Suspected Iatrogenic Paradoxical Embolization in a Cat

Introduction

Currently in veterinary medicine, there are no published reports that objectively assess the overall complication rate of cardiac catheterization; however, the incidence in human cardiology ranges from 1.9% to 3.6% for all catheterization procedures.^1,2 Thromboembolic events are some of the more common complications that lead to a variety of adverse clinical signs. The incidence of thromboembolic complications in human cardiology has ranged from 0.9% in early studies to 0.18% in more recent studies.^1,3 While the majority of these occurrences represent local thrombus formation at the site of vascular access and subsequent embolic showering resulting in decreased local blood flow, numerous other thromboembolic complications can arise. These include, but are not limited to, myocardial infarction, pulmonary thromboembolism, and cere-brovascular accidents. Iatrogenic paradoxical embolization has also been reported in the human literature.^1,4,5

Paradoxical embolization is a term that was first used in the 19th century to describe a condition in which thromboemboli derived from the systemic venous system reached the systemic arterial system via an abnormal intracardiac communication.⁶ In human medicine, it is a well-recognized complication of right-to-left shunting defects and is most often diagnosed only at necropsy.^7,8 There are, however, numerous reports of antemortem diagnoses of paradoxical embolization and impending paradoxical embolization.^8,9 To the authors’ knowledge, no reports of such cases exist in the veterinary literature. The purpose of this report is to describe apparent paradoxical embolization in a cat secondary to cardiac catheterization.

Case Report

A 4.3-kg, castrated male, domestic shorthair cat of at least 5 years of age was referred to the Purdue University Veterinary Teaching Hospital (PUVTH) with a 5-year history of episodic, exercise-induced cyanosis and panting that had progressed in frequency and severity. Evidence of right-sided heart failure (i.e., ascites) was also present. The referring veterinarian had detected a heart murmur on auscultation and cardiomegaly on thoracic radiography. Treatment prior to presentation consisted of digoxin^a (0.01 mg/kg orally q 12 hours), which resulted in fewer episodes. Immediately prior to presentation, the cat had an acute episode of dyspnea that was treated with furosemide^b (2 mg/kg intravenously [IV]); an abdominocentesis was performed for the ascites, and oxygen was administered.

Physical examination revealed a cat in good body condition (body condition score of 3/5) with a grade III/VI systolic murmur over the left parasternal border, occasional pulse deficits, jugular venous distension, a mild amount of ascites, and mild resting dyspnea. Minimal restraint resulted in severe dyspnea and cyanosis, consistent with right-to-left cardiovascular shunting (e.g., tetralogy of Fallot, Eisenmenger’s syndrome, reverse patent ductus arteriosus).

Sinus tachycardia with occasional ventricular premature complexes and evidence of right ventricular enlargement were seen on electrocardiography. Thoracic radiography demonstrated marked right ventricular and right atrial enlargement, reduced pulmonary vascular markings, and enlargement of the ascending aorta and caudal vena cava. Two-dimensional echocardiography revealed a large, peri-membranous ventricular septal defect (VSD); dextrapositioned aorta; concentric hypertrophy of the right ventricle; and severe right atrial dilatation [Figures 1, 2]. The right ventricular outflow tract appeared severely hypoplastic and could not be confirmed to be continuous with the pulmonary artery. A small, high-velocity jet within the right ventricular outflow tract, as well as bi-directional shunting across the VSD and mild tricuspid insufficiency, were noted on color-flow Doppler echocardiography. A spectral-Doppler study demonstrated normal aortic forward flows, but pulmonic forward flows could not be obtained. However, the tricuspid regurgitation jet was markedly increased (5.27 meters per second; 111 mm Hg), indicating severely elevated right ventricular systolic pressure. A presumptive diagnosis of tetralogy of Fallot with predominant right-to-left shunting and right-sided heart failure was made.

Diagnostic catheterization was performed to better characterize the anatomy of the right ventricular outflow tract and to assess the defects for possible surgical intervention. Anesthesia was induced with ketamine^c (5 mg/kg IV) and diazepam^d (0.2 mg/kg IV) and was maintained with isoflurane^e in oxygen. Catheterization was performed via the right external carotid artery and external jugular vein. Simultaneous right and left ventricular pressure recordings were made that demonstrated essentially equal pressures (right ventricle: 85 mm Hg systolic, 13 mm Hg diastolic, 46 mm Hg mean; left ventricle: 81 mm Hg systolic, 11 mm Hg diastolic, 42 mm Hg mean). Right ventriculography demonstrated simultaneous opacification of the aorta and pulmonary artery, right ventricular hypertrophy, a moderate amount of right-to-left shunting across the VSD, a severely hypoplastic right ventricular outflow tract and pulmonary artery, and an enlarged ascending aorta that originated predominantly from the right ventricle. Left ventriculography revealed a small amount of left-to-right shunting across the VSD. An increase in bronchoesophageal collateral circulation was seen on ascending aortography.

Recovery from anesthesia was significantly prolonged during the immediate postoperative period. Approximately 36 hours after the procedure, the cat became dyspneic, laterally recumbent, and moribund, with bilaterally dilated pupils, absent pupillary light and palpebral responses, and absent femoral pulses. Cerebral and distal aortic thromboembolization was strongly suggested by these clinical signs, despite the absence of left heart disease. The presumptive diagnosis was paradoxical embolization resulting from the right heart disease and right-to-left shunting, although complications from the left heart study could not be ruled out. Because of the underlying cardiac disease and systemic thromboembolic complications, the owners elected euthanasia, and a necropsy was performed.

