Pediatric Diagnosis and Management

Abstract

Hypertrophic cardiomyopathy in children manifests important differences with regard to the causes, findings, response to therapy, and outcomes compared to this disease in adults. Management and diagnosis in infants and young children in particular are associated with unique considerations. Etiology is an important determinant of survival, particularly in the youngest patients, and pursuit of a specific cause is therefore requisite. Diagnosis is more challenging because of a variety of metabolic and syndromic disorders that present with the hypertrophic cardiomyopathy phenotype in infancy. Diagnostic criteria commonly used in adults must be scaled to body size in children. There is considerable clinical value in genetic characterization in children with hypertrophic cardiomyopathy, and the resulting cost-benefit ratio for genetic testing is therefore far more favorable than in adults. Most of the available information concerning response to therapy and potential methods of preventing sudden cardiac death has been developed in adult patients, but management of children requires consideration of the differences in age-specific risk-to-benefit ratios such as higher complication rates for implantable defibrillators. Sports participation is a particularly challenging issue in adolescents because of the high percentage of participation and the important social role of these activities. These young patients experience high rates of adverse psychological response to both exercise restrictions and defibrillator implantation. Overall, both diagnosis and therapy require age stratification.

Questions

• 1. The definition of hypertrophic cardiomyopathy in childhood is the absence of a hemodynamic cause of left ventricular hypertrophy in conjunction with:

  • A. Left ventricular wall thickness z-score >2

  • B. Presence of known pathogenic sarcomeric gene

  • C. Left ventricular wall thickness z-score >4

  • D. A and B

  • E. B and C

• Correct answer = C. The disease is defined on the basis of severity of hypertrophy and does not depend on etiology. Based on incidence of disease, the AHA and ESC published criteria of z-score >2 are wrong, and to avoid overdiagnosis, a z-score >4–5 is used to make the diagnosis.

• 2. The incidence of sarcomeric hypertrophic cardiomyopathy in childhood is:

  • A. >1/500

  • B. <1/500

  • C. <1/1000

  • D. <1/10,000

  • E. <1/100,000

• Correct answer = E. Although the rate of pathogenic sarcomeric gene carriage in the population is estimated at 1/500, onset of the phenotype is uncommon prior to adolescence. The incidence of all forms of HCM in childhood is 1/100,000, but in fact in preadolescents, non-familial hypertrophic cardiomyopathy is more common than familial hypertrophic cardiomyopathy.

• 3. Etiologic diagnosis of hypertrophic cardiomyopathy is particularly important in infancy because:

  • A. Etiology-specific therapies are available for some diseases.

  • B. Decisions concerning surgical indications are etiology-specific.

  • C. Spontaneous resolution is characteristic of some forms of infantile hypertrophic cardiomyopathy.

  • D. All of the above.

  • E. A and C.

• Correct answer = E. A number of the inborn errors of metabolism have specific therapies that need to be initiated early in life in order to maximize long-term benefit, a situation that is likely to become more important over time as new therapies become available. Infants of diabetic mothers are expected to have full resolution of hypertrophic cardiomyopathy within months, and only supportive care is advised.

• 4. Therapeutic decisions in the management of hypertrophic cardiomyopathy associated with Noonan syndrome should take into consideration which of the following:

  • A. Infants with congestive heart failure during infancy have <50% survival to 1 year.

  • B. Biventricular outflow tract obstruction is more common than in other forms of hypertrophic cardiomyopathy.

  • C. Most childhood deaths in Noonan syndrome are related to arrhythmias.

  • D. A and B.

  • E. B and C.

• Correct answer = D. Less than 1/3 of infants with Noonan -related hypertrophic cardiomyopathy who manifest congestive heart failure survive until 1 year of age and congestive heart failure is responsible for their demise in almost all cases. Because of the high incidence of pulmonary stenosis associated with Noonan syndrome, the finding of biventricular outflow tract obstruction should always raise the question as to whether Noonan syndrome is responsible.

