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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

The International Society for Heart and Lung Transplantation Guidelines for the management of pediatric heart failure: Executive summary

      These guidelines have been produced to bring together current recommendations on the evaluation and management of pediatric heart failure (HF) and update the previous guideline.
      • Rosenthal D.
      • Chrisant M.R.K.
      • Edens E.
      • et al.
      International Society for Heart and Lung Transplantation: practice guidelines for management of heart failure in children.
      The writing group was chosen from the membership of the International Society for Heart and Lung Transplantation (ISHLT), the Association of European Pediatric and Congenital Cardiology (AEPC), and the Pediatric and Congenital Electrophysiology Society (PACES) across health care disciplines to achieve representation of HF practice throughout the world. Overall, 90 contributors from 13 counties across 4 continents (Appendix 1) were assigned various aspects of HF according to their expertise. A comprehensive review of the available published evidence for HF management was undertaken. The strength and level of evidence was assessed according to standard practice.
      U. S. Task Force Staff
      Guide to Clinical Preventive Services: report of the U.S. Preventive Services Task Force.
      The recommendations were achieved by consensus with the contributors; however, it is recognized that the evidence base for many of the recommendations is Level C due to the lack of trials in children. In some areas, there is such a lack of information that no recommendations can be made: it is hoped that by recognizing these deficiencies, research will be stimulated to address them. External review was undertaken by 8 international experts invited from adult advanced HF, pediatric cardiology, and congenital cardiovascular surgery (Appendix 2). The final guidelines were reviewed and approved by the ISHLT Board and Standards & Guidelines Committee, endorsed by the AEPC, and those guidelines pertinent to electrophysiology, by the PACES Executive Committee.
      The background information for these guidelines and complete references have been published in the monograph series, Volume 8 by the ISHLT.
      The abbreviations used are listed in Appendix 3.

      Definition and documentation recommendation
      • Hsu D.T.
      • Pearson G.D.
      Heart failure in children: part I: history, etiology, and pathophysiology.
      • Ross R.D.
      The Ross classification for heart failure in children after 25 years: a review and an age-stratified revision.

      Chairs: Richard Kirk, Anne I. Dipchand, and David N. Rosenthal
      HF in children is a clinical and pathophysiologic syndrome that results from ventricular dysfunction, volume, or pressure overload, alone or in combination. It leads to characteristic signs and symptoms, such as poor growth, feeding difficulties, respiratory distress, exercise intolerance, and fatigue, and is associated with circulatory, neurohormonal, and molecular abnormalities. HF has numerous etiologies that are a consequence of cardiac and non-cardiac disorders, either congenital or acquired.
      Class I
      • 1.
        The documentation of HF severity and when appropriate, staging facilitates monitoring of disease progression and patient management (Table 1): Level of Evidence C
        Table 1Heart Failure Severity Classifications
        ClassNYHARoss
        INo limitations of physical activityNo limitations or symptoms
        IIMay experience fatigue, palpitations, dyspnea, or angina during moderate exercise but not during restMild tachypnea or diaphoresis with feeding
        IIISymptoms with minimal exertion that interfere with normal daily activityInfants with growth failure and marked tachypnea or diaphoresis with feedings, older children with marked dyspnea on exertion
        IVUnable to carry out any physical activity because they typically have symptoms of HF at rest that worsens with any exertionSymptoms at rest such as tachypnea, retractions, grunting, or diaphoresis
        Expansions for the abbreviations used in Table 1 are provided in Appendix 3.

      Genetic testing recommendations

      Chairs: Richard Kirk and Jeffery Towbin

      Dilated cardiomyopathy
      • Ferlini A.
      • Neri M.
      • Gualandi F.
      The medical genetics of dystrophinopathies: molecular genetic diagnosis and its impact on clinical practice.
      • Bowles N.E.
      • Bowles K.R.
      • Towbin J.A.
      The “final common pathway” hypothesis and inherited cardiovascular disease. The role of cytoskeletal proteins in dilated cardiomyopathy.
      • Baig M.K.
      • Goldman J.H.
      • Caforio A.L.
      • Coonar A.S.
      • Keeling P.J.
      • McKenna W.J.
      Familial dilated cardiomyopathy: cardiac abnormalities are common in asymptomatic relatives and may represent early disease.
      • Ackerman M.J.
      • Priori S.G.
      • Willems S.
      • et al.
      HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA).
      • Mestroni L.
      • Taylor M.R.G.
      Genetics and genetic testing of dilated cardiomyopathy: a new perspective.

      Class I
      • 1.
        Comprehensive or targeted DCM genetic testing (LMNA and SCN5) is recommended for patients with DCM and significant cardiac conduction disease (i.e., first-, second-, or third-degree heart block) and/or a family history of premature unexpected sudden death. Level of Evidence C
      • 2.
        Mutation-specific genetic testing is recommended for first-degree family members after the identification of a DCM-causative mutation in the index case. Level of Evidence C
      Class IIa
      • 1.
        Genetic testing can be useful for patients with familial DCM to confirm the diagnosis, to recognize those who are at highest risk of arrhythmia and syndromic features, to facilitate cascade screening within the family, and to help with family planning. Level of Evidence C

      Hypertrophic cardiomyopathy
      • Ackerman M.J.
      • Priori S.G.
      • Willems S.
      • et al.
      HRS/EHRA expert consensus statement on the state of genetic testing for the channelopathies and cardiomyopathies this document was developed as a partnership between the Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA).
      • Thierfelder L.
      • Watkins H.
      • MacRae C.
      • et al.
      Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere.
      • Teekakirikul P.
      • Kelly M.A.
      • Rehm H.L.
      • Lakdawala N.K.
      • Funke B.H.
      Inherited cardiomyopathies: molecular genetics and clinical genetic testing in the postgenomic era.
      • Kindel S.J.
      • Miller E.M.
      • Gupta R.
      • et al.
      Pediatric cardiomyopathy: importance of genetic and metabolic evaluation.

      Class IIa
      • 1.
        Genetic testing is indicated in the most clinically affected individual to facilitate screening. Level of Evidence A
      • 2.
        Mutation-specific genetic testing is recommended for first-degree family members after the identification of an HCM-causative mutation in the index case. Level of Evidence A

      Restrictive cardiomyopathy
      • Caleshu C.
      • Sakhuja R.
      • Nussbaum R.L.
      • et al.
      Furthering the link between the sarcomere and primary cardiomyopathies: restrictive cardiomyopathy associated with multiple mutations in genes previously associated with hypertrophic or dilated cardiomyopathy.
      • Sen-Chowdhry S.
      • Syrris P.
      • McKenna W.J.
      Genetics of restrictive cardiomyopathy.

      Class I
      • 1.
        Mutation-specific genetic testing is recommended for first-degree family members after the identification of an RCM-causative mutation in the index case. Level of Evidence C
      Class IIb
      • 1.
        RCM genetic testing may be considered for patients in whom a cardiologist has established a clinical index of suspicion for RCM based on examination of the patient’s clinical history, family history, and ECG/echocardiographic phenotype. Level of Evidence C

      LV non-compaction cardiomyopathy
      • Tang S.
      • Batra A.
      • Zhang Y.
      • Ebenroth E.S.
      • Huang T.
      Left ventricular noncompaction is associated with mutations in the mitochondrial genome.

      Class I
      • 1.
        Mutation-specific genetic testing is recommended for first-degree family members after the identification of an LVNC-causative mutation in the index case. Level of Evidence C
      Class IIa
      • 1.
        LVNC genetic testing can be useful for patients in whom a cardiologist has established a clinical diagnosis of LVNC based on an examination of the patient’s clinical history, family history, and ECG/echocardiographic phenotype. Level of Evidence C

      Arrhythmogenic ventricular cardiomyopathy
      • Marcus F.I.
      • McKenna W.J.
      • Sherrill D.
      • et al.
      Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the Task Force Criteria.
      • Vatta M.
      • Marcus F.
      • Towbin J.A.
      Arrhythmogenic right ventricular cardiomyopathy: a “final common pathway” that defines clinical phenotype.

      Class I
      • 1.
        Mutation-specific genetic testing is recommended for first-degree family members after the identification of the AVC-causative mutation in an index case. Level of Evidence C
      Class IIa
      • 1.
        Comprehensive or targeted AVC genetic testing (DSC2, DSG2, DSP, JUP, PKP2, and TMEM43) can be useful for patients who satisfy task force diagnostic criteria for AVC. Level of Evidence C

      Diagnostic recommendations

      Chairs: Anne I. Dipchand, Michael Burch, and Luc Mertens

      B-Type natriuretic peptide
      • Cantinotti M.
      • Giovannini S.
      • Murzi B.
      • Clerico A.
      Diagnostic, prognostic and therapeutic relevance of B-type natriuretic hormone and related peptides in children with congenital heart diseases.
      • Price J.F.
      • Thomas A.K.
      • Grenier M.
      • et al.
      B-type natriuretic peptide predicts adverse cardiovascular events in pediatric outpatients with chronic left left ventricular systolic dysfunction.
      • Knirsch W.
      • Häusermann E.
      • Fasnacht M.
      • Hersberger M.
      • Gessler P.
      • Bauersfeld U.
      Plasma B-type natriuretic peptide levels in children with heart disease.
      • Law Y.M.
      • Hoyer A.W.
      • Reller M.D.
      • Silberbach M.
      Accuracy of plasma B-type natriuretic peptide to diagnose significant cardiovascular disease in children: the Better Not Pout Children! Study.
      • Auerbach S.R.
      • Richmond M.E.
      • Lamour J.M.
      • et al.
      BNP levels predict outcome in pediatric heart failure patients: post hoc analysis of the Pediatric Carvedilol Trial.

      Class IIb
      • 1.
        BNP/NT-proBNP can be used as an adjunctive marker in the integrated evaluation and monitoring of patients with known HF to further define severity, response to therapy, and its progression. Level of Evidence B
      • 2.
        BNP/NT-proBNP can be used as an adjunctive marker, not a stand-alone test, to aid in the diagnosis of new HF in symptomatic patients. Level of Evidence B

      Imaging
      • Lopez L.
      • Colan S.D.
      • Frommelt P.C.
      • et al.
      Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council.
      • Schiller N.B.
      • Shah P.M.
      • Crawford M.
      • et al.
      Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms.
      • Friedberg M.K.
      • Mertens L.
      Echocardiographic assessment of ventricular synchrony in congenital and acquired heart disease in children.
      • Petko C.
      • Minich L.L.
      • Everitt M.D.
      • Holubkov R.
      • Shaddy R.E.
      • Tani L.Y.
      Echocardiographic evaluation of children with systemic ventricular dysfunction treated with carvedilol.
      • Colan S.D.
      • Shirali G.
      • Margossian R.
      • et al.
      The ventricular volume variability study of the Pediatric Heart Network: study design and impact of beat averaging and variable type on the reproducibility of echocardiographic measurements in children with chronic dilated cardiomyopathy.
      • Mor-Avi V.
      • Lang R.M.
      • Badano L.P.
      • et al.
      Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography.
      • Friedberg M.K.
      • Mertens L.
      Tissue velocities, strain, and strain rate for echocardiographic assessment of ventricular function in congenital heart disease.

