Pulmonary Vascular Disease Flashcards
(33 cards)
Define PH (diagnostic requirements and treatment threshold)
- Normal resting mean pulmonary arterial pressure (mPAP) 14mmHg
- PHT = 2 SD above normal/mean ≥ 20mmHg (at rest)
- Assessed via right heart catheterisation
- Treatment threshold ≥ 25mmHg
What is the pathophysiology of PH?
- Differs between groups
- Key features below lead to raised pulmonary vascular resistance and ultimately right heart failure
- Vasoconstriction
- Remodelling of pulmonary vessel wall
- Medial hypertrophy of distal pulmonary arteries +/- fibrotic change
- Thrombosis
- In PAH there is an imbalance between:-
- Nitric oxide
- Prostacyclin (potent vasodilator and platelet inhibitor)
- Thomboxane A2 (potent vasoconstrictor and platelet agonist)
What are the presenting features of PH?
Primarily due to RV dysfunction
- Exertional dyspnoea
- Due to inability to increase cardiac output with exercise
- Chest pain (right heart angina)
- Fatigue and weakness
- Syncope/pre-syncope
- Due to fall in systemic BP on exercise
- Palpitations
- Peripheral oedema and other signs of right-sided fluid overload
What are the examination findings in PH?
- RV heave
- RV third heart sound
- Pansystolic murmur (tricuspid regurgitation)
- Diastolic murmur (pulmonary insufficiency)
- Raised JVP with giant V waves
- Hepatomegaly/ascites/peripheral oedema
- Cyanosis
- Features of causative disease
- Scleroderma: telangiectasia, digital ulceration, sclerodactyly
- Congenital heart disease or ILD: clubbing
- Stigmata of CLD
What are the classes of PH?
- Pulmonary Arterial Hypertension (PAH)
- PHT due to left-heart disease
- PHT due to lung diseases and/or hypoxia
- CTEPH (chronic thromboembolic PHT) and other pulmonary artery obstructions
- PH of unclear/multifactorial mechanisms
What are the subclassifications of PH?
- PAH
1.1. Idiopathic (IPAH)
1.2. Heritable (HPAH) eg. BMPR2 mutation
1.3. Drug and toxin induced (DPAH)
1.4. Associated PAH (APAH -CTD, HIV, portal hypertension, congenital heart disease, Schistosomiasis)
1.5. PAH long-term responders to CCBs
1.6. Pulmonary veno-occlusive disease and/or pulmonary capillary haemangiomatosis
1.7. Persistent PAH of the newborn - PHT due to left-heart disease
2.1. HFpEF
2.2. HFrEF
2.3. Valvular disease
2.4. Congenital/acquired cardiovascular conditions leading to post-capillary PHT
2.5. Congenital/acquired pulmonary vein stenosis - PHT due to lung diseases and/or hypoxia
3.1. COPD
3.2. ILD
3.3. Other pulmonary diseases with mixed restrictive and obstructive patterns
3.4. Sleep disordered breathing
3.5. Alveolar hypoventilation disorders
3.6. Chronic exposure to high altitude
3.7. Developmental abnormalities - CTEPH and other pulmonary artery obstructions
4.1. CTEPH
4.2. Other pulmonary artery obstructions – angiosarcoma, other intravascular tumours, arteritis, congenital pulmonary artery stenosis, parasites (hydatidosis) - PHT due to unclear/multifactorial mechanisms
5.1. Haematological disorders – chronic haemolytic anaemia, myeloproliferative disorders, splenectomy
5.2. Systemic disorders – sarcoidosis, LAM, neurofibromatosis
5.3. Metabolic disorders – glycogen storage disease, Gaucher’s disease, thyroid disorders
5.4. Others – pulmonary tumoural thrombotic microangiopathy, fibrosing mediastinitis, chronic renal failure (with/without dialysis), segmental pulmonary hypertension
What are the functional classification for PH?
