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Aims None of the existing studies on adherence have directly measured levels of all medications (or their metabolites) in patients with heart failure (HF). Methods and results We used liquid chromatography–tandem mass spectrometry to measure the presence of prescribed drugs (diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists) in the urine of patients reviewed 4–6 weeks after hospitalization with HF. Patients were unaware that adherence was being assessed. Of the 341 patients studied, 281 (82.4%) were adherent, i.e. had all prescribed drugs of interest detectable in their urine. Conversely, 60 patients (17.6%) were partially or completely non-adherent. Notably, 24 of the 60 were non-adherent to only diuretic therapy and only seven out of all 341 patients studied (2.1%) were completely non-adherent to all prescribed HF drugs. There were no major differences in baseline characteristics between adherent and non-adherent patients. Conclusion Non-adherence, assessed using a single spot urine measurement of drug levels, was confirmed in one of five patients evaluated 4–6 weeks after hospitalization with HF.

Aims: In recent years there has been an increase in the number of biomarkers in heart failure ( HF ). The clinical role for these novel biomarkers in combination is not clear. Methods and results: The following novel biomarkers were measured from 628 patients recently hospitalized with decompensated HF; mid-regional pro-adrenomedullin ( MR-proADM ), mid-regional pro-atrial natriuretic peptide ( MR-proANP ), copeptin, high-sensitivity cardiac troponin T ( hs-cTnT ), ST2, galectin-3, cystatin C, combined free light chains ( cFLC ) and high sensitivity C-reactive protein ( hsCRP ). The incremental prognostic value of these novel biomarkers was evaluated within an extensive model containing established predictors of mortality. During a mean ( SD ) follow-up of 3.2 ( 1.5 ) years, 290 ( 46% ) patients died. Elevated concentrations of all novel biomarkers were associated with an increased unadjusted risk of mortality but only two-thirds were independent predictors following multivariable analysis. Using dichotomized cut-points from receiver operating characteristic analysis, MR-proADM, hs-cTnT, cFLC, hsCRP, and ST2 remained independent predictors of mortality. Further dichotomization into low ( 0–2 elevated biomarkers ) or high ( at least three of the five biomarkers elevated ) risk groups provided greatest incremental prognostic value ( hazard ratio 2.20, 95% confidence interval 1.37–3.54; P = 0.001 ) and improved the performance of the model ( C-statistic 0.730 from 0.721, net reclassification index 32.5% ). Conclusion: The novel biomarkers included in this study added little, if any, incremental prognostic value on their own to a model containing established predictors of mortality. However, following dichotomization, five of the novel biomarkers provided incremental prognostic value. There was a clear gradient in the risk of death with increasing numbers of elevated novel biomarkers, with the presence of at least three identifying patients at greatest risk of mortality.

Background:\ud \ud Estimation of strain parameters from cine acquisitions, such as balanced steady state free precession (b-SSFP) is advantageous, as it would obviate the need for acquisition of additional strain sequences reducing scanning time and making strain more accessible to clinicians. 2D strain derived from feature-tracking is now commercially available. The GlasgowHeart cine-strain method is designed to overcome some limitations of currently available feature-tracking methods by estimating pixel-wise strain for myocardial deformation incorporating all of the myocardial tissues. The aims of this pilot study was to ensure that 2D peak circumferential strain estimated from the GlasgowHeart method is feasible in healthy volunteers (n = 20) and reproducible with minimal intra- and inter- observer variability.\ud \ud Methods:\ud \ud Healthy volunteers aged at least 18 years of age with no prior medical history were invited to participate. A subset of 20 healthy adult volunteers underwent 1.5T CMR twice, < 2 days apart. Written consent was obtained. Mid-LV cine sequences, were analysed with the GlasgowHeart software. The process involves contouring the myocardial borders at end-diastole and segmenting the myocardium by using the right ventricular insertion point according to the 16 segment AHA model. Two observers independently analysed 40 short axis slices using the cine-strain method for inter-observer variability. One observer re-analysed the 40 short axis slices 10 days later for intra-observer variability. Scans were analysed in a random order. Pearson correlation and Bland-Altman analysis were used to analyse the data.\ud \ud Results:\ud \ud 20 participants were used in the subset analysis (mean age ± SD 49.5 years (17.2) 50% male). Peak circumferential strain (Ecc) measured on the first set of MRIs by the two observers (Figure 2A,B) was highly correlated (R = 0.915, p < 0.001) and in excellent agreement (mean difference = 0.01; 95% LoA: -0.01, 0.02). The repeated image analysis (Figure 2C,D) also disclosed a high degree of association in paired measurements of Ecc that was strongly correlated(R= 0.915, p< 0.001) and in excellent agreement (mean difference = 0.00; 95% LoA: -0.02, 0.01). Ecc measured in the second set of MRIs by 2 observers was well correlated (R = 0.937, p < 0.001) and in excellent agreement (mean difference = 0.00; 95% limits of agreement were -0.016 and 0.021). The repeated image analysis at follow-up yielded Ecc that was well correlated(R= 0.942, p < 0.001) and in excellent agreement (mean = 0.00; 95% LoA: -0.009 and 0.009). There was no difference between the average global Ecc at different time points (p > 0.05).

