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3-Dimensional (3D) myocardial deformation analysis (3D-MDA) enables novel descriptions of geometry-independent principal strain (PS). Applied to routine 2D cine cardiovascular magnetic resonance (CMR), this provides unique measures of myocardial biomechanics for disease diagnosis and prognostication. However, healthy reference values remain undefined. This study describes age- and sex-stratified reference values from CMR-based 3D-MDA, including 3D PS. One hundred healthy volunteers were prospectively recruited following institutional ethics approval and underwent CMR imaging. 3D-MDA was performed using validated software. Age- and sex-stratified global and segmental strain measures were derived for conventional geometry-dependent [circumferential (CS), longitudinal (LS), and radial (RS)] and geometry-independent [minimum (minPS) and maximum principal (maxPS)] directions of deformation. Layer-specific contraction angle interactions were determined using local minPS vectors. The average age was 43 ± 15 years and 55% were women. Strain measures were higher in women versus men. 3D PS-based assessment of maximum tissue shortening (minPS) and maximum tissue thickening (maxPS) were greater than corresponding geometry-dependent markers of LS and RS, consistent with improved representation of local tissue deformations. Global maxPS amplitude best discriminated both age and sex. Segmental analyses showed greater strain amplitudes in apical segments. Transmural PS contraction angles were higher in females and showed a heterogeneous distribution across segments. In this study we provided age and sex-based reference values for 3D strain from CMR imaging, demonstrating improved capacity for 3D PS to document maximal local tissue deformations and to discriminate age and sex phenotypes. Novel markers of layer-specific strain angles from 3D PS were also described.

ABSTRACT:Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease caused by mutations in the TTR gene leading to multisystem organ dysfunction. Pathogenic TTR aggregation, misfolding, and fibrillization lead to deposition of amyloid in multiple body organs and frequently involve the peripheral nerve system and the heart. Common neurologic manifestations include: sensorimotor polyneuropathy (PN), autonomic neuropathy, small-fiber PN, and carpal tunnel syndrome. Many patients have significant progression due to diagnostic delays as hATTR PN is not considered within the differential diagnosis. Recently, two effective novel disease-modifying therapies, inotersen and patisiran, were approved by Health Canada for the treatment of hATTR PN. Early diagnosis is crucial for the timely introduction of these disease-modifying treatments that reduce impairments, improve quality of life, and extend survival. In this guideline, we aim to improve awareness and outcomes of hATTR PN by making recommendations directed to the diagnosis, monitoring, and treatment in Canada.

ABSTRACT:Background:Wild-type transthyretin amyloidosis (wtATTR) is an important cause of heart failure (HF); however, the prevalence and clinical significance of neurologic complications remains uncertain.Methods:This analysis reports findings from a single-centre experience of routine neuropathy screening at the time of wtATTR diagnosis by nerve conduction studies and neurologist assessment, compared with age-matched controls.Results:Forty-one wtATTR patients were included, 39 (95%) males, mean age 78.4 ± 7.7 years, 22 (54%) New York Heart Association (NYHA) class III–IV HF, along with 15 age-matched controls (mean age 77.1 ± 4.2 years, 80% male). Twenty-one (51%) wtATTR patients were diagnosed with polyneuropathy, 15 (37%) with spinal stenosis, 36 (88%) with carpal tunnel syndrome (CTS) and 14 (34%) with ulnar neuropathy. Comparison diagnoses among controls were 1 (7%), 0, 1 (7%) and 3 (20%), respectively. Among patients with NYHA class III–IV HF, 16 (73%) had polyneuropathy compared with 5 (26%) with class I–II (p < 0.01), odds ratio of 7.5 (95% confidence interval 1.9–29.9). After neuropathy screening, 19 (46%) patients were offered neurologic therapy and/or additional diagnostic evaluation. This included CTS release surgery (16, 39%), neuropathic pain medication (3, 7%), nerve block (1, 2%), wrist splinting (2, 5%) and foot care (1, 2%). Spine imaging was performed for 3 (7%) patients, and deltoid muscle and sural nerve biopsy for 1 (2%) patient.Conclusions:Screening of wtATTR patients for neurologic complications resulted in a management change for nearly half. CTS, polyneuropathy and ulnar neuropathy were common. This approach warrants consideration as part of routine assessment for newly diagnosed wtATTR patients.

