possibility, since we are unaware of other studies that report the underutilization of thrombolytic therapy in women.4,5However, databasesof trials of thrombolytic therapy should be examined to determine if there are gender differences in the use of thrombolytic therapy. Nevertheless,in this study, women were more often ineligible for thrombolytic therapy and were lessoften treated with thrombolytic agents even though eligible for treatment.
tients aged >75 years. Only I patient >75 years was given thrombolytic therapy. Table II displays the use of these procedures inpatients 17.5 years. Although a higher proportion of men underwent cardiac catheterization, the difference between men and women was not statistically significant. However, 26% of all men received thrombolytic therapy, whereas only 17% of all women did. Hospital mortality was similar in all men and women (13.3 us 14.2%, p = 0.88) and in men and women aged >7.5 (25.2 us 20.3%,p = 0.34). After adjustment for age, hospital mortality in men and women of all ages remained similar.
It is difficult to explain the underutilization of thrombolytic therapy in women. It is possible that eligible women were closer in age to the upper limit of 75 years and thus were considered ineligible. However, eligible men and women not treated within the trial had the same mean age of 62 years. It is also plausible that women were treated less aggressivelyby predominantly male cardiologists.This is unlikely, sincesimilar proportions of men and women underwent cardiac catheterization, coronary angioplasty and bypass surgery. Of course, the differential use of thrombolytic therapy may have been due to chance or to confounding variables. This is a
1. Douglas PS. Gender, cardiology, and optimal medical care. Circulation 1986;74:917-919. 2. CunninghamMA, Lee TH, Cook EF, Brand DA, Rouan GW, WeisbergMC, Goldman L. The effect of gender on the probability of myocardial infarction amongemergencydepartmentpatients with acute chestpain: a report from The Multicenter Chest Pain Study Group. J Gen Infern Med 1989;4:392-398. 3. Althouse R, Maynard C, Cerqueira MD, Olsutlm M, Ritchie JL, KennedyJW. The Western Washingtonmyocardial infarction registry and emergencydepartment tissue plasminogen activator treatment trial. Am J Cardiol 1990;66: 1298-1303. 4. Lee TH, WeisbergMC, Brand DA, Rouan GW, Goldman L. Candidatesfor thrombolysisamongemergencyroom patients with acute cheatpain. Ann Intern Med 1989;110:957-962. 5. Karlson BW, Herlitz J, EdvardssonN, EmanuelssonH, Sjolin M, Hjalmarson A. Eligibility for intravenousthrombolysisin suspectedacute myocardial infarction. Circularion 1990;82:1140-1146.
Effects of Luminal Eccentricity on Spontaneous Coronary Vasoconstriction After Successful Percutaneous Transluminal Coronary Angioplasty Tim A. Fischell, MD, and Kurt N. Bausback, MD ver the past severalyearsthere hasbeenincreasing recognition that spontaneouscoronary artery vasoconstriction,or spasm,can occur in the dilated coronary segmentafter percutaneoustransluminal coronary angioplasty (PTCA). This vasoconstriction after PTCA has been quantitated in clinical studies,‘v2 and has been well describedin clinical seriesand in case reports.3-6Although the etiology of vasoconstrictionafter PTCA is not fully understood, several mechanisms have been postulated, including the releaseof vasoactive substancesfrom aggregatingplatelets at the site of endothelial injury and the release of endothelium-derived constricting factor(s) after balloon trauma.7 Coronary spasmhas been demonstratedto be one possiblemechanism of acute vessel closure after successfulPTCA.5y6 Furthermore, clinical studieshavesuggesteda significant correlation betweenspontaneousor provokedvasospasm
0
in the dilated coronary segmentwith increasedrestenosis rates after PTCA.8 It hasbeendemonstratedthat lesioneccentricity may be a risk factor for acute coronary closure after PTCA.9 The observationsthat eccentriclesionsmay have a greater potential for dynamic changesin caliber in responseto vasoactivestimuli1ohasled to speculationthat vasospasm may be more pronouncedafter PTCA in eccentric compared with concentric lesions,leading to a greater incidence of acute closure, and possibly late restenosis.l l,i2 This study was designedto examine whether there is any relationship betweenangiographically determined lesion eccentricity and the severityof spontaneousvasoconstriction early after PTCA in the dilated coronary segment.
