Prognostic Value of Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes.

BACKGROUND: Severity and extent of coronary artery disease (CAD) assessed by invasive coronary angiography (ICA) guide treatment and may predict clinical outcome in patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). OBJECTIVES: This study tested the hypothesis that coronary computed tomography angiography (CTA) is equivalent to ICA for risk assessment in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial evaluated timing of treatment in relation to outcome in patients with NSTEACS and included a clinically blinded coronary CTA conducted prior to ICA. Severity of CAD was defined as obstructive (coronary stenosis ≥50%) or nonobstructive. Extent of CAD was defined as high risk (obstructive left main or proximal left anterior descending artery stenosis and/or multivessel disease) or non-high risk. The primary endpoint was a composite of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or heart failure. RESULTS: Coronary CTA and ICA were conducted in 978 patients. During a median follow-up time of 4.2 years (interquartile range: 2.7 to 5.5 years), the primary endpoint occurred in 208 patients (21.3%). The rate of the primary endpoint was up to 1.7-fold higher in patients with obstructive CAD compared with in patients with nonobstructive CAD as defined by coronary CTA (hazard ratio [HR]: 1.74; 95% confidence interval [CI]: 1.22 to 2.49; p = 0.002) or ICA (HR: 1.54; 95% CI: 1.13 to 2.11; p = 0.007). In patients with high-risk CAD, the rate of the primary endpoint was 1.5-fold higher compared with the rate in those with non-high-risk CAD as defined by coronary CTA (HR: 1.56; 95% CI: 1.18 to 2.07; p = 0.002). A similar trend was noted for ICA (HR: 1.28; 95% CI: 0.98 to 1.69; p = 0.07). CONCLUSIONS: Coronary CTA is equivalent to ICA for the assessment of long-term risk in patients with NSTEACS. (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes [VERDICT]; NCT02061891).

Coronary CT Angiography in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: In patients with non-ST-segment elevation acute coronary syndrome (NSTEACS), coronary pathology may range from structurally normal vessels to severe coronary artery disease. OBJECTIVES: The purpose of this study was to test if coronary computed tomography angiography (CTA) may be used to exclude coronary artery stenosis ≥50% in patients with NSTEACS. METHODS: The VERDICT (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography in Patients With Acute Coronary Syndromes) trial (NCT02061891) evaluated the outcome of patients with confirmed NSTEACS randomized 1:1 to very early (within 12 h) or standard (48 to 72 h) invasive coronary angiography (ICA). As an observational component of the trial, a clinically blinded coronary CTA was conducted prior to ICA in both groups. The primary endpoint was the ability of coronary CTA to rule out coronary artery stenosis (≥50% stenosis) in the entire population, expressed as the negative predictive value (NPV), using ICA as the reference standard. RESULTS: Coronary CTA was conducted in 1,023 patients-very early, 2.5 h (interquartile range [IQR]: 1.8 to 4.2 h), n = 583; and standard, 59.9 h (IQR: 38.9 to 86.7 h); n = 440 after the diagnosis of NSTEACS was made. A coronary stenosis ≥50% was found by coronary CTA in 68.9% and by ICA in 67.4% of the patients. Per-patient NPV of coronary CTA was 90.9% (95% confidence interval [CI]: 86.8% to 94.1%) and the positive predictive value, sensitivity, and specificity were 87.9% (95% CI: 85.3% to 90.1%), 96.5% (95% CI: 94.9% to 97.8%) and 72.4% (95% CI: 67.2% to 77.1%), respectively. NPV was not influenced by patient characteristics or clinical risk profile and was similar in the very early and the standard strategy group. CONCLUSIONS: Coronary CTA has a high diagnostic accuracy to rule out clinically significant coronary artery disease in patients with NSTEACS.

Characterisation of lesions undergoing ischaemia-driven revascularisation after complete revascularisation versus culprit lesion only in patients with STEMI and multivessel disease: a DANAMI-3-PRIMULTI substudy.

