Dilated Cardiomyopathy in Standard Schnauzers: Retrospective Study of 15 Cases
ABSTRACT
Dilated cardiomyopathy (DCM) is the most common myocardial disorder of dogs, typically affecting large and giant breeds. The purpose of this study was to describe the clinical features of DCM in standard schnauzers. Medical records for 15 standard schnauzers diagnosed with DCM were reviewed. The median age at diagnosis of DCM was 1.6 yr, with all dogs developing left-sided congestive heart failure (CHF). The median age of onset of CHF was 1.6 yr, and was significantly shorter in males (1.5 yr) than for females (2.35 yr). The median survival time after diagnosis of CHF was 22 days, and was shorter in males (13 days) than females (62 days). The occurrence of early onset DCM in multiple closely related standard schnauzers suggests a familial predisposition in this breed. Pedigree analysis confirmed common ancestry for all DCM affected dogs with a most likely autosomal recessive mode of inheritance.
Introduction
Dilated cardiomyopathy (DCM) is the most common myocardial disease reported in dogs, and one of the most commonly acquired cardiovascular diseases overall. Dilated cardiomyopathy has been described in numerous breeds, including the Doberman pinscher, Great Dane, Newfoundland, cocker spaniel, boxer, Dalmatian, Portuguese water dog, and toy Manchester Terrier.1–13 In general, DCM typically progresses through two distinct stages. An asymptomatic stage, often referred to as the occult stage, describes dogs with no clinical signs that may have electrical or morphologic abnormalities detectable by conventional diagnostic testing. These dogs may eventually progress to the overt stage, in which clinical signs attributable to congestive heart failure (CHF) become apparent.14 Although all the aforementioned breeds share characteristic progressive left ventricular dilation and diminution in systolic function, the etiopathogenesis, clinical course, and response to treatment are variable.
Dilated cardiomyopathy in the standard schnauzer has been infrequently reported in the literature, and, to date, has not been evaluated as a breed-specific entity.15 The purpose of this study was to describe the clinical features of DCM in 15 standard schnauzers.
Materials and Methods
Case Selection
To identify DCM affected standard schnauzers for the study, owners were solicited via request through the Standard Schnauzer Club of America electronic mailing list. Clinical and historical information were obtained from examination of medical records and from communication with the breeders, dog owners, and attending veterinarians. Inclusion criteria consisted of a diagnosis of DCM via echocardiography or postmortem evaluation including both gross and histopathologic evaluation. An echocardiographic diagnosis of DCM was defined as evidence of a dilated left ventricle (increased left ventricular internal diameter in diastole and systole) with a reduced fractional shortening.16 As no breed-specific echocardiographic reference ranges have been established for standard schnauzers, reference ranges for left ventricular chamber measurements were based on previously published allometric scaling reference values and a fractional shortening <25% was considered abnormal.4,5,16–19 A postmortem diagnosis of DCM was defined as moderate to marked cardiomegaly with gross dilation of the left or all four heart chambers, microscopic evidence of myofiber attenuation and/or myofiber degeneration with fibrosis and/or adipose infiltration, and the absence of other significant gross or microscopic cardiac pathology.18,20
Clinical Findings
Medical records were evaluated for data regarding gender, age at DCM diagnosis, age at CHF diagnosis, clinical presentation, diagnostic testing results (electrocardiography, echocardiography, radiography, biochemistry, histopathology), and date and cause of death. CHF was defined as either the presence of ascites or pleural effusion and/or radiographic evidence of cardiogenic pulmonary edema. Cardiac-related deaths included euthanasia directly attributed to underlying cardiac disease and sudden death in which there were no preceding clinical signs and no apparent underlying cause could be identified.
Pedigree Analysis
Pedigrees from all affected dogs were collected and assembled using commercially available pedigree analysis softwarea. Additionally, owners and breeders were questioned about a history of heart disease and the current health status of the parents, siblings, or offspring of affected dogs. Dogs that died suddenly at an early age (<3 yr of age) with no obvious cause were included in pedigree analysis, but not in the clinical evaluation. Dogs were considered to be phenotypically normal on the basis of either a normal echocardiographic screening and/or survival into late adulthood (>7 yr of age) without clinical evidence of cardiac disease. Pedigrees were evaluated to determine if an autosomal, sex-linked, or mitochondrial mode of inheritance pattern could be identified as described elsewhere.21,22
Statistical Analysis
Descriptive statistics for age were assessed for normality by assessment of error residuals via a Shapiro-Wilk test. An analysis of variance was then used to determine gender differences in age. Categorical variables were analyzed by a Chi-squared analysis. To assess onset of CHF and survival time (onset of CHF to death), genders were compared using Kaplan-Meier product-limit estimates followed by a log-rank test for significance. All analyses were conducted using a commercial software packageb. A type one error probability of <0.05 was considered significant.
