Case report

A 4-year-old girl was referred to the Paediatric Cardiology Department of our hospital, diagnosed with pulmonary hypertension. She had a history of repeated spastic bronchitis from the age of 1 year, which led to hospitalisations at the ages of 2 and 4 years. She had no other symptoms and had experienced normal growth and development.

Her physical examination was unremarkable except for a split-second heart sound, with slightly increased P2 sound. Oxygen saturation was higher than 95% in room air; electrocardiogram presented sinus rhythm and 90° QRS axis. Echocardiography showed mild flow acceleration in both superior pulmonary veins, type I interventricular septum with paradoxical movement, and mild tricuspid insufficiency, with an estimated systolic right ventricular pressure of 48 mmHg – 45% of systemic blood pressure. Sleep breathing disorders, thyroid or immune anomalies, hepatic or portal abnormalities, and human immunodeficiency virus infection were ruled out. Frontal chest radiograph revealed a shadow along the right heart border (Fig 1), identified in a CT pulmonary angiogram as an anomalous venous structure connecting the superior and inferior right pulmonary veins, describing a tortuous route through the lung (Fig 1). The dilated inferior pulmonary vein drained into the left atrium. The left pulmonary veins were normal, except for a mild stenosis of the upper left pulmonary vein. Cardiac catheterisation found mildly elevated pulmonary pressure, mild left upper pulmonary vein stenosis – 2 mmHg mean gradient – and normal bilateral pulmonary wedge pressure (Supplementary table 1). Flow was quantified by MRI, with 35% flow to the left lung and 65% to the right lung. Right pulmonary artery hypoplasia and aberrant arterial systemic lung supply were ruled out.

Figure 1

Left: chest X-ray showing the shadow of the meandering right pulmonary vein. Centre and right: CT scan images of the meandering right pulmonary vein.

Treatment of her bronchitis was intensified, adding maintenance inhaled budesonide, with significant decrease in bronchoconstriction episodes. During the next 3 years, in spite of dramatic improvement of her respiratory symptoms, her pulmonary hypertension progressed rapidly, with effort dyspnoea unrelated to bronchoconstrictive episodes – NYHA functional class IIIa. Echocardiography showed increased pulmonary pressure, hypertrophy, dilation, and dysfunction of the right ventricle. Repeated cardiac catheterisation revealed severe pulmonary hypertension unresponsive to nitric oxide, normal pulmonary wedge pressure (Supplementary table 1), pruning, and loss of peripheral vessels on angiography, showing progression compared with the angiographies obtained previously (Fig 2). Treatment with sildenafil was initiated, and was increased up to 40 mg t.i.d., with poor improvement in her functional class. Ambrisentan 7.5 mg o.d. was included 6 months later, with significant improvement in her functional class (NYHA I), which had remained stable after 4 years of combined therapy.

Figure 2

Pulmonary wedge angiographies at 4 (up) and 7 (down) years of age, showing worsening of the tapering and pruning of the distal vessels, with remarkable loss of distal vascular bed at the age of 7 years.

Discussion

Congenital pulmonary venolobar syndrome refers to a wide spectrum of pulmonary developmental anomalies that involve abnormal connections of the pulmonary parenchyma, the pulmonary and systemic vasculature, and, rarely, the gastrointestinal tract. Anomalies involved in this syndrome may appear in isolation or in combination, and thus the clinical presentation of this syndrome is variable, depending mainly on the presence of associated cardiac abnormalities.Reference Woodring, Howard and Knaga ^{1 –} Reference Goodman, Jamshidi and Hipona ⁵ “Scimitar syndrome”, described in 1960, consists of variable combinations of hypoplasia of the right lung and right pulmonary artery, dextroposition of the heart, anomalous arterial supply to the right lower lobe, and anomalous pulmonary venous drainage of the right lung into the inferior caval veinReference Sanger, Taylor and Robicesek ⁴ causing the characteristic “scimitar sign” – a Turkish sword-shaped shadow along the right heart border on chest X-ray. Infant forms, presenting with respiratory insufficiency, heart failure, or pulmonary hypertension, are usually associated with systemic arterial supply (sequestrum), severe right lung hypoplasia, and abnormal drainage of the right pulmonary vein into the inferior caval vein. In the “adult form”, patients can remain asymptomatic and have an incidental diagnosis through a chest X-ray.

On the contrary, meandering right pulmonary vein – pseudo-scimitar syndrome, scimitar variant – Reference Rodrigues, Ritchie and Murchison ^{3 ,} Reference Goodman, Jamshidi and Hipona ⁵ which can also associate the classical right parasternal shadow in the chest X-ray, is rarely associated with severe lung or heart malformations.

Our patient presented progressive pulmonary hypertension, with normal pulmonary wedge pressure and without sustained hypoxia or hypercarbia, behaving like idiopathic pulmonary hypertension, which responded to combined therapy with phosphodiesterase-5 inhibitors and endothelin receptor antagonist. Several publicationsReference Salerno, Guccione, Malena and Cutrera ^{8 ,} Reference Dusenbery, Geva and Seale ⁹ have reported pulmonary hypertension associated with scimitar syndrome and horseshoe lung associated with significant heart anomalies; however, to the best of our knowledge, there are no reports of isolated meandering pulmonary vein associated with severe pulmonary hypertension. Mechanisms linking congenital abnormalities of the pulmonary veins and the development of pulmonary hypertension are not completely understood.Reference Endo, Yamaki, Hata, Saiki and Tabayashi ¹⁰ We hypothesise that the prenatally conditioned morphological abnormalities in the pulmonary veins and lung development could be associated with histological abnormalities of the arterioles, capillaries, lymphatics, and venules and/or to disrupted molecular pathways causing progressive vascular re-modelling, although this cannot be proved without lung tissue evaluation.

Congenital anomalies of the pulmonary vessels can go unnoticed without the use of an imaging technique (MRI or CT scan), which should be included in the initial evaluation of every pulmonary hypertension case. In light of cases like ours, clinical and echocardiographical follow-up of these patients is mandatory, even if the initial evaluation does not suggest the severity of the pulmonary hypertension. Some patients with pulmonary hypertension associated with congenital anomalies of the pulmonary veinsReference Cerro, Abman and Diaz ⁶ can benefit from treatment with phosphodiesterase-5 inhibitors and endothelin receptor antagonists.