Case

Hi doctor, this is the check-in desk calling from the waiting room. I have a mother here who has brought her 8-year old son with an electrocardiogram (ECG) in her hands stating that she needs to have this read before she can get a prescription for ADHD medications. You have never seen this child before, but the mother is insisting that the ECG be read today as the child is starting back at school next week. She says her pediatrician won’t allow her to get the prescription unless a cardiologist clears him. I’ve tried to get her to schedule an appointment, but she keeps insisting that all she needs is the ECG to be read by someone to clear her son for stimulant medications. Does this sound like something you can do?

What am I thinking?

To be honest, I am as frustrated as the mother. ECG screening is a controversial topic for a variety of reasons. While seemingly simple, the questions posed raise a number of complex issues. Like many tests, the ECG has strengths and limitations when it comes to providing answers to the type of question posed by this mother. Sometimes it can give a specific answer, but often, it may raise issues well beyond the question for which it was performed. Hence, one needs to be cautious, and not take the matter too lightly. Without understanding the context of the ECG, it can provide false reassurance or send the physician down a deep rabbit hole of tests with no clear end in sight. Therefore, to use an often misused and overused dictum: “Clinical correlation is always advised and necessary.” Which is to say that the context is key. ( Continued at end of chapter ).

History and physical

In the scenario presented, there would not be an opportunity to perform a thorough history and physician without an appointment. However, the purpose of this section is to highlight cardiac screening in the young and the type of evaluation it involves. The American Academy of Pediatrics has a preparticipation physical evaluation that includes a helpful history screening questions in the heart health section of the form. While the questions are purposefully somewhat vague, “yes” answers to the questions may prompt more questions and further evaluation.

Have you ever passed out or nearly passed out during or after exercise?

Syncope during exercise is concerning for both structural and arrhythmic diagnoses for sudden cardiac death. Further questions into the timing of syncope, the circumstances, emergency response, etc. will be crucial in determining if this patient may have a condition that may be potentially lethal and associated with sudden death. Most structural heart disease and inherited arrhythmia syndromes can present as syncope with exercise, and this one symptom should always be taken very seriously and be considered an aborted sudden death episode until otherwise disproven.

Have you ever had discomfort, pain, tightness or pressure in your chest during exercise?

The key to this question is during exercise. Chest pain is a common complaint in young people and adolescents, usually occurring at rest and can be reproduced on physical exam. However, when present during exercise, chest pain should be considered a symptom pointing to a serious heart condition like coronary ischemia, which, in children, can be caused by conditions such as anomalous origin or course of the coronary artery, hypertrophic cardiomyopathy, and dilated cardiomyopathy.

Does your heart ever race, flutter in your chest, or skip beats (irregular beats) during exercise?

This question is attempting to identify conditions in which exercise may predispose to an arrhythmia such as Wolff-Parkinson-White Syndrome, Hypertrophic Cardiomyopathy (HCM), Arrhythmogenic Right Ventricular Dysplasia (ARVD), and Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). This question is particularly important for CPVT as an increased catecholamine state is what predisposes to arrhythmia in CPVT. Also, CPVT patients may sometimes have PVCs on the ECG, but it is not uncommon for the ECG (and physical examination) to be normal in these patients. Patients can be diagnosed by exercise stress test with a pathognomonic pattern of bidirectional ventricular tachycardia (Reference to Chapter 18, Figure 1).

Has a doctor ever told you that you have any heart problems?; Has a doctor ever requested a test for your heart? For example, electrocardiography (ECG) or echocardiography?

These questions are driving toward patients who have been diagnosed with either congenital or acquired heart disease and require further evaluation for physical activity by their cardiologists. Patients who mark yes to these questions should be assessed by a cardiologist and may indeed require further testing to assess fitness for physical activity.

Do you get light-headed or feel short of breath earlier than your friends during exercise?

This question is attempting to determine whether the stress of exercise can unmask an underlying serious heart condition and on the heart’s ability to compensate for exercise. In patients with structural heart disease, this can manifest as feeling light-headed or becoming short of breath faster than peers. This may be true in patients with hypertrophic cardiomyopathy or anomalous origin of the coronary artery and maybe the first sign of a cardiac problem.

Have you ever had a seizure?

