Congestive heart failure pathophysiology

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Congestive Heart Failure Microchapters


Patient Information


Historical Perspective



Systolic Dysfunction
Diastolic Dysfunction


Differentiating Congestive heart failure from other Diseases

Epidemiology and Demographics

Risk Factors


Natural History, Complications and Prognosis


Clinical Assessment

History and Symptoms

Physical Examination

Laboratory Findings


Chest X Ray

Cardiac MRI


Exercise Stress Test

Myocardial Viability Studies

Cardiac Catheterization

Other Imaging Studies

Other Diagnostic Studies


Invasive Hemodynamic Monitoring

Medical Therapy:

Acute Pharmacotherapy
Chronic Pharmacotherapy in HFpEF
Chronic Pharmacotherapy in HFrEF
ACE Inhibitors
Angiotensin receptor blockers
Aldosterone Antagonists
Beta Blockers
Ca Channel Blockers
Positive Inotropics
Angiotensin Receptor-Neprilysin Inhibitor
Antiarrhythmic Drugs
Nutritional Supplements
Hormonal Therapies
Drugs to Avoid
Drug Interactions
Treatment of underlying causes
Associated conditions

Exercise Training

Surgical Therapy:

Biventricular Pacing or Cardiac Resynchronization Therapy (CRT)
Implantation of Intracardiac Defibrillator
Cardiac Surgery
Left Ventricular Assist Devices (LVADs)
Cardiac Transplantation

ACC/AHA Guideline Recommendations

Initial and Serial Evaluation of the HF Patient
Hospitalized Patient
Patients With a Prior MI
Sudden Cardiac Death Prevention
Surgical/Percutaneous/Transcather Interventional Treatments of HF
Patients at high risk for developing heart failure (Stage A)
Patients with cardiac structural abnormalities or remodeling who have not developed heart failure symptoms (Stage B)
Patients with current or prior symptoms of heart failure (Stage C)
Patients with refractory end-stage heart failure (Stage D)
Coordinating Care for Patients With Chronic HF
Quality Metrics/Performance Measures

Implementation of Practice Guidelines

Congestive heart failure end-of-life considerations

Specific Groups:

Special Populations
Patients who have concomitant disorders
Obstructive Sleep Apnea in the Patient with CHF
NSTEMI with Heart Failure and Cardiogenic Shock

Congestive heart failure pathophysiology On the Web

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CDC on Congestive heart failure pathophysiology

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Risk calculators and risk factors for Congestive heart failure pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Saleh El Dassouki, M.D [3]; Atif Mohammad, MD


Heart failure is a complex syndrome whereby there is inadequate output of the heart to meet the metabolic demands of the body. Heart failure is caused by abnormal function of different anatomic parts of the heart including the pericardium, the myocardium, the endocardium, the heart valves and the great vessels. Heart failure is characterized by decreased cardiac output but not necessarily decreased ejection fraction. Symptoms of heart failure are due to a lack of both forward blood flow to the body, and backward flow into the lungs. The body tries to compensate for the low cardiac output by mechanisms that increase the preload and afterload. These mechanisms lead to exacerbation of the cardiac malfunction and symptoms associated with heart failure.


Decreased Cardiac Output

Underlying Cardiac Abnormalities Leading to Heart Failure

Heart failure may result from an abnormality or dysfunction of any one of the anatomical structures of the heart:

Systolic versus Diastolic Dysfunction

Systolic Dysfunction

Shown below is an image summarizing the pathophysiology of systolic heart failure.
Systolic heart failure.
Systolic heart failure.

Diastolic Dysfunction

  • Heart failure caused by diastolic dysfunction is generally described as the failure of the ventricular chambers to adequately relax and results from stiffening of the ventricular walls. The consequence is reduced filling of chambers of the heart.
  • The failure of ventricular relaxation also results in elevated end-diastolic pressures, and the end result is identical to the case of systolic dysfunction (pulmonary edema in left heart failure, peripheral edema in right heart failure.)
  • Diastolic dysfunction can be caused by processes similar to those that cause systolic dysfunction, particularly causes that affect cardiac remodeling.
  • Diastolic dysfunction typically becomes symptomatic in physiological conditions under which a high cardiac demand is required. Therefore, patients suffering from diastolic dysfunction are sensitive to increases in heart rate, and sudden bouts of tachycardia (which can be caused simply by physiological responses to exertion, fever, or dehydration, or by pathological tachyarrhythmias such as atrial fibrillation with rapid ventricular response) which may result in flash pulmonary edema.
  • Adequate rate control (usually with a pharmacological agent that slows down atrioventricular node conduction such as a calcium channel blocker or a beta-blocker) is therefore key to preventing decompensation.
  • Left ventricular diastolic function can be determined through echocardiography by measurement of various parameters such as the E/A ratio (early-to-atrial left ventricular filling ratio), the E (early left ventricular filling) deceleration time, and the isovolumetric relaxation time.

Manifestations of Heart Failure

Pulmonary Edema



The reduction in forward cardiac output leads to hypoperfusion at rest which manifests as:

Impaired Cardiac Reserve

As the heart works harder to meet normal metabolic demands, the amount cardiac output can increase in times of increased oxygen demand (e.g. exercise) is reduced. This contributes to the exercise intolerance commonly seen in heart failure. This translates to the loss of one's cardiac reserve. The cardiac reserve refers to the ability of the heart to work harder during exercise or strenuous activity. Since the heart has to work harder to meet the normal metabolic demands, it is incapable of meeting the metabolic demands of the body during exercise.

