- Email: [email protected]
Advances in the treatment of coronary artery disease
Advances in the Treatment of Coronary Artery Disease Michael J. Mack, MD Cardiopulmonary Research Science and Technology Institute and Medical City Dallas Hospital, Dallas, Texas
Initial pioneering efforts of direct coronary artery bypass were all performed on a beating heart. Although originally introduced into cardiac surgery for the repair of intracardiac defects, the ability of John Gibbon’s heartlung machine to create a motionless, bloodless operative field catalyzed coronary artery bypass surgery. During the ensuing decades tens of millions of patients benefited from coronary revascularization on cardiopulmonary bypass. As we celebrate the 50th anniversary of the invention of the heart-lung machine the landscape of interventional treatment of coronary artery disease has shifted dramatically. Although instrumental in the genesis of the field of coronary revascularization, the role of
the heart-lung machine has now diminished. Two thirds of all coronary revascularization is now performed by percutaneous approaches and one fourth of all coronary artery bypass grafting procedures are performed without the heart-lung machine. However owing to the complexity of patients now requiring revascularization as well as recently introduced incremental improvements to cardiopulmonary bypass including coated, low prime circuits, closed integrated systems, and pharmacologic adjuncts Gibbon’s heart-lung machine will continue to play an integral role in this field. (Ann Thorac Surg 2003;76:S2240 –5) © 2003 by The Society of Thoracic Surgeons
A
The First 50 Years
SUPPLEMENT
t this 50th anniversary of the invention of the heartlung machine it is fitting to acknowledge the central role that the invention and its development has played in the management of coronary artery disease. There is probably no medical device that has had a greater impact on patient’s lives and influenced the management of a disease more than John Gibbon’s heart-lung machine. I am humbled by the opportunity to place in perspective the central role of Dr Gibbon and his magnificent machine at this symposium of the true giants of cardiac surgery. The ensuing 50 years since the successful introduction of the heart-lung machine in clinical practice have seen dramatic paradigm shifts in the management of coronary artery disease. From the risk factor modification by diet, lipid-lowering agents, smoking cessation, exercise, and medical therapy to the introduction in the 1970s of catheter-based intervention, to the rediscovery of “pumpless” coronary artery bypass grafting in the late 1990s, disease management of ischemic heart disease has shifted dramatically. Before addressing the central role of the heart-lung machine in surgery for coronary artery disease I will first address the antecedent events that set the stage for the introduction of cardiopulmonary bypass into the treatment of coronary artery disease.
Presented at the symposium, “Gibbon & His Heart-Lung Machine: 50 Years & Beyond,” Philadelphia, PA, May 2, 2003. Address reprint requests to Dr Mack, 7777 Forest Lane, Suite A323, Dallas, TX 75230; e-mail: [email protected].
© 2003 by The Society of Thoracic Surgeons Published by Elsevier Inc
Early Surgical Treatment of Coronary Artery Disease The surgical treatment of coronary artery disease began in the early part of the 20th century. It had been recognized in the mid-19th century that there was an association between coronary artery obstruction and the clinical syndrome of angina pectoris. The initial human surgical attempts to relieve angina were by a thoracocervical sympathectomy to denervate the heart in 1913. Subsequent surgical attempts included thyroidectomy to lower the metabolic demands placed upon the heart [1]. However it was actually about this time that the father of vascular surgery, Alexis Carrel, began investigation into the field of improving blood supply to the heart. He anastomosed an innominate artery of a dog to the coronary artery of a second dog on a beating heart in 1910 [2]. He also made the assessment at that time that it would be optimal to develop a heart-lung machine to stop the heart and protect the brain while performing the anastomosis. Attempts in humans to more directly address coronary artery disease would wait a number of decades however. In 1935 Claude Beck devised a procedure in which he abraded the pericardium and grafted pectoralis muscle or omentum as a method of stimulating additional myocardial blood supply [3]. Beck subsequently developed two other procedures, the Beck I operation in which he added a partial occlusion of the coronary sinus and the Beck II operation in which the brachial artery was interposed between the aorta and coronary sinus to retrograde perfuse the myocardium along with partial ligation of the coronary sinus [4, 5]. 0003-4975/03/$30.00 doi:10.1016/j.athoracsur.2003.09.005
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Subsequently other attempts to increase myocardial blood flow were stimulated by the work of Vineberg who in 1946 implanted the cut end of an internal mammary artery directly into the myocardium and performed this operation in hundreds of patients during the next 15 years [6]. Direct coronary artery bypass grafting was first demonstrated experimentally by Demikhov in 1952 using an internal mammary artery graft experimentally in dogs [7]. In 1957 Bailey reported coronary endarterectomy in humans and in the following year Longmire also reported successful coronary endarterectomy [8, 9]. The field of coronary revascularization was given a significant unexpected boost by the inadvertent discovery of direct coronary angiography by Mason Sones at the Cleveland Clinic in 1959 during performance of aortography [10, 11]. This technique of directly demonstrating the sites of coronary obstruction radiographically significantly catalyzed the whole field. The first internal mammary artery graft in humans was performed by Kolesov on a beating heart in Leningrad in 1964 [12]. With a recent resurgence of interest in beating heart surgery these initial historical chapters have recently been eloquently retold by Dr Kolesov’s son, Evengenii, in many beating heart surgery symposiums.
