Catheterization and Cardiovascular Diagnosis 11 :115-125 (1985)

Original Studies

Hemodynamic Evaluation of Stenotic Cardiac Valves: I . Effect of Ventriculography and Atropine on Mitral Stenosis

Juan Angel, MD, Enric Domingo, MD, J. Soler-Soler, MD, and lnocencio Anivarro, MD

Mitral area is the parameter used for quantitating mitral stenosis (MS) severity. When mitral gradient (MG) is low and reduction of mitral valve area (MVA) might be critical, interventions presumably increasing mitral valve flow (MVF), such as stress or atrial pacing, have been carried out. The purpose of this study was to analyze in 28 patients the combined effect of left ventriculography (LVG) and intravenous atropine (ATR) in the hemodynamic evaluation of MS. The rationale for combining these two interven- tions is to add up the ATR-positive chronotropic effect to the LVG potentiation of cardiac output. The LVG plus ATR markedly accelerated heart rate (from 80 f 14 to 104 f 18 btslmin, P < O.OOl), mildly increased cardiac index (from 2.6 f 0.6 to 2.9 f 0.6 l/min/m2, P < 0.05), and importantly increased MVF (from 136 f 30 to 172 f 46 mllbt, P < 0.001). Pulmonary wedge pressure increased (from 14 f 5 to 21 f 5 mmHg, P < 0.001) because of an important increment of MG (from 12 f 6 to 18 f 7 mmHg, P < 0.001). None of six cases with mild MS (MVA > 1.5 Cm2) and nine of ten cases with severe MS (MVA < 1.0 cm2) had MG after LVG plus ATR > 12 mmHg. The remaining case with severe MS and the two cases (out of 12) with moderate MS having MG after LVG plus ATR < 12 mmHg had, at surgical evaluation, noncritically reduced MVA.

This study shows that LVG plus ATR is a valid and easy intervention for increasing MVF during cardiac catheterization. It also allows the reclassification of patients with low baseline MG and reduced MVA into two subgroups: Cases with critically reduced MVA at surgery achieve a postintervention MG > 12 mmHg and those cases with noncritically reduced MVA achieve a postintervention MG < 12 mmHg.

Key words: atropine, mitral stenosis, ventriculography

INTRODUCTION

Measurement of the atrio-ventricular diastolic gradient generated by the mitral valve is the main goal of the hemodynamic evaluation of patients with mitral stenosis

From the Ciudad Sanitaria Val1 d’Hebron, Val1 d’Hebron SN, Barcelona, Spain.

Address reprint requests to Juan Angel, MD, Servicio de Cardiologia, Hospital General, Ciudad Sanitaria Vall d’Hebron, Po. Vall d’Hebron, SN, 08035 Barcelona, Spain.

Received September 20, 1984; revision accepted November 25, 1984.

0 1985 Alan R. Liss, Inc.

116 Angel et al

(MS). In many cases, the severity of MS can be accurately estimated by means of clinical and noninvasive methods [ 1,2]. However, in some patients, clinical features do not correlate with noninvasive findings. In such cases, cardiac catheterization for mitral valve gradient (MG) measurement and mitral valve area (MVA) calculation is mandatory [3,4]. When baseline mitral gradient (MG) is low, and valve area is at least moderately reduced, physiological interventions raising heart rate (HR) and cardiac output (CO) should be routinely carried out and the induced changes on MG evaluated. Basically, exertion [5-71 and rapid atrial pacing [8,9] have been used. Such interventions have both advantages and limitations. Exertion, which raises HR and CO, is a complicated maneuver when performed during cardiac catheterization in a premedicated recumbent patient with catheters crossing heart chambers and usually penetrating through one of the limbs involved in the exertion [lo]. Atrial pacing requires an additional catheter, does not raise CO, and is less effective in increasing mitral valve flow (MVF); furthermore, in patients on atrial fibrillation, pacing has to be performed in the right ventricle with even less definite effects on MVF (deleterious effect on CO). On the other hand, whenever cardiac catheterization is performed in MS, left ventriculography (LVG) is mandatory for mitral valve and left ventricular function evaluation. In the present paper, we have studied the hemo- dynamic effects of intravenous atropine (ATR) after LVG in patients with MS. Theoretically, this easy-to-do intervention could avoid the practice of exertion in the catheterization laboratory as atropine accelerates HR [ 111 and angiographic dye leads to intravascular fluid expansion [ 12, 131.

