Restrictive cardiomyopathy (RCM) can be defined as an acquired pathology of the feline myocardium; more accurately, it refers to a series of pathologies which have as a common element marked diastolic dysfunction without major alteration of the systolic function (1). The term “restrictive” refers to functional rather than anatomical characteristics but there is still much to investigate about the etiology of this disease. RCM reduces the compliance and distensibility of the ventricular walls, altering the ventricular diastolic filling and reducing the quantity of blood that the left ventricle (LV) can accept. During the rapid filling phase, the diastolic pressure of the left ventricle rises abruptly, counteracting the entry of additional quantities of blood, in particular later in diastole, associated with atrial contraction. This in turn increases the left atrial pressure and the dimensions of the left atrium (or both atria). Anatomically, RCM is characterized by the normal or near-normal appearance of the ventricles and by a slight increase in the septal and left ventricular free (posterior) wall thicknesses, contrasting with the pronounced left atrial dilation; this, the normal or near-normal LV chamber diameter and volume, and the near-normal systolic function exclude other cardiomyopathies. The echocardiographic appearance of the cardiac chambers in static two-dimensional images of cats with early RCM (i.e. without obvious anatomical alterations) may be normal: however severe diastolic pathophysiology may be evident from M-mode and Doppler profiles. Recently, Doppler was used to identify very early anomalies in diastolic function (2) using human cardiology guidelines (3).
In man, restrictive cardiomyopathy is more often secondary to systemic 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.
The myocardial form is typically non-infiltrative, with little or no thickening of the ventricular wall. The endomyocardial form is characterized by the progressive infiltration of fibrous tissue, predominantly in the left ventricle, causing adhesions of the endocardium, which has an irregular appearance (4). The etiology is essentially unknown, although endomyocardial fibrosis associated with viral, hypereosinophilic, and immune-mediated pathologies has been reported.
As mentioned previously, the ventricular chambers appear either normal, slightly reduced, or slightly enlarged (especially where there is an infiltrationtype pathology) 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 consecutive phases, all regulated by active mechanisms:
1. Isovolumetric relaxation
2. Rapid ventricular filling
3. Diastasis (slow ventricular filling)
4. Atrial contraction
Ventricular filling is determined by ventricular relaxation, ventricular compliance, atrial contraction and the intraventricular pressure gradient (5). This last is one of the factors responsible for the active suction mechanism in the normallyfunctioning ventricle; the apical “untwisting” movement in the early phase of diastole causes suction that contributes to ventricular filling. This mechanism is significantly altered and reduced in myocardial pathologies. The diminished ventricular compliance and the reduced movement of the left ventricular wall increases the final diastolic pressure, with enlargement of the left atrium and increased left atrial and pulmonary vasculature pressures leading to left sided congestive heart failure (6). Tachycardia further worsens the picture because it reduces coronary blood flow; reduced myocardial perfusion stimulates fibrosis which further increases myocardial rigidity. In addition the increased left atrial pressure and reduced function slows the intra-atrial flow and predisposes to thrombus formation.
The clinical presentation of cats with RCM is extremely variable. As in many other heart disorders there may be a long preclinical phase during which there are no outward signs; the sedentary nature of cats does not help, as it is difficult to identify intolerance to physical exercise. Sometimes the factor which precipitates the development of symptoms can be a mundane situation which induces rapid release of catecholamines; e.g. hospitalizing a cat for routine surgery can cause tachycardia and increased systemic pressures.
Many cats present with acute pulmonary edema and are severely dyspneic, which may mask the underlying pathology. Any diastolic gallops, arrhythmias or evidence of pulmonary edema should prompt additional investigations to diagnose cardiac disease. Many cats present in left sided congestive failure with typical signs including tachypnea/ dyspnea and soft inspiratory crackles indicative of pulmonary edema. Cardiac auscultation may detect a murmur but can be normal. Pleural effusionmay develop, which muffles both heart and lung sounds. In some cases there may be distension or pulsation of the jugular veins and a positive hepatojugular reflux.
Another acute presentation may be due to systemic 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.
On radiographs left atrial dilation (Figures 1,2) may be seen whilst the dimensions of the ventricular chambers appear normal. In the dorso-ventral projection a classic “Valentine’s heart”, due to marked left or biatrial enlargement, may be evident, although this is not specific for RCM versus other cardiomyopathies. Congestion of the pulmonary vessels, the interstitial/alveolar pattern, and the presence of pleural effusion (which can obscure the cardiac silhouette) can all make the diagnosis more difficult.
The echocardiogram is the method of choice for diagnosis since it allows rapid, non-invasive investigation; it enables measurement of parameters and indices that allow recognition and staging of the diastolic dysfunction by identifying the myocardial pathology responsible. Other cardiomyopathies or cardiac disease can be excluded.
Two-dimensional and M-mode echocardiographic imaging enables evaluation of myocardial thickness and can be suggestive and characteristic of RCM, especially if there is pronounced dilation of one or both atria and normal dimensions of the ventricular chambers but impaired ventricular relaxation and compliance (7). Within the left atrium it is often possible to identify areas of spontaneous echo-contrast, reflecting blood stasis, or thrombi. The right parasternal long axis 4 chamber view shows the dilation of the left (and possibly also the right) atrium (Figures 3,4). The normal or near-normal ventricular diameter and wall thicknesses can be confirmed; the lack of hypertrophy tends to exclude other cardiomyopathies. Sometimes an irregular hyperechoic appearance of the ventricular endocardium may be noted, which can enlarge sufficiently to cause intraventricular obstruction.
