Heart Failure - Chronic Disease Background

Introduction

Heart failure is a clinical syndrome due to a structural and/or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood in order to deliver oxygen (O₂) at a rate commensurate with the requirements of the metabolizing tissues in spite of normal filling pressures or only at the expense of elevated filling pressures. It is corroborated by the objective evidence of cardiogenic, pulmonary, and/or systemic congestion and/or elevated levels of natriuretic peptides.  

The symptoms of heart failure are caused by ventricular dysfunction secondary to abnormalities of the myocardium, pericardium, endocardium, valves, or heart rhythm or conduction. 

Epidemiology

The incidence of heart failure increases with age with a higher increase in females as compared to males. The prevalence rate in adults is 1-3% or approximately 64 million, with prevalence increasing with age. The prevalence rate in patients <55 years old is approximately 1% and >10% in patients ≥70 years old.  

The prevalence rates are higher in North Africa, Central Europe, and the Middle East, and lowest in Eastern Europe and Southeast Asia. The lifetime risk of developing heart failure is approximately 20% in individuals >40 years of age. Among the phenotypes, heart failure with reduced ejection fraction remains to be the most common overall. Heart failure is also expected to increase largely due to the collective effects of increasing risk factors and comorbidities. 
 
According to the China Hypertension Survey in 2012-2015, the estimated prevalence of heart failure was 1.3% affecting approximately 14 million Chinese aged ≥35 years old. The country’s crude in-hospital mortality was 4.1%. In Taiwan, the prevalence of heart failure was estimated at 6% with approximately 2.2% or 40,000 hospitalizations per year.  In Hong Kong, the prevalence rate was 2-3%. The Korean Society of Heart Failure reported that there was an increasing prevalence of the disease at 0.8% in 2002, 1.5% in 2013, and 2.2% in 2018. The age-adjusted incidence decreased by 20% from 693 in 2004 to 554 per 100,000 population in 2018. The overall mortality rate likewise increased from 39 in 2004 to 245 per 100,000 population in 2018.

Heart failure among Asians generally occurs at a younger age relative to Western countries. Despite improvement in heart failure management, the crude mortality among Asians remains high and was estimated to be 9.6% among symptomatic patients. 

Pathophysiology

Heart failure results from systolic dysfunction due to impaired cardiac contractility, and diastolic dysfunction due to impaired ventricular relaxation and compliance which limit effective cardiac filling.

Cardiac injury stimulates cellular, structural, and neurohumoral modulations influencing cell function leading to activation of the sympathoadrenergic and renin-angiotensin-aldosterone system (RAAS) and resulting to adaptive mechanisms accompanied by volume overload, tachycardia, dyspnea, and further deterioration of the cellular function.  

Catecholamines increase intracellular calcium thereby increasing contractility but increases myocardial O₂ demand in the long run which can lead to life-threatening arrhythmias and activation of signaling pathways of hypertrophy and cell death resulting to further cardiac function deterioration. Permanent activation of the neurohumoral system also affects cell expression and cell function (eg stretch-induced force generation, frequency-induced force generation, interstitial and structural cell-interaction).  

Heart Failure with Preserved Ejection Fraction

Heart failure with preserved ejection fraction is characterized by impaired left ventricular relaxation and/or filling, increased ventricular stiffness, and elevated filling pressure (left ventricular end-diastolic pressure) accompanied by pressure overload. Structural and cellular changes (eg alteration of cardiomyocyte relaxation and inflammation, cardiomyocyte hypertrophy, intercellular fibrosis) cause the inability of the left ventricles to relax properly. The impairment of myocardial relaxation leads to reduced rate and amount of early diastolic left ventricular filling resulting to shifting of left ventricular filling to late diastole with atrial contraction making an important contribution to left ventricular filling.  

Alteration of left ventricular diastolic function leads to decreased left ventricular chamber distensibility and increased diastolic pressure at any given left ventricular volume. It is associated with structural remodeling affecting the left ventricle and left atrium, right ventricle, cardiomyocytes, and extracellular matrix.  

Heart Failure with Reduced Ejection Fraction

In heart failure with reduced ejection fraction, there is reduced cardiac output due to depressed myocardial contractility. Heart failure with reduced ejection fraction occurs when there is a substantial acute or chronic cardiomyocyte loss after myocardial infarction, genetic mutation, myocarditis, or valvular disease with cell death due to overload that leads to systolic dysfunction development. The major structural change is eccentric remodeling accompanied by chamber dilatation and volume overload resulting to forward failure. Volume overload results from permanent neurohumoral activation.  

