Usefulness of aortic valve calcification in patients with low flow aortic stenosis

Background Aortic valve calcification (AVC) has been shown to be a powerful assessment of aortic stenosis severity (AS) and predictor of adverse outcome. However, its accuracy in patients with low-flow AS has not yet been proven. Objectives To assess the predictive value of AVC in patients classical (CLF, i.e. low left ventricular ejection fraction [LVEF]) or paradoxical (PLF, i.e. low flow preserved LVEF) AS patients. Methods We prospectively include 641 patients, 319 (49.8%) with CLF-AS and 322 (50.2%) with PLF-AS who underwent Doppler-echocardiography and multidetector computed tomography. AVCratio was calculated as AVC divided by the sex-specific AVC threshold for AS-severity; AVC score ≥2,000 AU in males, and ≥1,200 AU in females. The primary endpoint of the study was all-cause mortality regardless of treatment. Results During a median follow-up of 4.9 (4.3-5.9) years there were 265 deaths. After comprehensive adjustment, AVCratio was associated with all-cause mortality in CLF-AS (aHR=1.25 [1.01-1.56]; p<0.05) and PLF-AS (aHR=1.51[1.14-2.00]; p=0.004) patients. There was an interaction (p=0.001) between AVC and AS flow pattern (i.e. CLF vs. PLF) with regard to the prediction of mortality. The best AVCratio threshold to predict mortality was different in CLF-AS (AVCratio≥0.7) and PLF-AS (AVCratio≥1) patients. After comprehensive analysis, AVCratio as a dichotomic variable was associated with all-cause mortality in all groups (p≤0.001). The addition of AVCratio to the models improved all model’s predictive value (all net reclassification index >18%; all p≤0.05). Conclusion In patients with CLF or PLF AS, AVC is a major predictor of mortality. Thus, AVC should be used in low flow patients to stratify risk. Importantly, in patients with reduced LVEF, a non-severe AS (i.e. AVC 70% of severe) could be associated with reduce survival. Clinical Perspective What is new? What are the clinical implications? ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial Not a clinical trial ### Funding Statement This work was supported by research grants from Canadian Institutes for Health Research, the Institut de cardiologie et de Pneumologie de Québec, the Region of Southern Denmark and the University of Southern Denmark. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRB from Institut de cardiologie et de pneumologie de Québec and Odense university hospital. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data that support the findings of this study are available on request from the corresponding author, [MAC].