Heart Failure

Definition

Heart failure is described as a syndrome of inadequate cardiac output to maintain end organ perfusion. It could be due systolic or diastolic dysfunction. Patients with left to right shunts develop congestive heart failure (CHF) because of excessive volume overload to the lungs with a normal cardiac function.

Compensatory Mechanisms

Catecholamine surge by the sympathetic nervous system that leads to tachycardia and increased myocardial contractility to increase the cardiac output.

Salt and water retention through activation of the renin-angiotensin-aldosterone system (RAAS) to increase the intravascular volume and enhance the end organ perfusion.

Table showing two classification systems of heart failure in children and adults
Ross Classification of Heart Failure in Children
Class I	Asymptomatic
Class II	Mild tachypnea or diaphoresis with feeding in infants, dyspnea on exertion in older children
Class III	Marked tachypnea or diaphoresis with feeding in infants, marked dyspnea on exertion in older children
Class IV	Symptoms such as tachypnea, retractions, grunting or diaphoresis at rest

NYHA Classification of Heart Failure in Adults
Class I	Symptoms are only present at exertion that would limit normal individuals
Class II	Symptoms are present at ordinary levels of exertion
Class III	Symptoms are present at less than ordinary levels of exertion
Class IV	Symptoms at rest

Etiology

Table showing mechanisms of heart failure in neonates/infants
Underlying mechanism	Examples
Pressure overload	Critical aortic stenosis (AS), Coarctation of aorta/interrupted aortic arch
Volume overload	Left to right shunts such as VSD, AVSD, PDA, truncus arteriosus, aortic pulmonary (AP) window
Valvular dysfunction	AV valve insufficiency after AVSD repair, semilunar valve insufficiency, truncal valve regurgitation, TOF with absent pulmonary valve
Myocardial dysfunction	Ischemia, anomalous left coronary artery from the pulmonary artery (ALCAPA)
Cardiomyopathy	Primary and secondary myocarditis
Post-op ventricular dysfunction

Table showing etiologies of heart failure in children/adolescents
Underlying mechanism	Examples
Left heart failure	MR, AR, progressive AS
Right heart failure	Ebstein's anomaly, Eisenmenger syndrome
Cardiomyopathy (primary)	Dilated, hypertrophic, restrictive
Cardiomyopathy (secondary)	Myocarditis
Chronic arrhythmia	SVT
Toxins	Anthracyclines, radiation
Metabolic disorders	Glycogen storage diseases

Clinical features

Diagnosis

CBC (may show anemia) and thrombocytosis in case of Kawasaki disease
CMP (look for elevated LFT's and BUN/Cr, may have elevated Na and low K secondary to activation of RAAS)
Troponin I (only useful if concerned about acute ischemic injury)
CK-MB (non-specific marker of cardiac injury)
BNP/NTproBNP (see discussion below)
Lactate (if concerned about low cardiac output)

CXR (cardiomegaly, pulmonary edema)
Echocardiogram (evaluate cardiac structure/function and coronary arteries)
Cardiac MRI (done in cases of myocarditis/cardiomyopathies for risk stratification)

The ideal biomarker would have the following properties:

Specific for the myocardium
Is released in quantities sufficient to be detected by an assay with sufficient sensitivity and specificity to distinguish between healthy and disease states
A relationship can be determined between the serum level of the biomarker and the clinical severity of the disease state
Can provide diagnostic and prognostic information

The prototype biomarker is Brain Natriuretic Peptide (BNP)
BNP and its inactive processed product, N-terminal-pro-BNP (NTproBNP), are released from ventricular myocardium in response to increased myocardial fiber stretch
BNP and NTproBNP have different biochemical properties, are measured by different assays
NTproBNP has a longer half-life in plasma than BNP; therefore, NTproBNP levels are generally higher than BNP and display less variability

Management of CHF

1. Diuretics:

Reduce symptoms of volume overload such as dyspnea, orthopnea, peripheral edema, hepatomegaly
Loop diuretics (furosemide, bumetanide) are typically used as first-line agents, with thiazide diuretics (chlorothiazide, metolazone) added for refractory fluid retention
Frequent monitoring of serum electrolytes is necessary, particularly if diuretics are used in combination with ACE inhibitors and/or digoxin

Table showing the commonly used diuretics in pediatric CHF
Drug	Class	Action
Furosemide	Loop diuretic	Inhibits Na/K/Cl transport in ascending loop of Henle
Bumetanide	Loop diuretic	Inhibits Na/K/Cl transport in ascending loop of Henle
Hydrochlorothiazide	Thiazide	Inhibits Na/Cl transport in distal tubule
Metolazone	Thiazide	Inhibits Na/Cl transport in distal tubule

2. ACE inhibitors/Angiotensin Receptor Blockers (ARBs):

Afterload reduction of the left ventricle through systemic vasodilation has been a basic therapeutic premise of heart failure
ACE inhibitors effect systemic vasodilation through blockade of ACE which converts angiotensin I into angiotensin II
ARBs produce similar effects by blocking the angiotensin receptors

3. Beta-Blockers:

Beta-blockers are widely used in chronic heart failure
Beta-blockers improve left ventricular function, heart failure symptoms, and survival in adults
Potential mechanisms of include up regulation of beta-adrenergic receptors, decreased stimulation of other neuro-hormonal systems, antiarrhythmic effects, coronary vasodilation, negative chronotropic effects, antioxidant effects, and improved myocardial energetics

4. Aldosterone receptor antagonists:

The aldosterone receptor antagonists such as spironolactone prevent aldosterone from exerting adverse compensatory downstream mechanisms that are activated in chronic heart failure, many of which involve sodium and extracellular fluid retention
Evidence also indicates that chronic aldosterone receptor stimulation leads to adverse remodeling such as myocardial scarring/fibrosis, ventricular dilation, and ventricular dysfunction
Spironolactone is generally well tolerated in children, although hyperkalemia is a common side effect necessitating careful monitoring of serum electrolytes
Gynecomastia can occur in males (up to 10%) and may be irreversible

5. Digoxin:

Digoxin is a cardiac glycoside, which exerts positive inotropic effects on the heart by increasing sarcoplasmic calcium concentrations by inhibition of the sodium-potassium ATPase pump of the myocardial cellular membrane
Digoxin also counteracts the adverse neuro-hormonal milieu of chronic heart failure by increasing vagal tone and sympatholytic effects, decreasing plasma norepinephrine levels, and possibly antagonism of aldosterone
Digoxin is currently indicated for chronic heart failure in adults for patients who remain symptomatic despite adherence to guideline-directed medical therapy

6. Inotropes:

Inotropes are frequently used in the inpatient setting to improve ventricular function or augment cardiac output in patients with exacerbations of chronic heart failure
At present, there are no oral agents with inotropic properties, apart from digoxin, available in the United States
In some situations, continuous inotropic therapy may be used as part of a palliative care strategy or as a bridge to more definitive treatment such as ventricular assist device or heart transplantation

7. Interventional catheterization:

These procedures may be used for myocardial biopsy and to evaluate the cardiac hemodynamics
Interventional balloon valvuloplasty may be needed for critical aortic or pulmonary stenosis

8. Surgery:

It is often the definitive treatment of heart failure if it is secondary to structural heart diseases

Pediatric Cardiology Part 1