Assessment of sub-clinical acute cellular rejection after heart transplantation: comparison of cardiac magnetic resonance imaging and endomyocardial biopsy.

OBJECTIVE: Comparing the diagnostic value of multi-sequential cardiac magnetic resonance imaging (CMR) with endomyocardial biopsy (EMB) for sub-clinical cardiac allograft rejection. METHODS: One hundred and forty-six examinations in 73 patients (mean age 53 ± 12 years, 58 men) were performed using a 1.5 Tesla system and compared to EMB. Examinations included a STIR (short tau inversion recovery) sequence for calculation of edema ratio (ER), a T1-weighted spin-echo sequence for assessment of global relative enhancement (gRE), and inversion-recovery sequences to visualize late gadolinium enhancement (LGE). Histological grade ≥1B was considered relevant rejection. RESULTS: One hundred and twenty-seven (127/146 = 87 %) EMBs demonstrated no or mild signs of rejection (grades ≤1A) and 19/146 (13 %) a relevant rejection (grade ≥1B). Sensitivity, specificity, positive predictive, and negative predictive values were as follows: ER: 63 %, 78 %, 30 %, and 93 %; gRE: 63 %, 70 %, 24 %, and 93 %; LGE: 68 %, 36 %, 13 %, and 87 %; with the combination of ER and gRE with at least one out of two positive: 84 %, 57 %, 23 %, and 96 %. ROC analysis revealed an area under the curve of 0.724 for ER and 0.659 for gRE. CONCLUSION: CMR parameters for myocarditis are useful to detect sub-clinical acute cellular rejection after heart transplantation. Comparable results to myocarditis can be achieved with a combination of parameters. KEY POINTS: • Magnetic resonance imaging is useful for the assessment of cardiac allograft rejection. • CMR has a high negative predictive value for exclusion of allograft rejection. • Diagnostic performance is not yet good enough to replace endomyocardial biopsy.

MR imaging-guided electrophysiological ablation studies in humans with passive catheter tracking: initial results.

PURPOSE: To assess if real-time magnetic resonance (MR) imaging-guided radiofrequency (RF) ablation for atrial flutter is feasible in patients. MATERIALS AND METHODS: The study complied with the Declaration of Helsinki and was approved by the local ethics committee. All patients were informed about the investigational nature of the procedures and provided written informed consent. Ten patients (six men; mean age ± standard deviation, 68 years ± 10) with symptomatic atrial flutter underwent isthmus ablation. In all patients, two MR imaging conditional steerable diagnostic and ablation catheters were inserted into the coronary sinus via femoral sheaths and into the right atrium with fluoroscopic guidance. The patients were then transferred to a 1.5-T whole-body MR imager for an ablation procedure, in which the catheters were manipulated by an electrophysiologist by using a commercially available interactive real-time steady-state free precession MR imaging sequence. RESULTS: All catheters were placed in standard positions successfully. Furthermore, simple programmed stimulation maneuvers were performed. In one of 10 patients, a complete conduction block was performed with MR imaging guidance. In nine of 10 patients, creating only a small number of additional touch-up lesions was necessary to complete the isthmus block with conventional fluoroscopy (median, three lesions; interquartile range, two to four lesions). CONCLUSION: Real-time MR imaging-guided placement of multiple catheters is feasible in patients, with subsequent performance of stimulation maneuvers and occasional complete isthmus ablation.

Growth-differentiation factor 15 as predictor of mortality in acute reperfused ST-elevation myocardial infarction: insights from cardiovascular magnetic resonance.

OBJECTIVE: Growth-differentiation factor 15 (GDF-15), a stress-responsive member of the transforming growth factor beta cytokine superfamily, has emerged as a biomarker of increased mortality in cardiovascular disease. However, the exact pathophysiological mechanisms of GDF-15 in the cardiovascular system and in acute ST-elevation myocardial infarction (STEMI) are not well defined. The aim of this study was to determine the relation between GDF-15 and myocardial damage assessed by cardiovascular magnetic resonance (CMR) imaging and to evaluate the prognostic value of GDF-15 in a high-risk STEMI population exclusively reperfused by primary angioplasty. DESIGN, SETTING, PATIENTS: GDF-15 concentrations were determined by an ELISA in 238 consecutive patients undergoing primary angioplasty in STEMI less than 12 h after symptom onset. Patients were categorised into two groups defined by the median GDF-15 value on admission. CMR was performed 3 days (IQR 2-4) after infarction for assessment of infarct size, myocardial salvage and microvascular obstruction. The primary clinical endpoint was mortality within 6 months after the index event. RESULTS: Elevated GDF-15 concentrations over and above the median on admission were a strong predictor of mortality (19 vs one death, p<0.001) and major adverse cardiac events (27 vs nine events, p=0.001) at 6 months follow-up. Myocardial salvage was an inverse multivariable predictor of GDF-15 concentrations. CONCLUSIONS: GDF-15 on admission is a strong predictor of mortality in patients with STEMI reperfused by primary angioplasty, which is associated with decreased myocardial salvage and subsequent adverse clinical outcome. Clinical trail registration number http://www.clinicaltrials.gov/ NCT00463749.

Prognostic significance and determinants of myocardial salvage assessed by cardiovascular magnetic resonance in acute reperfused myocardial infarction.

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).

Endothelin-1 release in acute myocardial infarction as a predictor of long-term prognosis and no-reflow assessed by contrast-enhanced magnetic resonance imaging.

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.

Impact of high-dose N-acetylcysteine versus placebo on contrast-induced nephropathy and myocardial reperfusion injury in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. The LIPSIA-N-ACC (Prospective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate PercutaneouS Coronary Intervention Acute Myocardial Infarction N-ACC) Trial.

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).