Andersons pediatric cardiology 1082

Epidemiology The factors responsible for persistent ductal patency beyond the first days of life are not fully understood An increased incidence is seen in the premature neonate due to physiologic factors more related to prematurity rather than an inherent abnormality of the duct.41 In infants born at term, persistent patency occurs sporadically, but there is increasing evidence that genetic factors, or prenatal infection, play a role in many children The estimated incidence lies between 1 in 2000 and 1 in 5000 live births.43–45 Persistent patency of the duct accounts for approximately 12% of all congenital cardiac malformations The most extensive study from a relatively homogeneous population was that performed by Carlgren,45 when he charted the incidence of congenital cardiac disease to children born in the Swedish City of Gothenburg Persistent ductal patency was the third most common lesion identified, representing approximately 0.04% of live births If children with the so-called silent duct are included, found incidentally by echocardiography performed for another reason, the incidence may be as high as 1 in 500.46 A significantly higher incidence of ductal patency is also seen in infants born with low weight, patency being found in almost half of infants weighing less than 1750 g at birth, and up to 80% of those weighing less than 1200 g (see also Chapter 15) Genetic Factors Unlike premature infants, as noted earlier, where persistent ductal patency is more often due to developmental immaturity, in the infant born at term there is likely a structural abnormality There is also an increased frequency in several genetic syndromes, such as those with defined chromosomal aberrations, examples being trisomy 21, 14q- and 4p- syndromes, the Rubinstein-Taybi and CHARGE syndromes, single-gene mutations such as Carpenter and Holt-Oram syndromes, and X-linked mutations such as incontinentia pigmenti Although most cases of persistent patency are sporadic, many are also believed to be due to a multifactorial inheritance pattern, with a genetic predisposition and an environmental trigger that occurs at a vulnerable time.47 Females predominate in a ratio of greater than 2 to 1 The mode of inheritance appears to be autosomal recessive with incomplete penetrance.48 In a family having one sibling with a patent duct, there is approximately a 3% chance of a persistent duct in a subsequent offspring47 and a higher risk to the offspring given one affected parent, some 45 times greater than the that for the general population The risk to further children in sibships where two children have been affected is probably in the order of 10% and increases with each affected child Infection and Environmental Factors Maternal rubella during the first trimester of pregnancy, particularly in the first 4 weeks, is associated with a high incidence of a persistently patent arterial duct.49,50 The histology resembles that of a very immature duct, with an extensive subendothelial elastic lamina, thought to retard anatomic sealing.51 Additional environmental factors have been reported associated with persistence, such as in fetal valproate syndrome,52 or after thalidomide.53 A patent arterial duct may be more likely to be found in infants born at high altitude.54 Pathophysiology Persistent patency results in shunting of blood from one side of the circulation to the other, the volume of flow depending on the length and internal diameter of the duct and on the systemic and pulmonary vascular resistances Because pulmonary resistance is usually much lower than systemic, the flow is from the aorta to the pulmonary trunk Hence flow to the lungs is increased, resulting in left atrial and left ventricular volume overload If the duct is widely patent, flow depends entirely on the ratio of resistances Right ventricular failure may occur in the presence of a large duct with pulmonary hypertension or pulmonary edema, and an elevated left atrial pressure In most patients, the duct is partially constricted and the major factor limiting flow Under these conditions, pulmonary arterial pressure is normal or only mildly elevated Symptoms and clinical findings are largely determined by the magnitude of the shunt Clinical Features Most patients are asymptomatic, the lesion recognized with detection of the characteristic murmur Occasionally, there may be a history of prematurity or asphyxia during birth Children with large shunts may fail to thrive, experience difficulty with feeding during infancy, and frequently suffer recurrent infections of the upper respiratory tract Occasionally, congestive heart failure develops Physical Examination There is retarded growth in approximately one-third of children They are acyanotic in the absence of complicating factors The peripheral pulses are easily palpable, with a rapid upstroke and decay There is a widened pulse pressure, with lowering of the diastolic component Arterial pulsation in the neck may be prominent in those with large shunts The precordial examination reveals an active cardiac impulse, with the forceful cardiac apex displaced to the left When the shunt is small, the only abnormal finding may be the murmur The continuous, or “machinery,” murmur of the uncomplicated persistent duct is best heard in the left infraclavicular area, although it is occasionally maximal at the third left interspace Gibson's13 description of the murmur as quoted by Tynan14: It begins quite obviously after the commencement of the first sound It is continued during the latter part of that sound and the whole of the short pause It persists throughout the second sound and dies away gradually during the long pause The murmur is distinctly rough and thrilling in its character It begins, however, somewhat softly, and increases in intensity to reach its acme just about, or immediately after, the incidence of the second sound, and from that point wanes until its termination The second sound can be heard to be loud and clanging and when carefully analyzed it is the pulmonary part of that sound which is accentuated Turbulent flow through the duct itself causes the murmur Additional murmurs may be present due to increased flow across the aortic valve, producing an ejection systolic sound, and across the mitral valve, giving a diastolic murmur with loud onset The systolic component of the continuous murmur may be transmitted into the neck, may be associated with a thrill in the second left intercostal space, or may increase in intensity during inspiration due to a fall in pulmonary vascular resistance Many patients with loud continuous murmurs also have multiple “clanging” sounds These are relatively localized to the pulmonary area and are most frequent in the second half of systole, corresponding to the period of peak flow within the duct Neill and Mounsey55 attributed these sounds to the turbulence caused by the “head on” collision of opposed flow from the duct and the right ventricle and named them eddy sounds