Accurate Assessment of Aortic Stenosis

Abstract

HomeCirculationVol. 129, No. 2Accurate Assessment of Aortic Stenosis Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissionsDownload Articles + Supplements ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toSupplemental MaterialFree AccessResearch ArticlePDF/EPUBAccurate Assessment of Aortic StenosisA Review of Diagnostic Modalities and Hemodynamics Neelakantan Saikrishnan, PhD, Gautam Kumar, MBBS, MRCP(UK), Fadi J. Sawaya, MD, Stamatios Lerakis, MD and Ajit P. Yoganathan, PhD Neelakantan SaikrishnanNeelakantan Saikrishnan From the Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University, Atlanta, GA (N.S., S.L., A.P.Y.); Emory University, Department of Medicine, Division of Cardiology (G.K., F.J.S., S.L.); and Atlanta VA Medical Center, Department of Medicine, Division of Cardiology, Decatur, GA (G.K.). Search for more papers by this author , Gautam KumarGautam Kumar From the Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University, Atlanta, GA (N.S., S.L., A.P.Y.); Emory University, Department of Medicine, Division of Cardiology (G.K., F.J.S., S.L.); and Atlanta VA Medical Center, Department of Medicine, Division of Cardiology, Decatur, GA (G.K.). Search for more papers by this author , Fadi J. SawayaFadi J. Sawaya From the Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University, Atlanta, GA (N.S., S.L., A.P.Y.); Emory University, Department of Medicine, Division of Cardiology (G.K., F.J.S., S.L.); and Atlanta VA Medical Center, Department of Medicine, Division of Cardiology, Decatur, GA (G.K.). Search for more papers by this author , Stamatios LerakisStamatios Lerakis From the Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University, Atlanta, GA (N.S., S.L., A.P.Y.); Emory University, Department of Medicine, Division of Cardiology (G.K., F.J.S., S.L.); and Atlanta VA Medical Center, Department of Medicine, Division of Cardiology, Decatur, GA (G.K.). Search for more papers by this author and Ajit P. YoganathanAjit P. Yoganathan From the Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University, Atlanta, GA (N.S., S.L., A.P.Y.); Emory University, Department of Medicine, Division of Cardiology (G.K., F.J.S., S.L.); and Atlanta VA Medical Center, Department of Medicine, Division of Cardiology, Decatur, GA (G.K.). Search for more papers by this author Originally published14 Jan 2014https://doi.org/10.1161/CIRCULATIONAHA.113.002310Circulation. 2014;129:244–253is corrected byCorrectionIntroductionAortic valve (AV) stenosis is one of the most common valvular diseases and is the third most common cardiovascular disease in developed countries. It occurs in ≈2.8% of patients ≥75 years of age and can occur because of degenerative calcification and congenital valvular defects such as bicuspid AVs or rheumatic disease.1–3 Calcific aortic stenosis (AS) is associated with increased leaflet stiffness and a narrowed AV orifice, resulting in increased pressure gradients across the valve. The presence of a bicuspid AV significantly increases the risk of AS.4 The natural history of AS is a prolonged asymptomatic period, with progressive reduction of the AV orifice area due to sclerosis initially, culminating in calcific AS. This is accompanied by a corresponding increase in the transaortic pressure gradient (ΔP) and myocardial pressure overload. Through the preload reserve, the left ventricle (LV) compensates for the increased workload until the sarcomeres stretch to their maximum diastolic length. Once the preload reserve is exhausted, increases in afterload are accompanied by a reduction in stroke volume (SV), resulting in afterload mismatch. Ultimately, this causes LV hypertrophy, associated with an enlargement of cardiac myocytes and increased LV wall thickness.5 Initial diagnosis of AS typically occurs during routine physical examination with the presence of a heart murmur, click, or other abnormal sounds, but undiagnosed patients may experience the onset of severe symptoms such as angina, syncope, and heart failure. Without intervention, patient mortality typically occurs within 5 years of the onset of symptoms.6–11 Multiple studies and reviews have focused on the clinical aspects of this disease, including disease progression, markers of disease severity, treatment guidelines, and outcomes.1–3,6,12–16 Very few reviews have focused on the hemodynamic principles underlying AS and on comparing data obtained across different imaging modalities.17–19 This article aims to provide cardiologists with a comprehensive review of the hemodynamic concepts associated with AS, in addition to identifying potential inconsistencies in diagnosis while comparing data from different techniques. A careful understanding of these fundamental concepts will enable consistent diagnosis of AS patients. In addition, potential inconsistencies in the diagnosis of patients with low-flow, low-gradient