We report the case of a boy diagnosed at age 9 with a large aortopulmonary septal defect and Eisenmenger syndrome, highlighting the challenges of late diagnosis and management of fixed pulmonary hypertension. Over the course of six years (2018–2024), the patient underwent several follow-ups, including invasive hemodynamic assessments and echocardiography, revealing progressive pulmonary vascular disease. Despite the administration of medical therapy with sildenafil, bosentan, and antiplatelets, the patient’s condition remained unfavorable due to fixed pulmonary vascular obstructive disease. This case underscores the importance of early diagnosis and the complexities of managing advanced pulmonary hypertension in congenital heart defects.

childhood, pulmonary hypertension, congenital heart defect

Aortopulmonary septal defect (APSD) is a rare congenital heart anomaly that can result in progressive pulmonary hypertension if not corrected early.^[1] Eisenmenger syndrome represents a significant complication of unrepaired APSD, with fixed pulmonary vascular resistance and a reversal of shunting leading to cyanosis and systemic hypoxemia.^[2] Late diagnosis and limited therapeutic options make the management of such patients challenging. In this case, the absence of an audible heart murmur during infancy and early childhood contributed to the delayed identification of the defect. The child was considered healthy based on routine pediatric check-ups, highlighting the limitations of standard clinical examinations in detecting congenital heart defects. Here, we present a six-year follow-up of a patient with late-diagnosed APSD and Eisenmenger syndrome, illustrating the natural progression of the disease and the response to medical therapy. This case emphasizes the urgent need to implement neonatal screening programs for congenital heart defects to prevent delayed diagnoses and irreversible complications.

We present a case of a late-diagnosed rare congenital heart defect that led to irreversible changes in the pulmonary vasculature, precluding surgical correction. The therapeutic approach focuses on reducing pulmonary vascular resistance and improving physical capacity and quality of life through pulmonary vasodilators. APSD, also referred to as aortopulmonary window, is a rare congenital defect with direct communication between the ascending aorta and the pulmonary artery. This communication results in a left-to-right shunt, which increases pulmonary blood flow and leads to volume overload and pulmonary hypertension.^[1] In many cases, the presence of a continuous heart murmur during infancy may prompt early diagnosis; however, in our patient, no murmurs were detected during multiple routine examinations. This atypical presentation delayed referral to a cardiologist and underscores the need for improved detection strategies. APSD was first described pathologically by J. Elliotson in 1830.^[4] His early observations laid the groundwork for understanding this rare anomaly. Aortopulmonary window is an extremely rare defect, accounting for approximately 0.2% to 0.6% of all congenital heart malformations. There is a noted male predominance, which aligns with our case. It is often associated with other cardiac anomalies, including coarctation of the aorta or interrupted aortic arch.^[5] Genetic syndromes like VACTERL and Bohring-Opitz have been associated with APSD.^[6,7] The equalization of pressures between the aorta and pulmonary artery, combined with persistent pulmonary hypertension after birth, likely accounts for the absence of an audible murmur, which in turn contributed to the delayed diagnosis, as observed in our case.

Aortopulmonary septal defects are classified into three types based on their location and extent, as described by Mori et al. Type I (proximal) occurs between the posterior wall of the ascending aorta and the lateral wall of the main pulmonary artery. Type II (distal) is located between the posterior wall of the ascending aorta and the anterior wall of the origin of the right pulmonary artery. Type III, the rarest form, represents a combination of both type I and type II defects, as seen in our case.^[8]

The diagnosis of Eisenmenger syndrome (ES) requires a comprehensive approach that integrates clinical findings, imaging studies, and hemodynamic assessments.^[9] Definitive diagnosis, particularly for PH with elevated pulmonary vascular resistance (PVR), requires cardiac catheterization, which remains the gold standard. This invasive procedure allows precise measurement of mean pulmonary arterial pressure (mPAP), PVR, and other hemodynamic parameters.^[10] Initially diagnosed through cardiac catheterization, current methods now prioritize noninvasive echocardiographic assessment.^[9] Echocardiography is the cornerstone of diagnosing APSD and was instrumental in identifying right atrial and ventricular dilation, pulmonary hypertension, and the aortopulmonary communication in this patient. Advanced imaging techniques such as CT angiography provided additional clarity by delineating the size and location of the defect and confirming the associated pulmonary vascular changes.^[11]

