Non-infarct Related Artery Research Articles

Functional improvement of non-infarct related coronary artery stenosis by extensive LDL-C reduction with a PCSK9 antibody: the FITTER trial, microvascular function analysis

Abstract Background Atherosclerosis and microvascular dysfunction are closely linked. Moreover, impaired microvascular function is strongly associated with increased risk on major adverse cardiac events. In patients presenting with acute coronary syndrome (ACS), microvascular function is reduced. PCSK9-inhibitors have shown to reduce plaque burden and lipid load in epicardial vessels and might exhibit similar results on microvascular vessels, thereby improving microvascular function. The FITTER trial offers the unique opportunity to test this hypothesis. Methods The FITTER trial is a multi-center, randomized, double blind, placebo controlled clinical trial for patients presenting with ACS and multi-vessel disease (MVD). After treatment of the culprit lesion, fractional flow reserve (FFR) measurement of non-infarct related artery (non-IRA) lesions was performed. Patients with intermediate, non-critical lesions (FFR: 0.67-0.85) were included in this trial. For exploratory purpose, additional physiological assessment of the non-IRA included coronary flow reserve (CFR) and microvascular resistance index (IMR) measurements. Microvascular function was evaluated using a pressure- and temperature-sensitive guidewire and a bolus thermodilution method. Participants were randomized and treated for 12 weeks with either evolocumab or placebo in addition to high-intensity statin therapy. Staged reevaluation was done at 12 weeks. After repeated physiology testing, PCI was performed if deemed necessary. Pre-defined exploratory analysis includes the absolute and relative difference in change between CFR and IMR from baseline to follow up in the non-IRA. PCSK9 inhibition might result in a relatively larger increase of CFR and larger decrease of IMR. Results Between March 2020 and August 2023, a total of 150 patients were included in the trial. In 61 patients (88.5% male, age 65.3 ± 9.1 years, 23.0% STEMI, 70.5% non-STEMI, 6.6% UAP) successful baseline and follow-up measurements of microvascular function were performed. Complete results will be available at the beginning of March 2024. The primary- and secondary endpoints will be submitted for late-breaking clinical trials selection. The results of this abstract will include a per vessel analysis of coronary artery microvascular function. Conclusion The FITTER trial will provide new insights on the potential of extensive LDL-C reduction with a PCSK9 antibody on microvascular coronary artery function in patients presenting with ACS and MVD.

Clinical value of single projection angiography-derived FFR in non-infarct related artery

Abstract Background Murray law-based quantitative flow ratio (μFR) is an emerging technique which requires only one projection of coronary angiography with similar accuracy with quantitative flow ratio (QFR). However, it has not been validated for evaluation of non-infarct related artery (non-IRA) in acute myocardial infarction (AMI) setting. Therefore, our study aimed to evaluate the diagnostic accuracy of μFR and the safety of deferring non-IRA lesion with μFR>0.80 in the setting of AMI. Methods μFR and QFR were analyzed for non-IRA lesions of AMI patients enrolled in the FRAME-AMI trial, consisting of fractional flow ratio (FFR)-guided PCI and angiography-guided PCI groups. Diagnostic accuracy of μFR was compared to QFR and FFR. Patients were classified by non-IRA μFR values 0.80 as a cutoff value. The primary outcome was vessel-oriented composite outcomes (VOCO), a composite of cardiac death, non-IRA-related MI, and non-IRA-related repeat revascularization. Results 443 patients (552 lesions) were eligible for μFR and QFR analysis. μFR showed acceptable correlation with FFR (R=0.777, P<0.001), comparable C-index with QFR to predict FFR≤0.80 (μFR vs. QFR: 0.926 vs. 0.961, P=0.070), and shorter total analysis time (mean 32.7sec vs. 186.9sec, P<0.001). Non-IRA with μFR>0.80 and deferred PCI had significantly lower risk of VOCO than non-IRA with performed PCI (3.4% vs. 10.5%; HR, 0.37; 95% CI, 0.14-0.99; P=0.048). Conclusion In multivessel AMI patients, μFR of non-IRA showed acceptable diagnostic accuracy comparable to that of QFR to predict FFR≤0.80. Deferred non-IRA with μFR>0.80 showed lower risk of VOCO than revascularized non-IRA.

Three-Year Outcomes With Fractional Flow Reserve-Guided or Angiography-Guided Multivessel Percutaneous Coronary Intervention for Myocardial Infarction.

