Diseases Of The Middle And Inner Ear

Normal Anatomy and Physiology

The middle ear consists of the tympanic membrane, three cavities (epitympanic, tympanic, and ventral), and the bony ossicles (malleus, incus, and stapes). The tympanic membrane has two parts: (1) the thin pars tensa that attaches to the manubrium of the malleus and (2), above the pars tensa, the thicker, pars flaccida. The main portion of the middle ear, the ventral tympanic bulla, has two compartments in the cat (ventromedial and dorsolateral). The air-filled bulla is lined with modified respiratory epithelium, which is either squamous or cuboidal and may be ciliated. The four openings in the middle ear are the (1) tympanic opening, (2) the vestibu-lar window, (3) the cochlear window, and (4) the ostium of the auditory tube. The auditory tube is the communication between the middle ear and caudal nasopharynx. The normal flora of the middle ear may be due to this pharyngeal communication, but the role of the auditory tube as a source of bacteria in otitis media is unknown. The tympanic opening is a common source of bacterial infection of the middle ear in dogs with otitis extema. The cochlear and vestibular windows are possible ports of entry for progression of otitis media or ototoxic substances into the inner ear.

Cranial nerve VII, or the facial nerve, the sympathetic innervation of the eye, and the parasympathetic innervation of the lacrimal gland are closely associated with the middle ear. The separation of the facial nerve from the middle ear is minimal along the rostral aspect of its course through the petrosal bone. The nerve supplies motor fibers to the superficial muscles of the head, the muscles of the external ear, the caudal belly of the digastricus, and the ossicular muscles. The nerve also supplies sensation of the vertical ear canal and concave surface of the pinna.

Postganglionic sympathetic nerve fibers course closely with those of the facial nerve to innervate the smooth muscles of the eye. Preganglionic parasympathetic fibers also pass through the middle ear to innervate the salivary and lacrimal glands.

The inner ear is located within the petrosal bone. The cochlea, vestibule (saccule and utricle), and semicircular canals form the membranous labyrinth, which is encased in bone, called the bony labyrinth. The vestibular system functions to maintain the position of the eyes, trunk, and limbs relative to the position of the head, responding to linear and rotational acceleration and tilting. The system consists of the saccule, utriculus, and semicircular canals and communicates with the middle ear via the vestibular window. Fluid within the semicircular canals tends to remain stationary during motion, bending the cilia of the cells in the utricle and saccule, causing depolarization. These stereocilia synapse with the dendrites of the vestibular portion of the eighth cranial nerve and the signal is conducted via cranial nerve VIII to vestibular nuclei in the myelencephalon, the spinal cord, centers in the cerebellum and cerebral cortex, and motor nuclei of cranial nerves III, IV, and VI. The result is coordination of the body, head, and eye movement. Projections to the vomiting centers are responsible for nausea and vomiting associated with vestibular disorders and motion. The cochlear system, involved with the translation of sound, consists of the spiral organ, or organ of Corti, cochlear duct, scala vestibule, and scala tympani. Transmission of sound through the tympanic membrane, ossicles, and cochlear window results in undulation of the basilar membrane of the spiral organ. Cilia bend and cause depolarization and transmission of a signal to cochlear nuclei, caudal colliculi, and cerebral cortex. The cochlear nuclei control reflex regulation of sound via projections to cranial nerves V and VII, which control the muscles of the ossicles. Other projections allow for conscious perception of sound.

Otitis Media

Neoplasia of the Middle Ear

Neoplasia of the middle ear is rare; most cases represent extension of tumors originating in the external ear canal.

Inflammatory Polyps

Inflammatory polyps are a non-neoplastic admixture of inflammatory and epithelial cells originating in the tympanic bulla in cats. Other sites of origin include the auditory tube and nasopharynx. Macrophages, neutrophils, lymphocytes, plasma cells, and epithelial cells are usually present on histopathologic examination. The cause is unknown, but ascending infection and congenital causes have been suggested. No age or sex predilection exists for the condition, but younger cats are more commonly affected (1 to 5 years of age). Signs can be unilateral or bilateral and depend on the location of the mass lesion. A single polyp can grow into the external ear canal, down the auditory tube into the nasopharynx, or both. Signs of concurrent otitis extema and media are common with polyps limited to the ear, but respiratory stridor, dyspnea, gagging, and dysphagia occur with growth into the pharynx.

Diagnosis is based on otoscopic and pharyngeal examinations. Radiographs of the bulla, nasal cavity, and pharynx may be considered, and CT or MRI can be used to diagnose the site and side of origin of inflammatory polyps/ Treatment consists of excision by traction or surgical excision via ventral bulla osteotomy. Regrowth is a problem in half of the cats treated by traction extraction alone, and Homer’s syndrome is common in cats after ventral bulla osteotomy.

Otitis Interna

Otitis interna is usually an extension of otitis media or neoplasia of the middle ear. A careful neurologic examination is imperative to the localization of vestibular signs. Clinical signs associated with otitis interna include head tilt, ataxia, horizontal or rotary nystagmus, circling or falling toward the side of the lesion, or ipsilateral nystagmus. The fast phase of nystagmus is usually away from the side of the lesion. Occasionally, animals will become nauseated or vomit. Homer’s syndrome or deficits in cranial nerve VII may accompany otitis media interna, but involvement of other cranial nerves, vertical or changing nystagmus, or the presence of conscious proprioceptive deficits or paresis indicate central rather than peripheral vestibular disease. Bilateral peripheral vestibular disease is rare, but the animal will not have a head tilt, nystagmus, or strabismus and may exhibit wide head excursions and a crouched stance or the inability to stand.

The diagnosis of otitis interna is based on history, clinical signs, and physical, neurological, and otoscopic examinations. Advanced imaging may be helpful in distinguishing the anatomic location of the disease process. Treatment with aggressive medical or surgical intervention appropriate to the localization is important in prevention of adjacent brain stem involvement.

Prognosis for Otitis Media and Interna

A fair prognosis can be given if aggressive surgical and medical therapy are possible. Cases with concurrent severe external ear canal changes require total ear canal ablation and lateral bulla osteotomy. Repeated infections after ventral bulla osteotomy or total ear canal ablation and lateral bulla osteotomy may be operated again with resolution of the condition. Resistant organisms, failure to respond to aggressive surgery, and significant osteomyelitis are associated with a poor prognosis. The neurologic signs associated with otitis media and interna may be permanent, but many animals learn to use visual cues and can compensate for vestibular deficits. Facial nerve deficits, Horner’s syndrome, and keratoconjunctivitis sicca are often permanent.


Ototoxic substances (Table Ototoxic Drugs) damage the cochlear or vestibular systems or both. Otic application of medication can also cause adverse effects through local inflammation of the tympanic membrane or the meatal window (or both), as well as resultant otitis media. Topical medications also cause adverse effects by systemic absorption. Ototoxic substances reach the inner ear after local application and absorption through the cochlear or vestibular windows or hematogenously. The most frequent cause of ototoxicity is the application of an ototoxic substance to the external ear canal in a pet with a ruptured tympanum, which results in distribution to the middle ear. Absorption by the inner ear is increased when inflammation of the cochlear window occurs with otitis media. Hematogenous distribution of otoioxins to the inner ear is inherent in some medications (e.g. aminoglycosides).

Ototoxic Drugs

Aminoglycoside Antibiotics Antiseptics
Neomycin Chlorhexidine
Dihydrostreptomycin Iodine & iodophores
Gentamicin Ethanol
Streptomycin Benzalkonium chloride
Kanamycin Benzethonium chloride
Tobramycin Cantrimide
Amikacin Antineoplastic Agents
Other Antibiotics Cisplatin
Polymixin B & E Nitrogen mustard
Minocycline Miscellaneous
Erythromycin Quinine
Chloramphenicol Solicylates
Vancomycin Propylene glycol
Loop Diuretics Detergents
Furosemide Arsenic
Bumetanide Lead
Ethacrynic acid Mercury

The development of ototoxicity also depends on the vehicle of the preparation, chemical composition, drug concentration, concurrent medications, as well as the route, frequency, and duration of administration. Examples of increased risk of ototoxicity depending on the vehicle (e.g. combination of chlorhexidine and detergents) and concurrent medications (e.g. loop diuretics and aminoglycosides) have been described. Minimization of the risk of toxicity should be considered when any potentially toxic substance is administered either topically or systemically. The integrity of the tympanic membrane should be known prior to topical administration of any potentially ototoxic drug, and consequences of each drug should be considered in light of the animal’s health and concurrent therapies.

Idiopathic Vestibular and Facial Nerve Diseases

A complete neurologic examination is key to differentiating peripheral from central vestibular disorders. Head tilt, ataxia, horizontal or rotary nystagmus, and cranial nerve VII deficits may be seen with either condition. Central vestibular disease causes paraparesis, conscious proprioceptive deficits, other cranial nerve abnormalities, and vertical or changing nystagmus. Middle ear neoplasia, otitis media interna, idiopathic vestibular syndrome, and congenital vestibular disorders result in peripheral vestibular signs. Congenital vestibular disorders have been described in the German shepherd, Doberman pinscher, English cocker spaniel, Siamese, and Burmese breeds. Bilateral congenital vestibular syndrome has been described in beagles and Akitas. Clinical signs of head tilt and ataxia in these dogs and cats may be persistent or may improve; animals can be congenitally deaf.

Otitis media interna may be associated with facial paresis or paralysis if cranial nerve VII is affected by the inflammation. Otitis should be ruled out before diagnosing any animal with idiopathic facial nerve paralysis, because otitis requires aggressive management and the idiopathic condition can only be treated symptomatically or with acupuncture.


Acquired Late-Onset Conductive Deafness

Conductive deafness is due to lack of transmission of sound through the tympanic membrane and ossicles to the inner ear. Conditions that block sound transmission through the external ear canal, tympanic membrane, or middle ear and ossicles, such as otitis externa, otitis media, and otic neoplasia, cause conductive deafness. Less common causes of conductive deafness include trauma-induced fluid accumulation in the middle ear, atresia of the tympanum or ossicles, fused ossicles, or incomplete development of the external ear canal, which results in fluid accumulation in the middle ear. An increase in hearing threshold, absence of air-conducted hearing, and the presence of bone-conducted hearing on BAER suggest conductive deafness. The application of a bone-anchored hearing aid was described in one dog with conductive deafness after total ear canal ablation. It maintained bone-conducted hearing and tolerated the hearing aid anchored to the parietal bone Use of a bone-anchored device was required, because the dog did not have an external ear canal in which to place an earpiece. The hearing aid acted as an amplifier, and the dog seemed to respond to its use.

Acquired Late-Onset Sensorineural Deafness

Presbycusis, or decline in hearing associated with aging, may be due to one of the following: loss of hair cells and degeneration in the organ of Corti, degeneration of spiral ganglion cells or neural fibers of the cochlear nerve, atrophy of the stria vascularis, or changes in the basilar membrane. Because this condition occurs in older dogs and cats from 8 to 17 years of age, animals should be evaluated for concurrent causes of conductive deafness such as chronic otitis extema or media and otic neoplasia. BAER testing may demonstrate normal waveforms in response to high-intensity sound. If conduction is intact at an increased hearing threshold, use of an amplifying hearing aid may be beneficial. Pets may not tolerate occlusive types of ear pieces often used in hearing aids, and training to the ear piece should be done prior to application of the hearing aid.

Ototoxic substances, chronic exposure to loud noise, hypothyroidism, trauma, and bony neoplasia can also cause acquired late-onset deafness in dogs and cats. Ototoxicity can result in abolition of waveforms or an increase in hearing threshold on BAER. BAER testing can be used to re-evaluate patients for return of function after withdrawal of medication after exposure to ototoxic medication.

Congenital Sensorineural Deafness

Inherited sensorineural deafness usually results in complete loss of hearing in the affected ear by 5 weeks of age. Many breeds can be affected with the condition (Box Canine Breeds Associated with Inherited Deafness). The condition has been linked to coat color in many breeds of dogs and white cats. The condition is common in white cats, and mode of inheritance is thought to be autosomal dominant with incomplete penetrance.The condition is most common in white cats with blue irides. The correlation of white coat, blue eyes, and deafness is not perfect, but cats with two blue irides have a greater risk of deafness than cats with one blue iris, which have a greater risk of deafness than cats without blue irides. Total hearing loss occurs more often in longhaired white cats. The condition is common in certain breeds of dogs, such as dalmatians, which have a nearly 30% incidence of deafness (combining unilateral and bilateral deafness).

