Vein Graft Stenosis

Article Author:
Pedro Valdes
Article Editor:
Miguel Diaz
Updated:
3/5/2019 5:23:31 PM
PubMed Link:
Vein Graft Stenosis

Introduction

The long-term patency and success of saphenous venous grafts in coronary artery bypass graft surgery (CABG) remains a challenge due to their accelerated atherosclerosis rates as well as multifactorial causes of graft failure. 

Venous graft bypass procedures have been practiced for over a century, and are not yet perfected. In 1906, Goyanes inserted the first autogenous vein graft into a human, using a popliteal vein as an interposition graft to bridge an arterial defect, following excision of a syphilitic popliteal aneurysm. By 1962, the development of selective coronary angiography allowed Sabiston to perform the first right coronary artery bypass procedure. The art of coronary artery bypass grafting was further developed and refined by Garret and Favaloro.[1][2][3][4]

Etiology

Clinical graft patency of autogenous saphenous vein grafts in the arterial circulation can be divided into three temporal categories: early (0 to 30 days), short-term (30 days to 2 years) or long-term (greater than 2 years). Early failures are ascribed to technical failures occurring at the anastomoses, the position of the graft, kinking of the graft, or initial poor distal runoff and account for less than 5% of all vein graft occlusions. Studies of human veins harvested for bypass procedures have revealed that many have abnormal histologic and physiologic attributes. Furthermore, the quality of the saphenous vein can have significant clinical consequences. Vein grafts in the arterial circulation must be considered as a viable, constantly adapting and evolving conduit.[5][6][7][8]

Epidemiology

Given that over 300,000 patients undergo CABG in the United States each year, the burden of the saphenous venous graft (SVG) failure on our healthcare system is of significant concern. More than one CABG procedure is performed per 1,000 adults per year in the United States alone. Early occlusion, before hospital discharge, has been reported to occur in 8% to 12% of venous grafts. During the first year after CABG, upwards of 15% to  30% of SVGs are occluded, and about half of all patients develop SVG failure in greater than 1 graft within 10 years after surgery. After the first year post-CABG, the annual occlusion rate is about 2%, and it rises to approximately 4% annually between postoperative years 6 and 10. Patency rates with internal mammary grafts are superior. Late patency of grafts is related to coronary arterial runoff as determined by the diameter of the coronary artery into which the graft is inserted, the size of the distal vascular bed, and the severity of coronary atherosclerosis distal to the site of insertion of the graft. The highest graft patency rates are found when the lumina of vessels distal to the graft insertion are larger than 1.5 mm in diameter and perfuse a large vascular bed.

Pathophysiology

The wall of a vein is traditionally divided into three anatomic layers: the intima, the media, and the adventitia.  Veins are highly compliant over the range of venous pressures and are relatively noncompliant at arterial pressures. Veins have a high degree of lactic dehydrogenase activity with lesser amounts of the other oxidative enzymes. Although there is no difference in total protein content, the amount of collagen appears to be greater in the saphenous veins. The total content of glycosaminoglycans is also similar in the saphenous veins and internal mammary arteries, although the major component present in the internal mammary artery is heparin sulfate while in the saphenous vein, dermatan sulfate is the dominant glycosaminoglycan. There are differences in the vasomotor function of the saphenous veins compared to the internal mammary arteries. Nitric oxide and prostacyclin-mediated relaxation responses of saphenous veins are much less, and the maximal contractile forces generated are much greater than the internal mammary artery. In addition, local angiotensin-converting enzyme activity, which converts angiotensin I to angiotensin II and degrades bradykinin (a potent mediator of nitric oxide release), is greater in the saphenous vein compared to the internal mammary artery. Saphenous veins demonstrate a spectrum of pre-existing pathological conditions ranging from significantly thickened walls to post phlebitic changes and varicosities at the time of harvest. Between 2% and 5% of these veins are unusable, and up to 12% can be considered "diseased."  These diseased veins have a patency rate one-half that of "non-diseased" controls.

Perioperative manipulations of veins before their insertion have been shown to produce significant tissue damage. Such implantation injury leads to endothelial dysfunction, endothelial cell injury, endothelial denudation, and smooth muscle cell injury. Each is an important factor in the initiation of intimal hyperplasia. Postoperative venous grafts, following exposure to the arterial environment the cells experience severe stretching and increased tangential stress, both of which contribute to endothelial cell damage. In addition, there is extensive subendothelial edema which reflects a combination of increased transmural flux and stretches damage due to the vein graft's distension by arterial blood pressure. Histological surveys of human saphenous vein grafts have been derived from specimens obtained at autopsy or at re-operation. Vein grafts obtained in the early postoperative period (less than 24 hrs) show focal loss of endothelial cells particularly at the perianastomotic areas and fibrin deposition on the intima.

