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Arteriosclerosis
Arteriosclerosis By CHARLES T. DOTTER, M.D.
E
VEN AT THE RISK of putting some unwanted punch into the threatened population explo,sion, the conquest of arteriosclerosis amounts to medicine’s moist important unfinished business. Barring nuclear catastrophe, environmental toxification, and possibly the SDS, it is a statistical near-certainty that the subject of this chapter will sooner or later do in most of its readers! GENERAL NATURE OF ARTERIOSCLEROSIS/ATHEROSCLEROSIS
It is next to impossible to say anything noncontroversial about the basic nature of arteriosclerosis. Experts who, by virtue of their special interest and scientific experience, should know most about it, seem to be least agreed as to what it is, what causes it, how to treat it, and even what to call it. A.s to the semantics, regardless of whether you call it arteriosclerosis or atherosclerosis, a few will take issue, but nearly everyone will know what y-ou mean. With res’pect to etiology, abnormal plasma lipids, dietary habits, inherited metabolic defects, emotional states, sticky platelets, too much fibrin, too little fibrinolysis, hypertension, diabetes, the sedentary life, and smoking have all been blamed for atherogenesis. To add to the confusion (mine anyway), opinions and research on the issue appear to have suffered the consequences of po,larization and partisansship. No doubt influenced by a background in angiography, I take a pragmatic, essentially morphologic approach to atherosclerosis, sharing Fulton’s view that lipid accumulation is a result rather than a cause: o’f early intimal thickening and that progressive luminal narrowing comes about through the repeated deposition of platelets and fibrin and their subsequent conversion into the familiar atherosclerotic lesion.” While the foregoing concept of atherogenesis is certainly not universally accepted, even the Friends of Beta Lipoproteins concede the importance of thrombosis at the time of final luminal obliteration. Here the role of the coagulation mechanism is more apparent than during earlier phases of atherogenesis, perhaps because complete occlusion favors frank thrombosis and alters the atherogenic conversion process. Often, the clinical consequences of acute final occlusion lead to pathologic examination before there is time for the clot to stop looking like a clot. Whatever the basic mechanism, atherosclerotic luminal narrowing is the result of the progressive replacement of normal intima by a thickened core of inelastic collagenous material ( Fig. 1) . The core is loosely attached to the surrounding, more or less intact, media. Purposeful, if chauvinistic, vascular surgeons refer to this zone of IO~XXattachment as the “plane of endarterectomy.” Better to call it the “periatheromatous cleavage plane,” since it also can be the site of localized subintimal hemorrhage, the route of dissecting aneurysm, This uork uxs suppsrted ly C’SPHS Grant HE 03275-13. CHARLES T. DWTSH, M.D.: Professor and Chairmun, Depzrtment of Radiology, UniversiW of Oregon Medicul School; Stelln ujd Charles Guttman Lahoxtory, Portland, Ore. 97201.
229
ARTFBIOSCLEROSIS
Fig.
l.-Cross
section, atherosclerotic
popliteal
artery,
and a pathway for catheter dissection. When visualized during arteriography, it presents a typical appearance ( Fig. 2). Whereas atheromatous intimal change is usually diffuse, clinically significant obstruction often occurs at particular sites of predilection, such as the adductor hiatus, the carotid and aortic b’ifurcations, and the origins of the renal, celiac, mesenteric, and coronary arteries. The tendency for localized obstruction to develop at points of arterial origin, branching, fixation, etc., suggests that hemodynamic and other forms of mechanical trauma are contributory factors in atherogenesis. Other evidence: atherosclerosis correlates with hypertension; proximal obstruction spares the distal bed; degenerative changes commonly appear at sites of jet impact, in association with congenital and acquired aortic valvular deformities, and as late complicatioSns of vascular surgery. However speculative the connection between localized disease and mechanical factors in atherogenesis, predilective sites of obstruction are so common as to constitute clinical facts of life or death, ARTEHIOGRAPHY
Although symptoms of ischemia bring the patient to his doctor and often suggest what’s wrong, precordial pain doesn’t always mean coronary disease and intermittent claudication doesn’t necessarily indicate the site of the responsible arterial obstruction. Physical examination is often of considerable diagnostic aid, particularly palpation and auscultation of accessible arteries; unfortunately, many important arterial narrcwings can’t be detected in this manner. Segmental blood pressure determinations may show a gradient in the
Fig. 2.-Periatheromatous The lumen of the artery nnclrl,,‘3 nr,n ,P”,A lotor
Pm;nehm.mnotn,,c
/a,,l-rintimal~
rnntrart
cleavage plane, left iliac artery. A. is opacified. B. The lumen remains
material parallels the lateral aspect of the lumen (arrow). C. Two seconds later, the lumen is empty. Contrast material persists in the P~P:IVRU~nl~ne hilt will shol-tlv he washed awav.
2 g
:
ARTERIOSCLEROSIS
231
legs and thus spot a level of obstruction. Ultrasonic and plethysmographic studies are similarly useful indicators of arterial obstruction, if not centrally, at least in the peripheral arteries, While the EKG can be counted upon to reveal myocardial damage or ischemia consequent to impaired coronary flow, it is o’f little value in determining the feasibility of corrective surgery. The roentgen identification and characterization of calcium in arteries aid by revealing probable sites of atheromatous disease, outlining otherwise hidden aneurysms, suggesting the diagnosis of syphilitic aortitis, and disclosing benign medial sclerosis ( Monckeberg’s) , On the other hand, typical atheromatous calcification can be present in the absence of significant hm~inal narrowing, and vice versa. A patient with localized atheromatous calcification in his popliteal and tibia1 arteries might well lose his leg because of a calcium free obstruction in the distal superficial femoral artery. However valuable conventional roentgenography of the chest or other body areas and the many other diagnostic approaches to arteriosclerosis may be, without arteriography, they are not enough. Any patient who stands to benefit from the relief of arteriosclerotic ischemia (which includes most of those who suffer from it) needs arteriography. To belabor the point once more: only arteriography can provide the direct anatomic information needed for competent treatment planning. Modern arteriography is reliable, informative, and safer than the alternative of incomplete anatomic diagnosis. High quality studies are possible with several different techniques, most of which involve some form of selective catheterization. Whilst the angiographer’s modus operandi and the site of suspected disease will inlluence the choice of procedure, how it’s done is usually not as important as how well. The following regional survey of the radiologic morphology of arteriosclerosis is, of necessity, angiographically oriented.