• 5. The presence of a pathogenic sarcomeric gene in the absence of sufficient myocardial hypertrophy to meet criteria for hypertrophic cardiomyopathy is significantly associated with which of the following:

  • A. An increased incidence of sudden cardiac death

  • B. Increased incidence of exercise-related adverse events

  • C. Diminished myocardial relaxation velocities

  • D. A and B

  • E. A and C

• Correct answer = C. More than 50–80% of carriers of sarcomeric gene mutations associated with hypertrophic cardiomyopathy have evidence of diminished myocardial relaxation velocities. However, in the absence of hypertrophy, no increased propensity to arrhythmia or sudden death has been reported.

• 6. Potential individual benefits of gene testing in phenotype-negative first-degree relatives of subjects with hypertrophic cardiomyopathy for whom the pathogenic gene has been defined include which of the following:

  • A. Prevention of transmission of the gene

  • B. Eligibility for mutation-specific clinical trials and therapies

  • C. Elimination of longitudinal monitoring for evolution of the disease

  • D. Determination of whether his or her offspring requires screening for the phenotype

  • E. All of the above

• Correct answer = E. Embryo preselection can prevent disease transmission and is now a commonly available intervention. Clinical trials of drugs that may prevent disease expression are already under way. Neither the individual nor his or her first- and second-degree relatives who would otherwise require periodic screening for new disease expression can be excluded from this need unlessthey do not carry the gene.

• 7. Indications for myectomy in patients with hypertrophic cardiomyopathy include which of the following:

  • A. NYHA heart failure class >II unresponsive to medical therapy

  • B. Unexplained syncope or aborted sudden death

  • C. Resting left ventricular outflow tract gradient >80 mm Hg unresponsive to medical therapy

  • D. Exercise-induced ventricular outflow tract gradient >100 mm Hg

  • E. All of the above

• Correct answer = A. Myectomy has been shown to result in improved clinical status but has not been found to reduce the risk of sudden death. Some patients tolerate high outflow gradients without symptoms, and therefore even high resting or inducible gradients are not considered an indication for surgery. At present, symptoms unresponsive to medical therapy are considered the only indication for surgery.

• 8. Exercise testing for inducible left ventricular outflow tract obstruction is helpful for which of the following:

  • A. Distinguishing physiologic from pathologic hypertrophy

  • B. Assessing the risk of sudden death

  • C. Evaluating the cause of exercise intolerance

  • D. Determining the need for exclusion from sports participation

  • E. Predicting the response to asynchronous pacing

• Correct answer = C. The presence of exercise-induced outflow tract obstruction creates a greater propensity for exercise intolerance and therefore helps to predict the magnitude of potential benefit that may be obtained from myectomy. However, exercise-induced outflow tract obstruction can be seen in physiologic hypertrophy, is not a known risk factor for sudden death, is not an indication for sports exclusion, and is not related to the potential hemodynamic benefits of asynchronous pacing.

• 9. Factors which interfere with the application of adult recommendations for implantable cardioverter-defibrillator (ICD) implantation for primary prevention in children include:

  • A. Lack of pediatric sudden death risk factor verification

  • B. Lower efficacy rate for ICD in children

  • C. Higher risk of adverse events related to the ICD

  • D. All of the above

  • E. A and C

• Correct answer = E. The identified risk factors are derived exclusively in adults, and insufficient pediatric data exist to verify these risk factors in children. The rate of ICD complications is considerably higher in children, but the efficacy of the ICD does not appear to be less than that in adult patients.

• 10. A difference between hypertrophic cardiomyopathy management in children vs adults is:

  • A. Digoxin is more helpful in the pediatric population.

  • B. Alcohol septal ablation is better tolerated in the pediatric population.

  • C. Genetic testing is more cost-effective in the adult population.

  • D. There is a much more diverse group of etiologies in the adult population.

  • E. None of the above.

