Stein Ørn

ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaborati

Authors/Task Force Members: John J.V. McMurray (Chairperson) (UK)*, Stamatis Adamopoulos (Greece), Stefan D. Anker (Germany), Angelo Auricchio (Switzerland), Michael Bohm (Germany), Kenneth Dickstein (Norway), Volkmar Falk (Switzerland), Gerasimos Filippatos (Greece), Cândida Fonseca (Portugal), Miguel Angel Gomez-Sanchez (Spain), Tiny Jaarsma (Sweden), Lars Kober (Denmark), Gregory Y.H. Lip (UK), Aldo Pietro Maggioni (Italy), Alexander Parkhomenko (Ukraine), Burkert M. Pieske (Austria), Bogdan A. Popescu (Romania), Per K. Ronnevik (Norway), Frans H. Rutten (The Netherlands), Juerg Schwitter (Switzerland), Petar Seferovic (Serbia), Janina Stepinska (Poland), Pedro T. Trindade (Switzerland), Adriaan A. Voors (The Netherlands), Faiez Zannad (France), Andreas Zeiher (Germany).

Microvascular obstruction is a major determinant of infarct healing and subsequent left ventricular remodelling following primary percutaneous coronary intervention

AIMS We studied the time-dependent relationships between microvascular obstruction (MO), infarct size, and left ventricular (LV) remodelling after acute myocardial infarction (MI). METHODS AND RESULTS Forty-two consecutive patients with first-time ST-elevation MI, single-vessel disease, successfully treated with primary percutaneous coronary intervention (PCI) were included. Microvascular obstruction, infarct size, and LV remodelling were assessed by cardiac magnetic resonance. Cardiac magnetic resonance was performed at: 2 days, 1 week, 2 months, and 1 year following PCI. Microvascular obstruction was assessed by first-pass perfusion. Patients were divided into three groups according to the presence or absence of MO at 2 days and 1 week: no detectable MO at any time point (11 patients), MO detectable only at 2 days (16 patients), and MO detectable both at 2 days and 1 week (15 patients). In multivariable analysis adjusting for infarct size at 2 days, detectable MO at 1 week was an independent predictor (P = 0.003) of infarct size at 1 year follow-up, associated with adverse infarct healing, adverse LV remodelling, increased LV volumes, and lower ejection fractions when compared with the rest of the cohort. CONCLUSION Microvascular obstruction is an important determinant of infarct healing. The effect of MO on infarct size translated into distinct patterns of LV remodelling during long-term follow-up.

Diagnostic Capability and Reproducibility of Strain by Doppler and by Speckle Tracking in Patients With Acute Myocardial Infarction

OBJECTIVES The objective of the present study was to investigate the ability of strain by Doppler and by speckle tracking echocardiography in the acute phase in patients with ST-segment elevation myocardial infarction (STEMI) to diagnose left ventricular (LV) infarct size. Furthermore, we wanted to study at which time during the cardiac cycle strain should be measured. BACKGROUND The assessment of regional myocardial dysfunction may be an important diagnostic tool in the evaluation of acute myocardial injury. METHODS Strain by Doppler and speckle tracking were assessed in the acute phase and after 10 days in 36 patients (61 +/- 11 years) with STEMI treated with thrombolysis. In a 16-segment model of the LV, peak systolic, end systolic, and peak negative strain were validated against the corresponding myocardial segments measured by contrast-enhanced cardiac magnetic resonance. The 16 segments were averaged to assess LV global longitudinal strain. In addition, 6 segments were analyzed from parasternal short-axis recordings at the papillary muscle level to assess circumferential strain. Reproducibility was tested in 20 patients. RESULTS The different segmental strain assessments separated significantly (p < 0.0001) between the different levels of infarct transmurality regardless of method, with better reproducibility for speckle strain. Circumferential strain separated better than longitudinal strain. With a cutoff value of -13.3% for segmental circumferential strain, sensitivity was 80% and specificity was 74% for prediction of transmural infarction. The LV global strain showed a good correlation with LV infarct size, with the best correlation for LV global peak systolic speckle strain (beta = 0.76, p < 0.0001). CONCLUSIONS On a segmental level, circumferential strain separated transmural from subendocardial necrosis better than longitudinal strain in the acute phase in patients with STEMI. Our findings suggest that in the acute phase in patients treated with thrombolysis, LV global peak systolic speckle strain should be the preferred method for predicting final LV infarct size.

