Hypertrophic cardiomyopathy in children: Management and prognosis

INTRODUCTION — Hypertrophic cardiomyopathy (HCM) is one of the most common forms of inherited cardiomyopathy in both adults and children. It is characterized by hypertrophy of the left ventricle (image 1A-B and image 2A-B). The disease course is highly variable, but it is well recognized that there is an increased risk of cardiac morbidity, including sudden cardiac death (SCD).

This topic will review the management and prognosis of HCM in children. The clinical manifestations and diagnosis of pediatric HCM and other related topics are discussed separately:

●(See "Hypertrophic cardiomyopathy in children: Clinical manifestations and diagnosis".)

●(See "Sudden cardiac arrest (SCA) and sudden cardiac death (SCD) in children".)

●(See "Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and evaluation".)

●(See "Hypertrophic cardiomyopathy: Natural history and prognosis".)

●(See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".)

●(See "Hypertrophic cardiomyopathy: Management of patients without outflow tract obstruction".)

●(See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction".)

DEFINITIONS — The terms HCM and left ventricular hypertrophy (LVH) are applied broadly to a number of different clinical presentations:

●Genetically determined HCM – Genetically determined HCM includes sarcomeric and nonsarcomeric (or syndromic) HCM; the term specifically excludes LVH due to secondary influences (eg, athletic training, hypertension, other systemic illnesses).

•Sarcomeric HCM – Sarcomeric HCM (sometimes referred to as "true HCM") is a condition caused by pathologic variants in genes encoding sarcomeric proteins (figure 1). (See "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing", section on 'Sarcomeric gene mutations causing HCM'.)

•Nonsarcomeric (or syndromic) HCM – Increasingly, variants in nonsarcomeric genes encoding proteins with a wide range of functions have been shown to cause HCM [1]. There are a number of genetic syndromes and neuromuscular disorders that present with morphologic characteristics similar to sarcomeric HCM (sometimes called "HCM phenocopies" or "syndromic HCM") [2]. These include inborn errors of metabolism, multiple congenital anomaly syndromes (eg, Noonan syndrome), mitochondrial disorders, and neuromuscular disorders (table 1). The most common of these syndromes is Noonan syndrome, with other examples including Danon disease, Friedreich ataxia, Fabry disease, LEOPARD syndrome, Pompe disease, and mitochondrial diseases [3]. Mutations of PRKGA2 are another rare cause of nonsarcomeric HCM. (See "Hypertrophic cardiomyopathy in children: Clinical manifestations and diagnosis", section on 'Genetics' and "Hypertrophic cardiomyopathy: Gene mutations and clinical genetic testing", section on 'Nonsarcomeric causes of LV hypertrophy'.)

There is debate over whether syndromic causes of HCM should be included when describing pediatric HCM. The approach to therapy is often the same, though it is worth noting that patients with syndromic causes of HCM are often excluded from studies of medical and implantable cardioverter-defibrillator (ICD) therapy. In addition, the prognosis is generally worse for syndromic HCM, as discussed below. (See 'Prognosis' below.)

In this topic review, nonsyndromic and syndromic causes of HCM are considered together under the broad term "HCM," unless otherwise specified.

•Obstructive versus nonobstructive HCM – Patients with HCM who have significant left ventricular outflow tract (LVOT) obstruction (ie, gradient ≥50 mmHg) are classified as having obstructive HCM, whereas those with mild or no LVOT obstruction are classified as having nonobstructive HCM. The management approach for patients with obstructive HCM differs from that of nonobstructive HCM, as discussed below. (See 'Patients with obstruction' below and 'Patients without obstruction' below.)

•Preclinical HCM – The term preclinical HCM (also called genotype-positive/phenotype-negative [G+ P-]) describes individuals who are known to carry a pathologic variant in a gene associated with HCM but who lack current clinical evidence of HCM (ie, no LVH on echocardiography). G+ P- individuals are typically identified through cascade testing after a family member is diagnosed with HCM. (See "Hypertrophic cardiomyopathy in children: Clinical manifestations and diagnosis", section on 'Evaluation of first-degree relatives'.)

●Adaptive or secondary LVH – Adaptive changes to stimuli such as athletic training or hypertension can occur in pediatric patients; however, LVH resulting from these adaptations is not considered HCM. In addition, secondary causes of LVH such as pulmonary parenchymal or vascular disease, endocrine disease (eg, maternal diabetes), rheumatic disease, immunologic disease, and cardiotoxic exposures are not considered HCM. (See "Hypertrophic cardiomyopathy in children: Clinical manifestations and diagnosis", section on 'Differential diagnosis'.)

GENERAL MEASURES

Treatment goals — The goals of management in patients with HCM are to reduce symptoms, preserve LV function, and prolong survival [4].

Therapies to avoid — Therapies to avoid in patients with HCM who have evidence of LV outflow tract (LVOT) obstruction include:

●Avoidance of volume depletion – In patients with obstructive HCM, volume depletion tends to decrease stroke volume and worsen the LVOT gradient (or induce an LVOT gradient if no gradient is present during euvolemia). Worsening of the LVOT gradient, particularly when volume-depleted, can lead to hypotension, lightheadedness, and syncope. For those with symptomatic nonobstructive HCM, cardiac output is reliant on preload, and volume depletion can lead to low cardiac output.

