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Pseudo-arterio-arterial anastomoses in twin–twin transfusion syndrome
Placenta (2004), 25, 742–747 doi:10.1016/j.placenta.2004.02.010
Pseudo-arterio-arterial Anastomoses in Twin–Twin Transfusion Syndrome M. J. O. Taylor*, D. Talbert and N. M. Fisk Centre for Fetal Care, Queen Charlotte’s and Chelsea Hospital and Institute of Reproductive and Developmental Biology, Imperial College, London, UK Paper accepted 2 February 2004
Objective: It has recently been claimed that fetoscopic recognition of a haemodynamic equator within an arterio-arterial anastomosis (AAA) suggests minimal net intertwin flow. This was based on blood from one fetus being dark and from the other bright red, the boundary between them reciprocating with the fetal heart beats. However, bright red indicates that the blood had passed through a cotyledon and been freshly oxygenated, which should be impossible in an AAA. We applied a computer model of chorionic vessels to determine a configuration that reproduced this phenomenon. Methods: A previously published TTTS model was extended to provide placental detail in a segment containing four cotyledons of each placenta supplied by three generations of placental arteries and veins. Results: Reciprocating flow is not unique to AAAs. It also occurs in the chorionic arteries of any cotyledon deprived of its venous outflow, in a similar manner to that in which reverse end-diastolic flow occurs in umbilical arteries when whole placental resistance is high. If venous return from the common chorionic vein in the recipient (draining the venous end of an AVA) is blocked as might happen after laser, there can be bidirectional flow from one umbilical artery insertion, through two cotyledons to the other insertion. We define this phenomenon as a pseudo-AAA (PAAA). The inclusion of two cotyledons in this path means that its resistance cannot match the low flow resistance of a true AAA, and transmission of the contralateral pulsatile pattern is absorbed in the cotyledons. Thus, PAAA Doppler patterns differ from true AAA patterns in that two sets of systolic peaks, one forward and one reverse, can be discerned in true AAAs but only one in PAAAs. Conclusions: We demonstrate how venous occlusion of an arterio-venous anastomosis may produce a pseudo-AAA colour equator at endoscopy. However, visual observation of reciprocating flow is not sufficient to define a vessel as a true AAA which instead requires ultrasonical identification of two systolic patterns. Placenta (2004), 25, 742–747 Ó 2004 Elsevier Ltd. All rights reserved.
INTRODUCTION There has been considerable controversy about the protective effect of arterio-arterial anastomoses (AAAs) in monochorionic twin pregnancies. AAAs have been found much less frequently in pregnancies complicated by twin–twin transfusion syndrome (TTTS) than in those that are not, and there are theoretical reasons why AAAs might protect against TTTS [1–6]. Furthermore, TTTS cases with an AAA present have a better perinatal outcome than those without an AAA [7]. While there is general agreement that AAAs present a significant hazard if one twin dies in utero, their therapeutic effect in restraining the excessive pressure deviations that occur * Corresponding author. Department of Obstetrics and Gynaecology, Royal Devon and Exeter Hospital (Heavitree), Gladstone Road, Exeter EX1 2ED, UK. Tel.: +44-1392-405054; fax: +44-1392405061. E-mail address: [email protected] (M.J.O. Taylor). 0143–4004/$–see front matter
in the presence of asymmetric arterio-venous anastomoses (AVAs), thus preventing or minimising chronic transfusional imbalance, has been disputed [8]. AAAs can be recognised functionally by their characteristic bidirectional periodic interference pattern on colour Doppler [1]. Their presence can also be inferred anatomically at fetoscopy as a single continuous non-terminating chorionic artery running between the two umbilical cord insertions. It has recently been claimed that AAAs can be recognised functionally at fetoscopy by their reciprocating flow and that their displacement was too small (!1 cm) to mediate any net intertwin transfusion [8]. In their pictorially elegant report, Bermudez et al. suggest the term haemodynamic equator (HE) to describe the interface between blood from each fetus. In their Figure 1 they show evidence of reciprocating movement of this HE, characteristic of AAA flow, in endoscopic images of an AAA within the donor’s territory. The demarcation of the HE is clearly seen because blood from one twin is dark red, characteristic of umbilical artery blood, and that from the other is described as Ó 2004 Elsevier Ltd. All rights reserved.
