Sudden Cardiac Arrest in Healthy Young Adults
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Hello and welcome to our listeners around the world. You're listening to the JAMA Clinical Reviews Podcast. Thanks for being here. I'm Dr. David Simel, JAMA Associate Editor and Professor Emeritus of Medicine at the Durham Veterans Affairs Medical Center and Duke University. In this podcast, we will be discussing out-of-hospital cardiac arrest in apparently healthy young adults.

I'm joined today by Dr. Ziyang Sen, who is a professor of medicine in the Division of Cardiology at the University of California, San Francisco. Dr. Sen is the lead author of our narrative review on cardiac arrest in the February 20th, 2025 edition of JAMA.

Dr. Sen, thank you for joining us today. It's a pleasure to be here. Thank you for having me. Well, a discussion of out-of-hospital cardiac arrest can be complicated, so I'd like to address a few scenarios today.

Let's start with the generalist physician who is called by their patient and told that the patient's young, healthy adult son is hospitalized after a cardiac arrest at home. Your patient is likely going to want to know about their child's survival and what that will look like. What can you say about the neurological outcomes?

So the good news is that approximately 90% of cardiac arrest survivors in the young adult population are discharged with good neurological outcome as defined by a cerebral performance category scale of 1 to 2. Well, the reality is that most patients then are not going to survive their out-of-hospital arrest. What do autopsy studies tell us about their underlying causes?

Yeah, this is a very important point. Traditionally, persons who are resuscitated from cardiac arrest to hospitalization or ultimate cardiac arrest survivors have been thought to be the same as those who died out of the hospital or in the emergency department. And these have been presumed to be sudden cardiac deaths. It turns out these conditions are not quite the same.

For those who are resuscitated from cardiac arrest, these are generally seen by clinicians in the hospital, while those who die out of the hospital are generally in the jurisdiction of coroners and medical examiners. And these cases are not routinely or systematically investigated.

But what we do know from a handful of systematic studies is that autopsies demonstrate about 40% of cases have a non-cardiac cause. And this can range from anything from a colt overdose to a neurological condition or infection, for example.

While the remaining 60% are indeed cardiac causes, and the most frequent of those are coronary disease, approximately a quarter, and then sudden arrhythmic death syndrome, which is a condition where the heart is structurally normal with an otherwise negative autopsy, and then other structural cardiac conditions like hypertrophic cardiomyopathy or dilated cardiomyopathy are other cardiac causes.

So coronary disease can be the cause in a large percentage of these healthy young adults. I guess I should have asked, what age range are we talking about when we say young adults? Yeah, good question. Generally, it's thought someone under the age of 40 is considered the young adult population.

Suppose the patient's child has survived and you're now the hospital medicine physician caring for the patient who's come off the intensive care unit. How do you and your cardiology consultant approach an evaluation to figure out what happened?

Yes, this is a good question. I will stress that upon initial resuscitation, it's important to have a broad differential diagnosis. And you start with a cardiogram after return of spontaneous circulation. After the patient is stabilized, imaging should be performed to rule out other structural causes, such as dissections. Neurologic imaging as well should be performed to rule out neurologic catastrophes. And then, obviously, a complete

workup including laboratory tests should be performed to rule out conditions like hypokalemia or hypomagnesemia that might be reversible. Another very important consideration is a drug screen, a toxicology screen, both for illicit drugs which are more common in this population as well as supplements including QT prolonging supplements because these are considered to be reversible conditions.

But once those things are ruled out, then you go down the path of considering all cardiac causes. And you start with an echocardiogram to examine for any structural conditions, such as a latent cardiomyopathy or mitral valve prolapse, for example. And then if those are ruled out, then you consider electrical conditions that might predispose someone to cardiac arrest. And the most common of these are long QT syndrome,

or Wolff-Parkinson-White syndrome. And then other electrical conditions that might predispose are Rougada syndrome, and then arrhythmogenic right ventricular cardiomyopathy is another one. Well, there's a lot to pack in there, so I'd like to explore a few of those things. You initially mentioned imaging. Were you talking about chest CT imaging to rule out dissection or disease of the greater vessels?

