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Learning objectives
To understand the role of cardiac magnetic resonance (CMR) imaging as a diagnostic aid in the assessment of severity of aortic stenosis (AS).
To understand the role of CMR in assessing the remodelling response of the heart to the pressure overload in AS.
Potential of CMR as a risk-stratification tool in the management of AS.
Introduction
Aortic stenosis (AS) is the most common valve lesion requiring surgery in the developed world1 and is common in the elderly, with up to 3% of those over the age of 75 thought to have severe disease.2 With an ageing population, the prevalence of AS is expected to double in the next 20 years.3 AS progresses slowly over many years and is associated with compensatory left ventricular (LV) remodelling (hypertrophy and fibrosis) that is important in the development of symptoms and risk of heart failure.4 Thus, the response of the myocardium to pressure overload may be as important as the severity of the AS. Despite many medical advances, either surgical aortic valve replacement (SAVR) or transcutaneous aortic valve replacement (TAVR) remains the only available effective treatment for this common condition. Currently, intervention is recommended once symptoms or systolic dysfunction develop, but there remains a small risk of sudden cardiac death in the patient with asymptomatic severe AS. Research has therefore been focused on identifying risk-stratification tools for earlier intervention in a select high-risk population, with the ultimate aim of improving outcome.
Cardiac magnetic resonance (CMR) imaging is one such tool that offers accurate and non-invasive assessment of the valve and the myocardium, allowing comprehensive assessment of the effects of AS. The latest European Society of Cardiology (ESC) guidelines identify four categories of AS based on mean gradient, flow and ejection fraction (table 1), and multimodality imaging plays a key role in diagnosis of borderline cases.5
Classification of AS based on 2017 European Society of Cardiology guidelines
It is important to state that echocardiography remains ‘the key technique used to confirm the diagnosis of valvular heart disease, as well as to assess its severity and prognosis’ (ESC guidelines 2017).5 Three-dimensional transthoracic (TTE) or transoesophageal echocardiography (TOE) can provide more accurate measurement of the aortic annulus prior to intervention, and are key in successful transcutaneous valve replacement. However, CMR can offer important complimentary information and ‘in patients with inadequate echocardiographic quality or discrepant results, CMR should be used to assess the severity of valvular lesions… and to assess ventricular volumes, systolic function, abnormalities of the ascending aorta and myocardial fibrosis’ (ESC guidelines 2017).5 It may also play a wider role in risk stratification in the future. A suggested algorithm for the utility of CMR and other imaging modalities is shown in figure 1.
A suggested algorithm for assessment of suspected severe aortic stenosis (adapted from ESC 2017 guidelines). AS, aortic stenosis; AVA, aortic valve area; AVAI, Aortic Valve Area Index; 3D, three-dimensional; CAD, coronary artery disease; DSE, dobutamine stress echo; DVI, dimensionless velocity index; EOA,effective orifice area; ESC, European Society of Cardiology; iECV, indexed extracellular volume fraction; LGE, late gadolinium enhancement; LVEF, left ventricular ejection fraction; MPG, mean pressure gradient; SVI, Stroke Volume Index; TOE, transoesophageal echocardiography.
This article focuses on the clinical applications of CMR in AS. Further information on the physics of the technique and basics of different pulse sequences used can be found elsewhere by the interested reader.6 7
CMR strengths and weaknesses
The main benefits of CMR in the assessment of AS are its unlimited windows, excellent endocardial definition and its multiparametric capability combined with tissue characterisation of the myocardium. This is why CMR is regarded as the gold-standard non-invasive technique for the assessment of LV volumes, mass and function, and is the most accurate and reproducible technique for their quantification.8 9 It has been validated against postmortem studies of both animal and human hearts.10 11 The accuracy of the technique and lack of ionising radiation make CMR the ideal technique for the monitoring of progressive changes in ventricular mass and volumes, as well as the aorta, and assessing the effect of interventions in clinical trials. It also allows flow quantification through the valve for calculation of velocities and regurgitant fraction.
