Listen to this manuscript’s

audio summary by

Editor-in-Chief

Dr. Valentin Fuster on

JACC.org.

J O U R N A L O F T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y V O L . 7 4 , N O . 3 , 2 0 1 9

ª 2 0 1 9 B Y T H E A M E R I C A N C O L L E G E O F C A R D I O L O G Y F O U N D A T I O N

P U B L I S H E D B Y E L S E V I E R

THE PRESENT AND FUTURE

JACC STATE-OF-THE-ART REVIEW

Coronary Artery Disease andTranscatheter Aortic Valve ReplacementJACC State-of-the-Art Review

Laurent Faroux, MD, MSC, Leonardo Guimaraes, MD, Jérôme Wintzer-Wehekind, MD, Lucia Junquera, MD,Alfredo Nunes Ferreira-Neto, MD, David del Val, MD, Guillem Muntané-Carol, MD, Siamak Mohammadi, MD,Jean-Michel Paradis, MD, Josep Rodés-Cabau, MD

ABSTRACT

ISS

Fro

fro

Va

ho

an

rep

Ma

About one-half of transcatheter aortic valve replacement (TAVR) candidates have coronary artery disease (CAD), and

controversial results have been reported regarding the effect of the presence and severity of CAD on clinical outcomes

post-TAVR. In addition to coronary angiography, promising data has been recently reported on both the use of computed

tomography angiography and the functional invasive assessment of coronary lesions in the work-up pre-TAVR. While

waiting for the results of ongoing randomized trials, percutaneous revascularization of significant coronary lesions has

been the routine strategy in TAVR candidates with CAD. Also, scarce data exists on the incidence, characteristics, and

management of coronary events post-TAVR, and increasing interest exist on potential coronary access challenges in

patients requiring coronary angiography/intervention post-TAVR. This review provides an updated overview of the

current landscape of CAD in TAVR recipients, focusing on its prevalence, clinical impact, pre- and post-procedural

evaluation and management, unresolved issues and future perspectives. (J Am Coll Cardiol 2019;74:362–72)

© 2019 by the American College of Cardiology Foundation.

T his review provides an updated overview ofthe current landscape of coronary artery dis-ease (CAD) in transcatheter aortic valve

replacement (TAVR) recipients, focusing on its preva-lence, clinical impact, pre- and post-proceduralevaluation and management, unresolved issues, andfuture perspectives.

EPIDEMIOLOGY

The prevalence of CAD has been w50% (1), and it hasdecreased from 81% to 15% in randomized controlledtrials along with the progressive reduction in meanage and surgical risk of enrolled patients (Figure 1)(2–9), with a much lower prevalence of CAD in

N 0735-1097/$36.00

m the Quebec Heart and Lung Institute, Laval University, Quebec City, Q

m Institut Servier; and has received research grants from Biotronik, Edw

l, and Muntané-Carol were supported by a grant from the Fundacion Alfon

lds the Research Chair “Fondation Famille Jacques Larivière” for the Dev

d has received institutional research grants from Edwards Lifesciences, Me

orted that they have no relationships relevant to the contents of this pap

nuscript received May 28, 2019; accepted June 10, 2019.

low-risk patients compared with intermediate- andhigh-risk patients. About one-half of TAVR candi-dates with CAD exhibit multivessel disease (10), anda mean Syntax score (SS) of w14 was recently re-ported in a series including 4,000 TAVR recipientswith CAD, with the involvement of the left main andleft anterior descending artery in 11% and 50% ofpatients, respectively (11).

CLINICAL IMPACT OF CAD IN

TAVR RECIPIENTS

Controversial results have been reported in manyobservational studies evaluating the clinicalimpact of CAD in patients undergoing TAVR

https://doi.org/10.1016/j.jacc.2019.06.012

uebec, Canada. Dr. Faroux was supported by a grant

ards Lifesciences, and Medtronic. Drs. Junquera, del

so Martin Escudero (Madrid, Spain). Dr. Rodés-Cabau

elopment of Structural Heart Disease Interventions;

dtronic, and Boston Scientific. All other authors have

er to disclose.

HIGHLIGHTS

� The impact of CAD in TAVR recipientsremains controversial, and no definitedata exist on the most appropriaterevascularization strategy in thesepatients.

� The use of CTA and hemodynamicassessment to guide pre-TAVRrevascularization will likely increase inthe coming years.

� The management of coronary eventsoccurring after TAVR (including coronaryaccess) requires further investigations.

AB BR E V I A T I O N S

AND ACRONYM S

AS = aortic stenosis

CA = coronary angiography

CABG = coronary artery bypass

graft

CAD = coronary artery disease

CTA = computed tomography

angiography

FFR = fractional flow reserve

iFR = instantaneous wave free

ratio

NSTEMI = non–ST-segment

elevation myocardial infarction

PCI = percutaneous coronary

intervention

rSS = residual Syntax score

SAVR = surgical aortic valve

replacement

SS = Syntax score

TAVR = transcatheter aortic

replacement

J A C C V O L . 7 4 , N O . 3 , 2 0 1 9 Faroux et al.J U L Y 2 3 , 2 0 1 9 : 3 6 2 – 7 2 CAD Management in TAVR Recipients

363

(Online Table 1). The results of these studies can begrouped into 3 categories: 1) studies showing anassociation between the presence of CAD (and itsseverity) and patient prognosis; 2) studies failing toshow such a relationship; and 3) studies showing noassociation between the presence of CAD and clin-ical outcomes, but a significant negative effect ofsevere CAD. Two recent meta-analyses showedcontradictory results regarding the association be-tween CAD and clinical outcomes post-TAVR (11,12).A significant heterogeneity between studies mayexplain such discordant results. First, the definitionof CAD was very variable, with only a minority ofstudies relying on an objective measurement ofcoronary lesion severity (quantitative coronaryangiography). Second, a hemodynamic assessmentwith fractional flow reserve (FFR) or instantaneouswave-free ratio (iFR) was rarely used to evaluatethe severity of CAD. Third, revascularizationcompleteness was generally left at the discretion ofoperator/heart team of each center, which may haveintroduced a significant bias and contributed to thedifferences between studies. Finally, the definitionof composite clinical endpoints was variable, andthe SS cut-off for defining CAD severity also variedacross studies. The presence of CAD and its severityare often associated with other comorbidities andhigh surgical risk scores, and the impact of CAD onthe prognosis frequently disappears after adjust-ment. Thus, it appears that the presence of CAD andits severity may be markers of comorbidity andincreased risk status rather than independent fac-tors of poorer outcomes. However, it has to benoted that most studies had a limited follow-up(usually <2 years), and longer time periods may beneeded to determine the real impact of CAD onclinical outcomes post-TAVR.

CAD ASSESSMENT

Coronary angiography (CA) remains thestandard examination for determining thepresence and severity of CAD in TAVR can-didates. However, recent studies evaluatedthe use of noninvasive coronary imagingtechniques, such as computed coronaryangiography (CTA), as well as coronary pres-sure wire measurements for determiningcoronary stenosis severity in the context ofTAVR, with promising preliminary data(13–25).COMPUTED TOMOGRAPHY ANGIOGRAPHY.

