An approach to reporting paediatric leukoencephalopathy and leukodystrophies.

The leukodystrophies (LD) and leukoencephalopathies (LE) are a diverse group of conditions involving the cerebral white and grey matter. There is heterogeneity in the clinical presentations, imaging features, and biochemical dysfunction. Given the number of conditions and varied imaging appearances, this topic can be difficult for non-specialist radiologists who do not routinely work in dedicated paediatric neuroradiology centres. This article will aim to provide a simplified and step-wise approach to assessing suspected LD/LE, focussing on the more common diagnoses you may encounter in the UK. Additionally, it will highlight important non-LD/LE differentials, which if considered early, may significantly alter treatment and prognosis. By the end of this review, we hope the reader will begin to develop an awareness of physiological paediatric brain development in terms of normal myelination; the ability to recognise and categorise the distribution of abnormal signal based on the established diagnostic framework outlined by Schiffmann & Van der Knapp; and be aware of potential non-LD/LE radiological mimics.

Evidence of altered fatty acid metabolism in dogs with naturally occurring valvular heart disease and congestive heart failure.

INTRODUCTION: Myxomatous mitral valve disease (MMVD) is the most common cardiac condition in adult dogs. The disease progresses over several years and affected dogs may develop congestive heart failure (HF). Research has shown that myocardial metabolism is altered in cardiac disease, leading to a reduction in ß-oxidation of fatty acids and an increased dependence upon glycolysis. OBJECTIVES: This study aimed to evaluate whether a shift in substrate use occurs in canine patients with MMVD; a naturally occurring model of human disease. METHODS: Client-owned dogs were longitudinally evaluated at a research clinic in London, UK and paired serum samples were selected from visits when patients were in ACVIM stage B1: asymptomatic disease without cardiomegaly, and stage C: HF. Samples were processed using ultra-performance liquid chromatography mass spectrometry and lipid profiles were compared using mixed effects models with false discovery rate adjustment. The effect of disease stage was evaluated with patient breed entered as a confounder. Features that significantly differed were screened for selection for annotation efforts using reference databases. RESULTS: Dogs in HF had altered concentrations of lipid species belonging to several classes previously associated with cardiovascular disease. Concentrations of certain acylcarnitines, phospholipids and sphingomyelins were increased after individuals had developed HF, whilst some ceramides and lysophosphatidylcholines decreased. CONCLUSIONS: The canine metabolome appears to change as MMVD progresses. Findings from this study suggest that in HF myocardial metabolism may be characterised by reduced ß-oxidation. This proposed explanation warrants further research.

Anterior mitral valve leaflet length in cats with hypertrophic cardiomyopathy.

INTRODUCTION: Anterior mitral valve leaflet (AMVL) elongation is a recognised feature of hypertrophic cardiomyopathy (HCM). However, whether AMVL elongation precedes left ventricular hypertrophy in cats is currently unknown. The aim of this study was to explore the risk of developing an HCM phenotype in cats with an elongated AMVL. ANIMALS: FIFTY-FIVE APPARENTLY HEALTHY CATS WITH A NORMAL BASELINE ECHOCARDIOGRAM AND A FOLLOW-UP ECHOCARDIOGRAM AT >ONE YEAR. MATERIALS AND METHODS: This was a retrospective longitudinal study. Cats at the baseline were grouped based on whether or not they developed an HCM phenotype at follow-up. AMVL length and left atrial and left ventricular dimensions were measured from two-dimensional images. RESULTS: The median follow-up period of the study population was 5.4 years (25th and 75th quartile, 2.7-6.7 years). During this time, 17 cats (30.9%) developed an HCM phenotype. At the baseline, cats that subsequently developed an HCM phenotype had greater AMVL length (9.4 mm [25th and 75th quartile, 9.0-10.6 mm] vs. 8.5 mm [25th and 75th quartile, 7.6-9.1 mm], P < 0.0001) and maximal left ventricular wall thickness (4.5 mm [25th and 75th quartile, 4.1-4.7 mm] vs. 4.0 mm [25th and 75th quartile, 3.7-4.6 mm], P = 0.007) than those that did not. Multiple logistic regression analysis confirmed that both baseline variables were independent predictors for development of an HCM phenotype. CONCLUSIONS: The AMVL length was greater in cats that subsequently developed left ventricular hypertrophy. Further studies investigating the clinical application of AMVL in the natural history of feline HCM are warranted.

