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.

Urine 5-hydroxyindoleacetic acid in Cavalier King Charles spaniels with preclinical myxomatous mitral valve disease.

Higher concentrations of circulating serotonin have been reported in Cavalier King Charles spaniels (CKCS) compared to other dog breeds. The CKCS is also a breed highly predisposed to myxomatous mitral valve disease (MMVD). The aim of this study was to determine urine concentrations of 5-hydroxyindoleacetic acid (5-HIAA), the major metabolite and excretion product of serotonin, in a population of CKCS with preclinical MMVD, and to evaluate whether urine 5-HIAA concentrations were associated with MMVD severity, dog characteristics, setting for urine sampling, platelet count, and serotonin concentration in serum and platelet-poor plasma (PPP). The study population consisted of 40 privately-owned CKCS (23 females; 17 males) with and without preclinical MMVD as follows: American College of Veterinary Internal Medicine (ACVIM) group A (n = 11), ACVIM group B1 (n = 21) and ACVIM group B2 (n = 8). Urine 5-HIAA concentrations were not significantly associated with preclinical MMVD disease, platelet count or circulating concentrations of serotonin (in serum and PPP; P > 0.05). Females had higher 5-HIAA concentrations than males in morning urine collected at home (females, 3.1 [2.9-3.7] µmol/mmol creatinine [median and quartiles]; males, 1.7 [1.2-2.2] µmol/mmol creatinine; P = 0.0002) and urine collected at the clinic (females, 3.5 [3.1-3.9] µmol/mmol creatinine; males, 1.6 [1.3-2.1] µmol/mmol creatinine; P < 0.0001). Five-HIAA concentrations in urine collected at home and at the clinic were significantly associated (P = 0.0004; r = 0.73), and higher concentrations were found in urine collected at the clinic (P = 0.013). Urine 5-HIAA concentration was influenced by sex and setting of urine sampling. Urine 5-HIAA concentration was not associated with MMVD severity or circulating concentrations of serotonin in CKCS with preclinical disease.

The biomechanical properties of the urethra in boys with hypospadias: a preliminary study.

PURPOSE: The ventral aspect of the penis in boys with hypospadias is composed of dysplastic tissue of the skin and the urethra. The aim of this study was to assess the pre-operative size and biomechanical properties of urethrae in boys with and without hypospadias using a more objective catheter-based system. MATERIALS & METHODS: In this non-blinded clinical observation study, the study population consisted of 19 boys with hypospadias-the case group (median age 13.9 months [range: 12.2-21.3])-and seven boys without hypospadias-the control group (median age 8.5 months [range: 3.8-18.1]). Modified measurements of impedance were used to assess the size, compliance and viscoelasticity of the urethrae under stepwise increased pressures (between 0, 40 and 60 cmH2O) using a customised Endolumenal Functional Lumen Imaging probe (EndoFLIP®). RESULTS: The sizes of the urethrae in boys with hypospadias are variable but tend towards being narrower and less compliant than those of the control subjects i.e. median diameter for meatus urethra was 3.2 mm (range: 2.98-3.92) in the hypospadias group compared with 3.64 (range: 3.22-4.44) in the control group at 40 cmH2O, and the median change in diameter at meatus urethra was 0.08 mm (range: -0.02 to 0.52) in the hypospadias group compared with 0.23 mm (range: -0.02 to 0.34) when the pressure was increased from 40 to 60 cmH2O. This biomechanical analysis found that there was no significant viscoelasticity of the urethral meatus in both the groups, whereas the remainder of the urethral structure generally had viscoelastic properties in the control group, seen as a creep on the time/diameter curves (Figure). In the group of boys with hypospadias, evaluations of the urethrae revealed varying viscoelastic abilities, ranging from abilities that were comparable with those of the control subjects to no sign of viscoelasticity at all. CONCLUSIONS: This study is the first to measure the biomechanical properties of the urethra in children, which might help to provide an understanding as to the structural and functional changes associated with hypospadias. The urethrae in the subjects with hypospadias were variable in diameter but tended to be narrower overall, especially in the distal portion of the urethra. Furthermore, the urethrae in boys with hypospadias were frequently less viscoelastic than those of controls. CLINICAL RELEVANCE: The EndoFLIP® system may be a future way of objectively estimating the severity of a urethral obstruction and could potentially be included in the postoperative assessment of patients with signs of hampered voiding.

