Management of the cat with heart failure

Introduction

Feline patients with cardiomyopathies other than hypertrophic cardiomyopathy (HCM), often referred to as non-hypertrophic cardiomyopathies (nhCM), rarely present to the veterinarian with preclinical disease. This is because examination during the preclinical phase is usually unremarkable, in contrast to the frequency of heart murmur detection in the cats with preclinical HCM. Cats with nhCM or end-stage HCM may present in different ways and with a variety of signs, but because they are sedentary and excellent at hiding subtle illness from their owners, the clinical onset in an affected cat may be acute. Signs can be linked to congestive heart failure (mainly severe dyspnea), cardiogenic shock (with weakness and hypotension), aortic thromboembolism (with severe pain and loss of use of one or more limbs), or arrhythmias (which may result in weakness, syncope or sudden death).

Management of the patient is directed towards the presenting problem(s), and this article will mainly address these strategies. Once the patient is stable, further investigations, especially echocardiography, should give the diagnosis of the primary cardiomyopathy, but this may not significantly affect the palliative management in most cases. Investigations should actively exclude other systemic conditions which may result in a cardiomyopathy phenotype and clinical presentation, such as hyperthyroidism, systemic hypertension, acromegaly, transient myocardial thickening, myocardial infiltration (e.g., lymphoma), myocardial infarction, tachycardia induced cardiomyopathy etc. It is beyond the scope of this article to discuss these further, but these conditions must be actively excluded. The article will then briefly review current guidance on the diagnosis of the primary cardiomyopathies other than HCM in cats 1,2 and how they are identified echocardiographically.

Congestive heart failure (CHF)

Cats with CHF typically present with severe dyspnea, usually because of fulminant pulmonary edema and/or pleural effusion. Pleural effusion in cats can be due to left-sided, right-sided or biventricular CHF, and is important to recognize (e.g., via thoracic point of care ultrasound (T-POCUS) during triage on presentation) as thoracocentesis is both lifesaving and of diagnostic purpose. The pleural effusion associated with CHF is usually a modified transudate, but it may be chylous. During T-POCUS, left atrial (LA) size should be subjectively determined; if it appears normal, it is highly unlikely that the dyspnea is associated with CHF. The presence of B-lines (hyperechoic radial lines within the lung-field, indicating a mix of fluid- and air-filled alveoli) in association with LA enlargement is most likely to reflect cardiogenic pulmonary edema (Figure 1). Decompensation into fulminant pulmonary edema may be precipitated by a stressful event, anesthesia, intravenous fluid administration or steroid administration. Decompensation of an existing cardiomyopathy may also be associated with concurrent illness, especially if this results in volume overload or high output states (e.g., anemia, hyperthyroidism). Cats with predominantly right-sided CHF (R-CHF) (ascites, pleural effusion and (very rarely) subcutaneous edema) are more likely to have arrhythmogenic right ventricular cardiomyopathy, but it is possible in other cardiomyopathies with myocardial failure. Examination of the jugular veins is informative; distension and the hepatojugular reflux is consistent with R-CHF, but a large volume of pleural effusion (even non-cardiogenic) can also result in jugular distension in this species.

Emergency treatment of pleural effusion

When there is dyspnea due to significant pleural effusion, this must be drained. Sedation may not be required, but if the cat is very anxious or stressed, butorphanol (Table 1a and b) can be beneficial. Supplemental oxygen should be provided. Ideally, the assessment and procedure should be carried out with the cat sitting in sternal recumbency. Clip and aseptically prepare one side of the chest at the costochondral junction, around the 7^th-8^th intercostal space; the site can be ultrasound guided. Using a 21G butterfly catheter attached to a three-way tap or one-way centesis valve and a 10 mL syringe, perform thoracocentesis. Local anesthetic can be used but generally causes more discomfort that directly inserting the butterfly needle into the chest. At least 300 mLs of effusion can usually be removed, and one-sided thoracocentesis will normally drain the pleural effusion adequately, but if needed, the opposite side can also be drained.

