Successful surgical intervention for Berry syndrome combined with severe pulmonary hypertension: a case description

Introduction

Berry syndrome is a rare congenital cardiovascular malformation characterized by a combination of an aortopulmonary septal defect (APSD), an anomalous origin of the right pulmonary artery from the aorta (AORPA), an interrupted aortic arch (IAA), a patent ductus arteriosus (PDA), and an intact ventricular septum (1). This condition occurs in approximately 0.046% of patients with congenital heart disease (2). Most affected children undergo early surgical intervention shortly after birth. In complex congenital heart disease, hemodynamic abnormalities associated with APSD can lead to the progressive elevation of pulmonary artery pressure, thereby significantly increasing perioperative risks and mortality.

This article presents a case of delayed diagnosis with significant clinical relevance: at the age of 4 years, the patient was diagnosed with complex cardiac malformations accompanied by severe pulmonary hypertension (PH) following multimodal imaging studies, including echocardiography, computed tomography angiography (CTA), and right heart catheterization (RHC) for hemodynamic evaluation. After a comprehensive clinical assessment, successful radical surgery was performed, resulting in a favorable prognosis. Despite some limitations in the completeness of clinical data, this case provides a systematic demonstration of an integrated assessment strategy for patients with advanced complex congenital heart disease, incorporating clinical symptomatology, imaging findings, and hemodynamic parameters. This article serves as a valuable reference for personalized therapeutic decision-making in cases of complex congenital heart disease combined with severe PH, particularly in relation to the optimal surgical timing and multimodal imaging evaluation.

Case presentation

A 4-year-old female patient was admitted to the hospital with complaints of chest tightness, shortness of breath, and excessive sweating following physical activity for over a year. The patient had no family history of hereditary diseases, did not experience dizziness or visual obscurations, and at birth, had exhibited feeding difficulties along with frequent crying episodes. Blood pressure measurements were obtained in all extremities, yielding readings of 92/50 mmHg in the left upper extremity, 99/59 mmHg in the right upper extremity, 100/52 mmHg in the left lower extremity, and 91/47 mmHg in the right lower extremity. Additionally, the oxygen saturation level was documented at 98.5%. A grade 4/6 systolic blowing murmur was auscultated over the third and fourth left intercostal spaces along the sternal border. Laboratory findings revealed a hemoglobin level of 148 g/L, a red blood cell count of 5.26×10¹²/L, and an N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration of 1,105.00 pg/mL.

The electrocardiogram revealed sinus tachycardia. Chest X-ray showed an enlarged cardiac silhouette and increased lung markings bilaterally. Transthoracic echocardiography revealed the following findings: an APSD with a maximum diameter of approximately 28 mm; a right pulmonary artery originating from the posterior wall of the ascending aorta, with an opening diameter of 21 mm and a distance of 15–20 mm from the aortic annulus; color Doppler flow imaging showed antegrade flow signals from the ascending aorta to the right pulmonary artery; an arterial conduit was identified between the left pulmonary artery and the descending aorta, with bidirectional reddish-blue flow signals; the aortic arch terminated as a blind end after giving off the left subclavian artery, with no detectable continuation of the descending aortic arch. Pulmonary artery systolic pressure was estimated at 96 mmHg, with mild-to-moderate tricuspid regurgitation and moderate mitral regurgitation (Figure 1A-1C). The CTA findings suggested an APSD (type II), with an AORPA and IAA (type A), and the presence of a PDA (measuring approximately 11 mm in diameter) (Figure 1D-1F). Based on these observations, Berry syndrome was highly suspected.

Figure 1 Echocardiography combined with CTA for diagnosing Berry syndrome. (A) The short-axis view of the large artery showed a septal defect of the main pulmonary artery. (B) Spectral analysis of ductus arteriosus flow. (C) Minimal to moderate tricuspid regurgitation, and moderate mitral regurgitation. (D) Preoperative CTA showed an APSD (type II); (E) a PDA (measuring approximately 11 mm in diameter); and (F) an IAA (type A). APSD, aortopulmonary septal defect; CTA, computed tomography angiography; IAA, interrupted aortic arch; PDA, patent ductus arteriosus.

