Association between atrial fibrillation and right-sided manifestations of congestive heart failure in dogs with degenerative mitral valve disease or dilated cardiomyopathy

IntroductionTo determine whether dogs with atrial fibrillation (AF) are more likely to develop right-sided manifestations of congestive heart failure (R-CHF) than dogs without AF.AnimalsTwo hundred twenty dogs diagnosed with congestive heart failure (CHF) secondary to degenerative mitral valve disease (DMVD, n = 155) or dilated cardiomyopathy (DCM, n = 65) at a referral institution.MethodsMedical records were reviewed to extract relevant clinical and echocardiographic data.ResultsFifty dogs had AF at the time of CHF diagnosis, including 17/155 (11.0%) dogs with DMVD and 33/65 (50.8%) dogs with DCM. Sixty dogs had R-CHF evidenced by cavitary effusions. Among DMVD dogs, R-CHF occurred in 13/17 (76.5%) dogs with AF compared with 10/138 (7.2%) dogs without AF; among DCM dogs, R-CHF occurred in 24/33 (72.7%) dogs with AF compared with 13/32 (40.6%) dogs without AF. Dogs with AF were more likely to manifest R-CHF signs than dogs without AF (p < 0.0001 for DMVD; p = 0.0125 for DCM). The presence of AF, diagnosis of DCM, and moderate to severe tricuspid regurgitation were associated with R-CHF in multivariate analysis. AF was the strongest predictor of R-CHF (odds ratio, 14.44; 95% confidence interval, 5.75–36.26).ConclusionsDogs with AF are more likely to manifest R-CHF than dogs without AF. Cavitary effusions are an expected finding in approximately three-quarters of dogs with AF and CHF secondary to either DCM or DMVD.     

Effect of cilobradine in cats with a first episode of congestive heart failure due to primary cardiomyopathy

IntroductionHeart rate (HR) is often elevated in cats with cardiomyopathies (CMPs). Pharmacologic modulation of HR may reduce cardiac morbidity and mortality.ObjectivesTo investigate the effects of cilobradine vs. placebo, regarding time to cardiac mortality or morbidity in cats with first episode of congestive heart failure (CHF) due to primary CMP.AnimalsThree hundred and sixty-seven client-owned cats with primary CMP that had presented with a first episode of CHF at 50 centers in Europe. Per-protocol population comprised 193 cats (n = 89 cilobradine, n = 104 placebo). An interim analysis for futility was planned.MethodsProspective, randomized, placebo-controlled, double-blinded, multicenter clinical trial. Primary outcome variable was the time to a composite of cardiac mortality or cardiac morbidity.ResultsMedian time to primary outcome was 84 days (95% confidence interval [CI]: 63–219 days) in the cilobradine group (CG) and 203 days in the placebo group (95% CI: 145–377 days) with observed hazard ratio of 1.44, indicating a higher hazard for the CG (P = 0.057). Mean HR was 28 beats per minute (bpm) lower at Day 7 (P < 0.0001) and remained 29 bpm lower at Day 360 (P = 0.026) in the CG than that in the placebo group. Although the number of adverse events did not differ, there were more serious adverse events in the CG.ConclusionsHeart rate reduction by cilobradine in cats with a first episode of CHF due to primary CMP did not reduce cardiac mortality and morbidity.     

Association of diet with clinical outcomes in dogs with dilated cardiomyopathy and congestive heart failure

IntroductionDilated cardiomyopathy (DCM) in dogs has been associated with feeding of grain-free (GF), legume-rich diets. Some dogs with presumed diet-associated DCM have shown improved myocardial function and clinical outcomes following a change in diet and standard medical therapy.HypothesisPrior GF (pGF) diet influences reverse cardiac remodeling and clinical outcomes in dogs with DCM and congestive heart failure (CHF).Animals and methodsA retrospective study was performed with 67 dogs with DCM and CHF for which diet history was known. Dogs were grouped by diet into pGF and grain-inclusive (GI) groups. Dogs in the pGF group were included if diet change was a component of therapy. Survival was analyzed using Kaplan–Meier curves and the Cox proportional-hazards model.ResultsThe median survival time was 344 days for pGF dogs vs. 253 days for GI dogs (P = 0.074). Statistically significant differences in median survival were identified when the analysis was limited to dogs surviving longer than one week (P = 0.033). Prior GF dogs had a significantly worse outcome the longer a GF diet was fed prior to diagnosis (P = 0.004) or if they were diagnosed at a younger age (P = 0.017). Prior GF dogs showed significantly greater improvement in normalized left ventricular internal diastolic diameter (P = 0.038) and E-point septal separation (P = 0.031) measurements and significant decreases in their furosemide (P = 0.009) and pimobendan (P < 0.005) dosages over time compared to GI dogs.ConclusionsPrior GF dogs that survived at least one week after diagnosis of DCM, treatment of CHF, and diet change had better clinical outcomes and showed reverse ventricular remodeling compared to GI dogs.     

