Vet Clin Small Anim

34 (2004) 1187–1207

Dilated cardiomyopathy: an update

Michael R. O’Grady, DVM, MS*,
M. Lynne O’Sullivan, DVM, DVSc
Department of Clinical Studies, University of Guelph, Guelph, Ontario, Canada

This review focuses on areas of somewhat recent discovery that relate in

large part to the areas studied or under investigation by the authors over the
last 10 years. Readers are referred to reviews of areas of discussion that do
not fall within this domain. We believe that cardiomyopathy of Boxers is
substantially different from the dilated cardiomyopathy (DCM) observed in
the ‘‘typical’’ giant-breed dog or Doberman Pinscher, such that a discussion
of cardiomyopathy as it occurs in the Boxer is dealt with elsewhere [1,2].

Definition
DCM is an important cause of cardiac morbidity and mortality in the
dog. Next to chronic mitral valve insufficiency (CMVI) and in some select
geographic regions where heartworm disease is common, DCM is the most
commonly acquired cardiac disorder in the dog.
The World Health Organization (WHO) and the International Society
and Federation of Cardiology (ISFC) have jointly championed the
classification of the cardiomyopathies. Dilated cardiomyopathy is the term
used to define the primary myocardial disorder characterized by reduced
contractility and ventricular dilation involving the left or both ventricles
of unknown or familial etiology. For cases with a specific cause for the
DCM, a modifier indicating this etiology precedes the term cardiomyopathy,
such as taurine deficiency cardiomyopathy.

This article was funded in part by Boehringer Ingelheim Animal Health Canada and
Novartis Animal Health Canada.
* Corresponding author.
E-mail address: mogrady@uoguelph.ca (M.R. O’Grady).

0195-5616/04/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.cvsm.2004.05.009
1188 M.R. O’Grady, M.L. O’Sullivan / Vet Clin Small Anim 34 (2004) 1187–1207

Etiology
DCM, as already defined, is a morphologic diagnosis. The heart has
a limited number of responses to many potential myocardial insults. Thus,
the morphologic response called DCM provides no insight as to the
myocardial insult(s) that contributed to this outcome. Idiopathic DCM is
the most common form of DCM in the dog, but most of the potential
processes causing myocardial insult in dogs remain to be determined. In
people, the most common causes of DCM include familial/genetic, viral or
immunologic, and toxic factors [3]. Recognized causes of DCM in the dog
include genetic factors, tachycardia, taurine deficiency, toxic factors, and,
possibly, carnitine deficiency. The reader is referred to several excellent
reviews of these various etiologies [4–6]. We wish to address the potential for
an immunologic or viral etiology. There is substantial evidence to support
an immunologic or viral etiology in some cases of DCM in people [3]. In the
veterinary world, Cobb et al [7] could not demonstrate evidence of abnormal
antimyocardial antibodies in a sample of dogs with DCM. Day [8] did
observe antimitochondrial antibodies in 30% of a colony of English Cocker
Spaniels with DCM, however. This study also observed a relation between
DCM and reduced IgA as well as complement component C4, which are
markers of immune disease in human beings. Braz-Ruivo [9] failed to
identify parvoviral DNA in myocardial samples of Doberman Pinschers
with DCM. He also investigated the role of an immunologic etiology by
measuring levels of antimyosin and antilaminin antibodies and circulating
immunoglobulin (IgG and IgM) in serum of affected Doberman Pinschers.
He failed to observe abnormalities in either area of investigation. These
findings do not exclude the possibility of an immunologic reaction directed
against other myocardial proteins, including contractile, regulatory, and
cytoskeletal matrix as well as extracellular matrix or membrane.

Natural history and prognosis

The natural history of DCM has not been studied in most breeds. Most
of the natural history data available concerning DCM applies to the
Doberman Pinscher. One needs to ask whether the clinical features, natural
course, and response to therapy as described for the Doberman Pinscher are
typical for other dogs that acquire DCM. It is presumed that DCM in other
breeds is modeled on that of the Doberman Pinscher, except that the
progression of DCM in the final stage (overt stage) is more rapid in the
Doberman Pinscher. The rate of progression of the occult stage in other
breeds compared with the Doberman Pinscher is undetermined.
The natural progression of DCM can be described by three distinct
stages/phases (Fig. 1). Stage I is characterized by a morphologically and
electrically normal heart and no evidence of clinical signs of heart disease.
Stage II is characterized by evidence of morphologic or electrical de-
 M.R. O’Grady, M.L. O’Sullivan / Vet Clin Small Anim 34 (2004) 1187–1207 1189

Fig. 1. A timeline of the natural history of dilated cardiomyopathy (DCM). Three stages
describe the progression to clinical signs of congestive heart failure caused by DCM.

rangement in the absence of clinical signs of heart disease. This stage has
also been called the occult stage of DCM. The term occult refers to the
owner’s perspective; that is, from the owner’s point of view, the dog appears
normal despite laboratory evidence of abnormality. The morphologic
abnormality consists of left ventricular (LV) enlargement in systole and/or
diastole. The electrical abnormality consists of the presence of premature
ventricular contractions (PVCs). These abnormalities, morphologic or
electrical, may coexist or may be of predominantly one form at any time
during this occult stage. In Doberman Pinschers, most occult dogs have
evidence of both abnormalities. Stage III is characterized by the presence of
clinical signs of heart failure. We also refer to this stage as the overt stage of
DCM. Because most dogs are nonworking, evidence of exercise intolerance
is usually lacking until the onset of pulmonary edema and congestive heart
failure (CHF). We did observe a fly ball racing Doberman Pinscher that
demonstrated a normal response time 2 weeks before the onset of pul-
monary edema, however. Similar observations have occurred among human
athletes demonstrating normal performance time intervals in the face of
substantive loss of systolic function. DCM is inevitably fatal unless the
etiology can be reversed.

