Session #3003
Abstract
Cardiovascular disease, including atherosclerosis, congestive heart failure, and pericardial disease, commonly occurs in companion birds. Treatment approaches are largely empirical and extrapolated from small animal and human medicine; there is a paucity of pharmacokinetic and pharmacodynamic data and no clinical trials in birds for cardiovascular therapeutic agents used in mammals. Nevertheless, there are numerous medications, including diuretics, vasodilators, positive and negative inotropes, and antiarrhythmic agents, that can be employed in the treatment of cardiovascular disease in avian species. Although long-term prognosis in most cases is guarded to poor, the treatment options and management strategies outlined in this review have the potential to maintain quality of life and extend survival time in these patients.
Introduction
Cardiovascular disease is frequently encountered in avian practice, predominantly in psittacine birds, and poses a serious threat to the quality of life and longevity of these and many other avian species. Successful intervention requires a foundational understanding of relevant anatomy and physiology, heightened awareness of risk factors and clinical disease states, accurate and timely diagnosis, and innovative treatment approaches.
At the present time, therapeutic interventions for cardiovascular disease in birds are largely empirical and extrapolated, where possible, from small animal and human medicine. Treatment has also been guided by a growing number of case reports in which treatment was attempted. These include cases of vascular disease, such as atherosclerosis and its associated pathologies of stroke and intermittent claudication, cardiac disease, arrhythmias, congestive heart failure (CHF), and pericardial disease and effusion.
The long-term prognosis for most cardiovascular diseases is considered guarded to poor, given that treatment is limited to management for a finite period, rather than resolution of disease in most cases. Prognosis is partly contingent on timely diagnosis, which proves challenging given the absence or subtlety of clinical signs and the limited sensitivity of available diagnostic modalities before the disease has become advanced. Primary goals are to identify and control risk factors, where possible, and following diagnosis of cardiovascular disease, to maintain quality of life and extend survival time. The following sections review treatment options that show promise for the management of recognized disease states in birds, including atherosclerotic disease, CHF and related conditions, and pericardial disease and effusion.
Atherosclerosis
Atherosclerosis is a chronic inflammatory and degenerative disease of the arterial wall wherein the lumen narrows by progressive accumulation of fibro-fatty atheromatous plaques within the intima. Advanced lesions are characterized by severe arterial stenosis and occlusion, and by calcification and osseous metaplasia. Atherosclerosis is likely an underlying factor in the majority of non-infectious cardiovascular diseases in pet birds. Lesions are most frequently recognized in the ascending aorta, brachiocephalic trunks, and pulmonary arteries, but occur in the peripheral vasculature as well (notably the coronary and carotid arteries, descending aorta, subclavian arteries, coeliac artery, and ischiatic arteries). Prevalence is highest in grey parrots (Psittacus spp.), Amazon parrots (Amazona spp.), and cockatiels (Nymphicus hollandicus). Other risk factors include increasing age, female sex and female reproductive activity, high-calorie, fat, and cholesterol diets, dyslipidemia (e.g., hypercholesterolemia, hypertriglyceridemia), and limited physical activity.
Clinical signs are attributed to advanced lesions, whereas early and intermediate lesions are generally silent and subclinical. Unlike humans, recognizable clinical disease is primarily the product of progressive, flow-limiting arterial stenosis rather than thromboembolism and acute arterial obstruction. Clinical signs vary depending on the vessels affected, severity of atherosclerotic lesions, and presence of concurrent disease, including cardiac disease and CHF. Patients often present for falling or collapse, frequently accompanied by transient or persistent weakness and dysfunction of one or more limbs. Exercise-induced intermittent weakness and pain in the pelvic limbs, resolving with rest, is termed intermittent claudication. There may be persistent neurologic abnormalities identified upon physical examination, including reduced mentation, blindness, anisocoria, seizures, vestibular signs, paresis of one or both pelvic limbs, and ataxia. These signs are considered most consistent with stroke, but rarely is this confirmed diagnostically.
Treatment of atherosclerosis involves both controlling risk factors and managing sequelae, including peripheral hypoperfusion, intermittent claudication, ischemic stroke, and CHF. Atherosclerotic lesions cannot be resolved, but diet, husbandry, and lifestyle changes may help to prevent, slow progression, or decrease the size of lesions. Medical management focuses primarily on improving peripheral perfusion. Peripheral vasodilators, used either singly or in combination, may have symptomatic benefit by decreasing vascular resistance and reducing afterload.
