Residency · Residency · Medicine Pediatrics
Heart Failure: From Cardiomyopathy in Children to HFrEF/HFpEF in Adults
Overview
Heart failure in children and adults differs fundamentally in etiology, classification, and treatment. Pediatric heart failure is most commonly caused by congenital heart disease and cardiomyopathy, while adult HF is predominantly ischemic and hypertensive. The Med-Peds physician must understand both the Ross classification (pediatric) and the NYHA/ACC-AHA staging (adult), as well as the limited evidence base for pediatric HF pharmacotherapy.
Etiology
Pediatric Heart Failure
Congenital heart disease: most common cause overall; left-to-right shunts (VSD, AVSD) cause volume overload HF; left-sided obstructive lesions (coarctation, critical aortic stenosis) cause pressure overload. Cardiomyopathy: Dilated cardiomyopathy (DCM): most common cardiomyopathy in children; idiopathic (66%), myocarditis, familial/genetic, neuromuscular (Duchenne), metabolic, anthracycline-related. Hypertrophic cardiomyopathy (HCM): genetic (sarcomeric mutations), Pompe disease, Noonan syndrome. Restrictive cardiomyopathy (RCM): rare in children; very poor prognosis. Left ventricular noncompaction: increasingly recognized. Myocarditis: viral (enterovirus, adenovirus, parvovirus B19); acute onset; may mimic sepsis or asthma in infants. Arrhythmias: SVT in infants causing tachycardia-induced cardiomyopathy. Kawasaki disease: coronary artery aneurysm leading to ischemic cardiomyopathy. Other: severe anemia, arteriovenous malformations, chemotherapy-related.
Adult Heart Failure
HFrEF (EF <=40%): ischemic heart disease (most common), non-ischemic DCM (idiopathic, familial, alcohol, viral, peripartum, tachycardia-mediated), valvular disease. HFpEF (EF >=50%): hypertensive heart disease, obesity, diabetes, aging, amyloidosis, HCM. HFmrEF (EF 41-49%): mildly reduced; may respond to HFrEF therapies. Right heart failure: pulmonary hypertension, RV infarct, ARVC, chronic lung disease. High-output HF: thyrotoxicosis, severe anemia, AV fistula, Paget disease, beriberi.
Classification Systems
Pediatric: Ross Classification (Modified)
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; prolonged feeding times; growth failure. Class IV: symptoms at rest; tachypnea, retractions, grunting, or diaphoresis at rest.
Adult: NYHA Functional Classification
Class I: no limitation of physical activity. Class II: slight limitation; comfortable at rest but ordinary activity causes symptoms. Class III: marked limitation; comfortable at rest but less-than-ordinary activity causes symptoms. Class IV: unable to carry on any physical activity without symptoms; symptoms at rest.
ACC/AHA Staging (Applies to Both)
Stage A: at risk (risk factors but no structural heart disease or symptoms) Stage B: structural heart disease but no symptoms. Stage C: structural heart disease with current or prior symptoms. Stage D: refractory HF requiring advanced therapies (mechanical support, transplant, palliative care)
Diagnosis
Pediatric
Clinical presentation by age: Infants: poor feeding, diaphoresis with feeds, failure to thrive, tachypnea, hepatomegaly. Older children: exercise intolerance, dyspnea, orthopnea, edema. Laboratory: BNP or NT-proBNP (age-specific reference ranges; neonatal values are physiologically elevated) Echocardiography: cornerstone of diagnosis; assess EF, chamber dimensions, valvular function, congenital anatomy. ECG: assess rhythm, chamber enlargement, ST-T changes. Cardiac MRI: gold standard for myocarditis (Lake Louise criteria), arrhythmogenic cardiomyopathy, noncompaction. Endomyocardial biopsy: selected cases (suspected myocarditis, infiltrative disease, transplant rejection)
Adult
Framingham criteria: clinical diagnosis (2 major or 1 major + 2 minor criteria) BNP/NT-proBNP: excellent negative predictive value; BNP <100 or NT-proBNP <300 makes HF unlikely. Echocardiography: EF assessment (biplane Simpson method), diastolic function grading, valvular assessment, hemodynamics. Right heart catheterization: gold standard for hemodynamic assessment; essential for transplant evaluation and differentiating HFpEF from non-cardiac dyspnea. Coronary angiography: assess for ischemic etiology. Cardiac MRI: assess viability, fibrosis (late gadolinium enhancement), infiltrative diseases.
Guideline-Directed Medical Therapy
Adult HFrEF (The Four Pillars)
| Pillar | Drug Class | Preferred Agents | Landmark Trial |
|---|---|---|---|
| 1 | ACEi/ARB/ARNI | Sacubitril-valsartan (preferred) | PARADIGM-HF |
| 2 | Beta-blocker | Carvedilol, metoprolol succinate, bisoprolol (only these 3) | MERIT-HF, COPERNICUS |
| 3 | MRA | Spironolactone, eplerenone | RALES, EMPHASIS-HF |
| 4 | SGLT2 inhibitor | Dapagliflozin, empagliflozin | DAPA-HF, EMPEROR-Reduced |
ACE inhibitor/ARB/ARNI: enalapril, lisinopril, losartan, or sacubitril-valsartan (ARNI preferred per PARADIGM-HF trial) Beta-blocker: carvedilol, metoprolol succinate, or bisoprolol (only these three have mortality benefit) Mineralocorticoid receptor antagonist (MRA): spironolactone or eplerenone (RALES, EMPHASIS-HF trials) SGLT2 inhibitor: dapagliflozin (DAPA-HF) or empagliflozin (EMPEROR-Reduced); benefit regardless of diabetes status.
