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Differential Diagnosis of by Means of Intracardiac Phonocardiography

Tadashi KAMBE, M.D., Tadayuki KATO, M.D., Norio HIBI, M.D., Yoichi FUKUI, M.D., Takemi ARAKAWA, M.D., Kinya NISHIMURA,M.D., Hiroshi TATEMATSU,M.D., Arata MIWA, M.D., Hisao TADA, M.D., and Nobuo SAKAMOTO,M.D.

SUMMARY The purpose of the present paper is to describe the origin of the systolic murmur in pulmonic stenosis and to discuss the diagnostic pos- sibilities of intracardiac phonocardiography. Right catheterization was carried out with the aid of a double- lumen A.E.L. phonocatheter on 48 pulmonic stenosis patients with or without associated heart lesions. The diagnosis was confirmed by heart catheterization and angiocardiography in all cases and in 38 of them, by surgical intervention. Simultaneous phonocardiograms were recorded with intracardiac pressure tracings. In valvular pulmonic stenosis, the maximum ejection systolic murmur was localized in the pulmonary above the pulmonic valve and well transmitted to both right and left pulmonary , the , and right and left atria. The maximal intensity of the ejection systolic murmur in infundibular stenosis was found in the outflow tract of right . The contractility of the infundibulum greatly contributes to the formation of the ejection systolic murmur in the outflow tract of right ventricle. In , the major systolic murmur is caused by the pulmonic stenosis, whereas the high ventricular septal defect is not responsible for it. In pulmonary branch stenosis, the sys- tolic murmur was recorded distally to the site of stenosis. Intracardiac phonocardiography has proved useful for the dif- ferential diagnosis of various types of pulmonic stenosis. Additional Indexing Words: Right heart catheterization Pulmonic valvular stenosis Infundibular stenosis Pulmonary branch stenosis

NTRACARDIAC phonocardiography, introduced by Yamakawa in 1953,1) was a breakthrough in the realm of clinical phonocardiography. Since the advent of this method, it has served as a useful tool for differential diagno-

From the Third Department of Internal , Nagoya University, School of Medicine , Tsurumai-cho 65, Showa-ku, Nagoya 466, Japan. Received for publication December 8, 1975. 691 NJap. Heart J. 692 KAMBE, ET AL. ovember, 1976 sis, thus contributing to the analysis of the origin of the cardiac murmurs and sounds in heart chambers or . In general, conventional external phonocardiography is non-invasive and simple, but may not always correctly reflect the acoustic events occurring in the cardiac chambers or great vessels. In contrast, intracardiac phono- cardiography can localize the origin of cardiac murmurs or sounds in a wide variety of cardiovascular diseases and may detect the result of small eddies that are usually inaudible on the chest surface. Since the introduction of intracardiac phonocardiography, many pub- lications2)-10) have discussed the origin of the systolic murmurs in pulmonic stenosis. Recently, Lequime et al11) reported on the origin of systolic mur- murs in pulmonic stenoses of different types, comparing intracardiac phono- cardiography with angiocardiography. The purpose of the present study is to describe the origin and transmission of the systolic murmurs in pulmonic stenosis of various types, and to discuss the diagnostic possibilities of intracardiac phonocardiography.

MATERIAL AND METHODS Right heart catheterization using intracardiac phonocardiography was carried out on 48 pulmonic stenosis patients with or without associated cardiac anomalies. The age ranged from 3 to 41 years. The cardiac diagnosis of the subjects, as shwon in Table I, was confirmed by heart catheterization and angiocardiography. Of

Table I. Materials

Abbreviations: PS: pulmonic stenosis, ASD: , VSD: ventricular septal defect, PLSVC: persistent left superior vena cava, PAPVD: partial anomalous pulmonary venous drainage, T/F: tetralogy of Fallot, Pul.: pulmonic.

