Prathap Kanagala

Intertechnique agreement and interstudy reproducibility of strain and diastolic strain rate at 1.5 and 3 Tesla: a comparison of feature-tracking and tagging in patients with aortic stenosis.

To determine the interstudy reproducibility of myocardial strain and peak early‐diastolic strain rate (PEDSR) measurement on cardiovascular magnetic resonance imaging (MRI) assessed with feature tracking (FT) and tagging, in patients with aortic stenosis (AS).

Comparison of cardiovascular magnetic resonance feature tracking and tagging for the assessment of left ventricular systolic strain in acute myocardial infarction

AIMS To assess the feasibility of feature tracking (FT)-measured systolic strain post acute ST-segment elevation myocardial infarction (STEMI) and compare strain values to those obtained with tagging. METHODS Cardiovascular MRI at 1.5T was performed in 24 patients, 2.2 days post STEMI. Global and segmental circumferential (Ecc) and longitudinal (Ell) strain were assessed using FT and tagging, and correlated with total and segmental infarct size, area at risk and myocardial salvage. RESULTS All segments tracked satisfactorily with FT (p<0.001 vs. tagging). Total analysis time per patient was shorter with FT (38.2±3.8 min vs. 63.7±10.3 min, p<0.001 vs. tagging). Global Ecc and Ell were higher with FT than with tagging, apart from FT Ecc using the average of endocardial and epicardial contours (-13.45±4.1 [FT] vs. -13.85±3.9 [tagging], p=0.66). Intraobserver and interobserver agreement for global strain were excellent for FT (ICC 0.906-0.990) but interobserver agreement for tagging was lower (ICC<0.765). Interobserver and intraobserver agreement for segmental strain was good for both techniques (ICC>0.7) apart from tagging Ell, which was poor (ICC=0.15). FT-derived Ecc significantly correlated with total infarct size (r=0.44, p=0.03) and segmental infarct extent (r=0.44, p<0.01), and best distinguished transmurally infarcted segments (AUC 0.77) and infarcted from adjacent and remote segments. FT-derived Ecc correlated strongest with segmental myocardial salvage (rs=-0.406). CONCLUSIONS FT global Ecc and Ell measurement in acute STEMI is feasible and robust. FT-derived strain is quicker to analyse, tracks myocardium better, has better interobserver variability and correlated more strongly with infarct, area at risk (oedema), myocardial salvage and infarct transmurality.

Comparison of semi-automated methods to quantify infarct size and area at risk by cardiovascular magnetic resonance imaging at 1.5T and 3.0T field strengths.

BackgroundThere is currently no gold standard technique for quantifying infarct size (IS) and ischaemic area-at-risk (AAR [oedema]) on late gadolinium enhancement imaging (LGE) and T2-weighted short tau inversion recovery imaging (T2w-STIR) respectively. This study aimed to compare the accuracy and reproducibility of IS and AAR quantification on LGE and T2w-STIR imaging using Otsu’s Automated Technique (OAT) with currently used methods at 1.5T and 3.0T post acute ST-segment elevation myocardial infarction (STEMI).MethodsTen patients were assessed at 1.5T and 10 at 3.0T. IS was assessed on LGE using 5–8 standard-deviation thresholding (5-8SD), full-width half-maximum (FWHM) quantification and OAT. AAR was assessed on T2w-STIR using 2SD and OAT. Accuracy was assessed by comparison with manual quantification. Interobserver and intraobserver variabilities were assessed using Intraclass Correlation Coefficients and Bland-Altman analysis. IS using each technique was correlated with left ventricular ejection fraction (LVEF).ResultsFWHM and 8SD-derived IS closely correlated with manual assessment at both field strengths (1.5T: 18.3 ± 10.7% LV Mass [LVM] with FWHM, 17.7 ± 14.4% LVM with 8SD, 16.5 ± 10.3% LVM with manual quantification; 3.0T: 10.8 ± 8.2% LVM with FWHM, 11.4 ± 9.0% LVM with 8SD, 11.5 ± 9.0% LVM with manual quantification). 5SD and OAT overestimated IS at both field strengths. OAT, 2SD and manually quantified AAR closely correlated at 1.5T, but OAT overestimated AAR compared with manual assessment at 3.0T. IS and AAR derived by FWHM and OAT respectively had better reproducibility compared with manual and SD-based quantification. FWHM IS correlated strongest with LVEF.ConclusionsFWHM quantification of IS is accurate, reproducible and correlates strongly with LVEF, whereas 5SD and OAT overestimate IS. OAT accurately assesses AAR at 1.5T and with excellent reproducibility. OAT overestimated AAR at 3.0T and thus cannot be recommended as the preferred method for AAR quantification at 3.0T.

