a. Definition. Heart failure (HF) is a syndrome that is the final common pathway for several different disease processes. It occurs when the heart is unable to supply sufficient amounts of blood at normal filling pressures to match the metabolic demands of the body. HF is commonly due to myocardial abnormalities leading to systolic and/or diastolic dysfunction, although other cardiac disorders, including abnormalities of the valves, pericardium, endocardium, and arrhythmias, can cause HF.
b. Clinical manifestations include but are not limited to fatigue, lethargy, decreased exertional tolerance, dyspnea on exertion or at rest, paroxysmal nocturnal dyspnea (PND), orthopnea, weight gain, and leg swelling. Abdominal complaints due to hepatic and splanchnic congestion may occur, as may lightheadedness related to reduced cardiac output.
c. Incidence. HF is a common disorder, primarily affecting older individuals (10% of the US population older than 70 years have this diagnosis). There are approximately 650,000 new cases diagnosed each year.
d. Mortality rates. The 1- and 5-year mortality rates for all patients with HF are ~20% and ~50%, respectively.
B. Classification. There are many different classification schemes. The most useful include the following:
a. New York Heart Association (NYHA) functional classification.
i. Class I: Symptomatic only with extraordinary activity with no limitations to physical activity.
ii. Class II: Symptomatic during ordinary activity with slight limitation to physical activity.
iii. Class III: Symptomatic with less than ordinary activity without resting symptoms.
iv. Class IV: Symptomatic at rest or with minimal activity.
b. American College of Cardiology/American Heart Association (ACC/AHA) Staging System.
i. Stage A: Patients at high risk for developing HF, but with no structural heart disease or symptoms of HF. Some of the patients included in this category are those with atherosclerotic disease (including coronary artery disease), metabolic syndrome, hypertension, or treatment with cardiotoxic medications.
ii. Stage B: Patients with known structural heart disease without symptoms
iii. Stage C: Patients with structural heart disease and past or current symptoms
iv. Stage D: Patients with end-stage disease requiring specialized therapy (i.e., mechanical support devices, intravenous inotropic agents)
v. The AHA classification was established (1) to complement the NYHA functional class system, which primarily assesses the symptom severity of patients with stages C and D and (2) to target therapy.
c. Heart failure with reduced ejection fraction (HFrEF) versus heart failure with preserved ejection fraction (HFpEF). Left ventricular dysfunction can be either systolic or diastolic. This distinction is important because patient populations, comorbid conditions, and effectiveness of treatment modalities vary in these two disease subtypes. For example, most components of HF medical therapy only improve outcomes in HFrEF.
i. HFrEF means that the heart’s contractility is compromised. The most used clinical measure of contractility is the ejection fraction, with normal left ventricular ejection fraction based on echocardiography being >52% in men and >54% in women. Therefore, patients with left ventricular ejection fraction <40% who manifest symptoms or signs of HF are classified as having HFrEF. Causes of systolic dysfunction include:
1. Myocardial infarction and ischemic heart disease: most common cause of HFrEF.
2. “Burned-out” hypertensive or valvular heart disease. Hypertensive heart disease or severe aortic stenosis initially leads to diastolic dysfunction, but with time, the heart dilates and the ejection fraction drops. Severe mitral or aortic regurgitation typically cause eccentric hypertrophy and systolic dysfunction.
3. Dilated cardiomyopathies, including those unrelated to coronary artery disease, hypertension, valvular disease, or congenital heart disease.