In patients with multivessel disease with successful primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction, the FLOWER-MI trial (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction) showed that a fractional flow reserve (FFR)-guided strategy was not superior to an angiography-guided strategy for treatment of noninfarct-related artery lesions regarding the 1-year risk of death from any cause, myocardial infarction, or unplanned hospitalization leading to urgent revascularization. The extension phase of the trial was planned using the same primary outcome to determine whether a difference in outcomes would be observed with a longer follow-up. In this multicenter trial, we randomly assigned patients with ST-segment-elevation myocardial infarction and multivessel disease with successful percutaneous coronary intervention of the infarct-related artery to receive complete revascularization guided by either FFR (n=586) or angiography (n=577). After 3 years, a primary outcome event occurred in 52 of 498 patients (9.40%) in the FFR-guided group and in 44 of 502 patients (8.17%) in the angiography-guided group (hazard ratio, 1.19 [95% CI, 0.79-1.77]; P=0.4). Death occurred in 22 patients (4.00%) in the FFR-guided group and in 23 (4.32%) in the angiography-guided group (hazard ratio, 0.96 [95% CI, 0.53-1.71]); nonfatal myocardial infarction in 23 (4.13%) and 14 (2.56%), respectively (hazard ratio, 1.63 [95% CI, 0.84-3.16]); and unplanned hospitalization leading to urgent revascularization in 21 (3.83%) and 18 (3.36%; hazard ratio, 1.15 [95% CI, 0.61-2.16]), respectively. Although event rates in the trial were lower than expected, in patients with ST-segment-elevation myocardial infarction undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction, or urgent revascularization up to 3 years. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02943954.

Clinical Value of Single-Projection Angiography-Derived FFR in Noninfarct-Related Artery.

The Murray law-based quantitative flow ratio (μFR) is an emerging technique that requires only 1 projection of coronary angiography with similar accuracy to quantitative flow ratio (QFR). However, it has not been validated for the evaluation of noninfarct-related artery (non-IRA) in acute myocardial infarction (AMI) settings. Therefore, our study aimed to evaluate the diagnostic accuracy of μFR and the safety of deferring non-IRA lesions with μFR >0.80 in the setting of AMI. μFR and QFR were analyzed for non-IRA lesions of patients with AMI enrolled in the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction), consisting of fractional flow reserve (FFR)-guided percutaneous coronary intervention and angiography-guided percutaneous coronary intervention groups. The diagnostic accuracy of μFR was compared with QFR and FFR. Patients were classified by the non-IRA μFR value of 0.80 as a cutoff value. The primary outcome was a vessel-oriented composite outcome, a composite of cardiac death, non-IRA-related myocardial infarction, and non-IRA-related repeat revascularization. μFR and QFR analyses were feasible in 443 patients (552 lesions). μFR showed acceptable correlation with FFR (R=0.777; P<0.001), comparable C-index with QFR to predict FFR ≤0.80 (μFR versus QFR: 0.926 versus 0.961, P=0.070), and shorter total analysis time (mean, 32.7 versus 186.9 s; P<0.001). Non-IRA with μFR >0.80 and deferred percutaneous coronary intervention had a significantly lower risk of vessel-oriented composite outcome than non-IRA with performed percutaneous coronary intervention (3.4% versus 10.5%; hazard ratio, 0.37 [95% CI, 0.14-0.99]; P=0.048). In patients with multivessel AMI, μFR of non-IRA showed acceptable diagnostic accuracy comparable to that of QFR to predict FFR ≤0.80. Deferred non-IRA with μFR >0.80 showed a lower risk of vessel-oriented composite outcome than revascularized non-IRA. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

The Presence of Chronic Total Occlusion in Noninfarct-Related Arteries Is Associated With Higher Mortality and Worse Patient Outcomes Following Percutaneous Coronary Intervention for STEMI: A Systematic Review, Meta-Analysis and Meta-Regression.

Reperfusion therapy with percutaneous coronary intervention improves outcomes in patients with ST-elevation myocardial infarction. We conducted a meta-analysis to assess the impact of chronic total occlusion (CTO) in noninfarct-related artery on the outcomes of these patients. Comprehensive searches were performed using PubMed, Google Scholar, and EMBASE. The primary endpoint was the 30-day mortality rate, with secondary endpoints including all-cause mortality, repeat myocardial infarction, and stroke. Forest plots were created for the pooled analysis of the results, with statistical significance set at P < 0.05. A total of 19 studies were included in this meta-analysis, with 23,989 patients (3589 in CTO group and 20,400 in no-CTO group). The presence of CTO was associated with significantly higher odds of 30-day mortality [18.38% vs 5.74%; relative risk (RR), 3.69; 95% confidence intervals (CI), 2.68-5.07; P < 0.00001], all-cause mortality (31.00% vs 13.40%; RR, 2.79; 95% CI, 2.31-3.37; P < 0.00001), cardiovascular-related deaths (12.61% vs 4.1%; RR, 2.61; 95% CI, 1.99-3.44; P < 0.00001), and major adverse cardiovascular events (13.64% vs 9.88%; RR, 2.08; 95% CI, 1.52-2.86; P < 0.00001) than the non-CTO group. No significant differences in repeated myocardial infarction or stroke were observed between the CTO and non-CTO groups. Our findings underscore the need for further research on the benefits and risks of performing staged or simultaneous percutaneous coronary intervention for CTO in the noninfarct-related artery in patients with ST-elevation myocardial infarction.