Results
Clinical Findings
Fifteen standard schnauzers were identified that met the inclusion criteria for a diagnosis of DCM (numbers 1–15 in Table 1). Ten dogs were included on the basis of echocardiography, one via postmortem evaluation, and four with both echocardiographic and postmortem evaluation. Of these dogs, four were sexually intact males, three were castrated males, six were sexually intact females, and two were spayed females. The age at diagnosis of DCM ranged from 0.9 to 2.8 yr (mean ± SD, 1.8 ± 0.7 yr; median, 1.6 yr), and the average age of males (1.54 yr) was not significantly different (P = 0.09) than females (1.97 yr). In this population, 11 of 15 dogs (73%) were diagnosed concurrently with left-sided CHF via thoracic radiography upon initial diagnosis (i.e., overt DCM). Four of 15 dogs (27%) were originally diagnosed with occult DCM (numbers 2, 3, 5, and 7). The dogs diagnosed with occult DCM initially were evaluated because of the recent diagnosis of DCM and CHF in a sibling (n = 2), unexplained sudden death in a sibling (n = 1), or both (n = 1). All four dogs diagnosed initially with occult DCM were prescribed medications including enalapril (n = 4), carvedilol (n = 3), pimobendan (n = 1), and digoxin (n = 1). All dogs initially diagnosed with occult DCM subsequently developed clinical and radiographic findings of left-sided CHF within 0.25–3.17 yr.
CM, castrated male; DCM, dilated cardiomyopathy; E, euthanasia; M, male; F, female; SF, spayed female; SD, sudden death.
Dogs with the same superscript letters are littermates.
For the 11 dogs initially presenting with symptoms, the most common historical complaints included increased respiratory rate and effort (n = 10), coughing (n = 10), exercise intolerance (n = 9), decreased appetite (n= 6), syncope (n = 1), and pale mucous membranes (n = 1). Auscultatory abnormalities detected during physical examination included low to moderate intensity (grade 1 to 3/6) left apical systolic murmurs (n = 6), crackles (n = 5), a gallop sound (n = 1), and an unspecified arrhythmia (n = 1).
Electrocardiographic examinations were performed in two dogs during the occult phase and revealed a normal sinus rhythm in one dog and a sinus arrhythmia, 1st and 2nd degree atrioventricular block, and occasional ventricular premature complexes in the other dog. An atropine response test was performed and the sinus arrhythmia and atrioventricular block resolved. Electrocardiographic recordings were performed in 11 dogs with overt DCM documenting a sinus tachycardia (n = 8), normal sinus rhythm (n = 2), a left bundle branch block (n = 1), and ventricular premature complexes (n = 2). In one of the cases, the ventricular ectopy was deemed by the attending cardiologist to require anti-arrhythmic therapy with mexiletine. In addition to radiographic signs consistent with left-sided CHF, pleural effusion was noted in three dogs suggestive of biventricular failure. Echocardiographic examinations were performed in 14 dogs (numbers 1–11 and 13–15). Echocardiographic examinations were performed by a combination of board certified cardiologists (n = 11), internists (n = 2), and an experienced veterinary ultrasonographer (n =1). Echocardiography revealed severe left ventricular dilation in diastole and systole and a decreased fractional shortening (Tables 2, 3). Two dogs were diagnosed with moderate pulmonary hypertension. Repeat echocardiographic examinations were available in four dogs revealing progressive increases in both the left ventricular end-systolic and diastolic diameters. Four dogs had plasma and/or whole blood plasma taurine concentrations evaluated upon diagnosis, prior to any taurine supplementation. Plasma taurine concentrations were evaluated in three dogs (numbers 6, 7, and 9) and were 190, 62, and 190 nmol/mL, respectively (reference range 60–120 nmol/mL). Whole blood taurine concentrations were evaluated in two dogs (numbers 9 and 13) and were 431 and 860 nmol/mL, respectively (reference range 200–350 nmol/mL). Cardiac troponin-I concentrations were assessed in two dogs and were minimally increased at 0.1 ng/mL (reference range, <0.6 ng/mL) and 0.17 ng/mL (reference range, <0.05 ng/mL), respectively.
FS, fractional shortening; LVIDd, left ventricular internal diameter at end-diastole; LVIDs, left ventricular internal diameter at end-systole.
