Percutaneous Transcatheter Closure of an Aorto-Cardiac Fistula in a Thoroughbred Stallion Using an Amplatzer Occluder Device

An 18-year-old Thoroughbred breeding stallion was referred to the Veterinary Medical Center at the University of Florida for evaluation and treatment of respiratory distress and fever. The stallion had been housed on pasture since the conclusion of the breeding season, 2 months before presentation. Two days before presentation, the stallion became lethargic and had bilateral mucopurulent nasal discharge. Examination by the referring veterinarian before referral identified pyrexia, bilateral mucoid nasal discharge, abnormal lung sounds, and a cardiac murmur. A murmur had not been noted during routine examination 8 months earlier. On physical examination, the animal was tachycardic (76 beats/min [bpm]) with a regular heart rhythm, tachypneic (40 breaths/min), and had an increased body temperature of 39.2°C. The animal weighed 500 kg with a body condition score of 3/9. Auscultation of the lungs disclosed bilateral crackles and wheezes. Auscultation of the heart identified a grade IV/VI diastolic murmur in the left fourth intercostal space, a grade III/VI holosystolic murmur in the left 5th intercostal space, and a grade III/VI continuous murmur over the right 3rd to 4th intercostal space. No jugular pulses or peripheral edema were noted. Peripheral pulses were synchronous but bounding. Hematologic abnormalities included leukocytosis (22,910/μL; reference range, 5,500–12,100/μL) with neutrophilia (21,000/μL; reference range, 2,200–8,100/μL) and a mild left shift (band neutrophils, 230/μL; reference range, 0–100/μL). Fibrinogen concentration (300 mg/dL; reference range, 100–400 mg/dL) and cardiac troponin I (<0.05 ng/mL; reference range, 0.00–0.14 ng/mL) were normal. Thoracic ultrasonography identified diffuse bilateral pleural irregularities and minimal pleural effusion. Thoracic radiographs identified a pronounced interstitial pattern with diffuse, ill-defined pulmonary nodules. The pulmonary vasculature and cardiac silhouette were partially obscured. A tracheobronchial aspirate was performed, and cytologic examination of the fluid disclosed nonseptic neutrophilic inflammation. Bacterial and fungal cultures subsequently yielded no growth. Cytologic examination of bronchoalveolar lavage (BAL) fluid indicated marked goblet cell hyperplasia and mild nonseptic mixed inflammation. Radiographic and clinical pathologic findings were suggestive of equine multinodular pulmonary fibrosis (EMPF). Recommended diagnostics included histopathologic analysis of lung biopsy specimens, and polymerase chain reaction (PCR) analysis of lung tissue and BAL cells for equine herpes virus (EHV)-2 and EHV-5. Further testing was declined by the owner because of the poor prognosis associated with severe respiratory and cardiac disease. Echocardiographya identified increased left ventricular chamber size with normal wall thickness consistent with eccentric hypertrophy (LVIDd, 16.71 cm, normal, 11.9 ± 0.7 cm; LVIDs, 8.7 cm; normal, 7.4 ± 0.7 cm; LADd, 19.1 cm, normal, 12.82 ± 0.78 cm1). Fractional shortening was increased (48%; reference range, 32–45%). The aortic and mitral valves both were severely thickened and there was prolapse of the right coronary cusp of the aortic valve. There was an 8 mm fistula between the right coronary sinus and the right ventricle just below the tricuspid valve consistent with an aorto-cardiac fistula. Color flow Doppler echocardiography indicated continuous turbulent blood flow across the aorto-cardiac fistula (Fig 1). Severe aortic insufficiency and mitral regurgitation were detected. Electrocardiography identified sinus tachycardia. Based on the echocardiographic findings, diagnoses of rupture of the right coronary sinus resulting in aorto-cardiac fistula, as well as severe aortic insufficiency and mitral regurgitation resulting from myxomatous valvular degeneration were made. Echocardiographic images of the left ventricular outflow tract obtained from the right parasternal window. Color flow Doppler indicates turbulent blood flow in the aorto-cardiac fistula (arrow). RV, right ventricle; RA, right atrium; LV, left ventricle; AO, aorta; PA, pulmonary artery; LA, left atrium. Antimicrobial therapy (potassium penicillin G, 20,000 U/kg IV q6h and gentamicin, 6.6 mg/kg IV q24h) for treatment of possible bacterial pneumonia was initiated at admission and continued for 5 days. Empirical therapy for EMPF with dexamethasoneb at 0.075 mg/kg IV q24h was initiated on day 2 of hospitalization after airway cytology and preliminary culture results indicated that bacterial or fungal pneumonia