Persistent Tricuspid Regurgitation and Its Predictor in AdultsAfter Percutaneous and Isolated Surgical Closure of Secundum
Atrial Septal Defect
Manatomo Toyono, MD, PhDa, Richard A. Krasuski, MDa, Gosta B. Pettersson, MD, PhDb,Yoshiki Matsumura, MD, PhDa, Tetsuhiro Yamano, MD, PhDa, and Takahiro Shiota, MD, PhDa,c,*
The fate of functional tricuspid regurgitation (TR) after closure of a secundum atrial septaldefect (ASD) without any corrective tricuspid valve (TV) surgery remains unclear. Weinvestigated this and the predictors of persistent TR after ASD closure. Thirty-two con-secutive patients with moderate or severe TR before ASD closure were examined. Of these,23 underwent percutaneous ASD closure, and 9 underwent isolated surgical ASD closure.The left ventricular end-diastolic volume, left ventricular ejection fraction, right ventricularend-diastolic area, right ventricular fractional area change, right ventricular sphericalindex, right atrial area, TV annular diameter, TV tethering height, pulmonary arterysystolic pressure, and pulmonary/systemic blood flow ratio were determined by echocardi-ography before and early after ASD closure. The color Doppler maximal jet area was usedto assess the severity of TR. After ASD closure, the jet area decreased for all patients (p �0.009); however, 16 patients (50%) had persistent TR. Multivariate analysis revealed thatonly pulmonary artery systolic pressure before ASD closure was related to the TR jet areaafter ASD closure (p � 0.003). A pulmonary artery systolic pressure of >60 mm Hgpredicted persistent TR with 100% sensitivity and 63% specificity. In conclusion, functionalTR was ameliorated after percutaneous and isolated surgical ASD closure, althoughpersistent TR was common. The presence of pulmonary hypertension before ASD closurepredicted persistent TR; therefore, corrective TV surgery should be considered at ASDclosure in adult patients with moderate or severe TR and concomitant pulmonary
Percutaneous closure is now offered as an alternative tourgery for selected patients with secundum atrial septalefect (ASD).1 Currently, approximately 75% of patientsith secundum ASD are treated using the percutaneous
echnique, with the remaining patients undergoing surgery.2
ew studies have addressed the effects of percutaneous andsolated surgical ASD closure on patients with substantialricuspid regurgitation (TR). Furthermore, the predictors ofersistent TR after ASD closure remain unknown. The aimf the present study was to investigate the outcome ofubstantial TR after percutaneous and isolated surgical clo-ure of the secundum ASD. Moreover, to establish whetherorrective tricuspid valve (TV) surgery is essential at ASDlosure, we also attempted to identify the predictors ofersistent TR after ASD closure.
ethods
In the present study, we reviewed the records of 119onsecutive adult patients (�17 years old) who had under-
Departments of aCardiovascular Medicine, and bThoracic and Cardio-ascular Surgery, Cleveland Clinic, Cleveland, Ohio; and cCardiac Non-nvasive Laboratory, Cedars-Sinai Medical Center, and David Geffenchool of Medicine at UCLA, Los Angeles, California. Manuscript re-eived February 25, 2009; revised manuscript received and accepted May, 2009.
one percutaneous closure of secundum ASDs and 61 con-ecutive adult patients who had undergone isolated surgicallosure of secundum ASDs at the Cleveland Clinic fromebruary 2002 to February 2007. The exclusion criteria for
he study were as follows: (1) ASDs �10 mm in diameter,2) less than moderate TR before ASD closure, (3) co-orbid cardiac disease, (4) organic lesions of the TV oritral valve, and (5) the absence of sufficient echocardio-
raphic images. A total of 32 patients who had moderate orevere TR before ASD closure were selected for additionaltudy. Of these patients, 23 (72%) underwent percutaneousSD closure and 9 (28%) isolated surgical ASD closure.he Institutional Review Board for Clinical Research ap-roved the interventional cardiology, surgery, and echocar-iography databases used in the present study.
All the patients were examined using 2-dimensional andoppler transthoracic echocardiography 21 � 20 days be-
ore and 4 � 3 days after ASD closure. The echocardio-raphic examination was performed in a standard mannersing 1 of the 4 commercially available systems: Sonos500 or iE33 (both from Philips Medical Systems, Bothell,ashington), Vivid 7 (General Electric Medical Systems,ilwaukee, Wisconsin), or Acuson Sequoia C512 (Sie-ens, Mountain View, California). Data analysis was per-
ormed using an off-line measurement system (ProSolvardioVascular, version 3.5, ProSolv, Indianapolis, Indiana).