Inter-study reproducibility of circumferential strain and strain rates at 1.5T and 3T: a comparison of tagging and feature tracking

Background Feature Tracking (FT) is a relatively new technique for measuring strain on cardiac magnetic resonance imaging (CMR), that has been shown to have reasonable interstudy reproducibility (Coefficient of variation (CoV) ~20%) in healthy volunteers. The inter-study reproducibility of FT has not yet been reported in any patient groups, nor compared to that of MRI tagging. We sought to determine the inter-study reproducibility of circumferential strain and strain rates using FT and tagging at 1.5T and 3T scanners, in patients with moderate-severe Aortic Stenosis (AS). Methods CMR was performed twice in 8 patients with severe AS on a 1.5T scanner and 10 patients with moderate-severe AS at 3T. Three short-axis tagged images were acquired, in addition to the standard SSFP short-axis cine stack. InTag (Creatis, Lyon, France) in OsiriX (Geneva, Switzerland) was used to calculate the Circumferential Peak Systolic Strain (PSS), Peak Systolic Strain Rate (PSSR) and Peak Early Diastolic Strain Rate (PEDSR). Diogenes CMR FT (TomTec Imaging Systems, Munich, Germany) was used to calculate the same parameters on nearest SSFP cine images. Results Overall, FT gave higher strain and strain rate values when compared to tagging. On paired sample t-tests, there was no significant difference in the strain and strain rate values between scan one and scan two, using both tagging and FT, at both 1.5T and 3T. The inter-study reproducibility of both techniques was higher at 1.5T compared to 3T. (Table 1, Figure 1) Comparing tagging vs FT, PSS was more reproducible with FT at both 1.5T and 3T, while PSSR was more reproducible with tagging. PEDSR demonstrated similar inter-study reproducibility using both techniques, but was much more reproducible at 1.5T than 3T. (CoV’s for circumferential PSS, PSSR and PEDSR at 1.5T- FT: 8.6, 11.8 and 13.1%, tagging: 12.2, 9.4 and 17.5%; CoV’s at 3T-FT: 9.4, 23 and 25.6%, tagging: 17.9, 19.3 and 32.5%). Conclusions Both tagging and FT have good reproducibility at 1.5T and modest reproducibility at 3T scanners. This may partly be due to greater artefacts at 3T. Overall, FT appears to have higher reproducibility than tagging for circumferential PSS, while PSSR is more reproducible with tagging. If the main parameter of interest is PEDSR, scanning at 1.5T and using FT is more preferable. Given that FT does not require additional image acquisitions and involves shorter post-processing time, this technique is likely to become the preferred method for strain and strain rate quantification with CMR.

131 Comparison of Semi-automated Methods to Quantify Infarct Size and Myocardial Salvage by Cardiac MRI at 1.5T and 3.0T Field Strengths