Sixteen patients scheduled for elective 1 -vessel PTCA of focal stenoses were prospectively entered into the study after informed consent for both PTCA and the study was obtained. Three of these 16patients From the Division of Cardiovascular Medicine, Stanford University had been entered into a previously reported study’ of Medical Center, 300 Pasteur Drive, Stanford, California 94305.This report was supportedin part by a Clinical Investigator Award (T.A.F.), vasomotion after PTCA. Exclusion criteria included and grant 1 KO8 HL-02001-01 from the National Institutes of Health, Bethesda, Maryland. Manuscript received March 25, 1991; revised concurrent nitroglycerin therapy, recent myocardial infarction ( 10 mm, requirement for intracoronary nitroglycerin tions performed as neededuntil the coronary stenosis during PTCA, and technically inadequate coronary had been dilated adequately using angiographic or hemodynamic criteria, or both. arteriography. As soon as was feasible after the final balloon All patients took their usual oral medications ininflation (average 3 minutes; range 2 to 5 minutes), cluding aspirin and calcium antagonists on the day of the balloon catheter and guidewire were withdrawn the procedure. Selective coronary arteriography of the vessel to be dilated was performed in multiple projec- and selective coronary arteriography, in the previoustions, including at least I pair of orthogonal views ly selectedprojection wasperformed. This angiogram using Omnipaque@contrast at a tine rate of 30frames was designated ‘post-PTCA.” The coronary guiding catheter was replaced with an 8Fr right or left coroper second. Coronary angioplasty was performed using either nary artery Judkins “marker” catheter, to be used as an over-the-wire balloon catheter system (14patients) a referencefor coronary quantitation. Coronary arteor a$xed wire balloon catheter system (2 patients). riograms (same projection) were repeated at 15 and Balloon sizes were chosen to approximate the diame- 5’0minutes after thefinal balloon inflation, and again ter of the “normal” coronary segment adjacent to the 3 minutes after the administration of 300 pg of intrasegment to be dilated. At least 2 balloon inflations coronary nitroglycerin given immediately after the were performed in each case, with additional infla- 30-minute angiogram (ce., 33 minutes after thefina !I
1
FIGURE 1. Diagram of S-mm coronary artery segments analyzed by quantitative coronary arteriography in the left (panel A) and right (pane/B) coronary arteries. Segment 1 (angiepkty segment) was defined as the S-mm-long segmeirR centered in the narrowest point of the coronary stenosis to be dilated; segment 2 (control segment, left coronary artery only) was deftned as a segmentintheleft coronary artery not manipulated by the guidewire or balloon catheter. LAD = left anterior descending artery; DIM = obtuse marginal branch; RCA = right coronary artery. FIGURE 2. Detbdi of lesion eccentricity. A cineangiographii frame from the view showing the stenosis at its most severe narrowing and ecce&ic morphology is traced. A centerline is drawn for the normal w lumen, and “b” is designated as ti angiographii radius of the nomd vessel. A second centerline is drawn for the stenotic (lesion) lumen, with “a” being ths perpendiir distance from this cent4ine to the adjacent normal vessel wall. lf the ratio a/b is 10.5, ths lesion is defined as eccentric. In this example a/b = 0.43.
e/b 5 0.5 q Eccentric e/b > 0.5 = Concentric
1 BRIEF REPORTS 531
TABLE
I Patient
and Prbcedural
Data
TABLE Ii Coronary Artery Diameters (minimum in mm): Angioplasty Segment (segment 1)
Lesions Pt. Group
Concentric
Eccentric
Pt. No.
