BACKGROUND: A recent study of human cadaveric renal arteries revealed that
      renal artery narrowing could be due not only to atherosclerotic plaque
      compensated for by adaptive remodeling, but also to hitherto undescribed
      focal narrowing of an otherwise normal renal arterial wall (ie,
      coarctation). The present study investigated whether vessel coarctation
      could be identified in patients with symptomatic renal artery stenosis
      (RAS). METHODS AND RESULTS: Consecutive symptomatic patients with
      angiographically proven atherosclerotic RAS who were referred for stent
      placement were studied by 30-MHz intravascular ultrasound before
      intervention (n=18) or after predilatation (n=18). Analysis included
      assessment of the media-bounded area and plaque area (PLA) at the most
      stenotic site and at a distal reference site (most distal cross-section in
      the main renal artery with normal appearance). Coarctation was considered
      present whenever the target/reference media-bounded area was </=85%.
      Before intervention, coarctation was observed in 9 of 18 patients and
      adaptive remodeling in 9 of 18 patients. Coarctation lesions had a
      significantly smaller PLA than adaptive remodeled lesions (P=0.001).
      Similarly, despite predilatation, coarctation was seen in 8 of 18 patients
      who had significantly smaller PLAs (P=0. 008) when compared with those
      patients who had adaptive remodeled lesions. No differences in severity of
      RAS or angiographic or clinical parameters were observed. CONCLUSIONS:
      Low-plaque coarctation may cause a considerable proportion of symptomatic
      RAS, which is angiographically and clinically indistinguishable from
      plaque-rich RAS

Deinum, J. (Jacob)

Dijk, L.C. (Lukas) van

Essen, J.A. (Anthonie) van

Gussenhoven, E.J. (Elma)

Honkoop, J.

Leertouwer, T.C. (Trude)

Pattynama, P.M.T. (Peter)

