Authors: Li Chen, Cheng Wang, Jiachen Li, Lizhi Lv, Yongtao Wu, Gang Li, Guofeng Xing, Xiaoyong Jing, Zhimin Liu, Qiang Wang
Categories: Research, Idiopathic pulmonary arterial hypertension, Left lower pulmonary vein compression, Surgical treatment, Children
Source: Journal of Cardiothoracic Surgery
Authors: Li Chen, Cheng Wang, Jiachen Li, Lizhi Lv, Yongtao Wu, Gang Li, Guofeng Xing, Xiaoyong Jing, Zhimin Liu, Qiang Wang
To investigate, through four clinical cases, whether compression-induced deformation of the left lower pulmonary vein by the descending aorta is an etiological factor in certain cases of severe pulmonary arterial hypertension (PAH) in children.
Four pediatric patients with severe PAH and left lower pulmonary vein stenosis (PVS) due to external compression by the descending aorta underwent surgical repair under general anesthesia with hypothermic extracorporeal circulation. The first patient underwent patch augmentation of the left lower pulmonary vein using pericardium. The remaining three patients underwent left lower pulmonary vein reimplantation to relieve the compression.
Preoperatively, following oxygen inhalation, the total pulmonary resistance indexed to body surface area in the first three patients was 11.7, 12.6, and 20.2 Wood units × m², respectively. Intraoperative observation confirmed normally developed left lower pulmonary veins with smooth intima and no intrinsic stenosis. Postoperatively, pulmonary artery pressure normalized in all cases. Computed tomography confirmed complete relief of the venous compression. Postoperative right heart catheterization in the first three patients showed indexed total pulmonary resistances of 8.6, 9.1, and 13.9 Wood units × m². All four patients exhibited significant symptomatic improvement.
In children with severe PAH of unexplained origin, impaired drainage of the left lower pulmonary vein secondary to compression by the descending aorta may be an initiating pathogenic factor. Surgical correction of this compression represents a novel therapeutic strategy for a subset of patients with idiopathic PAH.
Pulmonary arterial hypertension (PAH) is characterized by progressive obliteration of small pulmonary arteries, leading to increased pulmonary vascular resistance (PVR), right-heart failure, and death in approximately 25% to 60% of patients 5 years after diagnosis [1, 2]. Pediatric pulmonary arterial hypertension (PAH) exhibits feature of adult disease, but it is associated with several additional disorders and challenges that require unique approaches [3]. The common causes of pulmonary hypertension in children differ from those in adults. Idiopathic, heritable, drug-induced, and connective tissue disease-associated PAH are the primary etiologies of pulmonary hypertension (PH) in adults. However, in children, PH frequently occurs with congenital heart disease and genetic syndromes. In newborns and young infants, persistent PH is the most common phenomenon. Pulmonary vein stenosis (PVS), which has an inferior prognosis, can complicate the course of the disease and is emerging as an important cause of sustained PH, especially in ex-premature infants with bronchopulmonary dysplasia (BPD) [4–7]. PVS can arise from several etiologies, including congenital, acquired, and iatrogenic sources [8]. In children with PVS, the most common etiology is congenital, including abnormal pulmonary vein development and pulmonary vein compression. In this article, we analyzed three children with pulmonary arterial hypertension caused by pulmonary vein compression.
Four patients with suspected idiopathic pulmonary arterial hypertension (PAH) who were hospitalized at the Pediatric Heart Center of Beijing Anzhen Hospital and Fuwai Yunnan Hospital between February 9, 2022, and May 23, 2022, were included in this study. The inclusion criteria were as (1) mean pulmonary artery pressure (mPAP) > 20 mmHg at rest as measured by cardiac catheterization; (2) end-expiratory pulmonary artery wedge pressure (PAWP) (synonymous with pulmonary capillary wedge pressure [PCWP], but not with pulmonary capillary pressure) > 15 mmHg as measured by cardiac catheterization; (3) pulmonary vascular resistance (PVR) index > 3 Wood units (WU) ⋅ m2 as measured by cardiac catheterization; (4) no underlying disease known to be associated with PAH; and (5) cardiac computed tomography angiography (CTA) suggesting left lower pulmonary vein compression causing stenosis. The institutional review boards for clinical research at Beijing Anzhen Hospital and Fuwai Yunnan Hospital approved using patient medical records for this retrospective review. All the patients’ guardians provided informed consent.
