Troponin After Cardiac Surgery; Doctor-Prescribed Exercise; COVID False Negatives

TTHealthWatch is a weekly podcast from Texas Tech. In it, Elizabeth Tracey, director of electronic media for Johns Hopkins Medicine in Baltimore, and Rick Lange, MD, president of the Texas Tech University Health Sciences Center in El Paso, look at the top medical stories of the week.

This week’s topics include false negatives with COVID testing, troponin after cardiac surgery, physician-prescribed physical activity, and a monoclonal for RSV infection prevention.

Program notes:

0:33 Lateral flow assays in COVID testing

1:34 Not as reliable at excluding disease

2:34 Need further development and validation?

3:37 Primary care prescribed exercise

4:35 A little bit better with self report or a device

5:35 75 to 100 minutes of vigorous activity

6:25 Troponin after cardiac surgery

7:25 Do the biomarkers predict poor outcomes?

8:25 Comorbidity impact?

8:40 A monoclonal antibody for RSV

9:40 Efficacy between 60 and 70%

10:31 Prevent infection in term infants

11:20 Use prior to RSV season

12:21 End

Transcript:

Elizabeth Tracey: Does it help if a doctor tells you to exercise?

Rick Lange, MD: Detecting a heart injury after cardiac surgery.

Elizabeth: A monoclonal antibody for respiratory syncytial virus.

Rick: And use of home COVID testing for detecting COVID infection.

Elizabeth: That’s what we’re talking about this week on TT HealthWatch, your weekly look at the medical headlines from Texas Tech University Health Sciences Center in El Paso. I’m Elizabeth Tracey, a Baltimore-based medical journalist.

Rick: And I’m Rick Lange, president of Texas Tech University Health Sciences Center in El Paso, where I’m also the dean of the Paul L. Foster School of Medicine.

Elizabeth: Rick, how about we turn, of course, to the COVID material first — the only study actually this week we’re talking about from COVID. It’s all yours from the BMJ.

Rick: Let’s talk about what I served up as home COVID testing, but it can also be done in a commercial setting. It’s using what are called COVID antigen lateral flow tests. These particular tests are what’s distributed to individuals to test at home because they are fairly inexpensive, they’re easy to do, and it gives instant results. How valuable are they assessing presence of infection in people that don’t have any symptoms?

What they did, this was a study conducted in the U.K., is they used lateral flow testing in a variety of different settings: various centers around the country, sometimes symptomatic, sometimes asymptomatic, residents that did not have symptoms, and they were having municipal mass testing centers in Liverpool and students without symptoms that were being tested at the University of Birmingham. All in all, there were about two and a half million individuals that were either being tested or had contact with individuals who were COVID-positive.

Here is what they discovered. The tests aren’t as reliable in excluding disease as we would like them to be. If someone had a viral culture positive result — so we know they have infection, but they didn’t have symptoms — this lateral flow testing would miss about 20% of those done at what are called the trace settings, about 30% of individuals without symptoms, and about 81% of those individuals who were actually at the university.

Somewhere between 20% and 80% of the tests would be false negatives. Unfortunately, I think a lot of us put a lot of stock in it. If it’s negative, even if you have symptoms, “Gosh, it means I don’t have COVID.” What this would suggest is you really can’t take it to the bank if it’s negative. If it’s positive, it’s likely a true positive. If it’s negative, not so much.

Elizabeth: OK, this is a pretty pathetic result and frankly I’m really sorry to hear it in some respects, because it blows away any sense of security I may have had. Of course, this is the same technology that’s used in pregnancy tests, and they are extremely accurate. So is this a matter of just the need for further development and validation of these tools? Or is this collection of the specimen? Or how do we account for the fact that they are just turning in this really pathetic data?

Rick: Well, Elizabeth, probably all of those things have a role in it, but really the most important thing is the testing. This tests the antigen, not the genetic material — that’s with the PCR test. The PCR test is much more sensitive. One has to have a lot higher viral load detected here.

