Heart Failure

Heart (cardiac) failure occurs when the heart can no longer meet the metabolic demands of the body at normal physiological venous pressures.  Signs of heart failure include tachycardia; venous congestion; high catecholamine levels; and, ultimately, insufficient cardiac output with poor perfusion and end-organ compromise. The causes and mechanisms of heart failure are significantly different between adults and children.

In adults, heart failure usually involves failure of the left ventricle, with the most common causes in developed nations being coronary artery disease; hypertension induced cardiac stress, arrhythmias and valvular disease. In developing nations, it has been reported that other causes are frequently implicated, including rheumatic heart disease (20.1%) and cardiomyopathy (16.8%). Many classes of disorders can result in increased cardiac demand or impaired cardiac function.  Cardiac causes include arrhythmias (tachycardia or bradycardia), structural heart disease, and myocardial dysfunction (systolic or diastolic).  Non-cardiac causes of heart failure include processes that increase the preload (volume overload), increase the afterload (hypertension), reduce the oxygen-carrying capacity of the blood (anaemia), or increase demand (sepsis).  For example, renal failure can result in heart failure due to fluid retention and anaemia.

In children, the causes of cardiac failure are significantly different from adults with many cases being due to congenital malformations, such as left to right shunts. In these patients the function of both the right and the left ventricles will be affected and these children suffer from high output cardiac failure. Other significant causes of heart failure in children are cardiomyopathy and anthracycline toxicity, which lead to low output cardiac failure. In developing nations, many cases are caused or exacerbated by anaemia, often secondary to malaria and malnutrition. It has also recently been identified that infants in ethnic minority groups in developed countries may be at risk of heart failure linked with hypocalcaemia and vitamin D deficiency.  There is also a much higher proportion of children with heart failure who have undergone cardiac procedures (61.4%) compared to adults with heart failure (0.28%); this reflects the incidence of congenital defects, frequent surgical intervention to correct this, and the subsequent and eventual deterioration in cardiac function that is seen in many of these children.

The most likely causes of heart failure depend on the age of the child.  Heart failure in the foetus, or hydrops, can be detected by performing foetal echocardiography.  In this case, heart failure may represent underlying anaemia (e.g. Rhesus sensitisation, foetal-maternal transfusion), arrhythmias or myocardial dysfunction.  Structural heart disease is rarely a cause of heart failure in the foetus, although it does occur.  Atrioventricular valve regurgitation in the foetus is a particularly troubling sign with respect to the prognosis.

Neonates and infants younger than 2 months are the most likely group to present with heart failure related to structural heart disease.  The systemic or pulmonary circulation may depend on the patency of the ductus arteriosus, especially in patients presenting in the first few days of life.

In older children, heart failure may be caused by left-sided obstructive disease (aortic stenosis or coarctation); myocardial dysfunction; hypertension; renal failure; or, more rarely, arrhythmias or myocardial ischaemia.  Illicit drugs such as inhaled cocaine and other stimulants are increasingly precipitating causes of heart failure in adolescents.  Although heart failure in adolescents can be related to structural heart disease, it is usually associated with chronic arrhythmia or acquired heart disease, such as cardiomyopathy.

Accurately estimating the incidence of heart failure in children is problematic. Congenital heart disease occurs in around 8 per 1000 live births; however, many of these children receive early surgical intervention and it has been estimated that the yearly incidence of heart failure as a result of congenital defects is between 1 and 2 per 1000 live births. As a result, cardiomyopathy contributes significantly to the number of paediatric patients who present with the symptoms of cardiac failure. Data from the United States and Australia suggests the incidence of cardiomyopathy to be 1.13 per 100,000 and 1.24 per 100,000, respectively. Nonetheless, it should be recognised that not all patients with cardiomyopathy have heart failure. This is supported by data from the UK, which reports the incidence of heart failure assessed at first presentation to hospital to be around 0.87 per 100,000. Data from Nigeria suggests that 7.02% of emergency paediatric admissions to a tertiary centre hospital are for cardiac failure, with over 90% of cases being from lower socioeconomic groups.

Uncompensated heart failure in an infant primarily manifests as a failure to thrive.  They frequently present with poor feeding, poor weight gain and chronic respiratory distress. Often, children with heart failure have diaphoresis during feedings, which is possibly related to a catecholamine surge that occurs when they are challenged with eating while in respiratory distress.  On examination, they are likely to be tachypnoeic and tachycardic and have intercostal and subcostal retractions. Cyanosis will be present in those patients with a cyanotic defect. Auscultation of the chest may reveal rales indicating pulmonary oedema. Cardiovascular examination may reveal diminished peripheral perfusion because of low cardiac output, particularly if there is an obstructive lesion such as a critical aortic stenosis or coarctation of the aorta. Auscultation of the heart may reveal a murmur compatible with the underlying diagnosis. A summation gallop may also be present and hepatomegaly is a frequent finding.

Although congenital heart defects are the predominant defect in infants, older patients are more likely to have acquired heart disease (eg rheumatic heart disease or a cardiomyopathy) or a failed repair of a congenital defect, as the cause of heart failure. In older children and adolescents the presenting symptom of heart failure are more likely to be progressive exercise intolerance, orthopnoea, dependent oedema, cool extremities, dizziness, or syncope; symptoms that are seen in adults with heart failure. A frequent complaint in adolescents, particularly those with advanced heart failure is gastrointestinal upset, with vomiting and symptoms of gastro-oesophageal reflux. On examination these patients are likely to have orthopnoea, tachypnoea and tachycardia.  They may exhibit jugular venous distension and dependent oedema is frequently seen, as is a summation gallop on auscultation. Hepatomegaly is less common in adolescents than in younger patients. 

The success of therapy of heart failure in infants and small children is judged according to the child's growth.  The failure to gain weight in the setting of marked heart failure signifies that the current regimen is not sufficient.  Continued failure to thrive is an indication for increased medical management or, when the option is available, surgical repair of structural heart disease. In general the prognosis for children with cardiomyopathy is poor, with 5 year mortality reported at around 80% and many cases progress to requiring heart transplantation when drug therapy proves insufficient.

Proveca are developing 2 drugs for the treatment of heart failure in children.