All four patients underwent surgery under standard tracheal intubation with combined inhalational and intravenous anesthesia. The procedures were performed using moderate hypothermic extracorporeal circulation with ascending aortic occlusion. The left lower pulmonary vein was fully mobilized. In each case, no stenosis was identified in the trunk of the left lower pulmonary vein or at its left atrial orifice, and the lumen readily accommodated a 6‑mm probe. In the first patient, the left lower pulmonary vein was incised longitudinally from its proximal end to the left atrial orifice, extending toward the pulmonary hilum. The vein was then widened using an autologous pericardial patch from its orifice to the hilum. In the remaining three patients, the left lower pulmonary vein was transected and reimplanted into the left atrium with a continuous 6‑0 suture, taking care to avoid tension or torsion of the vessel.
In the first patient, pulmonary artery pressure (PAP) and right ventricular pressure (RVP) were measured after median sternotomy and compared with systemic arterial pressure. For the other three patients, RVP was continuously monitored intraoperatively via an indwelling catheter. PAP was recorded at three time after sternotomy, after weaning from extracorporeal circulation, and before chest closure.
Right-heart catheterization (RHC) was performed under intravenous anesthesia. Venous access was obtained via the femoral vein, and a 5‑French sheath was secured in place. A multipurpose catheter was advanced sequentially into the superior vena cava, inferior vena cava, right atrium, right ventricle, and pulmonary artery (PA). The following parameters were systolic, diastolic, and mean pulmonary artery pressure (PAP, mmHg); systolic, diastolic, and mean systemic arterial pressure (mmHg); right ventricular end‑diastolic pressure (RVEDP, mmHg); mean pulmonary capillary wedge pressure (PCWP, mmHg); pulmonary vascular resistance index (PVRI); systemic vascular resistance index; the ratio of pulmonary to systemic vascular resistance (Rp: Rs); mixed venous oxygen saturation (%); and systemic arterial oxygen saturation (%). Pulmonary hypertension (PH) was classified as mild (mean PAP 26–35 mmHg), moderate (mean PAP 36–45 mmHg), or severe (mean PAP > 45 mmHg).
The pigtail duct was taken into the left or right pulmonary artery (PA) across five French sheaths. Pulmonary angiography was not stopped until pulmonary vein imaging was performed.
The first patient was a 1-year-old boy weighing 5.7 kg. Echocardiography revealed a secundum atrial septal defect (ASD) measuring approximately 7 mm, with a bidirectional shunt and pulmonary hypertension. Based on trace tricuspid regurgitation, the estimated systolic pulmonary artery pressure was approximately 72 mmHg, with a mean pressure exceeding 66 mmHg. No pulmonary vein stenosis or increased flow velocity was detected. Right-heart catheterization yielded the following data after oxygen oxygen saturation in the superior vena cava was 79.3% (partial pressure 54.1 mmHg); pulmonary artery saturation was 85.1% (partial pressure 59.3 mmHg); left lower pulmonary vein saturation was 100.8% (partial pressure 99 mmHg); and femoral artery saturation was 89.5% (partial pressure 67.6 mmHg). The lower oxygen saturation in the pulmonary artery compared to the superior vena cava, along with the significantly lower saturation in the femoral artery relative to the pulmonary vein, indicated a bidirectional shunt through the ASD, predominantly right-to-left. After oxygen inhalation, the total pulmonary resistance was 11.7 Wood units × m². Selective angiography of the left lower pulmonary artery showed smooth pulmonary venous return; the diameter was 4 mm both proximal and distal to the narrowest point of the left lower pulmonary vein, with no apparent stenosis (Fig. 1). CT demonstrated stenosis at the orifice of the left lower pulmonary vein (Fig. 1).