Development of contractile properties in the fetal porcine urinary bladder.

BackgroundIn early fetal life, the bladder is merely a conduit allowing urine to pass through freely into the amniotic cavity. As the striated external urethral sphincter evolves, the bladder acquires its reservoir and voiding functions. We characterized the myogenic and neurogenic contractions of the normal fetal porcine bladder from midterm until close to full-term gestation.MethodsContractile responses were measured in vitro using bladder strips from fetuses at 60 (N=23) and 100 days (N=21) of gestation. Spontaneous activity, and the responses to potassium chloride (KCl) solution, electrical field stimulation (EFS), and receptor activation were recorded. The smooth muscle content was evaluated histologically.ResultsHistological studies revealed that the fractional content of smooth muscle doubled between the two time points, and passive tension was adjusted to take that into account. Spontaneous activity was regular at 60 days, changing toward an irregular pattern at 100 days. Contractile force elicited by KCl and carbachol increased significantly with gestational age, while contractions to the purinergic agonist, α-ß-methylene adenosine 5'-triphosphate did not. The responses to EFS were almost completely blocked by atropine.ConclusionSpontaneous myogenic contractions become irregular and contractile responses to muscarinic receptor stimulation increase during gestation, as the bladder reservoir and voiding functions develop.

Mitral Regurgitation Severity and Left Ventricular Systolic Dimension Predict Survival in Young Cavalier King Charles Spaniels.

BACKGROUND: Development and progression of myxomatous mitral valve disease (MMVD) in dogs are difficult to predict. Identification at a young age of dogs at high risk of adverse outcome in the future is desirable. HYPOTHESIS/OBJECTIVES: To study the predictive value of selected clinical and echocardiographic characteristics associated with MMVD obtained at a young age for prediction of long-term cardiac and all-cause mortality in Cavalier King Charles Spaniels (CKCS). ANIMALS: 1125 privately owned CKCS. METHODS: A retrospective study including CKCS examined at the age of 1-3 years. Long-term outcome was assessed by telephone interview with owners. The value of variables for predicting mortality was investigated by Cox proportional hazard and Kaplan-Meier analyses. RESULTS: Presence of moderate to severe mitral regurgitation (MR) (hazard ratio (HR) = 3.03, 95% confidence interval (95% CI) = 1.48-6.23, P = 0.0025) even intermittent moderate to severe MR (HR = 2.23, 95% CI = 1.48-6.23, P = 0.039) on color flow Doppler echocardiography was significantly associated with increased hazard of cardiac death. An interaction between MR and sex was significant for all-cause mortality (P = 0.035), showing that males with moderate to severe MR had a higher all-cause mortality compared to males with no MR (HR = 2.38, 95% CI = 1.27-4.49, P = 0.0071), whereas no difference was found between female MR groups. The risk of cardiac (HR = 1.37, 95% CI = 1.14-1.63, P < 0.001) and all-cause (HR = 1.13, 95% CI = 1.02-1.24, P = 0.016) mortality increased with increasing left ventricular end-systolic internal dimension normalized for body weight (LVIDSN ). CONCLUSIONS AND CLINICAL IMPORTANCE: Moderate to severe MR, even if intermittent, and increased LVIDSN in dogs <3 years of age were associated with cardiac death later in life in CKCS.

Markers of Oxidative Stress in Dogs with Myxomatous Mitral Valve Disease are Influenced by Sex, Neuter Status, and Serum Cholesterol Concentration.