Cardiac allograft vasculopathy (CAV) is an important adverse prognostic factor for pediatric heart transplant (HT) recipients. Invasive coronary angiography (ICA) is the gold standard for CAV detection but lacks sensitivity for early microvascular changes and cumulative radiation exposure is of concern. Real-time myocardial contrast echocardiography (RTMCE) using ultrasound enhancing (contrast) agents performed during dobutamine stress echocardiography (DSE) can assess myocardial function, perfusion, and microvascular integrity. The objective of this study was to determine the safety and feasibility of RTMCE during DSE to detect CAV in a pediatric HT population.

Cardiac amyloidosis is an emerging and important cause of heart failure, arrhythmia, and other cardiovascular disease in Canada. In this context, many centres have expressed interest in the development of effective care pathways for screening, evaluating, and treating this rapidly growing patient population. In October 2019, a group of Canadian stakeholders met, including specialists in cardiac amyloidosis, experts in heart failure and chronic disease management, and academic and community-based cardiologists at various stages of cardiac amyloidosis clinic development. Objectives of the meetings included discussion of existing care pathways, consideration of barriers to program development, and achieving a consensus on essential and desirable components of a best-practice cardiac amyloidosis program. Topics discussed included optimal settings for cardiac amyloidosis clinics and integration with other specialty clinics, funding limitations that act as barriers to program development and potential solutions to these barriers, the roles of the multidisciplinary team and specialist physicians in amyloidosis care, and diagnostic pathways and strategies for the identification of patients with cardiac amyloidosis. In this report, we summarize the discussion points and key recommendations for the development of a cardiac amyloidosis clinic that emerged from this meeting, focused on program integration and care coordination, human resource elements, access to care, and quality improvement and outcome measures in cardiac amyloidosis.

Right heart function is an important prognostic determinant in cardiac amyloidosis. In this study we characterized serial changes in right and left heart function and evaluated their prognostic significance.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a life-threatening, progressive, infiltrative disease caused by the deposition of transthyretin amyloid fibrils in the heart, and can often be overlooked as a common cause of heart failure. Delayed diagnosis due to lack of disease awareness and misdiagnosis results in a poorer prognosis. Early accurate diagnosis is therefore key to improving patient outcomes, particularly in the context of both the recent approval of tafamidis in some countries (including the United States) for the treatment of ATTR-CM, and of other promising therapies under development. With the availability of scintigraphy as an inexpensive, noninvasive diagnostic tool, the rationale to screen for ATTR-CM in high-risk populations of patients is increasingly warranted. Here the authors propose a framework of clinical scenarios in which screening for ATTR-CM is recommended, as well as diagnostic “red flags” that can assist in its diagnosis among the wider population of patients with heart failure.

Pulmonary arterial hypertension (PAH) can cause maladaptive right ventricular (RV) functional changes associated with adverse prognosis that are challenging to accurately quantify noninvasively. The aim of this study was to explore principal strain (PS) with contraction angle analysis using three-dimensional echocardiography to characterize RV deformation changes in patients with PAH.

Multi-phase Computed Tomography Angiography (mpCTA) is routinely performed prior to transcatheter aortic valve replacement (TAVR) to determine eligibility and enable pre-procedural planning. Incremental prognostic value may be realized from full-cycle, multi-phase reconstructions to assess the contractile health of cardiac chambers. This study aimed to assess the feasibility of 4D chamber modelling of the left ventricle (LV) to support 3D minimum principal strain (3DminPS) based predictions of clinical outcomes following TAVR.

The diagnosis of cardiac amyloidosis can be challenging because it is regarded as a rare disease, frequently presents with nonspecific signs and symptoms, and there are a variety of diagnostic tests available. Approaches for the evaluation of patients with suspected cardiac amyloidosis have improved dramatically in recent years. The initial workup is similar to all patients with heart failure, and certain findings on routine investigations may heighten the index of suspicion. Laboratory testing to screen for light chain (AL) amyloidosis must be performed in all patients, prompting further hematologic assessment if abnormalities are identified. Nuclear scintigraphy with bone-seeking radiotracer has emerged as an effective technique for diagnosing cardiac transthyretin amyloidosis (ATTR) noninvasively. Patients with ATTR cardiac amyloidosis should be referred for genetic testing to confirm or exclude a transthyretin gene mutation. Endomyocardial biopsy remains the diagnostic gold standard and should be performed if the evaluation yields equivocal or discordant findings; however, this is becoming necessary less often, owing to the improved diagnostic yield of noninvasive cardiac imaging modalities. As a result, patients may be diagnosed at earlier stages of disease, potentially improving their likelihood of response to therapy and overall prognosis.

