HOW I TREAT CONGESTIVE HEART FAILURE IN DOGS

Luca Ferasin
Specialist Veterinary Cardiology Consultancy Ltd
Cardiology
Four Marks, Hampshire
United Kingdom

INTRODUCTION
Heart failure (HF) is one of the most common causes of morbidity and mortality in dogs and, when it
presents acutely (acute heart failure; AHF), represents a serious risk of death, requiring hospitalisation in
intensive care. There are several definitions for HF in the current literature but, ultimately, this should be
considered as a complex clinical syndrome that can result from any structural or functional cardiac
disorder that impairs the capacity of the heart to fill with or eject blood, with a consequent inability to fulfil
the metabolic requirement of the body tissues. Clinical signs associated with acute heart failure (AHF)
depend mostly on the underlying cardiac pathology, which may affect the endocardium (i.e. valvular
diseases), myocardium (i.e. cardiomyopathies), or great vessels (i.e. systemic or pulmonary
hypertension, arterial embolisms, etc). Most dogs in AHF present clinical signs relating to an impairment
of the left side of the heart, namely left ventricle and left atrium, but right-sided failure or biventricular
failure is also a relatively common cardiac emergency. In most dogs with heart disease, abnormalities of
systolic and diastolic dysfunction coexist, so the traditional differentiation between systolic and diastolic
failure does not have a real clinical importance.

NON-PHARMACOLOGICAL MANAGEMENT
Approaches to the management of HF can be both non-pharmacological and pharmacological; each
approach complements the other.

These interventions are mainly driven by common sense and should include the following advice:
STRATEGY ADVICE
Compliance give careful advice about disease, treatment, and prognosis (handouts; website; etc)
Salt advise patients to avoid high salt content foods and not to add salt; cardiac diet
might be advisable
Fluid avoid fluid overload and restrict their fluid intake in acute heart failure
Exercise regular gentle exercise should be encouraged
Monitoring Regular examinations to assess the severity and progression of HF
Sleeping Respiratory Rate Chart
Exercise Diary
Diet ensure adequate general nutrition and, in obese patients, advise weight reduction

PHARMACOLOGICAL MANAGEMENT
Recent studies have provided sufficient evidence to support early intervention in asymptomatic patients
with cardiac disease but not in overt heart failure. Once heart failure has developed, clinical signs can be
successfully controlled by cardiac medications and provide clinical improvement, sometimes for many
months or even years. However, the disease is inevitably progressive and the dog will eventually die or
will be euthanised due to refractory heart failure.
The medical treatment of a symptomatic patient should be aimed at reducing the severity of clinical signs,
improve the quality of life and reduce the risk of sudden death.

DIURETICS
The history of diuretics goes back a long way. It is believed that palaeolithic man discovered the caffeine-
containing plants. Xanthine derivatives and osmotic diuretics were also used due to their clinically
important diuretic effects before the emergence of modern diuretics. The development and introduction of
mercurial diuretics into therapy, at the beginning of last century, was a decisive step towards new
discoveries in the field of modern diuretics. In the mid-1950s, the first modern diuretic, acetazolamide, a
powerful carbonic anhydrase inhibitor, was developed. In the late 1950s and in the 1960s, a significant
breakthrough was achieved with the discovery of chlorothiazide, furosemide and ethacrynic acid. This era
also includes the development and introduction of potassium-retaining diuretics.
There are several types of diuretics currently used in human medicine (thiazides, carbonic anhydrase
inhibitors, loop diuretics, osmotic diuretics, potassium-sparing diuretics and aldosterone antagonists, etc).
However, in small animal cardiology, loop diuretics are most commonly used drugs for treating cardiac
congestion are loop diuretics, thiazides and potassium sparing agents.

