Aortic stenosis and coronary artery dise

REVIEW European Heart Journal (2014) 35, 2069–2082 doi:10.1093/eurheartj/ehu247 Clinical update Aortic stenosis and coronary artery disease: What we know? What don’t we know? A comprehensive review of the literature with proposed treatment algorithms Columbia University Medical Center, New York, NY, USA; 2Cardiovascular Research Foundation, New York, NY, USA; and 3Quebec Heart and Lung Institute, Quebec, Canada Received November 2013; revised May 2014; accepted 26 May 2014; online publish-ahead-of-print 26 June 2014 Aortic valve stenosis is the most common form of valvular heart disease in the elderly population and occurs frequently in conjunction with coronary artery disease The standard treatment option for patients with these two conditions has been surgical aortic valve replacement and coronary artery bypass grafting The arrival of transcatheter aortic valve replacement has considerably shifted the treatment paradigms Nevertheless, a lot of questions remain unanswered regarding the management of coronary artery disease in the setting of the transcatheter options for severe aortic stenosis This article includes a comprehensive review of the literature and seeks to describe the actual knowledge on the topic of aortic stenosis and concomitant coronary artery disease Keywords Coronary artery disease † Aortic stenosis † Percutaneous coronary intervention † Transcatheter aortic valve replacement † Surgical aortic valve replacement Introduction Aortic valve stenosis is the most common form of valvular heart disease in the elderly population and frequently occurs in conjunction with coronary artery disease (CAD).1,2 Compelling epidemiological and histopathological data suggest that degenerative calcific aortic stenosis (AS) is an active and multifaceted disease process that resembles both atherosclerosis and elastocalcinosis.3 Furthermore, risk factors for AS have been shown to be similar to those for atherosclerosis and CAD.4 It is therefore not surprising that significant CAD is often present in patients with severe AS The prevalence of CAD also increases with age, such that it is present in more than 50% of patients with AS over 70 years of age and 65% of patients with AS over 80 years of age.5 The standard treatment option for patients with AS and CAD has been surgical aortic valve replacement (SAVR) and concomitant coronary artery bypass grafting (CABG) However, over the last 10 years, treatment paradigms have shifted due to the availability of transcatheter aortic valve replacement (TAVR) for high-risk patients However, in the setting of this less-invasive approach, the appropriate management of coexistent significant CAD still remains unclear This article, which includes a comprehensive review of the literature, seeks not only to describe the actual knowledge on the topic of AS and concomitant CAD, but also to identify the unanswered questions, especially those emerging in the era of TAVR Aortic valve calcification and prevalence of coronary artery disease The prevalence of CAD in patients undergoing surgical aortic valve replacement has been shown to increase with both age and the presence of valve calcification.1,2,6 This was demonstrated in a large * Corresponding author: 2725 Chemin Sainte-Foy, Quebec, Quebec, Canada G1V 4G5 Tel: +1 418 656 4598, Fax: +1 418 656 4581, Email: jm.paradis@criucpq.ulaval.ca Published on behalf of the European Society of Cardiology All rights reserved & The Author 2014 For permissions please email: journals.permissions@oup.com Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 Jean-Michel Paradis 1,2,3*, Justin Fried 1, Tamim Nazif 1, Ajay Kirtane 1,2, Kishore Harjai 1, Omar Khalique 1, Kendra Grubb 1, Isaac George 1, Rebecca Hahn 1, Mathew Williams1, Martin B Leon 1,2, and Susheel Kodali 2070 Coronary flow in aortic stenosis The coronary flow reserve (CFR) is defined as the maximal increase in myocardial blood flow above its resting level for a given perfusion pressure when coronary vasculature is maximally dilated It therefore represents an integrated measure of flow through both the large epicardial coronary arteries and the microcirculation Narrowing of the epicardial coronaries or dysfunction of the coronary circulation may lead to an abnormal CFR even in the absence of angiographically proven atherosclerotic disease Patients with AS and angiographically normal coronary arteries have been shown to have decreased CFR, which limits the capacity of the coronary circulation to increase flow to match myocardial oxygen demand This impairment of CFR is certainly one of the key elements responsible for myocardial ischaemia in AS patients and may contribute to the development of symptoms, LV dysfunction, and adverse outcomes.10 The mechanisms underlying the reduction of CFR in patients with AS remains unclear Concentric LV hypertrophy was previously believed to be the major cause of the reduction in CFR in patients with AS, but recent data suggest that the abnormally high LV workload induced by AS may be the key factor In fact, reduced CFR correlates better with haemodynamic indexes of AS severity (valve effective orifice area and transvalvular pressure gradient) than with LV mass.11 Additionally, it has been demonstrated that coronary microcirculation is impaired in ventricles suffering from long-term pressure load It stands to reason that these functional alterations of intramyocardial coronary arterioles may be the cause of the reduction in CFR in patients with severe AS.12 Fractional flow reserve (FFR) has been shown to be a valuable tool for physiology-guided lesion assessment, and routine FFR in addition to coronary angiography has improved the outcome of percutaneous coronary intervention (PCI).13 In patients with AS, evaluation of induced myocardial ischaemia is controversial 14 and in fact, exercise testing is contraindicated in severe AS Nevertheless, a recent case series showed the safety and benefits of FFR assessment in patients with severe AS and concomitant CAD.15 Likewise, in another study, dipyridamole myocardial perfusion tomography has been demonstrated to be of high diagnostic value (sensitivity 100%, specificity 91%) and safe in the detection of CAD in patients with severe AS.16 Figure Percentages of simultaneous coronary artery bypass grafting surgery and surgical aortic valve replacement according to the Swedish registry.7 CABG, coronary artery bypass graft surgery; SAVR, surgical aortic valve replacement Symptoms and coronary artery disease in patients with aortic stenosis The presence of symptoms is of limited utility in detecting CAD in patients with AS because angina pectoris is the most common presenting symptom in both disease states Various series have demonstrated that the prevalence of CAD in patients with AS is similar in those with (43%) and without (29%) angina In one study, the sensitivity, specificity, positive predictive value, and negative predictive value of angina in identifying coronary disease was 68, 46, 43, and 71%, respectively.1 Studies have consistently reported that about half of patients with AS and angina pectoris have angiographically significant CAD.17 In patients with AS and angina but without CAD, it has been postulated that diminished CFR leads to an imbalance between myocardial oxygen supply and demand resulting in angina Given the poor discriminatory capacity of angina for predicting CAD in patients with AS, coronary angiography is recommended in the following: symptomatic patients before AVR in men older than 35 years; pre-menopausal women older than 35 years with coronary risk factors, as well as asymptomatic men older than 45 years; women older than 55 years; and those with two or more coronary risk factors18 (Table 1) Impact of coronary artery disease on the outcomes of surgical aortic valve replacement The presence of CAD has been demonstrated to increase the procedural risk of surgical aortic valve replacement,19,20 and coronary revascularization is generally recommended at the time of surgery Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 Swedish registry where CABG occurred simultaneously with SAVR in 7.2% of patients aged ≤50 years, 30.2% of patients aged between 51 and 60 years, 41.2% of patients aged 61– 70 years, and 51.2% of patients aged ≥71 years (Figure 1).7 In a study of 388 patients (mean age 72 years) with aortic valve calcification who underwent coronary angiography, there was a significant association between aortic valve calcification and significant CAD Thus, aortic valve calcification can serve as a marker for atherosclerosis of the coronary arteries.6 The presence of aortic valve calcification, like mitral annular calcification (MAC), almost certainly arises from the same systemic vascular atherosclerotic process that leads to CAD In a postmortem study of persons aged 65 years, Roberts et al.3,8 showed that 100% of people with aortic valve calcification or MAC had calcific deposits in one or more coronary arteries This finding is further supported by pathological studies4,9 showing that collections of foam cells, which represent early atherosclerotic lesions, may be observed on the endothelium of both the epicardial coronary arteries and the aortic valve cusps as early as the second and third decades of life J.M Paradis et al Aortic stenosis and coronary artery disease Table Indications to proceed with a coronary angiogram prior to surgical aortic valve replacement Symptomatic men older than 35 years Asymptomatic men older than 45 years Pre-menopausal women older than 35 years with coronary risk factors Women older than 55 years or post-menopausal Patients with two or more coronary risk factors Patients with a history of coronary artery disease