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The effects of supine exercise on left ventricular volume in heart disease
The effects of supine exercise on left ventricular volume in heart disease J. David B&tow, M.D.* Frank E. Kloster, M.D. Cyrus Farrehi, M.D. Michael T. H. Brodeur, M.D. Richard P. Lewis, M.D. Herbert E. Griswold, M.D. Portland, Ore.
T
he effect of exercise on cardiac volume has interested investigators for many years. Several have studied the influence of exertion upon total heart volume in healthy subjects by radiographs, and the results have been variable for exercise both in the supine and sitting positions.‘-j Determination of total heart volume provides only an indirect estimate of individual chamber volume, however, and more complete understanding of the cardiac adaptation to exercise is aided by specific knowledge of changes in left ventricular size. Such measurements have become available from animal investigations in recent years. In the anesthetized dog, Chapman, Baker and Mitchell6 used an angiographic method and found a decrease in left ventricular end-diastolic and endsystolic volumes with electrically induced exercise. Rushmer, Smith and Franklin’ found decreases in left ventricular dimensions in the unanesthetized exercising dog, and also demonstrated that ventricular emptying was more complete during exercise. From the This study Received *Address: Ore.,
319
Division of Cardiology, Department was supported by United States for publication May 13, 1965. Department of Medicine, University 97201.
These effects of exercise in man have been the subject of two recent investigations. Changes in left ventricular dimensions with exertion were described by Braunwald and his associates.8 In 4 patients, silver clips were sewn to the left ventricle at the time of mitral commissurotomy or closure of an atria1 septal defect. After convalescence of the patients, cineradiographic analysis of the movement of the clips showed average decreases of 6.5 and 5.1 per cent, respectively, in left ventricular end-systolic and end-diastolic dimensions with exercise. Paley and Leonard9 studied left ventricular end-diastolic volume in 6 normal volunteers by the thermodilution method. With exercise which caused more than a twofold increase in the cardiac output, stroke volume rose but left ventricular end-diastolic volume did not change. In these patients, more complete emptying occurred from a left ventricle of unchanged diastolic size. The purpose of this report is to describe measurements of left ventricular volume
of Medicine, Public Health of Oregon
University of Oregon Medical Service Program Project Grant Medical
School,
3181
S.W.
School, Portland. No. HE 06336-03.
Sam Jackson
Park
Rd.,
Ore.
Portland,
changes with heart disease.
exercise
in 30 patients
with
REST
EXERCISE
Fs"/EDV:?O?~ EDV~235ml/M'
FS"IEDV 27% FDV:I59ml/M"
Method The thermodilution method for estimation of left ventricular volume has been described previously. lo*11 In this study the left ventricle was catheterized by the percutaneous transseptal method from the right femoral vein, and the left brachial artery was cannulated with polyethylene tubing. From the right femoral artery a retrograde catheter with a very small bead thermistor* at the tip was positioned just above the aortic valve. Determinations were made in all patients during a steady state at rest and during the fourth through sixth minutes of exercise. Seventeen patients pedaled a bicycle ergometer at a constant rate with the left leg, with resting measurements recorded after the foot was positioned on the pedal. The other 13 patients raised and lowered the left leg to a regular count, approximately 20 times per minute. Recordings were made of the electrocardiogram and left ventricular and brachial arterial pressures, and the cardiac output was measured by indocyaninegreen dilution. Oxygen consumption was determined in most patients by Scholander analysis of expired air. 1,lultiple thermodilution curves were produced by rapid injections of 5 ml., or rarely 10 ml., of cooled saline into the left ventricle. The changes in the temperature of aortic blood thereby produced were detected by the aortic thermistor (Fig. 1). By dividing the cardiac output by the heart rate, forward stroke volume (FSV) was determined. From the average downslope characteristics of the thermodilution curves, the ratio of FSV to ventricular end-diastolic volume (EDV) was obtained. Using FSV and this ratio (FSV/EDV), ventricular end-systolic volume (ES%‘) and the EDV were calculated.“J3 The formulas are :
(1) where tween *Victory
FSV/EDV
=
I-
y
Tn and Tn+l are differences bethe base-line temperature of aortic Engineermg
Corp..
Union,
N. J.
Fig. 1. Duplicate thermodilution curves at rest and during exercise in Patient 9. A decrease in the temperature of aortic blood is shown as an upward deflection. An average ratio of differences in temperature in the downslopes of the curves and a linowledge of stroke volume enabled us to calculate ventricular volume. In this patient who had aortic insufficiency the proportion of the end-diastolic volume ejected as the forward stroke volume averaged 20 per cent in three curves at rest and 27 per cent in three curves obtained during exercise. Enddiastolic volume decreased. FSV: Forward stroke volume. ED V: End-diastolic volume. The electrorardiogram is above.
blood and that found at beats n and n+l at end-diastole in the thermodilution curve
(3)
ESV
=
EDL‘
--
FSV
In the presence of aortic insufficiency the calculated ESV includes both the aortic regurgitant volume and the true ESV, because the indicator contained in the regurgitant volume contributes to the next end-diastolic ventricular concentration of indicator and is treated mathematically as though it had not left the ventricle in the preceding systole. Mitral insufficiency theoretically invalidates the method and no patients with this lesion were studied. The Teflon catheter employed for left ventricular catheterization is 70 cm. long, has four side holes located within 1.5 cm.
Volume Number
71 3
Efects
of supine exercise on L V volume in heart disease
of the tip, and is size 8MF. It was connected to a P23Gb strain gauge* by a 92-cm. length of nylon or Teflon tubing with a lumen diameter of 1.85 mm. Thirty patients with sinus rhythm were studied and the diagnoses in each are listed in Table I. The subjects presented a wide spectrum of severity of illness. Those with aortic valve prostheses and those who had undergone open commissurotomy for congenital aortic stenosis had few or no symptoms, whereas some with aortic valve disease were severely handicapped. No patient had evidence of retention of fluid at the time of the study, but congestive failure had been present previously in several. Three patients had clinical and angiocardiographic evidence of left ventricular hypertrophy without valvular disease. One of these had mild systemic arterial hypertension and a small systolic pressure gradient across the outflow tract of the left ventricle. The size of the cardiac silhouette in standard posteroanterior chest radiographs was determined by the method of Schwarz.14 This measurement provides a correction for body size and expresses frontal heart area as a percentage of predicted normal. Occasionally, the exact end-diastolic time for the measurement of pressure in the left ventricle was not apparent from inspection of the record, and the pressure 0.05 second after the onset of the QRS complex was used.15
The complete results are presented in Table I, and thermodilution curves from a patient are shown in Fig. 1. The results for voIume and flow were corrected for body size and expressed per square meter of body surface area (M.2). The presence of the tip of the transseptal catheter in the left ventricle during exercise did not produce important problems. In some cases, premature beats developed at the onset of exercise but disappeared when the catheter was moved slightly. Evaluation of the method. The frontal heart area from chest radiographs was compared with the EDV at rest (ml./M.2). The correlation coefficient was 0.75. One *Statham
Transducers.
patient with right ventricular enlargement due to an atria1 septal defect was excluded from this comparison. The reproducibility of the thermodilution curves was appraised in all patients during rest and exercise. At rest, 111 curves were obtained in the 30 patients, an average per patient of 3.7 curves. The downslope function (Tn + l/Tn) of each curve was compared to the average of downslope functions from all curves in that patient as follows: Average
downslope, in patient (Average
Inc.,
Hato
Rey.
Puerto
Rico.
all c”rves
downslope,
all curves
in patient)
At rest, the mean difference of individual curves from the average for the patient in whom they were obtained was 2.4 per cent without respect to sign (S.D. = 2.3 per cent). With exercise there were 107 curves, an average of 3.6 per patient. The mean difference of the downslope function for a given curve from the average for the patient was 3.5 per cent (S.D. = 3.4 per cent). The consistency of the exponential downslope of the individual curves was similarly analyzed. At rest, 387 pairs of downslope temperature “steps” were employed in the calculation of left ventricular volume, each curve providing an average of 3.5 pairs or ratios. The variation of each ratio from the average of downslope ratios for the curve was calculated : Average of downslope ratios for the curve
Results
321
(Average
> of downslope
_
Individual downslope ( ratio of the curve ratios for the curve)
>
X 100 = y. variation
At rest, the mean difference for a single downslope ratio from the averagg for the curve was 3.7 per cent, without +egard to sign (S.D. = 3.4 per cent). With exercise there were 401 downslope ratios, with an average of 3.8 per curve. The mean difference for any individual ratio from the average for the curve was 3.9 per cent, without respect to sign (SD. = 4.0 per cent). Marked changes from the ratio of FSV/EDV at rest did not often occur with exercise; two of the greatest were from 0.30 to 0.38 in one patient, and from 0.20 to 0.27 in another. Changes in the EDV were usually in the same direction as
322
Mristoz~‘, Kloster.
