2016 FALL: Intractable Heart Failure | Coughing Canine | Congestive Heart Failure | Pimobendan for Cats? | Heart Murmurs | Continuing Education
Intractable Heart Failure
Canine patients presenting with refractory or intractable congestive heart failure (CHF) pose a therapeutic challenge. Commonly, these patients have mitral valve disease (MVD) or dilated cardiomyopathy (DCM). They present with ongoing pulmonary edema despite standard medical management with furosemide, an ACE inhibitor, and pimobendan. Consider these recommendations in these patients, with CHF secondary to MVD or DCM in dogs. Always rule out owner non-compliance first.
How does it develop?
Patients develop intractable CHF for a variety of reasons:
- Presence of a concurrent systemic disease exacerbating CHF: renal failure, hyperadrenocorticism, hypothyroidism, hyperthyroidism (including iatrogenic), systemic hypertension, systemic inflammation, neoplasia, anemia, pulmonary thromboembolism
- Onset of arrhythmias:
- Tachyarrhythmias: atrial fibrillation, frequent ventricular premature contractions (VPCs) or ventricular tachycardia
- Bradyarrhythmias: third degree heart block
- Rupture of chordae tendineae in MVD
- Left atrial tear in MVD
How do you diagnose it?
Careful physical examination, appropriate laboratory tests (CBC, biochemistry, urinalysis, endocrine tests), blood pressure measurement, electrocardiography (ECG), thoracic radiography, and potentially echocardiography. Examine radiographs carefully for the presence of primary respiratory disease that mimics CHF. Any potential underlying cause for exacerbation of CHF should be treated/managed directly.
What are the treatment options?
Optimization of doses of standard medication
Before additional therapies for intractable heart failure are considered, standard therapies should be optimized. An optimal ACE-inhibitor dose, whether enalapril or benazepril, is generally 0.5 mg/kg BID, providing renal parameters are normal. Pimobendan is typically dosed at 0.25 to 0.35 mg/kg BID. While furosemide doses are typically in the range of 2 – 3mg/kg BID-TID PO, doses as high as 5 mg/kg TID are sometimes required. Careful monitoring of volume status, renal function and electrolytes is imperative, as always. Optimal diuretic response to furosemide may actually be achieved by increasing the frequency of dosing (e.g. from BID to TID) with or without increasing the total daily dose, as it has a generally short duration of action that has no doubt dissipated by the time the next dose is given in BID dosing.
Additional preload reduction
As described above, furosemide dose and frequency of administration may be gradually increased, with careful monitoring of volume status, renal function and electrolytes. Doses higher than 5 mg/kg TID PO (15 mg/kg total daily dose) are unlikely to yield significant gains. In fact, tolerance to loop diuretics develops in the form of hypertrophy and increased resorptive capacity of renal tubular segments distal to the loop of Henle. For this reason, the addition of a second diuretic with a site of action distal to the loop of Henle may produce a synergistic and highly efficacious diuretic response. Spironolactone is an aldosterone antagonist with potassium-sparing diuretic action in the distal and collecting tubules. Thus it may also result in synergistic diuresis, albeit much less than a thiazide (see below). Doses are typically 1-2 mg/kg BID PO, and the dose of furosemide is not necessarily reduced in the face of its initiation. Additional diuretics for refractory congestive heart failure include torsemide and hydrochlorothiazide. Torsemide is a loop diuretic that is 10 times more potent than furosemide and blocks aldosterone as well. Hydrochlorothiazide is a thiazide diuretic acting in the distal tubule that may be added to furosemide therapy. Renal function and electrolytes must be monitored closely (and within a few days) as the risk of development of renal insufficiency or electrolyte disturbances is significant. Also contributing to diuretic resistance in CHF patients is the reduction in delivery of drug to its site of action secondary to reduced cardiac output. While increased doses are one way to try to overcome this issue, administration of diuretic parenterally is another means of increasing efficacy. Temporary administration of IV boluses of furosemide or use of a short-term constant rate infusion (see below) is sometimes effective in stabilizing refractory CHF patients. Long-term, one or more daily doses (unchanged dose) of furosemide can be given subcutaneously, instead of orally.
Venodilation promotes redistribution of blood volume from the central circulation (heart and lungs) to the systemic venous circulation, thereby reducing left atrial pressure and pulmonary edema. The nitrates are commonly used venodilators in addition to ACE-inhibitors and pimobendan, though evidence of efficacy and appropriate dosing is lacking in canines, particularly for nitroglycerin ointment.