While seizure activity is certainly a concern of neurologic conditions, the question is posed in the cardiac health history to determine any prior presentation of cardiac arrest lading to cerebral anoxia that, in turn, can cause a seizure. This is particularly helpful in assessing arrhythmia-related diseases (such as long QT syndrome, short QT syndrome, Brugada syndrome, ARVD, and CPVT) where, for poorly understood reasons, arrhythmias can be nonsustained and self-terminate. Thus, the patient can have recurrent “seizures” and can be mistakenly treated for epilepsy. Other cardiac conditions that may present with arrhythmic arrest can also be manifest with seizure-like activity. For patients who do have a history of seizure, it is helpful to further define their neurologic workup and whether a seizure disorder was diagnosed or remains unexplained.

Screening questions then turn to family history. For genetic arrhythmia syndromes, family history is critical to help establish the need for further testing and diagnosis. When assessing a child for inherited syndromes, take the time to perform a thorough and detailed family history. Simply put it can be lifesaving, not only for the patient, but for other family members as well.

Has any family member or relative died of heart problems or had an unexpected or unexplained sudden death before age 35 years (including drowning or unexplained car crash)? Has anyone in your family had a pacemaker or an implanted defibrillator before age 35?

These questions are attempting to tease out the possibility of acquired heart disease or coronary artery disease by using an age cut-off of 35 years. Coronary artery disease due to atherosclerosis is such a common problem in older persons and relatively uncommon below 35. This is not to say that coronary artery disease cannot manifest before the age of 35 years; only that it is less common. Hence, a sudden or unexplained death in a relatively young person (<35) should lead to an extensive search for conditions such as HCM, abnormal coronary arteries, and channelopathies. Unexplained or unexpected sudden death should be further investigated to determine the circumstances around the event and the health condition of the deceased before the event. For example, a car accident occurring at 10 a.m. due to collision with a truck on the highway resulting in death of the passenger is very different from an individual driving alone at 10 a.m. who suddenly crosses lanes and suffers a head-on collision with a vehicle traveling the opposite direction with the latter suggesting a cardiac event while driving. Another example would a person who knew how to swim ending up drowning in a swimming pool. Family members who have required the need of a pacemaker or defibrillator below the age of 35 may be a sign of genetic arrhythmia syndromes. As most genetic syndromes are inherited in an autosomal dominant fashion, identification of the relationship to the patient and other potentially affected family members is also critical to the investigation. A family pedigree is created to assess family member risks and inheritance patterns during genetic counseling.

Does anyone in your family have a genetic heart problem such as hypertrophic cardiomyopathy, Marfan syndrome, arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, short QT syndrome, Brugada syndrome, or catecholaminergic polymorphic ventricular tachycardia?

Clearly this question is seeking to identify specific diagnoses in family members. It is important to use these terms and synonymous terms in obtaining a history. Many of these conditions by name are difficult to relate to the cardiac system for the average person. As such, they may recall that a family member has a condition but not necessarily relate that this is cardiac related. Additionally, describing some of the conditions can help patients provide a better history such as describing hypertrophic cardiomyopathy as a “thickened” heart. Sometimes understanding what form of work-up was pursued may help patients reveal conditions in family members that can lead the interviewer down the correct path toward diagnosis.

Turning to the physical examination, the examiner is encouraged to utilize a full examination for the detection of potential cardiac disease. While this has traditionally focused on auscultation, other signs of cardiac disease may be demonstrable on examination. Marfan syndrome or other connective tissue disorders that may result in aortic dissection have specific features that may aide in diagnosis. The revised Ghent nosology is used for Marfan Syndrome in combination of family history, aortic dilation, and ectopia lentis. A hyperactive precordium or presence of a thrill may be discovered by palpation of the chest and may signal the presence of structural heart disease. The murmur of aortic stenosis and hypertrophic cardiomyopathy is systolic. Use of diagnostic maneuvers while auscultating can help distinguish and are directly related to preload and afterload of the heart. Asking the patient to move from a standing to squatting position increases the preload that results in a louder murmur for aortic stenosis but softens the murmur for hypertrophic cardiomyopathy. A return to standing reduces the preload and increases the intensity of the murmur of hypertrophic cardiomyopathy while reducing the murmur for aortic stenosis. Similarly, Valsalva maneuver also reduces the preload and results in the same changes to murmur as standing.

