Shunting Between the CVC and Both the Azygos Vein and Thoracic Duct in a Dog with CTD^S

Introduction

Cor triatriatum dexter (CTD) is a well-documented congenital heart defect in dogs; however, its overall prevalence is low, with only 21 reports to date.^1–10 In CTD, the right atrium is partitioned into a cranial and a caudal chamber by a remnant embryologic right sinus venosus valve. That membrane is usually perforated, and the pressure gradient between the two atrial chambers depends on the diameter of the opening. Only the communication of the cranial chamber with the right ventricle is unimpeded. As a result, higher pressure is recorded in the caudal chamber, which drains the caudal vena cava (CVC). In CTD, blood cannot flow normally out of the liver, and flow reversal into the hepatic vessels occurs during atrial systole.⁹ This relative obstruction of the venous flow between the liver and the right atrium results in postsinusoidal portal hypertension and Budd-Chiari-like syndrome. The associated diagnostic findings include hepatomegaly, distended hepatic veins, a distended CVC, and ascites containing > 25 g/L of protein. If the defect is left untreated, cachexia and exercise intolerance can ensue. There has been only one reported case of an asymptomatic dog with CTD.² In dogs, CTD is sometimes associated with other severe malformations.^1,5,6,9,10 This is the first case report documenting CTD associated with shunting between the CVC and both the azygos vein and thoracic duct in a dog.

Case Report

A 5 mo old female rottweiler weighing 9.5 kg was referred to the Cardiology Service of the Department of Companion Animals, Veterinary Campus of Lyon, France for evaluation of a suspected congenital heart disease. The dog had been evaluated by the referring veterinarian 5 days prior to referral for a 4 day history of anorexia and exercise intolerance. The owners reported that the dog had always been smaller than her littermates. The referring veterinarian found weak femoral pulses, severe dyspnea associated with a large volume of pleural effusion, and marked abdominal distension secondary to ascites. Treatment with furosemide^a (2 mg/kg per os [PO] q 12 hr) and spironolactone^b (2 mg/kg PO q 24 hr) resulted in temporary improvement.

At the time of referral, dyspnea was noted and the dog was slightly lethargic. The mucous membranes were pale, the heart rate was 100 beats/min, and the femoral pulses were weak. Systolic arterial blood pressure, measured by Doppler, was 110 mm Hg. Lung sounds were increased in the caudodorsal quadrants of the chest, and the abdomen was mildly distended with a palpable fluid wave.

The presence of pleural and abdominal effusion was verified with a brief ultrasonographic examination; however, the amount of pleural fluid was too small to sample. Thoracic radiographs revealed an alveolar pattern and small middle and caudal right pulmonary lobes, consistent with either atelectasis or lung lobe torsion. The intrathoracic CVC was dilated.

Straw-colored fluid was collected from the abdomen. Cytology was consistent with a modified transudate containing 2,000 cells/mm³ (reference range, 0–5.10 ^ 9/L), including 61% neutrophils, 21% macrophages, 13% lymphocytes, and 5% eosinophils. The protein content was 40 g/L (reference range, < 25 g/L). Postsinusoidal portal hypertension was suspected.

Based on the young age of the dog, exercise intolerance, severe loss of body condition (body condition score was 1/5), presence of the modified transudate in the abdomen, and dilatation of the intrathoracic CVC, an obstacle to venous return from the CVC to the right atrium was suspected, and an echocardiography was performed. As illustrated in Figure 1, the right atrium was divided by a membrane into a caudal (accessory right atrial chamber or sinus venarum) and a cranial chamber (the true right atrium). A small defect in the membrane allowed blood to flow from the caudal chamber to the cranial chamber, and a continuous turbulent flow between the two chambers was recorded by continuous-wave Doppler (maximum velocity was 2.30 m/sec, which corresponded to a peak diastolic pressure gradient of 21 mm Hg). The coronary sinus was dilated. Based on those findings, CTD was diagnosed. To better characterize the defect, a contrast echocardiography was performed using agitated saline^c successively injected into the right cephalic and saphenous veins. Microbubbles injected into the cephalic vein drained normally first into the cranial vena cava then the cranial chamber of the right atrium, which communicated with the right ventricle. No contrast was noted in either of the atrial chambers when the saline was injected into the saphenous vein.

