Effect of Elevated Pulmonary Vascular Resistance on Outcomes AfterPercutaneous Mitral Valvuloplasty

Ignacio Cruz-Gonzalez, MD, PhDa,b,*, Marc J. Semigram, MDa, Ignacio Inglessis-Azuaje, MDa,Maria Sanchez-Ledesma, MDa,b, Javier Martin-Moreiras, MDb, Hani Jneid, MDc,Pablo Rengifo-Moreno, MDa, Roberto J. Cubeddu, MDd, Andrew O. Maree, MDe,

Pedro L. Sanchez, MD, PhDf, and Igor F. Palacios, MDa

Patients with mitral stenosis with severe pulmonary hypertension constitute a high-risk

aCardiologyMedical School, BHospital of SalamCollege of MediCenter, Houston,Florida; eCardioloIreland; and fCardMadrid, Spain. Mareceived and acce

See page 583*Correspondin

0008.E-mail addres

0002-9149/13/$ -http://dx.doi.org/1

subset for surgical commissurotomy or valve replacement. The aim of the present study wasto examine the effect of elevated pulmonary vascular resistance (PVR) on percutaneousmitral valvuloplasty (PMV) procedural success, short- and long-term clinical outcomes (i.e.,mortality, mitral valve surgery, and redo PMV) in 926 patients. Of the 926 patients, 263(28.4%) had PVR ‡4 Woods units (WU) and 663 (71.6%) had PVR <4 WU. Patients withPVR ‡4 WU were older and more symptomatic and had worse valve morphology for PMV.The patients with PVR ‡4 WU also had lower PMV procedural success than those withPVR <4 WU (78.2% vs 85.6%, p [ 0.006). However, after multivariate adjustment, PVRwas no longer an independent predictor of PMV success nor an independent predictor ofthe combined end point at a median follow-up of 3.2 years. In conclusion, elevated PVR atPMV is not an independent predictor of procedural success or long-term outcomes.Therefore, appropriately selected patients with rheumatic mitral stenosis might benefit fromPMV, even in the presence of elevated preprocedural PVR. � 2013 Elsevier Inc. All rightsreserved. (Am J Cardiol 2013;112:580e584)

Patients with mitral stenosis and severe pulmonaryhypertension (PH) have a poor prognosis. Mortality amongmedically treated patients has been reported to be 48% at1 year.1 Furthermore, PH has been considered a risk factor forpoor outcomes in patients undergoing mitral valve replace-ment. In some studies, operative mortality has ranged from15% to 31%1,2; however, other studies did not find an influ-ence of PH on mortality.3,4 More recently, several reportshave demonstrated improved outcomes in patients with PHundergoing mitral valve replacement. However, the peri-procedural mortality has still ranged from 2.3% to 10%.5,6

Percutaneous mitral valvuloplasty (PMV) has been recom-mended in selected patients with moderate or severe mitralstenosis who are symptomatic.7,8 Previous longitudinalstudies have confirmed that PMV in selected patients is a safeandwell-tolerated procedure that is associated with short- andlong-term benefits.9 However, the efficacy of PMV in patientswith severe PH has not been fully elucidated, specificallywithregard to the long-term outcomes. The present study was,

Division, Massachusetts General Hospital, Harvardoston, Massachusetts; bCardiology Division, Universityanca, Salamanca, Spain; cCardiology Division, Baylorcine, Michael E. DeBakey Veterans Affairs MedicalTexas; dAventura Hospital and Medical Center, Miami,gy Division, Waterford Regional Hospital, Waterford,iology Division, Gregorio Marañón University Hospital,nuscript received February 21, 2013; revised manuscriptpted April 3, 2013.for disclosure information.g author: Tel: (þ34) 68-742-5695; fax: (þ34) 92-327-

s: cruzgonzalez.ignacio@gmail.com (I. Cruz-Gonzalez).

see front matter � 2013 Elsevier Inc. All rights reserved.0.1016/j.amjcard.2013.04.022

therefore, designed to examine the effect of elevated pulmo-nary vascular resistance ([PVR] �4 Woods units [WU]) andPH on PMV procedural success and the short- and long-termclinical outcomes in patients with mitral stenosis.