Heart failure with a low ejection fraction = systolic dysfunction
Heart failure with a normal or high ejection fraction = diastolic dysfunction
MNEMONIC: Common Causes of Dilated Cardiomyopathy (“PIPED DIET”)
Peripartum (last trimester or early postpartum)
Drugs (e.g., cocaine, heroin, anthracyclines, trastuzumab (Herceptin), anabolic steroids)
Dietary (thiamine deficiency, l-carnitine deficiency)
Infectious (HIV, viral cardiomyopathy)
Endocrinopathies (thyroid disorders, acromegaly, pheochromocytoma)
Tachycardia-mediated cardiomyopathy/right ventricular pacing
4. Myocarditis can be associated with systemic disorders (such as systemic lupus erythematosus, sarcoidosis, large vessel vasculitides, dermatomyositis/polymyositis) or infectious conditions (e.g., viral infections including influenza, adenovirus, HIV; protozoal causes such as Chagas’ disease; and possible bacterial and fungal infections). Giant cell myocarditis is a rare disorder that presents with fulminant myocarditis and arrhythmias. It is associated with poor prognosis.
5. Inherited cardiomyopathies, including familial dilated cardiomyopathy, noncompaction cardiomyopathy, cardiomyopathies associated with muscular dystrophies (Duchenne’s, Becker’s, myotonic), storage diseases (hemochromatosis, glycogen storage disease), or mitochondrial disorders.
HFpEF is as common as HFrEF, accounting for about 50% of patients presenting with HF.
ii. HFpEF means that the heart has normal contractility, but its ability to relax to allow adequate filling during diastole is compromised. By definition, these patients have a normal or supranormal ejection fraction of 50% or more, sign or symptoms of HF, and evidence of diastolic dysfunction or elevated levels of natriuretic peptides. Causes of diastolic dysfunction include:
1. Myocardial ischemia
2. Disorders that lead to left ventricular hypertrophy, such as:
b. Aortic stenosis
c. Hypertrophic cardiomyopathy
3. Restrictive cardiomyopathies. These are endomyocardial disorders that can be primary or secondary and are characterized by restrictive filling in the setting of normal left ventricular systolic function with reduced diastolic volumes.
Common causes of restrictive cardiomyopathy include:
Systemic (Scleroderma) or Storage diseases (hemochromatosis, Fabry’s, glycogen storage diseases)
Infiltrative (sarcoidosis, amyloidosis, malignancy)
Noninfiltrative (idiopathic restrictive cardiomyopathy, pseudoxanthoma elasticum)
Endomyocardial (endomyocardial fibrosis, hypereosinophilic syndrome, radiation or drugs causing fibrous endocarditis [e.g., methysergide, ergotamine])
iii. Heart failure with midrange ejection fraction (HFmrEF) is diagnosed in patients with signs or symptoms of HF with left ventricular ejection fraction in the 40% to 49% range. Data about patients in this group are not as robust, and outcome-improving therapies developed for HFrEF have not been proven to be of similar benefit in this group.
d. Forward versus backward failure. Forward failure is primarily characterized by low cardiac output and associated symptoms of hypoperfusion, including fatigue, weakness, lightheadedness, confusion, and loss of appetite. Backward failure results in “congestive” symptoms of pulmonary edema, such as dyspnea, orthopnea, PND, cough, and peripheral edema.
e. Left- versus right-sided failure. The distinction between left-sided and right-sided failure is based primarily on symptoms and signs found during physical examination—but these findings can be insensitive and nonspecific, especially in patients with chronic HF.
i. Left-sided failure. In left-sided HF, symptoms of pulmonary congestion and edema are present. Signs of left-sided failure include a left-sided third heart sound (S3), rales, wheezes (“cardiac asthma,” a manifestation of interstitial edema), and tachypnea. Patients with chronic systolic dysfunction often have dilated pulmonary vasculature and well-developed lymphatic drainage that is able to accommodate excess fluid, and thus pulmonary rales may not always be present.
ii. Right-sided failure. Signs of right-sided failure include a right-sided S3 (i.e., one that increases with inspiration), an elevated jugular venous pressure, abnormal hepatojugular reflux, ascites, peripheral edema, and an enlarged liver.
1. Often, evidence of biventricular failure is found during physical examination because the most common cause of right-sided failure is left-sided failure.