was unlikely. Treatment with valacyclovir was discussed with the owner but declined because of the high cost combined with the lack of scientific evidence of efficacy in the treatment of EMPF. By day 5 after admission, the horse had a normal temperature and respiratory rate, and the lung sounds were markedly improved. Therapy with furosemidec (1 mg/kg IV q12h) and quinaprild (0.25 mg/kg PO q24h) was initiated in an attempt to decrease preload and afterload. Because of the poor to guarded prognosis associated with aorto-cardiac fistula in horses and the risk of sudden death associated with breeding, the decision was made to attempt transcatheter repair of the aorto-cardiac fistula with an Amplatzer septal occluder (ASO).e The owner was made aware that even if the procedure was successful, occlusion of the aorto-cardiac fistula would not improve the severe aortic insufficiency and mitral regurgitation. Hence, the long-term prognosis was poor. Transcatheter closure of the aorto-cardiac fistula was performed standing under sedation. The horse was sedated (detomidine,f 0.01 mg/kg IV and butorphanol,g 0.1 mg/kg IV) and the right jugular grove was prepared aseptically. Preoperative antimicrobials (potassium penicillin G, 20,000 U/kg IV and gentamicin, 6.6 mg/kg IV) were administered. A right carotid cut-down approach was performed as previously described2 at the junction of the distal and middle third of the neck, an estimated 70 cm from the heart to ensure the 80-cm delivery sheath was of adequate length. The carotid artery was isolated with 2 Penrose drains. A 10 Fr introducer was placed in the right carotid artery. A 5 Fr multipurpose angiographic catheter was placed within a 7 Fr 45°-angled ASO delivery sheath. Using echocardiographic imaging guidance, this coaxial system was introduced into the aortic root and was used to successfully cross the fistula into the right ventricle. The 7 Fr delivery sheath was advanced into the right ventricle and the angiographic catheter was removed. A 10 mm ASO was loaded onto a delivery cable and advanced through the delivery sheath. The distal disk was deployed in the right ventricle. Then, the sheath and ASO were simultaneously withdrawn until the disk was in contact with the right ventricular side of the interventricular septum. The proximal disk then was deployed and secured (Fig 2). The device was examined by echocardiography and did not appear to interfere with the aortic and tricuspid valves and did not obstruct flow through the right coronary artery. Color-flow Doppler echocardiography showed trivial flow across the device and the device was deployed. The delivery sheath and delivery cable were removed from the introducer. The introducer was removed, the carotid artery was repaired, and the incision was closed. Long axis (A) and short axis (B) echocardiographic images of the left ventricular outflow tract obtained from the right parasternal window. The distal and proximal disks of the Amplatzer septal occluder (ASO) are indicated (black arrows). The ASO is attached to the delivery cable (open arrow). RV, right ventricle; RA, right atrium; AO, aorta. Echocardiography 24 hours after the procedure indicated that the device was still in place with no flow across it. Cardiac auscultation indicated resolution of the grade III/VI continuous murmur over the right 4th intercostal space. Measurements of the cardiac chambers were not changed from the previous examination. The horse was discharged 1 day after the procedure on day 8 of hospitalization. Stall confinement was recommended and treatment with quinipril and furosemide was continued. A tapering course of dexamethasone (0.075 mg/kg IV q24h for 7 days, 0.08 mg/kg IM q24h for 7 days, 0.06 mg/kg IM q24h for 7 days) was continued for treatment of presumptive EMPF. The horse did well clinically at home, remaining afebrile and maintaining a good appetite, although the tachycardia persisted with a resting heart rate of 56–64 bpm. The horse presented for re-examination 18 days later. Physical examination disclosed a normal respiratory rate and normal bronchovesicular lung sounds during auscultation with a rebreathing bag. The horse's body condition score had decreased to 2/9 and the horses had lost 44 kg. Cardiac auscultation was unchanged from discharge. Echocardiographic examination confirmed that the ASO was still in place with no detectable flow across it. The left atrium remained enlarged and was unchanged compared with previous examination. The left ventricle had increased in size (LVIDd 17.44 cm compared with 16.71 cm at previous examination; LVIDs 10.17 cm compared with 8.7 cm at previous examination). The regurgitant