Myocardial Disease

Colin C. Schwarzwald1

Myocardial diseases are probably underecognized in clinical practice although

a variety of reports have been published regardin these disorders. There is certainly a
potential for myocardial injury or inflammation related to drugs and toxins (e.g.
ionophore antibiotics, poisonous plnats, chantaridin, snake venom), ischemia,
hypoxia, infective agents (bacterial, viral, parasitic, fungal), heavy metals, trauma,
metabolic disease or nutritional deficiences (e.g. vitamin E, selenium). Myocardial
injury also can derive from extension of a preexisting infection (pericarditis,
pericardial abscess, or endocarditis) or related sepsis. Infiltrative cardiomyopathies
can occur consequent to neoplasia (lymphoma, melanoma, lipoma,
hemangioma/hemangiosarcoma, mesothelioma, pulmonary carcinoma) or the very
rare amyloidosis.
Left ventricular hypertrophy and dysfunction may also develop secondary to
systemic hypertension associated with chronic pain, laminitis, chronic kidney disease,
or potentially metabolic syndrome. Three cases of suspected arrhythmogenic right
ventricular cardiomypathy have been described as a cause of episodic collapse and
cardiac death. Dilated cardiomyopathy (DCM) phenotype has been recognized in the
horse, but the underlying cause is generally unknown and the condition is usually
considered to be idiopathic.

Clinical Features of Myocardial Diseases

The general manifestation of myocardial disease, regardless of the underlying
injury, can be atributed to the following pathophisyologic processes:
1. Reduced myocardial contractility and ventricular ejection fraction
2. Diastolic dysfunction with impaired ventricular filling
3. Mitral or tricuspid valve incompetency caused by cardiac dilation or
papillary muscle dysfunction
4. The development of arrhythmias (atrial or ventricular premature
contractions, atrial fibrillation, atrial tachycardia etc).
The overall cardiac disability engendered by myocardial disease varies
greatly. Some horses have no detectable clinical signs; others demonstrate exercise
intolerance, life-threatening arrhythmias, low-output CHF or sudden death.
The onset of clinical signs may be behind the initial myocardial insult,
especially in cases of myocarditis or chronic myocardial injury. For example, a horse

