Tabla 1. Baseline characteristics of the sample population.

Tabla 2. Anatomical characteristics and features of the percutaneous revascularization procedure..

Figura 1. Distribution of anatomical complexity and residual coronary disease according to baseline ...

Figura 2. Cumulative incidence of NACE according to residual atherosclerotic coronary disease by rSS...

Introduction

In a setting of ST-segment elevation acute myocardial infarction (STEMI), multivessel disease (MVD) is a common condition associated with an increased risk of recurrent ischemia, hemorrhagic events, and high mortality during follow-up1 Moreover, the impact of MVD on adverse clinical events in STEMI may vary according to the complexity and severity of the evidenced atherosclerotic coronary disease.

The SYNTAX score (SYNergy between PCI with TAXus and cardiac surgery [SS]) is a validated tool used to quantify and systematically characterize, through angiographic visual analysis, the severity and complexity of coronary disease. It is closely associated with adverse clinical events in the short-, medium-, and long-term follow-up2-5. Additionally, the residual SYNTAX score (rSS), a tool to characterize the burden of residual atherosclerotic coronary disease after percutaneous transluminal coronary intervention (PCI), has been linked to adverse clinical events during follow-up, both in the setting of acute coronary syndromes with and without ST-segment elevation, respectively6, 7.

To date, there is limited evidence regarding the prognostic role and impact of rSS on adverse clinical events during follow-up in STEMI, as well as potential predictors of high rSS.

Materials and methods

We conducted a single-center, retrospective observational study, which included consecutive patients diagnosed with STEMI who underwent PCI at a high-complexity, multi-specialty medical center between January 2020 and October 2023. Baseline characteristics, administered antithrombotic medical treatment, data from the index revascularization procedure, biochemical factors, and adverse clinical events during follow-up were analyzed for the entire cohort, with a follow-up period of two years from the index coronary event. We identified the baseline SYNTAX score (bSS, determined using online calculator www.syntaxscore.com, version 2.1), the residual SYNTAX score (rSS) after PCI, and the difference between both scores (ΔSYNTAX) as a surrogate for the burden of coronary atherosclerotic disease treated with PCI.

The entire cohort was stratified according to the presence or absence of MVD, completion or incompletion of revascularization after the index procedure, and burden of residual coronary disease according to rSS into low rSS (0 points), intermediate rSS (1-8 points), and high rSS (>8 points), respectively. In cases with subsequent percutaneous transluminal coronary angioplasty (PTCA) during the index hospitalization, the rSS was determined after the first invasive procedure. Patients with STEMI treated with conservative medical treatment, anti-thrombotic agents or myocardial revascularization surgery, pharmacoinvasive reperfusion strategy, and facilitated coronary angioplasty were excluded.

The primary endpoint was the clinical impact of post-PCI residual coronary atherosclerotic disease as determined by rSS, in terms of a composite of in-hospital death, recurrent acute myocardial infarction (AMI), need for unplanned new myocardial revascularization, and bleeding events (net adverse clinical event [NACE]) with a follow-up period of 2 years from the index coronary event. The secondary endpoint was the analysis of clinical and anatomical predictors of high rSS.

Definitions

• Baseline SYNTAX score (bSS). Reproducible quantitative measure of the complexity and severity of coronary disease, with the following parameters: SS=0-21, “low anatomical complexity”; SS=22-32, “intermediate anatomical complexity”; SS ≥33, “high anatomical complexity”2.

• Residual SYNTAX score (rSS). Reproducible quantitative measure of the complexity and severity of post-PCI residual coronary disease, classified as follows: rSS=0, “complete revascularization”; rSS=1-8, “incomplete revascularization with low residual coronary disease burden”; rSS >8, “incomplete revascularization with high residual coronary disease burden”7.

• Coronary flow grade. Parameter determined using the TIMI (Thrombolysis in Myocardial Infarction) flow classification: TIMI=0, “total occlusion with no antegrade perfusion”; TIMI=1, “penetration beyond the coronary obstruction site with no distal vascular bed perfusion”; TIMI=2, “partial distal perfusion with antegrade flow and slow contrast clearing”; TIMI=3, “complete perfusion with antegrade flow and rapid contrast clearing”8.

• Culprit vessel of the index coronary event. The coronary vessel with angiographic evidence of total or subtotal thrombotic luminal occlusion and topographical correlation with electrocardiographic ST-segment elevation.

• Bleeding. Bleeding severity was classified according to the BARC (Bleeding Academic Research Consortium) scale. Bleeding episodes had to be BARC ≥3 to be considered for this study9.

