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.     

Ability of a 5‐Minute Electrocardiography (ECG) for Predicting Arrhythmias in Doberman Pinschers with Cardiomyopathy in Comparison with a 24‐Hour Ambulatory ECG

Background: Ventricular premature contractions (VPCs) are common in the occult stage of cardiomyopathy in Doberman Pinschers. Although the gold standard for detecting arrhythmia is the 24‐hour ambulatory electrocardiography (ECG) (Holter), this method is more expensive, time‐consuming and often not as readily available as common ECG. Objectives: Comparison of 5‐minute ECGs with Holter examinations. Animals: Eight hundred and seventy‐five 5‐minute ECGs and Holter examinations of 431 Doberman Pinschers. Methods: Each examination included a 5‐minute ECG and Holter examination. A cut‐off value of >100 VPCs/24 hours using Holter was considered diagnostic for the presence of cardiomyopathy. Statistical evaluation included calculation of sensitivity, specificity, positive predictive value, and negative predictive value. Results: Holter examinations revealed >100 VPCs/24 hours in 204/875 examinations. At least 1 VPC during a 5‐minute ECG was detected in 131 (64.2%) of these 204 examinations. No VPCs were found in the 5‐minute ECG in 73 (35.8%) examinations of affected Doberman Pinschers. A 5‐minute ECG with at least 1 VPC as cut‐off had a sensitivity of 64.2%, a specificity of 96.7%, a positive predictive value of 85.6% and a negative predictive value of 89.9% for the presence of >100 VPCs/24 hours. Conclusions and Clinical Importance: A 5‐minute ECG is a rather insensitive method for detecting arrhythmias in Doberman Pinschers. However, the occurrence of at least 1 VPC in 5 minutes strongly warrants further examination of the dog, because specificity (96.7%) and positive predictive value (85.6%) are high and could suggest occult cardiomyopathy.     

Use of Simpson's Method of Disc to Detect Early Echocardiographic Changes in Doberman Pinschers with Dilated Cardiomyopathy

Background: M‐mode is the echocardiographic gold standard to diagnose dilated cardiomyopathy (DCM) in dogs, whereas Simpson's method of discs (SMOD) is the preferred method to detect echocardiographic evidence of disease in humans. Objectives: To establish reference values for SMOD and to compare those with M‐mode measurements. Animals: Nine hundred and sixty‐nine examinations of 471 Doberman Pinschers. Methods: Using a prospective longitudinal study design. Reference values for SMOD were established using 75 healthy Doberman Pinschers >8 years old with <50 ventricular premature contractions (VPCs) in 24 hours. The ability of the new SMOD cut‐off values, normalized to body surface area (BSA), for left ventricular end‐diastolic volume (LVEDV/BSA >95 mL/m²) and end‐systolic volume (LVESV/BSA > 55 mL/m²) to detect echocardiographic changes in Doberman Pinschers with DCM was compared with currently recommended M‐mode values. Dogs with elevated SMOD values but normal M‐mode measurements were followed‐up using a prospective longitudinal study design. Results: At the final examination 175 dogs were diagnosed with DCM according to both methods (M‐mode and SMOD). At previous examinations, M‐mode values were abnormal in 142 examinations only, whereas all 175 SMOD already had detected changes. Additionally, 19 of 154 dogs with >100 VPCs/24 hours and normal M‐mode values had abnormal SMOD measurement. Six dogs with increased SMOD measurements remained healthy at several follow‐up examinations (classified as false positive); in 24 dogs with increased SMOD measurements, no follow‐up examinations were available (classified as unclear). Conclusions and Clinical Importance: SMOD measurements are superior to M‐mode to detect early echocardiographic changes in Dobermans with occult DCM.     