• Correct answer: E. Genetic testing is more cost-effective in the pediatric population as there is a much more diverse group of etiologies in the pediatric population. Digoxin is relatively contraindicated in pediatric HCM patients. Alcohol septal ablation is not used in the pediatric population at this time.

• 11. A 15-year-old female with G+P- HCM status wishes to participate in competitive sailing. Which of the following statements is true?

  • A. Sailing is not a 1A sport and should be discouraged.

  • B. Her HCM status is not a contraindication to her participation in sailing.

  • C. No competitive sports are allowed for patients with G+P- HCM status.

  • D. Provided her Holter and exercise stress test are normal, she can participate and does not require follow-up until age 20 years.

  • E. None of the above.

• Correct answer: B. Pediatric patients with G+P- status do not have to avoid sports, but she should continue to have yearly echocardiograms.

• 12. An asymptomatic teenager with known HCM presents for routine follow-up at 12 weeks gestation with her first child. Which of the following statements is appropriate?

  • A. She should strongly consider elective termination because her fetus has a 50% chance of HCM.

  • B. She should strongly consider elective termination because pregnancy is not well tolerated in women with HCM.

  • C. She should not deliver vaginally unless her left ventricular outflow tract gradient is <2 m/s during Valsalva.

  • D. A fetal echo should be performed at 20 weeks of gestation; if there is no evidence of fetal hydrops, she may continue with the pregnancy.

  • E. None of the above.

• Correct answer: e. Pregnancy is usually well tolerated in asymptomatic women with HCM. There is no evidence to suggest that an LVOT>2 m/s during Valsalva is associated with the need for a cesarean delivery. Fetal hydrops is not typically associated with HCM and does not pose a risk to the mother. It is inappropriate to advise elective termination.

• 13. A 14-year-old male with a history of Friedreich ataxia presents to you for cardiac consultation. Which of the following statements are true?

  • A. There is less than a 10% that he will manifest the phenotype of HCM, but an echocardiogram is indicated.

  • B. There is a greater than 50% chance that he will manifest the phenotype of HCM.

  • C. Patients with Friedreich ataxia have a higher incidence of SCD.

  • D. Both A and C.

  • E. Both B and C.

• Correct answer: B. Patient’s with Friedreich ataxia have a >50% incidence of HCM, and they rarely present prior to the onset of neurologic symptoms, tend to manifest symmetric hypertrophy without outflow obstruction, and do not appear to be at significant risk for SCD.

• 14. Which of the following statements is true?

  • A. Parents are highly encouraged to purchase a portable AED for use at home and school.

  • B. Parents are highly encouraged to learn CPR unless their child has an implantable defibrillator.

  • C. Parents are highly encouraged to learn CPR, purchase a portable AED, and request that the school has one as well.

  • D. CPR has not demonstrated any benefit to survivability of out-of-hospital arrests in pediatric patients with HCM.

  • E. CPR should be undertaken in patients with out-of-hospital cardiac arrest regardless of the presence of an AICD.

• Correct answer: e. Patients and their families should understand that in the case of an arrest, CPR should be undertaken regardless of whether an ICD has been placed. Statistically, the odds of use of an in-home/in-school AED are limited by the average adverse event rate of ~1%/year and are further reduced by the amount of time spent in the house or class. The final decision is clearly up to the family, but in general patients who are felt to be at sufficient risk to justify continuous access to a defibrillator should have an ICD.

• 15. Which of the following would be most helpful to distinguish between HCM and athlete’s heart in an ice hockey player?

• A. Significantly decrease intensity of on and off ice training for 6 months and reimage.

• B. Cessation of all activity for 1 year and reimage.

• C. Myocardial biopsy to look for myofibril disarray.

• D. Continuation of participation in practices but not games for 1 year.

• E. Perform a cardiopulmonary stress test and if normal, can participate.

