Automated echocardiographic left ventricular dimension assessment in dogs using artificial intelligence: Development and validation.

BACKGROUND: Artificial intelligence (AI) could improve accuracy and reproducibility of echocardiographic measurements in dogs. HYPOTHESIS: A neural network can be trained to measure echocardiographic left ventricular (LV) linear dimensions in dogs. ANIMALS: Training dataset: 1398 frames from 461 canine echocardiograms from a single specialist center. VALIDATION: 50 additional echocardiograms from the same center. METHODS: Training dataset: a right parasternal 4-chamber long axis frame from each study, labeled by 1 of 18 echocardiographers, marking anterior and posterior points of the septum and free wall. VALIDATION DATASET: End-diastolic and end-systolic frames from 50 studies, annotated twice (blindly) by 13 experts, producing 26 measurements of each site from each frame. The neural network also made these measurements. We quantified its accuracy as the deviation from the expert consensus, using the individual-expert deviation from consensus as context for acceptable variation. The deviation of the AI measurement away from the expert consensus was assessed on each individual frame and compared with the root-mean-square-variation of the individual expert opinions away from that consensus. RESULTS: For the septum in end-diastole, individual expert opinions deviated by 0.12 cm from the consensus, while the AI deviated by 0.11 cm (P = .61). For LVD, the corresponding values were 0.20 cm for experts and 0.13 cm for AI (P = .65); for the free wall, experts 0.20 cm, AI 0.13 cm (P < .01). In end-systole, there were no differences between individual expert and AI performances. CONCLUSIONS AND CLINICAL IMPORTANCE: An artificial intelligence network can be trained to adequately measure linear LV dimensions, with performance indistinguishable from that of experts.

A multicenter, retrospective study of cardiac disease in Borzoi dogs.

Borzoi are large, relatively uncommon sighthounds anecdotally reported to suffer from sudden death. This multicenter retrospective cohort study aimed to describe the sample of Borzoi presenting to veterinary cardiologists for evaluation, with records searched from 14 centers across a study period of up to 20 years. The study sample was comprised of 152 client-owned Borzoi, with dogs most commonly presenting for pre-breed screening in 87/152 (52%), followed by evaluation of an arrhythmia in 28/152 (18%). Of the 131/152 (86%) dogs that had an echocardiogram performed, 85/131 (65%) were structurally normal, with 40/85 (47%) structurally normal dogs having trace or mild atrioventricular valve regurgitation. Tricuspid valve dysplasia was the most commonly diagnosed congenital cardiac disease (n = 6). Myxomatous mitral valve disease (n = 12) and dilated cardiomyopathy (n = 13) were diagnosed at similar frequencies, though 92% of valve disease cases were mild. Only 48/152 (32%) Borzoi had a diagnostic electrocardiogram (ECG) and/or a Holter monitor for arrhythmia screening. Despite this, ventricular arrhythmias were identified during the entirety of the available cardiac evaluation including diagnostic ECG, contemporaneous ECG monitoring during the echocardiogram, and/or Holter monitor in 25/131 (19%) dogs in which an echocardiographic diagnosis was available. Of these 25 Borzoi, 76% had minimal or no structural cardiac disease identified, and five had a family history of sudden death. A sudden death outcome was reported in 3/55 (5%) Borzoi with long-term outcome data available. In conclusion, Borzoi commonly have trace or mild atrioventricular valve insufficiencies, and may develop ventricular arrhythmias and dilated cardiomyopathy.

Retrospective evaluation of hypertrophic cardiomyopathy in 68 dogs.

