Congestive Heart Failure (Systolic) Topic Review

Pathophysiology | Etiology | Symptoms | Diagnosis | Treatment | Special Situations


Congestive heart failure occurs when the cardiac output is not adequate enough to meet the demands of the body. This can occur for several reasons as congestive HF is the predominant clinical presentation in multiple disease states.

Congestive HF can be due to the following:

  • Systolic dysfunction (reduced ejection fraction)
  • Diastolic dysfunction (relaxation or filling abnormality)
  • Valvular heart disease
  • Right heart failure
  • Arrhythmia
  • High output CHF (i.e. severe anemia, arteriovenous malformations)

A review of systolic congestive heart failure is presented here. Reviews of diastolic congestive heart failure, valvular heart disease, right heart failure and high output heart failure are presented elsewhere.

Congestive heart failure affects approximately 6 million Americans every year and remains one of the most common reasons for hospitalization.

The American College of Cardiology/American Heart Association classification of heart failure has four stages.

Stage A: Patients at risk for heart failure, but who have not yet developed structural heart changes (i.e. those with diabetes, those with coronary disease without prior infarct)
Stage B: Patients with structural heart disease (i.e. reduced ejection fraction, left ventricular hypertrophy, chamber enlargement) who have not yet developed symptoms of heart failure
Stage C: Patients who have developed clinical heart failure
Stage D: Patients with refractory heart failure requiring advanced intervention (i.e. biventricular pacemakers, left ventricular assist device, or transplantation)

Note that the ACC/AHA classification is much different than the New York Heart Association (NYHA) functional class (described below in Symptoms) in that there is no moving backwards to prior stages. Once symptoms develop, stage C heart failure is present and stage B will never again be achieved. In the NYHA classification, in contrast, patients can move between class I and class IV relatively quickly, as these are all designated on symptoms alone.

Pathophysiology – Congestive Heart Failure

CHF results in the activation of multiple compensatory mechanisms in an attempt to increase cardiac output. These frequently work in the short term; however, the long-term effects can be detrimental to the heart via negative remodeling. The two primary mechanisms — considered the “neurohormonal” response — are activation of the sympathetic nervous system (SNS) and activation of the renin-angiotensin-aldosterone (RAAS) system. Medical therapy is aimed at reducing the activity of these two systems. A third compensatory response occurs via B-type natriuretic peptide and A-type natriuretic peptide. See the summary image below.


When the carotid baroreceptors sense a low blood pressure, one response is to activate the sympathetic nervous system (SNS). This increases epinephrine and norepinephrine levels, which act to increase heart rate, contractility and afterload via peripheral vasoconstriction. In the short term, this will work to increase cardiac output and relieve heart failure symptoms; however, chronically this has deleterious effects and causes further left ventricular systolic decline. Beta-blockers are the primary therapy to reduce this SNS activation.

When the renal perfusion is decreased, the kidney assumes hypovolemia — although that is not always the case, as low cardiac output can also decrease renal perfusion. The inherent compensatory mechanism to retain sodium and water is activation of the renin-angiotensin-aldosterone system. Angiotensin increases afterload via peripheral vasoconstriction, raising blood pressure. The activation of the RAAS has been shown to contribute to negative remodeling of the heart, resulting in even worse overall cardiac function. The RAAS can be blocked by angiotensin converting enzyme inhibitors, angiotensin receptor blockers, aldosterone antagonists and antidiuretic hormone antagonists, as described in Treatment below.

Both B-type natriuretic peptide and A-type natriuretic peptide have beneficial hemodynamic effects during heart failure and represent another natural mechanism to relieve symptoms. They are released primarily in the atrium as the elevated cardiac pressures stretch the atrial myocytes. They act to vasodilate and cause sodium excretion, resulting in natriuresis. Nesiritide is a B-type natriuretic peptide analog that can be used to treat heart failure.