AS and the role of in vitro studies in improving the understanding of AS will also be presented.Pathophysiology of ASThe native AV experiences a complex mechanical environment, including leaflet stretch, fluid shear stress, bending stresses, and pressure forces. The forces experienced by the leaflet vary spatially and temporally over the cardiac cycle and may be altered significantly because of disease. Calcific AS was initially believed to be a passive disease associated with the wear and tear of valve tissue due to aging. However, multiple studies have shown that AV calcification is the result of active inflammatory processes, mediated by hemodynamic and genetic factors. The disease progresses from endothelial damage due to mechanical stresses, lipid penetration, and accumulation in areas of inflammation, followed by fibrosis, leaflet thickening, and finally calcification.20–23Altered mechanical stimuli on the AV leaflets may lead to valvular endothelial dysfunction and deposition of oxidized low-density lipoprotein, which may trigger infiltration of macrophages and other cytokines, resulting in inflammation. Further, the trilayered structure of the AV matrix may be disrupted because of an imbalance in the expression of matrix metalloproteinases, their inhibitors, cathepsins, collagen, and elastin, with the resulting matrix being more disorganized. Eventually, the expression of bone-related proteins increases in the valve extracellular matrix that results in osteoblastic differentiation of the valve interstitial cells. This osteogenic differentiation of valve cells is speculated to be brought about by multiple signaling pathways expressing RunX2, osteoprotegerin, elevated alkaline phosphatase, serum calcium, and phosphate levels, which are key proteins involved in bone turnover and vascular calcification. Although a complete picture of the molecular pathways involved in aortic valve calcification (AVC) and subsequently AS is still emerging, a detailed understanding of AVC and AS is crucial to the identification of key targets for therapeutic interventions for the prevention and treatment of AS. The reader is referred to comprehensive reviews on the topics of AVC and potential therapeutic interventions for additional information.14,24–26 In particular, the executive summary of the National Heart, Lung, and Blood Institute AS working group is a valuable resource that provides a state-of-the-art understanding of the underlying processes involved in AS.23Hemodynamics of ASFlow through the AV is pulsatile in nature and directly depends on multiple factors, including LV systolic and diastolic function, aortic pressure and compliance, leaflet mobility, and LV geometry and chronotropy. When ventricular pressure exceeds aortic pressure at the start of ventricular systole, the AV leaflets open to permit flow through the valve. Cardiac output (CO) increases until peak systole, beyond which it starts to decrease. ΔP and flow rate through the valve vary with the time point in the cardiac cycle. In AS, this temporal variability may play a key role in disease diagnosis. Figure 1 shows the data obtained from various imaging modalities and how the pulsatility of the flow through the AV affects these measurements.Download figureDownload PowerPointFigure 1. Comparison of data obtained from cardiac catheterization, Doppler echocardiography, in vitro studies, and MRI studies. AAo indicates ascending aorta; CO, cardiac output; LVOT, left ventricular outflow tract; and VC, vena contracta.Flow through a stenotic AV is well approximated by flow through a convergent orifice (Figure 2). The narrowed AV orifice and restricted leaflet opening create a hemodynamic nozzle, causing acceleration of blood through the valve—from a low velocity (V1 < 1 m/s) in the LV outflow tract (LVOT) to the maximum velocity (V2 > 1 m/s) at the vena contracta (VC) of the jet. The area formed by the free edges of the AV leaflets is known as the geometric orifice area (GOA) of the valve, whereas the area of the flow jet at the VC is known as the effective orifice area (EOA). The pressure difference between the LVOT and EOA is referred to as ΔPmax. Fluid mechanics theory shows that GOA is always greater than or equal to EOA (they are equal when GOA and LVOT area are equal).18,27 The ratio of the EOA to the GOA is known as the contraction coefficient (cc). The contraction coefficient depends on the 3-dimensional shape of the valve leaflets, where cc is significantly lower for flat valves than for doming bicuspid valves.28 Also, the VC always occurs downstream of the valve orifice (Figure 2).Download figureDownload PowerPointFigure 2. Schematic of flow through a stenotic aortic valve. Formulas for the contraction coefficient and EOA using the continuity equation are also shown. AAo indicates ascending aorta; EOA, effective orifice area; GOA, geometric orifice area; LVOT, left ventricular