The left ventricular (LV) volume and ejection fraction
ere determined using the modified Simpson algorithm.3
857Congenital Heart Disease/Persistent TR After ASD Closure
he right ventricular (RV) area and RV fractional areahange were quantified according to the guidelines providedy the American Society of Echocardiography.4 To evaluatehe changes in RV geometry, the RV spherical index wasalculated as the ratio of the RV end-systolic area to theaximal RV long-axis dimension in the apical 4-chamber
iew.5 The right atrial area was measured in the same viewt end-systole. The minimal diameter of the TV annulus andhe TV tethering height were also measured in the sameiew during mid-systole using a frame-by-frame technique.6
he severity of TR was assessed on the basis of the spatialistribution of the central regurgitant jet within the righttrium by color Doppler flow mapping. TR was graded asild if the jet area was �5 cm2, moderate if it was 5 to 10
m2, and severe if it was �10 cm2.7 Persistent TR wasefined as moderate or severe TR after ASD closure. Usinghe TV flow velocity determined by continuous-wave Dopp-er echocardiography, the pulmonary artery systolic pres-ure was calculated using the simplified Bernoulli equation,y adding the right atrial pressure estimated from the respi-atory index of the inferior vena cava and subtracting theressure gradient across the RV outflow tract.8,9 The ratio ofulmonary blood flow to systemic blood flow was computedsing previously established methods.10 An average of �5eterminations of each echocardiographic variable was an-lyzed. In addition, 12-lead electrocardiograms obtained forll the participants were reviewed to determine whethertrial fibrillation was present.
The quantitative and categorical data are presented as theean � standard deviation and as percentages, respectively.he variables of these 2 groups were compared using thetudent paired or unpaired t test for quantitative data and theilcoxon signed rank test or the Mann-Whitney U test for
ategorical data, as appropriate. To analyze the relationetween the variables measured before ASD closure and theR jet area recorded after the closure, univariate linear
egression analysis was performed using either the Pearsonorrelation coefficient or the Spearman rank correlationoefficient, as appropriate. The variables selected for uni-ariate analysis were as follows: age at surgery, male gen-er, presence of atrial fibrillation, LV end-diastolic volume,V ejection fraction, RV end-diastolic area, RV fractionalrea change, RV spherical index, right atrial area, minimalV annular diameter, TV tethering height, TR jet area,ulmonary artery systolic pressure, and the ratio of pulmo-ary blood flow to systemic blood flow. Subsequently, theignificant data obtained from the univariate analysis werepplied to multivariate linear regression analysis to deter-ine the independent factors associated with the TR jet area
fter ASD closure. p Value �0.05 was considered statisti-ally significant. Statistical analysis was performed usingommercially available software (Statistical Package forocial Sciences, version 13.0, for Windows, SPSS, Chi-ago, Illinois).
From the echocardiographic data, 10 random imagesere analyzed by 2 blinded observers and by a singlebserver at 2 different times to assess the interobserver andntraobserver differences with regard to measurements ofhe TR jet area and the pulmonary artery systolic pressure.hese differences were analyzed by determining the Pear-
on correlation coefficient and using the Bland-Altman c
echnique.11 These methods were also used to compare theliasing velocities used in measurements of the TR jet areaefore and after ASD closure.
losure, 9 (39%), 13 (57%), and 1 (4%) were considered to
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858 The American Journal of Cardiology (www.AJConline.org)
ave New York Heart Association class I, II and III, re-pectively. Of the 9 patients who underwent isolated surgi-al ASD closure, 4 (45%), 3 (33%), and 2 (22%) wereraded as having New York Heart Association class I, II,nd III, respectively. The characteristics of the patients whonderwent percutaneous and isolated surgical ASD closurere listed in Table 1. The former group was significantlylder than the latter. Before closure, the patients who un-erwent isolated surgical ASD closure exhibited a signifi-antly greater RV spherical index than those in the otherroup. Furthermore, the patients who underwent isolatedurgical ASD closure exhibited greater RV end-diastolicrea values and pulmonary blood flow to systemic bloodow ratios and, in contrast, lower RV fractional area change
igure 1. Examples of improvement in the severity of TR after ASD closurertery systolic pressure of this patient (71-year-old man) was 44 mm Hg.
igure 2. Changes in the TR jet area from before to after percutaneous and ifter percutaneous and isolated surgical ASD closure. The patients with df 77 mm Hg before ASD closure (right arrow). In contrast, the patient wressure of 44 mm Hg before ASD closure (left arrow).
alues than those who underwent percutaneous ASD clo- p
ure. However, none of these differences were statisticallyignificant. The minimal TV annular diameter, TV tetheringeight, and pulmonary artery systolic pressure were similarn both groups. In the patients who underwent percutaneousSD closure, the ratio of pulmonary blood flow to systemiclood flow using the Fick principle was 2.1 � 0.8; thisverage value was almost equivalent to that derived fromoninvasive echocardiographic methods. The average size ofhe ASD determined by transesophageal echocardiographyas 2.0 � 0.6 and 2.3 � 1.6 cm in those who underwentercutaneous ASD closure and those who underwent isolatedurgical ASD closure, respectively. The pressure gradientcross the RV outflow tract was �10 mm Hg in all patients.
