European Heart Journal (1992) 13, 1658-1664

Percutaneous balloon mitral valvuloplasty in eight pregnant women with severe mitral stenosis M. BEN FARHAT, F. MAATOUK, F. BETBOUT, M. AYARI, H. BRAHIM*, M. SOUISSI*, K. SGHAIRI AND H. GAMRA

KEY WORDS: Mitral stenosis, mitral valvuloplasty, pregnancy, therapeutic catherization.

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The Catheterization and Cardiovascular Diagnosis Unit and the *Obstetrics and Gynecology Unit, Fattouma Bourguiba University Hospital, 5000 Monaslir, Tunisia

Normal gestation is associated with a hyperdynamic adaptive state. The circulatory changes represent an additional burden on the cardiovascular system of women with rheumatic mitral stenosis (MS). Life-threatening complications can occur in pregnant women with severe MS. We successfully performed percutaneous balloon mitral valvotomy (PMV) in eight pregnant patients (mean age 28 ±6-9 years, range 21-38 years). Pregnancy mean age was 24-6 ±6-5 weeks. Five patients were in NYHA functional class III and three patients were in class IV. Emergency PMV seemed to be life saving to both mother andfoetus in one case. All patients but one had pliable valves. PMV was achieved using the double balloon transseptal technique. To protect the foetus from radiation, the patient's pelvic-abdominal area was shielded and left ventriculography was not performed. The total mean time of PM V was 72 ±19 min and that offluoroscopy was 16-6 ±7-8 min. Gorlin's mitral valve area increased from 0-83±015 to 2-4±0-34 cm2 and the cardiac index from 31 ±0-77 to 4-2 ±0-791. min~'. m~2. Left atrium pressure decreased from 29 ±10 to 14 ±5 mmHg and mitral valve gradient from 21 ±7 to 6 ±3 mmHg. There were no complications or residual MS. A t a mean follow-up of 13-2 ± 9-4 months, all patients were in NYHA class I and had a normal course of pregnancy. The eight women delivered healthyfull-term babies. At 1—25 months post-partum follow-up, the eight infants had shown normal growth and development. PMV can be the treatment of choice for the management ofpregnant women with severe MS and disability. Introduction Normal pregnancy is associated with a hyperdynamic circulatory state including an increase in blood volume, heart rate and stroke volume and a decrease in systemic vascular resistance resulting in a 40% rise of cardiac output"^11. The presence of severe mitral stenosis (MS) may impair a pregnant women's ability to tolerate these haemodynamic adjustments. Moreover, the increased blood volume and tachycardia alter the left atrial emptying and can lead to a significant rise in the venocapillary pulmonary pressure. Life-threatening complications, peripartum pulmonary oedema in particular, can occur1'561. Despite intensive medical therapy, disabling symptoms usually persist and have, in the past, required cardiac surgery17"12'. However, mitral commissurotomy and valve replacement during gestation both carry a serious risk for mother and foetus. Recently, percutaneous mitral balloon valvotomy (PMV) has been a safe alternative to surgery in non-pregnant'13"251 and pregnant patients'26"31'. This report describes the successful use of PMV in eight consecutive pregnant patients with severe MS and very disabling symptoms, and emphasizes the reversibility of circulatory abnormalities in pregnancy. Patients and methods PATIENTS (TABLE 1)

patients who had severe rheumatic MS. Eight of them were pregnant women (3%) (mean age 28 ±6-9 years, range 21-38 years). Time into pregnancy varied from 18 to 37 weeks (mean 24-6 ±6-5 weeks). Three women were pregnant for the first time and MS was discovered at their first visit to the clinic when they denied dyspnoea. A history of rheumatic fever was present in six patients. All patients were in sinus rythm. Five patients were in NYHA functional class III and three in class IV. The three auscultatory features of MS (i.e. prominent opening snap, diastolic rumble and loud first heart sound) were present in all patients but one. No patient had murmurs of concomitent mitral regurgitation or aortic valve disease. Patient 3 had mild tricuspid insufficiency. Despite optimum medical therapy including frusemide and digitalis the women's condition worsened. Only patient 6 was treated with /?-blockers (atenolol 3 x 50 mg per day). Patient 3 was in acute respiratory distress and showed marked wasting; 12 h after her admission she had uterus pain and contractions but the os remained closed and emergency PMV seemed to be life saving for both mother and foetus. At abdominal, physical, and echographic examination, uterine enlargement and foetus development were normal in all cases except patient 6 who presented a full-term pregnancy and had a hypotrophic foetus. One year earlier, patient 1 and patient 2 had an echographic mitral valve area of 1 -6 and 1 -5 cm2 respectively.