Occult stage of dilated cardiomyopathy

There are few descriptions of the occult stage of DCM. Most of the
available data has been derived from the Doberman Pinscher. In the
Doberman Pinscher, the occult stage lasts 2 to 4 years if evidence of
the occult stage is detected early. The common clinical signs that herald
the onset of the final stage of DCM are evidence of respiratory distress,
syncope, and sudden death. In the Doberman Pinscher, multiple syncopal
events are rare; these dogs usually die with the first collapsing event. Sudden
death is the first clinical sign of DCM in approximately 30% of dogs [10,11].
We presume that sudden death is the result of paroxysms of ventricular
tachycardia that progress to ventricular fibrillation [12]. Presumably in-
frequently, however, bradyarrhythmias may precede the onset of sudden
death in some Doberman Pinschers [5,13].
1190 M.R. O’Grady, M.L. O’Sullivan / Vet Clin Small Anim 34 (2004) 1187–1207

In a small study of the natural history of DCM in Doberman Pinschers,

100% of the dogs that demonstrated at least 1 PVC on a 3-minute
electrocardiogram, 100% of the dogs with an M-mode long-axis echocar-
diographic left ventricular internal dimension (LVID) at end systole of
greater than 38 mm, and 85% of the dogs with an LVID at end diastole of
greater than 46 mm went on to develop clinical DCM [14]. These numbers
were based on a 28-month follow-up of 103 Doberman Pinschers free of
clinical signs, wherein 29 dogs went on to develop clinical signs of DCM
(stage III) and to die. We believe that these criteria for occult DCM may not
be ideal for either small (especially female) or extremely large (especially
male) Doberman Pinschers. Our continued work on the natural history of
DCM in Doberman Pinschers suggests that an LVID at end diastole of
greater than or equal to 49 mm or at end systole of greater than or equal to
42 mm has a high positive predictive value for identifying Doberman
Pinschers with occult DCM independent of the size of the dog [15]. With
respect to the presence of PVCs, we are using the criteria of greater than or
equal to 1 PVC per minute on a resting electrocardiogram as evidence of
occult DCM. Note that we have observed dogs with right-sided PVCs (left
bundle branch block morphology) from time to time. We suspect the finding
of these right-sided PVCs is not indicative of occult DCM, however, because
Doberman Pinschers usually have left-sided PVCs. A 24-hour Holter
examination has been recommended to identify Doberman Pinschers with
occult disease [11,16]. The finding of greater than 50 PVCs in 24 hours has
been suggested as indicative of occult DCM.
The use of echocardiographic fractional shortening (FS) in Doberman
Pinschers free of clinical signs as a discriminating marker for the presence or
absence of DCM is unreliable. Certainly, a FS of less than 15% is strong
evidence of occult DCM; however, we have observed normal Doberman
Pinschers with FS values in the range of 18% to 22% [17]. Note that FS
determined from a right parasternal short-axis view is greater than FS
determined from a long-axis view. Studies conducted at the University of
Guelph involve FS determined from a long-axis view.
In North America, atrial fibrillation is a frequent finding in Irish
Wolfhounds free of clinical signs and frequently does not herald impending
DCM [18]. In a European study, atrial fibrillation was rarely present in the
absence of DCM [19]. In this study of 500 Irish Wolfhounds, 49 were
diagnosed with occult DCM based on echocardiographic criteria. Atrial
fibrillation was detected in 73% of these occult dogs. Atrial fibrillation was
also detected in 11 dogs that did not meet the criteria for occult or overt
DCM. Of these, at least 3 dogs went on to develop occult or overt DCM.
Atrial fibrillation is a common finding in dogs that suddenly present with
clinical signs. We presume that compensated dogs, previously occult,
decompensate with the development of atrial fibrillation.
The identification of predictors of prognosis for dogs in the occult stage
of DCM has important implications for therapeutic interventions and
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decision making. There are few data in this area in the human or veterinary
literature. Sudden death is an important outcome in this stage of DCM.
Predictors of sudden death continue to be a controversy in human and
veterinary cardiology. The presence of sustained (>30 seconds) ventricular
tachycardia on a Holter monitoring study was associated with sudden death
in Doberman Pinschers with occult DCM [12]. In a recent investigation of
prognostic indicators in Doberman Pinschers with occult DCM, decelera-
tion time of the transmitral flow (TMF) early filling wave (DTE) was the
only variable (among a number of clinical, neurohormonal, and diastolic
and systolic echocardiographic parameters) predictive of the onset of CHF
or sudden death [20]. For each unit decrease in DTE, there was a 17%
increase in risk of CHF or sudden death. In a human study, a short DTE
(an index of ventricular compliance) was identified as the most powerful
independent predictor of hospitalization for CHF and all-cause mortality in
asymptomatic LV systolic dysfunction patients, irrespective of TMF pattern
and systolic function indices [21].
Owners of breeds like the Doberman Pinscher and Irish Wolfhound must
be advised that annual screening in the form of an echocardiogram or
a Holter examination is required, because the age of onset of occult DCM is
highly variable.