Canine Breeds Associated with Inherited Deafness

Akita Ibizan hound
American-Canadian shepherd Italian greyhound
American cocker spaniel Jack Russell terrier
American Eskimo Kuvasz
American Staffordshire terrier Labrador retriever
Australian cattle dog Maltese
Australian shepherd Miniature pincer
Beagle Miniature poodle mongrel
Bichon frise Norwegian dunkerhound
Border collie Nova Scotia duck tolling retriever
Borzoi Old English sheepdog
Boston terrier Papillion
Boxer Pit bull terrier
Bulldog Pointer
Bull terrier Poodle (toy & miniature)
Catahoula leopard dog Puli
Chihuahua Rhodesian ridgeback
Chow chow Rottweiler
Collie Saint Bernard
Dachshund Schnauzer
Dalmatian Scottish terrier
Doberman pincer Sealyham terrier
Dogo Argentino Shetland sheepdog
English cocker spaniel Shropshire terrier
English setter Soft-coated Wheaton terrier
Foxhound Springer spaniel
Fox terrier Sussex spaniel
French bulldog Tibetan spaniel
German shepherd Tibetan terrier
Great Dane Walker American foxhound
Great Pyrenees West Highland white terrier
Greyhound Yorkshire terrier

The trait is associated with the dominant merle or dapple gene in collies, Shetland sheepdogs, Great Danes, and dachshunds. The incidence of deafness tends to increase with increasing amount of white in the coat, and dogs homozygous for the merle gene are usually deaf and may be solid white, blind, or sterile, The piebald or extreme piebald gene is associated with deafness in dalmatians, bull terriers, Great Pyrenees, Sealyham terriers, greyhounds, bulldogs, and beagles. Inheritance is thought to be autosomal recessive, but the trait may be polygenic.

Heterochromia irides and lack of retinal pigment are associated with white color in dogs and cats. Hearing loss may be associated with absence of pigment in the cochlear stria vascularis. Diminished blood supply and disorders of endolymph production, with changes in the chemical or mechanical properties of endolymph, lead to degeneration of the organ of Corti secondary to stria vascularis atrophy. Loss of hair cells and abnormalities of the cochlear duct, Reissner membrane, tectorial membrane, and internal spiral suicus are typical of cochleosaccular type of end-organ degeneration seen in these cases.,

Clinical signs of deafness may be recognized in puppies as young as 3 weeks of age by astute owners; definitive diagnosis of uni- or bilateral deafness is usually made by BAER testing at 5 to 6 weeks of age when the auditory system is completely developed and cochlear degeneration, if present, is complete.

Congenital Acquired Sensorineural Deafness Exposure to bacteria, ototoxic drugs, low oxygen tension, and trauma in utero or during the perinatal period rarely causes deafness in young animals.


Amiodarone HCL (Cordarone, Pacerone)

Class III Antiarrhythmic

Highlights Of Prescribing Information

Antidysrhythmic agent that can be used in dogs for arrhythmias associated with left ventricular dysfunction or to convert atrial fib into sinus rhythm; very limited experience warrants cautious use

May be useful in horses to convert atrial fib or V tach into sinus rhythm

Contraindicated in 2nd, 3rd degree heart block, bradyarrhythmias

In DOGS: GI disturbances (vomiting, anorexia) most likely adverse effect, but neutropenia, thrombocytopenia, bradycardia, hepatotoxicity, positive Coombs’ test reported

In HORSES: Limited use, accurate adverse effect profile to be determined; Hind limb weakness, increased bilirubin reported when used IV to convert atrial fib

Many drug interactions

What Is Amiodarone HCL Used For?

Because of its potential toxicity and lack of experience with use in canine and equine patients, amiodarone is usually used when other less toxic or commonly used drugs are ineffective. It may be useful in dogs and horses to convert atrial fib into sinus rhythm and in dogs for arrhythmias associated with left ventricular dysfunction. In horses, one horse with Ventricular tachycardia was converted into sinus rhythm using amiodarone.

As the risk of sudden death is high in Doberman pinschers exhibiting rapid, wide-complex ventricular tachycardia or syncope with recurrent VPC’s, amiodarone maybe useful when other drug therapies are ineffective.


Amiodarone’s mechanism of action is not fully understood; it apparently is a potassium channel blocker that possesses unique pharmacology from other antiarrhythmic agents. It can be best classified a Class III antiarrhythmic agent that also blocks sodium and calcium channels, and beta-adrenergic receptors. Major properties include prolongation of myocardial cell action-potential duration and refractory period.


Amiodarone may be administered parenterally or orally. Amiodarone is widely distributed throughout the body and can accumulate in adipose tissue. Amiodarone is metabolized by the liver into the active metabolite desethylamiodarone. After oral administration of a single dose in normal dogs, amiodarone’s plasma half-life averaged 7.5 hours, but repeated dosing increased its half-life from 11 hours to 3.2 days.

In horses, amiodarone has a low oral bioavailability (range from 6-34%) and peak levels of amiodarone and desethylamiodarone occur about 7-8 hours after an oral dose. After IV administration amiodarone is rapidly distributed with a high apparent volume of distribution of 31 L/kg. In horses, amiodarone is relatively highly bound to plasma proteins (96%). Clearance was 0.35 L/kg/hr and median elimination half-lives for amiodarone and desethylamiodarone were approximately 51 and 75 hours, respectively ().

In humans, oral absorption is slow and variable, with bioavailabilities ranging from 22-86%. Elimination half-lives for amiodarone and desethylamiodarone range from 2.5-10 days after a single dose, but with chronic dosing, average 53 days and 60 days, respectively.

Before you take Amiodarone HCL

Contraindications / Precautions / Warnings

Amiodarone is considered contraindicated in patients (humans) hypersensitive to it, having severe sinus-node dysfunction with severe sinus bradycardia, 2nd or 3rd degree heart block, or bradycardial syncope.

Clinical experience in veterinary patients is limited. Consider use only when other less toxic and more commonly used drugs are ineffective.

Adverse Effects

Gastrointestinal effects (e.g., anorexia, vomiting) are apparently the most likely adverse effects seen in the limited number of canine patients treated. Hepatopathy (bilirubinemia, increased hepatic enzymes) has been reported in dogs on amiodarone. Because hepatic effects can occur before clinical signs are noted, routine serial evaluation of liver enzymes and bilirubin is recommended. Other adverse effects reported in dogs include bradycardia, neutropenia, thrombocytopenia, or positive Coombs’ test. During IV infusion, pain at injection site, and facial pruritus and hyperemia have been noted. Corneal deposits may be seen in dogs treated with amiodarone, but this affect apparently occurs less frequently in dogs than in humans.

In human patients, adverse effects are very common while on amiodarone therapy. Those that most commonly cause discontinuation of the drug include: pulmonary infiltrates or pulmonary fi-brosis (sometimes fatal), liver enzyme elevations, congestive heart failure, paroxysmal ventricular tachycardia, and thyroid dysfunction (hypo- or hyperthyroidism). An odd effect seen in some individuals is a bluish cast to their skin. Reversible corneal deposits are seen in a majority of humans treated with amiodarone.

Clinical experience in dogs is limited; the adverse effect profile of this drug in people warrants its use in veterinary patients only when other less toxic agents are ineffective and treatment is deemed necessary.

Reproductive / Nursing Safety

In laboratory animals, amiodarone has been embryotoxic at high doses and congenital thyroid abnormalities have been detected in offspring. Use during pregnancy only when the potential benefits outweigh the risks of the drug. In humans, the FDA categorizes this drug as category D for use during pregnancy (There is evidence of human fetal risk, hut the potential benefits from the use of the drug in pregnant women may he acceptable despite its potential risks.)

Overdosage / Acute Toxicity

Clinical overdosage experience is limited; most likely adverse effects seen are hypotension, bradycardia, cardiogenic shock, AV block, and hepatotoxicity. Treatment is supportive. Bradycardia may be managed with a pacemaker or beta-1 agonists (e.g., isoproterenol); hypotension managed with positive inotropic agents or vasopressors. Neither amiodarone nor its active metabolite are dialyzable.

How to use Amiodarone HCL

Note: Some human references state that because of the potential for drug interactions with previous drug therapies, the life-threatening nature of the arrhythmias being treated, and the unpredictability of response from amiodarone, the drug should be initially given (loaded) over several days in an inpatient setting where adequate monitoring can occur.

Amiodarone HCL dosage for dogs:

For conversion of atrial fibrillation:

a) At the time of writing (2007) one case report () and one retrospective evaluation () have been published using amiodarone to convert atrial fibrillation in dogs. Dosage recommendations are yet to be fully defined; monitor the current literature for further recommendations.

For recurrent ventricular tachycardia not controlled with other less toxic drugs:

a) 10-25 mg/kg PO twice daily for 7 days, followed by 5-7.5 mg/kg PO twice daily for 14 days, followed by 7.5 mg/kg PO once daily ()

b) For ventricular arrhythmias secondary to occult cardiomyopathy in Doberman pinschers: 10 mg/kg PO twice daily for one week and then 8 mg/kg PO once daily. For severe V-Tach, mexiletine is added at 5-8 mg/kg three times daily for one week. Once efficacy confirmed, patient weaned off mexiletine. ()

c) Amiodarone as above in “b”, but after 6 months may be reduced to 5 mg/kg once daily. ()

d) 10-20 mg/kg PO q12h ()

Amiodarone HCL dosage for horses:

For conversion of atrial fibrillation or ventricular tachycardia: a) 5 mg/kg/hr for one hour, followed by 0.83 mg/kg/hr for 23 hours and then 1.9 mg/kg/hour for the following 30 hours. In the study (A fib), infusion was discontinued when conversion occurred or when any side effects were noted. 4 of 6 horses converted from A fib; one horse from V tach. In order to increase success rate and decrease adverse effects, regimen should be further adapted based upon PK/PD studies in horses. ()


■ Efficacy (ECG)

■ Toxicity (GI effects; CBC, serial liver enzymes; thyroid function tests; blood pressure; pulmonary radiographs if clinical signs such as dyspnea/cough occur)

Client Information

■ Because of the “experimental” nature (relatively few canine/equine patients have received this agent) and the toxicity dangers associated with its use, clients should give informed consent before the drug is prescribed.

Chemistry / Synonyms

An iodinated benzofuran, amiodarone is unique structurally and pharmacologically from other antiarrhythmic agents. It occurs as a white to cream colored lipophilic powder having a pKa of approximately 6.6. Amiodarone 200 mg tablets each contain approximately 75 mg of iodine.

Amiodarone HCL may also be known as: amiodaroni hydrochloridum, L-3428, 51087N, or SKF-33134-A; many trade names are available.

Storage / Stability/Compatibility

Tablets should be stored in tight containers, at room temperature and protected from light. A 3-year expiration date is assigned from the date of manufacture.

Injection should be stored at room temperature and protected from light or excessive heat. While administering, light protection is not necessary. Use D5W as the IV diluent. Amiodarone is reportedly compatible with dobutamine, lidocaine, potassium chloride, procainamide, propafenone, and verapamil. Variable compatibility is reported with furosemide and quinidine gluconate.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

The ARCI (Racing Commissioners International) has designated this drug as a class 4 substance. See the appendix for more information.

Human-Labeled Products:

Amiodarone Oral Tablets: 100 mg, 200 mg & 400 mg; Cordarone (Wyeth-Ayerst); Pacerone (Upsher Smith); generic; (Rx)

Amiodarone Concentrate for Injection (for IV Infusion): 50 mg/mL in 3 mL amps & vials; Cordarone (Wyeth-Ayerst); generic; (Rx)


Canine Heartworm Disease

Heartworm infection (HWI) (dirofilariasis), caused by Dirofilaria immitis, primarily affects members of the family Canidae. Dirofilariasis is widely distributed, being recognized in northern and southern temperate zones, in the tropics, and in the subtropics. Infections are recognized in most of the United States, although the distribution favors the Southeast and Mississippi River Valley. In some endemic areas in the United States, infection rates approach 45%, and in some hyperendemic tropical regions, virtually all dogs are infected. Dirofilariasis is generally infrequent in Canada. A recent survey of veterinarians indicated that in 2001 there were approximately 240,000 cases diagnosed in the United States.

Species known to have been infected with Dirofilaria immitis include the domestic dog, wolves, foxes, coyotes, domestic cats, ferrets, muskrats, sea lions, nondomestic cats, coatimundi, and humans. The species of greatest interest to die practicing veterinarian include the dog and domestic cat. Because the consequences, treatment, and prognoses differ between the two species, clinical aspects of canine and feline heartworm disease (HWD) will be discussed separately.

