An 11-year-old, female spayed mixed breed dog was referred to cardiology for two episodes of syncope. Her owners reported an occasional cough and a slowly decreasing activity level and appetite over a two-week period. She was previously healthy. Prior to presentation, the patient collapsed on a walk but quickly recovered. She presented to her referring veterinarian the following day and collapsed in the lobby. In this episode, she remained weak with an increased respiratory rate and effort. She had a systolic blood pressure of 90 mmHg. Thoracic radiographs showed an enlarged cardiac silhouette and a patchy interstitial pulmonary pattern. CBC was normal with the exception of a mildly elevated hematocrit and mild neutrophila. The referring veterinarian sent her straight to the cardiology department for further evaluation.
On presentation, the patient was weak and could only walk a few steps without stopping to rest. Her respiratory rate was mildly elevated with significantly increased respiratory effort. The hypotension persisted and there was a sinus rhythm with a heart rate of 150 beats per minute. She had fine inspiratory pulmonary crackles bilaterally with no heart murmur. She was placed in an oxygen cage while the team prepared for diagnostic testing.
Due to the enlargement of the cardiac silhouette, syncope and hypotension, an echocardiogram was the next step. The diagnosis: severe pulmonary hypertension.
Image 1. The patient’s thoracic radiographs showed an enlarged cardiac silhouette and a patchy interstitial pulmonary pattern.
Image 2. Additional view of the patient’s thoracic radiography.
Pathophysiology of pulmonary hypertension (PH)
The pulmonary circulation is normally a low pressure and low resistance system. The normal systolic pressure in the pulmonary arterial tree is 15 to 30 mmHg, which is significantly lower than that of the systemic arteries. Pulmonary hypertension is defined as a systolic pulmonary arterial pressure greater than 35 mmHg. In this setting, there is an imbalance of vasoconstricting and vasodilating pathways of the pulmonary arterial walls resulting in hypertrophy and further vasoconstriction, fibrosis and thrombosis. By this mechanism, pulmonary hypertension can be progressive and irreversible.
The high pressure in the pulmonary arterial tree increases afterload to the right ventricle, which results in a decrease in cardiac output. This explains the most common clinical signs of syncope and exercise intolerance. Furthermore, the resultant neurohormonal activation leads to heart failure in some patients.
Causes of pulmonary hypertension
In dogs, we most commonly see pulmonary hypertension secondary to chronic pulmonary disease, heartworm infection or mitral valve disease. Other causes, such as congenital shunts and pulmonary thromboembolism, should also be considered.
Causes of PH
Obstruction of the lumen of the pulmonary arteries
Thrombus or embolus
Systemic inflammatory state (neoplasia, IMHA)
Large congenital shunts
Atrial septal defect
Ventricular septal defect
Patent ductus arteriosus
Pulmonary pathology and hypoxia
Chronic obstructive pulmonary disease
Interstitial pulmonary fibrosis
High altitude sickness
Pulmonary venous hypertension
Mitral valve disease
Pulmonary venous stenosis
Patients with severe pulmonary hypertension present with symptoms related to low cardiac output or heart failure, such as exercise intolerance, syncope, shortness of breath, and abdominal distension. Pulmonary edema can result in acute dyspnea. Symptoms can also be related to the initiating cause of pulmonary hypertension, such as chronic cough.
Physical examination findings are variable and usually related to the underlying cause of pulmonary hypertension. Weak femoral pulses, ascites, peripheral edema or jugular pulses may be present. Respiratory symptoms, such as tachypnea, cyanosis, and pulmonary crackles or heart murmurs, may be present, depending on the initiating factors.
The clinical pathology testing indicated depends on the potential underlying cause. Complete blood count, serum chemistry, urinalysis and heartworm testing are indicated. Pulmonary hypertension increases circulating NT-proBNP. Thoracic radiography is indicated to help determine the inciting cause of pulmonary hypertension, such as chronic pulmonary parenchymal disease. Some patients have radiographic findings supportive of pulmonary hypertension, including right-sided enlargement of the cardiac silhouette, dilation of the main pulmonary artery, tortuosity and blunting of the pulmonary arteries, or dilation of the caudal vena cava. Non-cardiogenic pulmonary edema occurs in some cases of severe pulmonary hypertension. CT scan can be used to evaluate the pulmonary vasculature.