Patients undergoing a cardiac catheterization to clarify the severity of the valve disease Outcomes of percutaneous coronary intervention in patients with severe aortic stenosis Because surgical AVR and CABG has been considered the preferred treatment option for patients with concomitant AS and CAD, PCI has been performed infrequently in this population The outcomes data for PCI in patients with severe AS and CAD is therefore limited to observational studies In the largest study to date comparing patients with and without severe AS who underwent PCI, Goel et al 25 analysed the short-term outcomes of 254 patients with severe AS and CAD who were treated with PCI over a 10-year period PCI was performed in these patients for one or more of the following reasons: (i) clinical presentation with an acute coronary syndrome (unstable angina, NSTEMI, STEMI) and a severe coronary lesion (≥70%) that was thought to be responsible for the presentation; (ii) stable angina, the symptoms of which were thought to be attributable to CAD rather than AS by the treating cardiologist or if the patient was deemed high risk for CABG and SAVR; (iii) NYHA class III to IV congestive heart failure with unclear contribution of CAD and AS to the symptomatology and the patient was deemed to be high risk for SAVR by the managing team consisting of a cardiologist and a cardiac surgeon These patients were compared with a propensity-matched cohort of patients without AS who underwent PCI in the same period at the same institution The study found no differences between those with and without AS with respect to 30-day mortality (4.3 vs 4.7%, HR 0.51–1.69, P ¼ 0.2) The high short-term mortality rate observed in both groups is a testament to the high-risk nature of this patient population Subgroup analysis of the patients with severe AS showed that patients with a low EF (≤30%) or a high STS score (≥10) had a significantly higher 30-day post-PCI mortality Other short-term complications of PCI, including procedural death, haemodynamic compromise during PCI, peri-procedural MI, coronary dissection, coronary perforation, cardiac tamponade, access site haematoma, retroperitoneal bleed, and contrast nephropathy, did not differ significantly between groups From these data, the authors concluded that PCI could be performed in patients with severe AS without increased risk of shortterm mortality or procedural complications compared with similar patients without concomitant AS With respect to long-term outcomes, at a mean follow-up of 3.7 years, 29% of patients with severe AS had undergone SAVR with a mean duration of 15.5 months between PCI and SAVR, and CABG was performed with SAVR in 71% of these patients Long-term mortality was 42.5% in AS patients who underwent SAVR compared with 68% in AS individuals who did not undergo SAVR and 46.7% in the control group without AS In the multivariable analysis incorporating SAVR as a time-dependent covariate, independent predictors of long-term mortality for patients with severe AS undergoing PCI were age, ejection fraction ,30%, chronic kidney disease, diabetes mellitus, and chronic obstructive pulmonary disease The study has several limitations worth mentioning Most importantly, it was an observational, single-centre study and consequently prone to bias Also, only about 22% of patients in each group underwent PCI with drug eluting stents (DES), making this largely a bare metal stent (BMS) study Outcomes of hybrid procedures with surgical aortic valve replacement and percutaneous coronary intervention As noted earlier, the traditional treatment for severe AS with concomitant CAD has been combined AVR and CABG This combined Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 The American College of Cardiology and American Heart Association guidelines on valvular heart disease advocate, as a Class recommendation, that patients undergoing AVR with significant stenoses (greater than or equal to 70% reduction in luminal diameter) in major coronary arteries should be treated with bypass grafting.18 The European Society of Cardiology guidelines also recommend complete revascularization in patients with severe AS undergoing SAVR to improve long-term outcomes.21 However, interventions combining AVR and coronary artery bypass grafting are associated with higher post-operative mortality than AVR alone.22 Data from 10 000 patients undergoing heart surgery from the New York Cardiac Surgery Reporting System showed that mortality for isolated valve surgery was 4.4% compared with 8.9% for valve surgery and CABG.23 This is supported by a recent, large observational study comparing outcomes of patients with isolated AS who underwent AVR with patients with severe AS and CAD who underwent AVR and CABG.24 All patients in the study underwent coronary angiography as part of the pre-operative evaluation for AVR, and CAD was defined as at least one major epicardial artery (left main trunk, left-anterior descending coronary artery, left circumflex coronary artery, and right coronary artery) with at least 50% stenosis or a history of PCI The results confirmed earlier findings that both short- and long-term mortality was increased with concomitant AVR and CABG However, once the patients were propensitymatched to account for differences in baseline comorbidities, survival was similar between patients with isolated AS and both AS and CAD through 10 years of follow-up (93 vs 93%, 80 vs 80%, and 55 vs 50% at 1,5, and 10 years, respectively) This suggests that the higher risk profile of patients undergoing both AVR and CABG may be responsible for their increased operative and long-term risk 2071 2072 limited to 30 days The MI-AVR group and control group also differed in regards to the time period when the procedures were performed with the patients who underwent PCI selected from 2009 to 2011 compared with the conventional AVR/CABG patients who were treated from 2005 to 2011 Overall, the available studies demonstrate the feasibility of a hybrid approach to the treatment of AS and CAD with staged or single setting PCI and AVR An important issue is the timing of the procedures and management of anti-platelet therapies Future studies, including randomized trials are necessary to clarify the clinical utility of this treatment strategy, particularly with respect to long-term outcomes While awaiting further confirmatory data, Figure summarizes the treatment algorithm used at Columbia University Medical Center Transcatheter aortic valve replacement According to a recent EuroHeart survey, as many as one-third of all potential surgical AVR candidates not undergo surgery.29 This may be due in part to prohibitive surgical risk in these patients The estimated operative risk may be higher due to advanced age, comorbid medical conditions, or the need for combined valve and coronary surgery Over the past several years, TAVR has emerged as an attractive therapeutic option in patients with severe symptomatic AS who are inoperable or high-risk candidates for surgical AVR Multiple studies and registries have demonstrated that the prevalence of CAD in patients undergoing TAVR ranges from 47.6 to 74.9%.3,6,8,30 – 45 Coronary angiography is therefore strongly recommended in the assessment of eligibility for TAVR, although the optimal management of CAD in the context of TAVR has not yet been established.3,4,8,9,46 Myocardial infarction after transcatheter aortic valve replacement Excluding the initial feasibility study of transapical TAVR, which showed a rate of MI of 15%,45 studies have shown the rate of periprocedural MI after TAVR to be between and 4.6%.10,11,30 – 44 However, the available studies have used non-uniform definitions of MI with different thresholds of cardiac biomarker elevation One study by Rodes-Cabau et al.47 demonstrated that a greater degree of myocardial injury was associated with less improvement in LVEF and higher cardiac mortality at follow-up Further research is required to definitively establish the clinical impact of periprocedural MI after TAVR Impact of coronary artery disease on the outcomes of transcatheter aortic valve replacement The few published studies evaluating the impact of concomitant CAD on procedural outcomes and long-term survival after TAVR have yielded conflicting results (Table 3).13,17,20,48 – 51 Dewey et al.20 Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 procedure carries a mortality rate nearly double that of isolated AVR (4.4 vs ≏9%).3,23 Combined AVR/CABG is also less favourable in patients with poor or limited conduit vessels, patients presenting with ACS, and patients requiring valve reoperation For these reasons, it has been proposed that some patients may benefit from a hybrid procedure in which PCI is combined with SAVR (Table 2) Thus, this strategy divides the high-risk surgery into two potentially lower-risk procedures Nevertheless, an important challenge of this hybrid approach has been the appropriate timing of PCI given the necessity of dual anti-platelet therapy use and its potential to increase the bleeding risk in SAVR It is worthwhile to note that studies examining hybrid procedures have included both minimally invasive AVR (MI-AVR) as well as traditional AVR via median sternotomy with a trend towards more MI-AVR Combining PCI with surgical valve replacement as treatment for concomitant CAD was first investigated by Byrne et al.26 in a singlecentre retrospective study of 26 patients who underwent PCI either for ACS (24 patients) or for a complex re-operative valve surgery (two patients) followed by aortic or mitral valve surgery using either a minimally invasive or traditional approach With valve replacement (58% primary, 42% re-operative) occurring a median of days after PCI, operative mortality was 