Retain some fluid for total protein, nucleated cell count and cytological and other evaluation, especially at initial presentation. Cats are likely to have concurrent pulmonary edema, so treatment with diuretics is essential.

Emergency treatment of pulmonary edema

Not all cats with pulmonary edema will have pulmonary auscultation abnormalities such as crackles, but if auscultation identifies a murmur, diastolic gallops or an arrhythmia, this is suggestive of CHF. T-POCUS identifies LA enlargement and B-lines. The dyspneic cat is very fragile, and gentle, stress-free handling is required to assist stabilization prior to investigations; butorphanol may be given for anxiolytic benefit. Provide the cat with flow-by oxygen or place in an oxygen cage as soon as initial triage and treatment have been completed. If cardiogenic pulmonary edema is strongly suspected, give furosemide (which administered intravenously has an initial venodilator effect, reducing preload) and repeat as required while monitoring respiratory rate and effort.

Addition of nitroglycerine (glyceryl trinitrate; GTN) may be considered. It is a venodilator, so preload reduction and decreasing left atrial pressure may help alleviate pulmonary edema. If there are signs of myocardial failure or cardiogenic shock, pimobendan IV or dobutamine as a constant rate infusion can be considered (see cardiogenic shock section). Table 1a and b summarize all drugs and doses.

Table 1a. Suggested drugs and doses for treatment of feline cardiomyopathy manifestations.

Chronic management of feline CHF

There is very little evidence for treating cats with CHF, so knowledge is typically extrapolated from what we know in other species 3. Other than furosemide, most drugs used to manage feline cardiomyopathies are not licensed in the species or for the treatment of CHF (Table 1a and b). However, there is anecdotal evidence and expert opinion supporting use of some of these drugs. Using the ABCD classification, cats with CHF are Stage C. Stage D is refractory CHF 1.

Compliance (feline or owner) is frequently an issue when medicating cats. It is therefore important that the priority of each drug is clear to the client – e.g., diuretics are essential, other drugs may not be. The more drugs prescribed, the less compliance is likely to be, and the clinician needs to consider this, especially when there is limited evidence supporting many of the drugs used.

Diuretics

Diuretics are essential in the management of CHF, and will be required long term for most stable cats once acute decompensation has been treated, with furosemide being most commonly prescribed. During chronic therapy, the furosemide dose should be slowly down-titrated, with home-monitoring of sleeping respiratory rate (SRR), to aim for the minimum effective daily dose which controls clinical signs. The dose should be up-titrated if the owner notes a persistent increase in SRR. Cats with severe CHF may require high doses of furosemide, so the dose range is considerable. As a ceiling-loop diuretic, it results in loss of chloride, sodium and potassium (with water) in the renal tubules, so pre-renal azotemia and hypokalemia may subsequently develop. In cats with pre-existing chronic kidney disease (CKD), the addition of pre-renal with renal azotemia is problematic. As a minimum monitoring check, serum urea, creatinine and electrolytes should be evaluated one-week post-furosemide dose increase. Hypokalemia may result in weakness or worsen the risk of arrhythmias. Hypochloremia is an expected side effect of furosemide. Hyponatremia does not usually occur, unless there is intense neuroendocrine activation associated with severe CHF or as a consequence of furosemide administration. Hyponatremia is dilutional, as a consequence of high vasopressin resulting in free water retention.

