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Effects of Phosphodiesterase Type 5 Inhibition on Systemic and Pulmonary Hemodynamics and Ventricular Function in Patients With Severe Symptomatic Aortic Stenosis
Study Questions:
What is the safety and the acute hemodynamic response to a single oral dose of sildenafil among patients with severe symptomatic aortic stenosis?
Methods:
A cohort of 20 subjects with severe symptomatic aortic stenosis (mean aortic valve area 0.7 ± 0.2 cm2; ejection fraction 60 ± 14%) received a single oral dose of sildenafil (40 or 80 mg). Other vasoactive medications were withheld, and hemodynamic data were acquired using left and right heart catheterization.
Results:
Compared with baseline, after 60 minutes, sildenafil reduced systemic (–12%; p < 0.001) and pulmonary (–29%; p = 0.002) vascular resistance, mean pulmonary artery (–25%; p < 0.001) and wedge (–17%; p < 0.001) pressures, and increased systemic (13%; p < 0.001) and pulmonary (45%; p < 0.001) vascular compliance and stroke volume index (8%; p = 0.01). These changes were not dose dependent. Sildenafil caused a modest decrease in mean systemic arterial pressure (–11%; p < 0.001), but was well tolerated with no episodes of symptomatic hypotension.
Conclusions:
This study shows for the first time that a single dose of sildenafil, a phosphodiesterase type 5 inhibitor, is safe and well tolerated in patients with severe aortic stenosis and is associated with improvements in pulmonary and systemic hemodynamics, resulting in biventricular unloading. These findings support the need for longer-term studies to evaluate the role of phosphodiesterase type 5 inhibition as adjunctive medical therapy in patients with aortic stenosis.
Perspective:
This elegant study demonstrates that, at least for the supine patient in whom other vasoactive medications were withdrawn, administration of the vasodilator sildenafil appeared to be well tolerated in the short term. The accompanying acute hemodynamic changes––with increased stroke volume presumably compensating for decreased systemic vascular resistance despite the presence of severe fixed resistance at the level of the aortic valve––counters dogma that peripheral vasodilation results in systemic hypotension among patients with severe aortic stenosis. Although this short-term hemodynamic study is not enough to assure the safety of sildenafil or prove any beneficial clinical effects associated with its long-term use, it is provocative and raises interest in a larger, longer-term study.
Keywords: Vasodilation, Oxylipins, Phosphodiesterase 5 Inhibitors, Purines, Arterial Pressure, Cardiac Catheterization, Hypotension, Piperazines, Sulfones, Pulmonary Artery, Vasodilator Agents, Hemodynamics, Heart Diseases, Cyclopentanes, Heart Failure, Stroke Volume, Ventricular Function, Vascular Resistance
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