PULMONARY HYPERTENSION VS HEART FAILURE:
IS THIS HEART FAILURE LEFT-SIDED OR RIGHT-SIDED?
MILTON PACKER, M.D

Pulmonary hypertension refers to a group of disorders, which are characterized by an increase in pulmonary arterial pressure. Pulmonary hypertension may result from an increase in pulmonary venous pressure, an increase in pulmonary arterial resistance, or a combination of both abnormalities.

The most common cause of pulmonary hypertension is an increase in pulmonary venous pressure, generally resulting from heart failure due to left ventricular systolic dysfunction. Such patients respond favorably to digitalis, diuretics, angiotensin converting enzyme inhibitors, beta-blockers and aldosterone antagonists. The use of these drugs can dramatically reduce pulmonary artery pressures in these patients, and thus, act as an important treatment for this form of pulmonary hypertension.

It is noteworthy that, in patients with left heart failure and increase pulmonary venous pressures, the increase in pulmonary venous pressure may trigger pulmonary arterial vasoconstriction. This vasoconstriction has long been believed to provide a protective effect in slowing the flow of blood across the lungs and into the left ventricle. The pulmonary arterial vasoconstriction acts to ameliorate loading conditions on the left side of the heart but exacerbate loading conditions on the right side of the heart. In these patients, treatment with pulmonary vasodilators may act to antagonize this protective mechanism; the resulting increase in transpulmonary blood flow may increase volume overload on the left side, worsen the symptoms of heart failure and trigger pulmonary edema. This sequence of events likely explains why the administration of acetylcholine, endothelin antagonists, prostacyclin (epoprostenol) and calcium channel antagonists (amlodipine) to patients with left ventricular systolic dysfunction has been associated with worsening heart failure, particularly during the initiation of treatment.

In contrast, some patients have pulmonary hypertension as a result of a primary pulmonary arterial disease, which may result from vasoconstriction or vascular remodeling, or both. Such patients generally have normal left ventricular function and left ventricular filling pressures, and they respond very favorably to pulmonary vasodilators, such as endothelin antagonists and prostacyclin (epoprostenol). These drugs are capable not only of antagonizing vasoconstriction, but also of interrupting and potentially reversing the abnormal pulmonary vascular remodeling, which contributes importantly to the development of pulmonary hypertension.

Interestingly, it is possible for both causes of pulmonary hypertension to coexist in the same patients. Such patients have left ventricular dysfunction that is associated with excessive degrees of pulmonary arterial vasoconstriction, i.e., they have increases in pulmonary vascular resistance that are out of proportion to those expected from an increase in pulmonary venous pressures. The clinical situation in these patients can be particularly confusing if they have left ventricular dysfunction that is associated with a preserved left ventricular ejection fraction. Such individuals present with exertional dyspnea, pulmonary hypertension and a preserved left ventricular ejection fraction, and thus, appear to have all of the principal characteristics of patients with primary pulmonary arterial disease. The fact that these patients have increased left ventricular filling pressures only becomes apparent during pulmonary arterial catheterization.

The management of patients with left heart failure and disproportionate pulmonary arterial vasoconstriction is unknown. Theoretically, partial antagonism of the disproportionate vasoconstriction may act to enhance cardiac output and decompress the right ventricle. On the other hand, more complete antagonism of the pulmonary vasoconstriction may allow for excessive filling of the left ventricle, a disproportionate increase in left ventricular filling pressures and worsening symptoms of left heart failure.

Future studies are needed to understand the role of the pulmonary arterial circuit in patients with left heart failure and disproportionate pulmonary arterial vasoconstriction. Clinical trials will define whether such patients should receive treatment with pulmonary vasodilators.