However, there are some limitations that need to be acknowledged. Its temporal resolution is inferior to that of echocardiography, making it difficult to assess small structures such as vegetations. The through-plane spatial resolution is also poorer, depending on the slice thickness used, leading to partial-volume effects. The flow velocities are usually underestimated compared with echocardiography.12 13 There remain absolute and relative contraindications to CMR, particularly with regard to implanted devices, so not all patients can undergo CMR. Access to CMR is another problem, with regional variation limiting its widespread application in clinical practice. Finally, the cost remains relatively high.
Assessment of the valve Morphology
CMR allows visualisation of aortic valve in multiple planes (figure 2), including the standard three-chamber and coronal long-axis views, which are then used to plan a series of short-axis views perpendicularly, with direct visualisation of the aortic valve orifice for morphology and planimetry. Establishing the morphology of the valve into tricuspid or bicuspid subtypes (figure 3) is important and not always possible with TTE. Patients with bicuspid aortic valves (BAVs) are known to have a greater degree of ascending aorta dilatation compared with tricuspid and out of proportion to the degree of valvular dysfunction,14 with some suggesting the largest dimensions in those with type-II BAV.15 Recently, time-resolved three-dimensional phase-contrast (PC) CMR, also called four-dimensional (4D) flow, has demonstrated different flow patterns between the BAV subtypes.16 There is also a greater incidence of coarctation of the aorta with BAV.
Imaging of the aortic valve. Multiple parallel short-axis slices are planned using the three-chamber and coronal LVOT views, to allow planimetry of the smallest aortic valve area.
Morphology of aortic valve: (A) tricuspid, (B) bicuspid type-I (fusion of right and left coronary cusps), (C) bicuspid type-II (fusion of right and non-coronary cusps), (D) bicuspid type-III (fusion of left and non-coronary cusps). LCC, left coronary cusp; NCC, non-coronary cusp; RCC, right coronary cusp.
Severity
CMR can be a particularly useful non-invasive tool for AS severity assessment in those with poor transthoracic windows, or those with borderline severity values on echocardiography. Accurate assessment of AS severity on echocardiography is reliant on appropriate alignment of the Doppler with the valve, which can be difficult in some cases. Accurate LVOT diameter assessment is also a limiting factor in TTE, with both TOE and cross-sectional imaging (CT and MRI) confirming a more elliptical shape than the circular assumption used in derivation of the LVOT area for continuity aortic valve area (AVA) calculation, leading to underestimation of stroke volume and AVA by TTE.17–19 In addition, it is now recognised that LVOT diameter should be measured at the base of the aortic valve cusps, rather than 1 cm below it, as previously recommended, partially due to the LVOT being more muscular and elliptical in shape below the annulus.20
Planimetry AVA
Planimetry of AVA by CMR has very good agreement with TOE.21 The planimetry should be performed at the valve tips, for the minimal area, for which multiple parallel thin slices (4–5 mm) with no slice gap, or even overlapping slices, can be acquired. The balanced steady-state free precession imaging is the standard pulse sequence used for cine imaging, though gradient echo pulse sequence can be used if significant turbulent flow artefacts are present and routinely at 3T. It is important to point out, however, that anatomical AVA and the calculated effective orifice area (EOA) using continuity equation are not the same measurement, as EOA represents the mean area in systole and can be influenced by flow convergence downstream of the anatomical area, whereas, the planimetry AVA represents the maximum instantaneous valve area in systole. The thresholds for severity are therefore higher for planimetry, as demonstrated using CT AVA.22
Phase-contrast imaging
PC velocity mapping is used to visualise and quantify blood flow through the stenotic valve. This technique uses the differences in the ‘phase’ or the angular position of a proton’s spinning vector, between static tissue and moving blood. This is achieved by the application of a pair of gradients of equal strength but in opposite direction, with the phase difference induced by the first gradient in the static tissue being completely reversed by the second gradient, leading to a net phase of zero.23 However, the protons in the flowing blood move along the gradient and experience a different gradient, with a net phase, that is not zero, and is proportional to the velocity of the moving blood. This is the principle used to derive a flow velocity map, with each pixel velocity displayed on a grey scale. A region of interest is drawn on each frame of the cardiac cycle, and the flow volume is calculated by multiplying the velocity within each pixel by the area. PC-imaging can be done in both in-plane, with visualisation of the maximal flow and then through-plane in the short-axis plane, for quantification of the maximal flow velocity (figure 4). However, as mentioned earlier, CMR flow velocities can be underestimated compared with echocardiography, especially at higher velocities,12 due to the temporal resolution being around 25–45 ms, compared with ~2 ms for continuous wave Doppler echocardiography,23 the presence of turbulent flow artefacts and partial-volume effects. In addition, there are fundamental differences between the two techniques: CMR measures voxel averaged velocities reflecting a mean of the voxel with the fastest velocity, compared with instantaneous peak velocities measured on TTE, further adding to the lower values obtained on CMR.