When heartworm infection is severe or prolonged, it may result in the pathologic process, called HWD. heartworm disease may vary from asymptomatic (radiographic lesions only) to severe, life-threatening, chronic pulmonary artery, lung, and cardiac disease. In chronic HWI, glomerulonephritis, anemia, and thrombocytopenia may also be recognized. Severe dirofilariasis may, in addition, produce acute and fulminant multisystemic presentations, such as caval syndrome (CS) and disseminated intravascular coagulation (DIC).

Life Cycle

Dirofilaria immitis is transmitted by over sixty species of mosquitoes, although important mosquito vectors probably number less than 12. Understanding the complex life cycle of Dirofilaria immitis is imperative for veterinary practitioners in heartworm endemic areas. Adult heartworms (L5) reside in the pulmonary arteries and, to a lesser extent in heavy infections, the right ventricle. After mating, microfilariae (LI) are produced by mature adult female heartworms (L5) and are released into the circulation. These LI are ingested by feeding female mosquitoes and undergo two moults (LI to L2 to L3) over an 8- to 17-day period. It is important to note that this process is temperature dependent; in times of the year when insufficient numbers of days occur in which the ambient temperature is adequate, moulting in the mosquito does not occur during the lifetime of the female mosquito and transmission cannot occur.The resultant L3 is infective and is transmitted by the feeding mosquito to the original or another host, most often a male dog. Another moult occurs in the subcutaneous, adipose, and skeletal muscular tissues shortly after infection (1 to 12 days), with a final moult to L5 3 months (50 to 68 days) after infection. This immature adult (1 to 2 cm in length) soon enters the vascular system, migrating to the heart and lungs, where final maturation (mature male adults range from 15 to 18 cm and females from 25 to 30 cm) and mating occur. Under optimum conditions, completion of the life cycle takes 184 to 210 days. The canine host typically becomes microfilaremic 6 to 7 months after infection. Microfilariae (LI), which are variably present in infected dogs, show both seasonal and diurnal periodicity, with greatest numbers appearing in the peripheral blood during the evening hours and during the summer. Adult heartworms in dogs are known to live up to 5 years and microfilariae up to 30 months. Dillon has recently emphasized that the disease process in heartworm disease begins with the moult to L5 (as soon as 2 to 3 months postinfection), at which time immature adults (L5) enter the vascular system, initiating vascular and possibly lung disease, with eosinophilia and eosinophilic infiltrates and signs of respiratory disease. It is important to note that this antedates the profession’s current ability to diagnose HWI.

Canine Heartworm Disease: Pathophysiology

Heartworm is a misnomer because the adult actually resides in the pulmonary arterial system for the most part, and the primary insult to the health of the host is a manifestation of damage to the pulmonary arteries and lung. The severity of the lesions and hence clinical ramifications are related to the relative number of worms (ranging from one to over 250), the duration of infection, and the host and parasite interaction. Immature and mature adult heartworms reside primarily in the caudal pulmonary vascular tree, occasionally migrating into the main pulmonary arteries, the right heart, and even the great veins in heavy infections.

Obstruction of pulmonary vessels by living worms is of little clinical significance, unless worm burdens are extremely high. The major effect on the pulmonary arteries is produced by worm-induced (toxic substances, immune mechanisms, and trauma) villous myointimal proliferation, inflammation, pulmonary hypertension (PHT), disruption of vascular integrity, and fibrosis.This may be complicated by arterial obstruction and vasoconstriction caused by dead worm thromboemboli and their products. Pulmonary vascular lesions begin to develop within days of worm arrival (as early as 3 months postinfection), With endothelial damage and sloughing, villous proliferation, and activation and attraction of leucocytes and platelets. The immigration of such cells and the release of trophic factors induce smooth muscle cell proliferation and migration with collagen accumulation and eventual fibrosis. Proliferative lesions eventually encroach upon and even occlude vascular lumina. Endothelial swelling with altered intracellular junctions increases the permeability of the pulmonary vasculature. Worms, which have died naturally or have been killed, elicit an even more severe reaction, inciting thrombosis, granulomatous inflammation, and rugous villous inflammation. Grossly, the pulmonary arteries are enlarged, thick-walled, and tortuous, with roughened endothelial surfaces. These changes are only partially reversible.

Although the role of exercise in exacerbation of the signs of thromboembolic heartworm disease is accepted, its role in the development of pulmonary vascular disease and pulmonary hypertension is less clear. Although Rawlings was unable to show an effect of 2.5 months controlled treadmill exercise on pulmonary hypertension in heavily infected dogs, Dillon showed more severe pulmonary hypertension in lightly infected, mildly exercised dogs than in more heavily infected but unexercised dogs receiving no exercise at 6 months postinfection.

Diseased pulmonary arteries are thrombosed, thickened, dilated, tortuous, noncompliant, and functionally incompetent, thereby resisting recruitment during increased demand; hence exercise capacity is diminished. Vessels to the caudal lung lobes are most severely affected. Pulmonary vasoconstriction results secondary to vasoactive substances released from heartworms. Furthermore, hypoxia (induced by ventilation-perfusion mismatching secondary to eosinophilic pneumonitis, pulmonary consolidation, or both), further contributes to vasoconstriction. The result is pulmonary hypertension and compromised cardiac output. Pulmonary hypertension is exacerbated with exercise or other states of increased cardiac output. The right heart, which is an efficient volume pump but does not withstand pressure overload, first compensates by eccentric hypertrophy (dilatation and wall thickening) and, in severe infections, ultimately decompensation (right heart failure). In addition, hemodynamic stresses, geometric changes, and cardiac remodeling may contribute to secondary tricuspid insufficiency, thereby complicating or precipitating cardiac decompensation. Pulmonary infarction is uncommon because of the extensive collateral circulation provided the lung and because of the gradual nature of vascular occlusion. Because of increased pulmonary vascular permeability, perivascular edema may develop. Although, along with an inflammatory infiltrate, this may be evident radio-graphically as increased interstitial and even alveolar density, in and of itself, it is seemingly of minimal clinical significance and does not indicate left heart failure (in other words, furosemide is not indicated).

Spontaneous or postadulticidal thromboembolization (PTE) with dead worms may precipitate or worsen clinical signs, producing or aggravating PHT, right heart failure or, in rare instances, pulmonary infarction. Dying and disintegrating worms worsen vascular damage and enhance coagulation. Pulmonary blood flow is further compromised and consolidation of affected lung lobes may occur. With acute and massive worm death, this insult may be profound, particularly if associated with exercise. Exacerbation by exercise likely reflects increased pulmonary artery flow with escape of inflammatory mediators into the lung parenchyma through badly damaged and permeable pulmonary arteries. Dillon has suggested that the lung injury is similar to that seen in adult respiratory distress syndrome (ARDS).

Pulmonary parenchymal lesions also result by mechanisms other than post-thromboembolic consolidation. Eosinophilic pneumonitis is most often reported in true occult HWD, when immune-mediated destruction of microfilariae in the pulmonary microcirculation produces amicrofilaremia. This syndrome results when antibody-coated microfilariae, entrapped in the pulmonary circulation, incite an inflammatory reaction (eosinophilic pneumonitis). A more sinister but uncommon form of parenchymal lung disease, termed pulmonary eosinophilic granulomatosis, has been associated with HWD. The exact cause and pathogenesis are unknown, but it is felt to be similar to HWD-related allergic pneumonitis. It is postulated that microfilariae trapped in the lungs are surrounded by neutrophils and eosinophils, eventually forming granulomas and associated bronchial lymphadenopathy.

Antigen-antibody complexes, formed in response to heart-worm antigens, commonly produce glomerulonephritis in heartworm-infected dogs. The result is proteinuria (albu-minuria) but uncommonly renal failure. Heartworms may also produce disease by aberrant migration. This uncommon phenomenon has been associated with neuromuscular and ocular manifestations, because worms have been described in tissues such as muscle, brain, spinal cord, and anterior chamber of the eye. In addition, arterial thrombosis with L5 has been observed when worms migrate aberrandy to the aortic bifurcation or more distally in the digital arteries. Adult heartworms may also migrate in a retrograde manner from the pulmonary arteries to the right heart and venae cavae, producing CS, a devastating process, described following.

Clinical Signs of Canine Heartworm Disease

The clinical signs of chronic heartworm disease depend on the severity and duration of infection and, in most chronic cases, reflect the effects of the parasite on the pulmonary arteries and lungs, and secondarily, the heart. It is important to point out that the vast majority of dogs with heartworm infection are asymptomatic. Historical findings in affected dogs variably include weight loss, diminished exercise tolerance, lethargy, poor condition, cough, dyspnea, syncope, and abdominal distension (ascites). Physical examination may reveal evidence of weight loss, split second heart sound (13%), right-sided heart murmur of tricuspid insufficiency (13%), and cardiac gallop. If right heart failure is present, jugular venous distension and pulsation typically accompanies hepatosplenomegaly and ascites. Cardiac arrhythmias and conduction disturbances are uncommon in chronic heartworm disease (<10%). With pulmonary parenchymal manifestations of HWD, cough and pulmonary crackles may be noted and, with granulomatosis (a rare occurrence), muffled lung sounds, dyspnea, and cyanosis are also reported. When massive pulmonary thromboembolization occurs, the additional signs of fever and hemoptysis may be noted.

Diagnosis of Canine Heartworm Disease

The Medical Management Of Heartworm Infection

Therapy of Canine Heartworm Disease

Canine Heartworm Disease: Ancillary Therapy

Canine Heartworm Disease: Complications And Specific Syndromes


The prognosis for asymptomatic heartworm infection is generally good and, although the prognosis for severe heartworm disease has to be guarded, a large percentage of such cases can be successfully managed. Once the initial crisis is past and adulticidal therapy has been successful, resolution of underlying manifestations of chronic heartworm disease begins. The prognosis is poorest with severe DIC, CS, massive embolization, eosinophilic granulomatosis, severe pulmonary artery disease, and heart failure After adulticidal therapy, intimal lesions regress rapidly. Improvement is noted as early as 4 weeks post-treatment in the main pulmonary artery, with all pulmonary arteries having undergone marked resolution within 1 year. Radiographic and arteriographic lesions of heartworm disease begin to resolve within 3 to 4 weeks, and pulmonary hypertension is reduced within months and may be normal within 6 months of adulticide therapy. Pulmonary parenchymal changes are worsened during the 6 months after adulticidal therapy and then begin to lessen in severity, with marked resolution within the next 2 to 3 months. Persistence of such lesions is suggestive of persistent infection. Corticosteroid therapy hastens the resolution of these lesions. Likewise irreversible renal disease is uncommon, with glomerular lesions resolving within months of successful adulticidal therapy. Signs of heart failure are also reversible with symptomatic therapy, cage rest, and successful clearing of infection.

Controversies In Canine Heartworm Disease

Yearlong Prevention

Macrolides As Adulticides

It is now proven that ivermectin (and possibly selamectin) has adulticidal efficacy that can approach 100% with prolonged, continuous administration. Ivermectin was demonstrated to be successful as an adulticide in experimental, young infections with 31 months’ continuous administration. The exact role of macrolides in the management of HWI, other than as preventatives, is unclear and likely to be a major controversy in upcoming years.

The appeal of macrolides for this use is that it takes the veterinarian out of the complication loop. Complications might indeed still occur but would not likely be temporally linked to the macrolide administration (as they are to arsenic use). In addition, reduced cost, patient discomfort, and inconvenience are appealing. Arguments against the use of ivermectin in this way include the following:

• Represents an off-label use of ivermectin

• Requires continuous more than 30 months’ compliance from a client that often has allowed heartworm infection to occur — often by poor compliance

• Lack of knowledge about the timing and degree of exercise restriction necessary; safe use might require 31 months of continuous exercise restriction

• Absence of a controlled kill as seen with melarsomine, reducing the ability to effectively monitor for adverse effects

• Lack of knowledge as to the effect of chronic antigen release from slowly dying adult heartworms on the kidneys and lungs

• Knowledge that macrolide “slow adulticidal therapy” does not alleviate the lung disease associated with HWI

• Fact that proven efficacy is only in young (<8 months old) experimental HWIs

• Concern that heartworm resistance to ivermectin might develop in dogs treated in this manner

At the 2001 American Heartworm Symposium, the audience and a panel of experts were polled as to their belief as to the role of ivermectin as an adulticide in their own practices. Five percent of the audience and none of the expert panelists used only ivermectin for adulticidal therapy. Approximately one third of both groups did not or would not use ivermectin as an adulticide under any circumstances. Finally, approximately 70% of the expert panel and 50% of the audience stated that they would use ivermectin for this purpose only under mitigating circumstances of financial or medical constraint.

The author recommends that melarsomine be the primary adulticidal tool and recommends or accepts the use of ivermectin in instances where a preventative is necessary in a heartworm-positive dog and the owner cannot afford arsenic therapy or in which medical conditions preclude its use; in the event of residual infection after appropriate treatment with melarsomine (assumes low worm burden); and, obviously, in unrecognized infections.


