The Early Recognition of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a rare, life-threatening disease. It is characterised by the elevation of pulmonary arterial pressure and pulmonary vascular resistance. A remodelling of small pulmonary vessels characterised by the proliferation of the adventitia, the hypertrophy of the media and fibrosis of the intima can be observed on the microscopic level.

According to the actual classification of Venice (2003), PAH can be idiopathic, familiar or associated to other diseases and conditions (APAH). About 15 different clinical entities belong to the APAH group: connective tissue diseases such as systemic sclerosis, mixed connective tissue disease, or systemic lupus erythematodes being among the most frequent. The development of APAH in these diseases results in decreased survival. Successful therapies include prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors, however, the effects in associated conditions appear smaller compared to idiopathic PAH. The early recognition of APAH may promote better treatment results and prognosis.

Hemodynamically, PAH has been defined as a mean pulmonary arterial pressure (MPAP) > 25mmHg at rest, or > 30mmHg during exercise.

It is assumed that in the early stages of PAH, pulmonary arterial pressure values may be normal at rest, but the remodelling of small arteries leads to stiffening resulting in increased pulmonary arterial pressure during exercise (latent PAH).

Doppler echocardiography, by using the tricuspid regurgitation jet and the simplified Bernoulli-equation, is a well established clinical method for the estimation of systolic pulmonary arterial pressure at rest (rSPAP). A close correlation between rSPAP values from echo and right heart catheterisation (RHC) has been described. A promising non-invasive method to detect SPAP during exercise is Exercise Tricuspid Echo Doppler (ETED). Previous studies suggested, that SPAP during exercise can be assessed with ETED in patients with connective tissue diseases, and it was suggested that a considerable proportion of these patients suffered from latent PAH. However, the results of these studies were not controlled by the gold standard RHC. According to present guidelines, RHC is needed for the definite diagnosis of PAH, which allows the precise measurement of MPAP, pulmonary arterial wedge pressure, right atrial pressure and cardiac output, and the calculation of pulmonary vascular resistance.

Cardiopulmonary exercise testing (CPET) is a reliable method to objectively evaluate exercise capacity. Patients with latent PAH may suffer from dyspnea and early fatigue during exercise and may have a reduced exercise capacity. A low peak O2 uptake was associated with a poor prognosis in patients with PAH.

In the present study we investigate patients with risk factors for PAH by combining ETED and CPET and control the results by RHC at rest and during exercise.

Inclusion criteria

• Systemic sclerosis
• SLE
• Late corrected left-right shunt
• HIV Infection
• Splenectomy over 10 years
• Haemoglobinopathy and Thrombocytosis
• Ventriculo-atrial Shunt
• Liver cirrhosis/other portal Hypertension
• Anamnestic Aminorex or PhenFen abuse
• Close relatives of patients with IPAH
• Healthy controls

Exclusion criteria

• Known PAH
• Severe lung or bronchial disease (FEV1 <70% predicted)
• Systolic LV dysfunction (LVEF <50%) or diastolic dysfunction (pulmonary arterial "wedge" pressure (PAWP) ≥15 mmHg)
• Valvular dysfunction > Grad I (except of Tricuspidal- and Pulmonary insufficiency)
• Uncontrolled systemic arterial hypertension (rest >150 mmHg systolic or 90 mmHg diastolic; exercise >220 mmHg systolic)
• Uncontrolled ventricular arrythmia
• Uncontrolled supraventricular arrythmia
• Myocardial infarction within last 12 months
• Pulmonary embolism within last 12 months
• Significant change in therapy or larger operation within last 12 weeks
• Inability of performing exercise on cycle ergometer