Title : Systematic literature review of class 2 guidelines on timing and interventions for severe aortic stenosis
Abstract:
Background: Aortic stenosis (AS) is a progressive condition with high morbidity and mortality if left untreated. Currently, there are clinical guidelines to help provide physicians with recommendations for clinical decisions. Class 2 guidelines have inherently weaker evidence, but they are highly referenced and utilized daily. The purpose of this review is to examine the evidence and current research limitations behind the class 2 guidelines on timing and intervention for severe AS in order to identify areas where additional research is required.
Methods: A systematic review was conducted on class 2 guidelines on timing and intervention for severe AS using the 2020 ACC/AHA and 2021 ESC/EACTS guidelines. The literature used for these guidelines, published through December 2021, was analyzed to evaluate the type of evidence and limitations of these recommendations.
Results: The data utilized for these guidelines consisted of 1 RCT, 7 expert opinions, and 26 observational studies. Systemic review demonstrated that limitations to determine the ideal timing for AS intervention and which specific intervention include: difficulty to objectively and consistently determine symptom status solely due to AS (despite coronary artery disease (CAD) or deconditioning), user dependent nature of echocardiograms, utilization of arbitrary cut off values of biomarkers such as BNP, lack of comparison of between assays for ideal cut off value (e.g. BNP vs. NT-pro-BNP), utilization of speculative ideal left ventricular ejection fraction (LVEF) values for aortic valve replacement (AVR), unknown prevalence of CAD/myocardial strain/wall motion abnormalities, presence of wide range of AS disease severity within small studies, and lack of complete list of medications in some studies. Additionally, limitations include those inherent to observational studies, non-blinded RCTs, and small studies, as well as lack of data/trials for the 7 guidelines that are based on expert opinions.
Conclusion: The class 2 guidelines for AS interventions are largely based on observational data and expert opinion, indicating that clinical trials will upgrade the level of evidence on these topics. Further research is needed with a larger number of patients to increase external validity and include AS subsets. Additionally, further investigation is needed to assess prevalence/effect of CAD/ myocardial strain in AS and their effect on AS interventions, define the most useful biomarkers or combination of biomarkers and their optimum cutoff values for intervention. Additional data is also needed to determine the ideal cutoff of LVEF for AVR, as well as methodologies to objectively and consistently determine AS symptom status. Investigations should be initiated to support experts’ opinion such as specifics for consideration of non-transfemoral TAVI, balloon aortic valvotomy, and AVR while undergoing other cardiac surgery. Future studies, including RCTs where feasible, should address these gaps to upgrade guideline recommendations.
