Heart Failure in Children: Clinical Aspect and Management

Correspondence and Reprint requests : Dr Anita Saxena, Prof.Department of Cardiology, All India Institute of MedicalSciences, New Delhi-110029, India. Phone: 91-11- 26594861, Fax:91-11-26588641[Received January 15, 2009; Accepted January 15, 2009]

Symposium on Advances in Cardiology - II

Heart Failure in Children: Clinical Aspect andManagement

Vivek Chaturvedi and Anita Saxena

Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India

ABSTRACT

Heart failure (HF) is a complex syndrome, with several definitions, the commonest being “an abnormality of cardiac functionwhereby heart in unable to pump at a rate commensurate with the requirement of the metabolizing tissues, or does so onlyat elevated filling pressures”. In case of children, this requirement includes growth and development. Unlike as seen inadults, HF in children is commonly due to structural heart disease and reversible conditions. Thus the treatment for HF iscommonly required for short term only. The overall outcome with HF is better in children than in adults. While the generalprinciples on management are similar to those in adults, the evidence for the use of drugs in children is less convincing. Itrequires a judicious balance of extrapolation from adult medicine, keeping in mind that children are not small adults. [IndianJ Pediatr 2009; 76(2) : 195-205] E-mail: [email protected]

Key words : Heart failure; Congenital heart disease; Drug therapy

Heart failure (HF) is a complex syndrome, with sinisterimplications once diagnosed, the mystery of which isstill being unraveled despite decades of benchside andclinical research. Several definitions have beenproposed for heart failure1, which again reflects our lessthan complete understanding of this enigma. Acommon definition used is2: ‘HF is a patho-physiological state in which an abnormality of cardiacfunction is responsible for the failure of the heart topump blood at a rate commensurate with therequirements of the metabolizing tissues, or does soonly at elevated filling pressures’. In case of children,this requirement includes growth and development.The current American College of Cardiology (ACC)/American Heart Association (AHA) guidelines defineHF as a ‘complex clinical syndrome that can result fromany structural or functional cardiac disorder thatimpairs the ability of the ventricle to fill with or ejectblood’.3 Our current understanding of HF is that of notjust a case of cardiac dysfunction but that of a multi-organ syndrome which explains the myriad patho-physiological and clinical features that accompany it.While HF in adults has been the subject of voluminousresearch and generation of evidence-base, it has

AbbreviationsACE – Angiotensin converting enzymeADHF – Acute decompensated heart failureALCAPA – Anomalous left coronary artery from

pulmonary arteryAR – Aortic regurgitationAS – Aortic stenosisASD – Atrial septal defectARB – Angiotensin receptor blockerAV – ArteriovenousAVSD – Atrio-ventricular septal defectCAD – Coronary artery diseaseCCP – Chronic constrictive pericarditisCHD – Congenital heart diseaseCHF – Congestive heart failureCOA – Coarctation of aortacTGA – Corrected transposition of great arteriesDCM – Dilated cardiomyopathyHLHS – Hypoplastic left heart syndromeHIV – Human immunodeficiency virusHT – HypertensionIHD – Ischaemic heart diseaseICD – Intra-cardiac defibrillatorIVS – Intact ventricular septumJVP – Jugular venous pressureMV – Mitral valveMR – Mitral regurgitationNSAA – Nonspecific aorto-arteritisPAH – Pulmonary arterial hypertensionPDA – Patent ductus arteriosusPPHN – Persistent pulmonary hypertension of the

newbornPS – Pulmonary stenosis

Indian Journal of Pediatrics, Volume 76—February, 2009 195


196 Indian Journal of Pediatrics, Volume 76—February, 2009

received much less attention in children because ofseveral difficulties.

The patho-physiology and etiologies for heart failurein children are very different from those in adults.Common causes of adult heart failure includingischemia, hypertension and valvular inflammation areless common in children. Infants and children developheart failure more commonly due to volume overloadsecondary to shunt lesions, and obstructive lesions ofthe heart. Less common causes include homeostaticabnormalities and cardiomyocyte dysfunctionsecondary to myocarditis / cardiomyopathies. Palliatedcongenital heart disease (CHD) leading to heart failureis increasingly being recognized.

With the aim of keeping this review focused onclinical aspects and management of heart failure, thepathophysiology of heart failure shall not be discussedin detail. Briefly, the manifestations of heart failure arisedue to mismatch of the circulatory load and the abilityof heart, or its components, to pump it in an adequatefashion. These can be accompanied or followed bycompensatory changes in the regional perfusions andrenal, muscular and endocrine physiology (notableamong changes in virtually every organ). The outcomeof this, manifesting as symptoms, is excess extracellular volume in lungs and periphery and decreasedperfusion of vital organs like kidneys and brain as wellas the muscles.

