The predictive value of clinical, radiographic, echocardiographic variables and cardiac biomarkers for assessing risk of the onset of heart failure or cardiac death in dogs with preclinical myxomatous mitral valve disease enrolled in the DELAY study.

OBJECTIVES: To identify the predictive value on time to onset of heart failure (HF) or cardiac death of clinical, radiographic, and echocardiographic variables, as well as cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I in dogs with preclinical myxomatous mitral valve disease (MMVD). ANIMALS: One hundred sixty-eight dogs with preclinical MMVD and left atrium to aortic root ratio ≥1.6 (LA:Ao) and normalized left ventricular end-diastolic diameter ≥1.7 were included. METHODS: Prospective, randomized, multicenter, single-blinded, placebo-controlled study. Clinical, radiographic, echocardiographic variables and plasma cardiac biomarkers concentrations were compared at different time points. Using receiving operating curves analysis, best cutoff for selected variables was identified and the risk to develop the study endpoint at six-month intervals was calculated. RESULTS: Left atrial to aortic root ratio >2.1 (hazard ratio [HR] 3.2, 95% confidence interval [95% CI] 1.9-5.6), normalized left ventricular end-diastolic diameter > 1.9 (HR: 6.3; 95% CI: 3.3-11.8), early transmitral peak velocity (E peak) > 1 m/sec (HR: 3.9; 95% CI: 2.3-6.7), and NT-proBNP > 1500 ρmol/L (HR: 5.7; 95% CI: 3.3-9.5) were associated with increased risk of HF or cardiac death. The best fit model to predict the risk to reach the endpoint was represented by the plasma NT-proBNP concentrations adjusted for LA:Ao and E peak. CONCLUSIONS: Logistic and survival models including echocardiographic variables and NT-proBNP can be used to identify dogs with preclinical MMVD at higher risk to develop HF or cardiac death.

DELay of Appearance of sYmptoms of Canine Degenerative Mitral Valve Disease Treated with Spironolactone and Benazepril: the DELAY Study.

INTRODUCTION: Efficacy of renin-angiotensin-aldosterone system (RAAS) blockade using angiotensin-converting enzyme inhibitors (ACEi) in dogs with preclinical myxomatous mitral valve disease (MMVD) is controversial. HYPOTHESIS: Administration of spironolactone (2-4 mg q 24 h) and benazepril (0.25-0.5 mg q 24 h) in dogs with preclinical MMVD, not receiving any other cardiac medications, delays the onset of heart failure (HF) and cardiac-related death. Moreover, it reduces the progression of the disease as indicated by echocardiographic parameters and level of cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI). ANIMALS: 184 dogs with pre-clinical MMVD and left atrium-to-aortic root ratio (LA:Ao) ≥1.6 and normalized left ventricular end-diastolic diameter (LVEDDn) ≥1.7. METHODS: This is a prospective, randomized, multicenter, single-blinded, placebo-controlled study. Primary outcome variable was time-to-onset of first occurrence of HF or cardiac death. Secondary end points included effect of treatment on progression of the disease based on echocardiographic and radiographic parameters, as well as variations of NT-proBNP and cTnI concentrations. RESULTS: The median time to primary end point was 902 days (95% confidence interval (CI) 682-not available) for the treatment group and 1139 days (95% CI 732-NA) for the control group (p = 0.45). Vertebral heart score (p = 0.05), LA:Ao (p < 0.001), LVEDDn (p < 0.001), trans-mitral E peak velocity (p = 0.011), and NT-proBNP (p = 0.037) were lower at the end of study in the treatment group. CONCLUSIONS: This study failed in demonstrating that combined administration of spironolactone and benazepril delays onset of HF in dogs with preclinical MMVD. However, such treatment induces beneficial effects on cardiac remodeling and these results could be of clinical relevance.

Longitudinal Analysis of Quality of Life, Clinical, Radiographic, Echocardiographic, and Laboratory Variables in Dogs with Preclinical Myxomatous Mitral Valve Disease Receiving Pimobendan or Placebo: The EPIC Study.

