be explained by the right ventricular hypertrophy typical of mitral stenosis. As pointed out before, the relation between the first heart sound and the right ventriculqr pressure curve was variable in our studv. The first component of the first heart sound ‘in some of our cases occurred before the onset of the right ventricular curve; the second and third components of the first heart sound occurred at a time when the tricuspid valve was already closed. These facts suggest that, as we previously demonstrated in the normal heart, the right ventricle does not contribute appreciably to the first heart sound, even in cases of mitral stenosis. This view is in contrast with that of Leo and Hultgren,‘7 who thought
Kurz,
188
Slodki and Luisada
that a “tricuspid” component preceded a “mltral” component of the first sound in cases of mitral stenosis. The unimportant contribution of the right ventricle is further substantiated b) the fact that the first sound is well recorded in the left ventricular cavity and only barely demonstrable in the right ventricular phonoIt is further confirmed by recent cardiogram. experiments of this laboratory with right heart bypass,18 demonstrating a persistence of the various components of the first heart sound. %JMMARY
Seventeen patients with mitral stenosis were studied by right and left cardiac catheterization. intracardiac phonocardioPressure tracings, grams, cardiac outputs and valve areas were determined ; several measurements were made. The data indicate that: (1) the first sound is delayed ; (2) following an initial slow rise, the rate of rise of pressure of the left ventricle is sharply increased ; and (3) the rate of rise is The inincreased in the right ventricle also. crease of the maximal rate of rise of ventricular pressure in pure mitral stenosis is explained by the lack of early systolic bulging of the mitral leaflets into the left atrium and by the fact that closure of the mitral valve occurs during left ventricular contraction, not before it, as in norOn the basis of simultaneous inmal subjects. tracardiac phonocardiograms in the left and right ventricles, it is suggested that the right ventricle contributes little to the first heart sound, as recorded from the surface of the chest, even in cases with mitral stenosis. It is further shown that a decrease in stroke volume will increase the duration of the Q-I interval and decrease the duration of the Q-HA
3.
4.
5.
6. 7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
interval. REFERENCES 1. LIJISADA, A. A., MACCANON, D. M. and SLODKI, S. J. Intracardiac phonocardiography. Description of a new simplified system. Circulation, 32: 563, 1965. 2. SHAH, P. M. and SLODKI, S. J. The Q-II interval: .4 study of the second heart sound in normal
17.
18.
adults and in systemic hypertension. Circulation, 29: 551, 1964. Dr BARTOLO, G., NUNEZ-DEY, D., MUIESAN, G., MACCANON, D. M. and LUISADA, A. A. Hemodynamic correlates of the first heart sound. Am. J. Physiol., 201: 888, 1961. SAKAMOTO,T., KAITO, G. and UEDA, 1~. Electrocardiographic and phonocardiographic studies in hypertension. II. Phonocardiographic study with special reference to the atria1 sound and “Q-I” interval. Ja#. Heart J., 1: 213, 1960. GLEASON, W. L. and BRAUNWALD, E. Studies on the first derivative of the ventricular pressure pulse in man. J. Clin. Invest., 41: 80, 1962. FRANK, 0. Zur Dynamik des Herzmuskels. Ztschr. B&l., 32: 370, 1895. WIGGERS, C. 3. Some factors controlling the shape of the pressure curve in the right ventricle. Am. J. Physiol., 33: 382, 1914. STARLING, E. H. and VISSCHER,M. B. The regulation of the energy output of the heart. J. Physiol., 62: 243, 1927. REEVES, T. J. et al. The hemodynamic determinants of the rate of change in pressure in the left ventricle during isometric contraction. Am. Heart J., 60: 745, 1960. SHAH, P. M., MORI, M., MACCANON, D. M. and LUISADA, A. A. Hemodynamic correlates of the various components of the first heart sound. Circulation Res., 12: 386, 1963. SAKAMOTO,T., KUSUKAWA, R., MACCANON, D. M. and LUISADA, A. A. Hemodynamic determinants of the amplitude of the first heart sound. Circulation Res., 16: 45, 1965. MORI, M., SHAH, P. M., MACCANON, D. M. and LUISADA, A. A. Hemodynamic correlates of the various components of the second heart sound. Cardiologia, 44: 65, 1964. VAN BOGAERT, A. et al. Contribution 1 1’ Ctude du premier bruit du coeur normal. Arch. mal. coeur, 55: 368, 1962. PIEMME, T. E., BARNETT, G. 0. and DEXTER, L. Relationship of heart sounds to acceleration of blood flow. Circulation Res., 18: 303, 1966. CHAILLET, J. L. Cineradiography of Cardiac Valves Utrecht, 1965. Drukkerij J. & D. van in Man. der Horst. SARNOFF, S. J. and MITCHELL, J. H. The regulation of the performance of the heart. Am. J. Med., 30: 747, 1961. LEO, T. and HULTGREN, H. Phonocardiographic characteristics of tight mitral stenosis. Medicine, 38: 85, 1959. LUISADA, A. A., KURZ, H., SLODKI, S. J. and MACCANON, D. M. Normal iirst heart sounds with nonfunctional tricuspid valve or right ventricle. Ciwulation, in press.
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