- Email: [email protected]
Immediate and Long-Term Follow-Up of Percutaneous Balloon Mitral Valvuloplasty in Pregnant Patients With Rheumatic Mitral Stenosis
Immediate and Long-Term Follow-Up of Percutaneous Balloon Mitral Valvuloplasty in Pregnant Patients With Rheumatic Mitral Stenosis Cesar A. Esteves, MD, PhDa, Juan S. Munoz, MDa, Sergio Braga, MD, PhDa, Januario Andrade, MD, PhDa, Zilda Meneghelo, MD, PhDa, Nisia Gomes, MDa, Mercedes Maldonado, MDa, Vinicius Esteves, MDa, Rodrigo Sepetiba, MD, PhDa, J. Eduardo Sousa, MD, PhDa, and Igor F. Palacios, MDb,* Percutaneous mitral balloon valvuloplasty (PMV) can be performed during pregnancy without significant maternal risk or fetal morbidity or mortality. However, little is known about long-term follow-up results after PMV in populations of pregnant women. Thus, the present study was undertaken to determine the immediate and long-term outcomes after PMV in a large cohort of pregnant patients with severe mitral stenosis. The patient population consisted of 71 consecutive pregnant women with severe rheumatic mitral stenosis admitted to the hospital with severe congestive heart failure (New York Heart Association class III and IV) for PMV. All patients underwent clinical and obstetric evaluations, electrocardiography, and 2-dimensional and Doppler echocardiography. PMV was successful in all patients, resulting in a significant increase in mitral valve area from 0.9 ⴞ 0.2 to 2.0 ⴞ 0.3 cm2 (p <0.001). At the end of pregnancy, 98% of the patients were in New York Heart Association functional class I or II. At a mean follow-up of 44 ⴞ 31 months, the total event-free survival rate was 54%. The mean gestational age at delivery time was 38 ⴞ 1 weeks. Preterm deliveries occurred in 9 patients (13%), including 2 twin pregnancies. The remaining 66 of 75 newborns (88%) had normal weight (mean 2.8 ⴞ 0.6 kg) at delivery. At long-term follow-up of 44 ⴞ 31 months after birth, the 66 children exhibited normal growth and development and did not show any clinical abnormalities. In conclusion, PMV is safe and effective, has a low morbidity and mortality rate for the mother and the fetus, and has favorable long-term results in pregnant women with rheumatic mitral stenosis in New York Heart Association functional class III or IV. © 2006 Elsevier Inc. All rights reserved. (Am J Cardiol 2006;98:812– 816)
Percutaneous mitral balloon valvuloplasty (PMV) has been established as an alternative to surgical mitral commissurotomy in the treatment of most patients with symptomatic rheumatic mitral stenosis.1–9 Previous reports have demonstrated that PMV can be performed safely during pregnancy in patients with severe mitral stenosis without significant maternal risk or fetal morbidity or mortality.10 –15 However, at the present time, there are few data on long-term follow-up results after PMV in larger patient populations of pregnant women.16,17 The aim of this study was to report immediate and long-term outcomes after PMV in a large cohort of pregnant patients with severe mitral stenosis. Methods Study population: The study population consisted of 71 consecutive pregnant women (mean age 27 ⫾ 6 years) with a Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil; and bMassachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Manuscript received December 23, 2005; revised manuscript received and accepted March 30, 2006. * Corresponding author: Tel: 617-726-8424; fax: 617-726-6800. E-mail address: [email protected] (I.F. Palacios).
0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2006.03.068
severe rheumatic mitral stenosis admitted with severe congestive heart failure (New York Heart Association [NYHA] functional class III or IV) to the Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil, from August 1989 to November 1997 for PMV. PMV was performed in pregnant women with mitral stenosis when they met the following criteria: (1) NYHA functional class III or IV, refractory to maximum medical therapy; (2) PMV is preferentially performed at a gestational age of ⱖ28 weeks (after the second trimester of pregnancy), because it can be performed irrespective of gestational age in the presence of unstable clinical conditions; and (3) echocardiographic findings of severe rheumatic mitral stenosis with favorable mitral valve anatomy for PMV. Patients with more than moderate mitral regurgitation (MR) at baseline, severe aortic or tricuspid valve disease that required surgery, recent thromboembolic stroke, acute infection processes, and the echocardiographically confirmed presence of left atrial thrombi were excluded. All patients underwent clinical and obstetric evaluations, electrocardiography, and 2-dimensional and Doppler echocardiography on the day of the procedure. The severity of www.AJConline.org
Valvular Heart Disease/PMV During Pregnancy
