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.

Longitudinal analysis of quality of life, clinical, radiographic, echocardiographic, and laboratory variables in dogs with myxomatous mitral valve disease receiving pimobendan or benazepril: the QUEST study.

BACKGROUND: Myxomatous mitral valve disease (MMVD) is an important cause of morbidity and mortality in dogs. OBJECTIVES: To compare, throughout the period of follow-up of dogs that had not yet reached the primary endpoint, the longitudinal effects of pimobendan versus benazepril hydrochloride treatment on quality-of-life (QoL) variables, concomitant congestive heart failure (CHF) treatment, and other outcome variables in dogs suffering from CHF secondary to MMVD. ANIMALS: A total of 260 dogs in CHF because of MMVD. METHODS: A prospective single-blinded study with dogs randomized to receive pimobendan (0.4-0.6 mg/kg/day) or benazepril hydrochloride (0.25-1.0 mg/kg/day). Differences in outcome variables and time to intensification of CHF treatment were compared. RESULTS: A total of 124 dogs were randomized to pimobendan and 128 to benazepril. No difference was found between groups in QoL variables during the trial. Time from inclusion to 1st intensification of CHF treatment was longer in the pimobendan group (pimobendan 98 days, IQR 30-276 days versus benazepril 59 days, IQR 11-121 days; P = .0005). Postinclusion, dogs in the pimobendan group had smaller heart size based on VHS score (P = .013) and left ventricular diastolic (P = .035) and systolic (P = .0044) dimensions, higher body temperature (P = .030), serum sodium (P = .0027), and total protein (P = .0003) concentrations, and packed cell volume (P = .030). Incidence of arrhythmias was similar in treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan versus benazepril resulted in similar QoL during the study, but conferred increased time before intensification of CHF treatment. Pimobendan treatment resulted in smaller heart size, higher body temperature, and less retention of free water.

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.

A prospective study of systolic ejection murmurs and left ventricular outflow tract in boxers.

OBJECTIVES: To investigate the prevalence and progression of murmurs and the development of the left ventricular outflow tract (LVOT) and flow velocities in the great arteries in boxer puppies through adolescence until three years of age. METHODS: Nineteen boxer puppies with or without a low-intensity murmur, but without evidence of congenital heart disease, were studied prospectively. Examinations were carried out at 7 weeks, 3, 4, 6, 9, 12 and 36 months of age by cardiac auscultation and Doppler echocardiography. RESULTS: Presence and intensity of heart murmurs varied in the same dog and between dogs, but flow velocities did not change. Estimated effective orifice diameter (EOD) and indexed EOD was significantly narrower than measured subvalvular and valvular diameters. CLINICAL SIGNIFICANCE: The variability in presence and intensity of low-intensity ejection murmurs is high during growth in boxers.

Plasma aldosterone concentration and cardiovascular response to low sodium intake in horses in training.

REASON FOR PERFORMING THE STUDY: Horses in training lose large amounts of sodium but little is known about the cardiovascular response to low sodium intake. OBJECTIVES: To investigate the effect of low sodium intake on plasma aldosterone (pAldo) concentrations and the cardiovascular system of athletic horses, and to identify markers of low sodium intake. METHODS: Seven Standardbred geldings in training (trained twice a week) were randomly offered a standardised diet supplemented (NaS, 58 mg Na/kg bwt) and not supplemented (NaN, 3 mg Na/kg bwt) with NaCl for 5 weeks in a changeover design. Blood samples were taken once a week and in Week 5, before and following an exercise test until 22.30 h and analysed for blood sodium (bNa), total plasma protein (TPP), pAldo, troponin I and packed cell volume (PCV). Blood pressure (BP) was measured and pulse wave recorded at rest with high definition oscillometric-technique (HDO). ECG and echocardiography were recorded. Water intake was measured before and on the day of exercise and voluntary saline intake was measured for 2 days after each period. Faecal samples were taken weekly and analysed for sodium and potassium content. RESULTS: The pAldo and the PCV was higher in NaN compared to NaS. There were no differences between diets in BP, ECG, plasma troponin I and echocardiogram but HDO pulse amplitude tended to be smaller on diet NaN. Water intake was lower on diet NaN and saline intake higher. The response to exercise in bNa, pAldo, PCV and TPP was different on the 2 diets. Faecal potassium/sodium ratio was higher on NaN than on NaS. CONCLUSION: This study shows that 5 weeks of low sodium intake increased plasma aldosterone concentration and PCV but no alterations in heart function was observed. Faecal potassium/sodium ratio could be used to assess sodium status in horses.

