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Background ST-segment elevation myocardial infarction (STEMI) patients are treated with dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor. Clopidogrel is widely used in these patients in several areas worldwide, such as Middle East, but is associated to sub-optimal platelet inhibition in up to 1/3 of treated patients. We investigated a CYP2C19 genotype-guided strategy to select the optimal P2Y12 inhibitor. Methods This prospective randomized clinical trial included STEMI patients. The standard-treatment group received clopidogrel, while the genotype-guided group were genotyped for CYP2C19 loss-of-function alleles and carriers were prescribed ticagrelor and noncarriers were prescribed clopidogrel. Primary outcome was a combined ischemic and bleeding outcome, comprising myocardial infarction, non-fatal stroke, cardiovascular death, or Platelet Inhibition and Patient Outcomes major bleeding one year after STEMI. Results STEMI patients (755) were randomized into a genotype-guided- (383) and standard-treatment group (372). In the genotype-guided group, 31 patients carrying a loss-of-function allele were treated with ticagrelor, while all other patients in both groups were treated with clopidogrel. Patients in the genotype-guided group had a significantly lower risk of primary outcome (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.20–0.59,), recurrent myocardial infarction (OR 0.25, 95%CI 0.11–0.53), cardiovascular death (OR 0.16, 95%CI0.06–0.42) and major bleeding (OR 0.49, 95%CI 0.32–0.74). There was no significant difference in the rate of stent thrombosis (OR 0.85, 95%CI 0.43–1.71). Conclusion A genotype-guided escalation of P2Y12 inhibitor strategy is feasible in STEMI patients treated with clopidogrel and undergoing PCI and is associated with a reduction of primary outcomes compared to conventional antiplatelet therapy.

Background Chronic obstructive pulmonary disease (COPD) is projected to become the third cause of mortality worldwide. COPD shares several pathophysiological mechanisms with cardiovascular disease, especially atherosclerosis. However, no definite answers are available on the prognostic role of COPD in the setting of ST elevation myocardial infarction (STEMI), especially during COVID-19 pandemic, among patients undergoing primary angioplasty, that is therefore the aim of the current study. Methods In the ISACS-STEMI COVID-19 registry we included retrospectively patients with STEMI treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 from 109 high-volume primary PCI centers in 4 continents. Results A total of 15,686 patients were included in this analysis. Of them, 810 (5.2%) subjects had a COPD diagnosis. They were more often elderly and with a more pronounced cardiovascular risk profile. No preminent procedural dissimilarities were noticed except for a lower proportion of dual antiplatelet therapy at discharge among COPD patients (98.9% vs. 98.1%, P = 0.038). With regards to short-term fatal outcomes, both in-hospital and 30-days mortality occurred more frequently among COPD patients, similarly in pre-COVID-19 and COVID-19 era. However, after adjustment for main baseline differences, COPD did not result as independent predictor for in-hospital death (adjusted OR [95% CI] = 0.913[0.658–1.266], P = 0.585) nor for 30-days mortality (adjusted OR [95% CI] = 0.850 [0.620–1.164], P = 0.310). No significant differences were detected in terms of SARS-CoV-2 positivity between the two groups. Conclusion This is one of the largest studies investigating characteristics and outcome of COPD patients with STEMI undergoing primary angioplasty, especially during COVID pandemic. COPD was associated with significantly higher rates of in-hospital and 30-days mortality. However, this association disappeared after adjustment for baseline characteristics. Furthermore, COPD did not significantly affect SARS-CoV-2 positivity. Trial registration number: NCT 04412655 (2nd June 2020).

