What is the pathophysiology of heart failure (HF)?

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From the Guidelines

Heart failure is a complex syndrome characterized by the heart's inability to pump enough blood to meet the body's needs, resulting from an initial injury or stress that triggers compensatory mechanisms, including activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS), which eventually become harmful 1.

Pathophysiology of Heart Failure

The pathophysiology of heart failure involves a series of complex processes, including:

  • Cardiac remodeling, where the ventricles dilate and hypertrophy in an attempt to maintain stroke volume 1
  • Neurohormonal activation, leading to vasoconstriction, sodium and water retention, and increased afterload 1
  • Chronic sympathetic stimulation, causing myocyte damage and fibrosis 1
  • Inflammatory cytokines and oxidative stress, contributing to myocardial damage 1
  • A shift from efficient aerobic metabolism to less efficient anaerobic pathways in the failing heart 1

Stages of Heart Failure

The development of heart failure can be characterized by considering four stages of the disease, as described in the Introduction, which recognizes that heart failure has established risk factors and structural prerequisites, and that specific treatments targeted at each stage can reduce the morbidity and mortality of heart failure 1.

Clinical Presentation

The clinical presentation of heart failure is characterized by symptoms such as dyspnea, fatigue, and fluid accumulation in the lungs and periphery, resulting from the heart's inability to pump enough blood to meet the body's needs 1.

Management

The management of heart failure involves a comprehensive approach, including symptom improvement, reducing congestion with diuretics, and treating cardiovascular and non-cardiovascular comorbidities, as well as the use of disease-modifying therapies, such as sodium-glucose co-transporter 2 (SGLT2) inhibitors, which have been shown to reduce composite of cardiovascular death or heart failure hospitalizations in patients with heart failure with preserved ejection fraction (HFpEF) 1.

From the Research

Pathophysiology of Heart Failure

The pathophysiology of heart failure is a complex and multifactorial process, involving various mechanisms that contribute to the development and progression of the disease. Some of the key mechanisms include:

  • Activation of neurohormonal pathways, such as the sympathoadrenergic and renin-angiotensin-aldosterone systems, which lead to adaptive mechanisms and volume overload 2, 3
  • Cellular, structural, and molecular modulations that affect cardiac function and phenotype 3
  • Ventricular remodeling, which can lead to increased ventricular volume and wall thickness 4
  • Activation of inflammatory mediators, which can promote ventricular remodeling and vascular dysfunction 5

Clinical Presentation and Diagnosis

The clinical presentation of heart failure can vary, but common symptoms include:

  • Dyspnea and pulmonary congestion 4, 3
  • Peripheral edema and ascites 4
  • Fatigue, nausea, and lack of appetite 4
  • Diagnosis is often made using a combination of noninvasive and invasive diagnostic procedures, including echocardiography, NMR, and heart catheterization 3

Treatment and Management

Treatment strategies for heart failure aim to slow disease progression and improve symptoms, and may include:

  • Pharmacological therapy, such as beta-blockers, ACE-inhibitors, and ARNI 3
  • Interventional and surgical therapy options, such as ventricular resynchronization therapy and heart transplantation 4, 3
  • Modulation of activated systems to improve outcome and symptoms in patients with left ventricular dysfunction 3

Underlying Mechanisms and Progression

The underlying mechanisms of heart failure involve a complex interplay between various organ systems, including the kidney and the cardiovascular system 6. The disease can progress from an asymptomatic state to symptomatic heart failure, with multi-organ congestion, fibrosis, and decompensation 6. Understanding the pathophysiology of heart failure is essential for initiating adequate therapeutic options and preventing disease progression 3, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pathophysiology of Heart Failure.

Comprehensive Physiology, 2015

Research

Pathophysiology of heart failure.

Cardiovascular diagnosis and therapy, 2021

Research

The pathophysiology of heart failure.

Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology, 2012

Research

Pathophysiology and the cardiorenal connection in heart failure. Circulating hormones: biomarkers or mediators.

Clinica chimica acta; international journal of clinical chemistry, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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