2
Editorial Comment Too Much May Be Too Much Raoul Bonan, MD Montreal Heart Institute, Montreal, Quebec, Canada The new disease of the last decade, in-stent restenosis, is a significant clinical problem despite the dramatic decrease in the need for repeat intervention following stenting as compared to conventional angioplasty. In- stent restenosis results from neointima proliferation, which protrudes through stent strut and will create sig- nificant lumen narrowing. It has been found that this proliferation contains few cells and is predominantly matrix. Elastic compression and its correlate, instant re- stenosis, have been described by Waksman. Having solved the problem of stent thrombosis with antiplatelet therapy regimens, a stent still needs to be fully deployed to improve the mid-and long-term angio- graphic and clinical outcome. Angiography is only an evaluation of a shadow; study of intravascular ultrasound has demonstrated that despite optimal angiographic “shadow” results, a significant number of stents are not perfectly deployed [1]. Several IVUS criteria have eval- uated stent expansion [2]. More needs to be done to understand the role of stent underdeployment and, spe- cifically, its association with in-stent restenosis [3]. Stan- dard IVUS criteria have permitted recognition of only 20 – 40% of underdeployed stents among patients with clinical in-stent restenosis referred to brachytherapy. IVUS-guided repeat PTCA may improve further deploy- ment irrespective of any stent underdeployment criteria [4]. The article by Wu et al. [5] provides specific insights into in-stent restenosis pathology and treatment. The first lesson will be the confirmation of the notion of late loss index in the in-stent restenosis treatment. The authors’ correlation between the postintervention minimum lu- men area and the follow-up minimum lumen area, estab- lish a relationship between the injury, the postinterven- tion lumen minimum area (MLA) and the response, the follow-up MLA. It is interesting that it can be reproduced with an in-stent restenosis model not only in animal but also in human. The second lesson, using a new IVUS late loss index, confirms again the impact of radiation on the mid-term outcome of an in-stent restenosis treatment. Prior to this study, five randomized placebo-controlled trials have established that beta-and gamma-radiation reduced the incidence of restenosis in clinical events following the treatment of in-stent restenosis. Treatment effect of any kind of radiation was over 30% for any analyzed parameter with similar benefits for beta-emitter (Sr 90 and P 32 ) and gamma-emitter [6 –12]. Unfortunately, in this study, an interesting IVUS-re- lated contribution to the pathology and treatment of in- stent restenosis was missing. Since it was a retrospective study, an expansion of the stent was not carried out and therefore its impact on the follow-up was not possible. Without the minimum stent area at follow-up, a variation of the potential negative remodeling on the stent at fol- low-up and its difference between the placebo group and the radiation group cannot be evaluated. With radiation treatment of restenosis, we have learned to look wide and not only evaluate the lesion site to understand the relation between the injury and the dose, but more importantly to evaluate the fall-off dose length. IVUS edge studies still need to be done. Figure 2 of this study reveals an interesting correlation between the mean follow-up percentage of intimal hy- perplasia and the cross-sectional area, and the mean increase in intimal hyperplasia and the cross-sectional area, with the postintervention percentage of intimal hy- perplasia and cross-sectional area for both placebo and irradiated patients. This relationships revives the notion that too much may be too much and we need to evaluate where stent expansion reaches a balance between too much injury and enough lumen-opening treatment. The ratio and relationship between baseline intimal hyperpla- sia postintervention versus baseline intimal hyperplasia preintervention probably should be indexed to the refer- ence vessel diameter or the mean stent area; this may guide the treatment of in-stent restenosis. Finally, IVUS is surely underutilized and all the studies have shown its benefits at the time of the stent implantation and its capability to bring the restenosis rate into single digits [2]. In the treatment of in-stent restenosis, we must recognize the pitfall of underdeployment and need to In accordance with the policy of the Journal, the designated author discloses a financial or other interest in the subject discussed in this article. DOI 10.1002/ccd.10676 Published online in Wiley InterScience (www.interscience.wiley.com). Catheterization and Cardiovascular Interventions 60:489 – 490 (2003) © 2003 Wiley-Liss, Inc.

Too much may be too much

Embed Size (px)

Citation preview

Page 1: Too much may be too much

Editorial Comment

Too Much May Be Too Much

Raoul Bonan,† MD

Montreal Heart Institute,Montreal, Quebec, Canada

The new disease of the last decade, in-stent restenosis,is a significant clinical problem despite the dramaticdecrease in the need for repeat intervention followingstenting as compared to conventional angioplasty. In-stent restenosis results from neointima proliferation,which protrudes through stent strut and will create sig-nificant lumen narrowing. It has been found that thisproliferation contains few cells and is predominantlymatrix. Elastic compression and its correlate, instant re-stenosis, have been described by Waksman.

Having solved the problem of stent thrombosis withantiplatelet therapy regimens, a stent still needs to befully deployed to improve the mid-and long-term angio-graphic and clinical outcome. Angiography is only anevaluation of a shadow; study of intravascular ultrasoundhas demonstrated that despite optimal angiographic“shadow” results, a significant number of stents are notperfectly deployed [1]. Several IVUS criteria have eval-uated stent expansion [2]. More needs to be done tounderstand the role of stent underdeployment and, spe-cifically, its association with in-stent restenosis [3]. Stan-dard IVUS criteria have permitted recognition of only20–40% of underdeployed stents among patients withclinical in-stent restenosis referred to brachytherapy.IVUS-guided repeat PTCA may improve further deploy-ment irrespective of any stent underdeployment criteria[4].