Systolic dysfunction triggers neurohumoral activation and cardiac remodeling causing increased sympathetic activity which restores cardiac output by increasing contractility and heart rate. The reduced cardiac output also stimulates salt and water retention causing blood volume expansion leading to increased end-diastolic pressure and volume.  

Etiology

The following are the common causes of heart failure: 

• Cardiac pathologies (eg coronary artery disease [CAD], cardiomyopathies, congenital heart disease, tachyarrhythmia, valvular heart disease)
• Hypertension
• Infiltrative cardiac disease (eg amyloid, hemochromatosis, hypereosinophilic syndrome, sarcoid)
• Infections (eg rheumatic fever, sexually transmitted diseases, pneumonia)
• Endocrine disorders (eg diabetes, dyslipidemia, hypo- or hyperthyroidism, adrenal disorder, pheochromocytoma)
• Nutritional disorders (eg deficiency of thiamine, selenium, iron, calcium, phosphates and L-carnitine, obesity, cachexia)
• Toxins (eg alcohol, medications, trace elements, radiotherapy, illicit drug use [eg cocaine, cannabis, methamphetamine])
• Drugs (eg beta-blocker eye drops, calcium antagonists, antiarrhythmics, cardiotoxic chemotherapy agents, nonsteroidal anti-inflammatory drugs [NSAIDs], Clozapine, non-compliance to medications)
• Other diseases (eg collagen vascular disease, inflammatory or immunological diseases, neuromuscular disease, storage disorders, malignancies, severe anemia, renal dysfunction, renal artery stenosis, and end-stage renal failure)

Causes of heart failure with reduced ejection fraction include:

• Ischemic heart disease
• Hypertension
• Arrhythmias
• Abnormal cardiac conduction
• Congenital heart disease
• Valvular heart disease
• Cardiomyopathy
• Infectious/inflammatory disease
• Drug- and chemotherapy-related causes
• Genetic
• Storage/infiltrative disease

Risk Factors

Risk factors for heart failure with preserved ejection fraction include:

• Ischemic heart disease
• Atrial fibrillation
• Valvular heart disease
• Hypertension
• Type 2 diabetes
• Obesity
• Chronic kidney disease (CKD)
• Pulmonary disease
• Sleep apnea
• Anemia
• Inflammatory/infiltrative disease
• Female sex
• Advanced age
• Sedentary lifestyle

Classification

Types of Heart Failure  

Heart Failure Based on Time-course  

Acute heart failure¹ refers to the first occurrence (new-onset or de novo) of heart failure that may result from the deterioration of a previously stable heart failure.  

Chronic heart failure refers to a chronic state where the patient’s signs and symptoms have been unchanged (stable) for at least a month. The condition may decompensate suddenly or slowly when stable chronic heart failure deteriorates leading to hospitalization or outpatient intravenous diuretic therapy.  

Congestive heart failure refers to acute heart failure or chronic heart failure that has evidence of volume overload.  

Transient heart failure refers to symptomatic heart failure over a limited period, although long-term therapy may be indicated. Transient heart failure may be recurrent or episodic.  

Heart Failure Based on Left Ventricular Ejection Fraction 

Heart failure with preserved ejection fraction (diastolic heart failure) is defined as having preserved systolic function and a left ventricular ejection fraction that is defined as ≥50%. The condition is not due to hypertrophic or infiltrative cardiomyopathy, high-output heart failure, or pericardial or valvular disease. Further criteria for the diagnosis of heart failure with preserved ejection fraction include the presence of current or  prior heart failure symptoms and/or signs, and elevated levels of natriuretic peptides with at least one added criterion of either significant structural heart disease or diastolic dysfunction.

Heart failure with reduced ejection fraction (systolic heart failure) is defined as a left ventricular ejection fraction of <50%. Heart failure with mildly reduced ejection fraction is the traditional term for heart failure in patients with a left ventricular ejection fraction of 41-49%, representing a “grey area” between heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. 

Heart failure with non-reduced ejection fraction, defined as signs and symptoms of heart failure with a left ventricular ejection fraction of >40%, is a unified term that consolidates heart failure with mildly reduced ejection fraction and heart failure with preserved ejection fraction.  

Lastly, heart failure with improved ejection fraction is characterized by a history of heart failure with reduced ejection fraction whose left ventricular ejection fraction has increased by ≥10% to a new left ventricular ejection fraction of >40%.  