Causes of Heart Failure in Infants and Children

Children can have diverse causes of heart failuredepending on the age, geographical location, and manyother factors. Hence a descriptive epidemiology of heartfailure in children is not possible. The causes of HF canbe broadly classified into two groups; one due tovolume overload of ventricle with preserved systolicfunction of the ventricle, the common example is heartfailure secondary to a large left to right shunt. Thesecond group consists of pressure overload, persistentarrhythmias, dilated cardiomyopathy and certainsystemic disorders where the contractile function ofventricle is reduced (Table 1).

Table 2 enumerates the likely causes of heart failureby age at presentation. This is important, as the

symptoms and signs of heart failure can be confusingor fairly non-specific in children. The lists are not all-exhaustive and the reader is referred to specializedbooks for complete enumeration of heart failureetiologies.

HF presenting on the first day of life are commonlydue to metabolic abnormalities. Structural diseases thatcause HF in neonates usually do not manifest on 1st dayof life; rather it is the causes of fetal HF like Ebstein’s orabnormal heart rate/rhythm that predominate.

About 90% of all cases of HF in children occur beforethe end of first year of life and reflect the preponderanceof CHD as a cause of HF. In the first week of life,obstructive and duct-dependent lesions can presentwith HF or acute circulatory shock. Development of HFdue to left-to right shunts usually waits the fall inpulmonary vascular resistance at 4-6 weeks, thoughlarge VSD, PDA, AVSD and aorto-pulmonary windowcan cause HF by 2nd week of life. Isolated ASD aremostly asymptomatic in children and if an infant isdiagnosed to have ASD and is in failure, the likelydiagnosis is TAPVC.

The myocardium perse is normal in most CHD andthe heart failure, if not presenting in the first year, isunlikely to develop for the next 10 years unlesscomplicated by infective endocarditis, anemia,infections or arrhythmias. Thus older children (usuallybeyond two years) are likely to have other causes for HFlike acute rheumatic fever with carditis, decompensatedchronic rheumatic heart disease, myocarditis,cardiomyopathies and palliated CHD (post Senningoperation for transposition of great arteries or Fontangroup of surgeries for univentricular hearts).

Epidemiology of Heart failure in Children

Epidemiology of heart failure in children is a difficultscience given the fact that symptoms, etiology,

RF – Rheumatic feverRHD – Rheumatic heart diseaseRCMP – Restrictive cardiomyopathySV – Single ventricleTA – Tricuspid atresiaTAPVC – Total anomalous pulmonary venous

connectionTGA – Transposition of great arteriesTOF – Tetrology of fallotTR – Tricuspid regurgitationVSD – Ventricular septal defect

TABLE 1. Causes of Heart Failure

I Volume overload with preserved systolic ventricularfunctiona) Large left to right shunt: VSD, AVSD, PDAb) Admixture lesions with high PBF: TGA, TAPVC,

Truncusc) Regurgitant lesions: MR, AR (Rheumatic/Congenital)

II Myocyte dysfunction with abnormal ventricularcontractile functiona) Pressure overload: Severe AS, PSb) Muscular dystrophy, DCMc) Inflammatory: Myocarditis, Chaga’s, HIVd) Tachycardiomyopathies secondary to SVTe) Abnormal morphology: single ventricular (pre and

post op)f) Ischemic: ALCAPAg) Others: Sepsis, post CPB, hypocalcaemia etc.

Heart Failure in Children: Clinical Aspect and Management


diagnostic criteria, and outcomes are quiteheterogeneous. In Germany, a hospital based study atUniversity Children’s Hospital at Essen studied theepidemiology of heart failure between 1989 and 1998.Heart failure occurred in 40% of all admissions forCHD and one-third of all admissions for all heartdisease (congenital and acquired, n=1755); if post-operative congestive heart failure was excluded, HFaccounted for a quarter of all CHD admissions.Incidence of HF was 289/1000 heart disease patientsand 20.1/1000 of al pediatric inward admissions. In70%, it occurred in the first year of life. Overall mortalityin children with HF was 14%, more than double whencompared to mortality in all heart disease patients.4 Onelarge database from US found out that the heart failurein children (<18 years of age) was complicated by morefrequent procedures, longer stay, but similar mortality asadults (7.5%). The cause was predominantly congenitalheart disease in infants (<1 year of age) at 83% while itwas present in only 34% in children older than 1year ofage. This study however was based on the findings of alarge financial database that was exhaustive, but hadlimited clinical information available.5

In developed countries, the annual incidence of CHDis about 8 per 1000 (0.8%) of live births, of which one-third to on-half are severe enough to warrant attention.Of these, about half result in CHF; thus due to CHD, theincidence of CHF is about 0.1-0.2% of all live births.6

