Noninvasive Measurement of Cardiac Function during Exercise, Using Resaturation Curves

Noninvasive Measurement of Cardiac Function during Exercise, Using Resaturation Curves* Lucy S. Goodenday, M.D.;• • Brian Ayotte, M.D.;t Erik S. Carlsson, M.D.;; and Malcolm B. Mcilroy, M.D.§

1be reataratioD curve, a noninvasive indicator-dilution test using an ear oldmeter to detect rates of change in arterial oxygen saturation during breathing of various concentrations of oxygen, was used to assess cardiac perfonnance in normal subjects and in 108 patients with cardJac: valvular disease. Measurements made during exercise indnded the time constant of resaturation (T) and beat-to-beat changes in arterial oxygen saturation (the left heart clearance fraction). At maldmum rates of voluntary work, patients bad a significantly reduced clear-

ance fraction and longer T than normal subjects. Clearance fraction and T improved in patients after aortic valve replacement; deterioration occurred in T and clearance fraction over time in patients treated medically, as compared to normal subjects who showed UUie change during a ten-year period. Cleanmce fraction and T correlated with hemodynamic data obtained during cardiac catheterization. 1be resaturation curve provides an objective measure of cardiac impairment that can be readUy repeated during foUow-up of patients with heart disease.

testing has become a routine procedure in Exercise most cardiac laboratories; however, the reliabil-

become a routine part of the clinical evaluation of patients in this laboratory. A total of 158 studies have been performed in 108 patients with cardiac valve disease, and serial studies at intervals up to ten years have been performed in seven normal subjects and in 22 patients with clinically unchanged heart disease. We describe here the results obtained with this test and demonstrate its usefulness in long-term follow-up of patients with cardiac disease.

ity of the information gained from such tests varies with the motivation of the patient to continue and with the familiarity of the patient with the test. 1 There is frequently a need for an objective, noninvasive, readily repeatable test that will measure not only the patient's disability (which may be what he will or won't do rather than what he can do), but also the degree of cardiac impainnent. The resaturation curve, a noninvasive index of cardiac function and a variation of indicator-dilution curves,2 was first described in 1966.3 It was then shown to give objective and repeatable values during exercise. In more than 1,000 tests in patients with various cardiac disorders since that time, the resaturation curve has proved completely safe; it has •From the Cardiovascular Research Institute and the Departments of Medicine and Radiology, University of California, San Francisco, and the Veterans Administration Hospital, San Francisco. This study was supported in part by National Institutes oE Health grants HL-06285 and 5Tl2-05740-01. ••Fonner Assistant Clinical Professor of Medicine and Chief, Cardiac Clinic, Veterans Administration Hospital; presently Assistant Professor of Medicine, University of Michigan School of Medicine, and Chief, Cardiology Division, Veterans Administration Hospital, Ann Arbor, Mich. tFormer Cardiac Resident, Cardiovascular Research Institute· presently Associate Professor of Medicine, School of Medicine, University of Manitoba, St. Boniface, Manitoba. iProfessor of Radiology. §Professor of Medicine. Manuscript received August 14, 1975; revision accepted May 18. Reprint requests: Editorial Desk, 1315 Muffrtt Hospital, Cardiooa8cular Research Institute, University of California, San Francisco 94143

732 GOODENDAY ET AL

MATERIALS AND METIIODS

The Clinical Test An ear oximeter (Waters-Conley XEOOA) was used in most studies. In some later studies another oximeter (Waters 0-500) was employed. Other necessary equipment included that found in most pulmonary function laboratories: a cycle ergometer, a breathing valve, and a physiologic recorder with an electrocardiograph and DC amplifiers. The respiratory valve must have a stopcock enabling the investigator to switch inspired gas from room air to low concentrations of oxygen and to 100 percent oxygen. Monitoring of the oxygen pressure or nitrogen pressure at the mouthpiece is helpful to remind the physician not to leave the patient breathing a gas mixture low in oxygen content. Although we measured oxygen consumption to check the work rate indicated by the cycle ergometer, this is not necessary if a calibrated ergometer is employed. Resaturation curves3 are recorded during a standard exercise test.4 The subject exercises on a cycle ergometer for a fixed period (usually six minutes) at a fixed workload while breathing room air. A short period of mild hypoxia is then induced by having the subject breathe a gas mixture low in oxygen content for one to three breaths; the intent is to bring the alveolar oxygen tension ( P A02) to between 50 and 60