¹In the 2026 European Society of Cardiology (ESC) guidelines, decompensated heart failure replaces acute heart failure, but acute heart failure is retained in this disease management chart to maintain consistency with other international guidelines and published clinical literature. 

Chronic Heart Failure Classification Based on Duration Since Last Admission  

This classification helps optimize guideline-directed medical therapy and is categorized according to the following phases:

• C1 for Optimization Phase which includes patients who are recently diagnosed with heart failure and not on optimal guideline-directed medical therapy
• C2 for Remission Phase which includes patients with no hospitalization for heart failure for >6 months and the patient is with optimal medical therapy
• C3 for Vulnerable Phase which includes patients with recent hospitalization within 6 months but not within 30 days
• C4 for Transition Phase which includes patients with recent hospitalization within 30 days

Development Stages of Heart Failure  

The development stages of heart failure begin with stage A with baseline risk factors, the patient moves to stage B as asymptomatic pre-heart failure and advances to stage C once symptomatic heart failure develops; as the heart failure stage advances, quality of life and exercise capacity decline, while prognosis becomes poor. Patients with stage C heart failure may progress to stage D advanced heart failure or transition through dynamic, non-linear states of clinical improvement, remission and, in some cases, recovery. It must be noted that death, including sudden cardiac death, can occur at any stage of the disease.

Stage A  

Patients under Stage A are those at high risk for heart failure but without structural or functional heart disease or prior or current signs or symptoms of heart failure. Abnormal cardiac biomarkers are absent in these patients. At risk are individuals with hypertension, atherosclerotic cardiovascular disease, congenital heart disease, diabetes, obesity, metabolic syndrome, thyroid disease, renal disease, familial hypercholesterolemia, or family history of or genetic variant for cardiomyopathy; cigarette smoking and the use of/exposure to cardiotoxins are also risk factors.

Stage B  

Patients under Stage B are those with structural or functional heart disease but without prior or current signs or symptoms of heart failure (pre-heart failure). This includes patients with structural abnormalities such as left ventricular hypertrophy, chamber enlargement, ventricular wall motion abnormalities, myocardial tissue abnormality, and valvular heart disease. This also includes patients with functional abnormalities such as reduced left or right ventricular systolic function, increased filling pressures on invasive hemodynamic measurements or imaging, and abnormal diastolic function. Patients have elevated levels of natriuretic peptide or high-sensitive cardiac troponin in the setting of cardiotoxin exposure. 

Stage C  

Patients under Stage C are those with structural and/or functional heart disease with prior or current signs and/or symptoms of heart failure. This includes patients with persistent heart failure or heart failure in remission. These patients also present with shortness of breath (SOB), fatigue, and decreased exercise tolerance.

Stage D  

Patients under Stage D are those with refractory, advanced, or end-stage heart failure. This includes patients with severe heart failure with persistent symptoms or signs at rest or with minimal exertion despite guideline-directed medical therapy, often requiring advanced interventions such as inotropic support, mechanical circulatory support, cardiac transplantation or palliative care.  

The following criteria for advanced heart failure must be present despite guideline-directed medical therapy and guideline-directed interventional therapy:  

• Severe and persistent heart failure symptoms (New York Heart Association [NYHA] class III or IV)
• Severe cardiac dysfunction defined by at least one of the following: 
  • Left ventricular ejection fraction ≤30%
  • Isolated right ventricular failure (eg arrhythmogenic right ventricular cardiomyopathy)
  • Non-operable severe congenital abnormalities
  • Non-operable severe valve abnormalities
  • Persistently high or increasing B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) values and severe left ventricular diastolic dysfunction or structural abnormalities
• Episodes of pulmonary or systemic congestion needing high-dose intravenous (IV) diuretics or diuretic combinations or malignant arrhythmias leading to ≥2 unplanned visits or hospitalizations in the last 12 months, or ≥1 episode of low output needing treatment with inotropes or vasoactive drugs
• Severe impairment of exercise capacity with inability to exercise, or low 6-minute walk test distance (<300 m), or peak oxygen consumption (pVO₂) <12-14 mL/kg/min, or <50% predicted value, estimated to be of cardiac origin

Assessment of Functional Capacity  

To assess the patient’s functional capacity, the NYHA Functional Classification in patients with heart failure is utilized.  

Heart Failure - Chronic_Disease Background