Paroxysmal high-grade second-degree and persistent third-degree atrioventricular block in cats.

INTRODUCTION: Both paroxysmal high-grade second-degree and persistent third-degree atrioventricular block (AVB) are recognised in cats. Our aim was to document the presentation, echocardiographic data, comorbidities and outcome in affected cats from a single referral hospital, including those that underwent epicardial pacemaker implantation (EPI). ANIMALS, MATERIALS AND METHODS: This retrospective study included 64 cats diagnosed with persistent third-degree or paroxysmal high-grade AVB, for which detailed patient history was available. Non-parametric testing, Kaplan-Meier curves and Cox proportional hazard testing were performed. RESULTS: Atrioventricular block was persistent in 43 cats (67%) and paroxysmal in 21 (33%). Forty-seven cats (74%) were referred for cardiac complaints (e.g. collapse, arrhythmia, tachypnea), 6 (9%) had non-specific complaints and AVB was an incidental finding in 11 cats (17%). Median duration of clinical signs prior to presentation was 21 days (1-1138 days). Thirty-nine (63%) cats had echocardiographic abnormalities; 13 (20%) presented with congestive heart failure. Forty-five (70%) cats had one or more comorbidities. Fifteen cats underwent EPI with immediate resolution of signs in 12 cats. Following EPI, two and four cats experienced major and minor complications, respectively. Forty-seven cats died; median survival time was 799 days (all-cause mortality). Cardiac-related death occurred in 17 cats (36%); median survival in these cats was 132 days. Heart failure on presentation was the only independent risk factor for cardiac death (p=0.002). CONCLUSIONS: Outcome in cats with AVB was variable, although most had good medium- to long-term survival. Cardiac death occurred in a minority of cats. Pacemaker implantation was effective in relieving clinical signs.

Review of the MRI brain findings of septo-optic dysplasia.

AIM: To report the magnetic resonance imaging (MRI) findings from a retrospective case analysis of children with septo-optic dysplasia (SOD), a rare congenital disorder characterised by any combination of midline brain defects, optic nerve hypoplasia (ONH), and hypothalamic-pituitary dysfunction. MATERIALS AND METHODS: SOD was defined radiologically as complete or partial septum pellucidum (SP) absence with hypoplasia of at least one of the optic nerves and/or chiasm. Local MRI databases were searched for SOD cases in children over an 18-year period, and studies reviewed by two consultant paediatric neuroradiologists. The extent of structural SP, optic nerve, chiasm, and hypothalamic-pituitary involvement was recorded, along with coexisting brain abnormalities. RESULTS: Forty-eight cases of SOD were found; 44/48 (92%) demonstrated complete SP absence whereas 4/48 (8%) had partial absence. Eight of 48 cases (17%) exhibited unilateral ONH. Fifty-one percent of cases, where the pituitary was identified on MRI, demonstrated a structural pituitary abnormality, which included an ectopic posterior bright spot in 6%. The olfactory nerves were hypoplastic in 5/48 cases (10%). Twenty-seven of the 48 cases (56%) had another brain abnormality, resulting from some form of cortical formation abnormality/schizencephaly in 21/48 (44%). CONCLUSION: A high rate of associated brain abnormalities was found in the present cohort, including structural pituitary abnormalities in 51% and cortical formation abnormalities/schizencephaly in 44%. This suggests there is not a single cause for SOD, rather SOD is the phenotypic end point from multiple aetiological events. Individual children with SOD may have coexisting intracranial abnormalities, and, hence, high-quality MRI is required in all.

