Challenges in Feline Cardiology

Challenges in Feline Cardiology

 

HEART DISEASE IN CATS
Heart disease is highly prevalent in cats, with multiple studies confirming that the most common group of acquired feline cardiac disease, the cardiomyopathies, affect approximately 1 in 8 healthy cats.   With the AVMA reporting that there were over 74 million cats owned in the US in 2012, that represents at least 9 million cats with cardiac disease in the US alone.  While a notable proportion of cats with cardiac disease have a normal life expectancy and do not experience adverse consequences of their disease, cats with a severe or advanced disease have a high morbidity and mortality from heart failure, sudden death or arterial thromboembolism.  Identifying those cats at high risk for adverse consequences of their disease and treating them appropriately remain two of the biggest challenges in feline cardiology.  Unfortunately, there is little consensus among practitioners and cardiologists regarding the ‘best’ way.  This reflects the difficulties faced with diagnosing and classifying cardiac disease in cats, the high prevalence of functional murmurs in cats, and the paucity of evidence to support the benefit of therapy for both preclinical cardiomyopathies and cats with heart failure.

DIAGNOSING FELINE HEART DISEASE
Cardiomyopathies are the most common form of heart disease in cats.  Prevalence data from studies over the past 15 years show that hypertrophic cardiomyopathy (HCM) with or without dynamic outflow tract obstruction (HCM with dynamic outflow tract obstruction is also known as hypertrophic obstructive cardiomyopathy or HOCM) is by far the most common heart disease, followed by restrictive or unclassified cardiomyopathies (RCM or UCM) and dilated cardiomyopathy (DCM).

The most common screening tool for heart disease in cats is auscultation with a stethoscope.  This can identify a heart murmur, and occasionally gallop sounds or abnormal heart rhythms, as a possible indicator of heart disease.  In the largest study of overtly healthy cats, approximately 40 % of cats have heart murmurs.  More interestingly, only approximately 1 in 3 of those asymptomatic cats with heart murmurs had heart disease (Payne et al, 2015), with the majority of cats with heart murmurs (2 out of 3) having benign or physiological flow murmurs.  This indicates that the presence of a heart murmur in a cat is not an accurate indicator that heart disease is present.  The absence of a heart murmur does not necessarily mean the absence of cardiac disease.  In fact, in an observational study from general practice of cats presenting with respiratory signs, the presence of a gallop or an arrhythmia were far more accurate predictors of heart failure than the presence of a murmur or tachycardia (Smith & Dukes-McEwan, 2012).

When a cat presents with clinical signs and physical examination findings that suggest cardiac disease, further investigations are necessary.  These could include blood testing, thoracic radiography, ECG or echocardiography.  Of these, blood tests for NT-proBNP and echocardiography are the most useful.  NT-proBNP is an easily accessible and relatively cheap screening test for helping to determine whether a cat has preclinical heart disease or heart failure.  Cats with elevated NT-proBNP have a high likelihood of having cardiac disease and therefore should undergo echocardiography.  Echocardiography is the gold standard diagnostic test for detecting and classifying feline cardiomyopathies, but as a truly accurate diagnostic test, it is limited to specialists.  It is worth noting the elevations in NT-proBNP are not 100% specific for cardiac disease.  They can also occur in cats with kidney disease, dehydration, chronically high blood pressure (hypertension) and hyperthyroidism.

MANAGING FELINE HEART DISEASE
There is a lack of peer-reviewed evidence to support the benefit of any therapy at any stage of feline heart disease.  Consequently, decisions for management are almost entirely based on extrapolation from recommendations in human disease, theoretical benefits, or anecdote.  A published survey of cardiology specialists and clinicians with an interest in cardiology in 2011 showed a very wide variety of prescribing practices for cats with HCM/HOCM (Rishniw & Pion, 2011).  This study supports the observation that there is not a single accepted way to manage heart disease in cats, even among cardiologists.  To this end, I will present the published evidence to date, as well as the accepted methods for managing HCM/HOCM in humans.

MANAGING PRECLINICAL DISEASE
Preclinical heart disease occurs when heart disease is present but the patient does not have any symptoms.  In cats, this is usually suspected when a heart murmur, abnormal heart rhythm or enlarged heart is suspected.  This is usually the stage of heart disease that has the longest duration, often lasting for several years.

