Combined physiologic and anatomic assessment of percutaneous revascularization using a Doppler guidewire and ultrasound catheter

Combined Physiologic and Anatomic Assessment of Percutaneous Revascularization Using a Doppler Guidewire and Ultrasound Catheter Jeffrey M. Isner, MD, Jenifer Kaufman, BS, Kenneth Rosenfield, MD, Ann Pieczek, Robert Schainfeld, MD, K. Ramaswamy, MD, and Bernard D. Kosowsky, MD

Previous hwestiiions have estaMi the utility of intravascular uttrasound (WDS) examination for the evaluation of arterial dimensions and qualttte changes followJng percutaneous revascularizatiin. More recently, the feasJbJlity of obtaklng intravascular physklogy fhtdlngs before and/or after percutaneous revascularization by use of an intravascular Doppler Flowire (Dardiimetrks) has been demonstrated. Accordhrgly, we hvestiied the feasibilRy of using this combined physioJogk/anatomk approach to evaluate individuals undergohu# percutaneous revascularkation of stenotk or occluded coronary and peripheral arterks. A total of 76 patients were evaluated using the Flowire to guide an IVDS catheter. Revascularkation of coronary and peripheral vascular stenoses and/or occh~sions was achieved in these patients by balloon angioplasty, directional atherectomy, excimer laser angioplasty, and thrombolytk therapy, alone or in combination. Physkkgk findi~ obtained with the Flowire reinforced conclusions regarding morphologic severity of candidate stenoses and anatomk adequacy of revascularization following IVDS examination. In certain ambiguous cases, kformatkn gained by one modality ctarRied information obtaked with the other. Finally, one modality may ako serve as an aRematJJe when logistics preclude the serial use of both. The preliminary experience obtained in this feasfbility trial confirmed that MJS and the Flowhe may be combined to assess both candidate lesions as

From the Departments of Medicine (Cardiology), Biomedical Research, Radiology and Vascular Surgery, St. Elizabeth’s Hospital, Tufts University School of Medicine, Boston, Massachusetts. Supported in part by an Academic Award in Vascular Medicine (HL02824) from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Address for reprints: Jeffrey M. Isner, MD, St. Elizabeth’s Hospital, 736 Cambridge Street, Boston, Massachusetts 02135.

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well as postprocedural patency in patients undergoing percutaneous revascularizatkn. The combination of anatomk and physkkgk data available from MB and Flowtre provides a far more sensitive and possibly more accurate analysis of the adequacy of revascularization than has been possible by angiography alone. l’he extent to which such a detailed investigation is required to optimize interventional therapy on a routine basis is the subject of subsequent investigations. (Am J CardJoJ 1993;7lz7OD-4SD)

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revious investigations have documented the utility of intravascular ultrasound (IVUS) examination for the evaluation of arterial dimensions and qualitative changes following percutaneous revascularization.l-lo Studies performed to date have established the superiority of IVUS examination over quantitative angiography for assessment of these anatomic features.“-l3 Both IVUS and quantitative angiography, however, share in common the liability that each identifies only morphologic alterations; consequently, conclusions regarding the adequacy of revascularization are currently compromised by failure to complement anatomic assessment with physiologic analysis. The feasibility of obtaining intravascular physiologic findings before and/or after percutaneous revascularization by use of an intravascular Doppler wire has been documented recently by several investigators.‘4-2n This guidewire has been described in detail elsewhere in this Supplement. It has two distinct advantages that make it suitable for combined use with IVUS. First, the wire caliber (0.01%in) is easily accommodated by most current IVUS catheters, thus allowing the Doppler wire to serve as a guidewire for both the ultrasound catheter as well as other therapeutic devices. SecMAY 20, 1993

Intravascular

Ultrasound

Image

Spectral Velocity

Display

FlGURE l. Schematk diagram of comblned use of Flowlre and intravascular utrasound (MJS) catheter. Central panel discloses IVUS catheb wlthln the lesion of Interest. Cathebr has been advanced over a Flowlre that proJects distally. Astdsk marks the site of sample volume, 5 mm distal to the &Hal tlp of the wire. A 24 measknalmorphologkImagek recoded from the IVUS catheter. Spectral vekdty display, showing In thls case the pressure contour typkal of a -I peripheral artery (I.e., systolk predominance), ls recorded from the wire. ACC = acceleration; APV = average peak velodty; CPI = Cardkmetrks pulsatllRy Index; D = dlastollc; MPV = maximum peak velocRy; S = systolic.

ond, in contrast to previous Doppler catheters in which flow could only be assessed at the ostium of the artery, i.e., proximal to most stenoses, location of the Doppler transducer crystal at the distal tip of the guidewire allows assessment of flow distal to the obstructing lesion. Thus, the Doppler guidewire establishes the opportunity to perform serial physiologic assessment before as well as after revascularization. Accordingly, we investigated the feasibility of using this combined physiologic/anatomic approach to evaluate individuals undergoing percutaneous revascularization of stenotic or occluded coronary and peripheral arteries. METHODS Intravascular Doppler flow velocity analysis: A 0.01%in Doppler-tipped guidewire (Flowire; Cardiometrics, Mountain View, CA) was placed distal to the target lesion (Figure 1). Among those cases in which the target vessel was totally occluded, the lesion was first crossed with a hydrophilic wire (Glidewire; Terumo, Tokyo; distributor: Medi-Tech, Watertown, MA), following which a 4 F catheter (Royal Flush; Cook, Bloomington, IN) or 5 F, 0.038-in Tracker catheter (SciMed Life Systems, Maple Grove, MN) was used to exchange the Glidewire for the Doppler Flowire. Flow velocity parameters were recorded at baseline and following each successive intervention. In all cases of antegrade, ipsilateral, infrainguinal lower extremity revascularization procedures, hyperemic response was assessed by administration of 300 kg of nitroglycerin through the side arm of the introducer sheath; measurements were recorded at 30,

60, and 90 set after nitroglycerin administration. The Flowire measures 0.5-mm in diameter; the sample volume is therefore obtained at a distance of 10 diameters, or 5 mm, distal to the tip of the wire (Figure 1). The spectral velocity display typical of a normal coronary artery has been described elsewhere.14J5J7-20 The spectral display representing a typical recording obtained from a lower extremity peripheral artery with the Flowire is shown on the right of Figure 1; systolic and diastolic components are marked by the vertical lines corresponding to the electrocardiographic signal. Calculated parameters include the maximum peak velocity (the apex of the systolic deflection in the periphery); and the average peak velocity (the average of both the systolic and diastolic components of 2 cardiac cycles). Intravascular IVUS catheter: The IVUS catheters (Boston Scientific, Watertown, MA) used in the present investigation have been described previously.2A,” Briefly, the 6.0 F catheter consists of a braided polyethlyene outer shell enclosing a rotary driveshaft with a single element transducer at its tip, and measures 95 cm in length. The 3.5 F catheter is nonbraided, multilayered, and acoustically transparent with integral electrical shielding designed to improve signal-to-noise ratio. Both are constructed as a monorail design. A 0.01%in guidewire (Peripheral Systems Group, Mountain View, CA; or Microvena Corp, Vadnais Heights, MN) was used in conjunction with both catheters; this catheter guidewire combination is easily accommodated by a conventional 8 F sheath or guiding catheters with a minimum inner dimension of 0.79 inch. A SYMPOSIUM:

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FlGURE 2. htifact produced by slmuRansous lmaglng with latravascular ultrasound atheter aMacts are swn on laft wtth Flowlra on; artifact dlsappsars whsn Flowlre Is tumad off.

