(Stroke. 1997;28:574-579.)
© 1997 American Heart Association, Inc.
Articles |
From the Division of Clinical Neuroscience, St George's Hospital Medical School (F.C., M.M.B.); Department of Neuroradiology, Atkinson Morley's Hospital (A.C.); and Department of Neurology, King's College School of Medicine and Dentistry (H.M.), London, UK.
Correspondence to Dr Martin M. Brown, Division of Clinical Neuroscience, St George's Hospital Medical School, Cranmer Terrace, London, SW17 ORE, UK. E-mail mbrown{at}sghms.ac.uk.
| Abstract |
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Methods Twelve patients with symptomatic carotid stenosis were treated by PTA, and the anatomic result was studied by digital subtraction angiography at 1 year, supplemented by duplex ultrasound examinations at 1 month and 6 months.
Results The mean severity of stenosis treated, measured by
the common carotid method, was 82% (range, 69% to 98%). The
immediate result of PTA was a reduction in the severity of stenosis in
all patients to a mean of 51% (P<.005). Six of the 12
patients showed a further improvement in lumen diameter of
14% at
1-year angiographic follow-up from a mean stenosis of 47% (range, 24%
to 76%) immediately after PTA to 28% (range, 0% to 52%) at 1 year.
This indicates an active process of remodeling in response to carotid
PTA. PTA initially reduced the stenosis by
20% in 9 of the 12
arteries, and 8 of these remodeled or remained largely unchanged
compared with only 1 of the 3 with a suboptimal initial dilation. In 3
patients the lumen diameter improved by <5%. Three other patients
restenosed with an increase in stenosis after PTA of 9%, 16%, and
66% at 1 year, but all were asymptomatic. The duplex findings showed
that remodeling occurred at variable times between PTA and 1 year.
Conclusions Remodeling of the carotid artery after PTA has not been described before. Our results confirm that carotid angioplasty has an acceptable patency rate at 1 year. It has been suggested that endovascular treatment of carotid stenosis should include placement of a stent. Our results indicate that this may not be necessary unless the initial PTA result is a reduction in stenosis of <20%.
Key Words: angioplasty carotid stenosis stents
| Introduction |
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A number of centers are starting to treat carotid stenosis by PTA, and randomized, controlled trials are in progress.3 Retrospective studies suggest that the immediate risks of carotid PTA are similar to those of surgery,4 but the long-term efficacy of the procedure in dilating the carotid artery has not been established. Our initial experience suggested that PTA of the carotid by balloon dilation in patients with severe carotid stenosis did not always result in full dilation of the artery. If dilation reduced a stenosis of 90% to 50%, we were uncertain whether this initial incomplete dilation would restenose, remodel, or remain unchanged. Furthermore, restenosis after PTA is a problem at other sites5 6 and results in both expense of retreatment and inconvenience to the patient.
Stents have been used in the coronary circulation for 10 years.7 Randomized controlled trials of coronary stenting versus angioplasty have shown that stenting reduces the 6-month restenosis rate by 40%,8 9 but only one trial has shown sustained clinical benefit with stenting.10 It has been suggested that stenting should be the interventional treatment of choice for carotid stenosis because the initial results are superior.11 12 13
We noted the improvement in diameter of the carotid artery that occurred in some patients with an initially incomplete dilation after simple balloon PTA, indicating a remodeling process in the carotid artery, which had not been described previously. This suggested that an initially suboptimal result after PTA might not necessarily indicate a need for stenting. To obtain an accurate measure of the anatomic outcome of carotid PTA, we performed follow-up DSA 1 year after carotid PTA in a series of 12 patients with carotid stenosis. DSA was supplemented by duplex ultrasound at intervening intervals to assess the time course of the anatomic changes. We therefore report the results in our first 12 patients and discuss the mechanisms.
| Subjects and Methods |
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The study was approved by the district ethics committee, and informed consent was obtained from all patients. All patients were pretreated with aspirin (300 mg/d) before angioplasty.
A 6F sheath was inserted into the right femoral artery, then a 5F guiding catheter was inserted into the appropriate CCA. After systemic heparinization (heparin 5000 IU IV), the stenosis was crossed with either a standard or hydrophilic wire. The guide catheter was passed across the stenosis. After we ascertained that the guide catheter was intraluminal, an exchange wire was placed through the guide catheter distal to the stenosis and an angioplasty catheter exchanged across the stenosis. A 100-cm-long Optiplast Vascath (5F shaft, with balloon 2 cm long and 5, 6, or 7 mm in diameter, depending on the diameter of the normal ICA) was used to dilate the stenosis. Hand inflation was performed up to three times for a duration of up to 30 seconds depending on the visual results seen on fluoroscopy. The balloon catheter was then removed, and a check angiogram was performed. Anticoagulation (heparin 20 000 U/24 h) was continued for 48 hours after PTA. During the procedure a simple neurological examination was performed, and electrocardiogram and blood pressure were monitored.