Vasodilators
Isoxsuprine
Isoxsuprine is a peripheral vasodilator that causes vascular smooth muscle relaxation predominately through α-adrenoceptor blockade. To a much lesser degree, it is a β-adrenoreceptor agonist and, as such, may have positive chronotropic and inotropic effects (via β-1 adrenoreceptors) and further vasodilatory effects (via β-2 adrenoreceptors). In addition, it is known to increase erythrocyte deformability in humans. In veterinary medicine, isoxsuprine is used to increase peripheral blood flow in horses with vascular disorders of the lower limb and to address trauma-induced wing tip edema in raptors. In a published report, a 35-year-old yellow-naped Amazon parrot with presumptive atherosclerosis was treated with isoxsuprine (10 mg/kg PO q 24 h). Clinical signs of lethargy, weakness, hyporexia, weak grip, and ataxia resolved with treatment, and repeatedly recurred when the drug was discontinued, again resolving once it was reinstituted. The author has observed similar, apparent symptomatic improvement when using isoxsuprine (10–15 mg/kg PO q 12 h) in numerous cases of clinical, presumed atherosclerosis (some of which were later confirmed at necropsy and by histopathology). Many of these patients have been treated and followed for several months to several years, over which time frequency and severity of stroke-like events, intermittent claudication episodes, and other clinical signs appeared to decrease.
Angiotensin-Converting Enzyme Inhibitors (ACEI)
ACEI, including enalapril, result in vasodilation by blocking the formation of angiotensin II (AII). AII promotes vasoconstriction and venoconstriction by mediating the release of catecholamines, which act on vascular smooth muscle via α-adrenergic receptors. By blocking the formation of AII, ACEI reduce both total peripheral resistance and pulmonary vascular resistance. Although the relative vasodilatory effect of an ACEI compared to isoxsuprine in birds is not known, it is conceivable that the two used in combination would have synergistic effects: an ACEI by limiting α-adrenoreceptor stimulation and isoxsuprine by α-adrenoreceptor antagonism. The author has treated patients with clinical (presumed) atherosclerotic disease using enalapril at a dose and frequency of 1.25–5 mg/kg PO q 8–12 h. In more severe cases, this is paired with isoxsuprine.
Sildenafil
Sildenafil is a selective pulmonary vasodilator that reduces pulmonary vascular resistance and right ventricular afterload. It has predominantly been used for the treatment of pulmonary hypertension (PH) in humans and dogs. In birds, the drug may have merit in cases with suspected atherosclerosis of the pulmonary arteries, potentially in combination with other vasodilators.
Other Medical Management
Pentoxifylline
Pentoxifylline has been used in human medicine for the treatment of peripheral vascular and cerebrovascular disease by improving microcirculatory blood flow. In small mammal models, the drug was found to increase tissue perfusion, mitigate inflammation, and attenuate atherosclerotic plaque formation. Based on these findings, pentoxifylline may have value in improving peripheral perfusion in birds with atherosclerotic disease, including those with concurrent polycythemia. The author has used it for these indications in numerous psittacine patients (15–25 mg/kg PO q 8–12 h).
Statins
Statins are a group of lipid-lowering drugs used extensively in human medicine for their anti-atherosclerotic effects through inhibition of cholesterol synthesis and other mechanisms. Several products are commercially available for human use, including atorvastatin (Lipitor®) and rosuvastatin (Crestor®). Statins have been employed empirically in psittacine birds, but their use is controversial because target lipid levels that would reduce atherosclerosis risk are unestablished, and because their efficacy is not supported by available pharmacodynamic and pharmacokinetic data. Consequently, the author does not recommend the use of statins in psittacines considered either to have or to be at risk for atherosclerotic disease. Instead, vasodilatory therapy (for symptomatic patients) and dietary and lifestyle changes to prevent and address dyslipidemia are more appropriate.
Supportive Care and Husbandry Considerations
In addition to medical treatment, patients with clinical atherosclerosis and associated disease can benefit greatly from the following measures:
Supportive Care
Patients with signs of stroke may have marked neurologic deficits including reduced mentation, limb paresis, and ataxia that prevent normal eating and drinking and impair mobility. They may experience seizures or suffer injuries from falls. Supportive care measures to consider for these patients include fluid and nutritional support, analgesia, anticonvulsant therapy when needed, and management of secondary conditions such as trauma and aspiration pneumonia. Benzodiazepines diazepam (0.5–2 mg/kg IM) or midazolam (1–2 mg/kg IM) can be used for emergency control of seizures. Options for longer-term anticonvulsant therapy are levetiracetam (50–50 mg/kg PO q 8–12 h), zonisamide (20 mg/kg PO q 8–12 h), and gabapentin (15–20 mg/kg PO q 8–12 h). The author has used levetiracetam alone or in combination with zonisamide and gabapentin to control seizure activity in psittacine birds with severe atherosclerotic disease.
Exercise Restriction Versus Promotion of Exercise
For patients with advanced, clinical atherosclerotic disease, exercise restriction should be part of the longer-term treatment plan, as well as appropriate housing modifications to accommodate and protect birds with persistent deficits. In contrast, increasing opportunities for exercise (especially flight) from early in life may have preventative value. Physical activity can be promoted through training and by designing captive environments to facilitate locomotion and foraging behaviors.