Endothelin has negative effects in regards to remodeling and vasoconstriction; however, clinical trials of endothelin inhibitors have never shown a benefit, and thus its role remains unclear.

Etiology – Congestive Heart Failure

There are numerous causes for systolic heart failure, but the most common is related to coronary artery disease and prior myocardial infarctions. This entity is termed an “ischemic cardiomyopathy” and accounts for nearly half of systolic heart failure cases in the United States.

Dilated cardiomyopathy is the second leading cause of systolic heart failure. This can be idiopathic (50% of cases), a viral cardiomyopathy, peripartum and hypertensive heart disease (related or from less common causes). These include doxorubicin therapy, stress-induced (Takotsubo), alcohol-related, selenium or thiamine deficiency, tachycardia-mediated, giant cell arteritis, hyperthyroidism, cocaine use, obstructive sleep apnea and familial cardiomyopathies.

Valvular heart disease is the third leading cause of systolic heart failure. This includes aortic valve stenosis, aortic valve regurgitation, mitral valve stenosis and mitral regurgitation. In many developing nations, the most common cause of systolic heart failure is Chagas disease, related to Trypanosoma cruzi, transmitted by triatomine bugs.

Recall that right heart failure and diastolic heart failure are different entities from the left-sided systolic heart failure reviewed here. The most common cause of right heart failure is pressure overload related to left heart failure. Diastolic heart failure is most commonly caused by hypertension as a part of “hypertensive heart disease.” Aging of the heart contributes to diastolic heart failure as well.

Symptoms – Congestive Heart Failure

The general symptoms of congestive heart failure are the same regardless of the etiology and attributed to either fluid retention, related to the activated RAAS, or low cardiac output. They can also be categorized as from left heart failure vs. right heart failure.

Left heart failure will result in low cardiac output symptoms and transmission of the increased left-sided cardiac pressures into the lungs causing pulmonary edema and a sense of dyspnea. With physical exertion, the heart demands increased cardiac output that is unable to be satisfied in states of heart failure, significantly increasing left heart pressures and causing this transient pulmonary edema.

As those increased pressures from the left heart affect the right ventricle, right heart failure can ensue. The most common cause of right heart failure is left heart failure.

Right heart failure symptoms include lower extremity dependent edema. When the legs are elevated at night, the fluid redistributes centrally, causing pulmonary edema that results in orthopnea (dyspnea while lying flat) or paroxysmal nocturnal dyspnea (PND). Hepatic congestion can occur causing right upper quadrant abdominal pain.

Symptoms related to low cardiac output include fatigue, weakness and, in extreme cases, cardiac cachexia.

The New York Heart Association functional classification system helps to categorize patients based on their symptoms of heart failure.

Class I: No symptoms of heart failure
Class II: Symptoms of heart failure with moderate exertion such as ambulating two blocks or two flights of stairs
Class III: Symptoms of heart failure with minimal exertion such as ambulating one block or one flight of stairs, but no symptoms at rest
Class IV: Symptoms of heart failure at rest

Recall that the NYHA functional classification differ from the ACC/AHA heart failure classification, in that the former allows movement from one class to the other while the latter classification does not (see below).

Diagnosis – Congestive Heart Failure

The diagnosis of congestive heart failure is predominantly by history and physical, although echocardiography and cardiac catheterization can be beneficial.

Physical examination during systolic congestive heart failure will reveal an S3 heart sound if significant left ventricular dilation is present. An S4 heart sound can be present in diastolic heart failure. The point of maximal intensity (PMI) will be laterally displaced and, at times, the S3 can even be palpable. Cardiac murmurs will be present if valvular heart disease is present contributing to the heart failure such as aortic stenosis or mitral regurgitation.

Physical examination in states of right heart failure may reveal elevated jugular venous pressure including hepatojugular reflux, lower extremity pitting edema, and ascites. Pleural effusions may be present and more prominent on the right compared to the left.

