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Cardiac Catheterization in Heart Disease
Cardiac Catheterization in Heart Disease TRUMAN G. SCHNABEL, JR., M.D. *
HUMAN cardiac catheterization was first performed twenty-five years ago by Forssman,1 using himself as a subject. Although his purpose was to introduce drugs directly into the cardiac chambers, the method has become far more important as a means of acquiring data that had never before been obtained in man. These data have contributed greatly to our understanding of normal and abnormal cardiovascular dynamics. They have led to more accurate diagnosis in both congenital and acquired heart disease and have been of value in the study of many types of cardiac therapy.
TECHNIQUE
Today the technique of catheterization of the right side of the heart is more complex than that which Forssman described in 1929. Radiopaque catheters are inserted through a peripheral vein (usually the basilic vein in the right or left antecubital fossa) after exposure of the vein. When a basilic vein of suitable size cannot be found, the saphenous vein is often used. Local anestheHia is ordinarily used at the site of insertion in adults, but general anesthesia is often required in children and infants. Once the catheter has been inserted into a peripheral vein, it is then directed under fluoroscopic guidance through the great veins, the right atrium, the right ventricle and finally into the pulmonary artery. Pressure measurements may be made and blood samples obtained from any of these sites. Whereas formerly mean pressures were recorded with a saline or mercury manometer, it is customary today to use manometric systems capable of recording accurately the entire pulse pressure curve. 2 , 3 The oxygen content of the blood is usually analyzed From the Robinette Foundation and the Department of Medicine, Hospital of the University of Pennsylvania.
* Assistant Professor of Medicine and Markle Scholar, University of Pennsylvania School of Medicine; Staff Member, Robinette Foundation, Hospital of University of Pennsylvania, Philadelphia. 1617
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manometrically by the technique of Van Slyke and Neill. 4 In some laboratories oxygen saturations are recorded rapidly by means of the whole blood cuvette oximeter,5 a technique which gives immediate results to the physician performing the study. This method has the added advantage of utilizing small samples of blood for each determination, thus making possible the analysis of many more samples on a patient. Foreign substances such as Evans blue," 7 fluorescein 8 or radiopaque materials may be injected through the catheter into the chambers of the right side of the heart or into the pulmonary artery. Dye dilution curves, circulation times and angiocardiograms obtained in this way are of further aid in the study of many hemodynamic problems. Until recently, direct information concerning the left side of the heart was obtained only when the catheter passed through an intracardiac defect. Because of the importance of acquiring data on the pressure changes occurring within this side of the heart it is now customary during venous catheterization to advance the catheter into a branch of the pulmonary artery until its tip is actually wedged in a small vessel. 9. 10 In this position the small pulmonary vessel becomes an extension of the catheter, so that the recorded pressure is probably fairly representative of the pressure pulse curve occurring in the pulmonary veins and left atrium. Other approaches to the recording of left atrial pressures have recently been demonstrated. These methods involve puncture of the left atrium directly with a small needle. In one method the needle is inserted through the right main bronchus into the left atrium under bronchoscopic visualization ill in the other technique the needle is introduced posteriorly through the eighth or ninth intercostal space percutaneously into the left atrium. 12 In the latter instance a small plastic catheter may be inserted through the needle into the left atrium and advanced into the left ventricle.l 3 The recording of left ventricular and central aortic pressure pulse curves has also been accomplished by retrograde, arterial catheterization. 14 In this method either a venous or a small plastic catheter may be used. The venous type of catheter is inserted into the arterial bed through an exposed peripheral vessel, whereas the small plastic catheter enters the peripheral artery through a 19-9auge needle. In either instance the catheter is advanced under fluoroscopic guidance into the ascending aorta and then through the aortic valve into the left ventricle. Because of the difficulty encountered in passing a catheter in a retrograde manner through the aortic valves, this method is not without hazard. It is usually successful only when a marked degree of aortic insufficiency is present. INDICATIONS AND CONTRAINDICATIONS
It is difficult to define clearly the indications and contraindications for cardiac catheterization because in each patient the small inherent
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risk of the procedure must be weighed against the importance of the data which are sought. In general, cardiac catheterization is of most value as an aid in the identification of congenital and acquired lesions which have not been delineated previously by simpler diagnostic methods. In addition, the study will yield data as to the functional severity of a disease process. This information may play an important role in determining treatment. Cardiac catheterization has also been used to investigate functional changes occurring in other diseases and those resulting from the use of drugs or surgery. There are only two well established cardiac contraindications to cardiac catheterization: recent myocardial infarction and paroxysmal ventricular tachycardia. The presence of subacute bacterial endocarditis, active rheumatic fever and pulmonary embolism may be considered relative contraindications. Under most circumstances it is wise to delay catheterization until the active process has become quiescent. Severely ill and excitable patients tolerate the procedure poorly. Data obtained under these circumstances may be difficult to interpret correctly. COMPLICATIONS
The most common and potentially most hazardous complication of cardiac catheterization is the development of an arrhythmia during the procedure. It is the experience of this Clinic as well as of others l5 • 16. 17 that it is unusual to perform catheterization of the right side of the heart without the development of some ectopic beats. These arrhythmias usually result from stimulation of the endocardial wall by the catheter tip during its passage through the heart or at the time when blood is withdrawn from the cardiac chambers. Occasionally, ectopic disturbances may be seen when the catheter tip is still in the venous system and has not entered the heart. Many types of arrhythmia have occurred, including atrial, nodal and ventricular extrasystoles, atrial tachycardia, flutter and fibrillation, right bundle branch block, varying degrees of atrioventricular block, ventricular tachycardia and ventricular fibrillation. The most important single factor in the prevention of serious rhythm disturbances is continuous electrocardiographic control during the procedure. The onset of any disturbance is then quickly appreciated and usually will subside when the catheter is moved. In some laboratories, premedication of the patient with quinidine or procaine amide is practiced routinely,t~ but in the majority of laboratories this is not done. During some 250 catheterizations carried out in this Hospital ventricular fibrillation occurred in 2 patients. In both instances thoracotomy was performed and cardiac massage instituted. After the application of repeated electric shocks to the heart an effective cardiac rhythm was restored, and both patients recovered completely. In one of the patients a patent ductus arteriosus was successfully ligated at a later date. Two
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other serious arrhythmias have been noted in this group of patients. A nodal tachycardia persisted for twelve hours in a thirteen year old girl before subsiding spontaneously. The patient was subsequently catheterized without difficulty. Ventricular tachycardia associated with unconsciousness, shock and marked cyanosis occurred in a fourteen year old boy suspected of having Ebstein's malformation. The tachycardia changed spontaneously to atrial fibrillation after one minute with a return of consciousness and the disappearance of cyanosis and shock. Three minutes later the rhythm reverted to normal. Though evidence of myocardial trauma has been demonstrated clearly in dogs after catheterization of the right side of the heart,19 there are only six well documented reports20 , 21, 22, 23, 27 of its occurrence in man. Persistence of a right bundle branch block initiated during catheterization is probably further evidence of myocardial trauma occurring in man. In this Hospital transient right bundle branch block developed in 2 patients when the tip of the catheter was in the outflow tract of the right ventricle. In one instance the conduction defect pen-listed for fifteen minutes after removal of the catheter and in another instance for several hours. Others17 , 23 have noted the persistence of thiR type of arrhythmia for longer periods. Other serious complications have been reported. TheRe inelude transient neurologic episodes resulting from embolization of air24 or small fibrin particles and pulmonary infarction25 following wedging of the catheter in a small pulmonary vessel. These have not been observed in our group of patients. Local irritation and thrombophlebitis at the entrance site of the catheter occur with moderate frequency. The severity of the reaction bears a direct relation to the amount of manipulation of the catheter during the study. The thrombophlebitis may sometimes involve the axillary vein. No reports of pulmonary emboli resulting from this complication have been found. The occurrence of venospasm during the procedure may be troublesome to the patient as well as to the physician. The adequate infiltration of procaine into the area surrounding the site of catheter insertion and the general comfort of the patient are important factors in its control. Occasionally syncopal episodes accompanied by pallor, sweating and bradycardia may develop. They are usually controlled by the simple supportive measures. Formerly, pyrogenic reactions occurred with moderate frequency. Today this complication is rarely seen, owing to better techniques for the care and sterilization of the catheters. Catheterization of the left side of the heart either by direct pUllcture of the left atrium or in a retrograde manner from a peripheral artery is not yet widely practiced. It is subject to many of the complications associated with venous catheterization, as well as the possibility of intrathoracic hemorrhage, when the left atrium is punctured directly. Though
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no serious complications have been reported in the small series in which the left atrium was directly punctured, two fatalities occurred as a result of retrograde catheterization of the left ventricle from the aorta. 14 In this Clinic the left ventricle has been catheterized in 3 patients by the insertion of a small polyvinyl catheter into the femoral artery through a 19-9auge needle. Two patients had marked aortic insufficiency, while the third patient had an apparently normal aortic valve. Utilizing the small-catheter technique,26 200 retrograde arterial catheterizations have been done in this Hospital through the brachial or femoral artery. Except for the three instances just mentioned, the catheter was advanced no further than the aortic valve. Two instances of transient occlusion and one of thrombosis of the brachial artery complicated these procedures. In each case puncture of the brachial artery had been accomplished with difficulty. In some patients, after insertion of the catheter into the brachial artery, small painful areas developed in the distal parts of the fingers six to eight hours later. These symptoms disappeared in several days without sequelae. Because no local arterial complications other than small hematomas were noted when the femoral artery was used for arterial catheterization, it is now customary to do these studies at this site rather than in the arm. Despite the potential hazards of cardiac catheterization the number of deaths has been small. A recent study 27 of a committee of the American Heart Association showed four deaths in 5691 patients SUbjected to right-sided heart catheterizations performed in eight institutions. Although left-sided heart catheterization is still only rarely done, it would appear that it may be a somewhat more hazardous procedure than venous catheterization. lJSE OF CARDIAC CATHETERIZATION IN CONGENITAL HEAHT DISEASE
