Mar 5, 2021 This Week in Cardiology Podcast

John M. Mandrola, MD


March 05, 2021

Please note that the text below is not a full transcript and has not been copyedited. For more insight and commentary on these stories, subscribe to the This Week in Cardiology podcast.

In This Week’s Podcast

For the week ending March 5, 2021, John Mandrola, MD comments on the following news and features stories.


The good news continues. Cases plateaued for a bit and now have decreased further. I read a Tweet that in Connecticut, one in five people have received at least one vaccine shot.

Another underappreciated thing I learned this week is about the massive reduction in severe COVID19 after vaccination. Dr. Monica Gandhi, an infectious diseases professor at UCSF, Tweeted out a table of the phase 3 placebo-controlled vaccine trials.

The key finding was that nearly 100,000 people have received the active vaccine in these trials. Of these, guess how many had COVID significant enough to be admitted. One. Just one. Basically, vaccines turn this disease into a cold. That is amazing. Soon the pandemic will be over.

COVID and the Heart... Again

A prominent group of sports cardiologists have published yet another study looking at cardiac effects post-COVID. The first author is Mathew Martinez; and JAMA Cardiology published the cross-sectional study of nearly 800 professional athletes who underwent return-to-play screening after testing positive for COVID-19. These athletes were from the big leagues—MLS, MLB, NFL, NHL, and men’s and women’s NBA.

  • 58% had some symptoms

  • 42% no symptoms

  • Only one was admitted to hospital—for short observation.

  • Testing was performed through the teams, so this was a bit of a pragmatic real-world survey study.

  • 30 athletes or 3.8% had an abnormal finding on basic screening (15 by echocardiogram, six by electrocardiogram (ECG), five by troponin). A handful had multiple abnormalities.

  • After review of this data, 30 patients underwent cardiac magnetic resonance imaging (CMR). Five athletes or 0.6% had some evidence of inflammation, three with findings called consistent with myocarditis, two had pericarditis.

  • All five of these CMR positive cases were athletes with symptoms.

The limitations here were significant. CMR was not performed in the vast majority, thus the true incidence of abnormalities is unknown. Without a core lab, it’s hard to sort out really abnormal findings. For instance, the authors cite previous data showing that low-normal ejection fractions (EFs) are not uncommon in elite athletes. But many of the abnormal transthoracic echocardiograms in this survey were for mildly reduced EF. Was it COVID or was it the athlete’s baseline? I see this issue often. My solution is to have the athlete do a little exercise then get back on the echo table. And we all know the difficulty of interpreting ECGs in elite athletes. There was also significant variation in time to testing; some athletes may have recovered by the time of testing. But this is still pretty strong real-world data.

Take homes:

  • Young athletes do very well with COVID; 800 cases and no severe COVID. In the authors’ own words: “we observed only rare cases of athletes having potential cardiac involvement.”

  • The ECG underperformed. The notion of adding a routine ECG in athletes is fraught. I see this often as well—normative findings in athletes are not well recognized by most cardiologists.

  • CMR should only be used as a downstream test after careful consideration on a case-by-case basis.

  • As with all other post-COVID cardiac studies, this study lacks a comparator group. What would we find if we did similar testing after febrile illnesses due to non-COVID respiratory viruses? My hunch is it would look similar.

Clipping Mitral and Tricuspid Valves

A group at the University of Cologne, first author, Maria Korber, published a research letter in JACC-Intervention on post-op delirium after percutaneous repair of the mitral and tricuspid valve.

This is a small study but an important one. Here is why: when you read big trials in cardiology, you are getting data from a highly selected group of patients. Nearly all trials, especially those sponsored by industry, are enriched with patients most likely to benefit. This is not nefarious; it is a way to identify a group that can benefit from the intervention. The best example, I think, is that most cardiology trials exclude patients with severe kidney disease. They do this because bad kidney represents a strong competing cause of bad outcomes, such as death.

Another example of how important patient selection is: look at the difference between MITRA-FR and COAPT trials of Mitra-Clip. In Mitra-FR, there was no benefit; in COAPT, the benefit was huge. When you look at the patient characteristics, it is hard to tell a difference. Proponents of the Mitra-Clip say there were differences in the size of the left ventricle relative to the severity of mitral regurgitation, but these are determined by ultrasound shadows and measured in millimeters.

My point is not to reargue the two divergent trials, only to point out the crucial nature of patient selection in using advanced technology—especially in older patients. I believe this is the core challenge in clinical cardiology: most patients we intervene on outside of trials are much sicker than those in the trials. Mitral and tricuspid disease that is considered for percutaneous repair is by definition a disease of the aged and infirmed. Otherwise, they would have open surgical repair. Brain disease is a common co-morbid condition. And post-op delirium is an underrecognized severe complication of any intervention.

The German team studied 177 patients at their center who had mitral or tricuspid intervention. They systematically studied delirium using an accepted scoring system called the CAM-ICU score.

  • Post-op delirium (POD) occurred in 9% of patients and no baseline characteristics predominated in those with or without POD.

  • The procedure was just as “technically” successful in those with and without POD.

  • Hospital stays were longer in patients with POD.

