Acute vasodilator testing: An opportunity to advance the precision care of pulmonary hypertension

Abstract

The pulmonary arterial pressure of a child with severe pulmonary arterial hypertension immediately normalized while breathing nitric oxide during heart catheterization at 8 years of age. Her acute pulmonary vascular response to nitric oxide has persisted throughout her life. Her acute response to other medications has been similar to her long-term response to medications in the same class. Acute vasodilator testing with inhaled nitric oxide and other medications may be an opportunity to refine study design and advance precision care for patients with pulmonary hypertension.

Keywords: Calcium channel blocker; Guanylate cyclase; Nitric oxide; Nitric oxide synthase; Pulmonary hypertension; Vasodilator testing; calcium channel blocker(s), CCB; inhaled nitric oxide, iNO; mean pulmonary arterial pressure, mPAP; parts per million, ppm.

Fig. 1

Intensity of the second heart sound and mean pulmonary arterial pressure during acute vasodilator testing. The intensity of the second heart sound was measured during heart catheterization at an age of 14 years by acoustic cardiography. The intensity of the second heart sound changed immediately in accordance with changes in pulmonary arterial pressure during 10- to 15-min intervals of acute vasodilator testing with inhaled nitric oxide while breathing air or supplemental oxygen. L/min: liters per minute, mV: millivolts, ppm: parts per million.

Fig. 2

Effect of phosphodiesterase V inhibitors on the pulmonary vasodilatory effect of inhaled nitric oxide. The patient was monitored in the intensive care unit following heart catheterization at an age of 10 years. Pulmonary and systemic arterial pressures were measured continuously and recorded every 5 minutes for the graph. Adult doses of sildenafil (25 mg, 0.5 mg/kg) and tadalafil (5 mg, 0.1 mg/kg) were given while the patient was awake. Inhaled nitric oxide (20 parts per million) was administered for intervals of approximately 10 minutes. The pulmonary vasodilatory effect of inhaled nitric oxide was not appreciably prolonged by oral treatment with sildenafil or tadalafil. Less variability in her baseline pulmonary and systemic arterial pressures occurred while she was sleeping, between time points 8–14 hours.

Fig. 3

Timeline of acute vasodilator testing with supplemental oxygen and 20 parts per million inhaled nitric oxide and long-term outpatient therapy. The baseline ratio of pulmonary to systemic vascular resistance increased while being treated with sildenafil (25 mg/day to 75 mg/day, 0.7 mg/kg/day to 1.9 mg/kg/day) and intermittent transdermal nitroglycerin (0.2 mg/hour). A decrease in the baseline ratio of pulmonary to systemic vascular resistance occurred while being treated with amlodipine (5 mg/day to 15 mg/day, 0.11 mg/kg/day to 0.23 mg/kg/day). The ratio of pulmonary vascular resistance to systemic vascular resistance transiently increased at the onset of puberty. The effect of long-term treatment with amlodipine has not decreased the ratio of pulmonary vascular resistance to systemic vascular resistance to a level that can readily be achieved while breathing nitric oxide.