Огляд вроджених серцево-судинних аномалій

1. 1. Materna-Kiryluk A, Wiśniewska K, Badura-Stronka M, et al: Parental age as a risk factor for isolated congenital malformations in a Polish population. Paediatr Perinat Epidemiol 23(1):29-40, 2009. doi: 10.1111/j.1365-3016. 2008.00979.x

2. 2. Russell MW, Chung WK, Kaltman JR, Miller TA: Advances in the understanding of the genetic determinants of congenital heart disease and their impact on clinical outcomes. J Am Heart Assoc 7(6):e006906, 2018. doi:10.1161/JAHA.117.006906

3. 3. van der Linde D, Konings EEM, Slager MA, et al: Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol  58(21):2241–2247, 2011. doi: 10.1016/j.jacc.2011.08.025

4. 4. Pierpont ME, Brueckner M, Chung WK, et al: Genetic Basis for Congenital Heart Disease: Revisited: A Scientific Statement From the American Heart Association [published correction appears in Circulation 2018 Nov 20;138(21):e713]. Circulation 138(21):e653–e711, 2018. doi:10.1161/CIR.0000000000000606

5. 5. Freeze SL, Landis BJ, Ware SM, Helm BM: Bicuspid aortic valve: a review with recommendations for genetic counseling. J Genet Couns 25(6):1171–1178, 2016.

Profound changes to this system occur after the first few breaths, resulting in

• Increased pulmonary blood flow

• Functional closure of the foramen ovale

Pulmonary arteriolar resistance drops acutely as a result of vasodilation caused by lung expansion, increased PaO2, and reduced PaCO2. The elastic forces of the ribs and chest wall decrease pulmonary interstitial pressure, further enhancing blood flow through pulmonary capillaries. Increased venous return from the lungs raises left atrial pressure, thus reducing the pressure differential between left and right atria; this effect contributes to the functional closure of the foramen ovale.

As pulmonary blood flow is established, venous return from the lungs increases, raising left atrial pressure. Air breathing increases the PaO2, which constricts the umbilical arteries. Placental blood flow is reduced or stops, reducing blood return to the right atrium. Thus, right atrial pressure decreases while left atrial pressure increases; as a result, the 2 fetal components of the interatrial septum (septum primum and septum secundum) are pushed together, stopping flow through the foramen ovale. In most people, the 2 septa eventually fuse and the foramen ovale ceases to exist. However, in 25% of adults, the foramen ovale may remain patent with minimal or no residual shunting (1).

Soon after birth, systemic resistance becomes higher than pulmonary resistance, a reversal from the fetal state. Therefore, the direction of blood flow through the patent ductus arteriosus reverses, creating left-to-right shunting of blood (called transitional circulation). This state lasts from moments after birth (when the pulmonary blood flow increases and functional closure of the foramen ovale occurs) until about 24 to 72 hours of age, when the ductus arteriosus constricts. Blood entering the ductus and its vasa vasorum from the aorta has a high PO2, which, along with alterations in prostaglandin metabolism, leads to constriction and closure of the ductus arteriosus. Once the ductus arteriosus closes, an adult-type circulation exists. The 2 ventricles now pump in series, and there are no major shunts between the pulmonary and systemic circulations.

During the days immediately after birth, a stressed neonate may revert to a fetal-type circulation. Asphyxia with hypoxia and hypercarbia causes the pulmonary arterioles to constrict and the ductus arteriosus to dilate, reversing the processes described previously and resulting in right-to-left shunting through the now-patent ductus arteriosus, the reopened foramen ovale, or both. Consequently, the neonate becomes severely hypoxemic, a condition called persistent pulmonary hypertension or persistent fetal circulation (although there is no umbilical circulation). The goal of treatment is to reverse the conditions that caused pulmonary vasoconstriction.

1. 1. Koutroulou I, Tsivgoulis G, Tsalikakis D, et al: Epidemiology of Patent Foramen Ovale in General Population and in Stroke Patients: A Narrative Review. Front Neurol 11:281, 2020. Published 2020 Apr 28. doi:10.3389/fneur.2020.00281

• Varying amounts of deoxygenated venous blood are shunted to the left heart (right-to-left shunt), reducing systemic arterial oxygen saturation.