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Computerized tomography angiography (CTA) centered on the thorax confirmed the suspected CTD, showing hepatomegaly with distended hepatic veins, marked distention of the CVC and azygos vein, and a tortuous thoracic duct. The azygos vein drained into the cranial chamber of the right atrium. Mild pleural effusion was also visible on the CTA, and a right middle lung lobe torsion was highly suspected based on its alveolar density, the abnormal location of the airway, and the tapering of the bronchus, which was twisted.

Abdominal ultrasonography revealed a mild amount of free peritoneal fluid, marked generalized hepatomegaly, and markedly distended hepatic veins. Color Doppler ultrasonography detected a retrograde pulsatile flow in the portion of the CVC to the liver but cranial to the phrenicoabdominal veins. A large vessel was identified arising from that portion of the CVC, which travelled toward the spine where it most likely connected to the azygos vein based on its localization (Figures 2,3). Another tortuous abnormal vessel was connected to the distal part of the CVC cranial to the iliac veins. That second tortuous vessel ran in a dorsal direction toward the diaphragm. A second contrast ultrasonography from the right saphenous vein was performed, which confirmed the communication between the CVC and both the right azygos vein (see Supplementary Video I) and the tortuous abdominal vessel.

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Because the CTA only imaged the thorax, it did not allow precise characterization of the abdominal vascular abnormalities. An angiography was therefore performed. A nonionic iodinated contrast agent^d (1 mL/kg) was injected into the right lateral saphenous vein. The nonselective venogram confirmed flow from the distal part of the CVC through a small tortuous abnormal vessel (Figure 4). That vessel extended in a long, tortuous dorsocranial direction, crossing the diaphragm and running on the dorsal border of the thoracic aorta and the ventral border of the azygos vein to the level of the sixth thoracic vertebra. It terminated in the cranial mediastinum, probably emptying in the cranial vena cava. Its size, shape, location, and course on ultrasonography, angiography, and CTA were suggestive of the thoracic duct Despite the anomalous abdominal path and origin were anomalous.

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The final diagnosis was a CTD associated with shunts between the CVC and both the azygos vein and thoracic duct. Because the dog’s mucous membranes were pale and general anesthesia for surgery was considered, blood work and a urinalysis were performed. Urinalysis was unremarkable. Biochemical abnormalities included mild hypokalemia (3.4 mmol/L; reference range, 3.6–5.6 mmol/L) and elevated C-reactive protein (22 mg/L; reference range, 0–10 mg/L). Albumin was normal 28 g/L (reference range, 27–38 g/L) but alkaline phosphatase was mildly elevated (150 UI/L; reference range, 10–60 UI/L). The complete blood cell count revealed a moderate, microcytic, normochromic, regenerative anemia. Hemoglobin was 89 g/L (reference range, 120–180 g/L), hematocrit was 27% (reference range, 37–54%), reticulocyte count was 480,000/mm³ (reference range, < 80,000/mm³), mean corpuscular volume was 61 fL (reference range, 60–77 fL), mean corpuscular hemoglobin was 20 pg (reference range, 17–23 pg), and mean corpuscular hemoglobin concentration was 32.5 g/dL (reference range, 31–36 g/dL). A moderate leukocytosis (25.9 × 10 ^ 9/L; reference range, 6–17 × 10 ^ 9/L) with neutrophilia (21.5 × 10 ^ 9/L; reference range, 3.9–12 × 10 ^ 9/L) and marked thrombocytosis (1.010 × 10 ^ 9/L; reference range, 200–500 × 10 ^ 9/L). Blood smear examination confirmed those abnormalities, and a few spherocytes and schizocytes were observed. A direct Coombs’ test was negative. Microcytic anemia in association with marked thrombocytosis led to the suspicion of either a functional or absolute iron deficiency, which was confirmed by a low serum iron concentration (37 μmol/L; reference range, 60–230 μmol/L). Total iron binding capacity was normal (54 μmol/L; reference range, 44–107 μmol/L). Fecal examination excluded intestinal parasites as a cause of digestive bleeding.

