Pulmonary Hypertension Flashcards
Definition of PH.
Mean PAP >25 mmHg at rest.
Definition of post-PH.
Increased PAP associated with increased PAWP (>15 mmHg in humans), a surrogate for LA/LV filling pressure.
Definition of pre-PH.
Increased PAP associated with increased PVR in the absence of increased LA pressure.
Pathophysiology of PH (main groups).
-increased pulmonary blood flow
-increased pulmonary vascular resistance (PVR)
-increased pulmonary venous pressure
Increased pulmonary blood flow.
Congenital L-R shunt
-PDA
-ASD
-VSD
-aortopulmonary window
Increased PVR.
-Pulmonary endothelial dysfunction (vasoconstriction, alteration of NO - prostacyclin pathways)
-Pulmonary vascular remodelling
-Perivascular inflammation
-Vascular luminal obstruction
-Increased blood viscosity
-Arterial wall stiffness
-Lung parenchymal destruction
Increased pulmonary venous pressure.
-Left heart disease (LV systolic/diastolic dysfunction, inflow obstruction, valvular disease)
-Compression of a large pulmonary vein
Common clinical findings.
Syncope (especially exertional)
Dyspnoea (especially at rest)
R-CHF (ascites)
Cyanosis/pallor
High echocardiographic probability of PH in dogs.
-TR Vmax >3.4 m/s, echo signs of PH at 1 anatomical site
-TR Vmax 3.0-3.4 m/s, echo signs of PH at 2 anatomical sites
-TR Vmax <30. m/s, echo signs of PH at 3 anatomical sites
How to estimate systolic PAP using TRV.
-Measure peak tricuspid regurgitation velocity
-Derive RV-RA pressure gradient using the simplified Bernoulli Equation (PG = 4 × velocity [m/s]2)
-Add estimated RA pressure
Assumes the absence of RV outflow tract obstruction
Use of TRV vs estimated systolic PAP to quantify PH.
Systolic PAP may be underestimated when presence of RA hypertension
Factors affecting measured peak TRV.
RV function
Pericardial restraint
Patient cooperation
Labored respiration
What information does peak PR velocity provide?
-Estimated mean PAP.
-Estimated diastolic PAP (once estimated RA pressure added).
Anatomic sites of echo signs of PH.
-Ventricles (flattening of IVS, underfilled LV, RV hypertrophy, RV systolic dysfunction)
-PA (PA dilatation, peak PR velocity >2.5, RPAD index <30%, RV outflow acceleration time <52-58 ms or acceleration time to ejection <0.30, systolic notching of RV outflow profile)
-RA/CauVC (RA or CauVC dilatation)
Common physical exam findings.
-Murmur
-Split/loud S2
-Abdominal distension
-Jugular distension/pulsation
-Cyanosis
-Abnormal breathing pattern (insp effort, exp effort, paradoxical)
-Abnormal lung sounds (muffled, crackles, wheezes, bronchovesicular sounds)
Proposed classification of pulmonary hypertension in the dog.
1) Pulmonary arterial hypertension (including pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis)
2) Left-heart disease
3) Respiratory disease, hypoxia, or both
4) Pulmonary emboli, thrombi, thromboemboli
5) Parasitic disease
6) Multifactorial or unclear
Differentials for PA hypertension.
-idiopathic
-heritable
-drugs/toxins
-congenital cardiac shunts
-pulmonary vasculitis
-pulmonary vascular amyloid deposition
Differentials for left-heart disease causing PH.
-LV dysfunction (DCM, myocarditis)
-acquired valvular disease (DMVD, valvular endocarditis)
-congenital heart disease (MVD, mitral stenosis, aortic stenosis)
Differentials for respiratory disease or hypoxia causing PH.
-chronic obstructive airway disorders (tracheal or mainstem bronchial collapse, bronchomalacia)
-primary pulmonary parenchymal disease (interstitial lung disease, infectious pneumonia, diffuse pulmonary neoplasia)
-obstructive sleep apnoea
-chronic altitude exposure
-developmental lung disease
-miscellaneous (bronchiolar disorders, bronchiectasis, emphysema, pneumonectomy)
Differentials for parasitic causes for PH.
-Angiostrongylus
-Dirofilaria
Multifactorial/unclear differentials PH causes.
-clear evidence of 2 or more underlying groups
-masses compressing the pulmonary arteries (neoplasia, granuloma)
-unknown
Strategies to decrease the risk of progression or complications of PH.
-exercise restriction
-prophylaxis (respiratory pathogens, parasitic disease)
-avoid pregnancy
-avoid altitude
-avoid elective procedures/anaesthetics
Treatment of PH (Group 1).
-closure/occlusion of L-R shunts (or shunts that become L-R with vasodilators)
-periodic phlebotomy or hydroxyurea treatment in R-L shunting cases
Treatment of PH (Group 2).
-manage left-heart disease
-PDE5i not indicated as first-line treatment (due to post-PH)
Treatment of PH (Group 3).
-treat underlying respiratory disease (cough suppression, sedation, oxygen, control of infection and inflammation; BOAS management)
-general strategies (environmental modification, weight management, avoid triggers)
Treatment of PH (Group 4).
-prompt use of antithrombotics (LMWH/riveroxaban preferred over PO antiplatelet medications)
-plasminogen activators (in systemic hypotension/collapse)
Action of PDE5i.
-Augment the vascular NO pathway
-Targets pre-PH by reducing PVR
Clinical findings vs echo findings with sildenfil treatment.
-improvement of clinical signs, QOL, exercise capacity, and decreased estimated PAP compared with baseline
-TRV might not decrease despite observed clinical benefits (possibly because pulmonary blood flow might increase as PVR decreases, thus resulting in little change in PAP)
Sildenafil dosing.
-short half-life (q8 hour dosing)
-rectal administration can be considered
Alternatives to sildenafil, compared.
Tadalafil:
-longer half-life (q24h dosing)
-improved compliance
-lower cost?
-equivalent effect based on a randomized double-blinded study
Pimobendan for PH in dogs.
Pimobendan
-oral PDE3i
-positive inotropic and systemic vasodilatory properties
- shown to improve RV systolic function following a single oral dose in healthy dogs
-no clear evidence of benefit for pre-PH
Milrinone for PH in dogs.
Milrinone
-IV PDE3i
-PA vasodilating and positive inotropic properties
-improved RV function and decreased mea PAP in experimental canine PH
TKI for PH in dogs.
Toceranib, Imatinib
-Tyrosine kinase inhibitors
-PA vasodilation (inhibits 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 but serious adverse events are common. Paradoxically, some TKI can induce PH in humans
-in dogs, a single study demonstrated imatinib reduced PAP in dogs diagnosed with PH secondary to LHD
L-arginine for PH in dogs.
L-arginine
-amino acid
-essential (in conjunction with oxygen) to NO production
-oral administration increases surrogate markers of NO in healthy dogs
-1 study in experimental canine acute PTE showed L-arginine and sildenafil together were not more beneficial than sildenafil aloneC
