Transcatheter aortic valve implantation (TAVI) has moved into the cardiology mainstream with rapid acceptance of this new technology since the first implant in 2002 . The two devices with the largest experiences are the self-expanding CoreValve Revalving™ system (Medtronic CoreValve, Luxembourg) and the balloon expandable Edwards Sapien XT valve (Edwards Lifesciences, Irvine, CA). Both are employed in patients whose peri-operative risk is deemed too high for surgical aortic valve replacement (sAVR). Coronary artery disease has a high prevalence in these patients [2–5] and shares many of the same causative factors . While the matrices for these devices state that significant coronary artery disease (CAD) should preferably be treated prior to implantation, current practice is frequently not to do so. Indeed, successful PCI has been demonstrated post-implantation [7–9], as both technologies allow access to the coronary ostia. The presence of concomitant CAD has been associated with adverse procedural outcomes in sAVR [10, 11] and now also in TAVI . In this higher risk cohort, with a mean age in excess of the ‘normal’ population with chronic stable angina, we must carefully evaluate any coronary artery lesion’s significance in terms of the possibly greater risks of PCI and the impact on the planned valvular intervention.
Considerations in pre-transcatheter aortic valve implantation percutaneous coronary intervention
Among the possible advantages of revascularization prior to TAVI may be a protective effect against the ischemic burden of the procedure, including as it does periods of hypotension. The absence of contractile reserve is associated with increased mortality after sAVR , and significant stenoses not intervened upon could contribute to this. Surgical revascularization for multi-vessel coronary artery disease has been found to be an independent factor predictive of improvement of left ventricular ejection fraction (LVEF) after sAVR , and similar benefits for revascularization by PCI may exist. Improving coronary flow in symptomatic patients with significant flow-limiting stenoses may maximize this beyond the valvular intervention. Wave intensity analysis of coronary flow has demonstrated marked reduction in the diastolic suction wave in aortic stenosis (the dominant wave in coronary perfusion ), which significant stenosis may impair further .
The risks of PCI are well described: death, myocardial infarction, coronary artery bypass grafting (CABG), stroke, vascular access complications, renal insufficiency, allergy and stroke/TIA [16, 17]. PCI is also associated with an incidence of stent thrombosis of up to 1% with significant mortality [18, 19]. The presence of severe aortic stenosis could have a detrimental effect upon the ability to withstand these. Indeed, the hypotension experienced by patients during the TAVI procedure (especially during rapid right ventricular pacing) may actually increase the risk of stent thrombosis. There has been increasing recognition recently of the adverse outcomes associated with major bleeding post-PCI [20, 21]. Current opinion is to continue aspirin for life and clopidogrel for one month after bare metal stenting and 12 months after insertion of a drug-eluting stent. This would possibly impact upon bleeding complications in transfemoral, subclavian and transaortic TAVI and would certainly be of concern in patients undergoing TAVI via the transapical approach, given the direct myocardial access required. Angiography in the 24 hours, or even the 5 days, prior to sAVR has been shown to be associated with acute kidney injury post-operatively . These risks may also exist if PCI and TAVI are inadequately separated or combined in a hybrid procedure. Finally, patients would require two admissions with attendant implications to cost and risk. This latter consideration might be offset against the possible reduction in length of stay in the post-TAVI period.
Why do we need a randomized trial?
The data on coronary artery disease in TAVI and PCI in this context is certainly provocative, but there are several major limitations, given that the studies are all nonrandomized, registry-type with relatively small sample sizes.
The lack of data on pre-procedural revascularization has led to some variability between centers on the level of coronary interventions undertaken prior to implantation. A retrospective analysis by Masson et al. stratified TAVI patients according to myocardium at risk due to coronary artery disease, finding no difference in 30-day or 1-year mortality between the groups . However the small group sizes involved would have required a mortality difference between even the two most extreme groups at 30 days of greater than one third to gain significance, limiting our use of this data. The access approach used was not included in their risk model, an important omission given the known differences in risk profiles between, for example, TF-TAVI and TA-TAVI cohorts. In the German TAVI registry, CAD was defined as previous revascularization (either PCI or CABG) OR a stenosis of ≥50% and was noted in 62% of 1,382 patients. These patients had a greater in-hospital mortality (10.0 versus 5.5%, P <0.01), required more frequent cardio-pulmonary resuscitation (7.8 versus 3.5%, P <0.01) and suffered greater 30-day mortality (log rank P = 0.041). But there were significant differences in the group demographics: more frequent peripheral vascular disease, lower left ventricular (LV) ejection fraction and higher logistic EuroScores in patients with CAD . The Italian CoreValve registry noted that in patients with critical ostial disease, myocardial infarction (MI) within 12 months of TAVI was greater in those patients who were not revascularized prior to TAVI . A recent meta-analysis of the effects of CAD upon outcome in the midterm showed no effect; but again, of seven included studies, five defined CAD as previous revascularization, and the remaining two used 50% stenosis severity .
The presence of pre-existing treated coronary artery disease has been identified as an adverse risk factor for procedural and long term outcome . With regards to the effects of pre-TAVI PCI, Masson and colleagues performed a sub-analysis of just 15 patients in whom PCI was performed at the discretion of the individual cardiologist: the resultant selection bias in turn clouds the interpretation of any findings. The mortality in the overall group one-year after TAVI was reported as 77.9% and was found to be 80% in those with pre-emptive PCI - though no comparison between the two cohorts was performed . Abdel Wahab et al. reported that 55 patients who underwent PCI prior to TAVI showed no difference in adverse events at either 30 days (2% versus 6%; P = 0.27) or 6 months (9% versus 14%; P = 0.42) when compared to a group undergoing isolated TAVI . The feasibility of PCI for CAD in patients with severe AS has been demonstrated by Goel et al. in a cohort of 258 patients over a 10-year period with a favorable comparison with propensity matched patients without the aortic disease .
There has been a rapid, global expansion in the use of TAVI to treat aortic stenosis in patients who are not candidates for sAVR. The efficacy of this technique has been successfully demonstrated in randomized, controlled trials [28, 29] and in large registries [30, 31], and there is now a need to improve patient safety and outcome, including how to manage patients with concomitant CAD. Given the paucity of data on the issue and variation in practice and recommendations we feel a randomized controlled trial (RCT) is essential for safe evidence-based practice. ACTIVATION is the first randomized controlled trial of elective PCI prior to TAVI. Its findings will help define the optimum revascularization strategy in this procedure and help create evidence-based guidelines on this controversial issue.