CLINICAL STUDY
Reperfusion Rates of Pulmonary Arteriovenous Malformations after Coil Embolization: Evaluation with Time-Resolved MR Angiography or Pulmonary Angiography Masashi Shimohira, MD, Tatsuya Kawai, MD, Takuya Hashizume, MD, Kengo Ohta, MD, Motoo Nakagawa, MD, Yoshiyuki Ozawa, MD, Keita Sakurai, MD, and Yuta Shibamoto, MD
ABSTRACT Purpose: To assess reperfusion rates after coil embolization for pulmonary arteriovenous malformations (PAVMs) using timeresolved magnetic resonance (MR) angiography or pulmonary angiography. Materials and Methods: Patients with PAVMs who underwent embolization and met the following inclusion criteria were included: (a) embolization was performed using bare or fibered platinum microcoils or both, (b) the complete cessation of flow was confirmed by digital subtraction angiography, and (c) follow-up examinations were conducted with time-resolved MR angiography or pulmonary angiography. Coil embolization was performed in 16 patients with 24 untreated or reperfused PAVMs. Sac embolization was performed for 12 untreated PAVMs. Feeding artery embolization was performed as primary embolization in each of the 12 reperfused PAVMs. Five PAVMs were treated 2 to 4 times because of reperfusion. The study included 32 coil embolizations. Follow-up images were reviewed, and reperfusion rates were assessed. The relationships between reperfusion and the location of PAVM, size of PAVM (feeding artery and venous sac), coils (number and total length), timing of embolization (primary or repeat embolization), and types of coils used (with or without fibered coils) were examined. Results: Reperfusion rates at 3, 6, 12, and 24 months were 8%, 27%, 36%, and 49%, respectively, for the 12 untreated PAVMs (primary embolization) and 50%, 50%, 92%, and 100%, respectively, for the 12 reperfused PAVMs (repeat embolization) (P ¼ .0062). No significant differences were observed in the other parameters measured. Conclusions: When evaluated with time-resolved MR angiography or pulmonary angiography, reperfusion rates after coil embolization for PAVM were considerably high, particularly with repeat embolization.
ABBREVIATIONS DSA = digital subtraction angiography, PAVM = pulmonary arteriovenous malformation
From the Department of Radiology, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi4678601, Japan. Received September 14, 2014; final revision received February 4, 2015; accepted February 18, 2015. Address correspondence to M.S.; E-mail: [email protected] None of the authors have identified a conflict of interest. Table E1 is available online at www.jvir.org. & SIR, 2015 J Vasc Interv Radiol 2015; 26:856–864 http://dx.doi.org/10.1016/j.jvir.2015.02.016
Pulmonary arteriovenous malformations (PAVMs) are direct connections between the pulmonary artery and vein through a thin-walled venous sac (1). Although PAVMs were historically treated with surgical resection, advances in endovascular techniques led to embolization becoming the mainstay of treatment. The indication for embolization needs to be evaluated for PAVMs with feeding arteries that are Z 3 mm in diameter because of the higher risk of paradoxical embolization and stroke associated with PAVMs of this size (2–4); however, more recent studies implied that this size should be Z 1 mm (5,6). Coils and detachable balloons were extensively used in PAVM embolization, and because there are
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currently no commercially available detachable balloons for the occlusion of PAVM, coils have become the main tool (7). Pulmonary angiography is considered the ideal imaging modality for reperfusion of a treated PAVM, but it is an invasive procedure (8). Although reperfusion rates ranging from 8% to 19% have been reported in the literature, all were obtained by measuring the size of the venous sac or draining vein by computed tomography (CT) (5,9–11). However, such an evaluation using CT merely provides an indirect finding, and a previous study showed that CT may not accurately reflect the status of PAVM after coil embolization (12). Time-resolved magnetic resonance (MR) angiography, which can depict blood flow by reperfusion, was recently reported to be a more useful option than CT for assessing the reperfusion of PAVM after coil embolization (13). The aim of the present study, which was performed at two institutions, was to assess retrospectively reperfusion rates after coil embolization for PAVM using time-resolved MR angiography or pulmonary angiography.
MATERIALS AND METHODS Patients This retrospective study was approved by the institutional review board. Written informed consent for the procedure was obtained from each patient. Requirements for inclusion in the study were as follows: (a) embolization was performed using bare or fibered coils or both, (b) complete cessation was confirmed by digital subtraction angiography (DSA) after embolization, and (c) patients had followup examinations with time-resolved MR angiography or pulmonary angiography. Coil embolization with 0.010- to 0.018-inch bare or fibered platinum microcoils, or both, was performed on 16 patients with untreated or reperfused PAVMs with feeding arteries Z 1 mm in diameter between May 2011 and August 2013; a diameter of 1 mm was selected because a 1-mm PAVM can cause septic emboli to enter the systemic circulation (5), and this diameter was sufficient for a theoretic treatment floor with a microcatheter (6). Three patients were men and 13 were women, and median age was 56 years (range, 16–81 y). Four patients had multiple PAVMs for a total of 24 PAVMs: 12 untreated PAVMs (primary embolization) and 12 reperfused PAVMs (second embolization). Sac embolization was performed for the 12 untreated PAVMs. Feeding artery embolization was performed as primary embolization in each of the 12 reperfused PAVMs. Repeated embolizations were performed because of reperfusion in three of the 12 untreated PAVMs (second embolization in three, third embolization in one) and four of the 12 reperfused PAVMs (third embolization in five, fourth embolization in three, fifth embolization in two, sixth embolization in one). The total number of procedures performed was 39 (12 primary embolizations, 15 second embolizations, six third embolizations, three
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fourth embolizations, two fifth embolizations, and one sixth embolization). Complete cessation could not be obtained in two procedures (one fourth embolization and one fifth embolization), and hydrophilic coils were attempted in four procedures (one second embolization, two third embolizations, one sixth embolization). One patient moved to another hospital and could not be followed (one third embolization). These procedures were excluded from this study, leaving 16 patients with 24 PAVMs and 32 procedures (12 primary embolizations, 14 second embolizations, three third embolizations, two fourth embolizations, one fifth embolizations) that were evaluated in this study. Follow-up images were interpreted by two radiologists (M.S. and T.K., with 12 and 10 years of experience, respectively, in diagnostic and interventional radiology), and reperfusion rates were evaluated. Any discrepancies were resolved by consensus.
Technique of Coil Embolization All procedures were reviewed and confirmed to have been performed in accordance with the technique described here. All procedures were approached via the femoral vein with a 5-F, 6-F, 7-F, or 8-F sheath (Super Sheath; Medikit, Tokyo, Japan). To prevent the formation of a thrombus during the procedure, 3,000 units (1,000 units/mL) of heparin was administered intravenously, with an additional 1,000 units being added every hour. A 5-F, 6-F, 7-F, or 8-F balloon catheter was introduced into the pulmonary artery. When a 7-F or 8F balloon catheter (Patlive; Terumo Clinical Supply, Gifu, Japan, or Optimo; Tokai Medical Products, Kasugai, Japan) was used, a 4-F multipurpose catheter (Terumo, Tokyo, Japan) was placed through the balloon lumen, and a microcatheter (Excelsior 1018; Stryker Neurovascular, Fremont, California, or MARVEL; Tokai Medical Products, or Rapid Transit; Cordis Endovascular Systems, Miami Lakes, Florida) was then placed through the 4-F catheter. When a 5-F or 6-F balloon catheter (Serecon MP catheter II; Terumo, or Balloon Angiographic Catheter; Harmac Medical Products, Buffalo, New York) was used, the same microcatheters were placed through the balloon catheter lumen. Usually, the larger balloon catheters were selected because the 4-F coaxial catheter contributes to additional support for the microcatheter and embolization. Choice of a balloon catheter was based on size and tortuosity of the feeding artery. The microcatheter was inserted into the venous sac for untreated PAVMs, and embolization of the venous sac and the feeding artery was performed. For reperfused PAVMs, the microcatheter was inserted into the interstices of the original coils of the feeding artery as deeply as possible, and embolization of the inside of the original coil pack and feeding artery was performed. Coil embolization was performed using bare coils (IDC; Stryker Neurovascular, or GDC; Stryker Neurovascular, or Cerecyte coil; Micrus
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Endovascular, San Jose, California, or DETACH; Cook, Inc, Bloomington, Indiana) or fibered coils (Interlock; Stryker Neurovascular, or Tornado; Cook, Inc), or both, with inflation of the balloon to prevent coil migration. Saline flush was used during coil embolization to prevent thrombus formation inside the catheters.
