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Background Cardiac diffusion tensor imaging (cDTI) allows for in vivo characterization of myocardial microstructure. In cDTI, mean diffusivity and fractional anisotropy (FA)-markers of magnitude and anisotropy of diffusion of water molecules-are known to change after myocardial infarction. However, little is known about regional changes in helix angle (HA) and secondary eigenvector angle (E2A), which reflects orientations of laminar sheetlets, and their association with long-term recovery of left ventricular ejection fraction (LVEF). Purpose To assess serial changes in cDTI biomarkers in participants following ST-segment elevation myocardial infarction (STEMI) and to determine their associations with long-term left ventricular remodeling. Materials and Methods In this prospective study, 30 participants underwent cardiac MRI (3 T) after STEMI at 5 days and 3 months after reperfusion (National Institute of Health Research study no. 33963 and Research Ethics no. REC17/YH/0062). Spin-echo cDTI with second-order motion-compensation (approximate duration, 13 minutes; three sections; 18 noncollinear diffusion-weighted scans with b values of 100 sec/mm2 [three acquisitions], 200 sec/mm2 [three acquisitions], and 500 sec/mm2 [12 acquisitions]), functional images, and late gadolinium enhancement images were obtained. Multiple regression analysis was used to assess associations between acute cDTI parameters and 3-month LVEF. Results Acutely infarcted myocardium had reduced FA, E2A, and myocytes with right-handed orientation (RHM) on HA maps compared with remote myocardium (mean remote FA = 0.36 ± 0.02 [standard deviation], mean infarcted FA = 0.25 ± 0.03, P < .001; mean remote E2A = 55° ± 9, mean infarcted E2A = 49° ± 10, P < .001; mean remote RHM = 16% ± 6, mean infarcted RHM = 9% ± 5, P < .001). All three parameters (FA, E2A, and RHM) correlated with 3-month LVEF (r = 0.68, r = 0.59, and r = 0.53, respectively), with acute FA being independently predictive of 3-month LVEF (standardized β = 0.56, P = .008) after multivariable analysis adjusting for factors, including acute LVEF and infarct size. Conclusion After ST-segment elevation myocardial infarction, diffusion becomes more isotropic in acutely infarcted myocardium as reflected by decreased fractional anisotropy. Reductions in secondary eigenvector angle suggest that the myocardial sheetlets are unable to adopt their usual steep orientations in systole, whereas reductions in myocytes with right-handed orientation on helix angle maps are likely reflective of a loss of organization among subendocardial myocytes. Correlations between these parameters and 3-month left ventricular ejection fraction highlight the potential clinical use of cardiac diffusion tensor imaging after myocardial infarction in predicting long-term remodeling. © RSNA, 2021 Online supplemental material is available for this article.

RNA binding motif 20 (RBM20) cardiomyopathy has been detected in approximately 3% of populations afflicted with dilated cardiomyopathy (DCM). It is well conceived that RBM20 cardiomyopathy is provoked by titin isoform switching in combination with resting Ca2+ leaking. In this study, we characterized the cardiac function in Rbm20 knockout (KO) rats at 3‐, 6‐, 9‐, and 12‐months of age and examined the effect of the ryanodine receptor stabilizer S107 on resting intracellular levels and cardiomyocyte contractile properties. Our results revealed that even though Rbm20 depletion promoted expression of larger titin isoform and reduced myocardial stiffness in young rats (3 months of age), the established DCM phenotype required more time to embellish. S107 restored elevated intracellular Ca2+ to normal levels and ameliorated cardiomyocyte contractile properties in isolated cardiomyocytes from 6‐month‐old Rbm20 KO rats. However, S107 failed to preserve cardiac homeostasis in Rbm20 KO rats at 12 months of age, unexpectedly, likely due to the existence of multiple pathogenic mechanisms. Taken together, our data suggest the therapeutic promises of S107 in the management of RBM20 cardiomyopathy., Loss of Rbm20 results in reduced myocardial stiffness at younger age and overt RBM20 cardiomyopathy at older age in rats. The RyR2 stabilizer S107 improves contractility properties by restoring the elevated resting intracellular Ca2+ level in Rbm20‐depleted cardiomyocytes. S107 could be a component of a therapeutic option for RBM20 cardiomyopathy.

Background Percutaneous mitral valve leaflet repair can be an effective treatment for primary mitral regurgitation (MR) patients deemed high-risk for surgery. Accurate assessment of cardiac reverse remodelling is essential to optimise future patient selection. Cardiovascular magnetic resonance (CMR) is the reference standard for cardiac volumetric assessment and compared to transthoracic echocardiography (TTE) provides superior reproducibility in MR quantification. Prior CMR studies have analysed cardiac reverse remodelling following percutaneous intervention in combined cohorts of primary and secondary MR patients. However, as aetiology of MR can significantly impact outcomes, focused studies are warranted. Therefore, we aimed to assess cardiac reverse remodelling and quantify changes in MR following percutaneous mitral valve leaflet repair for primary MR using the reference standard (CMR). Methods 12 patients with at least moderate-severe MR on TTE were prospectively recruited to undergo CMR imaging and 6-minute walk tests (6MWT) at baseline and 6 months following percutaneous mitral valve leaflet repair (MitraClip). CMR protocol involved: left-ventricular (LV) short axis cines (bSSFP, SENSE-2, 10mm, no gap), transaxial right-ventricular (RV) cines (bSSFP, SENSE-2, 8mm, no gap), two and four chamber cines and aortic through-plane phase contrast imaging, planned at the sino-tubular junction. MR was quantified indirectly using LV and aortic stroke volumes. Results 12 patients underwent percutaneous mitral valve leaflet repair (MitraClip) for posterior mitral valve leaflet prolapse, however 1 patient declined follow up after single-leaflet clip detachment resulting in 11 patients (age 83±5years, 9 male) completing follow up imaging. At 6-months: significant improvements occurred in New York Heart Association functional class and 6MWT distances (223±71m to 281±65m, p=0.005) (table 1) and significant reductions occurred in indexed left ventricular end-diastolic volumes (LVEDVi) (118±21ml/m2 to 94±27ml/m2, p=0.001), indexed left ventricular end-systolic volumes (58±19ml/m2 to 48±21ml/m2, p=0.007) and quantitated MR volume (55±22ml to 24±12ml, p=0.003) and MR fraction (49±9.4% to 29±14%, p≤0.001) (table 2). There were no statistically significant changes in left ventricular ejection fraction (LVEF), right ventricular dimensions/ejection fraction or bi-atrial dimensions (table 2). All patients demonstrated decreased LVEDVi and quantified MR (figure 1). Conclusion Successful percutaneous mitral valve leaflet repair for primary MR results in reduction in MR, positive LV reverse remodelling, preservation of LVEF, and functional improvements. Larger CMR studies are now required to further guide optimal patient selection. Conflict of Interest Nil

