ACVIM consensus statement guidelines for the diagnosis, classification, treatment, and monitoring of pulmonary hypertension in dogs

Abstract Pulmonary hypertension (PH), defined by increased pressure within the pulmonary vasculature, is a hemodynamic and pathophysiologic state present in a wide variety of cardiovascular, respiratory, and systemic diseases. The purpose of this consensus statement is to provide a multidisciplinary approach to guidelines for the diagnosis, classification, treatment, and monitoring of PH in dogs. Comprehensive evaluation including consideration of signalment, clinical signs, echocardiographic parameters, and results of other diagnostic tests supports the diagnosis of PH and allows identification of associated underlying conditions. Dogs with PH can be classified into the following 6 groups: group 1, pulmonary arterial hypertension; group 2, left heart disease; group 3, respiratory disease/hypoxia; group 4, pulmonary emboli/pulmonary thrombi/pulmonary thromboemboli; group 5, parasitic disease (Dirofilaria and Angiostrongylus); and group 6, disorders that are multifactorial or with unclear mechanisms. The approach to treatment of PH focuses on strategies to decrease the risk of progression, complications, or both, recommendations to target underlying diseases or factors contributing to PH, and PH‐specific treatments. Dogs with PH should be monitored for improvement, static condition, or progression, and any identified underlying disorder should be addressed and monitored simultaneously.


| Hemodynamic definitions and terminology
Pulmonary hypertension is defined by abnormally increased pressure within the pulmonary vasculature. The criterion standard method for diagnosis of PH is direct assessment of pulmonary arterial pressure (PAP) by right heart catheterization (RHC) and, in humans, PH has been defined as a mean PAP ≥25 mm Hg at rest. 3 A schematic outlining the pathophysiology of PH is shown in Figure 1. Increased PAP is not a defining characteristic of a specific clinical condition but rather an abnormal hemodynamic state associated with numerous, diverse disorders. 4 Increased PAP, in the absence of increased pulmonary vascular resistance (PVR), has several causes requiring different management strategies and having different outcomes, including increased cardiac output, left-to-right shunts, and increased pulmonary arterial wedge pressure (PAWP) secondary to the left-sided heart disease (LHD). Increased PAP associated with increased PAWP (>15 mm Hg in humans 5 ; a surrogate for left atrial [LA] or left ventricular filling pressure), is referred to as postcapillary PH. Postcapillary PH occurs most commonly in dogs with LHD that have increased LA pressure.
It develops because LA hypertension increases the load on the right ventricle and indirectly necessitates the development of higher systolic right ventricular (RV) pressures. Chronic postcapillary PH can lead to pulmonary arterial vasoconstriction and pulmonary vascular disease (PVD), which increase PVR. 6,7 Thus, postcapillary PH can occur in isolation (isolated postcapillary PH [Ipost-PH]) or can occur together with increased PVR (combined postcapillary and precapillary PH; C-PH) as a result of chronic, progressive LHD. In humans, C-PH currently is defined by a pressure difference of ≥7 mm Hg between diastolic PAP and PAWP. 5 An equivalent pressure difference has not been established in dogs. Increased PAP also can be caused by increased PVR and structural pulmonary arterial changes associated with PVD due to a variety of other causes. Increased PAP associated with increased PVR in the absence of increased LA pressure defines precapillary PH (pre-PH).
test for the presence of PH. Definitive diagnosis of PH requires RHC.
Echocardiographic assessment of PH is based largely on characteristic cardiac changes that occur secondary to PH (ie, echocardiographic signs of PH) and by estimating PAP from spectral Doppler tracings.
Because RHC rarely is utilized for definitive diagnosis of PH in dogs, veterinarians rely on echocardiography for diagnosis, classification, and management of dogs with PH.
However, clinicians should be mindful of limitations of the echocardiographic examination (particularly Doppler echocardiography) and of inaccuracy, 8 variability, and imprecision 9,10 potentially encountered when using echocardiography to estimate PAP in individual dogs.
The panel has kept these echocardiographic shortcomings in mind when proposing guidelines and recommendations. Because many echocardiographic signs of PH have not been compared to RHC findings in dogs, we have consulted current echocardiographic guidelines for humans 11,12 and the veterinary medical literature when relevant citations were available to establish these guidelines. The proposed criteria are intended to avoid misdiagnosis and inappropriate treatment of PH that might have lasting impact on the dog and its owner. Lastly, echocardiographic assessment of PH is just 1, albeit important, aspect in the overall clinical assessment of a dog with suspected PH. Echocardiographic findings always should be interpreted within the context of other clinical findings, especially the presence or absence of clinical signs suggestive of PH (Table 1) and right-sided heart failure status, as well as results of concurrent diagnostic testing.