Ninety percent of all cardiomyopathies in childrenare of the dilated variety, others being hypertrophic andrestrictive type. The reported population incidence ofidiopathic DCM in children is 0.6/100, 000 children7

with recent studies showing 5 year rates of death ortransplantation of 46%.8 More than 50% present withinthe first year of life. Children with myocarditis as a

cause of DCM have a favorable prognosis, with 50-80%showing resolution within 2 years of presentation. Thepopulation based studies on childhood cardio-myopathies systematically excluded cardiomyopathiessecondary to cancer drug therapy. At least in the past,anthracycline toxicity has accounted for 50% ofadmissions due to congestive cardiomyopathy inBoston Children’s Hospital.6

Prevalence of heart failure in palliated or operatedCHD cases is unknown. It has been estimated that 10-20% of operated cases with Mustard/Senning surgeryfor transposition of vessels and those with Fontan-typeof operation have symptoms of heart failure.

Rheumatic fever/rheumatic heart disease is animportant cause of HF in children in developingcountries like India. While the incidence andprevalence of RF/RHD are well documented, there areno data on presentation with HF in this group, thougha significant majority of acute rheumatic carditis andestablished juvenile mitral stenosis will present withfeatures of HF. The true incident of HF in children forIndia is not available but is likely to be enormousconsidering the huge burden of the problem of criticalcongenital heart disease in newborns and rheumaticheart disease in older children.

Clinical features

The clinical features of HF in children vary according tothe cause and the age of the child. The presentation ofHF in fetus is that of hydrops fetalis and fetal wastage.

An important point to remember is that raisedjugular venous pressure, peripheral edema, effusionsand chest crepitations are not seen in neonates and areunlikely in young children as a sign of HF. Chest

TABLE 2. Common Causes of Heart Failure by Age at Presentation

Day 1 of life/fetal 1 to 2 monthsAsphyxia Metabolic VSD PDASystemic AV fistula Arrhythmias AVSD Aorto-pulmonary windowMyocarditis Ebstein’s Transposition and Unobstructed

malposition complexes TAPVCHematological ALCAPA

1st week of life (after Day 1) 2 to 6 months

Critical AS/PS Obstructed Causes at 1-2 Aortic stenosisTAPVC months

HLHS COA COAAdrenal insufficiency HypertensionTGA with IVS Day 1 causes

2nd week of life Older children

Large VSD Large PDA CHD with complications RF/RHD(i.e. endocarditis)

AV Septal defect Persistent Cardiomyopathies Palliated CHD /post-Arteriosus Truncus operative

Unobstructed PS, TR cTGATAPVC Tachycardiomyopathy



crepitations in fact suggest the possibility of underlyingchest infection, which so often accompanies HF inchildren especially in high pulmonary flow situations.

Common clinical features of HF in children are given intable 3. Certain features deserve mention:

• The clinical features of HF in a newborn can befairly non-specific; sometimes the clinical pictureresembles that of septicemia. Thus a high index ofsuspicion is required.

• Unequal upper and lower limb pulses, peripheralbruits or raised/asymmetric blood pressureindicating aortic obstruction (including non-specificaortoarteritis, NSAA) , should always be looked forin a child with unexplained HF at any age.

• An interrupted aortic arch or coarctation of aorta(COA) in neonates can have normal femoralpulsations in presence of patent ductus arteriosus(PDA); when the ductus closes, these babies maypresent with acute shock.

• COA usually does not cause HF after one year ofage, when sufficient collaterals have developed.

• Central cyanosis, even if mild, associated with HFand soft or no murmurs in a newborn, shouldalways be taken seriously (suggests transposition ofgreat arteries with intact septum, obstructed totalanomalous pulmonary venous connection etc)

• An ASD or VSD does not cause HF in first 2 weeksof life; their presence with HF should promptevaluation for associated TAPVC or COArespectively.

• A premature newborn with significant respiratorydistress and a systolic murmur should be evaluatedfor patent ductus arteriosus causing HF.

• Heart rates above 220/mt are unusual in a neonateeven with HF and should always be investigated torule out tachyarrhythmias as a cause of HF

• Several children with CHD or cardiomyopathieshave associated chromosomal anomalies or extra-cardiac manifestations which provide clues fordiagnosis.

• Older children with TOF physiology can have HFdue to complicated course (anemia, infectiveendocarditis, bicuspid aortic valve with aorticregurgitation) or overshunting from aorto-pulmonary shunts.

Investigations

The cornerstones for rapid clinical diagnosis of HF inchildren are chest radiograph and anelectrocardiogram.