BACKGROUND: There is a lack of clinical data on hypertrophic cardiomyopathy (HCM) in dogs. HYPOTHESIS/OBJECTIVES: To investigate signalment, clinical signs, diagnostic findings, and survival in dogs with HCM. ANIMALS: Sixty-eight client-owned dogs. METHODS: Retrospective multicenter study. Medical records were searched between 2003 and 2015. The diagnosis of left ventricular (LV) hypertrophy was made by echocardiographic examination. RESULTS: Three hundred and forty-five dogs with LV hypertrophy were identified, of which 277 were excluded. The remaining 68 dogs were 0.3 to 14 years old and predominantly <10 kg (85%), and without a sex predilection. Twenty-four % were Shih Tzu and 24% terrier breeds. Most (80%) had a systolic heart murmur. Owner-determined exercise intolerance (37%) and syncope (18%) were most commonly reported signs. The majority (84%) of dogs had symmetrical LV hypertrophy, whereas asymmetrical septal and LV free wall hypertrophy was observed in 9% and 6% of dogs, respectively. Isolated basal interventricular septal hypertrophy was not observed. Commonly recorded were systolic anterior motion of the mitral valve (60%) and LV diastolic dysfunction (89% of dogs where diastolic function was evaluated). Six dogs died unexpectedly, and 3 developed congestive heart failure. Known survival times were between 1 day and 114 months after diagnosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Hypertrophic cardiomyopathy in dogs should be considered as a differential diagnosis if LV hypertrophy is identified. Small breed dogs are overrepresented, and it is uncommon for dogs with HCM to develop CHF although sudden death can occur.

Comparison of a Deep Learning Algorithm vs. Humans for Vertebral Heart Scale Measurements in Cats and Dogs Shows a High Degree of Agreement Among Readers.

Heart disease is a leading cause of death among cats and dogs. Vertebral heart scale (VHS) is one tool to quantify radiographic cardiac enlargement and to predict the occurrence of congestive heart failure. The aim of this study was to evaluate the performance of artificial intelligence (AI) performing VHS measurements when compared with two board-certified specialists. Ground truth consisted of the average of constituent VHS measurements performed by board-certified specialists. Thirty canine and 30 feline thoracic lateral radiographs were evaluated by each operator, using two different methods for determination of the cardiac short axis on dogs' radiographs: the original approach published by Buchanan and the modified approach proposed by the EPIC trial authors, and only Buchanan's method for cats' radiographs. Overall, the VHS calculated by the AI, radiologist, and cardiologist had a high degree of agreement in both canine and feline patients (intraclass correlation coefficient (ICC) = 0.998). In canine patients, when comparing methods used to calculate VHS by specialists, there was also a high degree of agreement (ICC = 0.999). When evaluating specifically the results of the AI VHS vs. the two specialists' readings, the agreement was excellent for both canine (ICC = 0.998) and feline radiographs (ICC = 0.998). Performance of AI trained to locate VHS reference points agreed with manual calculation by specialists in both cats and dogs. Such a computer-aided technique might be an important asset for veterinarians in general practice to limit interobserver variability and obtain more comparable VHS reading over time.

Evaluation of hemostasis in hyperthyroid cats.

BACKGROUND: Hyperthyroid cats might have a predisposition to arterial thrombus formation. The mechanism for thrombogenesis currently is unknown but could be associated with systemic hypercoagulability as seen in hyperthyroid humans. OBJECTIVE: Our purpose was to evaluate markers of hemostasis in hyperthyroid cats compared to healthy cats, and in hyperthyroid cats before and after radioactive iodine treatment (RIT). ANIMALS: Twenty-five cats with hyperthyroidism and 13 healthy euthyroid cats >8 years of age. METHODS: Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, antithrombin (AT), D-dimers, thrombin-antithrombin complexes (TAT), von Willebrand Factor antigen (vWF : Ag), and activity of factors VIII and IX were measured. An echocardiogram was performed in all cats. Hemostatic markers and echocardiogram were evaluated again 6 to 9 months after successful RIT in 7 cats. RESULTS: Hyperthyroid cats had higher fibrinogen concentration (P < .0001), AT activity (P < .0001), and vWF : Ag concentration (P = .01) than healthy control cats with all results decreasing significantly post-RIT. Hyperthyroid cats were not more likely to be in a hypercoaguable state than euthyroid cats (P = .08). Serum T4 concentration was not a predictor of a hypercoagulable state (P = .53). CONCLUSIONS AND CLINICAL IMPORTANCE: Hyperthyroid cats have evidence of altered hemostasis that does not appear to be solely attributable to cardiac abnormalities, but no evidence of a hypercoagulable state. Findings suggest altered hemostasis resolves after RIT. Hyperthyroid cats could have endothelial dysfunction as indicated by increased vWF : Ag which could potentiate thrombogenesis.