BACKGROUND: Cardiovascular disease has been associated with oxidative stress, which has been suggested to contribute to myocardial remodeling in human patients. Little is known about the relationship between myxomatous mitral valve disease (MMVD) and oxidative stress in dogs. OBJECTIVE: To determine whether clinical stage of MMVD is associated with changes in the plasma concentrations of certain markers of oxidative stress in clinically healthy dogs and dogs with MMVD. ANIMALS: Seventy five privately owned dogs: 59 cavalier King Charles Spaniels (CKCS) with different severities of MMVD and 16 dogs of different breeds with clinical signs of congestive heart failure (CHF) caused by MMVD. METHODS: Markers of oxidative stress including malondialdehyde (MDA), oxidized low-density lipoprotein (oxLDL), and vitamin E (α-tocopherol and γ-tocopherol) were measured in plasma and their association with clinical stage of MMVD was assessed by regression analyses. RESULTS: Plasma oxLDL concentration was significantly lower in female dogs compared with males (P = .01). Significantly higher plasma γ-tocopherol concentrations were found in neutered (P = .003) dogs. Vitamin E (α-tocopherol [P = .0004] and γ-tocopherol [P = .003]) was associated with body condition score (BCS), but the association disappeared when cholesterol was included in the analyses. All markers of oxidative stress (MDA, oxLDL, and vitamin E) were positively associated with serum cholesterol concentration (P ≤ .04), but none were associated with clinical stage of MMVD. CONCLUSIONS: In conclusion, markers of oxidative stress are associated with sex, BCS, neuter status, and cholesterol. The results cannot confirm a relationship between oxidative stress and clinical stage of the disease in dogs with MMVD.

Increased serum C-reactive protein concentrations in dogs with congestive heart failure due to myxomatous mitral valve disease.

Cardiovascular disease in humans and dogs is associated with mildly increased circulating concentrations of C-reactive protein (CRP). Few studies have evaluated associations between circulating CRP and canine myxomatous mitral valve disease (MMVD) and the results reported have been divergent. The aim of this study was to investigate whether serum concentrations of CRP, determined using a novel automated canine-specific high-sensitivity CRP assay (Gentian hsCRP), were associated with severity of MMVD and selected clinical variables in dogs. The study included 188 client-owned dogs with different severities of MMVD. Dogs were classified based on ACVIM consensus statement guidelines (group A, n = 58; group B1, n = 56; group B2, n = 38; group C, n = 36). Data were analysed using descriptive statistics and multiple regression analysis. Dogs with congestive heart failure (CHF; group C) had significantly higher CRP concentrations (median, 2.65 mg/L; quartile 1-quartile 3, 1.09-5.09) compared to dogs in groups A (median, 0.97 mg/L; quartile 1-quartile 3, <0.50-1.97; P = 0.001), B1 (median, 0.78 mg/L; quartile 1-quartile 3, <0.50-1.73, P <0.0001) and B2 (median, 0.60 mg/L; quartile 1-quartile 3, <0.50-1.23; P <0.0001). Other variables reflecting disease severity, including left atrial to aortic root ratio (P = 0.0002, adjusted r(2) = 0.07) and left ventricular end-diastolic diameter normalised for bodyweight (P = 0.0005, adjusted r(2) = 0.06), were positively associated with CRP concentration, but the association disappeared if dogs with CHF were excluded from analysis. In conclusion, slightly higher CRP concentrations were found in dogs with CHF whereas severity of asymptomatic MMVD showed no association with CRP concentrations.

Breeding Restrictions Decrease the Prevalence of Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniels over an 8- to 10-Year Period.

BACKGROUND: Cavalier King Charles Spaniels (CKCS) are predisposed to myxomatous mitral valve disease (MMVD). Studies have indicated a strong genetic background. OBJECTIVE: The aim of this study was to evaluate the effect of a breeding scheme involving auscultation and echocardiography. ANIMALS: In the Danish Kennel Club mandatory breeding scheme, 997 purebred CKCS were examined during the period 2002-2011. Each dog was evaluated 1-4 times with a total of 1,380 examinations. METHODS: Auscultation and echocardiography were performed to evaluate mitral regurgitation murmur severity and degree of mitral valve prolapse (MVP). The odds of having mitral regurgitation murmur or MVP > grade 1 in 2010-2011 compared to 2002-2003 were estimated using logistic regression analysis including age and sex as covariates. Odds were estimated for dogs that were products of the breeding scheme (defined as dogs with both parents approved by the breeding scheme before breeding) and non-products of the breeding scheme (defined as dogs with at least 1 parent with unknown cardiac status). RESULTS: In 2010-2011, the odds of having mitral regurgitation murmur were 0.27 if dogs were a product of the breeding scheme compared with dogs in 2002-2003, reflecting a 73% decreased risk (P < .0001). If non-products of the breeding scheme examined in 2010-2011 were compared with dogs in 2002-2003, no difference in odds was found (P = .49). CONCLUSION AND CLINICAL IMPORTANCE: A mandatory breeding scheme based on auscultation and echocardiography findings significantly decreased the prevalence of MMVD over the 8- to 10-year period. Such a breeding scheme therefore is recommended for CKCS.