Canine Heartworm Disease: Complications And Specific Syndromes

Asymptomatic Heartworm Infection

Most dogs with heartworm infection are asymptomatic, even though many of these have heartworm disease (radiographic and pathologic lesions). Treatment is as described previously, using melarsomine in the split-dose regimen, along with a macrolide preventative.

Asymptomatic dogs may, however, become symptomatic af’er adulticidal therapy due to postadulticidal thromboembolization and lung injury (as “described elsewhere). The risk of postadulticidal thromboembolization can be imperfectly predicted by semiquantitation of the worm burden, using certain antigen tests, and by the severity of radiographic lesions. Clearly a dog with severe radiographic lesions will not tolerate thromboembolic complications well, but not all dogs with radiographic signs have heavy worm burdens. For example, a dog with moderate to severe radiographic lesions and high antigenemia may not be at high risk for postadulticidal PTE, because it is quite possible that the worms have died, explaining both the antigenemia (release from dead worms) and radio-graphic abnormalities (chronic HWD).This conclusion might also be valid in the dogs with severe radiographic lesions and negative or low antigenemia (assumes most or all worms have died, and antigen has been cleared). Alternatively, antigenic evidence of a heavy worm burden in a dog with minimal radiographic signs might still portend a severe reaction after melarsomine, because the findings suggest large worm numbers but without natural worm attrition (i.e., a relatively young infection with minimal disease). Of course, low worm burden and minimal radiographic lesions would suggest the least risk of an adverse reaction to adulticide.

It bears emphasis that with each scenario, guesswork is involved and precautions should be taken. When the risk is greatest, aspirin (5 to 7 mg/kg daily — begun 3 weeks prior to and continued until 3 weeks after adulticide) or even heparin may be used, and cage confinement is most important. The owners should be educated as to the risk, the suggestive signs, and the importance of prompt veterinary assistance in case of an adverse reaction.


The majority of dogs suffering from chronic HWI have glomerulonephritis, which can be severe. Therefore when a dog demonstrates glomerular disease, heartworm infection should be considered as a differential diagnosis. Although it is generally felt that the glomerular lesions produced by heartworm infection are unlikely to produce renal failure, a therapeutic dilemma results when one is found in a dog with proteinuria, azotemia, and HWI. Logic suggests that adulticidal therapy is indicated because heartworm infection contributes to glomerular disease, but it likewise carries risks. The approach embraced by this author is to hospitalize the patient and to administer intravenous fluids (lactated Ringer’s solution at 2 to 3 mL/kg/hr) for 48 hours (beginning 12 hours prior to the first melarsomine dose). The patient is then released, and a recheck appointment for blood urea nitrogen (BUN) and creatinine determination after 48 hours is advised. The second and third injections are tentatively scheduled for 1 to 3 months, with the treatment decision based on renal function and the overall response to initial adulticidal therapy.

Allergic Pneumonitis

Allergic pneumonitis, which is reported to affect 14% of dogs with HWD, is a relatively early development in the disease course. In fact, the pathogenesis probably involves immunologic reaction to dying microfilariae in the pulmonary capillaries. Clinical signs include cough and sometimes dyspnea and other typical signs of HWD, such as weight loss and exercise intolerance. Specific physical examination findings may be absent or may include dyspnea and audible crackles in more severe cases. Radiographic findings include those typical of heartworm disease but with an infiltrate, usually interstitial, but occasionally with an alveolar component, often worse in the caudal lung lobes. Eosinophils and basophils may be found in excess in peripheral blood and in airway samples. Corticosteroid therapy (prednisone or prednisolone at 1 to 2 mg/kg per day) results in rapid attenuation of clinical signs, with radiographic clearing in less than a week. The dose can then be stopped in 3 to 5 days if clinical signs subside. Although microfilaricidal therapy is typically not indicated because infections are often occult, macrolide prophylaxis is indicated to avoid further infection. Adulticidal therapy can be used after clinical improvement.

Eosinophilic Granulomatosis

A more serious, but rare, manifestation, pulmonary eosinophilic granulomatosis, responds less favorably. This syndrome is characterized by a more organized, nodular inflammatory process, associated with bronchial lymphadenopathy and, occasionally, pleural effusion. With pulmonary granulomatosis, cough, wheezes, and pulmonary crackles are often audible; when very severe, lung sounds may be muffled and associated with dyspnea and cyanosis. Treatment with prednisone at twice the dose for allergic pneumonitis is reported to induce partial or complete remission in 1 to 2 weeks. The prognosis remains guarded because recurrence within several weeks is common. Prednisone may be combined with cyclophosphamide or azathioprine in an effort to heighten the immunosuppressive effect. The latter combination appears to be the most effective Adulticide therapy should be delayed until remission is attained. As the prognosis for medical success is guarded; surgical excision of lobar lesions has been advocated.

Pulmonary Embolization

Spontaneous thrombosis or postadulticidal thromboembolization associated with dead and dying worms — the most important heartworm complication — may precipitate or worsen clinical signs, producing or aggravating PHT, right heart failure or, in rare instances, hemoptysis and pulmonary infarction. Acute fatalities may result from fulminant respiratory failure, exsanguination, DIC, or may be unexplained and sudden (arrhythmia or massive pulmonary embolism). The most common presentation, however, is a sudden onset of lethargy, anorexia, and cough 7 to 10 days after adulticidal therapy — often after failure to restrict exercise. Dyspnea, fever, mucous membrane pallor, and adventitial lung sounds (crackles) may be noted on physical examination. Thoracic radiographs reveal significant pulmonary infiltrates, most severe in the caudal lung lobes.

The degree of worsening, as compared with pretreatment radiographs, is typically dramatic. The infiltrate, typically alveolar, is most severe in the caudal lobes, and occasionally areas of consolidation are noted. Laboratory abnormalities vary with the severity of signs but may include leukocytosis, left shift, monocytosis, eosinophilia, and thrombocytopenia. The degree thrombocytopenia may provide prognostic information.

Medical management of thromboembolic lung disease is largely empiric and somewhat controversial. It is generally agreed that strict cage confinement, oxygen administration via oxygen cage or nasal insufflation (50 to 100 mL/kg), and prednisone (1 mg/kg/day for 3 to 7 days) are indicated in the most severe cases. KMW Some advocate careful fluid therapy (see recommendations for CS), measuring CVP to avoid precipitation of heart failure, to maximize tissue perfusion and combat dehydration. The use of heparin (75 IU/kg subcutaneously three times a day until platelet count has normalized [5 to 7 days]) and aspirin (5 to 7 mg/kg/day) has been advocated y some but remains controversial.

Other therapeutic strategies might include cough suppressants, antibiotics (if fever is unresponsive), and, although speculative at this time, vasodilators (amlodipine, hydralazine, diltiazem). If vasodilatory therapy is used, one must monitor blood pressure because hypotension is a potential side effect. Clinical improvement may be rapid and release from the hospital considered after several days’ treatment. For less severely affected dogs, careful confinement and prednisone at home are often adequate.

Congestive Heart Failure

Right heart failure results from increased right ventricular afterload (secondary to chronic pulmonary arterial disease and thromboemboli with resultant PHT). When severe and chronic, pulmonary hypertension may be complicated by secondary tricuspid regur-gitation and right heart failure. Congestive signs (ascites) are worsened in the face of hypoproteinemia. Calvert suggests that up to 50% of dogs with severe pulmonary vascular complication to heartworm disease will develop heart failure. Clinical signs variably include weight loss, exercise intolerance, ashen mucous membranes with prolonged capillary refill time, ascites, dyspnea, jugular venous distension and pulsation, arrhythmias with pulse deficits, and adventitial lung sounds (crackles and possibly wheezes). Dyspnea may be due to pulmonary infiltrates (PIE or PTE, but not cardiogenic pulmonary edema), abdominal distension, or pleural effusion.

Treatment aims include reduction of signs of congestion, reducing PHT, and increasing cardiac output. This involves dietary, pharmacologic, and procedural interventions. Moderate salt restriction is logical and probably useful in diminishing diuretic needs. This author chooses a diet designed for senior patients or early heart disease, because salt restriction should only be moderate. Diuretics may be useful in preventing recurrence of ascites but are typically not able to mobilize large fluid accumulations effectively. This then requires periodic abdominal or thoracic paracentesis (or both) when discomfort is apparent. Furosemide is typically used at 1 to 4 mg/kg daily, depending on severity and patient response Additional diuretics, which provide a supplemental effect by using differing parts of the nephron, include spironolactone (1 to 2 mg/kg orally twice a day) and chlorothiazide (2 mg/kg orally daily to every other day). The ACE-inhibitors (eg., enalapril, benazepril, lisino-pril, ramipril), by their effect on the renin-angiotensin-aldosterone system, may be of use as mixed vasodilators, in blunting pathologic cardiac remodeling, and in reducing fluid retention, particularly cases of refractory ascites. Adulticide therapy is delayed until clinical improvement is noted. No evidence indicates that digoxin improves survival in HWD. Because of the risk of toxicity and pulmonary vasoconstriction associated with its use, it is not routinely used by is author in the management of HWD-induced heart failure However, digoxin may be beneficial in the presence of supraventricular tachycardia or refractory heart failure Aspirin, theoretically useful because of its ability to ameliorate some pulmonary vascular lesions and vasoconstriction, may be used 5 mg/kg/day orally.

The arterial vasodilator, hydralazine, has been shown by Lombard to improve cardiac output in a small number of dogs with heartworm disease and heart failure. It has also been demonstrated to reduce pulmonary artery pressure and vascular resistance right ventricular work, and aortic pressure without changing cardiac output or heart rate in dogs with experimental heartworm disease (but without heart failure). Clinical experience has shown perceived improvement with the vasodilators diltiazem and amlodipine as well. Research and clinical experience suggest that hydralazine, amlodipine, and diltiazem might have a role in this setting, but further studies are necessary to define their role, if any. In heart failure the author uses hydralazine at 0.5 to 2 mg/kg orally twice a day, diltiazem at 0.5 to 1.5 mg/kg orally three times a day, or amlodipine at 0.1 to 0.25 mg/kg/day orally. The risk of hypotension with these therapies must be realized and blood pressure monitored.

Often heart failure follows adulticidal therapy, but if it is present prior to adulticidal therapy, the difficult question arises as when (or whether) to administer melarsomine. If clinical response to heart failure management is good, adulticidal therapy may be offered in 4 to 12 weeks, as conditions allow. Melarsomine is generally avoided if heart failure is refractory. Antiarrhythmic therapy is seldom necessary, although slowing the ventricular response to atrial fibrillation with digoxin, Diltiazem, or both () may be necessary in some cases.

Caval Syndrome

Heartworm CS is a relatively uncommon but severe variant or complication of HWD. Most studies have shown a marked sex predilection, with 75% to 90% of CS dogs being male. It is characterized by heavy worm burden (usually >60, with the majority of the worms residing in the right atrium and venae cavae) and a poor prognosis.

Studies performed in the author’s laboratory indicate that retrograde migration of adult heartworms to the cavae and right atrium, from 5 to 17 months after infection, produces partial inflow obstruction to the right heart and, by interfering with the valve apparatus, tricuspid insufficiency (with resultant systolic murmur, jugular pulse, and CVP increase). Affected dogs also exhibit pre-existent heartworm-induced PHT, which markedly increases the adverse hemodynamic effects of tricuspid regurgitation. These combined effects substantially reduce left ventricular preload and hence cardiac output. Cardiac arrhythmias may further compromise cardiac function.

This constellation of events precipitates a sudden onset of clinical signs, including hemolytic anemia caused by trauma to red blood cells (RBCs) as they pass through a sieve of heart-worms occupying the right atrium and venae cavae, as well as through fibrin strands in capillaries if disseminated intravascular coagulation has developed. Intravascular hemolysis, metabolic acidosis, and diminished hepatic function with impaired removal of circulating pro-coagulants contribute to the development of DIC. The effect of this traumatic insult to the erythron is magnified by increased RBC fragility, due to alterations in the RBC membrane in dogs with HWD. Hemoglobinemia, hemoglobinuria, and hepatic and renal dysfunction also are observed in many dogs. The cause of hepatorenal dysfunction is not clear, but it probably results from the combined effects of passive congestion, diminished perfusion, and the deleterious effects of the products of hemolysis. Without treatment, death frequently ensues within 24 to 72 hours due to cardiogenic shock, complicated by anemia, metabolic acidosis, and DIC.