Methods

Datawere collected prospectively for 926 patientswho hadundergone PMV at the Massachusetts General Hospital(Boston, Massachusetts). The study subjects were dividedinto 2 groups: patients with PVR �4 WU (320 dyne$s/cm5)and those with PVR <4 WU. We also performed an extraanalysis, dividing the population according a mean pulmo-nary artery pressure of�25mmHgat rest, as assessed by rightheart catheterization. All participants provided informedconsent, and the institutional review board approved the studyprotocol.

PMV was performed using a transseptal antegrade tech-nique, as previously described.10 Both double-balloon andInoue techniques were used. PVR was calculated as follows:(mean pulmonary artery pressure�mean pulmonary capillarywedge pressure)/cardiac index. The cardiac output was deter-minedby thermodilution in all cases,when feasible. If evidenceof left-to-right shunting was found or significant tricuspidregurgitation (TR) was present, the cardiac output was calcu-lated according to the assumed Fick principle (oxygenconsumption was estimated as 125 ml oxygen/min/m2). Themitral valve area was calculated using the Gorlin formula and2-dimensional echocardiographic planimetry.

The demographic and clinical variables, including age,gender, body surface area, New York Heart Associationfunctional class at presentation, presence of atrial fibrillation,and previous surgical commissurotomy or PMV, were

www.ajconline.org

Table 1Baseline characteristics stratified pulmonary vascular resistance (PVR)severity

Variable PVR (WU) p Value

<4 (n ¼ 663) �4 (n ¼ 263)

Female gender (%) 80.4 87.5 0.011Age (yrs) 53.4 � 14.9 59.8 � 15.58 0.001Atrial fibrillation (%) 44.5 58.4 0.001NYHA class (%) 0.001IeII 32.3 14.4IIIeIV 67.7 85.6

Fluoroscopic calcium grade (%) 0.0010e1 77.4 61.1�2 22.6 38.9

Echocardiographic score (%) 0.001�8 73.4 53.8>8 26.6 46.2

Tricuspid regurgitation �3 (%) 4.5 11.9 0.001Previous commissurotomy (%) 15.4 17.5 0.43

Data are presented as mean � SD or %.NYHA ¼ New York Heart Association.

Table 2Hemodynamic findings and procedure success stratified by pulmonaryvascular resistance (PVR) severity

Variable PVR (WU) p Value

<4 �4

CO (L/min)Before PMV 4.2 � 1.07 3.4 � 0.9 <0.001After PMV 4.7 � 1.25 4.04 � 1.14 <0.001

MG (mm Hg)Before PVM 13.62 � 5.68 15.02 � 5.81 <0.001After PMV 5.4 � 2.7 6.25 � 3.0 <0.001

MVA (cm2)Before PMV 0.98 � 0.27 0.78 � 0.25 <0.001After PMV 1.96 � 0.66 1.63 � 0.61 <0.001

PA (mm Hg)Before PMV 31.29 � 8.7 49.17 � 13.59 <0.001After PMV 26.30 � 8.27 38.24 � 12.55 <0.001

Post-PMV MR grade �3þ (%) 8 10 0.31PMV success* (%) 85.6 78.2 0.006

Data are presented as mean � SD or %.CO ¼ cardiac output; MG ¼ transmitral gradient; MR ¼ mitral regur-

gitation; MVA ¼ mitral valve area; PA ¼ pulmonary artery pressure.* Procedural success was defined as MR <3 and MVA �1.5 cm2 or

a 50% increase in MVA.