• Correct answer: A. The strongest evidence of physiologic hypertrophy (aka athlete’s heart) is significant reduction in hypertrophy in response to detraining, a process that often requires 6–12 months of relative inactivity. Cessation of all activity in a young hockey player would be helpful but will most likely have a low level of compliance and places an unnecessary and excessive limitation on the patient’s quality of life. Myocardial biopsy is both invasive and helpful only on infiltrative disorders. Practices in ice hockey are as intense if not more so than game situations where short shifts are emphasized. A normal cardiopulmonary exercise test does not rule out HCM.

• 16. Which of the following patients is most likely to have athlete’s heart?

  • A. An 18-year-old collegiate basketball player with a maximum septal thickness = 15 mm and a peak oxygen consumption >50 ml/kg/min

  • B. A 16-year-old volleyball player with a maximum septal thickness = 15 mm and inverted T waves in the left lateral leads

  • C. A 14-year-old track star with a maximum septal thickness = 20 mm and a VO2 >60 ml/kg/min

  • D. A 12-year-old sedentary child with a maximum septal thickness = 13 mm

  • E. A 14-year-old football player with a maximum septal thickness = 15 mm and a VO2 <45 ml/kg/min

• Correct answer: A. While an IVS measurement is in the gray zone between athlete’s heart and HCM, the fact that the VO2 obtained is >50 ml/kg/min is reassuring. Inverted T waves in the left precordial leads are typical for LVH with strain. An IVS measurement=20 mm is reasonably definitive for HCM. A sedentary child would not meet the definition for athlete’s heart, and a VO2<45 ml/kg/min does not suggest a highly conditioned athlete.

• 17. Which of the following management strategies has thus far been the most efficacious in preventing sudden cardiac death in children with HCM?

  • A. ICD implantation

  • B. Exercise restriction

  • C. Surgical myectomy

  • D. Alcohol septal ablation

  • E. Beta blockers

• Correct answer: A. Implantable cardioverter-defibrillator (ICD) therapy remains the only therapeutic option that is unequivocally accepted as effective for improved survival in high-risk groups by reducing the incidence of SCD. Exercise restriction is only effective theoretically. Alcohol septal ablation is not employed in the pediatric population and has not been shown to improve survival. Surgical myectomy and beta blockers are effective in symptom management but have not been shown to reduce the risk of sudden death.

• 18. Hypertrophic cardiomyopathy has been associated with which of the following genetic syndromes?

  • A. Trisomy 21

  • B. Ehlers-Danlos

  • C. Costello syndrome

  • D. Turner syndrome

  • E. Williams syndrome

• Correct answer: C. HCM is seen in up to 20–30% of patients with Noonan’s syndrome and other developmental syndromes of Ras/MAPK pathway dysregulation, the so-called RASopathies (Noonan syndrome, Costello syndrome, cardiofaciocutaneous syndrome, Noonan with multiple lentigines syndrome, and neurofibromatosis type 1). The other syndromes are not typically associated with HCM.

• 19. The typical EKG pattern in hypertrophic cardiomyopathy may include all of the following except:

  • A. Third-degree AV block

  • B. Left ventricular hypertrophy

  • C. Inverted T waves in the left precordial leads

  • D. Right bundle branch block

  • E. None of the above

• Correct answer: A. Complete heart block is associated with babies born to mothers with anti-Ro and anti-La antibodies, surgery, and Lyme disease. The EKG in HCM is abnormal >90% of the time with hallmark abnormalities including voltage criteria for LVH with or without strain, RBBB, left atrial enlargement, and deep Q waves.

• 20. What maneuver would you expect to increase the outflow murmur in this patient?

  • A. Knee to chest in supine position

  • B. Isometric handgrip

  • C. Phenylephrine

  • D. Amyl nitrate

  • E. None of the above

• Correct answer: D. Amyl nitrate will decrease afterload, intensifying the dynamic left ventricular outflow tract murmur of HCM. Isometric handgrip and phenylephrine increase afterload, lessening the dynamic murmur of LVOT obstruction. Knee to chest will have a similar effect as squatting.