Aortic stenosis and CT calcium scoring:is it for everyone?Timothy R G Cartlidge, Tania A Pawade, Marc R Dweck

The evaluation of aortic stenosis (AS)severity is routinely performed using echo-cardiography. Current guidelines recom-mend integrating data with respect to thepeak aortic valve jet velocity, the meantransvalvular gradient and the aortic valvearea (AVA) calculated by the continuityequation.1 For the majority of patients thisassessment works well. However in athird of subjects there is discrepancy in theresults provided by these different mea-sures.2 Most commonly this takes the formof an AVA <1.0 cm2 indicating severestenosis but a peak velocity <4 m/s andmean gradient (MG) <40 mm Hg consist-ent with moderate disease. While this cansometimes be explained by a low-flowstatus this is often not the case.3 Whatthen to do in that common situation?

Major interest now surrounds CTcalciumscoring of the valve as an assessment of ASseverity in cases where echocardiographicmeasurements are conflicting.4 This is ofparticular appeal because calcification isbelieved to be the predominant processdriving AS progression and because it pro-vides a flow-independent assessment ofseverity.5 Complex categorisation of pat-ients based upon flow status and systolicfunction is therefore not required.

The last few years have witnessed rapidadvances in this field. Aortic valve CTcalcium scoring has demonstrated a closeassociation with haemodynamic mea-sures of AS on Doppler echocardiographyand offers powerful prediction of futuredisease progression.2 6 Moreover we nowhave proposed cut-offs for differentiatingmoderate from severe disease (men2065 AU, women 1274 AU) that providepowerful prognostic information overand above standard echocardiographicindices.7 However, before CT calciumscoring translates into clinical practice it isimperative that we are able to interpret itsresults in all the different types of patientsaffected by the disease. For example it hasbecome evident that there are differencesin CT calcium scoring between the sexes

with women requiring less calcium thanmen to develop severe stenosis (even afterindexing for body size), perhaps reflectingthe hormonal effects of testosterone.8

The Heart manuscript by Shen et al9

expands on this important theme, investi-gating whether CT calcium scoring islikely to be of clinical use in patients withbicuspid valves and in younger patientswith AS. Two hundred patients with arange of stenosis severities were prospect-ively recruited as a subgroup of thePROGRESSA study. No patient in thecohort had a history of rheumatic feverand all had preserved left ventri-cular systolic function. They underwentDoppler echocardiography and CTcalcium scoring within a 3-month period,allowing comparisons to be made betweenthe assessments of disease severity on thetwo scans. In particular the authors inves-tigated the agreement between the meantransvalvular gradient on echocardiog-raphy and the aortic valve calcium density(AVCd) from CT. AVCd is a simple surro-gate of the aortic valve calcium score butindexes it to the cross-sectional area ofthe left ventricular outflow tract toaccount for different valve sizes. It mayoffer incremental diagnostic accuracy indetermining AS severity using cut-offs ofAVCd 292 AU/cm2 in women and476 AU/cm2 in men.2

Twenty per cent of the cohort had abicuspid aortic valve and 80% a trileafletvalve. As expected the latter were older(median age 72 years vs 51 years), morelikely to be male (76% vs 56%) and hadmore comorbidities. In these patients withtrileaflet valves a good correlation wasobserved between increasing AVCd andMG (ρ=0.61, p<0.0001) that persisted inboth the younger (<72 years) and older(≥72 years) age groups. The storyhowever appeared different in the cohortof patients with a bicuspid aortic valve.While patients ≥51 years in this groupstill demonstrated a strong correlationbetween AVCd and MG (p=0.55,p=0.009) no correlation was observed inpatients aged <51 years with a bicuspidaortic valve.These observations have important

implications both with respect to theutility of CT calcium scoring and thelikely pathobiology underlying valve

narrowing. First, it suggests that CTcalcium scoring is likely to be of clinicalutility in the vast majority of patients thatwe encounter in the clinic: subjects withtrileaflet valves and patients >51 yearswith a bicuspid valve. Moreover it indi-cates that calcium is crucial to the patho-physiology of valve narrowing in thesepatients and therefore an importantpotential therapeutic target.5