mitral stenosis was assessed before and after PMV using 2-dimensional and Doppler echocardiography. All patients included in this study provided written informed consent. PMV: PMV was performed in the fasting state in the catheterization laboratory. Twenty-four hours before the procedure, patients received indomethacin (100 mg twice a day rectally) in an effort to inhibit uterine contractions. To limit fetal radiation exposure, abdominal and pelvic lead shielding of patients was used, and contrast left ventriculography was not performed. The percutaneous treatment technique (the double-balloon technique or the Inoue technique) was chosen at the discretion of the operator. All PMV procedures were performed under local anesthesia using the transseptal, anterograde left-sided cardiac approach. The double-balloon and Inoue techniques were used in 44 patients (62%) and 27 patients (38%), respectively. A detailed description of the 2 PMV techniques has previously been reported.1–9 A successful optimal outcome was defined as a final post-PMV mitral valve area (MVA) of ⱖ1.5 cm2 or an increase in MVA of ⬎25% compared with the MVA before PMV in the absence of severe MR.2–9,18 After the procedure, patients were transferred to a general ward and monitored. Clinical, 2-dimensional, and Doppler echocardiographic studies were repeated 24 to 48 hours after PMV. Echocardiographic analysis: Two-dimensional and Doppler echocardiography was performed with an Advanced Technologies Laboratories system, Ultra-Mark 9 HDI (ATL, San Mateos, California) and Ultra-Mark 9 DigitalPlus, with a 3.0-MHz transducer. MVA, peak diastolic mitral gradient, mean diastolic mitral gradient, and the severity of MR were assessed before PMV, 24 to 48 hours afterward, and at long-term follow-up. Before the procedure, mitral valve morphology was assessed using Wilkins’s echocardiographic score criteria.19 MVA was estimated from the Doppler pressure halftime method and by planimetry. MR was graded as mild, moderate, or severe according to jet length and color flow mapping.20 Hemodynamic analysis: Right- and left-sided cardiac hemodynamic measurements (mean pulmonary artery pressure, mean left atrial pressure and end-diastolic left ventricular pressure, and cardiac output) were obtained before and immediately after PMV.1–9 Clinical follow-up: In-hospital adverse clinical events, including death, mitral valve surgery, pericardial tamponade, thromboembolic events, and complete heart block, were prospectively collected. Patients were followed clinically for a mean of 44 ⫾ 31 months (range 6 to 104) after PMV. The cardiology, obstetric, and pediatric departments of the Institute Dante Pazzanese of Cardiology performed the clinical evaluations. End points of follow-up were allcause mortality, mitral valve replacement or repair, repeat PMV, and clinical assessment according to NYHA functional classification of congestive heart failure. Additionally, the presence of echocardiographic restenosis (MVA
813
⬍1.5 cm2, associated with late loss ⬎50% of the index gain) was also determined.21–23 In addition, follow-up Kaplan-Meier event-free survival after PMV of this pregnant patient population was obtained and compared with a subpopulation of 108 patients from the Massachusetts General Hospital database matched by gender and age (27 ⫾ 6 vs 30 ⫾ 4 years, p ⫽ NS). Pediatricians assessed the children’s health, growth, and cognitive status development at birth, at 1 year after birth, and at a mean follow-up of 44 ⫾ 31 months simultaneously with the mothers’ clinical and echocardiographic examinations. Statistical analysis: All statistical analyses were performed with commercially available software (SPSS version 6.0, SPSS, Inc., Chicago, Illinois). Continuous variables are expressed as mean ⫾ 1 SD and categorical data as percentages. Comparisons between preprocedure, postprocedure, and follow-up measurements were performed with a 2-tailed Student’s paired t test. Categorical variables were compared using chi-square statistics. Correlation between gestational age (valvotomy time) and newborn weight was measured using Pearson’s test. Multiple stepwise logistic regression analyses of pre- and post-PMV MVA independent variables were performed to determine independent predictors of restenosis. Event-free survival curves were constructed by the Kaplan-Meier method, and survival probabilities were compared by the log-rank test. A p value of ⬍0.05 was considered significant. Results Patient population: The patient population included 71 patients with a mean age of 27 ⫾ 6.0 years and a mean gestational age of 24 ⫾ 7 weeks (range 6 to 34). Thirtythree of the 71 patients (52%) were in NYHA functional class IV, and the remaining 48% of patients were in NYHA functional class III. Forty-two (59.2%) patients underwent PMV during the third trimester of pregnancy, whereas 26 patients (36.6%) and 3 patients (4.2%) had the procedure performed in the second and first trimesters, respectively. Thirty-seven patients (52%) had Wilkins echocardiographic scores ⱕ8, and 34 patients (48%) had echocardiographic scores ⬎8. The mean echocardiographic score of the overall population was 8 ⫾ 1. All patients were in normal sinus rhythm, 3 (4.2%) had histories of previous surgical commissurotomy, and 2 (2.8%) had a previous PMV. Immediate outcome: PMV was successful in all patients, as evaluated by 2-dimensional echocardiography performed 48 hours after the procedure. Hemodynamic outcomes: PMV resulted in significant decreases in mean left atrial pressure (25.4 ⫾ 8.1 to 12.0 ⫾ 6.1 mm Hg, p ⬍0.001), mean diastolic mitral gradient (18.0 ⫾ 7.0 to 3.9 ⫾ 3.1 mm Hg, p ⬍0.01), and mean pulmonary artery pressure (38 ⫾ 15 to 24 ⫾ 11 mm Hg, p ⬍0.05). Echocardiographic outcomes: The mean MVA was 0.9 ⫾ 0.2 cm2 before PMV and increased to 2.0 ⫾ 0.3 cm2
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Figure 1. Changes in MR produced by PMV in 71 pregnant patients with severe mitral stenosis.
