Kerstin Hansson

Relationship between different natriuretic peptides and severity of naturally acquired mitral regurgitation in dogs with chronic myxomatous valve disease.

OBJECTIVE To study the responses of atrial natriuretic peptide (ANP), N-terminal fragment of pro-atrial natriuretic peptide (NT-proANP) and brain natriuretic peptide (BNP) to varying severity of mitral regurgitation (MR) in dogs with myxomatous valve disease (MVD). DESIGN Case-control. DOGS: 103 Cavalier King Charles Spaniels, 27 normal individuals and 76 with varying degree of MR. PROCEDURE Dogs were evaluated by physical examination, collection of venous blood, thoracic radiography and echocardiography. NT-proANP, ANP and BNP were measured in plasma using radio immunoassay (RIA). RESULTS The mean concentrations of NT-proANP were 37.4 and 83.5 times higher than ANP and BNP, respectively. The mean ANP to BNP molar ratio was 2.6. Plasma concentrations of NT-proANP and ANP were slightly increased in asymptomatic dogs with increased cardiac dimensions; those with signs of decompensated heart failure (HF) had mean concentrations of NT-proANP and ANP 3 to 7 times higher than normal dogs. The BNP concentrations were increased only in dogs with decompensated HF and the levels were approximately twice as high in these dogs as in normal individuals. Univariate and multiple regression analysis showed that primarily left atrial and ventricular size influenced the plasma concentrations of all 3 peptides (increased with increasing measurement). Analyses of response operating characteristic (ROC) curves indicated that NT-proANP and ANP were more discriminating than BNP for either cardiomegaly of HF. CLINICAL IMPLICATIONS Natriuretic peptides, particularly NT-proANP and ANP, may be of benefit in the overall assessment of dogs with naturally occurring MR. Analysis of NT-proANP may be more useful than ANP owing to easier handling of the samples and less laborious assay.

Rate of change of heart size before congestive heart failure in dogs with mitral regurgitation

OBJECTIVES The objective of the study was to examine the changes in vertebral heart scale, and left atrial and ventricular dimensions before and at onset of congestive heart failure in cavalier King Charles spaniels with mitral regurgitation. METHODS Records and radiographs from 24 cavalier King Charles spaniels with mitral regurgitation were used. Vertebral heart scale (24 dogs), and left atrial dimension and left ventricular end diastolic and end systolic diameters (18 dogs) and their rate of increase were measured at intervals over years to the onset of congestive heart failure. They were plotted against time to onset of congestive heart failure. RESULTS Dimensions and rates of change of all parameters were highest at onset of congestive heart failure, the difference between observed and chance outcome being highly significant using a two-tailed chi-square test (P<0.001). CLINICAL SIGNIFICANCE The left heart chambers increase in size rapidly only in the last year before the onset of congestive heart failure. Increasing left ventricular end systolic dimension is suggestive of myocardial failure before the onset of congestive heart failure. Rate of increase of heart dimensions may be a useful indicator of impending congestive heart failure.

Reader performance in radiographic diagnosis of signs of mitral regurgitation in cavalier King Charles spaniels

OBJECTIVES To measure accuracy and variability of diagnosis by radiography of heart enlargement (HE) and heart failure (HF) in mitral regurgitation (MR). METHODS Sixteen readers representing four levels of experience evaluated 50 sets of radiographs with varying severity of MR for presence or absence of HE, left atrial enlargement (LAE) and HF. The performance of the readers was compared with a reference standard, using area under the curve (AUC) of receiver operating characteristic (ROC) curves. The interreader agreement value kappa (K) was calculated. A subset of difficult cases of HF was analysed before and after removing an outlying reader from each group. RESULTS AUC for HE was 0.89, for LAE it was 0.93 and for HF it was 0.92. Experience increased certainty of diagnosis but not accuracy. K ranges were HE, 0.53 to 0.67; LAE, 0.61 to 0.69 and HF, 0.49 to 0.58. When only difficult cases of HF were read, accuracy decreased and experienced readers performed better than inexperienced. When outlying readers were excluded, the differences between experienced and inexperienced readers increased. CLINICAL SIGNIFICANCE LAE, not HE, should be used to evaluate the heart size and indirectly the severity of MR on radiographs. For HF, agreement among individual readers was only moderate. Studies of reader accuracy should consider the effects of interreader variability.

Radiographic heart size and its rate of increase as tests for onset of congestive heart failure in Cavalier King Charles Spaniels with mitral valve regurgitation.

