Pulmonary hypertension (PAH) in rheumatic disease 4.17/5 (6)

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Pulmonary hypertension (PH) is a serious condition where blood from the heart experiences increased resistance to the blood vessels of the lungs (lung arteries). This causes the pressure to rise in the pulmonary arteria. Thus, the heart (right ventricle) must pump at increased strain. Eventually, heart failure may occur.

Disease Causes

Thickening of the blood vessel walls (hyperplasia of intimate and hypertrophy of smooth muscle cells) can occur as a complication of a systemic connective tissue disease (especially Systemic sclerosis), HIV infection, congenital conditions, certain medications or without a known underlying disease (idiopathic pulmonary hypertension) (PH Group 1). Heart failure (in the left part of the heart as a result of heart disease is a relatively common cause (PH group 2), chronic disease of the lung tissue, sleep apnea and prolonged stay at high altitudes are also a cause (Group 3). Chronic blood clots in the lungs (pulmonary embolism) (Group 4) and blood disorders or unclear causes constitute group 5 (reference: Simonneau G, 2013).


Pulmonary hypertension (PH) occurs without special reason (idiopathic) or associated with diseases, especially at Systemic sclerosis (in 7-16%) (reference: Aithala R, 2017), less often by MCTD (4%) (reference: Gunnarsson R, 2013), SLE (1%), Sjøgren`s syndrome (2%) and Myositis.


  • Heavy breathing (dyspnea)
  • Fainting (syncope) on exertion
  • Fatigue / exhaustion
  • Chest pain, cough, coughing up blood (haemoptysis)
  • Swelling (edema) in bones, enlarged liver (hepatomegaly) are signs of severe pulmonary hypertension affecting blood circulation and organs such as the heart and lungs (reference: Pahal P, 2021).
  • Hoarseness can occur (Ortner's syndrome) due to an enlarged pulmonary artery that presses on the recurrent nerve and causes paralysis of the vocal cords (reference: Shahul HA, 2014).
  • Raynaud's phenomenon (corpse fingers)


Pulmonary hypertension (PAH): Diameter of the pulmonary artery (blue arrow) exceeds the diameter of the aorta (red arrow): Rajaram S, Thorax, 2014. CC BY-NC 4.0

Medical history should cover current symptoms (see above) and predisposing diseases and signs, such as Raynaud's phenomenon (connective tissue diseases), abnormal heavy breathing on exertion, known lung disease, risk factors for blood clots (Antifosfolipid syndrome with more).

Clinical examinations may show signs of congestion and a visible pulse in the jugular veins (v. jugularis), swelling in the legs (peripheral oedema), marked second heart sounds on auscultation, enlarged liver and spleen (hepatosplenomegaly) and signs of systemic sclerosis (stiff skin on the hands and around the mouth ) or other relevant underlying disease (see Causes of disease above).

Blood tests. There are no special tests. An elevated NTproBNP (N-terminal pro brain peptide) is often seen as a sign of overload of the right heart ventricle. If the underlying cause of PH is unclear, screening is also recommended antinuclear factors (ANA) for systemic connective tissue disease. By suspect Systemic sclerosis are specific scleroderma antibodies including anti-polymerase III relevant. HIV and thyroid disease may need to be ruled out with tests.

Imaging. In the investigation of the symptoms is often done CT examination of lungs: If one demonstrates that the diameter of the pulmonary artery (pulmonary artery) is abnormally large (≥29mm), or that this is larger than the ascending aorta, pulmonary hypertension can be suspected. CT of the lungs can also help distinguish Group 1 from Group 3 (chronic lung disease). Signs of an enlarged right atrium of the heart (X-ray chest shows that the right ventricle/atrium is enlarged in the retrosternal space) also strengthen the suspicion of pulmonary hypertension. CT with pulmonary embolism protocol or pulmonary angiography (X-ray examination) and scintigraphy (nuclear medicine) are considered if the cause of the disease is unclear (rule out blood clots in the lungs/pulmonary embolism).

ECG may be normal if right-sided failure is not present. With right-sided cardiac strain, right axis deviation is seen: R / S >1 in lead V1, incomplete or complete right bundle branch block. P-pulmonary in lead II and rhythm disturbances.

