Original Article Kurume Medical Journal, 48, 31-35, 2001 Transient Heart Murmur in Late Neonatal Period: Its Origin and Relation to Transition from Fetal to Neonatal Circulation YUMI KIYOMATSU Department of Pediatrics and Child Health and Perinatal Medical Center, Kurume University School of Medicine, Kurume 830-0011, Japan Summary: To elucidate origin of transient murmur during late neonatal period, we examined 50 neonates with this type of murmur and compared m with 50 controls. We serially examined morphology of and blood in main pulmonary artery (MPA), right pulmonary artery (RPA), and left pulmonary arteries (LIDA) using two-dimensional and Doppler echocardiography. The murmurs were first noticed at 6 to 60 days after birth (mean 33 }14). At that time, diameters of both RPA and LPA in murmur group were sig nificantly smaller than those in control group, and velocities of blood in right and left pulmonary arteries in murmur group were significantly greater than those in control group. When murmur disappeared, diameters and velocities of both RPA and LPA were not different compared with control group. Two cases in murmur group continued to have a murmur and were diagnosed as having intrinsic congenital periph eral pulmonary artery stenosis. In conclusion, our findings suggest that a transient murmur in late neonatal period is caused by transient branch pulmonary arteries stenosis during transitional circulation from fetus to neonates. Key words transient murmur, neonate, peripheral pulmonary artery stenosis, perinatal circu lation, Doppler echocardiography INTRODUCTION Several types of transient murmur are detected during neonatal period [1]. In early neonatal period, some of se may be caused by function al shunting of ductus arteriosus or atrial shunting at foramen ovale. In 1971, Kato [2] reported " transient murmur in late neonatal period," which is detected from about 2 to 4 weeks after birth and subsequently disappears after a few months. This murmur is characterized as a moderately pitched early- to mid-systolic ejection murmur at second intercostal space left sternal border, with intensity of Levine 2-3/6. The second sound is some times fixed split. From findings of cardiac caterization and intracardiac phonocardiography in infants with this murmur, Kato concluded that physiological peripheral pulmonary stenosis might contribute to this murmur. In order to elucidate origin of this murmur, we serially examined morphology of and blood in main and peripheral pulmonary arteries using two-dimensional and Doppler echocardiography in 50 infants with this type of murmur, and compared m with those in 50 infants without a murmur. Studied groups METHODS The murmur group consisted of 50 infants with murmur characterized above. All of m were referred to our institution because of ir murmur. The gestational ages at birth were 38 }2.2 weeks, and ir birth weights were an aver- Received for publication November 29, 2000 Correspondence to: Yumi Kiyomatsu, Department of Pediatrics and Child Health, Kurume University School of Medicine. 67 Asahi-machi. Kurume 830-0011, Japan. Tel: +81-942-31-7565 Fax: +81-942-38-1792
32 KIYOMATSU age of 2871 }532g. Their murmurs were first noticed at 6 to 60 days after birth (mean, 33 }14). The control group consisted of 50 infants without any murmurs who visited our institution for rou tine developmental evaluation. Their gestational ages at birth (38 }1.5 weeks) and birth weights (3102 } 507g) were not significantly different from those of murmur group. All infants in both groups were healthy and had normal clinical courses during study period. Two pediatric cardiologists studied auscultation in all infants. Chest X-ray, electrocardiography, phonocar diography, and echocardiography were performed in order to exclude cases of cardiac anomaly. Echocardiography Two-dimensional and Doppler echocardiography were performed using Aloka SSD-730 or SSD-870 (Aloka, Tokyo) with a 5.0 MHz transducer. The diameter of main pulmonary artery (MPA) was measured at middle of pulmonic valve and bifurcation of branch pulmonary arteries. The diameters of right pulmonary artery (RPA) and left pulmonary artery (LPA) were measured at proximal end using standard parasternal short-axis view. For measurement of blood velocity at MPA, a sample volume of pulsed Doppler echocardiography was placed at MPA where maximal velocity was recorded. For mea surement of velocity at RPA and LPA, a sample volume of pulsed Doppler echocardiography was placed at proximal right and left pul monary arteries, respectively. The pressure gradients from MPA to RPA and LPA were calculated using a modified Bernoulli formula. The presence of shunts through ductus arteriosus and foramen ovate were evaluated by color Doppler mapping. Follow-up examinations The infants