AIMS: Treatment of the infarct-related artery only (IRA only) in ST-segment elevation myocardial infarction (STEMI) is associated with a significantly higher rate of ischaemia-driven revascularisation (ID-RV) during follow-up than fractional flow reserve-guided complete revascularisation (FFR-CRV). This study aimed to characterise all lesions which underwent ID-RV in the DANAMI-3-PRIMULTI trial with respect to location, stenosis grade and functional significance. METHODS AND RESULTS: The study included 627 patients with STEMI and multivessel disease; 313 patients were randomised to treatment of the IRA only versus 314 undergoing staged FFR-CRV during the index admission. Rates of admission for suspected cardiac ischaemia (17%) were similar in both groups; however, ID-RV was significantly less frequent in the FFR-CRV group than in the IRA-only group (5% vs. 17%; p<0.001). In both groups, the primary reason for ID-RV was related to non-culprit, non-treated lesions (N=71/82 lesions in IRA-only; N=13/26 in FFR-CRV). De novo lesions or revascularisation of previously treated lesions were rarely causes of ID-RV. In the IRA-only group, there was a trend towards a higher ID-RV rate for lesions with a higher stenosis grade and located in more proximal segments - in particular, ≥80% stenosis of the left anterior descending and right coronary artery also led to angina class IV/unstable angina. In the FFR-CRV group, an FFR value ≤0.80 was shown to be an appropriate threshold for revascularisation. CONCLUSIONS: FFR-CRV in STEMI is associated with a significantly lower rate of ID-RV at follow-up than treatment of the IRA only. This is due to a difference in non-culprit, non-treated lesions between both groups and not in de novo lesions or repeat revascularisation of previously treated lesions. Further considerations are warranted in case of high-grade non-culprit stenosis at proximal coronary segments, borderline FFR values and/or anticipated complex PCI.

Early Versus Standard Care Invasive Examination and Treatment of Patients With Non-ST-Segment Elevation Acute Coronary Syndrome.

BACKGROUND: The optimal timing of invasive coronary angiography (ICA) and revascularization in patients with non-ST-segment elevation acute coronary syndrome is not well defined. We tested the hypothesis that a strategy of very early ICA and possible revascularization within 12 hours of diagnosis is superior to an invasive strategy performed within 48 to 72 hours in terms of clinical outcomes. METHODS: Patients admitted with clinical suspicion of non-ST-segment elevation acute coronary syndrome in the Capital Region of Copenhagen, Denmark, were screened for inclusion in the VERDICT trial (Very Early Versus Deferred Invasive Evaluation Using Computerized Tomography) ( ClinicalTrials.gov NCT02061891). Patients with ECG changes indicating new ischemia or elevated troponin, in whom ICA was clinically indicated and deemed logistically feasible within 12 hours, were randomized 1:1 to ICA within 12 hours or standard invasive care within 48 to 72 hours. The primary end point was a combination of all-cause death, nonfatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia, or hospital admission for heart failure. RESULTS: A total of 2147 patients were randomized; 1075 patients allocated to very early invasive evaluation had ICA performed at a median of 4.7 hours after randomization, whereas 1072 patients assigned to standard invasive care had ICA performed 61.6 hours after randomization. Among patients with significant coronary artery disease identified by ICA, coronary revascularization was performed in 88.4% (very early ICA) and 83.1% (standard invasive care). Within a median follow-up time of 4.3 (interquartile range, 4.1-4.4) years, the primary end point occurred in 296 (27.5%) of participants in the very early ICA group and 316 (29.5%) in the standard care group (hazard ratio, 0.92; 95% CI, 0.78-1.08). Among patients with a GRACE risk score (Global Registry of Acute Coronary Events) >140, a very early invasive treatment strategy improved the primary outcome compared with the standard invasive treatment (hazard ratio, 0.81; 95% CI, 0.67-1.01; P value for interaction=0.023). CONCLUSIONS: A strategy of very early invasive coronary evaluation does not improve overall long-term clinical outcome compared with an invasive strategy conducted within 2 to 3 days in patients with non-ST-segment elevation acute coronary syndrome. However, in patients with the highest risk, very early invasive therapy improves long-term outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02061891.