Chest radiograph: Should be done in all patients withsuspected HF; an echocardiogram is not a substitute for

TABLE 3. Clinical Features of Heart Failure by Age and Associated Findings

Newborn/Neonates

Tachypnea Hepatomegaly Tachycardia Cardiomegaly Bounding pulses in AV malformations, PDA, TruncusFeeding difficulties Excessive sweating Asymmetric upper and lower limb blood pressure in aortic arch

anomaliesSubcostal recession Cyanosis and wheeze Central cyanosis in TGA, TAPVC, Truncus , TA with no PS

Differential cyanosis in PPHN and R-L shunt through patent ductusMultiple heart sounds in Ebstein’sEjection systolic murmur in AS/PSSyndromic anomalies (Down’s, Noonan)

Shock Think of HLHS, COA, Interrupted aortic arch, critical AS,tachyarrhythmias, myocarditis

Infants

Poor feeding Lethargy Precordial bulge, signs of PAH and less impressive systolic murmurssuggest larger L-R shunts

Excessive sweating Tachypnea, tachycardia Crepitations should alert to possibility of chest infectionSlow weight gain Hepatomegaly Cyanosis in TAPVC, TGA with VSD, AVSD, Truncus

Findings of CHF and cyanosis in suspected ASD suggest TAPVCLater onset of HF in infancy can be due to certain forms of TAPVCand ALCAPA

Older children

Poor weight gain Effort intolerance, orthopnea Diastolic murmur in a child with known VSD suggestsassociated AR

Cardiomegaly Gallop rhythm, murmurs Pericardial rub in appropriate settings suggests acute RFPeripheral edema Basilar crepitations Hypertension and unequal pulses or bruits suggest NSAAFatigue Hepatomegaly Findings of raised JVP, ascites and anasarca should lead toRaised JVP suspicion of CCP or RCMP



radiograph. It enables diagnosis of cardiomegaly,quantification of pulmonary blood flow, presence ofassociated chest infection, pleural effusion etc., as wellas being pathognomonic in certain disease states. Acardiothoracic ratio of >60% in neonates and >55% inolder children suggest cardiomegaly though expiratoryfilms should be interpreted with caution. A largethymus can also give false impression of cardiomegalyin neonates and infants (Fig. 1). Cardiomegaly withincreased pulmonary blood flow (pulmonary plethora),prominent main and branch pulmonary arteries, leftatrial enlargement etc. are signs of significantlyincreased pulmonary blood flow (a finding notappreciable on echocardiogram!) which could causeHF (Fig. 2). Typical radiographs strongly suggestive ofcertain diagnosis include those with transposition ofgreat arteries (egg-on-side, Fig. 3), obstructed TAPVC(snowstorm appearance, Figure 4), unobstructedTAPVC (Fig. of 8 appearance, Fig. 5), Truncus arteriosus(waterfall appearance of hila, Fig. 6), Ebstein’s anomaly(globular cardiomegaly with decreased pulmonaryflow), CCP (calcification in RV/AV groove), juvenilemitral stenosis (left atrial appendage enlargement), etc.

Electrocardiogram: An electrocardiogram is very usefulin heart failure for elucidation of cardiac diagnosis. Itshows biventricular hypertrophy with volume overloadof the left ventricle in the commonest cause of HF in theinfant i.e. a large VSD. Tachycardiomyopathy, a

Fig. 2. Chest radiograph showing cardiomegaly, prominentpulmonary artery segment and increased pulmonaryblood flow in a case of large VSD.

Fig. 1. X-ray chest of a normal neonate with a large thymus.

Fig. 3. Chest radiograph of a newborn with transposition ofgreat arteries (egg-on-side)

Fig. 4. Chest radiograph of a newborn with obstructed TAPVCshowing the ‘snow-storm’ appearance

Fig. 5. Chest radiograph in an older child with uobstructedTAPVC showing the typical ‘figure of 8’ appearance ofmediastinum.



potentially reversible cause of HF, due to incessantsupraventricular tachycardias (like ectopic atrialtachycardia) can only be picked up by ECG (Fig. 7).Similarly bradyarrhythmias due to congenital completeheart block are detected on ECG (Fig. 8). Certainpatterns on ECG are also virtually diagnostic of specific

Fig. 7. Electrocardiogram of a child presenting with heart failuredue to atrioventricular re-entrant tachycardia at the rateof 200 beats per minute. Arrows point to P waves. Notethat RP interval is shorter than PR interval.

Fig. 8. Holter trace of an infant with bradycardia (ventricularrate of 40 beats per minute) due to congenital completeheart block. Note that there is no relationship between Pwaves and QRS complexes.

Fig. 9. Electrocardiogram of a child with ALCAPA showingpresence of pathologic q waves and ST – T changes(arrows) in lateral leads.