For both catheters, nominal transducer center frequency is 20 MHz with a fractional bandwidth of > 45%. Ultrasound transmission occurs at < 7 dB attenuation with the 6.0 F catheter, and <3 dB with the 3.5 F device. The transducer aperture of the 6 F is 1 mm laterally and is lens-focused to an average distance of 2 mm. The 3.5 F catheter incorporates a 0.66 mm circular aperture. Typical depth of field is 0.7-4.5 mm for the 6.0 F device and < 1.5 mm for the 3.5 F. Lateral resolution for both catheters is approximately 0.1 mm and axial resolution is approximately 0.05 mm. Significant beam spreading develops beyond 5 mm axial distance for the 6.0 F device, and > 15 mm for the 3.5 F version. Both catheters are used with an imaging console adapted for 20 MHz operation and 360” scans (Hewlett-Packard, Andover, MA), at 30 scans/set, corresponding to 1,800 rpm. Vectors are converted, stored, processed, and displayed through a state-of-the-art high-speed digital scan converter with standard video output, allowing images to be archived on videotape or a multiformat film camera for later study. A videotape hardcopy unit is also available for recording still images during the procedure. Technical Issues related specIkally to comMned MJS and FloMap imagi~@ Use of the Doppler wire as the guidewire for the IVUS catheter implies that the Flowire recording will always be obtained distal to the site being inspected by IVUS; this is because the crystal for Doppler recording is mounted at the distal tip of the wire, whereas the ultrasound transducer is positioned approximately 2 cm proximal to the 72D

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and Flowlra. Radial llnsar

distal tip of the ultrasound catheter. Further, the sample volume recorded from the wire corresponds to a site 10 diameters (total 5 mm) distal to the tip of the Doppler wire. As a result, simultaneous recording of both ultrasound and Flowire would require that the ultrasound transducer actually be placed distal to the tip of the Flowire. To circumvent this limitation, we have, in nearly all cases, positioned the tip of the Flowire several centimeters beyond the most distal obstruction so that the recorded flow signal reflects the degree of obstruction imposed by the stenotic lesion; we have then attempted to image those lesions in a serial rather than simultaneous fashion using IVUS examination. Simultaneous use of both devices also creates the potential for cross-talk between the IVUS and Flowire signals. Recording from both the IVUS and Flowire simultaneously, the IVUS images are distorted by artifact resulting from the Doppler instrumentation (Figure 2). As shown in the ultrasound image recorded with the Flowire disconnected, the artifact disappears immediately. Finally, simultaneous imaging also leads to the potential for the bulk of the ultrasound catheter itself to obstruct flow in a high-grade stenosis and thereby further compromise the recorded flow velocity signal. A recognizable flow signal is recorded with the ultrasound catheter placed proximal to the site of maximum obstruction (Figure 3). As the ultrasound catheter is advanced into the stenotic lesion, however, a marked reduction in flow velocity signal occurs, presumably related to obstruction of the residual lumen by the 6 F MAY 20,

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ultrasound catheter (Figure 3). To obviate this potential, the flow velocity signal was recorded, when possible, with the wire placed distal to the lesion and no catheter within the introducer sheath in the case of a peripheral artery or within the guiding catheter in the case of a coronary artery. Revascularfzation: A total of 76 patients were evaluated using the Flowire to guide an IVUS catheter. Revascularization of coronary and peripheral vascular stenoses and/or occlusions was achieved in these patients by balloon angioplasty, directional atherectomy, excimer laser angioplasty, and thrombolytic therapy alone or in combination. RESULTS Representative cases: The following cases have been selected to illustrate the combined use of the Flowire and IVUS analysis in coronary and peripheral arterial revascularization. hthti:EVALUATIONOFCORONARYRESTENOSIS BEFORE LASER ANGIOPLASTY: This patient

had undergone percutaneous transluminal coronary angioplasty (PTCA) 3 times previously for recurrent stenosis in the left anterior descending coronary artery (Figure 4). Prior to further treatment, she was referred for evaluation regarding the possibility that restenosis on this occasion involved the origin of the left diagonal branch as well as the left anterior descending artery itself. Sequential IVUS and Flowire analyses were therefore performed of the left diagonal lesion and the left anterior descending artery. Following determination that the lesion involved the left anterior descending artery but not the left diagonal, excimer laser angioplasty (Spectranetics, Colorado Springs, CO) followed by PTCA was performed for the left anterior descending lesion. The initial IVUS examination of the left anterior descending artery prior to PTCA (Figure 5) shows the IVUS catheter positioned within a highgrade obstruction in the proximal left anterior descending artery. The accompanying 3-dimensional reconstruction (sagittal view) discloses a relatively tubular segment in which the fibrotic plaque encroaches on the IVUS catheter; the arrows point out the origin of the left diagonal branch. The 3-dimensional reconstruction (sagittal view; Figure 5, top right) of the left anterior descending artery at the origin of the left diagonal branch documents the absence of any obstructive lesion at the origin of the left diagonal. The coronary velocity recordings (Figure 5, lower panels) obtained from the left anterior descending (left) and the left diagonal (right) branches show an abnormal flow pattern in

the left anterior descending artery with a borderline diastolic/systolic velocity ratio (DSVR) of 1.4, indicating only modest diastolic predominance. In contrast, the flow velocity signal recorded from the left diagonal discloses marked diastolic predominance (DSVR = 2.4). Following excimer laser angioplasty (Figure 6), improved luminal patency in both the 2-dimensional and 3-dimensional reconstructions of the left anterior descending artery can be appreciated. The corresponding flow velocity now demonstrates a marked improvement in DSVR (2.1) with obvious diastolic predominance. PathIt 2: EVALUATION OF COMPLICATIONS OF CORONARY ANGIOPLASTY: In a patient with recent myocardial infarction, a high-grade stenosis of the right coronary artery (Figure 7) was initially dilated with a 3.0-mm balloon catheter (Slider; Mansfield Scientific, Watertown, MA) over a 0.014-in wire through a 0.079-in guiding catheter (JR4; Schneider, Plymouth, MA). The improved luminal diameter