Through-plane phase-contrast velocity imaging of the aortic valve, with magnitude (anatomical) and phase (velocity) image on the left, used to produce a peak velocity against time curve (peak velocity 5.8 m/s) and flow curve for calculation of regurgitant volumes.
Hybrid EOA calculation
Various hybrid measures can be used to calculate the EOA by substituting different parts of the continuity equation with cross-sectional imaging based values and combining it with Doppler data from TTE. CMR and CT can be used to image the LVOT for direct measurement of LVOT area, and stroke volume can also be calculated from either LV volumetric analysis (end-diastolic volume and end-systolic volume), or forward flow measured on PC-velocity mapping in the ascending aorta. One study using hybrid CMR EOA (CMR-derived stroke volume with TTE-Doppler) resulted in a 48% reduction in discordant severity.19 On the other hand, a CT study showed larger CT-measured LVOT derived hybrid EOA but no better correlation with mean gradients or outcome in severe AS.22
Assessment of the myocardium
Patterns of remodelling
CMR provides accurate assessment of LV volumes, mass and ejection fraction (figure 5), and has provided a better understanding of the remodelling response of the LV to the pressure overload caused by AS. There is known variation in the remodelling response for a similar degree of AS, and CMR has played a key role in identifying different patterns, ranging from concentric remodelling to eccentric hypertrophy, prior to dilatation and decompensation.24 CMR has also provided important insights into the gender differences in the remodelling response, with men demonstrating higher indexed LV volumes and mass, more concentric remodelling (higher LV mass/volume), more late gadolinium enhancement (LGE), with worse systolic and diastolic function than female patients with a similar degree of AS.25 26
Assessment of left ventricular volume, mass and ejection fraction on CMR. Long-axis four-chamber and two-chamber views are used to plan multiple parallel slices every 10 mm, perpendicular to the interventricular septum, to produce a short-axis stack of cine images. CMR, cardiac magnetic resonance.
Late gadolinium enhancement
A major strength of CMR is tissue characterisation (figure 6). Fibrosis is a key determinant of both diastolic and systolic LV dysfunction in AS. LGE imaging following administration of gadolinium-based contrast agent, allows visualisation and quantification of focal areas of fibrosis, including infarct pattern and non-infarct midwall fibrosis. It has been validated in necropsy studies in hypertrophic cardiomyopathy27 and surgical biopsy studies in AS.28 29 LGE can be detected in 27%–64% of patients with AS.28 30 31 The extent of LGE has been shown to correlate with the extent of interstitial fibrosis on endomyocardial biopsy28 and increases with increasing LVH.30 31 LGE is also inversely associated with the degree of functional improvement post AVR32 and all-cause mortality late after AVR.4 28 In a recent large multicentre study of 674 patients with severe AS who underwent SAVR or TAVR, fibrosis detected on LGE was present in half the patients and was an independent predictor of mortality post-intervention.33 LGE can also be useful in the detection of myocardial infarction and viability in someone with LV dysfunction or known coronary artery disease, prior to intervention. Randomised trials are needed to determine whether the use of imaging biomarkers of fibrosis can be used to improve outcome in asymptomatic patients with AS. One such trial that has recently commenced is Early Valve Replacement Guided by Biomarkers of LV Decompensation in Asymptomatic Patients with Severe AS (EVOLVED-AS); NCT03094143, which randomises patients with CMR-detected fibrosis to surgery versus a watchful waiting approach.
