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Indications for Coronary Arteriography
Indications for Coronary Arteriography BEN D. McCALLISTER, M.D.
Nearly two centuries have passed since Heberden's original description of angina pectoris; yet only within the last decade have methods been available to correlate clinical information with anatomic lesions of the coronary circulation in a living patient. Coronary arteriography, which has been largely responsible for our increased understanding of coronary-artery disease, is now an integral and essential part of the diagnostic evaluation of selected patients with heart disease in most cardiac-catheterization laboratories. The procedure can be performed consistently and with very little risk by appropriately trained personnel 15, 27 Coronary arteriography affords the clinician a method for defining the severity and degree of coronary-artery disease and selecting candidates for coronary-artery surgery. In addition, it is a means for determining the cause of diagnostic problems of chest pain as well as some types of myocardial disease. Coronary arteriography may be helpful also in the evaluation of patients whose coronary-artery disease is associated with other types of heart disease. In cases of valvular heart disease or ventricular aneurysm, the prognosis and surgical risk may be related to the extent of coronary-artery disease, which thus may be important in the selection of patients for surgery. Moreover, the clinical investigator has added new knowledge of the pathophysiology of coronary-artery disease by correlating findings at coronary arteriography with left-ventricular hemodynamics, electrocardiographic findings, and metabolic studies. The active interest in selecting patients for coronary-artery surgery has also afforded the epidemiologist a unique opportunity to follow the natural history of lesions in patients (usually those thought to be unsuitable for surgery) on medical regimens, such as exercise programs or anti-hyperlipidemic therapy.
Medical Clinics of North America- Vol. 54, No. 4, July, 1970
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TECHNIQUE Cine coronary arteriography has been the method of choice in many laboratories because of its dynamic nature ,27 although techniques utilizing high-resolution serial radiography have depicted remarkable anatomic detail. 15 The method of Sones and Shirey, in which a woven catheter is introduced via a brachial-artery incision selectively into each coronary ostium, has been replaced in many laboratories by percutaneous transfemoral selective coronary arteriography as described by Judkins. 15 Either method is satisfactory and reliable in the hands of an appropriately trained cardiologist; in the author's opinion the transfemoral method is more readily learned by those inexperienced in usual cardiac catheterization techniques, but is also more readily subject to serious complications. It is clear that either technique is safest in the hands of those most experienced with it. Multiple oblique projections are necessary in order to delineate clearly the three dimensions of arteriographic lesions. A number of manufacturers provide excellent equipment for coronary arteriography. Servicing facilities should be of prime importance in the final choice for each laboratory. Adequate pictures have been recorded with 35-mm and with over-framed 16-mm cine techniques. The latter allow more room for technical error, the former can provide larger images. Nearperfect techniques in photography, roentgenology, and film development are required for producing the information necessary for clinical decisions. The moderately obese patient should not be studied by this means, as satisfactory films will rarely be obtained. Strict attention to detail is essential: (1) arterial pressures should be monitored from the tip of the catheter, (2) the electrocardiogram should be monitored continuously, (3) the catheter system must be flushed repeatedly to prevent formation of small fibrin clots, and (4) the catheter positioning must be meticulous in order to avoid obstruction of the coronary ostium or dissection of a coronary artery during injection. After each injection, abnormalities in the ST and T waves occur, as well as a drop in arterial pressure. 3 These should return to base-line status before further injections are performed. Methylglucamine diatrizoate (Renografin-76) has been reported15 to be associated with fewer serious ventricular dysrhythmias than diatrizoate sodium (Hypaque-M, 90%), and is favored by the author. It is essential that the coronary arteriographic study be under the direction of a physician familiar with cardiovascular hemodynamics and not be considered a radiologic procedure separated from the diagnostic cardiac laboratory. Many cases require hemodynamic data in addition to coronary arteriography for determining the presence or absence of valvular or subvalvular aortic stenosis, mitral-valve disease, or myocardial disease. Accurate measurements of left-ventricular function during rest and exercise may be essential in some cases (as illustrated by cases 2 and 3, below). Preferably, hemodynamic measurements should be made before or at least 30 minutes after the injection of con-
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trast media. Elevations of left-ventricular end-diastolic pressure above the base-line figure have been seen to persist for 15 to 20 minutes after coronary arteriography and left-ventricular angiography.
COMPLICATIONS Despite the serious hazards of coronary arteriography and the severity of the diseases involved, there have been remarkably few complications in most laboratories. Strict attention to details is important in the prevention of serious events such as ventricular fibrillation, ventricular tachycardia, or marked sinus bradycardia; and availability of resuscitative and defibrillating equipment makes possible the immediate control of these occasional arrhythmias. In the author's experience, atrial pacing has not been necessary if careful attention was given to catheter-tip monitoring, prompt withdrawal of a damped catheter to allow immediate washout of contrast material, and reduction of the amount of contrast material to the minimal amount required for adequate visualization of each coronary artery in individual patients. Using methylglucamine diatrizoate (Renografin-76), Judkins 15 did not encounter an arrhythmia other than the usual transient bradycardia with more than 7,000 coronary contrast injections. In the author's experience with the same contrast medium, ventricular fibrillation or tachycardia has occurred in approximately 1 % of patients. Death and myocardial infarction have rarely been related to coronary arteriography. The author has observed one patient with severe angina decubitus who developed a myocardial infarction 16 hours after the study and subsequently died. A second patient, whose angina was worsening, developed infarction after a period of hypotension that followed an injection into the left coronary artery; and he also died subsequently. A third patient experienced a 30-minute period of chest pain during coronary arteriography; and on the next day a slight rise in the serum glutamic transaminase concentration and inverted T waves in tracings from V5 and V6 were noted. It was thought that this patient had a subendocardial infarction, since no elevation of SGOT or electrocardiographic changes had been observed 24 hours after coronary arteriography in an initial series of 100 patients so studied by the author. It seems inadvisable to perform coronary arteriography when angina pectoris has worsened recently or when myocardial infarction has occurred within 4 to 6 months, except in selected cases. Recent success with direct coronary-artery surgery may lead to a change in this conservative approach in the future. Local thrombotic complications may develop at the site of the brachial arteriotomy, but significant compromise of the arm circulation is rare. Use of a Fogarty catheter to remove clots, both distally and proximally, prior to closure of the arteriotomy incision has greatly reduced the incidence of decreased radial pulse in the author's experience. Early consultation and exploration of an artery by a vascular surgeon is advisable if occlusion occurs with associated evidence of circulatory
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impairment. With transfemoral technique, thrombotic complications sometimes appear in the femoral artery and are usually related to intimal injury.15 From 1500 examinations Judkins 16 reported 0.6% had complications at the femoral puncture site, of which 0.4% were minor and 0.2% major (requiring ileofemoral surgery).
CLARIFICATION, EVALUATION, DIAGNOSIS Diagnostic Chest-Pain Problems SIGNIFICANCE OF A NORMAL CORONARY ARTERIOGRAM. Heretofore the clinical history and the electrocardiographic tracings made at rest and during exercise have been the primary means of detecting coronaryartery disease. However, some patients with severe coronary-artery disease may be normal electrocardiographically both at rest and during exercise;7,2o and in other cases the nature of the chest pain may be uncertain. Indeed, a number of patients with chest pain receive conflicting opinions from different physicians concerning its cause, and the cardiologist may be unable to make a secure diagnosis. The evidence from coronary arteriography, if normal, can exclude atheromatous disease of the major branches of the coronary arteries, which is the pathologic finding usually associated with angina pectoris. Coronary arteriography may be of great help in reassuring the cardiac neurotic and his physician that the chest pains are benign. CASE 1. A 38-year-old mechanic first seen at the Mayo Clinic in January 1967 had a family history of heart disease. A brother had died at age 48 of a heart attack and the patient's mother and father had developed angina at ages 50 and 65, respectively. For 2 years the patient had noted substernal and precordial chest pain with moderate exertion. A dull ache in the left side of the chest occurred sometimes with excitement and sometimes spontaneously, and its severity was increasing. At first the patient had noted the pain after a hard day's work, when eating or postprandially. A number of episodes had lasted 10 minutes and had been very severe. He had taken erythrityl tetranitrate (Cardilate), dipyridamole (Persantin), and chlordiazepoxide (Librium). The initial clinical impression was that the patient had ischemic heart disease with angina pectoris. During hospitalization for 10 days there was no change in his normal electrocardiographic pattern. Anticoagulants were prescribed. The history was reviewed on a number of occasions and it was thought that the patient may well have had angina pectoris in the past; but at the time of hospitalization he did not clearly describe typical exercise-induced pain. During and after treadmill exercise for 9 minutes on a 10-degree incline at 3 miles per hour, the electrocardiographic pattern was normal. The patient became hostile on occasions because "nothing was done" for his pain, and he continued to be obsessed with the idea that he would drop dead like his brother. A diagnosis of angina pectoris could not be made with any degree of confidence. Gastric and esophageal roentgenologic findings and tracings of esophageal motility were normal. Left ventriculography, exercise left-ventricular hemodynamic study, and coronary arteriography gave normal results. The patient subsequently returned to his work as a mechanic and, with strong reassurance from his physician, has achieved excellent rehabilitation.
