The symptoms and physical findings of VSD strongly depends on two important factors, the size of the defect itself and the extent of the left-to-right shunt.

In the cases of small VSDs, symptoms are typically mild or even non-existent, with the infants apparently showing normal vital signs. Physical findings consist primarily in cardiac manifestations. Typical of this type of condition are the retained physiologic splitting of S2 and the harsh and holosystolic murmur, which turns out to be well-localized and loudest on the lower left stern border (LSB). The murmur is usually detected during routine examination after 4-8 weeks from birth, when pulmonary vascular resistance (PVR) begins to decrease. Because of the limited physiological effects, feeding and weight gain are usually not affected.

In the cases of moderate VSDs, infants present normal length but usually decreased weight and weight gain, which are indicative of a congestive heart failure. They also frequently show fatigue with feeding, since this requires an increase in cardiac output, revealing the possibility of exercise intolerance. This condition is usually associated with lack of adequate growth, which is due to an increased caloric requirement not met by the impaired feeding ability. The harsh and holosystolic murmur is prominent on the lower LSB, typically associated with an evident thrill and usually present in combination with a diastolic rumble in the mitral area, which in turn suggests a functional mitral stenosis as consequence of a large left-to-right shunt. Other signs include excessive sweating, as a result of an increased sympathetic tone and usually notable during feeds, and also frequent respiratory infections due to pulmonary congestion.

The symptoms in the cases of large VSDs, instead, look very much like those of the moderate VSDs, even though they are much more pronounced and severe. The only difference lies in the moment of appearance, since they begin to emerge later because of the delay in the decrease of pulmonary vascular pressure. Very common in this case are also poor weight, frequent pulmonary infections, and the harsh holosystolic murmur which always appear to be associated with diastolic rumble but much more poorly localized. Signs of congestive heart failure (CHF) are evident and include tachycardia, tachypnea, hepatomegaly, and cardiomegaly, most important to differentiate the cases of heart failure from those due to other respiratory conditions like bronchiolitis.

Usually associated with VSD is the Eisenmerger syndrome or VSD with severe pulmonary vascular disease, a condition in which the left-to-right shunt causes an increase of the blood flow circulating through the pulmonary vasculature and thus pulmonary hypertension [5]. The consequences of this particular condition are an increased pressure in the right side of the heart and the possible reversal of the shut, from left-to-right to a right-to-left. In this situation, children tend to show the symptoms seen so far, like tachypnea and cyanosis, when they are under physical exercise but not when they are at rest.

Cardiac auscultation is the typical diagnostic procedure to detect the classic holo- or pan-systolic murmur characterizing VSD, and it is generally considered to be sufficient for a conclusive diagnosis, especially in the most evident cases. The intensity of the murmur depends on the abnormal blood flow from the left to the right ventricle, because the higher this intensity is, the higher the abnormal flow itself, and thus the higher the difference in pressure between the two sides of the heart.

Cardiac catheterization is another standard procedure for the evaluation of VSD, used especially for its accuracy in measuring the ventricular pressures and the pulmonary-to-systemic flow ratio, which is extremely useful to assist the decision-making process for possible surgical procedures.

Frequently used is also echocardiography, together with chest radiography and magnetic resonance imaging, because of the fundamental information it provides regarding the location and size of the septal opening(s). This is the reason why it is typically preferred over cardiac catheterization.

Many cases of VSD are represented by small septal openings which close on their own and do not require treatment. On the other hand, in the majority of the cases (around 80%) the openings are large enough to create substantial pathophysiological effects [6] requiring some type of medical intervention, both in terms of medications and in terms of surgery.

Whatever is the case, the infants are always initially treated with medications, the most typical of which are cardiac glycosides, loop diuretics, and ACE inhibitors. Surgery, instead, is usually represented by an open-heart surgical intervention integrated with catheter-based procedures usually performed in four different situations: a) ineffectiveness of medications in treating congestive cardiac failure, b) VSD associated with pulmonic stenosis, c) large VSD associated with pulmonary hypertension, and d) VSD associated with aortic regurgitation.