Fig. 1The first patient had left pulmonary artery angiography and left lower pulmonary vein CTA images before and after surgery. Figure 1A shows preoperative left pulmonary artery angiography, revealing a left pulmonary artery diameter of 0.38 cm; Fig. 1B shows the postoperative left pulmonary artery angiography, which shows a left pulmonary artery diameter of 0.55 cm; Fig. 1C shows the preoperative CTA of the left lower pulmonary vein, which shows that the opening of the left lower pulmonary vein is compressed and narrowed, with an inner diameter of 0.17 cm, and the distal diameter is dilated, with an inner diameter of 0.50 cm; Fig. 1D shows the postoperative CTA of the left lower pulmonary vein, which shows relief of compression at the opening of the left lower pulmonary vein with an inner diameter of 0.32 cm and a distal inner diameter of 0.64 cm
The second patient was a 1-year-old girl weighing 10 kg. Echocardiography showed significant enlargement of the right atrium and ventricle, with D-shaped left ventricular compression due to right ventricular overload, and a patent foramen ovale. The predominant shunt was bidirectional with a right-to-left component, indicating severe pulmonary arterial hypertension. Based on mild to moderate tricuspid regurgitation, the estimated systolic pulmonary artery pressure was approximately 55 mmHg, with a mean pressure exceeding 31 mmHg. No pulmonary vein stenosis or increased flow velocity was detected. Right-heart catheterization data showed that after oxygen inhalation, the total pulmonary resistance was 12.6 Wood units × m². CT revealed stenosis of the left lower pulmonary vein (Fig. 2).
Fig. 2Preoperative left lower pulmonary vein CTA was performed on the second and third patients. Figure 2A shows the preoperative CTA of the left lower pulmonary vein in the second patient, which shows that the opening of the left lower pulmonary vein is compressed and narrowed, with an inner diameter of 0.20 cm and a distal inner diameter of 0.38 cm; Fig. 2B shows the preoperative pulmonary vein CTA of the third patient, which shows that the opening of the left lower pulmonary vein is compressed and narrowed, with an inner diameter of 0.11 cm
The third patient was a 9-month-old boy weighing 6.6 kg. Echocardiography demonstrated significant enlargement of the right atrium and ventricle, with septal displacement resulting in D-shaped left ventricular compression, pulmonary hypertension, and an estimated mean pulmonary artery pressure > 36 mmHg based on trace tricuspid regurgitation. No pulmonary vein stenosis or increased flow velocity was detected. Right-heart catheterization data after oxygen inhalation were as superior vena cava oxygen saturation 78.4% (partial pressure 54.7 mmHg); pulmonary artery saturation 73.7% (partial pressure 46.6 mmHg); pulmonary vein saturation 98% (partial pressure 97 mmHg); and femoral artery saturation 88% (partial pressure 65.4 mmHg). After oxygen inhalation, the mean pulmonary artery pressure was 42 mmHg, and the total pulmonary resistance was 20.0 Wood units × m². Right lower pulmonary artery angiography showed 60% stenosis at the entrance of the right lower pulmonary vein, with diameters of approximately 2 mm both proximal and distal to the stenosis. The orifice of the left lower pulmonary vein was narrow, with an internal diameter of 2 mm. CT imaging (Fig. 2) demonstrated narrowing at the entrance of the right lower pulmonary vein, compression and narrowing at the orifice of the left lower pulmonary vein, severe stenosis of the left main bronchus, and multiple exudative changes in both lungs.
The fourth patient was a 4-month-old girl weighing 5.9 kg. Echocardiography showed significant enlargement of all cardiac chambers, pulmonary hypertension, and an estimated mean pulmonary artery pressure > 65 mmHg based on trace tricuspid regurgitation. No pulmonary vein stenosis or increased flow velocity was detected. Due to the patient’s young age, right-heart catheterization was not performed. CT imaging (Fig. 3) revealed narrowing at the entrance of the right lower pulmonary vein, a well-preserved left lower pulmonary vein, severe stenosis of the left main bronchus, and multiple exudative changes in both lungs.