Clinical characteristics of cats referred for evaluation of subclinical cardiac murmurs.

OBJECTIVES: The aim of this study was to define the clinical characteristics of cats referred for evaluation of subclinical cardiac murmurs, and, secondarily, to identify predictors of echocardiographic identification of cardiac disease. METHODS: One hundred and sixty-three apparently healthy cats with subclinical murmurs were retrospectively enrolled. Medical records of cats older than 1 year of age referred for the evaluation of subclinical murmurs were reviewed. Cats were considered healthy if clinical signs of systemic disease or cardiac disease were not reported and cats were not receiving cardiac medications. Logistic regression was used to identify clinical variables that predict echocardiographic identification of cardiac disease. RESULTS: One hundred and eight cats (66.3%) had echocardiographic evidence of cardiac disease with hypertrophic cardiomyopathy being the most common (80.5%). Left atrial enlargement was uncommon; in 90% of cats with echocardiographically identified cardiac disease, the left atrial aortic ratio from two-dimensional echocardiography was <1.51. Cats with cardiac disease were more likely to be male (P = 0.016), weigh more (P <0.01) and have a murmur of intensity ⩾3/6 (P = 0.019) than cats without cardiac disease. Murmur intensity ⩾grade 3/6 (P = 0.01) and male sex (P = 0.01) were independent predictors of echocardiographic evidence of cardiac disease in multivariable analysis. CONCLUSIONS AND RELEVANCE: The majority of cats referred for evaluation of subclinical cardiac murmurs have cardiac disease. Based on left atrial dimensions, cardiac disease is generally mild. Male sex and a loud cardiac murmur are associated with the identification of cardiac disease.

Dose-Escalation and Pharmacokinetic Study Following a Single Dose of Oxaliplatin in Cancer-Bearing Dogs.

Oxaliplatin is more potent than cisplatin, lacks cross-resistance to other platinum agents, and has a favorable toxicity profile. This study's objective was to define the maximally tolerated dose and the dose-limiting toxicity (DLT) of oxaliplatin in cancer-bearing dogs. This was a prospective, single-patient-cohort, dose-escalation study of oxaliplatin in client-owned dogs with confirmed, spontaneous malignancy. A single infusion was administered; the starting dose was 50 mg/m2, with 10 mg/m2 escalation-increments if no DLT was documented, up to a maximum dose of 140 mg/m2. Plasma total platinum was measured at multiple timepoints and patients were monitored weekly. Ten dogs were enrolled in single-patient-cohort treatment levels up to the maximum level of 140 mg/m2. There were no DLTs, and the maximally tolerated dose was not determined. The area under the curve0-7 days for 100-140 mg/m2 ranged from 77,850 to 82,860 ng/mL × hr; the area under the curve0-4 hr for 50-140 mg/m2 was linear with dose (r2 = 0.639, P = .0055). The data suggest a single infusion of oxaliplatin is well tolerated in cancer-bearing dogs up to 140 mg/m2. There was good correlation between exposure and dose, while achieving plasma levels similar to therapeutic levels documented in humans.

ACVIM consensus statement guidelines for the classification, diagnosis, and management of cardiomyopathies in cats.

Cardiomyopathies are a heterogeneous group of myocardial disorders of mostly unknown etiology, and they occur commonly in cats. In some cats, they are well-tolerated and are associated with normal life expectancy, but in other cats they can result in congestive heart failure, arterial thromboembolism or sudden death. Cardiomyopathy classification in cats can be challenging, and in this consensus statement we outline a classification system based on cardiac structure and function (phenotype). We also introduce a staging system for cardiomyopathy that includes subdivision of cats with subclinical cardiomyopathy into those at low risk of life-threatening complications and those at higher risk. Based on the available literature, we offer recommendations for the approach to diagnosis and staging of cardiomyopathies, as well as for management at each stage.