PATIENTS AND METHODS

Twenty-eight consecutive patients with MS undergoing cardiac catheterization were selected. The group consisted of 11 males and 17 females, aged from 24 to 64 years (mean 43) (Table I). Patients with moderate to severe mitral regurgitation, significant additional valvular disease (aortic and/or tricuspid), or coronary artery disease were excluded. Selective coronary arteriography was performed on patients older than 55 years and on those with clinical symptoms suggesting coronary artery disease.

Informed consent was obtained and catheterization was performed after premedi- cation with diazepan 5 mg and prometazine 25 mg i.m. Right heart catheterization was performed with a flow-directed triple lumen catheter with thermistor. Left heart catheterization was performed with a standard catheter suitable for LVG.

In all patients, simultaneous PW and left ventricular pressure (LV) were recorded very close to thermal dilution CO determination. The following parameters were analyzed: HR, cardiac rhythm, mean PW, LVEDP, mean diastolic PW-LV gradient (MG), cardiac index (CI) and stroke volume index (SVI). The MVF and MVA were calculated using already defined formulae [14]: MVF (ml/sec) = CO (L/min)/HR (beatdmin) X LVFT (sedbeat), MVA (cm2) = MVF (ml/sec) / 37.9 X J M G (mmHg), where LVFT is the left ventricular filling time.

In all patients the above-mentioned parameters were measured in baseline condi- tions (A) and after i.v. ATR following LVG (B). In 13 patients an intermediate control was also taken after LVG and before ATR administration.

Two Statham P23 Db transducers connected to an 8-channel Thomson Telco recorder were used. The PW and LV pressures were simultaneously recorded. In sinus rhythm, 3 to 5 beats of each recording were averaged; in atrial fibrillation,

TAB

LE 1.

Hem

odyn

amic

Dat

a in

28

Pat

ien

ts W

ith M

S: B

asel

ine

(A) a

nd A

fter

LVG

+ A

TR (

B)'

HR

(bt/m

in)

LVD

EP (m

mH

g) P

W (

mm

Hg)

M

G (

mm

Hg)

N

o.

Age

/sex

R

hvth

m

A

B A

1 55

F

2 56

M

3 61

F

4 43

F

5 33

M

6 43

F

7 54

M

8 31

F

9 47

F

10

52 M

11

51

F

12

47M

13

4

9F

14

44

M

15

30

F

16

64

F

17

52M

18

52

M

19

46

F

20

52 F

21

6

0F

22

49

F

23

36 F

24

24

F

25

40F

26

31

M

27

39M

S Fb

S Fb

Fb

Fb

Fb

S Fb

Fb

S Fb

Fb

Fb

S Fb

S Fb

S Fb

S S S S S S S S

66

105

87

90

97

104

80

94

110

140

85

145

110

140

101

109

89

100

53

98

90

100

68

112

75

140

82

105

90

105

85

100

75

100

64

80

95

96

90

108

86

90

76

98

74

120

68

84

70

100

64

72

70

100

7 4 1 3 8 10

4 4 7 10 4 8 10 8 2 6 8 8 8 10 5 8 6 7 8 16

11

6

B 8 8 3 7 8 6 5 2 8 10 6 5 5 7 4 9 8 12

4 10

10 7 1 11

10

16 9 8

-

A

12

17

16 6 18

14

25

27

10

11 4 5 18

10

12

16

12

12

23

23

15 8 8 10

12

14

12

12

-

B

28

22

18

16

25

22

25

29

15

16 8 12

25

12

15

18

20

18

28

28

28

21

12

13

25

20

31

22

-

A 9 15

15 7 15

10

24

27 7 6 3 4 15 4 10

15 8 11

19

18

16 7 5 6 11 9 10

10

-

B 28

21

16

12

26

16

26

33 9 15 4 10

22 9 12

16

18

12

32

26

26

14

12 6 25

13

19

20

~

CI

(L/m

in/m

2)

SVI (

ml/b

t/m2)

MV

F (m

l/sec

) M

VA

(cr

n2)

A

B

2.9

3.8

2.13

2.

53

1.81

2.

3 2.

