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Quantitative analysis of coronary artery restenosis after coronary angioplasty—Has the rose lost its bloom?
)ACC V91, R No . 5
946
April 1992 :946-7
Editorial Comment
Quantitative Analysis of Coronary Artery Restenosis After Coronary Angioplasty--Has the Rose Lost Its Bloom?" K . LANCE GOULD, MD, FACC Aousrun,
Texas
Present study. At first glance, the study by Rensing et al . (I) in this issue of the Journal appears to be a dry statistical report on the gaussian distribution of measurements of percent diameter stenosis and minimal lumen diameter in patients undergoing angioplasty for coronary artery disease . However, the data in this study lead to some surprising implications of potential major scientific and medical importance. Using objective measurements on coronary arteriugrams before, immediately aferand 6 months aflereoronary angioplasty, Reusing et al . demonstrated the following : subjected I . Ninety percent of all coronary artery stenoses to angioplasty have <74% diameter narrowing ; more severe lesions are uncommon because the pressure gradient across the stenosis required to maintain flow at rest is beyond the physiologic range and therefore rest flow decreases with thrombetic occlusion . 2 . The mean severity of coronary artery narrowing in patients undergoing angioplasty is only 61% diameter stern . sis . 3 . The average absolute minimal lumen diameter observed 6 months after coronary angoplasty is only 0 .47 mm larger than that before angioplasty . The improvement in percent stenosis 6 months after angioplasty is only 16% diameter stenosis units with a mean severity of 61 % diameter stenosis before angioplasty decreasing to 44% diameter stenosis 6 months after angioplasty. 4 . Restenosis after coronary angioplasty dues not occur in an unusual or selected subgroup of patients al risk but occurs in all patients, and therefore probably represents a fundamental heating or scarring process that is a limitation inherent to the procedure itself, not associated with a special group of patients at inherent risk .
"Fditadats published in Jrusrnat rfiso Ameriraa College of Coraialogr seRed the
views ofthe cotta,,, tad & .a uucussaray represent the views of
JACC or From
the American Cotese of Cardiology the Division of Cardiology and Posilror. Diagnoslie and Research Center, DepNancnt ar Medicine . University of Texas Medical school al Houston. Houston . Texas . This study was based on wortsupponed In pan by Grants R91-HL2a852 . HL26hs5 and 1-11-25356f-the Nulioml ls,litutes of Health, ac[hesda, Maryland . A tar-av reeednnt~, K. Loner Guard . MD. Rmm 4.250 MSMB . University ofTexas Medical School at Houston, Houston, Texas 77a!a. 01932 by 16, A .-n- Culls ofC-dblnpy
This extensive study by Reusing et al- (1) demonstrates the importance of objectively measuring the severity of coronary artery stenosis and its application to the problem of restenosis after coronary angioplasty. Their observation that the diameter narrowing of most coronary artery stenoses is <75% fits with our series of studies on the fluid dynamic behavior of such stenoses (2-4) . Their study also definitively confirms our report that, with use of automated quantitative coronary arleriographic analysis (5), the average percent diamctcr stenosis is 68% before and 49% after angioplasty for an actual improvement of only 1911' diameter stenosis units, comparable to the l6% improvement reported by Rensing et al. (1). The change in minimal lumen diameter was +0 .6 mm by our calibrated analysis, comparable to the 0.47 mm reported by Rensing et al . Selection of patients for coronary angloplasty . In our study (5) visually estimated percent diameter stenosis by experienced invasive cardiologists was 85% before and 30% after angoplasty . an improvement of 55% diameter stenosis units. 'lhrus, experienced interventionaf cardiologists visu . ally overestimated severity of stenoses >50% and underestimated those of milder severity (<50%) (5) . A visually estimated improvement of 55% diameter stenosis units versus an objectively measured improvement of 19% involves an error of (55% - 19%%))l9% or 189% . Most invasive cardiologists would not tolerate explicit, known errors of 189% in their estimates, yet they routinely make major decisions based on such imprecise methods . Nor would they claim to judge 0 .5-mm changes visually, yet in fact do so regularly . Because coronary flow and flow reserve depend on lumen diameter raised to the fourth power, these small dimensional changes, which cannot be visually estimated, have major effects on coronary flow reserve . A 60% diameter stenosis restricts coronary flow only minimally experimentally (2-4). Furthermore, even if measured accurately, percent diameter stenosis alone correlates poorly with directly measured flow reserve (2-4). However, integrated geometric analysis including absolute lumen area, percent narrowing and lengthlshape effects correlates well with directly measured flow reserve, thereby providing a rational conceptual framework for assessing stenosis severity (2-4) . Yet patient selection for coronary angioplasty is not commonly based en objective measures of stenosis severity. It is somewhat unsettling that the average visually estimated 85% diameter stenosis before coronary angioplasty, as commonly reported in all clinical laboratories, is rarely actually present in our data or those of Rensing et al . because it is physiologically improbable on theoretic, experimental and clinical grounds. Tolerance of such imprecision combined with a geometric increase in coronary arteriogra. phyiangioplasty (having a doubling time of 4 to 5 yeas 121) despite the ability to control most angina with medical therapy raises real questions . Has the entire cardiology profession ascribed to measurements for patient selection and a,35.1U9719Vt5.m
COULD
19, No. 5 April 199:946-s JACC V .I.