Funding Acknowledgements Type of funding sources: None. Background Percutaneous mitral valve leaflet repair can be an effective treatment for primary mitral regurgitation (MR) patients deemed high-risk for surgery. Accurate assessment of cardiac reverse remodelling is essential to optimise future patient selection. Cardiovascular magnetic resonance (CMR) is the reference standard for cardiac volumetric assessment and compared to transthoracic echocardiography (TTE) provides superior reproducibility in MR quantification. Prior CMR studies have analysed cardiac reverse remodelling following percutaneous intervention in combined cohorts of primary and secondary MR patients. However, as aetiology of MR can significantly impact outcomes, focused studies are warranted. Purpose Assess cardiac reverse remodelling and quantify changes in MR following percutaneous mitral valve leaflet repair for primary MR using the reference standard (CMR). Methods 12 patients with at least moderate-severe MR on TTE were prospectively recruited to undergo CMR imaging and 6-minute walk tests (6MWT) at baseline and 6 months following percutaneous mitral valve leaflet repair (MitraClip). CMR protocol involved: left-ventricular (LV) short axis cines (bSSFP, SENSE-2, 10mm, no gap), transaxial right-ventricular (RV) cines (bSSFP, SENSE-2, 8mm, no gap), two and four chamber cines and aortic through-plane phase contrast imaging, planned at the sino-tubular junction. MR was quantified indirectly using LV and aortic stroke volumes. Results 12 patients underwent percutaneous mitral valve leaflet repair (MitraClip) for posterior mitral valve leaflet prolapse, however 1 patient declined follow up after single-leaflet clip detachment resulting in 11 patients (age 83 ± 5years, 9 male) completing follow up imaging. At 6-months: significant improvements occurred in New York Heart Association functional class (Table 1) and 6MWT distances (223 ± 71m to 281 ± 65m, p = 0.005) and significant reductions occurred in indexed left ventricular end-diastolic volumes (LVEDVi) (118 ± 21ml/m2 to 94 ± 27ml/m2, p = 0.001), indexed left ventricular end-systolic volumes (58 ± 19ml/m2 to 48 ± 21ml/m2, p = 0.007) and quantitated MR volume (55 ± 22ml to 24 ± 12ml, p = 0.003) and MR fraction (49 ± 9.4% to 29 ± 14%, p= Conclusion Successful percutaneous mitral valve leaflet repair for primary MR results in reduction in MR, positive LV reverse remodelling, preservation of LVEF, and functional improvements. Larger CMR studies are now required to further guide optimal patient selection.

Funding Acknowledgements Type of funding sources: None. Background Long-term right ventricular (RV) pacing leads to heart failure or a decline in left ventricular (LV) function in up to a fifth of patients. Objectives We aimed to establish whether patients with focal fibrosis detected on late gadolinium enhancement cardiovascular magnetic resonance (CMR) have deterioration in LV function after RV pacing. Methods We recruited 110 patients (84 in final analysis) into two observational CMR studies. Patients (n = 34) with a dual chamber device and preserved atrioventricular (AV) conduction underwent CMR in two asynchronous pacing modes (AOO & DOO) to compare intrinsic conduction with RV pacing. Patients (n = 50) with high-grade AV block underwent CMR before and 6 months after pacemaker implantation to investigate the long-term effects of RV pacing. Results: The three key findings were 1) Initiation of RV pacing in patients with fibrosis, compared to those without, was associated with greater immediate changes in both LV end-systolic volume index (LVESVi) (5.3 ± 3.5 vs 2.1 ± 2.4 mL/m2; p Conclusions Fibrosis detected on CMR is associated with immediate and long-term deterioration in LV function following RV pacing and could be used to identify those at risk of heart failure prior to pacemaker implantation. Characteristics before and after pacing Study 1 No fibrosis (n = 16) Fibrosis (n = 18) AOO DOO p-value AOO DOO p-value LVEDVi - mL/m² 66 ± 13 66 ± 12 0.67 78 ± 14 79 ± 13 0.34 LVESVi - mL/m² 30 ± 10 32 ± 9 0.003 38 ± 11 43 ± 12

BACKGROUND: Cardiovascular magnetic resonance (CMR) image acquisition techniques during exercise typically requires either transient cessation of exercise or complex post-processing, potentially compromising clinical utility. We evaluated the feasibility and reproducibility of a navigated image acquisition method for ventricular volumes assessment during continuous physical exercise. METHODS: Ten healthy volunteers underwent supine cycle ergometer (Lode) exercise CMR on two separate occasions using a free-breathing, multi-shot, navigated, balanced steady-state free precession cine pulse sequence. Images were acquired at 3-stages, baseline and during steady-state exercise at 55% and 75% maximal heart rate (HR(max)), based on a prior supine cardiopulmonary exercise test. Intra-and inter-observer variability and inter-scan reproducibility were derived. Clinical feasibility was tested in a separate cohort of patients with severe mitral regurgitation (n=6). RESULTS: End-diastolic volume (EDV) of both LV and RV decreased during exercise at 55% and 75% HR(max), although a reduction in RVEDV index was only observed at 75% HR(max). Ejection fractions (EF) for both ventricles were significantly higher at 75% HR(max) compared to their respective baselines (LVEF 68%±3% vs. 58%±5%, P=0.001; RVEF 66%±4% vs. 58%±7%, P=0.02). Intra-observer and inter-observer reproducibility of LV parameters was excellent at all 3-stages. Although measurements of RVESV were more variable during exercise, the reproducibility of both RVEF and RV cardiac index was excellent (CV

Purpose Exercise cardiovascular magnetic resonance (Ex-CMR) typically requires complex post-processing or transient exercise cessation, decreasing clinical utility. We aimed to demonstrate the feasibility of assessing biventricular volumes and great vessel flow during continuous in-scanner Ex-CMR, using vendor provided Compressed SENSE (C-SENSE) sequences and commercial analysis software (Cvi42). Methods 12 healthy volunteers (8-male, age: 35 ± 9 years) underwent continuous supine cycle ergometer (Lode-BV) Ex-CMR (1.5T Philips, Ingenia). Free-breathing, respiratory navigated C-SENSE short-axis cines and aortic/pulmonary phase contrast magnetic resonance (PCMR) sequences were validated against clinical sequences at rest and used during low and moderate intensity Ex-CMR. Optimal PCMR C-SENSE acceleration, C-SENSE-3 (CS3) vs C-SENSE-6 (CS6), was further investigated by image quality scoring. Intra-and inter-operator reproducibility of biventricular and flow indices was performed. Results All CS3 PCMR image quality scores were superior (p 0.93). During Ex-CMR, biventricular end-diastolic volumes (EDV) remained unchanged, except right-ventricular EDV decreasing at moderate exercise. Biventricular ejection-fractions increased at each stage. Exercise biventricular cine and PCMR stroke volumes correlated very strongly (r ≥ 0.9), demonstrating internal validity. Intra-observer reproducibility was excellent, co-efficient of variance (COV) Conclusion Biventricular function, aortic and pulmonary flow assessment during continuous Ex-CMR using CS3 sequences is feasible, reproducible and analysable using commercially available software.