●Avoidance of medications that may increase the LVOT gradient – Medications that can increase the LVOT gradient should be avoided, including:

•Vasodilators – Vasodilators, such as angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, dihydropyridine calcium channel blockers (eg, nifedipine, amlodipine), and nitroglycerin can produce a decrease in peripheral resistance with an increase in LVOT obstruction and filling pressures, thereby resulting in hypotension and/or worsening heart failure (HF) symptoms [4].

•Diuretics – By reducing preload, diuretics can result in less LV filling and a smaller LV chamber, and, therefore, greater outflow obstruction. However, cautious use of diuretics may be attempted only in nonobstructed HCM patients with persistent HF and evidence of volume overload.

•Digoxin – Digoxin is generally avoided in HCM given that LV function is hyperdynamic at baseline. One exception is in patients with systolic dysfunction, as seen in "burned-out" HCM. In this case, standard HF therapies, including digoxin, may be indicated. (See "Heart failure in children: Management", section on 'Digoxin'.)

Management of other cardiovascular risk factors — Every effort should be taken to address modifiable risk factors that can cause or contribute to LVH or increased myocardial stress [2]. These include:

●Hypertension (see "Nonemergent treatment of hypertension in children and adolescents")

●Obesity (see "Prevention and management of childhood obesity in the primary care setting")

●Sleep-disordered breathing (see "Management of obstructive sleep apnea in children")

These comorbidities may increase disease penetrance in genotype-positive individuals (hypertension), worsen symptoms or exacerbate arrhythmias in patients with extant HCM (sleep-disordered breathing, obesity), and may be associated with increased risk of adverse outcomes such as HF, atrial fibrillation, stroke, ventricular arrhythmias, and death.

INITIAL MANAGEMENT APPROACH — The initial management of pediatric patients with HCM depends on the patient's symptoms and whether there is LV outflow tract (LVOT) obstruction.

Patients with obstruction

Asymptomatic patients — Management of asymptomatic patients with LVOT obstruction varies considerably and the optimal approach is uncertain. In our practice, we generally initiate pharmacologic therapy (usually with a beta blocker) if the LVOT gradient is moderate or higher (ie, ≥50 mmHg at rest). Part of the rationale for treating patients with a moderate or high LVOT gradient even in the absence of apparent symptoms is that some pediatric patients, particularly young children, may not reliably report symptoms. Thus, it is difficult to establish whether the patient is truly asymptomatic. However, other experts do not treat asymptomatic patients regardless of the LVOT gradient.

When the decision is made to start treatment in an asymptomatic patient, we generally start with a beta blocker. A nondihydropyridine calcium channel blocker (eg, verapamil) is another reasonable option. (See 'Initial therapy (beta blockers)' below and 'Second-line therapies' below.)

Data to guide this decision are limited [5]. The practice of using beta blockers and calcium channel blockers in this setting is supported by clinical experience and indirect evidence from small studies (mostly involving adult patients with symptomatic LVOT obstruction) demonstrating improvements in the LVOT gradient and exercise performance. These data are discussed separately. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Initial medical therapy for symptomatic patients'.)

Symptomatic patients — For patients with clinically significant LVOT obstruction (ie, gradient ≥50 mmHg) with associated symptoms, pharmacologic therapy is used to decrease myocardial oxygen demand and slow the heart rate to improve ventricular filling (ie, keeping the heart "slow and full") in an effort to reduce the effective LVOT gradient. Beta blockers are the most commonly used agents in children.

Initial therapy (beta blockers) — In children with HCM who have an LVOT gradient ≥50 mmHg and symptoms attributable to obstruction, we suggest treatment with a beta blocker rather than other single agents or combination therapy. In children ≥12 months of age, a nondihydropyridine calcium channel blocker (typically verapamil) is a reasonable alternative option for initial therapy.

Our preference for beta blocker therapy is based on our experience and the relative ease of dosing with beta blockers. Data to guide the choice of initial therapy in children with symptomatic HCM are limited [6]. Indirect evidence from small studies in adult patients with symptomatic LVOT obstruction has demonstrated that beta blocker therapy is associated with improvements in the LVOT gradient and exercise performance. These data are discussed separately. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Initial therapy (beta blocker)'.)

Second-line therapies

●Calcium channel blockers – For patients who are intolerant of beta blockers due to side effects, we typically treat with a nondihydropyridine calcium channel blocker monotherapy (usually verapamil) or disopyramide monotherapy. We avoid verapamil in infants <12 months of age due to concerns for apnea, hypotension, and cardiac arrest [7].

●Combination therapy – For patients who have significant symptoms and LVOT obstruction despite a one to three month trial of monotherapy, options for combination therapy include:

•Beta blocker plus nondihydropyridine calcium channel blocker – A beta blocker in combination with verapamil is our preferred combination therapy. However, this approach is frequently limited by symptomatic bradycardia, which is more common in younger patients who are more dependent on calcium and less tolerant of bradycardia. Regardless of which combination is chosen, patients should be monitored for adverse effects, including bradycardia, hypotension, fatigue, decreased appetite, and feeding intolerance.

•Disopyramide combination therapy – Disopyramide combination therapy includes beta blocker plus disopyramide or a nondihydropyridine calcium channel blocker (usually verapamil) plus disopyramide. Combinations using disopyramide are not commonly used in pediatric patients, and data are limited, but its use may be applicable in the older adolescent as an option in patients unable to tolerate the combination of beta blocker plus nondihydropyridine calcium channel blocker.