* The manufacturer of the phonocatheter is A .E.L. (American Electric Laboratories Inc.), P.O. Box 552, Lansdale, PA. 19446, U.S.A. Vol.17 No.6 INTRACARDIAC PHONOCARDIOGRAPHY 693 the 48 patients, the diagnosis of 38 was eventually verified by surgical intervention. A double-lumen phonocatheter of A.E.L.,* with barium titanate on the tip, was introduced into the left axillary vein and advanced to the via superior vena cava, right and ventricle. All procedures of heart catheteriza- tion were performed in the sedated and postabsorptive state after informed consent was obtained. In the majority of cases, a simultaneous recording of intracardiac and external phonocardiograms was made in conjunction with intracardiac pres- sure tracing with the aid of a polygraph (Fukuda-denshi EMR-100R) and a photo- graphic recorder (Sanei-sokki 100A). A pressure transducer TM-1 was used for the pressure tracing and a contact microphone (Fukuda-denshi MA-250 or PM-1) was applied to the chest surface where the maximum murmur was audible. Paper speed was 100mm/sec in the majority of cases, and intracardiac murmurs were usually investigated in the pulmonary artery of both sides from the main trunk to the periphery, right ventricle, right atrium and superior vena cava. In 9 cases the left atrium was entered and a systolic murmur was recorded. During the recording of systolic murmurs, the phonocatheter was manipulated with great care and the withdrawal from the pulmonary artery into the right ventricle was repeated very slowlywith caution, since the outflow tract may produce artificial extrasounds.

RESULTS I. Valvular Pulmonic Stenosis In all subjects with valvular pulmonic stenosis, the maximum ejection

Fig.1. A simultaneous recording of intracardiac and external phono- cardiograms with pressure tracing of main pulmonary artery in a 19-year-old male (N.S.). The intracardiac indicates a localization of the maximum ejection systolic murmur in the pulmonary artery just above the pulmonic valve. Abbreviations: I-PCG=intracardiac phonocardiogram , PCG=external phonocardiogram, PA=pulmonary artery, 2L=the second left intercostal space, SM=systolic murmur, IIP=the pulmonary component of the second heart sound. Jap. HeartJ. 694 KAMBE, ET AL. November, 1976

Fig.2. A 19-year-old female with moderate pulmonic stenosis and func- tional infundibular stenosis. Note the ejection systolic murmur in the pulmo- nary artery just above the valve (upper panel), whereas a late systolic murmur is found in the outflow tract of right ventricle (lower panel). The latter is thought to be due to the functional infundibular stenosis. Abbreviations: RV=right ventricle, 3L=the third left intercostal space. Other abbreviations as in Fig.1.

systolic murmur was recorded in the pulmonary artery just above the pul- monic valve, radiating from the main pulmonary trunk to the periphery of left and right pulmonary arteries. Fig.1 demonstrates an example of mild valvular stenosis (19-year-old male, N.S.). Simultaneous registration of in- tracardiac and external phonocardiograms was made together with the pres- sure tracing of the main pulmonary artery. The intracardiac phonocardio- gram (I-PCG) indicates a localization of the maximum ejection systolic murmur in the pulmonary artery just above the pulmonic valve. The interval of the second heart sound splitting amounted to 80 msec, and the pressure gradient across the pulmonic valve was 37mmHg in systole. There was no systolic murmur in the outflow tract of right ventricle. Moreover, right Vol.17 INTRACARDIAC PHONOCARDIOGRAPHY 695 No.6