Echocardiography is indicated in all patients with a new diagnosis of congestive heart failure to help determine the etiology. The left ventricular systolic function can be measured including the ejection fraction. Diastolic function assessment can help determine the left heart pressures. The cardiac valves can be interrogated for significant regurgitant or stenotic lesions.

Cardiac catheterization including coronary angiography is indicated whenever anginal symptoms accompany a new onset of congestive heart failure (Class I). If no angina is present, stress testing to evaluated for ischemia as a contributor is recommended. Alternatively, coronary CT angiography can be done when no angina is present to exclude occlusive coronary artery disease.

Treatment – Congestive Heart Failure

Medical Therapy

Lifestyle modifications to help decrease the risk for volume overload leading to hospitalization is important. Fluid restriction to about 2 L of all liquids daily should be maintained as well as sodium restriction of 2 g daily. Monitoring daily weights at home in order to dose diuretics on an as-needed or individualized basis is recommended. Educating patients on the importance of medication compliance is crucial to prevent decompensated episodes of heart failure.

There is an abundance of clinical evidence to show many available pharmacotherapies  support mortality reduction and symptom improvement in patients with congestive heart failure. It is important to understand which therapies are the most important and reduce mortality vs. those that relieve symptoms only.

Angiotensin converting enzyme inhibitors/Angiotensin receptor blockers

Angiotensin converting enzyme inhibitors (ACE inhibitors) are a class of oral medications that act primarily through blockade of the angiotensin converting enzyme (ACE). This enzyme converts angiotensin I to angiotensin II. Angiotensin II causes vasoconstriction increasing afterload thus increasing systemic blood pressure. Angiotensin contributes to the production of aldosterone which normally acts to retain sodium and water.

Reducing the activity of the renin-angiotensin-aldosterone system is crucial in heart failure, during which it is overactive and contributes to negative remodeling. ACE inhibitors can reduce the symptoms of heart failure and have been shown in multiple clinical trials to have a mortality benefit in patients with systolic heart failure. Doses usually start low, with up-titratration to a predetermined goal dose if the patient is able to tolerate it. Commonlyused ACE inhibitors include lisinopril, captopril, ramipril and enalapril.

Angiotensin receptor blockers (ARBs) are a class of oral medications that act primarily through blockade of the angiotensin receptor. Very similar effects on the RAAS are achieved with ARBs compared with ACE inhibitors. ARBs are primarily used when a patient with systolic heart failure is unable to tolerate an ACE inhibitor, frequently due to a cough.

These drugs have been shown in multiple clinical trials to offer a significant mortality benefit.


Beta-blockers antagonize beta-1 and beta-2 receptors —  the usual targets of the sympathetic nervous system — including epinephrine and norepinephrine. The overactive SNS has deleterious effects on long-term cardiac function, as described earlier. Three beta-blockers are approved by the FDA in the United States for the treatment of systolic congestive heart failure including metoprolol succinate, carvedilol and bisoprolol.

Beta-blockers are contraindicated specifically in systolic heart failure when pulmonary edema is present and when there are signs of cardiogenic shock, severe bradycardia, hypotension or wheezing related to asthma. 

Beta-blockers should be initiated in patients hospitalized for acute systolic congestive heart failure prior to hospital discharge. It is reasonable to withhold beta-blockers in patients previously taking them in the outpatient setting for chronic systolic heart failure when they are admitted with a heart failure exacerbation.

These drugs have also been shown in multiple clinical trials to offer significant mortality benefit.

Aldosterone antagonists

Aldosterone antagonists (spironolactone, eplerenone) also known as “potassium sparing diuretics” block the action of aldosterone inhibiting the reuptake of sodium and water. Normally, when sodium reabsorbs, it is exchanged with potassium, which is then excreted. Because aldosterone inhibition decreases sodium reabsorption, it also decreases potassium excretion, resulting in higher serum potassium levels.

Spironolactone is indicated (class IIa, level of evidence B) in systolic heart failure with recent or current New York Heart Association functional class IV symptoms, preserved renal function and a normal potassium concentration.