Recent developments in cardiac amyloidosis have raised awareness of the disease and have advanced diagnostic and treatment strategies. Novel therapies may vastly improve the prognosis of the disease but will be associated with significant costs. Data are needed to inform clinical decisions and to drive resource allocation within the health care system. Many aspects of disease management are unlikely to be addressed by clinical trials and are better suited to nonrandomized cohort studies, but the limited numbers of patients in any single centre present barriers to high-quality observational research. Disease registries offer opportunities to assemble large numbers of patients from multiple institutions for adequately powered observational studies, to recruit patients for randomized clinical trials; to provide real-world effectiveness and safety data, to study cost-effectiveness of novel therapies, and to engage patients in the collection of patient-reported outcome data. Existing amyloidosis registries have limitations. Canada is an ideal setting for a national amyloidosis registry, with ethnic diversity, relatively few academic centres, access to advanced diagnostic and therapeutic options, and a track record of collaboration among institutions. The Canadian Registry for Amyloidosis Research aims to capitalize on this opportunity and provide high-quality data to inform clinical practice and health care policy in Canada and beyond.

Right ventricular (RV) strain imaging using speckle-tracking echocardiography (STE) is a quantitative method of assessing RV systolic function that has shown prognostic utility in patients with pulmonary hypertension (PH). However, its prognostic value for a large and mixed PH population remains poorly defined.

The mammalian target of rapamycin (mTOR) inhibitors sirolimus and everolimus are increasingly used in cardiothoracic transplantation. Several recent clinical trials have demonstrated their efficacy in combination with reduced cyclosporine dosing in de novo heart transplant recipients, in particular with everolimus. A number of other studies have demonstrated their efficacy for improving renal function and reducing calcineurin inhibitor use, attenuating cardiac allograft vasculopathy progression and reducing cytomegalovirus infections in maintenance heart transplant populations. A growing body of literature, including a small number of clinical trials, now describes the use mTOR inhibitors in lung transplant recipients. The benefits in this population include improved lung and renal function in limited studies. Considerably less evidence is available in pediatric heart transplantation, though similar indications in the maintenance therapy population have been described. The benefits of mTOR inhibitors must be weighed against the increased risk of adverse events and drug intolerance compared with other primary immunosuppressants, and discontinuation rates are particularly high in lung transplant recipients. The risks of surgical wound healing complications in transplant recipients receiving mTOR inhibitors previously or actively supported by mechanical circulatory support devices remains poorly described in the current literature. The current role and recent evidence for mTOR inhibitor use in heart and lung transplantation is examined in this review.The overview summarizes the growing body of data regarding the use of mammalian target of rapamycin inhibitors in cardiothoracic transplantation. The beneficial effects on acute rejection, renal function and cardiac vasculopathy should be balanced against the adverse events and the increasing complexity of the recipients.

Modern treatment strategies have led to improvements in cancer survival, however, these gains might be offset by the potential negative effect of cancer therapy on cardiovascular health. Cardiotoxicity is now recognized as a leading cause of long-term morbidity and mortality among cancer survivors. This guideline, authored by a pan-Canadian expert group of health care providers and commissioned by the Canadian Cardiovascular Society, is intended to guide the care of cancer patients with established cardiovascular disease or those at risk of experiencing toxicities related to cancer treatment. It includes recommendations and important management considerations with a focus on 4 main areas: identification of the high-risk population for cardiotoxicity, detection and prevention of cardiotoxicity, treatment of cardiotoxicity, and a multidisciplinary approach to cardio-oncology. All recommendations align with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Key recommendations for which the panel provides a strong level of evidence include: (1) that routine evaluation of traditional cardiovascular risk factors and optimal treatment of preexisting cardiovascular disease be performed in all patients before, during, and after receiving cancer therapy; (2) that initiation, maintenance, and/or augmentation of antihypertensive therapy be instituted per the Canadian Hypertension Educational Program guidelines for patients with preexisting hypertension or for those who experience hypertension related to cancer therapy; and (3) that investigation and management follow current Canadian Cardiovascular Society heart failure guidelines for cancer patients who develop clinical heart failure or an asymptomatic decline in left ventricular ejection fraction during or after cancer treatment. This guideline provides guidance to clinicians on contemporary best practices for the cardiovascular care of cancer patients.