Temporal changes in clinical and radiographic variables in dogs with preclinical myxomatous mitral valve disease: The EPIC study.

BACKGROUND: The Evaluation of pimobendan in dogs with cardiomegaly caused by preclinical myxomatous mitral valve disease (EPIC) study monitored dogs with myxomatous mitral valve disease (MMVD) as they developed congestive heart failure (CHF). OBJECTIVES: To describe the changes in clinical and radiographic variables occurring as dogs with MMVD and cardiomegaly develop CHF, compared to similar dogs that do not develop CHF. ANIMALS: One hundred and thirty-five, and 73 dogs that did or did not develop CHF, respectively. MATERIALS AND METHODS: The following variables were evaluated in 2 groups of dogs (dogs that did or did not develop CHF): Heart rate (HR), clinic respiratory rate (RR), home-measured resting respiratory rate (RRR), rectal temperature (RT), body weight (BW), and vertebral heart sum (VHS). Absolute value and rate of change of each variable were calculated for each day a dog was in study. Daily means were calculated and plotted against time. The onset of CHF or last visit before leaving the study were set as reference time points. RESULTS: The most extreme values and rate of change occurred in variables immediately before onset of CHF. Vertebral heart sum increased earliest. Heart rate, RR, and RRR also increased. Rectal temperature and BW decreased. Increases in RR and RRR were most extreme and occurred immediately before CHF. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with MMVD and cardiomegaly experience increases in HR, RR, RRR, and VHS, and decreases in BW and RT as they develop CHF. The variables with highest absolute change and rate of change were RR and RRR. These findings reinforce the value of RR and RRR as indicators of impending or incipient CHF.

Echocardiographic and electrocardiographic evaluation of North American Irish Wolfhounds.

BACKGROUND: Cardiac disease is an important cause of morbidity and mortality in Irish Wolfhounds (IWs), but its prevalence and clinical characteristics in North American IWs are incompletely described. HYPOTHESIS/OBJECTIVES: That atrial fibrillation (AF) is a diagnostic marker of echocardiographic abnormalities, and that clinical characteristics predict development of IW cardiomyopathy (IWCM). To define the prevalence of arrhythmias and echocardiographic abnormalities in North American IWs. ANIMALS: Six hundred and forty-five adult IWs presented for screening examinations intended to identify familial cardiac disease. METHODS: In this retrospective cohort study, reference intervals defined based on echocardiographic data from IW classified as normal, were used to define the prevalence of structural and functional abnormalities. A logistic model was developed to identify clinical findings that predict future development of IWCM. RESULTS: The prevalence of AF was 8.9% (95% confidence interval [CI], 6.6-11.2) of which 55.5% had echocardiographic abnormalities. IWCM defined by left atrial enlargement, left ventricular dilatation, and systolic dysfunction had a prevalence of 1.8% (0.72-2.8). Positive and negative likelihood ratios for AF in the identification of IWCM were, respectively, 10.8 (7.29-16) and 0.2 (0.06-0.69). Multivariable logistic regression identified AF (odds ratio [OR]; 10.6, 95% CI, 2.67-42.3) and male sex (OR; 3.8, 95% CI, 1.02-14) as predictors of future development of IWCM. CONCLUSIONS AND CLINICAL IMPORTANCE: Atrial fibrillation is common in North American IW. It occurs in association with structural cardiac disease but also in its absence. Irish Wolfhounds cardiomyopathy is characterized by chamber enlargement but minimally decreased ejection phase indices of myocardial function. Atrial fibrillation is a risk factor for future development of IWCM.

ACVIM consensus statement guidelines for the diagnosis, classification, treatment, and monitoring of pulmonary hypertension in dogs.

