Short- and Mid-Term Outcomes of Complex and High-Risk Versus Standard Percutaneous Coronary Interventions in Patients Undergoing Transcatheter Aortic Valve Replacement

Abstract

Background. The prevalence of coronary artery disease (CAD) in patients undergoing TAVR varies and is associated with increased morbidity and mortality. We evaluated the outcomes of complex and high-risk percutaneous coronary interventions (CHIP-PCIs) and TAVR compared with standard PCI and TAVR. Between January 2014 and March 2021, a total of 276 consecutive patients with severe aortic stenosis (AS) who underwent TAVR and PCI at 3 centers within Northwell Health were retrospectively reviewed. CHIP-PCI was defined as PCI with one of the following: left ventricular ejection fraction (LVEF) <30%; left main coronary artery (LMCA)/chronic total occlusion (CTO) intervention; atherectomy; or need for left ventricular (LV) support. One hundred twenty-seven patients (46%) had CHIP-PCI prior to TAVR and 149 patients (54%) had standard PCI. Thirteen percent of CHIP-PCI and 22% of standard PCI cases were done concomitantly with TAVR. CHIP-PCI criteria were met for low EF (19%), LMCA (25%), CTO (3%), LV support (20%), and atherectomy (50%). The types of valves used were similarly divided (49% balloon expandable vs 51% self expanding. Major adverse cardiac or cerebrovascular event (MACCE) rate for CHIP-PCI/TAVR was 4.9% at 30 days vs 1.3% for standard PCI/TAVR (P=.09), driven by in-hospital stroke. At 1 year, the rates of MACCE for CHIP-PCI/TAVR remained higher than for standard PCI/TAVR, but was not statistically significant (8.7% vs 4%; P=.06), driven by revascularization. We found no differences between major and/or minor vascular complications. New York Heart Association classification at 1 month was similar (I/II 93% vs 95%; P=.87). Our study suggests that CHIP-PCI can be safely performed in patients with complex CAD and concomitant severe AS.

Keywords: CHIP-PCI, severe aortic stenosis, TAVR

The prevalence of coronary artery disease (CAD) in patients undergoing transcatheter aortic valve replacement (TAVR) ranges between 15%-80% and is associated with increased morbidity and mortality.^1,2 In current practice, severe and proximal CAD is treated prior to TAVR.³ As age and comorbidities increase, so does the complexity of percutaneous coronary intervention (PCI).⁴ As the complexity of CAD increases, there is a shift to favoring coronary artery bypass grafting (CABG) and surgical aortic valve replacement (SAVR) over PCI and TAVR. Yet, many of these patients are not ideal surgical candidates due to age and comorbidities. Therefore, we evaluated the outcomes of complex and high-risk PCI (CHIP-PCI) and TAVR compared with standard PCI and TAVR.

Methods

Between January 2014 and March 2021, a total of 276 consecutive patients with severe aortic stenosis (AS) who underwent PCI and TAVR at 3 metropolitan centers within Northwell Health were retrospectively reviewed (Figure 1). Patients were included if there was a planned coronary intervention and aortic intervention within 6 months of one another.

CHIP-PCI was defined as PCI with 1 of the following: left ventricular ejection fraction (LVEF) <30%; left main coronary artery (LMCA) intervention, atherectomy, chronic total occlusion (CTO) intervention; and/or need for left ventricular (LV) support (Impella percutaneous left ventricular assist device [Abiomed] or intra-aortic balloon pump). The combined major adverse cardiovascular and cerebrovascular event (MACCE) rate among patients who underwent CHIP-PCI and TAVR was compared with the rate among patients who underwent standard PCI and TAVR during the same period. MACCE was defined as mortality, myocardial infarction, repeat revascularization, and stroke in-hospital to 30 days. Clinical outcomes at 1 year from TAVR were also compared. Individual adverse event rates for all-cause mortality, revascularization, and stroke rates were determined. Vascular complications were defined by the Valve Academic Research Consortium (VARC) criteria. The study protocol was approved by the institutional review board. All data were de-identified and informed consent was waived.