in murmur group were examined every 2 to 3 months at cardiac clinic until ir murmurs disappeared. The presence of a murmur was evaluated by means of auscul tation and phonocardiogram. The same measurements were obtained by means of echocardiography at each follow-up visit. Statistics The differences between murmur group and control group in terms of each measurement were evaluated by an unpaired t test. For follow up study in murmur group, differences between both periods were evaluated by a paired t test. P values less than 0.05 indicated statistically sig nificant differences between groups. RESULTS Characteristics of murmur and its outcome All infants in murmur group had characteristic murmur, which was an early- to TABLE 1. Comparison of murmur (group A) and control (group B) with peripheral pl umonic artery
TRANSIENT HEART MURMUR mid-systolic ejection murmur at second inter costal left sternal border with an intensity of Levine 33 IN NEONATE of 2-3/6. This murmur radiated widely over eir side or both sides of chest. The quality of murmur was moderately pitched in most cases but soft and high-pitched in about 20% of cases. The second sound was fixed split with a slightly increased pulmonary component in 32 cases (64%). Phonocardiograms revealed a crescendo-decrescendo (diamond-shaped) early- to mid-systolic murmur (Fig. 1). It was observed at follow-ups that murmur disappeared at 33 to 190 days (mean, 118 days) after birth for 48 of 50 cases in mur mur group. The second sound had become a normal respiratory split in all cases. However, murmur continued to be heard in remaining two cases (4%). The intensity of pulmonic com ponent of second sound increased in both cases. These cases were diagnosed as intrinsic con genital peripheral pulmonary artery stenosis (Fig. 2). Echocardiographic The echocardiographic in Table arteriosus. through diagnosed as patent in foramen were group. in both murmur RPA and RPA had since shunt were width was heard, smaller than those meantime, in and LPA LPA Fig. 1. Serial evaluation of phonocardiograms and pulse Doppler echocardiograms in a case of transient murmur. A: Heart murmur was detected at 14 days after birth. Diameters of both branch pulmonary arteries were relatively small compared with that of main pulmonary artery. The velocity at right pulmonary artery was 2.45 m/sec. Phonocardiogram revealed a moderate- to high-pitched ejection systolic murmur at second intercostal left sternal border. B: The murmur disappeared at 5 months of age. The diameters of both branch pul monary arteries grew large, and velocity at right pulmonary artery decreased to 1.43 m/sec. Kururn,e Medical Fig. 2. Two of 50 cases in murmur group continued to have murmur and were diagnosed as having intrinsic peripheral pulmonary artery stenosis. The velocity (Vmax) at bifurcation of pulmonary artery gradually increased during follow-up. Journal Vol. 48, No. 1, 2001 at in significantly cases shown 3mm. In are no shunt All of m ovale, control velocities of time of both was septum. was less than group Some murmur re interatrial of shunt At measurements 1. In all studies, ductus diameters findings
34 KIYOMATSU Fig. 3. Serial measurement of ratio of velocity (Vmax) at right pulmonary artery to main pulmonary artery (RPA/MPA) [left panel], and left pulmonary artery to main pulmonary artery (LPA/MPA) [right panel]. At time when murmur was detected, both RPA/MPA Vmax ratio and LPA/MPA Vmax ratio in transient murmur group were significantly greater than those in control group (p=.0001). When murmur disappeared, both RPA/MPA Vmax ratio and LPA/MPA Vmax ratio in transient murmur group decreased and were not significantly different from those in control group. murmur group were significantly faster than those in control group. The pressure gradient was 15.4 to 30.2 mmhg between MPA and RPA, and 15.8 to 36.2 mmhg between MPA and LPA (Fig. 3). The diameter and velocity at MPA were not significantly different between murmur and control groups. According to follow-up echocardiography at time murmur disappeared, diameters of both RPA and LPA had significantly increased, and velocities in both RPA and LPA had significantly decreased. Although diameter of MPA had significantly increased during same period, RPA/MPA and LPA/MPA diameter ratio had significantly increased, which represented fact that growth of diameters of RPA and LPA were greater than those of MPA. DISCUSSION Transient murmur in late neonatal period was first described by Kato in 1971[2]. This murmur is noted during late neonatal period and subsequently disappears after a few months. Kato had examined 3 infants with this murmur by means of intracardiac phonocardiography and cardiac cater ization. He found that this murmur originated at bifurcation of RPA and LPA and that re was a mild