outflow tract; VC, vena contracta; and VTI velocity time integral.Further into the ascending aorta (AAo), some amount of the kinetic energy of the blood is converted back to potential energy, resulting in an increase in the local pressure, and this is known as the pressure recovery effect.18,29–32 The pressure difference between the LVOT and AAo is referred to as ΔPrec. Thus, ΔPmax > ΔPrec owing to pressure recovery. Many in vitro studies have also investigated the effects of pressure recovery, aiming to resolve the discrepancies between catheter and Doppler measurements.29,33,34 These studies clearly demonstrated the role of pressure recovery in the underestimation of the severity of AS by catheterization in comparison with Doppler measurements. In vitro studies suggest that the recovered pressure drop correlates directly to the ventricular workload, but the physiological impact of this is still unclear.34Assessment of ASIn the EuroHeart survey, AS was the most common valvular disease among patients referred to hospitals, accounting for 34% of all native valve disease and 43% of all single valve disease.35 The natural history of AS is characterized by a long latent period of progressive valvular obstruction followed by the onset of symptoms. During the asymptomatic phase, the main predictor of event-free survival is the maximal jet velocity.7,11 The onset of symptoms (angina, syncope, and dyspnea) in severe AS is a harbinger of subsequent clinical events.6 Although asymptomatic patients have good clinical prognosis during the latent period, symptomatic patients who may be excluded because of multiple comorbidities have a very poor prognosis without intervention.36,37A critical component of accurate diagnosis is the integrated assessment of the patient with the use of these various modalities. In addition to physical examination, a combination of the results of imaging modalities provides the ability to consistently diagnose patients. However, a fundamental understanding of the metrics and measurements provided by these various modalities is also critical in this integrated diagnostic approach. To confirm the presence of AS, various imaging modalities may be used. Transthoracic echocardiography is the gold standard modality for initial diagnosis and subsequent evaluation of AS. However, other imaging modalities may also be used, depending on the indications from transthoracic echocardiography. The following sections describe the use of various modalities used to diagnose AS. Table 1 summarizes some key advantages and disadvantages of using various modalities in the diagnosis of AS.Table 1. Comparison of Advantages and Disadvantages of Modalities Used for Diagnosis of ASDiagnostic ModalityAdvantagesDisadvantagesDoppler echocardiography• Non/minimally invasive• Moderate spatial resolution• Provides both flow and anatomy• Does not provide pressure directly• Need LVOT measurements• Need good imaging windows for accurate measurementsCardiac catheterization• Direct pressure measurement• Can resolve inconsistencies in echo diagnosis• Invasive• Time-averaged CO measure• Cannot provide valve anatomyCT• Highest spatial resolution• Can provide 3D anatomy• No hemodynamic data• Radiation exposureMRI• Provides 3D anatomy and flow• No radiation risks• Low spatial and temporal resolution• Aliasing in severe AS• ExpensiveAS indicates aortic stenosis; CO, cardiac output; and CT, computed tomography.Role of EchocardiographyThe severity of AS can be assessed with the use of Doppler echocardiography by measuring AS jet velocity, and the AV area can be assessed by use of the continuity equation. ΔPmean can be assessed by use of the Bernoulli equation.38,39 Early in vitro studies verified the use of the Bernoulli equation against gold standard catheterization data to assess ΔP.40–42 Accurate data recording also requires multiple acoustic windows to determine the highest AS jet velocity. Apical (5-chamber view), suprasternal, or right parasternal views most frequently yield the highest velocity. Yoganathan43 studied the flow characteristics through stenotic AVs by using flow visualization, laser Doppler anemometry, continuous-wave Doppler ultrasound, and color Doppler ultrasound to analyze jet characteristics, turbulent intensities, and peak velocities, and showed that Doppler measurements may be needed in multiple directions to accurately assess the severity of AS.Transthoracic echocardiography is useful in determining AV morphology, concomitant aortic regurgitation, LV function, aortic pathologies, and other valvular abnormalities. Transthoracic echocardiography may distinguish between stenosis caused by hypertrophic cardiomyopathy, valvular or subvalvular stenosis, but in some cases, transesophageal echocardiography may be needed. Dobutamine stress echocardiography is appropriate for patients with low-flow, low-gradient AS with low LV ejection fraction (EF) and has