Between December 1987 and February 1992 we performed PMV in our laboratory in 272 consecutive Submitted for publication 6 April 1992. Correspondence M. Ben Farhat, MD, The Catheterization and Cardiovascular Diagnosis Unit, Fattouma Bourguiba University Hospital, 5000 Monastir, Tunisia. 0I95-668X/92I21658 + 07SO8.00 0


Two-dimensional pulsed and continuous wave Doppler echocardiographic examinations were performed 24 h before and after PMV. The Honeywell Ultra © 1992 The European Society of Cardiology

Mitral valvuloplasty in pregnant women 1659


Figure I Two-dimensional echocardiographic parasternal shortaxis view of the maximal mitral opening in early diastole in patient 1. A = planimetered M VA before at 0-77 cm2 (top) and 24 h after PM V at 2-7 cm2 (bottom). The cleavage along the two commissures has occurred.

Informed consent was obtained from the eight patients and their husbands. During the procedure, the patients pelvic abdominal area was shielded in order to protect the foetus from radiation. To minimize radiation exposure, left ventriculography was not performed. Fluoroscopy was used only when mandatory. PMV was performed after fasting state and premedication (20 mg of intravenous clorazepate) and after the administration of a local anaesthetic. Right and left-sided cardiac catheterization was performed from the left groin. Trans-septal catheterization was accomplished from the right femoral vein using a Brockenbrough needle, an 8 Fr Mullins sheath (USCI) and a dilator. The sheath was inserted into the left ventricle apex by a floating balloon catheter (7 Fr Critikon), after withdrawal of the dilator. Two long 0038-inch diameter exchange guidewires (USCI) were placed in the apex. Heparin was given (') after trans-septal catheterization. The sheath was then withdrawn and the inter-atrial septum was dilated using an 8 mm peripheral angioplasty balloon (USCI). Two pigtail valvulotomy balloon catheters (Mansfield Scientific Co.) were advanced and positioned across the mitral valve. Two balloons (18 and 20 mm in diameter respectively) were then simultaneously inflated by hand until the 'waist' disappeared. Results (Table 2)

Imager system was used in this study. Standard 2-D echo images were obtained in the parasternal long- and shortaxis views and the apical four-chambers and twochambers long-axis views. Special attention was taken to

Table 1


PMV was successful in the eight cases without any complications. The duration of the procedure varied from 54 min in patient 7 to 100 min in patients 2 and 6 (mean

Clinical and echocardiographic data

Age (years)


3$ 22

ii 31 26 is 24

Gestation number

Gestation time (weeks)

Functional class

24 30 18 18 20 37 24 26


2DMVA(cm 2 )

Doppler MVA (cm2)





0-77 105 0-70 1-00 110 0-72 0-7 I

2-7 2 21 2-3 2-9 2-4 21 2-3

0-84 1 0-7 0-80 1 0-65 0-8 0-9

2-6 19 2-2 2-2 31 2-4 21 2-2

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image entirely the subvalvular apparatus and to scan carefully the left atrium and its appendage to detect thrombus. Echographic mitral valve area (EMVA) was determined by planimetry of the mitral orifice in a 2-D short-axis view early in diastole (Figs 1 and 2) and by the transmitral pressure half-time method (Figs 2 and 3). MS was severe in all patients (EMVA < 11 cm2). No patient had a left atrium thrombus. Seven patients had pliable valves with mild or absent subvalvular disease (echocardiographic score < 8/16), and patient 2 had severely thickened mitral valves and extensive subvalvular disease.