A 54-year-old man with the lysosomal storage disorder Anderson-Fabry disease (AFD) and cardiac involvement was placed on amiodarone for treatment of symptomatic paroxysmal atrial fibrillation. Shortly thereafter, he developed symptoms of acute decompensated heart failure, requiring hospital admission. Endomyocardial biopsy demonstrated findings consistent with AFD and possible amiodarone toxicity. Amiodarone was discontinued, and the patient’s heart failure resolved with return to baseline status. Amiodarone is known to alter lysosomal pH and enzyme activity, and this case illustrates how it should be used with considerable caution in patients with AFD.

Introduction:The respective value of different late gadolinium enhancement (LGE) phenotypes in patients with suspected infiltrative cardiomyopathy remains uncertain.Methods:In a large cohort of patients referred for suspected infiltrative cardiomyopathy, we evaluated respective associations between the dominant LGE phenotype and the composite endpoint of heart failure hospitalization, survived cardiac arrest or death. Kaplan-Meier survival curves were executed for six pre-defined LGE phenotypes. Multivariable analysis was performed to assess their independent association with the composite outcome, adjusted for relevant confounders. Final diagnosis was adjudicated using standardized disease-specific criteria.Results:588 patients (68% male, median age 70 years, mean LVEF 54.7±12.7%) were studied. Of these patients, 139 (24%) were confirmed to have cardiac amyloidosis (CA) (81 [58%] transthyretin, 54 [39%] light chain and 4 [3%] undifferentiated) by objective non-CMR diagnostic criteria. Any LGE was present in 394 patients (67%) with the dominant phenotype being diffuse in 137 (23%), mid-wall patchy in 118 (20%), ischemic in 55 (9.4%), subepicardial in 18 (3.1%), mid-wall striae in 8 (1.4%), and RV insertion site in 58 (9.9%). The sensitivity and specificity of diffuse LGE for CA was 86% and 96%, respectively. Over a median 855 (IQR 372, 1542) days, 239 (41%) experienced the primary outcome. Unadjusted survival curves for each LGE phenotype are shown in the Figure. Following adjustment, diffuse (HR 2.30, p<0.001), mid-wall patchy (HR 1.52, p=0.040) and ischemic LGE (HR 1.78, p=0.023) remained independently associated (Figure).Conclusions:In patients referred for suspected infiltrative cardiomyopathy, diffuse, mid-wall patchy and ischemic patterns all showed independent prognostic value. We confirm that diffuse LGE pattern reliably identifies CA patients with high sensitivity and specificity while delivering strong prognostic value.

Acute allograft dysfunction (AAD) is an important cause of morbidity among heart transplant recipients. The role of donor-specific antibodies (DSAs) in AAD, with the increasing use of single antigen bead (SAB) assays that have improved the ability to detect DSA, remains unclear.

Late gadolinium enhancement-cardiac magnetic resonance is increasingly performed in patients with systolic dysfunction. Numerous patterns of fibrosis are commonly reported among this population. However, the relative prevalence and prognostic significance of these findings remains uncertain.

To determine the frequency and prognostic significance of abnormal exercise echocardiographic results for patients achieving a workload of 10 or more metabolic equivalents during treadmill exercise echocardiography.

Although right ventricular (RV) dysfunction is a major determinant of outcome in patients with pulmonary hypertension (PH), the optimal measure of RV function is poorly defined. We hypothesized that RV strain measured by speckle-tracking echocardiography predicts outcome in PH over a broad range of pulmonary pressures.

Sudden cardiac death (SCD) and sustained monomorphic ventricular tachycardia (SMVT) are frequently associated with prior or acute myocardial injury. Cardiovascular magnetic resonance (CMR) provides morphological, functional, and tissue characterization in a single setting. We sought to evaluate the diagnostic yield of CMR-based imaging versus non–CMR-based imaging in patients with resuscitated SCD or SMVT.