2. Other causes of right-sided failure include:
a. Pulmonary hypertension
b. Right ventricular infarction (usually occurring in the setting of right coronary artery/inferior wall infarction)
c. Right-sided valve disease, including endocarditis
d. Arrhythmogenic right ventricular cardiomyopathy (ARVC)
f. Shunt (left-to-right shunt)
C. Approach to the Patient
a. Determine whether the patient’s symptoms are truly due to HF. The history and physical examination remain the cornerstone of diagnosis and evaluation of patients with HF. Typical symptoms include dyspnea, orthopnea, PND, fatigue, and lower extremity edema, whereas physical examination findings that are specific for HF include a third heart sound (S3), elevated jugular venous pressure (JVP) ,and hepatojugular reflux. However, the physical examination is often limited in utility in certain patient populations (e.g., older adults, obese patients, patients with chronic obstructive pulmonary disease [COPD]). Supportive findings such as electrocardiogram (EKG), chest radiograph, and biomarker levels can be helpful. B-type natriuretic peptide (BNP) and NT-proBNP may aid in separating breathlessness from HF from noncardiac causes, especially in the emergency department setting. When HF is suspected, assess the patient’s symptoms.
Causes of elevated BNP not related to HF include:
renal failure, advanced age, anemia, pulmonary embolism, pulmonary disease (including obstructive sleep apnea), central nervous system disorders (subarachnoid hemorrhage), severe burns, and sepsis.
b. On the basis of the patient’s history, physical examination findings, and chest radiographs, categorize the failure as predominantly left-sided, right-sided, or biventricular.
c. If the patient has left-sided CHF, determine whether the dysfunction is predominantly systolic or diastolic, using the ejection fraction as a basis for this determination. Ejection fraction can be assessed using two-dimensional echocardiography, multiple gated acquisition (MUGA) scans, gated single-photon emission computed tomography (SPECT), cardiac magnetic resonance imaging (CMR), or left ventriculography during cardiac catheterization. Remember, if a patient with a normal ejection fraction has cardiogenic pulmonary edema or additional evidence for elevated filling pressures or low cardiac output, then the dysfunction is diastolic.
d. Determine the underlying cause of HF (e.g., coronary artery disease, valvular disease, hypertension, cardiomyopathy) using modalities including coronary angiogram, stress testing, cardiac magnetic resonance imaging, positron emission tomography (PET), right heart catheterization, and endomyocardial biopsy if indicated.
e. If the patient’s symptoms have worsened acutely (this is usually the scenario in patients evaluated in the emergency department), you must decide what precipitated the HF exacerbation (see section D, part f).
a. Goals of treatment of HF (and most other diseases) are twofold:
i. Reduce symptoms and improve quality of life.
ii. Reduce mortality.
b. Patient education about HF, its symptoms, and salt and fluid restrictions in addition to the importance of medication compliance.
c. Risk factor modification and treating comorbid conditions including blood pressure control, control of dyslipidemia, improvement of glycemic control in diabetic patients, treatment of atrial fibrillation, and treatment of obesity and obstructive sleep apnea.
d. Chronic HFrEF. Treatment primarily involves the following modalities:
i. Angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARB). ACE inhibitors are considered first-line therapy in all patients with reduced left ventricular systolic function including symptom-free patients (stage B) and those with prior or current HF symptoms. ACE inhibitors have been shown to improve mortality and morbidity in this patient population. If ACE inhibitors are unable to be tolerated because of cough, ARBs can be used instead.
ii. β-Blockers. These agents should be used in all potential patients with HFrEF. The key is to start treatment when the patient is stable (i.e., not during an acute exacerbation) and at low doses, slowly titrating the dose upward. β-Blockers with evidence of benefit in patients with HFrEF include sustained release metoprolol succinate, bisoprolol, and carvedilol.
