Donna Mancini, M.D.



Congestive heart failure (CHF) is a major medical problem that is steadily increasing with the rising age of the general population and overall reduction in cardiovascular mortality. In the United States, incidence is 500,000 patients per year, with a prevalence of 5 million Americans. Heart failure as the primary diagnosis accounts for 900,000 admissions annually and as a secondary diagnosis for 2.6 million admissions; CHF is now the most common hospital discharge diagnosis for those over age 65, and is believed to account for 1.5 percent of total health care spending. An estimated 2 percent of western adult populations are affected by heart failure.,

The prognosis after diagnosis is guarded and worsens with the extent of myocardial dysfunction. Almost 300,000 patients die each year either from heart failure or with heart failure as a contributory cause. In the Framingham study, the five year mortality following initial diagnosis was approximately 60 percent for men and 45 percent for women in the era prior to ACE inhibitors. More recent studies show a six year mortality of 80 percent in men and 65 percent in women. In patients with functional class IV heart failure, the one year mortality is approximately 60 percent. This decreases to 25 to 30 percent for class III and 10 to 15 percent for class II CHF.


Chronic heart failure consists of two components; myocardial failure and congestive failure. Myocardial failure is the initial insult and may result from chronic pressure overload as in hypertension, diffuse cell loss as in cardiomyopathy, or segmental cell loss as in ischemic heart disease. The result is a reduction in cardiac output and a decrease in left ventricular ejection fraction. Despite the biochemical and mechanical changes resulting from myocardial failure, experimental studies show that residual myocardial reserve exists that can be activated if the heart is appropriately stimulated. Myocardial failure is best quantified by decrease in left ventricular (LV) ejection fraction. Congestive heart failure reflects the neurohormonal and peripheral adaptive response to reduced cardiac output. Sympathetic and renin-angiotensin activation result in heightened peripheral vascular resistance and salt and water retention leading to congestion and edema. These peripheral changes correlate well with symptoms; congestive heart failure is best quantified by exercise performance.

The neurohormonal changes observed in heart failure include increased plasma catecholamines, antidiuretic hormone (ADH), atrial natiuretic factor (ANF) and activation of the renin-angiotensin-aldosterone system. Increased sympathetic nervous activity in heart failure produces an increase in heart rate and contractility. The increased sympathetic response helps to maintain the circulation early in the disease. With time, however, it may become exaggerated and contribute to the progression of the disease in what is frequently termed the vicious cycle of heart failure. Chronic impairment of left ventricular function results in a decrease in cardiac output. A reflex increase in systemic vascular resistance occurs, mediated by sympathetic activation and angiotensin II, further increasing afterload and decreasing cardiac output. Decreased renal perfusion activates the renin angiotensin system, thereby increasing preload by increasing salt and water retention. Sustained increase in catecholamines may produce cardiac necrosis and arrhythmias as well as decreased myocardial responsiveness by promoting down-regulation of the beta adrenergic pathway in the failing human heart - primarily due to reduced beta-1 density with beta-2 receptor density minimally affected.

Evaluation of Patients with Heart Failure

The most common causes of left ventricular systolic dysfunction in the United States are coronary artery disease (CAD), hypertension and idiopathic dilated cardiomyopathy. Once the syndrome of CHF has been diagnosed and the degree of left ventricular systolic dysfunction quantified, the evaluation focuses on the underlying disease and determining whether it is reversible. The diagnostic evaluation required when a patient presents with chronic heart failure includes studies necessary to:

For example, patients with valvular disease may benefit from appropriate valve replacement or repair and patients with CAD may require risk factor reduction, anti-ischemic therapy or revascularization. A transthoracic 2-D echocardiogram is particularly valuable to assess LV mass, size, function and to identify potential etiologies (i.e. valvular lesions or segmental wall motion abnormalities suggestive of CAD). CAD must be excluded as a potential contributing factor and patients with angina should undergo cardiac catheterization if they are candidates for interventional procedures or surgery. In patients with known CAD but no angina, noninvasive testing with thallium (with exercise and reinjection) may demonstrate ischemic or viable tissue. In patients with CHF and multiple CAD risk factors, a similar approach should be taken - i.e. noninvasive testing to exclude reversibly ischemic tissue.