CHEST, 70: 6, DECEMBER, 1976

5 Hconds

ECG

ARTERIAL~ OXYGEN

SATU~ATION

FIGURE

1. Resaturation curves obtained in a normal subject during moderate exercise.

mm Hg for five to ten seconds. The patient then breathes 100 percent oxygen, which abruptly raises the PA02 to about 350 mm Hg and causes effectively instantaneous resaturation of hemoglobin in the blood in the pulmonary capillaries. The changes in arterial oxygen saturation ( Sa02) that result from the changes in inspired oxygen tension are recorded with an ear oximeter. The sequence is repeated at higher workloads until the patient's tolerance is reached. Analysis of the Test

Analysis of resaturation curves involves measuring the time required for Sa~ to rise 63 percent of the distance to its final equilibrium value from an arbitrary initial starting point. This is the time constant ( r) of resaturation ( indicator clearance). A sample curve is shown in Figure 1, in which r is indicated. Like other indicator-dilution curves, the resaturation curve (in which reduced hemoglobin is the indicator) may be replotted on semilogarithmic paper, and a straight line may

be drawn through the points. The equation describing the curve is (1)

where C is the concentration of reduced hemoglobin in arbitrary units, Co is the initial concentration, t is the elapsed time in seconds, e is the base of the natural logarithm, and r is the time constant of the curve. r equals V/Q where V is the volume of the dominant mixing chamber between injection and sampling sites and Q is the cardiac output.li Q is the product of stroke volume and heart rate, and r can be expressed as follows : r

= V/Q = SV

v

(2)

X HR

where SV equals stroke volume and HR equals heart rate. Rearranging this equation, a dimensionless ratio, SV/V, can be calculatied: SV= 1 (3) V rXHR

Table 1--Compari.on of Reaaturarion Time Corutant (r) and Cleararu:e FrGt:rion at Similar Work Rate. in Normal Subject• and Patient. aoith CartliGt: J'al11e IJiNae • r , seconds

Work Rate (Vo., ml/min)

Normal Subjects (No.)

Patients with aortic valvular disease 279 ± 74 514 ±59 719 ±56 912 ± 60 1,101 ± 52 1,274 ± 58

3.9 2.2 1.9 1.7 1.6 1.4

Patients with mitral stenosis 734 ± 219t

1.9 ± 0.7 (20)

± 0.9 ± 0.3 ± 0.7 ± 0.5 ± 0.5 ± 0.4

(31) (20) (20) (20) (20) (20)

Clearance Fraction, percent

Patients (No.)

p <**

Normal Subjects (No.)

± 1.4 ± 1.3 ± 1.3 ± 0.9 ± 0.9 ± 0.6

(45) (25) (31) (32) (11) (16)

0.010 0.005 0.005 0.005 0.025 0.005

21 ± 26 ± 29± 30 ± 30 ± 32 ±

2.6 ± 0.5 (50)

0.005

29 ± 10 (20)

4.6 4.1 3.2 2.8 2.2 2.0

6 8 7 10 13 12

(31) (20) (31) (20} (20) (20)

Patients (No.)

p <**

6 7 7 8 10 8

(45) (25) (31) (32) (11) (16)

0.005 0.005• 0.005 0.005 0.050 0.010

17 ± 6 (50)

0.005

15 ± 16 ± 20± 20± 21 ± 23 ±

*Table values are means ± SD. ••Group mean t-test. tHighest work rate attained by patients with mitral stenosis. Values for normal subjects were obtained at work rate of 719 ± 56 ml/min.

CHEST, 70: 6, DECEMBER, 1976

NONINVASIVE MEASUREMENT OF CARDIAC FUNCTION 733

Table 2--Re.aturation Time Coru~ana ( r) and Clearance Fraetion in Normal Subject• Studied al Se~~en-Year or Ten-Year lnlert!GU Age at Time of Study, yr

