History
An 18-year-old 510-kg (1,122-lb) Paint mare was referred to the cardiology service at the Veterinary Teaching Hospital of the University of Padua. The mare had a 3-month history of signs of depression, exercise intolerance, anorexia, tachycardia, fever, tachypnea, and weight loss. In addition, a heart murmur had been recently detected.
Clinical Findings
Upon evaluation, the mare was in poor body condition (body condition score, 3/9) and had ventral edema, pale mucous membranes, and capillary refill time of 2 seconds. The horse was tachycardic (heart rate, 75 beats/min) with a respiratory rate of 40 breaths/min. Cardiac auscultation revealed a 5/6 continuous heart murmur that was best heard over the left and right hemithorax but was louder over the right heart base. A 4/6 holosystolic murmur over the left apex region was also auscultated.
Echocardiographic and echo-Doppler examinations revealed moderate to severe right atrial and mild to moderate right ventricular enlargement. An aneurysm of the right sinus of Valsalva protruded into the right atrium. With color flow Doppler ultrasonography, an aorto-cardiac fistula (ACF) was suspected. Additional echocardiographic findings included mildly thickened mitral valve leaflets producing mitral regurgitation, left atrial enlargement, left ventricular dilation, and mild pericardial effusion. Owing to the poor prognosis for the horse, the owner elected euthanasia (by IV administration of a solution of concentrated potassium chloride after the horse was anesthetized).
Gross Findings
Gross postmortem examination of the heart and great vessels revealed a small amount of serosanguineous fluid in the pericardial sac and severe dilation of the pulmonary artery and right atrium. In transverse section, the right ventricle had severe eccentric hypertrophy. A 1-cm-diameter area of a ruptured, dome-shaped swelling was noted within the right atrium, close to the origin of the septal leaflet of the tricuspid valve (Figure 1). A fistula connected this area to a focal, thickened, irregular region in the right sinus of Valsalva, located just dorsal to the aortic valve. Subcutaneous and pulmonary edema and dilated venous vessels were additional findings.
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Histopathologic Findings
A longitudinal section of tissue close to the ruptured area (including the proximal portion of the ascending aorta, the interatrial septum, and the right sinus of Valsalva) was examined microscopically. There was a large aneurysm of the aortic wall, dorsal to the right sinus of Valsalva and below the opening of the right coronary artery, that led into the right atrium dorsally to the septal leaflet of the tricuspid valve (Figure 2). Microscopic examination of sections of multiple portions of the ascending aorta revealed fragmentation and thinning of the elastic fibers separated by periodic acid–Schiff-positive interstitial homogeneous material. These findings were consistent with mucoid extracellular matrix accumulation (MEMA).1 Moderate myxomatous degeneration of the distal portion of the mitral valve leaflets was also found.
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: aortic MEMA in a horse with a ruptured aneurysm of the right sinus of Valsalva associated with an ACF.
Comments
Clinically relevant diseases of equine arteries include aortitis, arteritis, thrombosis of the aortic-iliac or other arteries,2,3 arteriovenous fistulas,4,5 and arterial aneurysms or rupture, such as aortic sinus aneurysm (ASA) and aortic root rupture.6,7 Rupture of an aortic sinus of Valsalva aneurysm and an associated ACF are considered rare both in humans and horses. The right coronary sinus is most commonly affected in both species.6,8–12 In horses, rupture of the aortic root or right ASA can lead to an ACF, permitting communication between the aorta and the right ventricle or, less frequently, the right atrium or ventricular septum, whereas rupture of the aortic arch can lead to an aorto-pulmonary fistula.6–11,13,14 Among horses, stallions are more commonly affected by ACFs, compared with geldings and mares; there is no clear breed predisposition,6,7,9–11,13–16 although Friesians are more commonly affected by aorto-pulmonary fistulae.11 In humans, ASAs and associated ACFs can be congenital and develop because of weakness at the junction of the aortic media and the annulus fibrosis caused by lack of elastic or muscular tissue in the aortic wall. Aortic sinus aneurysms in humans can also be acquired as a consequence of inflammation, trauma, or degenerative disease.12
Two main types of pathological lesion in horses with an ACF have been described: a fistula that dissects through the aortic ring to the right ventricle, right atrium, or into the ventricular septum; or an ASA that ruptures into the right atrium or ventricle or that creates tracts dissecting through the ventricular septum.6,10 The reported histopathologic findings include abnormally oriented connective tissue in proximity to the fistula (with uneven distribution of the extracellular matrix and fibrocytes) or the thinning of the collagen layer16; in cases of subendocardial dissection and aorto-ventricular fistula, mature and immature fibrous tissues line the lesion and disrupt the conduction tissue.10 In another horse, the ACF was associated with endocarditis.14 The histologic features of the aorta of the horse of the present report were similar to those described for human patients with MEMA, which have been frequently associated with ascending aorta aneurysm formation.8,12 Mucoid extracellular matrix accumulation is characterized by an accumulation of basophilic ground substance with formation of extracellular pools in the tunica media probably caused by primary protein disorders.1,17,18 These changes have been referred to by some authors as cystic medial necrosis,17,18 but the nomenclature of the degenerative aortic histopathologic lesions in humans have recently been revised and MEMA is now considered a more technically accurate term.1
The disruption of collagen, elastin, and smooth muscle results in weakening of the arterial wall and aortic dissection or aneurysm development.17,18 In humans, MEMA is frequently associated with a primary disorder of collagen (ie, Marfan syndrome) and fragility of the aortic tunica media is considered attributable to fibrillin-1 deficiency.17 Therefore, MEMA is usually observed in young patients but can also be found in geriatric individuals without Marfan syndrome.1,17,19 Some controversy exists regarding the histologic diagnosis of MEMA, because the histologic changes can develop in a normal aging aorta, but it is generally accepted that severe degeneration of the tunica media underlies aortic wall lesions.17,19 Mucoid extracellular matrix accumulation is sometimes associated with other congenital heart defects in humans,17 including ventricular septal defect, bicuspid aortic valve, aortic valve insufficiency, pulmonary valve stenosis, coarctation of the aorta, atrial septal defect, and subvalvular aneurysms.1,12,17 No congenital cardiac abnormalities were found in the horse of the present report, although myxomatous mitral valve degeneration was an additional finding. Aorto-cardiac fistula should be included as a differential diagnosis for a heart murmur in an elderly horse. Degenerative conditions, such as MEMA, can be responsible for equine ASA and rupture, similar to findings in humans.
Acknowledgments
The authors thank Dr. Matteo Gianesella and Michele Povinelli of the University of Padua for technical assistance.
References
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