- Email: [email protected]
Direct myocardial revascularization and angiogenesis—how many patients might be eligible?
terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries. Arterioscler Thromb Vasc Biol 1998;18:1386 –1392. 10. Mach F, Lovis C, Gaspoz JM, Unger PF, Bouillie M, Urban P, Rutishauser W. C-reactive protein as a marker for acute coronary syndromes. Eur Heart J 1997;18:1897–1902. 11. Toss H, Lindahl B, Siegbahn A, Wallentin L. Prognostic influence of
increased fibrinogen and C-reactive protein levels in unstable coronary artery disease. Circulation 1997;96:4204 – 4210. 12. Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB. Production of C-reactive protein and risk of coronary events in stable and unstable angina: European concerted action on thrombosis and disabilities angina pectoris study group. Lacent 1997;349:462– 466.
Direct Myocardial Revascularization and Angiogenesis—How Many Patients Might be Eligible? Debabrata Mukherjee, MD, Deepak L. Bhatt, MD, Matthew T. Roe, Vasant Patel, MD, and Stephen G. Ellis, MD oronary artery disease is the leading cause of mortality and morbidity in the United States. C Established approaches for treating coronary artery 1
disease include medications that reduce myocardial oxygen demand, medications and lifestyle measures to prevent further disease progression, restoration of blood flow to a localized segment of the epicardial coronary artery using percutaneous coronary intervention (PCI), and bypassing the obstruction entirely using coronary artery bypass grafting (CABG). However, a significant number of patients have diffuse coronary artery disease, absent conduits after bypass surgery, small distal vessels, and comorbidities that may preclude PCI or CABG. As the population continues to age, the proportion of patients ineligible for traditional methods of revascularization may increase. Newer modalities of therapy that are being investigated in these patients include operative and percutaneous transluminal myocardial revascularization (TMR)2,3 and injection of growth factors to promote angiogenesis. Few data are available on the number of patients who may be potential candidates for these newer therapies. This study examines the proportion of patients with coronary artery disease undergoing coronary angiography, who are not candidates for conventional revascularization therapy using PCI or CABG, and more importantly who may be candidates for the new modalities of revascularization. •••
Charts and cineangiograms from consecutive patients with known or suspected coronary artery disease undergoing angiography from 2 January 1998 to 22 May 1998 were reviewed to assess the suitability for TMR, TMR with or without CABG, percutaneous TMR, or drug angiogenesis. Patients undergoing coronary angiography before valvular heart surgery were not included in the analysis. Inclusion criteria derived from ongoing clinical trials (VEGF in Ischemia for Vascular Angiogenesis [VIVA]) included anginal class ⱖ2, ejection fraction ⱖ25%, ischemia ⱖ20% of the left ventricle, no myoFrom the Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio. Dr. Ellis’s address is: Cardiac Catheterization Laboratory, F 25, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195. Email: [email protected]. Manuscript received February 23, 1999; revised manuscript received April 20, 1999, and accepted April 21, 1999.
598
©1999 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 84 September 1, 1999
MD,
cardial infarction for ⱕ3 weeks (no left ventricular thrombus, aortic valve disease for percutaneous TMR; no known cancer, retinopathy for drug angiogenesis), and not being a suitable candidate for PCI or CABG. Reasons for ineligibility for PCI included chronic total occlusion with unfavorable morphologic features (ostial location, long gap segment, major branch at occlusion), multiple restenosis, diffuse disease, and severely degenerated saphenous vein graft; for CABG, reasons for ineligibility were poor targets, no conduits, and severe comorbidities such as very low forced expiratory volume, metastatic cancer, or severely calcified aorta. Eligibility for CABG, PCI, or newer therapies was determined by consensus among the reviewers in consultation with a senior angiographer. Patients were divided into Cleveland Clinic Foundation patients and Kaiser Health Maintainenance Organization patients, although both underwent procedures