Etiology and Pathogenesis

Pulmonary artery pressure (PAP), the pressure that must be sustained by the right ventricle, is equal to pulmonary flow (PF) times pulmonary vascular resistance (PVR) plus pulmonary venous pressure (PVP) [PAP = (PF × PVR) + PVP]. Normal PAP in systole is 18 to 25 mm Hg, and mean PAP is 12 to 16 mm Hg. The normal PVP is approximately 6 to 10 mm Hg, giving a total pressure gradient that averages approximately 5 mm Hg.

A complicated array of physiologic and pathologic responses to perturbations of any of these variables will cause changes in the others. For this reason, the underlying cause of end-stage pulmonary hypertension in an individual patient may be difficult to determine. For instance, chronically elevated pulmonary flow caused by systemic arterial-venous shunting will lead to increased PVR that requires concomitantly greater increases in PAP for maintenance of blood flow. In another example, chronically elevated left atrial pressures due to mitral stenosis create a requirement for increased PAP. However, over time, PVR increases in patients with mitral stenosis by yet unknown mechanisms and can lead to persistent pulmonary artery hypertension even after the mitral stenosis is relieved.

Pulmonary artery hypertension can therefore be secondary to many diseases. Some of these can be treated with the reversal or slowing of pulmonary artery hypertension progression. Additionally, an important minority of patients has pulmonary artery hypertension as a primary disease with no identifiable cause. Therefore, in approaching the patient presenting with pulmonary artery hypertension, the optimal approach is to characterize pulmonary hemodynamics and use the data obtained to aggressively search for treatable underlying causes and for manageable elements of the pathophysiology. Critical in this responsibility is to recognize and address pulmonary artery hypertension as early as possible.

An expert committee of the World Health Organization has created a comprehensive diagnostic classification of pulmonary hypertension (Box 64-1). Of the many potential causes of pulmonary hypertension, the World Health Organization classification group 1—which includes idiopathic pulmonary artery hypertension (IPAH) and familial pulmonary artery hypertension (FPAH), diseases formerly referred to as “primary pulmonary hypertension”—merits special consideration. These diseases, characterized by proliferative and necrotic obliteration of the pulmonary microvasculature, are clinically indistinguishable except for family history. Both are devastating, despite advances in our understanding of their causes and treatment. Unlike the situation for many other causes of pulmonary hypertension, there are no reversible structural factors that can be addressed for individuals with IPAH and FPAH.

Clinical Presentation

Symptoms of pulmonary hypertension are common to multiple etiologies. Most patients with mild or moderate pulmonary hypertension are asymptomatic. Initial symptoms may be dyspnea with exertion, fatigue, and exertional intolerance. Many patients experience chest pain. Syncope suggests severe pulmonary hypertension with marked limitation of flow reserve. Hemoptysis is not common, but in some patients it is serious and fatal. Clinical presentation depends in part on the chronicity of the process. Adaptive changes in the right ventricle allow patients with chronic pulmonary hypertension to sustain near-systemic levels of pressures with minimal symptomatic effects. However, acute increases in pulmonary pressure, as with massive PE, cause immediate overt distress and, in many cases, collapse and death (Fig. 64-1).

Figure 64-1 Massive pulmonary embolization.

RPA, right pulmonary artery.

Two keys to the diagnosis of pulmonary hypertension are a high degree of suspicion raised by the clinical history and physical findings that suggest right ventricular (RV) failure and systemic congestion (see also Chapter 1). Increased PAPs are reflected in elevated RV systolic and, later, diastolic pressures. Because of chronically elevated RV systolic and diastolic pressure, the geometry of the right ventricle is altered, usually sufficiently to render the tricuspid valve incompetent. Tricuspid regurgitation creates a prominent v wave in the jugular venous pulse. Generally, the jugular venous pressure will be increased substantially in these patients, with filling of the deep neck veins above the clavicle visible with the patient sitting upright. Significant tricuspid regurgitation can also often be appreciated as pulsation of the liver. Less common and subtler physical findings with pulmonary hypertension are an RV precordial heave, an RV third heart sound, and increased intensity of the pulmonic component of the second heart sound.

Differential Diagnosis

Among numerous causes of pulmonary hypertension, the most common are chronic left ventricular dysfunction with or without valve disease and chronic lung diseases (see Box 64-1). These are usually recognized by history, and treatment is focused on the primary disease. All potential causes of secondary pulmonary hypertension should be excluded before a diagnosis of IPAH or FPAH is considered.

Diagnostic Approach

Table 64-1 lists the diagnostic tests and potential findings in the evaluation of patients with suspected pulmonary hypertension. Critical information on the degree and possible cause of pulmonary hypertension can be gained from a transthoracic echocardiogram. PAP can be estimated from the Doppler-derived velocity of tricuspid regurgitation and from the degree of RV dilation and hypertrophy. Echocardiography also provides data on left ventricular function, mitral valve structure and function, and the existence of an intracardiac shunt, all clues to the possibility that the pulmonary hypertension is an effect of cardiac disease.

Table 64-1 Evaluation of Patients with Suspected Pulmonary Hypertension

Information about primary pulmonary disease must also be pursued as a potential cause for pulmonary hypertension. Pulmonary function testing provides information on parenchymal and functional lung diseases. Ventilation/perfusion (V/Q) scans are useful in excluding chronic PE as the underlying etiology for pulmonary hypertension. The need to document thromboembolism is so critical to treatment and survival that pulmonary angiography must be considered for every patient with otherwise undiagnosed pulmonary hypertension. However, particularly in patients with severe pulmonary hypertension, pulmonary angiography presents an increased risk of morbidity and death. For this reason, pulmonary angiography in this setting should be performed in a center and by an operator with experience in dealing with these patients.

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