      Table 2 compares the imaging modalities.
      Table 2Comparison of Imaging Modalities
      ModalityAdvantagesLimitationsUse in pediatric HF
      EchocardiographyFirst-line technique for all patients in acute/chronic HF; anatomic + functional assessment possibleLimited by acoustic windowsFirst-line technique in the assessment of HF
      M-modeHigh temporal resolutionOnly works if global remodeling/dysfunctionSerial measurement of LV dimensions, wall thickness, and fractional shortening
      Normal pediatric values availableNot valid if paradoxical septal motion
      2-D echocardiographyAssessment of 2-D anatomy, identification of structural diseaseDependent on acoustic windowsIdentification of structural disease as cause for HF
      2-D EFGood parameter for global performanceGeometrical assumptionsRecommended technique for assessment of LV performance
      Can be calculated in patients with regional dysfunctionLoad dependency
      3-D EFNo geometric assumptionsHighly dependent on acoustic windowsEmergent technique replacing 2-D EF
      Lower temporal resolution
      Blood Doppler techniques (MPI, dP/dt, S/D ratio)Geometry-independentVariability of measuring time intervalsLimited use in heart failure patients
      High temporal resolutionNo spatial information
      Load dependency of different indices
      TDIGeometry-independentAngle-dependentAssessment of longitudinal function, early detection of dysfunction, assessment of diastolic function
      High temporal resolutionLimited information on its use in childrenDyssynchrony detection
      Quantification of regional functionLoad dependency
      Strain imagingGeometry-independentSoftware dependency and differences between vendorsEmergent technique
      Images myocardial mechanicsLoad dependencyDyssynchrony assessment
      Limited normal data
      Cardiac MRINot limited by imaging windows, no radiation, good for imaging extracardiac structures, flow quantification, tissue characterization (fibrosis imaging)Accessibility, requirement for general anesthesia, cost, not compatible with many devices (pacemaker, assist devices)Limited use in HF patients; quantification of RV function, patients with limited acoustic windows, fibrosis detection
      Steady-state free precession imagingClinical reference technique for quantification of LV and RV volumes + massLower temporal resolution (ECG-gated)Mainly calculation of volumes and EF
      Phase contrastReference technique for quantifying flowsLower temporal resolution than Doppler techniquesCalculation of CO, quantification of valve regurgitation
      MR taggingAllows quantifying myocardial mechanicsDifficult post-processing; lower frames rates compared with echocardiographyLimited clinical use in heart failure patients. Research tool
      Late gadolinium enhancementIdentification of regional fibrosisLimited spatial resolution, only detects regional fibrosisClinical use still uncertain; possible prognostic value in HCM, detection of EFE in DCM or obstructive lesions
      AngiographyDetection of extracardiac abnormalitiesSpatial resolution is less good than cardiac CT (coronary imaging)Can be used to detect extracardiac abnormalities causing heart failure (arch, coronary anomalies)
      Cardiac CTNot limited by imaging windows; high resolution, allows studying spatial relationships between cardiovascular structures and the airway, anesthesia often not requiredExposure to radiation, limited functional information, no flow quantification, coronary imaging influenced by high heart ratesMainly used for coronary artery imaging if uncertain about coronary artery origins on echocardiography; limited role in follow-up
      Expansions for the abbreviations used in Table 2 are provided in Appendix 3.

      Echocardiogram

      Class I
      • 1.
        Measurement of LV dimensions and LV wall thickness is an essential part of every echocardiographic functional LV assessment in patients with HF. The recent American Society of Echocardiography pediatric recommendations propose the use 2-D imaging instead of M-mode, but this was not based on actual data proving its clinical superiority. Normal values are more readily available for M-mode measurements. Level of Evidence B
      • 2.
        LV remodeling should be monitored during serial follow-up. This consists of measuring cavity dimensions, wall thickness, and where clinically relevant, LV mass. Level of Evidence B
      • 3.
        For patients with HF, assessing LV function by calculating LVEF based on a well-standardized 2-D method (biplane Simpson’s or area-length method) should be undertaken. Level of Evidence B
      Class IIa
      • 1.
        Fractional shortening can be used for sequential assessment of LV function, although caution is required in patients with abnormal or paradoxical septal motion. Level of Evidence C
      • 2.
        No recommendations can be made about the use of automated 2-D methods or 3-D echocardiography. These are emerging techniques for EF calculation that still need further validation in pediatric HF. Level of Evidence C
      Class IIb
      • 1.
        LVEF is load-dependent. The use of methods correcting for afterload have been proposed that do not improve diagnostic accuracy and predictive value. Level of Evidence C
      • 2.
        Although measured and reported, the value of blood pool Doppler parameters, such as dP/dt, myocardial performance index, and the ratio of systolic-to-diastolic duration, in the assessment of LV systolic function in pediatric patients with HF is probably limited. (Problems with reliability of measuring time intervals, loading, and heart rate dependency of the methods, and their uncertain prognostic value, all limit their clinical use.) Level of Evidence C
      • 3.
        Although measured and reported, the role of tissue Doppler imaging (TDI) and strain imaging in pediatric patients with HF is still uncertain. Pulsed TDI at the annulus has the benefit of published normal ranges and may assist in the early detection of myocardial dysfunction. Apart from the potential additional predictive information, its use in the description of mechanical dyssynchrony and identification of candidates for CRT seems to be important but requires further investigation. Level of Evidence C

      Echo diastolic function
      • Dragulescu A.
      • Mertens L.
      • Friedberg M.K.
      Interpretation of left ventricular diastolic dysfunction in children with cardiomyopathy by echocardiography: problems and limitations.

      Class IIa
      • 1.
        Diastolic function, including mitral inflow patterns, mitral annular TDI, and pulmonary venous Doppler flow patterns should be assessed by echocardiography in children with HF. The tracings should be interpreted to define the type of diastolic abnormality (relaxation abnormality, reduced compliance, restrictive filling) as well as to attempt to diagnose the presence of elevated filling pressure (Table 3 summarizes typical changes in progressive LV diastolic dysfunction). Level of Evidence C
        Table 3Summary of Typical Changes in Progressive Left Ventricular Diastolic Dysfunction
        VariableEarly relaxation abnormalityProgressive decreasing complianceRestrictive filling
        Mitral e′Persistent ↓↓↓
        Mitral E velocity
        Mitral A velocity
        Mitral E/A ratioPseudonormalizes
        Deceleration timeProgressive ↓↓↓
        Pulmonary vein D
        Pulmonary vein S↓↓
        OtherAbnormal pulmonary vein S/D ratio; increased pulmonary vein A wave reversalProminent A reversal in pulmonary veins
        D, diastole; S, systole. Expansions for the other abbreviations used in Table 3 are provided in Appendix 3.

      Cardiac MRI
      • Sarikouch S.
      • Peters B.
      • Gutberlet M.
      • et al.
      Sex-specific pediatric percentiles for ventricular size and mass as reference values for cardiac MRI: assessment by steady-state free-precession and phase-contrast MRI flow.
      • Buechel E.V.
      • Kaiser T.
      • Jackson C.
      • Schmitz A.
      • Kellenberger C.J.
      Normal right- and left ventricular volumes and myocardial mass in children measured by steady state free precession cardiovascular magnetic resonance.
      • Tham E.B.
      • Hung R.W.
      • Myers K.A.
      • Crawley C.
      • Noga M.L.
      Optimization of myocardial nulling in pediatric cardiac MRI.

      Class IIb
      • 1.
        Cardiac MRI can be used to assess LV function in children. Use can be limited due to the requirement for general anesthesia in younger children, the presence of arrhythmia, and the availability and cost associated with cardiac MRI. Level of Evidence C
      • 2.
        Balanced steady-state-free precession cine analysis has become the reference standard for volumetric and myocardial mass assessment of the LV. Where feasible, it should be used to assess children with HF. However, accuracy depends on standardization of analysis protocol and acquisition of adequate temporal and spatial resolution specific to the patient’s heart rate and size. Level of Evidence C

      RV systolic function
      • Lopez L.
      • Colan S.D.
      • Frommelt P.C.
      • et al.
      Recommendations for quantification methods during the performance of a pediatric echocardiogram: a report from the Pediatric Measurements Writing Group of the American Society of Echocardiography Pediatric and Congenital Heart Disease Council.

      Class IIa
      • 1.
        For the quantitative assessment of RV function by 2-D echocardiography, it is reasonable to use fractional area of change from the apical 4-chamber view together with tricuspid annular planar systolic excursion. Level of Evidence C
      • 2.
        TDI assessment of tricuspid annular motion is a useful technique for the assessment of RV longitudinal function and should be added in the quantitative assessment of RV function. Level of Evidence C
      Class IIb
      • 1.
        Due to methodologic variability and the load-dependency, the clinical use of RV myocardial performance index in the assessment of right HF is limited. Level of Evidence C
      • 2.
        RV strain analysis of RV longitudinal deformation is an emerging technique and requires further validation before routine use for the assessment of RV function. Level of Evidence C

      MRI RV function
      • Helbing W.A.
      • Bosch H.G.
      • Maliepaard C.
      • et al.
      Comparison of echocardiographic methods with magnetic resonance imaging for assessment of right ventricular function in children.
      • Mooij C.F.
      • de Wit C.J.
      • Graham D.A.
      • Powell A.J.
      • Geva T.
      Reproducibility of MRI measurements of right ventricular size and function in patients with normal and dilated ventricles.
      • Maceira A.M.
      • Prasad S.K.
      • Khan M.
      • Pennell D.J.
      Reference right ventricular systolic and diastolic function normalized to age, gender and body surface area from steady-state free precession cardiovascular magnetic resonance.

      Class IIa
      • 1.
        Assessment of RV size and EF by MRI is considered the clinical reference for the assessment of RV function in patients with RV failure. Restricted access, the need for general anesthesia or sedation in infants and young children, and costs remain important limitations. Level of Evidence C

      RV diastolic function

      Class IIb
      • 1.
        Doppler echocardiography can be used for the assessment of RV diastolic function, although criteria for grading and assessment of filling pressures are still poorly validated. Level of Evidence C
      • 2.
        Different MRI techniques are available for studying RV diastolic dysfunction, but their clinical utility still needs to be evaluated. Level of Evidence C

      Single-ventricle echo size and function

      Class IIb
      • 1.
        Quantitative techniques, such as fractional area of change, EF, annular excursion, and TDI for serial follow-up may be used, but good data regarding the prognostic value of observed changes are not available. Level of Evidence C

      Single-ventricle MRI size and function
      • Margossian R.
      • Schwartz M.L.
      • Prakash A.
      • et al.
      Comparison of echocardiographic and cardiac magnetic resonance imaging measurements of functional single ventricular volumes, mass, and ejection fraction (from the Pediatric Heart Network Fontan Cross-Sectional Study).

      Class IIa
      • 1.
        Cardiac MRI is the reference standard for volumetric analysis of the single ventricle. Larger studies are required to define acceptable ranges of end-diastolic or end-systolic volume in these patients. Level of Evidence B

      Exercise testing
      • Giardini A.
      • Fenton M.
      • Andrews R.E.
      • Derrick G.
      • Burch M.
      Peak oxygen uptake correlates with survival without clinical deterioration in ambulatory children with dilated cardiomyopathy.
      • Canter C.E.
      • Shaddy R.E.
      • Bernstein D.
      • et al.
      Indications for heart transplantation in pediatric heart disease: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young.

      Class IIa
      • 1.
        Metabolic exercise testing with a measurement of peak Vo2 consumption2, if feasible, should be part of the assessment of cardiomyopathy patients with HF. Level of Evidence C
      • 2.
        A peak Vo2 consumption of < 50% predicted for age and sex in patients with Stage C HF associated with severe limitation in exercise and activity may form the basis for consideration of heart transplantation. Level of Evidence C

      Sleep study
      • Nadar S.
      • Prasad N.
      • Taylor R.S.
      • Lip G.Y.
      Positive pressure ventilation in the management of acute and chronic cardiac failure: a systematic review and meta-analysis.

      Class IIa
      • 1.
        Children with HF and a history consistent with sleep apnea should undergo evaluation for sleep disorder breathing. Level of Evidence C

      Ambulatory monitoring
      • Pahl E.
      • Sleeper L.A.
      • Canter C.E.
      • et al.
      Incidence of and risk factors for sudden cardiac death in children with dilated cardiomyopathy: a report from the Pediatric Cardiomyopathy Registry.
      • Rosenthal D.N.
      • Dubin A.M.
      • Chin C.
      • Falco D.
      • Gamberg P.
      • Bernstein D.
      Outcome while awaiting heart transplantation in children: a comparison of congenital heart disease and cardiomyopathy.
      • Sarasin F.P.
      • Carballo D.
      • Slama S.
      • Louis-Simonet M.
      Usefulness of 24-h Holter monitoring in patients with unexplained syncope and a high likelihood of arrhythmias.