Drugs to counteract neuro-endocrine activation

Although much less studied than in other species, reduced cardiac output will result in neuro-endocrine activation, which results in progression of CHF. Initially, reduced blood pressure results in sympathetic stimulation, with beta-receptor stimulus resulting in tachycardia, increased myocardial contraction and increased risk for arrhythmias. Alpha-receptor stimulation will result in vasoconstriction, increasing pre- and after-load. Renin release and activation of the renin-angiotensin-aldosterone system (RAAS) ultimately results in angiotensin II and aldosterone release. Both angiotensin II and aldosterone result in myocardial remodeling and fibrosis. Angiotensin II is a potent vasoconstrictor and triggers increased vasopressin and endothelin release. Aldosterone causes increased sodium and water retention and the CHF syndrome. There is evidence for RAAS activation in cats with HCM or after therapy with some drugs, including furosemide 4. Therefore, in cats with CHF requiring furosemide, it is logical to also start treatment to counteract the RAAS system, such as an angiotensin-converting enzyme (ACE) inhibitor (e.g., benazepril) or an angiotensin II receptor (AT1) blocker (e.g., telmisartan) and/or an aldosterone antagonist (spironolactone). However, evidence is currently lacking that ACE-inhibitors influence progression of feline cardiomyopathies or survival time 5. One study suggested a possible benefit in cats with CHF receiving enalapril, but this was not statistically significant 6. Most of the feline cardiomyopathies result in diastolic heart failure, which in human medicine also lacks strong evidence about efficacy of treatments other than diuretics.

Telmisartan (AT1 blocker) is licensed in some countries for feline renal disease, but so far no studies have reported its use for CHF, although evidence in cats suggest a favorable effect on RAAS 7. A palatable liquid formulation facilitates medicating cats if counteraction of RAAS is indicated.

The aldosterone antagonist spironolactone is a mild diuretic, counteracting sodium and water retention. Spironolactone made no difference to diastolic function or ventricular mass in Maine Coons with preclinical HCM 8 but in contrast, one small study in cats with cardiomyopathy and CHF, all receiving furosemide and benazepril, suggested that the addition of spironolactone reduced morbidity and mortality 9.

Inotropic support and balanced vasodilation

Pimobendan (Table 1a and b) is an inodilator drug, which improves pump function by calcium sensitization and phosphodiesterase III inhibition. It is also a balanced vasodilator, reducing afterload and preload, and improves myocardial function without increasing myocardial oxygen consumption. It is indicated in cardiomyopathies associated with impaired systolic function, especially dilated cardiomyopathy 10,11. Positive inotropes and arteriodilator drugs are theoretically contraindicated in HCM with left ventricular outflow tract obstruction (LVOTO), since the combination of increased contraction and arteriodilatation may increase the severity of LVOTO. However, a retrospective case-control study of cats treated with CHF associated with HCM including some with LVOTO showed an increased survival time in cats receiving pimobendan 12. LVOTO did not result in increased adverse events in another study 13; in contrast, a prospective study failed to show any survival benefit for cats with CHF receiving pimobendan 14.

Pimobendan may improve LA function, which may in turn reduce the risk for thromboembolic complications 15, and it has been reported to inhibit platelet aggregation, although this may only be at doses much higher than the clinical recommendation 16.

Diltiazem is licensed in some countries to treat feline HCM and has been advocated as a treatment to improve diastolic function, but interim analysis of one study showed no additional benefit of diltiazem compared with furosemide alone 6,17. Its major indication is an antiarrhythmic drug (Table 1a and b).

Beta blockers

If a cat is receiving beta-blockers (e.g., for previously diagnosed HCM with LVOTO), the dose should be carefully down-titrated or even stopped after a few weeks. This is because the intense neuroendocrine activation of CHF includes increased sympathetic drive to maintain cardiac output; beta-blockade may prevent some of this compensatory effort. However, the decision about discontinuing beta-blockers depends on each individual case (e.g., if there is significant LVOTO). Beta-blockers should never be started in a cat presenting with uncontrolled CHF; an interim analysis of heart failure treatments indicated significantly reduced survival in cats receiving this class of drug 6.

What about refractory CHF?

In a cat with poorly controlled or recurrent CHF signs that is already receiving a high dose of furosemide, an underlying end-stage cardiomyopathy is likely. If the cat is in R-CHF, bowel edema may lead to impaired absorption of oral medications, as well as development of cardiac cachexia. Briefly, some options for refractory CHF (Table 1a and b) include:

• Swap furosemide for torasemide, a much more potent ceiling loop diuretic with higher bioavailability; it may only need to be given once a day and is well tolerated 18. The total daily dose of furosemide can be divided by 10 (or 20) for a starting dose of torasemide, but renal function and electrolytes must be monitored since the risk of causing acute kidney injury is high.
• Consider sequential nephron blockade with the addition of hydrochlorothiazide (often combined with amiloride). This can be especially useful in refractory R-CHF.
• Optimize all CHF medication, including addition of pimobendan, ACE-inhibitors, and spironolactone.