The variables that were determined before and after
t corrective TV surgery. Before percutaneous ASD closure, the pulmonaryverity of TR improved markedly after ASD closure.
surgical ASD closure. The average TR jet area was significantly decreasedincrease in the TR jet area had had a pulmonary artery systolic pressureramatic decrease in the TR jet area had had a pulmonary artery systolic
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ercutaneous and isolated surgical ASD closure are listed in
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859Congenital Heart Disease/Persistent TR After ASD Closure
able 2. The presence of atrial fibrillation, RV end-diastolicrea, RV spherical index, right atrial area, and TV tetheringeight were significantly decreased, and the LV end-dia-tolic volume was significantly increased, after ASD clo-ure. No appreciable change was noted in the pulmonaryrtery systolic pressure after ASD closure.
No significant difference in the TR jet area was recordedor the patients of either group before ASD closure (Table). Of the patients who underwent percutaneous ASD clo-ure, 16 (70%) had moderate TR and 7 (30%) severe TR. Ofhose who underwent isolated surgical ASD closure, 667%) had moderate TR and 3 (33%) had severe TR. AfterSD closure, none of the patients exhibited a residual left-
o-right shunt, as determined by a combination of coloroppler flow mapping and intravenous saline injection with
he Valsalva maneuver. Furthermore, no significant differ-nce was found between the patient groups with regard tohe TR jet area measured after ASD closure. The aliasingelocity used for measurement of the TR jet area was 59 �
igure 3. Changes in the severity of TR from before to after percutaneous annd severe TR after ASD closure.
able 3elationships between variables before atrial septal defect (ASD) closurend tricuspid regurgitation (TR) jet area after ASD closure (n � 32)
ight ventricular spherical index 0.08ight atrial area 0.64 �0.001 0.5V annular diameter 0.59 0.001 0.4V tethering height 0.4ulmonary artery systolic pressure 0.76 �0.001 0.003p/Qs 0.2R jet area 0.1
Qp/Qs � ratio of pulmonary blood flow to systemic blood flow.
and 58 � 7 cm/s before and after ASD closure, respec- c
ively. These variables were fairly consistent in all theatients before and after ASD closure (r � 0.88, p �0.001),nd the mean difference in the aliasing velocities between 2oints was 1 � 2 cm/s.
Before percutaneous and isolated surgical ASD closure,he TR jet area showed a significant correlation with theight atrial area and TV tethering height (r � 0.62 and r �.49, respectively; p �0.01). After ASD closure, the TR jetrea significantly decreased from 10 � 5 to 6 � 5 cm2
Figures 1 and 2 and Table 2). However, of the 32 patients,ersistent TR was found in 16 (50%); it was moderate in 7nd severe in 9 (Figure 3). Univariate analysis indicated aignificant correlation between the right atrial area, minimalV annular diameter, and pulmonary artery systolic pres-ure before ASD closure and the TR jet area after ASDlosure (Table 3). When multivariate analysis was per-ormed using these significant variables, the pulmonaryrtery systolic pressure before ASD closure was identifieds the sole factor associated with the TR jet area after ASD
ed surgical ASD closure. Of 32 patients, 16 (50%) had persistent moderate
igure 4. Regression plots showing correlation between pulmonary arteryPA) systolic pressure before ASD closure and TR jet area after ASDlosure. The PA systolic pressure before ASD closure correlated signifi-antly with the TR jet area after ASD closure. Of the 6 patients with a PAystolic pressure of �60 mm Hg before ASD closure, 1 patient had a mildecrease in the TR jet area from 7 to 5 cm2 after percutaneous ASD closurearrow). This patient showed a decrease in the PA systolic pressure from9 to 45 mm Hg after ASD closure.
