Gert Klug

Prognostic Value of Microvascular Obstruction and Infarct Size, as Measured by CMR in STEMI Patients

The aim of this study was to evaluate the value of microvascular obstruction (MO) and infarct size as a percentage of left ventricular mass (IS%LV), as measured by contrast-enhanced cardiac magnetic resonance, in predicting major cardiovascular adverse events (MACE) at 2 years in patients with ST-segment elevation myocardial infarction reperfused by primary percutaneous coronary intervention. Individual data from 1,025 patients were entered into the pooled analysis. MO was associated with the occurrence of MACE, defined as a composite of cardiac death, congestive heart failure, and myocardial re-infarction (adjusted hazard ratio: 3.74; 95% confidence interval: 2.21 to 6.34). IS%LV ≥25% was not associated with MACE (adjusted hazard ratio: 0.90; 95% confidence interval: 0.59 to 1.37). The authors conclude that MO is an independent predictor of MACE and cardiac death, whereas IS%LV is not independently associated with MACE.

Predictive value of NT-pro BNP after acute myocardial infarction: Relation with acute and chronic infarct size and myocardial function

AIM OF THE STUDY We sought to assess the relation of N-terminal brain natriuretic peptide (NT-pro BNP) determined on day 3 after onset of acute myocardial infarction (AMI) symptoms with acute and chronic infarct size and functional parameters assessed by cardiac magnetic resonance (CMR) imaging. Furthermore, we wanted to investigate its predictive value for recovery of myocardial function. METHODS CMR was performed in 49 consecutive patients within 6 days and in a subgroup 4 (n = 27) and 12 (n = 22) months after first acute ST-elevation AMI and successful primary angioplasty. NT-pro BNP was measured in the subacute phase at 66 ± 8 h after onset of symptoms. RESULTS Log-transformed NT-pro BNP (lgNT-pro BNP) significantly correlated with infarct size in % of left ventricular myocardial mass (r = 0.59 to 0.64; p < 0.004), with ejection fraction (EF) (r = -0.49 to -0.55; p < 0.004) as well as with segmental wall thickening (SWT, mm) (r = 0.41 to -0.52; p < 0.04) at any time of assessment. Multiple linear regression analysis revealed baseline EF and lgNT-pro BNP to predict global functional recovery. Patients with NT-pro BNP concentrations 1115 pg/ml did not show significant functional recovery (all p = NS). CONCLUSION NT-pro BNP on day 3 after admission correlates with acute and chronic infarct size and myocardial function after AMI. Global and regional myocardial function did not recover in patients with higher NT-pro BNP (>1115 pg/ml) during subacute phase of AMI.

Prognostic value at 5 years of microvascular obstruction after acute myocardial infarction assessed by cardiovascular magnetic resonance

BackgroundEarly and late microvascular obstruction (MVO) assessed by cardiovascular magnetic resonance (CMR) are prognostic markers for short-term clinical endpoints after acute ST-elevation myocardial infarction (STEMI). However, there is a lack of studies with long-term follow-up periods (>24 months).MethodsSTEMI patients reperfused by primary angioplasty (n = 129) underwent MRI at a median of 2 days after the index event. Early MVO was determined on dynamic Gd first-pass images directly after the administration of 0.1 mmol/kg bodyweight Gd-based contrast agent. Furthermore, ejection fraction (EF, %), left ventricular myocardial mass (LVMM) and total infarct size (% of LVMM) were determined with CMR. Clinical follow-up was conducted after a median of 52 months. The primary endpoint was defined as a composite of death, myocardial re-infarction, stroke, repeat revascularization, recurrence of ischemic symptoms, atrial fibrillation, congestive heart failure and hospitalization.ResultsFollow-up was completed by 107 patients. 63 pre-defined events occurred during follow-up. Initially, 74 patients showed early MVO. Patients with early MVO had larger infarcts (mean: 24.9 g vs. 15.5 g, p = 0.002) and a lower EF (mean: 39% vs. 46%, p = 0.006). The primary endpoint occurred in 66.2% of patients with MVO and in 42.4% of patients without MVO (p < 0.05). The presence of early MVO was associated with a reduced event-free survival (log-rank p < 0.05). Early MVO was identified as the strongest independent predictor for the occurrence of the primary endpoint in the multivariable Cox regression analysis adjusting for age, ejection fraction and infarct size (hazard ratio: 2.79, 95%-CI 1.25-6.25, p = 0.012).ConclusionEarly MVO, as assessed by first-pass CMR, is an independent long-term prognosticator for morbidity after AMI.