E;ctrrehi, Hroderrr,
Postoperative Aortic Valve Dise;lse 1. 45 1 100
L\‘H
I,ewz.s, llnd Griswold
Rest Eser. Rest Exer. Rest Exer. Rest Exer. Rest her.
2.
57
2
136
ST-T
.z.
51
1
110
L\‘H
4.
52
2
110
S’L’I
.5.
18
1
100
Normal
6.
13
1
101
LVH
Rest
7.
19
1
106
LVH
Excr. Rest Excr.
2
125
LVH
Aortic Insufficiency 8. 20 9.
51
2
150
L\TH
10.
19
2
165
L\:H
11.
41
2
130
LVH
12.
19
1
101
LVH
13.
54
2
136
L\‘H
14.
37
2
102
LVH
1.5.
32
1
136
L\!H
16.
42
2
135
17.
16
3
148
LI’H
18.
22
2
127
LVH
19.
42
2
156
IIBRB
20.
41
2
111
Normal
Rest Exel-. Rest Exer. Rest her. Rest Erer. Rest Exer. Rest Exer. Rest Ger. Rest EXN.
Aortic Stenosis and Insufficiency 21. 21 1 110
Rest Exer. Rest E:xcr. Rest Exer. Rest her. licst Eser.
L\W
Rest Exer.
Rest E:\er. IiCht t*:Wi-. Rest thei-.
22.
30
2
100
L\;H
23.
46
3
1.36
L\.H
24.
53
3
127
LVH
120 362 137 3.Z1 I i7 118 262 148 318 136 .%92. 152 .w 153 352 170 170 422 15’) 392 110 .15.5 35’, 154 318 1.57 271 1.54 296 148 170 3.13 I54 .ZhS 170 342 I 34
1-t’)
91 7x 9.3 71 8.5 76 96 83 107 68 140 108 120
2.28 2 7.5 3 02 3.79 3 70 .1.98 2 54 4.37 3.26 4.80 2.34 6.00 2.98 3 33
78 96 70 83 77 1ti 86 102 X8 100 68 9.z 68 90 70 114 68 84 81 90 87 120 78 102 92 108
3.71 3 95 3.27 3.54 4.35 5.99 2.62 3.18 2 77 2.99 1.95 3 22 2.80 .Z.lO 3.12 4.05 .z ,69 4.40 ,z 14 3.85 3.17 2.88 2.70 3.11 .Z.68* 5.12*
78 102 77 93 80 02 66 90
3 .99* 1.92* 3.02 4.19 1 49 2.12 1.88 2.45
if)
*Cal-disc output determined by the Fick principle. L1.U: Left ventricular hypertrophy. ST-T: Nonspecific S-7 segment and ‘T-wave abnormalities. KliHB: Right E.5’1’: End-systolic volume. CHF: Congestive heart failure. T’S: l’ricuspid stenosis. ..ll: .\ortic insufficiency. In the electrocardiogram, LVH was diagnosed when the R wave in Lead Va and the S wa\~ in Lead VI or Lead
bundle branch block. AS: Aortic stenosis. Vz totaled 35 mm. or
Volume Number
71 3
FSV (mlJM.2)
EDV (rd./M?)
ES V and regurgitant volume (ml./M.2)
Efects
of supine exercise on L V volume in heart disease
FSV gD>
-___-
Pressures (mm. Hg) Comments
Left
Central
ventrkle
aorta
30 30 39 41 52 47 33 46 39 45 34 43 28 28
100 88 130 108 100 85 106 164 115 122 87 113 165 140
70 58 91 67 48 38 73 118 76 77 53 70 137 112
.30 .34 .30 .38 .52 .55 .31 .28 .34 .37 .39 .38 .17 .20
128/a 176/7 150/13 192/l 7 125/s 182/18 125/3 170/4 127/10 130/5 120/25 150/22 148/10 160/10
48 41 47 43 56 51 30 31 31 30 29 35 41 34 43 36 54 52 39 39 36 24 35 31 40 47
218 172 235 159 373 268 176 163 163 150 181 167 186 155 187 190 186 179 216 216 180 171 206 206 108 104
170 131 188 116 317 217 146 132 132 120 152 132 145 121 144 154 132 127 177 177 144 147 171 175 68 57
.22 .24 .20 .27 15 :19 .17 .19 19 :20 .16 .21 .22 .22 .23 .19 .29 .29 .18 .18 .20 .14 17 :15 .37 .45
125/3 145/l 152/19 175/25 120/17 165/16 155/26 165125 125/13 150/10 175/17 215/21 130/14 160/16 118/6 175/18 135/l 1 170125 125/7 145/12 132/l 150/8 130/l 1 175/12 125/s 180/16
51 48 39 45 19 23 29 27
124 130 108 145 173 121 116 104
73 82 69 100 154 98 87 77
.41 .37 .36 .31 11 :19 .25 .26
180/12 190/15 144/7 168/6 170/44 160/36 230/31 280/34
LAD: ASD: more.
323
Left axis deviation with frontal QRS axis above Atria1 septal defect. with or without ST-T abnormalities.
minus
30 degrees.
Brachial artery
112/68 -
120/‘72 172/‘94 138i68 194196 95/50 162/80 110/70 145,‘88 142/80 165/85 lOS/SS 140/80 128/75 140,/88
S/SO 110/75 90/B 125/80
-
prosthesis
Aortic
prosthesis
Aortic
prosthesis
Aortic
prosthesis
Postoperative
AS, slight
AI
Postoperative
AS, slight
AI
Postoperative
.kS, slight
Al
145/60 185/85 165/45 CHF 185/60 168/45 Mean 132 142/73 1 so/so 140/70 170185 180/50 CHF 215/65 135/.55 ? CHF 185/65 138/55 200,BS lSOj60 .\nemia 175175 Mean 70 125/65 CHF 135/60 140/‘40 183/65 130/70 Slight 190,/90
155/50 125/45 132/78 120/75 170/50 130/60 118,‘60 150/60 1 lo/65 125/75 -
125/78 96/56 123/60
120/73 135/80 112/54 120/76 135/58 150/70 176/72 220196
156/68 -
FSV:
Aortic
Forward
stroke
TS,
volume.
in past
in past in past
(hematocrit
in past
AI
CHF
in past
CHF
in past
CHF
in past
EDV’:
28)
End-diastolic
volume. Conlinued.
7’able I .--- Cont’d.
I
I
I
I
Idiopathic 25.
Left 14
Ventricular 1
26.
41
2
100
LAr)
27.
41
2
111
LVH
5.5
2
130
RVH
29.
44
2
118
P mitrale
30.
20
2
10.)
Normal
Miscellaneous 28.
Hypertrophq 86
I LVH
changes in FSV. In the formula for EDV, it is apparent that this might be expected, since FSV is one of the components in the calculation of EDV. However, it is emphasized that the calculation of EDV depends both on FSV and FSV/EDV, and that these were independent measurements. There were examples in which EDV and FSV varied in opposite directions. Exercise in patients aff.er aortic valve surgery. In terms of physiologic handicap for the left ventricle, these 7 patients were the closest to normal of the entire group. Studies by indicator-dilution methods from several laboratories have shown the normal EDV at rest probably to be below 135 ml. per square meter,gJlJ6J7 and in only 1 patient in this group was this value exceeded at rest. In 4 patients the EDV fell 12 to 15 per cent with exercise, and the ESV also decreased. Changes in FSV were variable. In the other 3 patients, EDV rose with exercise, and definite increases in FSV were associated (15 to 39 per cent). Aortic insuficiency. There were 13 patients with aortic insufficiency of varying grades of severity, and in 12 of them the EDV at rest was distinctly abnormal. EDV decreased with exercise in 10 patients, although in only 4 was the change
I Rest Exer. Rest Exer. Rest Exer.
178 297 151 3.58 161 3 l,<
123 144 105 135 66 90
4.04 4.50 2.46 2.39 2.99 4.14
Rest Exer. Rest Exer. Rest Exer.
143
98 115 72 126 76 102
2.54 3.26 2.38 2 66 4 34 5 56
133 289 287
large. The average decrease was 13 per cent (range from 4 to 32 per cent). In of alteration of general, the direction FSV and of EDV was similar, but 3 patients had a rise in FSV associated with a smaller EDV. Three patients in this group had either no change or an insignificant change in the EDV. No patient in the group with aortic insufficiency developed a definite or large increase m EDV with exercise, despite the fact that some had severe disease. There was no apparent correlation between the clinical state of disability and the degree of response of the EDV to exercise. The methods employed do not provide a measure of total left ventricular stroke volume when aortic insufficiency is present, and thus the true ESV could not be determined in this group. Remaining grou$s. No consistent pattern was observed although there was a tendency for FSV and EDV to vary together. The most severely ill patient in the entire study had a decrease in EDV and a rise in FSV with exercise (Patient 23). The 3 patients with idiopathic left ventricular hypertrophy had a decrease in ES\’ and EDV with exercise.
