Aortic Stenosis (AS) is a critical heart condition that necessitates precise evaluation for effective patient care. Echocardiography, a primary diagnostic tool, relies on several key measurements to determine the severity of AS. Among these, the Mean Pressure Gradient (MPG) stands out as a crucial indicator. While Peak Velocity (PVel) and Aortic Valve Area (AVA) are also significant, understanding the definition of MPG in the context of AS is paramount for grasping the full picture of this condition. This article delves into the definition of MPG within aortic stenosis, clarifies potential ambiguities in its interpretation, and emphasizes its role alongside other parameters for accurate diagnosis and management.
Understanding the Nuances of Aortic Stenosis Evaluation
Grading the severity of aortic stenosis is fundamental for guiding treatment strategies and predicting patient outcomes. Echocardiography is the cornerstone of this assessment, employing peak velocity (PVel), mean pressure gradient (MPG), and aortic valve area (AVA) as its main pillars. These parameters are ideally in agreement, defining severe AS as a condition characterized by a peak velocity exceeding 4 m/sec, an MPG greater than 40 mmHg, and an AVA less than 1 cm².
However, clinical practice reveals a more complex reality. A significant proportion of patients, up to a third, exhibit discrepancies in these measurements, leading to what is known as discordant AS grading. Furthermore, a subset of patients presents with paradoxical low-flow, low-gradient severe aortic stenosis despite maintaining a preserved ejection fraction. This article aims to clarify the potential pitfalls in AS evaluation that can lead to misdiagnosis, discuss the prevalence and prognosis of discordant grading, and underscore the emerging role of computed tomography in providing an independent assessment of AS severity. It’s important to note that this discussion will focus on patients with normal to preserved ejection fraction, setting aside the complexities of assessing AS in those with reduced ejection fraction.
Table 1. Echocardiographic and Computed Tomography Grading of Aortic Stenosis Severity
| Echo Parameters | Sclerosis | Mild AS | Moderate AS | Severe AS |
|---|---|---|---|---|
| Peak Velocity (m/sec) | <2.5 | 2.5-3 | 3-4 | >4 |
| Mean Gradient (mmHg) | Normal | <20 | 20-40 | ≥40 |
| AVA (cm²) | Normal | ≥1.5 | 1-1.5 | <1 cm² |
| Calcium Scoring (AU) | Male ≥2,065 Female ≥1,275 |
Common Pitfalls in Aortic Stenosis Assessment
Discordant grading arises when echocardiographic parameters suggest conflicting levels of AS severity—for instance, an AVA indicating severe AS (<1 cm²) while the MPG is below the severe threshold (<40 mmHg), or conversely, an AVA suggesting moderate AS (≥1 cm²) with an MPG in the severe range (≥40 mmHg). The former scenario, characterized by a small AVA and a lower MPG, is more frequently encountered in clinical practice. It’s also important to recognize the close relationship between MPG and PVel; these parameters are highly collinear and often used interchangeably to assess AS severity. Therefore, for simplicity, this discussion will primarily focus on MPG.
Calculating AVA involves three measurements, each susceptible to error. The measurement of the Left Ventricular Outflow Tract (LVOT) diameter is perhaps the most critical source of variability. Proper technique mandates measuring the LVOT diameter in the parasternal long-axis view, utilizing zoom mode during mid-systole, and repeating the measurement multiple times (three to five times is recommended) to ensure accuracy. The precise location of LVOT diameter measurement—at the aortic annulus (leaflet insertion level) or slightly below (5-10 mm apical)—remains a topic of debate. Current guidelines from the European Association of Cardiovascular Imaging and the American Society of Echocardiography [1] advocate for annulus-level measurement due to its enhanced reproducibility and alignment with the anatomical plane of pulse Doppler measurements. This annulus-level approach is our preferred practice. It is crucial to appreciate the significant impact of even small errors in LVOT diameter measurement; a mere 1 mm difference can alter the calculated AVA by 0.1 cm². Severe calcification and suboptimal image quality can further complicate accurate LVOT diameter measurement. Considering the influence of body size on anatomical structures, including the LVOT, a safeguard formula incorporating body surface area (BSA) has been proposed (theoretical LVOT diameter = 5.7 * BSA + 12.1) [2]. This formula provides a reference, with a standard deviation of 1 mm, indicating the expected range of variation in LVOT diameter relative to BSA.