There is generally no role for using three drugs (eg, beta blockers, verapamil, and disopyramide) simultaneously.

●Other agents – We do not use the cardiac myosin inhibitor mavacamten in pediatric patients with HCM as safety data in children are lacking and it is not approved for use in pediatric patients. Its use in adults with HCM is discussed separately. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Myosin inhibitors'.)

●Surgical myectomy – An alternative to combination therapy is surgical myectomy, which is offered at a few highly specialized centers. However, most pediatric centers reserve referral for myectomy to patients who have symptoms and/or severe LVOT obstruction despite maximally tolerated medical therapy. This is rare in pediatric patients with HCM. (See 'Septal reduction therapy' below.)

Patients without obstruction

Asymptomatic patients — Asymptomatic patients without LVOT obstruction generally do not require any specific therapy. These patients can be managed expectantly with clinical observation and periodic echocardiography to detect changes in symptoms and/or development of a LVOT gradient that may warrant therapy.

Symptomatic patients

●Heart failure symptoms – In the absence of LVOT obstruction, HF symptoms (eg, dyspnea, fatigue, poor feeding, poor growth) are generally caused by diastolic dysfunction and therefore treatment options are limited. HF symptoms are uncommon in pediatric patients with sarcomeric HCM who typically have no or only mild symptoms during childhood and adolescence. HF occurs more commonly in children who have HCM as part of an underlying syndrome or inborn error of metabolism.

For patients without significant obstruction who have HF and volume overload, diuretic therapy may be used cautiously and is often effective in low doses transiently or on an as-needed basis. Diuretics should be given at the lowest effective dose to relieve symptoms and adjusted to maintain an optimal fluid balance thereafter. Patients who begin diuretic therapy should be monitored for signs of obstruction and electrolyte depletion. If signs of obstruction develop, diuretics should be discontinued. (See "Heart failure in children: Management", section on 'Diuretics'.)

●Chest discomfort – Patients with nonobstructed HCM may experience chest discomfort, which is thought to be caused by abnormal myocardial blood flow and microvascular or small vessel ischemia. Patients with new-onset or severe chest pain should undergo a thorough evaluation, including electrocardiogram (ECG) and other tests as needed based upon the presentation.

In the absence of another identified cause, chest discomfort in this setting is usually attributed to microvascular or small vessel ischemia. This is generally treated with a nondihydropyridine calcium channel (usually verapamil). The typical approach is to start with a low dose and increase until control of chest pain is satisfactory. Additional details are provided separately. (See "Hypertrophic cardiomyopathy: Management of patients without outflow tract obstruction", section on 'Chest discomfort'.)

PATIENTS WITH REFRACTORY SYMPTOMS — A small minority of pediatric patients have refractory symptoms despite optimal medical therapy. Treatment options for such patients include septal reduction therapy and heart transplantation.

Septal reduction therapy

●Surgical myectomy – Surgical myectomy is an option for patients with HCM with moderate or severe LV outflow tract (LVOT) obstruction (ie, gradient ≥50 mmHg at rest or with provocation) who have persistent symptoms and impaired quality of life despite optimal medical therapy. However, criteria for selecting candidates for myectomy are not standardized and may vary from center to center. Surgical myectomy should only be performed at centers experienced with the procedure.

The risks of surgical myectomy include aortic valve injury, heart block, ventricular septal defect, and mitral valve regurgitation. Rarely, some complications may require additional surgery (eg, aortic valve repair, pacemaker placement).

In our experience, surgical myectomy in children is effective and has an acceptably low complication rate. Studies describing surgical myectomy in pediatric HCM are composed of highly selected patients undergoing surgery at experienced centers [8-10].

In a study of 127 pediatric and young adult patients with HCM and LVOT obstruction who underwent transaortic septal myectomy, the procedure was found to be safe and effective, with a reduction in mean LVOT gradient from 89 to 6 mmHg [8]. Overall survival was 95 percent at 10 years, with a total of six patients undergoing repeat septal myectomy for recurrent symptoms. Despite this overall safety and effectiveness, it should be noted that myectomy in younger children is complicated by higher prevalence of inadequate relief of LVOT obstruction. Of the patients who needed reoperation for persistent LVOT obstruction in this study, all were under the age of 14 at initial surgery.

●Alcohol septal ablation – Alcohol septal ablation is rarely performed in pediatric patients because there is little experience with the procedure in children, there is potential risk for ventricular arrhythmia, and the long-term impact of performing the procedure in childhood is largely unknown [11]. While this procedure is generally not performed in children, it does play a role in the management of adults with HCM, as discussed separately. (See "Hypertrophic cardiomyopathy: Management of patients with outflow tract obstruction", section on 'Septal reduction therapy'.)

Heart transplantation — Referral for heart transplant evaluation is appropriate in patients with HCM who have persistent symptoms despite use of all reasonable medical and surgical therapies. Pediatric heart transplantation is discussed separately. (See "Heart failure in children: Management", section on 'Heart transplantation'.)

PREVENTION OF SUDDEN CARDIAC DEATH (ICD PLACEMENT) — ICDs are the best available therapy for patients with HCM who have survived sudden cardiac arrest or who are at high risk of ventricular arrhythmias and SCD. The general principles of ICD use and efficacy in children are similar in many respects to those in adults. However, there are some unique considerations in pediatric patients (algorithm 1). (See "Implantable cardioverter-defibrillators: Overview of indications, components, and functions".)