All patients were discharged on aspirin, with the exception of the 1 patient in atrial fibrillation who was taking warfarin. All the procedures, including follow-up DSA, were performed by an experienced consultant interventional neuroradiologist. Follow-up DSA was limited to two views of the treated site, chosen to reproduce the projections used to demonstrate the original stenosis at the first procedure.
The severity of stenosis was analyzed on two separate occasions with the use of the NASCET, ECST, and CCA methods14 by one observer with extensive experience in using all three methods of measuring carotid stenosis. The angiographic projection showing the most severe degree of stenosis on the initial angiogram and views as close as possible in projection angle to this initial view were selected for measurement by one of the authors. The remaining views and printed text were then masked so that the observer making the measurements was blind to the name of the patient and to whether the angiogram was before, immediately after, or 1 year after PTA. The angiograms of the 1 patient with distal ICA stenosis did not include views of the carotid bifurcation or CCA, and the diameter of the largest visible normal portion of the ICA was used as the denominator.
Eleven patients had duplex ultrasound studies of the CCA and ICA before
PTA and at 1 month, 6 months, and 1 year after PTA. Seven also had
duplex studies 2 days after PTA. It was not possible to insonate the
site of stenosis in the 1 patient (patient 5) with a distal ICA
stenosis. We used Doppler ultrasound to measure the ICA peak systolic
velocity at the site of maximum stenosis and the CCA end-diastolic
velocity. An ICA peak systolic velocity of
1.2 m/s indicated a
stenosis of <50%, and CCA end-diastolic velocity was not recorded in
these examinations. Stenoses of
50% were determined in increments of
10% by the ratio of the ICA peak systolic velocity to the CCA
end-diastolic velocity.15 This ratio shows a nonlinear
relationship with ICA percent diameter reduction on angiography. In
cases of critical stenosis, the peak systolic velocity may be reduced
to "normal" since little blood can get through such a tight
lesion. All duplex ultrasound examinations were taped and subsequently
were analyzed by a single observer blind to the date of the
recording.
Statistical Analysis
Paired t tests were performed to compare the
intraobserver variability in measuring the stenoses and the change in
percent stenosis after PTA. Significance was declared at the
P<.05 level.
| Results |
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The immediate result of PTA was an improvement in angiographic patency
in all vessels from a mean stenosis of 82% before PTA to 51%
immediately afterward (P<.005) (Table 1
).
Six of the 12 patients showed a further improvement in lumen diameter
of
14% at 1-year angiographic follow-up from a mean stenosis of 47%
(range, 24% to 76%) immediately after PTA to 28% (range, 0% to
52%) at 1 year (P=.007). The Figure
shows
this process of remodeling in patient 3. In 3 patients (patients 6, 9,
and 11), the stenosis remained largely unchanged. The other 3 patients
(patients 4, 7, and 12) showed restenosis between the PTA procedure and
1-year follow-up.
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Two of the 3 patients who restenosed had a poor initial angiographic
result, with only a 19% and 15% improvement in the initial stenosis
immediately after PTA. The degree of restenosis was relatively minor
with an increase in residual stenosis of only 9% and 16%, but because
of the poor initial result this resulted in the stenoses just reaching
a severe degree of 70% and 75%. The only other patient in whom PTA
reduced the stenosis immediately by <20% (patient 6) showed only a
2% improvement in stenosis over the course of the next year. The 9
remaining patients had an initial improvement in stenosis immediately
after PTA of >20% (Table 1
). Eight of these subsequently remodeled,
and only 1 restenosed.
The ultrasound findings before PTA agreed substantially with the
results of the initial DSA except in patient 2, in whom the ultrasound
suggested that the stenosis was only 50% to 59% rather than 71%, as
shown with DSA. Peak systolic velocity was appropriately high in all of
the stenoses shown by DSA to be >90% (patients 3, 5, and 9).