Dietary Management
Dietary management to avoid dyslipidemia may have both therapeutic and preventive value, particularly for at-risk species. Such measures include:
- Moderation of dietary calories and fat and prevention and resolution of obesity
- Provision of formulated (rather than seed-based) diets, supplemented with fresh vegetables and fruits
- Avoidance of dietary sources of cholesterol (animal-based products)
- Supplementation with omega-3 fatty acids, particularly α-linolenic acid (found in flaxseed oil), has been shown to improve lipid metabolism, reduce inflammation, and minimize development (or slow progression) of atherosclerosis in several avian species.
Other
- Along with dietary changes, control of female reproductive activity may help prevent atherosclerotic disease.
- For patients receiving medications long-term, training to allow low-stress administration is indicated.
Congestive Heart Failure
CHF occurs when the heart is unable to empty the venous reservoirs, manifested by vascular congestion and transudation of fluid within tissues and body cavities (congestive signs). In the case of right-sided CHF, peripheral venous congestion, hepatic congestion, ascites, and pericardial effusion are often present. Pulmonary edema and congestion of the pulmonary veins occur with left-sided CHF, and a combination of signs may be seen with biventricular failure. Heart failure can further be characterized as systolic (inadequate ventricular ejection), diastolic (inadequate ventricular filling), or a combination of the two. In either scenario, stroke volume and cardiac output decrease.
CHF is not a primary disease in itself, but an ultimate consequence of structural or functional abnormalities of the cardiovascular or pulmonary systems, compounded by the chronic effects of compensatory mechanisms. Not all cardiovascular disease necessarily leads to CHF, but it is a frequent clinical end-point encountered in avian species. Heart failure can result from primary myocardial failure, including dilated cardiomyopathy (DCM), ventricular pressure overload (as occurs with outflow obstruction and systemic or pulmonary hypertension), or volume overload (as occurs with valvular insufficiency), conduction disturbances, or diastolic dysfunction (as occurs with myocardial hypertrophy and cardiac tamponade).
In a patient presenting with acute or decompensated heart failure, initial treatment aims to stabilize the patient, followed by the design of a longer-term management strategy. In the author’s experience, this has met with highly variable success, but some birds have been maintained in stable condition for up to 9 years.
The mainstays of treatment of CHF in small animal medicine, namely diuretics, vasodilators (including ACEI), and positive inotropes, can be applied to the treatment of the condition in birds. Beta-blockers (BB), considered part of standard treatment in humans, may also have potential application. In addition, the known or hypothesized underlying cause(s) should be addressed, if possible. Some etiologies, including bacterial and fungal infections, parasitic disease, and certain toxic insults, carry a better prognosis for recovery.
Diuretics
Marked reduction of excessive circulating plasma volume (hypervolemia), edema, and effusion is an immediate treatment priority in any avian patient with CHF. Alleviation of this relative fluid overload can be accomplished through the use of diuretics, principally furosemide. Diuretics should not be used alone long-term as they further activate the renin-angiotensin-aldosterone system (RAAS). Of the various diuretics available, furosemide is most commonly used in companion birds.
Furosemide
Furosemide is a potent loop diuretic that inhibits the sodium, potassium, and chloride cotransporter in the ascending limb of the loop of Henle, thereby promoting diuresis and excretion of sodium and chloride. Parenteral administration of furosemide is an essential step in the management of the acute crisis in avian patients as this route allows for a rapid onset of action. A relatively high initial dose is often required. Following stabilization of the patient, a maintenance dose of furosemide can be used to enable the long-term management of chronic CHF.
Furosemide has been found to be efficacious with a rapid onset of action in birds, despite the presence of only 10–30% of looped nephrons in the avian kidney. It has been used successfully for the treatment of pericardial effusion, CHF, pulmonary edema, and ascites. Route of administration may significantly influence bioavailability, as suggested by the results of a study examining the diuretic effects of furosemide in chickens (adult laying hens). In this study, it was found that urine output significantly increased following parenteral administration (2.5 mg/kg), but did not in birds receiving the drug orally, even at twice the parenteral dose (5 mg/kg).
Doses that have been used vary widely. Similar to dogs and cats, the dose and administration interval is best determined by clinical response (namely normalization of respiratory rate and effort) balanced with the maintenance of acceptable hydration. The degree of clinical response can be of diagnostic and prognostic value; a positive response supports the working diagnosis of CHF and suggests a more favorable prognosis. Alternatively, a poor response warrants reevaluation of the working diagnosis or, if the diagnosis is sound, suggests a poorer prognosis. In the author’s experience, a dose range of 1–5 mg/kg intramuscularly (IM) has been efficacious when stabilizing most psittacine patients. An initial frequency of 2 hours is usually followed by a shift to 6- to 12-hour intervals. There have been isolated cases with severely decompensated disease in which higher doses (7–11 mg/kg IM q 12 h) were required to gain control of congestive signs. In patients whose disease is less severe and advanced, a lower initial dose and frequency (1–5 mg/kg IM q 12 h) may be adequate. Once the patient has been stabilized, furosemide can be administered orally, with the dose increased at least 2-fold (presuming oral bioavailability is 60–75% as in humans) given q 8–12 h. Ultimately, the goal for long-term management is to identify the lowest dose and frequency that controls congestive signs; adjustments will be needed over time as the disease condition changes or progresses. Patients with more severe, advanced disease may require a higher dose and frequency (30–70 mg/kg PO every 6–12 hours) to maintain control of congestive signs.
