Permanent stoma rates after anterior resection for rectal cancer: risk prediction scoring using preoperative variables.

BACKGROUND: A permanent stoma after anterior resection for rectal cancer is common. Preoperative counselling could be improved by providing individualized accurate prediction modelling. METHODS: Patients who underwent anterior resection between 2007 and 2015 were identified from the Swedish Colorectal Cancer Registry. National Patient Registry data were added to determine presence of a stoma 2 years after surgery. A training set based on the years 2007-2013 was employed in an ensemble of prediction models. Judged by the area under the receiving operating characteristic curve (AUROC), data from the years 2014-2015 were used to evaluate the predictive ability of all models. The best performing model was subsequently implemented in typical clinical scenarios and in an online calculator to predict the permanent stoma risk. RESULTS: Patients in the training set (n = 3512) and the test set (n = 1136) had similar permanent stoma rates (13.6 and 15.2 per cent). The logistic regression model with a forward/backward procedure was the most parsimonious among several similarly performing models (AUROC 0.67, 95 per cent c.i. 0.63 to 0.72). Key predictors included co-morbidity, local tumour category, presence of metastasis, neoadjuvant therapy, defunctioning stoma use, tumour height, and hospital volume; the interaction between age and metastasis was also predictive. CONCLUSION: Using routinely available preoperative data, the stoma outcome at 2 years after anterior resection for rectal cancer can be predicted fairly accurately.

Usually, the goal of rectal cancer surgery is to remove the tumour and construct a bowel join. Sometimes, it is necessary to construct a stoma, which may become permanent. Swedish registry data were used to develop and test a statistical model to forecast the risk of a stoma 2 years after surgery. In addition, an online calculator was developed. The model performed reasonably well, and can be used to inform the patient and surgeon before surgery of the risk of a permanent stoma.

Veterinary echocardiographers' preferences for left atrial size assessment in cats: the BENEFIT project.

INTRODUCTION/OBJECTIVES: Veterinary echocardiographers' preferences for left atrial (LA) size assessment in cats have not been systematically investigated. The primary aim of this prospective exploratory study was to investigate echocardiographers' preferences concerning LA size assessment in cats. A secondary aim was to investigate echocardiographers' preferences for assessing LA size in subgroups based on geographic, demographic, and professional profiles. ANIMALS, MATERIALS, AND METHODS: An online survey instrument was designed, verified, and distributed globally to veterinary echocardiographers. RESULTS: A total of 655 veterinary echocardiographers from six continents and 54 countries, working in specialty practice (56%) and in general practice (38%), provided data. Linear two-dimensional (2D) technique was favored by most echocardiographers (n = 612) for LA size assessment. Most commonly, respondents combined linear 2D with subjective assessment (n = 227), while 209 used linear 2D-based methods alone. Most echocardiographers using linear 2D-based methods preferred the right parasternal short-axis view and to index the LA to the aorta (Ao). Approximately 10% of the respondents obtained LA dimensions from a right parasternal long-axis four-chamber view. Approximately one-third of echocardiographers that made linear measurements from 2D echocardiograms shared the same preferences regarding cat position, acquisition view, indexing method and time point identification for the LA measurement. The responses were comparably homogeneous across geographic location, level of training, years performing echocardiography, and type of practice. DISCUSSION/CONCLUSION: Most veterinary echocardiographers assessed LA size in cats using linear 2D echocardiography from a right parasternal short-axis view, and indexed LA to Ao. Respondents' preferences were similar over geographic, demographic, and professional backgrounds.

Veterinary echocardiographers' preferences for left atrial size assessment in dogs: the BENEFIT project.

