Abstract
Background
Saphenous vein graft (SVG) percutaneous coronary intervention (PCI) carries a high-risk of slow or no-reflow (SNR)—up to 15% in stable ischemia and 29% in acute coronary syndrome (ACS)—leading to higher major adverse cardiovascular event rates. Evidence on high-dose intracoronary adenosine for SNR prevention remains limited.
Methods
We analyzed 171 patients with stable ischemic heart disease or ACS who underwent SVG PCI without embolic protection devices from 2010 to 2024 at our center. All received 200 to 400 μg intracoronary adenosine within 30 seconds just prior to each balloon or stent inflation, and post-PCI outcomes were evaluated.
Results
Of 171 patients, 71.2% were mene, and 83% presented with ACS. Pre-PCI Thrombolysis in Myocardial Infarction (TIMI) flow was <3 in 41.1% of the patients. Using the adenosine protocol, no-reflow occurred in 1.2% and slow flow in 4.7%. SNR incidence was 0% in patients with pre-PCI TIMI flow 3 vs higher in those with pre-PCI TIMI <3 (P = .01). Major adverse cardiovascular event rates were 2.3%, 4.6%, and 8.7% at in-hospital, 30-day, and 1-year follow-up, respectively, with significantly better outcomes in the TIMI 3 group (P = .020). Target vessel revascularization was 3.5% at both 30 days and 1 year.
Conclusions
High-dose intracoronary adenosine protocol described in this study markedly reduced the incidence of SNR and was associated with improved short- and long-term outcomes in patients undergoing SVG PCI.
Keywords: adenosine, no-reflow, percutaneous coronary intervention, saphenous vein graft, slow flow
Introduction
Background
Coronary artery disease is the leading cause of mortality globally.1 In patients with complex coronary anatomy, coronary artery bypass grafting (CABG) is the preferred revascularization strategy.2 Saphenous vein grafts (SVG) are currently used in approximately 80% of CABG procedures to bypass the stenosed segment of the coronary artery.3 However, over time, these grafts can degenerate and develop atherosclerosis, leading to recurrent ischemia and the need for repeat revascularization. In such cases, percutaneous coronary intervention (PCI) is favored due to the higher mortality associated with redo CABG.4 Current PCI practices advocate native vessel PCI over graft PCI in post-CABG patients. However, the findings from the PROCTOR (Percutaneous Coronary Intervention of Native Coronary Artery versus Saphenous Vein Graft in Patients with Prior Coronary Artery Bypass Graft Surgery) trial, the largest randomized study comparing native vessel PCI with SVG PCI, demonstrated superior outcomes with SVG PCI.5 Native vessel PCI in post-CABG patients is associated with higher procedural complexity and lower success rates due to heavily calcified vessels, higher incidence of chronic total occlusion (CTO), advanced and expensive equipment utilization, increased fluoroscopy time and radiation exposure, and increased contrast dye use.6, 7, 8, 9, 10 Due to these factors, a significant proportion of interventions are still being done on SVG. As an example, of 20,635 PCI performed at the Oklahoma Heart Hospital, one of the highest volume complex PCI centers in the United States, 7.49% were SVG PCI.
