Pulmonary hypertension (PH) is a rare lung disorder. Patients are severely ill with a life expectancy of few years after the first symptoms have occurred.
Pulmonary arterial hypertension (PH) is characterized by an abnormal elevation of the pulmonary artery pressure, the arteries that carry blood from the heart to the lungs. The arteries become narrowed and lead to a progressive increase of pulmonary vascular resistance, making it difficult for blood to flow through the vessels. As a result, right ventricle increase the systolic pressure and the blood pressure in pulmonary arteries rises far above normal levels. PH is defined by a mean > 25 mmHg at rest and 30 mmHg during exercise (normal pressure at rest is 10-20 mmHg). This abnormally high pressure strains the right ventricle of the heart, causing it to expand in size in order to improve the ventricular pumping force. Overworked and enlarged, the right ventricle gradually becomes weaker and loose its ability to pump enough blood to the lungs. The condition leads to premature death.
Despite improvements in the diagnosis and management of PH over the past 2 decades with the introduction of targeted medical therapies leading to improved survival, the disease continues to have a poor long-term prognosis.
Diagnose PH is often asymptomatic in the beginning and is typically diagnosed late in its course. The predominant symptom is dyspnea which can have an insidious onset. Shortness of breath is seen with everyday activities, such as climbing stairs and simple house hold activities. Fatigue, dizziness, and fainting spells may also be symptoms.
Swelling in the ankles, abdomen or legs, bluish lips and skin, and chest pain may occur as strain on the heart increases (cor pulmonale). Symptoms range in severity and a given patient may not have all of the symptoms.
In more advanced stages of the disease, even minimal activity will produce some of the symptoms. Additional symptoms include irregular heartbeat (palpitations or strong, throbbing sensation), racing pulse, passing out or dizziness, progressive shortness of breath during exercise or activity, and difficulty breathing at rest. Eventually, it may become difficult to carry out any activities as the disease worsens.
A thorough diagnostic evaluation of all potential causes of PAH should be undertaken. Physical examination typically reveal increased jugular venous pressure and changes in the heart sounds. Chest X/ray shows enlarged pulmonary arteries. ECG and echocardiogram show enlarged right ventricle. Functional tests as 6 minute walking distance is shorten and perfusions/ventricular diffusion capacity is always abnormal in thromboembolic Group IV PAH.
Cardiac catheterization is mandatory for accurate measurement of pulmonary artery pressure, cardiac output and left ventricular filling pressure. Very often, a left side cardiac catheterization is performed simultaneously. A short acting vasodilator is given during the catheterization to determine the extent of pulmonary vasodilator reactivity.
Pulmonary hypertension is classified in five different groups, in brief;
Group I includes disorders in which the PAH is associated with abnormalities in the small branches of the pulmonary artery, the arterioles, idiopathic PAH (IPAH) and include several types of infection, connective disorders, and some types of congenital disorders.
Group II includes PAH due to left-sided heart failure such as cardiomyopathy, diastolic dysfunction, mitral stenosis, mitral regurgitation, aortic stenosis and aortic regurgitation.
Group III includes PAH due to lung problems,
Group IV includes PAH due to pulmonary embolus or pulmonary thrombosis and
Group V includes PAH who do not fit into one of the other groups. All groups have a number of subgroups referring to specific etiological characteristics.
Group I and IV have the shortest expected lifetime. They are rare conditions and Orphan Drug Designation for SER100 PH Group I and IV may be possible.
Adult females are almost three times as likely to present with PH as adult males. The presentation of PH within children is more evenly split along gender lines and may thus be a special group and separate Orphan Designation for this patient population will be discussed with advisors and regulatory authorities.