By Michael H. Crawford, MD

Professor of Medicine, Associate Chief for Education, Division of Cardiology, University of California, San Francisco

Dr. Crawford reports no financial relationships relevant to this field of study.

SYNOPSIS: A study of patients with normal flow, low gradients, normal left ventricular systolic function but with calculated aortic valve areas <1.0 cm2 showed that about half of them progressed to severe aortic stenosis during the 25-month median follow-up period.

SOURCE: Chadha G, Bohbot Y, Lachambre P, et al. Progression of normal flow low gradient “severe” aortic stenosis with preserved left ventricular ejection fraction. Am J Cardiol 2020;128:151-158.

Patients with aortic stenosis (AS) who have normal left ventricular (LV) ejection fraction (EF), normal flow (stroke volume index > 35 mL/m2 measured at the LV outflow tract), a mean pressure gradient lower than 40 mmHg, but a calculated aortic valve area (AVA) of < 1.0 cm2 often are referred to as normal flow, low gradient, severe AS (NF-LG-SAS). Their management is controversial. Researchers from three academic medical centers in Belgium and France performed a retrospective observational study that included such patients who also had undergone a second follow-up echocardiogram after at least six months between 2005 and 2015.

The authors excluded patients with more than mild aortic or mitral regurgitation and patients who underwent aortic valve replacement (AVR) between the two echocardiographic exams. The resulting study group consisted of 96 patients (mean age, 79 years; 38% men) with a Charlson Comorbidity Index score averaging 3 and a EuroSCORE II averaging 2.01. The median time between the two echoes was 25 months (interquartile range, 15-52 months). As expected, the severity of AS progressed. Mean aortic pressure gradient increased from 28 to 39 mmHg, peak aortic jet velocity increased from 3.46 to 4.01 m/s, and calculated AVA decreased from 0.87 to 0.72 cm2 (all P < 0.001), but there was no significant change in LVEF. During follow-up, 48% of patients exhibited the parameters of SAS, with mean pressure gradients of > 40 mmHg. The authors concluded NF-LG-SAS with preserved LVEF is an intermediate stage between moderate and SAS and requires close follow up.


Current American guidelines recognize six levels of AS: mild, mild to moderate, moderate, moderate to severe, severe, and very severe. Chadha et al concluded NF-LG-SAS is moderate to severe AS, and they recommended watchful waiting for such patients.

The study population was highly selected, in that it was mainly elderly women, 83% of whom had class I-II symptoms, and the remainder had class III-IV symptoms. One could argue that symptomatic patients with NF-LG-SAS should undergo AVR, unless the symptoms were thought to be caused by something else.

Interestingly, 48% progressed to NF-high gradient-SAS in a median of 25 months, but only 27% underwent AVR after the second echo. There may be several explanations for this, but the authors did not include any reasons. The average EuroSCORE II was only 2 and the Charlson Comorbidity Index score was 3. Many patients should have at least been candidates for TAVR, which was available in Europe during the study period.

Perhaps the most interesting finding was the mortality rate was 32%. Thus, some patients may have died before AVR could be considered or actuated. Could earlier AVR have mitigated this high mortality rate? The results of some prior studies have suggested this, but others have supported the watchful waiting approach. I hate to think that elderly women are treated less aggressively compared to men in Europe. During follow up, 15% of patients progressed to low flow-LG-SAS, and one-third developed reduced LVEF (< 50%). These patients may have benefited from earlier AVR if they could be identified from the start.

Faced with one of these patients, I believe the priority is to be sure the gradient measurement is correct. Unless continuous wave Doppler from many angles is employed, the peak gradient may be underestimated. Despite the fact cardiologists conducted this study in academic centers, there could have been true high gradient patients who were missed. Second, it would be wise in such patients to employ other less-often-performed measures of AS severity to be certain severe AS was not missed. There is considerable literature supporting the use of the extent of calcium in the valve on CT imaging as a measure of severity that is directly associated with outcome. Also, BNP levels have been shown to correlate with outcomes. More sophisticated echo measures, such as global longitudinal strain, could be conducted to identify those with subtler LV dysfunction. Finally, cautious exercise testing to identify symptoms likely caused by AS can be performed. Patients whose initial echo shows moderate to severe AS require additional scrutiny to be sure true SAS is not missed before embarking on a course of watchful waiting.