**6. Anomalous pulmonary venous connection**

Another important developmental abnormality of pulmonary vein is the anomalous pulmonary venous connection. In human medicine, the TAPVC was comprised of 1–5% congenital heart diseases cases [36] and 0.6 to 1.2 per 10,000 live births [37]. The PAPVC was found 0.4% to 0.7% in the routine autopsies [38, 39]. A retrospective study that reviewed 290 dogs with cardiovascular malformations from 1953 to 1965 revealed that only 1 case was diagnosed PAPVC with secundum atrial septal defect [40]. For the published case reports, there are only 3 dogs [41–43] and each 1 of chicken [44] and foal [45] that are diagnosed as TAPVC; only 4 dogs [46–48] and 2 cats [49, 50] are PAPVC. One canine case reported in 1975 did not describe its detail (TAPVC or PAPVC) [51].

As previous discussed, the primitive pulmonary veins from the lung buds develop from the splanchnic plexus, which communicates with the systemic venous system, and connects to the left atrium. As development proceeds, the connection between pulmonary veins and the systemic venous system disappears. If the communication between pulmonary veins and the systemic venous system persists, TAPVC or PAPVC would be diagnosed depending on the degree of persistent connections [8].

The TAPVC is that all pulmonary veins being abnormally connected to the systemic venous circulation, that is, the right atrium would receive both systemic and pulmonary venous return. Researchers had described four types of TAPVC depending on the connection level (**Figure 3**). Type I, or supra-cardiac type, is the most common type that consist 40–55% of cases. The pulmonary veins empty through left innominate vein, superior vena cava or azygos veins. Type II, or cardiac type, is the second common type that consist 15–30% of cases. The pulmonary veins drain into the right atrium through the coronary sinus or in the posterior wall of the right atrium. Type III, or infra-cardiac type, is accounting approximately 15–26% of cases. The pulmonary veins run to the portal venous system or inferior vena cava. And type IV, or mixed type, is representing 2–10% cases that there are at least two different drainage sites [52, 53].

#### **Figure 3.**

*The classification of TAPVR. Type I, the Supra-cardiac type; Type II, the cardiac type; Type III, the infra-cardiac type, and the Type IV, the mixed type. CaVC, caudal vena cava; CrVC, cranial vena cava; PA, pulmonary artery; PV, pulmonary vein; RA, right atrium.*

In the setting of TAPVC, a right-to left shunt via an atrial septal defect (ASD), patent foramen ovale (PFO) or to a lesser extent of patent ductus arteriosus is required for completing circulation and maintaining life [54]. The presence of right (pulmonary) to left (systemic) shunting permits mixture of oxygenated and deoxygenated blood to enter the systemic circulation. Signs of dyspnea with exertion, cyanosis and exercise intolerance could be observed, and the patient is at risk of developing to pulmonary hypertension and congestive heart failure. Three veterinary cases were found to have concurrent ASD (secundum type in 1 dog [41] and 1 chicken [44]; sinus venous type in another dog [42]) and the case of foal [45] had concurrent PFO. A special child case had been recognized recently that all of his pulmonary veins

were anatomically connected to the left atrium but the blood inside actually was drained into superior vena cava via an innominate vein, therefore corresponded to the definition of supra-cardiac type of anomaly [35].

Thoracic radiography is commonly the first imaging exam, it can be normal or some classic changes may exist depending on the types of abnormal connections. A snowman sign has been described in patients with supra-cardiac TAPVC. The head is formed by superior vena cava, vertical vein (common vein that formed by the four anomalous pulmonary veins) and innominate vein, and the body is formed by enlarged right atrium. Another famous radiographic characteristic is the scimitar signs in the PAPVC. It describes the anomalous pulmonary veins like a sword with a curved blade that mostly affect the right-side lung lobes [5, 55].

In addition, the clinical utility of echocardiography in diagnosing abnormalities of pulmonary venous connection is somewhat difficult because of limited echo window, but it can provide the information of the concurrent congenital cardiac anomalies and hemodynamic consequences like the dilated right heart or possible pulmonary hypertension. Transesophageal echocardiography has the advantage that it can access from the heart base aspect, therefore providing more clear images of the structures near the heart base. Right heart catherization can opacify the right heart chambers and venous vasculature but is limited that some small accessory and anomalous vessels may be missed.