Erasmus University Digital Repository

ISSN: 1524-4539 Copyright © 1999 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online72514Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 1999;99;2976-2978 CirculationJan Honkoop, Jaap Deinum and Peter M. T. Pattynama Trude C. Leertouwer, Elma J. Gussenhoven, Lukas C. van Dijk, Jeroen A. van Essen, Artery StenosisIntravascular Ultrasound Evidence for Coarctation Causing Symptomatic Renal http://circ.ahajournals.org/cgi/content/full/99/23/2976located on the World Wide Web at: The online version of this article, along with updated information and services, is http://www.lww.com/static/html/reprints.htmlReprints: Information about reprints can be found online at    journalpermissions@lww.comStreet, Baltimore, MD 21202-2436. Phone 410-5280-4050. Fax: 410-528-8550. Email: Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, 351 West Camden   http://circ.ahajournals.org/subsriptions/Subscriptions: Information about subscribing to Circulation is online at  at SWETS SUBS SERVICE on December 5, 2006 circ.ahajournals.orgDownloaded from Intravascular Ultrasound Evidence for Coarctation CausingSymptomatic Renal Artery StenosisTrude C. Leertouwer, MSc; Elma J. Gussenhoven, MD;Lukas C. van Dijk, MD; Jeroen A. van Essen, MD; Jan Honkoop, BSc;Jaap Deinum, MD; Peter M.T. Pattynama, MDBackground—A recent study of human cadaveric renal arteries revealed that renal artery narrowing could be due not onlyto atherosclerotic plaque compensated for by adaptive remodeling, but also to hitherto undescribed focal narrowing ofan otherwise normal renal arterial wall (ie, coarctation). The present study investigated whether vessel coarctation couldbe identified in patients with symptomatic renal artery stenosis (RAS).Methods and Results—Consecutive symptomatic patients with angiographically proven atherosclerotic RAS who werereferred for stent placement were studied by 30-MHz intravascular ultrasound before intervention (n518) or afterpredilatation (n518). Analysis included assessment of the media-bounded area and plaque area (PLA) at the moststenotic site and at a distal reference site (most distal cross-section in the main renal artery with normal appearance).Coarctation was considered present whenever the target/reference media-bounded area was #85%. Before intervention,coarctation was observed in 9 of 18 patients and adaptive remodeling in 9 of 18 patients. Coarctation lesions had asignificantly smaller PLA than adaptive remodeled lesions (P50.001). Similarly, despite predilatation, coarctation wasseen in 8 of 18 patients who had significantly smaller PLAs (P50.008) when compared with those patients who hadadaptive remodeled lesions. No differences in severity of RAS or angiographic or clinical parameters were observed.Conclusions—Low-plaque coarctation may cause a considerable proportion of symptomatic RAS, which is angiographi-cally and clinically indistinguishable from plaque-rich RAS. (Circulation. 1999;99:2976-2978.)Key Words: renal artery n stenosis n hypertension n ultrasonography, interventionalIt is generally accepted that atherosclerotic plaque accumula-tion is the principal cause of renal artery stenosis (RAS).1,2 Arecent intravascular ultrasound (IVUS) study in human renalarteries obtained at autopsy, however, suggested an alternativecause of RAS.3 In that study, we observed that in 60% of thespecimens, plaque accumulation, with or without compensatoryvessel enlargement (ie, adaptive remodeling), caused lumennarrowing. This phenomenon was first described by Glagov etal4 and, subsequently, by others.5,6 In the remaining 40% of thespecimens, however, focal narrowing of the renal artery wallwith little or no plaque was observed. Here, we propose the term“coarctation” to describe the latter condition (Dorland’s MedicalDictionary defines coarctation as “a condition of stricture orcontraction”7).If this condition is present in vivo, it might cause hemo-dynamically significant RAS. However, to the best of ourknowledge, renal artery coarctation has not been describedbefore in vivo, especially not in patients with atheroscleroticrenal vascular disease. The first aim of the present study was,therefore, to establish whether renal artery coarctation couldbe identified as a contributing factor to RAS in symptomaticpatients with angiographically proven RAS. The second aimwas to identify angiographic and/or clinical variables thatmight be predictive for the distinguishing lesions.MethodsBetween September of 1996 and March of 1999, we studied 48consecutive patients (16 women and 32 men aged 5969 years[mean6SD]) with hypertension and/or