| Echocardiographic signs of PH and estimating PAP
The use of Doppler echocardiography to estimate PAP is crucial to the echocardiographic assessment of dogs with suspected PH. Assuming the F I G U R E 1 Development of pulmonary hypertension, defined as abnormally increased pressure within the pulmonary vasculature, results from increased pulmonary blood flow, increased pulmonary vascular resistance, increased pulmonary venous pressure, or some combination thereof. Normal pulmonary vasculature is comprised of thin-walled arteries, veins and capillaries; a low pressure, low vascular resistance, and high capacitance system. In homeostasis, blood ejected from the right ventricle (RV) into the pulmonary trunk is directed to the right and left pulmonary arteries. The pulmonary arterial pressure remains low in homeostatic conditions by the dense network of pulmonary capillaries that can accommodate rapid transit of large volume of blood arriving from the pulmonary arteries. Following efficient gas exchange at the alveolarcapillary interface, oxygenated blood is then collected by the pulmonary venules that unite to form the veins, which eventually open into the left atrium. Upon complex interactions of genetic and environmental factors, most of which are still poorly understood in dogs, homeostasis of pulmonary circulation can be disturbed. These disturbances (summarized in boxes) can lead to an excessive increase in pulmonary blood flow, increased pulmonary vascular resistance, or increased pulmonary venous pressure. Additionally, there is interplay between these factors*: increased pulmonary blood flow or increased pulmonary venous pressure can lead to increased pulmonary vascular resistance due to pulmonary arterial vasoconstriction, pulmonary vascular disease/remodeling, or both. When the average pulmonary arterial pressure increases above a certain threshold (25 mm Hg is commonly used in humans), PH results. With sustained PH, the RV has to work harder against increases in pulmonary pressures to move blood through the pulmonary vasculature. As a consequence, the RV undergoes structural alterations. Over time, the progressive increase in RV workload can ultimately lead to RV dysfunction and failure, resulting in heart failure (ascites), low output signs, and death. ASD, atrial septal defect; EDD, endothelial-dependent dilatation; LV, left ventricle; NO, nitric oxide; PDA, patent ductus arteriosus; PH, pulmonary hypertension; VSD, ventricular septal defect absence of RV outflow tract obstruction (eg, pulmonary valve stenosis), estimating systolic PAP involves quantifying peak tricuspid regurgitation velocity (TRV), and then derivation of the pressure gradient (PG) between the RV and right atrium using the simplified Bernoulli Equation 2 ). An estimate of right atrial (RA) pressure is added to the calculated PG to yield estimated systolic PAP. Validated methods to estimate RA pressure are unavailable in dogs, and therefore estimates of RA pressure are arbitrary and potentially flawed. 8,10,13 Consequently, we recommend using only continuous wave Doppler measurement of TRV (versus estimated systolic PAP) as a key metric in determining PH probability as long as clinicians are aware that systolic PAP might be underestimated when severe RA hypertension is present.
Measured TRV depends upon many factors including RV function and pericardial restraint 14 in addition to PAP and PVR. Additionally, poor patient cooperation and labored respiration affect measurements. Accurate interpretation of a TRV signal includes consideration of all factors impacting RV systolic pressure. A pulmonary regurgitation (PR) jet also can be used to estimate mean or diastolic PAP. 11,15,16 Applying the simplified Bernoulli equation to spectral Doppler measurements of peak diastolic PR velocity provides an estimate of mean PAP. 16 Similarly, peak diastolic PR jet velocity offers an estimate of diastolic PAP after adding an estimate of RA pressure. 15 Because tricuspid regurgitation has been utilized more commonly, and clinicians conventionally have viewed PH in relation to estimates of systolic PAP, TRV can be considered the primary metric to estimate PAP and the key component to determine the probability of PH in at-risk dogs. Recommended echocardiographic criteria used to help determine the probability of PH are presented in Table 2.
Although specific techniques of echocardiographic image acquisition and measurement are beyond the scope of this consensus statement, Doppler spectra should be well visualized and their shape and contour should comply with known hemodynamic principles. Care should be taken to align the cursor parallel to the direction of flow,  Table 3.
