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C: After collaterals have enlarged buy dapoxetine online now erectile dysfunction age graph, there is high flow in the enlarged right coronary artery and the collaterals and significant retrograde flow into the pulmonary artery generic dapoxetine 30mg with mastercard erectile dysfunction doctors huntsville al. Arrows indicate direction and approximate magnitude of flow in the right and left coronary arteries and the collaterals between them. Pathology This anomaly is usually isolated but its presentation has been associated with, and is complicated by patent ductus arteriosus (17,33), ventricular septal defect, tetralogy of Fallot, or coarctation of the aorta (33). If there is pulmonary hypertension, as with a large ventricular septal defect, left ventricular perfusion may be adequate to prevent ischemia. Under these circumstances, closure of the defect with a decrease in pulmonary arterial pressure is catastrophic. The right coronary artery is greatly dilated, and large collaterals may be visible on the surface of the heart. The left coronary artery is seen entering the main pulmonary artery, usually in the left pulmonary sinus, but rarely enters a branch pulmonary artery. In infancy, the heart is large, the left ventricle and atrium in particular being dilated and hypertrophied. The anterolateral papillary muscle may be atrophic and scarred, and the chordae attached to it may be shortened. In some studies, the posteromedial papillary muscle has been similarly affected (33). There may be diffuse endocardial fibroelastosis of the left ventricle, and the anterior mitral valve leaflet is often thickened. Thinning and scarring of the anterolateral left ventricular wall and apex owing to infarction are noted, and there are often mural thrombi. The heart is usually enlarged, but not as much as in infants, and there is usually no endocardial fibroelastosis. However, there is usually scarring and calcification of the anterolateral papillary muscle and occasionally even of the adjacent left ventricle (18,34). The infant appeared at first to be in obvious distress, as indicated by short expiratory grunts, followed immediately by marked pallor and cold sweat with a general appearance of severe shock. Occasionally, with unusually severe attacks, there appeared to be a transient loss of consciousness. The eructation of gas at times seemed to relieve the discomfort and to shorten the duration of the attack which usually lasted from 5 to 10 minutes, and following which the infant might proceed to nurse without difficulty and remain free of symptoms for several days… It seems probable that in this infant the curious attacks of paroxysmal discomfort… were those of angina pectoris. If this is true, it represents the earliest age at which this condition has been recorded. A few children have severe difficulties in infancy and then gradually improve until they are asymptomatic. Older children and adults may be asymptomatic or may have dyspnea, syncope, or angina pectoris on effort. However, typical myocardial infarctions or congestive heart failure is rare in adults. In infants, the heart is usually enlarged, the left ventricle being the predominant ventricle affected. However, there may be right ventricular enlargement and a loud pulmonary component of the second heart sound if left ventricular failure has caused considerable pulmonary hypertension. The first heart sound may be soft or absent (if there is mitral regurgitation), and apical gallop rhythms are common. There may be no murmurs, or the murmur of mitral regurgitation, or at times a soft continuous murmur at the upper left sternal border that is similar to the murmur of a small patent ductus arteriosus, which is due to the continuous flow from the anomalous coronary artery into the pulmonary artery. There also may be abnormal R waves or R- wave progression in the left precordial leads. Although this pattern is not pathognomonic for this anomaly (it is seen in myocardial infarcts from other causes or occasionally in cardiomyopathies), if found, the diagnosis of this anomaly should be considered and evaluated by other means. Even in asymptomatic adults, the resting electrocardiogram is abnormal, and abnormal ischemic responses occur with exercise (34). Noninvasive Imaging On the chest film in affected infants there is marked cardiomegaly, predominantly of the left atrium and ventricle, and evidence of pulmonary edema. These features are similar to those of many forms of cardiomyopathy, with which this anomaly is often confused. Nuclear myocardial perfusion imaging is quite sensitive, showing reduced uptake in the anterolateral ischemic region. However, this finding is not specific because it has been seen in cardiomyopathies as well. Echocardiography with Doppler color flow mapping has