Case

Thank you for taking my call. I am a local pediatrician and I just had a mother come in with her son for an evaluation. He is an 11-year old young man who I have been following since birth and has no real medical history to speak about. But the reason I am calling you is that the mother informed me today that his father had passed, suddenly, 2 weeks ago, at the age of forty. According to mom, the father had no previous medical history and so all of this is a complete shock. The family is saying he had some kind of “heart attack” but he never had any cardiac history prior and from what I saw of him, he was fit and healthy. Someone from the family has a background in medicine and suggested that the child be evaluated for the risk of sudden death. The mother is obviously devastated and fearful for her son’s life. I’m wondering if there is anything special, I should be doing?

What am I thinking?

It is always difficult to manage the sudden loss of a family member. There is a balance in affording the family the appropriate time to grieve while ensuring that the appropriate actions be taken to provide much needed answers to this tragedy. Given the sudden nature of the death and the relatively young age of the parent, it raises concerns about the potential for an inherited cardiomyopathy or arrhythmic syndrome that may put first-degree relatives at risk. Any details surrounding the father’s medical history or symptomatology will be important to elicit as well as the circumstances around the death. It will also be important to determine if an autopsy was performed or if this was a coroner’s case that may also help provide clues as to the condition that led to the sudden death. Finally, obtaining blood samples from the deceased, which must be preserved in a purple top tube and can be frozen for future genetic testing can be critical for further diagnostic testing of family members. These conversations are difficult with grieving family members but many times, they can help to determine appropriate next steps and help provide some answers to the ultimate question of “ why did this happen ? ”.

History and physical

Any child with a first-degree relative who suffers a sudden unexplained death before the age of 35 (some publications consider before the age of 50) with possible cardiac origin should be evaluated by a pediatric cardiologist. As part of that evaluation, a thorough cardiac history of the child should be obtained to determine if there are any signs and/or symptoms suggestive of cardiac disease. A physical examination should also be completed with attention to any pathologic murmurs.

Next, the history must turn to the family member who suffered a sudden cardiac arrest. This can be a very painful time for the family and questions should be asked with the utmost level of sensitivity to the situation. It is important to ascertain the prior health of the deceased, specifically asking about diagnosed medical conditions, medications taken, and unexplained syncopal or seizure events. Directly ask about any known cardiac conditions or concerns throughout life. If the deceased is an adult, it may be helpful to gain childhood information from the parent of the deceased. Finally, obtain details around the circumstances of the death event. How was the victim feeling that day? Were there any complaints or symptoms expressed? Were there any unusual activities performed? Were there any unusual environmental conditions that could have led to the death event (i.e., driving late at night, swimming, extreme sports, etc.)? Was the event witnessed? If so, are there details that can be provided? Given the emotional nature of these questions, it is critical to provide the family the appropriate amount of time to gather thoughts, express their feelings, and calmly work through the process.

Next, we turn to family history and the development of a family pedigree. Information should be solicited from knowledgeable family members regarding siblings, parents, grandparents, and other relatives who may have suffered from similarly tragic circumstances. Of note, this may need to take place over several visits or taking the time to allow family members to call each other to sort out the medical history as you ask questions. It is not uncommon to be in an office visit while on the phone with a family member across the country who is answering questions about estranged relatives.

Frankly speaking, none of these important questions and clinical investigation can be accomplished in a 30-minute visit. The appropriate amount of time must be allocated and may require a spread over multiple visits and with multiple family members. The opportunity must not be taken lightly as discovering the nature of the event and what may have led to it will help provide a plan for further testing and evaluation of all first-degree relatives for inheritable conditions.

Diagnostic testing

An ECG and echocardiogram are reasonable tests to order on a first degree relative of a presumed victim of sudden unexplained cardiac death at a young age. The focus of the ECG is to review for electrical conditions that may suggest an arrhythmic related death, while the focus of the echocardiogram is to look for structural heart disease. If the deceased family member has a history of an ECG or echocardiogram previously performed, this would be beneficial for review. If physical activity was related to the circumstances of the death, it may be worth pursuing an exercise stress test. Other testing that a pediatric electrophysiologist may employ could include a medication challenge, Holter or other forms of ambulatory ECG monitoring, cardiac MRI, signal-averaged ECG, or diagnostic electrophysiology study depending on the suspected condition.

Genetic testing revealing a known mutation for a specified disease is becoming the standard for diagnosis. A coordinated effort between the local medical examiner and those investigating for sudden cardiac death can help ensure that genetic material is made available for testing. It is recommended to keep 5–10 mL of whole blood in EDTA containing tubes (purple top) that can be frozen. If blood is not available, cardiac or any body tissue can be used for genetic testing. Given that such requests are by definition unexpected, the wise cardiologist has preemptively educated the local emergency rooms, medical examiners and the like about this issue so that they have an actionable plan when dealing with a sudden unexplained death, particularly in the young. A positive genetic test in a deceased family member for a known mutation specific to a disease state can help provide the most appropriate testing for other family members to identify those at risk. However, genetic testing can also demonstrate variants of unknown significance. These are identified mutations that are not known to be disease-causing but may be consistent within a specified region of the genetic sequence that can contain known disease-causing mutations. These mutations should be reviewed with the help of a genetic counselor and pediatric cardiologist specializing in genetic arrhythmia or structural cardiac disease.

Action plan

The suspicion for cardiac-related sudden death is high for the patient in the scenario. A pediatric cardiology consultation should be performed with emphasis on history taking and a clear understanding of the potential conditions the deceased family member may have had before the event. Family history should be thoroughly reviewed and may require further conversation with family members outside the immediate family while documenting a family pedigree. All first-degree relatives of the decedent should be screened. An ECG and echocardiogram are usually an acceptable place to start for evaluation of cardiac disease, but further testing may be required depending on the suspected differential. Due to the time-sensitive nature of genetic testing, an early conversation should be held with the medical examiner or coroner to review the need for two 5–10 mL EDTA purple top lab tubes of blood that can be frozen for future genetic testing. Once the sample has been confirmed obtained, further discussions into the pros and cons of genetic testing can be held with the family, preferably with a genetic counselor, including its limitations and associated costs. In the scenario of no demonstrable diagnosis with genetic testing, DNA can be banked by various institutions for future testing should the need arise.