On the other hand, SVG PCI is also considered a high-risk procedure owing to the development of slow or no-reflow (SNR) phenomenon resulting in increased incidence of major adverse cardiovascular events (MACE) up to 10% at 1 month.11 The SNR is characterized by the angiographic evidence of no or reduced antegrade epicardial blood flow in the absence of mechanical obstruction.12
Current knowledge
The literature review reports an incidence of 10% to 15% of SNR in SVG PCI and up to 29% in cases of non–ST-elevation myocardial infarction patients undergoing SVG PCI.13, 14, 15 The 2021 American College of Cardiology/American Heart Association and the 2018 European Society of Cardiology guidelines recommend the use of an embolic protection device (EPD) during SVG PCI when technically feasible to prevent SNR (class IIa).16,17 However, the availability and effectiveness of these devices can vary, and they may not completely eliminate the risk of adverse outcomes.6,18,19 In the instances where an EPD is not feasible or available, the use of intracoronary microvascular vasodilators, including verapamil, adenosine, nitroprusside, or nicardipine, can be useful in the prevention and treatment of no-reflow. However, large-scale studies are still needed to study their beneficial effects in SVG PCI.20
Adenosine, a purine nucleoside with potent vasodilatory properties and a very short half-life, exerts its vasodilatory effects through interaction with specific A2A and A2B receptors in vascular smooth muscle cells. The former plays a significant role in endothelium-independent coronary microvascular vasodilation and is thus not affected by endothelial injury.21 This mechanism can be beneficial in the context of SVG PCI, where high plaque burden and the potential for distal embolization impair microvascular function. By facilitating coronary blood flow and reducing vascular resistance, adenosine can help prevent or alleviate SNR during and after SVG PCI. Only a few studies have studied the role of high-dose intracoronary adenosine during SVG PCI to date. In a randomized study by Kapoor et al,22 only 22 patients with SVG stenoses were randomized to receive either a 10-minute intragraft adenosine infusion (200 g/min; total dose = 2000 g) or normal saline prior to stenting. In the control group, 4 patients (36%) developed no-reflow compared to none in the adenosine-treated patients.22 In another randomized study on 32 patients, 16 patients received 2 times the dose of adenosine (2 mg + 2 mg) to the SVG during PCI, whereas the other 16 received a placebo. No-reflow was observed in 6.25% of the patients in the adenosine group compared to 37.5% in the placebo group. However, an EPD was also used with this protocol.23 Although in the study by Sdringola et al,13 >5 rapid and repeated 24 μg intracoronary adenosine boluses reversed SNR in 91% of the patients as compared to 33% in patients who received <5 boluses.
Gaps in knowledge and rationale of the study
Previous studies have administered adenosine via infusion or repeated boluses over time during the PCI procedure, with some of them using EPD, but the effects of high-dose intracoronary adenosine without the use of an EPD have not been studied before on a large number of patients. At our institution, we implemented a protocol that involved administering 200 to 400 μg of intracoronary adenosine within 30 seconds of each balloon or stent inflation without the use of distal EPD in order to prevent SNR. This approach was chosen due to adenosine's short half-life of <10 seconds and the potential for maximal plaque shift and thrombus disruption during balloon inflation. In this study, we report our experience with this protocol over the last 15 years. Although previous studies were randomized trials with smaller populations, our study has analyzed a large retrospective dataset from a single-center, elaborating on both short- and long-term outcomes in patients who received this protocol. This study highlights the protocol's potential relevance in clinical practice.
Materials and methods
Study design
This is a retrospective analysis of 171 patients who underwent SVG PCI without EPD and utilized the high-dose adenosine protocol from 2010 to 2024 at Oklahoma Heart Hospital. This study included both stable ischemic heart disease (SIHD) and acute coronary syndrome (ACS) patients. Patients with incomplete medical records were excluded from the study. All relevant demographic characteristics, clinical, and angiographic data were collected to complete the analysis.
Outcomes
The primary outcomes were the incidence of SNR assessed by the final Thrombolysis in Myocardial Infarction (TIMI) grade flow at the end of the procedure and MACE. Secondary end points were the safety of the new protocol for intracoronary administration of high-dose adenosine.
Ethics
The research adhered to the highest ethical standards and guidelines established by regulatory bodies. The study protocol was approved by the Western Institutional Review Board (Study Num: 20241003, WO Num: 1-1808973-1).