in the same catheterization facility. The secondary objectives were to determine the proportion of patients eligible for individual methods of revascularization and to characterize patients eligible for these modalities. For assessing the amount of myocardial ischemia, left ventricular myocardium was divided into 24 segments (4% of left ventricle per segment) for nuclear studies,4 and into 16 segments for echocardiographic studies (6% of left ventricle per segment). The total percentage of ischemic left ventricle was calculated by adding the total number of ischemic segments and multiplying by 4 for nuclear studies, and 6 for echocardiographic stress studies. Continuous variables are expressed as mean ⫾ SD, and when skewed expressed as median ⫾ quartile. Categorical variables are expressed as percentages. Groups were compared using paired t tests for continuous variables, and multiple logistic regression to analyze independent correlates of candidacy. Statistical analysis was done using Systat 7.0 for Windows, SPSS Inc. 1997 (standard version) (Chicago, Illinois). Baseline characteristics of the 500 patients (415 Cleveland Clinic patients and 85 HMO patients) are listed in Table I. Fifty-nine patients (⬃12%) with symptomatic coronary artery disease out of 500 patients were considered not suitable for PCI or CABG. Table II lists the reasons for their unsuitability. Of the 0002-9149/99/$–see front matter PII S0002-9149(99)00387-2
TABLE I Baseline Characteristics of Patient Population Studied CCF (n ⫽ 415) Age (yrs) Men Smokers (current) Non–insulin-dependent diabetes mellitus Insulin-dependent diabetes mellitus Systemic hypertension Hypercholesterolemia* Chronic renal insufficiency† Class I–II angina Class III–IV angina Ejection fraction No significant disease 1-vessel disease 2-vessel disease 3-vessel disease No. of coronary arteries with ⬎50% narrowing PCI as initial therapy CABG as initial therapy Medicines as initial therapy Nitrate use -blocker use Calcium antagonist use ACE inhibitor use Prior coronary bypass Prior percutaneous coronary intervention
63.6 ⫾ 10 70.8% 12.7% 17.1% 6.0%
HMO (n ⫽ 85) 62 ⫾ 11 58.8% 16.4% 29.4% 5.8%
64.0% 75.1% 2.8% 46.0% 45.7% 60 ⫾ 12 14.4% 23.6% 22.8% 39.1% 1.87 ⫾ 1.09
67.0% 63.5% 2.3% 28.2% 64.7% 60 ⫾ 15 11.7% 27.1% 29.4% 31.7% 1.81 ⫾ 1.02
37.8% 17.3% 44.8% 58.5% 47.4% 32.5% 23.8% 31.1% 33.7%
58.8% 11.7% 29.4% 63.5% 56.4% 17.6% 15.2% 15.2% 14.1%
*Total cholesterol ⬎200 mg/dl, or LDL cholesterol ⬎130 mg/dl, or receiving cholesterol-lowering treatment. † Defined as creatinine ⬎2.0. ACE ⫽ angiotensin-converting enzyme inhibitor; CCF ⫽ Cleveland Clinic Foundation.
TABLE II Reason Patients Were not Considered Suitable for PCI or CABG Chronic total occlusion: 38/59 (64.4%) Poor target: 44/59 (74.5%) Multiple restenosis: 1/59 (1.6%) Degenerated saphenous vein graft: 14/59 (23.7%) No conduit: 3/59 (5.0%) Comorbidities: 2/59 (severe calcified aorta 1, severe COPD 1) 3.3% COPD ⫽ chronic obstructive pulmonary disease.
500 patients, 21 (4.2%; 95% confidence interval [CI] 2.3 to 6.6) were deemed eligible for newer methods of revascularization (2.2% for operative TMR, 3.4% for percutaneous TMR, 1% for operative TMR ⫹ CABG, 3.8% for drug angiogenesis). The eligibility for different modalities was not mutually exclusive. More liberal inclusion criteria (i.e., ejection fraction ⱕ25%, presence of ischemia in ⱕ20% of left ventricle with angina class ⱕ2, absent imaging stress test but a significant amount of viable jeopardized myocardium on ventriculography) identified 59 (11.6%; 95% CI 8.7 to 15.3) eligible patients (4.8% for operative TMR, 10.8% for percutaneous TMR, 2% for TMR ⫹ CABG, 11.6% for drug angiogenesis). There were 85 HMO patients in the study of whom 2.3% (95% CI
TABLE III Characteristics of Patients Eligible for Newer Methods of Revascularization Variables Age (yrs) Men Smokers NIDDM IDDM Hypertension Hypercholesterolemia Prior CABG Prior PTCA Chronic renal insufficiency Ejection fraction No. of diseased vessels
Mean Value or Percent Eligible
p Value
62.5 ⫾ 10 81.0% 28.5% 14.2% 14.2% 76% 81% 76.2% 33.3% 9.5% 42.8 ⫾ 9.00 2.86 ⫾ 0.36
0.737 0.174 0.373 0.736 0.291 0.234 0.415 ⬍0.0001 0.787 ⬍0.05 ⬍0.01 ⬍0.01
The p value is based on paired t test comparison between the eligible group and the entire group (univariate analysis). IDDM ⫽ insulin-dependent diabetes mellitus; NIDDM ⫽ non–insulin-dependent diabetes mellitus.