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Figure 1. Schematic of the endoscopic Figure 1 of Bermudez et al. [8]. B1 corresponds to B in that figure. Haemodynamic equator (HE) is the interface between bright red blood from the recipient (R) and dark blood from the donor. It reciprocates over a distance of approximately 8 mm between the positions shown in the left and right panels. The interface is transverse, presumably because when it reaches branch B2 (right panel), the end of the red column of blood is swept away down the branch B2.
‘‘bright red’’. Figure 1 shows the essential features of their illustration. They identify the interface between blood from the two fetuses by abrupt change of colour, bright red from the recipient and dark from the donor. It is generally assumed that the pressure in an AAA lies somewhere between the pressures at each twin’s umbilical artery insertion. It is thus difficult to understand how bright red blood that must have passed through a placental cotyledon to become bright red could have sufficient pressure to come to be in an AAA. In the fetus, arterial blood is normally 60% saturated; although saturations may differ in two twins affected by severe TTTS, both would inevitably have a deeper colour than fetal venous blood typically at 80% saturation. The clinical data for this case provided sufficient detail to enable a computer model to be adjusted to match. We extended the placental detail of our previous model and ‘‘lasered’’ various vessels within it until the phenomenon was reproduced. METHODS Modelling technique The model used was based on our previous report [9] which details the methodology and relationships between hydrostatic and osmotic pressures and their relation in turn to various possible anastomotic configurations. For this study, each placenta was effectively divided into major and minor sectors, the major retaining much of the original code and the minor a more detailed version shown in Figure 2. Three generations of chorionic arteries feed sets of four cotyledons of each placenta, which are drained by three generations of chorionic veins. An AVA can be introduced between these sectors by causing a cotyledon from twin A to drain into the same third generation chorionic vein in placenta B as one of its own cotyledons. ‘‘Water columns’’ are connected to various significant points of the model to provide visualisation of pressures as they change when adjustments are
made. Provision was made for the operator to ‘‘laser’’ (occlude) various vessels to block flow through them. Experimental design The initial stage was to investigate any combination of connections that could induce blood that had passed through a cotyledon to appear in an AAA. This was unsuccessful as no configuration was found in which villus pressure could be raised to equal that in an AAA in order to bring oxygenated blood up into an AAA. The AAA was then removed and an interconnection pattern derived from the staging data installed. Bermudez et al. give their own proposed staging definitions on which the patient rated stage III TTTS. According to this definition, donor urine output is usually absent, or reduced so much that the bladder is not visible, and umbilical artery Doppler showed absence of end-diastolic flow. Cessation of urine production thus indicates that the donor’s mean arterial pressures were lower than normal. Conversely, in the recipient, the atrial natiuretic peptide mediated polyuria and hence polyhydramnios indicated raised intracardiac pressures. These features are associated with AVAs in only one direction and no AAA to allow return flow. In our model, we therefore introduced a single AVA between the twins which is the simplest connection preventing urine production in the donor. Figure 2a represents the hypothesised condition of this patient before treatment. RESULTS ‘‘Lasering’’ the interconnecting vessel (blue dot, Figure 2b) allowed all pressures to return to normal, except those associated with the donor cotyledon (A4) whose venous return vessel previously formed the AVA link. The pressure and flow changes are illustrated in Figure 3. Before laser (Figures 2a, 3a), pressure in the chorionic artery driving blood towards the