Fig. 3The fourth patient underwent left lower pulmonary vein CTA before and after surgery. Figure 3A shows the preoperative CTA of the left lower pulmonary vein, which shows that the opening of the left lower pulmonary vein is compressed and narrowed, with an inner diameter of about 0.12 cm. Figure 3B shows the postoperative CTA of the left lower pulmonary vein, which shows that the opening of the left lower pulmonary vein is significantly expanded compared to preoperative, with an inner diameter of 0.41 cm
The surgical results of the four patients are listed in Table 1. All four patients successfully stopped extracorporeal circulation, which was maintained by a low-dose dopamine mixture and milrinone, and had stable circulation. During shutdown, both pulmonary artery pressure and RVP significantly decrease.
Table 1Surgical related data of four patientsPatient 1Patient 2Patient 3Patient 4AMS-ABP (mmHg)85/55(67)64/44(50)61/40(50)81/52(63)AMS-RVP (mmHg)86/6(48)67/3(31)20/5(14)55/4(29)SECM-ABP (mmHg)67/42(51)82/45(59)61/40(50)69/43(52)SECM-RVP (mmHg)29/1(14)30/−2(10)26/−1(13)27/−1(13)CPB time (mins)247120107129Aortic occlusion time (mins)179766178Ventilator assistance time (hours)2151922ABP: Arterial blood pressure; RVP: Right ventricular pressure; AMS: After median sternotomy; SECM: Stopping the extracorporeal circulation machine
Postoperative echocardiography in the first patient showed a reduction in the diameters of the right atrium and right ventricle compared to preoperative measurements, along with mild tricuspid regurgitation and a left lower pulmonary vein flow velocity of 57 cm/s. The entire course of the left lower pulmonary vein was unobstructed and without stenosis. Right‑heart catheterization performed without supplemental oxygen yielded a mean pulmonary artery pressure of 18 mmHg and a total pulmonary resistance of 8.6 Wood units × m². Left lower pulmonary artery angiography demonstrated that the left lower pulmonary vein was wider than preoperatively, with proximal and distal diameters of approximately 5.5 mm (Fig. 1). CT confirmed widening of the left lower pulmonary vein compared to the preoperative scan (Fig. 1).
In the second patient, echocardiography revealed a significant decrease in the diameters of the right atrium and right ventricle compared to preoperative values, with mild tricuspid regurgitation and a left lower pulmonary vein flow velocity of 60 cm/s. The entire course of the left lower pulmonary vein was unobstructed and without stenosis. Right‑heart catheterization without supplemental oxygen showed a mean pulmonary artery pressure of 12 mmHg and a total pulmonary resistance of 9.1 Wood units × m².
In the third patient, echocardiography showed a significant decrease in the diameters of the right atrium and right ventricle compared to preoperative measurements, with mild tricuspid regurgitation. The flow velocity in the left lower pulmonary vein was 52 cm/s. The entire course of the left lower pulmonary vein was unobstructed and without stenosis. Right‑heart catheterization without supplemental oxygen yielded a mean pulmonary artery pressure of 14 mmHg and a total pulmonary resistance of 13.9 Wood units × m².
In the fourth patient, echocardiography demonstrated a significant decrease in the size of all cardiac chambers compared to preoperative findings, with mild tricuspid regurgitation. The left lower pulmonary vein had a flow velocity of 80 cm/s and a diameter of 3.2 mm. The entire course of the left lower pulmonary vein was unobstructed and without stenosis. CT showed widening of the left lower pulmonary vein compared to the preoperative scan (Fig. 3).