Additional afterload reduction
In patients with acceptable blood pressure (systolic BP > 90 mmHg), afterload reduction with additional arterial vasodilators may be effective in increasing forward flow, reducing regurgitant flow, and decreasing wall stress, ultimately resulting in decreased pulmonary edema. ACE-inhibitors and pimobendan both have arterial vasodilating properties, the latter likely more potent than the former. Amlodipine is a dihydropyridine calcium channel blocker with action primarily on vascular smooth muscle. It has a long half-life (30 hours) and thus a slow onset of action. It is initiated at 0.05-0.1 mg/kg once daily PO, and may be up-titrated to 0.2 mg/kg once daily as long as blood pressure is monitored (after 5-7 days) and remains > 90 mmHg systolic. Hydralazine is another potent vasodilator with an unknown mechanism of action and much more rapid onset of action. It is initiated at 0.5 mg/kg BID PO and may be up-titrated to 1.5 mg/kg BID with careful and more frequent monitoring of blood pressure. Frequent side effects include hypotension, tachycardia and gastrointestinal signs. Periodic monitoring of renal function is necessary with either vasodilator.
Addition of, or increase in, positive inotropic therapy
The rationale for the use of positive inotropes is perhaps most apparent in DCM, where systolic dysfunction is the primary defect and thus improvement of such seems desirable. In CVD, systolic dysfunction is often a component of late stage and refractory disease, and reduction in regurgitant orifice may also be achieved with positive inotropes.
On occasion, a higher dose (label dose is up to 0.35 mg/kg BID) or frequency (can be given TID) of pimobendan may be used in patients that are experiencing refractory pulmonary edema despite high doses of diuretics and with concurrent renal insufficiency.
Thank you to Sarah Achen, DVM, DACVIM-Cardiology, from BluePearl in Michigan.
The Diagnostic Dilemma of the Coughing Canine
The coughing dog can be a diagnostic dilemma. The presence of a cough can suggest pulmonary and/or heart disease. Some dogs and cats will be afflicted with both.
Coughing can be caused by compression of the mainstem bronchi from an enlarged left atrium.
Because the pet’s treatment and prognosis will vary between pulmonary and cardiac causes for coughing, it is important to differentiate the two potential sources. (Heartworm disease may also produce a cough, but diagnosis of heartworm disease will not be discussed in this article.) The physical exam can provide important clues for differentiating cardiac and pulmonary causes for coughing.
Causes for a cardiac cough include 1) compression of the left mainstem bronchus from an enlarged left atrium, and 2) early pulmonary edema. Both scenarios require an elevation in left atrial pressure. This is most commonly caused by volume overload associated with the presence of mitral valve regurgitation. These dogs will have a mitral valve insufficiency associated murmur (systolic murmur with point of maximal intensity at the left apex). Meanwhile, diminished forward blood flow secondary to mitral valve regurgitation typically causes an increased heart rate. Therefore, if the coughing patient you are examining has a normal or slow heart rate and lacks a heart murmur, heart disease is unlikely to be the cause of the cough. The presence of a heart murmur, however, is not enough to conclude the cough is caused by a heart condition.
Congestive Heart Failure
Congestive heart failure (CHF) is a clinical syndrome commonly encountered in small animal practice. Although there are a multitude of underlying cardiac diseases that can predispose patients to heart failure, the development of CHF represents a final common pathway resulting from insufficient cardiac function. The primary mechanism for the development of CHF is a cascade of neurohormonal responses involving the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS). The activation of these systems promotes sodium and water retention, an increase in sympathetic tone, and causes peripheral vasoconstriction.
The standard therapy for heart failure over the past decade has involved the use of diuretics (furosemide) and an ACE inhibitor (enalapril, benazepril, lisinopril). Additional medications, including digoxin and other diuretics (spironolactone, torsemide, thiazides) are also commonly used in the treatment of heart failure. Antiarrhythmic agents, such as beta blockers and calcium channel blockers (diltiazem), may also be indicated if cardiac arrhythmias occur in conjunction with heart failure.
Pimobendan (Vetmedin®) is a drug that increases cardiac contractility by inhibiting phosphodiesterase, as well as sensitizing cardiac myofilaments to calcium. Pimobendan is termed an inodilator because of its combined inotropic and vasodilatory properties. This medication was initially used in Europe and Canada, and is approved in the United States for use in dogs with CHF. The veterinary experience with Vetmedin has been overwhelmingly positive, making Vetmedin an important drug in the treatment of CHF.
