Pulmonary Hypertension

Question 1

Selexipag - MOA and side effects

Answer 1

Prostacyclin-receptor agonist

Headaches - high rate of discontinuation

Question 2

Riociguat - MOA, indication, adverse effects

Answer 2

Guanylate cyclase stimulant
Benefit in inoperable persistent chronic thromboembolic pulmonary hypertension
Well tolerated - syncope most frequently reported side effect
Can’t give with PDE5Is

Question 3

Causes of Group 1 pulmonary hypertension

Answer 3

• Idiopathic
• Heretiable
• Drugs
• PAH associated with CTD, HIV, portal hypertension, congenital heart disease, schistosomiasis
• PAH long term responders to calcium channel blockers
• PAH with features of PVOD
• Persistent PH of the newborn

Question 4

Causes of Group 2 Pulmonary Hypertension

Answer 4

• Left sided heart disease -> heart failure with preserved or reduced ejection fraction
• Valvular heart disease

Question 5

Causes of Group 3 Pulmonary Hypertension

Answer 5

• Lung disease/hypoxia -> obstructive lung disease, restrictive lung disease, hypoxia without lung disease, developmental lung disorders

Question 6

Causes of Group 4 Pulmonary Hypertension

Answer 6

• Pulmonary artery obstruction -> chronic thromboembolic PH

Question 7

Causes of Group 5 Pulmonary Hypertension

Answer 7

• The “others” -> haematological, systemic and metabolic disorders, complex congenital heart disease

Question 8

Notes on hereditary pulmonary hypertension

Answer 8

• 80% hereditary due to BMPR2 mutations (bone morphogenetic protein receptor type 2)
• AD
• Incomplete penetrance, variable expressivity

Question 9

Drugs associated with pulmonary hypertension

Answer 9

• Appetite suppressant -> fenfluramine, dexfenfluramine, methamphetamines
• Dasatinib (may be partially reversible)
• Possibe agents -> chronic use of cocaine, amphetamines, reported in some on interferon alpha, SSRIs (probably not causative but AW worse prognosis)

Question 10

ECHO screening for pulmonary hypertension

Answer 10

• Calculate tricuspid regurgitant jet velocity - probability high if >3.4msec
• Signs of RV overload -> systolic flattening of interventricular septum, hypertrophy RV free wall, as disease progresses -> RV and RA dilatation, TR, Reduced RV outflow acceleration time, enlarged pulmonary artery diameter, enlarged IVC with decreased inspiratory collapse
• Allows assessment of possible contribution from left heart disease
• If findings suggestive of PH and sufficient left heart disease as a cause -> no need to further investigate
• If Left heart disease insufficient to explain findings further investigations
• **Suspected CLD -> **HRCT, lung function, 6MWT
• **Risk factors/history of VTE -> **V/Q scanning
• if an alternative cause cannot be found -> right heart catheter

Question 11

Notes on right heart catheterisation

Answer 11

**Vasoreactivity testing
**- Groups likely to be vasoreaction -> idiopathic, hereditary, drug induced
-Contraindications -> low systolic BP, severe symptoms (Functional Class IV - same as NYHA but WHO)
- Short acting vasodilator given at RHC - nitric oxide, adnosine, inhaled iloprost
- If MPAP decreases by 10mmHg and to <= 40mmHg with increased/unchanged cardiac output -> patient for trial of calcium channel blocker (nifedipine, diltiazem, can trial amlodipine)

Question 12

Notes on endothelin recetor antagonsists

Answer 12

• E.g. bosentan, ambrisentan
• **Adverse effects
• **Hepatotoxicity
• Peripheral oedema - most common
• Teratogenic
• Avoid ambrisentan in concurrent IPF -> increased risk disease progression and hospitalisation

Question 13

Notes on nitric oxide guanosine monophosphate enhancers

Answer 13

**1. PDE5Is
**-Sildenafil -> A/Es headaches, GI upset, flushing, muscle and joint pains
**2. Guanylate cyclase stimulant
**-Riociguat -> benefit in inoperable persistent chronic thromboembolic PH
- Syncope most common adverse effect
- Can’t give with PDEI5s
- **3. Oral prostacyclin receptor agonists
- **-Selexipag
- **4. Parenteral prostanoids
- **- IV epopprostenol - A/Es jaw pain, diarrhoea, flushing, arthralgias. Pump issues - thrombosis, malfunction. Interruption of infusion can precipitate life threatening crisis from rebound PH
- Ilopeost - can be inhaled

Question 14

Indications for referral for lung transplant in pulmonary hypertension

Answer 14

1. Functional class III/IV during escalating therapy
2. Rapidly progressive therapy
3. Use of parenteral prostanoid therapy regardless of functional class
4. Known of suspected pulmonary venoocclusive disease or pulmonary capillary hemangiomas

Question 15

Notes on diagnosis of suspected chronic thromboembolic pulmonary hypertension

Answer 15

• Mechanical obstruction of pulmonary arteries by thrombus which does not resolve -> fibrotic transformation of thrombus, downstream remodelling of smaller vessels
• No linear correlation between degree of mechanical obstruction and haemodynamics
• Should think of this is persistence of symptoms after 3 months of anticoagulation for PE
• Work-up: V/Q scan = screening, typical ECHO features. Diagnosis = RHC

**Management
- Lifelong anticoagulation
- **Confirm operability on CTPA or pulmonary angiogram
- Surgical options - pulmonary endarterectomy, balloon pulmonary angioplasty
- Lung transplant if all else fails
- If inoperable -> medical therapy

Question 16

Notes on risk assessment in pulmonary hypertension

Answer 16