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Objective: In acute myocardial infarction, cardiovascular magnetic resonance (CMR) allows for quantifying the extent of salvaged myocardium after reperfusion as a potential strong end point for clinical trials. The aim of this study was to investigate whether the early prognostic significance of myocardial salvage assessed by CMR is sustained at long-term clinical follow-up in patients with ST-elevation myocardial infarction (STEMI) undergoing primary angioplasty., Design, Setting, Patients: We analysed 208 consecutive patients with STEMI undergoing primary angioplasty <12 h after symptom onset. T2-weighted and contrast-enhanced CMR was used to calculate the myocardial salvage index (MSI). Patients were categorised into two groups defined by the median MSI. The primary end point was the occurrence of major adverse cardiovascular events defined as death, reinfarction and new congestive heart failure at long-term follow-up., Results: The median MSI was 48 (IQR 27 to 73). Long-term follow-up was available in 202 patients (97%) at a median of 18.5 months (IQR 13.8 to 20.8). Major adverse cardiovascular events occurred in 33 patients (16%), with a significantly lower event rate in the MSI ≥ median group (7 vs 26 events, p<0.001). Mortality was significantly reduced in the MSI ≥ median group (2 vs 12 deaths, p = 0.001). MSI was a significant independent predictor for a favourable long-term survival on multivariable Cox regression analysis after adjustment for established prognostic markers., Conclusions: MSI assessed by CMR predicts long-term clinical outcome in acute reperfused STEMI. Therefore, our data support the use of myocardial salvage as an end point for clinical trials investigating novel reperfusion strategies. Trial registration number http://www.ClinicalTrials.gov: NCT00952224.

Background: Abciximab reduces major adverse cardiac events (MACEs) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Intracoronary (IC) abciximab bolus application might be more effective than a standard intravenous (IV) bolus. So far the occurrence of aborted MI, a new therapeutic target of effective treatment in STEMI, has not been evaluated in IC versus IV abciximab administration in STEMI patients undergoing primary PCI., Methods: To investigate the extent of aborted MI, 154 patients undergoing primary PCI were randomized to either IC (n=77) or IV (n=77) bolus abciximab administration with subsequent 12-hour intravenous infusion. For assessment of infarct size and extent of microvascular obstruction, all patients underwent late enhancement magnetic resonance imaging (MRI). Aborted MI was defined by major (≥ 50%) ST-segment resolution and a lack of subsequent cardiac enzyme rise ≥ 2 the upper normal limit. We also assessed the occurrence of true aborted MI defined as the absence of myocardial necrosis in MRI., Results: The incidence of aborted MI was significantly higher in the IC group (p=0.04); true aborted MI was only observed in the IC abciximab group (p=0.01). At multivariable logistic regression analysis, IC abciximab application was a significant independent predictor of true aborted MI (p=0.03). Aborted MI patients had an excellent prognosis at 6-month follow-up with no MACE as compared to 24 events in patients with non-aborted MI., Conclusions: IC bolus application of abciximab in STEMI patients undergoing primary PCI results in a higher incidence of aborted MI and subsequent improved clinical outcome., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: The aim of this study was to assess the effects of N-acetylcysteine (N-ACC) on contrast-induced nephropathy (CIN) defined by Cystatin C (Cys-C) serum levels and to evaluate the influence of Cys-C on clinical outcome in patients with ST-elevation myocardial infarction (STEMI)., Methods: In total, 251 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) were randomized to either high-dose N-ACC (2 × 1200 mg/d for 48 h) with optimal hydration or placebo plus optimal hydration. Serum Cys-C was measured at baseline, immediately, 24, 48 and 72 h after PCI. CIN was defined as an increase in serum Cys-C levels of 25% or more from baseline within 72 h after PCI. Major adverse cardiac events (MACE)--defined as death, recurrent infarction and congestive heart failure--within 6 months were recorded., Results: Baseline Cys-C was 1294 ± 611 and 1352 ± 811 ng/mL (p = 0.54) for the N-ACC and placebo group, respectively. There was a steady increase in Cys-C in both groups within the first 72 h after randomization. CIN occurred in 74.6 and in 70.4% of patients in the N-ACC and placebo group, respectively (p = 0.46). The magnitude of increase in the serum concentration of Cys-C was an independent predictor for MACE after 6 months of follow-up., Conclusions: High-dose N-ACC does not provide additional benefit over placebo with respect to Cys-C defined CIN in STEMI patients undergoing primary PCI. The magnitude of increase in Cys-C serum levels in the early course after STEMI is a predictor of medium-term MACE.