Canine idiopathic dilated cardiomyopathy. Part I: Aetiology, clinical characteristics, epidemiology and pathology

Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The aetiology of the myocardial hypokineis is seldom known in the individual case of DCM, although several theories concerning genetic, nutritional, metabolic, inflammatory, infectious, or drug- or toxin-induced myocardial disease have been discussed. DCM is often referred to as being breed-specific for Boxers, Doberman Pinschers, English Cocker Spaniels and other breeds. Review of reports on histopathologic findings in canine DCM reveals two histologically distinct forms of DCM; (1) cardiomyopathy of boxers and of Doberman pinschers, corresponding to the "fatty infiltration-degenerative" type, and (2) the form seen in many giant, large- and medium-sized breeds, including some boxers and Doberman pinschers, which can be classified as the "attenuated wavy fiber" type of DCM. The classification of canine idiopathic DCM according to histologic findigns seems superior to classification suggesting breed-specific syndromes, as some breeds (i.e. boxers and Doberman pinschers) may be affected by both diseases. However, ante mortem aetiological diagnosis of DCM is difficult. DCM carries a poor prognosis in dogs, and few prognostic indicators have been identified.     

Assessment of diastolic function by Doppler echocardiography in normal Doberman Pinschers and Doberman Pinschers with dilated cardiomyopathy

BACKGROUND: Assessment of diastolic function in patients with dilated cardiomyopathy (DCM) has the potential to add valuable information regarding hemodynamics, disease severity, and prognosis. The purpose of this study was to determine transmitral flow (TMF), isovolumic relaxation time (IVRT), pulmonary venous flow (PVF), flow propagation velocity (Vp), and mitral annular velocities by tissue Doppler in Doberman Pinschers with and without DCM. HYPOTHESIS: It was anticipated that normal and DCM Dobermans would differ with respect to these parameters, and that associations with time to congestive heart failure (CHF) or death would be found. ANIMALS: Thirty client-owned Doberman Pinschers (10 each of normal, occult DCM, and overt DCM) were studied. METHODS: Each dog underwent echocardiography with or without thoracic radiography (to confirm CHF) for classification as normal or DCM-affected, followed by collection of echocardiographic diastolic parameters. RESULTS: The group with occult DCM exhibited features of pseudonormal TMF, reduced systolic to diastolic PVF ratio, and reduced Vp. Shorter early TMF deceleration time (DTE) was associated with shorter time to CHF or sudden death. The group with overt DCM exhibited restrictive TMF, blunted systolic PVF, and reduced early and late diastolic mitral annular velocities. CONCLUSIONS AND CLINICAL IMPORTANCE: Doberman Pinschers showed evidence of moderate and severe diastolic dysfunction in occult and overt DCM, respectively. Short DTE may be a useful predictor of onset of CHF or sudden death.     

Effect of pimobendan on case fatality rate in Doberman Pinschers with congestive heart failure caused by dilated cardiomyopathy

BACKGROUND: Despite traditional therapy of a diuretic, angiotensin converting enzyme inhibitor, digoxin, or a combination of these drugs, survival of dogs with dilated cardiomyopathy (DCM) is low. Pimobendan, an inodilator, has both inotropic and balanced peripheral vasodilatory properties. HYPOTHESIS: Pimobendan when added to conventional therapy will improve morbidity and reduce case fatality rate in Doberman Pinschers with congestive heart failure (CHF) caused by DCM. ANIMALS: Sixteen Doberman Pinschers in CHF caused by DCM. METHODS: A prospective randomized, double-blind, placebo-controlled study with treatment failure as the primary and quality of life (QoL) indices as secondary outcome variables. Therapy consisted of furosemide (per os [PO] as required) and benazepril hydrochloride (0.5 mg/kg PO q12h) and dogs were randomized in pairs and by sex to receive pimobendan (0.25 mg/kg PO q12h) or placebo (1 tablet PO q12h). RESULTS: Pimobendan-treated dogs had a significant improvement in time to treatment failure (pimobendan median, 130.5 days; placebo median, 14 days; P= .002; risk ratio = 0.35, P= .003, lower 5% confidence limit = 0.13, upper 95% confidence limit = 0.71). Number and rate of dogs reaching treatment failure in the placebo group precluded the analysis of QoL. CONCLUSIONS AND CLINICAL IMPORTANCE: Pimobendan should be used as a first-line therapeutic in Doberman Pinschers for the treatment of CHF caused by DCM.     