Introduction of the Heart-Lung Machine
Fig 1. John H. Gibbon, Jr, with his wife, Mary H. Gibbon, and his original heart-lung machine.
adoptable. The introduction of cardiopulmonary bypass facilitated the technical performance of coronary artery bypass surgery by creating a motionless, bloodless field that led to broad application of therapy to millions of
SUPPLEMENT
Inventions usually occur to address an unmet need. Frequently however the ultimate, most impactful application of an invention is not the one for which it was designed or intended but one that was never envisioned by its inventor. There are a plethora of examples of this throughout history from portable telecommunications to personal computers to spin-offs from the space program. Gibbons original intent in inventing the heart-lung machine was of course to be able to surgically repair intracardiac defects. Doctor Gibbon began developing an artificial device for bypassing the heart and lungs in 1931 [12]. By 1935 he had successfully used a prototype heartlung bypass machine to keep a cat alive for 26 minutes. After the interruption of World War II a series of new experiments in dogs in the 1950s commenced using IBM-built machines and culminated in the first successful use of the heart-lung machine in humans (Figs 1 and 2). On May 6, 1953, an 18-year-old woman became the first human to successfully undergo open heart surgery with a machine totally supporting her heart and lung function [13]. Although hundreds of thousands of patients have benefited from intracardiac applications of cardiopulmonary bypass for repair of congenital heart defects and valvular disease, the overall impact on the intended application is small compared with the tens of millions of patients who have undergone coronary revascularization made possible by the introduction of the heart-lung machine. Although the pioneers of coronary revascularization were able to successfully perform direct coronary revascularization on a beating heart, the technical challenges at the time of performing a precise vascular anastomosis made the addition of facilitating technology necessary to make the procedure widely applicable and
Fig 2. Reproduction of the original heart-lung machine at the 50th anniversary symposium.
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people over the subsequent 50 years. The heart-lung machine catalyzed the field of coronary artery bypass graft (CABG) surgery by enabling the operation to become so surgeon and patient friendly that it could be performed successfully worldwide in academic and community institutions alike by thousands of surgeons with generally excellent results. This disruptive technology allowed direct coronary artery revascularization not thought possible. In 1962 Sabiston performed the first successful saphenous vein graft from the ascending aorta to the distal right coronary artery [14]. Garrett, DeBakey, and Dennis also reported cases performed in 1964 [15]. By 1971 Favoloro and Effler at the Cleveland Clinic reported on 741 cases of coronary artery bypass grafting performed with saphenous vein grafts and cardiopulmonary bypass on an arrested heart [16]. The ultimate value of a disruptive technology such as cardiopulmonary bypass is due not necessarily to the original invention alone but to the subsequent incremental improvements. Indeed many incremental improvements in cardiopulmonary bypass surgery have been made in the last 40 years that have enhanced both early and late outcomes by decreasing procedural morbidity and enhancing user friendliness. Such incremental improvements include replacing roller pumps with centrifugal pumps, bubble oxygenators with membrane oxygenators, and new cannula designs and circuit coating. Perioperative morbidity and mortality have been further reduced by improvements in myocardial protection by the introduction of crystalloid cardioplegia and subsequently blood cardioplegia and retrograde myocardial preservation techniques [17]. The long-term results of the operation were significantly improved by the widespread use of arterial grafting [18 –20]. Despite the significant incremental improvements made, significant adverse events still occur owing to the use of cardiopulmonary bypass. The inflammatory response generated by the exposure to nonendothelial cell surfaces of blood during cardiopulmonary bypass incites a powerful inflammatory response that causes the release of a host of microembolic, vasoactive, cytotoxic substances that affect every organ and tissue within the body [21].
The Next 50 Years SUPPLEMENT
Percutaneous Coronary Intervention The enduring nature of coronary artery bypass grafting bespeaks of its long history, safety, and efficacy. It is a proven operation that can be reproducibly performed by a wide variety of surgeons with varying degrees of skill and acumen with generally good results. However there are significant complications of this procedure that may negate an otherwise successful result. History is replete with examples of the introduction of new technology that has significantly impacted the status quo. The examples of such disruptive technology include the replacement of silver film photography with digital techniques; the disruptive technology of cellular telecommunications has forever impacted the wire line telephone, digital printing
Ann Thorac Surg 2003;76:S2240 –5
has totally replaced offset printing, and closer to home the introduction of such disruptive technology as percutaneous coronary intervention by Greunitzig in 1979 and its subsequent iterative improvements has significantly affected the role of coronary artery bypass grafting in the management of coronary artery disease [22]. Although the number of coronary artery bypass graft procedures performed has doubled in the 24 years between 1979 and 2003 to approximately 800,000 procedures worldwide, the growth in percutaneous coronary intervention (PCI) has increased even more dramatically and eclipsed by a wide margin the number of interventions performed by a surgical approach. Reasons for this include the less invasive nature of the revascularization procedure with less procedural mortality and morbidity. It is estimated that there will be more than 1.5 million catheter-based procedures performed worldwide this year. In the United States the margin is even greater. In a recent review of experience in the HCA, Inc hospital system, 65.5% of all coronary revascularization was performed by PCI with only one third now being performed by coronary artery bypass grafting [23]. Furthermore although the total rate of coronary revascularization is increasing by 3.3% annually, this growth is totally due to the increase in percutaneous techniques, which have been increasing at a rate of 6.8% annually with a 2% annual decrement in the number of CABG procedures performed annually. With the introduction of drug-eluting stents occurring this year the Achilles heel of PCI, restenosis, is addressed. It has been further speculated that the role of surgical coronary revascularization will continue to decrease as a proportionate share of total revascularization procedures.
Minimally Invasive Coronary Artery Bypass Surgery Beginning in the mid-1990s two new surgical revascularization strategies were introduced in attempts at reducing the invasiveness of the standard coronary artery bypass grafting (CABG) procedure performed on cardiopulmonary bypass with ischemic arrest. Revascularization either on an arrested heart with peripheral cannulation through a small access incision (port access) or on a beating heart with a limited access approach (MIDCABG) was introduced [24, 25]. The lack of demonstrated benefit and the significant technical challenge associated with the port access approach have until now limited the application of that approach for coronary revascularization [26]. In a similar manner the technical challenges associated with the MIDCABG procedure as well as the ability to perform only a single vessel bypass and the rarity of single vessel disease at the present day has served to limit this approach [27]. However the recognition of improved outcomes in selected patients by the elimination of cardiopulmonary bypass served as an impetus to develop off-pump coronary artery bypass (OPCAB) as a treatment option for patients with multivessel disease. Although the initial coronary artery bypass procedures were performed on a beating heart in the 1960s before utilization of Gibbon’s heart-lung machine, the creation of a motionless, bloodless field made further attempts at developing these techniques moot.
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Trial Van Dijk [32] Angelini [31] Puskas [33] Total
Fig 3. Suction exposure and suction stabilization for off-pump coronary artery bypass graft surgery.