Transient Myocardial Thickening in Cats Associated with Heart Failure.

BACKGROUND: Cats with hypertrophic cardiomyopathy (HCM) and congestive heart failure (CHF) can have resolution of both left ventricular hypertrophy and CHF. OBJECTIVES: To describe the clinical characteristics of cats with transient myocardial thickening (TMT) and CHF compared with a control population of cats without resolution of HCM. ANIMALS: A total of 21 cats with TMT, 21 cats with HCM. METHODS: Retrospective study. Clinical records at 4 veterinary centers were searched for TMT cases and a control group of cats with HCM and CHF. TMT was defined as initial maximal left ventricular wall thickness (LVWT) ≥6 mm with left-sided CHF, with subsequent resolution of CHF, reduction in left atrium/aorta (LA/Ao), and LVWT<5.5 mm. HCM was defined as persistent LVWT ≥6 mm. RESULTS: Cats with TMT were younger (2 [0.4-11.4] years) than cats with HCM (8 [1.6-14] years) (P < 0.0001), and antecedent events were more common (15/21 versus 6/21, respectively) (P = 0.01). In cats with TMT, LVWT normalized from 6.8 [6.0-9.7] mm to 4.8 [2.8-5.3] mm and LA/Ao decreased from 1.8 [1.6-2.3] to 1.45 [1.2-1.7] after a mean interval of 3.3 (95% CI: 1.8-4.7) months. CHF recurred in 1 of 21 TMT and 15 of 21 cats with HCM. Cardiac treatment was discontinued in 20 of 21 cats with TMT and 0 of 21 HCM cats. All cats with TMT survived, whereas 8 of 19 cats with HCM died during the study period. CONCLUSIONS AND CLINICAL IMPORTANCE: TMT occurs in younger cats, and antecedent events are common. The prognosis is better in cats with CHF associated with TMT than HCM.

Anatomical subgroup analysis of the MERIDIAN cohort: failed commissuration.

OBJECTIVE: To assess the contribution of fetal magnetic resonance imaging (MRI) in fetuses of the MERIDIAN cohort diagnosed with either agenesis or hypogenesis of the corpus callosum (referred to collectively as failed commissuration) on antenatal ultrasound. METHODS: This was a subgroup analysis of the MERIDIAN study of fetuses with failed commissuration (with or without ventriculomegaly) diagnosed on ultrasound in women who had MRI assessment within 2 weeks of ultrasound and for whom outcome reference data were available. The diagnostic accuracy of ultrasound and MRI was studied, as well as indicators of diagnostic confidence and effects on prognosis/clinical management. Appropriate diagnostic confidence was assessed by the score-based weighted average method, which combines diagnostic accuracy with diagnostic confidence data. RESULTS: In the MERIDIAN cohort, 79 fetuses were diagnosed with failed commissuration on ultrasound (55 with agenesis and 24 with hypogenesis of the corpus callosum). The diagnostic accuracy for detecting failed commissuration was 34.2% for ultrasound and 94.9% for MRI (difference, 60.7% (95% CI, 47.6-73.9%), P < 0.0001). The diagnostic accuracy for detecting hypogenesis of the corpus callosum as a discrete entity was 8.3% for ultrasound and 87.5% for MRI, and for detecting agenesis of the corpus callosum as a distinct entity was 40.0% for ultrasound and 92.7% for MRI. There was a statistically significant improvement in 'appropriate' diagnostic confidence when using MRI as assessed by the score-based weighted average method (P < 0.0001). Prognostic information given to the women changed in 36/79 (45.6%) cases after MRI and its overall effect on clinical management was 'significant', 'major' or 'decisive' in 35/79 cases (44.3%). CONCLUSIONS: Our data suggest that any woman whose fetus has failed commissuration as the only intracranial finding detected on ultrasound should have MRI examination for further evaluation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Mitral Annular Plane Systolic Excursion and Tricuspid Annular Plane Systolic Excursion in Cats with Hypertrophic Cardiomyopathy.

