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 heart disease, diabetes mellitus, and hypertension. These conditions cause ventricular dysfunction with low cardiac output, which results in blood congestion (backward failure) and poor systemic perfusion (forward failure). CHF is classified as either left heart failure (LHF) or right heart failure (RHF), although biventricular (global) CHF is most commonly seen in clinical practice. LHF leads to pulmonary edema and resulting dyspnea, while RHF induces 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. Acute decompensated heart failure (ADHF) may occur as an exacerbation of CHF or be caused by an acute cardiac condition such as myocardial infarction. CHF is diagnosed based on clinical presentation and requires an initial workup to assess disease severity and 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. ADHF requires hospitalization and more intensive measures, such as hemodialysis.

• 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 and ejection fraction (EF)
• Diastolic dysfunction: CHF with reduced stroke volume and preserved ejection fraction
• Right heart failure (RHF): CHF due to right ventricular dysfunction; characterized by backward heart failure
• Left heart failure (LHF): CHF due to left ventricular dysfunction; characterized by forward heart failure
• Biventricular (global) CHF: CHF in which both the left and right ventricle are affected, resulting in simultaneous backward and forward CHF
• Chronic compensated CHF: clinically compensated CHF; the patient has signs of CHF on echocardiography but is asymptomatic or symptomatic and stable (see “Diagnostics” below)
• Acute decompensated CHF: sudden deterioration of CHF or new onset of severe CHF due to an acute cardiac condition (e.g., myocardial infarction)

References:^[1]

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

References:^[2][3]

Epidemiological data refers to the US, unless otherwise specified.

	Systolic dysfunction (reduced EF)	Diastolic dysfunction (preserved EF)
General causes	Coronary artery disease, myocardial infarction Arterial hypertension Valvular heart disease Diabetes mellitus (diabetic cardiomyopathy) Renal disease Infiltrative diseases (e.g., hemochromatosis, amyloidosis)
Specific causes	Cardiac arrhythmias Dilated cardiomyopathy (e.g., Chagas disease, chronic alcohol use, idiopathic) Myocarditis	Constrictive pericarditis Restrictive or hypertrophic cardiomyopathy Pericardial tamponade
Further risk factors	Obesity Smoking COPD Heavy drug (recreational and prescription) and 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.

References:^{[4][5][2][3][6][7]}

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 reduce ventricular contractility and stroke volume.
   • Increased afterload: increase in mean aortic pressure, outflow obstruction
   • Increased preload: ventricular volume overload
   • 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 → reduced ventricular filling and increased diastolic pressure → decreased cardiac output
   • Increased afterload; : increase in pulmonary artery pressure
   • Increased preload; : ventricular volume overload

Consequences of systolic and diastolic dysfunction

• Forward failure: reduced cardiac output → poor organ perfusion → organ dysfunction (e.g., hypotension, renal dysfunction)
• Backward failure
  • Increased left-ventricular volume and pressure → backup of blood into lungs → increased pulmonary capillary pressure → cardiogenic pulmonary edema
  • Reduced cardiac output → systemic venous congestion → edema and progressive congestion of internal organs
  • Resulting macroscopic findings: nutmeg liver

Compensation mechanisms

• Aim: maintain cardiac output if stroke volume is reduced
  • ↑ 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 → vasoconstriction → ↑ systemic blood pressure → ↑ afterload
      • Kidney: vasoconstriction of the efferent arterioles and, to a lesser degree, the afferent arterioles → ↓ net renal blood flow and ↑ intraglomerular pressure to maintain GFR
    • ↑ Aldosterone secretion → ↑ renal Na⁺ and H₂O resorption → ↑ preload
  • Brain natriuretic peptide (BNP): ventricular myocyte hormone released in response to increased ventricular filling and stretching
    • ↑ Intracellular smooth muscle cGMP → vasodilation → hypotension and decreased pulmonary capillary wedge pressure

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

References:^[4][8]