A sudden onset of anorexia, depression, weakness, and occasionally coughing are accompanied in most dogs by dyspnea and hemoglobinuria. Hemoglobinuria has been considered pathognomonic for this syndrome. Physical examination reveals mucous membrane pallor, prolonged capillary refill time, weak pulses, jugular distension and pulsation, hepatosplenomegaly, and dyspnea. Thoracic auscultation may disclose adventitial lung sounds; a systolic heart murmur of tricuspid insufficiency (87% of cases); loud, split S2 (67%); and cardiac gallop (20%). Other reported findings include ascites (29%), jaundice (19%), and hemoptysis (6%). Body temperature varies from subnormal to mildly elevated.

Hemoglobinemia and microfilaremia are present in 85% of dogs suffering from CS. Moderate (mean PCV, 28%) regenerative anemia characterized by the presence of reticulocytes, nucleated RBC, and increased mean corpuscular volume (MCV) is seen in the majority of cases. This normochromic, macrocytic anemia has been associated with the presence of target cells, schistocytes, spur cells, and spherocytes. Leukocytosis (mean white blood cell (WBC] count, approximately 20,000 cells/cm) with neutrophilia, eosinophilia, and left shift has been described. Dogs affected with disseminated intravascular coagulation are characterized by the presence of thrombocytopenia and hypofibrinoginemia, as well as prolonged one stage prothrombin time (PT), partial thromboplastin time (PTT), activated coagulation time (ACT), and high fibrin degradation product concentrations. Serum chemistry analysis reveals increases in liver enzymes, bilirubin, and indices of renal function. Urine analysis reveals high bilirubin and protein concentrations in 50% of cases and more frequently, hemoglobinuria.

CVP is high in 80% to 90% of cases (mean, 11.4 cm H20). Electrocardiographic abnormalities include sinus tachycardia in 33% of cases and atrial and ventricular premature complexes in 28% and 6%, respectively. The mean electrical axis tends to rotate rightward (mean, +129 degrees), with an S1,2,3 pattern evident in 38% of cases. The S wave depth in CV6LU (V<) is the most reliable indicator of right ventricular enlargement (>0.8 mv) in 56% of cases. Thoracic radiography reveals signs of severe heartworm disease with cardiomegaly, main pulmonary arterial enlargement, increased pulmonary vascularity, and pulmonary arterial tortuousity recognized in descending order of frequency (). Massive worm inhabitation of the right atrium with movement into the right ventricle during diastole is evident echocardiographically. This finding on M-mode and two-dimensional echocardiograms is nearly pathognomonic for CS in the appropriate clinical setting. The right ventricular lumen is enlarged and the left diminished in size, suggesting pulmonary hypertension accompanied by reduced left ventricular loading. Paradoxical septal motion, caused by high right ventricular pressure, is commonly observed. No echocardiographic evidence of left ventricular dysfunction exists. Cardiac catheterization documents pulmonary, right atrial, and right ventricular hypertension and reduced cardiac output.

Prognosis is poor unless the cause of the crisis — the right atrial and caval heartworms — is removed. Even with this treatment, mortality can approximate 40%.

Fluid therapy is needed to improve cardiac output and tissue perfusion, to prevent or help to reverse DIC, to prevent hemoglobin nephropathy, and to aid in the correction of metabolic acidosis. Overexuberant fluid therapy, however, may worsen or precipitate signs of congestive heart failure. In the author’s clinic, a left jugular catheter is placed and intravenous fluid therapy instituted with 5% dextrose in water or one-half strength saline and 2.5% dextrose. The catheter should not enter the anterior vena cava because it will interfere with worm embolectomy. A cephalic catheter may be substituted for the somewhat inconvenient jugular catheter, but this does not allow monitoring of CVP. The intravenous infusion rate for fluids is dependent on the condition of the animal. A useful guideline is to infuse as rapidly as possible (up to 1 cardiovascular volume during the first hour) without raising the CVP or without raising it above 10 cm H20 if it was normal or near normal at the outset. Initial therapy should be aggressive (10 to 20 mL/kg/hr for the first hour) if shock is accompanied by a normal CVP (<5 cm HzO), and it should be curtailed to approximately 1 to 2 mL/kg/hr if CVP is 10 to 20 cm HzO. Whole blood transfusion is not indicated in most cases because anemia usually is not severe, and transfused coagulation factors may worsen DIG Sodium bicarbonate is not indicated unless metabolic acidosis is severe (pH, 7.15 to 7.20). Broad-spectrum antibiotics and aspirin (5 mg/kg daily) should be administered. Treatment for disseminated intravascular coagulation is described elsewhere in this text.

The technique for surgical removal of caval and atria] heartworms was developed by Jackson and colleagues. This procedure should be undertaken as early in the course of therapy as is practical. Often, sedation is unnecessary, and the procedure can be accomplished with only local anesthesia. The dog is restrained in left lateral recumbency after surgical clipping and preparation. The jugular vein is isolated distally. A ligature is placed loosely around the cranial aspect of the vein until it is incised, after which the ligature is tied. Alligator forceps (20 to 40 cm, preferably of small diameter) are guided gently down the vein while being held loosely between the thumb and forefinger. The jugular vein can be temporarily occluded with umbilical tape. If difficulty is encountered in passage of the forceps, gentle manipulation of the dog by assistants to further extend the neck will assist in passage of the forceps past the thoracic inlet; medial direction of the forceps may be necessary at the base of the heart. Once the forceps have been placed, the jaws are opened, the forceps are advanced slightly, the jaws are closed, and the worms are removed. One to four worms are usually removed with each pass. This process is repeated until five to six successive attempts are unsuccessful. An effort should be made to remove 35 to 50 worms. Care should be taken not to fracture heartworm during extraction. After worm removal, the jugular vein is ligated distally, and subcutaneous and skin sutures are placed routinely. Other catheters, such as urethral stone basket catheters, horsehair brushes, snares and flexible alligator forceps have also been used. Fluoroscopic guidance, when available, is useful in this procedure.

Successful worm retrieval is associated with a reduction in the intensity of the cardiac murmur and jugular pulsations, rapid clearing of hemoglobinemia and hemoglobinuria, and normalization of serum enzymatic aberrations. Immediate and latent improvement in cardiac function occurs over the next 24 hours. It is important to realize that removal of worms does nothing to reduce right ventricular afterload (PHT), and hence fluid therapy must be monitored carefully before and after surgery to avoid precipitation or worsening of right heart failure. Cage rest should be enforced for a period of time suitable for individual care.

Worm embolectomy through a jugular venotomy is frequently successful in stabilizing the animal, allowing adulticide therapy to be instituted to destroy remaining heartworms in a minimum of 1 month. Careful scrutiny of BUN and serum liver enzyme concentrations should precede the latter treatment. Aspirin therapy is continued for 3 to 4 weeks after adulticide therapy. Substantial improvement in anemia should not be expected for 2 to 4 weeks after worm embolectomy. Macrolide preventative therapy, as described previously, is administered at the time of release from the hospital.

Aberrant Migration

Although heartworms in the dog typically inhabit the pulmonary arteries of the caudal lung lobes, they may find their way to the right ventricle, and rarely (see Caval Syndrome) the right atria and venae cavae. Much less frequently, immature L5 may aberrantly migrate to other sites, including the brain, spinal cord, epidural space, anterior chamber of the eye, the vitreous, the subcutis, and the peritoneal cavity. In addition, the worms may inhabit the systemic circulation, producing systemic thromboembolic disease. Treatment of aberrantly migrating heartworms requires either nothing (e.g., peritoneal cavity), surgical excision of the offending parasite, adulticidal therapy, or symptomatic treatment (e.g., seizure control with brain migration). The method for surgical removal from internal iliac and femoral arteries has been described.


Dilated Cardiomyopathy: Acute Therapy

Treatment Goals

The treatment goals depend on the type and severity of the clinical signs. If severely dyspneic the initial goal is to make it easier for the cat to breathe by removing pleural effusion, by reducing pulmonary edema pharmacologically, or by administering oxygen. If the primary problem is a marked reduction in perfusion leading to hypothermia, the goal is to increase cardiac output, if possible, via the administration of an intravenous positive inotropic agent, such as dobutamine, and possibly the judicious use of intravenous fluid administration, especially if the cat is severely dehydrated.


Pleurocentesis is often life saving in the severely dyspneic cat that has a large amount of pleural effusion. Thoracocentesis is described in posts.

Diuretic Therapy

Diuretic administration is the only reliable way to reduce pulmonary edema formation in a cat with severe dilated cardiomyopathy. Furosemide is used almost exclusively. The dose depends on the severity of the pulmonary edema, on whether the cat is currendy on furosemide for heart failure, and whether the situation is acute or chronic Cats in severe respiratory distress may need an initial dose as high as 2 mg/lb parenterally. Intravenous administration is preferred, but the drug should be administered intramuscularly if restraint for intravenous administration produces stress. Absorption half-life after intramuscular administration is around 5 minutes, so the entire dose is fully absorbed within 20 to 25 minutes. The duration of effect of furosemide after parenteral administration is probably 1 to 2 hours in a cat in heart failure. Consequently, another dose should be administered within that period if the cat is still in respiratory distress and is not severely dehydrated. A cat with a lesser amount of pulmonary edema and less respiratory distress needs a smaller dose of furosemide parenterally in the acute setting. Respiratory rate and character should be monitored carefully after diuretic administration with the cat in an oxygen-enriched environment.


Increasing the percent concentration of oxygen delivered to the alveoli is critical in cats in respiratory distress. This can be accomplished using a face mask, standard oxygen cage, a pediatric incubator, or nasal insufflation. Generally the goal is to increase fraction of inspired oxygen (FIO2) to at least 40% (normal is 21%). If the cat resists a face mask, it should not be used. When placed in a confined space, especially a small space like an incubator, it is mandatory to keep the environmental temperature and the carbon dioxide concentration within reasonable levels. Failure to do so can cause death. A canister containing sodium lime or barium hydroxide lime controls carbon dioxide level in an oxygen cage, and a refrigeration unit controls temperature. Carbon dioxide concentration is usually controlled in an incubator by maximizing the flow rate of oxygen (and therefore flushing out the carbon dioxide).

Inotropic Support

Beta-adrenergic agonists, usually dobutamine or dopamine, can be used for acute inotropic support in a cat widi severe dilated cardiomyopathy and severe heart failure. However, conscious cats have more side effects with these drugs than do dogs. They often appear agitated and may even seizure. The half-life of these drugs is around 1 minute, so stopping the drug infusion results in rapid cessation of adverse effects. The infusion rate for dobutamine and dopamine in a cat is less than that used in a dog and is generally in the range of 1 to 2.5 Mg/lb/min.


Nitroprusside is a potent dilator (i.e., smooth muscle relaxant) of systemic arterioles and systemic veins. It can only be used in cats with dilated cardiomyopathy that are not in cardiogenic shock (systolic systemic arterial blood pressure over 100 mm Hg). If systemic pressure is adequate, the drug can be used in one of two ways: (1) empirically at a dose of 2 µg/lb/min or (2) titrated using blood pressure starting at a dose of 1 ug/lb/min and increased until the systolic pressure has decreased by at least 10 to 15 mm Hg. ()

General Supportive Measures

Although dogs commonly start to drink water and eat once they are no longer in respiratory distress, cats may not. Dehydration is a common side effect of aggressive diuretic therapy, and some cats are dehydrated at presentation. Generally cats do better if they are sent home as soon as possible. However, if hospitalization is required after the edema and effusion are controlled, judicious use of fluid therapy may be needed. Electrolyte disturbances, most commonly hyponatremia, hypokalemia, and hypochloremia, are also more frequent in cats than in dogs in this acute setting. Consequendy, serum electrolyte concentrations should be monitored.