Ultrasound does not reliably distinguish between grades of stenosis
<50%. In the 3 patients with 50% to 59% stenosis on DSA at 1-year
follow-up and the 6 with <50% stenosis, ultrasound estimated the
stenosis to be <50%. In the 3 patients with >60% stenosis at 1 year
on DSA, the ultrasound measurements agreed within 20%. Table 2
shows the change in stenosis as measured with Doppler
over time. Both remodeling and restenosis appeared to occur at various
times after PTA.
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No patient suffered a stroke or transient ischemic attack during the procedure or during follow-up.
| Discussion |
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This is the first time that remodeling of carotid arteries has been described. Our results confirm that carotid angioplasty has an acceptable patency rate at 1 year and should encourage further studies of the procedure. It has been suggested that an incomplete dilation of the carotid artery after attempts at balloon dilation is an indication for insertion of a stent. Our results suggest that this is not necessary in the majority of patients unless PTA has resulted in a <20% reduction in stenosis when we now consider inserting a stent or another attempt at dilation. We would also consider stenting when the lesion is heavily calcified or there is spasm immediately after PTA. Studies comparing both the clinical and anatomic outcomes of stents and simple balloon dilation are required.
DSA was chosen as the gold standard to measure the outcome of the
procedure because it was believed to be essential at this early stage
of the development of carotid PTA to establish that the procedure
resulted in a satisfactory anatomic result and obtain an accurate
measure of the anatomic outcome despite the risks of angiography. In
this study the risks were minimized as far as possible by limiting the
follow-up angiography to two views, and all angiograms were performed
by an experienced consultant neuroradiologist. We do not advocate
routine follow-up invasive arteriography after carotid angioplasty, but
we believed it was in the best interests of our first patients to know
whether they had benefited from the procedure. When we started the
study there was considerable doubt about the accuracy of duplex
examination,16 and it was uncertain whether it would
adequately detect fibrotic restenosis because we suspected this might
be echolucent. This small series shows that in our experience duplex
was reliable both before and after PTA at detecting stenosis of
60%
and misclassified only 1 of 14 stenoses, consistent with the results of
more recent series. Until recently there was considerable doubt as to
whether stenoses of between 30% and 70% would warrant treatment, but
the results of the ECST suggest that patients with <70% stenosis
(measured by the ECST or CCA method) do not require
intervention.17 In the future we will rely on a
combination of ultrasound and MR angiography to assess outcome after
PTA.
We did not perform statistical analyses at 1 year because we had an a priori hypothesis that there would be two subgroups of arteries: those that remodeled and those that restenosed. Statistical analysis of all 12 patients together at this time interval would therefore have been inappropriate, but to analyze the reduction in stenosis in those who had remodeled and the increase in stenosis in those who had restenosed would almost certainly be significant and therefore meaningless.
The CCA method that we used to measure stenosis severity has previously been shown to be the most reproducible of the three methods.14 A study of diseased carotid arteries has shown that the ECST denominator and CCA lumen are on average exactly equivalent (ratio, 1.00; 95% confidence interval, 0.71 to 1.41),18 confirming that results of measuring stenosis by the CCA method can be considered to produce values equivalent to those obtained by the ECST method.
Much work has been done on the identification and mechanisms of remodeling and restenosis at other sites since this is important in terms of both patient morbidity and economics. The process of atherosclerosis involves plaque formation in the intima which, because of the elastic nature of the outer layers of wall, bulges into the vessel lumen. Angioplasty subjects vessel walls to barotrauma. The result of this has been studied both in animals and in human cadavers, including rabbit aortas and iliac arteries and dog19 and human20 coronary vessels. The effects of PTA vary between species and sites, but in human coronary and rabbit iliac arteries the atherosclerotic plaque is cracked and split, the overlying endothelium is denuded, and the intima and plaque are dehisced from the underlying media. The media and adventitia are stretched or torn. The force of the angioplasty balloon can overcome the now nonelastic wall, and therefore the vessel dilates aneurysmally. The result is that the lumen is enlarged.21 Some degree of dissection probably occurs and may be essential to achieve dilation.22
Remodeling and restenosis of arteries can be considered to be part of the same process.23 PTA has been described as controlled injury24 ; the resultant damaged artery responds to this trauma. If this physiological response is too great, it results in pathological vessel lumen renarrowing. If the response is less prolific, the lumen may be enlarged compared with the diameter immediately after PTA. Forrestor et al25 have proposed a mechanism of remodeling and restenosis based on the wound healing process. They suggest that inflammation occurs from the time of PTA for approximately 10 days, granulation from days 2 to 20, and matrix remodeling from day 10 onward. This is supported by Nobuyoshi et al,26 who studied coronary artery histology at postmortem examinations of 20 patients dying several hours to 4 years after percutaneous transluminal coronary angioplasty. They found thrombus in lesions up to 1 month after the procedure but very little thereafter. Intimal proliferation of smooth muscle cells was seen between 11 days and 2 years; the extent was higher in lesions with a medial or adventitial tear. This would suggest that restenosis is related to the amount of tear produced. They also noted that smooth muscle cells changed from the synthetic to the contractile type after 6 months and that after 2 years the intimal proliferation was replaced by fibrotic tissue. This may be the mechanism by which our series of carotid arteries have enlarged after PTA. Duplex ultrasound showed remodeling at various times after PTA, but the follow-up was not long enough to indicate when this process ceases and whether restenosis may occur after 1 year.