Fig. 10. Electrocardiogram of a child with atrioventricular septaldefect showing left axis deviation and right ventricularhypertrophy.

Fig. 11. Electrocardiogram from a child with hypocalcemiashowing long QTc interval and bizarre, inverted Twaves (white arrow).

Fig. 6. Chest radiograph in an infant with persistent truncusarteriosus.

cardiac pathologies. Thus ALCAPA can present withpathognomonic pathologic q waves in anterolateralleads (Fig. 9). A superior or northwest axis with BVHsuggests atrioventrcular septal defect as a cause of HF(Fig. 10). In a neonate with unexplained HF, aprolonged QTc interval with terminal T wave inversion



are suggestive of hypocalcemia as the cause of leftventricular dysfunction (Fig. 11).

Echocardiogram: An echocardiogram is invaluable inthe diagnosis of heart failure. It confirms the presenceof structural heart disease and great vessel anomaliesand aids in the acute and long term managementstrategy. While an echocardiogram is essential fordiagnosis of heart disease in HF, as mentioned above, itshould always be interpreted in an integrated fashionwith clinical, radiographic and ECG findings. Owing toits dependence on operator skills and inherentproblems of imaging small children, an echo can missfindings such as TAPVC and aortic arch anomalies.However echo by a skilled echocardiographer isadequate for diagnosis and initial management ofpractically all diseases causing HF.

Other investigations

B-type natriuretic peptide (BNP): BNP, a cardiacnatriuretic hormone, secreted in escalating fashion inventricular dysfunction and progressive HF, isincreasingly used in acute settings for differentiation ofHF from pulmonary causes of respiratory distress.While its utility in adults is established, its incrementalvalue in pediatric patients is still investigational.Plasma BNP elevation is a reliable test however forrecognizing ventricular dysfunction in children with avariety of CHD.9

Hemoglobin is important in diagnosis of HF inchildren; while protracted values around 5 gm/dl cancause HF even with a normal heart, hemoglobin of 7-8gm/dl can cause decompensation in cases withunderlying heart disease but no HF. Electrolytes likeserum calcium, phosphorous and blood glucose shouldbe routinely measured in all children with HF,especially neonates, where their abnormalities are anuncommon but reversible cause of ventriculardysfunction. Similarly screening for hypoxia and sepsisalso constitute evaluation of HF in a newborn. Work-upfor ascertainment of etiology of myocarditis andcardiomyopathy is exhaustive and detailed elsewhere10.ASO (anti-streptolysin O) and CRP (C-reactive protein)are invaluable in work up for diagnosis of suspectedprimary attack of rheumatic fever (RF) or recurrence ofRF in cases with rheumatic heart disease.

Staging the severity of Heart Failure

While several systems exist for grading severity of HF inadults, including universally known New York HeartAssociation Class, it is difficult to grade HF or applythese classifications in children especially infants. Acommon system followed is that advocated by Ross11 forclassification of heart failure (Table 4) and scoring itsseverity (not shown).

Management of Heart Failure

The management of HF in children can be divided intofollowing categories:

1. CHD presenting with acute shock, whereimmediate treatment (pharmacologic, percutaneous,or surgical) is required

In neonatal period several causes of HF can presentwith acute circulatory collapse or progress to shock ifnot recognized early. These can be due to

• A closing ductus where antegrade systemic flow iscompromised, for e.g., tight COA, interruption ofaortic arch, critical AS, HLHS, and TGA with intactseptum and restrictive inter-atrial communication.These disorders require maintenance of ductpatency with prostaglandin infusion till the timemore definitive treatment can be employed. Thisconsists of percutaneous procedures for critical AS(valvuloplasty), TGA (balloon atrial septostomy) aswell as surgical procedures for neonatal COA,HLHS etc. In cases where surgery for COA is notpossible due to severe comorbid conditions, aballoon dilatation is performed, although therestenosis rates are likely to be higher.

• Conditions like mitral atresia (requiring emergencyatrial septostomy) and obstructed TAPVC (requiresemergency surgery) can cause severe elevations inpulmonary venous pressure and have similarconsequences.

• Non-cardiac cause of neonatal HF, tachyarrhy-thmias and neonatal myocarditis can also rapidlyprogress to shock if not managed early.

• Lesions like AS, PS and COA, if associated withcorresponding ventricular dysfunction or heartfailure should undergo urgent relief of obstruction,irrespective of magnitude of gradient at baseline.