Fig.3. A mode of propagation of systolic murmur from the pulmonary artery to the right atrium (upper panel) and superior vena cava (lower panel) in a 26-year-old female with valvular pulmonic stenosis associated with partial pulmonary venous return draining into left innominate vein through vertical vein. In the right atrium and superior vena cava, there are ejection systolic murmurs which are considered to be propagated from the pulmonary artery. Abbreviation: RA=right atrium, SVC=superior vena cava. Other ab- breviations as in Fig.1. ventriculography did not prove the presence of functional infundibular steno- sis. In moderate or severe valvular pulmonic stenosis, a late systolic murmur was demonstrated in the outflow tract of right ventricle, which corresponded to the findings obtainded by the selective angiocardiography of right ven- tricle. Fig.2 shows a simultaneous registration of intracavitary and external phonocardiograms with intracardiac pressure in a 19-year-old female with moderate valvular pulmonic stenosis and functional infundibular stenosis (Y.S.). The diagnosis was corroborated by open heart , and the systolic pressure gradient across the pulmonic valve was found to be 80mmHg. The intracardiac phonocardiogram revealed that the largest ejection systolic murmur was just above the pulmonic valve, whereas a late systolic murmur Jap. Heart J. 696 KAMBE, ET AL. November, 1976 was found in the outflow tract of right ventricle. The latter can be attributed to a functional infundibular stenosis. In valvular pulmonic stenosis with or without associated heart anomalies, an ejection systolic murmur was also recorded in the superior vena cava in 15 out of 19 cases, and in the right atrium in 18 out of 25 patients. This phenomenon is explained by a transmission from the pulmonary artery, due to their close relationship. Fig.3 illustrates a mode of propagation of systolic murmur from the pulmonary artery to the right atrium (upper panel) and superior vena cava (lower panel) in a 26-year-old female. The patient was diagnosed as having valvular pulmonic stenosis with partial anomalous pulmo- nary venous return draining into the left innominate vein through the vertical vein. The intracardiac phonocardiogram shows that, in the right atrium and superior vena cava, there are ejection murmurs which are apparently trans- mitted from the pulmonary artery. In valvular pulmonic stenosis associated with atrial septal defect, it is

Fig.4. Intracardiac phonocardiograms show ejection systolic murmurs in the pulmonary artery (upper panel) and left atrium (lower panel). The murmur in the latter is considered to be transmitted from the pulmonary artery. Abbreviations: LA=left atrium, others as in Fig.1. An 8-year- old female with valvular pulmonic stenosis and atrial septal defect. Vol.17 No.6 INTRACARDIAC PHONOCARDIOGRAPHY 697 noteworthy that both lesions generate ejection systolic murmurs in the pulmo- nary artery due to different mechanisms; the former produces a systolic eddy by a pressure gradient across the pulmonic valve while the latter does so by an increase of pulmonary blood flow. In 3 cases associated with atrial septal defect, a continuous murmur was recognized at the defect area. It corresponds to the v murmur postulated by Sakamoto, since its peak is closely related to the atrial v wave. However, no continuous murmur was found in patients with a reversed shunt. In 5 cases, the left atrium was entered accidentally during catheteriza- tion, and an ejection systolic murmur was also recorded. The latter was thought to be transmitted from the pulmonary artery. Fig.4 demonstrates an example of intracardiac phonocardiogram from an 8-year-old female with valvular pulmonic stenosis associated with atrial septal defect (H.K.). Note the ejection systolic murmur in the pulmonary artery and left atrium; in the former (upper panel), there are additionally the first heart sound and the pulmonic component of the second sound, while, in the latter (lower panel), the ejection systolic murmur appears to be domi- nant. In this subject the systolic pressure gradient across the pulmonic valve was 60mmHg and the atrial septal defect measured 3.0 by 1.5cm in diameter. In the present cases, the ejection systolic murmur was well transmitted to the left atrium from the pulmonary artery in contrast to the first and second heart sounds. In valvular pulmonic stenosis complicated by ventricular septal defect (normal aortic root), the major systolic murmurs were classified into 2 pat- terns; one was due to valvular pulmonic stenosis and the other to ventricular septal defect. In the main pulmonary artery, an ejection systolic murmur was recorded, whereas a holosystolic murmur was noted in the right ventricle. However, it should be borne in mind that isolated high-positioned ventricular septal defect may produce a rather loud systolic murmur in the pulmonary artery, as well as a holosystolic murmur in the outflow tract of right ven- tricle. II. Organic Pulmonic Infundibular Stenosis In organic infundibular stenosis, the ejection systolic murmur was loudest in the outflow tract of right ventricle but the intensity diminished in the pulmonary artery and apex of right ventricle. The ejection systolic murmur was explained by the systolic pressure gradient between infundibulum and inflow tract of the right ventricle. Fig.5 demonstrates a simultaneous recording of intracardiac and external phonocardiograms with intracardiac pressure in a 19-year-old female with organic infundibular and valvular pul- monic stenosis (H.Y.). Two intracardiac pressure gradients were found Jap. Heart.J. N 698 KAMBE, ET AL. ovember, 1976