Despite significant improvements made and the introduction of suction stabilization techniques to maintain a local rather than global, relatively motionless, bloodless field the awareness of the side effects associated with the systemic inflammatory response from cardiopulmonary bypass has led to renewed interest in the beating heart technique [28]. Since its introduction by Benetti and Subramanian in 1996 off-pump surgery has continued to grow so that currently it comprises approximately 25% of all CABG procedures performed in the United States [23]. Growth has been catalyzed by the introduction of suction stabilizer and suction exposure devices as well as technique advancements (Fig 3). There have now been more than a thousand peer review publications in the past 7 years that generally show equivalency or superiority of off-pump surgery compared with the gold standard arrested heart (on-pump) surgery. These have now been summarized in two recent reviews [29, 30]. However there are only three prospective, randomized studies comparing the two techniques [31–33]. A meta-analysis Table 1. Coronary Artery Bypass Graft Surgery: On- Versus Off-Pump Randomized Trials, Operative Mortality Author Van Dijk [32] Angelini [31] Puskas [33] Total
Number On-Pump
Number of Deaths
Number Off-Pump
Number of Deaths
139 201 99 439
0 2 2 4 (0.9%)
142 200 98 440
0 0 1 1 (0.2%)
Number On-Pump
Number of Strokes
Number Off-Pump
Number of Strokes
139 201 99 439
2 0 2 4 (0.9%)
142 200 98 440
1 0 1 2 (0.4%)
of these three trials, which comprised a total of 879 patients, reveals an off-pump mortality rate of 0.2% compared with an on-pump mortality rate of 0.9% (Table 1). Even the meta-analyses are underpowered to show a significant difference however. In addition the incidence of stroke is less off pump compared with on pump, although again the results do not reach statistical significance (Table 2). The percent of patients requiring transfusion is approximately 50% off-pump compared with on-pump surgery (Table 3). Comparison of large databases yields further information regarding potential benefits of off-pump surgery. The annual mortality for the Society of Thoracic Surgeons (STS) national database from 1999 through 2002 has shown a significant decrease in mortality correlating with the introduction of off-pump techniques (Fig 4) [34]. The HCA national database similarly has shown an overall decrement in the operative mortality rate associated with the introduction of off-pump surgery (Fig 5) [23]. Have we now come full circlein the last half century? Is this really a manifestation of a “less is more” paradigm? Can Gibbon’s sophisticated heart-lung machine, even with the associated technological enhancements to the original invention, really be replaced by simpler tools? Although off-pump surgery now comprises one fourth of all coronary revascularization, its further growth is not a given. The technologic and technique hurdles challenging surgeons continue to limit adoption. The lack of clinical validation by large randomized trials as well as the limitations of surgical education have also limited adoption. Despite the challenges posed by less invasive coronary revascularization techniques however, including drugeluting stents, the significant incremental improvements to CABG continue to occur. Endoscopic positioners and stabilizers to facilitate limited access CABG hold the Table 3. Coronary Artery Bypass Graft Surgery: On- Versus Off-Pump Randomized Trials, Transfusions Trial Van Dijk (32) Angelini (31) Puskas (33) Total
Number Percent Number Percent On-Pump Transfused Off-Pump Transfused 139 201 99 439
29 49 44 41.4%
142 200 98 440 P ⬍ 0.01
28 18 26 20.6%
SUPPLEMENT
Table 2. Coronary Artery Bypass Graft Surgery: On- Versus Off-Pump Randomized Trials, Stroke
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Fig 4. Isolated coronary artery bypass graft surgery (CABG) operative mortality in The Society of Thoracic Surgeons national database 1990 to 2002. (Solid bars ⫽ CABG mortality; diagonal-line bars ⫽ on pump; vertical-line bars ⫽ off pump.)
promise of truly allowing limited access beating heart multivessel coronary revascularization. The role of robotics and anastomotic devices to facilitate or eliminate sutured limited access anastomosis are also promising (Fig 6). Despite the proven benefit of long-term results with arterial grafting, saphenous vein grafts still remain the predominant conduit employed. Recently introduced have been intraoperative saphenous vein graft treatment with blockers (E2F decoy) to limit upregulation of gene expression in the vessel endothelium to prevent neointimal hyperplasia and graft arteriosclerosis and to prolong graft patency. The current Prevent IV trial is a 3,000patient multicenter randomized trial at more than 100 STS national database sites in the United States. If results of this trial are positive as the early small pilot studies have been the long-term results of coronary artery bypass grafting could be significantly improved. Progress in coronary artery bypass surgery has not been limited to off-pump surgery. Advanced circulatory
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Fig 6. Magnetic anastomotic device.
SUPPLEMENT
support systems that integrate pump, oxygenator, and air removal systems into a single unit to minimize systemic and inflammatory response and hemodilution has been introduced to improve the results with on-pump coronary artery bypass surgery [35]. By limiting the priming volume and exposed foreign surface area, by improving gas exchange, and by minimizing foreign surface area contact on-pump conventional CABG surgery may be improving. In conclusion cardiac surgery is currently in the midst of a major paradigm shift. Coronary artery bypass grafting using current iterations of Gibbon’s heart-lung machine will continue to remain a major technique for coronary artery bypass operations in the foreseeable future. However with the success of competitive revascularization techniques including off-pump CABG surgery and percutaneous techniques, the predominant role of the Gibbon heart-lung machine in coronary revascularization will continue to decrease. The road to limited access multivessel CABG surgery will continue to be a difficult one; however progress is being made. The complexity of patients undergoing surgical revascularization will continue to increase and the diversification of the procedures within cardiac surgery will continue to grow. The contribution of Gibbon’s heart-lung machine will only increase in historical stature even though the future role for on-pump CABG will diminish.
References
Fig 5. Coronary artery bypass graft surgery (CABG) operative mortality HCA, Inc casemix database 1999 to 2002. (Solid bars ⫽ all CABG; diagonal-line bars ⫽ on pump; gray shaded bars ⫽ off pump; line ⫽ linear [all CABG].)