      Class I
      • 1.
        In a pediatric HF patient who presents with palpitations or syncope, some form of ambulatory monitoring should be considered to achieve a specific diagnosis and drive further management decisions. Less frequent symptoms may require use of longer-term event monitors. Level of Evidence C
      Class IIa
      • 1.
        In pediatric HF patients with a high risk of developing atrial or ventricular arrhythmias or heart block, regular ambulatory monitoring should be considered. This would include patients after a Fontan palliation, any form of atrial switch procedure, heterotaxy (isomeric) syndromes, congenitally corrected transposition of the great arteries, or cardiomyopathy (HCM, DCM, RCM, and LVNC). Level of Evidence C
      • 2.
        In asymptomatic pediatric HF patients, there are no data to support the timing and frequency of regular ambulatory monitoring for arrhythmias; however, intermittent screening for asymptomatic arrhythmias should be considered. Level of Evidence C

      Cardiac catheterization
      • Rosenthal D.
      • Chrisant M.R.K.
      • Edens E.
      • et al.
      International Society for Heart and Lung Transplantation: practice guidelines for management of heart failure in children.
      • Feltes T.F.
      • Bacha E.
      • Beekman R.H.
      • et al.
      Indications for cardiac catheterization and intervention in pediatric cardiac disease: a scientific statement from the American Heart Association.
      • Hunt S.A.
      • Abraham W.T.
      • Chin M.H.
      • et al.
      ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
      • Cooper L.T.
      • Baughman K.L.
      • Feldman A.M.
      • et al.
      The role of endomyocardial biopsy in the management of cardiovascular disease: a scientific statement from the American Heart Association, the American College of Cardiology, and the European Society of Cardiology.
      • Hauck A.J.
      • Kearney D.L.
      • Edwards W.D.
      Evaluation of postmortem endomyocardial biopsy specimens from 38 patients with lymphocytic myocarditis: implications for role of sampling error.

      Class IIa
      • 1.
        EMB should not be performed in clinically diagnosed myocarditis with minimal symptoms and mild dysfunction or rapid normalization of function. Level of Evidence C
      • 2.
        It is reasonable for cardiac catheterization to be performed if increased pulmonary resistance is suspected to measure the PVR and reversibility of pulmonary hypertension in patients with CHD and HF. Level of Evidence B
      Class IIb
      • 1.
        Cardiac catheterization and EMB can be considered for the assessment of unexplained cardiomyopathy or myocarditis if non-invasive testing does not yield a diagnosis. Level of Evidence C
      • 2.
        Cardiac catheterization and EMB is reasonable in the setting of suspected AVC. Level of Evidence C
      • 3.
        Cardiac catheterization and EMB is reasonable in pediatric patients presenting with HF when a specific diagnosis is suspected that would influence therapy. Level of Evidence C
      • 4.
        Cardiac catheterization may be considered to determine PVR and reversibility after medical therapy has been optimized in patients with cardiomyopathy if they are stable enough to undergo testing, but the necessity is controversial outside of consideration for transplantation. Level of Evidence C
      • 5.
        It is reasonable for EMB to be performed in the setting of unexplained new-onset HF associated with hemodynamic compromise, ventricular arrhythmia, or heart block where there is failure to respond to medical therapy. Level of Evidence B

      Assessment of PVR
      • Masuyama T.
      • Kodama K.
      • Kitabatake A.
      • Sato H.
      • Nanto S.
      • Inoue M.
      Continuous-wave Doppler echocardiographic detection of pulmonary regurgitation and its application to noninvasive estimation of pulmonary artery pressure.
      • Benza R.
      • Biederman R.
      • Murali S.
      • Gupta H.
      Role of cardiac magnetic resonance imaging in the management of patients with pulmonary arterial hypertension.

      Class IIa
      • 1.
        Doppler-derived estimations of right heart pressures (right ventricular systolic pressure and pulmonary artery pressures) can be obtained for assessment and longitudinal follow-up of HF patients to monitor response to treatment, progression of disease, and contribute to decision making about more invasive assessment of PVR for the purpose of decision-making around medical and/or surgical interventions including transplantation. Level of Evidence C
      • 2.
        It is reasonable for cardiac catheterization to be performed to assess PVR and reversibility in patients with CHD and HF. Level of Evidence B
      Class IIb
      • 1.
        The role of MRI in the assessment of PVR in children with HF requires further study. Level of Evidence C

      Tachycardia-induced cardiomyopathy
      • Garson A.
      • Gillette P.C.
      • McNamara D.G.
      Supraventricular tachycardia in children: clinical features, response to treatment, and long-term follow-up in 217 patients.
      • Donghua Z.
      • Jian P.
      • Zhongbo X.
      • et al.
      Reversal of cardiomyopathy in patients with congestive heart failure secondary to tachycardia.

      Class IIa
      • 1.
        Electrophysiology testing or long-term monitoring can be useful in pediatric patients with presyncope or syncope with at least moderately impaired LV function. Level of Evidence C
      • 2.
        Tachycardia-induced cardiomyopathy should be considered in any patient presenting with DCM because it is potentially reversible with appropriate intervention. Level of Evidence B
      Class IIb
      • 1.
        Programmed ventricular stimulation may be helpful in specific situations, such as in patients with HF and syncope, but does not appear to have a routine role in risk stratification in the pediatric patient with HF. Level of Evidence C

      Pharmacologic treatment of chronic, reduced EF (systolic HF) recommendations

      Chairs: David N. Rosenthal and Robert Shaddy

      Diuretics
      • Hunt S.A.
      • Abraham W.T.
      • Chin M.H.
      • et al.
      2009 Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the International Society for Heart and Lung Transplantation.
      • Parker J.O.
      The effects of oral ibopamine in patients with mild heart failure--a double blind placebo controlled comparison to furosemide. The Ibopamine Study Group.

      Class I
      • 1.
        Patients with fluid retention associated with ventricular dysfunction (HF Stage C) should be treated with diuretics to achieve a euvolemic state. Level of Evidence C

      ACE inhibitors
      • Li J.S.
      • Colan S.D.
      • Sleeper L.A.
      • et al.
      Lessons learned from a pediatric clinical trial: the Pediatric Heart Network angiotensin-converting enzyme inhibition in mitral regurgitation study.
      • Lewis A.B.
      • Chabot M.
      The effect of treatment with angiotensin-converting enzyme inhibitors on survival of pediatric patients with dilated cardiomyopathy.
      • Kantor P.F.
      • Abraham J.R.
      • Dipchand A.I.
      • Benson L.N.
      • Redington A.N.
      The impact of changing medical therapy on transplantation-free survival in pediatric dilated cardiomyopathy.
      • Duboc D.
      • Meune C.
      • Lerebours G.
      • Devaux J.-Y.
      • Vaksmann G.
      • Bécane H.-M.
      Effect of perindopril on the onset and progression of left ventricular dysfunction in Duchenne muscular dystrophy.
      • Duboc D.
      • Meune C.
      • Pierre B.
      • et al.
      Perindopril preventive treatment on mortality in Duchenne muscular dystrophy: 10 years’ follow-up.

      Class1
      • 1.
        For the treatment of symptomatic left ventricular dysfunction (HF Stage C), ACE inhibitors should be routinely used unless there is a specific contraindication. These medications should be started at low doses and should be up-titrated to a maximum tolerated safe dose. Level of Evidence B
      Class IIa
      • 1.
        For the treatment of asymptomatic left ventricular dysfunction (HF Stage B), ACE inhibitors should be routinely used unless there is a specific contraindication. Level of Evidence B
      • 2.
        ACE inhibitor therapy should be considered for individuals with a diagnosis of Duchenne muscular dystrophy unless there is a specific contraindication, although the optimal age of institution of therapy is unclear. Level of Evidence B
      Class IIb
      • 1.
        ACE inhibitor therapy should not be routinely instituted for all patients with single-ventricle CHD, but could be considered in specific cases such as in situations of valve regurgitation or ventricular dysfunction. Level of Evidence B

      β-Receptor antagonists
      • Packer M.
      • Coats A.J.
      • Fowler M.B.
      • et al.
      Effect of carvedilol on survival in severe chronic heart failure.
      • Shaddy R.E.
      • Boucek M.M.
      • Hsu D.T.
      • et al.
      Carvedilol for children and adolescents with heart failure: a randomized controlled trial.
      • Albers S.
      • Meibohm B.
      • Mir T.S.
      • Läer S.
      Population pharmacokinetics and dose simulation of carvedilol in paediatric patients with congestive heart failure.

      Class IIa
      • 1.
        Following adult HF guidelines, it is reasonable to consider β-blockers in symptomatic children with systemic LV systolic dysfunction, particularly if the systemic ventricle has a LV morphology. Therapy should start at a small dose and slowly up-titrate. Level of Evidence B
      • 2.
        Following adult HF guidelines, it is reasonable to consider β-blockers in asymptomatic children with systemic LV systolic dysfunction. Therapy should start at a small dose and slowly up-titrate. Level of Evidence B

      Mineralocorticoid antagonists
      • Pitt B.
      • Zannad F.
      • Remme W.J.
      • et al.
      The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators.

      Class I
      • 1.
        Following adult HF guidelines, it is reasonable to consider aldosterone antagonists in children with systemic LV dysfunction. Level of Evidence C

      Angiotensin receptor antagonists
      • Pitt B.
      • Poole-Wilson P.A.
      • Segal R.
      • et al.
      Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial--the Losartan Heart Failure Survival Study ELITE II.

      Class IIa
      • 1.
        Similar to adults, angiotensin receptor blockers are generally reserved for those children with systemic ventricular systolic dysfunction who would benefit from renin-angiotensin-aldosterone– system blockade but are intolerant of ACE inhibitors. Level of Evidence C

      Digoxin and cardiac glycosides
      • Lindenfeld J.
      • Albert N.M.
      • Boehmer J.P.
      • et al.
      HFSA 2010 comprehensive heart failure practice guideline.
      Digitalis Investigation Group
      The effect of digoxin on mortality and morbidity in patients with heart failure.

      Class I
      • 1.
        Digoxin is not recommended for children with asymptomatic LV dysfunction because no survival benefit was seen with digoxin in adults with HF and low EF. Level of Evidence C
      Class IIa
      • 1.
        Digoxin may be used to relieve symptoms in children with symptomatic HF and low EF. Doses targeting lower serum digoxin concentrations (e.g., 0.5–0.9 ng/ml) should be considered with attention to dose reductions in patients on carvedilol and amiodarone or those who have or are at risk for renal dysfunction. Level of Evidence C

      Hydralazine combination with isosorbide dinitrate
      • Cohn J.N.
      • Archibald D.G.
      • Ziesche S.
      • et al.
      Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study.

      Class III
      • 1.
        The use of combination therapy of hydralazine and isosorbide dinitrate is not recommended in pediatric HF. Level of Evidence C

      Anti-arrhythmic medications
      • Lindenfeld J.
      • Albert N.M.
      • Boehmer J.P.
      • et al.
      HFSA 2010 comprehensive heart failure practice guideline.
      • Pahl E.
      • Sleeper L.A.
      • Canter C.E.
      • et al.
      Incidence of and risk factors for sudden cardiac death in children with dilated cardiomyopathy: a report from the Pediatric Cardiomyopathy Registry.