Follow-up Examinations for Reperfusion Time-resolved MR angiography was the planned imaging follow-up procedure with examinations at 1–3 months, 5– 7 months, and every 6–12 months thereafter. On timeresolved MR angiography, reperfusion was defined as simultaneous enhancement of the feeding artery and draining vein or enhancement of the venous sac in the pulmonary arterial phase (before visualization of the normal pulmonary vein) (13). When reperfusion was diagnosed, repeat embolization was recommended. However, in patients with multiple PAVMs, embolization of all could not be accomplished in a single session, and PAVMs that had received embolization previously were evaluated by pulmonary angiography instead of time-resolved MR angiography during subsequent embolization sessions. Pulmonary angiography was performed only in such additional embolization cases. Additional embolization sessions were planned 2–5 months after the first session. When pulmonary angiography was performed from the main right or left pulmonary artery, a power injector was always used, and when it was performed from the feeding artery of the PAVM, contrast material was manually injected. Reperfusion was defined as simultaneous enhancement of the feeding artery and draining vein or the venous sac (8).
Image Acquisition and Reconstruction of Time-Resolved MR Angiography All studies were performed on a 1.5-tesla MR system (Achieva; Philips Healthcare, Best, The Netherlands) or 3.0-tesla system (Skyra; Siemens AG Medical Systems, Forchheim, Germany) using a five-element cardiac surface coil or an 18-element body coil, respectively. Timeresolved MR angiography was acquired with a threedimensional MR angiography T1-weighted fast-field echo sequence with the following parameters: for Achieva, repetition time/echo time ¼ 4.7/1.4 ms, flip angle ¼ 401, field of view ¼ 400 mm with 80% rectangular field of view, matrix ¼ 336 227, slice thickness ¼ 3 mm interpolated to 1.5 mm, and 25 slices acquired to cover a slab thickness of 37.5 mm; for Skyra, repetition time/echo time ¼ 2.1/0.9 ms, flip angle ¼ 101, field of view ¼ 430 mm, matrix 320 320, slice thickness ¼ 1.5 mm, and 40 slices acquired to cover a slab thickness of 60.0 mm. To reduce the number of inplane phase-encoding steps, parallel imaging and keyhole imaging techniques were applied with factors of 2.5 and 20%, respectively, for Achieva and factors of 3 and 10%, respectively, for Skyra, achieving temporal
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resolutions of 1.7 seconds and 1.0 second, respectively. Each slab was set to include the feeding artery, draining vein, and venous sac with portions of the aorta, main pulmonary artery, and left atrium to detect the temporal phase. There were 25 three-dimensional volumes acquired consecutively after a 5.0-second reference scan under breath-holding conditions. Data acquisition began simultaneously with a contrast medium injection (0.1 mmol/kg of gadolinium chelate [Magnevist; Bayer HealthCare Pharmaceuticals, Whippany, New Jersey]) at a flow rate of 2 mL/s, followed by a saline flush of 30 mL during breath-holding. All source images from each frame were reconstructed with a maximum intensity projection algorithm.
Statistical Analysis Differences in the location of PAVM, size of PAVM, and amount of coils in the two groups (nonreperfused and reperfused) were examined by χ2 test or t test. Reperfusion rates were calculated by the Kaplan-Meier method, and differences between the two groups, primary embolization versus repeat embolization and with versus without fibered coils, were examined by the logrank test. P o .05 was considered to indicate a significant difference. All statistical analyses were carried out using GraphPad Prism (GraphPad Software, Inc, La Jolla, California).
RESULTS Details of the PAVMs treated in the present study are summarized in Table 1. There were 23 PAVMs with a single feeding artery (simple type), and one PAVM had multiple feeding arteries (complex type). The results of each procedure included in this study are shown in Table E1 (available online at www.jvir.org), and details of the examinations conducted after these procedures are summarized in Figure 1. Only pulmonary angiography was performed for the 12 procedures on six PAVMs in one patient. Time-resolved MR angiography was initially Table 1 . Details of 24 PAVMs that Were the First Procedure at the Time of Entry in the Study Location RUL/RML/RLL/LUL/LLL
2/6/5/3/8
Size* Feeding artery (mm)
3.8 (1.4–5.2)
Venous sac (mm)
7 (2.8–26.6)
Type Simple/complex
23/1
Timing Primary/repeat
12/12
LLL ¼ left lower lobe, LUL ¼ left upper lobe, PAVM ¼ pulmonary arteriovenous malformation, RLL ¼ right lower lobe, RML ¼ right middle lobe, RUL ¼ right upper lobe. *Median (range).
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performed for the other 20 procedures on 18 PAVMs in 15 patients, and pulmonary angiography was performed for six procedures on six PAVMs in four patients. The remaining 14 procedures on 14 PAVMs in 12 patients were followed with time-resolved MR angiography only (one patient number and one PAVM number were duplicated in “time-resolved MR angiography and pulmonary angiography” and “time-resolved MR angiography only”; patient no. 16, PAVM no. 24 in Table E1 [available online at www.jvir.org]). In this study, seven of 24 PAVMs in seven patients were occluded, and the remaining 17 PAVMs in 11 patients were reperfused (two patients were duplicated in occluded PAVM and reperfused PAVM; patient no. 14 and patient no. 15 in Table E1, Figs 2a–e, 3a–d). We attempted embolization of two reperfused PAVMs (PAVM no. 2 and PAVM no. 3 in Table E1) in one patient but did not achieve complete cessation because of the lack of a margin for embolization; this indicated that the residual proximal feeder vessel length was insufficient, which may have caused the reflux of coils into normal pulmonary arterial branches when coil embolization was attempted (12). The other two reperfused PAVMs (PAVM no. 5 and PAVM no. 6 in Table E1) in the same patient also appeared to have no margin for embolization by pulmonary angiography and were observed. Paradoxical embolization has not yet occurred in this patient. Repeat embolization with hydrophilic coils was performed in four reperfused PAVMs (PAVM no. 1, PAVM no. 4, PAVM no. 18, and PAVM no. 22 in Table E1) in three patients, and repeat embolization with bare coils was performed in one reperfused PAVM (PAVM no. 12 in Table E1) in one patient; however, this patient moved to another hospital and could not be followed. The remaining eight reperfused PAVMs in seven patients were observed with timeresolved MR angiography because the patients did not agree to undergo repeat embolization. The reason for refusal was uncertainty to acquire complete occlusion with
Figure 1. Chart of follow-up examinations after procedures. PAG ¼ pulmonary angiography, TR-MRA ¼ time-resolved MR angiography. *PAG findings were in accordance with TR-MRA findings in all cases.
