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Recommendations for PAH Associated with Connective Tissue Disease

"1.In patients with PAH associated with CTD the same treatment algorithm as in patients with IPAH is recommended. (Strong Recommendation: Grade A)"

"2. xxx. (Strong Recommendation: Grade A)"

"3. xxx. (Strong Recommendation: Grade A)"

"4. xxx. (Strong Recommendation: Grade A)"

"1. yyy. (Expert Opinion: Grade E)"

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Increase in the Mean Pulmonary Arterial Pressure

PH is defined as an elevated mean pulmonary artery pressure (PAP) as measured by right heart catheterization at rest.

Increase in the Pulmonary Vascular Resistance

Occlusion of the small pulmonary arteries and arterioles

• Idiopathic PAH
• Connective tissue disease
• HIV infection
• Congenital heart disease

Decrease in the area of the pulmonary vascular bed

• Pulmonary emboli
• Interstitial lung disease

Hypoxic vasoconstriction

• Hypoventilation syndromes
• Parenchymal lung disease

Increase in The Right-sided Cardiac Output due to Left-to-Right Shunt

• Congenital heart diseases: atrial septal defects, ventricular septal defects, patent ductus arteriosus

Increase in the Pulmonary Venous Pressure

• Mitral valve disease
• Left ventricular systolic or diastolic dysfunction
• Constrictive pericarditis
• Restrictivecardiomyopathy
• Pulmonary veno-occlusive disease

Sequence of Events in Pulmonary Hypertension

Pulmonary hypertension has several pathophysiologic mechanisms depending on the underlying etiology. Nevertheless, the following sequence of events is almost always present:

• An initiating factor leads to increased resistance in the pulmonary vasculature causing narrowing of the vessels and impaired blood flow, much as it is harder to make water flow through a narrow pipe as opposed to a wide one.

• As a consequence, the right ventricle adapts by increasing right ventricular systolic pressures to preserve the cardiac output from the right heart.

• Over time, increasing right ventricular systolic pressures will subsequently result in chronic changes in the pulmonary circulation and progressively the affected blood vessels become both stiffer and thicker, further increasing the blood pressure within the lungs and impairing blood flow.

• In addition, the increased workload of the heart causes thickening and enlargement of the right ventricle, making the heart less able to pump blood through the lungs, causing right heart failure.

• As the blood flowing through the lungs decreases, the left side of the heart receives less blood. This blood may also carry less oxygen than normal. Therefore it becomes harder and harder for the left side of the heart to pump to supply sufficient oxygen to the rest of the body, especially during physical activity.

The Role of Endothelial Cells Injury

All classes of pulmonary hypertension are associated with narrowing and obliteration of the pulmonary arterioles due to thickening of the intima by fibromuscular dysplasia. This constant finding has increased the interest in the role of endothelial injury and the release of vasoactive mediators in the pathogenesis of pulmonary hypertension. These mediators include both vasoconstrictors and vasodilators. Whereas the main vasoconstrictor is Endothelin, Nitric Oxide (NO), PGI2 and endothelium derived hyperpolarizing factor (EDHF) are vasodilators, of which NO is the most potent in reversing the effects of Endothelin.

Factors Determining the Ability of the RV to Adapt to Increased PVR

1. Age of the patient at onset.
2. Rapidity of onset of pulmonary hypertension.
3. Coexisting hypoxemia.