The significance of remote myocardium in the natural history of STEMI is uncertain. Cardiac magnetic resonance (CMR) depicts left ventricular (LV) dimension and pathology. Native T1 quantified by CMR (T1 proton relaxation time, milliseconds) is a fundamental tissue property determined by water

Objectives This study investigated the prevalence and potential incremental prognostic value of combined free light chains (cFLCs) in patients recently hospitalized with decompensated heart failure (HF). Background Inflammatory pathways are recognized in the pathogenesis and progression of HF. Free light chain (FLC) elevation is conventionally associated with monoclonal gammopathies, including multiple myeloma. Polyclonal increases in both kappa and lambda FLCs occur in autoimmune and other chronic inflammatory conditions. Recently, a novel assay for measuring kappa and lambda immunoglobulin FLCs together, known as combined free light chain (cFLC) has been developed. Methods Six hundred twenty-eight patients recently hospitalized with decompensated HF were studied. cFLCs were measured by turbidimetry using an immunoassay. The incremental prognostic value of cFLCs for mortality was evaluated using Cox proportional hazard models including 22 established predictors of outcome in HF. Results Of 628 patients, 290 (46%) died during a follow-up of 3.2 ± 1.5 years. Two hundred seventy patients (43%) had elevated cFLCs. There was a clear gradient in the risk of death according to cFLC quartile, with those in the top quartile having an unadjusted risk of mortality more than twice that of those in the lowest quartile (hazard ratio: 2.38; p < 0.0001). After multivariable analysis, cFLC remained an independent predictor of mortality, with an almost 50% higher adjusted risk for those in the top compared with bottom quartile. Older age, lower body mass index, New York Heart Association classification III/IV, previous myocardial infarction, current smoking and B-type natriuretic peptide, bilirubin, high-sensitivity C-reactive protein, glycated hemoglobin, and lymphocyte concentrations were also independent predictors of mortality. Conclusions cFLCs are an independent predictor of mortality in patients recently hospitalized with decompensated HF. Further work is required to assess the effects of HF therapies on cFLC concentrations and whether or not directly targeting this marker of inflammation improves prognosis for patients with HF.

Background: Myocardial longitudinal relaxation time (T1, ms) is a fundamental magnetic property of tissue that is related to water content and mobility. The pathophysiological and prognostic importance of native myocardial T1 values in acute STEMI patients is unknown. We aimed to assess the clinical significance of infarct tissue characteristics using native T1 cardiac magnetic resonance (CMR).\ud \ud Methods: We performed a prospective single center cohort study in reperfused STEMI patients who underwent CMR 2 days and 6 months post-MI. Native T1 CMR (MOLLI investigational prototype sequence: 3 (3) 3 (3) 5) was measured in myocardial regions-of-interest. The area-at-risk and infarct territory were depicted with T1 mapping and late gadolinium contrast enhancement imaging, respectively. All-cause death or heart failure hospitalization was a pre-specified outcome that was assessed during follow-up.\ud \ud Results: 300 STEMI patients (mean±SD age 59±12 years, 74% male, 114 with anterior STEMI) gave informed consent and had CMR (14 July 2011 - 22 November 2012). Of these, 288 STEMI patients had evaluable T1 maps and follow-up assessments (median duration 845 days). Infarct size was 18 ±14% of left ventricular mass. Microvascular obstruction occurred in 160 (55.6%) patients. Native T1 within the area-at-risk (1097 ±52 ms) was higher than in the remote zone (961 ±25 ms; p

