- Email: [email protected]
Acute vasculitis after endovascular brachytherapy
144
I. J. Radiation Oncology
255
● Biology ● Physics
Volume 51, Number 3, Supplement 1, 2001
RENO: A European Surveillance Registry of Coronary Brachytherapy with the Novoste™ Beta-Cath™ System
V. Coen1, W. Sauerwein2, R. Orrechia3, P. Von Rottkay4, P. Coucke5, M. Ehnert6, M. Donsbach7, P. Urban8, P. Levendag1 1 Radiation Oncology, University Hospital Rotterdam/Daniel den Hoed Cancer Center, Rotterdam, Netherlands, 2Zentrum fuer Strahlungstherapie, Universitaetsklinikum, Essen, Germany, 3Departement of Medicine, Centro Cuore Columbus, Milan, Italy, 4Mueller Hospital, Munchen, Germany, 5Department of Medicine, C.H.U.V., Lausanne, Switzerland, 6St. Georg Hospital, Hamburg, Germany, 7St. Johannes Hospital, Dortmund, Germany, 8Cardiovascular Department, La Tour Hospital Meyrin, Geneva, Switzerland
Purpose: Intravascular brachytherapy (VBT) has proven to be an effective mode of preventing restenosis following Percutaneous Coronary Intervention (PCI), but there are no data as yet concerning the application of VBT in routine clinical practice. Materials and Methods: Between April 1999 and September 2000, 1036 consecutive patients treated in 47 European centres with the Novoste Beta-Cath™ System were included in RENO, the single available registry of VBT. Results: The 6 months follow-up data have so far been obtained in 546 patients. 785 (76.7%) patients were males, and mean age was 61.9⫾10.2 years. 248 (26.3%) had unstable angina and 238 (23.4%) were diabetics. 1030 (94.1%) target lesions were in native vessels and 65 (5.9%) in a bypass graft. 196 (17.9%) were de novo lesions, 46 (4.2%) restenotic and 850 (77.6%) in-stent restenosis. Mean estimated reference diameter was 3.2⫾0.5mm, and mean estimated lesion length was 19.2⫾12.0 mm. VBT was successful in 1035/1084 lesions (95.5%), and geographical miss occurred in 67 (6.2%). A dose of 18.8⫾3.2 Gy was delivered at 2 mm from the source axis using a source train of 30 mm (182 lesions), 40 mm (869 lesions) or 60 mm (42 lesions). A pullback stepping manoeuvre was used for 167 (15.5%) procedures. The dwell time had to be fractionated due of ischemia for 40 procedures (3.7%). A new stent was implanted in 327 (30%) lesions. In-hospital MACE rate (Major Adverse Cardiac Events) was 20/1036 patients (1.9%). At discharge, aspirin and clopidogrel were usually given for the duration of at least 6 months. At 6 months follow-up MACE rate was 106/546 (19.4%). Angiographic follow-up was available for 412/546 patients (75.4%): non-occlusive restenosis in 16.8% and total occlusion in 5.7% of cases. A combined end-point for late (30-180 days) definite or suspected target vessel closure was reached in 36 (6.6%) patients. At 6-month follow-up, for 96 eligible patients treated with a pullback stepping procedure MACE rate was 32.3%. Angiographic follow-up was performed in 81 of eligible patients (85.3%): restenosis rate was 34.6%, including 12.3% late total occlusions. Conclusion: These data, derived from a large cohort of unselected consecutive patients, suggest that the good results of recent randomised controlled trials can be replicated in routine clinical practice.