Subject, Sex

Body Surface Area, sq m

Oxygen Uptake, ml/min

Heart Rate, beats per minute

seconds

Clearance Fraction, percent

T,

1, F

26 33

1.48

1,163 1,380

146 170

1.7 1.3

24 27

2,M

31 41

2.00

2,013 1,940

168 160

1.5 1.3

24 29

32

1.80

1,940 1,596

160 170

1.6 1.2

24 29

3, M

42

4, F

34 41

1.74

1,731 1,910

153 150

1.8 1.8

22 22

5,M

39 49

1.80

2,160 2,270

168 144

1.4 2.8

25 15

6, F

40 47

1.70

1,250 1,450

148 174

1.0 1.4

40 25

7,M

42 50

2.20

2,600 2,130

180 140

1.3 1.7

26 25

Mean change

± SE

8

-26 ± 106

± 0.6

The value, SV IV, has been called the left heart indicator clearance fraction; and this, plus the value r, are the measurements from the resaturation curve reported in this study. r depends on heart rate and decreases with increasing cardiac output, whereas the clearance fraction decreases with impairment of cardiac function, either because stroke volume falls or because left heart volume increases. V alidotion of the Method

Oximeters were calibrated with filters until a method for individual calibration against PA02 was devised.6 The linearity of the instrument was checked by calibration against samples of arterial blood. The response of the XE60A oximeter to changes in Sa02 gave the best 6t with a plot of the deBection of the oximeter against the logarithm of the percentage of reduced hemoglobin. The response of the 0-500 oximeter was linear. The relationship of left heart clearance fraction to left ventricular ejection fraction was documented by recording resaturation curves at the time of left ventricular biplane cineangiographic studies in 19 patients; there was signi6cant correlation between the measurements ( r 0.81) .7 The relationship of resaturation curves to overall cardiac function was tested by comparing r and the clearance fraction, recorded at the highest work rate achieved by the patients, with other measurements obtained during the regular clinical evaluation of the patients. Variables used for this comparison included classification of disability,S degree of left ventricular hypertrophy,D cardiac volume,lO and intravascular pressures, flows, and cineangiographic data available for 91 patients. Reproducibility of resaturation curves was confumed by comparing studies in normal subjects and patients with clinically unchanged heart disease performed at intervals up to ten years.

=

REsULTS

At all levels of oxygen consumption, patients had significantly longer average values for T and smaller

734 GOODENDAY ET Al.

-2

±9

0.2

± 0.2

-2

±3

values for the clearance fraction than those found in normal subjects (Table 1). The results of studies performed several years apart in normal subjects exercising at a moderate work rate are shown in Table 2. Differences in calibration of the cycle ergometers used in the studies resulted in differences in oxygen consumption in several subjects. There were no consistent differences in T or the clearance fraction between the two studies in an individual subject at a given work rate. T tended to increase in the fifth decade of life, but only in subject 5 was the difference in T on serial studies greater than 0.4 seconds; this difference may be accounted for by the difference in heart rate on the two occasions, The clearance fraction was less constant but varied by more than 5 percentage points in only two of seven normal subjects. In the 22 patients with stable heart disease shown in Table 3, the average differences between test 1 and test 2 were also small, with the standard deviations of the differences being 18 percent for T and 11 percent for the clearance fraction. In contrast to normal subjects, cardiac function estimated by resaturation curves tended to deteriorate with time in patients with cardiac valve disease, and findings generally paralleled the clinical assessment. Representative patients are described in Table 4. Nevertheless, if the clinical course was altered by therapy (such as cardiac surgery or treatment with digitalis), cardiac function improved (patients 1, 3, 4, and 9 in Table 4, for example). Mean ages of normal subjects and patients studied serially were similar at the time of the latest studies;