Reliability of Fractional Flow Reserve in Non-Infarct-Related Arteries in ST-Segment Elevation Myocardial Infarction Patients Undergoing a Pharmaco-Invasive Approach.

Objectives We investigated the reproducibility of fractional flow reserve (FFR) of significant stenoses (≥70% narrowing) in the non-infarct related artery (NIRA) during the pharmaco-invasive percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) within 24 hours of thrombolysis and at a follow up of 2-3 weeks. Background STEMI with multivessel disease has worse outcomes. The benefits of FFR-directed PCI of NIRA at the time of primary PCI are yet controversial. Assessing the hemodynamic severity of the NIRA may help in deciding the management strategy of these lesions, save time, and avoid complications. Methods Thirty-one patients undergoing PCI for STEMI under a pharmaco-invasive approach were prospectively recruited. The FFR measurements in 34 stenoses (≥70% diameter stenosis) were obtained immediately after PCI of the culprit stenosis and were repeated at a mean follow-up of 17.6± 3.55 (14-21) days. In addition, time to thrombolysis, time from symptom onset to PCI, left ventricular ejection fraction (LVEF), quantitative coronary angiographic measurements of the non-culprit stenoses, and thrombolysis in myocardial infarction (TIMI) flow were recorded. Results There was a significant change in FFR values at follow-up as compared to baseline (0.78 ± 0.08 (0.68-0.93) to 0.77 ± 0.08 (0.67-0.93)) (p = 0.014). In four of the lesions, the FFR values differed by >0.05 at follow-up. The follow-up FFR values led to a change in the management strategy in 5 out of 31 patients (15%) of the lesions. The TIMI flow, percentage diameter stenosis, minimum lumen diameter, and LVEF did not change. There were no predictors of this change in FFR values. Conclusions During the acute phase of STEMI, the severity of non-culprit coronary artery stenoses can not be reliably assessed by FFR. The prolonged jeopardized state of myocardium in pharmaco-invasive PCI as compared to primary PCI seems to be responsible.

Effect of alirocumab on quantitative flow ratio and diameter stenosis in non-infarct related arteries from patients with acute myocardial infarction: a PACMAN-AMI randomized clinical trial substudy

Abstract Introduction Treating hypercholesterolemia with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on top of statins leads to plaque regression and stabilization. The effects of PCSK9 inhibitors on coronary physiology and angiographic diameter stenosis (DS%) are unknown. Quantitative Flow Ratio (QFR) is a novel method to assess coronary hemodynamics. Purpose We aimed to investigate the effects of the PCSK9 inhibitor alirocumab on QFR and 3D-Quantitative Coronary Angiography (3D-QCA) DS% in non-infarct-related arteries (non-IRA) among acute myocardial infarction (AMI) patients. Methods This was a pre-specified substudy of the PACMAN trial, a randomized, double-blind, placebo-controlled trial comparing alirocumab vs. placebo on top of high-intensity rosuvastatin among AMI patients. QFR and 3D-QCA were assessed at baseline and 1-year follow-up in any non-infarct related artery (non-IRA) with ≥2.0mm diameter and &amp;gt;25% 3D-QCA DS%. The pre-specified primary endpoint was the number of patients with mean QFR increase from baseline to follow-up, and the secondary endpoint the change in 3D-QCA DS%. Results Of 300 enrolled patients, 265 had serial follow-up, of which 193 underwent serial QFR/3D-QCA analysis in 282 non-IRA. Baseline mean QFR was 0.96[IQR 0.91-0.98] and mean DS% 36.96±7.88% in the alirocumab group vs. 0.96[IQR 0.91-0.99] (p=0.593) and 36.63±8.46% (p=0.742) in the placebo group. At 1-year, QFR increased in 50/94 (53.2%) patients with alirocumab vs. 40/99 (40.4%) with placebo (Δ12.8%; OR=1.7, 95%CI 0.9-3.0; p=0.076). When excluding non-IRA with QFR &amp;gt;0.95, QFR increased in 37/57 (64.9%) patients with alirocumab vs. 22/50 (44.0%) with placebo (Δ20.9%; OR=2.4, 95%CI 1.1-5.2; p=0.031). DS% decreased by -1.03±7.28% with alirocumab and increased by +1.70±8.27% with placebo (Δ-2.54%, 95%CI -4.51 to -0.57; p=0.012). Conclusions Treatment of AMI patients with alirocumab vs. placebo for 1 year resulted in a significant regression in angiographic DS%. While no overall improvement of coronary hemodynamics was observed with alirocumab as compared to placebo, potential benefits were found in alirocumab treated patients with baseline QFR ≤0.95.Figure 1.Flowchart and primary endpointFigure 2.Secondary endpoint