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the next procedure. Paradoxical embolization has not yet occurred. In all 16 patients, the follow-up period was defined as the interval between the first embolization procedure and last follow-up visit. The median follow-up period was 24 months (range, 1–39 mo). Two patients who did not have reperfusion were lost at 1 month (first follow-up) and 7 months (second follow-up), respectively, and the remaining 14 patients have had continuous follow-up evaluations. Of the 14 patients, 5 had less than a 24month follow-up period (median, 20 mo; range, 10–23 mo). The median periods of first, second, third, fourth, fifth, and sixth follow-up examinations were 2, 7, 14, 17, 19, and 21.5 months after coil embolization. In 25 of 32 procedures, reperfusion was detected at a median interval of 5 months (range, 1–18 mo), and there was no reperfusion in 7 procedures with a median interval of 20 months (range, 1–25 mo). Of the 25 reperfusions, 24 occurred because of recanalization through previously placed coils, and 1 was attributed to the development of an accessory pulmonary arterial feeder vessel, even though eight of 24 cases of recanalization through previously placed coils were evaluated with time-resolved MR angiography only. Bronchial artery hypertrophy was not detected in any patient, even in PAVM cases evaluated with time-resolved MR angiography only. In 24 PAVMs, the median size of the feeding artery was 3.8 mm (range, 1.4–5.2 mm), and the median size of the venous sac was 7 mm (range, 2.8–26.6 mm). The median number of coils was 10 (range, 3–57), and the median length of all coils used was 82 cm (range, 20– 1,455 cm). Details regarding the PAVM location and size and coils used in the nonreperfused and reperfused groups based on PAVMs are summarized in Table 2. No significant differences were observed between the two groups in any of these parameters. The reperfusion rates of primary embolization and repeat embolization were compared. In the 24 PAVMs, the 3month, 6-month, 12-month, and 24-month reperfusion rates were 8%, 27%, 36%, and 49%, respectively, for the 12 untreated PAVMs (primary embolization) and 50%, 50%, 92%, and 100%, respectively for the 12 reperfused PAVMs (repeat embolization) (P ¼ .0062) (Fig 4). In all 32 procedures, the 3-month, 6-month, 12-month, and 24month reperfusion rates were 8%, 27%, 36%, and 49%, respectively, for the 12 primary embolization procedures and 45%, 65%, 95%, and 100%, respectively, for the 20 repeat embolization procedures (P ¼ .0011). The reperfusion rates after the second embolization versus the third, fourth, or fifth embolization were as follows: the 3-month, 6-month, 12-month, and 24-month reperfusion rates were 50%, 50%, 93%, and 100%, respectively, for the 14 second embolization procedures and 33%, 100%, 100%, and 100%, respectively, for the six third, fourth, or fifth embolization procedures (P ¼ .22). The reperfusion rates of embolization evaluated with or without fibered coils were compared. Coil embolization
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Figure 2. A 53-year-old woman presented with reperfused PAVM of the left lower lobe. Reperfusion was suspected on a CT scan, and pulmonary angiography was performed 65 months after primary embolization. (a) Angiography from the feeding artery (arrowhead) at primary embolization shows PAVM in the left lower lobe (arrow). (b) Angiography from inside of the original coils of the feeding artery (arrowhead) performed 65 months after primary embolization shows reperfusion (arrow). A second embolization was performed. (c) Angiography from the feeding artery performed after 2 months shows reperfusion (arrow). A third embolization was performed. (d) Angiography from the left pulmonary artery performed after 4 months shows reperfusion (arrow). A fourth embolization was performed. (e) Angiography from the left pulmonary artery after 5 months shows reperfusion (arrow). Because there was no margin to place coils, embolization could not be performed.
was performed with bare coils only in 12 PAVMs, with fibered coils only in one PAVM, and with both bare and fibered coils in 11 PAVMs. Fibered coils were used in 12 of the 24 PAVMs. The 3-month, 6-month, 12-month, and 24-month reperfusion rates were 50%, 58%, 83%, and 92%, respectively, in 12 PAVMs with embolization without fibered coils and 8%, 18%, 48%, and 60%, respectively, in 12 PAVMs with embolization with fibered coils (P ¼ .063) (Fig 5).
DISCUSSION Follow-up examinations after successful coil embolization are important for detecting reperfusion, and DSA is the most sensitive modality used to examine blood flow through lesions because it detects simultaneous enhancements in the feeding artery and draining vein
in reperfused PAVMs (8). In occluded PAVMs, as in normal pulmonary vessels, enhancements in the vein have been shown to occur within a few seconds of visualizing the artery (8). However, because DSA is an invasive follow-up examination, CT has been routinely performed. The reperfusion rates evaluated by CT were previously reported to be up to 19% (9–12). However, the CT criteria reported in the literature included the complete, or at least a 70%, reduction in a draining vein and venous sac or their contrast enhancements; CT is considered to provide only an indirect finding (1,8– 12,14). Difficulties have been associated with evaluating CT images because of image deterioration secondary to metal artifacts generated by the coils (8,9,15). Time-resolved MR angiography has become a valuable option as an alternative to DSA for screening after coil embolization because of its high sensitivity in detecting flow and the absence of ionizing radiation,
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Figure 3. A 72-year-old woman presented with untreated PAVM of the left lower lobe. (a) Angiography of the left pulmonary artery shows PAVM in the left lower lobe (arrow). (b) Angiography after coil embolization shows complete occlusion of PAVM. (c) Timeresolved MR angiography performed 1 month after coil embolization shows slight blood flow from the PAVM (arrow), leading to a diagnosis of reperfusion. (d) Angiography performed 2 months after coil embolization shows slight reperfusion (arrow). Repeat embolization was performed.
and it offers a noninvasive examination with high resolution (16). Platinum coils, which have relatively low paramagnetic characteristics, are known to produce very few artifacts in MR imaging (13,17,18), and only platinum coils were used in this study. Kawai et al (13) reported the usefulness of time-resolved MR angiography over CT in diagnosing the reperfusion of PAVM after coil embolization. They demonstrated that timeresolved MR angiography displayed high diagnostic
specificity, positive predictive values, and sensitivity, and these values were in marked contrast to values obtained using CT. In the present study, reperfusion was evaluated using time-resolved MR angiography or pulmonary angiography, both of which can depict blood flow by reperfusion, and reperfusion rates were markedly higher than rates reported in the literature. Recognizing high reperfusion rates and how to decrease them is of clinical importance.
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Table 2 . Details of PAVM Location and Size and Coils in Nonreperfused and Reperfused Groups Based on PAVMs Nonreperfused (n ¼ 7)
Reperfused (n ¼ 17)
P
Location 0/1/1/2/3
2/5/4/1/5
.43
Size of PAVM* Feeding artery (mm)
RUL/RML/RLL/LUL/LLL
3 (2–4)
3.8 (1.4–5.2)
.12
Venous sac (mm)
4.6 (2.8–15.5)
7 (3.9–26.6)
.50
12 (3–23)
10 (4–57)
.98
129 (28–182)
72 (20–1,455)
.72
Coils* Number of coils Total length (cm)
LLL ¼ left lower lobe, LUL ¼ left upper lobe, PAVM ¼ pulmonary arteriovenous malformation, RLL ¼ right lower lobe, RML ¼ right middle lobe, RUL ¼ right upper lobe. *Median (range).
Figure 4. Reperfusion curves in the two groups undergoing primary embolization and repeat embolization. The reperfusion rate was significantly higher in the repeat embolization group (P ¼ .0062).
Embolization of the feeding artery and the venous sac was previously shown to prevent reperfusion (1,19), and our primary embolization was performed according to this method in the present study. However, the reperfusion rates of primary embolization were higher; the 3month, 6-month, 12-month, and 24-month reperfusion rates for the 12 primary embolization procedures were 8%, 27%, 36%, and 49%, respectively. Reperfusion rates were markedly worse with repeat embolization; the 3month, 6-month, 12-month, and 24-month reperfusion rates were 50%, 50%, 92%, and 100%, respectively. The sensitivity of time-resolved MR angiography appears to be very high, allowing even slightly reperfused flow to be detected. We speculated that the risk of paradoxical embolization may be decreased when the amount of blood flow in the right-to-left shunt decreases. However, the risk may not be zero because symptomatic paradoxical embolization was reported in patients with only sub-3-mm feeding arteries (20,21), even though the indication for PAVM embolization used to be a feeding artery Z 3 mm (6). Shovlin et al (22) stated that the size of PAVM did not predict the risk of brain abscesses and ischemic stroke. However, Lee et al (23) reported that contrast echocardiography was positive in 79% of patients after successful embolization, and they suspected that these patients may have small PAVMs
Figure 5. Reperfusion curves in the two groups undergoing embolization with and without fibered coils. No significant differences were observed in reperfusion rates between the two groups (P ¼ .063).