Overt stage of dilated cardiomyopathy

Unless an underlying cause for DCM can be identified and reversed
(eg, taurine deficiency), the prognosis after the onset of CHF is generally
poor but highly variable. Sudden death as a result of arrhythmias, death
caused by severe pulmonary edema, and euthanasia due to intractable CHF
are the typical modes of cardiovascular death in DCM patients. Depending
on the severity of disease, response to therapy, breed, age, and presence of
atrial fibrillation, to name only a few factors, survival times may range from
only a day to several years after diagnosis. Reported survival data have
arisen from two main sources: retrospective reviews and prospective clinical
trials. Comparing survival data between studies is further complicated
because of the variable therapies used, various breeds studied, and potential
geographic differences in frequency and timing of euthanasia. In addition,
survival is not determined by the date of death in most veterinary studies;
instead, time to adverse outcome is usually used. Adverse outcome is usually
defined as withdrawal from the study because of failure to improve or
getting worse; death caused by heart failure, including sudden death; and
euthanasia due to heart failure.
Unlike occult DCM, there are data concerning the overt stage of DCM in
breeds other than the Doberman Pinscher. In a retrospective analysis,
Monnet et al [22] observed a median survival time of 65 days in a group of
37 dogs of various breeds with DCM, including occult and overt disease.
The probability of survival at 1 year was 37.5%; at 2 years, it was 28%. In
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the largest retrospective study (189 dogs of various breeds with DCM and
CHF), Tidholm et al [23] reported mean and median survival times of 175
and 27 days, respectively, with a range of 0 to 1640 days. The survival rate at
1 year was 17.5% in this study; at 2 years, it was 7.5%. In the Long-Term
Investigation of Veterinary Enalapril (LIVE) trial, the effect of enalapril
versus placebo was examined in 43 dogs with DCM and CHF [24]. Average
time to adverse outcome was 143 days in the enalapril group and 57 days in
the placebo group (P = 0.06). Similarly, in the BENCH trial, the effect of
benazepril versus placebo on time to adverse outcome was examined in 37
dogs with DCM and CHF [25]. Longer ‘‘survival’’ times were found in this
study, with a mean of 394 days in the benazepril group and 164 days in
the placebo group (P = 0.66), potentially reflecting differences in stage of
disease at the time of diagnosis, breed distribution, or euthanasia practices.
We believe sudden death is much higher in Doberman Pinchers than in
other affected breeds [26]. Sudden death occurs in about 30% to 50% of
Doberman Pinschers in this stage. We have the impression that female dogs
may be slightly more prone to develop sudden death than male dogs;
however, this remains to be confirmed. In Newfoundlands, sudden death
occurred in 8% of a pool of 37 dogs with CHF as a result of DCM [27]. In
a mixed group of 189 dogs with DCM and CHF, 10% demonstrated sudden
death [23]. Clearly, sudden death is more likely to be observed if dogs are not
euthanized. As is the case with dogs with occult DCM, we believe sudden
death results from the development of paroxysms of ventricular tachycardia
that progress to ventricular fibrillation. The prevalence of ventricular ectopy
has been reported as 92% in Doberman Pinschers [28], 16% in Newfound-
lands [27], and 21% in a pool of various breeds with DCM [29].
In human idiopathic DCM, approximately 25% of newly diagnosed
symptomatic patients die within 1 year and 50% die within 5 years [3].
Given the potential for some patients to improve, whereas others with poor
short-term outcomes require cardiac transplantation, the identification of
predictors of prognosis is critical for therapeutic monitoring and decision
making. Furthermore, predictors of prognosis are often used as a stratifica-
tion tool in the design of clinical trials. Prognostic indicators in human
DCM have included New York Heart Association (NYHA) functional
class; hemodynamic variables, including pulmonary capillary wedge pres-
sure, LV end-diastolic pressure, and pulmonary artery pressures; and
electrocardiographic findings of frequent and complex ventricular arrhyth-
mias or atrial fibrillation [30–33]. Markers of neuroendocrine activation,
including low plasma sodium and increased plasma norepinephrine, atrial
natriuretic peptide (ANP), brain natriuretic peptide (BNP), and big
endothelin-1 (ET-1), are strong independent predictors of poor prognosis
[34–39]. Certain echocardiographic indices, such as simple measures of size
(LV dimensions indexed to body size) and systolic function (ejection
fraction) have variably been predictive of outcome [30–32,40,41], whereas
others have been more definitively linked with a poor prognosis, such as
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evidence of right ventricular (RV) dilation and tricuspid regurgitation