If there is > 5 g/dL (> 50 g/L) of deoxygenated hemoglobin, cyanosis results. Complications of persistent cyanosis include polycythemia, clubbing, thromboembolism (including stroke), bleeding disorders, brain abscess, and hyperuricemia. Hypercyanotic spells can occur in infants with unrepaired tetralogy of Fallot or other complex congenital defects with dynamic subpulmonic stenosis and a ventricular defect.

Depending on the anomaly, pulmonary blood flow may be reduced, normal, or increased (often resulting in heart failure in addition to cyanosis), resulting in cyanosis of variable severity. Heart murmurs are variably audible and are not specific.

• Oxygenated blood from the left heart (left atrium or left ventricle) or the aorta shunts to the right heart (right atrium or right ventricle) or the pulmonary artery through an opening or communication between the 2 sides.

Immediately after birth, pulmonary vascular resistance is high and flow through this communication may be minimal or bidirectional. Within the first 24 to 48 hours of life, however, the pulmonary vascular resistance progressively falls, at which point blood will increasingly flow from left to right. The additional blood flow to the right side increases pulmonary blood flow and pulmonary artery pressure to a varying degree. The greater the increase, the more severe the symptoms; a small left-to-right shunt typically does not cause symptoms or signs.

High-pressure shunts (those at the ventricular or great artery level) become apparent several days to a few weeks after birth; low-pressure shunts (atrial septal defects) become apparent considerably later. If untreated, elevated pulmonary blood flow and pulmonary artery pressure may lead to pulmonary vascular disease and eventually Eisenmenger syndrome. Large left-to-right shunts (eg, large ventricular septal defect [VSD], patent ductus arteriosus [PDA]) cause excess pulmonary blood flow and left ventricular volume overload, which may lead to signs of heart failure and during infancy often result in failure to thrive. A large left-to-right shunt also leads to lower lung compliance and higher airway resistance. These factors increase the likelihood of hospitalization in infants with respiratory syncytial virus or other upper or lower respiratory tract infections.

• Blood flow is obstructed, causing a pressure gradient across the obstruction.

The resulting pressure overload proximal to the obstruction may cause ventricular hypertrophy and heart failure. The most obvious manifestation is a heart murmur, which results from turbulent flow through the obstructed (stenotic) point. Examples are congenital aortic stenosis, which accounts for 3 to 6% of congenital heart anomalies, and congenital pulmonic stenosis, which accounts for 8 to 12% (1, 2).

Some congenital heart anomalies (eg, bicuspid aortic valve, mild aortic stenosis) do not significantly alter hemodynamics. Other anomalies cause pressure or volume overload, sometimes causing heart failure. Heart failure occurs when cardiac output is insufficient to meet the body’s metabolic needs or when the heart cannot adequately handle venous return, causing pulmonary congestion (in left ventricular failure), edema primarily in dependent tissues and abdominal viscera (in right ventricular failure), or both. Heart failure in infants and children has many causes other than congenital heart anomalies (see table Common Causes of Heart Failure in Children).

The ductus arteriosus is a normal connection between the pulmonary artery and aorta; it is necessary for proper fetal circulation. At birth, the rise in PaO2 and decline in prostaglandin concentration cause closure of the ductus arteriosus, typically beginning within the first 10 to 15 hours of life.

Some congenital cardiac disorders are dependent on the ductus arteriosus remaining open to maintain systemic blood flow (eg, hypoplastic left heart syndrome, critical aortic stenosis, coarctation of the aorta) or pulmonary blood flow (cyanotic lesions such as pulmonary atresia or severe tetralogy of Fallot). Keeping the ductus arteriosus open with exogenous prostaglandin infusion is therefore vital in these disorders prior to definitive repair (usually surgery).

1. 1. Daubeney PEF, Rigby ML, Niwa K, Gatzoulis MA (eds): Pediatric Heart Disease: A Practical Guide. Wiley-Blackwell 2012 .

2. 2. Hoffman JI, Kaplan S: The incidence of congenital heart disease. J Am Coll Cardiol 39(12):1890-1900, 2002. doi:10.1016/s0735-1097(02)01886-7

Most left-to-right shunts and obstructive lesions cause systolic murmurs. Systolic murmurs and thrills are most prominent at the surface closest to their point of origin, making location diagnostically helpful. Increased flow across the pulmonary or aortic valve causes a midsystolic crescendo-decrescendo (ejection systolic) murmur. Regurgitant flow through an atrioventricular valve or flow across a ventricular septal defect causes a holosystolic (pansystolic) murmur that obscures the first heart sound (S1) as its intensity increases.

