Pulmonary hypertension associated with left-sided heart disease in dogs

What is pulmonary hypertension?

Pulmonary hypertension (PH) refers to abnormally high pressure within the pulmonary vasculature. In human medicine, it is defined as a mean pulmonary arterial pressure of ≥25 mmHg at rest (Bach et al., 2006; Borgarelli et al., 2015; Galiè et al., 2016; Reinero et al., 2020). The American College of Veterinary Internal Medicine (ACVIM) consensus statement divides PH into six different groups according to its underlying cause (Reinero et al., 2020).

PH associated with left-sided heart disease is the most common form of PH encountered in dogs. According to the ACVIM consensus statement, it is also known as class 3 of PH. It is mainly caused by an increase of pulmonary venous pressure as a result of increased left atrial pressure (Stepien, 2009; Bussadori, 2023).

PH can develop with any condition that causes persistently increased left atrial pressure. It is a particularly well recognised complication of myxomatous mitral valve disease (MMVD), which is usually seen in more advanced cases. In affected dogs, PH can contribute to the development of right-sided heart failure and is associated with a poorer prognosis (Serres et al., 2006; Kellihan and Stepien, 2007; Menicotti et al., 2021; Tangmahakul et al., 2022).

How does PH develop?

Several different conditions can lead to PH by increasing pressure on the left side of the heart. These include left ventricular dysfunction, such as dilated cardiomyopathy and myocarditis; acquired or congenital valve disease, such as MMVD, mitral dysplasia or mitral stenosis; and congenital or acquired obstructions affecting left-sided inflow or outflow, such as cor triatriatum sinister or subaortic stenosis (Reinero et al., 2020; Bussadori, 2023).

MMVD is the most common acquired cardiopathy in dogs (Häggström, 2004) and is a frequent cause of increased left-sided filling pressures. Borgarelli et al. (2015) described the prevalence of PH of 39% in dogs who were in stage B2 and C of MMVD and associated the presence of PH with significantly shorter survival time and poorer prognosis. Dogs with PH also had more advanced disease and significantly larger left atrial chambers.

In its early stages, PH associated with left-sided heart disease is “passive” as elevation in pulmonary venous pressure is a direct sequela of increased left atrial pressure. This type of PH is also called “isolated” postcapillary PH. At this stage, pulmonary arteries are not yet involved in the remodelling process and there is no increased pulmonary vascular resistance (Bussadori, 2023; Corda et al., 2023).

With time, chronically elevated pulmonary venous pressures will cause local and systemic increase of several biomarkers including angiotensin II, tumour necrosis factor and endothelin-1 which, together with an impaired nitric oxide-mediated vasodilation, will increase pulmonary vascular resistance and result in irreversible remodelling of pulmonary veins and arteries (pre- and postcapillary combined PH).

Chronic respiratory diseases such as tracheal collapse, chronic bronchitis or interstitial lung disease are also commonly encountered in small dogs with MMVD and may contribute to development of PH (Borgarelli et al., 2015; Jaffey et al., 2019).

Clinical evaluation

In human medicine, the gold standard for diagnosing PH is right heart catheterisation. This is rarely performed in veterinary patients because it is invasive and generally requires general anaesthesia, which can itself alter cardiac output and therefore influence the measurements (Kim et al., 2020; Menicotti et al., 2021).

In literature, PH has been classed as mild, moderate or severe according to pressure gradient obtained from measurement of tricuspid regurgitation velocity that estimates pulmonary systolic arterial pressure (Reinero et al., 2020).

Nevertheless, clinicians need to keep in mind that the assessment based solely on tricuspid regurgitation velocity or pressure gradient can be misleading, as it has been found to correlate poorly with results obtained with right heart catheterisation in dogs affected with MMVD ACVIM stage B2 (Menciotti et al., 2020).

According to ACVIM consensus recommendations, assessment of severity of PH should also include clinical signs, which can be difficult in dogs with severe left-sided heart disease as clinical signs associated with PH are often not significantly different from those of the underlying disease (Bussadori, 2023). Symptoms indicating high probability of PH include exertional syncope, exercise intolerance, respiratory distress at rest and cardiogenic ascites (Kellihan and Stepien, 2010; Visser et al., 2019; Reinero et al., 2020).

Echocardiographic assessment

Doppler echocardiography is an essential non-invasive tool for assessing the probability of PH in dogs. The tricuspid regurgitation velocity is particularly useful, but it should always be interpreted alongside other echocardiographic findings.