      Class IIb
      • 1.
        The use of anti-arrhythmic medications may be warranted in select cases where arrhythmias persist after normalization of electrolyte disturbances or metabolic issues (i.e., hyperthyroidism) and the arrhythmias are poorly tolerated. Level of Evidence C
      Class III
      • 1.
        Anti-arrhythmic medications should not be used routinely in the management of children with HF with low EF. Level of Evidence C

      Statin therapy

      Class III
      • 1.
        Treatment of HF with statin therapy is not indicated in pediatric HF patients. Level of Evidence C

      Renin inhibitors

      Class III
      • 1.
        Direct renin inhibitors cannot be recommended for the treatment of HF in children. Level of Evidence C

      Anticoagulants
      • Massie B.M.
      • Collins J.F.
      • Ammon S.E.
      • et al.
      Randomized trial of warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) trial.
      • Homma S.
      • Thompson J.L.P.
      • Pullicino P.M.
      • et al.
      Warfarin and aspirin in patients with heart failure and sinus rhythm.

      Class I
      • 1.
        Patients with intracardiac thrombus should receive anticoagulation with heparin or warfarin. Level of Evidence B
      Class IIa
      • 1.
        For patients with a history of thrombus or a thromboembolic event who have an EF < 25% (fractional shortening < 15%), anti-coagulation with heparin or warfarin should be considered. Level of Evidence C
      • 2.
        Extrapolating from the strong data in the adult HF population, children with low EF and persistent or uncontrolled paroxysmal atrial fibrillation or flutter should receive anti-coagulation with heparin or warfarin. Level of Evidence C
      Class III
      • 1.
        No recommendation can be made regarding the use of anti-coagulation or anti-platelet therapy in patients with reduced EF and no history of thrombus or thromboembolic event, because there is insufficient evidence to justify a recommendation. Level of Evidence C

      Nesiritide

      Publication Committee for the VMAC Investigators (Vasodilatation in the Management of Acute CHF). Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 2002;287:1531–1540 (erratum in JAMA 2002;288:577).

      • Sackner-Bernstein J.D.
      • Kowalski M.
      • Fox M.
      • Aaronson K.
      Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials.

      Class IIb
      • 1.
        The use of nesiritide cannot be recommended for routine use in acute HF in children, although it may be considered in select situations where other interventions to lower central venous pressure have been unsuccessful. Level of Evidence C

      Positive inotropic agents
      • Berg A.M.
      • Snell L.
      • Mahle W.T.
      Home inotropic therapy in children.
      • Hunt S.A.
      • Abraham W.T.
      • Chin M.H.
      • et al.
      2009 focused update incorporated into the ACC/AHA 2005 guidelines for the diagnosis and management of heart failure in adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the International Society for Heart and Lung Transplantation.

      Class IIa
      • 1.
        Inotropic therapy may be considered for symptomatic relief in the palliative setting. Level of Evidence C
      Class III
      • 1.
        On the basis of a lack of any pediatric data and lack of data supporting improved outcomes in adults, use of intermittent or chronic inotropic therapy, other than as a bridge to transplant, is not recommended. Level of Evidence C

      Vasopressin receptor antagonists
      • Konstam M.A.
      • Gheorghiade M.
      • Burnett J.C.
      • et al.
      Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial.
      • Valania G.
      • Singh M.
      • Slawsky M.T.
      Targeting hyponatremia and hemodynamics in acute decompensated heart failure: is there a role for vasopressin antagonists?.

      Class III
      • 1.
        Vasopressin receptor antagonists cannot be recommended for the routine treatment of chronic HF in children. Level of Evidence C

      Pharmacologic treatment of “preserved” EF (diastolic heart failure) recommendations

      Chairs: David N Rosenthal and Robert Weintraub

      Diuretics
      • Senzaki H.
      • Kamiyama M.
      • Masutani S.
      • et al.
      Efficacy and safety of torasemide in children with heart failure.

      Class I
      • 1.
        Use of diuretics to establish a clinically euvolemic state is recommended for children with HFpEF. Level of Evidence C
      • 2.
        In patients with HFpEF, close monitoring of renal function and blood pressure should be performed during initiation and up-titration of diuretic therapy. Level of Evidence C
      Class IIa
      • 1.
        Treatment of systemic hypertension in patients with HFpEF is recommended to prevent disease progression. Although no particular class of medication is favored, diuretics may be considered for this purpose. Level of Evidence C

      ACE inhibitors and angiotensin receptor blockade
      • Shah R.V.
      • Desai A.S.
      • Givertz M.M.
      The effect of renin-angiotensin system inhibitors on mortality and heart failure hospitalization in patients with heart failure and preserved ejection fraction: a systematic review and meta-analysis.
      • Yusuf S.
      • Pfeffer M.A.
      • Swedberg K.
      • et al.
      Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial.
      • Massie B.M.
      • Carson P.E.
      • McMurray J.J.
      • et al.
      Irbesartan in patients with heart failure and preserved ejection fraction.

      Class IIb
      • 1.
        Routine use of renin-angiotensin antagonists is not recommended in HFpEF, unless there is an additional indication for use of these classes of medications such as hypertension. Level of Evidence C
      • 2.
        Renin-angiotensin antagonists may be used for control of hypertension in HFpEF, but careful monitoring of hemodynamics and renal function is indicated due to the enhanced risk of hypotension and renal toxicity. Level of Evidence C

      Calcium channel antagonists
      • Setaro J.F.
      • Zaret B.L.
      • Schulman D.S.
      • Black H.R.
      • Soufer R.
      Usefulness of verapamil for congestive heart failure associated with abnormal left ventricular diastolic filling and normal left ventricular systolic performance.
      • Hung M.J.
      • Cherng W.J.
      • Wang C.H.
      • Kuo L.T.
      Effects of verapamil in normal elderly individuals with left ventricular diastolic dysfunction.

      Class III
      • 1.
        Use of calcium channel blockers is not recommended for treatment of HFpEF in children, unless there is an additional indication. Level of Evidence C

      Mineralocorticoid/aldosterone receptor antagonists
      • Edelmann F.
      • Wachter R.
      • Schmidt A.G.
      • et al.
      Effect of spironolactone on diastolic function and exercise capacity in patients with heart failure with preserved ejection fraction: the Aldo-DHF randomized controlled trial.

      Class IIb
      • 1.
        In children with HFpEF, aldosterone blockade with either spironolactone or eplerenone is not recommended. Level of Evidence C

      Phosphodiesterase inhibitors
      • Redfield M.M.
      • Chen H.H.
      • Borlaug B.A.
      • et al.
      Effect of phosphodiesterase-5 inhibition on exercise capacity and clinical status in heart failure with preserved ejection fraction: a randomized clinical trial.
      • Guazzi M.
      • Vicenzi M.
      • Arena R.
      • Guazzi M.D.
      Pulmonary hypertension in heart failure with preserved ejection fraction: a target of phosphodiesterase-5 inhibition in a 1-year study.

      Class IIb
      • 1.
        Use of phosphodiesterase inhibitors is not recommended for treatment of HFpEF in children, unless there is an additional indication for use of these classes of medications such as pulmonary hypertension. Level of Evidence C

      Digoxin and other digitalis glycosides

      Class III
      • 1.
        Use of digoxin is not recommended for treatment of HFpEF in children, unless there is an additional indication such as arrhythmia requiring atrial rate control. Level of Evidence C

      Positive inotropic agents

      Class III
      • 1.
        Intravenous β-agonists, such as dopamine, dobutamine, and epinephrine, are not indicated for treatment of HFpEF. Level of Evidence C

      Pulmonary vasodilators
      • Califf R.M.
      • Adams K.F.
      • McKenna W.J.
      • et al.
      A randomized controlled trial of epoprostenol therapy for severe congestive heart failure: the Flolan International Randomized Survival Trial (FIRST).

      Class III
      • 1.
        The use of prostaglandins and endothelin receptor antagonists to treat secondary pulmonary hypertension in children with HFpEF is not supported by current evidence. Level of Evidence C

      Electrophysiology intervention recommendations

      Chairs: David N. Rosenthal and Anne M. Dubin

      Pacemaker therapy
      • Lazarus A.
      • Varin J.
      • Babuty D.
      • Anselme F.
      • Coste J.
      • Duboc D.
      Long-term follow-up of arrhythmias in patients with myotonic dystrophy treated by pacing: a multicenter diagnostic pacemaker study.
      • Janousek J.
      • van Geldorp I.E.
      • Krupickova S.
      • et al.
      Permanent cardiac pacing in children: choosing the optimal pacing site: a multicenter study.

      Class I
      • 1.
        Permanent pacemaker implantation is recommended for advanced second- or third-degree atrioventricular block associated with ventricular dysfunction. Level of Evidence B
      Class IIa
      • 1.
        LV apical pacing can be useful in epicardial ventricular pacing systems. Technical considerations may require alternate ventricular lead placement. Level of Evidence B

      Cardiac resynchronization therapy
      • Dubin A.M.
      • Janousek J.
      • Rhee E.
      • et al.
      Resynchronization therapy in pediatric and congenital heart disease patients: an international multicenter study.
      • Janousek J.
      • Gebauer R.A.
      • Abdul-Khaliq H.
      • et al.
      Cardiac resynchronisation therapy in paediatric and congenital heart disease: differential effects in various anatomical and functional substrates.
      • Cecchin F.
      • Frangini P.A.
      • Brown D.W.
      • et al.
      Cardiac resynchronization therapy (and multisite pacing) in pediatrics and congenital heart disease: five years experience in a single institution.

      Class IIa
      • 1.
        CRT can be useful for pediatric patients with a systemic LV with an EF < 35%, complete left bundle branch block pattern, QRS duration (native or paced) > ULN for age, NYHA Class II-IV on GDMT. Level of Evidence B
      Class IIb
      • 1.
        CRT may be considered for pediatric patients with a systemic RV, with an EF < 35%, complete right bundle branch block pattern, QRS duration (native or paced) > ULN for age, NYHA Class II-IV on GDMT. Level of Evidence C
      • 2.
        CRT may be considered for pediatric patients with a single ventricle, with an EF < 35%, complete bundle branch pattern, QRS duration (native or paced) > ULN for age, NYHA Class II-V on GDMT. Level of Evidence C

      ICD therapy
      • Pahl E.
      • Sleeper L.A.
      • Canter C.E.
      • et al.
      Incidence of and risk factors for sudden cardiac death in children with dilated cardiomyopathy: a report from the Pediatric Cardiomyopathy Registry.
      • Moss A.J.
      • Hall W.J.
      • Cannom D.S.
      • et al.
      Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators.
      • Rhee E.K.
      • Canter C.E.
      • Basile S.
      • Webber S.A.
      • Naftel D.C.
      Sudden death prior to pediatric heart transplantation: would implantable defibrillators improve outcome?.
      A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias
      The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators.