INTRODUCTION/OBJECTIVES: Veterinary echocardiographers' preferences for left atrial (LA) size assessment in dogs have never been systematically investigated. The primary aim of this international survey study was to investigate echocardiographers' preferences for LA size assessment in dogs. The secondary aim was to investigate echocardiographers' preferences for assessing LA size in subgroups based on geographic, demographic, and professional profiles. ANIMALS, MATERIALS, AND METHODS: An online survey instrument was designed, verified, and distributed globally to the veterinary echocardiographers. RESULTS: A total of 670 echocardiographers from 54 countries on six continents completed the survey. Most echocardiographers (n = 621) used linear two-dimensional (2D)-based methods to assess LA size, 379 used subjective assessment, and 151 used M-mode-based methods. Most commonly, echocardiographers combined linear 2D-based methods with subjective assessment (n = 222), whereas 191 used linear 2D-based methods alone. Most echocardiographers (n = 436) using linear 2D-based methods preferred the right parasternal short-axis view and indexed the LA to the aorta. Approximately 30% (n = 191) of the echocardiographers who performed linear measurements from 2D echocardiograms shared the same preferences regarding dog position, acquisition view, indexing method, and identification of the time-point used for the measurement. The responses were comparably homogeneous across geographic location, training level, years of performing echocardiography, and type of practice. DISCUSSION/CONCLUSION: Most veterinary echocardiographers assessed LA size in dogs using linear 2D echocardiography from a right parasternal short-axis view, and by indexing the LA to the aorta. The respondents' preferences were similar across geographic, demographic, and professional backgrounds.

Impact of blood tube additives and timing of sampling on blood taurine concentrations in clinically healthy dogs.

INTRODUCTION: Dilated cardiomyopathy can be associated with taurine deficiency in dogs. Blood taurine concentrations can be analyzed in whole blood (WB) and plasma. The study objectives were to investigate agreement between taurine concentrations measured in WB, heparin plasma, and EDTA plasma, determine intraindividual variation in healthy dogs, and evaluate if time from feeding to sampling impacts concentrations. ANIMALS: Ten English Cocker spaniels and 10 dogs of various breeds. MATERIALS AND METHODS: Dogs were fasted 12 h prior to initial blood sampling, and the blood was collected at five occasions over eight h. Food was offered immediately after first and one h after fourth sampling time point. RESULTS: Agreement between taurine concentrations in EDTA plasma and heparinized plasma was good (mean difference 4.5 nmol/mL, 95% confidence interval (CI) 36.8-45.8 nmol/mL). Whole blood concentrations were systematically higher than EDTA and heparin plasma concentrations (mean difference 132.7 nmol/mL, 95% CI 23.6-241.8 nmol/mL, and 127.6 nmol/mL, 95% CI 28.6-226.6 nmol/mL, respectively, all P < 0.001). Intraindividual daily variations in taurine concentration were seen in all additives, with largest variations in plasma (P < 0.001). Taurine concentration in heparinized plasma was higher at first and fifth sampling time points compared to the fourth (P = 0.014). DISCUSSION: Agreement was found between taurine concentrations measured in different additives, with expected higher concentration in WB than plasma. Taurine concentrations measured in heparinized plasma varied with sampling time point. Intraindividual daily variations were observed in all additives, but mainly in plasma samples. CONCLUSION: Taurine concentrations in dogs with suspected deficiency should be interpreted with caution.

Use of physical examination, electrocardiography, radiography, and biomarkers to predict echocardiographic stage B2 myxomatous mitral valve disease in preclinical Cavalier King Charles Spaniels.

INTRODUCTION: Cavalier King Charles Spaniels (CKCS) are predisposed to developing myxomatous mitral valve disease (MMVD). Dogs with stage B2 MMVD benefit from medication. OBJECTIVES: To develop (1) breed-specific cut-offs for individual screening tests and (2) predictive models utilizing physical examination (PE), ECG, radiograph, and blood-based biomarker variables in combination for identification of echocardiographic stage B2 MMVD in preclinical CKCS. ANIMALS: Adult, preclinical CKCS not receiving cardiac medications (N = 226). MATERIALS AND METHODS: Prospective, cross-sectional study. Enrolled CKCS underwent PE, ECG, radiography, Doppler blood pressure measurement, echocardiography, and biomarker testing. Dogs were grouped by MMVD stage using echocardiography only. The discriminatory ability of individual tests to identify stage B2 was assessed, and prediction models were developed using variables derived from four 'tests' (PE, ECG, radiography, and biomarkers). RESULTS: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and radiographic vertebral heart size (VHS) had the best discriminatory ability of individual diagnostic tests to differentiate stage A/B1 CKCS from stage B2, with an area under the curve (AUC) of 0.855 and 0.843, respectively. An NT-proBNP ≥1138 pmol/L or a VHS ≥11.5 had high specificity for predicting stage B2 (90.1% and 90.6%, respectively). Prediction models incorporating variables from multiple tests had better discriminatory ability than single tests. The four-test prediction model had an AUC of 0.971. Three and two-test models had AUCs ranging between 0.925-0.959 and 0.895-0.949, respectively. CONCLUSIONS: Both NT-proBNP and VHS have good utility for predicting echocardiographic stage B2 MMVD in CKCS as individual tests. Prediction models incorporating multiple test variables have superior discriminatory ability.

