Detection of pulmonary vein stenosis by transesophageal echocardiography: Comparison with multidetector computed tomography

Imaging and Diagnostic Testing

Detection of pulmonary vein stenosis by transesophageal echocardiography: Comparison with multidetector computed tomography Gardar Sigurdsson, MD,a Richard W. Troughton, MB, ChB, PhD,a Xiao-Fang Xu, MD,a Holger P. Salazar, MD, FACC,a Oussama M. Wazni, MD,a Richard A. Grimm, DO, FACC,a Richard D. White, MD, FACC,a,b Andrea Natale, MD, FACC,a and Allan L. Klein, MD, FACCa Cleveland, OH

Objective

The objective of this study is to compare the use of transesophageal echocardiography (TEE) vs multidetector computed tomography (MDCT) for detecting pulmonary vein stenosis.

Background Pulmonary vein isolation is increasingly used to treat atrial fibrillation. Pulmonary vein stenosis remains a potential complication of pulmonary vein isolation and ideal methods for detection of stenosis are still to be determined. Methods Thirty-six subjects who underwent pulmonary vein isolation returned for follow-up MDCT and TEE. Percent diameter loss was reported for each pulmonary vein stenosis by MDCT. A 50% narrowing was considered as an indication of a stenosis. Pulsed-wave Doppler using TEE was used to measure peak velocities of all pulmonary veins. Results Multidetector computed tomography and TEE were performed in all subjects (58 F 10 years) at 4 F 2 months after pulmonary vein isolation. Atrial fibrillation was present in 14% at time of follow-up. Multidetector computed tomography was able to evaluate all 4 (100%) pulmonary veins in 36 subjects, whereas full interrogation by TEE was possible in 138 (96%) of 144 veins. Pulmonary vein stenosis N50% by MDCT was present in 7 pulmonary veins. Analysis of the receiver operating curve for TEE showed that it had optimum detection of pulmonary vein stenosis at peak velocities ~100 cm/s with 86% sensitivity and 95% specificity. Area under the curve for TEE was 0.93. Clinically significant stenosis was observed in 2 subjects and was detected by both TEE and MDCT. Conclusions Transesophageal echocardiography was able to detect most pulmonary veins with good sensitivity and specificity in comparison to MDCT. Pulmonary veins may be visualized more frequently by MDCT; however, TEE provides additional data about the functional significance of a pulmonary vein stenosis. (Am Heart J 2007;153:80026.) Atrial fibrillation is the most common sustained arrhythmia seen in clinical practice.1 It is associated with a 2-fold increase in cardiovascular mortality and morbidity.2,3 Pharmacologic therapy is the first line of treatment when pursuing rhythm control in symptomatic patients,4 but dissatisfaction by both physicians and subjects has resulted in a growing interest in the nonpharmacologic treatment of atrial fibrillation.5 Pulmonary vein isolation with transcatheter radiofrequency ablation is gaining popularity with a success rate ranging from 62% to 90%.6,7 The main complication of pulmo-

From the aDepartment of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, and bRadiology Division, Cleveland Clinic, Cleveland, OH. Submitted August 4, 2006; accepted January 30, 2007. Reprint requests: Allan L. Klein, MD, FACC, Cleveland Clinic, Cardiovascular Medicine Division, 9500 Euclid Ave, Desk F15, Cleveland, OH 44195. E-mail: [email protected] 0002-8703/$ - see front matter n 2007, Published by Mosby, Inc. doi:10.1016/j.ahj.2007.01.039

nary vein isolation is pulmonary vein stenosis8 with incidence ranging from 0% to 42% depending on several factors including definition of stenosis, method of ablation, and imaging modality.9-14 Initial methods of radiofrequency ablation involved ablating in the orifice of the pulmonary veins, which lead to high numbers of pulmonary vein stenosis. More current methods of radiofrequency ablation require working primarily in the antrum of the pulmonary veins and this has led to a substantial decrease in frequency of pulmonary vein stenosis. Methods for detecting pulmonary vein stenosis include fluoroscopic angiography,9 computed tomography (CT),14 magnetic resonance imaging (MRI),10-13 transesophageal echocardiography (TEE),10,11,15 and intracardiac echocardiography.7 Computed tomography and MRI have been considered the gold standards for pulmonary vein stenosis detection, although both, because of their dependency on electrocardiographic (ECG) gating and need for slow and regular rhythm for good imaging quality, may be limited in the setting of atrial fibrillation. Furthermore, these