Alpha-smooth muscle actin and serotonin receptors 2A and 2B in dogs with myxomatous mitral valve disease.

Canine Myxomatous mitral valve disease (MMVD) is an age-related disease. Serotonin (5-HT) is implicated in the pathogenesis as locally-produced or platelet-derived. Involvement of the 5-HT2A receptor (R) and 5-HT2BR in the induction of myxomatous-mediating valvular myofibroblasts (MF) has been suggested. In an age-matched population of dogs with non-clinical and clinical MMVD, the objectives were to investigate (1) gene expression of 5-HT2AR and 5-HT2BR, (2) protein expression and spatial relationship of 5-HT2AR, 5-HT2BR and MF in the mitral valve (MV) and the cardiac anterior papillary muscle (AP) and (3) serum 5-HT concentrations. Gene expression of 5-HT2BR was significantly higher in MV and AP among dogs with clinical MMVD. This was not found for 5-HT2BR protein expression, though association of 5-HT2BR with myxomatous pathology and co-localization of 5-HT2BR and MF in MV and AP support a functional relationship, perhaps perpetuation of clinical MMVD. 5-HT2AR-expression and serum 5-HT showed no differences between groups.

Serotonin markers show altered transcription levels in an experimental pig model of mitral regurgitation.

Serotonin (5-hydroxytryptamine, 5-HT) signalling is implicated in the pathogenesis of myxomatous mitral valve disease (MMVD) through 5-HT1B receptor (R), 5-HT2AR and 5-HT2BR-induced myxomatous pathology. Based on increased tryptophan hydroxylase-1 (TPH-1) and decreased serotonin re-uptake transporter (SERT) in MMVD-affected valves, increased valvular 5-HT synthesis and decreased clearance have been suggested. It remains unknown how haemodynamic changes associated with mitral regurgitation (MR) affect 5-HT markers in the mitral valve, myocardium and circulation. Twenty-eight pigs underwent surgically induced MR or sham-operation, resulting in three MR groups: control (CON, n = 12), mild MR (mMR, n = 10) and severe MR (sMR, n = 6). The gene expression levels of 5-HT1BR, 5-HT2AR, 5-HT2BR, SERT and TPH-1 were analysed using quantitative PCR (qPCR) in the mitral valve (MV), anterior papillary muscle (AP) and left ventricle (LV). MV 5-HT2BR was also analysed with immunohistochemistry (IHC) in relation to histological lesions and valvular myofibroblasts. All 5-HTR mRNAs were up-regulated in MV compared to AP and LV (P <0.01). In contrast, SERT and TPH-1 were up-regulated in AP and LV compared to MV (P <0.05). In MV, mRNA levels were increased for 5-HT2BR (P = 0.02) and decreased for SERT (P = 0.03) in sMR vs. CON. There were no group differences in 5-HT2BR staining (IHC) but co-localisation was found with α-SMA-positive cells in 91% of all valves and with 33% of histological lesions. In LV, 5-HT1BR mRNA levels were increased in sMR vs. CON (P = 0.01). In conclusion, these data suggest that MR may affect mRNA expression of valvular 5-HT2BR and SERT, and left ventricular 5-HT1BR in some pigs.

Matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs) and transforming growth factor-ß (TGF-ß) in advanced canine myxomatous mitral valve disease.

