Author + information
- Received July 21, 2016
- Revision received August 19, 2016
- Accepted September 14, 2016
- Published online December 12, 2016.
- Stephen Ramee, MDa,
- Saif Anwaruddin, MDb,
- Gautam Kumar, MDc,
- Robert N. Piana, MDd,
- Vasilis Babaliaros, MDe,
- Tanveer Rab, MDe,
- Lloyd W. Klein, MDf,∗ (, )
- Aortic Stenosis AUC Writing Group,
- Interventional Section of the Leadership Council of the American College of Cardiology
- aOchsner Medical Center, New Orleans, Louisiana
- bHospital of the University of Pennsylvania, Philadelphia, Pennsylvania
- cEmory University/Atlanta VA Medical Center, Atlanta, Georgia
- dVanderbilt University Medical Center, Nashville, Tennessee
- eEmory University School of Medicine, Atlanta, Georgia
- fRush Medical College, Chicago, Illinois
- ↵∗Reprint requests and correspondence:
Dr. Lloyd W. Klein, Rush Medical College, 3000 North Halsted, Suite #625, Chicago, Illinois 60614.
Transcatheter aortic valve replacement (TAVR) is an effective, nonsurgical treatment option for patients with severe aortic stenosis. The optimal treatment strategy for treating concomitant coronary artery disease (CAD) has not been tested prospectively in a randomized clinical trial. Nevertheless, it is standard practice in the United States to perform coronary angiography and percutaneous coronary intervention for significant CAD at least 1 month before TAVR. All existing clinical trials were designed using this strategy. Therefore, it is wrong to extrapolate current American College of Cardiology/American Heart Association Appropriate Use Criteria against invasive procedures in asymptomatic patients to the TAVR population when evaluating the quality of care by cardiologists or hospitals. In this statement from the Interventional Section Leadership Council of the ACC, it is recommended that percutaneous coronary intervention should be considered in all patients with significant proximal coronary stenosis in major coronary arteries before TAVR, even though the indication is not covered in current guidelines.
Transcatheter aortic valve replacement (TAVR) is an effective, nonsurgical treatment option for patients with severe aortic stenosis (AS) that will increasingly be performed in the future. The optimal treatment strategy for treating concomitant coronary artery disease (CAD) has not been tested prospectively in a randomized clinical trial. Nevertheless, it is standard practice in the United States to perform coronary angiography and percutaneous coronary intervention (PCI) for significant CAD ≥1 month before TAVR.
In the United States, TAVR was approved for clinical use by the Food and Drug Administration (FDA) on November 2, 2011, and by the Centers for Medicare and Medicaid Services (CMS) on May 1, 2012 (1,2). The 2011 American College of Cardiology Foundation/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACCF/AHA/SCAI) guideline for PCI (3), the ACCF/SCAI/Society of Thoracic Surgery (STS)/American Association for Thoracic Surgery (AATS)/AHA/American Society of Nuclear Cardiology (ASNC) 2009 appropriateness criteria for coronary revascularization (4), and the ACCF/SCAI/STS/AATS/AHA/ASNC/Heart Failure Society of America/Society of Cardiovascular Computed Tomography 2012 appropriate use criteria for coronary revascularization focused update (5) were completed before the role of PCI in pre-TAVR patients became a clinical issue. The 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery does not directly apply to TAVR, but gives Class III (no benefit) recommendations for routine diagnostic angiography and for routine PCI in asymptomatic patients before non-cardiac surgery (6). There is no evidence proving that TAVR without prior PCI of severe coronary lesions is safe, because all prior randomized clinical trials that led to approval of TAVR required revascularization of significant coronary stenoses in main branch epicardial vessels within 30 days of TAVR (7–10). Therefore, it would be wrong to extrapolate current ACC/AHA recommendations against invasive procedures in asymptomatic patients to the TAVR population when evaluating the quality of care by cardiologists or hospitals.
The discordance between current professional society recommendations, which have been silent on this issue, and current practice highlights the need to update this topic in the ACC documents portfolio. This consensus statement from the Interventional Section Leadership Council of the American College of Cardiology is intended to address the role of coronary angiography and PCI in candidates for TAVR.
