Pulmonary Hypertension: Are You Missing the Diagnosis?
ACVIM 2008
Heidi B. Kellihan, DVM, DACVIM (Cardiology)
Madison, WI, USA

Definition

Pulmonary hypertension (PH) is a persistent, abnormal elevation in pulmonary systolic or diastolic pressure greater than ~ 30/19 mmHg.1-5

Causes of Pulmonary Hypertension

Pulmonary hypertension in dogs can be primary (idiopathic) or occur secondary to various diseases including: vascular obliterative diseases such as dirofilariasis and pulmonary thromboembolism; primary structural pulmonary disease such as pulmonary fibrosis, pneumonia, and neoplasia; hyperviscosity; reactive pulmonary arterial vasoconstriction; degenerative mitral valve disease and left-sided congestive heart failure (CHF); or congenital cardiac abnormalities such as reversed patent ductus arteriosus (rPDA).

Clinical Presentation of Dogs with Pulmonary Hypertension

The clinical presentation of dogs with symptomatic PH includes cough, dyspnea, lethargy, syncope or collapse episodes, exercise intolerance, an auscultable murmur, and abdominal distension (ascites). In our study of 22 dogs with PH, this was the breakdown of presenting complaints to the Veterinary Cardiology Service:6

1.  Cough: 77% (n=17)

2.  Respiratory distress/ "raspy" breathing/ referral for ausculted pulmonary crackles: 45% (n=10)

3.  Lethargy: 32% (n=7)

4.  Syncope or collapse: 32% (n=7)

5.  Exercise intolerance: 23% (n=5)

6.  Ausculted murmur (alone): 9% (n=2)

7.  Abdominal distension (ascites): 9% (n=2)

8.  Multiple presenting complaints: 73% (n=16)

Signalment

The majority of dogs in our study of natural occurring PH were elderly females of small body size. Forty-five percent of the dogs in the study were terrier breeds. Chronic pulmonary diseases that predispose to PH are reported to be more common in terrier breeds7 but the predominance of female dogs in our study had not been previously reported.

Physical Examination

Murmurs are ausculted in the majority of dogs with PH. These murmurs are often associated with mitral and/or tricuspid insufficiency. In our study, 80% of the dogs had murmurs, 15% had a lone mitral insufficiency murmur, 5% had a lone tricuspid insufficiency murmur, and 60% had both a mitral and tricuspid insufficiency murmur. Split or abnormally loud second heart sounds were ausculted in 20% of our study dogs.

Respiratory auscultation often reveals abnormal findings. In our study, abnormalities included: pulmonary crackles (70%), wheezes (5%), and harsh or increased respiratory sounds (20%). Cyanosis is also an abnormality found in some patients with PH.

Diagnosis of Pulmonary Hypertension

Doppler echocardiography provides a non-invasive and readily available method of diagnosing PH in conscious animals and is now the method of choice to diagnose naturally-occurring PH in veterinary patients. Peak flow velocity and associated gradients of tricuspid regurgitation (TR) or pulmonic insufficiency (PI) are often used to diagnose PH. This method allows rapid, non-invasive estimation of pulmonary pressures in dogs, but accuracy of predicted pressure gradients depends on operator skill and experience and the ability of the dog to tolerate the examination. A peak TR velocity > 2.8 m/s (peak TR gradient > 31mmHg) or a peak PI velocity > 2.2 m/s (peak PI gradient > 19 mmHg) were considered to be abnormally elevated and indicative of PH.2,4,6 Dogs can be categorized as having mild PH (31mmHg-50mmHg), moderate PH (51-75mmHg) and severe PH (>75mmHg).2,6 The addition of the right atrial pressure (if known) to the TR gradient theoretically provides the most accurate prediction of pulmonary systolic pressure, but right atrial pressure is not routinely measured in dogs.

