Discordant Echocardiographic Grading in Low Gradient Aortic Stenosis (DEGAS Study) From the Italian Society of Echocardiography and Cardiovascular Imaging Research Network: Rationale and Study Design

Abstract

Background: Low-gradient aortic stenosis (LG-AS) is characterized by the combination of an aortic valve area compatible with severe stenosis and a low transvalvular mean gradient with low-flow state (i.e., indexed stroke volume <35 mL/m²) in the presence of reduced (classical low-flow AS) or preserved (paradoxical low-flow AS) ejection fraction. Furthermore, the occurrence of a normal-flow LG-AS is still advocated by many authors. Within this diagnostic complexity, the diagnosis of severe AS remains challenging.

Objective: The general objective of the Discordant Echocardiographic Grading in Low-gradient AS (DEGAS Study) study will be to assess the prevalence of true severe AS in this population and validate new parameters to improve the assessment and the clinical decision-making in patients with LG-AS.

Methods and analyses: The DEGAS Study of the Italian Society of Echocardiography and Cardiovascular Imaging is a prospective, multicenter, observational diagnostic study that will enroll consecutively adult patients with LG-AS over 2 years. AS severity will be ideally confirmed by a multimodality approach, but only the quantification of calcium score by multidetector computed tomography will be mandatory. The primary clinical outcome variable will be 12-month all-cause mortality. The secondary outcome variables will be (i) 30-day mortality (for patients treated by Surgical aortic valve replacement or TAVR); (ii) 12-month cardiovascular mortality; (iii) 12-month new major cardiovascular events such as myocardial infarction, stroke, vascular complications, and rehospitalization for heart failure; and (iv) composite endpoint of cardiovascular mortality and hospitalization for heart failure. Data collection will take place through a web platform (REDCap), absolutely secure based on current standards concerning the ethical requirements and data integrity.

Keywords: Aortic valve calcium score; aortic valve stenosis; diagnosis; dobutamine stress echocardiography; echocardiography.

Figure 1

Usefulness of dobutamine stress echocardiography for clinical decision-making. The “?” indicates the parameters and criteria that needs to be further validated or refined. FR: flow rate (in ml/second); AVA: aortic valve area (in cm²); MG: mean transvalvular gradient (in mmHg); LG-AS: low-gradient severe aortic stenosis (AVA ≤ 1.0 cm² and MG < 40 mmHg); LF: low-flow (stroke volume index < 35 ml/m²); NF: normal flow (stroke volume index ≥ 35 ml/m²): AVA_Proj: projected AVA at normal flow rate (in cm²); SAS: severe aortic stenosis; MDCT: multidetector computed tomography; MDCT_Thr: aortic valve calcium score thresholds measured by MDCT: men > 2000 AU and women > 1200 AU, aortic valve calcium density (i.e., calcium score divided by aortic annulus area) ≥500 AU/cm² in men, ≥300 AU/cm² in women)

Figure 2

Projected aortic valve area calculation derived from resting and low-dose dobutamine echocardiography. Eighty-year-old woman with classical low-flow low-gradient severe aortic stenosis, ejection fraction of 29% and body surface area of 1.55 m². Although stroke volume increased minimally with DSE, the flow rate increased 40% due to shortening of the ejection time, but MG and aortic valve area discordance persisted. In this example, the resting aortic valve area is 0.6 cm² and the flow rate is 137 mL/s. The same measurements obtained during inotropic stress with low dose dobutamine give an aortic valve area of 0.7 cm² and flow rate of 192 mL/s. Therefore, the flow rate has not normalized to at least 250 mL/s. The rate of increase in aortic valve area per unit change in flow rate is then derived from the two sets of data dividing the change in aortic valve area by the change in flow rate from rest to stress (slope of the line) = 0.002. Accordingly, the projected aortic valve area at the normalized flow rate equates to 0.8 cm², indicating true severe aortic stenosis

Figure 3

Measurement of aortic valve calcification by multi-detector computed tomography. Noncontrast multislice computed tomography showing axial view of the aortic valve, the axial multiplanar reformat images from left ventricular outflow tract to aortic direction (a) with any calcification highlighted in pink by the software (bone, coronary arteries, aorta, mitral annulus, (b). The region of the aortic valve is assessed in contiguous axial slices during held inspiration, at 120 kV tube voltage, pitch adjusted to heart rate (average 0.7), 64 mm × 0.6 mm collimation, and reconstruction slice thickness of 3 mm and increment of 1.5 mm. State-of-the-art dose reduction strategies including adjusting tube current to chest wall morphology, prospective electrocardiographic gating, and dose modulation should be used

Figure 4

Summary scheme of the mandatory and optional exams of the Discordant Echocardiographic Grading in Low-Gradient Aortic Stenosis study