Fig.5. A 19-year-old female with organic infundibular and valvular pulmonic stenosis (H.Y.). The intracardiac phonocardiograms indicate a mid-systolic murmur in the main pulmonary artery (left panel) and a late systolic murmur in the infundibulum of the right ventricle (middle panel); the former is due to valvular stenosis while the latter due to infundibular stenosis. The murmur is diminished in the apex of right ventricle (right panel). Abbreviations as in Fig.1. across the pulmonic valve and between the inflow and outflow tracts of the right ventricle in systole. The intracardiac phonocardiogram shows an ejec- tion systolic murmur with a mid-systolic peak in the main pulmonary artery just above the valve while, in the right ventricular infundibulum, there is another ejection systolic murmur with a late systolic peak; the former is due to valvular stenosis and the latter to infundibular stenosis. In the apex of right ventricle, the murmur is diminished. The cardiac diagnosis was con- firmed by selective angiocardiography of right ventricle and surgical interven- tion. In a 19-year-old male (K.O.) with organic infundibular stenosis associated with high-positioned ventricular septal defect, the maximum systolic murmur was localized to the outflow tract of right ventricle and two murmurs, caused by the two lesions, blended in the infundibulum of right ventricle. The intracardiac phonocardiogram revealed that the systolic murmur was pro- pagated to the main pulmonary artery; however, it spontaneously disappeared on withdrawal of the phonocatheter from the infundibulum into the apex of the right ventricle. The associated ventricular septal defect measured 2.0cm in diameter at operation. III. Tetralogy of Fallot In 13 patients with tetralogy of Fallot, the right ventricle and pulmonary artery were investigated with the phonocatheter and, accidentally, the and left ventricle were explored in 3 cases using intracardiac phonocardio- graphy. Our findings suggest that the major systolic murmur of tetralogy depended upon the associated pulmonic stenosis, regardless of valvular or infundibular type. Of 13 subjects examined, 11 had infundibular stenosis, Vol.17 No.6 INTRACARDIAC PHONOCARDIOGRAPHY 699

Fig.6. A 21-year-old patient with tetralogy of Fallot (T.S.). A loud systolic murmur is described in the outflow tract of right ventricle, transmit- ting to the pulmonary artery but diminishing in the apex of right ventricle. revealing the maximum ejection systolic murmur in the outflow tract of right ventricle. The high ventricular septal defect was not thought to be responsible for the formation of the major systolic murmur since there was no significant pressure gradient between right and left ventricles and, moreover, the ven- tricular septal defect was too large to generate such a loud murmur. Fig.6 demonstrates a simultaneous registration of intracardiac and ex- ternal phonocardiograms on a 21-year-old male with tetralogy of Fallot (T.S.). A loud systolic murmur is noted in the outflow tract of right ventricle, well transmitted to the pulmonary artery but diminishing in the apex of right ventricle. The diagnosis was confirmed by complete surgical repair. In general, the left side of heart may not play an important role in the genesis of the major systolic murmur in tetralogy. On the other hand, the Jap. HeartJ. N 700 KAMBE, ET AL. ovember, 1976

Fig.7. An example of multiple pulmonary branch stenoses (32-year- old female, T.H.). An ejection systolic murmur is found in the right pulmo- nary artery distal to the site of stenosis (upper panel); it disappears on with- drawal of phonocatheter into the main pulmonary artery. A diastolic mur- mur due to pulmonic regurgitation appears in the right ventricular outflow tract (lower panel). RPA=right pulmonary artery, DM=diastolic mur-

