—  SHORT COURSE #57  —

Atherosclerosis: Practical Implications for Pathologists

Section 5 - Coronary Artery Bypass Grafts

Jagdish Butany
John Veinot


Case #4:
This 47-year-old male had a myocardial infarction at age 39 years. Investigations showed that this heavy smoker had hyperlipidemia, hypertension and diabetes mellitus. He was not a lightweight. At age 41 years, he once again developed chest pain and was investigated. He had three vessel CAD and underwent CABG with three vein grafts (RCA, intermediate and OM1) and a left internal thoracic artery graft to the LAD. He had recurrent episodes of congestive heart failure necessitating hospitalization. He underwent orthotopic heart transplantation. His explanted heart was available for review.

Coronary Artery Bypass Grafts:
With over a half a million coronary artery bypass graft operations performed in North America alone,for myocardial revascularization, coronary artery bypass grafts remain the most frequently performed surgical procedure, worldwide. They also therefore account for the largest amount of resources used in cardiovascular medicine, certainly more than other single procedure. The average cost of such a procedure, was $45,000, about ten years ago. Today, it must be much more. The operative mortality associated with coronary artery bypass surgery in all comers is about 2%. First time elective surgery in patients with a grade II or III ventricle is, in many centers, is less than 1.6%. Outcomes are somewhat worse for emergent procedures and the consistent predictors of mortality after coronary artery bypass surgery are emergent or urgent surgery, patient's age, previous cardiac surgery, female sex, a poor left ventricular rejection fraction, degree of stenosis and the number of foci of such stenosis of the left main coronary artery and the number of arteries stenosed. The history of angina pectoris, ventricular arrhythmias, congestive heart failure, mitral valvular incompetence, obstructive lung disease, diabetes mellitus, renal dysfunction are all other comorbid factors which worsen the morbidity and mortality.

Metanalysis of randomized trials of coronary artery bypass graft vs. medical therapy show that the CABG group does have a lower mortality and morbidity than the medically treated group at five and ten years with a 39 and 17% risk reduction respectively. [36]

A quick look at coronary artery surgery lists shows that more than 10% of cases and in some institutions 15 - 20% of cases are redo coronary artery bypass graft procedures( these numbers appear to be changing -downward , at least at our center. Perhaps more of the patients are getting stents in their bypass grafts and in the native vessels.. The indications for re operation include worsening of native coronary artery disease, inadequate revascularization and graft failure (early as well as late). The mortality for redo surgery is higher, at 2 - 10%.

Over 1 million coronary artery bypass grafts are performed worldwide annually. Of these, over half are performed in the United States, significant numbers in the other Western countries and increasing numbers in the developing countries. A heavy price to pay for playing catch-up with regard to industrial development! The principle surgical approach to the therapy of ischemic heart disease / coronary artery disease has been direct revascularization. Studies show improved survival amongst cohorts of surgically treated patients when compared to those treated medically or those treated with percutaneous, transluminal interventions. It is important to remember that in the recent past (close to three decades now), improvements in surgical technique, equipment and coronary perfusion have improved survival, decreased morbidity, decreased mortality from coronary artery bypass graft surgery (performed the first or second time. Significantly improved anesthesia and post-operative care, has reduced the length of time patients spend in hospital after surgery.

With the more recent improvement and increased availability of less invasive techniques for coronary artery bypass graft surgery, surgeons are able to provide direct revascularization or bypass grafts to patients whose medical conditions would in the past, have prohibited the standard open approach to cardiopulmonary bypass.

History:
Prior to the development of coronary artery bypass graft surgery (CABG), several innovative techniques were used to "improve" blood flow to the ischemic myocardium. Some were probably partly successful but most were not and all have since been abandoned at least in their original forms. [9, 10, 11] The Vineberg procedure is by far the precursor of today's direct revascularization and it entailed the implantation of the internal thoracic artery into a tunnel in the myocardium on the anterior surface of the left ventricle [11].

Coronary artery arteriography or cinecoronary arteriography by Sones and Shirey of the Cleveland Clinic in the late 1950's provided the foundation for coronary artery bypass graft surgery (CABG). Angiography permitted the accurate placement of CAB grafts. In these initial studies, the mortality rate was 12%, with massive improvement over previously mortality rates, of nearly 50%.

