When owners present their pets with congestive heart failure, they want to know:
The answers to these questions begin with an accurate diagnosis. Congestive heart failure is not a diagnosis, just like diarrhea is not a diagnosis - they are but clinical signs. The prognosis and response to therapy for both quality of life and length of life depend on an accurate diagnosis; just as with diarrhea the prognosis and response to therapy depend on the diagnosis of the cause of the diarrhea. Thus, we need to determine the cause of congestive heart failure.
The ideal approach to improving quality of life and survival is to repair the primary abnormality such as make the heart stronger if weak, or fill better if indistensible, or repair the leak if mitral or aortic valve insufficiency is present. Since we cannot usually accomplish these goals, we rely on two approaches to management:
The subsequent sections will address specific efforts to identify therapies that attempt to improve the performance of the heart and circulatory system.
I wish to address the issue of therapy to modify vascular volume. The management of most cases of congestive heart failure, regardless of cause, involves an attempt to plot a management path between excessive fluid in the vasculature and reduced fluid in the vasculature. Excessive fluid in the vasculature, on the positive side, promotes an increase in cardiac output with enhancement of renal, GI, and skeletal muscle function. On the negative side, excessive fluid in the vasculature promotes pulmonary congestion with respiratory difficulties. Reduced fluid in the vasculature has a positive impact when it promotes a reduction in pulmonary congestion and the accompanying respiratory problems. However, reduced fluid in the vasculature also causes a reduction in cardiac output that will result in reduced renal, GI, and skeletal muscle function. Thus our therapeutic path attempts to find the ideal level of vascular fluid that falls between our two objectives, to promote an increase in cardiac output and to reduce pulmonary vascular volume. To remain on this path one needs to frequently "tweak" the level of medication. Our approach to these patients is to assess pulmonary congestion, via history, auscultation, and chest radiographs, and renal function and electrolyte status, especially potassium, with every examination. Our goal is to find the least dose of total diuretic that will maintain ease of breathing. This least dose will usually not result in completely clearing the lungs of congestion but should maximize the cardiac output. To use more diuretic than that required to maintain ease of breathing, such as to "really" clear the lungs, will cause an unnecessary and potentially harmful reduction of renal function.
Response to Shock:
Comment: This response to a reduction in preload serves to raise BP. Note that the duration of shock is generally measured in hours. Shock is a disorder that is not intended to last days, months, and years.
Response to Heart Failure: (BP falls as with shock but is persistently reduced for days to years, thus the shock response is active for days to years).
Comment: In the setting of heart failure these responses serve to exacerbate heart failure and are responsible for the relentless progression of the heart failure state. In people the only therapies (except for cardiac transplantation) that have been demonstrated to increase survival are therapies that blunt the "Shock" response. Specifically only beta blockers, ACE inhibitors, and aldosterone receptor blockers have increased survival.
Some of these classes are overlapping. It is important to consider the class of drug therapy most beneficial with each pathophysiologic state. Do not memorize the present day drugs but consider only the classes of drugs and then review the most current veterinary literature (i.e. Current Veterinary Therapy XXII if appropriate) and find the best representative drug of that class at the time.
The disadvantages to diuretic therapy are:
Comment: The combined use of diuretics can have a profound effect on diuresis (such as use of furosemide and hydrochlorothiazide). Reduced doses of each diuretic are required when starting the combined drugs. The doses can be titrated on a daily basis, particularly while monitoring renal function, which can fall dramatically in a short period of time.
Diuretics are an important class of drug in the management of heart failure. However they can cause considerable debilitation. One must strive to find the least dose required to achieve your goal. Frequent monitoring is required to ensure the least dose is achieved.
Advantages - rapidly reduces pulmonary edema. Also decreases myocardial oxygen consumption by reducing ventricular volume.
Disadvantages - as preload is reduced, stroke volume falls. However, because the cardiac function curve for the failing heart is relatively flat (shifted downward and to the right), significant reductions in preload may produce only mild reductions in stroke volume. A marked reduction in preload with the subsequent reduction in stroke volume can cause severe hypotension, particularly in patients with an already reduced stroke volume.
Common venodilators are:
Comment: Vasodilators are classified as:
While classified as so-called pure veno- or arterial vasodilators, all of these agents have some mixed vasodilator features while affecting primarily the venous or arterial tree, respectively.
Comment: In people, tolerance develops to sustained nitrate therapy. Presumably, this may also occur in animals. To minimize this effect, use pulsed therapy with drug use for 12 hours, then none for the next 12 hours, then start again for 12 hours, and so on.
Comment: Whenever vasodilator therapy is added to diuretic therapy the potential for hypotension is greatly increased.
Advantages: Reduce afterload causing an increase in stroke volume, decrease in MVO2, and decrease in preload
Disadvantages: May significantly reduce blood pressure causing hypotension; may cause a reflex tachycardia
Indications: Symptomatic chronic mitral valve insufficiency (CMVI) or dilated cardiomyopathy (DCM), systemic hypertension.
