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Percutaneous myocardial revascularisation using the holmium-YAG laser is effective for refractory angina
TREATMENT
Percutaneous myocardial revascularisation using the holmium-YAG laser is effective for refractory angina Abstracted from: Whitlow PL, DeMaio SJ, Perin EC et al. One-year results of percutaneous myocardial revascularisation for refractory angina pectoris. Am J Cardiol 2003; 91: 1342^1346.
BACKGROUND Studies have shown percutaneous myocardial revascularisation (PMR) to be e¡ective in the treatment of angina. A number of systems for PMR exist using either single or multiple laser pulses and varying optical ¢bre thickness. OBJECTIVE To compare PMR using a 1mm triple pulsed optical ¢bre holmium-YAG laser with maximal medical therapy for refractory angina pectoris. SETTING Twenty centres in the United States; study concludedJanuary 2000. METHOD Randomised controlled trial. PARTICIPANTS Three hundred and thirty people with refractory Canadian class III or IVangina ineligible for coronary bypass grafting and percutaneous intervention and on a maximal medical programme. Inclusion criteria included angina during exercise stress test or at rest (people unable to complete exercise stress test due to hospitalisation and intravenous nitroglycerin for recurrent rest pain were also included and given a test time of 0); left ventricular ejection fraction X30%; target area wall thickness X9 mm. Exclusion criteria included myocardial infarction in previous 3 weeks; medical comorbidity prohibiting treadmill exercise; signi¢cant aortic stenosis; mechanical aortic valve, and left ventricular thrombus. INTERVENTION Participants either continued to receive their medical treatment alone or medical treatment plus PMR. Participants were treated with
164
Evidence-based Cardiovascular Medicine (2003) 7,164 ^165 doi:10.1016/j.ebcm.2003.08.010
325 mg/day aspirin for 41 day before receiving PMR with a 1mm triple pulsed optical ¢bre holmium-YAG laser. The ischaemic area was covered with between 8 and 30 channels approximately 1 cm apart. Participants continued to take 325 mg/day aspirin inde¢nitely after the procedure. OUTCOMES The primary endpoint was at least a 60 second increase in exercise time (Naughton protocol stress test) at1year. Other main outcomes were improvement in function by X2 functional classes, and quality of life (Duke Activity Status score). MAIN RESULTS PMR was more e¡ective than medication alone for the primary outcome (58% PMR v 33% medication alone; p = 0.001). A signi¢cantly greater proportion of participants who received PMR improved X2 functional classes (55% PMR v 31% medication alone; po0.001). PMR improved quality of life compared with medication alone (improvement on Duke Activity Status score: 10.0 units with PMR v 5.7 units with medication alone; p = 0.005). AUTHORS’ CONCLUSIONS PMR treatment using the holmium-YAG system according to the trial protocol improves exercise capability and quality of life. Sources offunding: Eclipse Surgical Technologies Correspondenceto: PWhitlow, Departmentof Cardiology, F25,The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USAE-mail: [email protected] Abstract provided by Bazian Ltd, London
Commentary Myocardial laser revascularization is a technique for treating symptomatic people with coronary artery disease who cannot be revascularized by PCI or CABGs.Transmyocardial laser revascularization (TMR) is performed surgically with the laser beam applied through an epicardial-into-myocardial approach. Percutaneous myocardial laser revascularization (PMR) is performed with a cardiac catheterization approach utilizing retrograde aortic technique whereby the laser catheter is positioned in the ventricle aiming the beam towards an endocardial-into-myocardial penetration.1 PMR appears to be associated with less morbidity thanTMR. The present study by Whitlow et al describes one year results of a prospective, randomized multicenter trial utilizing a solidstate, pulsed-wave, mid-infrared holmium:YAG laser system for PMR. Noteworthy, the qualifications and the reputation of the study’s investigator are excellent. Nevertheless, serious concerns exist regarding the limitations of myocardial revascularization in general and the study’s methodology and results in particular. The holmium:YAG lasers transmit their beams by an optical fiber2,3 and rely on thermal energy to create myocardial channels with the intent of delivering oxygenated blood into ischemic regions of the myocardium, thereby increasing myocardial perfusion. To date, several mechanisms explaining the action of PMR and TMR have been proposed. These include the open channel hypothesis, the angiogenesis process and sympathetic denervation of the myocardium.There is ample experimental and pathologic documentation refuting either the existence or the attributed beneficial effect of each of the above-mentioned mechanisms. The transmural channels obliterate shortly after the procedure eventually being replaced by scarred tissue.4 