(p ⬍0.001) immediately after PMV. Follow-up echocardiograms were obtained for 65 of 71 patients (92%) at a mean follow-up of 43 ⫾ 32 months. At long-term follow-up, MVA had decreased significantly from 2.0 ⫾ 0.3 to 1.7 ⫾ 0.3 cm2 (p ⬍0.001). Peak and mean diastolic gradients had decreased significantly 48 hours after the procedure (p ⬍0.001) but remained very much unchanged at 43 ⫾ 32 month follow-up compared with postprocedure values (peak diastolic gradient 0.8 ⫾ 12.1 mm Hg, p ⫽ 0.4; mean diastolic gradient 1.7 ⫾ 10.6 mm Hg, p ⫽ 0.01). The echocardiographic restenosis rate was 14% (9 of 65 patients). Multiple stepwise logistic regression analysis failed to identify any independent predictor of restenosis. In-hospital follow-up: Thromboembolic events occurred in 2 patients (2.8%). One patient developed an acute arterial occlusion at the access site in the right femoral artery, which was resolved by surgery. Another patient had a transient ischemic attack without neurologic sequelae. The pre- and post-PMV incidence of MR are shown in Figure 1. Twenty patients (28%) had no MR before the procedure, 45 patients (63%) had mild MR, and 6 patients (8%) had moderate degrees of MR. At 48 hours after PMV, 4 patients (6%) remained without MR, 40 patients (56%) had developed mild MR, 23 patients (32%) had moderate MR, and 4 patients (5.6%) showed severe MR. In addition, echocardiographic evaluation detected left-to-right shunts at the atrial level after PMV in 6 patients (8%); however, none of them were hemodynamically significant because all had pulmonary/systemic flow ratios ⬍1.5:1. It was noteworthy that at the end of pregnancy, 98% of the patients were in NYHA functional class I or II. Mothers’ long-term clinical follow-up: Long-term follow-up information was available in 65 of 71 of the total patient population (92%). Two patients had partial clinical follow-up obtained at 12 and 27 months after PMV. There was only 1 death (1.4%), which occurred secondary to hepatitis. Hepatitis occurred as a consequence of blood transfusion requirement after mitral valve replacement 48 months after PMV. At long-term follow-up, severe MR was present in 3 of 65 patients (4.6%), and they were treated with surgical mitral valve repair. Only 1 of the 4 patients
Figure 2. Event-free survival Kaplan-Meier curve (survival with freedom from mitral valve surgery and repeat PMV).
Figure 3. Comparison of event-free survival Kaplan-Meier curves (survival with freedom from mitral valve surgery and repeat PMV) from the pregnant patient population (dashed line) and those from 108 patients with a comparable mean age (30 ⫾ 4 years) from the Massachusetts General Hospital PMV database (solid line).
with severe MR immediately after PMV had severe MR at long-term follow-up; 3 of the 4 patients with severe MR immediately after PMV had significant improvement of MR by echocardiographic analysis at follow-up. Furthermore, there was a decrease or disappearance of MR in 23 patients (35%). Of the 9 patients with echocardiographic restenosis, 2 symptomatic patients underwent surgical mitral valve repair, 4 symptomatic patients underwent repeat PMV, and 3 asymptomatic patients were treated medically. A combined event (death, mitral valve replacement or repair, and repeat PMV) occurred in 9 of 63 patients (14.3%) with complete clinical follow-up. Of the remaining 54 patients (86%) who were free of combined events, 53 (98%) were in NYHA class I or II, and 1 patient was in NYHA class IV. Furthermore, at a mean follow-up of 44 ⫾ 39 months, the total event-free survival rate was 54% (Figure 2). As shown in Figure 3, the long-term follow-up event-free survival of our pregnant patients was similar to that of an age- and gender-matched cohort of 108 patients from the Massachusetts General Hospital PMV database. Moreover, the overall restenosis-free rate was 70% at 87 months after PMV, and
Valvular Heart Disease/PMV During Pregnancy
90% of the patients were free of surgical mitral valve repair at 48-month follow-up. Offspring follow-up: The mean gestational age at the time of delivery of the 71 patients who underwent PMV was 38.0 ⫾ 1.2 weeks. Of the 71 patients who underwent PMV in the present study, 2 (2.8%) were lost to follow-up and 1 (1.4%) had a spontaneous abortion. Seventy-one patients who underwent PMV delivered a total 75 newborns. Twelve patients (17%) had spontaneous vaginal delivery, whereas 54 (76%) underwent cesarean sections. Of the group with spontaneous vaginal delivery, 1 patient delivered a stillborn infant. In contrast, of the 54 cesarean patients, 1 delivered a stillborn infant and 4 (7.4%) gave birth to twins (2 delivered prematurely, of whom 1 patient had fetal death, and the other 2 patients reached term). The incidence of preterm deliveries was 13% (9 patients), including 2 twin pregnancies. The remaining 66 newborns (88%) had normal weight (mean 2.8 ⫾ 0.6 kg) immediately after delivery. At a mean long-term follow-up of 44 ⫾ 31 months (median 48), the 66 children exhibited normal growth and development and did not show any clinical abnormalities. No correlation was found between gestational age (at the time of PMV) and newborn weight (r ⫽ ⫺0.07, p ⫽ 0.3). Discussion The present study demonstrates that PMV is a safe and effective therapeutic procedure for pregnant patients with heart failure secondary to severe rheumatic mitral stenosis. In agreement with data from previous reports of PMV performed during pregnancy,10 –15 the present study showed a high clinical success rate of PMV, which resulted in 98% of the patients being in NYHA functional class I or II at the end of pregnancy. Only 1 death, unrelated to the procedure, had occurred at 48-month follow-up. Two patients (2.8%) had peripheral embolic events, but there were no other severe complications, such as cardiac perforation, tamponade, or complete atrioventricular block. Our findings show that, at the present time, PMV should be considered as the first management therapeutic choice for pregnant patients with symptomatic mitral stenosis refractory to optimal medical treatment. The procedure should also be considered for those patients who require prolonged hospitalization, as well as for those who need large amounts of drugs to maintain a compensated clinical state. In this latter group, PMV should be considered to avoid the potential harmful effects of cardiovascular drugs, such as the teratogenic effect, depression of the uterine flow, premature birth, and even interference in the dynamics of labor.22,23 Mitral stenosis is often diagnosed during a pregnancy when a previously asymptomatic woman presents with advanced congestive heart failure. With rest, diuretics, and -blocker use, 73% of those patients improve in NYHA functional class (from class III or IV to class I or II). Although surgically closed mitral valve commissurotomy carries a lower risk to the mother, it is associated with
815
a fetal mortality rate of 6% to 17%.24 –26 Furthermore, with open surgical commissurotomy performed under general anesthesia and extracorporeal circulation, fetal mortality reaches 33%.25,26 PMV can be performed whenever possible, starting from the 12th week of gestation, to avoid the inherent risks of radiation (organogenesis). However, in the presence of unstable clinical conditions, PMV can be performed irrespective of gestational age. Successful PMV during pregnancy should improve the patient’s clinical condition, permitting a pregnant woman to return to NYHA functional class I or II as a consequence of improved hemodynamics and MVA. PMV should permit gestation to reach full term, offering the fetus good conditions for adequate intrauterine development and better clinical conditions to the mother until and during delivery. In the present study, this principal objective was reached in 99% of the patients (NYHA functional class I or II) at the moment of delivery. The long-term event-free survival of our pregnant PMV population is similar to that in an age- and gender-matched cohort of 108 patients (mean age of 30 ⫾ 4 years) from the Massachusetts General Hospital database. In conclusion, our study further supports the impression that PMV is the procedure of choice to treat pregnant women with rheumatic mitral stenosis in NYHA functional class III or IV and/or unresponsive to adequate medical treatment. In this population, PMV is a safe and effective treatment that results in excellent immediate and long-term outcomes for mothers and their offspring. 1. Inoue K, Owaki T, Nakamura T, Miyamoto N. Clinical application of intravenous mitral commissurotomy by a new balloon catheter. J Thorac Cardiovasc Surg 1984;87:394 – 402. 2. Cheng TO, Holmes DR Jr. Percutaneous balloon mitral valvuloplasty by the Inoue balloon technique: the procedure of choice for treatment of mitral stenosis. Am J Cardiol 1998;81:624 – 628. 3. Palacios I, Block PC, Brandi S, Blanco P, Casal H, Pulido JI, Munoz S, D’Empaire G, Ortega MA, Jacobs M, Vlahakes G. Percutaneous balloon valvotomy for patients with severe mitral stenosis. Circulation 1987;75:778 –784. 4. Hung JS, Chern MS, Wu JJ, Fu M, Yeh KH, Wu YC, Chern WJ, Chua S, Lee CB. Short and long-term results of catheter balloon percutaneous transvenous mitral commissurotomy. Am J Cardiol 1991;67:854 – 862. 5. Dean LS, Mickel M, Bonan R, Holmes DR Jr, O’Neill WW, Palacios IF, Rahimtoola S, Slater JN, Davis K, Kennedy JW. Four-year follow-up of patients undergoing percutaneous balloon mitral commissurotomy: a report from the National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry. J Am Coll Cardiol 1996;28:1452– 1457. 6. Hernandez R, Banuelos C, Alfonso F, Goicolea J, Fernandez-Ortiz A, Escaned J, Azcona L, Almeira C, Macaya C. Long-term clinical and echocardiographic follow-up after percutaneous mitral valvuloplasty with the Inoue balloon. Circulation 1999;99:1580 –1586. 7. Palacios IF, Tuzcu ME, Weyman AE, Newell JB, Block PC. Clinical follow-up of patients undergoing percutaneous mitral balloon valvotomy. Circulation 1995;92:671– 676. 8. Palacios IF, Sanchez P, Harrell LC, Weyman AE, Block PC. Which patients benefit from percutaneous mitral balloon valvuloplasty? Prevalvuloplasty and postvalvuloplasty variables that predict long-term outcome. Circulation 2002;105:1465–1471.