6 3.

16

3.1

3.33

2.

47

2.63

2.

29

2.08

2.

98

3.0

1.91

2.

32

1.85

2.

22

3.0

3.4

2.8

3.5

2.52

2.

12

2.41

2.

54

3.6

3.4

2.7

2.6

2.65

3.

01

1.82

2.

03

2.93

2.

73

2.57

2.

45

3.1

3.1

2.13

2.

82

3.4

3.8

2.9

3.4

2.55

3.

8 3.

2 3.

5 2.

8 2.

9 3.

13

3.38

A

BA

BA

B

44

24.5

19

32

.5

28.2

29

.1

20.7

29

.5

21.5

34

.9

33

41.3

33

.5

29.3

40

32

35

28

.4

30.9

28

.6

36

28

46

42.6

34

51

.6

40.2

36

144

28.1

10

8 23

92

38

.3

125

23.8

19

5 18

.1

126

14.8

12

6 27

.6

124

23

105

22.7

95

34

19

5 30

12

1 16

87

25

12

5 32

.3

204

26

144

30

118

25.4

11

3 28

.8

154

22.7

13

3 34

.4

, 15

2 30

10

5 32

15

7 40

.5

151

38

138

48.6

16

7 29

15

6 49

.6

37.6

14

4

210

1.27

1.

05"

125

0.74

0.

72"

130

0.63

0.

86"

170

1.25

1.

3b

303

1.33

1.

57

152

1.05

1.

0"

113

0.68

0.

58"

137

0.63

0.

63a

148

1.05

1.

3b

151

1.02

1.

03

220

2.98

2.

9 21

6 1.

6 1.

8 10

1 0.

59

0.57

" 16

5 1.

65

1.45

21

0 1.

7 1.

6 14

0 0.

98

0.92

" 15

9 1.

1 0.

99

114

0.9

0.87

b 14

4 0.

93

0.67

a 14

7 0.

83

0.76

a 16

0 1.

0 0.

83"

187

1.05

1.

32"

226

1.85

1.

72

167

1.63

1.

8 26

5 1.

1 1.

4 19

1 1.

47

1.4

165

1.3

1.0

195

1.2

1.15

28

35

M

-

63

90

~~

*F, f

emal

e; M

, mal

e; S

, si

nus;

Fb,

fib

rilla

tion.

a~

~~

< 1.0

cm

2 at s

urge

ry.

b~~~

>

1.0

cm2 a

t sur

gery

.

118 Angel et a1

averages included 5 to 10 beats. PW was taken through the distal lumen of the right- sided catheter while the distal tip was in a pulmonary artery branch. With the balloon inflated [ 151, confirmation of a correct PW was assured when deflation of the balloon resulted in a morphologically different pressure tracing with higher mean. Pressure range and recording velocity were set individually in order to obtain an area of diastolic PW-LV gradient as large as possible. Mean diastolic gradient was calculated by means of planimetry. The CO was measured by thermo-dilution with an Edwards 9520 A computer just after PW-LV pressure recordings were obtained. The CO final value was calculated by averaging the results of five curves.

The LVG was performed in a 30” RAO projection. Seventy-eight percent iotalamate was injected in varying amounts ranging from 45 to 60 ml at a rate of 15-20 ml/sec. In all patients, 1 mg i.v. bolus of atropine sulfate was injected 3 to 5 minutes after LVG. Whenever HR acceleration was smaller than 10 beatdmin, a second 1-mg dose was injected (eight patients) 2 minutes later. The previously stated parameters were measured again 2 minutes after drug administration.

Fifteen patients were operated on and MVA was estimated by the surgeon by means of a probe: MS was considered severe or critical when the valve area was estimated at < 1 cm2 and noncritical when valve area was > 1 cm’.

Data Analysis

The Student’s paired t-test was used for evaluation of changes on the above- mentioned parameters from A to B.

Changes of CI, HR, MVF, PW, and MG were analyzed depending on the degree of MS severity graded according to baseline MVA (mild MS: MVA > 1.5 cm2); severe MS: MVA 6 1.0 cm2; moderate MS: between 1 and 1.5 cm2); group compar- isons were done using the Student’s t-test for grouped data.

The exact probability test of Fisher was used for comparing baseline MVA and post LVG + ATR MG versus surgical estimation of MVA.