Ojectives. Interleukin-6 (IL-6) exerts multiple effects on chondrocytes and fibroblasts within the joint and is associated with disease activity in juvenile idiopathic arthritis (JIA). Although these cells express the ubiquitous signalling receptor for all IL-6-related cytokines, gp130, they do not express a cognate IL-6 receptor. Consequently, IL-6 responses within these cells occur via IL-6 trans-signalling relying on the presence of a soluble receptor (sIL-6R). Levels of sIL-6R in vivo are governed by either proteolytic cleavage (PC) of cognate receptor or by differential sIL-6R mRNA splicing (DS). The aim of this study was to evaluate the contribution of both isoforms to clinical parameters associated with IL-6 signalling in JIA.Methods. IL-6, sIL-6R and DS-sIL-6R were measured by ELISA in serum and synovial fluid (SF) samples from 86 JIA patients. These data were related to indicators of inflammation-erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and compared between patients stratified by subtype, age and disease duration.Results. SF IL-6 significantly correlated with general indicators of activity (ESR and CRP) and SF PC-sIL-6R to a lesser degree with CRP. When the IL-6:sIL-6R ratio was calculated as an indicator of the potential for IL-6 signalling within the joint, 33% of SF samples showed a ratio >1 indicating saturation of sIL-6R by IL-6. Mean DS-sIL-6R levels were 0.71 ng/ml, whereas PC-sIL-6R levels constituted the majority of sIL-6R at 20.89 ng/ml.Conclusions. IL-6 trans-signalling within the joints of JIA patients is predominantly governed by the presence of PC-sIL-6R, and the data provided suggest that synovial levels of IL-6 and sIL-6R would be sufficient to drive IL-6 responses in chondrocytes and synovial fibroblasts.

A clone encoding thyroid hormone receptor-β (TR-β) was isolated from a sea bream (Sparus aurata) ovary cDNA library. Sea bream (sb)TR-β is closely related to its counterparts from other vertebrates and, like them, preferentially binds T3 rather than T4. However, the putative sbTR-β protein contains a nine-amino-acid insert that is also present in the corresponding proteins from flounder and salmon but absent in TR-βs from zebrafish and terrestrial vertebrates. Semiquantitative RT–PCR analysis showed that sbTR-β transcripts begin to accumulate during gastrulation and increase markedly in quantity up to the period around hatch (ca. 40 h postfertilization) before declining slightly. In adult tissues, TR-β mRNA was present in approximately equal quantities in heart, intestine, brain, kidney, skeletal muscle, liver, and gill. The significance of the relatively strong expression of TR-β during sea bream embryogenesis is discussed.

Reinfection with hookworm (Necator americanus) following chemotherapy was studied over 8 years in a rural village in Madang Province, Papua New Guinea. Faecal egg counts were performed on up to 202 individuals in July 1988, August 1990 and November 1996; the study population was treated after sampling in 1988 and 1990. Reinfection burdens in 1996 did not differ significantly from pretreatment burdens (in 1988), and were significantly higher than burdens in 1990. However, the prevalence of hookworm infection was significantly lower in 1996 than in either 1988 or 1990. There was significant predisposition to high or low hookworm burden between 1990 and 1996; this predisposition was stronger in children than adults. However, there was no detectable predisposition between 1988 and 1996 in individuals who had been treated 2 or more times between surveys. The mean weight of adult hookworms in individual hosts was measured in 1988 and 1990 using worms expelled after chemotherapy. There was a significant positive correlation between mean male hookworm weight in the 2 years, suggesting that individual hosts are predisposed to infection with heavy or light hookworms. These data suggest that differences in host susceptibility are involved in generating predisposition, but that longer-term variation in either exposure or susceptibility limits the period over which significant predisposition can be detected.

Introduction:Initial clinical manifestations of transthyretin amyloidosis (ATTR) are not well understood, making timely diagnosis challenging. Methods:Patients aged ≥68 years newly diagnosed with ATTR were identified using Medicare Research Identifiable Files. Symptom manifestation and healthcare utilization were measured during 3 years pre-diagnosis; demographics and comorbidity index during 1-year pre-diagnosis. Controls (ATTR-free) were matched 1:1 to patients with ATTR based on age, sex and region; same index date and enrollment as match. Results:We identified 552 matched ATTR-control pairs: mean age 78.3 (standard deviation 6.3) and 64.5% male. Among patients with ATTR (vs controls), cardiovascular conditions (92.9 vs 75.9%) and hospitalization (54.0 vs 35.5%) were frequent during 3 years pre-diagnosis. Conclusion:Patients with ATTR have multiple symptoms and hospitalizations pre-diagnosis, recognition of which may facilitate earlier diagnosis and treatment.

Three cases of giant cystic craniopharyngiomas with large areas of extension beyond the suprasellar area are presented. The magnetic resonance (MR) appearance in one case is described. These giant tumors had large, multilobulated cysts that comprised the bulk of the tumors. In one case, there was an unusual extension of the large tumor cyst into the lateral ventricle. In two cases, the tumors extended to the level of the foramen magnum. On CT, the cyst contents of these two tumors were hyperdense and became hypodense postoperatively. All three tumors harbored calcifications in the form of clumps in the suprasellar region and rim calcifications around the cysts. None of the tumors exhibited contrast enhancement. A literature review of the radiographic features of craniopharyngiomas is discussed.