(indicative of RV dysfunction) [3,42]; increasing grade of mitral and tricuspid
regurgitation [43]; and evidence of advanced diastolic dysfunction, including
a TMF pattern (typically, E/A ratio
2 and/or short DTE) and blunted
systolic pulmonary venous flow (peak velocity and duration) [21,44–46].
Few studies have been described in dogs with the purpose of determining
prognostic indicators for DCM, and predicting prognosis in any given single
patient continues to be a challenge. In the retrospective analysis of 37
symptomatic and asymptomatic dogs with DCM, of the 27 variables
assessed using bivariate Cox proportional hazard analysis, only pleural
effusion and pulmonary edema present radiographically were significant
predictors of poor prognosis [22]. Having examined a small group of dogs
with and without clinical signs, these findings mirror the timeline described
in Fig. 1. In a larger study, Tidholm et al [23] concluded that of 27 variables
examined, 3 were independent predictors of survival: age (with young age at
onset of clinical signs being an indicator of poor prognosis), dyspnea, and
ascites (the latter two as identified on physical examination). The presence of
dyspnea and ascites suggests more advanced CHF. This finding agrees with
human studies demonstrating the effect of NYHA class score on outcome.
In Doberman Pinschers, the presence of bilateral CHF predicted a poorer
prognosis [47]. Vollmar [19] demonstrated that Irish Wolfhounds with more
advanced clinical signs had a worse outcome.
Atrial fibrillation is associated with an adverse outcome in people with
CHF [48]. The impact of atrial fibrillation has been assessed in Doberman
Pinschers [47]. In this study, the overall survival for Doberman Pinschers
with CHF was 6.5 weeks (median); with only left-sided CHF without atrial
fibrillation, it was 7.5 weeks; with bilateral CHF without atrial fibrillation, it
was 2.8 weeks; with atrial fibrillation, it was 2.9 weeks; and with bilateral
CHF and atrial fibrillation, it was 2.0 weeks. Tidholm et al [23] observed
that atrial fibrillation was not associated with increased mortality. They
noted, however, that the rate of euthanasia may be higher in Sweden than in
North America. Approximately 30% of Doberman Pinschers develop atrial
fibrillation [47]. Tidholm et al [23] demonstrated a 46% prevalence of atrial
fibrillation in 142 dogs with DCM, most of which were not Doberman
Pinschers. Liu and Tilley [49] state that atrial fibrillation occurs in 75% to
80% of giant-breed dogs with DCM. Vollmar [19] observed atrial
fibrillation in 97% of Irish Wolfhounds with DCM. A comparison of the
impact of atrial fibrillation in Doberman Pinschers versus other breeds has
yet to be reported.
Age has been reported to affect outcome such that younger dogs had
a worse outcome [23]. In a recent investigation of prognostic indicators in
Doberman Pinschers with DCM and CHF, age was likewise predictive of
survival time [20]. Calvert [50] suggested that younger Doberman Pinschers
(\2 years of age) have a worse outcome, and Vollmar [19] suggested that
young Irish Wolfhounds (\1.5 years of age) have a worse prognosis.
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Some investigators have found certain echocardiographic measures to be

predictors of prognosis, including end-systolic volume index, a restrictive
TMF pattern, and a short (\80 milliseconds) DTE, whereas FS, E-point–to-
septal separation, and left atrium/aortic root ratio were not of use [51]. In
Doberman Pinschers with DCM and CHF, LVID in diastole and LVID in
systole were predictive of survival time [20]. Monnet et al [22], however,
found that echocardiographic measures of LV size indexed to body size and
measures of systolic function were not predictors of survival. We also
examined a number of clinical, echocardiographic (including systolic and
diastolic indices), and neurohormonal indices [20]. None of the diastolic
indices or neurohormones at enrollment was a significant univariate
predictor of survival. In contrast, absolute and percent change in norepi-
nephrine and big ET-1 from enrollment to the 1-month recheck were
significant predictors of survival [20].
Thus, a number of variables may provide important prognostic in-
formation; however, the predictive reliability of any single variable on its
own is likely poor, and assessment of prognosis of an individual patient on
one initial screening examination continues to be difficult.

Prevalence
DCM is considerably less common than chronic mitral valve disease.
DCM is typically observed in large- and giant-breed dogs; however, it has
been recognized in medium-sized dogs, such as English and American
Cocker Spaniels and Dalmatians. On rare occasions, we have observed
DCM in small-breed dogs such as the West Highland White Terrier.
The prevalence of DCM is difficult to ascertain. In an Italian study
reported in 1988, 1.1% of 7148 dogs were diagnosed with DCM [52]. A
review of the findings of the Veterinary Medical Database of Purdue
University revealed a diagnosis of DCM (acquired, congestive, or right-
sided cardiomyopathy) in 0.5% of canine referrals [26]. A review of the
University of California Veterinary Database of cases referred between 1986
and 1996 revealed that 0.35% of cases were identified as DCM [5]. Note that
these data reflect the bias of a referral population. Thus, the ‘‘true’’
prevalence of DCM should be somewhat less. Note also that sudden death
is a common first clinical sign of DCM; unless owners of dogs with sudden
death seek a postmortem examination, DCM will likely go unrecognized
[10,11]. Such cases cause the prevalence of DCM to be underrepresented.
The University of Purdue Veterinary Medical Database identified breeds
commonly affected with DCM (Table 1) [26]. Other breeds known to be
affected with DCM or that we have observed with DCM that are not
represented in the Purdue database are German Shepherds, Salukis, Bull
Mastiffs, Bouvier des Flandres, Irish Setters, Bearded Collies, Bloodhounds,
Dogue de Bordeaux, Standard Poodles, Siberian Huskies, Staffordshire
 M.R. O’Grady, M.L. O’Sullivan / Vet Clin Small Anim 34 (2004) 1187–1207 1195