Pulmonary hypertension (PH), defined by increased pressure within the pulmonary vasculature, is a hemodynamic and pathophysiologic state present in a wide variety of cardiovascular, respiratory, and systemic diseases. The purpose of this consensus statement is to provide a multidisciplinary approach to guidelines for the diagnosis, classification, treatment, and monitoring of PH in dogs. Comprehensive evaluation including consideration of signalment, clinical signs, echocardiographic parameters, and results of other diagnostic tests supports the diagnosis of PH and allows identification of associated underlying conditions. Dogs with PH can be classified into the following 6 groups: group 1, pulmonary arterial hypertension; group 2, left heart disease; group 3, respiratory disease/hypoxia; group 4, pulmonary emboli/pulmonary thrombi/pulmonary thromboemboli; group 5, parasitic disease (Dirofilaria and Angiostrongylus); and group 6, disorders that are multifactorial or with unclear mechanisms. The approach to treatment of PH focuses on strategies to decrease the risk of progression, complications, or both, recommendations to target underlying diseases or factors contributing to PH, and PH-specific treatments. Dogs with PH should be monitored for improvement, static condition, or progression, and any identified underlying disorder should be addressed and monitored simultaneously.

Long-term incidence and risk of noncardiovascular and all-cause mortality in apparently healthy cats and cats with preclinical hypertrophic cardiomyopathy.

BACKGROUND: Epidemiologic knowledge regarding noncardiovascular and all-cause mortality in apparently healthy cats (AH) and cats with preclinical hypertrophic cardiomyopathy (pHCM) is limited, hindering development of evidence-based healthcare guidelines. OBJECTIVES: To characterize/compare incidence rates, risk, and survival associated with noncardiovascular and all-cause mortality in AH and pHCM cats. ANIMALS: A total of 1730 client-owned cats (722 AH, 1008 pHCM) from 21 countries. METHODS: Retrospective, multicenter, longitudinal, cohort study. Long-term health data were extracted by medical record review and owner/referring veterinarian interviews. RESULTS: Noncardiovascular death occurred in 534 (30.9%) of 1730 cats observed up to 15.2 years. Proportion of noncardiovascular death did not differ significantly between cats that at study enrollment were AH or had pHCM (P = .48). Cancer, chronic kidney disease, and conditions characterized by chronic weight-loss-vomiting-diarrhea-anorexia were the most frequently recorded noncardiovascular causes of death. Incidence rates/risk of noncardiac death increased with age in AH and pHCM. All-cause death proportions were greater in pHCM than AH (65% versus 40%, respectively; P < .001) because of higher cardiovascular mortality in pHCM cats. Comparing AH with pHCM, median survival (study entry to noncardiovascular death) did not differ (AH, 9.8 years; pHCM, 8.6 years; P = .10), but all-cause survival was significantly shorter in pHCM (P = .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: All-cause mortality was significantly greater in pHCM cats due to disease burden contributed by increased cardiovascular death superimposed upon noncardiovascular death.

Duration of ß-adrenoceptor blockade associated with once-daily oral administration of atenolol in healthy dogs.

OBJECTIVE To test the hypothesis that once-daily oral administration of atenolol would attenuate the heart rate response to isoproterenol for 24 hours. ANIMALS 20 healthy dogs. PROCEDURES A double-blind randomized placebo-controlled crossover study was conducted. Dogs were assigned to receive atenolol (1 mg/kg, PO, q 24 h) or a placebo for 5 to 7 days. After a washout period of 7 days, dogs then received the other treatment. Heart rate at rest (HRr) and heart rate induced by administration of isoproterenol (HRi) as a constant rate infusion (0.2 µg/kg/min for 5 to 7 minutes) were obtained by use of ECG 0, 0.25, 3, 6, 12, 18, and 24 hours after administration of the final dose of atenolol or the placebo. A mixed-model ANOVA was used to evaluate effects of treatment, time after drug or placebo administration, treatment-by-time interaction, period, and sequence on HRr and HRi. RESULTS Effects of sequence or period were not detected. There was a significant effect of treatment and the treatment-by-time interaction on HRi. Atenolol significantly attenuated HRi for 24 hours but did so maximally at 3 hours (least squares mean ± SE, 146 ± 5 beats/min and 208 ± 5 beats/min for atenolol and placebo, respectively). The effect at 24 hours was small (193 ± 5 beats/min and 206 ± 5 beats/min for atenolol and placebo, respectively). Atenolol had a small but significant effect on HRr. CONCLUSIONS AND CLINICAL RELEVANCE This study of healthy dogs receiving atenolol supported a recommendation for a dosing interval < 24 hours.