Special considerations for ICD implantation in children — The placement of an ICD in a preadolescent child or infant is more complicated than placement in an adolescent or young adult. Younger patients are more likely to require ICD component exchanges or extractions compared with older patients, which increases the overall risks associated with ICD therapy. The unique issues in children include:

●Potential for multiple exchanges of the device due to expected battery depletion over the child's lifetime

●Risk of lead fracture during rapid growth

●Potential for venous obstruction from multiple leads required over the child's lifetime

●Damage to the device due to increased physical activity characteristic of young children

●Smaller children have limited anatomic options for ICD generator [12]

The use of subcutaneous ICD systems that do not require transvenous lead placement has been reported in pediatric patients and may represent an alternative in certain cases [13]; however, long-term efficacy and safety are not yet well demonstrated in this patient population [14].

Secondary prevention — For pediatric patients with documented evidence of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) or who are resuscitated from sudden cardiac arrest due to VT or VF, we recommend ICD placement for secondary prevention of SCD (algorithm 1). This recommendation applies across age groups and diagnoses (eg, nonsyndromic and syndromic HCM), though ICDs are rarely placed in children less than five years of age due to the limitations described above. (See 'Special considerations for ICD implantation in children' above.)

Our approach is consistent with guidance from the American College of Cardiology, American Heart Association, and Pediatric and Congenital Electrophysiology Society [2,15] and is similar to the approach to secondary prevention in adults. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy", section on 'Secondary prevention of SCD'.)

There are few data on the efficacy of secondary prevention ICD implantation in children with HCM; the rationale for this approach is based on the efficacy of secondary prevention ICDs in adults and limited data in children. In one study that included children and young adults with HCM with an ICD implanted for secondary prevention, the rate of appropriate ICD interventions, which is a surrogate for prevention of SCD, was 14 percent per year [16].

Primary prevention

Indications for ICD placement — We suggest ICD placement for most patients with HCM who have ≥1 major risk factor for SCD (table 2 and algorithm 1). However, decisions regarding ICD implantation in children must consider the age and size of the patient. In preadolescent children and infants with risk factors for SCD, the complications of ICD implantation may exceed the expected benefits. In such cases, the decision to place an ICD is individualized. (See 'Special considerations for ICD implantation in children' above.)

For patients with ≥1 major risk factor who remain ambivalent or uncertain regarding ICD implantation, additional risk modifiers (eg, late gadolinium enhancement [LGE] burden on cardiovascular magnetic resonance [CMR] imaging) may be considered in the decision-making process. (See 'Other potential risk modifiers' below.)

Risk calculators can be helpful to provide a better understanding of the estimated magnitude of SCD risk, which can assist when engaging in shared decision-making (eg, in a patient with ≥1 major risk factor who is ambivalent about ICD placement). However, the available risk calculators have important limitations and should not be used as the sole basis for ICD decisions. (See 'Risk models and calculators' below.)

Pediatric major risk factors — The four major risk factors for SCD in pediatric patients with HCM are (table 2) [2]:

●Massive left ventricular hypertrophy (LVH) – Similar to the adult approach, massive LVH is an important risk factor for SCD in pediatric patients with HCM and is a common factor prompting ICD placement [2,17-21]. Massive LVH can be defined using an absolute cut-off (septal thickness ≥30 mm) or z-score. However, consensus is lacking regarding which z-score cut-off should be used to define massive LVH in the context of SCD risk assessment. We generally use a z-score of >10 when LVH is the sole criterion prompting ICD placement but might consider a lower threshold if the child has other concerning findings. Other experts use z-scores of >8 or >6 as the cut-off for consideration of ICD placement [18,19]. In a study of 128 children <19 years old with HCM, septal thickness >190 percent above the 95^th percentile for age (which roughly corresponds to a z-score >10) was an independent predictor of SCD, with a sensitivity of 91 percent and a specificity of 78 percent [18].

●Unexplained syncope – Unexplained syncope is another important risk factor that is predictive of SCD in both adult and pediatric patients with HCM [2,20,22,23].

●NSVT on ambulatory monitoring – In pediatric patients, nonsustained ventricular tachycardia (NSVT) is a strong predictor of SCD, and it is considered a major risk factor [2,20,23-25]. This is somewhat different from the adult approach, in which NSVT on ambulatory monitoring is considered a risk modifier. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Risk modifiers'.)

●Family history of HCM-related SCD – The available studies have reached variable conclusions regarding the prognostic value of family history. Family history of HCM-related SCD predicted SCD in some studies [26] but not others [20]. This may be due to differences in how the different studies defined "positive family history." Nevertheless, it is considered a major risk factor for the purpose of risk stratification [2].

Based on the available data, major risk factors identified in adult patients appear to have generally similar predictive value in pediatric patients, though there are some important distinctions. For example, NSVT is considered a major risk factor in children whereas it is considered a risk modifier in adult patients [2,17]. In addition, while end-stage HCM (LV ejection fraction [LVEF] <50 percent) and LV apical aneurysms are considered major risk factors in adult patients, they are uncommon in pediatric patients, and there are insufficient data to establish their independent value for predicting SCD [2,27]. Nevertheless, based on data in adults, it may be appropriate to consider these markers associated with increased arrhythmic risk. Risk factors for SCD in adults with HCM continue to evolve and different guidelines use different approaches to risk stratification. Risk stratification in adult patients is discussed in detail separately. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".)