Treatment protocol
A guide catheter was engaged at the ostium of the diseased SVG, and a coronary wire was advanced across the lesion using standard techniques. EPD was not used. An adenosine bolus was prepared by diluting 3 mg/mL adenosine in 300 mL normal saline, giving a concentration of 10 μg/mL. A manual injection of 200 to 400 μg of adenosine (20 mL of prepared adenosine in a 20 cc syringe) was given as a bolus dose within 30 seconds just prior to each balloon or stent inflation.
Angiographic analysis
Coronary angiograms were assessed individually by experienced interventional cardiologists who were not primary operators. Cine angiograms were recorded at 15 frames/s. The following analyses were performed: TIMI flow grade and myocardial blush grade (MBG) pre- and post-PCI, lesion length, percentage of lesion stenosis, SVG degeneration score, and TIMI clot burden.
Definitions
The TIMI flow grade is defined as follows: TIMI 0 indicates no antegrade flow past the occlusion; TIMI 1 shows that contrast reaches beyond the occlusion but does not perfuse the distal area; TIMI 2 signifies partial reperfusion, where contrast opacifies the distal bed more slowly than in nonoccluded vessels; and TIMI 3 represents complete perfusion, with contrast opacifying the epicardial artery as effectively as in nonoccluded arteries.24 No-reflow is defined as TIMI 0 or 1 flow, whereas slow flow is defined as TIMI 2 flow.
The MACE was defined as a composite end point including death, myocardial infarction (MI), target vessel revascularization (TVR), and stroke after index SVG PCI. Periprocedural MI in patients with SIHD is defined as any 2 of the following: (1) rise in troponin >5 times the upper limit, (2) ECG changes suggestive of ischemia, and (3) anginal chest pain.
Myocardial blush grade is defined as follows: MBG 0 indicates no contrast entry into the microvasculature, often showing staining due to leakage; MBG 1 signifies slow entry with minimal blush; MBG 2 reflects delayed entry and exit compared to the contralateral vessel; and MBG 3 indicates normal entry and exit of contrast from the microvasculature, similar to the contralateral vessel.25
Angiographic thrombus burden was defined as: Grade 0, no thrombus visualized; grade 1, features suggestive of but not firmly diagnostic of thrombus; grade 2, the thrombus’ greatest dimension is less than half of vessel diameter; grade 3, greatest dimension more than half to less than 2 times vessel diameters; grade 4, greatest dimension more than 2 times the vessel diameters; and grade 5, total vessel occlusion due to thrombus.26
The SVG degeneration score is an ordinal scale that measures lumen irregularities and ectasia in SVG. It categorizes degeneration based on the percentage of the total graft length affected: score 0 indicates <25% involvement; score 1 represents 26% to 50%; score 2 corresponds to 51% to 75%; and score 3 reflects over 75% involvement.27
A lesion <10 mm in length was considered as discrete, 10 to 20 mm as tubular, and greater than 20 mm as diffuse. Lesion severity was defined as stenosis >70% as severe, 50% to 70% moderate, and <50% as mild, by taking the diameter of the vessel segment distal to the stenosis as the reference diameter.
Statistical analysis
Statistical analysis was conducted using SPSS version 27 (IBM Corp). Continuous variables are presented as mean ± SD, while categorical variables are summarized as percentage (%) of patients. Comparisons between categorical variables were made using the χ2 test, and Pearson’s correlation test was employed for continuous variables. A P value of <.05 was considered statistically significant. Differences in variables between patient groups were assessed using parametric tests, including the independent samples t test and 1-way ANOVA. Logistic regression was performed to assess the association between variables and the likelihood of specific outcomes, accounting for potential confounders.
Results
Patient demographics and baseline characteristics
A total of 171 patients were included in the study, with 123 (71.9%) men and 48 (28.1%) women. Among them, 142 (83.04%) presented with ACS, whereas 29 (16.95%) had SIHD. Diabetes mellitus type 2 was present in 84 (49.1%), chronic kidney disease in 44 (25.7%), hypertension in 160 (93.6%), hyperlipidemia in 167 (97.7%), and smoking history in 99 (57.9%) patients. Forty-one (24%) patients were on aspirin monotherapy, and 112 (65.5%) were on dual antiplatelet therapy before PCI (for details, see Table 1).
