The Evolving Role of Percutaneous Intervention in Coronary Artery Disease with Coexistent Aortic Stenosis

Aortic stenosis (AS) and coronary artery disease (CAD) are both prevalent, with recent studies showing similar lesion histology, and also an association between traditional atherosclerotic risk factors and the development of AS.^1–3 The prevalence of calcific AS increases with age, affecting 2-3% of the population > 75 years of age.^2,4 Coexisting CAD (>= 70% diameter stenosis) is present in approximately 40% of patients with AS.5 Therefore, patients who require aortic valve replacement (AVR) for AS often undergo concomitant coronary artery bypass surgery (CABG). The key management dilemma for AS revolves around the optimal timing of AVR, with the need to balance the benefits of improving symptoms and survival, with the risks of perioperative and subsequent cumulative complications related to the prosthesis. Prosthesis-related complications are not trivial, occurring at roughly 2–3% per year, with a mortality rate of approximately 1% per year.⁶ The class 1 indications for AVR as recommended by the current ACC/AHA Task Force are: symptomatic patients with severe AS, or patients with severe AS undergoing CABG or surgery on the aorta or other heart valves.⁶ However, there is less agreement on the optimal AVR timing for asymptomatic patients or those with moderate AS. This relates to the natural history of adult AS whereby there is a prolonged latent period, associated with an inter-individual variable rate of progression to symptomatic status and progression to severe AS. The rate of valvular area decrement ranges between 0.1–0.3 cm2 per year, averaging 0.12 cm2 per year;^6,7 similarly, the systolic pressure gradient across the valve may increase by 5–15 mmHg per year.^6,8 It is currently not possible to predict the progression rate of valvular stenosis in each individual patient, although high outflow velocity (>= 4 m/s), the rate of change in outflow velocity, and presence of atherosclerotic risk factors may provide clues for more rapid progression.^7,9 With this challenge in mind, Kuchulakanti et al. performed a retrospective analysis examining an alternative strategy of percutaneous coronary intervention (PCI) for patients with concomitant CAD and moderate or severe AS.10 They compared the outcomes of PCI among 56 patients with moderate or severe AS who were not candidates for AVR, to 55 patients who had prior AVR. Peri-PCI CKMB elevation was significantly higher among those without prior AVR. Severe AS was the only predictor of death or myocardial infarction (MI) at 1 year. Patients with severe AS who underwent PCI without AVR had a significantly higher death or MI rate at 1 year compared to those who had prior AVR. Those with moderate AS also had worse 6-month and 1-year death or MI rates, although this was not statistically significant. The 1-year mortality was 47.6%, 27.3% and 14.0%, for patients with severe AS without AVR (p = 0.003 vs. those with AVR), moderate AS without AVR (p = 0.31 vs. those with AVR), and those who had AVR, respectively. Importantly, this study reaffirms the practice of combined AVR and CABG for patients with severe AS and concomitant CAD, assuming that they are candidates of such a procedure. It also provides vital information to guide the management of patients with moderate AS and concomitant CAD. Of course, this is a retrospective study that is not entirely powered to evaluate the assessed clinical endpoints. Furthermore, only patients who were not candidates for AVR were included, and thus, the data cannot be extrapolated to lower-risk patients with moderate AS who may be candidates for PCI, in whom outcomes with a percutaneous approach may be expected to be even better. The criteria used for AS severity is also discrepant from the most recent ACC/AHA Task Force guidelines, where severe AS is defined by an area 1.0 to 1.5 cm2. In addition, the authors did not include the mean transvalvular pressure gradient (mean gradient > 50 mmHg for severe AS).¹⁰ Therefore, several of their patients with moderate AS could well have been classified as severe AS with the contemporary criteria. Thus, the actual mortality and MI rate after PCI in a re-classified moderate AS group may be even better than what was reported. Intuitively, an initial less invasive strategy of PCI for significant CAD among patients with moderate AS is an attractive alternative that obviates the immediate need for CABG, and also relinquishes treating physicians from the dilemma of making a premature decision on AVR. Moreover, by avoiding the initial CABG, such an approach would reduce the operative risks of a repeat open-heart surgery if subsequent AVR is required. Studies from the early 1990s have shown that a subsequent AVR among patients who had previously undergone CABG was associated with a higher operative mortality (14–19%).^11,12 To address adequately the utility of PCI among patients with moderate AS, a prospective randomized controlled trial comparing PCI without AVR versus concomitant CABG + AVR would need to be performed. Such an endeavor would require multi-year follow-up, necessitate tremendous resources, is unlikely to be pursued, and would be obsolete by the time it was completed due to continuing technological innovation. Fortunately, in the current era of drug-eluting stents, the lower restenosis rate promises PCI durability and allows the natural progression of mild to moderate AS, until the point when AVR is necessary. Additionally, statins may ultimately be proven to lower the rate of AS progression; observational studies have noted a salutary effect of statins in this regard and randomized evaluations such as the 1,400-patient Simvastatin Ezetimibe Aortic Stenosis (SEAS) trial are ongoing.^13,14 Successful durable revascularization with PCI may also render subsequent AVR safer and better tolerated. Moreover, such an approach may facilitate minimally invasive valve surgery via mini-thoracotomy, with potentially lower operative risks. On the horizon, a combined approach of PCI with percutaneous AVR may soon be feasible,¹⁵ although long-term efficacy will need to be established first (Figure 1). In summary, patients with concomitant severe AS and CAD should presently undergo combined AVR and CABG if they are surgical candidates. The treatment for patients with moderate AS and CAD is in evolution. The approach of initial PCI with subsequent AVR if necessary appears to be a viable strategy, and may be preferable to CABG if complete coronary revascularization can be achieved with PCI.

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