Managing dilated cardiomyopathy (Proceedings)

Etiology

The cause(s) of dilated cardiomyopathy (DCM) in dogs is (are) unknown. Some of the proposed causes of DCM include: genetic defect(s), viral infection, microvascular spasm, chemical toxin(s), dietary deficiency, and immune-mediated processes. There appears to be a familial predisposition to the development of DCM in some breeds of dogs, and many investigators suspect a heritable defect in the metabolic processes of myocardial cells. It is quite possible that DCM is not a single disease, and that there are many etiologies. Taurine deficiency has been convincingly shown to be a reversible cause of DCM in cats and is also a suspected cause of DCM in foxes, but is not an important cause of DCM in dogs-except in Cocker spaniels. A number of chemical toxins (anthracycline antibiotics, gossypol, monensin) have been shown to cause myocardial failure. There is evidence that Adriamycin exerts at least some of its toxic myocardial effects by inducing histamine and catecholamine-mediated microvascular spasm.

One of the most frustrating aspects of attempts to identify the etiology behind DCM is determining if changes in protein expression are primary or secondary in nature. Up-regulation and down-regulation of proteins responsible for cardiac contraction ( 1, 2, and a receptors), ventricular relaxation (SERCA2, phospholamban) and energy production (carnitine transport, creatine kinase) occur to equivalent degrees in volume overload, pressure overload, and cardiomyopathy. "In this respect the intracellular biochemical specificity of the response of the myocyte to a chronic insult appears to be relatively restricted. The foremost question remains, which, if any, are the true pathogenic alterations and which are cellular adaptations."

Epidemiology

The exact prevalence of DCM is unknown, but it is believed to be the most common cause of cardiac disability in large and giant breed dogs. Although DCM has been identified with increasing frequency in medium size breeds such as English and American cocker spaniels, this disease remains primarily a disease of large and giant purebred dogs. According to the Purdue VMDB the prevalence rate of DCM was highest in Scottish deerhounds (6.0 percent), Doberman pinschers (5.8 percent), Irish wolfhounds (5.6 percent), Great Danes (3.9 percent), Boxer dogs (3.4 percent), Saint Bernards (2.6 percent), Afghan hounds (1.7 percent), Newfoundlands (1.3 percent), and Old English sheepdogs (0.9 percent). The prevalence of DCM was 0.69 percent in English cocker spaniels and 0.34 percent in American cocker spaniels. Dogs of both sexes and all ages may be affected but the disease is most commonly diagnosed in middle-aged male dogs. The prevalence of DCM increases with age (VMDB). However, because of the lower number of aged dogs examined, the majority of dogs presented for evaluation and treatment of DCM and heart failure are between 4 and 10 years old. The prevalence of DCM in male dogs (0.66 percent) is nearly twice that of female dogs (0.34 percent) according to the VMDB. An autosomal dominant mode of transmission has been reported in the Irish Wolfhound, Newfoundlands, and Doberman Pinschers. In the juvenile Portuguese Water Dog, an autosomal recessive transmission has been documented.

History and clinical signs

Affected dogs are usually presented with rapidly progressing clinical signs that the owner has been aware of for only a few weeks. Weakness and exercise intolerance are often the first signs noticed by the owner. The spectrum of clinical signs exhibited by dogs with DCM is similar in all breeds, but the observed frequency of these signs differs between the various breeds and, to some extent, with the lifestyle of the animal. Right sided heart failure manifested as abdominal distension, anorexia, weight loss, and fatigue often predominates in giant breeds, while signs of left heart failure or syncope are more common in Doberman pinschers and Boxer dogs. More variable signs include anorexia, weight loss, syncope and sudden death. These latter two events appear to be most common in Boxer dogs and Doberman pinschers.