1
Colin C. Schwarzwald, 2018 – Disorders of the Cardiovascular System. In: Stephen M. Reed, Warwick M.
Bayly, Debra C. Sellon. Equine Internal Medicine. Fourth Ed. Elsevier.
that has a apparently recovered from an ilness may develop problems once rigorous
training is begun. The trainer may complain that the horse is unable to achieve faster
speed or may stop or suddenly slow during hard training. The affected horse may take
a long time to „cool out” after a workout. In more severe cases, marked exercise
intolerance, weakness, ataxia or even collapse may occur. Respiratory distress,
pulmonary edema, cyanotic mucous membranes, prolonged capillary refil time and a
rapid thready pulse may be detected after exercise. In case of several myocardial
inujury, signs such as fever, persistent tachycardia, arrhythmia, murmur, pulmonary or
ventral edema or respiratory distress may be observed. Sudden death may occur
without premonitory signs.
Results of the clinical examination in horses with myocardial disease are
inconsistent. Resting physical examination findings can be normal or signs of heart
disease may be evident These can include persistent tachycardia, tachypnea, frequent
premature beats, sustained arrhythmias, systolic murmurs of AV valvular
insufficiency or CHF (congestive heart failure). A postexercise examination often
detects an abnormally rapid heart rate, which remains persistently hisgh after exercise
is discontinued (note that exercise testing should not be performed in horses with
persistent resting tachycardia or tachyarrhythmia that may be attributed to myocardial
disease).
An ECG may demonstrate sinus tachycardia or atrial or ventricular
arrhythmias. An exercise ECG, in addition to potential exercise-induced arrhythmias,
typically records an inappropiately high heart rate for the level of work undertaken.
Resting echocardiography usually reveals a low normal or unambiguously
reduced ventricular systolic function, as demonstrated by low LV (left ventricle)
shortening fraction or ejection fraction. Novel echocardiographic methods such as
tissue Doppler imaging (TDI) or 2D speckle tracking might be more sensitive to
detect LV systolic dysfunction compared with conventional 2D – Echo or M-mode
echocardiography and could be particularly useful to detect subtle myocardial disease
in horses. Furthermore, Doppler interrogation of transmitral blood flow (E and A
wave) and LV wall motion anaysis using TDI can reveal significnt LV diastolic
dysfunction in the presence of normal or impaired systolic function strongly
suggesting myocardia disease.
Depending on the type of myocardial disease, the (relative) LV wall thickness
can be increased (i.e. infiltrative or hypertensive cardiomyopathy) or decreased (i.e.
dilated or tachycardia-induced cardiomyopathy). Postexercise echocardiography may
demonstrate a paradoxic reduction of LV shortening fraction or regional dysfunction
characterized by LV wall motion abnormalities. Marked increases in left ventricular or
left atrial spontaneous contrast may be observed with very poor myocardial function,
although this is not a specific finding. Abnorma areas of myocardial echogenicity
have been observed, but myocardial tissue characterization by echocardiography is not
well established in horses nd grayscle also depends on technical factors.
Clinical laboratory tests may be useful in the identification of myocardial
dmage but may not necessarily distinguish myocarditis from myocardial cell injury
induced by a toxin or by ischemia. Elevated plasma or serum creatine kinase activity
(CK), myocardial fractions of creatine kinase (CK-MB) or lactate dehydrogenase
(LDH1 – 2) suggest myocardial injury. A more specific marker of myocardial is
elevation of plasma cardiac troponin I (cTnI) or troponin T (cTnT). Although normal
values or mild elevations do not exclude cardiomyoopathy or myocardial infiltration,
markedly elevated values (i.e. cTnI greater tahn 1ng/mL) point to recent cardiac
muscle damage. Persistently elevated plasma cTnI concentrations indicate ongoing
damage, because plasma half-life of cTnI is short.
Diagnosis of myocardial disease requires clinical suspicion and integration of
findings from clinical and laboratory examinations. Because of the extreme
variability of findings, the presumptive diagnosis of myocardiak disease can be made
only after reviewing the history, physical examination, echocardiogram, ECG and
clinical laboratory tests. Definitive diagnosis of myocarditis requires transvenous
endomyocardial biopsy, but this test is currently limited to research purposes and may
not identify piecemeal inflammation, degeneration infiltration or necrosis.
Treatment of horses affected by myocardial disease is primarly supportive.
Prognosis depends on the cause and severity of myocardial injury and the
hemodynamic consequences of myocardial disease. All horses should be rested,
preferably in a stall, until myocardial function, ECG and plasma troponin
concentrations return to normal or at least remin stable for several weeks. A minimum
rest of 1 month (and usually more) should be instituted before a horse is returned to
work. Supplementation with vitamin E and selenium may be beneficial, particularly
in cases with suspected nutritional deficiences. Antiarrhythmic therapy is administered
when indicated for potentially life-threating arrhythmias. Theoretically, an ACE
inhibitor will reduce myocardial remodeling and unload the ventricle, assuming the
drug can be sufficiently absorbed and biotransformed to an active state; however,
efficacy of this treatment is currently unknown. When CHF (congestive heart failure)
has develop, diuretics, peripheral vasodilators and positive inotropic agents may be
prescribed as previously discussed in the section on CHF. Digitalization should be
undertaken with caution in horses with ventricular extrasystoles (prematures
ventricular beats), as the arrhythmia may be aggravated and it is not indicated in
ionophore toxicosis.
For a suspected bacterial etiology, antibiotic treatment is indicated. IF
noninfective myocarditis is believed to be the cause of the arrhythmia or clinical signs,
corticosteroid therapy may be indicated, although its value is unsubstantiated. When
the principal manifestation of myocardial disease is electrical (arrhythmia with
otherwise normal myocardial function), the prognosis is fair to good for resolution of
the arrhythmias. Horses with decreased mycardial function by echocardiograhy or
those with CHF must be given a guarded prognosis for life and a poor prognosis for
future performance. It is notable, however, that some horses with left ventricle
hypertrophy and dysfunction and some with acute onset of CHF have recovered
completely and returned to their prior performance level. Such horses most likely
suffered from acute myocarditis that resolved spontaneously or following
antiinflammatory therapy. Other horses may achieve a less spectacular recovery but
still serve succesfully as breeding animals.