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.

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.

Effect of pimobendan or benazepril hydrochloride on survival times in dogs with congestive heart failure caused by naturally occurring myxomatous mitral valve disease: the QUEST study.

BACKGROUND: Myxomatous mitral valve disease (MMVD) continues to be an important cause of morbidity and mortality in geriatric dogs despite conventional therapy. HYPOTHESIS: Pimobendan in addition to conventional therapy will extend time to sudden cardiac death, euthanasia for cardiac reasons, or treatment failure when compared with conventional therapy plus benazepril in dogs with congestive heart failure (CHF) attributable to MMVD. ANIMALS: Two hundred and sixty client-owned dogs in CHF caused by MMVD were recruited from 28 centers in Europe, Canada, and Australia. METHODS: A prospective single-blinded study with dogs randomized to PO receive pimobendan (0.4-0.6 mg/kg/d) or benazepril hydrochloride (0.25-1.0 mg/kg/d). The primary endpoint was a composite of cardiac death, euthanized for heart failure, or treatment failure. RESULTS: Eight dogs were excluded from analysis. One hundred and twenty-four dogs were randomized to pimobendan and 128 to benazepril. One hundred and ninety dogs reached the primary endpoint; the median time was 188 days (267 days for pimobendan, 140 days for benazepril hazard ratio = 0.688, 95% confidence limits [CL]=0.516-0.916, P= .0099). The benefit of pimobendan persisted after adjusting for all baseline variables. A longer time to reach the endpoint was also associated with being a Cavalier King Charles Spaniel, requiring a lower furosemide dose, and having a higher creatinine concentration. Increases in several indicators of cardiac enlargement (left atrial to aortic root ratio, vertebral heart scale, and percentage increase in left ventricular internal diameter in systole) were associated with a shorter time to endpoint, as was a worse tolerance for exercise. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan plus conventional therapy prolongs time to sudden death, euthanasia for cardiac reasons, or treatment failure in dogs with CHF caused by MMVD compared with benazepril plus conventional therapy.

Assessing aortic stenosis using sample entropy of the phonocardiographic signal in dogs.

In aortic valve stenosis (AS), heart murmurs arise as an effect of turbulent blood flow distal to the obstructed valves. With increasing AS severity, the flow becomes more unstable, and the ensuing murmur becomes more complex. We hypothesize that these hemodynamic flow changes can be quantified based on the complexity of the phonocardiographic (PCG) signal. In this study, sample entropy (SampEn) was investigated as a measure of complexity using a dog model. Twenty-seven boxer dogs with various degrees of AS were examined with Doppler echocardiography, and the peak aortic flow velocity ( V(max)) was used as a reference of AS severity. SampEn correlated to V(max) with R = 0.70 using logarithmic regression. In a separate analysis, significant differences were found between physiologic murmurs and murmurs caused by AS ( p << 0.05), and the area under a receiver operating characteristic curve was calculated to 0.96. Comparison with previously presented PCG measures for AS assessment showed improved performance when using SampEn, especially for differentiation between physiological murmurs and murmurs caused by mild AS. Studies in patients will be needed to properly assess the technique in humans.

Low intensity heart murmurs in boxer dogs: inter-observer variation and effects of stress testing.

Inter-observer variation in the detection and grading of low intensity heart murmurs in boxer dogs was investigated. Six veterinarians with different levels of experience examined 27 boxers by cardiac auscultation. The dogs were auscultated before and after exercise, and the results were compared with phonocardiographic and echocardiographic examinations performed at rest and during two different stress tests. A subvalvular aortic ridge was identified in six dogs on two-dimensional echocardiography. Using dogs with low intensity murmurs or dogs free of heart murmurs, inter-observer agreement was positively correlated to the level of experience at rest (weighted kappa [kappa] 0.14 to 0.75), while the agreement was poor after exercise (weighted kappa 0.01 to 0.36). The presence of a subvalvular aortic ridge was associated with higher aortic flow velocities (P<0.002) and higher auscultatory murmur grading (P<0.001). There was an increase in murmur duration during one kind of stress test (P<0.001) and in aortic flow velocity during the other (P=0.001).