1660 M. Ben Farhat et al.

72±19min). The total time of fluoroscopy was 16-6±78min (range 7-26 min). An impressive haemodynamic improvement was achieved in all patients (Table 2). Left atrium pressure decreased from 29±10 to 14±5mmHg and the mitral valve gradient decreased from 21 ± 7 to 6 ± 3 mmHg. Fig. 4 illustrates the dramatic decrease in LA and mean diastolic mitral gradient pressures post-PM V in patient 3. The cardiac index, which was as low as 1-51 .min" 1 . m" 2 in patient 6 (treated with atenolol), increased from 31 ±0-77 to 4-2±0-791.min-'.m- 2 . Gorlin's MVA increased from 0-83 ± 0 1 5 to 2-4±0-34 cm2 without residual stenosis. Arteriolar and total pulmonary vascular resistances and systemic vascular resistances improved as a consequence. Oximetry runs showed evidence of a trivial interatrial shunt in patient 7 with a pulmonary to systemic blood flow ratio of 1 -2. Two-dimensional and continuous wave doppler echocardiograms confirmed a substantial increase in MVA from 0-85 ± 0-13 to 2-36 ± 0-38 cm2. Fig. 1 depicts short-axis views early in diastole in patient 1 (MVA increased from 0-77 to 2-7 cm2) and Fig. 3 shows the mitral orifice in patient 2 pre- and post-PMV (MVA increased from 1 to 2 cm2). Fig. 2 (patient 1) and Fig. 3 (patient 2) are examples of continuous-wave Doppler recordings pre- and post-PMV and show a clearcut decrease in pressure half time after PMV. Each woman experienced a favourable improvement in symptoms of pulmonary congestion; digitalis and diuretics were discontinued. Seven patients were discharged from hospital on the fourth day following PMV. The early clinical course was complicated in patient 3: uterus cramps persisted over 36 h despite the intravenous use of terbutaline sulfate, a drug which acts upon uterus

P-2 receptors and stimulates uterine relaxation, but the cervical os remained closed. Five days following PMV this patient showed evidence of rheumatic fever recurrence. She was given acetylsalicylic acid (50 mg. kg" 1 . day"1) and she clinically recovered. She was discharged 3 weeks after PMV. POST-VALVULOPLASTY COURSE

At follow-up at 11-4±9-2 months (range 1-27 months), seven patients were in NYHA functional class I and patient 2 was in functional class II. The eight women had had a spontaneous vaginal delivery at full term assisted with forceps. The eight babies were healthy without any evidence of foetal abnormalities caused by radiation. Patient 6 who had a severe long-term untreated MS and PMV at full term delivered a moderately hypotrophic boy. At 1-25 months post-partum follow-up, the eight infants showed normal growth and development. Discussion

Normal pregnancy affects the maternal cardiovascular system and is associated with many adaptive circulatory changes. There is a 50% elevation of total blood volume concerning both the plasma and red cell components, a 30-50% increase in cardiac output due to increase in both stroke volume and heart rate, a decrease in peripheral vascular resistance resulting in a moderate reduction in systemic pressures (greater for diastolic than for systolic pressure)11"3' and an increase in ejection fraction and mean velocity of left ventricular circumferential fibre shorteningf4J. As a rule, these adjustments begin during the first trimester, reach a peak at about the 24th week of gestation

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Figure 2 Diastolic continuous-wave Doppler recordings and M-mode echocardiograms (right panel) in patient 1. Pre-PM V (top) = pressure half time 260 ms (A-B lines), M VA 0-84 cm1; EF slope 15 mm . s-'. Post-PMV (bottom) pressure half time 80 ms; MVA 2-7 cm2; EF slope 37 mm . s '.

Mitral valvuloplasty in pregnant women 1661

and are maintained until delivery. During labour, a further 20% increase in cardiac output can occur during uterine contractions'1"3'. These haemodynamic burdens, generally well tolerated by most normal women, may adversely affect women with significant heart disease, and can threaten both the mother and foetus1' •5~6'. In Tunisia, as in other developing countries, rheumatic valvular heart disease (particularly mitral stenosis) is still the most frequent abnormality in women of child-bearing age. Moreover, as suggested by other investigators'1-21, pregnancy may accelerate the stenotic process of the mitral orifice as in patients 1 and 2 and predispose to rheumatic fever recurrence as in patient 3. The presence of severe MS may impair a pregnant woman's ability to generate the increased cardiac output necessary to support gestation. It is noteworthy that in all patients reported here, the CI failed to increase despite a significant rise in LA pressure. In patients 3 and 6, CI was dramatically low before PMV and reduction in systemic