3.8%, which was significantly lower than the STS-predicted mortality of 22% Of note there was an extremely high rate of blood transfusion (85%), likely due to the requirement for dual anti-platelet therapy following PCI Survival at 1, 3, and years was 78, 56, and 44%, respectively While this study was limited by its small sample size and heterogeneous patient population, it demonstrated the feasibility of performing PCI prior to AVR The idea of combining AVR with PCI was revisited by Brinster et al 27 in a prospective observational series of 18 patients who underwent elective hybrid MI-AVR and PCI from 2003 to 2006 In contrast to the prior study, PCI in this study was performed on either the same day or the evening prior to MI-AVR Notably, less than half of the patients (44%) required post-operative blood transfusions, likely due to the short time period between PCI and AVR, which did not allow for complete platelet inhibition from clopidogrel prior to the surgical intervention The results of this study were promising with only one early post-operative death due to colonic perforation and no late mortality up to 19 months More recently, in the largest study of combined valve surgery and PCI to date, Santana et al.28 studied 65 consecutive patients with CAD and either aortic (47.7%), mitral (36.9%), or combined aortic and mitral (15.4%) valvular disease who underwent planned PCI followed by valve surgery within 60 days This cohort was compared with 52 matched controls that underwent simultaneous CABG and conventional valve surgery The median number of days between PCI and valve surgery was 24 (interquartile range, 2.5 –37) There were no in-hospital deaths in the PCI group compared with two (3.8%) in the matched control group (P ¼ 0.11), and the combined endpoint of 30-day death, renal failure or stroke occurred in (1.5%) of the PCI group compared with 15 (28.8%) of the control group (P ¼ 0.001) Length of ICU and total hospital stay were less in the AVR/PCI group and the average amount of blood transfusions did not differ significantly between the groups While this study showed the potential promise of combined PCI and valvular surgery, it is important to note that it was a retrospective observational study of a heterogenous group of patients with follow-up J.M Paradis et al StudyAuthor Summary of the main studies on the ‘hybrid approach’ combining percutaneous coronary intervention and surgical aortic valve replacement Date of study Number Age LVEF of patients (years) (%) STS Logistic Indication score (%) Euroscore for PCI (%) Time between PCI and surgery Rate of DES Type of surgery implantation, % Rate of reoperation for bleeding, % Blood transfusion requirements Short-term Mid-long-term mortality mortality, % (In hospital-30 day mortality), % Byrne26 September 1997 – August 2003 Brinster27 Santana28 26 Median: Median: Median: 72 37 22 n/a UA ¼ 50% PCI days AMI ¼ 42% before Prior to complex (median) re-operative valve surgery ¼ 8% May 2003 to 18 February 2006 Median: Median: n/a 75 55 n/a n/a PCI ,24 h before February 2009 to June 2011 (study group) Historical control March 2005 – June 2011 Mean: Mean: n/a 75.4 53.9 10 n/a PCI 24 days before (median) 65 12 100 55.5 Re-operative valve surgery ¼ 42% (mitral ¼ pts, aortic ¼ pts) Primary valve surgery ¼ 58% (mitral ¼ 13 pts, aortic ¼ pt, double ¼ pt) Rate of any postoperative blood transfusions: 85% 3.8 MI-AVR Rate of any postoperative blood transfusions: 38.9% 5.5 (1 early post- 5.5 [at a mean operative follow-up of mortality 19 months form (no late a colonic mortalities)] perforation) MI-AVR 1.5 Mean number of transfusion:1.6 1, 3, year mortality was 22, 44, and 56, respectively Aortic stenosis and coronary artery disease Table n/a PCI, percutaneous coronary intervention; SAVR, surgical aortic valve replacement; LVEF, left-ventricular ejection fraction; STS, Society of Thoracic Surgeons; DES, drug eluting stent; n/a, not available; UA, unstable angina; AMI, acute myocardial infarction; pts, patients; MI-AVR, minimally invasive aortic valve replacement 2073 Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 2074 J.M Paradis et al SAVR) *For re-operative patients, the clopidogrel loading dose is given via the nasogastric tube at the time of aortic cross-clamping AS, aortic stenosis; TAVR, transcatheter aortic valve replacement; SAVR, surgical aortic valve replacement; CAD, coronary artery disease; CABG:, coronary artery bypass grafting; LAD, left-anterior descending coronary; PCI, percutaneous coronary intervention; OR, operating room analysed the impact of CAD requiring prior CABG or PCI in 201 highrisk patients undergoing TAVR (161 transfemoral and 40 transapical) In this study, patients with CAD had higher rates of important medical comorbidities, higher EuroSCORE (35.8 vs 26.1%), lower ejection fraction (EF) (48 vs 54%), and were more frequently treated by the TA access Overall mortality after TAVR was significantly higher among the CAD group (35.7 vs 18.4%), and logistic regression analysis found that patients with CAD were 10.1 times more likely to die (95% CI 2.1 –174.8) within 30 days of TAVR However, there was no indication in the analysis that a history of either CABG or PCI directly led to an increased risk of mortality Several limitations of this study are worth noting The study represents the earliest experience with TAVR in both the USA and Europe, and techniques and devices have since been refined Also, CAD was defined simply as prior revascularization (CABG or PCI), and there was no information about ischaemic burden or completeness of revascularization Finally, the populations were unmatched, and there were significant differences in terms of comorbidities and risk profiles, so it is possible that CAD in this study was simply a marker of higher risk patients rather than a cause of adverse outcomes In contrast, a study by Masson et al.,48 of 136 patients who underwent TAVR between 2005 and 2007, showed similar survival rates in quintiles stratified by the extent of CAD, as assessed by the Duke Myocardial Jeopardy Score (DMJS) The groups were similar with respect to baseline risk factors except for peripheral vascular disease, which was more common in the groups with higher DMJS The authors concluded that, in this cohort of patients, the presence of CAD or non-revascularized myocardium was not associated with an increased risk of adverse events However, the sample size of this study was small, and 15 patients underwent revascularization with PCI prior to TAVR, which may have impacted the results Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 Figure Algorithm used at Columbia University Medical Center to treat patients with severe aortic stenosis (PART 1: selected treatment option: Influence of coronary artery disease on outcomes after transcatheter aortic valve replacement Study-Author Date of study Study groups (n) Age (years) LVEF (%) Dewey20 December 2005 to February 2008 CAD ¼ 84 No CAD ¼ 87 CAD ¼ 83.9 CAD ¼ 47.6 No CAD ¼ 83.8 No CAD ¼ 53.7 Masson48 January Group A: no Overall ¼ 85.1 2005 to CAD (32) December Group B: CAD 2007 with DMJS (41) Group C: CAD with DMJS (28) Group D: CAD with DMJS (18) Group E: CAD with DMJS ≥6 (17) Gautier.49 October 2006 – October 2009 Ussia50 June 2007 – Dec 2009 STS score Definition of CAD In-hospital/30-day mortality, % Mid-long-term mortality Conclusion (1-year or at follow-up), % CAD ¼ 38.7 No CAD ¼ 29.3 Previous CABG or PCI Overall population ¼ 29.0 CAD ¼ 144 Overall ¼ 82.8 Overall ¼ 48 Overall ¼ 16 (TAVR ¼ 83) CAD ¼ 81.0 CAD ¼ 45 CAD ¼ 17 No CAD ¼ 86 No CAD ¼ 83.0 No CAD ¼ 53 No CAD ¼ 14 (TAVR ¼ 62) Overall ¼ 28 CAD ¼ 31 No CAD ¼ 24 CAD ¼ 251 No CAD ¼ 408 CAD group with Previous PCI or surgical CAD ¼ 6.0 critical stenosis revascularization No CAD ¼ 5.9 ¼ 25.4 (P ¼ 0.61) CAD group without critical stenosis ¼ 31.7 Limitations CAD ¼ 13.1 No CAD ¼ 1.2 (P ¼ 0.002) CAD ¼ 35.7 No CAD ¼ 18.4 (P ¼ 0.01) Coexisting coronary artery (i) CAD was defined disease negatively as prior impacts procedural revascularization outcomes and (CABG or PCI) with long-term survival in no information on patients undergoing ischaemic burden TAVR (ii) Results were confounded by the fact that patients with CAD were more likely to also have other important co-morbidities Median ¼ 60.0 Overall population ¼ 9.1 Presence of prior A ¼ 6.3 B ¼ 14.6 revascularization or C ¼ 7.1 D ¼ 5.6 E any coronary lesion ¼ 17.7 (P ¼ 0.56) of ≥50% in severity by visual assessment Stratified into groups based on DMJS 1-year mortality rates: A ¼ 18.8 B ¼ 28.8 C ¼ 35.7 D ¼ 11.1 E ¼ 29.4 (P ¼ 0.63) The presence of CAD or non-revascularized myocardium was not associated with an increased risk of adverse events History of prior MI CAD ¼ 10 or coronary No CAD ¼ 15 revascularization or (P ¼ 0.37) significant coronary stenosis on screening angiography (epicardial artery with ≥70% luminal diameter measured in the “worst view” angiographic projection or ≥50% for the left main stenosis) 1-year mortality rates: CAD ¼ 23.6 No CAD ¼ 29.4 (P ¼ 0.28) (i) CAD had a limited Inclusion of many impact on both subsets of patients decision to perform (i.e SAVR, TAVR, TAVR as well as both medical treatment short and mid-term only) prognosis (ii) It supported a selective revascularization strategy with only 17% of patients with new or residual CAD found on TAVR evaluation undergoing PCI CAD group n/a with critical stenosis ¼ 48.3 CAD group without critical 1-year mortality rates: CAD ¼ 14.5 No CAD ¼ 15.9 (P ¼ 0.33) Coexisting CAD does not CAD was defined impact procedural based on historical outcomes and revascularization mid-term incidence of and not based on MACCE and survival in the significance of elderly patients coronary stenosis at (i) Small sample size (ii) PCI performed