C-reactive protein, infarct size, microvascular obstruction, and left-ventricular remodelling following acute myocardial infarction

AIMS This study assessed the relationship between inflammatory mediators and indices of infarct size and left-ventricular (LV) remodelling following successful primary percutaneous coronary intervention (PCI) in patients with first time ST elevation myocardial infarction (MI). METHODS AND RESULTS Forty-two patients admitted with an occluded single vessel were recruited consecutively. Cardiac magnetic resonance was used for serial assessment (2 days, 1 week, 2 months) of infarct size, microvascular obstruction (MO), and LV remodelling. Inflammatory mediators were analysed before and after PCI. Our major findings were: (1) Following PCI, there was a marked increase in plasma levels of C-reactive protein, closely correlated with an increase in interleukin-6 and terminal complement complex, reaching maximum 2 days after PCI; (2) C-reactive protein 2 days after PCI was significantly correlated with infarct size and parameters of LV remodelling 2 months after PCI; (3) Patients with persistent MO had significantly higher C-reactive protein levels 2 days following PCI. CONCLUSION We suggest that the rapid increase in C-reactive protein levels in this model of successful revascularization of a single, totally occluded vessel reflects the degree of inflammation within the infarcted area. Our findings support a role for C-reactive protein-mediated complement activation as both a marker and mediator of myocardial damage following MI. Clinical study no.: NCT 00465868.

Comparison of left ventricular ejection fraction and left ventricular global strain as determinants of infarct size in patients with acute myocardial infarction.

BACKGROUND The aim was to compare left ventricular ejection fraction (LVEF) and left ventricular (LV) global strain by speckle tracking as predictors of final infarct size. METHODS LV global strain and LVEF by echocardiography were assessed in the acute phase and after revascularization in 39 patients with ST-elevation myocardial infarction treated with thrombolysis. RESULTS After revascularization, global strain and LVEF correlated well with infarct size measured by contrast-enhanced cardiac magnetic resonance. A cutoff value of -15.0% for global strain had a sensitivity of 90% and a specificity of 86% to identify myocardial infarcts larger than 20%. Interobserver variability, expressed by intraclass correlation coefficients, for global strain and LVEF was 0.91 and 0.72, respectively. CONCLUSIONS LV global strain is a more precise diagnostic predictor of large infarcts compared with LVEF and is more reproducible. Global strain measured after revascularization demonstrates advantages over LVEF in the evaluation of LV injury in patients with ST-elevation myocardial infarction.

Myocardial Connective Tissue Growth Factor (CCN2/CTGF) Attenuates Left Ventricular Remodeling after Myocardial Infarction

Aims Myocardial CCN2/CTGF is induced in heart failure of various etiologies. However, its role in the pathophysiology of left ventricular (LV) remodeling after myocardial infarction (MI) remains unresolved. The current study explores the role of CTGF in infarct healing and LV remodeling in an animal model and in patients admitted for acute ST-elevation MI. Methods and Results Transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) and non-transgenic littermate controls (NLC) were subjected to permanent ligation of the left anterior descending coronary artery. Despite similar infarct size (area of infarction relative to area at risk) 24 hours after ligation of the coronary artery in Tg-CTGF and NLC mice, Tg-CTGF mice disclosed smaller area of scar tissue, smaller increase of cardiac hypertrophy, and less LV dilatation and deterioration of LV function 4 weeks after MI. Tg-CTGF mice also revealed substantially reduced mortality after MI. Remote/peri-infarct tissue of Tg-CTGF mice contained reduced numbers of leucocytes, macrophages, and cells undergoing apoptosis as compared with NLC mice. In a cohort of patients with acute ST-elevation MI (n = 42) admitted to hospital for percutaneous coronary intervention (PCI) serum-CTGF levels (s-CTGF) were monitored and related to infarct size and LV function assessed by cardiac MRI. Increase in s-CTGF levels after MI was associated with reduced infarct size and improved LV ejection fraction one year after MI, as well as attenuated levels of CRP and GDF-15. Conclusion Increased myocardial CTGF activities after MI are associated with attenuation of LV remodeling and improved LV function mediated by attenuation of inflammatory responses and inhibition of apoptosis.

Increased interleukin-1β levels are associated with left ventricular hypertrophy and remodelling following acute ST segment elevation myocardial infarction treated by primary percutaneous coronary intervention

Abstract.  Ørn S, Ueland T, Manhenke C, Sandanger Ø, Godang K, Yndestad A, Mollnes TE, Dickstein K, Aukrust P (Stavanger University Hospital, Stavanger; Oslo University Hospital Rikshospitalet; University of Bergen, Bergen; University of Oslo; Oslo; Norway). Increased interleukin‐1β levels are associated with left ventricular hypertrophy and remodelling following acute ST segment elevation myocardial infarction treated by primary percutaneous coronary intervention. J Intern Med 2012; 272: 267–276.

The prognostic value of circulating markers of collagen turnover after acute myocardial infarction.