The left atrium and its appendage should be carefully examined, especially as the severity of left atrial dilation enhances the risk of thromboembolism. The left auricular appendage is best visualized from the left cranial view, cranial to the pulmonary artery (8). Thrombus material and spontaneous echocontrast are readily imaged (Figure 5). This view is also used to measure left auricular appendage flow velocity. Even in the absence of thrombi, if velocity is <0.2 m/s on pulsed wave Doppler, the cat is at risk of thromboembolic complications.
Doppler echocardiography is important to assess diastolic function and identify restrictive filling patterns. Although tricky to obtain in cats, the left apical 4 chamber view is desirable to assess mitral inflow and pulmonary venous flow.
• Mitral inflow, or transmitral filling, is assessed by positioning the pulse wave Doppler sample volume between the tips of the open mitral valve leaflets. This reveals the mitral inflow pattern, which in the normal animal in sinus rhythm demonstrates two phases of filling:
- E wave (Early filling) which is a consequence of active relaxation of the left ventricle, and the left atrium - ventricle pressure gradient.
- A wave (Atrial contraction) which corresponds to the P wave of the ECG.
Note that in many cats, especially with accentuated tachycardia due to congestive heart failure, the two waves may summate, so the mitral inflow pattern may not be easy to interpret. When separate, however, evidence of a restrictive filling pattern is gained when (i) the mitral E wave has a high velocity but short deceleration time (DT) and (ii) the A wave velocity is very low. Mitral E wave velocity is high because of high left atrial filling pressure. The poor compliance of the left ventricle abruptly decelerates this flow. Atrial dysfunction and the poor compliance of the left ventricle together explain the low A wave velocity. Cardiologists use the E/A ratio as an index to estimate diastolic function; if E/A >2 this confirms restrictive filling (Figure 6).
• Pulmonary venous flow (PVF) also provides useful information for evaluating left ventricular filling, particularly when there is summation of the mitral E and A waves. The PVF pattern is as follows:
- During atrial systole (after the P wave of the ECG), there is retrograde flow in the pulmonary vein from the left atrium, producing the Ar wave.
- This is followed by the S wave, which primarily indicates atrial blood flow during ventricular systole (between the QRS complex and the T wave); if a cat is not tachycardic two waves may be noted, an early S wave (S1) - which indicates 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 include low S wave and high, rapidly decelerating D wave velocity (Figure 7). The Ar wave velocity may be increased with adequate left atrial function (as in Figure 7), 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 (9).
Comparison of the transmitral and pulmonary venous flow profiles allows a cardiologist to distinguish restrictive filling such as seen in RCM from other myocardial pathologies with a restrictive profile (10). A restrictive filling pattern with marked left atrial dilation and virtually normal ventricles are classic indicators of RCM (11).
Among the other methods currently employed in cats to assess diastolic function, color M-mode and Tissue Doppler echocardiography should be mentioned.
Color M-mode Doppler allows assessment of the mitral inflow propagation velocity (Vp); measuring blood flow as it courses from the mitral annulus towards the apex, it is represented as a slope. Diastolic function determines velocity; the poorer the diastolic function, the shallower the slope. In humans with RCM, Vp is reduced; this has not been reported in the veterinary literature but the author has noted a similar trend in cats with RCM compared to normal cats (Figure 8).
Tissue Doppler (TD) has recently been used in cats to evaluate the speed of longitudinal movement of the myocardial walls during the different phases of the cardiac cycle (12,13). As in any Doppler technique, it is critical to be aligned with the longitudinal fibers of the wall under interrogation. In normal subjects, the TD profile presents a positive systolic wave (Sm) and two negative diastolic waves, Em (early) and Am (late). In healthy, non-aged individuals, the Em velocity is higher than the Am velocity. In the presence of impaired relaxation (e.g. RCM) the Em velocity may be markedly reduced (Figure 9) (14). Expressing the E wave and Em velocities as a ratio (E/Em) allows estimation of left sided filling pressures (15).
A summary of the restrictive profiles seen with the different techniques is shown in Figure 10.
Prognosis and treatment
Cats presenting with RCM usually have advanced disease and the long term prognosis is therefore poor. The treatment of RCM should aim to control the clinical signs of left-sided congestive heart failure, with additional radiographic and echocardiographic monitoring as appropriate. The acute management of dyspneic cats includes thoracocentesis if there is significant pleural effusion, and furosemide for pulmonary edema, with the drug administered (preferably IV) at 2-4 mg/kg every 1-2 hours until the clinical picture improves. Ongoing therapy depends on the response to treatment but ideally the interval between doses can be increased and if the cat is compliant, oral medication may be employed. Although there is no evidence of efficacy of any drug in feline RCM, calcium channel blockers have been reported to improve lusitropy (i.e. ventricular relaxation) and are often the drug of first choice. As these cases are at high risk of thromboembolic complications (and especially if echocardiographic indicators of risk are recognized) anti-platelet medication such as aspirin or clopidogrel should also be considered (Table 1). Treatment of chronic congestive heart failure in cats should include furosemide and an ACE inhibitor. Prognosis is also dependent on the willingness of the cat to take oral medication, and owner compliance in administering it.
The diagnosis of RCM requires a systematic approach and is both demanding and complex. It involves integrated interpretation of the different echocardiographic profiles and the information gathered from clinical examination. This is essential to establish both the therapeutic process and the prognosis; the latter basically depends on not only the seriousness and the progression of the myocardial structural alteration, but on early therapeutic intervention and its success.
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