Real World Single Center Experience With Saphenous Vein Grafts Interventions: Should Filters be Filtered out?

Abstract

BACKGROUND. Percutaneous coronary intervention (PCI) of saphenous vein grafts (SVG) can be challenging due to no reflow phenomenon from distal embolization of debris and microvascular vasoconstriction, resulting in myocardial injury post-procedure. Guidelines promote the use of distal embolic protection devices (EPD) to protect the distal arterial bed during SVG PCI. However, this approach has shown less-than-optimal results in many studies. We report our data using the Borgess protocol [prophylactic intracoronary (IC) nicardipine injection and direct stenting], as an alternative to EPDs in a large series of SVG interventions. METHODS. This is a retrospective, cohort study of our single center experience with SVG interventions between 2017 and 2021. The primary outcome of the study was major adverse cardiovascular events (MACE) [a composite of death, emergent coronary artery bypass graft surgery (CABG), myocardial infarction (MI), and target vessel revascularization (TVR)] at 30 days post-procedure. RESULTS. There were 424 consecutive SVG interventions performed during the study period, and 76% of cases presented with acute coronary syndrome. Full adherence to the Borgess protocol was observed in 36% of cases; IC nicardipine was utilized in 72% of cases. MACE rate was 3.5% at 30 days driven primarily by MI (2.6%). CONCLUSION. The Borgess protocol approach to vein graft interventions proved good outcomes when compared to SVG PCI in randomized trials utilizing EPDs. Our study is limited by the retrospective nature and single center experience.

J INVASIVE CARDIOL 2023;35(7). doi: 10.25270/jic/23.00089. Epub July 10

Key words: saphenous vein grafts, percutaneous coronary intervention, filter wire, distal embolic protection, nicardipine

Introduction

SVG PCI can be challenging due to no reflow phenomenon from distal embolization of debris and microvascular vasoconstriction, resulting in impaired thrombolysis in myocardial infarction (TIMI) flow, and possible myocardial injury post-procedure. The saphenous vein graft angioplasty free of emboli randomized (SAFER) trial showed 9% risk of no reflow in a control group that was reduced to 3% in the PercuSurge GuardWire group which translated to a decrease in MACE from 16.5% to 9% P=.004.¹ The Filterwire was then compared to the GuardWire and showed similar outcomes.² Consequently, the guidelines promoted the use of a filter wire to protect the distal arterial bed during SVG PCI.^3,4 However, this approach showed less-than-optimal results in many follow-up studies and subsequently, the guidelines revised their recommendations and decreased the COR evidence from I to IIa.^5,6

Given the conflicting data on SVG interventions, we developed our own method called the  Borgess protocol for vein graft interventions using IC nicardipine, pharmacologic prophylaxis, and direct stenting. This approach does not utilize filter wires or other mechanical distal protection. The initial encouraging results using this approach have been previously described.⁷ We report the results of this approach as an alternative to distal EPDs in a large consecutive series of all SVG interventions performed at Borgess Medical Center over a period of 4 years.

Methods

Study population. The electronic medical records (EMR) of all patients who underwent SVG interventions at Borgess Medical Center between June 2017 and February 2021 were included in the study. Patients who had interventions of the native vessel through the graft but without intervening on the vein graft were excluded. Left internal mammary artery (LIMA) and/or arterial grafts interventions were also excluded. Otherwise, all consecutive vein graft interventions were included. Multiple interventions on a single vein graft in the same procedure were counted as a one intervention, but patients who had multiple vein interventions during the same procedure were duplicated to address every vein intervention as a separate entity. A total of 424 consecutive vein graft interventions were studied. EMRs were reviewed to obtain patients’ characteristics, indication for the procedure, procedure details, and 30-day follow-up outcomes. The study complies with the Declaration of Helsinki and was approved by our local IRB.

Vein grafts interventions protocol – the Borgess protocol. The Borgess protocol for vein graft interventions was developed by the manuscript’s senior author and is the main method of vein graft intervention at our center. The protocol aims to minimize trauma to the graft as much as possible and enhance distal arteriolar vasodilatation to promote runoff and minimize no reflow. The technique is based on 2 fundamental procedural steps: (1) prophylactic IC nicardipine injection prior to stent delivery and again post-intervention, and (2) direct stenting without pre-dilatation to minimize downstream embolization.

Outcomes. The primary endpoint of the study was TIMI flow at the end of the procedure as documented in the procedure note. The secondary endpoint was 30-day MACE rate as defined per the SAFER trial,¹ the composite of death, MI, emergent bypass surgery, or target vessel revascularization (TVR) within 30 days of the index procedure. Death was defined as the occurrence of death from any cause. MI was determined based on cardiology evaluation at the time of assessment. MIs were defined according to the 3rd or 4th universal definition of MI depending on when the patient was seen during study time. Since not all interventions were performed completely following the Borgess protocol, the data were also assessed as a function of the adherence, or lack thereof, to the protocol. Given the retrospective descriptive nature of our study, we decided not to adjudicate any events. Finally, we compared our results to the historic data from the SAFER trial to better understand our outcomes.