TABLE IV Independent Correlates of Candidacy for New Methods of Revascularization Using Multivariate Logistic Regression Analysis Parameter Prior coronary bypass Number of coronary arteries with ⬎50% narrowing Ejection fraction †
Odds Ratio
95% CI
5.83 2.37
(2.59–13.65)* (1.38–4.37)†
0.97
(0.94–0.99)‡
‡
*p ⫽ 0.001; p ⫽ 0.01; p ⫽ 0.044.
0.07 to 8.98) were eligible for therapy using the stringent criteria, and 7% were eligible using the liberal criteria, whereas the incidences in tertiary referral population were 4.2% and 11.6%, respectively. Characteristics of patients eligible for newer modes of revascularization are listed in Table III. The independent correlates of candidacy for new methods of revascularization using multivariate logistic regression analysis were previous CABG, lower left ventricular ejection fraction, and number of vessels involved (Table IV). •••
Preliminary small clinical trials of operative TMR have indicated a significant reduction in angina severity, an improved quality of life, decreased mortality, and improved myocardial perfusion in refractory ischemic syndromes.5–7 Percutaneous TMR uses a laser delivered through a novel catheter system, and preliminary results of percutaneous TMR appear promising.4 The ability of angiogenic factors to induce formation of collateral circulation has been demonstrated in a rabbit ischemic leg model,8 and in human peripheral vascular disease.9,10 Our data shows that an important proportion (⬃12%) of patients with symptomatic obstructive coronary artery disease with documented ischemia, who undergo coronary angiography at tertiary referral centers, are not candidates for PCI or CABG. With use of criteria that includes ejection fraction ⱖ25%, docuBRIEF REPORTS
599
mented ischemia in ⱖ20% of the left ventricle, and angina class ⱖ2, approximately 5% of patients would be eligible for newer methods of therapy. The criteria were based on the most rigorous of the Food and Drug Administration–approved current operative TMR, percutaneous TMR, and drug angiogenesis protocols. A larger proportion of patients may be eligible with reasonable but more liberalized criteria, which does not require ejection fraction ⱖ25% and documented ischemia ⱖ20%. Thus, these newer methods of revascularization have the potential to benefit a significant proportion of patients. Of the HMO patients in our study, a smaller proportion (2.3%) were eligible for newer methods of revascularization using the stringent criteria. The HMO population in our study probably better reflects the typical community patient population, rather than the Cleveland Clinic patient population from a tertiary referral center. Recent estimates indicate that there are 6,750,000 Americans with angina pectoris, and an additional 350,000 new cases occur each year.11 There were 1,713,000 cardiac catheterizations performed in 1996 in the United States.12 Based on our study, 100,000 to 200,000 patients/year may be eligible for new methods of revascularization. Indications for percutaneous TMR, operative TMR, and drug angiogenesis at this point remain uncertain. This is a retrospective chart and angiographic review study of a small population of patients. The patient population studied is a higher than average risk population referred to a tertiary care hospital and may overestimate the proportion of patients eligible for new therapies compared
with the community setting. The percentage eligible seen in the HMO population may be better reflective of community practices. 1. Rosamond WD, Chambless LE, Folsom AR, Cooper LS, Conwill DE, Clegg L, Wang CH, Heiss G. Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994. N Engl J Med 1998;339: 861– 867. 2. Hughes GC, Donovan CL, Lowe JE, Landolfo KP. Combined TMR and mitral valve replacement via left thoracotomy. Ann Thorac Surg 1998;65:1141–1143. 3. Kim CB, Kesten R, Javier M, Hayase M, Walton AS, Billingham ME, Kernoff R, Oesterle SN. Percutaneous method of laser myocardial revascularization. Cathet Cardiovasc Diagn 1997;40:223–228. 4. Go RT, MacIntyre WJ, Cook SA, Neumann DR, Brunken RC, Saha G, Underwood DA, Marwick TH, Chen EQ, King JL, Khandekar S. The incidence of scintigraphically viable and nonviable tissue by rubidium-82 and fluorine–18fluorodeoxyglucose positron emission topographic imaging in patients with prior infarction and left ventricular dysfunction. J Nucl Cardiol 1996;3:96 –104. 