This study investigated mitral valve and myocardial protein and gene expression of matrix metalloproteinases (MMPs), their tissue inhibitors (TIMPs) and transforming growth factor-ß (TGF-ß) and plasma MMP and TGF-ß concentrations in age-matched dog groups euthanized due to either advanced myxomatous mitral valve disease (MMVD) or other reasons. Furthermore, echocardiographic data and lumen/area ratio were correlated with tissue and plasma levels of MMPs, TIMPs and TGF-ßs. Mitral valve and myocardial gene expression of MMP2, MMP14, TGF-ß1 and TGF-ß2 were increased and plasma MMP9 was decreased in advanced MMVD dogs. Myocardial gene expression of TIMP2 and TIMP3 were increased in advanced MMVD. All affected markers correlated to echocardiographic parameters. Significantly narrowed lumen/area ratio was associated with increased myocardial expression of MMP2, MMP14, TIMP2 and TIMP3. No differences in tissue protein expression were recorded. MMP2, MMP14, TIMP2, TIMP3, TGF-ß1 and TGF-ß2 appear to play a local role in the development of advanced MMVD.

Biopterin status in dogs with myxomatous mitral valve disease is associated with disease severity and cardiovascular risk factors.

BACKGROUND: Endothelial dysfunction (ED) has been suggested to be associated with myxomatous mitral valve disease (MMVD) in dogs. Tetrahydrobiopterin (BH4) is an important cofactor for production of the endothelium-derived vasodilator nitric oxide (NO). Under conditions of oxidative stress, BH4 is oxidized to the biologically inactive form dihydrobiopterin (BH2). Thus, plasma concentrations of BH2 and BH4 may reflect ED and oxidative stress. OBJECTIVE: To determine plasma concentrations of BH2 and BH4 in dogs with different degrees of MMVD. ANIMALS: Eighty-four privately owned dogs grouped according to ACVIM guidelines (37 healthy control dogs including 13 Beagles and 24 Cavalier King Charles Spaniels [CKCSs], 33 CKCSs with MMVD of differing severity including 18 CKCSs [group B1] and 15 CKCSs [group B2], and 14 dogs of different breeds with clinical signs of congestive heart failure [CHF] because of MMVD [group C]). METHODS: Dogs underwent clinical examination including echocardiography. Plasma concentrations of BH2 and BH4 were measured using high-performance liquid chromatography with fluorescence detection. RESULTS: Higher plasma BH4 and BH2 concentrations were found with dogs in CHF compared with all other groups (control, B1 and B2; P ≤ .001). Females had higher concentrations of BH4 and BH4/BH2 (P ≤ .0003). BH4/BH2 was found to decrease with age (P < .0001). Cardiovascular risk factors in humans such as passive smoking (P ≤ .01) and increased body weight (P ≤ .009) were associated with lower BH4 concentrations. CONCLUSIONS AND CLINICAL IMPORTANCE: Age, sex, body weight, passive smoking, and cardiac status are associated with plasma biopterin concentration in dogs. Additional studies should clarify the clinical implications of the findings.

Serotonin concentrations in platelets, plasma, mitral valve leaflet, and left ventricular myocardial tissue in dogs with myxomatous mitral valve disease.