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Table I. Demographics of subjects within the study Demographics of subjects Age (y) Women, n (%) Atrial fibrillation during follow-up, n (%) Days after ablation (range) History of subjects Coronary disease, n (%) Hypertension, n (%) Cerebrovascular event, n (%) Diabetes, n (%) Lone atrial fibrillation, n (%) Heart rate (beat/min) Left ventricular ejection fraction (%) Left atrial area (cm2) Right atrial area (cm2)

Table III. Transesophageal echocardiography results for peak velocity, both systolic and diastolic

58 F 10 5 (14) 5 (14) 117 F 63 (63-337) 4 (11) 6 (17) 4 (11) 2 (6) 26 (72) 74 F 19 53 F 9 21 F 6 22 F 5

Mean ± SD

Visualized, n (%)

LUPV LLPV RUPV RLPV

(100%) (89%) (100%) (94%)

Peak velocity diastolic (cm/s)

66 F 43 56 F 40 62 F 33 51 F 224

61 51 67 56

F F F F

34 304 27 264

4P b .05 between upper and lower pulmonary vein.

Table IV. Sensitivity and specificity of TEE with variable peak velocities in detecting z50% diameter loss stenosis by MDCT Peak velocity (cm/s)

Table II. Number of stenosis (% diameter loss) detected by MDCT in 36 subjects Visualized, n (%)

36 32 36 34

Peak velocity systolic (cm/s)

<29%

30%-49%

50%-69%

> – 70%

29 28 31 33

3 6 4 3

3 2 1 0

1 0 0 0

N80 N100 N120

Sensitivity (%)

Specificity (%)

PPV (%)

NPV (%)

86 86 71

87 95 96

26 46 56

99 99 98

PPV, Positive predictive value; NPV, negative predictive value.

LUPV LLPV RUPV RLPV

36 36 36 36

(100%) (100%) (100%) (100%)

LUPV, Left upper pulmonary vein; LLPV, left lower pulmonary vein; RUPV, right upper pulmonary vein; RLPV, right lower upper pulmonary vein.

methods provide limited physiologic assessment of the pulmonary veins.16 Finally, the degree of radiation used in serial CT studies is not inconsequential where current methods result in radiation equivalent to nuclear stress studies and lifetime accumulation of medical radiation is of concern.17 On the other hand, TEE is well suited for imaging the pulmonary veins and pulsed-wave Doppler is used daily to assess flow in the pulmonary veins in patients with mitral regurgitation.18 Preliminary studies using TEE have demonstrated greater sensitivity in detecting pulmonary vein stenosis than studies using CT or MRI.10,11,15 However, there are no current guidelines that address the role of imaging modalities for detection of pulmonary vein stenosis.4,19 Therefore, we sought to compare TEE to MDCT in detecting pulmonary vein stenosis in subjects after pulmonary vein isolation.

Methods Study population Thirty-six consecutive subjects (31 men) with a history of paroxysmal or persistent atrial fibrillation were studied during follow-up after pulmonary vein isolation for atrial fibrillation. The study received approval from the institutional review board of the Cleveland Clinic Foundation. Subjects gave informed consent before the pulmonary vein isolation procedure. The approach for pulmonary vein isolation has been previously described.7,20 Intracardiac echocardiography-guided