Table 3In-hospital complications grouped by pulmonary vascular resistance (PVR)severity

Variable PVR (WU) p Value

<4 �4

Death (in hospital)Not procedure related 3 (0.5) 7 (2.7) 0.003Procedure related 3 (0.5) 3 (1) 0.241Total 6 (0.9) 10 (3.8) 0.002

Tamponade 3 (0.5) 3 (1) 0.241Mitral valve replacementIn-hospital (total) 21 (3.2) 8 (3) 0.91Emergent 8 (1.2) 4 (1.5) 0.70

Atrioventricular block 4 (0.6) 1 (0.4) 0.67Stroke 11 (1.7) 3 (1.1) 0.55

Data are presented as n (%).

Valvular Heart Disease/Mitral Valvuloplasty and Pulmonary Hypertension 581

recorded. Additional variables collected included the echo-cardiographic score,11 pre- and post-PMV degree of mitralregurgitation, and the presence of fluoroscopically visiblemitral valve calcification (score 0 to 4).12 TR before PMVwas qualitatively assessed from none to severe using echo-cardiography. The echocardiographic studies were performedin the standard manner, and the TR grade was estimatedby integrating the continuous wave Doppler signal and colorflow mapping.13 The procedural variables included theinterventional technique (double balloon vs Inoue), effectiveballoon dilating area to body surface area, and pre- and post-PMV hemodynamic values (mean pulmonary artery and leftatrial pressures, mean mitral valve pressure gradient, meanpulmonary artery pressure, PVR, cardiac output, and calcu-lated mitral valve area). Procedure-related complicationsincluded death, mitral valve surgery, pericardial tamponade,stroke, and post-PMV mitral regurgitation �3. Procedure-related death was defined as in-hospital mortality directlyrelated to PMV. Successful PMV was defined as a post-PMVmitral valve area of�1.5 cm2 or a 50% increase in valve areawith post-PMV mitral regurgitation <3.14

The prespecified outcomes, including mortality, mitralvalve surgery (mitral valve replacement), and redo PMV,were recorded at follow-up. A combine end point, includingmortality, mitral valve replacement, and redo PMV, wasdefined, and each component of the combine end point wasanalyzed separately.

Continuous and categorical variables are expressed as themean � SD and percentages, respectively. The follow-uptime is reported as the median and interquartile range.Student’ t test and the chi-square test, or Fisher exact test whennecessary, were used to compare the continuous and cate-gorical variables, respectively. Multivariate logistic regres-sion analyses were performed to determine whether anelevated PVR and mean pulmonary pressure were indepen-dently associated with PMV success (including the covariatesgender, age, echocardiographic score, mitral valve area beforePMV, mitral regurgitation before PMV, and previous

comissurotomy8). Kaplan-Meier estimates were used todetermine the total survival and event-free survival (survivalwith freedom from death, mitral valve replacement, or redo-PMV) for both groups and were compared using the log-ranktest. Cox proportional hazards regression models were used totest the association between an elevated PVR and long-termoutcomes (including the covariates age, echocardiographicscore, mitral regurgitation after PMV of �3, mitral regurgita-tion before PMV of �2, and previous comissurotomy8). TRwas also tested as an independent predictor of adverse long-term outcomes using the same covariates.8 All analyses wereperformed using the Statistical Package for Social Sciences,version 17.0, for Windows (SPSS, Chicago, Illinois). p Values<0.05 were considered statistically significant for all tests.

Results

The study population consisted of 926 consecutivepatients who had undergone PMV at our institution. Of

Table 4Cox proportional hazards regression for long-term combined end point(death, mitral valve replacement, redo PMV)

Variable Hazard Ratio 95% ConfidenceInterval

p Value

Mitral regurgitation grade �3after PMV

3.54 2.66e4.77 <0.001

Mitral regurgitation grade �2before PMV

1.47 1.02e2.12 0.039

Age 1.013 1.005e1.021 <0.001Pulmonary vascular resistance

�4 WU1.05 0.84e1.32 0.61

Previous commissurotomy 1.53 1.19e1.96 0.01Echocardiographic score 1.162 1.099e1.230 <0.001

