Australian Doctor 19th April issue | Page 23

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Box 7 . Recommended blood tests for all patients

• FBC , liver and renal function tests .

• Brain natriuretic peptide ( BNP ) or N-terminal prohormone of BNP .

• Viral hepatitis and HIV serology .

• Antinuclear antibody , extractable nuclear antigen .

• Thyroid function tests .

are either measured or calculated during the procedure , with key variables listed in table 2 . Other important measurements for prognostication appear in box 8 .

In pure PAH ( Group 1 PH ), the expected RHC results are an elevated mean pulmonary artery pressure ( greater than 20mmHg ), elevated PVR ( greater than 2 Wood units ) and normal pulmonary artery wedge pressure ( less than 15mmHg ). However , in real world practice , there are significant complexities to analysing RHC results . For example , a patient with SSc , AF , hypertension and emphysema may have PH from multiple mechanisms ( Groups 1 , 2 and 3 PH ). Their RHC may show an elevated PVR and an elevated pulmonary artery wedge pressure , which would be reported as combined preand post-capillary PH . Delineating the predominant driver of the PH in such cases is important and is best assessed by the multidisciplinary team at a specialist PH centre .

MANAGEMENT

IDENTIFYING the cause of PH is critical to management decisions because certain interventions may be beneficial for one group but ineffective , or even harmful , in others .

Group 1 pulmonary hypertension — specific therapies for pulmonary arterial hypertension

PAH therapies target the pathways of the pulmonary vasodilator drugs , nitric oxide , endothelin and prostacyclin . Their mechanisms of action and side effects appear in table 3 . Patients with severe disease may be prescribed one drug that targets each pathway , often referred to as a ‘ triple therapy ’.

DIURETICS AND FLUID MANAGEMENT Loop diuretics , thiazide diuretics and mineralocorticoid receptor antagonists can be used as monotherapy or in combination to treat hypervolaemia . Advise patients to regularly monitor their body weight and encourage them to seek medical attention if there has been significant weight gain , as recommended for heart failure patients in general ( 1-1.5kg in 24 hours or more than 2kg over five days ). 25 Fluid balance can be challenging in patients with PH as hypovolaemia can have the deleterious consequences of reduced cardiac output and blood pressure because of reduced preload .

Figure 4 . Clinical appearance of acrosclerotic piecemeal necrosis of the first digit in a patient with systemic sclerosis .

Table 2 . Right heart catheter measurements and definition of pulmonary arterial hypertension

Right heart catheter measurement

Mean pulmonary artery pressure

Mean pulmonary artery wedge pressure ( also known as pulmonary capillary wedge pressure )

rehabilitation program is recommended for those who are established on appropriate pulmonary vasodilator drugs and are clinically stable . 3

OXYGEN Long-term oxygen therapy is recommended in non-smoking PH patients with a partial pressure of oxygen of less than 60mmHg on arterial blood gas measurement . However , this recommendation is based on evidence in patients with COPD . There are no data to suggest long-term oxygen therapy has any sustained benefits on the course of disease in patients with PAH . 3

Definition in pulmonary arterial hypertension

Greater than 20mmHg Less than 15mmHg

Pulmonary vascular resistance Greater than 2 Wood units

VACCINATIONS Like management for patients with other chronic cardiopulmonary comorbidities , being up to date with vaccination against influenza , Streptococcus pneumoniae and SARS-CoV-2 is recommended . 3

ADVANCED CARE PLANNING PAH remains an incurable condition with a high mortality rate . Patients with PAH may deteriorate gradually or experience sudden death . Outcomes following CPR in patients with PAH are poor . One recent retrospective study assessing outcomes of PAH patients experiencing in-hospital

Box 8 . Other important measurements for prognostication

• Cardiac output and cardiac index . The normal range for cardiac index is 2.5-4L / min / m 2 .

• Right atrial pressure ( mmHg ).

• Oxygen saturation of venous blood in the pulmonary artery ( also known as mixed venous oxygen saturation ).

cardiac arrests showed return of spontaneous circulation in only 25 % ( versus 70 % for non-PAH patients ) and a mortality rate of over 95 %. For those with a pulseless-electrical activity cardiac arrest , which was the most common rhythm found , mortality was 100 %. 27 Therefore advanced care planning , understanding the patient ’ s values and involvement of palliative care when appropriate are key pillars in PAH management .

