Katja Höglund

Predictive value of natriuretic peptides in dogs with mitral valve disease

Natriuretic peptides are useful in diagnosing heart failure in dogs. However, their usefulness in detecting early stages of myxomatous mitral valve disease (MMVD) has been debated. This study evaluated N-terminal (NT) fragment pro-atrial natriuretic peptide (NT-proANP) and NT-pro-brain natriuretic peptide (NT-proBNP) in 39 Cavalier King Charles Spaniels (CKCS) with pre-clinical mitral valve regurgitation (MR), sixteen dogs with clinical signs of heart failure (HF) and thirteen healthy control dogs. Twenty seven CKCS and ten control dogs were re-examined 4 years after the initial examination and the status of the dogs 5 years after the initial examination was determined by telephone calls to the owner. All dogs were evaluated by clinical examination and echocardiography. CKCS with severe MR had higher NT-proANP and NT-proBNP compared to controls and CKCS with less severe MR. Dogs with clinical signs of HF had markedly elevated NT-proANP and NT-proBNP. Plasma concentrations of the natriuretic peptides measured at re-examination could predict progression in regurgitant jet size.

An update on treatment and prognostic indicators in canine myxomatous mitral valve disease

Mitral regurgitation caused by myxomatous mitral valve disease is the most common cause for congestive heart failure and cardiac-related mortality in dogs. Typically, it takes several years for the disease to progress from mild, clinically silent myxomatous mitral valve disease to severe disease with signs of congestive heart failure. A proportion of dogs will never progress into congestive heart failure before they die from other causes or old age. Some variables have been shown to be predictive of onset of congestive heart failure and they might be useful to identify dogs that need more frequent monitoring and eventually treatment. Results from several controlled clinical trials are available concerning medical treatment of dogs with myxomatous mitral valve disease with or without congestive heart failure. These trials provide estimates of treatment effects and also allow identification of other variables with prognostic value for the outcome after the onset of congestive heart failure. Use of prognostic variables together with qualitative and quantitative results from clinical drug trials may aid the clinician and owner to plan and decide on optimal management of the myxomatous mitral valve disease dog. The purpose of this article is to review the current knowledge of prognostic variables and therapy for this common condition in dogs.

Identification of 2 Loci Associated with Development of Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniels

Myxomatous mitral valve disease (MMVD) is the most common heart disease in dogs. It is characterized by chronic progressive degenerative lesions of the mitral valve. The valve leaflets become thickened and prolapse into the left atrium resulting in mitral regurgitation (MR). MMVD is most prevalent in small to medium sized dog breeds, Cavalier King Charles Spaniels (CKCS) in particular. The onset of MMVD is highly age dependent, and at the age of 10 years, nearly all CKCS are affected. The incidence of a similar disease in humans-mitral valve prolapse-is 1-5%. By defining CKCSs with an early onset of MMVD as cases and old dogs with no or mild signs of MMVD as controls, we conducted a genome-wide association study (GWAS) to identify loci associated with development of MMVD. We have identified a 1.58 Mb region on CFA13 (P(genome) = 4.0 × 10(-5)) and a 1.68 Mb region on CFA14 (P(genome) = 7.9 × 10(-4)) associated with development of MMVD. This confirms the power of using the dog as a model to uncover potential candidate regions involved in the molecular mechanisms behind complex traits.

Tissue Doppler and Strain Imaging in Dogs with Myxomatous Mitral Valve Disease in Different Stages of Congestive Heart Failure

BACKGROUND Tissue Doppler imaging (TDI) including strain and strain rate (SR) assess systolic and diastolic myocardial function. HYPOTHESIS TDI, strain, and SR variables of the left ventricle (LV) and the interventricular septum (IVS) differ significantly between dogs with myxomatous mitral valve disease (MMVD) with and without congestive heart failure (CHF). ANIMALS Sixty-one dogs with MMVD with and without CHF. Ten healthy control dogs. METHODS Prospective observational study. RESULTS Radial motion: None of the systolic variables were altered and 3 of the diastolic velocities were significantly increased in dogs with CHF compared with dogs without CHF and control dogs. Longitudinal motion: 2 systolic velocities and 3 diastolic velocities were significantly increased in dogs with CHF compared with dogs without CHF and control dogs. Difference in systolic velocity time-to-peak between LV and IVS was significantly increased in dogs with MMVD with and without CHF compared with control dogs. In total, 11 (23%) of 48 TDI and strain variables differed significantly between groups. Left atrial to aortic ratio was positively correlated to early diastolic velocities, percentage increase in left ventricular internal diameter in systole was positively correlated to systolic and diastolic velocities, and mitral E wave to peak early diastolic velocity in the LV basal segment (E/Em) was positively correlated to radial strain and SR. CONCLUSIONS AND CLINICAL IMPORTANCE Few TDI and strain variables were changed in dogs with MMVD with and without CHF. Intraventricular dyssynchrony may be an early sign of MMVD or may be an age-related finding.