BACKGROUND In canine mitral regurgitation (MR) the rate of heart enlargement increases in the last year before congestive heart failure (CHF). Measurement of heart size and its rate of increase may be useful tests for CHF in MR. OBJECTIVES To determine the value of vertebral heart scale (VHS) and its rate of increase (∆VHS units/month) for diagnosing the presence and predicting the onset of CHF. ANIMALS Longitudinal study of 94 Cavalier King Charles Spaniels (CKCS). METHODS VHS was measured at intervals before CHF. ∆VHS/month was calculated from sequential pairs of VHS measurements and the interval between them. Diagnostic accuracy and utility were determined by the areas under receiver operating characteristic plots (AUROC), and likelihood ratios (LR). RESULTS AUROC for VHS at the onset of CHF was 0.93 (95% CI, 0.96-0.90), to predict CHF 1-12 months before CHF was 0.74 (95% CI, 0.81-0.66), and for ∆VHS/month at CHF was 0.98 (95% CI, 0.99-0.96). Interval LRs and their cutoff values for CHF were for VHS: 13 (95% CI, 20-7.3) at ≥12.7; 1.2 (95% CI, 2.0-0.68) between 12.7 and 12.0; 0.04 (95% CI, 0.18-0.01) at ≤12.0, and for ∆VHS/month: 15 (95% CI, 30-7.7) at ≥0.08; 0.72 (95% CI, 2.0-0.25) between 0.08 and 0.06; and 0.05 (95% CI, 0.13-0.02) at ≤0.06. CONCLUSIONS AND CLINICAL IMPORTANCE Under the conditions of this study, VHS and particularly ∆VHS/month are useful measurements for detecting onset of CHF in CKCS with MR.

Short‐Term Hemodynamic and Neuroendocrine Effects of Pimobendan and Benazapril in Dogs with Myxomatous Mitral Valve Disease and Congestive Heart Failure

BACKGROUND Pimobendan and benazepril are frequently used with diuretics to treat dogs in congestive heart failure (CHF) caused by myxomatous mitral valve disease (MMVD). AIM To compare the short-term effects of pimobendan versus benazepril on pump function, heart size, and neuroendocrine profile in dogs with CHF caused by MMVD. ANIMALS Sixteen client-owned dogs. MATERIAL AND METHODS Seven-day prospective single-blinded study of dogs stabilized on furosemide monotherapy, randomized to pimobendan (0.4-0.6 mg/kg/day) or benazepril (0.25-1.0 mg/kg/day). Dogs had first-pass radionuclide angiocardiography, and heart size was measured by radiography and echocardiography. Circulating neuroendocrine hormones were measured. RESULTS Baseline variables did not differ between treatment groups. Greater decreases in the pimobendan than in the benazepril group were found for heart rate (P = .001), heart rate-normalized pulmonary transit time (P = .02), left atrial size (P = .03), and systolic and diastolic left ventricular diameters (P < .001 and P = .03, respectively) and volumes (P < .001 and P = .02, respectively), whereas ejection fraction increased more (P = .02) in the pimobendan group. Of the neuroendocrine hormones, only N-terminal proatrial natriuretic peptide (NT-ProANP) differed (P = .04) between groups. Within groups, plasma aldosterone increased (P = .01), and NT-proANP (P = .01) and NT-proB-type (P = .02) natriuretic peptide decreased in the pimobendan group, and NT-proANP (P = .02) and plasma vasopressin (P = .01) decreased in the benazepril group. CONCLUSIONS AND CLINICAL IMPORTANCE Pimobendan improves short-term cardiac function more than benazepril in dogs with CHF caused by MMVD. Pimobendan treatment enables the heart to work at smaller end-systolic and diastolic dimensions while maintaining adequate forward stroke volume. Some of the treatment responses found in neuroendocrine profile might have therapeutic relevance.

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.

Evaluation of osteochondral sample collection guided by computed tomography and magnetic resonance imaging for early detection of osteoarthritis in centrodistal joints of young Icelandic horses.

OBJECTIVE To evaluate the use of CT and MRI for guidance of osteochondral sample collection for histologic detection of early osteoarthritic lesions in centrodistal (distal intertarsal) joints of horses. SAMPLE Right tarsal joints from the cadavers of 24 Icelandic horses aged 29 to 31 months. PROCEDURES CT and MRI were used to evaluate the extent of suspected osteoarthritic changes in centrodistal joints, which were graded with a semiquantitative system. The anatomic regions with the highest grade of change were identified, and osteochondral samples were obtained from these regions. Samples were also obtained from the same centrodistal joints at predetermined sites. Histologic examination of all samples was performed, with samples classified as negative or positive for osteoarthritis, and results were compared between sample collection methods. RESULTS Histologic examination revealed osteoarthritic lesions in 29% (7/24) of centrodistal joints with the predetermined method and in 63% (15/24) with the image-guided method. Significant associations were identified between histologic osteoarthritis detection and the summed image-guided sample collection site image grades, central osteophytes, articular cartilage thickness abnormalities, grade 2 articular mineralization front defects, and grade 2 marginal osteophytes. CONCLUSIONS AND CLINICAL RELEVANCE CT and MRI aided the detection of focal changes suggestive of early-stage osteoarthritis in the centrodistal joints of equine cadavers and may be useful for detection of similar disease in live horses. The first morphological changes of centrodistal joint osteoarthritis were suspected to be in the articular cartilage and the articular mineralization front regions.