Spironolactone was investigated in the Randomized Aldactone Evaluation Study (RALES) trial, and a mortality benefit was shown in patients categorized as New York Heart Association functional class III and IV. Significant hyperkalemia did contribute to sudden cardiac death.

The aldosterone antagonist eplerenone was evaluated in the Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) trial, leading to the recommendation for use of the agents with an ACE inhibitor prior to hospital discharge after an acute coronary syndrome if there is left ventricular systolic dysfunction (EF < 40%), either diabetes or symptomatic heart failure present and no contraindication. A class effect is likely present; therefore, spironolactone is frequently used instead of eplerenone due to cost concerns, although there is no direct data to support this practice. In this population, aldosterone antagonists to give a mortality benefit.


Digoxin blocks the sodium/potassium ATPase pump. The mechanism by which this decreases AV conduction is not clear, but is perhaps due to increased vagal tone. Intracellular calcium within the cardiac myocytes is increased by digoxin resulting in increased inotropy (contractility) and thus digoxin is frequently used when atrial fibrillation and left ventricular systolic dysfunction coexist.

Digoxin therapy gets a class I indication for the treatment of symptomatic systolic congestive heart failure. Although the Digitalis Intervention Group (DIG) trial showed no mortality benefit,  there was improvement in symptoms and fewer hospitalizations for heart failure.

Commonly, if systolic heart failure is present in combination with atrial fibrillation and an uncontrolled ventricular rate, digoxin therapy is utilized. Digoxin toxicity is a concern, and the dose must be adjusted in the setting of renal failure.


The loop diuretics furosemide, bumetanide and torsemide are utilized to help maintain euvolemia in patients with heart failure. These drugs are for symptom relief only and have never been shown to provide mortality benefit. The dose frequently needs adjusting based on the patient's lifestyle, including fluid and salt intake.

Antidiuretic hormone (ADH) antagonists

Tolvaptan is a vasopressin receptor antagonist. Vasopressin — an antidiuretic hormone, or ADH — helps to regulate water retention by absorbing water in the collecting ducts of the nephron. Blocking this receptor allows water to be excreted more readily. Many patients with heart failure present with some degree of hyponatremia from water retention. Tolvaptan has been shown in more than one clinical trial to increase sodium levels; however, mortality and rehospitalization rates were not improved, and thus the role for this therapy is not well defined. Specifically, tolvaptan is approved by the FDA for the treatment of euvolemic hyponatremia and hypervolemic hyponatremia.


Nesiritide is a recombinant form of B-type natriuretic peptide and is used for the treatment of acute decompensated heart failure. Nesiritide has potent vasodilatory properties and reduces pulmonary capillary wedge pressure effectively. This results in improvement of dyspnea.

The large Acute Study of Clinical Effectiveness of Nesiritide and Decompensated Heart Failure (ASCEND-HF) trial randomized 7,141 patients to nesiritide vs. placebo. Although nesiritide did improve the symptom of dyspnea compared with placebo, there was no reduction in 30-day rehospitalization and no mortality benefit. Hypotension was significant in the nesiritide group.

Nesiritide is not recommended for routine use during decompensated heart failure. If patients with blood pressures in the normal range are not responding well to typical management with loop diuretics, nesiritide can be considered.

Hydralazine and nitrates

Hydralazine is a direct arterial vasodilator that decreases afterload. Isosorbide mononitrate is a long-acting oral nitrate that decreases preload. The combination of these two drugs has an effect similar to as an ACE inhibitor or angiotensin receptor blocker, without reducing renal function or causing hyperkalemia. The combination of hydralazine and nitrates, however, does not have the neurohormonal blockade benefit of ACE inhibitors or angiotensin receptor blockers, which is thought to play an important role. Despite this, a clear mortality benefit has been present with this combination when ACE inhibitors or ARBs are contraindicated, especially in the African American population.