replaced cardiac catheterization as the standard method of diagnosis (36). The improved resolution of current echocardiographic equipment often allows the abnormal aortic origin of the left coronary artery to be seen. Color Doppler interrogation shows that flow passes from the coronary artery into the pulmonary artery. Therefore, even if the origin of the coronary artery to the aorta is not well defined by two-dimensional imaging, the presence of diastolic flow in the pulmonary artery will be informative. An enlarged right coronary artery should also raise the suspicion of the diagnosis. Echocardiography also will show the size and function of the cardiac chambers, particularly the left ventricle, as well as regional left ventricular wall motion abnormalities and mitral regurgitation. There may be increased echogenicity of the papillary muscle and adjacent endocardium due to fibrosis and fibroelastosis. Computed tomography scans have shown their high resolution in defining coronary artery anatomy and origination in most patients older than infancy. The main advantage of this technique is rapid acquisition times and high resolution. There remains a degree of radiation exposure with this technique, but its ability to define coronary artery abnormalities is excellent (see Fig. Cardiac Catheterization and Angiography Although previously cardiac catheterization and angiography were commonly used in the diagnosis of congenital coronary abnormalities, currently they are used only if the results of noninvasive imaging are indeterminate. In symptomatic infants, diagnostic cardiac catheterization demonstrates a low cardiac output and high filling pressures, and usually some degree of pulmonary hypertension. In asymptomatic older patients, output and pressures are usually normal except for a slight increase in left ventricular end-diastolic pressure. There may be a left-to-right shunt at the pulmonary arterial level, but because the shunt may be small, its absence does not rule out the diagnosis. Aortic root angiography will show the dilated right coronary artery and, if there are large collaterals, will show filling of the left coronary artery and passage of contrast material from the left coronary to the main pulmonary artery. Attempts at selective left coronary artery angiography will only show filling of the left sinus of Valsalva without opacification of the left coronary artery. Usually selective right coronary artery angiography is diagnostic in showing filing of the left coronary artery via collaterals, with backfilling to its pulmonary ostia (see Video 32.
Pregnancy in women with a systemic right ventricle after surgically and congenitally corrected transposition of the great arteries purchase cheap dapoxetine on line ramipril erectile dysfunction treatment. Pregnancy and long-term cardiovascular outcomes in women with congenitally corrected transposition of the great arteries buy 30mg dapoxetine impotence hernia. There is no known racial or gender predilection, and no associated genetic defect has been identified. As with much of congenital heart disease, the physiology and treatment of these defects are derived from the embryology and morphology. With the exception of truncus arteriosus, which occurs due to failure of septation, other conotruncal defects are essentially rotational defects. The variability among the individual lesions is best understood in terms of the spectrum of development of the conal septum, which determines the relative position of the two semilunar valves to the ventricles. In the normal heart, the pulmonary valve sits up on the conus, a circular tube of muscle, and is positioned anteriorly and superiorly (17). In contrast, the aortic, mitral, and tricuspid valves are all attached to the central fibrous body of the heart. The conal muscle beneath the aortic valve largely resorbs, leaving the aorta positioned inferiorly and posteriorly (Fig. In conotruncal defects, there is a spectrum between hearts in which no conus exists beneath the aorta, as seen in tetralogy of Fallot, and no conus exists under the pulmonary valve, as with transposition of the great arteries (Fig. There is a near- normal length of conus beneath the pulmonary valve and minimal conus beneath the aortic valve. Consequently, there is no aorto-mitral continuity, and the pulmonary valve is anterior and superior. In the middle is a type which has equal bilateral conus, such that the great arteries are side by side, with neither vessel tucked in posteriorly. These variations are more ambiguous both anatomically and physiologically and should be approached with an individualized management plan. In the fetus, there is a circular tube of muscle, the conus, beneath each great artery. The distribution of conal muscle is equal beneath the aorta and the pulmonary artery. In the normal heart, the pulmonary