Holter monitoring in 36 dogs with myxomatous mitral valve disease

Objective Describe the presence of arrhythmias in dogs with myxomatous mitral valve disease (MMVD) and the potential association with class of heart failure and left atrial enlargement. Compare the standard electrocardiogram (ECG) with Holter monitoring for assessing heart rate (HR). Experimental procedure The study group of 36 dogs weighing less than 20 kg was divided into MMVD and no clinical signs (preclinical) or MMVD and clinical signs (clinical). A standard echocardiogram, ECG and 24-h Holter recording were obtained in all dogs. Results Minimum and mean Holter HRs were higher in the clinical group than in the preclinical group. Clinical dogs had more ventricular arrhythmias than preclinical dogs. An enlarged left atrium was associated with the presence of more supraventricular arrhythmias. Conclusions Arrhythmias are a common finding in dogs with MMVD and Holter monitoring is a reliable tool for both HR monitoring and diagnosis.     

Dogs with heart diseases causing turbulent high-velocity blood flow have changes in platelet function and von Willebrand factor multimer distribution

The purpose of this prospective study was to investigate platelet function using in vitro tests based on both high and low shear rates and von Willebrand factor (vWf) multimeric composition in dogs with cardiac disease and turbulent high-velocity blood flow. Client-owned asymptomatic, untreated dogs were divided into 4 groups: 14 Cavalier King Charles Spaniels (Cavaliers) with mitral valve prolapse (MVP) and no or minimal mitral regurgitation (MR), 17 Cavaliers with MVP and moderate to severe MR, 14 control dogs, and 10 dogs with subaortic stenosis (SAS). Clinical examinations and echocardiography were performed in all dogs. PFA100 closure times (the ability of platelets to occlude a hole in a membrane at high shear rates), platelet activation markers (plasma thromboxane B2 concentration, platelet surface P-selectin expression), platelet aggregation (in whole blood and platelet-rich plasma with 3 different agonists), and vWf multimers were analyzed. Cavaliers with moderate to severe MR and dogs with SAS had longer closure times and a lower percentage of the largest vWf multimers than did controls. Maximal aggregation responses were unchanged in dogs with SAS but enhanced in Cavaliers with MVP (regardless of MR status) compared with control dogs. No significant difference in platelet activation markers was found among groups. The data suggest that a form of platelet dysfunction detected at high shear rates was present in dogs with MR and SAS, possibly associated with a qualitative vWf defect. Aggregation results suggest increased platelet reactivity in Cavaliers, but the platelets did not appear to circulate in a preactivated state in either disease.     

Circulating concentrations of insulin-like growth factor-1 in dogs with naturally occurring mitral regurgitation

Insulin-like growth factor-1 (IGF-1), which mediates most effects of growth hormone, has effects on cardiac mass and function, and plays an important role in the regulation of vascular tone. In humans, an inverse relationship between degree of heart failure (HF) and circulating IGF-1 concentrations has been found in several studies. In dogs with HF, few studies have focused on IGF-1. We examined circulating IGF-1 concentrations in dogs with mitral regurgitation (MR) caused by myxomatous mitral valve disease. Study 1 included 88 Cavalier King Charles Spaniels (CKCSs) with a broad range of asymptomatic MR (median serum IGF-1: 76.7 microg/L; 25-75 percentile, 59.8-104.9 microg/L). As expected, standard body weight and percentage under- or overweight correlated directly with IGF-1. MR (assessed in 4 different ways) did not correlate with IGF-1. In study 2, 28 dogs with severe MR and stable, treated congestive HF had similar serum IGF-1 concentrations (median, 100.8 g/L; 25-75 percentile, 74.9-156.5 microg/L) as 11 control dogs (79.6 microg/L; 25-75 percentile, 64.1-187.4 microg/L; P = .84). In study 3, the plasma IGF-1 concentration of 15 untreated CKCSs with severe MR was 16.4 +/- 24.2 microg/L lower (P = .02) at the examination when decompensated HF had developed (80.8 +/- 30.9 microg/L) than at a visit 1-12 months earlier (97.2 +/- 39.8 microg/L), possibly in part due to an altered state of nutrition. The studies document that circulating IGF-1 concentrations are not altered before development of congestive HF in dogs with naturally occurring MR, but decrease by approximately 20% with the development of untreated HE In treated HF, circulating IGF-1 concentrations apparently return to within the reference range.     

Pulmonary Hypertension Induced in Dogs by Hypoxia at Different High-Altitude Levels

Chronic natural hypoxia at 2300 m altitude induces mild pulmonary hypertension (PH) in healthy dogs. The influence of more severe hypoxia on the same group of dogs was evaluated by re-examining such dogs at 3500 m, after they had regularly exercised at this altitude level for half a year. Despite severe hypoxaemia at 3500 m (P _aO₂ 52±5 mmHg), none of the dogs developed erythrocytosis, and their PCV at 3500 m (48%±4%) did not differ from that at 2300 m (49%±4%). There was a tendency towards an elevated systemic BP, with a significant increase in diastolic BP (105±13 mmHg at 3500 m versus 98±17 at 2300 m). Tricuspid regurgitation (TR) was detected in 7 dogs at 3500 m compared to 8 dogs at 2300 m. The mean TR V _max was significantly higher at 3500 m, and all 7 dogs had systolic PH at 3500 m (33.6–54.8 mmHg), when PH was defined as TR V _max 2.8 m/s, i.e. a peak pressure gradient >30 mmHg. Hence, in dogs, increasing altitude and the concomitant hypoxia result in a progressively more pronounced PH and an elevated systemic BP. Intermittent severe hypoxaemia of around 50 mmHg may not cause erythrocytosis in healthy dogs, even over a prolonged period.     