Pulmonary arterial hypertension (PAH) is a rare disease in infants and children that is associated with significant morbidity and mortality. PAH is characterized by progressive pulmonary vascular functional and structural changes resulting in increased pulmonary vascular resistance and eventual right-heart failure and death. In many pediatric patients, PAH is idiopathic or associated with congenital heart disease and is rarely associated with other conditions [12]. Idiopathic pulmonary hypertension occurs in patients with no underlying disease known to be associated with PAH, and it is currently mostly treated conservatively in the clinic [13, 14]. Although intervention and surgery can use the atrial septal foramen and Potts shunting to prolong survival time [15, 16], the prognosis of patients has not significantly improved due to the lack of detection and resolution of the pathogenic cause. Clinically, in children with congenital heart disease who suffer from complete or partial anomalous pulmonary venous connections [17], pulmonary vein stenosis after surgery often leads to the progressive development of pulmonary arterial hypertension. Therefore, some “idiopathic” pulmonary hypertension might be caused by stenosis of a single pulmonary vein. When left lower pulmonary vein stenosis is present clinically, echocardiography often falls short in providing a precise diagnosis, and cardiac CT has limitations in detecting PAVMs, particularly smaller or complex lesions, due to resolution issues, with patient motion and contrast media also potentially affecting image quality, necessitating a combination of imaging modalities for accurate diagnosis. If there is no apparent stenosis at the left atrial opening, a missed diagnosis often occurs, and only evident stenosis is indicated. These results affect patient diagnosis by clinicians. It is believed that there is no surgical indication for severely underdeveloped pulmonary veins, which leads to the initiation of conservative or surgical shunt treatment in internal medicine, and the opportunity for surgical cure is missed.
In our study, among the four patients we treated, no left lower pulmonary vein stenosis was found on echocardiography, and all the patients were characterized by severe pulmonary arterial hypertension and left ventricular compression. Two patients also had a minor atrial septal defect or ventricular septal defect, respectively. When further exploring the causes of pulmonary arterial hypertension, CT scans of all patients revealed that the left lower pulmonary vein entering the left atrial opening was closer to the spine in these patients than in patients with congenital heart disease without pulmonary arterial hypertension. The position of the left lower pulmonary vein originating from the pulmonary hilum was significantly lower than that of the descending aorta, and its shape was compressed by the descending aorta, forming a certain angle. Especially in the third patient, the left lower pulmonary vein approached 90 degrees at the descending aorta. Considering the location of the pulmonary hilum, it presented an exhibited “S” shape throughout the entire process, causing severe stenosis and obstructing pulmonary venous return, resulting in reduced blood flow and CT showing excellent pulmonary veins with severe hypoplasia. Intraoperative exploration revealed that all the pulmonary veins in the four patients were not narrowed, with smooth intima and sound development. This further confirmed that the CT scan revealed extremely fine and poorly developed pulmonary veins due to compression and deformation of the descending aorta, resulting in a significant decrease in blood flow inside the pulmonary veins. Although selective pulmonary angiography revealed 60% stenosis at the entrance of the right lower pulmonary vein in the third patient before surgery, the adjacent tissue did not cause compression. No abnormalities were found during intraoperative exploration, suggesting that the relative stenosis was caused by physiological structural distortion.
This study is limited by its retrospective nature and small sample size. As a case series, it focuses on the clinical course of four specific patients rather than establishing the epidemiological prevalence of LLPVC in the general PAH population. Consequently, data regarding the total incidence of LLPVC among all PAH patients during the study period were not available for analysis.
The first patient underwent surgery using widening patches at the left atrial opening and pulmonary vein trunk. At that time, there was no clear understanding of pulmonary vein compression. After exploring the pulmonary vein opening and trunk, it was expected. It was considered that the position of the pulmonary vein opening was abnormal and more inclined toward the spine, possibly due to pulmonary vein obstruction caused by distortion and deformation of the opening, and no consideration was given to descending aorta compression. Therefore, only autologous pericardium was used for widening patches. Although the postoperative pressure immediately decreased to normal, only partial improvement was observed on CT and angiography. The width of the compressed area on CT increased from 1.7 mm to 3.2 mm, and the width on angiography increased from 3.8 mm to 5.5 mm. However, there was still an angle at the descending aorta. After summarizing the first patient, the second, third, and fourth patients were treated with an opening of the left lower pulmonary vein for re-transplantation, which completely relieved the compression of the descending aorta and achieved better results.