5. Frazier OH, Cooley DA, Kadipasaoglu KA, Kindenmeir MH, Pehlivanaglu S, Kolff JW, Wilansky S, Moore WH. Myocardial revascularization with laser. Preliminary findings. Circulation 1995;92(suppl II):II-58 –II-65. 6. Cooley DA, Frazier OH, Kadipasaoglu KA, Kindenmeir MH, Pehlivanaglu S, Kolff JW, Wilansky S, Moore WH. Transmyocardial laser revascularization: clinical experience with twelve month follow-up. J Thorac Cardiovasc Surg 1996;111:791–799. 7. Horvath KA, Mannting F, Cummings N, Shernan SK, Cohn LH. Transmyocardial laser revascularization: operative techniques and clinical results at two years. J Thorac Cardiovasc Surg 1996;111:1047–1053. 8. Takashita S, Zheng LP, Brogi E, Kearney M, Pu LQ, Bunting S, Ferrara N, Symes JF, Isner JM. Therapeutic angiogenesis: a single intraarterial bolus of vascular endothelial growth factor augments revascularization a rabbit ischemic hind limb model. J Clin Invest 1994;93:662– 670. 9. Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Asahara T, Rosenfield K, Razvi S, Walsh K, Symes JF. Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischemic limb. Lancet 1996;348:370 –374. 10. Tsurumi Y, Kearney M, Chen D, Silver M, Takeshita S, Yang J, Symes JF, Isner JM. Treatment of acute limb ischemia by intramuscular injection of vascular endothelial growth factor gene. Circulation 1997;96(suppl II):II-382–II-388. 11. Heart and Stroke Facts: 1996 Statistical Supplement. Dallas, TX: American Heart Association. 12. 1999 Heart and Stroke Statistical Update: 1998 Dallas, TX: American Heart Association.
Early Results of Percutaneous Intervention for Severe Coexisting Carotid and Coronary Artery Disease Nadim Al-Mubarak, MD, Gary S. Roubin, MD, PhD, Ming W. Liu, MD, Larry S. Dean, MD, Camilo R. Gomez, MD, Sriram S. Iyer, MD, and Jiri J. Vitek,
C
arotid and coronary artery occlusive disease frequently coexists as part of the systemic atherosclerotic process.1–3 The management of severe coexisting disease poses a major dilemma. Surgical revascularization of 1 vessel is associated with increased rate of complications from the other.4 –11 Staged and simultaneous surgeries of both vascular territories in these patients have been practiced at the expense of significant morbidity and mortality, mainly from myocarFrom the Department of Medicine, Division of Cardiovascular Diseases, and the Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama; and The Center for Endovascular Intervention, Lenox Hill Hospital, New York, New York. Dr. Roubin’s address is: Center for Endovascular Intervention, The Lenox Hill Hospital, 130 East 77th Street, New York, New York 10021. Manuscript received January 6, 1999; revised manuscript received and accepted April 27, 1999.
600
©1999 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 84 September 1, 1999
MD
dial infarction and/or stroke.4 –11 Percutaneous elective carotid artery stenting has been shown to be effective in treating severe occlusive carotid artery disease and may have its greatest benefit in patients with high preoperative risk.12–16 We report our experience with staged or simultaneous carotid artery stenting and coronary angioplasty in a high-risk population with severe coexisting carotid and coronary artery stenoses. •••
Between September 1994 and June 1998, 379 patients underwent stenting of 424 carotid arteries according to a protocol approved by the institutional review board to investigate the feasibility of the procedure. Of those, 51 (13%) consecutively underwent simultaneous or staged percutaneous coronary intervention for severe coexisting coronary artery disease and represent the study group. 0002-9149/99/$–see front matter PII S0002-9149(99)00388-4
increased fibrinogen and C-reactive protein levels in unstable coronary artery disease. Circulation 1997;96:4204 – 4210. 12. Haverkate F, Thompson SG, Pyke SD, Gallimore JR, Pepys MB. Production of C-reactive protein and risk of coronary events in stable and unstable angina: European concerted action on thrombosis and disabilities angina pectoris study group. Lacent 1997;349:462– 466.