prior to TAVR in 15 patients Continued Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 Overall ¼ 81.2 CAD ¼ 14.5 No CAD ¼ 9.7 2075 Logistic Euroscore Aortic stenosis and coronary artery disease Table 2076 Previous PCI or CABG Complete or 50% stenosis revascularization of an epicardial ¼ 6.5 artery based on Incomplete visual assessment revascularization ¼ 6.5 (P ¼ 99) Overall ¼ 17.63 Overall ¼ 50.5 n/a Overall ¼ 80.3 CAD ¼ 124 Van Mieghem52 November 2005 – June No CAD ¼ 88 2012 No CAD group with critical stenosis ¼ 22.2 No CAD group without critical stenosis ¼ 20.5 stenosis ¼ 47.2 No CAD group with critical stenosis ¼ 53.2 No CAD group without critical stenosis ¼ 53.1 LVEF, left-ventricular ejection fraction; STS, Society of Thoracic Surgeons; CAD, coronary artery disease; CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; TAVR, transcatheter aortic valve replacement; DMJS, Duke myocardial jeopardy score; SAVR, surgical aortic valve replacement; MACCE, major adverse cerebrovascular and cardiac events; MCV, medtronic corevalve 1-year mortality rates: Complete revascularization ¼ 21.1 Incomplete revascularization ¼ 22.6 (P ¼ 0.85) The study supported (i) Single centre study a selective (ii) Small sample size revascularization strategy based on a heart team consensus the time of procedure undergoing TAVR with MCV In-hospital/30-day mortality, % Definition of CAD Logistic Euroscore STS score LVEF (%) Age (years) Study groups (n) Study-Author Date of study Continued Table These results were supported by two prospective studies of the impact of CAD on AS in the TAVR era The first was published by Gautier et al 49 in 2011, in which 240 high-risk patients with severe AS were consecutively enrolled from 2006 to 2009 Of the 230 patients with known coronary status, 63% had CAD which was defined as a history of prior myocardial infarction, coronary revascularization, or significant angiographic coronary stenosis (epicardial artery with ≥70% diameter stenosis or left main ≥50%) Among the study population, 63% underwent TAVR, 13% underwent surgical AVR, and 24% were treated medically CAD did not lead to denial of intervention in any patient, and only one patient underwent surgical treatment due to CAD (unprotected left main stenosis) Among those with CAD who underwent TAVR, the decision to proceed with PCI was clinically driven and restricted to patients who presented with angina or had threatening ostial or proximal coronary lesions with a large area of myocardium at risk Of the 83 patients with CAD who underwent TAVR, 16 (19%) were found to be free of any residual significant coronary stenosis at evaluation for TAVR Among the remaining 67 patients with ≥1 coronary stenosis, 56 (83%) did not undergo revascularization prior to TAVR Survival rates were similar in the CAD and non-CAD groups at 30 days (90 vs 85%, P ¼ 0.37) and year (76 vs 71%, P ¼ 0.28) Functional status was also similar in both groups at year This study showed that CAD had limited impact on the decision to perform TAVR as well as the short- and mid-term prognosis It supported a selective revascularization strategy with only 17% of patients with new or residual CAD found on TAVR evaluation undergoing PCI This study was limited by a lack of long-term outcome data and the inclusion of many subsets of patients (i.e AVR, TAVR, medical treatment only) instead of a homogenous patient population The very small sample size of patients undergoing PCI prior to or concomitant with TAVR limits the ability of meaningful conclusions to be made about such strategies Recently, a meta-analysis of adjusted observational results of seven studies and 2472 patients also supported the finding that CAD does not affect TAVR outcomes after a median follow-up of 452 days.51 Indeed, in the multivariable analysis, the diagnosis of CAD had no influence on the risk of all cause death (OR 1.0, 95% CI: 0.67–1.50) The impact of a selective revascularization strategy on TAVR patients was further explored by Van Mieghem et al 52 in a singlecentre study of 263 consecutive patients who underwent TAVR from November 2005 to June 2012 Coronary angiography was performed in all patients, and significant CAD was defined as 50% stenosis of an epicardial artery based on visual assessment The treatment strategy and completeness of revascularization was decided by the heart team prior to the TAVR procedure, and CAD was managed using one of following treatment strategies: (i) staged PCI before TAVR; (ii) PCI concomitant with the TAVR procedure; (iii) no PCI For all patients without previous CABG (73%), including those with previous PCI (28%), the SYNTAX score was calculated both before and after the TAVR procedure For patients with a history of CABG, completeness of revascularization was assessed by evaluating both native coronary circulation and respective grafts The Medtronic Corevalve was the predominant device in the study (93.2%) Significant CAD was found in 124 patients (47%), of which 44 of these patients had a history of previous CABG The median preprocedure SYNTAX score of the patients without a history of Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 Mid-long-term mortality Conclusion (1-year or at follow-up), % Limitations J.M Paradis et al 2077 Aortic stenosis and coronary artery disease CABG was 9.00 (2.38–15.63) Staged PCI with a preference for DES was planned in 19 patients, and concomitant PCI and TAVR was performed in 20 patients The post-procedure median SYNTAX score was 5.00 (.13–9.88) Taken together, 99 patients (37%) (61 without CABG history and 38 with a CABG history) had incomplete revascularization after TAVR Furthermore, complete revascularization was only achieved in 20% of patients with incomplete revascularization at baseline Notably, revascularization status had no impact on survival or combined VARC endpoints during a median follow-up duration of 16 months Not only did this study support a selective revascularization strategy, it also demonstrated the feasibility of basing that strategy on heart team consensus Major limitations of this study include its single-centre design and relatively small sample size The largest series to date to examine the impact of CAD on TAVR outcomes was published from an Italian registry.50 This analysis included 663 consecutive patients who underwent TAVR with the Corevalve demonstrated that CAD, defined as prior PCI or CABG, had no impact on major adverse cerebrovascular and cardiac events (MACCE) (adjusted HR 0.76; 95% confidence interval 0.42–1.36; P ¼ 0.353) or all-cause mortality (adjusted HR 0.74; 95% CI 0.40–1.36; P ¼ 0.331) at a mean follow-up of 19 months However, a higher incidence of myocardial infarction (4.8%) was found in the group not undergoing any revascularization compared with the groups in which revascularization was complete (0.0%) or partial (1.8%) Limitations of this non-randomized study included the lack of specific tools, such as fractional flow reserve, intravascular ultrasound, quantitative coronary analysis, or myocardial jeopardy score, to assess the functional significance of coronary stenoses There were also differences in the TAVR experience among the participating centres and a lack of standardized outcomes definitions As a result of the limited number of studies examining the impact of CAD on outcomes of patients undergoing TAVR, there is no consensus on how to best manage concomitant CAD in these patients In some patients, medical treatment of CAD might be sufficient once TAVR eliminates the strain of severe aortic valve stenosis However, the TAVR procedure itself, which often generates hypotension and requires rapid ventricular pacing, may lead to increased myocardial ischaemia in patients with untreated CAD Conversely, treating CAD with PCI in patients with severe AS is not without significant risks from increased exposure to contrast and increased bleeding risk owing to the necessity of dual anti-platelet therapy Furthermore, if revascularization is desired in these patients, it is unclear whether a selective or complete revascularization strategy should be pursued Neither the most appropriate revascularization strategy nor the optimal timing for such interventions has yet to be determined sections below review the existing experience with different PCI timing strategies (Table 4) Timing of percutaneous coronary intervention in patients undergoing transcatheter aortic valve replacement Some authors have proposed performing PCI and TAVR during a single procedure.56,57 Potential advantages of this approach may include enhanced resource utilization, patient convenience, safety due to use of the same arterial access for both PCI and TAVR A small case series of 28 inoperable patients who underwent PCI and TAVR between 2008 and 2010 was the first to demonstrate that concomitant PCI and TAVR was feasible and safe.57 Twenty-one patients underwent staged PCI and TAVR, with PCI on average 14.3 days prior Percutaneous coronary intervention before TAVR in patients with significant CAD has the potential to reduce the procedural risk of TAVR as well as the need for revascularization after TAVR.25 Gasparetto et al 53 assessed the safety and efficacy of a selective percutaneous revascularization strategy before TAVR This single-centre, prospective registry (PUREVALVE Registry) included 191 consecutive patients with severe AS referred for TAVR The presence of CAD was defined as any previous percutaneous or surgical coronary revascularization or the presence of any coronary stenosis of at least 50% Percutaneous coronary intervention was performed only for lesions involving proximal-to-mid segments of major coronary branches Chronic total occlusions (CTO) and lesions in small vessels (reference diameters ,2.5 mm) were