Some authors proposed to perform CA pre-TAVR only in a selected group of patientsaccording to the results of pre-proceduralelectrocardiogram-gated synchronized car-diac CTA findings. Chieffo et al. (13) showedthe feasibility and potential clinical relevanceof this strategy, with CA performed in only24% of TAVR candidates based on CTA results

(those cases with an obstructive coronary stenosisidentified on the CTA), and no negative clinicalimpact associated with the avoidance of CA on thebasis of CTA results.

Several studies have compared the performance ofcoronary CTA with CA for the detection of significantcoronary stenosis during the pre-TAVR work-up. Allstudies found an excellent CTA performance in termsof negative predictive value, at the cost of a relativelypoor specificity (Table 1) (14–20). Compared withcoronary CTA in patients without aortic stenosis (AS),similar sensitivity (95% vs. 99%) but a lower speci-ficity (65% vs. 88%) and a higher contrast volumehave been associated with coronary CTA during thepre-TAVR work-up (26,27). Evaluation of a previouslystented coronary segment was feasible in 69% to 92%of cases with a good diagnostic performance(14–16,18), whereas heavy calcifications generallyresulted in an increase of false positive results.Finally, it appears that using CTA as a gatekeeper forCA in the TAVR work-up could decrease the numberof coronary angiographies by 37% (26). This percent-age would likely increase in younger patients, with amuch lower probability of CAD and a lower degree ofcoronary artery calcification (28).

In summary, CTA has emerged as a reasonablealternative to CA for the evaluation of CAD pre-TAVR,and it may become an important tool in the stratifi-cation of CAD in TAVR candidates, particularly withthe increasing number of lower-risk patients. Twoongoing studies will provide further important

valve

TABLE 1

Detection

(Gold Sta

First Aut

Pontone e

Andreini e

Hamdan e

Harris et a

Opolski et

Matsumot

Rossi et a

CTA ¼ compredictive v

FIGURE 1 Coronary Artery Disease in Randomized Trials

100

80

60

40

20

PARTNER 1B (4

)

PARTNER 1A (6

)

PARTNER 2 (8)

PARTNER 3 (2)

SURTAVI (9)

Evolut L

ow Risk (3

)

CoreValv

e US Extr

eme R

isk (5

)

CoreValv

e US High Risk

(7)

0

Prev

alen

ce o

f CAD

(%)

Trends in CAD prevalence in randomized trials. CAD ¼ coronary artery dis-

ease; PARTNER ¼ Placement of Aortic Transcatheter Valves; SURTAVI ¼Surgical Replacement and Transcatheter Aortic Valve Implantation.

Faroux et al. J A C C V O L . 7 4 , N O . 3 , 2 0 1 9

CAD Management in TAVR Recipients J U L Y 2 3 , 2 0 1 9 : 3 6 2 – 7 2

364

information regarding the exact role of coronary CTAin this context (Table 2).

FFR AND iFR. In the presence of a coronary lesionwithout evidence of ischemia in the correspondingmyocardial territory, it is recommended that revas-cularization should be guided by hemodynamicfunctional assessment (29,30). Considering thatnoninvasive ischemia testing is rarely availablebefore CA in the TAVR work-up, hemodynamicassessment of coronary lesions should ideally beperformed to guide coronary revascularization insuch cases. However, scarce data exist on the

Diagnostic Value of the Electrocardiogram-Gated CTA for theof Significant Stenosis (>50%) Versus Coronary Angiography

ndard)

hor, Year (Ref. #) Sensitivity (%) Specificity (%) NPV (%) PPV (%)

t al., 2011 (14) 89 88 91 85

t al., 2014 (15) 90 91 95 81

t al., 2015 (16) 96 73 96 72

l., 2015 (17) 99 58 94 87

al., 2015 (18) 98 37 94 67

o et al., 2017 (19) 92 58 91 60

l., 2017 (20) 91 55 90 59

puted tomography angiography; NPV ¼ negative predictive value; PPV ¼ positivealue.

functional evaluation of coronary lesions in TAVRcandidates (Table 3).

Stanojevic et al. (31) demonstrated the safety andgood tolerance of intravenous adenosine in thispopulation, and several studies have used boluses ofintracoronary adenosine without any signal of poortolerance or side effects (21–25) (Table 3). However,left ventricular hypertrophy induced by AS may alterthe coronary flow reserve, potentially tampering thefinal results obtained by FFR. Ahmad et al. (21)showed that systemic and hyperemic coronary flowincreased significantly after TAVR (compared withthe values pre-TAVR). These results suggested thatFFR may underestimate coronary stenosis severity inpatients with severe AS, whereas coronary flow dur-ing the wave-free period of diastole did not changepost-TAVR, suggesting that iFR was not influenced bythe effect of the stenotic aortic valve. However,Pesarini et al. (22) showed that the mean FFR prior toTAVR did not significantly differ from the mean FFRimmediately after the TAVR. Yet, the mean FFRdecreased after TAVR in the subgroup of pathologicalFFR, whereas the average FFR increased in thenormal FFR subgroup. Of note, this variation in FFRchanged the therapeutic strategy (according to the0.80 threshold) in a minority (6%) of patients.

The iFR may be of interest in this population,because it does not require the administration of avasodilator. However, the common threshold of 0.89(32) for determining lesion severity may not be validin this population. In fact, it was shown that, in apopulation of patients with severe AS, a thresholdvalue of 0.93 excluded negative FFR (>0.80) with anegative predictive value of 98.4%, and a threshold of0.83 identified positive FFR (#0.80) with a positivepredictive value of 91.3%. Using a hybrid strategywith FFR only when iFR values were between 0.83and 0.93, the authors suggested that 63% of patientscan be assessed without adenosine while maintaining97% overall agreement with FFR lesion severityclassification (23). However, the same authors re-ported significant and mostly erratic individual vari-ations in iFR pre- and post-TAVR and concluded thatcaution is still advisable in the interpretation of iFR inthe presence of AS (24). Finally, Yamanaka et al. (25)showed, in a population of 95 patients with severeAS and intermediate coronary lesions previouslyassessed by myocardial perfusion scintigraphy, thatthere was a good correlation between FFR and iFR, aswell as between iFR and the presence of ischemia onscintigraphy (area under the curve of 0.89 and 0.84,respectively), using a cut-off of 0.82 for indicating apositive FFR and the presence of myocardial ischemiaon scintigraphy findings. Currently available

TABLE 2 Summary of Ongoing and Future Studies on CAD Evaluation and Management in TAVR Recipients

Study Study Design Population Sample Size Intervention Primary Endpoint

CT-CA(NCT03291925)

Randomized open-labeltrial (pilot study)

Patients with symptomatic severeAS eligible for TAVR

200 Selective invasive angiographybased on CT/coronary CTAimaging vs. systematicinvasive angiography

Number of patients enrolled in thestudy of all those that are eligible

FORTUNA(NCT03665389)