Prognostic value of selected one-, two- and three-dimensional and Doppler echocardiographic methods to assess severity in dogs with myxomatous mitral valve disease.

INTRODUCTION: Although challenging, predicting outcomes in dogs with myxomatous mitral valve disease (MMVD) is of importance to owners and veterinarians. Our aim was to compare the prognostic value of selected one-, two-, and three-dimensional and Doppler echocardiographic methods to predict cardiac-related and all-cause mortality in MMVD dogs. We hypothesize that three-dimensional methods would better predict prognosis than one- and two-dimensional methods. ANIMALS: One-hundred thirty-eight privately-owned dogs with MMVD. MATERIALS AND METHODS: Cox proportional Hazard analyses and Kaplan-Meier curves were used to investigate the predictive value of 14 variables; left atrial (LA) volume indexed to body weight (BW) measured by real-time three-dimensional echocardiography (RT3DE) and calculated using Simpson's modified method of discs (SMOD) and the area-length method; LA diameter in short-axis and long-axis to aortic in short-axis ratio, effective regurgitant orifice area indexed to body surface area measured in RT3DE en face view and calculated using four-chamber (4Ch) and two-chamber views alone or in combination; percentage increase in left ventricular end-diastolic and systolic internal diameters; fractional shortening; E wave velocity; regurgitant jet area/LA area. RESULTS: All 14 variables were significantly predictive of cardiac-related mortality, and 11 were predictive of all-cause mortality. The prognosis was best predicted by LA volume/BW estimated by SMOD or RT3DE, consistently showing the highest predictive value in all analyses. CONCLUSIONS: Left atrial volume calculated by SMOD showed a similar predictive value compared to RT3DE. Performing SMOD from apical 4Ch images should be considered an alternative to RT3DE for echocardiographic examinations where prognostication of disease outcome is sought.

Prospective evaluation of the combined value of physical examination and biomarker variables in screening for preclinical dilated cardiomyopathy in Doberman Pinschers.

INTRODUCTION: Screening to assess likelihood of preclinical dilated cardiomyopathy (PC-DCM) prior to advanced diagnostic tests in Doberman Pinschers (DP) is desirable. OBJECTIVE: To investigate the combined value of physical examination (PE), N-terminal pro B-type natriuretic peptide (NTproBNP) and cardiac troponin I (cTnI) for identifying PC-DCM in DP. ANIMALS, MATERIALS AND METHODS: All dogs underwent: PE, echocardiogram, 3-min ECG and cardiac biomarker measurement. Asymptomatic DP (414) were classified based on 3-min ECG and echocardiogram as: No-DCM/MMVD or myxomatous mitral valve disease (MMVD), PC-DCM based on echocardiogram (PC-DCM-Echo), PC-DCM based on arrhythmias with a normal echocardiogram (PC-DCM-ECG), equivocal DCM (EQ-DCM), and MMVD. Receiver operator characteristic curves and prediction models were derived. RESULTS: Heart murmurs and arrhythmias were rare and gallop sounds were absent in No-DCM/MMVD DP. Dogs ≥ four years old and males had higher probabilities of PC-DCM-Echo. Prediction models incorporating PE variables with NTproBNP had an area under the curve (AUC) of 0.940 for distinguishing between PC-DCM-Echo and all other groups, which was similar to the AUC for NTproBNP (0.939) or cTnI (0.932) alone. Discrimination between No-DCM/MMVD and all other groups was similar for NTproBNP (0.781) and cTnI (0.742) as individual tests, however, models combining PE variables and NTproBNP increased the AUC to 0.812. An NTproBNP cut-off of ≥548 pmol/L, was 100% sensitive and 77.3% specific for detecting PC-DCM-Echo. CONCLUSIONS: Both NTproBNP and cTnI had good utility as sole tests to discriminate PC-DCM-Echo DP from all others. Models differentiating No-DCM/MMVD DP from all other DP were improved by using PE and NTproBNP together.

The longitudinal outcome of canine (K9) myxomatous mitral valve disease (LOOK-Mitral) registry: Baseline treatment characteristics.

