International Journal of Cardiology, 37 (1992) 7-13 0 1992 Elsevier Science Publishers B.V. All rights reserved
CARD10
0167.5273/92/$05.00
01520
Cardiopulmonary exercise testing early after catheter-balloon mitral valvuloplasty in patients with mitral stenosis Eulogio E. Martinez a, Turibio L. Barros a, Dirceu V. Santos a, Antonio C. Carvalho Angelo A. de Paola a, Jose L. Andrade ‘, Japy Angellini ‘, Valter C. Lima ‘, Roberto R. Roberti a,b, Oscar P. Portugal a and Warren Sherman b ” DiGsion
‘,
of Cardiology. Escola Paulista de Medicina, Sao Paula, Brazil; ’ Department of Medicine, DiGsion of Cardiology, Mount Sinai Hospital, New York. W USA (Received
3 October
1991; revision accepted
7 May 1992)
Martinez EE, Barros TL, Santos DV, Carvalho AC, De Paola AA, Andrade JL, Angellini J, Lima VC, Roberti RR, Portugal OP, Sherman W. Cardiopulmonary exercise testing early after catheter-balloon mitral valvuloplasty in patients with mitral stenosis. Int J Cardiol 1992;37:7-13. Seven female patients (age 27 to 53 yr) with significant mitral stenosis performed continuous, incremental, maximal treadmill exercise tests the day before and within 3-5 days after catheter-balloon valvuloplasty. Mitral valve area determined by the echo-Doppler method increased from 0.9 k 0.3 cm2 to 1.9 k 0.7 cm2 (p < 0.02). Mean left atria1 pressure was reduced from 24 + 8 to 13 + 7 mmHg (p < 0.011 and mean pulmonary artery pressure from 36 A 13 to 28 k 10 mmHg (p < 0.02) with a non-significant increase in cardiac output from 3.6 1- 1.2 to 4.0 &-1.7 l/min. After catheter-balloon valvuloplasty all patients reached a higher maximal workload during exercise, and mean value of oxygen consumption and pulmonary ventilation were significantly lower in submaximal workloads. The calculated ventilatory equivalent for oxygen was significantly reduced in submaximal and in maximal workloads after catheterballoon valvuloplasty. Peak oxygen consumption and the ventilatory anaerobic threshold were not changed after catheter-balloon valvuloplasty (pre 15.59 k 2.72 vs post 16.90 + 3.44 and pre 12.10 + 2.55 vs post 12.62 + 2.71 ml/kg/min, respectively). We concluded that after catheter-balloon valvuloplasty the cost of breathing was reduced and the oxygen consumed was more effectively utihzed during exercise. Increases in peak oxygen consumption and in ventilatory anaerobic threshold would require circulatory and metabolic adaptations in response to increased physical activity and were not observed when cardiopulmonary tests were performed early after catheter-balloon valvuloplasty. Key words: Mitral valvuloplasty; Mitral stenosis
Correspondence to: Dr. W. Sherman, Catheterization Laboratory, Beth Israel Medical Center, 11th D., First Ave. at 16th St., New York, NY 10003, USA. Reprint requests to: Dr. E.E. Martinez, R. Escobar Ortiz 699, Sao Paulo. Brazil 04512.
Introduction Catheter balloon valvuloplasty has yielded striking improvement of symptoms in patients with severe rheumatic mitral stenosis [1,2]. Fol-
low-up studies are [2,31 encouraging for a persistence of hemodynamic benefit. Quantitative evaluations of symptomatic improvement following catheter-balloon valvuloplasty, have however, received little attention. Exercise duration was observed to increase 3 months after catheter-balloon valvuloplasty [4]. When mitral flow velocity was measured during graded exercise before and 5 days after catheter-balloon valvuloplasty, significant increases were observed [5]. Cardiopulmonary exercise testing has been used in the evaluation of patients with heart disease [6,7]. In this study, we submitted 7 patients with mitral stenosis to cardiopulmonary exercise, testing the day before and within 5 days after catheter-balloon valvuloplasty. Our purpose was to evaluate the impact of increased mitral valve area on exercise performance. In using these techniques we had the opportunity to evaluate changes in exercise performance which were independent of changes in physical activity (training) and life-style factors.
technique were performed before and after catheter-balloon valvuloplasty. Left heart catheterization with a 7 French pigtail catheter was performed via the femoral approach. Left ventriculography was performed before and after catheter-balloon valvuloplasty. Catheter-balloon valvuloplasty was performed by the antegrade double balloon method. An 8 French transseptal sheath (USC1 Corporation, Billerica MA) was introduced into the left atrium. Through this, a 7 French end-hole balloon flotation catheter was advanced through the left ventricle to the descending aorta. This was exchanged for a double lumen catheter (Cordis Corporation, FL) and then two 0.035 inch exchange guidewires. The interatrial septum was first dilated (8 mm balloon) followed by the mitral valve - a combination of a 15 mm and a 20 mm balloon in 4 patients, and two 20 mm balloons in 3 patients (Mansfield Scientific, Watertown MA). Hemodynamic calculations
Materials
and Methods
Patient population
Right and left heart pressures were recorded, and mitral valve area was calculated [8] before and after catheter-balloon valvuloplasty.
The patient population consisted of 7 females, all in New York Heart Association class 2 or 3 for heart failure with predominant mitral stenosis by clinical evaluation. All patients were without other medical diseases and were entered consecutively into this study. Informed consent was obtained from all patients and the protocol was approved by the hospital’s ethics committee. At baseline, all were in normal sinus rhythm. Mild mitral regurgitation was present in 1 patient and minimal aortic regurgitation was present in 4. The remainder were without any other significant valvular regurgitation.
Two-dimensional and Doppler echocardiographic studies were performed with ATL MK600 (Seattle, WA) equipment. Mitral valve area was calculated by the pressure half-time method [9]. Values represent ‘the average obtained from several beats. For the detection of atria1 septal defect the sample volume was placed on the right atria1 side of the interatrial septum in the subcostal and parasternal right ventricular inflow tract views.