256
Acute Vasculitis after Endovascular Brachytherapy
L.F. Fajardo1,2, S.D. Prionas3, G.L. Kaluza4, A.E. Raizner4 1 Pathology Department, Stanford University, Stanford, CA, 2Pathology Service, Veterans Affairs Medical Center, Palo Alto, CA, 3Varian Medical Systems, Palo Alto, CA, 4Division of Cardiology, Baylor University, Houston, TX
Coronary artery angioplasty, with or without stent deployment, relieves myocardial ischemia but is followed by a high rate of re-stenosis. Endovascular radiation (beta or gamma) at the time of angioplasty prevents re-stenosis in a large proportion of vessels in swine (short term) and humans (short and long term). We have found an unexpected lesion in swine exposed to endovascular beta brachytherapy from 32P sources: an acute necrotizing vasculitis in arterioles located in the peri-adventitial tissues of the irradiated coronary arteries, beyond the vasa-vasorum. It is characterized by fibrinoid necrosis of the arteriolar media, often extending into its intima and adventitia, and occasionally associated with leukocytic exudate or thrombosis. The affected vessels measure 50 to 250 m in diameter (average 132 m) and are located 0.38 to 2.05 mm from the intima of the corresponding coronary artery (as determined in section planes perpendicular to the artery). This lesion has only occurred in samples subjected to radiation. There is no association with the effects produced in the main vessel by angioplasty or stenting, including rupture of elastic lamellae, degree of medial loss, fibrinous exudate, hemorrhage, thrombosis or fibrosis. Although occasionally more than one small vessel is affected at a given section plane, there are usually several uninvolved vessels within the same range of distance from the main artery. The prescribed dose to the coronary arteries has been 3500 cGy at a depth of 0.5 mm from the surface of the intima (approximately 2000 cGy at 1 mm). The dose rate has varied from 25 to 275 cGy/second. A special device has centered the radiation source in the lumen of the main vessel. The dose received by the affected arterioles at the site of vasculitis (as calculated in paraffin sections of tissues subjected to formalin fixation at 150 mm/Hg) has varied approximately between 4000 cGy (for those closest to the main vessel) and 600 cGy (for those farthest). In 3 separate experiments the incidence of this acute vasculitis at one month post-radiation has been 51 % (28/55 porcine coronary vessels exposed to 32P). By six months the incidence of acute vasculitis has decreased to 14 % (4/28 irradiated vessels); however at this late stage there is neointimal proliferation and sclerosis in 46 % of these small vessels, often with significant lumenal narrowing. This suggests that the healing phase of the acute vasculitis occurs within a period of months and can result in considerable deficit of local blood flow. Small vessel vasculitis is not limited to the tissues surrounding the coronary arteries; in a separate experiment acute vasculitis has been detected also around porcine iliac arteries exposed to 32P (6/6 irradiated vessels). These observations indicate that endo-arterial brachytherapy using 32P results in vascular effects beyond the adventitia of the target vessel. This necrotizing vasculitis appears to be causally related to radiation, but its mechanism is unclear. It is likely that the same lesion also occurs in humans. To our knowledge it has not been reported until now, either in the experimental models or in the few human specimens examined after angioplasty/brachytherapy.
I. J. Radiation Oncology
255
● Biology ● Physics
Volume 51, Number 3, Supplement 1, 2001
RENO: A European Surveillance Registry of Coronary Brachytherapy with the Novoste™ Beta-Cath™ System
V. Coen1, W. Sauerwein2, R. Orrechia3, P. Von Rottkay4, P. Coucke5, M. Ehnert6, M. Donsbach7, P. Urban8, P. Levendag1 1 Radiation Oncology, University Hospital Rotterdam/Daniel den Hoed Cancer Center, Rotterdam, Netherlands, 2Zentrum fuer Strahlungstherapie, Universitaetsklinikum, Essen, Germany, 3Departement of Medicine, Centro Cuore Columbus, Milan, Italy, 4Mueller Hospital, Munchen, Germany, 5Department of Medicine, C.H.U.V., Lausanne, Switzerland, 6St. Georg Hospital, Hamburg, Germany, 7St. Johannes Hospital, Dortmund, Germany, 8Cardiovascular Department, La Tour Hospital Meyrin, Geneva, Switzerland
Purpose: Intravascular brachytherapy (VBT) has proven to be an effective mode of preventing restenosis following Percutaneous Coronary Intervention (PCI), but there are no data as yet concerning the application of VBT in routine clinical practice. Materials and Methods: Between April 1999 and September 2000, 1036 consecutive patients treated in 47 European centres with the Novoste Beta-Cath™ System were included in RENO, the single available registry of VBT. Results: The 6 months follow-up data have so far been obtained in 546 patients. 785 (76.7%) patients were males, and mean age was 61.9⫾10.2 years. 248 (26.3%) had unstable angina and 238 (23.4%) were diabetics. 1030 (94.1%) target lesions were in native vessels and 65 (5.9%) in a bypass graft. 196 (17.9%) were de novo lesions, 46 (4.2%) restenotic and 850 (77.6%) in-stent restenosis. Mean estimated reference diameter was 3.2⫾0.5mm, and mean estimated lesion length was 19.2⫾12.0 mm. VBT was successful in 1035/1084 lesions (95.5%), and geographical miss occurred in 67 (6.2%). A dose of 18.8⫾3.2 Gy was delivered at 2 mm from the source axis using a source train of 30 mm (182 lesions), 40 mm (869 lesions) or 60 mm (42 lesions). A pullback stepping manoeuvre was used for 167 (15.5%) procedures. The dwell time had to be fractionated due of ischemia for 40 procedures (3.7%). A new stent was implanted in 327 (30%) lesions. In-hospital MACE rate (Major Adverse Cardiac Events) was 20/1036 patients (1.9%). At discharge, aspirin and clopidogrel were usually given for the duration of at least 6 months. At 6 months follow-up MACE rate was 106/546 (19.4%). Angiographic follow-up was available for 412/546 patients (75.4%): non-occlusive restenosis in 16.8% and total occlusion in 5.7% of cases. A combined end-point for late (30-180 days) definite or suspected target vessel closure was reached in 36 (6.6%) patients. At 6-month follow-up, for 96 eligible patients treated with a pullback stepping procedure MACE rate was 32.3%. Angiographic follow-up was performed in 81 of eligible patients (85.3%): restenosis rate was 34.6%, including 12.3% late total occlusions. Conclusion: These data, derived from a large cohort of unselected consecutive patients, suggest that the good results of recent randomised controlled trials can be replicated in routine clinical practice.