HYPOTHESIS/OBJECTIVES: Altered serotonin (5-hydroxytryptamine, 5HT) signaling is postulated in development and progression of canine myxomatous mitral valve disease (MMVD). Little is known regarding platelet, plasma, valvular, or myocardial 5HT concentration ([5HT]) in affected dogs. We quantified [5HT] in platelet-rich plasma (PRP), platelet-poor plasma (PPP), mitral valve leaflets (MV), and left ventricular myocardium (LV). ANIMALS: Forty-five dogs comprised 4 plasma groups of Cavalier King Charles Spaniels (CKCS) or non-CKCS, either healthy (CON) or MMVD affected: CKCS CON (n = 12); non-CKCS CON (n = 8); CKCS MMVD (n = 14); non-CKCS MMVD (n = 11). Twenty-four dogs comprised 3 tissue groups: MMVD (n = 8); other-HD (heart disease) (n = 7); non-HD, extracardiac disease (n = 9). METHODS: High-performance liquid chromatography measured PRP, PPP, MV, and LV [5HT]. RESULTS: Platelet-rich plasma platelet [5HT] was greater in CKCS CON (1.83 femtograms/platelet [fg/plt]; range, 0.20-4.76; P = .002), CKCS MMVD (1.58 fg/plt; range, 0.70-4.03; P = .005), and non-CKCS MMVD (1.72 fg/plt; range, 0.85-4.44; P = .003) versus non-CKCS CON (0.92 fg/plt; range, 0.63-1.30). There was no group difference in PPP [5HT]. MV [5HT] was significantly higher in MMVD (32.4 ng/mg; range, 8.4-106.7) versus non-HD (3.6 ng/mg; range, 0-28.3; P = .01) and LV [5HT] was significantly higher in MMVD (11.9 ng/mg; range, 4.0-104.8) versus other-HD (0.9 ng/mg; range, 0-10.1; P = .011) and non-HD (2.5 ng/mg; range, 0-6.9; P = .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Platelet [5HT] was highest in healthy CKCS and both MMVD groups, but plasma [5HT] showed no group differences. Tissue [5HT] was highest in MV and LV of MMVD-affected dogs, suggesting altered 5HT signaling as a potential feature of MMVD. Interactions of platelet, valvular, and myocardial 5HT signaling warrant further investigation.

R-R interval variations influence the degree of mitral regurgitation in dogs with myxomatous mitral valve disease.

Mitral regurgitation (MR) due to myxomatous mitral valve disease (MMVD) is a frequent finding in Cavalier King Charles Spaniels (CKCSs). Sinus arrhythmia and atrial premature complexes leading to R-R interval variations occur in dogs. The aim of the study was to evaluate whether the duration of the R-R interval immediately influences the degree of MR assessed by echocardiography in dogs. Clinical examination including echocardiography was performed in 103 privately-owned dogs: 16 control Beagles, 70 CKCSs with different degree of MR and 17 dogs of different breeds with clinical signs of congestive heart failure due to MMVD. The severity of MR was evaluated in apical four-chamber view using colour Doppler flow mapping (maximum % of the left atrium area) and colour Doppler M-mode (duration in ms). The influence of the ratio between present and preceding R-R interval on MR severity was evaluated in 10 consecutive R-R intervals using a linear mixed model for repeated measurements. MR severity was increased when a short R-R interval was followed by a long R-R interval in CKCSs with different degrees of MR (P<0.005 when adjusted for multiple testing). The relationship was not significant in control dogs with minimal MR and in dogs with severe MR and clinical signs of heart failure. In conclusion, MR severity increases in long R-R intervals when these follow a short R-R interval in CKCSs with different degrees of MR due to asymptomatic MMVD. Thus, R-R interval variations may affect the echocardiographic grading of MR in CKCSs.

Holter monitoring of small breed dogs with advanced myxomatous mitral valve disease with and without a history of syncope.

BACKGROUND: Syncope is a transient loss of consciousness occasionally occurring in dogs with advanced myxomatous mitral valve disease (MMVD). OBJECTIVE: (1) To study ECG changes during syncopal episodes in dogs with advanced MMVD and (2) to compare the occurrence of arrhythmias and changes in heart rate variability (HRV) between dogs with advanced MMVD with and without a history of syncope. ANIMALS: Forty-three privately owned dogs (<15 kg) with advanced MMVD: 21 with and 22 without a history of syncope. METHODS: Prospective study with dogs recruited for an evaluation including history, physical examination, echocardiography, and arrhythmia and HRV analysis performed on 24-hour Holter recordings. RESULTS: A syncopal episode was observed during Holter monitoring in 4 dogs: 3 dogs had sinus rhythm and 1 dog had sinus arrest followed by escape rhythm. An arrhythmia variable representing sinus arrhythmia was significantly lower in dogs with a history of syncope than in those without (P = .008). Eight of 26 HRV variables were significantly different between dogs with and without a history of syncope. CONCLUSIONS AND CLINICAL IMPORTANCE: Compared with dogs without a history of syncope, dogs with advanced MMVD and a history of syncope did not have a higher occurrence of arrhythmias, but had less sinus arrhythmia, and had changes in HRV variables representing decreased overall HRV, decreased parasympathetic, and increased sympathetic modulation of heart rate.