Danegaptide for primary percutaneous coronary intervention in acute myocardial infarction patients: a phase 2 randomised clinical trial.

OBJECTIVES: Reperfusion immediately after reopening of the infarct-related artery in ST-segment elevation myocardial infarction (STEMI) may cause myocardial damage in addition to the ischaemic insult (reperfusion injury). The gap junction modulating peptide danegaptide has in animal models reduced this injury. We evaluated the effect of danegaptide on myocardial salvage in patients with STEMI. METHODS: In addition to primary percutaneous coronary intervention in STEMI patients with thrombolysis in myocardial infarction flow 0-1, single vessel disease and ischaemia time less than 6 hours, we tested, in a clinical proof-of-concept study, the therapeutic potential of danegaptide at two-dose levels. Primary outcome was myocardial salvage evaluated by cardiac MRI after 3 months. RESULTS: From November 2013 to August 2015, a total of 585 patients were randomly enrolled in the trial. Imaging criteria were fulfilled for 79 (high dose), 80 (low dose) and 84 (placebo) patients eligible for the per-protocol analysis. Danegaptide did not affect the myocardial salvage index (danegaptide high (63.9±14.9), danegaptide low (65.6±15.6) and control (66.7±11.7), P=0.40), final infarct size (danegaptide high (19.6±11.4 g), danegaptide low (18.6±9.6 g) and control (21.4±15.0 g), P=0.88) or left ventricular ejection fraction (danegaptide high (53.9%±9.5%), danegaptide low (52.7%±10.3%) and control (52.1%±10.9%), P=0.64). There was no difference between groups with regard to clinical outcome. CONCLUSIONS: Administration of danegaptide to patients with STEMI did not improve myocardial salvage. TRIAL REGISTRATION NUMBER: NCT01977755; Pre-results.

Myocardial Damage in Patients With Deferred Stenting After STEMI: A DANAMI-3-DEFER Substudy.

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).

Fractional Flow Reserve-Guided Complete Revascularization Improves the Prognosis in Patients With ST-Segment-Elevation Myocardial Infarction and Severe Nonculprit Disease: A DANAMI 3-PRIMULTI Substudy (Primary PCI in Patients With ST-Elevation Myocardial Infarction and Multivessel Disease: Treatment of Culprit Lesion Only or Complete Revascularization).

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.

Effect of Ischemic Postconditioning During Primary Percutaneous Coronary Intervention for Patients With ST-Segment Elevation Myocardial Infarction: A Randomized Clinical Trial.

Importance: Ischemic postconditioning of the heart during primary percutaneous coronary intervention (PCI) induced by repetitive interruptions of blood flow to the ischemic myocardial region immediately after reopening of the infarct-related artery may limit myocardial damage. Objective: To determine whether ischemic postconditioning can improve the clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, And Participants: In this multicenter, randomized clinical trial, patients with onset of symptoms within 12 hours, STEMI, and thrombolysis in myocardial infarction (TIMI) grade 0-1 flow in the infarct-related artery at arrival were randomized to conventional PCI or postconditioning. Inclusion began on March 21, 2011, through February 2, 2014, and follow-up was completed on February 2, 2016. Analysis was based on intention to treat. Interventions: Patients were randomly allocated 1:1 to conventional primary PCI, including stent implantation, or postconditioning performed as 4 repeated 30-second balloon occlusions followed by 30 seconds of reperfusion immediately after opening of the infarct-related artery and before stent implantation. Main Outcome and Measures: A combination of all-cause death and hospitalization for heart failure. Results: During the inclusion period, 1234 patients (975 men [79.0%] and 259 women [21.0%]; mean [SD] age, 62 [11] years) underwent randomization in the trial. Median follow-up was 38 months (interquartile range, 24-58 months). The primary outcome occurred in 69 patients (11.2%) who underwent conventional primary PCI and in 65 (10.5%) who underwent postconditioning (hazard ratio, 0.93; 95% CI, 0.66-1.30; P = .66). The hazard ratios were 0.75 (95% CI, 0.49-1.14; P = .18) for all-cause death and 0.99 (95% CI, 0.60-1.64; P = .96) for heart failure. Conclusions and Relevance: Routine ischemic postconditioning during primary PCI failed to reduce the composite outcome of death from any cause and hospitalization for heart failure in patients with STEMI and TIMI grade 0-1 flow at arrival. Trial Registration: clinicaltrials.gov Identifier: NCT01435408.