Lung function tests. There is often a reduced DLCO, but a normal FVC. The ratio FVC%/DLCO% is thus increased. Ratio values ​​greater than 2 increase the possibility that pulmonary hypertension is present. If there are lung symptoms and an FVC%/DLCO% ratio less than 1,4, disease in the lung tissue (interstitial lung disease, ILD) is more likely.

6 minutes walking test is often done as a prognostic indicator and to assess the individual effect of treatment. However, the test assumes normal or stable walking function. Falling below 330-380 metres/6 minutes may indicate an unfavorable prognosis.

Echo Doppler (Ultrasound heart)/echocardiography. The diagnosis of pulmonary hypertension is most often suspected when an ultrasound examination of the heart is performed (echocardiography/Doppler). Borderline elevated pressures are, however, an uncertain sign, and the stated pressure by echocardiography can vary in relation to the real pressure by +/- 10 mmHg. Echocardiography estimates it systolic (upper) the pressure (cardiac catheters measure the average pressure). An echocardiographically calculated systolic thickness of 40 mm Hg may correspond to an average pressure on cardiac catheter examination of more than 25 mm Hg, which is above the limit for pulmonary hypertension (≥ 20 mm Hg). Values ​​above 40-50 mmHg on ultrasound examination should therefore be followed by right-sided heart catheterisation (see below) which ensures or denies whether pulmonary hypertension is present. Severe pulmonary hypertension is suspected if the systolic pulmonary pressure exceeds 60 mm Hg. The pressure that the heart pump must create for the main artery (aorta) is measured by the ejection fraction (EF) and is normally more than 55% when there is no heart failure. Screening annually with ultrasound of the heart/echo doppler in risk groups which is recommended for systemic sclerosis. This is because symptoms are often overlooked in the beginning, and early treatment improves the prognosis.

DETCT calculator can be of help in choosing who should undergo a cardiac catheter examination (see below). For the DETECT calculator, the following parameters are needed: Part I: FVC% / DLCO% (ratio), Telangiectasia (Yes/No), NT-ProBNP (pg/ml), Serum urate (mg/100ml). ECG (high axis: Yes/No). Part II: Echocardiography: Right atrial area (cm2), Tricuspid flow (TrP (m/s).

Right catheterization measures the average pressure / mean pressure (English: mean pulmonary arterial pressure) in the pulmonary artery (mPAP) or mean AP. The result is often decisive for the choice of treatment. In practice, a thin catheter is pushed through a blood vessel and down into the right part of the heart. The examination is important for distinguishing between pre-capillary and post-capillary pulmonary hypertension, which is important for choosing the right treatment. The examination calculates pulmonary wedge pressure in the left atrium (English: pulmonary "arterial" or "capillary" wedge pressure (Mean pulmonary wedge pressure PAWP or PCWP) and the resistance in the pulmonary arteries (PVR, PAR) (English: pulmonary vascular resistance). Pulmonary vascular resistance is demonstrated by precapillary PAH and indicated in Wood (≥ 2 Wood speaks for PAH). Post capillary PH is seen in left-sided heart failure where pulmonary capillary wedge pressure PCWP ≥ 15 mmHg (reference: Xanthouli P, 2020). Mixed forms can complicate the picture and are not uncommon.

  • Definition: Pulmonary Hypertension exists when the mean pressure (Medium Arterial Pressure = MAP) is above 20 mmHg at rest (revised from 25 mmHg per 2019, reference: Simonneau, 2019). MAP in trout is normally 10-20 mmHg.
  • Pre-capillary pulmonary hypertension: mean pressure (mPAP), mean AP >20 mmHg, left atrial wedge pressure (PCWP), PCV ≤ 15 mmHg, pulmonary artery resistance (PVR, PAR) ≥ 2 WU.
  • Postcapillary: AP >20 mmHg, PCWP, PCV > 15 mmHg, PVR, PAR < 2 WU.
  • Combined pre- and postcapillary: AP >20 mmHg, PAWP >15 mmHg, PVR, PAR ≥ 2WU.
  • Mild PH exists at 35mmHg (36-50mmHg with ultrasound).