The impact of ticagrelor therapy on CABG-related bleeding in patients with STEMI managed with pPCI

Abstract Background Patients on double antiplatelet treatment who need early in-hospital coronary artery bypass grafting (CABG) are at high risk of major bleeding. However, recent studies have demonstrated that early CABG surgery within 7 days of discontinuation of p2Y12 inhibitors are safe with respect to bleeding events in patients with acute coronary syndrome. Purpose In this study, we aimed to investigate the impact of ticagrelor preloading on CABG related bleeding in patients with ST-segment elevation myocardial infarction (STEMI) initially managed with primary percutaneous coronary intervention (pPCI). Methods Patients with the diagnosis of STEMI who were managed with pPCI and underwent subsequent early (4-7 days following pPCI) or delayed (&amp;gt; 7 days following pPCI) CABG surgery were included. All study patients were preloaded with ticagrelor 180 mg prior to pPCI procedure. Patients’ demographics, clinical variables and short-term cardiovascular outcomes were recorded. Results The study cohort included 98 patients. Fifty-four (54%) patients underwent early and 44(45%) patients underwent delayed CABG surgery. Left main coronary artery involvement and presence of chronic total occlusion in the non-infarct related artery were 26.5% and 25.5%. CABG-related bleeding occurred in 22 (22.4%) patients. There was no significant difference with respect to total ticagrelor dose and timing of the surgery between patients with or without CABG-related bleeding (p: 0.165 and p:0.142). Multivariate analyses demonstrated that only preoperative hemoglobin level was an independent predictor of CABG-related bleeding (OR:0.720, p: 0.034).There were three deaths within the 30 days of surgery, all occurring in patients with CABG-related bleeding. However, CABG-related bleeding was not associated with long-term cardiovascular events during the follow-up. Conclusion Our results indicated that discontinuation of ticagrelor therapy 3 days prior to surgery is sufficient to avoid CABG-related bleeding. Moreover, early CABG following STEMI does not increase the risk of long-term cardiovascular events.

Prognosis after non-infarct related artery PCI in patients with acute myocardial infarction and multivessel disease: substudy of FRAME-AMI trial

Abstract Background Complete revascularization either angiography-guided or fractional flow reserve (FFR)-guided can improve the clinical outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, there is concern that angiography-guided percutaneous coronary intervention (PCI) may result in unnecessary PCI of non-infarct related artery (IRA) and its long-term prognosis is still unclear. Purpose We sought to evaluate clinical outcomes after non-IRA PCI according to quantitative flow ratio (QFR). Methods We performed post-hoc QFR analysis of non-IRA lesions of AMI patients who enrolled in the FRAME-AMI trial which randomly allocated patients into either FFR-guided PCI (FFR≤0.80) or angiography-guided PCI (diameter stenosis of &amp;gt;50%) for non-IRA lesions. Patients were classified by non-IRA QFR values into the QFR≤0.80 and QFR&amp;gt;0.80 groups. The primary end point was a major adverse cardiac event (MACE), a composite of cardiac death, MI, and repeat revascularization. Results A total of 443 patients (552 lesions) were eligible for the QFR analysis. Of 209 patients in the angiography-guided PCI group, 30.0% (N=60) underwent non-IRA PCI despite having QFR&amp;gt;0.80 in non-IRA. Conversely, only 2.7% (N=4) among 209 patients in the FFR-guided PCI group had QFR&amp;gt;0.80 in non-IRA. At a median follow-up of 3.5 years (interquartile range 2.7 to 4.1 years), the rate of MACE was significantly higher among patients with non-IRA PCI despite QFR&amp;gt;0.80 than patients with deferred PCI for non-IRA lesions (12.9% vs. 3.1%; HR=4.13, 95% CI 1.10-15.57, P=0.036). Non-IRA PCI despite QFR&amp;gt;0.80 was associated with higher risk of non-IRA MACE than patients with deferred PCI for non-IRA lesions (12.9% vs. 2.1%; HR 5.44, 95% CI 1.13-26.19, P=0.035). Conclusions In AMI patients with multivessel disease, 30.0% of angiography-guided PCI resulted in unnecessary PCI for non-IRA with QFR&amp;gt;0.80, which was significantly associated with the increased risk of MACE than those with deferred PCI for non-IRA lesions.

