Discussion
This large observational study was designed to examine the association of concomitant CAD on mortality and readmission outcomes in patients who underwent a TAVI procedure. This all-comer study included patients over a 7-year period with a 3-year follow-up and therefore is representative of daily practice within a tertiary cardiology centre. From the analysis, there is no correlation between concomitant CAD at the time of TAVI with either mortality or readmission of patients following their procedure in a centre in which it is common practice not to routinely revascularise concomitant CAD. Furthermore, the presence of left main CAD and multivessel disease were also not correlated with these outcomes.
This finding is consistent with the evidence for stable CAD revascularisation outside of the context of severe AS, where there has not been a demonstrable mortality benefit.12 13 However, most contemporary guidance advocate revascularisation for LMS or multivessel disease in chronic stable angina on both symptomatic and prognostic grounds.14 The finding that this pattern of CAD does not have an effect on mortality over a 3-year follow-up period in our study might reflect frailty and multimorbidity in this patient group; something which may not necessarily be reflected in the trials of intervention in chronic stable angina. Furthermore, it is important to note that even for treated severe AS, mortality at 1 year was approximately 20% in this cohort. This may ‘drown out’ any differences in mortality related to CAD. This study did not examine the cause of death which might have demonstrated differential cardiovascular outcomes, but we postulate that absolute differences would be small.
In addition to the mortality benefits in severe AS, TAVI also serves as an effective treatment of symptoms with significant reductions in NYHA class of breathlessness.15 In this cohort, there were significant reductions in both CCS angina and NYHA breathlessness scores after TAVI which were independent of the presence of concomitant CAD. This suggests that the resolution of aortic valve pathology is the main driver of symptom improvement in this cohort rather than coexisting CAD.
Coexisting CAD was also demonstrated not to be correlated significantly with all-cause readmissions following TAVI. Readmission is an important clinical outcome in this cohort that tends to be multimorbid and frail. Arguably, readmissions are of as much significance to patients as any mortality benefits from TAVI. The Kaplan-Meier curves for readmission diverge at 18 months of follow-up with a numerically higher number of patients being readmitted who had concomitant CAD. The Kaplan-Meier survival curves diverge earlier when restricted to those readmissions for a composite cardiovascular endpoint including MI, but still not statistically significant. Of those patients readmitted with ACS, only limited numbers were treated by PCI and the remainder were managed medically. This result should be interpreted in the context of bias as it requires accurate coding and the knowledge of pre-existing coronary disease may bias a physician’s decision to admit, treat and ultimately code a readmission as an ACS.
Some argue that angioplasty after the fact is rendered more difficult with a TAVI prosthesis and therefore would support revascularisation for severe lesions on a prophylactic basis. However, our data suggest otherwise. Firstly, only a very small proportion of patients re-present with an ACS following a TAVI. Secondly, our data have shown that of those who had PCI for ACS after TAVI, only one patient had the culprit lesion identified on the pre-TAVI angiogram. This suggests that the presence of CAD on angiography is a general marker of risk in this cohort rather than a robust mechanism by which to identify future culprit coronary lesions.
The most important limitation of this study is that it is observational and is prone to the pitfalls associated with non-randomised data, such as inclusion, interpretation bias and unmeasured confounding. In addition, this registry employed a 50% angiographic stenosis, to be deemed a significant coronary artery lesion. This is an arbitrary cut-off based on a visual angiographic assessment in two or more orthogonal views. It does not account for functional impact of these lesions with physiological indices such as FFR/iFR. It also does not account for description of plaque morphology by intracoronary imaging both of which are potential predictors of future cardiovascular events.16 Having said this, physiological indices are difficult to interpret in the context of severe AS, with different thresholds suggested.17 Our findings are contrasted with other registry data in which concomitant CAD was associated with worse outcomes at 5 years of follow-up.18 This was particularly true of those with more complex CAD (Syntax score >22). However, even though up to 30% of patients underwent pre-TAVI PCI, there was no effect on outcomes. Furthermore, at 3 years of follow-up, there were no significant differences in all-cause mortality in patients with and without CAD.
While the pitfalls of observational data are evident, RCTs for this cohort of patients have proved difficult to recruit to. The largest RCT, ACTIVATION,11 failed to recruit a sufficient number of patients. The NOTION 3 study is currently running and will randomise patients with severe AS selected for TAVI and at least one coronary lesion of >90% stenosis or with an FFR <0.8.19 Again, questions will remain about the validity of physiology in this cohort, in addition to the difficulty in recruiting patients, as the authors of ACTIVATION found.
This large observational study demonstrates no association between concomitant CAD on either mortality or readmissions following TAVI. It suggests that having a strategy whereby coronary lesions are not routinely revascularised around the time of TAVI is generally safe. With the difficulty in performing RCTs in this area, it may be that findings from large cohorts, such as this, are sufficient to inform our practice of how to manage CAD in patients undergoing TAVI.