BACKGROUND: Changes in clinical variables associated with the administration of pimobendan to dogs with preclinical myxomatous mitral valve disease (MMVD) and cardiomegaly have not been described. OBJECTIVES: To investigate the effect of pimobendan on clinical variables and the relationship between a change in heart size and the time to congestive heart failure (CHF) or cardiac-related death (CRD) in dogs with MMVD and cardiomegaly. To determine whether pimobendan-treated dogs differ from dogs receiving placebo at onset of CHF. ANIMALS: Three hundred and fifty-four dogs with MMVD and cardiomegaly. MATERIALS AND METHODS: Prospective, blinded study with dogs randomized (ratio 1:1) to pimobendan (0.4-0.6 mg/kg/d) or placebo. Clinical, laboratory, and heart-size variables in both groups were measured and compared at different time points (day 35 and onset of CHF) and over the study duration. Relationships between short-term changes in echocardiographic variables and time to CHF or CRD were explored. RESULTS: At day 35, heart size had reduced in the pimobendan group: median change in (Δ) LVIDDN -0.06 (IQR: -0.15 to +0.02), P < 0.0001, and LA:Ao -0.08 (IQR: -0.23 to +0.03), P < 0.0001. Reduction in heart size was associated with increased time to CHF or CRD. Hazard ratio for a 0.1 increase in ΔLVIDDN was 1.26, P = 0.0003. Hazard ratio for a 0.1 increase in ΔLA:Ao was 1.14, P = 0.0002. At onset of CHF, groups were similar. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan treatment reduces heart size. Reduced heart size is associated with improved outcome. At the onset of CHF, dogs treated with pimobendan were indistinguishable from those receiving placebo.

Heart rate turbulence after ventricular premature beats in healthy Doberman pinschers and those with dilated cardiomyopathy.

OBJECTIVES: To describe the measurement of heart rate turbulence (HRT) after ventricular premature beats and compare HRT in healthy Doberman pinschers and those with dilated cardiomyopathy (DCM), with and without congestive heart failure (CHF). ANIMALS: Sixty-five client-owned Dobermans: 20 healthy (NORMAL), 31 with preclinical DCM and 14 with DCM and CHF (DCM + CHF). METHODS: A retrospective study of data retrieved from clinical records and ambulatory ECG (Holter) archives, including data collected previously for a large-scale prospective study of Dobermans with preclinical DCM. Holter data were reanalysed quantitatively, including conventional time-domain heart rate variability and the HRT parameters turbulence onset and turbulence slope. RESULTS: Heart rate turbulence could be measured in 58/65 dogs. Six Holter recordings had inadequate ventricular premature contractions (VPCs) and one exhibited VPCs too similar to sinus morphology. Heart rate turbulence parameter, turbulence onset, was significantly reduced in DCM dogs, whereas conventional heart rate variability measures were not. Heart rate variability and HRT markers were reduced in DCM + CHF dogs as expected. CONCLUSIONS: Heart rate turbulence can be measured from the majority of good quality standard canine 24-hour Holter recordings with >5 VPCs. Turbulence onset is significantly reduced in Dobermans with preclinical DCM which indicates vagal withdrawal early in the course of disease. Heart rate turbulence is a powerful prognostic indicator in human cardiac disease which can be measured from standard 24-hour ambulatory ECG (Holter) recordings using appropriate computer software. Further studies are warranted to assess whether HRT may be of prognostic value in dogs with preclinical DCM and in other canine cardiac disease.

Echocardiographic assessments of longitudinal left ventricular function in healthy English Springer spaniels.

