CLINICAL CLASSIFICATION

The Evian Classification Scheme, proposed by the World Health Organization (WHO), categorizes pulmonary hypertension based on similarities in pathophysiologic mechanism, clinical presentation, and treatment options.^13,14 This scheme has been adopted by the veterinary community.

Clinical class I: pulmonary arterial hypertension

Congenital shunts. Congenital shunts include patent ductus arteriosus, atrial septal defects, and ventricular septal defects. These defects all lead to increased pulmonary blood flow and structural changes in the vascular walls. Specifically, histopathology demonstrates hypertrophy of the small muscular pulmonary arteries and arterioles. Advanced disease is associated with fibrosis, vessel obliteration, and arteritis.¹⁶

Eisenmenger syndrome describes severe pulmonary arterial hypertension secondary to a congenital cardiac defect. In this condition, a left-to-right cardiac shunt causes severe endothelial dysfunction, which leads to increased pulmonary vascular resistance. This resistance ultimately increases right-sided heart pressures to the point of shunt reversal, and blood flows right to left through the congenital defect. Patients with Eisenmenger syndrome develop severe cyanosis, polycythemia, and congestive heart failure. In human medicine, the development of Eisenmenger syndrome secondary to an unrepaired congenital shunt is associated with a 10- to 12-fold increase in mortality; almost all patients with unrepaired patent ductus arteriosus develop Eisenmenger syndrome.¹⁷

Heartworm disease. Heartworm disease, caused by the nematode Dirofilaria immitis, is another common cause of canine class I pulmonary hypertension. Heartworm disease is diagnosed worldwide and occurs when a mosquito bite transmits D. immitis larvae to a canine host. Over a period of months, the larvae develop into adult nematodes and relocate to the right side of the heart and the pulmonary artery. Acute signs of pulmonary hypertension can be caused by an embolism of dead adult heartworms and are associated with class IV pulmonary hypertension (see below). But long-term, occlusion of large pulmonary arteries leads to pulmonary vascular proliferation, irreversible structural damage, inflammation, and vascular dysfunction that is typical of class I pulmonary hypertension.¹⁸ French heartworm, caused by Angiostrongylus vasorum, has also been associated with canine pulmonary hypertension.¹⁹

Clinical class II: pulmonary venous hypertension

Patients in the class II category develop pulmonary hypertension secondary to left-sided heart disease. Chronic left-sided heart disease leads to increased left atrial pressure, which in turn leads to increased pulmonary venous pressure. In these scenarios, pulmonary edema and hypoxia develop, and reactive pulmonary arterial hypertension occurs.³ When pulmonary venous pressure exceeds 25 mm Hg, pulmonary arterial pressure increases in an attempt to maintain pulmonary blood flow. Ultimately, pulmonary arteriole hypertrophy and pulmonary artery noncompliance develop.

Left-sided heart disease is the most common cause of pulmonary hypertension overall in both people and dogs.^13,15 While causes of left-sided heart disease may include dilated cardiomyopathy, degenerative mitral valve disease is a more common cause of canine pulmonary hypertension. In a study of 60 dogs with pulmonary hypertension, 38 dogs (63%) had pulmonary hypertension due to degenerative mitral valve disease, while only two dogs (3%) had pulmonary hypertension due to dilated cardiomyopathy.²⁰ Other studies indicate that anywhere from 14% to 31% of dogs with degenerative mitral valve disease develop pulmonary hypertension.^21,22 Although less common, class II pulmonary hypertension has been reported in people and dogs with myocarditis and atrial distention secondary to atrial fibrillation.^8,23

Clinical class III: pulmonary disease or hypoxia

Pulmonary hypertension may also occur secondary to primary pulmonary disease or chronic hypoxia. These patients are considered class III. The respiratory diseases most frequently associated with class III pulmonary hypertension in people are chronic obstructive airway disease, interstitial lung disease, and sleep-disorder breathing.⁸ In dogs, class III pulmonary hypertension has been associated with pulmonary fibrosis, pneumonia, tracheobronchial disease, and neoplasia.²² Given the breed predilection, it is not surprising to find that up to 40% of West Highland white terriers with chronic interstitial lung disease have some degree of pulmonary hypertension.²⁴

Clinical class IV: thromboembolic disease

Class IV pulmonary hypertension is caused by a thrombotic or embolic event. In people with class IV pulmonary hypertension, pulmonary artery obstruction has been associated with thromboembolism, tumors, and foreign bodies. In dogs, pulmonary thromboembolism has been associated with immune-mediated hemolytic anemia, neoplasia, protein-losing nephropathies and enteropathies, hyperadrenocorticism, sepsis, and trauma.^15,23 Given the possibility of worm emboli, heartworm disease can be included in this category as well.¹⁵

Clinical class V: miscellaneous

Class V pulmonary hypertension encompasses the miscellaneous causes of pulmonary hypertension. In people, class V includes conditions that indirectly alter cardiac blood flow (e.g. primary polycythemia vera), granulomatous diseases, and diseases that lead to the destruction of pulmonary parenchyma.¹³ In veterinary medicine, class V pulmonary hypertension is rarely reported; however, the most common conditions are likely those that cause pulmonary vasculature compression, such as neoplasia.