vascular resistance failed to occur. Thus, it is not surprising that pregnant patients with critical MS experience a worsening of their symptoms"-5-61. Maternal and fetal mortality varies directly with NYHA functional class, with a mortality rate of 0-4% in class I or II, increasing to 6-8% for women in class III or jyti.51 " j ^ ] a b o u r a n c j delivery periods represent the highest risk. PMV resulted in substantial haemodynamic improvement in all eight patients. Pregnant women with severe MS and disabling symptoms of pulmonary congestion despite intensive medical therapy need mechanical relief of their mitral obstruction. This was achieved more often in the past by surgical closed commissurotomy than by the open technique17""1. During closed surgical mitral commissurotomy maternal mortality was less than 3%(7"101. However, foetal mortality was as high as 13%. The prematurity rate was also high, reaching 37% in one study*8'. Higher maternal mortality of 5% and foetal mortality exceeding 30% have been reported with open

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Figure 3 Short-axis view and diastolic flow of mitral valve in patient 2 pre- (top) and post- (bottom) PMV. MVA increased from 1 to 2 cm2: A and B lines indicate the time (C = interval at which the peak gradient had decreased by 50% (220 and 110 ms respectively).

7662 M. Ben Farhat et al.

Table 2

Catheterizalion data pre- and immediately post-percutaneous mitral balloon valvotomy


PAP d m MGP s











102 6 27 52 28 39 20 94 55 68 4 0-9 775 487 150

73 5 12 28 13 20 3 90 50 64 4-4 2-7 670 227 91

112 7 31 48 30 38 24 110 62 85 3-7 1 990 406 13

115 6 14 34 16 22 11 110 62 85 4-9 19 853 224 75

110 10 45 90 50 70 33 100 70 84 2-7 0-6 1493 1244 497

107 10 12 75 40 55 5 98 70 83 3-7 2-2 957 721 564

74 7 31 50 28 37 20 105 70 90 3-3 0-9 1328 592 96

72 10 19 42 22 33 9 102 65 87 4-8 2-3 832 356 151

Patient 5


PAP d m MGP s



Patient 4

Patient 7

Patient 6

Patient 8









74 7 27 50 28 37 20 105 70 90 3-3 09 1328 592 96

70 10 19 42 22 33 9 102 65 85 4-8 2-3 832 356 151

62 3 8 25 10 18 6 90 60 75 1-5 0-7 2215 553 307

63 2 6 25 10 18 2 95 62 78 2-6 2-5 1451 342 228

80 11 35 86 43 54 25 92 61 73 3-3 0-7 884 830 296

81 3 20 50 29 38 4 90 58 68 3-8 2-1 804 515 244

112 4 26 35 16 24 21 106 77 92 2-7 1 1637 446 37

110 2 11 24 13 18 9 115 80 94 4-6 2-4 986 197 65

HR = heart rate (beats . mm '), pressures (P, mmHg), RA = right atrium, LA = left atrium, PA = pulmonary artery, Ao = Aorta, s = systolic, d = diastolic, m = mean, MGP =• mitral gradient pressure, CI = cardiac index (I min ' . m 2), MVA = mitral valve area (cm2), R = resistance (dynes s 'cm '), SVR = systemic vascular resistance, TPVR = total pulmonary vascular resistance, APVR = arteriolar pulmonary vascular resistance.

mitral surgery and cardiopulmonary bypass17"1. In a recent haemodynamic study performed in non-pregnant subjects we were somewhat disappointed by the closed commissurotomy results'121. Thus, PMV represented an attractive alternative to surgical commissurotomy for pregnant women with severe MS. We were also encouraged by the first 102 PMV results of our laboratory (patient 1 had PMV number 103). Since the initial description of PMV by K. Inoue et a/.'131 in 1984, this technique has been demonstrated to be successful in large studies of patients with symptomatic MS'14"251. Previous experience with PMV during pregnancy is limited to 17 patients'26"3'1. Our eight patients' results are similar to thefindingsof those previous reports. Moreover, PMV was accomplished as an emergency in one case and seemed to be life saving for both mother and foetus. There were neither immediate complications nor abortion. In previous studies and this