1. Bojar RM. Coronary artery bypass surgery. In: Adult cardiac surgery. Massachusetts: Blackwell Scientific, 1992:79. 2. Carrel A. On the experimental surgery of the thoracic aorta and heart. Am J Surg 1919;52:83. 3. Beck CS. The development of a new blood supply to the heart by operation: Ann Surg 1935;102:801. 4. Beck CS. The development of a new blood supply to the heart by operation. In: Levy RL, ed. Disease of the coronary arteries and cardiac pain. Chapter 17. New York: Macmillan, 1936. 5. Beck CS. Coronary sclerosis and angina pectoris: treatment by grafting a new blood supply upon the myocardium. Surg Gynecol Obstet 1937;64:270.
6. Vineberg AM. Development of an anastomosis between the coronary vessels and a transplanted internal mammary artery. Can Med Assoc J 1946;55:117. 7. Demikhov VP. Experimental transplantation of vital organs [Authorized translation from the Russian by Basil Haigh.]. New York: Consultants Bureau, 1962. 8. Bailey CP, May A, Lemmon WM. Survival after coronary endarterectomy in man. JAMA 1957;164:641. 9. Longmire WP Jr, Cannon JA, Kattus AA. Direct vision coronary endarterectomy for angina pectoris. N Engl J Med 1958;259:993. 10. Sones FM. Acquired heart disease: symposium on present and future cineangiocardiography. Am J Cardiol 1959;3:710. 11. Sones FM, Shirley EK. Cine coronary arteriography. Mod Concepts Cardiovasc Dis 1962;31:735. 12. Kolessov VI. Mammary artery– coronary artery anastomosis as a method of treatment for angina pectoris. J Thorac Cardiovasc Surg 1967;54:535. 13. Gibbon JH Jr. Application of a mechanical heart and lung apparatus to cardiac surgery. Minn Med 1954;37:171. 14. Sabiston DC Jr. The coronary circulation. Johns Hopkins Med J 1974;134:314. 15. Garrett HE, Dennis EW, DeBakey ME. Aortocoronary bypass with saphenous vein grafts: seven-year follow-up. JAMA 1973;223:729. 16. Favaloro RG, Effler DB, Groves LK. Severe segmental obstruction of the left main coronary artery and its divisions: surgical treatment by the saphenous vein graft technic. J Thorac Cardiovasc Surg 1970;60:469. 17. Gay WA Jr, Ebert PA. Functional metabolic and morphologic effects of potassium-induced cardioplegia. Surgery 1973;74: 284. 18. Green GE, Stertzer SH, Gordon RB, et al. Anastomosis of the internal mammary artery to the distal left anterior descending coronary artery. Circulation 1970;41:79. 19. Loop FD, Lytle BW, Cosgrove DM, et al. Influence of the internal mammary artery on 10-year survival and other cardiac events. N Engl J Med 1986;314:1. 20. Lytle BW, Blackstone EH, Loop FD, et al. Two internal thoracic artery grafts are better than one. J Thorac Cardiovasc Surg 1999;117:855–72. 21. Edmunds LH Jr, Hessell EA, Colman RW, Menasche P, Hammon JW Jr. Extracorporeal circulation. Introduction. In: Cohn LH, Edmunds LH Jr, eds. Cardiac surgery in the adult. 2nd ed. New York: McGraw-Hill, 2003:316. 22. Gruentiz A. Transluminal dilation of coronary artery stenosis. Lancet 1978;1:263. 23. Mack MJ, Brown PP, Kugelmass AD, et al. Current status and outcomes of coronary revascularization 1999-2002. Sur-
GIBBON’S HEART-LUNG MACHINE MACK ADVANCES IN TREATING CAD
24.
25.
26.
27.
28. 29. 30. 31.
32.
33.
34.
35.
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gical and percutaneous procedures. Ann Thorac Surg 2003 (In press). Benetti F, Mariani MA, Sani G, et al. Video-assisted minimally invasive coronary operations without cardiopulmonary bypass: a multi-center study. J Thorac Cardiovasc Surg 1996;112:1478 –84. Reichenspurner H, Gulielmos V, Wunderlich J, et al. Portaccess coronary artery bypass grafting with the use of cardiopulmonary bypass, and cardioplegic arrest. Ann Thorac Surg 1998;65:413–9. Dewey TM, Mack MJ. Myocardial revascularization without cardiopulmonary bypass. In: Cohn LH, Edmunds LH Jr, eds. Cardiac surgery in the adult. 2nd ed. New York: McGrawHill, 2003:609. Diegler A, Spyrantis N, Matin M, et al. The revival of surgical treatment for isolated proximal high-grade LAD lesions by minimally invasive coronary artery bypass grafting. Eur J Cardiothorac Surg 2000;17:501. Jansen EW, Lahpor JR, Borst C, Grundeman PF, Bredee JJ. Off-pump coronary bypass grafting: how to use the Octopus tissue stabilizer. Ann Thorac Surg 1998;66:576 –9. Connolly MW. Current results of off-pump coronary artery bypass surgery. Semin Thorac Cardiovasc Surg 2003;15:45– 51. Mack MJ. Beating heart surgery: does it make a difference? Am Heart Hosp J 2003;1:149 –57. Angelini GD, Taylor FC, Reeves BC, et al. Early and midterm outcomes after off-pump and on-pump surgery in Beating Heart Against Cardioplegic Arrest Studies (BHACAS 1 and 2): a pooled analysis of two randomized controlled trials. Lancet 2002;359:1194 –9. van Dijk D, Nierich AP, Jansen EWL, et al. Early outcome after off-pump versus on-pump coronary bypass surgery: results from a randomized study. Circulation 2001;104: 1761–6. Puskas JD, William WH, Duke PG, et al. Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay. A prospective randomized comparison of two hundred unselected patients undergoing off-pump versus conventional coronary artery bypass grafting. J Thorac Cardiovasc Surg 2003;125:797–808. Society of Thoracic Surgeons. STS national database executive summary. Available at: http://ctsnet.org/file/ stsnationaldatabasefall2002executive summary.pdf. Accessed 22 January 2003. Mueller XM, Jegger D, Augstburger M, Horisberger J, Godar G, von Segesser LK. A new concept of integrated cardiopulmonary bypass circuit. Eur J Cardiothorac Surg 2002;21: 840 –6.