We used to think, “Well, gosh, if you didn’t have enough of that viral load, you really weren’t infectious,” but that’s not the case. I think we put too much emphasis on using this to rule out disease, especially in asymptomatic people, and especially in kids, by the way.

Elizabeth: All right. Well, I’m going to put you on the spot just a little further here and say for right now, then when people are interested in being tested, what would you suggest?

Rick: You can use these tests. If it’s positive, I think it definitely is an accurate test. If it’s negative, though, and you’re still concerned, then I think it needs to be followed up with a PCR test. We don’t have any good testing — if someone’s just going to be routinely testing two or three or four times a week and they’re asymptomatic, I think that’s a waste of time. That’s a waste of effort and that’s a waste of money as well.

Elizabeth: Sticking with the BMJ, let’s take a look at a study that says, “Gosh, if we have primary care docs actually advising people to exercise more, does this really help?”

This is a meta-analysis. They used an acronym — MVPA — for moderate-to-vigorous-intensity physical activity, and that was their measure. They attempted to look at randomized controlled trials of aerobic-based physical activity interventions that were delivered or prompted by health professionals in primary care.

They ended up with 14,500 + unique reports and 46 randomized controlled trials with a range of follow-ups between 3 and 60 months. Their number of participants were just over 16,000.

This MVPA was only increased by about 14 minutes per week if it was prompted by a primary care health professional. It was a little bit better than that if it was, first of all, a self-report, and secondly, if some device was also employed during that time. The authors point out that just 14 minutes actually could be quite impactful with regard to reducing cardiovascular disease risk, and so maybe that’s true. But 14 minutes sure doesn’t sound like a lot to me, and I am wondering how long it takes the healthcare professional to advocate for this in order to get even that really very small change.

Rick: I agree. This could be a “half glass full” or “half glass empty” results of the study. That 14 minutes per week extra moderate-to-vigorous physical activity actually translates into an 11% decrease in overall mortality. On the one hand, 14 minutes doesn’t sound like much. On other hand, 11% reduction in overall mortality is pretty substantial, especially when less than one-quarter of the individuals in the United States actually get enough exercise to meet the guidelines. That is somewhere between 150 to 300 minutes of moderate-intensity physical activity or 75 to 150 minutes of vigorous physical activity.

In fact, just the primary care physician’s intervention increased the number of individuals — or the percentage of individuals — meeting those guidelines by 33%. About 80% of people see a primary care physician every year. The more often they get touched, the more likely that they are to follow the activity recommendations. So modest, but significant? Yes.

Elizabeth: OK. Then I would like you to comment, though, on the burden that’s placed on that visit by having to cover also one’s physical activity in addition to the multitude of other things that primary care docs are responsible for.

Rick: Yeah, and we have a short amount of time. We try to encourage individuals to assess what’s going on. But I would say it’s a pretty big bang for your buck.

Elizabeth: On that note, let’s turn to the New England Journal of Medicine, this ongoing issue of troponin [and] cardiac health, and this, of course, a specialized population.

Rick: Elizabeth, there are over a million patients that undergo heart surgery in the United States and Europe annually. That heart surgery is obviously to address symptoms or improve survival in patients that have coronary artery disease or need a valve surgery or some other type of heart surgery. But it also carries some risk with it as well. Sometimes the surgery itself can cause myocardial injury, or actually a myocardial infarction. We would like to be able to assess that.

How do we typically do that? Well, following surgery, people have chest pain because they just had surgery. They oftentimes have EKG changes, so we rely upon biomarkers. In the past, we said, “Gosh, depending upon the guidelines, if the cardiac biomarkers are 10 times the upper limits of normal, or 35 or 70 times the higher level, that would indicate myocardial injury.”

Here is what they did with this study. They said, “Let’s really assess whether that’s true or not.” Did those levels of increased biomarkers actually predict who will do poorly or not? They studied just short of 14,000 patients in this international prospective study.