Dilated Cardiomyopathy: Chronic Therapy

Diuretic Therapy

Diuretics are the only drugs that can routinely control the clinical signs referable to congestion and edema due to heart failure. Consequently, it is mandatory for cats with congestive heart failure to be on a diuretic, usually furosemide. The chronic orally administered dose for furosemide in cats is wide and ranges from 0.5 mg/lb a day to 2 mg/lb every 8 hours. The most common doses are 6.25 to 12.5 mg per cat every 8 to 12 hours, orally. In general, cats need a lower dose of furosemide when compared with dogs, although the upper end of the dose range can be similar. The goal of diuretic therapy is to keep pulmonary edema and pleural effusion controlled. This should be done with the lowest possible furosemide dose, although in the author’s experience, underdosing appears to be a more frequent problem than does overdosing. Every owner should be instructed to count his or her cat’s respiratory rate at home when the cat is sleeping or resting quiedy in a cool environment and to keep a written log. The normal respiratory rate for a cat is in the 20 to 40 breaths per minute range. If the rate is greater than 40 breaths per minute or the owner notes that the character of breathing is more labored, these are signals that an increased dose of furosemide, pleurocentesis, or both are needed. Changes in furosemide dose should be done in consultation with a veterinarian during the initial stages of management. Some owners will require continued contact with a veterinarian to manage dose changes, whereas others will reach a point where they feel comfortable doing this on their own. Cats with severe disease that require a maximum dose of furosemide are often mildly to moderately dehydrated and mildly to moderately azotemic. As long as they continue to eat, drink, and appear comfortable, the dose of furosemide should not be decreased. If the dehydration or azotemia becomes severe enough to cause anorexia, the furosemide administration must be discontinued as long as the cat is not taking in fluid. Owners must be warned that continued use of high-dose furosemide administration in a cat that is not drinking or eating can result in severe, life-threatening dehydration. Judicious use of parenteral fluid administration may be required. These, of course, are poor prognostic signs. Cats that are refractory to the maximum dose of furosemide may need to have another diuretic administered along with the same maximum dose of furosemide. Choices include a thiazide diuretic and possibly spironolactone. () Parenteral administration of furosemide may also be beneficial because the oral bioavailability of the drug is only around 50%.


Repeated pleurocentesis is often required in cats with pleural effusion. Pleurocentesis may need to be done as infrequently as once a month or as frequendy as every 4 or 5 days. As much fluid as possible should be removed at each visit. Ultrasound guidance often helps identify regions where fluid has pocketed. Chylothorax secondary to heart failure can result in chylofibrosis, making it very difficult to remove as much fluid as one would like. Risks of repeated pleurocentesis include infection, pneumothorax, and bleeding, but all are rare.

Angiotensin-Converting Enzyme Inhibitors

Any cat with idiopathic dilated cardiomyopathy should be on an angiotensin-converting enzyme (ACE) inhibitor for long-term management unless they have an adverse reaction to the drug. Enalapril is most commonly used at a dose of 1.25 to 2.5 mg per cat orally every 24 hours. angiotensin-converting enzyme inhibitors can almost never be used on their own to control signs of heart failure and are not effective for controlling heart failure in the acute care setting. Rather they must be administered in concert with a diuretic and help in the long-term control of the disease. Generally, angiotensin-converting enzyme inhibitor therapy should be started when the cat is reasonably stable and not dehydrated.


Digoxin, in theory, may be administered to cats with dilated cardiomyopathy. However, in the initial trial that identified taurine deficiency as a cause of feline dilated cardiomyopathy, digoxin was not administered and most of those cats survived; therefore clearly in cats with dilated cardiomyopathy due to taurine deficiency, no clear mandate exists to administer digoxin.

Dietary Modifications

Any cat with dilated cardiomyopathy should be supplemented with 250 mg taurine orally every 12 hours until the results of the plasma and whole blood taurine concentration analysis are evaluated. Taurine is inexpensive and can be purchased from health food stores or chemical supply houses. Cats that are taurine deficient should be continued on taurine supplementation, whereas those that are not may be taken off or left on at the discretion of the owner. Sodium-restricted diets may be useful, particularly in cats that are refractory to drug therapy. However, it is more important to keep the cat eating than it is to force sodium restriction.


HCM: Pathophysiology

Hypertrophy, Diastolic Dysfunction, and Congestive Heart Failure

Enlarged papillary muscles and a thick left ventricular myocardium with a normal to small left ventricular chamber characterize hypertrophic cardiomyopathy. hypertrophic cardiomyopathy may be mild, moderate, or severe. Severe concentric hypertrophy by itself increases chamber stiffness. In addition, blood flow and especially blood flow reserve to severely thickened myocardium is compromised, which causes myocardial ischemia, cell death, and replacement fibrosis. This has been documented in cats by showing that cardiac troponin I concentration, a protein released into the systemic circulation after cell necrosis, is increased in cats with severe hypertrophic cardiomyopathy. Increased concentrations of circulating neurohormones may also stimulate interstitial fibrosis. Fibrosis increases chamber stiffness (increased pressure for any given volume) further and is probably the primary reason for the marked diastolic dysfunction seen in this disease. The stiff ventricular chamber causes a greater increase in pressure for any given increase in volume when the ventricle fills in diastole. This produces congestive heart failure (i.e., pulmonary edema and pleural effusion).The myocardium from cats with hypertrophic cardiomyopathy also takes a longer time to relax in early diastole, although the clinical significance of this is unknown. When left ventricular hypertrophy is severe, it is common for the left ventricular wall thickness to be twice the normal thickness. Consequently, left ventricular wall thickness is commonly in the 7 to 10 mm range when hypertrophic cardiomyopathy is severe in cats. This severe concentric hypertrophy may encroach on the left ventricular cavity in diastole, decreasing its size, although left ventricular diastolic diameter is commonly within the normal range. The end-systolic volume and diameter are almost always reduced, often to zero (endsystolic cavity obliteration). Global myocardial contractility is normal in humans with hypertrophic cardiomyopathy, and die reduction in end-systolic volume is due to a decrease in afterload (wall stress) brought on by the increase in wall thickness.

Systolic Anterior Motion of the Mitral Valve A phenomenon called systolic anterior motion (SAM) of the mitral valve is common in cats with hypertrophic cardiomyopathy ().

Cats with hypertrophic cardiomyopathy and systolic anterior motion are commonly said to have the obstructive type of hypertrophic cardiomyopathy or hypertrophic obstructive cardiomyopathy (HOCM). In one survey of 46 cats, systolic anterior motion was present in 67%. systolic anterior motion of the mitral valve is the process of the septal (anterior] mitral valve leaflet or the chordal structures inserting on this leaflet being pulled into the left ventricular outflow tract during systole. Here it is caught in the blood flow and pushed toward (and often ultimately against) the IVS. The initial pulling of the mitral valve leaflet toward the left ventricular outflow tract in systole can clearly be seen on many echocardiograms from cats with hypertrophic cardiomyopathy. The grossly enlarged papillary muscles encroach on the left ventricular outflow tract (the region of the left ventricular between the anterior leaflet of the mitral valve and the IVS in diastole) and pull the mitral apparatus structures into the basilar region of the outflow tract. This situation has been reproduced experimentally in dogs by surgically displacing the papillary muscles cranially. systolic anterior motion of the mitral valve produces a dynamic subaor-tic stenosis that increases systolic intraventricular pressure in mid- to late systole. The dynamic subaortic stenosis increases the velocity of blood flow through the subaortic region and often produces turbulence. Simultaneously, when the septal leaflet is pulled toward the IVS, this produces a gap in the mitral valve, creating mitral regurgitation. These abnormalities are by far the most common cause of the heart murmur heard in cats with hypertrophic cardiomyopathy. The process of systolic anterior motion is dynamic — worsening when contractility increases and lessening when contractility decreases. This also makes the murmur dynamic — increasing in intensity with increasing excitement and softening when the cat becomes calmer.

Pleural Effusion Along with pulmonary edema, pleural effusion is common in cats with heart failure. It can be a modified transudate, pseudochylous or true chylous in nature. The most common cause of chylothorax in cats is heart failure. It is unknown exactly why pleural effusion develops in these cats. Two possibilities exist: The first is that left heart failure results in pulmonary hypertension severe enough to cause right heart failure. This does not appear to occur very frequently in cats because it is unusual to identify echocardiographic right heart enlargement, jugular and hepatic vein distension, or ascites in these cases. The second possibility is that feline visceral pleural veins drain into the pulmonary veins such that elevated pulmonary vein pressure (congestive left heart failure) causes the formation of pleural effusion. In the dog the visceral pleura is supplied by pulmonary arteries and drained by pulmonary veins. The dog, the cat, and the monkey have type II lungs.w One characteristic of type II lungs is that the visceral pleura is supplied not by bronchial arteries but by pulmonary arteries.

Presumably this means that the cat visceral pleura is also drained by pulmonary veins. This means that pulmonary venous hypertension secondary to left heart failure could cause pleural effusion in cats as it does in humans.

Pathology of hypertrophic cardiomyopathy

Gross Pathology Cats with severe hypertrophic cardiomyopathy have severe thickening of the left ventricular myocardium (the IVS and free wall), with the left ventricular wall commonly being 7 to 10 mm thick (). The hypertrophy may be symmetrical, involving the entire circumference of the LV, but it may also be asymmetrical. In some cats the IVS is significandy thicker than the free wall, whereas in others the free wall is thicker (asymmetrical hypertrophy). In those cats with primarily septa] hypertrophy, the hypertrophy may be confined to the basilar region of the septum, and in others may be apical. Isolated free wall hypertrophy most commonly occurs in the region between the papillary muscles. As in many pathologic specimens, hearts from cats with hypertrophic cardiomyopathy may undergo contraction (rigor) after death, resulting in a wall thickness that is closer to the end-systolic wall thickness in life rather than the end-diastolic thickness. Consequently, heart weight must be combined with subjective or objective evidence of left ventricular wall thickening to make the diagnosis of hypertrophic cardiomyopathy postmortem. To weigh a cat heart the pericardium should be removed and the aorta and pulmonary artery transected so that no more than 2 to 4 cm are left. Normal heart weight-to-body weight ratio has been reported to be 10.6 +/- 4 g/lb, with cats with hypertrophic cardiomyopathy having a ratio of 13.2 +/-3.1 g/1b. This results in a large overlap between the two groups. In the author’s experience, most normal-sized cats (6 to 12 lb) have a heart that weighs less than 20 g and most cats in this size range with hypertrophic cardiomyopathy have a heart that weighs more than 20 g. Cats with severe hypertrophic cardiomyopathy almost always have a heart that weighs more than 25 g, usually over 30 g, and can be as heavy as 38 g.

The left atrium is often enlarged in cats with severe hypertrophic cardiomyopathy, often markedly so. However, with early, severe disease, the author has identified normal left atrial size in some Maine coon cats. Occasionally a thrombus is present in the body of the left atrium or within the left auricle.

Cats with milder forms of the disease (mild to moderate hypertrophic cardiomyopathy) have lesser wall thickening and a more normal-sized left ventricular chamber. The left atrium may be normal in size or may be enlarged. Papillary muscle hypertrophy may be the predominant lesion.

Histopathology Histopathologically, a wide range of abnormalities exist. In some hearts, only myocyte hypertrophy is evident. On the other end of the spectrum, some cats have moderate to severe interstitial and replacement fibrosis and dystrophic mineralization (20% to 40% of cases). Intramural coronary arteriosclerosis is present in approximately 75% of cats with hypertrophic cardiomyopathy. Intramyocardial small artery disease is not specific for hypertrophic cardiomyopathy because it is also identified in cats and dogs with many cardiac diseases.

In humans, myocardial fiber disarray that involves at least 5% of the myocardium in the IVS is found in 90% of patients with familial hypertrophic cardiomyopathy. Other diseases that produce concentric hypertrophy can also cause myocardial fiber disarray, but this almost always involves less than 1% of the myocardium. In cats with hypertrophic cardiomyopathy, myocardial fiber disarray in the IVS of the same magnitude observed in humans is only identified in 30% to 60% of cases.’ However, myocardial fiber disarray is a consistent feature of hypertrophic cardiomyopathy in Maine coon cats. Sarcomeres also have disarray in human patients with hypertrophic cardiomyopathy. Interestingly, infecting isolated feline cardiocytes with an adenoviral vector containing a full-length mutated human β-myosin heavy chain gene causes sarcomere disruption.

Natural History and Prognosis

The prognosis, as with most cardiac diseases, is highly variable for hypertrophic cardiomyopathy. Some of it is determined by clinical presentation and echocardiographic severity of the disease. Adult cats that are asymptomatic and have mild to moderate disease and no to mild left atrial enlargement have a good short-term (and possibly a good long-term) prognosis. Some, however, may progress to more severe disease and some may die suddenly. Asymptomatic cats with severe wall thickening and mild to moderate left atrial enlargement have a guarded prognosis for developing heart failure in the future. They probably have some risk for developing thromboembolism and may be at risk for sudden death. Cats with no clinical signs but with severe wall thickening and moderate to severe left atrial enlargement are at risk for developing heart failure or often already have mild to moderate heart failure that has gone undetected. These cats are at risk for developing systemic thromboembolic disease and sudden death, although both of these risks appear to be relatively small. Cats presented in heart failure usually have a poor prognosis, but survival time is highly variable. Most die of intractable heart failure. Some develop thromboembolism, and some die suddenly. In one study a MST of 3 months was reported yet some cats (about 20% in one study) in this class stabilize and do well for prolonged periods. The author and colleagues have seen some cats with severe hypertrophic cardiomyopathy live as long as 2.5 years after the diagnosis of heart failure. Some of these cats may develop heart failure when they are stressed and become severely tachycardic and then stabilize after that time. Cats with severe hypertrophic cardiomyopathy and aortic thromboembolism in the aforementioned study had a very poor prognosis with a MST of 2 months.