Volume Nwmber
FSV (ml./M.2)
71 3
Efecb
ED V (mlJM.2)
ESV and regurgitant
volume (ml./M.2)
of supine exercise on L V volume in heart disease
325
(mm. Hg)
Pressures FSV
Comments
-EDV
Central
Left vent&e
Brachial artery
aorta
~
~
33 31 23 18 45 46
137 103 88 60 107 104
104 72 65 42 62 58
.24 .30 .26 .30 .42 .44
115/s 125/7 165/16 190/28 100/7 125/12
110/85 155/115 100/65 -
130/85 150/100 165/108 200/120 120/65 135/G
26 28 33 21 57 55
72 85 127 75 139 134
46 57 94 52 82 79
.36 .33 .26 .28 .41 .41
130/13 150/25 120/4 140/l lOO/ll 120/12
-
140/88 155/85 lZS/SO 160/98 115/65 135/80
End-diastolic volume-end-diastolic pressure relationships. There was no consistent relationship between end-diastolic pressure (EDP) and EDV when patients were compared at rest. Some had a definitely abnormal EDP with a normal EDV. Changes in EDV and EDP were most often in opposite directions during exercise. The most common pattern was a decrease in EDV associated with an increase in EDP during exertion. In only 9 of the 30 patients did EDV and EDP definitely change in the same direction. Discussion Changes in end-diastolic volume with exercise. From animal experiments and previous papers concerning exercise in man, we anticipated certain types of responses but did not consistently observe them. We expected that patients with gross cardiomegaly, abnormal EDP, and perhaps those with low cardiac output at rest would have further enlargement of the EDV with exercise, as has been suggested previ0us1y.~ Instead, we often found decreases in EDV with exercise in those with the largest ventricles at rest. Only limited generalization from this point is possible because all those in the present study with
110/70 -
Systemic hypertension
Secundum ASD Mitral
stenosis
Mild mitral stenosis
the most severe diseasehad some degree of aortic insufficiency. It is possible that tachycardia and perhaps other factors result in a decrease in the proportion of the stroke volume which regurgitates during exercise, and a smaller EDV might occur.18Jg This explanation is suggested in 7 of the patients with aortic insufficiency who had an increase in FSV/EDV with exercise. The fact remains, however, that EDV decreased with exercise in patients with severe heart disease due to aortic insufficiency, some of whom had had congestive heart failure. With important aortic insufficiency, the ratio FSV/EDV is low, and minor variations or errors in the measurement will produce relatively large changes in the calculated EDV, for a given FSV (see Formula 2). However, this factor is not believed to be the explanation of the changes in the aforementioned patients, since multiple thermodilution curves were analyzed in each patient, because the changes in EDV were reasonably consistent in the aortic insufficiency group, and because the major changes with exercise were of FSV in some patients rather than of FSV/EDV. In view of past work we anticipated that the postoperative patients without
a gross handicap for the ventricle would have either a decrease in El)\. \vith exercise or no change. Those who had a smaller ESV and ED\,’ with the same or larger FS\’ lvith exercise demonstrated this expected normal response with more cotnplete emptying. However, the findings in 3 other patients in the postoperative group and 2 other patients (Patients 22 and 28) suggest that the abnormal heart \vith a normal EDV at rest ma\: show an increase in the EI>V with exercise. If this is the case, a higher FSV will very likely be associated. Whether this response is abnormal is not knobvn, since no patients in the present study could be considered to be entirely free of heart disease. Other studies of cardiac performance suggest that a larger ED\: with exercise need not be abnortnal. Occasional increases in left ventricular diameter in the dog during exertion \vere described by Wilson.?” It also has been shown that FSV may rise remarkably during exercise in healthy people, and it is possible that a normal increase in the proportion of ventricular emptying might not be sufficient to account for the degree of rise observed in FS\;. Thus, an increase in EDV would be required. For example, in studies of healthy subjects \vho exercised in the upright: posture to the tnaximunt possible oxygen consumption, _\Iitchell, Sproule and Chapntan2t found that the average FSV doubled. If the normal left ventricle at rest were 40 to 60 per cent emptied by each systole, which is a reasonable estimate, an increase in EDV would surely be necessary to provide a twofold increase in stroke volume, even if ventricular emptying were remarkably complete with exercise. The more complete the etnptying at rest, the more likely that EDV would increase with exeriise, if FSV were to increase greatly. This observation is not entirely analogous to our study, hobyever. Our patients \vere in the supine position, and the decreases in heart volutne and FSV known to occur with assumption of the erect posture provide a different base line for comparison.22-27 Furthermore, in our patients who had an increased EI>\jT with exercise the increase in FSV was not of such great magnitude. Finally, the level of exercise in our stud>,
~;ts consideral)I~- short of t tw nt;txintulll ox\.gen cotisuittption. For t lw present I ttoivever, \v~ I~;ive concluded that ;L normal resting left ventricular I:I)\’ \vhich ittcreases \\.itlt exercise ttt;t>’ not consti tutc abnormal response, \\ hen significant at1 increases in F’S\’ ;trc’ :tssociated. When consideration is given to the several factors \vhich could influence left ventricular votuttte, it perhaps is not too surprising th;tt the values found were not more often predictable. These influences might include right ventricular performance, the volume and pressure of the filling reservoir for the tcft heart, inotropic effects on left ventricular performance, and the impedance to left ventricular outflow. linti tnore exact nteitns are available for accurateI>- quantifying contractile force of the left ventricle in intact patients. the relative intportancc of any one of these influences tnay remain uncertain. EDP-EDI- relationships. The lack OS a consistent relationship between left ventricular El)l’ and EI)j‘ is of theoretical interest and practical importance. I’ublished nork clearly relates the end-diastolic length of a vent&ular ntuscle segment to EI)I’ in a consistent manner in the dog.“” In addition, the relationship between the length of ;I segment of left ventricular muscle and El)1 is ;i predictable one, Lvhen studied at the titrte of thoracotom>~ in patients with mitral stenosis and atria1 fibrillation.‘!’ \‘entricular muscle segmettt length varies in the same direction with ED\‘, and therefore a consistent relationship was expected between El)\- and El)I’. ‘This did not always obtain in our patients during exercise. When EI)T’ and EI)V changed itt the Sante direction, our observations were consistent \vitlt published experimental data. ttt most instances, however, EI>I’ and EDI7 moved in opposite directions, contrary to the concept of a consistent pressure-volume curve for the left ventricle at end-diastole. Several aspects of the exercise response were considered in searching for an explanation. Alarked tachycardia increases the intpedance to ventricular filling in the experimental anitnal, perhaps because of incomplete ntuscular relaxation.3’1-a:i ‘l’achg;cardia has also been ioutd to have thw effect in the humatt hwrt, but ottl>, with
Volume
Number
71
3
Efects
of supine exercise on L V volume in heart disease
very short diastolic periods, when studied at the time of surgery in patients with mitral stenosis.2g However, the changes in heart rate in our patients were not extreme, and we are forced to conclude that the effects of heart rate alone on the ventricle in diastole do not explain the changes observed. The effects of sympathetic nervous system activity or circulating catecholamines have been reported variously to decrease impedance to ventricular filling,31 not to change diastolic pressure-volume (or muscle segment length) relationships,32-34 and to increase diastolic left ventricular impedance.35 In view of these reported variations, it is not possible to conclude with certainty what effects would be expected from these influences in our patients with abnormal hearts. There have been reports in recent years suggesting that the physical properties of the ventricle are altered by left ventricular hypertrophy. The outstanding example is idiopathic hypertrophic subaortic stenosis, in which the left ventricular cavity volume is small, the wall is thick, and left ventricular EDP is often elevated. From such findings it has been concluded that the diastolic compliance of the ventricle is reduced, resulting in a higher EDP for a given EDV. 36-38The concept of low ventricular compliance helps to explain the lack of correlation of EDP and EDV values obtained in patients at rest. However, if alterations in compliance alone were involved, then consonant changes along this new pressure-volume curve with exercise would still occur, and this wTe seldom observed. However, the compliance characteristics (elastic factors) of the ventricle are not the only determinants of diastolic ventricular pressure, as Dodge39 has pointed out. The resistance components (viscous factors of blood and ventricular wall) are usually overlooked in view of the geometry of the ventricle, the short distance ventricular blood travels in diastole, and the large ratio of volume to surface area of the chamber. But the resistance component of ventricular muscle determinant of may be an important EDP in some patients, since its effect is proportional to the rate of change in diastolic ventricular volume. It could be
327
postulated that changes in ventricular compliance are associated with forceful atria1 contraction when left ventricular hypertrophy is present,4O and that an accelerated rate of contraction by the left atrium during exercise magnifies the effects of the viscous resistance to left ventricular distention, a rate-dependent function. This influence which increases EDP could overshadow the opposite effect on pressure of a smaller volume and thereby produce the results that we found in many patients, a smaller EDV and a higher EDP. Other factors are undoubtedly of importance also. It is recognized that the left ventricular pressures that we measured were not the transmural or effective distending pressures, since no intrapericardial or intrapleural reference pressure was available. It does not seem to us to be likely that changes in intrapleural pressure could account for all of the variability of the changes in EDV-EDP relationships, but such changes represent an unpredictable, perhaps important factor. Alterations in intrapericardial pressure would be especially important if changes in volume of other intrapericardial chambers occurred and the pericardium were not distensible. Work by Rapaport and associates4r is of considerable interest in this regard. They measured right ventricular volumes by thermodilution in patients with heart failure. In five of six instances, right ventricular EDV rose with exercise. Intrapericardial pressure could be altered by such changes, thereby altering the measured or absolute left ventricular diastolic pressure in an unpredictable manner. Regardless of the factors responsible, we believe that it is evident from our results that the EDV (or muscle fiber length) could not be consistently predicted from the EDP at rest or with exercise in our patients. Furthermore, the ability of the abnormal left ventricle to change its EDV in a given direction could not be determined from the EDP. Thus, we believe that EDP, as routinely measured during cardiac catheterization in man, cannot be used alone as an assessment of the adequacy of the cardiovascular response to exertion by the abnormal heart. It also follows that changes in left atria1 pressure or pulmonary capil-
lary pressure are not consistently valid reflections of changes in left ventricular EDV. Summary Left ventricular end-diastolic volume (EDV) was measured by thermodilution in 30 patients with heart disease. Those with little physiologic abnormality varied in their response to exertion. In some, EDV decreased while forward stroke volume (FSV) was maintained or increased. In others, EDV and FSV rose during exercise. Patients with aortic insufficiency usuall) had a decrease in EDV with exercise, whether FSV increased or decreased. In patients with other lesions, FSV and ED\‘7 tended to vary together. Changes in EDV and left ventricular end-diastolic pressure with exercise were usually not in the same direction, and the factors which may explain this unexpected finding are discussed. It is concluded that end-diastolic pressure, as usually measured in the left ventricle during cardiac catheterization, will not reliably describe EI)\: or its changes with exercise. We helpful
are indebted discussions
to Dr. Benjamin during preparation
Ross for his of this paper.