Catheterization and valvuloplasty protocol
Exercise tests
Right heart catheterization using a 7 French thermodilution catheter was performed via a transjugular or transfemoral approach. Multiple site oximetry for the measurement of atria1 septal defects and cardiac output by the thermodilution
Patients performed continuous incremental, maximal, treadmill exercise tests the day before and within 5 days after mitral valvuloplasty. The protocol was developed based on an energetic cost normogram in which the load increase in
Echo-Doppler studies
Y
each stage approached one MET (3.5 ml/kg/min of oxygen consumption). For this protocol modest increments in workload occur every 3 min [lo]. In the last 30 s of each stage the following variables were measured: (1) systolic and diastolic arterial pressure (mmHg); (2) heart rate (beats/ mitt) through the average of 10 R-R intervals on the electrocardiogram; (3) pulmonary ventilation in l/min of body temperature pressure saturated, obtained by the expired air collection in a Tissot gassometer (Collins, USA) through a low resistance respiratory mask (Vacumed, USA); (4) oxygen consumption and carbon dioxide production standard temperature pressure dry expressed in ml/kg/min, obtained by the respiratory method through the analysis of samples of the expired air in an M-11 oxygen analyzer and an LB-2 carbon dioxide (Beckman, USA). For each exercise test we determined the following. (1) Peak oxygen consumption, corresponding to the highest attained oxygen consumption in each test. (2) Ventilatory anaerobic threshold, determined by the ventilatory method [lo] from analysis of the relationships of pulmonary ventilation with oxygen consumption and carbon dioxide production. The level of oxygen consumption beyond which pulmonary ventilation increased out of proportion as compared to the
TABLE
Statistics Data were analyzed by the Wilcoxon method for unmatched pairs and by the paired Student r-test, when applicable [l I]. The significance level was fixed at 0.05 (5%). Results Echo-Doppler and hemodynamic measurements (Table 1) Mitral valvuloplasty led to increases in Doppler mitral valve area from 0.9 f 0.3 cm’ to 1.9 f 0.7 cm* (p < 0.02) and to increases in valve area calculated by the Gorlin formula from 0.9 k 0.3 to 1.8 k 0.6 cm2 (p < 0.001). Mitral valvuloplasty provoked reductions in mean left atria1 pressure (from 24 f 8 to 13 k 7 mmHg, p < 0.01) and in
1
Echo-Doppler
and hemodynamic Dp v.a.
Mean SD p value
oxygen consumption increase, without increase in the pulmonary ventilation and carbon dioxide production relationship, was taken as the ventilatory anaerobic threshold. (3) Ventilatory equivalent for oxygen, expressed as the quotient between pulmonary ventilation and oxygen consumption was determined in each stage of the protocol.
measurements LAP mean
PAP mean
C.O.
mean Grad
Gorlin v.a.
pre
post
pre
post
pre
post
pre
post
pre
post
pre
post
1.4 1.3 0.7 0.9 0.8 0.7 0.6
2.7 1.4 2.4 1.5 1.4 1.0 2.7
27 17 23 40 14 26 25
18 10 09 11 05 21 17
48 22 21 48 22 44 50
32 20 18 30 20 30 45
2.5 4.2 4.9 5.2 2.9 2.9 2.5
2.6 3.9 1.2 5.6 3.1 2.8 3.0
15 14 17 2x 13 20 18
10 04 OX 07 04 10 04
1.2 1.1 1.2 1.o 0.X 0.6 0.6
2.1 2.0 2.6 2.2 1.6 0.9 1.5
0.9 0.3
1.9 0.7 < 0.02
24 08
13 07 < 0.01
36 13
28 10 < 0.02
3.6 1.2
4.0 1.7 < 0.05
18 05
0.9 0.3
1.8 0.6 < 0.001
07 03 < 0.005
Dp v.a. = mitral valve area by echo-Doppler km’): LAP mean = left atria1 mean pressure (mmHg); PAP mean = mean pulmonary arterial pressure (mmHg); C.O. = cardiac output (I/mm); mean Grad = mean gradient between left atrium and end-diastolic left ventricular pressure (mmHg); Gorlin v.a. = mitral valve area calculated by Gorlin formula (cm’): pre = values pre valvuloplasty: post = values post valvuloplasty.
10 TABLE 2 Mean values and standard deviations for age, anthropometric mitral valvuloplasty.
Mean SD
Age
Weight
Height
(yr)
(kg)
Cm)
53 40 34 31 27 46 28 37 9.8
73.0 58.4 55.2 47.3 48.5 46.3 38.8 52.5 11.0
1.60 1.58 1.60 1.57 1.51 1.58 1.50 1.56 0.04
findings and cardiopulmonary
Number of stages
responses to exercise pre and post
Peak V02 (ml/kg/min)
AT VOz (ml/kg/min)
pre
post
pre
post
pre
post
4.0 4.0 5.0 4.0 4.0 5.0 3.0 4.1 0.7
5.0 5.0 6.0 6.0 6.0 7.0 4.0 5.6 1.0
11.39 14.87 17.62 19.49 16.43 16.17 13.17 15.59 2.72
12.13 17.02 19.07 20.55 16.22 20.51 12.81 16.90 3.44
8.24 12.23 10.93 16.19 13.36 13.36 10.42 12.10 2.55
8.38 14.98 11.72 15.03 13.76 14.74 9.75 12.62 2.71
Peak VO, = peak oxygen consumption; AT VO, = ventilator-y anaerobic threshold.
mean pulmonary artery pressure (from 36 f 1.3 to 28 & 10 mmHg, p < 0.02). No significant changes in cardiac output occurred with catheterballoon valvuloplasty (from 3.6 f 1.2 to 4.0 f 1.7 l/min>. In 2 patients, after catheter-balloon valvuloplasty, small atria1 septal defects were detected by the echo-Doppler technique that were not detected by oximetric measurements. Exercise tests Exercise tests were accomplished without complications in all patients before and after mitral valvuloplasty. After valvuloplasty all patients reached a higher maximal workload (Table 2). When comparing pre- and post-valvuloplasty measurements, there were no significant differences in mean values for heart rate or for systolic and diastolic blood pressures during the exercise protocol (Table 3).