Yes, I think the first imaging that should be performed is a chest CT. Again, at this point, your differential is broad where you consider conditions like pericardial tamponade, aortic dissection, or hemorrhage. So a head-to-pelvis CT for intracranial or chest-pelvis emergencies is first.

And then the echocardiogram can be done pretty quickly if it's a transthoracic echocardiogram. Is a transthoracic echocardiogram all that's needed or is a transesophageal echocardiogram also suggested? The transthoracic echocardiogram is enough in the vast majority of situations to examine for dilated cardiomyopathy, for example, or hypertrophic cardiomyopathy, or certain valvular conditions.

However, other valvular conditions, such as mitral valve prolapse, may require a detailed examination with a transesophageal echocardiogram, but those are in specialized cases. And then for electrocardiographic monitoring, is the monitoring we typically do from the bed to a central unit okay, or are you talking about wearing an ambulatory monitor while they're in the hospital?

I believe it's essential to have continuous monitoring after a cardiac arrest for the simple reason that cardiac arrest is very high likelihood and high risk to recur during hospitalization. During monitoring, you may pick up dynamic QT intervals, non-sustained ventricular tachycardia, or other arrhythmias such as reentrant tachycardias that are predisposed in WPW. So continuous monitoring is essential. What about genetic testing?

Yes, so genetic testing is advised in cardiac arrest survivors in whom a phenotype has been established. So it's very important to first establish the phenotype so that you know what you're looking for in genetic testing. And so in genetic testing in this population, the range of positive yield is approximately 13 to 34%.

Again, it's important to emphasize that this is after careful phenotype assessment has been established in the population. So the genetic testing is done on whole blood, I assume? Yes, whole blood is generally the sample that is obtained. However, recent studies have also used things like buccal swabs, which are easier to obtain. And how is that actually ordered? I mean, what is the process for getting genetic testing?

So generally in the hospital, many centers may have a genetic testing consultation service where either a cardiac genetic testing service comes or a genetic counselor actually comes to meet with the patient and their family and then orders specialized genetic testing, including a panel of genes that include electrical conditions and structural conditions. Of those things that you can pick up by genetic testing, which would be the most frequent?

So the most frequent conditions are dilated cardiomyopathy, hypertrophic cardiomyopathy, and then electrical conditions like long QT syndrome and Brugada syndrome. Arrhythmogenic right ventricular dysplasia is another condition that's relatively common in this population. And then each of those have a specific genetic marker.

That's correct, including several genes that have been published in association, and it must be noted that that panel continues to expand as we learn more and more about the genetic underpinnings of these conditions. Well, let's suppose you're the electrophysiologist who is asked about prevention and implantable defibrillators. Are defibrillators recommended for most survivors of out-of-hospital cardiac arrest who do not have reversible causes?

That's right. So sudden cardiac arrest survivors in whom non-cardiac or reversible causes are excluded remain at high risk for recurrent ventricular arrhythmias. So based upon landmark trials now 20 to 30 years ago, ICD implantation as secondary prevention is indicated for these patients.

Now, in the young adult population, there's an initial consideration as electrophysiologists for what type of defibrillator is appropriate. And in recent years, an alternative to the conventional ICD is the subcutaneous ICD, where the lead is not tunneled through the blood vessels, but is instead tunneled subcutaneously. What is life like for a person wearing a defibrillator?

So a defibrillator does require certain lifestyle considerations and changes, and it depends on the type of defibrillator. It is certainly under the skin, but there are certain things like contact sports that may be not advisable for risk of damaging the defibrillator. There are also for transvenous leads, transvenous wires, there are certain activities that I recommend patients avoid,

to prevent damage to the leads, such as repetitive rowing machine type of exercises.