Statistical analysis

Continuous variables were expressed as mean and standard deviation or median and interquartile range, depending on their distribution characteristics. The Kolmogorov-Smirnov or Shapiro-Wilk tests were used to assess normality, as appropriate. Categorical variables were expressed as frequency and percentage, and they were analyzed using the Chi-square test or Fisher’s exact test. Numerical variables were compared using Student’s t-test or Mann-Whitney U test, depending on their distribution. A multivariate binary logistic regression model was used to analyze the relevant variables in order to identify predictors of high rSS, as well as independent risk factors for NACE during follow-up. A survival analysis was conducted using the Log-Rank test and expressed with the Kaplan-Meier estimator for adverse clinical events during follow-up according to the burden of residual coronary disease after PCI, as stratified by rSS. Statistical significance was considered as a type I error rate less than or equal to 5% (p < 0.05, two-sided). Statistical analysis was performed using SPSS version 29 (IBM SPSS Statistics, IBM Corporation, Armonk, NY).

Results

A total of 228 patients were included for analysis. Cohort characteristics included in this analysis are detailed in Table 1. The average age of the sample population was 67.77±13.29 years, and there was a predominance of men (70.7%). The average baseline SS and rSS scores were 14.0±9.40 and 7.22±7.91, respectively. Additionally, the average ΔSYNTAX score (accounting for the burden of disease eliminated by PCI) was 5.17±5.15 points. Considering the total cohort included in the analysis, 14.0% of subjects underwent complete revascularization, 51.4% had incomplete revascularization with a low burden of residual coronary disease, and 34.6% had incomplete revascularization with a high burden of residual coronary disease after PCI. Furthermore, in terms of baseline anatomical complexity measured by the bSS, there was a growing trend towards higher baseline complexity correlating with greater residual coronary disease burden after PCI (Figure 1).

The subgroup of patients with high rSS was older and had a higher burden of comorbidities, such as hypertension, diabetes mellitus, and peripheral vascular disease, compared to those with intermediate or low rSS. The reasons for not achieving complete revascularization (rSS=0) included procedural failure in 12.3% of cases or a decision by the medical team not to revascularize lesions with certain characteristics at the time of the index procedure (diffuse distal bed involvement, chronic total occlusions).

Regarding anatomical parameters and aspects related to the revascularization procedure, most patients were in Killip and Kimball stage I at the time of clinical presentation (83.8%). The transradial access (86.4%) was the most common vascular access. The most frequent culprit vessel of the index coronary event was the circumflex artery (36.8%), followed by the left anterior descending artery, and the right coronary artery, respectively. After culprit vessel PCI, complete restoration of antegrade coronary flow was achieved in most cases (78.9%) (Table 2).

In terms of the primary endpoint, the subgroup of patients with high rSS had a higher occurrence of NACE during follow-up compared to those with intermediate (rSS >8 11.3% vs. rSS 1-8 4.6%) or low rSS (rSS >8 11.3% vs. rSS 0 3.1%; Log-Rank test p=0.006). There was a statistically significant difference between the subgroups analyzed (Figure 2).

These findings were driven by a higher occurrence of recurrent MI (4.7% vs. 1.3%; p=0.03) and a greater need for unplanned revascularization during follow-up (3.9% vs. 1.1%; p=0.04) in patients with high rSS compared to those with a non-high rSS, respectively. On the other hand, there were no statistically significant differences in terms of in-hospital death and bleeding events between the study subgroups.

Using multivariate binary logistic regression analysis, the presence of high rSS was identified as an independent predictor of NACE during follow-up (OR 1.25 [95% CI 1.11-1.60]; p=0.03). Furthermore, the independent predictors of high rSS included a history of diabetes mellitus (odds ratio [OR] 2.4 [95% confidence interval (CI) 1.33-5.70]; p=0.04), coronary artery disease with 2-vessel involvement (2-V) (OR 8.40 [95% CI 6.20-9.54]; p=0.03 vs. 1-V), and coronary artery disease with 3-vessel involvement (3-V) (OR 28.10 [95% CI 13.59-32.10]; p=0.04 vs. 1-V).

Discussion

Based on the results of this study, we can highlight the findings below. First, in patients with STEMI undergoing revascularization via PCI, there was a notable prevalence of incomplete revascularization. Second, incomplete revascularization after PCI was associated with higher rates of adverse clinical events during follow-up. Third, incomplete revascularization, as measured by rSS, was identified as an independent predictor of worse clinical outcomes. Fourth, predictors of higher rSS after PCI included diabetes mellitus and coronary atherosclerotic disease with 2- and 3-vessel involvement.

