Restrictive Cardiomyopathy - Feline Cardiomyopathies

Overview

Restrictive cardiomyopathy (RCM) is a series of acquired pathologies of the feline myocardium. The common element is marked diastolic dysfunction without major alteration of systolic function. In RCM, the compliance and distensibility of the ventricular walls is reduced (ventricles are stiff), such that filling of the ventricles in diastole is compromised. This ultimately reduces the amount of blood that the left ventricle (LV) can accept. During the rapid filling phase of diastole, the pressure within the LV rises abruptly, preventing the entry of additional blood from atrial contraction in late diastole. This consequently increases left atrial pressure and the diameter of the left atrium or both atria. Grossly, RCM is characterised by a normal or near-normal appearance of the ventricles with dilation of the left atrium or both atria. The echocardiographic appearance of the cardiac chambers 2D images of cats with early RCM may be normal; however severe diastolic dysfunction may be evident from M-mode and Doppler imaging.

Aetiology

In humans, RCM is usually secondary to systemic infiltrative pathologies (e.g. amyloidosis, sarcoidosis) or radiation exposure; with pathology localized at the myocardial or endomyocardial level. Cats may also have myocardial and endomyocardial forms of RCM, but this seems to occur as a primary cardiomyopathy in cats. However, endomyocardial fibrosis has been associated with viral, hypereosinophilic and immune-mediated pathologies in rare cases.

Pathophysiology

The ventricular chambers appear normal or nearly normal, but are restricted in accepting diastolic filling due to the reduced compliance and rigidity of the ventricular walls.

Under normal physiological conditions, diastole can be divided into four phases:

1. Isovolumetric relaxation

2. Rapid ventricular filling

3. Slow ventricular filling (diastasis)

4. Atrial contraction

Ventricular filling is influenced by ventricular relaxation, ventricular compliance, atrial contraction and the pressure gradient between the left and right ventricles. The intraventricular pressure gradient is important as it causes an 'untwisting' at the cardiac apex in early diastole; which has a suction effect contributing to ventricular filling.

In RCM, reduced ventricular compliance and distensibility increases the final diastolic pressure, resulting in enlargement of the left atrium. Increased left atrial pressure has a knock-on effect of increased pressure in the pulmonary veins; thus leading to left-sided congestive heart failure (CHF). Tachycardia, associated with icreased sympathetic drive in cardiac dysfunction, contributes to disease progression. Coronary blood flow to the myocardium usually occurs during diastole, tachycardia results in a shorter period of diastole; therefore coronary blood flow is reduced. Reduced myocardial perfusion stimulates myocardial fibrosis, which contributes to rigidity and poor compliance of the ventricles. Finally, the increased atrial pressure and reduced atrial function results in slow blood flow within the atria. This may result in thrombus formation and, in some cases, embolisation of the clot to cause arterial thromboembolism (ATE).

Clinical Signs

The clinical presentation of cats with RCM, as with other cardiomyopathies, is extremely variable. There may be a long preclinical phase during which the cat remains asymptomatic. Early signs of cardiac dysfunction, such as exercise intolerance, often goes undetected in cats due to their sedentery nature. Cats with RCM are rarely identified in the asymptomatic phase. Cats with RCM frequently develop congestive heart failure (CHF), arterial thromboembolism (ATE) and are predisposed to arrhythmias.

Physical Examination

• May be completely normal
• Low intensity systolic murmur, sternal or left parasternal
• Gallop rhythm
• Tachyarrythmia
• Signs of congestive heart failure
• Arterial thromboembolism (ATE)

Left-sided Congestive Heart Failure

• Dyspnoea, tachypnoea, crackles (pulmonary oedema)
• Dyspnoea, restrictive pattern (fast,shallow breathing), muffled heart and ventral lung sounds (pleural effusion)

Right-sided Congestive Heart Failure

• Jugular pulse
• Hepatojugular reflux
• Occasionally ascites

Arterial Thromboembolism

The enlarged left atrium, stasis of blood within the left atrium, and reduced atrial function predispose to thrombus formation, and emboli may result. Typically these cases present with paresis or paralysis of one or both rear limbs due to occlusion at the aorta-iliac trifurcation. In some cases, emboli can involve other areas and can cause complex neurological manifestations, forelimb paralysis or acute renal ischemia.

