DESCRIPTION

• Heart failure (HF) is a clinical syndrome in which the heart is unable to deliver sufficient blood to meet the metabolic demands of the body.
• Results from ventricular dysfunction and/or volume or pressure overload alone or in combination
• The cardiac causes of pediatric HF can be broadly classified into congenital heart disease (CHD), cardiomyopathy (CM), acquired heart disease, and primary arrhythmia.

EPIDEMIOLOGY

• The estimated incidence of acute decompensated HF (ADHF) in the pediatric population is approximately 0.9 to 7.4 per 100,000 children.
• Prevalence of chronic HF is more difficult to determine.
• ADHF carries a high burden of morbidity and mortality.
  • Overall, 7–20% of ADHF-related hospitalizations result in death.

ETIOLOGY

The most common cardiac causes of HF in pediatric patients include the following:

• CHD
• CM
• Acquired conditions

RISK FACTORS

• Congenital heart defects
  • Most common cause of ADHF, up to 60% of HF hospitalizations
  • Volume overload lesions include the following:
    • Left-to-right shunting lesions: atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA), atrioventricular septal defects (AVSD)
    • Partial anomalous pulmonary venous connections (PAPVR)
  • Pressure overload lesions include the following:
    • Right ventricular (RV) pressure load—severe pulmonary stenosis, premature closure of ductus arteriosus with pulmonary hypertension (PHTN) and isolated RV failure
    • Left ventricular (LV) pressure load—aortic stenosis (AS), coarctation of the aorta
  • Single-ventricle population is the largest proportion of CHD patients who develop HF.
  • Congenital coronary anomalies—anomalous left coronary artery from pulmonary artery (ALCAPA)
• CM
  • The annual incidence of CM is ~1.1 to 1.2 per 100,000 children, with a peak incidence occurring in infancy 7.8 to 8.3 per 100,000 per year.
  • CM can be divided into the following:
    • Dilated CM (DCM) about 50%
    • Hypertrophic CM (HCM) about 40% (obstructive or nonobstructive)
    • Restrictive CM (RCM) up to 5%
    • LV noncompaction CM up to 5% can occur in isolation or overlapping with DCM or HCM.
    • RV CMs <1% such as arrhythmogenic RV CM and Uhl anomaly
  • For about 2/3 of primary CMs, a genetic cause can be identified; higher odds for HCM than DCM
• Acquired heart disease
  • Most causes of acquired heart disease are modifiable.
    • Autoimmune causes—systemic lupus erythematosus (SLE)
    • Infectious/inflammatory causes—pericarditis, myocarditis, endocarditis, acute rheumatic fever, Kawasaki disease, multisystem inflammatory syndrome in children (MIS-C)
    • Renal causes—renal disease (volume overload), severe hypertension
    • Endocrine causes—hyperthyroidism, maternal diabetes
    • Metabolic causes—Pompe disease, Noonan syndrome (Ras-opathies)
    • Genetic/neuromuscular causes—mitochondrial diseases, Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy
    • Hematologic—anemia, twin-twin transfusion
    • Oncologic—cancer therapies (cardiotoxic chemotherapy)
    • Cor pulmonale (primary PHTN, Eisenmenger syndrome, chronic lung disease)
  • Risk factors for the development of acquired heart disease are disease specific.
• Arrhythmia
  • Primary arrhythmias: supraventricular or ventricular tachycardia, complete heart block (CHB)
  • Repaired heart defects

GENERAL PREVENTION

• Counseling for a heart-healthy lifestyle (exercise, nutrition, weight management, normotension)
• Prompt identification and treatment of both CHD and any underlying autoimmune, infectious/inflammatory, endocrine, and renal disorders to prevent the development of ADHF as an associated complication
• Limited use of anthracycline drugs in cancer therapy
• Early angiotensin-converting enzyme (ACE) inhibitors may slow the progression of LV systolic dysfunction in muscular dystrophy.
• Appropriate endocarditis prophylaxis

PATHOPHYSIOLOGY

• Regardless of the underlying etiology, inadequate supply/cardiac output (CO) to meet the body’s metabolic demand results in two major compensatory mechanisms.
  • Activation of the sympathetic nervous system:
    • Reduced CO results in reduced stimulation of the baroreceptors which leads to the activation of the sympathetic nervous system with increased release and decreased uptake of norepinephrine causing peripheral vasoconstriction with an increase in systemic vascular resistance (SVR) which allows for maintenance of mean arterial pressure (MAP) and organ perfusion.
  • Activation of the renin-angiotensin-aldosterone system (RAAS):
    • Reduced CO results in decreased renal perfusion which leads to the activation of the RAAS with increased production and circulating levels of renin, angiotensin II, and aldosterone.
    • Renin is responsible of cleaving angiotensinogen into angiotensin I, which is converted into angiotensin II by the ACE
    • Angiotensin II is a potent vasoconstrictor that preserves end-organ perfusion.
    • Aldosterone causes salt and water retention, resulting in increased preload and then CO according to the Frank-Starling mechanism.
• These compensatory mechanisms are temporizing. Over time, they are maladaptive to the patient:
  • Increased levels of catecholamines will ultimately lead to further cardiomyocyte injury, dysfunctional intracellular signaling, and ultimately cardiomyocyte death.
  • Long-term elevation of aldosterone and angiotensin II promotes cardiac fibrosis and apoptosis.
• The main theory behind chronic medical management of CHF using β-adrenergic blockers and ACE inhibitors is to block the maladaptive role of these two systems.