FWURE 3. Effect of Intravascular uRrasound (MJS) catheter placed wtthln lesion on flow velocRy rewrded distally before revasculaftzatlon. Upperpanel: typkal phask Row velocRy-nglsobtalnedtromtheFlowlNwhenlvuS catheter Is proximal to the SRe ofobstrwtlon SlKwlng wldelypatenltlumen(L).Lowerpiwel:flowlreremalnrrat the ldentkal locatlon, distal to the pfopased sRe of revascularlzatlon. Flaw Is now obstwhd, however, byenby@f the IVUS catheter Into the sRe of cross-Wnal area 0ntbeMJSIm narrowing. No lumen can be appfwlated age. Comspondl~, there Is a marked re4ductlon In Row velocRyrewwkd.Arrowslnboththeunob&uctedand obdrwtd flow bnages lndkate artifact produced by slmultaneous l,pwglngwlth MS cathetwandFlowlre. A SYMPOSIUM:

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730

FlGltRE4.useofiubasound(MJS)andFlowlreto deflneextentofstenosklnthe proximal left antalar M artwy (UD) and potentM InvolvennMtofleRdlagonal(LD) branchatthedteoflADstene slsha,Bse5nean@ngramrs --fo-w63P-k-PercutaneoustraMllmlnalcoroMmy m!W-W(PTCA)~~a lesbnInvolvlngthep8oxlmalLAD, LDbshownaWlngfbomtheMD. (Lc=lettclrcumRe~LM=left nlaln.) b, lvus cathetwandFlowlreposWnedInLDprlortorevasculallzatkn.c,rwsandFlowlrereposltloneulInLAD pllor to revascubrbatlon. d, Anglogram mcordedtdlowhg evaluatlonbylWSandFlowlreand aeatlllMtOflAD-by~X-

clmerlaserandbalkonangb Plarty.

RGURE 5. Upperpanek: intravascular uRrasound (MJS) and Flowlre recordl~~! obtalned In patlent showm In Figure 4, prior to revascularlzatlon. IVUS Image of left anterior descendlng(UD)beforepercutaneoustranslumkralcoroMy an&bpbty(fTCA)dkcloseshlglwgradeobstnAon In the 2Ilmenslonal view. ConerpOnang saglttal reconrtrudlan of IAD shows plaque abutting catheter at the site of tubular steno&s (arrows). Threwllnw l&OMlS@tW-ot the left diagonal (LD) branch otlgln from the LAD (LAD Dl) show no l&ement of flrst diagonal branch @I). Lowwpane/s: Flow velocity recordings shobm below show suboptlmal dlastolk predomlnfmce of Row In the LAD. In contra&, them ls marked dlastolk predominance In the LD. APV = average peakvekdty; DSVR = d --l-W-. 740 THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 71 MAY 20, 1993

was compromised by substantial recoil restenosis. A second inflation at the same inflation pressure (8 atm) resulted in a small dissection. After 5 minutes, the angiographic appearance of the PTCA site was not improved. To evaluate the lesion and because the PTCA balloon would not accept the 0.018-in wire, the Flowire was advanced through the guiding catheter and down the right coronary artery alongside the initially positioned 0.014-in wire. The latter was then removed and baseline right coronary artery flow velocities were measured, indicating a baseline DSVR of 1:l. Moreover, the average peak velocity appeared to be reduced and it was therefore decided to perform an additional inflation. The PTCAcatheter (3.0-mm balloon) was then advanced to the site of the lesion and an additional dilation was performed, and after removing the balloon, a 3.5 F IVUS catheter was advanced over the Flowire to perform ultrasound examination of the dilated site. A nearly circumferential dissection of the right coronary artery at the PTCA site was seen; a pullback recording was then performed for 3-dimensional reconstruction. A repeat measurement of flow velocity disclosed no change in flow velocity. The abnormal DSVR ratio and the ultrasound appearance of a severe circumferential dissection suggested that the angioplasty result could not be considered final. It was therefore decided to use a 3.0-mm Stack perfusion balloon catheter (ACS, Santa Clara, CA) to perform a long inflation. Because of equipment and guiding catheter dimensions, the perfusion catheter could not be advanced. Therefore, after advancing the 0.014-in exchange wire distal to the lesion, the 0.018-in Flowire was removed. The perfusion balloon catheter was then advanced to the PTCA site and a 15minute inflation performed, which was not well tolerated. By exchanging the 0.014-in for the 0.018-in wire (advanced through the perfusion balloon lumen), severely compromised flow was noted (Figure 8). After deflating the balloon and immediately removing the perfusion balloon catheter, there was a prompt increase in flow, although the DSVR remained approximately 1.2. An angiogram recorded following removal of the perfusion balloon catheter documented a satisfactory result. This case illustrates several important points. First, for combined use of IVUS and Flowire examination within the coronary arteries, the size of the guiding catheter must be able to accommodate the multiple instrumentation required. Second, the lumen of the perfusion balloon catheter should not be obstructed by guidewires during balloon dilation, as demonstrated by intracatheter

flow velocity measurements. Third, relatively modest changes can be frequently observed in the DSVR, even when the angiographic result is acceptable. It is noteworthy that during the final pullback recording obtained with the Flowire, no velocity gradient could be demonstrated for the DSVR between the site distal to the initial PTCA site and the proximal portion of the vessel. Finally, IVUS examination was not performed at the completion of the procedure due to the concern that a metastable lesion could be compromised by further instrumentation. Thus, coronary ultrasound proved useful for documenting the severity of the initial dissection, but the potentially less traumatic Flowire was used to perform serial investigations regarding the adequacy of the intervention. Patient ~:RENALOSTIALLESIONS: Thediagnostic angiogram of a patient with an ostial lesion in the right renal artery was recorded with a 0.082-in guiding catheter (Superflow RES; Schneider; Figure 9). The Flowire was passed into the right renal artery over which a 3.5 F IVUS catheter was

FlGURE 6. Intravascular utresound (MJ5) and Flowlre cecordlngsobtalnedefterexdmerleserandp~ traneluminel coronary angleplasty (PTCA) In the petlent deembed In Figures 4 and 5. Roth 2-dlmenslonel and 3-dlmenalonal IVUS Imeges recorded after revascularlzatlon show marked lmprevement In lumlnal patency. Cowespndlng FloMap recording now shows restoretlen of unequivocal dlestollc predominance of flow. For other abbrevlatlons, see Figure 5. A SYMPOSIUM: DOPPLER FLOW VELOCITY 75D