Results of ambulatory electrocardiography in overtly healthy Doberman Pinschers with equivocal echocardiographic evidence of dilated cardiomyopathy

OBJECTIVE: To determine results of ambulatory electrocardiography in and outcome of overtly healthy Doberman Pinschers with equivocal echocardiographic evidence of dilated cardiomyopathy. DESIGN: Case series. ANIMALS: 44 overtly healthy (25 male, 19 female) Doberman Pinschers. PROCEDURE: 24-hour ambulatory electrocardiographic (Holter) recordings with > 90% scan quality obtained the same day that echocardiography was performed were reviewed. RESULTS: Holter recordings from 42 of 44 (95%) dogs contained ventricular premature complexes (VPC). Fifteen of 44 (34%) dogs had > 100 VPC, 9 (20%) had > 500 VPC, and 5 (11%) had > 1,000 VPC. Nonsustained (< 30 seconds) ventricular tachycardia was detected in 4 dogs. Eighteen of 27 (67%) dogs with > 100 VPC, any couplets or triplets of VPC, or ventricular tachycardia developed dilated cardiomyopathy within 1 year, compared with 8 of 17 (47%) dogs with < 100 VPC, no couplets or triplets of VPC, and no ventricular tachycardia. Of the 18 dogs that did not develop dilated cardiomyopathy within 1 year, 11 (61%) did so within 3 years. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that a high percentage of Doberman Pinschers with equivocal echocardiographic evidence of dilated cardiomyopathy will be found to have VPC during 24-hour ambulatory electrocardiography and that most will develop echocardiographic abnormalities indicative of cardiomyopathy.     

Results of ambulatory electrocardiography in overtly healthy Doberman Pinschers with echocardiographic abnormalities

OBJECTIVE: To identify, by means of 24-hour ambulatory electrocardiography, electrocardiographic abnormalities in overtly healthy Doberman Pinschers in which results of echocardiography were abnormal. DESIGN: Clinical case series. ANIMALS: 56 (35 male, 21 female) overtly healthy Doberman Pinschers with echocardiographic evidence of cardiomyopathy on initial examination that subsequently died of cardiomyopathy. PROCEDURE: Twenty-four-hour ambulatory electrocardiographic (Holter) recordings obtained at the time of initial examination were reviewed. For all dogs, scan quality was > 90%. RESULTS: Initial Holter recordings of all 56 dogs contained ventricular premature contractions (VPC). Thirty-six (65%) dogs had > 1,000 VPC/24 h, 17 (31%) had > 5,000 VPC/24 h, and 11 (19%) had > 10,000 VPC/24 h. Fifty-four (96%) dogs had couplets of VPC, 37 (66%) had triplets of VPC, and 36 (64%) had episodes of nonsustained (< 30 seconds) ventricular tachycardia. Number of VPC/24 h during the initial Holter recordings was positively correlated with numbers of couplets and triplets of VPC and number of ventricular escape beats and negatively correlated with left ventricular fractional shortening. Twenty-eight dogs died suddenly prior to the putative onset of congestive heart failure. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that along with echocardiography, 24-hour ambulatory electrocardiography can be used to help identify overtly healthy Doberman Pinschers with cardiomyopathy.     

Association between results of ambulatory electrocardiography and development of cardiomyopathy during long-term follow-up of Doberman pinschers

OBJECTIVE: To characterize ambulatory electrocardiographic results of overtly healthy Doberman Pinschers and determine associations between those results and development of dilated cardiomyopathy. DESIGN: Cohort study. ANIMALS: 114 (58 male, 56 female) overtly healthy Doberman Pinschers without echocardiographic evidence of cardiac disease on initial examination. PROCEDURE: Echocardiograms and 24-hour ambulatory electrocardiograms (Holter recordings) were obtained initially and at variable intervals. The status (live vs dead) of all dogs was known at least 2 years and as long as 10 years after initial examination (mean [+/- SD] follow-up time, 4.33 +/- 1.84 years). Associations between development of dilated cardiomyopathy and number of ventricular premature contractions (VPC), age, and sex were determined. RESULTS: 55 dogs (48%) did not have VPC on initial Holter recordings, and only 8 dogs had > 50 VPC/24 hours. The likelihood that a dog would have VPC was associated with increasing age and being male. At least 1 VPC/24 hours, and in particular, > 50 VPC/24 hours or > or = 1 couplet or triplet of VPC/24 hours, were predictive of subsequent development of dilated cardiomyopathy. Fifty-four dogs (47%) developed dilated cardiomyopathy; 12 were still alive at the end of the study, and 42 had died. Twenty-five of these 42 dogs died after the onset of congestive heart failure (CHF), 15 died suddenly before the onset of overt CHF, and 2 died of noncardiac causes. More males developed dilated cardiomyopathy than females, and dogs that died suddenly were approximately 1 year younger than those that developed CHF. CONCLUSIONS AND CLINICAL RELEVANCE: Results of high-quality Holter recordings may be used to identify overtly healthy Doberman Pinschers that are at a high risk for dilated cardiomyopathy.     