Well, you brought up the athlete, and that's a great segue to what I'd like to explore next. And that is, how do you decide the safety of returning to competition when the out-of-hospital arrest occurred during athletic activities? So the incidence of sudden cardiac death among young athletes is actually quite low on the order of 1 in 100,000 young athletes per year. And this is notably about one-tenth of the rate in older adults.

Now, in recent years, paternalistic guidance has been changed to more of a shared decision making in which the athlete participates in the discussion. Patients, however, with unusual or high-risk features such as syncope, especially during exertion, we might consider more restriction in that population. But for most other individuals, the overall benefits of exercise outweigh the risks.

So the way I think about it in people who do have a condition that's identified that's high risk, such as a structural or rhythmic condition, there are three types of activities that I generally recommend against.

And those are activities that are sort of burst exertion where somebody does rapid acceleration or deceleration and sprinting, such as basketball or soccer. Those activities that have more stable activity energy expenditure like jogging or biking, lap swimming, those are more preferred activities.

The other situation would be extreme environmental conditions like altitude or extremes of temperature. Those can affect electrolytes and blood volume, and that should also be avoided. And then lastly, I would avoid progressive training loads where the goal is to achieve higher and higher performance. Those are to be avoided as well. How would weightlifting be considered?

Weight lifting, I think in moderation is okay, but it goes under the category in my mind of if the goal is for progressive training for more and more performance and more and more weight lifting, I think I would avoid that. But if it is to maintain good cardiovascular condition and exercise, I think that would be okay. Well, let's get back to the clinic where your patient might ask about the risk in their other children. Are there

prescribed set of tests that you would recommend for the first degree siblings of a survivor or someone who has not survived?

Yes, this is a great question. So the theme here is to establish a cause, I think. That's the most important. If the cause or the phenotype in a resuscitated case is established, then recent expert consensus statements recommend genetic testing focused on the potential candidate genes of that condition and a clinical evaluation of family members to identify relatives who have or are at risk of developing the same condition.

Now, if the cause is not determined, first-degree relatives, it's still recommended to undergo a clinical evaluation, including an ECG, cardiac imaging, ambulatory monitoring, and potentially provocative electrical testing. And so that's how I think about screening in family members of persons resuscitated. Well, let's think about the person who has no family history whatsoever and is a young person about to go to school and participate in competitive athletics.

Could you talk a little bit about the considerations and maybe the controversies in screening the asymptomatic person with no family history? Yes. As you alluded to, the approach in the United States is different than that in Europe in the

The last two decades, pre-participation screening, for example, for early identifications of conditions at risk in high school, college, and professional settings has been examined. In the U.S., this approach is limited to history and physical examination, while in Europe, it

particularly in Italy. ECG is routinely employed as part of this process. And actually, a study was performed and it found a comparable incidence of cardiovascular deaths in both areas. So in the U.S., pre-participation screening is limited to the comprehensive history taking and physical examination and does not recommend routine ECG screening in a general population. Due to concerns for diagnostic accuracy, cost-effectiveness, and availability of physicians in a

However, of course, if a particular condition is identified, then ECG or transdothoracic echocardiogram should be performed in those select individuals. Again, this differs from the recommendation in the European Society of Cardiology Guidelines, which do recommend a 12-lead ECG for all persons in competition younger than 35 years old.

Are there any other things you would like our listeners to understand about out-of-hospital cardiac arrests in young, healthy adults? Well, I often take a step back and remember these are catastrophic life events that have substantial negative effects on patients and their family members. So psychological evaluation and treatment of grief and post-traumatic stress in survivors and their family members is important. Remember to take care of their mental health as well.

Thank you, Dr. Sen, for joining us today to talk about out-of-hospital cardiac arrests in healthy young adults. I am Dr. David Simel. You can find a link to the article in this episode's description. This episode was produced by Shelley Steffens at the JAMA Network.

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