Kuntz et al27 concluded that a better immediate coronary PTA result is indicative of a more patent lumen at follow-up. Beatt et al28 add support to their findings, as do two randomized, controlled trials comparing coronary stents with balloon angioplasty. The stented group showed a better initial result and a larger lumen at 6-month angiographic follow-up, but in this group there was also more intimal hyperplasia and lumen loss from the post-PTA state than in the angioplasty group.8 9 Our results suggest that carotid arteries behave differently from coronary arteries since 9 of the 12 patients showed a further improvement in lumen diameter at 1 year from that achieved with the initial dilation. This suggests that stenting carotid arteries to improve an initial incomplete dilation is not necessary to produce a satisfactory increase in lumen diameter unless the stenosis has been reduced by <20%. The proposal that carotid artery stenosis should always be treated by stenting rather than balloon angioplasty11 12 13 is not supported by our results, although our follow-up in this study is limited to 1 year. It is feasible that stenting will have other advantages, such as a lower complication rate, which can only be determined by clinical trials.
In conclusion, our results provide the first angiographically confirmed data that remodeling occurs after carotid PTA and that this results in a satisfactory lumen in the majority of patients. In our series of 12 patients 3 restenosed, but they were asymptomatic. The results confirm that PTA provides a feasible alternative to carotid endarterectomy and that carotid stenting may be unnecessary in the majority of cases. Longer follow-up and the results of large multicenter, randomized trials, such as CAVATAS (Carotid and Vertebral Artery Transluminal Angioplasty Study), are needed to establish the risks and benefits of PTA compared with conventional surgery or medical care.
| Selected Abbreviations and Acronyms |
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| Acknowledgments |
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Received October 4, 1996; revision received November 21, 1996; accepted December 13, 1996.
| References |
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2. European Carotid Surgery Trialists' Collaborative Group. MRC European Carotid Surgery Trial: interim results for symptomatic patients with severe (70-99%) or with mild (0-29%) carotid stenosis. Lancet. 1991;337:1235-1243. [Medline] [Order article via Infotrieve]
3. Brown MM, Clifton A, Buckenham T, Taylor RS. Carotid and vertebral artery transluminal angioplasty study: pilot study. Cerebrovasc Dis.. 1995;5:268. Abstract.
4. Brown MM. Balloon angioplasty for cerebrovascular disease. Neurol Res. 1992;4(suppl):159-173.
5.
Landau C, Lange RA, Hillis LD. Percutaneous
transluminal coronary angioplasty. N Engl J
Med.. 1994;330:981-993.
6.
Johnston KW. Femoral and popliteal arteries:
reanalysis of results of balloon angioplasty.
Radiology. 1992;183:767-771.
7. Eeckhout E, Kappenberger L, Goy JL. Stents for intracoronary placement: current status and future directions. J Am Coll Cardiol.. 1996;27:757-765. [Abstract]
8.
Serruys PW, DeJaegere P, Kiemeneij F, Macaya C, Rutsch
W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P, Belardi
J, Sigwart U. A comparison of balloon-expandable-stent
implantation with balloon angioplasty in patients with coronary artery
disease. N Engl J Med.. 1994;331:489-495.
9.
Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP,
Penn I, Detre K, Veltri PHL, Ricci D, Nobuyoshi M, Cleman M, Heuser R,
Almond D, Teirstein PS, Fish D, Colombo A, Brinker J, Moses J,
Shaknovich A, Hirshfield J, Bailey S, Ellis S, Rake R Goldberg
S. A randomised comparison of coronary-stent placement and
balloon angioplasty in the treatment of coronary artery
disease. N Engl J Med.. 1994;331:496-501.
