Progressive Dilatation of the Main Pulmonary Artery Is a Characteristic of Pulmonary Arterial Hypertension and Is Not Related to Changes in Pressure

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1 CHEST Originl Reserch PULMONARY ARTERIAL HYPERTENSION Progressive Dilttion of the Min Pulmonry Artery Is Chrcteristic of Pulmonry Arteril Hypertension nd Is Not Relted to Chnges in Pressure Brt Boerrigter, MD ; Gert-Jn Muritz, MSc ; J. Tim Mrcus, PhD ; Frnk Heldermn, MSc ; Pieter E. Postmus MD, PhD, FCCP ; Nico Westerhof, PhD ; nd Anton Vonk-Noordegrf, MD, PhD Bckground: Pulmonry rtery (PA) dilttion is one of the consequences of pulmonry rteril hypertension (PAH) nd is used for noninvsive detection. However, it is uncler how the size of the PA behves over time nd whether it is relted to pressure chnges. The im of this study ws to evlute PA size during follow-up in treted ptients with PAH nd whether it reflects pulmonry vsculr hemodynmics. Methods: Fifty-one ptients with PAH who underwent t lest two right-sided hert ctheteriztions (RHCs) together with crdic MRI (CMR) were included in this study. Another 18 ptients who hd norml pressure t RHC were included for comprison t bseline. From RHC, we derived PA pressures nd crdic output. From the CMR imges we derived PA dimeter (PAD) nd the rtio of the PAD nd scending ort dimeter. Results: The PAD ws significntly lrger in ptients with PAH thn in ptients without PAH ( P,.001). A rtio of the PAD nd scending ort dimeter. 1 hd positive predictive vlue of 92% for PAH. Men follow-up time ws 942 dys, nd there ws significnt dilttion during this period ( P,.001). The chnge of the PAD did not correlte with the chnges in pressure or crdic output. A moderte correltion with follow-up time ws found ( r ; P,.001). Conclusions: A diltted PA is useful for identifying ptients with PAH. However, during ptient follow-up, progressive dilttion of the PA is independent of the chnge in PA pressure nd crdic output nd might become independent from hemodynmics. CHEST 2010; 138(6): Abbrevitions: AA 5 scending ort; AAD 5 scending ort dimeter; CMR 5 crdic MRI; CO 5 crdic output; CSA 5 cross-sectionl re; dpap 5 distolic pulmonry rtery pressure; mpap 5 men pulmonry rtery pressure; PA 5 pulmonry rtery; PAD 5 pulmonry rtery dimeter; PAH 5 pulmonry rteril hypertension; PCWP 5 pulmonry cpillry wedge pressure; PVR 5 pulmonry vsculr resistnce; RHC 5 right-sided hert ctheteriztion; rpad/aad 5 rtio of the pulmonry rtery dimeter nd scending ort dimeter Pulmonry rteril hypertension (PAH) is clinicl syndrome chrcterized by n increse in pulmonry vsculr resistnce (PVR) leding to right-side hert filure nd, ultimtely, deth. 1 Dignosis erly in the course of the disese is difficult becuse of its nonspecific nture nd symptoms, such s dyspne, exercise intolernce, nd ftigue. Severl secondry effects of bnormlly elevted pulmonry rtery pressure (PAP) on right-sided structures, such s pulmonry rtery (PA) dilttion nd right ventriculr hypertrophy, my be helpful in the dignosis of PAH. PA dimeter (PAD) cn be obtined noninvsively nd is, therefore, one of the prmeters in PAH tht hs been studied throughout the yers. Erly investigtors found through chest rdiogrphy resonble correltions between right descending PAD nd PAP.2 After the introduction of helicl CT imging, severl studies hve been performed to mesure the PAD nd showed tht n incresed min PAD is relible indictor of PAH, especilly when the rtio of PAD nd scending ort dimeter (rpad/aad) is used. 3-9 More recently, using crdic MRI (CMR), vrious uthors showed tht PAD or rpad/aad is useful in the noninvsive detection of PAH. On the bsis of these studies, it cn be concluded tht PAD or rpad/aad is useful in the noinvsive detection of CHEST / 138 / 6 / DECEMBER,