As shown in Table 2, there was no significant increase in peak oxygen consumption when we compared pre- (15.59 + 2.72 ml/kg/min) and post- (16.90 _t 3.44 ml/kg/min) valvuloplasty values. Furthermore, there was no significant change in mean values of ventilatory anaerobic threshold when we compared pre- (12.10 & 2.55 ml/kg/ min) and post- (12.62 k 2.71 ml/kg/min) valvuloplasty exercise tests. Mean values of oxygen consumption were significantly higher in the first three stages of the exercise protocol when we compared pre- and post-valvuloplasty exercise tests (Table 4 and Fig. 1). Mean values of pulmonary ventilation were significantly higher in the first 3 stages of the exercise protocol when we compared pre- and post-valvuloplasty tests (Table 4 and Fig. 2). In Table 4 values corresponding to the fourth stage of the exercise protocol represent the mean of 6 patients, because 1 patient was unable to perform
TABLE 3 Mean values and standard deviations for heart rates and arterial blood pressure pre and post mitral valvuloplasty. No. of patients
Stage
7 7 7 6
1 2 3 4
Systolic arterial pressure (mmHg)
Heart rate (beats/min) Pre
Post
120.28 + 18.33 136.86 + 20.60 142.43 & 22.56 157.50 f 20.08
110.57 f 120.86 + 133.57 * 148.17 +
14.80 14.23 15.63 13.07
Pre
Post
122.85 & 21.38 117.14 f 24.97 112.85 f 20.58 114.17 f 24.17
115.71 + 112.85 f 114.28 i 118.33 f
Diastolic arterial pressure CmmHg) Pre
7.86 11.13 12.72 14.72
81.43 + 80.00 f 78.57 + 77.50 +
Post 8.99 10.00 6.90 9.87
72.86 4 72.86 + 77.14 t 79.16 +
4.87 4.88 7.56 6.63
11
16,
42
1 5-
41.
1 4.
40.
-&
39.
\p
3.3.
Y -m
37.
> ’
36. 35 34
7. 6 0
0
4
2
Stages
of
c z
15
y
10
Exercise
more than 3 stages before valvuloplasty. Mean values of VEO, were significantly higher in the last 3 stages of the protocol when we compared pre- and post-valvuloplasty tests (Table 4 and Fig. 3). Discussion The impact of percutaneous transvenous mitral valvuloplasty on exercise performance within 5 days of the procedure, was the main purpose of the present study. Our hemodynamic results were similar to those of previous reports [1,2]: a significant increase of mitral valve area together with a decrease of left atria1 pressure as well as a reduction of mean pulmonary artery pressure.
5
Ok
4
2 Stages
of
Exercise
Fig. 2. Pulmonary ventilation (VE) in 7 patients at stages 1, 2 and 3, and in 6 patients at stage 4; pre (0) and post (+ ) catheter-balloon valvuloplasty (CBV).
TABLE
of
Fig. 3. Ventilatory equivalent for 0, (VEO,) expressed as the quotient between pulmonary ventilation WE) and oxygen uptake 0’0,) in 7 patients at stages 1, 2 and 3. and in 6 patients at stage 4: pre ( q 1 and post ( + ) catheter-balloon valvuloplasty (CBV).
25
20
4
2
Stages
Exercise
Fig. 1. Oxygen uptake NO,) pre (0) and post (+) catheter(CBV) in 7 patients at stages 1, 2 and 3, balloon valvuloplasty and in 6 patients at stage 4 of the exercise treadmill protocol.
; .-
k
I
331
4
Mean values valvuloplasty.
and
No. of patients
Stage
7 7 7 b
1 2 3 4
standard
deviations
respiratory
VO, (ml/kg/min) Pre
VO, = minute
for
10.15 12.14 13.92 15.31
2.41 2.00 2.16 2.33
oxygen consumption:
during
cardiopulmonary
VE U/mitt)
7.68 9.84 12.29 14.14
f + f *
2.63 * 1.83 * 2.08 * 2.20
VE = minute
ventilation;
+ + + +
3.47 3.97 3.75 4.79
VEO,
testing
pre
and
post
mitral
14.45 16.94 20.62 24.91
= ventilatory
Post
Pre
Post
20.29 24.27 27.94 32.11
exercise
VEO>
Pre
Post f + f f
factors
f k k k
4.95 * 3.38 * 4.40 * 6.28 equivalent
40.31 39.49 39.70 39.53
i * + +
7.27 3.91 3.66 4.12
for oxygen:
38.13 34.94 34.00 34.04
* p < 0.05
+ 3.04 _t 3.28 * + 4.30 * + 4.84 *
12
After mitral valvuloplasty all patients exercised to a higher maximal workload beyond the ventilatory anaerobic threshold which occurred on average at 77.5 and 74.9% of peak oxygen consumption pre and post valvuloplasty, respectively. Peak oxygen consumption values pre and post mitral valvuloplasty were similar in spite of a marked reduction in resting left atria1 pressure. These findings led us to the assumption that the high left atria1 and pulmonary venous pressures of mitral stenosis do not limit peak oxygen uptake during exercise. Additionally, the finding of similar peak VO, values when comparing exercise tests performed before and soon after valvuloplasty, suggests that the observed changes in cardiopulmonary response were not due to a training effect. High values for oxygen uptake at lower workloads may be attributed to higher cost of breathing secondary to hyperventilation and to the reduced pulmonary compliance resulting from pulmonary venous hypertension observed in mitral stenosis [12]. The mean values for oxygen consumption and for pulmonary ventilation were significantly lower at the first three stages of the exercise protocol after mitral dilatation. The increased ventilatory response to exercise in patients with mitral stenosis has been attributed to enhanced chemical or chemoreceptor drive [13,14], to tachypnea secondary to decrease in lung compliance [15] and to pulmonary congestion leading to stimulation of juxtapulmonary capillary receptors [16]. After successful commissurotomy, exercise ventilation was significantly reduced [17]. Reduced exercise ventilation soon after valvuloplasty together with a reduced oxygen consumption in each stage of exercise may be explained by an attenuation of the aforementioned mechanisms. All of our patients were able to complete a greater number of stages of the exercise protocol after valvuloplasty. Exercise duration correlates well with severity of mitral stenosis, determined at cardiac catheterization [l&19], and could possibly be utilized as an independent method of assessing early results of mitral valvuloplasty. Maximal heart rate achieved at peak exercise was found to be reduced after commissurotomy [17].