Table 1
Breeds predisposed to dilated cardiomyopathy
No. with % with % of DCM
Breed DCM Total referrals DCM by breed
Scottish Deerhound 7 117 6.0 0.5
Doberman Pinscher 603 10,435 5.8 45.9
Irish Wolfhound 38 696 5.5 2.9
Great Dane 122 3157 3.9 9.3
Boxer 131 3800 3.4 10.0
Saint Bernard 29 1124 2.6 2.2
Afghan Hound 15 897 1.7 1.1
Newfoundland 22 1751 1.3 1.7
English Sheepdog 18 1894 1.0 1.4
English Cocker Spaniel 5 729 0.7 0.4
Springer Spaniel 25 4865 0.5 1.9
American Cocker Spaniel 53 15,373 0.3 4.0
Labrador Retriever 73 21,501 0.3 5.6
Golden Retriever 42 16,405 0.3 3.2
Mixed breeds 131 83,417 0.2 10.0
Abbreviation: DCM, dilated cardiomyopathy.
Data from the University of Purdue Veterinary Medical Database 1985 to 1991 [26].

Terriers, and Dalmatians. A recent Swedish study noted that Airedale

Terriers, English Cocker Spaniels, and Standard Poodles were at increased
risk for DCM as well as many of the breeds commonly observed in North
America (Boxers, Doberman Pinschers, Newfoundlands, and Saint Ber-
nards) [29]. This study also noted that Great Danes, Old English Sheepdogs,
and Irish Wolfhounds were not at an increased risk of acquiring DCM. In
another European study, 24% of 500 Irish Wolfhounds were diagnosed with
DCM [19]. These differences may reflect a genetic difference in some breeds
between regions.
There is a gender bias in dogs with DCM. The early descriptions of DCM
suggested that this was a disorder of primarily the male gender. More recent
work continues to demonstrate that male dogs are more frequently affected
than female dogs but that the disorder is much more prevalent in female
dogs than previously suspected. In Doberman Pinschers, approximately
50% of male dogs and 33% of female dogs develop DCM [10]. In the
University of Purdue Veterinary Medical Database, only the Springer
Spaniel had more female dogs diagnosed with DCM than male dogs [26].
One study in Sweden observed no sex predilection in Newfoundlands [27].
It is reported that female Doberman Pinschers manifest overt DCM at
a slightly older age than male Doberman Pinschers, with a median age for
female dogs of 9.5 years and a median age for male dogs of 7.5 years [47].
Doberman Pinschers can manifest clinical DCM over a wide age range,
however, from 2 to 15 years of age. Our work suggests that approximately
25% of Doberman Pinschers older than 10 years of age manifest clinical
DCM. Thus, breeders can virtually never be assured that a dog is free of
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developing DCM. In other breeds, the mean ages of onset of clinical signs
are 6.6 years in a mixed pool of dogs in Sweden [23], 4.2 years in Irish
Wolfhounds [19], and 8 years in a mixed pool of dogs in Europe [25].

Diagnosis
The reader is referred to excellent reviews of the diagnosis of canine
DCM [4–6,11,26,53–55]. In terms of newer modalities for the diagnosis of
DCM, preliminary investigations suggest several technologies that may
prove useful in the future, potentially allowing earlier detection of disease,
and hence earlier intervention, as well as confirmation of equivocal results
from other routine diagnostic tests. Circulating markers of LV systolic
dysfunction, including BNP and cardiac troponins (cTn-I), may be useful in
this regard, potentially identifying dogs in the occult stage, even before
electrically or morphologically detectable abnormalities occur [56–58].
Novel echocardiographic modalities, such as tissue Doppler imaging
(TDI), may identify occult disease earlier than with traditional echocardio-
graphic parameters. Mitral annular systolic motion has been proposed as
a sensitive measure of systolic function in human DCM patients because it is
less load dependent and much more sensitive to changes in contractility than
traditional echocardiographic indices [59]. TDI, specifically systolic myo-
cardial velocity gradient (MVG), was able to detect early myocardial
dysfunction despite normal LV dimensions and shortening in puppies with
the X-linked mutation of the dystrophin gene responsible for Golden
Retriever muscular dystrophy [60]. Other investigators are examining the
utility of TDI MVG and myocardial strain rate in the identification of occult
DCM in Doberman Pinschers [61].
In a group of 10 Doberman Pinschers with occult DCM, select
echocardiographic parameters of diastolic function, namely DTE, systolic
pulmonary venous flow, and velocity of flow propagation by color M-mode,
were significantly different compared with the same parameters in a group of
normal Doberman Pinschers. Likewise, peak systolic mitral annular velocity
by TDI (Sm) was decreased and plasma ANP was increased compared with
the normal group [62]. These indices may therefore have use in the diagnosis
of occult DCM.
Stress echocardiography is a valuable tool in human beings to identify
patients with asymptomatic myocardial dysfunction [63]. Dobutamine stress
echocardiography was assessed in Doberman Pinschers free of clinical signs
[64]. Only an elevated LVID at end systole and reduced TMF E/A ratio
were independent predictors of occult DCM. Similarly, measures of heart
rate variability (HRV) can identify the autonomic nervous system imbalance
that characterizes heart disease [65]. HRV was assessed in this group of
Doberman Pinschers [66]. Time domain and frequency domain parameters
failed to identify dogs with occult DCM.
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Management
The management of DCM is addressed with respect to the stage of heart
failure on presentation. There are a number of excellent reviews of the
management of DCM [4,5,53–55,67] to which interested readers are directed
for discussion of the management of acute CHF and the use of diuretics and
digoxin in chronic CHF.

