B. Scope of the Guidelines
Grading of evidence and practice Recommendations
|Quality of evidence||Interpretation|
|High||Further research is very unlikely to change our confidence in the estimate of effect|
|Moderate||Further research is likely to have an important influence on our confidence in the estimate of effect and might change the estimate|
|Low||Further research is very likely to have an important influence on our confidence in the estimate of effect and is likely to change the estimate|
|Very low||Any estimate of effect is very uncertain|
|Strong||The desirable effects clearly outweigh the undesirable effects, or clearly do not|
|Conditional||The trade-offs are less certain, either because of low-quality evidence or because evidence suggests that desirable and undesirable effects are closely balanced|
D. Presentation and Detection of HF in Children
- 1.Possible coexistence of structural congenital heart lesions, with simultaneous pulmonary overcirculation and systemic underperfusion (when the 2 circulations are linked in parallel by an intracardiac shunt or a patent arterial duct).
- 2.A change in symptom complexes over time from infancy through adolescence. In infants and young children, these are primarily respiratory and feeding difficulties (which are similar to the metabolic demands of physical exertion seen in older children).
Symptom severity and recognition
- D1.The NYHA/Ross classification is a suitable basis for symptom stratification of patients with established chronic HF, but is not essential to establishing the diagnosis, or determining the prognosis of HF in children (Strong Recommendation, Moderate-Quality Evidence).
|Commonly encountered||Less commonly encountered|
|Infants and young children|
|Older children and adolescents|
|Class of symptoms||Symptoms noted on history|
|II||Infants: mild tachypnea or diaphoresis with feeding; no growth failure|
Older children: dyspnea on moderate exertion
|III||Infants: marked tachypnea or diaphoresis with feeding; growth failure|
Older children: dyspnea on mild or minimal exertion
|IV||Tachypnea, diaphoresis or respiratory distress at rest|
Failure to thrive and nutritional deficiency conditions
- D2.Underlying cardiac disease should be considered and excluded in younger infants with feeding difficulties and growth failure when primary gastrointestinal and other common causes have been ruled out, and in infants, toddlers, and children with chronic calorie, protein, or trace element deficiency (Strong Recommendation, Moderate-Quality Evidence).
Presentation of CMs in children
Arrhythmogenic RV CM
Myocarditis in children
- D3.A high index of suspicion for CM with acute decompensated HF is necessary in emergency and primary care settings, when evaluating infants with weakness, lethargy, abdominal pain, unexplained or disproportionate tachycardia, and tachypnea22(Strong Recommendation, Low-Quality Evidence).
- D4.In suspected muscular dystrophies, symptoms and signs of congestive HF might be concealed because of reduced physical activity. Careful evaluation of myocardial function (via serial echocardiography or magnetic resonance imaging [MRI]) beginning in midchildhood is recommended (Strong Recommendation, Moderate-Quality Evidence).
- D5.Myocarditis should always be considered in the differential diagnosis of children who present with a viral prodrome and nonspecific respiratory or abdominal symptoms associated with tachycardia, hypotension, or cardiac rhythm abnormalities, even in the absence of cardiomegaly on chest x-ray (CXR) (Strong Recommendation, Low-Quality Evidence).
Methods in practice
- •Signs and symptoms of congestive left and right HF might also occur in primary restrictive CM. These include tachypnea, dyspnea (with or without exertion), orthopnea, diaphoresis, hepatomegaly, jugular venous distension, and edema.
- •Myocarditis might present with ectopic ventricular rhythm, and limited classical symptoms of acute HF.23It might also progress to a fulminant state within a short time, characterized by the evolution of cardiac findings to those of circulatory shock within hours. Most deaths appear to occur early in the disease progression,24and the severity of presenting illness appears to affect survival.25Therefore, caution and close follow-up is required for patients who are believed to have myocarditis, and appear only mildly affected on first assessment.
