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Background Segmental extent of infarction assessed by late gadolinium enhancement (LGE) imaging early post‐ST‐segment elevation myocardial infarction (STEMI) has utility in predicting left ventricular functional recovery. Hypothesis: We hypothesized that segmental circumferential strain with displacement encoding with stimulated echoes (DENSE) would be a stronger predictor of infarct transmurality than feature‐tracking strain, and noninferior to extracellular volume fraction (ECV). Study Type: Prospective. Population: Fifty participants (mean ± SD, 59 ± 9 years, 40 [80%] male) underwent cardiac MRI on day 1 post‐STEMI. Field‐Strength/Sequences: 1.5T/cine, DENSE , T1 mapping, ECV , LGE. Assessment Two observers assessed segmental percentage LGE extent, presence of microvascular obstruction (MVO), circumferential and radial strain with DENSE and feature‐tracking, T1 relaxation times, and ECV. Statistical Tests: Normality was tested using the Shapiro–Wilk test. Skewed distributions were analyzed utilizing Mann–Whitney or Kruskal–Wallis tests and normal distributed data using independent t ‐tests. Diagnostic cutoff values were identified using the Youden index. The difference in area under the curve was compared using the z‐statistic. Results: Segmental circumferential strain with DENSE was associated with the extent of infarction ≥50% (AUC [95% CI], cutoff value = 0.9 [0.8, 0.9], −10%) similar to ECV (AUC = 0.8 [0.8, 0.9], 37%) (P = 0.117) and superior to feature‐tracking circumferential strain (AUC = 0.7[0.7, 0.8], −19%) (P

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.

Supplemental Digital Content is available in the text., The rationale for our study was to investigate the pathophysiology of microvascular injury in patients with acute ST-segment–elevation myocardial infarction in relation to a history of hypertension. We undertook a cohort study using invasive and noninvasive measures of microvascular injury, cardiac magnetic resonance imaging at 2 days and 6 months, and assessed health outcomes in the longer term. Three hundred twenty-four patients with acute myocardial infarction (mean age, 59 [12] years; blood pressure, 135 [25] / 79 [14] mm Hg; 237 [73%] male, 105 [32%] with antecedent hypertension) were prospectively enrolled during emergency percutaneous coronary intervention. Compared with patients without antecedent hypertension, patients with hypertension were older (63 [12] years versus 57 [11] years; P

Background Cerebral small vessel disease is a common cause of vascular cognitive impairment in older people, with no licensed treatment. Cerebral blood flow is reduced in small vessel disease. Tadalafil is a widely prescribed phosphodiesterase-5 inhibitor that increases blood flow in other vascular territories. The aim of this trial is to test the hypothesis that tadalafil increases cerebral blood flow in older people with small vessel disease. Methods/design Perfusion by Arterial Spin labelling following Single dose Tadalafil In Small vessel disease (PASTIS) is a phase II randomised double-blind crossover trial. In two visits, 7-30 days apart, participants undergo arterial spin labelling to measure cerebral blood flow and a battery of cognitive tests, pre- and post-dosing with oral tadalafil (20 mg) or placebo. Sample size: 54 participants are required to detect a 15% increase in cerebral blood flow in subcortical white matter (p

Background:\ud \ud CTX0E03 is an immortalised human neural stem-cell line from which a drug product (CTX-DP) was developed for allogeneic therapy. Dose-dependent improvement in sensorimotor function in rats implanted with CTX-DP 4 weeks after middle cerebral artery occlusion stroke prompted investigation of the safety and tolerability of this treatment in stroke patients.\ud \ud Methods:\ud \ud We did an open-label, single-site, dose-escalation study. Men aged 60 years or older with stable disability (National Institutes of Health Stroke Scale [NIHSS] score ≥6 and modified Rankin Scale score 2–4) 6–60 months after ischaemic stroke were implanted with single doses of 2 million, 5 million, 10 million, or 20 million cells by stereotactic ipsilateral putamen injection. Clinical and brain imaging data were collected over 2 years. The primary endpoint was safety (adverse events and neurological change). This trial is registered with ClinicalTrials.gov, number NCT01151124.\ud \ud Findings:\ud \ud 13 men were recruited between September, 2010, and January, 2013, of whom 11 (mean age 69 years, range 60–82) received CTX-DP. Median NIHSS score before implantation was 7 (IQR 6–8) and the mean time from stroke was 29 (SD 14) months. Three men had subcortical infarcts only and seven had right-hemisphere infarcts. No immunological or cell-related adverse events were seen. Other adverse events were related to the procedure or comorbidities. Hyperintensity around the injection tracts on T2-weighted fluid-attenuation inversion recovery MRI was seen in five patients. At 2 years, improvement in NIHSS score ranged from 0 to 5 (median 2) points.\ud \ud Interpretation:\ud \ud Single intracerebral doses of CTX-DP up to 20 million cells induced no adverse events and were associated with improved neurological function. Our observations support further investigation of CTX-DP in stroke patients.