Change of Vertebral Left Atrial Size in Dogs With Preclinical Myxomatous Mitral Valve Disease Prior to the Onset of Congestive Heart Failure

Introduction/objectivesIt has been proposed that vertebral left atrial size (VLAS) on thoracic radiographs can be used to assess the left atrial enlargement in dogs with myxomatous mitral valve disease (MMVD). However, it remains unclear whether VLAS can be used to distinguish dogs between pre-clinical MMVD that are at a greater risk of developing congestive heart failure (CHF) from those at a lower risk. We investigated this possibility.Animals, materials and methodsForty-one dogs with MMVD were retrospectively classified into one of two groups, a group that developed CHF (group CHF, n = 17) or remained CHF-free (group no-CHF, n = 24). The value of vertebral heart scale (VHS) and VLAS at three time-points, change in VHS and VLAS at a specific time interval (ΔVHS, ΔVLAS) and rate of change in the values per month (ΔVHS/month, ΔVLAS/month) were compared.ResultsAt the first visit, there were no significant differences in VLAS between the groups. At the median of 105 (interquartile ranges 83–155) days prior to the onset of CHF (group CHF) or the last visit (group no-CHF), VLAS was significantly higher in group CHF (mean, 2.9; standard deviation ± 0.4) than in group no-CHF (2.6 ± 0.3) (p = 0.028). ΔVLAS/month (area under the curve, 0.91; p<0.001) showed high diagnostic accuracy in distinguishing which dogs would develop CHF within 180 days and which would not.ConclusionsVLAS and ΔVLAS/month in dogs with pre-clinical MMVD may be useful to identify dogs at risk of developing CHF within the next 180 days.     

Total bilirubin is an independent predictor of death in dogs with degenerative valvular disease and dilated cardiomyopathy

IntroductionThere is little published regarding the association between canine cardiovascular disease and the hepatic system. The objective of the study was to evaluate the relationship between hepatic parameters, survival, and disease stages of dogs with either dilated cardiomyopathy (DCM) or degenerative valvular disease (DVD).Animals, materials, and methodsRetrospective study analyzing hepatic parameters in dogs with DVD or DCM in American College of Veterinary Internal Medicine stage B or C and healthy control dogs. Associations between liver parameters, type and stage of disease, and survival were investigated.ResultsNinety-nine dogs were included in the study: 61 DVD, 22 DCM, and 16 controls. Differences in liver parameter concentrations between DCM, DVD, and disease stages were found. Univariate analysis identified alanine aminotransferase (P < 0.001), aspartate aminotransferase (P = 0.02), and total bilirubin (P = 0.005) as predictors of mortality. In the multivariate analysis, total bilirubin remained an independent predictor of mortality.ConclusionsThe observed differences between DCM, DVD, and disease stages are likely consistent with disease-specific hemodynamics and progression of disease. This and the role of total bilirubin as an independent predictor for mortality indicate that in dogs with DVD and DCM the cardiovascular–hepatic interaction might be of relevance for disease progression and outcome, as reported for humans with cardiac disease. Further studies into the role of hepatic function in canine cardiac disease are required.     

