Matthew W. Miller, DVM, MS, DACVIM (Cardiology)
College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA
Dogs diagnosed with pulmonary hypertension are most commonly small breed and middle aged to older, which is probably reflective of the high prevalence of pulmonary hypertension in patients with chronic, degenerative, mitral valve disease. The most common presenting complaints include exercise intolerance, as well as cough, dyspnea, and syncope. Physical examination findings may include a heart murmur, typically of tricuspid regurgitation, as well as a very prominent or split second heart sound (S2). Increased adventitia with lung sounds, ascites, and cyanosis may also be present.
Routine diagnostic hematologic and biochemical diagnostics should be performed. These diagnostic tests should be reviewed with an emphasis on systemic diseases that may predispose dogs to pulmonary thromboembolism. Despite the perceived risk of heartworm infection, a heartworm antigen test should always be obtained. Thoracic radiography is not specific for pulmonary hypertension, but may demonstrate supportive findings, including cardiomegaly, right-sided heart enlargement, or pulmonary artery dilation. Pulmonary arteries may be tortuous in patients with heartworm disease
The echocardiogram is the gold standard noninvasive diagnostic tool for pulmonary hypertension. The maximal tricuspid valve regurgitation velocity is the most common echocardiographic method used to diagnose systolic pulmonary hypertension. Both subjective and objective assessments are also informative including assessment of the right-sided cardiac structures, transpulmonary artery velocity profiles and maximal pulmonary valve insufficiency velocity.
The most common endothelin antagonists include bosentan, sitaxsentan, and ambrisentan. These oral medications have been shown to improve exercise intolerance, pulmonary arterial pressure, and even pulmonary vascular resistance in people. Side effects in people include dose-dependent hepatotoxicosis, anemia, and birth defects.
Bosentan has been assessed in dogs in experimental settings. In these patients, bosentan was effective and was found to decrease vascular remodeling in induced pulmonary hypertension, improve myocardial function, and decrease ventricular remodeling. Unfortunately, there are no clinical trials of endothelin antagonists in dogs with naturally occurring disease. Endothelin antagonists, while less expensive than prostacyclin analogues, are considered cost prohibitive in veterinary patients.
Phosphodiesterase 5 Inhibitors
There are several phosphodiesterase 5 (PDE5) inhibitors, including sildenafil, tadalafil and vardenafil. These drugs all specifically inhibit PDE5, which is highly concentrated in pulmonary vessels. PDE5 normally breaks down cyclic guanosine monophosphate (cGMP). When PDE5 is inhibited, cGMP concentrations increase and vasodilation is promoted. Sildenafil is a short-acting PDE5 inhibitor. It has been evaluated for treating canine pulmonary hypertension in the clinical setting and has been shown to decrease pulmonary arterial pressure, improve quality of life, and improve survival time. Sildenafil has rare gastrointestinal side effects and, while relatively expensive, may be affordable for many clients. It is considered the drug of choice for treating pulmonary hypertension in dogs. The recommended sildenafil dose is 1 to 3 mg/kg by mouth, every eight to 12 hours.
Tadalafil is a long-acting PDE5 inhibitor. There is a single published case study evaluating a dog treated with tadalafil. The patient was diagnosed with idiopathic pulmonary hypertension and was treated with tadalafil (1 mg/kg orally every 48 hours) in addition to other medications. The patient demonstrated decreased pulmonary arterial pressure and improved clinical signs with tadalafil treatment, but was euthanized 10 days later because of signs of weakness, tremor, and decreased appetite. Ultimately, the clinicians felt the patient suffered systemic hypotension secondary to tadalafil use, but that was not confirmed. While there is some evidence that tadalafil can improve echocardiographic signs and clinical signs in dogs with pulmonary hypertension, this medication should be used cautiously.
Pimobendan (Vetmedin®, Boehringer Ingelheim Vetmedica) and levosimendan are dual mechanism drugs. They exert positive inotropic effects associated with calcium sensitization, as well as vasodilatory effects mediated by PDE3 inhibition. Clinically, pimobendan has been shown to improve pulmonary hypertension secondary to degenerative mitral valve disease (clinical class II). Pimobendan has not been well studied as a single agent therapy in dogs with other clinical classes of pulmonary hypertension and is not considered an effective therapy for those dogs with pulmonary hypertension for any clinical class other than II.
Supportive Care and Treatment of Underlying Conditions
Patients with pulmonary hypertension often require supportive therapy and additional therapies based on the underlying cause of the pulmonary hypertension. These therapies may include oxygen supplementation, treatment of pulmonary disease with antiinflammatory or bronchodilating agents, treatment of neoplasia with appropriate chemotherapy, or treatment of congestive heart failure with diuretics. Patients with thromboembolic disease may benefit from anticoagulant medications and corticosteroids, and patients with heartworm disease may require heartworm adulticide therapy.
The prognosis for dogs with pulmonary hypertension varies and often depends on the underlying cause. Published survival has increased to 91 days, with some patients surviving almost two years. Negative prognostic factors may include advanced functional class, high right atrial pressure, severe right ventricular dysfunction, and increased NT-proBNP values.