Neorevascularization or angiogenesis turned out to be a nonspecific response to tissue injury, which can be obtained by simple needle punctures.5 The notion that denervation accounts for reduction in angina severity has been successfully challenged and could not be supported by animal studies.6,7 Regarding the present study, a careful examination of the data raises several issues. First, the number of channels per participant varied considerably between cases. Second, the length of the laser and procedural time appear to be considerably long. Finally, the investigators included people (number unreported) with unstable angina who, for understandable reasons, could not exercise on a treadmill, who were imputed with a baseline exercise time of zero. Such methodology inevitably contributes to the calculated gain in exercise duration of all participants during follow-up.The PMR group’s improvement in angina classification versus the medically treated was statistically significant. However, it is well known that investigators usually assign significantly lower baseline angina class scores to people undergoing PMR than a blinded objective panel.8 Importantly, the participants were not blinded to the treatment and the actual number of people reaching the 12 month goal was not reported.The lack of a straightforward statement regarding the actual number of people completing full follow-up or a concern regarding low number of participants reaching complete follow-up were sources of criticism aimed at earlier reports on EclipseTMR trial and Eclipse coronary studies.9 The procedural success and complications encountered in this study merit special examination. Using the authors’ definition of success (we note as well that stroke, severe hemodynamic deterioration and ventricular fibrillation were omitted from the definition) it appears that the success rate was 91%, not 96% as reported. Altogether, there were 20 procedural adverse events
among the 64 people in theTMR group, thus, reaching a 31% rate for procedural related complications. This, by all accounts, is an ominously high rate.The fact that this rate was encountered by a group of highly qualified operators is important. In less experienced hands it would have been higher. Specifically, focusing on the incidence of death, stroke, tamponade, myocardial hematoma and severe hypotension requiring IABP, an unacceptable high rate of 21% (14 of 64 participants) is revealed. This finding, in my opinion, is a testimony to the inadequate control and unsatisfactory yield of the applied laser system. Finally, it is revealing that the investigators conclusions include a statement on the effectiveness of the Eclipse holmium:YAG system for PMR, but carefully refrain from mentioning its safety. The readers of the study will inevitably need to fill in that void.Overall, this study confirms other, well-documented evidence that the results of recent myocardial revascularization trials are conflicting, suggesting a significant placebo effect in the response to PMR. 1 A serious concern regarding the rate and severity of PMR related complications must be expressed and further discussed. OnTopaz MD, FACC Professor of Medicine (Cardiology) & Pathology Director, Interventional Cardiology McGuire Veterans Affairs Medical Center Medical College of Virginia Virginia Commonwealth University Richmond,Virginia USA
Literature cited 1. Sariran M, Eisenberg MJ. Myocardial laser revascularization for the treatment of end-stage coronary artery disease. JACC 2003; 41: 173^183. 2. Topaz O. In: Topol EJ (ed.) Laser inTextbook of Interventional Cardiology, 4th edn. Philadelphia: WB Saunders, 2003: 675^703. 3. Topaz O. Plaque removal and thrombus dissolution with pulsed-wave lasers’ photoacoustic energy-biotissue interactions and their clinical manifestations. Cardiology 1996; 87: 384 ^391. 4. Burkhoof D, Fisher PE, Appelbaum M et al. Histologic appearance of transmyocardial laser channels after 4 1/2 weeks. Ann Thorac Surg 1996; 61: 1532^1534. 5. Chu VF, Giaid A, Kuang JQ et al. Angiogenesis in transmyocardial revascularization: comparison of laser versus mechanical punctures. AnnThorac Surg 1999; 68: 301^307. 6. Minisi AJ,Topaz O, Quinn MS, Mohanty LB.Cardiac nocieptive reflexes after transmyocardial laser revascularization: implications for the neural hypothesis of angina relief. J Thorac Cardiovasc Surg 2001; 122: 712^719. 7. Hirsch GM, Thompson GW, Arora RC, Hirsh KJ, Sullivan JA, Armdur JA. Transmyocardial laser revascularization does not denervate the canine heart. Ann Thorac Surg 1999; 68: 460 ^ 468. 8. Oesterle SN, SanbornTA, Ali N et al. Percutaneous transmyocardial laser revascularization for severe angina: the PACIFIC randomized trial: Potential Class Improvement From Intramyocardial Channels. Lancet 2000; 356: 1705^1710. 9. Topaz O, McIvor M, Stone GW et al. Acute results, complications and effect of lesion characteristics on outcome with the solid-state, pulsed-wave mid-infrared laser angioplasty system: final multicenter report. Laser Surg Med 1998; 22: 228 ^239.