BACKGROUND: Clonal haematopoiesis driven by mutations in DNMT3A or TET2 has recently been identified as a new risk factor for cardiovascular disease. Experimental studies suggest that these mutations may enhance inflammation which accelerates the disease progression. We aim to investigate the prevalence of mutations in DNMT3A and TET2 and their association with prognosis of patients with ST-segment elevation myocardial infarction (STEMI).METHODS: Targeted deep sequencing for DNMT3A and TET2 and inflammatory cytokines (IL-1β, IL-6, TNF-α, INF-γ) were analyzed in 485 patients with STEMI. Major adverse cardiac events (MACE) was a composite of death, myocardial infarction, stroke, or hospitalization due to heart failure.FINDINGS: Patients carrying DNMT3A- or TET2-CH-driver mutations with a variant allele frequency (VAF) ≥2% were found in 12.4% (60 of 485) of STEMI patients and experienced an increased incidence of the death (30.9% vs 15.5%, P = 0.001) and MACE (44.5% vs 21.8%, P < 0.001) compared to those who did not, during a median follow up of 3.0 (interquartile range: 2.4-3.4) years. After adjusting for confounders, mutation remained an independent predictor of death (HR = 1.967, 95% CI 1.103-3.507, P = 0.022) and MACE (HR = 1.833, 95% CI 1.154-2.912, P = 0.010). Concentrations of plasma IL-1β (P = 0.010) and IL-6 (P = 0.011) were significantly elevated in DNMT3A/TET2 VAF≥2% group.INTERPRETATION: DNMT3A- or TET2-CH-driver mutations with a VAF≥2% were observed in over 10% STEMI patients, and were significantly associated with poorer prognosis, which might be explained by higher levels of inflammatory cytokines in mutations carriers.FUNDING: National Natural Science Foundation of China; National Key R&D Program of China.

Aims Stent implantation during primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) occasionally results in flow disturbances and distal embolization, which may cause adverse clinical outcomes. Deferred stent implantation seems to reduce the impairment on myocardial function, although the mechanisms have not been clarified. We sought to evaluate whether deferred stenting could reduce flow disturbance in patients treated with primary PCI. Methods and results Patients with STEMI included in the DANAMI-3-DEFER trial were randomized to deferred versus immediate stent implantation. The primary and secondary outcomes of this substudy were the incidences of slow/no reflow and distal embolization. A total of 1205 patients were included. Deferred stenting (n = 594) resulted in lower incidences of distal embolization [odds ratio (OR) 0.67, 95% confidence interval (CI) 0.46–0.98, P = 0.040] and slow/no reflow (OR 0.60, 95%CI 0.37–0.97, P = 0.039). In high-risk subgroups, the protective effect was greatest in patients >65 years of age (slow/no reflow: OR 0.36, 95% CI 0.17–0.72, P = 0.004 and distal embolization: OR 0.34, 95% CI 0.18–0.63, P = 0.001), in patients presenting with occluded culprit artery at admission (slow/no reflow: OR 0.33, 95% CI 0.16–0.65, P = 0.001 and distal embolization: OR 0.54, 95% CI 0.31–0.96, P = 0.036) and in patients with thrombus grade >3 (slow/no reflow: OR 0.37, 95% CI 0.20–0.67, P = 0.001 and distal embolization: OR 0.39, 95% CI 0.24–0.64, P < 0.001) with a significant P for interaction for all. Conclusion Deferred stent implantation reduces the incidences of slow/no reflow and distal embolization, especially in older patients and in those with total coronary occlusion or high level of thrombus burden.

ObjectiveThe initial data of the International Study on Acute Coronary Syndromes - ST Elevation Myocardial Infarction COVID-19 showed in Europe a remarkable reduction in primary percutaneous coronary intervention procedures and higher in-hospital mortality during the initial phase of the pandemic as compared with the prepandemic period. The aim of the current study was to provide the final results of the registry, subsequently extended outside Europe with a larger inclusion period (up to June 2020) and longer follow-up (up to 30 days).MethodsThis is a retrospective multicentre registry in 109 high-volume primary percutaneous coronary intervention (PPCI) centres from Europe, Latin America, South-East Asia and North Africa, enrolling 16 674 patients with ST segment elevation myocardial infarction (STEMI) undergoing PPPCI in March/June 2019 and 2020. The main study outcomes were the incidence of PPCI, delayed treatment (ischaemia time >12 hours and door-to-balloon >30 min), in-hospital and 30-day mortality.ResultsIn 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio 0.843, 95% CI 0.825 to 0.861, p75 years) (p=0.015), and was not related to the peak of cases or deaths due to COVID-19. The heterogeneity among centres was high (pConclusionPercutaneous revascularisation for STEMI was significantly affected by the COVID-19 pandemic, with a 16% reduction in PPCI procedures, especially among older patients (about 20%), and longer delays to treatment, which may have contributed to the increased in-hospital and 30-day mortality during the pandemic.Trial registration numberNCT04412655.