Introduction There is no consensus on the optimal method of quantifying infarct size (IS) on late gadolinium imaging (LGE) or area at risk (oedema, [AAR]) on T2-weighted STIR (T2wSTIR) in patients with ST-segment elevation myocardial infarction (STEMI).Semi-automated standard deviation (SD) based techniques, manual contouring of enhancement, and full-width half-maximum (FWHM) methods are used. Otsu’s Automated Thresholding (OAT) automatically identifies areas of enhancement by selecting the signal intensity threshold giving minimal intraclass variance within enhanced and normal myocardium and is user-independent.There are only 2 published studies using OAT quantification, of IS and AAR. There are no published studies using OAT at 3.0T, of reproducibility of OAT-based AAR or using OAT to calculate MSI. We aimed to compare the accuracy and reproducibility of IS, AAR and myocardial salvage index (MSI) quantification on LGE and T2w-STIR imaging using OAT with currently used methods at 1.5T and 3.0T in acute STEMI. Methods Ten patients were assessed at 1.5T and 10 at 3.0T.IS was assessed on LGE using 5 standard-deviation thresholding (5SD), FWHM and OAT quantification. AAR was assessed on T2w-STIR using 2SD and OAT. Accuracy was assessed by comparison with manual quantification. Inter-observer and intra-observer variabilities were assessed using Intraclass Correlation Coefficients and Bland-Altman analysis. Results FWHM-derived IS closely correlated with manual assessment and had excellent inter-observer and intra-observer reproducibilities.5SD and OAT overestimated IS.OAT overestimated AAR and 2SD demonstrated a trend towards overestimation (Figures 1–2, below). MSI quantified using 2SD and OAT-derived AAR was similar. AAR and MSI quantification using OAT demonstrated a trend towards better reproducibility versus 2SD, which was significant at 3T. Abstract 131 Figure 1 IS and AAR (oedema) quantification Top row: IS and AAR on a patient at 3.0T showing increasing IS using FWHM, 5SD and OAT. Middle row: AAR in the same patient using OAT was greater than on 2SD thresholding at 3.0T, and was similar for patients studied at 1.5T. Bottom row: Graphs showing IS using OAT, 5SD and FWHM compared to manual quantification at 1.5T and 3.0T. Abstract 131 Figure 2 AAR (oedema) quantification AAR compared using 2SD and OAT versus manual quantification at 1.5T and 3.0T. Conclusions/Implications FWHM-based assessment of IS is accurate and reproducible, whereas 5SD and OAT overestimate IS. OAT-based assessment of AAR and MSI has similar accuracy but with a tendency towards better observer agreement compared with 2SD thresholding in acute STEMI.

Comparison of T1-mapping and T2-weighted imaging for diagnostic oedema assessment in ST-segment elevation myocardial infarction

Background Myocardial oedema (area-at-risk, AAR) is typically imaged using a pre-contrast T2-weighted short tau inversion recovery (T2w-STIR) sequence on cardiovascular magnetic resonance (CMR) imaging. However, this sequence is prone to motion and rhythm artefact, signal dropout, blood-pool artefact, surface coil signal inhomogeneity and potentially prohibitive long breath-hold duration. This susceptibility to artefacts limits utility of T2w-STIR in large clinical trials where attainment of diagnostic quality oedema imaging in the majority is necessary to determine myocardial salvage: a measure of reperfusion success and a strong predictor of adverse remodeling and prognosis post ST-segment elevation myocardial infarction (STEMI). We compare AAR quantified on T2w-STIR imaging with novel T1-mapping on 3.0T CMR post STEMI.

The many faces of HFPEF: insights from the CMR substudy of DIAMOND-HFPEF

Background Heart failure with preserved ejection fraction (HFPEF) carries significant mortality and morbidity. This population is characterized by marked heterogeneity. To date, this population has been poorly phenotyped and it remains unclear what proportion may have evidence of myocardial infarction (MI), undiagnosed cardiomyopathies or phenocopies of heart failure. At present, echocardiography remains the primary modality for diagnosis and inclusion into randomized controlled trials but can be challenging due to the high prevalence of lung disease, obesity and frailty. We sought to evaluate the impact of adding cardiac magnetic resonance imaging (CMR) to the diagnostic pathway. Methods CMR was offered as part of DIAMOND-HFPEF (Developing Imaging And plasMa biOmarkers iN Describing Heart Failure with Preserved Ejection Fraction): a prospective, observational, cohort study. Inclusion criteria were: clinical features of HF and left ventricular ejection fraction (LVEF) > 50% as per echocardiography. Exclusion criteria were: suspected or confirmed cardiomyopathy, pericardial constriction, inability to consent, noncardiovascular life expectancy < 6 months, myocardial infarction in the preceding 6 months, severe valve disease, severe obstructive pulmonary disease (or FEV1 < 30% or FVC < 50% predicted) and estimated glomerular filtration rate < 30 ml/min/m 2 . 138 eligible subjects underwent 3 T CMR (Siemens Skyra) according to a

Effect of late sodium current inhibition on MRI measured diastolic dysfunction and myocardial perfusion reserve in aortic stenosis: a pilot study

