Congestive heart failure

Congestive heart failure (CHF) is a clinical condition in which the heart is unable to pump enough blood to meet the metabolic needs of the body because of pathological changes in the myocardium. The three main causes of CHF are coronary artery disease (CAD), diabetes mellitus, and hypertension. These conditions cause ventricular dysfunction with low cardiac output, which results in blood congestion and poor systemic perfusion. CHF is classified as either left heart failure (LHF) or right heart failure (RHF), while a combination of both is called biventricular or global CHF. LHF leads to pulmonary edema and consequent dyspnea, while RHF leads to systemic venous congestion that causes symptoms such as pitting edema, jugular venous distension, and hepatomegaly. Biventricular CHF manifests with clinical features of both RHF and LHF, as well as general symptoms such as tachycardia, fatigue, and nocturia. In rare cases, high-output CHF may occur as a result of conditions that increase cardiac output and thereby overwhelm the heart. CHF is diagnosed based on clinical presentation and requires an initial workup to assess the severity of the disease and determine the possible causes. Initial workup includes measurement of brain natriuretic peptide levels, chest x-ray, and an ECG. Management of CHF includes lifestyle modifications and treatment of associated conditions (e.g., hypertension) and comorbidities (e.g., anemia), along with pharmacologic agents that reduce the workload of the heart. Acute heart failure may occur as an exacerbation of CHF (acute decompensated heart failure) or be caused by an acute cardiac condition such as myocardial infarction (see “Acute heart failure”).

• Congestive heart failure (CHF)
  • A clinical syndrome in which the heart is unable to pump enough blood to meet the metabolic needs of the body
  • Characterized by ventricular dysfunction that results in low cardiac output
• Systolic dysfunction
  • CHF with reduced stroke volume, reduced ejection fraction (EF)
  • Characterized by increased end-diastolic volume (EDV)
• Diastolic dysfunction
  • CHF with reduced stroke volume, normal/reduced EDV and preserved EF
  • Characterized by low myocardial compliance (due to compensatory hypertrophy)
• Right heart failure (RHF)
  • CHF due to right ventricular dysfunction
  • May result in the development of cor pulmonale in the case of isolated RHF of pulmonary origin
• Left heart failure (LHF)
  • CHF due to left ventricular dysfunction
  • Long-standing LHF is the most common cause of RHF. ^[1]
• Biventricular (global) CHF
  • CHF in which both the left and right ventricle are affected
  • Results in the development of both RHF and LHF symptoms
• Chronic compensated CHF: a clinically compensated type of CHF in which the patient has signs of CHF on echocardiography but is asymptomatic or symptomatic and stable ^[2]
• Acute decompensated CHF: sudden deterioration of CHF or new onset of severe CHF due to an acute cardiac condition (e.g., myocardial infarction)

• 1–2% of the population in the US (∼ 5.7 million individuals) has CHF. ^[3]
• The incidence is higher among African Americans and Hispanics . ^[4]
• Incidence increases with age: ∼ 10% of individuals > 60 years old are affected. ^[3]
• Systolic heart disease is the most common form of CHF overall.

Epidemiological data refers to the US, unless otherwise specified.

	Etiology of CHF [3][5]
	Systolic dysfunction (reduced EF)	Diastolic dysfunction (preserved EF)
General causes	Coronary artery disease, myocardial infarction Arterial hypertension Valvular heart disease Diabetes mellitus (diabetic cardiomyopathy) [6] Renal disease Infiltrative diseases (e.g., hemochromatosis, amyloidosis)
Specific causes	Dilated cardiomyopathy (e.g., Chagas disease, chronic alcohol use, idiopathic) Cardiac arrhythmias Myocarditis	Restrictive cardiomyopathy Hypertrophic cardiomyopathy Pericardial tamponade Constrictive pericarditis
Further risk factors	Obesity Smoking COPD Use of heavy drugs (recreational and prescribed) Alcohol abuse

The three major causes of heart failure are coronary artery disease, hypertension, and diabetes mellitus. Patients typically have multiple risk factors that contribute to the development of CHF.

Cardiac output, which is stroke volume times heart rate, is determined by three factors: preload, afterload, and ventricular contractility.