Current echocardiographic data reporting the impact of concomitant mitral regurgitation (MR) on outcome in patients who undergo transcatheter aortic valve replacement (TAVR) are conflicting. Using cardiovascular magnetic resonance (CMR) imaging, this study aimed to assess the impact of MR severity on cardiac reverse remodeling and patient outcome. 85 patients undergoing TAVR with CMR pre- and 6 m post-TAVR were evaluated. The CMR protocol included cines for left (LV) and right ventricular (RV) volumes, flow assessment, and myocardial scar assessment by late gadolinium enhancement (LGE). Patients were dichotomised according to CMR severity of MR fraction at baseline (‘non-significant’ vs ‘significant’) and followed up for a median duration of 3 years. Forty-two (49%) patients had ‘significant MR’ at baseline; they had similar LV and RV size and function compared to the ‘non-significant MR’ group but had greater LV mass at baseline. In those with significant MR at baseline, 77% (n = 32) had a reduction in MR post-TAVR, moving them into the ‘non-significant’ category at 6-months, with an overall reduction in MR fraction from 34 to 17% (p

Introduction Delayed breast reconstructions are preferred if post mastectomy radiotherapy is indicated due to lower complication rates compared to immediate permanent implant or autologous reconstructions (AR) but cosmetic outcomes are inferior. Radiotherapy has a deleterious effect on implants and autologous tissue and often an interim tissue expander is place which has inherent pain and complications. However, neoadjuvant radiotherapy (NART) prior to surgery allows for definitive oncological surgery to be performed with an immediate AR in a single operation and the avoidance of a temporary expander. The aim of this study is to assess the safety and downstaging impact of NART. Methods This is a prospective review of patients who underwent NART at GenesisCare Victoria, the Austin and the Alfred hospital. 59 LABC patients (median age 49.2 years) were divided into two groups; clinically staged and pathologically staged for reporting. There were 15 pathologically staged patients (pStage 2A-3C) and 43 clinically staged patients (cStage 2A-3B). All patients initially underwent NACT, followed by NART (median dose 50.4Gy in 28 fractions) to the breast, supraclavicular fossa and level 3 axilla with or without coverage of their Level 1 and 2 axilla, and/or internal mammary nodes. Approximately 6 weeks after completing NART, patients underwent definitive surgery and AR. Results All patients completed their NART with minimal toxicity and no break in treatment. 55 patients had a skin-sparing mastectomy (SSM) and 3 patients had a modified radical mastectomy. All clinically staged patients underwent an AD. ARs with a DIEP flap were performed in the majority of patients (51). The average length of hospitalisation was 6.2 days. The Miller Payne (MP) scoring index was used to record pathological responses in clinically staged patients. Overall 36 patients achieved significant downstaging of their disease, with MP scores of 5/5 for 20 and 4/5 for 16. Only 1 patient failed to achieve any downstaging with a MP score of 1/5. All 12 Her2 positive patients, 3/5 Triple negative patients and 5/26 Luminal A/B patients achieved a MP score of 5/5. All patients achieved R0 resection margins. This included 6 patients who had initial cT4 disease (cT4a X2, cT4b X1 and cT4d X3). 15 patients had initial cN2/3 disease and all successfully underwent their axillary dissections with R0 resections achieved. 10/15 had no involved axillary nodes with significant scarring seen in 6. 5/15 had residual involved nodes with significant scarring seen in 3 patients. Post surgical toxicities were graded using Clavien-Dindo classification. 8 significant grade 3 toxicities were seen in 6 patients, with no grade 4 or 5 toxicities. No patients developed DVT or PE. No flap losses were seen. Median follow up is 23 months. Cosmesis was rated as good to excellent in all cases. 1 patient developed simultaneous loco-regional and distant recurrence with another 3 patients developing distant metastases only. Conclusion This review demonstrated that NART is a safe technique, which has not lead to an increase in surgical complication rates or resulted in a detriment in cosmetic outcome. NART can achieve a shorter, simpler reconstructive journey for patients. Citation Format: Baker C, Chao MW, Jassal S, Neoh D, Bevington E, Hyett A, Grinsell D, Loh SW, Zantuck N, Stoney D, Foley C, Law M, Chew G, Yu V, Cheng M, Guerrieri M, Taylor K, Chipman M, Cokelek M, Lim Joon D, Foroudi F. The safety and pathological impact of neoadjuvant radiotherapy for local advanced breast cancer undergoing mastectomy and autologous reconstruction [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-16.

Patients with rheumatoid arthritis (RA) are at greater risk of major cardiovascular (CV) events, predominantly due to accelerated atherosclerosis, underpinned by inflammation and RA disease factors and also heart failure.1 Overall, modest event rate has necessitated the use of surrogate CV abnormalities of increased CV risk including arterial stiffness. Increased arterial stiffness is well recognised in established RA,2 with early, similar reports using comprehensive and reliable cardiac MRI (CMRI) in our treatment-naive, early onset RA cohort.3 Autopsy, histopathological and clinical studies in general population and RA cohorts with and without CV disease (CVD) suggest citrullinated proteins as a mechanism for atherosclerosis, including presence of citrullination within the atherosclerotic plaque of subjects without RA.4 5 We hypothesised that individuals with circulating anti-cyclic citrullinated peptide (CCP) but no systemic inflammation (of RA typically associated with increased CV risk) also demonstrate …

Background Mitral valve (MV) repair is currently recommended over replacement (1). The guidelines suggesting this are however based on historic evidence which compared outdated techniques of MV replacement. Recent data cast doubts on its validity in the current era of chordal-preservation techniques in MV replacement. Purpose Using cardiovascular magnetic resonance (CMR) imaging, this study aimed to assess the impact of MV repair and MV replacement on cardiac left ventricular (LV) reverse remodelling. Methods 65 patients with moderate-severe and severe mitral regurgitation (MR) were prospectively recruited. Of these, 37 patients (59% men, 65±15 years) to date with paired CMR scans at baseline and at 6 months were evaluated. Patients either underwent MV repair (n=9), MV replacement (n=10) or watchful waiting (n=18). The CMR protocol included cines for left ventricle (LV), left atria (LA), and aortic flow assessment. The LA and LV parameters, and MR fraction were analysed. Results At 6 months, both the MV repair and replacement groups exhibited a reduction in LV end-diastolic volume (LVEDV) and LA volumes when compared to the control group. The indexed LVEDV decreased significantly from 129±33ml/m2 to 99±37ml/m2, p Conclusion MV surgery leads to atrial and left ventricular reverse remodelling, and a decline in global LV ejection fraction. In this small series, MV replacement with chordal preservation showed similar cardiac reverse remodelling benefits to MV repair. Although residual MR is often seen following repair, this did not lead to less favourable cardiac reverse remodelling. Acknowledgement/Funding Leeds NIHR infrastructure