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cotyledon (Pchora2A2) in Figure 3a is always higher than that at entry to the cotyledon (PcotaA4) and so flow (dQchora3A4), although pulsatile, is always into cotyledon A4. When the communicating vessel was occluded (Figure 2b), blood could no longer escape from A4, and its intravillous pressure, and hence stem vein pressure (PcotvA4), rose to its arterial mean pressure (Figure 3b, magenta). The Pchora2A2 and PcotaA4 pressure traces then gradually overlapped (Figure 3b) driving blood towards the cotyledon at systole and producing back flow in diastole. (This is a microversion of reverse enddiastolic flow in complete placentas occurring when placental resistance is pathologically increased.) In the final stable condition (Figure 3c), forward and reverse flows have become equal as the mean flow has to be zero. Although this reproduced the reciprocating flow seen endoscopically, it did not explain the changes in position along the artery reported to occur from moment to moment. Recently, a case was reported in which clotting occurred in a placental vein draining several AVAs, which had produced sudden onset of TTTS [10]. This drew attention to the possible hazards of loss of venous return in an AVA. The tertiary vein shared by cotyledon A4 in the donor and cotyledon B1 in the recipient (Figure 2c) was ‘‘lasered’’ instead of the connecting vessel. Because the blood in cotyledons A4 and B1 then had no return path, their internal (villous) pressures (Pcotv4, Pcotv1, Figure 2c) rose to the mean pressure at the bifurcation of the second generation chorionic arteries supplying cotyledons 3 and 4 of the donor’s placenta and cotyledons 1 and 2 of the recipient’s placenta. The mean pressure at the bifurcation then rose, eventually falling and rising above that in the donor’s cotyledons 3 and 4, each cardiac cycle, producing a reciprocating flow superficially similar to that in genuine AAAs (Figure 3d). The high compliance of the cotyledons absorbs the pulsatile aspects of the pressures from the contralateral twin, so that each twin ‘‘sees’’ a cotyledon whose venous pressure is similar to its own arterial pressure, and reciprocating arterial flow developed as before. But now cotyledons A4 and B1 are connected in series between the two chorionic artery networks and any small change in cardiac output in either twin will produce a change in umbilical artery pressure which will in turn produce a net displacement of blood in the communicating vessel. This may displace the HE in the chorionic artery of the donor (in the donor’s territory) as described by Bermudez et al. If this unidirectional flow is from recipient to donor, the
745
HE can be carried back to the first branch and the artery may appear permanently bright red. If in the opposite direction, the HE disappears into the cotyledon, and the artery will appear normal dark red in colour. If reciprocation carries the HE up to the branch and back again, the interface between blood from the two fetuses will be sharp and approximately transverse as they describe. DISCUSSION Using a computer model, it has been possible to reproduce the critical features of the reported apparent AAA equator at fetoscopy, without introducing a true AAA, namely: (1) a reciprocating boundary between dark red blood from one fetus and bright red blood from the other fetus, (2) occurrence in an artery within the donor’s territory, and (3) a slow displacement of this boundary towards or away from a branch artery. The key to the phenomenon is loss of a local venous return path. This might arise naturally [10] or as a result of intentional laser ablation of an AVA. But since the flow along this pseudoanastomosis necessarily has to pass through two cotyledons, it will be very much smaller than that mediating the protective haemodynamic effects of a true low resistance AAA. Hence, we term this high resistance path a pseudo-AAA (PAAA). Bermudez et al.’s contention that AAAs do not protect against haemodynamic imbalance in MC twins might be due to their misidentification of such chorionic arteries as AAAs on the basis of reciprocating flow. Endoscopically, if reciprocating flow brings bright red blood into the artery under investigation, the colour indicates that it obviously cannot be a genuine AAA. Ultrasonically, the two vessels can easily be distinguished by fundamental differences in Doppler waveforms. This results from the smoothing out of arterial flow pulsatility as blood passes through the two cotyledons forming the link in the PAAA. Thus, in a PAAA only the ipsilateral systolic peak will be seen, whereas in a genuine AAA, the systoles of both fetuses, one upwards and one downwards, will be seen, with a cyclic fluctuating pattern at the difference in frequency of the two fetal hearts. We and others (Hecher, personal communication) have not seen this HE/pseudo-AAA pattern at endoscopy. This may relate to differences in laser technique, as this pattern will not arise when both the arterial and the venous ends of an AVA are lasered and completely ablated.
