Pulmonary Hypertension Flashcards
What are gold standard diagnostic criteria for pulmonary hypertension?
What are the criteria for breaking down into the subtypes?
Right heart catheter: mean pulmonary artery pressures (mPAP) >20mmHg
Pre-capillary = + PAWP ≤15 + PVR >2
Isolated post-capillary = +PAWP >15 + PVR ≤2
Combined pre + post = +PAWP >15 + PVR >2
Exercised-PH = mPAP/CO slope >3 between rest and exercise
Pulmonary arterial wedge pressure (PAWP)
Pulmonary vascular resistance (PVR) nb. PVR = (mPAP - PAWP)/CO
What are the criteria for isolated post-capillary pulmonary HTN?
mPAP > 20 + PAWP >15 + PVR ≤2
What are the criteria for pre-capillary pulmonary HTN?
mPAP >20 + PAWP ≤15 + PVR >2
What are the criteria for combine pre and post-capillary pulmonary HTN?
mPAP ≥ 20 + PAWP >15 + PVR >2
What are the criteria for exercise-induced pulmonary HTN?
mPAP/CO slope >3 between rest and exercise
How is pulmonary HTN classified by cause?
Group 1-5
1 pulmonary arterial hypertension
- idiopathic
- heritable (BMPR-2 = common mutation)
- associated with drugs/toxins (wt loss drugs, metamphetamines, cancer drugs)
- associated with CTD (particularly Ssc), HIV, portal HTN, congenital heart disease, schistosomiasis
- PAH with features of venous/capillary involvement
- persistent PH of newborn
2 associated with L heart disease
- HF, valvular heart disease, congenital/acquired cardiomyopathy
3 associated with lung disease/hypoxia
- COPD, ILD, hypoventilation (inc OSA with hypoventilation)
- hypoxia without lung disease e.g. altitute
4 associated with pulmonary arterial obstruction
- CTEPH
- Malignancy, arteritis w/o CTD
5 unclear/multifactorial
- sarcoid
- haematological disorders e.g. haemolytic anaemia
- renal failure
- Langerhans
What are causes of type 1 PH and how what are the diagnostic criteria?
1 pulmonary arterial hypertension
- idiopathic
- heritable (BMPR-2 = common mutation)
- associated with drugs/toxins (wt loss drugs, metamphetamines, cancer drugs)
- associated with CTD (particularly Ssc), HIV, portal HTN, congenital heart disease, schistosomiasis
- PAH with features of venous/capillary involvement
- persistent PH of newborn
mPAP >20
+ PAWP ≤15 and PVR >2 (as pre-capillary PH)
What are the causes of type 2 PH and what are the diagnostic criteria?
2 associated with L heart disease
- HF, valvular heart disease, congenital/acquired cardiomyopathy
mPAP >20
+ PAWP >15 and PVR ≤2 (isolated post-cap) or PVR >2 (combine pre and post cap)
What are the causes of type 3 PH and what are diagnostic criteria?
3 associated with lung disease/hypoxia
- COPD, ILD, hypoventilation (inc OSA with hypoventilation)
- hypoxia without lung disease e.g. altitude
mPAP >20
+ PAWP ≤15 and PVR >2 (as pre-capillary PH)
What are the causes of type 4 PH and what are the diagnostic criteria?
4 associated with pulmonary arterial obstruction
- CTEPH
- Malignancy, arteritis w/o CTD
mPAP >20
+ PAWP ≤15 and PVR >2 (as pre-capillary PH)
What are the causes of type 5 PH and what are the diagnostic criteria?
5 unclear/multifactorial
- sarcoid
- haematological disorders e.g. haemolytic anaemia
- renal failure
- Langerhans
mPAP >20
+ PAWP ≤15 and PVR >2 (as pre-capillary PH)
What is the prevalence of PH?
1%
What is the most common mutation associated with PH?
BMPR-2
Autosomal dominant with variable penetrance
Accounts for 70% case of heritable PAH
Which CTD has the highest prevalence of PH?
Systemic sclerosis (5-19%) - screen annually with echo and risk score
What is the leading cause of PH?
Left heart disease
COPD second
What are the symptoms of PH?
SOBOE, fatigue, SOB bending forward (bendopnoea), palpitations, haemoptysis, exercise induced abdo distension and nausea, wt gain from fluid retention, syncope during or shortly after exercise
What clinical findings might you see with PH?
TR/PR, fluid overload, underlying disease
What is Ortner’s syndrome?
Compression of left recurrent laryngeal nerve - causes hoarse voice
What features might you see on ECG in PH?
Signs of R heart dysfunction - p-pulmonale, R axis deviation, RV hypertrophy, RBBB, ST depression/Twave inversion in V1-4 II III avF
What features might you see on echo in PH?
- R heart dysfunction
- Raised systolic PA pressure (PASP or sPAP) - measured as TR pressure gradient + estimated RA pressure
–> note this is not prognostic or reflective of response to treatment/disease progression - Peak TR velocity can be used to separate in low/int/high probability of PH
peak TRV ≤2.8 + no other PH signs on echo = low
peak TRV 2.8 - 3.4 + no other signs or ≤2.8 with other signs - int
peak TRV >3.4 or 2.8 - 3.4 with other signs = high
What might you see on spirometry in PH?
Mild restriction + reduced DLCO (and any underlying lung disease if a cause)
What is vasoreactivity testing in PH? What is considered positive?
- done in idiopathic, heritable or drug-induced PAH.
- give iloprost or nitric oxide
- positive response is decrease in mPAP by ≥10mmHg to get value ≤40mmHg with increased or unchanged cardiac output
- means that can use high dose CCB (nifedipine) to treat
Who should be screened for PH?