Diagnostic testing

In the scenario presented, the patient and mother came to the office with an ECG in hand. For this section, the debate of the screening ECG will be briefly discussed. The screening ECG is controversial in the pediatric electrophysiology community sparking numerous, passionate debates and position papers. As mentioned in previous chapters, the ECG is an excellent tool for the evaluation of rhythm related disorders in symptomatic patients. It is not a first-choice test for the evaluation of structural heart disease. But the simplicity of obtaining and low cost, make it appealing for an initial evaluation. By definition, the screening ECG is performed in the asymptomatic patient without prior history or concern of familial or personal cardiac disease. For certain disease such as Wolff-Parkinson-White, the resting ECG is diagnostic while for others such as CPVT, it is of little to no use. Much has been written on the probability of sudden death prevention with the use of screening ECG versus history/physical alone. There is little debate on the increase of pretest probability and reliability of a combined approach.

The challenge is not at the level of the individual, but at the level of public health. Are screening ECGs the best method to determine the likelihood of sudden death in the young? Once completed, the ECG must be correctly interpreted that can raise some complexity. Further points of debate include who needs an ECG? Athletes? Nonathletes? School-aged children? Newborns? Should it be repeated? How often? Are screening ECGs the most cost-effective method? How does this impact communities with lower socioeconomic status? Could public health dollars be better spent to affect the overall health of the public? These questions and more spark intense debate on the subject. While debate continues among experts, the lack of consensus has led to a localized or regionalized approach to screening ECGs.

Action plan

A few words on the terminology of “cardiac clearance.” Clearance may imply that the cardiologist or electrophysiologist has determined that the patient may undergo a procedure or start a medication based on the cardiac evaluation. A more appropriate definition is that the cardiologist or electrophysiologist has evaluated the patient from a cardiac perspective and feels that the benefit of the procedure or medication outweighs the cardiovascular risk at this time. The term “clearance” may suggest the elimination of risk, but this is most certainly not the case.

ECG screening in the pediatric patient considering stimulant medications for attention deficit disorders has a complicated and controversial history that will briefly be reviewed. Initial case reports of adverse events related to long-term use of methylphenidate including acute myocardial infarction and cardiac arrest in two adolescents prompted concern with stimulant use and cardiovascular effects. The Food and Drug Administration’s (FDA) adverse event reporting system recorded 11 cases of sudden death among pediatric patients on methylphenidate from January 1992 to February 2005 prompting the agency to place a warning label on amphetamine mixed salts in August of 2005. The issue was further escalated by the FDA to a black-box warning in February 2006. In 2007, the FDA recommended that drug manufactures prepare patient medication guidelines and alert them of cardiovascular risk and sudden death in those with preexisting heart conditions. This was followed in 2008 by a recommendation for screening ECGs by the American Heart Association that was soon followed by a rebuttal by the American Academy of Pediatrics.

What has not been debated are the effects of stimulant medication, resulting in a mild increase in heart rate and blood pressure that are well-tolerated in the normal population. The concern relates to those medication-induced changes in a more vulnerable population, specifically those with underlying cardiac disease. To date, there have been no long-term, controlled studies evaluating the cardiovascular risk for patients with and without cardiovascular disease. This reverts to the discussion on appropriate screening methodology for asymptomatic cardiac disease and use of the ECG to properly weigh the risks and benefits of proposed change.

A few facts have been certain and receive general consensus: (1) Patients with known cardiac disease should be under the consultation and follow-up of a pediatric cardiologist before initiating stimulant and stimulant-like medications; (2) Patients with concerning history or physical examination findings suggestive of cardiac disease should undergo consultation with a pediatric cardiologist before initiating new medication or new activity; (3) Patients with concerns for cardiac arrhythmia or sudden arrhythmic death should undergo an ECG; (4) A resting ECG can be both diagnostic and nondiagnostic depending on the sudden cardiac death condition investigated; (5) ECG interpretation is a skill that must be developed and should never be left to current ECG machine interpretation alone.

What am I thinking? ( Continued)

Given the above information, I would ask the pediatrician to not just look at the ECG but also get a history and examination as described. I would also offer to review the ECG and ask them to send it to me via facsimile or other means.

If the ECG is completely normal in my opinion, I would pass that on and tell the pediatrician that this is a reassuring ECG. As long as the mother understands that there can be false negative ECGs (patient has a condition but the ECG looks normal), the child can be allowed to take ADHD medications.

If the ECG shows abnormal or borderline findings (nonspecific or questionable findings that do not clearly point to a certain condition yet are concerning), the patient needs to have an outpatient visit with a pediatric cardiologist before ADHD medications can be considered appropriate for him. The final decision whether to start medications may end up being a complex discussion between the cardiologist, pediatrician, and family to make sure that risks and benefits have been thoroughly weighed.