2 PAH, but correltions of dimeter nd pressure vry considerbly mong the studies possibly becuse of differences in study popultions Although PAP is supposed to be the driving force to dilte the PA, the influence of other prmeters, such s time nd flow, is unknown. In ddition, it is unknown whether the chnges in PAP re followed by similr chnge in PAD. Therefore, the im of this study is to investigte whether chnge in PAD over time reflects chnges in pressure, crdic output (CO), or both in ptients with PAH. Study Group Mterils nd Methods This study is prt of lrge prospective study imed to evlute the role of MRI in PAH. This study hs institutionl reserch bord pprovl, nd ll ptients gve informed consent to the procedures. Fifty-six ptients with PAH were initilly included in our study. All hd bseline evlution before the strt of therpy nd follow-up evlution of therpy t lest 8 months fter. Ech evlution consisted of right-sided hert ctheriztion (RHC) nd CMR mesurement seprted on verge 2 dys from ech other. In five ptients, the qulity of one of the MRI imges did not permit mesurement becuse of respirtory rtifcts. Consequently, 51 ptients with PAH were included this study. All ptients were clssified in group 1 of the clinicl clssifiction of PAH, 15 with 41 hving idiopthic PAH; nine, collgen vsculr disese-ssocited PAH; nd one, HIV-ssocited PAH. During follow-up, ptients were treted ccording to the stndrd in PAH ( Tble 1 ). Additionlly, for bseline nlysis, we included 18 ptients suspected of hving PAH who underwent RHC nd MRI once but hd norml PAP t RHC (ie, normotensive ptients). CMR Protocol In this study, we used CMR imges tht were prt of the routine clinicl evlution of the ptients or prt of former studies in this center. CMR ws performed with either Siemens 1.5 T Sont or Avnto (Siemens Medicl Solutions; Erlngen, Germny) whole-body scnner equipped with phsed-rry body coil. PAD ws ssessed from mgnitude imges used for phsecontrst imging becuse these imges were ssessed in ll ptients in this retrospective study ( Fig 1 ). The imge plne for Mnuscript received Februry 8, 2010; revision ccepted April 20, Affilitions: From the Deprtments of Pulmonry Diseses (Drs Boerrigter, Postmus, Westerhof, nd Vonk-Noordegrf nd Mr Muritz), Physics nd Medicl Technology (Dr Mrcus nd Mr Heldermn), nd Physiology (Dr Westerhof), Institute for Crdiovsculr Reserch, VU University Medicl Center, Amsterdm, The Netherlnds. Dr Boerrigter nd Mr Muritz contributed eqully to this rticle. Funding/Support: Dr Vonk-Noordegrf ws supported by the Netherlnds Orgnistion for Scientific Reserch (NWO)-VIDI (project number ). Correspondence to: Anton Vonk-Noordegrf, MD, PhD, VU University Medicl Center, PO Box 7057, 1007 MB Amsterdm, The Netherlnds; e-mil:.vonk@vumc.nl. Reproduction of this rticle is prohibited without written permission from the Americn College of Chest Physicins ( site/misc/reprints.xhtml ). DOI: /chest mesuring the scending ort (AA) ws determined s follows: A set of coronl loclizer imges ws cquired, nd then the imge tht showed the AA ws selected. On this coronl imge, set of xil imges ws cquired tht intersected the AA. From these xil imges, the imge ws selected tht showed the AA in circulr cross section. This xil plne ws t the level of the right PA. During the follow-up cquisition, position of the orthogonl slice of the min PA t bseline mesurements ws used for positioning the orthogonl slice t follow-up of the min PA to minimize differences in mesurement locliztion from bseline. RHC Protocol RHC ws performed with blloon, flow-directed 7F Swn- Gnz ctheter. The ptients were in stble condition, lying supine nd brething room ir, while hert rte ws continuously monitored. Mesurements were mde of men right tril pressure, right ventriculr pressure, systolic PAP, distolic PAP (dpap), men PAP (mpap), nd pulmonry cpillry wedge pressure (PCWP). CO obtined by either thermodilution or direct Fick method from rteril nd mixed venous oxygen sturtion nd oxygen consumption. Afterwrd, PVR ws clculted s (mpap 2 PCWP)/CO. The medin intervl from CMR to RHC ws 2 dys (rnge, 2-21 dys). Imge Anlysis In the mgnitude imges, the wll of the PA is utomticlly detected. A semiutomtic wll detection progrm, bsed on study published by Li et l 16 using Mtlb R2008 (The