Figure 2. The diagram represents minor segments of the placentas of the ‘‘donor’’ (‘‘A’’ left) and the ‘‘recipient’’ (‘‘B’’ right). Some of the more significant pressures are represented as if water columns were connected to them, to permit visualisation. The height of the columns is adjusted by the model as it runs. The starting point in (a) shows the model set up to represent part of a monochorial placenta in TTTS. The connecting AVA runs from the third generation chorionic artery feeding the fourth cotyledon from the left in the donor placenta (Pcota4), through that cotyledon to its stem vein (Pcotv4), across to the stem vein of cotyledon 1 of the recipient (Pcotv1) and down through the third generation vein in the recipient’s placenta which also drains the recipient cotyledon 1 to the second generation vein Pchorv2. Pressures in the donor have fallen and pressures in the recipient have risen until there is little average flow along the AVA. In (b) the connecting vessel has been lasered (blue spot). Pressures in both fetuses have started to normalise generally, except in the fourth cotyledon of the donor whose drainage path has been blocked. It fills to the ex-donor’s mean chorionic artery pressure at Pchora2, and as the instantaneous pressure Pchora2 rises and falls past the mean pressure held at Pcota4, flow reverses in the third generation artery Pcota4 to Pchora2. In (c) the third generation vein that was providing the common drainage for the connected cotyledons has been lasered. Here, pressure in both cotyledons rises to arterial values and there is in fact a path from the umbilical artery of one fetus, through the two cotyledons, and out to the umbilical artery of the other fetus.
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(a)
(b)
(c)
(d) Figure 3. Pressures corresponding to conditions in Figure 2a are shown in (a). Flow in the third generation chorionic artery feeding cotyledon A4 (dQchora3A4) shown before lasering in (a), immediately following lasering (b), and after flow stabilisation in (c). The pressure driving blood into it (from the second generation chorionic artery (Pchora2A2)) is shown above in the red trace, and the pressure it produces at the cotyledon’s stem artery (PcotaA4) in magenta. Cotyledons A4 and B1 are modelled as being close and so pressures at the cotyledon stem veins, PcotvA4 and PcotvB1, are virtually the same before the AVA is occluded. Before the AVA is occluded, Pchora2A2 is always greater than PcotaA4 and so flow into cotyledon A4 is unidirectional throughout the cardiac cycle. When the AVA is occluded, (b) blood has no path to leave the donor’s cotyledon 4 and accumulates, revealed as a steadily rising pressure in its stem vein (PcotvA4), whereas the loss of this supplementing flow causes a drop in cotyledon B1 stem vein pressure (PcotvB1). As blood accumulates in cotyledon A4, the resulting back pressure (PcotaA4) rises above that in Pchora2A2 for part of the cardiac cycle, causing the flow (dQchora3A4) to reverse whenever the two pressures cross. It then becomes increasingly bi-phasic until it settles to a balanced pattern (c) whose outline follows that of the driving pressure in the donor’s chorionic artery. A true AAA waveform is shown in (d) for comparison. At different parts of the ‘‘beat’’ cycle, the steep fronted systolic peaks of each umbilical artery pressure appear as mirror images of each other. In the PAAA flow pattern, there is only one set of steep fronted systolic peaks (c).
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ACKNOWLEDGEMENTS The authors thank the Richard and Jack Wiseman Trust for financial support, and Sport Aiding Research into Kids (SPARKS) and Children Nationwide Medical Research Fund for equipment support.
REFERENCES [1] Taylor MJ, Denbow ML, Tanawattanacharoen S, Gannon C, Cox PM, Fisk NM. Doppler detection of arterio-arterial anastomoses in monochorionic twins: feasibility and clinical application. Hum Reprod 2000; 15(7):1632–6. [2] Bajoria R, Wigglesworth J, Fisk NM. Angioarchitecture of monochorionic placentas in relation to the twin–twin transfusion syndrome. Am J Obstet Gynecol 1995;172(3):856–63. [3] Denbow ML, Cox P, Talbert D, Fisk NM. Colour Doppler energy insonation of placental vasculature in monochorionic twins: absent arterio-arterial anastomoses in association with twin-to-twin transfusion syndrome. Br J Obstet Gynaecol 1998;105(7):760–5. [4] Denbow ML, Cox P, Taylor M, Hammal DM, Fisk NM. Placental angioarchitecture in monochorionic twin pregnancies: relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome. Am J Obstet Gynecol 2000;182(2):417–26. [5] Umur A, van Gemert MJ, Nikkels PG, Ross MG. Monochorionic twins and twin–twin transfusion syndrome: the protective role of arterioarterial anastomoses. Placenta 2002;23(2–3):201–9.