Intimal hyperplasia is the universal response of a vein graft to insertion into the arterial circulation and is considered to result from both the migration of smooth muscle cells out of the media into the intima and proliferation of these smooth muscle cells. Macroscopically, intimal hyperplastic lesions appear pale, smooth, firm and homogenous; they are uniformly located between the endothelium and the medial smooth muscle cell layer of a vein graft.  The majority of VGS from human peripheral bypass grafts can be classified as intimal hyperplasia. They are highly cellular, consisting predominantly of smooth muscle cells with a variable amount of connective tissue features similar to the intimal hyperplasia of animal models. During the initial perioperative period after saphenous vein coronary grafting, early stenosis and occlusions occur in 5% to 8% of grafts due to intimal hyperplasia. Recent evidence suggests that deformation of smooth muscle cells by arterial hemodynamics can lead to activation of protein tyrosine kinases and thereby initiate smooth muscle cell proliferation. Vein grafts with lower flows are associated with greater intimal thickening. Similarly, low shear stress is also associated with increased development of intimal hyperplasia in vein grafts.

Hypertension in both human and experimental models does not affect the development of intimal hyperplasia in the short- or long-term. Furthermore, it appears that hypertension is not associated with the later development of vein graft atherosclerosis. On the other hand, clinical studies have shown an association of hyperlipidemia with the development of intimal hyperplasia/atherosclerosis and with higher vein graft failure rates. Clinically, diabetes does not appear to impact significantly on vein graft patency, but experimentally, it does increase short-term intimal hyperplasia development. In cases of combined hypertension and hyperlipidemia, there appear to be no additive effects on intimal hyperplasia development in vein grafts compared to hyperlipidemia alone. In contrast, however, the combined presence of diabetes and hyperlipidemia has a significant additive effect on the formation of intimal hyperplasia in experimental vein grafts. Under hyperlipidemic conditions, venous tissue has demonstrated an avidity for the uptake of serum lipid, surpassing that of arterial tissue in the same species. Intimal hyperplastic lesions of experimental hypercholesterolemic vein grafts are composed predominantly of lipid-laden smooth muscle cells with macrophages in various stages of foam cell formation interspersed between these cells.  Macrophages are one of the principal cells involved in the development of atherosclerosis through the oxidation of lipoproteins and the formation of lipid peroxides. Reduction of both cholesterol and low-density lipoproteins is considered useful in slowing and preventing atherogenesis.

Histopathology

Vein grafts retrieved from patients with angiographic evidence of occlusive disease demonstrate histologic features of atherosclerosis. The earliest these lesions have been seen is 6 months after implantation. Thus, it appears that these late occlusions of vein bypass grafts are due to the development of a rapidly progressive and structurally distinct form of atherosclerosis which has been termed "accelerated atherosclerosis" to distinguish it from "spontaneous atherosclerosis." Accelerated atherosclerosis is morphologically different to spontaneous atherosclerosis in that its lesions appear to be diffuse, more concentric, and have a greater cellularity with varying degrees of lipid accumulation and mononuclear cell infiltration. The syndrome of accelerated atherosclerosis shares many of the pathophysiological features of intimal hyperplasia, however, the prime mediators of this type of atherosclerosis are likely to be the macrophage. In addition, the endothelium overlying accelerated atherosclerotic lesions expresses the class II antigens which are not observed in spontaneous atherosclerosis.

History and Physical

Patients presenting with VGS will present with symptoms of typical angina. Depending on the time frame of when the vein graft has failed, patients may begin to experience chest pain or pressure-like sensation over their chest with minimal to no exertion. Symptoms of ischemia also may include but are not limited to shortness of breath, palpitations, generalized weakness, diaphoresis, nausea, and epigastric discomfort.

Physical exam findings while evaluating patients with ongoing ischemia include sweaty, clammy, and possibly cool skin; abnormally elevated jugular venous pulse; rales on lung auscultation; possible S3 or S4 on cardiac auscultation; and possible bilateral, lower extremity edema.