In the evaluation of patients with congenital heart disease a careful history, a physical examination, fluoroscopy of the heart and lungs and electrocardiography will often disclose two groups of patients who need no further study. One of these groups consists of those who are not limited physically by their disease, who show little evidence of cardiovascular strain and in whom surgical correction of the suspected congenital lesion is associated with considerable risk. These patients should be followed up closely until some change in their status occurs or until, as a result of newer techniques, the risk of surgical intervention is markedly decreased. At that time further efforts should be made to arrive at an exact diagnosis. The other group of patients consists of those in whom a diagnosis can be made with a high degree of certainty on clinical grounds alone. This group includes those with a continuous murmur of maximum intensity
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in the second left intercostal space, a widened pulse pressure and increased vascularity of the lungs, these findings being diagnostic of patent ductus arteriosus. Rarely these signs may be caused by a communication between the root of the aorta and the pulmonary artery or by the combination of aortic insufficiency and a ventricular septal defect,28. 29. 30 but the relative rarity of patients with such lesions as well as the problems involved in differentiating them from a patent ductus justifies thoracotomy on the clinical findings alone. Also included in this group are those patients with coarctation of the aorta, the majority of whom may be operated upon without special studies. Occasionally, angiocardiography may be of aid to the surgeon in these patients by delineating the size and position of the coarcted area. Lastly, an occasional patient with the tetralogy of Fallot may be operated upon on the basis of the clinical findings alone when the risk involved in further studies is considered to be high. In all other patients with congenital heart disease further studies should be undertaken in an effort to arrive at an exact physiologic and anatomic diagnosis. These studies are accomplished by the techniques of cardiac catheterization and angiocardiography. Patients with acyanotic heart disease are best studied first by cardiac catheterization. In some instances, however, catheterization may fail to lead to a definitive diagnosis, and angiocardiography is subsequently performed. The diagnosis of patients with cyanotic heart disease is usually best accomplished by angiocardiography. When this technique fails to define the defect, cardiac catheterization is done. Defects Associated with a Rise in Oxygen Content in the Great Veins and the Right Atrimn
The blood entering the right atrium normally comes from three sources, the two venae cavae and the coronary sinus. Since each source contains blood from a different segment of the body, each may have a different oxygen content. Mixing within the right atrium is not complete. Atrial blood samples may consist predominantly of blood derived from one of these sources rather than a mixture of all of them. A low value for atrial oxygen content may be obtained if the catheter tip is near the ostium of the coronary sinus; a high value may be found when the sample is drawn from a point close to the orifice of the inferior vena cava. In the first instance the presence of an arteriovenous shunt might be masked; in the second case the presence of such a shunt might be falsely suspected. When the atrial oxygen content is much higher than that of the venae cavae, a shunt must exist. However, when the difference in oxygen content is less than 1.9 volumes per cent between these two sites, the interpretation of the data is open to question. Indeed, it is often
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necessary to direct the catheter into the defect itself to demonstrate conclusively that such an anomaly exists. In the group of patients studied in this Hospital four types of congenital defects were associated with the finding of significant oxygen differences between the superior vena cava, inferior vena cava and right atrium: (1) atrioseptal defect, (2) anomalous drainage of a pulmonary vein into the vena cava or right atrium, (3) a communication between the sinus of Valsalva and right atrium, (4) a communication between the aorta and right atrium through an anomalous coronary artery.
Fig. 182. Roentgenogram showing a catheter which has been passed from the right atrium into an anomalous pulmonary vein. The catheter tip lies well beyond the heart shadow in the right lung field.
In the last two types of defects the clinical finding of a continuous murmur and the demonstration of the entry of oxygenated blood into the right atrium by catheterization led to a correct diagnosis of an aortico-atrial communication and differentiated these patients from those with the first two types of congenital abnormalities. The differentiation between the anomalous drainage of a pulmonary vein and an atrioseptal defect may prove extremely difficult. In part this difficulty is due to the occurrence in some patients of the two defects simultaneously. When the catheter passes directly into the lung field from either the great veins or the right auricle, as seen in Figure 182, and fully oxygenated blood is sampled from this site, the diagnosis of an anomalous connection of a pulmonary vein may be made with certainty. When, however, the catheter passes from right to left through the body of the heart into a pulmonary vein, it is difficult to decide whether the catheter has entered the pulmonary vein directly from the
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right atrium or only after passing into the left atrium through an atrioseptal defect. This type of abnormality may sometimes be more clearly defined by taking multiple blood samples during withdrawal of the catheter with the patient obliquely positioned under the fluoroscope. Further definition of these anomalies has been obtained by recording dye dilution curves with the blood cuvette oximeter after injection of Evans blue dye into both pulmonary arteries. 31 By this technique it is possible in some patients to localize anomalous pulmonary venous drainage to one lung. The determination of intracardiac pressures has been of little value in the diagnosis of shunts entering the great veins and right atrium. No unusual findings were noted in the atrial pressure curves recorded in our 3 patients with communications between the aorta and right atrium. On the other hand, the height of the pulmonary arterial pressure, the calculation of pulmonary resistance and the size and direction of the shunt are important factors in determining the advisability of operation. The degree of pulmonary resistance and the pulmonary arterial pressure are related both to the size of the shunt and its duration. It is more common to find normal or only slightly elevated pulmonary arterial pressure in the face of large left-to-right shunts in children than in adults. As age advances and pulmonary resistance increases, patients with atrioseptal defects show increasing evidence of significant right-toleft shunts. Defects Associated with a Rise in Oxygen Content in the Right Ventricle
The mixing of venous blood is more complete in the right ventricle than in the right atrium. An increase of 0.9 volume per cent of ventricular oxygen content over the atrial oxygen content is considered significant of the admixture of arterial blood with venous blood in the right ventricular cavity. Three types of congenital defects are associated with a significant rise in oxygen content in the right ventricle, as compared to that of the right atrium: (1) ventricular septal defect, (2) communication between the aorta and pulmonary artery with pUlmonic insufficiency, (3) communication between the sinus of Valsalva and the right ventricle. The last two types of abnormalities are usually associated with a continuous murmur which differentiates them from simple ventricular septal defects, but the identification of one from the other may be extremely difficult. In general, in those patients with a patent ductus arteriosus and pulmonic insufficiency a rise in oxygen content found just beneath the pulmonary valve will be associated with a further rise in the pulmonary artery, while no such secondary rise will be found in patients with a communication from the aorta to the ventricle through the sinus of Valsalva. In addition, the presence of pulmonic insufficiency
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may be suspected when the diastolic pressure in the pulmonary artery is low and tends to approximate that of the end diastolic pressure in the right ventricle. Recently a patient was studied in this hospital who had a continuous murmur. Venous catheterizations done five years previously and two months prior to death showed a large shunt of blood high in the right ventricle with pulmonic insufficiency, the diastolic pressure in the pulmonary artery equaling that of the end diastolic pressure in the right ventricle. These findings did not clearly differentiate between a patent
Fig. 183. Simultaneous electrocardiogram (retouched) and pressure record obtained during retrograde catheterization of the aorta in a patient with an aneurysm of the sinus of Valsalva which had ruptured into the right ventricle. The catheter passed from the root of the aorta directly into the right ventricle. The marked change in pressure and contour of the curves is noted as the catheter is withdrawn from the right ventricle into the aorta. The diagnosis was confirmed at necropsy.
ductus arteriosus with pulmonic insufficiency and a ruptured aneurysm of the sinus of Valsalva entering the right ventricle. During retrograde arterial catheterization a small polyvinyl catheter was passed directly from the root of the aorta into the right ventricle. The pressure changes obtained are shown in Figure 183. Subsequently, necropsy confirmed the diagnosis of an aneurysm of the sinus of Valsalva which had ruptured into the right ventricle. The height of the right ventricular and pulmonary arterial pressures may be of some aid in the differentiation of ventricular septal defects from atrioseptal defects in young patients. Children with ventricular septal defects tend to have moderate to marked pressure elevations at these two sites in comparison to the usually normal or slightly elevated pressures occurring with atrioseptal defects.
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Defects Associated with a Rise in Oxygen Content in the Pul1l1Onary Artery
Within the pulmonary artery venous blood is well mixed, so that a rise of 0.5 volume per cent in the oxygen content of pulmonary arterial blood over that of the right ventricle is considered significant of the admixture of venous and arterial blood at this site. Four types of defects may produce a significant increase in the oxygen content of the pulmonary arterial blood. (1) patent ductus arteriosus, (2) a communication between the root of the aorta and the pulmonary artery, (3) ventricular septal defect, (4) overriding of the pulmonary artery. A significant increase in the oxygenation of pulmonary arterial blood in patients with ventricular septal defects is sometimes found when, for technical reasons, it is impossible to sample blood in the outflow tract of the right ventricle. Under these circumstances comparison of specimens taken low in the right ventricle and in the pulmonary artery will often show a rise in the pulmonary arterial oxygen content. Patients with simple ventricular septal defects as well as those with overriding of the pulmonary artery can usually be differentiated from those with aorticopulmonary communications by the absence of a continuous murmur in the former types of patients. In patients with aorticopulmonary communications the continuous murmur, however, may not be present when the pulmonary arterial pressure approaches, equals or is greater than the aortic pressure. Under these circumstances the direction of the flow in the defect tends to be reversed. The diagnosis of these types of anomalies is often extremely difficult and at times can be accomplished only by passage of the catheter through the defect. An additional clue to the presence of patent ductus with reversal of flow may be provided by the detection of a lower oxygen content in the arterial blood of the leg as compared with that of the arm.32 As stated previously, catheterization is not usually performed in patients with classical signs of a patent ductus arteriosus. When doubt exists as to the continuous nature of the murmur or when any other unusual findings are present, catheterization should be carried out in HIl effort to arrive at a correct diagnosis. Pulmonary Stenosis
The diagnosis of pulmonary stenosis is established by finding a marked elevation of right ventricular RVRt.olic pressure over that of the pulmonary artery during venous catheterization. The type of stenosis (valvular [Fig. 184], infundibular [Fig. 185], or a combination of both [Fig. 186]) may be determined by continuously recording pulse pressure curves during the slow withdrawal of the catheter from the pulmonary artery through the pulmonary valve and right ventricle. Two patients
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studied in this Hospital showed evidence of pulmonary stenosis, though no actual valvular or infundibular changes of a congenital origin were present. In the one instance a tumor of the right ventricular wall ob-
··-150-· '·-50Fig. 184. Simultaneous electrocardiogram and pressure record obtained in a patient with valvular pulmonary stenosis. The marked change in pressure is noted as the catheter is withdrawn from the pulmonary artery into the right ventricle. Pressure in millimeters of mercury is shown on the left.