received a Class IIa (Level of Evidence: B) recommendation in the American College of Cardiology/American Heart Association-European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines.44–46The AS jet velocity can be directly measured from continuous-wave Doppler tracings through the AV. ΔPmean and ΔPmax can be calculated by using the simplified Bernoulli equation, which assumes a proximal velocity V1 < 1 m/s. ΔPmean must be computed from instantaneous ΔP after using the Bernoulli equation because of the square term in this equation. EOA is calculated by using the continuity equation, because the volume of blood passing through the LVOT must equal the volume of blood ejected at the EOA. The LVOT diameter is measured from a parasternal long-axis view of the LVOT, and the LVOT velocity time integral (VTI) is obtained using a pulsed-wave Doppler signal. From these, the EOA can be calculated as the product of LVOT cross-sectional area and LVOT VTI divided by the continuous-wave Doppler VTI (Figure 2). This is the fluid volume at the VC, because continuous wave measures the highest velocity in the line of interrogation. Other hemodynamic measurements of AS such as energy-loss index, AV resistance, valvuloarterial impedance, and LV stroke loss may also be calculated from the acquired data.38,47Table 2 lists various indices and metrics used for the diagnosis of AS. The reader is referred to the review article by Pibarot and Dumesnil47 and the EAE/ASE recommendations for echo assessment of AS by Baumgartner and colleagues for detailed descriptions of these alternate hemodynamic metrics that may be used to assess AS.38 However, the robustness of these derived metrics needs to be demonstrated in longitudinal data from prospective studies.Table 2. Various Hemodynamic Metrics Used for Assessment of AS and Their Cutoff Values for Severe ASMetricUnitsMethodSevere AS CutoffAS jet velocity*m/sDirect measure> 4.0Mean pressure gradient*mm HgDirect measure (Cath)Bernoulli equation (Echo)> 40EOA*cm2Gorlin equation (Cath)Continuity equation (Echo)< 1.0Indexed EOA*cm2/m2EOA normalized by BSA< 0.6Dimensionless index (DI)*NoneRatio of LVOT velocity and VC velocity< 0.25Energy loss indexcm2/m2Indexed EOA accounting for ascending aorta size< 0.5–0.6Valvuloarterial impedancemm Hg·m–1·m2Global systolic LV load, including arterial pressure4.5–5AV resistancedynes·s·cm–5Resistance of AV to flow> 280Projected valve area at normal flowcm2Estimated EOA at normal flow< 1.0Calcium scoreAUMeasured from CT data> 1651AU indicates Agatston Units; BSA, body surface area; Cath, catheterization; Echo, echocardiography; and VC, vena contracta.*Metrics used for clinical assessment. Metrics without an asterisk still need validation.An exception is the energy-loss index, defined as ELI = [EOA×Aa/(Aa−EOA)]/BSA, where Aa is the aortic area at the level of the sinotubular junction, BSA is the body surface area, and ELI is the energy-loss index.48 This index accounts for pressure recovery in the ascending aorta by including the ascending aortic size in the calculations. Recent work by Bahlmann and colleagues49,50 from the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, showed that energy-loss index improved the prediction of AV events by 13%, suggesting that this may be a promising parameter to be used clinically.Role of Cardiac CatheterizationIn the 1950s and 1960s, invasive hemodynamic studies were essential for understanding the physiology and pathophysiology of valvular heart disease. With the advent of echocardiography in the 1980s and 1990s and the evolution of percutaneous coronary intervention, the role of the cardiac catheterization laboratory slowly shifted to diagnosing and treating coronary artery disease. However, in the past few years, the development of percutaneous approaches to valvular heart disease has led to a renaissance of invasive hemodynamic studies.According to the American College of Cardiology/American Heart Association Guidelines for the management of patients with valvular heart disease, coronary angiography may be sufficient before valve replacement if clinical and echocardiographic data consistently indicate severe AS.44 On the other hand, any discrepancies between these must be reconciled by using cardiac catheterization so that the patient is not deprived of the potential benefit of aortic valve replacement (AVR) for severe symptomatic AS. Additionally, catheterization with dobutamine infusion may be used in patients with low-flow, low-gradient AS and LV dysfunction.51Typically, ΔP is measured between the LVOT and the AAo by using double-lumen fluid-filled catheters for simultaneous LV and aortic pressure measurements. Micromanometer-tipped catheters may be considered when extensive artifacts degrade the quality of tracings from the fluid-filled catheters or when additional precision is necessary for research. Pullback gradients are inaccurate for