Hypertrophic Cardiomyopathy: Clinical Manifestations

Differential Diagnoses

Hyperthyroidism and systemic hypertension need to be ruled out as either primary or complicating factors. Hyperthyroidism is usually easy to rule out. Devices to measure blood pressure in the cat, however, are not always readily available, and the technique requires some practice to acquire accurate values. In addition, systolic systemic arterial blood pressure may be increased in a normal cat that is stressed, so repeat measurements of increased blood pressure are preferred before a diagnosis of systemic hypertension is made If systemic arterial blood pressure cannot be measured, one should at least rule out the common causes of systemic hypertension in a cat with left ventricular concentric hypertrophy (i.e., hyperthyroidism, renal failure).

Rarely, infiltrative disease such as lymphoma will produce hypertrophy that is indistinguishable from hypertrophic cardiomyopathy on an echocar-diogram. One such case has been reported. Cats that are homozygous for the dystrophin deficiency seen in hypertrophic feline muscular dystrophy also have thickened but hypoechoic myocardium with hyperechoic foci in the left ventricular myocardium and papillary muscles. The myocardium contains foci of mineralization and no dystrophin.

Precipitating Factors

Certain factors may precipitate heart failure or sudden death in a cat with hypertrophic cardiomyopathy. Stress (cat fight), anesthesia (especially with ketamine), and surgery appear to be factors. The administration of a long-acting corticosteroid also appears to be a factor that either produces or worsens heart failure in cats, presumably through the mineralocorticoid effects of these drugs.

Therapy of Cats with No Clinical Signs

No evidence exists to show that any drug alters the natural history of hypertrophic cardiomyopathy in domestic cats until they are in heart failure. Diltiazem, atenolol, or enalapril are commonly administered to cats with mild to severe hypertrophic cardiomyopathy that are not in heart failure on an empiric basis. Whenever hypertrophic cardiomyopathy is diagnosed in a cat, the veterinarian should explain the situation to owners and try to let them make informed decisions based on their wishes and life styles. Because no intervention is known to change the course of the disease, treatment at this stage is not mandated.

Treatment Goals and General Therapy of Cats in Heart Failure

Cats that present in heart failure have clinical signs referable to pulmonary edema, pleural effusion, or both. Consequendy, therapy is generally aimed at decreasing left atrial and pulmonary venous pressures in these cats and physically removing the effusion. In some cats with severe heart failure, clinical evidence of hypoperfusion (low-output heart failure) may be apparent in addition to the signs of congestive heart failure. The signs may be manifested primarily as cold extremities.

Pulmonary edema is primarily treated with diuretics (almost exclusively with furosemide) acutely and chronically and an angiotensin-converting enzyme enzyme inhibitor chronically, although recent evidence suggests that angiotensin-converting enzyme inhibition may not be that helpful in prolonging survival in cats with hypertrophic cardiomyopathy. Diltiazem and beta-adrenergic blockers, usually atenolol, have been commonly used as adjunctive agents. Recent evidence suggests that diltiazem is not helpful in prolonging survival in cats with heart failure due to severe hypertrophic cardiomyopathy and that atenolol may actually shorten survival time. Plcurocentesis is most effective for treating cats with severe pleural effusion. Furosemide is helpful for preventing or slowing recurrent effusion.

Hypertrophic Cardiomyopathy: Acute Therapy

Hypertrophic Cardiomyopathy: Chronic Therapy

Refractory Heart Failure

Heart failure that is refractory to furosemide and an angiotensin-converting enzyme inhibitor portends a poor prognosis. Another diuretic may be added to the therapeutic regimen. A thiazide diuretic is generally the mast rewarding but is also more likely to cause complications, such as dehydration and electrolyte (sodium, potassium, chloride, magnesium) depletion. Spironolactone, in theory, may have some beneficial effects related to blocking aldos-terone’s actions; however, clinically it rarely results in noticeable improvement, and its efficacy is unproven. A low sodium diet may be helpful, if palatable. This diet can be a commercial one or one that is devised by a nutritional service. Home-cooked diets formulated by the owner are discouraged unless the owner is counseled. If severe systolic anterior motion is present and atenolol is not already part of the therapeutic regimen, it may be added at this stage.


Hypertrophic Cardiomyopathy: Acute Therapy

Just as with dilated cardiomyopathy, cats that have respiratory distress suspected of having heart failure secondary to hypertrophic cardiomyopathy may need to be placed in an oxygen-enriched environment as soon as possible. If possible the cat should be initially evaluated by doing a cursory physical examination, taking care not to stress the patient during this or any other procedure, because stress exacerbates dyspnea and arrhythmias and often leads to death. Most, but not all, cats with severe hypertrophic cardiomyopathy that are in heart failure will have a heart murmur and gallop rhythm. A butterfly catheter should be used to perform thoracentesis on both sides of the chest to look for pleural effusion as soon as possible. Generally this should be done with the cat in a sternal position so that it does not become stressed during the procedure. Clipping of the hair is not needed. If fluid is identified, it should be removed. Most cats that arc dyspneic due to pleural effusion have 150 to 250 mL of fluid in their pleural space. If none is identified, a lateral thoracic radiograph to identify pulmonary edema may be taken with the veterinarian present to ensure that the cat is not stressed (e.g., the clinician should make sure no one stretches the cat out or in any way interferes with its ability to breathe). If the patient struggles or appears to be stressed or fractious during or before radiographic examination, the procedure should be canceled and the patient placed into an oxygen-enriched environment. A preferable alternative to blind tapping is to perform a superficial ultrasonographic examination to identify and locate fluid accumulation.


Furosemide should initially be administered intravenously or intramuscularly to the cat in severe respiratory distress. The route of administration depends on the stress level of the patient. Furosemide should bo administered intramuscularly to cats that are very distressed and cannot tolerate restraint for an intravenous injection. Cats that can tolerate an intravenous injection may benefit from the more rapid onset of action (within 5 minutes of an intravenous injection versus 30 minutes for an intramuscular injection).The initial rurosemide dose to a cat in distress should generally be in the 1 to 2 mg/lb range, intramuscularly or intravenously. This dose may be repeated within 1 hour to 2 hours ().

High-dose parenteral furosemide therapy commonly produces electrolyte disturbances and dehydration in cats. Cats with severe heart failure that require intensive therapy are often precarious. They may be presented dehydrated and electrolyte-depleted because of anorexia. They may remain anorexic and consequently dehydrated and depleted of electrolytes once the edema, the effusion, or both are lessened. Judicious intravenous or subcutaneous fluid administration may be required to improve these cats clinically. Overzealous fluid administration will result in the return of congestive heart failure. If fluid administration is required, the furosemide administration must be discontinued for that time.


Anecdotally, nitroprusside may be beneficial in cats with severe pulmonary edema due to hypertrophic cardiomyopathy. As with dilated cardiomyopathy, it may be administered empirically at 2 ug/lb/min or titrated, using blood pressure measurement to document efficacy, starting at a dose of 1 to 2 pg/lb/min. Nitroprusside has a very short half-life. Consequently, if clinically significant systemic-hypotension is produced (e.g., weakness, collapse, poor capillary refill time) cessation of the infusion will result in the systemic blood pressure returning to normal within several minutes.


Nitroglycerin cream may be beneficial in cats with severe edema formation secondary to feline cardiomy-opathy. However, no studies have examined effects or efficacy. Nitroglycerin is safe and some benefit may occur with its administration in some cats. Consequently, one-eighth inch to one-fourth inch of a 2% cream may be administered to the inside of an ear every 4 to 6 hours for the first 24 hours as long as furosemide is being administered concomitandy. Nitroglycerin is not a primary drug. Tolerance develops rapidly in other species, and prolonged administration is probably of even lesser benefit.

Once drug administration is complete, the cat should be left to rest quietly in an oxygen-enriched environment. Care should be taken not to distress the cat. A baseline measurement of the respiratory rate and assessment of respiratory character should be taken when the cat is resting. This should be followed at 30-minute intervals and furosemide administration continued until the respiratory rate starts to decrease (a consistent decrease of the respiratory rate from 70 to 90 breaths per minute into the 50 to 60 breaths per minute range is a general guide), the character of the cat’s respiratory effort improves, or both occur. When this happens, the furosemide dose and dose frequency should be curtailed sharply.

Sedation or Anesthesia

In some cats, sedation with acepromazine (0.02 to 0.5 mg/lb intramuscularly or intravenously) may help by producing anxiolysis. Oxymorphone (0.02 to 0.04 mg/lb every 6 hours intramuscularly, intravenously, or sub-cutaneously) or butorphanol tartrate (0.04 mg/lb intravenously or 0.18 mg/lb every 4 hours subcutaneously) may also be used but are secondary choices because they can produce respiratory depression. Oxymorphone may produce excitement in some cats.

In some cats with fulminant heart failure, anesthesia, intubation, and ventilation are required to control the respiratory failure. Although this method is not preferred for most severely dyspneic cats, it can be life saving in some. This procedure has the advantage of being able to administer 100% oxygen and to be able to drain or suction fluid from the large airways in a controlled environment. The disadvantage is the administration of anesthetic agents to a cat that has cardiovascular compromise.


Hypertrophic Cardiomyopathy: Chronic Therapy

Many aspects of chronic therapy of hypertrophic cardiomyopathy are controversial. All therapy is palliative. Furosemide is the only drug that has a clearly beneficial effect chronically on survival in cats with hypertrophic cardiomyopathy.


Many cats with hypertrophic cardiomyopathy are dyspneic because of pleural effusion that reaccumulates despite appropriate medical therapy. These cats need periodic pleurocentesis ().


In cats with congestive heart failure due to hypertrophic cardiomyopathy, rurosemide administration, once initiated, should usually be maintained for the rest of the cat’s life. In a few cases, furosemide can be discontinued gradually once the cat has been stabilized. This usually only occurs in a cat that has had a precipitating stressful event.

As for dilated cardiomyopathy, the maintenance dose of furosemide in cats usually ranges from 6.25 (one half of a 12.5 mg tablet) once a day to 12.5 mg orally every 8 hours, although the dose may be increased further if the cat is not responding to a conventional dose. The author and colleagues have administered higher doses (up to 37.5 mg every 12 hours) than commonly recommended to a few cats with severe heart failure without identifying severe consequences as long as the cats were eating and drinking. Cats on high-dose furosemide therapy are commonly mildly dehydrated and mildly to moderately azotemic. However, they often continue to maintain a reasonable quality of life.

The furosemide dose needs to be titrated carefully in each patient. The owner should be taught how to count the resting respiratory rate at home and instructed to keep a daily written log of the respiratory rate as oudined previously under dilated cardiomyopathy. This is highly beneficial for making decisions regarding dose adjustment in individual patients.

Angiolensin-Converting Enzyme Inhibitors

Although furosemide has been used to treat heart fadure secondary to feline hypertrophic cardiomyopathy for decades, the use of angiotensin-converting enzyme inhibitors in cats with hypertrophic cardiomyopathy is relatively recent, because veterinarians, like their colleagues who treat humans, feared that the use of angiotensin-converting enzyme inhibitors would worsen systolic anterior motion in their patients. Over the past 10 years it has become obvious to most veterinary cardiologists that angiotensin-converting enzyme inhibitors do not worsen the clinical signs referable to hypertrophic cardiomyopathy, and a recent study has documented that systolic anterior motion is not worsened by enalapril administration in cats. Many have believed and one study has suggested that angiotensin-converting enzyme inhibitors improve the quality and quantity of life of cats with hypertrophic cardiomyopathy. Preliminary evidence from a recent placebo-controlled and blinded clinical trial suggests that enalapril produces little to no benefit when compared with furosemide alone in cats with heart failure due to hypertrophic cardiomyopathy. However, this study also included cats with unclassified (restrictive) cardiomyopathy and both cats with and without SAM. Subgroup analysis failed to change the conclusions of the study but die subgroups were small. Consequendy, it is the recommendation of this author to continue to use an angiotensin-converting enzyme inhibitor in cats in heart failure due to hypertrophic cardiomyopathy at a dose of 1.25 to 2.5 mg orally every 24 hours.