Because these children are very sick, they should betransferred to tertiary centers with expertise in theircare, after initial resuscitation and prostaglandininfusion (if required). They require intensive monitoringbecause of frequent co-morbidities and likely

TABLE 4. Ross Classification of Heart Failure in Infants

Class I No limitations or symptomsClass II Mild tachypnea or diaphoresis with feeding in infants Dyspnea on exertion in older children No growth failureClass III Marked tachypnea or diaphoresis with feeds or

exertion Prolonged feeding times Growth failure from CHFClass IV Symptoms at rest with tachypnea, retractions,

grunting, or diaphoresis



requirement of ventilation (due to pulmonary edema,chest infections or due to apnea as an adverse effect ofprostaglandin therapy)

2. CHD awaiting surgery where medical treatment isapplied for stabilization and alleviation ofsymptoms- short-term medical therapy

This is a very common group because except someVSDs and PDA in premature babies (which may closespontaneously), most of CHDs causing HF requiresurgical intervention. These children present with HFand frequently have co-morbidities like sepsis or chestinfection. They tolerate repeated bouts of HF and chestinfection (which enters into a vicious cycle with HF)poorly and should undergo surgery or nonsurgicalcatheter intervention promptly after stabilization ofmedical condition12. These conditions include

• Large VSD/PDA/AVSD/Persistent truncusarteriosus with uncontrolled CHF or history of lifethreatening infection

• Severe AS or COA

• TGA with IVS and prepared LV

• Unobstructed TAPVC.

3. CHD requiring long term medical therapy

Several causes of HF in children require prolongedmedical therapy because of tendency for spontaneousresolution or a cure for the condition in long term or dueto the fact that the surgical treatment is problematic.

• Ventricular septal defect is one of the commonestcauses for HF after the neonatal period, in infancy.About 10% of non-restrictive VSD die in 1st year oflife, primarily due to CHF. However up to 30-40% ofsmall or moderate sized defects close spontaneously(mostly by 3-5 years of age) and 25% decrease insize13. A minority of VSD with large L-R flow canalso close spontaneously14. Thus at least some VSDpresenting in infancy with less than severe HF canbe judiciously followed on medical therapy andwatched for spontaneous closure. Similarly, smallPDAs in term babies uptil 3 months of age, and thosein premature babies not in HF (with or without theuse of indomethacin) may be observed forspontaneous closure.

• Myocarditis in children is a potentially reversiblecause of HF provided the acute phase is cared forwith the best available medical care (ventricularassist devices, if necessary). Similarly someuncommon causes of cardiomyopathies (e.g.carnitine deficiency associated) can be treatedeffectively with supplementation.

• Some conditions like congenital mitral stenosis areproblematic to manage in infancy and it is prudent todefer surgery till later if the child is growing

normally.

4. Long-term therapy in cases with irreversiblemyocardial dysfunction or where no other definitivetherapy can be offered.

Finally, there is the group of conditions causing HFwhere there is established myocardial dysfunction. Thiscan be due to cardiomyopathies (primary andsecondary), decompensated systemic ventricle (SVphysiology, cTGA), and following palliative surgeries.This group displays the whole spectrum fromasymptomatic ventricular dysfunction to decompensatedHF and requires long term medical therapy. HF therapyis also required long term in residual defects followingsurgery and in valvular diseases where the risk-benefitratio is not in favour of surgery.

Drugs for Treatment of Heart Failure

Management of CHF in children is complex because offrequent presence of structural heart disease (on whichmedical treatment has little effect) and variablepresentation and spontaneous resolution of somediseases. On the other hand, advances in medicalscience have ensured a wide variety of evidence-basedand emerging therapies for treatment or palliation ofHF (Table 5). There are several newer agents, the rolesof which are still investigational, in adults and inchildren. These include natriuretic peptides (e.g.,nesiritide), calcium sensitizers (e.g., levosimendan),vasopressin antagonists (e.g., tolvaptan), renininhibitors (e.g., aliskiren), endothelin antagonists (e.g.,sitoxentan) etc. Some like oral phosphodiesteraseinhibitors, anti-inflammatory molecules, nitric oxideagonists, and neuropeptidase antagonists have notproven useful or found to have excess side-effects.

Most of this evidence base has been generated inadults in whom randomized trials usually happenTABLE 5. Treatment Options for Chronic Heart Failure

Established InvestigationalPharmacotherapy

ACE Inhibitors Angiotensin receptor blockerBeta-blockers NesiritideDigoxin LevosimendanDiureticsAldosterone antagonistsAnticoagulants (withsevere ventriculardysfunction)