Group 2 and 3 pulmonary hypertension — left heart disease and lung disease

The most important management advice in patients with Group 2 and Group 3 PH is to treat the underlying heart and lung conditions . ET-1 receptor antagonists have been shown to cause harm in patients with Group 2 and 3 PH , such as pulmonary oedema and worsening hypoxaemia , without leading to any improvements in survival .

Group 4 pulmonary hypertension — chronic thromboembolic pulmonary hypertension

CTEPH is the only form of PH where interventional and / or surgical treatment may be indicated . Surgical

Table 3 . Summary of pulmonary vasodilator drugs , their side effects and adverse drug reactions Name

Mechanism of action

Breuckmann F et al . BMC Dermatol 2004 / CC BY 2.0 / bit . ly / 3TvFbPB

Common side effects / adverse drug reactions

Nitric oxide soluble guanylate cyclase ( sGC ) cyclic guanosine monophosphate pathway

Sildenafil Tadalafil

Phosphodiesterase type 5 inhibitor ( PDE5i )

• Headache

• Flushing

• Epistaxis

• Interactions with protease inhibitors used for HIV

Administration notes

• Oral

• Do not use with nitrates

Riociguat sGC stimulator • Similar to PDE5i • Never combine with PDE5i Endothelin pathway Ambrisentan

Bosentan

Macitentan

Prostacyclin pathway Epoprostenol

Preferential endothelin A ( ET-A ) receptor antagonists ( ERA )

ET-A and ET-B receptor ERA

ET-A and ET-B receptor ERA

Prostacyclin analogue

• Teratogenic

• Pedal oedema

• Teratogenic

• Elevation in liver transaminases

• CYP enzyme inducer and drug – drug interactions with anticoagulants , highly active antiretroviral therapy

• Teratogenic

• Anaemia to 80g / L or less

• Headache

• Flushing

• Jaw pain

• Diarrhoea

• Hypotension

• Complications from permanent tunnelled central venous catheter

• Oral

• Oral

• Oral pulmonary endarterectomy ( PEA ) is recommended for accessible proximal thrombus and can increase fiveyear survival from 53 % ( without PEA ) to 83 % with surgery . However , PH persists or recurs after PEA in 17-31 % of patients . 28

For CTEPH patients with inoperable disease , balloon pulmonary angioplasty ( BPA ), a percutaneous vascular intervention , can be considered . A single BPA treatment may consist of repeat procedures , with several weeks between each procedure .

The ESC / ERS guidelines recommend that patients with CTEPH receive lifelong anticoagulation with vitamin K antagonists , such as warfarin . 3 Studies assessing direct oral anticoagulants ( such as rivaroxaban ) have shown bleeding rates comparable to warfarin , but increased rates of recurrent VTE . 3

Group 5 pulmonary hypertension — unclear mechanisms

There is a paucity of positive randomised controlled trials assessing the use of pulmonary vasodilators in Group 5 PH . Treating the underlying disorder is recommended .

SPECIAL CIRCUMSTANCES

Pregnancy and contraception

ALTHOUGH there have been significant improvements in maternal and fetal outcomes , maternal mortality is still high in PAH , ranging from 11-25 %. 3 For those who survive , pregnancy may accelerate disease progression . The incidence of maternal cardiac complications , ICU admission and neonatal mortality , preterm birth , small for

• Never abruptly stop or pause an epoprostenol infusion in the community

• Pulmonary hypertension centres usually provide patients on continuous infusions with contact information for the relevant hospital staff in case of acute issues with their pump and / or central venous catheter

EXERCISE Low-intensity exercise in patients with PAH ( and CTEPH ) is safe and leads to improved six-minute walk distance , WHO-functional classes and quality of life measures . 26 A supervised

Selexipag

Prostacyclin receptor agonist

• Headache

• Jaw pain

• Diarrhoea

• Nausea

Adapted from European Society of Cardiology / European Respiratory Society 2022 guidelines 3

• Oral