Background:\ud Myocardial longitudinal relaxation time (T1, ms) is a fundamental magnetic property of tissue that is related to water content and mobility. The pathophysiological and prognostic importance of native myocardial T1 values in acute ST-elevation myocardial infarction (STEMI) patients is unknown. We aimed to assess the clinical significance of infarct core native T1.\ud Methods:\ud We performed a prospective single center cohort study in reperfused STEMI patients who underwent CMR 2 days and 6 months post-MI. Native T1 CMR (MOLLI investigational prototype sequence: 3 (3) 3 (3) 5) was measured in myocardial regions-of-interest. The infarct territory and microvascular obstruction (MVO) were depicted with late gadolinium enhancement CMR. Adverse remodeling was defined as an increase in LV end-diastolic volume (LVEDV) ≥ 20% at 6 months. All-cause death or heart failure hospitalization was a pre-specified outcome that was assessed during follow-up.\ud \ud Results:\ud 300 STEMI patients (mean±SD age 59±12 years, 74% male, 114 with anterior STEMI) gave informed consent and had CMR (14 July 2011 - 22 November 2012). Of these, 288 STEMI patients had evaluable T1 maps. Infarct size was 18 ±14% of LV mass. One hundred and forty five (50%) of 288 patients had late MVO, whereas 160 (56%) patients had infarct core pathology revealed by native T1. Native T1 within the infarct core (996.9±57.3; p

Background The clinical significance of infarct extracellular volume (ECV) post-STEMI is unknown. ECV can be estimated by cardiac magnetic resonance imaging (CMR) using T1 MOLLI maps. We measured infarct ECV in STEMI survivors, and assessed the relationships between ECV and markers of MI severity. Methods STEMI survivors were enrolled in a single-centre cohort study (BHF MR-MI study – NCT02072850). Culprit artery flow was described by thrombus in myocardial infarction (TIMI) classification. CMR was performed at 1.5 Tesla (Siemens MAGNETOM Avanto) 2-days and 6-months post-MI, including T1-mapping with MOLLI before and 15-minutes after contrast (0.15 mmol/kg gadoterate meglumine). ECV was analysed by outlining regions-of-interest (ROIs) in infarcted myocardium, including microvascular obstruction, and left ventricular (LV) blood pool. ECV was calculated as the relaxation rate (R1=1/T1) for myocardium and LV blood pool before vs. after contrast, corrected for haematocrit. ECV was compared with TIMI-flow pre- and post-percutaneous coronary intervention (PCI) and ST-segment resolution. A reduction in ST-segment voltage of ≥70% was considered complete ST-resolution and Results 201 STEMI patients (age 58 ± 11 years; 156 (77%) male) were enrolled. Infarct ECV was similar at baseline and follow-up (51.3 ± 9.5% vs. 50.3 ± 12.0%, p = 0.1). Pre-PCI, 131 (65%) patients had TIMI-flow 0 and 70 (35%) had TIMI-flow 1–3. Post-PCI, 3 (1.5%) patients had TIMI-flow 0 and 198 (98.5%) had TIMI-flow 2–3. TIMI-flow 0 pre-PCI was associated with higher infarct ECV at baseline (p Conclusion Preserved culprit artery flow and complete ST-resolution are associated with lower infarct ECV at baseline and follow-up. Clinical and electrocardiographic markers of MI severity are predictors of interstitial expansion in the infarct zone in STEMI patients.

Objectives The aim of this study was to assess whether deferred stenting might reduce no-reflow and salvage myocardium in primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Background No-reflow is associated with adverse outcomes in STEMI. Methods This was a prospective, single-center, randomized, controlled, proof-of-concept trial in reperfused STEMI patients with ≥1 risk factors for no-reflow. Randomization was to deferred stenting with an intention-to-stent 4 to 16 h later or conventional treatment with immediate stenting. The primary outcome was the incidence of no-/slow-reflow (Thrombolysis In Myocardial Infarction ≤2). Cardiac magnetic resonance imaging was performed 2 days and 6 months after myocardial infarction. Myocardial salvage was the final infarct size indexed to the initial area at risk. Results Of 411 STEMI patients (March 11, 2012 to November 21, 2012), 101 patients (mean age, 60 years; 69% male) were randomized (52 to the deferred stenting group, 49 to the immediate stenting). The median (interquartile range [IQR]) time to the second procedure in the deferred stenting group was 9 h (IQR: 6 to 12 h). Fewer patients in the deferred stenting group had no-/slow-reflow (14 [29%] vs. 3 [6%]; p = 0.006), no reflow (7 [14%] vs. 1 [2%]; p = 0.052) and intraprocedural thrombotic events (16 [33%] vs. 5 [10%]; p = 0.010). Thrombolysis In Myocardial Infarction coronary flow grades at the end of PCI were higher in the deferred stenting group (p = 0.018). Recurrent STEMI occurred in 2 patients in the deferred stenting group before the second procedure. Myocardial salvage index at 6 months was greater in the deferred stenting group (68 [IQR: 54% to 82%] vs. 56 [IQR: 31% to 72%]; p = 0.031]. Conclusions In high-risk STEMI patients, deferred stenting in primary PCI reduced no-reflow and increased myocardial salvage. (Deferred Stent Trial in STEMI; NCT01717573 )