OBJECTIVES: To establish reference intervals for echocardiographic measures of longitudinal left ventricular function in adult English Springer spaniel (ESS) dogs. ANIMALS: This study involved 42 healthy adult ESS. METHODS: Animals were prospectively recruited from a general practice population in the United Kingdom. Dogs were examined twice, at least 12 months apart, to exclude dogs with progressive cardiac disease. Mitral annular plane systolic excursion, tissue Doppler imaging mitral annular velocities and two-dimensional speckle-tracking echocardiographic left ventricular longitudinal strain and strain rate were measured. Intraoperator and intraobserver variability were examined and reference intervals were calculated. The potential effects of body weight, age and heart rate on these variables were examined. RESULTS: Intraoperator and intraobserver variability was <10% for all parameters except tissue Doppler imaging E' (the peak velocity of early diastolic mitral annular motion as determined by pulsed wave Doppler) and two-dimensional speckle-tracking echocardiographic variables, which were all <20%. Thirty-nine dogs were used to create reference intervals. Significant (but mostly weak) effects of age, heart rate and body weight on were detected. Reference intervals were similar to previously published values in different breeds. CLINICAL SIGNIFICANCE: Breed specific reference intervals for measures of longitudinal left ventricular function in the ESS are presented.

Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study-A Randomized Clinical Trial.

BACKGROUND: Pimobendan is effective in treatment of dogs with congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD). Its effect on dogs before the onset of CHF is unknown. HYPOTHESIS/OBJECTIVES: Administration of pimobendan (0.4-0.6 mg/kg/d in divided doses) to dogs with increased heart size secondary to preclinical MMVD, not receiving other cardiovascular medications, will delay the onset of signs of CHF, cardiac-related death, or euthanasia. ANIMALS: 360 client-owned dogs with MMVD with left atrial-to-aortic ratio ≥1.6, normalized left ventricular internal diameter in diastole ≥1.7, and vertebral heart sum >10.5. METHODS: Prospective, randomized, placebo-controlled, blinded, multicenter clinical trial. Primary outcome variable was time to a composite of the onset of CHF, cardiac-related death, or euthanasia. RESULTS: Median time to primary endpoint was 1228 days (95% CI: 856-NA) in the pimobendan group and 766 days (95% CI: 667-875) in the placebo group (P = .0038). Hazard ratio for the pimobendan group was 0.64 (95% CI: 0.47-0.87) compared with the placebo group. The benefit persisted after adjustment for other variables. Adverse events were not different between treatment groups. Dogs in the pimobendan group lived longer (median survival time was 1059 days (95% CI: 952-NA) in the pimobendan group and 902 days (95% CI: 747-1061) in the placebo group) (P = .012). CONCLUSIONS AND CLINICAL IMPORTANCE: Administration of pimobendan to dogs with MMVD and echocardiographic and radiographic evidence of cardiomegaly results in prolongation of preclinical period and is safe and well tolerated. Prolongation of preclinical period by approximately 15 months represents substantial clinical benefit.

Reference intervals for transthoracic echocardiography in the English springer spaniel: a prospective, longitudinal study.

OBJECTIVES: To establish transthoracic echocardiographic reference intervals in adult English springer spaniel dogs. METHODS: Forty-two healthy adult English springer spaniels were prospectively recruited from a general practice population in the UK. Animals were examined twice, at least 12 months apart, to exclude dogs with progressive cardiac disease. Reference intervals were calculated using Box-Cox transformations and specific variables were depicted within an expert consensus range. Relationships of body mass, age and heart rate with cardiac structure and function were examined and functional assessments were compared with previous reports. Reference intervals were compared against published ratiometric indices and allometric scaling models. RESULTS: Thirty-nine dogs contributed to create the reference intervals. Significant relationships with bodyweight, age and heart rate were detected, although low coefficients of determination were found. Fractional shortening values were lower than has been reported in many breeds but Simpson-derived ejection fractions were similar to previously published breed-specific values. CLINICAL SIGNIFICANCE: Breed-specific reference intervals are reported allowing for more appropriate interpretation of echocardiographic assessments in the English springer spaniel.

The times they are a-changin': Two-dimensional aortic valve measurements differ throughout diastole.