Differential outcomes in FFR-guided versus angiography-guided revascularization strategy according to target non-infarct related vessels: from FRAME-AMI trial

Abstract Background Incomplete revascularization of non-infarct related arteries (IRA) leads to worse outcomes in patients with acute myocardial infarction (AMI) and multivessel coronary artery disease (MVD). Outcomes of fractional flow reserve (FFR)- and angiography-guided percutaneous coronary intervention (PCI) for non-IRA may differ according to their location between the anterior descending artery (LAD) and non-LAD. Aims We investigated the impact of FFR- versus angiography-guided PCI on clinical outcomes according to the location of non-IRA (LAD versus non-LAD) in AMI patients with MVD. Methods This trial was a pre-specified post-hoc analysis of the FRAME-AMI study, an investigator-initiated, randomized, open-label, multicenter trial at 14 sites in Korea. In the FRAME-AMI trial, PCI was performed for non-IRA in 64.1% (FFR £0.80) and 97.1% (diameter stenosis of &amp;gt;50%) in FFR-guided PCI and angiography-guided PCI groups, respectively. We grouped the patients into four according to treatment strategy (FFR versus angiography) and location of non-IRA (LAD vs. non-LAD). The primary endpoint was a composite of time to death, MI, or repeat revascularization. Results Patients with non-IRA involving LAD and non-LAD were 55.0% and 45.0%, respectively. The proportion of performed PCI (82.2% vs. 78.3%, p=0.242) and the rate of the primary outcome (9.4% vs. 11.5%, p=0.421) were similar between LAD and non-LAD. Among patients with non-IRA involving LAD, the FFR-guided group had a fewer events rate of the primary outcome than the angiography-guided group (5.7% vs. 14.3%, p=0.010). Among those with non-IRA not involving LAD, the FFR-guided group tended to the lower incidence of the primary outcome compared to the angiography-guided group (7.4% vs. 14.5%, p=0.081). However, the effect of the interaction between LAD and non-LAD on the primary outcome was not found (p for interaction 0.667). Conclusions In AMI patients with MVD, FFR-directed PCI for non-IRA was superior to angiography-guided PCI regardless of the location of non-IRA. The benefit of an FFR-directed revascularization strategy for non-IRA is likely enhanced in LAD.

Abstract 15023: Fractional Flow Reserve-Guided Complete Revascularization in AMI Patients With Angiographically Severe Non-Culprit Lesion: FRAME-AMI Substudy

Background: The benefit of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for non-culprit lesions with angiographically severe stenosis in patients with acute myocardial infarction (AMI) is unclear Objectives We evaluated the relationship between non-culprit lesion stenosis measured by quantitative coronary angiography (QCA) and the efficacy of FFR-guided PCI Methods: Severity of non-culprit lesion stenosis of 562 patients from FRAME-AMI (FFR vs. Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients with AMI) was measured using QCA in the core laboratory. The effect of FFR-guided versus angiography-guided PCI according to non-culprit lesion stenosis (QCA stenosis ≥70% or &lt;70%) on the primary end point (risk of death, MI or repeat revascularization) was analyzed Results: At a median follow-up of 3.5 years, the primary end point occurred in 14 patients of 181 patients with FFR-guided PCI and 31 of 197 patients with angiography-guided PCI among patient with QCA stenosis ≥70% (7.7% vs 15.7%; hazard ratio, 0.48; 95% confidence interval, 0.25 to 0.90; P=0.022), while occurred in 4 of 103 patients with FFR-guided PCI and 9 of 81 patients with angiography-guided PCI among those with QCA stenosis &lt; 70% (3.9% vs 11.1%, p=0.079). FFR-guided PCI was associated with the reduction of death and myocardial infarction in patients with QCA stenosis ≥70% (6.1% vs 13.7%, p=0.019) and those with QCA stenosis &lt; 70% (1.0% vs 9.9%, p=0.028) compare to angiography-guided PCI Conclusions: In patients with AMI and multivessel disease, patients with severe non-infarct related artery lesion was also benefited by FFR-guided PCI.

Angiographic Severity of the Nonculprit Lesion and the Efficacy of Fractional Flow Reserve-Guided Complete Revascularization in Patients With AMI: FRAME-AMI Substudy.

The benefit of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for noninfarct-related artery (IRA) lesions with angiographically severe stenosis in patients with acute myocardial infarction is unclear. Among 562 patients from the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infraction Related Artery Stenosis in Patients With Acute Myocardial Infarction) who were randomly allocated into either FFR-guided or angiography-guided PCI for non-IRA lesions, the current study evaluated the relationship between non-IRA stenosis measured by quantitative coronary angiography (QCA) and the efficacy of FFR-guided PCI. The incidence of the primary end point (death, myocardial infarction, or repeat revascularization) was compared between FFR- and angiography-guided PCI according to non-IRA stenosis severity (QCA stenosis ≥70% or <70%). A total of 562 patients were assigned to FFR-guided (n=284) versus angiography-guided PCI (n=278). At a median follow-up of 3.5 years, the primary end point occurred in 14 of 181 patients with FFR-guided PCI and 31 of 197 patients with angiography-guided PCI among patients with QCA stenosis ≥70% (8.5% versus 19.2%; hazard ratio, 0.41 [95% CI, 0.22-0.80]; P=0.008), while occurred in 4 of 103 patients with FFR-guided PCI and 9 of 81 patients with angiography-guided PCI among those with QCA stenosis <70% (3.9% versus 11.1%; P=0.315). There was no significant interaction between treatment strategy and non-IRA stenosis severity (P for interaction=0.636). FFR-guided PCI was associated with the reduction of death and myocardial infarction in both patients with QCA stenosis ≥70% (6.7% versus 15.1%; P=0.008) and those with QCA stenosis <70% (1.0% versus 9.6%; P=0.042) compared with angiography-guided PCI. In patients with acute myocardial infarction and multivessel disease, FFR-guided PCI tended to have a lower risk of primary end point than angiography-guided PCI regardless of non-IRA stenosis severity without significant interaction. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