FS, fractional shortening; LVIDd, left ventricular internal diameter at end-diastole; LVIDs, left ventricular internal diameter at end-systole.
Four dogs were euthanized upon the initial diagnosis of CHF (numbers 4, 10, 12, and 15). Standard medical therapy for CHF was instituted for the remaining 11 dogs with a variable combination and dosage of furosemide (n = 11), enalapril (n = 9), pimobendan (n = 8), spironolactone (n = 3), and digoxin (n = 1). Six of the 11 dogs (55%) were supplemented with taurine and L-carnitine. Recheck echocardiographic examinations were performed in two of the six dogs receiving taurine and L-carnitine supplementation and revealed no improvement in myocardial systolic function. The cause of death was attributed to cardiac disease in all cases. Euthanasia was the most common cause of death, occurring in 13 of 15 dogs (87%), while sudden death occurred in 2 of 15 dogs (13%). Owners indicated that humane euthanasia was elected for a combination of reasons including veterinary assessment of a poor prognosis (n = 9), quality-of-life concerns (n = 8), lack of response to treatment (n = 4), and cost (n = 1).
Survival Analysis
The median (25th–75th interquartile range [IQR]) age at onset of CHF was 1.6 yr (1.25–2.84 yr), and ranged from 0.86 to 5.74 yr. The age of onset of CHF was significantly (P = 0.0384) earlier for male dogs (1.5 yr, IQR 1.07–2.25 yr) than for female dogs (2.35 yr, IQR 1.49–3.48 yr) (Figure 1). The median survival time (from onset of CHF to death from all causes) was 22 days (0–70 days) and ranged from 10–182 days. The median survival time was significantly (P = 0.0232) shorter for male dogs (13 days, IQR 0–22 days) than female dogs (62 days, IQR 31–110 days) (Figure 2). The median age at death for all dogs was 1.6 yr (1.25–2.84 yr), ranging from 0.86–6.11 yr (Table 1).
Citation: Journal of the American Animal Hospital Association 53, 1; 10.5326/JAAHA-MS-6506
Citation: Journal of the American Animal Hospital Association 53, 1; 10.5326/JAAHA-MS-6506
Postmortem Findings
Postmortem evaluations were performed in five dogs (numbers 9–13). Postmortem examinations were performed by board certified veterinary pathologists from four different institutions. Moderate to marked cardiomegaly with biventricular dilation was described in all dogs on gross examination. Two of the reports provided data on the heart weight and heart weight to body weight ratio. The heart weights were 166 and 147 g, respectively. The heart weight to body weight ratios were increased at 9.5 and 9 g/kg, respectively (reference range 6.3–6.9 g/kg).23 Histopathology was performed in all five cases with sections of the right ventricular free wall, interventricular septum, and left ventricular free wall. Histopathologic abnormalities of the left ventricle and interventricular septum included: myocyte degeneration (n = 4), increased interstitial fibrosis (n = 3), myocyte attenuation (n = 3), fatty myocardial infiltration (n = 2), interstitial myocardial edema (n = 2), and myocyte necrosis (n = 1). Reported histopathologic abnormalities within sections of the right ventricle included: myocyte degeneration (n = 2), myocyte attenuation (n = 2), mild to moderate fatty myocardial infiltration (n = 2), and myocyte necrosis (n =1). Additional histopathology of sections of the left and right atria were performed in four cases revealing myocyte degeneration and fibrosis (n = 2), myocyte attenuation (n = 1), and myocyte necrosis (n = 1). No evidence of myocardial inflammation or infectious endocarditis was identified in any animal. Four cardiac specimens were evaluated with attached lung specimens, revealing evidence of cardiogenic pulmonary edema in each case. Liver specimens were evaluated in three cases, revealing varying degrees of hepatic congestion in each case.
Pedigree Analysis
Pedigrees for all 15 confirmed cases (numbers 1–15) as well as two siblings (numbers 16–17) that died suddenly without symptoms at an early age were assembled and analyzed to determine a mode of inheritance (Table 1). The geographic distribution of affected dogs was wide, spanning over 12 states in the United States. Analysis of the pedigree revealed all dogs were related, having common ancestry within a maximum of nine generations. Specific relationships identified included five sets of affected full siblings (numbers 1–3; numbers 4 and 5; numbers 6, 7, and 16; numbers 8 and 17; and numbers 9 and 10), one set of affected half siblings with the same sire (numbers 12 and 13), several half-avuncular pairs (numbers 4 and 5 were half aunt and half uncle, respectively, of numbers 12 and 13), a full-avuncular pair (number 14 was full aunt of number 15), and first cousins (number 11 was a first cousin to numbers 9 and 10) (Table 1). All affected dogs were offspring of phenotypically normal parents, both males and females were equally affected, and generation skipping was noted since one affected female dog had a litter of dogs that were all phenotypically normal as adults (Figure 3). These findings rule out simple autosomal dominant, X-linked, and mitochondrial modes of inheritance. An autosomal recessive mode of transmission is considered most likely, although more complex modes, such as polygenic or autosomal dominance with reduce penetrance, cannot be excluded.