Cardiac transplantationSurgeryDefinite Ventricular remodeling(for structural disease)Ventricular assist devices Cardiac resynchronization

therapyExtracorporeal membrane ICDoxygenationIntermittent ionotrope infusion Stem cell therapy(weekend pulsed dobutamine)



earlier. Conducting such trials in children has beendifficult on account of ethical issues and logisticalproblems. While treatment of HF in children is oftenextrapolated from that in adults, this may not be accurateowing to different pathophysiology and etiology of HF inchildren. These dilemmas are exemplified by the recentlypublished randomized controlled trial for carvedilol inchildren15 with HF, where beta-blockade did not improveoutcomes over those with placebo. While smalleruncontrolled studies earlier had shown significantbenefit with carvedilol, the neutral results of this trialwere presumably due to inadequate sample size (due tohigh rate of spontaneous improvement in placebo group)and heterogeneous effect of drug on type of systemicventricle (beneficial in systemic left ventricle only). Tables6-8 outline the treatment of heart failure in children anddosages of common drugs used for treatment in acuteand chronic settings.

children and adults alike. It should be avoided inpremature babies, those with renal compromisedstate and cases with acute myocarditis. Electrolytes(K+, Ca++, Mg++) should be carefully monitored toavoid potentiation of toxicity and development ofarrhythmias (which are more oftenbradyarrhythmias in children)

• Generally initial total digitalization is notperformed. One can start directly to oralmaintenance dose at 10 mcg/kg/day (Theavailable digoxin elixir has 50 mcg/ml, hence thedose is 0.1 ml/kg twice daily)

• Continuous infusion of diuretics is recommendedin cases of acute decompensated heart failure(ADHF). Monitoring and supplementation of K+ isnecessary at higher doses, as deficiency isassociated with increased arrhythmic death.

• During early infancy supplementation ofpotassium is usually not required uptil 2mg/kg ofdose for furosemide or equivalent. In these cases we

TABLE 6. Treatment Algorithm for Acute Heart Failure inNeonates

Supportive measuresAvoid hypothermia and hypoglycemia, check for hypocalcemia

Maintenance of Monitoring of blood gases if perfusionadequate oxygenation is poor Ventilate, if required, with

modest PEEP to achieve PaO2 of 50-60 mmHg and SaO2 of 75-85% toavoid pulmonary congestion

Adequate hydration Stop oral feeds if severe tachypneaIntravenous access I/V and CVP lines (umblical vein

cannula)Intravenous ionotropes Isoproterenol 0.5-2 mcg/kg/minfor shock Dopamine 5-20 mcg/kg/min

Dobutamine 5-20 mcg/kg/minAvoid digoxin or use cautiously

Milrinone Ionotrope and vasodilatorLoad with 25-50 mcg/kg/min.maintain at 0.25-1 mcg/kg/min

Diuretics Furosemide 2-4 mcg/kg PO/IVVasodilators Captopril 0.1-1 mg/kg/day PO q 8hrly

Sodium nitroprusside 0.5-4 mcg/kg/min IVCareful monitoring of blood pressurenecessary

Prostaglandin infusion Start at 0.1 mcg/kg/min (uptil 0.4for ductus-dependent mcg/kg/min if no response), taper tolesions lowest dose possible (0.005 mcg/kg/

min) Monitor for apnea, keep minimumrequired dose

Management of Heart Failure: Important Issues inchildren

• Treatment of HF in children, like in adults, shouldconsist of treatment of the cause, precipitatingfactors (like anemia, infective endocarditis,infections, acute rheumatic fever, non-compliancewith drug or diet, arrhythmias, etc), and treatmentof the congested state.

• Digoxin has a very narrow safety window in

TABLE 8. Stepwise Guide to Management of Heart Failure

Step 1 In acute decompensation : bed rest, propped upposition, humidified oxygen Sodium and, if required,volume restriction.

Step 2 Start digoxin (not in myocarditis)Assess reversible causes and precipitating causesAssess the need for surgery/ interventionalprocedure in case of structural heart disease

Step 3 Add ACE Inhibitor. In case of ACEI induced cough,switch to ARB like losartanSwitch to nitrates if ACE Inhibitor/ARB nottolerated

Step 4 Add carvedilol in compensated HF especially incases with tachycardia

Step 5 Once or twice weekly dobutamine therapyConsider stem cell coronary infusion

Step 6 Cardiac transplantationVentricular assist device as bridge in case of delaysor even ?destination

TABLE 7. Oral Dosages of Common Drugs Used to TreatChronic Heart Failure

Digoxin 10mcg/kg/day (in two divided doses forchildren <5 years)

Furosemide 1-4 mg/kg/day (1-2 doses)Spironolactone 2-4 mg/kg/day (2 doses)Captopril Neonates: (0.4-1.6 mg/kg/day) in 3 divided

dosesInfants and children : 0.5-4 mg/kg/day in 3divided doses

Enalapril 0.1-0.5 mg/kg/day (2 doses)- avoid inneonatesLosartan 0.5 mg/kg/day once dailyMetoprolol 0.1-0.2 mg/kg/dose (2 doses) and increase to

1 mg/kg/dose or maximally tolerated doseover weeks or months

Carvedilol 0.05 mg/kg/dose (twice daily) and increase to0.4-0.5 mg/kg/dose (twice daily) ormaximally tolerated dose



give the parentral preparation of furosemide orallyfor logistic reasons as furosemide syrup is notavailable in our country. In other cases requiringhigher doses and in older children, we usually givea combination of loop diuretic and spironolactone(or other potassium sparing diuretics). In casesrequiring chronic therapy, development of diureticresistance is quite common. Addition of low dosedopamine may help in this situation by increasingrenal blood flow.