Association of copeptin with myocardial infarct size and myocardial function after ST segment elevation myocardial infarction

Objective To investigate the relationship between circulating plasma copeptin values and infarct size as well as myocardial function at baseline and 4 months after mechanical reperfusion for ST segment elevation myocardial infarction (STEMI). Design Prospective observational cohort study. Setting University Hospital of Innsbruck. Patients 54 patients with acute STEMI. Main outcome measures Correlation of plasma copeptin with infarct size as well as left ventricular ejection fraction (LVEF) and remodelling. Methods Participants underwent contrast enhanced cardiac MRI at baseline and 4 months thereafter. Blood samples were drawn 2 days after the onset of symptoms. Copeptin values were determined by an immunofluorescent assay. Results Copeptin concentrations (median 10.4 pmol/l, IQR 6.0–14.4) were associated with early and chronic infarct size (r=0.388, p=0.004 at baseline; r=0.385, p=0.011 at follow-up) and inversely related to LVEF at both times (r=−0.484, p<0.001 at baseline; r=−0.461, p<0.001 at follow-up). Patients with adverse remodelling showed higher baseline copeptin values compared to patients without remodelling (p=0.02). Receiver operating characteristic analysis indicated a cut-off value of 16.7 pmol/l for copeptin to best identify patients with future adverse remodelling. Conclusions Increased copeptin values 2 days after STEMI are associated with larger acute and chronic infarct sizes. Moreover, elevated copeptin concentrations at baseline were associated with myocardial function and remodelling 4 months post-STEMI. These findings strengthen the role of copeptin as a biomarker of adverse outcome after STEMI.

Late microvascular obstruction after acute myocardial infarction: Relation with cardiac and inflammatory markers

OBJECTIVES We sought to assess the relation of late microvascular obstruction (l-MVO) size as quantified by cardiac magnetic resonance (CMR) imaging with cardiac and inflammatory marker concentrations after acute myocardial infarction (AMI). METHODS CMR was performed in 118 consecutive patients within 8 days after successful interventional reperfused first acute ST-elevation AMI. Infarct volumes and l-MVO sizes were calculated from late enhancement (LE) sequences and functional parameters were determined from short-axis cine MR sequences. Creatine kinase (CK) and cardiac troponin T (cTnT), high-sensitivity C-reactive protein (hs-CRP) as well as lactate dehydrogenase (LD) concentrations were determined serially from day 1 to day 4 after symptom onset. RESULTS L-MVO was detected in 66/118 patients (55.9%) and comprised 18.2 ± 10% of infarct size and 4.7 ± 3% of left ventricle myocardial mass. Each single-point, peak and cumulative release concentration of cTnT (r=0.44 to 0.73, p<0.0001), CK (r=0.21 to 0.76, p<0.0001), LD (r=0.36 to 0.82, all p<0.0001) as well as hs-CRP single-point values as assessed from day 1 to day 4 and its peak and cumulative release concentrations (r=0.24 to 0.49, p<0.003) significantly correlated with l-MVO size. Receiver operating curve (ROC) analysis indicated a cut-off value of 4.7 μg/l cTnT to best identify the presence of l-MVO (area under the curve (AUC) 0.904; 95% CI: 0.85-0.95; p<0.0001). CONCLUSION L-MVO sizes significantly correlate with cardiac and inflammatory marker concentrations as determined early after AMI. cTnT concentration of >4.7 μg/l could help to identify patients in whom l-MVO is present.

Assessing myocardial recovery following ST-segment elevation myocardial infarction: short- and long-term perspectives using cardiovascular magnetic resonance

Myocardial recovery after revascularization for ST-segment elevation myocardial infarction (STEMI) remains a significant diagnostic and, despite novel treatment strategies, a therapeutic challenge. Cardiovascular magnetic resonance (CMR) has emerged as a valuable clinical and research tool after acute STEMI. It represents the gold standard for functional and morphological evaluation of the left ventricle. Gadolinium-based perfusion and late-enhancement viability imaging has expanded our knowledge about the underlying pathologies of inadequate myocardial recovery. T2-weighted imaging of myocardial salvage after early reperfusion of the infarct-related artery underlines the effectiveness of current invasive treatment for STEMI. In the last decade, the number of publications on CMR after acute STEMI continued to rise, with no plateau in sight. Currently, CMR research is gathering robust prognostic data on standardized CMR protocols with the aim to substantially improve patient care and prognosis. Beyond established CMR protocols, more specific methods such as magnetic resonance relaxometry, myocardial tagging, 4D phase-contrast imaging and novel superparamagnetic contrast agents are emerging. This review will discuss the currently available data on the use of CMR after acute STEMI and take a brief look at developing new methods currently under investigation.