No. of patients 8 8 61 k2 58 f 3 Age (mean years) Men/women 8/O 7/l Coronary dilated 3 LAD, 3 Cx, 2 RCA 4 LAD, 2 Cx, 2 RCA 712 3 % stenosis 66 -+ 3 0.81 k 0.15 Lesion eccentricity (a/b) 0.43 f 0.08* Lesion (min.) diameter (mm) 0.92 f 0.09 0.83 f 0.12 1.85 f 0.21 Final (min.) diameter (mm) 2.02 f 0.24 2.6 Balloon size (mean) (mm) 2.8 3.6 No. of inflations (mean) 4.0 7.1 Max. inflation p&sure 7.2 (mean atm) *p < 0.01 for eccentric versus;oncentric lesion groups. Values,& mean k standard error of the mean. Cx = left circumflex coronary artery; LAD = left anterior descendingcoronary artery; Max. = maximal; min. = minimal: RCA = right coronary artwy.
balloori inflation). AlljZms were analyzed by quantitative arteriographic techniques as previously described.132The resolution of this system has been demonstrated to be f 0.06 mm. Two coronary segments were analyzed in patients undergoing PTCA in the left coronary artery system, Figure 1A. For the 4 patients undergoing right coronary artery PTCA, only segment 1 was analyzed since there was no equivalent ‘Control” segment (Figure IB). One of the 2 designated film readers analyzed the mean and minimal segmental didmeters in each of 3 consecutive end-diastolic frames for each 5-mm-long segment, at each time/condition. The final segmental vessel diameter (mean and mitiimum) at each time was defined as the mean of the 3 end-diastolic measurements.
Post-FTCA
15 Minutes
Pre-PTCA
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUklE
30 Min
After IC NTG
0.99
1.87
1.21
1.26
1.04 1.25 0.97 0.88 0.91 0.76 0.61
1.79 2.56 1.76 1.28 1.99 1.92 1.63
1.61 2.08 1.38 1.09 1.62 1.55 0.96
1.40 1.95 1.40 1.11 1.41 1.57 0.76
1.90 1.85 2.51 1.84 1.37 1.90 1.68 1.44
1.51 1.24 1.48 2.07 1.62 1.57 1.37 0.81
2.26 1.80 2.35 2.56 2.07 2.41 1.81 1.07
Patients with Eccentric Lesion
0.77 1.01 1.18 0.74 0.80 0.52 1.12 0.53
1
2 3 4 5 6 7 8
2.20 1.73 2.02 2.62 2.14 2.13 2.21 1.07
1.73 1.30 1.30 1.94 1.83 1.59 1.58 0.91
After IC NTG = angiogram obtained 3 minutes after 300~ of intracoronary nitroglycerin (33 mintib?s after final balloon inflation); Post-PTCA = angiogram obtained 2 to 5 minutes after final balloon inflation, guidewire removed; Pre-PTCA = angiographybefore crossing lesion; 15 Min = angiogram 15 minutes afterfinal balloon inflation; 30 Min =angiogram 30 minutes afterfinal inflation.
For the purposes of defining lesion eccentricity, a coronary lesion was defined as eccentric if the luminal center line at the narrowest point of the stenosis was in the outer 25% of the adjacent normal lumen (Figure 2). For purposes of determining percent vasoconstriction, the vessel diameters measured from the angiogram after intracoronary nitroglycerin (NTG) were defined as the maximally vakodilated state so that: % vasoconstriction (t> = diameter after NTG - diameter at time t f diameter after NTG.
30 Minutes
68
15 Min
Patients with Concentric Lesion
ihe
532
Post-PTCA
AUGUST
15, 1991
FIGURE 3. Bar graph showing the spontanews vaskonstrictor responserr after percuthneeus transluminel ceromwy angioz WCA) fp 810 ansioplaety segment comxntnc(n=S)andeccehic (n = 8) leded subgroups, and iti the contrel se&nent (n = 12) Wing the fir4 30 minutes aft& PTCA. Vertical bar?, percent imtiownstriction (mean f standard enur of the mean) for each segment, defined as the percent &a&e in minimal seginental vessel dlalmeter at each the compared wltb the dim* 3 minutes after the administration of 300 a of intracerondry nltroglycedn (IC NTG). There was 110signitic&tdWrenceinthedeg~ofvaqconstrictienbetweehtheconceWkati W mtiiopb* se&mwb at WY the poht. V~strietion in the angiolih!stywgmwt(conoeirtricandoccwtrlc) was SIgnigroator than mat observ~inthecentreleegmentatl5and 30 minutek after PTCA (*p
tients aged >75 years. Only I patient >75 years was given thrombolytic therapy. Table II displays the use of these procedures inpatients 17.5 years. Although a higher proportion of men underwent cardiac catheterization, the difference between men and women was not statistically significant. However, 26% of all men received thrombolytic therapy, whereas only 17% of all women did. Hospital mortality was similar in all men and women (13.3 us 14.2%, p = 0.88) and in men and women aged >7.5 (25.2 us 20.3%,p = 0.34). After adjustment for age, hospital mortality in men and women of all ages remained similar.
