The Dilemma of CAD in TAVR Candidates: Useful to Find It, Useless to Treat It?

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Until 20 years ago, when Alain Cribier revolutionized the treatment of valvular heart diseases, surgical aortic valve replacement and coronary artery bypass grafting represented the standard of care for patients with severe aortic stenosis and concomitant coronary artery disease (CAD) assessed by invasive coronary angiography. The management of CAD in the era of transcatheter aortic valve replacement (TAVR) is way more controversial, largely because of the evolving characteristics of TAVR candidates, which have rapidly shifted from excessively high-risk to lower-risk profiles, rendering complex the definition of standardized treatment strategies.

 

Current guidelines recommend to assess CAD before TAVR, either with invasive coronary angiography or coronary computed tomography angiography. However, the prognostic implications of CAD in this setting are unclear. A synthesis of available observational evidence was performed by 2 meta-analyses, published almost simultaneously, that evaluated the impact of CAD on mortality in patients undergoing TAVR with opposite results. Attempts to incorporate anatomical CAD complexity into a predictive model have also failed to provide conclusive evidence. Although 2 multicenter registries observed a consistent association of high baseline SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery) scores (SS) (>22) with adverse clinical outcomes at mid-term follow-up, CAD severity had no impact on clinical outcomes at 1 year in a largescale North American cohort.

 

The usefulness of revascularizing TAVR candidates looks even more debatable. Guidelines’ recommendation to consider percutaneous coronary intervention (PCI) before TAVR in case of angiographically significant stenoses of proximal vessels is based on expert consensus (eg, Level of Evidence: C).2,3 A meta-analysis of retrospective studies suggested that routine PCI before TAVR confers no benefits, and raised the concern of potential harm with higher rates of major vascular complications and short-term mortality. The recent ACTIVATION (PercutAneous Coronary inTervention prIor to transcatheter aortic VAlve implantaTION) trial—the first randomized trial testing noninferiority of PCI compared with conservative management in patients with CAD candidate to TAVR—largely confirmed previous observations, reporting similar rates of death and rehospitalizations at 1 year between the 2 groups and more bleeding in the PCI arm. Completeness of revascularization, as expressed through the residual SS (rSS), has been proposed as a prognostic marker, but again with conflicting results.

 

In this issue of JACC: Cardiovascular Interventions, Minten et al report the results of a prospective observational study, designed to evaluate the impact of the presence of CAD, complexity of CAD, angiography-guided PCI, and completeness of revascularization on short- and long-term outcomes after TAVR. The study included all-comers patients undergoing TAVR at a single center between 2008 and 2020, and CAD was defined by ≥1 coronary stenosis ≥50% at invasive coronary angiography. Although no significant differences were observed at 1- and 2-year follow-up, patients with CAD had significantly worse all-cause death (55.1% vs 67.9%; HR: 1.41; P = 0.022) and cardiovascular death (74.9% vs 84.9%; HR: 1.62; P = 0.039) as compared with those without CAD at 5-year follow-up. Similarly, higher SS were progressively associated with higher rates of all-cause (SS = 0: 32.1% vs SS = 1-22: 43.9%, vs SS >22: 47.0%; P = 0.027) and cardiovascular death (SS = 0: 15.1% vs SS = 1-22: 24.0%, vs SS >22: 27.8%; P = 0.024) at 5 years. Notwithstanding, both PCI and completeness of revascularization had no impact on mortality among patients with CAD.

 

This is, to date, the largest long-term follow-up study in the field. Of note, if the follow-up had been interrupted at 1 or 2 years, the study would have failed to detect any meaningful differences, because the impact of CAD presence and severity emerged beyond the first year of follow-up. Some previous studies might have, therefore, underestimated the prognostic effect of CAD in patients undergoing TAVR, highlighting the need for long-term follow-up to fully elucidate the relevance of CAD in this setting. Unfortunately, the investigators initially designed their study with a 2-year follow-up and only later prolonged the observation in a minority of patients (251/604, ∼40%). This might have determined a selection bias, because the enrolment ranged from 2008 to 2020, and patients who received a complete follow-up likely had higher surgical risk and greater burden of comorbidities than those enrolled in a more contemporary phase of the study. Additional limitations include the single-center design and the retrospective assessment of SS in an unblinded fashion.

 

The negative message of the study by Minten et al  is that, despite concomitant severe CAD is associated with impaired prognosis after TAVR, preventive PCI is ineffective to eliminate this underlying risk. A worrisome trend toward a higher risk of cardiovascular mortality across patients with more complete anatomical revascularization was observed (rSS 0-7: 27.6% vs rSS ≥ 8: 15.4%; P = 0.361). As expected from a real-world registry, physiological assessment of lesion severity was not routinely performed. A systematic implementation of physiology-guided PCI might represent an opportunity to optimize the management of CAD in TAVR candidates, because it has been shown to reduce adverse cardiovascular events as compared with angiography-guided PCI in a retrospective cohort of patients undergoing TAVR. However, the efficacy of physiological assessment before TAVR has not yet been tested in randomized trials, and several open issues exist. Firstly, the blunted response to adenosine related to severe aortic stenosis and left ventricular hypertrophy might lead to an overestimation of fractional flow reserve values, suggesting that phase-specific nonhyperemic indexes should be preferred in this setting. Secondly, there are controversies about the efficacy of physiology-guided PCI in patients with multivessel CAD  in whom a surgical treatment with concomitant coronary artery bypass grafting and surgical aortic valve replacement might still represent the treatment of choice.

 

Putting the findings of Minten et al  into context, CAD extent and functional significance should be evaluated together with patients’ clinical and anatomical characteristics to guide the management of CAD prior to TAVR (Figure 1). PCI could be reasonably deferred in patients with multiple comorbidities and at high bleeding risk, whereas pre-TAVR coronary revascularization should at least be considered if proximal segments of major epicardial arteries are diseased or if a challenging coronary reaccess is expected based on the aortic root morphology.

 

Proposed Guidance for CAD Assessment and PCI in TAVR Candidates

 

CAD = coronary artery disease; CV = cardiovascular; FFR = fractional flow reserve; iFR = instantaneous wave-free ratio; PCI = percutaneous coronary intervention; STJ = sinotubular junction; SYNTAX = Synergy between PCI with Taxus and Cardiac Surgery; TAVR = transcatheter aortic valve replacement; ViV = valve-in-valve.

 

Overall, CAD assessment before TAVR is pivotal to optimize risk stratification, but the treatment effects associated with preventive revascularization are likely to be heterogeneous and depending on appropriate patient selection.

 

 

 

 

This article is reproduced from JACC journals.

 

 

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