Table 1.
Patient demographics and baseline and lesion characteristics.
| Characteristic | N = 171 |
|---|---|
| Sex | |
| Male | 123 (71.9%) |
| Female | 48 (28.1%) |
| Race/ethnicity | |
| American Indian/Alaska Native | 2 (1.2%) |
| Asian | 4 (2.3%) |
| Black or African American | 4 (2.3%) |
| Caucasian/White | 158 (92.4%) |
| Hispanic/Latino | 3 (1.8%) |
| Comorbidities | |
| Type 2 diabetes mellitus | 84 (49.1%) |
| Chronic kidney disease | 44 (25.7%) |
| Hypertension | 160 (93.6%) |
| Hyperlipidemia | 167 (97.7%) |
| Smoking | 99 (57.9%) |
| Prior PCI to the vein graft | 72 (42.1%) |
| Restenosis | 31 (18.1%) |
| Antiplatelet preprocedure | |
| Aspirin monotherapy | 41 (24%) |
| Dual antiplatelet therapy | 112 (65.5%) |
| All other interventions | 18 (10.5%) |
| Admission diagnosis | |
| Acute coronary syndromes | 142 (83%) |
| Stable angina | 29 (17%) |
| TIMI flow grade pre-PCI | |
| <3 | 74 (43.3%) |
| 3 | 97 (56.7%) |
| MBG pre-PCI | |
| 0 | 13 (7.6%) |
| 1 | 34 (19.9%) |
| 2 | 102 (59.6%) |
| 3 | 22 (12.9%) |
| SVG degeneration score | |
| 0 | 1 (0.6%) |
| 1 | 98 (57.3%) |
| 2 | 49 (28.7%) |
| 3 | 19 (11.1%) |
| 4 | 4 (2.3%) |
| TIMI clot burden pre-PCI | |
| 0 | 2 (1.2%) |
| 1 | 85 (49.7%) |
| 2 | 57 (33.3%) |
| 3 | 19 (11.1%) |
| 4 | 8 (4.7%) |
| No. of lesions | |
| 0 | 1 (0.6%) |
| 1 | 133 (77.8%) |
| 2 | 31 (18.1%) |
| 3 | 4 (2.3 %) |
| No. of stents | |
| 0 | 19 (11.1%) |
| 1 | 131 (76.6%) |
| 2 | 19 (11.1%) |
| 3 | 2 (1.2%) |
Values are n (%). MBG, myocardial blush grade; PCI, percutaneous coronary intervention; SVG, saphenous vein graft; TIMI, Thrombolysis in Myocardial Infarction.
Lesion characteristics
Preprocedural TIMI flow grade 3 was observed in 97 patients (58.9%), whereas 74 patients (41.1%) had TIMI flow <3. MBG <3 was found in 149 patients (87.1%), with only 22 patients (12.9%) exhibiting MBG grade 3. Additionally, 76 patients had TIMI 3 flow but MBG <3 pre-PCI. The SVG degeneration score was ≤2 in 148 patients (86.5%) and >2 in 23 patients (13.5%). TIMI clot burden scores were ≤2 in 144 patients (84.2%) and >2 in 27 patients (15.8%) (for details, refer to Table 1).
Clinical outcomes
Postprocedural SNR was rare in this study of the largest patient number to date using adenosine protocol, with only 2 patients (1.2%) experiencing no-reflow, and 8 patients (4.67%) experiencing slow flow (Figure 1, Table 2). None of the patients with preprocedural TIMI grade 3 flow, MBG grade 3, or TIMI clot burden <2 developed SNR (Figure 2, Table 3). However, patients with TIMI flow <3, MBG <3, or SVG degeneration score >2 showed a higher incidence of SNR, with statistically significant associations observed between preprocedural TIMI flow (χ2 = 13.922, P = .001), TIMI clot burden (χ2 = 14.049, P = .001), and post-PCI outcomes (Tables 4 and 5).