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9. Turi ZG, Reyes VP, Raju BS, Raju AR, Kumar DN, Rajagopal P, Sathyanarayana PV, Rao DP, Srinath K, Peters P. Percutaneous balloon versus surgical closed commissurotomy for mitral stenosis. A prospective, randomized trial. Circulation 1991;83:1179 –1785. 10. Palacios IF, Block PC, Wilkins GT, Rediker DE, Dagget WM. Percutaneous mitral balloon valvotomy during pregnancy in a patient with severe mitral stenosis. Cathet Cardiovasc Diagn 1988;15:109 –111. 11. Smith R, Brender B, McCredie M. Percutaneous transluminal balloon dilatation of the mitral valve in pregnancy. Br Heart J 1989;61:551–553. 12. Mangione JA, Zuliani MFM, Del Castilho JM, Noguiera EA, Arie S. Percutaneous double balloon mitral valvotomy in pregnant women. Am J Cardiol 1989;64:99 –102. 13. Esteves CA, Ramos AIO, Braga SLN, Harrison JK, Sousa JEMR. Effectiveness of percutaneous balloon mitral valvotomy during pregnancy. Am J Cardiol 1991;68:930 –934. 14. Ben Farhat M, Gamra H, Betbout F, Maatouk J, Jarror M, Addad F, Tiss M, Hammami S, Chahbani I, Thaalbi R. Percutaneous balloon mitral commissurotomy during pregnancy. Heart 1997;77:564 –567. 15. Cheng TO. Percutaneous Inoue balloon valvuloplasty is the procedure of choice for symptomatic mitral stenosis in pregnant women. Cathet Cardiovasc Intervent 2000;50:418. 16. Mangione JA, Lourenco RM, dos Santos ES, Shigueyuki A, Mauro MF, Cristovao SA, Del Castillo JM, Siqueira EJ, Bayerl DM, Lins Neto OB, Selman AA. Long-term follow-up of pregnant women after percutaneous mitral valvuloplasty. Cathet Cardiovasc Intervent 2000; 50:413– 417. 17. Nercolini DC, Bueno RRL, Guerios E, Tarastchuck JC, Kubrusly LF. Percutaneous mitral balloon valvuloplasty in pregnant women with mitral stenosis. Cathet Cardiovasc Intervent 2002;57:318 –322.
18. Abascal VM, Wilkins GT, O’Shea JP, Choong CY, Palacios IF, Thomas JD, Rosas E, Newell JB, Block PC, Weyman AE. Prediction of successful outcomes in 130 patients undergoing percutaneous balloon mitral valvotomy. Circulation 1990;82:448 – 456. 19. Wilkins GT, Weyman AE, Abascal VM, Block PC, Palacios IF. Percutaneous balloon dilation of the mitral valve: an analysis of echocardiographic variables related to outcome and the mechanism of dilatation. Br Heart J 1988;60:299 –308. 20. Helmcke F, Nanda NC, Hsiung MC, Soto B, Adey CK, Goyal RG, Gatewood RP. Color Doppler assessment of mitral regurgitation with orthogonal planes. Circulation 1987;75:175–183. 21. Palacios IF, Block PC, Wilkins GT, Weyman AE. Follow-up of patients undergoing percutaneous balloon mitral valvotomy—analysis of factors determining restenosis. Circulation 1989;79:573–579. 22. Avila WS, Grinberg M. Gestacao em portadoras de afeccoes cardiovasculares. Experiencia com 1000 casos. Ar Qbras Cardiol 1993;60: 5–11. 23. Souza JAM, Martinez EE Jr, Ambrose JA, Alves CMR, Born D, Buffolo E, Carvalho ACC. Percutaneous balloon mitral valvuloplasty in comparison with open mitral valve commissurotomy for mitral stenosis during pregnancy. J Am Coll Cardiol 2001;37:900 – 903. 24. Knapp RC, Arditi LI. Closed mitral valvulotomy in pregnancy. Clin Obstet Gynecol 1968;11:978 –991. 25. Schenker JG, Polishuk WZ. Mitral valvotomy during pregnancy. Surg Gynecol Obstet 1968;127:593–597. 26. Vosloo S, Reichart B. The feasibility of closed mitral valvotomy in pregnancy. J Thorac Cardiovasc Surg 1987;93:675– 679.
Percutaneous mitral balloon valvuloplasty (PMV) has been established as an alternative to surgical mitral commissurotomy in the treatment of most patients with symptomatic rheumatic mitral stenosis.1–9 Previous reports have demonstrated that PMV can be performed safely during pregnancy in patients with severe mitral stenosis without significant maternal risk or fetal morbidity or mortality.10 –15 However, at the present time, there are few data on long-term follow-up results after PMV in larger patient populations of pregnant women.16,17 The aim of this study was to report immediate and long-term outcomes after PMV in a large cohort of pregnant patients with severe mitral stenosis. Methods Study population: The study population consisted of 71 consecutive pregnant women (mean age 27 ⫾ 6 years) with a Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil; and bMassachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. Manuscript received December 23, 2005; revised manuscript received and accepted March 30, 2006. * Corresponding author: Tel: 617-726-8424; fax: 617-726-6800. E-mail address: [email protected] (I.F. Palacios).
