243 Pulmonary hypertension and pulmonary thomboembolism

Question 1

What is pulmonary hypertension

Answer 1

• (PH) is defined as pulmonary arterial systolic pressure >30mmHg +/- diastolic pressure >19mmHg as estimated by echo of tricuspid or pulmonic regurgitation gradients. - The normal mean pulmonary arterial (PA) is 14mmHg. -

Question 2

How does pulmonary hypertension develop?

Answer 2

• blood flows from RV through PA into network of thin-walled arteries, capillaries and veins, before returning to thin-walled arteries, capillaries and veins, before returning to LA via pulmonary veins. Pulmonary arterial pressure (PAP) is determined by RV cardiac output, pulmonary vascular resistance (PVR) and pulmonary venous pressure - hypertension develops when there is an imbalance between factors that control pulmonary artery vasoconstriction, vasodilation, platelet activation and smooth muscle cell proliferation. -

Question 3

What causes pulmonary vasoconstriction?

Answer 3

• alveolar hypoxia, endothelin-1, and serotonin - Hypoxia- induced vasoconstriction = deoxygenated blood shunting to better ventilated areas of lung. This can lead to PH.

Question 4

What is ET-1? What does it do? How is it linked to PH?

Answer 4

• Endothelin-1 (ET-1) = peptide released from vascular endothelium in response to changes in blood flow, vascular stretch and thrombin concentrations. - ET-1 causes vasoconstriction, stimulates smooth muscle growth, increases collagen synthesis, promotes vascular remodelling, and is increases in people with PH. - Dogs: elevated ET-1 in diseases linked to PH i.e. HW, acquired left heart disease https://www.youtube.com/watch?v=n7BdCrpJuHg

Question 5

What is prostacyclin and thromboxane A2?

Answer 5

• Prostacyclin and thromboxane A2 - arachidonic acid metabolites of PA vascular cells with opposing effects on PA muscular tone. - Prostacyclin = vasodilator, inhibit platelet activation and antiproliferative properties - Thromboxane A2 is vasoconstrictor and platelet agonist. - Platelet derived growth factor (PDGF) => proliferation and migration of PA smooth muscle cells. Expression of PDGF and receptor increased in people with idiopathic PH.

Question 6

What is Nitric Oxide? What does it do?

Answer 6

• NO= vasodilator, inhibitor of platelet activation, and inhibitor of vascular smooth muscle proliferation. - Synthesised from L-arginine and Oxygen by NO synthase enzymes in PA endothelium. - NO activates cyclic guanosine monophosphate (cGMP), causing pulmonary vasodilation. - Vasodilation limited by inactivation of cGMP by phosphodiesterase 5 (PDE5) isoenzyme -

Question 7

What is group 1 PH ?

Answer 7

1. Pulmonary arterial hypertension (PAH) due to pulmonary arteriolar vascular disease: - pulmonary vascular parasitic disease: angiostrongylus vasorum, dirofilaria immitis (-> hyperrtophy & fibrosis) - congenital systemic-to-pulmonary shunt (-> stress endothelium): ASD, PDA, VSD - necrotising vasculitis/arteritis - idiopathic

Question 8

What is group 2 PH?

Answer 8

2. PH with left heart disease (pulm. venous hypertension) - mitral valve disease - myocardial diseae - miscellaneous left-sided heart disease

Question 9

What is group 3 PH?

Answer 9

3. Pulmonary hypertension with pulmonary disease/hypoxemia - COPD - high-altitude disease -interstitial pulmonary fibrosis - neoplasia - reactive pulmonary artery vasoconstriction - tracheobronchial disease

Question 10

What is group 4 PH?

Answer 10

4. Pulmonary hypertension due to thrombotic +/- embolic disease - thromboembolism: cardiac dz, C-steroid, DIC, Endocarditis, hyperA, IMHA, indwelling venous catheters, neoplasia, pancreatitis, PLN/PLE, sepsis, surgery, trauma - Dirofilaria immitis

Question 11

What is group 5 PH?

Answer 11

5, Miscellaneous - compressive mass lesions: neoplasia, granuloma - polycythemia vera - chronic IMHA

Question 12

What is the common signalment of breeds with PH?

Answer 12

• small breed and middle-to older-aged coinciding with predisposed aetiologies such as degenerative MVD and chronic pulmonary disease

Question 13

What is the cause of vascular resistance as a complication of pulmonary disease?

Answer 13

The increased vascular resistance as a complication of pulmonary disease is adaptive response of the lung to improve the matching of ventilation and perfusion (V/Q) through hypoxic vasoconstriction.

Question 14

What are the clinical signs and findings on physical examination?

Answer 14

• exercise intolerance, cough, dyspea, syncope - abnormal lung sounds, cyanosis, +/- ascites - pulmonary crackles, wheezes, and harsh/inc resp sounds - left or right sided murmurs - split hear sound - Cats will be dysneic, jugular distension and right sided systolic heart murmur

Question 15

How is PH diagnosed? What velocities/pressures indicate PH? What is mild, moderate, and severe?