Management of occult dilated cardiomyopathy

Management of the occult stage of DCM is clearly of value, because this
stage of DCM inevitably progresses to the overt stage and death.
Management of the occult stage involves identifying the cause of DCM,
identifying factors that can precipitate the acute progression to CHF, and
instituting nonspecific measures to delay the progression of DCM from the
occult stage to the overt stage. The most common precipitating factor
involves the development of ventricular and/or supraventricular arrhyth-
mias. Because sudden death is common, especially in the Doberman
Pinscher, and the presence and complexity of PVCs suggest that these
individuals are at risk for sudden death, efforts to reduce the risk of sudden
death are indicated [10,11,16]. At present, no studies have been conducted to
address the potential to reduce the risk of sudden death in this cohort of
dogs. Even though antiarrhythmic agents are used to reduce the risk of
sudden death, the human experience in such cases suggests that most
antiarrhythmic agents are ineffective in this capacity. In fact, most
antiarrhythmic agents probably increase the risk of sudden death in people.
The most promising of the antiarrhythmic agents are amiodarone and
sotalol. Amiodarone is a drug with substantive clinical concerns, however,
including potentially severe toxicity and unusual pharmacokinetics and
pharmacodynamics, which make appropriate dosing uncertain at this time.
Although sotalol seems to be less problematic, convincing evidence of its
efficacy is lacking in the human arena and no work has been undertaken in
canine DCM. Although there is some evidence for the efficacy of mexiletine
plus atenolol or sotalol in the management of PVCs in Boxers [68], no
controlled studies have been conducted with DCM.
Only angiotensin-converting enzyme (ACE) inhibitors have been in-
vestigated in the setting of occult DCM [15]. This retrospective study defined
the presence of occult DCM as having an LVID at end diastole of greater
than or equal to 49 mm or of greater than or equal to 42 mm at end systole.
The absence, presence, or severity of ventricular arrhythmias at the time of
enrollment was not considered. Sixty-one Doberman Pinschers with occult
DCM were identified, with 34 having received ACE inhibitor therapy and 27
having received no therapy during the occult stage. There was a significant
delay in the time to onset of the overt stage of DCM with the use of ACE
inhibitors (601 days) versus no therapy (314 days).
1198 M.R. O’Grady, M.L. O’Sullivan / Vet Clin Small Anim 34 (2004) 1187–1207

The role of beta-blockers or aldosterone blockade remains to be

determined. In consideration of the role of the sympathetic nervous system
and the renin-angiotensin-aldosterone system (RAAS) in the development
and progression of heart failure, it may well be that these therapeutic efforts
are of merit. At present, although some studies are underway, there are no
reports evaluating the efficacy of these agents in the occult setting of DCM.

Management of overt dilated cardiomyopathy

Angiotensin-converting enzyme inhibitors
Two ACE inhibitors have been studied in canine DCM. The merit of
therapy must be considered with respect to quality of life and survival.
Enalapril was first evaluated in this context. Three studies were undertaken
to assess the utility of enalapril when used in conjunction with diuretics with
or without digoxin [24,69,70]. With respect to quality of life, there are
compelling data to suggest that enalapril improves quality of life when
compared with placebo [69,70]. With respect to survival, the reports of the
LIVE study promote confusion. The initial report indicated a significant
benefit in favor of enalapril compared with placebo [71,72]. The time to
adverse outcome was significantly longer for enalapril (158 days) versus
placebo (58 days). Adverse outcome was defined as died of heart failure,
died suddenly, or demonstrated inadequate improvement. The follow-up
publication provided rather different results [24]. Forty-three dogs were
studied: 21 dogs were allocated to the placebo treatment and 22 received
enalapril. The time to adverse outcome trended to significance (P = 0.06),
with a longer time for enalapril (143 days) versus placebo (57 days). It seems
that the earlier report involved a number of dogs that were subsequently
excluded from the final publication. Several important issues are worthy of
note. First, the number of dogs enrolled was small when compared with
human studies that frequently enroll thousands of subjects, limiting the
ability to find a significant difference. Excluded from the study were dogs
believed to have a life expectancy of less than 1 month. In clinical practice, it
is often difficult to predict which dogs will succumb in less than 1 month.
As clinicians, we endeavor to treat dogs with a poor life expectancy as well
as those with a better outcome. Thus, it is difficult to extrapolate from this
study as to the ‘‘real’’ impact of enalapril on all cases of CHF caused by
DCM.
The second ACE inhibitor investigated was benazepril in the BENCH
trial [25]. Thirty-seven dogs with CHF caused by DCM were enrolled: 17
dogs received benazepril and 20 received placebo. With respect to quality of
life, there was significant improvement in the pool of dogs with CMVI and
DCM. Data exclusive to the DCM pool are not provided in the report.
Because dogs with DCM constituted only 23% of the pool, we are unable to
infer benefit. The time to adverse outcome in the dogs with DCM was not
significantly different (P = 0.66), with a longer time for benazepril (394
 M.R. O’Grady, M.L. O’Sullivan / Vet Clin Small Anim 34 (2004) 1187–1207 1199