INTRODUCTION: Diastolic aortic valve measurements are used to obtain weight-independent cardiac ratiometric indices. However, whether clinically important variations in valve measurements occur during diastole remains undetermined. ANIMALS: One hundred sixty-three dogs and 40 cats; a mixture of healthy animals and patients with heart disease. MATERIALS AND METHODS: Aortic valve diameter and area were measured at three time-points: early diastole {AoMAX}, during the P-wave {AoP} and at end-diastole {AoMIN}. Measurement beat-to-beat variability was determined. Difference plots were generated for each measurement pair. Aortic measurements were compared by repeated measures analysis of variance. RESULTS: In dogs, normalised aortic diameters showed a fixed bias of approximately 14% for AoMAX-AoMIN, 6% for AoMAX-AoP and 8% for AoP-AoMIN. In cats, the aortic diameter and area biases were all less than 2.5% and less than 7% respectively. AoMAX was the largest measurement in 78% patients and AoMIN was the smallest measurement in 73% patients. In dogs, AoMAX > AoP > AoMIN (p < 0.0001). Median within-patient measurement variability was 5% for linear dimensions and 8% for area measurements in dogs and 4.5% for linear and 10.4% for area in cats. DISCUSSION: Aortic measurements in dogs differ significantly throughout diastole, with Ao(A)MAX > Ao(A)P > Ao(A)MIN. These differences could clinically impact cardiac ratiometric indices. The difference in cats is less than the within-patient measurement variability and unlikely to be of clinical significance. CONCLUSIONS: Operators should adopt a single diastolic time-point for measurement of the aorta to ensure consistency in measuring and reporting in echocardiography.

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.

Efficacy of pimobendan in the prevention of congestive heart failure or sudden death in Doberman Pinschers with preclinical dilated cardiomyopathy (the PROTECT Study).

BACKGROUND: The benefit of pimobendan in delaying the progression of preclinical dilated cardiomyopathy (DCM) in Dobermans is not reported. HYPOTHESIS: That chronic oral administration of pimobendan to Dobermans with preclinical DCM will delay the onset of CHF or sudden death and improve survival. ANIMALS: Seventy-six client-owned Dobermans recruited at 10 centers in the UK and North America. METHODS: The trial was a randomized, blinded, placebo-controlled, parallel group multicenter study. Dogs were allocated in a 1:1 ratio to receive pimobendan (Vetmedin capsules) or visually identical placebo. The composite primary endpoint was prospectively defined as either onset of CHF or sudden death. Time to death from all causes was a secondary endpoint. RESULTS: The proportion of dogs reaching the primary endpoint was not significantly different between groups (P = .1). The median time to the primary endpoint (onset of CHF or sudden death) was significantly longer in the pimobendan (718 days, IQR 441-1152 days) versus the placebo group (441 days, IQR 151-641 days) (log-rank P = 0.0088). The median survival time was significantly longer in the pimobendan (623 days, IQR 491-1531 days) versus the placebo group (466 days, IQR 236-710 days) (log-rank P = .034). CONCLUSION AND CLINICAL IMPORTANCE: The administration of pimobendan to Dobermans with preclinical DCM prolongs the time to the onset of clinical signs and extends survival. Treatment of dogs in the preclinical phase of this common cardiovascular disorder with pimobendan can lead to improved outcome.

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.

Discospondylitis in an adult horse.

Discospondylitis, of presumed bacterial origin, was diagnosed in an adult thoroughbred racehorse. The clinical signs were vague and associated with abnormal mobility of the neck and forelimbs. Clinical pathology showed only a non-specific inflammatory response. A scintigraphic examination revealed the site of the lesion and the diagnosis was confirmed by the identification of radiographic changes affecting two thoracic vertebrae. A prolonged course of antimicrobial agents produced a complete recovery and the horse returned to full athletic use.

Echocardiographic measurements of cardiac dimensions and indices of cardiac function in normal adult thoroughbred horses.