Figure 1.
Postprocedural slow or no-reflow (SNR) in the included population.
Table 2.
Clinical outcomes.
| Outcome | N = 171 |
|---|---|
| Periprocedural myocardial infarction | 4 (2.3%) |
| Major adverse cardiovascular events | |
| In-hospital | 4 (2.3%) |
| 30 Days | 8 (4.7%) |
| 1 Year | 15 (8.8%) |
| Target vessel revascularization | |
| 30 Days | 6 (3.5%) |
| 1 Year | 6 (3.5%) |
| Persistent ST-segment elevation | 3 (1.8%) |
| Bradyarrhythmia postadenosine | 5 (2.9%) |
| Tachyarrhythmia postadenosine | 2 (1.2%) |
| TIMI post-PCI | |
| No-reflow | 2 (1.2) |
| Normal reflow | 161 (94.2) |
| Slow reflow | 8 (4.7) |
Values are n (%). PCI, percutaneous coronary intervention; TIMI, Thrombolysis in Myocardial Infarction.
Figure 2.
The incidence of slow or no-reflow in patients with stable ischemic heart disease (SIHD) and acute coronary syndrome (ACS). PCI, percutaneous coronary intervention; TIMI, Thrombolysis in Myocardial Infarction.
Table 3.
Correlation between pre-PCI lesion characteristics and post-PCI TIMI flow.
| Lesion characteristics pre-PCI | Post-PCI TIMI flow |
P value | ||
|---|---|---|---|---|
| No-reflow | Slow flow | Normal flow | ||
| TIMI flow <3 | 2 (2.7%) | 8 (10.8%) | 64 (86.5%) | .001 |
| TIMI flow 3 | 0 (0%) | 0 (0%) | 97 (100%) | |
| MBG <3 | 2 (1.3%) | 8 (5.4%) | 139 (93.3%) | .457 |
| MBG 3 | 0 (0%) | 0 (0%) | 22 (100%) | |
| SVG degeneration score >2 | 1 (4.3%) | 2 (8.7%) | 20 (87.0%) | .187 |
| SVG degeneration score ≤2 | 1 (0.7%) | 141 (95.3%) | 6 (4.1%) | |
| TIMI clot burden >2 | 2 (7.4%) | 3 (11.1%) | 22 (81.5%) | .001 |
| TIMI clot burden ≤2 | 0 (0%) | 5 (3.5%) | 139 (96.5%) | |
MBG, myocardial blush grade; PCI, percutaneous coronary intervention; SVG, saphenous vein graft; TIMI, Thrombolysis in Myocardial Infarction.
Table 4.
Outcomes in patients by pre-PCI TIMI flow.
| Outcome | Pre-PCI TIMI flow |
P value | |
|---|---|---|---|
| TIMI <3 (n = 74) | TIMI 3 (n = 97) | ||
| Periprocedural MI | 2 (2.7%) | 2 (2.1%) | .784 |
| Major adverse cardiovascular events | |||
| In hospital | 4 (5.4%) | 0 (0.0%) | .020 |
| 30-Days | 2 (2.7%) | 6 (6.2%) | .294 |
| 1 Year | 5 (6.8%) | 10 (10.3%) | .209 |
| Target vessel revascularization | |||
| 30 Days | 3 (4.1%) | 3 (3.1%) | .735 |
| 1 Year | 1 (1.4%) | 5 (5.2%) | .391 |
MI, myocardial infarction; PCI, percutaneous coronary intervention; TIMI, Thrombolysis in Myocardial Infarction.
Table 5.