However it also implies that CTcalcium scoring may grossly underesti-mate the severity of AS in young patientsunder 50 years with a bicuspid valve.This imaging technique should thereforebe approached with caution in this sub-group and probably avoided. What is thepathophysiological explanation for thisanomaly? Perhaps the first question toaddress is whether it predominantlyrepresents a function of the bicuspidstructure of the valve or of patient age(subjects in this group were substantiallyyounger than the patients in the trileafletgroup). The authors postulate severalexplanations related to the former: thatbicuspid valves may suffer from leafletfibrosis rather than calcification; thatabnormalities in the morphology of theleaflets and valve orifice lead to increasedgradients and reduced effective orificearea; or that the eccentric jets associatedwith bicuspid valves cause a pressuredrop in excess of the reduction in effect-ive orifice area. While each is plausible,why these factors would affect youngerpatients with bicuspid valve disease butnot older subjects remains unclear. Thealternative explanation is that this phe-nomenon instead simply reflects a func-tion of age. As discussed the patients notdemonstrating a correlation between MGand AVCd were substantially youngerthan the other subjects in the study. Thelack of calcium in the valves of thesepatients might therefore reflect a differentpathological process in those under theage of 50 years, who also appear lessprone to calcification in other conditions.

Further work in this area is required.Interestingly we recently encountered a58-year-old female patient that mightsupport this hypothesis. She had a trileaf-let aortic valve and no history of rheum-atic heart disease or hyperlipidaemia.Echocardiographic measurements were dis-crepant but suggested at least moderate AS(peak velocity 3.6 m/s, MG 27 mm Hg,AVA 0.8 cm2). However her CT calciumscore indicated only minimal calcification(36 AU, AVCd of 12.7 AU/cm2), appar-ently out of keeping with the degree ofher valve narrowing. A contrast CT wasperformed and provided explanation

Centre for Cardiovascular Science, University ofEdinburgh, Edinburgh, UK

Correspondence to Dr Marc R Dweck, Chancellor’sBuilding, University of Edinburgh, 49 Little FranceCrescent, Edinburgh EH16 4SB, UK; marc.dweck@ed.ac.uk, marcdweck@hotmail.com

Cartlidge TRG, et al. Heart Month 2016 Vol 0 No 0 1

Editorial Heart Online First, published on September 19, 2016 as 10.1136/heartjnl-2016-310297

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demonstrating extensive valve thickeningand narrowing, in the absence of calcifica-tion but with appearances consistent withfibrosis (figure 1). While anecdotal andlacking histological validation, this caseillustrates that young patients may developadvanced AS in the absence of majorvalve calcification and supports a differ-ence in their underlying pathobiology.Alternative imaging and therapeutic strat-egies may therefore be required in thesepatients compared with the broader popu-lation with AS.

In summary Shen et al are to be congra-tulated on their innovative study. Indeedthere is a need for more such studies toinform about which patients with ASwould benefit from CT imaging and toprovide further insights into the com-plex pathophysiology underlying thiscondition.

Funding TAP, TRGC and MRD are supported by theBritish Heart Foundation (SS/CH/09/002/26360, FS/13/77/30488, SS/CH/09/002/2636, FS/14/78/31020).MRD is the recipient of the Sir Jules Thorn Award forBiomedical Research 2015.

Competing interests None declared.

Provenance and peer review Commissioned;internally peer reviewed.

Open Access This is an Open Access articledistributed in accordance with the Creative CommonsAttribution Non Commercial (CC BY-NC 4.0) license,which permits others to distribute, remix, adapt, buildupon this work non-commercially, and license theirderivative works on different terms, provided theoriginal work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

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Figure 1 A 58-year-old woman with aortic stenosis investigated by echocardiography and CT. (A) Doppler echocardiography demonstrating a peakaortic valve (AV) velocity of 3.6 m/s, a mean gradient of 27 mm Hg and an aortic valve area (AVA) of 0.8 cm2 based upon the continuity equation.(B) Non-contrast calcium scoring CT in the axial plane showing minimal aortic valve calcification (AV calcium score 37 AU). (C) Images fromcontrast-enhanced CT in the en face plane and (D) coronal plane revealing marked leaflet thickening with low attenuation signal suggestive of valvefibrosis. AO, aorta; AV, aortic valve; AVA, aortic valve areas; PG, pressure gradient; VTI, velocity time integral.

2 Cartlidge TRG, et al. Heart Month 2016 Vol 0 No 0

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