Prospective study of dilated cardiomyopathy in dogs eating nontraditional or traditional diets and in dogs with subclinical cardiac abnormalities

BackgroundRecent studies have investigated dogs with presumed diet‐associated dilated cardiomyopathy (daDCM), but prospective studies of multiple breeds are needed.Hypothesis/ObjectivesTo evaluate baseline features and serial changes in echocardiography and cardiac biomarkers in dogs with DCM eating nontraditional diets (NTDs) or traditional diets (TDs), and in dogs with subclinical cardiac abnormalities (SCA) eating NTD.AnimalsSixty dogs with DCM (NTD, n = 51; TDs, n = 9) and 16 dogs with SCA eating NTDs.MethodsEchocardiography, electrocardiography, and measurement of taurine, cardiac troponin I, and N‐terminal pro‐B‐type natriuretic peptide were performed in dogs with DCM or SCA. Diets were changed for all dogs, taurine was supplemented in most, and echocardiography and cardiac biomarkers were reassessed (3, 6, and 9 months).ResultsAt enrollment, there were few differences between dogs with DCM eating NTDs or TDs; none had low plasma or whole blood taurine concentrations. Improvement in fractional shortening over time was significantly associated with previous consumption of a NTD, even after adjustment for other variables (P = .005). Median survival time for dogs with DCM was 611 days (range, 2‐940 days) for the NTD group and 161 days (range, 12‐669 days) for the TD group (P = .21). Sudden death was the most common cause of death in both diet groups. Dogs with SCA also had significant echocardiographic improvements over time.Conclusions and Clinical ImportanceDogs with DCM or SCA previously eating NTDs had small, yet significant improvements in echocardiographic parameters after diet changes.     

The outcome of surgical mitral valve repair with loop-in-loop technique in dogs with different stage myxomatous mitral valve disease

ObjectivesSurgical mitral valve repair is a possible option for dogs with myxomatous mitral valve disease. However, information on surgical results and postoperative echocardiography is limited. This study aimed to verify the stage-specific surgical results of mitral valve repair and postoperative echocardiographic changes for two years following surgery.AnimalsAdult dogs (n = 55) treated with surgical mitral valve repair using the loop-in-loop technique were included in this study. Medical records were retrospectively reviewed.ResultsNinety percent of cases (50/55) survived to discharge, which survival was significantly decreased in myxomatous mitral valve disease advanced-stage dogs, Stage B2 (n = 14): 100%, Stage C (n = 27): 96.2%, and Stage D (n = 14): 71.4%. Significant reductions of overall heart size (vertebral heart score: preoperative 11.4 vs. post one month 10.2, P < 0.001), left atrium (left atrium to aortic root ratio: preoperative 2.3 vs. post one month 1.5, P < 0.001) and left ventricle (left ventricular end-diastolic diameter [normalized for bodyweight]: preoperative 2.2 vs. post one month 1.5, P < 0.001) were documented one month after surgery, showing successful management of mitral regurgitation. All medications for mitral valve disease were discontinued three months after surgery. The recurrence of mitral regurgitation was not evident during the two-year follow-up period.ConclusionsSurgical mitral valve repair with the loop-in-loop technique is associated with significant decreases in indices of cardiac size at one-month post-repair. Disease stage influences operative survival after surgical mitral valve repair.     

Chronic hepatitis in Doberman pinschers. A review

Summary

Chronic hepatitis in Doberman pinschers is predominantly seen in female dogs, usually between 4 and 7 years of age and was first recognized in the early eighties. The histopathological characteristics of Doberman hepatitis are those of micronodular cirrhosis with histological features of fibrosis, piece meal necrosis and progressive lymphocyte and plasma cell infiltration of the portal triads. Currently there are two hypotheses on the pathogenesis although neither of them has been elucidated. The first hypothesis is that of a copper toxicosis. The second is that of autoimmunity. Similarities and differences with other breeds and studies on both hypotheses are reviewed, as well as results of recent research of our group. Based on recent findings chronic hepatitis in Doberman pinschers is most likely to be a form of copper toxicosis. Although there are several indications that suggest autoimmunity as well, this still remains unclear.     

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).

Effect of severity of myocardial failure on heart rate variability in Doberman pinschers with and without echocardiographic evidence of dilated cardiomyopathy.

OBJECTIVE: To determine whether heart rate variability (HRV) is reduced in Doberman Pinschers with dilated cardiomyopathy. DESIGN: Case series. ANIMALS: 62 overtly healthy Doberman pinschers. PROCEDURE: Heart rate variability was analyzed in time and frequency domains from data obtained during 24-hour ambulatory electrocardiographic Holter recordings in 41 overtly healthy Doberman pinschers with normal echocardiograms and 21 overtly healthy Doberman pinschers with abnormal echocardiograms. RESULTS: Heart rate variability usually was greater during night versus day, and 2 dogs with the most severe myocardial failure had reduced HRV. CONCLUSIONS AND CLINICAL RELEVANCE: Reduced HRV was detected only in Doberman Pinschers with the most severe myocardial failure. Thus, HRV in less severely affected dogs is not reduced, or the normal sinus arrhythmia of dogs renders HRV relatively insensitive. Analysis of HRV did not provide additional information relative to the severity of left ventricular dysfunction or risk of sudden death from that which could be derived from echocardiography, analysis of Holter recordings, and signal-averaged electrocardiography.     