Thora&
Aorta
In addition to elongation, tortuosity, and calcification, arteriosclerosis causes aneurysm, rupture, and dissection of the thoracic aorta. Although all of these can ordinarily be detected by conventional chest roentgeno’graphy, thoracic aortography is usually indicated when potentially lethal lesions are suspected. Whereas a rounded saccular aneurysm of the ascending and transverse aorta is likely to be syphilitic, its differentation from an arterio’sclerotic aneurysm may be difficult. Characteristically, the arteriosclerotic aneurysm occurs in the distal transverse or descending segment of the thoracic aorta and tends to be more angular or irregular in contour. When a localized prominence of the descending aorta undergoes sudden, painful, and continuing enlargement, when its previously sharp margin becomes locally indistinct, especially if accompanied by a surrounding corona of pulmonary density or the sudden appearance of pleural fluid on the same side, then emergency aortography is warranted, for these findings may well mean that blood is seeping through a locally thinned, weakened s’egment of aortic wall and that catastrophic aortic rupture is imminent.” In such a situation, the reactive development of a thickwalled false aneurysm may provide at least a temporary period of stability and a better chanoe for successful surgery ( Fig. 3). Aortic dissection may be due to a congenitally defective media, especially
232.
CHARLES
T.
DOTTER
Fig. 3.-Large, thick-walled, false aneurysm arising posteriorly from an atherosclerotic thoracic aorta. The outer wall of the false aneurysm is indicated hy arrows.
in young people, but it also occurs as a serious complication of aortic arteriosclerosis. Supersudden enlargement of a previously unremarkable arch and descending aorta makes its recognition possible without aortography, especially when intimal calcification is visible well within the outer border. Aortography can be expected to show gross narrowing of the compressed aortic lumen, the proximal point of dissection, and the extent of branch artery involvement. Dissection may or may not proceed to a point of distal reentry. If it does, a functioning false channel can often be visualized. Suspected aortic dissection is an indication for catheter aortography, not a contraindication. Surgery can be lifesaving and the more the surgeon knows about the problem, the better his chances of solving it. Thoracic dissection often continues down to a point of reentry in the abdominal aorta ( Fig. 4). Carotid/Vertebral
Arteries
Localized arteriosclerotic obstruction commonly affects the origins of the brachiocephalic and vertebral arteries, in which case a good arch injection will suffice. More distal lesions warrant selective catheterization. In either case, the resulting compensatory flow patterns depend upon the vessel(s) obstructed. After considerable experience in the performance of both approaches, I have become firmly convinced that carotid/vertebral arteriography should be routinely done by femoral catheterization, not by direct needle puncture in the neck. The use of suitable preshaped “head hunter” catheters gives complete
ARTERIOSCLEROSIS
233
extra- and intracranial four vessel studies with but one easily accomplished insertion done at a safe distance from the diseased arteries being studied.4 Selective catheterization permits reasonable patient mobility without fear of needle dislodgment; it is more comfortable and less frightening for the patient, and requires no general anesthetic. It’s easier to do and safer, particularly in the presence of carotid bifurcation obstruction which heightens the penalty of a traumatic direct puncture and increases the need for studying the entire artery. Carotid bifurcation obstruction due to atherosclerosis (Fig. 5) is often If it is sharply localized with relatively normal intima above and below. detected before the occurrence of complicating distal thrombosis, the results of local reconstructive surgery (endarterectomy, patch graft angioplasty) are very gratifying. Any patient with transient visual disturbances and a localized carotid bruit should have appropriate selective catheter angiography performed without undue delay. All arteries to the head should be studied.
Coronary Arteries In the decade to come, radiology will obviously play a crucial role in the diagnosis and management of coronary arteriosclerosis. Sones’ pioneering
Fig. 4.-Dissecting aneurysm in abdominal aorta. Lower end of ex-
tension from thoracic aorta. Arrow marks terminus of false lumen situated just behind the true lumen.
234
CHARLES
T.
D07TbX
demonstration of the feasibility of selective coronary catheterization constituted a major stride out of the nihilistic approach that characterized supportive therapy in coronary disease. Judkins, working in o’ur laboratory, developed the tools and technique for femoral selective coronary catheterization now in widespread use and showed the value of serial, high definition, short exposure, direct radiographs as an excellent supplement to tine coronary angiography.: In over 3000 consecutive coronary angiograms, performed at this center using preshaped coronary-seeking catheters and Renografin 76 per cent as the contrast agent, there was not a single instance of ventricular fibrillation and no occasion for arteriotomyl
Fig. 5.-Atherosclerotic carotid bifurcation stenosis. The proximal in-
ternal carotid lumen is threadlike (arrow), The external carotid is markedly narrowed.