assessment of results of coronary an gioplasty that are scientifically, untenable? Benefits of enranary angioplasly . If one asked a committee of interventionalisls, noninvasive cardiologists, cardiovascular scientists, third party payers and patients whether the current effort and expense of coronary angioplasty is worth a mean improvement of 0 .47-mm lumen diameter and 16% diameter stenosis units, grave reservations would probably arise . If this question were further expanded to explain carefully that all stenoscs resrennse after angioplasty as a part of the inherent healing process, with approximately 25 exceeding whatever arbitrary cutoff point one chooses on a bell-shaped curve of restenosis, further grave reservations would arise . A skeptic might point out that angioplasty replaces coronary artery stenosis due to atherosclerosis with a stenosis due to reparative fibrous prolifertrtion . It is interesting to compare these changes with those observed after intense dietary management, as published in our randomized . arteriographically controlled trial (6) in which percent diameter stenosis after a strict low fat diet changed from 66% to 57% in the group with stenosis severity comparable to that of the patients of Reusing et al . (1) . A common criticism of our study is that few people will adhere to such a strict low fat diet . However, in my own practicewithin the framework of routine clinical visits without special cooks, group therapy, support teams orfree food-most of my patients adhere to such a diet, as judged by marked weight loss and cholesterol lowering, providing I spend the time to explain the angiographic data, ways to make the diet work and the eltec :iveness and importance of dietary and drug management. Brown et al . (7) demonstrated similar regression with use of cholesterol-lowering drugs and a 73% decrease in clinical events of death and myocardial infarction and need for angioplasty or coronary bypass surgery in the treated versus the control group . Finally, it is estimated that nationally only 17% of patients undergoing coronary angioplasty or bypass surgery are offered serious risk factor modification including cholesterol-lowering drugs to prevent regression of disease in other arteries. Given the effectiveness of strict risk factor ml cation including the use of cholesterol-lowering drugs (610), one might raise questions as to whether 60% diameter stenases, which only moderately impair coronary flow reserve, might also be treated with strict risk factor modification in addition to or, in many instances, instead of mechanical intervention. The role of endothelial-plalelet interaction
947
EPtIORIAL COMMENT in causing angina or unstable coronary syndromes, or both, is now recognized. Vigorous risk factor modification alters these interactions in uncertain ways to markedly reduce angina and acute events in controlled randomized trials (6-106 Conclusions, These observations raise the question whether cardiology has focused too much on doing coronary angioplasty preeedures rather than on addressing-he needs it, by what criteria and what the results are . Is angioplasty being done for cardiologists or for patients? These issues require that cardiologists define more thoughtfully who needs coronary angioplasty by objective criteria, measure what the effects are and make strict risk factor modification a serious addendum or alternative to interventional procedures .
References
t . Rcairg RJ. 0000055 WRM. Deckers JW, de peyter P1. Tiiuen 1GP . Struts PW. Lumen nanowirgaf er prrculaneas lrmtdmmnaltoronary banoon arlpjoplauy sm!nw s a sear pussies distribution : a gmeilat n 2.