Cardiac troponin I and the occurrence of cardiac arrhythmias in horses with experimentally induced endotoxaemia.

The aim of this study was to determine whether experimentally-induced endotoxaemia induced elevations in plasma cardiac troponin I (cTnI) concentrations in horses and how this might affect the incidence of cardiac arrhythmias. Eight Standardbred horses received an intravenous continuous rate infusion of endotoxin (total dose 500 ng/kg) for 6 h while being monitored using electrocardiography (ECG). Blood samples were collected before the start of the endotoxin infusion, every 60 min during the infusion, then 1, 2, 3, 8, 10 and 24 h post-infusion, and analysed for cTnI concentrations. One horse was excluded from the study owing to a high initial cTnI concentration. Endotoxin infusion induced an increase in cTnI concentrations in all horses, reaching mean peak concentration of 0.135±0.094 μg/L by 1 h post-infusion. The cTnI concentrations then decreased and were no longer significantly different from pre-infusion concentrations at 6, 10 and 24 h post-infusion. The number of ventricular events was generally low during the infusion period, but increased during the first 3 h post-infusion in 6/7 horses. In conclusion, elevated cTnI concentrations could be detected early after an endotoxaemic insult using an ultrasensitive cTnI assay, with peak cTnI concentrations preceding the occurrence of ventricular events on ECG.

Assessment of global and regional left ventricular volume and shape by real-time 3-dimensional echocardiography in dogs with myxomatous mitral valve disease.

BACKGROUND Left ventricular (LV) remodeling occurs in response to chronic volume overload. Real-time 3-dimensional (RT3D) echocardiography offers new modalities for LV assessment. OBJECTIVE To investigate LV changes in shape and volume in response to different severities of naturally acquired myxomatous mitral valve disease (MMVD) in dogs by RT3D echocardiography. ANIMALS Sixty-five client-owned dogs. METHODS Prospectively recruited dogs were classified by standard echocardiography into healthy, mild, moderate, and severe MMVD groups. Endocardial border tracking of LV RT3D dataset was performed, from which global and regional (automatically acquired basal, mid, and apical segments based on LV long-axis length) end-diastolic (EDV) and end-systolic volumes (ESV), LV long-axis length, and sphericity index were obtained. RESULTS Global and regional EDV and ESV (indexed to body weight) were most prominently increased in dogs with severe MMVD. All 3 regional LV segments contributed to increased global EDV and ESV with increasing MMVD severity, but mid-EDV contributed the most to the global EDV increase. Furthermore, LV long-axis length and LV sphericity index increased with increasing MMVD severity. Basal and apical EDV segments displayed the strongest association with sphericity index (P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE The most prominent LV volume expansion was found in dogs with severe MMVD. Increased EDV, primarily in the mid-segment, leads to rounding of LV apical and basal segments in response to increasing MMVD severity. Assessment of LV volume and shape potentially could allow early detection of dogs at risk for rapid progression into congestive heart failure.

Blood Pressure, Heart Rate, and Urinary Catecholamines in Healthy Dogs Subjected to Different Clinical Settings