Spironolactone
Spironolactone, an aldosterone antagonist that is classified as a potassium-sparing diuretic, may have merit as part of the treatment regime in cases where congestive signs cannot be controlled with furosemide and an ACEI alone. Its combined use with furosemide may also be considered to offset potassium loss. Aside from its diuretic effects, spironolactone is thought to prevent or decrease myocardial fibrosis in humans, and counteract the myriad deleterious effects of aldosterone in CHF; however, thus far, reports on its use or efficacy in avian species are scarce. In the author’s experience, doses between 1–13 mg/kg PO q 8–12 h have been well tolerated in numerous CHF patients.
Vasodilators
ACEI
ACEI are typically combined with diuretics and positive or negative inotropes and comprise an essential component of long-term medical management of CHF by blunting the effects of the RAAS. By interfering with AII formation and limiting aldosterone production, ACEI promote vasodilation and reduce sodium and water retention, thereby decreasing total peripheral resistance and pulmonary vascular resistance (afterload) and circulating volume (preload), allowing an increase in cardiac output. Enalapril is thought to attenuate myocardial remodeling in humans and dogs. In both species, ACEI have been found beneficial to increase survival times.
Of the different ACEI that are available, enalapril has been the most commonly used in birds, with empirical evidence suggesting it is both safe and efficacious. Enalapril has been used, both alone and in combination with furosemide, to treat CHF with a reduction in pericardial effusion, ascites, and hepatic congestion documented by echocardiography, and reportedly increased quality of life and longevity in birds with severe cardiac pathology. The author has found that when edema and effusion are mild, they can, in some cases, be resolved with enalapril alone without concurrent use of a diuretic. Pharmacokinetic data supports a dose of at least 1.25 mg/kg PO q 8–12 hours in pigeons and Amazon parrots, although the half-life was shorter and lower maximum plasma concentrations were reached in the latter species. As a result, the author has used higher doses (4–11 mg/kg PO q 8–12 h) in psittacine birds with appreciable symptomatic benefit and no apparent adverse effects.
Sildenafil
Compared to mammals, birds are thought to have a greater propensity for developing PH and right-sided, rather than left-sided CHF. The inclusion of sildenafil should be considered in the treatment of CHF patients with cor pulmonale. The author has used sildenafil for this indication in psittacine birds at a dose and frequency of 1–11 mg/kg PO every 8–12 hours.
Positive Inotropes
Positive inotropes such as digoxin and pimobendan have been used or proposed for the treatment of heart failure in avian species, but pharmacodynamic data is lacking and pharmacokinetic data and information as to their efficacy and margin of safety is extremely limited. Both drugs are used to enhance myocardial contractility and are appropriate for the treatment of heart failure due to systolic dysfunction. They are contraindicated in cases of hypertrophic cardiomyopathy (HCM), where diastolic dysfunction is the primary problem, and in outflow obstruction (such as aortic stenosis). Likewise, it should be questioned whether their use is appropriate in birds with heart failure secondary to atherosclerotic disease and luminal stenosis of major arteries. In those cases with severe systolic dysfunction, however, it is fair to consider their inclusion in the treatment regime in an effort to stabilize the patient, if not also to manage CHF over the longer term. Once the patient has been stabilized, the clinician can also consider either alternative or concurrent use of a BB (see the following section). Digoxin may have value in certain heart failure cases, particularly when supraventricular tachyarrhythmia is a feature.
Pimobendan
Pimobendan, a calcium sensitizer and phosphodiesterase inhibitor, is a positive inotrope and vasodilator (inodilator), as well as a positive lusitrope. It enhances myocardial contractility, primarily through calcium sensitization of cardiac myofibrils and by phosphodiesterase III inhibition, without increasing myocardial oxygen consumption. Inhibition of phosphodiesterase III and V promotes systemic and pulmonary arterial and venous dilation, thereby reducing afterload and preload, respectively. Pimobendan is commonly used in small animal cardiology and has been shown to increase both survival time and quality of life in dogs with dilated cardiomyopathy and heart failure secondary to mitral valve disease.
A pharmacokinetic study in Hispaniolan Amazon parrots (Amazona ventralis) demonstrated that a single oral dose of 10 mg/kg is required to achieve a peak plasma concentration of 8.26 ng/ml, comparable to levels considered therapeutic in dogs and humans. Extrapolation of the dose used in this study to other species groups should be done with caution. Plasma concentrations in a Harris hawk (Parabuteo unicinctus) with CHF receiving 10 mg/kg pimobendan PO peaked at 25,196 ng/ml; however, there was no indication of toxicosis.
