CLASSIFICATION AND PATHOPHYSIOLOGY

Modified from Simonneau G, Galie N, Rubin LJ, et al: Clinical classification of pulmonary hypertension. J Am Coll Cardiol 43:5S-12S, 2004. ASD, atrial septal defect; HIV, human immunodeficiency virus; PDA, patent ductus arteriosus; VSD, ventricular septal defect; COPD, chronic obstructive pulmonary disease.

Pathophysiology

In clinical practice, pulmonary arterial pressure is commonly assumed to be reflective of pulmonary vascular resistance, and in most circumstances this is the case. However, based on Equation 1-6, it is clear that pulmonary arterial pressure is also dependent on cardiac output and left atrial pressure. An increase in cardiac output can lead to an increase in pulmonary arterial pressure despite a fall in pulmonary vascular resistance. Conversely, an acute rise in pulmonary vascular resistance resulting in acute right ventricular failure and thus a fall in cardiac output may cause a fall in pulmonary arterial pressure.

Under normal circumstances, as cardiac output increases in response to increased metabolic demands, pulmonary vascular resistance falls due to distension and recruitment of pulmonary capillaries; thus, pulmonary arterial pressure is relatively unchanged. With elevated pulmonary vascular resistance, this normal response of the pulmonary vascular bed is lost, and pulmonary arterial pressure rises as cardiac output increases. Over time, as pulmonary vascular disease progresses, the ability of the right heart to increase its output is reduced and cardiac output becomes relatively fixed. Eventually, right ventricular failure develops and cardiac output is reduced even under resting conditions.

The extent to which the right ventricle can cope with increased pulmonary vascular resistance depends on the time period over which the increased resistance has occurred. An untrained, thin-walled right ventricle is sensitive to acute rises in afterload. Thus, an abrupt rise in pulmonary vascular resistance (e.g., due to a massive pulmonary embolism) that requires a mean pulmonary arterial pressure of more than 40 mmHg to perfuse the pulmonary bed will rapidly lead to right ventricular failure. In contrast, if pulmonary vascular resistance increases gradually, right ventricular hypertrophy develops, which allows resting cardiac output to be maintained in the face of very high pulmonary vascular resistance (e.g., >20 Wood units). In this situation, pulmonary arterial pressure may approach or even exceed systemic arterial pressure.

With raised left atrial pressure, increased pulmonary arterial pressure can occur without raised pulmonary vascular resistance (see Equation 1-6). This is termed passive pulmonary hypertension. In passive pulmonary hypertension, the increase in pulmonary arterial pressure is usually mild and the transpulmonary gradient (see Chapter 1) is normal. The common causes of passive pulmonary hypertension are mitral valve disease and left ventricular dysfunction. The term active pulmonary hypertension denotes pulmonary hypertension due to vasoconstriction or anatomic restriction within the pulmonary bed in association with normal left atrial pressure. Pulmonary vascular resistance and transpulmonary gradient are elevated. Causes of active pulmonary hypertension include chronic lung disease and chronically elevated flow through the pulmonary circulation, such as that which occurs with uncorrected systemic-to-pulmonary shunts. The term reactive pulmonary hypertension refers to active pulmonary hypertension due to long-standing passive pulmonary hypertension. Chronically elevated left atrial pressure eventually causes pathologic changes within the pulmonary arterioles. The most common cause of reactive pulmonary hypertension in cardiac surgery patients is chronic mitral valve disease, particularly mitral stenosis. Rarely, left ventricular failure leads to reactive pulmonary hypertension. Pulmonary hypertension may be severe.

Pulmonary hypertension may be fixed or responsive. Changes in the pulmonary vascular bed that accompany active or reactive pulmonary hypertension include vasoconstriction, endothelial and smooth muscle proliferation, thrombosis, and fibrosis. Pulmonary hypertension that is associated with extensive thrombosis, fibrosis, or tissue destruction tends to be fixed, whereas pulmonary hypertension that is associated with abnormal vasoconstriction may be responsive to pulmonary vasodilating agents. Impaired production of vasodilator substances, such as nitric oxide, prostacyclin, and vasoactive intestinal peptide, and increased production of vasoconstrictor substances, such as endothelin-1 and thromboxane-A2, have been identified for a range of conditions associated with pulmonary hypertension.¹ Alveolar hypoxemia is a potent stimulus for pulmonary vasoconstriction, and it contributes to pulmonary hypertension in patients with chronic lung disease.

DIAGNOSIS

The symptoms of secondary pulmonary hypertension are determined primarily by the underlying cardiac or respiratory pathology. Symptoms attributable to pulmonary hypertension per se relate to the relatively fixed cardiac output. These symptoms include dyspnea on exertion, dizziness, syncope, palpitations, and fatigue. Physical findings of pulmonary hypertension are those of right ventricular pressure overload, and are not usually apparent unless systolic pulmonary arterial pressure exceeds 50 mmHg. Physical findings include a right ventricular heave, a loud pulmonary component of the second heart sound (P₂), a large A wave on the jugular venous trace, a pulmonary ejection click, and a pulmonary flow murmur. Symptoms and signs of right ventricular failure may be present (see subsequent material).

With severe pulmonary hypertension, the electrocardiogram (ECG) typically demonstrates right ventricular hypertrophy and right axis deviation (Fig. 24-1). On the chest radiograph, characteristic features of pulmonary hypertension include enlargement of the main and central hilar pulmonary arteries (Fig. 24-2) and reduced vascular markings in the peripheries (pruning of the vessels). Signs of left ventricular dysfunction or lung disease may be evident.

Figure 24.1 An electrocardiogram in a patient with severe pulmonary hypertension. Right axis deviation (predominant S wave in lead I) and right atrial enlargement (peaked P wave in lead II; height, ≥2.5 mm) are present. A dominant R wave is seen in lead V1, and there is poor R wave progression. T wave inversion is present in leads V1 through V5, consistent with right ventricular strain.

Figure 24.2 Chest radiograph in a patient with severe pulmonary hypertension secondary to an atrial septal defect. There is enlargement of the main and central hilar pulmonary arteries (PA) and reduced vascular markings in the lung field peripheries. The central strut of an atrial septal defect closure device is seen (arrow).