Transcatheter aortic valve replacement (TAVR) has become an established therapy for patients with symptomatic severe aortic stenosis (AS). Many patients referred for TAVR manifest obstructive coronary artery disease (CAD), with a large proportion having undergone prior coronary revascularization. The symptoms of CAD, including chest pain and dyspnea, often overlap with the symptoms of severe AS, which can make the approach to these patients especially challenging. In a large "real-world" experience from the Society of Thoracic Surgeons (STS) and American College of Cardiology (ACC) Transcatheter Valve Therapies Registry, the incidence of CAD among 12,182 patients treated with TAVR was 63%.¹ In the TAVR arm of PARTNER 1 (Placement of Aortic Transcatheter Valve Trial), the rate of prior myocardial infarction (MI) was 19%, and rates of prior percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery were 31 and 37%, respectively.² Despite the high prevalence of CAD in patients treated with TAVR, the rates of early post-TAVR MI are exceedingly low (<1%),^2-4 and the management of concomitant CAD in these patients remains an area of considerable uncertainty.

Invasive coronary angiography is the gold standard to detect CAD and is routinely used to quantify the CAD burden prior to TAVR. Although noninvasive methods to detect CAD such as vasodilator nuclear myocardial perfusion imaging appear to be safe in patients with AS,⁵ coronary angiography is preferred due to insufficient accuracy of nuclear myocardial perfusion imaging (sensitivity and specificity <80%) compared with angiography.⁶ At the time of coronary angiography, fractional flow reserve (FFR) can be performed to assess the functional significance of lesions that are of uncertain significance by angiography alone. The use of intravenous adenosine for FFR measurements appears to be safe despite concerns about the hemodynamic impact of adenosine in AS.⁷ However, there are very limited data about the use of FFR in patients with severe AS, and the accuracy of FFR measurements in these patients has not been well validated. Intravascular ultrasound can also be used at the time of coronary angiography to assess the severity of lesions of uncertain angiographic severity. There are no high-quality data to guide the decision about whether FFR or intravascular ultrasound is the preferred approach to interrogate angiographically moderate lesions, so operator preference and local expertise are important considerations in these cases. Many patients with severe AS referred for TAVR have impaired renal function, which requires that the operator performing coronary angiography limit the dose of contrast medium during the procedure. Biplane imaging is very useful in these patients to allow for judicious use of contrast medium.

Coronary angiography is a key aspect in the preoperative evaluation of patients with severe AS when considering the most appropriate approach to aortic valve replacement. The burden of CAD contributes to the surgical risk, and strategies for revascularization must be carefully weighed when deciding whether TAVR or surgical aortic valve replacement (SAVR) is most appropriate. For example, in younger diabetic patients with severe multivessel CAD or left main trunk CAD, SAVR with concomitant CABG may be the most appropriate approach if the surgical risk is not prohibitive. However, in older frail patients with single vessel or distal CAD and high surgical risk, TAVR with prior or concomitant PCI may be the most appropriate approach. The heart valve team is critical in weighing the data in each case and determining a personalized approach that fits each patient's unique risk profile. For these reasons, use of a heart valve team carries a Class IC recommendation in the most recent iteration of the ACC and American Heart Association valvular heart disease guidelines.⁸

In patients who undergo SAVR with CABG, complete coronary revascularization is the norm, with bypass grafting to all major coronary vessels with obstructive CAD. However, in patients who undergo TAVR with PCI, complete coronary revascularization is rare. We and others advocate a more selective approach targeted at severe proximal coronary lesions that may contribute to symptoms of angina or that subtend a large area of ischemic myocardium and influence risk of periprocedural death or MI.^9,10 Despite recent single-center studies suggesting that incomplete coronary revascularization may be associated with worse outcomes in patients treated with TAVR and PCI,^11,12 the strategy of complete coronary revascularization by PCI prior to TAVR has not been prospectively tested. Complete revascularization typically is not the goal of PCI prior to TAVR; instead, the goal is to minimize the risks of TAVR and to alleviate symptoms. Future studies including the ongoing ACTIVATION (percutaneous coronary intervention prior to transcatheter aortic valve implantation) trial should further elucidate the role of PCI to treat CAD in patients referred for TAVR.

In patients selected for PCI, several technical issues merit careful consideration. Some authors advocate that PCI should be performed prior to TAVR to minimize the risk of rapid ventricular pacing for balloon expandable valves¹³ and other hemodynamic insults in the perioperative period. This approach also offers unobstructed access to the coronary arteries before valve deployment. However, we and other centers have safely performed concomitant TAVR and PCI to minimize the risks associated with performing PCI in patients with severe AS.^14,15 We have previously shown that patients with severe AS can safely undergo PCI; however, those with depressed left ventricular ejection fraction or high STS risk score (>10%) have a 30-day mortality >10% after PCI.¹⁶ There is limited experience with TAVR followed by staged PCI, which is an approach associated with technical challenges including inadequate guide catheter support and limited access to the coronary arteries due to the stent struts of the TAVR valve extending into the aortic sinuses. These issues can be especially challenging in patients treated with self-expanding valves, including the CoreValve (Medtronic CV Luxembourg S.a.r.l., Luxembourg) and Evolut R (Medtronic, Inc., Minneapolis, MN) systems. At our institution, our routine approach is to perform PCI as a staged procedure prior to TAVR except in selected few cases in which aorto-ostial lesions have to be treated or there is a technically simple lesion to treat with normal renal function.