BACKGROUND: Left ventricular (LV) systolic dysfunction is associated with increased risk of death in cats with hypertrophic cardiomyopathy (HCM). Mitral and tricuspid annular plane systolic excursion (MAPSE and TAPSE, respectively) are measures of longitudinal systolic function and are reduced in human patients with HCM. HYPOTHESES: Cats with HCM have lower MAPSE and TAPSE compared to control cats; lower MAPSE and TAPSE are associated with the presence of congestive heart failure (CHF) and reduced survival time. ANIMALS: 64 cats with HCM and 27 healthy cats. Forty-five cats with HCM were not showing clinical signs, and 19 had CHF. METHODS: Retrospective study. Anatomic M-mode from the left apical 4-chamber view was used to record MAPSE from the free wall (MAPSE FW) and septum (MAPSE IVS) and TAPSE. RESULTS: Compared to controls, cats with HCM had lower MAPSE IVS (controls 5.2 [4.6-5.6] mm, asymptomatic HCM 4.7 [4.1-5.2] mm, HCM with CHF 2.6 [2.5-3.2] mm, P < .001), MAPSE FW (controls 5.9 [5.3-6.2] mm, asymptomatic HCM 4.7 [4.1-5.1] mm, HCM with CHF 2.8 [2.4-3.2] mm) and TAPSE (controls 8.6 [7.4-10.2] mm, asymptomatic HCM 7.2 [6.3-8.2] mm, HCM with CHF 4.6 [4.1-5.4] mm), with the lowest in the CHF group. Univariate survival analysis showed a shorter survival in cats displaying lower MAPSE IVS, MAPSE FW, and TAPSE. CONCLUSIONS AND CLINICAL IMPORTANCE: MAPSE and TAPSE were lower in cats with HCM than in control cats and were lowest in CHF, suggesting that systolic longitudinal dysfunction is present in cats with HCM. MAPSE and TAPSE have potential prognostic significance.

Anatomical subgroup analysis of the MERIDIAN cohort: posterior fossa abnormalities.

OBJECTIVE: To assess the diagnostic and clinical contribution of fetal magnetic resonance imaging (MRI) in fetuses of the MERIDIAN cohort diagnosed with abnormalities of the posterior fossa as the only intracranial abnormality recognized on antenatal ultrasound. METHODS: This was a subgroup analysis of the MERIDIAN study of fetuses with abnormalities of the posterior fossa (with or without ventriculomegaly) diagnosed on antenatal ultrasound in women who had MRI within 2 weeks of ultrasound and for whom outcome reference data were available. The diagnostic accuracy of ultrasound and MRI is reported, as well as indicators of diagnostic confidence and effects on prognosis and clinical management. Appropriate diagnostic confidence was assessed by the score-based weighted average method, which combines diagnostic accuracy with diagnostic confidence data. RESULTS: Abnormalities confined to the posterior fossa according to ultrasound were found in 81 fetuses (67 with parenchymal and 14 with cerebrospinal fluid-containing lesions). The overall diagnostic accuracy for detecting an isolated posterior fossa abnormality was 65.4% for ultrasound and 87.7% for MRI (difference, 22.3% (95% CI, 14.0-30.5%); P < 0.0001). There was an improvement in 'appropriate' diagnostic confidence, as assessed by the score-based weighted average method (P < 0.0001), and a three-fold reduction in 'high confidence but incorrect diagnosis' was achieved using MRI. Prognostic information given to the women changed after MRI in 44% of cases, and the overall effect of MRI on clinical management was considered to be 'significant', 'major' or 'decisive' in 35% of cases. CONCLUSIONS: Our data suggest that any woman whose fetus has a posterior fossa abnormality as the only intracranial finding on ultrasound should have MRI for further evaluation. This is on the basis of improved diagnostic accuracy and confidence, which impacts substantially on the prognostic information given to women as well as their clinical management. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Anatomical subgroup analysis of the MERIDIAN cohort: ventriculomegaly.