Loop diuretics
They have a powerful diuretic action, increasing the excretion of sodium and water via their action on the
ascending limb of the loop of Henle.
Furosemide: injectable furosemide represents the first line therapeutic agent in all cases of acute CHF
because of its rapid onset of action (approximately 5 minutes if administered intravenously). Patients
receiving high dose diuretics should be monitored for renal and electrolyte abnormalities. Hypokalaemia,
which may precipitate arrhythmias, should be avoided, and potassium supplementation, or concomitant
treatment with a potassium sparing agent, should generally be used unless contraindicated.
Torasemide: this is another loop diuretic that has recently became available for the treatment of CHF in
dogs and cats (although not licenced yet for use in feline cardiology). The advantage of using torasemide
over furosemide is represented by the higher diuretic potency, prolonged half-life, and higher oral
bioavailability. Furthermore, torasemide has been reported to inhibit transcardiac extraction of
aldosterone in human patients with congestive heart failure. Due to these important properties,
torasemide can be considered as a first line treatment in chronic CHF in small animals.

Thiazide diuretics (e.g. hydrochlorothiazide)

They act on the cortical diluting segment of the nephron, inhibiting the reabsorption of sodium and
chloride. They are very safe diuretics with a low potential for toxicity problems in non-azotaemic patients
and can be used where a rapid diuresis is not necessary.

Potassium sparing diuretics (e.g. amiloride and spironolactone)

Amiloride acts on the distal nephron, while spironolactone is a competitive aldosterone inhibitor.
Potassium sparing diuretics have generally been avoided in patients receiving ACE inhibitors, owing to
the potential risk of hyperkalaemia in people, although such risk is rarely observed in small animal
cardiology. However, the overall diuretic effect of potassium sparing agents seems very mild.

Practical use of diuretics in acute heart failure

Diuretics are effective in providing symptomatic relief and remain the first line treatment, particularly in the
presence of oedema. Pleural and peritoneal effusion may also respond to diuresis, although mechanical
withdrawal (thoracocentesis and abdominocentesis respectively) should be performed for a rapid and
more efficient resolution of clinical signs. The use of diuretics in the treatment of pericardial effusion is
slightly controversial, but they can be indicated in cases of pericardial effusion secondary to CHF.
Interestingly, there are no controlled clinical studies on the clinical efficacy of diuretics in dogs and cats
with CHF and, even in human medicine, there is no direct evidence that diuretics confer prognostic
benefit in patients with congestive heart failure. In general, diuretics should be introduced at a lower
possible dose that can control the signs of congestion and this dose should be adjusted according to the
clinical response. There are dangers, however, in either undertreating or overtreating patients with
diuretics, and regular review is necessary.
In principle, a successful diuretic therapy should provide a rapid and complete decongestion in acute CHF
and, once congestion has been resolved, it should be continued to prevent it from recurring.

Diuretics in acute CHF

In veterinary practice, injectable furosemide is always used in the acute onset of CHF and its dose should
be tailored to the individual patient, since excessive doses can lead to deleterious effects on renal
perfusion (azotaemia) and electrolytes depletion (hypokalaemia, hyponatraemia, hypochloraemia,
hypomagnesaemia, and hypocalcaemia) especially in an older dogs. On the other hand, underdosing
furosemide can lead to therapeutic failure, prolonged hospitalisation, and potential euthanasia because of
refractory heart failure. If possible, furosemide should be administered intravenously to provide the most
rapid onset of action and more predictable bioavailability; however intramuscular injections may represent
a reasonable alternative in some uncooperative dogs, although the therapeutic effect may be delayed.
The author tends to use an intravenous bolus of 4 mg/kg of furosemide for severely decompensated
patients and 2 mg/kg for those with mild-moderate congestion, with an initial clinical improvement
expected in approximately 30 minutes after administration. Depending on the severity of the underlying
pulmonary oedema, repeated intravenous boluses (IVB) or initiation of continuous rate infusion (CRI, 0.66
mg/kg/h over 8 hours) of furosemide may be indicated. Constant infusions have been recommended in
the past to increase the diuretic effect while reducing the risk of renal ischaemia caused by sudden
changes in vascular volume. However, a recent study did not seem to support the suggestion that adding
CRI to an IVB loading dose IVB of furosemide might improve short term outcomes in dogs and cats in
acute CHF and, although either IVB or CRI are efficient in relieving respiratory distress to a similar extent,
CRI might carry a higher risk of dehydration and azotaemia, while IVB administration might be associated
with a longer hospitalisation duration and might require higher doses. Therefore, the use of furosemide in
acute CHF should be tailormade to take into considerations the presence of co-morbidities, such as a
concomitant renal disease, available resources, total dose of furosemide, etc.
Monitoring the respiratory rate and effort every 30-60 minutes will provide guidance on repeating
administration of furosemide. Indeed, if the furosemide dose and frequency is effective, one should notice
a gradual decrease in respiratory rate and effort over the next few hours and, based on the response to
the first dose of furosemide, one may estimate the subsequent doses and frequency of furosemide
injections. An empirical approach is to consider a cumulative maximal dose of 12 mg/kg/day.