For obtaining the full picture of abnormal development of pulmonary veins, multidetector computed tomography and magnetic resonance imaging both can provide good images. The importance of advanced imaging modules in diagnosing these complex cardiovascular developmental diseases had been emphasized in these years [49, 50]. Both of multidetector computed tomography and magnetic resonance imaging are non-invasive, and they can offer multiplanar and three-dimensional reconstructive model. Small lesions and details can be further illustrated by contrast median. Lack of ionizing radiation is the advantage of magnetic resonance imaging, but this procedure needs longer time and sedation which may be risky in some patients [53].

Generally, surgical repair is recommended at the time that TAPVC is diagnosed [56]. The surgical outcome is acceptable with the 6.6% of intraoperative and late death and 15% of recurrent pulmonary venous obstruction in the survivors. Risk factors for both undesired consequences including preoperative pulmonary venous obstruction, infra-cardiac type and mixed type [57]. This result emphasizes the importance of pre- and intra-operative assessment.

Partial anomalous pulmonary venous connection refers to equal to or more than 1, but not all, pulmonary veins being connected to the systemic venous circulation rather than the left atrium. Affected animals can exhibit no clinical signs or have symptoms associates with congestive heart failure and pulmonary hypertension. In the total of 6 veterinary cases, half of them were asymptomatic (2 miniature schnauzers [46] and 1 Devon Rex cat [49]) and the other half were presented with signs of decompensation (exercise intolerance in 1 Belgian Malinois dog [47], pulmonary edema in 1 toy poodle [48] and 1 American shorthair kitten [50]). The severity of symptoms depends on the number of affected pulmonary veins, that is, the degree of left-to-right shunt. A ratio of pulmonary to systemic blood flow (Qp:Qs) can be used to estimate the magnitude of left-to-right shunt, and the ratio greater than 1.5 to 2 is generally considered hemodynamic significant because the patient is at risk of pulmonary hypertension and heart failure, and surgical treatment is usually recommended in these cases [58].

According to the affected pulmonary veins, as many as 27 different anatomic variations had been proposed [59]. The characteristic of partial APVR in pediatric and adult populations varies significantly. In a prospective survey of pediatric patients, mostly (90%) were right-sided and in association of sinus venosus atrial septal defect [60]. In other two retrospective study that focused on adult (>18 years old), abnormal development of pulmonary vein from the left upper lobe was the most (ranging from 47–79%), followed by the right upper pulmonary vein (ranging from 17–38%) [61, 62]. The human patients that were diagnosed in childhood were mostly symptomatic, and those that diagnosed until adulthood were usually an incidental finding. Related signs including dyspnea, orthopnea, fatigue, chest pain, palpitations, tachycardia, and peripheral edema [53].

Surgical repair of the PAPVC with different strategies (intracardiac baffle, pulmonary vein implantation, or superior vena cava division with reimplantation on the right atrial appendage) in children showed excellent outcomes [60]. In a case series that only contain adult patients (20 to 66 years old), conservative management with close monitoring is recommended in asymptomatic patients, and the surgical outcomes in symptomatic patients are usually excellent with low complication rate [63]. Sinus node dysfunction and postoperative venous stenosis are the possible consequences followed surgery [64]. In a recent canine case, his PAPVC and sinus venosus ASD were successfully repaired by single-patch method under cardiopulmonary bypass. The patient remained stable and free of clinical signs in the following one year, suggesting that this is a valid treatment option for other similar case [48].

We can find that the terms of "connection", "drainage" and "return" are all used in the literature to describe the abnormality. The "connection" indicates an anomalous venoatrial connection, whereas the word "drainage" or "return" describe the concept of abnormal pulmonary venous return despite normal anatomical connection [65]. Appropriate wording should be applied depending on the individual case. By reviewing veterinary literature, the clinical manifestation of TAPVC or PAPVC can vary depending on the individual. Owing to the scarcity of these diseases, we still know little about them. Future reports, including studies before and after death, treatment options and related outcome, are warrant.