582 The American Journal of Cardiology (www.ajconline.org)

those, 663 (71.6%) had PVR <4 WU and 263 (28.4%) hadPVR �4 WU. The baseline characteristics of the studygroups are listed in Table 1. The hemodynamic findings inboth groups before and after PMV are listed in Table 2. Thehemodynamic parameters differed significantly between the2 groups. The procedural success rate in patients with PVR�4 WU was significantly lower than in those with PVR <4WU. However, on multivariate analysis, PVR �4 WU wasnot an independent predictor of PMV success (odds ratio1.018, 95% confidence interval 0.70 to 1.48, p ¼ 0.925).Also, a mean pulmonary artery pressure of �25 mm Hg wasnot an independent predictor of PMV success (data shownin Supplementary Materials).

The incidence of adverse events is listed in Table 3. Theincidence of in-hospital adverse events did not differ signifi-cantly between the 2 groups, with the exception of highernonprocedure-related deaths in patients with PVR �4 WU.Long-term clinical outcomes were available for 92% of thepatients at amedian follow-up of 3.2 years (interquartile range1.0 to 5.9). A lower mortality for patients with PVR <4 WUcompared with patients with PVR �4 during follow-up (log-rank test, p¼ 0.003) was recorded. No differences were foundin the need for mitral valve replacement or redo-PMVbetween patients with PVR �4 WU and PVR <4 WU (log-rank test, p ¼ 0.39 and p ¼ 0.89, respectively). Patients withPVR �4 WU experienced lower event-free survival (death,mitral valve replacement, redo PMV) than thosewith PVR<4WU (p ¼ 0.003). However, in the Cox regression analysis,PVR �4 WU was no longer an independent predictor ofevent-free survival (hazards ratio 1.05, 95% confidenceinterval 0.84 to 1.32, p ¼ 0.61; Table 4). Also, a meanpulmonary artery pressure of �25 mm Hg was not an inde-pendent predictor of event-free survival (data shown inSupplementary Materials).

Moderate and severe TR was observed in 23% and 6.4%of patients before PMV, respectively. Severe TR was anindependent predictor of event-free survival (death, mitralvalve replacement, redo PMV; hazard ratio 2.78, 95%confidence interval 1.87 to 4.13, p <0.001).

Discussion

Patients with mitral stenosis and severe PH have a poorprognosis.1 PH has long been considered a risk factor for pooroutcomes in patients undergoing mitral valve replacement,1,2

although this topic has remained controversial because some

conflicting data have been reported.3,4 The present report hasdemonstrated that an elevated PVR at PMV does not inde-pendently determine procedural success or long-term event-free survival and should not be regarded as a contraindicationfor PMV.Our results support the role of PMV in the treatmentof appropriately selected patients with mitral stenosisand PVR.

Chronic PH in patients with mitral stenosis has beenassociated with an elevated PVR, impedance, and high-amplitude arterial wave reflections.15 At least 3 mechanismscontribute to PH in mitral valve disease: passive transmissionof elevated left atrial pressure, reactive pulmonary arteriolarvasoconstriction, and morphologic changes in the pulmonaryvasculature. Because of the latter 2 mechanisms, the increasein pulmonary artery pressure is often disproportionate to theleft atrial hypertension, resulting in a significant increase inPVR.16,17 The reactive component is known to decreaseimmediately after mitral valve surgery; furthermore, it hasbeen shown that pulmonary vasoconstriction can be alleviatedin the short term using inhaled nitric oxide18 and might haveshort-term clinical benefits.18 However, medial hypertrophyor intimal fibrosis in the pulmonary arterioles might or mightnot regress after mitral valve replacement19; thus, PH canpersist or recur. It has been shown that the PVR can fall aftermitral valve replacement20; however, the data are limitedregarding PVR regression after PMV. The PVR can remainelevated despite the relief of mitral stenosis,21,22 but othershave shown a reduction in PVR either immediately afterPMV17,23 or a few months later.24 It might be that the passiveincrease in pulmonary pressure regresses immediately afterPMV but that regression of pulmonary pressure secondary toan increase in pulmonary artery resistance takes longer.

