Biventricular Outflow Obstruction Associated With Atrioventricular Septal Defects and Patent Ductus Arteriosus: An Extremely Rare Combination

We present an extremely rare combination of biventricular outflow obstruction associated with atrioventricular septal defects and patent ductus arteriosus (PDA). Almost all the other published cases, including ours, were associated with other congenital cardiac lesions other than biventricular outflow obstruction. Most cases ended with poor outcomes. Our patient was a 55-day-old term female infant. She was managed by successful aortic balloon valvuloplasty with successful early outcome.

This article describes a case of a female infant patient who was diagnosed with biventricular outflow obstruction associated with VSD, atrial septal defects (ASD), and patent ductus arteriosus (PDA). To the best of our knowledge, this combination is unique in the medical literature. In this article, we are highlighting the importance of the accurate diagnosis of all described lesions, awareness of peculiar hemodynamic findings, and the importance of early intervention to avoid hemodynamic compromise. Failure to do so has the potential to lead to tragic outcomes [10].

Case Presentation
A 55-day-old term female infant with low birthweight (2 kg) was transferred to our tertiary cardiac center with a diagnosis of heart failure associated with a large VSD, moderate ASD, BAV, moderate PDA, and mild mitral regurgitation (MR). Upon arrival, the physical examination showed a nondysmorphic infant who was slightly tachypneic on nasal oxygen. Feeding was administered by a nasogastric tube. On cardiac examination, there was visible apical pulsation, no precordial bulge, and left parasternal thrill. On auscultation, the first and second heart sounds were normal. Grade 4/6 ejection systolic murmur was heard in the second and third left intercostal spaces, which were propagated all over the precordium.
The echocardiogram showed (Figures 1-4) a large secundum ASD (10 mm) with a left to right shunt, mild MR, moderate to severe tricuspid regurgitation, and dilated, hypertrophied left and right ventricles with good systolic function. Moderate (3.5 mm) VSD was observed at the subaortic outlet septum. The aortic valve was thickened and bicuspid with (6 mm annulus), and the peak pressure gradient (PG) across the aortic valve was 65 mmHg (a mean of 30 mmHg). A large PDA (3.6 mm) was observed at the pulmonary end with left to right nonrestrictive shunt. The pulmonary valve was thickened and dysplastic (8 mm annulus); a peak PG of 65 mmHg was noted. The patient was on furosemide, captopril, and spironolactone.   Postcardiac catheterization, she was extubated, hemodynamically stable and without heart failure, then transferred to the pediatrics ward. Two days later, she was transferred to the pediatric ICU and was reintubated due to lung collapse. Two weeks later, the patient's condition deteriorated. There was bleeding from the mouth and in the endotracheal tube suggesting acute lung injury. During this period of respiratory compromise, the cardiac parameters were normal. Despite aggressive management by adrenaline, cryoprecipitate, and factor 7 replacement, the patient developed severe bradycardia, desaturation, and hypotension. After 30 min of cardiopulmonary resuscitation, which failed to revive her, the patient was declared dead.
The age of presentation in the 48 cases varied, ranging from the prenatal period to 55 years. It was speculated that an early presentation indicated severe disease. Almost all the other published cases in the literature were associated with congenital cardiac lesions: ASD was present in nine cases [5-7, 10, 13-14], VSD was identified in eight cases [7,[9][10][11][15][16], and an atrioventricular canal defect was described in one case [12]. To the best of our knowledge, our case makes a unique combination to the medical literature on the topic in which the presence of combination of two left-to-right intracardiac shunts (ASD and VSD) and one left-to-right shunt at the great arteries level (i.e., PDA) were first described. This unique combination of biventricular outflow obstruction, associated with atrioventricular septal defects and PDA required special hemodynamic consideration. From an etiological point of view, such a combination provides a clue to understanding cardiac dysmorphogenesis processes in humans.
An evaluation was performed of the management of biventricular stenosis in the literature to identify the most optimal approach. Most cases published in the last century are characterized by poor outcomes, especially those prior to the era of catheter-based interventions. Specific management guidelines are not available in the medical literature due to the rarity of this condition. Clearly, evidence-based interventions rely on published case reports. Of the 48 cases, only nine of them were managed by balloon valvuloplasty. Ours was the 10th published case. In the current study, pulmonary valvuloplasty was not performed owing to the presence of a significant left-to-right shunt at three levels: ventricular, atrial, and great levels. The presence of native pulmonary valve stenosis is considered to be protective against pulmonary circulation overflow. Aortic valve PG dropped from 65 to 22 mmHg. This was accompanied by a significant improvement in the cardiac hemodynamic parameters and the patient's general condition. The planned next step was to perform total repair: septal defects closure, PDA ligation, and pulmonary valvotomy. The patient's condition deteriorated because of sepsis with Gram-negative bacilli (Escherichia coli) despite the remarkable stable cardiac parameters. The current scenario is a strong indicator, for future cases to perform a meticulous search for associated extracardiac and systematic involvement. In our case, the deterioration in the infant's condition is mainly attributed to sepsis, liver failure with increasing liver enzymes and deteriorated coagulation profile followed by pulmonary hemorrhage, and respiratory failure terminated by disseminated intravascular coagulation. Extracardiac involvement is significantly associated with CHD. This association is more pronounced with an increase in CHD complexity. Comparative studies carried out in our region on 2,020 cases, documented the involvement of other systems in one-third of CHD cases versus 10% in the controls. Anomalies of the central nervous system, hematological system, and gastrointestinal system were the most frequent associated extracardiac anomalies [17][18]. Meticulous search for associated extracardiac anomalies must be a critical part of the management plan in similar scenarios.

Conclusions
Biventricular outflow obstruction is rarely described. Of the 48 published cases, only nine of them were managed by balloon valvuloplasty. Ours was the 10th published case. To the best of our knowledge, this combination of biventricular outflow obstruction ASD, VSD, and PDA were first described. Future cases should be recognized early with meticulous search for extracardiac anomalies to avoid tragic hemodynamic outcomes.

Additional Information Disclosures
Human subjects: Consent was obtained by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.