- •Cardiomegaly is not usually prominent in acute myocarditis, and therefore a CXR can be misleading. It is important to have a high index of suspicion, and to include myocarditis early in the differential diagnosis of children who present with gastrointestinal (abdominal pain and vomiting) or flu-like symptoms, because the differentiation from noncardiac illnesses is difficult at symptom onset.
Evaluating the need for treatment
E. Diagnosis of HF in Children
Biochemical and routine laboratory testing
- E2.Assessment of electrolytes (Na+, K+, Cl−, Ca2+), glucose, acid-base status, urea and creatinine, hepatic transaminases, thyroid hormone levels, and a complete blood count should be performed at initial presentation of HF and repeated as needed to assess ongoing clinical status (Strong Recommendation, Low-Quality Evidence).
Electrocardiography and cardiac rhythm assessment
Ambulatory ECG/Holter monitoring
- E3.All patients should have 12-lead ECG performed at the time of presentation with HF, to exclude features of congenital or ischemic heart disease, arrhythmia and pre-excitation (Strong Recommendation, Moderate-Quality Evidence).
- E4.Holter/ambulatory ECG monitoring is not indicated as a primary diagnostic test in HF, unless HCM, arrhythmogenic RV CM, or tachycardia-induced CM is the suspected cause (Conditional Recommendation, Low-Quality Evidence).
- E5.Holter/ambulatory ECG monitoring might be indicated during chronic follow-up, particularly in higher arrhythmia risk groups, including patients with primary restrictive CM or HCM, with tachycardia-induced CM, or those who are taking anti-arrhythmic therapy (Conditional Recommendation, Low-Quality Evidence).
Patients with initial presentation of HF
- Lang R.M.
- Bierig M.
- Devereux R.B.
- et al.
Screening of patients at risk
Serial echocardiography in HF follow-up
- E6.All patients with symptoms consistent with HF should undergo transthoracic echocardiography in a pediatric cardiology facility at, or as soon as possible after, initial presentation. This initial echocardiographic study should include as a minimum (Strong Recommendation, High-Quality Evidence):
- •Ruling out congenital heart disease (with attention to coronary arteries);
- •Assessment of myocardial appearance for phenotypic patterns of CM;
- •Assessment of the systolic function parameters of the left ventricle by determining the SF and/or EF;
- •Measurement of the LV end diastolic dimension Z-score;
- •Determination of the presence of mitral regurgitation;
- •Quantitative or qualitative assessment of RV function and RV pressure;
- •Assessment of LV diastolic function;
- •Exclusion of intracardiac thrombus.
- E7.Populations at increased risk for ventricular dysfunction should undergo routine periodic screening echocardiography even in the absence of cardiac symptoms (Strong Recommendation, Moderate-Quality Evidence).
- E8.All patients with HF should undergo periodic follow-up echocardiography to reassess ventricular function with respect to response to medical therapy and to assess further progression of ventricular dysfunction. Follow-up echocardiography should also be repeated if there is a significant change in the clinical status of the patient, either in terms of improvement or deterioration (Strong Recommendation, Moderate-Quality Evidence).
Natriuretic peptide biomarkers
Metabolic and genetic testing
- E10.All pediatric patients presenting with HF require a thorough personal health history and a family history including a 3-generation pedigree (Strong Recommendation, High-Quality Evidence).
- E11.Metabolic laboratory testing in children with unexplained CM (of hypertrophic, dilated, or noncompaction phenotype) should be based on clinical presentation and assisted by specialist consultation: virtually all undiagnosed patients, whether there is a familial pattern or not, require primary screening tests, including serum amino acids, organic acids, total and free carnitine levels, lactate, and urine testing for ketones, mucopolysaccharides, and oligosaccharides (Strong Recommendation, High-Quality Evidence).