Online dosimetry for temoporfin-mediated interstitial photodynamic therapy using the canine prostate as model.

Abstract. Online light dosimetry with real-time feedback was applied for temoporfin-mediated interstitial photodynamic therapy (PDT) of dog prostate. The aim was to investigate the performance of online dosimetry by studying the correlation between light dose plans and the tissue response, i.e., extent of induced tissue necrosis and damage to surrounding organs at risk. Light-dose planning software provided dose plans, including light source positions and light doses, based on ultrasound images. A laser instrument provided therapeutic light and dosimetric measurements. The procedure was designed to closely emulate the procedure for whole-prostate PDT in humans with prostate cancer. Nine healthy dogs were subjected to the procedure according to a light-dose escalation plan. About 0.15  mg/kg temoporfin was administered 72 h before the procedure. The results of the procedure were assessed by magnetic resonance imaging, and gross pathology and histopathology of excised tissue. Light dose planning and online dosimetry clearly resulted in more focused effect and less damage to surrounding tissue than interstitial PDT without dosimetry. A light energy dose–response relationship was established where the threshold dose to induce prostate gland necrosis was estimated from 20 to 30  J/cm2.

Detection of early osteoarthritis in the centrodistal joints of Icelandic horses: Evaluation of radiography and low-field magnetic resonance imaging

REASONS FOR PERFORMING STUDY Validated noninvasive detection methods for early osteoarthritis (OA) are required for OA prevention and early intervention treatment strategies. OBJECTIVES To evaluate radiography and low-field magnetic resonance imaging (MRI) for the detection of early stage OA osteochondral lesions in equine centrodistal joints using microscopy as the reference standard. STUDY DESIGN Prospective imaging of live horses and imaging and microscopy of cadaver tarsal joints. METHODS Centrodistal (distal intertarsal) joints of 38 Icelandic research horses aged 27-29 months were radiographed. Horses were subjected to euthanasia approximately 2 months later and cadaver joints examined with low-field MRI. Osteochondral joint specimens were classified as negative or positive for OA using light microscopy histology or scanning electron microscopy. Radiographs and MRIs were evaluated for osteochondral lesions and results compared with microscopy. RESULTS Forty-two joints were classified OA positive with microscopy. Associations were detected between microscopic OA and the radiography lesion categories; mineralisation front defect (P<0.0001), joint margin lesion (P<0.0001), central osteophyte (P = 0.03) and the low-field MRI lesion categories; mineralisation front defect (P = 0.01), joint margin lesion (P = 0.02) and articular cartilage lesion (P = 0.0003). The most frequent lesion category detected in microscopic OA positive joints was the mineralisation front defect in radiographs (28/42 OA positive joints, specificity 97%, sensitivity 67%). No significant differences were detected between the sensitivity and specificity of radiography and low-field MRI pooled lesion categories, but radiography was often superior when individual lesion categories were compared. CONCLUSIONS Early stage centrodistal joint OA changes may be detected with radiography and low-field MRI. Detection of mineralisation front defects in radiographs may be a useful screening method for detection of early OA in centrodistal joints of young Icelandic horses.

Increased NT-proANP predicts risk of congestive heart failure in Cavalier King Charles spaniels with mitral regurgitation caused by myxomatous valve disease.

OBJECTIVES To evaluate the predictive value of plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and nitric oxide end-products (NOx) as markers for progression of mitral regurgitation caused by myxomatous mitral valve disease. ANIMALS Seventy-eight privately owned Cavalier King Charles spaniels with naturally occurring myxomatous mitral valve disease. METHODS Prospective longitudinal study comprising 312 measurements over a 4.5 year period. Clinical values were recorded, NT-proANP concentrations were measured by radioimmunoassay, and NOx were analyzed colorimetrically. To predict congestive heart failure (CHF), Cox proportional hazards models with time-varying covariates were constructed. RESULTS The hazard ratio for NT-proANP (per 1000 pmol/l increase) to predict future CHF was 6.7 (95% confidence interval, 3.6-12.5; p < 0.001). The median time to CHF for dogs with NT-proANP levels >1000 pmol/l was 11 months (95% confidence interval, 5.6-12.6 months), compared to 54 months (46 - infinity) for dogs with concentrations ≤ 1000 pmol/l (p < 0.001). Due to intra- and inter-individual variability, most corresponding analyses for NOx were insignificant but dogs reaching CHF had a lower mean NOx concentration than dogs not reaching CHF (23 vs. 28 μmol/l, p = 0.016). Risk of CHF increased with increase in heart rate (>130 beats per minute) and grade of murmur (≥ 3/6). CONCLUSIONS The risk of CHF due to mitral regurgitation is increased in dogs with blood NT-proANP concentrations above 1000 pmol/l. Measurement of NT-proANP can be a valuable tool to identify dogs that may develop CHF within months.