jets across the mitral and aortic valves appeared more pronounced subjectively. Because of the progressive volume overload, hydralazine therapy (0.25 mg/kg PO q12h) was initiated in an attempt to decrease afterload. Thoracic radiographs were markedly improved with only a mild diffuse interstitial pattern remaining and no distinct nodules. Hematologic examination identified ongoing but improved leukocytosis (13,740/μL) with mature neutrophilia (10,820/μL) and normal fibrinogen concentration (400 mg/dL). Because of the improvement in clinical signs related to the respiratory tract, improved leukocytosis, and almost complete radiographic resolution of the nodular interstitial pattern, therapy with dexamethasone was discontinued. The horse presented for re-examination 18 days later, 45 days after initial presentation. One week before re-examination, the horse had become lethargic, anorexic, and had developed ventral and limb edema. The horse's body condition had decreased. Echocardiographic examination was minimally changed from the previous examination. Auscultation and ultrasonography of the lungs remained normal. Based on its clinical decline and progressive heart failure that was unresponsive to medical treatment, the horse was euthanized. At postmortem examination, the total cardiac weight was increased at 1.7% of body weight (reference range, ≤ 0.7% of body weight). Moderate, diffuse thickening of the mitral and aortic valves consistent with chronic endocardiosis was noted. The right coronary cusp of the aortic valve was thickened by redundant fibrous connective tissue. An aorto-cardiac fistula was confirmed from the right coronary sinus to right ventricle and the ASO was properly positioned across the defect. There was no endothelialization over the ASO in the region of the right coronary sinus but there was mild endothelialization present over the right ventricular side of the ASO (Fig 3). Histopathology of the heart disclosed mild to moderate myocardial fibrosis within the left ventricle and interventricular septum. Histopathology of the lungs identified moderate pulmonary interstitial fibrosis with lymphohistiocytic alveolitis and bronchiolitis. Polymerase chain reaction analysis of lung tissue for EHV-2 and EHV-5 was negative. Postmortem image of the Amplatzer septal occluder (ASO) as seen from the right ventricular side. The tricuspid valve is indicated (open arrow). There is mild endothelialization present at the center of the ASO (solid arrow). RV, right ventricle; RA, right atrium. To the authors' knowledge, this is the 1st report of occlusion of an aorto-cardiac fistula in a horse. Aorto-cardiac fistula is an uncommon condition that typically occurs in aged breeding stallions, but there are rare reports in geldings and mares.3–6 Fistulas sometimes occur because of rupture of an aneurysm of the right coronary sinus (sinus of Valsalva) or they may occur without preexisting dilatation as in the case presented here. Most frequently, the fistula forms between the right coronary sinus and right ventricle, as in the horse in this report, although the aneurysm also may rupture into the right atrium or dissect into the ventricular septal myocardium.6 Intact aneurysms of the right coronary sinus have been identified during echocardiography in horses.3,7 Acute onset of clinical signs after rupture of the aneurysm is common, with signs of colic associated with thoracic pain, distress, congestive heart failure, and sudden death. In breeding stallions, signs may occur during or immediately after breeding.5,8 Although the horse of this report was a breeding stallion, the onset of clinical signs was not associated with breeding or any other stressful event. It is unknown how long the horse had the aorto-cardiac fistula before presentation. Aorto-cardiac fistula results in continuous left-to-right shunting of blood and subsequent volume overload of the left ventricle. A continuous murmur loudest on the right side is most frequently reported.6 In the horse of this report, the continuous murmur on the right side attributed to the aorto-cardiac fistula was completely obliterated after occlusion of the fistula. Concurrent aorto-cardiac fistula and chronic degenerative disease of the mitral and aortic valves have been reported previously in 2 horses.3,6 Pre-existing aortic and mitral insufficiency likely contributed to left-sided volume overload and subsequent heart failure in this horse. Aortic insufficiency can occur after rupture of an aortic root aneurysm because of loss of support of the aortic root or may be a pre-existing condition associated with valvular degeneration, as was suspected in this case. Although