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Aims: To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF).Methods and Results: TRANSITION was a randomised, multicentre, open-label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre-admission use of renin-angiotensin-aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12-h pre-discharge or between Days 1-14 post-discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up- or down-titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from the day of discharge was Day -1 and Day +1 in the pre-discharge group and the post-discharge group, respectively. Comparable proportions of patients in the pre- and post-discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79-1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83-0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92-1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90-2.46).Conclusions: Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks.Clinical Trial Registration: ClinicalTrials.gov ID: NCT02661217. [ABSTRACT FROM AUTHOR]

Objectives: The extracellular matrix is involved in wound repair after acute myocardial infarction (AMI). We investigated whether matrix metalloproteinase (MMP)-9, tissue inhibitor of metalloproteinases (TIMP)-1, and the MMP inducer (EMMPRIN) are associated with infarct size, left ventricular function, and clinical outcome in ST-elevation-MI (STEMI). Methods: In 243 STEMI patients, circulating EMMPRIN, MMP-9, and TIMP-1 were analyzed 3 days and 3 months post-AMI. Infarct size and left ventricular ejection fraction were assessed by single-photon emission computed tomography (SPECT) ( n = 230/226) and MRI ( n = 111/167) at 3 months. Results: EMMPRIN, MMP-9, and TIMP-1 levels and the MMP-9/TIMP-1 ratio declined from day 3 to 3 months ( p < 0.001, all). TIMP-1 levels at day 3 correlated significantly with SPECTand MRI-based infarct size, troponin T ( p < 0.04, all), and amino-terminal pro-B-type natriuretic peptide (NT-proBNP; p < 0.001). The upper quartile of day 3 TIMP-1 levels showed an adjusted odds ratio of 5.0 (95% confidence interval 1.2-20.6) for having a large infarct size. An insignificant relationship between MMP-9 and clinical events within 1 year (death, AMI, or stroke) ( n = 15) was observed, probably due to the lack of statistical power. Conclusion: The decline in EMMPRIN, MMP-9, and TIMP-1 3 months after acute STEMI is probably due to initial acute-phase processes. The associations between TIMP-1, infarct size, and NT-proBNP indicate a role for TIMP-1 in cardiac remodeling. [ABSTRACT FROM AUTHOR]

Objectives. The aim of this study was to compare health-related quality of life (HRQoL) scores obtained from the instrument Short Form (SF)-36 through the so-called SF-6D utilities, and those obtained from 15D, in patients with ST-elevation myocardial infarction (STEMI), and to evaluate the consequences in estimation of quality adjusted life years (QALYs). Design. This was a sub-study of the Norwegian District Treatment of STEMI, in which patients with STEMI treated with tenecteplase, were randomized to early angioplasty or standard management ( n = 266). HRQoL data were collected at all visits (0, 1, 3, 7 and 12 months). All patients with complete data were included ( n = 248). Results. The score range was 0.33-1.0 for SF-6D and 0.49-1.0 for 15D. Mean utility scores from 15D were higher and had different distribution compared to scores from SF-6D. Mean QALY for the whole group was higher using 15D than SF-6D (0.89 vs. 0.77). The incremental number of QALYs with early angioplasty compared to standard treatment was 0.005 (95% CI: − 0.018 to 0.028) using SF-6D, and 0.004 (95% CI: − 0.010 to 0.018) using the 15D instrument. Conclusions. Choice of instrument may influence HRQoL scores, but not necessarily the gain in QALYs. [ABSTRACT FROM AUTHOR]

Aims Magnetic resonance imaging (MRI) is often considered to be the gold standard in measuring left ventricular function and volumes. The aim of this study was to assess the agreements between standard echocardiography (standard echo), contrast echocardiography (contrast echo), single-photon emission computed tomography (SPECT), and MRI in the determination of left ventricular ejection fraction (EF) and end-diastolic volumes (EDV) in patients treated for acute ST-elevation myocardial infarction (STEMI). Methods and results Standard echo, contrast echo, SPECT and MRI were performed on the same day, 3 months after STEMI in 150 patients participating in the NORwegian Study on District Treatment of ST-Elevation Myocardial Infarction (NORDISTEMI). Bland–Altman analysis of EF measured by all four imaging modalities showed generally low mean differences but wide limits of agreement. The mean EDV difference, however, was consistently higher when MRI was compared with standard echo (54.9 mL), contrast echo (41.7 mL) and SPECT (54.6 mL), and the limits of agreement were wider. The mean EDV differences between contrast echo vs. standard echo, SPECT vs. standard echo and contrast echo vs. SPECT were small. Conclusion Our data suggest that all four imaging modalities measured EF closely similar after STEMI as demonstrated by a very small bias. The limits of agreement were however wide. EDV measured by MRI was consistently higher when compared with the other methods which may be caused by different tracing-methods and imaging principles. As echocardiography is preferable from a cost-benefit point of view, further analysis would be needed to clarify the nature of such differences. [ABSTRACT FROM AUTHOR]

