One of the possible etiology could be Brugada syndrome or Long QT syndrome. 

ECG, Holter , Electrophysiology study , Ajmalin provocation testing and genetic testing may be the battery of test to dignose the cause. Depending upon the cause and its reversibility; children should be advised for sports life.

Dear Shankar, the father suffered sudden cardiac death with apparently normal heart.

The first question is: do you trust the pathologist? Many general pathologist only look at coronary arteries but easily miss cardiomyopathies if they are not used to seeing those.

If you do trust the pathologist, than the second question is: do you have an ECG of the subject who died? It is very rare that a patient with a ion channel disease and a normal or borderline ECG dies suddenly. For example it is true that some patients with Brugada syndrome may have a normal baseline ECG and only sodium channel blocker test reveals a coved-type ECG. But these individuals have a very low risk of SCD. Also long QT syndrome: some genotype positive individuals have only borderline prolonged QT interval, but again the risk is low and it is unlikely that they die suddenly. Finally, look at diffuse early repolarization with prominent J-waves.

So if at the end you did not find anything and thus you made a diagnosis of "idiopathic VF", according to our experience (which is honestly very good in the field) and the literature, the risk of family recurrence is very low (I don't know of a single case published in the literature). Also consider that, with few exceptions, the risk of sudden death is very very low before pubertal development so at the age of 10 and 7 I would only do an ECG and an echo, not certainly invasive test like EP study that in my opinion is not justified. When they will be grown up, say at the age of 16, I would perform a cardiac MRI: but I am sure in 6 years time we will know much more about it. Genetic testing is a chance, but I would have done it to the dead person first, and extend to family members only if something is found. 

I hope this has been useful.

Kind regards

Alessandro

 Dear Dr Alessandro Zorzi,

Thanks for the approach. Do I trust the pathologist? I am not too sure about that aspect. The autopsy was done at a district hospital, mainly from the medico legal angle. The medico legal pathologists look at the body with a different perspective. So, the possibility of some oversight does exist.

I will try to retrieve the ECG done about 2 months ago on the individual. Though reported as normal then, It is worth a relook for subtle changes as you mention. Reassuring to know about the low risk in the children.

What about the risk in siblings? What screening protocol is advocated for the 3 siblings (all male) aged 48,46 and 40. 

regards

Dear Hemant,

Thanks for the valuable inputs

regards

The points raised are valid, and you need to rule out the obvious, but I would disagree the the risk is low. Why did this gentleman die on that day and not 1 day/month/year previously. It is the deadly combination of age, sex, hormonal/metabolic/ionic levels, heart rate, acquired heart disease, etc. that all come together to establish the substrate for arrhythmias. 

There are patients LQTS genotype positive without QTc prolongation, yet they unfortunately undergo cardiac events. Also, LQTS male patients are at a higher risk of cardiac arrhythmias before puberty, and the risk rather decreases after puberty. Yet, the risk differs in female patients. There is a lengthy body of literature on this topic.

First of all it is careful family history  SD and syncope in father and family, relatives.Another time circumstances of SD of father comlaines, is it possibly postmorten genetic  test first of all for LQT1, Brugada syndrome.  Family ECG

For sons:

1)history syncope, weakness during, after exercise, palpitation

2) Physical examination, murmur, heart size, blood pressure

3) 12 lead ECG orto-clinoposition (HR, QTc, axis of the herart, ST deviation, E- wave)  ECG in high intercostal leads for possible signs Brugada syndrome, Late potentials 

3)Holter monitoring (heart rate (min-ma[), arrhythmias, T wave alternanse, HRV, QT dymanics

4)Stress test (bycilcly or tredban) arrhythmias> T wave alternanse, ST changes< QT interval

5)EChoCG - structural changes, cavity size,

If you not find any sings heart diseases, arrhythmias, chanalaopathies you could allow for children any physical activity but with regular control (1 time in year) ECG, EchoGC, Holter. 

Best regards

Leonid

Dear Dr David S Auerbach,

Thanks for the valid comments. Would appreciate the relevant literature, if possible.

regards

Dear Dr Leonid Makarov ,

Thank you for the inputs

regards

Not all sudden deaths are due to cardiac causes, in the same way that not all sudden cardiac deaths are due to changes in the QT-interval.

A study of brain structure was conducted at autopsy? to take an example.

Dear Dr Francisco R Breijo-Márquez,

That's an interesting thought. I don't think the brain structure was reviewed. The individual ran 8 Km, got down from the treadmill, sat on the ground for a few seconds, then lied down. He got up again after half a minute of so, mumbled something and then lied down. The event was witnessed by 2 people who did not know about CPR, so they did nothing except call for help. Help arrived in 3-4 minutes and confirmed a cardiac arrest. By that time pupils were already dilated and fixed.

With this degree of suddenness, the whole focus was indeed on the heart. The autopsy was done at the district hospital and the chest and abdomen were explored. I don't think the skull was opened.

Neurological emergencies usually give a little bit more time than a few minutes like in this case. Also, epidemiologically speaking, cardiac causes do significantly outnumber other causes by factor of almost 80-90:1. Also, the preceding history of running shifted the focus entirely on the heart.

What alternative would you suggest and how would it affect the screening protocols for the siblings and children

regards

I agree with Dr. Shankar

No single test to be advised but a detailed history from the sons should be taken (any palpitations/ dyspnea/ lightheadedness/ presyncope or syncope), 12 lead ECG and Echocardiography. if all ok, they should be seen regularly every 1-2 year till age of 18 with ECG and Echo.

It would be very helpful if a gentic testing was done on the victim to extend it to his relatives.

P.S.Dear Shankar if you have possibility to perform panel of genetic testing for children of diea father, more perspecive in this row - LQT1, LQT2, S Brugada and Ryanodin Receptor for CPVT, may be HGMP (Behr et al)

Thank you Dr Alshaika and Dr Makarov