Beta-blockers (Atenolol) and Calcium Channel blockers (Diltiazem)
Historically, veterinarians have prescribed Beta-blockers (Atenolol, Propranolol), or non-dihydropyridine Calcium Channel Blockers (Diltiazem, Verapamil) for cats with preclinical HCM, particularly with the obstructive form of HCM (HOCM).  This is mainly based on the theoretical ability of these drugs to decrease the severity of outflow obstruction, and their historical use in humans with HCM/HOCM.  However, studies in cats and humans with HCM/HOCM have not shown a convincing benefit on survival.  Almost 30 years ago, a very small clinical trial that evaluated 3 of these drugs: Diltiazem, Propranolol, and Verapamil.  They were administered to 17 cats with HCM/HOCM and clinical signs.  The study reported that cats receiving Diltiazem had an improved clinical response in the short term when compared to cats receiving Propranolol or Verapamil (Bright et al, 1991).  However, this study had many limitations that render the validity of these results in the general population questionable.  As a result of this, the lack of observed benefit for Diltiazem in clinical cases, the high incidence of side effects of Diltiazem (anorexia, vomiting), and the need to dose up to three times daily, it has since lost favor among cardiologists for cats with HCM/HOCM.

Following the initial enthusiasm for Diltiazem, atenolol has become the favored drug of most cardiologists for cats with the obstructive form of HCM (HOCM).  As with Diltiazem, it has a number of theoretical benefits.  It has also been shown to actually decrease the severity of outflow obstruction in cats with preclinical HOCM (Jackson et al, 2015).  However, a prospective non-randomized controlled study showed no benefit for the Atenolol to improve 5-year survival versus receiving no therapy in cats with preclinical HCM or HOCM (Schober et al, 2013).  However, despite the disappointing results from clinical trials, there may still be a role for Atenolol in feline HCM/HOCM.  It is established that humans with HOCM and severe obstruction (>4 m/s) have an increased risk for death, even if they have no clinical signs of their HOCM.  That increased risk is almost entirely eliminated if their obstruction is resolved with surgical myectomy (removal of a portion of the ventricular muscle).  Unfortunately, such surgical options are not feasible or available in cats.  However, since atenolol has been shown to decrease the severity of obstruction in cats, it is reasonable to consider that it might improve survival in some cats with HOCM.

Enalapril, Benazepril, and Spironolactone
There have been conflicting reports of the effects of angiotensin-converting enzyme (ACE) inhibitors (Enalapril, Benazepril) on selected echocardiographic variables in cats with HCM and one prospective randomized placebo-controlled trial that showed no change in echocardiographic measurements of diastolic function and LV mass in Maine Coons with HCM treated with Spironolactone (Macdonald et al, 2008).  Importantly, the primary endpoints of all of these studies have been imaging measurements of cardiac dimensions and function, which have been assessed after a relatively short time (≤1 year).  Such endpoints are surrogate markers of disease severity and may not correlate with clinical outcome.  There have not been any studies demonstrating a beneficial effect of role Enalapril, Benazepril or Spironolactone on clinical outcomes such as quality of life or mortality.  The role Enalapril, Benazepril and Spironolactone in treating feline cardiomyopathies, therefore, remains unknown.

MANAGING HEART FAILURE
Cats with heart failure have heart disease that is resulting in clinical signs that affect their quality of life.  Common signs are lethargy/hiding behavior, decreased appetite, and breathing difficulties.  Cats with heart failure a reduced length of life, which for most cats is less than 1 year.  Management of this stage of the disease is vital to improve quality of life.

Diuretics (Lasix, Aldactazide, Torasemide)
There is an expert consensus in humans, dogs, and cats that diuretics are an efficacious therapy for fluid retention accompanying heart failure.  Consequently, clinical trials to assess the efficacy of diuretics in cats with heart failure are not likely to be approved by any ethical review committee.  Furosemide (Lasix) is the most commonly used diuretic of the most potent diuretic group (loop diuretics).  It is always indicated for any cat with suspected or confirmed heart failure and unlike other diuretics, can be given by injection as well as in tablet form, making it ideal for cats with acute, life-threatening heart failure as well as treating for the longer term at home.  For cats with mild heart failure, it may only need to be given by mouth once daily.  For cats with more severe heart failure, it needs to be given up to three times daily.  For cats with heart failure that is refractory (no longer responsive to) to Furosemide (Lasix), Hydrochlorothiazide/Spironolactone (Aldactazide) can be beneficial when given in addition to Furosemide (Lasix) and given once or twice daily.  Another option is to replace Furosemide (Lasix) with Torasemide (Torsemide), which is also a loop diuretic, but with additional actions.  Torasemide is typically started at a dose of 1/10th to 1/13th the total daily dose of Furosemide (Lasix) that the cat is already receiving and given once daily.  Diuretics are also appropriate to treat small volumes of fluid in the chest cavity (pleural effusion) and abdomen (ascites).  For cats with moderate to large volumes of pleural effusion or ascites, direct and immediate removal of the fluid with a needle (thoracocentesis, abdominocentesis) are recommended first.