BACKGROUND Correct interpretation of blood pressure (BP) and heart rate (HR) recordings is important in a clinical environment, but little is known about effects of stress on BP and HR responses of dogs to different clinical settings. OBJECTIVE To investigate BP and HR responses in different clinical settings in dogs of 3 breeds, and to relate findings to urinary catecholamine concentrations measured by ELISA assays previously validated for use in human plasma and urine, after validation for use in dogs. ANIMALS Client-owned healthy dogs; 41 Labrador Retrievers, 33 Cavalier King Charles Spaniels (CKCS), and 15 Dachshunds. METHODS Prospective observational study. BP and HR were measured in 4 clinical settings with or without veterinarian and owner present. Urine samples were taken before and after examination. ELISA assays were validated for canine urine, and epinephrine/creatinine and norepinephrine/creatinine ratios were analyzed. RESULTS BP and HR were higher when measured by veterinarian alone than when owner was present (P < .020). Urinary catecholamine/creatinine ratios were higher after examination, compared with before, in all dogs (P < .0001). Labrador Retrievers had lower diastolic BP than Dachshunds in 2 settings (P ≤ .041), lower HR than CKCSs in 3 settings (all P < .0001), and lower catecholamine/creatinine ratios after examination than both other breeds (P ≤ .035). The in-house validation showed mean spiked recovery of 96.5% for epinephrine and 83.8% for norepinephrine. CONCLUSIONS AND CLINICAL IMPORTANCE BP and HR responses were related to breed as well as clinical setting. Breed differences were detected in urinary catecholamine/creatinine ratios. Further studies on breed differences are warranted.

Use of signal analysis of heart sounds and murmurs to assess severity of mitral valve regurgitation attributable to myxomatous mitral valve disease in dogs.

OBJECTIVE To investigate use of signal analysis of heart sounds and murmurs in assessing severity of mitral valve regurgitation (mitral regurgitation [MR]) in dogs with myxomatous mitral valve disease (MMVD). ANIMALS 77 client-owned dogs. PROCEDURES Cardiac sounds were recorded from dogs evaluated by use of auscultatory and echocardiographic classification systems. Signal analysis techniques were developed to extract 7 sound variables (first frequency peak, murmur energy ratio, murmur duration > 200 Hz, sample entropy and first minimum of the auto mutual information function of the murmurs, and energy ratios of the first heart sound [S1] and second heart sound [S2]). RESULTS Significant associations were detected between severity of MR and all sound variables, except the energy ratio of S1. An increase in severity of MR resulted in greater contribution of higher frequencies, increased signal irregularity, and decreased energy ratio of S2. The optimal combination of variables for distinguishing dogs with high-intensity murmurs from other dogs was energy ratio of S2 and murmur duration > 200 Hz (sensitivity, 79%; specificity, 71%) by use of the auscultatory classification. By use of the echocardiographic classification, corresponding variables were auto mutual information, first frequency peak, and energy ratio of S2 (sensitivity, 88%; specificity, 82%). CONCLUSIONS AND CLINICAL RELEVANCE Most of the investigated sound variables were significantly associated with severity of MR, which indicated a powerful diagnostic potential for monitoring MMVD. Signal analysis techniques could be valuable for clinicians when performing risk assessment or determining whether special care and more extensive examinations are required.

Serum serotonin concentration is associated with severity of myxomatous mitral valve disease in dogs.

BACKGROUND The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has recently been suggested to play a role in the development of naturally acquired myxomatous mitral valve disease (MMVD) in dogs. AIM To investigate the association between serum 5-HT concentration and MMVD severity in dogs, and to assess potential associations between serum 5-HT concentrations and dog characteristics, echocardiographic variables, heart rate, systolic blood pressure, presence of macrothrombocytosis, and plateletcrit. ANIMALS A total of 120 client-owned dogs. MATERIAL AND METHODS Dogs were prospectively recruited and were classified by standard echocardiography into healthy (dogs of breeds predisposed to MMVD, but without echocardiographic evidence of the disease), mild, moderate, or severe MMVD groups. Serum 5-HT concentrations were analyzed using an ELISA. RESULTS Dogs with severe MMVD had lower serum 5-HT concentrations than healthy dogs (P = .0025) and dogs with mild MMVD (P = .0011). Unilinear and multiple regression analyses showed that serum 5-HT concentrations decreased with increasing left atrial to aortic root ratio (LA/Ao), were higher in Cavalier King Charles Spaniel (CKCS) dogs compared to dogs of other breeds, and were higher in female dogs than in male dogs. The LA/Ao was the variable most strongly associated with serum 5-HT concentration. CONCLUSIONS AND CLINICAL IMPORTANCE The finding of higher serum 5-HT concentrations in dogs of breeds predisposed to the early onset of MMVD (CKCS) and dogs with mild MMVD suggests that alterations in 5-HT signaling might play a role in progression of early stages of MMVD.

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), Simpsons 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.