Results

Baseline demographics. Approximately 424 consecutive SVG interventions were performed at our center within the study period by 10 operators and 15 interventional cardiology fellows. Patients’ characteristics are described in Table 1. The average SVG age was 14 years, and 36% of patients had cardiomyopathy with left ventricular ejection fraction (LVEF) <50%. There were 161 patients (38%) who had previous interventions with stents in the culprit SVG. The indication was stable angina in 24% of cases and acute coronary syndrome (ACS) in the remaining 76% [40% unstable angina, 34% non-ST-elevation MI (NSTEMI), and 2% with STEMI] (Figure 1).

Angiographic findings. The baseline findings are described in Table 2. The most common intervention was on SVG-OM (44%) followed by SVG-RCA (37%). Thrombus was angiographically reported in 6% of cases; 25% of cases included in-stent restenosis intervention (Table 2).

Procedure characteristics. IC nicardipine was given in 72% of cases with an average of 300 mcg per case; 52% of cases used nicardipine before PCI. Direct stenting was also performed in 52% of cases. Therefore, the Borgess protocol was completely followed in 36% of cases. A stent was implanted in 89% of cases and multiple stents were placed in 17%. Stents were post-dilated in 29% of cases. Aspiration or mechanical thrombectomy use was .9% and filter wire use was 4%. The most utilized stent was Xience (Abbott Vascular). The most common stent placement location was the body of the graft (46%), followed by the proximal/ostial part (31%), and the anastomosis of the native vessel in 26% of cases. Seventeen percent of patients had multiple stents at different locations of the same graft. TIMI III flow was achieved in 419/424 (99%) of cases (Figure 2).

Primary and secondary endpoints results. There were a total of 14 events (Table 3, Figure 3) within 30 days of PCI, 2 patients died (.4%) and no patient underwent emergent bypass surgery. There were 11 (2.6%) documented cases of MI within 30 days of the procedure and 2 cases of TVR (.4%), bringing total MACE at 30 days to 3.5%. Four patients treated according to the Borgess protocol had events (2 MIs and 2 deaths). There were 2 events with a thrombus present on angiogram before intervention (1 death and 1 MI). Nine cases with events were pre-dilated (7 had MIs and 2 TVRs) and 6 cases did not have nicardipine before the procedure (5 of them were pre-dilated as well). There were no reported events in cases that used filter wires (4% of all cases). Five events (30%) occurred in interventions on ISR (4 had MIs and 1 had TVR), none were treated according to the Borgess protocol (Table 4).

Discussion

Vein graft disease remains one of the major challenging entities in the field of interventional cardiology⁸ with some SVG PCI carrying a 5- to 20-fold higher risk of periprocedural complications compared to native coronary PCI.^8-10 In the early 2000s, the use of EPDs became the standard of care after the publication of the SAFER trial, which used the PercuSurge GuardWire system against conventional methods at the time.¹ Thereafter, since unprotected SVG PCI raised ethical concerns, multiple novel devices were tested against the PercuSurge system, such as the filter wire, and proved to be non-inferior.² The TRAP trial comparing the filter wire to none-EPD method was stopped prematurely after the PercuSurge system was approved.¹¹ Ultimately, in 2010/2011, the use of an EPD for all SVG PCI procedures where technically feasible was given a Class I recommendation by both the European Society of Cardiology and American College of Cardiology Foundation/American Heart Association PCI guidelines.^3,4 However, EPD use did not have major uptake in the real world,^10,12 peaking at 19% and 21% in some reports.^13,14 Observational studies and a large meta-analysis by TK Paul et al^12,13 showed worse outcomes with EPDs than what was shown in the randomized trials, including increased incidence of periprocedural MIs and procedural complications, such as no-reflow, dissection, and perforation. Another large study by Shoaib et al concluded that more contemporary data are needed for identification of the subset of patients who would gain the most benefit from EPD use in SVG PCI. Therefore, the European Society of Cardiology in 2018 followed by the American College of Cardiology Foundation/American Heart Association PCI guidelines in 2021 changed their class of recommendations to use EPD in vein graft interventions from class I to class IIa due to the conflicting data.^5,6