Diagnosis

Radiography

Radiographs are useful for the diagnosis of congestive heart failure, however they are not able to distinguish the underlying cardiomyopathy. Radiographs may reveal left atrial dilation. On the dorso-ventral projection, a classic 'Valentine heart' shape may be evident due to the marked left atrial/biatrial dilation. Pulmonary venous conjestion, interstitial/alveolar pattern or the presence of a pleural effusion may be identified. These findings are not specific for RCM.

Echocardiography

This is the diagnostic test of choice for identification of RCM and excluding other cardiomyopathies.

Two-dimensional (2D) and M-mode

Imaging may reveal pronounced dilation of one or both atria and normal diameter and thickness of the ventricular chambers. Within the left atrium it is often possible to identify areas of spontaneous echo-contrast, reflecting blood stasis, or thrombi. The left atrium and the left auricular appendage should be carefully examined for this reason. It is useful to measure left auricular appendage flow velocity. Even in the absence of thrombi, evidence suggests that if velocity is <0.2 m/s on pulsed wave Doppler, the cat is at risk of thromboembolic complications.

Endomyocardial form of Restrictive Cardiomyopathy (eRCM)

This form of RCM is characterised by severe endomyocardial fibrosis with a 'bridging scar' crossing the left ventricle. This endomyocardial bridging scar may be associated with left ventricular obstruction during systole. In early forms, focal left ventricular hypertrophy may be evident, which over time progresses to the formation of a 'bridging scar'.

Myocardial form of Restrictive Cardiomyopathy (mRCM)

In this form of RCM, the left ventricle appears normal, but there is concurrent left atrial or biatrial enlargement.

Doppler echocardiography

Doppler is important to assess diastolic function. Mitral inflow and pulmonary venous inflow should be assessed from a left apical 4 chamber view.

Mitral Inflow

Mitral inflow is assessed by positioning the pulse wave Doppler sample volume between the tips of the open mitral valve leaflets. In the normal animal this demonstrates two phases:

• E wave (Early filling) which is a consequence of active relaxation of the left ventricle, and the pressure gradient between the left atrium and left ventricle.
• A wave (Atrial contraction) which corresponds to the P wave of the electrocardiogram (ECG).

This may be difficult to assess in cats, especially those with tachycardia, as the two waves may summate at fast heart rates. When the two separate phases can be identified, evidence of a restrictive filling pattern includes:

• E wave has a high velocity, but short deceleration time (DT). The E wave velocity is high due to high LA pressure. The poor compliance of the LV causes an abrupt deceleration of blood flow.
• A wave velocity is very low as a result of poor atrial function and poor compliance of the left ventrical. Therefore the LA is not able to contribute much to LV filling.

The E/A ratio is an index used to estimate diastolic function, an E/A >2 confirms a restrictive filling pattern and diastolic dysfunction.

Pulmonary Venous Flow

This is also useful to evaluate diastolic function; particularly when there is summation of the mitral E and A waves.

• During atrial systole (after the P wave of the ECG), blood flows retrograde from the left atrium to the plmonary vein. This produces the atrial reversal (Ar) wave.
• This is followed by the S wave, which indicates atrial blood flow during ventricular systole (between the QRS complex and the T wave). If the heart rate is slow enough, two waves may be observed: an early S wave (S1), which represents atrial relaxation, and the main S wave (late S wave or S2).
• During ventricular diastole, when the mitral valve is open, the left atrium allows pulmonary venous flow to reach the left ventricle, producing the D wave.

Evidence of restrictive filling pattern includes:

• Low S wave velocity
• High D wave velocity with rapid deceleration
• Ar wave velocity may be increased with adequate left atrial function, or reduced with severe atrial dysfunction.
• If the Ar wave duration exceeds the mitral A wave duration, this is evidence of increased left sided filling pressure.

Tissue Doppler Imaging (TDI)

This is a relatively recent technique in cats which is used to evaluate the speed of longitudinal movement of the myocardial walls during the different phases of the cardiac cycle. In normal cats, three waves can be identified:

• Positive systolic wave (Sm)
• Negative early diastolic wave (Em)
• Negative late diastolic wave (Am)

In normal cats, the Em velocity is higher than the Am velocity. In cats with diastolic dysfunction and impaired ventricular relaxation (as in the case of RCM), The Em velocity may be markedly reduced. Note that impaired ventricular relaxation is also identified as a normal aging change in cats; therefore cautious interpretation is required with elderly cats.

Treatment

Treatment should aim to control clinical signs of congestive heart failure (CHF) and aim to prevent arterial thromboembolism (ATE).