10. Macaya C, Serruys PW, Suryapranta H. One year clinical follow up of the Benestent Trial. J Am Coll Cardiol.. 1995;25:374A. Abstract.
11. Roubin GS, Yadav S, Iyer SS, Vitek J. Carotid stent-supported angioplasty: a neurovascular intervention to prevent stroke. Am J Cardiol.. 1996;78:8-12.
12. Theron J. Protected carotid angioplasty and carotid stents [in French]. J Mal Vasc. 1996;21(suppl A):113-122.
13. Bergeron P, Chambran P, Hartung O, Bianca S. Cervical carotid artery stenosis: which technique, balloon angioplasty or surgery? J Cardiovasc Surg. 1996;37(suppl 1):73-75.
14. Rothwell PM, Gibson RJ, Slattery J, Warlow CP. Prognostic value and reproducibility of measurements of carotid stenosis. Stroke. 1994;25:2440-2444. [Abstract]
15. Williams MA, Deacon DFS, Szendro G, Belcaro G, Nicolaides AN, Salmasi AM, Nicolaides AN, eds. Cardiovascular Applications of Doppler Ultrasound. New York, NY: Churchill Livingstone, Inc; 1988:247-260.
16.
Eliasziw M, Rankin RN, Fox AJ, Haynes RB, Barnett
HJM. Accuracy and prognostic consequences of ultrasonography in
identifying severe carotid stenosis. Stroke. 1995;26:1747-1753.
17. European Carotid Surgery Trialists' Collaborative Group. Endarterectomy for moderate symptomatic carotid stenosis: interim results from the MRC European Carotid Surgery Trial. Lancet. 1996;347:1591-1593. [Medline] [Order article via Infotrieve]
18. Rothwell PM, Gibson RJ, Slattery J, Sellar RJ, Warlow CP. Equivalence of measurements of carotid stenosis: a comparison of three methods on 1001 angiograms: European Carotid Surgery Trialists' Collaborative Group. Stroke. 1994;25:2435-2439. [Abstract]
19. Block PC, Fallon JT, Elmer D. Experimental angioplasty: lessons from the laboratory. AJR Am J Roentgenol. 1980;135:907-912. [Abstract]
20. Karas SP, Santoian EC, Gravanis MB. Restenosis following coronary angioplasty. Clin Cardiol.. 1991;14:791-801. [Medline] [Order article via Infotrieve]
21. McBride W, Lange RA, Hillis LD. Restenosis after successful coronary angioplasty, pathophysiology and prevention. N Engl J Med.. 1988;318:1734-1737. [Medline] [Order article via Infotrieve]
22. Waller BF, Orr CM, Pinkerton CA, VanTassel JW. Morphological observations late after balloon angioplasty: mechanisms of acute injury and relationship to restenosis. Radiology. 1990;174:961-967. [Abstract]
23. Haudenschild CC. Pathobiology of restenosis after angioplasty. Am J Med. 1993;94(suppl 4A):40-44.
24.
Serruys PW, Luijten HE, Beatt KJ, Geuskens R, DeFeyter
PJ, van den Brand M, Reiber JHC, ten Katen HJ, Hugenholtz PG.
Incidence of restenosis after successful coronary angioplasty: a time
related phenomenon. Circulation. 1988;77:361-371.
25. Forrester JS, Fishbein M, Helfant R, Fagin J. A paradigm for restenosis based on cell biology: clues for the development of new preventive therapies. J Am Coll Cardiol.. 1991;17:758-769. [Abstract]
26. Nobuyoshi M, Kimura T, Ohishi H, Horiuchi H, Nosaka H, Hamasaki N, Yokoi H, Kim K. Restenosis after percutaneous coronary angioplasty: pathological observations in 20 patients. J Am Coll Cardiol.. 1991;17:433-439. [Abstract]
27. Kuntz RE, Gibson CM, Nobuyoshi M, Baim DS. Generalised model of restenosis after conventional balloon angioplasty, stenting and directional atherectomy. J Am Coll Cardiol.. 1993;21:15-25. [Abstract]
28. Beatt KJ, Serruys PW, Luijten HE, Rensing BJ, Suryapranta H, de Feyter P, van den Brand M, Laarman GJ, Roelandt J. Restenosis after coronary angioplasty: the paradox of increased lumen diameter and restenosis. J Am Coll Cardiol.. 1992;19:258-266.[Abstract]
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