[6] Tan T, Denbow ML, Cox PM, Talbert P, Fisk NM. Occlusion of arterio-arterial anastomosis manifesting as acute twin–twin transfusion syndrome. Placenta 2004;25:238–42. [7] Taylor MJO, Denbow ML, Duncan KR, Overton TG, Fisk NM. Antenatal factors at diagnosis predictive of survival in severe twin–twin transfusion syndrome. Am J Obstet Gynecol 2000;183: 1023–8. [8] Bermudez C, Becerra CH, Bornick PW, Allen MH, Arroyo J, Quintero RA. Placental types and twin–twin transfusion syndrome. Am J Obstet Gynecol 2002;187(2):489–94. [9] Talbert DG, Bajoria R, Sepulveda W, Bower S, Fisk NM. Hydrostatic and osmotic pressure gradients produce manifestations of fetofetal transfusion syndrome in a computerized model of monochorial twin pregnancy. Am J Obstet Gynecol 1996;174(2): 598–608. [10] Nikkels PG, van Gemert MJ, Sollie-Szarynska KM, Molendijk H, Timmer B, Machin GA. Rapid onset of severe twin–twin transfusion syndrome caused by placental venous thrombosis. Pediatr Dev Pathol 2002;5(3):310–4.
Pseudo-arterio-arterial Anastomoses in Twin–Twin Transfusion Syndrome M. J. O. Taylor*, D. Talbert and N. M. Fisk Centre for Fetal Care, Queen Charlotte’s and Chelsea Hospital and Institute of Reproductive and Developmental Biology, Imperial College, London, UK Paper accepted 2 February 2004
Objective: It has recently been claimed that fetoscopic recognition of a haemodynamic equator within an arterio-arterial anastomosis (AAA) suggests minimal net intertwin flow. This was based on blood from one fetus being dark and from the other bright red, the boundary between them reciprocating with the fetal heart beats. However, bright red indicates that the blood had passed through a cotyledon and been freshly oxygenated, which should be impossible in an AAA. We applied a computer model of chorionic vessels to determine a configuration that reproduced this phenomenon. Methods: A previously published TTTS model was extended to provide placental detail in a segment containing four cotyledons of each placenta supplied by three generations of placental arteries and veins. Results: Reciprocating flow is not unique to AAAs. It also occurs in the chorionic arteries of any cotyledon deprived of its venous outflow, in a similar manner to that in which reverse end-diastolic flow occurs in umbilical arteries when whole placental resistance is high. If venous return from the common chorionic vein in the recipient (draining the venous end of an AVA) is blocked as might happen after laser, there can be bidirectional flow from one umbilical artery insertion, through two cotyledons to the other insertion. We define this phenomenon as a pseudo-AAA (PAAA). The inclusion of two cotyledons in this path means that its resistance cannot match the low flow resistance of a true AAA, and transmission of the contralateral pulsatile pattern is absorbed in the cotyledons. Thus, PAAA Doppler patterns differ from true AAA patterns in that two sets of systolic peaks, one forward and one reverse, can be discerned in true AAAs but only one in PAAAs. Conclusions: We demonstrate how venous occlusion of an arterio-venous anastomosis may produce a pseudo-AAA colour equator at endoscopy. However, visual observation of reciprocating flow is not sufficient to define a vessel as a true AAA which instead requires ultrasonical identification of two systolic patterns. Placenta (2004), 25, 742–747 Ó 2004 Elsevier Ltd. All rights reserved.