Direct Myocardial Revascularization and Angiogenesis—How Many Patients Might be Eligible? Debabrata Mukherjee, MD, Deepak L. Bhatt, MD, Matthew T. Roe, Vasant Patel, MD, and Stephen G. Ellis, MD oronary artery disease is the leading cause of mortality and morbidity in the United States. C Established approaches for treating coronary artery 1
disease include medications that reduce myocardial oxygen demand, medications and lifestyle measures to prevent further disease progression, restoration of blood flow to a localized segment of the epicardial coronary artery using percutaneous coronary intervention (PCI), and bypassing the obstruction entirely using coronary artery bypass grafting (CABG). However, a significant number of patients have diffuse coronary artery disease, absent conduits after bypass surgery, small distal vessels, and comorbidities that may preclude PCI or CABG. As the population continues to age, the proportion of patients ineligible for traditional methods of revascularization may increase. Newer modalities of therapy that are being investigated in these patients include operative and percutaneous transluminal myocardial revascularization (TMR)2,3 and injection of growth factors to promote angiogenesis. Few data are available on the number of patients who may be potential candidates for these newer therapies. This study examines the proportion of patients with coronary artery disease undergoing coronary angiography, who are not candidates for conventional revascularization therapy using PCI or CABG, and more importantly who may be candidates for the new modalities of revascularization. •••
Charts and cineangiograms from consecutive patients with known or suspected coronary artery disease undergoing angiography from 2 January 1998 to 22 May 1998 were reviewed to assess the suitability for TMR, TMR with or without CABG, percutaneous TMR, or drug angiogenesis. Patients undergoing coronary angiography before valvular heart surgery were not included in the analysis. Inclusion criteria derived from ongoing clinical trials (VEGF in Ischemia for Vascular Angiogenesis [VIVA]) included anginal class ⱖ2, ejection fraction ⱖ25%, ischemia ⱖ20% of the left ventricle, no myoFrom the Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio. Dr. Ellis’s address is: Cardiac Catheterization Laboratory, F 25, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195. Email: [email protected]. Manuscript received February 23, 1999; revised manuscript received April 20, 1999, and accepted April 21, 1999.
598
©1999 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 84 September 1, 1999
MD,
cardial infarction for ⱕ3 weeks (no left ventricular thrombus, aortic valve disease for percutaneous TMR; no known cancer, retinopathy for drug angiogenesis), and not being a suitable candidate for PCI or CABG. Reasons for ineligibility for PCI included chronic total occlusion with unfavorable morphologic features (ostial location, long gap segment, major branch at occlusion), multiple restenosis, diffuse disease, and severely degenerated saphenous vein graft; for CABG, reasons for ineligibility were poor targets, no conduits, and severe comorbidities such as very low forced expiratory volume, metastatic cancer, or severely calcified aorta. Eligibility for CABG, PCI, or newer therapies was determined by consensus among the reviewers in consultation with a senior angiographer. Patients were divided into Cleveland Clinic Foundation patients and Kaiser Health Maintainenance Organization patients, although both underwent procedures in the same catheterization facility. The secondary objectives were to determine the proportion of patients eligible for individual methods of revascularization and to characterize patients eligible for these modalities. For assessing the amount of myocardial ischemia, left ventricular myocardium was divided into 24 segments (4% of left ventricle per segment) for nuclear studies,4 and into 16 segments for echocardiographic