European Society of Veterinary Cardiology screening guidelines for dilated cardiomyopathy in Doberman Pinschers

Background

Dilated cardiomyopathy (DCM) is the most common cardiac disease in large breed dogs and is inherited in Doberman Pinschers with a high prevalence (58%).

Toxicity in Doberman Pinchers with Ventricular Arrhythmias Treated with Amiodarone (1996–2005)

Background: Asymptomatic Doberman Pinschers with dilated cardiomyopathy (DCM) often die suddenly owing to ventricular tachycardia that degenerates into ventricular fibrillation. A safe and effective antiarrhythmic drug treatment is needed. This will require a large, well-controlled, prospective study.
Hypothesis: Amiodarone toxicity is common in Dobermans with occult DCM and ventricular tachyarrhythmias refractory to antiarrhythmia therapy. Infrequent monitoring of hepatic function is inadequate. Frequent monitoring may be useful to determine dogs in which the dosage should be decreased or the drug withdrawn.
Methods: Medical records from the University of Georgia and Cornell University were searched for Doberman Pinschers diagnosed with preclinical DCM that received amiodarone for severe ventricular arrhythmias refractory to other antiarrhythmic agents. Echocardiographic data, Holter recording data, hepatic enzyme serum activity, and serum amiodarone concentrations were recorded. The presence of clinical signs of toxicity was recorded. Serum amiodarone concentrations were obtained in some dogs.
Results: Reversible toxicity was identified in 10 of 22 (45%) dogs.
Conclusion and Clinical Importance: Adverse effects from amiodarone were common and were, in part, dosage related. Patients should be monitored for signs of toxicity and liver enzyme activity should be measured at least monthly.     

Histologic characterization of canine dilated cardiomyopathy

Dilated cardiomyopathy (DCM), characterized by chamber dilatation and myocardial systolic and diastolic dysfunction, is one of the most common heart diseases in dogs. The clinical diagnosis is based on findings on echocardiographic and Doppler examinations, with the active exclusion of other acquired or congenital heart diseases. However, the echocardiographic criteria for the diagnosis of DCM are not wholly specific for the disease, and histologic examination may be necessary for final diagnosis. Review of reports on histologic findings in dogs with clinically diagnosed DCM reveals two histologically distinct forms of DCM: 1) cardiomyopathy of Boxers and 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, classified as the "attenuated wavy fiber" type of DCM. The histologic changes of the attenuated wavy fiber type of DCM may precede clinical and echocardiographic signs of heart disease, thus indicating an early stage of DCM.     

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.     

Evaluation of the cardiac actin gene in Doberman Pinschers with dilated cardiomyopathy

OBJECTIVE: To evaluate the coding region of the cardiac actin gene in Doberman Pinschers with dilated cardiomyopathy (DCM) for mutations that could be responsible for the development of the condition ANIMALS: 28 dogs (16 Doberman Pinschers with DCM and 12 mixed-breed control dogs). PROCEDURE: Ten milliliters of blood was collected from each dog for DNA extraction. Polymerase chain reaction (PCR) primers were designed to amplify canine exonic regions, using the sequences of exons 2 to 6 of the cardiac actin gene. Single-stranded conformational polymorphism analysis was performed for each exon with all samples. Autoradiographs were analyzed for banding patterns specific to affected dogs. The DNA sequencing was performed on a selected group of affected and control dogs. RESULTS: Molecular analysis of exons 2 to 6 of the cardiac actin gene did not reveal any differences in base pairs between affected dogs and control dogs selected for DNA evaluation. CONCLUSIONS: Mutations in exons 5 and 6 of the cardiac actin gene that have been reported in humans with familial DCM do not appear to be the cause of familial DCM in Doberman Pinschers. Additionally, evaluation of exons 2 to 6 for causative mutations did not reveal a cause for inherited DCM in these Doberman Pinschers. Although there is evidence that DCM in Doberman Pinschers is an inherited problem, a molecular basis for this condition remains unresolved. Evaluation of other genes coding for cytoskeletal proteins is warranted.     

Plasma fatty acid concentrations in Boxers and Doberman Pinschers

OBJECTIVE: To compare plasma fatty acid concentrations and the relationships of fatty acids to arrhythmias in Boxers versus Doberman Pinschers. ANIMALS: 38 Boxers and 13 Doberman Pinschers. PROCEDURES: Boxers and Doberman Pinschers evaluated via Holter recording and for which a blood sample was available were included. Echocardiograms were performed in 49 of 51 dogs. The number of ventricular premature complexes (VPCs)/24 h was counted and fatty acids analyzed. Plasma fatty acid concentrations and VPCs/24 h, as well as correlations between the 2 variables, were compared between the 2 breeds. RESULTS: Compared with the Doberman Pinschers, Boxers had significantly higher plasma concentrations of gamma-linolenic acid but lower concentrations of arachidonic acid. Total n-6 fatty acids and total polyunsaturated fatty acid concentrations were higher in Doberman Pinschers. There were significant, but weak, positive correlations between VPCs and oleic acid, total n-3 fatty acids, and total n-9 fatty acids in Boxers but not in Doberman Pinschers. CONCLUSIONS AND CLINICAL RELEVANCE: Data suggested that plasma fatty acid concentrations may differ between Boxers and Doberman Pinschers and that the relationship between fatty acid concentrations and VPCs may be different between these 2 breeds.     

Evaluation of the phospholamban gene in purebred large-breed dogs with dilated cardiomyopathy

OBJECTIVE: To evaluate the role of the phospholamban gene in purebred large-breed dogs with dilated cardiomyopathy (DCM). ANIMALS: 6 dogs with DCM, including 2 Doberman Pinschers, 2 Newfoundlands, and 2 Great Danes. PROCEDURE: All dogs had clinical signs of congestive heart failure, and a diagnosis of DCM was made on the basis of echocardiographic findings. Blood samples were collected from each dog, and genomic DNA was isolated by a salt extraction method. Specific oligonucleotides were designed to amplify the promoter, exon 1, the 5'-part of exon 2 including the complete coding region, and part of intron 1 of the canine phospholamban gene via polymerase chain reaction procedures. These regions were screened for mutations in DNA obtained from the 6 dogs with DCM. RESULTS: No mutations were identified in the promoter, 5' untranslated region, part of intron 1, part of the 3' untranslated region, and the complete coding region of the phospholamban gene in dogs with DCM. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicate that mutations in the phospholamban gene are not a frequent cause of DCM in Doberman Pinschers, Newfoundlands, and Great Danes.     

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).

Molecular evaluation of five cardiac genes in Doberman Pinschers with dilated cardiomyopathy

OBJECTIVE: To sequence the exonic and splice site regions of 5 cardiac genes associated with the human form of familial dilated cardiomyopathy (DCM) in Doberman Pinschers with DCM and to identify a causative mutation. ANIMALS: 5 unrelated Doberman Pinschers with DCM and 2 unaffected Labrador Retrievers (control dogs). PROCEDURES: Exonic and splice site regions of the 5 genes encoding the cardiac proteins troponin C, lamin A/C, cysteine- and glycine-rich protein 3, cardiac troponin T, and the beta-myosin heavy chain were sequenced. Sequences were compared for nucleotide changes between affected dogs and the published canine sequences and 2 control dogs. Base pair changes were considered to be causative for DCM if they were present in an affected dog but not in the control dogs or published sequences and if they involved a conserved amino acid and changed that amino acid to a different polarity, acid-base status, or structure. RESULTS: A causative mutation for DCM in Doberman Pinschers was not identified, although single nucleotide polymorphisms were detected in some dogs in the cysteine- and glycine-rich protein 3, beta-myosin heavy chain, and troponin T genes. CONCLUSIONS AND CLINICAL RELEVANCE: Mutations in 5 of the cardiac genes associated with the development of DCM in humans did not appear to be causative for DCM in Doberman Pinschers. Continued evaluation of additional candidate genes or a focused approach with an association analysis is warranted to elucidate the molecular cause of this important cardiac disease in Doberman Pinschers.     

