Chairman: Dr DE Johnstone, Professor of Medicine and Head of the Division of Cardiology, Dalhousie University, Halifax, Nova Scotia

Primary panelists: Dr Alnoor Abdulla, Sudbury Memorial Hospital, Sudbury, Ontario; 
Dr J Malcolm O Arnold, University of Western Ontario and Victoria Hospital, London, Ontario; Dr Victoria Bernstein, University of British Columbia and University Hospital-UBC Site, Vancouver, British Columbia; Dr Martial Bourassa, University of Montreal and Montreal Heart Institute, Montreal, Quebec; Dr James Brophy, Centre Hospital de Verdun, Verdun, Quebec; Dr Ross Davies, University of Ottawa Heart Institute and Ottawa Civic Hospital, Ottawa, Ontario; Dr Martin Gardner, Dalhousie University and Victoria General Hospital, Halifax, Nova Scotia; Dr Robert Hoeschen, University of Manitoba and St Boniface General Hospital, Winnipeg, Manitoba; Dr Lynda Mickleborough, University of Toronto and Toronto General Hospital, Toronto, Ontario; 
Dr Gordon Moe, University of Toronto and St Michael's Hospital, Toronto; Dr Terrence Montague, University of Alberta, Edmonton, Alberta; Dr Marc Paquet, McGill University and Montreal Children's Hospital, Montreal; Dr Jean-Lucien Rouleau, Institut de Cardiologie de Montréal, Montreal; Dr Salim Yusuf, McMaster University and Hamilton General Hospital, Hamilton, Ontario

Secondary panelists: Dr David Bewick, Saint John, New Brunswick; Dr F James Brennan, Kingston, Ontario; Dr Claude Chartrand, Montreal; Dr Denis Coulombe, 
Ste-Foy, Quebec; Dr Bibiana Cujec, Saskatoon, Saskatchewan; Dr Paul Daly, Toronto; 
Dr David Fitchett, Montreal; Dr Victor Huckell, Vancouver; Dr Dante Manyari, Calgary, Alberta; Dr F Neil McKenzie, London, Ontario; Dr Andrew Morris, Winnipeg; Dr George Sandor, Vancouver; Dr François Sestier, Outremont, Quebec; Dr Bruce Sussex,
St John's, Newfoundland

Correspondence and reprints: Canadian Cardiovascular Society, 360 Victoria Avenue, Room 401, Westmount, Quebec H3Z 2N4

The Principal Goal of the Canadian Cardiovascular Society Consensus Conference on the Diagnosis and Management of Heart Failure was to formulate practice guidelines for physicians who manage patients with heart failure. Several principles were adhered to in the preparation of the consensus report. Available scientific literature was reviewed, with evidence supporting the specific recommendations presented prior to making consensus recommendations regarding the diagnosis and management of patients with heart failure. As in previous Consensus Conferences (1), the panel agreed to adhere to guidelines for evaluating scientific evidence, and to provide clinicians with the range of recommendations, ranging from those based on definitive clinical trials to clinical guidelines based principally on the expert opinion of the Consensus Panel. Recommendations were made concerning the diagnosis and management of heart failure patients in a variety of clinical settings and dealing with patients of varying age and severity of heart failure. It was agreed that the recommended investigative procedures should be least harmful and therapy most beneficial to the patient. In line with the Canadian Medical Association's guiding principles for the development and implementation of clinical practice guidelines, the overall thrust of the recommendations was to improve the quality of care of patients with heart failure and to ensure the efficient use of health care resources (2). 

The format of the consensus recommendations was based on a modification of Sackett's guidelines for evaluating evidence (3) as follows: diagnostic procedures or therapies that are strongly recommended in all patients with heart failure were supported by the results of one or more large, randomized clinical trials with definitive results. The remaining recommendations represent practice guidelines for the diagnosis and management of patients with heart failure, and were based on results of less definitive clinical trials or from descriptive clinical studies. In some instances, where definitive outcome data were not available, and dealing with clinical problems that are unlikely to be studied in a rigorous, scientific manner, specific recommendations were recommended based on the expert opinion of the panel. Examples of the latter include the recommendation that a thorough history and physical should be performed in all patients with heart failure, or recommendations dealing with the general relief of suffering and amelioration of symptoms in patients with heart failure. 

Recommendations in this consensus report, therefore, were based on the science, as well as the practice, of medicine, with the general understanding that neither alone could adequately address the various diagnostic and management decisions required in patients with the complex syndrome of heart failure. 

DEFINITION

In this report, heart failure (HF) is defined as a pathophysiological state in which an abnormality of cardiac function is responsible for the failure of the heart to pump blood at a rate commensurate with the requirements of the metabolizing tissues and/or to be able to do so only from an elevated filling pressure (4). 