not considered for revascularization Interventions were performed only on lesions that were deemed clinically relevant after consideration of symptoms, the extent of myocardium at risk, proven ischaemia by invasive or non-invasive testing, and technical feasibility of 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%) A total of 78 stents were implanted in 66 lesions and BMSs were used in 56.4% of cases Overall 30-day mortality did not differ significantly between patients with or without CAD (5.7 vs 2.9%, P ¼ 0.32), although there were numerically higher rates of myocardial infarction (4.4 vs 0%, P ¼ 0.08) and major stroke (2.7 vs 0%, P ¼ 0.14) in the CAD group These results suggest that a selective, clinically driven coronary revascularization strategy before TAVR can lead to outcomes similar to those observed in patients without CAD In another study by Abdel-Wahab et al.,54 55 patients who underwent PCI before TAVR with the Medtronic CoreValve prosthesis were compared with 70 patients who underwent TAVR alone Thirty-day mortality, major bleeding, major vascular complications, VARC defined combined safety endpoint, symptom improvement, and adverse events at months were comparable between the two groups, again suggesting that PCI before TAVR is safe and effective In another single-centre study, TAVR combined with PCI within 12 months produced at least equivalent results for in-hospital mortality in 59 high-risk patients presenting with AS and concomitant CAD compared with 184 high-risk patients undergoing SAVR and CABG surgery.55 Concomitant with transcatheter aortic valve replacement Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 Similar to revascularization strategies, the optimal timing of revascularization remains uncertain in patients undergoing TAVR The Before transcatheter aortic valve replacement Study 2078 Table Summary of the main studies on percutaneous coronary intervention and transcatheter aortic valve replacement Study groups (n) Study type/ patient population Definition of CAD Decision to perform PCI Characteristics BMS vs of intervention DES, % Anatomically Antiplatelet Followup therapy complete revascularization (definition, % of cohort obtained) 30-day outcomes Mid/ Long-term Outcomes Conclusions Prior to TAVR Gasparetto53 Total population: Single-centre 191 patients, prospective 113 pts with registry CAD Wendt55 n/a Group 1: PCI 14 days prior to procedure (on average) Group 2: PCI performed immediately before TAVR BMS: 65.9 n/a All patients 30 days received a loading dose of 300 mg of Clopidogrel either before the initial PCI in the staged approach or before the combined single-stage (i) PCI was Overall mortality A selective strategy performed at follow-up of treating CAD prior to TAVR in was 14.8% with PCI prior to 29.4% of without TAVR is safe and patients with no significant has short- and adverse events differences mid-term (ii) All-cause between CAD outcomes similar mortality was and non-CAD to patients 4.2% and groups without CAD cardiovascular mortality was 3.7%, with no difference between CAD and non-CAD patients All-cause mortality: All-cause mortality PCI before TAVR PCI + TAVR: 2% at up to years: appears feasible Isolated TAVR: 6% PCI + TAVR: 8.1% and safe (P ¼ 0.27) Isolated TAVR: 16.1% (P ¼ 0.36) 30-day mortality Freedom from PCI (within 12 was similar in cardiac months) and the two groups: reintervention TAVR produce 12.5% in Group was similar in similar results for compared the two groups in-hospital with 11.5% in mortality Group compared with high-risk patients undergoing SAVR + CABG (i) No n/a periprocedural MI, or stroke in any patient (ii) Overall in-hospital and 30-day mortality was identical at 7.1% (n ¼ of 28) (iii) The two deaths occurred in Group (periprocedural Concomitant PCI and TAVR procedure is feasible and safe Higher risk of renal failure with the concomittant strategy J.M Paradis et al PCI concomitant with TAVR Total population: Retrospective n/a Conradi57 28 patients single-centre Group : PCI study prior to TAVR (21 patients) Group 2: PCI concomittant with TAVR (7 patients) Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 AbdelWahab54 Driven first by Previous PCI or PCI performed BMS: 56.4 Defined as ASA 100 mg, 12.9 surgical symptoms, then 27 days prior complete months Clopidogrel coronary evaluation of to PCI revascularization 75 mg for revascularization the extent of (median) of all stenotic months and/or presence myocardium coronary vessels after TAVR of any coronary at risk, ≥2.5 mm, 33.6 for patients stenosis of at non-invasive/ with BMS least 50% in invasive tests, and 12 diameter of the technical months for epicardial feasibility of PCI patients coronary CTO and lesions with DES arteries by visual in small vessels assessment (reference diameter ,2.5 mm) were not considered for revascularizaton PCI+TAVR: Single-centre Presence of lesions All significant PCI performed DES: 71 n/a n/a Up to 55 patients retrospective with ≥50% (.50%) lesions 10 days before BMS: 24 years Isolated TAVR: study diameter in the major TAVR (median) DES and BMS: 70 patients stenosis on epicardial angiogram and/ coronary vessels or previous MI, PCI, or CABG Group 1: SAVR Non n/a The indication for PCI performed BMS: 70 n/a n/a Up to and CABG: randomized, PCI was 82+/293 days DES: 30 years 184 patients single-centre discussed in a before TAVR Group 2: PCI + study consensus TAVR: 59 conference patients (heart team) Wenaweser56 Total population: Prospective History of PCI Operators used Staged PCI Group 1: 47.8% DMJS ,1, 49 256 pts single-centre or CABG or DMJS and performed at of BMS Group 1: PCI registry stenosis of SYNTAX score 34 + 26 days of Group 2: 11.4% prior to TAVR 50 % in at least CTO and distal TAVR of BMS (23 pts) one coronary segments or side Concomitant Group 2: PCI artery during branches with a PCI performed with coronary small area at risk immediately concomitant angiography were left before TAVR TAVR (36 pts) untreated Group 3: TAVR alone (197 pts) prosthesis embolization, asystolic arrest on POD 5) For pts Up to Clinical outcomes No difference (i) Staged or undergoing years at 30 days were between concomitant PCI PCI + similar for overall are both safe and TAVR: patients mortality in feasible Aspirin at undergoing patients with or treatment least isolated TAVR without CAD options in select 100 mg compared with up to 2-year patients daily, TAVR follow-up undergoing 600 mg combined with TAVR plavix load PCI in terms of (ii) Complete or prior to PCI death (5.6 vs incomplete 10.2%, revascularization P ¼ 0.24), does not appear major stroke to adversely (4.1 vs 3.4%, impact mid-term P ¼ 1.00), and survival combined safety endpoint from the VARC (31.0 vs 23.7%, P ¼ 0.33) Aortic stenosis and coronary artery disease procedure in addition to Aspirin PCI after TAVR Pasic60 Total population Retrospective Only significant 419 subjects single-centre CAD was with 46 study reported patients undergoing PCI immediately after the TA-TAVR (i) LM 50% PCI performed n/a (ii) Coronary immediately stenosis of after TA-TAVR ≥90% in the proximal or mid-LAD or proximal or mid RCA (if right dominant) or proximal or mid left circumflex (if dominant) (iii) The coronary lesions above were amendable to straightforward PCI with a very high probability of success n/a ASA 100 mg, years clopidogrel 75 mg daily for at least months Patients undergoing combined PCI and TAVR received additional loading dose of 300 mg of clopidogrel (i) Technical In the TA-TAVR Simultaneous treatment of the procedural and PCI group, most significant success was survival at 12, CAD with PCI achieved in 24, and 36 immediately 100% of months was after TA-TAVR is patients, 87.1, 69.7, and safe and feasible without any 69.7%, need for respectively conversion to open heart surgery (ii) 30 day mortality rate was 4.3% PCI, percutaneous coronary intervention; TAVR, transcatheter aortic valve replacement; BMS, bare metal stent; DES, drug-eluting stent; CAD, coronary artery disease; CTO, chronic total occlusion; MI, myocardial infarction; CABG, coronary artery bypass grafting; DMJS, Duke myocardial jeopardy score; VARC, valve academic research consortium; TA, trans-apical; LM, left main; LAD, left anterior descending coronary; RCA, right coronary artery; pts, patients 2079 Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 2080 J.M Paradis et al Table Unanswered questions regarding the management and the impact of coronary artery disease in patients with severe aortic stenosis – Will the extent of CAD impact post-TAVR symptoms or long-term survival? – Can TAVR be performed safely in the setting of various degrees of CAD? – When PCI is deemed appropriate, what is the optimal timing to proceed with coronary revascularization? – Is a single-stage or multi-stage procedure preferred? – Since the transcatheter technology is focusing on younger and lower-risk patients and since surgeons generally aim for complete revascularization during surgical AVR, should this be a prerequisite for transcatheter approaches? – Are patients with AS and a high SYNTAX score better suited for surgical AVR and CABG than TAVR and PCI, provided that they are reasonable surgical candidates? – Will the use of antiplatelet agents impact bleeding complications after TAVR, especially via the trans-apical approach, and should this impact the decision to use BMS or DES during PCI? – Should balloon aortic valvuloplasty be performed before PCI to mitigate the risk of PCI in the setting of AS, especially in patients with depressed LV function? – As TAVR is performed in lower-risk patients with better long-term prognosis independent of the AS, will the threshold for treating CAD become lower because the potential impact of CAD on long-term mortality and