Prospective open-labelregistry (exploratory)

Patients with moderate stenoticlesions (30%–<70%) or severestenotic lesions on CTA who arecandidates for PCI followingTAVR

25 Measurement of iFR before TAVR,FFRct before TAVR andFFR þ iFR after TAVR

FFRct before TAVR

TCW(NCT03424941)

Randomized open-labelnoninferiority trial

Patients age $70 yrs with severe ASfeasible for treatment by both TFor TSc approach TAVR as well asconventional SAVR, and $2 denovo coronary lesions $50%diameter stenosis on main arteryor side branch >2 mm or singleLAD lesion >20 mm length orinvolving a bifurcation, feasiblefor treatment with CABG as wellas PCI

328 FFR-guided PCI and TAVR vs.CABG and SAVR

Composite of all-cause mortality,myocardial infarction, disablingstroke, unscheduled clinically-driven target vesselrevascularization, valvereintervention, and lifethreatening or disabling bleedingat 1 yr

FAITAVI(NCT03360591)

Randomized open-labeltrial

Patients with severe AS with theindication of TAVR and at leastone coronary stenosis >50% atangiography

320 Physiologically-guided strategy(PCI of lesions with FFR #0.80)vs. angiographically guidedstrategy (PCI of all lesions>50% by visual estimationof major branches >2.5 mm)

Composite of all-cause death,myocardial infarction, stroke,major bleeding and target vesselrevascularization at 1 yr

ACTIVATION(ISRCTN75836930)

Randomized trial Patients with symptomatic severe ASaccepted for TAVR, and $1proximal stenosis of $70% in amajor epicardial artery deemedsuitable for PCI

310 Pre-TAVR PCI vs. no pre-TAVR PCI Mortality and rehospitalization at 1 yr

NOTION-3(NCT03058627)

Randomized open-labeltrial

Patients with severe aortic stenosisselected for TAVR and at leastone coronary stenosis withFFR #0.80 or diameter stenosis>90% in a coronaryartery $2.5 mm

452 TAVR only vs. TAVR þ FFR-guidedcomplete revascularization

All-cause mortality, myocardialinfarction, or urgentrevascularization at 1 yr

ACTIVATION ¼ Assessing the effects of stenting in significant coronary artery disease prior to transcatheter aortic valve implantation; AS ¼ aortic stenosis; CABG ¼ coronary artery bypass graft;CT ¼ computed tomography; CTA ¼ computed tomography angiography; CT-CA ¼ Primary Non-invasive Cardiac Computed Tomography Versus Routine Invasive Angiography Prior to TAVI; FAITAVI ¼Functional Assessment in TAVI: FAITAVI; FFR¼ fractional flow reserve; FORTUNA¼ Evaluation of Fractional Flow Reserve Calculated by Computed Tomography Coronary Angiography in Patients UndergoingTAVR; iFR ¼ instantaneous wave-free ratio; LAD ¼ left anterior descending; NOTION-3 ¼ Revascularization in Patients Undergoing Transcatheter Aortic Valve Implantation; PCI ¼ percutaneous coronaryintervention; SAVR ¼ surgical aortic valve replacement; TAVR ¼ transcatheter aortic valve replacement; TCW ¼ The TransCatheter Valve and Vessels Trial; TF ¼ transfemoral; TSc ¼ trans-subclavian.

J A C C V O L . 7 4 , N O . 3 , 2 0 1 9 Faroux et al.J U L Y 2 3 , 2 0 1 9 : 3 6 2 – 7 2 CAD Management in TAVR Recipients

365

evidence suggests the use of FFR with the usual 0.80cut-off and a threshold of 0.89 or less for iFR for theevaluation of CAD severity in TAVR candidates.Nevertheless, these data remain preliminary, and thelevel of evidence is low. Future studies with a largernumber of patients and further validation with clin-ical events should determine the optimal FFR and iFRcut-off values to be used in TAVR candidates. Pre-liminary data showed a very low rate of coronaryevents at midterm follow-up among those patientswho had FFR and/or iFR evaluation pre-TAVR(22,23,31) (Table 3). However, long-term follow-updata will be needed to confirm the clinical validity ofthis strategy.

Overall, preliminary clinical data with the use ofFFR/iFR in TAVR candidates are promising, and thisfunctional evaluation of coronary lesions, alreadywell established in stable CAD patients without AS,should probably be implemented in the evaluation

of such patients. Two ongoing randomized clinicaltrials will further determine the role of invasivefunctional assessment of coronary lesions pre-TAVR(Table 2).

CORONARY

REVASCULARIZATION PRE-TAVR

The clinical relevance of percutaneous coronaryintervention (PCI) performed during the TAVR work-up remains to be determined. Indeed, randomizedtrials failed to demonstrate a clear beneficial effect ofPCI in stable CAD patients (33,34), and currentguidelines state that performing PCI in the presenceof a coronary artery stenosis >70% in proximal coro-nary segments during the pre-TAVR work-up lacksscientific evidence (35,36).

Numerous observational studies have shown thelack of differences in clinical outcomes in patients

TABLE 3 Summary of Studies Evaluating the Use of FFR During the Pre-TAVR Work-Up

First Author, Year(Ref. #) Population FFR Measurement Protocol Related Side Effects Treated Lesions Follow-Up

Stanojevic et al.,2016 (31)

82 lesions(n ¼ 72)

Peripheral intravenous infusion of140 mg/kg/min adenosine for upto 4 min (infusion terminated earlierthan this time frame if a value <0.80was attained, or if hemodynamicalterations resulting in adversesymptoms were noted)

1 AV blockNo symptomatic hypotension resulting in

cessation of adenosine infusion

PCI performed for37 of 82lesions

At a median follow up of19 � 14 months afterTAVR:

4 ACS, no TVR or TLR

Pesarini et al.,2016 (22)

133 lesions(n ¼ 54)

Intracoronary bolus of 150 to 250 mgadenosine without nitroglycerinadministration

None PCI performed for19 of 133lesions(n ¼ 17)

At 30 days:No sustained angina or

hypotension,myocardialinfarction, or heartfailure

Scarsini et al.,2018 (23)

141 lesions(n ¼ 62)

Intracoronary bolus of 150 to 250 mgadenosine without nitroglycerinadministration

None PCI performed for19 of 141lesions(n ¼ 17)

At 30 days:No death or new

coronaryrevascularization

Ahmad et al.,2018 (21)

30 lesions(n ¼ 28)

Intracoronary bolus of 150 mg adenosine None Missinginformation

Missing information

Yamanaka et al.,2018 (25)

116 vessels(n ¼ 95)

Intravenous infusion of adenosine at a doseof 140 mg/kg/min via a central or largeantecubital vein

Systolic blood pressure fluctuations ofmore than 40 mm Hg in 12 of 116 vessels

Maximal systolic blood pressure fluctuationof 90 mm Hg in 1 of 116 vessels

1 intermittent AV blockNo ventricular arrhythmias, bronchospasm,

thrombus formation or coronarydissection

Missinginformation

Missing information

ACS ¼ acute coronary syndrome; AV ¼ atrioventricular; TLR ¼ target lesion revascularization; TVR ¼ target vessel revascularization; other abbreviations as in Table 2.

