A 9-month-old spayed female Labradoodle was evaluated for collapse.
She had been having increasingly frequent collapsing episodes since she was 5 months old, and recently the episodes had been occurring approximately three times a day. The episodes occur after exertion, and the owners noticed that she becomes progressively weaker and tucks her tail between her legs before falling to the ground. Her respiratory rate increases during these events. Occasionally she drags her back legs, and she remains alert with no urination or defecation. After sitting in sternal recumbency for 1 to 2 minutes, she resumes normal activity and does not show signs of lameness or discomfort. Physical examination was unremarkable other than a loud second heart sound. A brief neurologic examination was normal.
A brief focused ultrasound was performed. No effusions were noted, the left atrium was subjectively normal, and the right ventricle appeared enlarged.
Her PCV and total solids were 70% and 6.8 g/dL, respectively.
What are some differentials for collapse, and how do the results of this initial testing help narrow the differential list?
A common first step when evaluating an animal for collapse is to differentiate between syncope, seizure, and other causes such as neuromuscular disease or generalized weakness. In the present case, classic features of seizures are not described (such as pre- or post-ictal periods, chomping, rhythmic muscle movements, and urination/defecation). The brevity of the events and the association with exertion are both findings that could be consistent with syncope, but the facts that the hind limbs appear to be more dramatically affected and she does not lose consciousness are less consistent with syncope. Orthopedic causes and generalized weakness both seem unlikely given that she is normal between events, but neuromuscular causes such as exercise-induced collapse (EIC) could still be possible.
A broader approach to differentials for collapse would be to determine whether the underlying cause of the episodes is cardiac, neurologic, or other (metabolic, musculoskeletal, etc.). Initial testing to help determine which body system may be the root cause could include ultrasound, thoracic radiographs, ECG, and point-of-care blood work.
In the present case, the finding of right heart enlargement on focused ultrasound increases concern for a cardiac-related cause of the event, such as structural heart disease (congenital or acquired), pulmonary hypertension, or intermittent arrhythmia.
The pronounced polycythemia in this dog provides another diagnostic clue. Polycythemia can be categorized in a several ways to help determine the underlying cause. The first distinction is whether polycythemia is absolute or relative: absolute polycythemia is a true increase in red blood cells, while relative describes a normal amount of red blood cells with a reduced amount of serum (dehydration). Absolute polycythemia can be then be described as primary (resulting from abnormal bone marrow production of red blood cells, otherwise known as polycythemia vera), or it can be secondary to excess production of erythropoietin, either as an appropriate physiologic response to chronic hypoxemia or from inappropriate production resulting from a variety of neoplastic processes.
In this case, neither physical examination nor total solids suggest dehydration, so the polycythemia is thought to be absolute. The next step is to determine the underlying cause (e.g. polycythemia vera, hypoxemia, neoplasia). Given the her age, hypoxemia resulting from right-to-left shunting across a congenital heart defect (such as a ventricular septal defect, an atrial septal defect, or a patent ductus arteriosus) would be a leading differential, especially in light of the preliminary testing suggestive of right heart enlargement.
Therefore, an echocardiogram was performed, and right ventricular eccentric and concentric hypertrophy (dilated chamber with thickened walls) was confirmed. The tricuspid regurgitation velocity was markedly elevated, and the pulmonic valve was normal, suggesting that the dog had severe pulmonary hypertension. No ventricular or atrial septal defect was visible, but a patent ductus arteriosus (PDA) was present, and the flow across the PDA was right-to-left (“reverse” PDA).
A right-to-left shunting PDA can explain both the clinical events and the diagnostic findings of right heart enlargement and polycythemia in this dog. Because the PDA connects the aorta and pulmonary artery after the aortic arch has bifurcated blood supply to the front end of the body, if there is right-to-left shunting, then the deoxygenated blood flows from pulmonary artery into the aorta and then to the caudal half the body. The resulting tissue hypoxia in the caudal part of the body can cause hind end weakness and collapse episodes, especially with exertion. Additionally, the kidneys detect hypoxemia and increase erythropoietin production (appropriate physiologic response), resulting in polycythemia.
In order for blood to flow from the pulmonary artery into the aorta (right-to-left) across a PDA, there must be severe pulmonary hypertension, such that the pulmonary artery pressure is higher than the pressure in the aorta. Pulmonary hypertension can develop from the chronic pulmonary over-circulation that occurs with a left-to-right PDA, or the high pulmonary pressures that are normal in the fetus can persist at birth (persistent fetal pulmonary hypertension). The presence of pulmonary hypertension increases the workload of the right ventricle, and therefore right ventricular enlargement is an expected compensatory response.
There are several important differences in clinical presentation and management of right-to-left shunting PDAs compared to typical (left-to-right shunting) PDAs. While dogs with left-to-right shunting PDAs generally have classic physical examination findings (loud, continuous murmur, bounding arterial pulse quality), physical examination in dogs with reverse PDAs may be more subtle, and they may have no murmur at all. Since deoxygenated blood only flows to the back end of the body, a classic physical examination finding for a reverse PDA is “differential cyanosis,” where the nail beds and mucosa are pink in the front-end but cyanotic in the hind-end. However, this can be difficult to detect in dogs with pigmented mucous membranes.
Unfortunately, surgical repair of right-to-left PDA is contraindicated due to the severe fixed pulmonary hypertension. While dogs with successfully occluded left-to-right PDAs typically live a normal life, dogs with right-to-left PDAs are reliant on palliation with medical management (e.g. intermittent phlebotomy and medications such as sildenafil, pimobendan, or hydroxyurea). However, medical management can still potentially result in good quality of life for years!
Dr. Emily Tompkins Karlin is an assistant professor and alumna of Cummings School of Veterinary Medicine at Tufts University. She is board-certified by the American College of Veterinary Internal Medicine, Cardiology (ACVIM).