quality of life will be greater? CAD, coronary artery disease; TAVR, transcatheter aortic valve replacement; PCI, percutaneous coronary intervention; AS, aortic stenosis; AVR, aortic valve replacement; CABG, coronary artery bypass grafting; BMS, bare metal stent; DES, drug eluting stent After transcatheter aortic valve replacement Investigators have also explored the possibility of performing PCI immediately after TAVR, but this strategy poses certain, unique procedural risks.58,59 These include the possibility that the prosthetic valve struts may interfere with cannulation of the coronary arteries and that catheter manipulation may potentially dislodge the prosthetic valve.25 Pasic et al.60 analysed the outcomes of 419 patients who underwent TA TAVR between 2008 and 2011 In this cohort, single-stage PCI was performed immediately after TAVR in 46 patients (11%) Only the most significant lesions that were amenable to straightforward PCI were treated Technical procedural success was achieved in 100% of patients, without any need for conversion to open surgery In the TA-TAVR and PCI group, survival at 12, 24, and 36 months was 87.1, 69.7, and 69.7% respectively The authors’ rationale for this approach was the view that severe AS could be viewed as the ‘most proximal coronary artery stenosis’ and treating AS with TAVR would decrease myocardial oxygen demand, leaving the patient less vulnerable to possible intra-procedural complications of PCI While this study demonstrated that this single-stage approach may be feasible and safe at least for selected patients undergoing TA-TAVR, it remains unclear if these findings will be broadly applicable Unanswered questions In the TAVR era, there remain more questions than answers with respect to CAD and AS The only randomized study in the literature, the Placement of AoRTic TraNscathetER Valves (PARTNER) trial, excluded patients with unrevascularized, obstructive CAD and did not demonstrate any interaction between CAD or prior coronary revascularization and mortality.30 Robust data are still lacking on numerous aspects regarding both the management and the impact of CAD in patients with AS Table summarizes some of the unanswered questions Further studies are needed to address some of these issues Indeed, no large studies have demonstrated the superiority of one type of stent over the other in patients undergoing PCI and TAVR Therefore, taking into account the risk of bleeding as well as the risk of restenosis, the decision to implant a BMS or DES should be individualized by the heart team The access route might also have an influence on the type of stent selected by the heart team since the longer mandatory dual antiplatelet therapy with DES may increase the bleeding risk for patients scheduled for an approach other than transfemoral TAVR Larger trials will also be needed to resolve the matters of the best antithrombotic/antiplatelet regimen for patients undergoing PCI and TAVR, as well as the concern of the impact of those procedures on the quality of life.61 Upcoming studies PARTNER 2A and SURTAVI (Surgical Replacement and Transcatheter Aortic Valve Implantation) are large, randomized, controlled Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 to TAVR, while seven were treated in a single procedure In this small retrospective study, the overall 30-day mortality was 7.1%, which is comparable to the rates reported in multiples studies and registries The question of feasibility and safety of concomitant PCI and TAVR was further addressed by a study of the BERN TAVI registry,56 which prospectively enrolled 256 patients undergoing TAVR In this study, CAD was defined as an angiographic stenosis of 50% in at least one coronary artery or a history of PCI or CABG In patients with CAD, the amount of myocardium at risk was assessed using the DMJS Of the 165 patients with CAD, 59 underwent PCI either prior to TAVR (n ¼ 23) or in a single-stage procedure (n ¼ 36) Of the remaining 108 patients with CAD, 53 had been completely revascularized prior to TAVR, and 55 had an incomplete revascularization status (DMJS ≥1) In this study, CTO and distal segments or side branches with a small area at risk were left untreated Clinical outcomes at 30 days were similar for patients undergoing isolated TAVR or concomitant TAVR and PCI in terms of death (5.6 vs 10.2%, P ¼ 0.24), major stroke (4.1 vs 3.4%, P ¼ 1.00), and VARC combined safety endpoint (31.0 vs 23.7%, P ¼ 0.33) Limitations of this study include its observational nature, the limited number of patients, and the possibility of selection bias (the treatment strategy was left to the discretion of the operator) Nevertheless, it appears to demonstrate that revascularization with PCI can be safely performed either before TAVR or as a single-stage procedure with TAVR 2081 Aortic stenosis and coronary artery disease trials that will include patients with CAD requiring revascularization and will compare AVR with and without CABG vs TAVR with and without PCI PARTNER 2A trial The PARTNER 2A trial is a prospective, multicentre, randomized trial comparing safety and efficacy of SAVR vs TAVR with the Edwards SAPIEN XT THV with NovaFlex delivery system in intermediate risk surgical candidates Enrolment will consist of up to 2000 patients at intermediate risk for surgical AVR The study excludes patients with complex coronary disease, defined as an unprotected left main lesion or a SYNTAX score 32 However, patients with CAD that requires revascularization are randomized to undergo TAVR and PCI or SAVR and CABG with the exact timing of the PCI left to operator discretion SURTAVI trial ACTIVATION trial The percutAneous Coronary inTerventIon prior to transcatheter aortic VAlve implantaTION: a randomized controlled trial (ACTIVATION), will be the first randomized trial to specifically address the impact of coronary revascularization by PCI for significant CAD prior to TAVR This study will be conducted at a number of European centres and will randomize 310 patients with severe AS and at least one proximal coronary stenosis of ≥70% to undergo PCI and TAVR vs TAVR alone Important endpoints will include 30-day and 1-year mortality and re-hospitalization Hopefully, from these studies, a clearer understanding of the best PCI strategy in various clinical scenarios will emerge Until then, a case Figure Algorithm used at Columbia University Medical Center to treat patients with severe aortic stenosis (PART 2: selected treatment option: TAVR) AS, aortic stenosis; TAVR, transcatheter aortic valve replacement; SAVR, surgical aortic valve replacement; CAD, coronary artery disease; CTO, chronic total occlusion; LM, left main; pLAD, proximal left-anterior descending artery; CABG, coronary artery bypass grafting; PCI, percutaneous coronary intervention; BAV, balloon aortic valvuloplasty; pLVAD, percutaneous left-ventricular assist device; IABP, intra-aortic balloon pump; BMS, bare metal stent; DES, drug eluting stent Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 The Medtronic CoreValvew SUrgical Replacement And Transcatheter Aortic Valve Implantation (SURTAVI) trial is a prospective, multicentre, randomized trial comparing safety and efficacy of SAVR vs TAVR with the Medtronic CoreValve System in intermediate risk surgical candidates (STS score ≥4% and ≤10%) Every patient undergoes a heart team evaluation, which includes an assessment for significant CAD and the need for revascularization If there is significant CAD with intended revascularization, the patient is then randomized and will undergo either TAVR + PCI or SAVR + CABG If there is no intended revascularization, the patient is randomized between TAVR only or SAVR only Up to 2500 patients will be included in the trial and followed through years Clinical endpoints will be reported and adjudicated according to Valve Academic Research Consortium (VARC) standard endpoint definitions 2082 Conclusion For many decades, surgical aortic valve replacement has been considered the standard treatment for symptomatic severe AS The high prevalence of CAD in this patient population has been well documented and was classically treated in a combined AVR/CABG procedure With TAVR emerging as a reasonable alternative for patients deemed inoperable or at high risk for surgery, the question of how to manage concomitant CAD is currently being revisited Recent studies point to a treatment paradigm shift from SAVR and CABG to TAVR and PCI or even a hybrid approach However, the lack of robust randomized data is striking and many questions remain unanswered Ongoing studies, like PARTNER 2A and SURTAVI, will analyse the outcomes of TAVR in lower risk populations, and will scrutinize the impact of percutaneous or surgical revascularization strategies In this context, while awaiting more definitive data, the collaborative efforts of the heart team remain crucial to appropriately managing and optimizing the outcomes of patients with AS and CAD Conflicts of interest: M.W and S.K have received consulting fees from Edwards Lifesciences M.B.L is a non-paid member of the Scientific Advisory Board of Edwards Lifesciences and Medtronic Vascular The other authors not have any disclosures References Rapp AH, Hillis LD, Lange RA, Cigarroa JE Prevalence of coronary artery disease in patients with aortic stenosis with and without angina pectoris Am J Cardiol 2001;87: 1216 –1217 Vandeplas A, Willems JL, Piessens J, De Geest H Frequency of angina pectoris and coronary artery disease in severe isolated valvular aortic stenosis Am J Cardiol 1988;62:117 –120 Pibarot P, Dumesnil JG Improving assessment of aortic stenosis J Am Coll Cardiol 2012;60:169 –180 Stewart BF, Siscovick D, Lind BK, Gardin JM, Gottdiener JS, Smith VE, Kitzman DW, Otto CM Clinical factors