SUPPLEMENT
Ann Thorac Surg 2003;76:S2240 –5
Initial pioneering efforts of direct coronary artery bypass were all performed on a beating heart. Although originally introduced into cardiac surgery for the repair of intracardiac defects, the ability of John Gibbon’s heartlung machine to create a motionless, bloodless operative field catalyzed coronary artery bypass surgery. During the ensuing decades tens of millions of patients benefited from coronary revascularization on cardiopulmonary bypass. As we celebrate the 50th anniversary of the invention of the heart-lung machine the landscape of interventional treatment of coronary artery disease has shifted dramatically. Although instrumental in the genesis of the field of coronary revascularization, the role of
the heart-lung machine has now diminished. Two thirds of all coronary revascularization is now performed by percutaneous approaches and one fourth of all coronary artery bypass grafting procedures are performed without the heart-lung machine. However owing to the complexity of patients now requiring revascularization as well as recently introduced incremental improvements to cardiopulmonary bypass including coated, low prime circuits, closed integrated systems, and pharmacologic adjuncts Gibbon’s heart-lung machine will continue to play an integral role in this field. (Ann Thorac Surg 2003;76:S2240 –5) © 2003 by The Society of Thoracic Surgeons
A
The First 50 Years
SUPPLEMENT
t this 50th anniversary of the invention of the heartlung machine it is fitting to acknowledge the central role that the invention and its development has played in the management of coronary artery disease. There is probably no medical device that has had a greater impact on patient’s lives and influenced the management of a disease more than John Gibbon’s heart-lung machine. I am humbled by the opportunity to place in perspective the central role of Dr Gibbon and his magnificent machine at this symposium of the true giants of cardiac surgery. The ensuing 50 years since the successful introduction of the heart-lung machine in clinical practice have seen dramatic paradigm shifts in the management of coronary artery disease. From the risk factor modification by diet, lipid-lowering agents, smoking cessation, exercise, and medical therapy to the introduction in the 1970s of catheter-based intervention, to the rediscovery of “pumpless” coronary artery bypass grafting in the late 1990s, disease management of ischemic heart disease has shifted dramatically. Before addressing the central role of the heart-lung machine in surgery for coronary artery disease I will first address the antecedent events that set the stage for the introduction of cardiopulmonary bypass into the treatment of coronary artery disease.
Presented at the symposium, “Gibbon & His Heart-Lung Machine: 50 Years & Beyond,” Philadelphia, PA, May 2, 2003. Address reprint requests to Dr Mack, 7777 Forest Lane, Suite A323, Dallas, TX 75230; e-mail: [email protected].
© 2003 by The Society of Thoracic Surgeons Published by Elsevier Inc
Early Surgical Treatment of Coronary Artery Disease The surgical treatment of coronary artery disease began in the early part of the 20th century. It had been recognized in the mid-19th century that there was an association between coronary artery obstruction and the clinical syndrome of angina pectoris. The initial human surgical attempts to relieve angina were by a thoracocervical sympathectomy to denervate the heart in 1913. Subsequent surgical attempts included thyroidectomy to lower the metabolic demands placed upon the heart [1]. However it was actually about this time that the father of vascular surgery, Alexis Carrel, began investigation into the field of improving blood supply to the heart. He anastomosed an innominate artery of a dog to the coronary artery of a second dog on a beating heart in 1910 [2]. He also made the assessment at that time that it would be optimal to develop a heart-lung machine to stop the heart and protect the brain while performing the anastomosis. Attempts in humans to more directly address coronary artery disease would wait a number of decades however. In 1935 Claude Beck devised a procedure in which he abraded the pericardium and grafted pectoralis muscle or omentum as a method of stimulating additional myocardial blood supply [3]. Beck subsequently developed two other procedures, the Beck I operation in which he added a partial occlusion of the coronary sinus and the Beck II operation in which the brachial artery was interposed between the aorta and coronary sinus to retrograde perfuse the myocardium along with partial ligation of the coronary sinus [4, 5]. 0003-4975/03/$30.00 doi:10.1016/j.athoracsur.2003.09.005
Ann Thorac Surg 2003;76:S2240 –5
GIBBON’S HEART-LUNG MACHINE MACK ADVANCES IN TREATING CAD
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Subsequently other attempts to increase myocardial blood flow were stimulated by the work of Vineberg who in 1946 implanted the cut end of an internal mammary artery directly into the myocardium and performed this operation in hundreds of patients during the next 15 years [6]. Direct coronary artery bypass grafting was first demonstrated experimentally by Demikhov in 1952 using an internal mammary artery graft experimentally in dogs [7]. In 1957 Bailey reported coronary endarterectomy in humans and in the following year Longmire also reported successful coronary endarterectomy [8, 9]. The field of coronary revascularization was given a significant unexpected boost by the inadvertent discovery of direct coronary angiography by Mason Sones at the Cleveland Clinic in 1959 during performance of aortography [10, 11]. This technique of directly demonstrating the sites of coronary obstruction radiographically significantly catalyzed the whole field. The first internal mammary artery graft in humans was performed by Kolesov on a beating heart in Leningrad in 1964 [12]. With a recent resurgence of interest in beating heart surgery these initial historical chapters have recently been eloquently retold by Dr Kolesov’s son, Evengenii, in many beating heart surgery symposiums.