Fast low-angle multiecho (FLAME) imaging uses partial flip angles of 90dG with 180dG radiofrequency refocusing pulses. The partial flip angle permits imaging with shorter repetition time (TR) values on the order of 750–1,000 ms for 30dG angles with image contrast characteristics identical to those obtained with conventional 90–180dG schemes and TRs on the order of 2,500 ms. The approximately threefold reduction in imaging time is accompanied by a decrease in signal-to-noise ratio. In many circumstances, however, this trade-off may produce entirely acceptable images of the CNS at a significant reduction in imaging time.

This paper reviews the current status of nematodes with stress-inducible transgenes as biosensors responsive to a range of external stressors, e.g., soil or water pollution, microwave radiation or immunological attack. TransgenicCaenorhabditis eleganscarrying reporter genes under heat shock promoter control express reporter products only under stressful conditions. Although relatively insensitive to single metal ions, these worms respond to complex mixtures present in metal-contaminated watercourses and to laboratory mixtures containing similar constituents, but not to any of their components singly at comparable concentrations. Responses to metal mixtures are enhanced by a non-ionic surfactant, Pluronic F-127. Metals taken up by food bacteria and insoluble metal carbonates can also evoke stress responses, both in soil and aqueous media. However, high concentrations of added metals are needed to induce clear-cut responses in soil, owing to metal sorption onto clays and organic matter. Transgenic worms are also stressed by exposure to microwave radiation; pulsed signals generate responses that diminish markedly with distance from the source. Finally, stress responses are inducible by anti-epicuticle antisera and complement, suggesting that immune attack can also activite the heat shock system. The development of rapid microplate toxicity assays based on transgenic nematodes is discussed.

The advent of newly available medical therapies for heart failure with reduced ejection fraction (HFrEF) has resulted in many potential therapeutic combinations, increasing treatment complexity. Publication of expert consensus guidelines and initiatives aimed to improve implementation of treatment has emphasized sequential stepwise initiation and titration of medical therapy, which is labour intensive. Data taken from heart failure registries show suboptimal use of medications, prolonged titration times, and consequently little change in dose intensity, all of which indicate therapeutic inertia. Recently published evidence indicates that 4 medication classes—renin-angiotensin-neprilysin inhibitors, β-blockers, mineralocorticoid antagonists, and sodium-glucose cotransporter inhibitors—which we refer to as Foundational Therapy, confer rapid and robust reduction in both morbidity and mortality in most patients with HFrEF and that they work in additive fashion. Additional morbidity and mortality may be observed following addition of several personalized therapies in specific subgroups of patients. In this review, we discuss mechanisms of action of these therapies and propose a framework for their implementation, based on several principles. These include the critical importance of rapid initiation of all 4 Foundational Therapies followed by their titration to target doses, emphasis on multiple simultaneous drug changes with each patient encounter, attention to patient-specific factors in choice of medication class, leveraging inpatient care, use of the entire health care team, and alternative (ie, virtual visits) modes of care. We have incorporated these principles into a Cluster Scheme designed to facilitate timely and optimal medical treatment for patients with HFrEF.

Electron Backscatter Diffraction (EBSD) has shown great utility in characterizing the aspects of microstructure related to crystallographic orientation. Such information is critical to understanding deformation in crystalline materials as well as the impact of deformation induced structural variations on recrystallization. Small angle rotations induced by the production of dislocations and their movement through the structure can be well captured by EBSD. Geometrically Necessary Dislocations (GND) can be derived from the measurement of these local variations in orientation. However, these local orientation variations are often right at the limit of angular precision that can be achieved by EBSD. Various post-processing tools have been developed to improve the angular precision. However, this is generally achieved through point-to-point smoothing of the orientation data within the measurement grid. The impact of such various filtering method are explored in terms of their impact on GND calculations. A new post processing approach which improves the EBSD indexing rate will also be presented along with results on its influence on local orientation variations. Fortunately, the general conclusion drawn from the reduction results is that these approaches generally improve the overall GND measurements.

A newborn female child with hypothermia, tachypnoea and poor Agpar scores was demonstrated to have absent septum pellucidum, partial agenesis of the corpus callosum and misshapen left lateral ventricle on ultrasound examination. Fundoscopic examination noted hypoplastic optic discs. Given the appropriate clinical setting and fundoscopic examination, cranial ultrasound can be the preliminary evaluation for septo-optic dysplasia and related anomalies in infants with open fontanelles.