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.

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.

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.

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.

Drug-eluting versus bare metal stents in patients with st-segment-elevation myocardial infarction: eight-month follow-up in the Drug Elution and Distal Protection in Acute Myocardial Infarction (DEDICATION) trial.

BACKGROUND: Implantation of drug-eluting stents (DES) limits the rate of coronary restenosis in most patients with coronary artery disease, but data are scarce with regard to their use in patients with ST-segment-elevation myocardial infarction and in connection with distal protection of the microvascular perfusion during primary percutaneous coronary intervention. METHODS AND RESULTS: We randomly assigned 626 patients referred within 12 hours from symptom onset of an ST-elevation myocardial infarction to have a DES or a bare metal stent implanted in the infarct-related lesion with or without distal protection during primary percutaneous coronary intervention. Quantitative coronary angiography was performed during the index treatment and 8 months later. The primary end point was loss of the lumen diameter in the infarct-related lesion induced by neointimal proliferation. Patients were comparable with regard to baseline demographic and angiographic characteristics. The mean late lumen loss was significantly lower in patients treated with a DES (0.06 mm; SD, 0.66 mm) than in patients who had a bare metal stent implanted (0.47 mm; SD, 0.69 mm; P<0.001). The rate of the composite end point of cardiac death, recurrent myocardial infarction, and target lesion revascularization was 8.6% in the DES group versus 14.4% in the bare metal stent group (P=0.03). Cardiac death occurred in 4.2% and 1.6% of the patients (P=0.09) and stent thrombosis occurred in 2.0% and 2.6% (P=0.72), respectively. CONCLUSIONS: Implantation of DES improves the angiographic outcome and need for repeat revascularization without increasing the short-term risk of stent thrombosis but has a tendency to increase cardiac death in patients with ST-segment-elevation myocardial infarction.

Restenosis in coronary bare metal stents. Importance of time to follow-up: a comparison of coronary angiograms 6 months and 4 years after implantation.

OBJECTIVES: Angiographic late lumen loss measured 6 to 9 month after bare metal stent implantation in the coronary arteries is a validated restenosis parameter. DESIGN: We performed a second angiographic follow-up after 4 years in event free survivors from the DANSTENT trial cohort. RESULTS: Quantitative comparison of paired coronary angiograms at 6 months and 4 years showed a reduction of late loss from 0.68+/-0.52 mm to 0.42 (+/-0.52) (mean difference 0.26 (0.17 to 0.36), p<0.0001). Minimal instent lumen diameter had increased from 2.39+/-0.62 mm to 2.64+/-0.56 mm (mean difference: -0.24 mm, 95% confidence interval: -0.34 mm to -0.14 mm, p<0.0001). Instent diameter stenosis decreased from 24.8+/-14.2% to 18.6+/-9.3% (mean difference 6.16%, 95% confidence interval: 2.82 to 9.48%, p=0.0006). This observed spontaneous decrease of instent restenosis corresponds to a 19% increase of minimal cross-sectional vessel area and a 39% reduction of the binary restenosis rate over time. CONCLUSIONS: Instent late lumen loss in bare metal stents decreases spontaneously over time. Maturation of early hyperplastic tissue reaction after stent implantation with subsequent thinning of fibrotic tissue might explain this phenomenon.

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.

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.

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.

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.

Sirolimus versus bare metal stent implantation in patients with total coronary occlusions: subgroup analysis of the Stenting Coronary Arteries in Non-Stress/Benestent Disease (SCANDSTENT) trial.