Left ventricular twist and circumferential strain in dogs with myxomatous mitral valve disease.

BACKGROUND: During the cardiac cycle, the ventricle undergoes a twisting motion because of the oblique orientation of the left ventricular (LV) myofibers. This can be quantified by speckle-tracking echocardiography (STE). In mitral regurgitation (MR) in humans, the short axis deformation has been suggested as being pivotal to LV function. Decreased and delayed LV twist has been described in experimental MR, but has not been studied in myxomatous mitral valve disease (MMVD). HYPOTHESES: (1) Magnitude (CSt) and rate (CSRs) of systolic circumferential deformation decrease before the onset of congestive heart failure (CHF); (2) magnitude and rate of LV twist decrease, and onset of untwist is delayed, with increasing MMVD severity. ANIMALS: A total of 97 privately owned small- to medium-sized dogs. METHODS: Severity of MMVD was assessed by echocardiography and presence of clinical signs of CHF. Magnitude and rate of LV twist and circumferential deformation were evaluated by STE. RESULTS: Dogs with CHF receiving treatment had increased CSt, CSRs, early diastolic untwisting rate, and delayed onset of untwist compared to dogs with minimal MMVD and increased systolic twist compared to dogs with mild MMVD (all P < .01). CSt and time to onset of untwist increased with echocardiographic variables of MR severity (all P < .002). CSRs and several LV twist variables decreased with increasing systolic LV internal diameter (all P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: No STE-derived variable was decreased before onset of CHF. In dogs with CHF receiving treatment, the delayed onset of relaxation might indicate LV dysfunction and the hyperdynamic CSt and LV twist reflect compensatory mechanisms.

Cardiac troponin-I concentration, myocardial arteriosclerosis, and fibrosis in dogs with congestive heart failure because of myxomatous mitral valve disease.

BACKGROUND: Few previous studies have investigated the association between biomarkers and cardiac disease findings in dogs with naturally occurring myxomatous mitral valve disease (MMVD). AIM: To investigate if histopathological changes at necropsy could be reflected by in vivo circulating concentrations of cTnI and aldosterone, and renin activity, in dogs with naturally occurring congestive heart failure because of MMVD. ANIMALS: Fifty privately owned dogs with MMVD and heart failure. METHODS: Longitudinal Study. Dogs were prospectively recruited and examined by clinical and echocardiographical examination twice yearly until time of death. Blood was stored for batched analysis of concentrations of cTnI and aldosterone, and renin activity. All dogs underwent a standardized necropsy protocol. RESULTS: cTnI were associated with echocardiographic left ventricular end-diastolic dimension (P < .0001) and proximal isovolumetric surface area radius (P < .004). Furthermore, in vivo cTnI concentrations reflected postmortem findings of global myocardial fibrosis (P < .001), fibrosis in the papillary muscles (P < .001), and degree of arterial luminal narrowing (P < .001) Aldosterone or renin activity did not reflect any of the cardiac disease variables investigated. CONCLUSION AND CLINICAL IMPORTANCE: Cardiac fibrosis and arteriosclerosis in dogs with MMVD are reflected by circulating cTnI concentration, but not by aldosterone concentration or renin activity. Cardiac troponin I could be a valuable biomarker for myocardial fibrosis in dogs with chronic cardiac diseases.

Radial and longitudinal strain and strain rate assessed by speckle-tracking echocardiography in dogs with myxomatous mitral valve disease.