TABLE 1: Recommended diagnostic studies for patients with CHF

  • Detailed history and physical exam

  • CBC, chem 20, urinalysis
  • thyroid function tests, serum iron and ferritin, urine toxicology
  • chest Xray
  • EKG
  • 2-D echocardiogram with doppler
  • Non-invasive stress testing in patients with high probability of CAD (Stress thallium with late redistribution or reinjection)
  • In patients with prior MI but no angina, noninvasive testing to detect ischemia and assess myocardial viability (Stress thallium with late redistribution or reinjection or rest-redistribution, or dobutamine-echocardiogram)
  • Cardiac catheterization in those patients with angina and/or large areas of ischemia on noninvasive testing
  • Endomyocardial biopsy in patients with clinical suspicion of myocarditis, those receiving treatment with adriamycin and those with a systemic disease and possible cardiac involvement (hemochromatosis, sarcoid, amyloid, Loeffler’s endocarditis)
  • Therapy of Congestive Heart Failure

    Non-pharmacologic therapy is aimed primarily at the reduction of sodium intake. Patients should be told not to add salt at the table or while cooking, and taught how to read the salt content on prepared food labels. As a rule, prepared foods and fast foods have high salt content, as do some over-the-counter medications. Smoking cessation should be strongly recommended (see chapter 3), alcohol intake limited and moderate exercise suggested. Pharmacologic therapy includes treatment with ACE inhibitors, diuretics, digoxin and beta blockade. The sequence in which these agents should be added continues to evolve. ACE inhibitors are now first-line therapy for heart failure, followed by treatment with diuretics, beta blockers and digoxin. There are provocative data on therapy with spironolactone. For appropriate patients with refractory heart failure, cardiac transplantation or placement of a left ventricular assist device are last options.

    When formulating pharmacologic therapeutic strategies for the failing myocardium, one may draw an analogy to a wagon drawn by an old and tired horse. The driver could whip the horse, but this may exhaust the horse’s energy reserve and hasten its demise (inotropes). Slowing the horse’s pace conserves its energy stores so it arrives at its destination in better shape (ß-blockers). Alternatively, the driver could lighten the load by removing a portion of the cargo, reducing energy expenditure and prolonging the horse’s life (vasodilators). Purchasing a new horse would be analogous to heart transplant. At the present time we have no therapy that can clearly reverse heart failure.

    Frequently, our approach to treatment is dictated by the point at which it is being implemented. In the early stages of heart failure, the aim of therapy should be myocardial preservation rather than stimulation. Therefore angiotensin-converting enzyme (ACE) inhibition and beta blockade may be the most appropriate agents to delay the onset of congestive failure and prolong survival. With advanced heart failure, symptomatic relief and prolongation of survival are the major goals.

    TABLE 2: New York Heart Association Classification of Heart Failure

    Class 1: Minimal

    • No limitation: Ordinary physical activity does not cause undue fatigue, dyspnea or palpitations.

    Class II: Mild

    • Slight limitation of physical activity: Such patients are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea or angina.

    Class III: Moderate

    • Marked limitation of physical activity: Although patients are comfortable at rest, less than ordinary activity will lead to symptoms.

    Class IV: Severe

    • Inability to carry on any physical activity without discomfort: Symptoms of congestive failure are present at rest. Any physical activity increases discomfort. Patient has PND.

    Adapted from source .

    Recently the American College of Cardiology and the American Heart Association released new guidelines for the management of heart failure and introduced a new staging system analogous to that used in other disease states such as cancer (ACC/AHA Guidelines 2001). It is meant to complement the functional assessment provided by the New York Heart Association Classification and is as follows:

    TABLE 3: Stages of Heart Failure





    Patients at high risk for the development of heart failure due to conditions associated with the development of CHF

    No structural Heart disease. No signs or symptoms

    Hypertension, diabetes, coronary heart disease, alcohol abuse, prior cardiotoxic drug


    Patients who have developed structural heart disease that is strongly associated with the development of heart failure but who have no signs or symptoms

    Structural heart disease without symptoms

    LVH, prior MI, left ventricular enlargement


    Patients with current or prior symptoms of heart failure associated with underlying structural heart disease

    Structural heart disease with symptoms

    Dyspnea or fatigue; asymptomatic patients undergoing treatment for prior symptoms of heart failure


    Patients with advanced structural heart disease and marked symptoms of heart failure at rest despite maximal medical therapy and who require specialized interventions

    End stage non-reversible disease

    Patients requiring multiple hospitalizations for CHF, patients on intravenous inotropes or left ventricular assist devices.