      Class I
      • 1.
        ICD implantation is recommended in the pediatric survivor of cardiac arrest after evaluation to define the cause of the event and to exclude any reversible/treatable causes. Level of Evidence B
      Class IIa
      • 1.
        ICD implantation can be useful in the pediatric patient with unexplained syncope and at least moderate LV dysfunction and DCM. Level of Evidence C
      • 2.
        ICD implantation can be useful for adolescent patients with HCM who have 1 or more major risk factors for SCD. In younger patients, the risk/benefit ratio must be considered due to technical considerations. Level of Evidence C
      • 3.
        ICD implantation can be useful for the prevention of SCD in adolescent patients with AVC who have 1 or more risk factors for SCD. In younger patients, the risk/benefit ratio must be considered due to technical considerations. Level of Evidence C
      • 4.
        ICD therapy can be useful in adolescent patients with a familial cardiomyopathy associated with SCD. In younger patients, the risk/benefit ratio must be considered due to technical considerations. Level of Evidence C
      Class IIb
      • 1.
        ICD therapy may be considered in pediatric patients with DCM who have an LVEF < 35% and who are in NYHA Class II or III. Level of Evidence C
      • 2.
        ICD implantation may be considered for patients with CHD with syncope in the presence of ventricular dysfunction. Level of Evidence C
      • 3.
        ICD therapy may be considered in adolescent patients with LVNC and moderately depressed ventricular function. In younger patients, the risk/benefit ratio must be considered due to technical considerations. Level of Evidence C
      • 4.
        ICD therapy may be considered in non-hospitalized pediatric patients with non-sustained or sustained ventricular tachycardia who required a VAD. Level of Evidence C

      Ablation therapy

      Class I
      • 1.
        Ablation therapy is recommended in the pediatric patient with tachycardia-induced cardiomyopathy when medical therapy fails. Level of Evidence B
      Class IIa
      • 1.
        Ablation therapy can be useful as primary therapy in the adolescent patient with tachycardia-induced cardiomyopathy. Level of Evidence B
      Class IIb
      • 1.
        Ablation therapy may be considered in the pediatric patient with frequent premature ventricular contraction and cardiomyopathy of unknown etiology when medical therapy fails. Level of Evidence B

      Mechanical circulatory support recommendations

      Chairs: David N. Rosenthal and David Morales

      Durable VAD system
      • Almond C.S.
      • Morales D.L.
      • Blackstone E.H.
      • et al.
      Berlin Heart EXCOR pediatric ventricular assist device for bridge to heart transplantation in US children.
      • Fraser C.D.
      • Jaquiss R.D.B.
      • Rosenthal D.N.
      • et al.
      Prospective trial of a pediatric ventricular assist device.
      • Hetzer R.
      • Alexi-Meskishvili V.
      • Weng Y.
      • et al.
      Mechanical cardiac support in the young with the Berlin Heart EXCOR pulsatile ventricular assist device: 15 years’ experience.

      Class I
      • 1.
        Implantation of a durable VAD system should be considered as a bridge to transplantation for children who are unable to be weaned from inotropic support and are showing early, reversible dysfunction of at least 1 other major organ system. Level of Evidence C
      Class IIa
      • 1.
        Management of chronic VAD devices in children, including anticoagulation medications, should be performed by a specialized team with appropriate expertise and focus. Level of Evidence C
      Class IIb
      • 1.
        Implantation of a chronic VAD system for children who are not eligible for transplantation may be considered as long-term support (destination therapy), provided a system is available that permits discharge to home with regular outpatient follow-up. Level of Evidence C

      Temporary circulatory support
      • Teele S.A.
      • Allan C.K.
      • Laussen P.C.
      • Newburger J.W.
      • Gauvreau K.
      • Thiagarajan R.R.
      Management and outcomes in pediatric patients presenting with acute fulminant myocarditis.
      • Kane D.A.
      • Thiagarajan R.R.
      • Wypij D.
      • et al.
      Rapid-response extracorporeal membrane oxygenation to support cardiopulmonary resuscitation in children with cardiac disease.
      • Hunkeler N.M.
      • Canter C.E.
      • Donze A.
      • Spray T.L.
      Extracorporeal life support in cyanotic congenital heart disease before cardiovascular operation.

      Class IIa
      • 1.
        For a child in cardiac arrest or cardiogenic shock with pulmonary compromise, ECMO should be considered for emergency cardiovascular support, as a temporizing measure as a bridge to recovery of function. Level of Evidence C
      • 2.
        For a child with isolated cardiac failure that is believed to be reversible, ECMO or a temporary VAD may be considered as a temporizing measure as a bridge to recovery of function. If recovery does not occur, then transition to a chronic VAD for bridge to transplantation or for destination therapy (if child can receive a second- or third-generation VAD), is reasonable. Level of Evidence C
      • 3.
        For a child with cardiogenic shock that is not believed to be due to a reversible underlying cause, consideration should be given to use of a temporary VAD or ECMO for resuscitation of end-organ function rather than directly implanting a chronic VAD system. Level of Evidence C

      BiVAD support
      • Almond C.S.
      • Morales D.L.
      • Blackstone E.H.
      • et al.
      Berlin Heart EXCOR pediatric ventricular assist device for bridge to heart transplantation in US children.
      • Kirklin J.K.
      • Naftel D.C.
      • Kormos R.L.
      • et al.
      The Fourth INTERMACS Annual Report: 4,000 implants and counting.
      • Baldwin J.T.
      • Borovetz H.S.
      • Duncan B.W.
      • Gartner M.J.
      • Jarvik R.K.
      • Weiss W.J.
      The national heart, lung, and blood institute pediatric circulatory support program: a summary of the 5-year experience.

      Class IIb
      • 1.
        Use of BiVAD support should be minimized, reserving BiVAD support for patients who appear unlikely to achieve adequate hemodynamics from LVAD support alone. However, decision making for this remains highly individualized, with no broadly useful risk-stratification scheme available. Level of Evidence C

      VAD support in the univentricular heart
      • Booth K.L.
      • Roth S.J.
      • Thiagarajan R.R.
      • Almodovar M.C.
      • Del Nido P.J.
      • Laussen P.C.
      Extracorporeal membrane oxygenation support of the Fontan and bidirectional Glenn circulations.
      • Allan C.K.
      • Thiagarajan R.R.
      • del Nido P.J.
      • Roth S.J.
      • Almodovar M.C.
      • Laussen P.C.
      Indication for initiation of mechanical circulatory support impacts survival of infants with shunted single-ventricle circulation supported with extracorporeal membrane oxygenation.
      • Russo P.
      • Wheeler A.
      • Russo J.
      • Tobias J.D.
      Use of a ventricular assist device as a bridge to transplantation in a patient with single ventricle physiology and total cavopulmonary anastomosis.
      • Prêtre R.
      • Häussler A.
      • Bettex D.
      • Genoni M.
      Right-sided univentricular cardiac assistance in a failing Fontan circulation.

      Class I
      • 1.
        For neonates with univentricular circulation who require circulatory support for a reversible cause, ECMO should be considered. Level of Evidence C
      Class IIb
      • 1.
        For neonates with univentricular circulation who require long-term support as a bridge to transplantation, ECMO should only be deployed after careful evaluation of anticipated waiting list times and with consideration to donor scarcity. Level of Evidence B
      • 2.
        Use of a long-term VAD for circulatory support may be considered in a neonate or older child with failed univentricular circulation, but outcomes with this support are poor for neonates and moderate for older children. Level of Evidence B
      Class III
      • 1.
        Use of a long-term VAD may be considered for circulatory support in a neonate with univentricular circulation who has failed to wean from cardiopulmonary bypass after palliative surgery but is not routinely recommended due to poor outcomes with this support. Level of Evidence B

      Cardiac recovery
      • Birks E.J.
      • Tansley P.D.
      • Hardy J.
      • et al.
      Left ventricular assist device and drug therapy for the reversal of heart failure.

      Class IIb
      • 1.
        Children who are supported on a chronic VAD system may be considered for a recovery protocol and weaning from VAD if recovery of cardiac function is documented. Level of Evidence C

      Comorbidity recommendations

      Chairs: David N. Rosenthal and Melanie Everitt

      Anemia
      • Ghali J.K.
      • Anand I.S.
      • Abraham W.T.
      • et al.
      Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia.
      • Hunt S.A.
      ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guideli.
      • Mahle W.T.
      • Berg A.M.
      • Kanter K.R.
      Red blood cell transfusions in children awaiting heart transplantation.

      Class I
      • 1.
        At the time of diagnosis and at ongoing regular intervals thereafter, the presence of anemia should be determined through measurement of plasma hemoglobin or hematocrit levels. Level of Evidence C
      • 2.
        Iron deficiency as a treatable cause of anemia in the patient with HF should be sought by obtaining iron studies (ferritin with transferrin saturation). Level of Evidence C
      • 3.
        It is reasonable to consider the use of intravenous iron to treat iron-deficiency anemia in pediatric patients with HF. Level of Evidence C
      Class IIa
      • 1.
        It is reasonable to consider the use of erythropoiesis-stimulating agents to treat anemia in pediatric patients with HF if anemia persists once iron stores are replete. Level of Evidence C
      • 2.
        Restrictive transfusion thresholds appear to have no detrimental effect on outcomes and should be considered in the stable patient to reduce overall blood product exposure. Level of Evidence C
      Class III
      • 1.
        There is no evidence to support the use of intravenous iron or erythropoiesis-stimulating agents for the prevention of HF-associated anemia in children. Level of Evidence C

      Renal dysfunction
      • Tavazzi L.
      • Senni M.
      • Metra M.
      • et al.
      Multicenter prospective observational study on acute and chronic heart failure: one-year follow-up results of IN-HF (Italian Network on Heart Failure) outcome registry.
      • Ricci Z.
      • Di Nardo M.
      • Iacoella C.
      • Netto R.
      • Picca S.
      • Cogo P.
      Pediatric RIFLE for acute kidney injury diagnosis and prognosis for children undergoing cardiac surgery: a single-center prospective observational study.
      • Akcan-Arikan A.
      • Zappitelli M.
      • Loftis L.L.
      • Washburn K.K.
      • Jefferson L.S.
      • Goldstein S.L.
      Modified RIFLE criteria in critically ill children with acute kidney injury.

      Class I
      • 1.
        At the time of the HF diagnosis and at ongoing regular intervals, including after changes in medical therapy, the presence and severity of renal dysfunction should be determined. Level of Evidence B
      • 2.
        Management of acute kidney injury should include strict recording of fluid balance, daily weight measurements, and calculation of the blood urea nitrogen/creatinine ratio to avoid poor renal perfusion secondary to dehydration. Level of Evidence C
      • 3.
        Worsening renal function should prompt a review and possible adjustment of medications known to impair renal perfusion or function and medications that are renally excreted. Level of Evidence A
      Class IIa
      • 1.
        The modified Schwartz formula is reasonable to use in calculating glomerular filtration rate in pediatric patients aged older than 2 years. Level of Evidence B

      Airway and parenchymal respiratory morbidity
      • Guillemaud J.P.
      • El-Hakim H.
      • Richards S.
      • Chauhan N.
      Airway pathologic abnormalities in symptomatic children with congenital cardiac and vascular disease.
      • Healy F.
      • Hanna B.D.
      • Zinman R.
      Pulmonary complications of congenital heart disease.

      Class I
      • 1.
        Chest X-ray imaging should be obtained in the pediatric HF patient who presents with new or worsening respiratory symptoms to evaluate for treatable pulmonary complications. Level of Evidence C
      • 2.
        Flexible bronchoscopy is a safe and effective first-line approach to diagnosing bronchial compression due to cardiomegaly as a cause for recurrent pneumonia or persistent atelectasis in the child with HF. Level of Evidence C
      • 3.
        Polysomnography should be performed in patients with signs and symptoms of sleep-related breathing disorders, especially when pulmonary hypertension is present. Level of Evidence C
      • 4.
        Pulmonary function testing should be used for detection and reversibility of obstructive-related breathing disorders, especially when pulmonary hypertension is present. Level of Evidence C
      • 5.
        Pulmonary function testing should be used for detection and reversibility of obstructive defects as well as for the diagnosis of restrictive lung disease. Level of Evidence C
      • 6.
        Exercise testing with metabolic studies should be used to determine a component of respiratory limitation to exercise in symptoms with HF. Level of Evidence C
      Class III
      • 1.
        During acute intercurrent pulmonary illness (i.e., pneumonia, asthma exacerbation, bronchitis), the abrupt discontinuation of β-blockers and ACE inhibitors is not indicated unless there is a life-threatening complication related to their use. Level of Evidence B
      • 2.
        Classical asthma medications, such as bronchodilators or corticosteroids, are generally not effective in the treatment of cardiac asthma. Level of Evidence B

      Infectious diseases
      • Pickering L.K.
      American Academy of Pediatrics
      Red Book: 2012 report of the Committee on Infectious Diseases.
      • Danziger-Isakov L.
      • Kumar D.
      Vaccination in solid organ transplantation.