Evidence-based Cardiovascular Medicine (2003) 7, 164 ^165
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Percutaneous myocardial revascularisation using the holmium-YAG laser is effective for refractory angina Abstracted from: Whitlow PL, DeMaio SJ, Perin EC et al. One-year results of percutaneous myocardial revascularisation for refractory angina pectoris. Am J Cardiol 2003; 91: 1342^1346.
BACKGROUND Studies have shown percutaneous myocardial revascularisation (PMR) to be e¡ective in the treatment of angina. A number of systems for PMR exist using either single or multiple laser pulses and varying optical ¢bre thickness. OBJECTIVE To compare PMR using a 1mm triple pulsed optical ¢bre holmium-YAG laser with maximal medical therapy for refractory angina pectoris. SETTING Twenty centres in the United States; study concludedJanuary 2000. METHOD Randomised controlled trial. PARTICIPANTS Three hundred and thirty people with refractory Canadian class III or IVangina ineligible for coronary bypass grafting and percutaneous intervention and on a maximal medical programme. Inclusion criteria included angina during exercise stress test or at rest (people unable to complete exercise stress test due to hospitalisation and intravenous nitroglycerin for recurrent rest pain were also included and given a test time of 0); left ventricular ejection fraction X30%; target area wall thickness X9 mm. Exclusion criteria included myocardial infarction in previous 3 weeks; medical comorbidity prohibiting treadmill exercise; signi¢cant aortic stenosis; mechanical aortic valve, and left ventricular thrombus. INTERVENTION Participants either continued to receive their medical treatment alone or medical treatment plus PMR. Participants were treated with
164
Evidence-based Cardiovascular Medicine (2003) 7,164 ^165 doi:10.1016/j.ebcm.2003.08.010
325 mg/day aspirin for 41 day before receiving PMR with a 1mm triple pulsed optical ¢bre holmium-YAG laser. The ischaemic area was covered with between 8 and 30 channels approximately 1 cm apart. Participants continued to take 325 mg/day aspirin inde¢nitely after the procedure. OUTCOMES The primary endpoint was at least a 60 second increase in exercise time (Naughton protocol stress test) at1year. Other main outcomes were improvement in function by X2 functional classes, and quality of life (Duke Activity Status score). MAIN RESULTS PMR was more e¡ective than medication alone for the primary outcome (58% PMR v 33% medication alone; p = 0.001). A signi¢cantly greater proportion of participants who received PMR improved X2 functional classes (55% PMR v 31% medication alone; po0.001). PMR improved quality of life compared with medication alone (improvement on Duke Activity Status score: 10.0 units with PMR v 5.7 units with medication alone; p = 0.005). AUTHORS’ CONCLUSIONS PMR treatment using the holmium-YAG system according to the trial protocol improves exercise capability and quality of life. Sources offunding: Eclipse Surgical Technologies Correspondenceto: PWhitlow, Departmentof Cardiology, F25,The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USAE-mail: [email protected] Abstract provided by Bazian Ltd, London
Commentary Myocardial laser revascularization is a technique for treating symptomatic people with coronary artery disease who cannot be revascularized by PCI or CABGs.Transmyocardial laser revascularization (TMR) is performed surgically with the laser beam applied through an epicardial-into-myocardial approach. Percutaneous myocardial laser revascularization (PMR) is performed with a cardiac catheterization approach utilizing retrograde aortic technique whereby the laser catheter is positioned in the ventricle aiming the beam towards an endocardial-into-myocardial penetration.1 PMR appears to be associated with less morbidity thanTMR. The present study by Whitlow et al describes one year results of a prospective, randomized multicenter trial utilizing a solidstate, pulsed-wave, mid-infrared holmium:YAG laser system for PMR. Noteworthy, the qualifications and the reputation of the study’s investigator are excellent. Nevertheless, serious concerns exist regarding the limitations of myocardial revascularization in general and the study’s methodology and results in particular. The holmium:YAG lasers transmit their beams by an optical fiber2,3 and rely on thermal energy to create myocardial channels with the intent of delivering oxygenated blood into ischemic regions of the myocardium, thereby increasing myocardial perfusion. To date, several mechanisms explaining the action of PMR and TMR have been proposed. These include the open channel hypothesis, the angiogenesis process and sympathetic denervation of the myocardium.There is ample experimental and pathologic documentation refuting either the existence or the attributed beneficial effect of each of the above-mentioned mechanisms. The transmural channels obliterate shortly after the procedure eventually being replaced by scarred tissue.4 Neorevascularization or angiogenesis turned out to be a nonspecific response to tissue