    Studies such as SOLVD indicate that vasodilators are beneficial early in heart failure. In class I patients, reduction in afterload and decreased myocardial tension by lowered intraventricular pressure and dimension may decrease the amount and progression of reactive hypertrophy. Thus, therapy with vasodilators is thought to delay the overall deterioration of cardiac function. Animal studies by Pfeffer et al. support this concept. While patients with class I CHF are asymptomatic, they frequently receive no drug therapy. However, treatment with ACE inhibitors may prevent the development of congestive symptoms (as well as reducing mortality after acute myocardial infarction). In the SOLVD prevention trial, treatment with enalapril decreased the incidence of clinical CHF and reduced the rate of hospital admissions when compared to placebo. In the SAVE trial, patients with acute MI and EF less than 40 percent treated within two weeks with captopril derived a 19 percent reduction in the risk of death compared to those treated with placebo. Only vasodilators have been demonstrated to prolong survival in placebo-controlled trials of patients with heart failure. The question of whether we should screen with echocardiography for asymptomatic left ventricular dysfunction remains a contentious one; we do not currently recommend this strategy.

    The CONSENSUS, SOLVD, and VHEFT-II trials all support the use of ACE inhibition in patients with class II to IV heart failure unless the agents are contraindicated due to shock, angioneurotic edema or significant hyperkalemia. Low doses are initially used (captopril 6.25 mg tid, enalapril 2.5 mg bid, lisinopril 5 mg qd) and slowly titrated up over weeks to targeted doses (captopril 50 mg tid, enalapril 20 mg bid, lisinopril 40 mg qd). The ATLAS trial demonstrated that intermediate and high doses of ACE inhibitors are more effective than very low doses., However the clinical benefit derived from high dose therapy was modest with only significant reductions in hospitalizations for CHF. The survival benefit for high and low doses ACE inhibition was comparable. Therefore use of low dose ACE inhibition is indicated in patients who are borderline hypotension. Recent trials demonstrate efficacy and safety of ACE inhibition in very old patients with heart failure (those 85 and older). Although the data to support the use of ACE inhibition in heart failure are very strong, these drugs are underused and underdosed in clinical practice.,

    Data from both VHEFT-I and VHEFT-II support the role of isordil and hydralazine for patients with class II to IV CHF, particularly when the patients are ACE intolerant. In VHEFT-I, combined therapy with hydralazine plus isosorbide dinitrate produced a modest increase in survival as compared to placebo or prazosin in patients with moderate heart failure receiving optimal doses of digoxin and diuretics. This survival was identical to the subsequent hydralazine-isordil limb of VHEFT-II. Some studies have suggested benefits from combined ACE-hydralazine-isordil therapy. The combination of ACE-inhibition and angiotensin II receptor blockade has also been investigated and preliminary trials suggest that angiotensin II type 1 receptor blockers (ARBs) provide additional benefit in patients with severe heart failure., The recent Valsartan in Heart Failure trial (VAL-HeFT-abst only) investigated the benefit of adding AII blockade to other therapy for heart failure including ACE inhibition and beta blockade. In a preliminary report, valsartan reduced the combined endpoint of mortality and morbidity from CHF but not mortality alone. Subgroup analysis suggested that the addition of AII therapy to combined ACE inbition and beta blockade may actually be deleterious. However, this needs to be confirmed in larger trials.

    Comparative trials of ACE inhibitors to AII antagonists have been performed. In the initial ELITE I trial that compared losartan to catopril, it was suggested that the effect on mortality may be greater with AII antagonists (ELITE I). However the larger and longer ELITE II trial showed a trend for better survival in the patients receiving ACE inhibitors (ELITE II). Thus at this time AII antagonists are recommended only for use in patients who are intolerant of ACE inhibitors due to angioedema or intractable cough.


    Patients with heart failure develop sodium retention and generally require therapy with diuretics. Diuretics reduce symptoms more rapidly than any other drug used in heart failure. This class of drugs is the only group that can control the fluid retention that develops with heart failure; however, they should not provide sole treatment for heart failure. The most common error in the outpatient management of patients with heart failure is under-dosing of diuretic therapy.

    In patients with mild heart failure, thiazide diuretics are used first. When the heart failure becomes more severe and renal perfusion declines, loop diuretics become more effective. Patients may become unresponsive to diuretic therapy if they consume large quantities of salt, are taking drugs that block the effect of diuretics (NSAIDs including cyclo-oxygenase 2 inhibitors) or have significant impairment of renal function or perfusion. Furosemide is the most frequently used diuretic in patients with moderate to severe heart failure. In patients with significant edema torsemide may be preferred due to its superior absorption. When diuretic drug resistance develops, combinations of diuretic drugs that act on different segments of the nephron are often beneficial (e.g. a thiazide and a loop diuretic, or amiloride and hydrochlorothiazide) and use of intravenous agents as bolus therapy or continuous infusions.