A cardiac catheterisation laboratory core curriculum for the continuing professional development of nurses and allied health professions: developed by the Education working group of the Nurses and Allied Professions Committee for the European Association of Percutaneous Cardiovascular Interventions (EAPCI) 2016.

AIMS: The aim of this report is to provide a standard educational structure for nurses and allied professionals (NAP) specialising in interventional cardiology. The curriculum can also be used as a basis for training on a certificate-based level in interventional cardiology. METHODS AND RESULTS: The curriculum was developed by a panel of experts from various allied health professions. The syllabus focuses on nine core areas of themes essential for NAP working in interventional cardiology. The highly technical knowledge required for working in interventional cardiology as well as the various roles of the different professional groups have been taken into consideration. CONCLUSIONS: This core curriculum will ensure that essential content is covered during education and a basic level of quality is achieved across specialty cardiovascular educational programmes throughout Europe.

Deferred versus conventional stent implantation in patients with ST-segment elevation myocardial infarction (DANAMI 3-DEFER): an open-label, randomised controlled trial.

BACKGROUND: Despite successful treatment of the culprit artery lesion by primary percutaneous coronary intervention (PCI) with stent implantation, thrombotic embolisation occurs in some cases, which impairs the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). We aimed to assess the clinical outcomes of deferred stent implantation versus standard PCI in patients with STEMI. METHODS: We did this open-label, randomised controlled trial at four primary PCI centres in Denmark. Eligible patients (aged >18 years) had acute onset symptoms lasting 12 h or less, and ST-segment elevation of 0·1 mV or more in at least two or more contiguous electrocardiographic leads or newly developed left bundle branch block. Patients were randomly assigned (1:1), via an electronic web-based system with permuted block sizes of two to six, to receive either standard primary PCI with immediate stent implantation or deferred stent implantation 48 h after the index procedure if a stabilised flow could be obtained in the infarct-related artery. The primary endpoint was a composite of all-cause mortality, hospital admission for heart failure, recurrent infarction, and any unplanned revascularisation of the target vessel within 2 years' follow-up. Patients, investigators, and treating clinicians were not masked to treatment allocation. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01435408. FINDINGS: Between March 1, 2011, and Feb 28, 2014, we randomly assigned 1215 patients to receive either standard PCI (n=612) or deferred stent implantation (n=603). Median follow-up time was 42 months (IQR 33-49). Events comprising the primary endpoint occurred in 109 (18%) patients who had standard PCI and in 105 (17%) patients who had deferred stent implantation (hazard ratio 0·99, 95% CI 0·76-1·29; p=0·92). Procedure-related myocardial infarction, bleeding requiring transfusion or surgery, contrast-induced nephopathy, or stroke occurred in 28 (5%) patients in the conventional PCI group versus 27 (4%) patients in the deferred stent implantation group, with no significant differences between groups. INTERPRETATION: In patients with STEMI, routine deferred stent implantation did not reduce the occurrence of death, heart failure, myocardial infarction, or repeat revascularisation compared with conventional PCI. Results from ongoing randomised trials might shed further light on the concept of deferred stenting in this patient population. FUNDING: Danish Agency for Science, Technology and Innovation, and Danish Council for Strategic Research.

Comparison of Outcome of Patients With ST-Segment Elevation Myocardial Infarction and Complete Versus Incomplete ST-Resolution Before Primary Percutaneous Coronary Intervention.