PMV has become the procedure of choice for manypatients with mitral stenosis.7 Follow-up studies have indi-cated that PMV is safe and well tolerated and associatedwith good short- and long-term outcomes.8,9 However, PMVsuccess and the subsequent outcomes depend on appropriatepatient selection. Despite the existence of several studies thatassessed the role of preprocedural variables in determining thePMV outcome,8 only a few studies17,21,23,25 have evaluatedthe effect of elevated PVR on procedural success and theshort- or long-term outcome. Large-scale studies of patientsundergoing PMV with elevated PVR with long-term follow-up data are lacking.

In the present study, patients with elevated PVR at PMVwere older, more symptomatic, and had less favorable valvemorphology. Accordingly, the rate of PMV success waslower. However, on multivariate analysis, PVR was not anindependent predictor of PMV success, supporting a role forPMV in patients with mitral stenosis and elevated PVR.Furthermore, elevated PVR did not determine the in-hospitalevent rate, except in the case of nonprocedure-related death.Finally, elevated PVR was associated with lower long-termevent-free survival but did not remain significant on multi-variate analysis. It is intuitive to assume that the presence ofsevere PH reflects more severe or long-standing mitralstenosis and will be associated with clinical and morpho-logic features that adversely affect the hemodynamicoutcome after PMV. However, the immediate and long-termoutcomes for this group of patients can be comparable tothose with lower PH. From our results, we suggest that

Valvular Heart Disease/Mitral Valvuloplasty and Pulmonary Hypertension 583

PMV remains a treatment option for appropriately selectedpatients with mitral stenosis, despite the presence ofelevated PVR. This strategy has been associated with lowermortality compared with previously reported surgical mitralvalve replacement data.5,6

TR is frequently present in patients with mitral valvedisease, and>1/3 of patients with mitral stenosis have at leastmoderate TR.26 The pathogenesis of TR in patients withmitral valve disease is complex and multifactorial. Long-standing PH can lead to right ventricular dysfunction andremodeling and thereby TR. PH can decrease after PMV ormitral valve surgery; however, our group has previously re-ported that in many patients, TR has not resolved afterPMV.27 Furthermore, we have previously reported that severeTR is an independent risk factor for adverse outcomes inpatients undergoing PMV.13 Therefore, it has been suggestedthat tricuspid valve repair combined with mitral valve surgeryshould be considered preferentially in patients with severemitral stenosis and severe TR, especially if atrial fibrillation oran enlarged right ventricle is present.28 We again identifiedTR as an independent predictor of adverse immediate andlong-term outcomes. Thus, patients with mitral stenosis andsevere TR should be considered high-risk patients for PMV,irrespective of the presence of PH.

The present study was a retrospective, single-center study.Thefindings of the present study, just aswith any observationalcohort, might not necessarily be generalizable to all patientswith mitral stenosis and elevated PVR who undergo PMV.Follow-up echocardiographic data could not be collected fora proportion of patients owing to the referral nature of ourclinical practice and therefore were not included. The vaso-reactivity of the PH and the postprocedural PVR data were notavailable.We also acknowledge that the lack of follow-up datafor pulmonary dynamics by catheterization after PMV wasa limitation. Nevertheless, our study has provided data froma real-world cohort of unselected patients and is the largeststudy to date of the effect of PVR on outcomes after PMV.

Acknowledgment: Dr. Cruz-Gonzalez acknowledges thesupport of the Spanish Society of Cardiology and MedtronicIberia S.A.

Disclosures

The authors have no conflicts of interest to disclose.

Supplementary Data

Supplementary data associated with this article can befound, in the online version, at http://dx.doi.org/10.1016/j.amjcard.2013.04.022.

1. Ward C, Hancock BW. Extreme pulmonary hypertension caused bymitral valve disease: natural history and results of surgery. Br Heart J1975;37:74e78.

