Sebastian Johannes Reinstadler

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.

Atorvastatin attenuates murine anti-glomerular basement membrane glomerulonephritis

Statins mediate many of their protective effects by lowering lipids as well as by modulating inflammation. Here, we studied their potential immunomodulatory role in renal inflammation using an autoimmune mouse model of anti-glomerular basement membrane glomerulonephritis. Oral treatment with Atorvastatin dramatically reduced albuminuria and histological changes in the kidneys as compared to vehicle-treated control animals. There was a significant decrease in the Th1 and Th17 response in the regional lymph nodes draining the kidneys. This systemic effect was accompanied by decreased infiltration of the kidneys with inflammatory CD4(+) T and Th17 cells, macrophages, and neutrophils in statin-treated mice. Regulatory T cells were not altered in their number, FoxP3 expression, or suppressive capacity, but their interleukin-10 production was significantly increased by statin treatment. Hence, Atorvastatin systemically and locally decreased the Th1 and Th17 response, thereby protecting the mice against anti-glomerular basement membrane glomerulonephritis. Whether statins can be used to treat human autoimmune renal diseases will require more direct studies.

Comparison of an Oscillometric Method with Cardiac Magnetic Resonance for the Analysis of Aortic Pulse Wave Velocity

Objectives Pulse wave velocity (PWV) is the proposed gold-standard for the assessment of aortic elastic properties. The aim of this study was to compare aortic PWV determined by a recently developed oscillometric device with cardiac magnetic resonance imaging (CMR). Methods PWV was assessed in 40 volunteers with two different methods. The oscillometric method (PWVOSC) is based on a transfer function from the brachial pressure waves determined by oscillometric blood pressure measurements with a common cuff (Mobil-O-Graph, I.E.M. Stolberg, Germany). CMR was used to determine aortic PWVCMR with the use of the transit time method based on phase-contrast imaging at the level of the ascending and abdominal aorta on a clinical 1.5 Tesla scanner (Siemens, Erlangen, Germany). Results The median age of the study population was 34 years (IQR: 24–55 years, 11 females). A very strong correlation was found between PWVOSC and PWVCMR (r = 0.859, p < 0.001). Mean PWVOSC was 6.7 ± 1.8 m/s and mean PWVCMR was 6.1 ± 1.8 m/s (p < 0.001). Analysis of agreement between the two measurements using Bland-Altman method showed a bias of 0.57 m/s (upper and lower limit of agreement: 2.49 m/s and -1.34 m/s). The corresponding coefficient of variation between both measurements was 15%. Conclusion Aortic pulse wave velocity assessed by transformation of the brachial pressure waveform showed an acceptable agreement with the CMR-derived transit time method.

Relation of plasma adiponectin levels and aortic stiffness after acute ST-segment elevation myocardial infarction.

Background: Pulse wave velocity is a measure of aortic stiffness and an independent predictor of cardiovascular morbidity and mortality. Adiponectin is involved in atherosclerosis and inflammation. In the present study we aimed to explore the association between plasma adiponectin concentrations and pulse wave velocity in the acute phase after ST-segment elevation myocardial infarction (STEMI). Methods: Forty-six consecutive STEMI patients (mean age 57±11 years) treated with primary percutaneous coronary intervention (PCI) were enrolled in this cross-sectional study. Plasma adiponectin was measured 2 days after index event by enzyme-linked immunosorbent assay. Aortic pulse wave velocity (PWV) was calculated by the transit-time method with the use of a velocity-encoded, phase-contrast cardiac magnetic resonance protocol. Results: Median plasma adiponectin concentration was 2385 ng/ml (interquartile range 1735–5403). Males had lower plasma adiponectin values than females and current smokers had lower values than non-smokers (all p<0.02). Adiponectin was significantly associated with PWV (r=0.505, p<0.001), age (r=0.437, p=0.002), and total cholesterol (r=0.468, p=0.001). Multiple linear regression analysis revealed adiponectin as a predictor of PWV independently of age, sex, smoking status, total cholesterol, and N-terminal pro-B-type natriuretic peptide (p=0.027). Conclusions: Plasma adiponectin concentrations are strongly associated with aortic stiffness in patients after acute STEMI treated with primary PCI. Our data support a possible role for adiponectin as an independent risk marker for increased aortic stiffness in STEMI patients.

High-sensitivity troponin T for prediction of left ventricular function and infarct size one year following ST-elevation myocardial infarction