  • Those with POD had a much higher rate of death at 6 months. The point estimate of the hazard ratio for death was 3.84—so nearly 4 times higher rate of death. The confidence interval ranged from a 41% higher rate of death to a 10-fold increase.

I laud the authors and the journal for publishing this data.

Patrice Wendling has great news coverage of it. She quotes Dr. David Wood from Univ of British Columbia who said delirium was an important thing to study and emphasized the notion that iterations of the procedure to more minimally invasive will likely reduce the incidence of delirium.

I agree that moving away from 4-hour procedures under general anesthesia will improve things. But I also think cardiologists must always remember that mitral and tricuspid regurgitation are often just one of the many causes of morbidity in older people. Our challenge is not whether we can clip a valve but whether we ought too. Studies like this help remind us of this core challenge.

Atrial Fibrillation Screening

Whenever I hear about a randomized controlled trial in the screening space, I get excited. The name of the trial is SCREEN-AF. It’s led by Canadian investigators, first author, David Gladstone, MD, and JAMA Cardiology published the paper.

SCREEN-AF studied the question of whether screening for AF with a 2-week patch ECG placed twice at 3-month intervals would be better than routine care—basically no screening. Smartly, they enrolled only patients over the age of 75 who had hypertension. Thus, they gave themselves a good shot of finding AF, as age and hypertension are two of the many conditions associated with AF.

The primary endpoint of the study was detected AF; secondary endpoint was prescriptions for oral anticoagulants. Within the active screening arm was a substudy comparing the patch to a twice-daily blood pressure and heart rate (BP/HR) recording from a blood pressure machine capable of indicating an irregular pulse.

In all, 856 patients were enrolled from 48 primary care practices; mean age 80 years; CHADSVASC score ≈ 4. AF was detected in 23 patients or 5.3% of the screened group vs 0.5% of the routine care group. Obviously, an odds ratio of 11 is statistically significant. The absolute risk difference is 4.8% or a number needed to screen (NNS) of 21.

Of those with AF detected, the median time in AF was 6 hours and median duration for the longest AF was 5.7 hours. Only 3 of the more than 400 patients screened with a patch had more than 24 hours of AF. Oral anticoagulation was started in 15 of 20 patients with patch-detected AF.

In the substudy comparing the patch screening vs twice-daily BP/HR measures found that the BP/HR device was clearly inferior, with a sensitivity (true positive rate) of 35.0% and a specificity (true negative rate) of 81.0%.

Here is another chance to use Bayes.

  • The prior is the 5% prevalence of AF in the screened group.

  • The likelihood ratio (LR) is the sensitivity divided by one minus specificity (true positivity over false positivity) or 35%/19% = 1.8.

  • This is how much the BP/HR test updates your chances of having AF if positive.

  • Thus, the posterior probability of having AF after a positive BP/HR test is the prevalence of AF (0.05) x LR (1.8) ≈ 9%.

Thus, that is a terrible test. In this study, the incidence of AF was 5% but if you had a positive irregular HR signal on the BP cuff it only went up to 9%.

This appears to be a well-conducted trial. It is in line with every AF screening study I have seen—if you look for AF with any device, you will find more AF, and this will lead to more prescriptions for oral anticoagulants. But that is not the endpoint we care about. We care about making people live longer or feel better. That means reducing stroke or death. This study doesn’t come close to knowing that. In fact, two participants had ischemic strokes, and both were in the screened group.

But even if we assume that treating patients with short-duration AF lowers the stroke rate, let’s do a calculation on how much we would need to screen to reduce stroke. The NNS to pick up one case of AF in this study was about 21. If we are generous, the absolute risk reduction for oral anticoagulation in this high-risk group is about 4%, or a number needed to treat (NNT) of 25. So, the NNS to prevent one stroke (with expensive medical grade ECG patches) was 21 x 25 ≈ 525. Theoretically, and with all the limitations of NNT, that means 524/525 patients exposed to this type of screening get no benefit. And this does not include the risks of downstream testing from the false-positives and other incidental arrhythmias, such as asymptomatic bradycardia or premature ventricular contractions. Nor does it include the increased risks of bleeding from the oral anticoagulants.

These monitors are very useful as diagnostic devices, which, of course, is different from screening. We use them for diagnostic purposes on people who have a problem and have sought our help. People in this screening trial were asymptomatic.

The authors write, “Compared with implanted cardiac monitors, wearable ECG devices are noninvasive, less costly, more accessible, can be self-applied by patients at home, and have fewer false-positive results.”

They are probably all of those things, but less costly is relative. If your insurance does not cover these patches, they are very expensive. And even if they are covered, we all pay for costly low-value healthcare in the form of higher premiums. When the evidence shows that screening for AF cost-effectively reduces an important outcome like stroke or overall mortality, I will become a huge advocate. We are not there yet.

Final Comments on Social Media

If you are a doctor and pay attention to social media, recent news could be considered depressing. JAMA got into trouble with a podcast about structural racism; a couple of prominent doctors at Oregon Health and Science University are embroiled in a sexual harassment suit—which will be settled slowly with due process.

But it always helps to remember that, if you chose this profession, you did good.


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