one, PMV was performed at different stages of pregnancy but always after the end of the first trimester, a time at which organogenesis of the foetus is achieved. All patients reported a marked symptomatic improvement and no further heart failure. Fluoroscopic radiation exposure carries a potential (albeit small) risk to the unborn child. However, the risk is diminished by appropriate pelvic lead shielding, a short radiation exposure time and avoidance of direct abdominal exposure. The total radiation dose was estimated at 0-2 rads in one study1261 and 005 rads in another1301. This dose is far below the maximum radiation which is recommended for therapeutic abortion'321. All women (15 patients) but two delivered healthy, full-term babies without any abnormalities related to radiation. One patient with a history of obstetric problems delivered a 32-week premature baby who died 1 month later of pneumonia; prematurity was not related to PMV or

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Patient 3

Patient 2

Patient 1

Mitral valvuloplasty in pregnant women 1663

100 mm Hg

Figure 4 Simultaneous left ventricular and left atrial pressures preand post-PMV in patient 3. A marked decrease in LA and mitral gradient pressures is shown.

radiation'281. Another woman delivered a normal baby at the end of the eighth month'301. Short-term follow-up of the 13 infants has shown normal growth and development'26"311. Although the long-term consequences to the child cannot be determined with certainty, abnormalities are unlikely to occur in childhood. Conclusion

Percutaneous mitral double balloon valvotomy is a safe and effective alternative to surgical commissurotomy in the management of severe mitral stenosis during pregnancy when symptoms are refractory to intensive medical therapy. We thank Sabah Mzilem, Jamila Rassas and Zohra Daly for their secretarial assistance and Najet Harzallah and Mahmoud Belkhouja for their technical assistance.

References [1] Perloff JK. Pregnancy and cardiovascular disease. In: Braunwald E, ed. Heart Disease. A Textbook of Cardiovascular Medicine, 2ndedn. Philadelphia: W. B. Saunders 1984; 1763-81. [2] Metcalfe J, Ueland K. Maternal cardiovascular adjustments to pregnancy. Prog Cardiovasc Dis 1974; 16: 363-74. [3] Katz R, Karliner JS, Resnik R. Effects of a natural volume overload state (pregnancy) on left ventricular performance in normal human subjects. Circulation 1978; 58:434-41. [4] Rubier S, Damani PM, Pinto ER. Cardiac size and performance during pregnancy estimated with echocardiography. Am J Cardiol 1977; 40: 534-8. [5] Szekely P, Turner R, Snaith L. Pregnancy and the changing pattern of rheumatic heart disease. Br Heart J 1973; 35: 1293-303. [6] Sugishita Y, Ito I, Ozeki K, Ohta C, Kubo T. Intracardiac pressures in pregnant patients with mitral stenosis. Jpn Heart J 1981; 22: 885-94. [7] Szekely P, Snaith L. The place of cardiac surgery in the management of the pregnant women with heart disease. J Obstet Gynecol 1963; 70: 69-77.