OBJECTIVES: To describe the medical treatment prescribed or modified by veterinary cardiologists at the enrollment visit in dogs included in the longitudinal outcome of canine (K9) myxomatous mitral valve disease (MMVD) registry (LOOK-mitral registry) and to evaluate the influence of the EPIC trial and other selected variables on cardiologist prescription habits. ANIMALS: The medical records of 6,102 dogs enrolled in the LOOK_mitral registry between 2015 and 2018 were retrospectively reviewed and 6,016 dogs were included. RESULTS: A medical treatment was prescribed by a cardiologist to 2,599 dogs (15% Stage-B1, 90% Stage-B2 and to all dogs in Stage-C). Angiotensin converting enzyme inhibitors (Ace-i) were the treatment most commonly prescribed for dogs in Stage-B1 (n = 352, 9%). The combination of pimobendan and an Ace-i was the most common treatment in Stage-B2 dogs (n = 367, 41%). Furosemide, an Ace-i, and pimobendan was the most common cardiac medical treatment prescribed for ACVIM Stage-C dogs (n = 704, 57%). Within each stage, dogs with larger left atrial and left ventricular dimensions were more likely to receive Ace-i, pimobendan or spironolactone. There was a four-fold increase in pimobendan prescription in Stage-B2 dogs after the publication of the EPIC trial. Moreover, a 15% reduction in Ace-i prescription and a 30% reduction in spironolactone prescription occurred after EPIC. In 974 dogs, a medical treatment was prescribed by the referring veterinarian. This was not changed (12%), modified (74%), or discontinued (14%) by the cardiologist. CONCLUSIONS: The EPIC trial and the echocardiographic assessment of left atrial and ventricular dimensions influence cardiologists' prescription habits.

Prediction of clinically important acquired cardiac disease without an echocardiogram in large breed dogs using a combination of clinical, radiographic and electrocardiographic variables.

INTRODUCTION: Large breed (LB) dogs develop dilated cardiomyopathy (DCM) and myxomatous mitral valve disease (MMVD). Echocardiography is required for a definitive diagnosis but is not always available. Our objective was to assess the clinical utility of thoracic radiographs alone and in combination with physical examination and electrocardiography findings for the prediction of clinically important DCM or MMVD in LB dogs. ANIMALS: Four hundred fifty-five client-owned dogs ≥20 kg with concurrent thoracic radiographs and echocardiogram. MATERIALS AND METHODS: Medical records were reviewed and stored thoracic radiographs and echocardiographic images were measured to classify dogs as normal heart size (NHS), preclinical DCM, clinical DCM, preclinical MMVD (with cardiomegaly), clinical MMVD, or equivocal. Dogs with preclinical MMVD, without cardiomegaly, were classified as NHS. Vertebral heart size (VHS) and vertebral left atrial size (VLAS) were measured. Receiver operating characteristic curves and prediction models were derived. RESULTS: Prevalence of MMVD (39.3%) was higher than the prevalence of DCM (24.8%), though most MMVD dogs (67.0%) lacked cardiomegaly and were classified as NHS for analysis. The area under the curve for VHS to discriminate between NHS and clinical DCM/MMVD or preclinical DCM/MMVD was 0.861 and 0.712, respectively, while for VLAS, it was 0.891 and 0.722, respectively. Predictive models incorporating physical examination and electrocardiography findings in addition to VHS/VLAS increased area under the curve to 0.978 (NHS vs. clinical DCM/MMVD) and 0.829 (NHS vs. preclinical DCM/MMVD). CONCLUSIONS: Thoracic radiographs were useful for predicting clinically important DCM or MMVD in LB dogs, with improved discriminatory ability when physical examination abnormalities and arrhythmias were accounted for.

The Longitudinal Outcome Of Canine (K9) myxomatous mitral valve disease (LOOK-Mitral registry): Baseline characteristics.