OBJECTIVE: To assess the contribution of fetal magnetic resonance imaging (MRI) in fetuses of the MERIDIAN cohort diagnosed with ventriculomegaly (VM) as the only abnormal intracranial finding on antenatal ultrasound. METHODS: This was a subgroup analysis of the MERIDIAN study of fetuses with only VM diagnosed on ultrasound in women who had a subsequent MRI examination within 2 weeks and for whom outcome reference data were available. The diagnostic accuracy of ultrasound and MRI was reported in relation to the severity of VM. The difference in measurements of trigone size on the two imaging methods and the clinical impact of adding MRI to the diagnostic pathway were also studied. RESULTS: In 306 fetuses with VM, ultrasound failed to detect 31 additional brain abnormalities, having an overall diagnostic accuracy of 89.9% for ultrasound, whilst MRI correctly detected 27 of the additional brain abnormalities, having a diagnostic accuracy of 98.7% (P < 0.0001). There were other brain abnormalities in 14/244 fetuses with mild VM on ultrasound (diagnostic accuracy, 94.3%) and MRI correctly diagnosed 12 of these (diagnostic accuracy, 99.2%; P = 0.0005). There was a close agreement between the size of trigones measured on ultrasound and on MRI, with categorical differences in only 16% of cases, showing that MRI did not systematically overestimate or underestimate trigone size. Complete prognostic data were available in 295/306 fetuses and the prognosis category changed after MRI in 69/295 (23.4%) cases. The overall effect of MRI on clinical management was considered to be 'significant', 'major' or 'decisive' in 76/295 (25.8%) cases. CONCLUSION: Our data suggest that a woman carrying a fetus with VM as the only intracranial finding on ultrasound should be offered an adjuvant investigation by MRI for further evaluation. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Change in diagnostic confidence brought about by using in utero MRI for fetal structural brain pathology: analysis of the MERIDIAN cohort.

AIM: To measure possible change in diagnostic confidence by performing in utero magnetic resonance imaging (iuMRI) studies on fetuses with brain abnormalities recognised on ultrasonography (US). MATERIALS AND METHODS: The analyses are based on the primary cohort from the prospective MERIDIAN study, which consisted of 570 fetuses with brain abnormalities detected on US, with iuMRI performed within 2 weeks of US and complete outcome reference data. The cohort was recruited between July 2011 and August 2014, and written informed consent was obtained for all participants. They all had indicators of diagnostic confidence measured on US by fetal medicine experts and iuMRI by the reporting radiologists. Three assessments were carried out using the conventional uncorrected (C2-C1%) method, the conventional (C2-C1%) with the Omary correction, and the score-based weighted average method. RESULTS: All three assessments showed statistically significant (p<0·0001) positive effects indicating that iuMRI was potentially beneficial when included in the diagnostic pathway for prenatal structural brain anomalies (in terms of diagnostic confidence). CONCLUSION: These results strongly support the routine clinical use of iuMRI as an adjunct to US when assessing fetuses with structural brain abnormalities.

A pictorial review of imaging in paediatric stroke.

Stroke is recognised as an important disease in adults. Paediatric stroke is less understood, yet still an important cause of morbidity and mortality, with an incidence of 5 per 100 000 children and is one of the top 10 leading causes of death in children. In adults the vast majority of strokes are ischaemic, whereas in children haemorrhage makes up half the cases. The incidence of neonatal stroke is much higher, at up to 45 per 100 000 population; however, the underlying causes are less understood. This paper acts as a guide to the different causes of stroke with the key differences on imaging discussed.

Differentiation of Cardiac from Noncardiac Pleural Effusions in Cats using Second-Generation Quantitative and Point-of-Care NT-proBNP Measurements.