studies (6% of left ventricle per segment). The total percentage of ischemic left ventricle was calculated by adding the total number of ischemic segments and multiplying by 4 for nuclear studies, and 6 for echocardiographic stress studies. Continuous variables are expressed as mean ⫾ SD, and when skewed expressed as median ⫾ quartile. Categorical variables are expressed as percentages. Groups were compared using paired t tests for continuous variables, and multiple logistic regression to analyze independent correlates of candidacy. Statistical analysis was done using Systat 7.0 for Windows, SPSS Inc. 1997 (standard version) (Chicago, Illinois). Baseline characteristics of the 500 patients (415 Cleveland Clinic patients and 85 HMO patients) are listed in Table I. Fifty-nine patients (⬃12%) with symptomatic coronary artery disease out of 500 patients were considered not suitable for PCI or CABG. Table II lists the reasons for their unsuitability. Of the 0002-9149/99/$–see front matter PII S0002-9149(99)00387-2
TABLE I Baseline Characteristics of Patient Population Studied CCF (n ⫽ 415) Age (yrs) Men Smokers (current) Non–insulin-dependent diabetes mellitus Insulin-dependent diabetes mellitus Systemic hypertension Hypercholesterolemia* Chronic renal insufficiency† Class I–II angina Class III–IV angina Ejection fraction No significant disease 1-vessel disease 2-vessel disease 3-vessel disease No. of coronary arteries with ⬎50% narrowing PCI as initial therapy CABG as initial therapy Medicines as initial therapy Nitrate use -blocker use Calcium antagonist use ACE inhibitor use Prior coronary bypass Prior percutaneous coronary intervention
63.6 ⫾ 10 70.8% 12.7% 17.1% 6.0%
HMO (n ⫽ 85) 62 ⫾ 11 58.8% 16.4% 29.4% 5.8%
64.0% 75.1% 2.8% 46.0% 45.7% 60 ⫾ 12 14.4% 23.6% 22.8% 39.1% 1.87 ⫾ 1.09
67.0% 63.5% 2.3% 28.2% 64.7% 60 ⫾ 15 11.7% 27.1% 29.4% 31.7% 1.81 ⫾ 1.02
37.8% 17.3% 44.8% 58.5% 47.4% 32.5% 23.8% 31.1% 33.7%
58.8% 11.7% 29.4% 63.5% 56.4% 17.6% 15.2% 15.2% 14.1%
*Total cholesterol ⬎200 mg/dl, or LDL cholesterol ⬎130 mg/dl, or receiving cholesterol-lowering treatment. † Defined as creatinine ⬎2.0. ACE ⫽ angiotensin-converting enzyme inhibitor; CCF ⫽ Cleveland Clinic Foundation.
TABLE II Reason Patients Were not Considered Suitable for PCI or CABG Chronic total occlusion: 38/59 (64.4%) Poor target: 44/59 (74.5%) Multiple restenosis: 1/59 (1.6%) Degenerated saphenous vein graft: 14/59 (23.7%) No conduit: 3/59 (5.0%) Comorbidities: 2/59 (severe calcified aorta 1, severe COPD 1) 3.3% COPD ⫽ chronic obstructive pulmonary disease.
500 patients, 21 (4.2%; 95% confidence interval [CI] 2.3 to 6.6) were deemed eligible for newer methods of revascularization (2.2% for operative TMR, 3.4% for percutaneous TMR, 1% for operative TMR ⫹ CABG, 3.8% for drug angiogenesis). The eligibility for different modalities was not mutually exclusive. More liberal inclusion criteria (i.e., ejection fraction ⱕ25%, presence of ischemia in ⱕ20% of left ventricle with angina class ⱕ2, absent imaging stress test but a significant amount of viable jeopardized myocardium on ventriculography) identified 59 (11.6%; 95% CI 8.7 to 15.3) eligible patients (4.8% for operative TMR, 10.8% for percutaneous TMR, 2% for TMR ⫹ CABG, 11.6% for drug angiogenesis). There were 85 HMO patients in the study of whom 2.3% (95% CI
TABLE III Characteristics of Patients Eligible for Newer Methods of Revascularization Variables Age (yrs) Men Smokers NIDDM IDDM Hypertension Hypercholesterolemia Prior CABG Prior PTCA Chronic renal insufficiency Ejection fraction No. of diseased vessels
Mean Value or Percent Eligible
p Value
62.5 ⫾ 10 81.0% 28.5% 14.2% 14.2% 76% 81% 76.2% 33.3% 9.5% 42.8 ⫾ 9.00 2.86 ⫾ 0.36
0.737 0.174 0.373 0.736 0.291 0.234 0.415 ⬍0.0001 0.787 ⬍0.05 ⬍0.01 ⬍0.01
The p value is based on paired t test comparison between the eligible group and the entire group (univariate analysis). IDDM ⫽ insulin-dependent diabetes mellitus; NIDDM ⫽ non–insulin-dependent diabetes mellitus.