BACKGROUND We assessed the time profiles and prognostic utility of circulating markers of collagen turnover (CTO) following acute myocardial infarction (MI). In contrast to previous studies, no patient had been pre-treated with inhibitors of the renin-angiotensin-aldosterone system (RAAS) at the time of initial assessment. METHODS Plasma levels of N-terminal fragment of type I collagen (PINP), carboxy-terminal telopeptide of type I collagen (ICTP), N-terminal fragment of type III collagen (PIIINP), matrix metalloproteinase-1(MMP-1) and tissue inhibitor of MMPs type-1 (TIMP-1) were assessed in 233 patients following acute MI. The CTO markers were initially assessed prior to treatment by either captopril or losartan, at a median of 3 days following MI. In addition, blood samples were acquired at 1 month, 1 year and 2 years following MI. Development of heart failure symptoms, all-cause and cardiovascular death were recorded as endpoints during two years of follow-up. RESULTS With the exception of PIIINP, all CTO markers demonstrated significant longitudinal changes following MI. At baseline, ICTP (p<0.0001) and TIMP-1 (p=0.01) levels were significantly elevated in patients who later died compared with survivors. In multivariable analysis only ICTP reached statistical significance as predictor of all cause death (p=0.048). In patients developing symptoms of heart failure during follow-up, ICTP was the only significantly elevated CTO marker (p<0.01). CONCLUSION The present study supports a prognostic role for ICTP in both the acute and chronic phase following MI.

Increased Systemic and Local Interleukin 9 Levels in Patients with Carotid and Coronary Atherosclerosis

Objective Atherosclerosis is a chronic inflammatory disorder that involves a range of inflammatory mediators. Although interleukin (IL)-9 has been related to inflammation, there are at present no data on its role in atherosclerosis. Here we have examined IL-9 and IL-9 receptor (IL-9R) systemically and locally in patients with coronary and carotid atherosclerosis. Methods Plasma IL-9 was quantified by enzyme immunoassay and multiplex technology. IL-9 and IL-9R mRNA were quantified by real-time RT-PCR, and their localization within the lesion was assessed by immunohistochemistry. Results The main findings were: (i) Patients with carotid atherosclerosis had significantly raised IL-9 plasma levels compared with healthy controls (n = 28), with no differences between asymptomatic (n = 56) and symptomatic (n = 88) patients. (ii) On admission, patients with acute ST-elevation myocardial infarction (STEMI) (n = 42) had markedly raised IL-9 plasma levels which gradually declined during the first week post-MI. (iii) T cells and monocytes from patients with unstable angina (n = 17) had increased mRNA levels of IL-9 as compared with controls (n = 11). (iv) Carotid plaques (n = 68) showed increased mRNA levels of IL-9 and IL-9R compared to non-atherosclerotic vessels (n = 10). Co-localization to T cells (IL-9 and IL-9R) and macrophages (IL-9) were shown by immunohistochemistry. (v) IL-9 increased IL-17 release in peripheral blood mononuclear cells from patients with unstable angina (n = 5) and healthy controls (n = 5) with a particularly enhancing effect in cells from the patient group. Conclusion Our findings show increased IL-9 levels in different atherosclerotic disorders both systemically and within the lesion, suggesting a role for the IL-9/IL-9R axis in the atherosclerotic process, potentially involving IL-17 mediated mechanisms. However, the functional consequences of these findings should be further investigated.

Duration of Myocardial Early Systolic Lengthening Predicts the Presence of Significant Coronary Artery Disease

OBJECTIVES This study sought to investigate whether the duration of left ventricular (LV) early systolic lengthening could accurately identify patients with significant coronary artery disease (CAD). BACKGROUND Ischemic myocardium with reduced active force will lengthen when LV pressure rises during early systole before onset of systolic shortening. METHODS We included 88 patients with suspected CAD referred to elective diagnostic coronary angiography. Two of these patients were excluded from the study due to evidence of previous myocardial infarction on contrast-enhanced magnetic resonance imaging. Speckle tracking echocardiography was performed before coronary angiography and at follow-up scheduled 1 year after revascularization, and global longitudinal strain and duration of average LV early systolic lengthening were recorded. RESULTS Forty-three of 86 patients had significant CAD. The duration of early systolic lengthening was significantly prolonged in patients with significant CAD compared with patients without significant coronary artery stenoses (76 ± 37 ms vs. 38 ± 23 ms, p < 0.001). Correspondingly, global systolic strain was significantly lower in patients with CAD (-17.7 ± 3.0% vs. -19.5 ± 2.6%, p = 0.003). Prolonged duration of early systolic lengthening showed the best accuracy in detecting CAD, with an area under the receiver-operating characteristic curve of 0.83. The area under the curve for global strain was 0.68. At 1-year follow-up, the duration of early systolic lengthening was significantly reduced (64 ± 37 ms vs. 76 ± 37 ms, p = 0.041) in the patients treated with revascularization. CONCLUSIONS Duration of myocardial early systolic lengthening was prolonged in patients with significant CAD; this might be a useful parameter to identify patients who might benefit from reperfusion therapy.