2. Chaffin JS, Daggett WM. Mitral valve replacement: a nine-year follow-up of risks and survivals. Ann Thorac Surg 1979;27:312e319.

3. Scott WC, Miller DC, Haverich A, Mitchell RS, Oyer PE, Stinson EB,Jamieson SW, Baldwin JC, Shumway NE. Operative risk of mitralvalve replacement: discriminant analysis of 1329 procedures. Circu-lation 1985;72:II108eII119.

4. Christakis GT, Kormos RL, Weisel RD, Fremes SE, Tong CP, Herst JA,Schwartz L,Mickleborough LL, ScullyHE, GoldmanBS.Morbidity andmortality in mitral valve surgery. Circulation 1985;72:II120eII128.

5. Cesnjevar RA, Feyrer R, Walther F, Mahmoud FO, Lindemann Y, vonder Emde J. High-risk mitral valve replacement in severe pulmonaryhypertension—30 years experience. Eur J Cardiothorac Surg 1998;13:344e351 [discussion 351e352].

6. Jegaden O, Rossi R, Delahaye F, Montagna P, Delaye J, Delahaye JP,Mikaeloff P. Mitral valve replacement in severe pulmonary hyperten-sion. Long-term results. Arch Mal Coeur Vaiss 1991;84:1297e1301.

7. Bonow RO, Carabello BA, Kanu C, de Leon AC Jr, Faxon DP,Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O’Gara PT,O’Rourke RA, Otto CM, Shah PM, Shanewise JS, Smith SC Jr,Jacobs AK, Adams CD, Anderson JL, Antman EM, Faxon DP,Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R,Page RL, Riegel B. ACC/AHA 2006 guidelines for the management ofpatients with valvular heart disease: a report of the American College ofCardiology/American Heart Association Task Force on Practice Guide-lines (writing committee to revise the 1998Guidelines for theManagementof Patients With Valvular Heart Disease): developed in collaboration withthe Society of Cardiovascular Anesthesiologists: endorsed by the Societyfor Cardiovascular Angiography and Interventions and the Society ofThoracic Surgeons. Circulation 2006;114:e84ee231.

8. Palacios IF, Sanchez PL, Harrell LC, Weyman AE, Block PC. Whichpatients benefit from percutaneous mitral balloon valvuloplasty?Prevalvuloplasty and postvalvuloplasty variables that predict long-termoutcome. Circulation 2002;105:1465e1471.

9. Tuzcu EM, Block PC, Griffin BP, Newell JB, Palacios IF. Immediateand long-term outcome of percutaneous mitral valvotomy in patients 65years and older. Circulation 1992;85:963e971.

10. Palacios I, Block PC, Brandi S, Blanco P, Casal H, Pulido JI, Munoz S,D’Empaire G, Ortega MA, Jacobs M, Vlahakes G. Percutaneousballoon valvotomy for patients with severe mitral stenosis. Circulation1987;75:778e784.

11. Wilkins GT, Weyman AE, Abascal VM, Block PC, Palacios IF. Percu-taneous balloon dilatation of the mitral valve: an analysis of echocar-diographic variables related to outcome and the mechanism of dilatation.Br Heart J 1988;60:299e308.

12. Tuzcu EM, Block PC, Griffin B, Dinsmore R, Newell JB, Palacios IF.Percutaneous mitral balloon valvotomy in patients with calcific mitralstenosis: immediate and long-term outcome. J AmColl Cardiol 1994;23:1604e1609.

13. Sagie A, Schwammenthal E, Newell JB, Harrell L, Joziatis TB,Weyman AE, Levine RA, Palacios IF. Significant tricuspid regurgita-tion is a marker for adverse outcome in patients undergoing percuta-neous balloon mitral valvuloplasty. J Am Coll Cardiol 1994;24:696e702.