Introduction of the Heart-Lung Machine
Fig 1. John H. Gibbon, Jr, with his wife, Mary H. Gibbon, and his original heart-lung machine.
adoptable. The introduction of cardiopulmonary bypass facilitated the technical performance of coronary artery bypass surgery by creating a motionless, bloodless field that led to broad application of therapy to millions of
SUPPLEMENT
Inventions usually occur to address an unmet need. Frequently however the ultimate, most impactful application of an invention is not the one for which it was designed or intended but one that was never envisioned by its inventor. There are a plethora of examples of this throughout history from portable telecommunications to personal computers to spin-offs from the space program. Gibbons original intent in inventing the heart-lung machine was of course to be able to surgically repair intracardiac defects. Doctor Gibbon began developing an artificial device for bypassing the heart and lungs in 1931 [12]. By 1935 he had successfully used a prototype heartlung bypass machine to keep a cat alive for 26 minutes. After the interruption of World War II a series of new experiments in dogs in the 1950s commenced using IBM-built machines and culminated in the first successful use of the heart-lung machine in humans (Figs 1 and 2). On May 6, 1953, an 18-year-old woman became the first human to successfully undergo open heart surgery with a machine totally supporting her heart and lung function [13]. Although hundreds of thousands of patients have benefited from intracardiac applications of cardiopulmonary bypass for repair of congenital heart defects and valvular disease, the overall impact on the intended application is small compared with the tens of millions of patients who have undergone coronary revascularization made possible by the introduction of the heart-lung machine. Although the pioneers of coronary revascularization were able to successfully perform direct coronary revascularization on a beating heart, the technical challenges at the time of performing a precise vascular anastomosis made the addition of facilitating technology necessary to make the procedure widely applicable and
Fig 2. Reproduction of the original heart-lung machine at the 50th anniversary symposium.
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people over the subsequent 50 years. The heart-lung machine catalyzed the field of coronary artery bypass graft (CABG) surgery by enabling the operation to become so surgeon and patient friendly that it could be performed successfully worldwide in academic and community institutions alike by thousands of surgeons with generally excellent results. This disruptive technology allowed direct coronary artery revascularization not thought possible. In 1962 Sabiston performed the first successful saphenous vein graft from the ascending aorta to the distal right coronary artery [14]. Garrett, DeBakey, and Dennis also reported cases performed in 1964 [15]. By 1971 Favoloro and Effler at the Cleveland Clinic reported on 741 cases of coronary artery bypass grafting performed with saphenous vein grafts and cardiopulmonary bypass on an arrested heart [16]. The ultimate value of a disruptive technology such as cardiopulmonary bypass is due not necessarily to the original invention alone but to the subsequent incremental improvements. Indeed many incremental improvements in cardiopulmonary bypass surgery have been made in the last 40 years that have enhanced both early and late outcomes by decreasing procedural morbidity and enhancing user friendliness. Such incremental improvements include replacing roller pumps with centrifugal pumps, bubble oxygenators with membrane oxygenators, and new cannula designs and circuit coating. Perioperative morbidity and mortality have been further reduced by improvements in myocardial protection by the introduction of crystalloid cardioplegia and subsequently blood cardioplegia and retrograde myocardial preservation techniques [17]. The long-term results of the operation were significantly improved by the widespread use of arterial grafting [18 –20]. Despite the significant incremental improvements made, significant adverse events still occur owing to the use of cardiopulmonary bypass. The inflammatory response generated by the exposure to nonendothelial cell surfaces of blood during cardiopulmonary bypass incites a powerful inflammatory response that causes the release of a host of microembolic, vasoactive, cytotoxic substances that affect every organ and tissue within the body [21].
The Next 50 Years SUPPLEMENT
Percutaneous Coronary Intervention The enduring nature of coronary artery bypass grafting bespeaks of its long history, safety, and efficacy. It is a proven operation that can be reproducibly performed by a wide variety of surgeons with varying degrees of skill and acumen with generally good results. However there are significant complications of this procedure that may negate an otherwise successful result. History is replete with examples of the introduction of new technology that has significantly impacted the status quo. The examples of such disruptive technology include the replacement of silver film photography with digital techniques; the disruptive technology of cellular telecommunications has forever impacted the wire line telephone, digital printing
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has totally replaced offset printing, and closer to home the introduction of such disruptive technology as percutaneous coronary intervention by Greunitzig in 1979 and its subsequent iterative improvements has significantly affected the role of coronary artery bypass grafting in the management of coronary artery disease [22]. Although the number of coronary artery bypass graft procedures performed has doubled in the 24 years between 1979 and 2003 to approximately 800,000 procedures worldwide, the growth in percutaneous coronary intervention (PCI) has increased even more dramatically and eclipsed by a wide margin the number of interventions performed by a surgical approach. Reasons for this include the less invasive nature of the revascularization procedure with less procedural mortality and morbidity. It is estimated that there will be more than 1.5 million catheter-based procedures performed worldwide this year. In the United States the margin is even greater. In a recent review of experience in the HCA, Inc hospital system, 65.5% of all coronary revascularization was performed by PCI with only one third now being performed by coronary artery bypass grafting [23]. Furthermore although the total rate of coronary revascularization is increasing by 3.3% annually, this growth is totally due to the increase in percutaneous techniques, which have been increasing at a rate of 6.8% annually with a 2% annual decrement in the number of CABG procedures performed annually. With the introduction of drug-eluting stents occurring this year the Achilles heel of PCI, restenosis, is addressed. It has been further speculated that the role of surgical coronary revascularization will continue to decrease as a proportionate share of total revascularization procedures.
Minimally Invasive Coronary Artery Bypass Surgery Beginning in the mid-1990s two new surgical revascularization strategies were introduced in attempts at reducing the invasiveness of the standard coronary artery bypass grafting (CABG) procedure performed on cardiopulmonary bypass with ischemic arrest. Revascularization either on an arrested heart with peripheral cannulation through a small access incision (port access) or on a beating heart with a limited access approach (MIDCABG) was introduced [24, 25]. The lack of demonstrated benefit and the significant technical challenge associated with the port access approach have until now limited the application of that approach for coronary revascularization [26]. In a similar manner the technical challenges associated with the MIDCABG procedure as well as the ability to perform only a single vessel bypass and the rarity of single vessel disease at the present day has served to limit this approach [27]. However the recognition of improved outcomes in selected patients by the elimination of cardiopulmonary bypass served as an impetus to develop off-pump coronary artery bypass (OPCAB) as a treatment option for patients with multivessel disease. Although the initial coronary artery bypass procedures were performed on a beating heart in the 1960s before utilization of Gibbon’s heart-lung machine, the creation of a motionless, bloodless field made further attempts at developing these techniques moot.
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Trial Van Dijk [32] Angelini [31] Puskas [33] Total
Fig 3. Suction exposure and suction stabilization for off-pump coronary artery bypass graft surgery.