The next advancement was the introduction of direct anastomoses of the left internal thoracic artery (LITA) to the LAD [12]. The long-term efficicacy of cardiac revascularization is established by three randomized studies. The European study of 768 randomized men, followed up to eight years, showed that survival was significantly improved in patients with significant three-vessel disease and in patients with significant stenosis of the proximal LAD Ca. As compared with medically treated patients, late mortality was reduced by 53% after five years and amongst those patients with three-vessel disease, the five-year mortality was lower by 66%. The patients with significant disease of the proximal LADCa, five-year mortality were diminished by 50%, by surgery.

The Veteran's Administration long-term CABG survival study in 686 patients having stable angina followed for an average of 11.2 years. The seven-year survival showed a statistically significant survival benefit of 77% with surgical therapy compared with 70% survival with medical treatment. This benefit diminished by eleven years of observation but a survival advantage persisted eleven years in surgical patients with three-vessel disease and impaired left ventricular function and in those with high clinical risk defined by pre-operative ST segment depression. The coronary artery surgery study (CASS) showed survival data on 780 patients with stable angina and ejection factions greater than 35%, assigned to receive medical or surgical therapy. At eight years follow-up, 87% of the surgically treated patients were alive as compared with 84% of those receiving medical therapy. While this was not statistically significant, the trend favored surgical therapy. The benefits of direct revascularization surgery - CABG - decreased progressively with time. This is due primarily to the development of disease in the saphenous vein graft, resulting in gradual stenosis and ultimately occlusion of the vein grafts.

The left internal thoracic artery (LITA) grafts appear to be "resistant" to atherosclerosis and the improved late patency of these bypass grafts improves the patient's survival. Today, many other vessels such as the right internal thoracic artery (RITA), radial artery and the gastroepiploic artery are available or are being used for vascular bypass grafts to coronary arteries.

Minimally Invasive Approaches :
In recent years, coronary artery bypass procedures have been performed using alternate incisions with and without cardiopulmonary bypass. In all cases, cardiopulmonary bypass is available as an option, should the need arise. Minimally invasive techniques are used to reduce morbidity of surgery and permit early hospital discharge, as well as to avoid the difficulties associated with a sternotomy and the cosmetic difficulty of a long mid chest incision! Today, minimally invasive direct coronary artery bypass graft procedures are proposed as alternatives to percutaneous transluminal coronary angioplasty (PTCA) for single vessel disease of left anterior descending coronary artery. The heart is exposed through a 10.0 cm transverse parasternal incision and a bypass is created from the LITA to the LAD directly or with an interposed segment of inferior epigastric artery or radial artery. A variety of techniques are used to help make the anastomosis with the beating heart.

OPCAB Surgery - Off Pump Coronary Artery Bypass :
This procedure is performed using a standard median (middle) sternotomy and access to coronary artery is achieved by accurate placement of pericardial stay sutures to rotate and lift the heart. A relatively bloodless field is obtained and pedicle arterial grafts used for bypass. This procedure is believed to reduce the incidence of stroke and other organ injury caused by embolization of atherosclerotic debris. These pedicle arterial grafts, allow a no-touch technique with regard to the aorta.

The availability of sutureless connectors for the proximal anastomosis was supposed to allow for allow for easier aorto-saphenous vein graft proximal anastomosis. These are not particularly effective and their use has not gained significant momentum.

Graft Patency:
There are many reports about long-term data regarding coronary artery bypass grafts. Rahimtoola et al reporting on procedures performed between 1974 and 1988 (n=7026) reported a 2.1% operative mortality and a 10 and 15-year survival probability of 74 +/- 1 and 55 +/- 2% respectively [13]. Sarjeant et al reported a series of 9600 patients followed for up to 20 years. Freedom for re -intervention at one, ten and fifteen years were 99, 89 and 72% respectively. They concluded that patients were "relatively free of the need for intervention for the first decade after coronary artery bypass surgery". Approximately 50% of patients surviving more than ten years required reintervention [14]. From most studies, the patency rate for saphenous vein bypass grafts ranges from 40 to 50% at ten years. The patency rates of various free or pedicled arterial conduits is lessestablished.

3. Complications:The important perioperative complications are stroke, wound infection, myocardial infarction and graft thrombosis. Stroke includes permanent stroke and transient ischemic attacks, as well as delirium. Permanent neurologic deficits ranges from 0.8 to 5.2% and the mortality associated with this may be as high as 38%. Surgery for coronary artery disease has "come of age" over the past 25 years. Direct revascularization means predictable relief of angina and improved quality of life, in 80 to 90% of patients. Patient survival is improved. The use of multiple arterial grafts in revascularization, should improve patient outcomes even further both, regarding graft survival and quality of survival.