Faroux et al. J A C C V O L . 7 4 , N O . 3 , 2 0 1 9

CAD Management in TAVR Recipients J U L Y 2 3 , 2 0 1 9 : 3 6 2 – 7 2

366

undergoing TAVR þ PCI versus isolated TAVR (OnlineTable 2), and a recent meta-analysis showed that PCIpre-TAVR was not associated with any increase in1-year mortality (10). These results have generallybeen interpreted as a proof of the feasibility andsafety of PCI in this context. Also, several studieshave examined the completeness of coronary revas-cularization in TAVR candidates with CAD, most oftenusing the residual Syntax score (rSS) (Online Table 3).Interestingly, many studies have shown the negativeimpact of incomplete coronary revascularizationand/or high rSS, and this negative impact remainedsignificant after adjustment for potential con-founders. These results are further supported by 2recent meta-analyses confirming that patients withhigh rSS have a higher mortality after TAVR (11,37).However, the selection of which coronary lesions totreat and the completeness of revascularization wasusually left to the discretion of the operator/heartteam of each center and may have been influenced byother factors (e.g., angina or decreased left ventricu-lar ejection fraction), leading to a large variability onPCI strategies across studies that may indeed havehad an impact on clinical outcomes.

Randomized trials comparing TAVR and surgicalaortic valve replacement (SAVR) for the treatment oflow- to intermediate-risk patients with severe symp-tomatic AS have included patients with CAD (2,3,8,9).

All CAD patients included in these trials were eligiblefor either PCI or coronary artery bypass graft (CABG),and those allocated to TAVR received PCI within theweeks prior to the procedure, whereas those allocatedto SAVR underwent concomitant CABG. About 12%(range 4% to 22%) of patients included had coronaryrevascularization (either by PCI or CABG) in additionto TAVR or SAVR (2,3,8,9) (Figure 2). The global re-sults of all randomized trials showed either the non-inferiority or superiority of TAVR versus SAVR for thecombined endpoint of mortality or stroke at midtermfollow-up (1 to 2 years). Although patients with CADrequiring revascularization represented a minority,these results indirectly supported the strategy ofTAVR þ PCI versus SAVR þ CABG in the treatment ofAS and CAD. Unfortunately, specific data on patientsreceiving coronary revascularization (PCI or CABG)was provided only in the recently publishedPARTNER 3 (The Safety and Effectiveness of theSAPIEN 3 Transcatheter Heart Valve in Low Risk Pa-tients With Aortic Stenosis) trial, showing the lack ofdifferences between TAVR þ PCI (n ¼ 32) and SAVR þCABG (n ¼ 58). Thus, the rate of the combinedendpoint of mortality/stroke/rehospitalization was9.4% in the TAVR þ PCI group versus 12.1% in theSAVR þ CABG group (hazard ratio: 0.77; 95% confi-dence interval: 0.20 to 2.98) (2). However, it shouldbe noted that no data on periprocedural (PCI)

FIGURE 2 Coronary Revascularization in Randomized Trials

PARTNER 2 (8)

PARTNER 3 (2)

Evolut L

ow Risk (3

)

SURTAVI (9)

25%

20%

15%

10%

5%

0%

TAVR + PCI SAVR + CABG

Percentage of patients who underwent TAVR þ PCI and SAVR þ CABG in

randomized trials. CABG ¼ coronary artery bypass graft;

PCI ¼ percutaneous coronary intervention; SAVR ¼ surgical aortic valve

replacement; TAVR ¼ transcatheter aortic valve replacement.

J A C C V O L . 7 4 , N O . 3 , 2 0 1 9 Faroux et al.J U L Y 2 3 , 2 0 1 9 : 3 6 2 – 7 2 CAD Management in TAVR Recipients

367

myocardial infarction were available. In addition,patients with complex CAD (including left main cor-onary artery or with an SS >22 or 32) were excludedfrom randomized trials. Chakravarty et al. (38)recently provided reassuring data on the safety ofleft main PCI in TAVR candidates, and some teamshave reported the feasibility of using mechanicalsupport (such as Impella, Abiomed, Danvers, Massa-chusetts; or TandemHeart, TandemLife, Pittsburgh,Pennsylvania) (39,40) or performing balloon aorticvalvuloplasty (41) prior to complex PCI in patientswith severe AS. Future studies are needed to deter-mine the clinical outcomes in patients with complexCAD undergoing PCI þ TAVR.

Two ongoing randomized trials are trying todetermine the usefulness of coronary revasculariza-tion with PCI (vs. no revascularization) in patientswith CAD undergoing TAVR (Table 2).

Although ticagrelor is considered a potential choicefor high-risk PCI in stable patients (29), no data existon the potential risk of increased bleeding events inthe periprocedural TAVR period in patients underticagrelor treatment. While waiting for additionaldata, we consider that the combination of aspirin þclopidogrel should be prioritized in these patients,with a dual antiplatelet therapy duration that shouldbe individualized between 1 and 6 months (29,42).

TIMING OF CORONARY

REVASCULARIZATION PRE-TAVR

When a PCI indication is established, it is usuallyperformed upstream of TAVR. However, a staged PCIprior to TAVR is inevitably associated with an addi-tional vascular puncture, repeated injection ofcontrast media, and dual antiplatelet therapy, whichmay increase the complication rates following TAVR.Thus, the optimal timing of PCI prior to TAVR remainsunclear.

van Rosendael et al. (43) compared the clinicaloutcomes of patients undergoing PCI within 30 daysor >30 days before TAVR and failed to show signifi-cant differences between groups in overall mortalityafter a median follow-up of 2 years. However, a sig-nificant increase in minor vascular injury andbleeding complications after TAVR was observed inthe group who had PCI performed within 30 daysbefore TAVR. Singh et al. (44) showed that patientswho underwent PCI during the same hospitalizationas the TAVR procedure had a higher in-hospitalmortality. Finally, several studies have shown thefeasibility and safety of TAVR and concomitant PCI(45–50). Although this strategy has the advantage ofavoiding multiple procedures and can potentially

reduce the risks associated with obtaining vascularaccess at different time points, it increases theamount of contrast media administered at the time ofthe TAVR procedure and could potentially increasethe risk of contrast nephropathy, particularly in pa-tients with complex CAD.

In summary, no definite data exist on the timing ofPCI in TAVR candidates with significant CAD. Whilestaging the PCI and TAVR procedures remains themost common strategy, controversial data exist onthe most appropriate (minimum) delay between PCIand TAVR. In the absence of further data, no specifictiming strategy can be recommended in this setting.However, the presence of both complex CAD and risksfactors for contrast nephropathy (e.g., history ofchronic kidney injury) should probably be consideredwhen establishing a minimum delay betweenprocedures.

