Non-Invasive Diagnosis of Pulmonary Hypertension in Dogs

Pulmonary hypertension (PH) in canines is defined as pulmonary arterial systolic pressure greater than 30 mmHg, pulmonary arterial diastolic pressure greater than 15 mmHg, or mean pulmonary arterial pressure greater than 20 mmHg. Pulmonary arterial pressure is dependent on right ventricular cardiac output, pulmonary vascular resistance, and pulmonary venous pressure. PH is seen in dogs with myxomatous mitral valve disease (MMVD), thromboembolic disease, heartworm disease, congenital cardiac shunts, and various respiratory diseases. Clinical symptoms include syncope, exercise intolerance, and progressive cardiopulmonary decline. The prognosis for PH is poor, although improvement has been noted with use of the drug sildenafil, a pulmonary vasodilator.

Non-invasive diagnosis of PH is made by estimating pulmonary arterial pressure from doppler echocardiographic estimates of the maximum velocity of tricuspid or pulmonary artery regurgitant jets (blood flowing through the valve in the wrong direction). However, not all dogs with PH exhibit such regurgitant jets. With funding from CHF Grant 01982: Personalized Medicine: The Intersection of Genotype and Drug Responsiveness in the Treatment of Canine Pulmonary Hypertension, researchers at the University of California, Davis assessed genotype and response to sildenafil in dogs with PH. As part of their research they examined the diagnostic value of quantitative indirect echocardiographic indices of PH to predict pulmonary artery pressure in dogs with varying degrees of PH. (Diagnostic Value of Right Pulmonary Artery Distensibility Index in Dogs with Pulmonary Hypertension: Comparison with Doppler Echocardiographic Estimates of Pulmonary Arterial Pressure. J Vet Intern Med 2016;30:543–552.)

Several quantitative indirect echocardiographic indices have been evaluated for diagnosis of PH in canines, but they lack adequate sensitivity and specificity. Based on promising results using the right pulmonary artery distention (RPAD) index to diagnose PH in dogs with heartworm disease, researchers evaluated this index in a population of 69 client-owned dogs with chronic PH secondary to a variety of diseases. Results confirmed that RPAD accurately predicted PH in dogs with mild disease (peak tricuspid regurgitation pressure gradient greater than 36 mmHg) and may be more accurate than other indices in dogs with moderate to severe disease (peak tricuspid regurgitation pressure gradient greater than 50 mmHg).

The RPAD index essentially measures the right pulmonary artery shortening fraction. The examiner measures the minimum diastolic and maximum systolic internal diameter of the right pulmonary artery in the long axis plane using two-dimensional echocardiography. The RPAD index is the percent change in right pulmonary artery diameter throughout one cardiac cycle. Since these measurements are routinely acquired by veterinary echocardiographers, the RPAD index may be a valuable tool to screen for PH, especially in patients with inconsistent or no tricuspid valve regurgitation. Collaborating with their donors and funded-researchers, CHF will continue to find and fund valuable studies like this one to find more accurate diagnostics and better treatments for diseases such as canine pulmonary hypertension. Learn more at akcchf.org.

UPDATE:

Researchers demonstrated the effectiveness of treating pulmonary hypertension in dogs with the medication sildenafil. However, dogs with a previously identified genetic mutation affecting the enzyme upon which sildenafil acts, showed a lesser response to this medication when measured via improvement in quality of life. Measuring a dog’s cGMP levels and determining if they have the gene mutation may predict how well they respond to sildenafil. These findings may inform individualized treatment recommendations for dogs with pulmonary hypertension.

Read the latest publication resulting from CHF Grant 01982 at:
Ueda, Y., Johnson, L. R., Ontiveros, E. S., Visser, L. C., Gunther-Harrington, C. T., & Stern, J. A. (2019). Effect of a phosphodiesterase-5A (PDE5A) gene polymorphism on response to sildenafil therapy in canine pulmonary hypertension. Scientific Reports, 9(1), 6899.
https://doi.org/10.1038/s41598-019-43318-z