mapping and ablation of all pulmonary vein ostia was performed with the use of a 10F, 64-element, phased-array ultrasound imaging catheter (AcuNave, Acuson, Mountainview, CA) introduced through an 11F sheath through the left femoral vein. A decapolar Lasso catheter (Biosense Webster Inc, Baldwin Park, CA) was used for circular mapping and isolation of all pulmonary veins. Ablation was extended to the pulmonary vein antrum in front of the tubelike portion of the pulmonary veins. Radiofrequency energy was delivered with the use of a cool-tipped ablation catheter (EP Technologies, San Jose, CA). Energy delivery was titrated with the operator watching for microbubble formation. Contrast-enhanced MDCT was performed with a 16-slice scanner (Sensation-16, Siemens Medical Systems, Forchheim, Germany) with retrospective ECG gating and temporal resolution of 185 to 210 ms. Volumetric retrospective ECG-guided reconstructions were done of the diastolic phases (50%-65% of the cardiac cycle) to minimize cardiac motion artifact with slice thickness of 1.0 mm and 50% overlap. Contrast injection (Ultravist 350, Schering, Germany) was done at a rate of 3.0 to 3.5 mL/s, for a total of 100 to 120 mL. Multidetector computed tomography was reviewed by a cardiac radiologist blinded to the TEE results. The percent diameter loss in pulmonary vein lumen by MDCT [(narrowest diameter / adjacent normal lumen diameter)  100] was reported for all veins based on oblique, multiplanar, and thin maximum-intensity-projection reconstruction (Leonardo Workstation, Siemens Medical Solutions, Erlangen, Germany). Transesophageal echocardiography was performed under conscious sedation using a commercially available 5- to 7-MHz transducer attached to an echo machine (ATL 5000, Philips, Andover, MA). During the TEE, most patients were on their left side or on their back in a semireclined position. Visualization of all 4 pulmonary veins was attempted in all cases. Transesophageal echocardiography imaging included color flow map imaging and pulsed-wave

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Table V. Discrepancy between MDCT findings and TEE findings

Case Case Case Case Case Case Case Case Case Case Case

2 2 2 11 16 16 16 17 28 30 36

Vein location

MDCT (%)

TEE (cm/s)

LLPV RUPV RLPV LUPV LUPV LLPV RUPV RUPV RUPV RLPV LUPV

45 0 40 50 45 45 40 42 20 0 15

Not evaluated 117 106 60 197 185 189 125 101 122 132

Figure 1

Figure 2

Receiver operating curve analysis for detection of pulmonary vein stenosis by TEE showed 86% sensitivity and 95% specificity with area under the curve of 0.93. (Pulmonary vein stenosis is defined as z50% diameter loss by MDCT.)

Figure 3

Scatterplot with results from all pulmonary veins comparing percent stenosis by MDCT to peak velocity measured by TEE. The data points for 2 symptomatic patients are identified within the plot. Patient A had 1 pulmonary vein that was not detected by echocardiography.

Doppler imaging for each vein. The sample volume for pulsedwave Doppler was 4 to 5 mm, and it was placed 1 cm into the pulmonary vein. Color flow was often used to guide the placement of the sample volume. The TEE studies were digital archived, and off-line analysis (Prosolv, Indianapolis, IN) was performed by observers who were blinded to the results of the MDCT. Transesophageal echocardiography measurements included peak velocity and velocity time integrals for each pulmonary vein.

Statistical analysis Continuous variables are summarized as mean F SD. Paired Student t test was used to compare peak velocities between pulmonary veins. For receiver operating curve (ROC) analysis of MDCT, the highest measured peak velocity was used by TEE during systole, diastole, or the maximum peak velocity for (either systolic or diastolic) each pulmonary vein. We arrived at the optimum cutoff point of 100 cm/s for peak velocities by TEE, by selecting the point on the ROC curve that maximized both sensitivity and 1-specificity when using 50% stenosis by MDCT as reference. Results of ROC

Receiver operating curve analysis for detection of pulmonary vein stenosis by MDCT showed 73% sensitivity and 97% specificity with area under the curve of 0.90. (Pulmonary vein stenosis is defined as peak velocity N100 cm/s by TEE.)

analysis for peak velocities within diastolic phase are expressed in results, tables, and figures. Statistical analysis was performed with MedCalc for Windows, version 7.4.1.0 (MedCalc Software, Mariakerke, Belgium). A P value b.05 was considered significant.

Results Study characteristics The clinical characteristics of subjects are listed in Table I. Five (14%) subjects were in atrial fibrillation

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Figure 4

(A) Diameter loss of 50% to LUPV by contrast-enhanced CT. (B) Color Doppler TEE with aliasing at the ostium of LUPV. (C) Pulsed-wave Doppler by TEE showing a peak velocity of 184 cm/s.

at the time of follow-up. All subjects underwent MDCT and TEE on the same day at a mean of 4 F 2 months after pulmonary vein isolation. These studies were conducted during the period between January 2002 and February 2003.