0002-9149/06/$ – see front matter © 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2006.03.068
severe rheumatic mitral stenosis admitted with severe congestive heart failure (New York Heart Association [NYHA] functional class III or IV) to the Institute Dante Pazzanese of Cardiology, Sao Paulo, Brazil, from August 1989 to November 1997 for PMV. PMV was performed in pregnant women with mitral stenosis when they met the following criteria: (1) NYHA functional class III or IV, refractory to maximum medical therapy; (2) PMV is preferentially performed at a gestational age of ⱖ28 weeks (after the second trimester of pregnancy), because it can be performed irrespective of gestational age in the presence of unstable clinical conditions; and (3) echocardiographic findings of severe rheumatic mitral stenosis with favorable mitral valve anatomy for PMV. Patients with more than moderate mitral regurgitation (MR) at baseline, severe aortic or tricuspid valve disease that required surgery, recent thromboembolic stroke, acute infection processes, and the echocardiographically confirmed presence of left atrial thrombi were excluded. All patients underwent clinical and obstetric evaluations, electrocardiography, and 2-dimensional and Doppler echocardiography on the day of the procedure. The severity of www.AJConline.org
Valvular Heart Disease/PMV During Pregnancy
mitral stenosis was assessed before and after PMV using 2-dimensional and Doppler echocardiography. All patients included in this study provided written informed consent. PMV: PMV was performed in the fasting state in the catheterization laboratory. Twenty-four hours before the procedure, patients received indomethacin (100 mg twice a day rectally) in an effort to inhibit uterine contractions. To limit fetal radiation exposure, abdominal and pelvic lead shielding of patients was used, and contrast left ventriculography was not performed. The percutaneous treatment technique (the double-balloon technique or the Inoue technique) was chosen at the discretion of the operator. All PMV procedures were performed under local anesthesia using the transseptal, anterograde left-sided cardiac approach. The double-balloon and Inoue techniques were used in 44 patients (62%) and 27 patients (38%), respectively. A detailed description of the 2 PMV techniques has previously been reported.1–9 A successful optimal outcome was defined as a final post-PMV mitral valve area (MVA) of ⱖ1.5 cm2 or an increase in MVA of ⬎25% compared with the MVA before PMV in the absence of severe MR.2–9,18 After the procedure, patients were transferred to a general ward and monitored. Clinical, 2-dimensional, and Doppler echocardiographic studies were repeated 24 to 48 hours after PMV. Echocardiographic analysis: Two-dimensional and Doppler echocardiography was performed with an Advanced Technologies Laboratories system, Ultra-Mark 9 HDI (ATL, San Mateos, California) and Ultra-Mark 9 DigitalPlus, with a 3.0-MHz transducer. MVA, peak diastolic mitral gradient, mean diastolic mitral gradient, and the severity of MR were assessed before PMV, 24 to 48 hours afterward, and at long-term follow-up. Before the procedure, mitral valve morphology was assessed using Wilkins’s echocardiographic score criteria.19 MVA was estimated from the Doppler pressure halftime method and by planimetry. MR was graded as mild, moderate, or severe according to jet length and color flow mapping.20 Hemodynamic analysis: Right- and left-sided cardiac hemodynamic measurements (mean pulmonary artery pressure, mean left atrial pressure and end-diastolic left ventricular pressure, and cardiac output) were obtained before and immediately after PMV.1–9 Clinical follow-up: In-hospital adverse clinical events, including death, mitral valve surgery, pericardial tamponade, thromboembolic events, and complete heart block, were prospectively collected. Patients were followed clinically for a mean of 44 ⫾ 31 months (range 6 to 104) after PMV. The cardiology, obstetric, and pediatric departments of the Institute Dante Pazzanese of Cardiology performed the clinical evaluations. End points of follow-up were allcause mortality, mitral valve replacement or repair, repeat PMV, and clinical assessment according to NYHA functional classification of congestive heart failure. Additionally, the presence of echocardiographic restenosis (MVA
813
⬍1.5 cm2, associated with late loss ⬎50% of the index gain) was also determined.21–23 In addition, follow-up Kaplan-Meier event-free survival after PMV of this pregnant patient population was obtained and compared with a subpopulation of 108 patients from the Massachusetts General Hospital database matched by gender and age (27 ⫾ 6 vs 30 ⫾ 4 years, p ⫽ NS). Pediatricians assessed the children’s health, growth, and cognitive status development at birth, at 1 year after birth, and at a mean follow-up of 44 ⫾ 31 months simultaneously with the mothers’ clinical and echocardiographic examinations. Statistical analysis: All statistical analyses were performed with commercially available software (SPSS version 6.0, SPSS, Inc., Chicago, Illinois). Continuous variables are expressed as mean ⫾ 1 SD and categorical data as percentages. Comparisons between preprocedure, postprocedure, and follow-up measurements were performed with a 2-tailed Student’s paired t test. Categorical variables were compared using chi-square statistics. Correlation between gestational age (valvotomy time) and newborn weight was measured using Pearson’s test. Multiple stepwise logistic regression analyses of pre- and post-PMV MVA independent variables were performed to determine independent predictors of restenosis. Event-free survival curves were constructed by the Kaplan-Meier method, and survival probabilities were compared by the log-rank test. A p value of ⬍0.05 was considered significant. Results Patient population: The patient population included 71 patients with a mean age of 27 ⫾ 6.0 years and a mean gestational age of 24 ⫾ 7 weeks (range 6 to 34). Thirtythree of the 71 patients (52%) were in NYHA functional class IV, and the remaining 48% of patients were in NYHA functional class III. Forty-two (59.2%) patients underwent PMV during the third trimester of pregnancy, whereas 26 patients (36.6%) and 3 patients (4.2%) had the procedure performed in the second and first trimesters, respectively. Thirty-seven patients (52%) had Wilkins echocardiographic scores ⱕ8, and 34 patients (48%) had echocardiographic scores ⬎8. The mean echocardiographic score of the overall population was 8 ⫾ 1. All patients were in normal sinus rhythm, 3 (4.2%) had histories of previous surgical commissurotomy, and 2 (2.8%) had a previous PMV. Immediate outcome: PMV was successful in all patients, as evaluated by 2-dimensional echocardiography performed 48 hours after the procedure. Hemodynamic outcomes: PMV resulted in significant decreases in mean left atrial pressure (25.4 ⫾ 8.1 to 12.0 ⫾ 6.1 mm Hg, p ⬍0.001), mean diastolic mitral gradient (18.0 ⫾ 7.0 to 3.9 ⫾ 3.1 mm Hg, p ⬍0.01), and mean pulmonary artery pressure (38 ⫾ 15 to 24 ⫾ 11 mm Hg, p ⬍0.05). Echocardiographic outcomes: The mean MVA was 0.9 ⫾ 0.2 cm2 before PMV and increased to 2.0 ⫾ 0.3 cm2
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Figure 1. Changes in MR produced by PMV in 71 pregnant patients with severe mitral stenosis.