- Class 1 – no physical activity limitation
- Class 2 – slight physical activity limitation (comfortable at rest, light activity does not cause symptoms)
- Class 3 – marked physical activity limitation (comfortable at rest, less than ordinary activity causes symptoms – undue dyspnoea, fatigue, chest pain, near syncope)
- Class 4 – inability to carry out any physical activity without symptoms, signs of right heart failure, symptoms at rest and worsen with activity
What are the investigations and findings for PH?
CXR
* Enlarged pulmonary arteries
* Enlarged cardiac silhouette
* Pruning (loss) of peripheral vessels
ECG
* Right arterial dilatation
* Right axis deviation
* RVH and strain
ABG
* Slight hypoxia
* Slight hypocapnia
* Fall in O2 sats on exertion
PFTs
* Can be normal
* Can show mixed restrictive and obstructive disease
* Reduced TLCO – late in disease course
* Abnormal due to underlying aetiology (ie obstructive in COPD, restrictive in ILD)
HRCT
* Perform to exclude underlying disease
V/Q Scan/CTPA
* Performed to exclude CTEPH
* V/Q more sensitive than CTPA (normal/low probability on V/Q excluded CTEPH)
Echocardiogram = most useful screening tool
* Enlarged right-sided cardiac chambers
* Paradoxical IV septal movements and TR
* Pericardial effusion – suggests poor prognosis
* Tricuspid regurgitant jet – can estimate systolic PAP (with estimated RAP from IVC). This can estimate probability of PAH:-
* TR jet ≤2.8m/s (or not measurable): low probability
* TR jet ≤2.8m/s with other PHT signs: intermediate
* TR jet 2.9-3.4m/s: intermediate
* TR jet ≥3.5m/s: high
Right-Heart Catheterisation – gold-standard diagnostic test
* Used to asses:-
* PAP
* Pulmonary capillary wedge pressure
* Cardiac output (via Swann-Ganz catheter/thermodilution/Fick)
* Can also assess
* Left-to-right intracardiac shunt
* Vasodilator responsiveness
- Incremental doses of short-acting vasodilators (inhaled NO, IV epoprostenol, IV adenosine
- Positive response: drop in mean PAP by >10mmHg to < 40mmHg with unchanged/increased cardiac output
6 Minute Walk Test
* Used to objectively assess exercise capacity
* Distance <300m and desaturation >10% indicate poor prognosis
CPET
* Reduced O2 uptake at anaerobic threshold and peak exervise are reduced in relation to disease severity
Blood Tests
* HIV
* TSH
* ACE
* Autoantibodies (if CTD suspected) – anti-centromere, anti SCl-70, anti RNP
* Thrombophilia screen (in CTEPH)
What are the key values for right heart catheterisation in PH?
- Mean Arterial Pulmonary Pressure ≥20 -> PHT present
- Pulmonary Arterial Wedge Pressure (PAWP) >15 = post-capillary PHT
- Due to left-sided heart problem (Group II)
- Pulmonary Arterial Wedge Pressure (PAWP) ≤15 = pre-capillary PHT
- Due to pulmonary vasculature (Group I, III, IV and V)
What are the important genetic and drug causes for PAH?
Genetic
* BMPR2 mutation
* ALK-1
* Endoglin
* Sox17
* EIF2AK4
Drugs
* Chemo – dasatinib
* Methamphetamines
* Aminorex (diet tablet)
What are the features of low-risk stratified PAH?
Signs of RV Failure Absent
Progressive Symptoms No
Syncope No
WHO Functional Class I + II
6MWD >440m
CPET Peak VO2 >15 (>65%)
VE/VCO2 slope <36
BNP <300 (<50)
ECHO/cMRI RA are <18cm2
No pericardial effusion
Haemodynamics RAP <8
CI ≥2.5
SvO2 >65%
What are the features of intermediate-risk stratified PAH?
Signs of RV Failure Absent
Progressive Symptoms Slow
Syncope Occasional
WHO Functional Class III
6MWD 165-440m
CPET Peak VO2 11-15 (35-65%)
VE/VCO2 slope 36-44.9
BNP 300-1400 (50-300)
ECHO/cMRI RA are 18-26cm2
No or minimal pericardial effusion
Haemodynamics RAP 8-14
CI 2-2.4
SvO2 60-65%
What are the features of high-risk stratified PAH?