      Class I
      • 1.
        Pediatric HF patients aged ≤ 24 months, who meet criteria for prophylaxis, should receive palivizumab to reduce the risk of respiratory syncytial virus lower respiratory tract disease using published guidelines. Level of Evidence A
      • 2.
        Immunizations reduce the incidence of respiratory infection, including community-acquired pneumonia and influenza. Children with HF should receive complete and age-appropriate immunizations, including pneumococcal conjugate/polysaccharide vaccines and an annual influenza vaccine. Annually updated vaccine schedules are provided by the Centers for Disease Control and Prevention. Level of Evidence A
      • 3.
        Children with HF who might require transplantation should have a pre-transplant assessment of routine vaccinations, including rotavirus and other live virus vaccines. Catch-up and/or accelerated vaccination schedules should be used to ensure complete immunization before transplant. Level of Evidence A
      • 4.
        Families, care givers, and close contacts of children with HF should receive all recommended vaccines, including a tetanus/diphtheria/pertussis immunization/booster and a yearly influenza vaccine. Level of Evidence A
      • 5.
        Because pediatric patients with HF are at increased risk for health care-associated infections due to severity of illness and treatment interventions, validated infection prevention measures to reduce the risk of nosocomial infections should be encouraged. Level of Evidence A

      Malnutrition and cachexia
      • Evans W.J.
      • Morley J.E.
      • Argilés J.
      • et al.
      Cachexia: a new definition.
      • Anker S.D.
      • Negassa A.
      • Coats A.J.
      • et al.
      Prognostic importance of weight loss in chronic heart failure and the effect of treatment with angiotensin-converting-enzyme inhibitors: an observational study.
      • Secker D.
      Promoting optimal monitoring of child growth in Canada: using the new WHO growth charts.

      Class IIa
      • 1.
        In the absence of clinical parameters to define cardiac cachexia in pediatrics, children plotting below the third percentile (–2 standard deviation) require further assessment, referral, or intervention for cachexia. Level of Evidence C
      • 2.
        Energy and nutrient intake and barriers to intake should be individually assessed regularly. Level of Evidence C
      Class III
      • 1.
        There is no evidence to support the routine use of vitamin and mineral supplements in children unless indicated to treat a specific, documented deficiency. Level of Evidence C

      Metabolic syndrome
      • Cubbon R.M.
      • Adams B.
      • Rajwani A.
      • et al.
      Diabetes mellitus is associated with adverse prognosis in chronic heart failure of ischaemic and non-ischaemic aetiology.
      • Weiss R.
      • Dziura J.
      • Burgert T.S.
      • et al.
      Obesity and the metabolic syndrome in children and adolescents.

      Class I
      • 1.
        The presence of obesity in pediatric patients with heart disease should prompt specific evaluation for metabolic syndrome and all other cardiovascular risk factors, including hypertension, dyslipidemia, insulin resistance, and liver disease. Level of Evidence A
      • 2.
        An intensive, multidisciplinary weight-reduction program and management of other identifiable risk factors should be initiated in pediatric patients with metabolic syndrome. Level of Evidence B

      Depression and psychologic functioning
      • Menteer J.
      • Beas V.N.
      • Chang J.C.
      • Reed K.
      • Gold J.I.
      Mood and health-related quality of life among pediatric patients with heart failure.
      • Menteer J.
      • Macey P.M.
      • Woo M.A.
      • Panigrahy A.
      • Harper R.M.
      Central nervous system changes in pediatric heart failure: a volumetric study.
      • Ozbaran B.
      • Kose S.
      • Yagdi T.
      • et al.
      Psychiatric evaluation of children and adolescents with left ventricular assist devices.

      Class I
      • 1.
        Children with HF should be screened for mood disorders, including anxiety, depression, adjustment disorder, and sleep disorder. Level of Evidence B
      • 2.
        The need for psychologic support should be discussed and provided as deemed appropriate before, immediately after, and during follow-up of children undergoing ICD and/or VAD implantation. Level of Evidence C

      Cognitive and psychosocial performance
      • Kindel S.J.
      • Miller E.M.
      • Gupta R.
      • et al.
      Pediatric cardiomyopathy: importance of genetic and metabolic evaluation.
      • Staniforth A.D.
      • Kinnear W.J.
      • Cowley A.J.
      Cognitive impairment in heart failure with Cheyne-Stokes respiration.
      • Bornstein R.A.
      • Starling R.C.
      • Myerowitz P.D.
      • Haas G.J.
      Neuropsychological function in patients with end-stage heart failure before and after cardiac transplantation.
      • Stein M.L.
      • Bruno J.L.
      • Konopacki K.L.
      • Kesler S.
      • Reinhartz O.
      • Rosenthal D.
      Cognitive outcomes in pediatric heart transplant recipients bridged to transplantation with ventricular assist devices.

      Class I
      • 1.
        Assessments of overall intelligence, speech/language, and motor development should be performed at least yearly in all patients with chronic HF. Early intervention and school accommodations are recommended for those with social and/or cognitive deficits. Level of Evidence C
      • 2.
        Referral to a developmental specialist is recommended in all patients with chronic HF who are not meeting developmental milestones or who are demonstrating deficits in social or cognitive development. Level of Evidence C
      • 3.
        Infants with chronic HF should be referred to appropriate early intervention programs, especially those with coexisting CHD. Level of Evidence C
      • 4.
        School attendance and age-appropriate developmentally stimulating activities should be provided for medically stable patients with congestive HF, both in the inpatient and outpatient setting. Level of Evidence C
      Class IIa
      • 1.
        Brain imaging should be considered in patients with chronic HF and deficits in social and/or cognitive performance, but does not need to be performed routinely. Level of Evidence B
      • 2.
        Brain imaging should be considered in patients with destination VAD therapy and deficits in social and/or cognitive performance, but does not need to be performed routinely. Level of Evidence C

      Exercise training and activity recommendations
      • Rees K.
      • Taylor R.S.
      • Singh S.
      • Coats A.J.S.
      • Ebrahim S.
      Exercise based rehabilitation for heart failure.
      • Guimarães G.V.
      • Bellotti G.
      • Mocelin A.O.
      • Camargo P.R.
      • Bocchi E.A.
      Cardiopulmonary exercise testing in children with heart failure secondary to idiopathic dilated cardiomyopathy.

      Class I
      • 1.
        Pre-participation health screening and risk stratification should be performed before initiating a program of exercise training to identify children at risk for adverse events during exercise. Level of Evidence C
      • 2.
        Pediatric patients with HF should undergo cardiopulmonary exercise testing (age ≥ 6–8 years) before initiating exercise training to determine exercise capacity, assess risk for adverse events, and determine suitability for exercise training. Level of Evidence C
      • 3.
        If deemed safe, exercise training in a supervised setting should be prescribed as an adjunctive approach to improve clinical status in ambulatory patients with current or prior symptoms of HF. Level of Evidence C
      Class IIa
      • 1.
        An exercise-training program should be individualized to the patient’s ability and the patient’s response to exercise, with an emphasis on safety. Recommendations for a supervised exercise program should include the frequency, intensity, time, and type of exercise. Level of Evidence C
      • 2.
        Medical contraindications to an exercise-training program should be assessed. Detection of children at risk for sudden death and appropriate recommendations for a defibrillator as a primary or secondary intervention is essential before initiating an exercise program or increasing the frequency, intensity, or duration of a current program. Level of Evidence C
      • 3.
        Informed consent from parents and/or assent from the child should be obtained at each session for exercise training. Level of Evidence C
      • 4.
        Exercise training for children with HF should be performed by personnel with expertise in pediatric exercise physiology and in a facility with the ability to monitor vital signs and perform cardiopulmonary resuscitation. Level of Evidence C

      Acute HF recommendations

      Chairs: Anne I. Dipchand and Elfriede Pahl

      Initial assessment
      • Macicek S.M.
      • Macias C.G.
      • Jefferies J.L.
      • Kim J.J.
      • Price J.F.
      Acute heart failure syndromes in the pediatric emergency department.
      • McMurray J.J.V.
      • Adamopoulos S.
      • Anker S.D.
      • et al.
      ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC.
      • Grady K.L.
      • Dracup K.
      • Kennedy G.
      • et al.
      Team management of patients with heart failure: a statement for healthcare professionals from The Cardiovascular Nursing Council of the American Heart Association.

      Class I
      • 1.
        The diagnosis of acute HF should be based on signs and symptoms of HF combined with supportive evidence from chest X-ray imaging, ECG, echocardiography, and laboratory evaluations, including BNP. Level of Evidence B
      • 2.
        An assessment should be made of the severity of HF, including degree of congestion and adequacy of perfusion (Table 4). Level of Evidence C
        Table 4Categories of Acute Decompensated Heart Failure
        VariableNo congestionCongestion
        “Warm and dry”“Warm and wet”
        Adequate perfusionOptimal profile: focus on prevention of disease progression and decompensationDiuresis with continuation of standard therapy
        “Cold and dry”“Cold and Wet”
        Critical hypoperfusionLimited further options for therapyDiuresis and redesign of regimen with other standard therapies
      • 3.
        An evaluation for the etiology of HF should be performed, with special attention to identifying reversible causes (e.g., repairable CHD, myocarditis, tachycardia-induced cardiomyopathy, and hypothyroidism). Level of Evidence C

      Monitoring
      • Sivarajan V. Ben
      • Bohn D.
      Monitoring of standard hemodynamic parameters: Heart rate, systemic blood pressure, atrial pressure, pulse oximetry, and end-tidal CO2.

      Class I
      • 1.
        In children hospitalized with acute HF, initial observation in an intensive care unit setting should be considered. Level of Evidence C
      • 2.
        In children hospitalized with acute HF, evaluation and monitoring for arrhythmias with continuous ECG monitoring/telemetry is warranted. Level of Evidence C
      • 3.
        Manual blood pressure determination to validate oscillometric determinations during initial evaluations is warranted in the absence of an intra-arterial catheter. Level of Evidence C
      • 4.
        It is reasonable to transfer patients with severe acute HF to a center with pediatric HF specialists and the expertise and ability to optimize medical therapy, evaluate for heart transplant, and if necessary, provide mechanical support. Level of Evidence C
      Class IIa
      • 1.
        In children with decompensated HF, it is reasonable to place intra-arterial catheters for continuous blood pressure monitoring in an acute care setting. Level of Evidence C
      • 2.
        Central venous catheters should be considered in decompensated HF in an acute care setting to allow for measurement of central venous pressure and/or mixed venous saturations and to administer medications and fluids. Level of Evidence C
      Class III
      • 1.
        Pulmonary artery catheterization in children with acute HF is not recommended for routine use, but may be appropriate in selected patients. Level of Evidence C

      Near-infrared spectroscopy

      Class IIb
      • 1.
        Trends in cerebral or somatic regional oxygen saturation and/or venous oxygen saturation levels may be useful in unstable patients with acute heart failure. Level of Evidence C

      Alternative methods for CO/hemodynamic assessment
      • Taylor K.
      • Manlhiot C.
      • McCrindle B.
      • Grosse-Wortmann L.
      • Holtby H.
      Poor accuracy of noninvasive cardiac output monitoring using bioimpedance cardiography [PhysioFlow(R)] compared to magnetic resonance imaging in pediatric patients.

      Class III
      • 1.
        Alternative methods for CO/hemodynamic assessment in acute HF are not recommended for routine use at this time. Level of Evidence B

      Indications for cardiac catheterization
      • Feltes T.F.
      • Bacha E.
      • Beekman R.H.
      • et al.
      Indications for cardiac catheterization and intervention in pediatric cardiac disease: a scientific statement from the American Heart Association.