There has been some evidence that partial correction of the excessive increase in plasma catecholamine levels during exercise in patients with severe mitral stenosis, is responsible for reducing heart rate response to exercise [20]. Furthermore, mitral dilatation improves the ability to fill the ventricle and therefore via the Frank-Starling mechanism generates a larger stroke volume lowering the heart rate. Although not significant, there was a reduction in mean heart rate of approximately 10 beats/min in our patients for each stage of the exercise protocol after mitral valvuloplasty. Perhaps a larger number of patients would make this difference statistically significant. Conclusions Percutaneous transvenous mitral commissurotomy significantly improves hemodynamic parameters. In this group of patients we observed an increase in exercise capacity with lower oxygen uptake and lower pulmonary ventilation without change in peak oxygen consumption. We speculate that for each stage of the protocol the cost of breathing was reduced and the oxygen consumed was more effectively utilized during exercise. Increases in peak VO, require time for peripheral factors, such as muscle capillary density and oxidative enzyme activity, to increase in response to physical conditioning consequent to changes in life-style after successful mitral valvuloplasty. References 1 Inoue K, Owaki T, Nakamura T, Kitamura F, Miyamoto N. Clinical application of transvenous mitral commissurotomy by a new balloon catheter. J Thoracic Cardiovasc Surg 1984;87:394-402. 2 Palacios IF, Block PC, Wilkins GT, Weyman AE. Followup of patients undergoing percutaneous mitral balloon valvotomy. Analysis of factors determining restenosis. Circulation 1989;79:573-579. 3 Levine MJ, Erny RE, Leonard BM et al. Long term follow-up in 105 patients undergoing percutaneous balloon mitral valvuloplasty. J Am Co11 Cardiol 1989;13:18A. 4 McKay CR, Kawanishi DT, Kitlewski A et al. Improvement in exercise capacity and exercise hemodynamics 3 months after double-balloon, catheter balloon valvuloplasty treatment of patients with symptomatic mitral stenosis Circulation 1988;77:1013-1021.
5 Tamai J, Nagata S, Akaike M, Ishikura F, Yamagishi M, Miyatake K. Improvement in exercise hemodynamics after balloon mitral valvuloplasty: non-invasive examination using continuous wave Doppler. Circulation 1988;78 (suppl II) 4. 6 Weber KT. Kinasewitz CT. Janick JS: Fishman AP. Oxygen utilization and ventilation during exercise in patients with chronic cardiac failure. Circulation 1982;65:121312.31. 7 McElroy PA, Janicki JS, Weber KT. Cardiopulmonary exercise testing congestive heart failure. Am J Cardiol I988;67:35A-40A. 8 Gorlin R. Sawyer CG. Haynes PW. Goodale WT. Dexter L. Effects of exercise on circulatory dynamics in mitral stenosis. III. Am Heart J 1951:41:192-203. 9 Hatle L, Angelsen B. In: Doppler ultrasound in cardiology. 2nd Ed., Philadelphia: Lea and Febiger, 1985;118-128. IO American College of Sports Medicine. Guidelines for exercise testing and prescription. Philadelphia: Lea and Fehiger, 1986:179 pp. I I Siegel. S. Estatista uno pariametnica para ciencias do comportamento. McGraw Hill, 1981;350 pp. 12 White HC, Butler J. Donald KW. Lung compliance in patients with mitral stenosis. Clin Sci 3958;17:667-679. I3 Donald KW. Gloster J, Harris EA, Reeves J, Harris P. The production of lactic acid during exercise in normal
14
I5
I6 17
I8
I9
30
subjects and in patients with rheumatic heart disease. Am Heart J 1961;62:494-519. Cotes JE. The role of oxygen, carbon dioxide and lactic acid in the ventilatory response to exercise in patients with mitral stenosis. Clin Sci 1955;14:317-328. Palmer WH, Gee JBL. Mills FC, Bates DB. Disturbances of pulmonary function in mitral valve disease. Can Med Assoc J 1963;89:744-750. Paintal AS. Mechanism of stimulation F type J pulmonary receptors. J Physiol 1969:203:511-532. Reid JW, Ablet M, Cotes JE. Ventilatory responses to exercise and to carbon dioxide in mitral stenosis before and after valvulotomy: causes of tachypnea. Clin Sci Mol Med 197854% 16. Almendral JM. Garcia. Andocin JM, Schanez-Cascos A. DeRabogo P. Treadmill stress testing in the evaluation of patients with valvular heart disease: possible role in the assessment of functional capacity and severity of the Iesion. Cardiology 1982;69:42-51. Vacek JL, Valentin-Stone P, Wolfe M. Davis WR. The value of standardized exercise testing in the noninvasive evaluation of mitral stenosis. Am J Med Sci 1986;292:335343. Ikeda J. Haneda T. Canada H et al. The degree of increment in plasm catecholamine in patients with mitral stenosis by mild exercise. Am Heart J 1987:l l3:1103-I 107.