Multiparametric assessment of the myocardium by CMR. (A) ES and (B) ED frame from short-axis cine with left ventricular endocardial (red) and epicardial (green) contours shown, used for calculation of ejection fraction and mass. (C) Precontrast and (D) postcontrast T1 map used for calculation of extracellular volume fraction, a surrogate for diffuse interstitial fibrosis. (E) First-pass stress perfusion imaging showing a global subendocardial perfusion defect (seen as dark areas marked by the arrows). (F) Late-gadolinium enhancement image showing non-infarct pattern mid-wall fibrosis (seen as white patches marked with the arrows). ED, end-diastolic; ES, end-sytolic; CMR, cardiac magnetic resonance.
T1 mapping
As LGE only detects focal areas of focal scarring, this technique cannot quantify interstitial/diffuse fibrosis. Interstitial fibrosis is associated with increased collagen content and increased myocardial extracellular volume fraction (ECV). T1 mapping directly measures the T1 relaxation time of the myocardium, and used pre-contrast and post-contrast administration, with knowledge of the haematocrit (as contrast is only distributed extracellularly), allows calculation of ECV, which is a surrogate of diffuse interstitial fibrosis.34 Native T1 values have been shown to be higher in patients with severe symptomatic AS compared with controls and are moderately correlated with fibrosis on histology.35 However, no differences in either T1 or ECV were found between asymptomatic patients with moderate to severe AS and age-matched controls, suggesting its limited role in assessing individual patients.36 ECV is more than just a measure of diffuse interstitial fibrosis, as it measures all the extracellular space, including the normal matrix supporting myocytes as well as intramyocardial blood vessels,37 and therefore can be confounded by other parameters. However, recent CMR studies have used it to calculate the absolute cellular and extracellular volumes (also known as indexed ECV), which has been correlated with histological diffuse myocardial fibrosis,38 and been used to track LV mass regression post-AVR, which comprises a combination of cellular and matrix volume reduction, with a greater degree of cellular regression, and no change in focal fibrosis (LGE).39 It, therefore, holds promise as an important imaging marker of disease progression in AS, and may provide an ideal tool in the future in timing of intervention and as endpoints in therapeutic trials of antifibrotic agents.
Myocardial perfusion
Myocardial blood flow (MBF) can be visually and quantitatively assessed on CMR using first-pass perfusion imaging of contrast agent injected after vasodilator stress (using adenosine or regadenason), ionotropic stress (dobutamine) or exercise. This can be used to exclude coronary territory ischaemia prior to valve intervention, in combination with LGE to assess myocardial viability. This can be particularly useful in identifying the aetiology of symptoms in those with moderate or borderline severe AS, who may have underlying coronary artery disease. In addition, it can demonstrate global subendocardial perfusion defects commonly seen in the hypertrophied myocardium, which represents microvascular dysfunction/insufficiency which contributes to the development of angina even in patients with non-obstructed coronary arteries40 (figure 7).
Utility of first-pass perfusion imaging after adenosine stress in aortic stenosis. Both patients had asymptomatic severe aortic stenosis: Patient-A had evidence of coronary artery disease, with inferior/inferoseptal perfusion defect, consistent with right coronary artery disease. Patient-B had global subendocardial perfusion defect most likely due to microvascular dysfunction.