RVP catheters were placed before surgery in the second, third, and fourth patients. In the third patient, the RVP was not elevated after median sternotomy, measuring 20/5 (14) mmHg. This may be because the thoracotomy significantly relieves the pressure exerted on the sternum and pericardium by the enlarged right heart system, which in turn relieves the pressure on the left lower pulmonary vein located directly behind it. Additionally, the pressure on the descending aorta was relatively low at 61/40 (50) mmHg during median sternotomy, which was further relieved. Of course, it cannot be ruled out that the left lower pulmonary vein was compressed and pulled and reflexively caused a spasm of the anterior capillary artery. After deep anesthesia, the spasm was relieved, resulting in a decreased in RVP.
In this study, three patients underwent preoperative right-heart catheterization due to severe elevation of pulmonary artery pressure, and oxygen inhalation began immediately upon admission. After oxygen inhalation, the overall lung resistance was significantly more significant than the surgical indications for concomitant congenital heart disease and pulmonary arterial hypertension [17]. Previous studies have suggested that patients with pulmonary hypertension with concomitant congenital heart disease should have a total pulmonary resistance greater than 4.6 WU or a pulmonary artery resistance index greater than 8 WU⋅ m^2^ as surgical contraindications [18]. Due to the presence of an atrial septal defect in the first patient and a CT report of stenosis of the left lower pulmonary vein opening, severe pulmonary arterial hypertension in the patient was considered to have been caused by stenosis of one pulmonary vein opening. Therefore, it was thought that relieving the opening stenosis may reduce the patient’s pulmonary artery pressure, and surgical treatment was needed. After the patient stopped extracorporeal circulation, the pulmonary artery pressure immediately decreased and gradually approached normal levels when the chest was closed. This indicates that idiopathic pulmonary hypertension caused by left lower pulmonary vein stenosis may mainly be due to mechanical obstruction or reflex pulmonary arteriolar spasm. Various cytokines released by the body’s endocrine system and secondary plexiform degeneration of the pulmonary vascular bed do not play a significant role in the early stages of this disease, laying a theoretical foundation for seeking a cure for this type of “idiopathic” pulmonary hypertension. Based on our experience of treating the first patient, we completed the surgical treatment of the following two patients and achieved good surgical results. The tracheal tube was removed within 24 h after surgery for all three patients, and the pulmonary artery pressure decreased to normal levels.
Our research revealed that if infants or children experience unexplained resistance-type pulmonary hypertension or progressive elevation of pulmonary artery pressure after surgery for congenital heart disease in the early stage, routine cardiac computed tomography angiography (CTA) should be performed to rule out left lower pulmonary vein compression and prevent missed diagnoses.
The four patients did not receive targeted medication for pulmonary arterial hypertension after surgery and recovered smoothly without any surgical complications. The patients were discharged typically and were confirmed to have normal pulmonary arterial pressure by echocardiography at discharge. These results confirm that surgery can completely correct this type of pulmonary arterial hypertension. Although further observation is needed to obtain long-term results, this study provides novel ideas for the radical treatment of some cases of idiopathic pulmonary hypertension.
There were several limitations in our study. First, the number of patients included in this study was small. Therefore, this study can only demonstrate our limited experience with treating left lower pulmonary vein stenosis caused by compression of the descending aorta. Second, the follow-up time was relatively short, and some follow-up data were incomplete. In the future, we will conduct a large clinical prospective study to investigate further the relationship between pulmonary vein stenosis caused by compression of the descending aorta on the left lower pulmonary vein and pulmonary arterial hypertension and the effectiveness of surgical treatment.
While pediatric pulmonary arterial hypertension (PAH) shares characteristics with the adult form of the disease, it is often associated with additional comorbid conditions and clinical challenges that necessitate distinct management strategies. Pulmonary vein stenosis (PVS), which carries a poor prognosis, can complicate the disease course and is increasingly recognized as an important cause of persistent pulmonary hypertension. We described four pediatric cases in which PAH was likely induced by pulmonary vein stenosis. All four patients subsequently underwent surgical intervention. Upon mobilization of the left lower pulmonary vein, no intrinsic stenosis was observed in its trunk or at the left atrial orifice. Instead, compression by the descending aorta was identified. Postoperatively, pulmonary arterial pressure normalized in all cases. Therefore, this study may offer a novel perspective on a potentially curative surgical approach for a subset of patients with idiopathic pulmonary hypertension.