Bio-availability of pimobendan can be affected by pharmacologic composition. An oral suspension formulated from commercially-available tablets (crushed and combined with a suspending vehicle) produced 6 times greater plasma concentrations than a suspension made from the bulk chemical (powder). The authors proposed that the difference might be attributed to the citric acid excipient present in the commercially-available tablets, which facilitated oral absorption.
The author has incorporated pimobendan (6–20 mg/kg PO every 8–12 hours) into the treatment regime for management of CHF in many companion birds.
Negative Inotropes
Negative inotropes, including BB and calcium channel blockers (CCB), may have merit as adjunctive treatments for CHF, particularly when ventricular hypertrophy and tachyarrhythmia are contributing factors.
Beta Blockers
BB are sympatholytic agents that block the binding of endogenous catecholamines to β-adrenoreceptors. They are negative inotropes, chronotropes, and lusitropes that also slow AV nodal conduction:
- First-generation, non-selective BB (e.g., propanolol, carteolol, sotalol) block both β1- and β2-adrenoreceptors.
- Second-generation BB (e.g., atenolol, metoprolol) are relatively β1-selective.
- Carvedilol, a third-generation BB, is both a non-selective β-adrenoreceptor antagonist and a selective α1-adrenoreceptor antagonist, such that it also has vasodilatory action to reduce afterload.
BB are considered part of the core therapy for heart failure in humans, both in early and advanced stages. They counter the increased sympathetic tone and RAAS activation characteristic of the neuroendocrine system that is central to the pathogenesis and progression of CHF. By retarding its deleterious effects, β-blockade is beneficial in the treatment of heart failure, ultimately improving systolic function in spite of the attendant negative inotropic effect. Longer-term actions of BB include regression of myocardial hypertrophy, reversal of remodeling, and normalization of ventricular geometry. In addition, the antioxidant properties of some BB, including carvedilol, may also contribute to their beneficial effects. In human cardiovascular medicine, second- and third-generation BB are utilized in combination with diuretics and ACEI for the treatment of chronic, stable CHF related to left ventricular systolic dysfunction (including DCM).
In dogs, these drugs have also garnered interest as an adjunctive treatment for CHF, though their efficacy has not yet been established. BB and ACEI are also used in humans to prevent heart failure in cases with structural cardiac abnormalities (such as left ventricular hypertrophy and valvular disease) and systolic dysfunction that are as yet asymptomatic. Similarly, BB have been suggested as part of the treatment for preclinical chronic degenerative AV valve disease (CVD) and preclinical DCM in dogs, as they might delay progression to heart failure.
The beneficial effects of BB have been documented in avian models of heart failure. The author suggests that BB may have application in avian cardiology as an adjunctive treatment of CHF, provided the condition is first stabilized using conventional management strategies. The author has used carvedilol (1–9 mg/kg PO q 12–24 h), in conjunction with a diuretic(s) and an ACEI, as part of treatment for CHF in psittacines, specifically when concentric ventricular hypertrophy, tachycardia, and diastolic dysfunction were features. Concurrent administration of a positive inotrope, such as pimobendan, during the period of BB uptitration may allow patients to tolerate initiation of treatment.
Calcium Channel Blockers
CCBs, including nifedipine, verapamil, diltiazem, and amlodipine, inhibit the influx of extracellular calcium ions across cardiomyocyte and vascular smooth muscle cell membranes, thereby inhibiting contraction. Effects are negative inotropy and chronotropy, slowing of the sinus rate and AV nodal conduction, and vasodilation. CCB are classified by their relative selectivity for the vasculature or for the myocardium; those that predominantly promote peripheral vasodilation and reduce total peripheral resistance (nifedipine and amlodipine) are indicated primarily for the treatment of hypertension, and those that influence conduction (verapamil and diltiazem) are indicated for the treatment of supraventricular tachyarrhythmias. Adverse effects of CCB include bradycardia, hypotension and reflex tachycardia, and AV block. Contraindications include SA nodal dysfunction, second- or third-degree AV block, and decompensated heart failure.
In human heart failure patients with systolic dysfunction, CCB confer no survival benefit and may exacerbate the condition. Nevertheless, CCB warrant mention because their cardioprotective effects have been investigated in avian models of heart failure and found to rival those of BB. Both nifedipine and verapamil are cardioprotective (nifedipine>verapamil), but the mechanisms by which these drugs confer their benefits are unknown.
Treatment of Related Conditions
CHF may be accompanied by disease processes such as HCM, systemic and/or pulmonary hypertension, and arrhythmias. These conditions thus deserve special consideration.