Without surgical correction in the first months of age, chronic pulmonary hypertension can progress to Eisenmenger syndrome, characterized by right-to-left shunting and irreversible pulmonary vascular disease, as observed in this case.^[2] Eisenmenger syndrome represents a significant shift in the management of APSD, as surgical correction becomes contraindicated due to the risk of exacerbating right-to-left shunting and worsening hypoxemia.^[12]

The management of Eisenmenger syndrome is multifaceted and guided by the severity of symptoms, hemodynamic profile, and the presence of complications. As described in the literature, therapeutic strategies aim to improve quality of life, alleviate symptoms, and address secondary complications, rather than reverse the underlying vascular remodeling.^[9] Pharmacological therapy is central to care, with sildenafil, a phosphodiesterase-5 inhibitor (PDE-5i), and bosentan, an endothelin receptor antagonist (ERA), forming the basis of this patient’s treatment regimen.^[9,13,14] Recent advancements, such as prostacyclin analogs and soluble guanylate cyclase stimulators (e.g., riociguat), have effectively reduced pulmonary vascular resistance and improved outcomes in high-risk patients. However, their use in Eisenmenger syndrome remains limited due to the lack of robust clinical trials specific to this subgroup. Not all classes of pulmonary hypertension (PH) medications are approved for use in pediatric populations. For instance, oral prostacyclin receptor agonists, such as selexipag, belong to the same therapeutic spectrum as prostacyclin analogs but differ in their structure, pharmacokinetics, and route of administration. While selexipag offers the convenience of oral administration, its safety and efficacy in children are still under investigation, and further clinical trials are necessary before it can be routinely applied in pediatric PH management.‌^[3] Supportive measures included careful avoidance of long-term oxygen therapy, given the risk of exacerbating right-to-left shunting. Antiplatelet therapy was also introduced to mitigate the risk of thromboembolism, which is heightened in the setting of secondary erythrocytosis and sluggish pulmonary flow. Regular monitoring of symptoms, oxygen saturation, and biomarkers such as BNP was crucial for assessing disease progression and guiding adjustments in therapy. BNP may not always correlate with the severity of Eisenmenger syndrome in some patients, highlighting the importance of combining biomarker data with hemodynamic and clinical parameters for accurate risk assessment. In cases of advanced disease and progressive deterioration, as seen in this patient, lung transplantation becomes an important consideration. According to current guidelines, early referral for transplantation evaluation is recommended for patients with severe functional limitations, refractory symptoms, or elevated PVR.^[9,10]

The prognosis for untreated APSD is poor, emphasizing the critical need for early detection and intervention.^[11]

This six-year follow-up of a boy with APSD and Eisenmenger syndrome highlights the complexities of managing advanced pulmonary hypertension in congenital heart defects. Early diagnosis and timely intervention are critical to prevent progression to Eisenmenger physiology. Our case demonstrates that the absence of a heart murmur does not exclude the presence of significant congenital heart disease and reinforces the necessity of neonatal screening programs. For inoperable patients, current management strategies emphasize long-term medical therapy and symptom control; however, significant challenges remain. Future research should prioritize developing targeted therapies for irreversible pulmonary vascular disease and refining risk stratification models to guide earlier and more personalized interventions.

The authors have declared that no competing interests exist.

The authors declared that no clinical trials were used in the present study.

The authors declared that no experiments on humans or human tissues were performed for the present study.

The authors declared that no informed consent was obtained from the humans, donors or donors’ representatives participating in the study.

The authors declared that no experiments on animals were performed for the present study.

The authors declared that no commercially available immortalised human and animal cell lines were used in the present study.

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No funding was reported.

All authors contributed to the study conception and design. Material preparation and data collection were performed by Daniela Milanova-Ilieva, Kostadin Ketev, and Anna Kaneva. Data analysis was conducted by Anna Kaneva and Daniela Milanova-Ilieva. Daniela Milanova-Ilieva wrote the first draft of the manuscript, with Anna Kaneva providing valuable input and revisions. All authors provided comments on previous versions of the manuscript. All authors read and approved the final manuscript.

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