In the absence of right ventricular outflow tract obstruction, the tricuspid regurgitation pressure gradient reflects the pressure difference between the right ventricle and right atrium and can therefore provide an estimate of pulmonary arterial systolic pressure. The pressure gradient is calculated from the tricuspid regurgitation velocity using the simplified Bernoulli equation, and estimated right atrial pressure should then be added to obtain an estimate of pulmonary arterial systolic pressure (Chetboul, 2016; Visser et al., 2019; Reinero et al., 2020; Corda et al., 2023).

However, clinicians need to keep in mind several other factors that can influence tricuspid regurgitation velocity such as right atrial pressure, right ventricular systolic function, pericardial restraint and patient’s poor cooperation that can result in laboured respiration.

According to ACVIM consensus, tricuspid regurgitation velocity “cut off” for intermediate or high probability of PH is velocity higher than 3.4 m/s (Reinero et al., 2020).

Pulmonary regurgitation velocity can be used to estimate mean and diastolic pulmonary arterial pressure. A peak early diastolic pulmonary regurgitation velocity of <2.5 m/s is generally considered normal (Chetboul, 2016; Bussadori, 2023).

Look beyond the tricuspid regurgitation velocity

One of the most important points when assessing probability of PH is not to rely on the tricuspid regurgitation velocity or pressure gradient alone. To be able to properly estimate probability of PH, other cardiac structures and Doppler findings should also be assessed (e.g. pulmonary artery size and distensibility index, pulmonary flow profiles and insufficiency, right ventricular appearance and function, vena cava enlargement, interventricular septal flattening, etc.; Boon, 2011; Visser et al., 2016; Visser et al., 2019; Reinero et al., 2020; Boon, 2023; Corda et al., 2023).

Importantly, the absence of right-sided heart enlargement does not completely rule out PH (Chetboul, 2016; Boon, 2023).

Patients with PH due to left heart disease usually have left-sided heart enlargement and left ventricular transmitral diastolic flow pattern can vary from restrictive to pseudonormal in early stages of postcapillary PH due to increased left ventricular filling pressures.

At this stage, tricuspid regurgitation pressure gradient usually stays ≦60 mmHg.

As disease progresses and PH becomes more combined (pre- and postcapillary), filling of the left heart decreases, resulting in a flow pattern of impaired relaxation whilst tricuspid regurgitation pressure gradient increases (>60 mmHg) (Bussadori, 2023; Boon, 2023).

Severe left ventricular underfilling, which is commonly encountered in other forms of precapillary PH, is usually not seen in PH associated with left-sided heart disease (Reinero et al., 2020).

Treatment options for patients with PH associated with left-sided heart disease

In patients with severe PH, any type of physical exertion should be avoided as it increases the chance for exertional syncope and, in severe cases, sudden cardiac death. In acute settings, oxygen supplementation is useful in almost all types of PH apart from that associated with Eisenmenger’s physiology (Bussadori, 2023).

Medical treatment should be aimed at treating the underlying disease (e.g. left-sided congestive heart failure), but it is also vital to determine the major component of PH. If PH is mainly postcapillary, treatment with phosphodiesterase (PDE) 5 inhibitors (e.g. sildenafil) that act as pulmonary vasodilators is likely to increase venous congestion and lead to development of pulmonary oedema (Corda et al., 2023).

Unless there is unequivocal left atrial enlargement, it is unlikely for the PH to be due to left-sided heart disease. For that reason, left atrial enlargement is very often used in practice for echocardiographic distinction between precapillary and postcapillary PH (Reinero et al., 2020; Corda et al., 2023). In dogs with postcapillary (isolated) PH, pimobendan, a PDE 3 inhibitor, has been shown to be beneficial in lowering tricuspid regurgitation pressure gradient, likely through decrease of pulmonary vascular resistance and left ventricular end diastolic pressure, and it should also improve biventricular systolic function (Bussadori, 2023).

Takeaway message

PH associated with left-sided heart disease is relatively common in dogs with advanced left-sided heart disease. When echocardiographically assessing these patients, it is important not to rely purely on the tricuspid regurgitation velocity or pressure gradient. The size and function of the pulmonary artery, right heart, left atrial size, transmitral flow pattern and other echocardiographic findings should all be considered together with the clinical signs to assess the probability of PH.

Perhaps most importantly, identifying the predominant component of PH is essential. Distinguishing predominantly postcapillary PH from PH with a significant precapillary component can help guide treatment and avoid drugs that could potentially worsen pulmonary congestion.

References

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