    Hypokalemia and contraction alkalosis are frequent side effects of vigorous diuretic therapy. Acetazolamide may help to promote bicarbonate excretion in this situation, and potassium supplementation is frequently required. Spironolactone is an aldosterone antagonist with mild diuretic properties that has been shown to decrease hospitalizations and prolong survival in patients with recent or current Class IV symptoms (RALES). Its effectiveness is derived from the blocking action of aldosterone. Long term treatment with ACE inhibitors or A-II antagonists may not effectively lower aldosterone levels. Aldosterone can have deleterious effects on the structure and function of the heart. The most common adverse side effects of aldactone are hyperkalemia and gynecomastia. Patients should have a serum potassium of less than 5.0 mmol/L and a serum creatinine less than 2.5 mg/dl prior to initiating therapy.

    A single daily dose of diuretic at each patient’s renal threshold is generally more effective than several smaller doses of diuretics. Patients should be instructed to follow a 2 gm sodium diet, restrict fluid intake to 1,500 to 2,000 cc per day and weigh themselves daily. While being actively diuresed, patients should lose approximately 0.5 kg a day. When they achieve euvolemic status ("dry weight"), diuretic therapy may need to be titrated down and adjusted according to weight fluctuations. The Agency for Health Care Policy and Research and the American College of Cardiology have published guidelines for the outpatient management of heart failure, both of which stress that for stable patients, carefully following symptoms is more important than repeating noninvasive tests. Patients should be instructed to call their physician if they have an unexplained weight gain of more than five pounds and regular follow-up should be scheduled. Tele-monitoring can reduce emergency department visits and hospitalization in patients with severe heart failure.

    Inotropic Agents

    Digoxin has been used in patients with congestive heart failure for over 200 years. The efficacy of digoxin therapy for patients in sinus rhythm remained controversial for many years, however several recent studies support the effectiveness of the drug in both early and advanced heart failure in all patients.,, Digoxin remains the only effective oral inotrope currently available. Its beneficial effect may result both from positive inotropy and from withdrawal of sympathetic tone.

    Beta Blockade

    Chronic beta blockade has been demonstrated to alleviate symptoms, improve hemodynamics and reduce the frequency of hospitalization in studies involving selected groups of patients with dilated cardiomyopathy., Potential mechanisms for efficacy of chronic beta blockade include both direct myocardial effects and peripheral effects. Chronic beta blockade may afford a myocardial protective effect by blocking the direct toxic effects of catecholamines. Prolonged infusion of high dose catecholamines can produce patchy diffuse myocardial necrosis in experimental animals; beta blockade may upregulate beta receptors and thus improve hemodynamic response to catecholamine stimulation. It may restore the ability of the noradrenergic sympathetic nerves to synthesize norepinephrine. Other potential actions include anti-ischemic and anti-arrhythmic effects as well as prevention of a hypertrophic response. Beta blockade will also interrupt neurohormonal stimulation characteristic of heart failure. It will directly block sympathetically induced arterial and venous vasoconstriction and will reduce renin-angiotensin and ADH stimulation.

    Beta-blockers that are effective in the treatment of heart failure include selective beta1 receptor blockers (bisoprolol and metoprolol) and non-specific beta blockers with alpha 1 antagonist properties (carvediol). Carvedilol is a non-selective beta blocker and alpha blocker as well as a potent antioxidant. In four placebo-controlled double-blind studies which enrolled a total of 1094 patients, cardiovascular mortality was significantly decreased in all classes of heart failure as was the rate of hospitalization. These results may be difficult to apply in clinical practice because of pre-randomization open-label run-in periods to select patients for the studies.. Beta-blockers other than carvedilol may also have a mortality benefit in class II-III CHF, as demonstrated in the CIBIS II and MERIT-HF trials. Long-acting metoprolol, for example, has been shown to reduce the combined endpoint of total mortality and all-cause hospitalization by almost 20 percent. A recently completed trial using carvediol in stable severe Class IIIB-IV CHF demonstrated a significant reduction in mortality (COPERNICUS)


    Antiarrhythmic Agents

    Asymptomatic ventricular arrhythmias should not be treated in heart failure. Amiodarone has no adverse effect in patients with heart failure and some studies have suggested an improvement in survival in patients with dilated cardiomyopathy. Routine use of this agent for the prevention of sudden death is not recommended at this time. Implantation of a cardioverter-defibrillator (AICD) can improve survival in patients with reduced ejection fraction, non-sustained ventricular tachycardia and inducible VT on EP testing (MADIT). However, the role of implantation of devices in patients with heart failure is preventing sudden death remains unclear and several trials designed to clarify this question are underway.