Background: The pathophysiological basis of reperfusion injury in smokers is incompletely understood. Methods: Patients with acute STEMI were prospectively enrolled during emergency PCI, and categorized according to a current smoking status (yes/no). Contrast-enhanced MRI at 1.5T was acquired 2

Background: The segmental extent of late gadolinium enhancement imaged with cardiac magnetic resonance early after acute ST-segment elevation myocardial infarction (STEMI) has weak spatial correspondence with final infarct on follow-up, thus its prognostic value is uncertain. We hypothesized that

Background Myocardial haemorrhage is a prognostically important complication of acute ST-elevation myocardial infarction (STEMI). Persistence of haemoglobin degradation products within infarct scar tissue and the potential clinical significance have not been investigated. Methods and Results Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI; ClinicalTrials.gov: NCT02072850). 211 patients (mean (SD) age 57 (11) years, 77% male) had evaluable T2* cardiac magnetic resonance (CMR) imaging (1.5 Tesla) 2 days 6 months post-MI. Myocardial haemorrhage was defined as a hypointense infarct core with T2* signal de novo haemorrhage after the first CMR scan. Clinical associates of a persistent hypointense core at 6 months included hypertension (odds ratio (95% confidence interval) 0.28 (0.08, 0.95); p = 0.040), heart rate (1.08 (1.03, 1.13); p = 0.001), systolic blood pressure (1.06 (1.01, 1.12); p = 0.015), neutrophil count (2.19 (1.01, 4.74); p = 0.048), left anterior descending as culprit artery (9.26 (1.26, 67.99); p = 0.029), infarct size (1.10 (1.03, 1.17); p = 0.004) and initial haemorrhage size (1.34 (1.06, 1.66); p = 0.012). A hypointense infarct core with T2*-mapping at 6 months was associated with worsening LV end-diastolic volume (regression coefficient (95% confidence interval) 15.43 (1.35, 29.50); p = 0.032) and worsening left ventricular ejection fraction (-4.15 (-7.40, -0.89); p = 0.013). Conclusion Persistence of haemoglobin degradation products at 6 months post-STEMI is common and prognostically important.

Background The natural history of persistent myocardial oedema after ST-elevation myocardial infarction (STEMI) is uncertain. Methods and ResultsPatients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI; ClinicalTrials.gov: NCT02072850). Cardiac magnetic resonance (CMR) imaging with T2-mapping of myocardial oedema was performed at 1.5 Tesla 2 days and 6 months post-MI. Myocardial oedema was defined as infarct signal intensity (S. I.) >2 standard deviations from the mean S. I. within a remote reference region. 283 STEMI patients (mean (SD) age 59 (12) years, 75% male) were enrolled. Infarct size was 18 (13)% of left ventricular (LV) mass. At 2 days, infarct zone T2 (ms) was higher than remote zone T2 (62.9 (5.2) vs. 49.7 (2.1); p Conclusion Persistence of oedema within the infarct zone affected the majority of patients at 6 months post-STEMI, and was associated with the initial severity of STEMI and adverse LV remodelling.

Background Despite the success of emergency PCI for acute STEMI, failed myocardial reperfusion (microvascular obstruction) is common and prognostically important, but it commonly passes undetected in clinical practice. Purpose To investigate coronary flow reserve (CFR) and the index of microvascular resistance (IMR) in the culprit coronary artery in patients with acute reperfused STEMI. Methods CFR and IMR were measured at the end of PCI using guidewire-based thermodilution (n = 283; mean age 60 (12) years, 73% male). CMR imaging was used to assess left ventricular (LV) function and infarct pathology 2 days and 6 months post-MI (n = 264). All-cause death or first heart failure hospitalisation (ACD) was a pre-specified outcome that was assessed during follow-up (median duration 845 days). Results The median [IQR] CFR was 1.6 [1.1–2.1] and the median IMR was 25 [15–48]. Microcirculatory status was associated with Killip Heart Failure classification, ST-segment resolution, LV ejection fraction and infarct size and pathology revealed by CMR 2 days later. In multivariate analysis, the combination of a CFR 25 was associated with changes in both LV ejection fraction (-2.47 (95% CI: -4.45, -0.49); p = 0.015) and LV end-diastolic volume (8.49 (1.96, 15.92); p = 0.025), and a CFR median was a multivariable (2.96 (1.24, 7.08); p = 0.015) associate of ACD. Conclusions The combination of a reduced CFR and an increased IMR immediately identifies patients who have a substantially increased risk of adverse LV outcomes and all-cause death or heart failure.