F I G U R E 2 Example measurements of tricuspid regurgitation velocity (TRV) spectra acquired using continuous wave Doppler. A, The solid arrow shows the recommended measurement of TRV. The dense outer edge of the velocity profile (brighter signal) is measured and measurement sof the fine linear signals has been avoided. The dotted arrow represents a measurement that includes the fine linear signals or "feathered edge," which likely overestimates TRV. B, A TRV signal of good quality is shown. Notice the envelope is fully visible, the signal is not overgained (helps to avoid fine linear signals), the sweep speed is increased, and the scale along the vertical axis is nearly filled by the TRV signal. C, Shows 3 TRV signals, 1 of moderate quality (*) that is not completely filled in but can be measured by extrapolation and 2 others of poor quality (#) that are unreliable and should not be measured optimize gain settings, and to measure regurgitant jets at the dense outer edge of the velocity profile while avoiding measurement of fine linear signals, also called the "feathered edge" (Figure 2). [29][30][31] Because tricuspid regurgitation jets can be eccentric, nonstandard imaging planes might be necessary for visualization of tricuspid regurgitation and acquisition of TRV.
In addition to TRV, several echocardiographic signs of PH aid probability assessment for PH. These signs involve 3 anatomic sites: (1) ventricles, (2) pulmonary artery (although pulmonary artery is the commonly used term in clinical practice, the preferred anatomic term for the main pulmonary artery is pulmonary trunk 32 and herein we consider them synonymously), and (3) RA and caudal vena cava (Table 3).
These echocardiographic signs of PH largely involve assessment of the ventricles (left ventricular and RV size and remodeling, 19 Tables 2 and 3 for echocardiographic assessment of PH pertain to the use of a probability-based approach for the assessment PH for all causes of PH (groups 1-6, Table 4). In addition to criteria in Tables 2 and 3 Given the limitations of the veterinary literature (eg, single case reports or small case series, retrospective study design, frequent presence of confounding comorbid conditions contributing to PH, lack of uniform and rigorous diagnostic testing to definitively rule out comorbid conditions, among others), not all panelists agree with provided references to support the disease as the cause of PH. Larger, prospective carefully designed studies will be required to provide the necessary evidence to further refine this classification scheme. b In the veterinary literature, when no underlying cause of PH has been found, PH is often assumed to be "idiopathic." However, it is important to recognize the difference between not finding a cause after an exhaustive diagnostic evaluation and calling a disease idiopathic after a cursory evaluation (see . The first 5 references are considered definitive studies as histopathology documents a pulmonary arteriopathy in the absence of a known cause. c The next 6 references are considered questionable support for IPAH; although no identified cause was found, the diagnostic evaluation may not have been reported or have been incomplete and histologic evaluation was not performed. d Experimental canine studies. e PVOD and PCH can occur in tandem. f In the peer-reviewed veterinary literature, many studies refer to "chronic respiratory/pulmonary disease" or "idiopathic" respiratory disease, or "chronic tracheobronchial disease" without definitive documentation of the specific underlying disorder. 35,[40][41][42]66,85,149 Other listed "definitive" diagnoses may be published without ruling out disease mimics in an exhaustive fashion (eg, thoracic radiography alone can be definitive for collapsing trachea but nondefinitive for bronchomalacia or fibrotic lung disease). Without a criterion standard definitive confirmation (eg, bronchoscopy for bronchomalacia or lung biopsy for pulmonary fibrosis), many of these respiratory diseases are likely inadequately characterized. Additionally, many dogs with disorders associated with PH in humans do not get a specific evaluation for PH; thus the group 3 disorders are likely grossly underestimated. Additionally, disorders which are not clearly documented or are undocumented to cause PH in the dog include pharyngeal collapse, 150 laryngeal collapse, laryngeal paralysis, and epiglottic retroversion. g Although "chronic bronchitis" has been listed as a diagnosis in some canine reports, 18,85 this syndrome alone in the dog is unlikely to cause PH. The term chronic obstructive pulmonary disease (COPD) used in humans encompasses underlying and overlapping conditions such as chronic bronchitis and emphysema. Both cause airflow limitation and dyspnea in people. Canine chronic bronchitis by itself (ie, without concurrent bronchomalacia) does not cause airflow limitation leading to increased expiratory respiratory effort and emphysema is very rare in dogs, thus the term COPD is inappropriate to use in this species. Tracheal and mainstem bronchial collapse and bronchomalacia are common causes of obstructive airway disorders; however, referenced studies proving they cause PH are somewhat limited by many reported dogs having comorbid conditions also known to cause PH. h Angiostrongylus and Dirofilaria are excluded from infectious causes of pneumonia as the pathophysiology of PH is usually multifactorial with these parasitic infections. The term "pneumonia" by itself does not necessarily imply an infectious etiology and care must be taken when interpreting results of studies that do not specifically identify an organism but find compatible radiographic changes or inflammatory cells on airway lavage or histopathology. 