3.
aneiogmphic study in 1 .445 wcecsshrtydiatedlesens I Am Col Cudkd 1992;19:939-45Gould KL. Coronary Artery SRSOSis, a Textbook of Corwwry Parhephyaiok,gy . Quenlilat,or A,Rriorrepky. Cardiac PEP and Rewrsd of
Coronary Artery Disease . New York ; Else•ier Science Patrtsbtag,1958. Could KL. Positron enissiott romogrophy too heel disease : oliniw update . In: know-old E . m . Heart 0050x, A Textlmoh of Cardiaras-
4.
cular Medicine. 3rd. ed. 10th update- Hriladcrplda : We Saonders, 1990. Gouts KL. Identilyirg awd -mg -61y of coronary artery steno-
5.
sis: quantitative coronary aneriography and positron endssar rorootaaphy . Circulation 19880 :237-45 . Fleming RM. Kirkeeide RL. smaaug RW, Gould KL. 3'Yons m visual inrerpretatine of coronary auteriopantru a detected by gwARanve rosy-
nary anenogmply. J Am Coll Cordial 1991',15 :?15-51 A.
oro ob
ON.
schervdn LW . Bream SE, et at . Can IVestyle changes
reverse alherosckrosis? Lancet 1990 -,33&129-337. Brown GB. Alters JJ . Esher LD, et at Niacin m ki atam, etmtsned with eokdipm rcpesves edronary nthuosek:msis and prevents clinical vents m men with elevated apoipoprolein R . N Ergl J Med 1990}23: 1389-98 . S. Cashimlemphili L, Mack WJ, Pooeda 3M. Sanmarco ME, Azrn SP, Blankenhom DH . Boafical eB'ats nr ca!c5 !-tiuie on cnmnarv uherexkross . JANA 1990;26fttO13a .
9. Kaae JP . Malloy MJ. Pros TA. Philips NIL Diets IC, Hovel Rl . Aegremen of coronary athemukrosis dining treatment of fonfl d 1y perehole5lerokniawirhemntneddtugng roer .JAMA1990264:300710,
12. BudrwaM H, Baron RL, Maths 1P.
V
al. Effect of partial ilea) bypass
surgery on anmlty and morbidity from coronary heat disease in patients with hyperchoksterolasm, a four year follow op. N Engl I Med 1990,323045-55 .
946
April 1992 :946-7
Editorial Comment
Quantitative Analysis of Coronary Artery Restenosis After Coronary Angioplasty--Has the Rose Lost Its Bloom?" K . LANCE GOULD, MD, FACC Aousrun,
Texas
Present study. At first glance, the study by Rensing et al . (I) in this issue of the Journal appears to be a dry statistical report on the gaussian distribution of measurements of percent diameter stenosis and minimal lumen diameter in patients undergoing angioplasty for coronary artery disease . However, the data in this study lead to some surprising implications of potential major scientific and medical importance. Using objective measurements on coronary arteriugrams before, immediately aferand 6 months aflereoronary angioplasty, Reusing et al . demonstrated the following : subjected I . Ninety percent of all coronary artery stenoses to angioplasty have <74% diameter narrowing ; more severe lesions are uncommon because the pressure gradient across the stenosis required to maintain flow at rest is beyond the physiologic range and therefore rest flow decreases with thrombetic occlusion . 2 . The mean severity of coronary artery narrowing in patients undergoing angioplasty is only 61% diameter stern . sis . 3 . The average absolute minimal lumen diameter observed 6 months after coronary angoplasty is only 0 .47 mm larger than that before angioplasty . The improvement in percent stenosis 6 months after angioplasty is only 16% diameter stenosis units with a mean severity of 61 % diameter stenosis before angioplasty decreasing to 44% diameter stenosis 6 months after angioplasty. 4 . Restenosis after coronary angioplasty dues not occur in an unusual or selected subgroup of patients al risk but occurs in all patients, and therefore probably represents a fundamental heating or scarring process that is a limitation inherent to the procedure itself, not associated with a special group of patients at inherent risk .