MDCT evaluation All 4 pulmonary veins were detected by MDCT in all subjects (100%). Multidetector computed tomography detected stenosis N30% in 23 (16%) of 144 visualized pulmonary veins, and stenosis z50% was found in 7 (5%) of 144 visualized pulmonary veins (Table II). TEE evaluation Transesophageal echocardiography detected adequate flow in the LUPV in 36 (100%) of 36, LLPV in 32 (89%) of 36, RUPV in 36 (100%) of 36, and right lower pulmonary vein in 34 (94%) of 36 subjects. Transesophageal echocardiography detected stenosis in 15 (11%) of 138 veins when using a peak velocity of z100 cm/s as cutoff, 31 (22%) of 138 veins when using a peak velocity of z 80 cm/s as cutoff, and 11 (8%) of 138 veins when using peak velocity of z120 cm/s as cutoff. There was a significantly higher average peak velocity for upper pulmonary veins compared to lower pulmonary veins on both sides (Table III). No significant difference was found in the average peak velocities of pulmonary veins when comparing the left- vs right-sided pulmonary veins.

MDCT and TEE comparison Sensitivity and specificity of TEE in detecting z50% diameter loss stenosis by MDCT is shown in Table IV. Discrepancy between stenosis detected by MDCT and findings by TEE is shown in Table V. Scatterplot with results from all pulmonary veins comparing percent stenosis by MDCT to peak velocity measured by TEE is shown in Figure 1. The data points for 2 symptomatic patients are identified within the plot. Receiver operating curve analysis of TEE measurement showed 86% sensitivity and 95% specificity with area under the curve of 0.93 if pulmonary vein stenosis was defined as diameter loss z50% by MDCT (Figure 2). There was no statistical significance between ROC curves while using systolic or diastolic measures of peak velocities. Clinically significant stenosis occurred in 2 subjects (with peak velocities of 150 and 200 cm/s) and was accurately detected by both TEE and MDCT.

Discussion Pulmonary vein stenosis is a well-known complication of pulmonary vein isolation, and detection of stenosis often requires noninvasive imaging during follow-up because of frequent lack of symptoms despite the presence of hemodynamically significant stenosis.16 The results of our study show that TEE was able to detect adequate flow in most pulmonary veins (96%), and with

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good sensitivity (86%) and specificity (95%) in comparison to MDCT. In addition, ROC analysis suggested that a peak velocity of N100 cm/s gives the best accuracy of detecting pulmonary vein stenosis. Noninvasive methods for detecting pulmonary vein stenosis include MDCT, MRI, and TEE where the gold standard is considered invasive retrograde venography. Recent guidelines do not recommend any imaging modality, including TEE, in the surveillance of pulmonary veins because of the limited number of studies.4,19 Both MDCT and MRI have been considered superior to TEE in the detection of pulmonary vein stenosis21 despite several studies showing higher incidence of detection of pulmonary vein stenosis in studies where TEE is used.10,11 Of interest, a study using invasive retrograde angiography for comparison with MDCT also showed that MDCT underestimates the incidence of pulmonary vein stenosis.22 Incidence of pulmonary vein stenosis may be determined by the ablation technique; and in the future, we may expect reduced incidence of pulmonary vein stenosis because of new approaches such as antral ablation with less ablation at the pulmonary ostia.7 However, large discrepancies in the imaging of pulmonary veins between techniques suggest that further comparison studies are needed. It should be pointed out that both techniques are approaching pulmonary vein stenosis differently. Multidetector computed tomography and MRI measure a loss of caliber of the pulmonary ostia compared to an adjacent segment, whereas TEE measures a pressure gradient across a stenosis, similar to mitral stenosis. In addition, the radiation associated with MDCT is of concern with the effective dose per study—estimated to be between 6.4 and 14.8 mSv.23 This amount of radiation is possibly associated with increased risk for cancer24 and, therefore, makes MDCT a less desirable option for serial imaging when compared to TEE and MRI.25 Currently, studies using TEE appear more sensitive in detecting pulmonary vein stenosis than studies using MDCT or MRI. Chen et al10 reported a 42% incidence of pulmonary vein stenosis and Arentz et al11 an incidence of 27% when using TEE for detection of pulmonary vein stenosis. The difference between the 2 studies might be explained by different cutoff values for abnormal pulmonary vein velocities, N8010 and 110 cm/s,11 respectively. In addition, Arentz et al11 assessed for turbulent flow within pulmonary veins for additional confirmation of stenosis. In the study of Arentz et al,11 there was an excellent agreement between MRI and TEE in 47 subjects. However, MRI underestimated the pulmonary vein stenosis in 1 subject and missed the diagnosis in another subject because of suboptimal image quality. Two recent prospective MRI studies reported the incidence of pulmonary vein stenosis as 18.1% and 2.8%.12,13 Recently, a CT study reported the incidence of pulmonary vein stenosis as