35 In humans, hematologic disorders (eg, certain types of anemia, myeloproliferative disorders, and splenectomy), systemic disorders with lung involvement (eg, sarcoidosis, Langerhans cell histiocytosis, vasculitis, etc), metabolic disorders (disorders of impaired cell metabolism, thyroid disease), and other diseases not well classified in another group (eg, compressive lesions such as lymphadenopathy, tumor or fibrosing mediastinitis obstructing the pulmonary arteries, etc) comprise the multifactorial, unclear mechanism group, or both. 148 As these analogous disorders with rare exception either do not occur in dogs or if they occur, may not be documented to cause PH, additional research and modification of these group 6 disorders in dogs will likely be needed. This is a particularly poorly understood category and it is likely that other diseases will be added in the future with additional investigation. l To be classified as 6a, there must be identified diseases in more than 1 of the group 1-5 disorders (eg, group 2 MMVD and group 3b1 ILD) and not just 2 or more types of disease within a single disorder (group 3a1 tracheal collapse and group 3b1a fibrotic lung disease).  160 As in humans, it is expected that evolution of this classification scheme will occur with increased recognition and understanding of underlying conditions.

Recommendations in
The proposed clinical classification of PH in dogs comprises the following 6 groups (  Figure 4) and group 4 ( Figure 5) with group 5 potentially being identified on this initial algorithm or within the group 3 algorithm. The group 1 algorithm (Figure 7) generally used after ruling out disorders in groups 2-6. Critical to appropriate use of the diagnostic algorithms is the understanding that dogs frequently have greater than 1 type of pathology contributing to PH either across groups (eg, a dog with MMVD with interstitial lung disease is encompassed in groups 2 and 3, respectively) or within a group (eg, a dog with tracheal collapse and fibrotic lung disease both fall within group 3). Clinical evaluation must drive the diagnostic approach and make sense in context of localizing disease and pursuit of comorbid conditions. For example, a small breed dog with left-sided heart failure that has inspiratory stridor in addition to rapid, shallow breathing should not have the diagnostic algorithm terminated after diagnosis of group 2c1a disease; instead, further evaluation for an upper airway defect such as extrathoracic tracheal collapse should be pursued. a Thoracic radiographs are frequently obtained before echocardiography and may provide additional findings supportive of underlying PH etiology.

| Recommendations to target underlying diseases or factors contributing to PH
Long-term supplemental oxygen has yet to be evaluated as supportive treatment using randomized clinical trials in people with PH but generally is recommended. 12 A recent large observational study showed benefit in PAH. 176 189,190 • Consensus in 7/7 members of the panel and 5/5 advisory reviewers T7. The group 3b disorders are diverse, some with specific treatments and some in which viable treatment options do not exist.
a. Within group 3b1, fibrotic lung disease to date has no effective treatments, likely reflecting end-stage lesions and lack of understanding of specific triggers. 94,158 In some cases of fibrotic lung disease, PO or inhaled corticosteroids may relieve cough, particularly in the presence of concurrent bronchial changes. 191,192 Dogs with cryptogenic organizing pneumonia receiving early and aggressive treatment with immunosuppressive doses of glucocorticoids may have a good prognosis. 94 Whole lung lavage has been described to treat pulmonary alveolar proteinosis. 193 Corticosteroids are the primary treatment for eosinophilic lung disease. 95,185,186 b. In dogs with group 3b2 disorders in which infection underlies pathology, appropriate antimicrobials are recommended. For example, pneumocystis pneumonia should be treated with high-dose trimethoprim-sulfonamide with or without an anti-inflammatory dose of corticosteroids. 102,194 c. In dogs with group 3b3 diffuse pulmonary neoplasia, consultation with a veterinary oncologist is recommended because options are limited and for most cancers (aside from lymphoma), and prognosis is grave.
• Consensus in 7/7 members of the panel and 5/5 advisory reviewers T11. The reader is referred to guidelines for management of heartworm disease 165  T12. When feasible in group 6b dogs, medical, endovascular, or surgical treatment to address the compressive mass lesion (eg, treatment of blastomycosis, radiation therapy for heart base masses, intravascular stents) is recommended.