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Fig. 185. Simultaneous electrocardiogram and pressure record obtained in a patient with infundibular stenosis. The upper record shows the change in the configuration of the pressure curve without any change in systolic pressure as the catheter is withdrawn from the pulmonary artery into the infundibular pouch. The lower record shows the marked change in systolic pressure as the catheter is withdrawn from the infundibular pouch into the lower portion of the right ventricle. The patient had an associated ventricular septal defect with a large shunt from left to right. No peripheral unsaturation was present.
structed the flow of blood into the pulmonary artery. In the other case a sinus of Valsalva aneurysm protruding into the right ventricular cavity was the cause of the decreased pulmonary arterial pressure. Minor differences between the systolic pressure in the pulmonary artery and right ventricle are occasionally seen. Whether these changes are due to
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not a mild degree of anatom ic stenosis or a relative type of stenosis is clear. Cathet erizatio n findings in patient s with pulmon ary stenosis are imuniportan t in determining the advisab ility of operation. Althou gh no s stenosi of form criteria have been established as to the degree to al Hospit this in warran ting surgical interve ntion, it is custom ary e operate upon those patient s in whom the pulmon ary arterial pressur of mm. 80 above e is normal or low and the right ventric ular pressur r, mercury. Surgical correction of the pulmon ary stenosis alone, howeve right left-toa with is of questionable value when the defect is associated e of shunt throug h an associated septal defect and there is no evidenc 33 periphe ral arteria l unsatu ration at rest.
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obtaine d in a Fig. 186. Simulta neous electroc ardiogra m and pressure record in preschanges The . stenosis ary pulmon ular infundib and r valvula oatient with through artery ary pulmon the from wn withdra is r sure are noted as the cathete the right ventricl e. Pressur e in millime ters of mercury is on the left.
Cyano tic Conge nital Heart Diseas e
is The diagnosis in patient s with cyanotic congenital heart disease howes, instanc some In most readily obtaine d by angiocardiography. of ever, the presence or absence of pulmon ary stenosis or the exact site such In alone. ue the shunt cannot be clearly defined by this techniq the patient s venous cathete rization may be of materia l aid in clarifying situatio n. to Althou gh the shunt in these patient s is predom inantly from right s ination determ e left, it is usually bidirectional. For this reason multipl will heart the of side of oxygen conten t in the chambers of the right the often disclose the position of the defect. In additio n, passage of . location its to as cathete r throug h the defect leaves little question of The differentiation of Eisenmenger's complex from the tetralo gy ary pulmon the of n Fallot is at times extremely difficult. Cathet erizatio the artery, when successful, will establish the diagnosis by determining also has n erizatio presence or absence of pulmon ary stenosis. Cathet conbeen of value in the diagnosis of Ebstein 's malformation. In this other each imate dition the right atrial and ventric ular pressures approx closely.34 In cyanotic patient s with pulmon ary stenosis, determ ination of the
Cardiac Catheterization in Heart Disease
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exact nature of the stenosis as well as the type of associated defect is important in the choice of the surgical procedure to be used. When the congenital abnormality is the tetralogy of Fallot, the Blalock-Taussig operation has produced good results. When pulmonary stenosis and atrioseptal defect coexist in a cyanotic patient, this procedure may be followed by right-sided heart failure. In these patients, therefore, pulmonary valvulotomy is the operation of choice.3 • USE OF CARDIAC CATHETERIZATION IN ACQUIRED HEART DISEASE
Cardiac catheterization has been of unquestioned value in the study of patients with acquired heart disease. Its value as a diagnostic tool in these patients is not yet so clearly established. This is partly because it is difficult to interpret pressure curves in regard to their hemodynamic significance. That these relations are not as simple as previously thought has been shown by Peterson. 36 Rheulllatic Valvular Heart Disease
Venous catheterization has been widely used in evaluating the functional status of the mitral valve in patients with rheumatic heart disease. Its use for this purpose is dependent on the recording of tracings truly indicative of the pressure variations occurring in the left atrium and pulmonary veins either by direct puncture of the atrium or through a venous catheter wedged in the small pulmonary vessel. Although one group of investigators found a close similarity between wedge pressures and left atrial pressures measured simultaneously at operation,37 not all investigators are agreed on the similarity of pressures measured at these two sites. 3s The normal mean value for wedge pressure lies between 6 and 12 mm. of mercury. In patients with mitral stenosis of a significant degree this value is usually elevated. When a normal value is obtained at rest in the presence of mitral stenosis, moderate amounts of exercise will be associated with an elevation of the wedge pressure. In patients with mitral insufficiency of a major degree a prominent systolic rise in pressure is usually seen in the left atrial and pulmonary wedge recordings,1° as demonstrated in Figure 187. In some instances the presence of an insufficiency wave in tracings of wedge pressures has not been associated with the discovery of a major degree of mitral insufficiency at operation, while in other cases a large systolic . rise in the wedge pressure has been seen when mitral stenosis was thought by the surgeon to be the predominant lesion.'-This lack of correlation 'between the operative and catheterization findings, in some cases, may ~ have a physiologic basis. , It has been stated earlier that large shunts of blood from the aorta 'into the right atrium may be associated with little or no rise in systolic ratrial pressure. On the other hand, when tricuspid insufficiency exists
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with marked distent ion of the right atrium , the typical type of regurgi injectant curve may be recorded, as seen in Figure 188. Similarly, the retion of blood into the left atrium from the left ventricle in mitral The rise. gurgita tion might or might not result in a systolic pressure
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pressure , Fig. 187. Simulta neous recordin g of an electroc ardiogra m, wedge stenosis and premitral with patient a in sounds heart and pressure aortic central systole is clearly dominan t mitral insufficiency. The marked rise in pressure during ency was presinsuffici mitral of degree marked A . seen in recorded wedge pressure ent at operatio n.
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in the Fig. 188. Simulta neous electroc ardiogra m and pressure tracing recordedand triency inferior vena cava in a patient with mitral stenosis , mitral insuffici pressure s obcuspid insufficiency. The pressure curve is much similar to wedge of mercury ; mm. 30 , pressure Systolic ency. insuffici tained in patients with mitral diastolic pressure , 10 mm. of mercury .
fact explanation for these appare nt discrepancies probab ly lies in the befactors other of result the ly probab is rise that the atrial pressure of One n. injectio of e pressur the and d injecte sides the volume of blood the Despite r. chambe atrial the of ibility these factors is the distens ce obvious complexities involved in relating pressure, flow and resistan possibeen has it , system ascular cardiov the of in'the various segments the ble in many instances to estimat e roughly the cross-sectional area of
Cardiac Catheterization in Heart Disease
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mitral and other valvular orifices from the data derived during cardiac catheterization. 39
EKG
Fig. 189. Simultaneous electrocardiogram and right atrial pressure recorded in a patient with constrictive pericarditis. The elevation of pressure and the Mshaped configuration of the curves with the early diastolic dip is seen. The electrocardiogram has been retraced.
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Fig. 190. Right ventricular pressure curves obtained in the same patient as in Figure 20. The elevated end diastolic pressure, the small pulse pressure and the early diastolic dip can be seen. Comparison with Figure 14 shows a marked similarity in the configuration of the right ventricular pressure curves. At operation a markedly thickened and calcified pericardium was found. The electrocardiogram has been retraced.
Constrictive Pericarditis
Right atrial and right ventricular pulse pressure curves of the type seen in Figures 189 and 190 are often found in patients with constrictive pericarditis. The small right ventricular pulse pressure, the high lend diastolic pressure, the early diastolic dip and the M-shaped con-
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figuration of the atrial curves have been thought diagnostic of this condition. 40 A comparison of Figure 190 with Figure 183 shows that these types of pressure curves may exist in conditions other than constrictive pericarditis when right ventricular failure is presentY· 42 While the finding of such curves is not diagnostic of constrictive pericarditis, their absence is strong evidence against the presence of a significant degree of cardiac compression. Right-Sided Heart Failure Due to Chronic Puhnonary Disease
The diagnosis of chronic lung disease as a cause of right-sided heart failure is at times difficult to establish. In such cases cardiac catheterization is of aid by ruling out the presence of intracardiac shunts, by demonstrating marked pulmonary hypertension with normal wedge pressures and by showing decreased oxygenation of a blood sample obtained when the catheter is wedged in a small pulmonary vessel. USE OF CARDIAC CATHETERIZATION IN MISCELLANEOUS CONDITIONS
By permitting a functional evaluation of the cardiovascular status catheterization has at times contributed to the diagnosis of Paget's disease of the bone, beriberi heart disease, thyrotoxicosis and peripheral arteriovenous fistula, each of these conditions being associated with an increased cardiac output. In addition, in this Hospital venous catheterization has been useful in excluding some of the causes of heart failure in patients with impaired cardiovascular function for unknown reasons. CONCLUSION
1. Cardiac catheterization as a diagnostic and research technique is now well established in most large institutions. 2. When performed by a group of physicians experienced in its use, cardiac catheterization is accompanied by minimal risk to the patient. 3. The indications for its use as well as its value in the study of congenital and acquired heart disease have been stated. 4. When utilized for diagnosis, the data obtained by this technique must be evaluated in the light of the information obtained by all other diagnostic methods. REFERENCES 1. Forssman, W.: Die Sondierung des rechten Herzens. Klin. Wchnschr., 8: 2085,
1929. 2. Peterson, L. H., Dripps, R. D., and Risman, G. C.: A Method for Recording the Arterial Pressure Pulse and Blood Pressure in Man. Am. Heart J., 37: 771, 1949. 3. Lambert, E. H., and Jones, R. E.: The Characteristics of a Resistance Wire Manometer for Measuring Blood Pressure in Cardiac Catheterization Studies. Proc. Staff Meet., Mayo Clin., 23: 487, 1948.