Influence of combined angiotensin-converting enzyme inhibitors and spironolactone on serum K, Mg, and Na concentrations in small dogs with degenerative mitral valve disease

ObjectiveTo determine if the administration of an angiotensin-converting enzyme inhibitor (ACEI) plus spironolactone caused hyperkalemia, hypermagnesemia, or hyponatremia in elderly small dogs with degenerative mitral valve disease (MVD).BackgroundACEIs and spironolactone can increase serum potassium and magnesium concentrations and lower serum sodium concentrations. It has been recommended to either not combine these drugs or to do so with caution.Animals, material and methodsFifty client-owned dogs with MVD, left atrial dilation, and without congestive heart failure or azotemia were evaluated retrospectively. Baseline data sets, followed by 1–9 (mean = 2.66) data sets, comprised of serum urea nitrogen (SUN), creatinine, sodium, potassium, and magnesium concentrations, were tabulated. Each dog received an ACEI plus spironolactone for a mean of 23.8 ± 26.6 weeks (range: 2–150) and a median of 15 weeks. No cardiac drugs other than an ACEI and spironolactone were administered during the study period.ResultsThere were no significant differences between baseline and follow-up serum sodium or potassium concentrations. Serum magnesium concentrations increased significantly (p = 0.02) with time >20 weeks compared to baseline.ConclusionsThe combination of an ACEI and spironolactone results in no significant difference between baseline and follow-up serum sodium or potassium concentrations. Although serum magnesium concentrations may increase significantly with time >20 weeks compared to baseline concentrations, hypermagnesemia appears to be rare, mild, and unlikely to be of clinical importance. The combination of an ACEI and spironolactone is safe in elderly small dogs with MVD with normal SUN and creatinine concentrations.     

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.     

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.     

Pharmacokinetics of nicorandil in dogs with mild mitral regurgitation

The aim of this study was to examine the pharmacokinetics of nicorandil, a hybrid of an adenosine triphosphate-sensitive potassium channel opener and a nitrate, and to estimate its clinical doses in dogs with mild mitral valve regurgitation (MR). Nicorandil (0.1, 0.3, and 1.0 mg/kg) was administered orally to normal dogs and those with experimentally-induced MR, and its plasma concentrations were analyzed using high-performance liquid chromatography. Plasma concentrations increased dose-dependently after the administration of nicorandil, and were not different between normal dogs and those with MR. Similar to the effective plasma values obtained in cardiac disease in humans, the findings of this pharmacokinetic study may indicate that a dose of 0.3-1.0 mg/kg has the same effectiveness in dogs with cardiac dysfunction.     

Decreased systolic function and inadequate hypertrophy in large and small breed dogs with chronic mitral valve insufficiency

BACKGROUND: Systolic dysfunction associated with chronic mitral valve insufficiency (CMVI) has been demonstrated in experimental animal models and large breed (LB) dogs but has been reported as an uncommon finding in small breed (SB) dogs with naturally occurring disease. It has been suggested the myocardial failure could be, in part, because of an insufficient increase in left ventricular mass. HYPOTHESIS: To test if SB and LB dogs with CMVI and moderate heart failure have systolic dysfunction and if they have adequate eccentric hypertrophy. ANIMALS: Data from 38 SB and 18 LB dogs affected with CMVI were compared retrospectively with results from 2 groups of normal dogs (17 SB and 32 LB). METHODS: Systolic function was investigated echocardiographically by using percentage fractional shortening (FS), the ratio between observed and expected end-systolic diameter (ESD/ESDe), and end-systolic volume index (ESVI). Left ventricular hypertrophy was estimated by using the ratio between the thickness of the left ventricular free wall and the radius in diastole (h/R). RESULTS: Both affected SB and LB dogs had a significantly increased FS and ESVI (FS% SB 45.6 + 8.04 versus 40.06 + 8.9, P < .05; FS% LB 33.64 + 8.61 versus 27.3 + 7.3 P < .05; ESVI SB 30.0 +/- 2.3 mL/m2 versus 21.18 +/- 13.9 mL/m2, P < .05; ESVI LB 83.22 +/- 43.84 mL/m2 versus 36.43 +/- 13.30 mL/m2 versus P < .001). The h/R in affected animals was decreased (0.53 +/- 0.11 versus 0.41 +/- 0.12, P < .05 SB; 0.47 +/- 0.11 versus 0.38 +/- 0.09, P < .05, LB). CONCLUSIONS AND CLINICAL IMPORTANCE: Data from this study indicate that dogs with moderate heart failure caused by CMVI have systolic dysfunction. Inadequate hypertrophy of the left ventricle may be, in part, responsible for this finding.