Some patients presenting with ST-segment elevation myocardial infarction (STEMI) have complete ST resolution in the electrocardiogram, which may be clinical useful in the triage of patients with STEMI. However, the importance of complete ST resolution in these patients remains uncertain. Thus, the purpose was to describe the prognosis of patients with complete ST resolution before primary percutaneous coronary intervention (PCI). Continuous ST monitoring from arrival until 90 minutes after PCI was performed in 933 patients with STEMI. Complete ST resolution was defined as no residual significant ST elevations before intervention. The patients were followed clinically for 5.5 years (range 0 to 6.8 years). Infarct size and myocardial salvage were assessed in a subgroup of patients (n = 221) by cardiovascular magnetic resonance. Complete ST resolution was observed in 24% of the patients, who had a higher incidence of Thrombolysis In Myocardial Infarction grade 2/3 flow before intervention (64% vs 24%), smaller infarct size (6% vs 11%), and higher myocardial salvage index (0.82 vs 0.69; all p <0.001) compared with patients with continuous ST elevations. Complete ST resolution was associated with a significantly lower rate of the composite end point of all-cause death and admission for heart failure (14% vs 22%; p = 0.006) although it only tended to be an independent predictor in a multivariate analysis (hazard ratio 0.69, 95% CI 0.49 to 1.06; p = 0.09). In conclusion, compared to patients without incomplete ST resolution, patients with STEMI and complete ST resolution before primary PCI have a higher incidence of normalized epicardial flow before PCI, a larger myocardial salvage and smaller infarct size after the procedure and presumably improved long-term outcome compared with incomplete ST resolution.

Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3­PRIMULTI): an open-label, randomised controlled trial.

BACKGROUND: Patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel coronary disease have a worse prognosis compared with individuals with single-vessel disease. We aimed to study the clinical outcome of patients with STEMI treated with fractional flow reserve (FFR)-guided complete revascularisation versus treatment of the infarct-related artery only. METHODS: We undertook an open-label, randomised controlled trial at two university hospitals in Denmark. Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful percutaneous coronary intervention (PCI) of the infarct-related artery, patients were randomly allocated (in a 1:1 ratio) either no further invasive treatment or complete FFR-guided revascularisation before discharge. Randomisation was done electronically via a web-based system in permuted blocks of varying size by the clinician who did the primary PCI. All patients received best medical treatment. The primary endpoint was a composite of all-cause mortality, non-fatal reinfarction, and ischaemia-driven revascularization of lesions in non-infarct-related arteries and was assessed when the last enrolled patient had been followed up for 1 year. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01960933. FINDINGS: From March, 2011, to February, 2014, we enrolled 627 patients to the trial; 313 were allocated no further invasive treatment after primary PCI of the infarct-related artery only and 314 were assigned complete revascularization guided by FFR values. Median follow-up was 27 months (range 12­44 months). Events comprising the primary endpoint were recorded in 68 (22%) patients who had PCI of the infarct-related artery only and in 40 (13%) patients who had complete revascularisation (hazard ratio 0∙56, 95% CI 0∙38­0∙83; p=0∙004). INTERPRETATION: In patients with STEMI and multivessel disease, complete revascularisation guided by FFR measurements significantly reduces the risk of future events compared with no further invasive intervention after primary PCI. This effect is driven by significantly fewer repeat revascularisations, because all-cause mortality and non-fatal reinfarction did not differ between groups. Thus, to avoid repeat revascularisation, patients can safely have all their lesions treated during the index admission. Future studies should clarify whether complete revascularization should be done acutely during the index procedure or at later time and whether it has an effect on hard endpoints. FUNDING: Danish Agency for Science, Technology and Innovation and Danish Council for Strategic Research.

The Third DANish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction: Ischemic postconditioning or deferred stent implantation versus conventional primary angioplasty and complete revascularization versus treatment of culprit lesion only: Rationale and design of the DANAMI 3 trial program.