With the use of different types of bypass grafts on the same hearts , it is interesting to see and note the type and degree of change in the bypass graft in the same individual and ofcourse the same heart.

Case 4 a: This 45 year old came to heart transplantation , 3 years after having undergone CABG (X3) with a LITA to the LAD, a free radial graft to the OM and an SVG to the RCA.

The findings will be discussed briefly.

References

Atherosclerosis
  1. Murray CJ, Lopez AG. Global Mortality, Disability and Contribution of Risk Factors: Global Burden of Disease Study. Lancet 1997;349:1426-42

  2. Poole J, Florey HW. Changes in the endothelium of the aorta and the behaviour of macrophages in experimental atheroma-of rabbits. J Pathol Bacteriol 1958; 75:245-52).

  3. Ross R, Glomcet JA, Kariya B, Harker LA. A platelet dependency serum factor that stimulates the proliferation of smooth of arterial cell muscle cells in-virto. Proc Natl Acad Sci USA. 1974; 71: 1207 - 11.)

  4. Brown MS, Goldstein JL. A receptor medicated pathway for cholesterol hemostasis. Science 1986; 272: 265 - 8)

  5. Breslow JL. Mouse models of atherosclerosis. Science 1996; 272: 685-8.

  6. Gimbrone MA, Mago T, Topper JM. Biomechanical activation: An emerging paradigm in endothelial adhesion biology. J Clin Invest 1997; 100: S61-5).

  7. Kovenen PT, Kaartinen M, Paavoen T. Infiltrates of activated mast cells at the site of coronary atheromatous erosion or rupture in myocardial infarction. Circulation 1995; 92: 1084 - 8.)

Coronary artery interventions
  1. Van der wal AC, Becker AE, Van der loos CN, Das PK. Site of intimal rupture or erosion of thrombosed coronary atherosclerotic plaques is characterized by an inflammatory process irrespective of the dominant plaque morphology. Circulation 1994; 89: 36 - 44.)

  2. Senning A. Strip grafting and coronary arteries. J Thorac Cardiovasc Surg 1961; 41: 542 - 9.)

  3. Semp K, Udwai TE, Kinare SG, Parulkar GB. Transmyocardial acupuncture: A new approach to myocardial revascularization. J Thorac Cardiovasc Surg 1965; 50: 181 - 9).

  4. Weinberg A, Bullard W. Technical factors which favor mammary - coronary anastomosis: Report of 45 cases of human coronary artery disease, thus treated. J Thorac Surg 1955; 30: 411-31).

  5. Kolessov VI. Mammary artery - coronary artery anastomosis as methods of treatment for angina pectoris. J Thorac Cardiovasc Surg 1967; 54: 535-44.)

  6. Rahimtoola SH, Fessler CL, Grunkemeier GL et al. Survival 15 to 20 years after coronary bypass surgery for angina. J Am Coll Cardiol. 1993; 21: 151-7

  7. Segreant P, Blackstone E, Meyns B, Stockman B, Jashari R. First cardiological or cardiosurgical re-intervention for ischemic heart disease after primary CABG. Eur J Cardiothorac Surg 1998; 14: 480 - 7

PCI-Angioplasty and stents
  1. Gruentizg AR, King SC, Schlumpf M, et al. Long-term follow up after percutaneous transluminal coronary angioplasty. The early Zurich experience. N Eng J of Med 316: 1127 - 1132, 1987.

  2. Fishman DL, Leone MB, Bain DS et al. A randomized comparison of coronary - stent placement and balloon angioplasty and the treatment of coronary artery disease. Stent restenosis study investigators. N Engl J of Med; 331: 496 - 501,1994.

  3. Cutlip DE, Chauhan MS, Bain DS, et al. Clinical restenosis after coronary stenting: Respective from multicenter clinical trials. J Am Col Cardiol 40: 2082 - 2089, 2002

  4. Isles CG, Robertson S, Phil D: Management of renal vascular disease: A review of renal artery stenting in ten studies. QJN 92: 159 - 167, 1999.

  5. Lee ES, Steenson CE, Trimble KE, et al. Comparing patency rates between external iliac and common iliac artery stents. J Vasc Surg 31: 889 - 894, 2000

  6. Farb A, Sangiorgi G, Carter AJ, et al. Pathology of acute and chronic coronary stenting in humans. Circulation 99: 44 - 52, 1999.