Additional data supporting the use of these four major risk factors to inform ICD decisions in pediatric patients with HCM are described below. (See 'Efficacy and complications of ICDs' below.)

Other potential risk modifiers — The following additional factors may be considered when assessing risk of SCD in the context of ICD decision-making. The data on each of these factors are insufficient to consider ICD placement solely based on one of these variables. However, it may be appropriate to consider these factors as part of the entire clinical risk profile of the patient.

●Late gadolinium enhancement burden – While not considered a major risk factor, high LGE burden (eg, ≥15 percent of LV mass) on CMR appears to correlate with disease severity and SCD risk in adult patients. There are fewer data in pediatric patients, and the role that LGE burden plays in pediatric risk stratification is less clear. (See "Hypertrophic cardiomyopathy in children: Clinical manifestations and diagnosis", section on 'Additional testing' and "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Risk modifiers'.)

●LV apical aneurysm and systolic dysfunction (LVEF <50 percent) – Based on adult data, scarred LV apical aneurysm and the development of systolic dysfunction with LVEF <50 percent are both associated with increased risk for SCD. However, these findings are uncommon in children with HCM, and their role in risk prediction is less certain. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Established major risk markers'.)

●Left atrial size and LV outflow tract (LVOT) gradient – These two risk markers have been evaluated in pediatric HCM studies but there is no clear consensus about whether either one is an independent risk factor for SCD. A limitation of including LVOT gradient as a risk factor is that it is treatable and highly modifiable. Left atrial size can be challenging to accurately derive. Nevertheless, left atrial size and LVOT gradient are included in most of the available risk models and calculators discussed below. (See 'Risk models and calculators' below.)

Risk models and calculators — There may be no "one size fits all" approach to risk stratification that can be universally applied to all pediatric patients, given the considerable variation in size and level of maturation among pediatric patients with HCM. Risk models have been developed with the aim of providing more individualized estimation of the five-year risk of SCD.

The available risk calculator tools have important limitations (limited or no prospective validation, relatively poor sensitivity, poor correlation between different tools). Thus, we do not advise using these tools as the sole method for making ICD decisions. In our practice, we rely primarily on the four major risk factors listed in the table (table 2) to identify candidates for ICD placement. Nevertheless, web-based risk calculators can be useful tools to provide a better understanding of estimated magnitude of SCD risk, which can assist in shared decision-making in patients with ≥1 major risk factor who are ambivalent about ICD placement.

Risk models for the prediction of SCD in patients with HCM include:

●Adult risk calculators – Risk calculators that have been validated in adult patients include the European Society of Cardiology HCM Risk-SCD calculator and the American Heart Association HCM SCD calculator. These tools can be used in adolescent patients ≥16 years old. The main limitation of these tools is that they were derived from and validated in cohorts with relatively few adolescent patients, so they may not accurately estimate risk in this population. These risk models are discussed in greater detail separately. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death", section on 'Risk prediction model'.)

●HCM Risk-Kids calculator – The HCM Risk-Kids calculator was developed from a cohort of 1024 children aged ≤16 years with HCM [22]. The model's variables include unexplained syncope, maximal LV wall thickness, left atrial diameter, LVOT gradient, and NSVT. The model generates a risk score (similar to the HCM Risk-SCD score in adults) and was shown to have moderate discrimination for predicting SCD (C-statistic 0.69) [22]. It has not been independently validated.

●PRIMaCY risk calculator – The Precision Medicine for Cardiomyopathy (PRIMaCY) pediatric HCM risk model was derived from 572 patients enrolled in an international registry [20]. The model's variables include age at diagnosis, NSVT, unexplained syncope, septal and posterior wall thickness z-scores, left atrial diameter z-score, LVOT gradient, and genotype. In the derivation cohort, the PRIMaCY model had moderate discrimination for predicting SCD events (C-statistic 0.76). Similar discrimination (C-statistic 0.72) was observed in a separate validation cohort, consisting of 285 phenotype-positive patients from the Sarcomeric Human Cardiomyopathy Registry (ShaRe) [20]. Of note, family history of SCD was not an independent predictor of SCD in this model, and, in contrast to most other studies, there was an inverse association between LVOT gradient and SCD once the gradient was >100 mmHg.

Efficacy and complications of ICDs — The approach outlined above is supported by limited retrospective studies in children [16,17,28,29], and indirect evidence from studies in adult patients with HCM. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".)

The available studies mostly examined the effects of ICDs in adolescents and young adults. In preadolescent children, the benefits and risks of ICD implantation are not well-described. While numerous risk factors have been reported to be predictive of SCD and several multivariable risk prediction models are available, we generally rely on the four major risk factors that are consistently associated with risk of SCD in children with HCM (table 2).

The performance of the four major pediatric risk factors in predicting life-threatening arrhythmias was demonstrated in a cohort of 146 patients <20 years old with HCM, 60 of whom underwent ICD placement for primary prevention based upon one or more of these risk factors [17]. Over a mean follow-up of 5.8 years, 10 patients (9 patients with an ICD and 1 high-risk patient who declined primary prevention ICD) experienced ventricular tachyarrhythmias requiring intervention. The sensitivity of these risk factors for predicting ventricular tachyarrhythmias was 100 percent, and the five-year risk of an appropriate ICD discharge among patients with ≥1 risk factor was 14 percent.