TCT-62 Prognosis After Noninfarct-Related Artery PCI in Patients With Acute Myocardial Infarction and Multivessel Disease

TCT-62 Prognosis After Noninfarct-Related Artery PCI in Patients With Acute Myocardial Infarction and Multivessel Disease

The Inhibition of Evolocumab on Non-Infarct-Related Artery Disease in Patients with ST-Elevation Myocardial Infarction.

The effects of combing evolocumab and statin on the clinical outcome and physiological function of coronary arteries in STEMI patients with non-infarct-related artery (NIRA) disease are still unclear. A total of 355 STEMI patients with NIRA were enrolled in this study, who underwent combined quantitative flow ratio (QFR) at baseline and after 12 months of treatment with statin monotherapy or statin plus evolocumab. Diameter stenosis and lesion length were significantly lower in the group undergoing statin plus evolocumab. While the group exhibited significantly higher minimum lumen diameter (MLD), and QFR values. Statin plus evolocumab (OR = 0.350; 95% CI: 0.149-0.824; P = 0.016) and plaque lesion length (OR = 1.223; 95% CI: 1.102-1.457; P = 0.033) were independently associated with rehospitalization for unstable angina (UA) within 12 months. Evolocumab combined with statin therapy can significantly improve the anatomical and physiological function of the coronary arteries and downregulate the re-hospitalization rate due to UA in STEMI patients with NIRA.

Infarct-Related Artery as aDonor of Collaterals in ST-Segment-Elevation Myocardial Infarction With Concomitant Chronic Total Occlusion: Challenge of the Double-Jeopardy Thesis.

BACKGROUND In ST-segment-elevation myocardial infarction (STEMI), a concomitant chronic total occlusion (CTO) in a non-infarct-related artery (NIRA) is associated with adverse outcome. In the case of the infarct-related artery (IRA) as a donor vessel for collaterals to the CTO, the IRA occlusion may lead to an acute threat to both the immediate IRA and the collaterally supplied CTO area, which has been described as a double-jeopardy effect. METHODS AND RESULTS We investigated the role of preformed intercoronary collaterals to the CTO originating from either the IRA or NIRA. Data were obtained from 2 hospitals participating in the prospective FITT-STEMI (Feedback Intervention and Treatment Times in ST-Segment Elevation Myocardial Infarction) study. From a total cohort of 2102 patients with acute STEMI, 93 patients had single-vessel CTO in an NIRA and well-developed intercoronary collaterals to the CTO. In-hospital mortality differed significantly with respect to the origin of the collaterals. Mortality was 15.2% with collaterals originating from the NIRA, 29.4% with a collateral origin from the IRA proximal to the acute STEMI occlusion, and 3.3% with a collateral origin from the IRA distal to the acute occlusion (P=0.044). A multivariate regression model confirmed that a proximal collateral origin had a significant higher mortality compared with a branching in the distal position from the acute STEMI occlusion (P=0.027; odds ratio=20.8 [95% CI, 1.4-304.1]). CONCLUSIONS In STEMI with CTO in an NIRA, a CTO collateralization from the IRA distal to the acute occlusion is associated with a better prognosis. This finding challenges the double-jeopardy assumption as the main cause of adverse outcome in STEMI with CTO in an NIRA. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT00794001.

Effect of combined lipid-lowering therapy on atherosclerotic plaque vulnerability in patients with acute coronary syndrome (Combi-LLT ACS): randomized trial protocol