that were undetectable by pulmonary angiography. These authors considered whether such very small PAVMs were clinically relevant. It is uncertain at the present time whether slight reperfusion detected with time-resolved MR angiography is clinically relevant, and it is difficult to determine the amount of reperfusion flow that is considered clinically problematic. This issue needs to be examined in more detail in a larger study, in which how much flow of the reperfusion is relevant should be investigated by carefully observing patients with reperfusion who refuse repeat embolization. Lee et al (9) reported that interim ischemic strokes occurred in two of eight patients with persistent PAVMs. Repeat embolization for reperfusion has been reported previously (9,12,24), and we consider retreatment to be necessary for reperfusion. Repeat embolization is recommended in our hospital, and patients who refused this treatment were observed. However, reperfusion rates with repeat embolization were worse than rates with primary embolization in the present study. Although the complete cessation of reperfusion is obtained at the end of the repeat embolization procedure, more coils may need to be placed into the feeding artery. Fibered coils were previously shown to produce thrombosis more effectively than bare coils (25), and reperfusion rates with or without fibered coils were assessed. Although no significant difference was observed, the P value was
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.063; embolization without fibered coils may cause reperfusion more than embolization with fibered coils. The most common mechanism underlying reperfusion is recanalization through previously placed coils (12,15), and this is generally considered to occur because of the elongation of coils or an insufficient number of coils, both of which may cause a failure in the formation of a thrombus (26). Tight embolization is important for preventing coil elongation. Although we performed coil embolization as tightly as possible in all cases in the present study, our reperfusion rate was still high. We assumed that coil elongation could not be completely prevented when coil embolization was performed. An AMPLATZER vascular plug (St Jude Medical, Inc, St Paul, Minnesota) was reported as a useful material for PAVM with low recanalization rates (up to 7%) (14,27). The use of a hydrophilic coil in embolization for cerebral aneurysm has been shown to prevent recanalization (28,29). Hydrophilic coils are made of platinum helical coils coated with a layer of hydrophilic acrylic polymer (hydrogel), which, on contact with blood, causes the disentanglement of polymer chains and expansion (30). It contributes to a higher packing density and lower thromboembolic rate (31). In Japan, health insurance coverage of AMPLATZER vascular plugs and hydrophilic coils is only more recent; the usefulness of these embolic materials for PAVM needs to be examined with time-resolved MR angiography in future studies. The reperfusion of PAVM after coil embolization may have been due not only to technical issues but also to the characteristics of the pulmonary artery. The pulmonary and systemic circulatory systems transport an equal amount of blood; however, the pulmonary circulation operates at markedly lower pressures than the systemic circulation. Pulmonary pressure is lower because resistance is lower, and the pulmonary vasculature is more compliant, and this compliance has been attributed to arterial wall elasticity and vessel size (32). We speculated that this high compliance made the pulmonary artery distend after coil embolization, leading to coil elongation. Our study has several limitations. The small sample size and retrospective design were key limitations. The time-resolved MR angiography equipment varied among patients, as did spatial and temporal resolutions. Although the 3.0-tesla MR system was superior to the 1.5-tesla MR system in these points, we considered it possible to obtain sufficient resolution to diagnose reperfusion even with 1.5-tesla MR. It was also difficult to measure the technical outcomes of coil embolization, even though complete cessation was confirmed by DSA after embolization. However, this measurement may be possible if the packing ratio of coils is calculated, similar to the embolization of an aneurysm (33), and coil placement is continued until a defined ratio even after complete cessation is confirmed. In addition, 20 procedures were evaluated with time-resolved MR
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angiography. Pulmonary angiography was performed after time-resolved MR angiography in six of these procedures, and consistency among the results obtained was confirmed. However, pulmonary angiography was not performed after the other 14 time-resolved MR angiography scans. Time-resolved MR angiography findings in 14 cases were not confirmed by pulmonary angiography. In previous studies, 0.035-inch coils were used, and reperfusion rates were lower than rates in the present study (10,15,34). However, microcoils were used in all procedures in this study, which may have contributed to the higher reperfusion rates. Future studies are warranted to clarify this issue. Another limitation is that the follow-up period was relatively shorter than that in the literature. However, our reperfusion rates were high even with the short follow-up period, which was an important finding. In conclusion, reperfusion rates after coil embolization for PAVM were higher than rates previously reported when an evaluation of reperfusion with time-resolved MR angiography or pulmonary angiography was performed. Further studies are needed to investigate longterm outcomes with a larger study cohort.
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malformations treated with embolization with platinum coils. J Vasc Interv Radiol 2014; 25:1339–1347. Letourneau-Guillon L, Faughnan ME, Soulez G, et al. Embolization of pulmonary arteriovenous malformations with amplatzer vascular plugs: safety and midterm effectiveness. J Vasc Interv Radiol 2010; 21: 649–656. Pollak JS, Saluja S, Thabet A, et al. Clinical and anatomic outcomes after embolotherapy of pulmonary arteriovenous malformations. J Vasc Interv Radiol 2006; 17:35–44. Spilberg G, Carniato SL, King RM, et al. Temporal evolution of susceptibility artifacts from coiled aneurysms on MR angiography: an in vivo canine study. AJNR Am J Neuroradiol 2012; 33:655–660. Koganemaru M, Abe T, Uchiyama D, et al. Detection of neck recanalization with follow-up contrast-enhanced MR angiography after renal artery aneurysm coil embolization. J Vasc Interv Radiol 2010; 21: 298–300. Koganemaru M, Abe T, Nonoshita M, et al. Follow-up of true visceral artery aneurysm after coil embolization by three-dimensional contrastenhanced MR angiography. Diagn Interv Radiol 2014; 20:129–135. Kajiwara K, Urashima M, Yamagami T, et al. Venous sac embolization of pulmonary arteriovenous malformation: safety and effectiveness at midterm follow-up. Acta Radiol 2014; 55:1093–1098. Trerotola S, Bernhardt B, Pyeritz R. Outpatient single-session pulmonary arteriovenous malformation embolization. J Vasc Interv Radiol 2009; 20:1287–1291. Todo K, Moriwaki H, Higashi M, et al. A small pulmonary arteriovenous malformation as a cause of recurrent brain embolism. AJNR Am J Neuroradiol 2004; 25:428–430. Shovlin CL, Jackson JE, Bamford KB, et al. Primary determinants of ischaemic stroke/brain abscess risks are independent of severity of pulmonary arteriovenous malformations in hereditary haemorrhagic telangiectasia. Thorax 2008; 63:259–266. Lee WL, Graham AF, Pugash RA, et al. Contrast echocardiography remains positive after treatment of pulmonary arteriovenous malformations. Chest 2003; 123:351–358.
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24. Woodward CS, Pyeritz RE, Chittams JL, et al. Treated pulmonary arteriovenous malformations: patterns of persistence and associated retreatment success. Radiology 2013; 269:919–926. 25. Graves VB, Partington CR, Rüfenacht DA, et al. Treatment of carotid artery aneurysms with platinum coils: an experimental study in dogs. AJNR Am J Neuroradiol 1990; 11:249–252. 26. Sagara K, Miyazono N, Inoue H, et al. Recanalization after coil embolotherapy of pulmonary arteriovenous malformations: study of long-term outcome and mechanism for recanalization. AJR Am J Roentgenol 1998; 170:727–730. 27. Tapping CR, Ettles DF, Robinson GJ. Long-term follow-up of treatment of pulmonary arteriovenous malformations with AMPLATZER Vascular Plug and AMPLATZER Vascular Plug II devices. J Vasc Interv Radiol 2011; 22:1740–1746. 28. White PM, Lewis SC, Gholkar A, et al. Hydrogel-coated coils versus bare platinum coils for the endovascular treatment of intracranial aneurysms (HELPS): a randomised controlled trial. Lancet 2011; 377:1655–1662. 29. Gunnarsson T, Tong FC, Klurfan P, et al. Angiographic and clinical outcomes in 200 consecutive patients with cerebral aneurysm treated with hydrogel-coated coils. AJNR Am J Neuroradiol 2009; 30:1657–1664. 30. Cantón G, Levy DI, Lasheras JC. Changes in the intraaneurysmal pressure due to HydroCoil embolization. AJNR Am J Neuroradiol 2005; 26:904–907. 31. White PM, Lewis SC, Nahser H, et al. HydroCoil Endovascular Aneurysm Occlusion and Packing Study (HELPS trial): procedural safety and operatorassessed efficacy results. AJNR Am J Neuroradiol 2008; 29:217–223. 32. Saouti N, Westerhof N, Postmus PE, Vonk-Noordegraaf A. The arterial load in pulmonary hypertension. Eur Respir Rev 2010; 19:197–203. 33. Yasumoto T, Osuga K, Yamamoto H, et al. Longterm outcomes of coil packing for visceral aneurysms: correlation between packing density and incidence of coil compaction or recanalization. J Vasc Interv Radiol 2013; 24:1798–1807. 34. Andersen PE, Kjeldsen AD. Clinical and radiological long-term follow-up after embolization of pulmonary arteriovenous malformations. Cardiovasc Intervent Radiol 2006; 29:70–74.
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Table E1 . Results of Each Procedure Included in Study Results of Each Procedure Patient No.
Second
Third
Fourth
Fifth
1
○
○
○
○
2 3
○ ○
○ ○
○
4 5 6 2 3 4
1
PAVM No.