Evaluation of the safety of daily administration of capromorelin in cats

Capromorelin is a ghrelin receptor agonist that is FDA approved for appetite stimulation in dogs. The objective of this study was to evaluate the safety of daily oral administration of capromorelin to cats over a range of doses and for an extended period. Two randomized, controlled studies were conducted: in Study 1, cats (n = 6 per group) received placebo or capromorelin at a dose of 9, 15, 30 or 60 mg/kg once daily for 14 days; and in Study 2, cats received capromorelin at 6 mg/kg (n = 8) or placebo (n = 4) once daily for 91 days. Cats were evaluated using clinical observations and clinical pathology test results for both studies, with the addition of postmortem examination in Study 1 and measurements of growth hormone and insulin‐like growth factor 1 in Study 2. Abnormal clinical observations were limited to emesis, hypersalivation, lethargy/depression, head shaking and lip smacking, which occurred more frequently in the capromorelin‐treated groups than in the placebo group. There were no clinically relevant differences in clinical pathology test results between the capromorelin and placebo groups in either study.     

Prevalence of Dilated Cardiomyopathy in Doberman Pinschers in Various Age Groups

Background: Dilated cardiomyopathy (DCM) in Doberman Pinschers is an autosomal dominant inherited disease. The prevalence of DCM in Doberman Pinschers of various age groups in Europe is currently unknown, but this information would be important to develop recommendations for screening programs. Objectives: To evaluate the prevalence of cardiomyopathy in various age groups of Dobermans. Animals: Seven hundred and seventy‐five examinations in 412 Doberman Pinschers. Methods: Dogs were included in a prospective longitudinal cohort study. Each examination included echocardiography and 24‐hour ECG (Holter) examination. A cut‐off value of >100 ventricular premature contractions (VPCs) per 24 hours on Holter examination or abnormal echocardiography was considered diagnostic for cardiomyopathy. The cumulative prevalence included all dogs with DCM and healthy dogs >7 years of age. Results: DCM prevalence in various age groups was as follows: age group 1 (1 to <2 years) 3.3%, age group 2 (2 to <4 years) 9.9%, age group 3 (4 to <6 years) 12.5%, age group 4 (6 to <8 years) 43.6%, and age group 5 (>8 years) 44.1%. The cumulative prevalence of Doberman Pinscher cardiomyopathy was 58.2%. There was an equal sex distribution, but male dogs showed earlier echocardiographic changes than did female dogs, which had significantly more VPCs. Conclusions and Clinical Importance: The prevalence of Doberman cardiomyopathy is very high in Europe. Disease manifestation and progression are different between male and female dogs. Yearly screening for DCM by Holter examination and echocardiography is recommended, starting at 2 years of age.     

Maternal chitosan oligosaccharide intervention optimizes the production performance and health status of gilts and their offspring

Chitosan oligosaccharides (COS) are the hydrolyzed product of chitosan and have multifunctional health benefits. The objective of this study was to elucidate the effect of COS as a dietary supplement to gilts on their productivity and health and that of their litters. Gilts were randomly assigned to either a treatment (n = 30) or control group (n = 30). The treatment gilts were fed a standard dry sow ration supplemented with COS at 0.12 and 0.24 g/gilt per d during gestation and lactation, respectively, and the control group was fed the standard dry sow ration only. The body weight, reproductive performance, milk production and litter size for each gilt and body weight of corresponding litters were recorded. The serum immunoglobulins (IgA, IgG, IgM) and secretory immunoglobulin A (sIgA) concentrations of gilts and piglets and fecal sIgA concertation of gilts were measured by Enzyme-linked immunosorbent assay (ELISA). Our study showed that maternal COS supplementation 1) significantly increased gilt body weight in late pregnancy (P < 0.05), 2) significantly increased milk production of gilts at different stages (d 1, 3, 7 and 19) of lactation (P < 0.05), 3) significantly increased body weight gain of piglets at weaning (P < 0.05), 4) significantly increased the serum concentrations of IgM and sIgA in piglets, and sIgA in fecal sample of gilts (P < 0.05), and 5) tended to increase the pregnancy success rate (P > 0.05) in the treatment group compared to the control group. These results suggest that maternal COS intervention in gilts can improve gilt milk production, piglet pre-weaning growth and immunity parameters in both gilts and piglets.     