iii. Mineralocorticoid receptor antagonists (MRAs)/aldosterone antagonists. Both spironolactone and eplerenone are beneficial in reducing mortality and acute HF hospitalizations in all patients with left ventricular ejection fraction <35% and NYHA class II-IV symptoms. These agents are contraindicated in the setting of severe renal dysfunction or hyperkalemia.
iv. Hydralazine/isosorbide dinitrate. This combination treatment can be added to optimal medical therapy with β-blockers, ACE inhibitors, and MRAs. It is especially relevant in (1) African Americans, in whom it has been shown to reduce mortality and morbidity; and (2) patients with HFrEF and NYHA class III–IV or as an alternative vasodilator in patients with symptomatic HFrEF who are not candidates to be treated with ACE inhibitors or ARBs.
v. Digoxin. This age-old treatment for HF has been shown to reduce symptoms but does not decrease mortality. Digoxin could be considered in patients who have symptoms despite optimal medical therapy. When used for HF, digoxin levels should be maintained in 0.5–0.9 ng/mpL range.
vi. Diuretics. Loop diuretics are the most effective and commonly used diuretics for treating symptoms of fluid overload. Some patients require synergistic dosing with thiazide diuretics when loop diuretics alone are insufficient to achieve a euvolemic state. It is useful to remember the general equivalency of commonly used loop diuretics (1 mg oral [PO] bumetanide = 20 mg PO torsemide = 40 mg PO furosemide).
vii. Angiotensin receptor–neprilysin inhibitor (ARNI). The combination of valsartan and sacubitril provides an incremental reduction in mortality and morbidity (hospitalizations) compared with adequate doses of ACE inhibitors for patients with symptomatic HFrEF. Therefore, therapy with sacubitril/valsartan should be considered in patients with chronic symptomatic HFrEF despite adequate doses of ACE inhibitor therapy. Sacubitril/valsartan is contraindicated in combination with ACE inhibitors.
viii. If-channel inhibitor (ivabradine). HFrEF patients with left ventricular ejection fraction ≤35% who are in sinus rhythm with heart rate exceeding 70 beats/min and who remain symptomatic despite optimal medical therapy with maximum tolerated doses of β-blockers, ACE inhibitors, and MRAs or who cannot tolerate β-blockers could benefit from using ivabradine to reduce HF hospitalizations.
ix. Statins may have a range of non–lipid-associated mortality benefits and should be used in patients with ischemic cardiomyopathy. In patients with nonischemic cardiomyopathy and no other indication for statins, these medications have not been shown to improve outcomes.
x. Cardiac resynchronization therapy (CRT) uses biventricular pacing to correct the dyssynchrony caused by a bundle branch block, which could contribute to worsening symptoms of HF. CRT has been correlated to improve left ventricular contractile function and ejection fraction and to reverse ventricular remodeling. As a result, CRT has been associated with a reduction in all-cause mortality and hospitalizations in at least one-third of patients undergoing biventricular pacing. CRT is beneficial in a select patient population, including symptomatic patients (NYHA class II–IV) despite optimal medical therapy who are in sinus rhythm with LVEF ≤35% with left bundle branch block and QRS duration exceeding 120 msec. CRT can also be considered in symptomatic patients (NYHA class II–IV) despite optimal medical therapy who are in sinus rhythm with LVEF ≤35% with non–left bundle branch block and QRS duration exceeding 150 msec.
xi. Advanced therapies, including mechanical circulatory support (ventricular assist devices) or heart transplantation, may be considered in carefully selected patients with stage D HF despite optimal medical therapy. Palliative home inotropes can also be considered in stage D HF patients.
xii. Arrhythmias. Sudden cardiac death accounts for 30% of deaths in patients with CHF.
1. Patients with left ventricular ejection fraction ≤35% from ischemic (assessed at least 40 days after a myocardial infarction) or nonischemic cardiomyopathy and NYHA class II–III HF experience significant survival benefit from placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden death.
2. Similarly, patients with ischemic cardiomyopathy and ejection fraction ≤30% (assessed at least 40 days after myocardial infarction) and NYHA class I symptoms also benefit from an ICD.