Our study is another addition to the large amount of observational data, which demonstrated that the use of EPDs may be unnecessary. We purposely defined our study endpoints to match those of the SAFER trial for easier comparison. In SAFER, of 801 eligible patients (406 patients in the EPD group vs 395 in the control group), the primary endpoint – a composite of death, MI, emergency bypass, or target lesion revascularization by 30 days – was observed in 65 patients (16.5%) assigned to the control group and 39 patients (9.6%) assigned to the EPD (P=.004) (GuardWire, Medtronic). This 42% relative reduction in MACE was driven by MI (8.6% versus 14.7%, P=.008) and no-reflow phenomenon (3% versus 9%, P=.02). TIMI III flow was achieved in 98% of the EPD group compared to 95% of the control group. It is important to note that MI was defined in the trial by the occurrence of an elevated CK-MB fraction >3x the upper limit of normal (standardized to each clinical site’s normal range) in at least 1 of 3 serial protocol-driven cardiac enzyme measurements performed during the first 18 to 24 hours after the index procedure or in any subsequent clinically driven measurement. Patients were then divided into Q wave vs non-Q wave MIs. Each group had 5 patients with Q wave MIs. The most significant difference was in the non-Q wave MI group that had CK-MB fraction 3-8 times the upper limit of normal; 19 patients in the GuardWire group vs 31 in the control group.

In comparison, our data show better outcomes using the Borgess protocol. A total of 424 consecutive vein graft interventions were performed between 2017 and 2021 by different operators. Even though the adherence to the Borgess protocol was low (36%), our outcomes are still better than what was reported in the SAFER trial. Our MACE rate is 3.5%, largely driven by the low number of reported MIs in the study. This correlates well with our current understanding of post-procedural MI and the use of troponin assays, which are more accurate and sensitive than the CK-MB used in the SAFER trial. Given the timing of our study, we believe the reported MIs were defined according to the 3rd or 4th universal definition of MI.^15,16 Additionally, the reported death or emergent bypass rate is much better compared to SAFER (.4% in our study compared to 1.0% in the SAFER GuardWire group and 2.8% in the SAFER control group). (Figure 4).

Another interesting observation in the current cohort is that 25% of the interventions were performed for ISR lesions, a subgroup that was not reported in the SAFER cohort. This is an important observation as it highlights the high prevalence of ISR in previous graft interventions. Although one would expect that the event rate should at least theoretically be lower in this cohort as compared to interventions involving de novo graft lesions, 5 of the 14 events occurred in this cohort, which is disproportionate to the overall event rate and highlights the fact that those graft ISR lesions should be assigned the same risk as de novo lesions. None of those patients adhered to the Borgess protocol, which was an operator decision.

Despite the lack of adherence to our protocol, we believe nicardipine use played a significant role in decreasing event rate and improving outcomes (72% of cases used IC nicardipine). Unlike nitroglycerin, which is predominately a venodilator, nicardipine is an arteriolar vasodilator, which helps carry the debris from the intervention out of the myocardium and into the venous system. It is also longer-acting than other arteriolar vasodilators such as adenosine. Our concept aims to minimize trauma to the vein graft as much as possible, hence we encourage direct stenting and prolonged inflations at modest pressure, to minimize any cheese-grade downstream effect. This is contrary to the use of filter wires, which usually requires pre-dilatation and manipulations of the graft without using pharmacologic distal protection. Additionally, EPD use is not always feasible, such as in small grafts or close to anastomosis. Therefore, our approach is a good alternative in those cases (Figure 5).¹⁷

Limitations. This is a single center observational study with very low usage of filter wires. The reported MIs were extracted from chart review and based on cardiology assessment at the time of consult. We did not adjudicate any events to avoid any bias in reporting the data. The SAFER trial data are over 2 decades old, and while some technology has evolved significantly over time, the EPDs remain similar without significant changes. The low adherence to the Borgess protocol was mostly driven by a lower percentage of direct stenting (52%), due to operators opting to pre-dilate before stent deployment. Nicardipine use at any time during PCI was 72% and pre-stenting was 52%. As explained in methodology, this is an observational retrospective study, the decisions during PCI were completely up to operator discretion without enforcing the Borgess protocol or any different approach. However, it is worth noting that lack of direct stenting correlated with 7/10 MI events (Table 4). TIMI flow post-op was collected by chart review due to lack of research funding to achieve complete independent and adjudicated review of all 424 interventions. Given the very low number of filter wires used (4%) without any hard outcomes in that group of patients, we decided not to exclude those patients from final analysis. 

Conclusion

Our study is another addition to the available observational data that suggests good outcomes can be achieved in SVG PCI without EPDs. In that capacity, a logical argument would suggest using simple techniques and widely available resources like the Borgess protocol instead of adding time and cost to the procedure with EPDs. However, it is important to point out that our data is observational and the single randomized trial that addressed this issue is over 2 decades old, with no apparent randomized trial on the horizon.

Affiliations and Disclosures

From the Ascension Borgess Hospital, Michigan State University & Western Michigan University, Kalamazoo, Michigan.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.

Manuscript accepted April 26, 2023.

Address for correspondence: Adnan Kassier, MD, Ascension Borgess Hospital, Michigan State University & Western Michigan University, 1521 Gull Rd, GOC 327, Kalamazoo, MI 49048. Email: Adnan.kassier@gmail.com

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