It is important to recognize that while many drugs are available for the treatment of CHF, not all drugs are required in every case. The ability to accurately manage patients requires a thorough cardiac evaluation, including chest radiographs, echocardiography, electrocardiography (ECG), blood pressure evaluation and biochemical analysis. A comprehensive cardiac evaluation facilitates the effective management of disease and enables specific identification of the underlying etiology. Since the clinical signs of heart disease mimic those of respiratory disease, it is prudent to obtain an accurate evaluation. The clinical challenge of correctly diagnosing patients presenting for signs of coughing or respiratory difficulty underscores the importance of thorough cardiac evaluation prior to initiation of heart failure therapy.
We would like to thank our colleague from BluePearl in Florida, Alan Spier, DVM, DACVIM-Cardiology, for allowing us to use this article for Companion.
Pimobendan- What About Cats?
Pimobendan is the latest and greatest cardiac medication added to our arsenal for treating mitral valve insufficiency and dilatative cardiomyopathy in dogs. Pimobendan acts as a positive inotrope in dogs, improving ventricular contractile function and cardiac output. It also has balanced vasodilatory effects improving blood flow to and away from the heart. Studies have demonstrated pimobendan to improve the clinical signs and prolong the survival times of dogs with congestive heart failure.
It’s only natural to wonder whether pimobendan will work in cats. Although not presently approved for use in cats with heart disease, numerous studies have shown that pimobendan is safe for use in cats (MacGregor JVetCard; Hambrook, JFelMedSurg) . Retrospective studies have shown that cats with CHF secondary to HCM and DCM that received pimobendan had a longer median survival time than cats that did not receive pimobendan; 626 days versus 103 days (Reina-Doreste, JAVMA) and 49 days versus 12 days (Hambrook, JFelMedSurg), respectively.
Although pimobendan appears to be well tolerated in most cats, its use is contraindicated with left ventricular outflow tract obstruction due to the concern for worsening of the obstruction and possibility for resulting hypotension. Ideally an echocardiogram would be performed prior to starting therapy with pimobendan in cats to ensure there is no evidence of outflow tract obstruction.
What’s That Sound? Approaching Heart Murmurs in Dogs and Cats
Unexpectedly finding a heart murmur during a routine wellness examination is common. Determining what, if any, additional diagnostics are warranted can be difficult, and many owners will want to know possible causes before they decide to visit a cardiologist. Recommendations vary on a case-by-case basis, but generally considering the patient’s signalment, clinical signs and the client’s goals can help recognize which cases are most likely to benefit from advanced diagnostics including echocardiography.
Systolic murmur in a puppy
Benign or “innocent” murmurs are not uncommon in puppies. These murmurs are generally soft (I-II/VI), systolic, loudest at the left base and typically resolve by 4-6 months of age. Importantly, these murmurs are not associated with clinical signs. It is reasonable in an otherwise healthy puppy with no familial history of heart disease and a quiet left basilar murmur to recommend waiting and rechecking when they are older. Offering echocardiography at the time of initially hearing the murmur is a good idea as some owners will want to be more proactive and pursue imaging sooner. For purebred puppies about to be sold or those with heart disease documented in their lineage, echocardiography is reasonable when the murmur is first heard.
Puppies with murmurs and clinical signs of heart disease including lethargy, weakness, collapse or breathing difficulties should be referred for an echocardiogram. Additionally, puppies with arrhythmias, abnormal heart sounds, right-sided or apical murmurs, moderate to loud murmurs especially associated with a palpable precordial thrill (grade III-VI), and those with continuous murmurs should all receive recommendation for echocardiography as soon as possible.
Systolic murmur in an adult small breed dog
The most common murmur in a small breed middle-aged to older dog is chronic degenerative valvular disease causing mitral and/or tricuspid regurgitation. This classically leads to a systolic left (mitral) and/or right (tricuspid) apical murmur. With moderate to severe degenerative valvular disease the murmurs are typically at least moderate (grade III/VI or above). Since the risk of congestive heart failure and the associated clinical signs of tachypnea at rest, coughing and dyspnea correlates with cardiac (and specifically left atrial) size, thoracic radiographs are a reasonable initial diagnostic in an adult small breed dog with a systolic apical murmur. Generally, if the heart size is normal (VHS < 10.5 in most breeds) and the patient is asymptomatic, monitoring with thoracic radiographs every 12 months is recommended. With radiographic cardiomegaly, rechecking every 6 months is indicated or sooner if clinical signs develop. An initial echocardiogram to confirm the underlying disease type is reasonable even when the heart size is normal but should certainly be considered when there is radiographic evidence of cardiomegaly. Benefits of echocardiography not apparent on radiographs include assessing for pulmonary hypertension, systolic function and additional flow abnormalities. Small breed adult dogs with murmurs that are atypical in location or accompanied by arrhythmias or clinical signs should always be offered echocardiography and consultation with a specialist.