Patent ductus arteriosus typically causes a continuous murmur that is uninterrupted by the S2 because blood flows through the ductus during systole and diastole. This murmur is 2-toned, having a more pronounced sound during systole (when driven by higher pressure) than during diastole.

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Central cyanosis is characterized by bluish discoloration of the lips and tongue and/or nail beds; it occurs when there is an increase in deoxygenated hemoglobin (at least 5 g/dL [50 g/L]) and implies a low blood oxygen level (usually oxygen saturation < 85%). Perioral cyanosis and acrocyanosis (cyanosis of the hands and feet) without lip or nail bed cyanosis is caused by peripheral vasoconstriction rather than hypoxemia and is a common, normal finding in neonates. Older children with longstanding cyanosis often develop clubbing of the nail beds.

In infants, symptoms or signs of heart failure include

• Tachycardia

• Tachypnea

• Dyspnea during feeding

• Diaphoresis, especially during feeding

• Restlessness, irritability

• Hepatomegaly

• Failure to thrive

Dyspnea during feeding causes inadequate intake and poor growth, which may be worsened by increased metabolic demands in heart failure and frequent respiratory tract infections. In contrast to adults and older children, most infants do not have distended neck veins and dependent edema; however, they occasionally have edema in the periorbital area. Hepatomegaly is a particularly prominent feature of heart failure in infants because of the distensibility of the liver capsule at this age. Findings in older children with heart failure are similar to those in adults.

In neonates, circulatory shock may be the first manifestation of certain anomalies (eg, hypoplastic left heart syndrome, critical aortic stenosis, interrupted aortic arch, coarctation of the aorta). Neonates appear extremely ill with pale or cyanotic mucous membranes, cold extremities, diminished pulses, low blood pressure, and reduced response to stimuli.

Chest pain in children is usually noncardiac. In infants, chest pain may be manifested by unexplained marked irritability, particularly during or after feeding, and can be caused by anomalous origin of the left coronary artery from the pulmonary artery. In older children and adolescents, chest pain due to a cardiac etiology is usually associated with exertion and may be caused by a coronary anomaly, pericarditis, myocarditis, hypertrophic cardiomyopathy, or severe aortic stenosis.

Syncope, typically without warning symptoms and often in association with exertion, may occur with certain anomalies including cardiomyopathy (hypertrophic or dilated), anomalous origin of a coronary artery, or inherited arrhythmia syndromes (eg, long QT syndrome, catecholaminergic polymorphic ventricular tachycardia [CPVT], Brugada syndrome). High school–age athletes are most commonly affected.

1. 1. Martin GR, Ewer AK, Gaviglio A, et al: Updated Strategies for Pulse Oximetry Screening for Critical Congenital Heart Disease. Pediatrics 146(1):e20191650, 2020. doi:10.1542/peds.2019-1650

Acute, severe heart failure or cyanosis during the first week of life is a medical emergency. Secure vascular access should be established, preferably via an umbilical venous catheter.

When critical congenital heart disease is suspected or confirmed, an IV infusion of prostaglandin E1 should be started at 0.05 to 0.1 mcg/kg/minute. Keeping the ductus open is important because most cardiac lesions manifesting at this age are ductal-dependent for either systemic blood flow (eg, hypoplastic left heart syndrome, critical aortic stenosis, coarctation of the aorta) or pulmonary blood flow (cyanotic lesions such as critical pulmonary stenosis, pulmonary atresia or severe tetralogy of Fallot).

Mechanical ventilation is often necessary in critically ill neonates. Supplemental oxygen should be given judiciously or even withheld because supplemental oxygen can decrease pulmonary vascular resistance, which is harmful to infants with certain defects (eg, hypoplastic left heart syndrome).

Other therapies for neonatal heart failure include diuretics, inotropic drugs, and drugs to reduce afterload. The diuretic furosemide is given as an initial bolus of 1 mg/kg IV and titrated based on urine output. Infusions of the inotropes dopamine or dobutamine can support blood pressure but have the disadvantage of increasing heart rate and afterload, thus increasing myocardial oxygen consumption. They are infrequently used in infants with congenital heart disease. Milrinone, frequently used in postoperative patients with congenital heart disease, is both a positive inotrope and a vasodilator. Dopamine, dobutamine, and milrinone all have the potential to increase the risk of arrhythmias. Nitroprusside, a pure vasodilator, may be used for postoperative hypertension. It is started at 0.3 to 0.5 mcg/kg/minute and titrated to desired effect (usual maintenance dose is about 3 mcg/kg/minute).