Background The GlasgowHeart method is designed to overcome some limitations of currently available feature-tracking methods by incorporating all of the myocardial tissues using an in-house developed intensity-based b-spline deformable registration method. The aim of this pilot study was to ensure that peak circumferential strain (Ecc) estimation is feasible and reproducible with minimal intra- and inter- observer variability. Methods 20 healthy volunteers underwent 1.5T CMR twice, Results 20 participants were used in the analysis (mean age ± SD 49.5 years (17.2) 50% male). Ecc measured on the first set of MRIs by the two observers was highly correlated (R = 0.915, p 0.05). Conclusion The GlasgowHeart method is a robust and reproducible method of assessing cine-derived circumferential strain. By tracking a higher proportion of voxels than the currently available feature tracking software, it has clear potential to provide a more accurate assessment of strain.

Despite the success of emergency percutaneous coronary intervention (PCI) for acute ST-elevation myocardial infarction (STEMI), failed myocardial reperfusion (microvascular obstruction (MVO)) is common and prognostically important. Our aim was to compare coronary flow reserve (CFR), a measure of

Background The natural history and clinical significance of myocardial extracellular volume (ECV) in infarcted myocardium post-STEMI is uncertain. ECV can be estimated by cardiac magnetic resonance imaging (CMR). We measured infarct ECV of STEMI survivors, and assessed the relationships with clinical findings. Methods STEMI survivors were enrolled in a cohort study (BHF MR-MI study – NCT02072850). CMR was performed at 1.5 Tesla (Siemens MAGNETOM Avanto) 2 days and 6 months post-MI. T1 MOLLI mapping was performed pre- and 15 min post-contrast (0.15 mmol/kg gadoterate meglumin). ECV was calculated as the difference in relaxation rate (R1 = 1/T1) for myocardium and LV blood pool pre- vs. post-contrast, corrected for haematocrit (HCT). The percentage change in infarct ECV was calculated (%ΔECV). Results 129 patients (59 ± 11 years; 98 (76%) male) were included. Infarct ECV at baseline and follow-up was similar (49.5(9.3)% vs. 49.4 ± = (10.9)%; p = 0.904). The within-subject change in ECV varied markedly (1.0% (20.0%)). In multiple linear regression, TIMI coronary flow grade 2 pre-PCI, TIMI coronary flow grade 3 pre-PCI, a history of previous PCI and initial infarct size were independently associated with%ΔECV (all p Conclusion %ΔECV is associated with measures of MI severity, and portends worsening LV volume. Infarct ECV represents a novel biomarker for infarct characterisation in STEMI patients.

Background Myocardial extracellular volume (ECV) can be estimated by cardiac magnetic resonance imaging (CMR). The age- and sex- associations with ECV in healthy mid-life adults are uncertain. Methods Healthy adults with no cardiovascular disease underwent CMR at 1.5 Tesla (Siemens MAGNETOM Avanto). T1 mapping with MOLLI was performed before and 15-minutes after contrast (0.15 mmol/kg gadoterate meglumin). ECV was estimated in regions (AHA 16-segment model). ECV was calculated as the difference in relaxation rate (R1 = 1/T1) for myocardium and LV blood pool before vs. after gadolinium contrast administration, corrected for haematocrit (HCT). LV segments which were not evaluable due to artefact were excluded from analysis. Results 120 segments were assessed from 20 subjects (mean age 61 ± 12 years; 11 (55%) male). 23(19%) segments were excluded due to artefact. The remaining segments for each subject were averaged to give an overall ECV (global LV). The mean (SD) ECV for all subjects was 22.2(3.1)%. ECV in females was higher than in males (24.4(3.2)% vs. 20.4(1.4)%; P = 0.006). Overall, ECV was negatively correlated with age (r = –0.455, P = 0.044), however, the correlation was sex-dependent (women: r = –0.666, P = 0.050; men: r = –0.131, P = 0.702). There was a statistically significant interaction between age and sex when assessed using linear regression (P = 0.029). Conclusion Myocardial ECV is higher in women than in men. ECV is negatively correlated with age in women but not in men. The sex difference became less apparent with increasing age, implying that menopausal changes may be relevant. This possibility merits further assessment in a larger population.