Aim. To study the effect of high-dose combined lipid-lowering therapy (statins + ezetimibe vs statins + PCSK9 inhibitors) on plaque vulnerability assessed using multimodal imaging (coronary computed tomography angiography (CCTA) and optical coherence tomography, as well as biomarkers in patients with acute coronary syndrome (ACS).Material and methods. This open, prospective, randomized, single-center study will include 120 patients admitted urgently with an ACS. All patients will undergo percutaneous coronary intervention of the infarct-related artery, as well as intracoronary imaging using optical coherence tomography of one or two noninfarct-related arteries. During hospitalization, patients will receive standard therapy for ACS according to clinical guidelines, while statins will initially be prescribed at a maximum dosage of atorvastatin 80 mg/rosuvastatin 40 mg.Patients who showed high compliance and did not reach the target low-density lipoprotein cholesterol (LDL-C) values (≤1,4 mmol/l) 1 month after myocardial infarction/unstable angina at the second visit will be randomized into two groups. Patients of group 1 will receive PCSK9 inhibitors (alirocumab 150 mg by subcutaneous injection once every 2 weeks or evolocumab 140 mg by subcutaneous injection once every 2 weeks) in addition to maximum statin therapy (atorvastatin 80 mg/rosuvastatin 40 mg), while group 2 participants will take ezetimibe at a dose of 10 mg in combination with the maximum dose of statins. In addition, at the second visit, patients will undergo CCTA, assess the cardio-ankle vascular index (CAVI) index and laboratory tests (complete blood count (neutrophil-to-lymphocyte ratio NLR), lipid profile, alanine aminotransferase (ALT), aspartate aminotransferase (AST), Troponin I, Galectin-3, high-sensitivity C-reactive protein (hs-CRP), metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL). Total follow-up will last 52 weeks. At the final visit, patients will undergo CCTA, assessment of the CAVI index and laboratory status (NLR, lipid profile, ALT, AST), Troponin I, Galectin-3, hs-CRP, MMP-9, TIMP-1, NGAL).Primary endpoint: reduction in plaque vulnerability according CCTA in non-infarct-related coronary arteries Secondary endpoints: death, stent thrombosis/restenosis, non-fatal myocardial infarction, readmissions with progressive angina, repeat revascularization; changes of the lipid profile (total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides) against the background of maximum combination therapy with statin + PCSK9 inhibitors or statin + ezetimibe; changes of the biomarkers of cardiac injury (Troponin I), inflammation (NLR, hs-CRP, NGAL, Galectin-3) and matrix remodeling (MMP-9, TIMP-1).Conclusion. Our study will allow for the first time to compare and evaluate the effect of both PCSK9 inhibitors and ezetimibe in combination with high-dose statin therapy on reducing the plaque vulnerability according to CCTA in non-infarction-related coronary arteries in patients with ACS undergoing percutaneous coronary intervention, as well as to evaluate the diagnostic value of inflammatory biomarkers (NLR, hs-CRP, NGAL, Galectin-3) and matrix remodeling (MMP-9, TIMP-1).

Abstract 14701: Angiographic and Prognostic Difference of Acute Myocardial Infarction Patients With and Without Out of Hospital Cardiac Arrest Stratified by Killip Classification

Backgrounds: Although the mortality rates for AMI have declined, the mortality rate for AMI with out-of-hospital cardiac arrest (OHCA) remains high. It has been supposed that CTO (chronic total occlusion) in non-infarct related artery is associated with OHCA patients. However, the detailed angiographic and prognostic comparison between OHCA patients and non-OHCA patients stratified by Killip classification has not been well evaluated. Methods: Among 5662 AMI patients (5420 non-OHCA patients and 242 OHCA patient) who underwent emergency coronary angiography between 2013 and 2020 were enrolled from Mie ACS registry. Difference of culprit lesion and non-infarct related CTO lesion were analyzed between with and without OHCA. They were further stratified using Killip classification. Results: In-hospital mortality for AMI patients with OHCA was 31.4%, significantly higher than the 5.5% for AMI patients with non-OHCA (p&lt;0.001), and mortality rates tended to be increased with increasing Killip class in each group(P&lt;0.001). AMI patients with OHCA also had a significantly higher frequency of culprit artery with LMT and LAD and a higher frequency of CTO lesion in non-infarct related artery compared to the AMI patients with non-OHCA.(See Table) Multivariate analysis revealed that LAD CTO in non-infarct related artery(Odds ratio 2.3) culprit artery of LMT and LAD (Odds ratio 3.2 and 1.6), lower BMI(Odds ratio 0.96), younger age(Odds ratio 0.98) and male gender (Odds ratio 1.7)was significantly associated with OHCA(P&lt;0.05, respectively). However, non-LAD CTO lesion in non-infarct related artery was not associated with OHCA Conclusions: Patients with OHCA had a higher incidence of culprit artery with LMT and LAD, and non-infarct-related LAD CTO lesion, suggesting that extensive myocardial ischemia with LAD lesion was strongly associated with OHCA.