First
Final Outcome
Strategy/Status at Reperfusion
Reperfused
Embolization with hydrophilic coils
Reperfused Reperfused
Complete cessation not obtained Complete cessation not obtained
○
Reperfused
Embolization with hydrophilic coils
○ ○
Reperfused Reperfused
No margin for embolization No margin for embolization
7
□
Reperfused
Observation
8 9
□ □
Reperfused Reperfused
Observation Observation
5
10
□
Reperfused
Observation
6 7
11 12
□ □○
Reperfused Reperfused
Observation Follow-up at another hospital
8
13
■
Occluded
—
9 10
14 15
■ ■
Occluded Occluded
— —
11
16
■
Occluded
—
12 13
17 18
■ □○
Occluded Reperfused
— Embolization with hydrophilic coils
14
19
■
Occluded
—
15
20 21
□ ■●
Reperfused Occluded
Observation —
22
□○
Reperfused
Embolization with hydrophilic coils
23 24
□ □○
Reperfused Reperfused
Observation Observation
16
□○
□
□ ¼ reperfusion diagnosed with time-resolved MR angiography performed, ■ ¼ no reperfusion diagnosed with time-resolved MR angiography performed, ○ ¼ reperfusion diagnosed with pulmonary angiography, ● ¼ no reperfusion diagnosed with pulmonary angiography, PAVM = pulmonary arteriovenous malformation.
Reperfusion Rates of Pulmonary Arteriovenous Malformations after Coil Embolization: Evaluation with Time-Resolved MR Angiography or Pulmonary Angiography Masashi Shimohira, MD, Tatsuya Kawai, MD, Takuya Hashizume, MD, Kengo Ohta, MD, Motoo Nakagawa, MD, Yoshiyuki Ozawa, MD, Keita Sakurai, MD, and Yuta Shibamoto, MD
ABSTRACT Purpose: To assess reperfusion rates after coil embolization for pulmonary arteriovenous malformations (PAVMs) using timeresolved magnetic resonance (MR) angiography or pulmonary angiography. Materials and Methods: Patients with PAVMs who underwent embolization and met the following inclusion criteria were included: (a) embolization was performed using bare or fibered platinum microcoils or both, (b) the complete cessation of flow was confirmed by digital subtraction angiography, and (c) follow-up examinations were conducted with time-resolved MR angiography or pulmonary angiography. Coil embolization was performed in 16 patients with 24 untreated or reperfused PAVMs. Sac embolization was performed for 12 untreated PAVMs. Feeding artery embolization was performed as primary embolization in each of the 12 reperfused PAVMs. Five PAVMs were treated 2 to 4 times because of reperfusion. The study included 32 coil embolizations. Follow-up images were reviewed, and reperfusion rates were assessed. The relationships between reperfusion and the location of PAVM, size of PAVM (feeding artery and venous sac), coils (number and total length), timing of embolization (primary or repeat embolization), and types of coils used (with or without fibered coils) were examined. Results: Reperfusion rates at 3, 6, 12, and 24 months were 8%, 27%, 36%, and 49%, respectively, for the 12 untreated PAVMs (primary embolization) and 50%, 50%, 92%, and 100%, respectively, for the 12 reperfused PAVMs (repeat embolization) (P ¼ .0062). No significant differences were observed in the other parameters measured. Conclusions: When evaluated with time-resolved MR angiography or pulmonary angiography, reperfusion rates after coil embolization for PAVM were considerably high, particularly with repeat embolization.
ABBREVIATIONS DSA = digital subtraction angiography, PAVM = pulmonary arteriovenous malformation
From the Department of Radiology, Nagoya City University Graduate School of Medical Sciences, 1, Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi4678601, Japan. Received September 14, 2014; final revision received February 4, 2015; accepted February 18, 2015. Address correspondence to M.S.; E-mail: [email protected] None of the authors have identified a conflict of interest. Table E1 is available online at www.jvir.org. & SIR, 2015 J Vasc Interv Radiol 2015; 26:856–864 http://dx.doi.org/10.1016/j.jvir.2015.02.016
Pulmonary arteriovenous malformations (PAVMs) are direct connections between the pulmonary artery and vein through a thin-walled venous sac (1). Although PAVMs were historically treated with surgical resection, advances in endovascular techniques led to embolization becoming the mainstay of treatment. The indication for embolization needs to be evaluated for PAVMs with feeding arteries that are Z 3 mm in diameter because of the higher risk of paradoxical embolization and stroke associated with PAVMs of this size (2–4); however, more recent studies implied that this size should be Z 1 mm (5,6). Coils and detachable balloons were extensively used in PAVM embolization, and because there are
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currently no commercially available detachable balloons for the occlusion of PAVM, coils have become the main tool (7). Pulmonary angiography is considered the ideal imaging modality for reperfusion of a treated PAVM, but it is an invasive procedure (8). Although reperfusion rates ranging from 8% to 19% have been reported in the literature, all were obtained by measuring the size of the venous sac or draining vein by computed tomography (CT) (5,9–11). However, such an evaluation using CT merely provides an indirect finding, and a previous study showed that CT may not accurately reflect the status of PAVM after coil embolization (12). Time-resolved magnetic resonance (MR) angiography, which can depict blood flow by reperfusion, was recently reported to be a more useful option than CT for assessing the reperfusion of PAVM after coil embolization (13). The aim of the present study, which was performed at two institutions, was to assess retrospectively reperfusion rates after coil embolization for PAVM using time-resolved MR angiography or pulmonary angiography.
MATERIALS AND METHODS Patients This retrospective study was approved by the institutional review board. Written informed consent for the procedure was obtained from each patient. Requirements for inclusion in the study were as follows: (a) embolization was performed using bare or fibered coils or both, (b) complete cessation was confirmed by digital subtraction angiography (DSA) after embolization, and (c) patients had followup examinations with time-resolved MR angiography or pulmonary angiography. Coil embolization with 0.010- to 0.018-inch bare or fibered platinum microcoils, or both, was performed on 16 patients with untreated or reperfused PAVMs with feeding arteries Z 1 mm in diameter between May 2011 and August 2013; a diameter of 1 mm was selected because a 1-mm PAVM can cause septic emboli to enter the systemic circulation (5), and this diameter was sufficient for a theoretic treatment floor with a microcatheter (6). Three patients were men and 13 were women, and median age was 56 years (range, 16–81 y). Four patients had multiple PAVMs for a total of 24 PAVMs: 12 untreated PAVMs (primary embolization) and 12 reperfused PAVMs (second embolization). Sac embolization was performed for the 12 untreated PAVMs. Feeding artery embolization was performed as primary embolization in each of the 12 reperfused PAVMs. Repeated embolizations were performed because of reperfusion in three of the 12 untreated PAVMs (second embolization in three, third embolization in one) and four of the 12 reperfused PAVMs (third embolization in five, fourth embolization in three, fifth embolization in two, sixth embolization in one). The total number of procedures performed was 39 (12 primary embolizations, 15 second embolizations, six third embolizations, three
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fourth embolizations, two fifth embolizations, and one sixth embolization). Complete cessation could not be obtained in two procedures (one fourth embolization and one fifth embolization), and hydrophilic coils were attempted in four procedures (one second embolization, two third embolizations, one sixth embolization). One patient moved to another hospital and could not be followed (one third embolization). These procedures were excluded from this study, leaving 16 patients with 24 PAVMs and 32 procedures (12 primary embolizations, 14 second embolizations, three third embolizations, two fourth embolizations, one fifth embolizations) that were evaluated in this study. Follow-up images were interpreted by two radiologists (M.S. and T.K., with 12 and 10 years of experience, respectively, in diagnostic and interventional radiology), and reperfusion rates were evaluated. Any discrepancies were resolved by consensus.