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[8] Knapp RC, Ardin LI. Closed mitral valvulotomy in pregnancy. Clin Obstet Gynecol 1968; 11:978-91. [9] El-Maraghy M, Abou Senna I, El-Tehewy F, Bassiouni M, Ayoub A, El-Sayed H. Mitral valvotomy in pregnancy. Am J Obstet Gynecol 1983; 145: 708-10. [10] Vosloo S, Reichart B. The feasibility of closed mitral valvotomy in pregnancy. J Thorac Cardiovasc Surg 1987; 93: 675-9. [11] Zitnik RS, Braundenburg RO, Sheldon R, Wallace RB. Pregnancy and open heart surgery. Circulation 1969; 39: 1257-62. [12] Ben Farhat M, Boussadia H, Ganddjbakhch I, Mzali H, Chouaieb A, Ayari M. Closed versus open mitral commissurotomy in pure noncalcific mitral stenosis: Hemodynamic studies before and after operation. J Thorac Cardiovasc Surg 1990; 99: 639-44. [13] Inoue K, Owaki T, Nakamura T, Kitamura F, Miyamoto N. Clinical application of transvenous mitral commissurotomy by a new balloon catheter. J Thorac Cardiovasc Surg 1984; 87: 394-402. [14] Zaibag MA, Kassab SA, Ribeiro PA, Fagjh MR. Percutaneous double balloon mitral valvotomy for rheumatic mitral valve stenosis. Lancet 1986; 1: 757-61. [15] Palacios IF, Block PC, Brandi S et al. Percutaneous balloon valvotomy for patients with severe mitral stenosis. Circulation 1987; 75: 778-84. [16] Babic UU, Pejcic P, Djurisic Z, Vucinic M, Grujicic SM. Percutaneous transarterial balloon valvuloplasty for mitral valve stenosis. Am J Cardiol 1986; 57: 1101-4. [17] Vahanian A, Michel PL, Cormier B et al. Results of percutaneous mitral commissurotomy in 200 patients. Am J Cardiol 1989; 63: 847-52. [18] Palacios IF, Block PC, Wilkins GT, Weyman AE. Follow-up of patients undergoing percutaneous mitral balloon valvotomy. Analysis of factors determining restenosis. Circulation 1989; 79: 573-9. [19] Nobuyoshi M, Hamasaki N, Kimura T el al. Indications, complications, and short-term clinical outcome of percutaneous transvenous mitral commissurotomy. Circulation 1989; 80: 782-92. [20] Ruiz CE, Allen WA and Lau FYK. Percutaneous double balloon valvotomy for severe rheumatic mitral stenosis. Am J Cardiol 1990; 65: 473-7. [21] Chen CR, Huang ZD, Lo ZX, Cheng TO. Comparison of single rubber-nylon balloon and double polyethylene balloon valvuloplasty in 94 patients with rheumatic mitral stenosis. Am Heart J 1990; 119: 102-11. [22] Berland J, Rocha P, Lefebure T et al. Percutaneous mitral valvotomy. Twin-At catheter in double balloon technique. Circulation (Abstr.) 1991; 84(Suppl. II): 724. [23] Lefevre T, Bonan R, Serra A el al. Resultats immediate et suivi a moyen terme apres valvuloplastie mitrale percutanee. Arch Mai Coeur 1991; 84: 1311-9. [24] Hung JS, Chern MS, Wu JJ el al. Short and long term results of catheter balloon percutaneous transvenous mitral commissurotomy. Am J Cardiol 1991; 67: 854-62. [25] Bassand JP, Schiele F, Bernard Y et al. The double-balloon and Inoue techniques in percutaneous mitral valvuloplasty: comparative results in a series of 232 cases. J Am Coll Cardiol 1991; 18:982-9. [26] Safian R, Berman A, Sachs B et al. Percutaneous balloon mitral valvuloplasty in a pregnant women with mitral stenosis. Cathet Cardiovasc Diagn 1988; 15: 103-8. [27] Palacios I, Block P, Wilkins G, Rediker D, Dagget W. Percutaneous mitral balloon valvotomy during pregnancy in a patient with severe mitral stenosis. Cathet Cardiovasc Diagn 1988; 15: 109-11. [28] Mangione JA, Zuliani MF, Del Castillo JM, Nogueira EA, Arie S. Percutaneous double balloon mitral valvuloplasty in pregnant women. Am J Cardiol 1989; 64:99-102. [29] Smith R, Brender D, Credie M. Percutaneous transluminal balloon dilatation of the mitral valve in pregnancy. Br Heart J 1989; 61: 551-3.

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[30] Drobinski G, Fraboulet P, MontalescotGf/a/. Valvuloplastie mitrale au quatrieme mois de grossesse. Protection foetale par un manteau de plomb. Arch MalCoeur 1991, 84: 249-51. [31] Esteves CA, Braga SN, Mattos LA el al. Mitral valvuloplasty during pregnancy. Circulation (Abstr.) 1990; 82 (Suppl. Ill): II, 498.

[32] DekabanAS Abnormalities in children, exposed to X-radiation during various stages of gestation: tentative timetable or radiation injury to the human fetus. Part I. J Nucl Med 968; 471-7

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Percutaneous balloon mitral valvuloplasty in eight pregnant women with severe mitral stenosis.

Normal gestation is associated with a hyperdynamic adaptive state. The circulatory changes represent an additional burden on the cardiovascular system...
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