In ST-elevation myocardial infarction (STEMI), early restoration of blood flow, preferably by primary percutaneous coronary intervention (PPCI), is paramount to limit infarct size (IS) and improve long-term outcomes 1. However, reperfusion by itself may also cause damage to the myocardium and increase IS. This has been termed myocardial reperfusion injury 2. In animal models of acute myocardial infarction, it has been demonstrated that hypothermia decreases IS 3. In contrast, human studies applying systemic cooling methods have not yet been able to confirm this protective effect. Recently, we developed a new method to provide selective intracoronary hypothermia during PPCI 4. The EUROpean Intracoronary Cooling Evaluation in patients with ST-elevation myocardial infarction (EURO-ICE) trial will assess the efficacy of this method. Methods STUDY OBJECTIVES The primary objective of the EURO-ICE trial is to evaluate the effect of selective intracoronary hypothermia (SIH) on IS.

Background and aims SARS-Cov-2 predisposes patients to thrombotic complications, due to excessive inflammation, endothelial dysfunction, platelet activation, and coagulation/fibrinolysis disturbances. The aim of the present study was to evaluate clinical characteristics and prognostic impact of SARS-CoV-2 positivity among STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Methods We selected SARS-CoV-2 positive patients included in the ISACS-STEMI COVID-19, a retrospective multicenter European registry including 6609 STEMI patients treated with PPCI from March 1st until April 30th, in 2019 and 2020. As a reference group, we randomly sampled 5 SARS-Cov-2 negative patients per each SARS-CoV-2 positive patient, individually matched for age, sex, and hospital/geographic area. Study endpoints were in-hospital mortality, definite stent thrombosis, heart failure. Results Our population is represented by 62 positive SARS-CoV-2 positive patients who were compared with a matched population of 310 STEMI patients. No significant difference was observed in baseline characteristics or the modality of access to the PCI center. In the SARS-CoV-2 positive patients, the culprit lesion was more often located in the RCA (p, Graphical abstract Image 1

International audience; Background: Different mortality rates are reported in registries of patients with ST-segment elevation myocardial infarction (STEMI), but comparisons between registries are challenging. Aims: To determine whether the higher mortality rate in our regional French registry (SCALIM) is related to different inclusion criteria and demographic characteristics. Methods: The SCALIM registry included all patients with STEMI within the first 24 h in the region of Limousin, France (06/2011-01/2015). To compare mortality rates with other contemporary registries in France and European neighbouring countries, the others' inclusion criteria were applied to the SCALIM registry. Results: Among 1501 patients included, in-hospital and 1-month mortality were 8.2% and 8.8% respectively, significantly higher than many other registries. The use of inclusion criteria from EMUST (France), MINAP (UK) or LOMBARDIMA (Italy) markedly decreased the number of enrolled patients by 64%, 36%, and 21%, respectively. When those inclusion criteria were applied to the SCALIM registry, difference in in-hospital and 1-month mortality rates between other registries and ours remained significant. In the multivariate analysis, age, initial acute pulmonary oedema (Killip class ≥2), complication occurring before percutaneous coronary intervention, absence of transfer to an interventional cardiology centre for primary angioplasty and lack of reperfusion therapy within 12 h were associated with higher risk of 1-month mortality (all p < 0.05). Age (65 versus 63.3 years, p < 0.001) was higher and reperfusion rate (84.2 versus 74.7%, p < 0.001) was significantly lower in SCALIM than FAST-MI, the national French registry on STEMI patients. Interestingly, the 3% of patients included in SCALIM who would be excluded from FAST-MI registry had 91% mortality at one month. Conclusion: Higher mortality rate in our regional SCALIM registry is in part due to differences in inclusion criteria and demographic data. Consensus should be made to harmonise inclusion criteria in STEMI registries for the sake of comparability.

International audience; Background: The delay between the occurrence of symptoms and the call seeking medical assistance is an important component of the pain-to-balloon delay in patients with ST-segment elevation myocardial infarction (STEMI). Factors affecting this "patient delay" have been poorly studied, and campaigns to raise emergency call awareness have barely been evaluated. Aims: To evaluate the factors related to patient delay, and the effects of public awareness campaigns undertaken in our region. Methods: Data from the regional registry of STEMI in Limousin, France, were analysed, and we performed a survey to assess medical history, clinical signs, context, socioeconomic situation and perception and behaviour of the patient. "Late callers" (i.e. third tertile,>154minutes) were compared with "early callers" (i.e. first and second tertiles,≤154minutes) using univariate and multivariable statistical methods. The influence of public awareness campaigns was studied by comparing the patient delays before and after a regional campaign. Results: Among 481 patients, the median patient delay was 87minutes. "Late callers" were older (odds ratio [OR] 1.02 per year, 95% confidence interval [CI] 1.00 to 1.03), more often had symptom onset between 00:00 and 05:59 a.m. (OR 1.86, 95% CI 1.10 to 3.12) and more often sought assistance from a general practitioner (OR 2.58, 95% CI 1.66 to 4.04) or attended the emergency room (OR 4.10, 95% CI 2.04 to 8.32). Sweats and considering the situation to be severe were factors associated with a reduced delay. After awareness campaigns, there was no change in patient delay, but the proportion of patients calling the Emergency Medical Services increased from 55% to 62% (P

