Congestive heart failure

Congestive heart failure (CHF) is a clinical syndrome in which the heart is unable to pump enough blood to meet the metabolic needs of the body. The three main causes of heart failure are coronary heart disease, diabetes mellitus, and hypertension. These conditions cause ventricular dysfunction with low cardiac output, which in turn results in congestion of blood (backward failure) and poor systemic perfusion (forward failure). Heart failure is commonly classified as left-sided and right-sided heart failure, although biventricular heart failure is most commonly seen in clinical practice. Left-sided heart failure results in pulmonary edema and associated dyspnea, while right-sided heart failure induces systemic venous congestion that causes symptoms such as pitting edema and hepatomegaly. Biventricular (global) HF presents with clinical features of both left-sided and right-sided failure, as well as general symptoms such as tachycardia, fatigue, and nocturia. In rare cases, high-output HF may occur as a result of conditions with an increased (rather than decreased) cardiac output, which overwhelms the heart. Acute decompensated heart failure (ADHF) may occur as an exacerbation of CHF or be due to an acute cardiac condition such as myocardial infarction. The diagnosis of CHF is based on clinical presentation and requires an initial workup to assess disease severity and possible causes. The initial workup includes measurement of brain natriuretic peptide levels, chest x-ray, and ECG. Management of CHF includes lifestyle modifications, treatment of associated conditions (e.g., hypertension) and comorbidities (e.g., anemia) that would otherwise worsen the symptoms of HF, and additional pharmacologic agents that reduce the workload of the heart. ADHF requires hospitalization and more intensive measures, such as hemodialysis.

• Heart failure (HF): 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: heart failure with reduced stroke volume and ejection fraction
• Diastolic dysfunction: heart failure with reduced stroke volume and preserved ejection fraction
• Right-sided HF: heart failure due to right ventricular dysfunction; characterized by backward heart failure
• Left-sided HF: heart failure due to left ventricular dysfunction; characterized by forward heart failure
• Biventricular HF: heart failure in which both the left and right ventricle are affected, resulting in backward and forward heart failure
• Chronic compensated HF: heart failure that is clinically compensated; the patient is asymptomatic or symptomatic and stable, with echocardiographic signs of HF (see “Diagnostics” below)
• Acute decompensated HF: sudden deterioration of chronic HF or new onset of severe HF 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 have heart failure)
    • The incidence is higher among African Americans, Hispanics, and Native Americans
  • Increases with age; ∼ 10% of individuals > 60 years old affected
  • Systolic heart disease is the most common form of HF overall.

References:^[2][3]

Epidemiological data refers to the US, unless otherwise specified.

	Systolic dysfunction	Diastolic dysfunction
General causes	Coronary artery disease, myocardial infarction Arterial hypertension Diabetes mellitus Valvular disease
Specific causes	Cardiac arrhythmias Cardiomyopathy (e.g., Chagas disease) Myocarditis	Constrictive pericarditis Restrictive or hypertrophic cardiomyopathy Pericardial tamponade
Further risk factors	Obesity Smoking COPD Hemochromatosis 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 HF!
References:^{[4][5][2][3][6]}

General physiological concepts

• Cardiac output is determined by:
  • Preload
  • Afterload
  • Ventricular contractility

Pathomechanism

• Underlying pathomechanism of reduced cardiac output
  1. Systolic ventricular dysfunction (most common) due to:
     • Reduced contractility: Damage and loss of myocytes reduces 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 to 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][7]

General features of heart failure
Nocturia 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 Cardiac asthma 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: induced jugular venous congestion 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 Hepatomegaly 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][8][9][10][11]}

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 an increased cardiac demand (high-output state)
  • Anemia
  • Systemic arteriovenous fistulas
  • Sepsis
  • Hyperthyroidism
  • Multiple myeloma
  • Glomerulonephritis
  • Polycythemia vera
  • Wet beriberi (vitamin B₁ deficiency)
  • Carcinoid syndrome
  • Physiological causes: pregnancy, fever, exercise
• Clinical features
  • Symptoms of low-output HF; 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][12][2][13]}

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

1. Medical history, including pre-existing conditions and history of alcohol and recreational or prescribed drug abuse
2. Initial evaluation involves laboratory tests 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 HF.
4. Other procedures (exercise testing, angiography) may be required for further investigation.