      Class I
      • 1.
        Coronary angiography is indicated for patients with acute HF if coronary ischemia is suspected in the setting of other potential abnormalities that cannot be definitely excluded by non-invasive imaging. Level of Evidence C
      • 2.
        Cardiac catheterization is indicated in patients with palliated or repaired CHD who present with acute HF if a non-invasive evaluation fails to establish a definitive diagnosis. Level of Evidence C

      Serial testing

      Class I
      • 1.
        Serial testing to monitor for electrolyte abnormalities, hemoglobin levels, end-organ perfusion, and response to therapy are indicated for patients with acute HF. Level of Evidence C

      Inotropes
      • Elkayam U.
      • Tasissa G.
      • Binanay C.
      • et al.
      Use and impact of inotropes and vasodilator therapy in hospitalized patients with severe heart failure.
      • Hoffman T.M.
      Newer inotropes in pediatric heart failure.
      • Ryerson L.M.
      • Alexander P.M.A.
      • Butt W.W.
      • Shann F.A.
      • Penny D.J.
      • Shekerdemian L.S.
      Rotating inotrope therapy in a pediatric population with decompensated heart failure.

      Table 5 summarizes the inotropic characteristics
      Table 5Inotropes Characteristics
      Inotropeα1β1β2DARHalf-lifeCOHRSBPPCWPMyocardial O2 consumption
      Dobutamine++ + + + ++ + +N/A2–3 min
      Epinephrine+ + + + ++ + + ++ + +N/A2–7 min
      Dopamine+ + ++ + + ++++ + + + +2–20 min
      MilrinoneN/AN/AN/AN/A1-4 hours
      LevosimendanN/AN/AN/AN/A1–1.5 hours
      Expansions for the abbreviations used in Table 5 are provided in Appendix 3.
      Class I
      • 1.
        Intravenous inotropic support may be temporarily used in patients with acute HF presenting as cardiogenic shock with poor systemic and end-organ perfusion. Level of Evidence C
      • 2.
        Vasodilators may be used in pediatric patients with acute HF in the absence of hypotension. Vasodilators may be used in combination with diuretics for symptomatic relief in patients with pulmonary edema. Level of Evidence C
      Class IIa
      • 1.
        Intravenous inotropic support may be temporarily used in patients with acute HF presenting as hypotension with evidence of low CO and compromised end-organ perfusion. Level of Evidence C
      • 2.
        The choice of inotropic agent(s) for a child in acute decompensated HF will depend on clinical presentation. Milrinone and/or dobutamine can be used as first-line rescue therapy, with epinephrine playing a role in the face of refractory hypotension and poor end-organ perfusion. Level of Evidence C
      Class IIb
      • 1.
        Levosimendan may be considered in children with acute decompensated HF unresponsive to traditional inotropic therapy. Level of Evidence C
      Class III
      • 1.
        Use of intravenous inotropic agents in the absence of clinical evidence of hypotension, impaired perfusion, low CO, and/or decreased end-organ perfusion is potentially harmful. Level of Evidence B

      Corticosteroids
      • Lindenfeld J.
      • Albert N.M.
      • Boehmer J.P.
      • et al.
      HFSA 2010 comprehensive heart failure practice guideline.

      Class IIb
      • 1.
        In patients with hemodynamic compromise secondary to HF, consideration may be given to evaluation and treatment of adrenal insufficiency. Level of Evidence C

      Anti-coagulation

      Class IIa
      • 1.
        In patients with severe cardiac dysfunction, prophylactic anti-coagulation may be considered, especially in the acute care setting and in the presence of indwelling intravascular catheters. Level of Evidence C

      Thyroid hormone replacement
      • Portman M.A.
      • Slee A.
      • Olson A.K.
      • et al.
      Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC): a multicenter placebo-controlled randomized trial: age analysis.

      Class IIa
      • 1.
        Evaluation of a critically ill patient’s systemic thyroid homeostasis is reasonable, and if hypothyroidism is identified, thyroid hormone replacement may be considered. Level of Evidence C
      Class IIb
      • 1.
        There is no indication for the routine use of thyroid hormone to treat acute HF in the absence of documented abnormal thyroid function. Level of Evidence C
      • 2.
        Thyroid hormone can be considered for use in the acutely unwell post-cardiac surgery patient. Level of Evidence B

      Immunomodulation
      • Liu C.
      • Chen J.
      • Liu K.
      Immunosuppressive treatment for inflammatory cardiomyopathy: meta-analysis of randomized controlled trials.
      • Chen H.
      • Liu J.
      • Yang M.
      Corticosteroids for viral myocarditis.

      Class IIb
      • 1.
        The evidence in the literature does not support the routine use of corticosteroids in children with myocarditis. Level of Evidence C
      • 2.
        The evidence in the literature does not support the routine use of intravenous immunoglobulin in children with myocarditis. Level of Evidence C

      Ventilation
      • Nadar S.
      • Prasad N.
      • Taylor R.S.
      • Lip G.Y.
      Positive pressure ventilation in the management of acute and chronic cardiac failure: a systematic review and meta-analysis.
      • Macicek S.M.
      • Macias C.G.
      • Jefferies J.L.
      • Kim J.J.
      • Price J.F.
      Acute heart failure syndromes in the pediatric emergency department.

      Class I
      • 1.
        Invasive ventilation should be considered in patients with acute decompensated HF and respiratory compromise in the setting of pulmonary edema and/or low CO. Level of Evidence C
      Class IIa
      • 1.
        Non-invasive ventilation may be considered for the treatment of children with acute HF, pulmonary edema, and significant increased work of breathing as an adjunct to other medical therapies. Level of Evidence C
      Class IIb
      • 1.
        Treatment with non-invasive ventilation might be reasonable in children with symptomatic HF in the absence of pulmonary edema as an adjunctive measure. Level of Evidence C

      Fluid management
      • Lindenfeld J.
      • Albert N.M.
      • Boehmer J.P.
      • et al.
      HFSA 2010 comprehensive heart failure practice guideline.
      • Nohria A.
      • Tsang S.W.
      • Fang J.C.
      • et al.
      Clinical assessment identifies hemodynamic profiles that predict outcomes in patients admitted with heart failure.
      • Testani J.M.
      • Chen J.
      • McCauley B.D.
      • Kimmel S.E.
      • Shannon R.P.
      Potential effects of aggressive decongestion during the treatment of decompensated heart failure on renal function and survival.
      • Chen H.H.
      • Schrier R.W.
      Pathophysiology of volume overload in acute heart failure syndromes.

      Class 1
      • 1.
        An initial and ongoing assessment of fluid status should be performed in all patients admitted to the hospital with acute HF. Level of Evidence C
      • 2.
        Diuretics are the first-line therapy for patients admitted with evidence of fluid overload. Level of Evidence C
      • 3.
        Careful monitoring for side effects of anti-congestive therapies, including renal function, electrolytes, and hypotension, should be performed. Level of Evidence C
      Class IIa
      • 1.
        Fluid restriction is reasonable for patients with acute HF, regardless of serum sodium level. Level of Evidence C
      • 2.
        A low-sodium diet is reasonable for hospitalized patients. Level of Evidence C
      Class III
      • 1.
        Sodium supplementation is not recommended in children with HF. Level of Evidence C

      Nutrition
      • Von Haehling S.
      • Doehner W.
      • Anker S.D.
      Nutrition, metabolism, and the complex pathophysiology of cachexia in chronic heart failure.

      Class I
      • 1.
        A nutritional assessment should be performed on hospitalized patients with HF. Level of Evidence C

      Considerations in the treatment of acute right HF
      • Simon M.A.
      Assessment and treatment of right ventricular failure.

      Class IIa
      • 1.
        It is reasonable to use dobutamine, dopamine, or low-dose epinephrine in the setting of right HF. Level of Evidence C
      • 2.
        It is reasonable to use milrinone as a pulmonary vasodilator in the setting of right HF. Level of Evidence C

      Peri-operative acute HF
      • Hoffman T.M.
      • Wernovsky G.
      • Atz A.M.
      • et al.
      Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease.
      • Hoffman T.M.
      • Wernovsky G.
      • Atz A.M.
      • et al.
      Prophylactic Intravenous Use of Milrinone After Cardiac Operation in Pediatrics (PRIMACORP) study.
      • Kaltman J.R.
      • Andropoulos D.B.
      • Checchia P.A.
      • et al.
      Report of the Pediatric Heart Network and National Heart, Lung, and Blood Institute working group on the perioperative management of congenital heart disease.
      • Jaquiss R.D.
      • Bronicki R.A.
      An overview of mechanical circulatory support in children.

      Class I
      • 1.
        Prompt evaluation and treatment of residual hemodynamically significant lesions should be performed when possible for those with early post-operative HF. Level of Evidence C
      Class IIa
      • 1.
        It is reasonable to use milrinone after cardiac surgery in infants and children to reduce the risk of LCOS. Level of Evidence B
      • 2.
        Mechanical circulatory support (ECMO or VAD) is reasonable to use as a bridge to recovery or transplant for infants and children unable to wean from bypass or with refractory LCOS after cardiac surgery. Level of Evidence C

      Transplantation listing recommendations

      Chairs: Richard Kirk and Robert Gajarski
      Pediatric listing guidance was published in 2007, and the ISHLT is currently updating its guidance, including both pediatric and adult congenital listing criteria.
      • Canter C.E.
      • Shaddy R.E.
      • Bernstein D.
      • et al.
      Indications for heart transplantation in pediatric heart disease: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young; the Councils on Clinical Cardiology, Cardiovascular Nursing, and Cardiovascular Su.
      • Mehra M.R.
      • Kobashigawa J.
      • Starling R.
      • et al.
      Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates--2006.
      Accordingly, there are no listing recommendations in this document.

      Health care delivery recommendations

      Chairs: Richard Kirk and Maryanne Chrisant

      Readiness for discharge
      • Jack B.W.
      • Chetty V.K.
      • Anthony D.
      • et al.
      A reengineered hospital discharge program to decrease rehospitalization: a randomized trial.
      • Clancy C.M.
      Reengineering hospital discharge: a protocol to improve patient safety, reduce costs, and boost patient satisfaction.

      Class I
      • 1.
        Discharge criteria (Table 6), if possible, should be met before hospital discharge. Level of Evidence C
        Table 6Proposed Metrics for Heart Failure
        AppointmentsA. Patients are provided with a calendar of scheduled visits (primary cardiologist, HF clinic, outpatient therapies, etc) before hospital discharge
        B. Calendar is refreshed with visits as cycles come to a close
        C. Non-attendance is documented
        D. Electronic application for e-mail and remote scheduling available
        Program adherence to guidelinesA. HF management protocols are documented
        B. Patient variation from protocols are documented with reasons
        C. Documentation of HF severity and staging.
        Frequency or number of unplanned readmissionsA. HF readmissions and emergency department visits
        B. Non-HF–related hospital admissions and emergency department visits
        Monitoring of biomarkers, end-organ function, etcA. BNP, NT-pro-BNP measurements
        B. General metabolic panel for electrolytes, renal function
        C. Hepatic function
        D. Drug levels (if appropriate)
        Remote monitoringA. Physical parameters (feeding, weight gain)
        B. Pacemaker/ICD interrogation if implanted
        C. Loop or event recorders regarding arrhythmias
        Exercise testingA. Metabolic exercise testing over time
        Performance of activities of daily livingA. Feeding, sleep, daily activity journal
        B. Age-appropriate participation: school attendance, peer activity participation
        C. Meeting age-appropriate developmental milestones
        D. Cognitive development
        GrowthA. Growth percentiles and maintenance over time
        NutritionA. Age-appropriate nutritional plan provided
        B. Tracking intake at home with calorie estimation during visits or remotely
        Home monitoring programC. Home monitoring program availability and structure.
        D. Oversight provided by experienced nurse/nurse practitioner.
        E. Tracking of interventions invoked as result of home surveillance.
        Expansions for the abbreviations used in Table 6 are provided in Appendix 3.
      • 2.
        Discharge planning should address medication regimen, fluid and sodium restriction, recommended activity levels, and establishment of early follow-up. Level of Evidence C

      Home surveillance and monitoring
      • Florea V.G.
      • Anand I.S.
      Clinical trial report: reevaluating telemonitoring in heart failure.
      • Giamouzis G.
      • Mastrogiannis D.
      • Koutrakis K.
      • et al.
      Telemonitoring in chronic heart failure: a systematic review.
      • Ghanayem N.
      • Hoffman G.
      • Mussatto K.
      • et al.
      Home surveillance program prevents interstage mortality after the Norwood procedure.

