Guidelines on diagnosis and treatment of pulmonary arterial hypertension

Definitions Body_ID: PUP20050725A002 Pulmonary hypertension (PH) is a pathophysiologic condition characterized by a mean pulmonary artery pressure (PAP) > 25 mmHg at rest or > 30 mmHg with exercise.1 Current clinical classification of PH emerging from the recently developed guidelines1 are presented in Table 1 2; clinical conditions are classified in five categories according to similar pathologic, pathophysiologic and therapeutic characteristics. Despite possible comparable elevations of pulmonary vascular resistance in the different clinical classes, the underlying mechanisms, the diagnostic approaches and the prognostic and therapeutic implications are completely different, as described in a recent journal supplement.2 Body_ID: PUP20050725A038 Figure 1 Body_ID: BUP20050725001 Body_ID: PUP20050725A034 Body_ID: PUP20050725A003 Mechanisms Body_ID: PUP20050725A004 Pulmonary arterial hypertension (PAH) is the first class (Table 1, Class 1) and is constituted by a group of rare diseases characterized by a progressive increase of pulmonary vascular resistance leading to right ventricular failure and premature death. PAH includes idiopathic PAH (Primary Pulmonary Hypertension) and PH associated with various conditions such as connective tissue diseases (CTD), congenital systemic-to-pulmonary shunts, portal hypertension and HIV infection.2 All of these conditions share equivalent obstructive pathologic changes of the pulmonary microcirculation including medial hypertrophy, intimal thickening and complex lesions (plexiform lesions, colander lesions, arteritis) of the arterioles.1 Although pulmonary vasoconstriction and endothelial dysfunction have been demonstrated in affected individuals3, the initiating pathobiologic mechanisms involved in the disease spectrum of PAH remain unknown. Endothelial dysfunction may lead to chronically impaired production of vasodilator and antimitotic substances, such as nitric oxide and prostacyclin along with over-expression of vasoconstrictors and mitogenic molecules such as thromboxane A2 and endothelin-1.3 The imbalance between these factors may initiate and perpetuate interacting processes such as vasoconstriction, proliferation, thrombosis and inflammation in the lung microcirculation. These mechanisms may be responsible for the initiation and progression of pathologic obstructive changes leading to an increased right ventricular after-load and eventually to right ventricular failure and death. Body_ID: PUP20050725A005 Diagnosis of Pulmonary Arterial Hypertension Body_ID: PUP20050725A006 The diagnostic approach to PAH requires a series of investigations aimed to confirm the clinical suspicion of PH, to clarify the clinical class and the specific underlying condition (Table 1) and to evaluate the functional and hemodynamic impairment.4,5 A sequential stage-by-stage approach can be adopted (Figure 1). Body_ID: PUP20050725A039 Figure 2 Body_ID: BUP20050725002 Body_ID: PUP20050725A035 Body_ID: PUP20050725A007 The clinical suspicion of PH should arise in any case of compatible symptoms such as dyspnea, fatigue, weakness, angina, syncope and abdominal distension (Figure 1). Symptoms at rest are reported only in very advanced cases. PH can be identified also in asymptomatic patients who undergo screening programs because of the presence of conditions that may be associated with PAH such as CTD, portal hypertension, HIV infection and congenital heart diseases. Finally, PH can be suspected in patients with incidental abnormal electrocardiographic, chest radiographic or echocardiographic findings. Body_ID: PUP20050725A008 The initial physical signs of PH include a left parasternal lift, an accentuated pulmonary component of second sound, a pansystolic murmur of tricuspid regurgitation, a diastolic murmur of pulmonary insufficiency and right ventricular third sound. Jugular vein distension, hepatomegaly, peripheral edema, ascites and cool extr...