BACKGROUND: Pleural effusion is a common cause of dyspnea in cats. N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement, using a first-generation quantitative ELISA, in plasma and pleural fluid differentiates cardiac from noncardiac causes of pleural effusion. HYPOTHESIS/OBJECTIVES: To determine whether NT-proBNP measurements using second-generation quantitative ELISA and point-of-care (POC) tests in plasma and pleural fluid distinguish cardiac from noncardiac pleural effusions and how results compare to the first-generation ELISA. ANIMALS: Thirty-eight cats (US cohort) and 40 cats (UK cohort) presenting with cardiogenic or noncardiogenic pleural effusion. METHODS: Prospective cohort study. Twenty-one and 17 cats in the US cohort, and 22 and 18 cats in the UK cohort were classified as having cardiac or noncardiac pleural effusion, respectively. NT-proBNP concentrations in paired plasma and pleural fluid samples were measured using second-generation ELISA and POC assays. RESULTS: The second-generation ELISA differentiated cardiac from noncardiac pleural effusion with good diagnostic accuracy (plasma: sensitivity, 95.2%, specificity, 82.4%; pleural fluid: sensitivity, 100%, specificity, 76.5%). NT-proBNP concentrations were greater in pleural fluid (719 pmol/L (134-1500)) than plasma (678 pmol/L (61-1500), P = 0.003), resulting in different cut-off values depending on the sample type. The POC test had good sensitivity (95.2%) and specificity (87.5%) when using plasma samples. In pleural fluid samples, the POC test had good sensitivity (100%) but low specificity (64.7%). Diagnostic accuracy was similar between first- and second-generation ELISA assays. CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of NT-proBNP using a quantitative ELISA in plasma and pleural fluid or POC test in plasma, but not pleural fluid, distinguishes cardiac from noncardiac causes of pleural effusion in cats.

Assessment of mitral regurgitation in dogs: comparison of results of echocardiography with magnetic resonance imaging.

OBJECTIVES: Echocardiography is used routinely to assess mitral regurgitation severity, but echocardiographic measures of mitral regurgitation in dogs have not been compared with other quantitative methods. The study aim was to compare echocardiographic measures of mitral regurgitation with cardiac magnetic resonance imaging-derived mitral regurgitant fraction in small-breed dogs. METHODS: Dogs with myxomatous mitral valve disease scheduled for magnetic resonance imaging assessment of neurological disease were recruited. Correlations were tested between cardiac magnetic resonance imaging-derived mitral regurgitant fraction and the following echocardiographic measures: vena contracta/aortic diameter, transmitral E-wave velocity, amplitude of mitral prolapse/aortic diameter, diastolic left ventricular diameter:aortic diameter, left atrium:aortic diameter, mitral regurgitation jet area ratio and regurgitant fraction calculated using the proximal isovelocity surface area method. RESULTS: Measurement of cardiac magnetic resonance imaging-derived mitral regurgitant fraction was attempted in 21 dogs. Twelve consecutive, complete studies were obtained and 10 dogs were included in the final analysis: vena contracta/aortic diameter (r = 0 · 89, p = 0 · 001) and E-wave velocity (r = 0 · 86, p = 0 · 001) had the strongest correlations with cardiac magnetic resonance imaging-derived mitral regurgitant fraction. E velocity had superior repeatability and could be measured in all dogs. The presence of multiple jets precluded vena contracta/aortic diameter measurement in one dog. CLINICAL SIGNIFICANCE: Measurement of cardiac magnetic resonance imaging-derived mitral regurgitant fraction is feasible but technically demanding. The echocardiographic measures that correlated most closely with cardiac magnetic resonance imaging-derived mitral regurgitant fraction were vena contracta/aortic diameter and E-wave velocity.

Association of tricuspid annular plane systolic excursion with survival time in Boxer dogs with ventricular arrhythmias.

