Author + information
- Received January 28, 2013
- Revision received April 12, 2013
- Accepted April 18, 2013
- Published online August 1, 2013.
- Nicolas M. Van Mieghem, MD∗∗ (, )
- Robert M. van der Boon, MSc∗,
- Elhamula Faqiri, MSc∗,
- Roberto Diletti, MD∗,
- Carl Schultz, MD, PhD∗,
- Robert-Jan van Geuns, MD, PhD∗,
- Patrick W. Serruys, MD, PhD∗,
- Arie-Pieter Kappetein, MD, PhD†,
- Ron T. van Domburg, PhD∗ and
- Peter P. de Jaegere, MD, PhD∗
- ∗Department of Interventional Cardiology, Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands
- †Department of Cardio-thoracic surgery, Thoraxcenter, Erasmus Medical Center, Rotterdam, the Netherlands
- ↵∗Reprint requests and correspondence:
Dr. Nicolas M. Van Mieghem, Department of Interventional Cardiology, Thoraxcenter, Erasmus Medical Center, Room Bd 171, ‘s Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands.
Objectives This study sought to assess in patients undergoing transcatheter aortic valve implantation (TAVI), the prevalence and impact of incomplete coronary revascularization defined as >50% coronary artery or graft diameter stenosis on visual assessment of the coronary angiogram.
Background TAVI is an established treatment option in elderly patients with aortic stenosis (AS) and a (very) high operative risk. Coronary artery disease (CAD) is often associated with AS.
Methods A single-center cohort of consecutive patients undergoing TAVI between November 2005 and June 2012 was evaluated for the presence of significant CAD. The decision to revascularize and pursue complete revascularization was made by heart team consensus.
Results A total of 263 consecutive patients with a mean age of 80 ± 7 years and 51% male underwent TAVI with a median follow-up duration of 16 months (interquartile range: 4.2 to 28.1 months). Significant CAD with myocardium at risk was present in 124 patients (47%), 44 of whom had had previous coronary artery bypass grafting (CABG), and the median SYNTAX score in the 81 patients without previous CABG was 9.00 (2.38 to 15.63). Staged percutaneous coronary intervention (PCI) was planned in 19 (15%) and concomitant PCI with TAVI in 20 (16%). The median post-procedural residual SYNTAX score of patients without prior CABG was 5.00 (0.13 to 9.88). Overall, 99 patients (37%) (61 with no CABG and 38 CABG patients) had incomplete revascularization after TAVI. Revascularization status did not affect clinical endpoints. Kaplan-Meier survival curves for patients with and without complete revascularization demonstrated a 1-year mortality of 79.9% versus 77.4% (p = 0.85), respectively.
Conclusions In an elderly patient population undergoing TAVI for severe AS, a judicious revascularization strategy selection by a dedicated heart team can generate favorable mid-term outcome obviating the need for complete coronary revascularization.
Transcatheter aortic valve implantation (TAVI) is increasingly offered as a less invasive treatment option for elderly patients with symptomatic aortic valve stenosis (AS) at higher operative risk (1–5). Degenerative aortic valve disease shares similar risk factors with atherosclerotic coronary artery disease (CAD), and patients with symptomatic AS often have concomitant CAD (6–9). In surgical series, the presence of significant CAD increases the operative risk and mortality of surgical aortic valve replacement (SAVR), both when left untreated and when treated with concomitant coronary artery bypass grafting (CABG) (10–13). According to guidelines on valvular heart disease, concomitant CAD should be treated while performing SAVR (14,15). The impact of CAD in patients undergoing TAVI is not well established. In the randomized PARTNER (Placement of Aortic Transcatheter Valves) trial, patients with significant CAD requiring revascularization therapy were excluded from the trial (16,17). Retrospective TAVI studies remain equivocal but tend to suggest that presence of CAD or non-revascularized myocardium is not associated with worse outcome (18–23).
The SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) trial introduced the SYNTAX score to assess the extent and complexity of significant CAD (24). Incomplete revascularization was associated with worse outcome. Furthermore, in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI), a residual SYNTAX score to evaluate untreated lesions also predicts short- and longer-term prognosis (25). The aim of this study was to assess the prevalence and impact of incomplete revascularization in patients undergoing TAVI.
The study population consisted of all consecutive patients with symptomatic severe AS who underwent TAVI between November 2005 and June 2012 in the Erasmus Medical Center, Rotterdam, the Netherlands. All potential TAVI candidates underwent a detailed multidisciplinary and multimodality imaging assessment. Over the course of the TAVI program, a dedicated heart team was installed consisting of at least 1 interventional cardiologist, 1 cardiac surgeon, and 1 imaging specialist and was completed with an anesthesiologist, geriatrician, or neurologist upon indication. The heart team convened on a weekly basis and confirmed a patient's eligibility for TAVI based on a critical appraisal of established risk scores (STS, Logistic EuroSCORE), assessment of risk variables not included in these models, anatomical considerations, and clinical judgment. In principle, patients needed to be at high or prohibitive operative risk. Invasive coronary angiography was mandatory in all patients and was assessed in the heart team discussion. In case of significant CAD (i.e., >50% diameter stenosis on visual assessment of the coronary angiogram), the treatment strategy and completeness of revascularization was determined based on consensus decision before the TAVI procedure, taking into consideration infarcted area, viable myocardial tissue at risk, and technical complexity. Myocardium at risk was not formally quantitated by myocardial imaging but was estimated by visual assessment of the presence of obstructive atherosclerotic disease in coronaries supplying noninfarcted myocardial territories. The revascularization options were: 1) staged PCI before the TAVI procedure; 2) PCI concomitant with the TAVI procedure; and 3) conservative approach (no PCI).
Baseline characteristics, procedural data, and outcome data were prospectively collected in a dedicated database in accordance with local institutional review board guidelines. All in-hospital clinical endpoints are defined according to the Valve Academic Research Consortium criteria (26). Per protocol, clinical follow-up visits were scheduled at 6 weeks, 6 months, 12 months, and yearly thereafter. Survival was obtained from the Dutch Civil Registry. Clinical follow-up was derived by reviewing hospital charts and contacting referring physicians and patients' general practitioners.
For the purpose of this study, all baseline diagnostic angiograms were re-assessed to capture baseline coronary status. Distinction was made between patients with and without previous CABG. In patients with previous CABG, completeness of revascularization was assessed by evaluating the native coronary circulation and the respective grafts. For patients without previous CABG, including those with prior PCI, the SYNTAX score was calculated. In patients with significant CAD after the previous CABG, or a SYNTAX score >0, treatment strategy was documented as staged intervention, concomitant intervention, or no intervention. After the TAVI procedure, the completeness of revascularization was re-assessed: a residual SYNTAX score was calculated in the no-CABG cohort. During follow-up, the need for additional coronary interventions, indication (elective or acute coronary syndrome), and success of PCI after TAVI was assessed.
TAVI procedural details have been extensively described before (27). During the TAVI procedure, all patients were on full-dose aspirin and clopidogrel. Patients were loaded with 300 mg of aspirin and 300 mg of clopidogrel 1 day before the TAVI. Procedural anticoagulation was obtained with a heparin bolus of 70 IU/kg, aiming for an activated clotting time of 250 to 300 ms. The 2 commercially available TAVI platforms, the Medtronic CoreValve system (Medtronic, Minneapolis, Minnesota) and the Edwards SAPIEN valve (Edwards Lifesciences, Irvine, California), were used. The transfemoral approach was the access strategy of first choice, followed by the transaxillary and transapical routes. PCI was executed according to standard practice and always before the actual valve implantation. Drug-eluting stents were the stent platform of first choice, and patients continued dual antiplatelet therapy for 1 year after PCI.