associated with calcific aortic valve disease Cardiovascular Health Study J Am Coll Cardiol 1997;29:630 –634 Iung B Interface between valve disease and ischaemic heart disease Heart 2000;84: 347 –352 Adler Y, Vaturi M, Herz I, Iakobishvili Z, Toaf J, Fink N, Battler A, Sagie A Nonobstructive aortic valve calcification: a window to significant coronary artery disease Atherosclerosis 2002;161:193 197 Kvidal P, Bergstroăm R, Hoărte LG, Stahle E Observed and relative survival after aortic valve replacement J Am Coll Cardiol 2000;35:747 – 756 Roberts WC Morphologic features of the normal and abnormal mitral valve Am J Cardiol 1983;51:1005 –1028 Thubrikar MJ, Deck JD, Aouad J, Chen JM Intramural stress as a causative factor in atherosclerotic lesions of the aortic valve Atherosclerosis 1985;55:299 –311 10 Garcia D, Camici PG, Durand L-G, Rajappan K, Gaillard E, Rimoldi OE, Pibarot P Impairment of coronary flow reserve in aortic stenosis J Appl Physiol 2009;106: 113 –121 11 Rajappan K, Rimoldi OE, Dutka DP, Ariff B, Pennell DJ, Sheridan DJ, Camici PG Mechanisms of coronary microcirculatory dysfunction in patients with aortic stenosis and angiographically normal coronary arteries Circulation 2002;105:470 –476 12 Bartel T, Yang Y, Muăller S, Wenzel RR, Baumgart D, Philipp T, Erbel R Noninvasive assessment of microvascular function in arterial hypertension by transthoracic Doppler harmonic echocardiography J Am Coll Cardiol 2002;39:2012 –2018 13 Tonino PAL, De Bruyne B, Pijls NHJ, Siebert U, Ikeno F, van’ t Veer M, Klauss V, Manoharan G, Engstrøm T, Oldroyd KG, Ver Lee PN, Maccarthy PA, Fearon WF FAME Study Investigators Fractional flow reserve versus angiography for guiding percutaneous coronary intervention N Engl J Med 2009;360:213 –224 14 Stefanini GG, Stortecky S, Meier B, Windecker S, Wenaweser P Severe aortic stenosis and coronary artery disease EuroIntervention 2013;9:63 68 15 Staăhli BE, Maier W, Corti R, Luăscher TF, Altwegg LA Fractional flow reserve evaluation in patients considered for transfemoral transcatheter aortic valve implantation: a case series Cardiology 2012;123:234 –239 16 Demirkol MO, Yaymacı B, Debes¸ H, Bas¸aran Y, Turan F Dipyridamole myocardial perfusion tomography in patients with severe aortic stenosis Cardiology 2002;97: 37 –42 17 Julius BK, Spillmann M, Vassalli G, Villari B, Eberli FR, Hess OM Angina pectoris in patients with aortic stenosis and normal coronary arteries Mechanisms and pathophysiological concepts Circulation 1997;95:892 – 898 18 Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP, Guyton RA, O’Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM, Thomas JD 2014 AHA/ACC Guideline for the Management of Patients With Valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines J Am Coll Cardiol 2014;14:735 –1097 19 Aranki S, Rizzo R, Couper G, Adams D, Collins J, Gildea J, Kinchla N, Cohn L Aortic valve replacement in the elderly: effect of gender and coronary artery disease on operative mortality Circulation 1992;88:17– 23 20 Dewey TM, Brown DL, Herbert MA, Culica D, Smith CR, Leon MB, Svensson LG, Tuzcu M, Webb JG, Cribier A, Mack MJ Effect of concomitant coronary artery disease on procedural and late outcomes of transcatheter aortic valve implantation Ann Thorac Surg 2010;89:758–767 21 Vahanian A, Baumgartner H, Bax J, Butchart E, Dion R, Filippatos G, Flachskampf F, Hall R, Iung B, Kasprzak J, Nataf P, Tornos P, Torracca L, Wenink A Task Force on the Management of Valvular Hearth Disease of the European Society of Cardiology, ESC Committee for Practice Guidelines Guidelines on the management of valvular Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 by case approach should be used by the heart team to guide selection of patients for percutaneous revascularization prior to TAVR The risks and benefits of performing TAVR in the presence of unrevascularized CAD should be weighed against the risk-benefit ratio of doing a PCI prior to TAVR Figure shows the algorithm used in our high volume TAVR centre In our algorithm, as it is the case for the PARTNER 2A trial and for the SURTAVI study, the heart team (consisting of at least one interventional cardiologist and at least one cardiac surgeon) has to agree on a treatment strategy for AS and also for concomitant coronary disease During the initial evaluation, if the coronary disease is diffuse and complex, we tend to favour a surgical approach Although there is no established cut-off, the SYNTAX score should be calculated to guide the decision-making process For example, in the PARTNER2A and the SURTAVI trials, patients were excluded if their SYNTAX score was 32 and 22, respectively At Columbia University Medical Center, lesions located in small vessels, distal lesions, chronic total occlusions, or very complex lesions that will require a large iodine load for the PCI in patients with severe chronic renal failure all tend to be treated medically Moreover, it is important to mention that in the PARTNER 2A and the SURTAVI trials, patients with unprotected left main coronary disease are excluded However, in our centre, those left main cases are carefully reviewed but may still be considered for a left main PCI followed by a TAVR, especially if the coronary disease is located at the ostium of the left main Furthermore, in patients selected for a TAVR approach, our tendency is to proceed with a PCI prior to TAVR if the lesion is located in a vessel perfusing a significant territory, if the initial mode of presentation is an acute coronary syndrome (especially with dynamic ST changes or with hemodynamic instability), or if there is clinical evidence of ischaemia (for example, a positive stress-echocardiogram or a nuclear stress test showing significant ischaemia in the territory of the index lesion) To minimize the iodine contrast load and reduce the risk of acute kidney injury in patients with impaired renal function, we usually favour proceeding with PCI a few weeks before TAVR Prior to PCI, a right heart catheterization is nearly always performed Depending on the filling pressures and the complexity of the coronary intervention, we then consider the following options: (ii) performing a balloon aortic valvuloplasty; (ii) placing an intra-aortic balloon pump; or (iii) placing a leftventricular assist device As previously mentioned, the decision to implant a BMS or a DES should also be individualized J.M Paradis et al 2082a Aortic stenosis and coronary artery disease 22 23 24 25 26 27 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 Dancea A, Lachapelle K, Cheema A, Latter D, Horlick E Transcatheter aortic valve implantation for the treatment of severe symptomatic aortic stenosis in patients at very high or prohibitive surgical risk J Am Coll Cardiol 2010;55: 1080 – 1090 Wenaweser P, Pilgrim T, Kadner A, Huber C, Stortecky S, Buellesfeld L, Khattab AA, Meuli F, Roth N, Eberle B, Erdoăs G, Brinks H, Kalesan B, Meier B, Juăni P, Carrel T, Windecker S Clinical outcomes of patients with severe aortic stenosis at increased surgical risk according to treatment modality J Am Coll Cardiol 2011;58:2151 –2162 Walther T, Kasimir MT, Doss M, Schuler G, Simon P, Schaăchinger V, Mohr FW, Wimmer-Greinecker G One-year interim follow-up results of the TRAVERCE trial: the initial feasibility study for trans-apical aortic-valve implantation Eur J Cardiothorac Surg 2011;39:532 – 537 Petronio AS, De Carlo M, Bedogni F, Maisano F, Ettori F, Klugmann S, Poli A, Marzocchi A, Santoro G, Napodano M, Ussia GP, Giannini C, Brambilla N, Colombo A 2-year results of CoreValve implantation through the subclavian access: a propensity-matched comparison with the femoral access J Am Coll Cardiol 2012;60:502 – 507 Grube E, Buellesfeld L, Mueller R, Sauren B, Zickmann B, Nair D, Beucher H, Felderhoff T, Iversen S, Gerckens U Progress and current status of percutaneous aortic valve replacement: results of three device generations of the CoreValve Revalving system Circ Cardiovasc Interv 2008;1:167–175 Lefe`vre T, Kappetein AP, Wolner E, Nataf P, Thomas M, Schaăchinger V, De Bruyne B, Eltchaninoff H, Thielmann M, Himbert D, Romano M, Serruys P WimmerGreinecker G, PARTNER EU Investigator Group One year follow-up of the multicentre European PARTNER transcatheter heart valve study Eur Heart J 2011;32: 148 –157 Himbert D, Descoutures F, Al-Attar N, Iung B, Ducrocq G, De´taint D, Brochet E, Messika-Zeitoun D, Francis F, Ibrahim H, Nataf P, Vahanian A Results of transfemoral or transapical aortic valve implantation following a uniform assessment in high-risk patients with aortic stenosis J Am Coll Cardiol 2009;54:303 –311 Svensson LG, Dewey T, Kapadia S, Roselli EE, Stewart A, Williams M, Anderson WN, Brown D, Leon M, Lytle B, Moses J, Mack M, Tuzcu M, Smith C United States feasibility study of transcatheter insertion of a stented aortic valve by the left ventricular apex Ann Thorac Surg 2008;86:46 –54 Vahanian A, Alfieri OR, Al-Attar N, Antunes MJ, Bax J, Cormier B, Cribier A, de Jaegere P, Fournial G, Kappetein A-P, Kovac J, Ludgate S, Maisano F, Moat N, Mohr FW, Nataf P, Pierard L, Pomar JL, Schofer J, Tornos P, Tuzcu M, van Hout B, Segesser von LK, Walther T Transcatheter valve implantation for patients with aortic stenosis: a position statement from the European Association of Cardio-Thoracic Surgery (EACTS) and the European Society of Cardiology (ESC), in collaboration with the European Association of Percutaneous Cardiovascular Interventions (EAPCI) Eur J Cardiothorac Surg 2008;34:1 –8 Rode´s-Cabau J, Gutie´rrez M, Bagur R, De Larochellie`re R, Doyle D, Coˆte´ M, Villeneuve J, Bertrand OF, Larose E, Manazzoni J, Pibarot P, Dumont E Incidence, predictive factors, and prognostic value of myocardial injury following uncomplicated transcatheter aortic valve