9.
10.
11.
12.
13.
14.
15.
16.
REFERENCES 1.
2.
\3
4.
5.
6.
7.
8.
Meek, W. J., and Eyster, J. A. E.: Cardiac size and output in man during rest and moderate exercise, Am. J. Physiol. 63:400, 1923. Liljestrand, G., Lysholm, E., and Nylin, G.: The immediate effects of muscular work on the stroke and heart volume in man, Skandinav. Arch. Physiol. 80:265, 1938. Kjellberg, S. R., Rudhe, U., and SjGstrand, ‘I‘.: The amount of hemoglobin (blood volume) in relation to the pulse rate and heart volume during work, Acta Physiol. Scandinav. 19:152, 1949. Ruosteenoja, R., Linko, E., Lind, J., and Sollberger, A.: Heart volume changes at rest and during exercise, Acta Med. Scandinav. 162:263, 1958. Holmgren, A., and Ovenfors, C. 0.: Heart volume at rest and during muscular work in the supine and sitting position, Acta Med. Scandinav. 167:267, 1960. Chapman, C. B., Baker, O., and Mitchell, J. H.: Left ventricular function at rest and during exercise, J. Clin. Invest. 38:1202, 1959. Rushmer, R. F., Smith, O., and Franklin, D.: Mechanisms of cardiac control in esercisr, Circulation Res. 7:602, 1959. Braunwald, E., Goldblatt, A., Harrison, I). C‘.,
17.
18.
19.
20. 21.
22.
2.3.
and Masori. 1). I‘.: Srudie2. 011 c~n-tli~ tlirrlcn. sions in intact, unanesthetized n(an. Part I I I. Effects of muscular rscrcize. C'ircxlatiotl I thermodilution. J. Clin. Invest. 43:1015, 1964. Ring, R. J., Heimbeckcr, R., and Falholt, W.: i\n estimation of the residual volume of blood in the right ventricle of normal and diseased human hearts in yivo, AM. HEART J. 42:483, 1951. Holt, J. I’.: Estimation of the residual volume of the ventricle of the dog’s heart by two inclicator dilution technics, Circulation Res. 4:187, 1956. Schwarz, G. S.: 1)etermination of frontal plane area from the product of the long and short diameters of the cardiac silhouette, Radiology 47:360, 1916. Braunwald, E., Fishman, .1. E’., and Cournand, A.: Time relationships of dynamic events in the cardiac chambers, pulmonary artery and aorta in man, Circulation lies. 4:100, 1956. Folse, R., and Braunwald, E.: Determination of fraction of left ventricular volume ejected per beat and of ventricular end-diastolic and residual volumes. Experimental and clinical observations with a precordial dilution technic. Circulation 25:674, 1962. Gorlin, R., Rolett, E. L., Yurchak, I’. M., and Elliot, W. C.: Left \.entricular volume in mall measured by thermodilution, J. Clin. Invest. 43:1203, 1964. LVarner, H. Ii., and Toronto, A. F.: Effect of heart rate on aortic insufficiency as measured by a dye-dilution technique, Circulation Res. 9:413, 1961. Malooly, D. A., Dorrald, D. E., Marshall, H. LV., and Wood, E. H.: Combined flowmeterdye dilution study of the acute effects of changes in heart rate by vagal stimulation on the degree of experimental aortic regurgitation, Physiologist 4:70, 1961. Wilson, M. F.: Left ventricular diameter. posture, exercise, Circulation Res. 11:90, 1962. Mitchell, J. HI., Sproulc, B. J., and Chapman, C. B.: The physiological meaning of the maxin1n1 oxygelr int;rke test, J. Clin. Invest. 37:538, 1958. Linderholm. II.. and Strandell, T.: Heart volume in the prone and erect position in cer162:247, tain heart cases, .4 ctcl’ Med. Scandinav. 1958. Chapmall, c‘. B., Fisher, J. S.. :mtl Sproule, 13. J.: Bc+;lvior of stroke volurn~ at rest and
Volume 71 Number 3
Effects of supine exercise on L V volume in heart disease
during exercise in human beings, J. Clin. Invest. 39:1208, 1960. 24. Wang, Y., Marshall, R. J., and Shepherd, J. T.: The effect of changes in posture and of graded exercise on stroke volume in man, J. Clin. Invest. 39:1051, 1960. 2.5. Rushmer. R. F.: Postural effects on the base lines of ventricular performance, Circulation 20:897, 1959. 26. McGregor, M., Adam, W., and Sekelj, P.: Influence of posture on cardiac output and minute ventilation during exercise, Circulation Res. 9:1089, 1961. 27. Paley, H. W., Weissler, A. M., and Schoenfeld, C. D.: The effect of upright posture on left ventricular volume in man, (Abstract) Clin. Res. 12:10.5, 1964. 28. Linden, J. II.: Relation R. J., and Mitchell, between left ventricular diastolic pressure and myocardial segment length and observations on the contribution of atria1 systole, Circulation Res. 8:1092. 1960. 29. Braunwald, E., ‘Frye, R. L., Aygen, M. M., and Gilbert, J. W., Jr.: Studies on Starling’s law of the heart. III. Observations in patients with mitral stenosis and atria1 fibrillation on the relationships between left ventricular end-diastolic segment length, filling pressure and the characteristics of ventricular contraction, J. Clin. Invest. 39:1874, 1960. 30. Braunwald, E., Frye, R. L., and Ross, J. Jr.: Studies on Starling’s law of the heart. Determinants of the relationship between left ventricular end-diastolic pressure and circumference, Circulation Res. 8:12.54. 1960. 31. Buckley, N. M., Sidky, M., and Ogden, E.: Factors altering the filling of the isolated left ventricle of the dog heart. Effect of epinephrine and nonepinephrine, Circulation Res. 4:148, 1956. 32. Monroe, R. B., and French, G. N.: Left ven-
329
tricular pressure-volume relationships and myocardial oxygen consumption in the isolated heart, Circulation Res. 9:362, 1961. 33. Mitchell, J. H., Linden, R. J., and Sarnoff, S. J.: Influence of cardiac sympathetic and vagal nerve stimulation on the relation between left ventricular diastolic pressure and myocardial segment length, Circulation Res. 8:1100, 1960. 34. Sonnenblick, E. H., Siegel, J. H., and Sarnoff, S. I.: Ventricular distensibilitv and uressurevolume curve during sympathetic stimulation, Am. J. Physiol. 204:1, 1963. 35. Katz, A. M., Katz, L. N., and Williams, F. L.: Registration of left ventricular volume curves in the dog with the systemic circulation intact, Circulation Res. 3:588, 1955. E., Morrow, A. G., Cornell, W. P., 36. Braunwald, Aygen, M. M., and Hilbish, T. F.: Idiopathic hypertrophic subaortic stenosis, Am. J. Med. 29~924, 1960. 37. Wigle, E. D., Heimbecker, R. O., and Gunton, R. W.: Idiopathic ventricular septal hypertrophy causing muscular subaortic stenosis, Circulation 26:325, 1962. J. D., Farrehi, C., Klos38. Lewis, R. P., Bristow, ter, F. E., and Griswold, H. E.: Idiopathic left ventricular hypertrophy: A hemodynamic reappraisal, Am. J. Med. 38:842, 1965. 39. Dodge, H. T., Hay, R. E., and Sandler, H.: Pressure-volume characteristics of the diastolic left ventricle of man with heart disease, AM. HEART J. 64:503, 1962. 40. Braunwald, E., and Frahm, C. J.: Studies on Starling’s law of the heart. IV. Observations on the hemodynamic functions of the left atrium in man, Circulation 24:633, 1961. 41. Rapaport, E., Wong, M., Ferguson, R. E., Bernstein, P., and Wiegand, B. D.: Right ventricular volumes in patients with and without heart failure, Circulation 31531, 1965.