Background Aortic Stenosis (AS) is characterized by pressure overload hypertrophy (LVH) with associated diastolic dysfunction. The presence of LVH, diastolic dysfunction and microvascular dysfunction appear to be important determinants of exercise capacity in AS. There are no medical therapies in AS of proven value. Ranolazine is licenced for the treatment of angina and inhibits late sodium channel activation. Ranolazine has been shown to improve diastolic dysfunction in isolated myocytes. Methods In this prospective, open label study with blinded endpoint analysis, patients with asymptomatic moderate/severe AS and diastolic dysfunction or LVH were recruited. Patients, underwent trans-thoracic echocardiography, exercise testing and adenosine stress cardiac magnetic resonance imaging at baseline, 6 weeks after commencing Ranolazine (maximum dose 750mg BD) and again at 10 weeks (4 weeks after discontinuation). Tagged images were acquired at three short-axis slices on a 3T platform (Siemens Skyra). Myocardial perfusion reserve was calculated from stress and resting blood flow. The primary hypothesis was that Ranolazine would improve peak early diastolic strain rate (PEDSR) on tagged MRI. Results Fifteen patients (PPG 48.8±12.4 mmHg, MPG 27.1±7.5 mmHg, AVA 1.26±0.31 cm 2 , LV mass index 66.72±15.35 g/m 2 ) completed the week-6 visit and 13 completed the final visit. Results are shown in table 1. There was a trend for the global PEDSR to increase from the baseline to week-6 (0.79 ± 0.15 to 0.86 ± 0.18, p=0.198). For those who completed the final visit, PEDSR increased from baseline to week-6 and then returned close to the baseline value at week-10 (table). There was no significant change in MPR or echocardiographic measures of diastolic dysfunction. The total exercise duration increased from 10.47 ±3.68 minutes to 11.60±3.25 minutes (n=15, p=0.06), with a trend for the maximal HR and SBP to be lower at week6, resulting in a reduction in exercise LV rate-pressure product (LVRPP), suggesting improved myocardial efficiency. On splitting the patients into low and high-MPR subgroups based on the median MPR, the trend for the improvement in PEDSR (0.88 ± 0.80, 1.03 ± 0 .30, 0.86 ± 0.15) and reduction in exercise LVRPP was maintained in the low-MPR subgroup only. Conclusions This pilot hypothesis-generating study has shown some signals towards Ranolazine improving diastolic function and exercise myocardial efficiency in patients with AS, particularly in those with a lower MPR. The current results would support a larger study in patients with diastolic dysfunction. Funding

27 High definition lipoproteomics reveal dysregulated redox proteins in coronary artery disease

Background Lipoproteins have an integral role in the pathogenesis of CAD. Quantitative proteomics is evolving to become an indispensable tool in the era of precision medicine. Using an unbiased lipoproteomic discovery workflow we sought to investigate the lipoproteomic differences between stable CAD patients and controls subjects and to reveal novel pathways/mechanisms that underpin this common disease. Methods Male patients with stable CAD (n = 49, mean ± SD; age 64 yrs ± 8.69) and without CAD (n = 17; mean age 74 yrs ± 6.21) were recruited into this single centre prospective cohort study. Plasma was co-incubated with a lipophilic affinity resin. Isolated lipoproteins were reduced, alkylated, digested and analysed using label-free high definition ion mobility enabled mass spectrometry. Raw data was analysed using Progenesis QI software with a stringent false discovery rate of 1%. Results 202 proteins showed significant differential expression between the CAD patients and the control subjects (P < 0.05). CAD patients had selective depletion of antioxidants; glutathione peroxidase 3 (GPX3) (p < 1e-28), clusterin (p < 1e-12) and serum paroxonase-1 (PON1) (p < 1e-7) compared with controls. Furthermore, there was selective up-regulation of proteins concerned with inflammation; serum amyloid A-1 (p < 1e-12), mannan binding lectin serine protease 1 (MASP1) (p < 1e-8) and galectin-3-binding protein (p = 0.001) in the CAD patients compared with the control subjects. Phospholipid transfer protein (PLTP) (p < 0.001) and apolipoprotein (a) (p = 0.002) were over expressed in the CAD patients. Conclusion Patients with CAD have a distinct pathognomonic lipoproteomic cargo. The measurement of certain lipoprotein associated proteins may assist in the early identification of such patients before symptom onset.