Background: Athletic cardiac remodeling can occasionally be difficult to differentiate from pathological hypertrophy. Detraining is a commonly used diagnostic test to identify physiological hypertrophy, which can be diagnosed if hypertrophy regresses. We aimed to establish whether athletic cardiac remodeling assessed by cardiovascular magnetic resonance is mediated by changes in intracellular or extracellular compartments and whether this occurs by 1 or 3 months of detraining. Methods: Twenty-eight athletes about to embark on a period of forced detraining due to incidental limb bone fracture underwent clinical assessment, ECG, and contrast-enhanced cardiovascular magnetic resonance within a week of their injury and then 1 month and 3 months later. Results: After 1 month of detraining, there was reduction in left ventricular (LV) mass (130±28 to 121±25 g; P P =0.02), and extracellular volume fraction (24.5±2.3% to 26.0±2.6%; P =0.0007) with no further changes by 3 months. The decrease in LV mass was mediated by a decrease in intracellular compartment volume (94±22 to 85±19 mL; P Conclusions: Regression of athletic LV hypertrophy can be detected after just 1 month of complete detraining and is mediated by a decrease in the intracellular myocardial compartment with no change in the extracellular compartment. Further studies are needed in athletes with overt and pathological hypertrophy to establish whether native T1 and extracellular volume fraction may complement electrocardiography, echocardiography, cardiopulmonary exercise testing, and genetic testing in predicting the outcome of detraining.

Supplemental Digital Content is available in the text., Background: Long-term right ventricular (RV) pacing leads to heart failure or a decline in left ventricular (LV) function in up to a fifth of patients. We aimed to establish whether patients with focal fibrosis detected on late gadolinium enhancement cardiovascular magnetic resonance (CMR) have deterioration in LV function after RV pacing. Methods: We recruited 84 patients with LV ejection fraction ≥40% into 2 observational CMR studies. Patients (n=34) with a dual-chamber device and preserved atrioventricular conduction underwent CMR in 2 asynchronous pacing modes (atrial asynchronous and dual-chamber asynchronous) to compare intrinsic atrioventricular conduction with forced RV pacing. Patients (n=50) with high-grade atrioventricular block underwent CMR before and 6 months after pacemaker implantation to investigate the medium-term effects of RV pacing. Results: The key findings were (1) initiation of RV pacing in patients with fibrosis, compared with those without, was associated with greater immediate changes in both LV end-systolic volume index (5.3±3.5 versus 2.1±2.4 mL/m2; P1.1 g of fibrosis with 90% sensitivity and 70% specificity. Conclusions: Fibrosis detected on CMR is associated with immediate- and medium-term deterioration in LV function following RV pacing and could be used to identify those at risk of heart failure before pacemaker implantation.

Background Non-invasive assessment of myocardial ischaemia is a cornerstone of the diagnosis of coronary artery disease. Measurement of myocardial blood flow (MBF) using positron emission tomography (PET) is the current reference standard for non-invasive quantification of myocardial ischaemia. Dynamic myocardial perfusion cardiovascular magnetic resonance (CMR) offers an alternative to PET and a recently developed method with automated inline perfusion mapping has shown good correlation of MBF values between CMR and PET. This study assessed the repeatability of myocardial perfusion mapping by CMR in healthy subjects. Methods Forty-two healthy subjects were recruited and underwent adenosine stress and rest perfusion CMR on two visits. Scans were repeated with a minimum interval of 7 days. Intrastudy rest and stress MBF repeatability were assessed with a 15-min interval between acquisitions. Interstudy rest and stress MBF and myocardial perfusion reserve (MPR) were measured for global myocardium and regionally for coronary territories and slices. Results There was no significant difference in intrastudy repeated global rest MBF (0.65 ± 0.13 ml/g/min vs 0.62 ± 0.12 ml/g/min, p = 0.24, repeatability coefficient (RC) =24%) or stress (2.89 ± 0.56 ml/g/min vs 2.83 ± 0.64 ml/g/min, p = 0.41, RC = 29%) MBF. No significant difference was seen in interstudy repeatability for global rest MBF (0.64 ± 0.13 ml/g/min vs 0.64 ± 0.15 ml/g/min, p = 0.80, RC = 32%), stress MBF (2.71 ± 0.61 ml/g/min vs 2.55 ± 0.57 ml/g/min, p = 0.12, RC = 33%) or MPR (4.24 ± 0.69 vs 3.73 ± 0.76, p = 0.25, RC = 36%). Regional repeatability was good for stress (RC = 30–37%) and rest MBF (RC = 32–36%) but poorer for MPR (RC = 35–43%). Within subject coefficient of variation was 8% for rest and 11% for stress within the same study, and 11% for rest and 12% for stress between studies. Conclusions Fully automated, inline, myocardial perfusion mapping by CMR shows good repeatability that is similar to the published PET literature. Both rest and stress MBF show better repeatability than MPR, particularly in regional analysis. Electronic supplementary material The online version of this article (10.1186/s12968-018-0462-y) contains supplementary material, which is available to authorized users.