Additional therapies: hydralazine + isosorbide dinitrate (especially in Black patients, A-HeFT trial), ivabradine (if HR >=70 despite beta-blocker), vericiguat (if recent HF hospitalization) Diuretics: loop diuretics for congestion (symptom relief, not mortality benefit) Devices: ICD for primary prevention if EF <=35% despite GDMT; CRT if EF <=35% + LBBB + QRS >=150ms.
Adult HFpEF
SGLT2 inhibitors: empagliflozin (EMPEROR-Preserved) and dapagliflozin (DELIVER) show benefit. Diuretics for volume management. Treat comorbidities: HTN, AF rate control, obesity management (GLP-1 agonists showing promise), sleep apnea. Spironolactone: possible benefit (TOPCAT trial, regional variation in results) No mortality benefit from ACEi, ARB, or beta-blockers in HFpEF.
Pediatric Heart Failure Pharmacotherapy
Limited evidence base: most recommendations extrapolated from adult trials. ACE inhibitors: widely used in pediatric DCM and post-CHD surgery; enalapril and captopril most common. Beta-blockers: carvedilol is most studied in children (no clear mortality benefit in pediatric trials); used for DCM and systemic RV. Digoxin: still used in pediatrics for symptomatic relief and rate control in HF with rapid AF/SVT. Diuretics: furosemide and spironolactone for volume overload. ARNI (sacubitril-valsartan): PANORAMA-HF trial in children with systemic LV dysfunction -- did not meet primary endpoint but trended toward benefit; FDA-approved for pediatric HF in 2024. SGLT2 inhibitors: pediatric trials ongoing; not yet standard in children. Milrinone: IV phosphodiesterase inhibitor; widely used in pediatric cardiac ICU for acute decompensation and post-cardiac surgery low cardiac output syndrome. Mechanical support: Berlin Heart EXCOR (pediatric VAD); bridge to transplant.
Heart Transplantation
Pediatric: ~500/year in the US; most common indications are cardiomyopathy and CHD. Adult: ~3500/year in the US; ischemic and non-ischemic DCM. Immunosuppression: calcineurin inhibitor (tacrolimus) + mycophenolate + steroids (taper) Rejection surveillance: endomyocardial biopsy, cell-free DNA (Allosure testing) Long-term complications: cardiac allograft vasculopathy, malignancy, renal insufficiency, infections.
<image>A side-by-side comparison of the four pillars of adult HFrEF guideline-directed medical therapy on the left (ACEi/ARB/ARNI, evidence-based beta-blocker, MRA, SGLT2 inhibitor, each with landmark trial names and mortality reduction percentages) and the available pediatric HF pharmacotherapy on the right (ACEi, carvedilol, digoxin, diuretics, milrinone IV), with question marks and "limited evidence" labels highlighting the gap. A connecting bridge shows ARNI and SGLT2i as emerging agents crossing from adult to pediatric practice.</image>
<image>A clinical comparison showing heart failure classification systems across ages. The Ross Classification (infant/child-specific, Classes I-IV with feeding-related symptoms) is shown alongside the NYHA Classification (adult, Classes I-IV with activity-related symptoms) and the ACC/AHA Staging system (Stages A-D, applicable across ages). Visual icons for each class show representative symptoms: an infant struggling to feed for Ross Class III, an adult unable to climb stairs for NYHA Class III, and a mechanical circulatory support device for Stage D.</image>
<image>A pie chart comparison of heart failure etiologies in pediatric versus adult populations. The pediatric pie shows congenital heart disease (largest segment), dilated cardiomyopathy, myocarditis, hypertrophic cardiomyopathy, arrhythmia-mediated, and other. The adult pie shows ischemic heart disease (largest segment), hypertensive heart disease, non-ischemic DCM, valvular disease, and other. A central annotation highlights the shift from structural/genetic causes in childhood to acquired/degenerative causes in adulthood.</image>
Clinical Pearls
In infants, heart failure often presents as poor feeding, diaphoresis with feeds, and failure to thrive -- not the classic adult symptoms of dyspnea and edema. BNP/NT-proBNP reference ranges are age-specific -- neonatal values are physiologically elevated and should not be misinterpreted as pathologic. Most pediatric HF medications are extrapolated from adult data -- the evidence base is far more limited than in adult HF. The four pillars of adult HFrEF therapy (ARNI, beta-blocker, MRA, SGLT2i) should be initiated simultaneously or in rapid succession, not in a slow stepwise fashion. Only three beta-blockers have mortality benefit in adult HFrEF: carvedilol, metoprolol succinate, and bisoprolol -- do not substitute other beta-blockers. SGLT2 inhibitors benefit both HFrEF and HFpEF regardless of diabetes status -- this is a landmark change in HF management. Milrinone is a critical IV inotrope in pediatric cardiac ICU but has no role in chronic outpatient adult HF management (increased mortality, PROMISE trial) An infant presenting with tachycardia, hepatomegaly, and respiratory distress may have SVT-induced cardiomyopathy -- always check the heart rate carefully.
References
- Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure. J Am Coll Cardiol. 2022;79(17):e263-e421.
- Kirk R, Dipchand AI, Rosenthal DN, et al. ISHLT consensus statement on pediatric heart failure. J Heart Lung Transplant. 2014;33(9):888-909.
- McMurray JJV, Packer M, Desai AS, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure (PARADIGM-HF). N Engl J Med. 2014;371(11):993-1004.
- Shaddy RE, Boucek MM, Hsu DT, et al. Carvedilol for children and adolescents with heart failure: a randomized controlled trial. JAMA. 2007;298(10):1171-1179.
- Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart failure with a preserved ejection fraction (EMPEROR-Preserved). N Engl J Med. 2021;385(16):1451-1461.