In another study of 474 consecutive patients aged 7 to 29 years (mean 20 years) managed at two large referral centers, ICDs were implanted for primary prevention in 231 patients at the discretion of cardiologists who predominantly used the factors of LV hypertrophy, family history of HCM-related SCD, NSVT, unexplained syncope, and hypotensive response to exercise [28]. Over a median follow-up of six years, ventricular tachyarrhythmias were successfully aborted by appropriate defibrillator interventions in 31 patents (13 percent). Device-related complications occurred in 60 patients (26 percent) at a rate of 1.8 percent per year. The most common complication was inappropriate shock, which occurred in 42 patients (18 percent) and was equally common in patients with ICDs placed for primary versus secondary prevention. Notably, of the 42 patients experiencing inappropriate shocks, 13 (31 percent) also had appropriate device interventions. Other complications included lead fracture, dislodgements, or insulation defect without inappropriate shock (n = 11); hematoma/thrombosis (n = 2); pocket revision (n = 2); infection (n = 1); generator malfunction or replacement because of manufacturer's advisory or recall (n = 1); and perforation of right atrium during lead extraction (n = 1).

In a registry study of 224 pediatric patients (mean age 14.5 years) who underwent ICD implantation at the discretion of the managing pediatric cardiologists for secondary or primary prevention, the reasons for primary prevention ICD implantation included extreme LVH (62 percent), syncope (38 percent), family history of HCM-related SCD (41 percent), hypotensive response to exercise (18 percent), NSVT (12 percent), and other reasons (1 percent) [16]. One criterion was present in 47 percent of patients; the remainder had ≥2 criteria. Appropriate ICD interventions in the primary prevention group occurred most frequently in patients with massive LVH and less frequently in patients with a history of syncope, family history of HCM-related death, NSVT, and hypotensive response to exercise. There were no appropriate ICD therapies delivered in the group of patients with "other" indications for ICD implantation. The rate of primary prevention ICD therapies for patients with one, two, or three criteria was 3.1, 2.9, and 3.8 interventions per 100 patient years, respectively.

Antiarrhythmic drug therapy — Antiarrhythmic agents may be used in appropriate patients who have either frequent VT and are not candidates for ICD or who experience multiple appropriate ICD shocks [2]. However, antiarrhythmic medications should not be used alone in lieu of ICD placement in patients considered to be at high risk for SCD.

FOLLOW-UP — The frequency of follow-up depends upon whether the child has clinical evidence of HCM:

●For pediatric patients with phenotypic HCM (ie, those with evidence of LV hypertrophy [LVH] on cardiac imaging), particularly those on medication, we suggest clinical evaluation every 6 to 12 months with ECG and echocardiogram. Additional testing, such as ambulatory ECG monitoring, exercise testing, and CMR, are variable based on the specific patient.

●For those who are genotype-positive/phenotype-negative (G+ P-; sometimes called preclinical HCM), we suggest evaluation including ECG and echocardiogram annually, particularly during the adolescent years when patients most commonly develop symptoms. Current adult guidelines recommend clinical assessment and testing, including ECG and echocardiogram, every one to two years or as indicated by symptoms [2,30]. G+ P- individuals are typically identified through cascade testing after a family member is diagnosed with HCM. Additional information on the clinical evaluation and follow-up for these individuals is provided separately. (See "Hypertrophic cardiomyopathy in children: Clinical manifestations and diagnosis", section on 'Evaluation of first-degree relatives'.)

LONG-TERM HEALTH MAINTENANCE — The following sections outline key aspects of long-term health care maintenance in children with HCM.

Immunizations — Children with HCM should receive all routine childhood vaccinations, including pneumococcal vaccine, yearly influenza vaccine, COVID-19 vaccine, and respiratory syncytial virus (RSV) immunoprophylaxis for eligible infants. (See "Standard immunizations for children and adolescents: Overview" and "Pneumococcal vaccination in children" and "Seasonal influenza in children: Prevention with vaccines" and "COVID-19: Vaccines", section on 'Children' and "Respiratory syncytial virus infection: Prevention in infants and children".)

Monitoring of growth parameters — It is important to monitor growth and development in children with HCM, as it is in all children. Failure to thrive may be the main clinical sign of HF in infants and children. (See "Normal growth patterns in infants and prepubertal children".)

Monitoring for cardiac symptoms — Between visits with the cardiac specialist, the primary care provider should monitor for symptoms related to LV outflow tract (LVOT) obstruction or HF. If the patient develops new or worsening symptoms of chest pain, presyncope, syncope, palpitations, or HF symptoms (eg, poor feeding, failure to thrive, tachypnea, easy fatigability), the patient should be promptly referred to the specialist for cardiac evaluation.