INTRODUCTION There has been considerable controversy about the protective effect of arterio-arterial anastomoses (AAAs) in monochorionic twin pregnancies. AAAs have been found much less frequently in pregnancies complicated by twin–twin transfusion syndrome (TTTS) than in those that are not, and there are theoretical reasons why AAAs might protect against TTTS [1–6]. Furthermore, TTTS cases with an AAA present have a better perinatal outcome than those without an AAA [7]. While there is general agreement that AAAs present a significant hazard if one twin dies in utero, their therapeutic effect in restraining the excessive pressure deviations that occur * Corresponding author. Department of Obstetrics and Gynaecology, Royal Devon and Exeter Hospital (Heavitree), Gladstone Road, Exeter EX1 2ED, UK. Tel.: +44-1392-405054; fax: +44-1392405061. E-mail address: [email protected] (M.J.O. Taylor). 0143–4004/$–see front matter
in the presence of asymmetric arterio-venous anastomoses (AVAs), thus preventing or minimising chronic transfusional imbalance, has been disputed [8]. AAAs can be recognised functionally by their characteristic bidirectional periodic interference pattern on colour Doppler [1]. Their presence can also be inferred anatomically at fetoscopy as a single continuous non-terminating chorionic artery running between the two umbilical cord insertions. It has recently been claimed that AAAs can be recognised functionally at fetoscopy by their reciprocating flow and that their displacement was too small (!1 cm) to mediate any net intertwin transfusion [8]. In their pictorially elegant report, Bermudez et al. suggest the term haemodynamic equator (HE) to describe the interface between blood from each fetus. In their Figure 1 they show evidence of reciprocating movement of this HE, characteristic of AAA flow, in endoscopic images of an AAA within the donor’s territory. The demarcation of the HE is clearly seen because blood from one twin is dark red, characteristic of umbilical artery blood, and that from the other is described as Ó 2004 Elsevier Ltd. All rights reserved.
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Figure 1. Schematic of the endoscopic Figure 1 of Bermudez et al. [8]. B1 corresponds to B in that figure. Haemodynamic equator (HE) is the interface between bright red blood from the recipient (R) and dark blood from the donor. It reciprocates over a distance of approximately 8 mm between the positions shown in the left and right panels. The interface is transverse, presumably because when it reaches branch B2 (right panel), the end of the red column of blood is swept away down the branch B2.
‘‘bright red’’. Figure 1 shows the essential features of their illustration. They identify the interface between blood from the two fetuses by abrupt change of colour, bright red from the recipient and dark from the donor. It is generally assumed that the pressure in an AAA lies somewhere between the pressures at each twin’s umbilical artery insertion. It is thus difficult to understand how bright red blood that must have passed through a placental cotyledon to become bright red could have sufficient pressure to come to be in an AAA. In the fetus, arterial blood is normally 60% saturated; although saturations may differ in two twins affected by severe TTTS, both would inevitably have a deeper colour than fetal venous blood typically at 80% saturation. The clinical data for this case provided sufficient detail to enable a computer model to be adjusted to match. We extended the placental detail of our previous model and ‘‘lasered’’ various vessels within it until the phenomenon was reproduced. METHODS Modelling technique The model used was based on our previous report [9] which details the methodology and relationships between hydrostatic and osmotic pressures and their relation in turn to various possible anastomotic configurations. For this study, each placenta was effectively divided into major and minor sectors, the major retaining much of the original code and the minor a more detailed version shown in Figure 2. Three generations of chorionic arteries feed sets of four cotyledons of each placenta, which are drained by three generations of chorionic veins. An AVA can be introduced between these sectors by causing a cotyledon from twin A to drain into the same third generation chorionic vein in placenta B as one of its own cotyledons. ‘‘Water columns’’ are connected to various significant points of the model to provide visualisation of pressures as they change when adjustments are
made. Provision was made for the operator to ‘‘laser’’ (occlude) various vessels to block flow through them. Experimental design The initial stage was to investigate any combination of connections that could induce blood that had passed through a cotyledon to appear in an AAA. This was unsuccessful as no configuration was found in which villus pressure could be raised to equal that in an AAA in order to bring oxygenated blood up into an AAA. The AAA was then removed and an interconnection pattern derived from the staging data installed. Bermudez et al. give their own proposed staging definitions on which the patient rated stage III TTTS. According to this definition, donor urine output is usually absent, or reduced so much that the bladder is not visible, and umbilical artery Doppler showed absence of end-diastolic flow. Cessation of urine production thus indicates that the donor’s mean arterial pressures were lower than normal. Conversely, in the recipient, the atrial natiuretic peptide mediated polyuria and hence polyhydramnios indicated raised intracardiac pressures. These features are associated with AVAs in only one direction and no AAA to allow return flow. In our model, we therefore introduced a single AVA between the twins which is the simplest connection preventing urine production in the donor. Figure 2a represents the hypothesised condition of this patient before treatment. RESULTS ‘‘Lasering’’ the interconnecting vessel (blue dot, Figure 2b) allowed all pressures to return to normal, except those associated with the donor cotyledon (A4) whose venous return vessel previously formed the AVA link. The pressure and flow changes are illustrated in Figure 3. Before laser (Figures 2a, 3a), pressure in the chorionic artery driving blood towards the