MORTALITY AND MORBIDITY

Congestive heart failure is a syndrome characterized by an exceedingly high morbidity and mortality. Some of the earliest data regarding the natural history from the Framingham Heart Study (5) indicated that the five-year survival rate was 50%. Recent data suggest that mortality rates may be as high as 40 to 50% at two years (6). In addition to the high death rate, patients with heart failure are hospitalized frequently. In the SOLVD Registry (7), approximately 40% of patients were hospitalized at least once within a year of diagnosis. The most common cause for hospitalization for heart failure was the development of refractory heart failure, with hospitalization for angina being the second most common reason. The absolute number of deaths from congestive heart failure has steadily increased from 1970 to 1989, paralleling the increased age of the overall Canadian population (8). 

Morbidity, including hospital readmission, is known to be substantial, placing a severe strain on the Canadian health care system. Factors increasing the prevalence of heart failure, and consequently the number of hospital visits, include the higher proportion of the elderly in the population, increased survival in patients with established heart failure and the increasing proportion of postmyocardial infarction survivors with residual and progressive ventricular dysfunction. Major international clinical trials have attempted to evaluate various preventive and treatment strategies to reduce the increasing burden of heart failure. 

ETIOLOGY

Between 60 and 70% of adult patients with heart failure have severe left ventricular dysfunction secondary to ischemic heart disease. The prevalence of nonischemic dilated cardiomyopathy also appears to have increased during the past decade, and now accounts for approximately 20% of patients with heart failure. The presence of heart disease, plus advancing age, are the principal determinants of heart failure (6). The incidence of heart failure in men exceeds that in women at virtually all ages, probably because of the higher incidence of coronary artery disease in men than in women. Hypertension increases the risk of heart failure by about threefold, and the increase in risk is related to the severity of hypertension. Diabetes mellitus also increases the risk of heart failure from two- to sevenfold, with a greater impact in women than in men. 

In trying to determine the cause of heart failure in infants, the time of onset of symptoms is important, especially in the newborn period. Heart failure occurring at birth or during the first few hours of life is almost always due to conditions producing volume loading of the right heart, such as tricuspid or pulmonary regurgitation, systemic atrioventricular fistula, twin to twin transfusion, or to metabolic disorders such as birth asphyxia, hypoglycemia and/or hypocalcemia. When failure occurs during the first week of life, it is most often due to obstructive lesions to the left heart, such as aortic and/or mitral atresia (so called hypoplastic left heart syndrome), coarctation of the aorta, or to endomyocardial diseases such as endocardial fibroelastosis, myocarditis or storage diseases. Failure occurring after the first week of life is usually secondary to large left to right shunt at the level of the ventricles or of the great arteries, a tachyarrhythmia or an acquired myocardial disease (myocarditis, cardiomyopathy). 

PATHOPHYSIOLOGY OF HEART FAILURE

Heart failure is associated with changes involving the heart as well as the periphery (Figure 1). The initial insult is usually an abnormal increase in load or significant loss of functioning myocardium. Development of myocellular hypertrophy and alterations in collagen matrix (9) occur which ultimately result in geometric change (remodelling) of the left ventricle and reduced cardiac output. During this process, baroreflex responses are attenuated (10) and a variety of neurohormonal systems are activated (11). Some of the vasoconstrictor neurohormone systems, ie, the sympathetic nervous system, angiotensin II, aldosterone and endothelin, may also act directly on the heart by further increasing cellular hypertrophy, collagen synthesis and promoting increased cytosolic Ca2+. These actions create a cycle within the heart resulting in increased myocardial energy expenditure, hastening of cell injury and induction of lethal arrhythmias. These neurohormones also induce systemic arterial and venous vasoconstriction, vascular remodelling and endothelial dysfunction. These effects increase the afterload to the heart and promote salt and water retention in the kidney, leading to circulatory congestion. Altered blood flow to the skeletal muscle and diminished baroreceptor response to stress and pulmonary congestion further contribute to decreased exercise performance. On the other hand, other neurohormones, ie, the natriuretic peptides and some prostaglandins, are vasodilatory and natriuretic. Although these neurohormones may modulate the actions of the vasoconstrictor neurohormones to a certain degree, the extent of the modulation is usually not sufficient to break the aforementioned vicious cycles, especially in the advanced stage of the disease. 

SYSTOLIC/DIASTOLIC DYSFUNCTION

The majority of patients with chronic heart failure will have elements of both systolic and diastolic dysfunction (12). The hallmark of systolic dysfunction is a reduced cardiac ejection fraction due to myocardial injury or cell death. Systolic dysfunction is likely to be the predominant problem in patients with previous myocardial infarction or idiopathic dilated cardiomyopathy. Diastolic dysfunction reflects changes during the diastolic period and includes alterations in myocardial relaxation (tending to reflect changes in early diastole), and ventricular compliance (tending to reflect changes later in diastole). Since diastolic relaxation is not a passive process but requires energy, diastolic dysfunction may result from any condition where myocardial demands exceed supply. Ventricular interdependence and pericardial restraint will also influence diastolic function. 

