Materials and methods

Search strategy

We conducted our study using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) investigation guidelines. We searched for all available articles that reported the survival rate in patients with LF LG AS following either AVR or no AVR9. A literature search was conducted in Embase and Medline databases through PubMed, as well as Google Scholar and Cochrane library. Moreover, we checked the relevant articles which are suggested on those databases as well as the references of the selected materials. We used both free text words and MeSH terms.
The search terms were “Therapy/Broad[filter]” AND “Aortic Valve Stenosis” OR “Aortic Valve Stenosis [MeSH Terms]” OR “Aortic Stenosis” OR “Aortic Stenosis [MeSH Terms]” AND “Low Flow” OR “Low-Flow” AND “Low Gradient” OR “Low-Gradient” AND “Aortic Valve Replacement” OR “Aortic Valve Replacement [MeSH Terms]” AND “Conservative Management” OR Conservative Management [MeSH Terms]” OR “Medical Treatment” OR “Medical Treatment [MeSH Terms]” AND “Surgical Intervention” OR “Surgical Intervention [MeSH Terms]” AND “Low-Flow Low-Gradient” OR Low Flow Low Gradient.”

Selection criteria

We included articles that met the following criteria: (a) performed on humans, (b) studies with more than 20 patients, (c) articles comparing AVR to noAVR procedures, (d) articles focused on LF LG AS, (e) studies published in English and (f) articles published within the last 15 years (2004 - 2019). On the other hand, we excluded articles with the following conditions: (a) performed on animals, (b) not in English, (c) case reports (d) literature reviews and meta-analyses, (e) population study of 20 or less, (f) articles that are older than 15 years, (g) studies not focusing on LFLGAS (h) studies which did not report a comparison between AVR and no AVR.

Methodological quality assessment

To assess the quality of the included studies, we used a modified tool of Down and Black’s Checklist for Measuring Quality10. This tool consists of 18 questions evaluating five criteria: (a) the overall quality of the study, (b) the external validity, (c) study bias, (d) confounding and selection bias, and (e) power of the study. Each question is graded on a binary basis (0 or 1) except for two items, ranked out of 2 and out of 5, respectively.
Two researchers (SA And LM) conducted the evaluation. A third researcher was involved in reviewing (OP). The agreement was quantified using Cohen’s kappa 11.

Endpoints

The primary endpoint of our study was the survival rate at follow up in patients with LFLG AS, treated with AVR or noAVR. Also, we aimed to investigate the impact of LVEF on survival. In the AVR group, we included both surgical valve replacement (SAVR) and transcatheter valve replacement (TAVR), while in the no AVR group, we included conservative medical management and valvuloplasty3.
LFLGAS was defined as an aortic valve area (AVA) of ≤1 cm2 or indexed AVA <0.6 cm2/m2, a stroke volume indexed (SVI) ≤ 35 mL/m2 and a transvalvular mean pressure gradient ≤ 40 mmHg. Preserved LVEF was identified as > 55% (paradoxical LFLGAS), while reduced LVEF was defined as < 50% (classical LFLGAS) 3.

Statistical analysis

This meta-analysis was conducted using V.3.6.1 (R Foundation for Statistical Computing, Vienna, Austria). We used Incidence Rate (IR) and proportions as main statistical indexes. Since the follow-up time was different in each article, we employed the IR test to analyze survival rates in both groups. Heterogeneity was evaluated by using the I-square test, and the publication bias was evaluated by using the Egger regression test. Furthermore, meta-regression was performed to evaluate the impact of LVEF on survival in both AVR and the noAVR group. We defined statistical significance for P values < 0.05.