Background. In patients with the metabolic syndrome, the prevalence of cardiovascular disease, disease-related morbidity and mortality are reported to be significantly higher than in a population without the metabolic syndrome. We investigated the role of metabolic syndrome and related biomarkers as predictors of infarct size in patients with their first myocardial infarction. Methods. This was a cross-sectional sub-study from the 3 months follow-up in the NORwegian Study of DIstrict treatment of ST-Elevation Myocardial Infarction (NORDISTEMI), including 152 consecutive patients, all initially treated with thrombolysis. Infarct size after 3 months was determined by late gadolinium enhanced magnetic resonance imaging, measuring ventricular infarct volume in absolute and relative terms. Results. At 3 months, 33 patients (22%) were categorized as having metabolic syndrome. There was no significant difference in median infarct size between those presenting with and without the metabolic syndrome [relative infarct volume 9.0 (4.8, 15.1) % vs. 8.3 (2.9, 13.6)%, p = 0.34]. Adjusting for possible confounders did not alter the results essentially. Circulating levels of IL-18, CRP and PAI-I activity were significantly higher in patients with the metabolic syndrome while adiponectin concentrations were significantly lower ( p ≤ 0.01 for all). None of these variables were associated with myocardial infarct size. Conclusions. No association between the presence of metabolic syndrome and related biomarkers, and the size of the myocardial infarction was apparent in this study population. [ABSTRACT FROM AUTHOR]

Objectives: The evaluation of infarct size and left ventricular function after acute myocardial infarction is important for predicting the subsequent clinical course. This assessment can be achieved by non-invasive imaging methods, but biochemical assays are frequently used as an alternative. We investigated the ability of a single measurement of cardiac troponin T (cTnT) the third morning after onset of ST-segment elevation myocardial infarction (STEMI) to predict infarct size and left ventricular ejection fraction (LVEF). Methods: The study population consisted of 103 patients with their first STEMI treated with thrombolysis. Blood samples for determination of cTnT were drawn the third morning after onset of symptoms. Infarct size and LVEF were assessed by magnetic resonance imaging 3 months later. Results: Linear regression analysis showed a strong, significant correlation between third-day cTnT and infarct size at 3 months (r = 0.84, p < 0.0001). A significant but inverse and weaker correlation was obtained between third-day cTnT and LVEF (r = –0.63, p < 0.0001). Adjusting for age, gender, infarct location and medication changed the results marginally. Conclusions: A single cTnT value the third morning after onset of STEMI predicted the final infarct size in this group of patients with their first STEMI, and might be useful for ruling out impaired LVEF. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives. Thrombolysis is the treatment of choice for patients with ST-elevation myocardial infarction (STEMI) living in rural areas with long transfer delays to percutaneous coronary intervention (PCI). This trial compares two different strategies following thrombolysis: to transfer all patients for immediate coronary angiography and intervention, or to manage the patients more conservatively. Design. The NORwegian study on DIstrict treatment of STEMI (NORDISTEMI) is an open, prospective, randomized controlled trial in patients with STEMI of less than 6 hours of duration and more than 90 minutes expected time delay to PCI. A total of 266 patients will receive full-dose thrombolysis, preferably prehospitally, and then be randomized to either strategy. Our primary endpoint is the one year combined incidence of death, reinfarction, stroke or new myocardial ischaemia. The study is registered with ClinicalTrials.gov, number NCT00161005. Results. By April 2006, 109 patients have been randomized. Thrombolysis has been given prehospitally to 52% of patients. The median transport distance from first medical contact to catheterization laboratory was 155 km (range 90–396 km). Results of the study are expected in 2008. [ABSTRACT FROM AUTHOR]