The impressive anatomic detail afforded by direct radiographs is readily illustrated on the printed page (Figs. 6 and 7)) which is an advantage over Although we routinely perform septechniques limited to cineangiography. arate cineangiographic studies of both coronaries in the three standard projections, in practice we use tine primarily for studying left ventricular contraction, a routine component of coronary angiography. The importance of coronary angiography is attested to daily in our own angiography laboratory, where the demands for such studies have proved taxing on what were previously adequate facilities for a community of our size. The reason for this greatly increased demand is simple: the detailed anatomic studies of the coronary arteries provide a more adequate diagnosis and thereby aid in a successful attack by means of aortocoronary bypass grafting.
235
ARTERIOSCLEROSIS
Fig. B.-Severe
localized
stenosis of right coronary artery.
Abdominal Aorta, Iliac Arteries as well as above the diaphragm, man’s aorta is subject to arteriosclerotic aneurysm ( Fi,.m S), rupture, and dissection. In addition, the aortic bifurcation and common ihac arteries are prone to atheromatous obstruction with thrombotic progression, frequently to complete occlusion (Fig. 9). Secondary thrombosis tends to ascend from the bifurcation to the orifices of the renal arteries. As it does so, the intervening lumbar arteries are occluded, removing important collateral channels and adding to the severity of the pelvic and lower extremity ischemia. Celiac and mesenteric arteries often serve as collaterals in aorto-iliac occlusion, and the sudden occlusion of one of thelse visceral arteries can lead to gangrene, not of the bowel, but of a lower extremity. In the presence of aortic bifurcation occlusion, it seems reasonable to Below
236
CHARLES
T.
DOTTER
Fig. 7.-Stenosis of left anterior descending coronary artery (upper arrow). The circumflex is also completely occluded ahout an inch from its origin (lower arrow).
attribute ascending thrombotic occlusion to relative stagnation and attendant platelet deposition in the blindly terminated aortic stub. In a sense, renal blood flow seems to protect itself, for ascending thrombosis tends to stop just belo’w the renal artery orifices, not always, but frequently enough to have spared many lives. Atherothrombosis of the distal aorta, also called Leriche’s syndrome, is readily relieved by graft replacement or endarterectomy. When such surgery fails to relieve obstruction in the internal iliac arteries, gluteal claudication and It has been said that the internal iliac male impoltency may be permanent. arteries are rarely occluded, but this is not so. It does appear, however, that the isolated development of aortic or common iliac occlusion slows the progress of occlusive disease distally.
237
ARTERIOSCLEROSIS
This sparing effect of proximal disease occurs in other segments of the arterial bed and partly accounts for the clinical benefits gained from proximally directed surgery. The presence of poorly filled, small, run-off arteries. does not contraindicate such surgery even when luminal irregularity indicates that they, too, are diseased. The remarkable increase in calib’er associated with the physical removal of a proximal occlusion or gradient producing stenosis attests to the value of restoring a respectable perfusion pressure. However diseased run-off arteries may be, any patent ones will do a lot better when given the chance. This is now generally accepted with respect to aorto-iliac disease; it is not as widely accepted that it is equally true for the coronaries. Visceral Abdominal
Aortic
Branches
The celiac trunk and the superior and inferior mesenteric arteries are prone to atherostenosis, singly or in combination (Fig. 10). As long as at least one of these three, important, interconnected pathways remains open to the aorta, surprisingly effective flow adaptation takes place. A patent inferior mesenteric can, for example, supply the needs of proximally occluded but oltherwise open superior mesenteric and celiac arteries via the marginal artery and other interconnections. This being so, abdominal angina is apt to signify serious, multiple, trunk obstruction. The renal arteries are similarly subject to arteriosclerotic narrowing close to their origins (Fig. 11). Collateral flow in the presence of complete occlusion is capable of preventing renal infarction and even of sustaining a measure of renal function. Because of the pressure-regulating function of the kidneys,
Fig. S.-Atherosclerotic ahdominal aortic aneurysm also involving
the iliac arteries.
Fig. 9.-Aorto-iliac stenosis. A. The abnormality struction and diffuse disease above and below.
is limited
to the bifurcation.
B. Another
patient
with bifurcation
ob-
239
ARTERIOSCLEROSIS
Fig. lo.-Atherosclerotic lateral projection.
stenosis of celiac and superior mesenteric
arteries. Near
a relatively modest stenosis in one renal artery can give rise to serious hypertension everywhere else in the patient. Surgery is usually successful in correcting the stenosis and sometimes the hypertension, although transluminal catheter dilatation would appear (to me at least) to offer a simple, equally effective, and much safer way of doing the same thing, perhaps on an outpatient basis! however,
Femoropopliteal
Arteries
Just beyond the inguinal ligament, the common femoral artery divides into the deep and superficial femoral arteries. The latter proceeds do’wnward, then medially and posteriorly through the adductor hiatus, where it enters the popliteal fossa and changes its name accordingly. The popliteal artery passes downward posterior to the knee joint, a few centimeters below which it bifurcates into the anterior and posterior tibia1 arteries. The latter soon gives off the peroneal artery. Atherosclerosis rarely causes significant obstruction of either the common or
240
Fig.
CHARLES
Il.-Renal
artery stenosis.
T.
DOTTER
Paired right and single left renal arteries are all
stenotic. deep femoral arteries. The patient with intermittent claudication and rest pain, with or witho’ut gangrene of the toes, who has a good femoral but absent or weak popliteal pulse will usually have localized narrowing or complete occlusion of his distal superficial femoral artery in the region of the adductor hiatus (Fig. 12A). Presumably because of distal flow through deep femoralpopliteal collateral arteries, stenosis or segmental occlusion at this site tends to lead to thrombotic obliteration of the proximal blind stub of the virtually Popliteal disease is frequently also present functionless superficial femoral. and leads to further compromise in distal flour. Generalized disease can lead to the simultaneous development of separate lesions in and below the distal superficial femoral. A single localized obstruction tends to protect the distal branches against similar changes or at least slows down the process. It is a common fallacy to place undue emphasis on the effect of concomitant small artery disease. Small vessel disease may be an important factor in anyone’s gangrene, although I am not convinced that it is. I am convinced only that if there is significant proximal disease, regardless of the small arteries, removal of the proximal obstruction will result in marked improvement. A single, proximal, gradient producing obstruction or occlusion results in reduced perfusion pressure and thus lowered flow through every distal branch that has any degree of patency. Compared with those in the legs, arteries in the arms are rarely the site of Arteriosclerotic in the sense of hardened, yes; arteriosclerotic ischemia.