Background The clinical significance of extracellular volume (ECV) in remote myocardium post-STEMI has not been fully studied. Myocardial ECV can be estimated by cardiac magnetic resonance imaging (CMR). The aim of this study was to assess remote ECV and its changes over time in acute STEMI survivors. Methods STEMI survivors were enrolled in a cohort study (BHF MR-MI – [NCT02072850][1]). CMR was performed at 1.5 Tesla (Siemens MAGNETOM Avanto) 2 days and 6 months post-MI. T1 MOLLI mapping was performed pre- and 15 min post-contrast (0.15 mmol/kg gadoterate meglumin). ECV was calculated as the difference in relaxation rate (R1 = 1/T1) for myocardium and left ventricular (LV) blood pool pre- vs. post-contrast, corrected for haematocrit (HCT). Associations were assessed between remote zone ECV and LV end-diastolic volume (LVEDV) as a measure of ventricular remodelling. Results 140 patients (59 ± 11 years; 107 (76%) male) were enrolled. Remote ECV at baseline and follow-up was 22.4(3.0)% and 22.5(2.9)%, respectively (p = 0.644). At 6 months, LVEDV increased by 2(25) ml. Remote zone ECV was not associated with follow-up LVEDV or change in LVEDV. In a subgroup analysis, remote zone ECV at 2 days was associated with LVEDV at follow up in patients without CMR evidence of early microvascular obstruction (MVO) (–1.44 (–2.76, –0.12); p = 0.033; n = 53), but not those with MVO (n = 78). Similarly, remote zone ECV was associated with change in LVEDV in patients without MVO. Conclusion In acute STEMI survivors, the presence of MVO is an influence on the relationship between remote zone ECV and left ventricular outcome. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02072850&atom=%2Fheartjnl%2F101%2FSuppl_6%2FA4.3.atom

Background The success of emergency coronary reperfusion therapy in ST-elevation myocardial infarction (STEMI) is commonly limited by failed tissue perfusion. Purpose To assess the clinical significance of myocardial haemorrhage using cardiac magnetic resonance (CMR) in survivors of acute STEMI and assess the temporal evolution of intramyocardial haemorrhage (IMH) versus microvascular obstruction (MVO) in a serial imaging subset. Methods 286 reperfused STEMI patients underwent CMR 2-days and 6-months post-MI. IMH was taken to represent a hypointense infarct core with a T2* value Results 245 STEMI patients had evaluable T2* data and 101 (41%) patients had IMH. 133 (51%) patients had MVO. All of the patients with IMH had MVO. IMH was multivariably associated with adverse remodelling, independent of baseline LVEDV (OR (95% CI): 2.64 (1.07, 6.49); p = 0.035). IMH was also multivariably associated with CVD/HF post-discharge (HR (95% CI): 12.9 (1.6, 100.8); p = 0.015). In the serial imaging subgroup, IMH occurred in 7(23%), 13(43%), 11(33%), and 4(13%) patients at 4–12 h, 3-days, 10-days and 7-months, respectively. The amount of MVO was greatest 4–12 h post-reperfusion, then fell progressively over time. In contrast, the amount of IMH increased dynamically from 4–12 h with a peak at 3 days. MVO resolved by day 10 in 8 patients (44%), 2 (25%) of whom had IMH. Whereas MVO persisted in 10 patients (56%), all (100%) of whom had IMH. Conclusion IMH is independently associated with adverse remodelling and ACD/HF post-discharge. T2* imaging differentiates persistent, structural microvascular destruction from functional, potentially reversible MVO. IMH is a biomarker with potential to reflect the efficacy of therapeutic interventions in STEMI patients.