Dilated cardiomyopathy in cats: survey of veterinary cardiologists and retrospective evaluation of a possible association with diet

Introduction/objectivesThe objectives were to conduct a survey of cardiologists on their recent experiences with cats that have dilated cardiomyopathy (DCM) and to retrospectively review individual cases of feline DCM.Animals, materials and methodsPart one: A survey was distributed to cardiologists with questions regarding caseload and clinical management of cats with DCM diagnosed over the past two years. Part two: Cardiologists completing the survey were invited to submit data from cats recently diagnosed with DCM. Data on signalment, clinical signs, diet, echocardiographic measurements and outcome were recorded.ResultsPart one: From 52 completed surveys, many cardiologists responded that measuring and supplementing taurine and recommending a diet change in cats with DCM are common practices. Few (15%) cardiologists reported an increase in the number of feline DCM cases over the past two years, although some had cases that improved even if taurine deficiency was not present. Part two: Twenty of 37 (54%) cats ate low pea/lentil (low PL) diets, and 14/37 (38%) ate high PL diets at the time of diagnosis; three had incomplete diet information. Two of 13 cats (15%) in which taurine was measured had levels below the reference range. After adjusting for other variables, cats eating high PL diets that changed diets after diagnosis had a significantly longer survival time than that of cats eating high PL diets that did not change diets after diagnosis (P = 0.025).ConclusionsAdditional research is warranted to determine whether there could be a possible association between diet and DCM in cats.     

Adverse effects of a 10‐day course of ibuprofen in Holstein calves

Nonsteroidal anti‐inflammatory drugs (NSAIDs) are recommended for various conditions in cattle. Ibuprofen is an inexpensive short‐acting NSAID and is readily available in liquid formulation for administration to bottle‐fed calves. We compared the adverse effects of a 10‐day course of ibuprofen and placebo in 16 five‐ to six‐week‐old Holstein bull calves that were being treated for experimentally induced bovine respiratory syncytial virus infection. Ibuprofen was administered as a liquid in milk replacer at 30 mg/kg divided three times daily. We found an increased prevalence of abomasal ulceration 5 of 8 in the ibuprofen compared to placebo group 2 of 6 (P = NS). There was one (1 of 8) case of mild interstitial nephritis in the ibuprofen and none (0 of 8) in the placebo group (P = NS). Renal function as measured by serum BUN and creatinine levels was not different between groups; no animal demonstrated an increase in creatinine.     

Heart rate variability in the dog: is it too variable?

The purpose of the study was to evaluate resting heart rate variability (HRV) as a simple noninvasive screening test for early autonomic derangement, heralding the development of occult dilated cardiomyopathy (DCM). Time and frequency domain HRV parameters were evaluated in 32 healthy Doberman pinschers, as potential predictors of the development of occult DCM within the following year and correlated with plasma catecholamines, markers of sympathoexcitation. Ten Dobermans with occult DCM and 8 Dobermans with congestive heart failure (CHF) were positive controls. Seven of the 32 "healthy" dogs developed occult DCM over the course of the study. None of the HRV parameters were associated with the development of occcult DCM based on univariate logistic regression. In dogs who developed occult DCM, plasma norepinephrine (NE) was inversely correlated with % fractal power (r = -0.81, P = 0.05). In dogs with occult DCM (positive controls), plasma NE was inversely correlated with fractal power (r = -0.81, r = 0.03), total power (r = -0.08, P = 0.03), high frequency power (r = -0.75, P = 0.05) and the standard deviation of the RR (r = -0.83, P = 0.02). The great inherent variability of the test may have limited our ability to discriminate between physiologic and pathophysiologic data, rendering this methodology inadequate as a screening test for early occult DCM. However, the negative correlations of NE with various forms of spectral power in dogs with occult DCM suggests that early in the natural history of DCM, there is parasympathetic withdrawal. A reduction in the nonharmonic, fractal component may be the first recognizable abnormality in the power spectrum of dogs who will develop DCM.