Prevalence of murmurs consistent with aortic stenosis among boxer dogs in Norway and Sweden.

The prevalence and severity of cardiac murmurs consistent with subclinical or clinically detectable aortic stenosis among purebred boxer dogs in Norway and Sweden were evaluated. Two hundred and thirty-one boxers, randomly selected or investigated at dog shows, were examined by phonocardiography by two veterinarians and classified on the basis of the characteristics of their murmurs into categories 0 to 4. No murmur was detected in 23 per cent of the dogs, murmurs classified as category 1 were diagnosed in 25 per cent of the dogs, as category 2 in 46 per cent, as category 3 in 7 per cent cent, and two dogs had category 4 murmurs. In 55 per cent of the dogs, primarily those with very soft murmurs, there was some variation in the intensity of the murmur from beat to beat. The prevalence of cardiac murmurs among Norwegian and Swedish boxers was high and similar to the prevalence reported in Great Britain.

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.

Analysis of murmur intensity, duration and frequency components in dogs with aortic stenosis.

A study was undertaken to investigate the relationship between murmur intensity, murmur duration, duration to peak intensity and frequency components with degree of aortic stenosis in boxers. Measurements were made from phonocardiograms obtained from 35 boxers with ejection-type murmurs, and values were compared with those obtained for aortic flow velocity measured by Doppler echocardiography. Murmur intensity graded by auscultation was significantly correlated with aortic flow velocity (P < 0.001), and murmur duration, expressed as a percentage of systole was significantly correlated with aortic flow velocity (P < 0.001), independent of heart rate. Dogs with early systolic murmurs not exceeding 50 per cent of systole had aortic flow velocities of less than 1.5 m/second and no echocardiographic abnormalities, in contrast with dogs with murmurs of longer duration. Dogs with only high frequency components had lower aortic velocities than those that also had components in the medium frequency range (P < 0.01).

Effects of naturally acquired decompensated mitral valve regurgitation on the renin-angiotensin-aldosterone system and atrial natriuretic peptide concentration in dogs.

OBJECTIVE: To investigate activity of the renin-angiotensin-aldosterone system and N-terminal pro-atrial natriuretic peptide (NT-proANP) during development of clinical signs of decompensated mitral valve regurgitation (MR). ANIMALS: 11 Cavalier King Charles Spaniels with advanced MR attributable to chronic valvular disease. PROCEDURE: Dogs were subjected to repeated examinations at 6-month intervals until signs of decompensation had developed (end point). Data acquired at end point were compared with data obtained from examinations 1 year and 1 to 6 months before decompensation. Each examination included physical examination, collection of venous blood, thoracic radiography, and echocardiography. RESULTS: Echocardiographic measurements of left atrial-to-aortic root ratio and left ventricular end diastolic diameter increased considerably during the study, whereas left ventricular end systolic diameter remained unchanged. The increase in cardiac size was associated with increased plasma concentration of NT-proANP. In contrast, plasma concentrations of aldosterone and angiotensin II were reduced at decompensation (aldosterone compared with the 2 earlier examinations and angiotensin II compared with values obtained 1 to 6 months before), despite decreased plasma protein concentration and hematocrit, suggesting fluid retention. The urine-to-plasma creatinine ratio was reduced at end point. CONCLUSION AND CLINICAL IMPLICATIONS: Early decompensated MR in dogs was not associated with increased circulating renin-angiotensin-aldosterone system activity, which may be caused by increased activity of ANP, and may be important for future therapeutic strategies of MR.

Effects of long-term treatment with enalapril or hydralazine on the renin-angiotensin-aldosterone system and fluid balance in dogs with naturally acquired mitral valve regurgitation.