days) versus placebo (164 days). In addition, the authors evaluated time to
worsening heart failure for dogs with mild to moderate heart failure at the
time of enrollment. Twelve dogs administered benazepril and 10 dogs
administered placebo were analyzed. The mean time for the dogs admin-
istered benazepril was 341 days, and for the dogs administered placebo, it
was 51 days (P = 0.95). Unlike the enalapril trial, there was no exclusion of
dogs with a projected short life expectancy. When comparing the LIVE and
BENCH trials, it is interesting that survival in the benazepril study is longer
than in the enalapril study even though the benazepril study presumably
included some dogs with a shorter life expectancy. As with the previous
study, the number of dogs enrolled in the BENCH trial is small, which
makes finding a significant difference unlikely. Finally, 16 dogs, 10
administered benazepril and 6 administered placebo (the report does not
specify whether these were dogs with DCM or CMVI), received no diuretics.
This suggests that these dogs were not in CHF at the time of enrollment, and
the inclusion of these dogs in the study complicates the answer to the
question, ‘‘What is the effect of benazepril on survival and clinical signs of
dogs with CHF?’’
In conclusion, ACE inhibitors improve the quality of life for dogs with
CHF caused by DCM. As for survival, there is a plethora of evidence in
people with CHF caused by DCM indicating the significant role these agents
play in reducing mortality [3]. It is our belief that ACE inhibitors would
have demonstrated a significant improvement in survival had greater
numbers of dogs been enrolled. Therefore, we continue to recommend the
use of ACE inhibitors for this stage of DCM.

Pimobendan
A detailed discussion of the use of pimobendan is found elsewhere in this
issue. Pimobendan is a new positive inotrope and vasodilator that has been
available in Europe for several years to treat CHF caused by DCM in the
dog. Pimobendan is a benzimidazole pyridazinone derivative. It mediates its
positive inotropic properties by two mechanisms. First, it belongs to a new
class of positive inotropes called calcium sensitizers. These agents induce an
increase in contractility by increasing the sensitivity of the regulatory
protein, troponin C, to the existing Caþþ in the cell. All other positive
inotropes induce an increase in contractility by increasing Caþþ entry into
the cell and have failed to increase survival in people with systolic
dysfunction as the cause of CHF. They mediate their deleterious long-term
response, in large part, by adversely affecting the balance of myocardial
oxygen consumption and supply. The calcium sensitizers may, however,
represent a new means of augmenting contractility without adversely
affecting this balance. In fact, myocardial oxygen kinetics seem to be
improved with pimobendan [73,74]. The second method whereby pimoben-
dan increases contractility is via phosphodiesterase III inhibition. This
method of increasing contractility is identical to that of milrinone and
1200 M.R. O’Grady, M.L. O’Sullivan / Vet Clin Small Anim 34 (2004) 1187–1207

amrinone. The vasodilation property of pimobendan is a result of the

peripheral action of phosphodiesterase III and V inhibition. This results in
venous and arterial vasodilation.
Several studies have evaluated the efficacy of pimobendan in dogs with
CHF caused by DCM. The first involved two populations of dogs:
Doberman Pinschers and English Cocker Spaniels [75]. It is noteworthy
that the authors did not mix these dogs but studied the effect of pimobendan
on the two populations independently. All dogs enrolled received concurrent
furosemide, enalapril, and digoxin. The dogs were randomized by breed to
receive pimobendan (5 dogs) or placebo (5 dogs). Quality of life was
improved in both pimobendan groups compared with the placebo group.
For the Doberman Pinscher group, the median survival was significantly
improved with pimobendan (329 days) versus placebo (50 days). Analysis of
the baseline criteria revealed that 3 of the dogs administered placebo and
only 1 of the dogs administered pimobendan had atrial fibrillation at
enrollment. Because atrial fibrillation has a marked adverse impact on
outcome [47], the two treatment groups were severely imbalanced at
enrollment in favor of pimobendan. Nevertheless, the length of survival
observed in the dogs administered pimobendan markedly surpassed that
observed in Doberman Pinschers with CHF in North America, whereas the
length of survival observed in Doberman Pinschers administered placebo
was similar to that observed in North America. The Cocker Spaniel group
was followed for 4 years; at the end of this time, 9 of 10 dogs had not met the
primary end point criteria (6 were still alive, and 3 had died of noncardiac
disease). Thus, the impact of pimobendan on survival could not be assessed
in this group.
The next study that assessed the role of pimobendan in the management
of CHF involved a pooled canine population with DCM and CMVI [76].
The authors did not evaluate the effect in DCM independent of CMVI.
Eighty-one dogs with DCM, 23 dogs with CMVI, and 1 dog with tricuspid
valve insufficiency were enrolled. The study had a two-phase design
involving a 4-week quality-of-life assessment and a subsequent optional
survival phase. Three treatment groups were studied: one randomized to
pimobendan alone, another to benazepril alone, and the third to the
combination of pimobendan and benazepril. All dogs received concurrent
furosemide. There was improved quality of life with benazepril and
pimobendan and pimobendan alone compared with benazepril alone. In
the long-term survival study, 73 dogs were assigned to pimobendan and 37
were assigned to placebo. Time to adverse outcome was assessed similar to
that described for the ACE inhibitor trials. The median time to adverse
outcome was significantly better with pimobendan (217 days) versus placebo
(42 days). Because the DCM population comprised 77% of the pool of dogs,
one would expect that the observed benefit was primarily a result of the
influence of pimobendan on the dogs with DCM. This remains to be
demonstrated, however.
 M.R. O’Grady, M.L. O’Sullivan / Vet Clin Small Anim 34 (2004) 1187–1207 1201