mur. systolic murmur of this lesion is frequently transmitted to the superior vena cava and right atrium, and is occasionally recorded in the left atrium. IV. Pulmonary Branch Stenosis In pulmonary branch stenosis, the systolic murmur was localized in the pulmonary branch beyond the site of stenosis in our 3 cases. A systolic pres- sure gradient between the proximal and distal portions of the pulmonary branch stenosis is considered to be responsible for the genesis of the murmur. In 1 patient with pulmonary hypertension, a continuous murmur was recorded beyond the site of stenosis in the pulmonary artery branch. Fig.7 indicates an example of multiple pulmonary branch stenoses in a 32-year-old female, in whom the clinical diagnosis was aortitis. The intra- cardiac phonocardiogram shows an ejection systolic murmur in the right pulmonary artery that disappears on withdrawal of the phonocatheter into the main pulmonary artery just above the pulmonic valve. A diastolic murmur appears in the right ventricle, caused by associated pulmonic regurgitation. As a result, pulmonary branch stenosis can be differentiated from valvular stenosis through the localization of the murmur by means of intracardiac phonocardiography. Vol.17 INTRACARDIAC PHONOCARDIOGRAPHY 701 No.6

DISCUSSION Intracardiac phonocardiography has been utilized to localize the heart murmurs and sounds in a wide variety of cardiac diseases and has thus proved useful in the differential diagnosis. A major advantage of this method is that it may detect the origin of these intracardiac acoustic events at the site of origin and may even reveal slight murmurs that are inaudible on the chest surface. The maximum ejection systolic murmur in valvular pulmonic stenosis was invariably obtained in the pulmonary artery just above the valve. The systolic pressure gradient across the pulmonic valve is the cause of production of the ejection systolic murmur. It should be pointed out that the contraction of the infundibulum causes a late systolic murmur in the right ventricle.11) From the present findings, functional infundibular stenosis would appear to be slight in mild valvular pulmonic stenosis, whereas, in advanced valvular stenosis, the outflow tract of right ventricle may intensively contract in late systole and greatly contribute to the formation of a late systolic murmur in the infundibulum.11) However, in order to confirm a functional infundibular stenosis, it is necessary to perform biplane angiocardiography, and we have performed a comparative study of intracardiac phonocardiography and angiocardiography. The mode of transmission of the ejection systolic murmur generated in the pulmonary artery deserves discussion. During catheterization, the left atrium was at times accidentally entered through an atrial septal defect or probe patent foramen ovale, and a loud ejection systolic murmur was recorded, although, in pulmonic stenosis, there is no mechanism which would generate a systolic bruit in the left atrium in contrast to mitral regurgitation. It is likely that the ejection systolic murmur was propagated from the adjacent pulmonary artery, for the appendage is in a close proximity to the pulmonary artery and may easily be affected by acoustical events of the latter. Accord- ing to Perry,12)the intensity of the murmur in the left atrium is proportional to the loudness of the systolic murmur in the pulmonary artery. In addition, the timing characteristics and configuration of the murmurs are similar. This is also true of the systolic murmur in the superior vena cava and right atrium since the former is adjacent to the right pulmonary artery. As already mentioned, in valvular pulmonic stenosis, the maximal ejec- tion systolic murmur was localized in the main pulmonary artery just above the pulmonic valve and was propagated to both left and right pulmonary arteries. However, it should be kept in mind that the double-lumen phono- catheter of A.E.L. may contact the pulmonary arterial walls, and thus may Jap. HeartJ. N 702 KAMBE, ET AL. ovember, 1976