Despite significant improvements made and the introduction of suction stabilization techniques to maintain a local rather than global, relatively motionless, bloodless field the awareness of the side effects associated with the systemic inflammatory response from cardiopulmonary bypass has led to renewed interest in the beating heart technique [28]. Since its introduction by Benetti and Subramanian in 1996 off-pump surgery has continued to grow so that currently it comprises approximately 25% of all CABG procedures performed in the United States [23]. Growth has been catalyzed by the introduction of suction stabilizer and suction exposure devices as well as technique advancements (Fig 3). There have now been more than a thousand peer review publications in the past 7 years that generally show equivalency or superiority of off-pump surgery compared with the gold standard arrested heart (on-pump) surgery. These have now been summarized in two recent reviews [29, 30]. However there are only three prospective, randomized studies comparing the two techniques [31–33]. A meta-analysis Table 1. Coronary Artery Bypass Graft Surgery: On- Versus Off-Pump Randomized Trials, Operative Mortality Author Van Dijk [32] Angelini [31] Puskas [33] Total
Number On-Pump
Number of Deaths
Number Off-Pump
Number of Deaths
139 201 99 439
0 2 2 4 (0.9%)
142 200 98 440
0 0 1 1 (0.2%)
Number On-Pump
Number of Strokes
Number Off-Pump
Number of Strokes
139 201 99 439
2 0 2 4 (0.9%)
142 200 98 440
1 0 1 2 (0.4%)
of these three trials, which comprised a total of 879 patients, reveals an off-pump mortality rate of 0.2% compared with an on-pump mortality rate of 0.9% (Table 1). Even the meta-analyses are underpowered to show a significant difference however. In addition the incidence of stroke is less off pump compared with on pump, although again the results do not reach statistical significance (Table 2). The percent of patients requiring transfusion is approximately 50% off-pump compared with on-pump surgery (Table 3). Comparison of large databases yields further information regarding potential benefits of off-pump surgery. The annual mortality for the Society of Thoracic Surgeons (STS) national database from 1999 through 2002 has shown a significant decrease in mortality correlating with the introduction of off-pump techniques (Fig 4) [34]. The HCA national database similarly has shown an overall decrement in the operative mortality rate associated with the introduction of off-pump surgery (Fig 5) [23]. Have we now come full circlein the last half century? Is this really a manifestation of a “less is more” paradigm? Can Gibbon’s sophisticated heart-lung machine, even with the associated technological enhancements to the original invention, really be replaced by simpler tools? Although off-pump surgery now comprises one fourth of all coronary revascularization, its further growth is not a given. The technologic and technique hurdles challenging surgeons continue to limit adoption. The lack of clinical validation by large randomized trials as well as the limitations of surgical education have also limited adoption. Despite the challenges posed by less invasive coronary revascularization techniques however, including drugeluting stents, the significant incremental improvements to CABG continue to occur. Endoscopic positioners and stabilizers to facilitate limited access CABG hold the Table 3. Coronary Artery Bypass Graft Surgery: On- Versus Off-Pump Randomized Trials, Transfusions Trial Van Dijk (32) Angelini (31) Puskas (33) Total
Number Percent Number Percent On-Pump Transfused Off-Pump Transfused 139 201 99 439
29 49 44 41.4%
142 200 98 440 P ⬍ 0.01
28 18 26 20.6%
SUPPLEMENT
Table 2. Coronary Artery Bypass Graft Surgery: On- Versus Off-Pump Randomized Trials, Stroke
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Fig 4. Isolated coronary artery bypass graft surgery (CABG) operative mortality in The Society of Thoracic Surgeons national database 1990 to 2002. (Solid bars ⫽ CABG mortality; diagonal-line bars ⫽ on pump; vertical-line bars ⫽ off pump.)
promise of truly allowing limited access beating heart multivessel coronary revascularization. The role of robotics and anastomotic devices to facilitate or eliminate sutured limited access anastomosis are also promising (Fig 6). Despite the proven benefit of long-term results with arterial grafting, saphenous vein grafts still remain the predominant conduit employed. Recently introduced have been intraoperative saphenous vein graft treatment with blockers (E2F decoy) to limit upregulation of gene expression in the vessel endothelium to prevent neointimal hyperplasia and graft arteriosclerosis and to prolong graft patency. The current Prevent IV trial is a 3,000patient multicenter randomized trial at more than 100 STS national database sites in the United States. If results of this trial are positive as the early small pilot studies have been the long-term results of coronary artery bypass grafting could be significantly improved. Progress in coronary artery bypass surgery has not been limited to off-pump surgery. Advanced circulatory
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Fig 6. Magnetic anastomotic device.
SUPPLEMENT
support systems that integrate pump, oxygenator, and air removal systems into a single unit to minimize systemic and inflammatory response and hemodilution has been introduced to improve the results with on-pump coronary artery bypass surgery [35]. By limiting the priming volume and exposed foreign surface area, by improving gas exchange, and by minimizing foreign surface area contact on-pump conventional CABG surgery may be improving. In conclusion cardiac surgery is currently in the midst of a major paradigm shift. Coronary artery bypass grafting using current iterations of Gibbon’s heart-lung machine will continue to remain a major technique for coronary artery bypass operations in the foreseeable future. However with the success of competitive revascularization techniques including off-pump CABG surgery and percutaneous techniques, the predominant role of the Gibbon heart-lung machine in coronary revascularization will continue to decrease. The road to limited access multivessel CABG surgery will continue to be a difficult one; however progress is being made. The complexity of patients undergoing surgical revascularization will continue to increase and the diversification of the procedures within cardiac surgery will continue to grow. The contribution of Gibbon’s heart-lung machine will only increase in historical stature even though the future role for on-pump CABG will diminish.
References
Fig 5. Coronary artery bypass graft surgery (CABG) operative mortality HCA, Inc casemix database 1999 to 2002. (Solid bars ⫽ all CABG; diagonal-line bars ⫽ on pump; gray shaded bars ⫽ off pump; line ⫽ linear [all CABG].)