General features of heart failure
Nocturia [9] Fatigue Tachycardia, various arrhythmias Heart sounds: S3/S4 gallop Pulsus alternans
Clinical features of left-sided heart failure	Clinical features of right-sided heart failure
Pulmonary symptoms dominate	Symptoms of fluid retention (backward failure) dominate
Dyspnea , orthopnea Pulmonary edema in severe cases or acute decompensated heart failure (see below) Bilateral basilar rales may be audible on auscultation. Paroxysmal nocturnal dyspnea: nocturnal bouts of coughing and acute shortness of breath Cardiac asthma: increased pressure in the bronchial arteries results in airway compression, leading to bronchospasm [10] Laterally displaced apical heart beat (precordial palpation beyond the midclavicular line)	Peripheral pitting edema Signs of increased central venous pressure (CVP) Jugular venous distention: visible jugular venous congestion , also seen in biventricular heart failure Hepatojugular reflux: jugular venous congestion induced by exerting manual pressure over the patient's liver → ↑ volume load on the right side of the heart → right heart is unable to pump additional blood volume → visible jugular venous distention persists for several seconds Hepatic venous congestion Hepatosplenomegaly Abdominal pain Jaundice Ascites Congestion of other organs, e.g., congestive gastritis or gastropathy (nausea, loss of appetite), renal congestion
Forward failure: cool extremities, cerebral and renal dysfunction, sweating (NYHA IV)	Forward failure less pronounced

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

References:^{[4][5][11][12][13][14]}

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 demands of peripheral tissue oxygenation
• Etiology: conditions that lead to increased cardiac demand (high-output state)
  • Anemia
  • Systemic arteriovenous fistulas
  • Sepsis
  • Hyperthyroidism
  • Multiple myeloma
  • Glomerulonephritis
  • Polycythemia vera
  • Wet beriberi (vitamin B₁ deficiency)
  • Physiological causes: pregnancy, fever, exercise
• Clinical features
  • Symptoms of low-output CHF; particularly tachycardia, tachypnea, low blood pressure, and 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 (indicates rapid ventricular filling)
• Diagnostics
  • Primarily a clinical diagnosis
  • X-ray and echocardiography: cardiomegaly
• Therapy
  • Manage heart failure: symptom relief, hemodynamic stabilization
  • Treat underlying condition

References:^{[5][15][2][16]}

NYHA functional classification

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 (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 present at rest

American Heart Association (AHA) Classification (2013)

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, CAD, diabetes mellitus); no structural cardiac changes	No corresponding NYHA class
Stage B	Structural damage to the heart (e.g., infarct scars, dilatation, hypertrophy), without 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

References:^{[11][17][18][19][20][21]}

Heart failure is primarily a clinical diagnosis. Laboratory tests and imaging tests, including a chest x-ray and echocardiogram, are useful for evaluating the severity and cause of the condition.

Diagnostic approach ^[22]

1. Medical history, including pre-existing conditions and history of alcohol and recreational or 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 tool for assessing cardiac morphology and function, as well as investigating the underlying cause of CHF.
4. Other procedures (exercise testing, angiography) may be required for further investigation.

Initial evaluation ^[22]

Laboratory analysis

• Elevated BNP and NT-pro BNP
  • High levels of BNP in patients with classic symptoms of CHF confirm the diagnosis (high predictive index). ^[23]

	CHF unlikely	CHF likely
BNP (pg/mL)	< 100	> 500
NT-pro BNP (pg/mL)	< 300	> 450

• Elevated atrial natriuretic peptide (ANP):
• Complete blood count: may show anemia
• Serum electrolyte levels: hyponatremia → indicates a poor prognosis
• Kidney function tests: ↑ creatinine, ↓ sodium
• Urine analysis: 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.
• Signs of left ventricular hypertrophy
  • ↑ 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
• 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 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
  • Cardiac-to-thoracic width ratio > 0.5
  • Boot-shaped heart on PA view (due to left ventricular enlargement)
• Assess pulmonary congestion (see x-ray findings in pulmonary congestion)

Transthoracic echocardiogram

• Gold standard for evaluating patients with heart failure
• Assess ventricular function and hemodynamics
  • Atrial and ventricular size
  • Interventricular septum thickness: > 11 mm (normal 6–11 mm) indicates cardiac hypertrophy
  • Systolic function: left ventricular ejection fraction
    • Normal EF: > 55%
    • Reduced EF: 30–44%
    • Extremely reduced EF: < 30%
  • 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