produce artifactual extrasounds and murmurs. When there is an associated atrial septal defect, the intracardiac phono- cardiogram displays a continuous murmur13) at the defect area in the right atrium of patients with left-to-right shunt, a finding not present in subjects with reversed shunt, as in trilogy of Fallot. The continuous murmur has been designated by Sakamoto14) as v murmur, since it has close relationship with the atrial v wave. In short, the evidence of v murmur or mid-diastolic due to relative tricuspid stenosis in the inflow tract of the right ventricle suggests the combination of atrial septal defect and pulmonic stenosis. On the con- trary, both pulmonic stenosis and atrial septal defect produce a similar ejection systolic murmur in the pulmonary artery. In pulmonic stenosis associated with ventricular septal defect, it is note- worthy that a holosystolic murmur15) is found in the right ventricle due to a jet from the left ventricle while, in the pulmonary artery, an ejection systolic murmur occurs as a result of a systolic pressure gradient across the pulmonic valve. However, as the pulmonic stenosis progresses and the right ventricular pressure rises, the systolic murmur of the right ventricle disappears, due to a diminution of left-to-right shunt at the ventricular level. The authors' ex- perience suggests that attention should be paid to the intracavitary murmurs of high-positioned ventricular septal defect, in which a loud systolic murmur occurs due to a strong jet toward the pulmonary artery, as well as toward the right ventricle. Diagnostic failure through dependence solely upon analysis of intracardiac phonocardiograms may be avoided by making simultaneous pressure tracings. Intracardiac phonocardiography has another limitation for the diagnosis of complex cardiac anomalies; for example, a case of pulmonic stenosis with was not detected by this method and was later ascer- tained by cardiac surgery. In patent ductus arteriosus, the continuous murmur is dominant in the pulmonary artery from the standpoint of intra- cardiac phonocardiography.4) The patient mentioned here revealed no sig- nificant continuous murmur in the pulmonary artery but only an ejection systolic murmur. Selective aortography may be necessary for the detection of the lesion. In tetralogy of Fallot, the large ventricular septal defect is not considered to cause the systolic murmur15) while the pulmonic stenosis is responsible for the harsh systolic murmur heard over the mid-precordium.4) Moreover , in the left ventricle, there was no large shunt murmur in the 2 cases accidentally investigated. This further supports the theory that a large, high ventricular septal defect in tetralogy is acoustically silent.15-17) In tetralogy, there was only a slight aortic systolic murmur, either functional or transmitted from the Vol.17 INTRACARDIAC PHONOCARDIOGRAPHY 703 No.6 pulmonary artery. Intracardiac phonocardiography has provided useful information for the diagnosis of pulmonary branch stenosis; the systolic murmur is located in the distal area to the stenosis,18)-20)in contrast to that of valvular stenosis. One can detect systolic murmurs in unusual sites due to the multiple stenoses. The distribution of systolic murmurs on the chest surface is influenced by the location of the stenotic areas. Since these sites of obstruction are usually multiple and involve the main pulmonary artery as well as the proximal and distal branches, it is understandable that the systolic murmur is characterized by a wide thoracic distribution so that it is heard not only at the pulmonic area but also in the axillae and back.19) The systolic murmur is also recorded at the junction of superior vena cava and right atrium, a point which is close to the secondary divisions of the right pulmonary artery.21) It is most likely a transmitted murmur. In pulmonary hypertension due to multiple peripheral stenoses, a continuous murmur may be audible due to the blood flow through the stenosis in both systole and diastole. Study of the pressure curves proximal and distal to a stenosis shows the marked pressure gradient throughout the entire cardiac cycle.22) The limitation of the present method is the difficulty involved in obtain- ing the murmurs in the distal areas of stenosis in bilateral multiple pulmonary branch stenoses, since the tip of phonocatheter may not reach the site of the murmurs. Also, it should be borne in mind that insertion of phonocatheter may aggravate the stenosis originally existing in the distal pulmonary artery. Recently, a range-gated, pulsed Doppler flowmeter was developed to measure the average velocity of flow within a small volume at any point along an ultrasonic beam.23) Johnson and associate 24)have applied this method to the localization of cardiac murmurs in congenital and acquired heart diseases, and found that, in pulmonic stenosis with outflow tract obstruction of the right ventricle, all subjects had a marked turbulence in the pulmonary trunk or at the pulmonic valve orifice. However, the same authors stated that valvular or subvalvular stenosis could not be distinguished. Intracardiac phonocardiography has led to a better understanding of the genesis and the transmission of the heart murmurs and sounds; this method, though invasive, makes it very useful for the differentiation of various murmurs caused by pulmonic stenosis and, as such, a key to the diagnosis.

ACKNOWLEDGEMENT We thank Dr. Aldo A. Luisada for his advice in preparing this manuscript. Jap. HeartJ. N 704 KAMBE, ET AL. ovember. 1976

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