CARD10
0167.5273/92/$05.00
01520
Cardiopulmonary exercise testing early after catheter-balloon mitral valvuloplasty in patients with mitral stenosis Eulogio E. Martinez a, Turibio L. Barros a, Dirceu V. Santos a, Antonio C. Carvalho Angelo A. de Paola a, Jose L. Andrade ‘, Japy Angellini ‘, Valter C. Lima ‘, Roberto R. Roberti a,b, Oscar P. Portugal a and Warren Sherman b ” DiGsion
‘,
of Cardiology. Escola Paulista de Medicina, Sao Paula, Brazil; ’ Department of Medicine, DiGsion of Cardiology, Mount Sinai Hospital, New York. W USA (Received
3 October
1991; revision accepted
7 May 1992)
Martinez EE, Barros TL, Santos DV, Carvalho AC, De Paola AA, Andrade JL, Angellini J, Lima VC, Roberti RR, Portugal OP, Sherman W. Cardiopulmonary exercise testing early after catheter-balloon mitral valvuloplasty in patients with mitral stenosis. Int J Cardiol 1992;37:7-13. Seven female patients (age 27 to 53 yr) with significant mitral stenosis performed continuous, incremental, maximal treadmill exercise tests the day before and within 3-5 days after catheter-balloon valvuloplasty. Mitral valve area determined by the echo-Doppler method increased from 0.9 k 0.3 cm2 to 1.9 k 0.7 cm2 (p < 0.02). Mean left atria1 pressure was reduced from 24 + 8 to 13 + 7 mmHg (p < 0.011 and mean pulmonary artery pressure from 36 A 13 to 28 k 10 mmHg (p < 0.02) with a non-significant increase in cardiac output from 3.6 1- 1.2 to 4.0 &-1.7 l/min. After catheter-balloon valvuloplasty all patients reached a higher maximal workload during exercise, and mean value of oxygen consumption and pulmonary ventilation were significantly lower in submaximal workloads. The calculated ventilatory equivalent for oxygen was significantly reduced in submaximal and in maximal workloads after catheterballoon valvuloplasty. Peak oxygen consumption and the ventilatory anaerobic threshold were not changed after catheter-balloon valvuloplasty (pre 15.59 k 2.72 vs post 16.90 + 3.44 and pre 12.10 + 2.55 vs post 12.62 + 2.71 ml/kg/min, respectively). We concluded that after catheter-balloon valvuloplasty the cost of breathing was reduced and the oxygen consumed was more effectively utihzed during exercise. Increases in peak oxygen consumption and in ventilatory anaerobic threshold would require circulatory and metabolic adaptations in response to increased physical activity and were not observed when cardiopulmonary tests were performed early after catheter-balloon valvuloplasty. Key words: Mitral valvuloplasty; Mitral stenosis
Correspondence to: Dr. W. Sherman, Catheterization Laboratory, Beth Israel Medical Center, 11th D., First Ave. at 16th St., New York, NY 10003, USA. Reprint requests to: Dr. E.E. Martinez, R. Escobar Ortiz 699, Sao Paulo. Brazil 04512.
Introduction Catheter balloon valvuloplasty has yielded striking improvement of symptoms in patients with severe rheumatic mitral stenosis [1,2]. Fol-
low-up studies are [2,31 encouraging for a persistence of hemodynamic benefit. Quantitative evaluations of symptomatic improvement following catheter-balloon valvuloplasty, have however, received little attention. Exercise duration was observed to increase 3 months after catheter-balloon valvuloplasty [4]. When mitral flow velocity was measured during graded exercise before and 5 days after catheter-balloon valvuloplasty, significant increases were observed [5]. Cardiopulmonary exercise testing has been used in the evaluation of patients with heart disease [6,7]. In this study, we submitted 7 patients with mitral stenosis to cardiopulmonary exercise, testing the day before and within 5 days after catheter-balloon valvuloplasty. Our purpose was to evaluate the impact of increased mitral valve area on exercise performance. In using these techniques we had the opportunity to evaluate changes in exercise performance which were independent of changes in physical activity (training) and life-style factors.
technique were performed before and after catheter-balloon valvuloplasty. Left heart catheterization with a 7 French pigtail catheter was performed via the femoral approach. Left ventriculography was performed before and after catheter-balloon valvuloplasty. Catheter-balloon valvuloplasty was performed by the antegrade double balloon method. An 8 French transseptal sheath (USC1 Corporation, Billerica MA) was introduced into the left atrium. Through this, a 7 French end-hole balloon flotation catheter was advanced through the left ventricle to the descending aorta. This was exchanged for a double lumen catheter (Cordis Corporation, FL) and then two 0.035 inch exchange guidewires. The interatrial septum was first dilated (8 mm balloon) followed by the mitral valve - a combination of a 15 mm and a 20 mm balloon in 4 patients, and two 20 mm balloons in 3 patients (Mansfield Scientific, Watertown MA). Hemodynamic calculations
Materials
and Methods
Patient population
Right and left heart pressures were recorded, and mitral valve area was calculated [8] before and after catheter-balloon valvuloplasty.
The patient population consisted of 7 females, all in New York Heart Association class 2 or 3 for heart failure with predominant mitral stenosis by clinical evaluation. All patients were without other medical diseases and were entered consecutively into this study. Informed consent was obtained from all patients and the protocol was approved by the hospital’s ethics committee. At baseline, all were in normal sinus rhythm. Mild mitral regurgitation was present in 1 patient and minimal aortic regurgitation was present in 4. The remainder were without any other significant valvular regurgitation.
Two-dimensional and Doppler echocardiographic studies were performed with ATL MK600 (Seattle, WA) equipment. Mitral valve area was calculated by the pressure half-time method [9]. Values represent ‘the average obtained from several beats. For the detection of atria1 septal defect the sample volume was placed on the right atria1 side of the interatrial septum in the subcostal and parasternal right ventricular inflow tract views.