MVD is a frequently observed clinical entity in patients with STEMI, particularly in older populations10, 11. It has been previously shown that the presence of concomitant MVD is associated with a higher incidence of recurrent ischemic events after STEMI, most likely linked to the instability of secondary atherosclerotic plaque, impaired myocardial perfusion, and altered contractility in non-infarcted areas12. This is valuable information, considering that several studies have suggested that atherosclerotic plaque rupture in a non-culprit vessel of the index event is a significantly prevalent event, estimated at 25%13. Clinical management guidelines recommend complete revascularization based on its benefit in reducing adverse clinical events during follow-up.

This study demonstrated that more than half of the STEMI patients undergoing PCI had MVD and incomplete revascularization, as measured by the rSS, which was consistent with findings in the literature14. Furthermore, the subgroup of patients with high rSS in our cohort had worse clinical outcomes during follow-up, which is in line with previous studies. In this context, a retrospective observational study that included 518 STEMI patients undergoing PCI showed that patients with incomplete revascularization had a higher incidence of all-cause mortality compared to those with complete revascularization (24% vs. 12%; p < 0.001), even after excluding from the analysis the first 30 days after the index coronary event. It is worth noting that, unlike in the aforementioned study, incomplete revascularization in our cohort was not an independent risk factor for mortality during follow-up15.

It has been shown that the extent of incomplete revascularization after PCI plays a prognostic role during follow-up. A retrospective study (n=1499) of STEMI patients undergoing PCI in a “real-world” setting demonstrated that in-hospital mortality is lower in the complete revascularization and the mildly incomplete revascularization subgroups compared to the marked incomplete revascularization subgroup, with a statistically significant difference between the subgroups (1.5% vs. 1.7% vs. 9.0%; p < 0.001)16. To date, the COMPLETE study (Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI) is the randomized study with the largest sample size. It identified complete revascularization as the most beneficial strategy in terms of reducing adverse clinical events during follow-up, compared to incomplete revascularization in STEMI17. Thus, complete revascularization, even when staged and not performed during the index procedure, has been identified as associated with a 26-% reduction in the composite clinical outcome of cardiovascular death or recurrent MI at 3 years, compared to culprit-vessel only PCI revascularization, mainly driven by a 32-% reduction in the risk of nonfatal recurrent MI in the complete revascularization subgroup17.

Our study has identified incomplete revascularization, measured by rSS, as an independent risk factor for adverse clinical events during follow-up, a finding consistent with previous studies. For example, a single-center observational prospective study of STEMI patients (n=589) identified rSS as an independent risk factor for the composite clinical outcome of cardiovascular death and MI. The association was stronger with greater incomplete revascularization burden after PCI (hazard ratio [HR] 5.05 [95% CI 2.89-12.00], rSS >8 vs. rSS=0; p < 0.001 and HR 2.96 [95% CI 1.31-6.69], rSS=1-8 vs. rSS=0; p=0.009, respectively)18. In line with these findings, a study identified rSS as a predictor of adverse clinical events during follow-up, with an area under the ROC curve of 0.92 for survival discrimination19.

Since incomplete revascularization has shown a detrimental clinical effect during follow-up in patients with STEMI, identifying its predictors is essential for the identification of the higher-risk patient subgroup. In this context, our study identified the presence of diabetes mellitus and 2- or 3-vessel coronary disease as independent predictors of incomplete revascularization after PCI of the culprit vessel, a finding likely linked to anatomical complexity and comparable with what has been found in studies with similar populations. For instance, a pre-specified sub-analysis of the SYNTAX study cohort identified the presence of hyperlipidemia (OR 1.59 [95% CI 1.04-2.42; p=0.031]), chronic total occlusion (OR 2.46 [95% CI 1.66-3.64; p< 0.001]), and number of coronary vessels involved (OR 1.58 [95% CI 1.41-1.77; p< 0.001]) as independent factors for incomplete revascularization20.

Limitations

The methodological design of the current study warrants mentioning certain relevant limitations. First, while the data come from a cohort with substantial sample size, the study is observational and lacks randomization between the compared groups, introducing the possibility of unidentified confounding factors that may not be fully addressed through Cox regression analysis. Second, the cut-off points implemented in this study to determine the amount of residual coronary disease after PCI by means of rSS have been used in various studies; however, it is worth noting that there are other variants, so the obtained data should be considered cautiously. Finally, the sample population included for this analysis is a younger population (< 75 years) with low anatomical complexity according to the bSS score, so the observed findings should not be extrapolated to older populations with higher bSS scores. For the aforementioned reasons, future studies of “real world” patients in our setting are needed to draw robust conclusions.

Conclusions

In a clinical scenario of STEMI, residual coronary disease following culprit-vessel PCI revascularization, as measured by rSS, carries prognostic value in terms of the occurrence of adverse clinical events during follow-up. The concomitant presence of diabetes mellitus and multivessel coronary involvement were identified as independent predictors of high rSS.