Initial evaluation

Laboratory analysis

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

	HF unlikely	HF likely
BNP (pg/mL)	< 100	> 400
NT-pro BNP (pg/mL)	< 300	> 450 (patients aged < 50 years) > 900 (patients aged 50–75 years) > 1800 (patients aged > 75 years)

• Elevated atrial natriuretic peptide (ANP):
• Complete blood count
  • Serum electrolyte levels: hyponatremia → indicates a poor prognosis
  • Kidney function tests (↑ creatinine, ↓ sodium)
  • Leukocytes and CRP (to rule out infection)
  • Hemoglobin and ferritin (to rule out anemia)
• Urine analysis: rule out concurrent renal impairment
• Investigate causative factors and common comorbidities

Electrocardiogram (ECG)

• ECG abnormalities in HF 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
  • ST-T abnormalities (e.g., ST-depression)
  • P wave abnormalities (P-mitrale, biphasic P wave)
• Assessment of prior or concurrent heart conditions
  • Previous or acute MI: pathological Q waves or loss of R waves (poor R wave progression); evidence of a prior myocardial infarction
  • 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 HF 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 in “Acute decompensated heart failure” below.)

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%
    • Slightly reduced EF: 45–54%
    • 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

Ultrasound

• • Ultrasound of pleural cavities: sensitive method for detecting pleural effusion (CT may be better for detecting small amounts of fluid)
  • Ultrasound of large blood vessels
    • The volume status of the inferior vena cava is used to assess intravascular volume
    • Normal IVC diameter is < 2 cm. It is more important to determine its variation during respiration and the dynamics of the volume status after initiating diuretic treatment, rather than comparing it with normal values.
  • Ultrasound of the abdomen
    • Assess congestive hepatopathy
    • Assess the renal and urinary tract in patients with renal dysfunction or reduced diuresis to rule out postrenal causes. (e.g., kidney stones, urinary retention)

Further tests

• Cardiac stress test (exercise tolerance test) to assess the functional impairment due to HF 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

References:^{[4][8][2][19][9][20][21][22][23]}

General measures

• 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 potential side effects (e.g., hypotension caused by ACE inhibitors, hyperkalemia caused by aldosterone-antagonists, sensitivity to sunlight caused by amiodarone)
  • Travel restrictions: Include most recent medical record when traveling. Advise against traveling to destinations with limited access to or inadequate health care.
  • Patients suffering from symptoms of depression and cognitive dysfunction should also be offered neurological and psychiatric treatment.
• 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 (e.g., dry cough occurs) → substitute with 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 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		(✓)	(✓)	(✓)	May be given in combination with beta blocker 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; and may improve prognosis
Digoxin		(✓)	(✓)	(✓)	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
Nesiritide					Rarely used in patients with CHF 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 inlcude hypotension and decrease in pulmonary capillary wedge pressure

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 HF (↑ fluid retention and edema) and increase the hospitalization rate
• Moxonidine: increases mortality in HF with reduced ejection fraction (systolic dysfunction)
• Trimethoprim-sulfamethoxazole
  • Trimethoprim causes hyperkalemia and inhibits the renal tubular creatinine secretion (→ reduced creatinine clearance).
  • Significantly delayed excretion in chronic renal disease

Invasive procedures

• Implantable cardiac defibrillator: (ICD): prevents sudden cardiac death
  • Primary prophylaxis indications
    • HF 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: (CRT): improves cardiac function
  • Indications: HF with EF < 35% and left bundle branch block (intraventricular conduction delay with QRS > 120–150 ms)
  • Can be combined with an ICD
• Coronary revascularization with PCTA or bypass surgery may be indicated if CHD is present
• Valvular surgery if valvular heart defects are present
• Ventricular assist devices: (left-ventricular assist devices, right-ventricular assist devices, or biventricular assist devices): a device that 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 HF
• Cardiac transplantation: for patients with end-stage HF (NYHA class IV), ejection fraction < 20%, and no other viable treatment options

References:^{[2][24][14][25][26][27][28][29]}