Statistical analysis. Statistical analysis was performed with normally distributed continuous variables summarized using data expressed as mean ± standard deviation, and non-normally distributed continuous variables as medians. Categorical data are presented as frequency counts and percentages. Comparisons between groups were performed using 2-sample t test, Chi-square test, and Fisher’s exact test, as appropriate. All statistical analyses were performed with GraphPad software.

Results

Of the 276 patients who underwent PCI/TAVR, CHIP-PCI prior to TAVR was performed in 127 patients (46%) and standard PCI prior to TAVR was performed in 149 patients (54%). Seventeen patients (13%) in the CHIP-PCI group and 33 patients (22%) in the standard PCI group were done concomitantly with TAVR (P=.74). The mean age was 83 ± 10.6 years, with the majority of patients (58%) male (Table 1). Baseline Society of Thoracic Surgeons (STS) score of 6.5 ± 4% suggests that our patients were of intermediate or high surgical risk. Patients who received CHIP-PCI and TAVR had similar baseline demographics, but were more likely to be smokers, have prior myocardial infarction, have significant peripheral vascular disease, a lower average ejection fraction (EF), higher rates of cardiovascular implantable electronic devices, and a higher STS score.

Among patients who received CHIP-PCI, the criteria met to reach the definition of CHIP-PCI were as follows: low EF (19.6%), LMCA-PCI (19.6%), CTO (3%), use of LV support (9.4%), and atherectomy (48%). In the CHIP-PCI/TAVR group, 36.2% of patients had balloon aortic valvuloplasty (BAV) prior to PCI vs only 24.2% of patients in the standard PCI/TAVR group (P=.03). The types of valves used were equally divided (49% balloon expandable vs 51% self expanding). The mean number of coronary lesions treated was 1.2 (Table 2).

In-hospital and 30-day outcomes post TAVR were similar between the 2 groups (Table 3). MACCE rate at 30 days was 4.9% in the CHIP-PCI group vs 1.3% in the standard PCI/TAVR group (P=.09). There were 2 deaths in the CHIP-PCI/TAVR group (1 patient in-hospital and 1 patient between discharge and 30 days). Five patients (3 in the CHIP-PCI/TAVR group vs 2 in the standard PCI/TAVR group) had ischemic strokes post TAVR (P=.53). There were no significant differences between major and/or minor vascular complications during TAVR. New York Heart Association (NYHA) I/II classification at 1 month was similar between the 2 groups (93% in the CHIP-PCI/TAVR group vs 95% in the standard PCI/TAVR group; P=.87)

There was a trend to higher 1-year MACCE rates, although not statistically different, in the CHIP-PCI/TAVR group vs the standard PCI/TAVR group (8.7% vs 4%, respectively; P=.06), driven by repeat revascularization rates (3.9% vs 2%, respectively; P=.36) (Table 4). All-cause mortality rates were 2.4% for CHIP-PCI/TAVR vs 0.7% for standard PCI/TAVR (P=.26). Rates of myocardial infarction were comparable as well (2.4% for CHIP-PCI/TAVR vs 1.3% for standard PCI/TAVR; P=.53). Rates of moderate to severe paravalvular leak were not different between the 2 groups (3.9% for CHIP-PCI/TAVR vs 2% for standard PCI/TAVR; P=.36). Only 1 patient required a valvular reintervention after CHIP-PCI/TAVR due to hemolysis from PVL.

Discussion

The treatment of CAD in patients undergoing TAVR remains a controversial topic due to the lack of definite data on the need to revascularize hemodynamically significant coronary lesions found during preprocedural work-up.^5,6 Current guidelines recommend revascularizing severe (>70%) coronary lesions located in proximal coronary segments and >50% stenosis of the LMCA before TAVR.⁷ In patients with intermediate or high SYNTAX scores, the combination of SAVR/CABG is recommended over TAVR/PCI.⁸ However, in patients with low SYNTAX scores who have complex single-vessel disease requiring revascularization, or in patients with high SYNTAX scores combined with intermediate or high surgical risk, the optimal strategy is still under debate.

