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In This Week’s Podcast
For the week ending June 11, 2021, John Mandrola, MD comments on the following news and features stories.
I had a great vacation. Staci and I backpacked over 100 miles on the Appalachian Trail in western North Carolina and Virginia. I met up with a bear, slept with a few mice, and observed a distinctly curious form of human being called through-hikers. Yes, people actually walk the entire 2100-mile trail from Georgia to Maine. I made many memories.
COVID and COVID Vaccines
The COVID tide has turned in the last few weeks, with plummeting cases and deaths. We saw no almost no masks in NC and Virginia. On TV, I saw a Stanley Cup hockey game with a huge indoor crowd, as if there was no pandemic. The Indianapolis 500 welcomed 135,000 fans on Memorial Day weekend. Normalcy is around the corner, and this is great news, surely due in large part to the COVID vaccines.
Speaking of COVID vaccines, though, there is a cardiac issue to discuss. The journal Pediatrics has published a case series of 7 young boys who developed symptomatic acute myocarditis following the Pfizer vaccine. The thing I find most remarkable is the clear-cut nature of the cases—unlike many of the COVID-myocarditis-reports, which mostly stemmed from abnormal cardiac magnetic resonance (CMR) scans, the pediatric vaccination cases had huge elevations of troponins, CRPs, and abnormal CMR scans. These kids surely had significant cardiac injury. The authors of the report stated that they were not making a causal relationship between the vaccine and the myocarditis.
But there have also been reports from other sources: The acting health commissioner in Connecticut has announced “at least 18 teens and young adults have shown symptoms of heart problems after receiving the vaccine.” On June 1, Science published coverage of a report from Israel that concluded, provocatively, that between 1 in 3000 and 1 in 6000 men ages 16 to 24 who received the vaccine developed myocarditis.
The European Medicines Agency (EMA) has made note of the issue and has requested more information and will consider whether any other regulatory action is needed. And yesterday, during a report to the US Food and Drug Administration (FDA), Dr. Tom Shimabukuro of the Center for Disease Control and Prevention (CDC) Immunization Safety Office reported that the agency has received reports of 275 cases in the 16 to 24-year age group as of May 31. This exceeded the expected number of myocarditis cases by a lot. Shimabukuro said: “We clearly have an imbalance there.”
My comments on this are from the point of view of a neutral Martian who simply looks at the risk/benefit calculus and is not encumbered by the polarization and ideology surrounding COVID.
If there is a causal link here, which seems increasingly likely given the circumstantial evidence from multiple sources, the probability that a young person gets myocarditis after vaccination is very low, ranging from as a high as 1-in-3000 to as low as 1-in-100,000.
But in this age-group, the risk of suffering severe COVID is also in that very-low range. What’s more, at this moment, the community prevalence of COVID is super low.
Perhaps we should spend a few more months collecting data on vaccine adverse effects in this age group before issuing emergency approval. The calculus for young people is simply different from older adults.
Compare the reaction to this vaccine-linked event with the extreme angst many experts displayed for the potential for myocarditis after COVID infection. A handful of flawed studies almost stopped college sports. Recall that these purported cases of myocarditis were mostly just abnormal CMR scans in patients with mostly normal troponins and ECGs. Now we have a not tiny number of definite cases of cardiac injury among previously totally normal kids, and, yet I am not observing much concern out there in the media. Why is this? It’s peculiar.
I am just an electrophysiologist, but it appears to me that we have crushed COVID by simply vaccinating susceptible adults. Why not wait for more data before extending these novel therapies to young people?
AF Detection Post Stroke
JAMA published two RCTs looking at the detection of atrial fibrillation (AF) after stroke. The first trial, called STROKE-AF, asked the question of whether insertable cardiac monitors (ICM) will detect more AF in patients with a recent ischemic stroke attributed to large vessel or small vessel disease.
STROKE AF excluded patients with cryptogenic stroke, known cardioembolic stroke, or known AF. About 500 patients with stroke were randomly assigned to having an ICM or standard care. The primary outcome was AF for more than 30 seconds in the following year. Considering that patients were a mean age of 67 years, and had median CHADSVASC of 5.0, the results are predictable:
12% of the ICM group had AF detected vs 1.8% in the standard care group. The hazard ratio (HR) was 7.4 times higher for picking up AF.
Supplemental figure E1 showed that most AF was less than 6 hours in duration, about 25% lasted 6 to 24 hours, and less than 5% lasted more than 24 hours.
Most subclinical AF events occurred after 30 days, and anticoagulation therapy was prescribed for 18 of 27 patients (67%) in the ICM group who had subclinical AF.
The authors concluded that further research is needed to understand whether identifying AF in these patients is of clinical importance. Of note, Medtronic, the maker of the ICM, funded the study.
Also in JAMA, the Canadian PER DIEM RCT studied the use of ICM vs 30-day ECG monitoring after an ischemic stroke. The primary outcome was AF lasting at least 2 minutes during the first year. About 300 patients with ischemic stroke were randomly assigned to either the ICM or 30-day event recorder. Unlike STROKE AF, about two-thirds of patients in PER DIEM had a cryptogenic source.
PER DIEM reported similar results as STROKE AF—about 15% AF detection in the ICM group vs 5% in the external loop recorder group. This led the investigators to conclude that “further research is needed to compare clinical outcomes associated with these monitoring strategies and relative cost-effectiveness.” Medtronic provided the ICMs for this study but funding mostly came from grant support.
Cleary, the more you monitor older patients with high CHADSVASC scores, the more AF you will detect. These two trials confirm the 2014 trials done after cardioembolic stroke which also found that more monitoring led to more AF detection.