One of the most commonly used devices in VSD surgery is Amplatzer ® Septal Occluder, originally designed to close openings in the atrium but now also used to close openings in the ventricular septum [7]. Current recommendations are to use it in patients with a weight of more than 8 kg, who have a subaortic rim of more than 2 mm. This is a self-expandable device made of a wire mesh in Nitinol, a particular braided metal possessing shape memory characteristics, which means it goes back to the original form even when it has been extensively stretched. Its design is characterized by two discs, separated by a central connective waist [8], which are placed on both septal sides (left and right) and allow a very high waist-to-disc ratio [9]. With this device, surgeons can close a septal opening within 24 hours from the placement [7] with a very low risk of embolism, but it can cause life-threatening erosions in around 1% of the cases due to improperly chosen sizes [10].

The prognosis for the patients depends on the VSD size. As previously said, the prognosis is excellent for children with small VSDs, who are asymptomatic and show no serious medical complication. On the other hand, prognosis varies in children with moderate to large VSDs, according to the severity of the case.

Many of these subjects show signs of a gradual decrease of the left-to-right shunt, in the age range going from 6 to 24 months, and remain in stable conditions after infancy. However, symptoms might reappear, especially if triggered by related events such as anemia, respiratory infection, and endocarditis, and can progressively deteriorate with the gradual increase of cyanosis and decrease of physical exercise capacity. If the general conditions become too grave, the patients might require a heart transplantation.

The current mortality of the surgical procedure for VSDs is less than 2%, and the risk of heart failure is low, especially after infancy.

The etiology of VSD has not been clearly defined, but experts assume it must be a multifactorial pathological event based on the interaction between hereditary predispositions and environmental elements.

The major risk factor of VSD is represented by a family history of cardiac or noncardiac defects including parents and preceding siblings. According to the epidemiological data available, the incidence in siblings with parents already affected by VSD is three time that of the general population, and this indicates the presence of underlying genetic factors regulating the hereditary transmission of the malformation. Among the environmental elements, instead, the maternal factors stand out as having a pivotal role, especially in the cases of serious conditions like maternal diabetes and alcohol consumption, which has already been associated with the occurrence of muscular VSDs [2].

The major challenge for cardiologists and geneticists will be to define the correlation between the genotype and the phenotype of this malformation, whose evaluation should be based on the search of risk factors, the accurate clinical diagnosis of cardiovascular defects, and the recognition of an appropriate family history. There are also some examples of chromosomally based syndromes associated with VSD, which include trisomy 21 (Down syndrome) [3], trisomy 18 (Edwards syndrome) and trisomy 13.

It is interesting to notice that some time VSD can also occur a few days after a myocardial infarction, as consequence of mechanical tearing suffered by the heart during the cardiovascular episode.

VSD is the most common congenital cardiac abnormality among the newborns, found in 30-60% of the cases of heart defects. According to the epidemiological data coming from the United States, it seems that VSDs can be found in 2-7% of the newborns, and this frequency appears to be strongly influenced by the patient’s residence, perhaps because of the higher number of sophisticated healthcare facilities present in urban areas. In any case, the incidence of VSD is high, as shown by an echocardiographic study that detects in every 1000 newborns from 5 to 50 cases of small restrictive muscular VSD, which usually close spontaneously within the first year of life [4]. As previously said, VSD is also the most common cardiac lesion in many chromosomal syndromes, like the already mentioned trisomy 13, trisomy 18, and trisomy 21. However, these represent just 5% of all the VSD cases.

VSD appears to be a little bit more frequent in women than in men, while there are no conclusive data regarding the race-related differences in the VSD distribution. The only exception is represented by the outlet defects, which appear to occur much more frequently in Asian population.

The basis of the VSD pathophysiology is the partial blood flow deviation from the left ventricle to the right ventricle (left-to-right shunt) taking place during systole, which causes the arterial blood to pass through the lungs, via the pulmonary veins and right atrium, and reenter the left ventricle. This communication between the systemic and pulmonary circulations brings about a series of pathophysiological consequences that can be divided into two groups: those deriving from the hemodynamic effects of the left-to-right shunt and those deriving from pulmonary hypertension.