The second potential source of error lies in measuring aortic valve TVI using continuous-wave Doppler. While PVel and MPG are derived from the same Doppler acquisition, achieving the highest aortic velocity necessitates careful technique and the use of multiple acoustic windows. In addition to the apical view, the right parasternal, suprasternal, and subcostal views should be routinely employed. Failure to utilize these alternative views can lead to underestimation of AS severity in a significant proportion of patients (20% or more) [3]. While dedicated crystal probes were traditionally used, modern echocardiographic systems with combined 2D/Doppler probes can achieve comparable results, particularly when the 2D probe is utilized in the right parasternal view.
Underestimation of the importance of LVOT TVI, the third parameter in AVA calculation, is another common pitfall. Improper Doppler sample placement can significantly skew results. Positioning the sample too distal to the aortic orifice overestimates AS severity, while positioning it too proximal, within the flow acceleration zone, underestimates severity. Optimal placement involves adjusting the Doppler sample position to obtain a clear Doppler signal, ideally with a closure click (though this may be absent in very severe AS), and without capturing the opening click.
Finally, a small AVA (<1 cm²) can be a normal finding in patients with small body size. In such cases, indexing AVA to BSA is recommended, with a threshold of 0.6 cm²/m² for severe AS. However, BSA correction should be judiciously applied, reserved for individuals at extremes of body size (e.g., small elderly women or exceptionally tall individuals) and avoided in obese patients. Height-adjusted thresholds are not yet established.
Prevalence and Prognosis of Discordant AS Grading
Despite meticulous adherence to recommended echocardiographic techniques, discordant grading in AS remains a common clinical challenge, observed in 20-30% of patients. Variability in reported incidence and prognostic implications is partly attributable to inconsistent classification criteria across studies and potential measurement errors. The Quebec team’s seminal work [4] utilized stroke volume index to categorize patients, with a threshold of 35 ml/m² gaining widespread acceptance, although formal validation is lacking. Conversely, the SEAS trial [5] defined discordance based solely on AVA and MPG discrepancies, independent of flow parameters.
A more clinically relevant approach classifies patients initially by concordance between AVA and MPG, and subsequently by flow (stroke volume index). Among patients with AVA <1 cm², this framework delineates four distinct groups (Figure 1). Patients with concordantly severe AS (small AVA and high MPG) are readily identified. However, the remaining groups, particularly those with low gradient and either normal or low flow, present diagnostic ambiguity. The latter group closely aligns with the paradoxical low-flow severe AS entity described by the Quebec group [4]. Data from the Mayo Clinic [6], encompassing 1,704 patients with AVA <1 cm², reveals that 24% exhibited discordant grading (AVA <1 cm² and MPG <40 mmHg). The majority of these discordant cases (21% of the total cohort) had normal flow, while only 3% demonstrated low flow. This study underscores the substantial prevalence of discordant grading and highlights that normal-flow discordant AS is more common than low-flow discordant AS. Importantly, the Mayo Clinic study also demonstrated that the subgroup with discordant grading (AVA <1 cm², MPG <40 mmHg) and low flow had the poorest prognosis (Figure 2), reinforcing the prognostic significance of flow in AS, regardless of the underlying cause of reduced flow. The initially proposed phenotype of an elderly woman with atrial fibrillation, preserved ejection fraction, and left ventricular hypertrophy as the typical presentation of low-flow paradoxical severe AS appears to be more of an exception than the rule. Rare instances of discordant grading with AVA >1 cm² and MPG >40 mmHg are often observed in patients with bicuspid aortic valves and larger LVOT/annulus dimensions, and these cases are generally classified as severe AS.
Figure 1. Classification of Patients with an Aortic Valve Area <1 cm² (and preserved ejection fraction) into Four Groups according to Mean Pressure Gradient (MPG) and Stroke Volume Index (SVI)
Figure 2. Prognosis of the Four Subsets as Defined in Figure 1. The Patients with Low Flow (stroke volume index <35 ml/m²) and Low Gradient (<40 mmHg) Incurred the Worst Prognosis (from reference [6])
The Role of Computed Tomography in AS Severity Assessment
The frequent occurrence of discordant grading and the prognostic implications of low flow raise a critical question: do patients with discordant grading truly have severe AS? A central debate in valvular heart disease has revolved around whether management decisions in discordant AS should be guided by AVA (treating as severe AS) or MPG (treating as moderate AS). Flow considerations further complicate this decision-making process. When resting echocardiography yields inconclusive results, additional diagnostic modalities become essential.