Cardiac dimensions and indices of cardiac function were measured in 29 clinically normal adult Thoroughbreds (TB) which performed minimal exercise using guided M-mode and two-dimensional (2-D) echocardiography, from a variety of image planes and measurement methods, and standardised imaging planes based on intracardiac anatomical landmarks. The different methods of measuring these variables were compared. The variables which were considered to be most valuable for quantitative echocardiography were measured in a further 9 horses. Comparable measurements of cardiac dimensions can be obtained from a variety of different imaging planes, using either 2-D or guided M-mode echocardiography from the left or right side of the chest, although differences in measurement methods must be taken into account. The results of this study give a useful range of dimensions and indices of cardiac function in normal adult TBs for comparison with those recorded from horses with suspected cardiac disease. Comparisons are only valid if there is meticulous attention to correct orientation of imaging planes with regard to internal landmarks and that comparable measurement locations and timing are used.

Effects of sedation with detomidine hydrochloride on echocardiographic measurements of cardiac dimensions and indices of cardiac function in horses.

Twenty-six horses were sedated with detomidine hydrochloride (Domosedan, SmithKline Beecham Animal Health, Tadworth, Surrey, UK) at a dose of 10 micrograms/kg bwt, administered i.v. Echocardiograms were recorded before and after sedation, measurements of cardiac dimensions were made and functional indices were calculated. The pre- and post sedation values were compared. No significant change was detected following sedation in the ejection time (ET), left ventricular dimension, left atrial diameter at the sinotubular junction at end-systole or end-diastole or at the sinus of Valsalva at end-diastole. Sedation was found to result in a statistically significant increase in end-systolic left ventricular diameter and internal area and aortic diameter measured at the sinus of Valsalva. Left ventricular free-wall thickness and interventricular septal thickness at end-systole, fractional shortening, fractional area change and heart rate were significantly reduced following sedation. A significant increase in pre-ejection period (PEP), duration of electromechanical systole (EMS) and PEP/ET (ejection time) was detected.

Angiostrongylus vasorum infection in seven dogs.

Angiostrongylus vasorum infection was diagnosed in six dogs by the identification of larvae in sputum or faeces, or by the identification of adult worms post mortem. In another dog strong evidence of the condition was obtained but no parasites were identified. In four cases the main clinical signs were coughing and dyspnoea, but one dog had exercise intolerance and no history of coughing. One dog in which larvae were found in the faeces had no clinical signs that were related to the infection. Another dog had flaccid hindlimb paralysis and forelimb hypermetria-clinical signs of the disease which have not been reported previously. Four of the cases came from south Wales, one of them being the first case of the infection to be reported from this area.

A survey of cardiac auscultatory findings in horses.

Auscultation was used to examine 545 horses for cardiac murmurs and some arrhythmias. The most significant finding was the high prevalence of right-sided holosystolic or pansystolic plateau-type murmurs compatible with a diagnosis of tricuspid regurgitation in National Hunt racing Thoroughbreds of all ages (16.4%). This condition was found in 4.7% of flat-racing Thoroughbreds, 3.7% of non-racing Thoroughbreds and Thoroughbred crosses, and in none of the ponies examined. High prevalences of left-sided early systolic murmurs (53%), left-sided early diastolic murmurs (23%), right-sided early diastolic murmurs (22%) and second degree atrioventricular block (23%) were found in racehorses of both types.

Effects of Stabilizing the Nontested Lower Extremity during lsokinetic Evaluation of the Quadriceps and Hamstrings*.

The purpose of this investigation was to determine if stabilization of the nontested lower extremity influences the peak torque generated by the knee musculature of the opposite extremity during isokinetic testing. The subjects included 15 males and 15 females, between 18 to 30 years of age, who had no history of right knee pain or pathology. A Cybex I isokinetic dynamometer was used to measure the torques generated by the quadriceps and hamstring muscles of the right lower extremity during flexion and extension. Each subject performed two trials of extension and flexion of the right knee; each trial consisted of one set of three contractions at 60 degrees /sec and one set at 180 degrees /sec. One trial was performed with the left lower extremity stabilized and the second trial was performed without stabilization. The results demonstrate that the peak torques generated by the quadriceps and hamstrings of the tested extremity are not significantly influenced by stabilization of the opposite lower extremity at the speeds tested.J Orthop Sports Phys Ther 1984;6(1):18-20.