- E12.Specialty consultation with genetic and/or metabolic services is recommended to guide further testing such as muscle biopsy or specific gene screening, molecular, or cytogenetic testing. Excluding familial CM is crucial, especially when the presentation is in the fetus or newborn (Strong Recommendation, High-Quality Evidence).
- E13.At-risk family members might require secondary diagnostic screening, including genetic testing, echocardiography, or other relevant modalities of screening, depending on the etiology identified (Conditional Recommendation, Low-Quality Evidence).
Endomyocardial biopsy for acute myocarditis
- E14.A diagnosis of acute myocarditis should be considered in all children, regardless of age, who present with new onset HF without a history of decreased functional capacity, and specifically if echocardiographic ventricular dilation is less than expected for the degree of systolic dysfunction and clinical severity (Strong Recommendation, Moderate-Quality Evidence).
- E15.EMB should only be performed if confirming the clinical diagnosis of myocarditis will have a clear effect on the patient treatment plan (for example, listing for transplantation). EMB is not recommended in infants weighing less than 10 kg, or in patients who are hemodynamically unstable (Strong Recommendation, Moderate-Quality Evidence).
F. Medical Treatment of the Child With Acute HF
Acute therapy for HF
Vasopressin antagonist agents (tolvaptan, conivaptan, and others)
Methods in practice
- •The goal of therapy is to return patients to a euvolemic state, over a period of days to weeks. Subsequently, gradual weaning to the lowest required dose of diuretic is appropriate. Blood pressure, electrolyte, and renal function indices should be monitored. Fluid intake restriction to 80% of basal metabolic requirements might be necessary in some patients, depending on their caloric status and needs. A reduction of free water and an increase in calorie-rich fluid intake is desirable in most settings.
- •Patients who are unresponsive to loop diuretic agents alone might benefit from the addition of a thiazide agent. Metolazone is the most commonly used agent, but the benefit is probably a class effect. Hypokalemia or hyponatremia are commonly noted with this combination, and therefore electrolyte monitoring is important.
- F2.Children presenting with HF because of reduced cardiac output with end-organ dysfunction are likely to benefit from inotropic therapy as a rescue strategy. In this setting, milrinone, dobutamine, and low dose epinephrine have all shown efficacy in children (Strong Recommendation, Low-Quality Evidence).
- F3.Inotropic therapy should be confined to patients with depressed systolic function and clinical evidence of low cardiac output syndrome who can be closely monitored for tachyarrhythmias and blood pressure lability (Strong Recommendation, Moderate-Quality Evidence).
Chronic therapy for HF: angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker therapy
- F4.The use of ACEi therapy is indicated in children with HF because of primary heart muscle disease of the systemic left ventricle (Strong Recommendation, Moderate-Quality Evidence).
Methods in practice
- •In advanced HF, ACEi therapy introduction should occur after stabilization of HF symptoms with diuretic and simultaneous to inotropic support withdrawal. Uptitration can proceed safely over 3-10 days in most inpatients, and can be more gradual in outpatients.
- •Captopril is the typical first choice for most infants and with enalapril being an appropriate choice for those older than the age of 2 years (see Supplemental Table 2). The use of a captopril tablet dissolved in a precise volume of water, and dosing a fraction of the suspension (dissolve and dose method) overcomes the problem of the short half-life of this medication in suspension form.
- •In older children with stable hemodynamic status, longer-acting ACEi therapy, such as ramipril and perindopril, might be considered for use to enhance adherence.
- •Caution is advised when these agents are used in the first 4 months of life, because renal dysfunction is more common,116and therefore uptitration must be carefully monitored. A small drop in systolic blood pressure is typically noted in patients who take an ACEi. This might occasionally exceed the expected 5%-10% drop in baseline values, necessitating observation for up to 2 hours after the first dose.117The magnitude of the effect has been reported to be greater in patients with high renin levels (who commonly also have hyponatremia).106,118
- •A creatinine rise of greater than 50% over baseline value in any patient requires a reassessment of fluid balance and diuretic therapy, and consideration for a dosage reduction or withdrawal of ACEi therapy.116
- •Adequate pregnancy avoidance measures are required in adolescent female patients who take an ACEi because of its teratogenic effects.