It is difficult to explain the underutilization of thrombolytic therapy in women. It is possible that eligible women were closer in age to the upper limit of 75 years and thus were considered ineligible. However, eligible men and women not treated within the trial had the same mean age of 62 years. It is also plausible that women were treated less aggressivelyby predominantly male cardiologists.This is unlikely, sincesimilar proportions of men and women underwent cardiac catheterization, coronary angioplasty and bypass surgery. Of course, the differential use of thrombolytic therapy may have been due to chance or to confounding variables. This is a
1. Douglas PS. Gender, cardiology, and optimal medical care. Circulation 1986;74:917-919. 2. CunninghamMA, Lee TH, Cook EF, Brand DA, Rouan GW, WeisbergMC, Goldman L. The effect of gender on the probability of myocardial infarction amongemergencydepartmentpatients with acute chestpain: a report from The Multicenter Chest Pain Study Group. J Gen Infern Med 1989;4:392-398. 3. Althouse R, Maynard C, Cerqueira MD, Olsutlm M, Ritchie JL, KennedyJW. The Western Washingtonmyocardial infarction registry and emergencydepartment tissue plasminogen activator treatment trial. Am J Cardiol 1990;66: 1298-1303. 4. Lee TH, WeisbergMC, Brand DA, Rouan GW, Goldman L. Candidatesfor thrombolysisamongemergencyroom patients with acute cheatpain. Ann Intern Med 1989;110:957-962. 5. Karlson BW, Herlitz J, EdvardssonN, EmanuelssonH, Sjolin M, Hjalmarson A. Eligibility for intravenousthrombolysisin suspectedacute myocardial infarction. Circularion 1990;82:1140-1146.
Effects of Luminal Eccentricity on Spontaneous Coronary Vasoconstriction After Successful Percutaneous Transluminal Coronary Angioplasty Tim A. Fischell, MD, and Kurt N. Bausback, MD ver the past severalyearsthere hasbeenincreasing recognition that spontaneouscoronary artery vasoconstriction,or spasm,can occur in the dilated coronary segmentafter percutaneoustransluminal coronary angioplasty (PTCA). This vasoconstriction after PTCA has been quantitated in clinical studies,‘v2 and has been well describedin clinical seriesand in case reports.3-6Although the etiology of vasoconstrictionafter PTCA is not fully understood, several mechanisms have been postulated, including the releaseof vasoactive substancesfrom aggregatingplatelets at the site of endothelial injury and the release of endothelium-derived constricting factor(s) after balloon trauma.7 Coronary spasmhas been demonstratedto be one possiblemechanism of acute vessel closure after successfulPTCA.5y6 Furthermore, clinical studieshavesuggesteda significant correlation betweenspontaneousor provokedvasospasm
0
in the dilated coronary segmentwith increasedrestenosis rates after PTCA.8 It hasbeendemonstratedthat lesioneccentricity may be a risk factor for acute coronary closure after PTCA.9 The observationsthat eccentriclesionsmay have a greater potential for dynamic changesin caliber in responseto vasoactivestimuli1ohasled to speculationthat vasospasm may be more pronouncedafter PTCA in eccentric compared with concentric lesions,leading to a greater incidence of acute closure, and possibly late restenosis.l l,i2 This study was designedto examine whether there is any relationship betweenangiographically determined lesion eccentricity and the severityof spontaneousvasoconstriction early after PTCA in the dilated coronary segment.