ARTERIOSCLEROSIS
241
242
CHARLES
T.
DOTTER
ischemia, no. The hardened, tortuous arteries in the arms of old people are the result of nonobstructing medial sclerosis. This also occurs in the leg. Perhaps there is reason for distinguishing between atherosclerosis and arteriosclerosis, but such a distinction would not find support in common usage. Transluminal
Angioplasty
in Obstructioe
Arteriosclerosis’
Much as a nail withdrawn leaves a hole which was not made by drilling or otherwise removing any wood (something like the way a footprint is pressed into, not dug out of the snow), a transluminal dilating catheter can compress and locally remodel an atheromatous core so as to enlarge the lumen (not the
Fig. 13.-Atherosclerotic occlusion involving entire left popliteal artery. A. Before and (B) immediately after transluminal recanalization from adductor hiatus to origin of the anterior and posterior tibia1 arteries. C. Despite areas of narrowing, the recanalized lumen is patent on three year follow-up arteriogram. Previously severe rest pain has not recurred. In this patient, transhuninal recanalization was done as an alternative to scheduled amputation!
ARTERIOSCLEROSIS
243
artery) without removing or detaching anything in the process. This appears to be a nearly ideal approach to the relief of atherosclerotic luminal narrowing. It is relatively easy to do, safer than surgery, and more IikeIy to work. Transluminal dilatation requires no incision, no operative exposure, no arteriotomy, no disruption of the arterial lining surface (with attendant platelet deposition), In a series of over 225 patients with no suturing, and no wound healing. arterioscIerotic ischemia of the legs treated by catheter at the University of Oregon Medical School since January 16, 1964, transluminal dilatation has had an overall success rate of better than SO per cent (Fig. 12B). It is at its best in the presence of relatively firm, established stenoses; early, soft narrowings which offer littIe resistance to dilatation arc more likely to recur. Fortunately, the latter are rare and, since they become sclerotic in the course of a few months, can be retreated successfully. Complete occlusion is understandably not as readily treated by catheter, especially when associated with secondary, soft, thrombotic occlusion developHere, transluminal ing above a site of primary atherosclerotic stenosis. recanalization (as opposed to dilatation) involves probing a neohunen through
Fig. 14.-Treatment of acutely thrombosed left external iliac artery with streptokinase. A. Visualization by transaxillary route. Sharp cutoff (arrow) marks upper
end of thrombosed external iliac artery one day following traumatic retrograde femora1 catheterization. B. After three days of continuous infusion of streptokinase, the previously pulseless leg is now normal. No apparent effect on the chronic, completely occluded, right iliac system.
244
CHARLES T. DOTTER
the occluded segment. In such a situation, it may be difficult o’r impossib’le to keep out of the periatheromatous cleavage plane, which is not a favorable route for continued patency. Transthrombic pathways lack the lining surface of the dilated stenosis and they are far more likely to reocclude within hours, weeks, or months of an initially successful procedure. Overall, we have had lasting success in about 30 per cent of such iesions; good results are more 1ikeIy to result when the occlusion is short and localized. Drawbacks of recanalization notwithstanding, it has produced some spectacular results in patients who would not or could not have reconstructive vascular surgery (Fig. In). Attempted transluminal recanalization is a far better bet than amputation and has saved a number of otherwise doomed legs. Where dilatation by catheter is feasible, i.e., in the presence of simple stenosis, it should be done in preference to surgery or watchful waiting. The risk is approximately that of arteriography; the gain is that of definitive therapy. Those planning to use the technique should make sure they understand how to go about it and should make every effort to treat patients who are most likely to benefit. This may not always be easy to arrange, since it usually involves patients who are thought to be good surgical candidates. Streptokinase
in Arterial
Occlusion
Recent experience with a new purified streptokinase (Streptase, Hoechst pharmaceutical Co.) indicates that it can dissolve fresh clots in situ (Fig. 14) and is capable of relieving chronic (several months old) arterial occlusions, particularly in the distal aorta and the common iliac arteries.G Its application to secondary, long segment, superficial, femoral thrombo’sis, followed by transluminal dilatation of the primary atherosclerotic narrowing, is currently being explored in our laboratory. REFERENCES 4. Hinck, V. C., and Dotter, C. T.: Ap1. Dotter, C. T., E’rische,L. H., Judkins, M. P., and Mueller, R.: The “nonsurgical” praisal of current techniques for cerebral treatment of ihofemoral arteriosclerotic ob- angiography. Amer. J. Roentgen. 107:626, 1969. struction. Radiology 86:871, 1966. 5. Judkins, hl. P.: Percutaneous trans2. Dotter, C. T., Niles, N. R., and Steinberg, 1.: Impending aortic rupture: Pathogenesis of x-ray signs. New Eng. J. Med. 265214, 1961. 3. F&on, W. F. M.: The Coronary Arteries. Springfield, Ill., Charles C Thomas, 1965, Chap. 7.
femoral selective coronary arteriography. Radio!. Clin. N. Amer. 6:467, 1968. 6. Martin, M., &hoop, W., and Zeitler, E.: Streptokinase in chronic arterial occlusive disease. JAMA 211:1169, 1970.
