Heart Failure - Chronic Disease Background

Introduction

Heart failure is a clinical syndrome due to a structural 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, 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 1-2% 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 (HFrEF) 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 (HFpEF)  

HFpEF is characterized by impaired LV relaxation and/or filling, increased ventricular stiffness, and elevated filling pressure (LV 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 (HFrEF)  

In HFrEF, there is reduced cardiac output due to depressed myocardial contractility. HFrEF 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-blockers, 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)

Classification

Types of Heart Failure  

Heart Failure Based on Time-course  

Acute heart failure (AHF) 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 (CHF) 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 (LVEF)  

Heart failure with preserved EF (HFpEF) (diastolic heart failure) is defined as having preserved systolic function and an ejection fraction that is defined as ≥50%. The condition is not due to hypertrophic or infiltrative cardiomyopathy, high-ouput HF, or pericardial or valvular disease.  

Heart failure with reduced EF (HFrEF) (systolic heart failure) is when the patient’s ejection fraction is defined as ≤40%.  

Patients with an ejection fraction in the 41-49% range represent a ‘grey area’ and it is termed heart failure with mildly reduced ejection fraction (HFmrEF). Further criteria for the diagnosis of heart failure with preserved and mildly reduced ejection fraction include the presence of 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.  

Lastly, heart failure with improved EF (HFimpEF) is characterized by a history of HFrEF or a baseline left ventricular ejection fraction of ≤40%, whose EF has increased by ≥10% to >40%.  

Chronic Heart Failure Classification Based on Duration Since Last Admission  

This classification helps optimize guideline-directed medical therapy (GDMT) 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  

Stage A  

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

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-HF). This includes patients with previous myocardial infarction (MI), established CAD, reduced right ventricular function, left ventricular (LV) remodeling including left ventricular hypertrophy (LVH), low ejection fraction, chamber enlargement, wall motion abnormalities, asymptomatic valvular disease, arrhythmias, or congenital heart disease. In this stage, patients have elevated levels of natriuretic peptide or high-sensitive cardiac troponin in the setting of cardiotoxin exposure. There are noted increased filling pressures on invasive hemodynamic measurements or imaging.  

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. These patients have marked signs and/or symptoms at rest despite guideline-directed medical therapy, refractory or intolerant to guideline-directed medical therapy, or recurrent hospitalization. Patients under this stage require specialized treatment interventions.  

Assessment of Functional Capacity  

To assess the patient’s functional capacity, the New York Heart Association (NYHA) Functional Classification in patients with heart failure is utilized.  

Heart Failure - Chronic_Disease Background