Genetic monitoring of the child was recommended, but the family refused. To more accurately assess the severity of PH, RHC was performed under general anesthesia after adequate management of heart failure and optimization of fluid balance. The measured pulmonary artery pressures were as follows: systolic pulmonary artery pressure (sPAP): 73 mmHg; mean pulmonary artery pressure (mPAP): 37 mmHg; and diastolic pulmonary artery pressure (dPAP): 19 mmHg. Using the Fick principle for calculation, the pulmonary vascular resistance (PVR) was found to be 11.2 Wood units (WU), the PVR index (PVRi) was 5.9 WU·m², and the systemic vascular resistance (SVR) was 17.6 WU. Additionally, the left ventricular end-diastolic pressure was recorded at 18 mmHg.

Based on the comprehensive multimodal imaging assessment, RHC findings, clinical manifestations, and the child’s developmental status, we concluded that a one-stage radical surgical intervention was the optimal therapeutic strategy. The procedure included mitral annuloplasty, the ligation and division of the PDA, aortic arch reconstruction, and APSD repair using an autologous pericardial patch. Further, an internal tunnel was constructed with a patch to redirect blood flow from the main pulmonary artery to the right pulmonary artery through the main pulmonary septal defect.

Postoperatively, the patient was initiated on bosentan dispersible tablets (32 mg twice daily) as targeted therapy for PH to reduce PVR. Diuretic management included spironolactone (10 mg once daily) and hydrochlorothiazide (12.5 mg once daily) to optimize volume status and mitigate heart failure symptoms. Follow-up assessments were performed at 14 days, 3 months, and 9 months post-surgery. Final echocardiography revealed a sPAP of 39 mmHg (Figure 2A-2D). The child remained asymptomatic, demonstrating enhanced exercise tolerance and progressive weight gain.

Figure 2 Spectrum of tricuspid regurgitation. (A) Spectrum of tricuspid regurgitation prior to surgery (Vmax =4.90 m/s, PG =97 mmHg). (B) Fifteen days post-surgery (Vmax =3.77 m/s, PG =57 mmHg). (C) Three months post-surgery (Vmax =2.95 m/s, PG =35 mmHg). (D) Nine months post-surgery (Vmax =3.00 m/s, PG =36 mmHg). PG, pressure gradient.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s), and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was provided by the patient’s legal guardians for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

In patients with Berry syndrome, the presence of an APSD accompanied by an AORPA results in a substantial left-to-right shunt at the great vessel level. This hemodynamic disturbance precipitates early-onset progressive PH in neonates. Additionally, the pathological shunt reduces effective ascending aortic blood flow, thereby impairing aortic arch development and increasing the risk of arch hypoplasia (3). Notably, persistent patency of the arterial duct provides compensatory perfusion to the lower body circulation. This adaptive mechanism temporarily mitigates hemodynamic deterioration, prolonging survival in untreated patients. However, given the inevitable progression to irreversible pulmonary vasculopathy and aortic arch maldevelopment, definitive surgical correction during the neonatal period is imperative to achieve anatomical reconstruction and hemodynamic normalization. A systematic literature review of 89 Berry syndrome cases revealed 100% mortality among untreated patients, with most succumbing within the first postnatal month (4). Only rare cases demonstrated long-term survival without intervention. These findings underscore the critical importance of prompt surgical repair on diagnosis.