Knowledge of the extent of systolic and diastolic dysfunction will direct further investigation and therapy. Significant systolic dysfunction is usually associated with ventricular dilation and can be assessed clinically by significant displacement of the apex beat, the presence of a third heart sound and sometimes the occurrence of a murmur of mitral regurgitation, reflecting left ventricular enlargement. Most of the recent large mortality trials in heart failure have enrolled patients with predominant systolic dysfunction. Diastolic dysfunction may be predominant in patients with a past history of hypertension and evidence of myocardial hypertrophy, with significant coronary artery disease and ongoing myocardial ischemia, with hypertrophic cardiomyopathy, with an infiltrative process or with constrictive physiology such as chronic constrictive pericarditis. Suspicion that a patient has predominant diastolic dysfunction is supported by the findings of pulmonary or systemic congestion and the absence of cardiomegaly, when the apex beat is less displaced than expected and if there is a fourth rather than a third heart sound. A noninvasive test to assess left ventricular size, contractility, myocardial hypertrophy and diastolic filling patterns is frequently useful in the initial assessment of most patients. Comparative studies are necessary to determine which test is best suited to assess diastolic function in patients presenting with heart failure. 

The relative contribution of systolic and diastolic dysfunction should be evaluated in each patient.

CLINICAL FINDINGS IN HEART FAILURE

Symptoms
 

In severe heart failure, symptoms will usually be obvious and generally include fatigue, dyspnea, peripheral edema, orthopnea, paroxysmal nocturnal dyspnea, cough, weight gain, abdominal discomfort, and cool extremities. Patients with less severe heart failure may be asymptomatic at rest and have only modest limitation in activities. The New York Heart Association (NYHA) classification is widely used to grade the degree of symptoms of adult heart failure patients and is outlined below. 

 

Class I	No symptoms
Class II	Symptoms with ordinary activity
Class III	Symptoms with less than ordinary activity
Class IV	Symptoms at rest

 

Physical findings in the patient with severe heart failure

Physical findings in severe heart failure may include low or normal blood pressure. However, on rare occasions, the blood pressure may be elevated. Tachycardia (heart rate 80 to 100 beats/min) is common. Pulsus alternans may be present. The periphery may be characteristically cool with edema of varying degrees being present. Patients may be diaphoretic and appear cyanotic. Rales, wheezing, pleural effusions and tachypnea may be present upon auscultation of the lungs. Tachycardia, gallop rhythms (S3 and S4) and murmurs of mitral regurgitation are very common. Palpation of the apex usually reveals a displaced apex laterally. Occasionally, due to low cardiac output, the apex will not be palpable. In severe cases of right sided failure, tricuspid regurgitation is present, the jugular venous pressure is elevated and hepatojugular reflux is positive. Hepatosplenomegaly, and occasionally ascites, may be observed. 

Clinical manifestation and grading of severity of heart failure in children
 

The NYHA classification is not practical nor accurate to determine the severity of congestive heart failure in infants and children. In order to circumvent this difficulty, the following classification system has been adapted for infants (13). 

 

Class I	No symptoms
Class II	Mild tachypnea and/or diaphoresis with feeds in infants; dyspnea on exercise in older children. No growth delay.
Class III	Marked tachypnea and/or diaphoresis with feeds or exertion and increased feeding time, and poor weight gain.
Class IV	Tachypnea, retractions, grunting and diaphoresis at rest, plus poor weight gain.

 

There are several important clinical features that are different in infants and children with heart failure compared with adults. Rales are unusual in infants, even in the presence of pulmonary edema. Neck vein distension and peripheral edema are also seldom seen in newborns and infants. Enlargement of the liver is an almost constant finding in right heart failure in children. Attention should be paid to the quality of the liver edge (sharp versus rounded) to differentiate a liver that is pushed down versus congested, and may help establish a diagnosis of heart failure in a child presenting with respiratory distress. In newborns, heart rates greater than 160 beats/min are considered abnormal, while tachy- pnea is defined in newborns as a respiratory rate of more than 60/min and more than 50/min in infants. 

Routine tests in patients with heart failure ñ Chest x-ray

Chest x-rays will characteristically show cardiomegaly, the presence of interstitial edema, vascular redistribution, peribronchial cuffing and pleural effusions. Calcification of the aortic or mitral valves may be present, as well as calcification in a left ventricular aneurysm. 

Routine tests in patients with heart failure - Electrocardiogram

ECG findings vary considerably. Atrial fibrillation and atrial flutter are common as are supraventricular and ventricular ectopic beats. Nonspecific ST-T wave changes occur, and it is not uncommon to find evidence of an old myocardial infarction or left ventricular hypertrophy. Prior Q wave myocardial infarction, particularly in two different regions, may suggest systolic dysfunction, while left ventricular hypertrophy may be associated with diastolic dysfunction. A complete left bundle branch block may represent an underlying cardiomyopathy or may obscure underlying Q waves from prior myocardial infarction. 
 

Complete blood count: Complete blood count is used to exclude anemia. Hemoglobin below 9 g/dL may precipitate or aggravate congestive heart failure. 
 