Abstract 10553: Staged Percutaneous Coronary Intervention For Chronic Total Occlusion of Non-Infarct Related Artery: A Meta-Analysis

Background: Chronic total occlusion (CTO) of a non-infarct related artery (nIRA) is associated with adverse outcomes following acute myocardial infarction (AMI). The current study aimed to evaluate the impact of successful staged percutaneous coronary intervention (PCI) of nIRA CTO lesions on clinical outcomes. Methods: PubMed, EMBASE, Google Scholar and Scopus databases were queried for studies comparing outcomes between AMI patients who underwent successful staged PCI of nIRA CTO lesions (CTO PCI group) and AMI patients with medical management of nIRA CTO lesions or failed CTO PCI attempt (No CTO PCI group). The primary meta-analysis outcome was major adverse cardiovascular events (MACE). The main summary estimate was the random effects risk ratio (RR) with 95% confidence intervals (CIs). Results: Eleven studies (1 randomized, 10 observational) with 2,788 patients were included. Compared with the No CTO PCI group, the CTO PCI group demonstrated a lower incidence of MACE (Figure A, RR 0.55 [0.46, 0.66], p&lt;0.001), all-cause mortality (Figure B, RR 0.47 [0.33, 0.66], p&lt;0.001), cardiac mortality (Figure C, RR 0.4 [0.28, 0.59], p&lt;0.001), stroke (Figure D, RR 0.38 [0.22, 0.66], p=0.0007) and heart failure (HF) hospitalization (RR 0.61 [0.41, 0.9], p=0.01). There was no significant difference in rates of any repeat revascularization (Figure E, RR 0.98 [0.69, 1.4], p=0.92) or target vessel revascularization (Figure F, RR 0.81 [0.48, 1.37], p=0.43) between the two groups. Conclusion In patients with AMI, staged PCI of nIRA CTO lesions was associated with a significantly lower incidence of MACE, all-cause mortality, cardiac mortality, stroke and HF hospitalization.

Outcome of ST-segment elevation myocardial infarction (STEMI) patients with significant non-infarct related artery (IRA) lesions

Abstract Funding Acknowledgements Type of funding sources: None. Background Multivessel disease is common (50%) in patients presenting with ST-segment elevation myocardial infarction (STEMI), and this is associated with a higher mortality compared to single-vessel disease. The optimal timing for revascularisation of significant non-infarct related artery (IRA) (non-culprit) lesions in STEMI patients remains controversial. The two main approaches include immediate revascularisation during the primary percutaneous coronary intervention (PPCI) or deferred (48 hours after the index procedure) percutaneous coronary intervention (PCI). The European Society of Cardiology guidelines recommend consideration of immediate non-IRA PCI in STEMI patients with cardiogenic shock, while revascularisation of other patients with non-IRA significant lesions should be considered prior to hospital discharge. Purpose To determine the optimal timing of intervention of significant non-IRA lesions in patients presenting with STEMI. Methods Coronary angiograms of nationwide STEMI patients who underwent a PPCI between 2013 and 2017 were reviewed to determine whether a significant non-IRA lesion was present (defined as &amp;gt;70% stenosis, or &amp;gt;50% of left main stem). The patients were divided into Group 1: immediate PCI of the non-IRA lesion during the PPCI, and Group 2: deferred PCI of non-IRA lesion prior to hospital discharge. Patients were followed up till end 2020 to determine whether a major adverse cardiovascular event occurred (death, myocardial infarction [MI], hospitalization due to pulmonary oedema and revascularization with repeat PCI and coronary artery bypass [CABG]). Chi-square and Fisher’s exact test were used for statistical analysis. Results 1080 patients underwent a PPCI between 2013 and 2017. 578 patients were excluded as they had no bystander disease, and a further 340 were excluded as they underwent CABG or medical treatment for the non-IRA lesions. From the remaining cohort, 55 patients were stratified to group 1 and 107 patients in group 2. There were no significant differences in baseline characteristics (Picture 1). Picture 2 demonstrates the distribution of non-IRAs which required PCI. Patients who had immediate non-IRA lesion PCI had a significantly higher mortality (Group 1, 21.8% vs Group 2, 8.4%, p=0.016) and more admissions with pulmonary oedema (Group 1, 10.9% vs Group 2, 0.9%, p=0.006). Group 1 patients were found to have a higher occurrence of cardiac arrest during the PPCI (10.9% vs 0.9%, p=0.006) and cardiogenic shock (12.7% vs 3.7%, p=0.046). There were no differences with regards to angina (p=0.386), MI (p=0.426) or re-vascularisation with repeat PCI (p= 0.090) or CABG (p=0.114). Conclusion STEMI patients who underwent immediate PCI to non-IRA lesions had a poorer outcome with higher rates of mortality and pulmonary oedema admissions compared to the deferred PCI cohort. Large randomised controlled trials are required to determine the optimal timing for intervention of significant non-IRA lesions.

Primary Percutaneous Intervention for ST-Elevation Myocardial Infarction Patients: A State of The Art

Primary PCI is the preferred reperfusion strategy in patients with STEMI within 12 h of symptom onset. Angiographically successful PPCI was defined as less than 30% residual stenosis by visual assessment and grade 3 TIMI flow achievement. Radial access is preferred over femoral access. Drug eluting stent (DES) implantation is more superior than bare metal stent (BMS) implantation or balloon angioplasty. In STEMI patients with cardiogenic shock, non-infarct related artery PCI during the index procedure should be considered.