Underlying mechanism of reduced cardiac output

1. Systolic ventricular dysfunction (most common) due to:
   • Reduced contractility: damage and loss of myocytes (e.g., following myocardial infarction, CAD, DCM)
   • Increased afterload: increase in mean aortic pressure, outflow obstruction (e.g., arterial hypertension, aortic stenosis)
   • Increased preload: ventricular volume overload (e.g., backflow into the left ventricle caused by aortic insufficiency)
   • Cardiac arrhythmias
   • High-output conditions (see “High-output heart failure” below)
2. Diastolic ventricular dysfunction due to:
   • Decreased ventricular compliance: increased stiffness or impaired relaxation of the ventricle (e.g., in long-standing arterial hypertension, constrictive pericarditis, pericardial tamponade) → reduced ventricular filling and increased diastolic pressure → decreased cardiac output
   • Increased afterload: increase in pulmonary artery pressure (e.g., pulmonary hypertension)
   • Increased preload: ventricular volume overload (e.g., tricuspid valve regurgitation, left-to-right shunt)

Consequences of systolic and diastolic dysfunction

• Systolic dysfunction: reduced cardiac output → poor organ perfusion → organ dysfunction (e.g., hypotension, renal dysfunction)
• Diastolic dysfunction
  • Increased left-ventricular volume and pressure → backup of blood into lungs → increased pulmonary capillary pressure → cardiogenic pulmonary edema → orthopnea
  • Reduced cardiac output → systemic venous congestion → edema and progressive congestion of internal organs
  • Nutmeg liver: the macroscopic appearance of the liver which resembles a nutmeg seed due to ischemia and fatty degeneration from hepatic venous congestion

CHF is characterized by reduced cardiac output that results in venous congestion and poor systemic perfusion.

Compensation mechanisms

The compensation mechanisms are meant to maintain the cardiac output when stroke volume is reduced.

• Increased adrenergic activity: : increase in heart rate, blood pressure, and ventricular contractility
• Increase of renin-angiotensin-aldosterone system activity (RAAS): activated following decrease in renal perfusion secondary to reduction of stroke volume and cardiac output
  • ↑ Angiotensin II secretion results in:
    • Peripheral vasoconstriction → ↑ systemic blood pressure → ↑ afterload
    • Vasoconstriction of the efferent arterioles; → ↓ net renal blood flow and ↑ intraglomerular pressure → maintained GFR
  • ↑ Aldosterone secretion → ↑ renal Na⁺ and H₂O resorption → ↑ preload
• Secretion of brain natriuretic peptide (BNP)
  • Definition: ventricular myocyte hormone released in response to increased ventricular filling and stretching
  • Mechanism of action: ↑ intracellular smooth muscle cGMP → vasodilation → hypotension and decreased pulmonary capillary wedge pressure

General features of heart failure

• Nocturia ^[7]
• Fatigue
• Tachycardia, various arrhythmias
• S₃/S₄ gallop on auscultation
• Pulsus alternans
• Cachexia ^[8]

Clinical features of left-sided heart failure

• Symptoms of pulmonary congestion
  • Dyspnea , orthopnea
  • Pulmonary edema
  • Paroxysmal nocturnal dyspnea
    • Nocturnal bouts of coughing and acute shortness of breath
    • Caused by reabsorption of peripheral edema at night → increased venous return
  • Cardiac asthma
    • Increased pressure in the bronchial arteries → airway compression and bronchospasm
    • Symptoms mimic asthma, with shortness of breath, wheezing, and coughing. ^[9]
• Physical examination findings ^[10]
  • Bilateral basilar rales may be audible on auscultation.
  • Laterally displaced apical heart beat (precordial palpation beyond the midclavicular line)
  • Coolness and palor of lower extremities

Clinical features of right-sided heart failure

• Symptoms of fluid retention and increased CVP
  • Peripheral pitting edema: as a result of fluid transudation due to increased venous pressure
  • Hepatic venous congestion symptoms
    • Abdominal pain
    • Jaundice
  • Other symptoms of organ congestion (e.g., nausea, loss of appetite in congestive gastropathy)
• Physical examination findings
  • Jugular venous distention: visible swelling of the jugular veins due to an increase in CVP and venous congestion
  • Kussmaul sign
  • Hepatosplenomegaly: may result in cardiac cirrhosis and ascites
  • Hepatojugular reflux: jugular venous congestion induced by exerting manual pressure over the patient's liver → ↑ right heart volume overload → inability of the right heart to pump additional blood → visible jugular venous distention that persists for several seconds

In clinical practice, biventricular heart failure with features of left and right heart failure is more likely than isolated failure of one ventricle.