TABLE IV Independent Correlates of Candidacy for New Methods of Revascularization Using Multivariate Logistic Regression Analysis Parameter Prior coronary bypass Number of coronary arteries with ⬎50% narrowing Ejection fraction †
Odds Ratio
95% CI
5.83 2.37
(2.59–13.65)* (1.38–4.37)†
0.97
(0.94–0.99)‡
‡
*p ⫽ 0.001; p ⫽ 0.01; p ⫽ 0.044.
0.07 to 8.98) were eligible for therapy using the stringent criteria, and 7% were eligible using the liberal criteria, whereas the incidences in tertiary referral population were 4.2% and 11.6%, respectively. Characteristics of patients eligible for newer modes of revascularization are listed in Table III. The independent correlates of candidacy for new methods of revascularization using multivariate logistic regression analysis were previous CABG, lower left ventricular ejection fraction, and number of vessels involved (Table IV). •••
Preliminary small clinical trials of operative TMR have indicated a significant reduction in angina severity, an improved quality of life, decreased mortality, and improved myocardial perfusion in refractory ischemic syndromes.5–7 Percutaneous TMR uses a laser delivered through a novel catheter system, and preliminary results of percutaneous TMR appear promising.4 The ability of angiogenic factors to induce formation of collateral circulation has been demonstrated in a rabbit ischemic leg model,8 and in human peripheral vascular disease.9,10 Our data shows that an important proportion (⬃12%) of patients with symptomatic obstructive coronary artery disease with documented ischemia, who undergo coronary angiography at tertiary referral centers, are not candidates for PCI or CABG. With use of criteria that includes ejection fraction ⱖ25%, docuBRIEF REPORTS
599
mented ischemia in ⱖ20% of the left ventricle, and angina class ⱖ2, approximately 5% of patients would be eligible for newer methods of therapy. The criteria were based on the most rigorous of the Food and Drug Administration–approved current operative TMR, percutaneous TMR, and drug angiogenesis protocols. A larger proportion of patients may be eligible with reasonable but more liberalized criteria, which does not require ejection fraction ⱖ25% and documented ischemia ⱖ20%. Thus, these newer methods of revascularization have the potential to benefit a significant proportion of patients. Of the HMO patients in our study, a smaller proportion (2.3%) were eligible for newer methods of revascularization using the stringent criteria. The HMO population in our study probably better reflects the typical community patient population, rather than the Cleveland Clinic patient population from a tertiary referral center. Recent estimates indicate that there are 6,750,000 Americans with angina pectoris, and an additional 350,000 new cases occur each year.11 There were 1,713,000 cardiac catheterizations performed in 1996 in the United States.12 Based on our study, 100,000 to 200,000 patients/year may be eligible for new methods of revascularization. Indications for percutaneous TMR, operative TMR, and drug angiogenesis at this point remain uncertain. This is a retrospective chart and angiographic review study of a small population of patients. The patient population studied is a higher than average risk population referred to a tertiary care hospital and may overestimate the proportion of patients eligible for new therapies compared
with the community setting. The percentage eligible seen in the HMO population may be better reflective of community practices. 1. Rosamond WD, Chambless LE, Folsom AR, Cooper LS, Conwill DE, Clegg L, Wang CH, Heiss G. Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994. N Engl J Med 1998;339: 861– 867. 2. Hughes GC, Donovan CL, Lowe JE, Landolfo KP. Combined TMR and mitral valve replacement via left thoracotomy. Ann Thorac Surg 1998;65:1141–1143. 3. Kim CB, Kesten R, Javier M, Hayase M, Walton AS, Billingham ME, Kernoff R, Oesterle SN. Percutaneous method of laser myocardial revascularization. Cathet Cardiovasc Diagn 1997;40:223–228. 