"Fditadats published in Jrusrnat rfiso Ameriraa College of Coraialogr seRed the
views ofthe cotta,,, tad & .a uucussaray represent the views of
JACC or From
the American Cotese of Cardiology the Division of Cardiology and Posilror. Diagnoslie and Research Center, DepNancnt ar Medicine . University of Texas Medical school al Houston. Houston . Texas . This study was based on wortsupponed In pan by Grants R91-HL2a852 . HL26hs5 and 1-11-25356f-the Nulioml ls,litutes of Health, ac[hesda, Maryland . A tar-av reeednnt~, K. Loner Guard . MD. Rmm 4.250 MSMB . University ofTexas Medical School at Houston, Houston, Texas 77a!a. 01932 by 16, A .-n- Culls ofC-dblnpy
This extensive study by Reusing et al- (1) demonstrates the importance of objectively measuring the severity of coronary artery stenosis and its application to the problem of restenosis after coronary angioplasty. Their observation that the diameter narrowing of most coronary artery stenoses is <75% fits with our series of studies on the fluid dynamic behavior of such stenoses (2-4) . Their study also definitively confirms our report that, with use of automated quantitative coronary arleriographic analysis (5), the average percent diamctcr stenosis is 68% before and 49% after angioplasty for an actual improvement of only 1911' diameter stenosis units, comparable to the l6% improvement reported by Rensing et al. (1). The change in minimal lumen diameter was +0 .6 mm by our calibrated analysis, comparable to the 0.47 mm reported by Rensing et al . Selection of patients for coronary angloplasty . In our study (5) visually estimated percent diameter stenosis by experienced invasive cardiologists was 85% before and 30% after angoplasty . an improvement of 55% diameter stenosis units. 'lhrus, experienced interventionaf cardiologists visu . ally overestimated severity of stenoses >50% and underestimated those of milder severity (<50%) (5) . A visually estimated improvement of 55% diameter stenosis units versus an objectively measured improvement of 19% involves an error of (55% - 19%%))l9% or 189% . Most invasive cardiologists would not tolerate explicit, known errors of 189% in their estimates, yet they routinely make major decisions based on such imprecise methods . Nor would they claim to judge 0 .5-mm changes visually, yet in fact do so regularly . Because coronary flow and flow reserve depend on lumen diameter raised to the fourth power, these small dimensional changes, which cannot be visually estimated, have major effects on coronary flow reserve . A 60% diameter stenosis restricts coronary flow only minimally experimentally (2-4). Furthermore, even if measured accurately, percent diameter stenosis alone correlates poorly with directly measured flow reserve (2-4). However, integrated geometric analysis including absolute lumen area, percent narrowing and lengthlshape effects correlates well with directly measured flow reserve, thereby providing a rational conceptual framework for assessing stenosis severity (2-4) . Yet patient selection for coronary angioplasty is not commonly based en objective measures of stenosis severity. It is somewhat unsettling that the average visually estimated 85% diameter stenosis before coronary angioplasty, as commonly reported in all clinical laboratories, is rarely actually present in our data or those of Rensing et al . because it is physiologically improbable on theoretic, experimental and clinical grounds. Tolerance of such imprecision combined with a geometric increase in coronary arteriogra. phyiangioplasty (having a doubling time of 4 to 5 yeas 121) despite the ability to control most angina with medical therapy raises real questions . Has the entire cardiology profession ascribed to measurements for patient selection and a,35.1U9719Vt5.m
COULD
19, No. 5 April 199:946-s JACC V .I.