renal function impairmentand atherosclerotic RAS who were referred for percutaneous trans-luminal stent placement guided by IVUS. Previous angiograms hadrevealed .50% diameter stenosis in all patients. The Local Com-mittee of Human Research approved the investigation. Patients wereincluded in the study after informed consent was obtained.Revascularization was performed via the femoral approach. Thestenosis was crossed with a 5F selective catheter in combination with0.035-in hydrophilic guidewire (Terumo). The hydrophilic wire wasexchanged for a 0.020-in stiff guidewire with a flexible tip (BostonScientific) for guiding the IVUS catheter, the angioplasty balloon,and the balloon-expandable stent. A 30-MHz mechanical IVUSimaging system was used with 4.3F catheters (“Princeps”, EndoSon-ics).8 The IVUS catheter was positioned distally from the stenosis inthe first major side branch. Real-time cross-sectional images of therenal artery wall obtained during slow pullback of the IVUS catheterReceived February 2, 1999; revision received April 6, 1999; accepted April 20, 1999.From the Departments of Radiology (T.C.L., L.C.v.D., P.M.T.P.), Internal Medicine (T.C.L., J.D.), and Cardiology (E.J.G., J.A.v.E., J.H.), the ErasmusUniversity Medical Center, Rotterdam, and the Interuniversity Cardiology Institute (E.J.G., J.A.v.E.), The Netherlands.Correspondence to Elma J. Gussenhoven, MD, Erasmus University Rotterdam (Ee 2312), Dr. Molewaterplein 50, 3000 DR Rotterdam, TheNetherlands. E-mail leertouwer@tch.fgg.eur.nl© 1999 American Heart Association, Inc.Circulation is available at http://www.circulationaha.org2976Brief Rapid Communicationswere displayed on a monitor and stored on S-VHS videotape foroff-line analysis.Image AnalysisFrom each renal artery, multiple IVUS cross-sections were quanti-tatively analyzed to select the target site and a reference site forfurther analysis. The target site was the IVUS cross-section with thesmallest lumen area. The reference site was the most distal cross-section in the renal artery truncus with a normal appearance.Analysis included assessment of lumen area (LA), media-boundedarea (MBA), plaque area (PLA), and percentage area stenosis. LAwas defined as the area encompassed by the inner boundary of theintimal surface. MBA was defined as the native vessel area boundedby the external elastic lamina. PLA was calculated by subtracting LAfrom MBA. Percentage area stenosis was calculated as the LA at thetarget site divided by the LA at the reference site.The MBA at the target site was expressed as a percentage of theMBA at the reference site. A relative MBA of .85% at the targetsite indicated a similar or larger MBA (“adaptive remodeling”group), and a relative MBA of #85% at the target site indicated asmaller MBA than at the reference site (“coarctation” group). On thebasis of our previous observation that renal artery tapering does notoccur,3 we used a 15%-tolerance interval to define a smaller MBA tobe on the conservative side. We assessed whether the conclusions ofthe quantitative analysis, which were performed by 2 independentobservers (T.C.L. and J.A.v.E.), were consistent for the observersindividually. Mean values of the 2 observers are given.Statistical AnalysisThe 2 groups were compared with regard to the MBA and PLA at thetarget and reference sites, relative MBA, and percentage areastenosis. Student’s t tests were used at the P,0.05 significance level.Interobserver variability for quantitative IVUS measurements wasquantified by regression analysis and a coefficient of variation,which was defined as the standard deviation of the paired differencedivided by the mean of the absolute value. Multivariate logisticregression analysis was performed to predict the presence of either ofthe 2 lesions.A logistic regression model was fitted using angiographic andclinical parameters as the independent variables. Angiographically, adistinction was made between ostial and truncal lesions.9 Depen-dence on the following clinical characteristics was assessed: age, sex,signs and symptoms of atherosclerotic vascular disease (anginapectoris, intermittent claudication, cerebrovascular accident, or vas-cular surgery), onset of hypertension (,1, 1 to 2, 2 to 5, or .5years), smoking history (ever or never), obesity (body mass index$25 kg/m2), serum creatinine concentration, and hypercholesterol-emia (serum cholesterol level .6.5 mmol/L or use of cholesterol-lowering agents). In addition, we assessed whether any differenceswere found in the initial technical success rate or the 3-month clinicalresults (systolic and diastolic blood pressure, number of antihyper-tensive