Nitroprusside in Low-Gradient Severe Aortic Stenosis With Preserved EF

Study Questions:

What is the hemodynamic response to sodium nitroprusside among patients with low-gradient (LG) severe aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF)?


Symptomatic patients with LG severe AS (echo/Doppler aortic valve area [AVA] <1.0 cm2 or AVA index <0.6 cm2/m2, and mean gradient <40 mm Hg) and preserved EF (≥50%) who underwent clinically indicated cardiac catheterization were studied, with comparison of hemodynamic measurements before and after nitroprusside. Patients were excluded if baseline systolic blood pressure was <100 mm Hg or mean arterial pressure <60 mm Hg. Nitroprusside was initiated at a dose of 0.5 mcg/min/kg, and increased at 0.5-1.0 mcg/min/kg every 5 minutes until one of several predefined endpoints was reached: maximal dose of 10 mcg/kg/min; AV mean gradient >40 mm Hg; mean aortic pressure (MAP) <60 mm Hg; or development of intolerable patient side effects and/or symptoms. Effective arterial elastance (Ea) was calculated as the ratio of LV end-systolic pressure to stroke volume index (SVI); total systemic arterial compliance (Ca) was calculated as the ratio of SVI to aortic pulse pressure; systemic vascular resistance index was calculated as the difference between MAP and mean right atrial pressure relative to the corresponding cardiac output; and valvuloarterial impedance (Zva) was calculated as the ratio of the sum of aortic systolic pressure and transvalvular gradient to SVI. Low-flow (LF) was defined as SVI ≤35 ml/m2.


Forty-one subjects (25 LF, 16 normal flow [NF]) were included. At baseline, LF patients had lower total arterial compliance (0.36 ± 0.12 vs. 0.48 ± 0.16 ml/m2/mm Hg, p = 0.01) and greater Ea (2.77 ± 0.84 vs. 1.89 ± 0.82 mm Hg · m2/ml, p = 0.002). In all patients, nitroprusside reduced elastance, LV filling pressures, and pulmonary artery pressures; and improved compliance (p < 0.05). AVA increased to ≥1.0 cm2 in 6 LF (24%) and 4 NF (25%) subjects. Change in SVI with nitroprusside varied inversely to baseline SVI, and improved only among patients with LF LG severe AS (3 ± 6 ml/m2, p = 0.02).


Nitroprusside reduces afterload and LV filling pressures in patients with LG severe AS and preserved EF, enabling reclassification to moderate stenosis in approximately 25% of patients. An inverse relationship between baseline SVI and change in SVI with afterload reduction was observed, suggesting that heightened sensitivity to afterload is a significant contributor to LF LG severe AS pathophysiology. These data highlight the utility of afterload reduction in the diagnostic assessment of LG severe AS.


LG severe AS with preserved LVEF is a heterogeneous and incompletely understood condition; contributed to by variability in flow (normal flow [SVI >35 ml/m2] vs. LF [SVI ≤35 ml/m2]), and the effects of arterial afterload and diastolic dysfunction on aortic valve hemodynamics. This important study demonstrates that reduction of afterload and LV filling pressures with nitroprusside allows discrimination of patients with moderate rather than severe AS, and finds a variable role of afterload among patients with LF compared with normal flow LG severe AS with preserved LVEF. Variability in clinical outcomes reported in other studies for operated and unoperated patients with LG severe AS with preserved LVEF likely relates to the heterogeneity of the group, and reinforces the need to better define hemodynamics among these patients.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Valvular Heart Disease, Acute Heart Failure

Keywords: Aortic Valve, Aortic Valve Stenosis, Arterial Pressure, Atrial Pressure, Blood Pressure, Cardiac Output, Cardiac Catheterization, Constriction, Pathologic, Electric Impedance, Heart Failure, Heart Valve Diseases, Hemodynamics, Nitroprusside, Pulmonary Artery, Stroke Volume, Systole, Vascular Resistance

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