Available data indicate that luminal narrowing of 20 to 25% may be undetected by coronary arteriography and that more severe narrowing
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may be difficult to detect if it is circumferential or cylindrica1. 5 , 11 Generally, the estimate of narrowing observed arteriographically may be 20 to 25% less than what is demonstrated post mortem. However, pathologic studies have shown that significant arteriographic findings are uncommon in asymptomatic individuals less than 45 to 50 years of age. 1 When symptoms of ischemic heart disease are present, the pathologic changes are severe and multiple, and mostly involve proximal vessels of calibers readily visualized by coronary arteriography.18 Proudfit and associates reported that they had not found symptoms of typical angina pectoris in patients whose luminal narrowing was less than 50%. Angina pectoris is known to occur with nonarteriosclerotic heart diseases. In patients whose coronary arteries were normal, angina has accompanied valvular heart disease, myocardial disease (particularly obstructive cardiomyopathy), and various forms of pulmonary hypertension. 8 It is important that these diseases be excluded clinically or by cardiac catheterization. Only rarely have normal coronary arteriographic findings been obtained from patients with a proved history of a myocardial infarction, and the explanation for these exceptional cases is not clear. They could represent a twig occlusion in the absence of significant disease. Other cases may be results of embolic infarction from valvular lesions or prostheses. 6 Therefore a normal coronary arteriogram is strong evidence against ischemic heart disease in the patient under 50. Conversely, coronary-artery lesions are seen in a large segment of the population beyond 60 years of age, and it is hazardous to attribute complaints of atypical chest pain to ischemic heart disease in older patients, particularly those with minor lesions. Eliot and Bratt have described a group of women with symptoms of angina pectoris but normal coronary arteriograms who had abnormal oxygen-hemoglobin dissociation curves. As yet these observations remain unconfirmed by other investigators. Kemp and associates 17 also have reported a group of patients with typical angina pectoris and normal coronary arteriograms. Abnormality of the electrocardiographic tracing during exercise and an abnormality in lactate metabolism led the investigators to speculate that the angina in these patients may be related to a microangiopathy not detectable by coronary arteriography. Shirey has performed transthoracic myocardial biopsy on patients with normal coronary arteriograms and has concluded that coronary arteriography is a dependable technique for detection of coronary atherosclerosis. Disease of small myocardial vessels may occur in association with certain muscular dystrophies and collagen diseases, but the presence of these systemic disorders is usually apparent clinically from other evidence. Although the paradox of a normal coronary arteriogram in a case of angina pectoris is often explained by cardiac neurosis, a few such cases remain without explanation. At the Mayo Clinic, of 54 patients studied primarily because of diagnostic chest pain, 44 had normal coronary arteriograms, 8 had arteriographic evidence of severe coronary-artery disease, and 2 had evidence of myocardial disease in their ventriculograms and exercise left-ventricular hemodynamic values. The 44 pa-
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BEN D. MCCALLISTER
tients with normal coronary arteriograms also had normal left ventriculograms and normal exercise hemodynamics. 22 ,25 It is the author's opinion that if the coronary arteriogram, the left ventriculogram, and the left-ventricular exercise hemodynamics are normal, the patient can be assured that he does not have significant coronary-artery or myocardial disease. The patient can be further assured that his symptoms are benign and not related to the type of vascular disease (atherosclerosis) ordinarily associated with symptoms of myocardial ischemia. ELECTROCARDIOGRAPHIC ABNORMALITIES. Certain patients have unexplained electrocardiographic abnormalities that may reduce their opportunity to obtain insurance, to engage in certain professions, and to live a life free of concern about serious occult cardiac disease. One of the 54 patients mentioned above, who had an intermittent rate-dependent left bundle-branch block, was thought by the clinicians responsible for her to have coronary-artery disease; but coronary arteriography revealed no evidence of it, and the patient and her referring physician were reassured in this regard. CASE 2. A 41-year-old airline pilot first seen at the Mayo Clinic in June 1969 described an episode of substernal distress radiating to the chest and arms which had occurred in 1966 while he was flying. The discomfort was associated with difficulty in breathing and had continued intermittently for 20 minutes. These symptoms had caused him to land his aircraft before finishing the planned flight. An electrocardiogram taken subsequently had been interpreted as showing evidence of an old myocardial infarction. At this institution the physical findings were entirely normal. There were no cardiac murmurs at rest or after inhalation of amyl nitrite or on performance of the Valsalva maneuver. The electrocardiogram (Fig. 1) showed a depolarization pattern which suggested septal hypertrophy or perhaps a conduction aberration involving the posterior inferior ramification of the left bundle branch. The electrocardiographic tracings dating back to 1962 were identical to those made in 1966 and 1969. Because the patient was grounded by the Federal Aviation Administration, he requested a complete cardiac evaluation; and cardiac catheterization, including coronary arteriography, was performed in July 1969. The results of the catheterization study (Table 1) were somewhat surprising. There was no gradient across the left-ventricular outflow tract at rest or during exercise. The left-ventricular cineangiogram showed left-ventricular and probable septal hypertrophy, and it was thought that the deep Q's in leads 2 and 3, aVf, and V5 and V6 most likely reflected septal hypertrophy. (Worthy of note is the fact that electrocardiographic examination of the patient's mother in June 1969 produced an identical pattern of depolarization.) The final diagnosis was myocardiopathy, hyperdynamic type, without obstruction.
Table 1.
Hemodynamics at Rest and During Exercise (Case 2)
Left-ventricular pressure, mm Hg Left-ventricular dp/dt Cardiac index (L/min/m2 ) Stroke-volume index (mllm2 )
3
3
MIN HARD
AT REST, ON BICYCLE ERGOMETER
MIN MILD EXERCISE, 100 KG-M/MIN
EXERCISE, 300 KG-M/MIN
133/8-24 3373 3.3 46
142/12-28 3234 3.8 43
157/9-32 3650 4.2 42
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Figure 1 (case 2). Electrocardiogram (50 mm/sec) and vectorcardiogram. Note deep Q's in leads 11, Ill, aVf, and Vi) andVfj. Initial forces are anterior, to the right and upward.
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In the future the expert consultant in insurance, industrial, and aviation medicine will likely be faced with a number of challenging cases in which the resting and exercise electrocardiograms show equivocal changes, yet physiologic and coronary arteriographic data are normal. It is hoped that the patients without significant evidence of heart disease will be managed accordingly.
Ill-Defined Heart Disease Patients who present with various combinations of atypical chest pain and abnormalities among the physical, roentgenologic, and electrocardiographic findings may puzzle the clinician as to the cause of the suspected heart disease. Physiologic data, in addition to radiologic, are essential in the evaluation of these patients with ill-defined heart disease and of those considered to have clinical variants of ischemic heart disease, as is illustrated by the following two cases. CASE 3. A 59-year-old woman seen at the Mayo Clinic in August 1969 had had two episodes of chest pain diagnosed as myocardial infarction - one in 1954 and one in 1962. For 2 years the patient had experienced moderate angina pectoris with exertion and occasionally at rest. She also reported having had vague and atypical syncopal episodes over 10 years, mild pedal edema, and occasional nocturnal coughing and dyspnea. The patient was taking many cardiac medicaments. There was a family history of diabetes mellitus. One brother had had coronaryartery surgery for severe ischemic heart disease. The patient also had a history of poorly controlled hypertension and had diabetes mellitus requiring insulin therapy. The serum cholesterol measured 454 mg/100 ml and the serum triglycerides 287. Although the chest roentgenogram showed the heart as not enlarged, the electrocardiogram indicated left-ventricular hypertrophy, but without evidence of previous myocardial infarction. Physical examination revealed blood pressure of 235/110 initially and 192/102 later. The carotid upstroke was rapid and bifid. There was a grade 1/6 short midsystolic left-sternal-border murmur. After the Valsalva maneuver the murmur increased to grade 2+/6, and after administration of amyl nitrite it increased to grade 3/6 with a higher pitch. Because of the hypertension, diabetes mellitus, and family history, coronaryartery disease was strongly suspected; but the possibility of obstructive cardiomyopathy was suggested by the physical findings. The carotid tracing showed a tidal wave suggested of obstructive cardiomyopathy. Coronary arteriography and left-heart catheterization were done (Table 2). The coronary arteriogram was normal. The left ventriculogram showed marked
Table 2.
Hemodynamic Data Under Control Conditions and After Administration of Isoproterenol (Case 3)
Femoral-artery pressure, mm Hg Left-ventricular pressure, mm Hg Cardiac output, L/min
UNDER CONTROL CONDITIONS
AFTER INFUSION OF ISOPROTERENOL (0.04 IJ-G/KG/MIN)
215/68 198/6-15 4.8
192/68 31/-2 to 15 5.5
INDICATIONS FOR CORONARY ARTERIOGRAPHY
Figure 2 (case 4). within normal limits.
987
Normal cardiothoracic ratio: left-ventricular contour is generous, but
concentric hypertrophy of the left ventricle with narrowing of the left-ventricular outflow tract during systole, characteristic of idiopathic hypertrophic subaortic stenosis. Propranolol therapy brought a decrease in the intensity of the murmur and improvement in the clinical symptoms.
Noteworthy is the fact that five patients who had a diagnosis of coronary-artery disease and were referred to the Mayo Clinic for coronary arteriography have been demonstrated to have idiopathic hypertrophic subaortic stenosis. At the time of the hemodynamic study one of these had both idiopathic hypertrophic subaortic stenosis and significant coronary-artery disease. CASE 4. A 46-year-old man who came to the Mayo Clinic in September 1967 had had episodes of chest pain at ages 37 and 42 which had been diagnosed as myocardial infarctions. Thereafter, he had been free of symptoms until April 1967, when he had had three episodes of acute dyspnea, each of which occurred while he was playing golf. At the time of admission the roentgenographic silhouette of the heart was normal (Fig. 2). The electrocardiogram showed evidence of old anteroseptal and possible inferior scars (Fig. 3). There was a loud third heart sound but no definite murmur. In October coronary-arteriography revealed severe stenoses of the left anterior descending and left circumflex coronary arteries and complete occlusion of the proximal right coronary artery. A surprise, in view of the normality of the chest x-ray findings, was a poorly contractile, thin-walled left ventricle with three to four times the normal volume. There was no evidence of a left-ventricular aneu-
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~~ ~
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MCCALLISTER
!'i
Y
i:
I~-"
I
!!