Answer 15

• echo diagnoses PH, not usually right heart catheterisation. peak regurgitant flow velocity of tricuspid regurgitation (TR) or pulmonic insufficiency (PI) - When no pulmonic stenosis, the regurgitant velocitey can allow estimation of PA pressures using modified Bernoulli equation: pressure gradient = 4X peak velocity) - Peak TR velocity >2.8 m/s (pressure gradient >31 mmHg) or PI velocity >2.2 m/s (pressure gradient > 19mmHg) suggests PH - mild PH = 31-50 mmHg - mod PH = 51-75 mmHg - Severe PH = >75mmHg

Question 16

What findings on T-rads support PH?

Answer 16

• R. heart enlargement - pulmonary artery dilation +/- infiltrates - MVD patients <15kg demonstrate vertebral heart scale short axis of >5.2 vertebrae (v) and length of sternal contact >3.3 v had predictive accuracy of 85.9% for detecting PH

Question 17

How is PH treated?

Answer 17

• Aim at underlying aetiologies Endothelin antagoinist and prostacyclin analogs value is not determined: - endothelin antagonists: bosentan, ambrisentan, macitentan - prostacyclin analogs: berprost, epoprosenol, iloprost - phosphodiesterase type V inhibitors (PDE5-I) commonly prescribed for PH in dogs. Sildenafil (Viagra), tadalafil (Cialis) and vardenafil (Levitra) cause vasodilation by increasing pulmonary vascular cGMP. This causes increased NO concentrations. - PDE5-I reduce cardiac remodelling, apoptosis, fibrosis, ventricular hypertrophy, and improve left-heart function in people. - Sildenafil at 1-2 mg/kg PO 8-12h

Question 18

How is group 2 & 3 PH managed?

Answer 18

Question 19

WHat is tadafil? is it useful to manage PH?

Answer 19

Tadalafil is long-acting PDE5 inhibitor

• single case study of idiopathic PH treated with tadagil (1mg/kg PO q 48h) which improved signs, and decreases PAP

Question 20

What PDE3 inhibitor can gelp Group 2 PH?

Answer 20

• Pimobendan PDE3 inhibitor and calcium sensitised
• treatment in dogs withMVD reduced NT-proBNP levels.
• improve QOL

Question 21

What anti-thrombosis medication can be used?

Answer 21

• aspirin or clopidegrol
• Imatinib (Gleevec) inhibits activation of platelet derived growth factor PDGF and inhibits PDGF receptor. 6 dogs with CHF and PH from MVD or HW were treated at 3mg/kg dose PO q24h for 30 days, and imprved their TR velocity, LA size, and plasma atrial natriuretic peptide concentration

Question 22

What is the progosis for canine PH?

Answer 22

• variable and depends on underlying cause
• long term prognoss
• Sildenafil increases survival to 91days-2years.

Question 23

What is pulmonary thromboembolism?

What is the pathophysiology of PTE? What are complications?

Answer 23

= partial or complete obstruction ofPAor its branches by thromi secondary to other disease processes

• Pathogenesis of PTE is based on endothelial damage, blood flow stasis and hypercoagulable states
• PTE results in hypoxemia, bronchoconstriction, ventilation-perfusion mismatch, and hyperventilation
• Hemodynamic complications depend on occlusion and pre-existing cardiac conditions.
• Further complications : atelactasis, pulmonary oedema, and pleural effusion.

Question 24

What are the common clinical signs?

What are the findings on t-rads and arterial blood gases?

Answer 24

• most common dyspnea, tachypea, and lethargy
• T-rads: nonspecific, ranging from focal pulmonary infiltrates to normal findings

Arterial blood gases: hypoxemia, hypocapia and increased alveolar-arterial oxygen tension gradient.

Question 25

What are conditions associated causing thromboembolic state?

Answer 25

- Cardiac disease - C-steroid administration - DIC - Endocarditis (pulmonic/tricuspid valve) - Hyperadrenocorticism - IMHA - indwelling venous catheters - Neoplasia - Pancreatitis - PLN/PLE - Sepsis - Surgery - Trauma

Question 26

How is PTE managed/treated?

Answer 26

- Limit thrombus growth and prevent recurrence - Anticoagulants, antiplatelet therapy and thombolytics used - Unfractionated heparin (100 to 300 IU/kg per dose SC q6-8h, adjusting dosage to keep activated partial thromboplastin [aPTT] at 1.5 - 2 times baseline) or low molecular weight heparin (dalteparin 100-150 IU/kg q 8hin dogs and 100-180 IU/kg SC q 8-24h in cats. - O2, judicious iV fluids, sildenafil and bronchodilators - Aspirin is beneficial for thromboprophylaxis in IMHa and PLN. - Aspirin dosage ate 0.5mg/kg PO q24h in dogs and 5-81 mg/dose PO q 3 days in cats. - Clopidogrel 2-3mg/kg PO q 24h in dogs and 18.75 mg/dose PO q 24h in cats.