What about cats with CKD and CHF?

A cat with concomitant CKD may become more azotemic if relatively high doses of furosemide are required to manage its CHF. This is a grave prognostic indicator, as the cat tends to see-saw between uncontrolled CHF and worsening azotemia, depending on the dose of furosemide. It often prompts euthanasia if a balance cannot be achieved.

It is not uncommon in the cat with severe CHF requiring high initial cumulative furosemide doses to control the CHF to cause an acute kidney injury. Backing off the furosemide dose and delaying the introduction of ACE-inhibitors should resolve this. In a cat with CHF who becomes azotemic, fluid therapy should be avoided, as this will increase preload and further decompensate the CHF. Instead, diuretics should be reduced or stopped for a short period while monitoring respiration.

Table 1b. Suggested drugs and doses for treatment of feline cardiomyopathy manifestations.

Cardiogenic shock

Cardiogenic shock may be seen in cats presenting with severe or end-stage cardiomyopathies, often in association with CHF. As a presentation, it is much less common when compared with CHF, but it may be precipitated by development of hemodynamically significant arrhythmias. It represents a major reduction in cardiac output and peripheral perfusion; owners report severe exercise intolerance and lethargy. On examination a cat is weak, with evidence of reduced perfusion; pallor, slow capillary refill, cold extremities and hypothermia. The cardinal sign is systemic hypotension (e.g., systolic blood pressure <100 mmHg). In CHF and its associated neuro-endocrine activation, including vasoconstrictors, all with the homeostatic priority of maintaining systemic blood pressure, it can be appreciated that hypotension is a grave prognostic indicator.

If cardiogenic shock is identified, as well as treating the CHF, positive inotropic support is indicated, preferably with pimobendan because of its inodilator effect. Dobutamine constant rate infusion (CRI) can also be used in the emergency setting, provided there is constant ECG and other monitoring available (Table 1a and b).

Feline Arterial Thromboembolism (FATE)

Cats with severe cardiomyopathies associated with LA dilatation and impaired LA function are at increased risk for formation of cardiac thrombi and subsequent systemic thromboembolism. This can be anywhere along the arterial tree, but typically distal aortic emboli result in severe pain, paralysis, loss of associated pulse (e.g., femoral artery), pallor (e.g., nail beds), and cold extremity of affected limbs. Muscles (e.g., gastrocnemius) are often contracted and painful on palpation. In some cases, acute presentation with thromboembolism can be the first sign of an underlying cardiomyopathy, and an important management goal in cardiomyopathy is to reduce the risk of FATE, especially if the LA is very dilated, reduced in function, or if any actual thrombus or spontaneous echocontrast (“smoke”) is evident on echocardiography. It is beyond the scope of this article to discuss FATE in depth, but strategies to treat or prevent it include one or more of the anti-thrombotic (anti-platelet) drugs (e.g., clopidogrel, aspirin) and/or anticoagulant drugs (e.g., dalteparin (low molecular weight heparin), rivaroxaban or apixaban (Table 1a and b)). There does not appear to be any advantage (and there may be increased risks) for using clot-busting drugs such as tissue plasminogen activator (tPA) 19. Instead, conservative medication drives the cat’s own fibrinolysis system and prevents further platelet activation and aggregation. Cyproheptadine may reduce serotonin-mediated vasoconstriction of collateral vessels. Analgesia is imperative (usually opiates such as methadone). For prevention, clopidogrel is again indicated 20 (Table 1a and b).