T
he effect of exercise on cardiac volume has interested investigators for many years. Several have studied the influence of exertion upon total heart volume in healthy subjects by radiographs, and the results have been variable for exercise both in the supine and sitting positions.‘-j Determination of total heart volume provides only an indirect estimate of individual chamber volume, however, and more complete understanding of the cardiac adaptation to exercise is aided by specific knowledge of changes in left ventricular size. Such measurements have become available from animal investigations in recent years. In the anesthetized dog, Chapman, Baker and Mitchell6 used an angiographic method and found a decrease in left ventricular end-diastolic and endsystolic volumes with electrically induced exercise. Rushmer, Smith and Franklin’ found decreases in left ventricular dimensions in the unanesthetized exercising dog, and also demonstrated that ventricular emptying was more complete during exercise. From the This study Received *Address: Ore.,
319
Division of Cardiology, Department was supported by United States for publication May 13, 1965. Department of Medicine, University 97201.
These effects of exercise in man have been the subject of two recent investigations. Changes in left ventricular dimensions with exertion were described by Braunwald and his associates.8 In 4 patients, silver clips were sewn to the left ventricle at the time of mitral commissurotomy or closure of an atria1 septal defect. After convalescence of the patients, cineradiographic analysis of the movement of the clips showed average decreases of 6.5 and 5.1 per cent, respectively, in left ventricular end-systolic and end-diastolic dimensions with exercise. Paley and Leonard9 studied left ventricular end-diastolic volume in 6 normal volunteers by the thermodilution method. With exercise which caused more than a twofold increase in the cardiac output, stroke volume rose but left ventricular end-diastolic volume did not change. In these patients, more complete emptying occurred from a left ventricle of unchanged diastolic size. The purpose of this report is to describe measurements of left ventricular volume
of Medicine, Public Health of Oregon
University of Oregon Medical Service Program Project Grant Medical
School,
3181
S.W.
School, Portland. No. HE 06336-03.
Sam Jackson
Park
Rd.,
Ore.
Portland,
changes with heart disease.
exercise
in 30 patients
with
REST
EXERCISE
Fs"/EDV:?O?~ EDV~235ml/M'
FS"IEDV 27% FDV:I59ml/M"
Method The thermodilution method for estimation of left ventricular volume has been described previously. lo*11 In this study the left ventricle was catheterized by the percutaneous transseptal method from the right femoral vein, and the left brachial artery was cannulated with polyethylene tubing. From the right femoral artery a retrograde catheter with a very small bead thermistor* at the tip was positioned just above the aortic valve. Determinations were made in all patients during a steady state at rest and during the fourth through sixth minutes of exercise. Seventeen patients pedaled a bicycle ergometer at a constant rate with the left leg, with resting measurements recorded after the foot was positioned on the pedal. The other 13 patients raised and lowered the left leg to a regular count, approximately 20 times per minute. Recordings were made of the electrocardiogram and left ventricular and brachial arterial pressures, and the cardiac output was measured by indocyaninegreen dilution. Oxygen consumption was determined in most patients by Scholander analysis of expired air. 1,lultiple thermodilution curves were produced by rapid injections of 5 ml., or rarely 10 ml., of cooled saline into the left ventricle. The changes in the temperature of aortic blood thereby produced were detected by the aortic thermistor (Fig. 1). By dividing the cardiac output by the heart rate, forward stroke volume (FSV) was determined. From the average downslope characteristics of the thermodilution curves, the ratio of FSV to ventricular end-diastolic volume (EDV) was obtained. Using FSV and this ratio (FSV/EDV), ventricular end-systolic volume (ES%‘) and the EDV were calculated.“J3 The formulas are :
(1) where tween *Victory
FSV/EDV
=
I-
y
Tn and Tn+l are differences bethe base-line temperature of aortic Engineermg
Corp..
Union,
N. J.
Fig. 1. Duplicate thermodilution curves at rest and during exercise in Patient 9. A decrease in the temperature of aortic blood is shown as an upward deflection. An average ratio of differences in temperature in the downslopes of the curves and a linowledge of stroke volume enabled us to calculate ventricular volume. In this patient who had aortic insufficiency the proportion of the end-diastolic volume ejected as the forward stroke volume averaged 20 per cent in three curves at rest and 27 per cent in three curves obtained during exercise. Enddiastolic volume decreased. FSV: Forward stroke volume. ED V: End-diastolic volume. The electrorardiogram is above.
blood and that found at beats n and n+l at end-diastole in the thermodilution curve
(3)
ESV
=
EDL‘
--
FSV
In the presence of aortic insufficiency the calculated ESV includes both the aortic regurgitant volume and the true ESV, because the indicator contained in the regurgitant volume contributes to the next end-diastolic ventricular concentration of indicator and is treated mathematically as though it had not left the ventricle in the preceding systole. Mitral insufficiency theoretically invalidates the method and no patients with this lesion were studied. The Teflon catheter employed for left ventricular catheterization is 70 cm. long, has four side holes located within 1.5 cm.
Volume Number
71 3
Efects
of supine exercise on L V volume in heart disease
of the tip, and is size 8MF. It was connected to a P23Gb strain gauge* by a 92-cm. length of nylon or Teflon tubing with a lumen diameter of 1.85 mm. Thirty patients with sinus rhythm were studied and the diagnoses in each are listed in Table I. The subjects presented a wide spectrum of severity of illness. Those with aortic valve prostheses and those who had undergone open commissurotomy for congenital aortic stenosis had few or no symptoms, whereas some with aortic valve disease were severely handicapped. No patient had evidence of retention of fluid at the time of the study, but congestive failure had been present previously in several. Three patients had clinical and angiocardiographic evidence of left ventricular hypertrophy without valvular disease. One of these had mild systemic arterial hypertension and a small systolic pressure gradient across the outflow tract of the left ventricle. The size of the cardiac silhouette in standard posteroanterior chest radiographs was determined by the method of Schwarz.14 This measurement provides a correction for body size and expresses frontal heart area as a percentage of predicted normal. Occasionally, the exact end-diastolic time for the measurement of pressure in the left ventricle was not apparent from inspection of the record, and the pressure 0.05 second after the onset of the QRS complex was used.15
The complete results are presented in Table I, and thermodilution curves from a patient are shown in Fig. 1. The results for voIume and flow were corrected for body size and expressed per square meter of body surface area (M.2). The presence of the tip of the transseptal catheter in the left ventricle during exercise did not produce important problems. In some cases, premature beats developed at the onset of exercise but disappeared when the catheter was moved slightly. Evaluation of the method. The frontal heart area from chest radiographs was compared with the EDV at rest (ml./M.2). The correlation coefficient was 0.75. One *Statham
Transducers.
patient with right ventricular enlargement due to an atria1 septal defect was excluded from this comparison. The reproducibility of the thermodilution curves was appraised in all patients during rest and exercise. At rest, 111 curves were obtained in the 30 patients, an average per patient of 3.7 curves. The downslope function (Tn + l/Tn) of each curve was compared to the average of downslope functions from all curves in that patient as follows: Average
downslope, in patient (Average
Inc.,
Hato
Rey.