CHEST, 70: 6, DECEMBER, 1976

Table 3-&rial Studiu in Parienl• with Clinically Stable Heart D i Age (yr),

Sex

Interval Between Tests, mo

Body Surface Area, sq m

V«>t, ml/min

Heart Rate, beats per minute

seconds

Clearance Fraction, percent

T,

48, F

2

1.7 1.7

663 574

102 102

1.1 1.1

49 49

37, F

3

1.8 1.7

1,210 1,240

140 159

2.3 1.9

19 20

25, F

6

1.9 1.5

738 730

123 141

1.5 1.2

32 35

68,M

6

1.8 1.9

945 880

94 88

3.1 2.2

29 32

49, M

57

2.1 2.1

1,100 925

96 110

1.6 1.6

39 34

32, M

10

1.9 1.9

2,420 2,580

150 145

1.3 1.1

29 31

36, F

24

1.9 1.9

848 1,120

122 130

2.3 1.9

21 21

72, M

15

1.8 1.7

740 550

92 83

1.8 2.1

32 30

53, F

6

1.8 1.8

605 676

123 117

1.6 1.3

28 33

42, F

43

1.8 1.6

1,139 1,010

162 142

1.4 1.6

26 26

45, M

41

1.9 1.9

1,030

108 118

2.4 2.6

23 18

2.0 2.0

1,530 1,210

108 110

1.9 1.8

28

1.9 2.0

2,010 1,530

117 110

1.6 1.8

28

23, M

5

23, M

8

25 24

23, M

12

1.9 2.0

1,425 1,530

115 110

1.6 1.8

29 28

55, M

56

2.2 2.0

1,320 1,047

90 102

4.6 5.1

14 12

55, F

6

1.5 1.5

360 442

114 100

1.3 1.9

31

2.0 2.0

994 896

114 96

2.9 3.4

18 18

1.9 1.9

814 900

131 134

2.1 1.7

19 24

45, M

15

39, M

28

51, M

33

2.0 2.0

875 1,230

78 90

3.4 3.3

23 20

29, F

12

1.3 1.3

598 588

156 156

1.8 1.7

21 23

39, F

12

1.7 1.6

585 750

152 144

1.6 1.3

28

1.9 1.9

1,700 1,730

125 125

1.3 1.0

33 36

±

o ± 11•

32, F Mean difference ± SD

3 17

±

17

+0.04

± 0.11•

+23

198*

0.05

± 0.36*

32

-0.6

± 3*

*Not significant.

CHEST, 70: 6, DECEMBER, 1976

NONINVASIVE MEASUREMENT OF CARDIAC FUNCTION 735

Table 4--Serial Seudie• of Rumuration Time Con.lanl ( T) and Clearanee Fraction in Patient. Exercise Study Age at Patient, Time of Diagnosis* Study,yr 1,MS

Cardiac Volume, ml

34 36

655

42

2,MS

52 57

3,AVD

23

653

Oxygen Uptake, ml/min

4.9 4.2

682 688

1.7 2.4

33 23

106 110

5.4

792

1.3

31

148

3.9 2.9

704 740

2.4 2.7

17 16

150 140

NYHA class 2; mitral valvotomy Still class 2; no improvement in symptoms or wedge pressure

1,301

3.2

12

162

1,100

1.6

24

156

1,180

1.6

26

144

Asymptomatic, but ressturstion curves show abnormally slow x and small clearance fraction Onset of severe clinical heart failure ; mitral regurgitation now present; sortie and mitral valves replaced Much improved; rhythm is atrial fibrillation Normal sinus rhythm

3.5

25

26

Cardiac Output, L/min**

1,360

26

T,

seconds

Clearance Heart Rate, Fraction, bests per percent minute

1,105

Clinical Commentst

NYHA class 2 Cardiac function impaired; mitral valvotomy performed; slight symptomatic improvement Some findings improved, but wedge pressure and calculated mitral valvular ares not improved

4,AVD

27 29

1,296

5.6

730 1,550

4.0 2.1

14 22

108 132

NYHA cl888 2 ; sortie valve replaced Asymptomatic

5,AVD

36 37

1,235 1,682

5.6 4.9

757 1,380

2.6 3.2

21 15

108 126

38

1,302

815

1.7

29

120

NYHA cl888 2 NYHA cl888 3; findings show increasing cardiac impairment; sortie valve replaced NYHA class 2

6, AVD

23 30

840 850

1,510 1,313

2.0 1.9

30 24

99 132

Asymptomatic Asymptomatic; findings remain within normal limits, but clearance fraction has decreased slightly (possible early cardiac decompensation)

7, MS

31

612

3.2

15

126

31

549

2.7

19

120

Atrial fibrillation; sinus rhythm restored Sinus rhythm

3, ACD

59 59

632 935

3.0 1.8

12 29

167 114

Atrial fibrillation Sinus rhythm

9,AVD

23

780

2.5

21

114

770

1.4

34

126

Dyspnea on extreme exertion; digitalization Asymptomatic with digitalis therapy

25

7.4

4.5

*MS, Mitral stenosis; AVD, sortie valve disease; and ACD, arteriosclerotic cardiovascular disease. ••Cardiac output at catheterization (supine rest) . tNYHA, New York Heart Association.

the mean age of normal subjects was 43 years, the mean age of patients with mitral stenosis was 41 years, and the mean age of patients with aortic valve disease was 41 years. The clearance fraction and T were cross-correlated 11 with other measurements of cardiac function. In 50 patients with mitral stenosis, the clearance fraction and T correlated significantly with many