Other heart failure therapies
One study has prospectively compared an ACE inhibitor, Diltiazem, and a Beta-blocker on mortality in 118 cats with a variety of cardiomyopathies (HCM/HOCM, RCM, UCM), heart failure and receiving Furosemide (Lasix) (Fox, 2003). There was no benefit for any therapy over Furosemide (Lasix) alone and a possible harm for Beta-blocker administration.  While this is unpublished research it remains the only randomized placebo-controlled clinical trial to evaluate the effect of these therapies on mortality in cats with cardiomyopathies and heart failure.  Cats with DCM were not evaluated.  A recent retrospective non-randomized controlled study showed a survival benefit for receiving Pimobendan (Vetmedin) over not receiving Pimobendan in 32 cats with non-taurine-responsive DCM and heart failure (Hambrook & Bennett, 2012).  For cats with DCM caused by taurine deficiency, it has been known for 30 years that this can be treated with taurine supplementation.  While the datasheet for Pimobendan (Vetmedin) lists hypertrophic cardiomyopathy as a labeled contraindication to its use, observational studies have reported that Pimobendan is well tolerated in cats with other cardiomyopathies and heart failure.  Furthermore, a small, retrospective study of cats with HCM/HOCM and heart failure reported a median survival time of 20 months for cats that received Pimobendan, versus <4 months for cats that did not receive Pimobendan (Reina-Doreste et al, 2014).  At a minimum, these findings warrant further investigation of Pimobendan in cats with heart failure.  Many cardiologists, including the author, use Pimobendan (Vetmedin) in cats with heart failure on a regular basis for several years and have not noted adverse effects.  The question of whether Pimobendan is harmful to cats with HOCM and severe obstruction is as yet unanswered.  Ultimately, until there is convincing evidence of a benefit for any therapy in addition to Furosemide (Lasix) to treat heart failure in cats, it remains very appropriate to treat with Furosemide alone, particularly for cats that experience their first episode of heart failure.  The author treats many feline heart failure cases with Furosemide alone.

MANAGING ARTERIAL THROMBOEMBOLISM
Arterial thromboembolism (ATE) can be a devastating consequence of cardiomyopathy in cats, resulting in paresis, paralysis or end-organ damage.  Oral anti-clotting drugs (Aspirin, Clopidogrel) and injectable anti-clotting drugs (unfractionated heparin, low molecular weight heparins) are often administered in an attempt to prevent (thromboprophylaxis) or treat ATE; the latter in addition to pain relief, supportive care and treatment of heart failure as required.  Therapy and dosing is based on extrapolation from human medicine and evidence of drug effects on laboratory measurements of platelet or coagulation function, usually in healthy cats.  A prospective multi-center clinical trial comparing the efficacy of Aspirin (81 mg PO q72h) and Clopidogrel (Plavix) (18.75 mg PO q24h) for prevention of ATE recurrence in cats in cats with cardiac disease and prior ATE reported a significant survival benefit for Clopidogrel (Hogan et al, 2015).  It is not known whether this result can be extrapolated to the prevention of thrombus formation in cats that have cardiac disease but have not experienced an ATE episode yet.  Nevertheless, given the painful and catastrophic effects on quality of life of an ATE episode, the author routinely prescribes Clopidogrel (Plavix) for cats with recognized echocardiographic indicators for increased ATE risk.  These include severe left atrial dilatation, poor systolic function, spontaneous echocardiographic contrast and intracardiac thrombus.  This highlights the need for echocardiography to evaluate ATE risk in any cat with suspected cardiac disease.  A newer oral antiplatelet drug, the factor Xa inhibitor, Rivaroxaban (Xarelto), is currently the subject of a clinical trial in cats, comparing its ATE prevention efficacy with that of clopidogrel.

Echocardiographic images of the Feline Cardiomyopathies

Capture

Key:

  1. Hypertrophic Cardiomyopathy / Hypertrophic Obstructive Cardiomyopathy (HCM/HOCM)
  2. Dilated Cardiomyopathy (DCM)
  3. Restrictive Cardiomyopathy (RCM)
  4. Endomyocardial Fibrosis Restrictive Cardiomyopathy (EMF-RCM)
  5. Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)
  6. Unclassified Cardiomyopathy (UCM)

Submitted by:

Simon Dennis BVetMed, MVM, MRCVS, DECVIM (Cardiology)

 

REFERENCES

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https://www.sciencedirect.com/science/article/pii/S1760273415000958

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https://www.sciencedirect.com/science/article/pii/S1760273415000429

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https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1939-1676.2006.tb00707.x

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