Puerto
Rico.
all c”rves
downslope,
all curves
in patient)
At rest, the mean difference of individual curves from the average for the patient in whom they were obtained was 2.4 per cent without respect to sign (S.D. = 2.3 per cent). With exercise there were 107 curves, an average of 3.6 per patient. The mean difference of the downslope function for a given curve from the average for the patient was 3.5 per cent (S.D. = 3.4 per cent). The consistency of the exponential downslope of the individual curves was similarly analyzed. At rest, 387 pairs of downslope temperature “steps” were employed in the calculation of left ventricular volume, each curve providing an average of 3.5 pairs or ratios. The variation of each ratio from the average of downslope ratios for the curve was calculated : Average of downslope ratios for the curve
Results
321
(Average
> of downslope
_
Individual downslope ( ratio of the curve ratios for the curve)
>
X 100 = y. variation
At rest, the mean difference for a single downslope ratio from the averagg for the curve was 3.7 per cent, without +egard to sign (S.D. = 3.4 per cent). With exercise there were 401 downslope ratios, with an average of 3.8 per curve. The mean difference for any individual ratio from the average for the curve was 3.9 per cent, without respect to sign (SD. = 4.0 per cent). Marked changes from the ratio of FSV/EDV at rest did not often occur with exercise; two of the greatest were from 0.30 to 0.38 in one patient, and from 0.20 to 0.27 in another. Changes in the EDV were usually in the same direction as
322
Mristoz~‘, Kloster.
E;ctrrehi, Hroderrr,
Postoperative Aortic Valve Dise;lse 1. 45 1 100
L\‘H
I,ewz.s, llnd Griswold
Rest Eser. Rest Exer. Rest Exer. Rest Exer. Rest her.
2.
57
2
136
ST-T
.z.
51
1
110
L\‘H
4.
52
2
110
S’L’I
.5.
18
1
100
Normal
6.
13
1
101
LVH
Rest
7.
19
1
106
LVH
Excr. Rest Excr.
2
125
LVH
Aortic Insufficiency 8. 20 9.
51
2
150
L\TH
10.
19
2
165
L\:H
11.
41
2
130
LVH
12.
19
1
101
LVH
13.
54
2
136
L\‘H
14.
37
2
102
LVH
1.5.
32
1
136
L\!H
16.
42
2
135
17.
16
3
148
LI’H
18.
22
2
127
LVH
19.
42
2
156
IIBRB
20.
41
2
111
Normal
Rest Exel-. Rest Exer. Rest her. Rest Erer. Rest Exer. Rest Exer. Rest Ger. Rest EXN.
Aortic Stenosis and Insufficiency 21. 21 1 110
Rest Exer. Rest E:xcr. Rest Exer. Rest her. licst Eser.
L\W
Rest Exer.
Rest E:\er. IiCht t*:Wi-. Rest thei-.
22.
30
2
100
L\;H
23.
46
3
1.36
L\.H
24.
53
3
127
LVH
120 362 137 3.Z1 I i7 118 262 148 318 136 .%92. 152 .w 153 352 170 170 422 15’) 392 110 .15.5 35’, 154 318 1.57 271 1.54 296 148 170 3.13 I54 .ZhS 170 342 I 34
1-t’)
91 7x 9.3 71 8.5 76 96 83 107 68 140 108 120
2.28 2 7.5 3 02 3.79 3 70 .1.98 2 54 4.37 3.26 4.80 2.34 6.00 2.98 3 33
78 96 70 83 77 1ti 86 102 X8 100 68 9.z 68 90 70 114 68 84 81 90 87 120 78 102 92 108
3.71 3 95 3.27 3.54 4.35 5.99 2.62 3.18 2 77 2.99 1.95 3 22 2.80 .Z.lO 3.12 4.05 .z ,69 4.40 ,z 14 3.85 3.17 2.88 2.70 3.11 .Z.68* 5.12*
78 102 77 93 80 02 66 90
3 .99* 1.92* 3.02 4.19 1 49 2.12 1.88 2.45
if)
*Cal-disc output determined by the Fick principle. L1.U: Left ventricular hypertrophy. ST-T: Nonspecific S-7 segment and ‘T-wave abnormalities. KliHB: Right E.5’1’: End-systolic volume. CHF: Congestive heart failure. T’S: l’ricuspid stenosis. ..ll: .\ortic insufficiency. In the electrocardiogram, LVH was diagnosed when the R wave in Lead Va and the S wa\~ in Lead VI or Lead
bundle branch block. AS: Aortic stenosis. Vz totaled 35 mm. or
Volume Number
71 3
FSV (mlJM.2)
EDV (rd./M?)
ES V and regurgitant volume (ml./M.2)
Efects
of supine exercise on L V volume in heart disease
FSV gD>
-___-
Pressures (mm. Hg) Comments
Left
Central
ventrkle
aorta
30 30 39 41 52 47 33 46 39 45 34 43 28 28
100 88 130 108 100 85 106 164 115 122 87 113 165 140
70 58 91 67 48 38 73 118 76 77 53 70 137 112
.30 .34 .30 .38 .52 .55 .31 .28 .34 .37 .39 .38 .17 .20
128/a 176/7 150/13 192/l 7 125/s 182/18 125/3 170/4 127/10 130/5 120/25 150/22 148/10 160/10
48 41 47 43 56 51 30 31 31 30 29 35 41 34 43 36 54 52 39 39 36 24 35 31 40 47
218 172 235 159 373 268 176 163 163 150 181 167 186 155 187 190 186 179 216 216 180 171 206 206 108 104
170 131 188 116 317 217 146 132 132 120 152 132 145 121 144 154 132 127 177 177 144 147 171 175 68 57
.22 .24 .20 .27 15 :19 .17 .19 19 :20 .16 .21 .22 .22 .23 .19 .29 .29 .18 .18 .20 .14 17 :15 .37 .45
125/3 145/l 152/19 175/25 120/17 165/16 155/26 165125 125/13 150/10 175/17 215/21 130/14 160/16 118/6 175/18 135/l 1 170125 125/7 145/12 132/l 150/8 130/l 1 175/12 125/s 180/16
51 48 39 45 19 23 29 27
124 130 108 145 173 121 116 104
73 82 69 100 154 98 87 77
.41 .37 .36 .31 11 :19 .25 .26
180/12 190/15 144/7 168/6 170/44 160/36 230/31 280/34
LAD: ASD: more.
323
Left axis deviation with frontal QRS axis above Atria1 septal defect. with or without ST-T abnormalities.
minus
30 degrees.
Brachial artery
112/68 -
120/‘72 172/‘94 138i68 194196 95/50 162/80 110/70 145,‘88 142/80 165/85 lOS/SS 140/80 128/75 140,/88
S/SO 110/75 90/B 125/80
-
prosthesis
Aortic
prosthesis
Aortic
prosthesis
Aortic
prosthesis
Postoperative
AS, slight
AI
Postoperative
AS, slight
AI
Postoperative
.kS, slight
Al
145/60 185/85 165/45 CHF 185/60 168/45 Mean 132 142/73 1 so/so 140/70 170185 180/50 CHF 215/65 135/.55 ? CHF 185/65 138/55 200,BS lSOj60 .\nemia 175175 Mean 70 125/65 CHF 135/60 140/‘40 183/65 130/70 Slight 190,/90
155/50 125/45 132/78 120/75 170/50 130/60 118,‘60 150/60 1 lo/65 125/75 -
125/78 96/56 123/60
120/73 135/80 112/54 120/76 135/58 150/70 176/72 220196
156/68 -
FSV:
Aortic
Forward
stroke
TS,
volume.
in past
in past in past
(hematocrit
in past
AI
CHF
in past
CHF
in past
CHF
in past
EDV’:
28)
End-diastolic
volume. Conlinued.
7’able I .--- Cont’d.
I
I
I
I
Idiopathic 25.
Left 14
Ventricular 1
26.
41
2
100
LAr)
27.
41
2
111
LVH
5.5
2
130
RVH
29.
44
2
118
P mitrale
30.
20
2
10.)
Normal
Miscellaneous 28.
Hypertrophq 86
I LVH
changes in FSV. In the formula for EDV, it is apparent that this might be expected, since FSV is one of the components in the calculation of EDV. However, it is emphasized that the calculation of EDV depends both on FSV and FSV/EDV, and that these were independent measurements. There were examples in which EDV and FSV varied in opposite directions. Exercise in patients aff.er aortic valve surgery. In terms of physiologic handicap for the left ventricle, these 7 patients were the closest to normal of the entire group. Studies by indicator-dilution methods from several laboratories have shown the normal EDV at rest probably to be below 135 ml. per square meter,gJlJ6J7 and in only 1 patient in this group was this value exceeded at rest. In 4 patients the EDV fell 12 to 15 per cent with exercise, and the ESV also decreased. Changes in FSV were variable. In the other 3 patients, EDV rose with exercise, and definite increases in FSV were associated (15 to 39 per cent). Aortic insuficiency. There were 13 patients with aortic insufficiency of varying grades of severity, and in 12 of them the EDV at rest was distinctly abnormal. EDV decreased with exercise in 10 patients, although in only 4 was the change
I Rest Exer. Rest Exer. Rest Exer.