.~
:
[ll
;:;:
!ftl
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m l:;
Figure 3 (case 4). Electrocardiogram (50 mm/sec). Note small Q's in leads 11, Ill, aVF, and V 1-4; also intraventricular conduction delay - QRS duration = 0.10 sec.
rysm. The left-ventricular end-diastolic pressure was 25 mm Hg and the cardiac index was 3.2 liters/min/m2 • During supine leg exercise (100 kg-m/min) the leftventricular end-diastolic pressure rose to 37 mm Hg. Digitalis therapy, sodium restriction, and moderation in physical activities were advised.
Evaluation of Coronary Arteries in Valvular Heart Disease Some patients may have symptoms or electrocardiographic findings suggesting coronary-artery disease associated with valvular heart disease. In some cases, cardiac catheterization has revealed that the symptoms were due primarily to the coronary-artery disease, and anticipated valvular replacement was not necessary. Other patients with angina pectoris are found to have normal coronary arteries, though their valvular heart disease was severe; and it can be concluded that the surgical risk was less than previously thought. Some authors have stressed the value and importance of coronary arteriography in the investigation of angina pectoris associated with aortic stenosis. 13 Since aortic-valve surgery may involve coronary cannulation an.d perfusion, information about the state of the, coronary circulation might be of some help to the surgeon. To the present time, however, Mayo Clinic surgeons have not deemed this necessary. Although the presence of coronary-artery disease has not been considered a contraindication to aortic-valve replacement, it is possible that data from a larger group of patients would indicate that surgery in some patients with severe coronary-artery disease is inadvisable because of the higher surgical risk. At present, because selective coronary arteriography is generally more difficult and time-consuming in patients with calcific aortic-valve disease, coronary arteriography usually is performed in selected cases only. The following case illustrates the therapeutic dilemma posed by severe aortic stenosis associated with severe three-vessel coronaryartery disease. Despite the reluctance of the clinicians and surgeons to proceed with aortic-valve replacement, the patient has done well postoperatively.
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CASE 5. A 52-year-old man seen at the Mayo Clinic in January 1969 said that exertional dyspnea and angina pectoris had begun 3 years previously. In 1967 he had had congestive heart failure associated with severe anterior chest pain, and digitalis and diuretic therapy had been given. Thereafter the angina and dyspnea had continued in severe degree, and the patient had remained incapacitated. Physical examination revealed typical signs of severe aortic-valve stenosis. The electrocardiogram showed evidence of an old inferior-septal. scar and a right bundle-branch block. A roentgenogram showed marked left-ventricular hypertrophy, moderate dilatation of the ascending aorta, and moderate left-atrial hypertrophy. Coronary arteriography, left ventriculography, and measurement of the aorticvalve gradient were done to make possible a better assessment of the risks and benefits of aortic-valve replacement. Severe three-vessel coronary-artery disease was found, and thickening and decreased contractility of the left ventricular wall. The cardiac index was 2.3 liters!min/m2 , the aortic pressure 129/67 mm Hg, and the left-ventricular pressure 172/44 with an aortic-valve-orifice area of 0.3 sq. cm/m2 • It was thought that the patient had severe coronary-artery and myocardial disease as well as severe aortic stenosis. There was considerable concern about the risk of aortic-valve replacement, but it was offered because of the seriousness of the current disability. In May, a MacGovern-Cromie ball valve prosthesis was inserted successfully (by Dr. Gordon K. Danielson). The postoperative course was uneventful, and the patient has only rarely experienced angina subsequently. Roentgenograms made 3 months after operation showed that the heart size had decreased considerably.
Of prime importance is the assessment of myocardial function and the severity of coronary-artery disease in patients who have mitral-valve regurgitation in association with coronary-artery disease. Patients with mitral-valve incompetence associated with severe myocardial dysfunction do not usually benefit from mitral-valve replacement. 19
SELECTION OF PATIENTS FOR SURGICAL OR MEDICAL TREATMENT At the present time an argument can be made for studying the coronary anatomy in most patients with angina pectoris - particularly those under the age of 60-as a basis for proper planning of treatment. The young patient with multiple myocardial infarctions, even though without angina pectoris, probably should be studied, although most authorities are still reluctant to offer myocardial revascularization to the patient without symptomatic angina pectoris. However, as knowledge increases concerning the natural history of coronary-artery disease, it is apparent that angina is but one clinical manifestation of the pathologic process. When the clinician is faced with the decision regarding the selection of individual patients for coronary-artery surgery, certain epidemiologic and pathologic data must be considered. More than 500,000 patients die each year in the United States from coronary-artery disease; yet many patients live for years with their angina, and the clinical course is a variable one. Combining figures from the various studies on the
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subject, one may calculate the average survival after onset of angina as 4 years 2,23 and the average 5-year mortality rate as 30 to 40%.2,23 Although pathologic studies have shown that severe long-standing coronary-artery disease may lead to the development of collaterals without myocardial damage, many patients with an arteriographically demonstrated well-developed collateral circulation continue to have symptomatic and disabling angina. Medical therapy may afford considerable symptomatic relief to the patient with angina pectoris, but the longterm prognosis remains poor. Whereas the effects of myocardial revascularization on longevity are unknown, internal mammary implantation, direct repair of a stenosed coronary artery, and bypass vein-graft procedures have offered considerable promise initially. Internal mammary implantation brings clinical improvement in the majority of cases; but physiologically, direct coronary-artery surgery is more attractive. Though fewer than 10% of patients have a right coronary-artery lesion suitable for direct repair, the recent advances in bypass vein-grafting have increased the number of instances suitable for right coronary-artery surgery; and initial reports indicate t}lat techniques eventually will allow bypass for left coronary-artery lesions. It may become increasingly important to study patients with ischemic heart disease early - before the development of myocardial infarction and fibrosis. In addition to or in place of myocardial revascularization, arteriographic and physiologic studies in individual cases may indicate that myocardial revascularization should be supplemented or replaced by medication (with propranolol, vasodilators, digitalis, carotid-sinus stimulators), exercise programs, or resection of an occult left-ventricular aneurysm. Certain patients who clinically appear suitable for exercise programs may in fact be endangered by more than mild physical activity, as is illustrated by the following case. CASE 6. A 55-year-old insurance salesman seen at the Mayo Clinic in 1962 had a family history that included vascular disease and diabetes. The patient had had myocardial infarctions in 1957 and 1961. A weight-reduction diet and anticoagulant therapy were recommended. The patient was next seen in December 1967, when he came seeking advice concerning participation in a graduated exercise program at the YMCA. He had had an episode of coronary insufficiency in June 1966, and a third infarction had occurred in July 1967. Mild angina had been present since July 1967, but the patient continued to work full time. There was no history of heart failure. The electrocardiogram showed relics of an anterior-posterior myocardial infarction and a right bundle-branch block. The findings from the chest x-ray were normal. A coronary arteriogram revealed complete obstruction of the right coronary artery and severe stenosis of the left anterior descending coronary artery. One major branch of the left circumflex coronary artery was totally occluded and there were no good collaterals. The evidence from the ventriculogram was grossly abnormal, including marked generalized decrease in contractions. The leftventricular end-diastolic pressure at rest was 27 mm Hg. Because of the severe abnormality in left-ventricular function, it was thought inadvisable for the patient to enter into the YMCA exercise program; and indeed it was suggested that he restrict his activities and take digitalis.
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For intelligent planning of a therapeutic program for the patient with symptomatic ischemic heart disease, it helps the clinician to have information regarding the site and severity of the coronary-artery disease as well as data on myocardial function. Some patients have occult severe myocardial disease and borderline cardiac function secondary to coronary-artery disease, and yet roentgenography shows that the heart is of normal size. In such circumstances digitalis may be beneficial and propranolol may be contraindicated, as in the case described above. Resection of a left-ventricular aneurysm may produce clinical improvement in some cases of heart failure or intractable angina. A significant number of patients may die from progression of coronary-artery disease, however, within the first year following successful surgery. Eventually coronary arteriography may provide data to help in deciding for or against surgery in cases of left-ventricular aneurysm. The patient with single-vessel disease likely has a better prognosis than the patient with severe diffuse three-vessel disease, particularly if the collaterals are inadequate.
EVALUATION OF THERAPEUTIC RESULTS Surgical Postoperative coronary arteriographic studies are important for obtaining objective evidence of improvement following coronary-artery surgery. Although the majority of patients reported have described improvement in clinical symptoms after internal-mammary implantation,l° the objective evaluation of myocardial revascularization has been difficult and the operation has remained controversial. 21 McCallister and associates21 found objective evidence of successful revascularization in only 14 of 27 patients studied 1 year postoperatively. Although 22 of the group described moderate to marked clinical improvement, objective evidence of improvement in myocardial function could be found in only 4; and in individual cases there was poor correlation between the objective result and the change in symptoms reported by the patient. Important in evaluation of the overall clinical result were the change in degree of coronary-artery disease, the patency of the implant, the development of collateral circulation, and the left-ventriculographic changes accompanying the postoperative myocardial infarction that occurred in some cases. 12 From these studies it was concluded that internal-mammary implantation was beneficial to no more than 50% of the patients thus treated; and the need of further objective data for evaluating the results of myocardial revascularization procedures was emphasized. 21 CASE 7. A 48-year-old printer described angina pectoris of 2 years' duration requiring 10 to 35 nitroglycerin tablets daily. During the previous 6 months the angina had become more frequent and had come on readily after less than a half block of walking at a normal pace. Roentgenography showed the heart size was
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Figure 4 (case 7). A, Preoperative angiogram: right coronary artery in left anterior oblique view. High-grade stenosis is visualized in main trunk, involving proximal rightventricular branch. B, One year after patch-graft arterioplasty: right coronary artery in left anterior oblique view. Note filling of left anterior descending coronary artery via collaterals in lower right corner of picture.
normal, and electrocardiography showed a right bundle-branch block pattern. The physical findings were normal. Coronary arteriography demonstrated high-grade occlusion of the proximal right coronary artery (Fig. 4A), severe stenosis of the left anterior descending coronary artery with retrograde filling from the right coronary artery, and mild narrowing in the left circumflex coronary artery. The ventriculogram showed decreased apical-inferior contractions (Fig. 5A). In February 1968, right coronary-artery angioplasty and left internal-mammery-artery implantation were performed (by Dr. Robert B. Wallace). During the next year the patient experienced rare episodes of angina with extreme exertion. Coronary arteriography was performed 1 year postoperatively. The right coronary artery (Fig. 4B) and the left internal mammary implant were patent and had collaterals, and the ventriculogram was normal (Fig. 5B). There was no change in the other lesions observed previously. Hemodynamic studies had revealed abnormally high left-ventricular end-diastolic pressure during exercise preoperatively (33 mm Hg) but obtained a normal value (1 7 mm Hg) during exercise postoperatively (Table 3).
