If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
Primary pulmonary vein stenosis (PVS) is rare within the pediatric population and its pathophysiology remains unclear, especially as to how the histopathology relates to its refractoriness to treatment. We report the case of a 4-month-old girl with primary PVS. The lesion in this patient was characterized by fatal obstruction of intraparenchymal small pulmonary veins, associated with localized stenosis at the four pulmonary veno-atrial junctions. All four localized stenoses underwent transcatheter stent implantation. Although the procedure was technically successful, her clinical status failed to improve, and she died 2 months after stenting. Histopathological examination of lung specimens showed severe luminal obstruction by marked intimal proliferation with fibrosis in the intraparenchymal small pulmonary veins, and these findings were present in every lobe. To the best of our knowledge, the histopathological findings and clinical course in this case, including the response to treatments, are extremely rare. We suggest that the histological findings of the small pulmonary veins are important in deciding the indication and appropriate timing of intervention.
<Learning objective: The outcome of primary pulmonary vein stenosis has remained poor despite aggressive treatment, while the indication and appropriate timing of intervention has not been clarified. The histological findings of small pulmonary veins are important to predict the response to treatment and outcome, and early intervention might prevent the secondary progression of this disease.>
Pulmonary vein stenosis (PVS) is usually associated with other congenital heart diseases, such as total anomalous pulmonary venous connection and heterotaxy syndrome, and primary PVS, i.e. isolated cardiac lesion with normal pulmonary vein connection, is rare within the pediatric population [
]. The Pediatric Cardiac Care Consortium (PCCC; Minneapolis, MN, USA) database reported an incidence of primary PVS of 0.03% (31 of 98,126) in a population of patients with congenital heart disease who underwent catheterization or surgery [
], while the indication and appropriate timing of intervention has not been clarified.
A 3-month-old girl, born at full term and body weight of 2852 g following an uncomplicated pregnancy was noted to be failing to thrive. She had no specific family history. She was admitted to our department at the age of 4 months because of cyanosis and respiratory distress.
On admission her body weight was 5.1 kg. She had dyspnea with retractions and deep cyanosis. Her SpO2 was 74%, heart rate 160 beats/min, systolic blood pressure 90 mmHg, and respiratory rate 50 min–1. The second heart sound was accentuated, while a grade 2/6 pansystolic murmur was audible over the lower left sternal border. Her jugular vein was distended and the liver was palpable 4 cm below the right costal margin.
Laboratory data were non-specific for complete blood count, electrolytes, renal, and hepatic profiles. A chest X-ray showed a cardiothoracic ratio of 57% with marked pulmonary venous congestion and pulmonary emphysema (Fig. 1a) . Her electrocardiogram documented right ventricular hypertrophy, right atrial enlargement, and sinus rhythm. Echocardiogram showed severe pulmonary hypertension with a dilated right ventricle, moderate tricuspid valve regurgitation and right-to-left shunting across the foramen ovale. Pulmonary veins were not considered to be obstructed on echocardiography, because specific findings like non-phasic flow or flow velocity acceleration were not recognized (Fig. 2). Inhaled nitric oxide and intravenous epoprostenol were started immediately after admission. The pulmonary arterial pressure and oxygen saturation improved shortly after starting treatment; however, this improvement was followed by a dramatic deterioration of pulmonary venous congestion (Fig. 1b). Subsequently, her clinical condition remained critical associated with severe pulmonary hypertension, right heart failure, and pulmonary venous congestion. Her condition gradually deteriorated despite various medical treatments. When she was 11 months, we performed computed tomography and cardiac catheterization to evaluate the morphology of the pulmonary veins and assess if there was any indication for intervention.
Cardiac catheterization demonstrated a pulmonary arterial pressure of 100/60 (mean 75) mmHg; pulmonary to systemic pressure ratio was 0.76. Pulmonary venous pressure was also increased to 40 mmHg, while pulmonary capillary wedge pressure was 23 mmHg. The pulmonary venous pressure data were obtained by direct insertion of catheter into pulmonary vein, so the high pressure might be influenced by obstruction of the inserted catheter. Left ventricular end-diastolic pressure was 20 mmHg and central venous pressure was 17 mmHg. We consider that elevated left ventricular end-diastolic pressure probably resulted from severe compression by highly dilated right ventricle. Computed tomography and pulmonary venous angiography documented localized stenosis of all 4 pulmonary veins at the veno-atrial junction (Fig. 3, Fig. 4) , and we decided to perform transcatheter stent implantation for these stenoses.