Background Left ventricular systolic dysfunction (LVSD) is associated with reduced myocardial perfusion reserve (MPR) even in the absence of proven ischaemic heart disease and patients may have typical angina symptoms, despite the lack of obstructive coronary artery disease. The severity of MPR reduction has been suggested as a prognostic marker in both ischaemic and non-ischaemic cardiomyopathy. We hypothesised that reduction in MPR was associated with worsening symptomatology (NYHA class) and systolic dysfunction (ejection fraction, EF). Methods 40 patients referred from cardiology clinics with LVSD of unknown cause underwent adenosine stress perfusion CMR (Siemens 3T). First pass stress and rest myocardial perfusion CMR data were acquired in three short axis slices with 0.05 mmol/kg intravenous Gadovist using a recently reported free-breathing motion corrected Method with in-line quantification of perfusion maps. For stress, adenosine was administered at 140 mcg/kg/min over 5 min. Segments showing regional perfusion defects or containing scar were excluded from further quantitative analysis. Myocardial blood flow (MBF) was calculated globally for the remaining left ventricle. Patients with no evidence of LVSD (EF-55%) were excluded from analysis. NYHA class was recorded at the time of CMR scan. EF was calculated from a short axis cine data set and classified as: mild (45%), moderate (35­44%) and severe (34%) impairment. ANOVA with post hoc Bonferroni correction was used to compare means of the three groups. Results Patients were grouped both by NYHA class and by EF severity, comparisons of these groups are shown in Table 1. No significant difference was seen between groups with respect to age, resting heart rate and resting MBF. MPR was associated with NYHA class (figure 1). A greater reduction in MPR was associated with a higher NYHA class and there was a significant decrease in MPR between asymptomatic patients and those with exercise limitation (Mean MPR 2.90±0.96, 2.05±0.61, 1.45±0.45 for classes I, II and III respectively, p No significant difference was seen between NYHA II and III (2.05 vs 1.45, p=0.32) although a trend to decreasing MPR was observed. Myocardial perfusion reserve did not correlate with severity of LV dysfunction (figure 2). Conclusion A reduction in MPR is associated with NYHA class in systolic heart failure, independent of ejection fraction. These findings suggest potential therapeutic targets for symptomatic improvement, including use of vasodilators, even in the absence of coronary disease.

Background CMR image acquisition techniques during exercise typically require transient cessation of exercise or complex post-processing analysis, potentially compromising its clinical utility. We evaluated the feasibility and reproducibility of a novel image acquisition Method for the assessment of biventricular physiological response during continuous physical exercise. Methods 10 healthy volunteers (80% men, age 25±2 years) underwent supine cycle ergometer (Lode) induced exercise CMR (Philips 1.5T Ingenia) on two separate occasions using a free-breathing, multi-shot, navigated, balanced steady-state free precession cine pulse sequence. Individual target heart rates (HR) for both moderate and high-intensity exercise were prescribed based on a prior supine cardiopulmonary exercise test (CPET). The scan protocol included a short axis ventricular volume stack and a 40 phase 4-chamber cine. Images were acquired at baseline, and during steady-state moderate and high-intensity exercise (55% and 75% maximal heart rate, respectively). Data were analysed by two independent observers and left and right ventricular (LV, RV) indices calculated. Results End-diastolic volume (EDV) of both LV and RV decreased during moderate and high-intensity exercise, although the reduction in indexed RVEDV (RVEDVi) was only observed during maximal exercise (table 1). Similarly, a significant reduction in end-systolic volumes (ESV) was seen in both ventricles, whilst the reduction in indexed LVESV (LVESVi) was only evident during high-intensity exercise. Ejection fraction (EF) increased from rest to moderate and high intensity exercise in the LV (LVEF 58±5% vs 61±8% vs 68±3%, respectively; p Intra-observer reproducibility of LV parameters was excellent at all three stages (Table 2), although measurements of RVESV were more variable. The reproducibility of both RVEF and RV cardiac indexes was however excellent. Similarly, inter-observer reproducibility of LV volumes, EF and cardiac indexes was excellent. Inter-scan LV and RV ejection fraction were highly reproducible at all 3 stages; RVESVi reproducibility was suboptimal. Conclusion This exercise CMR protocol using a novel free-breathing, multi-shot, navigated imaging Method allows simultaneous assessment of the left and right ventricular response to continuous exercise. Intra and inter-observer reproducibility were excellent. Clinical feasibility and utility now needs to be established.

The natural history of mitral regurgitation (MR) results in significant morbidity and mortality. Innovations in non-invasive imaging have provided new insights into the pathophysiology and quantification of MR, in addition to early detection of left ventricular (LV) dysfunction and prognostic assessment in asymptomatic patients. Transthoracic (TTE) and transesophageal (TOE) echocardiography are the mainstay for diagnosis, assessment and serial surveillance. However, the advance from 2D to 3D imaging leads to improved assessment and characterization of mitral valve (MV) disease. Cardiovascular magnetic resonance (CMR) is increasingly used for MR quantitation and can provide an alternative imaging method if echocardiography is suboptimal or inconclusive. Other techniques such as exercise echocardiography, tissue Doppler imaging and speckle-tracking echocardiography can further offer complementary information on prognosis. This review summarises the current evidence for state-of-the-art cardiovascular imaging for the investigation of MR. Whilst advanced echocardiographic techniques are superior in the evaluation of complex MV anatomy, CMR appears the most accurate technique for the quantification of MR severity. Integration of multimodality imaging for the assessment of MR utilises the advantages of each imaging technique and offers the most comprehensive assessment of MR.

Introduction Myocardial infraction (MI) leads to complex changes in left ventricular (LV) haemodynamics. It remains unknown how four-dimensional (4D) acute changes in LV-cavity blood flow kinetic energy (KE) affect LV remodelling. We hypothesised that LV blood flow energetics is independently associated with adverse LV-remodelling. Methods We recruited 69 revascularised ST-elevation MI patients. All patients underwent cardiovascular magnetic resonance (CMR) at 1.5 T within 48 hours and at 3 months. CMR included cines, early/late gadolinium enhancement and whole-heart 4D flow. CMR analysis included: LV volumes, infarct size (IS,%), microvascular obstruction (MVO,%), two-dimensional, retrospective valve tracking derived mitral inflow metrics and 4D KE components. KE was derived using novel, semi-automated method by using endocardial contours on short-axis cines to extract intra-cavity velocity profile. Adverse LV-remodelling was defined as increase in LV end-diastolic volume by 15%. Results Thirteen (19%) patients developed adverse LV-remodelling. Demographics were comparable between patients with/without remodelling. Baseline CMR in adverse LV-remodelling-group showed significantly lower EF, LV KE, Systolic, A-wave, in-plane KEs and increased MVO (p Conclusion LV haemodynamic assessment by novel, semi-automated, 4D KE mapping adds incremental value to predict adverse LV-remodelling. A-wave KE and MVO size early after acute MI are independently associated with adverse LV-remodelling.

Introduction Athletes who train regularly can develop left ventricular (LV) hypertrophy, which can be difficult to differentiate from hypertrophic cardiomyopathy. We aimed to use cardiovascular magnetic resonance (CMR) tissue characterisation to assess the cardiac effects of complete detraining. Methods Athletes (n=26) with a limb fracture that prohibited training for >1 month had identical CMR protocol including volumetric analysis and T1 mapping on Philips Acheiva 3.0 T Results Athletes exercised for 7.7±2.3 hours per week and were predominantly male (21/26). LV mass at baseline was 131±27 g, decreasing to 120±23 g after one month detraining (p=0.003). It did not decrease further by three months 122±21 g (p=NS). Reduction in LV mass after one month was mediated by regression of the cardiac myocyte compartment (100±22 g to 90±18 g, p 10% decrease in LV mass (n=9) after one month detraining (AUC 0.90, 95% CI: 0.71 to 0.98, p 54 g/m2 (67% sensitivity, 94% specificity). Conclusion Regression of LV hypertrophy occurs within one month of complete detraining and is mediated by regression of cardiac myocyte mass rather than extracellular compartment. In the athlete with unexplained LV hypertrophy increased myocyte mass has the potential to diagnose physiological remodelling without the need for detraining.