E
VEN AT THE RISK of putting some unwanted punch into the threatened population explo,sion, the conquest of arteriosclerosis amounts to medicine’s moist important unfinished business. Barring nuclear catastrophe, environmental toxification, and possibly the SDS, it is a statistical near-certainty that the subject of this chapter will sooner or later do in most of its readers! GENERAL NATURE OF ARTERIOSCLEROSIS/ATHEROSCLEROSIS
It is next to impossible to say anything noncontroversial about the basic nature of arteriosclerosis. Experts who, by virtue of their special interest and scientific experience, should know most about it, seem to be least agreed as to what it is, what causes it, how to treat it, and even what to call it. A.s to the semantics, regardless of whether you call it arteriosclerosis or atherosclerosis, a few will take issue, but nearly everyone will know what y-ou mean. With res’pect to etiology, abnormal plasma lipids, dietary habits, inherited metabolic defects, emotional states, sticky platelets, too much fibrin, too little fibrinolysis, hypertension, diabetes, the sedentary life, and smoking have all been blamed for atherogenesis. To add to the confusion (mine anyway), opinions and research on the issue appear to have suffered the consequences of po,larization and partisansship. No doubt influenced by a background in angiography, I take a pragmatic, essentially morphologic approach to atherosclerosis, sharing Fulton’s view that lipid accumulation is a result rather than a cause: o’f early intimal thickening and that progressive luminal narrowing comes about through the repeated deposition of platelets and fibrin and their subsequent conversion into the familiar atherosclerotic lesion.” While the foregoing concept of atherogenesis is certainly not universally accepted, even the Friends of Beta Lipoproteins concede the importance of thrombosis at the time of final luminal obliteration. Here the role of the coagulation mechanism is more apparent than during earlier phases of atherogenesis, perhaps because complete occlusion favors frank thrombosis and alters the atherogenic conversion process. Often, the clinical consequences of acute final occlusion lead to pathologic examination before there is time for the clot to stop looking like a clot. Whatever the basic mechanism, atherosclerotic luminal narrowing is the result of the progressive replacement of normal intima by a thickened core of inelastic collagenous material ( Fig. 1) . The core is loosely attached to the surrounding, more or less intact, media. Purposeful, if chauvinistic, vascular surgeons refer to this zone of IO~XXattachment as the “plane of endarterectomy.” Better to call it the “periatheromatous cleavage plane,” since it also can be the site of localized subintimal hemorrhage, the route of dissecting aneurysm, This uork uxs suppsrted ly C’SPHS Grant HE 03275-13. CHARLES T. DWTSH, M.D.: Professor and Chairmun, Depzrtment of Radiology, UniversiW of Oregon Medicul School; Stelln ujd Charles Guttman Lahoxtory, Portland, Ore. 97201.
229
ARTFBIOSCLEROSIS
Fig.
l.-Cross
section, atherosclerotic
popliteal
artery,
and a pathway for catheter dissection. When visualized during arteriography, it presents a typical appearance ( Fig. 2). Whereas atheromatous intimal change is usually diffuse, clinically significant obstruction often occurs at particular sites of predilection, such as the adductor hiatus, the carotid and aortic b’ifurcations, and the origins of the renal, celiac, mesenteric, and coronary arteries. The tendency for localized obstruction to develop at points of arterial origin, branching, fixation, etc., suggests that hemodynamic and other forms of mechanical trauma are contributory factors in atherogenesis. Other evidence: atherosclerosis correlates with hypertension; proximal obstruction spares the distal bed; degenerative changes commonly appear at sites of jet impact, in association with congenital and acquired aortic valvular deformities, and as late complicatioSns of vascular surgery. However speculative the connection between localized disease and mechanical factors in atherogenesis, predilective sites of obstruction are so common as to constitute clinical facts of life or death, ARTEHIOGRAPHY
Although symptoms of ischemia bring the patient to his doctor and often suggest what’s wrong, precordial pain doesn’t always mean coronary disease and intermittent claudication doesn’t necessarily indicate the site of the responsible arterial obstruction. Physical examination is often of considerable diagnostic aid, particularly palpation and auscultation of accessible arteries; unfortunately, many important arterial narrcwings can’t be detected in this manner. Segmental blood pressure determinations may show a gradient in the
Fig. 2.-Periatheromatous The lumen of the artery nnclrl,,‘3 nr,n ,P”,A lotor
Pm;nehm.mnotn,,c
/a,,l-rintimal~
rnntrart
cleavage plane, left iliac artery. A. is opacified. B. The lumen remains
material parallels the lateral aspect of the lumen (arrow). C. Two seconds later, the lumen is empty. Contrast material persists in the P~P:IVRU~nl~ne hilt will shol-tlv he washed awav.
2 g
:
ARTERIOSCLEROSIS
231
legs and thus spot a level of obstruction. Ultrasonic and plethysmographic studies are similarly useful indicators of arterial obstruction, if not centrally, at least in the peripheral arteries, While the EKG can be counted upon to reveal myocardial damage or ischemia consequent to impaired coronary flow, it is o’f little value in determining the feasibility of corrective surgery. The roentgen identification and characterization of calcium in arteries aid by revealing probable sites of atheromatous disease, outlining otherwise hidden aneurysms, suggesting the diagnosis of syphilitic aortitis, and disclosing benign medial sclerosis ( Monckeberg’s) , On the other hand, typical atheromatous calcification can be present in the absence of significant hm~inal narrowing, and vice versa. A patient with localized atheromatous calcification in his popliteal and tibia1 arteries might well lose his leg because of a calcium free obstruction in the distal superficial femoral artery. However valuable conventional roentgenography of the chest or other body areas and the many other diagnostic approaches to arteriosclerosis may be, without arteriography, they are not enough. Any patient who stands to benefit from the relief of arteriosclerotic ischemia (which includes most of those who suffer from it) needs arteriography. To belabor the point once more: only arteriography can provide the direct anatomic information needed for competent treatment planning. Modern arteriography is reliable, informative, and safer than the alternative of incomplete anatomic diagnosis. High quality studies are possible with several different techniques, most of which involve some form of selective catheterization. Whilst the angiographer’s modus operandi and the site of suspected disease will inlluence the choice of procedure, how it’s done is usually not as important as how well. The following regional survey of the radiologic morphology of arteriosclerosis is, of necessity, angiographically oriented.