diagnostic purposes. CO is assessed in the cardiac catheterization laboratory by 2 principal methods: Fick and thermodilution.52 The Fick method relies on obtaining arterial and mixed venous saturations, hemoglobin level, and oxygen consumption. The thermodilution method relies on injecting cold or room-temperature saline and measuring the change in temperature as this passes from the injection port to the thermistor on the Swan-Ganz catheter.Once ΔP and CO are obtained, the Gorlin equation is used to calculate the EOA.53 However, this area differs from the corresponding echocardiographic measurement owing to the difficulty in precisely positioning the aortic side catheter at the VC of the flow jet. Hence, catheterization ΔP is equivalent to ΔPrec. Additionally, ΔPmean and ΔPpeak may be measured, whereas only the mean CO is available for calculation. A detailed description of the potential errors associated with these measurements is presented later. Despite the potential for inaccuracies, it is recommended that the operator perform a quick on-the-fly calculation of EOA by using the simplified Hakki equation.54Role of Computed TomographyComputed tomography (CT) provides the highest-resolution anatomic data of the AV in calcific AS. Additionally, CT provides the best assessment of calcification on the valve leaflets and annulus among all imaging modalities. Although cardiac CT was initially used to detect and quantify coronary artery calcification,55,56 its applicability to assess AVC was also demonstrated in early studies.57–59 Currently, multidetector CT scanners are most commonly used because of their lower cost and superior spatial and temporal resolution.60In CT scans, calcific deposits are displayed as bright regions within the image, and AVC is quantified by using the Agatston method. Here, calcified foci are defined as areas of ≥3 pixels with attenuation >130 Hounsfield units. The metric of interest is the calcium score that is measured by multiplying the measured area by an attenuation coefficient based on the peak attenuation in the region, and is expressed in Agatston Units (AU).55 A recent study showed that a calcium score <700 AU excluded severe AS with a high negative predictive value, whereas a score >2000 AU suggested severe AS. A threshold of 1651 AU provided the best combination of sensitivity (80%) and specificity (87%), particularly for patients with depressed EF.61 Other methods have been proposed where a volumetric score can be calculated by 3-dimensional interpolation of an CT-image stack62; however, the calcium score remains the primary metric for assessing AVC.Despite the superior spatial resolution afforded by CT, current clinical guidelines do not recommend CT scans for the diagnosis of AS. This is because CT can only provide the GOA of the valve and cannot provide any hemodynamic data such as ΔP or CO in isolation. Hence, EOA cannot be calculated by using CT. Although studies have shown strong correlations between amount of AVC and severity of stenosis,63–65 other studies have not been able to demonstrate similar correlations,47,66 which may be because AVC only accounts for leaflet mobility and does not address AS in totality including the LV. Second, CT typically provides a view of the AV at peak systole, whereas the total workload on the heart is a result of the total flow through the valve during ventricular systole. Hemodynamic measures such as ΔPmean account for this fact by using data across the entire systolic duration. Thus, planimetered systolic GOA measurements may not accurately represent AS severity.18 Finally, CT scans involve exposure to x-ray radiation; hence, cardiologists may prefer to use other noninvasive imaging tools to assess AV functionality.Despite these findings, CT still provides high spatial resolution data that may be necessary for certain applications. Additionally, CT is the only modality that provides direct noninvasive assessment of the amount of AVC. Because calcification is the primary underlying pathology of AS, a direct assessment of AVC remains an alluring target for clinicians. Further, clinical studies have suggested that AVC is a marker for cardiovascular morbidity.8 Thus, calcium scoring may prove to be a worthy complement to echocardiographic/catheter evaluation of AS.61,67CT has gained prominence recently in the treatment of AS with the use of transcatheter aortic valve replacements (TAVRs). CT data may provide the best assessment of the level of AVC and the size of the native valve annulus and sinuses. Hence, preoperative CT data may be used to select an appropriate TAVR size. In addition, these data may be used to predict transcatheter valve deployment shape and geometry preoperatively.68 Recent clinical reviews have shown the significance of addressing paravalvular leakage, and CT may be a key imaging modality to enable the development of such technology.69 Although such