Summary of key points

• Multivessel disease in STEMI patients is associated with a higher risk of adverse clinical events.

• The SYNTAX score is an effective tool to assess coronary complexity and guide revascularization strategy.

• The burden of residual atherosclerotic disease, measured through the residual SYNTAX score (rSS), has prognostic value, even though it has not been thoroughly analyzed in our setting.

• This study confirms that high rSS correlates with a higher incidence of adverse clinical events.

• The main predictors of high rSS are diabetes mellitus and multivessel coronary involvement.

1. Park D-W, Clare RM, Schulte PJ, et al. Extent, location, and clinical significance of non-infarct-related coronary artery disease among patients with ST-elevation myocardial infarction. JAMA 2014;312(19):2019–27.

2. Sianos G, Morel M-A, Kappetein AP, et al. The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention 2005;1(2):219–27.

3. Serruys PW, Morice M-C, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 2009;360(10):961–72.

4. ClinicalKey [Internet]. [cited 2024 Jul 31];Available from: https://doi.org/10.1016/S0140-6736(13)60141-5

5. Thuijs DJFM, Kappetein AP, Serruys PW, et al. Percutaneous coronary intervention versus coronary artery bypass grafting in patients with three-vessel or left main coronary artery disease: 10-year follow-up of the multicentre randomised controlled SYNTAX trial. Lancet 2019;394(10206):1325–34.

6. Residual SYNTAX score can predict short- and long-term outcomes in patients with STEMI. Cor Vasa 2018;60(4):e345–51.

7. Généreux P, Palmerini T, Caixeta A, et al. Quantification and impact of untreated coronary artery disease after percutaneous coronary intervention: the residual SYNTAX (Synergy Between PCI with Taxus and Cardiac Surgery) score. J Am Coll Cardiol 2012;59(24):2165–74.

8. TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. N Engl J Med 1985;312(14):932–6.

9. Mehran R, Rao SV, Bhatt DL, et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011;123(23):2736–47.

10. Morici N, Alicandro G, Ferri LA, et al. Residual SYNTAX Score and One-Year Outcome in Elderly Patients With Acute Coronary Syndrome. CJC Open 2020;2(4):236–43.

11. Sorajja P, Gersh BJ, Cox DA, et al. Impact of multivessel disease on reperfusion success and clinical outcomes in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction. Eur Heart J 2007;28(14):1709–16.

12. Bates ER, Tamis-Holland JE, Bittl JA, O’Gara PT, Levine GN. PCI Strategies in Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Coronary Artery Disease. J Am Coll Cardiol 2016;68(10):1066–81.

13. Kubo T, Imanishi T, Kashiwagi M, et al. Multiple coronary lesion instability in patients with acute myocardial infarction as determined by optical coherence tomography. Am J Cardiol 2010;105(3):318–22.

14. Bainey KR, Alemayehu W, Armstrong PW, Westerhout CM, Kaul P, Welsh RC. Long-Term Outcomes of Complete Revascularization With Percutaneous Coronary Intervention in Acute Coronary Syndromes. JACC Cardiovasc Interv 2020;13(13):1557–67.

15. Dimitriu-Leen AC, Hermans MPJ, Veltman CE, et al. Prognosis of complete versus incomplete revascularisation of patients with STEMI with multivessel coronary artery disease: an observational study. Open Heart 2017;4(1):e000541.

16. Braga CG, Cid-Alvarez AB, Diéguez AR, et al. Prognostic impact of residual SYNTAX score in patients with ST-elevation myocardial infarction and multivessel disease: Analysis of an 8-year all-comers registry. Int J Cardiol 2017;243:21–6.

17. Mehta SR, Wood DA, Storey RF, et al. Complete Revascularization with Multivessel PCI for Myocardial Infarction. N Engl J Med 2019;381(15):1411–21.

18. Burgess SN, French JK, Nguyen TL, et al. The impact of incomplete revascularization on early and late outcomes in ST-elevation myocardial infarction. Am Heart J 2018;205:31–41.

19. Malkin CJ, George V, Ghobrial MSA, et al. Residual SYNTAX score after PCI for triple vessel coronary artery disease: quantifying the adverse effect of incomplete revascularisation. EuroIntervention 2013;8(11):1286–95.

20. Head SJ, Mack MJ, Holmes DR Jr, et al. Incidence, predictors and outcomes of incomplete revascularization after percutaneous coronary intervention and coronary artery bypass grafting: a subgroup analysis of 3-year SYNTAX data. Eur J Cardiothorac Surg 2012;41(3):535–41.

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