Risk factors for VSD

There are a variety of genetic and environmental factors predisposing to VSD. These are summarised in Table 2.

Table 2. Outline of the genetic and environmental factors attributing to VSD.

The majority of cases are attributed to multifactorial causes with Trisomy 21 being the commonest genetic association. VSDs commonly present with other septal defects, particularly ASDs in cases of genetic septal defects. Alcohol and illicit drug use is associated with septal malformation, thus, predisposing to VSDs. This may be explained by the effect of the teratogen on outflow tract formation and migration of neural crest cells resulting in a malformed cardiac septum. Sands et al ^{Reference Sands, Casey, Craig, Dornan, Rogers and Mulholland17} conducted a study to assess the incidence of VSDs in “low-risk” neonates, and to identify risk factors. The study also found a gender association, with girls having a higher incidence of VSDs (p=0.004) than boys in a population of 173 “low risk” infants. ^{Reference Sands, Casey, Craig, Dornan, Rogers and Mulholland17}

Diagnosing VSD

Congenital heart defects are predominantly diagnosed in utero using foetal ultrasonography. However, there is a risk of clinically significant defects being missed on an initial investigation, which can have implications on the timing of treatment initiation. This is evidenced by Van Nisselroojj et al who found that many congenital heart defects are still missed in prenatal screening programmes. ^{Reference Nisselrooij, Teunissen and Clur18} It was found that the major reason for this was the inadequate quality of the second-trimester standard anomaly scans used in the missed group. In 49% of the missed cases, inadequate imaging was the main cause which raised the lack of detection of congenital heart defects. ^{Reference Nisselrooij, Teunissen and Clur18} This study concluded that congenital heart defects were being missed due to poor adaptation skills which caused poor quality SAS. ^{Reference Nisselrooij, Teunissen and Clur18} Missed congenital heart defects can have grave implications on the infants’ health and delay the timing of treatment initiation. However, if left till late, missed congenital heart defects can result in severe morbidity or death.

A multicentre prospective cohort study was conducted in 2017 by Chu et al ^{Reference Chu, Yan, Ren, Li and Gui13} which evaluated the effectiveness of foetal echocardiography in the prenatal diagnosis of congenital heart defects. Women in the first trimester of pregnancy were recruited for the study; those eligible were given detailed fetal echocardiography during the second trimester of pregnancy (18–28 weeks). A total of 10,259 pregnant women were included in the study, split into high and low-risk groups. The study found that fetal echocardiography was highly sensitive for detecting major congenital heart defects, but was less sensitive in diagnosing minor defects. When compared with muscular VSDs, perimembranous VSDs had greater sensitivities, but this was still markedly lower than major congenital heart defects such as Hypoplastic Left Heart Syndrome. ^{Reference Chu, Yan, Ren, Li and Gui13} It was concluded that the utilisation of fetal echocardiography would be beneficial in the detection of major defects and would, therefore, aid parental counselling. ^{Reference Chu, Yan, Ren, Li and Gui13} However, there was still a risk of delayed diagnoses due to the reduced sensitivity of echocardiography in detecting minor defects.