FlGURE 7. Use of Wravasubr uRrasound (IVUS) and Flowlre In a patkntwRhawtedss8cUonafter percutaneous translumlnal coronary amlasty (PICA). A, Pre-PTCAa~mshowshlghgradestewslsIndlstalrightcoronary artery (RCA). 6, FolkwIng lntlal balloon lnflaUon, there is an acute dlssectb. C, FdU addRknalballoonlnRauons,the dbsectlon persists, and there Is residual lumlnal narrowh& D, MIS transducer ls advanced over theFlawlretolnspectPlCAsRe and measure RowvehxRy. E, Perfusion balloon cathebr (PBCIP sltkmedatPlAsltewRhFlowlre InthlscasepesRbnedthroq@ the4 lumen of the PRC. F. Final an-

iliac arteries were totally occluded from the origin at the aorta to the common femoral artery. The aorta itself had a stenosis in its distal, infrarenal segment, and the left common iliac artery was stenotic as well. Because the patient was judged to be a poor candidate for bypass surgery, it was elected to dilate and stent the abdominal aorta and/or left external iliac artery prior to performing a cross-femoral graft from the left common femoral artery to the right common femoral artery. A 3-dimensional reconstruction of the ultrasound images obtained during a pullback from the suprarenal (proximal) aorta, through the stenotic segment and finally through the distal, poststenotic segment, is shown on Figure 10. Representative 2-dimensional ultrasound images are illustrated on the left, and representative Flowire recordings are illustrated on the right. Notice the gradient in flow velocity recorded from the proximal versus the distal aortic segments and the peak flow velocity htht 4: STENT PLACEMENT IN PERIPHERAL recorded in the vortex shed of the stenosis. VASCULAR DISEASE: This 57-year-old woman had a Following these initial recordings, an 8 mm x 3 history of coronary artery disease and underwent cm percutaneous transluminal angioplasty (PTA) coronary artery bypass surgery 6 years before balloon catheter (USCI, Billerica, MA) with a presenting with symptoms of right lower extremity premounted Palmaz stent was advanced over the claudication. Diagnostic angiography (Figures 10, guidewire and positioned using angiographic and 11) disclosed that the right common and external predetermined ultrasound measurements to guide

advanced. The arterial lumen is totally obstructed by atherosclerotic plaque (Figure 9, middle panel), leaving a residual lumen barely large enough to accommodate the IVUS transducer. The corresponding flow velocity signal (Figure 9, lower left) indicates an average peak velocity of 40 cm/set. Note also the delayed acceleration in the upstroke of the flow velocity signal. Following angioplasty, a 5 x 18 mm PalmazSchatz stent (Johnson & Johnson Interventional Systems, Warren, NJ) was delivered to the right renal ostium. The angiographic improvement in luminal patency (Figure 9, top right) is corroborated by the IWS image immediately below, which demonstrates full expansion of the individual struts of the stent. The flow velocity signal after stent placement confirms the improved result: the average peak velocity has increased by 50% to 60 cm/set with a nearly vertical acceleration in the upstroke of the flow velocity signal.

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RGURE 8. Fiowire and intravascular utrasound (MJS) findings recorded in patient whose angio@ams were shown in Fi@~re 7. Top left panel illustrates flow veiocRy recorded wlth the wlre piaced through the lumen of the inflated perfuskn balloon catheter (PRC). Top middle pane/ displays augmentation in flow veiocity immediateiy foilowing defiatkn and wtthdrawai of P8C. Rottom 3 left pane/s d emonst&e Fiowire recordings made distal to, at, and proximal to the PTCA site. Note that in contra4 to recordings shown above, a biphasic (systoik-to-diastoik) flow contour has been restored. in addition, there is no gradient from proxhnai to distal and oniy a small augmentaWm of fiowveiocity at the vortex shed (PTCA sRe). URrasound recordings at tight demonstrate representatlve 2dimensionai and 34bnensionai reconstructions obtained after PTCA, but prior to PSC. The 2dimensionai views dearly show a nearly cir wmfemntiai dissection of right coronary artery. 8agittai views beiow in 2 diRerent proJections show that the circumferentiai dissection results in persistent iuminai cross-sectional area narrowing. MPV = maximum peak veiodty. For other abbreviations, see Figure 5.

FlGuRE9.AngkbgmplIkultrasoundandFkwCewaflamnmt.m t=kFad-anglogramrecoded befomthb -ntplecement-m gradeostlalleaknllntlle~ renal artery. @iwqwWg ultrs SOUlldhUlgtBWOfdBdb&W ShOVB~COflpkt@UOSS.

sectkmafareanarrowhgby plaqueabutthgthe Intmwsadar u-(MJs)tran8ducer. Basellnetknvvelodtyls4oan/ sec.Thaa~atterstent

p-rhonnmarkecilm : provement In lumhai patency at theostkimoftheri@tre4dartey,---lS

presentatthlsstte.MJs-

In& In contrast, shows u-allfted, marked Improvement ln lumlnal cress-sectknal area. --m&nnlmst~lmp~einenth maximum peak vdctty to nearty socnl/sec.

,its placement. The stem was deployed at an inflation pressure of 10 atm. Following deployment of the stent, pressure gradients were measured across the stent and disclosed a reverse gradient (176/63 mm Hg proximal to the stent vs 185/67 mm Hg distal to the stent). The 3-dimensional reconstruction of the abdominal aorta obtained poststent deployment (Figure 11) shows a uniform luminal diameter, which is confirmed by 2-dimensional IVUS images proximal to, at the site of, and distal to the stent. The stent struts are well seen in the middle panel. Corresponding flow velocity signals obtained proximal to, within, and distal to the stent are compared with recordings obtained before stent deployment showing a uniform flow velocity throughout the distal abdominal aorta, with loss of the peak flow velocity previously recorded at the vortex shed of the aortic stenosis. Serial interventions in peripheral vascular disease: Patient 5: The baseline angiogram (Fig78D

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ure 12) shows a series of stenotic lesions in ?fte superficial femoral artery. Peripheral PTA with a 5mm balloon catheter was angiographically successful. The maximal peak flow velocity recorded following 5mm balloon inflation was 81 cm/set, which augments to only 108 cm/set follovving intra-arterial nitroglycerin. Close inspection by IVUS, however, reveals 2 residual sites of narrowing in the superficial femoral artery. Accordingly, PTA was repeated with a 6-mm balloon catheter (Ultrathin; MediTech). The angiogram (Figure 13), once again, appeared satisfactory. The flow velocity recording was repeated and showed improvement to 116 cm/set, with substantial augmentation following intra-arterial nitroglycerin. Inspection by IVUS disclosed no residual narrowing at the sites previously determined to represent residual stenoses following 5-mm PTA. Only subtle differences of the angiographic findings were noted following 5-mm PTA comMAY 20,