- F5.Treatment with a β-adrenergic antagonist such as carvedilol, metoprolol, or bisoprolol might be initiated in the treatment of moderate to severe systolic dysfunction of a systemic left ventricle (Conditional Recommendation, Moderate-Quality Evidence).
Methods in practice
- •Dosing and uptitration instructions are provided in Supplemental Table S2. In general, a starting dose of 0.05 mg/kg every 12 hours is required, with pharmacokinetics in children younger than 4 years favouring dosing every 8 hours.
- •The initiation of β-blocker therapy after inotropic support requires caution. There is limited evidence to guide practice, so Recommendations for decision-making are largely empirical, with a guide provided in Figure 2. It should be noted that initiation of β-blocker therapy might be considered in children who are asymptomatic but have a persistent moderate reduction in LV EF (usually less than 40%) despite being established while using optimal ACEi therapy, especially if the etiology is considered to be ischemic heart disease. The general approach to sequential addition of chronic medical therapy in pediatric HF patients is summarized in Figure 3.
- •In older children with stable hemodynamic status, consideration might be given to starting a β-blocker as soon as ACEi dosing has been established.
Aldosterone antagonist therapy
- F6.Aldosterone antagonist therapy is reasonable in children with chronic systolic HF, provided renal function is normal or only mildly impaired. Close monitoring of renal function and serum potassium is required when coadministering aldosterone antagonist therapy with ACEi therapy (Conditional Recommendation, Low-Quality Evidence).
Methods in practice
- •Spironolactone is the typical agent used, because experience with eplerenone in children is limited. Spironolactone is typically initiated for patients in whom therapy with an ACEi and β-blocker has not resulted in improved ventricular function or reversal of ventricular remodelling (as indicated in Fig. 3).
- •Hyperkalemia might result in patients who receive spironolactone and an ACEi, especially if renal function is already compromised. Therefore, potassium levels and renal function indices should be checked before starting spironolactone, within 7-14 days after introduction, and periodically thereafter. Any potassium supplementation should be carefully re-evaluated.
- •Male gynaecomastia is a nonreversible complication, and must be closely monitored.
Medical management of myocarditis
Intravenous immunoglobulin G
- F7.A standard approach to HF management should be applied in patients with myocarditis including inotropic support and diuretic therapy (Strong Recommendation, Moderate-Quality Evidence).
- F8.For fulminant myocarditis, mechanical circulatory support should be considered. Invasive therapies are considered acceptable considering the prospect of spontaneous recovery (Strong Recommendation, Moderate-Quality Evidence).
- F9.Corticosteroids are not recommended as a routine treatment for myocarditis, particularly in the absence of robust randomized controlled trial evidence. Continued speculative use of immunosuppressive therapy in the absence of a prospective clinical trial will not contribute to the evidence base of management for this disorder (Conditional Recommendation, Low-Quality Evidence).
- F10.IVIG is not recommended as a routine treatment for myocarditis (Conditional Recommendation, Low-Quality Evidence).
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This statement was developed following a thorough consideration of medical literature and the best available evidence and clinical experience. It represents the consensus of a Canadian panel comprised of multidisciplinary experts on this topic with a mandate to formulate disease-specific Recommendations. These Recommendations are aimed to provide a reasonable and practical approach to care for specialists and allied health professionals obliged with the duty of bestowing optimal care to patients and families, and can be subject to change as scientific knowledge and technology advance and as practice patterns evolve. The statement is not intended to be a substitute for physicians using their individual judgement in managing clinical care in consultation with the patient, with appropriate regard to all the individual circumstances of the patient, diagnostic and treatment options available and available resources. Adherence to these Recommendations will not necessarily produce successful outcomes in every case.