Therapies often include a diuretic (eg, furosemide 0.5 to 1 mg/kg IV or 1 to 3 mg/kg orally every 8 to 24 hours, titrated upward as needed) and an ACE inhibitor (eg, captopril 0.1 to 0.3 mg/kg orally 3 times a day). A potassium-sparing diuretic (eg, spironolactone 1 mg/kg orally once or twice a day, titrated up to 2 mg/kg/dose if needed) may be useful, particularly if high-dose furosemide is required. Beta-blockers (eg, carvedilol, metoprolol) are often added for children with chronic congestive heart failure. Newer medications used in adults for heart failure, such as sacubitril/valsartan and sodium-glucose cotransporter-2 (SGLT-2) inhibitors, may be useful, but data are limited in the pediatric population (1).

Digoxin is used less often than in the past but may still have a role in children with heart failure who have large left-to-right shunts and in certain postoperative patients with congenital heart disease (dose varies by age; see table Oral Digoxin Dosage in Children). Notably, digoxin has been shown to reduce mortality in single-ventricle patients after the Norwood procedure and before the second stage surgery (2). Use of digoxin as a front-line drug in the treatment of neonatal supraventricular tachycardia has declined because it results in higher mortality than treatment with propranolol (3). However, if Wolff-Parkinson-White syndrome is not present, it may be a useful as a primary agent if propranolol is ineffective or as a second agent combined with propranolol or other antiarrhythmic drugs.

Supplemental oxygen may lessen hypoxemia and alleviate respiratory distress in heart failure; when possible, fractional inspired oxygen (FIO2) should be kept < 40% to minimize the risk of pulmonary epithelial damage. Supplemental oxygen must be used with caution, if at all, in patients with left-to-right shunt lesions or left heart obstructive disease because it may exacerbate pulmonary overcirculation.

In general, a healthy diet, including salt restriction, is recommended, although dietary modifications may be needed depending on the specific disorder and manifestations. Heart failure increases metabolic demands and the associated dyspnea makes feeding more difficult. In infants with critical congenital heart disease, particularly those with left heart obstructive lesions, feedings may be withheld to minimize the risk of necrotizing enterocolitis. In infants with heart failure due to left-to-right-shunt lesions, enhanced caloric content feedings are recommended; these feedings increase calories supplied and do so with less risk of volume overload. Some children require tube feedings to maintain growth. If these measures do not result in weight gain, surgical repair of the anomaly is indicated.

Guidelines of the American Heart Association for prevention of endocarditis (4) state that antibiotic prophylaxis is required for children with congenital heart disease who have the following:

• Unrepaired cyanotic congenital heart disease (including children with palliative shunts and conduits)

• Completely repaired congenital heart disease during the first 6 months after surgery if prosthetic material or a device was used

• Repaired congenital heart disease with residual defects at or adjacent to the site of a prosthetic patch or prosthetic device

• Mechanical or bioprosthetic valve

• Previous episode of endocarditis

1. 1. Loss KL, Shaddy RE, Kantor PF: Recent and Upcoming Drug Therapies for Pediatric Heart Failure. Front Pediatr 9:681224, 2021. Published 2021 Nov 11. doi:10.3389/fped.2021.681224

2. 2.  Oster ME, Kelleman M, McCracken C, et al: Association of digoxin with interstage mortality: Results from the Pediatric Heart Network Single Ventricle Reconstruction Trial Public Use Dataset. J Am Heart Assoc 5(1): e002566., 2016.

3. 3. Bolin EH, Lang SM, Tang X, et al: Propranolol versus digoxin in the neonate for supraventricular tachycardia (from the Pediatric Health Information System). Am J Cardiol 119(10): 1605–1610, 2017.

4. 4. Baltimore RS, Gewitz M, Baddour LM, et al: Infective Endocarditis in Childhood: 2015 Update: A Scientific Statement From the American Heart Association. Circulation 132(15):1487–1515, 2015. doi:10.1161/CIR.0000000000000298