11.10: Pulmonary Hypertension
- Page ID
- 42794
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Introduction
Pulmonary hypertension (PH) is a progressive life-threatening condition and associated with a high rate of mortality, despite medical intervention. PH is characterized by elevated pulmonary arterial pressure and secondary right ventricular failure.
The definition of pulmonary hypertension (PH) is based upon right heart catheterization where PH is defined as a mean pulmonary artery pressure greater than 25 mmHg at rest.
Classification
PH is classified into five groups:
- Pulmonary arterial hypertension (PAH). This group consists of idiopathic PAH and PAH due to connective tissue diseases, HIV infection, portal hypertension, congenital heart disease, schistosomiasis, chronic hemolytic anemia, persistent pulmonary hypertension of the newborn, pulmonary veno-occlusive disease, drug- and toxin-induced PH and pulmonary capillary hemangiomatosis.
- Pulmonary hypertension owing to left heart disease. PH due to systolic dysfunction, diastolic dysfunction, or valvular heart disease is included in this group.
- Pulmonary hypertension owing to lung diseases or hypoxemia. This group includes PH due to chronic obstructive pulmonary disease, interstitial lung disease, other pulmonary diseases with a mixed restrictive and obstructive pattern, sleep-disordered breathing, alveolar hypoventilation disorders, and other causes of hypoxemia [4].
- Chronic thromboembolic pulmonary hypertension. This group includes patients with PH due to thromboembolic occlusion of the proximal or distal pulmonary vasculature.
- Pulmonary hypertension with unclear multifactorial mechanisms. These patients have PH caused by hematologic disorders (eg, myeloproliferative disorders), systemic disorders (eg, sarcoidosis), metabolic disorders (eg, glycogen storage disease), or miscellaneous causes
Pulmonary arterial hypertension in congenital heart disease
In approximately 6% of adults with congenital heart disease PAH develops. In fact congenital heart disease has emerged to be one of the commonest associated causes of PAH.
The occurrence of PAH in congenital heart disease is usually the result of systemic-to-pulmonary shunting, leading to a blood volume overload of the pulmonary vasculature. Left to right shunts are most common; VSD, ASD, patent ductus arteriosus or AVSD.
Pathophysiology
The pathogenesis of PH is complex and just beginning to be elucidated. In patients with congenital heart disease, left-to-right intracardiac shunting increases flow through the pulmonary vasculature, this causes shear forces that disrupt the vascular endothelium and activate cellular mechanisms critical to the pathogenesis and progression of PAH.
The mechanism of damage to the pulmonary vasculature differs in patients with ASD compared to VSD. Vascular injury is related to the degree and duration of volume overload alone with an ASD, whereas high pressure shear forces also contribute with a VSD.
In patients with an ASD, shunting is delayed until maturation of the pulmonary vasculature occurs. The normal pulmonary vasculature is able to accommodate the increased volume of flow by vasodilating and recruiting previously unperfused vessels; thus, pulmonary artery pressures do not rise significantly in most patients with an ASD until adult life. In contrast to patients with an ASD, clinical sequelae always develop in patients with a large (nonrestrictive) VSD. Severe PAH is present from birth because of the unique hemodynamics. The combined effect of volume overload and shear forces elevates the pulmonary vascular resistance, which becomes fixed during childhood. As a result, shunt reversal (right-to-left flow) is common, with hypoxemia resulting. This is often referred to as the Eisenmenger syndrome.
Eisenmenger syndrome forms a small percentage (1%) of CHD patients and is defined as CHD with an initial large systemic-to-pulmonary shunt that induces progressive pulmonary vascular disease and PAH, with resultant reversal of the shunt and central cyanosis. Eisenmenger syndrome represents the most advanced form of PAH associated with CHD. An important subgroup in this Eisenmenger population is patients with Down syndrome.
Classification
Pulmonary arterial hypertension in congenital heart disease can be divided into four quite distinct phenotypes, which may be feasible to use in clinical practice.
A. Eisenmenger syndrome. This includes all systemic-to-pulmonary shunts resulting from large defects and leading to a severe increase in pulmonary vascular resistance (PVR) and a reversed (pulmonary-to-systemic) or bidirectional shunt; cyanosis, erythrocytosis, and multiple organ involvement are present.
B. PAH associated with systemic-to-pulmonary shunts. This includes moderate to large defects; PVR is mildly to moderately increased, systemic-to-pulmonary shunt is still prevalent, and no cyanosis is present at rest.
C. PAH associated with small defects. This includes small defects (usually VSD<1 cm and ASD <2 cm of effective diameter assessed by echocardiography).
D. PAH after corrective cardiac surgery. In this group of patients the congenital heart disease has been corrected, but PAH is still present immediately after surgery or recurs several months or years after surgery in the absence of significant postoperative residual lesions.
Treatment
Early treatment of PH is generally suggested because advanced disease may be less responsive to therapy. PAH is characterized by symptoms of dyspnea, fatigue, chest pain, and syncope. Primary therapeutic strategy should be considered in all patients with PAH and consists of diuretic, oxygen, anticoagulant, and digoxin therapy, as well as exercise and lifestyle advices.
Injured endothelial cells release factors that are known to contribute to PAH. Inhibition of these factors forms the basis of some of the advanced therapies for PAH. Patients with CHD-PAH who progress to NYHA functional class II, III, or IV, qualify for advanced therapy. This is irrespective of any primary therapy given.
Advanced therapy is directed at the PAH itself, rather than the underlying cause of the PAH. For PAH treatments with advanced therapy three main pathways have been detected: prostacyclin, nitric oxide and endothelin-1.This resulted in therapies with prostanoids such as epoprostenol, phosphodiesterase-5 inhibitors such as sildenafil and endothelin-1 receptor antagonists such as bosentan.
Outcome
The prognosis is generally poor but varies according to the severity of the underlying cause, the functional abnormalities, and the hemodynamic abnormalities. Factors that may indicate a poor prognosis include age at presentation greater than 45 years, NYHA functional class III or IV, failure to improve to a lower NYHA functional class during treatment, pericardial effusion, large right atrial size, elevated right atrial pressure, septal shift during diastole, decreased pulmonary arterial capacitance (ie, the stroke volume divided by the pulmonary arterial pulse pressure) and increased N-terminal brain natriuretic peptide level.
Therapy improves exercise capacity and functional class, however the impact on mortality has been less well established.