Hans-Josef Feistritzer

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.

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.

Galectin-3: Relation to infarct scar and left ventricular function after myocardial infarction

Elevated serum levels of galectin-3, a member of the lectin family, have recently been reported in heart failure patients, aswell as in animal models of heart failure [1–3]. Apart from cardiac remodelling, upregulation of galectin-3 expression and release has also been associated with several other human fibrotic conditions including liver cirrhosis, idiopathic lung fibrosis, pancreatitis and renal failure. Therefore, this lectin is thought to play some regulatory role between inflammation and fibrosis [1]. Its direct mediation of profibrotic pathways such as cell adhesion and proliferation suggests that galectin-3 is involved in the development of heart failure [4,5]. After acute myocardial infarction (AMI), fibrosis and tissue remodelling are the leading causes for the development of heart failure. Cardiacmagnetic resonance (CMR) imagingwith its concept of late enhancement provides high-resolution delineation of myocardial infarction size with diagnostic accuracy and good reproducibility [6,7]. The aim of the present studywas to investigate the correlation of galectin-3 concentrations to CMR-determined myocardial infarction size as well as myocardial function measured four months after STelevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (p-PCI). Blood samples of successfully reperfused STEMI patients (n=29, mean age: 58.1±10.1 yrs) were obtained four months after the acute event. Patients selected for this analysis had no history for any chronic disease. Galectin-3 was measured using an enzyme-linked immunoInternational Journal of Cardiology 163 (2013) 335–344

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.

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.

Fibroblast growth factor 23 as novel biomarker for early risk stratification after ST-elevation myocardial infarction

Objective Adverse left ventricular (LV) remodelling is the major determinant of heart failure and mortality in survivors of ST-elevation myocardial infarction (STEMI). The role of fibroblast growth factor 23 (FGF-23) for LV remodelling prediction after STEMI is unknown. We therefore aimed to investigate the relation between circulating FGF-23 and LV remodelling following revascularised STEMI. Methods In this prospective observational study, we included 88 consecutive patients with STEMI treated by primary percutaneous coronary intervention. FGF-23 concentrations were measured 2 (IQR: 2–2) days after symptom onset. Cardiac magnetic resonance was performed 2 (IQR: 1–3) days as well as 4 (IQR: 4–5) months after infarction to evaluate LV remodelling, defined as ≥20% increase in LV end-diastolic volume. Results Levels of FGF-23 were significantly higher in patients who developed LV remodelling (n=11, 13%) as compared with those without LV remodelling (152.6 (102.5–241.3) vs 75.8 (58.6–105.4) relative units per millilitre, p=0.002). The association between FGF-23 and LV remodelling remained significant (OR: 14.1, 95% CI 2.8 to 70.9; p=0.001) after adjustment for biomarkers reflecting myocardial necrosis (high-sensitivity cardiac troponin T (hs-cTnT)), myocardial stress (N-terminal pro B-type natriuretic peptide (NT-proBNP)) and inflammatory state (high-sensitivity C reactive protein (hs-CRP)). Moreover, a multimarker approach adding FGF-23 to the established LV remodelling-predictive biomarkers (hs-cTnT, NT-proBNP and hs-CRP) led to a net reclassification improvement of 0.92 (95% CI 0.44 to 1.41, p<0.001) and to an integrated discrimination improvement of 0.16 (95% CI 0.08 to 0.24, p<0.001). Conclusions Circulating FGF-23 is independently associated with LV remodelling after reperfused STEMI. A comprehensive multimarker strategy that includes FGF-23 provides incremental prognostic value for prediction of LV remodelling.

Use and limitations of cardiac magnetic resonance derived measures of aortic stiffness in patients after acute myocardial infarction.

INTRODUCTION Cardiac magnetic resonance (CMR) is a unique method to determine regional and local aortic stiffness parameters. Although various methods have been validated, there are no data in patients after acute ST-segment elevation myocardial infarction (STEMI). In the present study we assessed the feasibility of different CMR derived measures of aortic stiffness in patients after first acute STEMI for the first time. METHODS CMR derived aortic pulse wave velocity (PWV) determined by the regional transit-time (PWVTT) and local flow-area (PWVQA) method as well as local distensibility coefficients (DCs) was analyzed in 22 healthy young volunteers and 28 patients with recent acute STEMI. RESULTS PWVTT and DC of the ascending aorta differed significantly between healthy subjects and STEMI patients (all p<0.001). PWVQA at thoracic levels of aorta was not different between groups (p>0.520) and did not correlate with age (p>0.149) and PWVTT (p>0.310). Intra- and interobserver variability was high for PWVTT (r=0.970, p<0.001 and r=0.920, p<0.001), acceptable for DC (all r>0. 809, p<0.001 and all r>0.510, p<0.001) but low for thoracic PWVQA (all r<0.330 and all r<0.372). CONCLUSION PWVTT and local DC are robust methods for the assessment of aortic stiffness in patients after acute STEMI.