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4. Van Slyke, D. D., and Neill, J. M.: The Determination of Gases in Blood and Other Solutions by Vacuum Extraction and Manometric Measurement. J. BioI. Chem., 61: 523,1924. 5. Groom, D., Wood, E. H., Burchell, H. B., and Parker, R. L.: The Application of an Oximeter for Whole Blood to Diagnostic Cardiac Catheterization. Proc. Staff Meet., Mayo Clin., 23: 601, 1948. 6. Swan, H. J. C., and Wood, E. H.: Localization of Cardiac Defects by Dye Dilution Curves Recorded after Injection of T-1824 at Multiple Sites in the Heart and Great Vessels during Cardiac Catheterization. Proc. Staff Meet., Mayo Clin., 23: 601, 1948. 7. Nicholsen, J. W., Ill, Burchell, H. B., and Wood, E. H.: A Method for the Continuous Recording of Evans Blue Dye Curves in Arterial Blood and Its Application to the Diagnosis of Cardiovascular Abnormalities. J. Lab. & Clin. Med., 37: 353, 1951. 8. Ziegler, R.: Circulation Time Determinations from the Right Ventricle. Circulation 4: !l05, 1951. 9. Hellems, H. K., Haynes, F. W., Dexter, L., and Kinney, T. D.: Pulmonary Capillary Pressures in Animals Estimated by Venous and Arterial Catheterization. Am. J. Physiol., 155: 98,1948. 10. LangerlOf, H., and Werko, L.: Studies on the Circulation of the Blood in Man. VI. The Pulmonary Capillary Venous Pulse in Man. Scandinav. J. Clin. & Lab. Invest., 1: 147, 1949. 11. Allison, P. R., and Linden, R. J.: The Bronchoscopic Measurement of Left Auricular Pressure. Circulation, 7: 669, 1953. 12. Fisher, D. L., Childs, T. B., Ford, W. B., and Kent, E. M.: Left Atrium Pressure Pulse Curves in Mitral Valve Disease. Abst. Am. Heart A. Meet., April, 1954. 13. Blakemore, W.: Personal communication. 14. Zimmerman, H. A., Scott, R. W., and Becker, N. 0.: Catheterization of the Left Side of the Heart. Circulation, 1: 357, 1950. 15. Goldman, I. R., Blount, S. G., Jr., Friedlich, A. L., and Bing, R. J.: Electrocardiographic Observations during Cardiac Catheterization. Bull. Johns Hopkins Hosp., 86: 141, 1950. 16. Ravin, A., DressIer, S., Bronfin, G., and Hnrst, A.: Cardiac Arrhythmias Produced during Right Heart Catheterization: Report of Two Cases of Transient Partial Right Bundle Branch Block. Ann. Int. Med., 33: 174, 1950. 17. Fowler, N. 0.: Cardiac Catheterization in the Diagnosis of Adult Heart Disease. Ann. Int. Med., 38: 478, 1953. 18. Zinn, W. J., and others: The Use of Oral Quinidine and Procaine Amide as Premedications for Cardiac Catheterization. Am. Heart J., 43: 451, 1952. 19. Ellis, E. J., Essex, H. E., and Edwards, .f. E.: Lesions of the Heart in Do!!;s Following Cardiac Catheterization. Pl'Oc. Staff Meet., Mayo Clin., 25: 73, 1950. 20. Edwards, J. E., Helmholz, F. H., DuShane, J. W., and Burchell, H. B.: Patho logic Study of Hearts Previously Catheterized. Proc. Staff Meet., Mayo Clin., 28: 113, 1953. 21. Johnson, A. L., Woolin, D. G., and Ross, J. B.: Heart Catheterization in the Investigation of Congenital Heart Disease. Canad. M.A.J., 56: 249,1947. 22. Holling, H. E., and Zak, G. A.: Cardiac Catheterization in the Investigation of Congenital Heart Disease. Brit. Heart J., 12: 153, 1950. 23. Sancetta, S. M., Hachel, D. B., and Lynn, R. B.: Subendocardial Trauma Produced by Right Sided Catheterization of the Heart in Man. Am. Heart J., 45: 491, 1953. 24. Zimdahl, W. T.: Disorders of the Cardiovascular System Occurring with Catheterization of the Right Side of the Heart. Am. Heart J., 41: 204, 1951. 25. Houssay, H. E. J., Haynes, F. W., and Dextcr, L.: Pulmonary Infarction from Catheterization. Pl'Oc. Soc. Expel'. BioI. & Med., 79: 444, 1952. 26. Schnabel, T. G., Jr., and others: A Technique of Vascular Catheterization with Small Plastic Catheters: Its Utilization to Measure the Arterial Pulse Wave Velocity in Man. Circulation, 5: 257, 1952.
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27. Cournand, A., and others: Report of the Committee on Cardiac Catheterization and Angiocardiography of the American Heart Association. Circulation 7: 769, 1953. 28. Hurst, W. W., and Schemm, F. R.: High Ventricular Septal Defect with Slight Dextro-position of the Aorta (Eisenmenger Type) Which Presented the Clinical Features of Patent Ductus Arteriosus. Am. Heart J., 36: 144, 1948. 29. Ash, R., and Murphy, L.: High Ventricular Septal Defect and Slight Dextroposition of the Aorta (Eisenmenger Complex) Associated with Deformed Aortic Valve Stimulating Patent Ductus Arteriosus. J. Pediat. 37: 249, 1950. 30. Morgan, E. H., and Burchell, H. B.: Ventricular Septal Defect Simulating Patent Ductus Arteriosus. Proc. Staff Meet., Mayo Clin., 25: 69,1950. 31. Swan, H. J. C., Burchell, H. B., and Wood, E. H.: Differential Diagnosis at Cardiac Catheterization of Anomalous Pulmonary Venous Drainage Related to Atrial Septal Defects or Abnormal Venous Connections. Proc. Staff Meet., Mayo Clin., 28: 452, 1953. 32. Huitgren, H., Selzer, A., Purdy, A., Holman, E., and Gerbode, A.: The Syndrome of Patent Ductus Arteriosus with Pulmonary Hypertension. Circulation, 8: 15, 1953. 33. Moffitt, G. R., Jr., Zinsser, H. F., Ruo, P. T., Johnson, J., and Schnabel, T. G., Jr.,: Pulmonary Stenosis with Left to Right Intracardiac Shunts. Am. J. Med., 26: 521, 1954. 34. Broadbent, J. C., Wood, E. H., Burchell, H. B., and Parker, R. L.: Ebstein's Malformation of the Tricuspid Valve: Report of Three Cases. Proc. Staff Meet., Mayo Clin., 28: 27,1953. 35. Engle, M. A., and Taussig, H. B.: Valvular Pulmonic Stenosis with Intact Ventricular Septum and Patent Foramen Ovale. Report of Illustrative Cases and Analyses of Clinical Syndrome. Circulation, 2: 481, 1950. 36. Peterson, L. H.: The Dynamics of Pulsatile Flow. Circulation Research, 2: 127, 1954. 37. Connolly, D. C., Tompkins, R. G., Leo, R., Rirklin, J. W., and Wood, E. H.: Pulmonary Artery Wedge Pressures in Mitral Valve Disease: Relation· ship to Left Atrial Pressures. Proc. Staff Meet., Mayo Clin., 28: 72, 1953. 38. Ankeney, J. L.: Further Experimental Evidence That Pulmonary Capillary Pressures Do not Reflect Cyclic Changes in Left Atrial Pressure. (Mitral Lesions and Pulmonary Embolism). Circulation Research, 1: 58, 1953. 39. Gorlin, R., and Gorlin, S. G.: Hydraulic Formula for Calculation of the Area of the Stenotic Mitral Valve, Cardiac Valves and Central Circulatory Shunts. Am. Heart J., 41: 1, 1951. 40. Yu, P. N. G., Lovejoy, F. W., Jr., Joos, H. A., Nye, R. E., Jr., and Mahoney, E. B.: Right Auricular and Ventricular Pressure Patterns in Constrictive Pericarditis. Circulation, 7: 102, 1953. 41. Hetzel, P. S., Wood, E. H., and Burchell, H. B.: Pressure Pulse in the Right Side of the Heart in a Case of Amyloid Disease and in Case of Idiopathic Heart Failure Simulating Constrictive Pericarditis. Proc. Staff Meet., Mayo Clin., 28: 107, 1953. 42. Wilson, R. H., Borden, C. W., Hoseth, W., Sadoff, C. N., and Dempsey, M. E.: The Pathologic Physiology and Diagnostic Significanee of Pressure Pulses in the Right Heart in Patients with Chronic Constrictive Pericarditis and Pericardial Effusion. Clin. Res. Proc., 2: 9, 1954. 3400 Spruce Street Philadelphia 4, Pa.
HUMAN cardiac catheterization was first performed twenty-five years ago by Forssman,1 using himself as a subject. Although his purpose was to introduce drugs directly into the cardiac chambers, the method has become far more important as a means of acquiring data that had never before been obtained in man. These data have contributed greatly to our understanding of normal and abnormal cardiovascular dynamics. They have led to more accurate diagnosis in both congenital and acquired heart disease and have been of value in the study of many types of cardiac therapy.