TAVR was approved by the FDA and funded by CMS based on the PARTNER I (Placement of Aortic Transcatheter Valves) and the US CoreValve High Risk Study randomized trials (7,8). PARTNER IA compared TAVR versus surgical aortic valve replacement (SAVR) in patients with a predicted operative mortality of 15% and/or a minimum STS score of 10 (7). The protocol required all major coronary arteries with significant stenoses to undergo PCI before TAVR if they were randomized to TAVR. The outcomes in both groups were comparable. The FDA labeling and the ACCF/AATS/SCAI/STS expert consensus document reproduce the trial protocol (9). CMS and all other third-party payers in the United States follow the recommendations by implication for PCI in all potential TAVR patients ≥30 days before TAVR (10). In fact, patients with “untreated clinically significant coronary artery disease requiring revascularization” were excluded from the PARTNER and CoreValve trials (7,8). TAVR has not been studied in patients with significant CAD without prior PCI.
Before TAVR, this was not a relevant issue. During SAVR, coronary artery bypass grafting (CABG) and aortic valve replacement are performed simultaneously. In 1,308 consecutive patients with significant CAD (≥50% stenosis) undergoing SAVR with or without CABG between 2001 and 2010, the 5- and 8-year mortality rates were lower in patients undergoing revascularization at the time of SAVR (11,12).
There are several potential limitations to physiologic assessment of CAD in the setting of PCI before TAVR. Exercise testing in patients with AS has poor diagnostic accuracy for the evaluation of concurrent CAD and is contraindicated in patients with symptomatic severe AS (13). Fractional flow reserve measurement may have a role, but there are limited data in patients with AS (14). Increased afterload and left ventricular hypertrophy could theoretically render the measurement of fractional flow reserve misleading and adenosine administration contraindicated. Instantaneous flow reserve may obviate some of these concerns, but given the diminished flow reserve in AS due to higher resting flow, there may be inherent inaccuracy (15). In the setting of AS, exertional dyspnea or chest pain may be due to the combination of aortic valve disease and CAD. PCI alone may resolve symptoms. Therefore, the decision to pursue PCI and TAVR must be made considering all clinical information.
Reported Outcomes with PCI in Patients with AS
Severe AS has previously been considered a contraindication to PCI. The risk of PCI in this setting was considered to be high, because of physiologic considerations and concern for complications (3). However, recent studies have evaluated PCI outcomes in AS and have shown that the results can be favorable if patients are carefully selected (16–20).
Goel et al. (16) demonstrated that, when PCI is performed in patients with AS, an association of increased short-term mortality or procedural complications compared with propensity-matched patients without AS was not established. The study group included 254 patients. The indications were acute coronary syndromes, congestive heart failure, or severe stable angina, and CAD, rather than the AS, was thought to be causing symptoms. Patients with left ventricular ejection fraction (LVEF) of <30% and an STS score of >10 were at greatest risk for 30-day mortality after PCI.
Gasparetto et al. (17) reported a single-center prospective registry (PUREVALVE Registry) that included 191 consecutive patients with severe AS referred for TAVR. PCI was performed only for stenoses involving proximal or mid segments of major coronary arteries. PCI was performed after considering symptoms, the extent of myocardium at risk, proven ischemia by invasive or non-invasive testing, and the technical feasibility of PCI. Chronic total occlusions and lesions in small vessels (reference diameters <2.5 mm) were not considered for PCI. Of the 191 patients who underwent TAVR, CAD was present in 113 (59.2%) and PCI was performed before TAVR in 39 (20.4%). Although this was a small observational study, the overall 30-day mortality did not differ significantly between patients with CAD post-PCI versus no CAD (5.7% vs. 2.9%; p = NS). These results suggest that a selective, clinically driven PCI strategy before TAVR may be a reasonable strategy.
Abdel-Wahab et al. (18) reported retrospectively on 55 patients who underwent PCI before TAVR with the CoreValve (Medtronic, Minneapolis, Minnesota) compared with 70 patients who underwent TAVR alone. No difference was observed between the groups with respect to 30-day mortality, myocardial infarction, major bleeding, major vascular complications, combined safety endpoint, or adverse events at 6 months.