Asymptomatic high risk
- systemic sclerosis
- BMPR2 carriers
- 1 degree relatives of pt with heritable PH
- those undergoing liver tx assessment
Symptomatic at-risk
- portal HTN
- HIV
- non-SSc CTD
What is pathophysiology of type 1 PH?
Pulmonary vascular remodelling causes increased resistance (high PVR) and RV dysfunction
How is PAH treated?
Test vasoreactivity + use CCB if eligible (re-assess at 3-6 months after starting)
If not suitable:
+ cardiovascular co-morbidites = oral monotherapy with PDE5i or ERA
- cardiovascular co-morbidities + low/int risk of risk stratification = PDE5i + ERA
+ high risk = PDE5i + ERA + IV/s/c PCA
F/u at 3 months and risk stratify into 4 groups:
- low risk = no change
- low-int risk = add ERA or switch PDE5i to cGMP stimulator
- int-high risk = add IV or s/c PCA +/- evaluate for lung tx
- high risk = as for int-high risk
PDE5i (increases NO levels)
- Sildenafil/Tadalafil
cGMP stimulator (also increases NO)
- Riociguat
Endothelin antagonist (older = more SEs)
- Bosentan/Ambisentan/Macitentan
Prostacyclin analogues (PCA)
- Prostacyclin/Epoprostenol (IV)
- Iloprost (Neb/IV)
- Trepostinil (IV/Neb/s/c)
- Selesipag (oral)
General measures:
- exercise
- anticoag NOT routine (individual asessment)
- diuretics if RH failure
- oxygen if pO2<8
- avoid pregnancy
- consider iron replacement even without anaemia if levels low
How is type 3 PH treated?
- treat underlying lung disease
- exclude VTE, diastolic HF and sleep disorders
- PH ass with COPD rarely severe (can get transient rise is PASP during exacerbation), but with ILD can be severe
- no evidence for vasodilators
- sometimes try PDE5i in very severe ILD + PH
- oxygen can prevent vascular remodelling
How treat type 4 PH?
Anticoag +
1st line: pulmonary endarterectomy (surgery)
2nd line/not eligible for surgery: balloon angioplasty
3rd line: PAH therapies
surgery 3yr survival 90% vs 70 for balloon
What are risk factors for CTEPH?
Previous PE
Young age
Large perfusion deficit
Idiopathic PE
Splenectomy, VA shunt, thyroid disease, malignancy, anti phospholipid syndrome, non-O blood group
Does a normal CTPA rule out CTEPH?
No. But normal VQ does
What are PDE5 inhibitors?
Sildenafil, Tadalafil
What are enothelin receptor antagonists?
Bosentan, Ambisentan, Macitentan
What are prostacylcin analogues?
Protacyclin/Epoprostenol (IV)
Iloprost (IV/neb)
Trepostinin (IV/neb/s/c)
Selesipag (oral)
Side effects of endothelium receptor antagonists
Headache, cutaneous flushing, oedema.
Deranged liver function, leading to cirrhosis and failure (avoid if moderate or severe hepatic impairment). 
Young man with progressive dyspnoea, no pmx and non-smoker. Bilateral creps. Reduced DLCO. Pre-cap pulmonary HTN on RHC. CT shows enlarged mediastinal nodes and thickened interlobular septa. What mutation is associated with this?
EIF2AK4 - associated with pulmonary veno-occlusive disease. Rare cause of pulmonary venules cause pulmonary HTN
What are high risk stratification criteria for patient with PAH?
Signs of RH failure
Rapid progression of symptoms.
Repeated syncope.
Grade 4 WHO criteria
6MWT < 165m
BNP > 800 or NT-BNP > 1100
RA area >26
RA pressure >14
Moderate or large pericardial effusion
Venous SATS <60
Cardiac index < 2
Nb 1 year mortality >20%
What are intermediate risk stratification criteria for patient with PAH?
No signs of RH failure
Slow progression of symptoms.
Occasional syncope.
Grade 3 WHO criteria
6MWT 165-440m
BNP 50-800 or NT-BNP 300-1100
RA area 18-26
RA pressure 8-14
Minimal pericardial effusion
Venous SATS 60-65
Cardiac index 2-2.4
1 year mortality 5-20%
Patient has VQ scan has two large segmental perfusion defects. What is probability of PE?
High risk
Nb large = >75% of segment
Patient has VQ scan has no perfusion defects. What is risk of PE?
Low
Other findings also classified as low:
Non-segmental defect
Defect smaller than CXR opacity
Perfusion defect small subsegmental (<25% of segment)
Two or more matched VQ defects
Large pleural effusion
What symptoms would classify someone as high risk (WHO type 4) pulmonary HTN? And how might this affect management of PAH?
SOB at rest or syncope
If vasoreactivity negative then would start with PDE5i, ERA and IV or s/c PCA
Nb. Positive vaso = decrease mPAP by 10+ to get value <=40 with increased or unchanged CO
Nb. PDE5i = sildenafil, tadalafil
Riociguat = cGMP = similar to PDE5i
ERA (endothelin antagonist) = bosentan, ambisentan, macicentan
PCA (prostanoids) = prostacyclin/epoprostenol (IV), iloprost (IV/neb), trepostonil (IV/sc/neb), selesipag (oral)
What CXR changes might you see in PH?
bulky PA on both sides (look like bulky hilar)
increased heart size
oligaemic lung fields
effusions very unlikely
What is the only cause of pulmonary oedema and effusions in pre-capillary pulmonary HTN?
Pulmonary veno-occlusive disease (part of group 1)
What auscultations findings might you hear in pulmonary hypertension?
Loud second heart sound
What are plexiform and colander lesions?
Plexiform - disorganised proliferation of endothelial cells to from capillary-like plexeus of channels seen in PAH
Colander - small areas of recanalisation in occluding organised thrombus associated with CTEPH