INTRODUCTION: The Longitudinal Outcome Of Canine (K9) myxomatous mitral valve disease (MMVD) registry (LOOK-Mitral registry) was established to describe the natural history and predictors of outcome in dogs affected by MMVD. This study was intended to describe the baseline characteristics of dogs in the LOOK-mitral registry. ANIMALS: Dogs with echocardiographic evidence of MMVD were prospectively enrolled by thirteen referral centers. RESULTS: A total of 6102 dogs with MMVD were included. The median age was 10 years (1-19 years), and mixed breed was the most common breed (n = 1,360, 22%). Concomitant diseases were reported in 2459 dogs with chronic respiratory diseases occurring most frequently (14%), followed by the presence of azotemia (6%) and orthopedic diseases (5%). Regarding disease severity, 65% of dogs were in ACVIM Stage-B1, 15% in Stage-B2, and 20% in Stage-C. Dogs in Stage-B1 were younger (p<0.001) than dogs in other stages. Murmur intensity, heart rate during physical examination, and radiographic vertebral heart score were positively associated with the stage. Dogs in Stage-C were more likely to have tachypnea (p<0.001), dyspnea (p<0.001), cough (p<0.001), syncopal episodes (p<0.001), and tachyarrhythmias (p<0.001) compared to dogs in Stage-B1 and B2. Echocardiographic indices of left atrial and ventricular size were positively correlated with the ACVIM stage. Interestingly, 4% of dogs that weighed <20 kg had an increased normalized end-systolic left ventricle internal diameter (>1.26). CONCLUSIONS: This study contributes to a better understanding of the clinical characteristics of dogs affected by MMVD and provides new findings that may be of clinical relevance.

Predictors of reoccurrence of congestive signs within 180 days after successful treatment of the first episode of congestive heart failure in dogs with myxomatous mitral valve disease.

INTRODUCTION: Myxomatous mitral valve disease (MMVD) is the most common cause of left-sided congestive heart failure in dogs. We sought to identify predictors of first reoccurrence of congestive signs (CS) within 180 days in dogs with MMVD and clinically stable heart failure. ANIMALS: A total of 445 dogs affected by stable American College of Veterinary Internal Medicine (ACVIM)-Stage-C MMVD were included, 106 in the reoccurrence group (RG) and 339 in no reoccurrence group (NRG). Patients were considered "stable" if medical treatment had been unchanged for at least 4 weeks since the first identification of CS. METHODS: Medical records of dogs with stable ACVIM-Stage-C MMVD included in a registry of dogs affected by MMVD were reviewed. Follow-up was required for inclusion in this investigation. Logistic regression was used to identify clinical and echocardiographic variables that independently predict first reoccurrence of CS. RESULTS: Baseline left atrial-aortic ratio (p=0.022, OR: 1.89, 90% CI: 1.20-2.98), left ventricular internal diameter at end-diastole (LVIDd_N) (p=0.014, OR: 2.84, 90% CI: 1.41-5.77), peak velocity of early diastolic transmitral flow (p=0.049, OR: 1.81, 90% CI: 1.10-3.00) and furosemide daily dosage (p=0.039, OR: 1.19, 90% CI: 1.04-1.37) were associated with reoccurrence of CS in univariable analyses. The LVIDd_N (p=0.014) remained significant in the multivariable analysis, but the area under the receiver operator characteristic curve was 0.57. CONCLUSION: This study failed to identify accurate predictors of reoccurrence of CS. However, dogs with larger value of LVIDd_N are more likely to have reoccurrence of CS within 180 days.

Comparisons of 3-, 2-dimensional, and M-mode echocardiographical methods for estimation of left chamber volumes in dogs with and without acquired heart disease.

BACKGROUND: Real-time 3-dimensional echocardiography (RT3D) is a recent technique based on volumetric scanning, eliminating the need for geometric modeling of the cardiac chambers and minimizing the errors caused by foreshortened views. HYPOTHESIS: Estimations of left ventricular (LV) end-diastolic (EDV) and end-systolic volume (ESV), and left atrial (LA) size, differ depending on the echocardiographic technique of estimation. ANIMALS: Fifty-one dogs with acquired heart disease and 34 healthy control dogs. METHODS: Prospective observational study by M-mode (Teichholz method), Simpson's modified 2-dimensional (2D) method, and RT3D methods for estimation of LV volumes. LA size was evaluated by 2D and RT3D methods. RESULTS: RT3D showed good agreement with 2D for EDV and ESV, whereas Teichholz method overestimated LV volumes in comparison with the other 2 methods by approximately a factor 2. There were no statistically significant differences among the 3 methods in estimating ejection fraction. Comparison between RT3D assessment of LA end-systolic volume per kilogram (LAs/kg) and LA to aortic ratio (LA/Ao) measured by 2D relative to each other showed that the RT3D method underestimated LAs/kg at lower values, and overestimated it at higher values. The difference between methods increased with increasing LA size. CONCLUSIONS AND CLINICAL IMPORTANCE: There was good agreement between RT3D and 2D methods of estimating EDV and ESV, whereas the Teichholz method overestimated LV volumes by approximately a factor 2. In comparison with RT3D, LA/Ao underestimated LA size, especially when LA was enlarged.