Electrolytes: Sodium is an excellent and inexpensive test that indicates neurohormonal activation. Sodium is also inversely proportional to plasma renin. Thus, the lower the sodium, the higher the renin and the worse the prognosis for survival (14). Potassium is also important. Maintenance of a potassium level of 4.0 to 5.0 mmol/L is recommended. The lower the potassium, the worse the prognosis, and the same holds true for magnesium (15). 
 

Urea and creatinine: Renal function is often abnormal in patients with severe heart failure. Both urea and creatinine may continue to increase with deteriorating left ventricular function and the need for higher doses of diuretic therapy. Electrolytes and uric acid are frequently altered by diuretic therapy. Severe right-sided heart failure may impair liver function. In relatively rare situations, occult thyroid disease and hemochromatosis may present as primary heart failure. 

CARDIAC DIAGNOSTIC TESTS

Both echocardiography and radionuclide ventriculography are valuable tools in the diagnosis and management of heart failure patients. The data obtained by these noninvasive techniques help differentiate systolic from diastolic dysfunction, exclude other causes of dyspnea such as pulmonary disease, are predictive of outcome and may guide the selection of therapy in individual patients. Each technique provides different kinds of information, and depending on the specific information sought, one or the other test may be performed. For example, echocardiography is preferred in patients with suspected valvular disease, while radionuclide ventriculography might be selected to obtain a calculation of left ventricular ejection fraction. Generally, it is not necessary to perform both studies in a patient where one test has been recently performed. The routine use of sequential echocardiography or radionuclide ventriculography in monitoring patients' outcome is yet to be established and, at present, does not replace the need to reassess the patient with a careful repeat history and physical examination. 

Echocardiography

Nuclear studies

Perfusion imaging is increasingly being used to assess myocardial viability (23). Increased pulmonary uptake of thallium-201 after exercise reflects ischemic left ventricular dysfunction and reduced prognosis (24). Persistent thallium perfusion defects on serial imaging after exercise, pharmacological stress or in the resting state were originally interpreted as representing infarcted myocardium (25). However, approximately 30% of persistent thallium defects show improved thallium uptake after revascularization, suggesting that these defects harbour some residual viable myocardium. A large number of apparently irreversible thallium defects on exercise-redistribution imaging showed improved uptake after thallium reinjection (26). 

Exercise electrocardiography

In most cases, response to therapy can be assessed clinically by asking the patients how far they can walk, how quickly they walk and whether they can climb one or two flights of stairs easily. In some circumstances, a 6 min walk test (the distance the patient can walk during 6 mins at his own chosen speed of walking) may be appropriate, as it may be more relevant to the activities of daily living than a maximum symptom-limited exercise treadmill test (27). The 6 min walk test has recently been shown to be a safe and simple clinical tool that strongly and independently predicts morbidity and mortality in patients with left ventricular dysfunction (28). Repeat exercise testing is not routinely required, especially since there can be a marked placebo effect, but in individual patients, it may be appropriate as positive reinforcement that their symptomatic condition has improved or to guide advice regarding activity. 

Ambulatory monitoring.

Cardiac arrhythmias are common in patients with heart failure (29). An underlying cardiac abnormality interacts with multiple potentially predisposing factors to produce arrhythmias in heart failure patients. Factors that may predispose to arrhythmia include ischemia, electrolyte imbalances (potassium, calcium, magnesium), hemodynamic factors (excessive chamber dilation and stretch), activation of neurohormonal mechanisms (renin angiotensin, sympathetic nervous system and atrial natriuretic peptide) and proarrhythmic effects of medications such as digoxin, diuretics, positive inotropic drugs and antiarrhythmic drugs. Ventricular arrhythmias have been characterized best, and asymptomatic ventricular premature beats occur in over 90% of all patients with heart failure, with 30 to 50% of patients reported to have nonsustained ventricular tachycardia (30). 

Approximately 30 to 40% of deaths in patients with heart failure are sudden. Although ventricular tachycardia and ventricular fibrillation are thought to be the most common arrhythmias in this setting, a high incidence of bradyarrhythmic deaths in patients with end-stage heart failure has been described (31). The high prevalence of bradyarrhythmic arrest has implications for the use of both implantable cardiac defibrillators and antiarrhythmic drugs in this patient population.

Electrophysiological studies

Electrophysiological studies are helpful to confirm the diagnosis of spontaneous sustained arrhythmias, and to select therapy for these patients. Sustained ventricular tachycardia is inducible in the majority of patients with ischemic heart disease and a previous episode of sustained ventricular tachycardia, but is much less so with other etiologies such as cardiomyopathies (32). Similarly, drug therapy is less predictable by electrophysiological studies in patients with nonischemic etiologies. The use of electrophysiology studies in heart failure patients with nonsustained ventricular tachycardia is unclear, but is being evaluated in the MUSTT study. 

Cardiac catheterization/hemodynamic monitoring

In critically ill patients, clinical assessment of the severity of the hemodynamic abnormalities is frequently inaccurate and hemodynamic monitoring may confirm the mechanism and the severity of the low output state.
 

Hemodynamic monitoring is usually not required for the initiation of therapy with vasoactive drugs in patients with stable chronic heart failure. However, it may be required frequently during stabilization of patients with severe refractory heart failure (33). 