738 GOODENDAY ET AL

other independent variables, some of which are displayed in Table 5. The clearance fraction correlated significantly with more variables than any other single measurement of cardiac function, including pulmonary wedge pressure. Age, disability, heart volume, pulmonary wedge pressure, pulmonary vascular resistance, and mitral valve area were all significantly related to the clearance fraction. The heCHEST, 70: 6, DECEMBER, 1976

Table ~orrelation Coef/kienu (r) of Re.aturation Time Corutant ( T) and Clearan.ee Fraetion in Patient•

Clearance Fraction,

T

,..-----"-----

Group and Measurement

T, seconds r p <

Mitral stenosis (50 patients) Heart volume 0.49 Mean wedge pressure 0.42 Mitral valvular area• -0.41 Total pulmonary resistance 0.37 Aortic valve disease (58 patients) Dyspnea on exertion 0.38 Heart volume 0.49 Angiographic severity of aortic regurgitation 0.31 Left ventricular enddiastolic pressure 0.47

~

percent p

r

<

0.001 0.005 0.01 0.025

-0.45 -0.50 0.62 -0.51

0.005 0.001

-0.29 0.05 -0.60 0.001

0.05

-0.30 0.05

0.001

-0.43 0.005

0.005 0.001 0.001 0.001

•calculated according to formula of Gorlin and Gorlin.' 2

modynamic measurement that correlated significantly with most other independent variables was the calculated mitral valve area; if the valve area was

small, the heart volume tended to be large, the clearance fraction small, and T increased. In the 58 patients with aortic valve disease, T correlated significantly with more independent variables than any other single measurement, some of which are shown in Table 5. The closest relationship in these patients was found between the clearance fraction and heart volume (inverse correlation). Both T and the clearance fraction were significantly related to left ventricular end-diastolic pressure in the expected manner. T also demonstrated a poor but valid correlation with the severity of left ventricular hypertrophy, with the degree of aortic regurgitation on angiographic studies, and inversely with the supine cardiac output measured during cardiac catheterization. Results in ten patients studied during atrial fibrillation and again after restoration of sinus rhythm are shown in Table 6; the studies were repeated one year later in one of these patients. The exercise test with the heart in sinus rhythm was performed at the same work rate as that with the heart in atrial

Table ~Re.aturation Time Con•tant ( T) and Clearance Fraetion Durin« E%erei•e in Ten Patient• before and after Con11er•ion from Atrial Fibrillation to Sinu. Rhythm

Age (yr), Sex

Work Rate, kp-m/min

Rhythm*

Oxygen Uptake, ml/min

Heart Rate, beats per minute

seconds

Clearance Fraction, percent

T,

20,M

600

AF SR

1,840 1,680

186 144

1.3 1.4

25 30

31, F

100

AF SR

612 549

126 128

3.7 2.7

13 17

34, M

50

AF SR

430 600

126 102

5.0 4.2

10 14

36, F

0

AF SR

427 565

170 82

3.9 3.1

9 24

37, F

150

AF SR

655 623

174 132

1.0 1.4

35 32

44, F

150

AF SR

467 673

168 105

2.8 1.3

13 44

49, M

250

AF SR

832 889

152 103

2.3 4.7

17 12

49, M**

150

AF SR

105 480

160 96

2.4 2.1

16 30

50, M••

250

AF SR

832 754

150 102

2.4 2.4

17 25

51, F

150

AF SR

408 316

136 102

5.0 5.0

9 12

59, M

300

AF SR

632 935

167 114

3.0 1.8

12 29

AF SR

701 731

156 110

3.1 2.8

l6 25t

Mean

*AF, Atrial fibrillation; and SR, sinus rhythm. • •same patient. tDifference in clearance fraction is significant by paired t-test at level of P = 0.05.