Further 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)
• Cardiac MRI: particularly useful for assessing cardiac morphology and function
  • 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: 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

References:^{[4][11][2][24][12][25][26][27][28]}

General measures ^[22]

• Lifestyle modifications
  • Salt restriction (< 3 g/day)
  • 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
    • Weight gain > 2 kg within 3 days: consult the doctor
  • Monitoring of potential side effects (e.g., hypotension caused by ACE inhibitors, hyperkalemia caused by aldosterone-antagonists, sensitivity to sunlight caused by amiodarone)
• Treat any underlying conditions and contributing comorbidities.

Pharmacologic treatment algorithm

Drug	NYHA stages				Indications	Contraindications and important side effects	Benefits
	I	II	III	IV
First-line drugs
Diuretics (loop diuretics and thiazide 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 drug (e.g., dry cough develops) → substitute with AT2-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 inhibitor Particularly beneficial for patients with hypertension and post-myocardial infarction	Contraindicated in acute decompensated heart failure!
Aldosterone antagonists		(✓)	✓	✓	In select patients, an aldosterone antagonist may be beneficial. If 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-blocker use If EF < 35% and the patient has a sinus rhythm with a resting heart rate > 70/min	Contraindicated in severe bradycardia	Improves symptoms Reduces hospitalization rate
Hydralazine plus nitrate			(✓)	(✓)	If EF < 40%; particularly beneficial for African-American patients Alternative if ACE inhibitors and AT1 blockers are not tolerated	Monitor for volume depletion and hypotension	Improves symptoms; may improve prognosis
Digoxin		(✓)	(✓)	(✓)	In heart failure with reduced ejection fraction If symptoms persist despite treatment with beta blocker, ACE inhibitor, 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
ARNI (angiotensin receptor-neprilysin inhibitor)	(✓)	(✓)	(✓)	(✓)	Persistent or worsening symptoms despite adequate treatment regimen with first-line drugs Administered as combination valsartan-sacubitril	Angioedema, hypotension, hyperkalemia, and progression of chronic renal disease (↑ creatinine)	Improves prognosis Reduces hospitalization rate
Nesiritide (BNP derivative)					Acute decompensated heart failure Rarely used today due to side effects and longer half-life compared to other vasodilators (e.g., nitroglycerin)	Contraindicated in patients with hypotension and/or cardiogenic shock Adverse effects include hypotension and decrease in pulmonary capillary wedge pressure
(✓): see “Indications” column for detailed information

Drugs that improve prognosis: beta blockers, ACE inhibitors, and aldosterone antagonists!

Drugs that improve symptoms: 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

• NSAIDs
  • Worsen renal perfusion (see “Side effects” of NSAIDs)
  • Reduce the effect of diuretics
  • May trigger acute cardiac decompensation
• Calcium channel blockers (verapamil and diltiazem): negative inotropic effect; worsen symptoms and prognosis
• Thiazolidinediones: promote the progression of CHF (↑ fluid retention and edema) and increase the hospitalization rate
• Moxonidine: increases mortality in CHF with reduced ejection fraction (systolic dysfunction)

Invasive procedures

• Implantable cardiac defibrillator (ICD): prevents sudden cardiac death
  • Primary prophylaxis indications
    • CHF with EF < 35% and prior myocardial infarction/CHD
    • Increased risk of life-threatening cardiac arrhythmias
  • Secondary prophylaxis indications: history of sudden cardiac arrest, ventricular flutter, or ventricular fibrillation
• Cardiac resynchronization therapy (biventricular pacemaker): improves cardiac function
  • Indications: CHF with EF < 35%, dilated cardiomyopathy, and left bundle branch block
  • Can be combined with an ICD
• Coronary revascularization with PCTA or bypass surgery may be indicated 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: for patients with end-stage CHF (NYHA class IV), ejection fraction < 20%, and no other viable treatment options

References:^{[2][29][17][30][31][32][33][34]}