Compensatory Mechanisms and Their Associated Complications

Shown below is an image summarizing the compensatory mechanisms of the heart along with their associated complications.
The compensatory mechanisms in heart failure.
The compensatory mechanisms in heart failure.
  1. Dilation of the left ventricle to increase the stroke volume and
  2. Increase in heart rate

Dilatation of the Left Ventricle:

Hypertrophy of the Myocardium:

  • Hypertrophy (an increase in physical size) of the myocardium can develop, which is caused by the terminally differentiated heart muscle fibers increasing in size in an attempt to improve contractility. This may contribute to the increased stiffness and decreased ability to relax during diastole.

Activation of the Sympathetic Nervous System:

  • Arterial blood pressure falls. This destimulates baroreceptors in the carotid sinus and aortic arch which link to the nucleus tractus solitarius. This center in the brain increases sympathetic activity, releasing catecholamines into the blood stream. Binding to alpha-1 receptors results in systemic arterial vasoconstriction. This helps restore blood pressure but also increases the total peripheral resistance, increasing the workload of the heart. Binding to beta-1 receptors in the myocardium increases the heart rate and make contractions more forceful, in an attempt to increase cardiac output. This also, however, increases the amount of work the heart has to perform.
  • The increased heart rate, stimulated by increased sympathetic activity[3] maintains cardiac output. Initially, this helps compensate for heart failure by maintaining blood pressure and perfusion, but places further strain on the myocardium, increasing coronary perfusion requirements, which can lead to worsening of ischemic heart disease. Sympathetic activity may also cause potentially fatal arrhythmias.
  • Increased sympathetic stimulation also causes the hypothalamus to secrete vasopressin (also known as antidiuretic hormone or ADH), which causes free water retention in the kidneys leading to hyponatremia. This free water retention increases total body blood volume and blood pressure.

Stimulation of the Renal / Adrenal / Sympathetic Axis:

  • Reduced perfusion (blood flow) to the kidneys stimulates the release of renin – an enzyme which catalyses the production of the potent vasopressor angiotensin. Angiotensin and its metabolites cause further vasocontriction, and stimulate increased secretion of the steroid aldosterone from the adrenal glands. This promotes salt and fluid retention at the kidneys, also increasing the blood volume.
  • The chronically high levels of circulating neuroendocrine hormones such as catecholamines, renin, angiotensin, and aldosterone affects the myocardium directly, causing structural remodelling of the heart over the long term. Many of these remodelling effects seem to be mediated by transforming growth factor beta (TGF-beta), which is a common downstream target of the signal transduction cascade initiated by catecholamines[4] and angiotensin II,[5] and also by epidermal growth factor (EGF), which is a target of the signaling pathway activated by aldosterone[6]
  • The increased peripheral resistance and greater blood volume place further strain on the heart and accelerates the process of damage to the myocardium. Vasoconstriction and fluid retention produce an increased hydrostatic pressure in the capillaries. This shifts the balance of forces in favour of interstitial fluid formation as the increased pressure forces additional fluid out of the blood, into the tissue. This results in edema (fluid build-up) in the tissues. In right-sided heart failure this commonly starts in the ankles where venous pressure is high due to the effects of gravity (although if the patient is bed-ridden, fluid accumulation may begin in the sacral region.) It may also occur in the abdominal cavity, where the fluid build-up is called ascites. In left-sided heart failure edema can occur in the lungs - this is called cardiogenic pulmonary edema. This reduces spare capacity for ventilation, causes stiffening of the lungs and reduces the efficiency of gas exchange by increasing the distance between the air and the blood. The consequences of this are shortness of breath, orthopnea and paroxysmal nocturnal dyspnea.

Right Heart Failure as a Result of Left Heart Failure

  • The hypoxia caused by pulmonary edema causes vasoconstriction in the pulmonary circulation, which results in pulmonary hypertension. Since the right ventricle generates far lower pressures than the left ventricle (approximately 20 mmHg versus around 120 mmHg, respectively, in the healthy individual) but nonetheless generates cardiac output exactly equal to the left ventricle, this means that a small increase in pulmonary vascular resistance causes a large increase in amount of work the right ventricle must perform.
  • Other mechanisms of right heart failure are mediated by neurohormonal activation.[7]
  • Mechanical effects may also contribute. As the left ventricle distends, the intraventricular septum bows into the right ventricle, decreasing the filling capacity of the right ventricle.

Microscopic Pathology

Images courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology


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  2. Boron and Boulpaep 2005 Medical Physiology Updated Edition p533 ISBN 0-7216-3256-4
  3. Rang HP (2003). Pharmacology. Edinburgh: Churchill Livingstone. p. 127. ISBN 0-443-07145-4.
  4. Shigeyama J, Yasumura Y, Sakamoto A; et al. (2005). "Increased gene expression of collagen Types I and III is inhibited by beta-receptor blockade in patients with dilated cardiomyopathy". Eur. Heart J. 26 (24): 2698–705. doi:10.1093/eurheartj/ehi492. PMID 16204268. Unknown parameter |month= ignored (help)
  5. Tsutsui H, Matsushima S, Kinugawa S; et al. (2007). "Angiotensin II type 1 receptor blocker attenuates myocardial remodeling and preserves diastolic function in diabetic heart" (– Scholar search). Hypertens. Res. 30 (5): 439–49. doi:10.1291/hypres.30.439. PMID 17587756. Unknown parameter |month= ignored (help)[dead link]
  6. Krug AW, Grossmann C, Schuster C; et al. (2003). "Aldosterone stimulates epidermal growth factor receptor expression". J. Biol. Chem. 278 (44): 43060–6. doi:10.1074/jbc.M308134200. PMID 12939263. Unknown parameter |month= ignored (help)
  7. Hunter JG, Boon NA, Davidson S, Colledge NR, Walker B (2006). Davidson's principles & practice of medicine. Elsevier/Churchill Livingstone. p. 544. ISBN 0-443-10057-8.

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