How can the progression of secondary pulmonary hypertension be delayed in severe heart failure?

Severe heart failure often triggers reactive pulmonary hypertension (PH), which then constitutes an independent predictor of morbidity and mortality. The pulmonary circulation is a low-pressure, high-capacity system. At sea level, the normal pulmonary artery systolic pressure is $25 mm Hg. Conventionally, PH is defined as a mean pulmonary artery pressure of 25 mm Hg at rest or 30 mm Hg during exercise. PH may be due to increased left atrial pressure (measured as pulmonary capillary wedge pressure [PCWP]), and/or increased resistance in the pulmonary arterial tree.

In the early phase of chronic cardiac decompensation, PCWP increases due to the increase in left ventricular filling pressure and/or mitral regurgitation. At this stage, PH is a direct response to left ventricular dysfunction and can be reversed by increasing therapy with vasodilators (angiotensin-converting enzyme [ACE] inhibitors) and diuretics, since arterial resistances are not increased.

Later, however, dysregulation of vascular smooth muscle tone and structural remodeling of arterial wall occur, eventually resulting in abnormal elastic fibers, intimal fibrosis, and medial hypertrophy. Vascular stiffness depresses vasodilator responsiveness. The hemodynamic consequence is an increase in the difference between mean arterial pulmonary pressure and PCWP, signifying increased vascular resistance. This model of PH is only reversible by vasodilators in the initial functional stage. Once anatomical abnormalities occur in the arterial wall, however, PH becomes fixed, irreversible, and only sluggishly responsive to drug intervention. Hemodynamic mechanisms such as pressure and volume overload, together with endothelial dysfunction (decreased production of endothelium-derived nitric oxide [NO] and increased production of vasoconstrictors such as endothelin [ET-1]), play an important role in the pathogenesis of secondary PH.

There is no specific treatment for PH in heart failure, but treatment of the heart failure succeeds to some extent in limiting the underlying structural changes in the pulmonary capillaries and arterioles. Although continuous prostacyclin infusion is effective in primary PH, it is ineffective in PH associated with severe heart failure. Similarly, although endothelin receptor blockers and specific phosphodiesterase inhibitors have proved effective in primary PH, there are no data available for heart failure patients with secondary PH.

Oral anticoagulant therapy is useful for slowing the progression of pulmonary artery lesions and lowering the risk of thrombosis in the pulmonary circulation. It is indicated in all patients with PH: prospective and retrospective studies have shown that it decreases mortality. The dosage is adjusted to maintain the international normalized ratio (INR) between 2 and 3.

The assessment of PH is pivotal in setting the indications for heart transplantation in patients with severe heart failure. A fixed gradient >15 mm Hg between mean arterial pulmonary pressure and PCWP contraindicates transplantation as the grafted right ventricle will be unable to sustain the increased pulmonary pressure. Pharmacological methods may help to test the reversibility of pulmonary vascular resistance. Enoximone (or milrinone), a phosphodiesterase inhibitor, has vasodilator and inotropic properties: infusion can be used to detect a subgroup of responders showing an acute decrease in pulmonary resistance. Nitrate and prostacyclin infusions are used for the same purpose.

Kkywords

symptom; diagnosis; secondary pulmonary hypertension; pathophysiology; hypertension; hemodynamics; treatment

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