Figure 5 (case 7). Left-ventricular angiograms, right anterior oblique view, at end of systole. A, Preoperative: note abnormal decreased emptying in inferior apical portion. B, Postoperative: ventricular contraction appears normal.
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Table 3.
Hemodynamics at Rest and During Mild Supine Leg Exercise (C ase 7) PREOPERATIVE
Left-ventricular end-diastolic pressure, mmHg Stroke-volume index, mllm2 Heart rate (beats/min)
POSTOPERATIVE
(1 YR)
REST
EXERCISE*
REST
EXERCISE':'
11
33
12
17
57 60
40 81
64 54
53
72
':'100 kg-m/min for 3 minutes.
In this case objective evidence of improvement was observed in the postoperative arteriogram, ventriculogram, and left-ventricular hemodynamic data, in addition to the described improvement in clinical symptoms. Worthy of note was the return of the ventriculographic pattern to normal. So far as the author knows, this is the first reported case in which an abnormal ventriculogram has returned to normal after coronary-artery surgery. The result may reflect more effective revascularization by direct coronary-artery surgery than has been accomplished previously with internal-mammary-artery implantation alone.
Medical Although it still is usually a clinical investigator who employs coronary arteriography for evaluation of the effects of medical therapy, the clinical value of the technique in this application may be larger in the future. It has not been clearly established that exercise programs promote the development of collateral circulation in man, nor that antihyperlipidemic therapy causes the regression or prevents the progression of coronary-artery lesions. Serial studies of patients receiving medical therapy, similar to those used for the evaluation of surgical treatment, are presently under way.4.14 In some cases significant progression of coronary-artery disease over a period of 1 or 2 years despite a good medical program has prompted the author to advise surgical therapy. Studies of 27 patients before and 1 year after internal mammary artery implantation showed progression of the arteriographic lesions in 11 of them when the second study was carefully compared to the first. 21
SUMMARY Coronary arteriography is a reliable and important technique for the evaluation of patients with heart disease. Complications are remarkably uncommon in most laboratories with experience in cardiac catheterization. Detailed knowledge of the coronary anatomy has greatly improved our understanding of coronary-artery disease in the living patient, and has encouraged the development of surgical techniques to improve the myocardial circulation.
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Appropriate purposes for use of the technique include selection of patients for medical or surgical therapy, postoperative evaluation of surgical results, diagnostic explanation of chest pain, investigation of electrocardiographic abnormalities, clarification of ill-defined heart disease, and evaluation of the coronary circulation in patients with valvular heart disease. Other purposes for which its use may be justified are evaluation of the effect of medical therapy and selection of patients for resection of left-ventricular aneurysm. Relative contraindications to coronary arteriography at the present time are accelerated unstable angina of recent onset, recent myocardial infarction, and moderate obesity.
REFERENCES 1. Allison, R. B., Rodriguez, F. L., Higgins, E. A., Jr., Leddy, J.P., Abelmann, W. H., Ellis, L. B., and Robbins, S. L.: Clinicopathologic correlations in coronary atherosclerosis: Four hundred thirty patients studied with postmortem coronary angiography. Circulation 27:170-184 (Feb.) 1963. 2. Beard, O. W., Hipp, H. R., Robins, M., and Verzolini, V. R.: Initial myocardial infarction among veterans: Ten-year survival. Amer Heart J 73:317-321 (March) 1967. 3. Benchimol, A., and McNally, E. M.: Hemodynamic and electrocardiographic effects of selective coronary angiography in man. New Eng J Med 274: 1217-1224 (June 2) 1966. 4. Buchwald, H., Moore, R. B., Frantz, 1. D., Jr., Tuna, N., Baltaxe, H. A., Amplatz, K., and Varco, R. L.: Correlation of lipid levels and Fredrickson type, electrocardiograms and vectorcardiograms, clinical symptoms, and angiocardiograms in fifty partial ileal bypass patients. (Abstr.) Circulation 38(Suppl 6):48 (Oct.) 1968. 5. Campeau, L., Bourassa, M. G., Bois, M. A., Saltiel, ]., Lesperance, J., Rico, 0., Delcan, J-L., and Telleria, M.: Clinical significance of selective coronary cinearteriography. Canad Med Ass J 99: 1063-1068 (Dec. 7) 1968. 6. Campeau, L., Lesperance, J., Bourassa, M. G., and Ashekian, P. B.: Myocardial infarction without obstructive disease at coronary arteriography. Canad Med Ass J 99:837-843 (Nov. 2) 1968. 7. Cohen, L. S., Elliott, W. C., Klein, M. D., and Gorlin, R.: Coronary heart disease: Clinical, cinearteriographic and metabolic correlations. Amer J Cardiol 17: 153-168 (Feb.) 1966. 8. Cross, D. F.: Diverse etiology of angina pectoris. New Eng. J Med 275:1255 (Dec. 1) 1966. 9. Eliot, R. S., and Bratt, G.: The paradox of myocardial ischemia and necrosis in young women with normal coronary arteriograms: Relationship to abnormal hemoglobinoxygen dissociation. Amer J Cardiol 23 :633-638 (May) 1969. 10. Favaloro, R. G., Effier, D. B., Groves, L. K., Sones, F. M., Jr., and Fergusson, D. J. G.: Myocardial revascularization by internal mammary artery implant procedures: Clinical experience. J Thorac Cardiov Surg 54:359-368 (Sept.) 1967. 11. Gray, C. R., Hoffman, H. A., Hammond, W. S., Miller, K. L., and Oseasohn, R. 0.: Correlation of arteriographic and pathologic findings in the coronary arteries in man. Circulation 26:494-499 (Oct.) 1962. 12. Greenberg, B. H., McCallister, B. D., Frye, R. L., and Wallace, R. B.: Serum glutamic oxaloacetic transaminase and electrocardiographic changes after myocardial revascularization procedures in patients with coronary artery disease. Amer J Cardiol (In press.) 13. Hale, G., Dexter, D., Jefferson, K., and Leatham, A.: Value of coronary arteriography in the investigation of ischaemic heart disease. Brit Heart J 28:40-54, 1966. 14. Hellerstein, H. K., Hornsten, T. R., Goldbarg, A. N., Burlando, A. G., Friedman, E. H., Hirsch, E. Z., and Marik, Sue: The Influence of Active Conditioning Upon Coronary Atherosclerosis: A Progress Report. In Brest, A. N., and Moyer, J.H.: Atherosclerotic Vascular Disease: A Hahnemann Symposium. N ew York, Appleton-Century-Crofts, Inc., 1967, pp. 115-129. 15. Judkins, M. P.: Percutaneous transfemoral selective coronary arteriography. Radiol Clin N Amer 6:467-492 (Dec.) 1968. 16. Judkins, M. P.: Personal communication to the authors. 17. Kemp, H. G., Elliott, W. C., and Gorlin, R.: The anginal syndrome with normal coronary arteriography. Trans Ass Amer Physicians 80:59-68, 1967.
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18. Kemp, H. G., Evans, H., Elliott, W. C., and Gorlin, R.: Diagnostic accuracy of selective coronary cine-arteriography. Circulation 36:526-533 (Oct.) 1967. 19. McCallister, B. D.: Hemodynamic Studies. In Ellis, F. H., Jr.: Surgery for Acquired Mitral Valve Disease. Philadelphia, W. B. Saunders Company, 1967, pp. 114-132. 20. McCallister, B. D.: Electrocardiographic correlations with coronary arteriography in patients with coronary artery disease. Trans Ass Life· Insur Med Dir Amer 52: 162-168, 1968. :21. McCallister, B. D., Richmond, D. R.. Hallel'mann. F. J,. Wallace. R. B.. and Frve. R. L.: Left ventricular hemodynamics before and one year following internal mamm~ryartery implantation for angina pectoris. (Abstr.) Amer J Cardiol 23: 127 CJan.) 1969. 22. McCallister, B. D., Yipintsoi, T., Hallermann, F. J., Wallace, R. B., and Frye, R. L.: Left ventricular performance during mild supine leg exercise in coronary artery disease. Circulation 37:922-931 (June) 1968. 23. Pell, S., and D'Alonzo, C. A.: Immediate mortality and five-year survival of employed men with a first mvocardial infarction. New Eng J Med 270:915-922 (April 30) 1964. 24. Proudfit, W. L., Shirey, E. K., and Sones, F. M., Jr.: Selective cine coronary arteriography: Correlation with clinical findings in 1,000 patients. Circulation 33:901-910 (June) 1966. 25. Saltups, A., McCallister, B. D., Hallermann, F. J., Wallace, R. B., Smith, R. E., and Frye, R. L.: Left ventricular hemodynamics in patients with coronary artery disease and in normal subjects: Correlations with the extent of coronary artery lesions and the electrocardiogram. Amer J Med (In press.) 26. Shirey, E. K.: Correlative pathologic study of the coronary microcirculation with coronary arteriography. (Abstr.) Circulation 38(Suppl 6): 179 (Oct.) 1968. 27. Sones, F. M., Jr., and Shirey, E. K.: Cine coronary arteriography. Mod Conc Cardiov Dis 31 :735-738 (July) 1962.