1. Bojar RM. Coronary artery bypass surgery. In: Adult cardiac surgery. Massachusetts: Blackwell Scientific, 1992:79. 2. Carrel A. On the experimental surgery of the thoracic aorta and heart. Am J Surg 1919;52:83. 3. Beck CS. The development of a new blood supply to the heart by operation: Ann Surg 1935;102:801. 4. Beck CS. The development of a new blood supply to the heart by operation. In: Levy RL, ed. Disease of the coronary arteries and cardiac pain. Chapter 17. New York: Macmillan, 1936. 5. Beck CS. Coronary sclerosis and angina pectoris: treatment by grafting a new blood supply upon the myocardium. Surg Gynecol Obstet 1937;64:270.
6. Vineberg AM. Development of an anastomosis between the coronary vessels and a transplanted internal mammary artery. Can Med Assoc J 1946;55:117. 7. Demikhov VP. Experimental transplantation of vital organs [Authorized translation from the Russian by Basil Haigh.]. New York: Consultants Bureau, 1962. 8. Bailey CP, May A, Lemmon WM. Survival after coronary endarterectomy in man. JAMA 1957;164:641. 9. Longmire WP Jr, Cannon JA, Kattus AA. Direct vision coronary endarterectomy for angina pectoris. N Engl J Med 1958;259:993. 10. Sones FM. Acquired heart disease: symposium on present and future cineangiocardiography. Am J Cardiol 1959;3:710. 11. Sones FM, Shirley EK. Cine coronary arteriography. Mod Concepts Cardiovasc Dis 1962;31:735. 12. Kolessov VI. Mammary artery– coronary artery anastomosis as a method of treatment for angina pectoris. J Thorac Cardiovasc Surg 1967;54:535. 13. Gibbon JH Jr. Application of a mechanical heart and lung apparatus to cardiac surgery. Minn Med 1954;37:171. 14. Sabiston DC Jr. The coronary circulation. Johns Hopkins Med J 1974;134:314. 15. Garrett HE, Dennis EW, DeBakey ME. Aortocoronary bypass with saphenous vein grafts: seven-year follow-up. JAMA 1973;223:729. 16. Favaloro RG, Effler DB, Groves LK. Severe segmental obstruction of the left main coronary artery and its divisions: surgical treatment by the saphenous vein graft technic. J Thorac Cardiovasc Surg 1970;60:469. 17. Gay WA Jr, Ebert PA. Functional metabolic and morphologic effects of potassium-induced cardioplegia. Surgery 1973;74: 284. 18. Green GE, Stertzer SH, Gordon RB, et al. Anastomosis of the internal mammary artery to the distal left anterior descending coronary artery. Circulation 1970;41:79. 19. Loop FD, Lytle BW, Cosgrove DM, et al. Influence of the internal mammary artery on 10-year survival and other cardiac events. N Engl J Med 1986;314:1. 20. Lytle BW, Blackstone EH, Loop FD, et al. Two internal thoracic artery grafts are better than one. J Thorac Cardiovasc Surg 1999;117:855–72. 21. Edmunds LH Jr, Hessell EA, Colman RW, Menasche P, Hammon JW Jr. Extracorporeal circulation. Introduction. In: Cohn LH, Edmunds LH Jr, eds. Cardiac surgery in the adult. 2nd ed. New York: McGraw-Hill, 2003:316. 22. Gruentiz A. Transluminal dilation of coronary artery stenosis. Lancet 1978;1:263. 23. Mack MJ, Brown PP, Kugelmass AD, et al. Current status and outcomes of coronary revascularization 1999-2002. Sur-
GIBBON’S HEART-LUNG MACHINE MACK ADVANCES IN TREATING CAD
24.
25.
26.
27.
28. 29. 30. 31.
32.
33.
34.
35.
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gical and percutaneous procedures. Ann Thorac Surg 2003 (In press). Benetti F, Mariani MA, Sani G, et al. Video-assisted minimally invasive coronary operations without cardiopulmonary bypass: a multi-center study. J Thorac Cardiovasc Surg 1996;112:1478 –84. Reichenspurner H, Gulielmos V, Wunderlich J, et al. Portaccess coronary artery bypass grafting with the use of cardiopulmonary bypass, and cardioplegic arrest. Ann Thorac Surg 1998;65:413–9. Dewey TM, Mack MJ. Myocardial revascularization without cardiopulmonary bypass. In: Cohn LH, Edmunds LH Jr, eds. Cardiac surgery in the adult. 2nd ed. New York: McGrawHill, 2003:609. Diegler A, Spyrantis N, Matin M, et al. The revival of surgical treatment for isolated proximal high-grade LAD lesions by minimally invasive coronary artery bypass grafting. Eur J Cardiothorac Surg 2000;17:501. Jansen EW, Lahpor JR, Borst C, Grundeman PF, Bredee JJ. Off-pump coronary bypass grafting: how to use the Octopus tissue stabilizer. Ann Thorac Surg 1998;66:576 –9. Connolly MW. Current results of off-pump coronary artery bypass surgery. Semin Thorac Cardiovasc Surg 2003;15:45– 51. Mack MJ. Beating heart surgery: does it make a difference? Am Heart Hosp J 2003;1:149 –57. Angelini GD, Taylor FC, Reeves BC, et al. Early and midterm outcomes after off-pump and on-pump surgery in Beating Heart Against Cardioplegic Arrest Studies (BHACAS 1 and 2): a pooled analysis of two randomized controlled trials. Lancet 2002;359:1194 –9. van Dijk D, Nierich AP, Jansen EWL, et al. Early outcome after off-pump versus on-pump coronary bypass surgery: results from a randomized study. Circulation 2001;104: 1761–6. Puskas JD, William WH, Duke PG, et al. Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay. A prospective randomized comparison of two hundred unselected patients undergoing off-pump versus conventional coronary artery bypass grafting. J Thorac Cardiovasc Surg 2003;125:797–808. Society of Thoracic Surgeons. STS national database executive summary. Available at: http://ctsnet.org/file/ stsnationaldatabasefall2002executive summary.pdf. Accessed 22 January 2003. Mueller XM, Jegger D, Augstburger M, Horisberger J, Godar G, von Segesser LK. A new concept of integrated cardiopulmonary bypass circuit. Eur J Cardiothorac Surg 2002;21: 840 –6.
SUPPLEMENT
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