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 Statins have been associated with later life, long-term care admission in observational studies. However, by preventing vascular events, statins may also prevent or delay admission. We wished to determine statin and long-term care admission associations in a randomised controlled trial context, and describe associations between long-term care admission and other clinical and demographic factors.\ud \ud Methods: \ud We used extended follow-up of two randomised trial populations, using national data to assign the long-term care admission outcome, and included individuals screened or recruited to two large randomised trials of pravastatin 40 mg daily—the West of Scotland Coronary Prevention Study (WOSCOPS) and the pravastatin in elderly individuals at risk of vascular disease (PROSPER) study. We described univariable and multivariable analyses of potential predictors of long-term care admission with corresponding survival curves of incident long-term care admission and analyses adjusted for competing risk.\ud \ud Results: \ud In total 11,015 (10%) of the trial participants were admitted to long-term care. There was no difference between participants in the statin or placebo arms of either trial in regard to admissions to long-term care. On multivariable analyses, independent associations with incident long-term care admission in the PROSPER trial were age (hazard ratio [HR] 1.06 per year, 95% confidence interval [CI] 1.03–1.09) and male sex (HR 0.72, 95% CI 0.53–0.99). In the WOSCOPS, age (HR 1.12 per year, 95% CI 1.10–1.13) and increasing social deprivation (HR 1.05, 95% CI 1.03–1.08) were associated with incident long-term care admission.\ud \ud Conclusion: \ud We did not demonstrate an association between historical statin use and future long-term care admission. The strongest associations with incident long-term care admission were non-modifiable factors of age, sex and socioeconomic deprivation.

Supplemental Digital Content is available in the text., The natural history and pathophysiological significance of tissue remodeling in the myocardial remote zone after acute ST-elevation myocardial infarction (STEMI) is incompletely understood. Extracellular volume (ECV) in myocardial regions of interest can now be measured with cardiac magnetic resonance imaging. Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI [British Heart Foundation Magnetic Resonance Imaging in Acute ST-Segment Elevation Myocardial Infarction study]). Cardiac magnetic resonance was performed at 1.5 Tesla at 2 days and 6 months post STEMI. T1 modified Look-Locker inversion recovery mapping was performed before and 15 minutes after contrast (0.15 mmol/kg gadoterate meglumine) in 140 patients at 2 days post STEMI (mean age: 59 years, 76% male) and in 131 patients at 6 months post STEMI. Remote zone ECV was lower than infarct zone ECV (25.6±2.8% versus 51.4±8.9%; P

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 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 Infarct size assessed early after acute ST-segment elevation myocardial infarction (STEMI) can overestimate the true extent of infarction, limiting its usefulness as a prognostic biomarker. Myocardial strain derived from displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance (CMR) provides information on myocardial contractility with high precision and accuracy. We hypothesised that the prognostic value of peak circumferential strain is higher than infarct size. Methods In a prospective, single centre study, participants underwent 1·5T CMR 2 days and 6 months after myocardial infarction. The 5-SD technique was used to quantify late gadolinium enhancement (LGE) as proportion of left ventricular mass. Mid-left ventricular DENSE acquisitions were analysed using postprocessing software. During longer-term follow-up, major adverse cardiac events (MACE) were independently assessed by masked cardiologists. Participants provided written informed consent and ethics approval was given (reference 10/S0703/28). This study is registered with ClinicalTrials.gov, number NCT02072850. Findings 300 patients underwent CMR (mean age 58·6 years [SD 13·2], 237 men [79%], 118 anterior myocardial infarction [39%], 30 with diabetes [10%], 284 with normal flow [Thrombolysis in Myocardial Infarction grade 3] after percutaneous coronary intervention [95%]). 259 of these patients had DENSE acquired, of whom 21 (8%) experienced a MACE at 3 years' follow-up. DENSE and baseline LGE had reasonable power for prediction of adverse events (area under the curve [AUC] DENSE 0·712, p=0·001; AUC LGE 0·644, p=0·028). For MACE (receiver operating characteristic analysis), optimal cut-offs for peak circumferential strain using DENSE was −10·51%, and LGE 24·05 g. Cox-regression analysis showed that DENSE (hazard ratio 1·175, 95% CI 0·036–1·334; p=0·012) offered an incremental prognostic benefit over LGE (1·040, 1·010–1·070; p=0·008) to predict MACE. Interpretation DENSE-derived peak circumferential strain offers an incremental prognostic benefit over infarct size revealed by LGE to predict MACE; a cut-off of −10·51% can identify STEMI patients at higher risk of events. This is the first time, to our knowledge, that CMR-derived strain has been shown to provide prognostic utility in patients with STEMI. Funding This research was supported by project grants from the Chief Scientist Office (SC01), Medical Research Scotland (343 FRG), and the British Heart Foundation (BHF-PG/14/64/31043).

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 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.

e22512Background: Imatinib is the treatment of choice for GIST. Previous studies suggest that trough concentration (Cmin) of more than 1.1mg/L achieve better outcomes and that Cmin correlates with ...

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.

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 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.