Catheterization and valvuloplasty protocol
Exercise tests
Right heart catheterization using a 7 French thermodilution catheter was performed via a transjugular or transfemoral approach. Multiple site oximetry for the measurement of atria1 septal defects and cardiac output by the thermodilution
Patients performed continuous incremental, maximal, treadmill exercise tests the day before and within 5 days after mitral valvuloplasty. The protocol was developed based on an energetic cost normogram in which the load increase in
Echo-Doppler studies
Y
each stage approached one MET (3.5 ml/kg/min of oxygen consumption). For this protocol modest increments in workload occur every 3 min [lo]. In the last 30 s of each stage the following variables were measured: (1) systolic and diastolic arterial pressure (mmHg); (2) heart rate (beats/ mitt) through the average of 10 R-R intervals on the electrocardiogram; (3) pulmonary ventilation in l/min of body temperature pressure saturated, obtained by the expired air collection in a Tissot gassometer (Collins, USA) through a low resistance respiratory mask (Vacumed, USA); (4) oxygen consumption and carbon dioxide production standard temperature pressure dry expressed in ml/kg/min, obtained by the respiratory method through the analysis of samples of the expired air in an M-11 oxygen analyzer and an LB-2 carbon dioxide (Beckman, USA). For each exercise test we determined the following. (1) Peak oxygen consumption, corresponding to the highest attained oxygen consumption in each test. (2) Ventilatory anaerobic threshold, determined by the ventilatory method [lo] from analysis of the relationships of pulmonary ventilation with oxygen consumption and carbon dioxide production. The level of oxygen consumption beyond which pulmonary ventilation increased out of proportion as compared to the
TABLE
Statistics Data were analyzed by the Wilcoxon method for unmatched pairs and by the paired Student r-test, when applicable [l I]. The significance level was fixed at 0.05 (5%). Results Echo-Doppler and hemodynamic measurements (Table 1) Mitral valvuloplasty led to increases in Doppler mitral valve area from 0.9 f 0.3 cm’ to 1.9 f 0.7 cm* (p < 0.02) and to increases in valve area calculated by the Gorlin formula from 0.9 k 0.3 to 1.8 k 0.6 cm2 (p < 0.001). Mitral valvuloplasty provoked reductions in mean left atria1 pressure (from 24 f 8 to 13 k 7 mmHg, p < 0.01) and in
1
Echo-Doppler
and hemodynamic Dp v.a.
Mean SD p value
oxygen consumption increase, without increase in the pulmonary ventilation and carbon dioxide production relationship, was taken as the ventilatory anaerobic threshold. (3) Ventilatory equivalent for oxygen, expressed as the quotient between pulmonary ventilation and oxygen consumption was determined in each stage of the protocol.
measurements LAP mean
PAP mean
C.O.
mean Grad
Gorlin v.a.
pre
post
pre
post
pre
post
pre
post
pre
post
pre
post
1.4 1.3 0.7 0.9 0.8 0.7 0.6
2.7 1.4 2.4 1.5 1.4 1.0 2.7
27 17 23 40 14 26 25
18 10 09 11 05 21 17
48 22 21 48 22 44 50
32 20 18 30 20 30 45
2.5 4.2 4.9 5.2 2.9 2.9 2.5
2.6 3.9 1.2 5.6 3.1 2.8 3.0
15 14 17 2x 13 20 18
10 04 OX 07 04 10 04
1.2 1.1 1.2 1.o 0.X 0.6 0.6
2.1 2.0 2.6 2.2 1.6 0.9 1.5
0.9 0.3
1.9 0.7 < 0.02
24 08
13 07 < 0.01
36 13
28 10 < 0.02
3.6 1.2
4.0 1.7 < 0.05
18 05
0.9 0.3
1.8 0.6 < 0.001
07 03 < 0.005
Dp v.a. = mitral valve area by echo-Doppler km’): LAP mean = left atria1 mean pressure (mmHg); PAP mean = mean pulmonary arterial pressure (mmHg); C.O. = cardiac output (I/mm); mean Grad = mean gradient between left atrium and end-diastolic left ventricular pressure (mmHg); Gorlin v.a. = mitral valve area calculated by Gorlin formula (cm’): pre = values pre valvuloplasty: post = values post valvuloplasty.
10 TABLE 2 Mean values and standard deviations for age, anthropometric mitral valvuloplasty.
Mean SD
Age
Weight
Height
(yr)
(kg)
Cm)
53 40 34 31 27 46 28 37 9.8
73.0 58.4 55.2 47.3 48.5 46.3 38.8 52.5 11.0
1.60 1.58 1.60 1.57 1.51 1.58 1.50 1.56 0.04
findings and cardiopulmonary
Number of stages
responses to exercise pre and post
Peak V02 (ml/kg/min)
AT VOz (ml/kg/min)
pre
post
pre
post
pre
post
4.0 4.0 5.0 4.0 4.0 5.0 3.0 4.1 0.7
5.0 5.0 6.0 6.0 6.0 7.0 4.0 5.6 1.0
11.39 14.87 17.62 19.49 16.43 16.17 13.17 15.59 2.72
12.13 17.02 19.07 20.55 16.22 20.51 12.81 16.90 3.44
8.24 12.23 10.93 16.19 13.36 13.36 10.42 12.10 2.55
8.38 14.98 11.72 15.03 13.76 14.74 9.75 12.62 2.71
Peak VO, = peak oxygen consumption; AT VO, = ventilator-y anaerobic threshold.
mean pulmonary artery pressure (from 36 f 1.3 to 28 & 10 mmHg, p < 0.02). No significant changes in cardiac output occurred with catheterballoon valvuloplasty (from 3.6 f 1.2 to 4.0 f 1.7 l/min>. In 2 patients, after catheter-balloon valvuloplasty, small atria1 septal defects were detected by the echo-Doppler technique that were not detected by oximetric measurements. Exercise tests Exercise tests were accomplished without complications in all patients before and after mitral valvuloplasty. After valvuloplasty all patients reached a higher maximal workload (Table 2). When comparing pre- and post-valvuloplasty measurements, there were no significant differences in mean values for heart rate or for systolic and diastolic blood pressures during the exercise protocol (Table 3).