BACKGROUND: In patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction, ischemic postconditioning has been shown to reduce infarct size, but the effect on clinical outcome has not been tested in a large randomized trial. In addition, deferring stent implantation in the infarct-related lesion 1 to 3 days after acute opening of the infarct-related artery could have protective effects, by reducing the risk of injury caused by distal embolization and microvascular obstruction. Finally, a considerable fraction of patients present with lesions in other coronary artery branches than the infarct-related artery. Whether a strategy of complete or partial revascularization of these patients should be preferred remains uncertain. STUDY DESIGN: The DANAMI 3 trial program was designed to investigate 3 different randomized treatment strategies in patients with ST-segment elevation myocardial infarction: (1) ischemic postconditioning versus conventional treatment with a primary end point of death and hospitalization for heart failure; (2) deferring stent implantation in the infarct-related lesion versus conventional treatment with a primary end point of death, hospitalization for heart failure, reinfarction, and repeat revascularization; and (3) treatment of the culprit lesion only versus fractional flow reserve-guided complete revascularization in patients with multivessel disease, with a primary end point of death, reinfarction, and repeat revascularization. SUMMARY: The DANAMI 3 trial program will determine whether either of 2 approaches to reduce reperfusion injury and distal microvascular obstruction with postconditioning or deferred stent implantation will translate into improved clinical outcome and whether patients with multivessel disease undergoing primary percutaneous coronary intervention will benefit from a strategy of complete or partial revascularization.

The impact of distal embolization and distal protection on long-term outcome in patients with ST elevation myocardial infarction randomized to primary percutaneous coronary intervention--results from a randomized study.

OBJECTIVES: The impact of angiographically visible distal embolization (DE) and distal protection occurring during primary percutaneous coronary intervention (PCI) on long-term outcome has not been studied in a contemporary ST-segment elevation myocardial infarction (STEMI) cohort. To evaluate the association between DE and long-term outcome in STEMI patients treated with primary PCI with or without distal protection. METHODS AND RESULTS: In this post-hoc analysis of a randomized study, 591 STEMI patients were randomized to conventional primary PCI or primary PCI with distal protection and followed for 5 years. There was no statistically significant difference in MACE rate between patients treated with or wthout distal protection (19% versus 25%; p=0.10). There seemed to be interaction between distal protection and DE in major adverse cardiac events (MACE) (p=0.08), mortality (p=0.02) and reinfarction (p=0.06), but not admission for heart failure (p=0.40). DE was related to increased risk of admission for heart failure independently of distal protection (12.0% versus 5.0; p=0.015). The MACE rate for patients treated with standard PCI with DE was 31.3% compared to 24.8% for patients without DE (p=0.30), and 44.4% for patients treated with distal protection with DE compared to 17.9% for patients without DE (p=0.005). DE was not related to mortality (p=0.52) or reinfarction (p=0.52) among patients treated with standard PCI, but was related to higher rates of mortality (p=0.012) and reinfarction (p=0.008) when distal protection was used. CONCLUSION: DE occurred in 11% of STEMI patients treated with conventional primary PCI, and was associated with increased risk of development of heart failure. Distal protection did not improve the 5-years MACE rate, and might even aggravate the prognosis following DE, but this should only be considered hypothesis-generating.

ST peak during percutaneous coronary intervention serves as an early prognostic predictor in patients with ST-segment elevation myocardial.

AIMS: To evaluate the clinical importance of the ST peak phenomenon during primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: Continuous ST monitoring was performed in 942 STEMI patients from arrival until 90 minutes after revascularisation. ST peak was defined as ≥1 mm increase in the ST-segment during PCI compared with the ST elevation before intervention. ST peak was observed in 26.9% of patients. During median follow-up of 4.1 years, 20.7% of patients experienced a major adverse cardiac event (MACE). ST peak was associated with higher rates of mortality (13.4% versus 9.3%; p=0.044), admission for heart failure (10.6% versus 5.2%; p=0.002) and MACE (26.9% versus 18.2%; p=0.002), but not reinfarction (7.1% versus 5.2%; p=0.14). In two different Cox regression analyses, adjusting for predictors of MACE and ST peak including ST resolution and epicardial flow, ST peak remained significantly associated with MACE: adjusted hazard ratio (HR) 1.40 (95% confidence interval [CI] 1.01-1.95) and 1.41 (95% CI: 1.02-1.96). CONCLUSIONS: In the largest study hitherto evaluating the ST peak phenomenon during primary PCI, we demonstrated that ST peak is a strong predictor of adverse long-term outcome and provides independent prognostic information beyond that provided by ST resolution and epicardial flow.