178 297 151 3.58 161 3 l,<
123 144 105 135 66 90
4.04 4.50 2.46 2.39 2.99 4.14
Rest Exer. Rest Exer. Rest Exer.
143
98 115 72 126 76 102
2.54 3.26 2.38 2 66 4 34 5 56
133 289 287
large. The average decrease was 13 per cent (range from 4 to 32 per cent). In of alteration of general, the direction FSV and of EDV was similar, but 3 patients had a rise in FSV associated with a smaller EDV. Three patients in this group had either no change or an insignificant change in the EDV. No patient in the group with aortic insufficiency developed a definite or large increase m EDV with exercise, despite the fact that some had severe disease. There was no apparent correlation between the clinical state of disability and the degree of response of the EDV to exercise. The methods employed do not provide a measure of total left ventricular stroke volume when aortic insufficiency is present, and thus the true ESV could not be determined in this group. Remaining grou$s. No consistent pattern was observed although there was a tendency for FSV and EDV to vary together. The most severely ill patient in the entire study had a decrease in EDV and a rise in FSV with exercise (Patient 23). The 3 patients with idiopathic left ventricular hypertrophy had a decrease in ES\’ and EDV with exercise.
Volume Nwmber
FSV (ml./M.2)
71 3
Efecb
ED V (mlJM.2)
ESV and regurgitant
volume (ml./M.2)
of supine exercise on L V volume in heart disease
325
(mm. Hg)
Pressures FSV
Comments
-EDV
Central
Left vent&e
Brachial artery
aorta
~
~
33 31 23 18 45 46
137 103 88 60 107 104
104 72 65 42 62 58
.24 .30 .26 .30 .42 .44
115/s 125/7 165/16 190/28 100/7 125/12
110/85 155/115 100/65 -
130/85 150/100 165/108 200/120 120/65 135/G
26 28 33 21 57 55
72 85 127 75 139 134
46 57 94 52 82 79
.36 .33 .26 .28 .41 .41
130/13 150/25 120/4 140/l lOO/ll 120/12
-
140/88 155/85 lZS/SO 160/98 115/65 135/80
End-diastolic volume-end-diastolic pressure relationships. There was no consistent relationship between end-diastolic pressure (EDP) and EDV when patients were compared at rest. Some had a definitely abnormal EDP with a normal EDV. Changes in EDV and EDP were most often in opposite directions during exercise. The most common pattern was a decrease in EDV associated with an increase in EDP during exertion. In only 9 of the 30 patients did EDV and EDP definitely change in the same direction. Discussion Changes in end-diastolic volume with exercise. From animal experiments and previous papers concerning exercise in man, we anticipated certain types of responses but did not consistently observe them. We expected that patients with gross cardiomegaly, abnormal EDP, and perhaps those with low cardiac output at rest would have further enlargement of the EDV with exercise, as has been suggested previ0us1y.~ Instead, we often found decreases in EDV with exercise in those with the largest ventricles at rest. Only limited generalization from this point is possible because all those in the present study with
110/70 -
Systemic hypertension
Secundum ASD Mitral
stenosis
Mild mitral stenosis
the most severe diseasehad some degree of aortic insufficiency. It is possible that tachycardia and perhaps other factors result in a decrease in the proportion of the stroke volume which regurgitates during exercise, and a smaller EDV might occur.18Jg This explanation is suggested in 7 of the patients with aortic insufficiency who had an increase in FSV/EDV with exercise. The fact remains, however, that EDV decreased with exercise in patients with severe heart disease due to aortic insufficiency, some of whom had had congestive heart failure. With important aortic insufficiency, the ratio FSV/EDV is low, and minor variations or errors in the measurement will produce relatively large changes in the calculated EDV, for a given FSV (see Formula 2). However, this factor is not believed to be the explanation of the changes in the aforementioned patients, since multiple thermodilution curves were analyzed in each patient, because the changes in EDV were reasonably consistent in the aortic insufficiency group, and because the major changes with exercise were of FSV in some patients rather than of FSV/EDV. In view of past work we anticipated that the postoperative patients without
a gross handicap for the ventricle would have either a decrease in El)\. \vith exercise or no change. Those who had a smaller ESV and ED\,’ with the same or larger FS\’ lvith exercise demonstrated this expected normal response with more cotnplete emptying. However, the findings in 3 other patients in the postoperative group and 2 other patients (Patients 22 and 28) suggest that the abnormal heart \vith a normal EDV at rest ma\: show an increase in the EI>V with exercise. If this is the case, a higher FSV will very likely be associated. Whether this response is abnormal is not knobvn, since no patients in the present study could be considered to be entirely free of heart disease. Other studies of cardiac performance suggest that a larger ED\: with exercise need not be abnortnal. Occasional increases in left ventricular diameter in the dog during exertion \vere described by Wilson.?” It also has been shown that FSV may rise remarkably during exercise in healthy people, and it is possible that a normal increase in the proportion of ventricular emptying might not be sufficient to account for the degree of rise observed in FS\;. Thus, an increase in EDV would be required. For example, in studies of healthy subjects \vho exercised in the upright: posture to the tnaximunt possible oxygen consumption, _\Iitchell, Sproule and Chapntan2t found that the average FSV doubled. If the normal left ventricle at rest were 40 to 60 per cent emptied by each systole, which is a reasonable estimate, an increase in EDV would surely be necessary to provide a twofold increase in stroke volume, even if ventricular emptying were remarkably complete with exercise. The more complete the etnptying at rest, the more likely that EDV would increase with exeriise, if FSV were to increase greatly. This observation is not entirely analogous to our study, hobyever. Our patients \vere in the supine position, and the decreases in heart volutne and FSV known to occur with assumption of the erect posture provide a different base line for comparison.22-27 Furthermore, in our patients who had an increased EI>\jT with exercise the increase in FSV was not of such great magnitude. Finally, the level of exercise in our stud>,
~;ts consideral)I~- short of t tw nt;txintulll ox\.gen cotisuittption. For t lw present I ttoivever, \v~ I~;ive concluded that ;L normal resting left ventricular I:I)\’ \vhich ittcreases \\.itlt exercise ttt;t>’ not consti tutc abnormal response, \\ hen significant at1 increases in F’S\’ ;trc’ :tssociated. When consideration is given to the several factors \vhich could influence left ventricular votuttte, it perhaps is not too surprising th;tt the values found were not more often predictable. These influences might include right ventricular performance, the volume and pressure of the filling reservoir for the tcft heart, inotropic effects on left ventricular performance, and the impedance to left ventricular outflow. linti tnore exact nteitns are available for accurateI>- quantifying contractile force of the left ventricle in intact patients. the relative intportancc of any one of these influences tnay remain uncertain. EDP-EDI- relationships. The lack OS a consistent relationship between left ventricular El)l’ and EI)j‘ is of theoretical interest and practical importance. I’ublished nork clearly relates the end-diastolic length of a vent&ular ntuscle segment to EI)I’ in a consistent manner in the dog.“” In addition, the relationship between the length of ;I segment of left ventricular muscle and El)1 is ;i predictable one, Lvhen studied at the titrte of thoracotom>~ in patients with mitral stenosis and atria1 fibrillation.‘!’ \‘entricular muscle segmettt length varies in the same direction with ED\‘, and therefore a consistent relationship was expected between El)\- and El)I’. ‘This did not always obtain in our patients during exercise. When EI)T’ and EI)V changed itt the Sante direction, our observations were consistent \vitlt published experimental data. ttt most instances, however, EI>I’ and EDI7 moved in opposite directions, contrary to the concept of a consistent pressure-volume curve for the left ventricle at end-diastole. Several aspects of the exercise response were considered in searching for an explanation. Alarked tachycardia increases the intpedance to ventricular filling in the experimental anitnal, perhaps because of incomplete ntuscular relaxation.3’1-a:i ‘l’achg;cardia has also been ioutd to have thw effect in the humatt hwrt, but ottl>, with