The final report studied Doberman Pinschers with CHF caused by DCM
[77]. This was a single-blind (only the owners were blinded to the treatment
limb) randomized study comparing the efficacy of pimobendan versus
placebo in dogs receiving furosemide and benazepril. An interim report
involved seven dogs administered pimobendan and eight dogs administered
placebo. Dogs with atrial fibrillation at enrollment were excluded. The end
points were time to treatment failure and survival. Treatment failure was
defined as a failure of furosemide, 5 mg/kg administered orally every 8
hours, to resolve respiratory distress. If sudden death, death caused by heart
failure, or euthanasia as a result of heart failure occurred before achieving
this dose of furosemide, the death date was used as the treatment failure
date. Once the dogs reached treatment failure as a result of inadequate
diuresis, they were offered pimobendan; however, the owners continued to
remain blinded. An intention-to-treat analysis was performed. There was
significant improvement in quality-of-life indices at 1 and 2 months with
pimobendan. There was a significant improvement in time to treatment
failure with pimobendan (126 days) versus placebo (26 days) and in survival
with pimobendan (128 days) versus placebo (63 days). Together, these data
provide strong evidence of the ability of pimobendan to improve quality of
life and survival in dogs with DCM and CHF. This benefit was observed in
the face of ACE inhibition. Expect to see more studies assessing the role of
pimobendan in dogs with CHF in the near future.

Beta-blockers
There is a plethora of evidence in people with CHF caused by DCM
demonstrating the efficacy of beta-blockers when used with a background of
ACE inhibition [3]. Beta-blocker therapy counters the maladaptive neuro-
hormonal response that occurs when cardiac output is reduced. No clinical
trials have been reported in dogs evaluating the efficacy of beta-blocker
therapy in cases of CHF. Some general comments concerning beta-blocker
therapy are worthwhile. Because these are negative inotropes, dogs can
decompensate as beta-blocker therapy is initiated. The rule of thumb in
people is to start at a low dose and slowly increase the dose to the
maintenance level. The appropriate starting dose, rate of increase, and
maintenance dose have all yet to be determined for beta-blocker therapy.
Beta-blockers should be started once respiratory distress has been alleviated.
A number of investigators are beginning to collect data on the use of beta-
blockers in the veterinary cardiac patient [78]. Guidelines to their use should
be available in the near future.

Spironolactone
The recent study in people demonstrating the efficacy of spironolactone
in the management of CHF has stimulated an interest in the use of
spironolactone in dogs with CHF caused by DCM [79]. To date, no studies
have assessed the role of spironolactone in canine CHF. Because the RAAS,
1202 M.R. O’Grady, M.L. O’Sullivan / Vet Clin Small Anim 34 (2004) 1187–1207

in general, and aldosterone, in particular, are elevated in dogs with CHF

caused by DCM, it is reasonable to expect that aldosterone blockade will be
as useful in the management of CHF caused by DCM as it is for people
similarly affected.
Antiarrhythmic therapy
PVCs are a common part of the clinical presentation of DCM in dogs,
particularly in the Doberman Pinscher [27–29]. It is probable that either the
frequency of PVCs or the complexity of premature beats identifies dogs at
risk for sudden death or reduced survival. If this is the case, intervening with
antiarrhythmic agents might be worthwhile. There have been no studies
conducted in the dog to address the efficacy of antiarrhythmic therapy in
this setting. The experience in people suggests that class I antiarrhythmic
agents are ineffective at preventing sudden death in patients with DCM and
are likely to promote arrhythmic sudden death. Of all antiarrhythmic
agents, only the class III agents are likely to be useful to prevent sudden
death in people. Although we have used class III agents in dogs with DCM,
with the absence of veterinary data in a controlled setting, we do not know if
these agents prevent sudden death. We recommend a therapeutic plan that
focuses on controlling pulmonary edema, use of ACE inhibitors at optimal
doses, use of pimobendan if available, and optimizing electrolyte balance to
hopefully reduce the frequency of ventricular ectopy and sudden death.

Other therapies
A great number of other therapies have been recommended. These include
a low-sodium diet; exercise restriction; and supplementation of taurine,
carnitine, fish oil, magnesium, coenzyme Q 10, and vitamin E. Interested
readers are referred elsewhere to address these issues [2,4,5,26,53,54,67,80].
We wish to address the issue of resynchronization therapy briefly. In short,
substantial evidence exists for the favorable effect of resynchronization
therapy in the management of people with CHF caused by systolic
dysfunction [81]. Gordon [82] undertook a preliminary investigation of the
role of resynchronization therapy in a sample of Doberman Pinschers with
CHF caused by DCM. This study demonstrated that VDD pacing from the
left ventricle, right ventricle, or both ventricles simultaneously was feasible.
The preliminary evidence suggested that resynchronization therapy is
ineffective in Doberman Pinschers with DCM, however. Furthermore, these
dogs seemed to have features similar to those of the cohort of people who fail
to respond, including global myocardial disease and the absence of
significant intraventricular conduction delay.

Summary
Despite many advances in the diagnosis and treatment of DCM, it
continues to be an important cause of cardiovascular morbidity and
 M.R. O’Grady, M.L. O’Sullivan / Vet Clin Small Anim 34 (2004) 1187–1207 1203

mortality in large-breed dogs. In the coming years, it is hoped and

anticipated that further discoveries will be made in the areas of etiology,
therapy, and assessment of prognosis, ultimately with a view to having
a greater impact on the clinical management of these cases.

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