Mechanical Therapy

The treatment of heart failure with therapies other than medications, such as the use of devices, is considered mechanical therapy. This includes biventricular pacing, implantable cardioverter defibrillators (ICDs) and left ventricular assist devices (LVADs).

Biventricular pacing

Biventricular pacing is an excellent option for certain patients with advanced heart failure. Also known as “cardiac resynchronization therapy,” biventricular pacing has been shown to improve heart failure symptoms in a majority of cases. The normal cardiac conduction system delivers the electrical impulse to both the right and left ventricles simultaneously; however, in the presence of a left bundle branch block (LBBB) or right bundle branch block (RBBB), the electrical impulse will reach one ventricle first, then slowly transmit to the other, causing “cardiac dyssynchrony.” Remember that a LBBB and RBBB, by definition, prolong the QRS duration.

The indications for biventricular pacing include:

  • Left ventricular ejection fraction less than 35%, a QRS duration of greater than 120 milliseconds and NYHA functional class III or IV with optimal medical therapy
  • Left ventricular ejection fraction less than 35% and frequent reliance on right ventricular pacing (which significantly prolongs the QRS duration)
  • Left ventricular ejection fraction less than 35%, NYHA functional class I or II and undergoing pacemaker or implanted cardioverter defibrillator (ICD) insertion, potential reliance on frequent cardiac pacing

A meta-analysis has shown a mortality benefit for those patients with a QRS duration of greater than 150 ms who receive biventricular pacing, but not those with a QRS duration less than 150 ms.

Many patients who are candidates for biventricular pacing also receive an implanted cardioverter defibrillator (ICD) at the same time.

When atrial fibrillation is present, the QRS complex occurs at random intervals and the biventricular pacing device does not know when to initiate atrial pacing and may not be able to initiate biventricular pacing (if the native QRS complex comes earlier than expected). This results in less beneficial effects on cardiac output and thus symptoms.

Therefore, it is recommended that any patient with permanent atrial fibrillation undergoing biventricular pacing also have AV nodal ablation performed, thereby eliminating the unpredictability of the onset of the QRS complex and allowing for near 100% biventricular pacing.

Implanted cardioverter defibrillator (ICD)

An implantable cardioverter defibrillator (ICD) is a permanent device in which a lead (wire) inserts into the right ventricle and monitors the heart rhythm. It is implanted similarly to a pacemaker and the generator lays in the upper chest area. Therapies are delivered in the form of anti-tachycardia pacing (ATP) or shocks to convert to sinus rhythm from sustained ventricular tachycardia or ventricular fibrillation — both of which are life-threatening rhythms.

For primary prevention of sudden cardiac death, ICDs are indicated in the following situations:

  • Patients with a prior myocardial infarction (at least 40 days prior to allow time for recovery of LV systolic function) and a left ventricular ejection fraction of less than 30%
  • Patients with systolic heart failure (New York Heart Association functional class II or III) and an ejection fraction less than 35%. Optimal medical therapy must be present and at least 3 months must have elapsed (in case systolic function recovers to an ejection fraction > 35%) in both non-ischemic cardiomyopathy patients and ischemic cardiomyopathy patients who underwent bypass surgery.

For secondary prevention of sudden cardiac death, ICDs are indicated in the following situation:

  • Patients with documented cardiac arrest from sustained ventricular tachycardia or ventricular fibrillation or documented hemodynamically stable sustained ventricular tachycardia even if the left ventricular ejection fraction is greater than 35%, as long as no reversible cause is identified. The above must not be within 48 hours of an acute coronary syndrome.

Left ventricular assist device

A left ventricular assist device is a surgically implanted cardiac assist mechanism that essentially acts like a heart. One cannula sits in the left ventricle which pulls blood out of the body into its chamber, where it pumps blood to the second cannula inserted into the aorta.

LVAD may be used in the settings listed below.