Regardless of symptoms, the diagnosis is based on measurements:

  • Echo cor (ultrasound of the heart): Here calculated systolic pulmonary artery pressure indirect The measurements are less accurate than in cardiac catheter examination (see below). Estimated pressure above 30-35mmHg is suspicious of PH
  • Cardiac catheter (Right part of the heart). Mean pressure (MAP) above 20 mmHg at rest or more than 30 mmHg during exercise is pulmonary hypertension.
  • Division/classification of type/group pulmonary hypertension can be done according to definition as of 2019 by Simonneu.

Similar diseases / differential diagnoses


It is also recommended to follow recognized guidelines, such as the ESC/ERS guidelines (Humbert M, 2022).

General measures. Everyone should be vaccinated against influenza and pneumococci (pneumonia). Pregnancy should be avoided. In most cases of rheumatic disease, blood thinners (anticoagulation) are not given with warfarin (Marevan), because the increased risk of bleeding is unfavourable. In cases with Antifosfolipid syndrome however, anticoagulation must be considered against the increased risk of venous thrombosis. On-site training/rehabilitation for heart/lung disease is applicable.


Calcium channel blockers is effective in only 5-8% of patients and is only preferred for those who respond to tests during cardiac catheterization. Current calcium blockers are: amlodipine, diltiazem, felodipine and nifedipine.

Endothelin antagonists: Bosentan "Cipla" (Tracleer, Stayveer). Endothelin A+B inhibits wood NYHA class II-III. Effect on 6-min walking test, O2 uptake, delays deterioration. Long-term effect. Known security profile. Bosentan ("Accord") written on H prescription and is covered by the health enterprise. Interactions: The Marevan dose must often be increased, fluconazole (Diflucan) (anti-mycotics) significantly increases bosentan plasma levels, do not give ciclosporin (Sandimmun) or glibenclamide (for diabetes). Controls; Liver enzymes: stop treatment if 2-3 x upper reference range. Check hemoglobin. Ambrisentan (ET-A antagonist): Volibris, Endothelin A (ETA) -selective receptor antagonist, 5-10mg x1 in NYHA II-III. Side effects: Headache, edema, anemia (reactive?), Abdominal pain. Volibris is prescribed on H-prescription. Marcitentan (Opsumit) (Endotelin antagonists A+B inhibit), Opsumit is as of 2023 more expensive than Volibris, but Volibris should not be given in pulmonary fibrosis (which is often present in systemic sclerosis and PAH). Opsumit is prescribed on H-prescription. Check: Liver enzymes monthly, Hgb. Interactions: Marevan-neutral.

PD-5 Inhibitors / Nitrogen Oxides: Sildenafil (20-80mg/d): Mysildecard, Orisild 20mg x 3 / Revatio / Viagra 25mg, / At NYHA II-III. Selective inhibition of CGMP-specific phosphodiesterase type 5 (PDE5). Orisild ("Orion") is written on H-prescription and is covered by the health institution. Tadalafil (Adcirca) can be given once a day.

Priociguat, guanylate cyclase agonist. The only drug that is approved for chronic blood clots (thromboembolic syndrome) if one cannot be operated on. 

Prostacyclin analogues: Selexipag (Uptravi) tablets, selective IP agonist, individual dose titration. Prostacyclin analogues for inhalation (Iloprost, treprostinil) and for IV. or sc. administration (epoprostenol iv, treprostinil iv or sc).

Combination treatment. With NY class II, the treatment goal is that one remains in class II, improvement of the 6-minute walk test and no worsening of the CI (Cardiac index). For NY class II-III, the first choice is the endothelin I receptor antagonist bosentan with sildenafil as an alternative. If no improvement can be traced after 3 months, combination treatment is used (for example bosentan and sildenafil). Treatment goals for class III (and IV) are transition to class II, improvement of 6 MWT, normalization of CI and 30% drop in PVR (pulmonary vascular resistance). For NY class IV, one can in selected cases try epoprostenol (Flolan) in a central venous catheter, possibly combination treatment bosentan/sildenafil or bosentan/epoprostenol. One should also consider whether transplantation is appropriate. Patients in functional class IV with tachycardia > 110/min and blood pressure < 90 mm Hg should be treated in the intensive care unit.


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