BACKGROUND: Tricuspid annular plane systolic excursion (TAPSE) is a useful estimate of right ventricular function in humans. Reference intervals for dogs have been generated, but the value of measuring TAPSE in other diseases, or investigating the association between TAPSE and outcome, is unknown. HYPOTHESIS: TAPSE is lower in Boxer dogs with ≥50 VPCs/24 h on Holter than in dogs with fewer ventricular ectopics, and lower TAPSE is associated with a shorter survival time. ANIMALS: Fifty Boxer dogs that presented for investigation of syncope or suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) at a veterinary teaching hospital (2004-2011). METHODS: Retrospective study. Clinical records, Holter, and echocardiographic data were reviewed. TAPSE was measured in a blinded manner on stored echocardiographic cine-loops using anatomic M-mode. Outcome information was obtained and death was classified as cardiac or noncardiac. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: TAPSE was lower in Boxers with ≥50 VPCs/24 h (13.9 ± 4.04 mm) than Boxers with <50 VPCs/24 h (16.8 ± 3.21 mm; P < .001). TAPSE <15.1 mm was associated with shorter cardiac survival time in all dogs (P = .004) and also in dogs without left ventricular dysfunction (P = .035). When controlling for other variables, including ventricular tachycardia on Holter and left ventricular systolic dysfunction, multivariable analysis showed that TAPSE remained an independent predictor of time to cardiac death (HR >4.09, 95%CI 1.15-16.9, P < .029). CONCLUSIONS AND CLINICAL IMPORTANCE: TAPSE offers prognostic value for Boxer dogs, including those with apparently normal systolic function and ≥50 VPCs/24 h on Holter analysis.

Circulating concentrations of a marker of type I collagen metabolism are associated with hypertrophic cardiomyopathy mutation status in ragdoll cats.

OBJECTIVES: Human carriers of hypertrophic cardiomyopathy associated sarcomeric mutations have abnormal collagen metabolism before overt left ventricular hypertrophy is detectable. This study investigated whether differences in collagen biomarkers were present in blood samples of ragdoll cats positive for the MYBPC3:R820W mutation compared with negative controls. MATERIALS AND METHODS: Cats were recruited for hypertrophic cardiomyopathy screening using echocardiography and genotyping. Circulating markers of collagen turnover (C-terminal telopeptide of type I collagen [CITP; type I collagen degradation] and N-terminal propeptide of type III procollagen [type III collagen synthesis]) and cardiac biomarkers (N-terminal B-type natriuretic peptide and cardiac troponin I) were measured. Correlation between concentrations of collagen biomarkers and echocardiographic variables was analysed, and collagen biomarker concentrations were compared between MYBPC3 mutation positive and negative cats, without left ventricular hypertrophy. RESULTS: Linear regression analyses showed that genotype was independently associated with CITP concentration. CITP was higher in mutation carriers (25 · 4 µg/L, interquartile range 16 · 0-29 · 2 µg/L) than non-carriers (14 · 6 µg/L, interquartile range 9 · 38-19 · 2 µg/L; P = 0 · 024). CLINICAL SIGNIFICANCE: Circulating CITP was higher in MYBPC3-positive ragdoll cats than negative controls and may indicate altered collagen metabolism. Further studies are necessary to determine whether alterations in circulating collagen biomarker concentration relate to an early stage of hypertrophic cardiomyopathy.

Retrospective evaluation of moderate-to-severe pulmonary hypertension in dogs naturally infected with Angiostrongylus vasorum.