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cotyledon (Pchora2A2) in Figure 3a is always higher than that at entry to the cotyledon (PcotaA4) and so flow (dQchora3A4), although pulsatile, is always into cotyledon A4. When the communicating vessel was occluded (Figure 2b), blood could no longer escape from A4, and its intravillous pressure, and hence stem vein pressure (PcotvA4), rose to its arterial mean pressure (Figure 3b, magenta). The Pchora2A2 and PcotaA4 pressure traces then gradually overlapped (Figure 3b) driving blood towards the cotyledon at systole and producing back flow in diastole. (This is a microversion of reverse enddiastolic flow in complete placentas occurring when placental resistance is pathologically increased.) In the final stable condition (Figure 3c), forward and reverse flows have become equal as the mean flow has to be zero. Although this reproduced the reciprocating flow seen endoscopically, it did not explain the changes in position along the artery reported to occur from moment to moment. Recently, a case was reported in which clotting occurred in a placental vein draining several AVAs, which had produced sudden onset of TTTS [10]. This drew attention to the possible hazards of loss of venous return in an AVA. The tertiary vein shared by cotyledon A4 in the donor and cotyledon B1 in the recipient (Figure 2c) was ‘‘lasered’’ instead of the connecting vessel. Because the blood in cotyledons A4 and B1 then had no return path, their internal (villous) pressures (Pcotv4, Pcotv1, Figure 2c) rose to the mean pressure at the bifurcation of the second generation chorionic arteries supplying cotyledons 3 and 4 of the donor’s placenta and cotyledons 1 and 2 of the recipient’s placenta. The mean pressure at the bifurcation then rose, eventually falling and rising above that in the donor’s cotyledons 3 and 4, each cardiac cycle, producing a reciprocating flow superficially similar to that in genuine AAAs (Figure 3d). The high compliance of the cotyledons absorbs the pulsatile aspects of the pressures from the contralateral twin, so that each twin ‘‘sees’’ a cotyledon whose venous pressure is similar to its own arterial pressure, and reciprocating arterial flow developed as before. But now cotyledons A4 and B1 are connected in series between the two chorionic artery networks and any small change in cardiac output in either twin will produce a change in umbilical artery pressure which will in turn produce a net displacement of blood in the communicating vessel. This may displace the HE in the chorionic artery of the donor (in the donor’s territory) as described by Bermudez et al. If this unidirectional flow is from recipient to donor, the
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HE can be carried back to the first branch and the artery may appear permanently bright red. If in the opposite direction, the HE disappears into the cotyledon, and the artery will appear normal dark red in colour. If reciprocation carries the HE up to the branch and back again, the interface between blood from the two fetuses will be sharp and approximately transverse as they describe. DISCUSSION Using a computer model, it has been possible to reproduce the critical features of the reported apparent AAA equator at fetoscopy, without introducing a true AAA, namely: (1) a reciprocating boundary between dark red blood from one fetus and bright red blood from the other fetus, (2) occurrence in an artery within the donor’s territory, and (3) a slow displacement of this boundary towards or away from a branch artery. The key to the phenomenon is loss of a local venous return path. This might arise naturally [10] or as a result of intentional laser ablation of an AVA. But since the flow along this pseudoanastomosis necessarily has to pass through two cotyledons, it will be very much smaller than that mediating the protective haemodynamic effects of a true low resistance AAA. Hence, we term this high resistance path a pseudo-AAA (PAAA). Bermudez et al.’s contention that AAAs do not protect against haemodynamic imbalance in MC twins might be due to their misidentification of such chorionic arteries as AAAs on the basis of reciprocating flow. Endoscopically, if reciprocating flow brings bright red blood into the artery under investigation, the colour indicates that it obviously cannot be a genuine AAA. Ultrasonically, the two vessels can easily be distinguished by fundamental differences in Doppler waveforms. This results from the smoothing out of arterial flow pulsatility as blood passes through the two cotyledons forming the link in the PAAA. Thus, in a PAAA only the ipsilateral systolic peak will be seen, whereas in a genuine AAA, the systoles of both fetuses, one upwards and one downwards, will be seen, with a cyclic fluctuating pattern at the difference in frequency of the two fetal hearts. We and others (Hecher, personal communication) have not seen this HE/pseudo-AAA pattern at endoscopy. This may relate to differences in laser technique, as this pattern will not arise when both the arterial and the venous ends of an AVA are lasered and completely ablated.