Evaluation

During evaluation for possible cardiac ischemia from an occluded vein graft, a 12 lead EKG is essential. Comparison with previous EKGs should be made and assessed for new bundle branch blocks, significant ST deviations, and possible T wave abnormalities. Laboratory evaluation also should be included in the assessment for ischemia, and this includes cardiac troponin levels, Creatine kinase-MB, and brain natriuretic peptide (BNP) or pro-BNP levels. A basic chest x-ray will not show any evidence of vein graft occlusion, but in the case of new-onset congestive heart failure due to ischemia, it will display cardiomegaly and pulmonary congestion. Pulmonary findings on chest x-ray include vascular redistribution, interstitial edema (Kerley line), and alveolar edema (cotton wool appearance). Lastly, a 2D echocardiogram also can be assessed for significant drops in ejection fraction as compared to previous echocardiographic studies, new wall motion abnormalities, and significant valvular regurgitation from malfunctioning papillary muscles. 

Treatment / Management

As for bare metal stent (BMS) versus covered versus drug-eluting stent (DES) treatment, these have all been evaluated. The SAVED (Saphenous Vein de Novo) trial reported that compared with balloon angioplasty, BMSs were associated with higher procedural success, a trend toward a reduction in angiographic restenosis, and lower MACE through 240 days. SYMBIOT III (A Prospective, Randomized Trial of a Self-Expanding PTFE Stent Graft During SVG Intervention–Late Results) compared the self-expandable PTFE-covered nitinol Symbiot stent with BMS. At 8 months, the incidence of MACE between the Symbiot group and BMS was similar. A trend toward increased target lesion revascularization with the Symbios stent was also observed. The RRISC (Reduction of Restenosis in Saphenous Vein Grafts With Cypher Sirolimus-Eluting Stent) trial, which included 75 patients, reported that sirolimus-eluting stents reduced late loss, the binary restenosis rate, and target lesion and vessel revascularization compared with BMS at 6-month follow-up. A meta-analysis comparing DES with BMS in SVG intervention also has reported lower mortality, MACE, target lesion revascularization, and target vessel revascularization without increased risk of myocardial infarction or stent thrombosis when utilizing DES for SVG interventions.[9][10][11][10]

Complications

A recognized consequence of SVG intervention is distal embolization of atheroembolic debris with decreased epicardial and microvascular perfusion due to capillary plugging and vasospasm from the release of neurohumoral factors such as serotonin. Slow- or no- reflow phenomenon can be seen in approximately 10% to 15% of cases of SVG graft interventions and is associated with periprocedural angina and ischemic ST-segment changes. In these instances, myocardial infarction occurs in 31% of patients and in-hospital mortality increases 10-fold. Embolic protection devices are associated with periprocedural myocardial infarction rates of less than 10%. After SVG intervention, the length of the lesion, greater of SVG angiographic degeneration, and larger estimated plaque volume can predict 30-day major adverse cardiac events (MACE). Sex disparities also exist when it comes to SVG graft interventions as women have higher 30-day cumulative mortality rates compared with men. Furthermore, women tend to have a higher incidence of vascular complications and post-procedural acute renal failure. In a 172-patient study of SVG intervention with DESs, the only significant predictor of 1-year MACE was chronic renal insufficiency (serum creatinine  1.5 mg/dL). Also, overall mortality rates were greater in patients with renal insufficiency.

Pearls and Other Issues

When performing percutaneous interventions on saphenous vein occlusions, there is always a risk of downstream embolization of atherothrombotic debris as well as risk of no-reflow phenomena. It is recommended by the ACC/AHA guidelines to use embolic protection devices when feasible. If and when no-reflow occurs, there are a variety of medications that can help prepare the microvasculature to receive distal embolization debris including adenosine, nitroprusside, verapamil, and nicardipine. When diseased SVGs cause progressive ischemic syndromes, a percutaneous coronary intervention of the native coronary arteries should be considered whenever possible.

Enhancing Healthcare Team Outcomes

Patients post CABG are followed by the nurse practitioner, primary care provider, the cardiologist, cardiac surgeon, and the internist. When vein graft stenosis is diagnosed, there are two treatment options- REDO surgery which is a major undertaking or PCI. With advances in PCI, it appears that vein graft stenosis can be managed with stenting provided precautions are taken to prevent emboli. Short term results are good and devoid of the morbidity of open heart surgery.[12][13] (Level II)


References

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