Signs of RV Failure Present
Progressive Symptoms Rapid
Syncope Repeated
WHO Functional Class IV
6MWD <165m
CPET Peak VO2 <11 (<35%)
VE/VCO2 slope ≥45
BNP >1400 (>300)
ECHO/cMRI RA are >26cm2
Pericardial effusion
Haemodynamics RAP >14
CI <2.0
SvO2 <60%
Describe the medications available for PAH?
Calcium Channel Blockers (CCBs)
* Indication
- IPAH
- Positive response to vasodilator challenge at RHC
- Not used with negative vasodilator challenge
* Options
- High dose nifedipine (120-240mg daily)
- Diltiazem (240-720mg daily)
- Amlodipine (20mg daily) – can be used if intolerant to above or if RV function impaired
- Verapamil no used due to negative inotropic effects
* Monitoring
- Required after 3-4 months to ensure treatment response via repeat RHC
* Side effects
- Hypotension, oedema
Phosphodiesterase Type-5 Inhibitors (PDE5-I)
* Indication
- Group 1 PHT – IPAH, APAH (CTD, congenital heart disease)
- CTEPH
- NYHA functional class II and III
* Options
- Sildenafil (oral, TDS)
- Todalafil (oral, OD)
* Side effects
- Headache, flushing, epistaxis, nasal congestion
- Avoid in combination with nitrates (sever hypotension)
Riociguat – Soluble Guanylate Cyclase Stimulators (sGCs)
* Indication
- Inoperable CTEPH
- IPAH
- APAH (CTD)
* Mechanism
- Enhances cGMP
Prostanoids/Prostacycline Analogues (PCA)
* Overview
- Doubles time on transplant list
- Improves transplantation outcomes
- Tolerance develops to IV therapy – increasing dose requirements over time
* Indication
- IPAH
- APAH (scleroderma)
* Side effects
- Headache
- Jaw pain
- Diarrhoea
- Flushing
- Nausea
- Arthralgia
* Options
- Epoprostenol
- Continuous IV infusion (portable pump or tunnelled line)
- Pump failure -> life threatening
- Treprostinil – not routinely prescribed due to price
- Iloprost – given IV or nebulised)
Prostacyclin IP Receptor Agonist (eg Selexipag)
Endothelin Receptor Antagonists (ERA)
* Indication
- IPAH
- APAH (CTD, HIV)
* Options
- Bosentan (IPAH, APAH-CTD), Eisenmenger’s) - monitor LFTs monthly
- Abrisentan (IPAH, APAH-HIV/CTD)
- Macitentan
What are the therapy guidelines for PAH (Group 1)
- Consider vaso-reactivity
* Vaso-reactivity positive -> CCB
* Vaso-reactivity negative -> Not for CCB - Consider cardiopulmonary comorbidities (risk of LVF, obesity, HTN, DM, CAD, parenchymal lung disease)
* Cardiopulmonary comorbidities present -> oral monotherapy (PDE5-I or ERA)
* Cardiopulmonary comorbidities not present -> risk assess - Risk assessment, initiate treatment, then reassess
* Low or intermediate risk -> ERA + PDES-I
* High risk -> ERA + PDES-I and IV/SC PCA - Reassess risk
* Low risk -> continue current therapy
* Intermediate-low risk -> Add PRA or switch PDE5-I to sGCs
* Intermediate-high or high risk -> Add IV/SC PCA and/or evaluate for lung transplantation
What are the therapy guidelines for Group 4 PH (CTEPH)
- Lifelong Anticoagulation
- Assess for operability
- If technically operable
* Acceptable risk/benefit -> pulmonary endarterectomy
- If persistent symptomatic PH -> targeted medical therapy (riociguat)
* Non-acceptable risk/benefit -> targeted medical therapy (riociguat) - If technically non-operable
* Targeted medical therapy (riociguat) or
* Balloon pulmonary angioplasty - If persistent severe symptomatic PH despite all above -> refer for transplantation
What are the general management options available for PH?