TECHNIQUE
Today the technique of catheterization of the right side of the heart is more complex than that which Forssman described in 1929. Radiopaque catheters are inserted through a peripheral vein (usually the basilic vein in the right or left antecubital fossa) after exposure of the vein. When a basilic vein of suitable size cannot be found, the saphenous vein is often used. Local anestheHia is ordinarily used at the site of insertion in adults, but general anesthesia is often required in children and infants. Once the catheter has been inserted into a peripheral vein, it is then directed under fluoroscopic guidance through the great veins, the right atrium, the right ventricle and finally into the pulmonary artery. Pressure measurements may be made and blood samples obtained from any of these sites. Whereas formerly mean pressures were recorded with a saline or mercury manometer, it is customary today to use manometric systems capable of recording accurately the entire pulse pressure curve. 2 , 3 The oxygen content of the blood is usually analyzed From the Robinette Foundation and the Department of Medicine, Hospital of the University of Pennsylvania.
* Assistant Professor of Medicine and Markle Scholar, University of Pennsylvania School of Medicine; Staff Member, Robinette Foundation, Hospital of University of Pennsylvania, Philadelphia. 1617
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Truman G. Schnabel, Jr.
manometrically by the technique of Van Slyke and Neill. 4 In some laboratories oxygen saturations are recorded rapidly by means of the whole blood cuvette oximeter,5 a technique which gives immediate results to the physician performing the study. This method has the added advantage of utilizing small samples of blood for each determination, thus making possible the analysis of many more samples on a patient. Foreign substances such as Evans blue," 7 fluorescein 8 or radiopaque materials may be injected through the catheter into the chambers of the right side of the heart or into the pulmonary artery. Dye dilution curves, circulation times and angiocardiograms obtained in this way are of further aid in the study of many hemodynamic problems. Until recently, direct information concerning the left side of the heart was obtained only when the catheter passed through an intracardiac defect. Because of the importance of acquiring data on the pressure changes occurring within this side of the heart it is now customary during venous catheterization to advance the catheter into a branch of the pulmonary artery until its tip is actually wedged in a small vessel. 9. 10 In this position the small pulmonary vessel becomes an extension of the catheter, so that the recorded pressure is probably fairly representative of the pressure pulse curve occurring in the pulmonary veins and left atrium. Other approaches to the recording of left atrial pressures have recently been demonstrated. These methods involve puncture of the left atrium directly with a small needle. In one method the needle is inserted through the right main bronchus into the left atrium under bronchoscopic visualization ill in the other technique the needle is introduced posteriorly through the eighth or ninth intercostal space percutaneously into the left atrium. 12 In the latter instance a small plastic catheter may be inserted through the needle into the left atrium and advanced into the left ventricle.l 3 The recording of left ventricular and central aortic pressure pulse curves has also been accomplished by retrograde, arterial catheterization. 14 In this method either a venous or a small plastic catheter may be used. The venous type of catheter is inserted into the arterial bed through an exposed peripheral vessel, whereas the small plastic catheter enters the peripheral artery through a 19-9auge needle. In either instance the catheter is advanced under fluoroscopic guidance into the ascending aorta and then through the aortic valve into the left ventricle. Because of the difficulty encountered in passing a catheter in a retrograde manner through the aortic valves, this method is not without hazard. It is usually successful only when a marked degree of aortic insufficiency is present. INDICATIONS AND CONTRAINDICATIONS
It is difficult to define clearly the indications and contraindications for cardiac catheterization because in each patient the small inherent
Cardiac Catheterization in Heart Disease
1619
risk of the procedure must be weighed against the importance of the data which are sought. In general, cardiac catheterization is of most value as an aid in the identification of congenital and acquired lesions which have not been delineated previously by simpler diagnostic methods. In addition, the study will yield data as to the functional severity of a disease process. This information may play an important role in determining treatment. Cardiac catheterization has also been used to investigate functional changes occurring in other diseases and those resulting from the use of drugs or surgery. There are only two well established cardiac contraindications to cardiac catheterization: recent myocardial infarction and paroxysmal ventricular tachycardia. The presence of subacute bacterial endocarditis, active rheumatic fever and pulmonary embolism may be considered relative contraindications. Under most circumstances it is wise to delay catheterization until the active process has become quiescent. Severely ill and excitable patients tolerate the procedure poorly. Data obtained under these circumstances may be difficult to interpret correctly. COMPLICATIONS
The most common and potentially most hazardous complication of cardiac catheterization is the development of an arrhythmia during the procedure. It is the experience of this Clinic as well as of others l5 • 16. 17 that it is unusual to perform catheterization of the right side of the heart without the development of some ectopic beats. These arrhythmias usually result from stimulation of the endocardial wall by the catheter tip during its passage through the heart or at the time when blood is withdrawn from the cardiac chambers. Occasionally, ectopic disturbances may be seen when the catheter tip is still in the venous system and has not entered the heart. Many types of arrhythmia have occurred, including atrial, nodal and ventricular extrasystoles, atrial tachycardia, flutter and fibrillation, right bundle branch block, varying degrees of atrioventricular block, ventricular tachycardia and ventricular fibrillation. The most important single factor in the prevention of serious rhythm disturbances is continuous electrocardiographic control during the procedure. The onset of any disturbance is then quickly appreciated and usually will subside when the catheter is moved. In some laboratories, premedication of the patient with quinidine or procaine amide is practiced routinely,t~ but in the majority of laboratories this is not done. During some 250 catheterizations carried out in this Hospital ventricular fibrillation occurred in 2 patients. In both instances thoracotomy was performed and cardiac massage instituted. After the application of repeated electric shocks to the heart an effective cardiac rhythm was restored, and both patients recovered completely. In one of the patients a patent ductus arteriosus was successfully ligated at a later date. Two
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Truman G. Schnabel, Jr.
other serious arrhythmias have been noted in this group of patients. A nodal tachycardia persisted for twelve hours in a thirteen year old girl before subsiding spontaneously. The patient was subsequently catheterized without difficulty. Ventricular tachycardia associated with unconsciousness, shock and marked cyanosis occurred in a fourteen year old boy suspected of having Ebstein's malformation. The tachycardia changed spontaneously to atrial fibrillation after one minute with a return of consciousness and the disappearance of cyanosis and shock. Three minutes later the rhythm reverted to normal. Though evidence of myocardial trauma has been demonstrated clearly in dogs after catheterization of the right side of the heart,19 there are only six well documented reports20 , 21, 22, 23, 27 of its occurrence in man. Persistence of a right bundle branch block initiated during catheterization is probably further evidence of myocardial trauma occurring in man. In this Hospital transient right bundle branch block developed in 2 patients when the tip of the catheter was in the outflow tract of the right ventricle. In one instance the conduction defect pen-listed for fifteen minutes after removal of the catheter and in another instance for several hours. Others17 , 23 have noted the persistence of thiR type of arrhythmia for longer periods. Other serious complications have been reported. TheRe inelude transient neurologic episodes resulting from embolization of air24 or small fibrin particles and pulmonary infarction25 following wedging of the catheter in a small pulmonary vessel. These have not been observed in our group of patients. Local irritation and thrombophlebitis at the entrance site of the catheter occur with moderate frequency. The severity of the reaction bears a direct relation to the amount of manipulation of the catheter during the study. The thrombophlebitis may sometimes involve the axillary vein. No reports of pulmonary emboli resulting from this complication have been found. The occurrence of venospasm during the procedure may be troublesome to the patient as well as to the physician. The adequate infiltration of procaine into the area surrounding the site of catheter insertion and the general comfort of the patient are important factors in its control. Occasionally syncopal episodes accompanied by pallor, sweating and bradycardia may develop. They are usually controlled by the simple supportive measures. Formerly, pyrogenic reactions occurred with moderate frequency. Today this complication is rarely seen, owing to better techniques for the care and sterilization of the catheters. Catheterization of the left side of the heart either by direct pUllcture of the left atrium or in a retrograde manner from a peripheral artery is not yet widely practiced. It is subject to many of the complications associated with venous catheterization, as well as the possibility of intrathoracic hemorrhage, when the left atrium is punctured directly. Though
Cardiac Catheterization in Heart Disease
1621
no serious complications have been reported in the small series in which the left atrium was directly punctured, two fatalities occurred as a result of retrograde catheterization of the left ventricle from the aorta. 14 In this Clinic the left ventricle has been catheterized in 3 patients by the insertion of a small polyvinyl catheter into the femoral artery through a 19-9auge needle. Two patients had marked aortic insufficiency, while the third patient had an apparently normal aortic valve. Utilizing the small-catheter technique,26 200 retrograde arterial catheterizations have been done in this Hospital through the brachial or femoral artery. Except for the three instances just mentioned, the catheter was advanced no further than the aortic valve. Two instances of transient occlusion and one of thrombosis of the brachial artery complicated these procedures. In each case puncture of the brachial artery had been accomplished with difficulty. In some patients, after insertion of the catheter into the brachial artery, small painful areas developed in the distal parts of the fingers six to eight hours later. These symptoms disappeared in several days without sequelae. Because no local arterial complications other than small hematomas were noted when the femoral artery was used for arterial catheterization, it is now customary to do these studies at this site rather than in the arm. Despite the potential hazards of cardiac catheterization the number of deaths has been small. A recent study 27 of a committee of the American Heart Association showed four deaths in 5691 patients SUbjected to right-sided heart catheterizations performed in eight institutions. Although left-sided heart catheterization is still only rarely done, it would appear that it may be a somewhat more hazardous procedure than venous catheterization. lJSE OF CARDIAC CATHETERIZATION IN CONGENITAL HEAHT DISEASE
In the evaluation of patients with congenital heart disease a careful history, a physical examination, fluoroscopy of the heart and lungs and electrocardiography will often disclose two groups of patients who need no further study. One of these groups consists of those who are not limited physically by their disease, who show little evidence of cardiovascular strain and in whom surgical correction of the suspected congenital lesion is associated with considerable risk. These patients should be followed up closely until some change in their status occurs or until, as a result of newer techniques, the risk of surgical intervention is markedly decreased. At that time further efforts should be made to arrive at an exact diagnosis. The other group of patients consists of those in whom a diagnosis can be made with a high degree of certainty on clinical grounds alone. This group includes those with a continuous murmur of maximum intensity
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Truman G. Schnabel, Jr.