Pulmonary blood volume in mitral regurgitation in Cavalier King Charles spaniels.

BACKGROUND: Pulmonary edema and venous congestion are well-recognized signs of congestive heart failure (CHF) in advanced canine chronic mitral regurgitation (MR). However, little is known about pulmonary blood volume (PBV), blood pulmonary transit time (PTT), and the regulation of these. OBJECTIVES: To measure and evaluate the relationships of PBV, forward stroke volume (FSV), and heart rate normalized blood pulmonary transit time (nPTT) in healthy dogs and dogs with MR. ANIMALS: Thirty-three Cavalier King Charles Spaniels; 11 healthy, 4 in modified New York Heart Association (NYHA) class I, 11 in class II, and 7 in CHF. METHODS: Heart rate normalized PTTs were measured by radionuclide angiocardiography. Left ventricular end diastolic and systolic diameter, left atrial/aortic root ratio, and FSV were measured by echocardiography. PBV and pulmonary blood volume index (PBVI) were calculated by established formulas. RESULTS: PBVI was 308±56 (mean±SD) mL/m2 for healthy dogs, 287±51 mL/m2 in NYHA class I, 360±66 mL/m2 in Class II, and 623±232 mL/m2 in CHF (P=.0008). Heart rate normalized PTT, not FSV, was a predictor of PBV (r=0.92 and 0.02, respectively). CONCLUSIONS AND CLINICAL IMPORTANCE: Increased PBV, not decreased FSV, is the main cause of increased nPTT in MR. Increased nPTT can be used as an indicator of abnormal cardiopulmonary function in dogs with MR.

Cardiac troponin I is associated with severity of myxomatous mitral valve disease, age, and C-reactive protein in dogs.

BACKGROUND: Concentrations of cardiac troponin I (cTnI) and C-reactive protein (CRP) might be associated with cardiac remodeling in dogs with myxomatous mitral valve disease (MMVD). Age- and sex-dependent variations in cTnI concentration have been described. OBJECTIVE: To investigate whether plasma concentrations of cTnI and CRP are associated with severity of MMVD, and investigate potential associations of dog characteristics on cTnI and CRP concentrations. ANIMALS: Eighty-one client-owned dogs with MMVD of varying severity. METHODS: Dogs were prospectively recruited for the study. Dogs were classified according to severity of MMVD. Plasma cTnI was analyzed by a high sensitivity cTnI assay with a lower limit of detection of 0.001 ng/mL, and plasma CRP was analyzed by a canine-specific CRP ELISA. RESULTS: Higher cTnI concentrations were detected in dogs with moderate (0.014 [interquartile range 0.008-0.029] ng/mL, P = .0011) and severe (0.043 [0.031-0.087] ng/mL, P < .0001) MMVD, compared with healthy dogs (0.001 [0.001-0.004]ng/mL). Dogs with severe MMVD also had higher cTnI concentrations than dogs with mild (0.003 [0.001-0.024] ng/mL, P < .0001) and moderate (P = .0019) MMVD. There were significant associations of age, CRP, heart rate, and left ventricular end-diastolic diameter, on cTnI concentration C-reactive protein did not differ among severity groups, but was significantly associated with cTnI, breed, and systolic blood pressure on CRP concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Analysis of cTnI concentration has potential to increase knowledge of overall cardiac remodeling in dogs with MMVD. However, effect of age on cTnI needs consideration when assessing cTnI.

Efficacy of spironolactone on survival in dogs with naturally occurring mitral regurgitation caused by myxomatous mitral valve disease.