Diuretics in Chronic HF
Diuretics should always be used in the chronic management of dogs and cats with CHF using oral tablets,
although liquid furosemide currently licensed in human medicine may also be considered, especially in
cats and small dogs, when a precise dosing may be challenging due to the available tablet strengths. A
typical maintenance dose for mild to moderate CHF is 1–2 mg/kg SID/BID, both in dogs and cats.
However, the ideal therapeutic dose can be obtained by regular monitoring of the sleeping respiratory
rate (SRR, see below). Indeed, the goal is to use the lowest dose of furosemide that effectively controls
clinical signs. Doses in excess of 12 mg/kg/day are unlikely to be beneficial and warrant the addition of a
different diuretic to control refractory failure or a proper review of the clinical management of that patient.
In some dogs and cats where diuretic-resistance is caused by a reduced drug absorption, especially in
patients with signs of right-sided CHF, chronic therapy with subcutaneous injections of furosemide may
have a marked clinical benefit.
Torasemide has been officially introduced in veterinary cardiology in the last decade. This loop diuretic
offers several advantages over oral furosemide due to its higher oral bioavailability, higher potency and
prolonged half-life, which allows a single daily administration and, ultimately, a higher owner compliance.
Although torasemide is not licensed in cats for treatment of CHF, the author has successfully used this
diuretic in cats, especially in situations where a single administration a day has significantly increased the
patient’s compliance.

Monitoring the clinical response

Most dogs and cats with a successfully controlled CHF have a SRR <30 breaths/min with a relatively
small day-to-day variability in SRR in the home environment. In dogs and cats where the clinician initially
achieves SRR <30 breaths/min, ongoing SRR measurements can be used to adjust the diuretic to the
lowest effective dose, which is the dose that maintains a SRR below 30 breaths/min. This clinical
monitoring is easy, inexpensive and can reduce side effects of an excessive diuresis.

Diuretic resistance
Diuretic resistance is defined as a failure to achieve the therapeutically desired reduction in oedema
despite a full dose of diuretic. The causes of diuretic resistance include poor adherence to drug therapy or
dietary sodium restriction, pharmacokinetic issues, and compensatory increases in sodium reabsorption
in nephron sites that are not blocked by the diuretic. Intestinal mucosal oedema is considered one of the
most common causes of diuretic resistance due to the limited absorption of oral diuretics. In addition, the
patient’s kidney function may be decreased, impairing the tubular secretion of diuretics. However, other
causes of resistance should be acknowledged, including incorrect diagnosis (eg, treating cough as a
signs of CHF) and poor owner’s or pet’s compliance.

ACE INHIBITORS
ACE-I licensed for use in the dog are enalapril, benazepril, rimapril, and imidapril; they all have shown
beneficial effects on mortality and quality of life in several prospective clinical trials and are indicated in all
stages of symptomatic CHF in this species. However, in a prospective, single-blinded, randomized
multicentre study performed on 158 dogs with MMVD and CHF, addition of the ACE-I ramipril to
pimobendan and furosemide did not have any beneficial effect on survival time.
There are currently no ACE-inhibitors licensed for use in cats with CHF; furthermore, their clinical utility
has not been confirmed in a large prospective clinical trial.

SPIRONOLACTONE
Spironolactone has generally been avoided in patients receiving ACE inhibitors, owing to the potential risk
of hyperkalaemia. However, this problem is rarely encountered in small animal cardiology and early
addition of spironolactone to standard therapy should be considered in all dogs with CHF. Since ACE-i
cannot inhibit “local” aldosterone production (chymase activity in heart and blood vessels), the use of
spironolactone can provide an additional RAAS blockade and this seems to also reduce myocardial
remodelling. In humans with class IV HF, spironolactone has shown to reduce the risk of death by 30%
and the clinical benefit of adding spironolactone to ACE inhibitor therapy has also been demonstrated in
dogs, where the addition of this drug improved patient’s quality of life and reduced the risk of cardiac-
related death, euthanasia, or worsening of mitral regurgitation by 55%.
Spironolactone added to conventional cardiac therapy decreases the risk of reaching the primary
endpoint (cardiac-related death, euthanasia, or severe disease deterioration) in dogs with moderate to
severe mitral regurgitation caused by MMVD.
A recent study has also showed that combination of benazepril and spironolactone is superior to
benazepril alone, when used with furosemide for the management of mild, moderate or severe CHF
caused by MMVD in dogs.
In a small pilot study, spironolactone seems to increase survival in cats with CHF, although additional
studies may be needed to consolidate the results of this study.

INOTROPICS and INDODILATORS

Systolic dysfunction in dogs with MVD and DCM has been clearly demonstrated, which may justify the
routine use of inotropic agents.

Digoxin
Digoxin is often classified as an inotropic agent. Although this drug is still invaluable in patients with atrial
fibrillation and coexistent CHF, improving control of the ventricular rate and allowing more effective filling
of the ventricle, its inotropic effect is very mild compared to other more powerful agents. Some
cardiologists start digoxin at an early stage to reduce the sensitivity of baroreceptors which become
"hypersensitive" in HF. Digoxin seems to reset these baroreceptors to their normal sensitivity (less
tendency to excite the sympathetic N.S.).
The therapeutic window of digoxin is very narrow and digoxin toxicity is always a potential risk, especially
in cats. Therefore, plasma digoxin level should always be measured 3-5 days after initiation of treatment
with digoxin, preferably 6-8 h after the last administration.

Pimobendan (inodilators)
It is a potent inotropic and vasodilatory agent (inodilator) The inotropic effects are mediated via
sensitization of the myocardial contractile system to intracellular calcium. Calcium sensitization allows for
a positive inotropic effect without an increase in myocardial oxygen demand. Vasodilation is mediated by
PDE III and V inhibition, resulting in arterio- and veno-dilation. It is also a positive lusitrope and has a mild
inhibitory action on platelet aggregation in dogs at standard doses. It is used for the management of
congestive heart failure due to myxomatous mitral valve disease (MMVD) or dilated cardiomyopathy
(DCM) in the dog. Indicated for use with concurrent congestive heart failure therapy (e.g. furosemide,
ACE inhibitors). Pimobendan has shown to prolong time to sudden death, euthanasia for cardiac reasons,
or treatment failure in dogs with CHF caused by MVD (Quest study: median survival time 267 days,
versus 140 days for benazepril).

It has also been used in cats with heart failure associated with systolic dysfunction, although it is not
authorized and available data suggest that the pharmacokinetics in cats differ from that in dogs. However,
a recent publication of the results of a prospective randomized placebo-controlled double-blind
multicentre study in cats with hypertrophic cardiomyopathy (HCM) and CHF did not show any benefit on a
180-day outcome.

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Ferasin L Acute heart failure in dogs. Veterinary Focus; 2022; 32.3: 75-84