Echocardiography is the most common method of diagnosis. It can be used to estimate pulmonary artery pressure. Valvular regurgitation velocity is measured with Doppler to classify pulmonary hypertension as mild, moderate or severe. The degree of secondary remodeling in the form of right ventricular hypertrophy and main pulmonary arterial dilation can also be assessed, and congenital shunts are diagnosed.
The gold-standard method is direct pressure measurement with a pulmonary arterial catheter. While this is a straightforward procedure, it is rarely needed in the clinical setting.
Image 3 and 4. The patient’s echocardiogram shows right ventricular enlargement and high velocity tricuspid valve regurgitation.
Pulmonary hypertension patients can have significant improvement in quality of life with appropriate therapy. The long-term prognosis depends on the underlying cause. Goals of therapy are to dilate the pulmonary arteries to improve oxygenation and perfusion, which often resolves symptoms such as syncope and exercise intolerance.
Supplemental oxygen – In the acute setting, supplemental oxygen can be a powerful pulmonary arterial dilator and can improve perfusion, oxygenation and patient comfort very quickly.
Sildenafil – Sildenafil (and other phosphodiesterase 5 inhibitors) are effective and commonly used as pulmonary vasodilators.
Pimobendan – Pimobendan is a phosphodiesterase 3 inhibitor and is used frequently in the author’s practice to improve cardiac output and anecdotally improves symptoms. This is also indicated in cases of pulmonary venous hypertension secondary to left heart disease.
Treatment of underlying cause – Bronchodilators, anti-thrombotics, anti-inflammatory drugs, heartworm therapy, etc., are used as indicated to address the underlying cause.
Heart failure therapy – Abdominocentesis and diuretic therapy are indicated if congestion is present.
Back to our patient …
The patient was admitted to the hospital to initiate therapy and supportive care. She was placed in an oxygen cage at 40%. Intravenous fluids were administered at a low-maintenance rate. Pimobendan was prescribed. Her respiratory rate and effort were much improved in the oxygen cage and her systolic blood pressure increased to 115 mmHg. Sildenafil therapy was initiated. No heartworm antigen was detected on an in-house blood test. Further diagnostics to confirm the underlying pathology were declined by the owner due to finances and the risk associated with general anesthesia, so empiric therapy for chronic pulmonary disease was initiated, consisting of inhaled fluticasone and albuterol.
Image 5. Additional view of patient’s echocardiogram.
For 48 hours, the patient continued to be comfortable with oxygen supplementation but became quickly dyspneic on room air. By the third day, she was able to tolerate short walks outside off of oxygen support. After five days in the hospital, her lung sounds, oxygen saturation and blood pressure had improved, though she remained short of breath with activity. She was discharged on oral sildenafil and pimobendan as well as inhaled albuterol and fluticasone. Her owners were instructed to exercise restrict for the week until her recheck exam. At this visit, her owners reported good quality of life and almost normal behaviors, with some shortness of breath with moderate activity. Her blood pressure was normal and no other diagnostics were performed at this visit. Her medications were continued as prescribed at discharge. Months later, she continues to do well at home, though we did prescribe an at-home oxygen tank and mask to help her quickly when she had the occasional episode of increased respiratory effort.
Pulmonary hypertension can cause a variety of symptoms, and some of these patients are very unstable on arrival. While this is generally a progressive disease, cases like this one are rewarding to treat because of the rapid and dramatic improvement in clinical signs.
Bach JF, Rozanski EA, et al. Retrospective evaluation of sildenafil citrate as a therapy for pulmonary hypertension in dogs. J Vet Intern Med 2006;20:1132-1135.
Kellihan HB, Waller KR, et al. Acute resolution of pulmonary alveolar infiltrates in 10 dogs with pulmonary hypertension treated with sildenafil citrate: 2005-2014. J Vet Cardiol 2015 Sep;17(3):182-91.
Kellihan HB, Stepien RL. Pulmonary hypertension in dogs: diagnosis and therapy. Vet Clin NA 2010:40(4):623-641.