High-output heart failure

• Definition: heart failure secondary to conditions associated with a high-output state, in which cardiac output is elevated to meet the peripheral tissue oxygen demands
• Etiology: conditions that lead to an increased cardiac demand (high-output state) ^[11]
  • Physiological causes
    • Pregnancy
    • Fever
    • Exercise
  • Other causes
    • Anemia
    • Systemic arteriovenous fistulas (e.g., Paget disease of bone)
    • Hyperthyroidism
    • Wet beriberi (vitamin B₁ deficiency)
    • Sepsis
    • Multiple myeloma
    • Glomerulonephritis
    • Polycythemia vera
    • Carcinoid heart disease ^[12]
• Clinical features
  • Symptoms of low-output CHF ^[13]
    • Dyspnea, tachypnea
    • Tachycardia
    • Low blood pressure
    • Jugular distention with an audible hum over the internal jugular vein
  • Pulsatile tinnitus
  • Bounding peripheral pulses
  • Laterally displaced apical heart beat
  • Midsystolic murmur, S₃ gallop
• Diagnostics
  • Primarily a clinical diagnosis
  • X-ray and echocardiography: cardiomegaly
• Therapy
  • Heart failure management
    • Symptom relief
    • Hemodynamic stabilization
  • Treatment of the underlying condition

NYHA functional classification ^[14]

The NYHA (New York Heart Association) functional classification system is used to assess the patient's functional capacities (i.e., limitations of physical activity and symptoms) and has prognostic value.

NYHA class	Characteristics
Class I	No limitations of physical activity No symptoms of CHF
Class II	Slight limitations of moderate or prolonged physical activity (e.g., symptoms after climbing 2 flights of stairs or heavy lifting) Comfortable at rest
Class III	Marked limitations of physical activity (e.g., symptoms during daily activities like dressing, walking across rooms) Comfortable only at rest
Class IV	Confined to bed, discomfort during any form of physical activity Symptoms at rest

American Heart Association (AHA) classification (2013) ^[14]

The AHA classification system classifies patients according to their stage of disease. It takes objective findings (patient history, diagnostic findings) as well as symptoms of CHF into account.

Stages	Objective assessment	Corresponding NYHA functional class
Stage A	High risk of developing heart failure (e.g., pre-existing arterial hypertension, coronary artery disease, diabetes mellitus) No structural cardiac changes nor symptoms	No corresponding NYHA class
Stage B	Structural damage to the heart (e.g., infarct scars, dilatation, hypertrophy) No signs or symptoms of heart failure	NYHA I
Stage C	Structural damage to the heart Signs or symptoms of heart failure	NYHA I, II, III, IV
Stage D	Heart failure at its terminal stage	NYHA IV

Diagnostic approach ^[15]

1. Medical history, including preexisting conditions and history of alcohol and recreational/prescribed drug use
2. Initial evaluation involves a range of routine laboratory tests and a test for BNP level, ECG, and chest x-ray.
3. Echocardiography is the gold standard for the diagnosis of CHF.
4. Other procedures (e.g., exercise testing, angiography) may be required for further investigation.

Initial evaluation ^[15]

Laboratory analysis

• Elevated BNP and NT-pro BNP
  • NT-pro BNP is a precursor of BNP that is used as a diagnostic marker of heart failure.
  • High levels of BNP in patients with classic symptoms of CHF confirm the diagnosis (high predictive index). ^[16]

BNP and NT-pro BNP levels in CHF
Markers	CHF unlikely	CHF likely
BNP (ng/L) [17]	< 100	> 400
NT-pro BNP (ng/L) [10]	< 300	> 450

• Elevated atrial natriuretic peptide (ANP): Elevated levels of mid-regional pro-atrial natriuretic peptide (MR-proANP) have a good diagnostic value in suspected CHF. ^[18][19]
• Complete blood count: may show anemia
• Serum electrolyte levels: Hyponatremia indicates a poor prognosis.
• Kidney function tests: ↑ creatinine, ↓ sodium
• Urine analysis: to rule out concurrent renal impairment
• Fasting glucose: to screen for diabetes mellitus, which is a common comorbidity
• Fasting lipid profile: to detect dyslipidemia associated with a higher cardiovascular risk

Electrocardiogram (ECG)

ECG abnormalities in CHF are common, but are mostly nonspecific and nondiagnostic. ^[10]

• Signs of left ventricular hypertrophy ^[20]
  • ↑ QRS voltage (in the left chest leads and limb leads I and aVL): positive Sokolow-Lyon index
  • ↑ QRS duration (incomplete or complete left bundle branch block)
  • Left axis deviation
  • ST-T abnormalities (e.g., ST-depression)
  • P wave abnormalities (e.g., P-mitrale, biphasic P wave)
• Assessment of prior or concurrent heart conditions
  • Previous or acute MI (see “ECG changes in STEMI”)
  • Arrhythmias (e.g., atrial fibrillation, ventricular arrhythmias, sinus tachycardia or bradycardia, AV block)
• Signs of pericardial effusion and pericardial tamponade: low voltage ECG

Chest x-ray

Useful diagnostic tool to evaluate a patient with dyspnea and differentiate CHF from pulmonary disease

• Signs of cardiomegaly
  • Cardiothoracic width ratio > 0.5
  • Boot-shaped heart on PA view (due to right ventricular enlargement)
• Pulmonary congestion: See “X-ray findings in pulmonary congestion” for more information.