BACKGROUND: Assessment of left ventricular (LV) function using conventional echocardiographic methods is difficult in mitral regurgitation (MR) owing to altered hemodynamic loading conditions. Newer methods such as speckle-tracking echocardiography (STE) provide assessment of LV strain (St) and strain rates (SR). HYPOTHESES: Global St and SR are 1) decreased in dogs with clinical signs of congestive heart failure (CHF) due to myxomatous mitral valve disease (MMVD) compared with clinically healthy dogs, and are 2) associated with conventional echocardiographic indices of MMVD severity. ANIMALS: The study subjects were 93 privately owned dogs with different MMVD severities. METHODS: Prospectively recruited dogs were grouped according to MMVD severity based on echocardiographic evaluation of MR and presence of clinical signs. Global radial and longitudinal St, SR, and indices of LV dyssynchrony were assessed. RESULTS: On group-wise comparisons, dogs with CHF had increased global longitudinal St, global longitudinal and radial SR in systole (SRs), and early diastole (SRe) compared with dogs with no or minimal MR (all P < .04). On multiple regression analyses, these global STE variables increased with degree of MR, but associations with left atrial-to-aortic root ratio (LA/Ao) were best described by second-order polynomial equations. Thus, curvilinear relationships were found for LA/Ao and longitudinal St, SRs, and SRe (all P < .002) and radial St and SRe (all P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Assessed by STE, LV function appeared to be augmented in moderate-to-severe disease. However, at CHF stages with greatly enlarged atria, a decrease to levels comparable to dogs with no or minimal MR was observed.

Accuracy of cryptorchidism diagnoses and corrective surgical treatment registration in the Danish National Patient Registry.

PURPOSE: In recent years several Danish studies of the etiology, time trends and long-term health consequences of cryptorchidism have relied on diagnoses and surgical treatments registered in the National Patient Registry. We evaluated the diagnostic accuracy of these registry data. MATERIALS AND METHODS: According to the Danish National Patient Registry, 16,168 males were diagnosed with cryptorchidism and 9,244 surgical treatments for cryptorchidism were performed between January 1, 1995 and October 10, 2009. We randomly selected 500 diagnosed cases, of which 284 had been managed surgically. We requested the medical records from the departments making the diagnoses and performing the surgery. RESULTS: We successfully retrieved medical records for 452 diagnosed cases (90%) and 249 operations (88%). Overall positive predictive value of a registry diagnosis of cryptorchidism was 80% (95% CI 77-84) using the testicular position described by the physician performing the clinical examination as the gold standard. Similarly the positive predictive value of the surgical treatment registration was 99% (95% CI 98-100) using the type of procedure performed. CONCLUSIONS: The data on cryptorchidism in the Danish National Patient Registry are quite accurate. In etiological research the limited misclassification will in most cases only slightly attenuate estimates of the true relative association. Thus, the registry has the potential to serve as a valuable research tool, although caution should be exercised when studying time trends or geographical differences.

Heart rate, heart rate variability, and arrhythmias in dogs with myxomatous mitral valve disease.

BACKGROUND: Autonomic modulation of heart rhythm is thought to influence the pathophysiology of myxomatous mitral valve disease (MMVD). HYPOTHESES: (1) Holter-derived variables reflecting autonomic modulation of heart rhythm change with MMVD severity in Cavalier King Charles Spaniels (CKCS); (2) Holter-derived variables can identify MMVD severity in CKCS; and (3) Holter-derived variables in CKCS in congestive heart failure (CHF) secondary to MMVD differ from those in dogs of other breeds in CHF. ANIMALS: Ninety privately owned dogs: 70 CKCS with variable MMVD severity and 20 non-CKCS in CHF secondary to MMVD. METHODS: Dogs were prospectively recruited and divided into 5 MMVD severity groups based on history, breed, and physical and echocardiographic examination findings. Holter-derived variables included heart rate variability (HRV), heart rate (HR), and arrhythmia evaluated from 24-hour Holter recordings. RESULTS: In CKCS, 18 of 26 HRV (all P < .0002) and 3 of 9 arrhythmia (all P < .0004) variables decreased with increasing MMVD, whereas minimum and mean HR (all P < .0001) increased with increasing MMVD severity. An arrhythmia variable representing sinus arrhythmia ("premature normals") (P < .0001) and the HRV variable triangular index (TI) (P < .0001) could distinguish CKCS with moderate or severe mitral regurgitation from CKCS in CHF in specific intervals. Among dogs in CHF, Holter-derived variables did not differ among breeds. CONCLUSIONS AND CLINICAL IMPORTANCE: In CKCS, Holter-derived variables changed with MMVD severity. "Premature normals" and TI showed diagnostic potential. Breed differences were not seen among dogs in CHF secondary to MMVD.