Data regarding LMCA revascularization and TAVR are limited. One observational study reported the feasibility of LMCA percutaneous revascularization pre-TAVR, though this was based on a high-risk cohort (mean STS score of 8.1) with limited follow-up.⁹ Moreover, patients with high SYNTAX scores and/or LMCA disease were excluded from the randomized studies comparing TAVR with SAVR.⁸ Comparing our patient population with that of the PARTNER, U.S. CoreValve High Risk Study, SURTAVI, and Evolut Low Risk trials suggests that our CHIP-PCI/TAVR patient panel fell into the high surgical risk category based on comorbidities and STS scores.^10-16 The standard PCI/TAVR patients would be considered intermediate risk. These differences in risk categories were likely the driver of higher rates of MACCE in the CHIP-PCI/TAVR population during a follow-up period of 1 year. However, the difference in rates was not statistically significant. We also found slightly higher rates of vascular complications in patients who had TAVR + CHIP-PCI during their valve replacement. However, this observed difference was also not statistically significant.

In the present study, the MACCE rates at 30 days were higher in the CHIP-PCI/TAVR patients, yet not statistically significant, driven by a difference in death and stroke rates. The in-hospital mortality was a single patient who developed asystole upon arrival to telemetry post TAVR. Autopsy was not performed, but the etiology was believed to be secondary to complete heart block without an escape rhythm and inability to resuscitate. The second mortality occurred at home and the cause of death was unknown. Conversely, the MACCE rates at 1 year were driven by repeat revascularization. The rate of revascularization was numerically higher in the CHIP-PCI/TAVR group, but was not statistically significant compared with the standard PCI/TAVR group. This finding raises the question of the necessity for complete revascularization while also suggesting that TAVR can be performed safely prior to CAD treatment with subsequent PCI despite the potential difficulties of coronary re-access.

While the low frame height and open-cell geometry of the Edwards balloon-expandable valve (Edwards Lifesciences) promote access to coronary ostia, coronary re-access can still be an issue in cases where the coronary heights are low. On the other hand, positioning of the CoreValve self-expanding valve (Medtronic) to ensure commissural alignment has improved coronary re-access for these valves.¹⁷ Nonetheless, coronary interventions after TAVR remain a challenge, exposing patients to higher amounts of radiation and contrast for percutaneous interventions. This challenge is especially true if self-expanding valves are implanted high in order to lower the risk of conduction abnormalities.¹⁷ Newer valves, such as the Acurate Neo (Boston Scientific) or Portico (Abbott) have tried to address the issue of re-access via their designs. The Acurate Neo valve may provide easier access to the coronary arteries due to its open stabilizing arches and low metal-to-artery ratio, but this valve failed to show non-inferiority to the Edwards Sapien and Evolut CoreValve.^18,19 The large cell area of the Portico valve and its annular positioning facilitate coronary engagement, but the tall frame height can be challenging. Other developments in the field, such as dedicated catheters that conform to the constrained space within a transcatheter valve frame, may also overcome some of the current shortcomings and facilitate coronary engagement.

The optimal timing of coronary revascularization remains uncertain in patients undergoing TAVR. Small or single-center studies have shown that performing PCI prior to TAVR does not increase the risk of adverse outcomes post TAVR. The PUREVALVE registry included 191 consecutive patients, 39 of whom had PCI prior to TAVR.²⁰ Overall, 30-day mortality did not differ significantly between patients with or without CAD (5.7% vs 2.9%; P=.32), although there were numerically higher rates of myocardial infarction (4.4% vs 0%; P=.08) and major stroke (2.7% vs 0%; P=.14) in the CAD group. The BERN-TAVI registry included 165 patients with severe AS and obstructive CAD.²¹ Fifty-nine patients underwent PCI (23 patients prior to TAVR and 36 patients concomitantly with TAVR). 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=.24), major stroke (4.1% vs 3.4%; P>.99), and VARC combined safety endpoint (31.0% vs 23.7%; P=.33). Both studies were limited by the number of patients.