Dilated cardiomyopathy with endocardial fibroelastosis in a juvenile Pallas cat.

Dilated cardiomyopathy (DCM) is a myocardial disease characterized by ventricular chamber dilation associated with systolic myocardial dysfunction in the absence of other cardiac lesions. DCM occasionally develops in conjunction with proliferation of fibroelastic fibers in the endocardium, producing endocardial fibroelastosis (EFE). Although early reports describe EFE as a primary disease, evidence now suggests that EFE may develop as a response to myocardial dysfunction. Echocardiographic evaluation of a 4-wk-old Pallas cat ( Otocolobus manul) with respiratory distress revealed enlargement of both atria, enlarged end-systolic left ventricular dimension, and left ventricular dilation. DCM was diagnosed, and the cat was euthanized, given the poor prognosis. Postmortem examination revealed pericardial effusion and biventricular and biatrial enlargement. The interventricular septum and free walls of ventricles were thin. Histologically, the endocardium of the left and right ventricles was diffusely thickened; Verhoeff-Van Gieson staining of the left ventricular endocardium revealed a moderate amount of endocardial accumulation of elastin and collagen. These fibers were more prominent in papillary muscles and around coronary blood vessels. Based on these findings, we diagnosed DCM with EFE. Cardiac diseases are rarely diagnosed in wild felids.

Infant Feeding Practices, Workplace Breastfeeding/Lactation Practices, and Perception of Unit/Service Support Among Primiparous Active Duty Servicewomen.

INTRODUCTION: Successful breastfeeding provides multiple health benefits to Servicewomen and their infants and has positive indirect benefits to the military. Workplace lactation support influences breastfeeding continuation after a Servicewoman's return to work. MATERIALS AND METHODS: This study evaluated the breastfeeding practices and workplace breastfeeding support among primiparous women serving in the U.S. Army. The study was a subanalysis of a non-blinded randomized controlled trial designed to determine the effect of postpartum appointment timing (either 2-3 or 6-8 weeks after delivery) on breastfeeding rates 6 months post-delivery. Subanalysis results were obtained through a telephonic follow-up survey 5-6 months after delivery; Servicewomen were queried to assess their breastfeeding/lactation practices and perception of unit and service support. RESULTS: Eighty of the 97 (82.5%) enrolled Servicewomen participated in the survey. Among respondents, 43.8% were still breastfeeding and 93.6% of those indicated an intent to breastfeed for a duration of 6 months or longer. Among respondents who provided feedback on their workplace, unit, and Army support for breastfeeding/lactation, only 13% reported they had access to a private room, sink, and refrigerator; 53% of respondents felt "mostly" or "very" supported by their assigned unit and 50% felt "mostly" or "very" supported by the Army. CONCLUSION: While almost half of the respondents were still breastfeeding and planned to continue 5-6 months postpartum and the majority of respondents felt "mostly" or "very" supported in their breastfeeding by their unit and the Army, comprehensive physical support for lactation in the workplace was inconsistent. This study provides feedback to inform ongoing implementation of the existing Army breastfeeding support directive.

Effect of Follow-Up Intervals on Breastfeeding Rates 5-6 Months Postpartum: A Randomized Controlled Trial.