Despite the fact that the TAVR population includes many frail and/or elderly patients with multiple bleeding risk factors, in our practice many patients can be safely treated with drug-eluting stents rather than bare-metal stents using contemporary second-generation drug-eluting stent platforms in which DAPT can be stopped with reasonably low rates of stent thrombosis after only 3 months if needed.^17,18 In our opinion, there is typically no role for bare-metal stents in this setting. With the decreasing proportion of patients who require non-transfemoral access for TAVR in contemporary practice, it is uncommon to encounter patients who require both coronary revascularization and surgical access for TAVR. In any case, TAVR can be performed with DAPT with alternative access. We treat CAD in these patients similarly to how we treat transfemoral patients.

In summary, many patients referred for TAVR manifest concomitant CAD. Whether to revascularize CAD in TAVR candidates remains an area of uncertainty and ongoing clinical investigation. In the absence of robust data on this topic, we advocate a selective approach of performing PCI in lesions that subtend large areas of ischemic myocardium, proximal lesions in major epicardial vessels, and/or lesions that contribute to angina. As a general approach, we suggest the analogy of performing PCI for lesions that might be revascularized prior to major non-cardiac surgery. Ongoing studies in this arena should provide additional insight into the management of these patients in the coming years.

References

1. Holmes DR Jr, Brennan JM, Rumsfeld JS, et al. Clinical outcomes at 1 year following transcatheter aortic valve replacement. JAMA 2015;313:1019-28.
2. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363:1597-607.
3. Mohr FW, Holzhey D, Möllmann H, et al. The German Aortic Valve Registry: 1-year results from 13,680 patients with aortic valve disease. Eur J Cardiothorac Surg 2014;46:808-16.
4. Smith CR, Leon MB, Mack MJ, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364:2187-98.
5. Samuels B, Kiat H, Friedman JD, Berman DS. Adenosine pharmacologic stress myocardial perfusion tomographic imaging in patients with significant aortic stenosis. Diagnostic efficacy and comparison of clinical, hemodynamic and electrocardiographic variables with 100 age-matched control subjects. J Am Coll Cardiol 1995;25:99-106.
6. Hussain N, Chaudhry W, Ahlberg AW, et al. An assessment of the safety, hemodynamic response, and diagnostic accuracy of commonly used vasodilator stressors in patients with severe aortic stenosis. J Nucl Cardiol 2016 Mar 15 [Epub ahead of print].
7. Stanojevic D, Gunasekaran P, Tadros P, et al. Intravenous Adenosine Infusion is Safe and Well Tolerated During Coronary Fractional Flow Reserve Assessment in Elderly Patients With Severe Aortic Stenosis. J Invasive Cardiol 2016;28:357-61.
8. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014;63:2438-88.
9. Goel SS, Ige M, Tuzcu EM, et al. Severe aortic stenosis and coronary artery disease--implications for management in the transcatheter aortic valve replacement era: a comprehensive review. J Am Coll Cardiol 2013;62:1-10.
10. Gasparetto V, Fraccaro C, Tarantini G, et al. Safety and effectiveness of a selective strategy for coronary artery revascularization before transcatheter aortic valve implantation. Catheter Cardiovasc Interv 2013;81:376-83.
11. Gautier M, Pepin M, Himbert D, et al. Impact of coronary artery disease on indications for transcatheter aortic valve implantation and on procedural outcomes. EuroIntervention 2011;7:549-55.
12. Witberg G, Lavi I, Harari E, et al. Effect of coronary artery disease severity and revascularization completeness on 2-year clinical outcomes in patients undergoing transcatether aortic valve replacement. Coron Artery Dis 2015;26:573-82.
13. Selle A, Figulla HR, Ferrari M, et al. Impact of rapid ventricular pacing during TAVI on microvascular tissue perfusion. Clin Res Cardiol 2014;103:902-11.
14. Salhab KF, Al Kindi AH, Lane JH, et al. Concomitant percutaneous coronary intervention and transcatheter aortic valve replacement: safe and feasible replacement alternative approaches in high-risk patients with severe aortic stenosis and coronary artery disease. J Card Surg 2013;28:481-3.
15. Penkalla A, Pasic M, Drews T, et al. Transcatheter aortic valve implantation combined with elective coronary artery stenting: a simultaneous approach†. Eur J Cardiothorac Surg 2015;47:1083-9.
16. Goel SS, Agarwal S, Tuzcu EM, et al. Percutaneous coronary intervention in patients with severe aortic stenosis: implications for transcatheter aortic valve replacement. Circulation 2012;125:1005-13.
17. Kedhi E, Stone GW, Kereiakes DJ, et al. Stent thrombosis: insights on outcomes, predictors and impact of dual antiplatelet therapy interruption from the SPIRIT II, SPIRIT III, SPIRIT IV and COMPARE trials. EuroIntervention 2012;8:599-606.
18. Palmerini T, Biondi-Zoccai G, Della Riva D, et al. Stent thrombosis with drug-eluting stents: is the paradigm shifting? J Am Coll Cardiol 2013;62:1915-21.

Keywords: Adenosine, Aged, Angina Pectoris, Aortic Valve, Aortic Valve Stenosis, Coronary Angiography, Coronary Artery Bypass, Coronary Artery Disease, Diabetes Mellitus, Drug-Eluting Stents, Heart Valve Diseases, Myocardial Infarction, Myocardial Perfusion Imaging, Myocardium, Percutaneous Coronary Intervention, Perioperative Period, Risk Factors, Stroke Volume, Surgeons, Thrombosis, Transcatheter Aortic Valve Replacement, Vasodilator Agents, Heart Valve Diseases

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