Thora&
Aorta
In addition to elongation, tortuosity, and calcification, arteriosclerosis causes aneurysm, rupture, and dissection of the thoracic aorta. Although all of these can ordinarily be detected by conventional chest roentgeno’graphy, thoracic aortography is usually indicated when potentially lethal lesions are suspected. Whereas a rounded saccular aneurysm of the ascending and transverse aorta is likely to be syphilitic, its differentation from an arterio’sclerotic aneurysm may be difficult. Characteristically, the arteriosclerotic aneurysm occurs in the distal transverse or descending segment of the thoracic aorta and tends to be more angular or irregular in contour. When a localized prominence of the descending aorta undergoes sudden, painful, and continuing enlargement, when its previously sharp margin becomes locally indistinct, especially if accompanied by a surrounding corona of pulmonary density or the sudden appearance of pleural fluid on the same side, then emergency aortography is warranted, for these findings may well mean that blood is seeping through a locally thinned, weakened s’egment of aortic wall and that catastrophic aortic rupture is imminent.” In such a situation, the reactive development of a thickwalled false aneurysm may provide at least a temporary period of stability and a better chanoe for successful surgery ( Fig. 3). Aortic dissection may be due to a congenitally defective media, especially
232.
CHARLES
T.
DOTTER
Fig. 3.-Large, thick-walled, false aneurysm arising posteriorly from an atherosclerotic thoracic aorta. The outer wall of the false aneurysm is indicated hy arrows.
in young people, but it also occurs as a serious complication of aortic arteriosclerosis. Supersudden enlargement of a previously unremarkable arch and descending aorta makes its recognition possible without aortography, especially when intimal calcification is visible well within the outer border. Aortography can be expected to show gross narrowing of the compressed aortic lumen, the proximal point of dissection, and the extent of branch artery involvement. Dissection may or may not proceed to a point of distal reentry. If it does, a functioning false channel can often be visualized. Suspected aortic dissection is an indication for catheter aortography, not a contraindication. Surgery can be lifesaving and the more the surgeon knows about the problem, the better his chances of solving it. Thoracic dissection often continues down to a point of reentry in the abdominal aorta ( Fig. 4). Carotid/Vertebral
Arteries
Localized arteriosclerotic obstruction commonly affects the origins of the brachiocephalic and vertebral arteries, in which case a good arch injection will suffice. More distal lesions warrant selective catheterization. In either case, the resulting compensatory flow patterns depend upon the vessel(s) obstructed. After considerable experience in the performance of both approaches, I have become firmly convinced that carotid/vertebral arteriography should be routinely done by femoral catheterization, not by direct needle puncture in the neck. The use of suitable preshaped “head hunter” catheters gives complete
ARTERIOSCLEROSIS
233
extra- and intracranial four vessel studies with but one easily accomplished insertion done at a safe distance from the diseased arteries being studied.4 Selective catheterization permits reasonable patient mobility without fear of needle dislodgment; it is more comfortable and less frightening for the patient, and requires no general anesthetic. It’s easier to do and safer, particularly in the presence of carotid bifurcation obstruction which heightens the penalty of a traumatic direct puncture and increases the need for studying the entire artery. Carotid bifurcation obstruction due to atherosclerosis (Fig. 5) is often If it is sharply localized with relatively normal intima above and below. detected before the occurrence of complicating distal thrombosis, the results of local reconstructive surgery (endarterectomy, patch graft angioplasty) are very gratifying. Any patient with transient visual disturbances and a localized carotid bruit should have appropriate selective catheter angiography performed without undue delay. All arteries to the head should be studied.
Coronary Arteries In the decade to come, radiology will obviously play a crucial role in the diagnosis and management of coronary arteriosclerosis. Sones’ pioneering
Fig. 4.-Dissecting aneurysm in abdominal aorta. Lower end of ex-
tension from thoracic aorta. Arrow marks terminus of false lumen situated just behind the true lumen.
234
CHARLES
T.
D07TbX
demonstration of the feasibility of selective coronary catheterization constituted a major stride out of the nihilistic approach that characterized supportive therapy in coronary disease. Judkins, working in o’ur laboratory, developed the tools and technique for femoral selective coronary catheterization now in widespread use and showed the value of serial, high definition, short exposure, direct radiographs as an excellent supplement to tine coronary angiography.: In over 3000 consecutive coronary angiograms, performed at this center using preshaped coronary-seeking catheters and Renografin 76 per cent as the contrast agent, there was not a single instance of ventricular fibrillation and no occasion for arteriotomyl
Fig. 5.-Atherosclerotic carotid bifurcation stenosis. The proximal in-
ternal carotid lumen is threadlike (arrow), The external carotid is markedly narrowed.