Coronary angiography is not routinely required in patients with congestive heart failure. Most patients in whom left ventricular dysfunction is secondary to coronary artery disease have had a previous myocardial infarction and, therefore, the primary diagnosis of their condition is usually not in doubt. Patients who present with anginal symptoms despite medical therapy or documented evidence of myocardial ischemia should undergo a complete evaluation including coronary angiography, and an indication for myocardial revascularization should be determined. In some cases, the etiology of the cardiomyopathy may be uncertain, and this must be established by coronary angiography. 

TREATMENT OF HEART FAILURE

General

Diuretics

Diuretics have been one of the major therapeutic mainstays for management of heart failure (36). The principal mechanism of action is to reduce excessive salt and water retention with a reduction in preload, which results in a decrease in symptoms from pulmonary and systemic congestion. Major adverse effects include excessive reduction in preload with reduced cardiac output and aggravation of fatigue, electrolyte disturbances and neurohormonal activation. While their acute use can clearly `rescue' patients in acute pulmonary edema, it has been more difficult to evaluate the effect of diuretics on survival when used orally to treat chronic heart failure. Most symptomatic patients will require diuretic therapy, even in low doses, and combination diuretic therapy is helpful in refractory heart failure.

In mild heart failure, a thiazide diuretic may be sufficient. Potassium sparing diuretics should be used with great caution in patients who are already receiving an angiotensin-converting enzyme (ACE) inhibitor or have chronic renal failure because of the risk of hyperkalemia. Combinations of diuretics may be given to patients with severe heart failure.
 

Late afternoon or evening doses are best avoided to prevent nocturia and disturbance of sleep pattern.

It should be remembered that, if the patient is also on an ACE inhibitor, hypotension generally is an indication to reduce the diuretic dose and not that of the ACE inhibitor. Hyponatremia may occur as a result of excessive diuretic therapy, but more frequently reflects excessive activation of the renin angiotensin system and fluid retention in patients with very severe heart failure. In patients with hyponatremia, care is required when introducing or increasing the dose of ACE inhibitors, as transient hypotension may occur more frequently. However, the ACE inhibitor will generally correct the hyponatremia. Hyponatremia due to excessive diuretic therapy might be indicated by concurrent hypokalemic alkalosis and significant postural hypotension. Hypokalemia and hypomagnesemia can be reduced by the concurrent use of ACE inhibitors, but in more severe cases of heart failure, potassium supplementation is required. Hypokalemia should be avoided to prevent significant ventricular arrhythmias or precipitate digoxin toxicity. Disproportionate elevation of urea compared with creatinine often indicates too rapid or excessive diuresis.

Digitalis and other inotropic drugs

The use of positive inotropic agents in patients with heart failure has been the subject of great controversy. The variety of agents that have been proposed are generally classified as digitalis glycosides or nonglycosides, and the latter includes phosphodiesterase inhibitors, beta-adrenergic receptor agonists and dopaminergic-receptor agonists. In view of their hemodynamic profile, the phosphodiesterase inhibitors initially appeared to be a welcome addition to therapies for heart failure, but subsequent clinical trials with drugs such as milrinone and enoximone indicated that these agents were not only of no benefit, but had an adverse effect on survival (37,38). These drugs continue to be used intravenously to treat acute hemodynamic situations but they have no role in the long term management of heart failure.

Digoxin toxicity continues to be a clinical diagnosis encompassing the patient's symptoms, laboratory and electrocardiographic data. An elevated serum digoxin level is generally inadequate as sole evidence.
 

The recent observation that vesnarinone reduces morbidity and mortality in patients with heart failure (45) requires supporting confirmation studies before its routine use can be recommended.

Vasodilators

ACE inhibitor therapy has been shown to reduce mortality, improve quality of life (decrease hospitalization, increase exercise tolerance) and reduce the risk of myocardial infarction in patients with NYHA class II to IV congestive heart failure (46-48). Patients with the lowest ejection fractions and worst symptoms derive the most benefit. In asymptomatic patients with left ventricular dysfunction, ACE inhibitors have not been shown to reduce mortality, but have been shown to prevent deterioration to overt heart failure and to prevent myocardial infarction in patients with LVEF 35% or less (49). In the early infarct period, ACE inhibitors started three to 16 days postinfarction in patients with LVEF 40% or less, or transient heart failure have been shown to decrease mortality, prevent progression to overt heart failure and to reduce the risk of recurrent myocardial infarction (50,51). From the perspective of complications and side effects of therapy, no ACE inhibitor is clearly superior. Side effects include cough, which leads to discontinuation in 3 to 4% of patients. However, it must be understood that as many as 40% of heart failure patients complain of cough at one time or another, and it is more likely due to worsening heart failure than to ACE inhibitors. Hypotension can occur, and is worse in hypovolemic patients. Angioneurotic edema, skin rash and taste disturbances can also occur. Patients at greatest risk of worsening renal function and hyperkalemia include those with bilateral renal artery stenosis, renal dysfunction and hypertension. 
 