Wendt et al., in another single-center study (19), compared the outcomes of 184 patients undergoing SAVR plus CABG with 59 patients undergoing TAVR plus PCI within 12 months. Although the TAVR group was higher risk, TAVR plus PCI produced similar results for in-hospital mortality as SAVR plus CABG. Only LVEF was predictive of outcome.
Outcomes in higher risk patients undergoing left main (LM) PCI have also been demonstrated to be reasonable before TAVR. In a multicenter series in 128 matched pairs requiring LM PCI before TAVR versus those not requiring LM PCI, there was no difference in 1-year mortality (20). However, performing LM PCI for a TAVR-related complication was associated with greater 30-day and 1-year mortality.
An editorial (21) posed the challenge as to whether TAVR could be performed safely despite severe CAD and whether, left untreated, there would be an impact on symptoms and long-term survival. Because TAVR was approved only for patients at extreme risk for surgery at the time of this editorial, it was concluded that “the threshold for PCI should be high unless it will affect the safety of the procedure” (21). However, it was acknowledged that as TAVR expanded to lower risk patients, the optimal strategy would then need to be reassessed. Since that time, there has been substantial experience selecting patients and performing PCI.
Specific Clinical and Anatomic Considerations in Patient Selection
When the patient is symptomatic with combined CAD and AS, and TAVR is being considered as a treatment option, the risks of PCI must be evaluated from a different perspective than for most patients with stable ischemic heart disease. Untreated significant stenoses may potentially exclude patients from consideration for TAVR. Conversely, if the PCI procedure poses a high risk, then the advisability of a TAVR strategy may need to be reevaluated. These issues are unique and differ significantly from the usual PCI considerations: symptomatology, activity levels, and noninvasive testing are less appropriate to the decision-making process. All TAVR candidates may be symptomatic with either angina or heart failure, but it is difficult to determine whether the CAD or the AS, or a combination, are the cause. Medication use also deviates from standard practice, because anti-anginal agents may be contraindicated due to their negative hemodynamic effects.
PCI can be performed safely before TAVR in carefully selected cases with truly severe or life-threatening disease (16–20). The decision to perform PCI should take into consideration LVEF, lesion location and severity, morphologic complexity, and technical feasibility. When the LVEF is <30%, or the STS score >10, patients are at the highest risk of 30-day mortality after PCI (10). These are important factors to consider in the risk–benefit ratio, and special deliberation is warranted. The selection of drug-eluting versus bare metal stents may also be weighed in this population who are elderly and have increased risk for gastrointestinal and other bleeding, which may be increased by longer duration dual antiplatelet therapy. Recent-guidelines give a class IIb recommendation of 3 months of dual antiplatelet therapy for drug eluting stents for those at high risk of bleeding, which may be applicable in this setting (22).
Generally, only stenoses of >70% in the proximal epicardial arteries should be considered for PCI (16–20). Stenoses in the right coronary artery before the posterior descending artery may be physiologically proximal and hence appropriate targets. Branch arteries usually should not be treated, although a large branch may be considered. LM and right coronary artery ostial stenoses require special consideration because the transcatheter heart valve can crush the overhanging stent frame. In this scenario, concomitant procedures may decrease the patient risk. Severely calcified stenoses pose distinct technical problems. Atherectomy is a complex and high-risk procedure in these patients, and the risk–benefit ratio must be weighed carefully.
Given that these patients are TAVR candidates primarily because they are not optimal surgical candidates, patient frailty, bleeding, and vascular access must be fully considered. In very high-risk cases, CABG after TAVR is usually not feasible but an off pump left internal mammary artery to left anterior descending procedure may be considered. Stenting after TAVR can sometimes be challenging, particularly with regard to adequate guide position, given the position of the aortic prosthesis, particularly with certain valve designs, which may limit subsequent access to the coronary ostia.
The management of CAD in patients undergoing TAVR should be individualized based on the patient’s overall clinical condition and anatomy. These patients have contraindications to stress testing. Based on previous clinical trial protocols and the CMS mandate (7–11), all patients with AS undergoing evaluation for TAVR require coronary angiography. PCI should be considered for major coronary arteries with significant proximal stenosis before TAVR, even though the indication is not covered in current guidelines (3–5).