Nearly two centuries have passed since Heberden's original description of angina pectoris; yet only within the last decade have methods been available to correlate clinical information with anatomic lesions of the coronary circulation in a living patient. Coronary arteriography, which has been largely responsible for our increased understanding of coronary-artery disease, is now an integral and essential part of the diagnostic evaluation of selected patients with heart disease in most cardiac-catheterization laboratories. The procedure can be performed consistently and with very little risk by appropriately trained personnel 15, 27 Coronary arteriography affords the clinician a method for defining the severity and degree of coronary-artery disease and selecting candidates for coronary-artery surgery. In addition, it is a means for determining the cause of diagnostic problems of chest pain as well as some types of myocardial disease. Coronary arteriography may be helpful also in the evaluation of patients whose coronary-artery disease is associated with other types of heart disease. In cases of valvular heart disease or ventricular aneurysm, the prognosis and surgical risk may be related to the extent of coronary-artery disease, which thus may be important in the selection of patients for surgery. Moreover, the clinical investigator has added new knowledge of the pathophysiology of coronary-artery disease by correlating findings at coronary arteriography with left-ventricular hemodynamics, electrocardiographic findings, and metabolic studies. The active interest in selecting patients for coronary-artery surgery has also afforded the epidemiologist a unique opportunity to follow the natural history of lesions in patients (usually those thought to be unsuitable for surgery) on medical regimens, such as exercise programs or anti-hyperlipidemic therapy.
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TECHNIQUE Cine coronary arteriography has been the method of choice in many laboratories because of its dynamic nature ,27 although techniques utilizing high-resolution serial radiography have depicted remarkable anatomic detail. 15 The method of Sones and Shirey, in which a woven catheter is introduced via a brachial-artery incision selectively into each coronary ostium, has been replaced in many laboratories by percutaneous transfemoral selective coronary arteriography as described by Judkins. 15 Either method is satisfactory and reliable in the hands of an appropriately trained cardiologist; in the author's opinion the transfemoral method is more readily learned by those inexperienced in usual cardiac catheterization techniques, but is also more readily subject to serious complications. It is clear that either technique is safest in the hands of those most experienced with it. Multiple oblique projections are necessary in order to delineate clearly the three dimensions of arteriographic lesions. A number of manufacturers provide excellent equipment for coronary arteriography. Servicing facilities should be of prime importance in the final choice for each laboratory. Adequate pictures have been recorded with 35-mm and with over-framed 16-mm cine techniques. The latter allow more room for technical error, the former can provide larger images. Nearperfect techniques in photography, roentgenology, and film development are required for producing the information necessary for clinical decisions. The moderately obese patient should not be studied by this means, as satisfactory films will rarely be obtained. Strict attention to detail is essential: (1) arterial pressures should be monitored from the tip of the catheter, (2) the electrocardiogram should be monitored continuously, (3) the catheter system must be flushed repeatedly to prevent formation of small fibrin clots, and (4) the catheter positioning must be meticulous in order to avoid obstruction of the coronary ostium or dissection of a coronary artery during injection. After each injection, abnormalities in the ST and T waves occur, as well as a drop in arterial pressure. 3 These should return to base-line status before further injections are performed. Methylglucamine diatrizoate (Renografin-76) has been reported15 to be associated with fewer serious ventricular dysrhythmias than diatrizoate sodium (Hypaque-M, 90%), and is favored by the author. It is essential that the coronary arteriographic study be under the direction of a physician familiar with cardiovascular hemodynamics and not be considered a radiologic procedure separated from the diagnostic cardiac laboratory. Many cases require hemodynamic data in addition to coronary arteriography for determining the presence or absence of valvular or subvalvular aortic stenosis, mitral-valve disease, or myocardial disease. Accurate measurements of left-ventricular function during rest and exercise may be essential in some cases (as illustrated by cases 2 and 3, below). Preferably, hemodynamic measurements should be made before or at least 30 minutes after the injection of con-
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trast media. Elevations of left-ventricular end-diastolic pressure above the base-line figure have been seen to persist for 15 to 20 minutes after coronary arteriography and left-ventricular angiography.
COMPLICATIONS Despite the serious hazards of coronary arteriography and the severity of the diseases involved, there have been remarkably few complications in most laboratories. Strict attention to details is important in the prevention of serious events such as ventricular fibrillation, ventricular tachycardia, or marked sinus bradycardia; and availability of resuscitative and defibrillating equipment makes possible the immediate control of these occasional arrhythmias. In the author's experience, atrial pacing has not been necessary if careful attention was given to catheter-tip monitoring, prompt withdrawal of a damped catheter to allow immediate washout of contrast material, and reduction of the amount of contrast material to the minimal amount required for adequate visualization of each coronary artery in individual patients. Using methylglucamine diatrizoate (Renografin-76), Judkins 15 did not encounter an arrhythmia other than the usual transient bradycardia with more than 7,000 coronary contrast injections. In the author's experience with the same contrast medium, ventricular fibrillation or tachycardia has occurred in approximately 1 % of patients. Death and myocardial infarction have rarely been related to coronary arteriography. The author has observed one patient with severe angina decubitus who developed a myocardial infarction 16 hours after the study and subsequently died. A second patient, whose angina was worsening, developed infarction after a period of hypotension that followed an injection into the left coronary artery; and he also died subsequently. A third patient experienced a 30-minute period of chest pain during coronary arteriography; and on the next day a slight rise in the serum glutamic transaminase concentration and inverted T waves in tracings from V5 and V6 were noted. It was thought that this patient had a subendocardial infarction, since no elevation of SGOT or electrocardiographic changes had been observed 24 hours after coronary arteriography in an initial series of 100 patients so studied by the author. It seems inadvisable to perform coronary arteriography when angina pectoris has worsened recently or when myocardial infarction has occurred within 4 to 6 months, except in selected cases. Recent success with direct coronary-artery surgery may lead to a change in this conservative approach in the future. Local thrombotic complications may develop at the site of the brachial arteriotomy, but significant compromise of the arm circulation is rare. Use of a Fogarty catheter to remove clots, both distally and proximally, prior to closure of the arteriotomy incision has greatly reduced the incidence of decreased radial pulse in the author's experience. Early consultation and exploration of an artery by a vascular surgeon is advisable if occlusion occurs with associated evidence of circulatory
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impairment. With transfemoral technique, thrombotic complications sometimes appear in the femoral artery and are usually related to intimal injury.15 From 1500 examinations Judkins 16 reported 0.6% had complications at the femoral puncture site, of which 0.4% were minor and 0.2% major (requiring ileofemoral surgery).
CLARIFICATION, EVALUATION, DIAGNOSIS Diagnostic Chest-Pain Problems SIGNIFICANCE OF A NORMAL CORONARY ARTERIOGRAM. Heretofore the clinical history and the electrocardiographic tracings made at rest and during exercise have been the primary means of detecting coronaryartery disease. However, some patients with severe coronary-artery disease may be normal electrocardiographically both at rest and during exercise;7,2o and in other cases the nature of the chest pain may be uncertain. Indeed, a number of patients with chest pain receive conflicting opinions from different physicians concerning its cause, and the cardiologist may be unable to make a secure diagnosis. The evidence from coronary arteriography, if normal, can exclude atheromatous disease of the major branches of the coronary arteries, which is the pathologic finding usually associated with angina pectoris. Coronary arteriography may be of great help in reassuring the cardiac neurotic and his physician that the chest pains are benign. CASE 1. A 38-year-old mechanic first seen at the Mayo Clinic in January 1967 had a family history of heart disease. A brother had died at age 48 of a heart attack and the patient's mother and father had developed angina at ages 50 and 65, respectively. For 2 years the patient had noted substernal and precordial chest pain with moderate exertion. A dull ache in the left side of the chest occurred sometimes with excitement and sometimes spontaneously, and its severity was increasing. At first the patient had noted the pain after a hard day's work, when eating or postprandially. A number of episodes had lasted 10 minutes and had been very severe. He had taken erythrityl tetranitrate (Cardilate), dipyridamole (Persantin), and chlordiazepoxide (Librium). The initial clinical impression was that the patient had ischemic heart disease with angina pectoris. During hospitalization for 10 days there was no change in his normal electrocardiographic pattern. Anticoagulants were prescribed. The history was reviewed on a number of occasions and it was thought that the patient may well have had angina pectoris in the past; but at the time of hospitalization he did not clearly describe typical exercise-induced pain. During and after treadmill exercise for 9 minutes on a 10-degree incline at 3 miles per hour, the electrocardiographic pattern was normal. The patient became hostile on occasions because "nothing was done" for his pain, and he continued to be obsessed with the idea that he would drop dead like his brother. A diagnosis of angina pectoris could not be made with any degree of confidence. Gastric and esophageal roentgenologic findings and tracings of esophageal motility were normal. Left ventriculography, exercise left-ventricular hemodynamic study, and coronary arteriography gave normal results. The patient subsequently returned to his work as a mechanic and, with strong reassurance from his physician, has achieved excellent rehabilitation.