CORONARY EVENTS AFTER TAVR

EPIDEMIOLOGY AND PATHOPHYSIOLOGY. AS andCAD share some common risk factors, and somestudies have suggested a similar pathophysiologicalprocess for both entities (51). However, little data isavailable on the incidence of coronary events after

FIGURE 3 Examples of Coronary Events Post-TAVR

Case 1: (A) Pre-TAVR coronary angiogram. (B) De novo stenosis at the distal left circumflex artery revealed by a NSTEMI (8 months after TAVR). (C) PCI result. Case 2:

Pre-TAVR coronary angiogram before (D) and after (E) PCI. In-stent restenosis at the proximal left circumflex artery revealed by a NSTEMI (9 months after TAVR)

before (F) and after (G) PCI. Case 3: (H) Coronary angiogram showing a thrombus located on the crux cordis revealed by a NSTEMI (13 months after TAVR). (I) Computed

tomography angiography showing an external partial thrombosis of the TAVR bioprosthesis. NSTEMI ¼ non–ST-segment elevation myocardial infarction; other

abbreviations as in Table 2.

Faroux et al. J A C C V O L . 7 4 , N O . 3 , 2 0 1 9

CAD Management in TAVR Recipients J U L Y 2 3 , 2 0 1 9 : 3 6 2 – 7 2

368

TAVR. Vilalta et al. (52) reported, in a cohort of 779TAVR recipients, an incidence of acute coronarysyndrome (ACS) of 10% after a median follow-up ofabout 2 years after TAVR. Up to 36% of the ACS eventsconsisted of non–ST-segment elevation myocardialinfarction (NSTEMI) type 2, followed by unstableangina (35%), NSTEMI type 1 (28%), and STEMI (1%).Finally, only 39% of the patients benefited from PCI.Of note, the prognosis of ACS occurring after TAVRwas poor, with an all-cause mortality of 37% after amedian follow-up of 21 months post-ACS.

The majority of coronary events occurring afterTAVR are likely related to an atherothromboticmechanism, either by the progression of CAD, or thefailure of a PCI performed before the TAVR (Figure 3).Moreover, some authors have hypothesized otherpotential mechanisms, such as impaired coronaryflow dynamics and coronary hypoperfusion related tothe TAVI bioprosthesis (53), a coronary embolismrelated to subclinical leaflet thrombosis in bio-prosthetic aortic valves thrombosis (54) (Figure 3), alate valve migration occluding a coronary ostia

TABLE 4 Summary of Studies on the Feasibility of PCI After TAVR

First Author,Year (Ref. #) Population Devices and Results Conclusions

Blumenstein et al.,2015 (58)

35 patients who underwent CA or PCIafter TAVR

Sapien XT: 19 of 19 selective CA; 8 of 8successful PCI

CoreValve: 3 of 10 selective CA, 6 of 10nonselective CA, 1 of 10 nondiagnostic CA;no PCI

Symetis: 2 of 4 selective CA, 2 of 4nonselective CA; 1 of 1 successful PCI

Jena: 1 of 1 selective CA; no PCIPortico: 1 of 1 nonselective CA; 1 of 1

successful PCI

Selective CA and PCI in patients with prior TAVR is generallyfeasible.

Depending on stent frame type, the procedure can bechallenging or even unfeasible.

Allali et al.,2016 (59)

24 PCI procedures in 17 patients withCoreValve bioprosthesis

4 of 24: difficult ostium intubation andsuboptimal stability

23 of 24 procedural success (1 proceduraldeath)

PCI after implantation of the self-expanding CoreValve is mostlyfeasible and safe.

Selective intubation of the native coronary may be challenging.

Chakravarty et al.,2016 (38)

9 LM PCI: 4 patients with CoreValveand 5 with Edwards

9 of 9 successful PCI LM PCI was feasible with self-expandable and balloonexpandable TAVR bioprosthesis.

Chetcuti et al.,2016 (60)

190 CA and 113 attempted PCI in 169patients with CoreValve bioprosthesis

186 of 190 successful CA103 of 113 successful PCI

CA and PCI are possible in nearly all patients with CoreValvebioprosthesis.

Zivelonghi et al.,2016 (61)

66 patients who underwent CA orPCI after TAVR

Evolut R: 24 of 25 successful CA (of which 4semiselective) and 6 of 6 successful PCI

Sapien 3: 41 of 41 successful CA (of which 2semiselective) and 13 of 13 successful PCI

Catheterization of the coronary ostia after TAVR with balloon orself-expandable valves is safe and feasible in almost allcases.

Boukantar et al.,2017 (62)

16 patients with CoreValve 9 of 16 adequate coronary opacification6 of 7 successful PCI

CA after CoreValve TAVR are feasible but challenging.

Htun et al.,2017 (63)

43 CA in 28 patients with CoreValve orEvolut R

42 of 43 selective LMCA engagement29 of 32 selective RCA engagement29 of 29 successful PCI

CA and PCI after TAVR are feasible and safe with supra-annularself-expandable valve.

Tanaka et al.,2019 (64)

40 patients with CoreValve or Evolut R 16 of 32 RCA angiography success28 of 32 LCA angiography success28 of 30 PCI success

CA and PCI following CoreValve TAVR is safe and feasible inmost cases.

Success rate of selective RCA angiography is relatively low.

CA ¼ coronary angiogram; LCA ¼ left coronary artery; LM ¼ left main stem; RCA ¼ right coronary artery; other abbreviations as in Table 2.

J A C C V O L . 7 4 , N O . 3 , 2 0 1 9 Faroux et al.J U L Y 2 3 , 2 0 1 9 : 3 6 2 – 7 2 CAD Management in TAVR Recipients

369

initially partially covered but not occluded (55,56),and a hypersensitivity reaction against metal anionspresent into the device (Kounis syndrome) (57).Future studies are needed to better categorize thetype and frequency of coronary events post-TAVR,and further investigate the factors determining theoccurrence and poor outcomes of patients experi-encing such events.

CORONARY ACCESS AFTER TAVR. Irrespective ofthe mechanisms leading to a coronary event post-TAVR, obtaining appropriate images of the coronaryarteries by selective CA is frequently mandatory forestablishing an appropriate diagnosis and therapeuticstrategy. The presence of a TAVR bioprosthesis couldpotentially make the selective catheterization ofcoronary ostia difficult or even impossible. Althoughit seems obvious that the type of transcatheter valve(and its geometry) may have an effect on coronaryaccess, no studies have yet shown differences incoronary access and CA and PCI feasibility accordingto transcatheter valve type. Available data are relatedto isolated cases and small series globally, including190 reports of CA and/or PCI in patients with a TAVRbioprosthesis (Table 4), with rates of successful se-lective CA ranging from 50% to 100% (38,58–64).