Contraindicated in: Valvular stenosis, hypertrophic cardiomyopathy, cardiac tamponade, hypotension
Common arterial vasodilators:
Note: Prazosin and ACE inhibitors are more balanced than pure arterial vasodilators.
Like all arterial vasodilators these drugs can induce arterial hypotension. Renal arterial hypotension may be the most common consequence causing a reduction in GFR (BUN/creatinine become elevated). ACE inhibitors can cause cough in people. Cough is rare in domestic animals.
Indications: Symptomatic CMVI, symptomatic or asymptomatic DCM, systemic hypertension, CHF due to hypertrophic cardiomyopathy
Contraindicated in: valvular stenosis, cardiac tamponade, hypotension
Comment: Of the ACE inhibitors, enalapril, benazepril and imidapril have been approved to treat dogs with heart failure in Canada. Only enalapril is approved in the United States. Although the manufacturer for benazepril recommends once daily dosing, we believe a dose of 0.5 mg/kg BID is better. In addition, we dose enalapril at 0.5 mg/kg BID for our patients with heart failure.
Comment: Benazepril undergoes less renal excretion than enalapril. In the setting of renal insufficiency, a common by-product of heart failure, less of the active compound will accumulate in the blood stream. At this time it is unclear that this represents a real advantage for benazepril.
Combined (mixed) vasodilators:
- A large dosage is used.
- A gradual increase in dosage to maintenance levels is not followed.
- Combined with diuretics (vasodilator dosage must be monitored more carefully).
- Patient is volume depleted.
Indications: pulmonary edema, pleural or abdominal effusions, systemic hypertension
Contraindications: valvular stenosis, cardiac tamponade, hypotension
Clearly the best method to assess hypotension is to measure the arterial blood pressure. In that blood pressure is not always obtainable in small animals, we also resort to measuring the consequences of arterial hypotension. This involves assessing renal function (urea, creatinine) and attempting to determine if there is any reduction in renal function.
Thus, when potent vasodilators such as hydralazine or amlodipine are used, either alone or in combination with other vasodilators or diuretics, urea and creatinine should be monitored 5 to 10 days after drug initiation, and then periodically thereafter, particularly prior to an increase in the dosage of the vasodilator or the diuretic.
If urea and creatinine are elevated, the diuretic dose may be reduced first, as opposed to the ACE inhibitor or vasodilator dose. Recheck renal function in 5 days.
Moderate to severe hypotension will require intravenous fluid therapy.
Mild hypotension may be treated by merely reducing the dose of the diuretic agent and augmenting oral water intake.
Advantages: Increase in contractility shifts the cardiac function curve upward and to the left causing an increase in stroke volume for the same level of preload.
Indications: CHF secondary to CMVI (particularly when systolic dysfunction is present) or DCM
Contraindicated in: hypertrophic cardiomyopathy, valvular stenosis, cardiac tamponade
Modes of inducing positive inotropy:
Comments: Pimobendan is the only positive inotrope has been evaluated clinically in the dog. Pimobendan is approved for the treatment of congestive heart failure due to dilated cardiomyopathy and chronic mitral valve insufficiency in the dog.
2. Digitalis (digoxin)
ECG is not useful to detect digitalis intoxication
Comment: There has been considerable controversy as to the efficacy of digitalis in the setting of heart failure in patients with a normal sinus rhythm. Emerging evidence suggests that digoxin may have a beneficial effect not as a result of its modest positive inotropic properties but digoxin may reduce the enhanced sympathetic activity characteristic of heart failure. In that this enhanced sympathetic activity may contribute to the vicious cycle of heart failure begets more heart failure, digoxin may be beneficial.
Comment: Dobutamine has a role only in the acute management of severe heart failure due to systolic dysfunction. A three-day infusion of dobutamine has been very useful in people to revert cases of refractory heart failure with pulmonary edema into a state of stable heart failure.
Comments: All positive inotropes (both oral catecholamines and phosphodiesterase inhibitors) have failed to improve survival in people with chronic heart failure due to systolic dysfunction. In fact, this group of agents has reduced survival in these patients. Dogs may be quite different from people in their potential to respond to positive inotropes. Only pimobendan has been shown to improve survival and quality of life for dogs with CHF.
These agents are also potent negative chronotropes. They may mediate most of their benefit via their negative chronotropic properties.
Contraindications: Active and significant pulmonary edema, hypotension, bradycardia
1. COVE Trial (COVE Study Group. JVIM 1995;9(4):243-252)
2. LIVE Trial (LIVE Study Group. JAVMA 1998;213(11):1573-1577)
3. BENCH Trial (BENCH Study Group. J Vet Cardiol 1999;1(1):7-18)
1. The Fuentes Study (Fuentes et al: JVIM 2002;16(3):255-261)
2. University of Guelph Pimobendan in DCM Trial (O'Grady MR, Minors SL, O'Sullivan ML and Horne R. JVIM 2008:22:897-904).