Physical examination

Physical examination almost always reveals the presence of a protodiastolic gallop. A ventricular gallop, S3 heart sound, is an important finding and is most easily appreciated in those dogs in sinus rhythm. Soft regurgitant systolic murmurs, typically grades II-III/VI, are frequently heard over the left or right AV valve regions (due to dilatation of the AV annulus). These findings are eclipsed in many dogs by pronounced irregularity of the heart sounds ("delirium cordis"), caused by atrial fibrillation. A variety of other ventricular and supraventricular arrhythmias may be present, underscoring the importance of EGG evaluation of all affected dogs. Weight loss and muscle wasting are common, but variable findings. Ascites, hepatomegaly, venous distention, and jugular pulses are present in dogs with right-sided heart failure. Heart and lung sounds may be muffled as a result of pleural effusion. Rales, crackles, and increased lung sounds may be auscultated in dogs with left heart failure and pulmonary edema. The arterial pulses are typically weak and often irregular with a pulse deficit.

Electrocardiographic associations

Most dogs with DCM have an abnormal electrocardiogram, although the changes may be subtle. High amplitude or widened QRS complexes, indicating left ventricular enlargement, and widened P waves, indicating left atrial enlargement, are commonly observed in dogs with overt heart failure. Of greater clinical importance is the high prevalence of cardiac rhythm disturbances in dogs with DCM. Atrial fibrillation is a common rhythm disturbance reported to be present in as many as 75-80 percent of some giant breed dogs (Great Danes, Irish Wolfhounds, Mastiffs) with DCM. Other common rhythm disturbances include ventricular premature complexes (VPCs) and ventricular tachycardia. Ventricular rhythm disturbances are most common in Boxer dogs and Doberman pinschers, both of which suffer a high rate of sudden death associated with the development of DCM. As many as 80 percent of Dobermans with congestive heart failure manifest ventricular arrhythmias, especially VPCs, on resting electrocardiograms. Using 24-hour ambulatory EGG (Holter) recordings, 81 percent of asymptomatic Doberman Pinschers with DCM had complex ventricular arrhythmias and almost 30 percent had sustained or non-sustained ventricular tachycardia. The prevalence of ventricular tachycardia and VPCs in Boxer dogs is similar to or greater than that observed in Dobermans. Doberman Pinschers and Boxers are reported to present with atrial fibrillation less frequently than other breeds.

Thoracic radiography

Radiographic changes almost always include biventricular or left ventricular and left atrial enlargement as well as evidence of right or left sided heart failure. The degree of cardiomegaly is often less pronounced in Doberman Pinschers and Boxer dogs, even when signs of severe congestive heart failure are present. Pleural effusion is common in dogs with biventricular failure, obscuring thoracic detail and preventing critical evaluation of heart size. Pulmonary edema is present in many dogs with DCM, and is often particularly severe in Boxers and Doberman Pinschers.

Echocardiography

End-systolic and end-diastolic dimensions of the left ventricle are larger than normal. The interventricular septum and ventricular free walls are hypokinetic, often thinner than normal in diastole, and they fail to thicken normally in systole. The papillary muscles often appear flattened and atrophied. The left atrial dimension is increased, and the left atrial to aortic dimension ratio is increased. The ejection phase indices are reduced in magnitude, reflecting the presence of decreased myocardial contractility. Fractional shortening, the percent change in short-axis diameter of the contracting left ventricle, is usually markedly decreased. The distance between the interventricular septum and the mitral valve at its maximal opening point in early diastole (EPSS) is increased as a reflection of a reduced ejection fraction. Aortic excursions have reduced amplitudes. In human patients with left heart failure due to cardiomyopathy, patient survival has been shown to correlate with the ejection phase indices and the size of the left ventricle at end-systole and at end-diastole. Myocardial function is likely to become worse and the longevity of the patient is likely to be shorter as the heart becomes progressively enlarged. In humans with heart failure due to dilated cardiomyopathy, the ratio of left ventricular diastolic diameter to diastolic wall thickness appears to provide one of the best echocardiographic measures of the severity of disease.