Cardiac magnetic resonance (CMR) offers a variety of parameters potentially suited as surrogate endpoints in clinical trials of acute myocardial infarction such as infarct size, myocardial salvage, microvascular obstruction or left ventricular volumes and ejection fraction. The present article reviews each of these parameters with regard to the pathophysiological basis, practical aspects, validity, reliability and its relative value (strengths and limitations) as compared to competitive modalities. Randomized controlled trials of acute myocardial infarction which have used CMR parameters as a primary endpoint are presented.

Objectives: The objective of this study was to assess the area at risk (AAR) in ST-segment elevation myocardial infarction with 2 different cardiac magnetic resonance (CMR) imaging methods and to compare them with the validated angiographic Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease Score (APPROACH-score) in a large consecutive patient cohort., Background: Edema imaging with T(2)-weighted CMR and the endocardial surface area (ESA) assessed by late gadolinium enhancement have been introduced as relatively new methods for AAR assessment in ST-segment elevation myocardial infarction. However, data on the utility and validation of these techniques are limited., Methods: A total of 197 patients undergoing primary percutaneous coronary intervention in acute ST-segment elevation myocardial infarction were included. AAR (assessed with T(2)-weighted edema imaging and the ESA method), infarct size, and myocardial salvage (AAR minus infarct size) were determined by CMR 2 to 4 days after primary angioplasty. Angiographic AAR scoring was performed by use of the APPROACH-score. All measurements were done offline by blinded observers., Results: The AAR assessed by T(2)-weighted imaging showed good correlation with the angiographic AAR (r = 0.87; p < 0.001), whereas the ESA showed only a moderate correlation either to T(2)-weighted imaging (r = 0.56; p < 0.001) or the APPROACH-score (r = 0.44; p < 0.001). Mean AAR by ESA (20.0 ± 11.7% of left ventricular mass) was significantly (p < 0.001) smaller than the AAR assessed by T(2)-weighted imaging (35.6 ± 10.9% of left ventricular mass) or the APPROACH-score (27.9 ± 10.5% of left ventricular mass) and showed a significant negative dependence on myocardial salvage index. In contrast, no dependence of T(2)-weighted edema imaging or the APPROACH-score on myocardial salvage index was seen., Conclusions: The AAR can be reliably assessed by T(2)-weighted CMR, whereas assessment of the AAR by ESA seems to be dependent on the degree of myocardial salvage, thereby underestimating the AAR in patients with high myocardial salvage such as aborted infarction. Thus, assessment of the AAR with the ESA method cannot be recommended. (Myocardial Salvage and Contrast Dye Induced Nephropathy Reduction by N-Acetylcystein [LIPSIA-N-ACC]; NCT00463749)., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Administration of abciximab during primary percutaneous coronary intervention (PCI) reduces major adverse cardiac events (MACE) in patients with ST-elevation myocardial infarction (STEMI). Intracoronary (IC) abciximab bolus application during PCI results in high local drug concentration, improved perfusion, reduction of infarct size, and less microvascular obstruction early after infarction. Aim of this study was to investigate whether the early benefits of an IC abciximab administration in STEMI patients undergoing PCI are sustained at 6 months., Methods: We performed 6-month follow-up of 154 STEMI patients undergoing PCI, who were randomised to either IC (n = 77) or intravenous (IV) (n = 77) bolus abciximab administration with subsequent 12-h intravenous infusion. The primary endpoint was infarct size at 6-month follow-up as assessed by delayed enhancement magnetic resonance imaging. Clinical end points were MACEs within 6 months after infarction., Results: The median infarct size after 6 months was significantly reduced in the IC abciximab group (16.7 vs. 24.1%, p = 0.002). A significant recovery of LV function was only observed in the IC abciximab group (p < 0.001), and IC abciximab group patients had significantly less adverse remodelling as compared to standard IV abciximab treatment (p = 0.03). These beneficial effects also translated into a strong trend towards a reduced MACE rate in the IC abciximab group at 6-month follow-up (10 vs. 21%, p = 0.07)., Conclusions: Intracoronary abciximab application in STEMI patients undergoing PCI is superior to standard IV treatment with respect to infarct size, recovery of LV function and reverse remodelling 6 months after infarction.