Categorical variables are presented as frequencies and percentages, and were compared with the use of the Pearson chi square test or the Fisher exact test, as appropriate. Continuous variables are presented as mean ± SD (in case of a normal distribution) or median (interquartile range [IQR]) (in case of a skewed distribution) and compared with the use of the Student t test or the Mann-Whitney U test. Normality of the distributions was assessed using the Shapiro-Wilks test. Kaplan-Meier curves were generated to assess estimates of survival. A 2-sided alpha level of 0.05 was used for all superiority testing. All statistical analysis were performed with the use of SPSS software version 17.0 (SPSS, Chicago, Illinois).
A total of 263 consecutive patients underwent TAVI with a median follow-up duration of 16 months (IQR: 4.2 to 28.1 months). Baseline and procedural characteristics are displayed in Tables 1 and 2: mean age was 80 ± 7 years, and 51% were male. Mean Logistic EuroSCORE was 17.63 ± 10.41%; a transfemoral percutaneous access strategy was used in 95% of patients. The Medtronic CoreValve was the predominant device platform. Two-thirds of all patients (175 of 263 patients) had a history of past or current CAD with previous PCI or CABG in 28% and 27%, respectively, of the patients and a previous myocardial infarction in 25%. At baseline, obstructive atherosclerotic disease in coronary arteries supplying noninfarcted myocardial territories was present in 124 patients (47%), 44 of whom (35%) had had previous CABG. Nine patients initially presented with an ACS: 6 with unstable angina/non–ST-segment elevation myocardial infarction and 3 with ST-segment elevation myocardial infarction. Male sex, hypertension, chronic kidney disease, and low left ventricular ejection fraction were more prevalent in patients with incomplete revascularization at baseline.
All patients who initially presented with an ACS were treated with ad hoc PCI followed by TAVI at least 1 week after PCI. Of the 70 patients with prior CABG, 44 (63%) had incomplete revascularization at the time of heart team presentation because of progressive native CAD or saphenous vein graft disease. Revascularization was planned in 6 (14%): staged PCI in 5 and concomitant with the TAVI procedure in 1. All 6 patients obtained complete revascularization (Fig. 1). A total of 80 patients with no history of prior CABG had incomplete revascularization at baseline, with a median SYNTAX score of 9.00 (2.38 to 15.63). PCI TAVI was planned in 33 patients (41% of patients with a SYNTAX score >0): staged in 14 (17%) and concomitant with TAVI in 19 (24%). The median residual SYNTAX score after TAVI was 5.00 (0.13 to 9.88). The change in SYNTAX score in the no-CABG patients who were planned for PCI and were incompletely revascularized is shown in Figure 2. Overall, 99 patients (38%) (61 with no-CABG and 38 CABG patients) were incompletely revascularized after TAVI.
Clinical follow-up was complete for all patients. Table 3 illustrates the clinical endpoints subcategorized according to the presence of incomplete revascularization. There were no relevant differences among the respective cohorts. Procedural time and total contrast volume were similar. There were no differences in cardiac enzyme rise between patients with or without CAD, or whether patients obtained complete revascularization or not. Remarkably, during follow-up, no evident residual angina was noted. Survival curves for patients with and without complete revascularization at baseline or after TAVI, and for patients with residual SYNTAX score <8 versus ≥8 are displayed in Figure 3. No significant differences were found in overall survival.
Eight patients underwent PCI a median of 140 days (IQR: 0 to 337 days) after TAVI. All except 1 were prior Medtronic CoreValve cases. Two patients had no CAD (SYNTAX score = 0) before the TAVI procedure, and 5 patients had accepted incomplete revascularization (3 after previous CABG). One patient with staged left main coronary artery PCI had a late stent thrombosis 126 days after TAVI while still on dual antiplatelet therapy. One patient had a TAVI procedure–related dissection of the left main stem and underwent intravascular ultrasound–guided PCI 1 day after TAVI (28). One patient presented with a troponin rise, yet the coronary angiogram and intravascular ultrasound examination showed no obvious disease progression. Pragmatically, a balloon dilation was performed on the known ostial right coronary artery lesion. Two patients presented with a ST-segment elevation myocardial infarction: 1 with an acute occlusion of a saphenous vein graft, the other with a de novo thrombotic occlusion of the proximal left anterior descending coronary artery. Two PCI procedures were complicated by a neurological event (1 major stroke, and 1 transient ischemic attack).