The article by Wu et al. [5] provides specific insightsinto in-stent restenosis pathology and treatment. The firstlesson will be the confirmation of the notion of late lossindex in the in-stent restenosis treatment. The authors’correlation between the postintervention minimum lu-men area and the follow-up minimum lumen area, estab-lish a relationship between the injury, the postinterven-tion lumen minimum area (MLA) and the response, thefollow-up MLA. It is interesting that it can be reproducedwith an in-stent restenosis model not only in animal butalso in human. The second lesson, using a new IVUS lateloss index, confirms again the impact of radiation on themid-term outcome of an in-stent restenosis treatment.

Prior to this study, five randomized placebo-controlledtrials have established that beta-and gamma-radiationreduced the incidence of restenosis in clinical eventsfollowing the treatment of in-stent restenosis. Treatmenteffect of any kind of radiation was over 30% for anyanalyzed parameter with similar benefits for beta-emitter(Sr90 and P32) and gamma-emitter [6–12].

Unfortunately, in this study, an interesting IVUS-re-lated contribution to the pathology and treatment of in-stent restenosis was missing. Since it was a retrospectivestudy, an expansion of the stent was not carried out andtherefore its impact on the follow-up was not possible.Without the minimum stent area at follow-up, a variationof the potential negative remodeling on the stent at fol-low-up and its difference between the placebo group andthe radiation group cannot be evaluated. With radiationtreatment of restenosis, we have learned to look wide andnot only evaluate the lesion site to understand the relationbetween the injury and the dose, but more importantly toevaluate the fall-off dose length. IVUS edge studies stillneed to be done.

Figure 2 of this study reveals an interesting correlationbetween the mean follow-up percentage of intimal hy-perplasia and the cross-sectional area, and the meanincrease in intimal hyperplasia and the cross-sectionalarea, with the postintervention percentage of intimal hy-perplasia and cross-sectional area for both placebo andirradiated patients. This relationships revives the notionthat too much may be too much and we need to evaluatewhere stent expansion reaches a balance between toomuch injury and enough lumen-opening treatment. Theratio and relationship between baseline intimal hyperpla-sia postintervention versus baseline intimal hyperplasiapreintervention probably should be indexed to the refer-ence vessel diameter or the mean stent area; this mayguide the treatment of in-stent restenosis. Finally, IVUSis surely underutilized and all the studies have shown itsbenefits at the time of the stent implantation and itscapability to bring the restenosis rate into single digits[2]. In the treatment of in-stent restenosis, we mustrecognize the pitfall of underdeployment and need to

†In accordance with the policy of the Journal, the designated authordiscloses a financial or other interest in the subject discussed in thisarticle.

DOI 10.1002/ccd.10676Published online in Wiley InterScience (www.interscience.wiley.com).

Catheterization and Cardiovascular Interventions 60:489–490 (2003)

© 2003 Wiley-Liss, Inc.

Page 2: Too much may be too much

monitor the injury effect of overdeployment of the treat-ment. IVUS may yet serve to improve on the treatment,even with the use of radiation therapy, of this newdisease.

REFERENCES

1. Albiero R, Rau T, Schluter M, et al. Comparison of immediate andintermediate-term results of intravascular ultrasound versus an-giography-guided Palmaz-Schatz stent implantation in matchedlesions. Circulation 1997;96:2997–3005.

2. de Jaegere P, Mudra H, Figulla H, et al. Intravascular ultrasound-guided optimized stent deployment: immediate and 6 monthsclinical and angiographic results from the Multicenter UltrasoundStenting in Coronaries Study (MUSIC study). Eur Heart J 1998;19:1214–1223.

3. Castagna MT, Mintz GS, Leiboff BO, et al. The contribution of“mechanical” problems to in-stent restenosis: an intravascularultrasonographic analysis of 1090 consecutive in-stent restenosislesions. Am Heart J 2001;142:970–974.

4. De Larochelliere R, Bertrand OF, Joyal M, et al. Incidence of stentunder-deployment as a cause of in-stent restenosis. J Am CollCardiol 2002;39(Suppl A):34A.

5. Wu Z, McMillan TL, Mintz GS Maehara A, Canos D, Bui AB,Waksman R, Weissman NJ. The impact of the acute results on thelong-term outcome after the treatment of in-stent restenosis: a

serial intravascular ultrasound study. Cathet Cardiovasc Intervent2003;60:483–488.

6. Teirstein PS, Massullo V, Jani S, et al. Catheter-based radiother-apy to inhibit restenosis after coronary stenting. N Engl J Med1997;336:1697–1703.

7. Waksman R, White RL, Chan RC, et al. Intracoronary radiationtherapy after angioplasty inhibits recurrence in patients with in-stent restenosis. Circulation 2000;101:2165–2171.

8. Leon MB, Teirstein PS, Moses JW, et al. Localized intracoronarygamma-radiation therapy to inhibit the recurrence of restenosisafter stenting. N Engl J Med 2001;344:250–256.

9. Popma J, Suntharalingam M, Lansky A, et al., for the STARTinvestigators. A randomized trial of 90strontium/9oyttrium betaradiation versus placebo control for the treatment of in-stentrestenosis. Circulation 2002;106:1090–1096.

10. Waksman R, Raizner A, Yeung A, et al. Use of localized intra-coronary beta radiation in treatment of in-stent restenosis: theINHIBIT randomized control trial. Lancet 2002;359:551–557.

11. Waksman R, Chenau E, Ajani A, et al. Intracoronary radiationtherapy improves the clinical and angiographic outcomes of dif-fuse in-stent restenotic lesions: result of the Washington Radiationfor in-stent restenosis trial for long lesions (long WRIST) studies.Circulation 2003;107:1044–1749.

12. Waksman R, Adjani A, White R, et al. Intravascular gammaradiation for in-stent restenosis in saphenous-vein bypass grafts.N Engl J Med 2002;346:1194–1199.

490 Bonan