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FIWNE la lnbavaocular ultrasound (MIS) and Flowlre flndlngs before percutaneous tranoluminal angloplasty and stent trestmewtofstenotkleslonlnthedlstal abdominal aorta. Three-l-CtlOllof the distal abdominal aorta lo shown In the lumlnal cast format lnfli6centewoftheflgure.CorresPonmi!ulmag- WV and Fkwim recardngs (ffght) obtalned proximal to, at, and distal toslteof stenos&. Note crosssectlonal area narrowlngshown atslteofsteno& In the IVUS lm~J#B. Note that the FlowIre recordlngsdenmstdeagradlentfrom proximal to dlstal sttes In flow vdoolty, and a marked Increase Mffbwvelo&yatthevortex shed, or stenosis.

pared to those obtained following 6-mm PTA. In this particular patient, the ultrasound and Doppler flow proved more sensitive for documenting the optimal result achieved following the final 6-mm PTA. Patient 6: The diagnostic angiogram (Figure 14) indicates an occlusive lesion in the area of the

adductor canal with distal reconstruction via collaterals. After difficulty was encountered during attempts to advance an angled Glidewire through the occlusion, a 0.035-in straight Glidewire was used to cross the occlusion without difficulty. This wire was then exchanged for a 4 F straight catheter, which was used to document the intravascular position of

FIGUREii. Intravascular ultrasound (MIS) and Flowlreflndlngs apgrstenttherapyofpatlMt shownlnFlgwel9.Lumlnalcast 34mnhnalreconstructlonln thecenteroftheflgure.howsthe hprlnt ofthe Palmaz-&hat2 stentattheslteoforlglnalstenosls.MlSlmagesonleftshowno resldualobstnstlon.Flowlrerecordqp5on&#tshownovarlathn In flow veloctty from proximal to dbbtal sites, lncludlng at the slteoforlglnalstelwls.

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Pnst-Fimm

PTA

FIGURE l2. Top left: besellne an. glogram of the supeMclal femoralartefybeforem translumhml angkplasty (prePTA). Anglogram In the middle top penddlsclosesareesowUysatlshctoq result folknulng 8-mn Pl~butlnbavascularultrasound (MIS; top night) dkcloees 2 sites with high-grade resklual crosssectlonel area namwlng(asterlsk ldentmes MIS tram). BOttOlHkttpIdShOWSthHitOW

vekdty recorded after &mm PTA Is 81 cm/se<: and augments to 108 cm/set following Intrawterlal nltroglycerln (bottom ffght). Notke that major a@meMaWn after nltroglycerln Involves d&stolk, rather than systolk, flow vekwlty.

Post-6mm

PTA

FlGuREl2.Anglographkhltravascular uttrasound (MJS) and Dopplerflndhgsreawdedfol~ b8g &mm percuteneous translumlnal angk@as@ (PTA) of patket Illustrated In Figure l2. Aq#loglXUllSNMXWdEd~8-tiVW-

susefterWnmPlAaredHfkutt to dlstlngulsh (top kit). lvu8 analyskoftheresuttobtalned after &mm PT& however, now hldkateebnprovedctlonalareanarrowlngatsltw thetwerepwlouslydetemllned to be narmwed (top rqght). comespondlll%)y,therek~rtherlln. provement In maxbnum peak velodty(MPv)toll6cm/secwlth restoretlonofatrlphaekfBow pettern (bottom feR). Follow& Intra-arteHal nttroglycerln, there lsaugnw&Wmot’bothsystolk anddlastolkflowveloclty(be/ow WN.

the wire and catheter. A 4 F catheter was used to advance the Flowire into the tibioperoneal trunk and baseline flow velocity recorded. A 2.2-mm excimer laser catheter (Spectranetics, Colorado Springs, CO) was then advanced over the Doppler wire throughout the length of the total occlusion. Several passes with energy increasing from 50 to 60 mJ/mm2 were made. Progressive improvement in luminal patency for each laser attempt was suggested by serial angiograms. The corresponding flow velocity recordings, however, revealed little change in distal flow velocity following completion of laser angioplasty, possibly due to persistence of a significant residual stenosis. Therefore, adjunctive balloon angioplasty was performed using a 6 MediTech). mm x 10 cm PTA catheter (Ultrathin; The combined physiologic and anatomic findings obtained after PTA demonstrated a dramatic increase in resting flow velocity and a marked improvement in luminal caliber documented by IVUS.

Although there was clear-cut angiographic improvement after the completion of laser angioplasty, resultant analysis by angiography was insufficient to document a significant increase in flow. Ultrasound confirmed that this failure was the result of a residual high-grade stenosis in the superficial femoral artery. Patient 7: The baseline angiogram (Figure 1.5, top left) shows a series of high-grade tubular restenosis lesions in a patient who had previously undergone successful revascularization of an occluded superficial femoral artery. Prior to excimer laser angioplasty, flow velocity was recorded (Figure 15, lower panel). The angiogram following recanalization with a 2.5mm excimer laser catheter (Multiplex; Spectranetics; 50-60 mJ/mm*) over the Doppler wire was marginally acceptable with a significant improvement in maximum peak velocity. Finally, the residual stenosis was treated PTA catheter with a 6 mm x 10 cm Ultrathin

FlGURE U. Angkgraphk, Intravascular uttrasound (lVUS), and Doppler flmllngs In a patlent treated wlth l.7.mm exclmw laser catheter. Baseline angkqgram at top let2 showstotal occluskm (TO) of the superflclal femoral artery proximal to the adductor canal, wlth dktal reconMtutlon In the popllteal atiery bnmedlately above the knee Jolnt. Middle panel shows anglogram recorded foIlowl% exclmer laser revascularlxatlon. Final anglogram, top ffght, shows the resutts recorded after percutaneous trandumlnal angkwlasty (PTA). Flow velocity recordings shown In the bottom panel demonstrate no Improvement In flowvekwity after laser treatment, but marked Improvement after PTA. Correspom#ng MIS Images demonstrate high-grade resklual cross-sectional area narrowing after laser treatment, wlth Improvement after PTA. A SYMPOSIUM:

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FlGURE lS.Aqjlo@apldc, uRrasound,andDopplerflndn@rs cordedfolknvtngexcbnerlaser angkplastyofsuperfkhlhnoral artery (SFA)/poplReal leskms usIng a 2.&mm Mutlplex exclmer lasercathetw.Reforelasewa~ fwW&--@ 2 SRes of --@In the distal SFA and proximal popllteal arteries. ARer laser revascw larlzath,therelsmarkedlnlprovement In km&al patency at both sites. Folkwlng adJunctlve balloonan&@asty,t lstuthe4r Improvement In lumlnal patency. Inset shows lleawscular ulmsound Image reuuded at slteofmaxlmalresklualcrosssectlonal area narrowlng after laserandpercutaneoustranslumlnal an@opbty (PTA), which demonstratesonly2s%crosc sectional area nawowlngby rs sklual plaque (P). Sedal recordIngsofflowvelocRydumonstrate au@nmWth In flow velocRy from baseline to laser revascularlxatlon (maximum peakvelocRy lncreawe IVom 20 to 42 cm/se@. Followl~PTA, there lsfwther Improvement In maximum peak vekclty to 70 cmlsec and rest+ ratkInottrlphadcflowpattefll. D=dlastdlc;S=systolk.

inflated to 12 atm for 1 minute. The final angiogram and ultrasound images (Figure 15, top right panel) documented the satisfactory result, confirmed by the flow velocity recording (Figure 15) of further augmentation of maximum peak velocity and, in addition, restoration of a triphasic flow signal. Thus, in this case the use of a large (2.5 mm) excimer laser catheter allowed significant improvement in luminal caliber with excimer laser alone; nevertheless, the flow velocity recording obtained after excimer laser angioplasty disclosed that the angiographically ambiguous result obtained was still suboptimal and further adjunctive angioplasty was required. 8: CLARIFYING AMBIGUOUS ANGIOPatient GRAM: A 66-year-old man with right lower extremity claudication had a tubular stenosis at the origin of the anterior tibia1 artery (Figure 16). Following PTA with a 3.0 mm x 4 cm PTA catheter (Sub-4; MediTech), a satisfactory flow velocity recording was obtained distal to the anterior tibia1 stenosis. The angiogram in the anteroposterior projection, however, suggested a high-grade residual lesion. IVUS examination (3.5 F catheter advanced over the Flowire) disclosed a residual eccentric, but hemodynamically insignificant, narrowing of the anterior tibia1 artery. The left anterior oblique 82D

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position angiogram confirmed the findings demonstrated by IVUS flow velocity, namely, an eccentric, but nonflow-limiting residual lesion in the anterior tibia1 artery. In this case, the findings obtained by intravascular Doppler and ultrasound analyses suggested a favorable outcome despite ambiguity raised by the nondiagnostic angiographic findings. Patient ~:DISCORDANTULTRASOUND/FL~~IRE FINDINGS: IVUS may be used to identify the basis for failure of flow velocity to improve following an otherwise apparently successful revascularization. A patient with a total occlusion of the superficial femoral artery associated with an ankle-brachial index of 0.55 underwent excimer laser/PTA with an angiographically satisfactory result (Figure 17). An improved ankle-brachial index of 0.85 and elimination of claudication was noted. The flow velocity recorded after excimer laser/PTA failed, however, to show the expected improvement, with a maximum peak velocity of < 30 cm/set. The basis for this failure, illustrated in the bottom left hand panel (Figure 17) is that the 8 F introducer sheath used to advance the wire, laser, and PTA catheter can barely be accommodated by the diminutive common femoral artery in this patient. Specifically, the ratio between the diameter of the sheath and artery is > 0.78 inch, a finding that has been shown MAY 20, 1993

to compromise signal.‘”

distal recording

of flow velocity

DISCUSSION Multiple previous reports12,21-23 have documented the liabilities of angiography, including quantitative angiography,24 in the assessment of luminal diameter narrowing. These various limitations inherent in diagnostic angiography are further compounded when the subject artery involves a previously narrowed site treated by balloon angioplasty or alternative revascularization techniques. In the latter circumstance, the irregular geometry of the fractured and/or dissected sites typical of balloon angioplasty4 and related techniques2 defy accurate analysis, even by quantitative angiography; algorithms developed for calculating luminal cross-sectional area from measurements of angiographic luminal diameter cannot be applied to these unpredictable luminal morphologies. Consequently, angiography may either overestimate or underestimate true cross-sectional area after revascularization.12 IVUS has been shown by several laboratories to solve many of the liabilities associated with diagnostic angiography. l- 1o,25,26 In particular, luminal crosssectional area may be measured directly, regardless of the geometry of the neolumen after revascularization. Calibration issues relevant to quantitative angiography are irrelevant to IVUS because the calibration device (ultrasound catheter) is always immediately within the plane of inspection. Qualitative analysis of the pathologic consequences of balloon angioplasty and related techniques are graphically illustrated. IVUS, however, continues to share an important liability of contrast angiography: acquired information pertains only to morphology; the extent to which such morphologic observations connote physiologic dysfunction must be surmised.12 Preliminary experience with intravascular flow analysis using a Doppler guidewire14-20 suggested to us that this technique could be really married to IVUS. Fortuitously, both the peripheral arterial (6.0 F) and coronary arterial (3.5 F) IVUS catheters employed in our laboratory (Boston Scientific) were designed to accommodate guidewires up to 0.018 inch in diameter. It was therefore apparent that the Doppler Flowire could, while serving as the guidewire or rail for the IVUS catheter, provide physiologic data that would serve to complement the anatomic findings recorded during IVUS examination. The preliminary experience outlined in this

Post-

PTA

FIGURE l.6. Aq&lgraphk, hltmvascular ultrasound (MJS), and Doppler flndlngs after revasculadzatlon of Infrapopllteal leskm. After percutaneous translumlnal angloplasty recoded In the anteropostedr (AP) proWV, miW#mhomogeneous hazinees at PTA site (arlectkndrow) In the ante&w tblal (AT) artery. In the left ante&u ohlhue (LAO) proJection, there Is a dense dye column that Is eccebkdly dlspiacd at the PTA stte, su&jestlng that thehazlnessse4enIntheAPproJectkmlstheresultofrs *al eccenbk plaque (arrow) with a reasona MepodPTA lumen. A 3-dlmenskmal rwonstructlon recaded fi-om

cra§lonal area post-PTAwlth resklual e¢& plaque(P). com?spodngflfowvelocltyshorm belowls codsbntwtthprevlousresults,~demwHdlqjthata satkfadoty peripheral vascular lntewentkm typkally Im provesthemaxhnumpeakvdclty(MPV)to >38cm/sec. For other abbrevlatkms, se+@Figure 1

feasibility trial has confirmed that IVUS and the Flowire may be combined to assess both candidate lesions as well as post-procedural patency in patients undergoing percutaneous revascularization. The extent to which such detailed investigation is required to optimize interventional therapy on a routine basis27 is subject to subsequent investigations. There is no question, however, that the combination of physiologic and anatomic data A SYMPOSIUM:

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Fl8uRE 17. A@q#aphk, haavascular ultrm (MJ8), and

am (WA) ma Bmp pumpeddyelaserwlthabalL t1ppedtiberoptk (c--h Wayland, MA). Before revsrcubrlZdlOll,the8FAkOCdUdOdtor aiwoxh=teb6-;~ lnpl ankbbmM& Index (A6l) ls 0.86. Anor rovascu-, the anglagramdlscbesa~ toryrofudtandthoA8lhaslncroasodto0.66.LomwleRahowa thoMl8tranrduccw(astorkk) uMhlnthe+ktroduwshuathIn tho common feuwwal arteny (CFA); notothatthosheathnealiyoo cludos the CFA. B, @wy~Jiw@wh~baswktedwlthan lncntareIntheA8l,theflcwvs lOClQSlgMl~-dlrtaltO the lnltlal kslon remains low. PTA = porcutanaoustmnskndnal m!W-W

available from IVUS and the Flowire provides a far more sensitive and possibly accurate analysis of the adequacy of revascularization than has been previously achieved by angiography alone. CLINICAL APPUCATIONS Several of the representative cases cited above illustrate the manner in which physiologic findings obtained with the Flowire reinforce conclusions regarding severity of candidate stenoses (Patients 1 and 2) and adequacy of revascularization (Patients 1, 5, 7, and 8) following IVUS examination. It is worth noting, however, that, in certain cases, information gained by one modality may clarify information obtained with the other. In Patient 9, for example, an apparently satisfactory result had been obtained but flow velocity failed to improve. IVUS examination documented an excellent result at the interventional site, and clarified that the failure of the flow velocity signal to increase was related to a mismatch between the diameter of the introducer sheath and the common femoral artery. An analogous phenomenon has been observed 84D

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involving the coronary arteries when the guiding catheter approximates the dimensions of the coronary ostia. One modality may also serve as an alternative when logistics preclude the serial use of both. In the event that IVUS and the Flowire examinations indicate that further revascularization is required for an apparently unstable lesion (as in Patient 2) one may be hesitant to bring the IVUS catheter into the lesion site again, for fear of disrupting the result; in this case, serial recordings from the Doppler wire may still be obtained to confirm the angiographic findings. Likewise, in patients receiving thrombolytic therapy as an adjunct to mechanical revascularization, placement of the Doppler wire may allow one to monitor the onset of reperfusion28 and reserve the use of the IVUS catheter for postmechanical revascularization. The reverse may apply in certain cases involving distal lesions, in which the combination of a taperingvessel and side branches may preclude positioning the Flowire to record a reliable signal; for these situations, it may be possible to advance the 3.5 F MAY 20,

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IVUS catheter far enough distally to inspect the interventional site. Finally, with regard to their complementary or alternative uses, it must be acknowledged that the results of either IVUS or the Flowire may, like any diagnostic techniques, at times be ambiguous. In these cases, the alternative technique may be used to resolve the ambiguity. Combined limitations of modalities From a technical standpoint, several issues merit brief comment. First, as illustrated in Figures 2 and 3, cross-talk may develop between the 2 instruments, creating artifacts in the IVUS image and background “snow” in the Flowire recording; occasionally, these dual distortions require that 1 instrument be turned off and recordings made in a serial fashion. Second, it must be emphasized that flow velocity and anatomy are not recorded simultaneously from the same site. This is due to 2 factors: (a) the site of the sample volume will be at a distance equivalent to 5 wire-diameters (5 mm) distal to the tip of the Flowire being used to guide the IVUS catheter, and (b) the recording crystal of the ultrasound transducer is positioned several millimeters proximal to the end of the monorail IVUS catheter. Further, as was illustrated in Figure 3, even the diminutive bulk of the IVUS catheter can at times compromise flow through a high-grade stenosis. To obviate these problems, we therefore routinely employed the IVUS catheter and Flowire in serial fashion. Further, we typically positioned the Flowire several centimeters distal to the target lesion so that the IVUS catheter could be advanced to the target lesion and still remain on the wire. In both the coronary and peripheral cases, a landmark (a branch in the case of the coronary; a radiographic ruler in the periphery) was identified to guarantee a consistent recording position for the distal tip of the Flowire. A third technical issue implicit in the combined use of IVUS and the Flowire involves the exchange capabilities of the Flowire. For most peripheral cases, the length of the Flowire permits it to be used not only to exchange monorail-designed catheters such as the IVUS catheter described here, but also nonmonorail PTA catheters. The length of the Flowire is insufficient, however, to permit exchange of either nonmonorail PTCA catheters or most nonballoon catheters (e.g., laser, atherectomy) used for coronary and peripheral applications. In such cases, one can attempt to attach an extension wire, although in our experience most extension wire lumens will not routinely accommo-

date the connectorized end of the Flowire. The alternative, illustrated in Patient 2, is to use a balloon-tipped exchange (Trapper) catheter. Finally, for those applications involving large arteries (aorta, iliacs, superficial femoral/popliteal), the distal tip of the Flowire must be protected from bending or inadvertently forming a curve. Although this appears to be less problematic in the case of medium-to-smaller sized arteries such as the coronary or infrapopliteal arteries, such distal curves in larger caliber vessels compromise recording of the Doppler signal. Thus, we have most often used an exchange catheter of some type (Target Therapeutics Tracker, Cook Royal Flush, USC1 Probing Sheath) to introduce the Flowire. Moreover, once in place, care must be taken to avoid irregularities on the luminal surface as well as side branches that may induce a curve in the distal wire. Clinical significance: The preliminary experience obtained in this feasibility trial confirmed that IVUS and the Flowire may be combined to assess both candidate lesions as well as postprocedural patency in patients undergoing percutaneous revascularization. The combination of physiologic and anatomic data available from IVUS and the Flowire provides a far more sensitive and possibly more accurate analysis of the adequacy of revascularization than has been possible by angiography alone. The extent to which such detailed investigation is required to optimize interventional therapy on a routine basis is subject to subsequent studies.