Myocarditis

Myocardial inflammation or myocarditis is difficult to diagnose. The

diagnosis is often entertained in horses with cardiac arrhythmias, concentric LV (left
ventricle) hypertrophy (supposedly acute myocarditis with cell infiltration and
myocardial edema) or severe LV dilation (supposedly chronic or later stages) and
abnormal myocardial function, particularly when cardiac signs occur after another
illness and are associated with elevated cardiac isoenzymes or plasma cTnI or cTnT
concentrations.
Often the prior disorder is a viral, influenza – type condition or an infection
caused by Streptoccocus spp., but parasitic migration, fungal infections or toxic insults
can also result in inflammatory myocardial lesions that may not obviously be
associated with preceding clinical disease. It is logical that immune – mediated
myocarditis is operative in many of these cases, but definitive cause-and-effect proof
is lacking. Myocarditis may also follow pericarditis or infective endocarditis.
Hematogenous spread to the heart may be another mechanism for myocarditis.
The signs, prognsis and treatment of mycarditis are similar to that described in
the preceding section.

Toxic Injury of the Myocardium

A number of chemicals and plant toxins are potentially injurious to the

myocardium. Ionophore antibiotics re among the most notorius causes of myocardial
necrosis in horses. Toxic myocardial injury also can occur following ingestion of
glycoside-containing yew plants (taxus spp.), oleander (Nerium oleander), foxglove
(Digitalis spp.) and summer pheasant’s eye (Adonis aestivalis) or from eting feed
contaminated by Epicauta species (blister beetles), which contain the toxic element
cantharidin. Atypical myopathy (AM) and sesonal pasture myopathy (SPM) that are
caused by ingestion of hypoglycin A-containing seeds of maple trees (Acer spp.) and
marshmallow (Malva parviflora) toxicosis, through different muchanisms can cause
severe generalized myopathy with myocardial involvement/damage.
Myocardial necrosis has also been observed in association with clostridial
infection and following endotoxemia, particularly with salmonellosis and torsion of
the large colon. Venom of rattlesnakes (Crotalus spp.) and of other members of the
family of vipers (Viperidae) has been associated with cardiac injury and arrhythmias.

Ionophore Toxicity

Horses are uniquely sensitive to ionophore antibiotics, which are used as a

coccidiostat in poultry production and as a growth promoter in cattle. Monensin
toxicosis (acute oral LD50 2 – 3 mg/kg) has occured most frequently but salinomycin
(acute oral LD50 0.6 mg/kg) and lasalocid (acute oral LD 50 21.5 mg/kg) also have
caused myocardial injury anddeath in horses. Ionophores react with polar cations ti
form lipid-soluble complexes, leading to cation transport across myocardial cell
membranes. Various ionophores demonstrate particular affinities for different cations,
though lasalocid may complex with a variety of ions. Exposure of horses to the
ionophore antibiotics ussualy stems from accidental contamination of equine
feedstuffs at the mill or through accidental delivery of poultry or cattle feed to horses.
In most outbreks, a recently acquired ration was fed.
Clinical signs of horses with ionophore toxicity vary with the specific type,
quantity and concentration of ionophore ingested and the preexisting health and body
condition of the exposed horses. A wide range of clinical signs has been observed in
exposed horses ranging from none to clinical signs involving almost all body systems.
Weakness, lethargy, depression, anorexia, ataxia, colic, diarrhea, profuse sweating and
recumbency have been seen. The cardiac findings are similar to those previously
described for myocardial diseases. If sudden death occurs, it is usually within 12 to 36
hours of ingestion of the contaminated feed. A single dose may lead to peeracute
death from cardiac arrhythmias before the development of myocardial necrosis and
associated with only mild signs of colic or neurologic deficits.
Sublethal toxicosis may be well tolerated by some but not all horses, and
plasma cTnI concentrations, echocardiography and exercise testing may help to
identify horses affected more severely. Polyuria and hematuria are other signs that
have been reported in ponies following ionophore exposure.
A diagnosis of ionophore toxicity is based on the detection of the ionophore in
the feed or stomach contents of exposed horses. Various clinicopathologic
abnormalities are observed with monensin toxicity, including decreased serum
calcium, potassium, magnesium, and phosphorus and increases in serum urea,
creatinine, unconjugated bilirubin, aspartate aminotransferase, and muscle enymes.
Elevated concentrations of plasma cardiac troponin (cTnI, cTnT) and isoenzyme
patterns of CK and LDH have indicated cardiac, skeletal, and RBC damage. Elevated
packed cell volume and total solids have been associated with dehydration.
Echocardiographic evaluation of affected horses has revealed marked decreases in
shortening fraction with segmental wall motion abnormalities that range from mild to
severe.
Prognostically, horses that exhibit decreased shortening fraction and
diskinesis shortly after exposure to monensin generally are unlikely to survive. Horses
with mild decreases in shortening fraction survive and may be useful breeding
animals, but most do not return to previous performance levels. Horses with normal
echocardiograms typically survive and may return to work at their previous level. The
magnitude of increase in plasma cTnI or cTnT concentrations and rate of decrease
over time likely has some prognostic implications; however, even in surviving animals
concentrations can remain increased for several months, likely because of ongoing
release from damaged myocytes. Postmortem findings range from no visible lesions to
myocardial pallor and signs of CHF. Severe myocardial necrosis and fibrosis has been
observed in horses with decreased shortening fraction or ventricular dyskinesis on
echocardiography.
Treatment for affected horses is largely symptomatic, unless very recent
exposure is known. Vitamin E has been suggested to have a protective effect in other
species and may be beneficial in affected horses. Digoxin and calcium channel
blockers re contraindicated in acutely affected horses. If ingestion of the contaminated
feedstuff is recent, treatment with activated charcoal or mineral oil is indicated to
reduce absorption of the ionophore. Intravenous fluid and electrolyte replacement
therapy may be indicated, as well as antiarrhythmic drugs, for any life-threatening
arrhythmias. Stall rest in quiet environment for up to 8 weeks after exposure is most
important, because echocardiograms recorded after trivial exercise or excitement can
revel residual disease characterized by marked decreases in fractional shortening and
myocardial dyskinesis.