valve sits up on the conus, and is positioned anteriorly and superiorly. The conal muscle beneath the aortic valve largely resorbs, leaving the aorta positioned inferiorly and posteriorly. The more conal muscle present beneath a semilunar valve, the more that valve is pushed superiorly and anteriorly. Aorta is pushed anteriorly and superiorly, resulting in rightward positioning of the aorta relative to the pulmonary artery. However, coronary arterial anomalies are of particular importance, because they may alter considerations for surgical repair due to their effect on feasibility of conduit placement or coronary arterial transfer (23) (Fig. Likewise, associated aortic arch coarctation, hypoplasia, or interruption—also found in about 10% of patients—significantly increase the complexity of surgical repair when present (24,25). Even within the same subtype, there can be substantial variability in the clinical presentation. Historically, cardiac catheterization with angiography and hemodynamic assessment were used routinely for diagnostic evaluation. Currently, however, transthoracic echocardiography can identify all of the essential anatomic features in most cases, and the echocardiogram along with bedside pulse oximetry provides definitive diagnosis of the pathophysiology noninvasively (26). For patients with complex aortic arch anatomy, angiography may also be needed (27,28). In a minority of patients, for example those for whom the technical feasibility of a two-ventricular repair is uncertain, cardiac catheterization is used to define pulmonary vascular resistance to determine suitability for a Fontan operation. Hemodynamic assessment via cardiac catheterization may also be necessary for another small subset of patients in whom the effects of intracardiac streaming are variable and less apparent (10). Tetralogy Type The most common variant is the “tetralogy of Fallot type,” with most of the conus under the pulmonary valve and minimal conal septum under the aorta (see Fig. The pulmonary valve is positioned anteriorly and superiorly, and the aorta overrides the interventricular septum. Typically there is progressive, dynamic obstruction to pulmonary blood flow at the subvalvar level, leading to oxygen saturations between 80% and 90% at baseline, with further desaturation during agitation. Cyanosis may not be present for several weeks, but after that time, it gradually worsens. The chest radiograph demonstrates normal to mildly diminished pulmonary vascular markings. The electrocardiogram is notable for right axis deviation and a right ventricular hypertrophy pattern, with rR′, qR, or rsR′ pattern; these findings are not, however, sufficiently specific to be diagnostic. There is no flow disturbance through the ventricular septal defect, which is large and not pressure restrictive (Video 49. This image demonstrates both great arteries arising from the right ventricle, with conal septum separating the aorta and the pulmonary artery. C: 3-D echocardiogram, with subaortic ventricular septal defect (asterisk) and marked subpulmonary and pulmonary valve stenosis (Video 49. The ventricular septal defect is bounded by the underside of the aortic valve and cradled inferiorly in the arms of the septomarginal trabeculations. B: This sagittal image demonstrates prominent conal muscle beneath the pulmonary valve. The degree of obstruction at the subvalvar level determines the degree of cyanosis. Surgical repair or palliation with a modified Blalock–Thomas–Taussig shunt as a neonate is indicated when there is severe limitation to pulmonary blood flow. In most patients, however, surgery is performed electively between 2 and 4 months of age before the infant becomes excessively cyanotic or develops hypercyanotic spells. In this type, the aorta is pushed anteriorly and superiorly, resulting in rightward positioning of the aorta relative to the pulmonary artery. Thus, there is transposition physiology with a pulmonary arterial oxygen saturation that is higher than the aortic oxygen saturation. Relatively large subaortic conus (small arrow) separates the aorta and pulmonary artery (Video 49. B: Subcostal coronal view: Aorta and pulmonary artery both arise from the right ventricle with the aorta rightward and slightly anterior (Video 49. Large subaortic conus separates the aorta and pulmonary artery with narrowing of the egress from the left ventricle due to the conal septum and tricuspid valve chordal attachments. There is tissue beneath the pulmonary valve (small arrow); due to this subvalvar obstruction, the pulmonary artery is relatively small compared to the aorta. Due to the subaortic obstruction, the aortic valve and ascending aorta are relatively hypoplastic. Ventricular septal defect demarcated by arrows at the crest of the interventricular septum and at the small rim of conal septum beneath the pulmonary valve.