Outcomes in patients by pre-PCI myocardial blush grade.
| Outcome | Pre-PCI MBG |
P value | |
|---|---|---|---|
| MBG <3 (n = 149) | MBG 3 (n = 22) | ||
| Periprocedural MI | 3 (2.0%) | 1 (4.5%) | .463 |
| Major adverse cardiovascular events | |||
| In-hospital | 4 (2.7%) | 0 (0.0%) | .437 |
| 30 Days | 5 (3.4%) | 3 (13.6%) | .091 |
| 1 Year | 12 (8.1%) | 3 (13.6%) | .562 |
MACE, major adverse cardiovascular event; MBG, myocardial blush grade; MI, myocardial infarction; PCI, percutaneous coronary intervention.
Among patients with SIHD, none developed SNR post-PCI, whereas all 10 patients who developed SNR had presented with ACS, suggesting a clinical trend of higher incidence of SNR in ACS patients, although this was not a statistically significant association (χ2 = 2.169, P = .338) (for details, see Figure 3, Table 6).
Figure 3.
The incidence of slow or no-reflow (SNR) based on preprocedural Thrombolysis in Myocardial Infarction (TIMI) flow of the patients.
Table 6.
Outcomes by clinical presentation.
| Outcome | ACS (n = 142) | SIHD (n = 29) | P value |
|---|---|---|---|
| Periprocedural MI | 4 (2.8%) | 0 (0.0%) | .360 |
| Major adverse cardiovascular events | |||
| In-hospital | 3 (2.1%) | 1 (3.4%) | .665 |
| 30 Days | 8 (5.6%) | 0 (0.0%) | .080 |
| 1 Year | 15 (10.6%) | 0 (0.0%) | .171 |
ACS, acute coronary syndromes; MI, myocardial infarction; SIHD, stable ischemic heart disease.
Patients with preprocedural TIMI 3 flow, MBG 3, or SVG degeneration score <2 were less likely to experience periprocedural MI compared to those with TIMI <3, MBG <3, or SVG degeneration score >2, with a statistically significant difference for TIMI flow (χ2= 5.369, P = .020). This suggests that better preprocedural coronary perfusion, lower SVG degeneration, and reduced clot burden contribute to more favorable outcomes during SVG PCI (Tables 4 and 5).
The overall in-hospital MACE, 30-day MACE, and 1-year MACE rates were 2.3%, 4.6%, and 8.7%, respectively, with a significant difference between patients with pre-PCI TIMI 3 flow or MBG 3 than those with TIMI flow <3 or MBG < 3 (χ2 = 5.369, P = .020 for TIMI; nonsignificant for MBG). The TVR rate at 30 days was 0% and at 1 year was 3.5% (Tables 2, 4, and 5).
Procedural complications, such as arrhythmias or significant hypotension, were rare and evenly distributed across both groups (Tables 2, 4, and 5). Multinomial and binomial regression analyses did not identify any covariates significantly associated with post-PCI TIMI scores, periprocedural MI, or in-hospital MACE.
Discussion
This single-center, 15-year retrospective study analyzed outcomes in 171 patients who underwent SVG PCI utilizing high-dose intracoronary adenosine within 30 seconds of each balloon or stent inflation without the use of an EPD in ACS and stable angina patients. To the best of our knowledge, this is the largest study investigating the effect of intracoronary adenosine in SVG PCI patients. The findings provide significant insights into the role of this high-dose intracoronary adenosine protocol (Central Illustration).
Central Illustration.
Outcomes of high-dose intracoronary adenosine protocol in SVG PCI. ACS, acute coronary syndrome; MACE, major adverse cardiovascular event; PCI, percutaneous coronary intervention; SIHD, stable ischemic heart disease; SVG, saphenous vein graft; TVR, target vessel revascularization.