Background Myocardial extracellular volume (ECV) can be estimated by cardiac magnetic resonance imaging (CMR) using pre- and post-contrast T1 MOLLI maps. The age and sex associations with myocardial ECV in healthy mid-life adults are uncertain. Methods Healthy adults without any history of cardiovascular disease or treatment underwent contrast-enhanced CMR at 1.5 Tesla (Siemens MAGNETOM Avanto). T1 mapping with MOLLI was performed before and 15 min after contrast (0.15 mmol/kg gadoterate meglumine). ECV was estimated in regions (AHA 16-segment LV model) and for the whole left ventricular (LV) myocardium (all regions). ECV was calculated as the difference in relaxation rate (R1=1/T1) for myocardium and LV blood pool before vs. after gadolinium contrast administration, corrected for haematocrit (HCT). LV segments which were not evaluable due to artefact were excluded from analysis. Results 114 segments were assessed from 19 subjects (mean age 61 ± 12 years; 10 (53%) male). 21 (18%) segments were excluded due to blood pool artefact or signal drop-out in the pre-contrast T1 MOLLI scan. All segments were evaluable in the post-contrast T1 MOLLI scans. The remaining segments for each subject were averaged to give an overall ECV (global LV). The mean ECV for all subjects was 25.6 ± 2.9%. There was no overall segmental variation in ECV. ECV in females was higher than in males (27.6 ± 3.1% vs. 23.9 ± 1.3%; P = 0.003) The percentage difference was 14.5%. ECV was higher in septal segments in females (anteroseptal: 28.0 ± 3.3% vs. 24.2 ± 1.5%; P = 0.004; inferoseptal: 27.3 ± 3.8% vs. 23.5 ± 1.6%; P = 0.011), whereas no differences were observed for other segments (Table 1). Conclusion In this preliminary analysis, myocardial ECV was higher in women than in men, which was attributable to higher ECV in the septum in females. This sex difference merits further study. If these results are confirmed by other studies, then sex-specific reference ranges for ECV would seem appropriate.

Background The clinical significance of extracellular volume (ECV) expansion in infarcted myocardium post-STEMI is unknown. Myocardial ECV can be estimated by cardiac magnetic resonance imaging (CMR) using T1 MOLLI maps before and after contrast. We repeatedly measured infarct ECV in STEMI survivors, and assessed the relationships between ECV, peak troponin T and baseline infarct size. Methods Acute STEMI survivors were enrolled in a single-centre cohort study (BHF MR-MI study – NCT02072850). Contrast-enhanced CMR was performed at 1.5 Tesla (Siemens MAGNETOM Avanto) 2 days and 6 months post-MI. T1 mapping with MOLLI was performed before and 15 min after contrast (0.15 mmol/kg gadoterate meglumine). ECV analysis was performed by outlining regions of interest (ROIs) in infarcted myocardium and left ventricular (LV) blood pool. ROIs were representative of the infarct including microvascular obstruction. ECV was calculated as the relaxation rate (R1=1/T1) for myocardium and LV blood pool before vs. after contrast, corrected for haematocrit. Infarct size was measured using late gadolinium images and expressed as a percentage of LV mass. Infarct ECV at baseline and follow up was compared with peak troponin T measured at presentation and infarct size at baseline. Peak troponin T was log-transformed to improve normality and linearity. Results 201 STEMI patients (mean age 58 ± 11 years; 156 (77%) male) were enrolled. Infarct ECV was similar at baseline and follow-up (51.3 ± 9.5% vs. 50.3 ± 12.0%, p = 0.097). Peak troponin T was widely variable (4256.7 ug/L ± 4020.8 ug/L). Peak troponin T was positively associated with infarct ECV at baseline (p Conclusion High peak troponin T and a large infarct size are predictors of higher infarct ECV at baseline and follow-up. Infarct ECV is associated with clinical and MRI measures of MI severity in survivors of STEMI.

Background:\ud Myocardial transverse relaxation time (T2, ms) is a fundamental magnetic property of tissue that is related to water content and mobility. The pathophysiological and prognostic importance of native myocardial T2 in acute ST-elevation myocardial infarction (STEMI) patients is unknown. We aimed to assess the clinical significance of native T2 within the infarct core using cardiac magnetic resonance (CMR) imaging.\ud \ud Methods:\ud We performed a prospective single center cohort study in reperfused STEMI patients who underwent CMR 2 days and 6 months post-MI. T2-weighted CMR (investigational prototype T2-prepared TrueFisp sequence) was measured in myocardial regions-of-interest. The infarct territory and microvascular obstruction were depicted with late gadolinium enhancement CMR. All-cause death or heart failure hospitalization was a pre-specified outcome that was assessed during follow-up.\ud \ud Results:\ud 324 STEMI patients (mean±SD age 59±12 years, 237 males, 121 with anterior STEMI) gave informed consent and had CMR (14 July 2011 - 22 November 2012). All 324 had follow-up assessments (median duration 860 days). Infarct size was 18 ±14% of LV mass. One hundred and sixty four (51%) patients had late microvascular obstruction whereas 197 (61%) patients had an infarct core revealed by native T2. Native T2 within the infarct core (53.9±4.8) was higher than in the remote zone (49.7±2.1 ms; p