Figure 2. The diagram represents minor segments of the placentas of the ‘‘donor’’ (‘‘A’’ left) and the ‘‘recipient’’ (‘‘B’’ right). Some of the more significant pressures are represented as if water columns were connected to them, to permit visualisation. The height of the columns is adjusted by the model as it runs. The starting point in (a) shows the model set up to represent part of a monochorial placenta in TTTS. The connecting AVA runs from the third generation chorionic artery feeding the fourth cotyledon from the left in the donor placenta (Pcota4), through that cotyledon to its stem vein (Pcotv4), across to the stem vein of cotyledon 1 of the recipient (Pcotv1) and down through the third generation vein in the recipient’s placenta which also drains the recipient cotyledon 1 to the second generation vein Pchorv2. Pressures in the donor have fallen and pressures in the recipient have risen until there is little average flow along the AVA. In (b) the connecting vessel has been lasered (blue spot). Pressures in both fetuses have started to normalise generally, except in the fourth cotyledon of the donor whose drainage path has been blocked. It fills to the ex-donor’s mean chorionic artery pressure at Pchora2, and as the instantaneous pressure Pchora2 rises and falls past the mean pressure held at Pcota4, flow reverses in the third generation artery Pcota4 to Pchora2. In (c) the third generation vein that was providing the common drainage for the connected cotyledons has been lasered. Here, pressure in both cotyledons rises to arterial values and there is in fact a path from the umbilical artery of one fetus, through the two cotyledons, and out to the umbilical artery of the other fetus.
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(a)
(b)
(c)
(d) Figure 3. Pressures corresponding to conditions in Figure 2a are shown in (a). Flow in the third generation chorionic artery feeding cotyledon A4 (dQchora3A4) shown before lasering in (a), immediately following lasering (b), and after flow stabilisation in (c). The pressure driving blood into it (from the second generation chorionic artery (Pchora2A2)) is shown above in the red trace, and the pressure it produces at the cotyledon’s stem artery (PcotaA4) in magenta. Cotyledons A4 and B1 are modelled as being close and so pressures at the cotyledon stem veins, PcotvA4 and PcotvB1, are virtually the same before the AVA is occluded. Before the AVA is occluded, Pchora2A2 is always greater than PcotaA4 and so flow into cotyledon A4 is unidirectional throughout the cardiac cycle. When the AVA is occluded, (b) blood has no path to leave the donor’s cotyledon 4 and accumulates, revealed as a steadily rising pressure in its stem vein (PcotvA4), whereas the loss of this supplementing flow causes a drop in cotyledon B1 stem vein pressure (PcotvB1). As blood accumulates in cotyledon A4, the resulting back pressure (PcotaA4) rises above that in Pchora2A2 for part of the cardiac cycle, causing the flow (dQchora3A4) to reverse whenever the two pressures cross. It then becomes increasingly bi-phasic until it settles to a balanced pattern (c) whose outline follows that of the driving pressure in the donor’s chorionic artery. A true AAA waveform is shown in (d) for comparison. At different parts of the ‘‘beat’’ cycle, the steep fronted systolic peaks of each umbilical artery pressure appear as mirror images of each other. In the PAAA flow pattern, there is only one set of steep fronted systolic peaks (c).
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ACKNOWLEDGEMENTS The authors thank the Richard and Jack Wiseman Trust for financial support, and Sport Aiding Research into Kids (SPARKS) and Children Nationwide Medical Research Fund for equipment support.
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