Hypertrophic Cardiomyopathy
HCM comprises hyperplasia or thickening of individual muscle fibers of the heart. HCM in pet birds is usually secondary to pressure overload states (cardiomyopathy of overload), including arterial luminal stenosis due to advanced atherosclerosis and PH. As in mammals, the affected ventricle(s) ultimately undergoes concentric hypertrophy, in which the ventricular wall thickens with a corresponding decrease in chamber volume. Eventual ischemia of the hypertrophied myocardium results in fibrosis and increased collagen content, impairing both systolic and diastolic function. Analogous conditions in human and small animal medicine are ventricular outflow obstructions such as subvalvular aortic stenosis (SAS) and primary HCM, including the obstructive type characterized by systolic anterior motion (SAM) of the mitral valve. BB are utilized in the treatment of these conditions; their potential benefit is based on reduction of heart rate and myocardial oxygen consumption, as well as improved diastolic filling and coronary artery flow. However, in cats, evidence of their efficacy is scarce, with little to no indication that they improve survival in patients with CHF.
Anecdotally, BB can have merit for the treatment of HCM in birds. The author has utilized carvedilol, with or without an ACEI inhibitor, in a small number of psittacines with suspected atherosclerotic disease and concentric ventricular hypertrophy that had not yet progressed to failure. In each of these cases, there has been symptomatic improvement in the form of increased energy and activity level, appetite, and body weight. One of these cases was that of a 34-year-old, female yellow-naped Amazon parrot (Amazona auropalliata) that was treated for biventricular CHF secondary to advanced atherosclerotic disease. There was marked concentric hypertrophy of both ventricles, diastolic dysfunction, and sinus tachycardia. Following initial management with standard therapy (furosemide, spironolactone, enalapril, sildenafil, and pimobendan), clinical status deteriorated, and carvedilol was added to the treatment regime; pimobendan was discontinued. Following this change in the treatment protocol, rapid and marked clinical improvement was seen, after which the patient remained stable for an additional 7 months.
Systemic Hypertension
Systemic hypertension occurs in poultry species and can result in severe ventricular hypertrophy and CHF. Although not defined in psittacines, systemic hypertension probably is a disease entity in this group as well. In human and small animal medicine, BB are often used in conjunction with ACEI, CCB, and/or diuretics to reduce arterial blood pressure (BP). In humans, such treatment markedly reduces the risk of developing heart failure, and combined therapy with a BB and ACEI is recommended in cases of diastolic heart failure with concurrent hypertension. In cats, the CCB amlodipine is the treatment of choice for systemic hypertension; it has been shown to significantly reduce BP, and in one study, resolved secondary ventricular hypertrophy in 50% of subjects.
In companion birds, the application of BB, CCB, or other antihypertensive drugs for the treatment of systemic hypertension is complicated by the fact that there is no practical means to obtain accurate and repeatable arterial BP measurements in the clinical setting and no established definition of hypertension exists. Direct BP measurement, while accurate, requires invasive techniques; indirect BP measurements do not seem to correlate well with direct arterial BPs in birds. However, if in select cases, BP measurements are obtained and support a diagnosis of hypertension (direct systolic BP >240 mm Hg; indirect systolic BP consistently ≥270 mm Hg), combined treatment of an ACEI with a BB or a CCB may be considered.
Pulmonary Hypertension
Compared to mammals, birds are thought to have a greater propensity for developing PH and right-sided, rather than left-sided CHF owing to the morphology of the right AV valve, less deformable nucleated erythrocytes, and the rigid, non-distensible lungs which limit the ability of the blood capillaries to expand and accommodate greater blood flow. PH can result from pulmonary vascular disease (to include atherosclerosis), chronic pulmonary disease and/or hypoxia, congenital left-to-right shunts, or left-sided heart disease and failure. Secondary polycythemia, which develops as a consequence of chronic hypoxemia, can be a complicating factor in a number of disease conditions, including PH. Increased blood viscosity and larger and less deformable erythrocytes result in increased resistance to blood flow in the lung and other tissues.
Certainly, the known or hypothesized underlying cause(s) of PH should be addressed, if possible, but pulmonary vasodilators (sildenafil), CCB, pentoxifylline, and periodic phlebotomy may have symptomatic benefit in birds with a presumptive or definitive diagnosis of PH. Similarly, the inclusion of these drugs should be considered in the treatment of CHF patients with cor pulmonale.
Pulmonary Vasodilators
Sildenafil is a selective pulmonary vasodilator that acts by specifically inhibiting phosphodiesterase V (PDE5), an enzyme that degrades cyclic guanosine monophosphate (cGMP) in pulmonary vascular smooth muscle cells. The resulting increase in cGMP enhances nitric oxide (NO)-mediated pulmonary vasodilation, thereby reducing pulmonary vascular resistance and right ventricular afterload. The drug does not typically lower systemic arterial BP or alter heart rate. Its hypotensive effects may be increased upon concurrent use of α-adrenoceptor blockers, amlodipine, or other hypotensive drugs. In addition, its metabolism may be reduced by the administration of azole antifungals. In humans and dogs, sildenafil is an effective treatment for PH, and has been shown to improve quality of life and mitigate secondary polycythemia in dogs.