Background Myocardial infarction (MI) leads to complex changes in left ventricular (LV) haemodynamics that are linked to clinical outcomes. We hypothesize that LV blood flow kinetic energy (KE) is altered in MI and is associated with LV function and infarct characteristics. This study aimed to investigate the intra-cavity LV blood flow KE in controls and MI patients, using cardiovascular magnetic resonance (CMR) four-dimensional (4D) flow assessment. Methods Forty-eight patients with MI (acute-22; chronic-26) and 20 age/gender-matched healthy controls underwent CMR which included cines and whole-heart 4D flow. Patients also received late gadolinium enhancement imaging for infarct assessment. LV blood flow KE parameters were indexed to LV end-diastolic volume and include: averaged LV, minimal, systolic, diastolic, peak E-wave and peak A-wave KEiEDV. In addition, we investigated the in-plane proportion of LV KE (%) and the time difference (TD) to peak E-wave KE propagation from base to mid-ventricle was computed. Association of LV blood flow KE parameters to LV function and infarct size were investigated in all groups. Results LV KEiEDV was higher in controls than in MI patients (8.5 ± 3 μJ/ml versus 6.5 ± 3 μJ/ml, P = 0.02). Additionally, systolic, minimal and diastolic peak E-wave KEiEDV were lower in MI (P

Aims: Cardiac hypertrophy develops from prolonged, severe iron deficiency (ID), but little is known about its function. We hypothesized that 4 weeks of ID would result in enhanced cardiac function, but would transition to loss by 9 weeks. Study Design: 38 rats were fed either control or ID diets for 4, 6, or 9 weeks, then subjected to a pressure-volume loop protocol to assess cardiac function. Place and Duration of Study: Biology Department, Western Wyoming College, between January 2013 and December 2013. Methodology: Rats were anesthetized with ketamine/xylazine, catheters placed in femoral and jugular veins. A pressure-conductance microcatheter was inserted through the right carotid artery, to the left ventricle. Baseline data was collected for 10 minutes, followed by occlusion of the inferior vena cava to reduce venous return. Hypertonic saline was infused through the jugular vein to allow for parallel conductance subtraction. Rats were sacrificed, and hearts and blood collected for mass and volume calibration, respectively. Original Research Article Chew Jr et al.; BJMMR, 5(4): 434-443, 2015; Article no.BJMMR.2015.048 435 Results: Cardiac output was increased (P = .01) with ID after 4 weeks, but was not increased after 6 or 9 weeks. The increase was due to enhanced stroke volume (P = .02), but not heart rate (P = .48). Stroke volume was increased due to enhanced contractility with ID (P = .03), along with a decrease in the pressure at which ejection begins (afterload, P = .001). By 9 weeks, contractility was decreased (P = .01), but afterload remained lower. Cardiac efficiency was enhanced after 4 weeks (P = .002), which was lost by 9 weeks of ID. No diastolic parameters of cardiac function were altered by ID. Conclusion: An adaptive compensation of cardiac function develops within 4 weeks of severe ID, but is lost within weeks, at which time, the ID heart is in a state of pathological decompensation.

Objectives: We sought to determine the relationship between changes in natriuretic peptides and symptoms as a consequence of introducing beta-blocker therapy, in patients with chronic heart failure (CHF) and persistent atrial fibrillation (AF). Methods: In a randomised, double-blind, placebo-controlled study involving 47 patients with CHF and persistent AF (mean age 68 years and 62% men), we analysed the individual change (Δ) in B-type natriuretic peptide (BNP) level to the introduction of carvedilol (titrated to a target dose of 25 mg twice daily, group A) or placebo (group B) in addition to background treatment with digoxin. Symptoms score, 6-min walk distance, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), heart rate (24-hour ECG) and BNP were measured at baseline and at 4 months. Results: LVEF (Δ median +5 vs. +0.4, p = 0.048), symptoms score (Δ median -4 vs. 0, p = 0.04), NYHA class (Δ median -33% vs. +3% in NYHA class 3-4, p = 0.046) and heart rate [Δ median 24-hour ventricular rate (VR) -19 vs. -2, p < 0.0001] improved with combination therapy of digoxin and carvedilol compared to digoxin alone, but BNP (Δ median +28 vs. -6 , p = 0.11) trended in the opposite direction. There was no relationship between the degree of symptomatic improvement or VR control and BNP response. Conclusion: After the introduction of carvedilol, clinical outcome appears unrelated to BNP changes in patients with CHF and AF. Changes in BNP cannot be used as a marker of clinical response in terms of symptoms or cardiac function in this setting.

Thyroid storm is a hypermetabolic state due to acute elevation of thyroid hormones precipitated by multiple causes. It’s a rare life threatening emergency, and failure of prompt aggressive treatment will lead to multiorgan dysfunction and complicate further treatment plans. In this report we described our experience of managing a severe thyroid storm patient with contraindication to carbimazole, the complexities encountered with conventional treatment methods and alternative aggressive remedy options.

Background Expansion of the myocardial extracellular volume (ECV) is a surrogate measure of focal/diffuse fibrosis and is an independent marker of prognosis in chronic heart disease. Changes in ECV may also occur after myocardial infarction, acutely because of oedema and in convalescence as part of ventricular remodelling. The objective of this study was to investigate changes in the pattern of distribution of regional (normal, infarcted and oedematous segments) and global left ventricular (LV) ECV using semi-automated methods early and late after reperfused ST-elevation myocardial infarction (STEMI). Methods Fifty patients underwent cardiovascular magnetic resonance (CMR) imaging acutely (24 h–72 h) and at convalescence (3 months). The CMR protocol included: cines, T2-weighted (T2 W) imaging, pre−/post-contrast T1-maps and LGE-imaging. Using T2 W and LGE imaging on acute scans, 16-segments of the LV were categorised as normal, oedema and infarct. 800 segments (16 per-patient) were analysed for changes in ECV and wall thickening (WT). Results From the acute studies, 325 (40.6%) segments were classified as normal, 246 (30.8%) segments as oedema and 229 (28.6%) segments as infarct. Segmental change in ECV between acute and follow-up studies (Δ ECV) was significantly different for normal, oedema and infarct segments (0.8 ± 6.5%, −1.78 ± 9%, −2.9 ± 10.9%, respectively; P