      Class IIb
      • 1.
        Non-invasive home surveillance and monitoring may have a place in HF management. Level of Evidence C
      Class III
      • 1.
        Invasive home monitoring is not recommended because hospitalization is not reduced in adult trials. Level of Evidence C

      Transition
      • Bell L.E.
      • Sawyer S.M.
      Transition of care to adult services for pediatric solid-organ transplant recipients.
      • LaRosa C.
      • Glah C.
      • Baluarte H.J.
      • Meyers K.E.C.
      Solid-organ transplantation in childhood: transitioning to adult health care.

      Class I
      • 1.
        A formal transition program, beginning several years before transfer of care from the pediatric to the adult team, should be a part of routine HF care. Level of Evidence C

      Palliative care
      • Morell E.
      • Wolfe J.
      • Scheurer M.
      • et al.
      Patterns of care at end of life in children with advanced heart disease.

      Class IIb
      • 1.
        Pediatric palliative care should form part of the multidisciplinary care of all patients with potentially end-stage HF, including patients receiving ECMO, VAD support, and patients listed for transplantation. Level of Evidence C

      Disclosure statement

      The authors thank James K Kirklin for his help and guidance.
      The ISHLT funded the cost of conference calls and publication of the monograph detailing the evidence for these guidelines.
      The relevant author disclosures are detailed below:
      Tabled 1
      NameCompanyType of support
      Dimpna AlbertActelionOther research support
      Scott AuerbachHeartWare
      Charles BerulMedtronicTravel, hotel, or registration fee
      Michael BurchNovartisResearch grant site primary investigator or overall primary investigator
      Katrina FordNovartisConsultant
      Daphne HsuNovartisConsultant
      Yuk LawAlereScientific/Medical Advisory Board Member
      Kimberly LinFriedreich Ataxia ResearchOther research support
      David MoralesBerlin HeartResearch grant site primary investigator or overall primary investigator
      Hans Henrik OdlandSt. Jude MedicalTravel, hotel, or registration fee; Speakers Bureau
      David RosenthalBerlin HeartResearch grant site primary investigator or overall primary investigator
      Jeffrey TowbinNational Institutes of HealthResearch grant site primary investigator or overall primary investigator
      None of the other authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.

      Appendix 1. Contributors

      Dimpna Albert, MD (Vall d’Hebron Hospital, Barcelona, Spain), Mark Alexander (Boston Children’s Hospital, Boston, MA), Rebecca Ameduri, MD (University of Minnesota, Minneapolis, MN), Scott Auerbach, MD (Children’s Hospital Denver, Denver, CO), Louise Bannister, RD (Hospital for Sick Children, University of Toronto, Toronto, ON, Canada), Anna Beattie, MD (Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom), Charles I Berul (Children׳s National Medical Center, Washington, DC), Elizabeth D. Blume, MD (Boston Children’s Hospital, Boston, MA), Robert Boucek, MD (Seattle Children’s Hospital, Seattle, WA), Edward Callus, PhD (IRCCS Policlinico San Donato, Italy), Massimiliano Cantinotti, MD (Fondazione Toscana G. Monasterio, Massa and Piza, Italy), Michael Carboni, MD (Duke University School of Medicine, Durham, NC), Regine Caruthers, PharmD (C.S. Mott Children’s Hospital, Ann Arbor MI), Chesney Castleberry, MD (Cincinnati Children’s Hospital Medical Center, Cincinnati, OH), Mitchell I. Cohen, MD (Phoenix Children׳s Hospital, Phoenix, AZ), Jennifer Conway, MD (University of Alberta, Edmonton, AB, Canada), John Costello, MD (Ann & Robert H Lurie Children’s Hospital, Chicago, IL), Michael Dalinghaus, MD (Sophia Children’s Hospital, Rotterdam, the Netherlands), Lara Danziger-Isakov, MD (Cincinnati Children’s Hospital Medical Center, Cincinnati, OH), Bibhuti Das, MD (University of Texas Southwestern Medical Center, Dallas, TX), Susan Denfield, MD (Texas Children’s Hospital, Houston, TX), Sylvie DiFilippo, MD (University of Lyon, Lyon, France), Ali Dodge-Khatami, MD (University of Hamburg School of Medicine, Hamburg, Germany), Debra Dodd, MD (Vanderbilt University, Nashville, TN), Michele Estabrook, MD (Washington University School of Medicine, St. Louis, MO), Brian Feingold, MD (Children’s Hospital of Pittsburgh, Pittsburgh, PA), Matthew Fenton, MBBS (Great Ormond Street Hospital, London, United Kingdom), Katrina Ford, BPharm (Great Ormond Street Hospital, London, United Kingdom), Mathias Gorenflo, MD (Heidelberg University Medical Center, Heidelberg, Germany), Jeffrey Gossett, MD (Ann & Robert H. Lurie Children’s Hospital, Chicago, IL), Gerald Greil, MD, PhD (King’s College, London, United Kingdom), Jakob Hauser, MD (Pediatric Heart Center, Vienna, Austria), Willem Helbing, MD (Sophia Children’s Hospital, Rotterdam, the Netherlands), Timothy Hoffman, MD (Nationwide Children’s Hospital Heart Center, Columbus, OH), Seth Hollander, MD (Stanford University, Stanford, CA), Daphne Hsu, MD (Montefiore University Medical Center, New York, NY), Tarique Hussain, MD (King’s College, London, United Kingdom), Claire Irving, MD (Freeman Hospital, Newcastle upon Tyne, United Kingdom), Robert D.B. Jaquiss, MD (Duke University Medical Center, Durham, NC), Jan Janousek, MD (Children’s Heart Center, Prague, Czech Republic), Aamir Jeewa, MD (Texas Children’s Hospital, Houston, TX), John Lynn Jeffries, MD (Cincinnati Children’s Hospital Medical Center, Cincinnati, OH), John Johnson, MD (Mayo Clinic, Minneapolis, MN), Kirk Kanter, MD (Emory University School of Medicine, Atlanta, GA), Steven Kindel, MD (The Children׳s Hospital and Medical Center of Omaha, Omaha, NE), Michael Kuhn, MD (Loma Linda University Medical Center, Loma Linda, CA), Jacqueline Lamour, MD (Montefiore University Medical Center, New York, NY), Yuk Law, MD (Seattle Children’s Hospital, Seattle, WA), Kimberly Lin, MD (Children’s Hospital of Philadelphia, Philadelphia, PA), Angela Lorts, MD (Cincinnati Children’s Hospital Medical Center, Cincinnati, OH), William Mahle, MD (Emory University School of Medicine, Atlanta, GA), Mike McMullan, MD (Seattle Children’s Hospital, Seattle, WA), Tomoaki Murakami, MD (Chiba Children’s Hospital, Chiba, Japan), Matthew O’Connor, MD (Arkansas Children’s Hospital, Little Rock, AR), Hans Odland, MD, PhD (Oslo University Hospital HF, Rikshospitalet, Norway), Bennett Pearce, MD (University of Alabama at Birmingham, Birmingham, AL), Gregory Perens, MD (University of California at Los Angeles, Los Angeles, CA), Andreas Petropoulos, MD (Merkezi Hospital, Baku, Azerbaijan), Emilia Quadri, PhD (IRCCS Policlinico San Donato, Italy), Chitra Ravishankar, MD (Children’s Hospital of Philadelphia, Philadelphia, PA), Andrew Redington, MD (Hospital for Sick Children, University of Toronto, Toronto, ON, Canada), Mark Richmond, MD (Columbia University Medical Center, New York, NY), Joseph Rossano, MD (Children’s Hospital of Philadelphia, Philadelphia, PA), Paulo Rusconi, MD (Miller School of Medicine, University of Miami, Miami, FL), Elizabeth V. Saarel (Children׳s Primary Medical Center, Salt Lake City, UT), Janet Scheel, MD (Children’s National Health System, Washington, DC), Kurt Schumacher, MD (University of Michigan, Ann Arbor, MI), John Simpson, MD (Evelina Hospital, London, United Kingdom), Rocky Singh, MD (Columbia University Medical Center, New York, NY), Elizabeth Stephenson (Hospital for Sick Children, University of Toronto, Toronto, ON, Canada), Connie White-Williams, ACNP (University of Alabama at Birmingham, Birmingham, AL), Steve Zangwill, MD (Children’s Hospital of Wisconsin, Milwaukee, WI), and Warren Zuckerman, MD (Columbia University Medical Center, New York, NY).

      Appendix 2 External reviewers

      Lee Benson, MD, pediatric cardiologist (The Hospital for Sick Children, Toronto, ON, Canada); Charles Canter, MD, pediatric cardiologist, (St. Louis Children׳s Hospital, St Louis, MO); Asif Hasan, MD, congenital cardiac surgeon, (Freeman Hospital, Newcastle upon Tyne, United Kingdom); Sharon Hunt, MD, adult cardiologist (Stanford University Medical Center, Stanford, CA); Guy McGowan, MD, adult cardiologist (Freeman Hospital, Newcastle upon Tyne, United Kingdom); John O’Sullivan, MD, pediatric cardiologist (Freeman Hospital, Newcastle upon Tyne, United Kingdom); Lucy Roche, MD, pediatric and adult congenital cardiologist (Toronto General Hospital, Toronto, ON, Canada); and Heather Ross, MD, adult cardiologist (Toronto General Hospital, Toronto, ON, Canada).

      Appendix 3 Abbreviations

      Tabled 1
      2-Dtwo-dimensional
      3-Dthree-dimensional
      Mitral A velocitymitral atrial wave velocity
      ACEangiotensin converting enzyme
      AVCarrhythmogenic ventricular cardiomyopathy
      BiVADbiventricular assist device
      BNPB-type natriuretic peptide
      CHDcongenital heart disease
      CRTcardiac resynchronization therapy
      CTcomputed tomography
      COcardiac output
      DARdopaminergic receptor
      DCMdilated cardiomyopathy
      dP/dtechocardiographic measure of change in pressure over change in time
      DSC2Desmocollin-2
      DSG2Desmoglein-2
      DSPDesmoplakin
      e′early mitral annulus descent velocity
      E velocityearly mitral inflow velocity
      ECGelectrocardiogram
      ECMOextracorporeal membrane oxygenation
      EFejection fraction
      EFEendomyocardial fibroelastosis
      EMBendomyocardial biopsy
      GDMTguideline-determined medical therapy
      HCMhypertrophic cardiomyopathy
      HFheart failure
      HFpEFheart failure with preserved ejection fraction
      HRheart rate
      ICDimplantable cardiac defibrillator
      JUPjunctional plakoglobin
      LCOSlow cardiac output syndrome
      LMNAlamin A/C
      LVleft ventricle
      LVEFleft ventricular ejection fraction
      LVNCleft ventricular non-compaction
      MCSmechanical circulatory support
      MPImyocardial performance index
      MRmagnetic resonance
      MRImagnetic resonance imaging
      N/Anot applicable
      NT-proBNPN-terminal pro-B-type natriuretic peptide
      NYHANew York Heart Association
      PCWPpulmonary capillary wedge pressure
      PKP2plakophillin-2
      PVRpulmonary vascular resistance
      RCMrestrictive cardiomyopathy
      RVright ventricle
      SBPsystolic blood pressure
      SCDsudden cardiac death
      S/D ratioratio of systolic-to-diastolic duration
      SCN5sodium channel, voltage-gated, type V, alpha subunit
      TDItissue Doppler imaging
      TMTM43transmembrane protein 43
      ULNupper limit normal
      VADventricular assist device
      Vo2volume of oxygen consumption

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