256
Acute Vasculitis after Endovascular Brachytherapy
L.F. Fajardo1,2, S.D. Prionas3, G.L. Kaluza4, A.E. Raizner4 1 Pathology Department, Stanford University, Stanford, CA, 2Pathology Service, Veterans Affairs Medical Center, Palo Alto, CA, 3Varian Medical Systems, Palo Alto, CA, 4Division of Cardiology, Baylor University, Houston, TX
Coronary artery angioplasty, with or without stent deployment, relieves myocardial ischemia but is followed by a high rate of re-stenosis. Endovascular radiation (beta or gamma) at the time of angioplasty prevents re-stenosis in a large proportion of vessels in swine (short term) and humans (short and long term). We have found an unexpected lesion in swine exposed to endovascular beta brachytherapy from 32P sources: an acute necrotizing vasculitis in arterioles located in the peri-adventitial tissues of the irradiated coronary arteries, beyond the vasa-vasorum. It is characterized by fibrinoid necrosis of the arteriolar media, often extending into its intima and adventitia, and occasionally associated with leukocytic exudate or thrombosis. The affected vessels measure 50 to 250 m in diameter (average 132 m) and are located 0.38 to 2.05 mm from the intima of the corresponding coronary artery (as determined in section planes perpendicular to the artery). This lesion has only occurred in samples subjected to radiation. There is no association with the effects produced in the main vessel by angioplasty or stenting, including rupture of elastic lamellae, degree of medial loss, fibrinous exudate, hemorrhage, thrombosis or fibrosis. Although occasionally more than one small vessel is affected at a given section plane, there are usually several uninvolved vessels within the same range of distance from the main artery. The prescribed dose to the coronary arteries has been 3500 cGy at a depth of 0.5 mm from the surface of the intima (approximately 2000 cGy at 1 mm). The dose rate has varied from 25 to 275 cGy/second. A special device has centered the radiation source in the lumen of the main vessel. The dose received by the affected arterioles at the site of vasculitis (as calculated in paraffin sections of tissues subjected to formalin fixation at 150 mm/Hg) has varied approximately between 4000 cGy (for those closest to the main vessel) and 600 cGy (for those farthest). In 3 separate experiments the incidence of this acute vasculitis at one month post-radiation has been 51 % (28/55 porcine coronary vessels exposed to 32P). By six months the incidence of acute vasculitis has decreased to 14 % (4/28 irradiated vessels); however at this late stage there is neointimal proliferation and sclerosis in 46 % of these small vessels, often with significant lumenal narrowing. This suggests that the healing phase of the acute vasculitis occurs within a period of months and can result in considerable deficit of local blood flow. Small vessel vasculitis is not limited to the tissues surrounding the coronary arteries; in a separate experiment acute vasculitis has been detected also around porcine iliac arteries exposed to 32P (6/6 irradiated vessels). These observations indicate that endo-arterial brachytherapy using 32P results in vascular effects beyond the adventitia of the target vessel. This necrotizing vasculitis appears to be causally related to radiation, but its mechanism is unclear. It is likely that the same lesion also occurs in humans. To our knowledge it has not been reported until now, either in the experimental models or in the few human specimens examined after angioplasty/brachytherapy.