BACKGROUND: Primary percutaneous coronary intervention (pPCI) is recommended in patients presenting with ST-elevation myocardial infarction (STEMI) within METHOD: Patients older than 18 years with first time STEMI referred to pPCI were eligible. cTnT and copeptin values were measured at admission. A cardiac magnetic resonance scanning (CMR) was done during the index admission for assessment of area at risk (AAR), and later 3 months to assess final infarct size (FIS). Myocardial salvage index (MSI) was calculated based on these measurements.RESULTS: A total of 468 patients were included. The median time from patient-reported onset of symptoms to pPCI was 192 min (IQR 150 min - 290 min). At presentation 416 (89%) patients had hs-cTnT values above the 99th percentile, median hs-cTnT was 53 ng/l (IQR 24 ng/l-146 ng/l) and 318 (68%) patients had copeptin values above the 99th percentile (18.9 pmol/l), median copeptin was 50 pmol/l (IQR 14 pmol/l-131 pmol/l). Symptom duration showed a weak but significant association with AAR (R 2 = 0.02, p = .04), FIS (R 2 = 0.03, p CONCLUSION: Copeptin/troponin-ratio is associated with patient-reported symptom duration, but there was no association with area at risk, final infarct size or myocardial salvage index.

Primary percutaneous intervention (PPCI) is the preferred treatment in patients with ST elevation myocardial infarction (STEMI) if this can be performed in a timely manner. The 2012 ESC Guidelines on management of AMI in patients presenting with ST-segment elevation advice that PPCI should be performed within 120 min of first medical contact. Prehospital diagnosis of patients with STEMI is performed to save time and make PPCI available to the majority of patients. Although diagnosing patients with STEMI is usually easy, there are important pitfalls and patients with STEMI are missed on occasion. In addition, it is well know that patients without ST elevation may also have a high-risk cardiac condition. The 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation stress the importance of urgent CAG in patients with high-risk non ST-segment elevation myocardial infarction (NSTEMI). Unfortunately, these patients are difficult to diagnose in the acute phase and important time may be spend establishing the correct diagnosis. Prehospital biomarker measurement has emerged as a method to gain important additional information. We review the evidence on prehospital diagnosis of patients with STEMI and, In addition, we present the current knowledge on the new diagnostic methods that could have a future role in prehospital rule-in and rule-out of cardiac disease.

Background Early withdrawal of recommended antiplatelet treatment with clopidogrel adversely affects prognosis following percutaneous coronary interventions. Optimal antiplatelet treatment is essential following ST ‐segment elevation myocardial infarction ( STEMI ) given the increased risk of thrombotic complications. This study assessed the frequency, predictors, and clinical impact of early prasugrel cessation in patients with STEMI undergoing primary percutaneous coronary interventions. Methods and Results We pooled patients with STEMI discharged on prasugrel in 2 prospective registries (Bern PCI Registry [ NCT 02241291] and SPUM ‐ ACS (Inflammation and Acute Coronary Syndromes) [ NCT 01000701]) and 1 STEMI trial ( COMFORTABLE ‐ AMI (Comparison of Biomatrix Versus Gazelle in ST‐Elevation Myocardial Infarction) [ NCT 00962416]). Prasugrel treatment status at 1 year was categorized as no cessation; crossover to another P2Y 12 ‐inhibitor; physician‐recommended discontinuation; and disruption because of bleeding, side effects, or patient noncompliance. In time‐dependent analyses, we assessed the impact of prasugrel cessation on the primary end point, a composite of cardiac death, myocardial infarction, and stroke. Of all 1830 included patients (17% women, mean age 59 years), 83% were treated with new‐generation drug‐eluting stents. At 1 year, any prasugrel cessation had occurred in 13.8% of patients including crossover (7.2%), discontinuation (3.7%), and disruption (2.9%). Independent predictors of any prasugrel cessation included female sex, age, and history of cerebrovascular event. The primary end point occurred in 5.2% of patients and was more frequent following disruption (hazard ratio 3.04, 95% confidence interval,1.34–6.91; P =0.008), without significant impact of crossover or discontinuation. Consistent findings were observed for all‐cause death, myocardial infarction, and stent thrombosis following prasugrel disruption. Conclusions In this contemporary study of patients with STEMI , early prasugrel cessation was not uncommon and primarily involved change to another P2Y 12 ‐inhibitor. Disruption was the only type of early prasugrel cessation associated with statistically significant excess in ischemic risk within 1 year following primary percutaneous coronary interventions.