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very short diastolic periods, when studied at the time of surgery in patients with mitral stenosis.2g However, the changes in heart rate in our patients were not extreme, and we are forced to conclude that the effects of heart rate alone on the ventricle in diastole do not explain the changes observed. The effects of sympathetic nervous system activity or circulating catecholamines have been reported variously to decrease impedance to ventricular filling,31 not to change diastolic pressure-volume (or muscle segment length) relationships,32-34 and to increase diastolic left ventricular impedance.35 In view of these reported variations, it is not possible to conclude with certainty what effects would be expected from these influences in our patients with abnormal hearts. There have been reports in recent years suggesting that the physical properties of the ventricle are altered by left ventricular hypertrophy. The outstanding example is idiopathic hypertrophic subaortic stenosis, in which the left ventricular cavity volume is small, the wall is thick, and left ventricular EDP is often elevated. From such findings it has been concluded that the diastolic compliance of the ventricle is reduced, resulting in a higher EDP for a given EDV. 36-38The concept of low ventricular compliance helps to explain the lack of correlation of EDP and EDV values obtained in patients at rest. However, if alterations in compliance alone were involved, then consonant changes along this new pressure-volume curve with exercise would still occur, and this wTe seldom observed. However, the compliance characteristics (elastic factors) of the ventricle are not the only determinants of diastolic ventricular pressure, as Dodge39 has pointed out. The resistance components (viscous factors of blood and ventricular wall) are usually overlooked in view of the geometry of the ventricle, the short distance ventricular blood travels in diastole, and the large ratio of volume to surface area of the chamber. But the resistance component of ventricular muscle determinant of may be an important EDP in some patients, since its effect is proportional to the rate of change in diastolic ventricular volume. It could be
327
postulated that changes in ventricular compliance are associated with forceful atria1 contraction when left ventricular hypertrophy is present,4O and that an accelerated rate of contraction by the left atrium during exercise magnifies the effects of the viscous resistance to left ventricular distention, a rate-dependent function. This influence which increases EDP could overshadow the opposite effect on pressure of a smaller volume and thereby produce the results that we found in many patients, a smaller EDV and a higher EDP. Other factors are undoubtedly of importance also. It is recognized that the left ventricular pressures that we measured were not the transmural or effective distending pressures, since no intrapericardial or intrapleural reference pressure was available. It does not seem to us to be likely that changes in intrapleural pressure could account for all of the variability of the changes in EDV-EDP relationships, but such changes represent an unpredictable, perhaps important factor. Alterations in intrapericardial pressure would be especially important if changes in volume of other intrapericardial chambers occurred and the pericardium were not distensible. Work by Rapaport and associates4r is of considerable interest in this regard. They measured right ventricular volumes by thermodilution in patients with heart failure. In five of six instances, right ventricular EDV rose with exercise. Intrapericardial pressure could be altered by such changes, thereby altering the measured or absolute left ventricular diastolic pressure in an unpredictable manner. Regardless of the factors responsible, we believe that it is evident from our results that the EDV (or muscle fiber length) could not be consistently predicted from the EDP at rest or with exercise in our patients. Furthermore, the ability of the abnormal left ventricle to change its EDV in a given direction could not be determined from the EDP. Thus, we believe that EDP, as routinely measured during cardiac catheterization in man, cannot be used alone as an assessment of the adequacy of the cardiovascular response to exertion by the abnormal heart. It also follows that changes in left atria1 pressure or pulmonary capil-
lary pressure are not consistently valid reflections of changes in left ventricular EDV. Summary Left ventricular end-diastolic volume (EDV) was measured by thermodilution in 30 patients with heart disease. Those with little physiologic abnormality varied in their response to exertion. In some, EDV decreased while forward stroke volume (FSV) was maintained or increased. In others, EDV and FSV rose during exercise. Patients with aortic insufficiency usuall) had a decrease in EDV with exercise, whether FSV increased or decreased. In patients with other lesions, FSV and ED\‘7 tended to vary together. Changes in EDV and left ventricular end-diastolic pressure with exercise were usually not in the same direction, and the factors which may explain this unexpected finding are discussed. It is concluded that end-diastolic pressure, as usually measured in the left ventricle during cardiac catheterization, will not reliably describe EI)\: or its changes with exercise. We helpful
are indebted discussions
to Dr. Benjamin during preparation
Ross for his of this paper.
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REFERENCES 1.
2.
\3
4.
5.
6.
7.
8.
Meek, W. J., and Eyster, J. A. E.: Cardiac size and output in man during rest and moderate exercise, Am. J. Physiol. 63:400, 1923. Liljestrand, G., Lysholm, E., and Nylin, G.: The immediate effects of muscular work on the stroke and heart volume in man, Skandinav. Arch. Physiol. 80:265, 1938. Kjellberg, S. R., Rudhe, U., and SjGstrand, ‘I‘.: The amount of hemoglobin (blood volume) in relation to the pulse rate and heart volume during work, Acta Physiol. Scandinav. 19:152, 1949. Ruosteenoja, R., Linko, E., Lind, J., and Sollberger, A.: Heart volume changes at rest and during exercise, Acta Med. Scandinav. 162:263, 1958. Holmgren, A., and Ovenfors, C. 0.: Heart volume at rest and during muscular work in the supine and sitting position, Acta Med. Scandinav. 167:267, 1960. Chapman, C. B., Baker, O., and Mitchell, J. H.: Left ventricular function at rest and during exercise, J. Clin. Invest. 38:1202, 1959. Rushmer, R. F., Smith, O., and Franklin, D.: Mechanisms of cardiac control in esercisr, Circulation Res. 7:602, 1959. Braunwald, E., Goldblatt, A., Harrison, I). C‘.,
17.
18.
19.
20. 21.
22.
2.3.
and Masori. 1). I‘.: Srudie2. 011 c~n-tli~ tlirrlcn. sions in intact, unanesthetized n(an. Part I I I. Effects of muscular rscrcize. C'ircxlatiotl I
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during exercise in human beings, J. Clin. Invest. 39:1208, 1960. 24. Wang, Y., Marshall, R. J., and Shepherd, J. T.: The effect of changes in posture and of graded exercise on stroke volume in man, J. Clin. Invest. 39:1051, 1960. 2.5. Rushmer. R. F.: Postural effects on the base lines of ventricular performance, Circulation 20:897, 1959. 26. McGregor, M., Adam, W., and Sekelj, P.: Influence of posture on cardiac output and minute ventilation during exercise, Circulation Res. 9:1089, 1961. 27. Paley, H. W., Weissler, A. M., and Schoenfeld, C. D.: The effect of upright posture on left ventricular volume in man, (Abstract) Clin. Res. 12:10.5, 1964. 28. Linden, J. II.: Relation R. J., and Mitchell, between left ventricular diastolic pressure and myocardial segment length and observations on the contribution of atria1 systole, Circulation Res. 8:1092. 1960. 29. Braunwald, E., ‘Frye, R. L., Aygen, M. M., and Gilbert, J. W., Jr.: Studies on Starling’s law of the heart. III. Observations in patients with mitral stenosis and atria1 fibrillation on the relationships between left ventricular end-diastolic segment length, filling pressure and the characteristics of ventricular contraction, J. Clin. Invest. 39:1874, 1960. 30. Braunwald, E., Frye, R. L., and Ross, J. Jr.: Studies on Starling’s law of the heart. Determinants of the relationship between left ventricular end-diastolic pressure and circumference, Circulation Res. 8:12.54. 1960. 31. Buckley, N. M., Sidky, M., and Ogden, E.: Factors altering the filling of the isolated left ventricle of the dog heart. Effect of epinephrine and nonepinephrine, Circulation Res. 4:148, 1956. 32. Monroe, R. B., and French, G. N.: Left ven-
329
tricular pressure-volume relationships and myocardial oxygen consumption in the isolated heart, Circulation Res. 9:362, 1961. 33. Mitchell, J. H., Linden, R. J., and Sarnoff, S. J.: Influence of cardiac sympathetic and vagal nerve stimulation on the relation between left ventricular diastolic pressure and myocardial segment length, Circulation Res. 8:1100, 1960. 34. Sonnenblick, E. H., Siegel, J. H., and Sarnoff, S. I.: Ventricular distensibilitv and uressurevolume curve during sympathetic stimulation, Am. J. Physiol. 204:1, 1963. 35. Katz, A. M., Katz, L. N., and Williams, F. L.: Registration of left ventricular volume curves in the dog with the systemic circulation intact, Circulation Res. 3:588, 1955. E., Morrow, A. G., Cornell, W. P., 36. Braunwald, Aygen, M. M., and Hilbish, T. F.: Idiopathic hypertrophic subaortic stenosis, Am. J. Med. 29~924, 1960. 37. Wigle, E. D., Heimbecker, R. O., and Gunton, R. W.: Idiopathic ventricular septal hypertrophy causing muscular subaortic stenosis, Circulation 26:325, 1962. J. D., Farrehi, C., Klos38. Lewis, R. P., Bristow, ter, F. E., and Griswold, H. E.: Idiopathic left ventricular hypertrophy: A hemodynamic reappraisal, Am. J. Med. 38:842, 1965. 39. Dodge, H. T., Hay, R. E., and Sandler, H.: Pressure-volume characteristics of the diastolic left ventricle of man with heart disease, AM. HEART J. 64:503, 1962. 40. Braunwald, E., and Frahm, C. J.: Studies on Starling’s law of the heart. IV. Observations on the hemodynamic functions of the left atrium in man, Circulation 24:633, 1961. 41. Rapaport, E., Wong, M., Ferguson, R. E., Bernstein, P., and Wiegand, B. D.: Right ventricular volumes in patients with and without heart failure, Circulation 31531, 1965.