    Many patients with heart failure have widened QRS complexes that reflect asynchronous contraction of right and left ventricles. Recent trials show that biventricular pacemakers that electrically activate the right and left ventricles in a synchronized manner improve ventricular contraction and reduce secondary mitral regurgitation. Improvement in symptoms and exercise performance has been observed in short term studies but effect of this therapy on long term survival is unknown (MIRACLE-abst only).

    Cardiac Transplantation

    Selection of cardiac transplant candidates is based on accurately assessing prognosis. Generally, candidates are patients with an expected survival of less than one year. These are patients with severe (class III to IV) CHF with ejection fractions below 20 percent and documented reduced exercise capacity with measurement of oxygen consumption. Other poor prognostic indicators include: presence of coronary artery disease, intraventricular conduction defects, hyponatremia, persistent tachycardia, chronic hypotension, elevated pulmonary capillary wedge pressure and reduced cardiac index. To qualify for transplant, these patients should not have any significant co-morbidity such as severe pulmonary disease (FEV1 < 1 liter), renal insufficiency (creatinine > 2.5), cirrhosis, diabetes with end organ damage, severe peripheral vascular disease, morbid obesity, active infection, malignancy other than skin cancer, cerebral vascular disease and so on. These patients are referred to specialized transplant teams where a thorough evaluation is performed to assess both the need for transplant and eligibility.

    In patients who are non-transplant candidates, implantation of mechanical assist devices has been shown to prolong survival in a recently completed randomized prospective trial (REMATCH). Use of left ventricular assist devices as destination therapy is currently being reviewed by the FDA.

    TABLE 4: Drugs commonly used for the treatment of Chronic Heart Failure


    Initial Dose

    Maximum Dose

    Loop Diuretic



    Torseimide (demadex)

    0.5 - 1 mg daily or BID

    20 –40 mg daily or BID

    10-20 mg daily or BID

    10 mg daily

    400 mg daily

    200 mg daily




    Fosinopril (monopril)


    Quinapril (Accupil)

    Ramipril (Altace)

    6.25 mg po TID

    2.5 mg BID

    5 mg daily

    2.5 to 5 mg daily

    10 mg BID

    1.25-2.5 mg daily

    50 mg TID

    20 mg BID

    40 mg daily

    40 mg daily

    40 mg BID

    10 mg daily


    Bisoprolol (zebeta)

    Carvediol (coreg)


    Metroprolol XL

    1.25 mg daily

    3.125 mg BID

    6.25 mg BID

    12.5-25 mg daily

    10 mg daily

    25 mg po BID

    75 mg BID

    200 mg daily


    0.125 –0.25 mg daily

    0.125 –0.25 mg daily

    Additional references:

    ACC/AHA Guidelines for the evaluation and management of chronic heart failure in the adult 2001 American College of Cardiology Website

    Pitt B, Segal R, Martinez FA et al. Randomised trial of losartan versus captopril in patients over age 65 with heart failure (Evaluation of Losartan in the Elderly Study ELITE) Lancet 1997;349:747-52.

    Pitt B, Poole-Wilson P, Segal R et al. Effect of Losartan compared to Captopril on patients with symptomatic heart failure (ELITE II) Lancet 2000;3551582-1587.


    Pitt B, Zannad F, Remme W et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure (RALES). N Engl J Med 1999;341:709-717.

    Effect of Metoprolol CR/XL in chronic heart failure(MERIT-HF). Lancet 1999;353:2001-07

    Packer M, Coats A, Fowler M et al. Effect of carvediol on survival in patients with severe heart failure.(COPERNICUS) N Engl J Med 2001; 344:1651-8.


    Moss A, Hall W, Cannom D et al. Improved survival with an implanted defibrillator in patients with coronary artery disease at high risk for ventricular arrhythmia.(MADIT) N Engl J Med1996;335:1933-1940.

    Rose E, Gelijns A, Moskowitz A et al. Long term use of left ventricular device for end-stage heart failure. (REMATCH) N Engl J Med 2001;345:1435-43.