Mth- Works; Ntick, MA) ws used to cquire more-ccurte mesurements of the PA, reduce opertor bis, nd minimize detection difficulties due to low signl intensity during distole. Cross-sectionl res (CSAs) were obtined through the entire crdic cycle (25-60 imges) nd visully checked by the opertor. The miniml CSA ws considered the distolic CSA. From the CSA of this contour, the verge dimeter ws clculted nd used in this study. For scling to ort size, we mesured the AAD in the sme wy s the PAD t end distole t the level of the PA bifurction. All nlyses were performed by one investigtor who ws unwre of RHC results. Ten ptients were rndomly selected for repeted mesurements by both the first investigtor nd second blinded investigtor in order to test intr- nd interobserver vribility. Sttisticl Anlyses Hemodynmic vlues re presented s men 6 SDs or medin (interqurtile rnges). Differences between ptient groups were evluted with n independent-smple t test or Mnn- Whitney U test when not normlly distributed. The bility of the rpad/aad to predict PAH ws tested using receiver operting chrcteristic curve. Differences between bseline nd follow-up where evluted with pired-smple t test. For nlysis of tertile differences, one-wy nlysis of vrince with post hoc Bonferroni correction ws used. Intr- nd interobserver greement ws ssessed by Blnd-Altmn nlysis. All tests were two-tiled, nd P,.05 ws considered significnt. Anlyses were performed with sttisticl softwre SPSS for Windows, version (SPSS Inc; Chicgo, IL). RHC Results Results RHC mesurements confirmed the dignosis of PAH in the 51 study ptients nd norml pressures in 1396 Originl Reserch

3 Tble 1 Tretment of the 51 Ptients With Pulmonry Arteril Hypertension Tretment No. of Ptients Ambrisentn 2 Bosentn 36 Sitxentn 11 Clcium chnnel blocker 3 Sildenfil 41 Epoprostenol (IV) 20 Treprostenil (subcutneous) 13 Iloprost (inhled) 1 The totl number of tretments exceeds the number of ptients, indicting combined tretment or chnges in tretment. the 18 normotensive ptients. The demogrphic nd hemodynmic chrcteristics obtined t RHC of both ptients groups re shown in Tble 2. As expected, mpap, systolic PAP, dpap, men right tril pressure, PVR nd hert rte t RHC were significntly higher in ptients with PAH thn in the normotensive ptients. In ddition, CO, crdic index, stroke volume, nd mixed venous oxygen sturtion were significntly lower in ptients with PAH. Between the study groups, there were no significnt differences in terms of sex distribution, body surfce re, rteril oxygen sturtion, or PCWP. The normotensive ptients were significntly older thn the ptients with PAH. Figure 1. A-C, Stedy-stte free precession crdic MRI (CMR) imges to loclize the pulmonry trunk (repetition time/echo time, 3.2/1.6 ms; flip ngle, 65 ; section thickness, 6 mm; mtrix, ). A, An imge ws prescribed perpendiculr to trnsversl view tht included the PA. B, An oblique-sgittl imge results. C, A third loclizer imge ws cquired ccording to the stright line in B nd used together to obtin the imge plne for the throughplne velocity mesurement in the min PA. D, The cross section of the min PA cquired s the mgnitude imge in the flow mesurement ws obtined with grdient-echo sequence with through-plne phse-contrst velocity quntifiction (see text for detils). In ddition, A shows the plne orthogonl to the AA in which the ortic dimeter is mesured is used for normliztion of the PA size with respect to the ort. AA 5 scending ort; PA 5 pulmonry rtery. PAD nd Pressure The distolic PAD ws significntly lrger in ptients with PAH thn in normotensive ptients ( Tble 2 ). In the entire group t bseline, the correltion coefficient between PAD nd mpap ws 0.58 ( P,.001) ( Fig 2A ). In ll ptients with PAH, there ws only wek, but significnt reltion ( r ; P 5.04) between PAD nd mpap. A significnt difference ws found between the rpad/aad in the PAH group nd normotensive group. In the entire group, the correltion coefficient of rpad/aad with mpap ws 0.71 ( P,.001) ( Fig 2B ). Agin, for ptients with PAH, the