Computed tomography (CT), increasingly utilized in pre-TAVI (Transcatheter Aortic Valve Implantation) evaluation, has provided valuable insights into aortic annulus anatomy. CT imaging has demonstrated that the LVOT and aortic annulus are not circular but rather oval. AVA calculation, which assumes a circular LVOT based on diameter measurement, inherently introduces error. This has led to suggestions of combining CT-derived LVOT area measurements with echocardiographic LVOT and aortic TVI measurements for AVA calculation [7]. While conceptually appealing, this hybrid approach has limitations. Firstly, echocardiography is known to underestimate LVOT annulus diameter by 1-2 mm. Combining CT LVOT area with echo-derived TVIs would likely increase calculated AVA, potentially reducing the prevalence of low-gradient severe AS. Secondly, the established prognostic value of AVA is based on echocardiographic assessment, and the prognostic implications of this hybrid AVA calculation remain uncertain. Thirdly, studies employing CT-derived LVOT area measurements have lacked a definitive reference standard for validation.
Therefore, a more robust approach to resolving discordant grading in AS is the use of a quantitative, flow-independent method to assess AS severity. Aortic valve calcium scoring, performed using computed tomography, offers this valuable characteristic. Aortic valve calcification is the fundamental pathological process driving AS [8]. Unlike vascular calcification, leaflet hydroxyapatite deposition and infiltration are the primary mechanisms of leaflet stiffening and hemodynamic obstruction in AS. CT enables accurate and quantitative in vivo assessment of aortic valve calcification [9]. The methodology is straightforward and widely available. ECG-gated CT scans are acquired from the cardiac apex to base, encompassing the aortic valve, without the need for contrast injection. Semi-automated software identifies calcified areas (tissue density >130 Hounsfield units), typically highlighted in red. The operator then delineates the calcified area specific to the aortic valve, avoiding potential misidentification of mitral annular, aortic wall, or coronary ostial calcifications. This method demonstrates high reproducibility. Quantification is based on the Agatston score (expressed in arbitrary units [AU]), which incorporates calcification area and peak density. Studies have demonstrated a strong correlation between calcium scoring and echocardiographic hemodynamic severity, validating its diagnostic utility for severe AS [10]. Interestingly, thresholds for severe AS calcium scores differ between sexes [11]. For a given degree of aortic valve calcification, women tend to exhibit greater hemodynamic obstruction; in other words, an MPG of 40 mmHg is associated with a lower calcium burden in women compared to men. Sex-specific thresholds for severe AS are approximately 2,000 AU for men and 1,250 AU for women. These findings suggest underlying sex differences in AS pathophysiology, with female leaflets exhibiting greater fibrosis than male leaflets [12]. It’s important to note that these thresholds are not applicable to rheumatic valve disease and require specific validation for bicuspid aortic valves. In a study of 646 patients with moderate to severe AS and preserved ejection fraction [13], discordant grading (AVA <1 cm² and MPG <40 mmHg) was observed in 27%, with the majority (85%) exhibiting normal flow. As anticipated, calcium scoring accurately classified patients with concordant grading. Crucially, in patients with discordant grading, calcium scoring reclassified approximately 50% as having true severe AS, independent of flow status.
Aortic valve calcium scoring and the established sex-specific thresholds have been incorporated into the latest ESC/EACTS guidelines on valvular heart disease [14]. In cases of discordant grading, after excluding potential measurement errors, calcium scoring is recommended as a first-line adjunctive test. A calcium score above the established threshold, in a symptomatic patient, supports a diagnosis of severe AS and warrants consideration of intervention. Conversely, a score below the threshold suggests that severe AS is less likely, potentially favoring conservative management, although the potential benefit of intervention in this scenario remains an area of ongoing investigation. It’s essential to recognize that these thresholds are not absolute cutoffs but rather provide a probability of severe AS. For example, a woman with a calcium score of 3,000 AU is highly likely to have severe AS, while a man with a score of 700 AU is very unlikely to have severe AS.
Key Takeaways
In summary, the critical points regarding MPG definition and AS assessment are:
- Discordant grading in aortic stenosis is a common clinical finding.
- The initial step in evaluating discordant grading is to meticulously review echocardiographic measurements for potential errors.
- BSA adjustment of AVA should be reserved for patients at extremes of body size and avoided in obese individuals.
- Among patients with discordant grading (AVA <1 cm² and MPG <40 mmHg), normal-flow presentations are significantly more frequent than low-flow presentations.
- Flow parameters, while prognostically relevant, do not definitively resolve diagnostic uncertainty in discordant AS.
- Transthoracic echocardiography alone may be insufficient to determine AS severity in many cases of discordant grading.
- Aortic valve calcium scoring, a quantitative and flow-independent CT-based method, offers a valuable tool for assessing AS severity. Recommended thresholds are ≥2,000 AU in men and ≥1,250 AU in women.
- Intervention is recommended for symptomatic patients with confirmed severe AS, including those diagnosed through calcium scoring in the context of discordant grading.
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