Dilated Cardiomyopathy

Idiopathic dilated cardiomyopathy (DCM) is a disorder of the myocardium

characterized by global reduction of LV systolic function that cannot be explained by
valvular, vascular, coronary or congenital heart disease. The inciting cause of dilated
cardiomyopathy is generally undetermined, although myocarditis or prior toxic injury
is often suspected. Relentless junctional or ventricular tachycardia also can lead to a
DCM state that is reversible with control of the tachyarrhythmia.
 The clinical signs of cardiomyopathy are similar to those described earlier for
other myocardial diseases. Echocardiography is diagnostic, revealing cardiomegaly
with biatrial and biventricular dilation and depressed shortening fraction.
Symptomatic therapy with digoxin and diuretics may temporarily stabilize
CHF and lead to transient improvement, but most horses deteriorate in the 3 to 12
months after diagnosis and are humanely destroyed. Neither the history nor the
postmortem examination reveals the cause and generally only diffuse or multifocal
myocardial degeneration, necrosis and fibrosis are observed.
A form of dilated cardiomyopathy also can be caused by vitamin E and
selenium deficiency and is observed primarily in fast-growing foals from mares with a
marginal or deficient selenium status raised in selenium-deficient areas. Affected foals
are usually younger than 6 months of age and present with an acute onset of weakness,
recumbency, respiratory distress, pulmonary edema, tachycardia, murmurs, and
arrhythmias. The prognosis for foals affected with the myocardial manifestations of
white muscle disease is poor, and most die within 24 to 48 hours after the onset of
clinical signs.
Laboratory abnormalities in affected foals include marked elevations of CK
(including the MB fraction in foals with myocardial involvement), aspartate
aminotransferase aminotransferase (AST) and LDH, as well as hyperkalemia,
hyponatremia and hypochloremia. Myoglobinuria may occur. Echocardiography
demonstrates the severity of myocardial involvement Whole blood selenium, RBC
glutathione peroxidase, and vitamin E concentrations may be helpful in the diagnosis;
however, tissue samples provide a more accurate indication of selenium stores.
Treatment with selenium and vitamin E might be successful, but typically the
myocardial necrosis is extensive and incompatible with life. Postmortem findings
reveal pale streaking of the myocardium with intramuscular edema, myodegeneration,
myocardial necrosis, and fibrosis or calcification. Prevention of white muscle disease
is important in selenium-deficient areas. Supplementation of pregnant mares should
occur during gestation based on individual blood and tissue selenium concentrations
and should be continued during lactation, because more selenium is passed to the foal
through the milk than across the placenta.