Intracellular and extracellular T1 and T2 relaxivities of magneto‐optical nanoparticles at experimental high fields

This study reports the T1 and T2 relaxation rates of rhodamine‐labeled anionic magnetic nanoparticles determined at 7, 11.7, and 17.6 T both in solution and after cellular internalization. Therefore cells were incubated with rhodamine‐labeled anionic magnetic nanoparticles and were prepared at decreasing concentrations. Additionally, rhodamine‐labeled anionic magnetic nanoparticles in solution were used for extracellular measurements. T1 and T2 were determined at 7, 11.7, and 17.6 T. T1 times were determined with an inversion‐recovery snapshot‐flash sequence. T2 times were obtained from a multispin‐echo sequence. Inductively coupled plasma‐mass spectrometry was used to determine the iron content in all samples, and r1 and r2 were subsequently calculated. The results were then compared with cells labeled with AMI‐25 and VSOP C‐200. In solution, the r1 and r2 of rhodamine‐labeled anionic magnetic nanoparticles were 4.78/379 (7 T), 3.28/389 (11.7 T), and 2.00/354 (17.6 T). In cells, the r1 and r2 were 0.21/56 (7 T), 0.19/37 (11.7 T), and 0.1/23 (17.6 T). This corresponded to an 11‐ to 23‐fold decrease in r1 and an 8‐ to 15‐fold decrease in r2. A decrease in r1 was observed for AMI‐25 and VSOP C‐200. AMI‐25 and VSOP exhibited a 2‐ to 8‐fold decrease in r2. In conclusion, cellular internalization of iron oxide nanoparticles strongly decreased their T1 and T2 potency. Magn Reson Med, 2010.

In vivo measurement of local aortic pulse-wave velocity in mice with MR microscopy at 17.6 tesla

Transgenic mouse models of human diseases have gained increasing importance in the pathophysiology of cardiovascular diseases (CVD). As an indirect measure of vascular stiffness, aortic pulse‐wave velocity (PWV) is an important predictor of cardiovascular risk. This study presents an MRI approach that uses a flow area method to estimate local aortic pulse‐wave velocity at different sites in the murine aorta. By simultaneously measuring the cross‐sectional area and the through‐plane velocity with a phase‐contrast CINE method, it was possible to measure average values for the PWV in the ascending and descending aorta within the range of 2.4–4.3 m/s for C57BL/6J mice (ages 2 and 8 months) and apoE‐knockout mice (age 8 months). Statistically significant differences of the mean values of the PWV of both groups could be determined. By repeating CINE measurements with a time delay of 1 ms between two subsequent data sets, an effective temporal resolution of 1000 frames/s (fps) could be achieved. Magn Reson Med, 2009.

Cardiac troponin T and creatine kinase predict mid‐term infarct size and left ventricular function after acute myocardial infarction: A cardiac MR study

To assess the relation of cardiac troponin T (cTnT) and creatine kinase (CK) release with infarct size and left ventricular function evaluated during the subacute phase as well as four months after acute myocardial infarction (AMI) by contrast‐enhanced MRI (CE‐MRI).

Multi-vendor, multicentre comparison of contrast-enhanced SSFP and T2-STIR CMR for determining myocardium at risk in ST-elevation myocardial infarction

Aims Myocardial salvage, determined by cardiac magnetic resonance imaging (CMR), is used as end point in cardioprotection trials. To calculate myocardial salvage, infarct size is related to myocardium at risk (MaR), which can be assessed by T2-short tau inversion recovery (T2-STIR) and contrast-enhanced steady-state free precession magnetic resonance imaging (CE-SSFP). We aimed to determine how T2-STIR and CE-SSFP perform in determining MaR when applied in multicentre, multi-vendor settings. Methods and results A total of 215 patients from 17 centres were included after percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction. CMR was performed within 1–8 days. These patients participated in the MITOCARE or CHILL-MI cardioprotection trials. Additionally, 8 patients from a previous study, imaged 1 day post-CMR, were included. Late gadolinium enhancement, T2-STIR, and CE-SSFP images were acquired on 1.5T MR scanners (Philips, Siemens, or GE). In 65% of the patients, T2-STIR was of diagnostic quality compared with 97% for CE-SSFP. In diagnostic quality images, there was no difference in MaR by T2-STIR and CE-SSFP (bias: 0.02 ± 6%, P = 0.96, r2 = 0.71, P < 0.001), or between treatment and control arms. No change in size or quality of MaR nor ability to identify culprit artery was seen over the first week after the acute event (P = 0.44). Conclusion In diagnostic quality images, T2-STIR and CE-SSFP provide similar estimates of MaR, were constant over the first week, and were not affected by treatment. CE-SSFP had a higher degree of diagnostic quality images compared with T2 imaging for sequences from two out of three vendors. Therefore, CE-SSFP is currently more suitable for implementation in multicentre, multi-vendor clinical trials.