Aims: Early and late microvascular obstruction (MO) assessed by magnetic resonance imaging (MRI) are prognostic markers for combined clinical endpoints after ST-elevation myocardial infarction (STEMI). However, there are only limited data for hard endpoints and no consensus exists which of the two best predicts clinical outcome. Furthermore, it is unclear whether the assessment of MO by MRI adds incremental prognostic information independent of traditional outcome markers., Methods and Results: STEMI patients reperfused by primary angioplasty (n = 438) < 12 h after symptom onset underwent MRI at a median of 3 days after the index event. Microvascular obstruction was measured 1 and 15 min after gadolinium injection (early and late MO). Clinical follow-up was conducted after a median of 19 months. The primary endpoint was defined as a composite of death, non-fatal myocardial re-infarction, and congestive heart failure. In contrast to the presence and extent of early MO, the presence and extent of late MO were independently associated with the composite primary endpoint in the multivariable Cox regression analysis adjusting for post-percutaneous coronary intervention TIMI-flow, ST-resolution, TIMI-risk score, ejection fraction, and infarct size. The presence of late MO was identified as the strongest independent predictor for the occurrence of the composite endpoint (hazard ratio 4.23, 95%CI 1.73-10.34, P = 0.002). Furthermore, the presence and extent of late MO provided an incremental prognostic value above the traditional prognostic markers., Conclusion: In contrast to early MO, the presence and extent of late MO are strong independent prognosticators after STEMI. www.ClinicalTrials.gov: NCT00299377.

Objectives: The aim of the study was to determine the prognostic significance and determinants of myocardial salvage assessed by cardiovascular magnetic resonance (CMR) in reperfused ST-segment elevation myocardial infarction., Background: In acute myocardial infarction, CMR can retrospectively detect the myocardium at risk and the irreversible injury. This allows for quantifying the extent of salvaged myocardium after reperfusion as a potential strong end point for clinical trials and outcome., Methods: We analyzed 208 consecutive ST-segment elevation myocardial infarction patients undergoing primary angioplasty <12 h after symptom onset. T2-weighted and contrast-enhanced CMR was used to calculate the myocardial salvage index (MSI). Patients were categorized into 2 groups defined by the median MSI. The primary end point of the study was occurrence of major adverse cardiovascular events defined as death, reinfarction, and occurrence of new congestive heart failure within 6 months after the index event., Results: The median MSI was 48 (interquartile range 27 to 73). Major adverse cardiovascular events were significantly lower in the MSI >or= median group (2.9% vs. 22.1%, p < 0.001). The stepwise Cox proportional hazards model revealed that the MSI was the strongest predictor of major adverse cardiovascular events at 6-month follow-up (p < 0.001). All prognostic clinical (symptom onset to reperfusion), angiographic (Thrombolysis In Myocardial Infarction flow grade before angioplasty), and electrocardiographic (ST-segment resolution) parameters showed significant correlations with the MSI (p < 0.001 for all)., Conclusions: This study for the first time demonstrates that the MSI assessed by CMR predicts the outcome in acute reperfused ST-segment elevation myocardial infarction. Therefore, MSI assessment has important implications for patient prognosis as well as for the design of future trials intended to test new reperfusion therapy efficacy. (Myocardial Salvage Assessed by Cardiovascular Magnetic Resonance-Impact on Outcome; NCT00952224).