The impressive anatomic detail afforded by direct radiographs is readily illustrated on the printed page (Figs. 6 and 7)) which is an advantage over Although we routinely perform septechniques limited to cineangiography. arate cineangiographic studies of both coronaries in the three standard projections, in practice we use tine primarily for studying left ventricular contraction, a routine component of coronary angiography. The importance of coronary angiography is attested to daily in our own angiography laboratory, where the demands for such studies have proved taxing on what were previously adequate facilities for a community of our size. The reason for this greatly increased demand is simple: the detailed anatomic studies of the coronary arteries provide a more adequate diagnosis and thereby aid in a successful attack by means of aortocoronary bypass grafting.
235
ARTERIOSCLEROSIS
Fig. B.-Severe
localized
stenosis of right coronary artery.
Abdominal Aorta, Iliac Arteries as well as above the diaphragm, man’s aorta is subject to arteriosclerotic aneurysm ( Fi,.m S), rupture, and dissection. In addition, the aortic bifurcation and common ihac arteries are prone to atheromatous obstruction with thrombotic progression, frequently to complete occlusion (Fig. 9). Secondary thrombosis tends to ascend from the bifurcation to the orifices of the renal arteries. As it does so, the intervening lumbar arteries are occluded, removing important collateral channels and adding to the severity of the pelvic and lower extremity ischemia. Celiac and mesenteric arteries often serve as collaterals in aorto-iliac occlusion, and the sudden occlusion of one of thelse visceral arteries can lead to gangrene, not of the bowel, but of a lower extremity. In the presence of aortic bifurcation occlusion, it seems reasonable to Below
236
CHARLES
T.
DOTTER
Fig. 7.-Stenosis of left anterior descending coronary artery (upper arrow). The circumflex is also completely occluded ahout an inch from its origin (lower arrow).
attribute ascending thrombotic occlusion to relative stagnation and attendant platelet deposition in the blindly terminated aortic stub. In a sense, renal blood flow seems to protect itself, for ascending thrombosis tends to stop just belo’w the renal artery orifices, not always, but frequently enough to have spared many lives. Atherothrombosis of the distal aorta, also called Leriche’s syndrome, is readily relieved by graft replacement or endarterectomy. When such surgery fails to relieve obstruction in the internal iliac arteries, gluteal claudication and It has been said that the internal iliac male impoltency may be permanent. arteries are rarely occluded, but this is not so. It does appear, however, that the isolated development of aortic or common iliac occlusion slows the progress of occlusive disease distally.
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ARTERIOSCLEROSIS
This sparing effect of proximal disease occurs in other segments of the arterial bed and partly accounts for the clinical benefits gained from proximally directed surgery. The presence of poorly filled, small, run-off arteries. does not contraindicate such surgery even when luminal irregularity indicates that they, too, are diseased. The remarkable increase in calib’er associated with the physical removal of a proximal occlusion or gradient producing stenosis attests to the value of restoring a respectable perfusion pressure. However diseased run-off arteries may be, any patent ones will do a lot better when given the chance. This is now generally accepted with respect to aorto-iliac disease; it is not as widely accepted that it is equally true for the coronaries. Visceral Abdominal
Aortic
Branches
The celiac trunk and the superior and inferior mesenteric arteries are prone to atherostenosis, singly or in combination (Fig. 10). As long as at least one of these three, important, interconnected pathways remains open to the aorta, surprisingly effective flow adaptation takes place. A patent inferior mesenteric can, for example, supply the needs of proximally occluded but oltherwise open superior mesenteric and celiac arteries via the marginal artery and other interconnections. This being so, abdominal angina is apt to signify serious, multiple, trunk obstruction. The renal arteries are similarly subject to arteriosclerotic narrowing close to their origins (Fig. 11). Collateral flow in the presence of complete occlusion is capable of preventing renal infarction and even of sustaining a measure of renal function. Because of the pressure-regulating function of the kidneys,
Fig. S.-Atherosclerotic ahdominal aortic aneurysm also involving
the iliac arteries.
Fig. 9.-Aorto-iliac stenosis. A. The abnormality struction and diffuse disease above and below.
is limited
to the bifurcation.
B. Another
patient
with bifurcation
ob-
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ARTERIOSCLEROSIS
Fig. lo.-Atherosclerotic lateral projection.
stenosis of celiac and superior mesenteric
arteries. Near
a relatively modest stenosis in one renal artery can give rise to serious hypertension everywhere else in the patient. Surgery is usually successful in correcting the stenosis and sometimes the hypertension, although transluminal catheter dilatation would appear (to me at least) to offer a simple, equally effective, and much safer way of doing the same thing, perhaps on an outpatient basis! however,
Femoropopliteal
Arteries
Just beyond the inguinal ligament, the common femoral artery divides into the deep and superficial femoral arteries. The latter proceeds do’wnward, then medially and posteriorly through the adductor hiatus, where it enters the popliteal fossa and changes its name accordingly. The popliteal artery passes downward posterior to the knee joint, a few centimeters below which it bifurcates into the anterior and posterior tibia1 arteries. The latter soon gives off the peroneal artery. Atherosclerosis rarely causes significant obstruction of either the common or
240
Fig.
CHARLES
Il.-Renal
artery stenosis.
T.
DOTTER
Paired right and single left renal arteries are all
stenotic. deep femoral arteries. The patient with intermittent claudication and rest pain, with or witho’ut gangrene of the toes, who has a good femoral but absent or weak popliteal pulse will usually have localized narrowing or complete occlusion of his distal superficial femoral artery in the region of the adductor hiatus (Fig. 12A). Presumably because of distal flow through deep femoralpopliteal collateral arteries, stenosis or segmental occlusion at this site tends to lead to thrombotic obliteration of the proximal blind stub of the virtually Popliteal disease is frequently also present functionless superficial femoral. and leads to further compromise in distal flour. Generalized disease can lead to the simultaneous development of separate lesions in and below the distal superficial femoral. A single localized obstruction tends to protect the distal branches against similar changes or at least slows down the process. It is a common fallacy to place undue emphasis on the effect of concomitant small artery disease. Small vessel disease may be an important factor in anyone’s gangrene, although I am not convinced that it is. I am convinced only that if there is significant proximal disease, regardless of the small arteries, removal of the proximal obstruction will result in marked improvement. A single, proximal, gradient producing obstruction or occlusion results in reduced perfusion pressure and thus lowered flow through every distal branch that has any degree of patency. Compared with those in the legs, arteries in the arms are rarely the site of Arteriosclerotic in the sense of hardened, yes; arteriosclerotic ischemia.