Long-term outcome after drug-eluting versus bare-metal stent implantation in patients with ST-segment elevation myocardial infarction: 5 years follow-up from the randomized DEDICATION trial (Drug Elution and Distal Protection in Acute Myocardial Infarction).

OBJECTIVES: This study sought to compare the long-term effects of drug-eluting stent (DES) compared with bare-metal stent (BMS) implantation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention. BACKGROUND: The randomized DEDICATION (Drug Elution and Distal Protection in Acute Myocardial Infarction) trial evaluated the outcome after DES compared with BMS implantation in patients with STEMI undergoing primary percutaneous coronary intervention. METHODS: Patients with a high-grade stenosis/occlusion of a native coronary artery presenting with symptoms <12 h and ST-segment elevation were enrolled after giving informed consent. Patients were randomly assigned to receive a DES or a BMS in the infarct-related lesion. Patients were followed for at least 5 years, and clinical endpoints were evaluated from population registries and hospital charts. The main endpoint was the occurrence of the first major adverse cardiac event (MACE), defined as cardiac death, nonfatal recurrent myocardial infarction, and target lesion revascularization. RESULTS: Complete clinical status was available in 623 patients (99.5%) at 5 years follow-up. The combined MACE rate was insignificantly lower in the DES group (16.9% vs. 23%), mainly driven by a lower need of repeat revascularization (p = 0.07). Whereas the number of deaths from all causes tended to be higher in the DES group (16.3% vs. 12.1%, p = 0.17), cardiac mortality was significantly higher (7.7% vs. 3.2%, p = 0.02). The 5-year stent thrombosis rates were generally low and similar between the DES and the BMS groups. No cardiac deaths occurring within 1 month could be clearly ascribed to stent thrombosis, whereas stent thrombosis was involved in 78% of later-occurring deaths. CONCLUSIONS: The 5-year MACE rate was insignificantly different, but the cardiac mortality was higher after DES versus BMS implantation in patients with STEMI. Stent thrombosis was the main cause of late cardiac deaths.

Deferred stent implantation in patients with ST-segment elevation myocardial infarction: a pilot study.

AIMS: Disturbance in the flow of an infarct-related artery due to embolisation of thrombus and plaque material occurs frequently during primary percutaneous coronary intervention (PCI) and is associated with impaired prognosis. The aim of the present study was to minimise the risk of embolisation during PCI in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: Of 124 consecutive patients with STEMI, thrombectomy and/or balloon dilatation was performed in 110 (89%). Stent implantation was deferred in 113 (91%) patients who then comprised the study group. In 38% of the patients stent implantation was deemed unnecessary at the second examination because of <30% residual stenosis and no visible thrombus, and all lesions re-examined three months later were patent. Major adverse cardiac events occurred in two patients during eight months of follow-up (one cardiac death, one case of reinfarction with target lesion revascularisation). In five patients no PCI was performed at all. Myocardial salvage determined by cardiac magnetic resonance in a subset of patients was relatively high. CONCLUSIONS: Deferred stent implantation is safe in the majority of patients with STEMI. Although the concept has to be evaluated in a randomised trial, the strategy may prove beneficial for many patients referred for primary PCI.

Usefulness of preprocedure high-sensitivity C-reactive protein to predict death, recurrent myocardial infarction, and stent thrombosis according to stent type in patients with ST-segment elevation myocardial infarction randomized to bare metal or drug-eluting stenting during primary percutaneous coronary intervention.