Objectives: The aim of this randomized, single-blind, controlled trial was to assess N-acetylcysteine effects on contrast-induced nephropathy and reperfusion injury in ST-segment elevation myocardial infarction patients undergoing primary angioplasty with moderate contrast volumes., Background: High-dose N-acetylcysteine reduced the incidence of contrast-induced nephropathy in patients with high contrast volumes and reduced reperfusion injury in animal trials., Methods: Patients undergoing primary angioplasty were randomized to either high-dose N-acetylcysteine (2 x 1,200 mg/day for 48 h; n = 126) or placebo plus optimal hydration (n = 125). The 2 primary end points were: 1) the occurrence of >25% increase in serum creatinine level <72 h after randomization; and 2) a reduction in reperfusion injury measured as myocardial salvage index by magnetic resonance imaging., Results: The median volume of an iso-osmolar contrast agent during angiography was 180 ml (interquartile range [IQR] 140 to 230 ml) in the N-acetylcysteine and 160 ml (IQR 120 to 220 ml) in the placebo group (p = 0.20). The primary end point contrast-induced nephropathy occurred in 14% of the N-acetylcysteine group and in 20% of the placebo group (p = 0.28). The myocardial salvage index was also not different between both treatment groups (43.5; IQR 25.4 to 71.9 vs. 51.5; IQR 29.5 to 75.3; p = 0.36). Activated oxygen protein products and oxidized low-density lipoprotein as markers for oxidative stress were reduced by as much as 20% in the N-acetylcysteine group (p < 0.05), whereas no change was evident in the placebo group., Conclusions: High-dose intravenous N-acetylcysteine reduces oxidative stress. However, it does not provide an additional clinical benefit to placebo with respect to CIN and myocardial reperfusion injury in nonselected patients undergoing angioplasty with moderate doses of contrast medium and optimal hydration. (Myocardial Salvage and Contrast Dye Induced Nephropathy Reduction by N-Acetylcysteine [LIPSIA-N-ACC]; NCT00463749).

Background: No-reflow after primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) is associated with poor prognosis. Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor that might aggravate reperfusion injury. The aim of our study was to assess the relationship between systemic ET-1 levels and the occurrence of no-reflow as well as to evaluate the prognostic value of ET-1 in a high-risk STEMI population., Methods: We examined 128 consecutive patients undergoing primary PCI in acute STEMI <12 hours after symptom onset. Endothelin-1 was assessed before and immediately after primary PCI. Patients were categorized into 2 groups defined by the median ET-1 level on admission. No-reflow was assessed by 3 different methods after PCI: angiographic Thrombolysis in Myocardial Infarction (TIMI) flow and myocardial blush grade, electrocardiographic ST-resolution, and microvascular obstruction (MO) measured by cardiac magnetic resonance imaging (MRI). The primary clinical end points were mortality and major adverse cardiovascular events. Clinical follow-up was conducted after a median of 19 months., Results: Patients with angiographically (TIMI flow < or =2 or TIMI flow 3 with final myocardial bush grade < or =2 after PCI), electrocardiographically (ST-resolution <30%), and MRI- (presence of MO) detected no-reflow had significantly higher ET-1 levels on admission. At multivariable logistic regression analysis, ET-1 levels on admission were the only significant predictor of MRI-detected no-reflow (P = .03) together with left ventricular ejection fraction (P = .002). An elevated ET-1 level > or = the median on admission was a significant predictor of long-term mortality., Conclusions: Endothelin-1 on admission is associated with no-reflow and increased long-term mortality in a high-risk STEMI population reperfused by primary PCI., (2010 Mosby, Inc. All rights reserved.)