Sixteen patients scheduled for elective 1 -vessel PTCA of focal stenoses were prospectively entered into the study after informed consent for both PTCA and the study was obtained. Three of these 16patients From the Division of Cardiovascular Medicine, Stanford University had been entered into a previously reported study’ of Medical Center, 300 Pasteur Drive, Stanford, California 94305.This report was supportedin part by a Clinical Investigator Award (T.A.F.), vasomotion after PTCA. Exclusion criteria included and grant 1 KO8 HL-02001-01 from the National Institutes of Health, Bethesda, Maryland. Manuscript received March 25, 1991; revised concurrent nitroglycerin therapy, recent myocardial infarction ( 10 mm, requirement for intracoronary nitroglycerin tions performed as neededuntil the coronary stenosis during PTCA, and technically inadequate coronary had been dilated adequately using angiographic or hemodynamic criteria, or both. arteriography. As soon as was feasible after the final balloon All patients took their usual oral medications ininflation (average 3 minutes; range 2 to 5 minutes), cluding aspirin and calcium antagonists on the day of the balloon catheter and guidewire were withdrawn the procedure. Selective coronary arteriography of the vessel to be dilated was performed in multiple projec- and selective coronary arteriography, in the previoustions, including at least I pair of orthogonal views ly selectedprojection wasperformed. This angiogram using Omnipaque@contrast at a tine rate of 30frames was designated ‘post-PTCA.” The coronary guiding catheter was replaced with an 8Fr right or left coroper second. Coronary angioplasty was performed using either nary artery Judkins “marker” catheter, to be used as an over-the-wire balloon catheter system (14patients) a referencefor coronary quantitation. Coronary arteor a$xed wire balloon catheter system (2 patients). riograms (same projection) were repeated at 15 and Balloon sizes were chosen to approximate the diame- 5’0minutes after thefinal balloon inflation, and again ter of the “normal” coronary segment adjacent to the 3 minutes after the administration of 300 pg of intrasegment to be dilated. At least 2 balloon inflations coronary nitroglycerin given immediately after the were performed in each case, with additional infla- 30-minute angiogram (ce., 33 minutes after thefina !I
1
FIGURE 1. Diagram of S-mm coronary artery segments analyzed by quantitative coronary arteriography in the left (panel A) and right (pane/B) coronary arteries. Segment 1 (angiepkty segment) was defined as the S-mm-long segmeirR centered in the narrowest point of the coronary stenosis to be dilated; segment 2 (control segment, left coronary artery only) was deftned as a segmentintheleft coronary artery not manipulated by the guidewire or balloon catheter. LAD = left anterior descending artery; DIM = obtuse marginal branch; RCA = right coronary artery. FIGURE 2. Detbdi of lesion eccentricity. A cineangiographii frame from the view showing the stenosis at its most severe narrowing and ecce&ic morphology is traced. A centerline is drawn for the normal w lumen, and “b” is designated as ti angiographii radius of the nomd vessel. A second centerline is drawn for the stenotic (lesion) lumen, with “a” being ths perpendiir distance from this cent4ine to the adjacent normal vessel wall. lf the ratio a/b is 10.5, ths lesion is defined as eccentric. In this example a/b = 0.43.
e/b 5 0.5 q Eccentric e/b > 0.5 = Concentric
1 BRIEF REPORTS 531
TABLE
I Patient
and Prbcedural
Data
TABLE Ii Coronary Artery Diameters (minimum in mm): Angioplasty Segment (segment 1)
Lesions Pt. Group
Concentric
Eccentric
Pt. No.