These studies may lead to more ICM sales. ICMs are quite costly, not only in the initial cost, but also the costs of repeating downloads, but I am not sure whether more ICMs will lead to fewer strokes.
Both sets of authors strongly stated that the major weakness of these studies was that AF is a surrogate and not a clinical outcome, and we need more research looking at how AF detection bears on reducing future stroke.
Consider the STROKE AF cohort. These are patients who presumably had ischemic stroke due to atherosclerotic disease in either a large or small cerebral vessel. Patients with cerebral atherosclerotic stroke benefit from antiplatelets and statins. Now you detect 6 minutes (or 6 hours) of AF months later. Do you add oral anticoagulants (AC) to a regimen of antiplatelet drugs? This will surely reduce thrombotic risk, but will the increased bleeding from taking two clot-blocking drugs nullify the benefit?
The editorialists note that most treating neurologists started oral AC when AF was detected. I totally get this when the stroke is clearly cardioembolic, but I think it’s highly presumptuous when stroke was due to atherosclerotic origins—say in a lacunar stroke.
One of the major questions for modern cardiologists will be the threshold of AF burden that renders oral AC a net benefit. Answering this question will require more than just data from an ICM; it will also require consideration of the unique characteristics of the patient.
Fortunately, two ongoing outcome RCTS are looking at direct-acting oral AC use in patients with device-detected sub-clinical AF. But in post-stroke patients I think we need a heck a lot more outcome trials. Recall that NAVIGATE ESUS and RESPECT ESUS found that empiric novel oral AC after embolic stroke of undetermined source (ESUS) did not reduce stroke vs aspirin.
I see a lot equipoise in the treatment of subclinical AF. We’ve never had this much monitoring capability, so we don’t know the “normal” baseline amount of AF that older patients have. Secondary prevention of stroke is a super common intervention. Rather than guessing, it would be much wiser to enroll these patients in clinical trials.
This week, the FDA approved a 2.4 mg/week subcutaneous dose of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide as an adjunct to a reduced-calorie diet and increased physical activity to treat adults who have obesity (body mass index [BMI] at least 30 kg/m2) or are overweight (BMI at least 27 kg/m2) with at least one weight-related comorbidity.
Approval was based on the four phase 3 STEP trials, which I discussed on the Feb 26th podcast. In the STEP I trial, semaglutide induced a 15% weight loss vs 2.4% loss in the control arm. The other STEP trials confirmed similar degrees of weight loss.
Semaglutide seems to work by reducing hunger and increasing the feeling of fullness, thereby helping to cut calorie intake. Nausea, diarrhea, vomiting, and constipation were the most frequently reported adverse events and occurred in 74.2% of participants receiving semaglutide vs 47.9% of those receiving placebo. Adverse events causing discontinuation of the drug were also greater in the semaglutide arm (7.2 vs 2.8 per 100 patient-years)
On the upside, the drug is already approved for glycemic control in patients with type 2 diabetes. Loss of 15% of body weight is a both a statistically and clinically significant improvement.
Since weight loss is so integral to AF management, I see electrophysiologists using this drug.
The once weekly injection is nice feature as it will probably increase compliance.
On the downside, the trials went on for a little more than a year and obesity is a lifelong condition. Will this drug need to be continued, or once weight loss is established, will patients be able to come off the drug?
As outlined in Marlene Busko’s news coverage, cost will be a headwind. We don’t yet know what pricing will be, but given the novel nature of these findings, I’d expect Novo Nordisk will make it expensive.
Also fortunate is that there is an ongoing cardiovascular (CV) outcomes trial looking at semaglutide vs placebo in nondiabetic overweight or obese patients with CV disease. There’s also an oral formulation of semaglutide, and Novo Nordisk will study that for weight loss as well.
iPhones and Cardiac Devices
The Journal of the American Heart Association published a small study looking at the new iPhone 12’s ability to interact with implanted cardiac devices (ICDs).
Magnets interact with pacers and ICDs. A magnet placed over a pacemaker will induce asynchronous pacing and a magnet placed over an ICD will disable therapies.
Newer Apple devices use magnets to enable wireless charging.
Who hasn’t fallen asleep and found their iPhone or iPad on their chest?
The iPhone 12 Pro Max with Magsafe technology can induce magnetic fields of over 50 gauss, which is strong enough to activate magnet modes in cardiac devices.
The study had a in vivo component in which three patients (with Medtronic, Abbott, and Boston Scientific devices, respectively) who presented for generator change had an iPhone 12 placed over the device. The iPhone induced magnet reversion mode in all three devices.
In the ex-vivo component of the study, the iPhone 12 was placed over 11 devices still in the package. Selected Medtronic and Abbott devices tested were susceptible to electromagnetic interference. The Boston Scientific devices appeared to be less susceptible as no clear magnet interference was noted in the selected devices listed.
This data is similar to a case report from Heart Rhythm in which authors showed that an iPhone 12 could deactivate therapies in a Medtronic ICD. Also interesting is another Heart Rhythm report in which a Fitbit and Apple Watch wristband were able to de-activate a Medtronic ICD at 2-2.4 cm.
This issue makes the podcast because we will surely use more personal health devices and Apple promises even stronger MagSafe batteries. Word has it that iPads will soon have the stronger magnets. It seems wise to make sure our ICD patients aren’t sleeping with their i-devices. I also wonder whether device manufactures might start making the magnet reversion switch a little less sensitive.
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Cite this: Jun 11, 2021 This Week in Cardiology Podcast - Medscape - Jun 11, 2021.