The hemodynamic consequences of the left-to-right shunt consist in an increased left ventricle (LV) volume (also known as LV volume overload), the excessive pulmonary blood flood, and a reduced systemic cardiac output. The increased LV volume might result in LV dilatation which in time, if not treated, might lead to hypertrophy and all the vascular consequences associated with it. The excessive pulmonary blood flow raises capillary pressure resulting in an increase of the pulmonary interstitial fluid. This eventually leads to pulmonary edema, when fluids begin to accumulate in the air spaces and the parenchyma of the lungs, and in marked changes in pulmonary vasculature that might in turn be the source of other vascular diseases. The decreased cardiac output, instead, creates an inadequate organ perfusion which needs the activation of a series of compensatory mechanisms to be compensated, like increased catecholamine secretion.

Pulmonary hypertension is the consequence of the marked difference between in the systolic pressure of the left ventricle (around 120 mmHg) and of the right ventricle (around 20 mmHg), which ultimately causes the raise of the right ventricle pressure and volume.

The symptomatic consequences of the left-to-right shut largely depend on the size of the septal opening. If this is small, the normal pressure difference between the ventricles is maintained within an acceptable range and the defect remains asymptomatic. Problems emerge when the septal opening is large and the normal pressure difference between ventricles can no longer be maintained and the defect appears symptomatic. In the most serious cases, the opening(s) are so large that the pulmonary arterial pressure equals the systemic one and this reverses the blood shut. Blood begins to flow from the right ventricle to the left one, and as it bypasses the lungs it causes cyanosis, the appearance of a blue coloration on skin and mucous membranes due to low oxygenation rates. Other effects in infants include breathlessness, poor feeding, and failure to thrive due to improper growing pattern.

Since VSD is a congenital defect, no particular prevention plan can be advised. However, mothers are recommended to have a healthy pregnancy by following a series of important measures, like quitting smoke, avoiding infections or eating a balanced diet, required to prevent complications during fetus development.

Ventricular septal defect (VSD), a congenital structural abnormality, leads to a left to right shunt. In this case, the blood, instead of going straightaway to the aorta and from here to the rest of the body, flows into the right heart, getting back to the pulmonary circulation. This causes a series of turbulences in the blood flow which create the characteristic holosystolic murmur. As for the location, VSD can occur anywhere along the septum, most frequently it lies in the upper part, where the septum is thinner, the membranous septum [1], but sometime it can also be located in the lower part, the muscular septum.

In the majority of the cases VSD is asymptomatic, since the septum opening is very small and causes no significant problem in terms of oxygen levels, which always remain adequate without creating significant loss of function. Thus, there is no need of treatment and patients can live on experiencing no major health problem. On the other hand, if the septum opening is larger, VSD becomes symptomatic, causing significant complications to the circulatory system. Patients usually undergo surgery, whose main goal is to repair the defect so that the blood no longer flows from the left side to the right side of the heart.

Ventricular septal defect (VSD) is an anatomical anomaly consisting in the presence of one or more openings on the ventricular septum, the wall dividing the two ventricles, which allow arterial blood to flow from the left side to the right side of the heart. A VSD can be anywhere along the septum: most frequently it lies in the upper part, where the septum is thinner, known as “membranous septum”, but sometime it can also lie on the lower part, much thicker and muscular, known as “muscular septum”.

In the majority of the cases VSD is asymptomatic, since the septum opening is very small and causes no significant problem. If the septum opening is large enough, VSD becomes symptomatic causing significant complications for patients, that usually undergo surgery to repair the septal opening.

In addition to the classical holisystolic murmur, other examples of typical signs and symptoms of this malformation include fatigue with feeding, decreased weight and weight gain, congestive heart failure, lack of adequate growth and frequent respiratory infections due to pulmonary congestion.

Since VSD is present at birth, no particular prevention can be advised. However, mothers are recommended to have a healthy pregnancy by following a series of important measures, like quitting smoke, avoiding infections or eating a balanced diet, required to prevent complications during fetus development.

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