In birds, prolonged (>15 months) use of sildenafil (2.5–3 mg/kg PO q 8 h) has been described in a 25-year-old, male mealy Amazon parrot (Amazona farinosa) with suspected PH (based on clinical signs, secondary, absolute polycythemia, and consistent echocardiographic findings), in addition to therapeutic phlebotomy, and supplemental oxygen. In this bird, resolution and reappearance of the clinical signs (lethargy, anorexia, ataxia, tachypnea/dyspnea, and oxygen dependence) were found to coincide with changes to the dosing frequency (from 8–12 h). In addition, the author has treated an unknown-age, female rose-breasted cockatoo (Eolophus roseicapilla) with suspected PH, in which the clinical signs (lethargy and exercise intolerance) rapidly resolved with administration of sildenafil (2 mg/kg PO q 12 h) and enalapril (3 mg/kg PO q 12 h). Over a period of 1 year, doses of both drugs were gradually increased to 5 mg/kg PO q 12 h. Right ventricular hypertrophy decreased 6 months into treatment.
Other Treatment Options
Patients with suspected PH may also benefit from an ACEI, pimobendan, CCB, pentoxifylline, and therapeutic phlebotomy. Pentoxifylline, a methylxanthine derivative, increases the flexibility and deformability of erythrocytes and leukocytes and decreases blood viscosity in mammals. It thereby promotes blood flow through damaged or occluded microvasculature, and thus may have merit in avian patients with PH and secondary polycythemia and hyperviscosity syndrome.
Arrhythmias
Cardiac arrhythmias range from clinically insignificant to life-threatening, and/or terminal events. Clinical signs may be absent or include weakness, syncope, or sudden death. Arrhythmias rarely constitute a primary disease process; they can develop secondary to cardiac chamber dilatation, myocarditis, or cardiomyopathy of any cause, as well as toxicoses, nutritional deficiencies, electrolyte imbalances, and various anesthetic agents. They can be potentiated by catecholamine release as occurs with handling stress and painful conditions. Clinically significant cardiac arrhythmias likely represent the minority, but those that are symptomatic, causing hemodynamic instability, and complicating or precipitating heart failure warrant characterization and appropriate treatment. To date, reports of antiarrhythmic therapy in birds are extremely few.
Treatment of Tachyarrhythmias
Aside from digoxin, BB and CCB are utilized in small animal cardiology for the treatment of supraventricular tachyarrhythmias, including atrial fibrillation, in order to slow the ventricular response rate. Their use is generally contraindicated in patients with acute or decompensated CHF unless the arrhythmia is contributing to the condition such that conventional treatment alone has failed to stabilize the patient; however, even in this scenario, these drugs must be used with great caution, beginning at low dosages, with the aim of decreasing ventricular rate only marginally.
Sotalol (1–2 mg/kg PO q 12 h) was employed to control supraventricular tachycardia in a 19-year-old golden eagle (Aquila chrysaetos) with marked left atrial and ventricular dilatation, marked left ventricular systolic dysfunction, and stenosis of the right brachiocephalic trunk (most consistent with an atherosclerotic lesion). Sotalol was used in conjunction with isoxsuprine and pimobendan, resulting in resolution of the arrhythmia and restoration of normal chamber sizes and systolic function. The patient had remained in stable condition for 15 months at the time of case report publication.
Lidocaine is a parenteral antiarrhythmic agent used to control life-threatening ventricular tachyarrhythmias. At usual doses, there is minimal effect on the cardiac conduction system or on myocardial contractility. To the author’s knowledge, there are no reports describing its use for the treatment of tachyarrhythmias in avian species, but its pharmacokinetics and cardiovascular effects have been evaluated during experimental studies.
Treatment of Bradyarrhythmias
Bradyarrhythmias, and in particular, second- and third-degree AV blocks, have been noted in birds with cardiac disease. Escape beats and escape rhythms may be seen with severe bradyarrhythmias; they are of ectopic origin and perform an essential salvage function by preventing asystole at low heart rates. QRS morphology of ventricular escape beats may be abnormal (wide and bizarre), but these should not be confused with premature beats (additional beats added to already normal or rapid heart rate), because in the case of escape beats, antiarrhythmic therapy is contraindicated.
Antimuscarinic agents, including atropine and glycopyrrolate, can be used for both the diagnosis and treatment of bradycardias related to increased vagal tone, including sinoatrial (SA) arrest and first- and second-degree AV block. They are also used as antidotes for organophosphate and carbamate intoxication. These drugs are contraindicated in patients with tachycardia or tachyarrhythmias and must be used cautiously in patients with heart failure. Since the activity of atropine and glycopyrrolate is short-lived, they are mainly used during the treatment of bradycardia during anesthesia. For long-term use, propantheline, an oral antimuscarinic agent, has been used to normalize heart rate and rhythm in a 30-year-old Moluccan cockatoo (Cacatua moluccensis) with second-degree AV block (Mobitz type 2).