Hydralazine and nitrates in combination improve exercise tolerance and appear to improve survival in patients with NYHA class II to III heart failure (52). The improvement in survival appears to be less than with ACE inhibitors (53). Nitrates (oral or topical) improve exercise tolerance in patients with NYHA class II to III congestive heart failure (54). They can be used during the day or at night, but nitrate-free intervals are recommended. 
 

First-generation calcium entry blockers (nifedipine, diltiazem, verapamil) appear to cause deterioration of symptoms and may reduce survival (55,56). Newer calcium entry blockers (amlodipine, felodipine and nicardipine) may improve the exercise tolerance of patients with NYHA class II to III congestive heart failure (57,58), but have been as yet inadequately studied.
 

Beta-blockers
 

The pathophysiological pathways of mortality and morbidity risk in congestive heart failure that might be positively modified by beta-blockers include: increased neuroendocrine excitation, myocardial ischemia and ventricular arrhythmias. There has been a widespread reluctance to use beta-blockers in congestive heart failure for fear of worsening the congestive heart failure. Trial evidence to support the use of beta-blockers in congestive heart failure is inconclusive. There have been 14 reports of randomized controlled clinical trials of beta-blockers in patients with congestive heart failure. Most of these studies were small, averaging 58 patients, and of relatively short duration, averaging 25 weeks (59-72). Moreover, the beta-blocker congestive heart failure trials were largely of patients with idiopathic cardiomyopathy, as opposed to patients with ischemic congestive heart failure etiology. The results have been mixed; favourable in some studies, but no effect in others. One large randomized trial has addressed the impact of beta-blockers on mortality. In the Metoprolol in Dilated Cardiomyopathy trial (67) fewer patients treated with metoprolol died or required heart transplantation. Treated patients also had less clinical deterioration, improved symptoms and cardiac function. Metoprolol was started as a test dose of 5 mg twice daily; those tolerating this dose then received metoprolol by slowly increasing doses to 100 to 150 mg daily.
 

Antiarrhythmic drugs, pacemakers, devices

Antiarrhythmic therapy is indicated for patients with severe symptomatic rhythm disturbances. Patients with near miss sudden death, ventricular fibrillation and sustained ventricular tachycardia require effective therapy. Atrial arrhythmias, particularly atrial fibrillation, can result in significant disability. The use of antiarrhythmic drugs, however, is not only generally less effective and associated with increased risk of proarrhythmic effects in the setting of heart failure, but are also associated to a varying degree with negative inotropic effects, making control of heart failure more difficult. Drug therapy is recommended only for life threatening or significantly symptomatic arrhythmias. Type I agents (quinidine, procainamide, disopyramide, flecainide, propafenone) should be avoided (73). Type III drugs such as sotalol and amiodarone are effective and usually considered first-line agents. In one large randomized trial, amiodarone resulted in a significant reduction in mortality in patients with severe heart failure (74). In this study, approximately one-third of the patients had ventricular tachycardia on ambulatory monitoring. Amiodarone was started at 600 mg daily for 14 days and then maintained at 300 mg daily.

Until the results of further studies are known, drug therapy should be initiated in a hospital setting with appropriate ECG monitoring. Evidence of efficacy should be obtained through the use of electrophysiological testing or ambulatory and exercise ECG recordings. While implantable cardio- verters/defibrillators are effective in reducing sudden death, both operative and overall long term mortality are higher with device therapy in patients with heart failure, and their impact on survival in this population has yet to be determined in a controlled trial.

Patients with heart failure and atrial fibrillation may be better served by appropriate heart rate control than antiarrhythmic therapy aimed at restoring sinus rhythm. Pharmacologic therapy to control heart rate must be assessed at rest and during exertion, as digoxin alone is often ineffective in controlling the ventricular response to atrial fibrillation during exercise. Amiodarone may be considered if the goal is to restore sinus rhythm. Catheter ablation of the atrioventricular node with permanent pacemaker insertion may provide an effective alternative.
 

Pacemaker therapy is effective in patients with symptomatic bradyarrhythmias, and dual chamber or `physiological' pacing has demonstrated hemodynamic and symptomatic benefit in patients not in atrial fibrillation (75,76).

Anticoagulants

The goal of anticoagulant therapy in patients with heart failure is to prevent systemic embolization which is generally, but not necessarily, associated with a demonstrable ventricular thrombus and/or atrial fibrillation. The benefit of anti- coagulant therapy in the presence of atrial fibrillation associated with organic heart disease, with or without heart failure, is well documented and, accordingly, anticoagulation is strongly recommended (77). The lack of randomized, controlled studies makes it difficult to issue a definitive recommendation for anticoagulation in patients with heart failure and sinus rhythm. The demonstration of a thrombus tends to predict systemic embolization, but this is not a universal observation, and any benefit of anticoagulation may exist independently of a demonstrated thrombus (78).

Summary of results of major trials in heart failure or left ventricular dysfunction

Data from major clinical trials formed the basis of the recommendations concerning the medical management of heart failure in this consensus report. The results of the clinical trials in heart failure and left ventricular dysfunction are summarized in Table 1.
 