BACKGROUND: Spironolactone, an aldosterone antagonist, has been demonstrated to decrease mortality in human patients when added to other cardiac therapies. HYPOTHESIS: Spironolactone in addition to conventional therapy increases survival compared with conventional therapy in dogs with naturally occurring myxomatous mitral valve disease (MMVD). ANIMALS: Between February 2003 and March 2005, 221 dogs were recruited in Europe. Nine dogs were excluded from analysis, leaving 212 dogs with moderate to severe mitral regurgitation (MR) caused by MMVD (International Small Animal Cardiac Health Council classification classes II [n = 190] and III [n = 21]). METHODS: Double-blinded, field study conducted with dogs randomized to receive either spironolactone (2 mg/kg once a day) or placebo in addition to conventional therapy (angiotensin converting enzyme inhibitor, plus furosemide and digoxin if needed). Primary endpoint was a composite of cardiac-related death, euthanasia, or severe worsening of MR. RESULTS: Primary endpoint reached by 11/102 dogs (10.8%) in the spironolactone group (6 deaths, 5 worsening) versus 28/110 (25.5%) in control group (14 deaths, 8 euthanasia, 6 worsening). Risk of reaching the composite endpoint significantly decreased by 55% (hazard ratio [HR] = 0.45; 95% confidence limits [CL], 0.22-0.90; log rank test, P = .017). Risk of cardiac-related death or euthanasia significantly reduced by 69% (HR = 0.31; 95% CL, 0.13-0.76; P = .0071). Number of dogs not completing the study for cardiac and other miscellaneous reasons similar in spironolactone (67/102) and control groups (66/110). CONCLUSION AND CLINICAL IMPORTANCE: Spironolactone added to conventional cardiac therapy decreases the risk of reaching the primary endpoint (ie, cardiac-related death, euthanasia, or severe worsening) in dogs with moderate to severe MR caused by MMVD.

Intermittent mitral regurgitation in Cavalier King Charles spaniels: Short-term progression and influence of stress tests.

In young Cavalier King Charles spaniels (CKCS), intermittent mitral regurgitation (iMR; defined as moderate to severe mitral regurgitation [MR] in a small proportion of heartbeats), has been associated with an increased risk of cardiac death due to myxomatous mitral valve disease (MMVD). It is associated with increased R-R interval variability. Little is known about response to physiological factors and whether iMR is a precursor for developing significant MR. The aim of this study was to determine the effect of stress testing on the presence of iMR and heart rate, and short-term (1-2 year) progression of MR in CKCS with and without iMR. In total, 52 CKCS were included. Substudy 1 enrolled six dogs with iMR and 11 dogs without iMR. Substudy 2 enrolled 14 dogs with iMR and 28 dogs without iMR. Substudy 1 prospectively assessed the influence of stress testing on the presence of iMR and heart rate. Substudy 2 retrospectively evaluated short-term progression of iMR. During stress testing, iMR disappeared in 50% of CKCS and no iMR was recorded at mean heart rates >150 beats/min. Heart rate response did not differ between CKCS with or without iMR. CKCS with iMR did not have a higher odds (odds ratio = 5.2; 95% confidence interval, 0.7-38.2) of MR progression compared to controls (P = 0.1). In conclusion, physical stress influenced the occurrence of iMR in CKCS, but heart rate response was not different from CKCS without iMR. Intermittent mitral regurgitation did not significantly predict short-term MR progression. In stressed CKCS with early disease, iMR may be overlooked.

Surfactant protein C in canine pulmonary fibrosis.

BACKGROUND: Canine pulmonary fibrosis (CPF) occurs most commonly in West Highland White Terriers. The differing incidences of CPF among dog breeds suggest that genetic factors contribute to its pathophysiology. Pulmonary fibrosis in humans is associated with mutations in the gene coding for lung surfactant protein C (SP-C) (SFTPC). HYPOTHESIS/OBJECTIVES: To investigate the histopathologic changes and SP-C composition and genetic structure in dogs with CPF. ANIMALS: Five dogs with PF, 2 dogs with other lung diseases, and 3 healthy dogs. METHODS: Lung tissue from dogs with clinically suspected CPF and 5 control cases was analyzed histopathologically. Bronchoalveolar lavage fluid (BALF) collected postmortem from 3 terriers with histopathologically confirmed pulmonary fibrosis and the 5 controls were analyzed by Western blots, and the exons of SFTPC were sequenced for 2 dogs with PF and 1 dog with other lung disease. RESULTS: SP-C could not be detected in BALF of 1 dog with PF, although SP-B was present. A mutation was detected in SFTPC exon 5 of this dog. From 2 dogs with PF and in all 5 control dogs SP-B and SP-C were detected in BALF. CONCLUSIONS: Taken together, the results indicate that canine and human lung fibrosis share histopathologic features and that analysis of SP-C and its gene in a larger set of dogs with PF is warranted.