Yudi et al. (65) recently proposed a catheter se-lection algorithm depending on the type of bio-prosthesis (CoreValve, Medtronic, Minneapolis,Minnesota; or Sapien, Edwards, Irvine, California),the type of procedure (CA or PCI), and the position ofthe transcatheter valve commissure with respect tothe coronary ostium. Also, the authors recommendedthe systematic use of 6-F catheters, as well asselecting a femoral or left radial approach for patientswith a Medtronic CoreValve system, and a femoral orradial (left or right) approach for patients with anEdwards Sapien valve. Data from our experience(unpublished) including 41 patients with a SAPIEN orSAPIEN XT valve undergoing repeat CA or PCI showedno increased difficulties (number of catheters used,procedural time, contrast volume) with respect topre-procedural CA/PCI. In about two-thirds of thecases, the procedure was performed with no need forcrossing through the struts of the stent valve frame(coronary ostia were frequently located at the level orabove the top of the stent frame). Thus, we considerthat no particular changes in catheters (size or type)or approach (right radial) would be required in suchcases. On the other hand, although not definitelyproven, there is increased concern regarding coronary

CENTRAL ILLUSTRATION Coronary Artery Disease Management Before and After Transcatheter AorticValve Replacement

Faroux, L. et al. J Am Coll Cardiol. 2019;74(3):362–72.

Current evidence and future perspectives of CAD management before and after TAVR. ACS ¼ acute coronary syndrome; CAD ¼ coronary artery disease;

CTA ¼ computed tomography angiography; FFR¼ fractional flow reserve; iFR¼ instantaneous wave-free ratio; PCI¼ percutaneous coronary intervention; RCA ¼ right

coronary artery; TAVR ¼ transcatheter aortic valve replacement.

Faroux et al. J A C C V O L . 7 4 , N O . 3 , 2 0 1 9

CAD Management in TAVR Recipients J U L Y 2 3 , 2 0 1 9 : 3 6 2 – 7 2

370

access in the presence of some self-expanding valvesdue to the taller valve frame and supra-annular valve.In particular, catheterization of the right coronaryartery can be particularly challenging in these cases,and we agree with the main recommendations fromYudi et al. (65) in this context. Also, the use of theBarbeau curve catheter (with a slightly larger sec-ondary curve with respect to the Judkins right cath-eter) may be helpful in some cases. Future studieswill need to validate these recommendations andfurther determine the feasibility and failure ratesregarding selective CA/PCI for each transcathetervalve type.

CONCLUSIONS AND FUTURE PERSPECTIVES

CAD remains one of the most frequent comorbid-ities among TAVR candidates (Central Illustration).While controversial results have been reported

regarding its clinical impact, revascularization (PCI)pre-TAVR of lesions located in the proximal-midcoronary segments remains the most commonpractice worldwide. Ongoing randomized trialsshould determine the efficacy of this strategy (vs.no revascularization) in the coming years. Also, themost appropriate timing of PCI pre-TAVR remainsundetermined, and the possibility of a combinedprocedure (PCI at the time of TAVR) merits furtherevaluation, particularly in patients with no complexCAD or kidney dysfunction. The use of noninvasivemethods like coronary CTA in the pre-TAVR work-up, and a more accurate evaluation of coronarylesion severity with coronary pressure wire mea-surements have shown to be associated with goodpreliminary results and will likely increase in thecoming years; several ongoing studies are going toclarify the exact role of these technologies in theTAVR field. Finally, scarce data exist on the

J A C C V O L . 7 4 , N O . 3 , 2 0 1 9 Faroux et al.J U L Y 2 3 , 2 0 1 9 : 3 6 2 – 7 2 CAD Management in TAVR Recipients

371

occurrence, impact, and management of coronaryevents post-TAVR. Apart from better understandingthe pathophysiology and establishing the mostappropriate treatment strategy in such cases, moredata is urgently needed regarding the coronary ac-cess (feasibility and failure rate) across differenttranscatheter valve types (Central Illustration). Thefact that many patients with a coronary syndromepost-TAVR are treated in centers with no TAVRexperience further highlights the importance ofestablishing clear recommendations regarding se-lective CA and PCI in these cases. The recent pub-lication of 2 randomized trials with positive results

for TAVR in a low-risk AS population has provideddefinite evidence for extending this treatment to-ward younger and lower-risk patients. However, abetter understanding of the diagnosis, prognosis,and management of CAD pre- and post-procedurewill be needed in the process of the final expan-sion of TAVR.

ADDRESS FOR CORRESPONDENCE: Dr. JosepRodés-Cabau, Quebec Heart & Lung Institute, LavalUniversity, 2725 Chemin Ste-Foy, Quebec City,Quebec G1V4G5, Canada. E-mail: josep.rodes@criucpq.ulaval.ca. Twitter: @IUCPQ.

RE F E RENCE S

1. Walther T, Hamm CW, Schuler G, et al. Periop-erative results and complications in 15,964 trans-catheter aortic valve replacements: prospectivedata from the GARY Registry. J Am Coll Cardiol2015;65:2173–80.

2. Mack MJ, Leon MB, Thourani VH, et al. Trans-catheter aortic-valve replacement with a balloon-expandable valve in low-risk patients. N Engl JMed 2019;380:1695–705.

3. Popma JJ, Deeb GM, Yakubov SJ, et al. Trans-catheter aortic-valve replacement with a self-expanding valve in low-risk patients. N Engl JMed 2019;380:1706–15.

4. Leon MB, Smith CR, Mack M, et al. Trans-catheter aortic-valve implantation for aortic ste-nosis in patients who cannot undergo surgery.N Engl J Med 2010;363:1597–607.

5. Popma JJ, Adams DH, Reardon MJ, et al.Transcatheter aortic valve replacement using aself-expanding bioprosthesis in patients with se-vere aortic stenosis at extreme risk for surgery.J Am Coll Cardiol 2014;63:1972–81.

6. Smith CR, Leon MB, Mack MJ, et al. Trans-catheter versus surgical aortic valve replacementin high-risk patients. N Engl J Med 2011;364:2187–98.

7. Adams DH, Popma JJ, Reardon MJ, et al.Transcatheter aortic-valve replacement with aself-expanding prosthesis. N Engl J Med 2014;370:1790–8.

8. Leon MB, Smith CR, Mack MJ, et al. Trans-catheter or surgical aortic-valve replacement inintermediate-risk patients. N Engl J Med 2016;374:1609–20.

9. Reardon MJ, Van Mieghem NM, Popma JJ, et al.Surgical or transcatheter aortic-valve replacementin intermediate-risk patients. N Engl J Med 2017;376:1321–31.

10. Kotronias RA, Kwok CS, George S, et al.Transcatheter aortic valve implantation with orwithout percutaneous coronary artery revascular-ization strategy: a systematic review and meta-analysis. J Am Heart Assoc 2017;6:e005960.

11. D’Ascenzo F, Verardi R, Visconti M, et al. In-dependent impact of extent of coronary arterydisease and percutaneous revascularisation on

30-day and one-year mortality after TAVI: a meta-analysis of adjusted observational results. Euro-Intervention 2018;14:e1169–77.