in the second left intercostal space, a widened pulse pressure and increased vascularity of the lungs, these findings being diagnostic of patent ductus arteriosus. Rarely these signs may be caused by a communication between the root of the aorta and the pulmonary artery or by the combination of aortic insufficiency and a ventricular septal defect,28. 29. 30 but the relative rarity of patients with such lesions as well as the problems involved in differentiating them from a patent ductus justifies thoracotomy on the clinical findings alone. Also included in this group are those patients with coarctation of the aorta, the majority of whom may be operated upon without special studies. Occasionally, angiocardiography may be of aid to the surgeon in these patients by delineating the size and position of the coarcted area. Lastly, an occasional patient with the tetralogy of Fallot may be operated upon on the basis of the clinical findings alone when the risk involved in further studies is considered to be high. In all other patients with congenital heart disease further studies should be undertaken in an effort to arrive at an exact physiologic and anatomic diagnosis. These studies are accomplished by the techniques of cardiac catheterization and angiocardiography. Patients with acyanotic heart disease are best studied first by cardiac catheterization. In some instances, however, catheterization may fail to lead to a definitive diagnosis, and angiocardiography is subsequently performed. The diagnosis of patients with cyanotic heart disease is usually best accomplished by angiocardiography. When this technique fails to define the defect, cardiac catheterization is done. Defects Associated with a Rise in Oxygen Content in the Great Veins and the Right Atrimn
The blood entering the right atrium normally comes from three sources, the two venae cavae and the coronary sinus. Since each source contains blood from a different segment of the body, each may have a different oxygen content. Mixing within the right atrium is not complete. Atrial blood samples may consist predominantly of blood derived from one of these sources rather than a mixture of all of them. A low value for atrial oxygen content may be obtained if the catheter tip is near the ostium of the coronary sinus; a high value may be found when the sample is drawn from a point close to the orifice of the inferior vena cava. In the first instance the presence of an arteriovenous shunt might be masked; in the second case the presence of such a shunt might be falsely suspected. When the atrial oxygen content is much higher than that of the venae cavae, a shunt must exist. However, when the difference in oxygen content is less than 1.9 volumes per cent between these two sites, the interpretation of the data is open to question. Indeed, it is often
Cardiac Catheterization in Heart Disease
1623
necessary to direct the catheter into the defect itself to demonstrate conclusively that such an anomaly exists. In the group of patients studied in this Hospital four types of congenital defects were associated with the finding of significant oxygen differences between the superior vena cava, inferior vena cava and right atrium: (1) atrioseptal defect, (2) anomalous drainage of a pulmonary vein into the vena cava or right atrium, (3) a communication between the sinus of Valsalva and right atrium, (4) a communication between the aorta and right atrium through an anomalous coronary artery.
Fig. 182. Roentgenogram showing a catheter which has been passed from the right atrium into an anomalous pulmonary vein. The catheter tip lies well beyond the heart shadow in the right lung field.
In the last two types of defects the clinical finding of a continuous murmur and the demonstration of the entry of oxygenated blood into the right atrium by catheterization led to a correct diagnosis of an aortico-atrial communication and differentiated these patients from those with the first two types of congenital abnormalities. The differentiation between the anomalous drainage of a pulmonary vein and an atrioseptal defect may prove extremely difficult. In part this difficulty is due to the occurrence in some patients of the two defects simultaneously. When the catheter passes directly into the lung field from either the great veins or the right auricle, as seen in Figure 182, and fully oxygenated blood is sampled from this site, the diagnosis of an anomalous connection of a pulmonary vein may be made with certainty. When, however, the catheter passes from right to left through the body of the heart into a pulmonary vein, it is difficult to decide whether the catheter has entered the pulmonary vein directly from the
1624
Truman G. Schnabel, Jr.
right atrium or only after passing into the left atrium through an atrioseptal defect. This type of abnormality may sometimes be more clearly defined by taking multiple blood samples during withdrawal of the catheter with the patient obliquely positioned under the fluoroscope. Further definition of these anomalies has been obtained by recording dye dilution curves with the blood cuvette oximeter after injection of Evans blue dye into both pulmonary arteries. 31 By this technique it is possible in some patients to localize anomalous pulmonary venous drainage to one lung. The determination of intracardiac pressures has been of little value in the diagnosis of shunts entering the great veins and right atrium. No unusual findings were noted in the atrial pressure curves recorded in our 3 patients with communications between the aorta and right atrium. On the other hand, the height of the pulmonary arterial pressure, the calculation of pulmonary resistance and the size and direction of the shunt are important factors in determining the advisability of operation. The degree of pulmonary resistance and the pulmonary arterial pressure are related both to the size of the shunt and its duration. It is more common to find normal or only slightly elevated pulmonary arterial pressure in the face of large left-to-right shunts in children than in adults. As age advances and pulmonary resistance increases, patients with atrioseptal defects show increasing evidence of significant right-toleft shunts. Defects Associated with a Rise in Oxygen Content in the Right Ventricle
The mixing of venous blood is more complete in the right ventricle than in the right atrium. An increase of 0.9 volume per cent of ventricular oxygen content over the atrial oxygen content is considered significant of the admixture of arterial blood with venous blood in the right ventricular cavity. Three types of congenital defects are associated with a significant rise in oxygen content in the right ventricle, as compared to that of the right atrium: (1) ventricular septal defect, (2) communication between the aorta and pulmonary artery with pUlmonic insufficiency, (3) communication between the sinus of Valsalva and the right ventricle. The last two types of abnormalities are usually associated with a continuous murmur which differentiates them from simple ventricular septal defects, but the identification of one from the other may be extremely difficult. In general, in those patients with a patent ductus arteriosus and pulmonic insufficiency a rise in oxygen content found just beneath the pulmonary valve will be associated with a further rise in the pulmonary artery, while no such secondary rise will be found in patients with a communication from the aorta to the ventricle through the sinus of Valsalva. In addition, the presence of pulmonic insufficiency
Cardiac Catheterization in Heart Disease
1625
may be suspected when the diastolic pressure in the pulmonary artery is low and tends to approximate that of the end diastolic pressure in the right ventricle. Recently a patient was studied in this hospital who had a continuous murmur. Venous catheterizations done five years previously and two months prior to death showed a large shunt of blood high in the right ventricle with pulmonic insufficiency, the diastolic pressure in the pulmonary artery equaling that of the end diastolic pressure in the right ventricle. These findings did not clearly differentiate between a patent
Fig. 183. Simultaneous electrocardiogram (retouched) and pressure record obtained during retrograde catheterization of the aorta in a patient with an aneurysm of the sinus of Valsalva which had ruptured into the right ventricle. The catheter passed from the root of the aorta directly into the right ventricle. The marked change in pressure and contour of the curves is noted as the catheter is withdrawn from the right ventricle into the aorta. The diagnosis was confirmed at necropsy.
ductus arteriosus with pulmonic insufficiency and a ruptured aneurysm of the sinus of Valsalva entering the right ventricle. During retrograde arterial catheterization a small polyvinyl catheter was passed directly from the root of the aorta into the right ventricle. The pressure changes obtained are shown in Figure 183. Subsequently, necropsy confirmed the diagnosis of an aneurysm of the sinus of Valsalva which had ruptured into the right ventricle. The height of the right ventricular and pulmonary arterial pressures may be of some aid in the differentiation of ventricular septal defects from atrioseptal defects in young patients. Children with ventricular septal defects tend to have moderate to marked pressure elevations at these two sites in comparison to the usually normal or slightly elevated pressures occurring with atrioseptal defects.
1626
l'ruman G. Schnabel, Jr.
Defects Associated with a Rise in Oxygen Content in the Pul1l1Onary Artery
Within the pulmonary artery venous blood is well mixed, so that a rise of 0.5 volume per cent in the oxygen content of pulmonary arterial blood over that of the right ventricle is considered significant of the admixture of venous and arterial blood at this site. Four types of defects may produce a significant increase in the oxygen content of the pulmonary arterial blood. (1) patent ductus arteriosus, (2) a communication between the root of the aorta and the pulmonary artery, (3) ventricular septal defect, (4) overriding of the pulmonary artery. A significant increase in the oxygenation of pulmonary arterial blood in patients with ventricular septal defects is sometimes found when, for technical reasons, it is impossible to sample blood in the outflow tract of the right ventricle. Under these circumstances comparison of specimens taken low in the right ventricle and in the pulmonary artery will often show a rise in the pulmonary arterial oxygen content. Patients with simple ventricular septal defects as well as those with overriding of the pulmonary artery can usually be differentiated from those with aorticopulmonary communications by the absence of a continuous murmur in the former types of patients. In patients with aorticopulmonary communications the continuous murmur, however, may not be present when the pulmonary arterial pressure approaches, equals or is greater than the aortic pressure. Under these circumstances the direction of the flow in the defect tends to be reversed. The diagnosis of these types of anomalies is often extremely difficult and at times can be accomplished only by passage of the catheter through the defect. An additional clue to the presence of patent ductus with reversal of flow may be provided by the detection of a lower oxygen content in the arterial blood of the leg as compared with that of the arm.32 As stated previously, catheterization is not usually performed in patients with classical signs of a patent ductus arteriosus. When doubt exists as to the continuous nature of the murmur or when any other unusual findings are present, catheterization should be carried out in HIl effort to arrive at a correct diagnosis. Pulmonary Stenosis
The diagnosis of pulmonary stenosis is established by finding a marked elevation of right ventricular RVRt.olic pressure over that of the pulmonary artery during venous catheterization. The type of stenosis (valvular [Fig. 184], infundibular [Fig. 185], or a combination of both [Fig. 186]) may be determined by continuously recording pulse pressure curves during the slow withdrawal of the catheter from the pulmonary artery through the pulmonary valve and right ventricle. Two patients
Cardiac Catheterization in Heart Disease
1627
studied in this Hospital showed evidence of pulmonary stenosis, though no actual valvular or infundibular changes of a congenital origin were present. In the one instance a tumor of the right ventricular wall ob-
··-150-· '·-50Fig. 184. Simultaneous electrocardiogram and pressure record obtained in a patient with valvular pulmonary stenosis. The marked change in pressure is noted as the catheter is withdrawn from the pulmonary artery into the right ventricle. Pressure in millimeters of mercury is shown on the left.