3. ICDs are also indicated for secondary prevention in patients who had survived sudden cardiac death.
4. Another patient population with an indication for ICD includes those with ischemic cardiomyopathy and LVEF ≤40% with evidence of nonsustained ventricular tachycardia on Holter or event monitor with inducible ventricular fibrillation or ventricular tachycardia on electrophysiology study.
e. Chronic HFpEF and HFmrEF. Digoxin and vasodilators do not play a major role in the treatment of patients with predominantly diastolic dysfunction. Diuretics are usually essential to reduce volume overload and improve pulmonary and peripheral congestion. Treatment focuses on controlling blood pressure and heart rate, maintaining fluid balance, and minimizing ischemia if present. None of the therapies of HFrEF have been shown to reduce mortality rates in HFpEF. HFmrEF patients have not been well studied.
f. Acute HF is the acute or rapid worsening of HF symptoms usually requiring emergent or urgent medical care or hospitalization. When a patient is admitted with acute HF, a search for the precipitating factor should be conducted. Remembering the following mnemonic can help:
MNEMONIC: Factors that can exacerbate HF (“FAILURE”)
Arrhythmia or Anemia
Ischemia, Infarction, or Infection
Lifestyle (e.g., increased sodium intake, stress)
Upregulators (e.g., thyroid disease, pregnancy)
Rheumatic valve or worsening of other valvular diseases
i. Both systolic and diastolic dysfunction can lead to acute HF, which can be life-threatening if not treated promptly and appropriately.
ii. Several classification systems for acute HF exist; however, a helpful clinical classification system focuses on hemodynamics, including volume status (congestion) and perfusion.
1. Patients with evidence of hypoperfusion (mental status changes, cold extremities, narrow pulse pressure, oliguria) are considered “cold” as opposed to those with no evidence of the same (called “warm”).
2. Similarly, signs of congestion (orthopnea, PND, edema, jugular venous distention, hepatojugular reflux, hepatomegaly) allow patients to be classified as “wet” as opposed to “dry.”
3. Based on the category the patient falls in, medical therapy can be aimed at improving volume status (diuretics and preload active agents such as nitroglycerin) or perfusion (inotropes such as milrinone or dobutamine and vasodilators such as nitroprusside/nesiritide or oral vasodilators including ACE inhibitors or hydralazine), or both.
iii. It is equally important to assess and treat the precipitant of HF. Acute decompensation of HF often relates to one of three groups.
1. Acute or intervening events: myocardial ischemia/acute coronary syndrome, acute or progression of valve disease, hypertensive crisis, arrhythmias, pulmonary embolism, anemia, infection or use of drugs/medications (nonsteroidal antiinflammatory drugs [NSAIDs], corticosteroids, alcohol, negative inotropic agents).
2. Medication/dietary noncompliance
3. Progression of underlying cardiomyopathy
Suggested Further Readings
Ellison DH, Felker GM. Diuretic treatment in heart failure. N Engl J Med 2017;377:1964–75.Find this resource:
Kober L, Thune JJ, Nielsen JC, et al. Defibrillator implantation in patients with nonischemic systolic heart failure. N Engl J Med 2016;375:1221–30.Find this resource:
McMurray JJ. Clinical practice. Systolic heart failure. N Engl J Med 2010;362:228–38.Find this resource:
Nohria A, Lewis E, Stevenson LW. Medical management of advanced heart failure. JAMA 2002;287:628–40. (Classic Article.)Find this resource:
Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016;18:891–975.Find this resource:
Redfield MM. Heart failure with preserved ejection fraction. N Engl J Med 2016;375:1868–77.Find this resource:
Yancy CW, Jessup M, Bozkurt B, et al. 2016 ACC/AHA/HFSA focused update on new pharmacological therapy for heart failure: an update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol 2016;68:1476–88.Find this resource: