'Refractory' heart failure (HF) can be defined as HF that develops in a patient previously stable on therapy, a new manifestation of HF in a previously stable patient, or HF that does not respond as expected to therapy. The treatment of refractory HF represents a dilemma for the veterinarian. Altering or adding further medications is tempting but hazardous because heart failure patients are often haemodynamically and metabolically fragile. The goals of therapy in refractory patients are the same as in 'naïve' HF patients: improving quality of life and extending life. These goals are achieved by:

 Removing precipitating factors (e.g., treating hyperthyroidism, discontinuing corticosteroids)

 Controlling congestive signs (e.g., thoracocentesis, diuretics)

 Increasing myocardial systolic and diastolic function if impaired (e.g., positive inotropic medications)

 Reducing the workload of the heart (e.g., decrease heart rate (HR), decrease blood pressure (BP))

 Correct arrhythmias as necessary

Reasons for Recurrent or Refractory Congestive Heart Failure

Refractory HF may develop as a consequence of the cardiac disease itself (progression of cardiac disease without 'new' complications or progression of underlying abnormalities not previously recognised), or develop when complications of the current cardiac disease or medication-related problems occur. Heart failure may become refractory when the patient develops new systemic abnormalities that affect the heart or interact with cardiac medications.

Clinical Approach to the Patient

Emergency stabilisation, if needed, should take place immediately (e.g., thoracocentesis, fluid therapy or diuretic therapy as indicated). Once the patient's condition is temporarily stable, the detective work of finding the cause of recurrent or refractory heart failure begins. The reported history is important, providing the original cardiac diagnosis, medication history and information about recent changes in routine, medications or weight. It is helpful to let the owner tell you the medication doses and timing, to be sure medications are being given as prescribed. Physical examination findings may reveal evidence of new systemic illness, recurrence of previous cardiac signs or new cardiac abnormalities, or development or change in arrhythmia status (e.g., loss of HR control in atrial fibrillation). Recommended baseline testing for the newly ill patient with a history of HF should search for possible causes:

 New disease or complication: haematology, chemistry, urinalysis

 Hydration vs. congestive heart failure (CHF) status: thoracic radiographs

 New or different arrhythmia: electrogram (ECG)

 Additional testing: serum digoxin, post-pill thyroxine concentration (if applicable)

 Echocardiogram: if the manifestation of HF is unexpected, or echo findings will likely result in a change of therapy

Systemic Illness is Diagnosed

If systemic illness is severe, temporary adjustments of cardiac medications may be required (e.g., brief discontinuation of diuretics in severely hypotensive dehydrated animals). Systemic illness that occurs because of cardiac medications may lead to a permanent change in medication or dose (e.g., electrolyte imbalances, azotaemia, inappetence).

New Cardiac Signs Have Developed

Does the new sign represent progression, or does it represent a complication of the previously diagnosed heart disease (e.g., ruptured chordae tendineae with myxomatous valve disease, development of arrhythmia, development of ascites due to right-sided HF secondary to chronic left-sided HF)? Does the new cardiac sign represent a distant complication or even a new, second cardiac disease (thromboembolism (systemic or pulmonary), dirofilariasis or cardiac tumours)?

Rebalancing the Decompensated Patient

Rebalancing the decompensated patient almost always involves a short-term lifestyle change (e.g., hospitalisation, change in diet to combat inappetence, temporary cage rest or decreased exercise regimen). In addition, medication routines often change, either by addition or subtraction of medications, changes in dosing and changes in administrative route. These changes may be temporary until a systemic abnormality can be rectified, or may become permanent if disease progression has occurred.

Typical Presentation: The Hypotensive Patient

A previously balanced HF patient is presented with client complaints of weakness, lethargy, generally doing poorly or a sudden deterioration of clinical condition. The history often includes comments like... 'he hasn't been eating but he has been getting all of his medications...'. The most common cause of this presentation in a chronic HF patient is hypotension due to dehydration. This may occur due to an unexpected lack of access to water (new living situation) or because some problem has prevented the animal from accessing available water (e.g., blindness, orthopaedic problems). A frequent contributing factor to dehydration is lack of appetite, which may be drug-related (e.g., toxic concentrations or idiosyncratic reaction) or drug effect-related (i.e., prerenal azotaemia due to diuretic therapy). Vomiting or diarrhoea from any cause exacerbate dehydration. Diuretic and vasodilator administration in a dehydrated animal leads to rapidly symptomatic dehydration and hypotension.

Presenting signs in these animals are signs of low cardiac output and hypotension and include consistent rather than episodic weakness, lethargy, hiding, inappetence or anorexia, hypothermia, weak pulses and clinical signs of dehydration. Animals are often remarkably thin or muscle wasted. Cats often display hypothermia with bradycardia. Diagnostic test results compatible with low cardiac output and dehydration include a small heart on radiographs or echocardiography, BP too low to measure accurately and blood test results consistent with dehydration with or without electrolyte disturbances like hyponatraemia, hypokalaemia or hypomagnesaemia.