Early measurement of pulse oximetry can be utilised as an option to promote early detection of congenital heart defects including VSD. ^{Reference Stockman19} The PulseOx study ^{Reference Ewer, Middleton and Furmston12} was a prospective test accuracy study aiming to assess the accuracy of pulse oximetry as a screening tool for congenital heart defects such as VSD. The study analysed all asymptomatic babies born at six maternity units in the United Kingdom (20,055 babies in total), who were screened with pulse oximetry prior to discharge. Subsequently, infants not achieving predetermined oxygen saturations were given echocardiography after clinical examination. ^{Reference Ewer, Middleton and Furmston12} The results of the study found that 50% of the babies with critical congenital heart defects had already been suspected at the antenatal screening, but 36% of those with major congenital heart defects (critical and serious) had been detected at screening. Six babies with critical congenital heart defects were falsely negative on pulse oximetry, and a further 21 babies with normal pulse oximetry findings had serious congenital heart defects such as VSD. The overall sensitivity of pulse oximetry was found to be 76% for critical cases, and 49% for serious cases. ^{Reference Ewer, Middleton and Furmston12} The study, therefore, concluded that pulse oximetry was a “safe, feasible test” that aids in the screening process by helping to detect cases of critical CHD that aren’t detected by ultrasound. ^{Reference Ewer, Middleton and Furmston12} These findings are further supported by another pulse oximetry study by Xiao-jing Hu et al who tested the use of pulse oximetry on 4128 newborn infants without a prenatal diagnosis of congenital heart defects. ^{Reference Hu, Zhao and Ma20} Of these infants, 19 were found to have critical congenital heart defects. ^{Reference Hu, Zhao and Ma20} However, if pulse oximetry was not used then there would have been seven missed cases of congenital heart defects. ^{Reference Hu, Zhao and Ma20} Therefore, this study concluded that incorporating pulse oximetry into the screening process for congenital heart defects was vital in preventing delayed cases which would have been detrimental for those infants’ health.

Indications for repair of VSD

Indications for surgical intervention in VSD vary depending on the characteristics of the defect, such as the size and anatomical type. Small defects don’t require surgical closure as they usually undergo spontaneous closure. However, intervention may be required if the defect is moderately sized. Indications for closure in these cases include failure to thrive and poor development, significant enlargement of the left atrium or ventricle and/or elevated pulmonary arterial pressure, or a pulmonary–systemic flow ratio of greater than 2:1. ^{Reference Rao21} Another indication for surgical repair is the development of significant aortic regurgitation due to prolapse of one of the aortic cusps. If congestive heart failure is present, it should be treated promptly. If the defect is large, a surgical closure is indicated in cases where systolic pressures in the right ventricle and pulmonary artery are close to left ventricular and aortic pressures. ^{Reference Rao21}

Open versus minimally invasive approaches to VSD closure

Traditionally, patients with VSD requiring treatment underwent open surgical intervention, however with advances in medical technology, there are now minimally invasive options available. Liu H et al conducted an open-label randomised controlled trial comparing the traditional open surgical approach to the new minimally invasive periventricular approach. ^{Reference Liu, Lu and Zhou10} This study found that periventricular closure of ventricular septal defects was associated with a decreased rate of haemodynamic compromise, disorders of respiratory mechanics and cardiomyocyte viability, and tissue perfusion when compared with surgical closure. ^{Reference Liu, Lu and Zhou10} However, it was also found that open surgical approaches were associated with a greater degree of complete defect closure than the periventricular technique. Continuous data were presented as means and standard deviations and compared by t-test by adhering to the normal Gaussian distribution. ^{Reference Liu, Lu and Zhou10}

In 2014, Yang J et al randomised 229 infants into two treatment arms, one receiving open surgical closure and the other undergoing a minimally invasive transcatheter approach. ^{Reference Yang, Yang and Yu11} The infants were followed up for 2 years afterwards and a record was made of any major/minor adverse events, and laboratory testing was carried out measuring levels of CK-MB, ALT, BUN, and cTnI. Also, an echocardiogram was conducted 3 days after surgery to measure the degree of VSD closure. The results of the study found that neither the transcatheter or surgical procedures were associated with mortality or major adverse effects. However, there were 32 minor adverse effects in the surgical group and 7 in the transcatheter group (32.3% versus 6.9%). Fisher’s exact test was used to establish statistical significance, and there was a significant difference in minor adverse events found (p < 0.001). ^{Reference Yang, Yang and Yu11} The study concluded that the transcatheter approach has a lower incidence of injury to the myocardium and is associated with a faster recovery and shorter hospital stay (Table 3).

Table 3. Comparative outcomes of studies reporting on minimally invasive versus open repair of ventricular septal defect (VSD).