lOO-
--PA .--I--RV
OUTFLOW--
500-
I
~ ~
~
I
-RV
OUTFLOW-I-- INFLOW--
lOO-
50-
o
Fig. 185. Simultaneous electrocardiogram and pressure record obtained in a patient with infundibular stenosis. The upper record shows the change in the configuration of the pressure curve without any change in systolic pressure as the catheter is withdrawn from the pulmonary artery into the infundibular pouch. The lower record shows the marked change in systolic pressure as the catheter is withdrawn from the infundibular pouch into the lower portion of the right ventricle. The patient had an associated ventricular septal defect with a large shunt from left to right. No peripheral unsaturation was present.
structed the flow of blood into the pulmonary artery. In the other case a sinus of Valsalva aneurysm protruding into the right ventricular cavity was the cause of the decreased pulmonary arterial pressure. Minor differences between the systolic pressure in the pulmonary artery and right ventricle are occasionally seen. Whether these changes are due to
Truman G. Schnabel, Jr.
1628
not a mild degree of anatom ic stenosis or a relative type of stenosis is clear. Cathet erizatio n findings in patient s with pulmon ary stenosis are imuniportan t in determining the advisab ility of operation. Althou gh no s stenosi of form criteria have been established as to the degree to al Hospit this in warran ting surgical interve ntion, it is custom ary e operate upon those patient s in whom the pulmon ary arterial pressur of mm. 80 above e is normal or low and the right ventric ular pressur r, mercury. Surgical correction of the pulmon ary stenosis alone, howeve right left-toa with is of questionable value when the defect is associated e of shunt throug h an associated septal defect and there is no evidenc 33 periphe ral arteria l unsatu ration at rest.
~ ~ EKG L 2
0'2 SEC.
':~~~
obtaine d in a Fig. 186. Simulta neous electroc ardiogra m and pressure record in preschanges The . stenosis ary pulmon ular infundib and r valvula oatient with through artery ary pulmon the from wn withdra is r sure are noted as the cathete the right ventricl e. Pressur e in millime ters of mercury is on the left.
Cyano tic Conge nital Heart Diseas e
is The diagnosis in patient s with cyanotic congenital heart disease howes, instanc some In most readily obtaine d by angiocardiography. of ever, the presence or absence of pulmon ary stenosis or the exact site such In alone. ue the shunt cannot be clearly defined by this techniq the patient s venous cathete rization may be of materia l aid in clarifying situatio n. to Althou gh the shunt in these patient s is predom inantly from right s ination determ e left, it is usually bidirectional. For this reason multipl will heart the of side of oxygen conten t in the chambers of the right the often disclose the position of the defect. In additio n, passage of . location its to as cathete r throug h the defect leaves little question of The differentiation of Eisenmenger's complex from the tetralo gy ary pulmon the of n Fallot is at times extremely difficult. Cathet erizatio the artery, when successful, will establish the diagnosis by determining also has n erizatio presence or absence of pulmon ary stenosis. Cathet conbeen of value in the diagnosis of Ebstein 's malformation. In this other each imate dition the right atrial and ventric ular pressures approx closely.34 In cyanotic patient s with pulmon ary stenosis, determ ination of the
Cardiac Catheterization in Heart Disease
1629
exact nature of the stenosis as well as the type of associated defect is important in the choice of the surgical procedure to be used. When the congenital abnormality is the tetralogy of Fallot, the Blalock-Taussig operation has produced good results. When pulmonary stenosis and atrioseptal defect coexist in a cyanotic patient, this procedure may be followed by right-sided heart failure. In these patients, therefore, pulmonary valvulotomy is the operation of choice.3 • USE OF CARDIAC CATHETERIZATION IN ACQUIRED HEART DISEASE
Cardiac catheterization has been of unquestioned value in the study of patients with acquired heart disease. Its value as a diagnostic tool in these patients is not yet so clearly established. This is partly because it is difficult to interpret pressure curves in regard to their hemodynamic significance. That these relations are not as simple as previously thought has been shown by Peterson. 36 Rheulllatic Valvular Heart Disease
Venous catheterization has been widely used in evaluating the functional status of the mitral valve in patients with rheumatic heart disease. Its use for this purpose is dependent on the recording of tracings truly indicative of the pressure variations occurring in the left atrium and pulmonary veins either by direct puncture of the atrium or through a venous catheter wedged in the small pulmonary vessel. Although one group of investigators found a close similarity between wedge pressures and left atrial pressures measured simultaneously at operation,37 not all investigators are agreed on the similarity of pressures measured at these two sites. 3s The normal mean value for wedge pressure lies between 6 and 12 mm. of mercury. In patients with mitral stenosis of a significant degree this value is usually elevated. When a normal value is obtained at rest in the presence of mitral stenosis, moderate amounts of exercise will be associated with an elevation of the wedge pressure. In patients with mitral insufficiency of a major degree a prominent systolic rise in pressure is usually seen in the left atrial and pulmonary wedge recordings,1° as demonstrated in Figure 187. In some instances the presence of an insufficiency wave in tracings of wedge pressures has not been associated with the discovery of a major degree of mitral insufficiency at operation, while in other cases a large systolic . rise in the wedge pressure has been seen when mitral stenosis was thought by the surgeon to be the predominant lesion.'-This lack of correlation 'between the operative and catheterization findings, in some cases, may ~ have a physiologic basis. , It has been stated earlier that large shunts of blood from the aorta 'into the right atrium may be associated with little or no rise in systolic ratrial pressure. On the other hand, when tricuspid insufficiency exists
Truma n G. Schnabel, Jr.
1630
with marked distent ion of the right atrium , the typical type of regurgi injectant curve may be recorded, as seen in Figure 188. Similarly, the retion of blood into the left atrium from the left ventricle in mitral The rise. gurgita tion might or might not result in a systolic pressure
EKG L':It
IJ
I1 WEDGE PRESSURE 1 "- :; 1...
"
1\, /~ [\1/ 1\
J
'\
t "
NI V
CENTRAL ~ AORTIC I"- ~ .... /1\ 1"-" I\~ ~j \~ ~I/ .... PRESSURE HEART SOUNDS ~!-;
E: .
V
APEX
~
\
't
40 20
o
Mft\.
"'9
pressure , Fig. 187. Simulta neous recordin g of an electroc ardiogra m, wedge stenosis and premitral with patient a in sounds heart and pressure aortic central systole is clearly dominan t mitral insufficiency. The marked rise in pressure during ency was presinsuffici mitral of degree marked A . seen in recorded wedge pressure ent at operatio n.
111111
EkG.
in the Fig. 188. Simulta neous electroc ardiogra m and pressure tracing recordedand triency inferior vena cava in a patient with mitral stenosis , mitral insuffici pressure s obcuspid insufficiency. The pressure curve is much similar to wedge of mercury ; mm. 30 , pressure Systolic ency. insuffici tained in patients with mitral diastolic pressure , 10 mm. of mercury .
fact explanation for these appare nt discrepancies probab ly lies in the befactors other of result the ly probab is rise that the atrial pressure of One n. injectio of e pressur the and d injecte sides the volume of blood the Despite r. chambe atrial the of ibility these factors is the distens ce obvious complexities involved in relating pressure, flow and resistan possibeen has it , system ascular cardiov the of in'the various segments the ble in many instances to estimat e roughly the cross-sectional area of
Cardiac Catheterization in Heart Disease
1631
mitral and other valvular orifices from the data derived during cardiac catheterization. 39
EKG
Fig. 189. Simultaneous electrocardiogram and right atrial pressure recorded in a patient with constrictive pericarditis. The elevation of pressure and the Mshaped configuration of the curves with the early diastolic dip is seen. The electrocardiogram has been retraced.
EKe
Fig. 190. Right ventricular pressure curves obtained in the same patient as in Figure 20. The elevated end diastolic pressure, the small pulse pressure and the early diastolic dip can be seen. Comparison with Figure 14 shows a marked similarity in the configuration of the right ventricular pressure curves. At operation a markedly thickened and calcified pericardium was found. The electrocardiogram has been retraced.
Constrictive Pericarditis
Right atrial and right ventricular pulse pressure curves of the type seen in Figures 189 and 190 are often found in patients with constrictive pericarditis. The small right ventricular pulse pressure, the high lend diastolic pressure, the early diastolic dip and the M-shaped con-
1632
Truman G. Schnabel, Jr.
figuration of the atrial curves have been thought diagnostic of this condition. 40 A comparison of Figure 190 with Figure 183 shows that these types of pressure curves may exist in conditions other than constrictive pericarditis when right ventricular failure is presentY· 42 While the finding of such curves is not diagnostic of constrictive pericarditis, their absence is strong evidence against the presence of a significant degree of cardiac compression. Right-Sided Heart Failure Due to Chronic Puhnonary Disease
The diagnosis of chronic lung disease as a cause of right-sided heart failure is at times difficult to establish. In such cases cardiac catheterization is of aid by ruling out the presence of intracardiac shunts, by demonstrating marked pulmonary hypertension with normal wedge pressures and by showing decreased oxygenation of a blood sample obtained when the catheter is wedged in a small pulmonary vessel. USE OF CARDIAC CATHETERIZATION IN MISCELLANEOUS CONDITIONS
By permitting a functional evaluation of the cardiovascular status catheterization has at times contributed to the diagnosis of Paget's disease of the bone, beriberi heart disease, thyrotoxicosis and peripheral arteriovenous fistula, each of these conditions being associated with an increased cardiac output. In addition, in this Hospital venous catheterization has been useful in excluding some of the causes of heart failure in patients with impaired cardiovascular function for unknown reasons. CONCLUSION
1. Cardiac catheterization as a diagnostic and research technique is now well established in most large institutions. 2. When performed by a group of physicians experienced in its use, cardiac catheterization is accompanied by minimal risk to the patient. 3. The indications for its use as well as its value in the study of congenital and acquired heart disease have been stated. 4. When utilized for diagnosis, the data obtained by this technique must be evaluated in the light of the information obtained by all other diagnostic methods. REFERENCES 1. Forssman, W.: Die Sondierung des rechten Herzens. Klin. Wchnschr., 8: 2085,
1929. 2. Peterson, L. H., Dripps, R. D., and Risman, G. C.: A Method for Recording the Arterial Pressure Pulse and Blood Pressure in Man. Am. Heart J., 37: 771, 1949. 3. Lambert, E. H., and Jones, R. E.: The Characteristics of a Resistance Wire Manometer for Measuring Blood Pressure in Cardiac Catheterization Studies. Proc. Staff Meet., Mayo Clin., 23: 487, 1948.