 

PATIENTS WITH HEART FAILURE AND ANGINA

Coronary artery disease is by far the most common etiological factor in patients with heart failure and, therefore, the most frequent correctable cause of cardiac dysfunction is myocardial ischemia. Severe ischemia may produce prolonged reversible regional or global depression of left ventricular function, conditions which have been termed ventricular stunning (83) and ventricular hibernation (84). Although the accurate identification of these reversible changes is often difficult, it is estimated that more than one-third of myocardial dyskinetic areas are improved after successful coronary revascularization (85). Angina pectoris is present in 40 to 50% of patients with coronary artery disease and overt heart failure (47). Coronary angiography usually shows obstructions that are amenable to myocardial revascularization in these patients. Therefore, in those with significant angina and reversible myocardial ischemia on noninvasive stress testing, coronary revascularization should be strongly considered. Procedural mortality ranges from 2 to 15% and is related to severity of congestive heart failure. Coronary artery bypass grafting appears to improve long term survival and anginal status, compared with medical therapy, in patients in whom angina is the predominant symptom and in whom the overall operative risk is less than 7% (86).
 

EMERGENCY MANAGEMENT OF ACUTE HEART FAILURE
 

Use of continuous positive airway pressure delivered by face mask in patients with cardiogenic pulmonary edema may reduce the need for intubation and mechanical ventilation (88).
 

REFRACTORY HEART FAILURE

Patients who remain symptomatic with signs of severe heart failure despite standard therapy for heart failure represent a serious medical condition. Patients with refractory heart failure have a very poor prognosis, with as many as 50% of these patients dying within three to six months. Clearly, the best option is cardiac transplantation. However, due to the limited capacity of this option, other strategies have been developed. General supportive measures form the cornerstone of therapy. These include sodium (2 g) and fluid restriction (1 L), a balanced diet and rest periods, particularly after meals. The use of various combinations of diuretics has proven useful in improving some patients with refractory heart failure. Combination diuretics, such as furosemide, thiazides, metolazone, triamterene or spironolactone can be very useful (89,90). However, the risks of combination diuretics are not negligible, and include hyper- or hypokalemia, hyponatremia and worsening renal failure. Some reliable patients can regulate their daily dosage of diuretics according to daily weights taken at home. Combination of various vasodilators can also be useful. Nitrates can easily be given with ACE inhibitors; however, when a third agent such as hydralazine is added to the regimen, careful monitoring of blood pressure is required and, in some patients, hemodynamic monitoring is needed to balance optimal therapy against the hypotensive effects of the agent. During periods of acute decompensation, a 48 to 72 h infusion of nitroglycerine (1 to 2 g/kg/min) has been found to be useful in some patients (91). A dobutamine infusion has also proven useful in some patients (39). However, regular use of dobutamine in patients without acute decompensation should be avoided, and during infusions, patients should be monitored closely for arrhythmias and any electrolyte imbalances. Finally, nitroprusside or amrinone infusions can also be considered.

VALVULAR HEART DISEASE

Valvular dysfunction lends itself to surgical intervention much more readily than left ventricular dysfunction. This may be especially true for congestive heart failure from acute valvular disruption, where surgical repair or replacement of the diseased native valve is the first consideration of therapy. If patients develop severe, irreversible left ventricular dysfunction from longstanding volume or pressure overload as a consequence of valvular disease, the therapeutic thrust should focus on enhancement of left ventricular performance with utilization of all proven effective medical therapy. If medical therapy is ineffective, then consideration of cardiac transplantation becomes appropriate.
 

PATIENTS WITH CONGESTIVE HEART FAILURE
REQUIRING NONCARDIAC SURGERY

Congestive heart failure is a major determinant of perioperative risk, irrespective of the nature of the underlying cardiac disorder (92). Mortality with surgery increases with worsening cardiac class (93,94). Patients with an S3 or distended jugular veins at preoperative examination have especially high risk for postoperative pulmonary edema (92,95,96). Patients with preoperative history of pulmonary edema or with evidence of congestive heart failure by preoperative physical examination and on chest x-ray have markedly increased risk of perioperative pulmonary edema. When surgery is urgent, intra-arterial and pulmonary artery pressure monitoring should be undertaken.
 

Patients developing overt heart failure in the postoperative setting do so in a bimodal distribution (97). The day of operation is most often associated with aggressive hydration and therefore represents the first opportunity for patients to develop pulmonary edema. The second most frequent time for developing heart failure is day 2 or day 3 where interstitial fluid is reabsorbed into the intravascular space.
 