As shown in Table 2, there was no significant increase in peak oxygen consumption when we compared pre- (15.59 + 2.72 ml/kg/min) and post- (16.90 _t 3.44 ml/kg/min) valvuloplasty values. Furthermore, there was no significant change in mean values of ventilatory anaerobic threshold when we compared pre- (12.10 & 2.55 ml/kg/ min) and post- (12.62 k 2.71 ml/kg/min) valvuloplasty exercise tests. Mean values of oxygen consumption were significantly higher in the first three stages of the exercise protocol when we compared pre- and post-valvuloplasty exercise tests (Table 4 and Fig. 1). Mean values of pulmonary ventilation were significantly higher in the first 3 stages of the exercise protocol when we compared pre- and post-valvuloplasty tests (Table 4 and Fig. 2). In Table 4 values corresponding to the fourth stage of the exercise protocol represent the mean of 6 patients, because 1 patient was unable to perform
TABLE 3 Mean values and standard deviations for heart rates and arterial blood pressure pre and post mitral valvuloplasty. No. of patients
Stage
7 7 7 6
1 2 3 4
Systolic arterial pressure (mmHg)
Heart rate (beats/min) Pre
Post
120.28 + 18.33 136.86 + 20.60 142.43 & 22.56 157.50 f 20.08
110.57 f 120.86 + 133.57 * 148.17 +
14.80 14.23 15.63 13.07
Pre
Post
122.85 & 21.38 117.14 f 24.97 112.85 f 20.58 114.17 f 24.17
115.71 + 112.85 f 114.28 i 118.33 f
Diastolic arterial pressure CmmHg) Pre
7.86 11.13 12.72 14.72
81.43 + 80.00 f 78.57 + 77.50 +
Post 8.99 10.00 6.90 9.87
72.86 4 72.86 + 77.14 t 79.16 +
4.87 4.88 7.56 6.63
11
16,
42
1 5-
41.
1 4.
40.
-&
39.
\p
3.3.
Y -m
37.
> ’
36. 35 34
7. 6 0
0
4
2
Stages
of
c z
15
y
10
Exercise
more than 3 stages before valvuloplasty. Mean values of VEO, were significantly higher in the last 3 stages of the protocol when we compared pre- and post-valvuloplasty tests (Table 4 and Fig. 3). Discussion The impact of percutaneous transvenous mitral valvuloplasty on exercise performance within 5 days of the procedure, was the main purpose of the present study. Our hemodynamic results were similar to those of previous reports [1,2]: a significant increase of mitral valve area together with a decrease of left atria1 pressure as well as a reduction of mean pulmonary artery pressure.
5
Ok
4
2 Stages
of
Exercise
Fig. 2. Pulmonary ventilation (VE) in 7 patients at stages 1, 2 and 3, and in 6 patients at stage 4; pre (0) and post (+ ) catheter-balloon valvuloplasty (CBV).
TABLE
of
Fig. 3. Ventilatory equivalent for 0, (VEO,) expressed as the quotient between pulmonary ventilation WE) and oxygen uptake 0’0,) in 7 patients at stages 1, 2 and 3. and in 6 patients at stage 4: pre ( q 1 and post ( + ) catheter-balloon valvuloplasty (CBV).
25
20
4
2
Stages
Exercise
Fig. 1. Oxygen uptake NO,) pre (0) and post (+) catheter(CBV) in 7 patients at stages 1, 2 and 3, balloon valvuloplasty and in 6 patients at stage 4 of the exercise treadmill protocol.
; .-
k
I
331
4
Mean values valvuloplasty.
and
No. of patients
Stage
7 7 7 b
1 2 3 4
standard
deviations
respiratory
VO, (ml/kg/min) Pre
VO, = minute
for
10.15 12.14 13.92 15.31
2.41 2.00 2.16 2.33
oxygen consumption:
during
cardiopulmonary
VE U/mitt)
7.68 9.84 12.29 14.14
f + f *
2.63 * 1.83 * 2.08 * 2.20
VE = minute
ventilation;
+ + + +
3.47 3.97 3.75 4.79
VEO,
testing
pre
and
post
mitral
14.45 16.94 20.62 24.91
= ventilatory
Post
Pre
Post
20.29 24.27 27.94 32.11
exercise
VEO>
Pre
Post f + f f
factors
f k k k
4.95 * 3.38 * 4.40 * 6.28 equivalent
40.31 39.49 39.70 39.53
i * + +
7.27 3.91 3.66 4.12
for oxygen:
38.13 34.94 34.00 34.04
* p < 0.05
+ 3.04 _t 3.28 * + 4.30 * + 4.84 *
12
After mitral valvuloplasty all patients exercised to a higher maximal workload beyond the ventilatory anaerobic threshold which occurred on average at 77.5 and 74.9% of peak oxygen consumption pre and post valvuloplasty, respectively. Peak oxygen consumption values pre and post mitral valvuloplasty were similar in spite of a marked reduction in resting left atria1 pressure. These findings led us to the assumption that the high left atria1 and pulmonary venous pressures of mitral stenosis do not limit peak oxygen uptake during exercise. Additionally, the finding of similar peak VO, values when comparing exercise tests performed before and soon after valvuloplasty, suggests that the observed changes in cardiopulmonary response were not due to a training effect. High values for oxygen uptake at lower workloads may be attributed to higher cost of breathing secondary to hyperventilation and to the reduced pulmonary compliance resulting from pulmonary venous hypertension observed in mitral stenosis [12]. The mean values for oxygen consumption and for pulmonary ventilation were significantly lower at the first three stages of the exercise protocol after mitral dilatation. The increased ventilatory response to exercise in patients with mitral stenosis has been attributed to enhanced chemical or chemoreceptor drive [13,14], to tachypnea secondary to decrease in lung compliance [15] and to pulmonary congestion leading to stimulation of juxtapulmonary capillary receptors [16]. After successful commissurotomy, exercise ventilation was significantly reduced [17]. Reduced exercise ventilation soon after valvuloplasty together with a reduced oxygen consumption in each stage of exercise may be explained by an attenuation of the aforementioned mechanisms. All of our patients were able to complete a greater number of stages of the exercise protocol after valvuloplasty. Exercise duration correlates well with severity of mitral stenosis, determined at cardiac catheterization [l&19], and could possibly be utilized as an independent method of assessing early results of mitral valvuloplasty. Maximal heart rate achieved at peak exercise was found to be reduced after commissurotomy [17].