assessment of results of coronary an gioplasty that are scientifically, untenable? Benefits of enranary angioplasly . If one asked a committee of interventionalisls, noninvasive cardiologists, cardiovascular scientists, third party payers and patients whether the current effort and expense of coronary angioplasty is worth a mean improvement of 0 .47-mm lumen diameter and 16% diameter stenosis units, grave reservations would probably arise . If this question were further expanded to explain carefully that all stenoscs resrennse after angioplasty as a part of the inherent healing process, with approximately 25 exceeding whatever arbitrary cutoff point one chooses on a bell-shaped curve of restenosis, further grave reservations would arise . A skeptic might point out that angioplasty replaces coronary artery stenosis due to atherosclerosis with a stenosis due to reparative fibrous prolifertrtion . It is interesting to compare these changes with those observed after intense dietary management, as published in our randomized . arteriographically controlled trial (6) in which percent diameter stenosis after a strict low fat diet changed from 66% to 57% in the group with stenosis severity comparable to that of the patients of Reusing et al . (1) . A common criticism of our study is that few people will adhere to such a strict low fat diet . However, in my own practicewithin the framework of routine clinical visits without special cooks, group therapy, support teams orfree food-most of my patients adhere to such a diet, as judged by marked weight loss and cholesterol lowering, providing I spend the time to explain the angiographic data, ways to make the diet work and the eltec :iveness and importance of dietary and drug management. Brown et al . (7) demonstrated similar regression with use of cholesterol-lowering drugs and a 73% decrease in clinical events of death and myocardial infarction and need for angioplasty or coronary bypass surgery in the treated versus the control group . Finally, it is estimated that nationally only 17% of patients undergoing coronary angioplasty or bypass surgery are offered serious risk factor modification including cholesterol-lowering drugs to prevent regression of disease in other arteries. Given the effectiveness of strict risk factor ml cation including the use of cholesterol-lowering drugs (610), one might raise questions as to whether 60% diameter stenases, which only moderately impair coronary flow reserve, might also be treated with strict risk factor modification in addition to or, in many instances, instead of mechanical intervention. The role of endothelial-plalelet interaction
947
EPtIORIAL COMMENT in causing angina or unstable coronary syndromes, or both, is now recognized. Vigorous risk factor modification alters these interactions in uncertain ways to markedly reduce angina and acute events in controlled randomized trials (6-106 Conclusions, These observations raise the question whether cardiology has focused too much on doing coronary angioplasty preeedures rather than on addressing-he needs it, by what criteria and what the results are . Is angioplasty being done for cardiologists or for patients? These issues require that cardiologists define more thoughtfully who needs coronary angioplasty by objective criteria, measure what the effects are and make strict risk factor modification a serious addendum or alternative to interventional procedures .
References
t . Rcairg RJ. 0000055 WRM. Deckers JW, de peyter P1. Tiiuen 1GP . Struts PW. Lumen nanowirgaf er prrculaneas lrmtdmmnaltoronary banoon arlpjoplauy sm!nw s a sear pussies distribution : a gmeilat n 2.
3.
aneiogmphic study in 1 .445 wcecsshrtydiatedlesens I Am Col Cudkd 1992;19:939-45Gould KL. Coronary Artery SRSOSis, a Textbook of Corwwry Parhephyaiok,gy . Quenlilat,or A,Rriorrepky. Cardiac PEP and Rewrsd of
Coronary Artery Disease . New York ; Else•ier Science Patrtsbtag,1958. Could KL. Positron enissiott romogrophy too heel disease : oliniw update . In: know-old E . m . Heart 0050x, A Textlmoh of Cardiaras-
4.
cular Medicine. 3rd. ed. 10th update- Hriladcrplda : We Saonders, 1990. Gouts KL. Identilyirg awd -mg -61y of coronary artery steno-
5.
sis: quantitative coronary aneriography and positron endssar rorootaaphy . Circulation 19880 :237-45 . Fleming RM. Kirkeeide RL. smaaug RW, Gould KL. 3'Yons m visual inrerpretatine of coronary auteriopantru a detected by gwARanve rosy-
nary anenogmply. J Am Coll Cordial 1991',15 :?15-51 A.
oro ob
ON.
schervdn LW . Bream SE, et at . Can IVestyle changes
reverse alherosckrosis? Lancet 1990 -,33&129-337. Brown GB. Alters JJ . Esher LD, et at Niacin m ki atam, etmtsned with eokdipm rcpesves edronary nthuosek:msis and prevents clinical vents m men with elevated apoipoprolein R . N Ergl J Med 1990}23: 1389-98 . S. Cashimlemphili L, Mack WJ, Pooeda 3M. Sanmarco ME, Azrn SP, Blankenhom DH . Boafical eB'ats nr ca!c5 !-tiuie on cnmnarv uherexkross . JANA 1990;26fttO13a .
9. Kaae JP . Malloy MJ. Pros TA. Philips NIL Diets IC, Hovel Rl . Aegremen of coronary athemukrosis dining treatment of fonfl d 1y perehole5lerokniawirhemntneddtugng roer .JAMA1990264:300710,
12. BudrwaM H, Baron RL, Maths 1P.
V
al. Effect of partial ilea) bypass
surgery on anmlty and morbidity from coronary heat disease in patients with hyperchoksterolasm, a four year follow op. N Engl I Med 1990,323045-55 .