The dog was treated with furosemide (4 mg/kg PO q 8 hr), spironolactone (2 mg/kg PO q 24 hr), and ferrous fumarate^e (7 mg/kg PO q 24 hr). The anemia, ascites, and respiratory signs resolved with medical treatment, and the dog gained body condition. Surgical treatment of the CTD and lung lobe torsion was discussed but the owners elected to postpone surgery because the respiratory signs had resolved and the dog was in good body condition. The owners were also worried about the risk of surgery despite the possible long-term negative effects of the shunts. The dog continued to do well after several months, and the owners eventually opted for surgery. The patient underwent right atrial membrane resection with venous inflow occlusion. A tortuous vessel, which most likely contained lymph, was visualized dorsally to the heart, and was identified as the thoracic duct. The middle right lung lobe was heterogeneous and smaller than usual. The macroscopic lesions of the middle right lung lobe were compatible with an old lobe torsion (Figure 5). A lobectomy was considered, but because the lung partially retained normal color upon insufflation and considering the dog was asymptomatic before surgery, the lobe was not removed.

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The dog recovered uneventfully. Contrast ultrasonography and color Doppler ultrasonography performed the day after surgery confirmed the absence of retrograde blood flow in the CVC. The patient was discharged 4 days postsurgically with cephalexin^f (15 mg/kg PO q 12 hr for 7 days) in addition to the medical treatment described previously. Clopidogrel bisulfate^g (2 mg/kg PO q 24 hr for 3 wk) was prescribed to prevent thrombus formation after intracardiac surgery. Two wk later, the dog appeared much more active. Eleven mo after surgery, all medical treatments had been stopped, and the dog was growing, acting normally, and had normal exercise tolerance.

Discussion

Concurrent cardiovascular abnormalities previously described with CTD include incomplete persistent left cranial vena cava, Ebstein’s anomaly, tricuspid valve dysplasia, dynamic subaortic stenosis, atrial septal defect, pulmonic valvular stenosis, and ventricular septal defect.^1,5,6,9,10 To the authors’ knowledge, this is the first reported case of CTD associated with shunts between the CVC and both the azygos vein and the thoracic duct in a dog.

Szatmari et al. (2000) reported the first case of retrograde pulsatile flow in the CVC in a puppy with CTD.⁹ The nonselective venogram demonstrated that blood from the CVC flowed through the dilated lumbar veins into the ventral internal vertebral plexus and through an anastomosis between the lumbar and azygos veins into the right azygos vein. In the case described herein, the angiography did not identify blood flow from the CVC into the ventral internal vertebral plexus. Instead, color Doppler and contrast ultrasonography demonstrated a retrograde pulsatile flow in the CVC and a continuous blood flow from the CVC into the dilated right azygos vein through an abnormal vessel. A similar caudal venogram can be seen when blood flow in the CVC is either compromised (as shown in dogs with CTD and subsequent retrograde flow in the CVC) or in cases of acquired or congenital obstruction, stenosis, or kinking of the CVC.^4,8,11

Several dogs with CTD had evident collateral circulation from the CVC into the azygos vein, but the origin of this anastomosis remains unclear.^4–6,8 Hunt et al. (1992) and more recently Fischetti and Kovak (2008) described a congenital interruption of the prehepatic CVC with continuation as the azygos vein.^12,13 During normal development, there is a continuity between the embryonic CVC and azygos vein, which ceases with regression of the intervening segment of the supracardinal vein. Improper completion of the developmental process may results in CVC interruption.^12,13 The necessity for blood from the caudal part of the embryo to return to the heart presumably results in persistence of the middle portion of the supracardinal vein, resulting in the CVC continuing as the azygos vein. The high pressure in the CVC preventing normal flow back to the right heart caused by the CTD in this case report could have mimicked CVC interruption and caused a persistent anastomosis with the azygos vein.