We sequentially implanted Express vascular SD stent (Boston Scientific, Natick, MA, USA) in 4 pulmonary veins with technical success (Fig. 4b). As some of these lesions were markedly firm, an ultra-high-pressure balloon such as Conquest (Bard, Tempe, AZ, USA) was required for final dilatation in the right pulmonary veins. The final diameter of the balloon was 7 mm in the right upper and lower pulmonary veins, 6 mm in the left lower, and 5 mm at left upper pulmonary vein. Although the lumen of the pulmonary vein at the stenotic veno-atrial junction was secured sufficiently, her hemodynamic condition remained critical; the pulmonary to systemic pressure ratio only decreased from 0.76 to 0.70, and she died 2 months after the stent implantation.
Autopsy was performed, and lung specimens were obtained from bilateral lungs. Histopathological examination showed severe luminal obstruction by marked intimal proliferation with fibrosis in the intraparenchymal small pulmonary veins, and these findings were present in every lobe (Fig. 5). There was no luminal obstruction without irreversible intimal fibrosis, in small pulmonary arteries, while internal elastic membrane was well extended which suggested effectiveness of the pulmonary vasodilator.
We report the case of an infant complicated by primary PVS, which is an extremely rare disease characterized by fatal obstruction of intraparenchymal small pulmonary veins, associated with localized stenosis of all 4 pulmonary veno-atrial junctions. Consequently, she developed severe pulmonary hypertension, right heart failure, and pulmonary venous congestion. Stenoses at the veno-atrial junction were effectively dilated by stent implantation, and small pulmonary artery lumen was well patent which suggested effectiveness of the pulmonary vasodilator. However, she failed to recover from the critical pulmonary hypertension. Therefore, we believe that the coexistence of fatal obstruction of small pulmonary veins is the main cause that contributed to ineffectiveness of various treatments in this patient. Previous reports have described that intimal proliferation in small pulmonary veins was shown in association with primary PVS [
]. Meanwhile, other authors hypothesized that PVS began as a discrete localized stenosis, which then progressed to involve longer segments of the intraparenchymal pulmonary veins, on the base of serial imaging studies [
]. The authors of a second report also speculated that as a discrete stenosis at the pulmonary veno-atrial junction would have progressed to diffuse obstruction of small pulmonary veins and finally to complete occlusion, early intervention should be important [
]. These reports suggested that obstruction in the small pulmonary vein in primary PVS might be a secondary change to increased venous pressure, caused by localized stenosis downstream. Consequently, we suppose that early stent implantation, before development of secondary small vein obstruction might have prevented the progression of the disease in this patient.
A patient diagnosed at 18 months of age, having initial mean pulmonary arterial pressures >33 mmHg or with bilateral vessel involvement was at significant high risk of lung death or transplantation, with the risk up to around 80% [
]. We believe that our patient inherently had extremely poor prognostic features despite any intervention. There may be more patients than previously understood who have the histological features of fatal obstruction of small pulmonary veins, similar to our patient, particularly in patients who do not respond to treatment. Therefore, histological findings of small pulmonary veins will be extremely important to decide the indication and appropriate timing of intervention. Although the cause of small pulmonary vein obstruction is probably multifactorial, it might be a secondary progression caused by localized stenosis in some cases. When small PVS already exists, response to intervention is more likely to be poor, so early intervention may be necessary as soon as possible to prevent secondary progression of small pulmonary vein obstruction, if primary PVS was recognized.
We reported an infant with primary PVS, characterized by fatal obstruction of intraparenchymal small pulmonary vein, associated with localized stenosis of all 4 pulmonary veno-atrial junctions. Stent implantation for these stenoses was not effective in this patient, mainly because of the small pulmonary veins obstruction. The histological findings of small pulmonary veins are extremely important to predict the response to treatment and outcome, and early intervention might prevent the secondary progression of this disease.
We thank Dr. Peter M. Olley, Professor Emeritus of Pediatrics, University of Alberta, and Dr. Setsuko Olley for language consultation.
Van Praagh S.
Anomalies of the pulmonary veins.
in: Allen H.D. Driscoll D.J. Shaddy R.E. Feltes T.F. Moss & Adams’ heart disease in infants, children, and adolescents. Lippincott Williams and Wilkins,