• Consensus in 7/7 members of the panel and 5/5 advisory reviewers

| PH-specific treatment
Excessive pulmonary arterial vasoconstriction secondary to a variety of pulmonary arterial endothelial insults develops via the nitric oxide, endothelin, or prostacyclin pathways. 204  Treatment strategies for PH are highly dependent on cause and chronicity of PH. Some PH-specific treatments (eg, pulmonary artery vasodilators such as PDE5i) might lead to acute pulmonary edema in some dogs with PH. Therefore, pulmonary artery vasodilators in some specific situations such as dogs with PH associated with congenital cardiac shunts (group 1d1) or secondary to LHD (group 2) warrants caution.
In dogs with PH associated with congenital cardiac shunts, increased PAP can be caused primarily by increased blood flow through the pulmonary vasculature, reactive pulmonary vasoconstriction, or may occur secondary to PVD. Often it is difficult using echocardiography to discern the relative impact of each of these factors on estimated PAP. Dogs in group 1d1 without substantially increased PVR exhibit left-to-right (systemicto-pulmonary) shunting and will benefit from closure or occlusion of the shunt rather than a pulmonary artery vasodilator. Dogs in group 1d1 with increased PVR might benefit from a pulmonary artery vasodilator, particularly if they are exhibiting bidirectional or right-to-left (pulmonary-tosystemic) shunting and erythrocytosis. Closure will not be possible if PVR exceeds systemic vascular resistance. In some cases, shunt flow may reverse (ie, become left-to-right) after administration of a pulmonary artery vasodilator, thus permitting safer closure or occlusion of the shunt. 55 However, a pulmonary artery vasodilator might induce pulmonary edema in some dogs in this scenario if they have "reactive" or "responsive" pulmonary arteries (or arterioles) and substantial irreversible PVD has not developed.
Similarly, dogs in group 2 may (C-PH) or may not (Ipost PH) have increased PVR (Table 5). In addition to treatment specifically targeting the LHD and LHF, some dogs with C-PH might benefit from a PDE5i in an attempt to alleviate clinical signs. However, similar to dogs in group 1d1, their vascular reactivity or responsiveness to a pulmonary vasodilator is difficult to predict, and pulmonary edema also may ensue. The mechanism of inducing pulmonary edema is similar in dogs in groups 1d1 and 2. In both situations, a pulmonary artery vasodilator might increase right heart cardiac output, acutely increasing pulmo-  26 Although pimobendan has been suggested as a treatment for PH in general, 24,83,105,205,220 to date, there is no direct or clear evidence of its beneficial effects on pre-PH. Previously reported improvements in estimated PAPs in dogs with MMVD might be related to its beneficial effect on lowering LA pressure 221 and thus targeting postcapillary PH. Further study is needed to help clarify pimobendan's role in pre-PH. Thus, the panel does not advocate for or against the use of pimobendan as adjunct treatment in dogs with pre-PH.
Milrinone: Milrinone is an IV PDE3i. It has both PA vasodilating and positive inotropic properties. In experimental canine PH, milrinone improved RV function 222 and decreased mean PAP. 223 Tyrosine kinase inhibitors (eg, toceranib, imatinib): Tyrosine kinase inhibitors (TKI) result in PA vasodilation by inhibiting the activation of platelet derived growth factor by impeding phosphorylation of the platelet-derived growth factor receptor tyrosine kinase. In people, specific TKI are effective at improving refractory PH 224-228 but serious adverse events are common. 228 In dogs, a single study demonstrated imatinib reduced PAP in dogs diagnosed with PH secondary to LHD. 229 Paradoxically, some TKI can induce PH in humans. 230 Consideration of and monitoring for contraindications and adverse events are indicated.
L-arginine: L-arginine is an amino acid that is essential, in conjunction with oxygen, to the production of NO. Oral administration increases surrogate markers of NO in healthy dogs. 231 Although no clinical studies in dogs have demonstrated the benefits of L-arginine in clinical patients, 1 study in experimental canine acute PTE showed L-arginine and sildenafil together were not more beneficial than sildenafil alone. 232 In dogs, there is insufficient information in the literature and anecdotal experience with other PH-specific therapies used in humans (eg, calcium channel blockers, endothelin antagonists, prostanoids, soluble guanylate cyclase stimulators, etc). No recommendations on the use of these medications can be made at the current time.
echocardiograms in clinically stable patients may not be necessary in all dogs with PH.