Available data indicate that luminal narrowing of 20 to 25% may be undetected by coronary arteriography and that more severe narrowing
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may be difficult to detect if it is circumferential or cylindrica1. 5 , 11 Generally, the estimate of narrowing observed arteriographically may be 20 to 25% less than what is demonstrated post mortem. However, pathologic studies have shown that significant arteriographic findings are uncommon in asymptomatic individuals less than 45 to 50 years of age. 1 When symptoms of ischemic heart disease are present, the pathologic changes are severe and multiple, and mostly involve proximal vessels of calibers readily visualized by coronary arteriography.18 Proudfit and associates reported that they had not found symptoms of typical angina pectoris in patients whose luminal narrowing was less than 50%. Angina pectoris is known to occur with nonarteriosclerotic heart diseases. In patients whose coronary arteries were normal, angina has accompanied valvular heart disease, myocardial disease (particularly obstructive cardiomyopathy), and various forms of pulmonary hypertension. 8 It is important that these diseases be excluded clinically or by cardiac catheterization. Only rarely have normal coronary arteriographic findings been obtained from patients with a proved history of a myocardial infarction, and the explanation for these exceptional cases is not clear. They could represent a twig occlusion in the absence of significant disease. Other cases may be results of embolic infarction from valvular lesions or prostheses. 6 Therefore a normal coronary arteriogram is strong evidence against ischemic heart disease in the patient under 50. Conversely, coronary-artery lesions are seen in a large segment of the population beyond 60 years of age, and it is hazardous to attribute complaints of atypical chest pain to ischemic heart disease in older patients, particularly those with minor lesions. Eliot and Bratt have described a group of women with symptoms of angina pectoris but normal coronary arteriograms who had abnormal oxygen-hemoglobin dissociation curves. As yet these observations remain unconfirmed by other investigators. Kemp and associates 17 also have reported a group of patients with typical angina pectoris and normal coronary arteriograms. Abnormality of the electrocardiographic tracing during exercise and an abnormality in lactate metabolism led the investigators to speculate that the angina in these patients may be related to a microangiopathy not detectable by coronary arteriography. Shirey has performed transthoracic myocardial biopsy on patients with normal coronary arteriograms and has concluded that coronary arteriography is a dependable technique for detection of coronary atherosclerosis. Disease of small myocardial vessels may occur in association with certain muscular dystrophies and collagen diseases, but the presence of these systemic disorders is usually apparent clinically from other evidence. Although the paradox of a normal coronary arteriogram in a case of angina pectoris is often explained by cardiac neurosis, a few such cases remain without explanation. At the Mayo Clinic, of 54 patients studied primarily because of diagnostic chest pain, 44 had normal coronary arteriograms, 8 had arteriographic evidence of severe coronary-artery disease, and 2 had evidence of myocardial disease in their ventriculograms and exercise left-ventricular hemodynamic values. The 44 pa-
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tients with normal coronary arteriograms also had normal left ventriculograms and normal exercise hemodynamics. 22 ,25 It is the author's opinion that if the coronary arteriogram, the left ventriculogram, and the left-ventricular exercise hemodynamics are normal, the patient can be assured that he does not have significant coronary-artery or myocardial disease. The patient can be further assured that his symptoms are benign and not related to the type of vascular disease (atherosclerosis) ordinarily associated with symptoms of myocardial ischemia. ELECTROCARDIOGRAPHIC ABNORMALITIES. Certain patients have unexplained electrocardiographic abnormalities that may reduce their opportunity to obtain insurance, to engage in certain professions, and to live a life free of concern about serious occult cardiac disease. One of the 54 patients mentioned above, who had an intermittent rate-dependent left bundle-branch block, was thought by the clinicians responsible for her to have coronary-artery disease; but coronary arteriography revealed no evidence of it, and the patient and her referring physician were reassured in this regard. CASE 2. A 41-year-old airline pilot first seen at the Mayo Clinic in June 1969 described an episode of substernal distress radiating to the chest and arms which had occurred in 1966 while he was flying. The discomfort was associated with difficulty in breathing and had continued intermittently for 20 minutes. These symptoms had caused him to land his aircraft before finishing the planned flight. An electrocardiogram taken subsequently had been interpreted as showing evidence of an old myocardial infarction. At this institution the physical findings were entirely normal. There were no cardiac murmurs at rest or after inhalation of amyl nitrite or on performance of the Valsalva maneuver. The electrocardiogram (Fig. 1) showed a depolarization pattern which suggested septal hypertrophy or perhaps a conduction aberration involving the posterior inferior ramification of the left bundle branch. The electrocardiographic tracings dating back to 1962 were identical to those made in 1966 and 1969. Because the patient was grounded by the Federal Aviation Administration, he requested a complete cardiac evaluation; and cardiac catheterization, including coronary arteriography, was performed in July 1969. The results of the catheterization study (Table 1) were somewhat surprising. There was no gradient across the left-ventricular outflow tract at rest or during exercise. The left-ventricular cineangiogram showed left-ventricular and probable septal hypertrophy, and it was thought that the deep Q's in leads 2 and 3, aVf, and V5 and V6 most likely reflected septal hypertrophy. (Worthy of note is the fact that electrocardiographic examination of the patient's mother in June 1969 produced an identical pattern of depolarization.) The final diagnosis was myocardiopathy, hyperdynamic type, without obstruction.
Table 1.
Hemodynamics at Rest and During Exercise (Case 2)
Left-ventricular pressure, mm Hg Left-ventricular dp/dt Cardiac index (L/min/m2 ) Stroke-volume index (mllm2 )
3
3
MIN HARD
AT REST, ON BICYCLE ERGOMETER
MIN MILD EXERCISE, 100 KG-M/MIN
EXERCISE, 300 KG-M/MIN
133/8-24 3373 3.3 46
142/12-28 3234 3.8 43
157/9-32 3650 4.2 42
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Figure 1 (case 2). Electrocardiogram (50 mm/sec) and vectorcardiogram. Note deep Q's in leads 11, Ill, aVf, and Vi) andVfj. Initial forces are anterior, to the right and upward.
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In the future the expert consultant in insurance, industrial, and aviation medicine will likely be faced with a number of challenging cases in which the resting and exercise electrocardiograms show equivocal changes, yet physiologic and coronary arteriographic data are normal. It is hoped that the patients without significant evidence of heart disease will be managed accordingly.
Ill-Defined Heart Disease Patients who present with various combinations of atypical chest pain and abnormalities among the physical, roentgenologic, and electrocardiographic findings may puzzle the clinician as to the cause of the suspected heart disease. Physiologic data, in addition to radiologic, are essential in the evaluation of these patients with ill-defined heart disease and of those considered to have clinical variants of ischemic heart disease, as is illustrated by the following two cases. CASE 3. A 59-year-old woman seen at the Mayo Clinic in August 1969 had had two episodes of chest pain diagnosed as myocardial infarction - one in 1954 and one in 1962. For 2 years the patient had experienced moderate angina pectoris with exertion and occasionally at rest. She also reported having had vague and atypical syncopal episodes over 10 years, mild pedal edema, and occasional nocturnal coughing and dyspnea. The patient was taking many cardiac medicaments. There was a family history of diabetes mellitus. One brother had had coronaryartery surgery for severe ischemic heart disease. The patient also had a history of poorly controlled hypertension and had diabetes mellitus requiring insulin therapy. The serum cholesterol measured 454 mg/100 ml and the serum triglycerides 287. Although the chest roentgenogram showed the heart as not enlarged, the electrocardiogram indicated left-ventricular hypertrophy, but without evidence of previous myocardial infarction. Physical examination revealed blood pressure of 235/110 initially and 192/102 later. The carotid upstroke was rapid and bifid. There was a grade 1/6 short midsystolic left-sternal-border murmur. After the Valsalva maneuver the murmur increased to grade 2+/6, and after administration of amyl nitrite it increased to grade 3/6 with a higher pitch. Because of the hypertension, diabetes mellitus, and family history, coronaryartery disease was strongly suspected; but the possibility of obstructive cardiomyopathy was suggested by the physical findings. The carotid tracing showed a tidal wave suggested of obstructive cardiomyopathy. Coronary arteriography and left-heart catheterization were done (Table 2). The coronary arteriogram was normal. The left ventriculogram showed marked
Table 2.
Hemodynamic Data Under Control Conditions and After Administration of Isoproterenol (Case 3)
Femoral-artery pressure, mm Hg Left-ventricular pressure, mm Hg Cardiac output, L/min
UNDER CONTROL CONDITIONS
AFTER INFUSION OF ISOPROTERENOL (0.04 IJ-G/KG/MIN)
215/68 198/6-15 4.8
192/68 31/-2 to 15 5.5
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Figure 2 (case 4). within normal limits.
987
Normal cardiothoracic ratio: left-ventricular contour is generous, but
concentric hypertrophy of the left ventricle with narrowing of the left-ventricular outflow tract during systole, characteristic of idiopathic hypertrophic subaortic stenosis. Propranolol therapy brought a decrease in the intensity of the murmur and improvement in the clinical symptoms.
Noteworthy is the fact that five patients who had a diagnosis of coronary-artery disease and were referred to the Mayo Clinic for coronary arteriography have been demonstrated to have idiopathic hypertrophic subaortic stenosis. At the time of the hemodynamic study one of these had both idiopathic hypertrophic subaortic stenosis and significant coronary-artery disease. CASE 4. A 46-year-old man who came to the Mayo Clinic in September 1967 had had episodes of chest pain at ages 37 and 42 which had been diagnosed as myocardial infarctions. Thereafter, he had been free of symptoms until April 1967, when he had had three episodes of acute dyspnea, each of which occurred while he was playing golf. At the time of admission the roentgenographic silhouette of the heart was normal (Fig. 2). The electrocardiogram showed evidence of old anteroseptal and possible inferior scars (Fig. 3). There was a loud third heart sound but no definite murmur. In October coronary-arteriography revealed severe stenoses of the left anterior descending and left circumflex coronary arteries and complete occlusion of the proximal right coronary artery. A surprise, in view of the normality of the chest x-ray findings, was a poorly contractile, thin-walled left ventricle with three to four times the normal volume. There was no evidence of a left-ventricular aneu-
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MCCALLISTER
!'i
Y
i:
I~-"
I
!!