4. Go RT, MacIntyre WJ, Cook SA, Neumann DR, Brunken RC, Saha G, Underwood DA, Marwick TH, Chen EQ, King JL, Khandekar S. The incidence of scintigraphically viable and nonviable tissue by rubidium-82 and fluorine–18fluorodeoxyglucose positron emission topographic imaging in patients with prior infarction and left ventricular dysfunction. J Nucl Cardiol 1996;3:96 –104. 5. Frazier OH, Cooley DA, Kadipasaoglu KA, Kindenmeir MH, Pehlivanaglu S, Kolff JW, Wilansky S, Moore WH. Myocardial revascularization with laser. Preliminary findings. Circulation 1995;92(suppl II):II-58 –II-65. 6. Cooley DA, Frazier OH, Kadipasaoglu KA, Kindenmeir MH, Pehlivanaglu S, Kolff JW, Wilansky S, Moore WH. Transmyocardial laser revascularization: clinical experience with twelve month follow-up. J Thorac Cardiovasc Surg 1996;111:791–799. 7. Horvath KA, Mannting F, Cummings N, Shernan SK, Cohn LH. Transmyocardial laser revascularization: operative techniques and clinical results at two years. J Thorac Cardiovasc Surg 1996;111:1047–1053. 8. Takashita S, Zheng LP, Brogi E, Kearney M, Pu LQ, Bunting S, Ferrara N, Symes JF, Isner JM. Therapeutic angiogenesis: a single intraarterial bolus of vascular endothelial growth factor augments revascularization a rabbit ischemic hind limb model. J Clin Invest 1994;93:662– 670. 9. Isner JM, Pieczek A, Schainfeld R, Blair R, Haley L, Asahara T, Rosenfield K, Razvi S, Walsh K, Symes JF. Clinical evidence of angiogenesis after arterial gene transfer of phVEGF165 in patient with ischemic limb. Lancet 1996;348:370 –374. 10. Tsurumi Y, Kearney M, Chen D, Silver M, Takeshita S, Yang J, Symes JF, Isner JM. Treatment of acute limb ischemia by intramuscular injection of vascular endothelial growth factor gene. Circulation 1997;96(suppl II):II-382–II-388. 11. Heart and Stroke Facts: 1996 Statistical Supplement. Dallas, TX: American Heart Association. 12. 1999 Heart and Stroke Statistical Update: 1998 Dallas, TX: American Heart Association.
Early Results of Percutaneous Intervention for Severe Coexisting Carotid and Coronary Artery Disease Nadim Al-Mubarak, MD, Gary S. Roubin, MD, PhD, Ming W. Liu, MD, Larry S. Dean, MD, Camilo R. Gomez, MD, Sriram S. Iyer, MD, and Jiri J. Vitek,
C
arotid and coronary artery occlusive disease frequently coexists as part of the systemic atherosclerotic process.1–3 The management of severe coexisting disease poses a major dilemma. Surgical revascularization of 1 vessel is associated with increased rate of complications from the other.4 –11 Staged and simultaneous surgeries of both vascular territories in these patients have been practiced at the expense of significant morbidity and mortality, mainly from myocarFrom the Department of Medicine, Division of Cardiovascular Diseases, and the Department of Neurology, The University of Alabama at Birmingham, Birmingham, Alabama; and The Center for Endovascular Intervention, Lenox Hill Hospital, New York, New York. Dr. Roubin’s address is: Center for Endovascular Intervention, The Lenox Hill Hospital, 130 East 77th Street, New York, New York 10021. Manuscript received January 6, 1999; revised manuscript received and accepted April 27, 1999.
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©1999 by Excerpta Medica, Inc. All rights reserved. The American Journal of Cardiology Vol. 84 September 1, 1999
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dial infarction and/or stroke.4 –11 Percutaneous elective carotid artery stenting has been shown to be effective in treating severe occlusive carotid artery disease and may have its greatest benefit in patients with high preoperative risk.12–16 We report our experience with staged or simultaneous carotid artery stenting and coronary angioplasty in a high-risk population with severe coexisting carotid and coronary artery stenoses. •••
Between September 1994 and June 1998, 379 patients underwent stenting of 424 carotid arteries according to a protocol approved by the institutional review board to investigate the feasibility of the procedure. Of those, 51 (13%) consecutively underwent simultaneous or staged percutaneous coronary intervention for severe coexisting coronary artery disease and represent the study group. 0002-9149/99/$–see front matter PII S0002-9149(99)00388-4