Systolic murmur in an adult large breed dog
Large breed dogs can also be affected by degenerative mitral and tricuspid valve disease, but dilated cardiomyopathy is considerably more common in these breeds than in small breeds and can be difficult to diagnose without echocardiography. Large breed dogs with dilated cardiomyopathy can have no audible murmur or a very low-grade murmur despite having severe cardiac disease. For this reason, any large dog with clinical signs suggestive of cardiac disease, radiographic evidence of cardiomegaly, or any cardiac murmur should be offered echocardiography.
Diastolic murmurs in dogs
Diastolic murmurs are uncommon in small animals and auscultation of these murmurs always warrants referral to a cardiologist for additional imaging. These are typically associated with severe aortic regurgitation such as that seen with bacterial endocarditis. Other aortic valve abnormalities or, in theory, severe pulmonic insufficiency with pulmonary hypertension and mitral/tricuspid stenosis could also cause diastolic murmurs.
Thickened left ventricular wall consistent with severe hypertrophic cardiomyopathy noted on echocardiography in a cat with a new heart murmur.
Benign murmurs are very common in cats and are often related to relatively rapid blood flow through the right ventricle (called dynamic right ventricular outflow tract obstruction). These murmurs are systolic in timing and can be heard on either the right or left parasternal areas. They typically are mild to moderate in intensity (grade I-III/VI) and may vary with heart rate or be intermittently audible. Unfortunately, the only way to differentiate a benign feline murmur from a pathologic murmur associated with cardiomyopathy or valvular dysplasia is echocardiography. Radiographs can offer support for underlying heart disease if there is clear cardiomegaly (VHS >8, “valentine” shape) though normal thoracic radiographs do not rule out the possibility of heart disease. It is reasonable, therefore, to offer owners of feline patients referral for echocardiography at the time a murmur is ausculted. This recommendation is especially important if the patient requires general anesthesia for surgery or dental cleaning. Cats with loud murmurs (> grade IV/VI), arrhythmias, or clinical signs should always be offered echocardiography. Cats can also have cardiomyopathy without an audible murmur so some patients, especially those with a family history of cardiac disease or those intended for breeding, may require an echocardiogram despite not having a murmur.
A recent summary released in the Journal of Small Animal Practice (E.Coté et al. Incidentally detected heart murmurs in dogs and cats: executive summary 2015) is available online and provides more information and frequently asked questions regarding incidental murmurs in small animal patients.
We would like to thank our colleague from BluePearl in Georgia, Danielle Laughlin, DVM, DACVIM-Cardiology, for allowing us to use this article for Companion.
FROM THE MEDICAL DIRECTOR
Medical Director’s Notes
We at BluePearl hope that everyone had a wonderful summer. As we head into the fall, we have some exciting announcements to share with you.
Please join us in welcoming Dr. Kursten Pierce to the BluePearl cardiology team in Waltham. Dr. Pierce comes to BluePearl experienced in echocardiograms (small, large and exotic animals) and interventional procedures after completing a cardiology residency at Tufts University. Her clinical interests include long-term management of chronic valvular disease and dilated cardiomyopathy; the use of cardiac biomarkers, such as NT- proBNP, to monitor disease progression and guide therapies; and finding ways for early detection of feline heart disease.
We are extremely excited to add Dr. Pierce to our growing team as we continue to broaden the services we offer to the primary care veterinary community. This issue of the Companion is focused on cardiology, so please reach out to Dr. Pierce with any questions. She is available for appointments and phone consults Monday-Thursday.
We have also expanded our diagnostic imaging services to include outpatient ultrasounds on Saturdays. Radiologist, Marcia Whitely, and Dr. Maura Carney, from our internal medicine service, will each be available two Saturdays every month. We hope that our expanded weekend service will help to better serve you and your clients’ needs.
We stand by our five-point commitment to you:
- We provide remarkable care and service to you and your clients.
- We operate strictly by referral.
- We will call and mail you a written report for every referral.
- We do NOT provide routine, general, or prophylactic care.
- We are happy to consult on cases with you whenever you call.
Kristina DePaula, DVM, DACVECC
BluePearl is strongly committed to the veterinary community. One of the ways we demonstrate this commitment is through our continuing education program, which is subsidized in part by our Partners in Education.
All BluePearl lectures are free and include a light dinner. Please RSVP to Jodi Melvin at 781.684.8387 or firstname.lastname@example.org.
|Nov 9||Dinner 6:00PM|
|Doctor||Pet Puzzlers: Interactive Case Review of Your Puzzling Cases|
Leslie Schwarz, DVM, DACVR
Bari Spielman, DVM, DACVIM
|BluePearl Waltham||2 hours|