injury, which can be obtained by simple needle punctures.5 The notion that denervation accounts for reduction in angina severity has been successfully challenged and could not be supported by animal studies.6,7 Regarding the present study, a careful examination of the data raises several issues. First, the number of channels per participant varied considerably between cases. Second, the length of the laser and procedural time appear to be considerably long. Finally, the investigators included people (number unreported) with unstable angina who, for understandable reasons, could not exercise on a treadmill, who were imputed with a baseline exercise time of zero. Such methodology inevitably contributes to the calculated gain in exercise duration of all participants during follow-up.The PMR group’s improvement in angina classification versus the medically treated was statistically significant. However, it is well known that investigators usually assign significantly lower baseline angina class scores to people undergoing PMR than a blinded objective panel.8 Importantly, the participants were not blinded to the treatment and the actual number of people reaching the 12 month goal was not reported.The lack of a straightforward statement regarding the actual number of people completing full follow-up or a concern regarding low number of participants reaching complete follow-up were sources of criticism aimed at earlier reports on EclipseTMR trial and Eclipse coronary studies.9 The procedural success and complications encountered in this study merit special examination. Using the authors’ definition of success (we note as well that stroke, severe hemodynamic deterioration and ventricular fibrillation were omitted from the definition) it appears that the success rate was 91%, not 96% as reported. Altogether, there were 20 procedural adverse events
among the 64 people in theTMR group, thus, reaching a 31% rate for procedural related complications. This, by all accounts, is an ominously high rate.The fact that this rate was encountered by a group of highly qualified operators is important. In less experienced hands it would have been higher. Specifically, focusing on the incidence of death, stroke, tamponade, myocardial hematoma and severe hypotension requiring IABP, an unacceptable high rate of 21% (14 of 64 participants) is revealed. This finding, in my opinion, is a testimony to the inadequate control and unsatisfactory yield of the applied laser system. Finally, it is revealing that the investigators conclusions include a statement on the effectiveness of the Eclipse holmium:YAG system for PMR, but carefully refrain from mentioning its safety. The readers of the study will inevitably need to fill in that void.Overall, this study confirms other, well-documented evidence that the results of recent myocardial revascularization trials are conflicting, suggesting a significant placebo effect in the response to PMR. 1 A serious concern regarding the rate and severity of PMR related complications must be expressed and further discussed. OnTopaz MD, FACC Professor of Medicine (Cardiology) & Pathology Director, Interventional Cardiology McGuire Veterans Affairs Medical Center Medical College of Virginia Virginia Commonwealth University Richmond,Virginia USA
Literature cited 1. Sariran M, Eisenberg MJ. Myocardial laser revascularization for the treatment of end-stage coronary artery disease. JACC 2003; 41: 173^183. 2. Topaz O. In: Topol EJ (ed.) Laser inTextbook of Interventional Cardiology, 4th edn. Philadelphia: WB Saunders, 2003: 675^703. 3. Topaz O. Plaque removal and thrombus dissolution with pulsed-wave lasers’ photoacoustic energy-biotissue interactions and their clinical manifestations. Cardiology 1996; 87: 384 ^391. 4. Burkhoof D, Fisher PE, Appelbaum M et al. Histologic appearance of transmyocardial laser channels after 4 1/2 weeks. Ann Thorac Surg 1996; 61: 1532^1534. 5. Chu VF, Giaid A, Kuang JQ et al. Angiogenesis in transmyocardial revascularization: comparison of laser versus mechanical punctures. AnnThorac Surg 1999; 68: 301^307. 6. Minisi AJ,Topaz O, Quinn MS, Mohanty LB.Cardiac nocieptive reflexes after transmyocardial laser revascularization: implications for the neural hypothesis of angina relief. J Thorac Cardiovasc Surg 2001; 122: 712^719. 7. Hirsch GM, Thompson GW, Arora RC, Hirsh KJ, Sullivan JA, Armdur JA. Transmyocardial laser revascularization does not denervate the canine heart. Ann Thorac Surg 1999; 68: 460 ^ 468. 8. Oesterle SN, SanbornTA, Ali N et al. Percutaneous transmyocardial laser revascularization for severe angina: the PACIFIC randomized trial: Potential Class Improvement From Intramyocardial Channels. Lancet 2000; 356: 1705^1710. 9. Topaz O, McIvor M, Stone GW et al. Acute results, complications and effect of lesion characteristics on outcome with the solid-state, pulsed-wave mid-infrared laser angioplasty system: final multicenter report. Laser Surg Med 1998; 22: 228 ^239.
Evidence-based Cardiovascular Medicine (2003) 7, 164 ^165
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