TREATMENT OF HEART FAILURE IN CHILDREN

In infants and children, heart failure is less often due to pump failure, but more often to extracardiac anomalies or congenital cardiac malformations that produce an excessive demand on a normally functioning myocardium. Consequently, rapid identification of the cause of the heart failure is imperative so that specific treatment can be rapidly instituted. This is especially true in newborns in whom heart failure is often rapidly followed by the development of acidemia and/or hypoglycemia. Traditionally, the medical management of infants and children with heart failure has consisted of digoxin and diuretic agents. The usefulness of digoxin in infants with heart failure secondary to large left to right shunts has been questioned, and valid theoretical objections to the use of cardiac glycosides in patients whose symptoms are not due to myocardial failure, but to pulmonary systemic congestion secondary to anatomical defects have been raised (98,99). The evidence for ACE inhibitor efficacy in infants with heart failure secondary to a large left to right shunt is not conclusive, but they may be useful in some patients (100-103). Surgical correction should not be delayed in patients with large left to right shunts, cardiac failure and failure to thrive that cannot be controlled simply by medical therapy.
 

SURGICAL TREATMENT FOR HEART FAILURE

Coronary artery disease is a major cause of heart failure. Although the risk of revascularization is increased in patients with poor left ventricular function and severe coronary artery disease, long term surgical survival benefits appear greatest in patients with the most severe left ventricular function, coronary disease and anginal symptoms (85,104,105). The surgical treatment of patients with coronary artery disease and left ventricular segmental scar has shown some promise in patients with (106) and without associated life threatening arrhythmia (107).
 

CARDIAC TRANSPLANTATION

The most common indications for heart transplantation in adults are cardiomyopathy and coronary artery disease. Outcome has improved with the introduction of the immunosuppressant cyclosporine in the early 1980s. Irreversible renal or hepatic disease are contraindications to transplantation because of the nephrotoxic and hepatotoxic side effects of cyclosporine. Five-year survival now exceeds 70% (108). The 30-day mortality is 10% due to graft failure, acute rejection or infection. However, after two years, accelerated coronary artery disease, probably on an immune basis, becomes the leading cause of death (109). Transplant recipients should expect improved symptomatic status at the expense of lifelong antirejection medications, one to two rejection episodes and the need for a large number of cardiac biopsies per year.

Principal selection criteria for candidates suitable for heart transplantation are intractable heart failure despite optimal medical therapy, not amenable to conventional surgery, with a poor 12-month prognosis and with likelihood of rehabilitation. Due to the shortage of donor hearts, medical therapy for heart failure must be optimized (110), particularly with ACE inhibitors. Revascularization should be considered in selected patients with ischemic cardiomyopathy, particularly when there is a component of angina, technically bypassable coronary arteries, end-diastolic dimension less than 7 cm and reversible myocardial ischemia on cardiac imaging (111). Although both left ventricular dysfunction and decreased exercise tolerance predict a poor prognosis, there is not a close correlation between the two, and some patients with reduced systolic function can have preserved functional capacity and a favourable prognosis. Poor prognostic indicators are persistent class IV symptoms despite optimal medical therapy, severely depressed ejection fraction, poor exercise tolerance and symptomatic ventricular tachyarrhythmias (112-114). Contraindications to heart transplantation include recent malignancy, recent drug or alcohol abuse, untreated infection, irreversible renal disease (creatinine greater than 200 mol/L) or hepatic disease, irreversible pulmonary hypertension (pulmonary vascular resistance at least 6 Wood units), surgical technical factors, noncompliance with medical care, poor rehabilitation potential, severe peripheral or cerebrovascular disease, marked cachexia or obesity, and insulin-dependent diabetes with end organ disease. With experience, the number of absolute contraindications to heart transplantation have declined. Advanced age, by itself, is not an absolute contraindication; however, age greater than 60 years is frequently associated with other medical problems, especially vascular disease.
 

USEFUL TIPS IN THE DIAGNOSIS AND TREATMENT OF HEART FAILURE
 

The following points may prove useful in the diagnosis and treatment
of heart failure patients.
 

SUMMARY

Many of the recommendations presented in this consensus report are summarized in Figure 2. All patients with known or suspected heart failure should undergo a detailed history and physical examination. Other causes for the symptoms and/or clinical signs indicative of heart failure should be excluded. Routine biochemical tests, as well as a standard chest x-ray and ECG, should be performed on all patients with heart failure. Precipitating or aggravating causes of heart failure should be eliminated. Patients with potentially surgically correctable lesions, such as constrictive pericarditis, valvular disease or left ventricular aneurysm, should be referred for cardiological evaluation and the appropriate surgery. Patients with ischemic induced heart failure should be assessed for possible revascularization by either angioplasty or bypass surgery. Pending clinical findings and the degree of systolic or diastolic dysfunction present, determined by noninvasive tests, the panel made recommendations concerning the choice of various therapeutic agents.

These clinical guidelines have been developed for practising physicians who manage patients with heart failure. The process by which consensus recommendations were developed by the Canadian Cardiovascular Society was based on the principle that guidelines have the best chance of succeeding if they are developed by those who will be using them. Strategies that ensure physicians are aware of the current guidelines, and that their implementation leads to measurable improvement in the diagnosis and management of patients with heart failure must be developed. Consensus reports represent an ongoing process which is subject to revision when further conclusive evidence is obtained by ongoing and future clinical trials.
 

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