Our study on 263 consecutive elderly high-risk TAVI patients highlights: 1) incomplete coronary revascularization at baseline is common; 2) revascularization strategy based on heart team consensus is feasible; and 3) when revascularization strategy is based on heart team consensus, complete revascularization is not a prerequisite for good medium-term prognosis.
Prevalence of CAD in patients with AS
The prevalence of significant CAD in our study is similar to what has been reported in other TAVI registries, yet appears somewhat higher than what is reported in the surgical literature, indicating CAD in 30% to 50% of patients who undergo SAVR (20,22). An overall older study population and the fact that patients with advanced comorbidities may also have more CAD may explain a higher prevalence of CAD in current TAVI practice. Also, patients with antecedents of complex CAD, including previous revascularization therapies, may be driven in the direction of TAVI.
Treatment strategy for AS in combination with CAD
Data on the need for combined CABG with SAVR in case of severe AS with concomitant significant CAD are relatively scarce but seem to suggest its merits (13,29). Concomitant CABG may improve short- and long-term survival, and reduce the risk for perioperative myocardial infarction (30,31). As such, it has been adopted in international guidelines on valvular heart disease (14,15). Conversely, a cohort study from the Northern New England Cardiovascular Disease Study Group on 7,584 consecutive patients undergoing SAVR suggested concomitant CABG did not impact survival in octogenarians as opposed to patients <80 years of age (32). These findings are corroborated by Maslow et al. (33), confirming there was no difference in long-term survival between isolated SAVR and SAVR combined with CABG in octogenarians.
A pooled analysis of 2 TAVI feasibility registries including 201 high-risk patients suggested that a history of previous cardiovascular intervention was associated with increased short- and long-term mortality and a more than 2 times higher risk of dying at any point (21). However, no data from invasive coronary angiograms were available, and concomitant PCI and TAVI was not allowed. In the early Vancouver experience of 136 patients, 76% had coexisting CAD. Presence of CAD or non-revascularized myocardium as determined by the Duke Myocardial Jeopardy score was not associated with an increased risk of adverse events up to 1 year (23).
The Italian CoreValve Registry enrolling 663 consecutive patients with previous PCI or CABG in 38% of cases did not find any impact of previous coronary intervention on 1-year clinical outcome (19). The German TAVI Registry, including 1,382 patients (82% CoreValve) with CAD (defined as angiographically determined coronary stenosis ≥50%) present in 62%, did not discriminate between patients who underwent PCI in preparation for TAVI (staged PCI) or with a past history of PCI (20). Patients with CAD had a lower ejection fraction and a greater proportion of ejection fraction <30%. Concomitant PCI was performed in only 5.5% of patients with CAD. By multivariate analysis, CAD was not associated with in-hospital mortality.
A single-center experience including 125 patients adopted a strategy of PCI of all significant epicardial lesions before TAVI. Fifty-five patients required PCI, all but 3 as a staged procedure with a median time interval between PCI and TAVI of 10 days (34). No data were provided on PCI success and actual completeness of revascularization. The need for PCI was not associated with 30-day or 6-month adverse event rates.
The timing of elective PCI in patients planned for TAVI is essential in the heart team decision-making process and requires consideration of patient characteristics (age, frailty, renal function, etc.) and procedural complexity. In comparison with concomitant PCI and TAVI, a 2-step approach may result in relative reduction in procedure time and radiation and contrast exposure, yet demands arterial access twice with the inherent risk for vascular and bleeding complications and may come with additional hospitalization costs.
