pulmonary vasodilators can worsen group 2 PH

This patient has PH from chronic hypoxemic respiratory failure (group 3) and left heart disease (group 2). The current diagnostic criterion for PH is mean pulmonary arterial pressure of >20 mm Hg and pulmonary vascular resistance (PVR) of >2 Wood units. Pulmonary capillary wedge pressure (PCWP) distinguishes between preand postcapillary PH, with PCWP <15 mm Hg being consistent with a precapillary component of PH and PCWP >15 mm Hg being consistent with postcapillary PH. Transpulmonary gradient (ie, mean PAP – mean PCWP) >12 mm Hg suggests that both preand postcapillary PH are present. Under normal physiologic conditions, the pulmonary vascular system is highly compliant with low resistance. This allows the RV to generate adequate stroke volume with one-sixth the pressure of the LV. Increased RV afterload from increased PVR requires an increase in RV systolic pressure to maintain adequate stroke volume.

In the setting of right heart failure from PH, interventions to reduce RV afterload can be helpful but should be guided by the underlying etiology of PH, namely increased left atrial pressure, increased PVR, or increased cardiac output. In postcapillary PH, treatment with pulmonary vasodilators may have a deleterious impact on right-sided heart function as they may result in increased left-sided filling and may increase left atrial and LV end-diastolic pressure. In the setting of conditions such as pulmonary vein stenosis, mitral valvular stenosis, and LV systolic or diastolic dysfunction, increased blood flow from pulmonary vasodilation can lead to increased left-sided filling pressure and subsequent hydrostatic pulmonary edema. In the clinical scenario of this question, inhaled nitric oxide may decrease RV afterload and improve RV stroke volume but can put a left ventricle with systolic dysfunction at a preload disadvantage, leading to elevated PCWP and hydrostatic edema. Inhaled nitric oxide does not have direct effects on systemic vascular resistance.

Historically, pulmonary vasodilators have been viewed as potentially detrimental in group 3 PH because of the potential to increase perfusion to poorly ventilated areas of the lung and worsen V/Q mismatch. However, clinical studies have suggested that inhaled pulmonary vasodilators are preferentially delivered to well-ventilated areas of the lung and can therefore increase perfusion to those areas, improving oxygenation. A randomized controlled trial of inhaled treprostinil demonstrated improvement in the 6-min walk test and modest decrease in clinical worsening compared with the placebo group. Studies of endothelin receptor antagonists (ARTEMIS) and riociguat (RISE-IIP) have not demonstrated clinical improvement in group 3 PH, and some have had a signal of harm, and studies of phosphodiesterase type 5 inhibitors have had mixed results.12345678

Footnotes

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