Incidence of SNR phenomenon using high-dose intracoronary adenosine protocol
The most remarkable finding from our study is that 0% incidence of SNR was observed in patients with pre-PCI TIMI flow 3. In patients with pre-PCI TIMI flow <3, no-reflow was observed in only 1.2% of the patients, whereas slow flow was seen in only 4.3% of the patients. This incidence was only observed in patients presenting with ACS and pre-PCI TIMI flow <3. The majority of patients in our study (83.04%) presented with ACS, and 41% of them had pre-PCI TIMI flow <3. These findings suggest a dramatic reduction in SNR that has been reported to have a high incidence of 10% to 15% in patients undergoing SVG PCI in previous studies, with other studies suggesting an incidence of 29% in patients with non–ST elevation MI undergoing SVG PCI.13, 14, 15 The reference literature rates were derived from studies that included patients undergoing SVG PCI both with and without the use of EPD. For instance, in the study by Sdringola et al,14 SVG PCI was performed without EPD use, and included patients with both ACS and stable coronary artery disease, as in our study, and reported a SNR incidence of 14.1%. In contrast, Gürbak et al,15 focused exclusively on ACS patients, where EPD were used in 5.1% of cases and reported a higher SNR rate (29%). Moreover, the definitions used to derive SNR were similar in these studies. The incidence of SNR in our study is even lower than the incidence of SNR in ACS patients undergoing native vessel PCI, which is reported to be 5% to 25%.28 The difference likely reflects both the protective effect of the proposed adenosine protocol and the consistency in procedural technique. SNR in our study was adjudicated using standard angiographic criteria, ensuring comparability with the methods used in the cited literature. Although methodological and population differences may influence reported rates, the dramatic reduction observed in our study highlights the potential clinical benefit of high-dose adenosine in preventing SNR during SVG PCI. Furthermore, pre-PCI TIMI flow is a major determinant of post-PCI TIMI flow and MACE in our study, which is in accordance with a previous study’s results.29
Slow or no-reflow is often attributed to a combination of factors, including microvascular dysfunction, inflammatory response, and distal embolization during intervention. The highest level of microembolization during SVG PCI typically occurs during balloon inflation. This phase can disrupt plaque and thrombus, potentially releasing microemboli into the bloodstream, which may contribute to the SNR and impact myocardial perfusion. By providing a high concentration of adenosine within 30 seconds of each balloon inflation, we may facilitate the opening of constricted microvessels, enhance coronary flow reserve, and improve myocardial perfusion. The observed dramatic reduction in no-reflow rates in this study reinforces the notion that high-dose adenosine, particularly given before each balloon or stent inflation, can effectively counteract these adverse events, allowing for better restoration of blood flow and oxygen delivery to the myocardium.
Short- and long-term outcomes
The reduction in MACE associated with the use of high-dose adenosine represents a pivotal finding. MACE constitutes a major concern in patients undergoing SVG PCI. In our study, the incidence of in-hospital, 30-day, and 1-year MACE is 2.3%, 4.6%, and 8.7%, respectively, and is lower in patients with pre-PCI TIMI flow 3 and stable angina presentation. The overall incidence of MACE is noticeably less compared to other studies, which have reported an incidence of 10% at 30 days10; in patients with ACS undergoing SVG PCI, it is reported to be up to 15% at 30 days and 31% at 1 year.30 In our study, the TVR at 30 days and 1 year was 3.5%. A review of literature reveals higher TVR in patients undergoing SVG PCI and is reported to be 10.3% at 1 year.30 The ability of high-dose adenosine to reduce these events suggests that this protocol provides a clinically safe and effective management strategy for SVG interventions.
Safety of high-dose intracoronary adenosine protocol
Furthermore, it is thought that administration of high-dose adenosine might result in significant bradyarrhythmias or hypotension, but doses as high as 3600 μg were well tolerated, and no clinically significant incidence of bradyarrhythmias or hypotension was noted in our study. This further signifies the safety of using this protocol in clinical practice.