In this article, we described a rare case of Berry syndrome associated with severe PH that was successfully managed by a one-stage surgical intervention, resulting in a favorable prognosis. In this case, the child was referred for evaluation due to the detection of a heart murmur and decreased exercise tolerance. Echocardiography remains the primary imaging modality for diagnosing such conditions. However, during the sonographic examination, the identification of an APSD and AORPA should prompt suspicion of Berry syndrome and necessitate further assessment for concomitant aortic arch stenosis or interruption. A combined CTA is recommended to minimize the risk of misdiagnosis. When assessing the eligibility of patients with complex congenital heart disease complicated by severe PH for cardiac corrective surgery, there are notable limitations in relying solely on non-invasive imaging parameters obtained from echocardiography and CTA. While existing studies have reported a strong correlation between echocardiography estimates of pulmonary artery pressure and measurements obtained via RHC (5), its clinical utility in evaluating pulmonary artery pressure in the context of complex congenital heart disease remains constrained by anatomical variability and hemodynamic complexity (6).

Notably, RHC not only serves as the “gold standard” for diagnosing PH but also provides critical quantification of disease severity through the direct measurement of key hemodynamic parameters, including pulmonary artery pressure, PVR and the PVRi. According to the expert consensus statement (7,8), children with congenital heart disease PH who are in a critical state for surgical correction (in the gray zone), defined as a PVRi 6–8 WU·m² and PVR/SVR 0.3–0.5, should undergo acute vasodilator testing (AVT) for further assessment. However, currently there is a lack of clear positive reaction standards for AVT or specific hemodynamic indicators that can reliably predict the reversal of postoperative PH and a good prognosis in the long term. Moreover, for patients with complex congenital heart disease combined with PH, this predictive ability is particularly limited.

In this case, the child underwent a catheter examination under general anesthesia with tracheal intubation [fraction of inspiration oxygen (FiO₂) =100%], but did not undergo AVT. Based on the RHC data and guideline standards, the child appeared to be in a critical state for surgical correction; however, the lack of AVT represents a certain limitation. In this case, the final surgical decision was based on a comprehensive assessment of the following multiple dimensions: (I) key hemodynamic data: The Qp/Qs was 8.3, confirming significant left-to-right shunting, and the pulmonary circulation showed a markedly high-flow load; the PVRi was 5.9 WU·m², and thus did not exceed the absolute surgical contraindication threshold (>8 WU·m²); the dPAP was low, suggesting that the degree of pulmonary vascular remodeling might be relatively mild (9). (II) Anatomical and pathophysiological considerations: It was thought that the large PDA shunt might partially buffer pulmonary artery pressure and delay the progression of pulmonary vascular lesions. The child had no family history of PH or other additional high-risk factors. The family had a positive attitude toward the radical treatment and was willing to bear the surgical risk.

Considering various factors, after a comprehensive assessment of the benefits and risks of the surgery, a one-stage surgical cure was performed for this child. Surgical intervention is the only way to improve the long-term prognosis of this disease, and the treatment effect is closely related to age, malformation category, and complexity. If postoperative PH persists, targeted pulmonary vascular dilators such as phosphodiesterase-5 inhibitors and endothelin receptor antagonists can be considered, based on PH crisis stratification, for single-drug, dual-drug, or triple-drug therapy (8). In this case, the child was treated with bosentan dispersible tablets (32 mg twice a day) and diuretics, and after 9 months of follow-up, echocardiography monitoring showed a significant reduction in pulmonary artery pressure, the child’s exercise tolerance significantly increased, and the child had a good prognosis. A previous study has shown that in 13 patients with Berry syndrome, among those aged over 3 years, severe PH is usually difficult to reverse after surgery, thus the short- and long-term postoperative prognosis of such patients is poor (10). In this case, we combined clinical information, multimodal imaging techniques, right heart catheter examination, and the application of targeted pulmonary vascular drugs after surgery to increase the possibility of surgical opportunities for this child with complex congenital heart disease.

This rare case was successfully treated with radical surgery. The details of the treatment process have been detailed in this article to provide a reference and an overview of our experience for clinical medical workers.

Acknowledgments

None.

Footnote

Funding: This work was supported by the Natural Science Foundation of Gansu Province (No. 24JRRA1048 to Z.G.) and the Gansu Provincial Hospital Intramural Fund Clinical Research Category (No. 23GSSYD-19).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-937/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s), and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was provided by the patient’s legal guardians for publication of this article and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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