reltion between rpad/aad nd dpap ws wek ( r ; P,.001). The correltion coefficient of rpad/aad with dpap ws 0.69 ( P,.001). The re under the receiver operting chrcteristic curve for the rpad/aad in the detection of PAH ws 0.93 (CI, ) ( Fig 3 ). The optiml rpad/aad ws 1.1, with sensitivity of 80% nd specificity of 94%. For n rpad/aad of 1, we found sensitivity of 92%, specificity of 72%, nd positive predictive vlue of 92%. Chnges of PAD During Follow-up Men follow-up time ws 942 dys (rnge, 242-2,359 dys). During follow-up, the PAD incresed significntly ( Tble 3 ). In 37 (73%) ptients with PAH, the dimeter incresed (men, mm; rnge, mm). In 11 (22%) ptients, the dimeter decresed (men, mm; rnge, mm). In three ptients, the dimeter remined unchnged. PVR decresed, nd CO incresed, both significntly, under tretment during follow-up ( Tble 3 ). Figure 4 shows plot of the chnge of PAD ginst the chnge in mpap. Of the 11 ptients with decresed dimeter, only three hd decrese. 2 mm. The mpap in these three ptients ws normlized or lmost normlized under tretment; the mpap t follow-up rnged from 15 to 28 mm Hg. In ptients with n incresed PAD t follow-up, the pressure either incresed or decresed, nd no reltion ws found between PAD chnge nd pressure chnge. Figure 5 shows tht there were no significnt differences between tertiles regrding CO, mpap t bseline, nd PAD t bseline. In contrst, dimeter chnge cross tertiles of follow-up time differed significntly for the outermost tertiles, wheres the chnges in CO nd mpap were not different over the tertiles. Overll, moderte correltion between follow-up time nd dimeter chnge ws found ( r ; P,.001). Neither reltion between chnges in PAD nd pulse pressure t bseline ( r ; P 5.14) nor reltion between chnges in PAD nd pulse pressure chnges during follow-up ( r ; P 5.27) ws found. CHEST / 138 / 6 / DECEMBER,

4 Tble 2 Bseline Hemodynmic nd Demogrphic Chrcteristics Prmeter Totl Ptients With PAH Normotensive Ptients P Vlue Ptients, No Age, y Femle ptients, No. (%) 53 (77) 38 (75) 15 (83) ns Body surfce re, m ns Hert rte, bets/min Systolic PAP, mm Hg ,.001 Distolic PAP, mm Hg ,.001 Men PAP, mm Hg ,.001 PCWP, mm Hg ns PVR, dynes/s/cm ,.001 Men right tril pressure, mm Hg ,.001 Right ventriculr distolic pressure, mm Hg ,.001 CO, L /min ,.001 Crdic index, L /min/m ,.001 Stroke volume, ml ,.001 Arteril oxygen sturtion, % ns Mixed venous oxygen sturtion, % PAD, mm ,.001 AAD, mm rpad/aad ,.001 Dt re presented s men 6 SD or medin (interqurtile rnge), unless otherwise indicted. AAD 5 scending ort dimeter; CO 5 crdic output; ns 5 not significnt; PAD 5 pulmonry rtery dimeter; PAH 5 pulmonry rteril hypertension; PAP 5 pulmonry rtery pressure; PCWP 5 pulmonry cpillry wedge pressure; PVR 5 pulmonry vsculr resistnce; rpad/aad 5 rtio of the PAD nd AAD. Between PAH group nd normotensive group. Reproducibility of PAD Mesurements Although the detection of the PAD is semiutomtic nd the progrm used reduces opertor bis, intr- nd interobserver vribility ws checked. Blnd-Altmn nlysis reveled n introbserver bis of mm nd n interobserver vribility bis of mm, showing good reproducibility of PAD mesurements. Discussion In this study, we show tht PAD nd rpad/aad re useful in discriminting ptients with PAH from ptients without PAH. This finding is in line with previous reports. However, during follow-up, most PAs showed progressive dilttion, which is not relted to the chnges in pressure. Furthermore, we found tht the chnge in PAD ws not relted to chnges in flow. PAD nd Pressure Our results showed tht the distolic PAD hs dignostic vlue in PAH. We chose the distolic dimeter becuse it is the customry choice in CT imges. The dimeters used were verged dimeters derived from the CSA. There ws no difference in the reltion of rpad/aad with dpap nd mpap, which cn be explined by the strong proportionl reltion between dpap nd mpap. 17,18 The mpap ws used in this study becuse dignosis customrily is bsed on it. As seen in prior studies, we found tht n Figure 2. Grphs showing the results of regression nlysis in the study group. A, PAD vs mpap. B, Rtio of PAD nd AAD vs men PA pressure. 5 normotensive ptients; 5 ptients with PA hypertension; AAD 5 scending ort dimeter; mpap 5 men pulmonry rtery pressure; PAD 5 pulmonry rtery dimeter. See Figure 1 for expnsion of the other bbrevition Originl Reserch