The current PCI practices recommend native coronary artery intervention in post-CABG patients with significant SVG stenoses preferentially over SVG PCI because the former was thought to provide better long-term patency. However, with the findings from the PROCTOR trial, SVG PCI has now shown superior outcomes as compared to native vessel PCI.5 Native vessel PCI in post-CABG patients is often more complex and requires a higher level of expertise to deal with heavily calcified lesions. There is also a high incidence of native vessel CTO in over 50% of post-CABG patient population, and often with higher JCTO scores.6,8,9 A larger number of advanced devices, like the rotablator system, microcatheters, and guide-extension devices, are employed to navigate these lesions.8 These lesions are associated with a lower success rate as compared to nongrafted vessels. The success of these complex interventions is also heavily influenced by the operator's experience and the annual volume of CTO-PCI procedures performed at a center, with <10% of operators falling into the highest experience tertile.8,10 Moreover, the routine use of EPD in SVG PCI has not been proven to lower all-cause mortality or cardiovascular events.18 They are also not commonly available, particularly in low middle income countries, where this protocol can potentially improve outcomes. An analysis from the American College of Cardiology–NCDR indicated that EPD were used in 22% of SVG PCI, whereas a more recent study noted their usage in 28% of cases only.6,19
The ease of administration and rapid onset of action associated with adenosine make it an attractive option for clinicians. As health care systems increasingly seek cost effective and efficient interventions, the high-dose adenosine protocol emerges as a viable approach that can enhance patient care while potentially reducing hospital resource utilization. This study provides promising results supporting the use of high-dose intracoronary adenosine before each balloon or stent inflation in patients undergoing SVG PCI, signifying its effectiveness in this complex and high-risk patient population.
Limitations and future prospects
Because this is a retrospective single-center study with a small sample size, it carries some inherent limitations, and although the results are promising, they will need to be further validated with large randomized trials. Our study has a much higher percentage of men (71.9%) and, therefore, its generalizability to women who, in general, have a higher incidence of MACE may be limited. Furthermore, although the study results suggest high efficacy of this protocol across both ACS and SIHD patients, the latter cohort is very small (16.9%), and therefore, efficacy for this patient group will need to be interpreted with caution. The exclusion of patients with incomplete records and follow-up can also affect the results of the study, which is an inherent limitation of the retrospective design.
Despite these limitations, we believe that ours is the study with the largest patient volume investigating the efficacy and safety of the adenosine protocol in SVG PCI and offers very promising results that can inform further randomized trials and future clinical practice.
Conclusion
In conclusion, the use of the high-dose adenosine protocol resulted in significantly lower incidence of SNR and MACE in patients undergoing SVG PCI. Its potential to prevent SNR and improve patient outcomes positions it as a promising strategy in the management of patients with ACS or stable angina undergoing SVG PCI.
Acknowledgments
Declaration of competing interest
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding sources
This work was not supported by funding agencies in the public, commercial, or not-for-profit sectors.
Ethics statement and patient consent
This ethics statement affirms that the research adhered to the highest ethical standards and guidelines established by regulatory bodies (Western Institutional Review Board, Study Num: 20241003, WO Num: 1-1808973-1). The confidentiality and privacy of participant information were maintained, conflicts of interest were denied, high morals were upheld, data integrity and transparency were ensured, authorship criteria were outlined, and contributions were acknowledged appropriately.
Data availability statement
The data that support the findings of this study are available (upon request/from the corresponding author). Restrictions apply to the availability of these data, which were used under license for the current study and are not publicly available. However, the data are available from the authors upon reasonable request and with permission from Oklahoma Heart Hospital. Any additional data related to this study will be made available in accordance with journal policies and upon request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available (upon request/from the corresponding author). Restrictions apply to the availability of these data, which were used under license for the current study and are not publicly available. However, the data are available from the authors upon reasonable request and with permission from Oklahoma Heart Hospital. Any additional data related to this study will be made available in accordance with journal policies and upon request.