Technique of Coil Embolization All procedures were reviewed and confirmed to have been performed in accordance with the technique described here. All procedures were approached via the femoral vein with a 5-F, 6-F, 7-F, or 8-F sheath (Super Sheath; Medikit, Tokyo, Japan). To prevent the formation of a thrombus during the procedure, 3,000 units (1,000 units/mL) of heparin was administered intravenously, with an additional 1,000 units being added every hour. A 5-F, 6-F, 7-F, or 8-F balloon catheter was introduced into the pulmonary artery. When a 7-F or 8F balloon catheter (Patlive; Terumo Clinical Supply, Gifu, Japan, or Optimo; Tokai Medical Products, Kasugai, Japan) was used, a 4-F multipurpose catheter (Terumo, Tokyo, Japan) was placed through the balloon lumen, and a microcatheter (Excelsior 1018; Stryker Neurovascular, Fremont, California, or MARVEL; Tokai Medical Products, or Rapid Transit; Cordis Endovascular Systems, Miami Lakes, Florida) was then placed through the 4-F catheter. When a 5-F or 6-F balloon catheter (Serecon MP catheter II; Terumo, or Balloon Angiographic Catheter; Harmac Medical Products, Buffalo, New York) was used, the same microcatheters were placed through the balloon catheter lumen. Usually, the larger balloon catheters were selected because the 4-F coaxial catheter contributes to additional support for the microcatheter and embolization. Choice of a balloon catheter was based on size and tortuosity of the feeding artery. The microcatheter was inserted into the venous sac for untreated PAVMs, and embolization of the venous sac and the feeding artery was performed. For reperfused PAVMs, the microcatheter was inserted into the interstices of the original coils of the feeding artery as deeply as possible, and embolization of the inside of the original coil pack and feeding artery was performed. Coil embolization was performed using bare coils (IDC; Stryker Neurovascular, or GDC; Stryker Neurovascular, or Cerecyte coil; Micrus
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Endovascular, San Jose, California, or DETACH; Cook, Inc, Bloomington, Indiana) or fibered coils (Interlock; Stryker Neurovascular, or Tornado; Cook, Inc), or both, with inflation of the balloon to prevent coil migration. Saline flush was used during coil embolization to prevent thrombus formation inside the catheters.
Follow-up Examinations for Reperfusion Time-resolved MR angiography was the planned imaging follow-up procedure with examinations at 1–3 months, 5– 7 months, and every 6–12 months thereafter. On timeresolved MR angiography, reperfusion was defined as simultaneous enhancement of the feeding artery and draining vein or enhancement of the venous sac in the pulmonary arterial phase (before visualization of the normal pulmonary vein) (13). When reperfusion was diagnosed, repeat embolization was recommended. However, in patients with multiple PAVMs, embolization of all could not be accomplished in a single session, and PAVMs that had received embolization previously were evaluated by pulmonary angiography instead of time-resolved MR angiography during subsequent embolization sessions. Pulmonary angiography was performed only in such additional embolization cases. Additional embolization sessions were planned 2–5 months after the first session. When pulmonary angiography was performed from the main right or left pulmonary artery, a power injector was always used, and when it was performed from the feeding artery of the PAVM, contrast material was manually injected. Reperfusion was defined as simultaneous enhancement of the feeding artery and draining vein or the venous sac (8).
Image Acquisition and Reconstruction of Time-Resolved MR Angiography All studies were performed on a 1.5-tesla MR system (Achieva; Philips Healthcare, Best, The Netherlands) or 3.0-tesla system (Skyra; Siemens AG Medical Systems, Forchheim, Germany) using a five-element cardiac surface coil or an 18-element body coil, respectively. Timeresolved MR angiography was acquired with a threedimensional MR angiography T1-weighted fast-field echo sequence with the following parameters: for Achieva, repetition time/echo time ¼ 4.7/1.4 ms, flip angle ¼ 401, field of view ¼ 400 mm with 80% rectangular field of view, matrix ¼ 336 227, slice thickness ¼ 3 mm interpolated to 1.5 mm, and 25 slices acquired to cover a slab thickness of 37.5 mm; for Skyra, repetition time/echo time ¼ 2.1/0.9 ms, flip angle ¼ 101, field of view ¼ 430 mm, matrix 320 320, slice thickness ¼ 1.5 mm, and 40 slices acquired to cover a slab thickness of 60.0 mm. To reduce the number of inplane phase-encoding steps, parallel imaging and keyhole imaging techniques were applied with factors of 2.5 and 20%, respectively, for Achieva and factors of 3 and 10%, respectively, for Skyra, achieving temporal
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resolutions of 1.7 seconds and 1.0 second, respectively. Each slab was set to include the feeding artery, draining vein, and venous sac with portions of the aorta, main pulmonary artery, and left atrium to detect the temporal phase. There were 25 three-dimensional volumes acquired consecutively after a 5.0-second reference scan under breath-holding conditions. Data acquisition began simultaneously with a contrast medium injection (0.1 mmol/kg of gadolinium chelate [Magnevist; Bayer HealthCare Pharmaceuticals, Whippany, New Jersey]) at a flow rate of 2 mL/s, followed by a saline flush of 30 mL during breath-holding. All source images from each frame were reconstructed with a maximum intensity projection algorithm.
Statistical Analysis Differences in the location of PAVM, size of PAVM, and amount of coils in the two groups (nonreperfused and reperfused) were examined by χ2 test or t test. Reperfusion rates were calculated by the Kaplan-Meier method, and differences between the two groups, primary embolization versus repeat embolization and with versus without fibered coils, were examined by the logrank test. P o .05 was considered to indicate a significant difference. All statistical analyses were carried out using GraphPad Prism (GraphPad Software, Inc, La Jolla, California).
RESULTS Details of the PAVMs treated in the present study are summarized in Table 1. There were 23 PAVMs with a single feeding artery (simple type), and one PAVM had multiple feeding arteries (complex type). The results of each procedure included in this study are shown in Table E1 (available online at www.jvir.org), and details of the examinations conducted after these procedures are summarized in Figure 1. Only pulmonary angiography was performed for the 12 procedures on six PAVMs in one patient. Time-resolved MR angiography was initially Table 1 . Details of 24 PAVMs that Were the First Procedure at the Time of Entry in the Study Location RUL/RML/RLL/LUL/LLL
2/6/5/3/8
Size* Feeding artery (mm)
3.8 (1.4–5.2)
Venous sac (mm)
7 (2.8–26.6)
Type Simple/complex
23/1
Timing Primary/repeat
12/12
LLL ¼ left lower lobe, LUL ¼ left upper lobe, PAVM ¼ pulmonary arteriovenous malformation, RLL ¼ right lower lobe, RML ¼ right middle lobe, RUL ¼ right upper lobe. *Median (range).
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performed for the other 20 procedures on 18 PAVMs in 15 patients, and pulmonary angiography was performed for six procedures on six PAVMs in four patients. The remaining 14 procedures on 14 PAVMs in 12 patients were followed with time-resolved MR angiography only (one patient number and one PAVM number were duplicated in “time-resolved MR angiography and pulmonary angiography” and “time-resolved MR angiography only”; patient no. 16, PAVM no. 24 in Table E1 [available online at www.jvir.org]). In this study, seven of 24 PAVMs in seven patients were occluded, and the remaining 17 PAVMs in 11 patients were reperfused (two patients were duplicated in occluded PAVM and reperfused PAVM; patient no. 14 and patient no. 15 in Table E1, Figs 2a–e, 3a–d). We attempted embolization of two reperfused PAVMs (PAVM no. 2 and PAVM no. 3 in Table E1) in one patient but did not achieve complete cessation because of the lack of a margin for embolization; this indicated that the residual proximal feeder vessel length was insufficient, which may have caused the reflux of coils into normal pulmonary arterial branches when coil embolization was attempted (12). The other two reperfused PAVMs (PAVM no. 5 and PAVM no. 6 in Table E1) in the same patient also appeared to have no margin for embolization by pulmonary angiography and were observed. Paradoxical embolization has not yet occurred in this patient. Repeat embolization with hydrophilic coils was performed in four reperfused PAVMs (PAVM no. 1, PAVM no. 4, PAVM no. 18, and PAVM no. 22 in Table E1) in three patients, and repeat embolization with bare coils was performed in one reperfused PAVM (PAVM no. 12 in Table E1) in one patient; however, this patient moved to another hospital and could not be followed. The remaining eight reperfused PAVMs in seven patients were observed with timeresolved MR angiography because the patients did not agree to undergo repeat embolization. The reason for refusal was uncertainty to acquire complete occlusion with
Figure 1. Chart of follow-up examinations after procedures. PAG ¼ pulmonary angiography, TR-MRA ¼ time-resolved MR angiography. *PAG findings were in accordance with TR-MRA findings in all cases.