Pulmonary artery flow profiles have been used in dogs and humans to estimate the severity of the PH.2,4,6,9 In our study, the pulmonary artery flow profile categorizations did not always correctly associate with the severity of the calculated gradient at presentation. Nonetheless, the lack of normal pulmonary artery flow profiles recorded at presentation suggests that identification of an abnormal flow profile may be potentially valuable in supporting a diagnosis of PH, but the usefulness of this variable to monitor the effects therapy is not apparent.

Other echocardiographic findings have been utilized to support the diagnosis of PH in dogs, and they include: right ventricular systolic time intervals4,6,8, right-sided tissue Doppler imaging (TDI)10, main pulmonary artery-to-aorta ratios,10 presence of right ventricular hypertrophy, presence of septal flattening, and the index of myocardial performance (Tei).11

Treatment

The goals of treatment for PH is to identify the underlying cause, treat any underlying etiologies and sequelae (i.e., CHF), alleviate the PH directly (if needed), and improve the patients' quality of life. In people, multiple treatments have been postulated to directly improve PH. In dogs, only sildenafil has been evaluated in treating PH.3,6 Most of the medications used in humans either have a low incidence of success in treating PH (i.e., calcium-channel blockers), are cost-prohibitive for our patients (i.e., endothelial antagonists {bosentan} cost: $50,000/year), or are impractically administered (i.e., continuous IV infusion of prostacyclin).

Sildenafil citrate (Viagra®) is a highly selective phosphodiesterase type V inhibitor that causes pulmonary artery vasodilation by increasing pulmonary vascular concentrations of cyclic guanosine monophosphate (cGMP). Increased concentrations of circulating pulmonary vascular cGMP cause vasodilation by increasing the activity of endogenous nitric oxide.Sildenafil was well tolerated in the dogs in our study (dose: ~1mg/kg PO q 8-12 hours),6 and both owners and veterinarians reported clinical improvement in dogs receiving sildenafil for PH. Improvement in clinical signs appears to be the most reliable indicator of success of therapy. Pulmonary artery pressures assessed by TR and PI did not change significantly after sildenafil treatment as a whole or by disease subgroup (i.e., heart disease vs. pulmonary disease vs. rPDA). This differs from the findings in a recent study3 and studies performed in humans,12-15 which have demonstrated a significant reduction of pulmonary artery pressure when treated with sildenafil. In summary, sildenafil did not significantly lower the degree of measurable PH in dogs on our study, yet clinical improvement and increased quality of life was seen with sildenafil treatment despite lack of significant change in other variables.

Outcome

In our study, survival times ranged from 8 to 734 days. Based on this series of 22 dogs with PH treated with sildenafil, if dogs survived the first week of therapy, the probability of survival to 3 months after initiation of therapy was 95%. There was an 84% probability of survival at 6 months and a 73% probability of survival at 1 year after initiation of therapy.

References

1.  Fleming E, et al. Compend Contin Educ Pract Vet. 2006; October: 720;

2.  Johnson L, et al. J Vet Intern Med. 1999;13:440;

3.  Bach JF, et al. J Vet Intern Med. 2006;20:1132;

4.  Schober KE, et al. J Vet Intern Med. 2006;20:912;

5.  Pyle RL, et al. Intern J Appl Res Vet Med. 2004;2:99;

6.  Kellum HB,et al. J Vet Int Med. 2007 Nov-Dec;21(6):1258;

7.  Corcoran BM, et al. Vet Rec. 1999;144:611;

8.  Uehara Y. J Vet Med Sci. 1993;55:307;

9.  Johnson L. Clin Tech Small Anim Pract. 1999;14:231;

10. Serres F, et al. J Vet Intern Med. 2007 Nov-Dec;21(6):1280;

11. Baumwart RD, et al. J Vet Intern Med. 2005 Nov-Dec;19(6):828;

12. Michelakis ED, et al. Circulation. 2003;108:2066;

13. Galie N, et al. N Engl J Med. 2005;353:2148;

14. Humpl T, et al. Circulation. 2005;111:3274;

15. Ghofrani HA, et al. Lancet. 2002;360:895.

Speaker Information
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Heidi Kellihan, DVM, DACVIM (Cardiology)
Madison, WI


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