Medications
* Anticoagulation – CTEPH and most IPAH
* LTOT (target pO2 >8 during rest/exercise/sleep
* Diuretics – can help with peripheral oedema, but can reduce pre-load
* Digoxin – useful in improving cardiac output acutely in IPAH
* Antiarrhythmics – treat underlying arrhythmias
* IV iron – IDA common, important to treat as worsens outcomes. Avoid oral as poorly absorbed
* Immunisations – annual influenza, one-off pneumococcal
* Contraception – pregnancy poorly tolerated, high mortality (30-50%)
Surgical Treatments
* Pulmonary Thromboendarterctomy - treatment of choice for proximal CTEPH
* Atrial Septostomy – palliative/pre-transplant procedure for syncope/severe RV failure, creates a R-L shunt bypassing pulmonary circulation
* Balloon Pulmonary Angioplasty – for distal CTEPH
* Transplantation
Describe the pathophysiology of PE (source and haemodynamic effect)
Source
* 75% from lower limb/pelvic deep venous system
* 20% of leg thombi embolise (higher incidence of above knee than below knee)
* Can develop in right heart following MI
* Paradoxical emboli enter arterial system (usually via PFO) -> cerebral ischaemia
- Cause of stroke in the young
* Septic emboli: found in IE and associated with intraventricular septal defects, AV shunts and CV access
Haemodynamic Effects
* Small clots travel distally -> pleuritic pain + lung infarction
- Commonly multiple, bilateral and in lower lobes (greatest blood flow)
* Large clots can lodge at bifurcation of PA -> haemodynamic compromise
- In the young, pulmonary vasculature has large capacity
- PAP only rises when 50% of vascular bed has been occluded (less in older/multimorbid patients)
- As PAP rises, RV afterload increases -> increase in RV end-diastolic pressure
- RV fails as PAP reached 40mmHg (acutely)
- RV failure causes reduced pulmonary blood flow -> reduced LV filling -> reduced systemic blood pressure
- RV failure worsened by inadequate filling (dehydration, hypovolaemia, erect)
- Arterial hypoxia occurs (due to several factors including reduce CO)
- Death occurs from circulatory collapse (from inability of RV to maintain adequate CO)
What are the major and minor risk factors for PE?
Major risk factors
* Surgery
- Major abdominal/pelvic
- Orthopaedic (especially lower limb)
- Post-operative ICU
* Obstetrics
- Pregnancy (higher with multiple births)
- C-section
- Pre-eclampsia
* Malignancy
- Pelvic/abdominal
- Metastatic/advance
* Lower limb problems
- Fractures
- Varicose veins
* Reduced mobility
- Hospitalisation
- Institutional care
- Long haul flight
* Previous proven VTE
Minor risk factors
* CVS
- Congenital heart disease
- CCF
- HTN
- CV access
- Superficial venous thrombosis
* Oestrogens
- OCP – especially 3rd generation oestrogen-containing pills
- HRT
* Miscellaneous
- Occult malignancy (CUP)
- Neurological disability
- Thrombotic disorders
- Obesity
- IBD
- Nephrotic syndrome
- Dialysis
- Myeloproliferative disorders
- Behcet’s disease
Regarding cancer and PE, what are the rates of PE being first presentation. And how should cancer be investigated/excluded?