BACKGROUND: Terminal QRS distortion on the electrocardiogram (ECG) is a sign of severe ischemia in patients with STEMI and can be quantified by the Sclarovsky-Birnbaum Severity of Ischemia. Due to score complexity, it has not been applied in clinical practice. Automatic scoring of digitally recorded ECGs could facilitate clinical application. We aimed to develop an automatic algorithm for the severity of ischemia.METHODS: Development set: 50 STEMI ECGs were manually (Manual-score) and automatically (Auto-score) scored by our designed algorithm. The agreement between Manual- and Auto-score was assessed by kappa statistics. Test set: ECGs from 199 STEMI patients were assigned a severity grade (severe or non-severe ischemia) by the Auto-score. Infarct size estimated by median peak Troponin T (TnT) and Creatinine Kinase Myocardial Band (CKMB) was tested between the groups.RESULTS: The agreement between Manual- and Auto-score was 0.83 ((95% CI 0.55-1.00), p CONCLUSION: The automatic ECG algorithm for severity of ischemia in STEMI performs adequately for clinical use. Severe ischemia obtained by the Auto-score was associated with biomarker estimated larger infarct size.

Copyright © The Author(s). 2018, Background: We aimed to evaluate the impact of thrombus aspiration (TA) during primary percutaneous coronary intervention (P-PCI) in ‘real-world’ settings. Methods: We performed a retrospective study, using data from the National Registry of Interventional Cardiology (RNCI 2006–2012, Portugal) with ST-elevation myocardial infarction (STEMI) patients treated with P-PCI. The primary outcome, in-hospital mortality, was analysed through adjusted odds ratio (aOR) and 95% confidence intervals (95%CI). Results: We assessed data for 9458 STEMI patients that undergone P-PCI (35% treated with TA). The risk of in-hospital mortality with TA (aOR 0.93, 95%CI:0.54–1.60) was not significantly decreased. After matching patients through the propensity score, TA reduced significantly the risk of in-hospital mortality (OR 0.58, 95%CI:0.35–0.98; 3500 patients). Conclusions: The whole cohort data does not support the routine use of TA in P-PCI, but the results of the propensityscore matched cohort suggests that the use of selective TA may improve the short-term risks of STEMI.

Background Although some studies found improved coronary flow and myocardial salvage when stent implantation was deferred, the DANAMI-3–DEFER (Third DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction) did not show any improvement in clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) and deferred stenting. Objectives This study sought to evaluate the effect of deferred stent implantation on infarct size, myocardial salvage, and microvascular obstruction (MVO) in patients with STEMI. Methods In the present DANAMI-3 substudy, a total of 510 patients with STEMI were randomized to PCI with deferred versus immediate stent implantation. The patients underwent a cardiac magnetic resonance examination before discharge after the index procedure and again 3 months later. The primary endpoint was final infarct size. Results Deferred stenting did not reduce final infarct size (9% left ventricle [LV]; interquartile range [IQR]: 3% to 18% vs. 10% LV; IQR: 3% to 18%; p = 0.67). Similarly, deferred stenting was not associated with myocardial salvage index (66%; IQR: 50% to 89% vs. 67%; IQR: 49% to 88%; p = 0.80) or presence of MVO (43% vs. 42%; p = 0.78). In a post hoc analysis, stent length was the only subgroup of 7 that had an effect on outcome. In patients with a stent length ≥24 mm, deferred stenting reduced the final infarct size (6% LV; IQR: 2% to 18% vs. 13% LV; IQR: 7% to 23%; p = 0.006; and p for interaction = 0.005). Conclusions In the DANAMI-3–DEFER cardiac magnetic resonance substudy, routine deferred stenting did not reduce infarct size or MVO and did not increase myocardial salvage. These results do not support the use of routine deferred stenting in STEMI patients treated with primary PCI. (DANish Study of Optimal Acute Treatment of Patients With ST-elevation Myocardial Infarction [DANAMI-3]; NCT01435408)