• ACE Inhibitors should be avoided in HF caused bylesions having pressure overload physiology e.g. inaortic stenosis, as they might interfere withcompensatory hypertrophy. The incidence of ACEInhibitor induced cough is much less in childrenas compared to adults.

• Beta blockers should not be administered in acutedecompensated heart failure. They should bestarted once child is stable at low dose, and slowup-titrations (once every two weeks through 4levels according to pediatric carvedilol studygroup trial15) should be done as this determines theoccurrence and degree of side effects. In case up-titration is not tolerated, lower doses should becontinued rather than discontinuing the drug. Inthe carvedilol trial, overall about 20% children hadworsening of HF in both carvedilol and placebopopulation, of which 11% each withdrew from thestudy due to this.

• Persistently high heart rates (>180/min in olderchildren) with absence of normal variability duringsleep or exercise should always be investigated torule out tachycardiomyopathy as the cause of HF.

Myocarditis/Cardiomyopathy

Acute myocarditis and pediatric cardiomyopathydeserve a special mention as despite intensive researchthey still are an enigma and a challenge to clinicians.Many clinicians view acute myocarditis andcardiomyopathy in children as a continuum; indeed alarge study in North America found myocarditis as themost common cause of cardiomyopathy (46%)8. Thishowever increases the ambiguities in the diagnosis ofmyocarditis especially the relevance and indications oftissue diagnosis by endomyocardial biopsy. Severalsmall studies have been conducted withimmunoglobulin and immunosuppressive therapy inchildren with acute myocarditis. However robust trialsare few, with the outcome that there is still noconsensus on use of these therapies16, 17. Of note, studiesin myocarditis indicate a high prevalence of resolutionof cardiomyopathy in 2 years to the tune of 50-80%18.Children with fulminant myocarditis with a highchance of recovery, do well when put on extracorporealmembrane oxygenation (ECMO) and ventricular assist

devices 19, 20. These findings suggest that a diagnosis ofmyocarditis is a positive prognostic factor in childrenwith HF even if requiring mechanical support.Therefore circulatory assist devices, if available, shouldbe used aggressively in these children.

Cardiac transplantation

Heart transplantation has been used for treatment ofend-stage heart disease in children for nearly 4 decadeswith first infant transplant done in late 1960s. Around350 pediatric cardiac transplantations are doneannually, representing about 10% of total cardiactransplantations. Majority of the transplantations arecarried out for end-stage heart disease due tocardiomyopathies. Other causes include congenitalheart diseases like hypoplastic heart syndrome andother complex CHD, single ventricle, palliated heartdisease, etc. One year survival has approached 90% andestimated conditional graft half-life is about 17.5 yeasin younger children (in comparison immediate waitinglist mortality is about 20 %.)18. However, given the factthat the surgery is done in few centers globally and theavailable donor hearts have remained static over lastmany years to few hundreds, it is clear that hearttransplantation can be a solution for a minority only.

Stem Cell Therapy

A heightened interest has developed in stem celltherapy for heart failure. Several trials have beencompleted, or are ongoing in adults with HF,predominantly due to ischemic heart disease. Stem celltherapy has been also used for non ischemiccardiomyopathy at our center21, and is beinginvestigated worldwide under experimental settings,including our center, for children with refractory heartfailure who are not candidates for transplantation.

CONCLUSION

HF in children is a complex syndrome withheterogeneous etiology and presentation. Unlike adults,HF in children is commonly due to structural heartdisease and reversible conditions, thus lending itamenable to definitive therapy or short term aggressivetherapy. Thus the overall outcome with HF is better inchildren than that in adults. Clinical presentation of HFin younger children can be non-specific requiringheightened degree of suspicion. In particular, someconditions that can present with acute shock areimportant to recognize, as they can be effectively treatedor palliated on an urgent basis. While the generalprinciples of management are similar to those in adults,there is a dearth of evidence base in pediatric heartfailure. It would require a judicious balance ofextrapolation from adult medicine (thus avoiding



generation of redundant evidence) and development ofchildren specific treatments ( thus recognizing theinherent differences in HF of children and adults) tooptimize the outcomes in this challenging field.

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Heart Failure in Children: Clinical Aspect and Management

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