3. QUEST Trial (Haggstrom J, Boswood A, O'Grady M, et al for the Quest Investigators JVIM 2008;22(5):1124-35)
Treating pre-clinical heart disease due to CMVI or DCM in dogs (absence of clinical signs):
The goal of therapy at this stage of heart disease is not to improve clinical signs as none exist. The goal of therapy is to delay the inevitable progress to overt heart failure (onset of clinical signs).
Treatment of symptom-free (free of clinical signs) CMVI:
Two studies investigated the role of ACE inhibitors to delay the progression of CMVI to the onset of clinical signs of heart failure:
1. SVEP Trial (Kvart et al: JVIM 2002;16:80-88)
2. VETPROOF Trial: Atkins et al: JAVMA 2007;231(7):1061-1069
Treatment of symptom-free (free of clinical signs) DCM:
One published study from the University of Guelph has investigated the role of ACE-inhibitors to delay the progression of DCM to the onset of clinical signs of heart failure:
1. Benazepril in Occult Doberman DCM (O'Grady MR, O'Sullivan ML, Minors SL, Horne R. JVIM 2009;23:977-983)
In addition to establishing a diagnosis, there are other factors to consider when selecting a therapeutic plan:
The goals of therapy are to relieve the severe pulmonary edema. One requires at least a presumptive diagnosis as to the cause of pulmonary edema in order to develop a therapeutic plan. For patients with pulmonary edema due to systolic dysfunction, pulmonary edema is reduced by:
What about oral therapies? There is no place for oral therapy in these cases. As they are anorectic, they likely have little to no gastric motility so that the medication may just sit in the stomach. In addition, intestinal absorption is likely markedly reduced as blood is usually shunted away from the bowel.
What about intravenous fluids? In general, no intravenous fluids should be used. Fluids are only used if they are required as a vehicle to administer drugs requiring constant rate infusion such as sodium nitroprusside, dobutamine, or antiarrhythmic drugs. In these situations, only use 25% of the maintenance fluid rate and use fluids low in sodium such as 5% dextrose in water or half strength saline and dextrose. Also monitor that the combined fluid of all CRIs does not inadvertently result in further fluid overload.
What about inducing azotemia? Expect that some degree of azotemia will develop since aggressive volume depletion is sometimes necessary to relieve severe life threatening pulmonary edema. In two to three days after the onset of therapy, we may be required to provide fluid support for renal function at which time cardiovascular status should be substantively improved and the patient should be able to handle the fluid load. In addition, as cardiac performance improves the renal blood flow will improve.
So how would the authors treat this patient with systolic dysfunction and fulminant pulmonary edema? We must consider whether we have the ability to provide continuous monitoring. We recommend attempting to use a facility that has continuous monitoring.
The goals of therapy are:
Usually the cause of heart failure cannot be identified as in dilated cardiomyopathy or cannot be altered as in the case of chronic mitral valve disease.
However, it can be very productive to identify and arrest any precipitating causes of heart failure such as:
In addition to addressing the precipitating causes of heart failure, we want to introduce therapies that can extend both the quality and length of life. Today, only the ACE inhibitors and pimobendan have been demonstrated to extend survival for dogs.
So how would the authors treat this patient?
Management of congestive heart failure involves controlling vascular volume by finding a balance between meeting renal blood flow needs through enhancing vascular volume (preload) and reducing pulmonary edema by reducing vascular volume (preload).
Surveillance: The following should be monitored at least once weekly initially:
Recent work in the Doberman shows us that dogs with left ventricular enlargement and reduced contractility but free of symptoms of heart failure (occult dilated cardiomyopathy) benefited from the use of ACE inhibitors. ACE inhibitors delayed the onset of overt signs of heart failure (see above). Other breeds of dogs with occult dilated cardiomyopathy should also benefit from the early use of ACE inhibitors.
However, the situation in dogs with chronic mitral valve insufficiency (such as small breed dogs with a mitral valve murmur but free of symptoms) and in the absence of heart failure is unclear. Only ACE inhibitors have been assessed in this setting in naturally-occurring disease, and they have failed to delay the onset of congestive heart failure in dogs with mitral valve insufficiency and no clinical signs. Work with experimentally induced mitral valve insufficiency in dogs suggests that ACE inhibitor therapy may not improve the outcome for patients with pre-clinical CMVI due to its negative impact on protein metabolism and myocardial function. Beta blocker therapy, however, shows promise in this experimental model for its ability to reverse myocardial remodeling and restore contractile function of myocytes in early mitral valve disease. Further work is required to clarify this picture.
Severe chronic mitral valve insufficiency can result in episodes of severe fulminate pulmonary edema associated with chordal rupture. It is the authors' experience that if these dogs are supported through this period of respiratory difficulty they often can revert back to a compensated form of heart failure.
Atrial fibrillation appears to markedly reduce the prognosis for Dobermans with DCM and heart failure (median survival is 9 days). Atrial fibrillation carries a far less ominous impact in other breeds with DCM and in dogs with other forms of heart failure.