12. Sankaramangalam K, Banerjee K,Kandregula K, et al. Impact of coronary arterydisease on 30-day and 1-year mortality in patientsundergoing transcatheter aortic valve replace-ment: a meta-analysis. J Am Heart Assoc 2017;6:e006092.

13. Chieffo A, Giustino G, Spagnolo P, et al.Routine screening of coronary artery disease withcomputed tomographic coronary angiography inplace of invasive coronary angiography in patientsundergoing transcatheter aortic valve replace-ment. Circ Cardiovasc Interv 2015;8:e002025.

14. Pontone G, Andreini D, Bartorelli AL, et al.Feasibility and accuracy of a comprehensive mul-tidetector computed tomography acquisition forpatients referred for balloon-expandable trans-catheter aortic valve implantation. Am Heart J2011;161:1106–13.

15. Andreini D, Pontone G, Mushtaq S, et al.Diagnostic accuracy of multidetector computedtomography coronary angiography in 325 consec-utive patients referred for transcatheter aorticvalve replacement. Am Heart J 2014;168:332–9.

16. Hamdan A, Wellnhofer E, Konen E, et al. Cor-onary CT angiography for the detection of coro-nary artery stenosis in patients referred fortranscatheter aortic valve replacement.J Cardiovasc Comput Tomogr 2015;9:31–41.

17. Harris BS, De Cecco CN, Schoepf UJ, et al.Dual-source CT imaging to plan transcatheteraortic valve replacement: accuracy for diagnosis ofobstructive coronary artery disease. Radiology2015;275:80–8.

18. Opolski MP, Kim WK, Liebetrau C, et al. Diag-nostic accuracy of computed tomography angi-ography for the detection of coronary arterydisease in patients referred for transcatheteraortic valve implantation. Clin Res Cardiol 2015;104:471–80.

19. Matsumoto S, Yamada Y, Hashimoto M, et al.CT imaging before transcatheter aortic valve im-plantation (TAVI) using variable helical pitchscanning and its diagnostic performance for cor-onary artery disease. Eur Radiol 2017;27:1963–70.

20. Rossi A, De Cecco CN, Kennon SRO, et al. CTangiography to evaluate coronary artery diseaseand revascularization requirement before trans-catheter aortic valve replacement. J CardiovascComput Tomogr 2017;11:338–46.

21. Ahmad Y, Götberg M, Cook C, et al. Coronaryhemodynamics in patients with severe aortic ste-nosis and coronary artery disease undergoingtranscatheter aortic valve replacement: implica-tions for clinical indices of coronary stenosisseverity. J Am Coll Cardiol Cardiovasc Interv 2018;11:2019–31.

22. Pesarini G, Scarsini R, Zivelonghi C, et al.Functional assessment of coronary artery diseasein patients undergoing transcatheter aortic valveimplantation: influence of pressure overload onthe evaluation of lesions severity. Circ CardiovascInterv 2016;9:e004088.

23. Scarsini R, Pesarini G, Lunardi M, et al. Ob-servations from a real-time, iFR-FFR “hybridapproach” in patients with severe aortic stenosisand coronary artery disease undergoing TAVI.Cardiovasc Revasc Med 2018;19:355–9.

24. Scarsini R, Pesarini G, Zivelonghi C, et al.Physiologic evaluation of coronary lesions usinginstantaneous wave-free ratio (iFR) in patientswith severe aortic stenosis undergoing trans-catheter aortic valve implantation. Euro-Intervention 2018;13:1512–9.

25. Yamanaka F, Shishido K, Ochiai T, et al.Instantaneous wave-free ration for the assessmentof intermediate coronary artery stenosis in pa-tients with severe aortic valve stenosis: compari-son with myocardial perfusion scintigraphy. J AmColl Cardiol Cardiovasc Interv 2018;11:2032–40.

26. van den Boogert TPW, Vendrik J,Claessen BEPM, et al. CTCA for detection of sig-nificant coronary artery disease in routine TAVIwork-up: a systematic review and meta-analysis.Neth Heart J 2018;26:591–9.

27. Yang L, Zhou T, Zhang R, et al. Meta-analysis:diagnostic accuracy of coronary CT angiographywith prospective ECG gating based on step-and-shoot, flash and volume modes for detection ofcoronary artery disease. Eur Radiol 2014;24:2345–52.

Faroux et al. J A C C V O L . 7 4 , N O . 3 , 2 0 1 9

CAD Management in TAVR Recipients J U L Y 2 3 , 2 0 1 9 : 3 6 2 – 7 2

372

28. Raff GL, Gallagher MJ, O’Neill WW,Goldstein JA. Diagnostic accuracy of noninvasivecoronary angiography using 64-slice spiralcomputed tomography. J Am Coll Cardiol 2005;46:552–7.

29. Neumann FJ, Sousa-Uva M, Ahlsson A, et al.2018 ESC/EACTS guidelines on myocardial revas-cularization. Eur Heart J 2019;40:87–165.

30. Fihn SD, Blankenship JC, Alexander KP, et al.2014 ACC/AHA/AATS/PCNA/SCAI/STS focusedupdate of the guideline for the diagnosis andmanagement of patients with stable ischemicheart disease. J Am Coll Cardiol 2014;64:1929–49.

31. Stanojevic D, Gunasekaran P, Tadros P, et al.Intravenous adenosine infusion is safe and welltolerated during coronary fractional flow reserveassessment in elderly patients with severe aorticstenosis. J Invasive Cardiol 2016;28:357–61.

32. Götberg M, Cook CM, Sen S, Nijjer S,Escaned J, Davies JE. The evolving future ofinstantaneous wave-free ratio and fractional flowreserve. J Am Coll Cardiol 2017;70:1379–402.

33. Boden WE, O’Rourke RA, Teo KK, et al. Optimalmedical therapy with or without PCI for stablecoronary disease. N Engl J Med 2007;356:1503–16.

34. Al-Lamee R, Thompson D, Dehbi HM, et al.Percutaneous coronary intervention in stableangina (ORBITA): a double-blind, randomisedcontrolled trial. Lancet 2018;391:31–40.

35. Nishimura RA, Otto CM, Bonow RO, et al. 2014AHA/ACC guideline for the management of pa-tients with valvular heart disease: executive sum-mary. J Am Coll Cardiol 2014;63:2438–88.

36. Baumgartner H, Falk V, Bax JJ, et al. 2017 ESC/EACTS guidelines for the management of valvularheart disease. Eur Heart J 2017;38:2739–91.

37. Witberg G, Zusman O, Codner P, Assali A,Kornowski R. Impact of coronary artery revascu-larization completeness on outcomes of patientswith coronary artery disease undergoing trans-catheter aortic valve replacement: a meta-analysisof studies using the residual SYNTAX Score (Syn-ergy Between PCI With Taxus and Cardiac Sur-gery). Circ Cardiovasc Interv 2018;11:e006000.

38. Chakravarty T, Sharma R, Abramowitz Y, et al.Outcomes in patients with transcatheter aorticvalve replacement and left main stenting: theTAVR-LM registry. J Am Coll Cardiol 2016;67:951–60.