The Total Maturation Scoring System developed by Childs to measure brain maturation in premature infants incorporates information related to myelination buy dapoxetine australia impotence 101, cortical infolding order dapoxetine canada erectile dysfunction treatment after prostatectomy, glial cell migration bands, and the presence of germinal matrix tissue (49). Moreover, preoperative cerebral lactate peaks were elevated in more than half of infants evaluated by magnetic resonance spectroscopy. In the early postoperative period, 48% of infants had new periventricular leukoencephalopathy, 19% had new infarcts, and 33% had new parenchymal hemorrhage. However, cerebral atrophy was detected in two, old infarct in one, and new infarct in one subject. Lower scores on developmental assessments were not associated with the presence of new postoperative white matter injury but did correlate with preoperative white matter injury and brain immaturity (54). Changes in central nervous system structure may underlie neurocognitive abnormalities in children with congenital heart disease. For example, worse performance in math problem solving and numerical operations was correlated with reduced left parietal fractional anisotropy. In a mixed group of congenital heart disease adolescents, compared to controls, brain volume was reduced, and the extent of brain volume reduction was significantly associated with scores on tests of cognition, executive function, and motor function (56). Perioperative Risk Factors Prospective studies of central nervous system protection and injury have mainly focused on risk factors related to cardiac surgery and the perioperative period. The intense attention to perioperative risk factors is likely related to the ability of investigators to study the brain during this high-risk period, which includes planned brain ischemia–reperfusion injury with use of hypothermic cardiopulmonary bypass and total circulatory arrest techniques. Furthermore, perioperative management strategies can be tested in randomized clinical trials. Perioperative Monitoring Approaches As investigators have sought to optimize neurodevelopmental outcomes by modifying surgical and medical perioperative approaches, one limiting factor has been difficulty in identifying early predictive markers of longer- term developmental outcomes. However, some centers have adopted perioperative monitoring strategies that include continuous electroencephalogram, near- infrared spectroscopy, and/or transcranial Doppler ultrasound (51,57,58). Clinical adoption of these monitoring techniques has outpaced establishment of definitive evidence for their clinical benefit. Further study of this technique, other perioperative monitoring approaches and additional potential early markers are needed to better understand how late outcomes can be predicted in newborns and infants undergoing cardiac surgery. Nonetheless, a great deal has been learned since the 1990s related to perioperative risk factors of central nervous system insults for children with congenital heart disease. Intraoperative Support Techniques Repair of congenital heart disease commonly requires the use of cardiopulmonary bypass, in which blood is exposed to artificial surfaces. Furthermore, cardiopulmonary bypass is accompanied by risks of gaseous and particulate embolism, macroemboli, and hypoperfusion resulting in diffuse ischemia/reperfusion injury (61). Its effects are derived, in part, from a reduction in metabolic activity reflected in reduced oxygen consumption. Additional mechanisms of hypothermic protection of the brain and other organs during ischemia include preservation of intracellular stores of high-energy phosphates and of high intracellular pH, as well as protection against reperfusion injury including the no-reflow phenomenon, calcium influx, and free radical damage (65). Circulatory arrest has been widely used since the 1960s in centers with expertise in infant open cardiac surgery. This technique has advantages for the surgeon of absence of perfusion cannulae and of blood from the operative field, though it may increase the risk for neurologic insult. When evaluated as a continuous variable, a longer duration of total circulatory arrest has been associated with increased risk of seizures, choreoathetosis, release of brain isoenzymes, and developmental delay (71,72,73,74,75,76,77,78,79,80,81) though in some studies, the duration of circulatory arrest has not been a significant predictor of outcome (68,82). The absence of an effect may be related, in part, to a narrow range of circulatory arrest times, small sample sizes, or overwhelming effects of other risk factors for adverse outcome, such as underlying genetic abnormalities or severe hemodynamic instability in the preoperative or postoperative period. A universally “safe” duration of total circulatory arrest cannot be determined, however, because of its potential interaction with patient factors, such as age and a host of other perfusion variables that affect outcomes, including the depth of hypothermia (84), the rate and duration of core cooling (85), acid–base management during core cooling (86,87), and the degree of hemodilution (88). Hemodilution during hypothermic cardiopulmonary bypass has also been studied with respect to its effects on brain injury during infant heart surgery. At the profoundly low temperatures (15° to 18°C) used during infant and neonatal cardiac surgery, hypothermia increases the viscosity of blood and red blood cell aggregation (91), potentially increasing the risk of microvascular occlusion. Hemodilution has been used to counter these risks (92) and has been shown to increase cerebral blood flow (93), but could reduce the oxygen-carrying capacity of blood. Furthermore, because hypothermia induces a leftward shift of oxyhemoglobin dissociation, hemodilution has the potential to limit oxygen delivery to the central nervous system (92). A subsequent trial showed no differences in neurodevelopmental outcome at 1 year with hemodilution within the range of 25% to 35% (94). It is likely that factors such as hematocrit, temperature, pH strategy, and duration of circulatory arrest or very reduced flow interact in their effects on the central nervous system (95,96). For example, the reduced oxygen- carrying capacity of a low hematocrit during cardiopulmonary bypass can be compensated for by the use of the pH-stat strategy, by increasing flow rate, reducing the duration of circulatory arrest, or reducing temperature. Preoperative Factors and Host Susceptibility Host susceptibility is likely to affect the response of the central nervous system to cardiopulmonary bypass and perioperative events (97). Preoperative patient characteristics such as low Apgar scores at 5 minutes, younger gestational age, lower birth weight, and other attributes have been found to be independent risk factors for adverse neurodevelopmental outcomes (89,98). Furthermore, the response to cardiac surgery may be mediated by genetic polymorphisms in the pathways affected by exposure to cardiopulmonary bypass, including inflammation, thrombosis, vascular reactivity, and oxidative stress (100). Indeed, it is most likely that the effects of bypass on individual patients are mediated by many different genetic polymorphisms in the domains of inflammation, coagulation, and response to ischemia/reperfusion injury. The influence of genetic polymorphisms on postoperative morbidity has been extensively studied among adults undergoing open heart surgery (101,102,103,104,105). For example, postoperative bleeding is more common among adults with polymorphisms in genes coding for coagulation proteins and platelet glycoproteins (105), while postoperative thrombotic complications have been associated with gene polymorphisms in fibrinogen and angiotensin-converting enzyme (106). Interestingly, this finding underscores that children and adults may differ with respect to the effects of particular genotypes. Postoperative Factors Various risk factors for brain injury occur in the postoperative period. A low cardiac output syndrome is common in the first 24 to 48 hours following repair of complex congenital heart disease (115,116). Hemodynamic instability and low cardiac output syndrome may be especially damaging to the vulnerable central nervous system of the neonate who has just undergone cardiac surgery using deep hypothermic cardiopulmonary bypass techniques. Hypoxic–ischemic insult related to hypothermic cardiopulmonary bypass techniques disrupts the integrity of cerebral vasoregulatory systems in the early postoperative period, and autoregulation of cerebral blood flow is impaired (117,118,119,120). Persistence of such disturbances in cerebrovascular control renders the brain vulnerable to subsequent insults, such as hypotension or hypoxia. The complexity of the postoperative course may also impact on later neurodevelopmental outcome. In the multicenter Single Ventricle Reconstruction trial, longer hospital length of stay after the Norwood procedure was also associated with worse neurodevelopment at age 14 months among infants with hypoplastic left ventricle and other single right ventricle anomalies (122). The adverse effect of longer hospitalization on neurodevelopmental outcome reflects multiple contributory factors that prolong recovery. The hormonal milieu after cardiac surgery might influence the central nervous system. For example, a sick euthyroid syndrome is common among infants and children following open heart surgery, and the degree of thyroid suppression appears to be greatest after the most complex operations (123,124,125,126,127,128,129,130,131,132).