Antibiotic prophylaxis — Routine antibiotic prophylaxis for the prevention of bacterial endocarditis is not necessary for most children with HCM unless there are other factors that place the child at high risk [31]. Risk factors for bacterial endocarditis are reviewed in detail separately. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

Recreational exercise and competitive sports participation — Due to the potential risk of SCD associated with exercise in patients with HCM, consideration of appropriate activity restriction is an important component of patient management. However, for most patients with HCM, mild- to moderate-intensity recreational exercise is beneficial and should be encouraged [2,32]. Children with HCM can typically participate in physical education at school, with the exception that the child should not be graded, timed, or scored for performance. The availability of automatic external defibrillators near playgrounds and/or athletic facilities can provide an additional level of reassurance [2]. Activity restriction in patients with HCM is discussed in greater detail separately. (See "Athletes: Overview of sudden cardiac death risk and sport participation", section on 'Hypertrophic cardiomyopathy'.)

Planning of noncardiac surgery — Children with HCM who have a significant LVOT gradient are at increased risk for adverse events (eg, acute LVOT obstruction with hemodynamic collapse) when undergoing surgery and other procedures under anesthesia. Perioperative planning includes consultation with cardiac anesthesia, coordination with the cardiologist, and appropriate postprocedural monitoring. Management of acute LVOT obstruction, as well as perioperative planning and management, are discussed separately. (See "Anesthesia for patients with hypertrophic cardiomyopathy undergoing noncardiac surgery".)

PROGNOSIS — The prognosis for children with HCM depends on the age at diagnosis, degree of symptoms at diagnosis, and whether there are associated conditions [28,33-37].

●Adolescents with nonsyndromic HCM – Patients who are diagnosed with HCM in adolescence usually have no or minor symptoms at the time of diagnosis. For such patients, outcomes are generally very good. With contemporary management strategies that employ appropriate medical therapy and use of ICDs, the risk of mortality is low [28,36,38]. In a study of 474 consecutive patients between the ages of 7 and 29 years at two referral institutions, five-year survival was >95 percent, with a similar proportion experiencing no or mild symptoms [28]. The main cause of death in older children and adolescents with HCM is malignant arrhythmias, which frequently have no prodrome.

A report from the International Paediatic HCM Consortium (IPHC) described the outcomes of 568 adolescent patients (ages 12 to 16 years) with nonsyndromic HCM, of whom three-quarters were asymptomatic at presentation [36]. Over an average follow-up of 4.4 years, 4 percent experienced SCD, 1 percent underwent cardiac transplantation, 1 percent died from HF or other cardiovascular complications (excluding SCD), and 1.5 percent died from unknown or noncardiovascular causes.

In patients who present with symptoms, the prognosis appears to be worse. In a report of 100 Italian children diagnosed with HCM (mean age 12.2 years at diagnosis), of whom 42 percent were symptomatic at diagnosis, nearly 20 percent experienced major adverse cardiac events over an average follow-up of 9.2 years [38]. This included SCD in 14 percent, HF-related death in 3 percent, and heart transplantation in 2 percent. Whether these data are applicable to other heterogenous pediatric HCM patient populations is uncertain. (See "Hypertrophic cardiomyopathy: Risk stratification for sudden cardiac death".)

●Preadolescent children with nonsyndromic HCM – For patients diagnosed with nonsyndromic HCM before adolescence, the long-term prognosis is generally good and similar to that of adolescents with nonsyndromic HCM. However, this group is at risk for experiencing adverse cardiovascular events at a younger age. This was demonstrated in the report from the IPHC discussed above, which described long-term outcomes of 639 preadolescent patients (ages 1 to <12 years) with nonsyndromic HCM; approximately 80 percent were asymptomatic at presentation [36]. Over an average follow-up of 5.6 years, 5 percent experienced SCD, 3 percent underwent cardiac transplantation, and 1 percent died from HF or other cardiovascular complications (excluding SCD). The average age at time of death or transplant was 12 years old.

●Syndromic HCM and HCM in infancy – Patients diagnosed with HCM in infancy commonly have an underlying syndrome or metabolic disorder (ie, inborn errors of metabolism [IEM] and/or multiple congenital anomaly [MCA] syndromes) (table 1). The prognosis for this population is less favorable compared with sarcomeric HCM presenting later in childhood or adolescence [33-35,39,40]. Mortality in these patients is most commonly due to HF and other non-SCD causes.

In a series of 855 patients from the Pediatric Cardiomyopathy Registry, two-year transplant-free survival was 70 percent for patients with infantile HCM compared with 92 to 98 percent for those diagnosed later in childhood [41]. Among patients with IEM and MCA syndromes, one-year survival rates were 54 and 82, respectively. SCD accounted for only 44 percent of deaths that occurred in patients with infantile HCM, whereas in older patients, all of the deaths that occurred were due to SCD.

Another report from the Pediatric Cardiomyopathy Registry found that children with HCM associated with IEM or MCA syndromes who presented in infancy had a particularly poor prognosis, with five-year survival rates of 26 and 66 percent, respectively [39]. Additional independent predictors of death or heart transplantation included congestive HF symptoms at the time of diagnosis and low weight and body mass index for age.

In a cohort from the United Kingdom of 687 children diagnosed with HCM between 1980 and 2017 (median age at diagnosis 5.2 years; 23 percent diagnosed at age <1 year), freedom from death or transplantation at five years after diagnosis was 91 percent for the entire cohort, a finding which remained consistent across different eras [35]. Children diagnosed during infancy or with associated IEM had worse five-year survival (81 and 66 percent, respectively).

In a study of 188 patients with HCM associated with RAS/MAPK pathway syndromes (chiefly Noonan syndrome [88 percent] and Costello syndrome [7 percent]), the mean age at diagnosis was 11 months [40]. During average follow-up of 4.8 years, 18 patients (10 percent) died and five patients (3 percent) underwent heart transplantation. HF was the most common cause of death.