implantation J Am Coll Cardiol 2011;57:1988 –1999 Masson JB, Lee M, Boone RH, Ali Al A, Bugami Al S, Hamburger J, John Mancini GB, Ye J, Cheung A, Humphries KH, Wood D, Nietlispach F, Webb JG Impact of coronary artery disease on outcomes after transcatheter aortic valve implantation Catheter Cardiovasc Interv 2010;76:165 –173 Gautier M, Pepin M, Himbert D, Ducrocq G, Lung B, Dilly MP, Attias D, Nataf P, Vahanian A Impact of coronary artery disease on indications for transcatheter aortic valve implantation and on procedural outcomes EuroIntervention 2011;7: 549 –555 Ussia GP, Barbanti M, Colombo A, Tarantini G, Petronio AS, Ettori F, Ramondo A, Santoro G, Klugmann S, Bedogni F, Antoniucci D, Maisano F, Marzocchi A, Poli A, De Carlo M, Fiorina C, De Marco F, Napodano M, Violini R, Bortone AS, Tamburino C on behalf of CoreValve Italian Registry Investigators Impact of coronary artery disease in elderly patients undergoing transcatheter aortic valve implantation: Insight from the Italian CoreValve Registry Int J Cardiol 2013;167:943 – 950 D’Ascenzo F, Conrotto F, Giordana F, Moretti C, D’Amico M, Salizzoni S, Omede` P, La Torre M, Thomas M, Khawaja Z, Hildick-Smith D, Ussia G, Barbanti M, Tamburino C, Webb J, Schnabel RB, Seiffert M, Wilde S, Treede H, Gasparetto V, Napodano M, Tarantini G, Presbitero P, Mennuni M, Rossi ML, Gasparini M, Biondi-Zoccai G, Lupo M, Rinaldi M, Gaita F, Marra S Mid-term prognostic value of coronary artery disease in patients undergoing transcatheter aortic valve implantation: a meta-analysis of adjusted observational results Int J Cardiol 2013;168: 2528 –2532 Van Mieghem NM, Van der Boon RM, Faqiri E, Diletti R, Schultz C, van Geuns R-J, Serruys PW, Kappetein A-P, van Domburg RT, de Jaegere PP Complete revascularization is not a prerequisite for success in current transcatheter aortic valve implantation practice JACC Cardiovasc Interv 2013;6:867 –875 Gasparetto V, Fraccaro C, Tarantini G, Buja P, D’Onofrio A, Yzeiraj E, Pittarello D, Isabella G, Gerosa G, Iliceto S, Napodano M Safety and effectiveness of a selective Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 28 heart disease (version 2012): the Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) Eur Heart J 2012;33:2451 –2496 Tjang YS, Korfer R, Grobbee DE Predictors of mortality after aortic valve replacement Eur J Cardiothorac Surg 2007;32:469 –474 Hannan E, Wu C, Bennett E, Carlson R, Culliford A, Gold J, Higgins R, Smith C, Jones R Risk index for predicting in-hospital mortality for cardiac valve surgery Ann Thorac Surg 2007;83:921 – 929 Beach JM, Mihaljevic T, Svensson LG, Rajeswaran J, Marwick T, Griffin B, Johnston DR, Sabik JF III, Blackstone EH Coronary artery disease and outcomes of aortic valve replacement for severe aortic stenosis J Am Coll Cardiol 2013;61:837–848 Goel SS, Agarwal S, Tuzcu EM, Ellis SG, Svensson LG, Zaman T, Bajaj N, Joseph L, Patel NS, Aksoy O, Stewart WJ, Griffin BP, Kapadia SR Percutaneous coronary intervention in patients with severe aortic stenosis: implications for transcatheter aortic valve replacement Circulation 2012;125:1005 –1013 Byrne JG, Leacche M, Unic D, Rawn JD, Simon DI, Rogers CD, Cohn LH Staged initial percutaneous coronary intervention followed by valve surgery (‘hybrid approach’) for patients with complex coronary and valve disease J Am Coll Cardiol 2005;45:14–18 Brinster DR, Byrne M, Rogers CD, Baim DS, Simon DI, Couper GS, Cohn LH Effectiveness of same day percutaneous coronary intervention followed by minimally invasive aortic valve replacement for aortic stenosis and moderate coronary disease (‘hybrid approach’) Am J Cardiol 2006;98:1501 –1503 Santana O, Funk M, Zamora C, Escolar E, Lamas GA, Lamelas J Staged percutaneous coronary intervention and minimally invasive valve surgery: results of a hybrid approach to concomitant coronary and valvular disease J Thorac Cardiovasc Surg 2012;144:634 –639 Iung B, Baron G, Butchart EG, Delahaye F, Gohlke-Baărwolf C, Levang OW, Tornos P, Vanoverschelde J-L, Vermeer F, Boersma E, Ravaud P, Vahanian A A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease Eur Heart J 2003;24:1231 –1243 Leon MB, Smith CR, Mack M, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Brown DL, Block PC, Guyton RA, Pichard AD, Bavaria JE, Herrmann HC, Douglas PS, Petersen JL, Akin JJ, Anderson WN, Wang D, Pocock S PARTNER Trial Investigators Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery N Engl J Med 2010;363:1597 – 1607 Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, Tuzcu EM, Webb JG, Fontana GP, Makkar RR, Williams M, Dewey T, Kapadia S, Babaliaros V, Thourani VH, Corso P, Pichard AD, Bavaria JE, Herrmann HC, Akin JJ, Anderson WN, Wang D, Pocock SJ PARTNER Trial Investigators Transcatheter versus surgical aortic-valve replacement in high-risk patients N Engl J Med 2011; 364:2187 –2198 Gilard M, Eltchaninoff H, Iung B Registry of transcatheter aortic-valve implantation in high-risk patients N Engl J Med 2012;366:1705 –1715 Zahn R, Gerckens U, Linke A, Sievert H, Kahlert P, Hambrecht R, Sack S, Abdel-Wahab M, Hoffmann E, Schiele R, Schneider S, Senges J German Transcatheter Aortic Valve Interventions Registry Investigators Predictors of one-year mortality after transcatheter aortic valve implantation for severe symptomatic aortic stenosis Am J Cardiol 2013;112:272 –279 Thomas M, Schymik G, Walther T, Himbert D, Lefe`vre T, Treede H, Eggebrecht H, Rubino P, Colombo A, Lange R, Schwarz RR, Wendler O One-year outcomes of cohort in the Edwards SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) registry: the European registry of transcatheter aortic valve implantation using the Edwards SAPIEN valve Circulation 2011;124:425 – 433 Moat NE, Ludman P, de Belder MA, Bridgewater B, Cunningham AD, Young CP, Thomas M, Kovac J, Spyt T, MacCarthy PA, Wendler O, Hildick-Smith D, Davies SW, Trivedi U, Blackman DJ, Levy RD, Brecker SJ, Baumbach A, Daniel T, Gray H, Mullen MJ Long-term outcomes after transcatheter aortic valve implantation in high-risk patients with severe aortic stenosis: the U.K TAVI (United Kingdom Transcatheter Aortic Valve Implantation) Registry J Am Coll Cardiol 2011;58:2130 –2138 Tamburino C, Capodanno D, Ramondo A, Petronio AS, Ettori F, Santoro G, Klugmann S, Bedogni F, Maisano F, Marzocchi A, Poli A, Antoniucci D, Napodano M, De Carlo M, Fiorina C, Ussia GP Incidence and predictors of early and late mortality after transcatheter aortic valve implantation in 663 patients with severe aortic stenosis Circulation 2011;123:299 – 308 Piazza N, Grube E, Gerckens U, Heijer den P, Linke A, Luha O, Ramondo A, Ussia G, Wenaweser P, Windecker S, Laborde JC, de Jaegere P, Serruys PW Procedural and 30-day outcomes following transcatheter aortic valve implantation using the third generation (18 Fr) corevalve revalving system: results from the multicentre, expanded evaluation registry 1-year following CE mark approval EuroIntervention 2008;4:242 –249 Rode´s-Cabau J, Webb JG, Cheung A, Ye J, Dumont E, Feindel CM, Osten M, Natarajan MK, Velianou JL, Martucci G, DeVarennes B, Chisholm R, Peterson MD, Lichtenstein SV, Nietlispach F, Doyle D, DeLarochellie`re R, Teoh K, Chu V, 2082b strategy for coronary artery revascularization before transcatheter aortic valve implantation Catheter Cardiovasc Interv 2013;81:376–383 54 Abdel-Wahab M, Mostafa AE, Geist V, Stoă cker B, Gordian K, Merten C, Richardt D, Toelg R, Richardt G Comparison of outcomes in patients having isolated transcatheter aortic valve implantation versus combined with preprocedural percutaneous coronary intervention Am J Cardiol 2012; 109:581 – 586 55 Wendt D, Kahlert P, Lenze T, Neuhaăuser M, Price V, Konorza T, Erbel R, Jakob H, Thielmann M Management of high-risk patients with aortic stenosis and coronary artery disease Ann Thorac Surg 2013;95:599 –605 56 Wenaweser P, Pilgrim T, Guerios E, Stortecky S, Huber C, Khattab AA, Kadner A, Buellesfeld L, Gloekler S, Meier B, Carrel T, Windecker S Impact of coronary artery disease and percutaneous coronary intervention on outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation EuroIntervention 2011;7:541 –548 J.M Paradis et al 57 Conradi L, Seiffert M, Franzen O, Baldus S, Schirmer J, Meinertz T, Reichenspurner H, Treede H First experience with transcatheter aortic valve implantation and concomitant percutaneous coronary intervention Clin Res Cardiol 2011;100:311–316 58 Geist V, Sherif MA, Khattab AA Successful percutaneous coronary intervention after implantation of a CoreValve percutaneous aortic valve Catheter Cardiovasc Interv 2009;73:61 –67 59 Zajarias A, Eltchaninoff H, Cribier A Successful coronary intervention after percutaneous aortic valve replacement Catheter Cardiovasc Interv 2007;69:522 –524 60 Pasic M, Dreysse S, Unbehaun A, Buz S, Drews T, Klein C, D’Ancona G Hetzer R Combined elective percutaneous coronary intervention andtransapical transcatheter aortic valve implantation Interact Cardiovasc Thorac Surg 2012;14:463–468 61 Goel SS, Ige M, Tuzcu EM, Ellis SG, Stewart WJ, Svensson LG, Lytle BW, Kapadia SR 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 Downloaded from http://eurheartj.oxfordjournals.org/ by guest on August 4, 2016 ... of both the epicardial coronary arteries and the aortic valve cusps as early as the second and third decades of life J.M Paradis et al Aortic stenosis and coronary artery disease Table Indications... time of aortic cross-clamping AS, aortic stenosis; TAVR, transcatheter aortic valve replacement; SAVR, surgical aortic valve replacement; CAD, coronary artery disease; CABG:, coronary artery bypass... 3, year mortality was 22, 44, and 56, respectively Aortic stenosis and coronary artery disease Table n/a PCI, percutaneous coronary intervention; SAVR, surgical aortic valve replacement; LVEF,