It is unknown whether high-sensitivity C-reactive protein (hs-CRP) predicts outcome depending on implanted stent type. We investigated the prognostic value of hs-CRP in relation to type of stent implanted in patients with ST-segment elevation myocardial infarction (STEMI). Immediately before primary percutaneous coronary intervention (pPCI), 301 patients had blood drawn. Patients were categorized according to hs-CRP levels and combination of hs-CRP (≤2 vs >2 mg/L) and stent type (bare metal stent [BMS] vs drug-eluting stent [DES]). Hs-CRP >2 mg/L (median, hazard ratio 2.7, 95% confidence interval 1.3 to 5.6, p = 0.007) and the combined variable of hs-CRP >2 mg/L and BMS (hazard ratio 2.4, 95% confidence interval 1.2 to 4.5, p = 0.006) independently predicted the composite end point of death and MI at 36-month follow-up. There was a significant interaction (p = 0.006) for hs-CRP and stent type. Survival analysis demonstrated significant differences for occurrence of death and MI: 4.8% in BMS + CRP ≤2 mg/L, 11.9% in DES + CRP ≤2 mg/L, 17.6% in DES + CRP >2 mg/L, and 27.9% in BMS + CRP >2 mg/L. None of the 14 stent thromboses occurred in patients with BMS + CRP ≤2 mg/L. In conclusion, preprocedure hs-CRP predicts outcome after pPCI in patients with STEMI. Our hypothesis-generating data indicate that BMS implantation should be preferred when hs-CRP is ≤2 mg/L and DES when hs-CRP is >2 mg/L to decrease long-term adverse outcomes including stent thrombosis in patients with STEMI treated with pPCI. These findings need confirmation in larger randomized clinical trials.

Long-term outcome after drug-eluting versus bare-metal stent implantation in patients with ST-segment elevation myocardial infarction: 3-year follow-up of the randomized DEDICATION (Drug Elution and Distal Protection in Acute Myocardial Infarction) Trial.

OBJECTIVES: The purpose of this study was to compare long-term clinical outcomes after implantation of drug-eluting stents (DES) and bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The evidence of long-term efficacy and safety after implantation of DES in patients with complex lesions is scarce. METHODS: We randomly assigned 626 patients with STEMI referred within 12 h to have a DES or a BMS implanted in the infarct-related lesion with or without distal protection during primary percutaneous coronary intervention. RESULTS: At 3 years, target lesion revascularization was 6.1% in the DES group compared with 16.3% in the BMS group (p<0.001), and the rate of major adverse cardiac events was 11.5% versus 18.2%, respectively (p=0.02). Whereas all-cause mortality did not differ significantly, the rate of cardiac death was higher in the DES group, 6.1% versus 1.9% for the BMS group (p=0.01). The occurrence of reinfarction, stroke, and stent thrombosis was similar. CONCLUSIONS: Implantation of DES in patients with STEMI reduces the long-term rate of major adverse cardiac events compared with BMS, but patients with DES had a higher risk of cardiac death not attributed to myocardial infarction or stent thrombosis. (Drug Elution and Distal Protection During Percutaneous Coronary Intervention in ST Elevation Myocardial Infarction [DEDICATION]; NCT00192868)

Increased rate of stent thrombosis and target lesion revascularization after filter protection in primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: 15-month follow-up of the DEDICATION (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction) trial.

OBJECTIVES: The purpose of this study was to evaluate the long-term effects of distal protection during percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The use of distal filter protection during primary PCI increases procedure complexity and may influence lesion treatment and stent implantation. METHODS: The STEMI patients were assigned to distal protection (DP) (n = 312) or conventional treatment (CT) (n = 314). Clinical follow-up was performed after 1, 6, and 15 months, and angiographic follow-up after 8 months. All target lesion revascularizations (TLRs) were clinically driven. We report the pre-specified end points of stent thrombosis according to the criteria of the Academic Research Consortium, TLR, and reinfarction after 15 months. RESULTS: The total number of stent thrombosis was 11 in the DP group and 4 in the CT group (p = 0.06). The rate of definite stent thrombosis was significantly increased in the DP group as compared with the CT group, with 9 cases versus 1 (p = 0.01). Clinically driven TLRs (31 patients vs. 18 patients, p = 0.05) and clinically driven target vessel revascularizations (37 patients vs. 22 patients, p = 0.04) were more frequent in the DP group. CONCLUSIONS: In primary PCI for STEMI, the routine use of DP increased the incidence of stent thrombosis and clinically driven target lesion/vessel revascularization during 15 months of follow-up. (Drug Elution and Distal Protection in ST Elevation Myocardial Infarction Trial [DEDICATION]; NCT00192868).