d isolat
losure (Figure 4 and Table 3). When the pulmonary artery
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860 The American Journal of Cardiology (www.AJConline.org)
ystolic pressure was �60 mm Hg, it predicted persistentR with 100% sensitivity and 63% specificity. When theulmonary artery systolic pressure was �50 mm Hg, itredicted less-than-severe TR after ASD closure with 85%ensitivity and 83% specificity. The pulmonary artery sys-olic pressure after ASD closure also showed a significantorrelation with the TR jet area after ASD closure (r � 0.75,�0.001).The TR jet area and pulmonary artery systolic pressure
easured by the 2 blinded observers were fairly consistentr � 0.90 and r � 0.99, respectively; p �0.001). The meanifference in the TR jet area and pulmonary artery systolicressure was 0.4 � 1.2 cm2 and 2 � 1 mm Hg, respectively.urthermore, a correlation was noted in the intraobservereasurements for the TR jet area and pulmonary artery
ystolic pressure (r � 0.91 and r � 0.995, respectively;�0.001). The mean difference in the TR jet area and
ulmonary artery systolic pressure were 0.2 � 0.9 cm2 and� 1 mm Hg, respectively.
iscussion
In the present study, persistent TR was observed in 50%f the patients, although functional TR was reduced afterercutaneous and isolated surgical ASD. This limited ame-ioration of functional TR might be reflective of the incom-lete improvement in right atrial and RV dilation after ASDlosure in the case of older patients, as has been demon-trated by previous investigators.12 Substantial TR has beenemonstrated to be associated with poor short-term andong-term survival in patients with various cardiac disea-es13–15; therefore, to decide whether corrective TV surgeryhould be performed at ASD closure, it is important todentify patients who are likely to have persistent TR. In theresent study, we found that the pulmonary artery systolicressure before ASD closure was a key predictive parameteror persistent TR.
The patients who underwent isolated surgical ASD clo-ure had a significantly greater RV geometric abnormalityefore ASD closure than those with percutaneous ASDlosure, although the former patients were significantlyounger than the latter. Furthermore, the patients who un-erwent isolated surgical ASD closure were more markedlyffected by left-to-right shunts, even though the duration ofhe disease had been short. These findings could be ex-lained by patient selection, namely, percutaneous closureight not be suitable for patients with a large ASD.It has been reported that the pulmonary artery pressure is
levated in 5% to 10% of adult patients with ASD who haveot been treated for the defect, in relation to advanced age,16
emale gender,17 decompensated RV failure,18 and pulmo-ary artery thromboembolism.19 These factors eventuallyead to an increase in cardiovascular mortality.20 In theresent study, a pulmonary artery systolic pressure of �60m Hg before ASD closure was identified as a predictor of
ersistent TR. To the best of our knowledge, this is the firsttudy to identify the predictor of persistent TR after ASDlosure. On the basis of our results, corrective TV surgeryan be recommended at ASD closure in adult patients withoderate or severe TR and a pulmonary artery systolic
ressure of �60 mm Hg. In addition, the present study has
hown that patients with a pulmonary artery systolic pres-ure of �50 mm Hg are unlikely to develop severe TR afterSD closure and can be safely treated with percutaneousSD closure instead of surgery.In the present study, the pulmonary artery systolic pres-
ure did not show a significant decrease, even after ASDlosure. This finding is consistent with that of a previoustudy demonstrating that pulmonary hypertension is not aare condition among adult patients who have undergoneSD closure.21 In patients with ASD, it has been shown that
he hemodynamic mechanisms leading to pulmonary hyper-ension include prolonged volume overload in the pulmo-ary circulation.22 Therefore, early interventions could playn important role in ameliorating pulmonary hypertensionnd, ultimately, preventing the development of persistentR after ASD closure.
One patient in the present study exhibited nearly mild TRfter ASD closure, despite having evident pulmonary hy-ertension before ASD closure (Figure 2). This patient had35% decrease in the pulmonary artery systolic pressure
fter ASD closure. Thus, a decrease in the pulmonary arteryystolic pressure might reduce the severity of TR after ASDlosure. A previous case report revealed that the reductionn pulmonary artery pressure by oral sildenafil was associ-ted with a reduced TR in severe pulmonary hypertension.23
The present study had several limitations. First, the RVystolic function was largely preserved in the patients, asndicated by the RV fractional area change. It is not clearow the results of the present study could be applied toatients with RV systolic dysfunction. Second, because ofhe retrospective nature of our study, the echocardiogramsere not obtained specifically to evaluate the anatomy and
unction of the TV annulus. This can be overcome by arospective analysis to obtain constant examinations us-ng identical echocardiographic machines and techniques.hird, the sample size was relatively small. Although mostf the results fulfilled the criteria for statistical significance,dditional studies are needed to validate our results in aarger population. Finally, the timing of the evaluation afterSD closure was quite short, and we could not provide
ong-term follow-up results. Therefore, it is unclear howersistent TR might change over a long period and whethert might produce reverse remodeling of the RV and theulmonary vasculature. A prospective long-term follow-uptudy is clearly indicated to further assess persistent TRfter ASD closure.
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