Therapy of the dehydrated cardiac patient with low output signs begins with temporary discontinuation of diuretics and frequently, vasodilators. Cautious rehydration should follow with potassium or magnesium supplementation if indicated. Gently warmed fluids should be administered intravenously. Other therapies may include decreasing anti-arrhythmic medications for atrial fibrillation if the ventricular response rate is too slow in a collapsed or hypotensive patient (<~140 bpm in dog, <~160 bpm in cat). Temporary catecholamine administration along with rehydration can be helpful to provide a systolic boost in dogs with dilated cardiomyopathy (DCM) or a diastolic boost in cats with hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy (RCM). Close monitoring during therapy of these patients is extremely helpful:

 Use urination or bladder filling to monitor progress of hydration

 Use respiratory rate to monitor for 'overhydration': recurrence of congestive signs

 Use appetite to monitor for overall progress (when appetite returns, gradually reinstate medications as needed)

 Monitor potassium and magnesium every 24 hours if heavy supplementation, every 48 hours if less aggressive

 Discharge when eating and breathing easily (e.g., creatinine does not have to be normal)

Typical Presentation: The Fluid Retainer

The patient may have had pulmonary oedema that was controlled and is now back, or has developed recurrent ascites or pleural effusion. History may include '...he stopped coughing but now his abdomen is swelling...'. Common causes include: natural progression of disease, sudden change in disease status, change in medications or circumstances or development of a new arrhythmia.

 Recurrent pulmonary oedema in previously stable patient. This situation commonly occurs when there is progression of the cardiac disease or if a new precipitating cause is present (e.g., new arrhythmia or introduction of new medication with HF-aggravating side effects). Physical examination following by appropriate diagnostic testing (usually ECG, radiographs, and echocardiography if indicated) can confirm the presence of worsening heart failure or arrhythmia. Therapy may include discontinuing offending mediations (e.g., corticosteroids) or treating arrhythmias if present, while temporarily increasing the aggressiveness of HF therapy with intravenous use of furosemide or catecholamines. If the patient is not yet receiving pimobendan, addition of this medication is often beneficial. Chronically, addition of more or different vasodilators, addition of digoxin to modulate neurohormonal activity and maximal neurohormonal blockade with angiotensin converting enzyme inhibitors and spironolactone is indicated.

 Right-sided heart failure develops in patient with left-sided disease. The most common presentation of this syndrome in dogs is a long-term 'cougher' due to left atrial enlargement and left-sided heart failure which develops ascites, but the cough disappears. In cats, a common presentation is pleural effusion that has previously been controlled with medication and is now recurring. If apparently 'left-sided' disease leads to right-sided failure, look for evidence of pulmonary hypertension. In animals with severe left atrial enlargement, markedly elevated left atrial pressure leads to increased pulmonary arterial pressures (pulmonary hypertension (PH)) through 'backup' of pressure. In dogs, the added load of PH on the right ventricle can lead to right heart failure; when the right ventricular output decreases, left atrial pressures decrease and cough goes away (at the cost of ascites development). In some animals, preexisting chronic lung disease may contribute to development of PH. Definitive diagnosis of PH is made by echocardiography, but several physical and diagnostic findings may support the diagnosis: accentuated second heart sounds on auscultation ± tricuspid insufficiency murmur and enlargement of both pulmonary veins AND arteries on thoracic radiographs. Echocardiographic findings consistent with PH include the usual findings of the left-sided disease plus right atrial and ventricular dilation with apparent right ventricular (RV) thickening, high velocity (>3 m/sec) tricuspid insufficiency, High velocity (>2.5 m/sec) pulmonary insufficiency and a pulmonary artery wider than the aorta in right parasternal short axis view. Therapy of right-sided HF due to PH includes mechanical removal of fluid for safety and comfort of patient and optimisation of congestive heart failure management via maximal neurohormonal blockade, addition of positive inotropes (e.g., pimobendan and/or digoxin). Atrial fibrillation rate should be controlled as needed.

 The dog with ascites gets bigger and bigger and bigger... Animals with relentless fluid retention are usually animals whose disease is progressing and that have maximal neurohormonal stimulation. Typically, the patients have right-sided disease (e.g., tricuspid dysplasia in dogs) and signs of discomfort from an increasingly tense abdomen are accompanied by (sometimes subtle) signs of low output. Therapy of these patients is supportive, and includes periodic centesis as needed for comfort of patient and maximal neurohormonal blockade (angiotensin converting enzyme inhibitors, digoxin, spironolactone). Absorption of medication in animals with severe ascites may be compromised and subcutaneous furosemide may be used to bypass absorption problems.