Analysis of 8 sarcomeric candidate genes for feline hypertrophic cardiomyopathy mutations in cats with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats. Causative mutations have been identified in the Maine Coon (MC) and Ragdoll breed in the cardiac myosin binding protein C gene (MYBPC3). HCM is thought to be inherited in other breeds. HYPOTHESIS: That a causative mutation for HCM in the British Shorthair (BSH), Norwegian Forest (NWF), Siberian, Sphynx, or MC cats would be identified in the exonic and splice site regions of 1 of 8 genes associated with human familial HCM. ANIMALS: Three affected BSH, NWF, Siberians, Sphynx, 2 MC (without the known MC mutation), and 2 Domestic Shorthair cats (controls) were studied. METHODS: Prospective, observational study. Exonic and splice site regions of the genes encoding the proteins cardiac troponin I, troponin T, MYBPC3, cardiac essential myosin light chain, cardiac regulatory myosin light chain, alpha tropomyosin, actin, and beta-myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected cats, the published DNA sequences, and control cats. Changes were considered to be causative for HCM if they involved a conserved amino acid and changed the amino acid to a different polarity, acid-base status, or structure. RESULTS: A causative mutation for HCM was not identified, although several single nucleotide polymorphisms were detected. CONCLUSIONS AND CLINICAL IMPORTANCE: Mutations within these cardiac genes do not appear to be the only cause of HCM in these breeds. Evaluation of additional cardiac genes is warranted to identify additional molecular causes of this feline cardiac disease.

Size and shape of right heart chambers in mitral valve regurgitation in small-breed dogs.

BACKGROUND: The contribution of right heart (RH) chamber enlargement to general heart enlargement seen on thoracic radiographs in mitral regurgitation (MR) is not known. OBJECTIVES: To determine the size and shape of the RH chambers in normal dogs and dogs with varying degrees of MR. ANIMALS: Fifty-four privately owned dogs: 13 normal, 41 with varying degrees of MR including 25 with congestive heart failure (CHF). METHODS: Archived first pass radionuclide angiocardiograms were used to produce static images of the RH and left heart (LH) chambers. Indexes of size and shape of the RH and LH chambers were related to severity of MR determined by heart rate-normalized pulmonary transit time (nPTT), vertebral heart scale (VHS), and clinical status. RH shape was measured by a circularity index of RH short axis/long axis. RESULTS: A 2nd degree polynomial fit best described the ratios; RH/LH dimension to nPTT (R(2)= 0.62) and to VHS (R(2)= 0.43), RH/LH area to nPTT (R(2)= 0.64) and to VHS (R(2)= 0.58), all P < .001. RH circularity was decreased in CHF, P < .001. In CHF, the RH chambers of 16 dogs were both flattened and enlarged, whereas 9 had convex septal borders. CONCLUSIONS: RH chambers are not significantly dilated in dogs with mild to moderate MR without CHF. In CHF, RH chambers enlarge and also may be compressed by the LH chambers. Pulmonary hypertension probably is present in some dogs with CHF. Increased sternal contact is not a useful sign of right-sided heart dilatation in MR.

Mortality of life-insured Swedish cats during 1999-2006: age, breed, sex, and diagnosis.

BACKGROUND: A cat life insurance database can potentially be used to study feline mortality. HYPOTHESIS: The aim was to describe patterns of mortality in life-insured Swedish cats. Cats: All cats (<13 years of age) with life insurance during the period 1999-2006 were included. METHODS: Age-standardized mortality rates (MR) were calculated with respect to sex (males and females), age, breed, and diagnosis. Survival to various ages is presented by time period and breed. RESULTS: The total number of cats insured was 49,450 and the number of cat-years at risk (CYAR) was 142,049. During the period, 6,491 cats died and of these 4,591 cats (71%) had a diagnosis, ie, were claimed for life insurance. The average annual MR was 462 deaths per 10,000 CYAR (95% confidence interval, 431-493). Sex-specific rates did not differ significantly. The overall mortality of the Persian and the Siamese groups was higher than that of several other breeds. Overall and breed-specific (for most breeds) survival increased with time when analyzed by 2-year periods. The 6 most common diagnostic categories (ignoring cats recorded as dead with no diagnosis) were urinary, traumatic, neoplastic, infectious, cardiovascular, and gastrointestinal. The MR within diagnostic categories varied by age and breed. CONCLUSIONS AND CLINICAL IMPORTANCE: In this mainly purebred, insured cat population, the overall mortality varied with age and breed but not with sex. The increase in survival over time is likely a reflection of willingness to keep pet cats longer and increased access to and sophistication of veterinary care.