F Honye .I, Mahon DJ, Jain A, White CJ, Ramee SR, Wallis JB, AI-Zarka A, Tobis JM. Morphological effects of coronary balloon aneioolr&v in viva assesscd by intravascular ultrasound imaging. Circulation 1992,85:1012-1025. 2. Isner JM, Rosenfield K, Kelly K, Losordo DW, DeJesus ST, Palefsky P, Lang&n RI?, Razvi S, Pastore JO, Kowwsky BD. Percutaneous intravascular ultrasound examination as an adjunct to catheter-based intewentions: preliminary experience in patients with peripheral vascular disease. RaLiiorogv 1990;175: 61-70. 3.Isner JM, Rosenfield K, Losordo DW, Rose L, Langevin RE, Razvi S, Kosowsky BD. Combination balloon-ultrasound imaging catheter for percutaneous transluminal angioplasty. Cixxlatin 1991;84:73%754. 4. Losordo DW, Rosenfield K, Pieczek A, Baker K, Harding M, Isner JM. How does angioplasty work? Serial analysis of human iliac arteries using intravascular ultrasound. C&&ion 1992;86:184.%1858. 5. Mecley M, Rosenfield K, Kaufman J, Langevin RE, Razvi S, Isner JM. Atherosclerotic plaque hemorrhage and rupture associated with crescendo claudication. Ann Intern Med 1992;117:663&%. 6. Yock PG, Fitzgerald PJ, Liier DT, Angelsen BA. Intravascular ultrasound guidance for catheter-based coronary interventions. JAm Coil Cm&l 19M,17: 39545B. 7. Potkin BN, Keren G, Mintz GS, Douek PC, Pichard AD, Satler LF, Kent KM, Leon MB. Arterial responses to balloon coronary angioplasty: an intravascular ultrasound study. JAm Co11 Cardid 1992;20942-951. 8. The SHK, Gussenhoven EJ, Zhong Y, Li W, van Egmond FC, Pietetman H, van Urk H, Gerritsen GP, Borst C, Wilson RA, Born N. Effect of balloon angioplasty on femoral artery evaluated with intravascular ultrasound imaging. Circulation 1992,86:483-493. 9. Rosenfield K, Losordo DW, Ramaswamy K, Pastore JO, Langevin RE, Rti S, Kosowsky BD, Isner JM. Three-dimensional reconstruction of human

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coronary and peripheral arteries from images recorded during two-dimensional intravascular ultrasound examination. C&x&u?o~ 1991;84:19361956. l0. Tenaglia AN, Buller CE, Kisslo KB, Stack RS, Davidson CJ. Mechanisms of balloon angioplasty and directional coronary atherectomy as assessed by intracoronary ultrasound. Am J Car&[ 1992;20:685~91. Li. Rosenfield K, Voelker W, Losordo DW, Ramaswamy K, Kosowsky BD, Pastore JO, Isner JM. Assessment of coronary arterial stenoses postintervention by quantitative angiography versus intracoronary ultrasound in 13 patients undergoing balloon and/or laser coronary angioplasty (Ahstr.) J Am Co11 Cardiol 1991; 17:46A. 12. Isner JM, Rosenfield K. Enough with the fantastic voyage: will IVUS pay in Peoria? Cathet Cardiovasc Diagn 1992;26:192-199. 13. Gurley JC, Nissen SE, Grines CL, Booth DC, Fischer D, DeMaria AN. Comparison of intravascular ultrasound and angiography following percutaneous transluminal coronary angioplasty. (Ahstr.) Circulation 1990,82:III-72. 14. Segal J, Kern MJ, Scott NA, King SB III, Doucette JW, Heuser RR, Ofili E, Siegel R. Alterations of phasic coronary artery flow velocity in humans during percutaneous coronary angioplasty. JAm Co// Cardiol1992;20:27&286. 15. Segal J, Lundergan CF. Determination of the hemodynamic significance of coronary artery stenoses of intermediate severity. Am Hemt J 1992;124:10731077. 18. Kaufman J, Pieczek A, GraJl E, Rosenfield K. Direct intravascular measurement of flow velocity using an ,018” Doppler guidewire provides a potential physiologic endpoint during percutaneous revascularization of peripheral arteries. (Abstr.) Circu/&wz 1992;86:1-245. 17. Doucette JW, CorI D, Payne HM, Flynn AE, Goto M, Nassi M, Segal J. Validation of a Doppler guidewire for intravascular measurement of coronary artery flow velocity. Circulation 1992;85:1899-1911. 18. Ofili E, Kern MJ, Tatineni S, Deligonul U, Aguirre F, Serota H. Labwitz AJ. Detection of coronary collateral Row by a Doppler-tipped guidewire during coronary angioplasty. Am HeatfJ 1991;122:221-22.5. 19. Donahue TJ, Kern MJ, Aguirre N, Bell C, Penick D, Segal J, Otili E, Heuser R. Determination of the hemodynamic significance of angiographically

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intermediate coronary stenoses by intracoronary Doppler flow velocity. (Ahstr.) JAm CON Caniiol1992;19:242A. 20. Ofili EO, Karim AM, Kern JJ, Deligonul U, Aguirre F, Serota H, Tatineni S. Simultaneous comparison of intracoronary spectral and zero-cross flow velocity measurements by Doppler angioplasty guidewire and catheter techniques. (Ahstr.) JAm CON Cardiol 1991;17A:124A. 21. Arnett EN, Isner JM, Redwood CR, Kent KM, Baker W, Ackarstein H, Roberts WC. Coronary artery narrowing in coronary heart disease: comparison of cineangiographic and necropsy findings, Am Inion Med 1979;91:35@356. 22. Isner JM, Kishel J, Kent KM, Ronan JA, Jr., Ross AM, Roberts WC. Accuracy of angiographic determination of left main coronary arterial narrowing: angiographic-histologic correlative analysis in 28 patients. Circularion 1981; 63:105&1064. 23. Isner JM, Donaldson RF. Coronary angiographic and morphologic correlation. Cardio[ Clin 1984;2:571-592. 24. Dietz WA, Tohis JM, Isner JM. Failure of angiography to accurately depict the extent of coronary artery narrowing in three fatal cases of percutaneous transluminal coronary angioplasty. J Am Coil Cardiol 1992;19:1261-1270. 25. Nissen SE, Gurley JC, Grines CL, Booth DC, McClure R, Berk M, Fischer C, DeMaria AN. Intravascular ultrasound assessment of lumen size and wall morphology in normal subjects and patients with coronary artery disease. Circularion 1991;84zlO87-1099. 26. Kleiman NS, Raizner AE, Roberts R. Percutaneous transluminal coronary angioplasty: is what we see what we get? J Am CM Cardial 1990,16:576-577. 27. Isner JM, Rosenfield K, Losordo DW, Pieczek A. Intravascular ultrasound: potential for optimizing mechanical solutions to restenosis. In: Serruys PW, Strauss BH, King SB III, eds. Restenosis after intervention with new mechanical devices. Dordrecht: Kluwer Academic Publishers, 199211 l-148. 28. Gal D, Kaufman J, Pieczek G Rosenfield K, Isner JM. New means to monitor reperfusion on-line: experimental studies in rabbit model and initial human application during pharmacologic thrombolysis of occluded bypass grafts. (Abstr.) Circulation 1992;86:1-650.

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