BACKGROUND Data relating high-sensitivity cardiac troponin T (hs-cTnT) to long-term myocardial function and infarct size in patients after ST-elevation myocardial infarction (STEMI) are lacking. We aimed to evaluate the use of early hs-cTnT concentrations for prediction of myocardial function and infarct size assessed by cardiac magnetic resonance imaging (CMR) one year following STEMI. METHODS Sixty-six patients, revascularized by primary percutaneous coronary intervention (PCI) for first-time STEMI, were enrolled in this observational study. Serial hs-cTnT, creatine kinase (CK), high-sensitivity C-reactive protein (hs-CRP) and lactate dehydrogenase (LDH) levels were measured on admission, 6 h, 12 h, and 24 h post-PCI. Patients underwent CMR within the first week and 12months thereafter. RESULTS Except for admission hs-cTnT, all single time point and peak hs-cTnT concentrations showed significant correlations with left ventricular ejection fraction (LVEF: r=-0.404 to -0.517, all ps<0.01) and infarct size (IS: r=0.421 to 0.700, all ps<0.01) at baseline and follow-up. The area under the curve (AUC) of peak hs-cTnT was 0.82 (95% CI 0.71-0.92) for the prediction of decreased LVEF (<55%) and 0.89 (95% CI 0.81-0.97) for the prediction of large IS (>8%) at 12months. The combination of all four biomarkers resulted in an AUC of 0.82 and 0.92 for the prediction of reduced LVEF and large IS at 12months, respectively (both ps>0.05). CONCLUSION In stable STEMI patients successfully revascularized by primary PCI, serial and peak concentrations of hs-cTnT are closely correlated to long-term LVEF and IS. Combination of hs-cTnT with CK, hs-CRP, or LDH did not add any significant prognostic value as compared with hs-cTnT alone.

Relation of inflammatory markers with myocardial and microvascular injury in patients with reperfused ST-elevation myocardial infarction

Background: In patients with acute ST-elevation myocardial infarction (STEMI), elevated concentrations of inflammatory markers are correlated with worse clinical outcome. The aim of this study was comprehensively to investigate the relationship of circulating markers of inflammation with myocardial and microvascular damage after STEMI. Methods: In 111 consecutive STEMI patients, blood samples were obtained on admission and from day 1 to day 4 after primary percutaneous coronary intervention and analysed for high-sensitivity C-reactive protein (hs-CRP), white blood cell count and fibrinogen. Cardiac magnetic resonance imaging was performed within the first week and 4 months after primary percutaneous coronary intervention. Results: Peak concentrations of hs-CRP (20.5 (9.6–44.4) mg/L), white blood cell count (12.4 (10.5–15.3) G/L) and fibrinogen (3640 (3150–4550) mg/L) showed significant correlations with both infarct size (r=0.31 to 0.41; P<0.01) and left ventricular ejection fraction (r=−0.29 to −0.39; P<0.01) assessed in the acute as well as chronic stage following STEMI. Furthermore, peak concentrations of these inflammatory markers were significantly higher in patients with microvascular obstruction compared to patients without microvascular obstruction (P⩽0.01). C-statistics revealed that the prognostic values of all three biomarkers for the prediction of large chronic infarct size (>8% of left ventricular myocardial mass) were moderate without significant differences (area under the curve: hs-CRP 0.73 (95% confidence interval (CI) 0.63–0.82), white blood cell count 0.67 (95% CI 0.56–0.78) and fibrinogen 0.69 (95% CI 0.59–0.79); all P>0.12). Combination of inflammatory markers did not significantly increase the area under the curve (P>0.05). Conclusion: In reperfused STEMI patients, increased levels of hs-CRP, white blood cell count and fibrinogen are associated with decreased left ventricular function and more pronounced myocardial damage at baseline and 4 months after infarction.

ST-segment depression resolution predicts infarct size and reperfusion injury in ST-elevation myocardial infarction

Objective ST-elevation myocardial infarction (STEMI) is frequently associated with reciprocal ST-segment depression in contralateral ECG leads. However, the relationship of the resolution of ST-segment depression (STD-R) with myocardial damage is unknown and the potential prognostic value incompletely understood. We sought to evaluate the association between STD-R and markers of myocardial injury as well as to determine the prognostic impact of STD-R in patients with acute reperfused STEMI. Methods We enrolled 611 patients with STEMI in this multicentre cardiac magnetic resonance (CMR) study. STD-R, defined as either worsened (<0%), incomplete (0–50%) or complete (≥50%), was determined 90 min after primary percutaneous coronary intervention (PCI). Patients underwent CMR in median 3 (2–4) days after infarction. Major adverse cardiac events (MACE) were defined as a composite of death, reinfarction and new congestive heart failure within 12 months after enrolment. Results Patients with worsened or incomplete STD-R (n=148 (24.2%)) had a significantly larger area at risk (42 (31–50) vs 37 (29–52) vs 34 (24–46) %LV, p=0.001), larger infarct size (20 (13–30) vs 17(10–26) vs 16 (8–24) %LV, p=0.003), larger extent of microvascular obstruction (0.6(0–3.4) vs 0.4 (0–2.4) vs 0.0 (0–1.4) %LV, p=0.003), and a lower LVEF (46 (39–54) vs 48 (40–56) vs 52 (45–58) %, p<0.001). MACE rate (n=37 (6%)) was significantly higher in patients with worsened (n=10 (19%)) or incomplete STD-R (n=7 (7%)) than in patients with complete STD-R (n=20 (4%), p<0.001). In multivariate Cox regression analysis, categorised STD-R emerged as an independent predictor of MACE at 12 months after adjusting for clinical variables (p=0.007). Conclusions Patients with acute STEMI and worsened or incomplete STD-R after PCI show a more pronounced myocardial as well as microvascular damage as detected by CMR with subsequent independent prognostic information on MACE over a 12-month follow-up period.