And fortunately, very few died in the first 30 days, only about 2.1%. Then when they looked at the cardiac biomarkers that predict who is more likely to die after surgery, it was an increase between about 300 to 500 times the normal values. The vast majority of individuals after surgery — just as a result of the surgery — will have that modest increase that was previously thought to be predictive. What this study says is the current guidelines that we are following really don’t predict who has had significant myocardial injury or infarction that’s going to affect their mortality after cardiac surgery.

Elizabeth: OK, how do these guidelines need to be modified then?

Rick: We need to throw away those old numbers and use higher numbers. Unfortunately, the study doesn’t tell us what the source of the injury is. Once we know what the numbers are, then we could begin to look at what causes it and then to see what we can do to intervene.

Elizabeth: I guess I am also wondering about comorbidities and how they might impact this.

Rick: That’s really interesting because this study corrected for all the comorbidities. What does the cardiac biomarker add to that? That’s why this study and the information it provides is so important.

Elizabeth: A moving target, no doubt. Let’s also stay in the New England Journal of Medicine. Last week we also talked about respiratory syncytial virus, or RSV, and now we are talking about it again. This time we are talking about it because there’s a monoclonal antibody called nirsevimab.

In this study, they gave it to healthy late preterm and term infants to see whether it was capable of preventing RSV infection. They had 1,490 infants who underwent randomization, two-thirds of which were assigned to the nirsevimab group and about 500 to the placebo group. Their outcome measure was medically attended RSV-associated lower respiratory tract infection, and that occurred in 1.2% of the monoclonal antibody group and in 5% of the placebo group. That’s pretty good efficacy of almost 75%.

They also looked at hospitalization for these infections. That occurred in only six infants in the monoclonal antibody group and in eight of them in the placebo group. The efficacy was 62%.

This looks pretty good. They also looked at what were the side effects of having this infusion and they really didn’t see anything that was substantially different between the placebo group and the monoclonal antibody group. What they conclude is that this really does help. I guess I have a lot of questions about implementing this thing clinically. What are your thoughts?

Rick: We have talked about RSV prevention in premature infants and in those that have underlying heart and lung disease, because those are the ones if they get an RSV infection are likely to develop severe respiratory problems and likely to be hospitalized and/or die.

But when you look at things in the totality, there are more normal kids. When they get infected, there is a higher number of them they get hospitalized just because there’s more of them around. Now we have turned our attention to say, “OK, if you’re not preterm and don’t have lung or heart disease, can we prevent infection and will this antibody do it?” And it does.

The nice thing about it is it’s a single injection. The injection lasts for at least a half a year and as long as up to a year in terms of prevention. To me, it seems like it’s a pretty easy thing to do.

Elizabeth: I’m just really interested in how this is going to be operationalized. It seems to me that there is already so much stuff that one has to do for a newborn. I am just wondering how this is going to fit into that whole armamentarium of things that are already employed.

Rick: Yep. Shortly after birth these babies have well-baby examinations. We don’t normally start giving injections to them until months to years afterwards because they have maternal antibodies. But this is a case where you would give it prior to RSV season, depending upon whether you’re northern or southern hemispheres. To me, I think it’s pretty easy to administer.

Elizabeth: You might pooh-pooh this, but I still think we don’t know yet. What are the long-term implications of the administration of exogenous monoclonal antibodies?

Rick: Well, you’re right. They measured antibodies to their antibodies.

Elizabeth: Yes.

Rick: It occurred in about 6% of the kids. There weren’t a long-term sequelae, but the sequelae they were looking at were a relatively short period of time. That’s a good point.

Elizabeth: I guess the other thing that’s not covered in this study is, what’s this going to cost?

Rick: You’re right. This doesn’t provide a cost-benefit analysis. What you’d like to know is that at a societal level, the cost of administering it is lower than the cost associated with all the hospitalizations because these are otherwise normal kids. I agree with you, it would be nice to follow this up with a cost-benefit analysis.

Elizabeth: On that note, that is look at this week’s medical headlines from Texas Tech. I’m Elizabeth Tracey.

Rick: And I’m Rick Lange. Y’all listen up and make healthy choices.