14. Block PC, Tuzcu EM, Palacios IF. Percutaneous mitral balloon val-votomy. Cardiol Clin 1991;9:271e287.

15. Kussmaul WG III, Altschuler JA, Herrmann HC, Laskey WK. Effectsof pacing tachycardia and balloon valvuloplasty on pulmonary arteryimpedance and hydraulic power in mitral stenosis. Circulation1992;86:1770e1779.

16. Levine MJ, Weinstein JS, Diver DJ, Berman AD, Wyman RM,Cunningham MJ, Safian RD, Grossman W, McKay RG. Progressiveimprovement in pulmonary vascular resistance after percutaneous mitralvalvuloplasty. Circulation 1989;79:1061e1067.

17. Fawzy ME, Osman A, Nambiar V, Nowayhed O, El DA, Badr A,Canver CC. Immediate and long-term results of mitral balloon valvu-loplasty in patients with severe pulmonary hypertension. J Heart ValveDis 2008;17:485e491.

18. Fernandes JL, Sampaio RO, Brandao CM, Accorsi TA, Cardoso LF,Spina GS, Tarasoutchi F, Pomerantzeff P, Auler JO Jr, Grinberg M.Comparison of inhaled nitric oxide versus oxygen on hemodynamics inpatients with mitral stenosis and severe pulmonary hypertension aftermitral valve surgery. Am J Cardiol 2011;107:1040e1045.

19. Foltz BD, Hessel EA II, Ivey TD. The early course of pulmonary arteryhypertension in patients undergoing mitral valve replacement withcardioplegic arrest. J Thorac Cardiovasc Surg 1984;88:238e247.

20. Zener JC, Hancock EW, Shumway NE, Harrison DC. Regression ofextremepulmonary hypertension aftermitral valve surgery.AmJCardiol1972;30:820e826.

21. Maoqin S, Guoxiang H, Zhiyuan S, Luxiang C, Houyuan H, Liangyi S,Ling Z, Guoqiang Z. The clinical and hemodynamic results of mitral

584 The American Journal of Cardiology (www.ajconline.org)

balloon valvuloplasty for patients with mitral stenosis complicated bysevere pulmonary hypertension. Eur J Intern Med 2005;16:413e418.

22. Block PC, Palacios IF. Pulmonary vascular dynamics after percuta-neous mitral valvotomy. J Thorac Cardiovasc Surg 1988;96:39e43.

23. Alfonso F, Macaya C, Hernandez R, Banuelos C, Iniguez A, Goicolea J,Fernandez-Ortiz A, Zamorano J, Zarco P. Percutaneous mitral valvulo-plasty with severe pulmonary artery hypertension. Am J Cardiol1993;72:325e330.

24. Dev V, Shrivastava S. Time course of changes in pulmonary vascularresistance and the mechanism of regression of pulmonary arterialhypertension after balloon mitral valvuloplasty. Am J Cardiol 1991;67:439e442.

25. Fawzy ME, Mimish L, Sivanandam V, Lingamanaicker J, Patel A,Khan B, Duran CM. Immediate and long-term effect of mitral balloon

valvotomy on severe pulmonary hypertension in patients with mitralstenosis. Am Heart J 1996;131:89e93.

26. Sagie A, Freitas N, Chen MH, Marshall JE, Weyman AE, Levine RA.Echocardiographic assessment of mitral stenosis and its associatedvalvular lesions in 205 patients and lack of association with mitralvalve prolapse. J Am Soc Echocardiogr 1997;10:141e148.

27. Sagie A, Schwammenthal E, Palacios IF, King ME, Leavitt M,Freitas N, Weyman AE, Levine RA. Significant tricuspid regurgita-tion does not resolve after percutaneous balloon mitral valvotomy.J Thorac Cardiovasc Surg 1994;108:727e735.

28. Song H, Kang DH, Kim JH, Park KM, Song JM, Choi KJ, Hong MK,Chung CH, Song JK, Lee JW, Park SW, Park SJ. Percutaneous mitralvalvuloplasty versus surgical treatment in mitral stenosis with severetricuspid regurgitation. Circulation 2007;116:I246eI250.