OBJECTIVES: The outcome in dogs with pulmonary hypertension associated with natural Angiostrongylus vasorum infection is unclear. This study aimed to report long-term outcome of dogs with A. vasorum and pulmonary hypertension, and to evaluate factors associated with pulmonary hypertension development. It was hypothesised that dogs with pulmonary hypertension had a shorter survival time than dogs without pulmonary hypertension. METHODS: Retrospective review of clinical records of dogs diagnosed with A. vasorum. Dogs were classified as having or not having pulmonary hypertension based on clinical signs and imaging findings. Signalment, signs and outcome were recorded. DNA obtained from banked samples was genotyped for the PDE5a:E90K polymorphism, a possible factor in development of pulmonary hypertension. RESULTS: The proportion of dogs with moderate-to-severe pulmonary hypertension and A. vasorum infection in the study population was 14 · 6%. No difference in the population characteristics or PDE5a genotype was detected between dogs with and without pulmonary hypertension. Dogs with pulmonary hypertension had a significantly shorter survival time (P = 0 · 006) and a greater risk of death within 6 months of diagnosis (odds ratio 12 · 5, 95% confidence interval 2 · 1 to 74 · 9; P = 0 · 0053). CLINICAL SIGNIFICANCE: A. vasorum-associated pulmonary hypertension is an important problem in naturally infected dogs and has a negative effect upon survival.

Evaluation of red blood cell distribution width in cats with hypertrophic cardiomyopathy.

BACKGROUND: Red blood cell distribution width (RDW) is a measurement of variability in circulating erythrocytes size, and has recently been shown to correlate with prognosis in a variety of human diseases, including acute and chronic heart failure. OBJECTIVES: To determine if RDW differs between healthy controls, cats with hypertrophic cardiomyopathy (HCM) without congestive heart failure (CHF) and cats with HCM and CHF, and to evaluate whether RDW values at presentation can provide useful prognostic information in cats with HCM. ANIMALS: Retrospective single-centre study. Seventy-three cats diagnosed with HCM by echocardiography and 30 healthy controls presented to a veterinary teaching hospital between October 2006 and April 2013 were included. Physical examination, haematology and echocardiographic data obtained on one single visit were retrospectively reviewed and compared between three groups: controls, cats with HCM without CHF, and cats with HCM and CHF. Outcome data were obtained from clinical records or referring veterinarians. Univariable and multivariable survival analyses were performed. RESULTS: Red blood cell distribution width was significantly greater in cats with HCM and CHF compared with cats with HCM without CHF, and the controls. It was also significantly associated with cardiac mortality in univariable survival analysis, and this association remained significant in multivariable survival analysis after controlling for the effect of CHF, left atrial size, left ventricular systolic function, haematocrit and pro-thrombotic state. CONCLUSIONS: A higher RDW may be seen in cats with CHF and is an independent predictor of cardiac death in cats with HCM without concurrent non-cardiac-related illness.

Risk factors associated with sudden death vs. congestive heart failure or arterial thromboembolism in cats with hypertrophic cardiomyopathy.

OBJECTIVES: To evaluate risk factors associated with different types of cardiac death in cats with hypertrophic cardiomyopathy (HCM). ANIMALS: Two hundred fifty-five cats with HCM referred to a veterinary teaching hospital. METHODS: This is a retrospective study. Cats with HCM were identified that had either died within 2 years of diagnosis or were known to be alive 2 years after initial examination. Signalment, physical exam, electrocardiographic and echocardiographic data were analyzed separately for association with death due to congestive heart failure (CHF) vs. aortic thromboembolism (ATE) vs. sudden death. RESULTS: Within 2 years of follow-up, 23/255 (9.0%) cats had died with ATE, 44/255 (17.3%) cats had died with CHF and 12/255 (4.7%) cats had experienced a sudden death, with 141/255 (55.3%) cats still alive at the end of 2 years. Presence of CHF at presentation and reduced left ventricular fractional shortening (FS%) were independently associated with a CHF death within 2 years of diagnosis. Presence of ATE and reduced left atrial fractional shortening (LA-FS%) were independently associated with dying with ATE within 2 years. No multivariable models were generated for risks of dying a sudden death owing to the low event rate, but syncope at presentation and arrhythmias on auscultation were associated with sudden death on univariable analysis. CONCLUSIONS: Asymptomatic cats have a reduced risk of all three types of death. Reduced FS% and a history of CHF independently predict CHF death, and reduced LA-FS% and history of ATE independently predict ATE death. Sudden death is less commonly reported but is associated with syncope.