• Consensus in 7/7 members of the panel and 5/5 advisory reviewers M3. Other complementary diagnostic tests may be considered to guide treatment including thoracic imaging, pulse oximetry, arterial blood gases, N terminal pro-B-type natriuretic peptide, 6MWT, and activity monitors. Although it is recognized that a panel of data reflecting patient status is likely to be superior to any single outcome variable, the optimal means to evaluate patient status is, as yet, unclear. Complementary diagnostic tests may be considered 2 weeks after starting or changing PH-specific treatment, or in patients with underlying disease impacting clinical signs, based on the clinician's discretion.
• Consensus in 7/7 members of the panel and 5/5 advisory reviewers

OFF-LABEL ANTIMICROBIAL DECLARATION
Authors declare no off-label use of antimicrobials.

BOX 2 Specific considerations for monitoring underlying disorders
Group 1 PAH: Dogs in group 1a, 1b, 1c, 1d2, and 1d3 that have an antemortem diagnosis should follow consensus monitoring recommendations above. In group 1d1, some congenital heart diseases may require additional monitoring to guide treatment (eg, Eisenmenger's physiology should have a PCV or hematocrit when clinical signs are present to guide phlebotomy and administration of fluids or hydroxyurea). 54,177 Similar to dogs in group 1d1 and group 2, dogs in group 1' might also develop acute pulmonary edema following administration of a pulmonary artery vasodilator. Thus, if diagnosed antemortem (uncommon), appropriate monitoring (as previously discussed) is warranted following administration of pulmonary artery vasodilators.
Group 2 PH secondary to left-sided cardiac disease: In group 2 dogs, monitoring recommendations often depend on where in the stage of heart disease the dog is classified. If a dog develops postcapillary PH, the cardiac disease is more advanced. In all group 2 dogs, the main points to monitor are the status of heart failure (primarily via thoracic radiography), and renal function and electrolyte status (both assessed by a biochemical profile). Echocardiography may be indicated to assess for adverse complications of left-sided cardiac disease that can result in decompensation of the patient, such as ruptured chordae tendineae, pericardial effusion secondary to an atrial tear, or the development of an acquired atrial septal defect secondary to a tear of the interatrial septum. For dogs with an infectious component to the left-sided cardiac disease, as in group 2a2 and 2c1b, monitoring for changes in the valve leaflets or chamber walls may be accomplished with echocardiography. Serial analysis of cardiac troponin I might be useful in monitoring dogs with a presumptive diagnosis of myocarditis. The reader is referred to the ACVIM consensus statement on MMVD in dogs 161 and a comprehensive review of DCM in dogs 233 for specific monitoring recommendations for the underlying LHD.
Group 3 PH secondary to respiratory disease, hypoxia, or both: In many of the group 3 disorders (eg, 3a, 3b1b, 3b1e, 3b2, 3c), clinical signs can guide titration of medications. In case of acute disease exacerbation or development of new clinical signs, repeating some of the initial diagnostics (eg, imaging) may be warranted. Serial thoracic radiography can be performed to assess for improvement using glucocorticoids in dogs with group 3b1b and 3b1e disorders and in dogs receiving antimicrobials in group 3b2. Dogs in group 3b1, particularly those with fibrotic lung disease (3b1a) and chronic progressive ILDs (3b1d), can be monitored using measurement of arterial blood gas (or pulse oximetry) or a 6MWT. 234,235 Group 4 PH secondary to PE/PT/PTE: Duration of antithrombotic treatment depends if the underlying condition(s) have resolved (in which case antithrombotic treatment should be discontinued following resolution of the thrombus) or are persistent (in which case antithrombotic treatment should continue indefinitely). 169 The reader is referred to recent consensus guidelines for specific anti-thrombotic monitoring and weaning recommendations. 169 Group 5 PH secondary to parasitic disease (heartworm or angiostrongylus infection): Confirmation of efficacy of Dirofilaria immitis adulticidal treatment is most reliably performed using heartworm antigen testing. 165 In dogs with angiostrongylosis, monitoring can be performed by using antigen-based assays or molecular techniques on blood samples. 236 Group 6 PH with multifactorial or unclear mechanisms: For group 6b dogs receiving targeted treatment, thoracic imaging every 1-3 months to evaluate the size of the mass compressing the pulmonary arteries may be considered, with cross-sectional imaging (CT) likely more sensitive to detect changes in mass size than thoracic radiography.