Primary Pulmonary Hypertension (PPH) is a progressive
disease characterized by raised pulmonary vascular resistance, which results
in impaired right-heart function as a consequence of the increased right
ventricular afterload and occurring in the absence of an identifiable cause.
Idiopathic Pulmonary Hypertension (IPAH); pulmonary hypertension
(PHT). It is also termed precapillary pulmonary hypertension.
First described clinically and hemodynamically in 1951 by D.T.
Dresdale and colleagues.
Approximately 1-3:1,000,000 population per year in the United States and
Autosomal dominant inheritance with incomplete
penetrance and a 2.5:1 female predilection. The PPH1 gene was mapped to
chromosome 2q31-q32. A worsening of the disease occurs in successive
Current theories on pathogenesis focus on
abnormalities in interaction between endothelial and smooth-muscle cells.
Endothelial-cell injury may result in an imbalance in endothelium-derived
mediators, favoring vasoconstriction. Defects in ion-channel activity in
smooth-muscle cells in the pulmonary artery may contribute to
vasoconstriction and vascular proliferation. Inflammatory oxidant mechanisms
and deficiency in nitric oxide (NO) have also been implicated in the
pathogenesis of pulmonary hypertension. In addition, the findings of
frequent monoclonal endothelial cell proliferation in PPH also suggest that
a somatic genetic alteration similar to that present in neoplastic processes
might be responsible for the pathogenesis of PPH.
On chest radiography, the width of the pulmonary
arteries is increased and the peripheral lung fields are clear. The electrocardiogram
demonstrates right ventricular hypertrophy, as does echocardiography.
Cardiac catheterization with measurement of pulmonary artery pressures
demonstrates elevation of systolic pulmonary artery pressure >35 mmHg or
mean pulmonary artery pressure >25 mmHg. Histology shows extension of muscle
layers into small pulmonary arteries that are normally nonmuscular. The
cross-sectional area of the pulmonary vascular bed is also decreased.
Histopathology shows plexiform lesions composed of proliferating endothelial
cells present in 20 to 80% of cases of primary pulmonary hypertension.
Other diagnostic testing primarily excludes secondary causes.
Neonatal pulmonary hypertension results in
right-to-left shunting via the foramen ovale, or ductus arteriosus, or both.
Right-heart failure is inevitably present. It is usually lethal. In older
children or adults, the predominant symptoms include exertional dyspnea and
fatigue, which result from fixed cardiac output in response to exertion. PPH
occurs most commonly in young and middle-age women; mean survival from onset
of symptoms is 2 to 3 years. Primary pulmonary hypertension is progressive,
and there is no specific treatment. The terminal event may be related to
right-heart failure and is often sudden, possibly related to arrhythmias.
Catheterization is necessary to
assess hemodynamics and to evaluate vasoreactivity during acute drug
challenge. Decrease in pulmonary vascular resistance in response to acute
vasodilator challenge (intravenous epoprostenol or inhaled NO) occurs in
approximately 30% of patients, and predicts a good response to chronic
therapy with oral calcium-channel blockers (nifedipine, diltiazem,
amlodipine). Determination of the presence of cor pulmonale. Prophylaxis of
The principal consideration is to