Transthoracic echocardiogram

Gold standard for evaluating patients with heart failure

• Assess ventricular function and hemodynamics
  • Atrial and ventricular size
  • Interventricular septum thickness: > 11 mm indicates cardiac hypertrophy.
  • Systolic function: left ventricular ejection fraction ^[21]
    • Normal EF: 50–70%
    • Borderline EF: 41–49%
    • Reduced EF: ≤ 40%
  • Diastolic function (diastolic filling, ventricle dilation)
• Investigate etiology
  • Valvular heart disease
  • Wall motion abnormalities (indicate prior or acute MI)
  • Right ventricular strain
  • Tissue Doppler: ↑ PCWP in left-sided heart failure

Other tests

• Cardiac stress test (exercise tolerance test): to assess the functional impairment due to CHF or other conditions (particularly CHD)
• Radionuclide ventriculography : indicated to assess left ventricular volume and ejection fraction (LVEF) ^[22]
• Cardiac MRI
  • Particularly useful for assessing cardiac morphology and function ^[23]
  • Cardiac size and volumes, wall thickness, valvular defects, wall motion abnormalities
• Coronary angiography (left heart catheterization): indicated to detect/confirm CHD and possible percutaneous coronary intervention
• Right heart catheterization ^[24]
  • If pulmonary hypertension is suspected, to assess the severity of systolic dysfunction, and/or to differentiate between types of shock
  • SvO₂ will be low in decompensated heart failure.
• Endomyocardial biopsy: may be performed if a specific diagnosis is suspected in patients with rapidly progressive clinical CHF or in case the results would alter the management of the patient (e.g., in amyloidosis) ^[25]

General measures ^[15]

• Lifestyle modifications
  • Salt restriction (< 3 g/day) in symptomatic patients
  • Fluid restriction in patients with edema and/or hyponatremia
  • Weight loss and exercise
  • Cessation of smoking and alcohol consumption
  • Immunization: pneumococcal vaccine and seasonal influenza vaccine
• Patient education
  • Self-monitoring and symptom recognition
  • Daily weight check: A weight gain > 2 kg within 3 days requires a doctor consult.
  • Monitoring of potential medication side effects (e.g., hypotension caused by ACE inhibitors, hyperkalemia caused by aldosterone-antagonists, sensitivity to sunlight caused by amiodarone)
  • Travel restrictions ^[26][27]
    • Include most recent medical record when traveling
    • Advise against traveling to destinations with limited access to or inadequate health care
    • Patients with acute heart failure should restrain from traveling
• Treatmenf of underlying conditions and contributing comorbidities

Pharmacologic treatment algorithm ^[28][29]