Citation: Journal of the American Animal Hospital Association 53, 1; 10.5326/JAAHA-MS-6506
Discussion
Based on the results of our study, DCM in standard schnauzers is characterized by the development of left-sided CHF in early adulthood. The age of onset appears unique to this breed as the standard schnauzers tended to be older than reported toy Manchester Terriers and Portuguese water dogs, but much younger than the majority of larger breeds.1,4,5,10–13 No sex predisposition could be identified in this population of animals, though female dogs developed CHF later than male dogs and female dogs survived longer than male dogs once they developed CHF. In the Doberman pinscher, males have been reported to be overrepresented in comparison to females, although the difference in gender prevalence is less than previously thought.24 However, analysis of a larger population may identify a sex predisposition in the standard schnauzer breed.
The presence of documented arrhythmias in this population was low (14%) compared to previous studies of DCM in dogs; however, in the absence of Holter monitor examinations, paroxysmal arrhythmias were possible.15 The dogs that died suddenly were not reported to have had any arrhythmias, yet, with the absence of premonitory signs, a fatal dysrhythmia seems likely. Atrial fibrillation, commonly associated with DCM in large and giant breed dogs, was not diagnosed in any of the dogs of this report.4,5,25–27
The similar age of onset among highly related individuals from diverse geographical locations is strongly suggestive of a familial component. The hallmark features of an autosomal recessive trait were evident in this population, although more complex modes of inheritance cannot be ruled out. Inheritance patterns for DCM are variable among different breeds. The majority of studies report an autosomal dominant transmission in breeds such as Doberman pinschers, Irish wolfhounds, and Newfoundlands.28–30 An X-linked transmission has been reported in Great Danes and a mixed monogenic-polygenic model with sex dependent alleles has been described in Irish wolfhounds.4,31 An autosomal recessive inheritance has also been reported for Portuguese water dogs.11,12
Certain limitations are present in this study that should be considered. As a retrospective evaluation, we were limited by the varied reporting forms and medical records utilized by the attending veterinary clinicians, echosonographers, and pathologists. Additionally, not all of the dogs considered phenotypically normal had an echocardiographic evaluation. However, given the early age of onset and death of DCM affected dogs in this cohort, dogs that survived into late adulthood with no clinical signs of heart disease were likely not affected with this form of DCM.
Conclusion
Dilated cardiomyopathy appears to be familial in nature and early in onset in standard schnauzers. Results for dogs in this study suggest that CHF is a common sequela of DCM in standard schnauzers and carries a poor long-term prognosis. Dilated cardiomyopathy should be considered a differential in young standard schnauzer dogs diagnosed with CHF.
Kaplan-Meier product limit estimates demonstrating the age of onset of CHF in 15 standard schnauzer dogs with DCM. The median time to the onset of CHF was significantly shorter (P = 0.0384) for male dogs than for female dogs at 1.5 and 2.35 yr, respectively. CHF, congestive heart failure; DCM, dilated cardiomyopathy.
Kaplan-Meier product limit estimates of survival times (onset of CHF to date of death) in 15 standard schnauzer dogs with DCM. The median survival time was significantly shorter (P = 0.0232) for male dogs than for female dogs at 13 and 62 days, respectively. CHF, congestive heart failure; DCM, dilated cardiomyopathy.
Representative pedigrees from two subsets of related standard schnauzers with DCM. Circles are female dogs; squares are male dogs. A solid black symbol indicates that the dog was definitively diagnosed with DCM. Striped symbols indicate dogs with suspected DCM based on sudden death at a young age. A solid white symbol indicates that the dog was considered phenotypically normal on the basis of an echocardiogram and/or survival into late adulthood (>7 yr of age) without apparent clinical evidence of DCM. Symbols with a question mark identify dogs in which the phenotype is unknown due to lack of an echocardiogram and an age <7 yr. A diagonal line through the symbol indicates a deceased dog; a black dot to the inferior right of the symbol indicates dogs originally diagnosed with occult DCM. (*) Dogs that were evaluated with an echocardiogram. DCM, dilated cardiomyopathy.
Contributor Notes