5 Figure 4. Chnge in PAD ginst the chnge in mpap, indicting the chnge in pressure nd dimeter between right-sided hert ctheteriztion nd CMR evlution in 59 ptients. Four ptients (highlighted) showed decrese in dimeter of. 2 mm. In ll four ptients, the pressure ws (lmost) normlized during follow-up. DmPAP 5 chnge in mpap. See Figure 1 nd 2 legends for expnsion of the other bbrevitions. Figure 3. The receiver operting chrcteristic curve of the bility of the rtio of PAD nd AAD to detect n mpap of. 25 mm Hg. AUC 5 re under the curve. See Figure 1 nd 2 legends for expnsion of the other bbrevitions. enlrged PAD is relted to the presence of PAH nd, thus, cn be used in the detection of PAH. We found tht n rpad/aad. 1.1 yields the highest dignostic ccurcy. The use of the rpad/aad lso is recommended becuse its reltionship with PAP is independent of body surfce re nd sex. 5 This cutoff point of 1.1 is different from erlier studies tht found tht rtio of 1 is the best dignostic cut-off point. The explntion of this discrepncy might be tht these studies used 20 mm Hg of mpap s the dignostic criterion for PAH insted of the currently used criterion of 25 mm Hg. 1 However, if we pply the cut-off point of 1.0, resonble sensitivity of 92% nd specificity of 72% were found. The dignostic ccurcy of the rpad/aad might be overestimted becuse there is reltively lrge hitus in the levels of mpap between the normotensive ptients nd this well-defined group of ptients with PAH. In Tble 3 Hemodynmic Chrcteristics nd PAD t Bseline nd Follow-up Prmeter Bseline Follow-up P Vlue PAD, mm Men PAP, mm Hg CO, L /min Hert rte, bets/min Stroke volume, ml PVR, dynes/s/cm Ptients, n 5 51; men follow-up time, 942 dys (rnge, 224-2,359 dys). See Tble 2 for expnsion of bbrevitions. Pired-smple t test. this study group, there were no ptients with ortic bnormlities or systemic hypertension, which could ffect the size of the AA nd clerly could ffect the relibility of the rpad/aad. Chnges of PAD During Follow-up During follow-up, the PA dilted in most of the ptients. The chnges of the PAD between the two CMR mesurements did not reflect chnges in mpap between the corresponding RHCs. In ll the ptients in whom the pressure ws higher thn initilly, the PAD hd incresed. However, if the pressure ws lower thn initilly, the mjority of this group s PADs still incresed. Only in three ptients did the PAD decrese. 2 mm; in ll these ptients, the pressure ws normlized or lmost normlized. Thus, progressive dilttion ws found in the ptients with PAH, which ws not explined by pressure chnges. Even in the mjority of the ptients in which the pressure decresed, there ws n ongoing dilttion of the PA. Figure 5A suggests tht PA with lrge dimeter t bseline tends towrd greter dilttion during follow-up. It seems logicl tht if dilttion during follow-up becomes independent of hemodynmics, lrger dimeter t bseline will led to lrger dilttion during the follow-up. However, this reltion ws not found to be sttisticlly significnt. The finding tht neither pressure nor flow re relted to the progressive dilttion in most of the ptients shows tht other explntions thn chnges in pulmonry hemodynmics underlie this progressive dilttion, phenomenon well-known from neurysms of the ort. Although systemic hypertension CHEST / 138 / 6 / DECEMBER,