Drug	NYHA stages				Indications	Contraindications and important side effects	Benefits
	I	II	III	IV
First-line drugs
Diuretics	(✓)	(✓)	✓	✓	Begin treatment with loop diuretics (furosemide) to treat volume overload. Thiazides may be added for a synergistic effect.	Monitor for hypokalemia and hyponatremia, weight gain, and volume status.	Improve symptoms
ACE inhibitors	✓	✓	✓	✓	Initiate treatment with ACE inhibitors to reduce preload, afterload, and improve cardiac output. If the patient does not tolerate the drug (e.g., dry cough develops), substitute with an AT1-receptor blocker.	Monitor for hyperkalemia, hypotension, ↑ creatinine (renal impairment).	Improve symptoms and prognosis
Beta blockers	(✓)	✓	✓	✓	Add a beta blocker once the patient is stable on ACE inhibitors. Particularly beneficial for patients with hypertension and postmyocardial infarction	Contraindicated in acute decompensated heart failure
Aldosterone antagonists		(✓)	✓	✓	In select patients, an aldosterone antagonist may be beneficial. Patients with EF < 35% and after myocardial infarction Spironolactone; eplerenone as an alternative	Monitor for hyperkalemia.
Second-line drugs
Ivabradine		(✓)	(✓)	(✓)	If the highest tolerable dose of beta blocker is reached and the patient is still symptomatic or if the patient has a contraindication to beta blockers Patients with EF < 35% and a sinus rhythm with a resting heart rate > 70/min	Contraindicated in: Severe bradycardia Acute decompensated heart failure Severe hepatic dysfunction	Improves symptoms Reduces hospitalization rate
Hydralazine plus nitrate [30]			(✓)	(✓)	Patients with EF < 40% Particularly beneficial for African-American patients [31] Alternative if ACE inhibitors and AT1-receptor blockers are not tolerated	Monitor for volume depletion and hypotension.	Improve symptoms May improve prognosis
Digoxin [15]		(✓)	(✓)	(✓)	In heart failure with reduced ejection fraction If symptoms persist despite treatment with beta blockers, ACE inhibitors, diuretics, and aldosterone antagonists May be given to control ventricular rate in atrial fibrillation (if beta blockers are contraindicated)	Contraindicated in severe AV block	Improves symptoms Reduces hospitalization rate
Angiotensin receptor-neprilysin inhibitor	(✓)	(✓)	(✓)	(✓)	Persistent or worsening symptoms despite adequate treatment regimen with first-line drugs in patients with HFrEF Administered as valsartan-sacubitril combination: Valsartan is an AT1-receptor blocker, while sacubitril is a neprilysin inhibitor . Impaired breakdown of angiotensin II, substance P, and natriuretic peptides (e.g, BNP) → ↑ natriuresis, diuresis, and vasodilation → ↓ ECF	Elevated risk of angioedema if used in combination with ACE inhibitors Cough Dizziness, hypotension Hyperkalemia Progression of chronic renal disease (↑ creatinine)	Improves prognosis Reduces hospitalization rate
Nesiritide (BNP derivative)					Acute decompensated heart failure	Contraindicated in patients with hypotension and/or cardiogenic shock Adverse effects include hypotension and decrease in pulmonary capillary wedge pressure	Rarely used today due to side effects and longer half-life compared to other vasodilators (e.g., nitroglycerin)
(✓): see “Indications” column for detailed information

Drugs that improve prognosis are beta blockers, ACE inhibitors, and aldosterone antagonists.

Drugs that improve symptoms are diuretics and digoxin (significantly reduce the number of hospitalizations).

Conducting regular blood tests to assess electrolyte levels (potassium and sodium) is mandatory if the patient is on diuretics.

Contraindicated drugs ^[32][33]

• NSAIDs
  • Worsen renal perfusion
  • Reduce the effect of diuretics
  • May trigger acute cardiac decompensation
  • See “Nonsteroidal anti-inflammatory drugs.”
• Inhalation anesthetics
  • Induce myocardial depression and peripheral vasodilation
  • Decrease sympathetic activity
• Calcium channel blockers (verapamil and diltiazem)
  • Negative inotropic effect
  • Worsen symptoms and prognosis
• Thiazolidinediones
  • Promote the progression of CHF (↑ fluid retention and edema)
  • Increase the hospitalization rate
• Moxonidine: increases mortality in CHF with reduced ejection fraction (systolic dysfunction)
• Antidepressentans (citalopram): causes a dose-dependent QT prolongation

Avoid the concomitant use of calcium channel blockers with beta blockers.

Invasive procedures

• Implantable cardiac defibrillator (ICD): an implanted device that prevents sudden cardiac death by delivering electrical impulses to convert heart rhythm back into sinus rhythm
  • Primary prophylaxis indications ^[34]
    • Patients with ischemic heart disease and EF ≤ 30%
    • Heart failure NYHA class II–IV with EF ≤ 35%
    • Increased risk of life-threatening cardiac arrhythmias
  • Secondary prophylaxis indications
    • History of sudden cardiac arrest
    • Ventricular flutter or ventricular fibrillation ^[35]
• Cardiac resynchronization therapy (biventricular pacemaker): a three-chamber cardiac pacemakers used in symptomatic chronic heart failure to improve cardiac function
  • Indications ^[36]
    • Heart failure NYHA class II–IV with EF ≤ 35% ^[37]
    • Dilated cardiomyopathy
    • Left bundle branch block with QRS > 150 ms ^[38]
  • Can be combined with an ICD
• Coronary revascularization: may be used with PCTA or bypass surgery if CAD is present
• Valvular surgery: if valvular heart defects are present
• Ventricular assist devices
  • May be implanted to support ventricular function
  • May be indicated for temporary or long-term support (e.g., to bridge time until transplantation) of decompensated CHF
• Cardiac transplantation
  • Patients with end-stage CHF (NYHA class IV)
  • EF < 20%
  • No other viable treatment options