drugs, and serum creatinine level) between the 2 groups.ResultsIVUS images were obtained in 18 patients before interventionand in 18 other patients after predilatation with an angioplastyballoon 5 or 6 mm in diameter. In the remaining 12 patients,the interventionist did not use IVUS before stent placement.Quantitative IVUS data for the group studied beforeintervention are given in the Table. Nine of 18 patientsshowed the coarctation phenomenon, with an MBA at thetarget site of 24.065.1 mm2, which was significantly smallerthan that in the adaptive remodeling group (33.966.8 mm2,P50.003; Figure). PLA in the coarctation group(13.964.4 mm2) was also significantly smaller than in theadaptive remodeling group (23.766.1 mm2; P50.001).Quantitative parameters at the reference site and the degree ofarea stenosis were not significantly different between the 2groups. Similar results were found in the 18 patients studiedafter predilatation (Table).The 2 observers showed good observer agreement with regardto the IVUS measurements, with a high correlation coefficient(r50.98; observer 250.983observer 110.64 mm2) and anoverall coefficient of variation of 10.7%. The conclusions wereconsistent for each observer individually. Multivariate regres-sion analysis did not reveal any angiographic or clinical param-eter predictive for either adaptive remodeling or coarctation; nodifferences were encountered in initial technical success and3-month clinical outcome between the 2 groups.DiscussionThe conventional concept of development and progression ofatherosclerotic RAS is the accumulation of plaque, with orwithout compensatory vessel enlargement (ie, adaptive re-modeling). The current findings suggest an alternative mech-anism of symptomatic RAS, characterized by focal narrowingof the renal artery wall and little plaque (ie, coarctation). Thelatter phenomenon was responsible for symptomatic RAS in50% of patients, a prevalence of coarctation similar to thatpreviously seen in our autopsy study.3 Coarctation could beidentified even after balloon dilatation in 44% of the patients.The present study is the first in which coarctation as a causeof RAS was evidenced clinically. It is noteworthy that 32years ago, McCormack et al10 described a proportion ofhistologic RAS with “arterial spasm fixed by accumulation ofQuantitative Cross-Sectional Intravascular Ultrasound Data ofRenal Arteries Before Intervention (n518) and AfterPredilatation (n518)AdaptiveRemodelingGroupCoarctationGroup PBefore intervention n59 n59TargetMBA, mm2 33.966.8 24.065.1 0.003PLA, mm2 23.766.1 13.964.4 0.001ReferenceMBA, mm2 33.567.6 33.963.8 NSPLA, mm2 7.962.0 7.861.4 NSMBA target/reference, % 103613 71611 ,0.001Area stenosis target/reference, % 61.2619.7 61.4619.3 NSAfter predilatation n510 n58TargetMBA, mm2 43.0612.4 24.1610.6 0.004PLA, mm2 28.2613.0 12.368.0 0.008ReferenceMBA, mm2 33.266.3 35.2617.1 NSPLA, mm2 7.861.9 6.962.8 NSMBA target/reference, % 130631 70610 ,0.001Area stenosis target/reference, % 42.5618.0 52.1617.3 NSRenal arteries are divided into the adaptive remodeling and coarctationgroups according to the relative MBA at the target site (.85% and #85%,respectively). Values are mean6SD and represent the averaged results of the2 independent observers. NS indicates not significant.Leertouwer et al June 15, 1999 2977collagen,” which may reflect the coarctation seen in thepresent study. In our previous autopsy study in which wecombined IVUS with histologic analysis, however, coarcta-tion was not associated with specific histologic characteris-tics. Mintz et al11 described de novo stenotic lesions incoronary arteries that were characterized by inadequate re-modeling and less plaque than expected. One might postulatethat these coronary lesions are similar to the coarctationlesions in renal arteries seen in the present study.The pathogenesis of coarctation RAS obviously remainsspeculative at this stage. Abdominal aortic coarctation, withor without involvement of the renal arteries, may be related torenal artery coarctation but, as with fibromuscular dysplasia,Takayasu’s arteritis, and neurofibromatosis, this is a rela-tively rare cause of RAS that commonly involves youngerpatients. In the present study, angiographic and clinical datawere similar for both the adaptive remodeling and thecoarctation groups. In the coronary artery study of Mintz etal,11 a significant association was found between inadequateremodeling lesions and the extent of lesion calcium. This ledthe authors to postulate that inadequate remodeling was amanifestation of advanced atherosclerosis. In the presentstudy in renal arteries, however, only small, incidental speck-les of calcium were present, both in the adaptive remodelingand the coarctation groups. This, together with the fact thatcoarctation was also evident in human cadaveric renal arterieswithout plaque accumulation, suggests that in renal arteries,coarctation is a non–plaque-determined phenomenon, possi-bly related to an early rather than a late stage of atheroscle-rosis or perhaps not even related to atherosclerosis at all.Clinical ImplicationsThe heterogeneity of atherosclerotic RAS, as shown in thepresent study, may have important clinical implications.Plaque-focused treatment by means of intravascular radiationtherapy or plaque-lowering agents could be of minor impor-tance for coarctation RAS. In addition, renal artery revascu-larization by either balloon angioplasty or stent placement isclinically successful in only part of the patient populationtreated.12 Currently, which parameters determine the outcomeof revascularization is insufficiently known. Whether the typeof RAS determines the outcome of intervention is a questionthat will be investigated in future studies.A limitation of our study was that IVUS images were notobtained in all 48 patients. This may have resulted in aselection bias; the prevalence of coarctation RAS as present-ed here must, therefore, be interpreted with caution.AcknowledgmentsWe thank Johanna L. Bosch, Department of Biostatistics, forperforming the multivariate analysis and Teun Rijsdijk for thephotographic work. This project was supported by grants from theRevolving Fund (1996-26) of the Erasmus University MedicalCenter, Rotterdam, and Cordis (a Johnson & Johnson Company).References1. Holley KE, Hunt JC, Brown AL, Kincaid OW, Sheps SG. Renal arterystenosis: a clinical-pathologic study in normotensive and hypertensivepatients. Am J Med. 1964;37:14–22.2. Schwartz CJ, White TA. Stenosis of the renal artery: an unselectednecropsy study. BMJ. 1964;2:1415–1421.3. Leertouwer TC, Gussenhoven EJ, van Jaarsveld BC, van Overhagen H,Bom N, Man in ‘t Veld AJ. In vitro validation, with histology, ofintravascular ultrasound in renal arteries. J Hypertens. 1999;17:271–277.4. Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, KolettisGJ. Compensatory enlargement of human atherosclerotic coronaryarteries. N Engl J Med. 1987;316:1371–1375.5. Pasterkamp G, Borst C, Post MJ, Mali WP, Wensing PJ, Gussenhoven EJ,Hillen B. Atherosclerotic arterial remodeling in the superficial femoralartery: individual variation in local compensatory enlargement response.Circulation. 1996;93:1818–1825.6. Berglund H, Luo H, Nishioka T, Fishbein MC, Eigler NL, Tabak SW,Siegel RJ. Highly localized arterial remodeling in patients with coronaryatherosclerosis: an intravascular ultrasound study. Circulation. 1997;96:1470–1476.7. Dorland’s Illustrated Medical Dictionary. 28th ed. Philadelphia, Pa: WBSaunders Co; 1994.8. Bom N, ten Hoff H, Lancee CT, Gussenhoven WJ, Bosch JG. Early andrecent intraluminal ultrasound devices. Int J Cardiac Imaging. 1989;4:79–88.9. Kaatee R, Beek FJ, Verschuyl EJ, van de Ven PJ, Beutler JJ, van SchaikJP, Mali WP. Atherosclerotic renal artery stenosis: ostial or truncal?Radiology. 1996;199:637–640.10. McCormack LJ, Poutasse EF, Meaney TF, Noto TJ Jr, Dustan HP. Apathologic-arteriographic correlation of renal arterial disease. Am Heart J.1966;72:188–198.11. Mintz GS, Kent KM, Pichard AD, Satler LF, Popma JJ, Leon MB.Contribution of inadequate arterial remodeling to the development offocal coronary artery stenoses: an intravascular ultrasound study. Circu-lation. 1997;95:1791–1798.12. Blum U, Krumme B, Flugel P, Gabelmann A, Lehnert T, Buitrago-TellezC, Schollmeyer P, Langer M. Treatment of ostial renal-artery stenoseswith vascular endoprostheses after angiographic unsuccessful balloonangioplasty. N Engl J Med. 1997;336:459–465.IVUS cross-sections obtained from renal arteries before inter-vention showing adaptive remodeling (A) and coarctation (B)types of renal artery stenosis. Left panels represent target sites,and right panels indicate reference sites. Cross-sections arecontour-traced, facilitating recognition of LA (inner contour) andMBA (outer contour). Note relatively small media-bounded areaand little plaque seen in coarctation stenosis (B). Calibra-tion51 mm; black circle5catheter.2978 Coarctation Causes Renal Artery Stenosis

Intravascular ultrasound evidence for coarctation causing symptomatic renal artery stenosis

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Intravascular ultrasound evidence for coarctation causing symptomatic renal artery stenosis

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