  • Post-operative cardiogenic shock, not able to be weaned from cardiopulmonary bypass
  • Back-up in patients undergoing high risk surgical procedures
  • Massive myocardial infarction without other therapeutic options
  • Severe cardiac decompensation (regardless of cause), such as progression of a non-ischemic cardiomyopathy
  • Bridge to transplantation
  • Chronic heart failure with a poor prognosis  but not a transplant candidate (LVAD implantation in this situation is termed “destination therapy” because the patient’s final destination is not transplant; they will have the LVAD until death.)

Special Situations – Congestive Heart Failure

Heart failure exacerbations

When a patient becomes volume-overloaded and presents with an acute episode of symptomatic heart failure, the term “heart failure exacerbation” is used.

Determining the etiology of heart failure exacerbation is crucial in order to direct medical therapy appropriately — not only to improve the current heart failure symptoms, but to prevent recurrence.

Every patient with heart failure presenting to the emergency room or hospital ward should be evaluated for the following:

  • Dietary non-compliance: Consuming large amounts of fluids and/or sodium can result in volume overload causing symptoms of heart failure and eventual pulmonary edema.
  • Medication non-compliance: Frequently, diuretics are not taken as prescribed due to the urinary side-effects. Also, uncontrolled hypertension from not taking other cardiovascular medications can contribute.
  • Ischemia: Acute coronary syndromes or progression of ischemic heart disease can cause heart failure exacerbations. All patients with heart failure in the hospital should have at least one ECG performed as well as cardiac enzymes.
  • Arrhythmia: Multiple different arrhythmias can occur in patients with heart failure, resulting in volume overload from reduced cardiac output. These include atrial fibrillation and ventricular tachycardia.
  • Progression of heart failure: Worsening of the cause of the patient’s heart failure, such as progression of valvular heart disease or further LV systolic decline in ischemic or non-ischemic cardiomyopathies, can trigger heart failure exacerbations.
  • Non-cardiac illness: Pneumonia, severe sepsis, and gastrointestinal bleeding are examples of conditions that require a higher cardiac output. In patients with already reduced heart function, these can trigger clinical heart failure.

Heart transplantation

Heart transplantation is considered a last resort therapy for end-stage heart failure when the above-mentioned therapies fail. Refractory heart failure patients should be referred to a heart failure program capable of heart transplantation, especially if cardiopulmonary stress testing shows the maximal oxygen consumption, or VO2 max, is less than 10 mL/kg.

Heart transplantation can improve survival in carefully selected individuals. The surgical process itself has an approximate 5% mortality rate. Afterwards, immunosuppressant drugs including prednisone, cyclosporine and tacrolimus must be utilized in order to prevent rejection.

Heart transplantation is contraindicated in patients with severe fixed pulmonary hypertension, malignancy, any significant illness with limited survival and any illness that would be highly likely to occur in the transplanted heart. Being aged older than 70 years is considered only a relative contraindication.

Survival with heart transplantation is steadily improving. Most patients now live at least 10 years after transplantation, with the highest mortality rate within the first 6 months of transplantation.

A ranking system is used to determine eligibility for transplantation.

Status 1A: The most critically ill patients. These patients must be hospitalized and requiring mechanical or pharmacological support to sustain life (i.e. intra-aortic balloon counterpulsation, left ventricular assist device, high doses of intravenous inotropic therapy); they are New York Heart Association functional class IV.
Status 1B: Less critically ill patients, but still seriously impaired. These patients may have outpatient daily inotrope infusion; they are New York Heart Association functional class III or IV.
Status 2: The least urgent patients. These patients rarely receive transplantation because organs are in short supply and offered to status 1A or status 1B patients first; they are New York Heart Association functional class II or III.

1. ACC/AHA Guidelines and Quality Standards
2. Heart Failure Society of America - Practice Guidelines
3. Jessup M and Brozena S. Heart Failure. N Engl J Med. 2003;doi:10.1056/NEJMra021498.