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Page 2 of 13 Cangemi et al. Mini-invasive Surg 2022;6:3 https://dx.doi.org/10.20517/2574-1225.2021.99

[2]
and 86 of age have a moderate to severe form . There is evidence that risk factors for aortic stenosis are
[2,3]
similar to those for atherosclerotic disease . Consequently, coronary artery disease (CAD) is often
concurrently found in patients presenting with severe AS, and its incidence increases with the age . Surgical
[4]
aortic valve replacement (SAVR) was the first treatment to increase survival in patients with severe aortic
stenosis and was the only one for decades. Transcatheter aortic valve implantation (TAVI) has
revolutionized the treatment of severe aortic stenosis, allowing many high-risk patients to receive a
treatment, which increases life expectancy. The prevalence of CAD in TAVI candidates is estimated to be
[5]
around 40%-75% . In randomized clinical trials comparing TAVI to SAVR, there was a progressive
reduction in the prevalence of CAD in TAVI candidates in parallel with lower surgical risk and younger
age [6-11] . With the progressive reduction of age and surgical risk of patients who are candidates for TAVI,
optimal management of concomitant coronary artery disease becomes crucial. Important unresolved
questions are if, how, and when to treat coexisting coronary artery disease.

PROGNOSTIC IMPACT OF CORONARY ARTERY DISEASE IN PATIENTS WITH AORTIC
STENOSIS CANDIDATES FOR TREATMENT
It is still unknown whether CAD can be considered a detrimental factor or just an innocent bystander
marker of high risk. This is probably due to the heterogeneity of the definition of CAD and its composite
endpoints, the small sample size, the limited use of physiological assessment through fractional flow reserve
(FFR), the uncertain completeness of revascularization or coronary stenosis severity, and the limited follow-
up duration of studies [Supplementary Table 1]. One of the main limitations of these studies is that they do
not correctly differentiate patients for severity of coronary artery disease and different types of
revascularization. Severity of CAD and its presentation could better stratify patient prognosis. In support of
this thesis, other features have been variably associated with prognosis: a clinical presentation with acute
coronary syndrome (ACS) , CAD severity , and incomplete revascularization with a high residual
[13]
[12]
SYNTAX SCORE . Moreover, in a single-center Polish registry, the presence of chronic total occlusion
[13]
was associated with higher all-cause mortality rate in patients undergoing TAVI, but these patients had a
[14]
more frequent history of stroke and chronic obstructive pulmonary disease . Different meta-analyses on
this topic showed conflicting results regarding the association between CAD and clinical outcomes post-
TAVR [15-17] .

TREATMENT OF CORONARY ARTERY DISEASE IN PATIENTS WITH AORTIC STENOSIS
CANDIDATES FOR TREATMENT
The main question to be answered in each TAVI procedural planning is whether patients with established
CAD should undergo coronary revascularization. Several observational and retrospective studies comparing
TAVI vs. TAVI and percutaneous coronary intervention (PCI) in patients with CAD did not find a
significant difference in terms of mortality [Supplementary Table 2]. This lack of evidence could also be
related to the reasons mentioned above. Another limitation of these retrospective studies is the selection
bias of candidates for revascularization: patients with more severe CAD are revascularized, while those with
stenosis in distal vessels tend to be treated with medical therapy. In several studies, the presence of CAD
[18]
increased the procedural risk of SAVR . Moreover, a higher mortality was found in concomitant coronary
artery bypass graft (CABG) + SAVR than in SAVR alone . In all randomized trials [6-11] comparing TAVI to
[19]
SAVR, PCI in addition to TAVI was less frequent compared to SAVR + CABG [Figure 1]. This trend
reflects the approach recommended by the current guidelines [20,21] that suggest revascularization of the
proximal coronary stenosis in TAVI candidates and recommend CABG in patients with a primary
indication for SAVR. These recommendations are based mainly on retrospective studies and registries data.
The ACTIVATION trial was the first randomized trial to compare routine PCI and medical treatment in
[22]
patients affected by severe AS and CAD undergoing to TAVI. This study showed no difference in the