In cats with severe hypertrophic cardiomyopathy that have or have had evidence of CHF, diltiazem or a beta-adrenergic blocking agent are often administered. Both provide symptomatic benefit in human patients. Their use in cats with hypertrophic cardiomyopathy is controversial; however, little doubt exists that neither drugs produces dramatic benefits. Diltiazem, however, appears to produce no harm.M

Diltiazem is a calcium channel blocker previously reported to produce beneficial effects in cats with hypertrophic cardiomyopathy when dosed at 7.5 mg every 8 hours. Beneficial effects that have been reported include lessened edema formation and decreased wall thickness in some cats. In the author’s experience only a few cats appear to experience a clinically significant decrease in wall thickness, and it is impossible to tell ii this is due to drug effect or time. Rarely does it appear clinically that diltiazem controls congestive heart failure on its own or helps control pulmonary edema or pleural effusion when added on to furosemide therapy. Diltiazem does improve the early diastolic relaxation abnormalities seen in feline hypertrophic cardiomyopathy. Whether this helps decrease diastolic intraventricular pressure and so decrease edema formation is unknown. Theoretically it should have little benefit in the resting cat with a slow heart rate. Slower myocardial relaxation during rapid heart rates may not allow the myocardium enough time to relax, resulting in increased diastolic intraventricular pressure. Diltiazem may help protect a cat that undergoes a stressful event. Incomplete relaxation and decreased compliance, however, are more plausible explanations for increased diastolic pressure due to diastolic dysfunction in feline hypertrophic cardiomyopathy. In humans, diltiazem does not change left ventricular chamber stiffness and so does not alter passive diastolic function. In cats it also appears not to alter late diastolic filling properties. Diltiazem decreases SAM, which may decrease the amount of mitral regurgitation, but beta blockers generally produce a greater decrease in the amount of SAM. Recent evidence suggests that diltiazem has no effect on survival time in cats with severe hypertrophic cardiomyopathy and heart failure.

Dilacor XR is dosed at 30 mg per cat orally every 12 hours and produces a significant decrease in heart rate and blood pressure in cats with hypertrophic cardiomyopathy for 12 to 14 hours.

Beta-Adrenergic Receptor Blockers

Beta blockers are primarily used to reduce systolic anterior motion and heart rate in cats with hypertrophic cardiomyopathy. At this stage, beta blockers should probably be reserved for cats with severe systolic anterior motion at rest or with tachyarrhythmias and not routinely administered to the affected population as a whole, because a recent study has suggested that atenolol shortens the survival of cats with diastolic dysfunction, including cats with hypertrophic cardiomyopathy. Beta blockade is questionable for systolic anterior motion and tachycardia observed in a clinical situation. Cats spend 85% of their life asleep, and sleep probably reduces sympathetic activity better than a beta-adrenergic blocking drug. Consequently, many cats with mild to moderate systolic anterior motion in a veterinary clinic probably have no or milder systolic anterior motion at home, and the same can be said for tachycardia. Beta blockers are effective for reducing SAM. Two studies have examined the effects of esmolol, a short-acting Bradrenergic blocking drug, in cats with hypertrophic cardiomyopathy and obstruction to left ventricular outflow due to SAM; both showed a reduction in the pressure gradient across the outflow tract In both studies the degree of outflow tract obstruction decreased and the heart rate slowed, and in one esmolol was more effective than diltiazem. If the data on esmolol can be translated to atenolol’s effects in cats (which seems reasonable), one would predict that atenolol would decrease SAM.

Atenolol is a specific pVadrenergic blocking drug that needs to be administered twice a day, usually at a total dose of 6.25 to 12.5 mg orally every 12 hours. In the cat, atenolol has a half-life of 3.5 hours. When administered to cats at a dose of 1.4 mg/lb, atenolol attenuates the increase in heart rate produced by isoproterenol for 12 but not for 24 hours.


Feline Restrictive Cardiomyopathy

Although listed as a separate entity in this post, in most situations restrictive cardiomyopathy is a subclassification of unclassified cardiomyopathy. Feline restrictive cardiomyopathy is a diverse group of myocardial conditions characterized by abnormal diastolic function, normal to mildly increased left ventricular wall thickness, and normal to mildly reduced systolic function. restrictive cardiomyopathy occurs when ventricular diastolic compliance is impaired (i.e., stiffness is increased) by infiltration of the endocardium, subendocardium, or myocardium by fibrous tissue or another component. In contrast to human medicine where specific causes, such as amyloidosis and eosinophilic infiltration are causes of restrictive cardiomyopathy, specific causes for restrictive cardiomyopathy have not been clearly denned in the cat. Without the use of invasive diagnostic procedures to direcdy measure left ventricular diastolic function, DTI, other indirect measures of diastolic function, or necropsy examination, it is often impossible to distinguish this disorder from the form or forms of unclassified cardiomyopathy that are idiopathic.

Feline Restrictive Cardiomyopathy: Incidence

The exact incidence of restrictive cardiomyopathy is unknown. Unclassified cardiomyopathy is the second most common feline cardiomyopathy, of which restrictive cardiomyopathy is a component.

Cause of Feline Restrictive Cardiomyopathy

The precise cause of feline restrictive cardiomyopathy is unknown. Some evidence indicates that it may be inflammatory in nature. Endomyocarditis has been recognized in cats at postmortem examination for over 25 years. Endomyocarditis in cats is characterized by focal or diffuse infiltration of the endocardium by lymphocytes,

plasma cells, histiocytes, and a lesser number of neutrophils. The inflammatory component of endomyocarditis may be infectious, immune-mediated, or toxic. An interstitial pneumonia may also be common in this group. Within the past 10 years a study documented endomyocarditis in 37 cats at necropsy over a 7-year period. Over this same 7-year span, 25 cats with endocardial fibrosis were identified at the same institution. Four of these 62 cats had features of both diseases. This study and previous findings from Dr. Sam Liu have lead to the speculation that chronic endomyocarditis leads to endocardial fibrosis, a pathologic disease that leads to the physiologic entity termed restrictive cardiomyopathy. However, unless an agent that causes endomyocarditis in cats is identified, the theory that endomyocarditis leads to endocardial fibrosis will remain unproven.

In addition to the previous findings and speculation, one study has identified a transmissible myocarditis-diaphragmitis in young cats. The disease is generally self-limiting and causes a transient fever and depression. The investigators were unable to isolate a causative agent in these cats.

Eosinophilic endocardial inflammation is common in humans, more commonly in tropical climates. restrictive cardiomyopathy has been reported in several cats with hypereosinophilic syndrome, although it is impossible to determine if the hypereosinophilia in this small number of cats caused restrictive cardiomyopathy or the two diseases happened to occur together.

Pathophysioiogy of Feline Restrictive Cardiomyopathy

In its classic form, endocardial, subendocardial, or myocardial fibrosis impede ventricular diastolic filling and so impair diastolic function. These disorders are generally and primarily characterized by decreased compliance leading to an elevated IV diastolic pressure with a normal left ventricular filling volume. The elevation in diastolic ventricular pressure results in atrial enlargement and the formation of pulmonary edema and pleural effusion. The lesions are generally confined to the left ventricular in humans and left congestive heart failure predominates the clinical presentation. In cats, right atrial enlargement is also common. In some cats the left ventricular is perfectly normal in appearance, whereas in odiers the left ventricular may be misshapen and may have additional false tendons traversing the ventricle.

Pathology of Feline Restrictive Cardiomyopathy

The postmortem changes are unique to this form of cardiomyopathy and may be used to differentiate it from other disorders. Patchy or diffuse endocardial, subendocardial, or myocardial depositions of fibrous tissue are characteristic necropsy findings. The endocardium may appear whitish-gray, opaque, and thickened when endocardial or endomyocardial fibrosis is present. Fibrous adhesions between papillary muscles and the myocardium with distortion and fusion of the chordae tendineae and mitral valve leaflets may also be noted in restrictive cardiomyopathy. In extreme cases a portion of the left ventricular cavity, most commonly the mid-LV, may be obliterated. As with most cardiomyopathies, the left ventricular appears to be most severely affected, although other cardiac chambers may exhibit similar pathologic findings. Extreme left atrial and auricular enlargement is common. Other cats demonstrate apparendy earlier stages of the disease in which microscopic evidence of myocarditis is evident without gross pathologic abnormalities. The lesions suggest an inflammatory response; however causative factors have not been identified. Systemic thromboembolism is prevalent.

Histologic features of endocardial fibrosis include extreme endocardial thickening by hyaline, fibrous, and granulation tissue. Chondroid metaplasia is occasionally exhibited by the surface layer of hyaline tissue. A layer of loose fibrous tissue lies beneath this layer with a layer of granulation tissue adjacent to the myocardium. These changes are similar but not identical to those seen in humans with restrictive cardiomyopathy.

Natural History and Prognosis

As with other forms of cardiomyopathy, prognosis is difficult to predict for individual cases, especially prior to observing the initial response to therapy, A high incidence of serious arrhythmias, systemic thromboembolism, and refractory congestive heart failure is often present. In the author’s experience, cats with restrictive cardiomyopathy, on average, have a poor long-term prognosis. Although an initial response to standard therapy is often possible, progressive and refractory heart failure develops in the majority of cases.

Clinical Manifestations

History Signalment is difficult to accurately report, because little agreement exist among veterinary cardiologists as to which cases fall within this classification. From a series of pathologic studies in cats, Liu reported an age range of 8 months to 19 years. No breed predisposition has been reported. There may be a male predominance, or it may be that males develop more severe disease, as in hypertrophic cardiomyopathy. Most cats are middle-aged or older. Presenting complaints and clinical signs are similar to other forms of myocardial disease and include dyspnea and tachypnea, poor general condition, weakness, lethargy or rarely exercise intolerance, and anorexia. In one report, 45% had evidence of systemic thromboembolism at necropsy.

Physical Examination A heart murmur heard best on the sternum, just medial to the left apex beat, is common. An arrhythmia may be ausculted. Many cats are dyspneic.

Radiographs No specific findings exist for unclassified or restrictive cardiomyopathy. Pulmonary edema and pleural effusion are common.

Echocardiography The echocardiographic findings in restrictive cardiomyopathy are variable. Left atrial dilation is the common feature, and the left ventricular internal dimensions are typically normal but may be mildly to moderately reduced or mildly increased. Most commonly the left ventricular looks normal. However, two-dimensional echocardiography may demonstrate loss of normal left ventricular symmetry, distorted or fused papillary muscles, mild left ventricular concentric hypertrophy, mild wall thickening, a mild reduction in shortening fraction, and a mild increase in chamber diameter. Some cats may have evidence of more pronounced endocardial scarring. In these cases the endocardium may be notably thickened and irregular with an increased echogenicity. Others have evidence of cavity obliteration. Mild mitral regurgitation may be detectable with color flow Doppler. A large color flow Doppler jet suggests that the primary problem is primary mitral valve disease rather than unclassified cardiomyopathy. A left atrial thrombus may be identified.

Doppler echocardiography may be abnormal in cats with restrictive cardiomyopathy. However, this remains to be proven. As noted previously, the early diastolic waveform on DTI is reduced in cats with restrictive cardiomyopathy, whereas it is normal in cats with the idiopathic form of unclassified cardiomyopathy.

Electrocardiography No specific findings appear on electrocardiogram (ECG). Supraventricular and ventricular arrhythmias may be present, but sinus tachycardia is most commonly present in the clinic. Shifts in the mean electrical axis and evidence of chamber enlargement may occur.

Clinical Pathology No specific clinical pathologic findings exist. Azotemia due to reduced cardiac output, either from congestive heart failure or dehydration caused by diuretic therapy, is the most common abnormality. Elevated liver enzymes may be encountered.

Differential Diagnosis The primary differential diagnoses for restrictive cardiomyopathy are unclassified cardiomyopathy not due to restrictive cardiomyopathy, mitral regurgitation due to primary mitral valve disease, and myocardial infarction. Chronic myocardial infarction usually results in a region of akinetic or hypokinetic myocardium. Often the region of affected myocardium is thinner than normaJ. With severe mitral regurgitation due to primary mitral valve disease, a large jet is seen with color flow Doppler (although it may take a lower-frequency transducer and various views, including the left apical four-chamber view, to identify it). The IVS is commonly hyperdynamic, whereas the left ventricular free wall commonly moves less than normal. The left ventricular chamber is usually larger than normal in diastole.

Therapy of Feline Restrictive Cardiomyopathy

Therapy of restrictive and unclassified cardiomyopathy is the same. It is palliative and consists primarily of the administration of furosemide and an angiotensin-converting enzyme inhibitor as outlined in the two previous posts of this site. Diltiazem is not indicated because a calcium channel blocker is not able to help to relax scar (i.e., fibrous) tissue. A recent study suggests that atenolol may decrease the survival time in patients with diastolic dysfunction. However, if the cat is persistendy tachycardic at home, diltiazem or atenolol may be indicated in an attempt to slow the heart rate.