technology is not used in clinical practice currently, these promising approaches may signal increased relevance for CT in the assessment and treatment of AS.Role of MRIMRI has been used to a much lesser extent in the diagnosis of AS. The attractiveness of MRI lies in the avoidance of radiation exposure and in the ability to obtain both anatomic and hemodynamic measurements and full 3-dimensional information provided by the modality. Thus, both the GOA and the EOA of the valve can be measured with a single modality, while also capturing any pressure recovery effects in the ascending aortic flow. Additionally, MRI does not require imaging windows to precisely identify the valve jets. On the other hand, the inherent disadvantages of MRI include the inability to accurately identify calcification, signal voids due to flow turbulence, lower spatial resolution in comparison with CT, imaging artifacts due to implanted medical devices, increased scan times, and higher costs. Despite these limitations, multiple studies have sought to investigate the use of MRI for measuring the EOA, by using MRI data in combination with either the continuity or modified forms of the Gorlin equation to calculate EOA.70–75 Studies have also attempted to directly measure the vena contracta of the peak systolic jet in AS patients by calculating the width of the jet with the use of velocity data. This direct measurement does not rely on any assumptions that may be necessary while calculating EOA from catheterization or echocardiography.39,76 Although these studies have shown good correlation between MRI-derived EOA measurements with standard of care echocardiography-derived EOA, these have been limited to small sample sizes, and the disadvantages of MRI listed above have prevented the widespread acceptance of MRI as a diagnostic tool for AS.Potential for Inconsistencies in Diagnostics and GuidelinesInconsistencies in the metrics used to diagnose AS may lead to suboptimal treatment of AS patients. The following sections describe various sources of potential errors in calculating metrics from diagnostic data, and the impact of these inconsistencies on clinical guidelines and patient outcomes. These sections also highlight results from in vitro studies that have provided the ability to parametrically study the effects of AS by isolating various factors that may affect disease processes and diagnostic accuracy. It must however be noted that it may not be possible to accurately assess all patients by using a single parameter or metric, and an integrated approach may be necessary by recognizing AS as a disease continuum.Gorlin EquationThe Gorlin equation was derived for use with cardiac catheterization data in the assessment of severity of AS. This equation provides a mathematical formulation relating ΔP and flow rate (Q) to the GOA, and is derived by combining the continuity and orifice equations.53Download figure ((1)) where Q is flow through the AV (in mL/s); g is the acceleration due to gravity, ΔP is the pressure drop between the LVOT and VC in cm H2O, and cv accounts for viscous losses and turbulence. The constant of 51.6 is derived by using g (980.67 cm/s2) and converting ΔP in cm H2O to mm Hg (1 mm Hg = 1.35 cm H2O). In the original article, the empirical constants were derived for the pulmonary valve, and it was suggested that this could be used for the AV (cc = 0.85 and cv = 1). Thus, the original Gorlin formulation wasDownload figure ((2)) This original formulation by Gorlin and Gorlin, based on autopsied valves provided an equation for the GOA as a function of the flow through the valve and the pressure drop across the valve measured between the LVOT and VC. However, some previous studies have mistakenly assumed that the Gorlin formulation provides the EOA, which is most often used as the AV area.77,78 Alternatively, it has also been proposed that the Gorlin equation assumes that EOA and GOA are the same,79 which is also incorrect. The correct EOA equation that is independent of the contraction coefficient cc is:Download figure ((3)) Multiple in vitro studies have been focused on identifying methods to accurately calculate cc based on the valve opening to calculate EOA.28,80 MRI, echocardiography, or CT can provide the GOA directly without assumption of cc; hence, the Gorlin equation need not be used to calculate GOA. However, the direct measurement of GOA using these modalities can be inaccurate because artifacts due to valve calcification and limited spatial resolution. Additionally, the use of constant 44.3 instead of 51.6 in the Gorlin formulation owing to the interchangeable use of GOA and EOA can result in erroneous diagnosis of AS; hence, the correct quantity must be used clinically. Avoiding the use of an assumed value of cc is crucial to correctly using the Gorlin equation for diagnostic purposes.EOA Versus GOAAs described earlier, the GOA is the area forme