ARTERIOSCLEROSIS
241
242
CHARLES
T.
DOTTER
ischemia, no. The hardened, tortuous arteries in the arms of old people are the result of nonobstructing medial sclerosis. This also occurs in the leg. Perhaps there is reason for distinguishing between atherosclerosis and arteriosclerosis, but such a distinction would not find support in common usage. Transluminal
Angioplasty
in Obstructioe
Arteriosclerosis’
Much as a nail withdrawn leaves a hole which was not made by drilling or otherwise removing any wood (something like the way a footprint is pressed into, not dug out of the snow), a transluminal dilating catheter can compress and locally remodel an atheromatous core so as to enlarge the lumen (not the
Fig. 13.-Atherosclerotic occlusion involving entire left popliteal artery. A. Before and (B) immediately after transluminal recanalization from adductor hiatus to origin of the anterior and posterior tibia1 arteries. C. Despite areas of narrowing, the recanalized lumen is patent on three year follow-up arteriogram. Previously severe rest pain has not recurred. In this patient, transhuninal recanalization was done as an alternative to scheduled amputation!
ARTERIOSCLEROSIS
243
artery) without removing or detaching anything in the process. This appears to be a nearly ideal approach to the relief of atherosclerotic luminal narrowing. It is relatively easy to do, safer than surgery, and more IikeIy to work. Transluminal dilatation requires no incision, no operative exposure, no arteriotomy, no disruption of the arterial lining surface (with attendant platelet deposition), In a series of over 225 patients with no suturing, and no wound healing. arterioscIerotic ischemia of the legs treated by catheter at the University of Oregon Medical School since January 16, 1964, transluminal dilatation has had an overall success rate of better than SO per cent (Fig. 12B). It is at its best in the presence of relatively firm, established stenoses; early, soft narrowings which offer littIe resistance to dilatation arc more likely to recur. Fortunately, the latter are rare and, since they become sclerotic in the course of a few months, can be retreated successfully. Complete occlusion is understandably not as readily treated by catheter, especially when associated with secondary, soft, thrombotic occlusion developHere, transluminal ing above a site of primary atherosclerotic stenosis. recanalization (as opposed to dilatation) involves probing a neohunen through
Fig. 14.-Treatment of acutely thrombosed left external iliac artery with streptokinase. A. Visualization by transaxillary route. Sharp cutoff (arrow) marks upper
end of thrombosed external iliac artery one day following traumatic retrograde femora1 catheterization. B. After three days of continuous infusion of streptokinase, the previously pulseless leg is now normal. No apparent effect on the chronic, completely occluded, right iliac system.
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CHARLES T. DOTTER
the occluded segment. In such a situation, it may be difficult o’r impossib’le to keep out of the periatheromatous cleavage plane, which is not a favorable route for continued patency. Transthrombic pathways lack the lining surface of the dilated stenosis and they are far more likely to reocclude within hours, weeks, or months of an initially successful procedure. Overall, we have had lasting success in about 30 per cent of such iesions; good results are more 1ikeIy to result when the occlusion is short and localized. Drawbacks of recanalization notwithstanding, it has produced some spectacular results in patients who would not or could not have reconstructive vascular surgery (Fig. In). Attempted transluminal recanalization is a far better bet than amputation and has saved a number of otherwise doomed legs. Where dilatation by catheter is feasible, i.e., in the presence of simple stenosis, it should be done in preference to surgery or watchful waiting. The risk is approximately that of arteriography; the gain is that of definitive therapy. Those planning to use the technique should make sure they understand how to go about it and should make every effort to treat patients who are most likely to benefit. This may not always be easy to arrange, since it usually involves patients who are thought to be good surgical candidates. Streptokinase
in Arterial
Occlusion
Recent experience with a new purified streptokinase (Streptase, Hoechst pharmaceutical Co.) indicates that it can dissolve fresh clots in situ (Fig. 14) and is capable of relieving chronic (several months old) arterial occlusions, particularly in the distal aorta and the common iliac arteries.G Its application to secondary, long segment, superficial, femoral thrombo’sis, followed by transluminal dilatation of the primary atherosclerotic narrowing, is currently being explored in our laboratory. REFERENCES 4. Hinck, V. C., and Dotter, C. T.: Ap1. Dotter, C. T., E’rische,L. H., Judkins, M. P., and Mueller, R.: The “nonsurgical” praisal of current techniques for cerebral treatment of ihofemoral arteriosclerotic ob- angiography. Amer. J. Roentgen. 107:626, 1969. struction. Radiology 86:871, 1966. 5. Judkins, hl. P.: Percutaneous trans2. Dotter, C. T., Niles, N. R., and Steinberg, 1.: Impending aortic rupture: Pathogenesis of x-ray signs. New Eng. J. Med. 265214, 1961. 3. F&on, W. F. M.: The Coronary Arteries. Springfield, Ill., Charles C Thomas, 1965, Chap. 7.
femoral selective coronary arteriography. Radio!. Clin. N. Amer. 6:467, 1968. 6. Martin, M., &hoop, W., and Zeitler, E.: Streptokinase in chronic arterial occlusive disease. JAMA 211:1169, 1970.