CHEST, 70: 6, DECEMBER, 1976

NONINVASIVE MEASUREMENT OF CARDIAC FUNCTION 737

fibrillation, even when the patient was not limited by symptoms at that load. T was shorter or unchanged in seven of ten patients and the clearance fraction larger in eight of ten patients after sinus rhythm was restored. DISCUSSION

Measurements made from resaturation curves are analogous to those made from other indicator-dilution curves; 2 they correlate with clinical, radiologic, electrocardiographic, and hemodynamic measurements and give information based primarily on left heart function. The chief determinants of T are stroke volume, heart rate, and volume of the dominant mixing chamber between the lungs and the ear (ordinarily the left ventricle). Measurement of the clearance fraction eliminates one variable, heart rate, and provides a ratio that is related to left ventricular ejection fraction. To examine the relationship of resaturation curves to other measurements of cardiac function, we calculated correlation coefficients in two groups of patients selected on the basis of a clinical diagnosis of mitral stenosis or aortic valvular disease, comparing T and the clearance fraction with generally accepted indicators of the severity of valve disease. One would not expect, of course, that any single measurement would describe overail cardiac function, so it is not surprising that the correlation coefficients between independent variables were small. For example, the relationship between two direct measurements of left ventricular function, end-diastolic pressure and end-diastolic volume, is highly variable, 13 yet both give important information. Therefore, it is not surprising that a more general measurement of overall cardiac function, such as the resaturation curve, correlates more closely and with more variables than any other single direct measurement. This result indicates that resaturation curves are an index of functional status, rather than a parallel to the diagnostic information obtained by angiographic studies and cardiac catheterization. Pathophysiologic factors, such as pulmonary congestion, inadequate increase in cardiac output with exercise, mitral regurgitation, poor myocardial muscular performance, and cardiac arrhythmias, can be expected. to result in the same directional changes in resaturation curves and to be additive in their effects. Such a measurement of overall cardiac function complements the anatomically specific data obtained from invasive techniques and, being noninvasive, has the advantage that it may readily be performed many times to follow patients and assess the results of treatment. The results of serial studies in normal subjects and

738 GOODENDAY ET AL

clinically stable patients showed little change over a period of years, whereas serial studies in patients whose condition has changed (such as those studied before and after cardiac surgery) do demonstrate change, generally paralleling the clinical or hemodynamic status. Thus, resaturation curves are capable of detecting changes in cardiac function. The measurements used for correlation in this study were made at the highest work rate tolerated by the patients. Measurements recorded at rest or during low levels of exercise might not necessarily be so reliable or reproducible; however, at submaximal exercise levels sufficient to abolish the pulmonary ventilation-perfusion abnormalities seen at upright rest, the resaturation curve does provide information not available from a simple test of maximum exercise tolerance. The measurements of T and the clearance fraction at the maximum tolerated work rate may be compared to the patient's previous performance without the results being influenced by the patient's motivation to continue. They may also be compared with results obtained in normal subjects at similar work rates. Adequacy of the patient's effort may be determined by the finding of a logarithmic return of oxygen saturation to 100 percent. The ease with which the test is performed and the minimum equipment necessary are important factors; however, the use of an ear oximeter is obviously necessary. In the past the accuracy of ear oximetric studies has been questioned. The recent development of simple methods of measuring the oxygen pressure of respired gas 14 has made it possible to calibrate an ear oximeter in a noninvasive manner for each patient. 6 In subjects whose resting Sa02 can be assumed to reach 100 percent after three minutes of oxygen breathing and whose pulmonary function is not grossly impaired, calibration studies using arterial samples for comparison have shown that an ear oximeter can reliably measure Sa02 to within + 1 percent in the range of values from 90 to 100 percent and to within ±2 percent in the range of values from 80 to 90 percent. 6 Because the change in Sa02 with time, rather than the actual arterial saturation, is required to calculate a resaturation curve, the linearity of the response of the oximeter and not its absolute calibration is important. The response time of the oximeter is also important. Comparisons with simultaneous measurements using a cuvette to sample arterial blood have shown that the ear oximeter responds more rapidly, provided that sufficient time is allowed for the ear to become thoroughly warm. Employing an ear oximeter during strenuous work might also be considered to be liable to error, because redistribution of blood Bow to the exercising muscles might result in a diminished Bow of blood to

CHEST, 70: 6, DECEMBER, 1976

Because the resaturation curve is highly reproducible in an individual over many years, we believe that the most valuable use of the test is to follow the course of disease in individual patients, where a change in cardiac function may indicate the need for a change in therapy.