We propose the use of a clinical algorithm to assess the need for PCI before TAVR (Figure 1). In patients with >70% stenosis in a proximal epicardial vessel or the LM, the decision to perform PCI should be made before or at the time of TAVR as long as the risk of the procedure does not outweigh the potential benefits. In the setting where the coronary stenoses are located in branch or mid/distal epicardial vessels, with small areas of ischemia, the decision whether to perform PCI may be postponed until after TAVR, unless access to the coronary artery will be limited by the transcatheter valve. In addition to assessment of procedural risk, consideration should be given to whether CAD may be contributing to the patient’s symptoms. In those situations where it may be the primary cause of symptoms, PCI may be performed, and the need for TAVR reevaluated. We do not advocate performing PCI on a chronic total occlusion in the absence of ischemia or symptoms before TAVR. As TAVR becomes more widely practiced in patients with a better long-term prognosis, these considerations will be of greater importance.
Dr. Anwaruddin serves as a consultant/speaker for Edwards and Medtronic. Dr. Babaliaros serves as a consultant for Edwards Lifesciences and Abbott Vascular. Dr. Piana serves as a Quality Reviewer for Cardiovascular Peer Review and on the Data Safety Monitoring Boards for the Harvard Clinical Research Institute, Axio Research, and W.L. Gore. Dr. Ramee has received honoraria of <$10,000 from Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- American Association for Thoracic Surgery
- American College of Cardiology Foundation
- American Heart Association
- aortic stenosis
- American Society of Nuclear Cardiology
- coronary artery bypass grafting
- coronary artery disease
- Centers for Medicare and Medicaid Services
- Food and Drug Administration
- left main
- left ventricular ejection fraction
- percutaneous coronary intervention
- surgical aortic valve replacement
- Society for Cardiovascular Angiography and Interventions
- Society of Thoracic Surgery
- transcatheter aortic valve replacement
- Received July 21, 2016.
- Revision received August 19, 2016.
- Accepted September 14, 2016.
- 2016 American College of Cardiology Foundation
- ↵Edwards SAPIEN Transcatheter Heart Valve (THV) - P100041. Available at: http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/DeviceApprovalsandClearances/Recently-ApprovedDevices/ucm280840.htm. Accessed November 14, 2016.
- ↵Decision Memo for Transcatheter Aortic Valve Replacement (TAVR) (CAG- 00430N). Available at: https://www.cms.gov/medicare-coverage-database/details/nca-decision-memo.aspx?NCAId=257. Accessed November 14, 2016.
- Levine G.N.,
- Bates E.R.,
- Blankenship J.C.,
- et al.
- Patel M.R.,
- Dehmer G.J.,
- Hirshfeld J.W.,
- Smith P.K.,
- Spertus J.A.
- Patel M.R.,
- Dehmer G.J.,
- Hirshfeld J.W.,
- Smith P.K.,
- Spertus J.A.
- Fleisher L.A.,
- Fleischmann K.E.,
- Auerbach A.D.,
- et al.
- Holmes D.R. Jr..,
- Mack M.J.,
- Kaul S.,
- et al.
- ↵Centers for Medicare and Medicaid Services (CSM). Available at: http://www.accessdata.fda.gov/cdrh_docs/pdf10/p100041a.pdf. Accessed March 20, 2016.
- Nishimura R.A.,
- Otto C.M.,
- Bonow R.O.,
- et al.
- Danson E.,
- Hansen P.,
- Sen S.,
- Davies J.,
- Meredith I.,
- Bhindi R.
- Di Gioia G.,
- Pellicano M.,
- Toth G.G.,
- et al.
- Paradis J.M.,
- Fried J.,
- Nazif T.,
- et al.
- Goel S.S.,
- Agarwal S.,
- Tuzcu E.M.,
- et al.
- Chakravarty T.,
- Sharma R.,
- Abramovitz Y.,
- et al.
- Kodali S.K.,
- Moses J.W.
- Levine G.,
- Bates E.,
- Bittl J.,
- et al.