Assessment of stable coronary artery disease by cardiovascular magnetic resonance imaging: Current and emerging techniques

Coronary artery disease (CAD) is a leading cause of death and disability worldwide. Cardiovascular magnetic resonance (CMR) is established in clinical practice guidelines with a growing evidence base supporting its use to aid the diagnosis and management of patients with suspected or established CAD. CMR is a multi-parametric imaging modality that yields high spatial resolution images that can be acquired in any plane for the assessment of global and regional cardiac function, myocardial perfusion and viability, tissue characterisation and coronary artery anatomy, all within a single study protocol and without exposure to ionising radiation. Advances in technology and acquisition techniques continue to progress the utility of CMR across a wide spectrum of cardiovascular disease, and the publication of large scale clinical trials continues to strengthen the role of CMR in daily cardiology practice. This article aims to review current practice and explore the future directions of multi-parametric CMR imaging in the investigation of stable CAD

A comparison of cardiovascular magnetic resonance and single photon emission computed tomography (SPECT) perfusion imaging in left main stem or equivalent coronary artery disease: a CE-MARC substudy

Background: Assessment of left main stem (LMS) stenosis has prognostic and therapeutic implications. Data on assessment of LMS disease by cardiovascular magnetic resonance (CMR) and single photon emission computed tomography (SPECT) are limited. CE-MARC is the largest prospective comparison of CMR and SPECT against quantitative invasive coronary angiography (QCA) for detection of coronary artery disease (CAD), and provided the framework for this evaluation. The aims of this study were to compare diagnostic accuracy of visual and quantitative perfusion CMR to SPECT in patients with LMS stable CAD. Methods: Fifty-four patients from the CE-MARC study were included: 27 (4%) with significant LMS or LMS-equivalent disease on QCA, and 27 age/sex-matched patients with no flow-limiting CAD. All patients underwent multi-parametric CMR, SPECT and QCA. Performance of visual and quantitative perfusion CMR by Fermi-constrained deconvolution to detect LMS disease was compared with SPECT. Results: Of 27 patients in the LMS group, 22 (81%) had abnormal CMR and 16 (59%) had abnormal SPECT. All patients with abnormal CMR had abnormal perfusion by visual analysis. CMR demonstrated significantly higher area under the curve (AUC) for detection of disease (0.95; 0.85–0.99) over SPECT (0.63; 0.49–0.76) (p = 0.0001). Global mean stress myocardial blood flow (MBF) by CMR in LMS patients was significantly lower than controls (1.77 ± 0.72 ml/g/min vs. 3.28 ± 1.20 ml/g/min, p < 0.001). MBF of <2.08 ml/g/min had sensitivity of 78% and specificity of 85% for diagnosis of LMS disease, with an AUC (0.87; 0.75–0.94) not significantly different to visual CMR analysis (p = 0.18), and more accurate than SPECT (p = 0.003). Conclusion: Visual stress perfusion CMR had higher diagnostic accuracy than SPECT to detect LMS disease. Quantitative perfusion CMR had similar performance to visual CMR perfusion analysis

Micro-CT Imaging Reveals Mekk3 Heterozygosity Prevents Cerebral Cavernous Malformations in Ccm2-Deficient Mice.

Mutations in CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral cavernous malformation in humans. Mouse models of CCM disease have been established by deleting Ccm genes in postnatal animals. These mouse models provide invaluable tools to investigate molecular mechanism and therapeutic approaches for CCM disease. However, the full value of these animal models is limited by the lack of an accurate and quantitative method to assess lesion burden and progression. In the present study we have established a refined and detailed contrast enhanced X-ray micro-CT method to measure CCM lesion burden in mouse brains. As this study utilized a voxel dimension of 9.5μm (leading to a minimum feature size of approximately 25μm), it is therefore sufficient to measure CCM lesion volume and number globally and accurately, and provide high-resolution 3-D mapping of CCM lesions in mouse brains. Using this method, we found loss of Ccm1 or Ccm2 in neonatal endothelium confers CCM lesions in the mouse hindbrain with similar total volume and number. This quantitative approach also demonstrated a rescue of CCM lesions with simultaneous deletion of one allele of Mekk3. This method would enhance the value of the established mouse models to study the molecular basis and potential therapies for CCM and other cerebrovascular diseases

Identifying the attributes of a profession in the practice and regulation of fire safety engineering

Fire Safety Engineering is often implemented within a framework that requires a recognized and recognizable profession. This article reviews the current state of various attributes that define Fire Safety Engineering as a profession. It is argued that: 1) reliance on prescriptive solutions opens the domain to practitioners that do not possess the required specialist knowledge; 2) the fire safety engineering process is often triggered through non-compliances to individual prescriptive provisions, negatively impacting on the discipline's professional authority; 3) the discipline operates in a manner that exposes it to challenges of its ethical code; and 4), the lack of a well-defined accreditation framework challenges the professional culture. The resulting environment favours a customer relationship between those commissioning the work and the Fire Safety Engineer, rather than the client relationship necessary for professional practise. Most engineering disciplines respond to failures by formalisation of the profession around its duty of care to society. Conversely, in Fire Safety Engineering such responses have focused on regulation. Recent incidents are a significant impetus and opportunity for the fire safety profession to better formalize itself

Ventricular longitudinal function is associated with microvascular obstruction and intramyocardial haemorrhage.

Microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) are associated with adverse prognosis, independently of infarct size after reperfused ST-elevation myocardial infarction (STEMI). Mitral annular plane systolic excursion (MAPSE) is a well-established parameter of longitudinal function on echocardiography.We aimed to investigate how acute MAPSE, assessed by a four-chamber cine-cardiovascular MR (CMR), is associated with MVO, IMH and convalescent left ventricular (LV) remodelling.54 consecutive patients underwent CMR at 3T (Intera CV, Philips Healthcare, Best, The Netherlands) within 3 days of reperfused STEMI. Cine, T2-weighted, T2* and late gadolinium enhancement (LGE) imaging were performed. Infarct and MVO extent were measured from LGE images. The presence of IMH was investigated by combined analysis of T2w and T2* images. Averaged-MAPSE (medial-MAPSE+lateral-MAPSE/2) was calculated from 4-chamber cine imaging.44 patients completed the baseline scan and 38 patients completed 3-month scans. 26 (59%) patients had MVO and 25 (57%) patients had IMH. Presence of MVO and IMH were associated with lower averaged-MAPSE (11.7±0.4 mm vs 9.3±0.3 mm; p<0.001 and 11.8±0.4 mm vs 9.2±0.3 mm; p<0.001, respectively). IMH (β=-0.655, p<0.001) and MVO (β=-0.567, p<0.001) demonstrated a stronger correlation to MAPSE than other demographic and infarct characteristics. MAPSE ≤10.6 mm demonstrated 89% sensitivity and 72% specificity for the detection of MVO and 92% sensitivity and 74% specificity for IMH. LV remodelling in convalescence was not associated with MAPSE (AUC 0.62, 95% CI 0.44 to 0.77, p=0.22).Postreperfused STEMI, LV longitudinal function assessed by MAPSE can independently predict the presence of MVO and IMH

Acute Reverse Remodelling After Transcatheter Aortic Valve Implantation: A Link Between Myocardial Fibrosis and Left Ventricular Mass Regression

Background: Despite the wealth of data showing the positive effects on cardiac reverse remodelling in the long-term, the immediate effects of transcatheter aortic valve implantation (TAVI) on the left ventricle are yet to be comprehensively described using cardiovascular magnetic resonance imaging. Also, the link between myocardial fibrosis and acute left ventricular (LV) mass regression is unknown. Methods: Fifty-seven patients with severe aortic stenosis awaiting TAVI underwent paired cardiovascular magnetic resonance scans before and early after the procedure (4 [interquartile range, 3-5] days). LV mass, volume, and function were measured. Late gadolinium enhancement (LGE) imaging was performed to assess for the presence of and pattern of myocardial fibrosis. Results: After the procedure, 53 (95%) patients experienced an immediate (10.1 ± 7.1%) reduction in indexed LV mass (LVMi) from 76 ± 15.5 to 68.4 ± 14.7 g/m2 (P < 0.001). Those with no LGE experienced the greatest LVMi regression (13.9 ± 7.1%) compared with those with a midwall/focal fibrosis pattern LGE (7.4 ± 5.8%) and infarct pattern LGE (7.2 ± 7.0%; P = 0.005). There was no overall change in LV ejection fraction (LVEF; 55.1 ± 12.1% to 55.5 ± 10.9%; P = 0.867), however a significant improvement in LVEF was seen in those with abnormal (< 55%; n = 24; 42%) baseline LVEF (43.2 ± 8.9 to 46.7 ± 10.5%; P = 0.027). Baseline LVMi (P = 0.005) and myocardial fibrosis (P < 0.001) were strong independent predictors of early LVMi regression. Conclusions: LV reverse remodelling occurs immediately after TAVI, with significant LV mass regression in the total population and an improvement in LVEF in those with preexisting LV impairment. Those without myocardial fibrosis at baseline experience greater LV mass regression than those with fibrosis

Strong Ultraviolet Pulse From a Newborn Type Ia Supernova

Type Ia supernovae are destructive explosions of carbon oxygen white dwarfs. Although they are used empirically to measure cosmological distances, the nature of their progenitors remains mysterious, One of the leading progenitor models, called the single degenerate channel, hypothesizes that a white dwarf accretes matter from a companion star and the resulting increase in its central pressure and temperature ignites thermonuclear explosion. Here we report observations of strong but declining ultraviolet emission from a Type Ia supernova within four days of its explosion. This emission is consistent with theoretical expectations of collision between material ejected by the supernova and a companion star, and therefore provides evidence that some Type Ia supernovae arise from the single degenerate channel.Comment: Accepted for publication on the 21 May 2015 issue of Natur

Ponatinib (AP24534) inhibits MEKK3-KLF signaling and prevents formation and progression of cerebral cavernous malformations.