Iron deficiency is associated with multiple health problems, including the cardiovascular system. However, the mechanism of action of iron-deficiency-induced cardiovascular damage is unclear. The aim of the present study was to examine the effect of dietary iron deficiency on cardiac ultrastructure, mitochondrial cytochrome c release, NOS (nitric oxide synthase) and several stress-related protein molecules, including protein nitrotyrosine, the p47phox subunit of NADPH oxidase, caveolin-1 and RhoA. Male weanling rats were fed with either control or iron-deficient diets for 12 weeks. Cardiac ultrastructure was examined by transmission electron microscopy. Western blot analysis was used to evaluate cytochrome c, endothelial and inducible NOS, NADPH oxidase, caveolin-1 and RhoA. Protein nitrotyrosine formation was measured by ELISA. Rats fed an iron-deficient diet exhibited increased heart weight and size compared with the control group. Heart width, length and ventricular free wall thickness were similar between the two groups. However, the left ventricular dimension and chamber volume were significantly enhanced in the iron-deficient group compared with controls. Ultrastructural examination revealed mitochondrial swelling and abnormal sarcomere structure in iron-deficient ventricular tissues. Cytochrome c release was significantly enhanced in iron-deficient rats. Protein expression of eNOS (endothelial NOS) and iNOS (inducible NOS), and protein nitrotyrosine formation were significantly elevated in cardiac tissue or mitochondrial extraction from the iron-deficient group. Significantly up-regulated NADPH oxidase, caveolin-1 and RhoA expression were also detected in ventricular tissue of the iron-deficient group. Taken together, these results suggest that dietary iron deficiency may have induced cardiac hypertrophy characterized by aberrant mitochondrial and irregular sarcomere organization, which was accompanied by increased reactive nitrogen species and RhoA expression.

Background NICE 2010 guidelines (CG95) proposed investigation according to pre-test likelihood (PTL) of coronary artery disease (CAD) in patients presenting with stable chest pain; low risk patients are referred for CT coronary angiography (CTCA), intermediate risk should have a functional test (stress echocardiography, MPS, CMR) with invasive angiography reserved for high risk patients and those with a PTL>90% having no investigation and treated prospectively as angina. The 2016 update to CG95 now recommends referral for CTCA in all patients with typical or atypical chest pain and in those with non-anginal pain but with ECG changes, with functional imaging reserved for those who have previously documented coronary disease or revascularisation. Our aim was to compare imaging resource utilisation between the 2010 and 2016 guideline recommendations to highlight the potential service implications if followed explicitly. Methods Consecutive patients referred over 4 weeks to the Leeds General Infirmary rapid access chest pain clinic (RACPC) with stable chest pain symptoms were prospectively evaluated. Non identifiable data was collected on demographics, typicality of chest pain symptoms and ECG findings and subsequently requested 1st line investigation. Patient notes were reviewed and PTL for patients was calculated in accordance with CG95 and hypothetical investigative strategies calculated according to both 2010 and 2016 guidelines. Results 157 consecutive patients were evaluated between 17th October and 17th November 2016. Patient demographics are displayed in table 1. 37 (23.5%) patients had typical angina, 55 (35.0%) had atypical angina, 65 (41.4%) had non-anginal symptoms. 16 (10.2%) patients had previous infarction/revascularisation. 25 (15.9%) patients had a PTL 90%. Table 2 shows diagnostic tests requested and hypothetical investigative strategies according to NICE 2010 CG95 and the 2016 update. Conclusion/Implications Our results show that if implemented in proposed 2016 form there will be a significant increase in the referral rate for CTCA with a corresponding decrease in referral for functional imaging and angiography. Furthermore the number of patients that are not investigated would more than double following the introduction of the proposed NICE 2016 guidelines. CTCA has high sensitivity for the diagnosis of CAD but more limited specificity and concerns are that increased usage in intermediate/high risk patients may lead to increased rates of unnecessary angiography due to the overestimation of severity of CAD. The change in guidelines would lead to a significant shift in practice that has implications for both workforce planning and provision of resources.

A 43-year-old man with liver failure caused by alcohol abuse and congenital hepatic fibrosis was examined for intermittent fever of unknown origin. He had portal hypertension, which was complicated in the past by bleeding varices that required a portocaval shunt. There were no localizing symptoms or signs for the fever, and, apart from an elevated leukocyte count, results of investigations including urine and blood cultures, abdominal ultrasound, abdominal magnetic resonance imaging, and endoscopic retrograde cholangiopancreatography were not helpful. A labeled leukocyte scan was obtained with Tc-99m stannous colloid. The 1-, 3-, and 24-hour images showed marked reduction in tracer uptake within the liver, with increased tracer accumulation in an enlarged spleen and marrow. Marked margination of labeled leukocytes in the lungs was also evident, which subsided on the 24-hour image. The focus of inflammation was not identified, and instead the tracer distribution pattem was similar to that on a Tc-99m sulfur colloid scan in a patient with liver failure. The scan appearances presumably represent reduced uptake of free Tc-99m stannous colloid by Kuppfer cells of the failing liver, with a shift in uptake to the reticuloendothelial system of the spleen and marrow.

The improved survival following the diagnosis of breast cancer has potentially altered the characteristics and course of patients presenting with CNS involvement. We therefore sought to define our current cohort of breast cancer patients with metastatic disease to the CNS in regard to modern biomarkers and clinical outcome. Review of clinical and radiographic records of women presenting to a tertiary medical center with the new diagnosis of CNS metastatic disease from breast cancer. This was a retrospective review from patients identities obtained from two prospective databases. There were 88 women analyzed who were treated over the period of January 2003 to February 2010, average age 56.9 years. At the time of initial presentation of CNS disease, 68 % of patients had multiple brain metastases, 17 % had a solitary metastasis, and 15 % had only leptomeningeal disease (LMD). The median survival for all patients from the time of diagnosis of breast disease was 50.0 months, and 9.7 months from diagnosis of CNS involvement. The only factor related to overall survival was estrogen receptor-positive pathology (57.6 v. 38.2 months, p = .02 log-rank); those related to survival post CNS diagnosis were presentation with LMD (p = .004, HR = 3.1, Cox regression) and triple-negative hormonal/HER2 status (p = .02, HR = 2.3, Cox regression). Patients with either had a median survival of 3.1 months (no patients in common). Of the 75 patients who initially presented with metastatic brain lesions, 20 (26 %) subsequently developed LMD in the course of their disease (median 10.4 months), following which survival was grim (1.8 months median). Symptoms of LMD were most commonly lower extremity weakness (14/33), followed by cranial nerve deficits (11/33). The recently described Graded Prognostic Assessment (GPA) tumor index stratified median survival at 2.5, 5.9, 13.1, and 21.7 months, respectively, for indices of 1–4 (p = .004, log-rank), which contrasted with the nonsignificant survival difference between Radiation Therapy Oncology Group Recursive Partitioning Analysis classes one and two. (13.1 v. 13.2, p = .8, log-rank). Treatment of patients with metastatic brain disease from breast cancer should be tailored to the patient’s hormonal status and GPA index. Practitioners must be vigilant for the development of LMD, especially as it often presents with nondescript complaints such as back pain.