Myocardial perfusion reserve (MPR) is the ability of the myocardium to increase its blood flow on stress and is calculated as the ratio of MBF during hyperaemia to resting MBF. In the absence of significant epicardial coronary artery disease, a reduction in MPR suggests the presence of microvascular dysfunction,41 which occurs because of the increased metabolic demands of the hypertrophied myocardium, with a relatively reduced capillary density and increased vasodilation at rest to maintain rest perfusion. CMR measured MPR has been shown to be an independent predictor of exercise capacity (peak oxygen consumption) in severe AS,42 as well as a predictor of symptom onset in asymptomatic AS.43 Although qualitative perfusion imaging is widely used in coronary artery disease assessment, its quantification has been limited by complex postprocessing and MBF analysis. However, more recent automated quantification techniques producing absolute MBF maps may make this technique more accessible, with wider application in valve disease in the future.44 45
Assessment of concomitant aortopathy
As mentioned above, BAV can be associated with an increased incidence of aortic root dilatation46 and vascular complications, with the reported incidence of aortic dissection being as high as 4%.47 CMR allows accurate assessment of the aortic root, arch and aorta and can provide a non-radiating imaging tool for consistent serial aortic assessment, as per ESC guidelines recommendations.5 Other congenital abnormalities such as coarctation of the aorta can also be readily diagnosed and monitored.
CMR has also provided insights into the mechanisms involved in the development of aortopathy and can provide non-invasive measures of aortic stiffness (distensibility and pulse wave velocity), as well as a more detailed assessment of flow patterns and wall shear stress using 4D flow imaging. This technique has demonstrated differences in systolic flow patterns between bicuspid and tricuspid valves,48 and the BAV subtypes,49 with right-handed helical flow and right-anterior flow jets in type-I BAV and left-handed helical flow with left-posterior flow jets in type-II BAV.16
TAVR
With an ageing population, TAVR is increasingly offering intervention to those who would have previously been managed medically. Imaging is key in preprocedural planning for appropriate prosthesis sizing, as well as access planning. CMR can be an alternative imaging tool for accurate assessment of the aortic annulus, especially in those with an allergy to iodine-based contrast agents used in CT or severe renal impairment precluding the use of contrast agents,50 and has been shown to have reproducible and similar results as CT.51 52
CMR can also play an important role in post-TAVI assessment, for accurate quantification of paravalvular regurgitation,53 an important prognostic marker post-TAVR, especially in patient with uncertain severity at TTE and persistent/recurrent heart failure symptoms. It has also been used to quantify reverse-remodelling following intervention.54
Summary/conclusions
CMR provides a non-invasive one-stop assessment tool of the aortic valve, myocardium and the aorta, in comprehensive assessment of patients with AS without exposure to ionising radiation. It can be particularly useful in those with poor echo windows, for clarification of stenosis severity when there are discrepancies on standard assessment, for additional information on myocardial viability and tissue characterisation and concomitant aortopathy. This ever-expanding imaging modality may also play an important role in future risk-stratification and timing intervention in patients with AS.
Key messages
While transthoracic echocardiography remains the mainstay imaging tool for assessment of aortic stenosis (AS), cardiac magnetic resonance (CMR) can provide complimentary information, particularly in difficult or borderline cases.
CMR provides a non-invasive, comprehensive assessment of the valve, the myocardium and the aorta.
The strengths of CMR include its unlimited windows, excellent endocardial definition and its multiparametric capability combined with tissue characterisation of the myocardium.
CMR is an ideal tool for research and serial monitoring, and has provided important insights into the pathophysiology of disease progression and myocardial remodelling in response to AS.
CMR can be an alternative imaging tool in pre-TAVI assessment, especially in those with a contraindication to iodine-based contrast agents.
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References
Footnotes
Contributors Both authors wrote the attached manuscript together and gave final approval.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Commissioned; externally peer reviewed.