Breed-specific idiosyncrasies

Most dogs with dilated cardiomyopathy (classic cardiomyopathy) present with signs of right, left, or biventricular failure, in atrial fibrillation, and with marked weight loss and muscle wasting. In affected Boxers, approximately 1/3 are presented in predominately left-sided failure, 1/3 are presented for syncope or collapse secondary to a rhythm disturbance, and 1/3 are asymptomatic but have rhythm disturbances (primarily ventricular arrhythmias). Atrial fibrillation occurs less frequently in Boxers than in other breeds, and cardiomegaly is usually less marked upon radiographic evaluation. Doberman pinschers usually present in severe left-sided heart failure, have a slightly lower incidence of atrial fibrillation than other breeds, have a higher incidence of ventricular arrhythmia, and experience a higher incidence of syncope and collapse. American and English Cocker spaniels tend to develop generalized cardiomegaly with biventricular failure. They are reportedly more responsive to medical treatment than other breeds. In cases of taurine deficiency some American cocker spaniels respond dramatically to taurine supplementation (+/- carnitine) to the extent that standard medications can be gradually reduced or withdrawn.

Diagnosis

Dilated cardiomyopathy is a diagnosis arrived at by a process of exclusion. Causes such as infectious myocarditis, chronic volume overload (A-V fistula, valvular insufficiency), heartworm disease (and other causes of cor pulmonale), pericardial disorders, and toxic cardiomyopathy (doxorubicin) must be ruled out before a diagnosis of dilated cardiomyopathy is offered. A provisional diagnosis can be based on the history, physical findings, and typical radiographic and electrocardiographic changes, but echocardiographic evaluation is necessary to establish the diagnosis with certainty. Plasma or whole blood taurine concentrations should be obtained when dogs present with evidence of DCM.

Therapy

Medical management of congestive heart failure in dogs with dilated cardiomyopathy includes the use of diuretics to control congestion, angiotensin converting enzyme inhibitors to blunt activation of the renin angiotensin system, and positive inotropes (digoxin or pimobendan) to increase systolic performance. Pimobendan may have the additional benefit of reducing afterload and internal myocardial work. Detailed notes on these medications can be found in the section "Therapy of new onset and refractory heart failure". Dogs with dilated cardiomyopathy often further require management of supraventricular or ventricular arrhythmias. In general, supraventricular arrhythmias are treated with agents that slow conduction through the atrioventricular node while malignant ventricular arrhythmias are managed with either mexiletine +/- atenolol or sotalol. Caution must be exercised with many of these drugs because of their negative inotropic properties.

Prognosis

There is no cure for most dogs with dilated cardiomyopathy. If taurine deficiency is identified and corrected, myocardial function does often improve dramatically. Dogs with echocardiographic evidence of decreased myocardial contractility, but with no clinical signs of congestive heart failure, may live for a very long period of time. However, most affected dogs die as a result of the disease within 6 months to 2 years. Some very ill dogs improve to a remarkable degree with treatment and live a comfortable existence for months or years. Others dogs do not survive the initial 48 hours of hospitalization. Unfortunately, there is no reliable way to predict which dogs will respond to treatment. A generally worse prognosis has been reported in Doberman pinschers with DCM while a generally better prognosis has been noted in Cocker spaniels. Reported survival rates at 1 have varied between 3% and 54% in different studies (the highest percentage has been reported in Irish Wolfhounds).

Selected recent references

O'Grady MR, O'Sullivan ML, Minors SL, Horne R. Efficacy of benazepril hydrochloride to delay the progression of occult dilated cardiomyopathy in Doberman Pinschers. J Vet Intern Med. 2009 Sep-Oct;23(5):977-83.

Martin MW, Stafford Johnson MJ, Celona B. Canine dilated cardiomyopathy: a retrospective study of signalment, presentation and clinical findings in 369 cases. J Small Anim Pract. 2009 Jan;50(1):23-9.

O'Grady MR, Minors SL, O'Sullivan ML, Horne R. Effect of pimobendan on case fatality rate in Doberman Pinschers with congestive heart failure caused by dilated cardiomyopathy. J Vet Intern Med. 2008 Jul-Aug;22(4):897-904.