Methamphetamine, a commonly seen substance of abuse, has been reported to exert detrimental effect on bodily function including the cardiovascular system although its mechanism of action is poorly understood. This study was designed to examine the direct impact of methamphetamine on isolated whole heart and single cardiomyocyte contractile function. Murine hearts and isolated cardiomyocytes from adult FVB mice were exposed to various concentrations of methamphetamine for 30min prior to the assessment of mechanical function using a Langendroff apparatus and an IonOptix Myocam system, respectively. Cardiac contractile properties analyzed included maximal velocity of left ventricular pressure development and decline (+/-dP/dt), peak shortening amplitude (PS), maximal velocity of shortening/relengthening (+/-dLdt), time-to-PS (TPS), time-to-90% relengthening (TR(90)), resting and electrically stimulated increase of intracellular Ca(2+) as well as intracellular Ca(2+) decay. Our results revealed that acute methamphetamine exposure depressed +/-dP/dt, PS and rise of intracellular Ca(2+) without affecting +/-dLdt, TPS, TR(90), resting intracellular Ca(2+) and intracellular Ca(2+) decay. Furthermore, methamphetamine nullified the adrenergic agonist norepinephrine-elicited positive cardiomyocyte contractile response, including elevated PS, +/-dLdt and shortened TR(90) without affecting TPS. Western blot analysis showed unchanged expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a) and phospholamban, associated with upregulated Na(+)-Ca(2+) exchanger levels following acute methamphetamine exposure. In addition, methamphetamine promoted overt cardiomyocyte protein damage evaluated by carbonyl formation. Taken together, these results demonstrate direct cardiac depressant effect of methamphetamine in myocardium and isolated cardiomyocytes, possibly associated with protein damage and dampened adrenergic response.

Cervical (C)-spine clearance protocols exist both to identify traumatic injury and to expedite rigid collar removal. Computed tomography (CT) of the C-spine in trauma patients facilitates the removal of immobilization collars in patients who are neurologically intact, and magnetic resonance imaging (MRI) has become an indispensable adjunct for evaluating trauma patients with neurologic deficits. Yet, the management of patients with impaired mental status who lack neurologic deficits attributable to the spinal cord remains controversial. C-spine MRI has been suggested and employed as an imaging modality to exclude occult C-spine instability in this population of patients. However, currently available data are inconclusive as to the necessity of MRI in the C-spine clearance of obtunded or comatose trauma patients with a normal CT.The records of patients undergoing contemporaneous CT and MRI of the C-spine in a level I trauma center from January 2003 to December 2006 were retrospectively analyzed. From this group, patients admitted with a Glasgow Coma Scale score/=13 and a normal C-spine CT with sagittal and coronal reconstructions were identified. Patients were excluded if a neurologic deficit potentially referable to the spinal cord was identified. The results of C-spine MRI in this group were tabulated and analyzed.A total of 690 patients were identified who had undergone contemporaneous C-spine CT and MRI. Of this group, 180 patients (26.2%) were identified as having a normal CT with sagittal and coronal reconstructions, no neurologic deficit, and Glasgow Coma Scale score/=13. Within this group, the average time interval between CT and MRI was 4.6 days (median, 4 days). Among these 180 patients, C-spine MRI identified 38 patients (21.1%) with acute traumatic findings in the cervical spine. However, none of these patients had a missed unstable injury and no patient required surgery or developed evidence of delayed instability.Our data suggests that, outside of its appropriate application to patients with a neurologic deficit, MRI is unlikely to uncover unstable C-spine injuries in patients who are obtunded or comatose when C-spine CT using modern imaging protocols is normal.

A 22-year-old woman who was 17 weeks postpartum and breast feeding her infant was examined for possible Graves' disease. Her thyroid scan showed a diffuse goiter, with a low normal tracer uptake (0.64%; normal range, 0.5% to 2.5%), with competition from marked breast tracer uptake (19%). Marked lactating breast avidity has been documented for various radiopharmaceuticals, with marked interindividual variability in the degree of tracer expression in the milk. Despite the prominent breast uptake, at 2 hours postinjection the calculated activity in the milk expressed equated to an extraction fraction of 3.98 E-4 per milliliter which is within the literature quoted limits (7).

We hypothesized that the structure of systemic arteries would be altered following 10-14 wk of hindlimb unloading (tail suspension) in female Sprague-Dawley rats. Tail suspension resulted in atrophy of the soleus muscle (P < or = 0.01) but no significant differences in the mass of the extensor digitorum muscle, heart, or adrenal glands. In anesthetized rats, there was no difference between groups in arterial pressure (approximately 60 mm Hg). The corresponding maximal (topical papaverine) external diameter (ED) of femoral arteries (N = 5 per group) was reduced (P < or = 0.05) in tail suspended (TS, 511 +/- 47 microm, mean +/- SD) compared with cage sedentary (CS, 615 +/- 89 microm) and food restricted weight-paired (FR, 643 +/- 61 microm) groups. Neither hematocrit, red cell, plasma, nor total blood volume differed among groups. Following systemic vasodilation with papaverine, progressive arterial inflation with liquid silicon rubber (Microfil) revealed a reduction in both ED and distensibility of the femoral artery (P < or = 0.05). To determine the effects of tail suspension on systemic arterial morphology, the vasculature of additional rats was perfusion fixed at 80 mm Hg during vasodilation. Cross sections (thickness, 8 microm) of the carotid, axillary, iliac, and femoral arteries were then evaluated. Whereas the internal diameter of femoral arteries was smaller in TS than in CS (P < 0.05), no differences were observed for other vessels among groups. Further, arterial wall thickness increased systemically (overall, P < 0.05; carotid, 24%, P < 0.01; femoral, 28%, P < 0.01) following tail suspension. These findings illustrate adaptation in the structure of conduit arteries to prolonged tail suspension, with diameter altered regionally and wall thickness increased systemically. We suggest that chronic changes in activity patterns can influence arterial structure.

4588 Background: AGS-003 is an autologous immunotherapy prepared from matured monocyte-derived dendritic cells co-electroporated with the subject's own amplified tumor and synthetic CD40L RNA. Base...