The level of significance was always set at 5 % .

RESULTS

Individual results are displayed in Table I. In all cases, atropine-induced HR acceleration (A: 80+ 14 beatdmin, B: 104+ 18

beatdmin, P < 0.001) (Fig. 1) . As shown in Figure 1, LVEDP was unchanged after LVG plus ATR (7 k 3 mmHg,

A and B). The PW increased consistently after LVG plus ATR (A: 14 f 5 mmHG; B: 21 +

5 mmHg, P < 0.001) (Figs. 2-4). The PW-LV mean diastolic gradient (MG) (A: 12 f 6 mmHg) increased signicantly

after LVG plus ATR (B: 18 f 7 mmHg, P < 0.001) (Figs. 2-4). The decrease of SI after LVG plus ATR was not significant (A: 33 f 9 vs B: 27 f

10 ml/beat/m’; on the contrary, CI was mildly but significantly increased (A: 2.6 f 0.6 vs B: 2.9 f 0.6 L/min/m2, P < 0.05) (Fig. 5).

The MVF (A = 136 f 30 ml/sec) was increased importantly after LVG + ATR (B: 172 f 46 ml/sec, P < 0.001) (Fig. 6).

The MVA did not change (A: 1.20 f 0.48 cm’, B: 1.19 f 0.50 cm’). The average change was 0.02 f 0.1 cm’.

Mitral Stenosis: Effect of Atropine and Ventriculography 119

HEART RATE (beats/min)

L V E D P (mm Hg)

A B Fig. 1. Behavior of HR and LVEDP before (A) and after (B) LVG + ATR. HR significantly increased while LVEDP did not change. Figures 1,2, and 5-7 display mean and SD as horizontal and vertical bars respectively; solid dots represent patients on atrial fibrillation; open circles represent sinus rhythm.

P W PRESSURE (rnrn. Hg)

A B

MITRAL GRADIENT (mm. Hg)

A 0

Fig. 2. PW pressure and mitral gradient before (A) and after (B) LVG + ATR; both parameters significantly increased.

The behavior of the above parameters did not depend on heart rhythm since it was similar for both patients in sinus rhythm and atrial fibrillation (Figs. 1-6).

The increase of CI after LVG plus ATR was significantly smaller in the ten cases with severe MS (0.04 k 0.30 L/min/m2) than in the 12-cases with moderate MS (0.47 f 0.30 L/min/m2) or in the six mild MS (0.32 f 0.30 L/min/m2) (P < 0.01) (Table I). There were no significant differences in HR increments depending on MS severity (mild MS = 26 f 16 beats/min; moderate MS = 28 f 15 beats/min; severe MS = 17 f 19 beatdmin). The MVF increments after LVG + ATR were signifi- cantly smaller in severe MS (8 k 15 ml/sec) than in moderate MS (56 f 35 ml/sec,

120 Angel et al

Fig. 3. Simultaneous recording of PW and diastolic LV pressure (patient 25). Mitral gradient is shaded. A: baseline tracings on sinus rhythm. B: after LVG, HR is unchanged and mitral gradient mildly increased. C: after LVG + ATR, both HR and gradient increased markedly.

Fig. 4. Simultaneous recording of PW and diastolic LV pressure (patient 10 on atrial fibrilla- tion). A: baseline tracings. 8: after LVG + ATR, showing a marked increase of both HR and mitral gradient.

P < 0.01) and mild MS (42 i- 34 ml/sec, P < 0.05) (Table I). The PW increments were small in mild (4 f 1.8 mmHg) and severe MS (4.7 Ifr 3.6 mmHg) while considerably more marked (10 i- 4 mmHg) in moderate MS (P < 0.01) (Fig. 7). The MG increased mildly in mild MS (2.5 f 2.4 mmHg), moderately in severe MS (5.5 i- 4.2 mmHg, P < 0.05 vs mild MS), and importantly in moderate MS (8.8 i- 4.6 mmHg, P < 0.05 vs mild and P < 0.05 vs severe MS) (Fig. 7).