The aim of this study was to determine whether angiographically visible collaterals before reperfusion are associated with beneficial effects on infarct size, microvascular obstruction, and left ventricular function as measured by magnetic resonance imaging (MRI) in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). We examined 235 patients with STEMI and symptoms <12 hours. All patients had Thrombolysis In Myocardial Infarction grade < or =1 flow before PCI. Collateral flow was graded according to Rentrop classification. Patients were divided in 2 groups; group A had absent or weak collateral flow and group B had significant flow. In 166 patients there was absent or weak collateral flow, whereas 69 had significant flow. Extent of microvascular obstruction was significantly smaller in group B at early MRI (3.3% vs 2.1% of left ventricle, p = 0.009). Infarct size measured by peak creatine kinase release showed smaller infarcts in group B (p = 0.02), whereas MRI infarct size showed a weak trend (p = 0.20). At 6 months, a strong trend toward a lower rate of death or nonfatal reinfarction could be seen in group B (4.5% vs 12.2%, p = 0.07). In conclusion, well-developed collaterals before reperfusion by PCI in patients with STEMI are associated with a protective effect on coronary microcirculation.

Background: Aborted myocardial infarction (MI) is defined by major (> or =50%) ST-segment resolution and a lack of subsequent cardiac enzyme rise > or =2 the upper normal limit. This ultimate myocardial salvage has been observed in approximately 15% of ST-elevation MI (STEMI) patients after fibrinolysis. So far, the prognostic significance and magnetic resonance imaging (MRI) findings of an aborted MI after primary angioplasty have not been evaluated appropriately., Methods: We examined 420 consecutive STEMI patients undergoing primary angioplasty within 12 hours after symptom onset. All patients underwent MRI within 1 to 4 days. Clinical end points were major adverse cardiovascular events within 6 months after the index event., Results: Of the 420 STEMI patients, 58 (14%) fulfilled aborted MI criteria. As compared with true MI, patients with aborted MI had a significant lower infarct size, shorter pain-to-balloon time, and better left ventricular ejection fraction (P < .001, respectively). Aborted MI patients had a 6-month major adverse cardiovascular event rate of 1.7% versus 19.6% of true MI patients (P = .001). In aborted MI patients, MRI detected no myocardial scar in 30 (56%), and a minor necrosis/scar formation in 24 patients (44%)., Conclusion: The proven prognostic relevance of aborted MI makes it a meaningful end point and therapeutic target in future MI studies. MRI can further distinguish between true aborted MI with absence of myocardial scar and aborted MI with scar formations.

The clinical role of magnetic resonance in diseases of the heart and great vessels is rapidly evolving. Cardiovascular magnetic resonance (CMR) has become an established non-invasive imaging modality for the assessment of various cardiac disorders, such as congenital heart disease, cardiac masses, cardiomyopathies, aortic and pericardial diseases. Moreover, due to its accuracy and reproducibility, CMR is currently considered the gold standard for quantification of ventricular volumes, function, and mass. Thus, this technique is ideally suited to assess the efficacy of therapeutic interventions on ventricular hypertrophy and remodelling, which may allow a reduction in sample size to show clinically relevant effects. Comprehensive functional assessment is possible by CMR due to its capability to measure flow velocity and flow volume, which is a basic requirement to quantify lesion severity in valvular heart disease. Within the past years, major technical advances have considerably improved acquisition speed and image quality making CMR a useful tool for the evaluation of patients with ischaemic heart disease. Although the clinical robustness of coronary magnetic resonance angiography still needs improvement, CMR currently provides valuable information to detect reversible ischemia, myocardial infarction, and residual viability. In this review we will present in detail the well-established indications of CMR accompanied by an outlook on new applications that are likely to enter the clinical arena in the near future.