.~
:
[ll
;:;:
!ftl
;
I;
:~
H~
'I
,:
..
m l:;
Figure 3 (case 4). Electrocardiogram (50 mm/sec). Note small Q's in leads 11, Ill, aVF, and V 1-4; also intraventricular conduction delay - QRS duration = 0.10 sec.
rysm. The left-ventricular end-diastolic pressure was 25 mm Hg and the cardiac index was 3.2 liters/min/m2 • During supine leg exercise (100 kg-m/min) the leftventricular end-diastolic pressure rose to 37 mm Hg. Digitalis therapy, sodium restriction, and moderation in physical activities were advised.
Evaluation of Coronary Arteries in Valvular Heart Disease Some patients may have symptoms or electrocardiographic findings suggesting coronary-artery disease associated with valvular heart disease. In some cases, cardiac catheterization has revealed that the symptoms were due primarily to the coronary-artery disease, and anticipated valvular replacement was not necessary. Other patients with angina pectoris are found to have normal coronary arteries, though their valvular heart disease was severe; and it can be concluded that the surgical risk was less than previously thought. Some authors have stressed the value and importance of coronary arteriography in the investigation of angina pectoris associated with aortic stenosis. 13 Since aortic-valve surgery may involve coronary cannulation an.d perfusion, information about the state of the, coronary circulation might be of some help to the surgeon. To the present time, however, Mayo Clinic surgeons have not deemed this necessary. Although the presence of coronary-artery disease has not been considered a contraindication to aortic-valve replacement, it is possible that data from a larger group of patients would indicate that surgery in some patients with severe coronary-artery disease is inadvisable because of the higher surgical risk. At present, because selective coronary arteriography is generally more difficult and time-consuming in patients with calcific aortic-valve disease, coronary arteriography usually is performed in selected cases only. The following case illustrates the therapeutic dilemma posed by severe aortic stenosis associated with severe three-vessel coronaryartery disease. Despite the reluctance of the clinicians and surgeons to proceed with aortic-valve replacement, the patient has done well postoperatively.
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CASE 5. A 52-year-old man seen at the Mayo Clinic in January 1969 said that exertional dyspnea and angina pectoris had begun 3 years previously. In 1967 he had had congestive heart failure associated with severe anterior chest pain, and digitalis and diuretic therapy had been given. Thereafter the angina and dyspnea had continued in severe degree, and the patient had remained incapacitated. Physical examination revealed typical signs of severe aortic-valve stenosis. The electrocardiogram showed evidence of an old inferior-septal. scar and a right bundle-branch block. A roentgenogram showed marked left-ventricular hypertrophy, moderate dilatation of the ascending aorta, and moderate left-atrial hypertrophy. Coronary arteriography, left ventriculography, and measurement of the aorticvalve gradient were done to make possible a better assessment of the risks and benefits of aortic-valve replacement. Severe three-vessel coronary-artery disease was found, and thickening and decreased contractility of the left ventricular wall. The cardiac index was 2.3 liters!min/m2 , the aortic pressure 129/67 mm Hg, and the left-ventricular pressure 172/44 with an aortic-valve-orifice area of 0.3 sq. cm/m2 • It was thought that the patient had severe coronary-artery and myocardial disease as well as severe aortic stenosis. There was considerable concern about the risk of aortic-valve replacement, but it was offered because of the seriousness of the current disability. In May, a MacGovern-Cromie ball valve prosthesis was inserted successfully (by Dr. Gordon K. Danielson). The postoperative course was uneventful, and the patient has only rarely experienced angina subsequently. Roentgenograms made 3 months after operation showed that the heart size had decreased considerably.
Of prime importance is the assessment of myocardial function and the severity of coronary-artery disease in patients who have mitral-valve regurgitation in association with coronary-artery disease. Patients with mitral-valve incompetence associated with severe myocardial dysfunction do not usually benefit from mitral-valve replacement. 19
SELECTION OF PATIENTS FOR SURGICAL OR MEDICAL TREATMENT At the present time an argument can be made for studying the coronary anatomy in most patients with angina pectoris - particularly those under the age of 60-as a basis for proper planning of treatment. The young patient with multiple myocardial infarctions, even though without angina pectoris, probably should be studied, although most authorities are still reluctant to offer myocardial revascularization to the patient without symptomatic angina pectoris. However, as knowledge increases concerning the natural history of coronary-artery disease, it is apparent that angina is but one clinical manifestation of the pathologic process. When the clinician is faced with the decision regarding the selection of individual patients for coronary-artery surgery, certain epidemiologic and pathologic data must be considered. More than 500,000 patients die each year in the United States from coronary-artery disease; yet many patients live for years with their angina, and the clinical course is a variable one. Combining figures from the various studies on the
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subject, one may calculate the average survival after onset of angina as 4 years 2,23 and the average 5-year mortality rate as 30 to 40%.2,23 Although pathologic studies have shown that severe long-standing coronary-artery disease may lead to the development of collaterals without myocardial damage, many patients with an arteriographically demonstrated well-developed collateral circulation continue to have symptomatic and disabling angina. Medical therapy may afford considerable symptomatic relief to the patient with angina pectoris, but the longterm prognosis remains poor. Whereas the effects of myocardial revascularization on longevity are unknown, internal mammary implantation, direct repair of a stenosed coronary artery, and bypass vein-graft procedures have offered considerable promise initially. Internal mammary implantation brings clinical improvement in the majority of cases; but physiologically, direct coronary-artery surgery is more attractive. Though fewer than 10% of patients have a right coronary-artery lesion suitable for direct repair, the recent advances in bypass vein-grafting have increased the number of instances suitable for right coronary-artery surgery; and initial reports indicate t}lat techniques eventually will allow bypass for left coronary-artery lesions. It may become increasingly important to study patients with ischemic heart disease early - before the development of myocardial infarction and fibrosis. In addition to or in place of myocardial revascularization, arteriographic and physiologic studies in individual cases may indicate that myocardial revascularization should be supplemented or replaced by medication (with propranolol, vasodilators, digitalis, carotid-sinus stimulators), exercise programs, or resection of an occult left-ventricular aneurysm. Certain patients who clinically appear suitable for exercise programs may in fact be endangered by more than mild physical activity, as is illustrated by the following case. CASE 6. A 55-year-old insurance salesman seen at the Mayo Clinic in 1962 had a family history that included vascular disease and diabetes. The patient had had myocardial infarctions in 1957 and 1961. A weight-reduction diet and anticoagulant therapy were recommended. The patient was next seen in December 1967, when he came seeking advice concerning participation in a graduated exercise program at the YMCA. He had had an episode of coronary insufficiency in June 1966, and a third infarction had occurred in July 1967. Mild angina had been present since July 1967, but the patient continued to work full time. There was no history of heart failure. The electrocardiogram showed relics of an anterior-posterior myocardial infarction and a right bundle-branch block. The findings from the chest x-ray were normal. A coronary arteriogram revealed complete obstruction of the right coronary artery and severe stenosis of the left anterior descending coronary artery. One major branch of the left circumflex coronary artery was totally occluded and there were no good collaterals. The evidence from the ventriculogram was grossly abnormal, including marked generalized decrease in contractions. The leftventricular end-diastolic pressure at rest was 27 mm Hg. Because of the severe abnormality in left-ventricular function, it was thought inadvisable for the patient to enter into the YMCA exercise program; and indeed it was suggested that he restrict his activities and take digitalis.
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For intelligent planning of a therapeutic program for the patient with symptomatic ischemic heart disease, it helps the clinician to have information regarding the site and severity of the coronary-artery disease as well as data on myocardial function. Some patients have occult severe myocardial disease and borderline cardiac function secondary to coronary-artery disease, and yet roentgenography shows that the heart is of normal size. In such circumstances digitalis may be beneficial and propranolol may be contraindicated, as in the case described above. Resection of a left-ventricular aneurysm may produce clinical improvement in some cases of heart failure or intractable angina. A significant number of patients may die from progression of coronary-artery disease, however, within the first year following successful surgery. Eventually coronary arteriography may provide data to help in deciding for or against surgery in cases of left-ventricular aneurysm. The patient with single-vessel disease likely has a better prognosis than the patient with severe diffuse three-vessel disease, particularly if the collaterals are inadequate.
EVALUATION OF THERAPEUTIC RESULTS Surgical Postoperative coronary arteriographic studies are important for obtaining objective evidence of improvement following coronary-artery surgery. Although the majority of patients reported have described improvement in clinical symptoms after internal-mammary implantation,l° the objective evaluation of myocardial revascularization has been difficult and the operation has remained controversial. 21 McCallister and associates21 found objective evidence of successful revascularization in only 14 of 27 patients studied 1 year postoperatively. Although 22 of the group described moderate to marked clinical improvement, objective evidence of improvement in myocardial function could be found in only 4; and in individual cases there was poor correlation between the objective result and the change in symptoms reported by the patient. Important in evaluation of the overall clinical result were the change in degree of coronary-artery disease, the patency of the implant, the development of collateral circulation, and the left-ventriculographic changes accompanying the postoperative myocardial infarction that occurred in some cases. 12 From these studies it was concluded that internal-mammary implantation was beneficial to no more than 50% of the patients thus treated; and the need of further objective data for evaluating the results of myocardial revascularization procedures was emphasized. 21 CASE 7. A 48-year-old printer described angina pectoris of 2 years' duration requiring 10 to 35 nitroglycerin tablets daily. During the previous 6 months the angina had become more frequent and had come on readily after less than a half block of walking at a normal pace. Roentgenography showed the heart size was
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Figure 4 (case 7). A, Preoperative angiogram: right coronary artery in left anterior oblique view. High-grade stenosis is visualized in main trunk, involving proximal rightventricular branch. B, One year after patch-graft arterioplasty: right coronary artery in left anterior oblique view. Note filling of left anterior descending coronary artery via collaterals in lower right corner of picture.
normal, and electrocardiography showed a right bundle-branch block pattern. The physical findings were normal. Coronary arteriography demonstrated high-grade occlusion of the proximal right coronary artery (Fig. 4A), severe stenosis of the left anterior descending coronary artery with retrograde filling from the right coronary artery, and mild narrowing in the left circumflex coronary artery. The ventriculogram showed decreased apical-inferior contractions (Fig. 5A). In February 1968, right coronary-artery angioplasty and left internal-mammery-artery implantation were performed (by Dr. Robert B. Wallace). During the next year the patient experienced rare episodes of angina with extreme exertion. Coronary arteriography was performed 1 year postoperatively. The right coronary artery (Fig. 4B) and the left internal mammary implant were patent and had collaterals, and the ventriculogram was normal (Fig. 5B). There was no change in the other lesions observed previously. Hemodynamic studies had revealed abnormally high left-ventricular end-diastolic pressure during exercise preoperatively (33 mm Hg) but obtained a normal value (1 7 mm Hg) during exercise postoperatively (Table 3).