Twelve of the 15 cases with surgical MVA evaluation (Table I) had MVA critically reduced (< 1.0 cm2). All 12 had LVG + ATR MG > 12 mmHg, while only nine of

Mitral Stenosis: Effect of Atropine and Ventriculography 121

STROKE INDEX ( ml/beat/d)

N 5

A B

CARDIAC INDEX ( L / m i n / m ’ )

P(O.05

A B

Fig. 5. Behavior of stroke volume and cardiac index before (A) and after (B) LVG + ATR. The procedure caused a nonsignificant decrease in stroke index and a significant increase in cardiac index.

M I T R A L VALVE FLOW

300

250

2m

150

100

A

t /

/

0:0001

B

Fig. 6. MVF before (A) and after (6) LVG + ATR. As expected, MVF was substantially increased after the intervention.

122 Angel et al

MITRAL GRADIENT PW PRESSURE (mm. H d

MILD MODERATE

1 2

A ; 4 T f 3 6

$ -t------t A B

SEVERE

3

mm. HG A;881146 l W O O 1 3or005

m 2

WOERATE

A = 5 5 f 4 2 Io<005

ii! 7 A

3 SEVERE

Fig. 7. PW pressure and mitral gradient before (A) and after (B) LVG + ATR. Patients are classified into three groups according to mitral stenosis severity. Moderate stenosis showed the greater increase in both parameters. Horizontal bars define critical PW and mitral gradient which separate mild from moderate and severe stenosis.

them had the hemodynamic MVA 6 1.0 cm2. The remaining three cases with noncritically reduced surgical MVA had LVG + ATR MG < 12 mmHg, while only two had the hemodynamic MVA > 1 .O cm’. The exact probability test of Fisher only showed a good correlation between surgical MVA evaluation and LVG + ATR MG, P < 0.01 (Fig. 8). When the six patients with mild MS are added to the surgically evaluated cases (assuming that all six really had an MVA > 1.0 cm2), the group is expanded to 21 cases. The statistical analysis of these 21 cases showed some degree of correlation between surgical and hemodynamic MVA estimation (P < 0.05); however, the correlation between surgical MVA and LVG + ATR MG was further increased (P < 0.001) (Fig. 8).

DISCUSSION

Exercise is without doubt the most suitable maneuver to reproduce, in the cardiac catheterization laboratory, the behavior of MG and PW during physical stress. Exercise is known to increase PW and MG in patients with MS through two mecha- nisms: shortening of diastolic LV filling period (secondary to HR increase) and CO augmentation [5-71. However, a stress test is time consuming, technically difficult, and cumbersome to perform during cardiac catheterization [ 101.

Rapid atrial pacing has been considered a valid alternative intervention, but this procedure has several disadvantages: An additional catheter for atrial stimulation is necessary and it is less effective than exercise since it does not induce any increase in CO because of a consistent decrease of stroke volume [8,9]. In addition, when atrial fibrillation is present, ventricular pacing has to be performed with its known CO reduction and consequently with its less marked increment in MVF [16, 171. The above-mentioned shortcomings are avoided by our intervention (LVG plus ATR)

Mitral Stenosis: Effect of Atropine and Ventriculography 123

MVA HEMODYNAMIC M G ( A N G t A T R ) MVA SURGERY

NOT OPERATED

Fig. 8. Classification of 15 operated-on patients by means of three different criteria. Left: hemodynamic MVA estimation; middle: MG after LVG + ATR; right: surgical MVA estimation. Upper level: critical MS; lower level: noncritical MS. The group is expanded to 21 cases assuming that six cases with hemodynamic MVA > 1.5 cm2 and MG after LVG + ATR < 12 mmHg, not operated on, would have had surgical MVA > 1 cm2. Solid circles, MVA critically reduced at surgery: open circles, MVA noncritically reduced at surgery.

which is easily carried out by means of a bolus of i.v. ATR as the only additional procedure, since LVG is part of the routine hemodynamic evaluation of MS. Table I and Figure 2 clearly display that this intervention causes marked increments in PW and MG independently of patient cooperation or heart rhythm. These changes are due to a marked increase of MVF (Fig. 6) secondary to the induced increments in HR (mainly due to ATR) and CO (mainly through the intravascular fluid expansion effect of contrast media and HR acceleration) [12,13]. The negative ATR effect on SI is significantly lower in recumbent than in orthostatic patients [ 181. Although dye contrast may act as a myocardial depressor [12,13], this effect must not be important in patients with MS, since most of them have a normal functionning myocardium. In our patients, the observed increase in LVEDP after LVG might suggest a negative effect on myocardial function. However, the increase in LVEDP was brought back to baseline values with ATR effect (Table 11).