Background:\ud The pathophysiology and prognostic significance of remote myocardium in the natural history of STEMI is uncertain. Cardiac magnetic resonance (CMR) provides a non-invasive assessment of myocardial pathology that is spatially and temporally coordinated. Native T1 quantified by CMR (T1 relaxation time, milliseconds) is a fundamental tissue property determined by water content and cellularity. We aimed to investigate the clinical significance of remote myocardium in survivors of acute ST-elevation myocardial infarction (STEMI) using native T1 mapping.\ud \ud Methods:\ud We performed a prospective single center cohort study in reperfused STEMI patients who underwent CMR 2 days and 6 months post-MI and long term follow-up (18 months minimum). Native T1 CMR (MOLLI investigational prototype sequence: 3 (3) 3 (3) 5) was measured in regions-of-interest in remote and injured myocardium. Infarction was depicted on late gadolinium contrast enhancement imaging. Adverse remodeling was defined as an increase in left ventricular end-diastolic volume ≥ 20% at 6 months. Major adverse cardiac events (MACE) were defined as cardiac death or hospitalization for non-fatal MI or heart failure. Results are mean±SD unless specified.\ud \ud Results:\ud 300 STEMI patients (mean age 59 years, 74% male) gave informed consent (14 July 2011 - 21 November 2012). Of these, 288 STEMI patients had evaluable native T1 CMR and follow-up data (median duration 845 days). Infarct size was 18±14% of left ventricular mass. Two days post-STEMI, native T1 in remote myocardium was lower than native T1 in the infarct zone (961±25 ms vs. 1097±52 ms; p

Introduction In primary percutaneous coronary intervention (PCI) for ST elevation myocardial infarction (STEMI), no-reflow after stenting may cause heart failure acutely and in the longer term. Currently there are no evidence-based treatments for no-reflow. We hypothesised that after initial myocardial reperfusion, deferring stent implantation for a limited period of time might reduce no-reflow and its sequelae compared to usual care with immediate stenting. Methods A prospective randomised controlled trial in consecutive STEMI patients (NCT01717573). Patients with risk factors for no-reflow (eg, occluded artery (TIMI 0/1), heavy thrombus burden (TIMI 2+ thrombus grade)) were eligible if TIMI 3 coronary flow had been established by initial aspiration thrombectomy and/or balloon angioplasty. Randomisation was performed electronically to deferred stenting (4–16 h later) or usual care with immediate stenting. Deferred patients received intravenous tirofiban and subcutaneous enoxaparin during the period between randomisation and stenting. All patients received oral dual antiplatelet therapy. The primary end-point was the incidence of no-reflow, defined as the occurrence of TIMI 0/1 flow post stenting. Contrast-enhanced cardiac MRI was performed 2 days post-MI and all patients had prospective follow-up. The angiograms and clinical events were independently adjudicated. Results Of 451 consecutive STEMI patients treated in our centre (11 March–22 November 2012), 101 patients (mean±SD age 60±12 years; 69% male, 13% diabetes, 7% previous MI) were randomised (n=52 to deferred stenting, n=49 immediate stenting). The clinical characteristics were similar in each group. In the deferred stent group, the median (IQR) time to deferred stenting was 8 (6, 11) hours. Compared with usual care with immediate stenting, no-reflow was significantly less frequent in the deferred stenting group: 0.0% versus 10% (p=0.005). Intra-procedural thrombotic events (IPTEs) were also less frequent with deferred stenting: 14% versus 41% (p=0.003). Contrast-enhanced MRI disclosed microvascular obstruction in 59% of patients in the immediate stenting group and 44% in the deferred stenting group (p=0.36). Killip class III heart failure occurred in two patients in the deferred stent group and in one patient in the immediately stented group. Recurrent MI Conclusions For the first time we have found that a strategy of deferred stenting in selected patients reduced no-reflow and IPTEs in primary PCI. Our intervention is pragmatic and potentially widely applicable. Our results support the rationale for a multicentre trial to assess the safety and cost-effectiveness of deferred stenting in primary PCI.