Heart rate variability in Doberman Pinschers with and without echocardiographic evidence of dilated cardiomyopathy

OBJECTIVE: To characterize the salient variables of the time-domain analysis of heart rate variability (HRV) in clinically normal Doberman Pinschers and to compare those variables with those of Doberman Pinschers with cardiomyopathy and mild to moderate myocardial failure. ANIMALS: 46 Doberman Pinschers. PROCEDURE: HRV was analyzed in the time-domain from 24-hour Holter recordings obtained from 28 Doberman Pinschers with normal echocardiograms and 18 Doberman Pinschers with echocardiograms consistent with mild to moderate myocardial failure. RESULTS: Significant differences in HRV variables between the 2 groups of dogs were not detected. The HRV was greater during the nighttime (12 AM to 6 AM), compared with the 24-hour day and an 18-hour (6 AM to 12 AM) period. CONCLUSIONS AND CLINICAL RELEVANCE: HRV of dogs with mild to moderate myocardial failure was not different from that of clinically normal dogs, because there were no disturbances of autonomic balance, baroreceptor function, and other factors that influence HRV in the dogs with cardiomyopathy, or the sensitivity of time-domain analysis was overwhelmed by normal sinus arrhythmia. The techniques now used to study HRV have important limitations, especially in dogs, and better noninvasive tests of autonomic function are needed.     

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.     

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.     

Efficacy of Benazepril Hydrochloride to Delay the Progression of Occult Dilated Cardiomyopathy in Doberman Pinschers

Background: Angiotensin converting enzyme inhibitors (ACEIs) are recommended in people to treat asymptomatic (occult) dilated cardiomyopathy (DCM). Efficacy of therapy in occult DCM in dogs is unknown.
Hypothesis: ACEIs, specifically benazepril hydrochloride (BH), will delay the onset of overt DCM in Doberman Pinschers.
Animals: Ninety-one Doberman Pinschers were studied, 57 dogs received BH, and 34 dogs no ACEI.
Methods: Retrospective study of the medical records of all Doberman Pinschers with occult DCM that received BH or no ACEI between April 1989 and February 2003. Two criteria of left ventricular enlargement were used for enrollment: one independent of body weight (BW) (C1) and the other indexed to BW (C2). Cox proportional hazards analyses were used to identify variables associated with the onset of overt DCM.
Results: On univariate analysis the median time to onset of overt DCM was significantly longer for the benazepril group (for C1: 425 days for BH, 95% confidence interval [CI] 264–625 days; 339 days for no ACEI, CI 172–453 days, P = .02; for C2: 454 days for BH, CI 264–628 days; 356 days for no ACEI, CI 181–547 days, P = .02). The hazard ratio (HR) (benazepril/no ACEI) was 0.57, CI 0.35–0.94, P = .03 for C1; HR = 0.56, CI 0.34–0.93, P = .02 for C2. On multivariate analysis, BH significantly delayed onset of overt DCM (HR [benazepril/no ACEI] = 0.45, CI 0.26–0.78, P < .01, for C1; HR = 0.36, CI 0.21–0.63, P < .01, for C2).
Conclusions: BH in particular and ACEIs in general might delay the progression of occult DCM. Prospective studies are warranted to test this theory.     

Resting and Dobutamine Stress Echocardiographic Factors Associated with the Development of Occult Dilated Cardiomyopathy in Healthy Doberman Pinscher Dogs

In 29 healthy Doberman Pinschers, echocardiographic parameters evaluating systolic and diastolic function were examined prospectively at rest and during dobutamine constant rate infusion (5 μg/kg/minute) to determine if any parameters were associated with the development of occult dilated cardiomyopathy (DCM). A resting echocardiogram was repeated 1 year later to determine which dogs had met our criteria for occult DCM. Six dogs developed occult DCM during the follow-up period. Univariate logistic regression analysis showed that at rest, an increased left ventricular internal dimension in systole (LVID-S) ( P = .02), preejection period (PEP) ( P = .03), ratio of PEP to left ventricular ejection time ( P = .02), and isovolumic relaxation time ( P = .02) were significantly associated with the development of occult DCM. During dobutamine stress echocardiography (DSE), high LVID-S ( P = .02) and systolic wall stress index ( P = .04) and reduced fractional shortening ( P = .02) and ratio of peak early to late diastolic mitral filling velocity (E/A) ( P = .05) were associated with the development of occult DCM. Multiple logistic regression showed that LVID-S ( P = .002) and E/A ( P = .002) measured during dobutamine infusion also were associated with the development of occult DCM. Reclassification based on the DSE data was not significantly different than reclassification based on the resting echocardiographic data. Resting echocardiography and DSE have the potential to be clinically applicable screening tests for very early systolic and diastolic dysfunction in Doberman Pinschers, heralding the onset of occult DCM as it is currently defined.