OBJECTIVE: To study long-term effects of enalapril, an angiotensin-converting enzyme inhibitor, and hydralazine, an arteriodilator, on renin-angiotensin-aldosterone system and fluid balance before and after administration of furosemide. ANIMALS: 22 dogs with clinical signs of congestive heart failure (CHF) attributable to mitral regurgitation. PROCEDURE: After initial examination, 12 dogs received enalapril and 10 received hydralazine. Dogs were re-examined 3 weeks and 6 months after initial examination. Furosemide was added after the 3-week examination, and at 6 months, dogs had received furosemide for at least 4 months. RESULTS: Angiotensin II and aldosterone plasma concentrations were low before treatment, and only aldosterone became significantly decreased after enalapril monotherapy. Concentrations of both hormones and heart rate increased in dogs receiving hydralazine monotherapy, and fluid retention was evident. After long-term treatment with either of the 2 drugs together with furosemide, angiotensin II and aldosterone values increased in both groups. Natriuresis and kaliuresis developed in all dogs, with greatest effect in those receiving enalapril and furosemide. These dogs had decreased plasma sodium concentration, whereas potassium concentration was equally decreased in both groups. After 6 months, the enalapril group, but not the hydralazine group, had increased cardiac size. All dogs had moderate reduction of weight and were azotemic, although changes were more pronounced in those of the hydralazine group. CONCLUSION: The 2 drugs have different effects on the renin-angiotensin-aldosterone system and fluid balance in dogs with CHF.

Relationship between parental cardiac status in Cavalier King Charles spaniels and prevalence and severity of chronic valvular disease in offspring.

OBJECTIVE: To study the relationship between parental cardiac status in Cavalier King Charles Spaniels and development of chronic valvular disease (CVD) in offspring. DESIGN: Historical cohort. ANIMALS: 54 female and 53 male Cavalier King Charles Spaniel offspring. PROCEDURE: 7 sires, selected on the basis of their liability to develop CVD, were screened for clinical signs of CVD and assigned to 1 of 3 groups (late, intermediate, and early onset of CVD). The mates of these sires (30 dams) were selected and classified likewise, and 107 offspring produced in 1988 from matings between these parents were screened for clinical signs of CVD at a mean age of 5.3 +/- 0.3 years. RESULTS: 55% of the offspring were free from clinical signs of CVD, whereas 45% had cardiac murmurs of low or moderate intensity. The proportion of offspring with heart murmurs and the intensity of murmurs were significantly greater with increased parental classification. More males than females had developed murmurs, and murmurs of moderate intensity also were more prevalent in males. Results of multiple-regression analysis indicated that mean parental classification and sex had significant effects on proportion of offspring with murmurs and their intensity. Additionally, age affected disease prevalence and severity, despite the narrow range in age of offspring examined. CLINICAL IMPLICATIONS: Parental CVD status is an important factor influencing the probability of heart murmurs and their intensity in offspring. The results of this study indicate that CVD development is a polygenic threshold trait and that sex of the offspring influences threshold levels.

Heart rate variability in relation to severity of mitral regurgitation in Cavalier King Charles spaniels.

Heart rate variability was measured in 81 Cavalier King Charles spaniels to investigate if it could be used to evaluate the severity of mitral regurgitation and to predict decompensation. Heart rate variability was assessed by the natural logarithm of the variance of the R-R intervals for 20 consecutive beats obtained from electrocardiographic recordings. Twenty-two of the dogs were clinically normal and 59 had mitral regurgitation caused by chronic valvular disease. The severity of mitral regurgitation was evaluated by echocardiography and thoracic radiography. Heart rate variability was found to be reduced (P < 0.001) among dogs with severe left atrial and ventricular dilatation and clinical signs of congestion. No significant differences in heart rate variability were found among normal dogs, dogs with only cardiac murmur, and dogs with echoradiographic evidence of slight to moderate left atrial and ventricular dilatation. Overall, an association was found between heart rate variability and left atrial to aortic root ration and left ventricular end diastolic diameters (r = 0.72 and 0.64, respectively, P < 0.001), as well as heart and respiratory rate (r = 0.80 and 0.69, respectively, P < 0.001). Multiregression analysis showed that, in order of importance, heart rate, left atrial diameter and respiratory rate had significant effects on heart rate variability. Among these parameters, heart rate variability and left atrial diameter were found to be most efficient in separating decompensated dogs from compensated. It is concluded that heart rate variability may provide the clinician with valuable information when assessing the severity of mitral regurgitation caused by chronic valvular disease.