BACKGROUND: Cohort studies have revealed an increased risk for ventricular fibrillation (VF) and sudden cardiac death (SCD) in patients with atrial fibrillation (AF). In this study, we hypothesized that single nucleotide polymorphisms (SNP) previously associated with AF may be associated with the risk of VF caused by first ST-segment elevation myocardial infarction (STEMI).METHODS: We investigated association of 24 AF-associated SNPs with VF in the prospectively assembled case-control study among first STEMI-patients of Danish ancestry.RESULTS: We included 257 cases (STEMI with VF) and 537 controls (STEMI without VF). The median age at index infarction was 60 years for the cases and 61 years for the controls (p = 0.100). Compared to the control group, the case group was more likely to be male (86% vs. 75%, p = 0.001), have a history of AF (7% vs. 2%, p = 0.006) or hypercholesterolemia (39% vs. 31%, p = 0.023), and a family history of sudden death (40% vs. 25%, p CONCLUSION: In this study, we found that the 24 AF-associated SNPs may not be involved in increasing the risk of VF. Larger VF cohorts and use of new next generation sequencing and epigenetic may in future identify additional AF and VF risk loci and improve our understanding of genetic pathways behind the two arrhythmias.

Background— Pathological early Q waves (QW) are associated with adverse outcomes in patients with ST-segment–elevation myocardial infarction (STEMI). Primary percutaneous coronary intervention (PCI) may therefore be less beneficial in patients with QW than in patients without QW. Myocardial salvage index and microvascular obstruction (MVO) are markers for reperfusion success. Thus, to clarify the benefit from primary PCI in STEMI patients with QW, we examined the association between baseline QW and myocardial salvage index and MVO in STEMI patients treated with primary PCI. Methods and Results— The ECG was assessed before primary PCI for the presence of QW (early) in 515 STEMI patients. The patients underwent a cardiac magnetic resonance imaging scan at day 1 (interquartile range [IQR], 1–1) and again at day 92 (IQR, 89–96). Early QW was observed in 108 (21%) patients and was related to smaller final myocardial salvage index (0.59 [IQR, 0.39–0.69] versus 0.65 [IQR, 0.46–0.84]; P P P =0.03) and MVO (β=0.18; P =0.001) after adjusting for potential confounders. Conclusions— Patients presenting with their first STEMI and early QW in the ECG had smaller myocardial salvage index and more extensive MVO than non-QW despite treatment within 12 hours after symptom onset. However, final myocardial salvage index in patients with QW was substantial, and patients with QW still benefit from primary PCI. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01435408.

Background— The impact of disease severity on the outcome after complete revascularization in patients with ST-segment–elevation myocardial infarction and multivessel disease is uncertain. The objective of this post hoc study was to evaluate the impact of number of diseased vessel, lesion location, and severity of the noninfarct-related stenosis on the effect of fractional flow reserve–guided complete revascularization. Methods and Results— In the DANAMI-3-PRIMULTI study (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization), we randomized 627 ST-segment–elevation myocardial infarction patients to fractional flow reserve–guided complete revascularization or infarct-related percutaneous coronary intervention only. In patients with 3-vessel disease, fractional flow reserve–guided complete revascularization reduced the primary end point (all-cause mortality, reinfarction, and ischemia-driven revascularization; hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.17–0.64; P =0.001), with no significant effect in patients with 2-vessel disease (HR, 0.77; 95% CI, 0.47–1.26; P =0.29; P for interaction =0.046). A similar effect was observed in patients with diameter stenosis ≥90% of noninfarct-related arteries (HR, 0.32; 95% CI, 0.18–0.62; P =0.001), but not in patients with less severe lesions (HR, 0.72; 95% CI, 0.44–1.19; P =0.21; P for interaction =0.06). The effect was most pronounced in patients with 3-vessel disease and noninfarct-related stenoses ≥90%, and in this subgroup, there was a nonsignificant reduction in the end point of mortality and reinfarction (HR, 0.32; 95% CI, 0.08–1.32; P =0.09). Proximal versus distal location did not influence the benefit from complete revascularization. Conclusions— The benefit from fractional flow reserve–guided complete revascularization in ST-segment–elevation myocardial infarction patients with multivessel disease was dependent on the presence of 3-vessel disease and noninfarct diameter stenosis ≥90% and was particularly pronounced in patients with both of these angiographic characteristics. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01960933.