Most of the coronary interventions in our patient population were performed prior to TAVR. Only 13% of the PCIs in the CHIP-PCI/TAVR group and 22% of the PCIs in the standard PCI/TAVR group were performed at the same time as the valve replacement. Our study, therefore, confirms previously published data and provides insight to the fact that the presence of complex anatomy should not deter interventions prior to TAVR. Barbanti et al showed comparable results in their prospective study, where 40% of the patients with severe CAD underwent concomitant TAVR and PCI without a significant increase in vascular complications or mortality/morbidity outcomes.²² Patients in that study were almost twice as likely to have concomitant PCI and TAVR if the anatomy was not complex. This would support both procedures performed concomitantly to decrease the number of interventions in selected patients.

The overall rate of BAV prior to PCI in our study was ~30%. The rate of BAV was higher in the CHIP-PCI/TAVR group vs the standard PCI/TAVR cohort (36.2% vs 24.2%; P=.03). The suggested trend was that if the LVEF was >40%, those patients did not have BAV prior to PCI. The 9 patients who had a percutaneous LV assist device placed had BAV prior to PCI. Two out of 3 mortalities in the CHIP-PCI cohort at 1 year had BAV prior to PCI. Both patients had complex substrates with numerous comorbidities. Half of the minor vascular complications in the CHIP-PCI group were in patients who had BAV with PCI prior to TAVR. This finding is hypothesis generating and suggests that having BAV requiring large-bore transfemoral access puts a patient at risk for vascular complications. Our contemporary rates of vascular complications have decreased due to an increased use of lower-profile Vida and Bard valvuloplasty balloons (BD) and modified vascular management techniques. Our rates of vascular complications for this patient population were overall low. A larger patient population would be helpful to further investigate the effect of BAV on access-site issues for CHIP-PCI patients.

The sample size of our study was limited for the evaluation of some infrequent outcomes (ie, stroke or myocardial infarction), and a type II statistical error could not be excluded in such cases. Large, prospective studies specifically designed to assess the issue of the optimal treatment for patients with severe AS and concomitant complex CAD are needed to shed more light on this issue. This study does not address drop-out of patients who received PCI prior to TAVR and subsequently did not return for TAVR either due to mortality post PCI, increase in procedural risks after PCI preventing TAVR, or lack of follow-up post PCI.

Furthermore, it would be interesting to compare the outcomes of these patients with those who undergo CABG and TAVR either as separate procedures or as part of a combined hybrid off-pump CABG and direct aortic TAVR in patients without appropriate transfemoral access. For patients with an intermediate or low surgical risk, these 2 approaches could provide alternatives to PCI.

Conclusion

Patients with complex coronary disease and concomitant severe AS present a management challenge. The optimal timing for each intervention is not known and often depends on the patient’s clinical status and comorbid conditions. Our study suggests that performing CHIP-PCI and TAVR in severe AS patients from varied risk profiles could be safe and successful whether PCI is performed either at the same time as, or prior to, TAVR. Further studies are needed to validate our results and provide additional evidence to support such complex multimodality treatments.

Affiliations and Disclosures

From the ¹Department of Cardiovascular & Thoracic Surgery, Lenox Hill Hospital/Northwell Health, New York, New York; ²Department of Cardiovascular & Thoracic Surgery, Staten Island University Hospital/Northwell Health, New York, New York; ³Department of Cardiovascular & Thoracic Surgery, South Shore University/Northwell Health, New York, New York; and ⁴Department of Cardiovascular & Thoracic Surgery, North Shore University/Northwell Health, New York, New York.

^aThe Northwell TAVR Investigators comprise Derek Brinster, MD¹; Alan Hartman, MD⁴; Mohammed Imam, MD²; Elana Koss, MD⁴; Priti Mehla, MD¹; Efstathia Mihelis, PA-C¹; Azhar Supariwala, MD³; and Sridhar Uttar, MD¹

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Kliger, Dr Pirelli, and Dr Rutkin report that they are consultants and receive speaking honoraria from Edwards Lifescience and Medtronic. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript accepted September 16, 2022.

Address for correspondence: Chad Kliger, MD, Department of Cardiovascular & Thoracic Surgery, Lenox Hill Hospital/Northwell Health, 130 East 77th Street, 4th floor, New York, NY 10075. Email: ckliger@northwell.edu

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