The postsinusoidal portal hypertension most likely caused the proteinaceous ascites. The fact that the CVC was distended presurgically and the ascites resolved with surgical removal of the intra-atrial septum further supports this conclusion. Abdominal distension due to ascites has been the presenting sign of almost all reported canine cases of CTD. The origin for pleural effusion is more questionable and may be due to the increased hydrostatic pressure in the azygos vein, the lung lobe torsion, or both. The azygos vein normally originates in the dorsal thoracolumbar region and travels cranially through the dorsal thorax, transmitting blood from the posterior walls of the thorax (vertebrae, ribs, and related structures), abdomen, and hind limbs to the cranial vena cava and the right atrium. In some cases, the azygos vein can go directly to the right atrium.¹³ The anatomy of the azygos vein can be quite variable. In this case, the marked distension of the azygos vein was probably secondary to the abnormal route and volume of blood flowing from the CVC through the shunt. This was suspected to cause increased hydrostatic pressure. Interestingly, pleural effusion, hepatomegaly, and ascites also have been reported in association with a fibroma that obstructed blood flow from the CVC into the right atrium and in a membranous obstruction of the CVC at the cavoatrial junction.^14,15 There was no hypothesis concerning the physiologic basis for the pleural effusion observed in those two dogs. The highly suspected lung lobe torsion in the case described above may also have occurred secondary to the presence of pleural effusion.

Concerning the origin of the shunt between the CVC and the thoracic duct identified in this dog, it may be hypothesized that one of the original connections between the venous and the lymphatic system that are described in the embryo may have been retained in this dog. In humans, there has been a number of articles on lymphovenous anastomosis, but few reports of the opposite situation (i.e., venolymphatic communication).¹⁶ Only one case has been reported in dogs. In that study, Danese et al. (1962) noted an aberrant venolymphatic communication in a dog during postmortem lymphangiography of the hind limbs. The contrast medium freely passed from the popliteal node into the femoral vein.¹⁷ The small diameter and tortuous path of the vessel identified in the dog describe in this case report could favor stasis, which is one of the three broad categories of factors called Virchow’s triad that are thought to contribute to thrombosis. However, clinical significance of this vessel remains unclear and the usefulness of a second surgery to close this shunt is open for discussion.

The association of the three described cardiovascular defects in this dog had hematologic consequences. Anemia is commonly diagnosed, but not clearly explained, in reports of dogs with CTD. Most of the time, a mild, microcytic, hypochromic, regenerative anemia is noted.⁹ In this case, a decreased red cell count and high reticulocyte count were observed. The presence of moderate anisocytosis and polychromatophilia on the blood smear examination confirmed a regenerative anemia. The high reticulocyte count and moderate anisocytosis, with normal mean corpuscular volume, underlined the presence of microcytosis.¹⁸ Decreased serum iron concentration and good response to iron supplementation confirmed the suspected iron deficiency. Marked thrombocytosis is also commonly associated with either a functional or absolute iron deficiency anemia.

Functional iron deficiency has been associated with the anemia of inflammatory diseases and portosystemic shunts.¹⁸ In our case, the high reactive protein C level and moderate leukocytosis may reflect an inflammatory state secondary to chronic ascites and pleural effusion, but the regenerative nature of anemia in this case did not suggest inflammation as the cause of anemia. In young dogs with low iron storage and congenital portosystemic shunts, iron sequestration or ineffective iron transport have been proposed as causes for iron-deficient erythropoiesis.^19,20 In our case, total serum bile acids concentrations could have been interesting to investigate liver function and a possible decreased iron metabolism. Serum total alkaline phosphatase activity was increased and could be related to high isoenzyme of bone origin level in a growing puppy.

Extravascular or intravascular blood losses are commonly implicated in absolute iron deficiency. Digestive bleeding (for instance in case of parasitism) is unlikely in this case. A few schizocytes on blood smear examination may emphasize intravascular hemolysis.¹⁸ Caval syndrome linked with heartworms in the CVC and right atrium is commonly implicated in this phenomenon. In this case, the CTD may have produced a similar effect due to the turbulence in the CVC and right atrium, which may generate red blood cell trauma. Intravascular hemolysis, inflammatory state, low storage iron and abnormal iron metabolism may altogether have participated to anemia.

Conclusion

CTD is a congenital heart defect usually associated with serious hemodynamic consequences in dogs. Surgical treatment is therefore indicated in most cases. This report emphasizes the importance of presurgical assessment of concurrent thoracic and abdominal congenital vascular abnormalities.