BACKGROUND: Coronary restenosis is more common in a total coronary occlusion (TCO) than other lesion types after implantation of bare metal stents (BMS). But whereas sirolimus-eluting stents (SES) have been shown to improve the outcomes in simple coronary artery lesions, data on their efficacy in complex coronary lesions are scarce. METHODS: We enrolled 127 patients with coronary artery disease and a TCO > or = 15 mm in length to have either SES or BMS implanted after successful recanalization. Outcome measures included the minimal lumen diameter, the late lumen loss, and angiographic restenosis (> 50% diameter stenosis) at 6 months follow-up and the occurrence of target vessel failure during a 7-month period. RESULTS: The patients were well matched in demographic and angiographic baseline characteristics, and 20% had diabetes. The reference vessel was 2.92 mm in mean, and the lesion length was 25.2 mm. At follow-up, patients who received SES had a minimal lumen diameter of 2.49 mm compared with 1.46 mm in those who received BMS (P = .015), 0% versus 38% developed restenosis (P < .001), lumen loss was -0.05 versus 0.99 mm (P < .001), and the target vessel failure rate 5% with SES versus 35% with BMS (P < .001). Stent thrombosis occurred in 1 patient in the BMS group. CONCLUSIONS: Implantation of SES is safe, and it markedly reduces angiographic restenosis and the occurrence of adverse events in patients with a TCO.

Comparison of sirolimus-eluting and bare metal stents in coronary bifurcation lesions: subgroup analysis of the Stenting Coronary Arteries in Non-Stress/Benestent Disease Trial (SCANDSTENT).

BACKGROUND: Sirolimus-eluting stent implantation improves the outcome in simple coronary artery lesions compared with bare metal stents, but there is limited evidence of their safety and efficacy when implanted in complex lesions like coronary bifurcations. METHODS: SCANDSTENT was a randomized controlled study comparing implantation of sirolimus-eluting stents with bare-metal stents in patients with complex coronary artery disease. This substudy evaluates the angiographic and clinical outcome of 126 patients with lesions located in a coronary bifurcation. RESULTS: The baseline characteristics of the patients were comparable: 15% had diabetes, and 1.7 stents were implanted per lesion. At follow-up, the minimum lumen diameter of the main branch was 2.35 mm in patients who received sirolimus-eluting stents compared with 1.68 mm in those who received bare-metal stents, and that of the side branch was 1.70 versus 1.19 mm (both P < .001). The late lumen loss in the main branch was 0.12 mm in the sirolimus-eluting stent group versus 0.99 mm in the bare-metal stent group and 0.03 versus 0.56 mm in the side branch (both P < .001). Thus, sirolimus-eluting stents reduced the restenosis rate from 28.3% to 4.9% in the main branch and from 43.4% to 14.8% in the side branches (both P < .001). Major adverse cardiac events occurred in 9% with sirolimus-eluting stents versus 28% with bare-metal stents (P = .01), and stent thrombosis was observed in 0% versus 9% (P = .02). CONCLUSION: Sirolimus-eluting stent implantation improves both the angiographic and clinical outcomes considerably compared with that of bare-metal stents in patients with stenoses located in coronary bifurcations.

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.

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.

Low restenosis rate of the NIR coronary stent: results of the Danish multicenter stent study (DANSTENT)--a randomized trial comparing a first-generation stent with a second-generation stent.

BACKGROUND: Larger studies evaluating the angiographic results of second-generation stents are scarce. The objectives of this study were to assess current standards of angiographic and clinical outcomes after implantation of the second-generation stainless steel stent, NIR (Medinol Ltd, Tel Aviv, Israel), and to compare the outcomes with those of the first-generation Palmaz-Schatz (PS) stent (Johnson & Johnson, Warren, NJ). METHODS: Patients having coronary artery lesions that could be covered by a stent of 15 mm in length were randomly assigned to receive the NIR or the PS. Procedural success, 6-month angiographic findings, and 1-year clinical outcomes were determined. RESULTS: In 424 patients included in the study, the overall procedural success rate was high (NIR 98%, PS 99%, P =.90). Follow-up angiography was conducted in 91% of the patients. The overall rate of angiographic restenosis was low in both groups (NIR 9.9%, PS 12.6%, P =.35). We found a low restenosis rate in vessels with a minimal lumen diameter >3.1 mm after the procedure, particularly in the NIR group (<6%). The rate of target lesion revascularization after 1 year did not differ (NIR 12%, PS 10%, P =.47). CONCLUSIONS: The angiographic and clinical outcomes after implantation of the second-generation stainless steel stent were not significantly better than those of the first-generation stent. The low restenosis rates, particularly in patients with the largest minimal lumen diameters after stent implantation, warrants circumspection when planning the evaluation of newer stent technologies that aim to further reduce coronary restenosis.

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.