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the next procedure. Paradoxical embolization has not yet occurred. In all 16 patients, the follow-up period was defined as the interval between the first embolization procedure and last follow-up visit. The median follow-up period was 24 months (range, 1–39 mo). Two patients who did not have reperfusion were lost at 1 month (first follow-up) and 7 months (second follow-up), respectively, and the remaining 14 patients have had continuous follow-up evaluations. Of the 14 patients, 5 had less than a 24month follow-up period (median, 20 mo; range, 10–23 mo). The median periods of first, second, third, fourth, fifth, and sixth follow-up examinations were 2, 7, 14, 17, 19, and 21.5 months after coil embolization. In 25 of 32 procedures, reperfusion was detected at a median interval of 5 months (range, 1–18 mo), and there was no reperfusion in 7 procedures with a median interval of 20 months (range, 1–25 mo). Of the 25 reperfusions, 24 occurred because of recanalization through previously placed coils, and 1 was attributed to the development of an accessory pulmonary arterial feeder vessel, even though eight of 24 cases of recanalization through previously placed coils were evaluated with time-resolved MR angiography only. Bronchial artery hypertrophy was not detected in any patient, even in PAVM cases evaluated with time-resolved MR angiography only. In 24 PAVMs, the median size of the feeding artery was 3.8 mm (range, 1.4–5.2 mm), and the median size of the venous sac was 7 mm (range, 2.8–26.6 mm). The median number of coils was 10 (range, 3–57), and the median length of all coils used was 82 cm (range, 20– 1,455 cm). Details regarding the PAVM location and size and coils used in the nonreperfused and reperfused groups based on PAVMs are summarized in Table 2. No significant differences were observed between the two groups in any of these parameters. The reperfusion rates of primary embolization and repeat embolization were compared. In the 24 PAVMs, the 3month, 6-month, 12-month, and 24-month reperfusion rates were 8%, 27%, 36%, and 49%, respectively, for the 12 untreated PAVMs (primary embolization) and 50%, 50%, 92%, and 100%, respectively for the 12 reperfused PAVMs (repeat embolization) (P ¼ .0062) (Fig 4). In all 32 procedures, the 3-month, 6-month, 12-month, and 24month reperfusion rates were 8%, 27%, 36%, and 49%, respectively, for the 12 primary embolization procedures and 45%, 65%, 95%, and 100%, respectively, for the 20 repeat embolization procedures (P ¼ .0011). The reperfusion rates after the second embolization versus the third, fourth, or fifth embolization were as follows: the 3-month, 6-month, 12-month, and 24-month reperfusion rates were 50%, 50%, 93%, and 100%, respectively, for the 14 second embolization procedures and 33%, 100%, 100%, and 100%, respectively, for the six third, fourth, or fifth embolization procedures (P ¼ .22). The reperfusion rates of embolization evaluated with or without fibered coils were compared. Coil embolization
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Figure 2. A 53-year-old woman presented with reperfused PAVM of the left lower lobe. Reperfusion was suspected on a CT scan, and pulmonary angiography was performed 65 months after primary embolization. (a) Angiography from the feeding artery (arrowhead) at primary embolization shows PAVM in the left lower lobe (arrow). (b) Angiography from inside of the original coils of the feeding artery (arrowhead) performed 65 months after primary embolization shows reperfusion (arrow). A second embolization was performed. (c) Angiography from the feeding artery performed after 2 months shows reperfusion (arrow). A third embolization was performed. (d) Angiography from the left pulmonary artery performed after 4 months shows reperfusion (arrow). A fourth embolization was performed. (e) Angiography from the left pulmonary artery after 5 months shows reperfusion (arrow). Because there was no margin to place coils, embolization could not be performed.
was performed with bare coils only in 12 PAVMs, with fibered coils only in one PAVM, and with both bare and fibered coils in 11 PAVMs. Fibered coils were used in 12 of the 24 PAVMs. The 3-month, 6-month, 12-month, and 24-month reperfusion rates were 50%, 58%, 83%, and 92%, respectively, in 12 PAVMs with embolization without fibered coils and 8%, 18%, 48%, and 60%, respectively, in 12 PAVMs with embolization with fibered coils (P ¼ .063) (Fig 5).
DISCUSSION Follow-up examinations after successful coil embolization are important for detecting reperfusion, and DSA is the most sensitive modality used to examine blood flow through lesions because it detects simultaneous enhancements in the feeding artery and draining vein
in reperfused PAVMs (8). In occluded PAVMs, as in normal pulmonary vessels, enhancements in the vein have been shown to occur within a few seconds of visualizing the artery (8). However, because DSA is an invasive follow-up examination, CT has been routinely performed. The reperfusion rates evaluated by CT were previously reported to be up to 19% (9–12). However, the CT criteria reported in the literature included the complete, or at least a 70%, reduction in a draining vein and venous sac or their contrast enhancements; CT is considered to provide only an indirect finding (1,8– 12,14). Difficulties have been associated with evaluating CT images because of image deterioration secondary to metal artifacts generated by the coils (8,9,15). Time-resolved MR angiography has become a valuable option as an alternative to DSA for screening after coil embolization because of its high sensitivity in detecting flow and the absence of ionizing radiation,
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Figure 3. A 72-year-old woman presented with untreated PAVM of the left lower lobe. (a) Angiography of the left pulmonary artery shows PAVM in the left lower lobe (arrow). (b) Angiography after coil embolization shows complete occlusion of PAVM. (c) Timeresolved MR angiography performed 1 month after coil embolization shows slight blood flow from the PAVM (arrow), leading to a diagnosis of reperfusion. (d) Angiography performed 2 months after coil embolization shows slight reperfusion (arrow). Repeat embolization was performed.
and it offers a noninvasive examination with high resolution (16). Platinum coils, which have relatively low paramagnetic characteristics, are known to produce very few artifacts in MR imaging (13,17,18), and only platinum coils were used in this study. Kawai et al (13) reported the usefulness of time-resolved MR angiography over CT in diagnosing the reperfusion of PAVM after coil embolization. They demonstrated that timeresolved MR angiography displayed high diagnostic
specificity, positive predictive values, and sensitivity, and these values were in marked contrast to values obtained using CT. In the present study, reperfusion was evaluated using time-resolved MR angiography or pulmonary angiography, both of which can depict blood flow by reperfusion, and reperfusion rates were markedly higher than rates reported in the literature. Recognizing high reperfusion rates and how to decrease them is of clinical importance.
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Table 2 . Details of PAVM Location and Size and Coils in Nonreperfused and Reperfused Groups Based on PAVMs Nonreperfused (n ¼ 7)
Reperfused (n ¼ 17)
P
Location 0/1/1/2/3
2/5/4/1/5
.43
Size of PAVM* Feeding artery (mm)
RUL/RML/RLL/LUL/LLL
3 (2–4)
3.8 (1.4–5.2)
.12
Venous sac (mm)
4.6 (2.8–15.5)
7 (3.9–26.6)
.50
12 (3–23)
10 (4–57)
.98
129 (28–182)
72 (20–1,455)
.72
Coils* Number of coils Total length (cm)
LLL ¼ left lower lobe, LUL ¼ left upper lobe, PAVM ¼ pulmonary arteriovenous malformation, RLL ¼ right lower lobe, RML ¼ right middle lobe, RUL ¼ right upper lobe. *Median (range).
Figure 4. Reperfusion curves in the two groups undergoing primary embolization and repeat embolization. The reperfusion rate was significantly higher in the repeat embolization group (P ¼ .0062).
Embolization of the feeding artery and the venous sac was previously shown to prevent reperfusion (1,19), and our primary embolization was performed according to this method in the present study. However, the reperfusion rates of primary embolization were higher; the 3month, 6-month, 12-month, and 24-month reperfusion rates for the 12 primary embolization procedures were 8%, 27%, 36%, and 49%, respectively. Reperfusion rates were markedly worse with repeat embolization; the 3month, 6-month, 12-month, and 24-month reperfusion rates were 50%, 50%, 92%, and 100%, respectively. The sensitivity of time-resolved MR angiography appears to be very high, allowing even slightly reperfused flow to be detected. We speculated that the risk of paradoxical embolization may be decreased when the amount of blood flow in the right-to-left shunt decreases. However, the risk may not be zero because symptomatic paradoxical embolization was reported in patients with only sub-3-mm feeding arteries (20,21), even though the indication for PAVM embolization used to be a feeding artery Z 3 mm (6). Shovlin et al (22) stated that the size of PAVM did not predict the risk of brain abscesses and ischemic stroke. However, Lee et al (23) reported that contrast echocardiography was positive in 79% of patients after successful embolization, and they suspected that these patients may have small PAVMs
Figure 5. Reperfusion curves in the two groups undergoing embolization with and without fibered coils. No significant differences were observed in reperfusion rates between the two groups (P ¼ .063).