Figure 5 (case 7). Left-ventricular angiograms, right anterior oblique view, at end of systole. A, Preoperative: note abnormal decreased emptying in inferior apical portion. B, Postoperative: ventricular contraction appears normal.
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Table 3.
Hemodynamics at Rest and During Mild Supine Leg Exercise (C ase 7) PREOPERATIVE
Left-ventricular end-diastolic pressure, mmHg Stroke-volume index, mllm2 Heart rate (beats/min)
POSTOPERATIVE
(1 YR)
REST
EXERCISE*
REST
EXERCISE':'
11
33
12
17
57 60
40 81
64 54
53
72
':'100 kg-m/min for 3 minutes.
In this case objective evidence of improvement was observed in the postoperative arteriogram, ventriculogram, and left-ventricular hemodynamic data, in addition to the described improvement in clinical symptoms. Worthy of note was the return of the ventriculographic pattern to normal. So far as the author knows, this is the first reported case in which an abnormal ventriculogram has returned to normal after coronary-artery surgery. The result may reflect more effective revascularization by direct coronary-artery surgery than has been accomplished previously with internal-mammary-artery implantation alone.
Medical Although it still is usually a clinical investigator who employs coronary arteriography for evaluation of the effects of medical therapy, the clinical value of the technique in this application may be larger in the future. It has not been clearly established that exercise programs promote the development of collateral circulation in man, nor that antihyperlipidemic therapy causes the regression or prevents the progression of coronary-artery lesions. Serial studies of patients receiving medical therapy, similar to those used for the evaluation of surgical treatment, are presently under way.4.14 In some cases significant progression of coronary-artery disease over a period of 1 or 2 years despite a good medical program has prompted the author to advise surgical therapy. Studies of 27 patients before and 1 year after internal mammary artery implantation showed progression of the arteriographic lesions in 11 of them when the second study was carefully compared to the first. 21
SUMMARY Coronary arteriography is a reliable and important technique for the evaluation of patients with heart disease. Complications are remarkably uncommon in most laboratories with experience in cardiac catheterization. Detailed knowledge of the coronary anatomy has greatly improved our understanding of coronary-artery disease in the living patient, and has encouraged the development of surgical techniques to improve the myocardial circulation.
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Appropriate purposes for use of the technique include selection of patients for medical or surgical therapy, postoperative evaluation of surgical results, diagnostic explanation of chest pain, investigation of electrocardiographic abnormalities, clarification of ill-defined heart disease, and evaluation of the coronary circulation in patients with valvular heart disease. Other purposes for which its use may be justified are evaluation of the effect of medical therapy and selection of patients for resection of left-ventricular aneurysm. Relative contraindications to coronary arteriography at the present time are accelerated unstable angina of recent onset, recent myocardial infarction, and moderate obesity.
REFERENCES 1. Allison, R. B., Rodriguez, F. L., Higgins, E. A., Jr., Leddy, J.P., Abelmann, W. H., Ellis, L. B., and Robbins, S. L.: Clinicopathologic correlations in coronary atherosclerosis: Four hundred thirty patients studied with postmortem coronary angiography. Circulation 27:170-184 (Feb.) 1963. 2. Beard, O. W., Hipp, H. R., Robins, M., and Verzolini, V. R.: Initial myocardial infarction among veterans: Ten-year survival. Amer Heart J 73:317-321 (March) 1967. 3. Benchimol, A., and McNally, E. M.: Hemodynamic and electrocardiographic effects of selective coronary angiography in man. New Eng J Med 274: 1217-1224 (June 2) 1966. 4. Buchwald, H., Moore, R. B., Frantz, 1. D., Jr., Tuna, N., Baltaxe, H. A., Amplatz, K., and Varco, R. L.: Correlation of lipid levels and Fredrickson type, electrocardiograms and vectorcardiograms, clinical symptoms, and angiocardiograms in fifty partial ileal bypass patients. (Abstr.) Circulation 38(Suppl 6):48 (Oct.) 1968. 5. Campeau, L., Bourassa, M. G., Bois, M. A., Saltiel, ]., Lesperance, J., Rico, 0., Delcan, J-L., and Telleria, M.: Clinical significance of selective coronary cinearteriography. Canad Med Ass J 99: 1063-1068 (Dec. 7) 1968. 6. Campeau, L., Lesperance, J., Bourassa, M. G., and Ashekian, P. B.: Myocardial infarction without obstructive disease at coronary arteriography. Canad Med Ass J 99:837-843 (Nov. 2) 1968. 7. Cohen, L. S., Elliott, W. C., Klein, M. D., and Gorlin, R.: Coronary heart disease: Clinical, cinearteriographic and metabolic correlations. Amer J Cardiol 17: 153-168 (Feb.) 1966. 8. Cross, D. F.: Diverse etiology of angina pectoris. New Eng. J Med 275:1255 (Dec. 1) 1966. 9. Eliot, R. S., and Bratt, G.: The paradox of myocardial ischemia and necrosis in young women with normal coronary arteriograms: Relationship to abnormal hemoglobinoxygen dissociation. Amer J Cardiol 23 :633-638 (May) 1969. 10. Favaloro, R. G., Effier, D. B., Groves, L. K., Sones, F. M., Jr., and Fergusson, D. J. G.: Myocardial revascularization by internal mammary artery implant procedures: Clinical experience. J Thorac Cardiov Surg 54:359-368 (Sept.) 1967. 11. Gray, C. R., Hoffman, H. A., Hammond, W. S., Miller, K. L., and Oseasohn, R. 0.: Correlation of arteriographic and pathologic findings in the coronary arteries in man. Circulation 26:494-499 (Oct.) 1962. 12. Greenberg, B. H., McCallister, B. D., Frye, R. L., and Wallace, R. B.: Serum glutamic oxaloacetic transaminase and electrocardiographic changes after myocardial revascularization procedures in patients with coronary artery disease. Amer J Cardiol (In press.) 13. Hale, G., Dexter, D., Jefferson, K., and Leatham, A.: Value of coronary arteriography in the investigation of ischaemic heart disease. Brit Heart J 28:40-54, 1966. 14. Hellerstein, H. K., Hornsten, T. R., Goldbarg, A. N., Burlando, A. G., Friedman, E. H., Hirsch, E. Z., and Marik, Sue: The Influence of Active Conditioning Upon Coronary Atherosclerosis: A Progress Report. In Brest, A. N., and Moyer, J.H.: Atherosclerotic Vascular Disease: A Hahnemann Symposium. N ew York, Appleton-Century-Crofts, Inc., 1967, pp. 115-129. 15. Judkins, M. P.: Percutaneous transfemoral selective coronary arteriography. Radiol Clin N Amer 6:467-492 (Dec.) 1968. 16. Judkins, M. P.: Personal communication to the authors. 17. Kemp, H. G., Elliott, W. C., and Gorlin, R.: The anginal syndrome with normal coronary arteriography. Trans Ass Amer Physicians 80:59-68, 1967.
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18. Kemp, H. G., Evans, H., Elliott, W. C., and Gorlin, R.: Diagnostic accuracy of selective coronary cine-arteriography. Circulation 36:526-533 (Oct.) 1967. 19. McCallister, B. D.: Hemodynamic Studies. In Ellis, F. H., Jr.: Surgery for Acquired Mitral Valve Disease. Philadelphia, W. B. Saunders Company, 1967, pp. 114-132. 20. McCallister, B. D.: Electrocardiographic correlations with coronary arteriography in patients with coronary artery disease. Trans Ass Life· Insur Med Dir Amer 52: 162-168, 1968. :21. McCallister, B. D., Richmond, D. R.. Hallel'mann. F. J,. Wallace. R. B.. and Frve. R. L.: Left ventricular hemodynamics before and one year following internal mamm~ryartery implantation for angina pectoris. (Abstr.) Amer J Cardiol 23: 127 CJan.) 1969. 22. McCallister, B. D., Yipintsoi, T., Hallermann, F. J., Wallace, R. B., and Frye, R. L.: Left ventricular performance during mild supine leg exercise in coronary artery disease. Circulation 37:922-931 (June) 1968. 23. Pell, S., and D'Alonzo, C. A.: Immediate mortality and five-year survival of employed men with a first mvocardial infarction. New Eng J Med 270:915-922 (April 30) 1964. 24. Proudfit, W. L., Shirey, E. K., and Sones, F. M., Jr.: Selective cine coronary arteriography: Correlation with clinical findings in 1,000 patients. Circulation 33:901-910 (June) 1966. 25. Saltups, A., McCallister, B. D., Hallermann, F. J., Wallace, R. B., Smith, R. E., and Frye, R. L.: Left ventricular hemodynamics in patients with coronary artery disease and in normal subjects: Correlations with the extent of coronary artery lesions and the electrocardiogram. Amer J Med (In press.) 26. Shirey, E. K.: Correlative pathologic study of the coronary microcirculation with coronary arteriography. (Abstr.) Circulation 38(Suppl 6): 179 (Oct.) 1968. 27. Sones, F. M., Jr., and Shirey, E. K.: Cine coronary arteriography. Mod Conc Cardiov Dis 31 :735-738 (July) 1962.