39. Spiro J, Venugopal V, Raja Y, Ludman PF,Townend JN, Doshi SN. Feasibility and efficacy ofthe 2.5 L and 3.8 L Impella percutaneous leftventricular support device during high-risk,percutaneous coronary intervention in patientswith severe aortic stenosis. Catheter CardiovascInterv 2015;85:981–9.

40. Alkhouli M, Al Mustaga A, Chaker Z,Alqahtani F, Aljohani S, Holmes DR. Mechanicalcirculatory support in patients with severe aorticstenosis and left ventricular dysfunction under-going percutaneous coronary intervention. J CardSurg 2017;32:245–9.

41. Daniec M, Sorysz D, Dzierwierz, et al. In-hos-pital and long-term outcomes of percutaneousballoon aortic valvuloplasty with concomitant

percutaneous coronary intervention in patientswith severe aortic stenosis. J Interv Cardiol 2018;31:60–7.

42. Levine GN, Bates ER, Bittl JA, et al. 2016 ACC/AHA guideline focused update on duration of dualantiplatelet therapy in patients with coronary ar-tery disease: a report of the American College ofCardiology/American Heart Association Task Forceon Clinical Practice Guidelines. J Am Coll Cardiol2016;68:1082–115.

43. van Rosendael PJ, van der Kley F,Kamperidis V, et al. Timing of staged percutaneouscoronary intervention before transcatheter aorticvalve implantation. Am J Cardiol 2015;115:1726–32.

44. Singh V, Rodriguez AP, Thakkar B, et al.Comparison of outcomes of transcatheter aorticvalve replacement plus percutaneous coronaryintervention versus transcatheter aortic valvereplacement alone in the United States. Am JCardiol 2016;118:1698–704.

45. Wenaweser P, Pilgrim T, Guerios E, et al.Impact of coronary artery disease and percuta-neous coronary intervention on outcomes in pa-tients with severe aortic stenosis undergoingtranscatheter aortic valve implantation. Euro-Intervention 2011;7:541–8.

46. Conradi L, Seiffert M, Franzen O, et al. Firstexperience with transcatheter aortic valve im-plantation and concomitant percutaneous coro-nary intervention. Clin Res Cardiol 2011;11:311–6.

47. Pasic M, Dreysse S, Unbehaun A, et al. Com-bined elective percutaneous coronary interventionand transapical transcatheter aortic valve implan-tation. Interact Cardiovasc Thorac Surg 2012;14:463–8.

48. Griese DP, Reents W, Tóth A, Kerber S,Diegeler A, Babin-Ebell J. Concomitant coronaryintervention is associated with poorer early andlate clinical outcomes in selected elderly patientsreceiving transcatheter aortic valve implantation.Eur J Cardiothorac Surg 2014;46:e1–7.

49. Penkalla A, Pasic M, Drews T, et al. Trans-catheter aortic valve implantation combined withelective coronary artery stenting: a simultaneousapproach. Eur J Cardiothorac Surg 2015;47:1083–9.

50. Barbanti M, Todaro D, Costa G, et al. Opti-mized screening of coronary artery disease withinvasive coronary angiography and ad hoc percu-taneous coronary intervention during trans-catheter aortic valve replacement. Circ CardiovascInterv 2017;10:e005234.

51. Stewart BF, Siscovick D, Lind BK, et al. Clinicalfactors associated with calcified aortic valve dis-ease. Cardiovascular Health Study. J Am CollCardiol 1997;29:630–4.

52. Vilalta V, Asmarats L, Ferreira-Neto AN, et al.Incidence, clinical characteristics, and impact ofacute coronary syndrome following transcatheteraortic valve replacement. J Am Coll Cardiol Car-diovasc Interv 2018;11:2523–33.

53. Ducci A, Tzamtzis S, Mullen MJ, Burriesci G.Hemodynamics in the Valsalva sinuses aftertranscatheter aortic valve implantation (TAVI).J Heart Valve Dis 2013;22:688–96.

54. Makkar RR, Fontana G, Jilaihawi H, et al.Possible subclinical leaflet thrombosis in bio-prosthetic aortic valves. N Engl J Med 2015;373:2015–24.

55. Lugomirski P, McArdle B, Alak A, Dick A,Labinaz M. Late Presentation of left main coronaryartery impingement post-transcatheter aorticvalve replacement. J Am Coll Cardiol CardiovascInterv 2015;8:e159–60.

56. Ramirez R, Ovakimyan O, Lasam G, Lafferty K.A very late presentation of a right coronary arteryocclusion after transcatheter aortic valvereplacement. Cardiol Res 2017;8:131–3.

57. Soufras GD, Hahalis G, Kounis NG. Thromboticcomplications associated with transcatheter aorticvalve implantation: the role of Kounishypersensitivity-associated thrombotic syndrome.Cardiovasc Pathol 2014;23:383–4.

58. Blumenstein J, Kim WK, Liebetrau C, et al.Challenges of coronary angiography and inter-vention in patients previously treated by TAVI. ClinRes Cardiol 2015;104:632–9.

59. Allali A, El-Mawardy M, Schwarz B, et al.Incidence, feasibility and outcome of percuta-neous coronary intervention after transcatheteraortic valve implantation with a self-expandingprosthesis. Results from a single centerexperience. Cardiovasc Revasc Med 2016;17:391–8.

60. Chetcuti S, Kleiman NS, Matthews R,Popma JJ, Moore J. TCT-743: Percutaneous coro-nary intervention after self-expanding trans-catheter aortic valve replacement (abstr). J AmColl Cardiol 2016;68 Suppl B:B300–1.

61. Zivelonghi C, Pesarini G, Scarsini R, et al.Coronary catheterization and percutaneous in-terventions after transcatheter aortic valve im-plantation. Am J Cardiol 2017;120:625–31.

62. Boukantar M, Gallet R, Mouillet G, et al. Cor-onary procedures after TAVI With the self-expanding aortic bioprosthesis MedtronicCoreValve�, not an easy matter. J Interv Cardiol2017;30:52–62.

63. Htun WW, Grines C, Schreiber T. Feasibility ofcoronary angiography and percutaneous coronaryintervention after transcatheter aortic valvereplacement using a Medtronic� self-expandablebioprosthetic valve. Catheter Cardiovasc Interv2018;91:1339–44.

64. Tanaka A, Jabbour RJ, Testa L, et al. Inci-dence, technical safety and feasibility of coronaryangiography and intervention following self-expanding transcatheter aortic valve replace-ment. Cardiovasc Revasc Med 2019;20:371–5.

65. Yudi MB, Sharma SK, Tang GHL, Kini A. Coro-nary angiography and percutaneous coronaryintervention after transcatheter aortic valvereplacement. J Am Coll Cardiol 2018;71:1360–78.

KEY WORDS coronary artery disease,coronary computed tomographyangiography, fractional flow reserve, TAVR

APPENDIX For supplemental tables, pleasesee the online version of this paper.