Our strategy on concomitant CAD with TAVI reflects what has been reported by the Bern group. In the Bern TAVI registry on 265 TAVI patients, 65% had CAD, defined as a significant stenosis >50% or previous revascularization therapy, 35% of whom underwent staged (n = 23 patients) or concomitant (n = 36) PCI (22). PCI in addition to TAVI did not have an impact on outcome. Also, patients with significant CAD who did not undergo PCI had similar outcomes as compared with TAVI in patients without CAD. No information was provided related to completeness of revascularization in patients undergoing staged or concomitant PCI. We used the residual SYNTAX score to characterize residual stenosis after PCI. The median post-procedural residual SYNTAX score of patients without prior CABG was 5.00 (0.13 to 9.88). Complete revascularization was achieved in 20% of TAVI patients with incomplete revascularization at baseline. The residual SYNTAX score may help in risk stratifying patients for future coronary events. In moderate- to high-risk ACS patients, a residual SYNTAX score (rSS) >8 was associated with poor 30-day and 1-year survival (25). We could not detect any impact of the residual SYNTAX score in our series. In principle, ACS and TAVI populations differ significantly because in the latter, there is no acute clinical event and patients are older. The importance of age on the impact of incomplete revascularization has been suggested in a French study on patients undergoing CABG, which found incomplete revascularization did not have an impact on survival in patients >60 years of age, suggesting that in this particular elderly patient population at high operative risk, limited coronary revascularization may be considered when deemed necessary (35). It may be safe to waive variable degrees of CAD without intervention, and pursuit of complete revascularization is not a prerequisite for medium-term clinical success in an elderly AS patient population, provided a rational and pragmatic approach to CAD by a dedicated heart team is guaranteed. Finally, using this selective revascularization strategy, the urge for PCI after TAVI is limited, and although it is technically feasible, may be associated with associated morbidity as suggested by 2 neurological events in our series.
In this single-center study, extent and complexity of CAD were assessed by retrospectively calculating the SYNTAX score, yet baseline characteristics and clinical endpoints were prospectively collected. Scoring relied exclusively on visual assessment of the diagnostic angiograms. Fractional flow reserve was only used in a minority of cases but may certainly downgrade the extent of CAD. The median follow-up duration of 16 months provides insights into the impact of CAD in the mid-term, yet precludes extrapolation to longer-term follow-up. Given the relatively small sample size, our data should be interpreted with caution and demand confirmation in larger (preferably randomized) studies.
In an elderly patient population undergoing TAVI for severe AS, incomplete coronary revascularization is a dominant baseline feature. Judicious revascularization strategy selection by a dedicated heart team can generate favorable mid-term outcomes, obviating the need for complete coronary revascularization.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- acute coronary syndrome
- aortic valve stenosis
- coronary artery bypass grafting
- coronary artery disease
- interquartile range
- percutaneous coronary intervention
- surgical aortic valve replacement
- transcatheter aortic valve implantation
- Received January 28, 2013.
- Revision received April 12, 2013.
- Accepted April 18, 2013.
- American College of Cardiology Foundation
- Bosmans J.M.,
- Kefer J.,
- De Bruyne B.,
- et al.
- Tamburino C.,
- Capodanno D.,
- Ramondo A.,
- et al.
- Moat N.E.,
- Ludman P.,
- de Belder M.A.,
- et al.
- Zahn R.,
- Gerckens U.,
- Grube E.,
- et al.
- Otto C.M.,
- Kuusisto J.,
- Reichenbach D.D.,
- Gown A.M.,
- O'Brien K.D.
- Bonow R.O.,
- Carabello B.A.,
- Chatterjee K.,
- et al.,
- American College of Cardiology/American Heart Association Task Force on Practice Guidelines
- Vahanian A.,
- Alfieri O.,
- Andreotti F.,
- et al.
- Ussia G.P.,
- Barbanti M.,
- Colombo A.,
- et al.
- Genereux P.,
- Palmerini T.,
- Caixeta A.,
- et al.
- Leon M.B.,
- Piazza N.,
- Nikolsky E.,
- et al.
- Mullany C.J.,
- Elveback L.R.,
- Frye R.L.,
- et al.
- Hwang M.H.,
- Hammermeister K.E.,
- Oprian C.,
- et al.
- Likosky D.S.,
- Sorensen M.J.,
- Dacey L.J.,
- et al.