Supportive Care and Husbandry Considerations
Along with medical management of CHF, it is often necessary to address concurrent problems and meet specific supportive needs. Patients may be presented in a severely debilitated state, with cachexia, dehydration, secondary renal dysfunction, and injuries. In-patient supportive care measures may include oxygen supplementation, nutritional support, fluid therapy (though parenteral fluid administration must be carefully questioned), and analgesia. Once the patient has been stabilized and discharged, longer-term management strategies should also incorporate exercise restriction, housing modifications, and dietary and lifestyle changes.
Supportive Care
General supportive principles apply to the avian heart failure patient, namely rest, minimizing stress with judicious, limited handling and restraint, and provision of supplemental oxygen when appropriate. Patients are typically dyspneic due to pulmonary edema, intracoelomic air sac compression by ascitic fluid, and/or pericardial effusion. Oxygen supplementation is indicated for patients with pulmonary edema, whereas physical fluid removal is more efficacious to stabilize those with air sac compression and cardiac tamponade.
Coelomocentesis will rapidly relieve air sac compression in cases of ascites. It is justified as a short-term stabilization strategy in patients with severe respiratory compromise. When large fluid volumes are present, the procedure can be performed relatively safely with (ideally) or without ultrasound guidance. Small fluid volumes will usually resolve with medical management alone without the need for physical fluid removal. Although coelomocentesis can be performed periodically over the longer term, it should not be substituted for pharmacologic management.
Fluid Therapy Challenges
Maintaining the delicate balance between the management of hypervolemia and concurrent dehydration and renal dysfunction is a profound clinical challenge, requiring close monitoring for changes in clinical status and adjustment of the treatment plan accordingly. Fluid therapy is generally not indicated in the treatment of CHF where a primary, immediate goal is the reduction of fluid overload. Initial treatment of acute and decompensated CHF frequently results in some degree of dehydration and pre-renal azotemia, but these abnormalities can resolve over a few days without fluid therapy once food and water intake have normalized.
In cases with persistent, severe azotemia, it may be necessary to administer small volumes of parenteral fluids, but patients for which hemodynamic stability cannot be achieved without severe renal compromise have a poor prognosis. Subcutaneous fluid absorption may fail in cases of right-sided CHF.
Exercise Restriction and Housing
Weakness and ataxia may limit patient mobility and access to food and water, and predispose to falls. This necessitates housing modifications designed to limit exertion and allow easy, immediate access to food and water. As even debilitated birds will often persist in trying to climb or perch, enclosures that prevent or limit this activity are ideal. Incubators, aquarium set-ups, or plastic or acrylic bins with a soft substrate serve this purpose well and permit visual monitoring. Depending on patient strength and stability, a low, secure and stable perch can be provided (such as a rope perch or rolled towel situated on the bottom of the enclosure). Once the patient regains strength and exercise tolerance, housing can be adjusted to allow greater activity (as in a small cage or crate, furnished with low perches and readily accessible dishes); some patients will ultimately be able to return to a traditional cage with no specific exercise restrictions.
Diet and Lifestyle
Longer-term husbandry considerations, including dietary changes (entailing optimum nutrition and sodium restriction) and lifestyle changes, mirror those discussed for atherosclerosis; however, dietary changes should not be made until the patient is well-stabilized. Given that CHF often arises secondary to atherosclerotic disease in psittacine birds, preventive considerations may be applicable to both conditions.
Other
Considering that most patients will require long-term (if not life-long) medical management, operant learning methods and food vehicles should be employed to facilitate low-stress medication administration.
Pericardial Effusion and Cardiac Tamponade
Pericardial effusion is characterized by an inappropriate accumulation of fluid within the pericardial sac. Several causes have been reported, though in some cases, an underlying cause cannot be identified, and the condition is ruled idiopathic. Severe pericardial effusion or restrictive pericarditis can compress the heart, resulting in impaired ventricular filling (diastolic dysfunction), and subsequent decreases in stroke volume and cardiac output. This condition, which can become life-threatening, is referred to as cardiac tamponade. Since the intramural pressure of the thinner-walled right ventricle is overcome more rapidly than that of the left, cardiac tamponade results more quickly in right-sided CHF than in left-sided failure.
Treatment for pericardial effusion and cardiac tamponade is based first on the removal of the fluid, and second on the treatment of the underlying etiology of fluid accumulation. Fluid removal can be accomplished either by ultrasound-guided or endoscopic pericardiocentesis, or by endoscopic or surgical fenestration of the pericardium.
Although diuretics are generally contraindicated in cardiac tamponade because they decrease the preload necessary to maintain ventricular filling pressure and cardiac output, furosemide with or without an ACEI may be useful to reduce pericardial fluid of low volume related to CHF in birds.
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