Arrhythmias

Arrhythmias are common in feline myocardial disease and indicate a worse prognosis for survival 21. Ventricular arrhythmias may arise because of increased wall stress, myocardial ischemia, or fibrosis which provides a substrate for re-entry arrhythmias. Atrioventricular blocks, including constant or paroxysmal complete atrioventricular block, may also reflect fibrosis. Atrial stretch may result in atrial (supraventricular) premature complexes or atrial fibrillation. Tachyarrhythmias will compromise diastolic function, with less time for diastolic filling, which leads to increasing filling pressures and decompensation into CHF. Antiarrhythmic therapy may be warranted in these cases (Table 1a and b). Both brady- and tachyarrhythmias may impair cardiac output, leading to clinical signs such as lethargy or syncopal episodes. Malignant arrhythmias may result in sudden death, which may be the presenting sign in some cardiomyopathic cats.

Classification of the other feline cardiomyopathies

Cats with most of the nhCMs (or end-stage HCM) will present with clinical signs described above and require to be managed for their presenting problem(s). However, the exact classification may be unimportant, as the presenting clinical problems must be addressed by treatment. The diagnosis of the actual underlying cardiomyopathy is typically based on echocardiographic phenotype, but classification of the specific non-hypertrophic cardiomyopathy (nhCM) is fraught with difficulties, and it is quite possible to have differing opinions given for the same cat and same images, although a recent consensus statement has provided useful guidance 1. In particular, the diagnosis of end-stage HCM (where regression of left ventricular hypertrophy may reflect cardiomyocyte loss and fibrous replacement), restrictive cardiomyopathy and non-specific cardiomyopathy may differ between individual cardiologists. The echocardiographic diagnosis represents that point in time; unless the cat was evaluated earlier in its disease, it cannot be known whether the cat started off with HCM before becoming end-stage. A brief description of the criteria to diagnose a specific nhCM 2, with some representative echocardiographic images, is as follows.

1. End-stage hypertrophic cardiomyopathy. Although HCM is by far the most common cardiomyopathy, it may present in its end-stages with a different phenotype. This term is used if there was known prior HCM, even though there may be no segmental or generalized left ventricular hypertrophy, or the hypertrophy is very mild. The left ventricle may be hypokinetic or dilated (Figure 2) and myocardial infarction may be evident (Figure 3).

2. Restrictive cardiomyopathy (RCM). Non-hypertrophied, non-dilated and associated with left or biatrial dilatation (Figure 4) with diastolic dysfunction, RCM shows a restrictive filling pattern, characterized by transmitral E wave velocity being more than twice the A wave velocity. Note this form of diastolic dysfunction is not specific for RCM but can occur in any of the cardiomyopathies. It is subdivided into a myocardial form 22, where the endocardium is unremarkable (Figure 4), and an endomyocardial form 23,24, where the endocardium can be irregularly thickened and echogenic, with bridging scars which may result in intra-ventricular obstruction (Figure 5). Siamese or oriental breeds may be predisposed.

3. Non-specific cardiomyopathy (previously called unclassified cardiomyopathy) 2. Here the echocardiography features do not easily fit into the other cardiomyopathy criteria (e.g., systolic and diastolic dysfunction without left ventricular dilatation or increased hypertrophy) or there may be mixed features of other cardiomyopathies (Figure 6). 

4. Dilated cardiomyopathy (DCM) 2. Originally associated with taurine deficiency but now uncommon, but with a possible genetic or nutritional component (e.g., grain-free diets) when it occurs nowadays. Echocardiography can show a dilated left ventricle in systole (>12 mm) and diastole (>18 mm), and subjectively thin LV walls. The phenotype might also represent an end-stage of other cardiomyopathies (Figure 7).

5. Arrhythmogenic right ventricular cardiomyopathy (ARVC) 25. Cases typically present with predominantly R-CHF signs and a dilated right heart. However, left ventricular function is often impaired. It may be associated with ventricular or other arrhythmias. In contrast to dogs or humans with ARVC, complete atrioventricular block can occur. Birman cats are predisposed (Figure 8).

Conclusion

Classification of the different feline cardiomyopathies is fraught and there are no robust echocardiographic guidelines – the phenotype at the time of echocardiographic examination is described, but this may not be the original phenotype. However, the most important point is that the problem(s) identified at the clinical presentation should be addressed with treatment, and the therapeutic approach is similar regardless of the actual classification of the cardiomyopathy.