6 ws lredy present for long period. Third, our dt indicte tht lthough incresed PAP leds to diltion of the PA, further diltion is process most likely due to chnge of the intrinsic vessel properties, which is independent of the pulmonry hemodynmics. Limittions Figure 5. A, Dimeter chnge ginst the different tertiles of PAD t bseline. B, mpap t bseline. C, Chnges in crdic output. D, Durtion of follow-up. See Figure 1 nd 2 legends for expnsion of the other bbrevitions. is n importnt underlying cuse of this disese, further dilttion of the ort in neurysms is independent of systemic BP. 19 The min question ws to investigte whether during follow-up chnges in PA dilttion exist nd whether they re relted to chnges in pressure. For this reson, we did not evlute specific other hemodynmic prmeters s possible explntions for chnges in PAD. Nevertheless, we found tht the dimeter increse did not correlte with ge, use of epoprostnol, nd pulstility in PAD. Absence of direct reltion between chnges in pressure or flow nd chnges in dimeter does not exclude tht incresed PAP or reduced flow is the cuse of PA dilttion. Although there is n bsence of rdiologic studies investigting the structure of the PA wll, recent histologic studies of the proximl prts of the PAs provide evidence tht significnt remodeling of the proximl PA wll occurs in PAH. 20,21 Structurl chnges in elstin nd collgen under the influence of n incresed PAP might eventully become cuse of PA dilttion, irrespective of chnges in pressure nd flow. In ddition, ltered flow in PAH ffects wll sher stress nd, subsequently, mtrix properties of the vessel wll 22 tht might led to PA dilttion. Clinicl Implictions Our findings hve severl clinicl implictions. First, the PAD, lthough useful in the dignosis of PAH, is not useful for follow-up of the disese or evlution of tretment effects. Second, we show tht the dilttion of the PA in PAH is more relted to follow-up time thn to pressure chnge, indicting tht the PA needs time to dilte. A severe dilted PA t the time of dignosis thus indictes tht the PAH There re some study limittions tht might hve influenced our results. First, pressure nd CMR mesurements could not be performed simultneously for logistic nd ptient resons nd might hve ffected the strength of the ssocitions we found. However, given the verge time of follow-up (942 dys), it is unlikely tht medin intervl of 2 dys between RHC nd CMR mesurements ffected the conclusions. Second, given the conus-shped min PA, differences in level of imge cquisition on the different time points might hve creted bis. We tried to overcome this limittion by using n experienced investigtor to cquire ll CMR imges nd by using reference points cquired t the bseline mesurement during the follow-up mesurement. In conclusion, in ptients with PAH, the rpad/ AAD cn be used for the detection of PAH. During follow-up, dilttion of the PA does not reflect chnges in pressure or flow; therefore, chnges in PAD cnnot be used in clinicl prctice for the evlution of the course of the disese, therpeutic response, or estimtion of pressure. Acknowledgments Author contributions: Dr Boerrigter: contributed to study design, mnuscript preprtion nd revision, dt collection, nlysis, nd interprettion. Mr Muritz: contributed to study design, mnuscript preprtion nd revision, dt collection, nlysis, nd interprettion. Dr Mrcus: contributed to dt nlysis. Mr Heldermn: contributed to dt nlysis. Dr Postmus: contributed to mnuscript revision. Dr Westerhof: contributed to study design, dt interprettion, nd mnuscript revision. Dr Vonk-Noodegrf: contributed to study design, dt interprettion, nd mnuscript revision. Finncil/nonfinncil disclosures: The uthors hve reported to CHEST tht no potentil conflicts of interest exist with ny compnies/orgniztions whose products or services my be discussed in this rticle. References 1. McLughlin VV, Archer SL, Bdesch DB, et l ; Americn College of Crdiology Foundtion Tsk Force on Expert Consensus Documents ; Americn Hert Assocition ; Americn College of Chest Physicins ; Americn Thorcic Society, Inc ; Pulmonry Hypertension Assocition. ACCF/AHA 2009 expert consensus document on pulmonry hypertension report of the Americn College of Crdiology Foundtion Tsk Force on Expert Consensus Documents nd the Americn Hert Assocition developed in collbortion with the Americn College of Chest Physicins; Americn Thorcic Society, 1400 Originl Reserch