aortic insufficiency is common in aged horses, it does not typically result in formation of an aortic aneurysm.9 However, chronic aortic regurgitation may predispose to aortic dilatation, resulting in formation of an aneurysm.3,6 The concurrent pulmonary disease in this horse likely was unrelated to the aorto-cardiac fistula. Acute onset left-sided heart failure might have resulted in pulmonary edema. The interstitial pattern evident on thoracic radiographs might have been the result of pulmonary edema or interstitial disease. However, the diffuse pulmonary nodules were not consistent with pulmonary edema alone. A specific cause of the pulmonary fibrosis was not apparent histologically because of the chronicity of the lesion. Possible causes of this lesion are numerous and include viral infection, irritants, toxins, or a chronic inflammatory reaction to an environmental antigen.10 The clinical signs, clinicopathologic abnormalities, radiographic findings, response to treatment with corticosteroids, and histopathologic findings all were consistent with EMPF, a fibrotic lung disease associated with EHV-5.11,12 Although the lung tissue was negative for EHV-2 and EHV-5 by PCR assay, testing was performed after 1 month of treatment with corticosteroids and after resolution of clinical signs. The role of EHV-5 and EHV-2 in the etiology of EMPF remains unclear. In humans, aortic sinus aneurysms may be congenital or acquired.13 Congenital defects are more common, and reported more frequently in males than females.14 Congenital aneurysms dilate progressively to the point of rupture, typically in the 3rd or 4th decade of life.13 Acquired aneurysms are less common, occurring secondary to conditions affecting the aortic wall, such as infection, degenerative disease, or thoracic trauma. Surgical repair of ruptured aneurysms is recommended in people because the prognosis without repair is poor.15 Although mortality is low, morbidity associated with cardiopulmonary bypass and thoracotomy is a concern.16,17 Transcatheter closure of ruptured aortic sinus aneurysms has been performed in people with congenital aneurysms.18–22 Although it has been reported in a relatively small number of patients, it appears to be safe and effective. Complete occlusion of the defect is important because residual shunting has been associated with hemolysis because of high pressure flow.23 There currently are no devices specifically designed for correction of this defect.24 Survival time for horses with aorto-cardiac fistulas has been reported to range from a few days to years.3–6,17 Because of the risk of sudden death, use as a performance horse or breeding stallion is not recommended, although 1 stallion was successfully bred for 1 year after identification of the fistula.8 Treatment of horses with aorto-cardiac fistulas has focused on anti-arrhythmic therapy of ventricular tachycardia.3,6 With the exception of short-term treatment with furosemide in 2 horses,6 and furosemide and digoxin in 1 horse,4 treatment of congestive heart failure in horses with aorto-cardiac fistula has not been reported. The horse of this report was treated with quinapril (an angiotensin converting enzyme inhibitor), furosemide, and, later, hydralazine (a vasodilator). Because of the valvular endocardiosis and associated severe regurgitation and cardiac enlargement, the long-term prognosis for this horse was poor and closure of the fistula was not expected to alleviate the signs of heart disease. The aorto-cardiac fistula may have aggravated an already failing left heart. Alternatively, occlusion of the aorto-cardiac fistula may have intensified the aortic insufficiency and possibly contributed to the progression of heart failure. Nevertheless, successful correction of the defect indicates that in the future, aorto-cardiac fistulas detected before development of severe cardiomegaly may be treated successfully, allowing return to breeding. This report indicates that transcatheter occlusion of aorto-cardiac fistulas with an ASO is possible and deserves further investigation. Additional studies will be needed to determine whether horses can safely return to low-level performance after occlusion of an aorto-cardiac fistula. aVivid 3, General Electric Healthcare, Waukesha, WI bDexamethasone, Phoenix Pharmaceuticals, St. Joseph, MO cSalix, Intervet, Millsboro, DE dQuinapril, Apotex Corporation, Weston, FL eAmplatz septal occluder. AGA Medial Corporation, Plymouth, MN fDormosedan, Pfizer Animal Health, New York, NY gTorbugesic, Fort Dodge Animal Health, Fort Dodge, IA The authors thank Dr Carlos Perez of Ferguson & Hammock Equine Hospital for the referral of this case.