No. of patients 8 8 61 k2 58 f 3 Age (mean years) Men/women 8/O 7/l Coronary dilated 3 LAD, 3 Cx, 2 RCA 4 LAD, 2 Cx, 2 RCA 712 3 % stenosis 66 -+ 3 0.81 k 0.15 Lesion eccentricity (a/b) 0.43 f 0.08* Lesion (min.) diameter (mm) 0.92 f 0.09 0.83 f 0.12 1.85 f 0.21 Final (min.) diameter (mm) 2.02 f 0.24 2.6 Balloon size (mean) (mm) 2.8 3.6 No. of inflations (mean) 4.0 7.1 Max. inflation p&sure 7.2 (mean atm) *p < 0.01 for eccentric versus;oncentric lesion groups. Values,& mean k standard error of the mean. Cx = left circumflex coronary artery; LAD = left anterior descendingcoronary artery; Max. = maximal; min. = minimal: RCA = right coronary artwy.
balloori inflation). AlljZms were analyzed by quantitative arteriographic techniques as previously described.132The resolution of this system has been demonstrated to be f 0.06 mm. Two coronary segments were analyzed in patients undergoing PTCA in the left coronary artery system, Figure 1A. For the 4 patients undergoing right coronary artery PTCA, only segment 1 was analyzed since there was no equivalent ‘Control” segment (Figure IB). One of the 2 designated film readers analyzed the mean and minimal segmental didmeters in each of 3 consecutive end-diastolic frames for each 5-mm-long segment, at each time/condition. The final segmental vessel diameter (mean and mitiimum) at each time was defined as the mean of the 3 end-diastolic measurements.
Post-FTCA
15 Minutes
Pre-PTCA
THE AMERICAN
JOURNAL
OF CARDIOLOGY
VOLUklE
30 Min
After IC NTG
0.99
1.87
1.21
1.26
1.04 1.25 0.97 0.88 0.91 0.76 0.61
1.79 2.56 1.76 1.28 1.99 1.92 1.63
1.61 2.08 1.38 1.09 1.62 1.55 0.96
1.40 1.95 1.40 1.11 1.41 1.57 0.76
1.90 1.85 2.51 1.84 1.37 1.90 1.68 1.44
1.51 1.24 1.48 2.07 1.62 1.57 1.37 0.81
2.26 1.80 2.35 2.56 2.07 2.41 1.81 1.07
Patients with Eccentric Lesion
0.77 1.01 1.18 0.74 0.80 0.52 1.12 0.53
1
2 3 4 5 6 7 8
2.20 1.73 2.02 2.62 2.14 2.13 2.21 1.07
1.73 1.30 1.30 1.94 1.83 1.59 1.58 0.91
After IC NTG = angiogram obtained 3 minutes after 300~ of intracoronary nitroglycerin (33 mintib?s after final balloon inflation); Post-PTCA = angiogram obtained 2 to 5 minutes after final balloon inflation, guidewire removed; Pre-PTCA = angiographybefore crossing lesion; 15 Min = angiogram 15 minutes afterfinal balloon inflation; 30 Min =angiogram 30 minutes afterfinal inflation.
For the purposes of defining lesion eccentricity, a coronary lesion was defined as eccentric if the luminal center line at the narrowest point of the stenosis was in the outer 25% of the adjacent normal lumen (Figure 2). For purposes of determining percent vasoconstriction, the vessel diameters measured from the angiogram after intracoronary nitroglycerin (NTG) were defined as the maximally vakodilated state so that: % vasoconstriction (t> = diameter after NTG - diameter at time t f diameter after NTG.
30 Minutes
68
15 Min
Patients with Concentric Lesion
ihe
532
Post-PTCA
AUGUST
15, 1991
FIGURE 3. Bar graph showing the spontanews vaskonstrictor responserr after percuthneeus transluminel ceromwy angioz WCA) fp 810 ansioplaety segment comxntnc(n=S)andeccehic (n = 8) leded subgroups, and iti the contrel se&nent (n = 12) Wing the fir4 30 minutes aft& PTCA. Vertical bar?, percent imtiownstriction (mean f standard enur of the mean) for each segment, defined as the percent &a&e in minimal seginental vessel dlalmeter at each the compared wltb the dim* 3 minutes after the administration of 300 a of intracerondry nltroglycedn (IC NTG). There was 110signitic&tdWrenceinthedeg~ofvaqconstrictienbetweehtheconceWkati W mtiiopb* se&mwb at WY the poht. V~strietion in the angiolih!stywgmwt(conoeirtricandoccwtrlc) was SIgnigroator than mat observ~inthecentreleegmentatl5and 30 minutek after PTCA (*p