OBJECTIVE: To compare the effect of early versus traditional postpartum follow-up intervals on breastfeeding continuation rates 6 months postpartum. METHODS: This randomized controlled trial enrolled primiparous women planning to breastfeed to a postpartum appointment either 2-3 weeks or 6-8 weeks after delivery. The primary outcome was the breastfeeding rate in each group 5-6 months after delivery. The study was powered to detect a 50% difference between groups assuming a 34% rate of breastfeeding at 6 months. Participants were contacted by phone 5-6 months after delivery to assess outcomes. RESULTS: From March 2014 to July 2016, 649 women were screened and 344 enrolled as follows: 172 to 2-3 week and 172 to 6-8 week follow-up. Demographic, delivery, and support characteristics were similar between groups; however, average infant birth weight and the distribution of gestational ages at the time of delivery were different between groups (p < 0.05). Participants in the 2-3 week group had a breastfeeding rate of 57.7% 6 months following delivery and participants in the 6-8 week group had a rate of 59.3%. Early follow-up was associated with a relative risk of 0.97 (95% CI 0.79-1.19, p = 0.80) and an adjusted relative risk of 1.45 (95% CI 0.71-2.95, p = 0.31), when adjusted for confounding variables, for breastfeeding continuation at 5-6 months. CONCLUSIONS: Breastfeeding rates at 5-6 months postpartum were comparable between both groups; early follow-up was not associated with an increased rate of breastfeeding. At 6 months postpartum, the breastfeeding rate in both groups approximated the Surgeon General's Healthy People 2020 goal of 60.6%. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (Identifier NCT02221895).

Comparison of the mitral valve morphologies of Cavalier King Charles Spaniels and dogs of other breeds using 3D transthoracic echocardiography.

BACKGROUND: Myxomatous mitral valve disease (MMVD) is more prevalent in Cavalier King Charles Spaniels (CKCSs) compared to dogs of other breeds at a given age. Abnormal valvular stress is thought to contribute to the development and progression of MMVD, and a relationship exists between mitral valve (MV) morphology and stress acting on the valve. OBJECTIVES: To determine whether the MV morphology of healthy adult CKCSs differs from the morphology of healthy adult dogs of other breeds determined by RT-3DTTE. ANIMALS: Thirty-five healthy CKCSs and 41 healthy dogs of other breeds. METHODS: Prospective cross-sectional study. Dogs underwent physical examination, conventional echocardiography, and RT-3DTTE. RT-3DTTE datasets were analyzed using dedicated software for MV morphologic analysis. Morphologic variables were compared between CKCSs and dogs of other breeds. RESULTS: The MV of healthy CKCSs had a smaller annulus height (0.46 ± 0.11 vs. 0.56 ± 0.17; P = .0021), tenting height (0.26 ± 0.12 vs. 0.42 ± 0.18; P < .001), tenting area (0.42 ± 0.15 vs. 0.79 ± 0.34; P < .001), normalized tenting volume (0.09 [0.05-0.13] vs. 0.14 [0.10-0.20]; P < .001), and normalized area of the posterior leaflet (0.57 ± 0.15 vs. 0.66 ± 0.18; P = .016) compared to healthy dogs of other breeds; this results in CKCSs having a flatter MV with reduced tenting, compared to the MV of other breeds. CONCLUSIONS AND CLINICAL IMPORTANCE: These morphologic features could confer a mechanical disadvantage and play a role in the predisposition of CKCSs to the early development of MMVD.

International collaborative study to assess cardiovascular risk and evaluate long-term health in cats with preclinical hypertrophic cardiomyopathy and apparently healthy cats: The REVEAL Study.