Risk stratification by cardiac magnetic resonance imaging after ST-elevation myocardial infarction.

Purpose of review This review summarizes the currently available evidence for the use of cardiac magnetic resonance (CMR) imaging for risk stratifying patients after ST-elevation myocardial infarction (STEMI). Recent findings Growing evidence indicates that CMR imaging allows a comprehensive prognosis assessment in patients following STEMI. Multiple trials have shown that markers of cardiac dysfunction, especially left ventricular ejection fraction, are strongly predictive for clinical events beyond traditional risk factors. Recent data indicate that CMR can be an even more specific marker for the prediction of clinical prognosis by determining the extent of irreversible myocardial and microvascular damage for an individual patient. A multiparametric approach by CMR for optimized risk stratification allows exact infarct sizing and tissue characterization of the jeopardized and infarcted myocardium including microvascular injury. Many of these CMR parameters (infarct size, myocardial salvage, microvascular obstruction, intramyocardial hemorrhage) have demonstrated an incremental prognostic value in addition to clinical risk factors and left ventricular ejection fraction. Summary The comprehensive evaluation of STEMI patients by CMR imaging has the potential to provide incremental prognostic information for risk stratification beyond established clinical risk markers. In light of the lack of trials, however, designed to prospectively test the value of a CMR-guided therapeutic strategy in patients with STEMI, the use of CMR for risk stratification of the postinfarction patient awaits further validation and research.

Association of aortic stiffness with biomarkers of myocardial wall stress after myocardial infarction.

BACKGROUND Aortic pulse wave velocity (PWV) was linked to LV-geometry and -function in patients with kidney disease and non-ischemic cardiomyopathy. The role of aortic compliance after acute STEMI is so far unknown. In the present study, we prospectively investigated the relationship of increased aortic stiffness with biomarkers of myocardial wall stress 4 months after STEMI. METHODS 48 STEMI patients who were reperfused by primary coronary angioplasty underwent cardiovascular magnetic resonance (CMR) at baseline and at 4-month follow-up. The CMR protocol comprised cine-CMR as well as gadolinium contrast-enhanced CMR. Aortic PWV was determined by velocity-encoded, phase-contrast CMR. Blood samples were routinely drawn at baseline and follow-up to determine N-terminal pro-B-type natriuretic peptide (NT-proBNP). In a subgroup of patients, mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-A-type natriuretic peptide (MR-proANP) levels were determined. RESULTS Patients with a PWV above median (>7.0m/s) had significantly higher NT-proBNP, MR-proADM and MR-proANP concentrations at 4-month follow-up than patients with a PWV below median (all p<0.02). PWV showed moderate to good correlation with NT-proBNP, MR-proAMD and MR-proANP levels 4 months after STEMI (all p<0.05). Multivariate analysis revealed PWV, beside myocardial infarct size, as an independent predictor of 4-month NT-proBNP levels after correction for age, creatinine and LV ejection fraction (model r: 0.781, p<0.001). CONCLUSION Aortic stiffness is directly associated with biomarkers of myocardial wall stress 4 months after reperfused STEMI, suggesting a role for aortic stiffness in chronic LV-remodelling.

Prognostic value of left ventricular global function index in patients after ST-segment elevation myocardial infarction

AIMS The left ventricular global function index (LVGFI) is a novel indicator of left ventricular performance. Its prognostic value in patients after ST-segment elevation myocardial infarction (STEMI) is unknown. We sought to evaluate the prognostic significance of LVGFI measured by cardiovascular magnetic resonance (CMR) imaging after STEMI. METHODS AND RESULTS Two hundred eligible STEMI patients (56 ± 11 years, 16% female) revascularized by primary percutaneous coronary intervention were followed-up for 3.1 [2-4.1] years for major adverse cardiac events (MACE). MACE was defined as a composite of death, non-fatal myocardial re-infarction, and new congestive heart failure. All patients underwent CMR imaging within 2 [2-4] days after STEMI. Late enhancement and cine images were acquired to assess myocardial injury as well as myocardial function, including LVGFI. Patients suffering a MACE event (n = 20, 10%) had a significantly lower LVGFI (P = 0.001). In Kaplan-Meier analysis, a decreased LVGFI was associated with a reduced MACE-free survival (P < 0.001). Multivariate Cox regression analysis revealed a decreased LVGFI as a predictor for MACE [hazard ratio = 4.79, 95% confidence interval (CI) 1.46-15.67, P = 0.010] after adjusting for microvascular obstruction, left ventricular mass, and multivessel disease. In receiver operating characteristic analysis, LVGFI was a strong predictor for MACE (area under the curve = 0.73, CI 0.61-0.85). However, c-statistics revealed that LVGFI does not provide incremental prognostic information over left ventricular ejection fraction (LVEF) (P = 0.38). CONCLUSION LVGFI assessed by CMR is a strong predictor of MACE within 3 years after first STEMI. A superior predictive value as compared with LVEF was not found in this study.