Cardiac Catheterization in Heart Disease
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4. Van Slyke, D. D., and Neill, J. M.: The Determination of Gases in Blood and Other Solutions by Vacuum Extraction and Manometric Measurement. J. BioI. Chem., 61: 523,1924. 5. Groom, D., Wood, E. H., Burchell, H. B., and Parker, R. L.: The Application of an Oximeter for Whole Blood to Diagnostic Cardiac Catheterization. Proc. Staff Meet., Mayo Clin., 23: 601, 1948. 6. Swan, H. J. C., and Wood, E. H.: Localization of Cardiac Defects by Dye Dilution Curves Recorded after Injection of T-1824 at Multiple Sites in the Heart and Great Vessels during Cardiac Catheterization. Proc. Staff Meet., Mayo Clin., 23: 601, 1948. 7. Nicholsen, J. W., Ill, Burchell, H. B., and Wood, E. H.: A Method for the Continuous Recording of Evans Blue Dye Curves in Arterial Blood and Its Application to the Diagnosis of Cardiovascular Abnormalities. J. Lab. & Clin. Med., 37: 353, 1951. 8. Ziegler, R.: Circulation Time Determinations from the Right Ventricle. Circulation 4: !l05, 1951. 9. Hellems, H. K., Haynes, F. W., Dexter, L., and Kinney, T. D.: Pulmonary Capillary Pressures in Animals Estimated by Venous and Arterial Catheterization. Am. J. Physiol., 155: 98,1948. 10. LangerlOf, H., and Werko, L.: Studies on the Circulation of the Blood in Man. VI. The Pulmonary Capillary Venous Pulse in Man. Scandinav. J. Clin. & Lab. Invest., 1: 147, 1949. 11. Allison, P. R., and Linden, R. J.: The Bronchoscopic Measurement of Left Auricular Pressure. Circulation, 7: 669, 1953. 12. Fisher, D. L., Childs, T. B., Ford, W. B., and Kent, E. M.: Left Atrium Pressure Pulse Curves in Mitral Valve Disease. Abst. Am. Heart A. Meet., April, 1954. 13. Blakemore, W.: Personal communication. 14. Zimmerman, H. A., Scott, R. W., and Becker, N. 0.: Catheterization of the Left Side of the Heart. Circulation, 1: 357, 1950. 15. Goldman, I. R., Blount, S. G., Jr., Friedlich, A. L., and Bing, R. J.: Electrocardiographic Observations during Cardiac Catheterization. Bull. Johns Hopkins Hosp., 86: 141, 1950. 16. Ravin, A., DressIer, S., Bronfin, G., and Hnrst, A.: Cardiac Arrhythmias Produced during Right Heart Catheterization: Report of Two Cases of Transient Partial Right Bundle Branch Block. Ann. Int. Med., 33: 174, 1950. 17. Fowler, N. 0.: Cardiac Catheterization in the Diagnosis of Adult Heart Disease. Ann. Int. Med., 38: 478, 1953. 18. Zinn, W. J., and others: The Use of Oral Quinidine and Procaine Amide as Premedications for Cardiac Catheterization. Am. Heart J., 43: 451, 1952. 19. Ellis, E. J., Essex, H. E., and Edwards, .f. E.: Lesions of the Heart in Do!!;s Following Cardiac Catheterization. Pl'Oc. Staff Meet., Mayo Clin., 25: 73, 1950. 20. Edwards, J. E., Helmholz, F. H., DuShane, J. W., and Burchell, H. B.: Patho logic Study of Hearts Previously Catheterized. Proc. Staff Meet., Mayo Clin., 28: 113, 1953. 21. Johnson, A. L., Woolin, D. G., and Ross, J. B.: Heart Catheterization in the Investigation of Congenital Heart Disease. Canad. M.A.J., 56: 249,1947. 22. Holling, H. E., and Zak, G. A.: Cardiac Catheterization in the Investigation of Congenital Heart Disease. Brit. Heart J., 12: 153, 1950. 23. Sancetta, S. M., Hachel, D. B., and Lynn, R. B.: Subendocardial Trauma Produced by Right Sided Catheterization of the Heart in Man. Am. Heart J., 45: 491, 1953. 24. Zimdahl, W. T.: Disorders of the Cardiovascular System Occurring with Catheterization of the Right Side of the Heart. Am. Heart J., 41: 204, 1951. 25. Houssay, H. E. J., Haynes, F. W., and Dextcr, L.: Pulmonary Infarction from Catheterization. Pl'Oc. Soc. Expel'. BioI. & Med., 79: 444, 1952. 26. Schnabel, T. G., Jr., and others: A Technique of Vascular Catheterization with Small Plastic Catheters: Its Utilization to Measure the Arterial Pulse Wave Velocity in Man. Circulation, 5: 257, 1952.
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27. Cournand, A., and others: Report of the Committee on Cardiac Catheterization and Angiocardiography of the American Heart Association. Circulation 7: 769, 1953. 28. Hurst, W. W., and Schemm, F. R.: High Ventricular Septal Defect with Slight Dextro-position of the Aorta (Eisenmenger Type) Which Presented the Clinical Features of Patent Ductus Arteriosus. Am. Heart J., 36: 144, 1948. 29. Ash, R., and Murphy, L.: High Ventricular Septal Defect and Slight Dextroposition of the Aorta (Eisenmenger Complex) Associated with Deformed Aortic Valve Stimulating Patent Ductus Arteriosus. J. Pediat. 37: 249, 1950. 30. Morgan, E. H., and Burchell, H. B.: Ventricular Septal Defect Simulating Patent Ductus Arteriosus. Proc. Staff Meet., Mayo Clin., 25: 69,1950. 31. Swan, H. J. C., Burchell, H. B., and Wood, E. H.: Differential Diagnosis at Cardiac Catheterization of Anomalous Pulmonary Venous Drainage Related to Atrial Septal Defects or Abnormal Venous Connections. Proc. Staff Meet., Mayo Clin., 28: 452, 1953. 32. Huitgren, H., Selzer, A., Purdy, A., Holman, E., and Gerbode, A.: The Syndrome of Patent Ductus Arteriosus with Pulmonary Hypertension. Circulation, 8: 15, 1953. 33. Moffitt, G. R., Jr., Zinsser, H. F., Ruo, P. T., Johnson, J., and Schnabel, T. G., Jr.,: Pulmonary Stenosis with Left to Right Intracardiac Shunts. Am. J. Med., 26: 521, 1954. 34. Broadbent, J. C., Wood, E. H., Burchell, H. B., and Parker, R. L.: Ebstein's Malformation of the Tricuspid Valve: Report of Three Cases. Proc. Staff Meet., Mayo Clin., 28: 27,1953. 35. Engle, M. A., and Taussig, H. B.: Valvular Pulmonic Stenosis with Intact Ventricular Septum and Patent Foramen Ovale. Report of Illustrative Cases and Analyses of Clinical Syndrome. Circulation, 2: 481, 1950. 36. Peterson, L. H.: The Dynamics of Pulsatile Flow. Circulation Research, 2: 127, 1954. 37. Connolly, D. C., Tompkins, R. G., Leo, R., Rirklin, J. W., and Wood, E. H.: Pulmonary Artery Wedge Pressures in Mitral Valve Disease: Relation· ship to Left Atrial Pressures. Proc. Staff Meet., Mayo Clin., 28: 72, 1953. 38. Ankeney, J. L.: Further Experimental Evidence That Pulmonary Capillary Pressures Do not Reflect Cyclic Changes in Left Atrial Pressure. (Mitral Lesions and Pulmonary Embolism). Circulation Research, 1: 58, 1953. 39. Gorlin, R., and Gorlin, S. G.: Hydraulic Formula for Calculation of the Area of the Stenotic Mitral Valve, Cardiac Valves and Central Circulatory Shunts. Am. Heart J., 41: 1, 1951. 40. Yu, P. N. G., Lovejoy, F. W., Jr., Joos, H. A., Nye, R. E., Jr., and Mahoney, E. B.: Right Auricular and Ventricular Pressure Patterns in Constrictive Pericarditis. Circulation, 7: 102, 1953. 41. Hetzel, P. S., Wood, E. H., and Burchell, H. B.: Pressure Pulse in the Right Side of the Heart in a Case of Amyloid Disease and in Case of Idiopathic Heart Failure Simulating Constrictive Pericarditis. Proc. Staff Meet., Mayo Clin., 28: 107, 1953. 42. Wilson, R. H., Borden, C. W., Hoseth, W., Sadoff, C. N., and Dempsey, M. E.: The Pathologic Physiology and Diagnostic Significanee of Pressure Pulses in the Right Heart in Patients with Chronic Constrictive Pericarditis and Pericardial Effusion. Clin. Res. Proc., 2: 9, 1954. 3400 Spruce Street Philadelphia 4, Pa.