7 Inc.; nd the Pulmonry Hypertension Assocition. J Am Coll Crdiol ; 53 ( 17 ): Teichmnn V, Jezek V, Herles F. Relevnce of width of right descending brnch of pulmonry rtery s rdiologicl sign of pulmonry hypertension. Thorx ;25 (1 ): Himovici JB, Trotmn-Dickenson B, Hlpern EF, et l ; Msschusetts Generl Hospitl Lung Trnsplnttion Progrm. Reltionship between pulmonry rtery dimeter t computed tomogrphy nd pulmonry rtery pressures t rightsided hert ctheteriztion. Acd Rdiol ;4 (5 ): Kuriym K, Gmsu G, Stern RG, Cnn CE, Herfkens RJ, Brundge BH. CT-determined pulmonry rtery dimeters in predicting pulmonry hypertension. Invest Rdiol ; 19 (1 ): Ng CS, Wells AU, Pdley SPA. A CT sign of chronic pulmonry rteril hypertension: the rtio of min pulmonry rtery to ortic dimeter. J Thorc Imging ;14 (4 ): Schmidt HC, Kuczor HU, Schild HH, et l. Pulmonry hypertension in ptients with chronic pulmonry thromboembolism: chest rdiogrph nd CT evlution before nd fter surgery. Eur Rdiol ;6 (6 ): Heinrich M, Uder M, Tscholl D, Grgic A, Krmnn B, Schäfers HJ. CT scn findings in chronic thromboembolic pulmonry hypertension: predictors of hemodynmic improvement fter pulmonry thromboendrterectomy. Chest ; 127 (5 ): Moore NR, Scott JP, Flower CD, Higenbottm TW. The reltionship between pulmonry rtery pressure nd pulmonry rtery dimeter in pulmonry hypertension. Clin Rdiol ;39 (5 ): Grubstein A, Benjminov O, Dyn DB, Shitrit D, Cohen M, Krmer MR. Computed tomogrphy ngiogrphy in pulmonry hypertension. Isr Med Assoc J ;10 (2 ): Frnk H, Globits S, Glogr D, Neuhold A, Kneussl M, Mlczoch J. Detection nd quntifiction of pulmonry rtery hypertension with MR imging: results in 23 ptients. AJR Am J Roentgenol ;161 (1 ): Murry TI, Boxt LM, Ktz J, Regn K, Brst RJ. Estimtion of pulmonry rtery pressure in ptients with primry pulmonry hypertension by quntittive nlysis of mgnetic resonnce imges. J Thorc Imging ;9 (3 ): Snz J, Kriis M, Dellegrottglie S, et l. Evlution of pulmonry rtery stiffness in pulmonry hypertension with crdic mgnetic resonnce. JACC Crdiovsc Imging ; 2 (3 ): Snz J, Kuschnir P, Rius T, et l. Pulmonry rteril hypertension: noninvsive detection with phse-contrst MR imging. Rdiology ;243 (1 ): Bouchrd A, Higgins CB, Byrd BF III, Ampro EG, Oski L, Axelrod R. Mgnetic resonnce imging in pulmonry rteril hypertension. Am J Crdiol ;56 (15 ): Gliè N, Hoeper MM, Humbert M, et l ; ESC Committee for Prctice Guidelines (CPG). Guidelines for the dignosis nd tretment of pulmonry hypertension: the Tsk Force for the Dignosis nd Tretment of Pulmonry Hypertension of the Europen Society of Crdiology (ESC) nd the Europen Respirtory Society (ERS), endorsed by the Interntionl Society of Hert nd Lung Trnsplnttion (ISHLT). Eur Hert J ;30 (20 ): Li W, Von Birgelen C, Di Mrio C, et l. Semi-utomtic Contour Detection for Volumetric Quntifiction of Intrcoronry Ultrsound. Computers in Crdiology. Los Almitos, CA : IEEE Computers Society Press ; 1994 : Cheml D, Cstelin V, Humbert M, et l. New formul for predicting men pulmonry rtery pressure using systolic pulmonry rtery pressure. Chest ;126 (4 ): Syyed R, Reeves JT, Welsh D, Reside D, Johnson MK, Pecock AJ. The reltionship between the components of pulmonry rtery pressure remins constnt under ll conditions in both helth nd disese. Chest ; 133 ( 3 ): Brdy AR, Thompson SG, Fowkes FG, Greenhlgh RM, Powell JT ; UK Smll Aneurysm Tril Prticipnts. Abdominl ortic neurysm expnsion: risk fctors nd time intervls for surveillnce. Circultion ;110 (1 ): Kobs RW, Chesler NC. The mechnobiology of pulmonry vsculr remodeling in the congenitl bsence of enos. Biomech Model Mechnobiol ;5 (4 ): Lmmers SR, Ko PH, Qi HJ, et l. Chnges in the structure-function reltionship of elstin nd its impct on the proximl pulmonry rteril mechnics of hypertensive clves. Am J Physiol Hert Circ Physiol ; 295 ( 4 ): H H Botney Mitchell D. Role of hemodynmics in pulmonry vsculr remodeling: implictions for primry pulmonry hypertension. Am J Respir Crit Cre Med ;159 (2 ): CHEST / 138 / 6 / DECEMBER,