that were undetectable by pulmonary angiography. These authors considered whether such very small PAVMs were clinically relevant. It is uncertain at the present time whether slight reperfusion detected with time-resolved MR angiography is clinically relevant, and it is difficult to determine the amount of reperfusion flow that is considered clinically problematic. This issue needs to be examined in more detail in a larger study, in which how much flow of the reperfusion is relevant should be investigated by carefully observing patients with reperfusion who refuse repeat embolization. Lee et al (9) reported that interim ischemic strokes occurred in two of eight patients with persistent PAVMs. Repeat embolization for reperfusion has been reported previously (9,12,24), and we consider retreatment to be necessary for reperfusion. Repeat embolization is recommended in our hospital, and patients who refused this treatment were observed. However, reperfusion rates with repeat embolization were worse than rates with primary embolization in the present study. Although the complete cessation of reperfusion is obtained at the end of the repeat embolization procedure, more coils may need to be placed into the feeding artery. Fibered coils were previously shown to produce thrombosis more effectively than bare coils (25), and reperfusion rates with or without fibered coils were assessed. Although no significant difference was observed, the P value was
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.063; embolization without fibered coils may cause reperfusion more than embolization with fibered coils. The most common mechanism underlying reperfusion is recanalization through previously placed coils (12,15), and this is generally considered to occur because of the elongation of coils or an insufficient number of coils, both of which may cause a failure in the formation of a thrombus (26). Tight embolization is important for preventing coil elongation. Although we performed coil embolization as tightly as possible in all cases in the present study, our reperfusion rate was still high. We assumed that coil elongation could not be completely prevented when coil embolization was performed. An AMPLATZER vascular plug (St Jude Medical, Inc, St Paul, Minnesota) was reported as a useful material for PAVM with low recanalization rates (up to 7%) (14,27). The use of a hydrophilic coil in embolization for cerebral aneurysm has been shown to prevent recanalization (28,29). Hydrophilic coils are made of platinum helical coils coated with a layer of hydrophilic acrylic polymer (hydrogel), which, on contact with blood, causes the disentanglement of polymer chains and expansion (30). It contributes to a higher packing density and lower thromboembolic rate (31). In Japan, health insurance coverage of AMPLATZER vascular plugs and hydrophilic coils is only more recent; the usefulness of these embolic materials for PAVM needs to be examined with time-resolved MR angiography in future studies. The reperfusion of PAVM after coil embolization may have been due not only to technical issues but also to the characteristics of the pulmonary artery. The pulmonary and systemic circulatory systems transport an equal amount of blood; however, the pulmonary circulation operates at markedly lower pressures than the systemic circulation. Pulmonary pressure is lower because resistance is lower, and the pulmonary vasculature is more compliant, and this compliance has been attributed to arterial wall elasticity and vessel size (32). We speculated that this high compliance made the pulmonary artery distend after coil embolization, leading to coil elongation. Our study has several limitations. The small sample size and retrospective design were key limitations. The time-resolved MR angiography equipment varied among patients, as did spatial and temporal resolutions. Although the 3.0-tesla MR system was superior to the 1.5-tesla MR system in these points, we considered it possible to obtain sufficient resolution to diagnose reperfusion even with 1.5-tesla MR. It was also difficult to measure the technical outcomes of coil embolization, even though complete cessation was confirmed by DSA after embolization. However, this measurement may be possible if the packing ratio of coils is calculated, similar to the embolization of an aneurysm (33), and coil placement is continued until a defined ratio even after complete cessation is confirmed. In addition, 20 procedures were evaluated with time-resolved MR
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angiography. Pulmonary angiography was performed after time-resolved MR angiography in six of these procedures, and consistency among the results obtained was confirmed. However, pulmonary angiography was not performed after the other 14 time-resolved MR angiography scans. Time-resolved MR angiography findings in 14 cases were not confirmed by pulmonary angiography. In previous studies, 0.035-inch coils were used, and reperfusion rates were lower than rates in the present study (10,15,34). However, microcoils were used in all procedures in this study, which may have contributed to the higher reperfusion rates. Future studies are warranted to clarify this issue. Another limitation is that the follow-up period was relatively shorter than that in the literature. However, our reperfusion rates were high even with the short follow-up period, which was an important finding. In conclusion, reperfusion rates after coil embolization for PAVM were higher than rates previously reported when an evaluation of reperfusion with time-resolved MR angiography or pulmonary angiography was performed. Further studies are needed to investigate longterm outcomes with a larger study cohort.
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24. Woodward CS, Pyeritz RE, Chittams JL, et al. Treated pulmonary arteriovenous malformations: patterns of persistence and associated retreatment success. Radiology 2013; 269:919–926. 25. Graves VB, Partington CR, Rüfenacht DA, et al. Treatment of carotid artery aneurysms with platinum coils: an experimental study in dogs. AJNR Am J Neuroradiol 1990; 11:249–252. 26. Sagara K, Miyazono N, Inoue H, et al. Recanalization after coil embolotherapy of pulmonary arteriovenous malformations: study of long-term outcome and mechanism for recanalization. AJR Am J Roentgenol 1998; 170:727–730. 27. Tapping CR, Ettles DF, Robinson GJ. Long-term follow-up of treatment of pulmonary arteriovenous malformations with AMPLATZER Vascular Plug and AMPLATZER Vascular Plug II devices. J Vasc Interv Radiol 2011; 22:1740–1746. 28. White PM, Lewis SC, Gholkar A, et al. Hydrogel-coated coils versus bare platinum coils for the endovascular treatment of intracranial aneurysms (HELPS): a randomised controlled trial. Lancet 2011; 377:1655–1662. 29. Gunnarsson T, Tong FC, Klurfan P, et al. Angiographic and clinical outcomes in 200 consecutive patients with cerebral aneurysm treated with hydrogel-coated coils. AJNR Am J Neuroradiol 2009; 30:1657–1664. 30. Cantón G, Levy DI, Lasheras JC. Changes in the intraaneurysmal pressure due to HydroCoil embolization. AJNR Am J Neuroradiol 2005; 26:904–907. 31. White PM, Lewis SC, Nahser H, et al. HydroCoil Endovascular Aneurysm Occlusion and Packing Study (HELPS trial): procedural safety and operatorassessed efficacy results. AJNR Am J Neuroradiol 2008; 29:217–223. 32. Saouti N, Westerhof N, Postmus PE, Vonk-Noordegraaf A. The arterial load in pulmonary hypertension. Eur Respir Rev 2010; 19:197–203. 33. Yasumoto T, Osuga K, Yamamoto H, et al. Longterm outcomes of coil packing for visceral aneurysms: correlation between packing density and incidence of coil compaction or recanalization. J Vasc Interv Radiol 2013; 24:1798–1807. 34. Andersen PE, Kjeldsen AD. Clinical and radiological long-term follow-up after embolization of pulmonary arteriovenous malformations. Cardiovasc Intervent Radiol 2006; 29:70–74.
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Table E1 . Results of Each Procedure Included in Study Results of Each Procedure Patient No.
Second
Third
Fourth
Fifth
1
○
○
○
○
2 3
○ ○
○ ○
○
4 5 6 2 3 4
1
PAVM No.
First
Final Outcome
Strategy/Status at Reperfusion
Reperfused
Embolization with hydrophilic coils
Reperfused Reperfused
Complete cessation not obtained Complete cessation not obtained
○
Reperfused
Embolization with hydrophilic coils
○ ○
Reperfused Reperfused
No margin for embolization No margin for embolization
7
□
Reperfused
Observation
8 9
□ □
Reperfused Reperfused
Observation Observation
5
10
□
Reperfused
Observation
6 7
11 12
□ □○
Reperfused Reperfused
Observation Follow-up at another hospital
8
13
■
Occluded
—
9 10
14 15
■ ■
Occluded Occluded
— —
11
16
■
Occluded
—
12 13
17 18
■ □○
Occluded Reperfused
— Embolization with hydrophilic coils
14
19
■
Occluded
—
15
20 21
□ ■●
Reperfused Occluded
Observation —
22
□○
Reperfused
Embolization with hydrophilic coils
23 24
□ □○
Reperfused Reperfused
Observation Observation
16
□○
□
□ ¼ reperfusion diagnosed with time-resolved MR angiography performed, ■ ¼ no reperfusion diagnosed with time-resolved MR angiography performed, ○ ¼ reperfusion diagnosed with pulmonary angiography, ● ¼ no reperfusion diagnosed with pulmonary angiography, PAVM = pulmonary arteriovenous malformation.