The effects of LVG + ATR intervention were different depending on MS severity. In mild stenosis, increments of MVF (CI and HR) were not followed by marked PW and MG changes because the mitral area was not critically reduced. In severe stenosis, PW and MG increments were mild, probably due to the initially high PW and MG levels and to the less marked changes of MVF. In severe MS, MVF increments are not important and they are accomplished mainly through HR acceleration; a similar behavior during exercise has been attributed to the inability of reduced MVA to allow MVF increments [4,19]. Patients with moderate MS, when considered as a whole group, behaved as mild MS in terms of MVF increments despite generally important PW and MG changes (Figs. 3,4). However, a subgroup with post LVG+ATR MG < 12 mmHg and noncritically reduced MVA at surgery was identified (Fig. 8). When considering the 15 cases operated on, the correlation of surgical MVA was not significant versus hernodynamic MVA and significant versus MG after LVG + ATR

124 Angel et al

TABLE 11. Changes of Hemodynamic Parameters After LVG and LVG Plus ATR in 13 Patients.

Significance A LVG B A-LVG LVG-B

HR (beatdmin) 76 f 11 73 f 8 99 f 18 LVEDP (mmHg) 8 f 3 13 f 4 8 * 4 pw ( M g ) 14 f 4 20 f 5 22 f 4 MG (mmHg) 12 f 5 14 f 5 18 f 7 SI (ml/beat/m2) 36 f 8 40 f 9 32 f 9 CI (L/min/m*) 2.8 f 0.5 2.9 f 0.5 3.1 f 0.5 MVF (ml/sec) 146 f 25 156 f 31 179 f 40 MVA (cm’) 1.24 f 0.33 1.22 f 0.39 1.20 f 0.39

*A, baseline; LVG, after left ventriculography; B, after LVG plus ATR.

NS P < 0.01 P < 0.001 P < 0.05 P < 0.05

NS NS NS

P < 0.001 P < 0.01

NS P < 0.01 P < 0.01 P < 0.05 P < 0.05

NS

(P < 0.01). When the group is expanded with six mild not-operated-on MS, the correlation improved for both, P < 0.05 and P < 0.001 respectively.

The lack of MVA changes with interventions that modify some parameters involved in its calculation has been reported with stress [6,7,20]. Our results confirm these findings as baseline post-LVG plus ATR MVA values show very small differences (0.02 k 0.1 cm2). This reproducibility validates the consistency of this hemodynamic parameter. However, the clinical usefulness of the hemodynamic MVA estimation remains controversial in the group of patients with a moderately reduced MVA. Five of our patients with moderate MS were operated on. The MVA was considered critically reduced in three and noncritically reduced in two by the surgeon. Baseline MG ranged from 7 to 10 mmHg in these five patients. The three patients with surgically estimated critically reduced MVA had LVG + ATR MG > 12 mmHg (14, 16, and 28 mmHg), while the remaining two with surgically estimated noncritically reduced MVA had LVG+ATR MG < 12 mmHg (9 and 12 mmHg) (see patients 1, 4, 6, 9, and 22 in Table I). The only patient with severe MS who had LVG+ATR MG Q 12 mmHg had MVA noncritically reduced at surgery (patient 18): In fact, critically reduced MVA at surgery was better predicted by behavior of MG after LVG+ATR than by hemodynamic MVA (Fig. 8). Therfore, MG estimation after LVG + ATR should be considered clinically useful, especially in moderate MS. When MG after LVG+ATR is > 12 mmHg, MVA can be considered critically reduced.

CONCLUSIONS

The present study suggests that intravenous administration of ATR after LVG is a useful and valid intervention in the hemodynamic evaluation of MS. The induced LVG + ATR MVF increments allow the reclassification of patients with moderately or severely reduced hemodynamic MVA and low baseline MG into two subgroups. Those cases with critical MS achieve a postintervention MG > 12 mmHg and those cases with noncritical MS achieve a postintervention MG Q 12 mmHg.

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Mitral Stenosis: Effect of Atropine and Ventriculography 125

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