  7. Reference: Barth KH, Virmani R, Frolich J, et al. A comparison of vascular wall reactions to Palmaz stents, Strecker Tamplin stents and Wall stents in canine iliac and femoral arteries. Circulation 93: 2161 - 2169, 1996.

  8. Ajani AE, Kim HS, Waksman R. Clinical trials of vascular brachytherapy for in-stent restenosis update. Cardiovascular Radiation Medicine 2001; 2: 107 - 103.

  9. Hansrani N, Overbeck K, Smout J et al. Intravascular brachytherapy: A systematic review of its role in reducing restenosis after endovascular treatmenin peripheral arterial disease. European Journal of Vascular and Endovascular Surgery 24: 377-382, 2002.

Stents and Drugs
  1. De Scheerder I, Wang K, Wilczec K et al. Local methylprednisolone inhibition offoreign body response to coated intracoronary stents. Coronary Artery Disease. 1996; 7: 161 - 166.

  2. Jordan MA, Toss RJ, Wilson L. The mechanism of mitotic block and inhibition ofcell proliferation by paclitaxel at low concentration. Proc Nat Acad Sci. USA, 1993, 90: 9552-6.

  3. Farb A, Haller PS, Carter JA. Paclitaxel polymer-coated stents reduce neointima. Abstract. Circulation 1997: 96 suppl 1: 609.

  4. Drachman DE, Edelman ER, Seifret P, et al. Neointimal thickening after stent delivery of: paclitaxel change in composition and arrest of growth over six months. J Am Coll Cardiol 2001; 36: 2325 - 32

  5. Heldman AW, Cheng L, Jenkins GM, et al. Paclitaxel stent coating inhibits neointimal hyperplasia at four weeks in a post angioplasty model of coronary restenosis. Circulation 2001; 103: 2289 - 95
  1. Fajadet A. Morice MC. Bode C etal. Maintainance of long-term clinical benefit with Sirolimus eluting coronary stents: 3 year results of RAVEL trial. Circulation.111:1040-44.2005.
  1. Svensson LG: Natural history of aneurysms of the descending and thoracoabdominal aorta. J Card Surg 12(suppl); 279-284, 1997

  2. Crawford ES, De Natale RW. Thoracoabdominal aortic aneurysms: Observations regarding the natural course of the disease. J Vasc Surg 3: 578-582, 1986

  3. Cooley DA. The history of surgery of the thoracic aorta. Cardiol Clinic 70: 609 - 613. 1999.

  4. Cosellie JS, Lemiere SA, Miller CC, et al. Mortality and paraplegia after thoracoabdominal aortic aneurysm repair: A risk factor analysis. Ann Thorac Surg 69: 409-414, 2000

  5. Parodi JC, Palmaz JC, Barone HD. Transfemoral interluminal graft implantation for abdominal aortic aneurysm. Am Vasc Surg 5: 49 - 59. 1991

  6. Dack MD, Miller DC, Semba CP, et al. Transluminal placement of endovascularstent grafts for the treatment of ascending thoracic aortic aneurysms. New England Journal of Medicine 33: 1729 - 1734, 1994

  7. Parodi JC. Endovascular stent graft repair of aortic aneurysms. Curr Opinion in Cardiology 12: 396 - 405. 1997).

  8. Zucker D, Paduzzi P, et al: Effect of coronary artery bypass graft surgery onsurvival: Overview of ten year results from randomized trials by the coronary artery bypass graft surgery trialists collaboration. Lancet 344: 563, 1994).

Aortic Stent Grafts
  1. Parodi JC. Endovascular repair of abdominal aortic aneurysms and other arterial lesions. J Vasc Surg 21; 549 - 556, 1995).

  2. Dorros G, Parodi J, Schonholz C, et al. Evaluation of endovascular abdominalaortic aneurysm repair: Anatomical classification, procedural success, clinicalassessment and data collection. J Endo Vasc Surg 4: 203 - 211, 1997).

  3. Ernst CB. Present therapy for infrarenal aortic aneurysms. N Engl J Med 336: 591997.

General
  1. Lusis AJ, Fogelman AM, Fonorov GC. Genetic Basis of Atherosclerosis (Part 1)New genes and Pathways.Circulation ; 110:1868-1873. 2004.

  2. Houner H.Occurrence of diabetes mellitus in Germany(in German). Dsth Med Wochenschr 123: 777-82.1998.

  3. Stamler J et al.Diabetes,other risk factors and 12 year cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial.Diabetes Care; 16:434-44.