pressure gradient at se sites. Soon after, Dunkle and Rowe reported same transient mur mur described as "simulating pulmonary artery stenosis" in premature infants [3]. The serial echocardiographic evaluation in present study clearly demonstrated relation between this transient murmur and transient branch pulmonary arteries stenosis. Infants with this transient murmur had branch pulmonary arter ies with significantly smaller diameters and with faster velocities than those without mur murs. Furrmore, after a few months, se smaller diameters and faster velocities of branch pulmonary arteries came within a normal range when murmur disappeared. These longitudinal morphological and physiological changes proved that this type of transient murmur is caused by transient branch pulmonary arteries stenosis. The cause of this transient stenosis of branch
TRANSIENT HEART MURMUR IN NEONATE 35 pulmonary arteries can be explained by changes from fetal to neonatal circulation. During fetal period, most of blood from right ven tricle passes through ductus arteriosus [4]. Only about 20% of total cardiac output enters lungs via branch pulmonary arteries, and hence, diameters of branch pulmonary arteries are rela tively small compared with that of MPA. After birth, ductus arteriosus closes within a few days. Then, all of blood from right ventricle sud denly starts to pass through se relatively narrow branch pulmonary arteries [5]. After a few weeks, resistance of pulmonary artery declines, and pressure gradients from MPA to RPA or to LPA occur [6]. Danilowicz et al. [7] reported se phys iologic pressure differences between MPA and branch pulmonary arteries in infants. After that, diameters of branch pulmonary arteries grow as we showed in present study, and pressure gra dients may disappear in about a few months. These perinatal hemodynamical changes may cause tran sient stenosis of branch pulmonary arteries [8,9]. Or hemodynamical changes in neonatal period are thought to cause murmurs. In partic ular, shunt s through ductus arteriosus and foramen ovale dramatically change during neonatal period. The closing of ductus arte riosus is one of causes of murmurs in early neonatal period [1]. However, this ductal may not contribute to transient murmurs in late neonatal period because we did not find ductal shunt in any infants in murmur group when murmur appeared. Although a left-to-right shunt through foramen ovale was detected in some cases, it is unlikely that this shunt contributes to transient murmur. The amount of blood must be trivial since width is less than 3 mm and may not increase at pulmonary artery. In a clinical setting, diagnosis of a transient murmur needs particular attention in order to make a differential diagnosis from congenital disease, such as mild pulmonary stenosis, atrial septal defect, or organic pulmonary artery stenosis. In particular, findings of this murmur are quite similar to those of intrinsic peripheral pulmonary arteries steno sis. In fact, 2 of our 50 cases with this type of murmur actually had an intrinsic abnormality. Hence, it is very important to follow neonate with this murmur until murmur disappears in order to exclude possibility of an intrinsic abnor mality. ACKNOWLEDGMENTS: The author would like to thank Professor Hirohisa Kato, Chairman of Department of Pediatrics and Child Health, for his helpful comments and advice and also Dr. Yasuki Maeno for his technical REFERENCES cooperation. 1. Long WA. Fetal and Neonatal Cardiology, Saunders, Philadelphia, pp 230-233,1990. 2. Kato H. Transient murmur in late neonatal period: Intracardiac phonocardiographic study. Cardiovasc Sound Bull 1971;1:31-38. 3. Dunkle LM. Transient murmur simulating pulmonary artery stenosis in prenature infants. Am J Dis Child 1972; 124:666-670. 4. Heymann MA. Fetal and postnatal circulation. In: Heart Disease in Infants, Children and Adolescents, ed. Moss AJ and Adams FH, Williams & Wilkins, Baltimore, pp 41-46,1995. 5. Marato E, and Fouron JC. Closure of ductus arterio sus; determinant factor in appearance of transient peripheral pulmonary stenosis of neonate. J Pediatr 1991;119:955-959. 6. Rodriguez RJ. Physiologic peripheral pulmonic stenosis in infancy. Am J Cardiol 1990; 66:1478-1481. 7. Danilowicz DA, and Rudolph AM. Physiologic pressure difference between main and branch pulmonary arteries in infants. Circulation 1972; 45:410-419. 8. Yanagawa Y, and Takahashi S. A cause of transient sys tolic murmur in neonates: Diagnosis and prognosis of transient pulmonary artery stenosis at bifurcation. Jpn J Pediatr 1991; 95:1805-1811. (in Japanese) 9. Kimura K, Sekiya C, Sakkuma M, and Itoh M. Relationship between physiologic stenosis at bifur cation of main pulmonary artery and a functional murmur in neonatal period. Jpn J Pediatr 1991; 95:5-8. (in Japanese)