BACKGROUND: Hypertrophic cardiomyopathy is the most prevalent heart disorder in cats and principal cause of cardiovascular morbidity and mortality. Yet, the impact of preclinical disease is unresolved. HYPOTHESIS/OBJECTIVES: Observational study to characterize cardiovascular morbidity and survival in cats with preclinical nonobstructive (HCM) and obstructive (HOCM) hypertrophic cardiomyopathy and in apparently healthy cats (AH). ANIMALS: One thousand seven hundred and thirty client-owned cats (430 preclinical HCM; 578 preclinical HOCM; 722 AH). METHODS: Retrospective multicenter, longitudinal, cohort study. Cats from 21 countries were followed through medical record review and owner or referring veterinarian interviews. Data were analyzed to compare long-term outcomes, incidence, and risk for congestive heart failure (CHF), arterial thromboembolism (ATE), and cardiovascular death. RESULTS: During the study period, CHF, ATE, or both occurred in 30.5% and cardiovascular death in 27.9% of 1008 HCM/HOCM cats. Risk assessed at 1, 5, and 10 years after study entry was 7.0%/3.5%, 19.9%/9.7%, and 23.9%/11.3% for CHF/ATE, and 6.7%, 22.8%, and 28.3% for cardiovascular death, respectively. There were no statistically significant differences between HOCM compared with HCM for cardiovascular morbidity or mortality, time from diagnosis to development of morbidity, or cardiovascular survival. Cats that developed cardiovascular morbidity had short survival (mean ± standard deviation, 1.3 ± 1.7 years). Overall, prolonged longevity was recorded in a minority of preclinical HCM/HOCM cats with 10% reaching 9-15 years. CONCLUSIONS AND CLINICAL IMPORTANCE: Preclinical HCM/HOCM is a global health problem of cats that carries substantial risk for CHF, ATE, and cardiovascular death. This finding underscores the need to identify therapies and monitoring strategies that decrease morbidity and mortality.

The pregnancy "super-utilizer": how does a high-risk depression screen affect medical utilization?

OBJECTIVE: Our objective was to determine whether a score of >11 on the Edinburgh postnatal depression scale (EPDS) at the initial prenatal visit was associated with an increased use of acute medical visits when compared to pregnant women with an initial EPDS score of ≤11. METHODS: This was a retrospective cohort study comparing the utilization of acute medical care during pregnancy and the first eight weeks after delivery amongst 200 women with an EPDS score >11 at their initial prenatal visit compared with 200 women with an EPDS score ≤11. "Super-utilization" was defined as ≥4 acute or unscheduled medical visits during pregnancy and the first eight weeks after delivery (90th percentile). Logistic regression was used to control for confounders. RESULTS: Women with an initial EPDS score >11 were significantly more likely to engage in super-utilization of acute medical care compared with those women scoring ≤11 (adjusted odds ratio [aOR], 2.12; 95% confidence interval [CI], 1.53-3.90). CONCLUSIONS: Pregnant women scoring >11 on the EPDS at their initial prenatal visit are more likely to super-utilize acute medical care in the perinatal period. This subset of patients at-risk for increased utilization can be identified early during prenatal care. Interventions to better meet the medical and psychosocial needs of these women warrant future research.

Class II phosphoinositide 3-kinase C2ß regulates a novel signaling pathway involved in breast cancer progression.

It is now well established that the enzymes phosphoinositide 3-kinases (PI3Ks) have a key role in the development and progression of many cancer types and indeed PI3Ks inhibitors are currently being tested in clinical trials. Although eight distinct PI3K isoforms exist, grouped into three classes, most of the evidence currently available are focused on one specific isoform with very little known about the potential role of the other members of this family in cancer. Here we demonstrate that the class II enzyme PI3K-C2ß is overexpressed in several human breast cancer cell lines and in human breast cancer specimens. Our data indicate that PI3K-C2ß regulates breast cancer cell growth in vitro and in vivo and that PI3K-C2ß expression in breast tissues is correlated with the proliferative status of the tumor. Specifically we show that downregulation of PI3K-C2ß in breast cancer cell lines reduces colony formation, induces cell cycle arrest and inhibits tumor growth, in particular in an estrogen-dependent in vivo xenograft. Investigation of the mechanism of the PI3K-C2ß-dependent regulation of cell cycle progression and cell growth revealed that PI3K-C2ß regulates cyclin B1 protein levels through modulation of microRNA miR-449a levels. Our data further demonstrate that downregulation of PI3K-C2ß inhibits breast cancer cell invasion in vitro and breast cancer metastasis in vivo. Consistent with this, PI3K-C2ß is highly expressed in lymph-nodes metastases compared to matching primary tumors. These data demonstrate that PI3K-C2ß plays a pivotal role in breast cancer progression and in metastasis development. Our data indicate that PI3K-C2ß may represent a key molecular switch that regulates a rate-limiting step in breast tumor progression and therefore it may be targeted to limit breast cancer spread.