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0%.14 In our current study, the incidence of pulmonary vein stenosis was 5% by MDCT analysis and 11% by TEE analysis. When using TEE as the reference for detection of pulmonary vein stenosis, ROC analysis suggested that MDCT had a sensitivity of only 73% and a specificity 97% with area under the curve of 0.90 (Figure 3). The apparent lack of sensitivity of MDCT and MRI might be attributable to the need for ECG gating and motion artifacts in patients with atrial fibrillation. This lack of sensitivity might be overcome with the evaluation of physiologic consequences of the stenosis, which is possible with MRI but not with MDCT. Multidetector computed tomography requires other imaging modalities, such as ventilation-perfusion scanning of the lungs, to determine the physiologic consequences of pulmonary vein stenosis.16 Other very important benefits in using TEE are the lack of radiation associated with the technique and the ability to detect changes in vessel diameter and pulmonary vein velocities.26 A recent study has suggested using TEE during the initial step in a staged approach for detection of pulmonary vein stenosis, and that MDCT could be added if TEE yields insufficient results.27 Our study would support this staged approach because there was overall good concordance between the 2 imaging modalities. Significant stenosis by MDCT was not missed by TEE except for 1 patient (case 11, Table V). Of note, LUPV is the most readily assessable pulmonary vein, and underestimation of velocity due to poor angle is unlikely. It is therefore possible that the degree of stenosis was overestimated by MDCT. Figure 4 illustrates how stenosis in 1 patient by MDCT appears to be 70% in a single view, but by review of other images was judged to be 50%. In this patient, the peak velocity was N100 cm/s. When TEE detected pulmonary vein stenosis in our study, this was not always supported by the MDCT. Three pulmonary veins had peak velocities N100 cm/s by TEE; but MDCT analysis defined their stenosis as only 0% to 20%, and a number of pulmonary veins had 40% to 45% stenosis by MDCT and peak velocities of N100 cm/s (Table V). This could suggest that TEE might be more sensitive than MDCT in detecting pulmonary vein stenosis. Our study found that both left and right upper veins showed higher peak velocities than the lower veins. This may be because the angle of interrogation was often less optimal for the lower veins. Another factor could be the effect of gravity on pulmonary veins because the left lateral recumbent position could lead to decreased flow measurements in the right pulmonary veins.28 However, there was no difference in peak velocities in the left and right pulmonary veins in our study. Limitations of the current study include retrospective analysis, different TEE operators, and limited follow-up of subjects in many cases due to geographic distance. In our study, the average time to follow-up imaging was

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only 4 months; in contrast, in other studies pulmonary vein stenosis has been detected 6 to 12 months after ablation.29 Another limitation of this study is that we did not use invasive selective pulmonary venography as gold standard. Invasive retrograde venography of pulmonary veins carries a high risk of thromboembolic events and, in some cases, poorly defines the antrum of the pulmonary veins. In addition, the CT images are analyzed by using a 16-slice scanner (rather than the 64-slice scanner) from middiastolic phases, which might overestimate the degree of stenosis. Another limitation of our study is that we could not define with certainty all pulmonary veins by TEE. This might be explained by the multiple TEE operators and lack of identifying common antrum for upper and lower pulmonary veins.30 Also, pulmonary vein velocities during TEE may be influenced by shunting of flow away from a high stenotic vein to other venous drainage thus decreasing velocity. Conversely, a nonstenotic or minimally stenotic vein may theoretically receive extra flow from a stenotic vein thereby increasing its velocity. However, we do not think that this played a significant role in our findings. There is an ongoing prospective trial for detection of pulmonary vein stenosis by TEE after ablation called the ROTEA (role of transesophageal echocardiography in pulmonary vein ablation) study, where the goal is to better define the role of TEE and intracardiac echocardiography in comparison to MDCT.31,32