the ear; however, calibration studies during severe exercise, in which samples of arterial blood were compared with oximetric measurements, have shown no significant differences. 6 The specific advantages and disadvantages of measurements based on the resaturation curve have already been enumerated. 3 Their noninvasive nature, safety, and the ease with which they can be repeated with minimal inconvenience to the patient are important advantages. The most important disadvantage is that such measurements cannot be used reliably in patients who have significant obstructive pulmonary disease and maldistribution of ventilation or in patients who cannot abruptly raise oxygen pressure (after a breath of oxygen) due to right-toleft shunts or defects in diffusion. The recording of respired gas tensions during the test makes it possible to detect serious abnormalities in the distribution of ventilation. Inequalities in the distribution of pulmonary ventilation and perfusion tend to decrease with increasing tidal volume and pulmonary blood flow during exercise. 15 This makes measurement of resaturation curves less subject to error as the work rate increases. Provided that the test is performed during exercise and that the fall in Sa02 is limited to between 10 and 15 percent, the return of Sa02 to normal is exponential in more than 95 percent of normal subjects and patients who have no right-toleft shunt. In addition, the time constant of the resaturation curve is independent of the pattern of breathing and does not vary by more than 10 percent on repeated measurements in the same subject exercising at a constant heart rate at the same load. 3 With regard to safety, we apply the usual precautions taken for any test involving exercise stress of patients with cardiac disease; the presence of a physician and adequate resuscitative equipment is mandatory. In addition, it is theoretically possible that the investigator may inadvertently allow the patient to breathe a gas mixture low in oxygen content for a prolonged period. Because the physician is monitoring Sa02 in order to do the test, this possibility is unlikely, but recording end-tidal oxygen or nitrogen also helps prevent this. The test has proven completely safe in the 108 patients reported here, with no occurrence of syncope, ventricular tachycardia, myocardial infarction, or cardiac arrest. Among more than 1,000 tests, one patient studied for evaluation of coronary disease had a brief episode of ventricular tachycardia which subsided spontaneously.

1 Linhart JW, Turnoff HB: Pitfalls in diagnostic and functional evaluation using exercise testing (editorial). Chest 65:364-366, 1974 2 Bloomfield DA ( ed): Dye Curves : The Theory and Practice of Indicator Dilution. Baltimore, University Park Press, 1974, p 450 3 Mcilroy MB, Crawford DW, Jennings DB, et al: Assessment of cardiac function using resaturation curves. J Appl Physiol21 :1561-1567, 1966 4 Wahlund H: Determination of the physical working capacity: A physiological and clinical study with special reference to standardization of cardio-pulmonary functional tests. Acta Med Scand (suppl)215 :1-108, 1948 5 Newman EV, Merrell M, Genecin A, et al: The dye dilution method for describing the central circulation: An analysis of factOt"S shaping the time-concentration curves. Circulation 4:735-746, 1951 6 Friesen WO, Rosenhamer GJ, Mcilroy MB: Ear oximeter calibration using alveolar PO:! measurements. Scand J Clin Lab Invest 29:37-43, 1972 7 Ayotte B, Bogren H, Carlsson E, et al: Assessment of left heart function by noninvasive exercise test in normal subjects. J Appl Physiol34:644-649, 1973 8 New York Heart Association, Criteria Committee: · Diseases of the Heart and Blood Vessels: Nomenclature and Criteria for Diagnosis ( 6th ed ) . Boston, Little, Brown, and Co, 1964, p 463 9 Sokolow M, Lyon TP : The ventricular complex in left ventricular hypertrophy as obtained by unipolar precordial and limb leads. Am Heart J 37:161-186, 1949 10 Jonsell S: A method for the determination of the heart size by teleroentgenography : A heart volume index. Acta Radiol20:325-340, 1939 11 Weinberg GH, Schumaker JA: Statistics: An Intuitive Approach. Belmont, Calif, Wadsworth Publishing Co, 1962, p 200 12 Gorlin R, Gorlin SG: Hydraulic formula for calculation of the area of the stenotic mitral valve, and other cardiac valves, and central circulatory shunts. Am Heart J 41 :129, 1951 13 Dodge HT, Sandler H, Baxley WA, et al: Usefulness and limitations of radiographic methods for determining left ventricular volume. Am J Cardiol18:10-24, 1966 14 Friesen WO, Mcilroy MB: Rapidly responding oxygen electrode for respiratory gas sampling. J Appl Physiol 29:258-259, 1970 15 Jones NL, McHardy GJR, Naimark A, et al: Physiological dead space and alveolar-arterial gas pressure differences during exercise. Clin Sci 31 :19-29, 1966

CHEST, 70: 6, DECEMBER, 1976

NONINVASIVE MEASUREMENT OF CARDIAC FUNCTION 739

REFERENCES