- Occult malignancy/cancer of unknown primary
- Present in 7-12% of patients presenting with idiopathic/unprovoked PE
- For patients not known to have cancer:-
- Physical examination
- Bloods (FBC, U+E, LFT, clotting)
- Do not offer further investigations unless they have relevant clinical symptoms or signs
Describe thrombophilia and PE (what, when to test, timing of testing, when not to test)
Inherited Thombophilias
* 25-50% of patients with VTE have inherited thrombophilia
* Examples: antiphospholipid syndrome (APS), anti-thrombin II/protein C/Protein S deficiency, prothrombin gene mutation, Factor V Leiden (FVL present in 5% of population, 20% of patients with thrombosis)
- These usually require additional risk acquired risk factor to cause VTE)
* Do not treat with DOAC if suspicious of APS -> increases thrombosis risk
When to Test
* Recurrent VTE
* Young (<40) patients with no obvious risk factors
* First-degree relative with VTE
* Thrombosis secondary to: pregnancy, OCP, HRT
* Thrombosis at unusual site: cerebral, mesenteric, portal, hepatic veins
Timing of Testing
* Can be done on anticoagulation: Factor V Leiden, prothrombin gene mutation
* Need to be off anticoagulation: APS, anti-thrombin II/Protein C/Protein S deficiency
When not to Test
* Routinely
* Lifelong anticoagulation
* Provoked VTE
Describe the Well’s Score for PE
- Clinical Feature and Score
- Signs/symptoms of DVT: 3
- PE likely diagnosis: 3
- HR >100: 1.5
- Immobilisation >3 days or surgery in last 4 weeks: 1.5
- Previous VTE: 1.5
- Haemoptysis: 1
- Malignancy: 1
- Likelihood of PE
- PE unlikely: ≤4 points
- PE likely: >4 points
Describe the different investigations for PE
ECG
* Sinus tachycardia (most common)
* AF
* RBBB
* RV strain (anterior T-wave inversion, S1Q3T3)
CXR
* Excludes other pathology
* Small effusion in 40% (80% exudative, 20% transudative)
* Focal infiltrates
* Segmental collapse
* Raised hemidiaphragm
ABG
* Can be normal (in young and healthy patients)
* Hypoxia (with hypocapnia from hyperventilation) and increased A-a gradient
Bloods
* D-dimer: highly sensitive, poor specificity – therefore only good for excluding PE
* BNP – levels in acute PE reflect severity of RV strain
* Troponin – elevated levels in acute PE are associated with worse prognosis
CTPA
* Gold-standard diagnostic investigation, 95% sensitive
* Also can provide alternative diagnosis
* Can detect embolism in 6th order pulmonary vessels – unclear significance
* Provides RV/LV ratio:-
- ≤ 1 = normal
- 1.1-1.5 = moderate RV dilatation
- >1.5 = severe RV dilatation
Isotope Lung (V/Q) Scanning
* Main uses:-
- Pregnancy
- Renal failure
- Allergy to contrast
* Classification
- High probability ≥80%
>2 large mismatched segmental perfusion defects or
Arithmetic equivalent of moderate and/or large defects
- Intermediate probability (20-79%)
1 moderate or 2 large mismatched segmental perfusion defects or
Arithmetic equivalent of moderate and/or large defects
- Low probability (<20%)
Nonsegmental perfusion defects (effusion, cardiomegaly, elevated diaphragm)
Any perfusion defect with substantially larger CXR abnormality
Extensive matched ventilation and perfusion defects with normal CXR and some areas of normal perfusion elsewhere
Any number of small perfusion defects with normal CXR
- Normal
No perfusion defects
* Interpretation
- Normal = no PE
- Low or intermediate pre-test probability with low probability scan = PE excluded
- High pre-test probability with high probability scan = PE diagnosed
- Other = further imaging required
Leg Ultrasound
* Can be useful if DVT present to avoid further imaging
Conventional Pulmonary Angiogram
* Rarely used
* Only used in specialist centres where catheter-directed thrombolysis can be performed
CT Venography
* Emerging procedure
* Combined with CTPA to image pelvic leg veins simultaneously
Echocardiogram
* Diagnostic in submassive and massive PE
* Can assess for RV strain/failure
Describe PESI
- Parameters
- Age = 1 point per year
- Male = 10 points
- Cancer = 30 points
- Heart failure = 10 points
- Chronic lung disease = 10 points
- HR >110 = 20 points
- SBP <100 = 30 points
- RR >30 = 20 points
- Temp <36 = 20 points
- Altered mental state = 60 points
- Sats <90% on RA = 20 points
- Interpretation
- ≤ 65 = Class I
- 66-85 = Class II
- 86-105 = Class III
- 106-125 = Class IV
- > 125 = Class V