Outcomes for HCM are generally better than those for other cardiomyopathies, although presence of restrictive physiology portends a poorer outcome than for HCM alone [42].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Cardiomyopathy".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Hypertrophic cardiomyopathy in adults (The Basics)" and "Patient education: Hypertrophic cardiomyopathy in children (The Basics)")

●Beyond the Basics topic (see "Patient education: Hypertrophic cardiomyopathy (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Treatment goals – The goals of management in patients with hypertrophic cardiomyopathy (HCM) are to reduce symptoms, reduce the left ventricular outflow tract (LVOT) gradient, preserve LV function, prevent sudden cardiac death (SCD), and prolong survival. (See 'Treatment goals' above.)

●Initial management for patients with obstruction

•Indications for therapy – For patients with moderate to severe LVOT obstruction (ie, gradient ≥50 mmHg at rest or provocation), regardless of symptoms, we suggest pharmacologic treatment rather than observation (Grade 2C). However, there is no standardized approach and other experts may prefer to avoid pharmacologic therapy in asymptomatic children, particularly if a reliable assessment of symptoms can be obtained. (See 'Patients with obstruction' above.)

•Choice of agent – For most patients, we suggest beta blockers for first-line therapy rather than other agents (Grade 2C). The preference for beta blockers is based on the ease of dosing and greater experience with these agents in children. A nondihydropyridine calcium channel blocker (usually verapamil) is a reasonable alternative option for monotherapy in patients ≥1 year who are intolerant of beta blockers due to side effects. Verapamil is generally avoided in infants <12 months due to concerns for apnea, hypotension, and cardiac arrest. Disopyramide is another reasonable alternative to beta blocker therapy, though it is not commonly used in pediatric patients. (See 'Symptomatic patients' above.)

●Patients without obstruction

•Asymptomatic patients – Asymptomatic patients without LVOT obstruction generally do not require any specific therapy. These patients can be managed expectantly. (See 'Patients without obstruction' above.)

•Symptomatic patients – In the absence of LVOT obstruction, heart failure (HF) symptoms (eg, dyspnea, fatigue, poor feeding, poor growth) are generally caused by diastolic dysfunction, and, therefore, treatment options are limited. For patients with volume overload, diuretic therapy may be used cautiously. (See 'Symptomatic patients' above and "Heart failure in children: Management", section on 'Diuretics'.)

●Patients with refractory symptoms – A small minority of pediatric patients have refractory symptoms despite optimal medical therapy. Treatment options for such patients include septal reduction therapy (ie, surgical myectomy) and heart transplantation. (See 'Septal reduction therapy' above and 'Heart transplantation' above.)

●Prevention of sudden cardiac death – Implantable cardioverter-defibrillators (ICDs) are the best available therapy for patients with HCM who are at high risk of SCD. Our general approach to risk assessment and identifying candidates for ICD placement is as follows (algorithm 1) (see 'Prevention of sudden cardiac death (ICD placement)' above):

•Regardless of the age or size of the child, the first step is to assess the patient's risk of SCD (table 2). (See 'Pediatric major risk factors' above.)

•For patients who have experienced a prior episode of sustained ventricular tachycardia (VT) or sudden cardiac arrest, we recommend ICD placement for secondary prevention of SCD (Grade 1B) (algorithm 1). (See 'Secondary prevention' above and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".)

•In addition, for adolescent patients with HCM who have ≥1 major risk factor for SCD (table 2), we suggest ICD placement for primary prevention of SCD (Grade 2C) (algorithm 1). This decision should be made in the context of shared decision-making; determining an estimate of the magnitude of five-year SCD risk with risk calculators may provide additional information to inform on ICD decision-making. (See 'Primary prevention' above.)

•Decisions in preadolescent patients are individualized, taking into account the age and size of the child as well as the estimated risk of SCD. (See 'Primary prevention' above and 'Special considerations for ICD implantation in children' above.)

●Follow-up – We suggest that pediatric patients with phenotypic disease, particularly those on medication, should have a clinical evaluation every 6 to 12 months with ECG and echocardiogram. For those who are genotype-positive/phenotype-negative, evaluation including ECG and echocardiogram is recommended annually, particularly during the adolescent years when patients most commonly develop symptoms. (See 'Follow-up' above.)

●Long-term health maintenance – Important aspects of long-term health care maintenance in children with HCM include administering routine childhood vaccinations, monitoring growth parameters, monitoring for cardiac symptoms, providing guidance regarding exercise and sports participation, and planning of noncardiac surgery. Antibiotic prophylaxis for bacterial endocarditis is generally not necessary for children with HCM. (See 'Long-term health maintenance' above.)

●Prognosis – The prognosis for children with HCM depends on the age at diagnosis, degree of symptoms, and the presence of associated conditions. In older children and adolescents with sarcomeric HCM, who typically have no or minor symptoms at the time of diagnosis, outcomes are generally very good. By contrast, the prognosis is less favorable in patients diagnosed with HCM in infancy; these patients often have an underlying inborn error of metabolism (IEM) and/or multiple congenital anomaly (MCA) syndrome (table 1). (See 'Prognosis' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges John L Jefferies, MD, MPH, FACC, FAHA, who contributed to earlier versions of this topic review.