There has been some evidence that partial correction of the excessive increase in plasma catecholamine levels during exercise in patients with severe mitral stenosis, is responsible for reducing heart rate response to exercise [20]. Furthermore, mitral dilatation improves the ability to fill the ventricle and therefore via the Frank-Starling mechanism generates a larger stroke volume lowering the heart rate. Although not significant, there was a reduction in mean heart rate of approximately 10 beats/min in our patients for each stage of the exercise protocol after mitral valvuloplasty. Perhaps a larger number of patients would make this difference statistically significant. Conclusions Percutaneous transvenous mitral commissurotomy significantly improves hemodynamic parameters. In this group of patients we observed an increase in exercise capacity with lower oxygen uptake and lower pulmonary ventilation without change in peak oxygen consumption. We speculate that for each stage of the protocol the cost of breathing was reduced and the oxygen consumed was more effectively utilized during exercise. Increases in peak VO, require time for peripheral factors, such as muscle capillary density and oxidative enzyme activity, to increase in response to physical conditioning consequent to changes in life-style after successful mitral valvuloplasty. References 1 Inoue K, Owaki T, Nakamura T, Kitamura F, Miyamoto N. Clinical application of transvenous mitral commissurotomy by a new balloon catheter. J Thoracic Cardiovasc Surg 1984;87:394-402. 2 Palacios IF, Block PC, Wilkins GT, Weyman AE. Followup of patients undergoing percutaneous mitral balloon valvotomy. Analysis of factors determining restenosis. Circulation 1989;79:573-579. 3 Levine MJ, Erny RE, Leonard BM et al. Long term follow-up in 105 patients undergoing percutaneous balloon mitral valvuloplasty. J Am Co11 Cardiol 1989;13:18A. 4 McKay CR, Kawanishi DT, Kitlewski A et al. Improvement in exercise capacity and exercise hemodynamics 3 months after double-balloon, catheter balloon valvuloplasty treatment of patients with symptomatic mitral stenosis Circulation 1988;77:1013-1021.
5 Tamai J, Nagata S, Akaike M, Ishikura F, Yamagishi M, Miyatake K. Improvement in exercise hemodynamics after balloon mitral valvuloplasty: non-invasive examination using continuous wave Doppler. Circulation 1988;78 (suppl II) 4. 6 Weber KT. Kinasewitz CT. Janick JS: Fishman AP. Oxygen utilization and ventilation during exercise in patients with chronic cardiac failure. Circulation 1982;65:121312.31. 7 McElroy PA, Janicki JS, Weber KT. Cardiopulmonary exercise testing congestive heart failure. Am J Cardiol I988;67:35A-40A. 8 Gorlin R. Sawyer CG. Haynes PW. Goodale WT. Dexter L. Effects of exercise on circulatory dynamics in mitral stenosis. III. Am Heart J 1951:41:192-203. 9 Hatle L, Angelsen B. In: Doppler ultrasound in cardiology. 2nd Ed., Philadelphia: Lea and Febiger, 1985;118-128. IO American College of Sports Medicine. Guidelines for exercise testing and prescription. Philadelphia: Lea and Fehiger, 1986:179 pp. I I Siegel. S. Estatista uno pariametnica para ciencias do comportamento. McGraw Hill, 1981;350 pp. 12 White HC, Butler J. Donald KW. Lung compliance in patients with mitral stenosis. Clin Sci 3958;17:667-679. I3 Donald KW. Gloster J, Harris EA, Reeves J, Harris P. The production of lactic acid during exercise in normal
14
I5
I6 17
I8
I9
30
subjects and in patients with rheumatic heart disease. Am Heart J 1961;62:494-519. Cotes JE. The role of oxygen, carbon dioxide and lactic acid in the ventilatory response to exercise in patients with mitral stenosis. Clin Sci 1955;14:317-328. Palmer WH, Gee JBL. Mills FC, Bates DB. Disturbances of pulmonary function in mitral valve disease. Can Med Assoc J 1963;89:744-750. Paintal AS. Mechanism of stimulation F type J pulmonary receptors. J Physiol 1969:203:511-532. Reid JW, Ablet M, Cotes JE. Ventilatory responses to exercise and to carbon dioxide in mitral stenosis before and after valvulotomy: causes of tachypnea. Clin Sci Mol Med 197854% 16. Almendral JM. Garcia. Andocin JM, Schanez-Cascos A. DeRabogo P. Treadmill stress testing in the evaluation of patients with valvular heart disease: possible role in the assessment of functional capacity and severity of the Iesion. Cardiology 1982;69:42-51. Vacek JL, Valentin-Stone P, Wolfe M. Davis WR. The value of standardized exercise testing in the noninvasive evaluation of mitral stenosis. Am J Med Sci 1986;292:335343. Ikeda J. Haneda T. Canada H et al. The degree of increment in plasm catecholamine in patients with mitral stenosis by mild exercise. Am Heart J 1987:l l3:1103-I 107.