(p ⬍0.001) immediately after PMV. Follow-up echocardiograms were obtained for 65 of 71 patients (92%) at a mean follow-up of 43 ⫾ 32 months. At long-term follow-up, MVA had decreased significantly from 2.0 ⫾ 0.3 to 1.7 ⫾ 0.3 cm2 (p ⬍0.001). Peak and mean diastolic gradients had decreased significantly 48 hours after the procedure (p ⬍0.001) but remained very much unchanged at 43 ⫾ 32 month follow-up compared with postprocedure values (peak diastolic gradient 0.8 ⫾ 12.1 mm Hg, p ⫽ 0.4; mean diastolic gradient 1.7 ⫾ 10.6 mm Hg, p ⫽ 0.01). The echocardiographic restenosis rate was 14% (9 of 65 patients). Multiple stepwise logistic regression analysis failed to identify any independent predictor of restenosis. In-hospital follow-up: Thromboembolic events occurred in 2 patients (2.8%). One patient developed an acute arterial occlusion at the access site in the right femoral artery, which was resolved by surgery. Another patient had a transient ischemic attack without neurologic sequelae. The pre- and post-PMV incidence of MR are shown in Figure 1. Twenty patients (28%) had no MR before the procedure, 45 patients (63%) had mild MR, and 6 patients (8%) had moderate degrees of MR. At 48 hours after PMV, 4 patients (6%) remained without MR, 40 patients (56%) had developed mild MR, 23 patients (32%) had moderate MR, and 4 patients (5.6%) showed severe MR. In addition, echocardiographic evaluation detected left-to-right shunts at the atrial level after PMV in 6 patients (8%); however, none of them were hemodynamically significant because all had pulmonary/systemic flow ratios ⬍1.5:1. It was noteworthy that at the end of pregnancy, 98% of the patients were in NYHA functional class I or II. Mothers’ long-term clinical follow-up: Long-term follow-up information was available in 65 of 71 of the total patient population (92%). Two patients had partial clinical follow-up obtained at 12 and 27 months after PMV. There was only 1 death (1.4%), which occurred secondary to hepatitis. Hepatitis occurred as a consequence of blood transfusion requirement after mitral valve replacement 48 months after PMV. At long-term follow-up, severe MR was present in 3 of 65 patients (4.6%), and they were treated with surgical mitral valve repair. Only 1 of the 4 patients
Figure 2. Event-free survival Kaplan-Meier curve (survival with freedom from mitral valve surgery and repeat PMV).
Figure 3. Comparison of event-free survival Kaplan-Meier curves (survival with freedom from mitral valve surgery and repeat PMV) from the pregnant patient population (dashed line) and those from 108 patients with a comparable mean age (30 ⫾ 4 years) from the Massachusetts General Hospital PMV database (solid line).
with severe MR immediately after PMV had severe MR at long-term follow-up; 3 of the 4 patients with severe MR immediately after PMV had significant improvement of MR by echocardiographic analysis at follow-up. Furthermore, there was a decrease or disappearance of MR in 23 patients (35%). Of the 9 patients with echocardiographic restenosis, 2 symptomatic patients underwent surgical mitral valve repair, 4 symptomatic patients underwent repeat PMV, and 3 asymptomatic patients were treated medically. A combined event (death, mitral valve replacement or repair, and repeat PMV) occurred in 9 of 63 patients (14.3%) with complete clinical follow-up. Of the remaining 54 patients (86%) who were free of combined events, 53 (98%) were in NYHA class I or II, and 1 patient was in NYHA class IV. Furthermore, at a mean follow-up of 44 ⫾ 39 months, the total event-free survival rate was 54% (Figure 2). As shown in Figure 3, the long-term follow-up event-free survival of our pregnant patients was similar to that of an age- and gender-matched cohort of 108 patients from the Massachusetts General Hospital PMV database. Moreover, the overall restenosis-free rate was 70% at 87 months after PMV, and
Valvular Heart Disease/PMV During Pregnancy
90% of the patients were free of surgical mitral valve repair at 48-month follow-up. Offspring follow-up: The mean gestational age at the time of delivery of the 71 patients who underwent PMV was 38.0 ⫾ 1.2 weeks. Of the 71 patients who underwent PMV in the present study, 2 (2.8%) were lost to follow-up and 1 (1.4%) had a spontaneous abortion. Seventy-one patients who underwent PMV delivered a total 75 newborns. Twelve patients (17%) had spontaneous vaginal delivery, whereas 54 (76%) underwent cesarean sections. Of the group with spontaneous vaginal delivery, 1 patient delivered a stillborn infant. In contrast, of the 54 cesarean patients, 1 delivered a stillborn infant and 4 (7.4%) gave birth to twins (2 delivered prematurely, of whom 1 patient had fetal death, and the other 2 patients reached term). The incidence of preterm deliveries was 13% (9 patients), including 2 twin pregnancies. The remaining 66 newborns (88%) had normal weight (mean 2.8 ⫾ 0.6 kg) immediately after delivery. At a mean long-term follow-up of 44 ⫾ 31 months (median 48), the 66 children exhibited normal growth and development and did not show any clinical abnormalities. No correlation was found between gestational age (at the time of PMV) and newborn weight (r ⫽ ⫺0.07, p ⫽ 0.3). Discussion The present study demonstrates that PMV is a safe and effective therapeutic procedure for pregnant patients with heart failure secondary to severe rheumatic mitral stenosis. In agreement with data from previous reports of PMV performed during pregnancy,10 –15 the present study showed a high clinical success rate of PMV, which resulted in 98% of the patients being in NYHA functional class I or II at the end of pregnancy. Only 1 death, unrelated to the procedure, had occurred at 48-month follow-up. Two patients (2.8%) had peripheral embolic events, but there were no other severe complications, such as cardiac perforation, tamponade, or complete atrioventricular block. Our findings show that, at the present time, PMV should be considered as the first management therapeutic choice for pregnant patients with symptomatic mitral stenosis refractory to optimal medical treatment. The procedure should also be considered for those patients who require prolonged hospitalization, as well as for those who need large amounts of drugs to maintain a compensated clinical state. In this latter group, PMV should be considered to avoid the potential harmful effects of cardiovascular drugs, such as the teratogenic effect, depression of the uterine flow, premature birth, and even interference in the dynamics of labor.22,23 Mitral stenosis is often diagnosed during a pregnancy when a previously asymptomatic woman presents with advanced congestive heart failure. With rest, diuretics, and -blocker use, 73% of those patients improve in NYHA functional class (from class III or IV to class I or II). Although surgically closed mitral valve commissurotomy carries a lower risk to the mother, it is associated with
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a fetal mortality rate of 6% to 17%.24 –26 Furthermore, with open surgical commissurotomy performed under general anesthesia and extracorporeal circulation, fetal mortality reaches 33%.25,26 PMV can be performed whenever possible, starting from the 12th week of gestation, to avoid the inherent risks of radiation (organogenesis). However, in the presence of unstable clinical conditions, PMV can be performed irrespective of gestational age. Successful PMV during pregnancy should improve the patient’s clinical condition, permitting a pregnant woman to return to NYHA functional class I or II as a consequence of improved hemodynamics and MVA. PMV should permit gestation to reach full term, offering the fetus good conditions for adequate intrauterine development and better clinical conditions to the mother until and during delivery. In the present study, this principal objective was reached in 99% of the patients (NYHA functional class I or II) at the moment of delivery. The long-term event-free survival of our pregnant PMV population is similar to that in an age- and gender-matched cohort of 108 patients (mean age of 30 ⫾ 4 years) from the Massachusetts General Hospital database. In conclusion, our study further supports the impression that PMV is the procedure of choice to treat pregnant women with rheumatic mitral stenosis in NYHA functional class III or IV and/or unresponsive to adequate medical treatment. In this population, PMV is a safe and effective treatment that results in excellent immediate and long-term outcomes for mothers and their offspring. 1. Inoue K, Owaki T, Nakamura T, Miyamoto N. Clinical application of intravenous mitral commissurotomy by a new balloon catheter. J Thorac Cardiovasc Surg 1984;87:394 – 402. 2. Cheng TO, Holmes DR Jr. Percutaneous balloon mitral valvuloplasty by the Inoue balloon technique: the procedure of choice for treatment of mitral stenosis. Am J Cardiol 1998;81:624 – 628. 3. Palacios I, Block PC, Brandi S, Blanco P, Casal H, Pulido JI, Munoz S, D’Empaire G, Ortega MA, Jacobs M, Vlahakes G. Percutaneous balloon valvotomy for patients with severe mitral stenosis. Circulation 1987;75:778 –784. 4. Hung JS, Chern MS, Wu JJ, Fu M, Yeh KH, Wu YC, Chern WJ, Chua S, Lee CB. Short and long-term results of catheter balloon percutaneous transvenous mitral commissurotomy. Am J Cardiol 1991;67:854 – 862. 5. Dean LS, Mickel M, Bonan R, Holmes DR Jr, O’Neill WW, Palacios IF, Rahimtoola S, Slater JN, Davis K, Kennedy JW. Four-year follow-up of patients undergoing percutaneous balloon mitral commissurotomy: a report from the National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry. J Am Coll Cardiol 1996;28:1452– 1457. 6. Hernandez R, Banuelos C, Alfonso F, Goicolea J, Fernandez-Ortiz A, Escaned J, Azcona L, Almeira C, Macaya C. Long-term clinical and echocardiographic follow-up after percutaneous mitral valvuloplasty with the Inoue balloon. Circulation 1999;99:1580 –1586. 7. Palacios IF, Tuzcu ME, Weyman AE, Newell JB, Block PC. Clinical follow-up of patients undergoing percutaneous mitral balloon valvotomy. Circulation 1995;92:671– 676. 8. Palacios IF, Sanchez P, Harrell LC, Weyman AE, Block PC. Which patients benefit from percutaneous mitral balloon valvuloplasty? Prevalvuloplasty and postvalvuloplasty variables that predict long-term outcome. Circulation 2002;105:1465–1471.
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