Cerebral cavernous malformation (CCM) is a common cerebrovascular disease that can occur sporadically or be inherited. They are major causes of stroke, cerebral hemorrhage, and neurological deficits in the younger population. Loss-of-function mutations in three genes, CCM1, CCM2, and CCM3, have been identified as the cause of human CCMs. Currently, no drug is available to treat CCM disease. Hyperactive mitogen-activated protein kinase kinase Kinase 3 (MEKK3) kinase signaling as a consequence of loss of CCM genes is an underlying cause of CCM lesion development. Using a U.S. Food and Drug Administration-approved kinase inhibitor library combined with virtual modeling and biochemical and cellular assays, we have identified a clinically approved small compound, ponatinib, that is capable of inhibiting MEKK3 activity and normalizing expression of downstream kruppel-like factor (KLF) target genes. Treatment with this compound in neonatal mouse models of CCM can prevent the formation of new CCM lesions and reduce the growth of already formed lesions. At the ultracellular level, ponatinib can normalize the flattening and disorganization of the endothelium caused by CCM deficiency. Collectively, our study demonstrates ponatinib as a novel compound that may prevent CCM initiation and progression in mouse models through inhibition of MEKK3-KLF signaling

A runaway collision in a young star cluster as the origin of the brightest supernova

Supernova 2006gy in the galaxy NGC 1260 is the most luminous one recorded \cite{2006CBET..644....1Q, 2006CBET..647....1H, 2006CBET..648....1P, 2006CBET..695....1F}. Its progenitor might have been a very massive ($>100$ \msun) star \cite{2006astro.ph.12617S}, but that is incompatible with hydrogen in the spectrum of the supernova, because stars $>40$ \msun are believed to have shed their hydrogen envelopes several hundred thousand years before the explosion \cite{2005A&A...429..581M}. Alternatively, the progenitor might have arisen from the merger of two massive stars \cite{2007ApJ...659L..13O}. Here we show that the collision frequency of massive stars in a dense and young cluster (of the kind to be expected near the center of a galaxy) is sufficient to provide a reasonable chance that SN 2006gy resulted from such a bombardment. If this is the correct explanation, then we predict that when the supernova fades (in a year or so) a dense cluster of massive stars becomes visible at the site of the explosion

The utility of global longitudinal strain in the identification of prior myocardial infarction in patients with preserved left ventricular ejection fraction

Prior myocardial infarction (MI) is associated with increased mortality and is prevalent in certain high risk patient groups. Electrocardiogram may be used in diagnosis, however, sensitivity is limited, thus non-invasive imaging techniques may improve diagnosis. We investigated whether global longitudinal strain (GLS) and longitudinal strain parameters are reduced in patients with prior MI but preserved left ventricular ejection fraction (LVEF). The study included 40 clinical patients with prior MI occurring >3 months previously (defined as subendocardial hyperenhancement on late Gadolinium enhancement imaging) with LVEF ≥ 55% and 40 controls matched for age and LVEF. GLS, global longitudinal strain rate (GLSR) and early diastolic longitudinal strain rate (GLSRe) were measured from cine imaging feature tracking analysis. Presence of wall motion abnormality (WMA) and minimum systolic wall thickening (SWT) were calculated from cine imaging. GLS was −17.3 ± 3.7% in prior MI versus −19.3 ± 1.9% in controls (p = 0.012). GLSR was −88.0 ± 33.7%/s in prior MI versus −103.3 ± 26.5%/s in controls (p = 0.005). GLSRe was 76.4 ± 28.4%/s in prior MI versus 95.5 ± 26.0%/s in controls (p = 0.001). GLS accurately identified prior MI [AUC 0.662 (95% CI 0.54–0.785) p = 0.012] whereas WMA [AUC 0.500 (95% CI 0.386–0.614) p = 1.0] and minimum SWT [AUC 0.609 (95% CI 0.483–0.735) p = 0.093] did not. GLS, GLSR and GLSRe are reduced in prior MI with preserved LVEF. Normal LVEF and lack of WMA cannot exclude prior MI. Prior MI should be considered when reduced GLS, GLSR or GLSRe are detected by non-invasive imaging