039 PREVALENCE AND EXTENT OF INFARCT AND MICROVASCULAR OBSTRUCTION FOLLOWING A RANGE OF REPERFUSION TECHNIQUES IN ST-ELEVATION MYOCARDIAL INFARCTION (STEMI)

Introduction Cardiac MRI (CMR) provides unique characterisation of myocardial injury post acute STEMI. It is the gold standard for non-invasive measurement of Infarct Size (IS) and tissue perfusion during STEMI. Microvascular obstruction (MVO) describes suboptimal tissue perfusion despite restoration of flow in the infarct-related artery (IRA). IS and MVO are independent predictors of adverse remodelling and prognosis post STEMI. MVO is generally assumed to be related primarily to reperfusion. CMR extent of IS and MVO decreases after 48 h post STEMI. There is a dearth of data on the prevalence and extent of MVO in clinical practice using different reperfusion methods, in particular in those without reperfusion. We hypothesise that the extent and presence of MVO are primarily related to the extent of ischaemic injury rather than reperfusion injury. Table 1 Key demographics and CMR analyses in the early reperfused and non-reperfused patients Variable Total study group (n=94) Early reperfused (PPCI+lysis, n=59) Non-reperfused (n=21) P Value Age (years) 61.01±13.1 60.24±11.90 65.57±16.18 0.114 Male sex (%) 82 (87.2) 53 (89.8) 16 (76.2) 0.121 Diabetes mellitus (n, %) 9 (9.6) 3 (5.1) 6 (28.6) 0.004 Time from admission-CMR (days) 2.22 (1.24–3.79) 1.91 (1.16–2.58) 6.59 (4.77–10.97) <0.001 LVEDVI (ml/m2) 94.21 (85.55–110.98) 90.68 (82.38–102.72) 98.04 (88.12–124.97) 0.013 LVESVI (ml/m2) 55.56 (48.08–69.93) 51.35 (45.37–62.62) 61.09 (53.97–83.64) 0.004 EF (%) 39.85±9.39 42.30±7.80 35.02±11.30 0.002 IS (% LV mass) 25.41±18.37 18.85±12.65 23.07±11.37 0.181 MVO (% LV mass) 0.60 (0.00–3.10) 0.44 (0.00–2.92) 1.34 (0.00–2.79) 0.364 Mean±SD where normally distributed. Method 94 acute STEMI subjects were studied. 75 were prospectively recruited into a study of ventricular remodelling post STEMI. 19 subjects were routine clinical CMR examinations undertaken in non-reperfused, late-presenting patients (>12 h symptoms) to assess viability. Subjects were assessed on a Siemens Avanto 1.5T system. LV function and volumes were assessed using SSFP. Ten minutes after intravenous injection of gadolinium contrast (0.2 mmol/kg), delayed contrast-enhanced images were acquired using a segmented inversion-recovery gradient-echo sequence. IS was defined as areas of hyperenhancement with signal intensity (SI) >50% of peak SI in the infarct core (Full-Width Half-Maximum technique). MVO was defined as hypointensity within areas of infarct. Independent T Test and Mann-Whitney U Test analyses were used for normally and non-parametrically distributed data respectively. Statistical significance was taken at p<0.05. Results There was no significant difference in age, sex, prevalence of angina, proportion of STEMI with left anterior descending artery IRA, TIMI score or Rentrop (degree of collateralization) score in early reperfused (PCI or Thrombolysis <12 h of symptoms, n=59) and non-reperfused patients (n=21) (table 1, below). Diabetes mellitus was more prevalent in non-reperfused patients (p=0.004). LV volumes were significantly greater and ejection fraction (LVEF) was significantly lower in non-reperfused patients. Despite a longer time from admission to CMR (p<0.001), there was a trend towards greater IS and extent of MVO in non-reperfused patients. Of the 15 non-reperfused patients who had angiography, the absence of spontaneous reperfusion was confirmed in 67% (TIMI flow 0–1). χ2 Analysis showed a trend towards higher prevalence of MVO in non-reperfused STEMI (71.4% vs 55.2%). Late PCI patients (n=6) demonstrated a trend towards higher volumes and greater extent of IS and MVO compared with non-reperfused and rescue PCI (n=8) patients. No differences were seen between rescue PCI and non-reperfused patients. Conclusions The prevalence and extent of myocardial and microvascular injury (IS, MVO) on CMR in non-reperfused STEMI is at least as much as that occurring in those undergoing early reperfusion therapy. This is despite a significantly longer time to CMR in non-reperfused patients, which would be expected to result in a reduction in IS and MVO. MVO is not exclusive to reperfusion and may represent the degree of ischaemic injury. Median (25th–75th quartiles) where non-normally distributed. Total study group (n=94) consists of early reperfused, non-reperfused, late PCI and rescue PCI patients.