Conclusions There is concordance between MDCT and TEE for detecting pulmonary vein stenosis after pulmonary vein isolation for atrial fibrillation. Clinically significant pulmonary vein stenosis was detected by both modalities, where pulmonary veins may be visualized more frequently by MDCT, but TEE provides additional data about the functional significance of stenoses without subjecting patients to unnecessary radiation.

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21. Yang M, Akbari H, Reddy GP, et al. Identification of pulmonary vein stenosis after radiofrequency ablation for atrial fibrillation using MRI. J Comput Assist Tomogr 2001;25:34 - 5. 22. Burgstahler C, Trabold T, Kuettner A, et al. Visualization of pulmonary vein stenosis after radio frequency ablation using multi-slice computed tomography: initial clinical experience in 33 patients. Int J Cardiol 2005;102:287 - 91. 23. Hausleiter J, Meyer T, Hadamitzky M, et al. Radiation dose estimates from cardiac multislice computed tomography in daily practice: impact of different scanning protocols on effective dose estimates. Circulation 2006;113:1305 - 10. 24. Cohen BL. Cancer risk from low-level radiation. AJR Am J Roentgenol 2002;179:1137 - 43. 25. Thompson RC, Cullom SJ. Issues regarding radiation dosage of cardiac nuclear and radiography procedures. J Nucl Cardiol 2006;13:19 - 23. 26. Kinnaird TD, Uzun O, Munt BI, et al. Transesophageal echocardiography to guide pulmonary vein mapping and ablation for atrial fibrillation. J Am Soc Echocardiogr 2004;17:769 - 74. 27. Purerfellner H, Aichinger J, Martinek M, et al. Incidence, management, and outcome in significant pulmonary vein stenosis

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The following article is an AHJ Online Exclusive. Full text of this article is available at no charge at our website: www.ahjonline.com

Polytetrafluoroethylene graft calcification in patients with surgically repaired congenital heart disease: Evaluation using multidetector-row computed tomography Yasunobu Hayabuchi, MD,a Kazuhiro Mori, MD,a Tetsuya Kitagawa, MD,b Miho Sakata, MD,a and Shoji Kagami, MDa Tokushima, Japan

Background

Noninvasive determination of calcified prosthetic

ventricular outflow tract (RVOT) prosthesis, 2 of 8 (25%) for atrial septal

polytetrafluoroethylene (PTFE) is important in improving risk stratification.

patches of the Fontan procedure, and 7 of 7 (100%) for extracardiac

The purpose of this study is to assess the feasibility of multidetector-row

conduits of total cavopulmonary connection. The CT attenuation of PTFE

computed tomography (MDCT) for the evaluation of PTFE calcification in

revealed significantly different values for VSD patches (114 F 61 Hounsfield

patients with surgically repaired congenital heart disease and to

units [HU]), RVOT prosthesis (243 F 132 HU), atrial septal patches (163 F

evaluate the development and characteristics of calcification for specific

161 HU), and extracardiac conduits (230 F 29 HU) ( P b .0001). The CT

surgical procedures.

density value of VSD patches was significantly lower than those of RVOT

Methods

grafts and extracardiac conduits ( P b .05). The MDCT findings were

Seventy-six implanted PTFE grafts in 47 patients were

evaluated by MDCT (Aquillion 16, Toshiba Corporation, Tokyo, Japan).

consistent with histologic analysis in the evaluation of calcification.

Explanted PTFE grafts were evaluated histologically in 4 patients who

Conclusions

underwent reoperation after MDCT scans.

Results

Calcification of prosthetic PTFE was detected in 5 of 29 cases

(17%) for ventricular septal defect (VSD) patches, 26 of 32 (81%) for right

This study demonstrates that MDCT enables the

evaluation of prosthetic PTFE graft calcification; PTFE grafts in 4 different implantation sites demonstrated distinctive features and the prevalence of calcification. (Am Heart J 2007;153:806.e12806.e8.)