  4. Marso P et al.Optimising the percutaneous interventional outcomes for patients with diabetes mellitus: results of the EPISTENT. Circulation 100:2477-84:2000.

  5. Tiong A. Y,Brieger D. Inflammation and coronary artery disease.Am H J:150:11-182005

  6. Willerson J, Kereiakes D. Endothelial dysfunction. Circulation 108:2060-1.2003.

  7. Springer T. A. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multi step paradigm. Cell76:301-14.1994.

  8. Cleland J, Loh P, Freemantle N et al. Clinical trials update from the European Society for Cardiology:SENIORS.ACES.PRIOVE_IT.ACTION.and the HF-ACTION trial Eur J Heart Fail 6:787-91.2004.

  9. Ridker P,Brown P,Vaughn D et al.Established and emerging plasma biomarkers inthe prediction of first atherothrombotic events. Circulation109(Suppl):6-19.2004.

  10. Rankin JM,Spinelli JJ,Carrere RG et al. improved clinical outcome after widespread use of coronary artery stenting in Canada. N Engl J Med .341:1957-65.1999.

  11. Kuntz RE, Rogers C, Baim DS .Percutaneous coronary intervention-induced emboli during primary PC I for STEMI: Too little, too much, or too late? Am Heart J.150: 4-6.2005.

  12. Al Suwaidi J,Berger PB. Do stents reduce mortality compared to balloonangioplasty? A critical review of all the evidence. Am Heart J.150:7-10.2005

New References

Atherosclerosis:
  1. Napoli C et al.. Rethinking primary prevention of atherosclerosis- related diseases. Circulation.2006. 28;114:2390-27

  2. Tofler GH & Muller JE.Triggering of acute CV disease and potential preventive strategies.Circ.2006.24: 114(17):1863-72.

  3. Semenkovitch CE. Insulin resistance and atherosclerosis. J Clin Invest, 2006;116:1813-22.

  4. Lucas AR et al. Inflammation in atherosclerosis: some thoughts about acute coronary syndromes. Circ '06;113(17):e728-32.

  5. Goldschmidt-Clermont PJ et al. Atherosclerosis 2005: recent discoveries and novel hypotheses. Circulatiion 05;112(21):3348:-53.

  6. Libby P,Theroux P.Pathophysiology of coronary artery disease.Circulation '05 111(25):3481-8.

  7. Davignon J, Ganz P. Role of Endothelial dysfunction in atherosccclerosis.Circ '04;(23Suppl)L 111) 27-32.

Bypass Grafts:
  1. Hochman JS,Steg PG, Does preventive PCI work? (Editorial),NEJM 10;1056.

  2. Martens TP et al. New technology for surgical coronary revascularization.Circ '06; 114(6):606-14.

  3. Verma S et al.Shold radial arteries be used routinely for CABG ? Circulation '04;110(5):240-6.

Stents (coronary):
  1. Hochman JS,Steg PG, Does preventive PCI work? (Editorial),NEJM 10;1056

  2. Boder WE et al;Optimal medical therapy with or without PCI for Stable Coronary Disease. NEJM 10.1056. ( COURAGE Trial)

  3. Khot UN et al. Radial artery bypass grafts have an increased occurrence of angiographically severe stenosis and occlusion compared with the left internal mammary arteries and saphenous vein grafts. Circulation'04;109(17):2086-91.

  4. Ligthart S et al.The cost-effectiveness of Drug eluting stents: a systematic review.CMAJ '07;176(2):199-205.

  5. Keriakis DJ et al.Lt main coronary revascularization at the crossroads.Circ '06;113(21):2480-4.

  6. Anis KK et al.The future of Drug eluting stents.Heart '06;9295):650-7.

  7. Butany J et al.Coronary artery stents: identification and evaluation. J Clin Pathol 05; 58:795-804.

Aortic stent Grafts:
  1. Endovascular Stent Grafting of descending aortic aneurysms. Chest'03;124(2):714-9.

Ventricular Assist Devices:
  1. Stevenson LW et al. Left ventricular assist devices:bridges to transplantation, recovery, and destination for whom? Circulation '03; 108(25):3059-63.

  2. Mancini D et al'Mechanical device -based methods of managing and treating heart failure.Circulation '05;112(3);438-48.

  3. Copeland JG et al. Caarduac replacement with a total artificial heart as a bridge to transplantation. NEJM '04:351 (9):859-67.