Necropsy findings confirmed the diagnosis of tetralogy of Fallot (8 mm × 9 mm VSD, hypoplastic right ventricular outflow tract with infundibular stenosis, dextrapositioned aorta, concentric hypertrophy of the right ventricle), along with a severely hypoplastic pulmonary artery [Figures 3, 4]. The pulmonic valve was severely hypoplastic with failure of separation of the leaflets that resulted in severe valvular pulmonic stenosis. The right atrium and both the cranial and caudal vena cava were severely dilated, consistent with elevated right ventricular filling pressures. Within the right atrium and right ventricle, multiple, large, antemortem thrombi could be seen [Figure 5]. The right subclavian artery had an anomalous origin from the brachycephalic trunk, which may have contributed to the thromboembolus within the closely associated right common carotid artery [Figure 6]. A large thromboembolus was also seen within the aortic trifurcation. When the brain was examined, vascularity was diminished on the entire right side, consistent with a large ischemic vascular accident [Figure 7]. These findings, combined with the thrombi within the right atrium and ventricle, were most consistent with paradoxical embolization that arose secondary to the diagnostic catheterization and concurrent right-to-left shunting. While formation of thrombi within the systemic circulation could have been responsible for the clinical signs, there were no endothelial lesions found within the left atrium, left ventricle, or aorta, and no thrombi were associated with the external carotid arteriotomy.

Discussion

According to the medical literature pertaining to humans, diagnosis of paradoxical embolization requires that four criteria be met: 1) presence of deep venous thrombosis or pulmonary thromboembolism; 2) abnormal communication between the venous and systemic circulation; 3) clinical, angiographic, or pathological evidence of systemic embolism; and 4) the presence of a favorable pressure gradient promoting right-to-left shunting.^8–10 Reports have shown that up to 70% of affected humans have a patent foramen ovale as the main cardiac defect.¹¹ Less frequently associated defects include atrial septal defects with or without Ebstein’s anomaly, VSD, pulmonary arteriovenous malformations, and tetralogy of Fallot.^9,12 Sixty percent of people with paradoxical embolization have symptoms of pulmonary embolization, which leads to an increase in right atrial pressure. Maneuvers that transiently raise right heart pressure account for an additional 15% of paradoxical embolization cases, while only 5% occur in the presence of chronically elevated right heart pressures.¹³

In the cat reported here, the findings of multiple, large right atrial and ventricular thrombi, clinical and pathological evidence of systemic arterial thromboembolism, and the right-to-left shunting physiology of tetralogy of Fallot were consistent with the diagnostic criteria for paradoxical embolization. The diagnostic catheterization most likely caused the formation of thrombi, resulting in iatrogenic paradoxical embolization in this cat. Because both right-and left-sided invasive studies were performed, it is possible that the systemic emboli originated within the systemic circulation secondary to catheter-induced endothelial damage. However, this was a less likely scenario given that no thrombi or obvious endothelial damage were seen within the left atrium, left ventricle, or aorta; and no thrombus was found at or extending from the right external carotid arteriotomy. Ligation of the external carotid artery is commonly performed with diagnostic catheterizations and has not been reported to be associated with embolic complications. Additionally, most of the blood exiting the right ventricle emptied directly into the aorta, thus physiologically causing the right ventricle to function as a left ventricle. Therefore, it is most likely that thrombi found within the right atrium and right ventricle gained access to the systemic circulation.

In people, clinical signs associated with paradoxical embolization are similar to other thromboembolic events and are related to the arterial site of embolization. Signs may arise from involvement of the cerebral (37%), peripheral (49%), coronary (9%), renal (1%), and splenic arteries (1%).¹⁰ Fatal consequences of paradoxical embolization are most commonly associated with stroke or myocardial infarction.^9,10

Treatment of paradoxical embolization and impending paradoxical embolization in people is associated with favorable survival rates and includes correction of the defect by either interventional procedures or open-heart surgery combined with thrombolytic or anticoagulant therapy.^9,13,14 Surgical corrections of such defects are often not feasible in animals because of financial constraints and lack of extensive clinical experience with such procedures. However, prophylactic anticoagulant therapy with heparin may have been beneficial in preventing thrombus formation and, thus, the clinical outcome in this cat. It is almost universal to use systemic anticoagulation therapy prior to diagnostic or interventional procedures in human cardiology; however, in veterinary cardiology, anticoagulants are not typically utilized prior to similar procedures. In people, it is generally recommended that unfractionated heparin be administered prior to the onset of catheter procedures to cause an increase in activated clotting time (ACT) to 250 to 300 seconds. Weight-adjusted dosing regimens of 50 to 100 IU/kg are typically used to achieve this ACT range.^15–17 In children, the incidence of arterial thrombosis following diagnostic catheterization procedures decreased from between 4% and 40% prior to the introduction of systemic anticoagulation with heparin in the early 1970s, to between 0.8% and 8.0% currently.^18,19 There is no analogous objective data available in animals.

While it may not seem necessary to use systemic anticoagulants in diagnostic or interventional cardiac procedures because of a lack of recognizable clinical complications in most animals, veterinarians should be aware of the possible benefits of these medications in animals that may be at risk for developing thromboembolic complications. For example, in the authors’ experience, it is not uncommon to find right-to-left shunting at the atrial level (most likely a patent foramen ovale) on two-dimensional echocardiography in dogs with valvular pulmonic stenosis. These dogs would theoretically be at risk for developing paradoxical embolization and could benefit from anticoagulant therapy during balloon valvuloplasty procedures.

Conclusion

This case report demonstrated the pathophysiology of paradoxical embolization of a right-sided thrombus in a cat. Thrombi in this cat most likely formed secondary to catheterization of a diseased right heart and reached the systemic circulation via a large VSD and dextropositioned aorta. Although the findings in this case report represented an unusual complication of cardiac catheterization, and objective data on the use of prophylactic anticoagulant therapy are lacking in animals, the application of similar anticoagulant protocols as used in humans warrants further investigation.